{"id": "PMID:21", "title": "[Biochemical studies on camomile components/III. In vitro studies about the antipeptic activity of (--)-alpha-bisabolol (author's transl)].", "content": "(--)-alpha-Bisabolol has a primary antipeptic action depending on dosage, which is not caused by an alteration of the pH-value. The proteolytic activity of pepsin is reduced by 50 percent through addition of bisabolol in the ratio of 1/0.5. The antipeptic action of bisabolol only occurs in case of direct contact. In case of a previous contact with the substrate, the inhibiting effect is lost.", "contents": "[Biochemical studies on camomile components/III. In vitro studies about the antipeptic activity of (--)-alpha-bisabolol (author's transl)]. (--)-alpha-Bisabolol has a primary antipeptic action depending on dosage, which is not caused by an alteration of the pH-value. The proteolytic activity of pepsin is reduced by 50 percent through addition of bisabolol in the ratio of 1/0.5. The antipeptic action of bisabolol only occurs in case of direct contact. In case of a previous contact with the substrate, the inhibiting effect is lost."}
{"id": "PMID:22", "title": "[Demonstration of tumor inhibiting properties of a strongly immunostimulating low-molecular weight substance. Comparative studies with ifosfamide on the immuno-labile DS carcinosarcoma. Stimulation of the autoimmune activity for approx. 20 days by BA 1, a N-(2-cyanoethylene)-urea. Novel prophylactic possibilities].", "content": "A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising.", "contents": "[Demonstration of tumor inhibiting properties of a strongly immunostimulating low-molecular weight substance. Comparative studies with ifosfamide on the immuno-labile DS carcinosarcoma. Stimulation of the autoimmune activity for approx. 20 days by BA 1, a N-(2-cyanoethylene)-urea. Novel prophylactic possibilities]. A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising."}
{"id": "PMID:23", "title": "Effect of etafenone on total and regional myocardial blood flow.", "content": "The distribution of blood flow to the subendocardial, medium and subepicardial layers of the left ventricular free wall was studied in anaesthetized dogs under normoxic (A), hypoxic (B) conditions and under pharmacologically induced (etafenone) coronary vasodilation (C). Regional myocardial blood flow was determined by means of the particle distribution method. In normoxia a transmural gradient of flow was observed, with the subendocardial layers receiving a significantly higher flow rate compared with the subepicardial layers. In hypoxia induced vasodilation this transmural gradient of flow was persistent. In contrast a marked redistribution of regional flow was observed under pharmacologically induced vasodilation. The transmural gradient decreased. In contrast to some findings these experiments demonstrate that a considerable vasodilatory capacity exists in all layers of the myocardium and can be utilized by drugs. The differences observed for the intramural distribution pattern of flow under hypoxia and drug induced vasodilation support the hypothesis that this pattern reflects corresponding gradients of regional myocardial metabolism.", "contents": "Effect of etafenone on total and regional myocardial blood flow. The distribution of blood flow to the subendocardial, medium and subepicardial layers of the left ventricular free wall was studied in anaesthetized dogs under normoxic (A), hypoxic (B) conditions and under pharmacologically induced (etafenone) coronary vasodilation (C). Regional myocardial blood flow was determined by means of the particle distribution method. In normoxia a transmural gradient of flow was observed, with the subendocardial layers receiving a significantly higher flow rate compared with the subepicardial layers. In hypoxia induced vasodilation this transmural gradient of flow was persistent. In contrast a marked redistribution of regional flow was observed under pharmacologically induced vasodilation. The transmural gradient decreased. In contrast to some findings these experiments demonstrate that a considerable vasodilatory capacity exists in all layers of the myocardium and can be utilized by drugs. The differences observed for the intramural distribution pattern of flow under hypoxia and drug induced vasodilation support the hypothesis that this pattern reflects corresponding gradients of regional myocardial metabolism."}
{"id": "PMID:24", "title": "Influence of a new virostatic compound on the induction of enzymes in rat liver.", "content": "The virostatic compound N,N-diethyl-4-[2-(2-oxo-3-tetradecyl-1-imidazolidinyl)-ethyl]-1-piperazinecarboxamide-hydrochloride (5531) was analyzed as to its effect on the induction of tryptophan-pyrrolase and tyrosineaminotransferase in rat liver. 1. The basic activity of the enzymes was not influenced by the substance either in normal or in adrenalectomized animals. 2. The induction of the enzymes by cortisone increased in the presence of the compound whereas the substrate induction remained unchanged. 3. The induction of tyrosine-aminotransferase by dexamethasonephosphate in tissue culture is inhibited if the dose of compound 5531 is higher than 5 mug/ml.", "contents": "Influence of a new virostatic compound on the induction of enzymes in rat liver. The virostatic compound N,N-diethyl-4-[2-(2-oxo-3-tetradecyl-1-imidazolidinyl)-ethyl]-1-piperazinecarboxamide-hydrochloride (5531) was analyzed as to its effect on the induction of tryptophan-pyrrolase and tyrosineaminotransferase in rat liver. 1. The basic activity of the enzymes was not influenced by the substance either in normal or in adrenalectomized animals. 2. The induction of the enzymes by cortisone increased in the presence of the compound whereas the substrate induction remained unchanged. 3. The induction of tyrosine-aminotransferase by dexamethasonephosphate in tissue culture is inhibited if the dose of compound 5531 is higher than 5 mug/ml."}
{"id": "PMID:25", "title": "Pharmacological properties of new neuroleptic compounds.", "content": "RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.", "contents": "Pharmacological properties of new neuroleptic compounds. RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level."}
{"id": "PMID:26", "title": "[Studies on the action of an anticholinergic agent in combination with a tranquilizer on gastric juice secretion in man].", "content": "A double-blind study with intra-individual comparisons was carried out to investigate the effects of 15 mg of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH-tropanium bromide(+/-)-tropate (Sch 1000), 15 mg Sch 1000 + 10 mg oxazepam, 10 mg oxazepam and placebo with oral administration in randomized sequence on gastric juice volume, amount of acid, concentration and pH values in 12 healthy volunteers. The secretion parameters were measured during a 1-h basal period and a 2-h stimulation period. The gastric juice was obtained in 15 min portions via stomach tube. Stimulation was effected by 1 mug/kg/h pentagastrin via drip infusion. The Friedman test was used for the comparative statistical evaluation, and individual comparisons were carried out by means of the Wilcoxon test (pair-differences rank). The results show that Sch 1000 and Sch 1000 + oxazepam were equal in effect on basal and stimulated secretion volume. As compared with placebo, it was not possible to establish an effect on secretion volume for oxazepam alone. Sch 1000 and Sch 1000 + oxazepam were found to be equipotent in reducing the amount of basal acid, while oxazepam reduced this quantity only during the first 30 min of basal secretion. None of the three active preparations was capable of inhibiting the stimulated acid, although both Sch 1000 preparations produced a clear trend towards lowered mean values. During the basal secretion period, all three test preparations had an inhibiting action on acid concentration, but none of them had a significant effect during the stimulation period. The pH value was savely increased only by Sch 1000 and Sch 1000 + oxazepam, and this even only during the basal period. The results are discussed.", "contents": "[Studies on the action of an anticholinergic agent in combination with a tranquilizer on gastric juice secretion in man]. A double-blind study with intra-individual comparisons was carried out to investigate the effects of 15 mg of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH-tropanium bromide(+/-)-tropate (Sch 1000), 15 mg Sch 1000 + 10 mg oxazepam, 10 mg oxazepam and placebo with oral administration in randomized sequence on gastric juice volume, amount of acid, concentration and pH values in 12 healthy volunteers. The secretion parameters were measured during a 1-h basal period and a 2-h stimulation period. The gastric juice was obtained in 15 min portions via stomach tube. Stimulation was effected by 1 mug/kg/h pentagastrin via drip infusion. The Friedman test was used for the comparative statistical evaluation, and individual comparisons were carried out by means of the Wilcoxon test (pair-differences rank). The results show that Sch 1000 and Sch 1000 + oxazepam were equal in effect on basal and stimulated secretion volume. As compared with placebo, it was not possible to establish an effect on secretion volume for oxazepam alone. Sch 1000 and Sch 1000 + oxazepam were found to be equipotent in reducing the amount of basal acid, while oxazepam reduced this quantity only during the first 30 min of basal secretion. None of the three active preparations was capable of inhibiting the stimulated acid, although both Sch 1000 preparations produced a clear trend towards lowered mean values. During the basal secretion period, all three test preparations had an inhibiting action on acid concentration, but none of them had a significant effect during the stimulation period. The pH value was savely increased only by Sch 1000 and Sch 1000 + oxazepam, and this even only during the basal period. The results are discussed."}
{"id": "PMID:30", "title": "Lysosomal hydrolases of the epidermis. I. Glycosidases.", "content": "Seven distinct glycosidases (EC 3.2) have been characterized in guinea-pig epidermis. Their properties indicate them to be of lysosomal origin. The 'profile' of the epidermal glycosidases is significantly different from that reported for whole skin, the activities of beta-galactosidase and beta-acetylglucosaminidase being very high and those of the remaining enzymes relatively low in epidermis.", "contents": "Lysosomal hydrolases of the epidermis. I. Glycosidases. Seven distinct glycosidases (EC 3.2) have been characterized in guinea-pig epidermis. Their properties indicate them to be of lysosomal origin. The 'profile' of the epidermal glycosidases is significantly different from that reported for whole skin, the activities of beta-galactosidase and beta-acetylglucosaminidase being very high and those of the remaining enzymes relatively low in epidermis."}
{"id": "PMID:31", "title": "Lysosomal hydrolases of the epidermis. 2. Ester hydrolases.", "content": "Five distinct ester hydrolases (EC 3-1) have been characterized in guinea-pig epidermis. These are carboxylic esterase, acid phosphatase, pyrophosphatase, and arylsulphatase A and B. Their properties are consistent with those of lysosomal enzymes.", "contents": "Lysosomal hydrolases of the epidermis. 2. Ester hydrolases. Five distinct ester hydrolases (EC 3-1) have been characterized in guinea-pig epidermis. These are carboxylic esterase, acid phosphatase, pyrophosphatase, and arylsulphatase A and B. Their properties are consistent with those of lysosomal enzymes."}
{"id": "PMID:32", "title": "A serum haemagglutinating property dependent upon polycarboxyl groups.", "content": "A serum agglutinin reactive with red cells in the presence of polycarboxyl groups is reported. It is likely that this represents an additional example of the type of agglutinin previously described as agglutinating red cells in the absence of ionized calcium. Experimental evidence is presented indicating that it is free polycarboxyl groups that potentiate agglutination and that any metal ion, such as calcium, capable of chelating with these groups will prove to be inhibitory.", "contents": "A serum haemagglutinating property dependent upon polycarboxyl groups. A serum agglutinin reactive with red cells in the presence of polycarboxyl groups is reported. It is likely that this represents an additional example of the type of agglutinin previously described as agglutinating red cells in the absence of ionized calcium. Experimental evidence is presented indicating that it is free polycarboxyl groups that potentiate agglutination and that any metal ion, such as calcium, capable of chelating with these groups will prove to be inhibitory."}
{"id": "PMID:33", "title": "Effect of human erythrocyte stromata on complement activation.", "content": "Stroma from either normal or PNH-like red cells is capable of inhibiting, to some extent, lysis in the sucrose test and enhancing lysis in the acidified-serum test. The same opposing effects are displayed by the exclusion peaks from Sephadex G-200 obtained from each stroma preparation, suggesting that the same factor could be responsible for both activities. Stromata and peaks also induce lysis of PNH-like cells in unacidified serum, indicating activation of complement through the alternate pathway. This is confirmed by immunoelectrophoretic observation. When serum previously activated through the alternate pathway is used in the sucrose test the amount of lysis is markedly reduced. This would indicate that the classical pathway activation can be controlled by the alternate pathway. The possible clinical significance of these factors in determining the haemolytic crisis in PNH patients is discussed.", "contents": "Effect of human erythrocyte stromata on complement activation. Stroma from either normal or PNH-like red cells is capable of inhibiting, to some extent, lysis in the sucrose test and enhancing lysis in the acidified-serum test. The same opposing effects are displayed by the exclusion peaks from Sephadex G-200 obtained from each stroma preparation, suggesting that the same factor could be responsible for both activities. Stromata and peaks also induce lysis of PNH-like cells in unacidified serum, indicating activation of complement through the alternate pathway. This is confirmed by immunoelectrophoretic observation. When serum previously activated through the alternate pathway is used in the sucrose test the amount of lysis is markedly reduced. This would indicate that the classical pathway activation can be controlled by the alternate pathway. The possible clinical significance of these factors in determining the haemolytic crisis in PNH patients is discussed."}
{"id": "PMID:35", "title": "The effect of o-salicylate upon pentose phosphate pathway activity in normal and G6PD-deficient red cells.", "content": "The effect of the major metabolite of aspirin, namely salicylic acid, upon the pentose phosphate pathway (PPP) of normal and G6PD-deficient red cells has been studied. Salicylic acid was shown to inhibit this pathway in proportion to the amount present. At any concentration of this substance there was greater inhibition of the PPP in G6PD-deficient than in normal red cells.", "contents": "The effect of o-salicylate upon pentose phosphate pathway activity in normal and G6PD-deficient red cells. The effect of the major metabolite of aspirin, namely salicylic acid, upon the pentose phosphate pathway (PPP) of normal and G6PD-deficient red cells has been studied. Salicylic acid was shown to inhibit this pathway in proportion to the amount present. At any concentration of this substance there was greater inhibition of the PPP in G6PD-deficient than in normal red cells."}
{"id": "PMID:36", "title": "The effects of processing of barley-based supplements on rumen pH, rate of digestion of voluntary intake of dried grass in sheep.", "content": "1. In one experiment the effect on rumen pH of feeding with restricted amounts of whole or pelleted barley was studied. With whole barley there was little variation in rumen pH associated with feeding time, but with pelleted barley the pH decreased from about 7-0 before feeding to about 5-3, 2--3 h after feeding. 2. The rate of disappearance of dried grass during incubation in the rumens of sheep receiving either whole or pelleted barley was studied in a second experiment. After 24 h incubation only 423 mg/g incubated had disappeared in the rumen of sheep receiving pelleted barley while 625 mg/g incubated had disappeared when it was incubated in the rumen of sheep receiving whole barley. 3. The voluntary intake of dried grass of lambs was studied in a third experiment when they received supplements of either 25 or 50 g whole or pelleted barley/kg live weight 0-75. At the high level, pelleted barley reduced intake of dried grass by 534 g/kg but whole barley reduced it by only 352 g/kg. The digestibility of acid-detergent fibre was reduced more by pelleted barley than by whole barley but there was a tendency for a small increase in digestibility of the barley due to processing. 4. The implications of these findings on supplementation of roughages with cereals are discussed.", "contents": "The effects of processing of barley-based supplements on rumen pH, rate of digestion of voluntary intake of dried grass in sheep. 1. In one experiment the effect on rumen pH of feeding with restricted amounts of whole or pelleted barley was studied. With whole barley there was little variation in rumen pH associated with feeding time, but with pelleted barley the pH decreased from about 7-0 before feeding to about 5-3, 2--3 h after feeding. 2. The rate of disappearance of dried grass during incubation in the rumens of sheep receiving either whole or pelleted barley was studied in a second experiment. After 24 h incubation only 423 mg/g incubated had disappeared in the rumen of sheep receiving pelleted barley while 625 mg/g incubated had disappeared when it was incubated in the rumen of sheep receiving whole barley. 3. The voluntary intake of dried grass of lambs was studied in a third experiment when they received supplements of either 25 or 50 g whole or pelleted barley/kg live weight 0-75. At the high level, pelleted barley reduced intake of dried grass by 534 g/kg but whole barley reduced it by only 352 g/kg. The digestibility of acid-detergent fibre was reduced more by pelleted barley than by whole barley but there was a tendency for a small increase in digestibility of the barley due to processing. 4. The implications of these findings on supplementation of roughages with cereals are discussed."}
{"id": "PMID:37", "title": "Poly(8-aminoguanylic acid): formation of ordered self-structures and interaction with poly(cytidylic acid).", "content": "Poly(8-aminoguanylic acid) has in neutral solution a novel ordered structure of high stability. The 8-amino group permits formation of three hydrogen bonds between two residues along the \"top\", or long axis, of the purines. The usual hydrogen bonding protons and Watson-Crick pairing sites are not involved in the association. The bonding scheme has a twofold rotation axis and is hemiprotonated at N(7). Poly(8NH2G) is converted by alkaline titration (pK = 9.7) to a quite different ordered structure, which is the favored form over the range approximately pH 10-11. The bonding scheme appears to be composed of a planar, tetrameric array of guanine residues, in which the 8-amino group does not participate in interbase hydrogen bonding. Poly (8NH2G) does not interact with poly(C) in neutral solution because of the high stability of the hemiprotonated G-G self-structure. Titration to the alkaline plateau, however, permits ready formation of a two-stranded Watson-Crick helix. In contrast to the monomer 8NH2GMP, poly(8NH2G) does not form a triple helix with poly(C) under any conditions. The properties of the ordered structures are interpreted in terms of a strong tendency of the 8-amino group to form a third interbase hydrogen bond, when this possibility is not prevented by high pH.", "contents": "Poly(8-aminoguanylic acid): formation of ordered self-structures and interaction with poly(cytidylic acid). Poly(8-aminoguanylic acid) has in neutral solution a novel ordered structure of high stability. The 8-amino group permits formation of three hydrogen bonds between two residues along the \"top\", or long axis, of the purines. The usual hydrogen bonding protons and Watson-Crick pairing sites are not involved in the association. The bonding scheme has a twofold rotation axis and is hemiprotonated at N(7). Poly(8NH2G) is converted by alkaline titration (pK = 9.7) to a quite different ordered structure, which is the favored form over the range approximately pH 10-11. The bonding scheme appears to be composed of a planar, tetrameric array of guanine residues, in which the 8-amino group does not participate in interbase hydrogen bonding. Poly (8NH2G) does not interact with poly(C) in neutral solution because of the high stability of the hemiprotonated G-G self-structure. Titration to the alkaline plateau, however, permits ready formation of a two-stranded Watson-Crick helix. In contrast to the monomer 8NH2GMP, poly(8NH2G) does not form a triple helix with poly(C) under any conditions. The properties of the ordered structures are interpreted in terms of a strong tendency of the 8-amino group to form a third interbase hydrogen bond, when this possibility is not prevented by high pH."}
{"id": "PMID:38", "title": "Effect of pH on substrate and inhibitor kinetic constants of human liver alanine aminopeptidase. Evidence for two ionizable active center groups.", "content": "The presence of at least two ionizable active center groups has been detected by a study of the effect of pH upon catalysis of hydrolysis of L-alanyl-beta-naphthylamide by human liver alanine aminopeptidase and upon the inhibition of hydrolysis by inhibitors and substrate analogs. Octanoic acid, octylamine, and peptide inhibitors have been found to be competitive inhibitors and are therefore thought to bind the active center. L-Phe was previously shown to bind the active center since it was found to be a competitive inhibitor of the hydrolysis of tripeptide substrates (Garner, C. W., and Behal, F. J. (1975), Biochemistry 14, 3208). A plot of pKm vs. pH for the substrate L-Ala-beta-naphthylamide showed that binding decreased below pH 5.9 and above 7.5, the points at which the theoretical curve undergoes an integral change in slope. These points are interpreted as the pKa either of substrate ionizable groups or binding-dependent enzyme active center groups. Similar plots of pKm vs. pH for L-alanyl-p-nitroanilide (as substrate) and pKi vs. pH for L-Leu-L-Leu-L-Leu and D-Leu-L-Tyr (as inhibitors) gave pairs fo pKa values of 5.8 and 7.4, 6.0 and 7.5, and 5.7 and 7.5, respectively. All the above substrates (and D-Leu-L-Tyr) have pKa values near 7.5; therefore, the binding-dependent group with a pKa value near 7.5 is possibly this substrate group. Similar plots of pKi vs. pH for the inhibitors L-Phe, L-Met, L-Leu, octylamine, and octanoic acid had only one bending point at 7.7, 7.6, 7.4, 6.3, and 5.9, respectively. Amino acid inhibitors, octylamine, and octanoic acid have no groups with pKa values between 5 and 9. These data indicate that there are two active center ionizable groups with pKa values of approximately 6.0 and 7.5 which are involved in substrate binding or inhibitory amino acid binding but not in catalysis since Vmax was constant at all pH values tested.", "contents": "Effect of pH on substrate and inhibitor kinetic constants of human liver alanine aminopeptidase. Evidence for two ionizable active center groups. The presence of at least two ionizable active center groups has been detected by a study of the effect of pH upon catalysis of hydrolysis of L-alanyl-beta-naphthylamide by human liver alanine aminopeptidase and upon the inhibition of hydrolysis by inhibitors and substrate analogs. Octanoic acid, octylamine, and peptide inhibitors have been found to be competitive inhibitors and are therefore thought to bind the active center. L-Phe was previously shown to bind the active center since it was found to be a competitive inhibitor of the hydrolysis of tripeptide substrates (Garner, C. W., and Behal, F. J. (1975), Biochemistry 14, 3208). A plot of pKm vs. pH for the substrate L-Ala-beta-naphthylamide showed that binding decreased below pH 5.9 and above 7.5, the points at which the theoretical curve undergoes an integral change in slope. These points are interpreted as the pKa either of substrate ionizable groups or binding-dependent enzyme active center groups. Similar plots of pKm vs. pH for L-alanyl-p-nitroanilide (as substrate) and pKi vs. pH for L-Leu-L-Leu-L-Leu and D-Leu-L-Tyr (as inhibitors) gave pairs fo pKa values of 5.8 and 7.4, 6.0 and 7.5, and 5.7 and 7.5, respectively. All the above substrates (and D-Leu-L-Tyr) have pKa values near 7.5; therefore, the binding-dependent group with a pKa value near 7.5 is possibly this substrate group. Similar plots of pKi vs. pH for the inhibitors L-Phe, L-Met, L-Leu, octylamine, and octanoic acid had only one bending point at 7.7, 7.6, 7.4, 6.3, and 5.9, respectively. Amino acid inhibitors, octylamine, and octanoic acid have no groups with pKa values between 5 and 9. These data indicate that there are two active center ionizable groups with pKa values of approximately 6.0 and 7.5 which are involved in substrate binding or inhibitory amino acid binding but not in catalysis since Vmax was constant at all pH values tested."}
{"id": "PMID:39", "title": "Formation of transient complexes in the glutamate dehydrogenase catalyzed reaction.", "content": "The reaction of glutamate dehydrogenase and glutamate (gl) with NAD+ and NADP+ has been studied with stopped-flow techniques. The enzyme was in all experiments present in excess of the coenzyme. The results indicate that the ternary complex (E-NAD(P)H-kg) is present as an intermediate in the formation of the stable complex (E-NAD(P)H-gl). The identification of the complexes is based on their absorption spectra. The binding of the coenzyme to (E-gl) is the rate-limiting step in the formation of (E-NAD(P)H-kg) while the dissociation of alpha-ketoglutarate (kg) from this complex is the rate-limiting step in the formation of (E-NAD(P)H-gl). The Km for glutamate was 20-25 mM in the first reaction and 3 mM in the formation of the stable complex. The Km values were independent of the coenzyme. The reaction rates with NAD+ were approximately 50% greater than those with NADP+. Furthermore, high glutamate concentration inhibited the formation of (E-NADH-kg) while no substrate inhibition was found with NADP+ as coenzyme. ADP enhanced while GTP reduced the rate of (E-NAD(P)H-gl) formation. The rate of formation of (E-NAD(P)H-kg) was inhibited by ADP, while it increased at high glutamate concentration when small amounts of GTP were added. The results show that the higher activity found with NAD+ compared to NADP+ under steady-state assay conditions do not necessarily involve binding of NAD+ to the ADP activating site of the enzyme. Moreover, the substrate inhibition found at high glutamate concentration under steady-state assay condition is not due to the formation of (E-NAD(P)H-gl) as this complex is formed with Km of 3 mM glutamate, and the substrate inhibition is only significant at 20-30 times this concentration.", "contents": "Formation of transient complexes in the glutamate dehydrogenase catalyzed reaction. The reaction of glutamate dehydrogenase and glutamate (gl) with NAD+ and NADP+ has been studied with stopped-flow techniques. The enzyme was in all experiments present in excess of the coenzyme. The results indicate that the ternary complex (E-NAD(P)H-kg) is present as an intermediate in the formation of the stable complex (E-NAD(P)H-gl). The identification of the complexes is based on their absorption spectra. The binding of the coenzyme to (E-gl) is the rate-limiting step in the formation of (E-NAD(P)H-kg) while the dissociation of alpha-ketoglutarate (kg) from this complex is the rate-limiting step in the formation of (E-NAD(P)H-gl). The Km for glutamate was 20-25 mM in the first reaction and 3 mM in the formation of the stable complex. The Km values were independent of the coenzyme. The reaction rates with NAD+ were approximately 50% greater than those with NADP+. Furthermore, high glutamate concentration inhibited the formation of (E-NADH-kg) while no substrate inhibition was found with NADP+ as coenzyme. ADP enhanced while GTP reduced the rate of (E-NAD(P)H-gl) formation. The rate of formation of (E-NAD(P)H-kg) was inhibited by ADP, while it increased at high glutamate concentration when small amounts of GTP were added. The results show that the higher activity found with NAD+ compared to NADP+ under steady-state assay conditions do not necessarily involve binding of NAD+ to the ADP activating site of the enzyme. Moreover, the substrate inhibition found at high glutamate concentration under steady-state assay condition is not due to the formation of (E-NAD(P)H-gl) as this complex is formed with Km of 3 mM glutamate, and the substrate inhibition is only significant at 20-30 times this concentration."}
{"id": "PMID:40", "title": "Human brain and placental choline acetyltransferase: purification and properties.", "content": "Choline acetyltransferase (EC 2.3.1.6) catalyzes the biosynthesis of acetylcholine according to the following chemical equation: acetyl-CoA + choline in equilibrium to acetylcholine + CoA. In addition to nervous tissue, primate placenta is the only other animal source which contains appreciable acetylcholine and its biosynthetic enzyme. Human brain caudate nucleus and human placental choline acetyltransferase were purified to electrophoretic homogeneity using ion-exchange and blue dextran-Sepharose affinity chromatography. The molecular weights determined by Sephadex G-150 gel filtration and sodium dodecyl sulfate gel electrophoresis are 67000 plus or minus 3000. N-Ethylmaleimide, p-chloromercuribenzoate, and dithiobis(2-nitrobenzoic acid) inhibit the enzyme. Dithiothreitol reverses the inhibition produced by the latter two reagents. The pKa of the group associated with N-ethylmaleimide inhibition is 8.6 plus or minus 0.3. A chemically competent acetyl-thioenzyme is isolable by Sephadex gel filtration. The enzymes from the brain and placenta are thus far physically and biochemically indistinguishable.", "contents": "Human brain and placental choline acetyltransferase: purification and properties. Choline acetyltransferase (EC 2.3.1.6) catalyzes the biosynthesis of acetylcholine according to the following chemical equation: acetyl-CoA + choline in equilibrium to acetylcholine + CoA. In addition to nervous tissue, primate placenta is the only other animal source which contains appreciable acetylcholine and its biosynthetic enzyme. Human brain caudate nucleus and human placental choline acetyltransferase were purified to electrophoretic homogeneity using ion-exchange and blue dextran-Sepharose affinity chromatography. The molecular weights determined by Sephadex G-150 gel filtration and sodium dodecyl sulfate gel electrophoresis are 67000 plus or minus 3000. N-Ethylmaleimide, p-chloromercuribenzoate, and dithiobis(2-nitrobenzoic acid) inhibit the enzyme. Dithiothreitol reverses the inhibition produced by the latter two reagents. The pKa of the group associated with N-ethylmaleimide inhibition is 8.6 plus or minus 0.3. A chemically competent acetyl-thioenzyme is isolable by Sephadex gel filtration. The enzymes from the brain and placenta are thus far physically and biochemically indistinguishable."}
{"id": "PMID:41", "title": "Stabilization of the globular structure of ferricytochrome c by chloride in acidic solvents.", "content": "Increasing concentrations of chloride were found to increase the resolution between two visible absorbance spectral transitions associated with acidification of ferricytochrome c. Analysis of a variety of spectral and viscosity measurements indicates that protonation of a single group having an apparent pK of 2.1 +/- 0.2 and an intrinsic pK of about 5.3 displaces the methionine ligand without significantly perturbing the native globular conformation. Analysis of methylated ferricytochrome c suggests that protonation of a carboxylate ion, most likely a heme propionate residue, is responsible for displacement of the methionine ligand. Addition of a proton to a second group having an apparent pK of 1.2 +/- 0.1 displaces the histidine ligand and unfolds the protein from a globular conformation into a random coil. It is most likely that the second protonation occurs on the imidazole ring of the histidine ligand itself. Chloride is proposed to perturb these transitions by ligation in the fifth coordination position of the heme ion. Such ligation stabilizes a globular conformation of ferricytochrome c at pH 0.0 and 25 degrees.", "contents": "Stabilization of the globular structure of ferricytochrome c by chloride in acidic solvents. Increasing concentrations of chloride were found to increase the resolution between two visible absorbance spectral transitions associated with acidification of ferricytochrome c. Analysis of a variety of spectral and viscosity measurements indicates that protonation of a single group having an apparent pK of 2.1 +/- 0.2 and an intrinsic pK of about 5.3 displaces the methionine ligand without significantly perturbing the native globular conformation. Analysis of methylated ferricytochrome c suggests that protonation of a carboxylate ion, most likely a heme propionate residue, is responsible for displacement of the methionine ligand. Addition of a proton to a second group having an apparent pK of 1.2 +/- 0.1 displaces the histidine ligand and unfolds the protein from a globular conformation into a random coil. It is most likely that the second protonation occurs on the imidazole ring of the histidine ligand itself. Chloride is proposed to perturb these transitions by ligation in the fifth coordination position of the heme ion. Such ligation stabilizes a globular conformation of ferricytochrome c at pH 0.0 and 25 degrees."}
{"id": "PMID:42", "title": "A competitive labeling method for the determination of the chemical properties of solitary functional groups in proteins.", "content": "The properties of the functional groups in a protein can be used as built-in-probes of the structure of the protein. We have developed a general procedure whereby the ionization constant and chemical reactivity of solitary functional groups in proteins may be determined. The method may be applied to the side chain of histidine, tyrosine, lysine, and cysteine, as well as to the amino terminus of the protein. The method, which is an extension of the competitive labeling technique using [3H]- and [14C]1-fluoro-2,4-dinitrobenzene (N2ph-F) in a double-labeling procedure, is rapid and sensitive. Advantage is taken of the fact that after acid hydrolysis of a dinitrophenylated protein, a derivative is obtained which must be derived from a unique position in the protein. The method has been applied to the solitary histidine residue of lysozyme, alpha-lytic protease, and Streptomyces griseus (S.G.) trypsin, as well as to the amino terminus of the latter protein. The following parameters were obtained for reaction with N2ph-F at 20 degrees C in 0.1 N KCl: the histidine of hen egg-white lysozyme, pKa of 6.4 and second-order velocity constant of 0.188 M-1 min-1; the histidine of alpha-lytic protease, pKa of 6.5 and second-order velocity constant of 0.0235 M-1 min-1; the histidine of S.G. trypsin, pKa of 6.5 and second-order velocity constant of 0.0328 M-1 min-1; the valyl amino terminus of S.G. trypsin, pKa of 8.1 and second-order velocity constant of 0.403 M-1 min-1. In addition, the results obtained provide clues as to the microenvironments of these functional groups, and indicate that the proteins studied undergo pH-dependent conformational changes which affect the microenvironment, and hence the chemical reactivity of these groups.", "contents": "A competitive labeling method for the determination of the chemical properties of solitary functional groups in proteins. The properties of the functional groups in a protein can be used as built-in-probes of the structure of the protein. We have developed a general procedure whereby the ionization constant and chemical reactivity of solitary functional groups in proteins may be determined. The method may be applied to the side chain of histidine, tyrosine, lysine, and cysteine, as well as to the amino terminus of the protein. The method, which is an extension of the competitive labeling technique using [3H]- and [14C]1-fluoro-2,4-dinitrobenzene (N2ph-F) in a double-labeling procedure, is rapid and sensitive. Advantage is taken of the fact that after acid hydrolysis of a dinitrophenylated protein, a derivative is obtained which must be derived from a unique position in the protein. The method has been applied to the solitary histidine residue of lysozyme, alpha-lytic protease, and Streptomyces griseus (S.G.) trypsin, as well as to the amino terminus of the latter protein. The following parameters were obtained for reaction with N2ph-F at 20 degrees C in 0.1 N KCl: the histidine of hen egg-white lysozyme, pKa of 6.4 and second-order velocity constant of 0.188 M-1 min-1; the histidine of alpha-lytic protease, pKa of 6.5 and second-order velocity constant of 0.0235 M-1 min-1; the histidine of S.G. trypsin, pKa of 6.5 and second-order velocity constant of 0.0328 M-1 min-1; the valyl amino terminus of S.G. trypsin, pKa of 8.1 and second-order velocity constant of 0.403 M-1 min-1. In addition, the results obtained provide clues as to the microenvironments of these functional groups, and indicate that the proteins studied undergo pH-dependent conformational changes which affect the microenvironment, and hence the chemical reactivity of these groups."}
{"id": "PMID:43", "title": "Modification of arginine and lysine in proteins with 2,4-pentanedione.", "content": "Primary amines react with 2,4-pentanedione at pH 6-9 to form enamines, N-alkyl-4-amino-3-penten-2-ones. The latter compounds readily regenerate the primary amine at low pH or on treatment with hydroxylamine. Guanidine and substituted guanidines react with 2,4-pentanedione to form N-substituted 2-amino-4,6-dimethylpyrimidines at a rate which is lower by at least a factor of 20 than the rate of reaction of 2,4-pentanedione with primary amines. Selective modification of lysine and arginine side chains in proteins can readily be achieved with 2,4-pentanedione. Modification of lysine is favored by reaction at pH 7 or for short reaction times at pH 9. Selective modification of arginine is achieved by reaction with 2,4-pentanedione for long times at pH 9, followed by treatment of the protein with hydroxylamine. The extent of modification of lysine and arginine side chains can readily be measured spectrophotometrically. Modification of lysozyme with 2,4-pentanedione at pH 7 results in modification of 3.8 lysine residues and less than 0.4 arginine residue in 24 hr. Modification of lysozyme with 2,4-pentanedione at pH 9 results in modification of 4 lysine residues and 4.5 arginine residues in 100 hr. Treatment of this modified protein with hydroxylamine regenerated the modified lysine residues but caused no change in the modified arginine residues. One arginine residue seems to be essential for the catalytic activity of the enzyme.", "contents": "Modification of arginine and lysine in proteins with 2,4-pentanedione. Primary amines react with 2,4-pentanedione at pH 6-9 to form enamines, N-alkyl-4-amino-3-penten-2-ones. The latter compounds readily regenerate the primary amine at low pH or on treatment with hydroxylamine. Guanidine and substituted guanidines react with 2,4-pentanedione to form N-substituted 2-amino-4,6-dimethylpyrimidines at a rate which is lower by at least a factor of 20 than the rate of reaction of 2,4-pentanedione with primary amines. Selective modification of lysine and arginine side chains in proteins can readily be achieved with 2,4-pentanedione. Modification of lysine is favored by reaction at pH 7 or for short reaction times at pH 9. Selective modification of arginine is achieved by reaction with 2,4-pentanedione for long times at pH 9, followed by treatment of the protein with hydroxylamine. The extent of modification of lysine and arginine side chains can readily be measured spectrophotometrically. Modification of lysozyme with 2,4-pentanedione at pH 7 results in modification of 3.8 lysine residues and less than 0.4 arginine residue in 24 hr. Modification of lysozyme with 2,4-pentanedione at pH 9 results in modification of 4 lysine residues and 4.5 arginine residues in 100 hr. Treatment of this modified protein with hydroxylamine regenerated the modified lysine residues but caused no change in the modified arginine residues. One arginine residue seems to be essential for the catalytic activity of the enzyme."}
{"id": "PMID:44", "title": "The origin of the alkaline inactivation of pepsinogen.", "content": "Above pH 8.5, pepsinogen is converted into a form which cannot be activated to pepsin on exposure to low pH. Intermediate exposure to neutral pH, however, returns the protein to a form which can be activated. Evidence is presented for a reversible, small conformational change in the molecule, distinct from the unfolding of the protein. At the same time, the molecule is converted to a form of limited solubility, which is precipitated at low pH, where activation is normally seen. The results are interpreted in terms of the peculiar structure of the pepsinogen molecule. Titration of the basic NH2-terminal region produced an open form, which can return to the native form at neutral pH, but which is maintained at low pH by neutralization of carboxylate groups in the pepsin portion.", "contents": "The origin of the alkaline inactivation of pepsinogen. Above pH 8.5, pepsinogen is converted into a form which cannot be activated to pepsin on exposure to low pH. Intermediate exposure to neutral pH, however, returns the protein to a form which can be activated. Evidence is presented for a reversible, small conformational change in the molecule, distinct from the unfolding of the protein. At the same time, the molecule is converted to a form of limited solubility, which is precipitated at low pH, where activation is normally seen. The results are interpreted in terms of the peculiar structure of the pepsinogen molecule. Titration of the basic NH2-terminal region produced an open form, which can return to the native form at neutral pH, but which is maintained at low pH by neutralization of carboxylate groups in the pepsin portion."}
{"id": "PMID:45", "title": "Bovine liver dihydrofolate reductase: purification and properties of the enzyme.", "content": "A purification procedure is reported for obtaining bovine liver dihydrofolate reductase in high yield and amounts of 100-200 mg. A key step in the procedure is the use of an affinity gel prepared by coupling pteroyl-L-lysine to Sepharose. The purified reductase has a specific activity of about 100 units/mg and is homogeneous as judged by analytical ultracentrifugation, polyacrylamide gel electrophoresis, and titration with methotrexate. The products of the first step of Edman degradation indicated a minimum purity of 79%. The reductase has a molecular weight of about 21500 on the basis of amino acid composition and 22100 +/- 300 from equilibrium sedimentation. It is not inhibited by antiserum to the Streptococcus faecium reductase (isoenzyme 2). Unlike the reductase of many other vertebrate tissues, the bovine enzyme is inhibited by mercurials rather than activated and it has a single pH optimum at both low and high ionic strength. However, the position of the pH optimum is shifted and the activity increased by increasing ionic strength. Automatic Edman degradation has been used to determine 34 of the amino-terminal 37 amino acid residues. Considerable homology exists between this region and the corresponding regions of the reductase from S. faecium and from Escherichia coli. This strengthens the idea that this region contributes to the structure of the binding site for dihydrofolate.", "contents": "Bovine liver dihydrofolate reductase: purification and properties of the enzyme. A purification procedure is reported for obtaining bovine liver dihydrofolate reductase in high yield and amounts of 100-200 mg. A key step in the procedure is the use of an affinity gel prepared by coupling pteroyl-L-lysine to Sepharose. The purified reductase has a specific activity of about 100 units/mg and is homogeneous as judged by analytical ultracentrifugation, polyacrylamide gel electrophoresis, and titration with methotrexate. The products of the first step of Edman degradation indicated a minimum purity of 79%. The reductase has a molecular weight of about 21500 on the basis of amino acid composition and 22100 +/- 300 from equilibrium sedimentation. It is not inhibited by antiserum to the Streptococcus faecium reductase (isoenzyme 2). Unlike the reductase of many other vertebrate tissues, the bovine enzyme is inhibited by mercurials rather than activated and it has a single pH optimum at both low and high ionic strength. However, the position of the pH optimum is shifted and the activity increased by increasing ionic strength. Automatic Edman degradation has been used to determine 34 of the amino-terminal 37 amino acid residues. Considerable homology exists between this region and the corresponding regions of the reductase from S. faecium and from Escherichia coli. This strengthens the idea that this region contributes to the structure of the binding site for dihydrofolate."}
{"id": "PMID:46", "title": "Purification and properties of Escherichia coli dihydrofolate reductase.", "content": "Dihydrofolate reductase has been purified 40-fold to apparent homogeneity from a trimethoprim-resistant strain of Escherichia coli (RT 500) using a procedure that includes methotrexate affinity column chromatography. Determinations of the molecular weight of the enzyme based on its amino acid composition, sedimentation velocity, and sodium dodecyl sulfate gel electrophoresis gave values of 17680, 17470 and 18300, respectively. An aggregated form of the enzyme with a low specific activity can be separated from the monomer by gel filtration; treatment of the aggregate with mercaptoethanol or dithiothreitol results in an increase in enzymic activity and a regeneration of the monomer. Also, multiple molecular forms of the monomer have been detected by polyacrylamide gel electrophoresis. The unresolved enzyme exhibits two pH optima (pH 4.5 and pH 7.0) with dihydrofolate as a substrate. Highest activities are observed in buffers containing large organic cations. In 100 mM imidazolium chloride (pH 7), the specific activity is 47 mumol of dihydrofolate reduced per min per mg at 30 degrees. Folic acid also serves as a substrate with a single pH optimum of pH 4.5. At this pH the Km for folate is 16 muM, and the Vmax is 1/1000 of the rate observed with dihydrofolate as the substrate. Monovalent cations (Na+, K+, Rb+, and Cs+) inhibit dihydrofolate reductase; at a given ionic strength the degree of inhibition is a function of the ionic radius of the cation. Divalent cations are more potent inhibitors; the I50 of BaCl2 is 250 muM, as compared to 125 mM for KCl. Anions neither inhibit nor activate the enzyme.", "contents": "Purification and properties of Escherichia coli dihydrofolate reductase. Dihydrofolate reductase has been purified 40-fold to apparent homogeneity from a trimethoprim-resistant strain of Escherichia coli (RT 500) using a procedure that includes methotrexate affinity column chromatography. Determinations of the molecular weight of the enzyme based on its amino acid composition, sedimentation velocity, and sodium dodecyl sulfate gel electrophoresis gave values of 17680, 17470 and 18300, respectively. An aggregated form of the enzyme with a low specific activity can be separated from the monomer by gel filtration; treatment of the aggregate with mercaptoethanol or dithiothreitol results in an increase in enzymic activity and a regeneration of the monomer. Also, multiple molecular forms of the monomer have been detected by polyacrylamide gel electrophoresis. The unresolved enzyme exhibits two pH optima (pH 4.5 and pH 7.0) with dihydrofolate as a substrate. Highest activities are observed in buffers containing large organic cations. In 100 mM imidazolium chloride (pH 7), the specific activity is 47 mumol of dihydrofolate reduced per min per mg at 30 degrees. Folic acid also serves as a substrate with a single pH optimum of pH 4.5. At this pH the Km for folate is 16 muM, and the Vmax is 1/1000 of the rate observed with dihydrofolate as the substrate. Monovalent cations (Na+, K+, Rb+, and Cs+) inhibit dihydrofolate reductase; at a given ionic strength the degree of inhibition is a function of the ionic radius of the cation. Divalent cations are more potent inhibitors; the I50 of BaCl2 is 250 muM, as compared to 125 mM for KCl. Anions neither inhibit nor activate the enzyme."}
{"id": "PMID:47", "title": "The influence of pH on the interaction of inhibitors with triosephosphate isomerase and determination of the pKa of the active-site carboxyl group.", "content": "Ionization effects on the binding of the potential transition state analogues 2-phosphoglycolate and 2-phosphoglycolohydroxamate appear to be attributable to the changing state of ionization of the ligands themselves, therefore it is unnecessary to postulate the additional involvement of an ionizing residue at the active site of triosephosphate isomerase to explain the influence of changing pH on Ki in the neutral range. The binding of the competitive inhibitor inorganic sulfate is insensitive to changing pH in the neutral range. 3-Chloroacetol sulfate, synthesized as an active-site-specific reagent for triosephosphate isomerase, is used to provide an indication of the pKa of the essential carboxyl group of this enzyme. Previously described active-site-specific reagents for the isomerase were phosphate esters, and their changing state of ionization (accompanied by possible changes in their affinity for the active site) may have complicated earlier attempts to determine the pKa of the essential carboxyl group from the pH dependence of the rate of inactivation. Being a strong monoprotic acid, chloroacetol sulfate is better suited to the determination of the pKa of the carboxyl group. Chloroacetol sulfate inactivates triosephosphate isomerase by the selective esterification of the same carboxyl group as that which is esterified by the phosphate esters described earlier. From the pH dependence of the rate of inactivation of yeast triosephosphate isomerase, the apparent pKa of the active-site carboxyl group is estimated as 3.9 +/- 0.1.", "contents": "The influence of pH on the interaction of inhibitors with triosephosphate isomerase and determination of the pKa of the active-site carboxyl group. Ionization effects on the binding of the potential transition state analogues 2-phosphoglycolate and 2-phosphoglycolohydroxamate appear to be attributable to the changing state of ionization of the ligands themselves, therefore it is unnecessary to postulate the additional involvement of an ionizing residue at the active site of triosephosphate isomerase to explain the influence of changing pH on Ki in the neutral range. The binding of the competitive inhibitor inorganic sulfate is insensitive to changing pH in the neutral range. 3-Chloroacetol sulfate, synthesized as an active-site-specific reagent for triosephosphate isomerase, is used to provide an indication of the pKa of the essential carboxyl group of this enzyme. Previously described active-site-specific reagents for the isomerase were phosphate esters, and their changing state of ionization (accompanied by possible changes in their affinity for the active site) may have complicated earlier attempts to determine the pKa of the essential carboxyl group from the pH dependence of the rate of inactivation. Being a strong monoprotic acid, chloroacetol sulfate is better suited to the determination of the pKa of the carboxyl group. Chloroacetol sulfate inactivates triosephosphate isomerase by the selective esterification of the same carboxyl group as that which is esterified by the phosphate esters described earlier. From the pH dependence of the rate of inactivation of yeast triosephosphate isomerase, the apparent pKa of the active-site carboxyl group is estimated as 3.9 +/- 0.1."}
{"id": "PMID:48", "title": "Monoanion inhibition and 35Cl nuclear magnetic resonance studies of renal dipeptidase.", "content": "Kinetic analyses of monoanion inhibition and 15Cl nuclear magnetic resonance at 5.88 MHz were employed to study monoanion interactions with the zinc metalloenzyme, renal dipeptidase. The enzyme-catalyzed hydrolysis of glycyldehydrophenylalanine exhibited competitive inhibition when the reaction rate was determined in the presence of the monovalent anions fluoride, chloride, bromide, iodide, azide, nitrate, or thiocyanate or upon the addition of the divalent anion, sulfate. Competitive inhibition was produced by these anions. One anion was bound per enzyme molecule, and except in the case of fluoride all of the anions appeared to bind at the same site. Cyanide ion produced a much more effective inhibition of renal dipeptidase than the other monoanions, and it was shown that two cyanide ions were bound per enzyme molecule. An investigation of the effect of pH upon monoanion inhibition suggested that the anion inhibitors bind to the group with a pK of approximately 7.8. Complete dissociation of this group (approximately pH 8.4) eliminates the inhibitory effect of anions. The 35Cl line broadening produced by renal dipeptidase in 0.5 M NaCl solutions was 100 times more effective than that produced by equivalent concentrations of aquozinc(II). The line broadening was dependent upon the concentration of the metalloenzyme and independent of the frequency of the exciting radiation. When zinc ion was removed from the metalloenzyme by dialysis or when chloride was titrated from the metalloenzyme by cyanide, line broadening was decreased. Treatment of renal dipeptidase with saturating concentrations of the competitive inhibitor, guanosine triphosphate, in the presence of 0.5 M NaCl also produced a significant decrease in the 35Cl line width. The 35Cl line broadening produced by renal dipeptidase was shown to decrease with increasing pH through the range pH 5.8-10.8. This line-width variation with pH appeared to result from the titration of a site on the metalloprotein with an approximate pK of 7.4. Temperature studies of 35Cl line broadening by the metalloenzyme in the presence of chloride and cyanide inhibitors suggest that the fast exchange process pertains and that the dominant relaxation mechanism is quadrupolar in nature.", "contents": "Monoanion inhibition and 35Cl nuclear magnetic resonance studies of renal dipeptidase. Kinetic analyses of monoanion inhibition and 15Cl nuclear magnetic resonance at 5.88 MHz were employed to study monoanion interactions with the zinc metalloenzyme, renal dipeptidase. The enzyme-catalyzed hydrolysis of glycyldehydrophenylalanine exhibited competitive inhibition when the reaction rate was determined in the presence of the monovalent anions fluoride, chloride, bromide, iodide, azide, nitrate, or thiocyanate or upon the addition of the divalent anion, sulfate. Competitive inhibition was produced by these anions. One anion was bound per enzyme molecule, and except in the case of fluoride all of the anions appeared to bind at the same site. Cyanide ion produced a much more effective inhibition of renal dipeptidase than the other monoanions, and it was shown that two cyanide ions were bound per enzyme molecule. An investigation of the effect of pH upon monoanion inhibition suggested that the anion inhibitors bind to the group with a pK of approximately 7.8. Complete dissociation of this group (approximately pH 8.4) eliminates the inhibitory effect of anions. The 35Cl line broadening produced by renal dipeptidase in 0.5 M NaCl solutions was 100 times more effective than that produced by equivalent concentrations of aquozinc(II). The line broadening was dependent upon the concentration of the metalloenzyme and independent of the frequency of the exciting radiation. When zinc ion was removed from the metalloenzyme by dialysis or when chloride was titrated from the metalloenzyme by cyanide, line broadening was decreased. Treatment of renal dipeptidase with saturating concentrations of the competitive inhibitor, guanosine triphosphate, in the presence of 0.5 M NaCl also produced a significant decrease in the 35Cl line width. The 35Cl line broadening produced by renal dipeptidase was shown to decrease with increasing pH through the range pH 5.8-10.8. This line-width variation with pH appeared to result from the titration of a site on the metalloprotein with an approximate pK of 7.4. Temperature studies of 35Cl line broadening by the metalloenzyme in the presence of chloride and cyanide inhibitors suggest that the fast exchange process pertains and that the dominant relaxation mechanism is quadrupolar in nature."}
{"id": "PMID:49", "title": "The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: inactivation of the enzyme.", "content": "Bovine erythrocyte superoxide dismutase was slowly and irreversibly inactivated by hydrogen peroxide. The rate of this inactivation was directly dependent upon the concentrations of both H2O2 and of enzyme, and its second-order rate constant at pH 10.0 and 25 degrees was 6.7 M-1 sec-1. Inactivation was preceded by a bleaching due to rapid reduction of Cu2+ on the enzyme, and following this there was a gradual reappearance of a new absorption in the visible region, which was coincident with the loss of catalytic activity. Inactivation of the enzyme was pH-dependent and indicated an essential ionization whose pKa was approximately 10.2. Replacement of H2O by D2O raised this pKa but did not diminish the catalytic activity of superoxide dismutase, measured at pH 10.0. Several compounds, including xanthine, urate, formate, and azide, protected the enzyme against inactivation by H2O2. Alcohols and benzoate, which scavenge hydroxyl radical, did not protect. Compounds with special affinity for singlet oxygen were similarly ineffective. The data were interpreted in terms of the reduction of the enzyme-bound Cu2+ to Cu+, by H2O2, followed by a Fenton's type reaction of the Cu+ with additional H2O2. This would generate Cu2+-OH- or its ionized equivalent, Cu2+-O--, which could then oxidatively attack an adjacent histidine and thus inactivate the enzyme. Compounds which protected the enzyme could have done so by reacting with the bound oxidant, in competition with the adjacent histidine.", "contents": "The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: inactivation of the enzyme. Bovine erythrocyte superoxide dismutase was slowly and irreversibly inactivated by hydrogen peroxide. The rate of this inactivation was directly dependent upon the concentrations of both H2O2 and of enzyme, and its second-order rate constant at pH 10.0 and 25 degrees was 6.7 M-1 sec-1. Inactivation was preceded by a bleaching due to rapid reduction of Cu2+ on the enzyme, and following this there was a gradual reappearance of a new absorption in the visible region, which was coincident with the loss of catalytic activity. Inactivation of the enzyme was pH-dependent and indicated an essential ionization whose pKa was approximately 10.2. Replacement of H2O by D2O raised this pKa but did not diminish the catalytic activity of superoxide dismutase, measured at pH 10.0. Several compounds, including xanthine, urate, formate, and azide, protected the enzyme against inactivation by H2O2. Alcohols and benzoate, which scavenge hydroxyl radical, did not protect. Compounds with special affinity for singlet oxygen were similarly ineffective. The data were interpreted in terms of the reduction of the enzyme-bound Cu2+ to Cu+, by H2O2, followed by a Fenton's type reaction of the Cu+ with additional H2O2. This would generate Cu2+-OH- or its ionized equivalent, Cu2+-O--, which could then oxidatively attack an adjacent histidine and thus inactivate the enzyme. Compounds which protected the enzyme could have done so by reacting with the bound oxidant, in competition with the adjacent histidine."}
{"id": "PMID:50", "title": "Circular dichroism and fluorescence studies of homogeneous antibodies to type III pneumococcal polysaccharide.", "content": "The near-ultraviolet circular dichroism (CD) of three homogeneous anti-type III pneumococcal antibodies in the absence and the presence of the specific hexasaccharide ligand was studied. In addition recombinations and hybridizations of H and L chains derived from two of these antibodies were carried out and the CD spectra of bound and free reconstituted IgG molecules were measured. The results indicate that the CD spectra of the native antibodies in the 260-310-nm range are very similar in shape and sign and exhibit a positive band at 285 nm. The homologous reconstituted antibody molecules exhibited CD spectra very similar in shape and sign to those of the native antibody molecules although recombinant molecules are no longer stabilized by interchain disulfide bonds. Upon addition of the hexasaccharide ligand, a significant decrease in amplitude of the CD spectra (18-21%) occurred in all three native antibodies and their Fab fragments as well as in the homologous recombinant molecules. No CD spectral changes could be detected upon interaction of the hapten ligand with the heterologous recombinants. All homogeneous antibodies studied exhibited fluorescence quenching upon oligosaccharide binding and a blue shift of the emission maximum. This property allowed the determination of the binding constant of one selected antibody to be made. Taken together, CD and fluorescence spectroscopic data suggest that oligosaccharide ligands induced detectable conformational changes in the Fab fragment of the antibody.", "contents": "Circular dichroism and fluorescence studies of homogeneous antibodies to type III pneumococcal polysaccharide. The near-ultraviolet circular dichroism (CD) of three homogeneous anti-type III pneumococcal antibodies in the absence and the presence of the specific hexasaccharide ligand was studied. In addition recombinations and hybridizations of H and L chains derived from two of these antibodies were carried out and the CD spectra of bound and free reconstituted IgG molecules were measured. The results indicate that the CD spectra of the native antibodies in the 260-310-nm range are very similar in shape and sign and exhibit a positive band at 285 nm. The homologous reconstituted antibody molecules exhibited CD spectra very similar in shape and sign to those of the native antibody molecules although recombinant molecules are no longer stabilized by interchain disulfide bonds. Upon addition of the hexasaccharide ligand, a significant decrease in amplitude of the CD spectra (18-21%) occurred in all three native antibodies and their Fab fragments as well as in the homologous recombinant molecules. No CD spectral changes could be detected upon interaction of the hapten ligand with the heterologous recombinants. All homogeneous antibodies studied exhibited fluorescence quenching upon oligosaccharide binding and a blue shift of the emission maximum. This property allowed the determination of the binding constant of one selected antibody to be made. Taken together, CD and fluorescence spectroscopic data suggest that oligosaccharide ligands induced detectable conformational changes in the Fab fragment of the antibody."}
{"id": "PMID:51", "title": "Conformational changes induced in a homogeneous anti-type III pneumococcal antibody by oligosaccharides of increasing size.", "content": "The circular polarization of luminescence (CPL) emitted by tryptophan residues was used as a sensitive probe for measuring ligand-induced structural changes in a homogeneous type III pneumococcal antibody. A series of oligosaccharide ligands of increasing size derived from type III polysaccharide by partial acid hydrolysis was assayed. Ligand-induced changes in the circular polarization of fluorescence of the antibody were observed for all antigens tested, including tetra-, hexa-, and octasaccharides and a 16-residue oligomer, the largest changes being recorded upon interaction with the intact soluble type III pneumococcal (SIII) polysaccharide. When Fab' or F(ab')2 fragments were used instead of the antibody IgG for binding of SIII polysaccharide, the extent of conformational changes was decreased. This suggests interactions between Fab and Fc portions in the IgG molecule and subsequent conformational changes in Fc part upon antigen binding. Reduction of interchain disulfide bonds abolished the additional spectral changes attributed to the Fc part but not the changes observed in the Fab part, thus suggesting that the presence of the interchain disulfide bond in the hinge region is required for maximal CPL changes to occur. Small monovalent ligands, i.e., the tetra-, hexa-, and octasaccharides, were capable of inducing CPL changes in the Fab part of the antibody molecule as well as CPL changes attributed to the Fc portion. A multivalent ligand containing about 16 sugar residues appears to be the minimal antigenic size required for triggering conformational changes attributed to the Fc part, similar to those seen in the interaction with the whole polysaccharide antigen.", "contents": "Conformational changes induced in a homogeneous anti-type III pneumococcal antibody by oligosaccharides of increasing size. The circular polarization of luminescence (CPL) emitted by tryptophan residues was used as a sensitive probe for measuring ligand-induced structural changes in a homogeneous type III pneumococcal antibody. A series of oligosaccharide ligands of increasing size derived from type III polysaccharide by partial acid hydrolysis was assayed. Ligand-induced changes in the circular polarization of fluorescence of the antibody were observed for all antigens tested, including tetra-, hexa-, and octasaccharides and a 16-residue oligomer, the largest changes being recorded upon interaction with the intact soluble type III pneumococcal (SIII) polysaccharide. When Fab' or F(ab')2 fragments were used instead of the antibody IgG for binding of SIII polysaccharide, the extent of conformational changes was decreased. This suggests interactions between Fab and Fc portions in the IgG molecule and subsequent conformational changes in Fc part upon antigen binding. Reduction of interchain disulfide bonds abolished the additional spectral changes attributed to the Fc part but not the changes observed in the Fab part, thus suggesting that the presence of the interchain disulfide bond in the hinge region is required for maximal CPL changes to occur. Small monovalent ligands, i.e., the tetra-, hexa-, and octasaccharides, were capable of inducing CPL changes in the Fab part of the antibody molecule as well as CPL changes attributed to the Fc portion. A multivalent ligand containing about 16 sugar residues appears to be the minimal antigenic size required for triggering conformational changes attributed to the Fc part, similar to those seen in the interaction with the whole polysaccharide antigen."}
{"id": "PMID:52", "title": "Evidence of the involvement of a 50S ribosomal protein in several active sites.", "content": "The functional role of the Bacillus stearothermophilus 50S ribosomal protein B-L3 (probably homologous to the Escherichia coli protein L2) was examined by chemical modification. The complex [B-L3-23S RNA] was photooxidized in the presence of rose bengal and the modified protein incorporated by reconstitution into 50S ribosomal subunits containing all other unmodified components. Particles containing photooxidized B-L3 are defective in several functional assays, including (1) poly(U)-directed poly(Phe) synthesis, (2) peptidyltransferase activity, (3) ability to associate with a [30S-poly(U)-Phe-tRNA] complex, and (4) binding of elongation factor G and GTP. The rates of loss of the partial functional activities during photooxidation of B-L3 indicate that at least two independent inactivating events are occurring, a faster one, involving oxidation of one or more histidine residues, affecting peptidyltransferase and subunit association activities and a slower one affecting EF-G binding. Therefore the protein B-L3 has one or more histidine residues which are essential for peptidyltransferase and subunit association, and another residue which is essential for EF-G-GTP binding. B-L3 may be the ribosomal peptidyltransferase protein, or a part of the active site, and may contribute functional groups to the other active sites as well.", "contents": "Evidence of the involvement of a 50S ribosomal protein in several active sites. The functional role of the Bacillus stearothermophilus 50S ribosomal protein B-L3 (probably homologous to the Escherichia coli protein L2) was examined by chemical modification. The complex [B-L3-23S RNA] was photooxidized in the presence of rose bengal and the modified protein incorporated by reconstitution into 50S ribosomal subunits containing all other unmodified components. Particles containing photooxidized B-L3 are defective in several functional assays, including (1) poly(U)-directed poly(Phe) synthesis, (2) peptidyltransferase activity, (3) ability to associate with a [30S-poly(U)-Phe-tRNA] complex, and (4) binding of elongation factor G and GTP. The rates of loss of the partial functional activities during photooxidation of B-L3 indicate that at least two independent inactivating events are occurring, a faster one, involving oxidation of one or more histidine residues, affecting peptidyltransferase and subunit association activities and a slower one affecting EF-G binding. Therefore the protein B-L3 has one or more histidine residues which are essential for peptidyltransferase and subunit association, and another residue which is essential for EF-G-GTP binding. B-L3 may be the ribosomal peptidyltransferase protein, or a part of the active site, and may contribute functional groups to the other active sites as well."}
{"id": "PMID:53", "title": "The interaction of phospholipase A2 with micellar interfaces. The role of the N-terminal region.", "content": "The localization of the previously postulated interface recognition site (IRS) in porcine pancreatic phospholipase A2, required for a specific interaction between the enzyme and organized lipid-water interfaces, was investigated by ultraviolet difference spectroscopy, by measurements of the intrinsic fluorescence of the unique Trp residue, and by protection experiments against specific tryptic hydrolysis. Using the enzymically nondegradable substrate analogues: CnH(2n+1)(0-)OOCH2CH2N+(CH3)3-(H,OH), it is shown that the rather hydrophobic N-terminal sequence of the enzyme, viz., Ala-Leu-Trp-Gln-Phe-Arg, is directly involved in the interaction with the lipid-water interface. Besides hydrophobic probably also polar interactions contribute to the binding process. At neutral or acidic pH the presence of a salt bridge between the N-terminal alpha-NH3+ group and a negatively charged side chain stablizes the interface recognition site and allows the enzyme to penetrate micellar surfaces, even in the absence of metal ion. At alkaline pH, interaction of the enzyme with micellar interfaces requires the presence of Ca2+ (Ba2+) ions.", "contents": "The interaction of phospholipase A2 with micellar interfaces. The role of the N-terminal region. The localization of the previously postulated interface recognition site (IRS) in porcine pancreatic phospholipase A2, required for a specific interaction between the enzyme and organized lipid-water interfaces, was investigated by ultraviolet difference spectroscopy, by measurements of the intrinsic fluorescence of the unique Trp residue, and by protection experiments against specific tryptic hydrolysis. Using the enzymically nondegradable substrate analogues: CnH(2n+1)(0-)OOCH2CH2N+(CH3)3-(H,OH), it is shown that the rather hydrophobic N-terminal sequence of the enzyme, viz., Ala-Leu-Trp-Gln-Phe-Arg, is directly involved in the interaction with the lipid-water interface. Besides hydrophobic probably also polar interactions contribute to the binding process. At neutral or acidic pH the presence of a salt bridge between the N-terminal alpha-NH3+ group and a negatively charged side chain stablizes the interface recognition site and allows the enzyme to penetrate micellar surfaces, even in the absence of metal ion. At alkaline pH, interaction of the enzyme with micellar interfaces requires the presence of Ca2+ (Ba2+) ions."}
{"id": "PMID:54", "title": "Phospholipase A2 as a probe of phospholipid distribution in erythrocyte membranes. Factors influencing the apparent specificity of the reaction.", "content": "The action of snake venom phospholipases A2 in intact human erythrocytes was investigated in detail. The basis phospholipase from Agkistrodon halys blomhifii was found to induce both hydrolysis of membrane phospholipids and total cell hemolysis under certain experimental conditions. The hydrolytic action of the basic enzyme was found to consist of two sequential events: (a) hydrolysis of 70% of the total cell ph osphatidylcholine without any evident hemolysis; and (b) complete hydrolysis of the remaining phosphatidylcholine, followed closely by extensive phosphatidylethanolamine hydrolysis and finally with onset of hemolysis, attack on the phosphatidylserine. At pH 7.4 and 10 mM Ca2+ only stage (a) occurred. However, a slight elevation of the pH of incubation to pH 8.0 and/or inclusion of 40 mM Ca2+ in the reaction mixture caused both events (a) and (b) to occur. The addition of glucose limited the action of the enzyme to stage (a) under any reaction conditions. An investigation showed that enzymically induced hemolysis occurred under conditions where the intracellular ATP levels were lowered. Data are presented which suggest that stage (b) is mediated by in influx of Ca2+ into the cell when the levels of ATP are low. Interestingly the phosphllipase from Naja naja venom (Pakistan) yielded results similar to those observed with the basic enzyme from Agkistrodon venom. However, the enzyme from Crotalus adamanteus and the acidic enzyme also present in the Agkistrodon venom produced only slight hydrolysis or hemolysis under any of the conditions studied. Other species of erythrocytes, e.g., guinea pig, monkey, pig, and rat, were tested but only those from guinea pig behaved similarly to the human cells. Pig, monkey, and rat erythrocytes underwent very limited hydrolysis and hemolysis. It is evident that the use of these phospholipases to probe the localization of phospholipds in erythrocyte membranes must be approached with caution. Certain facets of this problem are discussed.", "contents": "Phospholipase A2 as a probe of phospholipid distribution in erythrocyte membranes. Factors influencing the apparent specificity of the reaction. The action of snake venom phospholipases A2 in intact human erythrocytes was investigated in detail. The basis phospholipase from Agkistrodon halys blomhifii was found to induce both hydrolysis of membrane phospholipids and total cell hemolysis under certain experimental conditions. The hydrolytic action of the basic enzyme was found to consist of two sequential events: (a) hydrolysis of 70% of the total cell ph osphatidylcholine without any evident hemolysis; and (b) complete hydrolysis of the remaining phosphatidylcholine, followed closely by extensive phosphatidylethanolamine hydrolysis and finally with onset of hemolysis, attack on the phosphatidylserine. At pH 7.4 and 10 mM Ca2+ only stage (a) occurred. However, a slight elevation of the pH of incubation to pH 8.0 and/or inclusion of 40 mM Ca2+ in the reaction mixture caused both events (a) and (b) to occur. The addition of glucose limited the action of the enzyme to stage (a) under any reaction conditions. An investigation showed that enzymically induced hemolysis occurred under conditions where the intracellular ATP levels were lowered. Data are presented which suggest that stage (b) is mediated by in influx of Ca2+ into the cell when the levels of ATP are low. Interestingly the phosphllipase from Naja naja venom (Pakistan) yielded results similar to those observed with the basic enzyme from Agkistrodon venom. However, the enzyme from Crotalus adamanteus and the acidic enzyme also present in the Agkistrodon venom produced only slight hydrolysis or hemolysis under any of the conditions studied. Other species of erythrocytes, e.g., guinea pig, monkey, pig, and rat, were tested but only those from guinea pig behaved similarly to the human cells. Pig, monkey, and rat erythrocytes underwent very limited hydrolysis and hemolysis. It is evident that the use of these phospholipases to probe the localization of phospholipds in erythrocyte membranes must be approached with caution. Certain facets of this problem are discussed."}
{"id": "PMID:55", "title": "Subunit interactions in yeast glyceraldehyde-3-phosphate dehydrogenase.", "content": "The spontaneous inactivation of yeast glyceraldehyde-3-phosphate dehydrogenase was found to fit a simple two-state model at pH 8.5 and 25 degrees. The first step is a relatively rapid dissociation of the tetramer to dimers with the equilibrium largely in favor of the tetramer. In the absence of NAD+ the dimer inactivates irreversibly. The apoenzyme is quite stable with a half-life for complete activity loss proportional to the square root of the enzyme concentration. Perturbances of the protein structure (by pH, ionic strength, and specific salts), which have no effect on the tetrameric state of the molecule, result in an alteration of the cooperativity of NAD+ binding, the reactivity of the active-site sulfhydryl group, and the catalytic activity of the enzyme. Covalent modification of two of the four active-site sulfhydryl groups has profound effects on the enzymic activity which are mediated by changes in the subunit interactions. Sedimentation analysis and hybridization studies indicate that the interaction between subunits remains strong after covalent modification. Under normal physiological and equilibrium dialysis conditions the protein is a tetramer. Equilibrium dialysis studies of NAD+ binding to the enzyme at pH 8.5 and 25 degrees reveal a mixed cooperativity pattern. A model consistent with these observations and the observed half-of-the-sites reactivity is that of ligand induced sequential conformational changes which are transferred across strongly interacting subunit domains. Methods for distinguishing negatively cooperative binding patterns from mixtures of denatured enzyme and multiple species are discussed.", "contents": "Subunit interactions in yeast glyceraldehyde-3-phosphate dehydrogenase. The spontaneous inactivation of yeast glyceraldehyde-3-phosphate dehydrogenase was found to fit a simple two-state model at pH 8.5 and 25 degrees. The first step is a relatively rapid dissociation of the tetramer to dimers with the equilibrium largely in favor of the tetramer. In the absence of NAD+ the dimer inactivates irreversibly. The apoenzyme is quite stable with a half-life for complete activity loss proportional to the square root of the enzyme concentration. Perturbances of the protein structure (by pH, ionic strength, and specific salts), which have no effect on the tetrameric state of the molecule, result in an alteration of the cooperativity of NAD+ binding, the reactivity of the active-site sulfhydryl group, and the catalytic activity of the enzyme. Covalent modification of two of the four active-site sulfhydryl groups has profound effects on the enzymic activity which are mediated by changes in the subunit interactions. Sedimentation analysis and hybridization studies indicate that the interaction between subunits remains strong after covalent modification. Under normal physiological and equilibrium dialysis conditions the protein is a tetramer. Equilibrium dialysis studies of NAD+ binding to the enzyme at pH 8.5 and 25 degrees reveal a mixed cooperativity pattern. A model consistent with these observations and the observed half-of-the-sites reactivity is that of ligand induced sequential conformational changes which are transferred across strongly interacting subunit domains. Methods for distinguishing negatively cooperative binding patterns from mixtures of denatured enzyme and multiple species are discussed."}
{"id": "PMID:56", "title": "Kinetic light scattering studies on the dissociation of hemoglobin from Lumbricus terrestris.", "content": "The kinetics of the pH-induced dissociation of the 3 X 10(6) mol wt hemoglobin from Lumbricus terrestris (the earthworm) have been studied in a light-scattering stopped-flow apparatus. The ligand dependent dissociation data were fit well by a simple sequential model. The data for CO and oxyhemoglobin are consistent with Hb12 leads to 2Hb6 leads to 12Hb. Methemoglobin at pH 7 appears to be hexameric and the dissociation is consistent with the model: Hb6 leads to 6Hb. In a sequential decay scheme for which light-scattering changes are monitored, the relative amounts of rapid and slow phase are determined by the rate constants as well as the molecular weights of intermediate species. Assignment of the hexameric intermediate is supported by an investigation of the sensitivity of the theoretical kinetic curves to the molecular weights of the intermediates. This assignment is further supported by the following: (1) the same model will fit the data for oxy- and CO-hemoglobin at all three temperatures (a 24-29-fold variation in rate constants), (2) evidence from electron microscopy shows hexameric forms, and (3) methemoglobin is apparently stable as a hexamer at pH 7. When CO replaces O2 as the ligand, the dissociation rate increases by a factor of four. The met is about 20 times faster than the initial oxyhemoglobin dissociation rate, but perhaps more relevant for comparing dissociation of the hexamer, the met rate was respectively 100 times and 500 times faster than that for the assumed hexameric forms of CO- and oxy-hemoglobin. The activation energies for the dodecamer to hexamer dissociation and for the dissociation of the hexamer to smaller forms were about 30 kcal/mol for oxy-, CO-, and methemoglobin.", "contents": "Kinetic light scattering studies on the dissociation of hemoglobin from Lumbricus terrestris. The kinetics of the pH-induced dissociation of the 3 X 10(6) mol wt hemoglobin from Lumbricus terrestris (the earthworm) have been studied in a light-scattering stopped-flow apparatus. The ligand dependent dissociation data were fit well by a simple sequential model. The data for CO and oxyhemoglobin are consistent with Hb12 leads to 2Hb6 leads to 12Hb. Methemoglobin at pH 7 appears to be hexameric and the dissociation is consistent with the model: Hb6 leads to 6Hb. In a sequential decay scheme for which light-scattering changes are monitored, the relative amounts of rapid and slow phase are determined by the rate constants as well as the molecular weights of intermediate species. Assignment of the hexameric intermediate is supported by an investigation of the sensitivity of the theoretical kinetic curves to the molecular weights of the intermediates. This assignment is further supported by the following: (1) the same model will fit the data for oxy- and CO-hemoglobin at all three temperatures (a 24-29-fold variation in rate constants), (2) evidence from electron microscopy shows hexameric forms, and (3) methemoglobin is apparently stable as a hexamer at pH 7. When CO replaces O2 as the ligand, the dissociation rate increases by a factor of four. The met is about 20 times faster than the initial oxyhemoglobin dissociation rate, but perhaps more relevant for comparing dissociation of the hexamer, the met rate was respectively 100 times and 500 times faster than that for the assumed hexameric forms of CO- and oxy-hemoglobin. The activation energies for the dodecamer to hexamer dissociation and for the dissociation of the hexamer to smaller forms were about 30 kcal/mol for oxy-, CO-, and methemoglobin."}
{"id": "PMID:57", "title": "The reversible reduction of horse metmyoglobin by the iron(II) complex of trans-1,2-diaminocyclohexane-N,N,N,n-tetraacetate.", "content": "The reduction of metmyoglobin by the iron(II) complex of trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetate (FeCDTA2-) has been investigated. The equilibrium constant, measured spectrophotometrically, is 0.21 with a resulting reduction potential of 0.050 V for Mb0. The rate constant for the reduction is 28 M-1 sec-1 with a deltaH ++ of 13 kcal M-1 and deltaS ++ of -11 eu. Both CN- and OH- inhibit the reduction because of the relatively low reactivity of cyanometmyoglobin (Mb+CN-) and ionized metmyglobin (Mb+OH-). The rate constant for the reduction of Mb+CN- by FeCDTA2- is 4.0 X 10(-2) M-1 sec-1 and that for reduction of Mb+OH- is 4.8 M-1 sec-1. The nitric oxide complex of metmyoglobin is reduced with a rate constant of 10 M-1 sec-1. The kinetics of oxidation of oxymyoglobin by FeCDTA- were studied. The data are consistent with a mechanism where oxidation takes place entirely through the deoxy form. A rate constant of 1.45 X 10(2) M-1 sec-1 was calculated for the oxidation of deoxymyoglobin by FeCDTA-, in equilibrium constant and rate constant for reduction. The above data are discussed in terms of a simple outer-sphere reduction reaction.", "contents": "The reversible reduction of horse metmyoglobin by the iron(II) complex of trans-1,2-diaminocyclohexane-N,N,N,n-tetraacetate. The reduction of metmyoglobin by the iron(II) complex of trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetate (FeCDTA2-) has been investigated. The equilibrium constant, measured spectrophotometrically, is 0.21 with a resulting reduction potential of 0.050 V for Mb0. The rate constant for the reduction is 28 M-1 sec-1 with a deltaH ++ of 13 kcal M-1 and deltaS ++ of -11 eu. Both CN- and OH- inhibit the reduction because of the relatively low reactivity of cyanometmyoglobin (Mb+CN-) and ionized metmyglobin (Mb+OH-). The rate constant for the reduction of Mb+CN- by FeCDTA2- is 4.0 X 10(-2) M-1 sec-1 and that for reduction of Mb+OH- is 4.8 M-1 sec-1. The nitric oxide complex of metmyoglobin is reduced with a rate constant of 10 M-1 sec-1. The kinetics of oxidation of oxymyoglobin by FeCDTA- were studied. The data are consistent with a mechanism where oxidation takes place entirely through the deoxy form. A rate constant of 1.45 X 10(2) M-1 sec-1 was calculated for the oxidation of deoxymyoglobin by FeCDTA-, in equilibrium constant and rate constant for reduction. The above data are discussed in terms of a simple outer-sphere reduction reaction."}
{"id": "PMID:58", "title": "Constitution and properties of axonal membranes of crustacean nerves.", "content": "The purification of axonal membranes of crustaceans was followed by measuring enrichment in [3H]tetrodotoxin binding capacity and in Na+, K+-ATPase activity. A characteristic of these membranes is their high content of lipids and their low content of protein as compared to other types of plasmatic membranes. The axonal membrane contains myosin-like, actin-like, tropomyosin-like, and tubulin-like proteins. It also contains Na+, K+-ATPase and acetylcholinesterase. The molecular weights of these two enzymes after solubilization are 280,000 and 270,000, respectively. The molecular weights of the catalytic subunits are 96,000 for ATPase and 71,000 for acetylcholinesterase. We confirmed the presence of a nicotine binding component in the axonal membrane of the lobster but we have been unable to find [3H]nicotine binding to crab axonal membranes. The binding to axonal membranes og of the sodium channel, has been studied in detail. The dissociation constant for the binding of [3H]tetrodotoxin to the axonal membrane receptor is 2.9 nM at pH 7.4. The concentration of the tetrodotoxin receptor in crustacean membranes is about 10 pmol/mg of membrane protein, 7 times less than the acetylcholinesterase, 30 times less than the Na+, K+-ATPase, and 30 times less than the nicotine binding component in the lobster membrane. A reasonable estimate indicates that approximately only one peptide chain in 1000 constitutes the tetrodotoxin binding part of the sodium channel in the axonal membrane. Veratridine, which acts selectively on the resting sodium permeability, binds to the phospholipid part of the axonal membrane. [3H]Veratridine binding to membranes parallels the electrophysiological effect. Veratridine and tetrodotoxin have different receptor sites. Although tetrodotoxin can repolarize the excitable membrane of a giant axon depolarized by veratridine, veratridine does not affect the binding of [3H]tetrodotoxin to purified axonal membranes. Similarly, tetrodotoxin does not affect the binding of [3H]veratridine to axonal membranes. Scorpion neurotoxin I, a presynaptic toxin which affects both the Na+ and the K+ channels, does not interfere with the binding of [3H]tetrodotoxin or [3H]veratridine to axonal membranes. Tetrodotoxin, veratridine, and scorpion neurotoxin I, which have in common the perturbation of the normal functioning of the sodium channel, act upon three different types of receptor sites.", "contents": "Constitution and properties of axonal membranes of crustacean nerves. The purification of axonal membranes of crustaceans was followed by measuring enrichment in [3H]tetrodotoxin binding capacity and in Na+, K+-ATPase activity. A characteristic of these membranes is their high content of lipids and their low content of protein as compared to other types of plasmatic membranes. The axonal membrane contains myosin-like, actin-like, tropomyosin-like, and tubulin-like proteins. It also contains Na+, K+-ATPase and acetylcholinesterase. The molecular weights of these two enzymes after solubilization are 280,000 and 270,000, respectively. The molecular weights of the catalytic subunits are 96,000 for ATPase and 71,000 for acetylcholinesterase. We confirmed the presence of a nicotine binding component in the axonal membrane of the lobster but we have been unable to find [3H]nicotine binding to crab axonal membranes. The binding to axonal membranes og of the sodium channel, has been studied in detail. The dissociation constant for the binding of [3H]tetrodotoxin to the axonal membrane receptor is 2.9 nM at pH 7.4. The concentration of the tetrodotoxin receptor in crustacean membranes is about 10 pmol/mg of membrane protein, 7 times less than the acetylcholinesterase, 30 times less than the Na+, K+-ATPase, and 30 times less than the nicotine binding component in the lobster membrane. A reasonable estimate indicates that approximately only one peptide chain in 1000 constitutes the tetrodotoxin binding part of the sodium channel in the axonal membrane. Veratridine, which acts selectively on the resting sodium permeability, binds to the phospholipid part of the axonal membrane. [3H]Veratridine binding to membranes parallels the electrophysiological effect. Veratridine and tetrodotoxin have different receptor sites. Although tetrodotoxin can repolarize the excitable membrane of a giant axon depolarized by veratridine, veratridine does not affect the binding of [3H]tetrodotoxin to purified axonal membranes. Similarly, tetrodotoxin does not affect the binding of [3H]veratridine to axonal membranes. Scorpion neurotoxin I, a presynaptic toxin which affects both the Na+ and the K+ channels, does not interfere with the binding of [3H]tetrodotoxin or [3H]veratridine to axonal membranes. Tetrodotoxin, veratridine, and scorpion neurotoxin I, which have in common the perturbation of the normal functioning of the sodium channel, act upon three different types of receptor sites."}
{"id": "PMID:59", "title": "Regulation of nitrogen fixation. Nitrogenase-derepressed mutants of Klebsiella pneumoniae.", "content": "1. A new procedure is described for selecting nitrogenase-derepressed mutants based on the method of Brenchley et al. (Brenchley, J.E., Prival, M.J. and Magasanik, B. (1973) J. Biol. Chem. 248, 6122-6128) for isolating histidase-constitutive mutants of a non-N2-fixing bacterium. 2. Nitrogenase levels of the new mutants in the presence of NH4+ were as high as 100% of the nitrogenase activity detected in the absence of NH4+. 3. Biochemical characterization of these nitrogen fixation (nif) derepressed mutants reveals that they fall into three classes. Three mutants (strains SK-24, 28 and 29), requiring glutamate for growth, synthesize nitrogenase and glutamine synthetase constitutively (in the presence of NH4+). A second class of mutants (strains SK-27 and 37) requiring glutamine for growth produces derepressed levels of nitrogenase activity and synthesized catalytically inactive glutamine synthetase protein, as determined immunologically. A third class of glutamine-requiring, nitrogenase-derepressed mutants (strain SK-25 and 26) synthesizes neither a catalytically active glutamine synthetase enzyme nor an immunologically cross-reactive glutamine synthetase protein. 4. F-prime complementation analysis reveals that the mutant strains SK-25, 26, 27, 37 map in a segment of the Klebsiella chromosome corresponding to the region coding for glutamine synthetase. Since the mutant strains SK-27 and SK-37 produce inactive glutamine synthetase protein, it is concluded that these mutations map within the glutamine synthetase structural gene.", "contents": "Regulation of nitrogen fixation. Nitrogenase-derepressed mutants of Klebsiella pneumoniae. 1. A new procedure is described for selecting nitrogenase-derepressed mutants based on the method of Brenchley et al. (Brenchley, J.E., Prival, M.J. and Magasanik, B. (1973) J. Biol. Chem. 248, 6122-6128) for isolating histidase-constitutive mutants of a non-N2-fixing bacterium. 2. Nitrogenase levels of the new mutants in the presence of NH4+ were as high as 100% of the nitrogenase activity detected in the absence of NH4+. 3. Biochemical characterization of these nitrogen fixation (nif) derepressed mutants reveals that they fall into three classes. Three mutants (strains SK-24, 28 and 29), requiring glutamate for growth, synthesize nitrogenase and glutamine synthetase constitutively (in the presence of NH4+). A second class of mutants (strains SK-27 and 37) requiring glutamine for growth produces derepressed levels of nitrogenase activity and synthesized catalytically inactive glutamine synthetase protein, as determined immunologically. A third class of glutamine-requiring, nitrogenase-derepressed mutants (strain SK-25 and 26) synthesizes neither a catalytically active glutamine synthetase enzyme nor an immunologically cross-reactive glutamine synthetase protein. 4. F-prime complementation analysis reveals that the mutant strains SK-25, 26, 27, 37 map in a segment of the Klebsiella chromosome corresponding to the region coding for glutamine synthetase. Since the mutant strains SK-27 and SK-37 produce inactive glutamine synthetase protein, it is concluded that these mutations map within the glutamine synthetase structural gene."}
{"id": "PMID:60", "title": "The reaction between the superoxide anion radical and cytochrome c.", "content": "1. The superoxide anion radical (O2-) reacts with ferricytochrome c to form ferrocytochrome c. No intermediate complexes are observable. No reaction could be detected between O2- and ferrocytochrome c. 2. At 20 degrees C the rate constant for the reaction at pH 4.7 to 6.7 is 1.4-10(6) M-1. S -1 and as the pH increases above 6.7 the rate constant steadily decreases. The dependence on pH is the same for tuna heart and horse heart cytochrome c. No reaction could be demonstrated between O2- and the form of cytochrome c which exists above pH approximately 9.2. The dependence of the rate constant on pH can be explained if cytochrome c has pKs of 7.45 and 9.2, and O2- reacts with the form present below pH 7.45 with k = 1.4-10(6) M-1 - S-1, the form above pH 7.45 with k = 3.0- 10(5) M-1 - S-1, and the form present above pH 9.2 with k = 0. 3. The reaction has an activation energy of 20 kJ mol-1 and an enthalpy of activation at 25 degrees C of 18 kJ mol-1 both above and below pH 7.45. It is suggested that O2- may reduce cytochrome c through a track composed of aromatic amino acids, and that little protein rearrangement is required for the formation of the activated complex. 4. No reduction of ferricytochrome c by HO2 radicals could be demonstrated at pH 1.2-6.2 but at pH 5.3, HO2 radicals oxidize ferrocytochrome c with a rate constant of about 5-10(5)-5-10(6) M-1 - S-1.", "contents": "The reaction between the superoxide anion radical and cytochrome c. 1. The superoxide anion radical (O2-) reacts with ferricytochrome c to form ferrocytochrome c. No intermediate complexes are observable. No reaction could be detected between O2- and ferrocytochrome c. 2. At 20 degrees C the rate constant for the reaction at pH 4.7 to 6.7 is 1.4-10(6) M-1. S -1 and as the pH increases above 6.7 the rate constant steadily decreases. The dependence on pH is the same for tuna heart and horse heart cytochrome c. No reaction could be demonstrated between O2- and the form of cytochrome c which exists above pH approximately 9.2. The dependence of the rate constant on pH can be explained if cytochrome c has pKs of 7.45 and 9.2, and O2- reacts with the form present below pH 7.45 with k = 1.4-10(6) M-1 - S-1, the form above pH 7.45 with k = 3.0- 10(5) M-1 - S-1, and the form present above pH 9.2 with k = 0. 3. The reaction has an activation energy of 20 kJ mol-1 and an enthalpy of activation at 25 degrees C of 18 kJ mol-1 both above and below pH 7.45. It is suggested that O2- may reduce cytochrome c through a track composed of aromatic amino acids, and that little protein rearrangement is required for the formation of the activated complex. 4. No reduction of ferricytochrome c by HO2 radicals could be demonstrated at pH 1.2-6.2 but at pH 5.3, HO2 radicals oxidize ferrocytochrome c with a rate constant of about 5-10(5)-5-10(6) M-1 - S-1."}
{"id": "PMID:61", "title": "Identification of the 120 mus phase in the decay of delayed fluorescence in spinach chloroplasts and subchloroplast particles as the intrinsic back reaction. The dependence of the level of this phase on the thylakoids internal pH.", "content": "After a 500 mus laser flash a 120 mus phase in the decay of delayed fluorescence is visible under a variety of circumstances in spinach chloroplasts and subchloroplast particles enriched in Photosystem II prepared by means of digitonin. The level of this phase is high in the case of inhibition of oxygen evolution at the donor side of Photosystem II. Comparison with the results of Babcock and Sauer (1975) Biochim. Bio-phys. Acta 376, 329-344, indicates that their EPR signal IIf which they suppose to be due to Z+, the oxidized first secondary donor of Photosystem II, is well correlated with a large amplitude of our 120 mus phase. We explain our 120 mus phase by the intrinsic back reaction of the excited reaction center in the presence of Z+, as predicted by Van Gorkom and Donze (1973) Photochem. Photobiol. 17, 333-342. The redox state of Z+ is dependent on the internal pH of the thylakoids. The results on the effect of pH in the mus region are compared with those obtained in the ms region.", "contents": "Identification of the 120 mus phase in the decay of delayed fluorescence in spinach chloroplasts and subchloroplast particles as the intrinsic back reaction. The dependence of the level of this phase on the thylakoids internal pH. After a 500 mus laser flash a 120 mus phase in the decay of delayed fluorescence is visible under a variety of circumstances in spinach chloroplasts and subchloroplast particles enriched in Photosystem II prepared by means of digitonin. The level of this phase is high in the case of inhibition of oxygen evolution at the donor side of Photosystem II. Comparison with the results of Babcock and Sauer (1975) Biochim. Bio-phys. Acta 376, 329-344, indicates that their EPR signal IIf which they suppose to be due to Z+, the oxidized first secondary donor of Photosystem II, is well correlated with a large amplitude of our 120 mus phase. We explain our 120 mus phase by the intrinsic back reaction of the excited reaction center in the presence of Z+, as predicted by Van Gorkom and Donze (1973) Photochem. Photobiol. 17, 333-342. The redox state of Z+ is dependent on the internal pH of the thylakoids. The results on the effect of pH in the mus region are compared with those obtained in the ms region."}
{"id": "PMID:62", "title": "Light-induced changes of absorbance and electron spin resonance in small photosystem II particles.", "content": "Photosystem II reaction center components have been studied in small system II particles prepared with digitonin. Upon illumination the reduction of the primary acceptor was indicated by absorbance changes due to the reduction of a plastoquinone to the semiquinone anion and by a small blue shifts of absorption bands near 545 nm (C550) and 685 nm. The semiquinone to chlorophyll ratio was between 1/20 and 1/70 in various preparations. The terminal electron donor in this reaction did not cause large absorbance changes but its oxidized form was revealed by a hitherto unknown electron spin resonance (ESR) signal, which had some properties of the well-known signal II but a linewidth and g-value much nearer to those of signal I. Upon darkening absorbance and ESR changes decayed together in a cyclic or back reaction which was stimulated by 3-(3,4 dichlorophenyl)-1,1-dimethylurea. The donor could be oxidized by ferricyanide in the dark. Illumination in the presence of ferricyanide induced absorbance and ESR changes, rapidly reversed upon darkening, which may be ascribed to the oxidation of a chlorophyll a dimer, possibly the primary electron donor of photosystem II. In addition an ESR signal with 15 to 20 gauss linewidth and a slower dark decay was observed, which may have been caused by a secondary donor.", "contents": "Light-induced changes of absorbance and electron spin resonance in small photosystem II particles. Photosystem II reaction center components have been studied in small system II particles prepared with digitonin. Upon illumination the reduction of the primary acceptor was indicated by absorbance changes due to the reduction of a plastoquinone to the semiquinone anion and by a small blue shifts of absorption bands near 545 nm (C550) and 685 nm. The semiquinone to chlorophyll ratio was between 1/20 and 1/70 in various preparations. The terminal electron donor in this reaction did not cause large absorbance changes but its oxidized form was revealed by a hitherto unknown electron spin resonance (ESR) signal, which had some properties of the well-known signal II but a linewidth and g-value much nearer to those of signal I. Upon darkening absorbance and ESR changes decayed together in a cyclic or back reaction which was stimulated by 3-(3,4 dichlorophenyl)-1,1-dimethylurea. The donor could be oxidized by ferricyanide in the dark. Illumination in the presence of ferricyanide induced absorbance and ESR changes, rapidly reversed upon darkening, which may be ascribed to the oxidation of a chlorophyll a dimer, possibly the primary electron donor of photosystem II. In addition an ESR signal with 15 to 20 gauss linewidth and a slower dark decay was observed, which may have been caused by a secondary donor."}
{"id": "PMID:63", "title": "Enzymic reactions of fatty acid hydroperoxides in extracts of potato tuber. II. Conversion of 9- and 13-hydroperoxy-octadecadienoic acids to monohydroxydienoic acid, epoxyhydroxy- and trihydroxymonoenoic acid derivatives.", "content": "1. Crude extracts and partially purified enzyme preparations from potato tubers catalyse, at pH 5-7, the conversion of linoleic acid hydroperoxides to a range of oxygenated fatty acid derivatives. 2. 9-D- and 13-L-hydroperoxide isomers are converted at similar rates to equivalent (isomeric) products. 3. The major products from the 13-hydroperoxide isomer were identified as the corresponding monohydroxydienoic acid derivative, threo-11-hydroxy-trans12,13-epoxy-octadec-cis9-enoic acid and 9,12,13-trihydroxy-octadec-trans10-enoic acid. The corresponding products from the 9-hydroperoxide were the monohydroxydienoic acid, 9,10-epoxy-11-hydroxy-octadec-12-enoic acid and 9,10,13-trihydroxy-octadec-11-enoic acid. 4. No separation of activities forming the different products was achieved by partial purification of enzyme extracts. 5. Product formation was unaffected by EDTA, CN-, sulphydryl reagents or glutathione but was reduced by boiling the extracts. 6. This system is compared with the 9-hydroperoxide-specific enzymic formation of divinyl ether derivatives by potato extracts.", "contents": "Enzymic reactions of fatty acid hydroperoxides in extracts of potato tuber. II. Conversion of 9- and 13-hydroperoxy-octadecadienoic acids to monohydroxydienoic acid, epoxyhydroxy- and trihydroxymonoenoic acid derivatives. 1. Crude extracts and partially purified enzyme preparations from potato tubers catalyse, at pH 5-7, the conversion of linoleic acid hydroperoxides to a range of oxygenated fatty acid derivatives. 2. 9-D- and 13-L-hydroperoxide isomers are converted at similar rates to equivalent (isomeric) products. 3. The major products from the 13-hydroperoxide isomer were identified as the corresponding monohydroxydienoic acid derivative, threo-11-hydroxy-trans12,13-epoxy-octadec-cis9-enoic acid and 9,12,13-trihydroxy-octadec-trans10-enoic acid. The corresponding products from the 9-hydroperoxide were the monohydroxydienoic acid, 9,10-epoxy-11-hydroxy-octadec-12-enoic acid and 9,10,13-trihydroxy-octadec-11-enoic acid. 4. No separation of activities forming the different products was achieved by partial purification of enzyme extracts. 5. Product formation was unaffected by EDTA, CN-, sulphydryl reagents or glutathione but was reduced by boiling the extracts. 6. This system is compared with the 9-hydroperoxide-specific enzymic formation of divinyl ether derivatives by potato extracts."}
{"id": "PMID:64", "title": "Partial purification and properties of microsomal phosphatidate phosphohydrolase from rat liver.", "content": "Microsomal phosphatidate phosphohydrolase (phosphatidate phosphatase EC 3.1.3.4) was solubilized and fractionated to yield at least two distinct enzymatically active fractions. One, denoted FA, was non-specific, had a relatively high Km for phosphatidic acid and was insensitive to inhibition by diacylglycerol. The second fraction, FB, was specific for phosphatidates, had a low Km, and was inhibited, non-competitively, by diacylglycerol. FA exhibited a sigmoid substrate-activity curve. The isolated FB aggregated to particles of about 10(6) in the absence of salts and could be dissociated by the addition of monovalent cations at ionic strength 0.4-0.6 to about 2-10(5) daltons and thereby doubled its activity. Dissociation was time- and temperature-dependent. F- was inhibitory. Divalent ions were not required for the activity of FA or FB and inhibited at concentrations exceeding 1 mM.", "contents": "Partial purification and properties of microsomal phosphatidate phosphohydrolase from rat liver. Microsomal phosphatidate phosphohydrolase (phosphatidate phosphatase EC 3.1.3.4) was solubilized and fractionated to yield at least two distinct enzymatically active fractions. One, denoted FA, was non-specific, had a relatively high Km for phosphatidic acid and was insensitive to inhibition by diacylglycerol. The second fraction, FB, was specific for phosphatidates, had a low Km, and was inhibited, non-competitively, by diacylglycerol. FA exhibited a sigmoid substrate-activity curve. The isolated FB aggregated to particles of about 10(6) in the absence of salts and could be dissociated by the addition of monovalent cations at ionic strength 0.4-0.6 to about 2-10(5) daltons and thereby doubled its activity. Dissociation was time- and temperature-dependent. F- was inhibitory. Divalent ions were not required for the activity of FA or FB and inhibited at concentrations exceeding 1 mM."}
{"id": "PMID:65", "title": "Bile acids. XLVII. 12alpha-Hydroxylation of precursors of allo bile acids by rabbit liver microsomes.", "content": "Rabbit liver microsomal preparations fortified with 0.1 mM NADPH effectively promote hydroxylation of [3beta-3H]- or [24-14C]allochenodeoxycholic acid or [5alpha,6alpha-3H2]5alpha-cholestane-3alpha,7alpha-diol to their respective 12alpha-hydroxyl derivatives in yields of about 25 or 65% in 60 min. Minor amounts of other products are formed from the diol. The requirements for activity of rabbit liver microsomal 12alpha-hydroxylase resemble those of rat liver microsomes. Of a number of enzyme inhibitors studied only p-chloromercuribenzoate demonstrated a marked ability to inhibit the reaction with either tritiated substrate. There was no difference in the quantity of product produced from the tritiated acid or the 14C-labeled acid. No clear sex difference was found in activity of the enzyme, nor was an appreciable difference noted in activity of the enzyme between mature and immature animals.", "contents": "Bile acids. XLVII. 12alpha-Hydroxylation of precursors of allo bile acids by rabbit liver microsomes. Rabbit liver microsomal preparations fortified with 0.1 mM NADPH effectively promote hydroxylation of [3beta-3H]- or [24-14C]allochenodeoxycholic acid or [5alpha,6alpha-3H2]5alpha-cholestane-3alpha,7alpha-diol to their respective 12alpha-hydroxyl derivatives in yields of about 25 or 65% in 60 min. Minor amounts of other products are formed from the diol. The requirements for activity of rabbit liver microsomal 12alpha-hydroxylase resemble those of rat liver microsomes. Of a number of enzyme inhibitors studied only p-chloromercuribenzoate demonstrated a marked ability to inhibit the reaction with either tritiated substrate. There was no difference in the quantity of product produced from the tritiated acid or the 14C-labeled acid. No clear sex difference was found in activity of the enzyme, nor was an appreciable difference noted in activity of the enzyme between mature and immature animals."}
{"id": "PMID:66", "title": "Partial purification and properties of a phenobarbital-induced aldehyde dehydrogenase of rat liver.", "content": "Properties of the phenobarbital induced cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) have been studied in rat liver. 7-12-Fold higher levels were seen in the cytoplasmic activities after phenobarbital treatment in reactor compared to non-reactor animals with high concentrations of acetaldehyde (18 mM) and propionaldehyde (9 mM). No difference was found with 0.12 mM acetaldehyde, 2 mM glycolaldehyde, 6 mM formaldehyde or 0.5 mM betaine aldehyde. The reactor group also had slightly higher activity in the mitochondrial fraction with the high acetaldehyde and propionaldehyde concentrations. In the microsomal fraction, the activities showed no differences at any substrate concentration. An induced aldehyde dehydrogenase was purified 70-fold by chromatographic techniques. It had different molecular and enzymic properties than the main high-Km enzyme normally present in rat liver cytoplasm. The pI of the induced enzyme was about 7.0 as measured by isoelectric focusing. It was active with several aliphatic and aromatic aldehydes but not with formaldehyde, glycolaldehyde or D-glyceraldehyde. The Km-values for propionaldehyde and acetaldehyde were in the millimolar range. Millimolar concentrations of aromatic aldehydes caused a strong substrate inhibition. The enzyme was inhibited by submicromolar concentrations of disulfiram. Estrone, deoxycorticosterone, progesterone and diethylstilbestrol also affected the enzyme activity.", "contents": "Partial purification and properties of a phenobarbital-induced aldehyde dehydrogenase of rat liver. Properties of the phenobarbital induced cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) have been studied in rat liver. 7-12-Fold higher levels were seen in the cytoplasmic activities after phenobarbital treatment in reactor compared to non-reactor animals with high concentrations of acetaldehyde (18 mM) and propionaldehyde (9 mM). No difference was found with 0.12 mM acetaldehyde, 2 mM glycolaldehyde, 6 mM formaldehyde or 0.5 mM betaine aldehyde. The reactor group also had slightly higher activity in the mitochondrial fraction with the high acetaldehyde and propionaldehyde concentrations. In the microsomal fraction, the activities showed no differences at any substrate concentration. An induced aldehyde dehydrogenase was purified 70-fold by chromatographic techniques. It had different molecular and enzymic properties than the main high-Km enzyme normally present in rat liver cytoplasm. The pI of the induced enzyme was about 7.0 as measured by isoelectric focusing. It was active with several aliphatic and aromatic aldehydes but not with formaldehyde, glycolaldehyde or D-glyceraldehyde. The Km-values for propionaldehyde and acetaldehyde were in the millimolar range. Millimolar concentrations of aromatic aldehydes caused a strong substrate inhibition. The enzyme was inhibited by submicromolar concentrations of disulfiram. Estrone, deoxycorticosterone, progesterone and diethylstilbestrol also affected the enzyme activity."}
{"id": "PMID:67", "title": "Cholinesterases from plant tissues. VI. Preliminary characterization of enzymes from Solanum melongena L. and Zea mays L.", "content": "Enzymes capable of hydrolyzing esters of thiocholine have been assayed in extracts of Solanum melongena L. (eggplant) and Zea Mays L. (corn). The enzymes from both species are inhibited by the anti-cholinesterases neostigmine, physostigmine, and 284c51 and by AMO-1618, a plant growth retardant and they both have pH optima near pH 8.0. The enzyme from eggplant is maximally active at a substrate concentration of 0.15 mM acetylthiocholine and is inhibited at higher substrate concentrations. On the basis of this last property, the magnitude of inhibition by the various inhibitors, and the substrate specificity, we conclude that the enzyme from eggplant, but not that from corn, is a cholinesterase.", "contents": "Cholinesterases from plant tissues. VI. Preliminary characterization of enzymes from Solanum melongena L. and Zea mays L. Enzymes capable of hydrolyzing esters of thiocholine have been assayed in extracts of Solanum melongena L. (eggplant) and Zea Mays L. (corn). The enzymes from both species are inhibited by the anti-cholinesterases neostigmine, physostigmine, and 284c51 and by AMO-1618, a plant growth retardant and they both have pH optima near pH 8.0. The enzyme from eggplant is maximally active at a substrate concentration of 0.15 mM acetylthiocholine and is inhibited at higher substrate concentrations. On the basis of this last property, the magnitude of inhibition by the various inhibitors, and the substrate specificity, we conclude that the enzyme from eggplant, but not that from corn, is a cholinesterase."}
{"id": "PMID:68", "title": "Behavior of soluble and immobilized acid phosphatase in hydro-organic media.", "content": "The hydrolysis of p-nitrophenyl phosphate by wheat germ acid phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.2) has been investigated in mixtures of aqueous buffers with acetone, dioxane and acetonitrile. The enzyme was either in free solution or immobilized on a pellicular support which consisted of a porous carbonaceous layer on solid glass beads. The highest enzyme activity was obtained in acetone and acetonitrile mixed with citrate buffer over a wide range of organic solvent concentration. In 50% (v/v) acetone both V and Km of the immobilized enzyme were about half of the values in the neat aqueous buffer, but the Ki for inorganic phosphate was unchanged. In 50% (v/v) mixtures of various solvents and citrate buffers of different pH, the enzymic activity was found to depend on the pH of the aqueous buffer component rather than the pH of the hydro-organic mixture as measured with the glass-calomel electrode. The relatively high rates of p-nitrophenol liberation in the presence of glucose even at high organic solvent concentrations suggest that transphosphorylation is facilitated at low water activity.", "contents": "Behavior of soluble and immobilized acid phosphatase in hydro-organic media. The hydrolysis of p-nitrophenyl phosphate by wheat germ acid phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.2) has been investigated in mixtures of aqueous buffers with acetone, dioxane and acetonitrile. The enzyme was either in free solution or immobilized on a pellicular support which consisted of a porous carbonaceous layer on solid glass beads. The highest enzyme activity was obtained in acetone and acetonitrile mixed with citrate buffer over a wide range of organic solvent concentration. In 50% (v/v) acetone both V and Km of the immobilized enzyme were about half of the values in the neat aqueous buffer, but the Ki for inorganic phosphate was unchanged. In 50% (v/v) mixtures of various solvents and citrate buffers of different pH, the enzymic activity was found to depend on the pH of the aqueous buffer component rather than the pH of the hydro-organic mixture as measured with the glass-calomel electrode. The relatively high rates of p-nitrophenol liberation in the presence of glucose even at high organic solvent concentrations suggest that transphosphorylation is facilitated at low water activity."}
{"id": "PMID:69", "title": "Purification and some enzymatic properties of the chitosanase from Bacillus R-4 which lyses Rhizopus cell walls.", "content": "A strain of Bacillus sp (Bacillus R-4) produces a protease and a carbohydrolase both of which have the ability to lyse Rhizopus cell walls. Of the enzymes, the carbohydrolase has been purified to an ultracentrifugally and electrophoretically homogeneous state, and identified as a chitosanase. The enzyme was active on glycol chitosan as well as chitosan. Molecular weight of the purified enzyme was estimated as 31 000 and isoelectric point as pH 8.30. The enzyme was most active at pH 5.6 and at 40 degrees C with either Rhizopus cell wall or glycol chitosan as substrate, and was stable over a range of pH 4.5 to 7.5 at 40 degrees C for 3 h. The activity was lost by sulfhydryl reagents and restored by either reduced glutathione of L-cysteine. An abrupt decrease in viscosity of the reaction mixture suggested an endowise cleavage of chitosan by this enzyme.", "contents": "Purification and some enzymatic properties of the chitosanase from Bacillus R-4 which lyses Rhizopus cell walls. A strain of Bacillus sp (Bacillus R-4) produces a protease and a carbohydrolase both of which have the ability to lyse Rhizopus cell walls. Of the enzymes, the carbohydrolase has been purified to an ultracentrifugally and electrophoretically homogeneous state, and identified as a chitosanase. The enzyme was active on glycol chitosan as well as chitosan. Molecular weight of the purified enzyme was estimated as 31 000 and isoelectric point as pH 8.30. The enzyme was most active at pH 5.6 and at 40 degrees C with either Rhizopus cell wall or glycol chitosan as substrate, and was stable over a range of pH 4.5 to 7.5 at 40 degrees C for 3 h. The activity was lost by sulfhydryl reagents and restored by either reduced glutathione of L-cysteine. An abrupt decrease in viscosity of the reaction mixture suggested an endowise cleavage of chitosan by this enzyme."}
{"id": "PMID:70", "title": "Specificity studies on alpha-mannosidases using oligosaccharides from mannosidosis urine as substrates.", "content": "Oligosaccharides containing terminal non-reducing alpha(1 leads to 2)-, alpha(1 leads to 3)-, and alpha(1 leads to 6)-linked mannose residues, isolated from human and bovine mannosidosis urines were used as substrates to test the specificities of acidic alpha-mannosidases isolated from human and bovine liver. The enzymes released all the alpha-linked mannose residues from each oligosaccharide and were most effective on the smallest substrate. Enzyme A in each case was less active on the oligosaccharides than alpha-mannosidase B2, even though the apparent Km value for the substrates was the same with each enzyme. The human acidic alpha-mannosidases were also found to be more active on substrates isolated from human rather than bovine mannosidosis urine. Human alpha-mannosidase C, which has a neutral pH optimum when assayed with a synthetic substrate, did not hydrolyse any of the oligosaccharides at neutral pH, but was found to be active at an acidic pH.", "contents": "Specificity studies on alpha-mannosidases using oligosaccharides from mannosidosis urine as substrates. Oligosaccharides containing terminal non-reducing alpha(1 leads to 2)-, alpha(1 leads to 3)-, and alpha(1 leads to 6)-linked mannose residues, isolated from human and bovine mannosidosis urines were used as substrates to test the specificities of acidic alpha-mannosidases isolated from human and bovine liver. The enzymes released all the alpha-linked mannose residues from each oligosaccharide and were most effective on the smallest substrate. Enzyme A in each case was less active on the oligosaccharides than alpha-mannosidase B2, even though the apparent Km value for the substrates was the same with each enzyme. The human acidic alpha-mannosidases were also found to be more active on substrates isolated from human rather than bovine mannosidosis urine. Human alpha-mannosidase C, which has a neutral pH optimum when assayed with a synthetic substrate, did not hydrolyse any of the oligosaccharides at neutral pH, but was found to be active at an acidic pH."}
{"id": "PMID:71", "title": "Calcium-stimulated adenosine triphosphatase in the microsomal fraction of tooth germ from porcine fetus.", "content": "The characterization and localization of a Ca(2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) in the tooth germ of the porcine fetus are reported. This enzyme, a microsome fraction, is preferentially activated by Ca(2+). In the presence of 0.5 mM ATP, maximal enzyme activity is obtained at 0.5--1.0 mM CaCl2. The maximal rate of ATP hydrolysis is approx. 20 mumol per h per mg of protein as the enzyme preparation is used here. At optimal Ca(2+) concentration, the Mg(2+) has an inhibitory effect. The enzyme does not require Na+ or/and K+ for activation by Ca(2+). Other nucleotide triphosphates may serve as the substrate, but V for ATP is the highest. The Km for ATP is 8.85 - 10(-5) M. The optimal pH for Ca(2+) activation of the enzyme lies around 9.2. Well known inhibitors of (Na+ + K+)-ATPase, mitochondria ATPase and Ca(2+)-ATPase in the erthrocyte do not inhibit the enzyme. In the subcellular order the enzyme may be assumed to be localized in the smooth endoplasmic reticulum fraction containing cell and Golgi body membrane fragments and in the tissue order in the enamel organ containing an ameloblast layer, stratum intermedium and stellate reticulum.", "contents": "Calcium-stimulated adenosine triphosphatase in the microsomal fraction of tooth germ from porcine fetus. The characterization and localization of a Ca(2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) in the tooth germ of the porcine fetus are reported. This enzyme, a microsome fraction, is preferentially activated by Ca(2+). In the presence of 0.5 mM ATP, maximal enzyme activity is obtained at 0.5--1.0 mM CaCl2. The maximal rate of ATP hydrolysis is approx. 20 mumol per h per mg of protein as the enzyme preparation is used here. At optimal Ca(2+) concentration, the Mg(2+) has an inhibitory effect. The enzyme does not require Na+ or/and K+ for activation by Ca(2+). Other nucleotide triphosphates may serve as the substrate, but V for ATP is the highest. The Km for ATP is 8.85 - 10(-5) M. The optimal pH for Ca(2+) activation of the enzyme lies around 9.2. Well known inhibitors of (Na+ + K+)-ATPase, mitochondria ATPase and Ca(2+)-ATPase in the erthrocyte do not inhibit the enzyme. In the subcellular order the enzyme may be assumed to be localized in the smooth endoplasmic reticulum fraction containing cell and Golgi body membrane fragments and in the tissue order in the enamel organ containing an ameloblast layer, stratum intermedium and stellate reticulum."}
{"id": "PMID:72", "title": "Preparation and characterization of an enzymatically active immobilized derivative of myosin.", "content": "Purified skeletal muscle myosin (EC 3.6.1.3) has been covalently bound to Sepharose 4B by the cyanogen bromide procedure. The resulting complex, Sepharose-Myosin, possesses adenosine triphosphatase activity and is relatively stable for long periods of time. Under optimal binding conditions, approximately 33% of the specific ATPase activity of the bound myosin is retained. Polyacrylamide gel electrophoresis of polypeptides released from denatured Sepharose-Myosin indicates that 85% of the myosin is attached to the agarose beads through the heavy chains and the remainder through the light chains, in agreement with predictions of binding and release based upon either the lysine contents or molecular weights of themyosin subunits. The adenosine triphosphatase of the immobilized myosin has been investigated under conditions of varying pH, ionic strength, and cation concentration. The ATPase profiles of immobilized myosin are quite similar to those for free myosin, however subtle differences are found. The Sepharose-Myosin ATPase is not as sensitive as myosin to alterations in salt concentration and the apparent KM is approximately two-fold higher than that of myosin. These differences are probably due to chemical modification in the region of the attachment site(s) to the agarose beads and hydration and diffusion limitations imposed by the polymeric agarose matrix.", "contents": "Preparation and characterization of an enzymatically active immobilized derivative of myosin. Purified skeletal muscle myosin (EC 3.6.1.3) has been covalently bound to Sepharose 4B by the cyanogen bromide procedure. The resulting complex, Sepharose-Myosin, possesses adenosine triphosphatase activity and is relatively stable for long periods of time. Under optimal binding conditions, approximately 33% of the specific ATPase activity of the bound myosin is retained. Polyacrylamide gel electrophoresis of polypeptides released from denatured Sepharose-Myosin indicates that 85% of the myosin is attached to the agarose beads through the heavy chains and the remainder through the light chains, in agreement with predictions of binding and release based upon either the lysine contents or molecular weights of themyosin subunits. The adenosine triphosphatase of the immobilized myosin has been investigated under conditions of varying pH, ionic strength, and cation concentration. The ATPase profiles of immobilized myosin are quite similar to those for free myosin, however subtle differences are found. The Sepharose-Myosin ATPase is not as sensitive as myosin to alterations in salt concentration and the apparent KM is approximately two-fold higher than that of myosin. These differences are probably due to chemical modification in the region of the attachment site(s) to the agarose beads and hydration and diffusion limitations imposed by the polymeric agarose matrix."}
{"id": "PMID:73", "title": "Radioactive labeling and location of specific thiol groups in myosin from fast, slow and cardiac muscles.", "content": "1. Based on incorporation of radioactively labeled N-ethylmaleimide, the readily reactive thiol groups of isolated myosin (EC 3.6.1.3) from fast, slow and cardiac muscles could be classified into 3 types. All 3 myosins contain 2 thiol-1, 2 thiol-2 and a variable number of thiol-3 groups per molecule. Both thiol-1 and thiol-2 groups which are essential for functioning of the K+-stimulated ATPase, are located in the heavy chains in all 3 myosin types. 2. The variation in the incorporation pattern of N-ethylmaleimide over the 3 thiol group classes under steady-state conditions of Mg(2+) - ATP hydrolysis allowed different conformations of some reaction intermediates to be characterized. In all 3 types of myosin the hydrolytic cycle of Mg(2+) - ATP was found to be controlled by the same step at 25 degrees C. In all three cases, this rate-limiting step is changed in the same way by lowereing temperature. 3. Using the chemically determined molecular weights for myosin light chains, their stoichiometry was found on the basis of sodium dodecyl sulfate electrophoresis to be 1.2 : 2.1 : 0.8 for light chain-1: light chain-2:light chain-3 per molecule of fast myosin, 2.0 : 1.9 for light chain-1:light chain-2 per molecule of slow myosin and 1.9 : 1.9 for light chain-1:light chain-2 per molecule of cardiac myosin. This qualitative difference in light subunit composition between the fast and the two types of slow myosin is not reflected in the small variations of the characteristics exhibited by the isolated myosins, but rather seems to be connected with their respective myofibrillar ATPase activities.", "contents": "Radioactive labeling and location of specific thiol groups in myosin from fast, slow and cardiac muscles. 1. Based on incorporation of radioactively labeled N-ethylmaleimide, the readily reactive thiol groups of isolated myosin (EC 3.6.1.3) from fast, slow and cardiac muscles could be classified into 3 types. All 3 myosins contain 2 thiol-1, 2 thiol-2 and a variable number of thiol-3 groups per molecule. Both thiol-1 and thiol-2 groups which are essential for functioning of the K+-stimulated ATPase, are located in the heavy chains in all 3 myosin types. 2. The variation in the incorporation pattern of N-ethylmaleimide over the 3 thiol group classes under steady-state conditions of Mg(2+) - ATP hydrolysis allowed different conformations of some reaction intermediates to be characterized. In all 3 types of myosin the hydrolytic cycle of Mg(2+) - ATP was found to be controlled by the same step at 25 degrees C. In all three cases, this rate-limiting step is changed in the same way by lowereing temperature. 3. Using the chemically determined molecular weights for myosin light chains, their stoichiometry was found on the basis of sodium dodecyl sulfate electrophoresis to be 1.2 : 2.1 : 0.8 for light chain-1: light chain-2:light chain-3 per molecule of fast myosin, 2.0 : 1.9 for light chain-1:light chain-2 per molecule of slow myosin and 1.9 : 1.9 for light chain-1:light chain-2 per molecule of cardiac myosin. This qualitative difference in light subunit composition between the fast and the two types of slow myosin is not reflected in the small variations of the characteristics exhibited by the isolated myosins, but rather seems to be connected with their respective myofibrillar ATPase activities."}
{"id": "PMID:74", "title": "Yeast glutathione reductase. Studies of the kinetics and stability of the enzyme as a function of pH and salt concentration.", "content": "1. The pH dependencies of the apparent Michaelis constant for oxidized glutathione and the apparent turnover number of yeast glutathione reductase (EC 1.6.4.2) have been determined at a fixed concentration of 0.1 mM NADPH in the range pH 4.5--8.0. Between pH 5.5 and 7.6, both of these parameters are relatively constant. The principal effect of low pH on the kinetics of the enzyme-catalyzed reaction is the observation of a pH-dependent substrate inhibition by oxidized glutathione at pH less than or equal 7, which is shown to correlate with the binding of oxidized glutathione to the oxidized form of the enzyme. 2. The catalytic activity of yeast glutathione reductase at pH 5.5 is affected by the sodium acetate buffer concentration. The stability of the oxidized and reduced forms of the enzyme at pH 5.5 and 25 degrees C in the absence of bovine serum albumin was studied as a function of sodium acetate concentration. The results show that activation of the catalytic activity of the enzyme at low sodium acetate concentration correlates with an effect of sodium acetate on a reduced form of the enzyme. In contrast, inhibition of the catalytic activity of the enzyme at high sodium acetate concentration correlates with an effect of sodium acetate on the oxidized form of the enzyme.", "contents": "Yeast glutathione reductase. Studies of the kinetics and stability of the enzyme as a function of pH and salt concentration. 1. The pH dependencies of the apparent Michaelis constant for oxidized glutathione and the apparent turnover number of yeast glutathione reductase (EC 1.6.4.2) have been determined at a fixed concentration of 0.1 mM NADPH in the range pH 4.5--8.0. Between pH 5.5 and 7.6, both of these parameters are relatively constant. The principal effect of low pH on the kinetics of the enzyme-catalyzed reaction is the observation of a pH-dependent substrate inhibition by oxidized glutathione at pH less than or equal 7, which is shown to correlate with the binding of oxidized glutathione to the oxidized form of the enzyme. 2. The catalytic activity of yeast glutathione reductase at pH 5.5 is affected by the sodium acetate buffer concentration. The stability of the oxidized and reduced forms of the enzyme at pH 5.5 and 25 degrees C in the absence of bovine serum albumin was studied as a function of sodium acetate concentration. The results show that activation of the catalytic activity of the enzyme at low sodium acetate concentration correlates with an effect of sodium acetate on a reduced form of the enzyme. In contrast, inhibition of the catalytic activity of the enzyme at high sodium acetate concentration correlates with an effect of sodium acetate on the oxidized form of the enzyme."}
{"id": "PMID:75", "title": "Characteristics of the dephosphorylated form of phosphorylase purified from rat liver and measurement of its activity in crude liver preparations.", "content": "The phosphorylated form of liver glycogen phosphorylase (alpha-1,4-glucan : orthophosphate alpha-glucosyl-transferase, EC 2.4.1.1) (phosphorylase a) is active and easily measured while the dephosphorylated form (phosphorylase b), in contrast to the muscle enzyme, has been reported to be essentially inactive even in the presence of AMP. We have purified both forms of phosphorylase from rat liver and studied the characteristics of each. Phosphorylase b activity can be measured with our assay conditions. The phosphorylase b we obtained was stimulated by high concentrations of sulfate, and was a substrate for muscle phosphorylase kinase whereas phosphorylase a was inhibited by sulfate, and was a substrate for liver phosphorylase phosphatase. Substrate binding to phosphorylase b was poor (KM glycogen = 2.5 mM, glucose-1-P = 250 mM) compared to phosphorylase a (KM glycogen = 1.8 mM, KM glucose-1-P = 0.7 mM). Liver phosphorylase b was active in the absence of AMP. However, AMP lowered the KM for glucose-1-P to 80 mM for purified phosphorylase b and to 60 mM for the enzyme in crude extract (Ka = 0.5 mM). Using appropriate substrate, buffer and AMP concentrations, assay conditions have been developed which allow determination of phosphorylase a and 90% of the phosphorylase b activity in liver extracts. Interconversion of the two forms can be demonstrated in vivo (under acute stimulation) and in vitro with little change in total activity. A decrease in total phosphorylase activity has been observed after prolonged starvation and in diabetes.", "contents": "Characteristics of the dephosphorylated form of phosphorylase purified from rat liver and measurement of its activity in crude liver preparations. The phosphorylated form of liver glycogen phosphorylase (alpha-1,4-glucan : orthophosphate alpha-glucosyl-transferase, EC 2.4.1.1) (phosphorylase a) is active and easily measured while the dephosphorylated form (phosphorylase b), in contrast to the muscle enzyme, has been reported to be essentially inactive even in the presence of AMP. We have purified both forms of phosphorylase from rat liver and studied the characteristics of each. Phosphorylase b activity can be measured with our assay conditions. The phosphorylase b we obtained was stimulated by high concentrations of sulfate, and was a substrate for muscle phosphorylase kinase whereas phosphorylase a was inhibited by sulfate, and was a substrate for liver phosphorylase phosphatase. Substrate binding to phosphorylase b was poor (KM glycogen = 2.5 mM, glucose-1-P = 250 mM) compared to phosphorylase a (KM glycogen = 1.8 mM, KM glucose-1-P = 0.7 mM). Liver phosphorylase b was active in the absence of AMP. However, AMP lowered the KM for glucose-1-P to 80 mM for purified phosphorylase b and to 60 mM for the enzyme in crude extract (Ka = 0.5 mM). Using appropriate substrate, buffer and AMP concentrations, assay conditions have been developed which allow determination of phosphorylase a and 90% of the phosphorylase b activity in liver extracts. Interconversion of the two forms can be demonstrated in vivo (under acute stimulation) and in vitro with little change in total activity. A decrease in total phosphorylase activity has been observed after prolonged starvation and in diabetes."}
{"id": "PMID:76", "title": "Multiple forms of casein kinase from rabbit erythrocytes.", "content": "Two rabbit erythrocyte casein kinases, GTP:casein kinase I and GTP:casein kinase II, have been purified 29 000- and 47 000-fold, respectively. Studies employing sucrose density gradient centrifugation indicate that kinase I has a molecular weight of about 9.5 - 10(5) (25 S) and kinase II about 1.4 - 10(6) (32 S). These enzymes can utilize either ATP or GTP as the phosphoryl donor. Among various protein substrates examined, these kinases catalyze the phosphorylation of casein greater than 50% dephosphorylated phosvitin congruent to 50% dephosphorylated casein greater than phosvitin. Histones, protamine and bovine serum albumin are poor phosphoryl acceptors. Kinetic data indicate that both enzymes are inhibited by high casein substrate concentrations which may be partially relieved by NaCl. Both phosphotransferases require Mg(2+) for activity and are optimally active at pH 9.0. The enzymes have apparent Km values of 2.5 - 10(-5) M for GTP, 2 - 10(-5) M for ATP, and 0.4--0.6 mg/ml for casein. The incorporation of the terminal phosphate of GTP into casein as catalyzed by these enzymes is inhibited to varying degrees by ATP, ITP, ADP, and GDP but not by UTP, CTP, GMP, adenosine 3':5'-cyclic monophosphate, and guanosine 3':5'-cyclic monophosphate. In addition, NaF and 2,3-diphosphoglyceric acid are also found to inhibit the activity of both kinases. The effect of 2,3-diphosphoglycerate is interesting and suggests that this metabolite may regulate the activity of the casein kinases in the red blood cells.", "contents": "Multiple forms of casein kinase from rabbit erythrocytes. Two rabbit erythrocyte casein kinases, GTP:casein kinase I and GTP:casein kinase II, have been purified 29 000- and 47 000-fold, respectively. Studies employing sucrose density gradient centrifugation indicate that kinase I has a molecular weight of about 9.5 - 10(5) (25 S) and kinase II about 1.4 - 10(6) (32 S). These enzymes can utilize either ATP or GTP as the phosphoryl donor. Among various protein substrates examined, these kinases catalyze the phosphorylation of casein greater than 50% dephosphorylated phosvitin congruent to 50% dephosphorylated casein greater than phosvitin. Histones, protamine and bovine serum albumin are poor phosphoryl acceptors. Kinetic data indicate that both enzymes are inhibited by high casein substrate concentrations which may be partially relieved by NaCl. Both phosphotransferases require Mg(2+) for activity and are optimally active at pH 9.0. The enzymes have apparent Km values of 2.5 - 10(-5) M for GTP, 2 - 10(-5) M for ATP, and 0.4--0.6 mg/ml for casein. The incorporation of the terminal phosphate of GTP into casein as catalyzed by these enzymes is inhibited to varying degrees by ATP, ITP, ADP, and GDP but not by UTP, CTP, GMP, adenosine 3':5'-cyclic monophosphate, and guanosine 3':5'-cyclic monophosphate. In addition, NaF and 2,3-diphosphoglyceric acid are also found to inhibit the activity of both kinases. The effect of 2,3-diphosphoglycerate is interesting and suggests that this metabolite may regulate the activity of the casein kinases in the red blood cells."}
{"id": "PMID:77", "title": "Kinetic studies and effects of anions on creatine phosphokinase from skeletal muscle of rhesus monkey (Macaca mulatta).", "content": "A purification procedure for creatine kinase (EC 2.7.3.2) from muscle of the monke35--170 muequiv H+/mg protein per min at 30 degrees C and a yield of approx. 0.5 g/kg muscle. Assuming equilibrium kinetics, synergistic binding of substrates at one catalytic site is found for both the forward and back reactions. Kinetic constants for the binding of each substrate to the free enzyme and the enzyme-second substrate complex are determined and are compared with those for the enzyme from other species. Inhibition by small anions is determined in the presence of different combinations of substrates and products. SO4(2-) inhibits by simple competitive inhibition and probably binds at the site of the transferrable phosphoryl group. Inhibition by NO3-, NO2-, SCN- and Cl- is more complex and these ions are suggested to mimic the transferrable phosphoryl group in a planar transition-state complex. These anions stabilize the dead-end complex, enzyme-creatine-MgADP, which lacks the transferable phosphoryl group. The effects of these anions on the dissociation constants of the enzyme-substrate complexes is reported and is in accord with the above hypothesis. The dead-end complex in the absence of anion does not protect the essential thiol group against inhibition by iodoacetamide. Addition of NO3- or Cl- to the dead-end complex or a substrate equilibrium mixture without anion confers protection. The essential thiol group is inhibited by iodoacetamide at a rate which is essentially independent of pH over the normal stability range of the enzyme. Contrary to our previous report this pH independence is not altered by the presence of dead-end complex, creatine plus MgADP, in the presence or absence of anion or in the presence of a substrate equilibrium mixture. It is  inferred that the 'essential' thiol group of the monkey enzyme has essentially the same properties as that of the rabbit enzyme. In consequence, the inferences made about the role of this group based on our previous work on the monkey enzyme are no longer valid. The present findings are compatible with the essential thiol group playing a conformational role in the catalytic process.", "contents": "Kinetic studies and effects of anions on creatine phosphokinase from skeletal muscle of rhesus monkey (Macaca mulatta). A purification procedure for creatine kinase (EC 2.7.3.2) from muscle of the monke35--170 muequiv H+/mg protein per min at 30 degrees C and a yield of approx. 0.5 g/kg muscle. Assuming equilibrium kinetics, synergistic binding of substrates at one catalytic site is found for both the forward and back reactions. Kinetic constants for the binding of each substrate to the free enzyme and the enzyme-second substrate complex are determined and are compared with those for the enzyme from other species. Inhibition by small anions is determined in the presence of different combinations of substrates and products. SO4(2-) inhibits by simple competitive inhibition and probably binds at the site of the transferrable phosphoryl group. Inhibition by NO3-, NO2-, SCN- and Cl- is more complex and these ions are suggested to mimic the transferrable phosphoryl group in a planar transition-state complex. These anions stabilize the dead-end complex, enzyme-creatine-MgADP, which lacks the transferable phosphoryl group. The effects of these anions on the dissociation constants of the enzyme-substrate complexes is reported and is in accord with the above hypothesis. The dead-end complex in the absence of anion does not protect the essential thiol group against inhibition by iodoacetamide. Addition of NO3- or Cl- to the dead-end complex or a substrate equilibrium mixture without anion confers protection. The essential thiol group is inhibited by iodoacetamide at a rate which is essentially independent of pH over the normal stability range of the enzyme. Contrary to our previous report this pH independence is not altered by the presence of dead-end complex, creatine plus MgADP, in the presence or absence of anion or in the presence of a substrate equilibrium mixture. It is  inferred that the 'essential' thiol group of the monkey enzyme has essentially the same properties as that of the rabbit enzyme. In consequence, the inferences made about the role of this group based on our previous work on the monkey enzyme are no longer valid. The present findings are compatible with the essential thiol group playing a conformational role in the catalytic process."}
{"id": "PMID:78", "title": "Studies on rat renal cortical cell kallikrein. I. Separation and measurement.", "content": "A technique has been developed to separate and measure kallikrein in a heterogeneous population of rat renal cortical cells in suspension. After rat kidneys were perfused in situ in anaesthetized rats, viable, counted cortical cell suspensions were obtained. Cells were suspended in a sucrose/Tris buffer containing 0.5% deoxycholate, homogenized, centrifuged, dialyzed, and gel filtered on Sephadex G-25. Column chromatography on DEAE-cellulose resulted in a single peak of esterase activity between 0.20 to 0.25 M NaCl/sodium phosphate buffer. Subsequent elution yielded an alkaline esterase which was identical to kallikrein isolated from rat urine, insofar as pH optimum, effects of inhibitors, bioassay activity and immunological properties were concerned. Calculated yields were about 70% of the total esterase activity present in the parent cell homogenates. Recoveries of a purified rat urinary kallikrein added to the cell homogenates, the DEAE-cellulose columns, or the eluates from the columns ranged from 83-108% (mean 96%). Using this technique, it was found that the amount of kallikrein activity present in non-incubated renal cortical cells ranged from 0.6-10(-2) to 4.6 - 10(-2) alpha-N-tosyl-L-arginine methyl ester (Tos-Arg-OMe) esterase units per 10(8) cells. However, cells incubated in a nutrient medium at 37 degrees C for 3-8 h contained no measurable kallikrein activity, whereas the surrounding medium had kallikrein activity which could be significantly increased by aldosterone and decreased by spironolactone.", "contents": "Studies on rat renal cortical cell kallikrein. I. Separation and measurement. A technique has been developed to separate and measure kallikrein in a heterogeneous population of rat renal cortical cells in suspension. After rat kidneys were perfused in situ in anaesthetized rats, viable, counted cortical cell suspensions were obtained. Cells were suspended in a sucrose/Tris buffer containing 0.5% deoxycholate, homogenized, centrifuged, dialyzed, and gel filtered on Sephadex G-25. Column chromatography on DEAE-cellulose resulted in a single peak of esterase activity between 0.20 to 0.25 M NaCl/sodium phosphate buffer. Subsequent elution yielded an alkaline esterase which was identical to kallikrein isolated from rat urine, insofar as pH optimum, effects of inhibitors, bioassay activity and immunological properties were concerned. Calculated yields were about 70% of the total esterase activity present in the parent cell homogenates. Recoveries of a purified rat urinary kallikrein added to the cell homogenates, the DEAE-cellulose columns, or the eluates from the columns ranged from 83-108% (mean 96%). Using this technique, it was found that the amount of kallikrein activity present in non-incubated renal cortical cells ranged from 0.6-10(-2) to 4.6 - 10(-2) alpha-N-tosyl-L-arginine methyl ester (Tos-Arg-OMe) esterase units per 10(8) cells. However, cells incubated in a nutrient medium at 37 degrees C for 3-8 h contained no measurable kallikrein activity, whereas the surrounding medium had kallikrein activity which could be significantly increased by aldosterone and decreased by spironolactone."}
{"id": "PMID:79", "title": "Studies on electron transfer between mercury electrode and hemoprotein.", "content": "The electrochemical behaviour of ferricytochrome c, metmyoglobin and methemoglobin was studied using d.c., a.c. and differential pulse polarography, and controlled potential electrolysis. 1. The three hemoproteins yield d.c. polarographic steps, and peaks in differential pulse polarograms, the height of which is proportional to concentration. The charge transfer is influenced by strong adsorption. 2. The concentration dependence of the a.c. polarograms indicates structural changes in the adsorbed molecules. 3. The reduction products of controlled potential electrolysis of metmyoglobin and methemoglobin have absorption spectra identical with the native control samples. The affinity for oxygen and the cooperativity in hemoglobin are not affected by the reaction at the electrode. 4. The charge transfer proceeds via adsorbed, already reduced, molecules to freely diffusible proteins.", "contents": "Studies on electron transfer between mercury electrode and hemoprotein. The electrochemical behaviour of ferricytochrome c, metmyoglobin and methemoglobin was studied using d.c., a.c. and differential pulse polarography, and controlled potential electrolysis. 1. The three hemoproteins yield d.c. polarographic steps, and peaks in differential pulse polarograms, the height of which is proportional to concentration. The charge transfer is influenced by strong adsorption. 2. The concentration dependence of the a.c. polarograms indicates structural changes in the adsorbed molecules. 3. The reduction products of controlled potential electrolysis of metmyoglobin and methemoglobin have absorption spectra identical with the native control samples. The affinity for oxygen and the cooperativity in hemoglobin are not affected by the reaction at the electrode. 4. The charge transfer proceeds via adsorbed, already reduced, molecules to freely diffusible proteins."}
{"id": "PMID:80", "title": "The binding of organic phosphates to human methaemoglobin A. Perturbation of the polymerization of proteins by effectors.", "content": "Theory is presented relating to the binding of an effector to two states of a protein acceptor coexisting in equilibrium. The problem is treated in terms of the four possible cases which specify relations between numbers of binding sites and intrinsic binding constants relevant to the acceptor states. It is shown that a distinction between these cases may be possible on the basis of the form of a plot of unbound effector concentration versus the constituent equilibrium coefficient which may be calculated from the sedimentation coefficient of the protein constituent. Particularly noteworthy in this respect is the finding that a turning point may exist in this plot for defined conditions with systems in which binding sites are not conserved (and binding affinities are altered) on polymer formation. The latter type of system is exemplified by studies on methaemoglobin A in 0.25 M sodium acetate, pH 5.4. In the absence of added organic phosphate effectors, a dimer-tetramer equilibrium operates governed by an association constant of 4.15 +/- 0.06 X 10(3) 1/mol, determined from sedimentation equilibrium results. Correlation of sedimentation velocity and equilibrium results shows that addition of adenosine 5'-triphosphate (ATP) results in its binding to one site on each of the dimeric (alpha beta) and tetrameric (alpha beta)2 species with intrinsic binding constants 1.03-10(3)-1.20-10(3) and 1.1-10(4)-2.1-10(4) 1/mol, respectively. It is also shown that 2,3-diphosphoglycerate perturbs the dimer-tetramer equilibrium in a similar way to ATP.", "contents": "The binding of organic phosphates to human methaemoglobin A. Perturbation of the polymerization of proteins by effectors. Theory is presented relating to the binding of an effector to two states of a protein acceptor coexisting in equilibrium. The problem is treated in terms of the four possible cases which specify relations between numbers of binding sites and intrinsic binding constants relevant to the acceptor states. It is shown that a distinction between these cases may be possible on the basis of the form of a plot of unbound effector concentration versus the constituent equilibrium coefficient which may be calculated from the sedimentation coefficient of the protein constituent. Particularly noteworthy in this respect is the finding that a turning point may exist in this plot for defined conditions with systems in which binding sites are not conserved (and binding affinities are altered) on polymer formation. The latter type of system is exemplified by studies on methaemoglobin A in 0.25 M sodium acetate, pH 5.4. In the absence of added organic phosphate effectors, a dimer-tetramer equilibrium operates governed by an association constant of 4.15 +/- 0.06 X 10(3) 1/mol, determined from sedimentation equilibrium results. Correlation of sedimentation velocity and equilibrium results shows that addition of adenosine 5'-triphosphate (ATP) results in its binding to one site on each of the dimeric (alpha beta) and tetrameric (alpha beta)2 species with intrinsic binding constants 1.03-10(3)-1.20-10(3) and 1.1-10(4)-2.1-10(4) 1/mol, respectively. It is also shown that 2,3-diphosphoglycerate perturbs the dimer-tetramer equilibrium in a similar way to ATP."}
{"id": "PMID:81", "title": "N-terminal spin label studies of hemoglobin, Ligand and pH dependence.", "content": "Human hemoglobin was spin labeled with 4-isothiocanato-2,2,6,6-tetramethyl-piperdinooxyl, which is known to bind specifically to the N-terminal alpha-amino groups of proteins and slightly to the reactive sulfhydryl groups. Electron spin resonance (ESR) analysis indicated a partially resolved five-line spectrum, suggesting that the label was attached to at least two different binding sites. Using specific blocking reagents prior to spin labeling, the two binding sites were attributed to the sulfhydryl group of beta-93 (immobile) and the alpha-amino group of the N-terminal valines (mobile). The relative motion of the spin at one set of binding sites was restricted regardless of the state of ligation and pH, while the motion at the other site showed dependence on those parameters, e.g. the spin-labeled N-terminal ends of deoxyhemoglobin have restricted motion at all pH ranges studied, while those of oxyhemoglobin are relatively free to move at the basic pH range, but become more restricted in the acidic pH range.", "contents": "N-terminal spin label studies of hemoglobin, Ligand and pH dependence. Human hemoglobin was spin labeled with 4-isothiocanato-2,2,6,6-tetramethyl-piperdinooxyl, which is known to bind specifically to the N-terminal alpha-amino groups of proteins and slightly to the reactive sulfhydryl groups. Electron spin resonance (ESR) analysis indicated a partially resolved five-line spectrum, suggesting that the label was attached to at least two different binding sites. Using specific blocking reagents prior to spin labeling, the two binding sites were attributed to the sulfhydryl group of beta-93 (immobile) and the alpha-amino group of the N-terminal valines (mobile). The relative motion of the spin at one set of binding sites was restricted regardless of the state of ligation and pH, while the motion at the other site showed dependence on those parameters, e.g. the spin-labeled N-terminal ends of deoxyhemoglobin have restricted motion at all pH ranges studied, while those of oxyhemoglobin are relatively free to move at the basic pH range, but become more restricted in the acidic pH range."}
{"id": "PMID:82", "title": "The behavior of holo- and apo-forms of bovine superoxide dismutase at low pH.", "content": "1. Holo-superoxide dismutase from bovine erythrocytes has been shown to undergo a reversible structural modification in the pH 3-5 range. 2. The spectral alterations observed on changing from neutrality to pH 2 were: a slight attenuation of the 680 nm absorbance; the loss of the 450 nm shoulder, apparent in the optical spectrum of the native protein; and a new band appeared at 330 nm. The circular dichroism at 600 nm was essentially lost while a weak negative band appeared at approx. 380 nm and a positive band at 310 nm. 3. The EPR spectrum was also modified on changing from the native to the low pH form: A parallel increased from approximately 130 to approximately 150 G, g parallel remained unchanged at approximately 2.27, and gm decreased from approximately 2.09 to approximately 2.08. The apparent linewidth remained essentially constant. 4. High resolution (220 MHz) PMR spectra of holo- and apoproteins revealed that the metals influence the three-dimensional structure of the protein. 5. PMR studies indicated that at pH 3 the apoprotein existed almost entirely in a random coil form and that it assumed a compact well-ordered structure on returning to neutral pH. The holoprotein maintained a compact, apparently dimeric, structure even at pH 3.", "contents": "The behavior of holo- and apo-forms of bovine superoxide dismutase at low pH. 1. Holo-superoxide dismutase from bovine erythrocytes has been shown to undergo a reversible structural modification in the pH 3-5 range. 2. The spectral alterations observed on changing from neutrality to pH 2 were: a slight attenuation of the 680 nm absorbance; the loss of the 450 nm shoulder, apparent in the optical spectrum of the native protein; and a new band appeared at 330 nm. The circular dichroism at 600 nm was essentially lost while a weak negative band appeared at approx. 380 nm and a positive band at 310 nm. 3. The EPR spectrum was also modified on changing from the native to the low pH form: A parallel increased from approximately 130 to approximately 150 G, g parallel remained unchanged at approximately 2.27, and gm decreased from approximately 2.09 to approximately 2.08. The apparent linewidth remained essentially constant. 4. High resolution (220 MHz) PMR spectra of holo- and apoproteins revealed that the metals influence the three-dimensional structure of the protein. 5. PMR studies indicated that at pH 3 the apoprotein existed almost entirely in a random coil form and that it assumed a compact well-ordered structure on returning to neutral pH. The holoprotein maintained a compact, apparently dimeric, structure even at pH 3."}
{"id": "PMID:83", "title": "Mechanical precipitation of hemoglobin k\u00f6ln.", "content": "Hb K\u00f6ln (beta 98 Val leads to Met) was found to precipitate rapidly during mechanical shaking. The rate of precipitation of Hb K\u00f6ln is 5-6 times faster than that of Hb S. The kinetics of precipitation of the patient's hemolysate, which is a mixture of Hb K\u00f6ln and Hb A, showed a biphasic curve indicating that Hb K\u00f6ln precipitates independently from Hb A. The instability of Hb K\u00f6ln may be attributed to the conformational change in the vicinity of heme. The mechanical shaking may be used as a new method for detection and quantitation of hemoglobin K\u00f6ln and other unstable hemoglobins.", "contents": "Mechanical precipitation of hemoglobin k\u00f6ln. Hb K\u00f6ln (beta 98 Val leads to Met) was found to precipitate rapidly during mechanical shaking. The rate of precipitation of Hb K\u00f6ln is 5-6 times faster than that of Hb S. The kinetics of precipitation of the patient's hemolysate, which is a mixture of Hb K\u00f6ln and Hb A, showed a biphasic curve indicating that Hb K\u00f6ln precipitates independently from Hb A. The instability of Hb K\u00f6ln may be attributed to the conformational change in the vicinity of heme. The mechanical shaking may be used as a new method for detection and quantitation of hemoglobin K\u00f6ln and other unstable hemoglobins."}
{"id": "PMID:84", "title": "Physical properties and subunits of Haemopis grandis erythrocruorin.", "content": "The erythrocruorin of the leech Haemopis grandis possessed an S20,w of 57 S at neutral pH, its isoelectric point at pH 6.0 and exhibited a slightly sigmoid oxygenation curve with n approximately 2.1 and P50 = 11.2 mm at pH 7.4. A minimum molecular weight of 24000 +/- 1500 per heme group was determined from the iron and heme contents, 0.22 +/- 0.01 and 2.73 +/- 0.14 weight %, respectively. The subunit composition of the erythrocruorin was investigated using gel filtration in sodium dodecyl sulfate and polyacrylamide gel electrophoresis in sodium dodecyl sulfate at neutral pH. Haemopis erythrocruorin dissociated in the presence of sodium dodecyl sulfate into four subunits (1 through 4) possessing molecular weights of about 27000, 23000, 21000 and 13500, respectively. When the erythrocruorin was reduced with mercaptoethanol prior to sodium dodecyl sulfate electrophoresis, three subunits  were observed, possessing molecular weights of about 13000 (I), 16500 (II) and 28000 (III). Sodium dodecyl sulfate electrophoresis of the isolated subunits 1 through 4 showed that subunit I was provided by subunits 1 and 4, subunit II was provided by subunit 1 and subunit III was provided by both subunit 2 and subunit 3. Haemopis erythrocruorin thus appeared to consist of at least five different polypeptide chains. It is likely that not all of the constituent polypeptide chains were associated each with a heme group. The shape of the Haemopis erythrocruorin observed by electron microscopy appeared to be consistent with the two-tiered hexagonal array characteristic of annelid erythrocruorins and chlorocruorins.", "contents": "Physical properties and subunits of Haemopis grandis erythrocruorin. The erythrocruorin of the leech Haemopis grandis possessed an S20,w of 57 S at neutral pH, its isoelectric point at pH 6.0 and exhibited a slightly sigmoid oxygenation curve with n approximately 2.1 and P50 = 11.2 mm at pH 7.4. A minimum molecular weight of 24000 +/- 1500 per heme group was determined from the iron and heme contents, 0.22 +/- 0.01 and 2.73 +/- 0.14 weight %, respectively. The subunit composition of the erythrocruorin was investigated using gel filtration in sodium dodecyl sulfate and polyacrylamide gel electrophoresis in sodium dodecyl sulfate at neutral pH. Haemopis erythrocruorin dissociated in the presence of sodium dodecyl sulfate into four subunits (1 through 4) possessing molecular weights of about 27000, 23000, 21000 and 13500, respectively. When the erythrocruorin was reduced with mercaptoethanol prior to sodium dodecyl sulfate electrophoresis, three subunits  were observed, possessing molecular weights of about 13000 (I), 16500 (II) and 28000 (III). Sodium dodecyl sulfate electrophoresis of the isolated subunits 1 through 4 showed that subunit I was provided by subunits 1 and 4, subunit II was provided by subunit 1 and subunit III was provided by both subunit 2 and subunit 3. Haemopis erythrocruorin thus appeared to consist of at least five different polypeptide chains. It is likely that not all of the constituent polypeptide chains were associated each with a heme group. The shape of the Haemopis erythrocruorin observed by electron microscopy appeared to be consistent with the two-tiered hexagonal array characteristic of annelid erythrocruorins and chlorocruorins."}
{"id": "PMID:85", "title": "Myosin from arterial smooth muscle: isolation following actin depolymerization.", "content": "The contractile proteins from arterial smooth muscle are highly soluble, and can be extracted at I = 0.05. However, they can be precipitated by a prolonged dialysis at pH 6 to give an actomyosin with a high, although variable, actin:myosin ratio. The sedimentation behavior of this actomyosin at high ionic strength was examined as a function of pH, protein concentration and composition by preparative ultracentrifugation. Comparisons with synthetic skeletal muscle actomyosins of similar composition demonstrated significant differences in the behaviors of these two systems. It was found that much smooth muscle actomyosin is not dissociated by normally relaxing conditions, and that it sediments at a slower rate than F-actin. The solubility of the supernatant protein (a myosin-enriched actomyosin) in 0.2 M K Cl (pH 7) depended on the pH during centrifugation. A lower solubility was associated only with a higher actin concentration in the supernatant, suggesting a dependence on actin repolymerization. Pure myosin was selectively precipitated from the supernatant by polyethylene glycol-6000, but only when the protein was soluble at low ionic strength. The solubility of purified myosin was similar to that of myosin from striated muscles. A relationship between the presence of depolymerized actin and the high solubility of smooth muscle contractile proteins is suggested.", "contents": "Myosin from arterial smooth muscle: isolation following actin depolymerization. The contractile proteins from arterial smooth muscle are highly soluble, and can be extracted at I = 0.05. However, they can be precipitated by a prolonged dialysis at pH 6 to give an actomyosin with a high, although variable, actin:myosin ratio. The sedimentation behavior of this actomyosin at high ionic strength was examined as a function of pH, protein concentration and composition by preparative ultracentrifugation. Comparisons with synthetic skeletal muscle actomyosins of similar composition demonstrated significant differences in the behaviors of these two systems. It was found that much smooth muscle actomyosin is not dissociated by normally relaxing conditions, and that it sediments at a slower rate than F-actin. The solubility of the supernatant protein (a myosin-enriched actomyosin) in 0.2 M K Cl (pH 7) depended on the pH during centrifugation. A lower solubility was associated only with a higher actin concentration in the supernatant, suggesting a dependence on actin repolymerization. Pure myosin was selectively precipitated from the supernatant by polyethylene glycol-6000, but only when the protein was soluble at low ionic strength. The solubility of purified myosin was similar to that of myosin from striated muscles. A relationship between the presence of depolymerized actin and the high solubility of smooth muscle contractile proteins is suggested."}
{"id": "PMID:86", "title": "Hybrids of chemical derivatives of Escherichia coli alkaline phosphatase.", "content": "The activities of hybrid dimers of alkaline phosphatase containing two chemically modified subunits have been investigated. One hybrid species was prepared by dissociation and reconstitution of a mixture of two variants produced by chemical modification of the native enzyme with succinic anhydride and tetranitromethane, respectively. The succinyl-nitrotyrosyl hybrid was separated from the other members of the hybrid set by DEAE-Sephadex chromatography and then converted to a succinyl-aminotyrosyl hybrid by reduction of the modified tyrosine residues with sodium dithionite. A comparison of the activities of these two hybrids with the activities of the succinyl, nitrotyrosyl and aminotyrosyl derivatives has shown that either the subunits of alkaline phosphatase function independently or if the subunits turnover alternately in a reciprocating mechanism, then the intrinsic activity of each subunit must be strongly dependent on its partner subunit.", "contents": "Hybrids of chemical derivatives of Escherichia coli alkaline phosphatase. The activities of hybrid dimers of alkaline phosphatase containing two chemically modified subunits have been investigated. One hybrid species was prepared by dissociation and reconstitution of a mixture of two variants produced by chemical modification of the native enzyme with succinic anhydride and tetranitromethane, respectively. The succinyl-nitrotyrosyl hybrid was separated from the other members of the hybrid set by DEAE-Sephadex chromatography and then converted to a succinyl-aminotyrosyl hybrid by reduction of the modified tyrosine residues with sodium dithionite. A comparison of the activities of these two hybrids with the activities of the succinyl, nitrotyrosyl and aminotyrosyl derivatives has shown that either the subunits of alkaline phosphatase function independently or if the subunits turnover alternately in a reciprocating mechanism, then the intrinsic activity of each subunit must be strongly dependent on its partner subunit."}
{"id": "PMID:87", "title": "Some physicochemical properties of hemoglobin-manitoba (alpha2 102Ser replaced by Arg (G9) beta2).", "content": "Hb-Manitoba was discovered in 1970 [1] in a Canadian family of British origin. Recently we observed the same variant in a second family, and found that the oxy-derivative of Hb-Manitoba is slightly unstable at 65 degrees C, dissociates less readily at alkaline pH than does Hb-A, and forms asymmetric hybrids with other hemoglobins which are readily detectable by electrophoresis.", "contents": "Some physicochemical properties of hemoglobin-manitoba (alpha2 102Ser replaced by Arg (G9) beta2). Hb-Manitoba was discovered in 1970 [1] in a Canadian family of British origin. Recently we observed the same variant in a second family, and found that the oxy-derivative of Hb-Manitoba is slightly unstable at 65 degrees C, dissociates less readily at alkaline pH than does Hb-A, and forms asymmetric hybrids with other hemoglobins which are readily detectable by electrophoresis."}
{"id": "PMID:88", "title": "The oxygen affinity of haemoglobin Tak, a variant with an elongated beta chain.", "content": "The oxygen affinity was investigated of purified Hb Tak, a human haemoglobin variant with elongated beta-chains. A very low P50 value was found which was not influenced by the addition of 2,3 diphosphoglycerate. The n value was 1, indicating non-cooperativity. The oxygen equilibrium curve of the whole blood haemolysate containing Hbs A and Tak was close to that of Hb A at the top of the curve, while the bottom of the curve greatly deviated from the latter, indicative of small if any interaction between Hb A and Tak during oxygenation.", "contents": "The oxygen affinity of haemoglobin Tak, a variant with an elongated beta chain. The oxygen affinity was investigated of purified Hb Tak, a human haemoglobin variant with elongated beta-chains. A very low P50 value was found which was not influenced by the addition of 2,3 diphosphoglycerate. The n value was 1, indicating non-cooperativity. The oxygen equilibrium curve of the whole blood haemolysate containing Hbs A and Tak was close to that of Hb A at the top of the curve, while the bottom of the curve greatly deviated from the latter, indicative of small if any interaction between Hb A and Tak during oxygenation."}
{"id": "PMID:89", "title": "Effects of membrane ribonuclease and 3'-nucleotidase on the digestion of polyuridylic acid by rat liver plasma membrane.", "content": "1. Fragments of isolated rat liver plasma membrane possess a ribonuclease activity which at pH 7.8 in the presence of 10 mM EDTA can digest polyuridylic acid (poly(U)) and polycytidylic acid (poly(C)) but not polyadenylic acid (poly(A)) and polyguanylic acid (poly(G)). Under these conditions, the membrane preparation does not degrade native or denatured DNA. 2. The products of the reaction with poly(U) (10 mM EDTA present) can be separated on DEAE-Sephadex into oligonucleotides of increasing chain length. Most of the products are di- to hexa-nucleotides which contain terminal 3'-phosphate groups. 3. When EDTA is not present (pH 7.8 or 8.8) the plasma membrane preparation degrades both poly(A) and poly(U). With poly(A) the product is all nucleoside while with poly(U) as substrate most of the product is nucleoside, but also some oligonucleotides are produced. 4. The ribonuclease releases acid soluble products very slowly from high concentrations of poly(U) (mg/ml). 5. Uridine trinucleotide with and without a terminal 3'-phosphate group is degraded by rat liver plasma membrane. The trinucleotide diphosphate is rapidly hydrolyzed to nucleoside while the trinucleotide itself is slowly digested and yields intermediate products, including nucleoside.", "contents": "Effects of membrane ribonuclease and 3'-nucleotidase on the digestion of polyuridylic acid by rat liver plasma membrane. 1. Fragments of isolated rat liver plasma membrane possess a ribonuclease activity which at pH 7.8 in the presence of 10 mM EDTA can digest polyuridylic acid (poly(U)) and polycytidylic acid (poly(C)) but not polyadenylic acid (poly(A)) and polyguanylic acid (poly(G)). Under these conditions, the membrane preparation does not degrade native or denatured DNA. 2. The products of the reaction with poly(U) (10 mM EDTA present) can be separated on DEAE-Sephadex into oligonucleotides of increasing chain length. Most of the products are di- to hexa-nucleotides which contain terminal 3'-phosphate groups. 3. When EDTA is not present (pH 7.8 or 8.8) the plasma membrane preparation degrades both poly(A) and poly(U). With poly(A) the product is all nucleoside while with poly(U) as substrate most of the product is nucleoside, but also some oligonucleotides are produced. 4. The ribonuclease releases acid soluble products very slowly from high concentrations of poly(U) (mg/ml). 5. Uridine trinucleotide with and without a terminal 3'-phosphate group is degraded by rat liver plasma membrane. The trinucleotide diphosphate is rapidly hydrolyzed to nucleoside while the trinucleotide itself is slowly digested and yields intermediate products, including nucleoside."}
{"id": "PMID:90", "title": "Alterations in phospholipid-dependent (Na+ +K+)-ATPase activity due to lipid fluidity. Effects of cholesterol and Mg2+.", "content": "The (Na+ +K+)-activated, Mg2+-dependent ATPase from rabbit kidney outer medulla was prepared in a partially inactivated, soluble form depleted of endogenous phospholipids, using deoxycholate. This preparation was reactivated 10 to 50-fold by sonicated liposomes of phosphatidylserine, but not by non-sonicated phosphatidylserine liposomes or sonicated phosphatidylcholine liposomes. The reconstituted enzyme resembled native membrane preparations of (Na+ +K+)-ATPase in its pH optimum being around 7.0, showing optimal activity at Mg2+:ATP mol ratios of approximately 1 and a Km value for ATP of 0.4 mM. Arrhenius plots of this reactivated activity at a constant pH of 7.0 and an Mg2+: ATP mol ratio of 1:1 showed a discontinuity (sharp change of slope) at 17 degrees C, with activation energy (Ea) values of 13-15 kcal/mol above this temperature and 30-35 kcal below it. A further discontinuity was also found at 8.0 degrees C and the Ea below this was very high (greater than 100 kcal/mol). Increased Mg2+ concentrations at Mg2+:ATP ratios in excess of 1:1 inhibited the (Na+ +K+)-ATPase activity and also abolished the discontinuities in the Arrhenius plots. The addition of cholesterol to phosphatidylserine at a 1:1 mol ratio partially inhibited (Na+ +K+)-ATPase reactivation. Arrhenius plots under these conditions showed a single discontinuity at 20 degrees C and Ea values of 22 and 68 kcal/mol above and below this temperature respectively. The ouabain-insensitive Mg2+-ATPase normally showed a linear Arrhenius plot with an Ea of 8 kcal/mol. The cholesterol-phosphatidylserine mixed liposomes stimulated the Mg2+-ATPase activity, which now also showed a discontinuity at 20 degrees C with, however, an increased value of 14 kcal/mol above this temperature and 6 kcal/mol below. Kinetic studies showed that cholesterol had no significant effect on the Km values for ATP. Since both cholesterol and Mg2+ are known to alter the effects of temperature on the fluidity of phospholipids, the above results are discussed in this context.", "contents": "Alterations in phospholipid-dependent (Na+ +K+)-ATPase activity due to lipid fluidity. Effects of cholesterol and Mg2+. The (Na+ +K+)-activated, Mg2+-dependent ATPase from rabbit kidney outer medulla was prepared in a partially inactivated, soluble form depleted of endogenous phospholipids, using deoxycholate. This preparation was reactivated 10 to 50-fold by sonicated liposomes of phosphatidylserine, but not by non-sonicated phosphatidylserine liposomes or sonicated phosphatidylcholine liposomes. The reconstituted enzyme resembled native membrane preparations of (Na+ +K+)-ATPase in its pH optimum being around 7.0, showing optimal activity at Mg2+:ATP mol ratios of approximately 1 and a Km value for ATP of 0.4 mM. Arrhenius plots of this reactivated activity at a constant pH of 7.0 and an Mg2+: ATP mol ratio of 1:1 showed a discontinuity (sharp change of slope) at 17 degrees C, with activation energy (Ea) values of 13-15 kcal/mol above this temperature and 30-35 kcal below it. A further discontinuity was also found at 8.0 degrees C and the Ea below this was very high (greater than 100 kcal/mol). Increased Mg2+ concentrations at Mg2+:ATP ratios in excess of 1:1 inhibited the (Na+ +K+)-ATPase activity and also abolished the discontinuities in the Arrhenius plots. The addition of cholesterol to phosphatidylserine at a 1:1 mol ratio partially inhibited (Na+ +K+)-ATPase reactivation. Arrhenius plots under these conditions showed a single discontinuity at 20 degrees C and Ea values of 22 and 68 kcal/mol above and below this temperature respectively. The ouabain-insensitive Mg2+-ATPase normally showed a linear Arrhenius plot with an Ea of 8 kcal/mol. The cholesterol-phosphatidylserine mixed liposomes stimulated the Mg2+-ATPase activity, which now also showed a discontinuity at 20 degrees C with, however, an increased value of 14 kcal/mol above this temperature and 6 kcal/mol below. Kinetic studies showed that cholesterol had no significant effect on the Km values for ATP. Since both cholesterol and Mg2+ are known to alter the effects of temperature on the fluidity of phospholipids, the above results are discussed in this context."}
{"id": "PMID:91", "title": "Conformational and molecular responses to pH variation of the purified membrane adenosine triphosphatase of Micrococcus lysodeikticus.", "content": "A preparation of ATPase from the membranes of Micrococcus lysodeikticus, solubilized and more than 95% pure, showed two main bands in analytical polyacrylamide gel electrophoresis. They did not correspond to isoenzymes because one band could be converted into the other by exposure to a mildly alkaline pH value. The conversion was paralleled by changes in molecular weight, circular dichroism and catalytic properties. Denaturation by pH at 25 degrees C was followed by means of circular dichroism, ultracentrifugation and polyacrylamide gel electrophoresis. A large conformational transition took place in the acid range with midpoints at about pH = 3.6 (I = 10(-4) M), 4.3 (I = 0.03 M) and 5.3 (I = 0.1 M). The transition was irreversible. Strong aggregation of the protein occurred in this range of pH. The final product was largely random coil, but even at pH 1.5 dissociation into individual subunits was not complete. However, partial dissociation took place at pH 5 (I = 0.028 M). At this pH value the enzyme was inactive, but 20-30% of the activity could be recovered when the pH was returned to 7.5. In the alkaline region the midpoint of the transition occurred near pH = 11 (I = 0.028 M). The pK of most of the tyrosine residues of the protein was about 10.9. The unfolding was irreversible and the protein was soon converted into peptide species with molecular weights lower than those determined for the subunits by gel electrophoresis in the presence of sodium dodecyl sulphate. Conventional proteolysis did not account for the transformation.", "contents": "Conformational and molecular responses to pH variation of the purified membrane adenosine triphosphatase of Micrococcus lysodeikticus. A preparation of ATPase from the membranes of Micrococcus lysodeikticus, solubilized and more than 95% pure, showed two main bands in analytical polyacrylamide gel electrophoresis. They did not correspond to isoenzymes because one band could be converted into the other by exposure to a mildly alkaline pH value. The conversion was paralleled by changes in molecular weight, circular dichroism and catalytic properties. Denaturation by pH at 25 degrees C was followed by means of circular dichroism, ultracentrifugation and polyacrylamide gel electrophoresis. A large conformational transition took place in the acid range with midpoints at about pH = 3.6 (I = 10(-4) M), 4.3 (I = 0.03 M) and 5.3 (I = 0.1 M). The transition was irreversible. Strong aggregation of the protein occurred in this range of pH. The final product was largely random coil, but even at pH 1.5 dissociation into individual subunits was not complete. However, partial dissociation took place at pH 5 (I = 0.028 M). At this pH value the enzyme was inactive, but 20-30% of the activity could be recovered when the pH was returned to 7.5. In the alkaline region the midpoint of the transition occurred near pH = 11 (I = 0.028 M). The pK of most of the tyrosine residues of the protein was about 10.9. The unfolding was irreversible and the protein was soon converted into peptide species with molecular weights lower than those determined for the subunits by gel electrophoresis in the presence of sodium dodecyl sulphate. Conventional proteolysis did not account for the transformation."}
{"id": "PMID:92", "title": "Membrane-bound enzymes. III. Protease activity in leucocytes in relation to erythrocyte membranes.", "content": "Protease activity was detected in membranes of human bovine erythrocytes prepared by the conventional procedures which include washing and removal of the  \"buffy layer\". The enzyme was extracted by 0.75 M KCNS or (NH4)2SO4 and was activated by 0.4 to 0.5 M of the same salts. Colored, particulate hide powder-azure, membrane fractions and soluble proteins such as hemoglobin, casein or albumin were susceptible to hydrolysis by the membraneous protease. Partial purification of the enzyme was accomplished through disc-gel electrophoresis on polyacrylamide in the presence of 0.25% positively charged detergents like cetyltrimethylammonium bromide. An alkaline protease (pH 7.4) with properties similar to those of the erythrocyte enzyme was found in leucocytes. The similarity between the properties of the leucocytic and erythrocytic proteases and the correlation of the activity in erythrocyte membranes with content of white cells in these preparations, suggest that enzymatic activities in the contaminating leucocytes are responsible for the activity of membraneous proteases in erythrocytes.", "contents": "Membrane-bound enzymes. III. Protease activity in leucocytes in relation to erythrocyte membranes. Protease activity was detected in membranes of human bovine erythrocytes prepared by the conventional procedures which include washing and removal of the  \"buffy layer\". The enzyme was extracted by 0.75 M KCNS or (NH4)2SO4 and was activated by 0.4 to 0.5 M of the same salts. Colored, particulate hide powder-azure, membrane fractions and soluble proteins such as hemoglobin, casein or albumin were susceptible to hydrolysis by the membraneous protease. Partial purification of the enzyme was accomplished through disc-gel electrophoresis on polyacrylamide in the presence of 0.25% positively charged detergents like cetyltrimethylammonium bromide. An alkaline protease (pH 7.4) with properties similar to those of the erythrocyte enzyme was found in leucocytes. The similarity between the properties of the leucocytic and erythrocytic proteases and the correlation of the activity in erythrocyte membranes with content of white cells in these preparations, suggest that enzymatic activities in the contaminating leucocytes are responsible for the activity of membraneous proteases in erythrocytes."}
{"id": "PMID:96", "title": "Polymer concentration dependence of the helix to random coil transition of a charged polypeptide in aqueous salt solution.", "content": "The helix to coil transition of poly(L-glutamic acid) was investigated in 0.05 and 0.005 M aqueous potassium chloride solutions by use of potentiometric titration and circular dichroism measurement. Polymer concentration dependence of the transition was observed in the range from 0.006 to 0.04 monomol/e in 0.005 M KG1 solution. The polymer concentration dependence can be interpreted by current theories of the transition of charged polypeptides and of titration curves of linear weak polyelectrolytes taking the effect of polymer concentration into consideration.", "contents": "Polymer concentration dependence of the helix to random coil transition of a charged polypeptide in aqueous salt solution. The helix to coil transition of poly(L-glutamic acid) was investigated in 0.05 and 0.005 M aqueous potassium chloride solutions by use of potentiometric titration and circular dichroism measurement. Polymer concentration dependence of the transition was observed in the range from 0.006 to 0.04 monomol/e in 0.005 M KG1 solution. The polymer concentration dependence can be interpreted by current theories of the transition of charged polypeptides and of titration curves of linear weak polyelectrolytes taking the effect of polymer concentration into consideration."}
{"id": "PMID:93", "title": "[Structure formation in interphase adsorption layers of lysozyme at liquid boundaries].", "content": "In connection with the modelling of biomembranes regularities of the formation and development of interphase adsorption layers of lysozyme at liquid borders under different conditions and depending on the nature of carbohydrate phase were investigated by the determination of mechanical characteristics of such layers. The investigations carried out showed that the most solid layers appeared under the conditions which assured the formation of the maximum number of intermolecular bonds (which in a common case is performed with maximum disorderlinesss of the macromolecules which get at the interphase).", "contents": "[Structure formation in interphase adsorption layers of lysozyme at liquid boundaries]. In connection with the modelling of biomembranes regularities of the formation and development of interphase adsorption layers of lysozyme at liquid borders under different conditions and depending on the nature of carbohydrate phase were investigated by the determination of mechanical characteristics of such layers. The investigations carried out showed that the most solid layers appeared under the conditions which assured the formation of the maximum number of intermolecular bonds (which in a common case is performed with maximum disorderlinesss of the macromolecules which get at the interphase)."}
{"id": "PMID:94", "title": "[Relation between fluorescence and circular dichroism of the complex of the fluorescence probe 4-dimethylaminochalcone with serum albumin].", "content": "The fluorescence probe(4-dimethylaminochalcone; DMH) was noncovalently linked to human serum albumin (HSA). The variation of pH was due to serum albumin structural changes, which was determined in terms of DMH and HSA fluorescence and CD spectra. Considerable changes of fluorescence and CD spectra were observed at pH 8 and 10, where there is ionization of two more recently titrated tyrosin residues. It is assumed that these two tyrosine residues are in binding region and quench the fluorescence of DMH between pH 4 to 8. Quenching disappears if these residues are ionized (pH greater than 8) or if the protein undergoes the N -F transition (pH less than 4).", "contents": "[Relation between fluorescence and circular dichroism of the complex of the fluorescence probe 4-dimethylaminochalcone with serum albumin]. The fluorescence probe(4-dimethylaminochalcone; DMH) was noncovalently linked to human serum albumin (HSA). The variation of pH was due to serum albumin structural changes, which was determined in terms of DMH and HSA fluorescence and CD spectra. Considerable changes of fluorescence and CD spectra were observed at pH 8 and 10, where there is ionization of two more recently titrated tyrosin residues. It is assumed that these two tyrosine residues are in binding region and quench the fluorescence of DMH between pH 4 to 8. Quenching disappears if these residues are ionized (pH greater than 8) or if the protein undergoes the N -F transition (pH less than 4)."}
{"id": "PMID:95", "title": "[Luminescence study of the effect of temperature on the conformational state of fibrinogen].", "content": "Results are presented of measuring fibrinogen fluorescence parameters in temperature range of 20-80 degrees C at different pH of the solution. It was found that the temperature increase from 20 to 40 degrees C for solutions with pH of 4,5-9,3 were not accompanied by the conformational changes of fibrinogen macromolecules. In the temperature range of 40-50 degrees C for neutral solutions conformational reconstruction of fibrinogen of undenatured character took place. Temperature increase above 50-55 degrees C brings about significant structural changes of fibrinogen molecule which are of denaturation nature.", "contents": "[Luminescence study of the effect of temperature on the conformational state of fibrinogen]. Results are presented of measuring fibrinogen fluorescence parameters in temperature range of 20-80 degrees C at different pH of the solution. It was found that the temperature increase from 20 to 40 degrees C for solutions with pH of 4,5-9,3 were not accompanied by the conformational changes of fibrinogen macromolecules. In the temperature range of 40-50 degrees C for neutral solutions conformational reconstruction of fibrinogen of undenatured character took place. Temperature increase above 50-55 degrees C brings about significant structural changes of fibrinogen molecule which are of denaturation nature."}
{"id": "PMID:103", "title": "[Combined effects of hypoxia and hypercapnia on the functional state of the respiratory center].", "content": "Experiments were conducted on cats under nembutal anesthesia; a study was made of pulse activity of bulbar respiratory neurons, electrical activity of the diaphragm and of the intercostal muscles; pO2, pCO2, pH, arterial blood oxygen saturation were determined in combined action of hypoxia and hypercapnia. When hypoxic gaseous mixture was given for respiration the developing hypocapnia disturbed the discharge rhythmic activity of the respiratory neurons, the respiration acquiring a pathological character of the Cheyne--Stokes type. After addition to the hypoxic gaseous mixture of 2% CO2 the gaseous composition of the arterial blood approached the initial values; this addition prevented the development of hypercapnia and disturbances of rhythmic discharge activity of the respiratory neurons. Addition of 5% CO2 to the hypoxic gaseous mixture produced a negative effect: at first it intensified and then depressed the pulse activity of the respiratory neurons, caused metabolic and respiratory acidosis, and promoted asphyxia.", "contents": "[Combined effects of hypoxia and hypercapnia on the functional state of the respiratory center]. Experiments were conducted on cats under nembutal anesthesia; a study was made of pulse activity of bulbar respiratory neurons, electrical activity of the diaphragm and of the intercostal muscles; pO2, pCO2, pH, arterial blood oxygen saturation were determined in combined action of hypoxia and hypercapnia. When hypoxic gaseous mixture was given for respiration the developing hypocapnia disturbed the discharge rhythmic activity of the respiratory neurons, the respiration acquiring a pathological character of the Cheyne--Stokes type. After addition to the hypoxic gaseous mixture of 2% CO2 the gaseous composition of the arterial blood approached the initial values; this addition prevented the development of hypercapnia and disturbances of rhythmic discharge activity of the respiratory neurons. Addition of 5% CO2 to the hypoxic gaseous mixture produced a negative effect: at first it intensified and then depressed the pulse activity of the respiratory neurons, caused metabolic and respiratory acidosis, and promoted asphyxia."}
{"id": "PMID:104", "title": "[Level of nicotinamide coenzymes in the liver and myocardium of rats poisoned with dichlorethane].", "content": "Experiments were conducted on male rats. A study was made of the content of nicotinamide coenzymes in the liver and myocardium 24 hours after the administration of 0.5 ml of dichloroethane into the stomach. In parallel with disturbance of the morphological structure of the liver and of the myocardium, increase in the activity of alanine and aspargic aminotranspherases in the blood serum, dichloroethane reduced the content of nicotinamide coenzymes and deranged the ratio of their oxidized and reduced forms in these organs.", "contents": "[Level of nicotinamide coenzymes in the liver and myocardium of rats poisoned with dichlorethane]. Experiments were conducted on male rats. A study was made of the content of nicotinamide coenzymes in the liver and myocardium 24 hours after the administration of 0.5 ml of dichloroethane into the stomach. In parallel with disturbance of the morphological structure of the liver and of the myocardium, increase in the activity of alanine and aspargic aminotranspherases in the blood serum, dichloroethane reduced the content of nicotinamide coenzymes and deranged the ratio of their oxidized and reduced forms in these organs."}
{"id": "PMID:105", "title": "[Effect of carbidine on conditioned defense reflexes].", "content": "Chronic experiments were conducted on rats and rabbits; a study was made of the effect of carbidine on the conditioned defence reflexes in stimulation of the mesencephalic part of the reticular formation. Carbidine prevented the depression of the conditioned defence reflexes caused by stimulation of the mesencephalic portion of the reticular formation. This pointed to its depressive influence on the mentioned structures, and was confirmed by experiments on rabbits in recording changes in biocurrents under conditions of stimulation of the mesencephalic reticular formation.", "contents": "[Effect of carbidine on conditioned defense reflexes]. Chronic experiments were conducted on rats and rabbits; a study was made of the effect of carbidine on the conditioned defence reflexes in stimulation of the mesencephalic part of the reticular formation. Carbidine prevented the depression of the conditioned defence reflexes caused by stimulation of the mesencephalic portion of the reticular formation. This pointed to its depressive influence on the mentioned structures, and was confirmed by experiments on rabbits in recording changes in biocurrents under conditions of stimulation of the mesencephalic reticular formation."}
{"id": "PMID:106", "title": "[Level of nicotinamide coenzymes in the myocardium of rats during the effects of methylxanthines (theophylline, theobromine, caffeine) and catecholamines].", "content": "It was shown in acute experiments on rats that one hour after an intraperitoneal injection of theophylline (50 mg/kg) there was a decrease in the NAD + NADP content by 19.4%, a tendency to a fall of NAD.H2 + NADP.H2 was expressed, and the total nicotinamide coferment level was reduced. A tendency to decrease NAD + NADP and the total pyridine nucleotide level was seen after caffeine administration. The action of catecholamines and methylxanthines was compared. Theobromine produced no significant effect on the indices under study. It was shown that isadrine decreased the NAD + NADP level; adrenaline (25 mkg/kg) increased the content of both the oxidized (by 24%) and of the reduced (by 48%) forms of pyridine nucleotides. An increase of adrenaline dose to 1000 mkg/kg was accompanied by reduction of the oxidized forms (by 22.2%) and of the total nicotinamide coferment level (by 18%).", "contents": "[Level of nicotinamide coenzymes in the myocardium of rats during the effects of methylxanthines (theophylline, theobromine, caffeine) and catecholamines]. It was shown in acute experiments on rats that one hour after an intraperitoneal injection of theophylline (50 mg/kg) there was a decrease in the NAD + NADP content by 19.4%, a tendency to a fall of NAD.H2 + NADP.H2 was expressed, and the total nicotinamide coferment level was reduced. A tendency to decrease NAD + NADP and the total pyridine nucleotide level was seen after caffeine administration. The action of catecholamines and methylxanthines was compared. Theobromine produced no significant effect on the indices under study. It was shown that isadrine decreased the NAD + NADP level; adrenaline (25 mkg/kg) increased the content of both the oxidized (by 24%) and of the reduced (by 48%) forms of pyridine nucleotides. An increase of adrenaline dose to 1000 mkg/kg was accompanied by reduction of the oxidized forms (by 22.2%) and of the total nicotinamide coferment level (by 18%)."}
{"id": "PMID:107", "title": "Potable water quality in rural Georgetown County.", "content": "Drinking water supplies of 161 rural communities, in Georgetown County, South Carolina, were randomly selected for sample collection. The analysis showed that most of the waters were slightly acidic. Low, but acceptable concentrations of chloride, copper, fluoride, sodium, cadmium, nitrate and phosphate were found. A few water samples showed higher then recommended levels of arsenic, mercury, zinc and lead. Although only 2% of the samples exceeded the mandatory limit of 0.05 ppm for arsenic, 72% exceeded the recommended level of 0.01 ppm. The mandatory limit for manganese was exceeded in 37% of the waters while 88% exceeded the limit for iron. The high iron content was generally responsible for the high turbidity found in 45% of the samples. The well depth and the consumer income had some bearing on water quality. Statistical evidence suggested that septic tank seepage was partially responsible for nitrate, phosphate, iron and arsenic contamination of shallow water supplies. Lead concentrations appear to vary according to the plumbing used and the pH of the waters.", "contents": "Potable water quality in rural Georgetown County. Drinking water supplies of 161 rural communities, in Georgetown County, South Carolina, were randomly selected for sample collection. The analysis showed that most of the waters were slightly acidic. Low, but acceptable concentrations of chloride, copper, fluoride, sodium, cadmium, nitrate and phosphate were found. A few water samples showed higher then recommended levels of arsenic, mercury, zinc and lead. Although only 2% of the samples exceeded the mandatory limit of 0.05 ppm for arsenic, 72% exceeded the recommended level of 0.01 ppm. The mandatory limit for manganese was exceeded in 37% of the waters while 88% exceeded the limit for iron. The high iron content was generally responsible for the high turbidity found in 45% of the samples. The well depth and the consumer income had some bearing on water quality. Statistical evidence suggested that septic tank seepage was partially responsible for nitrate, phosphate, iron and arsenic contamination of shallow water supplies. Lead concentrations appear to vary according to the plumbing used and the pH of the waters."}
{"id": "PMID:123", "title": "The importance of an innervated and intact antrum and pylorus in preventing postoperative duodenogastric reflux and gastritis.", "content": "This study has investigated the relationship between duodenogastric reflux, gastritis and certain symptoms 6-12 months after three operations for uncomplicated duodenal ulcer. The operations studied were proximal gastric vagotomy (PGV, 20 cases), truncal vagotomy and pyloroplasty (TV+P, 22 cases) and truncal vagotomy and antrectomy (TV+A, 21 cases). Duodenogastric reflux was assessed both by a radiological technique and by measuring the concentration of bilirubin in the gastric aspirate before and after operation. Incidence and severity of postoperative gastritis were determined by endoscopic biopsy. Symptoms were assessed by symptomatic score and Visick grading. There was a significant correlation between duodenal reflux and histological evidence of both severe superficial gastritis and glandular atrophy (P less than 0-01). There was also a close association between the degree of reflux and the presence of severe heartburn, epigastric pain and bile vomiting after operation. The amount of reflux did not differ before operation. There was significantly less reflux following PGV than after either TV+P (P less than 0-025) or TV+A (P less than 0-001). The results indicate that an operation which preserves an innervated and intact antrum and pylorus will protect against postoperative duodenogastric reflux, gastritis and symptoms.", "contents": "The importance of an innervated and intact antrum and pylorus in preventing postoperative duodenogastric reflux and gastritis. This study has investigated the relationship between duodenogastric reflux, gastritis and certain symptoms 6-12 months after three operations for uncomplicated duodenal ulcer. The operations studied were proximal gastric vagotomy (PGV, 20 cases), truncal vagotomy and pyloroplasty (TV+P, 22 cases) and truncal vagotomy and antrectomy (TV+A, 21 cases). Duodenogastric reflux was assessed both by a radiological technique and by measuring the concentration of bilirubin in the gastric aspirate before and after operation. Incidence and severity of postoperative gastritis were determined by endoscopic biopsy. Symptoms were assessed by symptomatic score and Visick grading. There was a significant correlation between duodenal reflux and histological evidence of both severe superficial gastritis and glandular atrophy (P less than 0-01). There was also a close association between the degree of reflux and the presence of severe heartburn, epigastric pain and bile vomiting after operation. The amount of reflux did not differ before operation. There was significantly less reflux following PGV than after either TV+P (P less than 0-025) or TV+A (P less than 0-001). The results indicate that an operation which preserves an innervated and intact antrum and pylorus will protect against postoperative duodenogastric reflux, gastritis and symptoms."}
{"id": "PMID:124", "title": "Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.", "content": "A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident.", "contents": "Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia. A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident."}
{"id": "PMID:125", "title": "Endoscopic papillotomy and removal of gall stones.", "content": "Endoscopic papillotomy was attempted in 59 patients with extrahepatic obstruction of the biliary duct system and was actually performed in 50 patients. A special high-frequency diathermy knife was introduced via a duodenoscope into the terminal common bile duct and the roof of the papilla was incised. In 33 out of 39 patients with choledocholithiasis the stones passed into the duodenum spontaneously or were removed endoscopically. Papillary stenosis without ductal stones was successfully treated with this method in eight out of 11 patients. One perforation of the duodenocholedochal junction occurred and was repaired surgically. Endoscopic papillotomy and stone extraction is a relatively safe and effective method of treating extrahepatic jaundice.", "contents": "Endoscopic papillotomy and removal of gall stones. Endoscopic papillotomy was attempted in 59 patients with extrahepatic obstruction of the biliary duct system and was actually performed in 50 patients. A special high-frequency diathermy knife was introduced via a duodenoscope into the terminal common bile duct and the roof of the papilla was incised. In 33 out of 39 patients with choledocholithiasis the stones passed into the duodenum spontaneously or were removed endoscopically. Papillary stenosis without ductal stones was successfully treated with this method in eight out of 11 patients. One perforation of the duodenocholedochal junction occurred and was repaired surgically. Endoscopic papillotomy and stone extraction is a relatively safe and effective method of treating extrahepatic jaundice."}
{"id": "PMID:128", "title": "Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord.", "content": "The actions of glycine, GABA, alpha-alanine, beta-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by beta-alanine, alpha-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of post-synaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin seletively diminished the postsymaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, alpha- and beta-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, alpha- and beta-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed.", "contents": "Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord. The actions of glycine, GABA, alpha-alanine, beta-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by beta-alanine, alpha-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of post-synaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin seletively diminished the postsymaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, alpha- and beta-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, alpha- and beta-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed."}
{"id": "PMID:129", "title": "The involvement of lysophosphoglycerides in neurotransmitter release; the composition and turnover of phospholipids of synaptic vesicles of guinea-pig cerebral cortex and Torpedo electric organ and the effect of stimulation.", "content": "(1) Crude synaptosomal fractions (P2) derived from guinea-pig cerebral cortex were incubated in the presence of 50 mM KCl in a Krebs-glucose medium. Torpedo marmorata electric organs were stimulated electrically in vivo at 5 pulses/sec for 30 min by electrodes placed on the electric lobe. Synaptic vesicles were isolated from each source and the phospholipid compositions analysed and compared with vesicles  from unstimulated controls. (2) Lysophosphatidylcholine was the only lysophosphoglyceride demonstrable in the synaptic vesicles from either source and its low levels did not increase as a result of chemical or electircal stimulation. In each case there was a close similarity of the phospholipid distributions in the vesicles taken from control and stimulated samples. (3) Control experiments indicated extensive decreases in the acetylcholine content of the vesicles from the stimulated electric organ and smaller decreases in the acetylcholine content of the synaptic vesicles from stimulated crude synaptosomal fractions. These fractions were found to respire linearly in the presence of 10 mM glucose and the vesicle fractions were shown to have low levels of contaiminating membranes as judged by marker enzyme analyses. (4) Crude synaptosomal fractions from guinea-pig cerebral cortex were incubated in a Krebs-glucose medium with labelled fatty acids and [3H]glucose in the presence or absence of 50 mM KCl. Subsynaptosomal fractionation was carried out and specific radioactivities of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were determined in fractions D (synaptic vesicles), E (microsomes) and H (disrupted synaptosomes). The release of neurotransmitter did not significantly enhance the labelling of phospholipids in any of the fractions studied as compared with phospholipids from unstimulated fractions. This was found after two incubation times and using [14C]oleate, [14C]arachidonate, [3H]palmitate and [3H]glucose.", "contents": "The involvement of lysophosphoglycerides in neurotransmitter release; the composition and turnover of phospholipids of synaptic vesicles of guinea-pig cerebral cortex and Torpedo electric organ and the effect of stimulation. (1) Crude synaptosomal fractions (P2) derived from guinea-pig cerebral cortex were incubated in the presence of 50 mM KCl in a Krebs-glucose medium. Torpedo marmorata electric organs were stimulated electrically in vivo at 5 pulses/sec for 30 min by electrodes placed on the electric lobe. Synaptic vesicles were isolated from each source and the phospholipid compositions analysed and compared with vesicles  from unstimulated controls. (2) Lysophosphatidylcholine was the only lysophosphoglyceride demonstrable in the synaptic vesicles from either source and its low levels did not increase as a result of chemical or electircal stimulation. In each case there was a close similarity of the phospholipid distributions in the vesicles taken from control and stimulated samples. (3) Control experiments indicated extensive decreases in the acetylcholine content of the vesicles from the stimulated electric organ and smaller decreases in the acetylcholine content of the synaptic vesicles from stimulated crude synaptosomal fractions. These fractions were found to respire linearly in the presence of 10 mM glucose and the vesicle fractions were shown to have low levels of contaiminating membranes as judged by marker enzyme analyses. (4) Crude synaptosomal fractions from guinea-pig cerebral cortex were incubated in a Krebs-glucose medium with labelled fatty acids and [3H]glucose in the presence or absence of 50 mM KCl. Subsynaptosomal fractionation was carried out and specific radioactivities of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were determined in fractions D (synaptic vesicles), E (microsomes) and H (disrupted synaptosomes). The release of neurotransmitter did not significantly enhance the labelling of phospholipids in any of the fractions studied as compared with phospholipids from unstimulated fractions. This was found after two incubation times and using [14C]oleate, [14C]arachidonate, [3H]palmitate and [3H]glucose."}
{"id": "PMID:132", "title": "Cardiac output response to altered acid-base status during diethyl ether anaesthesia.", "content": "The effects of acid-base changes on cardiac output during diethyl ether anaesthesia were studied in 25 mongrel dogs prepared by surgically implanting a plastic encased non-ferrous core electromagnetic probe on the ascending aorta. The findings are: (1) Metabolic acidaemia produced only slight decrease in cardiac output but a more marked fall became evident with decreasing pH(2) Respiratory acidaemia led to a slight rise in cardiac output. (3) Respiratory alkalaemia decreased cardiac output. (4) Metabolic alkalaemia also produced a decline in cardiac output.", "contents": "Cardiac output response to altered acid-base status during diethyl ether anaesthesia. The effects of acid-base changes on cardiac output during diethyl ether anaesthesia were studied in 25 mongrel dogs prepared by surgically implanting a plastic encased non-ferrous core electromagnetic probe on the ascending aorta. The findings are: (1) Metabolic acidaemia produced only slight decrease in cardiac output but a more marked fall became evident with decreasing pH(2) Respiratory acidaemia led to a slight rise in cardiac output. (3) Respiratory alkalaemia decreased cardiac output. (4) Metabolic alkalaemia also produced a decline in cardiac output."}
{"id": "PMID:133", "title": "The prevention of autolysis of stored cornea using steroid as a lysosome membrane stabilizer.", "content": "Many eyes donated for use in corneal grafting are rejected because of signs of autolysis in the donor material. The purpose of this experimental study was to determine whether hydrocortisone acting as a lysosome membrane stabilizer could prevent or retard autolysis of the corneas under storage, and if so, what was the most efficacious concentration. Different groups of rabbit corneas were placed in saline as controls or in varying concentrations of hydrocortisone (10(-10) M to 10(-4) M at pH 7.4) at 37 degrees C and 4 degrees C. Acid phosphatase released after six hours was measured biochemically. This enzyme was used as a marker enzyme reflecting lysosomal labilization. Results showed a significant stabilization of the lysosomal membrane at 4 degrees C as compared to 37 degrees C. A trend towards stabilization of the lysosomal membrane was seen when 10(-8) M concentration of hydrocortisone at 37 degrees C was used, there being no demonstrable stabilization at 4 degrees C.", "contents": "The prevention of autolysis of stored cornea using steroid as a lysosome membrane stabilizer. Many eyes donated for use in corneal grafting are rejected because of signs of autolysis in the donor material. The purpose of this experimental study was to determine whether hydrocortisone acting as a lysosome membrane stabilizer could prevent or retard autolysis of the corneas under storage, and if so, what was the most efficacious concentration. Different groups of rabbit corneas were placed in saline as controls or in varying concentrations of hydrocortisone (10(-10) M to 10(-4) M at pH 7.4) at 37 degrees C and 4 degrees C. Acid phosphatase released after six hours was measured biochemically. This enzyme was used as a marker enzyme reflecting lysosomal labilization. Results showed a significant stabilization of the lysosomal membrane at 4 degrees C as compared to 37 degrees C. A trend towards stabilization of the lysosomal membrane was seen when 10(-8) M concentration of hydrocortisone at 37 degrees C was used, there being no demonstrable stabilization at 4 degrees C."}
{"id": "PMID:134", "title": "Respiratory effects of H+ and dinitrophenol injections into the brain stem subarachnoid space of fetal lambs.", "content": "Mock cerebrospinal fluid (pH 5.37-8.38) or 2,4-dinitrophenol (DNP) (0.15-1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH.", "contents": "Respiratory effects of H+ and dinitrophenol injections into the brain stem subarachnoid space of fetal lambs. Mock cerebrospinal fluid (pH 5.37-8.38) or 2,4-dinitrophenol (DNP) (0.15-1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH."}
{"id": "PMID:135", "title": "Soil fungistasis: elevation of the exogenous carbon and nitrogen requirements for spore germination by fungistatic volatiles in soils.", "content": "Axenic, washed conidia of Fusarium solani f. sp. phaseoli, Aspergillus flavus, and Verticillium albo-atrum were placed on washed Difco purified agar discs along with an inorganic salt solution containing various levels of carbon and nitrogen substrates. These discs were exposed to volatiles from six soils (pH 5.1-8.6). Fusarium solani macroconidial germination was inhibited mostly by volatiles from soils of pH 5.1, 6.1, 7.0, and 7.5, but high levels of glucose and NH4Cl reversed this inhibition, raising germination to that of no-soil, no-carbon or nitrogen controls. Conidial germination of A. flavus was inhibited mainly by volatiles from high pH (7.0, 7.8, and 8.6) soils, and increased levels of glucose plus an amino acid mixture nullified this inhibition. Volatiles from soils of pH 5.1, 6.1, and 7.5 stimulated A. flavus conidial germination. Assays after the removal of CO2 from the air above soil of pH 5.1 demonstrated that volatiles inhibitory to A. flavus were produced by this soil. Assays indicated that a KOH-soluble compound was a fungistatic soil volatile to F. solani macroconidial germination. The nullification by carbon and nitrogen substrates of F. solani and A. flavus inhibition caused by soil volatiles parallels that for soil fungistasis. Conidial germination of V. albo-atrum was markedly stimulated by volatiles in all soils tested, and was not affected by removal of CO2. Inhibitory soil volatiles may increase the nutritional requirements for spore germination of certain fungi.", "contents": "Soil fungistasis: elevation of the exogenous carbon and nitrogen requirements for spore germination by fungistatic volatiles in soils. Axenic, washed conidia of Fusarium solani f. sp. phaseoli, Aspergillus flavus, and Verticillium albo-atrum were placed on washed Difco purified agar discs along with an inorganic salt solution containing various levels of carbon and nitrogen substrates. These discs were exposed to volatiles from six soils (pH 5.1-8.6). Fusarium solani macroconidial germination was inhibited mostly by volatiles from soils of pH 5.1, 6.1, 7.0, and 7.5, but high levels of glucose and NH4Cl reversed this inhibition, raising germination to that of no-soil, no-carbon or nitrogen controls. Conidial germination of A. flavus was inhibited mainly by volatiles from high pH (7.0, 7.8, and 8.6) soils, and increased levels of glucose plus an amino acid mixture nullified this inhibition. Volatiles from soils of pH 5.1, 6.1, and 7.5 stimulated A. flavus conidial germination. Assays after the removal of CO2 from the air above soil of pH 5.1 demonstrated that volatiles inhibitory to A. flavus were produced by this soil. Assays indicated that a KOH-soluble compound was a fungistatic soil volatile to F. solani macroconidial germination. The nullification by carbon and nitrogen substrates of F. solani and A. flavus inhibition caused by soil volatiles parallels that for soil fungistasis. Conidial germination of V. albo-atrum was markedly stimulated by volatiles in all soils tested, and was not affected by removal of CO2. Inhibitory soil volatiles may increase the nutritional requirements for spore germination of certain fungi."}
{"id": "PMID:136", "title": "Nitrofurazone-reducing enzymes in E. coli and their role in drug activation in vivo.", "content": "Earlier work showed that Escherichia coli contains at least two enzymes which reduce nitrofurazone and other nitrofuran derivatives. One of these enzymes is lacking in some nitrofurazone-resistant mutant strains. We now report that there are three separable nitrofuran reductases in this organism: reductase I (mol. wt. approximately 50 000, insensitive to O2), reductase IIa (mol. wt. approximately 120 000, inhibited by oxygen), reductase IIb (mol. wt. approximately 700 000, inhibited by O2). Unstable metabolites formed during the reduction of nitrofurazone by preparations containing reductases IIa and IIb produce breaks in DNA in vitro. In vivo experiments with nitrofurazone-resistant strains, which lack reductase II but contain reductases IIa and IIb, demonstrated that lethality, mutation, and DNA breakage are all greatly increased when cultures are incubated under anaerobic conditions, i.e., conditions such that reductase II is active. These results provide further evidence for the importance of reductive activation of nitrofurazone.", "contents": "Nitrofurazone-reducing enzymes in E. coli and their role in drug activation in vivo. Earlier work showed that Escherichia coli contains at least two enzymes which reduce nitrofurazone and other nitrofuran derivatives. One of these enzymes is lacking in some nitrofurazone-resistant mutant strains. We now report that there are three separable nitrofuran reductases in this organism: reductase I (mol. wt. approximately 50 000, insensitive to O2), reductase IIa (mol. wt. approximately 120 000, inhibited by oxygen), reductase IIb (mol. wt. approximately 700 000, inhibited by O2). Unstable metabolites formed during the reduction of nitrofurazone by preparations containing reductases IIa and IIb produce breaks in DNA in vitro. In vivo experiments with nitrofurazone-resistant strains, which lack reductase II but contain reductases IIa and IIb, demonstrated that lethality, mutation, and DNA breakage are all greatly increased when cultures are incubated under anaerobic conditions, i.e., conditions such that reductase II is active. These results provide further evidence for the importance of reductive activation of nitrofurazone."}
{"id": "PMID:137", "title": "Enzymatic hydrolysis of agar: purification and characterization of neoagarobiose hydrolase and p-nitrophenyl alpha-galactoside hydrolase.", "content": "The mixture of polysaccharides in the gelling component of agar (agarose) is hydrolyzed to D-galactose and 3,6-anhydro-L-galactose by a series of hydrolytic enzymes obtained from Pseudomonas atlantica. The final degradative step in the pathway of agarose decomposition is the hydrolysis of the alpha-linkage in the dissaccharide neoagarobiose yielding D-galactose and 3,6-anhydro-L-galactose. Pseudomonas atlantica when grown on agar produces two specific enzymes, p-nitrophenyl alpha-galactose hydrolase and neoagarobiose hydrolase. The purification and partial characterization of both enzymes are presented.", "contents": "Enzymatic hydrolysis of agar: purification and characterization of neoagarobiose hydrolase and p-nitrophenyl alpha-galactoside hydrolase. The mixture of polysaccharides in the gelling component of agar (agarose) is hydrolyzed to D-galactose and 3,6-anhydro-L-galactose by a series of hydrolytic enzymes obtained from Pseudomonas atlantica. The final degradative step in the pathway of agarose decomposition is the hydrolysis of the alpha-linkage in the dissaccharide neoagarobiose yielding D-galactose and 3,6-anhydro-L-galactose. Pseudomonas atlantica when grown on agar produces two specific enzymes, p-nitrophenyl alpha-galactose hydrolase and neoagarobiose hydrolase. The purification and partial characterization of both enzymes are presented."}
{"id": "PMID:138", "title": "Temperature and pH optima for 21 species of thermophilic and thermotolerant fungi.", "content": "A glucose-containing mineral medium supplemented with 0.01% yeast extract is described upon which all the species of thermophilic and thermotolerant fungi tested will grow. Thirteen of the 21 species do not require the yeast extract supplement for growth. Using this solid, supplemented mineral medium, the pH and temperature optima for growth of all strains were measured. No correlation was found between temperature optimum and pH optimum among members of the group tested.", "contents": "Temperature and pH optima for 21 species of thermophilic and thermotolerant fungi. A glucose-containing mineral medium supplemented with 0.01% yeast extract is described upon which all the species of thermophilic and thermotolerant fungi tested will grow. Thirteen of the 21 species do not require the yeast extract supplement for growth. Using this solid, supplemented mineral medium, the pH and temperature optima for growth of all strains were measured. No correlation was found between temperature optimum and pH optimum among members of the group tested."}
{"id": "PMID:139", "title": "Physiological differences among isolates of Phytophthora cinnamomi.", "content": "Significant differences in amylase, beta-glucosidase, and phosphatase activities were observed among four Phytophthora cinnamomi isolates grown in nutrient-amended sterilized soil for 20 days. Amylase pH optima for the four isolates were within a relatively narrow range; at pH 5.5 each isolate was within 90% of its peak activity. Isolates SB-216-1, 1-281, and C-39 each exhibited maximal beta-glucosidase activity at pH 5.0 and maximal phosphatase activity at pH 5.0-5.5. Maximal activity for these two enzymes of isolate A-7725 occurred at pH 3.5. In timed experiments, isolates 1-281 and A-7725 exhibited greater amylase activities than did the other two isolates. For beta-glucosidase, greatest activity was observed for SB-216-1; ACTivity of 1-281 was intermediate and least activity was observed for isolates A-7725 and C-39. Isolates SB-216-1 and 1-281 exhibited greatest phosphatase activities; isolate C-39 was intermediate in activity, and A-7725 was least active. Results indicate that significant differences exist among the isolates tested and that these differences can be quantitatively measured by the methods described.", "contents": "Physiological differences among isolates of Phytophthora cinnamomi. Significant differences in amylase, beta-glucosidase, and phosphatase activities were observed among four Phytophthora cinnamomi isolates grown in nutrient-amended sterilized soil for 20 days. Amylase pH optima for the four isolates were within a relatively narrow range; at pH 5.5 each isolate was within 90% of its peak activity. Isolates SB-216-1, 1-281, and C-39 each exhibited maximal beta-glucosidase activity at pH 5.0 and maximal phosphatase activity at pH 5.0-5.5. Maximal activity for these two enzymes of isolate A-7725 occurred at pH 3.5. In timed experiments, isolates 1-281 and A-7725 exhibited greater amylase activities than did the other two isolates. For beta-glucosidase, greatest activity was observed for SB-216-1; ACTivity of 1-281 was intermediate and least activity was observed for isolates A-7725 and C-39. Isolates SB-216-1 and 1-281 exhibited greatest phosphatase activities; isolate C-39 was intermediate in activity, and A-7725 was least active. Results indicate that significant differences exist among the isolates tested and that these differences can be quantitatively measured by the methods described."}
{"id": "PMID:140", "title": "Regulation and properties of an invertase from Clostridium pasteurianum.", "content": "An intracellular invertase was induced in cultures of Clostridium pasteurianum utilizing sucrose as its carbon source for growth. This enzyme synthesis could be repressed by the addition of fructose of a sucrose-growing culture. In contrast, invertase activity was not affected by the addition of glucose to sucrose-growing cells and this enzyme could be induced in a glucose-metabolizing culture by the addition of sucrose. This enzyme was purified 10.5-fold over the induced lese, EC 3.2.1.26) by substrate-specificity studies. Invertase had a pH optimum of 6.5 and an apparent Km of 79.5 mM for sucrose, and required high concentration of potassium phosphate for maximum activity. Invertase was completely inactivated by a 2-min heat treatment at 60 degrees C. This enzyme was strongly inhibited by p-hydroxymercuribenzoate (pCMB) and weakly inhibited by 5,5'-dithiobis(2-nitrobenzoic acid), while cysteine could substantially reverse pCMB) inhibition, suggesting that sulfhydryl group(s) were necessary for invertase activity.", "contents": "Regulation and properties of an invertase from Clostridium pasteurianum. An intracellular invertase was induced in cultures of Clostridium pasteurianum utilizing sucrose as its carbon source for growth. This enzyme synthesis could be repressed by the addition of fructose of a sucrose-growing culture. In contrast, invertase activity was not affected by the addition of glucose to sucrose-growing cells and this enzyme could be induced in a glucose-metabolizing culture by the addition of sucrose. This enzyme was purified 10.5-fold over the induced lese, EC 3.2.1.26) by substrate-specificity studies. Invertase had a pH optimum of 6.5 and an apparent Km of 79.5 mM for sucrose, and required high concentration of potassium phosphate for maximum activity. Invertase was completely inactivated by a 2-min heat treatment at 60 degrees C. This enzyme was strongly inhibited by p-hydroxymercuribenzoate (pCMB) and weakly inhibited by 5,5'-dithiobis(2-nitrobenzoic acid), while cysteine could substantially reverse pCMB) inhibition, suggesting that sulfhydryl group(s) were necessary for invertase activity."}
{"id": "PMID:141", "title": "Characterization studies on the membrane-bound adenosine triphosphatase (ATPase) of Azotobacter vinelandii.", "content": "The adenosinetriphosphatase (ATPase) (EC 3.6.1.3) activity in Azotobacter vinelandii concentrates in the membranous R3 fraction that is directly associated with Azotobacter electron transport function. Sonically disrupted Azotobacter cells were examined for distribution of ATPase activity and the highest specific activity (and activity units) was consistently found in the particulate R3 membranous fraction which sediments on ultracentrifugation at 144 000 X g for 2 h. When the sonication time interval was increased, the membrane-bound ATPase activity could neither be solubilized nor released into the supernatant fraction. Optimal ATPase activty occurred at pH 8.0; Mg2+ ion when added to the assay was stimulatory. Maximal activity always occurred when the Mg2+:ATP stoichiometry was 1:1 on a molar ratio at the 5 mM concentration level. Sodium and potassium ions had no stimulatory effect. The reaction kinetics were linear for the time intervals studied (0-60 min). The membrane-bound ATPase in the R3 fraction was stimulated 12-fold by treatment wiTH TRypsin, and fractionation studies showed that trypsin treatment did not solubilize ATPase activity off the membranous R3 electron transport fraction. The ATPase was not cold labile and the temperature during the preparation of the R3 fraction had no effect on activity; overnight refrigeration at 4 degrees C, however, resulted in a 25% loss of activity as compared with a 14% loss when the R3 fraction was stored overnight at 25 degrees C. A marked inactivation (although variable, usually about 60%) did occur by overnight freezing (-20 degrees C), and subsequent sonication failed to restore ATPase activity. This indicates that membrane reaggregation (by freezing) was not responsible for ATPase inactivation. The addition of azide, ouabain, 2,4-dinitrophenol, or oligomycin to the assay system resulted in neither inhibition nor stimulation of the ATPase activity. The property of trypsin activation and that ATPase activity is highest in the R3 electron transport fraction suggests that its probable functional role is in coupling of electron transport to oxidative phosphorylation.", "contents": "Characterization studies on the membrane-bound adenosine triphosphatase (ATPase) of Azotobacter vinelandii. The adenosinetriphosphatase (ATPase) (EC 3.6.1.3) activity in Azotobacter vinelandii concentrates in the membranous R3 fraction that is directly associated with Azotobacter electron transport function. Sonically disrupted Azotobacter cells were examined for distribution of ATPase activity and the highest specific activity (and activity units) was consistently found in the particulate R3 membranous fraction which sediments on ultracentrifugation at 144 000 X g for 2 h. When the sonication time interval was increased, the membrane-bound ATPase activity could neither be solubilized nor released into the supernatant fraction. Optimal ATPase activty occurred at pH 8.0; Mg2+ ion when added to the assay was stimulatory. Maximal activity always occurred when the Mg2+:ATP stoichiometry was 1:1 on a molar ratio at the 5 mM concentration level. Sodium and potassium ions had no stimulatory effect. The reaction kinetics were linear for the time intervals studied (0-60 min). The membrane-bound ATPase in the R3 fraction was stimulated 12-fold by treatment wiTH TRypsin, and fractionation studies showed that trypsin treatment did not solubilize ATPase activity off the membranous R3 electron transport fraction. The ATPase was not cold labile and the temperature during the preparation of the R3 fraction had no effect on activity; overnight refrigeration at 4 degrees C, however, resulted in a 25% loss of activity as compared with a 14% loss when the R3 fraction was stored overnight at 25 degrees C. A marked inactivation (although variable, usually about 60%) did occur by overnight freezing (-20 degrees C), and subsequent sonication failed to restore ATPase activity. This indicates that membrane reaggregation (by freezing) was not responsible for ATPase inactivation. The addition of azide, ouabain, 2,4-dinitrophenol, or oligomycin to the assay system resulted in neither inhibition nor stimulation of the ATPase activity. The property of trypsin activation and that ATPase activity is highest in the R3 electron transport fraction suggests that its probable functional role is in coupling of electron transport to oxidative phosphorylation."}
{"id": "PMID:142", "title": "Effects of zinc-smelter emissions on forest soil microflora.", "content": "Within 2 km of a zinc (Zn) smelter in Palmerton, Pennsylvania, near the Lehigh Water Gap, up to 13.5% Zn by weight has been measured in the O2 horizon of the soil, and up to 8% Zn in the A1 horizon. The total numbers of bacteria, actinomycetes, and fungi (measured by dilution plate counts) were greatly reduced in the most severely Zn-contaminated soils compared with control soils. The reduction of microbial populations may be a partial cause of the decreased rate of litter decomposition at Lehigh Gap. Growth of most bacteria from control sites was reduced by 100 to 200 muM Zn, most actinomycetes by 100 muM Zn, and most fungi by 100 to 1000 muM Zn in thin-Pablum extract agar (TPab). All the tested actinomycetes and non-spore-forming bacteria isolated from Zn-contaminated Lehigh Gap soils were Zn-tolerant, growing normally in media containing 600-2000 muM Zn. Most fungi, regardless of source, were capable of at least 50% of normal growth at 700 muM Zn. Zinc-tolerant bacteria, actinomycetes, and fungi were readily isolated from low-Zn soils, suggesting that selection for Zn tolerance may proceed rapidly. Acidophilic Mortierella species have been selectively eliminated near the smelter, apparently because of elevated soil pH. Peryronellaea glomerata (Corda) Goidanich and Coniothyrium spp. were found only in the high-Zn soils.", "contents": "Effects of zinc-smelter emissions on forest soil microflora. Within 2 km of a zinc (Zn) smelter in Palmerton, Pennsylvania, near the Lehigh Water Gap, up to 13.5% Zn by weight has been measured in the O2 horizon of the soil, and up to 8% Zn in the A1 horizon. The total numbers of bacteria, actinomycetes, and fungi (measured by dilution plate counts) were greatly reduced in the most severely Zn-contaminated soils compared with control soils. The reduction of microbial populations may be a partial cause of the decreased rate of litter decomposition at Lehigh Gap. Growth of most bacteria from control sites was reduced by 100 to 200 muM Zn, most actinomycetes by 100 muM Zn, and most fungi by 100 to 1000 muM Zn in thin-Pablum extract agar (TPab). All the tested actinomycetes and non-spore-forming bacteria isolated from Zn-contaminated Lehigh Gap soils were Zn-tolerant, growing normally in media containing 600-2000 muM Zn. Most fungi, regardless of source, were capable of at least 50% of normal growth at 700 muM Zn. Zinc-tolerant bacteria, actinomycetes, and fungi were readily isolated from low-Zn soils, suggesting that selection for Zn tolerance may proceed rapidly. Acidophilic Mortierella species have been selectively eliminated near the smelter, apparently because of elevated soil pH. Peryronellaea glomerata (Corda) Goidanich and Coniothyrium spp. were found only in the high-Zn soils."}
{"id": "PMID:143", "title": "alpha-Naphthoflavone activation of 6-hydroxymethylbenzo(alpha)pyrene synthetase.", "content": "alpha-Naphthoflavone activates the aryl hydroxymethyl synthetase of both the microsomal membrane-bound and soluble enzymes of rat liver and rat lung. The enzyme catalyzes the hydroxymethylation of benzo(alpha)pyrene to the 6-hydroxymethyl derivative.", "contents": "alpha-Naphthoflavone activation of 6-hydroxymethylbenzo(alpha)pyrene synthetase. alpha-Naphthoflavone activates the aryl hydroxymethyl synthetase of both the microsomal membrane-bound and soluble enzymes of rat liver and rat lung. The enzyme catalyzes the hydroxymethylation of benzo(alpha)pyrene to the 6-hydroxymethyl derivative."}
{"id": "PMID:148", "title": "The effects of the continuous administration of N,N-dimethyl-4-phenylazoaniline (DAB) on the activities and the inducibilities of some drug-metabolizing enzymes in rat liver.", "content": "(1) The effect of feeding a relatively low-protein diet containing 0.06% DAB for 29 weeks on the activity of DAB-azoreductase, nitroreductase (p-nitrobenzoic acid), N-oxidase (N,N-dimethylaniline), N-demethylase (DAB), cytochrome P-450, NADPH-cytochrome c reductase, beta-glucuronidase and arylsulphatase A were studied. Rapid decreases occurred in the activities of the first six enzymes, reaching minimal values at between 4 and 8 weeks. Activities then increased in all cases to control or nearly control levels. This rate of increase was least for cytochrome P-450. At 4 weeks azoreductase activity with the chemotherapeutic agent CB10-252 (I) as substrate was significantly higher than in control rats. Early increases occurred in the activities of beta-glucuronidase and arylsulphatase A and the activity of the latter never dropped below the control level. (2) An investigation was made of the differential effects of dye feeding on some of the enzyme activities in the two major liver lobes and differences were found. (3) The effect of phenobarbital (PB) pretreatment on the DAB-fed rats was studied at 4-week intervals. The activities of DAB-azoreductase and of nitroreductase increased throughout the whole period, while the activities of the lysosomal enzymes were decreased. (4) After feeding DAB for 4 weeks the effect of PB and 3-methylcholanthrene (MC) on the activities of DAB-azoreductase, CB10-252-azoreductase and components of the azoreductases-cytochrome P-450, NADPH-cytochrome c reductase, the CO-CB10-252-azoreductase was not induced by PB or MC, and CO did not inhibit its reduction. Its reduction depended only slightly on NADH. CO caused a greater relative decrease in the activity of DAB-azoreductase in dye-fed animals and also in animals following PB and MC pretreatment, implying a greater role of  cytochrome P-450 in dye-fed animals.", "contents": "The effects of the continuous administration of N,N-dimethyl-4-phenylazoaniline (DAB) on the activities and the inducibilities of some drug-metabolizing enzymes in rat liver. (1) The effect of feeding a relatively low-protein diet containing 0.06% DAB for 29 weeks on the activity of DAB-azoreductase, nitroreductase (p-nitrobenzoic acid), N-oxidase (N,N-dimethylaniline), N-demethylase (DAB), cytochrome P-450, NADPH-cytochrome c reductase, beta-glucuronidase and arylsulphatase A were studied. Rapid decreases occurred in the activities of the first six enzymes, reaching minimal values at between 4 and 8 weeks. Activities then increased in all cases to control or nearly control levels. This rate of increase was least for cytochrome P-450. At 4 weeks azoreductase activity with the chemotherapeutic agent CB10-252 (I) as substrate was significantly higher than in control rats. Early increases occurred in the activities of beta-glucuronidase and arylsulphatase A and the activity of the latter never dropped below the control level. (2) An investigation was made of the differential effects of dye feeding on some of the enzyme activities in the two major liver lobes and differences were found. (3) The effect of phenobarbital (PB) pretreatment on the DAB-fed rats was studied at 4-week intervals. The activities of DAB-azoreductase and of nitroreductase increased throughout the whole period, while the activities of the lysosomal enzymes were decreased. (4) After feeding DAB for 4 weeks the effect of PB and 3-methylcholanthrene (MC) on the activities of DAB-azoreductase, CB10-252-azoreductase and components of the azoreductases-cytochrome P-450, NADPH-cytochrome c reductase, the CO-CB10-252-azoreductase was not induced by PB or MC, and CO did not inhibit its reduction. Its reduction depended only slightly on NADH. CO caused a greater relative decrease in the activity of DAB-azoreductase in dye-fed animals and also in animals following PB and MC pretreatment, implying a greater role of  cytochrome P-450 in dye-fed animals."}
{"id": "PMID:149", "title": "Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2\"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity.", "content": "The system involved in the reduction of 2-[4'-di(2''-bromopropyl) aminophenylazolbenzoic acid (CB10-252), an agent designed for treating primary liver cell cancer, has been demonstrated to be localised mainly in the 108 000 X g supernatant fraction of rat liver homogenate. It is also present in other organs particularly in the spleen. DAB-azoreductase as shown previously is present almost entirely in the microsomal fraction and is found in high concentration only in liver. The pH maximum for CB10-252-azoreductase implying the importance of the 2'-carboxyl group in determining substrate specificity. The use of enzyme inhibitors and other additives showed that CB10-252 WAS NOT AXANTHINE OXIDASE OR DIHYDROFOLATE REDUCTASE. Its activity was not affected by carbon monoxide, phenobarbitone (PB), or 3-methylcholanthrene (MC) pretreatment. Enhancement of the activity by ferrous ions and FAD indicated that at least part of the reduction system could involve a flavoprotein with FAD as the prosthetic group. The activity of CB10-252-azoreductase and methylred-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems.", "contents": "Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2\"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity. The system involved in the reduction of 2-[4'-di(2''-bromopropyl) aminophenylazolbenzoic acid (CB10-252), an agent designed for treating primary liver cell cancer, has been demonstrated to be localised mainly in the 108 000 X g supernatant fraction of rat liver homogenate. It is also present in other organs particularly in the spleen. DAB-azoreductase as shown previously is present almost entirely in the microsomal fraction and is found in high concentration only in liver. The pH maximum for CB10-252-azoreductase implying the importance of the 2'-carboxyl group in determining substrate specificity. The use of enzyme inhibitors and other additives showed that CB10-252 WAS NOT AXANTHINE OXIDASE OR DIHYDROFOLATE REDUCTASE. Its activity was not affected by carbon monoxide, phenobarbitone (PB), or 3-methylcholanthrene (MC) pretreatment. Enhancement of the activity by ferrous ions and FAD indicated that at least part of the reduction system could involve a flavoprotein with FAD as the prosthetic group. The activity of CB10-252-azoreductase and methylred-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems."}
{"id": "PMID:150", "title": "Mercury inhibition of avian fatty acid synthetase complex.", "content": "(1) Subcutaneous or intra-abdominal injections of 8 mg of HgCl2/100 g body weight markedly depressed hepatic fatty acid synthetase activity of chicks at 1 h post-injection. The depression occurred despite the fact that the chicks continued to eat up until the time they were killed. Under these same conditions, the hepatic activity of acetyl-CoA carboxylase (EC 6.4.1.2) was not affected by HgCl2, while the activity of the mitochondrial system of fatty acid elongation was stimulated. (2) When 2-mercaptoethanol was included in the incubation medium for a highly purified preparation of fatty acid synthetase, 500 muM HgCl2 was required to show definite inhibition of the enzyme. When 2-mercaptoethanol was omitted, 50 muM HgCl2 was inhibitory and 100 muM HgCl2 abolished enzyme activity. (3) 2 mM dithiothreitol completely protected the purified fatty acid synthetase preparation from inhibition by 100 muM HgCl2. When dithiothreitol was added after the addition of enzyme to the mercury-containing medium, protection of the enzyme was not complete. (4) Dialysis of cytosol fractions from chicks injected with HgCl2 against 500 vol. of 0.2 M potassium phosphate buffer (pH 7.0) containing 1 mM EDTA and 10 mM dithiothreitol for 4 h at 4 degrees stimulated the fatty acid synthetase activity of the fractions. Dialysis of cytosol fractions from noninjected chicks under the same conditions was without effect on fatty acid synthetase activity. (5) These data support the hypothesis that the inhibitory effect of HgCl2 administered in vivo on hepatic fatty acid synthetase activity in chicks is mediated through the interaction of mercury with the sulfhydryl groups of the enzyme.", "contents": "Mercury inhibition of avian fatty acid synthetase complex. (1) Subcutaneous or intra-abdominal injections of 8 mg of HgCl2/100 g body weight markedly depressed hepatic fatty acid synthetase activity of chicks at 1 h post-injection. The depression occurred despite the fact that the chicks continued to eat up until the time they were killed. Under these same conditions, the hepatic activity of acetyl-CoA carboxylase (EC 6.4.1.2) was not affected by HgCl2, while the activity of the mitochondrial system of fatty acid elongation was stimulated. (2) When 2-mercaptoethanol was included in the incubation medium for a highly purified preparation of fatty acid synthetase, 500 muM HgCl2 was required to show definite inhibition of the enzyme. When 2-mercaptoethanol was omitted, 50 muM HgCl2 was inhibitory and 100 muM HgCl2 abolished enzyme activity. (3) 2 mM dithiothreitol completely protected the purified fatty acid synthetase preparation from inhibition by 100 muM HgCl2. When dithiothreitol was added after the addition of enzyme to the mercury-containing medium, protection of the enzyme was not complete. (4) Dialysis of cytosol fractions from chicks injected with HgCl2 against 500 vol. of 0.2 M potassium phosphate buffer (pH 7.0) containing 1 mM EDTA and 10 mM dithiothreitol for 4 h at 4 degrees stimulated the fatty acid synthetase activity of the fractions. Dialysis of cytosol fractions from noninjected chicks under the same conditions was without effect on fatty acid synthetase activity. (5) These data support the hypothesis that the inhibitory effect of HgCl2 administered in vivo on hepatic fatty acid synthetase activity in chicks is mediated through the interaction of mercury with the sulfhydryl groups of the enzyme."}
{"id": "PMID:151", "title": "[Basic phospholipase of Naja nigricollis venom].", "content": "It is confirmed that N. nigricollis venom contains several phospholipases one of these is a basic phospholipase A. This enzyme is toxic for mice when injected intravenously. In vitro it reacts on egg yolk lecithin producing lysolecithin and prevents the phenomenon of blood clotting. An immunological identity has been established between this basic phospholipase and two acidic phospholipases present in the same venom.", "contents": "[Basic phospholipase of Naja nigricollis venom]. It is confirmed that N. nigricollis venom contains several phospholipases one of these is a basic phospholipase A. This enzyme is toxic for mice when injected intravenously. In vitro it reacts on egg yolk lecithin producing lysolecithin and prevents the phenomenon of blood clotting. An immunological identity has been established between this basic phospholipase and two acidic phospholipases present in the same venom."}
{"id": "PMID:152", "title": "[Spontaneous mortality and vascular lesions in 3 rat strains with different blood pressure levels].", "content": "We have observed a high and significant mortality in spontaneously hypertensive rats compared to normotensive and hypotensive controls, in the fifth generation. The hypertensive rats exhibited a high frequency of cerebral haemorrhage and periarteritis nodosa.", "contents": "[Spontaneous mortality and vascular lesions in 3 rat strains with different blood pressure levels]. We have observed a high and significant mortality in spontaneously hypertensive rats compared to normotensive and hypotensive controls, in the fifth generation. The hypertensive rats exhibited a high frequency of cerebral haemorrhage and periarteritis nodosa."}
{"id": "PMID:153", "title": "Effects of decreasing arterial blood pressure on cerebral blood flow in the baboon. Influence of the sympathetic nervous system.", "content": "The influence of the sympathetic nervous system on the cerebral circulatory response to graded reductions in mean arterial blood pressure was studied in anesthetized baboons. Cerebral blood flow was measured by the 133Xe clearance method, and arterial blood pressure was decreased by controlled hemorrhage. In normal baboons, the constancy of cerebral blood flow was maintained until mean arterial blood pressure was approximately 65% of the base-line value; thereafter, cerebral blood flow decreased when arterial blood pressure was reduced. Superior cervical sympathectomy of 2-3 weeks duration did not affect the normal response. In contrast, both acute surgical sympathectomy (cervical trunk division) and alpha-receptor blockade (1.5 mg/kg of phenoxybenzamine) enhanced the maintenance of cerebral blood flow in the face of hemorrhagic hypotension in that cerebral blood flow did not decrease until mean arterial blood pressure was approximately 35% of the base-line value. The results indicate that the sympathetic nervous system is not involved in the maintenance of cerebral blood flow in the face of a fall in arterial blood pressure. Indeed, the implication is that the sympathicoadrenal discharge accompanying hemorrhagic hypotension is detrimental to, rather than responsible for,  cerebral autoregulation.", "contents": "Effects of decreasing arterial blood pressure on cerebral blood flow in the baboon. Influence of the sympathetic nervous system. The influence of the sympathetic nervous system on the cerebral circulatory response to graded reductions in mean arterial blood pressure was studied in anesthetized baboons. Cerebral blood flow was measured by the 133Xe clearance method, and arterial blood pressure was decreased by controlled hemorrhage. In normal baboons, the constancy of cerebral blood flow was maintained until mean arterial blood pressure was approximately 65% of the base-line value; thereafter, cerebral blood flow decreased when arterial blood pressure was reduced. Superior cervical sympathectomy of 2-3 weeks duration did not affect the normal response. In contrast, both acute surgical sympathectomy (cervical trunk division) and alpha-receptor blockade (1.5 mg/kg of phenoxybenzamine) enhanced the maintenance of cerebral blood flow in the face of hemorrhagic hypotension in that cerebral blood flow did not decrease until mean arterial blood pressure was approximately 35% of the base-line value. The results indicate that the sympathetic nervous system is not involved in the maintenance of cerebral blood flow in the face of a fall in arterial blood pressure. Indeed, the implication is that the sympathicoadrenal discharge accompanying hemorrhagic hypotension is detrimental to, rather than responsible for,  cerebral autoregulation."}
{"id": "PMID:154", "title": "Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung.", "content": "An isolated perfused canine lung preparation in which determinants of vascular caliber could be individually controlled was developed. The relation of pulmonary arterial (Pa), venous (PV), and alveolar (PA) pressures was such that Pa greater than PA greater than PV throughout the whole lung. The addition of isoprenaline to the perfusate abolished vascular reactivity. Once stability was reached, vascular cross-sectional area remained acceptably constant for 2.25 hours as judged by normalized conductance. The influence of perfusate hematocrit, blood gas tensions, and pH on pressure-flow relations was then studied in 15 isolated canine lungs. The hematocrit-vascular conductance relation was derived at constant perfusion pressure. Conductance varied linearly with hematocrit over a range of 16.5 to 89.5%. Mean pulmonary arterial blood gas tensions were: PO2 = 121 mm Hg, PCO2 = 28 mm Hg, and pH = 7.46. Acute respiratory acidosis (PO2 = 30 mm Hg, PCO2 = 81 mm Hg, pH = 7.17) and lactic acidosis and hypoxemia (PO2 = 32 mm Hg, PCO2 = 21 mm Hg, pH = 6.96) did not significantly alter this relation. Transformation of the conductance-hematocrit data indicated that hematocrit was the most important determinant of relative apparent viscosity of the blood. Both acute respiratory and lactic acidosis failed to significantly increase relative viscosity within the range of hematocrit usually found in secondary polycythemia.", "contents": "Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung. An isolated perfused canine lung preparation in which determinants of vascular caliber could be individually controlled was developed. The relation of pulmonary arterial (Pa), venous (PV), and alveolar (PA) pressures was such that Pa greater than PA greater than PV throughout the whole lung. The addition of isoprenaline to the perfusate abolished vascular reactivity. Once stability was reached, vascular cross-sectional area remained acceptably constant for 2.25 hours as judged by normalized conductance. The influence of perfusate hematocrit, blood gas tensions, and pH on pressure-flow relations was then studied in 15 isolated canine lungs. The hematocrit-vascular conductance relation was derived at constant perfusion pressure. Conductance varied linearly with hematocrit over a range of 16.5 to 89.5%. Mean pulmonary arterial blood gas tensions were: PO2 = 121 mm Hg, PCO2 = 28 mm Hg, and pH = 7.46. Acute respiratory acidosis (PO2 = 30 mm Hg, PCO2 = 81 mm Hg, pH = 7.17) and lactic acidosis and hypoxemia (PO2 = 32 mm Hg, PCO2 = 21 mm Hg, pH = 6.96) did not significantly alter this relation. Transformation of the conductance-hematocrit data indicated that hematocrit was the most important determinant of relative apparent viscosity of the blood. Both acute respiratory and lactic acidosis failed to significantly increase relative viscosity within the range of hematocrit usually found in secondary polycythemia."}
{"id": "PMID:155", "title": "Interaction of the chemoreflex and the pulmonary inflation reflex in the regulation of coronary circulation in conscious dogs.", "content": "The interaction of chemoreflex and pulmonary inflation reflex control of the coronary circulation was examined in conscious dogs by comparing the responses to chemoreflex stimulation (intracarotid injection of nicotine) when ventilation was allowed to increase with those when ventilation was controlled. The responses were also compared with those elicited by both forced mechanical and spontaneous hyperinflation. When the heart rate was constant, intracarotidly administered nicotine induced an increase in the depth of respiration followed closely by an increase in late diastolic coronary flow from 48 +/- 2 to 106 +/- 8 ml/min and a reduction in late diastolic coronary resistance from 1.62 +/- 0.08 to 0.78 +/- 0.06 mm Hg/ml min-1. After beta-receptor and cholinergic blockade, a similar coronary dilation in response to nicotine occurred only when ventilation was allowed to increase. However, when ventilation was controlled, intracarotidly administered nicotine increased coronary resistance after combined beta-receptor and cholinergic blockade. The reflex coronary dilation was not observed after carotid sinus nerve section or after alpha-receptor blockade. Thus, nicotine stimulation of the carotid chemoreflex results in a striking coronary dilation that has two components. The minor component involves a chemoreflex with its efferent pathway in tthe vagi. The major component of coronary dilation follows an increase in the depth of respiration, and its efferent component appears to involve withdrawal of alpha-adrenergic constrictor tone. An almost identical period of reflex coronary dilation followed either forced mechanical or spontaneous hyperinflation in the conscious dog.", "contents": "Interaction of the chemoreflex and the pulmonary inflation reflex in the regulation of coronary circulation in conscious dogs. The interaction of chemoreflex and pulmonary inflation reflex control of the coronary circulation was examined in conscious dogs by comparing the responses to chemoreflex stimulation (intracarotid injection of nicotine) when ventilation was allowed to increase with those when ventilation was controlled. The responses were also compared with those elicited by both forced mechanical and spontaneous hyperinflation. When the heart rate was constant, intracarotidly administered nicotine induced an increase in the depth of respiration followed closely by an increase in late diastolic coronary flow from 48 +/- 2 to 106 +/- 8 ml/min and a reduction in late diastolic coronary resistance from 1.62 +/- 0.08 to 0.78 +/- 0.06 mm Hg/ml min-1. After beta-receptor and cholinergic blockade, a similar coronary dilation in response to nicotine occurred only when ventilation was allowed to increase. However, when ventilation was controlled, intracarotidly administered nicotine increased coronary resistance after combined beta-receptor and cholinergic blockade. The reflex coronary dilation was not observed after carotid sinus nerve section or after alpha-receptor blockade. Thus, nicotine stimulation of the carotid chemoreflex results in a striking coronary dilation that has two components. The minor component involves a chemoreflex with its efferent pathway in tthe vagi. The major component of coronary dilation follows an increase in the depth of respiration, and its efferent component appears to involve withdrawal of alpha-adrenergic constrictor tone. An almost identical period of reflex coronary dilation followed either forced mechanical or spontaneous hyperinflation in the conscious dog."}
{"id": "PMID:156", "title": "Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts.", "content": "The rate of coronary blood flow was varied in isolated working rat heart preparations to determine its influence on the rate of glocose utilization, tissue high-energy phosphates, and intracellular pH. A 60% reduction in coronary blood flow resulted in a 30% reduction in oxygen consumption, an accelerated rate of glusoe utilization, lower tissue levels of high-energy phosphate, and higher tissue levels of lactate and H+. Ventricular performance deteriorated as reflected by a decrease in heart rate and peak systolic pressure. Further reductions in coronary blood flow resulted in inhibition of glycolysis, a greater decrease in tissue levels of high-energy phosphates, and higher tissue levels of both lactate and H+. These changes in glycolytic flux, tissue metabolites, and ventricular performance were proportional to the degree of restriction in coronary blood flow. The importance of coronary blood flow and washout of the interstitial space in the maintenance of accelerated glycolytic flux in oxygen-deficient hearts is emphasized. It is concluded that acceleration of ATP production from glycolysis can occur only in the marginally ischemic tissue in the peripheral area of tissue supplied by an occluded artery. The central area of tissue which receives a low rate of coronary blood flow will have a reduced rate of ATP production due to both a lack of oxygen and an inhibition of glycolysis.", "contents": "Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts. The rate of coronary blood flow was varied in isolated working rat heart preparations to determine its influence on the rate of glocose utilization, tissue high-energy phosphates, and intracellular pH. A 60% reduction in coronary blood flow resulted in a 30% reduction in oxygen consumption, an accelerated rate of glusoe utilization, lower tissue levels of high-energy phosphate, and higher tissue levels of lactate and H+. Ventricular performance deteriorated as reflected by a decrease in heart rate and peak systolic pressure. Further reductions in coronary blood flow resulted in inhibition of glycolysis, a greater decrease in tissue levels of high-energy phosphates, and higher tissue levels of both lactate and H+. These changes in glycolytic flux, tissue metabolites, and ventricular performance were proportional to the degree of restriction in coronary blood flow. The importance of coronary blood flow and washout of the interstitial space in the maintenance of accelerated glycolytic flux in oxygen-deficient hearts is emphasized. It is concluded that acceleration of ATP production from glycolysis can occur only in the marginally ischemic tissue in the peripheral area of tissue supplied by an occluded artery. The central area of tissue which receives a low rate of coronary blood flow will have a reduced rate of ATP production due to both a lack of oxygen and an inhibition of glycolysis."}
{"id": "PMID:157", "title": "Mechanisms of glycolytic inhibition in ischemic rat hearts.", "content": "The mechanisms of glycolytic inhibition in ischemic myocardium were investigated in the isolated, perfused rat heart. Glycolysis was inhibited at the level of glyceraldehyde-3-phosphate dehydrogenase. The major factors that accounted for the glycolytic inhibition in the ischemic heart compared with the anoxic heart appeared to be higher tissue levels of lactate and H+ in the ischemic tissue. Increased extracellular pH inhibited glycolysis in anoxic and hypoxic hearts much more readily than it did in aerobic hearts. However, maintenance of both extracellular and intracellular pH caused only a modest acceleration of glycolysis in ischemic hearts. Accumulation of tissue lactate and inhibition of glycolysis were directly proportional to the reduction in coronary bloow flow in both anoxic and ischemic hearts. At intracellular lactate concentrations between 15 and 20 mM, glycolysis was inhibited under both conditions. Addition of either 10, 20, or 40 mM lactate to the perfusate inhibited glycolysis in aerobic, anoxic, and ischemic hearts. The effect of lactate did not appear to be mediated through changes in intracellular pH. It is concluded that accumulation of lactate represents a major factor in the inhibition of glycolysis that develops in ischemic hearts.", "contents": "Mechanisms of glycolytic inhibition in ischemic rat hearts. The mechanisms of glycolytic inhibition in ischemic myocardium were investigated in the isolated, perfused rat heart. Glycolysis was inhibited at the level of glyceraldehyde-3-phosphate dehydrogenase. The major factors that accounted for the glycolytic inhibition in the ischemic heart compared with the anoxic heart appeared to be higher tissue levels of lactate and H+ in the ischemic tissue. Increased extracellular pH inhibited glycolysis in anoxic and hypoxic hearts much more readily than it did in aerobic hearts. However, maintenance of both extracellular and intracellular pH caused only a modest acceleration of glycolysis in ischemic hearts. Accumulation of tissue lactate and inhibition of glycolysis were directly proportional to the reduction in coronary bloow flow in both anoxic and ischemic hearts. At intracellular lactate concentrations between 15 and 20 mM, glycolysis was inhibited under both conditions. Addition of either 10, 20, or 40 mM lactate to the perfusate inhibited glycolysis in aerobic, anoxic, and ischemic hearts. The effect of lactate did not appear to be mediated through changes in intracellular pH. It is concluded that accumulation of lactate represents a major factor in the inhibition of glycolysis that develops in ischemic hearts."}
{"id": "PMID:158", "title": "Comparison of contractile performance of canine atrial and ventricular muscles.", "content": "This study compared the contractile performance of a canine right atrial trabecula with that of a macroscopically indistinguishable trabecula isolated from the right ventricular apex. The heart was removed from nine mongrel puppies weighing 6-8 kg and placed in Krebs-Ringer's bicarbonate solution. The bathing solution contained only 1.25 mmoles of Ca2+ and was bubbled with a 95% O2-5% CO2 gas mixture. Each atrial trabecula was specially selected from the right atrial appendage. Histologically, these trabeculae showed a remarkable longitudinal orientation of the fibers. At Lmax (the length of the muscle at which developed tension was maximum) under identical conditions of temperature, rate of stimulation, ionic milieu, pH, and O2 and CO2 supply, right atrial trabeculae achieved the same developed and total tensions but in a much shorter time than did ventricular trabeculae. In both muscle groups the maximum developed tension averaged about 2.5 g/mm2. Since Lo (expressed as a fraction of Lmax) was less in atrial muscle than it was in ventribular muscle, we concluded that atrial muscle can be stretched considerably more than can ventricular muscle before optimum length is reached. At any given initial muscle length, the maximum of tension rise for atrial trabeculae amounted to at least twice that for ventricular trabeculae. At any given load up to 1.5 g/mm2, the maximum velocity of shortening of an atrial trabecula was about three to four times that of a ventricular trabecula. These results collectively indicate that the contractile performance of the right atrial muscle is in many respects superior to that of the right ventricle, at least under the conditions of these experiments.", "contents": "Comparison of contractile performance of canine atrial and ventricular muscles. This study compared the contractile performance of a canine right atrial trabecula with that of a macroscopically indistinguishable trabecula isolated from the right ventricular apex. The heart was removed from nine mongrel puppies weighing 6-8 kg and placed in Krebs-Ringer's bicarbonate solution. The bathing solution contained only 1.25 mmoles of Ca2+ and was bubbled with a 95% O2-5% CO2 gas mixture. Each atrial trabecula was specially selected from the right atrial appendage. Histologically, these trabeculae showed a remarkable longitudinal orientation of the fibers. At Lmax (the length of the muscle at which developed tension was maximum) under identical conditions of temperature, rate of stimulation, ionic milieu, pH, and O2 and CO2 supply, right atrial trabeculae achieved the same developed and total tensions but in a much shorter time than did ventricular trabeculae. In both muscle groups the maximum developed tension averaged about 2.5 g/mm2. Since Lo (expressed as a fraction of Lmax) was less in atrial muscle than it was in ventribular muscle, we concluded that atrial muscle can be stretched considerably more than can ventricular muscle before optimum length is reached. At any given initial muscle length, the maximum of tension rise for atrial trabeculae amounted to at least twice that for ventricular trabeculae. At any given load up to 1.5 g/mm2, the maximum velocity of shortening of an atrial trabecula was about three to four times that of a ventricular trabecula. These results collectively indicate that the contractile performance of the right atrial muscle is in many respects superior to that of the right ventricle, at least under the conditions of these experiments."}
{"id": "PMID:159", "title": "Serum lactate dehydrogenase activity ratios with different substrates.", "content": "1. The lactate dehydrogenase activity of 89 sera from patients suffering myocardial infarction and of 55 sera from patients with hepatocellular damage was assayed under optimal conditions using pyruvate, alpha-oxobutyrate, hydroxypyruvate and glyoxylate as substrates. Activity was also measured with lactate as substrate at different pH values. 2. The ratios of activities under these different assay conditions were calculated for both series of patients. Correct differentiations for single ratios ranged from virtually nil for hydroxypyruvate/alpha-oxobutyrate to is greater than 93 per cent for glyoxylate/hydroxypyruvate and glyoxylate/alpha-oxobutyrate. This was little improved by the use of multiple ratios involving up to seven separate assays. 3. The activity ratio of hydroxypyruvate to pyruvate which is consistently greater than unity was found to be inverted in a case of morphine poisoning.", "contents": "Serum lactate dehydrogenase activity ratios with different substrates. 1. The lactate dehydrogenase activity of 89 sera from patients suffering myocardial infarction and of 55 sera from patients with hepatocellular damage was assayed under optimal conditions using pyruvate, alpha-oxobutyrate, hydroxypyruvate and glyoxylate as substrates. Activity was also measured with lactate as substrate at different pH values. 2. The ratios of activities under these different assay conditions were calculated for both series of patients. Correct differentiations for single ratios ranged from virtually nil for hydroxypyruvate/alpha-oxobutyrate to is greater than 93 per cent for glyoxylate/hydroxypyruvate and glyoxylate/alpha-oxobutyrate. This was little improved by the use of multiple ratios involving up to seven separate assays. 3. The activity ratio of hydroxypyruvate to pyruvate which is consistently greater than unity was found to be inverted in a case of morphine poisoning."}
{"id": "PMID:160", "title": "Fluorometric assay for N-acetylprocainamide.", "content": "We describe a simple, rapid fluorometric assay for separate quantitative analysis of procainamide and N-acetylprocainamide in mixtures. The effective lenear range (fluorescence vs. concentration) in serum is 0.1 to 10.0 mg/liter, regardless of the ratio (by weight) of the two drugs from 1:10 to 10:1. Analytical recoveries by the extraction method used were 100.0 +/- 3.0% and 98.0 +/- 4.0%, respectively. For determination of either compound, the maximum coefficient of variation was 10%.", "contents": "Fluorometric assay for N-acetylprocainamide. We describe a simple, rapid fluorometric assay for separate quantitative analysis of procainamide and N-acetylprocainamide in mixtures. The effective lenear range (fluorescence vs. concentration) in serum is 0.1 to 10.0 mg/liter, regardless of the ratio (by weight) of the two drugs from 1:10 to 10:1. Analytical recoveries by the extraction method used were 100.0 +/- 3.0% and 98.0 +/- 4.0%, respectively. For determination of either compound, the maximum coefficient of variation was 10%."}
{"id": "PMID:161", "title": "Rapid kinetic measurement of lactate in plasma with a centrifugal analyzer.", "content": "In this method, blood is collected in ammonium heparinized microhematocrit tubes and lactate is directly determined in the plasma, separated within 15 min from the erythrocytes. Lactate is assayed by mixing 10 mul of sample with NAD+ and lactate dehydrogenase in tris(hydroxymethyl)aminomethane hydrazine buffer. The rate of increase in absorbance of the NADH formed, measured at 340 nm, is proportional to lactate concentration. The assay is complete in 4 min and absorbance is linearly related to concentration from 0.625 to 15 mmol/liter. Analytical recoveries of lactate added to plasma averaged 104% (range, 91-116%). Results compared well for plasma samples analyzed by this method with the CentrifiChem and the Du Pont aca.", "contents": "Rapid kinetic measurement of lactate in plasma with a centrifugal analyzer. In this method, blood is collected in ammonium heparinized microhematocrit tubes and lactate is directly determined in the plasma, separated within 15 min from the erythrocytes. Lactate is assayed by mixing 10 mul of sample with NAD+ and lactate dehydrogenase in tris(hydroxymethyl)aminomethane hydrazine buffer. The rate of increase in absorbance of the NADH formed, measured at 340 nm, is proportional to lactate concentration. The assay is complete in 4 min and absorbance is linearly related to concentration from 0.625 to 15 mmol/liter. Analytical recoveries of lactate added to plasma averaged 104% (range, 91-116%). Results compared well for plasma samples analyzed by this method with the CentrifiChem and the Du Pont aca."}
{"id": "PMID:162", "title": "Improved high-resolution high-voltage paper electrophoresis system for use in screening for aminoacidopathies.", "content": "High-voltage paper electrophoresis of small samples of serum and urine at pH 6.0 resolves basic and acidic amino acids and separates them from the neutral amino acids. For separation and identification of the neutral amino acids, the appropriate area of the electrophoretogram is cut out, sewn onto a second sheet of paper, and rerun at pH 1.9. By this method, amino acids are rapidly resolved. It is suited for use with special procedures such as oxidation of biological fluid with performic acid and specific staining for confirmation of amino acid identification.", "contents": "Improved high-resolution high-voltage paper electrophoresis system for use in screening for aminoacidopathies. High-voltage paper electrophoresis of small samples of serum and urine at pH 6.0 resolves basic and acidic amino acids and separates them from the neutral amino acids. For separation and identification of the neutral amino acids, the appropriate area of the electrophoretogram is cut out, sewn onto a second sheet of paper, and rerun at pH 1.9. By this method, amino acids are rapidly resolved. It is suited for use with special procedures such as oxidation of biological fluid with performic acid and specific staining for confirmation of amino acid identification."}
{"id": "PMID:165", "title": "A clinical method for the determination of serum gamma-glutamyl transpeptidase.", "content": "A simple, highly sensitive and reproducible method for the assay of gamma-glutamyl transpeptidase (EC 2.3.2-) activity is introduced, using gamma-glutamyl-p-nitroanilide as a substrate and glycylglycine as an acceptor in 50 g/l of polyoxyethylene nonylphenol. Serum transpeptidase activity was assayed in 1080 healthy adults, the normal mean value being 14.8 mU/ml. The diagnostic evaluation of the enzyme in various hepatobiliary diseases is also discussed.", "contents": "A clinical method for the determination of serum gamma-glutamyl transpeptidase. A simple, highly sensitive and reproducible method for the assay of gamma-glutamyl transpeptidase (EC 2.3.2-) activity is introduced, using gamma-glutamyl-p-nitroanilide as a substrate and glycylglycine as an acceptor in 50 g/l of polyoxyethylene nonylphenol. Serum transpeptidase activity was assayed in 1080 healthy adults, the normal mean value being 14.8 mU/ml. The diagnostic evaluation of the enzyme in various hepatobiliary diseases is also discussed."}
{"id": "PMID:167", "title": "Treatment of renal hypertension.", "content": "There are different types of renal hypertension: hypertension due to parenchymal renal disease, renovascular hypertension, hypertension due to urological disease, hypertension of endstage renal disease. Treatment has to consider-above all-the possibility of specific, medical or surgical procedures that may cause the underlying condition. If the underlying disease is not amenable to specific therapy, symptomatic medical treatment to lower blood pressure is indicated: besides control of sodium-intake and body weight antihypertensive drugs are generally indicated. We use them, alone or in combination, in the following line of order: diuretics, beta-adrenergic blockers, dihydralazine, reserpine, clonidine, alpha-methyldopa, guanethidine.", "contents": "Treatment of renal hypertension. There are different types of renal hypertension: hypertension due to parenchymal renal disease, renovascular hypertension, hypertension due to urological disease, hypertension of endstage renal disease. Treatment has to consider-above all-the possibility of specific, medical or surgical procedures that may cause the underlying condition. If the underlying disease is not amenable to specific therapy, symptomatic medical treatment to lower blood pressure is indicated: besides control of sodium-intake and body weight antihypertensive drugs are generally indicated. We use them, alone or in combination, in the following line of order: diuretics, beta-adrenergic blockers, dihydralazine, reserpine, clonidine, alpha-methyldopa, guanethidine."}
{"id": "PMID:170", "title": "Anaerobic glycolysis in normal human erythrocytes incubated in vitro with sodium salicylate.", "content": "1. Some effects of sodium salicylate upon anaerobic glycolysis have been studied in normal human erythrocytes incubated for up to 6 h at 37 degrees C in autologous sera. 2. Both glucose consumption and lactate production were stimulated by concentrations of salicylate up to 60 mmol/l but at the highest concentration used (90 mmol/l) an initial stimulus was followed by inhibition of glycolysis. 3. Losses occurred of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and adenosine 5'-phosphate(AMP)at higher concentrations of salicylate and there was a concomitant increase of inorganic phosphate. 4. Other phosphate esters underwent concentration changes at higher concentrations of salicylate that reflected inadequate concentrations of ATP for glycolysis. 5. The rates of sodium efflux from, and potassium influx into, erythrocytes were unaffected by the presence of salicylate at concentrations sufficient to stimulate glycolysis.", "contents": "Anaerobic glycolysis in normal human erythrocytes incubated in vitro with sodium salicylate. 1. Some effects of sodium salicylate upon anaerobic glycolysis have been studied in normal human erythrocytes incubated for up to 6 h at 37 degrees C in autologous sera. 2. Both glucose consumption and lactate production were stimulated by concentrations of salicylate up to 60 mmol/l but at the highest concentration used (90 mmol/l) an initial stimulus was followed by inhibition of glycolysis. 3. Losses occurred of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and adenosine 5'-phosphate(AMP)at higher concentrations of salicylate and there was a concomitant increase of inorganic phosphate. 4. Other phosphate esters underwent concentration changes at higher concentrations of salicylate that reflected inadequate concentrations of ATP for glycolysis. 5. The rates of sodium efflux from, and potassium influx into, erythrocytes were unaffected by the presence of salicylate at concentrations sufficient to stimulate glycolysis."}
{"id": "PMID:171", "title": "Arterial catecholamines in hypoxic exercise in man.", "content": "1. We measured the minute ventilation and arterial blood catecholamine concentrations in four normal men standing and at two levels of moderate treadmill exercise breathing 14% oxygen or air. 2. Minute ventilation was significantly higher during hypoxic exercise than during normoxic exercise at an oxygen uptake of 1500 ml/min. 3. Arterial plasma noradrenaline during hypoxic exercise at an oxygen uptake of 1500 ml/min was significantly greater than at rest. 4. Arterial plasma noradrenaline during normoxic exercise at an oxygen uptake of 1500 ml/min was not elevated above the resting concentration. 5. The results are compatible with the suggestion that increased concentrations of arterial plasma noradrenaline contribute to the hypoxic potentiation of the respiratory response to moderate exercise.", "contents": "Arterial catecholamines in hypoxic exercise in man. 1. We measured the minute ventilation and arterial blood catecholamine concentrations in four normal men standing and at two levels of moderate treadmill exercise breathing 14% oxygen or air. 2. Minute ventilation was significantly higher during hypoxic exercise than during normoxic exercise at an oxygen uptake of 1500 ml/min. 3. Arterial plasma noradrenaline during hypoxic exercise at an oxygen uptake of 1500 ml/min was significantly greater than at rest. 4. Arterial plasma noradrenaline during normoxic exercise at an oxygen uptake of 1500 ml/min was not elevated above the resting concentration. 5. The results are compatible with the suggestion that increased concentrations of arterial plasma noradrenaline contribute to the hypoxic potentiation of the respiratory response to moderate exercise."}
{"id": "PMID:168", "title": "Effects of graded infusions of monomethylmethacrylate on coagulation, blood lipids, respiration and circulation. An experimental study in dogs.", "content": "In 4 dogs injected intravenously (i.v.) with 125I labeled fibrinogen, 51Cr labeled platelets and 99mTc labeled albumin, and subjected to successively increasing amounts of i.v. infused monomethylmethacrylate, doses corresponding to the amounts released into the blood stream following implantation of acrylic cement during total hip replacements did not affect the clotting mechanism, did not cause trapping of platelets and fibrin in the lungs, did not generate fat emboli, and did not cause depression of the arterial oxygen tension or blood pressure. Monomethylmethacrylate in whole blood was associated with both blood cells and plasma.", "contents": "Effects of graded infusions of monomethylmethacrylate on coagulation, blood lipids, respiration and circulation. An experimental study in dogs. In 4 dogs injected intravenously (i.v.) with 125I labeled fibrinogen, 51Cr labeled platelets and 99mTc labeled albumin, and subjected to successively increasing amounts of i.v. infused monomethylmethacrylate, doses corresponding to the amounts released into the blood stream following implantation of acrylic cement during total hip replacements did not affect the clotting mechanism, did not cause trapping of platelets and fibrin in the lungs, did not generate fat emboli, and did not cause depression of the arterial oxygen tension or blood pressure. Monomethylmethacrylate in whole blood was associated with both blood cells and plasma."}
{"id": "PMID:210", "title": "Influence of pH and hypoxia on the success of defibrillation.", "content": "Clinical impressions about the problem of defibrillation during states of acid-base imbalance and hypoxia have been influenced by studies involving the effect of these derangements on the ventricular fibrillation threshold. Based on body weight, energy requirements for defibrillation in normal dogs were compared to requirements in dogs subjected to commonly encountered acid-base disturbances and severe hypoxemia. No significant differences were found. Seventy-five percent of all animals in the study were electrically converted with low-to-moderate levels of energy. The incidence of spontaneous resumption of circulation following defibrillation was lowest in animals subjected to metabolic acidosis and hypoxia. The results suggest that pH and blood gas alterations, previously shown to influence the normal ventricular fibrillation threshold, do not significantly affect the normal defibrillation threshold.", "contents": "Influence of pH and hypoxia on the success of defibrillation. Clinical impressions about the problem of defibrillation during states of acid-base imbalance and hypoxia have been influenced by studies involving the effect of these derangements on the ventricular fibrillation threshold. Based on body weight, energy requirements for defibrillation in normal dogs were compared to requirements in dogs subjected to commonly encountered acid-base disturbances and severe hypoxemia. No significant differences were found. Seventy-five percent of all animals in the study were electrically converted with low-to-moderate levels of energy. The incidence of spontaneous resumption of circulation following defibrillation was lowest in animals subjected to metabolic acidosis and hypoxia. The results suggest that pH and blood gas alterations, previously shown to influence the normal ventricular fibrillation threshold, do not significantly affect the normal defibrillation threshold."}
{"id": "PMID:218", "title": "Pleural effusion associated with aortitis syndrome.", "content": "A patient with aortitis syndrome had a pleural effusion which subsided but reappeared with an exacerbation of aortitis symptoms while under antituberculosis treatment. The character of the fluid was that of an exudate, and the glucose concentration was normal. Clinical and laboratory features of the case suggest that the effusion was part of the aortitis syndrome per se.", "contents": "Pleural effusion associated with aortitis syndrome. A patient with aortitis syndrome had a pleural effusion which subsided but reappeared with an exacerbation of aortitis symptoms while under antituberculosis treatment. The character of the fluid was that of an exudate, and the glucose concentration was normal. Clinical and laboratory features of the case suggest that the effusion was part of the aortitis syndrome per se."}
{"id": "PMID:220", "title": "[Transplantation and preservation of tissue-typized skin in burns].", "content": "At the Department of Plastic Surgery and Burns, Berufsgenossenschaftliche Unfalklinik Ludwigshafen-Oggersheim, a skinbank with typed skin has been established. The storage system consists of deep-freezing at -196 degrees C in liquid nitrogen. The transplantation of HL-A typed skin was evaluated from the clinical and histological point of view. Due to the effort necessary for such an undertaking this method is critically reviewed.", "contents": "[Transplantation and preservation of tissue-typized skin in burns]. At the Department of Plastic Surgery and Burns, Berufsgenossenschaftliche Unfalklinik Ludwigshafen-Oggersheim, a skinbank with typed skin has been established. The storage system consists of deep-freezing at -196 degrees C in liquid nitrogen. The transplantation of HL-A typed skin was evaluated from the clinical and histological point of view. Due to the effort necessary for such an undertaking this method is critically reviewed."}
{"id": "PMID:226", "title": "Charge properties of human pituitary and amniotic fluid prolactins.", "content": "The apparent isoelectric points (pI) in isoelectric focusing (IF) of human pituitary and amniotic fluid prolactin (hPRL), both non-iodinated and iodinated, were determined. Unresolved mixtures of pituitary hPRL isohormones E and F, and of at least five isohormones found in amniotic fluid, and plasma hPRL exhibit an average pI value of 6.5 - 6.7. Transient state pH values observed or previously reported for hPRL components range from pH 5.9 to 6.8 after correction to standard conditions. At pH 8.1, the major isohormone, hPRL-F, carriers a charge of 2.2 net protons per molecule. The net charge differences among isohormones E, F and G are compatible with acquisition or loss of single charged groups per 20,000 molecular weight. This net charge is similar to that of the least prolactin-bioactive major isohormone of human growth hormone (hGH-B), while the hGH with a bioactivity comparable to that of hPRL exhibits a net charge of 3.4 valence units. The \"large\" isohormones J and H increased net charges, by a factor of 2-3, in direct proportion to their size increments.", "contents": "Charge properties of human pituitary and amniotic fluid prolactins. The apparent isoelectric points (pI) in isoelectric focusing (IF) of human pituitary and amniotic fluid prolactin (hPRL), both non-iodinated and iodinated, were determined. Unresolved mixtures of pituitary hPRL isohormones E and F, and of at least five isohormones found in amniotic fluid, and plasma hPRL exhibit an average pI value of 6.5 - 6.7. Transient state pH values observed or previously reported for hPRL components range from pH 5.9 to 6.8 after correction to standard conditions. At pH 8.1, the major isohormone, hPRL-F, carriers a charge of 2.2 net protons per molecule. The net charge differences among isohormones E, F and G are compatible with acquisition or loss of single charged groups per 20,000 molecular weight. This net charge is similar to that of the least prolactin-bioactive major isohormone of human growth hormone (hGH-B), while the hGH with a bioactivity comparable to that of hPRL exhibits a net charge of 3.4 valence units. The \"large\" isohormones J and H increased net charges, by a factor of 2-3, in direct proportion to their size increments."}
{"id": "PMID:227", "title": "Human and monkey prolactin and growth hormone: separation of polymorphic forms by isoelectric focusing.", "content": "The feasibility of using isoelectric focusing for the separation of primate pituitary growth hormone from prolactin and for the characterization of polymorphic forms of these hormones was explored. In a pH 3--10 gradient, extracts of both human and cynomolgus monkey pituitaries were each resolved into 4 growth hormone components and at least 3 prolactin components, as shown by radioimmunoassay. In narrower gradients (of 2--3 pH units) greater resolution was achieved; the principal growth hormone components were well separated from the principal prolactin components but there was overlapping of some minor components. A partially purified human prolactin preparation was found to contain 4 prolactin components, one of which had a prolactin/growth hormone ratio of 760. Clinical grade human growth hormone was also resolved into at least 5 prolactin and 5 growth hormone components, many of which had higher pI values than those found in pituitary extract. Under the conditions used, both growth hormone and prolactin were found to be polymorphic with respect to isoelectric point. Some of the human prolactin components were found to contain less than 0.2% growth hormone by radioimmunoassay. Monkey growth hormone containing 0.01% prolactin was isolated. These findings demonstrate that isoelectric focusing is useful for the preparation of both growth hormone and prolactin which are essentially free of one another. Furthermore, the polymorphic forms were repeatedly found in preparations obtained by several methods and from 2 different species, suggesting that these forms are not artifacts.", "contents": "Human and monkey prolactin and growth hormone: separation of polymorphic forms by isoelectric focusing. The feasibility of using isoelectric focusing for the separation of primate pituitary growth hormone from prolactin and for the characterization of polymorphic forms of these hormones was explored. In a pH 3--10 gradient, extracts of both human and cynomolgus monkey pituitaries were each resolved into 4 growth hormone components and at least 3 prolactin components, as shown by radioimmunoassay. In narrower gradients (of 2--3 pH units) greater resolution was achieved; the principal growth hormone components were well separated from the principal prolactin components but there was overlapping of some minor components. A partially purified human prolactin preparation was found to contain 4 prolactin components, one of which had a prolactin/growth hormone ratio of 760. Clinical grade human growth hormone was also resolved into at least 5 prolactin and 5 growth hormone components, many of which had higher pI values than those found in pituitary extract. Under the conditions used, both growth hormone and prolactin were found to be polymorphic with respect to isoelectric point. Some of the human prolactin components were found to contain less than 0.2% growth hormone by radioimmunoassay. Monkey growth hormone containing 0.01% prolactin was isolated. These findings demonstrate that isoelectric focusing is useful for the preparation of both growth hormone and prolactin which are essentially free of one another. Furthermore, the polymorphic forms were repeatedly found in preparations obtained by several methods and from 2 different species, suggesting that these forms are not artifacts."}
{"id": "PMID:229", "title": "Ecological observation of the 137Cs-contamination in beef of animals from the southern-Bavarian area.", "content": "Certain climatic and edaphic conformations in the Bavarian sub-alpine mountains and in the Alps favor above all the development of a land utilization system and farm structures similar to those in the northern part of Scandinavia. In 1963/64, the years of the highest environmental contamination up to the present, we established in 600 beef samples from the round or shoulder of male and female cattle (mainly Highland cattle) close connections between the 137Cs-contamination of green crop and the long lastnig yearly precipitation quantities, as well as certain relations between the 137Cs-contamination of meat and differences in the feeding and keeping of the animals. During summer-seasons (April-October), beef of cattle from pastures with heavy rainfall (Alps) was contaiminated by 137Cs up to 15 times more than that of confined animals. Hereby the rate of 137Cs-contamination in the meat of grazing cattle was nearly proportional to the quantities of precipitation. When confined cattle were fed on pastures in autumn after harvesting for 2 to 3 weeks, a quick increase of 137Cs-contamination of the meat was caused within this time up to values which in this district were otherwise only observed in grazing cattle. The lower 137Cs-content in meat of cattle housed during the summer season is due to the more varied fodder, which is at that time less contaminated than green crop. During the winter season (November to March), the highest contaminations in the meat of confined (Bohemian Forest) or grazing cattle (Alps) was measured when the animals in these districts were almost exclusively fed with fodder from the own farmground or with leafy silage. The highest contamination was almost regularly noticed in January, February and March, as generally during these months the highly contaminated first cut hay is fed. Here the meat was often even more contaminated than that of grazing cattle. After the quick decrease of 137Cs in fallout noticed in the years 1964 and 1965, in 1965/66 a dependance in the 137Cs-contamination of beef on the methods of keeping and feeding could still be observed in only the extreme cases (Alps, Bavarian- and Bohemian Forest); though in general, meat of animals from districts with heavy rainfall was slightly more contaminated than meat of animals from regions with less precipitation.", "contents": "Ecological observation of the 137Cs-contamination in beef of animals from the southern-Bavarian area. Certain climatic and edaphic conformations in the Bavarian sub-alpine mountains and in the Alps favor above all the development of a land utilization system and farm structures similar to those in the northern part of Scandinavia. In 1963/64, the years of the highest environmental contamination up to the present, we established in 600 beef samples from the round or shoulder of male and female cattle (mainly Highland cattle) close connections between the 137Cs-contamination of green crop and the long lastnig yearly precipitation quantities, as well as certain relations between the 137Cs-contamination of meat and differences in the feeding and keeping of the animals. During summer-seasons (April-October), beef of cattle from pastures with heavy rainfall (Alps) was contaiminated by 137Cs up to 15 times more than that of confined animals. Hereby the rate of 137Cs-contamination in the meat of grazing cattle was nearly proportional to the quantities of precipitation. When confined cattle were fed on pastures in autumn after harvesting for 2 to 3 weeks, a quick increase of 137Cs-contamination of the meat was caused within this time up to values which in this district were otherwise only observed in grazing cattle. The lower 137Cs-content in meat of cattle housed during the summer season is due to the more varied fodder, which is at that time less contaminated than green crop. During the winter season (November to March), the highest contaminations in the meat of confined (Bohemian Forest) or grazing cattle (Alps) was measured when the animals in these districts were almost exclusively fed with fodder from the own farmground or with leafy silage. The highest contamination was almost regularly noticed in January, February and March, as generally during these months the highly contaminated first cut hay is fed. Here the meat was often even more contaminated than that of grazing cattle. After the quick decrease of 137Cs in fallout noticed in the years 1964 and 1965, in 1965/66 a dependance in the 137Cs-contamination of beef on the methods of keeping and feeding could still be observed in only the extreme cases (Alps, Bavarian- and Bohemian Forest); though in general, meat of animals from districts with heavy rainfall was slightly more contaminated than meat of animals from regions with less precipitation."}
{"id": "PMID:230", "title": "Liver microsomal beta-glucuronidase and UDP-glucuronyltransferase.", "content": "Both UDP-glucuronyltransferase (GT) and beta-glucuronidase (betaG) were assayed in untreated liver microsomes. Optimum assay conditions were established with rat liver microsomes using p-nitrophenol (pNP) and its glucuronide (pNPGA) at the pH optima of GT (7.5) and betaG (4.5). The activities of the two enzymes were compared using microsomes from rats, mice, pigs, cattle and horses, with pNP, pNPGA, and phenolphthalein as substrate, in the presence of various cofactors and inhibitors at pH 7.5 and 4.5. These data disclose pronounced differences with respect to species, substrate and other experimental conditions, thereby precluding the establishment of general optimum conditions. The two enzymes were also assayed under strictly identical conditions using pNP and pNPGA and rat liver microsomes at pH 7.5 in the presence and absence of UDP-glucuronate disodium (UDPGA), activators (ATP;UDP-N-acetylglucosamine) and inhibitors. When provided with a functional level of UDPGA, both enzymes proved active under those conditions, and a conjugation-deconjugation interplay was indicated. The two processes could be selectively and totally inhibited by Zn2+ and saccharolactone. The results suggest that conjugation-deconjugation-reconjugation cycles may be operative in the metabolism of drugs in vivo, taking place already at the level of the liver endoplasmic reticulum.", "contents": "Liver microsomal beta-glucuronidase and UDP-glucuronyltransferase. Both UDP-glucuronyltransferase (GT) and beta-glucuronidase (betaG) were assayed in untreated liver microsomes. Optimum assay conditions were established with rat liver microsomes using p-nitrophenol (pNP) and its glucuronide (pNPGA) at the pH optima of GT (7.5) and betaG (4.5). The activities of the two enzymes were compared using microsomes from rats, mice, pigs, cattle and horses, with pNP, pNPGA, and phenolphthalein as substrate, in the presence of various cofactors and inhibitors at pH 7.5 and 4.5. These data disclose pronounced differences with respect to species, substrate and other experimental conditions, thereby precluding the establishment of general optimum conditions. The two enzymes were also assayed under strictly identical conditions using pNP and pNPGA and rat liver microsomes at pH 7.5 in the presence and absence of UDP-glucuronate disodium (UDPGA), activators (ATP;UDP-N-acetylglucosamine) and inhibitors. When provided with a functional level of UDPGA, both enzymes proved active under those conditions, and a conjugation-deconjugation interplay was indicated. The two processes could be selectively and totally inhibited by Zn2+ and saccharolactone. The results suggest that conjugation-deconjugation-reconjugation cycles may be operative in the metabolism of drugs in vivo, taking place already at the level of the liver endoplasmic reticulum."}
{"id": "PMID:231", "title": "Biochemical aspects of renal ammonia formation in metabolic acidosis.", "content": "In omnivorous creatures, the diet is acidogenic, especially as a result of the meat content, which gives rise to phosphoric and sulphuric acids, i.e., to metabolic acidosis. In the short term, metabolic acids are buffered by tissue proteins and bicarbonate (the 'alkali reserve'). In the longer term, acid must be excreted, or neutralized with base which is also generated from the diet, by conversion of dietary amino-nitrogen to ammonia. The final steps of this process occur in the kidney, which converts circulating glutamine to ammonia, and to carbon products such as glucose and carbon dioxide, by metabolic reactions which adapt during acidosis to generate more ammonia and maintain an increased renal ammonia content. The complex mechanisms which govern the formation of ammonia, glucose and carbon dioxide from glutamine, involving the reactions of amino acids, the tricarboxylic acid cycle, and gluconeogenesis, are reviewed.", "contents": "Biochemical aspects of renal ammonia formation in metabolic acidosis. In omnivorous creatures, the diet is acidogenic, especially as a result of the meat content, which gives rise to phosphoric and sulphuric acids, i.e., to metabolic acidosis. In the short term, metabolic acids are buffered by tissue proteins and bicarbonate (the 'alkali reserve'). In the longer term, acid must be excreted, or neutralized with base which is also generated from the diet, by conversion of dietary amino-nitrogen to ammonia. The final steps of this process occur in the kidney, which converts circulating glutamine to ammonia, and to carbon products such as glucose and carbon dioxide, by metabolic reactions which adapt during acidosis to generate more ammonia and maintain an increased renal ammonia content. The complex mechanisms which govern the formation of ammonia, glucose and carbon dioxide from glutamine, involving the reactions of amino acids, the tricarboxylic acid cycle, and gluconeogenesis, are reviewed."}
{"id": "PMID:232", "title": "Studies on the mechanism of the changes in serum and liver gamma-glutamyl transpeptidase activity. I. Experimental extrahepatic cholestasis in rabbits.", "content": "Serum, liver and renal gamma-glutamyl transpeptidase (GGT) activities were studied in four groups of rabbits: controls, rabbits with obstructive extrahepatic cholestasis, rabbits with obstructive anuria, and animals with combined obstructive extrahepatic cholestasis and obstructive anuria. Serum GGT was essentially increased in rabbits with obstructive extrahepatic cholestasis, showing peak values in the combined cholestasis + obstructive anuria group, and practically normal values in animals with anuria. Liver GGT was increased in both cholestasis groups, but the increase was less prominent than the increase in serum GGT and there was no correlation between them. In both anuric groups renal GGT was reduced, probably as a result of inhibited enzyme synthesis secondary to the altered conditions for adequate renal function. The results obtained are suggestive of a probable renal involvement in the formation of the serum GGT activity level.", "contents": "Studies on the mechanism of the changes in serum and liver gamma-glutamyl transpeptidase activity. I. Experimental extrahepatic cholestasis in rabbits. Serum, liver and renal gamma-glutamyl transpeptidase (GGT) activities were studied in four groups of rabbits: controls, rabbits with obstructive extrahepatic cholestasis, rabbits with obstructive anuria, and animals with combined obstructive extrahepatic cholestasis and obstructive anuria. Serum GGT was essentially increased in rabbits with obstructive extrahepatic cholestasis, showing peak values in the combined cholestasis + obstructive anuria group, and practically normal values in animals with anuria. Liver GGT was increased in both cholestasis groups, but the increase was less prominent than the increase in serum GGT and there was no correlation between them. In both anuric groups renal GGT was reduced, probably as a result of inhibited enzyme synthesis secondary to the altered conditions for adequate renal function. The results obtained are suggestive of a probable renal involvement in the formation of the serum GGT activity level."}
{"id": "PMID:233", "title": "Studies on the mechanism of the changes in serum and liver gamma-glutamyl transpeptidase activity. II. Experimental hexachlorobenzene porphyria in rabbits.", "content": "The mechanism responsible for the changes in serum and liver gamma-glutamyl transpeptidase (gamma-GT) activity was studied in a model of experimental hexachlorobenzene porphyria in rabbits. Porphyria followed the administration of hexachlorobenzene in doses of 280 mumol - kg-1 body weight, which were given daily through a gastric tube over a 20-day period. Serum gamma-GT activity and the activities of the lysosomal enzymes beta-N-acetylglucosaminidase and alpha-mannosidase were increased, whereas L-aspartate: 2-oxoglutarate aminotransferase and L-alanine: 2-oxoglutarate aminotransferase and L-alanine: 2-oxoglutarate aminotransferase remained unaltered. There was a considerable increase in liver microsomal protein, gamma-GT, cytochrome P-450, anilinehydroxylase, aminopyrine-demethylase and delta-aminolevulinic acid synthase. In the liver gamma-GT was detected in the microsomes as well as in the cytoplasm where enzymatic activity was higher. The high correlation coefficient between liver gamma-GT, cytochrome P-450 and delta-aminolevulinic acid synthase witnesses a hexachlorobenzene-induced gamma-GT formation in the liver. A statistically significant correlation between serum and liver gamma-GT activity was also found. These data strongly suggest that the increase in serum gamma-GT activity may result from the induction of the enzyme in the liver.", "contents": "Studies on the mechanism of the changes in serum and liver gamma-glutamyl transpeptidase activity. II. Experimental hexachlorobenzene porphyria in rabbits. The mechanism responsible for the changes in serum and liver gamma-glutamyl transpeptidase (gamma-GT) activity was studied in a model of experimental hexachlorobenzene porphyria in rabbits. Porphyria followed the administration of hexachlorobenzene in doses of 280 mumol - kg-1 body weight, which were given daily through a gastric tube over a 20-day period. Serum gamma-GT activity and the activities of the lysosomal enzymes beta-N-acetylglucosaminidase and alpha-mannosidase were increased, whereas L-aspartate: 2-oxoglutarate aminotransferase and L-alanine: 2-oxoglutarate aminotransferase and L-alanine: 2-oxoglutarate aminotransferase remained unaltered. There was a considerable increase in liver microsomal protein, gamma-GT, cytochrome P-450, anilinehydroxylase, aminopyrine-demethylase and delta-aminolevulinic acid synthase. In the liver gamma-GT was detected in the microsomes as well as in the cytoplasm where enzymatic activity was higher. The high correlation coefficient between liver gamma-GT, cytochrome P-450 and delta-aminolevulinic acid synthase witnesses a hexachlorobenzene-induced gamma-GT formation in the liver. A statistically significant correlation between serum and liver gamma-GT activity was also found. These data strongly suggest that the increase in serum gamma-GT activity may result from the induction of the enzyme in the liver."}
{"id": "PMID:234", "title": "Changes in erythrocyte 2,3 diphosphoglycerate in women following short term maximal exercise.", "content": "15 untrained women were subjected to a walking treadmill test to determine the influence of maximal exercise upon synthesis of erythrocyte 2,3 DPG. Although there was a 9.8% increase in the 2,3 DPG content following exercise, there was a concomitant 9.4% increase in the hemoglobin level; therefore, when 2,3 DPG is expressed as a ratio to hemoglobin (See Article), there was no significant change as a result of exercise stress. It was suggested that three additive factors produced during strenuous exercise; decreased pH; increased hemoglobin concentration; and increased CO2 production result in by-product inhibition of 2,3 DPG synthesis. It is concluded that 2,3 DPG does not provide a physiologic benefit in the adaptation of the oxygen transport system to exercise.", "contents": "Changes in erythrocyte 2,3 diphosphoglycerate in women following short term maximal exercise. 15 untrained women were subjected to a walking treadmill test to determine the influence of maximal exercise upon synthesis of erythrocyte 2,3 DPG. Although there was a 9.8% increase in the 2,3 DPG content following exercise, there was a concomitant 9.4% increase in the hemoglobin level; therefore, when 2,3 DPG is expressed as a ratio to hemoglobin (See Article), there was no significant change as a result of exercise stress. It was suggested that three additive factors produced during strenuous exercise; decreased pH; increased hemoglobin concentration; and increased CO2 production result in by-product inhibition of 2,3 DPG synthesis. It is concluded that 2,3 DPG does not provide a physiologic benefit in the adaptation of the oxygen transport system to exercise."}
{"id": "PMID:235", "title": "Hydroxylation of p-Coumaric acid by illuminated chloroplasts. The role of superoxide.", "content": "1. Chloroplasts isolated from leaves of spinach-beet (Beta vulgaris L. ssp. vulgaris) do not catalyse the hydroxylation of p-coumaric acid in the dark unless a reductant (such as ascorbate, NADH or NADPH) is added. Superoxide dismutase has no effect on this reaction. 2. Illuminated chloroplasts catalyse the hydroxylation in the absence of added reductant. This reaction is completely inhibited by superoxide dismutase, but catalase has little effect. 3. Both hydroxylation in the light and hydroxylation in the dark in the presence of reductants are inhibited by diethyldithiocarbamate, EDTA, cyanide and 2-mercaptoethanol. 4. It is proposed that O-2- generated by illuminated chloroplasts is involved in the provision of a reductant to the enzyme phenolase.", "contents": "Hydroxylation of p-Coumaric acid by illuminated chloroplasts. The role of superoxide. 1. Chloroplasts isolated from leaves of spinach-beet (Beta vulgaris L. ssp. vulgaris) do not catalyse the hydroxylation of p-coumaric acid in the dark unless a reductant (such as ascorbate, NADH or NADPH) is added. Superoxide dismutase has no effect on this reaction. 2. Illuminated chloroplasts catalyse the hydroxylation in the absence of added reductant. This reaction is completely inhibited by superoxide dismutase, but catalase has little effect. 3. Both hydroxylation in the light and hydroxylation in the dark in the presence of reductants are inhibited by diethyldithiocarbamate, EDTA, cyanide and 2-mercaptoethanol. 4. It is proposed that O-2- generated by illuminated chloroplasts is involved in the provision of a reductant to the enzyme phenolase."}
{"id": "PMID:236", "title": "Identification of chloride-binding sites in hemoglobin by nuclear-magnetic-resonance quadrupole-relaxation studies of hemoglobin digests.", "content": "35Cl minus-nuclear magnetic resonance (NMR) studies indicate that various digests of human hemoglobin with carboxypeptidase A and B, or a combination of the two, may be used for the identification of chloride binding sites. All the digestion products contain, like hemoglobin itself, at least two classes of binding sites, one of high, the others of low affinity. The pH dependence of the excess linewidth of the 35Cl minus NMR signal indicates that in the simple digests with either carboxypeptidase A or B, chloride is bound with high affinity at or near His-beta146-Asp-beta94 and at or near Val-alpha1-Arg-alpha141. The high-affinity sites show, in the case of the simple digests, a strong oxygen linkage which is lost in the forms digested with both carboxypeptidase A and B; this linkage may thus be correlated to the presence of conformational changes. Organic phosphates, like inositol hexaphosphate, show competition for some of the high-affinity chloride binding sites in hemoglobin and in the simple digests. This competition is likewise lost in the doubly digested hemoglobins.", "contents": "Identification of chloride-binding sites in hemoglobin by nuclear-magnetic-resonance quadrupole-relaxation studies of hemoglobin digests. 35Cl minus-nuclear magnetic resonance (NMR) studies indicate that various digests of human hemoglobin with carboxypeptidase A and B, or a combination of the two, may be used for the identification of chloride binding sites. All the digestion products contain, like hemoglobin itself, at least two classes of binding sites, one of high, the others of low affinity. The pH dependence of the excess linewidth of the 35Cl minus NMR signal indicates that in the simple digests with either carboxypeptidase A or B, chloride is bound with high affinity at or near His-beta146-Asp-beta94 and at or near Val-alpha1-Arg-alpha141. The high-affinity sites show, in the case of the simple digests, a strong oxygen linkage which is lost in the forms digested with both carboxypeptidase A and B; this linkage may thus be correlated to the presence of conformational changes. Organic phosphates, like inositol hexaphosphate, show competition for some of the high-affinity chloride binding sites in hemoglobin and in the simple digests. This competition is likewise lost in the doubly digested hemoglobins."}
{"id": "PMID:237", "title": "The internal-alkaline pH gradient, sensitive to uncoupler and ATPase inhibitor, in growing Clostridium pasteurianum.", "content": "1. The intracellular pH was measured in growing Clostridium pasteurianum with and acid-base equilibrium distribution method. [14C]Dimethyloxazolidinedione, [14]methylamine and [14C]acetic acid were used as \"deltapH-indicators\". During growth the extracellular pH decreased from 7.1 to 5.1; simultaneously the intracellular pH changed from 7.5 to 5.9. Thus, the intracellular pH was more alkaline than the extracellular pH by 0.4 to 0.8 pH-units. 2. This pH gradient (interior alkaline) was abolished by the proton conductor carbonylcyanide m-chlorophenylhydrazone and the ATPase inhibitor N,N'-dicyclohexylcarbodiimide. The pH gradient could not be demonstrated in cells depleted of an energy substrate. These results suggest that the pH gradient is formed by an ATPase-driven extrusion of protons from the cells rather than by a Donnan potential. 3. Growth of the organism was inhibited by low concentrations of both carbonylcyanide m-chlorophenylhydrazone (5 muM) and dicyclohexylcarbodiimide (5 muM). This finding suggests that the pH gradient is essential for the growing cell as it may be required for substrate accumulation and other types of transport processes.", "contents": "The internal-alkaline pH gradient, sensitive to uncoupler and ATPase inhibitor, in growing Clostridium pasteurianum. 1. The intracellular pH was measured in growing Clostridium pasteurianum with and acid-base equilibrium distribution method. [14C]Dimethyloxazolidinedione, [14]methylamine and [14C]acetic acid were used as \"deltapH-indicators\". During growth the extracellular pH decreased from 7.1 to 5.1; simultaneously the intracellular pH changed from 7.5 to 5.9. Thus, the intracellular pH was more alkaline than the extracellular pH by 0.4 to 0.8 pH-units. 2. This pH gradient (interior alkaline) was abolished by the proton conductor carbonylcyanide m-chlorophenylhydrazone and the ATPase inhibitor N,N'-dicyclohexylcarbodiimide. The pH gradient could not be demonstrated in cells depleted of an energy substrate. These results suggest that the pH gradient is formed by an ATPase-driven extrusion of protons from the cells rather than by a Donnan potential. 3. Growth of the organism was inhibited by low concentrations of both carbonylcyanide m-chlorophenylhydrazone (5 muM) and dicyclohexylcarbodiimide (5 muM). This finding suggests that the pH gradient is essential for the growing cell as it may be required for substrate accumulation and other types of transport processes."}
{"id": "PMID:238", "title": "D-alanyl-D-alanine carboxypeptidase in the bacterial form and L-form of Proteus mirabilis.", "content": "Membranes of the bacterial form and the stable and unstable L-forms of Proteus mirabilis contain LD and DD-carboxypeptidase. The DD-carboxypeptidase is inhibited non-competitively by penicillin G. The enzyme of the bacterial form is highly penicillin-sensitive (Ki - 4 X 10(-9) M penicillin G). Inhibition is only partly reversible by treatment with penicillinase or by dialysis against buffer. In contrast, the DD-carboxypeptidase of the unstable L-form, grown in the presence of penicillin, is 175-fold less penicillin-sensitive (Ki = 7 X 10(7) M penicillin G). Inhibition is completely reversed by penicillinase or dialysis. After inhibition by penicillin and subsequent reactivation the penicillin sensitivity of the bacterial DD-carboxtpeptidase is similar to the sensitivity of the enzyme of the unstable L-form. The hypothesis is proposed that P. mirabilis contains two DD-carboxypeptidases of different penicillin sensitivity and with different mechanisms of penicillin binding. Peptidoglycan synthesis in the cell walls of the unstable L-form is probably carried out with the help of only one DD-carboxypeptidase, viz. the completely reactivatable enzyme with the lower penicillin sensitivity.", "contents": "D-alanyl-D-alanine carboxypeptidase in the bacterial form and L-form of Proteus mirabilis. Membranes of the bacterial form and the stable and unstable L-forms of Proteus mirabilis contain LD and DD-carboxypeptidase. The DD-carboxypeptidase is inhibited non-competitively by penicillin G. The enzyme of the bacterial form is highly penicillin-sensitive (Ki - 4 X 10(-9) M penicillin G). Inhibition is only partly reversible by treatment with penicillinase or by dialysis against buffer. In contrast, the DD-carboxypeptidase of the unstable L-form, grown in the presence of penicillin, is 175-fold less penicillin-sensitive (Ki = 7 X 10(7) M penicillin G). Inhibition is completely reversed by penicillinase or dialysis. After inhibition by penicillin and subsequent reactivation the penicillin sensitivity of the bacterial DD-carboxtpeptidase is similar to the sensitivity of the enzyme of the unstable L-form. The hypothesis is proposed that P. mirabilis contains two DD-carboxypeptidases of different penicillin sensitivity and with different mechanisms of penicillin binding. Peptidoglycan synthesis in the cell walls of the unstable L-form is probably carried out with the help of only one DD-carboxypeptidase, viz. the completely reactivatable enzyme with the lower penicillin sensitivity."}
{"id": "PMID:239", "title": "Pigeon-liver NAD kinase. The structural and kinetic basis of regulation of NADPH.", "content": "NAD kinase was purified from pigeon liver by an improved procedure which included chromatography on phosphocellulose. The resultant preparation was homogeneous as judged by gel electrophoresis, but electrofocusing gave indications of heterogeneity. The enzyme appeared to be of molecular weight 270000, and to consist of subunits of molecular weight 34000; it may therefore be an octomer. Kinetic studies over a wide range of substrate concentrations revealed departures from Michaelis-Menten behaviour with the substrate NAD+; these were interpreted tentatively in terms of negative homotropic interactions between identical binding sites, since thermal and chemical inactivation studies revealed no evidence for more than one type of catalytic site. The significance of the kinetics and of the type of inhibition produced by NADPH is discussed in terms of the regulation of NAD kinase activity in vivo.", "contents": "Pigeon-liver NAD kinase. The structural and kinetic basis of regulation of NADPH. NAD kinase was purified from pigeon liver by an improved procedure which included chromatography on phosphocellulose. The resultant preparation was homogeneous as judged by gel electrophoresis, but electrofocusing gave indications of heterogeneity. The enzyme appeared to be of molecular weight 270000, and to consist of subunits of molecular weight 34000; it may therefore be an octomer. Kinetic studies over a wide range of substrate concentrations revealed departures from Michaelis-Menten behaviour with the substrate NAD+; these were interpreted tentatively in terms of negative homotropic interactions between identical binding sites, since thermal and chemical inactivation studies revealed no evidence for more than one type of catalytic site. The significance of the kinetics and of the type of inhibition produced by NADPH is discussed in terms of the regulation of NAD kinase activity in vivo."}
{"id": "PMID:240", "title": "Hydrogen ion changes and contractile behavior in the perfused rat heart.", "content": "The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rat. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the 'respiratory' and 'metabolic' alterations affected the contractile behavior to the same extent. In the physiological range studied by us, acidosis depresses and alkalosis increases myocardial contraction. However acidosis seems to depress contractility more than the enhancement produced by the same change in pH towards the alkalotic side. When either amount of shortening or max dl/dt was plotted as a function of hydrogen ion acitvity (aH+) a linear correlation was obtained, either with pure 'metabolic' or 'respiratory' acid-base induced alterations (correlation coefficients higher than -.95; P less than .01). Our findings suggest that in the range studied by us, contraction of the perfused rat heart following acid-base alterations, is a linear function of hydrogen ion activity.", "contents": "Hydrogen ion changes and contractile behavior in the perfused rat heart. The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rat. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the 'respiratory' and 'metabolic' alterations affected the contractile behavior to the same extent. In the physiological range studied by us, acidosis depresses and alkalosis increases myocardial contraction. However acidosis seems to depress contractility more than the enhancement produced by the same change in pH towards the alkalotic side. When either amount of shortening or max dl/dt was plotted as a function of hydrogen ion acitvity (aH+) a linear correlation was obtained, either with pure 'metabolic' or 'respiratory' acid-base induced alterations (correlation coefficients higher than -.95; P less than .01). Our findings suggest that in the range studied by us, contraction of the perfused rat heart following acid-base alterations, is a linear function of hydrogen ion activity."}
{"id": "PMID:241", "title": "Changes of EEG and pulmonary venous admixture during a protein load in patients with cirrhosis.", "content": "21 patients with cirrhosis of the liver and 24 control patients were studied before and after a protein load (120 g protein per day during one week). An EEG was recorded and a visual assessment of frequency pattern was performed. Venous admixture was estimated during hyperoxia. According to the EEG frequency pattern the patient group with cirrhosis was subdivided into those with EEG slowing after the protein load (n = 7) and those without (n = 14). The following results were obtained: 1) Resting arterial blood gases did not change in either group. 2) There was a significant increase of the AaD02 (difference between alveolar p02 and peripheral arterial p02) in cirrhotics and controls. 3) The increase in AaD02 was significantly larger in those cirrhotics showing EEG slowing compared to those without EEG - slowing or to the controls. 4) Fractional venous admisture increased significantly in those cirrhotics showing EEG slowing. There was no significant change in those patients who did not show EEG changes or in the controls.", "contents": "Changes of EEG and pulmonary venous admixture during a protein load in patients with cirrhosis. 21 patients with cirrhosis of the liver and 24 control patients were studied before and after a protein load (120 g protein per day during one week). An EEG was recorded and a visual assessment of frequency pattern was performed. Venous admixture was estimated during hyperoxia. According to the EEG frequency pattern the patient group with cirrhosis was subdivided into those with EEG slowing after the protein load (n = 7) and those without (n = 14). The following results were obtained: 1) Resting arterial blood gases did not change in either group. 2) There was a significant increase of the AaD02 (difference between alveolar p02 and peripheral arterial p02) in cirrhotics and controls. 3) The increase in AaD02 was significantly larger in those cirrhotics showing EEG slowing compared to those without EEG - slowing or to the controls. 4) Fractional venous admisture increased significantly in those cirrhotics showing EEG slowing. There was no significant change in those patients who did not show EEG changes or in the controls."}
{"id": "PMID:250", "title": "An evaluation of factors affecting the in vitro bioassay for erythropoietin.", "content": "Two main aspects of the in vitro mouse foetal liver cell assay for Erythroid Stimulating Factor (ESF) in human sera have been investigated. The haem extraction process has been shown to give specific and quantitative recovery of 59Fe labelled haem from haemoglobin thus confirming that the material assayed in human sera is stimulating the synthesis of this protein. The extraction procedure can be simplified considerably by prior mixing of the reagents without significantly influencing the results. Several serum constituents (citrate, testosterone, B12, folic acid and iron) have been investigated over a range of concentrations for possible effects on the cultures. Generally only small effects on haem synthesis were observed. It is concluded that variations in the levels of these factors in sera from treated patients will not produce any significant alterations in the estimated ESF concentrations.", "contents": "An evaluation of factors affecting the in vitro bioassay for erythropoietin. Two main aspects of the in vitro mouse foetal liver cell assay for Erythroid Stimulating Factor (ESF) in human sera have been investigated. The haem extraction process has been shown to give specific and quantitative recovery of 59Fe labelled haem from haemoglobin thus confirming that the material assayed in human sera is stimulating the synthesis of this protein. The extraction procedure can be simplified considerably by prior mixing of the reagents without significantly influencing the results. Several serum constituents (citrate, testosterone, B12, folic acid and iron) have been investigated over a range of concentrations for possible effects on the cultures. Generally only small effects on haem synthesis were observed. It is concluded that variations in the levels of these factors in sera from treated patients will not produce any significant alterations in the estimated ESF concentrations."}
{"id": "PMID:251", "title": "[Synthesis of N-substituted isoindolines].", "content": "Some derivatives of isoindoline were prepared in order to test their cardiovascular activity. Pharmacological tests showed that some of the compounds had moderate alpha-blocking and coronarodilatory activity whereas others had some local anesthetic activity.", "contents": "[Synthesis of N-substituted isoindolines]. Some derivatives of isoindoline were prepared in order to test their cardiovascular activity. Pharmacological tests showed that some of the compounds had moderate alpha-blocking and coronarodilatory activity whereas others had some local anesthetic activity."}
{"id": "PMID:257", "title": "[Mechanisms of the thermogenic action of noradrenaline during adaptation to cold].", "content": "In white rats both adapted and unadapted to cold, the RQ dynamics during cold exposure, noradrenaline and ganglion blocking agent administration, were studied. The adapted animals' RQ in thermoneutral conditions was shown to be a little higher than in the control rats; 0.5 mg/kg noradrenaline injections induced a clear RQ decrease in the former and did not influence the latters' RQ. Cold exposure was followed by a RQ decrease in both. Ganglion blocking agent administration decreased the RQ in the adapted animals and prevented it from falling in the control those. Noradrenaline is supposed to be the main but not the only factor activating lipolysis in the cold adapted animals.", "contents": "[Mechanisms of the thermogenic action of noradrenaline during adaptation to cold]. In white rats both adapted and unadapted to cold, the RQ dynamics during cold exposure, noradrenaline and ganglion blocking agent administration, were studied. The adapted animals' RQ in thermoneutral conditions was shown to be a little higher than in the control rats; 0.5 mg/kg noradrenaline injections induced a clear RQ decrease in the former and did not influence the latters' RQ. Cold exposure was followed by a RQ decrease in both. Ganglion blocking agent administration decreased the RQ in the adapted animals and prevented it from falling in the control those. Noradrenaline is supposed to be the main but not the only factor activating lipolysis in the cold adapted animals."}
{"id": "PMID:270", "title": "Chromosomal basis of the merozygosity in a partially deploid mutant of Pneumococcus.", "content": "A sulfonamide-resistant mutant of pneumococcus, sulr-c, displays a genetic instability, regularly segregating to wild type. DNA extracts of derivatives of the strain possess transforming activities for both the mutant and wild-type alleles, establishing that the strain is a partial diploid. The linkage of sulr-c to strr-61, a stable chromosomal marker, was established, thus defining a chromosomal locus for sulr-c. DNA isolated from sulr-c cells transforms two mutant recipient strains at the same low efficiency as it does a wild-type recipient, although the mutant property of these strains makes them capable of integrating classical \"low-efficiency\" donor markers equally as efficiently as \"high efficiency\" markers. Hence sulr-c must have a different basis for its low efficiency than do classical low efficiency point mutations. We suggest that the DNA in the region of the sulr-c mutation has a structural abnormality which leads both to its frequent segregation during growth and its difficulty in efficiently mediating genetic transformation.", "contents": "Chromosomal basis of the merozygosity in a partially deploid mutant of Pneumococcus. A sulfonamide-resistant mutant of pneumococcus, sulr-c, displays a genetic instability, regularly segregating to wild type. DNA extracts of derivatives of the strain possess transforming activities for both the mutant and wild-type alleles, establishing that the strain is a partial diploid. The linkage of sulr-c to strr-61, a stable chromosomal marker, was established, thus defining a chromosomal locus for sulr-c. DNA isolated from sulr-c cells transforms two mutant recipient strains at the same low efficiency as it does a wild-type recipient, although the mutant property of these strains makes them capable of integrating classical \"low-efficiency\" donor markers equally as efficiently as \"high efficiency\" markers. Hence sulr-c must have a different basis for its low efficiency than do classical low efficiency point mutations. We suggest that the DNA in the region of the sulr-c mutation has a structural abnormality which leads both to its frequent segregation during growth and its difficulty in efficiently mediating genetic transformation."}
{"id": "PMID:271", "title": "Recombination as a requirement for segregation of a partially diploid mutant of Pneumococcus.", "content": "Conditions are described in which the pneumococcal mutant strain sulr-c, resistant to the drug sulfanilamide, gives rise to sensitive segregants resistant to nitrobenzoic acid at a frequency constant with time. This segregant frequency is markedly enhanced upon exposure of the cells to doses of ultraviolet light or mitomycin C that permit survival of 50% to 90% of the cells. Treatment with acridine orange diminishes the segregant frequency. From the known influences of these three agents on genetic recombination, we propose that a recombination event is necessary in the generation of segregants.--During a period of incubation following treatment with ultraviolet light or mitomycin C, cell division resumes and the original segregant frequency is restored. Thus potential segregants are either unable to replicate in the absence of selection, or they are under-represented among the cells dividing soon after treatment.--If the sulr-c mutation is introduced into a mutant pneumococcal strain lacking an ATP-dependent exonuclease activity and deficient in recombination with transforming DNA, segregant frequencies are unaffected. This fact may indicate limits upon the type of recombination event responsible for segregation.", "contents": "Recombination as a requirement for segregation of a partially diploid mutant of Pneumococcus. Conditions are described in which the pneumococcal mutant strain sulr-c, resistant to the drug sulfanilamide, gives rise to sensitive segregants resistant to nitrobenzoic acid at a frequency constant with time. This segregant frequency is markedly enhanced upon exposure of the cells to doses of ultraviolet light or mitomycin C that permit survival of 50% to 90% of the cells. Treatment with acridine orange diminishes the segregant frequency. From the known influences of these three agents on genetic recombination, we propose that a recombination event is necessary in the generation of segregants.--During a period of incubation following treatment with ultraviolet light or mitomycin C, cell division resumes and the original segregant frequency is restored. Thus potential segregants are either unable to replicate in the absence of selection, or they are under-represented among the cells dividing soon after treatment.--If the sulr-c mutation is introduced into a mutant pneumococcal strain lacking an ATP-dependent exonuclease activity and deficient in recombination with transforming DNA, segregant frequencies are unaffected. This fact may indicate limits upon the type of recombination event responsible for segregation."}
{"id": "PMID:273", "title": "Involvement of the small intestine in systemic mast cell disease.", "content": "A patient is reported with mast cell infiltration of the small intestine in the absence of the skin involvement characteristic of mast cell disease. She also had subtotal villous atrophy responsive to a gluten-free diet. Criteria for diagnosing mast cell disease of the small intestine are proposed. The literature of small intestinal mast cell disease is reviewed and the relationship to coeliac disease is discussed.", "contents": "Involvement of the small intestine in systemic mast cell disease. A patient is reported with mast cell infiltration of the small intestine in the absence of the skin involvement characteristic of mast cell disease. She also had subtotal villous atrophy responsive to a gluten-free diet. Criteria for diagnosing mast cell disease of the small intestine are proposed. The literature of small intestinal mast cell disease is reviewed and the relationship to coeliac disease is discussed."}
{"id": "PMID:274", "title": "Gastric pH and microflora of normal and diarrhoeic infants.", "content": "The microflora and pH of gastric contents were determined in breast-fed and in bottle-fed normal infants, in well nourished infants with acute diarrhoea and in infants with chronic diarrhoea and protein-calorie malnutrition. The last group of infants was reevaluated after recovery from diarrhoea and protein-calorie malnutrition. A bactericidal pH effect below 2-5 was observed. Bottle-fed controls had low pH values and low bacterial concentrations, whereas infants with chronic diarrhoea and protein-calorie malnutrition had high pH values and bacterial overgrowth, essentially of Gram-negative bacilli. After recovery, the only remaining alteration was the frequent isolation of yeast-like fungi in low concentrations. Infants with acute diarrhoea, except for the isolation more frequently of yeast-like fungi, presented no alterations; this seems to indicate that pH alterations and Gram-negative bacilli overgrowth occurred during the evolution of the disease to a chronic state. Breast-fed normal infants had hydrogen-ion concentrations similar to those of the chronic diarrhoea group, but without Gram-negative bacilli overgrowth, suggesting that other factors, besides pH, regulate bacterial growth in the gastric contents of these groups of infants.", "contents": "Gastric pH and microflora of normal and diarrhoeic infants. The microflora and pH of gastric contents were determined in breast-fed and in bottle-fed normal infants, in well nourished infants with acute diarrhoea and in infants with chronic diarrhoea and protein-calorie malnutrition. The last group of infants was reevaluated after recovery from diarrhoea and protein-calorie malnutrition. A bactericidal pH effect below 2-5 was observed. Bottle-fed controls had low pH values and low bacterial concentrations, whereas infants with chronic diarrhoea and protein-calorie malnutrition had high pH values and bacterial overgrowth, essentially of Gram-negative bacilli. After recovery, the only remaining alteration was the frequent isolation of yeast-like fungi in low concentrations. Infants with acute diarrhoea, except for the isolation more frequently of yeast-like fungi, presented no alterations; this seems to indicate that pH alterations and Gram-negative bacilli overgrowth occurred during the evolution of the disease to a chronic state. Breast-fed normal infants had hydrogen-ion concentrations similar to those of the chronic diarrhoea group, but without Gram-negative bacilli overgrowth, suggesting that other factors, besides pH, regulate bacterial growth in the gastric contents of these groups of infants."}
{"id": "PMID:278", "title": "[Biphasic (ulcer-forming and ulcer-preventing) effect of adrenaline in rats].", "content": "Adrenaline-induced gastric ulceration was studied in rats. Adrenaline in high doses caused gastric ulcer, which was completely blocked by pretreatment with alpha-blockers (phenoxybenzamine, dibenamine), but not by pretreatment with propranolol or atropine, nor by vagotomy, hypophysectomy or adrenalectomy. After successive administration of adrenaline, once daily for 7 days, however, no gastric ulcer was observed. Recovery from the ulcerogenic action of adrenaline was seen after 4 weeks withdrawal. Pretreatment with a small dose of adrenaline inhibited the ulcerogenic action of a high dose of adrenaline. Pretreatment with reserpine, pyrogallol or iproniazid inhibited the action of adrenaline. It is concluded that adrenaline has a biphasic effect on gastric ulceration, the ulcerogenic action is due to its alpha-action and antiulcerogenic effect is due to development of tachyphylaxis.", "contents": "[Biphasic (ulcer-forming and ulcer-preventing) effect of adrenaline in rats]. Adrenaline-induced gastric ulceration was studied in rats. Adrenaline in high doses caused gastric ulcer, which was completely blocked by pretreatment with alpha-blockers (phenoxybenzamine, dibenamine), but not by pretreatment with propranolol or atropine, nor by vagotomy, hypophysectomy or adrenalectomy. After successive administration of adrenaline, once daily for 7 days, however, no gastric ulcer was observed. Recovery from the ulcerogenic action of adrenaline was seen after 4 weeks withdrawal. Pretreatment with a small dose of adrenaline inhibited the ulcerogenic action of a high dose of adrenaline. Pretreatment with reserpine, pyrogallol or iproniazid inhibited the action of adrenaline. It is concluded that adrenaline has a biphasic effect on gastric ulceration, the ulcerogenic action is due to its alpha-action and antiulcerogenic effect is due to development of tachyphylaxis."}
{"id": "PMID:279", "title": "[Comparison of drug effects on the isolated rat colon and duodenum].", "content": "Adrenaline and isoproterenol elicited nearly maximal relaxation of the colon even in small doses, whereas increase in the doses caused greater relaxation in the duodenum. In the colon, these drugs prevented, to a great extent the contraction induced by acetylcholine (ACh) and serotonin but in the duodenum were totally ineffective. Dibenamine and propranolol reduced adrenaline- and isoproterenol-induced relaxation in the duodenum, though propranolol decreased the relaxation caused by isoproterenol. Atropine prevented ACh-induced contraction in both the colon and duodenum in the same way. After 2-bromolysergic acid diethylamide, duodenal contraction caused by ACh or serotonin decreased by over 70%; however, the contraction of the colon was not significantly inhibited. Methysergide had similar effects, but to a lesser degree. In calcium-free bathing fluid without addition of Na2EDTA, ACh and prostaglandin E1 elicited contraction in the colon, but not in the duodenum.", "contents": "[Comparison of drug effects on the isolated rat colon and duodenum]. Adrenaline and isoproterenol elicited nearly maximal relaxation of the colon even in small doses, whereas increase in the doses caused greater relaxation in the duodenum. In the colon, these drugs prevented, to a great extent the contraction induced by acetylcholine (ACh) and serotonin but in the duodenum were totally ineffective. Dibenamine and propranolol reduced adrenaline- and isoproterenol-induced relaxation in the duodenum, though propranolol decreased the relaxation caused by isoproterenol. Atropine prevented ACh-induced contraction in both the colon and duodenum in the same way. After 2-bromolysergic acid diethylamide, duodenal contraction caused by ACh or serotonin decreased by over 70%; however, the contraction of the colon was not significantly inhibited. Methysergide had similar effects, but to a lesser degree. In calcium-free bathing fluid without addition of Na2EDTA, ACh and prostaglandin E1 elicited contraction in the colon, but not in the duodenum."}
{"id": "PMID:280", "title": "[Monoamine oxidase (XXXVI). Characteristics of benzylamine oxidase in the dog serum].", "content": "Enzymic properties of monoamine oxidase (MAO) in dog serum were studied and the following results were obtained. Some of enzymic properties of MAO in dog serum differed from that of mitochondrial MAO. When dog serum was fractionated by ammonium sulfate, proteins were concentrated in two fractions, such as 25 approximately 33% and 67 approximately 80% of saturated ammonium sulfate fraction, while MAO activity was concentrated in 40 approximately 50% of saturated ammonium sulfate fraction. The reaction rate of MAO in dog serum was found to be proportional to enzyme concentration. The optimum pH of MAO in dog serum was 7.0 which differed from that of MAO in rabbit serum (pH 8.0). Tris-HCl buffer strongly inhibited MAO activity in dog serum. When benzylamine was used as substrate, the highest activity was obtained compared with the other substrate used. The activities with butylamine, amylamine, beta-phenylethylamine and tyramine showed about 30% while tryptamine and serotonin showed 3 approximately 10% compared to that with benzymlamine as substrate. The value of pI50 of catron was about 3 X 10(-6) M and that of harmaline was about 3 X 10(-5) M, but pargyline did not inhibit MAO activity in dog serum at the concentration of 1 X 10(-4) M.", "contents": "[Monoamine oxidase (XXXVI). Characteristics of benzylamine oxidase in the dog serum]. Enzymic properties of monoamine oxidase (MAO) in dog serum were studied and the following results were obtained. Some of enzymic properties of MAO in dog serum differed from that of mitochondrial MAO. When dog serum was fractionated by ammonium sulfate, proteins were concentrated in two fractions, such as 25 approximately 33% and 67 approximately 80% of saturated ammonium sulfate fraction, while MAO activity was concentrated in 40 approximately 50% of saturated ammonium sulfate fraction. The reaction rate of MAO in dog serum was found to be proportional to enzyme concentration. The optimum pH of MAO in dog serum was 7.0 which differed from that of MAO in rabbit serum (pH 8.0). Tris-HCl buffer strongly inhibited MAO activity in dog serum. When benzylamine was used as substrate, the highest activity was obtained compared with the other substrate used. The activities with butylamine, amylamine, beta-phenylethylamine and tyramine showed about 30% while tryptamine and serotonin showed 3 approximately 10% compared to that with benzymlamine as substrate. The value of pI50 of catron was about 3 X 10(-6) M and that of harmaline was about 3 X 10(-5) M, but pargyline did not inhibit MAO activity in dog serum at the concentration of 1 X 10(-4) M."}
{"id": "PMID:281", "title": "[Combined use of bucolome and pyrazolone derivatives (1). Pharmacological activities and blood concentration].", "content": "A combination of two or more drugs may exert a drug-drug interaction, in which case the effect can be potentiated or antagonized. Such synergistic effects are well known in the case of pyrabital (barbital + aminopyrine) or irgapyrine (phenylbutazone + aminopyrine). Bucolome (BCP), a non-steroidal anti-inflammatory agent, has the chemical structure of a barbiturate and also resembles the formula of pheylbutazone. Thus the influence of BCP combination on the pharmacological activities of various pyrazolone derivatives was examined. BCP potentiated the analgesic and antipyretic effects of 4-aminoantipyrine (4A), methylaminoantipyrine (MA), aminopyrine (AM) and isopropylaminoantipyrine (IPA), which were substituted by the alkylamino group at 4-position of the pyrazolone ring. This potentiation occurred when the dose of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP and pyrazolone was 2:1 mola. The analgesic effects of antipyrine (AN), isopropylantipyrine (IP) and aminopropylone (AP), which were substituted by alkyl group or aminoacylamino group at 4-position, were not potentiated by BCP in any combination ratio. Most pyrazolones showed additive acute toxicity in their combination with BCP, but acute toxicities of 4A and AM, which were potentiated in analgesic effects, were decreased and antagonized when combined with BCP. The plasma concentration of AM was increased and prolonged by BCP, while that of IP remained much the same. These results suggest that the pharmacological activities are associated with certain molecular interactions between BCP and pyrazolones, which are substituted by the alkylamino group at 4-position of the pyrazolone ring.", "contents": "[Combined use of bucolome and pyrazolone derivatives (1). Pharmacological activities and blood concentration]. A combination of two or more drugs may exert a drug-drug interaction, in which case the effect can be potentiated or antagonized. Such synergistic effects are well known in the case of pyrabital (barbital + aminopyrine) or irgapyrine (phenylbutazone + aminopyrine). Bucolome (BCP), a non-steroidal anti-inflammatory agent, has the chemical structure of a barbiturate and also resembles the formula of pheylbutazone. Thus the influence of BCP combination on the pharmacological activities of various pyrazolone derivatives was examined. BCP potentiated the analgesic and antipyretic effects of 4-aminoantipyrine (4A), methylaminoantipyrine (MA), aminopyrine (AM) and isopropylaminoantipyrine (IPA), which were substituted by the alkylamino group at 4-position of the pyrazolone ring. This potentiation occurred when the dose of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP exceeded that of the pyrazolones, and was especially marked when combination ratio of BCP and pyrazolone was 2:1 mola. The analgesic effects of antipyrine (AN), isopropylantipyrine (IP) and aminopropylone (AP), which were substituted by alkyl group or aminoacylamino group at 4-position, were not potentiated by BCP in any combination ratio. Most pyrazolones showed additive acute toxicity in their combination with BCP, but acute toxicities of 4A and AM, which were potentiated in analgesic effects, were decreased and antagonized when combined with BCP. The plasma concentration of AM was increased and prolonged by BCP, while that of IP remained much the same. These results suggest that the pharmacological activities are associated with certain molecular interactions between BCP and pyrazolones, which are substituted by the alkylamino group at 4-position of the pyrazolone ring."}
{"id": "PMID:282", "title": "[Combined use of bucolome and pyrazolone derivatives (II). Complex formation due to interaction between bucolome and pyrazolones].", "content": "We have already reported that bucolome (BCP), a non-steroidal anti-inflammatory agent, potentiates significantly the analgesic and antipyretic effects of pyrazolones which are substituted by alkylamino group at 4-position of the pyrazolone ring. Physical and quantum chemistry were applied to the mechanism of this synergistic action. The solubility of BCP was markedly increased in proportion to elevation of aminopyrine (AM) concentration, but not by a combination with isopropylantipyrine (IP). The binding of BCP to bovine serum albumin was slightly inhibited by AM, but not by IP. The mixture of AM and BCP in aqueous media generated optical absorption in the ultraviolet differential spectrum, due to the charge transfer interaction. The results of the infrared or NMR spectrum demonstrated the formation of a hydrogen binding in non-aqueous media between BCP and AM. From the calculation of the charge on an atom, the energy of the highest occupied molecular orbital and the frontier electron density, BCP is considered to be a good electron acceptor. The beta-units of Mho of pyrazolones were found to correlate with the potentiation coefficient of analgesic activity in combination drugs. These results suggest that the complex formation between BCP and pyrazolones is an important factor for the synergism of action and is due to the charge transfer interaction and the hydrogen binding of both molecules.", "contents": "[Combined use of bucolome and pyrazolone derivatives (II). Complex formation due to interaction between bucolome and pyrazolones]. We have already reported that bucolome (BCP), a non-steroidal anti-inflammatory agent, potentiates significantly the analgesic and antipyretic effects of pyrazolones which are substituted by alkylamino group at 4-position of the pyrazolone ring. Physical and quantum chemistry were applied to the mechanism of this synergistic action. The solubility of BCP was markedly increased in proportion to elevation of aminopyrine (AM) concentration, but not by a combination with isopropylantipyrine (IP). The binding of BCP to bovine serum albumin was slightly inhibited by AM, but not by IP. The mixture of AM and BCP in aqueous media generated optical absorption in the ultraviolet differential spectrum, due to the charge transfer interaction. The results of the infrared or NMR spectrum demonstrated the formation of a hydrogen binding in non-aqueous media between BCP and AM. From the calculation of the charge on an atom, the energy of the highest occupied molecular orbital and the frontier electron density, BCP is considered to be a good electron acceptor. The beta-units of Mho of pyrazolones were found to correlate with the potentiation coefficient of analgesic activity in combination drugs. These results suggest that the complex formation between BCP and pyrazolones is an important factor for the synergism of action and is due to the charge transfer interaction and the hydrogen binding of both molecules."}
{"id": "PMID:283", "title": "Fructose 1,6-bisphosphate aldolase activity of Rhizobium species.", "content": "FDP aldolase was found to be present in the cell-free extracts of Rhizobium leguminosarum, Rhizobium phaseoli, Rhizobium trifolii, Rhizobium meliloti, Rhizobium lupini, Rhizobium japonicum and Rhizobium species from Arachis hypogaea and Sesbania cannabina. The enzyme in 3 representative species has optimal activity at pH 8.4 in 0.2M veronal buffer. The enzyme activity was completely lost by treatment at 60 degrees C for 15 min. The Km values were in the range from 2.38 to 4.55 X 10(-6)M FDP. Metal chelating agents inhibited enzyme activity, but monovalent or bivalent metal ions failed to stimulate the activity. Bivalent metal ions in general were rather inhibitory.", "contents": "Fructose 1,6-bisphosphate aldolase activity of Rhizobium species. FDP aldolase was found to be present in the cell-free extracts of Rhizobium leguminosarum, Rhizobium phaseoli, Rhizobium trifolii, Rhizobium meliloti, Rhizobium lupini, Rhizobium japonicum and Rhizobium species from Arachis hypogaea and Sesbania cannabina. The enzyme in 3 representative species has optimal activity at pH 8.4 in 0.2M veronal buffer. The enzyme activity was completely lost by treatment at 60 degrees C for 15 min. The Km values were in the range from 2.38 to 4.55 X 10(-6)M FDP. Metal chelating agents inhibited enzyme activity, but monovalent or bivalent metal ions failed to stimulate the activity. Bivalent metal ions in general were rather inhibitory."}
{"id": "PMID:284", "title": "Prevention of cell agglutination and competence in a genetically transformable strain of Pneumococcus by D-glucosamine and D-galactosamine.", "content": "In the presence of amino sugars D-glucosamine and D-galactosamine no spontaneous competence could be observed in the highly transformable R6bd strain of Pneumococcus or it was decreased by several orders of magnitude. The highest inhibition of competence was detected when the amino sugar at a concentration 5 mg/ml of the medium was added not only to the transformation but also to the pretransformation medium. After a 150 min growth in the transformation medium in the presence of the amino sugar a 3--4-fold greater number of cells (as a viable count) could be detected as compared with the control without the amino sugar. It was found microscopically that the amino sugar prevents natural agglutination, which normally occurs in the competent culture. The role of specific amino sugar determinants for binding of the competence factor on the cell surface and the resulting inhibitory effect of these sugars on the development of competence are discussed.", "contents": "Prevention of cell agglutination and competence in a genetically transformable strain of Pneumococcus by D-glucosamine and D-galactosamine. In the presence of amino sugars D-glucosamine and D-galactosamine no spontaneous competence could be observed in the highly transformable R6bd strain of Pneumococcus or it was decreased by several orders of magnitude. The highest inhibition of competence was detected when the amino sugar at a concentration 5 mg/ml of the medium was added not only to the transformation but also to the pretransformation medium. After a 150 min growth in the transformation medium in the presence of the amino sugar a 3--4-fold greater number of cells (as a viable count) could be detected as compared with the control without the amino sugar. It was found microscopically that the amino sugar prevents natural agglutination, which normally occurs in the competent culture. The role of specific amino sugar determinants for binding of the competence factor on the cell surface and the resulting inhibitory effect of these sugars on the development of competence are discussed."}
{"id": "PMID:285", "title": "Effect of some aldoses on growth of Saccharomyces cerevisiae inhibited with molybdenum.", "content": "The inhibitory effect of molybdenum ions on growth of yeasts at pH 5.5 was found to be decreased by aldoses in the following order: D-talose greater than L-mannose greater than L-ribose greater than D-lyxose greater than L-galactose greater than L-arabinose greater than L-glucose greater than L-xylose. Increased concentrations of molybdenum brought about morphological changes of yeast cells. Cells grown under these conditions were smaller, had thicker walls and formed clusters.", "contents": "Effect of some aldoses on growth of Saccharomyces cerevisiae inhibited with molybdenum. The inhibitory effect of molybdenum ions on growth of yeasts at pH 5.5 was found to be decreased by aldoses in the following order: D-talose greater than L-mannose greater than L-ribose greater than D-lyxose greater than L-galactose greater than L-arabinose greater than L-glucose greater than L-xylose. Increased concentrations of molybdenum brought about morphological changes of yeast cells. Cells grown under these conditions were smaller, had thicker walls and formed clusters."}
{"id": "PMID:286", "title": "Transport properties of membrane vesicles from Acholeplasma laidlawii. II. Kinetic characteristics and specificity of glucose transport system.", "content": "The glucose transport system of membrane vesicles isolated from Acholeplasma laidlawii is saturable, with a Km of 21.2 mum and V of 0.68 nmol min-1 (mg protein)-1. The process is pH-dependent and a break occurs in the Arrhenius plot at 15 degrees C. Exogenous substrates did not stimulate glucose transport probably due to their inability to penetrate into membrane vesicles. 3-O-Methylglucose and 6-deoxyglucose competitively inhibited glucose transport. Maltose inhibited transport of glucose noncompetitively. These sugars also elicited glucose efflux from preloaded membrane vesicles.", "contents": "Transport properties of membrane vesicles from Acholeplasma laidlawii. II. Kinetic characteristics and specificity of glucose transport system. The glucose transport system of membrane vesicles isolated from Acholeplasma laidlawii is saturable, with a Km of 21.2 mum and V of 0.68 nmol min-1 (mg protein)-1. The process is pH-dependent and a break occurs in the Arrhenius plot at 15 degrees C. Exogenous substrates did not stimulate glucose transport probably due to their inability to penetrate into membrane vesicles. 3-O-Methylglucose and 6-deoxyglucose competitively inhibited glucose transport. Maltose inhibited transport of glucose noncompetitively. These sugars also elicited glucose efflux from preloaded membrane vesicles."}
{"id": "PMID:287", "title": "Transport of 4-deoxy- and 6-deoxy-D-glucose in baker's yeast.", "content": "Tritium-labelled 4-deoxy-D-glucose (4-dglc) and 6-deoxy-D-glucose (6-dgcl) were prepared by catalytic hydrogenolysis of the corresponding deoxyiodo derivatives with gaseous tritium. The two sugars are transported into Saccharomyces cerevisiae by both the constitutive glucose and the inducible galactose carrier. Uranyl ions are powerful inhibitors. The pH optimum in uninduced cells lies at 5.5 for both sugars, the apparent activation energies (between 15 and 35 degrees C) are 25.1 kJ/mol and 16.5 kJ/mol, respectively. The steady-state intracellular concentration of both sugars is less than the extracellular one (no uphill transport). Neither of them is a substrate of yeast hexokinase. 4-Deoxy-D-glucose undergoes a dinitrophenol-sensitive conversion to an unknown metabolite which is not phosphorylated and may represent one of its oxidation products.", "contents": "Transport of 4-deoxy- and 6-deoxy-D-glucose in baker's yeast. Tritium-labelled 4-deoxy-D-glucose (4-dglc) and 6-deoxy-D-glucose (6-dgcl) were prepared by catalytic hydrogenolysis of the corresponding deoxyiodo derivatives with gaseous tritium. The two sugars are transported into Saccharomyces cerevisiae by both the constitutive glucose and the inducible galactose carrier. Uranyl ions are powerful inhibitors. The pH optimum in uninduced cells lies at 5.5 for both sugars, the apparent activation energies (between 15 and 35 degrees C) are 25.1 kJ/mol and 16.5 kJ/mol, respectively. The steady-state intracellular concentration of both sugars is less than the extracellular one (no uphill transport). Neither of them is a substrate of yeast hexokinase. 4-Deoxy-D-glucose undergoes a dinitrophenol-sensitive conversion to an unknown metabolite which is not phosphorylated and may represent one of its oxidation products."}
{"id": "PMID:288", "title": "Gluconic acid production by Penicillium puberulum.", "content": "Twenty-five Penicillium species isolated from Egyptian soil were examined for their ability to produce gluconic acid in surface culture. Of the eight species capable of producing gluconic acid, Penicillium puberulum gave the maximum yield (91% gluconic acid from glucose after 7 days of fermentation with 3% CaCO3). Peptone was the best nitrogen source for acid fermentation and glucose was superior to sucrose. Addition of low concentrations of KH2PO4 and MgSO4 - 7 H2O stimulated acid production. An initial pH of 6.1 was most favourable for acid accumulation and addition of CaCO3 was necessary for maximum acid production.", "contents": "Gluconic acid production by Penicillium puberulum. Twenty-five Penicillium species isolated from Egyptian soil were examined for their ability to produce gluconic acid in surface culture. Of the eight species capable of producing gluconic acid, Penicillium puberulum gave the maximum yield (91% gluconic acid from glucose after 7 days of fermentation with 3% CaCO3). Peptone was the best nitrogen source for acid fermentation and glucose was superior to sucrose. Addition of low concentrations of KH2PO4 and MgSO4 - 7 H2O stimulated acid production. An initial pH of 6.1 was most favourable for acid accumulation and addition of CaCO3 was necessary for maximum acid production."}
{"id": "PMID:289", "title": "A simple method of isolation and purification of cultures of wood-rotting fungi.", "content": "A simple method of isolation and purification of cultures of higher fungi, mainly wood-rotting fungi, without special requirements for the presence of nitrogencontaining nutrients is described. Parts of fruiting bodies, spores or infected wood is inoculated on Petri dishes with an agar medium of the following composition: 1.0 g KH2PO4, 0.2 g MgSO4 - 7 H2O, 0.1 g caSO4, 0.01 g Fe2(SO4)3, 10.0 g glucose, tap water to 1 litre; 20.0 g agar. This medium does not suit most of the contaminants but fungal hyphae overgrow the whole surface of the dish so that a purified culture can be obtained from parts distant from the inoculation site.", "contents": "A simple method of isolation and purification of cultures of wood-rotting fungi. A simple method of isolation and purification of cultures of higher fungi, mainly wood-rotting fungi, without special requirements for the presence of nitrogencontaining nutrients is described. Parts of fruiting bodies, spores or infected wood is inoculated on Petri dishes with an agar medium of the following composition: 1.0 g KH2PO4, 0.2 g MgSO4 - 7 H2O, 0.1 g caSO4, 0.01 g Fe2(SO4)3, 10.0 g glucose, tap water to 1 litre; 20.0 g agar. This medium does not suit most of the contaminants but fungal hyphae overgrow the whole surface of the dish so that a purified culture can be obtained from parts distant from the inoculation site."}
{"id": "PMID:292", "title": "[Studies on low volume priming heart lung bypass (author's transl)].", "content": "This report concerns the feasibility of low volume priming extracorporeal circulation. Through this study, the bubble oxygenator with Zuhdi's heat exchange was used. Moderate hypothermia with surface cooling and hemodilution perfusion with 5 per cent D/W was evaluated in 32 mongrel dogs and 16 clinical open heart cases. The results obtained here were as follow: 1) Body temperature reduction by surface cooling before bypass provided more even cooling than did core cooling by low flow partial bypass alone. 2) In regard to cardiac loading on returning the whole perfusate of the circuit to patient, approximately 20 ml/kg of 5 per cent D/W was feasible as a priming solution. 3) To reduce the blood visicosity, hemodilution technique with 5 per cent D/W was superior, and hemodilution effect during postoperative periods was temporaly. 4) The excess lactate volume postulated by Huckabee was a available index to evaluate metabolic acidosis during the extracorporeal circulation. 5) With aid of surface cooling, the acid-base balance during perfusion was kept to lesser extent than that of core cooling only. 6) This study indicated that the low priming perfusion in conjunction with surface cooling hypothermia was a reliable technique for the open heart operation and may be applied in more prolonged perfusion.", "contents": "[Studies on low volume priming heart lung bypass (author's transl)]. This report concerns the feasibility of low volume priming extracorporeal circulation. Through this study, the bubble oxygenator with Zuhdi's heat exchange was used. Moderate hypothermia with surface cooling and hemodilution perfusion with 5 per cent D/W was evaluated in 32 mongrel dogs and 16 clinical open heart cases. The results obtained here were as follow: 1) Body temperature reduction by surface cooling before bypass provided more even cooling than did core cooling by low flow partial bypass alone. 2) In regard to cardiac loading on returning the whole perfusate of the circuit to patient, approximately 20 ml/kg of 5 per cent D/W was feasible as a priming solution. 3) To reduce the blood visicosity, hemodilution technique with 5 per cent D/W was superior, and hemodilution effect during postoperative periods was temporaly. 4) The excess lactate volume postulated by Huckabee was a available index to evaluate metabolic acidosis during the extracorporeal circulation. 5) With aid of surface cooling, the acid-base balance during perfusion was kept to lesser extent than that of core cooling only. 6) This study indicated that the low priming perfusion in conjunction with surface cooling hypothermia was a reliable technique for the open heart operation and may be applied in more prolonged perfusion."}
{"id": "PMID:293", "title": "[Studies on extracorporeal circulation with large volume hemodilution using lactate ringer's solution and low molecular weight dextran: alterations of acid-base balance associated with intentional hemodilution (author's transl)].", "content": "Twenty mongrel dogs, weighing between 7.5 and 13.0 kg were used to investigate the percentage limits permissible for hemodilution using a double-helical reservoir heart-lung machine which has a 1,100 ml of priming volume. In both 40 and 50 per cent groups of intentional hemodilution by 30 minute extracorporeal circulation, remarkable anemia was inevitable and recovery was extremely slow, especially in the 50 per cent dilution group. In both 40 and 50 per cent groups of intentional hemodilutions by 30 minute extracorporeal circulation, metabolic acidosis was observed. In 50 per cent group of intentional hemodilution, no improvement of metabolic acidosis was observed even after perfusion. When sodium bicarbonate was administered to 40 per cent hemodilution group, minimum alterations of acid-base balance and of serum electrolytes were observed during and after extracorporeal perfusion. When sodium bicarbonate was administered to 50 per cent hemodilution group, metabolic acidosis was more evident than in 40 per cent hemodilution group accompanied with an increase in serum sodium concentration and a decrease in serum chloride concentration. These data qualify the use of 40 per cent intentional hemodilution using Lactate Ringer's solution or low molecular weight dextran for 30 minute extracorporeal circulation when sodium bicarbonate is administered in adequate amounts.", "contents": "[Studies on extracorporeal circulation with large volume hemodilution using lactate ringer's solution and low molecular weight dextran: alterations of acid-base balance associated with intentional hemodilution (author's transl)]. Twenty mongrel dogs, weighing between 7.5 and 13.0 kg were used to investigate the percentage limits permissible for hemodilution using a double-helical reservoir heart-lung machine which has a 1,100 ml of priming volume. In both 40 and 50 per cent groups of intentional hemodilution by 30 minute extracorporeal circulation, remarkable anemia was inevitable and recovery was extremely slow, especially in the 50 per cent dilution group. In both 40 and 50 per cent groups of intentional hemodilutions by 30 minute extracorporeal circulation, metabolic acidosis was observed. In 50 per cent group of intentional hemodilution, no improvement of metabolic acidosis was observed even after perfusion. When sodium bicarbonate was administered to 40 per cent hemodilution group, minimum alterations of acid-base balance and of serum electrolytes were observed during and after extracorporeal perfusion. When sodium bicarbonate was administered to 50 per cent hemodilution group, metabolic acidosis was more evident than in 40 per cent hemodilution group accompanied with an increase in serum sodium concentration and a decrease in serum chloride concentration. These data qualify the use of 40 per cent intentional hemodilution using Lactate Ringer's solution or low molecular weight dextran for 30 minute extracorporeal circulation when sodium bicarbonate is administered in adequate amounts."}
{"id": "PMID:295", "title": "Purification and characterization of phosphodiesterase from Crotalus venom.", "content": "A procedure for the purification of phosphodiesterase from Crotalus venom on DEAE-cellulose at alkaline pH is described. The enzyme gives a single band in polyacrylamide gels and is free of contaminating nucleolytic enzymes. The molecular weight is about 115000. Concentration in an Amicon ultrafiltrator gave a highly concentrated active enzyme. Phosphodiesterase is relatively stable and can be stored at 4 degrees C in the presence of Mg2 and serum albumin for years. For the detection of contaminating endonuclease, an assay was used in which tRNA was the substrate and possible internal breaks were detected in polyacrylamide gel after denaturation. With bis(p-nitrophenyl) phosphate as substrate, 15mM Mg2 was necessary for optimal activity. The reaction remained linear for at least 15 min at 22 degrees C. At 45 degrees C, the liberation of p-nitrophenol was highest within 25 min of incubation. At 75 degrees C, inactivation of the enzyme occurred after 4 min.", "contents": "Purification and characterization of phosphodiesterase from Crotalus venom. A procedure for the purification of phosphodiesterase from Crotalus venom on DEAE-cellulose at alkaline pH is described. The enzyme gives a single band in polyacrylamide gels and is free of contaminating nucleolytic enzymes. The molecular weight is about 115000. Concentration in an Amicon ultrafiltrator gave a highly concentrated active enzyme. Phosphodiesterase is relatively stable and can be stored at 4 degrees C in the presence of Mg2 and serum albumin for years. For the detection of contaminating endonuclease, an assay was used in which tRNA was the substrate and possible internal breaks were detected in polyacrylamide gel after denaturation. With bis(p-nitrophenyl) phosphate as substrate, 15mM Mg2 was necessary for optimal activity. The reaction remained linear for at least 15 min at 22 degrees C. At 45 degrees C, the liberation of p-nitrophenol was highest within 25 min of incubation. At 75 degrees C, inactivation of the enzyme occurred after 4 min."}
{"id": "PMID:296", "title": "Limited hydrolysis of tRNA by phosphodiesterase.", "content": "Digestion of tRNA by electrophoretically pure phosphodiesterase is limited to a short sequence of nucleotides at the 3'-terminus. On the average, four percent of all nucleotides can be released from tRNA. The optimum Mg2 concentration is 10mM and the optimum pH 9.2. The mode of action is a random attack by the enzyme on the substrate. The terminal AMP is completely removed at 15 degrees C after short incubation; about 400 mol of AMP were removed per min by 1 mol of enzyme. The following CMP residues are released much more slowly; at 15 degrees C incompletely, and at 37 degrees C more or less completely in 1 h. In about 50% of the tRNA molecules, the fourth nucleotide could be removed in very long incubations or with very high enzyme concentrations.", "contents": "Limited hydrolysis of tRNA by phosphodiesterase. Digestion of tRNA by electrophoretically pure phosphodiesterase is limited to a short sequence of nucleotides at the 3'-terminus. On the average, four percent of all nucleotides can be released from tRNA. The optimum Mg2 concentration is 10mM and the optimum pH 9.2. The mode of action is a random attack by the enzyme on the substrate. The terminal AMP is completely removed at 15 degrees C after short incubation; about 400 mol of AMP were removed per min by 1 mol of enzyme. The following CMP residues are released much more slowly; at 15 degrees C incompletely, and at 37 degrees C more or less completely in 1 h. In about 50% of the tRNA molecules, the fourth nucleotide could be removed in very long incubations or with very high enzyme concentrations."}
{"id": "PMID:297", "title": "Ecdysone Oxidase, an enzyme from the blowfly Calliphora erythrocephala (Meigen).", "content": "In the blowfly, the formation of 3-dehydroecdysone from the insect molting hormone ecdysone is catalyzed by an enzyme which carries hydrogen from ecdysone and ecdysterone to oxygen. The enzyme is therefore called \"ecdysone oxidase\". Two methods are described for the detection of ecdysone oxidase activity, one using a radiolabelled substrate which is separated from the product by thin-layer chromatography after the reaction, and the other using dichloroindophenol, which is discoloured by the redox reaction. The ecdysone oxidase is purified by a factor of 2200 from prepupae of Calliphora erythrocephala using salt precipitation and ion exchange chromatography. The ecdysone oxidase has a Km value for ecdysone of 42muM. The pH optimum is 6.5. The temperature optimum lies at 45 degrees C. The ecdysone oxidase has a molecular weight of 240000.", "contents": "Ecdysone Oxidase, an enzyme from the blowfly Calliphora erythrocephala (Meigen). In the blowfly, the formation of 3-dehydroecdysone from the insect molting hormone ecdysone is catalyzed by an enzyme which carries hydrogen from ecdysone and ecdysterone to oxygen. The enzyme is therefore called \"ecdysone oxidase\". Two methods are described for the detection of ecdysone oxidase activity, one using a radiolabelled substrate which is separated from the product by thin-layer chromatography after the reaction, and the other using dichloroindophenol, which is discoloured by the redox reaction. The ecdysone oxidase is purified by a factor of 2200 from prepupae of Calliphora erythrocephala using salt precipitation and ion exchange chromatography. The ecdysone oxidase has a Km value for ecdysone of 42muM. The pH optimum is 6.5. The temperature optimum lies at 45 degrees C. The ecdysone oxidase has a molecular weight of 240000."}
{"id": "PMID:298", "title": "Using a hospital for desensitization of an outpatient's illness-related fears.", "content": "An outpatient with phobias related to enclosed places, hospitals, doctors, and cancer was treated by systematic desensitization; the facilities of a general hospital were used for part of the process. Steps in treatment included securing a complete psychiatric and social history, teaching the patient relaxation therapy techniques, and establishing a hierarchy of anxiety-provoking stimuli specifically related to the patient's fears. After desensitization the patient was able to enter the hospital for tests for a physical ailment and showed a general decrease in her fears.", "contents": "Using a hospital for desensitization of an outpatient's illness-related fears. An outpatient with phobias related to enclosed places, hospitals, doctors, and cancer was treated by systematic desensitization; the facilities of a general hospital were used for part of the process. Steps in treatment included securing a complete psychiatric and social history, teaching the patient relaxation therapy techniques, and establishing a hierarchy of anxiety-provoking stimuli specifically related to the patient's fears. After desensitization the patient was able to enter the hospital for tests for a physical ailment and showed a general decrease in her fears."}
{"id": "PMID:325", "title": "Analysis of immunosuppression generated by the graft-versus-host reaction. I. A suppressor T-cell component studied in vivo.", "content": "The kinetics and cellular characteristics of immunosuppression in (CBA-p X C57/Bl)F1 mice during graft-versus-host (GVH) reaction induced with spleen cells from either parental strain have been investigated. Effects on PFC responses to thymus-dependent (chicken red blood cells) and independent (levan) antigens have been compared. The unresponsive state which developed in GVH mice was expressed to comparable extent by their spleen cells following transfer to irradiated recipients. Furthermore, GVH spleen cells suppressed normal spleen cells in a mixed transfer system, but this effect was lost completely by day 21 whereas the original donors (or their cells) were still totally refractory after 80 days. This active suppressor effect was found to be mediated by T cells of perental origin based on cell fractionation analysis and selective deletion of donor or host cells by alloimmune attack. The delayed transfer of GVH cells to irradiated repopulated recipients challenged with antigen, indicated that suppressor T cells exert an anti-mitotic influence on antigen-stimulated B-cell proliferation. Supplementation of macrophage-depleted, anti-theta-treated GVH spleen cells with purified normal T cells demonstrated that B cells in GVH mice are normally reactive even when active suppression by T cells is no longer demonstrable. The likelihood that this later phase of immunosuppression is attributable to another mechanism is discussed.", "contents": "Analysis of immunosuppression generated by the graft-versus-host reaction. I. A suppressor T-cell component studied in vivo. The kinetics and cellular characteristics of immunosuppression in (CBA-p X C57/Bl)F1 mice during graft-versus-host (GVH) reaction induced with spleen cells from either parental strain have been investigated. Effects on PFC responses to thymus-dependent (chicken red blood cells) and independent (levan) antigens have been compared. The unresponsive state which developed in GVH mice was expressed to comparable extent by their spleen cells following transfer to irradiated recipients. Furthermore, GVH spleen cells suppressed normal spleen cells in a mixed transfer system, but this effect was lost completely by day 21 whereas the original donors (or their cells) were still totally refractory after 80 days. This active suppressor effect was found to be mediated by T cells of perental origin based on cell fractionation analysis and selective deletion of donor or host cells by alloimmune attack. The delayed transfer of GVH cells to irradiated repopulated recipients challenged with antigen, indicated that suppressor T cells exert an anti-mitotic influence on antigen-stimulated B-cell proliferation. Supplementation of macrophage-depleted, anti-theta-treated GVH spleen cells with purified normal T cells demonstrated that B cells in GVH mice are normally reactive even when active suppression by T cells is no longer demonstrable. The likelihood that this later phase of immunosuppression is attributable to another mechanism is discussed."}
{"id": "PMID:329", "title": "Pneumococcal type-associated variability in alternate complement pathway activation.", "content": "Opsonization of Streptococcus pneumoniae may be mediated by the alternate complement pathway. To study the importance of this interaction to human disease, complement consumption by pneumococci of various serotypes was measured in humwn serum chelated with ethyleneglycoltraacetic acid, a substance that blocks the classic but not the alternate complement pathwway. Serotype I, in contrast to all other types studied, lacked ability to consume complement in this system. The ability for serotypes III, IV, and VIII to activate the alternate pathway could be eliminated by prior serum absorption at O C with they type in question, a condition that would remove antibody but not complement. Types VII, XII, XIV, and XXV readily activated the alternate pathway in unabsorbed and absorbed sera. Differences could not be related to properties of the capsules. It was concluded that types I, III, IV, and VIII lack intrinsic ability to activate and thus be opsonized by the alternate complement pathway, although types III, IV, and VIII can do so in concert with specific antibody. The fact that these same types are especially prominent in human disease suggests that the ability to evade opsonization by the alternate complement pathway in pre-antibody phases of infection may be a virulence factor in pneumococci.", "contents": "Pneumococcal type-associated variability in alternate complement pathway activation. Opsonization of Streptococcus pneumoniae may be mediated by the alternate complement pathway. To study the importance of this interaction to human disease, complement consumption by pneumococci of various serotypes was measured in humwn serum chelated with ethyleneglycoltraacetic acid, a substance that blocks the classic but not the alternate complement pathwway. Serotype I, in contrast to all other types studied, lacked ability to consume complement in this system. The ability for serotypes III, IV, and VIII to activate the alternate pathway could be eliminated by prior serum absorption at O C with they type in question, a condition that would remove antibody but not complement. Types VII, XII, XIV, and XXV readily activated the alternate pathway in unabsorbed and absorbed sera. Differences could not be related to properties of the capsules. It was concluded that types I, III, IV, and VIII lack intrinsic ability to activate and thus be opsonized by the alternate complement pathway, although types III, IV, and VIII can do so in concert with specific antibody. The fact that these same types are especially prominent in human disease suggests that the ability to evade opsonization by the alternate complement pathway in pre-antibody phases of infection may be a virulence factor in pneumococci."}
{"id": "PMID:330", "title": "Conditions for production, and some characteristics, of mycobacterial growth inhibitory factor produced by spleen cells from mice immunized with viable cells of the attenuated H37Ra strain of Mycobacterium tuberculosis.", "content": "Mycobacterial growth inhibitory factor (MycoIF), found in supernatant fluids of mouse spleen cell cultures that have been stimulated in vitro with homologous  antigen, inhibited the intracellular multiplication of virulent tubercle bacilli within normal mouse peritoneal macrophages in vitro. Antigenically stimulated H37Ra-immunized mouse spleen cells required 72 h of incubation to produce supernatant fluids that would cause intracellular inhibition. Supernatant fluids from 48-h mouse spleen cell cultures were not able to produce intracellular inhibition. Investigation of the culture conditions showed that at lease 1.0% human serum was required in the tissue culture medium for the production of MycoIF by spleen cells from immunized mice. MycoIF activity was noted only in supernatant fluids from spleen cell cultures incubated with antigen for 72 h. MycoIF was nondialyzable and unaffected by freezing, lyophilization, or incubation at 60 C for 30 min. However, MycoIF was inactivated after incubation at 80 C for 30 min. MycoIF was unaffected by low hydrogen ion concentrations (pH 7 to 12), but exposure to higher hydrogen ion concentrations (pH 6, pH 5) significantly decrease MycoIF activity, and exposure to pH 4 to 2 abolished all activity. Supernatant fluids diluted 1:32 were still able to produce significant intracellular inhibition of growth of virulent tubercle bacilli.", "contents": "Conditions for production, and some characteristics, of mycobacterial growth inhibitory factor produced by spleen cells from mice immunized with viable cells of the attenuated H37Ra strain of Mycobacterium tuberculosis. Mycobacterial growth inhibitory factor (MycoIF), found in supernatant fluids of mouse spleen cell cultures that have been stimulated in vitro with homologous  antigen, inhibited the intracellular multiplication of virulent tubercle bacilli within normal mouse peritoneal macrophages in vitro. Antigenically stimulated H37Ra-immunized mouse spleen cells required 72 h of incubation to produce supernatant fluids that would cause intracellular inhibition. Supernatant fluids from 48-h mouse spleen cell cultures were not able to produce intracellular inhibition. Investigation of the culture conditions showed that at lease 1.0% human serum was required in the tissue culture medium for the production of MycoIF by spleen cells from immunized mice. MycoIF activity was noted only in supernatant fluids from spleen cell cultures incubated with antigen for 72 h. MycoIF was nondialyzable and unaffected by freezing, lyophilization, or incubation at 60 C for 30 min. However, MycoIF was inactivated after incubation at 80 C for 30 min. MycoIF was unaffected by low hydrogen ion concentrations (pH 7 to 12), but exposure to higher hydrogen ion concentrations (pH 6, pH 5) significantly decrease MycoIF activity, and exposure to pH 4 to 2 abolished all activity. Supernatant fluids diluted 1:32 were still able to produce significant intracellular inhibition of growth of virulent tubercle bacilli."}
{"id": "PMID:331", "title": "Effect of pneumococci on blood clotting, platelets, and polymorphonuclear leukocytes.", "content": "Infections due to Streptococcus pneumoniae and products from the organism have been associated with alterations in blood clotting and function of platelets. Pneumococci and pneumococcal polysaccharide shortened the clotting times of whole blood, platelet-rich plasma (PRP), and platelet-poor plasma (PPP) in vitro. Clotting times of PPP and PRP from C6-deficient animals were likewise decreased. The bacteria had no effect on the  one-stage prothrombin time or the partial thromboplastin time when the organisms were used as activating agents. Platelets aggregated in the presence of pneumococci,  but aggregation was prevented by the addition of cyclic adenosine 3', 5'-monophosphate (cAMP). Furthermore, cAMP corrected the shortened clotting time of PRP in the presence of pneumococci. The clumping and release of polymorphonuclear coagulant that was induced by pneumococci was not prevented by cAMP. Thus, pneumococci exert several dose-dependent thromboplastic effects: (i) release of platelet thromboplastic substances; (ii) a direct thromboplastic effect; and (iii) release of polymorphonuclear coagulant.", "contents": "Effect of pneumococci on blood clotting, platelets, and polymorphonuclear leukocytes. Infections due to Streptococcus pneumoniae and products from the organism have been associated with alterations in blood clotting and function of platelets. Pneumococci and pneumococcal polysaccharide shortened the clotting times of whole blood, platelet-rich plasma (PRP), and platelet-poor plasma (PPP) in vitro. Clotting times of PPP and PRP from C6-deficient animals were likewise decreased. The bacteria had no effect on the  one-stage prothrombin time or the partial thromboplastin time when the organisms were used as activating agents. Platelets aggregated in the presence of pneumococci,  but aggregation was prevented by the addition of cyclic adenosine 3', 5'-monophosphate (cAMP). Furthermore, cAMP corrected the shortened clotting time of PRP in the presence of pneumococci. The clumping and release of polymorphonuclear coagulant that was induced by pneumococci was not prevented by cAMP. Thus, pneumococci exert several dose-dependent thromboplastic effects: (i) release of platelet thromboplastic substances; (ii) a direct thromboplastic effect; and (iii) release of polymorphonuclear coagulant."}
{"id": "PMID:332", "title": "Some properties of a D-alanine carboxypeptidase in envelope fractions of Neisseria gonorrhoeae.", "content": "Envelope preparations of Neisseria gonorrhoeae strain GC1 (a stable, piliated strain of intermediate colony morphology) and type T1 possess a D-alanine carboxypeptidase which releases the terminal alanine residue from the uridine 5'-diphosphate-N-acetyl muramylpentapeptide substrate (isolated from Bacillus cereus T). The D-alanine carboxypeptidase of the GC1 envelopes has a broad pH optimum between pH 8.0 to 10.0. When the molarity of the tris(hydroxymethyl)aminomethane buffer was varied, the activity showed an optimum over the range 0.2 to 0.4 M. Activity was higher (135% of control level) when 20 to 80 mM Mg2+ was present. The Km for the enzyme was 0.25 mM. The D-alanine carboxypeptidase was inhibited by several beta-lactam antibiotics and the 50% inhibitory levels were 10(-8) M penicillin G, 10(-8) M ampicillin, 10(-5) M cloxacillin, and 5 x 10(-7) M methicillin.", "contents": "Some properties of a D-alanine carboxypeptidase in envelope fractions of Neisseria gonorrhoeae. Envelope preparations of Neisseria gonorrhoeae strain GC1 (a stable, piliated strain of intermediate colony morphology) and type T1 possess a D-alanine carboxypeptidase which releases the terminal alanine residue from the uridine 5'-diphosphate-N-acetyl muramylpentapeptide substrate (isolated from Bacillus cereus T). The D-alanine carboxypeptidase of the GC1 envelopes has a broad pH optimum between pH 8.0 to 10.0. When the molarity of the tris(hydroxymethyl)aminomethane buffer was varied, the activity showed an optimum over the range 0.2 to 0.4 M. Activity was higher (135% of control level) when 20 to 80 mM Mg2+ was present. The Km for the enzyme was 0.25 mM. The D-alanine carboxypeptidase was inhibited by several beta-lactam antibiotics and the 50% inhibitory levels were 10(-8) M penicillin G, 10(-8) M ampicillin, 10(-5) M cloxacillin, and 5 x 10(-7) M methicillin."}
{"id": "PMID:334", "title": "Host defense against the pneumococcus in T-lymphocyte-deficient, nude mice.", "content": "Resistance to pneumococcal infection was tested in T-lymphocyte-deficient, nude (nu/nu) mice. Pneumococcal serum opsonizing activity, in vivo phagocytosis of the pneumococcus, and the mean lethal dose for the pneumococcus were all found to be the same in nude mice as in control (+/+) mice. T-lymphocytes do not appear to play a significant role in the host's defense against the pneumococcus.", "contents": "Host defense against the pneumococcus in T-lymphocyte-deficient, nude mice. Resistance to pneumococcal infection was tested in T-lymphocyte-deficient, nude (nu/nu) mice. Pneumococcal serum opsonizing activity, in vivo phagocytosis of the pneumococcus, and the mean lethal dose for the pneumococcus were all found to be the same in nude mice as in control (+/+) mice. T-lymphocytes do not appear to play a significant role in the host's defense against the pneumococcus."}
{"id": "PMID:333", "title": "Phenomenon of hot-cold hemolysis: chelator-induced lysis of sphingomyelinase-treated erythrocytes.", "content": "Staphylococcus aureus produces a phospholipase C specific for sphingomyelin (beta-hemolysin). Erythrocytes with approximately 50% sphingomyelin in their membranes, e.g., from sheep, have been shown to have up to 60% of this phospholipid hydrolyzed by this enzyme at 37 C in isotonic buffered saline without hemolysis. Cooling of sphingomyelinase C-treated erythrocytes to 4 C causes complete lysis of the cells, a phenomenon known as hot-cold hemolysis. The addition of ethylenediaminetetraacetate (EDTA) to sheep erythrocytes preincubated with sphingomyelinase C was found to induce rapid hemolysis at 37 C. The treated cells became susceptible to chelator-induced hemolysis and to hot-cold hemolysis simultaneously, and the degree of lysis of both mechanisms increased equally with prolonged preincubation with sphingomyelinase C. Erythrocytes of species not readily susceptible to hot-cold hemolysis were equally insusceptible to chelator-induced lysis. Chelators of the EDTA series were the most effective, whereas chelators more specific for Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+ were without effect. The rate of chelator-induced lysis was dependent on the preincubation period with beta-hemolysin and on the concentration of chelator added. The optimal concentration of EDTA was found to equal the amount of exogenously added Mg2+, a cation necessary for sphingomyelinase C activity. Hypotonicity increased the rate of chelator-induced hemolysis, whereas increasing the osmotic pressure to twice isotonic completely inhibited chelator-induced lysis. The data suggest that exogenously added and/or membrane-bound divalent cations are important for the stability of sphingomyelin-depleted membranes. The phenomenon of hot-cold hemolysis may be a consequence of the temperature dependence of divalent ion stabilization.", "contents": "Phenomenon of hot-cold hemolysis: chelator-induced lysis of sphingomyelinase-treated erythrocytes. Staphylococcus aureus produces a phospholipase C specific for sphingomyelin (beta-hemolysin). Erythrocytes with approximately 50% sphingomyelin in their membranes, e.g., from sheep, have been shown to have up to 60% of this phospholipid hydrolyzed by this enzyme at 37 C in isotonic buffered saline without hemolysis. Cooling of sphingomyelinase C-treated erythrocytes to 4 C causes complete lysis of the cells, a phenomenon known as hot-cold hemolysis. The addition of ethylenediaminetetraacetate (EDTA) to sheep erythrocytes preincubated with sphingomyelinase C was found to induce rapid hemolysis at 37 C. The treated cells became susceptible to chelator-induced hemolysis and to hot-cold hemolysis simultaneously, and the degree of lysis of both mechanisms increased equally with prolonged preincubation with sphingomyelinase C. Erythrocytes of species not readily susceptible to hot-cold hemolysis were equally insusceptible to chelator-induced lysis. Chelators of the EDTA series were the most effective, whereas chelators more specific for Ca2+, Zn2+, Fe2+, Cu2+, and Mg2+ were without effect. The rate of chelator-induced lysis was dependent on the preincubation period with beta-hemolysin and on the concentration of chelator added. The optimal concentration of EDTA was found to equal the amount of exogenously added Mg2+, a cation necessary for sphingomyelinase C activity. Hypotonicity increased the rate of chelator-induced hemolysis, whereas increasing the osmotic pressure to twice isotonic completely inhibited chelator-induced lysis. The data suggest that exogenously added and/or membrane-bound divalent cations are important for the stability of sphingomyelin-depleted membranes. The phenomenon of hot-cold hemolysis may be a consequence of the temperature dependence of divalent ion stabilization."}
{"id": "PMID:336", "title": "In vitro antagonism of the mediators of allergy by a benzopyrano-benzopyran carboxylic acid PR-D-92-EA.", "content": "PR-D-92-EA was tested on isolated guinea pig ileum and rat stomach strips for activity against mediators probably released after allergen antibody union. It antagonized the response produced by histamine, bradykinin, serotonin, prostaglandin E2, prostaglandin F2ALPHA and slow-reacting substance of anaphylaxis (SRS-A). The concentrations which blocked 50% of the response were 150, 145, 92, 70, 47, and 32 mug/ml, respectively. This compound may be useful in the treatment of allergic conditions.", "contents": "In vitro antagonism of the mediators of allergy by a benzopyrano-benzopyran carboxylic acid PR-D-92-EA. PR-D-92-EA was tested on isolated guinea pig ileum and rat stomach strips for activity against mediators probably released after allergen antibody union. It antagonized the response produced by histamine, bradykinin, serotonin, prostaglandin E2, prostaglandin F2ALPHA and slow-reacting substance of anaphylaxis (SRS-A). The concentrations which blocked 50% of the response were 150, 145, 92, 70, 47, and 32 mug/ml, respectively. This compound may be useful in the treatment of allergic conditions."}
{"id": "PMID:337", "title": "Tyrosine aminotransferase induction in normal and tumor-bearing chickens.", "content": "Tyrosine aminotransferase (TAT) induction by glucagon and dexamethasone in the liver of tumor-bearing chickens was studied and compared with induction in healthy animals. The transplantable tumor was caused by inoculation of cells from a cell line induced by MC29 avian leukosis virus. TAT was hardly detectable in tumor tissue of control and dexamethasone-treated chickens, but it was induced by glucagon to levels which were significant although very low when compared to those in host liver or the liver of non-tumor-bearing controls after glucagon treatment. Dexamethasone failed to induce TAT in host liver at 8 A.M. while it significantly indiced TAT in the normal liver at the same time of the day. Similar failure of TAT induction was not detectable when glucagon was used instead of dexamethasone. Furthermore, it was found that diurnal variations in basal and dexamethasone or glucagon-induced TAT levels are considerably mitigated in host liver as compared to those observed in the liver of healthy animals. The possible reasons for these findings are discussed.", "contents": "Tyrosine aminotransferase induction in normal and tumor-bearing chickens. Tyrosine aminotransferase (TAT) induction by glucagon and dexamethasone in the liver of tumor-bearing chickens was studied and compared with induction in healthy animals. The transplantable tumor was caused by inoculation of cells from a cell line induced by MC29 avian leukosis virus. TAT was hardly detectable in tumor tissue of control and dexamethasone-treated chickens, but it was induced by glucagon to levels which were significant although very low when compared to those in host liver or the liver of non-tumor-bearing controls after glucagon treatment. Dexamethasone failed to induce TAT in host liver at 8 A.M. while it significantly indiced TAT in the normal liver at the same time of the day. Similar failure of TAT induction was not detectable when glucagon was used instead of dexamethasone. Furthermore, it was found that diurnal variations in basal and dexamethasone or glucagon-induced TAT levels are considerably mitigated in host liver as compared to those observed in the liver of healthy animals. The possible reasons for these findings are discussed."}
{"id": "PMID:338", "title": "A behavior modification training program for staff working with drug addicts.", "content": "This paper described a Behavior Modification Training Program, emphasizing self-control, for staff working with drug addicts. The program, which is primarily geared toward the training of paraprofessionals, takes place in ten 1-1/2 hour sessions and includes an overview of behavior modification as well as instruction in techniques of relaxation, desensitization, self-image improvement, behavior analysis, behavior control, assertive training, rational thinking, and how to set up and run similar behavior modification training programs for staff and patients. Since this training began at the New Jersey Neuropsychiatric Institute in November 1971, a total of 898 staff members, mostly paraprofessionals working with addicts, alcoholics, mentally ill patients, and inmates, including 53 from our own institution, 576 persons from other facilities in New Jersey, and 269 from facilities in other states, have been trained, while 2,021 patients have been trained in similar programs. Most of this training has been accomplished by paraprofessionals. Preliminary evaluation data have been promising and the response of participants enthusiastic.", "contents": "A behavior modification training program for staff working with drug addicts. This paper described a Behavior Modification Training Program, emphasizing self-control, for staff working with drug addicts. The program, which is primarily geared toward the training of paraprofessionals, takes place in ten 1-1/2 hour sessions and includes an overview of behavior modification as well as instruction in techniques of relaxation, desensitization, self-image improvement, behavior analysis, behavior control, assertive training, rational thinking, and how to set up and run similar behavior modification training programs for staff and patients. Since this training began at the New Jersey Neuropsychiatric Institute in November 1971, a total of 898 staff members, mostly paraprofessionals working with addicts, alcoholics, mentally ill patients, and inmates, including 53 from our own institution, 576 persons from other facilities in New Jersey, and 269 from facilities in other states, have been trained, while 2,021 patients have been trained in similar programs. Most of this training has been accomplished by paraprofessionals. Preliminary evaluation data have been promising and the response of participants enthusiastic."}
{"id": "PMID:339", "title": "A kinetic study of the hydrolysis of N-acetyl dehydroalanine methyl ester.", "content": "Hydrolysis rates of N-acetyl dehydroalanine methyl ester (methyl 2-acetamidoacrylate) and related model compounds were measured in aqueous, organic and mixed aqueous media. Adding dimethylsulfoxide (DMSO) to water, retarded hydrolysis of the ester by a factor of 2 to 500, depending on the pH of the medium and concentration of DMSO. Ethanol also slowed hydrolysis, but the effect was not so pronounced. Related studies show that the acetamido group C-N bond of sodium 2-acetamido-acrylate is hydrolyzed only about 1/130 as fast as the ester group C-O bond. Aqueous dimethyl sulfoxide should by a useful medium for synthesis of peptide, amino acid and protein derivatives of N-acetyl dehydroalanine methyl ester.", "contents": "A kinetic study of the hydrolysis of N-acetyl dehydroalanine methyl ester. Hydrolysis rates of N-acetyl dehydroalanine methyl ester (methyl 2-acetamidoacrylate) and related model compounds were measured in aqueous, organic and mixed aqueous media. Adding dimethylsulfoxide (DMSO) to water, retarded hydrolysis of the ester by a factor of 2 to 500, depending on the pH of the medium and concentration of DMSO. Ethanol also slowed hydrolysis, but the effect was not so pronounced. Related studies show that the acetamido group C-N bond of sodium 2-acetamido-acrylate is hydrolyzed only about 1/130 as fast as the ester group C-O bond. Aqueous dimethyl sulfoxide should by a useful medium for synthesis of peptide, amino acid and protein derivatives of N-acetyl dehydroalanine methyl ester."}
{"id": "PMID:340", "title": "The ophthalmologist's office: planning and practice. Patient traffic flow and use of paramedical personnel.", "content": "In order for the ophthalmologist to achieve the greatest earning power and personal satisfaction, he or she must devise traffic flow techniques that efficiently allow for maximum utilization of all examining areas and paramedical personnel in the office without dehumanizing patients. By delegating as much responsibility as possible to staff, the ophthalmologist will have the opportunity of performing his or her specialized skills to the fullest extent, and therefore will achieve optimal personal gratification. This emotional reward indemnifies the future of private practice, because it can exist only in the presence of a close patient-physician relationship, which is the cornerstone of the private practice of ophthalmology.", "contents": "The ophthalmologist's office: planning and practice. Patient traffic flow and use of paramedical personnel. In order for the ophthalmologist to achieve the greatest earning power and personal satisfaction, he or she must devise traffic flow techniques that efficiently allow for maximum utilization of all examining areas and paramedical personnel in the office without dehumanizing patients. By delegating as much responsibility as possible to staff, the ophthalmologist will have the opportunity of performing his or her specialized skills to the fullest extent, and therefore will achieve optimal personal gratification. This emotional reward indemnifies the future of private practice, because it can exist only in the presence of a close patient-physician relationship, which is the cornerstone of the private practice of ophthalmology."}
{"id": "PMID:342", "title": "Computer evaluation of the effect of urecholine on the spontaneous activity of smooth muscle from the urinary bladder of the rabbit.", "content": "The spontaneous activity exhibited in vitro by smooth muscle strips from the urinary bladder of the rabbit under the influence of Urecholine in concentrations from 0.3 to 30 muM has been characterized in terms of three parameters: mean tension, frequency of contraction, and contractile deviation, all obtained by computer an alysis. While mean tension and frequency monotonically increased with concentration, the contractile deviation rose to a peak in the vicinity of 3.0 to 6.0 muM and thereafter decreased. At concentrations less than 10 muM the contractile patterns were almost periodic, while at 10 and 30 muM, the patterns became highly erratic. Histologic examination of a limited number of tissues showed longitudinally oriented muscle bundles with multiple anastomosing.", "contents": "Computer evaluation of the effect of urecholine on the spontaneous activity of smooth muscle from the urinary bladder of the rabbit. The spontaneous activity exhibited in vitro by smooth muscle strips from the urinary bladder of the rabbit under the influence of Urecholine in concentrations from 0.3 to 30 muM has been characterized in terms of three parameters: mean tension, frequency of contraction, and contractile deviation, all obtained by computer an alysis. While mean tension and frequency monotonically increased with concentration, the contractile deviation rose to a peak in the vicinity of 3.0 to 6.0 muM and thereafter decreased. At concentrations less than 10 muM the contractile patterns were almost periodic, while at 10 and 30 muM, the patterns became highly erratic. Histologic examination of a limited number of tissues showed longitudinally oriented muscle bundles with multiple anastomosing."}
{"id": "PMID:343", "title": "Characteristics of the non-occluded form of a nuclear polyhedrosis virus.", "content": "Non-occluded virions of a nuclear polyhedrosis virus of the alfalfa looper, Autographa californica, found in the medium of cell cultures of infected fall armyworm, Spodopter frugiperda, and in the hemolymph of infected S. frugiperda larvae were partially characterized by biological, chemical and physical methods. Also, the rate of appearance of the virions was studied in cell culture and the host insect to determine maximum virion production. Virions obtained from both sources were heat-sensitive, acid-labile and inactivated by several organic solvents. The non-occluded virions found in the insect cell culture fluid and in the hemolymph were identical, and both were enveloped nucleocapsids. Visualization of the fragilely enveloped nucleocapsid was accomplished only after fixation with glutaraldehyde. Differences between the non-occluded and occluded virions of nuclear polyhedrosis viruses are discussed.", "contents": "Characteristics of the non-occluded form of a nuclear polyhedrosis virus. Non-occluded virions of a nuclear polyhedrosis virus of the alfalfa looper, Autographa californica, found in the medium of cell cultures of infected fall armyworm, Spodopter frugiperda, and in the hemolymph of infected S. frugiperda larvae were partially characterized by biological, chemical and physical methods. Also, the rate of appearance of the virions was studied in cell culture and the host insect to determine maximum virion production. Virions obtained from both sources were heat-sensitive, acid-labile and inactivated by several organic solvents. The non-occluded virions found in the insect cell culture fluid and in the hemolymph were identical, and both were enveloped nucleocapsids. Visualization of the fragilely enveloped nucleocapsid was accomplished only after fixation with glutaraldehyde. Differences between the non-occluded and occluded virions of nuclear polyhedrosis viruses are discussed."}
{"id": "PMID:344", "title": "Degradation of myxovirus virion RNA by periodate.", "content": "Extensively degraded RNA was isolated from virions of influenza virus which had been oxidized with sodium m-periodate. Similarly, although to a lesser extent, RNA isolated from periodate-treated ribonucleoprotein of influenza virus was also degraded. In contrast, influenza virus RNA, if first freed from other virion components, was not degraded by periodate oxidation.", "contents": "Degradation of myxovirus virion RNA by periodate. Extensively degraded RNA was isolated from virions of influenza virus which had been oxidized with sodium m-periodate. Similarly, although to a lesser extent, RNA isolated from periodate-treated ribonucleoprotein of influenza virus was also degraded. In contrast, influenza virus RNA, if first freed from other virion components, was not degraded by periodate oxidation."}
{"id": "PMID:345", "title": "Failure of rubella virus to replicate in mosquitos.", "content": "Rubella virus failed to replicate in mosquitoes (Aedes albopictus and Culex fatigans) following parenteral inoculation. The virus demonstrated in mosquitoes tested immediately after inoculation but was not detected in insects sampled 7, 14 and 21 days postinoculation. This experiment provides further evidence that rubella is not an arbovirus, but does not invalidate its classification as a togavirus.", "contents": "Failure of rubella virus to replicate in mosquitos. Rubella virus failed to replicate in mosquitoes (Aedes albopictus and Culex fatigans) following parenteral inoculation. The virus demonstrated in mosquitoes tested immediately after inoculation but was not detected in insects sampled 7, 14 and 21 days postinoculation. This experiment provides further evidence that rubella is not an arbovirus, but does not invalidate its classification as a togavirus."}
{"id": "PMID:346", "title": "Treatment of severe hypertension with minoxidil.", "content": "Minoxidil in daily doses of 6 to 40 mg was administered to 11 patients with severe hypertension. Two patients died of causes unrelated to the drug and one patient withdrew from the study. Blood pressure was controlled in the remaining eight subjects, who received the drug for periods ranging from 5 to 40 months. In three patients minoxidil could subsequently be replaced by conventional antihypertensive therapy. Adverse effects of minoxidil included fluid retention (as assessed by edema and plasma volume studies), nonspecific ECG changes, hypertrichosis and conjunctival redness. Concomitant administration of diuretic and beta-adrenergic blocking agents resulted in excellent tolerance of the treatment and high patient compliance.", "contents": "Treatment of severe hypertension with minoxidil. Minoxidil in daily doses of 6 to 40 mg was administered to 11 patients with severe hypertension. Two patients died of causes unrelated to the drug and one patient withdrew from the study. Blood pressure was controlled in the remaining eight subjects, who received the drug for periods ranging from 5 to 40 months. In three patients minoxidil could subsequently be replaced by conventional antihypertensive therapy. Adverse effects of minoxidil included fluid retention (as assessed by edema and plasma volume studies), nonspecific ECG changes, hypertrichosis and conjunctival redness. Concomitant administration of diuretic and beta-adrenergic blocking agents resulted in excellent tolerance of the treatment and high patient compliance."}
{"id": "PMID:350", "title": "[Parotid secretion and its pharmacologically induced variants (author's transl)].", "content": "The secretion of alpha-amylase and electrolytes by the parotid gland is now well understood and similarities exist in this respect between man and animals. Many modern drugs influence parotid secretion and morphology, and these are discussed.", "contents": "[Parotid secretion and its pharmacologically induced variants (author's transl)]. The secretion of alpha-amylase and electrolytes by the parotid gland is now well understood and similarities exist in this respect between man and animals. Many modern drugs influence parotid secretion and morphology, and these are discussed."}
{"id": "PMID:349", "title": "Acute renal failure.", "content": "Acute renal failure is a life-threatening situation for which satisfactory treatment is currently available. Death is usually related to concomitant infection rather than uremia. Prompt recognition and treatment of underlying factors that predispose to renal insufficiency can frequently prevent the development of intrinsic acute renal failure.", "contents": "Acute renal failure. Acute renal failure is a life-threatening situation for which satisfactory treatment is currently available. Death is usually related to concomitant infection rather than uremia. Prompt recognition and treatment of underlying factors that predispose to renal insufficiency can frequently prevent the development of intrinsic acute renal failure."}
{"id": "PMID:354", "title": "Analysis of pesticides by chemical derivatization. I. a new procedure for the formation of 2-chloroethyl esters of ten herbicidal acids.", "content": "A new esterification procedure was developed to form 2-chloroethyl esters for 10 common herbicidal acids, using dicyclohexyl carbodiimide and 2-chloroethanol. This reagent was found to be more desirable than the commonly used boron trichloride/2-chloroethanol reagent. Maximum esterification was given for picloram at a lower reaction temperature with a shorter reaction time. Also, maximum esterification of dicamba and 2,3,6-TBA was achieved. The boron trichloride/2-chlorethanol gave poor or little esterification with these 2 acids under the various conditions investigated. The effect of solvents on esterification with the 2 reagents was also explored.", "contents": "Analysis of pesticides by chemical derivatization. I. a new procedure for the formation of 2-chloroethyl esters of ten herbicidal acids. A new esterification procedure was developed to form 2-chloroethyl esters for 10 common herbicidal acids, using dicyclohexyl carbodiimide and 2-chloroethanol. This reagent was found to be more desirable than the commonly used boron trichloride/2-chloroethanol reagent. Maximum esterification was given for picloram at a lower reaction temperature with a shorter reaction time. Also, maximum esterification of dicamba and 2,3,6-TBA was achieved. The boron trichloride/2-chlorethanol gave poor or little esterification with these 2 acids under the various conditions investigated. The effect of solvents on esterification with the 2 reagents was also explored."}
{"id": "PMID:353", "title": "Local control of pulmonary resistance and lung compliance in the canine lung.", "content": "Local control of pulmonary resistance and lung compliance was studied in the in situ left lower lobe of the canine lung. Recirculation of blood through the lobe while the Pco2 of the ventilatory gas was varied resulted in an increase in resistance and a decrease in compliance only when the pulmonary venous pH was greater than 7.42. Alternating sodium bicarbonate and lactic acid infusion while alveolar Pco2 was maintained below 5 mmHg demonstrated the dependence of the hypocapnic response on the acid-base status of the blood perfusing the respiratory airways. The increase in resistance and decrease in compliance observed at a pulmonary venous pH of 7.64 was comparable to that observed after lobar pulmonary artery occlusion. Varying degrees of hypoxia did not significantly affect bronchomotor tone, nor was the bronchoconstriction following lobar pulmonary artery occlusion affected by the hypoxia. Vagal stimulation superimposed on a stepwise increase in pulmonary venous pH from 7.32 to 7.62 resulted in an increase in resistance which paralleled the increase in resistance when pulmonary venous pH alone was increased. Compliance was not significantly affected by vagal stimulation at any level of pulmonary venous pH.", "contents": "Local control of pulmonary resistance and lung compliance in the canine lung. Local control of pulmonary resistance and lung compliance was studied in the in situ left lower lobe of the canine lung. Recirculation of blood through the lobe while the Pco2 of the ventilatory gas was varied resulted in an increase in resistance and a decrease in compliance only when the pulmonary venous pH was greater than 7.42. Alternating sodium bicarbonate and lactic acid infusion while alveolar Pco2 was maintained below 5 mmHg demonstrated the dependence of the hypocapnic response on the acid-base status of the blood perfusing the respiratory airways. The increase in resistance and decrease in compliance observed at a pulmonary venous pH of 7.64 was comparable to that observed after lobar pulmonary artery occlusion. Varying degrees of hypoxia did not significantly affect bronchomotor tone, nor was the bronchoconstriction following lobar pulmonary artery occlusion affected by the hypoxia. Vagal stimulation superimposed on a stepwise increase in pulmonary venous pH from 7.32 to 7.62 resulted in an increase in resistance which paralleled the increase in resistance when pulmonary venous pH alone was increased. Compliance was not significantly affected by vagal stimulation at any level of pulmonary venous pH."}
{"id": "PMID:356", "title": "Inactivation of citrate lyase from Rhodopseudomonas gelatinosa by a specific deacetylase and inhibition of this inactivation by L-(+1-glutamate.", "content": "A previously unrecognized enzyme, citrate lyase deacetylase, has been purified about 140-fold from cell extracts of Rhodopseudomonas gelatinosa. It catalyzed the conversion of enzymatically active acetyl-S-citrate lyase into the inactive HS-form and acetate. The enzyme exhibited an optimal rate of inactivation at pH 8.1. Because of the instability of acetyl-S-citrate lyase at acidic and alkaline pH values, all assays were carried out at pH 7.2, where the spontaneous hydrolysis of the acetyl-S-citrate lyase was negligible and deacetylase showed 70% of the activity at pH 8.1. The apparent Km value for citrate lyase was 10(-7) M at pH 7.2 and 30 C. The activity of the deacetylase was restricted to the citrate lyase from R. gelatinosa. The corresponding lyases from Enterobacter aerogenes (formerly Klebsiella aerogenes) and Streptococcus diacetilactis were not deacetylated; likewise, thioesters such as acetyl-S coenzyme A, acetoacetyl-S coenzyme A, and N-acetyl-S-acetyl-cysteamine were also not hydrolyzed. Citrate lyase deacetylase was present in very small amounts in cells of R. gelatinosa grown with acetate or succinate; it was induced by citrate along with the citrate lyase. L-(+)-Glutamate strongly inhibited the deacetylase. Fifty percent inhibition was obtained at a concentration of 1.4 X 10(-4) L-(+)-glutamate. D-(-)-Glutamate, alpha-ketoglutarate, L-alpha-hydroxyglutarate, L-(-)-proline, and other metabolites were less effective.", "contents": "Inactivation of citrate lyase from Rhodopseudomonas gelatinosa by a specific deacetylase and inhibition of this inactivation by L-(+1-glutamate. A previously unrecognized enzyme, citrate lyase deacetylase, has been purified about 140-fold from cell extracts of Rhodopseudomonas gelatinosa. It catalyzed the conversion of enzymatically active acetyl-S-citrate lyase into the inactive HS-form and acetate. The enzyme exhibited an optimal rate of inactivation at pH 8.1. Because of the instability of acetyl-S-citrate lyase at acidic and alkaline pH values, all assays were carried out at pH 7.2, where the spontaneous hydrolysis of the acetyl-S-citrate lyase was negligible and deacetylase showed 70% of the activity at pH 8.1. The apparent Km value for citrate lyase was 10(-7) M at pH 7.2 and 30 C. The activity of the deacetylase was restricted to the citrate lyase from R. gelatinosa. The corresponding lyases from Enterobacter aerogenes (formerly Klebsiella aerogenes) and Streptococcus diacetilactis were not deacetylated; likewise, thioesters such as acetyl-S coenzyme A, acetoacetyl-S coenzyme A, and N-acetyl-S-acetyl-cysteamine were also not hydrolyzed. Citrate lyase deacetylase was present in very small amounts in cells of R. gelatinosa grown with acetate or succinate; it was induced by citrate along with the citrate lyase. L-(+)-Glutamate strongly inhibited the deacetylase. Fifty percent inhibition was obtained at a concentration of 1.4 X 10(-4) L-(+)-glutamate. D-(-)-Glutamate, alpha-ketoglutarate, L-alpha-hydroxyglutarate, L-(-)-proline, and other metabolites were less effective."}
{"id": "PMID:357", "title": "Novel type of murein transglycosylase in Escherichia coli.", "content": "The purification and properties of a novel type of murein transglycosylase from Escherichia coli are described. The purified enzyme appears as a single band on sodium dodecyl sulfate-polyacrylamide gels and has an apparent molecular weight of approximately 65,000 as estimated by gel filtration and gel electrophoresis. It degrades pure murein sacculi from E. coli almost completely into low-molecular-weight products. The two prominent muropeptide fragments in the digest are the disaccharide-tripeptide N-acetylglucosamine-N-acetylmuramic acid-L-alanine-D-iso-glutamic acid-meso-diaminopimelic acid and the corresponding disaccharide-tetrapeptide N-acetylglucosamine-N-acetylmuramic acid-L-alanine-D-iso-glutamic acid-meso-diaminopimelic acid-D-alanine. The unique feature of these compounds is that the disaccharide has no reducing end group and that the muramic acid residue possesses an internal 1 leads to 6 anhydro linkage. The new lytic enzyme is designated as a murein: murein transglycosylase. Its possible role in the rearrangement of murein during cell growth and division is discussed.", "contents": "Novel type of murein transglycosylase in Escherichia coli. The purification and properties of a novel type of murein transglycosylase from Escherichia coli are described. The purified enzyme appears as a single band on sodium dodecyl sulfate-polyacrylamide gels and has an apparent molecular weight of approximately 65,000 as estimated by gel filtration and gel electrophoresis. It degrades pure murein sacculi from E. coli almost completely into low-molecular-weight products. The two prominent muropeptide fragments in the digest are the disaccharide-tripeptide N-acetylglucosamine-N-acetylmuramic acid-L-alanine-D-iso-glutamic acid-meso-diaminopimelic acid and the corresponding disaccharide-tetrapeptide N-acetylglucosamine-N-acetylmuramic acid-L-alanine-D-iso-glutamic acid-meso-diaminopimelic acid-D-alanine. The unique feature of these compounds is that the disaccharide has no reducing end group and that the muramic acid residue possesses an internal 1 leads to 6 anhydro linkage. The new lytic enzyme is designated as a murein: murein transglycosylase. Its possible role in the rearrangement of murein during cell growth and division is discussed."}
{"id": "PMID:358", "title": "Formation and cleavage of 2-keto-3-deoxygluconate by 2-keto-3-deoxygluconate aldolase of Aspergillus niger.", "content": "2-Keto-3-deoxygluconate aldolase of Aspergillus niger, an enzyme that has not been reported previously, was purified 468-fold. Maximal activity was obtained at pH 8.0 and 50 C. The enzyme exhibited relative stereochemical specificity with respect to glyceraldehyde. The Km values for 2-keto-3-deoxygluconate, glyceraldehyde, and pyruvate were 10, 13.3, and 3.0 mM, respectively. The effects of some compounds and inhibitors on enzyme activity were examined. Stability of the enzyme under different conditions was investigated. The equilibrium constant was about 0.33 X 10(-3) M.", "contents": "Formation and cleavage of 2-keto-3-deoxygluconate by 2-keto-3-deoxygluconate aldolase of Aspergillus niger. 2-Keto-3-deoxygluconate aldolase of Aspergillus niger, an enzyme that has not been reported previously, was purified 468-fold. Maximal activity was obtained at pH 8.0 and 50 C. The enzyme exhibited relative stereochemical specificity with respect to glyceraldehyde. The Km values for 2-keto-3-deoxygluconate, glyceraldehyde, and pyruvate were 10, 13.3, and 3.0 mM, respectively. The effects of some compounds and inhibitors on enzyme activity were examined. Stability of the enzyme under different conditions was investigated. The equilibrium constant was about 0.33 X 10(-3) M."}
{"id": "PMID:359", "title": "Chemotaxis of a motile Streptococcus toward sugars and amino acids.", "content": "A motile Streptococcus was isolated and its chemotactic behavior toward sugars and amino acids was studied. Motility was optimal in the presence of an exogenous energy source and a nonionic detergent, e.g., Tween 80 or Brij-36. Both glucose and pyruvate could serve as energy source. Chemotaxis toward leucine was optimal at pH 7 to 8.5 and a temperature between 30 and 37 C. The Streptococcus showed a chemotactic response toward a variety of sugars. All commonly occurring L-amino acids, except alanine, asparagine, aspartate, glutamate, arginine, and lysine, were attractants. From concentration response curves the thresholds, peak concentrations, and optimal responses were determined.", "contents": "Chemotaxis of a motile Streptococcus toward sugars and amino acids. A motile Streptococcus was isolated and its chemotactic behavior toward sugars and amino acids was studied. Motility was optimal in the presence of an exogenous energy source and a nonionic detergent, e.g., Tween 80 or Brij-36. Both glucose and pyruvate could serve as energy source. Chemotaxis toward leucine was optimal at pH 7 to 8.5 and a temperature between 30 and 37 C. The Streptococcus showed a chemotactic response toward a variety of sugars. All commonly occurring L-amino acids, except alanine, asparagine, aspartate, glutamate, arginine, and lysine, were attractants. From concentration response curves the thresholds, peak concentrations, and optimal responses were determined."}
{"id": "PMID:360", "title": "Phospholipase D activity of gram-negative bacteria.", "content": "A phospholipase hydrolyzing cardiolipin to phosphatidic acid and phosphatidyl glycerol was characterized in gram-negative bacteria but was absent in preparations of gram-positive bacteria, Saccharomyces cerevisiae, and rat liver mitochondria. In cell-free extracts of Escherichia coli, Salmonella typhimurium, Proteus vulgaris, and Pseudomonase aeruginosa, this cardiolipin-hydrolyzing enzyme had similar pH and Mg2+ requirements and displayed a specificity which excluded phosphatidyl glycerol and phosphatidyl ethanolamine as substrates.", "contents": "Phospholipase D activity of gram-negative bacteria. A phospholipase hydrolyzing cardiolipin to phosphatidic acid and phosphatidyl glycerol was characterized in gram-negative bacteria but was absent in preparations of gram-positive bacteria, Saccharomyces cerevisiae, and rat liver mitochondria. In cell-free extracts of Escherichia coli, Salmonella typhimurium, Proteus vulgaris, and Pseudomonase aeruginosa, this cardiolipin-hydrolyzing enzyme had similar pH and Mg2+ requirements and displayed a specificity which excluded phosphatidyl glycerol and phosphatidyl ethanolamine as substrates."}
{"id": "PMID:361", "title": "Pyridine nucleotide-linked oxidation of methanol in methanol-assimilating yeasts.", "content": "An alcohol dehydrogenase linked to nicotinamide adenine dinucleotide and requiring glutathione has been isolated and partially purified from two methanol-assimilating yeasts. It differs from previously described methanol-oxidizing enzymes in pH optima, electron acceptor specificity, substrate specificity, inhibition pattern, and stability.", "contents": "Pyridine nucleotide-linked oxidation of methanol in methanol-assimilating yeasts. An alcohol dehydrogenase linked to nicotinamide adenine dinucleotide and requiring glutathione has been isolated and partially purified from two methanol-assimilating yeasts. It differs from previously described methanol-oxidizing enzymes in pH optima, electron acceptor specificity, substrate specificity, inhibition pattern, and stability."}
{"id": "PMID:362", "title": "Expression of the hut operons of Salmonella typhimurium in Klebsiella aerogenes and in Escherichia coli.", "content": "The normal hut (histidine utilization) operons, as well as those with mutations affecting the regulation of their expression, of Salmonella typhimurium were introduced on an F' episome into cells of S. typhimurium and Klebsiella aerogenes whose chromosomal hut genes had been deleted and into cells of Escherichia coli, whose chromosome does not carry hut genes. The episomal hut operons respond in a manner very similar to induction and catabolite repression in all three organisms. The small differences found reflect both different abilities to take up inducers from the medium and different degrees of catabolite repression exerted by glucose.", "contents": "Expression of the hut operons of Salmonella typhimurium in Klebsiella aerogenes and in Escherichia coli. The normal hut (histidine utilization) operons, as well as those with mutations affecting the regulation of their expression, of Salmonella typhimurium were introduced on an F' episome into cells of S. typhimurium and Klebsiella aerogenes whose chromosomal hut genes had been deleted and into cells of Escherichia coli, whose chromosome does not carry hut genes. The episomal hut operons respond in a manner very similar to induction and catabolite repression in all three organisms. The small differences found reflect both different abilities to take up inducers from the medium and different degrees of catabolite repression exerted by glucose."}
{"id": "PMID:363", "title": "Regulation of the hut operons of Salmonella typhimurium and Klebsiella aerogenes by the heterologous hut repressors.", "content": "In merodiploid strains of Klebsiella aerogenes with chromosomal hut genes of K. aerogenes and episomal hut genes of Salmonella typhimurium, the repressor of either species can regulate the hut operons of the other species. The repression exerted by the homologous repressor on the left-hand hut operon is, in both organisms, stronger than that exerted by the heterologous repressor.", "contents": "Regulation of the hut operons of Salmonella typhimurium and Klebsiella aerogenes by the heterologous hut repressors. In merodiploid strains of Klebsiella aerogenes with chromosomal hut genes of K. aerogenes and episomal hut genes of Salmonella typhimurium, the repressor of either species can regulate the hut operons of the other species. The repression exerted by the homologous repressor on the left-hand hut operon is, in both organisms, stronger than that exerted by the heterologous repressor."}
{"id": "PMID:364", "title": "Transport of molybdate by Clostridium pasteurianum.", "content": "The transport of 99MoO42- into dinitrogen-fixing cells of Clostridium pasteurianum was investigated. Transport of molybdate in this organism is energy dependent; sucrose is required in the minimal media, and the system is inhibited by the glycolysis inhibitors, NaF, iodoacetic acid, and arsenate. The cells accumulate molybdate against a concentration gradient, and the uptake shows a marked dependence on temperature (optimum 37 C) and pH (optimum 6.0). The rate of molybdate uptake with increasing molybdate concentrations shows saturation kinetics with an apparent Km and Vmax of 4.8 X 10(-5) M and 55 nmol/g of dry cells per min, respectively. Inhibition studies with the anions SO42-, S2O32-, WO42-, and VO32- show that SO42- and WO42- competitively inhibit MoO42- uptake (apparent Ki [SO42-] is 3.0 X 10(-5) M; apparent Ki [WO42-] is 2.4 X 10(-5), whereas S2O32- and VO32- have no inhibitory effect. Exchange experiments with MoO42- show that only a small percentage of the 99MoO42- taken up by the cells is exchangeable. Exchange experiments with WO42- and SO42- indicate that once inside the cells WO42- and SO42- cannot substitute for MoO42-.", "contents": "Transport of molybdate by Clostridium pasteurianum. The transport of 99MoO42- into dinitrogen-fixing cells of Clostridium pasteurianum was investigated. Transport of molybdate in this organism is energy dependent; sucrose is required in the minimal media, and the system is inhibited by the glycolysis inhibitors, NaF, iodoacetic acid, and arsenate. The cells accumulate molybdate against a concentration gradient, and the uptake shows a marked dependence on temperature (optimum 37 C) and pH (optimum 6.0). The rate of molybdate uptake with increasing molybdate concentrations shows saturation kinetics with an apparent Km and Vmax of 4.8 X 10(-5) M and 55 nmol/g of dry cells per min, respectively. Inhibition studies with the anions SO42-, S2O32-, WO42-, and VO32- show that SO42- and WO42- competitively inhibit MoO42- uptake (apparent Ki [SO42-] is 3.0 X 10(-5) M; apparent Ki [WO42-] is 2.4 X 10(-5), whereas S2O32- and VO32- have no inhibitory effect. Exchange experiments with MoO42- show that only a small percentage of the 99MoO42- taken up by the cells is exchangeable. Exchange experiments with WO42- and SO42- indicate that once inside the cells WO42- and SO42- cannot substitute for MoO42-."}
{"id": "PMID:365", "title": "3-Deoxy-D-arabino-heptulosonic acid 7-phosphate synthase mutants of Salmonella typhimurium.", "content": "The first committed step of aromatic amino acid biosynthesis in Salmonella typhimurium was shown to be catalyzed by three isoenzymes of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) synthase. Mutations in each of the genes specifying the isoenzymes were isolated and mapped. aroG, the structural gene for the phenylalanine-inhibitable isoenzyme, was linked to gal, and aroH, the structural gene for the tryptophan-inhibitable isoenzyme, was linked to aroE. aroF, the structural gene for the tyrosine-inhibitable isoenzyme, was linked to pheA and tyrA, which specify the phenylalanine- and tyrosine-specific branch-point enzymes, respectively. The phenylalanine-inhibitable isoenzyme was the predominant DAHP synthase in wild-type cells, and only the tryosine-inhibitable isoenzyme was completely repressed, as well as inhibited, by low levels of its allosteric effector. The DAHP synthase isoenzymes were separated by chromatography on diethylaminoethyl-cellulose with a phosphate gradient which contained enolpyruvate phosphate to protect the otherwise unstable phenylalanine-inhibitable isoenzyme. No cross-inhibition of either the tyrosine- or phenylalanine-inhibitable isoenzyme was observed at inhibitor concentrations up to 1 mM. The tryptophan-inhibitable isoenzyme was partially purified from extracts of a strain lacking the other two isoenzymes and shown to be inhibited about 30% by 1 mM tryptophan. A preliminary study of interference by tryptophan in the periodate-thiobarbiturate assay for DAHP suggested a combined effect of tryptophan and erythrose 4-phosphate, or an aldehydic compound resulting from degradation of erythrose 4-phosphate by periodate.", "contents": "3-Deoxy-D-arabino-heptulosonic acid 7-phosphate synthase mutants of Salmonella typhimurium. The first committed step of aromatic amino acid biosynthesis in Salmonella typhimurium was shown to be catalyzed by three isoenzymes of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) synthase. Mutations in each of the genes specifying the isoenzymes were isolated and mapped. aroG, the structural gene for the phenylalanine-inhibitable isoenzyme, was linked to gal, and aroH, the structural gene for the tryptophan-inhibitable isoenzyme, was linked to aroE. aroF, the structural gene for the tyrosine-inhibitable isoenzyme, was linked to pheA and tyrA, which specify the phenylalanine- and tyrosine-specific branch-point enzymes, respectively. The phenylalanine-inhibitable isoenzyme was the predominant DAHP synthase in wild-type cells, and only the tryosine-inhibitable isoenzyme was completely repressed, as well as inhibited, by low levels of its allosteric effector. The DAHP synthase isoenzymes were separated by chromatography on diethylaminoethyl-cellulose with a phosphate gradient which contained enolpyruvate phosphate to protect the otherwise unstable phenylalanine-inhibitable isoenzyme. No cross-inhibition of either the tyrosine- or phenylalanine-inhibitable isoenzyme was observed at inhibitor concentrations up to 1 mM. The tryptophan-inhibitable isoenzyme was partially purified from extracts of a strain lacking the other two isoenzymes and shown to be inhibited about 30% by 1 mM tryptophan. A preliminary study of interference by tryptophan in the periodate-thiobarbiturate assay for DAHP suggested a combined effect of tryptophan and erythrose 4-phosphate, or an aldehydic compound resulting from degradation of erythrose 4-phosphate by periodate."}
{"id": "PMID:367", "title": "Regulation of dihydrodipicolinate synthase during growth and sporulation of Bacillus cereus.", "content": "A four- to sixfold increase in specific activity of dihydrodipicolinic acid synthase was observed during sporulation of Bacillus cereus. The enzyme from cells harvested before and after the increase in specific activity appeared to be very similar as judged by pH optima, heat denaturation kinetics, apparent Michaelis constants, chromatography on diethylaminoethyl-cellulose and Sephadex G-200, and polyacrylamide gel electrophoresis. Studies with various combinations of amino acids and one of the enzyme substrates, pyruvate, failed to give evidence for control of the enzyme by activation, inhibition, repression, induction, or stabilization. Omission of calcium from the sporulation medium had no significant effect on the specific activity pattern of the enzyme as a function of age of culture.", "contents": "Regulation of dihydrodipicolinate synthase during growth and sporulation of Bacillus cereus. A four- to sixfold increase in specific activity of dihydrodipicolinic acid synthase was observed during sporulation of Bacillus cereus. The enzyme from cells harvested before and after the increase in specific activity appeared to be very similar as judged by pH optima, heat denaturation kinetics, apparent Michaelis constants, chromatography on diethylaminoethyl-cellulose and Sephadex G-200, and polyacrylamide gel electrophoresis. Studies with various combinations of amino acids and one of the enzyme substrates, pyruvate, failed to give evidence for control of the enzyme by activation, inhibition, repression, induction, or stabilization. Omission of calcium from the sporulation medium had no significant effect on the specific activity pattern of the enzyme as a function of age of culture."}
{"id": "PMID:366", "title": "Membrane location of a deoxyribonuclease implicated in the genetic transformation of Diplococcus pneumoniae.", "content": "The cellular localization of enzymes in Diplococcus pneumoniae was examined by fractionation of spheroplasts. A deoxyribonuclease implicated in the entry of deoxyribonucleic acid (DNA) into the cell during genetic transformation was located in the cell membrane. This enzyme, the major endonuclease of the cell (endonuclease I), which is necessary for the conversion of donor DNA to single strands inside the cell and oligonucleotides outside, thus could act at the cell surface. Another enzyme, the cell wall lysin (autolysin), was also found in the membrane fraction. Other enzymes, including amylomaltase, two exonucleases, and adenosine triphosphate-dependent deoxyribonuclease, and a restriction type endonuclease, were located in the cytosol within the cell. None of the enzymes examined were predominantly periplasmic in location. Spheroplasts were obtained spontaneously on incubation of pneumococcal cells in concentrated sugar solutions. The autolytic enzyme appears to be involved in this process. Cells that were physiologically competent to take up DNA formed osmotically sensitive spheroplasts two to three times faster than cells that were not in the competent state. Although some genetically incompetent mutants also formed spheroplasts more slowly, other such mutants formed them at the faster rate.", "contents": "Membrane location of a deoxyribonuclease implicated in the genetic transformation of Diplococcus pneumoniae. The cellular localization of enzymes in Diplococcus pneumoniae was examined by fractionation of spheroplasts. A deoxyribonuclease implicated in the entry of deoxyribonucleic acid (DNA) into the cell during genetic transformation was located in the cell membrane. This enzyme, the major endonuclease of the cell (endonuclease I), which is necessary for the conversion of donor DNA to single strands inside the cell and oligonucleotides outside, thus could act at the cell surface. Another enzyme, the cell wall lysin (autolysin), was also found in the membrane fraction. Other enzymes, including amylomaltase, two exonucleases, and adenosine triphosphate-dependent deoxyribonuclease, and a restriction type endonuclease, were located in the cytosol within the cell. None of the enzymes examined were predominantly periplasmic in location. Spheroplasts were obtained spontaneously on incubation of pneumococcal cells in concentrated sugar solutions. The autolytic enzyme appears to be involved in this process. Cells that were physiologically competent to take up DNA formed osmotically sensitive spheroplasts two to three times faster than cells that were not in the competent state. Although some genetically incompetent mutants also formed spheroplasts more slowly, other such mutants formed them at the faster rate."}
{"id": "PMID:368", "title": "D-Lactate dehydrogenase of Peptostreptococcus elsdenii.", "content": "D-Lactate dehydrogenase has been purified to near homogeneity from Peptostreptococcus elsdenii. As isolated, the enzyme contains flavine adenine dinucleotide and a tightly bound metal cofactor. Inactivation by ortho-phenanthroline occurs in two steps and is partially blocked by D-lactate. Reactivation by divalent metal ions occurs, with divalent zinc being the most effective. When ferricyanide is used as the electron acceptor, D-lactate has an apparent K0.5 of 3.3 M0.46; its binding is negatively cooperative with a Hill coefficient of 0.46. Replacement of ferricyanide by the other components of the electron transport system yields hyperbolic kinetics with an apparent Km for D-lactate of 26 mM. The apparent Km for ferricyanide is 2.2 X 10(-4) M. Phosphate and pyrophosphate compounds stimulate the D-lactate:ferricyanide activity. These properties suggest that interaction of this enzyme with other electron transport proteins in the chain may enhance D-lactate binding and, hence, the rate of electron transport.", "contents": "D-Lactate dehydrogenase of Peptostreptococcus elsdenii. D-Lactate dehydrogenase has been purified to near homogeneity from Peptostreptococcus elsdenii. As isolated, the enzyme contains flavine adenine dinucleotide and a tightly bound metal cofactor. Inactivation by ortho-phenanthroline occurs in two steps and is partially blocked by D-lactate. Reactivation by divalent metal ions occurs, with divalent zinc being the most effective. When ferricyanide is used as the electron acceptor, D-lactate has an apparent K0.5 of 3.3 M0.46; its binding is negatively cooperative with a Hill coefficient of 0.46. Replacement of ferricyanide by the other components of the electron transport system yields hyperbolic kinetics with an apparent Km for D-lactate of 26 mM. The apparent Km for ferricyanide is 2.2 X 10(-4) M. Phosphate and pyrophosphate compounds stimulate the D-lactate:ferricyanide activity. These properties suggest that interaction of this enzyme with other electron transport proteins in the chain may enhance D-lactate binding and, hence, the rate of electron transport."}
{"id": "PMID:369", "title": "Purification, new assay, and properties of coenzyme A transferase from Peptostreptococcus elsdenii.", "content": "Coenzyme A (CoA) transferase from Peptostreptococcus elsdenii has been purified and crystallized, and some of its properties have been established. The work was facilitated by a newly developed coupled and continuous spectrophotometric assay in which the disappearance of added acrylate could be followed at 245 nm. The rate-limiting conversion of acetyl- and beta-hydroxypropionyl CoA to acrylyl CoA by CoA transferase was followed by the non-rate-limiting conversion to beta-hydroxypropionyl CoA by excess crotonase. Thus, a small priming quantity of acetyl CoA served to generate acrylyl CoA, which, by hydration, generated beta-hydroxypropionyl CoA. This product then served to generate more acrylyl CoA in cyclic fashion. The net result was the CoA transferase-limited conversion of acrylate to beta-hydroxypropionate. The purified transferase has a molecular weight of 125,000 and is composed of two subunits of 63,000 each, as determined by disc gel electrophoresis. Short-chain-length monocarboxylic acids are substrates, whereas dicarboxylic or beta-ketocarboxylic acids are not. The reaction kinetics are typical of a ping-pong bi bi mechanism composed of two half reactions linked by a covalent enzyme intermediate. Incubation of the transferase with acetyl CoA in the absence of a fatty acid acceptor yielded a stable intermediate which, by absorption spectrophotometry, radioactivity measurements, reduction with borohydride, reactivity with hydroxylamine, and catalytic activity, was identified as an enzyme-CoA compound. Kinetic constants for CoA transferase are: final specific activity, 110 U/mg of protein corresponding to 1.38 X 10(4) mumol of acrylate activated per mumol of transferase; Km for acrylate, 1.2 X 10(-3) M; Km for acetyl CoA (beta-hydroxypropionyl CoA), 2.4 X 10(-5) M.", "contents": "Purification, new assay, and properties of coenzyme A transferase from Peptostreptococcus elsdenii. Coenzyme A (CoA) transferase from Peptostreptococcus elsdenii has been purified and crystallized, and some of its properties have been established. The work was facilitated by a newly developed coupled and continuous spectrophotometric assay in which the disappearance of added acrylate could be followed at 245 nm. The rate-limiting conversion of acetyl- and beta-hydroxypropionyl CoA to acrylyl CoA by CoA transferase was followed by the non-rate-limiting conversion to beta-hydroxypropionyl CoA by excess crotonase. Thus, a small priming quantity of acetyl CoA served to generate acrylyl CoA, which, by hydration, generated beta-hydroxypropionyl CoA. This product then served to generate more acrylyl CoA in cyclic fashion. The net result was the CoA transferase-limited conversion of acrylate to beta-hydroxypropionate. The purified transferase has a molecular weight of 125,000 and is composed of two subunits of 63,000 each, as determined by disc gel electrophoresis. Short-chain-length monocarboxylic acids are substrates, whereas dicarboxylic or beta-ketocarboxylic acids are not. The reaction kinetics are typical of a ping-pong bi bi mechanism composed of two half reactions linked by a covalent enzyme intermediate. Incubation of the transferase with acetyl CoA in the absence of a fatty acid acceptor yielded a stable intermediate which, by absorption spectrophotometry, radioactivity measurements, reduction with borohydride, reactivity with hydroxylamine, and catalytic activity, was identified as an enzyme-CoA compound. Kinetic constants for CoA transferase are: final specific activity, 110 U/mg of protein corresponding to 1.38 X 10(4) mumol of acrylate activated per mumol of transferase; Km for acrylate, 1.2 X 10(-3) M; Km for acetyl CoA (beta-hydroxypropionyl CoA), 2.4 X 10(-5) M."}
{"id": "PMID:370", "title": "Isolation and purification of Flavobacterium alpha-1,3-glucanase-hydrolyzing, insoluble, sticky glucan of Streptococcus mutans.", "content": "Studies were made on the physical and chemical properties of polysaccharides synthesized by cell-free extracts of Streptococcus mutans, Streptococcus sanguis, and Streptococcus sp. and their susceptibilities to dextranases. Among the polysaccharides examined, insoluble glucans were rather resistant to available dextranase preparations, and the insoluble, sticky glucan produced by S. mutans OMZ 176, which could be important in formation of dental plaques, was the most resistant. By enrichment culture of soil specimens, using OMZ 176 glucans as the sole carbon source, an organism was isolated that produced colonies surrounded by a clear lytic zone on opaque agar plates containing the OMZ 176 glucan. The organism was identified as a strain of Flavobacterium and named the Ek-14 bacterium. EK-14 bacterium was grown in Trypticase soy broth, and an enzyme capable of hydrolyzing the OMZ 176 glucan was concentrated from the culture supernatant and purified by negative adsorption on a diethylaminoethyl-cellulose (DE-32) column and gradient elution chromatography with a carboxymethyl-cellulose (CM-32) column. The enzyme was a basic protein with an isoelectric point of pH 8.5 and molecular weight of 65,000. Its optimum pH was 6.3 and its optimal temperature was 42 C. The purified enzyme released 11% of the total glucose residues of the OMZ 176 glucan as reducing sugars and solubilized about half of the substrate glucan. The products were found to be isomaltose, nigerose, and nigerotriose, with some oligosaccharides. The purified enzyme split the alpha-1,3-glucan endolytically and was inactive toward glucans containing alpha-1,6, alpha-1,4, beta-1,3, beta-1,4, and/or beta-1,6 bonds as the main linkages.", "contents": "Isolation and purification of Flavobacterium alpha-1,3-glucanase-hydrolyzing, insoluble, sticky glucan of Streptococcus mutans. Studies were made on the physical and chemical properties of polysaccharides synthesized by cell-free extracts of Streptococcus mutans, Streptococcus sanguis, and Streptococcus sp. and their susceptibilities to dextranases. Among the polysaccharides examined, insoluble glucans were rather resistant to available dextranase preparations, and the insoluble, sticky glucan produced by S. mutans OMZ 176, which could be important in formation of dental plaques, was the most resistant. By enrichment culture of soil specimens, using OMZ 176 glucans as the sole carbon source, an organism was isolated that produced colonies surrounded by a clear lytic zone on opaque agar plates containing the OMZ 176 glucan. The organism was identified as a strain of Flavobacterium and named the Ek-14 bacterium. EK-14 bacterium was grown in Trypticase soy broth, and an enzyme capable of hydrolyzing the OMZ 176 glucan was concentrated from the culture supernatant and purified by negative adsorption on a diethylaminoethyl-cellulose (DE-32) column and gradient elution chromatography with a carboxymethyl-cellulose (CM-32) column. The enzyme was a basic protein with an isoelectric point of pH 8.5 and molecular weight of 65,000. Its optimum pH was 6.3 and its optimal temperature was 42 C. The purified enzyme released 11% of the total glucose residues of the OMZ 176 glucan as reducing sugars and solubilized about half of the substrate glucan. The products were found to be isomaltose, nigerose, and nigerotriose, with some oligosaccharides. The purified enzyme split the alpha-1,3-glucan endolytically and was inactive toward glucans containing alpha-1,6, alpha-1,4, beta-1,3, beta-1,4, and/or beta-1,6 bonds as the main linkages."}
{"id": "PMID:371", "title": "Production, purification, and characterization of an extracellular chitosanase from Streptomyces.", "content": "The synthesis by Streptomyces sp. no. 6 of an extracellular chitosanase was induced by glucosamine. The enzyme was purified to homogeneity by Sephadex G-100, carboxymethyl-cellulose, and diethylaminoethyl-cellulose chromatography. The purified enzyme hydrolyzed chitosan (the beta-1,4-linked polymer of glucosamine) but not chitin nor carboxymethyl-cellulose. The only products of the hydrolysis detectable by paper chromatography were di- and triglucosamine. Sephadex G-100 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the molecular weight of the enzyme was between 29,000 and 26,000. Acid hydrolysates of the enzyme contained no cysteic acid or glucosamine or other carbohydrate. At 25 C, maximum activity was obtained between pH 4.5 and 6.5. The enzymatic hydrolysis of chitosan occurred over a wide range of temperatures and was maximal at 60 C. The rate of the reaction was inhibited by concentrations of soluble chitosan higher than 0.5 g/liter. The apparent Km calculated from a Lineweaver-Burke plot was 0.688 g/liter at pH 5.5. The enzyme prevented spore germination and caused a significant decrease in the turbidity of germinated spore suspensions of the Mucor strains tested. Such a decrease was the result of a partial lysis of the cell wall.", "contents": "Production, purification, and characterization of an extracellular chitosanase from Streptomyces. The synthesis by Streptomyces sp. no. 6 of an extracellular chitosanase was induced by glucosamine. The enzyme was purified to homogeneity by Sephadex G-100, carboxymethyl-cellulose, and diethylaminoethyl-cellulose chromatography. The purified enzyme hydrolyzed chitosan (the beta-1,4-linked polymer of glucosamine) but not chitin nor carboxymethyl-cellulose. The only products of the hydrolysis detectable by paper chromatography were di- and triglucosamine. Sephadex G-100 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the molecular weight of the enzyme was between 29,000 and 26,000. Acid hydrolysates of the enzyme contained no cysteic acid or glucosamine or other carbohydrate. At 25 C, maximum activity was obtained between pH 4.5 and 6.5. The enzymatic hydrolysis of chitosan occurred over a wide range of temperatures and was maximal at 60 C. The rate of the reaction was inhibited by concentrations of soluble chitosan higher than 0.5 g/liter. The apparent Km calculated from a Lineweaver-Burke plot was 0.688 g/liter at pH 5.5. The enzyme prevented spore germination and caused a significant decrease in the turbidity of germinated spore suspensions of the Mucor strains tested. Such a decrease was the result of a partial lysis of the cell wall."}
{"id": "PMID:372", "title": "Simple and sensitive procedure for screening yeast mutants that lyse at nonpermissive temperatures.", "content": "After mutagenesis, surviving yeast cells are grown on plates at 25 C and later exposed to 37 C. The plates are then overlaid with a soft agar containing p-nitrophenylphosphate at pH 9.7. Lysed cells liberate alkaline phosphatase which gives rise to a yellow color on and around colonies.", "contents": "Simple and sensitive procedure for screening yeast mutants that lyse at nonpermissive temperatures. After mutagenesis, surviving yeast cells are grown on plates at 25 C and later exposed to 37 C. The plates are then overlaid with a soft agar containing p-nitrophenylphosphate at pH 9.7. Lysed cells liberate alkaline phosphatase which gives rise to a yellow color on and around colonies."}
{"id": "PMID:373", "title": "A nucleoside triphosphate-dependent deoxyribonuclease from Bacillus laterosporus. Purification and characterization of the enzyme.", "content": "A deoxyribonuclease, which requires nucleoside triphosphate for reaction, has been purified about 150-fold from extracts of Bacillus laterosporus. Potassium phosphate and ethylene glycol stabilize the purified enzyme. The enzyme degrades double-stranded DNA about 100 times faster than heat-denatured DNA in the presence of nucleoside triphosphate. Double-stranded DNA is not degraded to any measurable extent in the absence of ATP, but the enzyme exhibits activity toward denatured DNA in the absence of nucleoside triphosphate, and this activity seems to be an intrinsic property of this enzyme protein. The optimum pH is 8.5 and the maximum activity is obtained in the copresence of Mg2+ (8.0 X 10(-3)M) and Mn2+ (7.0 X 10(-5)M). ATP and dATP are most effective and nucleoside di- or monophosphates are ineffective. ATP is converted to ADP and inorganic phosphate during the reaction and the ratio of the amount of ATP cleaved to that of hydrolyzed phosphodiester bonds of DNA is about 3:1. An inhibitor of the enzyme was observed in bacterial extracts prepared by sonic disruption; the inhibitory substance is produced in the bacteria in the later stages of cell growth. Preliminary results show that the inhibitor emerged near the void volume of a Sephadex G-200 column, and was relatively heat-stable, RNase-resistant, and DNase-sensitive.", "contents": "A nucleoside triphosphate-dependent deoxyribonuclease from Bacillus laterosporus. Purification and characterization of the enzyme. A deoxyribonuclease, which requires nucleoside triphosphate for reaction, has been purified about 150-fold from extracts of Bacillus laterosporus. Potassium phosphate and ethylene glycol stabilize the purified enzyme. The enzyme degrades double-stranded DNA about 100 times faster than heat-denatured DNA in the presence of nucleoside triphosphate. Double-stranded DNA is not degraded to any measurable extent in the absence of ATP, but the enzyme exhibits activity toward denatured DNA in the absence of nucleoside triphosphate, and this activity seems to be an intrinsic property of this enzyme protein. The optimum pH is 8.5 and the maximum activity is obtained in the copresence of Mg2+ (8.0 X 10(-3)M) and Mn2+ (7.0 X 10(-5)M). ATP and dATP are most effective and nucleoside di- or monophosphates are ineffective. ATP is converted to ADP and inorganic phosphate during the reaction and the ratio of the amount of ATP cleaved to that of hydrolyzed phosphodiester bonds of DNA is about 3:1. An inhibitor of the enzyme was observed in bacterial extracts prepared by sonic disruption; the inhibitory substance is produced in the bacteria in the later stages of cell growth. Preliminary results show that the inhibitor emerged near the void volume of a Sephadex G-200 column, and was relatively heat-stable, RNase-resistant, and DNase-sensitive."}
{"id": "PMID:374", "title": "Rapid radioimmunoassay for guanosine 3',5'-cyclic monophosphate using tritiated ligand.", "content": "A radioimmunoassay procedure for guanosine 3',5'-cyclic monophosphate (CGMP) is described. The procedure is based on competitive binding between [3H]CGMP and non-radioactive CGMP, with separation of bound and unbound CGMP by Millipore filtration. The binding reaction showed very high specificity to CGMP, had a broad pH optimum, and reached equilibrium within a short time. A simple procedure for the pruification of assay samples using Dowex AG 50W-X2 resin is also described. CGMP contents in urine samples were assayed without purification. Injection of glucagon into healthy human volunteers resulted in a small but significant reduction in urinary CGMP level, whereas CAMP excretion increased dramatically.", "contents": "Rapid radioimmunoassay for guanosine 3',5'-cyclic monophosphate using tritiated ligand. A radioimmunoassay procedure for guanosine 3',5'-cyclic monophosphate (CGMP) is described. The procedure is based on competitive binding between [3H]CGMP and non-radioactive CGMP, with separation of bound and unbound CGMP by Millipore filtration. The binding reaction showed very high specificity to CGMP, had a broad pH optimum, and reached equilibrium within a short time. A simple procedure for the pruification of assay samples using Dowex AG 50W-X2 resin is also described. CGMP contents in urine samples were assayed without purification. Injection of glucagon into healthy human volunteers resulted in a small but significant reduction in urinary CGMP level, whereas CAMP excretion increased dramatically."}
{"id": "PMID:375", "title": "The effect of tryptophan administration on fatty acid synthesis in the livers of rats under various nutritional conditions.", "content": "1. Tryptophan was administered to rats under various nutritional conditions: fasted for 24 hr, fasted and refed with glucose or corn-oil, fasted and administered glycerol intramuscularly, and nonfasted. 2. The changes in the contents of glycolytic intermediates in the livers indicated that the phosphoenolpyruvate carboxykinase [EC 4.1.1.32] reaction is inhibited by tryptophan administration in all groups of rats. The inversely related changes in the contents of malate and phosphoenolpyruvate were associated with the accumulation of quinolinate in the livers. The content of quinolinate which exhibited the half-maximal effect on the contents of both metabolites was 0.1-0.2 mumole per g liver. 3. The rate of incorporation of 3H from 3H2O into the total hepatic fatty acids was increased about 2-fold by the administration of this amino acid to the fasted rats. The enhancement of the rate was closely related to the increase in the citrate content. The hyperlipogenesis was also related to the decrease of acetyl-CoA and the increase of malonyl-CoA. The content of long-chain acyl-CoA was not affected. These effects of tryptophan administration on the hepatic fatty acid metabolism were found in all groups of rats. The liver content of glycerol 3-phosphate was decreased by tryptophan administration was markedly increased by glycerol injection. The injection of glycerol into the control and the tryptophan-treated rats produced a marked increase of glycerol 3-phosphate but did not affect the rate of fatty acid synthesis in the livers of either group. 4. It may be concluded that, in the livers of rats under various nutritional conditions, the short-term control of fatty acid synthesis by tryptophan administration is most likely due to the activation of acetyl-coenzyme A carboxylase [EC 6.4.1.2] by citrate.", "contents": "The effect of tryptophan administration on fatty acid synthesis in the livers of rats under various nutritional conditions. 1. Tryptophan was administered to rats under various nutritional conditions: fasted for 24 hr, fasted and refed with glucose or corn-oil, fasted and administered glycerol intramuscularly, and nonfasted. 2. The changes in the contents of glycolytic intermediates in the livers indicated that the phosphoenolpyruvate carboxykinase [EC 4.1.1.32] reaction is inhibited by tryptophan administration in all groups of rats. The inversely related changes in the contents of malate and phosphoenolpyruvate were associated with the accumulation of quinolinate in the livers. The content of quinolinate which exhibited the half-maximal effect on the contents of both metabolites was 0.1-0.2 mumole per g liver. 3. The rate of incorporation of 3H from 3H2O into the total hepatic fatty acids was increased about 2-fold by the administration of this amino acid to the fasted rats. The enhancement of the rate was closely related to the increase in the citrate content. The hyperlipogenesis was also related to the decrease of acetyl-CoA and the increase of malonyl-CoA. The content of long-chain acyl-CoA was not affected. These effects of tryptophan administration on the hepatic fatty acid metabolism were found in all groups of rats. The liver content of glycerol 3-phosphate was decreased by tryptophan administration was markedly increased by glycerol injection. The injection of glycerol into the control and the tryptophan-treated rats produced a marked increase of glycerol 3-phosphate but did not affect the rate of fatty acid synthesis in the livers of either group. 4. It may be concluded that, in the livers of rats under various nutritional conditions, the short-term control of fatty acid synthesis by tryptophan administration is most likely due to the activation of acetyl-coenzyme A carboxylase [EC 6.4.1.2] by citrate."}
{"id": "PMID:376", "title": "Electrophoretic investigations of the acid conformational change of alpha-lactalbumin.", "content": "In order to clarify how the electrophoretic behavior reflects the conformational transition of globular proteins, moving boundary electrophoresis was applied to analysis of the acid conformational change of alpha-lactalbumin. The appearance of only a single electrophoretic boundary in the transition region of the protein suggests a very rapid transition with a half-time estimated to be smaller than 7 min on the basis of the theory of isomerizing systems in electrophoresis. The transition is clearly reflected in the dependence of the mobility on the protein net charge, which shows a sigmoidal curve closely similar to that obtained by a Linderstr\u00f8m-Lang pH-tritration plot for the carboxyl groups of alpha-lactalbumin. It was also concluded from the transition curves that the acidfication does not result in complete unfolding, but that a compact structure is maintained in the acidic region with an apparently expanded form as compared to the native state of the protein. All results obtained by electrophoresis were also supported by the results of pH-jump studies, analytical gel chromatography, and CD measurements.", "contents": "Electrophoretic investigations of the acid conformational change of alpha-lactalbumin. In order to clarify how the electrophoretic behavior reflects the conformational transition of globular proteins, moving boundary electrophoresis was applied to analysis of the acid conformational change of alpha-lactalbumin. The appearance of only a single electrophoretic boundary in the transition region of the protein suggests a very rapid transition with a half-time estimated to be smaller than 7 min on the basis of the theory of isomerizing systems in electrophoresis. The transition is clearly reflected in the dependence of the mobility on the protein net charge, which shows a sigmoidal curve closely similar to that obtained by a Linderstr\u00f8m-Lang pH-tritration plot for the carboxyl groups of alpha-lactalbumin. It was also concluded from the transition curves that the acidfication does not result in complete unfolding, but that a compact structure is maintained in the acidic region with an apparently expanded form as compared to the native state of the protein. All results obtained by electrophoresis were also supported by the results of pH-jump studies, analytical gel chromatography, and CD measurements."}
{"id": "PMID:377", "title": "Studies on cathepsins of rat liver lysosomes. II. Comparative studies on multiple forms of cathepsin A.", "content": "The multiple forms of cathepsin A (AI, AII, and AIII) purified from the lysosome fraction of rat liver by Sephadex G-200 and DEAE-Sephadex chromatographies were studied comparatively. Forms AI, AII and AIII were stable between pH 3.0 and 5.5, and had pH optima for CBZ-Glu-Phe at 5.6, 5.8, and 5.9, respectively. These activities were rapidly lost on heating above 60 degrees. Their isoelectric points were at 4.7, 4.8, and 4.9, and the Michaelis constants for CBZ-Glu-Phe were calculated as 10, 6.6, and 4.2 X 10(-4)M, respectively. Activity was inhibited by Ag+, Au3+, Hg2+, iodine, and p-chloromercuribenzoate (PCMB). Diisopropyl fluorophosphate (DFP), phenylmethanesulfonyl fluoride (PMSF), toluenesuffonyl fluoride (TSF), and sodium dodecyl sulfate (SDS) were inhibitory at a concentration of 10(-3)M. Soybean trypsin inhibitor, pepstatin, leupeptins, and antipain were not inhibitory, while chymostatin caused slight inhibition. No distinct difference was observed in the effects of these compounds on the multiple forms of cathepsin A despite differences in the molecular weights of these forms (100,000, 200,000, and 420,000, respectively). In immuno-diffusion analysis, cathepsin AI, AII, and AIII which had been treated with EDTA, dithiothreitol, PCMB, and a high concentration of NaCl, gave the same precipitin patterns as the untreated enzymes, but treatment with 6 M urea caused a slight alteration of the pattern. After SDS-treatment (50 mM or more), the precipitin lines of these multiple forms fused and gave a single, identical line. This suggests that the different forms of the cathepsin A are all composed of subunits which are immunologically identical or closely related, and that the subunits are mainly bound by hydrophobic forces. This conclusion is supported by results obtained by poliacrylamide gel electrophoresis in the presence of SDS.", "contents": "Studies on cathepsins of rat liver lysosomes. II. Comparative studies on multiple forms of cathepsin A. The multiple forms of cathepsin A (AI, AII, and AIII) purified from the lysosome fraction of rat liver by Sephadex G-200 and DEAE-Sephadex chromatographies were studied comparatively. Forms AI, AII and AIII were stable between pH 3.0 and 5.5, and had pH optima for CBZ-Glu-Phe at 5.6, 5.8, and 5.9, respectively. These activities were rapidly lost on heating above 60 degrees. Their isoelectric points were at 4.7, 4.8, and 4.9, and the Michaelis constants for CBZ-Glu-Phe were calculated as 10, 6.6, and 4.2 X 10(-4)M, respectively. Activity was inhibited by Ag+, Au3+, Hg2+, iodine, and p-chloromercuribenzoate (PCMB). Diisopropyl fluorophosphate (DFP), phenylmethanesulfonyl fluoride (PMSF), toluenesuffonyl fluoride (TSF), and sodium dodecyl sulfate (SDS) were inhibitory at a concentration of 10(-3)M. Soybean trypsin inhibitor, pepstatin, leupeptins, and antipain were not inhibitory, while chymostatin caused slight inhibition. No distinct difference was observed in the effects of these compounds on the multiple forms of cathepsin A despite differences in the molecular weights of these forms (100,000, 200,000, and 420,000, respectively). In immuno-diffusion analysis, cathepsin AI, AII, and AIII which had been treated with EDTA, dithiothreitol, PCMB, and a high concentration of NaCl, gave the same precipitin patterns as the untreated enzymes, but treatment with 6 M urea caused a slight alteration of the pattern. After SDS-treatment (50 mM or more), the precipitin lines of these multiple forms fused and gave a single, identical line. This suggests that the different forms of the cathepsin A are all composed of subunits which are immunologically identical or closely related, and that the subunits are mainly bound by hydrophobic forces. This conclusion is supported by results obtained by poliacrylamide gel electrophoresis in the presence of SDS."}
{"id": "PMID:378", "title": "Recombination of ciliary dynein of Tetrahymena with the outer fibers.", "content": "Recombination of ciliary dyneins of Tetrahymena pyriformis with the outer fibers was investigated using turbidimetry, co-sedimentation analysis and electron microscopy. As reported by Gibbons, 30S dynein could recombine with the outer fibers, while 14S dynein did to so a lesser extent. At acidic pH, however, most of the 14S dynein was also rebound to the outer fibers. When an excess of crude dynein fraction was added to the outer fiber fraction at pH 8.2, electron microscopic observations showed that the outer doublet microtubules were decorated not only with arms but also with other electron-dense materials. On the other hand, when crude dynein fraction was mixed with the outer fibers in an appropriate quantity, only arms were reconstituted at the regular positions of A-subfibers. ATP had an inhibitory effect on the recombination of dynein with the outer fibers.", "contents": "Recombination of ciliary dynein of Tetrahymena with the outer fibers. Recombination of ciliary dyneins of Tetrahymena pyriformis with the outer fibers was investigated using turbidimetry, co-sedimentation analysis and electron microscopy. As reported by Gibbons, 30S dynein could recombine with the outer fibers, while 14S dynein did to so a lesser extent. At acidic pH, however, most of the 14S dynein was also rebound to the outer fibers. When an excess of crude dynein fraction was added to the outer fiber fraction at pH 8.2, electron microscopic observations showed that the outer doublet microtubules were decorated not only with arms but also with other electron-dense materials. On the other hand, when crude dynein fraction was mixed with the outer fibers in an appropriate quantity, only arms were reconstituted at the regular positions of A-subfibers. ATP had an inhibitory effect on the recombination of dynein with the outer fibers."}
{"id": "PMID:379", "title": "Affinity labeling of D-amino acid oxidase with an acetylenic substrate.", "content": "The acetylenic substrate, D-2-amino-4-pentynoic acid (D-propargylglycine), was oxidatively deaminated by hog kidney D-amino acid oxidase[EC 1.4.3.3], with accompanying inactivation of the enzyme. The flavin which was extracted by hot methanol from the inactivated enzyme was identical with authentic FAD by thin-layer chromatography and circular dichroism. The excitation spectrum of emission at 520 nm of the released flavin was very similar to the absorption spectrum of oxidized FAD. The released flavin was reduced by potassium borohydride. The apoenzyme prepared after propargylglycine treatment did not show restored D-amino acid oxidase activity on adding exogenous FAD. The absorption spectrum of this inactivated apoenzyme showed absorption peaks at 279 and 317 nm, and a shoulder at about 290 nm. These results strongly indicate that the inactivation reaction is a dynamic affinity labeling with D-propargylglycine which produces irreversible inactivation of the enzyme by a covalent modification of an amino acid residue at the active site.", "contents": "Affinity labeling of D-amino acid oxidase with an acetylenic substrate. The acetylenic substrate, D-2-amino-4-pentynoic acid (D-propargylglycine), was oxidatively deaminated by hog kidney D-amino acid oxidase[EC 1.4.3.3], with accompanying inactivation of the enzyme. The flavin which was extracted by hot methanol from the inactivated enzyme was identical with authentic FAD by thin-layer chromatography and circular dichroism. The excitation spectrum of emission at 520 nm of the released flavin was very similar to the absorption spectrum of oxidized FAD. The released flavin was reduced by potassium borohydride. The apoenzyme prepared after propargylglycine treatment did not show restored D-amino acid oxidase activity on adding exogenous FAD. The absorption spectrum of this inactivated apoenzyme showed absorption peaks at 279 and 317 nm, and a shoulder at about 290 nm. These results strongly indicate that the inactivation reaction is a dynamic affinity labeling with D-propargylglycine which produces irreversible inactivation of the enzyme by a covalent modification of an amino acid residue at the active site."}
{"id": "PMID:380", "title": "Studies on trypsin inhibitor in barley. I. Purification and some properties.", "content": "To clarify the properties and functions of a trypsin inhibitor from Japanese barley in comparison with the inhibitor from Pirkka barley, an inhibitor was isolated from  the barley Hordeum distichum L var. emend Lamark by extraction with 1% NaCl, ammonium sulfate fractionation and repeated chromatography on DEAE-cellulose and CM-cellulose. The final purified preparation of the inhibitor was found to be homogeneous by both chromatographic and electrophoretic analysis. The inhibitor was thermostable and was stable over the broad pH range from 2 to 11. No inhibition was observed by heavy metal ions and many reagents at 10(-2) M, except that p-chloromercuribenzoate caused a 69% loss of activity. The inhibitor was subjected to isoelectric focusing at pH 7.51 and its molecular weight was calculated to be 14,200+/-900 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The apparent dissociation constant for the complex between the inhibitor and trypsin[EC 3.4.21.4] was 1.64 X 10(-7)M with casein as a substrate. One microgram of purified inhibitor inhibited 1.5 mug of pure trypsin in the hydrolysis of alpha-N-benzoyl-DL-arginine-p-nitroanilide. By chemical modification of arginyl residues in the inhibitor with 1,2-cyclohexanedione, the inhibitor was shown to be an arginine inhibitor. The inhibitor contained relatively many basic amino acids and few half cystines as compared with Pirkka barley trypsin inhibitor.", "contents": "Studies on trypsin inhibitor in barley. I. Purification and some properties. To clarify the properties and functions of a trypsin inhibitor from Japanese barley in comparison with the inhibitor from Pirkka barley, an inhibitor was isolated from  the barley Hordeum distichum L var. emend Lamark by extraction with 1% NaCl, ammonium sulfate fractionation and repeated chromatography on DEAE-cellulose and CM-cellulose. The final purified preparation of the inhibitor was found to be homogeneous by both chromatographic and electrophoretic analysis. The inhibitor was thermostable and was stable over the broad pH range from 2 to 11. No inhibition was observed by heavy metal ions and many reagents at 10(-2) M, except that p-chloromercuribenzoate caused a 69% loss of activity. The inhibitor was subjected to isoelectric focusing at pH 7.51 and its molecular weight was calculated to be 14,200+/-900 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The apparent dissociation constant for the complex between the inhibitor and trypsin[EC 3.4.21.4] was 1.64 X 10(-7)M with casein as a substrate. One microgram of purified inhibitor inhibited 1.5 mug of pure trypsin in the hydrolysis of alpha-N-benzoyl-DL-arginine-p-nitroanilide. By chemical modification of arginyl residues in the inhibitor with 1,2-cyclohexanedione, the inhibitor was shown to be an arginine inhibitor. The inhibitor contained relatively many basic amino acids and few half cystines as compared with Pirkka barley trypsin inhibitor."}
{"id": "PMID:381", "title": "Metabolism of dog gastric mucosa. Nucleotide levels in parietal cells.", "content": "Adenine and pyridine nucleotide levels as well as those of phosphate, phosphocreatine, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, glucose, and glycogen were measured in histologically defined parietal and mucous cell sections of biopsies of dog gastric mucosa at rest, and in various secretory states. As a result of stimulation of secretion, there appeared to be no change in adenine nucleotide levels, or phosphocreatine, but there was a rise in inorganic phosphate and a fall in phosphorylation potential. However, there was a marked increase in NADH, but no change in NADPH with onset of acid secretion. The increase in the lactate to pyruvate ratio showed that the increased NADH level occurred in the cytoplasm and these data are discussed with reference to change in cell pH.", "contents": "Metabolism of dog gastric mucosa. Nucleotide levels in parietal cells. Adenine and pyridine nucleotide levels as well as those of phosphate, phosphocreatine, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, glucose, and glycogen were measured in histologically defined parietal and mucous cell sections of biopsies of dog gastric mucosa at rest, and in various secretory states. As a result of stimulation of secretion, there appeared to be no change in adenine nucleotide levels, or phosphocreatine, but there was a rise in inorganic phosphate and a fall in phosphorylation potential. However, there was a marked increase in NADH, but no change in NADPH with onset of acid secretion. The increase in the lactate to pyruvate ratio showed that the increased NADH level occurred in the cytoplasm and these data are discussed with reference to change in cell pH."}
{"id": "PMID:382", "title": "Metal ion dependence of the binding of triiodothyronine by cytosol proteins of bullfrog tadpole tissues.", "content": "The binding of triiodothyronine by Rana catesbeiana tadpole tail fin, tail muscle, kidney, and liver cytosol was studied using dextran-coated charcoal to separate bound and free hormone. A metal ion dependency was suggested by the fact that EDTA decreased the binding of triiodothyronine 80 to 90% in tail fin and tail muscle cytosol. Inhibition of binding in kidney or liver was less, 40 to 50%. This inhibition could be restored by adding an excess of divalent cations with an order of potency of Mn2+ greater than Ca2+ congruent to Co2+ greater than Sr2+ greater than Ba2+ greater than Mg2+. Other chelators, e.g. o-phenanthroline, 8-hydroxyquinoline, and ethylene glycol bis(beta-aminoethylether)-N,N'-tetraacetate also decreased the binding of triiodothyronine, whereas citrate, oxalate, imidazole, and glycine had no effect. The triiodothyronine binding capacity of tail fin cytosol was reduced by EDTA treatment and dialysis against buffer. Ca2+ in the 1 to 10 mM range and Mn2+ at 1 mM could restore the binding to normal levels. Higher Mn2+ increased binding 70% above normal or to Ca2+-restored levels. The triiodothyronine cytosol binding activity was nondialyzable, heat-labile. pH-dependent, pronase-digestible, but unaffected by incubation with trypsin, RNase, and DNase, suggesting that the cytosol binding sites are acidic proteins. Scatchard analysis of triiodothyronine binding by the cytosol of different tissues, revealed Kassoc of 7.1 x 10(6) M(-1), 11.6 x 10(6) M(-1), 3.6 X 10(6) M(-1), and 68.0 x 10(6) M(-1) for tail fin, tail muscle, kidney, and liver cytosol, respectively. The corresponding maximal binding capacities in picomoles per mg of crude cytosol protein in these four tissues were 10.4, 0.86, 1.3, and 0.04, respectively.", "contents": "Metal ion dependence of the binding of triiodothyronine by cytosol proteins of bullfrog tadpole tissues. The binding of triiodothyronine by Rana catesbeiana tadpole tail fin, tail muscle, kidney, and liver cytosol was studied using dextran-coated charcoal to separate bound and free hormone. A metal ion dependency was suggested by the fact that EDTA decreased the binding of triiodothyronine 80 to 90% in tail fin and tail muscle cytosol. Inhibition of binding in kidney or liver was less, 40 to 50%. This inhibition could be restored by adding an excess of divalent cations with an order of potency of Mn2+ greater than Ca2+ congruent to Co2+ greater than Sr2+ greater than Ba2+ greater than Mg2+. Other chelators, e.g. o-phenanthroline, 8-hydroxyquinoline, and ethylene glycol bis(beta-aminoethylether)-N,N'-tetraacetate also decreased the binding of triiodothyronine, whereas citrate, oxalate, imidazole, and glycine had no effect. The triiodothyronine binding capacity of tail fin cytosol was reduced by EDTA treatment and dialysis against buffer. Ca2+ in the 1 to 10 mM range and Mn2+ at 1 mM could restore the binding to normal levels. Higher Mn2+ increased binding 70% above normal or to Ca2+-restored levels. The triiodothyronine cytosol binding activity was nondialyzable, heat-labile. pH-dependent, pronase-digestible, but unaffected by incubation with trypsin, RNase, and DNase, suggesting that the cytosol binding sites are acidic proteins. Scatchard analysis of triiodothyronine binding by the cytosol of different tissues, revealed Kassoc of 7.1 x 10(6) M(-1), 11.6 x 10(6) M(-1), 3.6 X 10(6) M(-1), and 68.0 x 10(6) M(-1) for tail fin, tail muscle, kidney, and liver cytosol, respectively. The corresponding maximal binding capacities in picomoles per mg of crude cytosol protein in these four tissues were 10.4, 0.86, 1.3, and 0.04, respectively."}
{"id": "PMID:383", "title": "The active form of cytochrome P-450 from bovine adrenocortical mitochondria.", "content": "Cytochrome P-450 from bovine adrenocortical mitochondria exists in three forms of molecular weight: 850,000 (protein 16), of one-half (protein 8), and of one-quarter of this value (protein 4). The forms of the enzyme are named according to the number of subunits and all appear to be active in converting cholesterol to 3beta-hydroxy-5-pregnen-20-one (side chain cleavage) (Shikita, M., and Hall, P.F. (1973) J. Biol. Chem. 248, 5606). To determine whether all three forms are active at their characteristic molecular weights, the three cytochromes were each layered onto separate sucrose density gradients and centrifuged at 49,000 rpm for 60 min; the gradients contained all the factors necessary for side chain cleavage including one of the following substrates: cholesterol, 20S-hydroxycholesterol, and 20S,22R-dihydroxycholesterol. Regardless of the form of P-450 layered onto the gradient and regardless of the substrate, enzyme activity (side chain cleavage) was observed only in fractions corresponding to a sedimentation coefficient of 20 to 22 S which is that for protein 16. No activity was observed at S values corresponding to either protein 8 or protein 4. These findings indicate that the active form of cytochrome P-450 from adrenocortical mitochondria is that containing 16 subunits, i.e. the form in which the cytochrome is normally isolated from adrenal mitochondria. Forms consisting of eight and four subunits which can be prepared from protein 16 become active only by forming protein 16, at least in an aqueous medium in vitro.", "contents": "The active form of cytochrome P-450 from bovine adrenocortical mitochondria. Cytochrome P-450 from bovine adrenocortical mitochondria exists in three forms of molecular weight: 850,000 (protein 16), of one-half (protein 8), and of one-quarter of this value (protein 4). The forms of the enzyme are named according to the number of subunits and all appear to be active in converting cholesterol to 3beta-hydroxy-5-pregnen-20-one (side chain cleavage) (Shikita, M., and Hall, P.F. (1973) J. Biol. Chem. 248, 5606). To determine whether all three forms are active at their characteristic molecular weights, the three cytochromes were each layered onto separate sucrose density gradients and centrifuged at 49,000 rpm for 60 min; the gradients contained all the factors necessary for side chain cleavage including one of the following substrates: cholesterol, 20S-hydroxycholesterol, and 20S,22R-dihydroxycholesterol. Regardless of the form of P-450 layered onto the gradient and regardless of the substrate, enzyme activity (side chain cleavage) was observed only in fractions corresponding to a sedimentation coefficient of 20 to 22 S which is that for protein 16. No activity was observed at S values corresponding to either protein 8 or protein 4. These findings indicate that the active form of cytochrome P-450 from adrenocortical mitochondria is that containing 16 subunits, i.e. the form in which the cytochrome is normally isolated from adrenal mitochondria. Forms consisting of eight and four subunits which can be prepared from protein 16 become active only by forming protein 16, at least in an aqueous medium in vitro."}
{"id": "PMID:384", "title": "Effects of strong electrolyte upon the activity of Clostridium perfringens sialidase toward sialyllactose and sialoglycolipids.", "content": "Clostridium perfringens sialidase was purified by affinity chromatography. Kinetic properties of the enzyme were examined with sialyllactose and with mixed sialoglycolipids (gangliosides) as substrates. With the latter substrate in 0.01 M Tris-acete in the absence of strong electrolyte, the pH optimum for enzymatic activity was 6.8. Addition of strong electrolyte (0.01 to 0.10 M Nac1) to the reaction medium caused an acidic shift and a broadening of the pH optimum, Enzymatic activity at pH 5.8 rose approximately 2.5-fold; a concomitant loss of activity at pH 6.8 was also observed. The alteration of enzymatic activity caused by strong electrolyte were dependent upon changes in Vmax. Km remained nearly invariant. Thus, a reversible transition of the enzyme from a relatively inactive to a highly active form occurred as a function of strong electrolyte concentration. Determination of the pK values of the active functional groups of C. perfringens sialidase revealed that the effects of strong electrolyte were exerted upon the pKa group of the enzyme. Strong electrolyte appeared to shield unfavorable electrostatic interactions between polyanionic sialoglycolipid micelles and the enzyme molecule, thus protecting the pKa group from inactivation. In comparision with the effects of strong electrolyte upon enzymatic activity toward the sialoglycolipid substrate, those observed with the monovalent substrate, sialyllacthose, were minor. Collectively, these findings indicate that ionic environment may effectively control the activity and relative substrate specificity of C. perfringens sialidase at a given pH. Furthermore, they explain the low pH optima and skewed pH profiles previously reported for enzymatic activity toward high molecular weight substrates.", "contents": "Effects of strong electrolyte upon the activity of Clostridium perfringens sialidase toward sialyllactose and sialoglycolipids. Clostridium perfringens sialidase was purified by affinity chromatography. Kinetic properties of the enzyme were examined with sialyllactose and with mixed sialoglycolipids (gangliosides) as substrates. With the latter substrate in 0.01 M Tris-acete in the absence of strong electrolyte, the pH optimum for enzymatic activity was 6.8. Addition of strong electrolyte (0.01 to 0.10 M Nac1) to the reaction medium caused an acidic shift and a broadening of the pH optimum, Enzymatic activity at pH 5.8 rose approximately 2.5-fold; a concomitant loss of activity at pH 6.8 was also observed. The alteration of enzymatic activity caused by strong electrolyte were dependent upon changes in Vmax. Km remained nearly invariant. Thus, a reversible transition of the enzyme from a relatively inactive to a highly active form occurred as a function of strong electrolyte concentration. Determination of the pK values of the active functional groups of C. perfringens sialidase revealed that the effects of strong electrolyte were exerted upon the pKa group of the enzyme. Strong electrolyte appeared to shield unfavorable electrostatic interactions between polyanionic sialoglycolipid micelles and the enzyme molecule, thus protecting the pKa group from inactivation. In comparision with the effects of strong electrolyte upon enzymatic activity toward the sialoglycolipid substrate, those observed with the monovalent substrate, sialyllacthose, were minor. Collectively, these findings indicate that ionic environment may effectively control the activity and relative substrate specificity of C. perfringens sialidase at a given pH. Furthermore, they explain the low pH optima and skewed pH profiles previously reported for enzymatic activity toward high molecular weight substrates."}
{"id": "PMID:385", "title": "Reconstitution of ion transport and respiratory control in vesicles formed from reduced coenzyme Q-cytochrome c reductase and phospholipids.", "content": "Reduced coenzyme Q-cytochrome c reductase from bovine heart mitochondria (complex III) was incorporated into phospholipid vesicles by the cholate dialysis procedure. Soybean phospholipids or mixtures of purified phosphatidylcholine, phosphatidylethanolamine, and cardiolipin could be used. Oxidation of reduced coenzyme Q2 by the reconstituted vesicles with cytochrome c as oxidant showed the following energy-coupling phenomena. 1. Protons were translocated outward with a coupling ratio, H+/2e, of 1.9 +/- 0.2. Measurements with mitochondria under similar conditions showed an H+/2e ratio of 1.8. Proton translocation was not seen in the presence of uncoupling agents and was in addition to the net acidification of the medium from the over-all oxidation reaction. 2. Potassium ions were taken up by the reconstituted vesicles in the presence of valinomycin in a reaction coupled to electron transfer. The coupling ratio for K+ uptake, K+/2e, was 2.0 in the vesicles and approximately 1.5 in mitochondria. 3. The rate of oxidation of reduced coenzyme Q2 by the reconstituted vesicles was stimulated up to 10-fold by uncouplers or by valinomycin plus nigericin and K+ ions. Addition of valinomycin alone in a K+ medium caused a transient stimulation of electron transfer. The results indicate that energy coupling can be observed with isolated reduced coenzyme Q-cytochrome c reductase if the enzyme complex is properly incorporated into a phospholipid vesicle.", "contents": "Reconstitution of ion transport and respiratory control in vesicles formed from reduced coenzyme Q-cytochrome c reductase and phospholipids. Reduced coenzyme Q-cytochrome c reductase from bovine heart mitochondria (complex III) was incorporated into phospholipid vesicles by the cholate dialysis procedure. Soybean phospholipids or mixtures of purified phosphatidylcholine, phosphatidylethanolamine, and cardiolipin could be used. Oxidation of reduced coenzyme Q2 by the reconstituted vesicles with cytochrome c as oxidant showed the following energy-coupling phenomena. 1. Protons were translocated outward with a coupling ratio, H+/2e, of 1.9 +/- 0.2. Measurements with mitochondria under similar conditions showed an H+/2e ratio of 1.8. Proton translocation was not seen in the presence of uncoupling agents and was in addition to the net acidification of the medium from the over-all oxidation reaction. 2. Potassium ions were taken up by the reconstituted vesicles in the presence of valinomycin in a reaction coupled to electron transfer. The coupling ratio for K+ uptake, K+/2e, was 2.0 in the vesicles and approximately 1.5 in mitochondria. 3. The rate of oxidation of reduced coenzyme Q2 by the reconstituted vesicles was stimulated up to 10-fold by uncouplers or by valinomycin plus nigericin and K+ ions. Addition of valinomycin alone in a K+ medium caused a transient stimulation of electron transfer. The results indicate that energy coupling can be observed with isolated reduced coenzyme Q-cytochrome c reductase if the enzyme complex is properly incorporated into a phospholipid vesicle."}
{"id": "PMID:387", "title": "sn-Glycerol-3-phosphate acyltransferase activity in particulate preparations from anaerobic, light-grown cells of Rhodopseudomonas spheroides. Involvement of acyl thiolester derivatives of acyl carrier protein in the synthesis of complex lipids.", "content": "Crude particulate preparations obtained from anaerobic, light-grown cells of Rhodopseudomonas spheroides have been shown to possess a significant level of sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) activity. In contrast to the enzyme from Escherichia coli, the R. spheroides glycerophosphate acyltransferase has a high specificity for acyl thiolester derivatives of acyl carrier protein (ACP) as acyl donors for the reaction. Only limited , nonlinear glycerophosphate incorporation into lipid occurs when acyl coenzyme A (CoA) derivatives are employed as acyl substrate. With oleyl-ACP as substrate, maximal enzyme activity was observed at 40 degrees, over a broad pH range (6.0 to 8.5) and did not require a divalent metal cation. The presence of dithiothreitol stimulated enzyme-activity 15 to 20%. When oleyl-ACP or palmityl-ACP was employed as sole acyl group donor, the major products recoverable from the reaction mixtures were lysophosphatidic acid, phosphatidic acid, and monoglyceride. Althouh oleyl-ACP and palmityl-ACP gave comparable maximal velocities in the initial acylation of glycerophosphate, the formation of phosphatidic acid occurred preferentially with the unsaturated acyl-ACP derivative.", "contents": "sn-Glycerol-3-phosphate acyltransferase activity in particulate preparations from anaerobic, light-grown cells of Rhodopseudomonas spheroides. Involvement of acyl thiolester derivatives of acyl carrier protein in the synthesis of complex lipids. Crude particulate preparations obtained from anaerobic, light-grown cells of Rhodopseudomonas spheroides have been shown to possess a significant level of sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) activity. In contrast to the enzyme from Escherichia coli, the R. spheroides glycerophosphate acyltransferase has a high specificity for acyl thiolester derivatives of acyl carrier protein (ACP) as acyl donors for the reaction. Only limited , nonlinear glycerophosphate incorporation into lipid occurs when acyl coenzyme A (CoA) derivatives are employed as acyl substrate. With oleyl-ACP as substrate, maximal enzyme activity was observed at 40 degrees, over a broad pH range (6.0 to 8.5) and did not require a divalent metal cation. The presence of dithiothreitol stimulated enzyme-activity 15 to 20%. When oleyl-ACP or palmityl-ACP was employed as sole acyl group donor, the major products recoverable from the reaction mixtures were lysophosphatidic acid, phosphatidic acid, and monoglyceride. Althouh oleyl-ACP and palmityl-ACP gave comparable maximal velocities in the initial acylation of glycerophosphate, the formation of phosphatidic acid occurred preferentially with the unsaturated acyl-ACP derivative."}
{"id": "PMID:386", "title": "Ion transport and respiratory control in vesicles formed from reduced nicotinamide adenine dinucleotide coenzyme Q reductase and phospholipids.", "content": "NADH-coenzyme Q reductase from bovine heart mitochondria (complex I) was incorporated into phospholipid vesicles by the cholate dialysis procedure. Mixtures of purified phosphatidylcholine and phosphatidylethanolamine were required. Oxidation of NADH by coenzyme Q1 catalyzed by the reconstituted vesicles was coupled to proton translocation, directed inward, with an H+/2e ratio greater than 1.4. Similar experiments measuring proton translocation in submitochondrial particles gave an H+/2e ratio of 1.8. The proton translocation in both systems was not seen in the presence of uncoupling agents and was in addition to the net proton uptake from the reduction of coenzyme Q1 by NADH. Electron transfer in the reconstituted vesicles also caused the uptake of the permeant anion tetraphenylboron. The rate of electron transfer by the reconstituted vesicles was stimulated about 3-fold by uncouplers or by valinomycin plus nigericin and K+ ions. The results indicate that energy coupling can be observed with isolated NADH-coenzyme Q reductase if the enzyme complex is properly incorporated into a phospholipid vesicle.", "contents": "Ion transport and respiratory control in vesicles formed from reduced nicotinamide adenine dinucleotide coenzyme Q reductase and phospholipids. NADH-coenzyme Q reductase from bovine heart mitochondria (complex I) was incorporated into phospholipid vesicles by the cholate dialysis procedure. Mixtures of purified phosphatidylcholine and phosphatidylethanolamine were required. Oxidation of NADH by coenzyme Q1 catalyzed by the reconstituted vesicles was coupled to proton translocation, directed inward, with an H+/2e ratio greater than 1.4. Similar experiments measuring proton translocation in submitochondrial particles gave an H+/2e ratio of 1.8. The proton translocation in both systems was not seen in the presence of uncoupling agents and was in addition to the net proton uptake from the reduction of coenzyme Q1 by NADH. Electron transfer in the reconstituted vesicles also caused the uptake of the permeant anion tetraphenylboron. The rate of electron transfer by the reconstituted vesicles was stimulated about 3-fold by uncouplers or by valinomycin plus nigericin and K+ ions. The results indicate that energy coupling can be observed with isolated NADH-coenzyme Q reductase if the enzyme complex is properly incorporated into a phospholipid vesicle."}
{"id": "PMID:388", "title": "Studies on thyroid hormone-binding proteins. I. The subunit structure of human thyroxine-binding globulin and its interaction with ligands.", "content": "Thyroxine-binding globulin was isolated from human plasma by ammonium sulfate fractionation, chromatographic separations on diethylaminoethyl-Sephadex, gel chromatography, and two different electrophoretic procedures. The highly purified was homogeneous when subjected to polyacrylamide gel electrophoresis, ultracentrifugation analyses, and immunochemical determinations. The weight average molecular weight as determined by sedimentation equilibrium ultracentrifugations was 54,000 and by sedimentation diffusion data 55,000. Amino acid analyses indicated a minimum of 110 amino acid residues per molecule. By determination of the minimum in the curve for the fraction of maximum deviation from the amino acid analyses it was found that the minimum molecular weight for the polypeptide was 12,200. Carbohydrate analyses demonstrated the presence f equimolar amounts of amnnose, galactose, and glucosamine, and the carbohydrate portion constituted 7.5% of the total weight. The amino acid analyses suggested that thyroxine-binding globulin is composed of 4 subunits. Molecular weight determinations by gel chromatography in 6 M guanidine hydrochloride indicated the presence of three species of globulin with apparent molecular weights 52,000, 25,000, and 13,500, respectively. Prolonged storage in guanidine hydrochloride promoted a more than 60% yield of the monomeric species. Moreover, a half-molecule of thyroxine-binding globulin was isolated and shown to consist of two polypeptide chains of similar molecular weight...", "contents": "Studies on thyroid hormone-binding proteins. I. The subunit structure of human thyroxine-binding globulin and its interaction with ligands. Thyroxine-binding globulin was isolated from human plasma by ammonium sulfate fractionation, chromatographic separations on diethylaminoethyl-Sephadex, gel chromatography, and two different electrophoretic procedures. The highly purified was homogeneous when subjected to polyacrylamide gel electrophoresis, ultracentrifugation analyses, and immunochemical determinations. The weight average molecular weight as determined by sedimentation equilibrium ultracentrifugations was 54,000 and by sedimentation diffusion data 55,000. Amino acid analyses indicated a minimum of 110 amino acid residues per molecule. By determination of the minimum in the curve for the fraction of maximum deviation from the amino acid analyses it was found that the minimum molecular weight for the polypeptide was 12,200. Carbohydrate analyses demonstrated the presence f equimolar amounts of amnnose, galactose, and glucosamine, and the carbohydrate portion constituted 7.5% of the total weight. The amino acid analyses suggested that thyroxine-binding globulin is composed of 4 subunits. Molecular weight determinations by gel chromatography in 6 M guanidine hydrochloride indicated the presence of three species of globulin with apparent molecular weights 52,000, 25,000, and 13,500, respectively. Prolonged storage in guanidine hydrochloride promoted a more than 60% yield of the monomeric species. Moreover, a half-molecule of thyroxine-binding globulin was isolated and shown to consist of two polypeptide chains of similar molecular weight..."}
{"id": "PMID:389", "title": "Structural studies of two ovalbumin glycopeptides in relation to the endo-beta-N-acetylglucosaminidase specificity.", "content": "Heterogeneities of the two ovalbumin glycopeptides, (Man)5(GlcNAc)2Asn and (Man)6(GlcNAc)2Asn, were revealed by borate paper electrophoresis of oligosaccharide alcohols obtained from the glycopeptides by endo-beta-N-acetylglucosaminidase H digestion and NaB3H4 reduction. The structures of the major components of the oligosaccharides were determined by the combination of methylation analysis, acetolysis, and alpha-mannosidase digestion. Based on the results, the whole structures of the major components of (Man)5(GlcNAc)2Asn and (Man)6(GlcNAc)2Asn were elucidated as Manalpha1 leads to 6[Manalpha1 leads to 3]-Manalpha1 leads to 6[Manalpha1 leads to 3[Manbeta1 leads to 4GlcNAcbeta1 leads to 4GlcNAc leads to Asn and Manalpha1 leads to 6[Manalpha1 leads to 3]Manalpha1 leads to 6[Manalpha1 leads to 2Manalpha1 leads to 3]Manbeta1 leads to 4GlcNAcbeta1 leads to GlcNAc leads to Asn, respectively. Since endo-beta-N-acetylglucosamini dase D hydrolyzes (Man)5(GlcNAc)2Asn but not (Man)6(GlcNAc)2Asn, the presence of the unsubstituted alpha-mannosyl residue linked at the C-3 position of the terminal mannose of Manbeta1 leads to 4GlcNAcbeta1 leads to 4 GlcNAcAsn core must be essential for the action of the enzyme.", "contents": "Structural studies of two ovalbumin glycopeptides in relation to the endo-beta-N-acetylglucosaminidase specificity. Heterogeneities of the two ovalbumin glycopeptides, (Man)5(GlcNAc)2Asn and (Man)6(GlcNAc)2Asn, were revealed by borate paper electrophoresis of oligosaccharide alcohols obtained from the glycopeptides by endo-beta-N-acetylglucosaminidase H digestion and NaB3H4 reduction. The structures of the major components of the oligosaccharides were determined by the combination of methylation analysis, acetolysis, and alpha-mannosidase digestion. Based on the results, the whole structures of the major components of (Man)5(GlcNAc)2Asn and (Man)6(GlcNAc)2Asn were elucidated as Manalpha1 leads to 6[Manalpha1 leads to 3]-Manalpha1 leads to 6[Manalpha1 leads to 3[Manbeta1 leads to 4GlcNAcbeta1 leads to 4GlcNAc leads to Asn and Manalpha1 leads to 6[Manalpha1 leads to 3]Manalpha1 leads to 6[Manalpha1 leads to 2Manalpha1 leads to 3]Manbeta1 leads to 4GlcNAcbeta1 leads to GlcNAc leads to Asn, respectively. Since endo-beta-N-acetylglucosamini dase D hydrolyzes (Man)5(GlcNAc)2Asn but not (Man)6(GlcNAc)2Asn, the presence of the unsubstituted alpha-mannosyl residue linked at the C-3 position of the terminal mannose of Manbeta1 leads to 4GlcNAcbeta1 leads to 4 GlcNAcAsn core must be essential for the action of the enzyme."}
{"id": "PMID:390", "title": "Use of 5-deazaFAD to study hydrogen transfer in the D-amino acid oxidase reaction.", "content": "The apoprotein of hog kidney D-amino acid oxidase was reconstituted with 5-deazaflavin adenine dinucleotide (5-deazaFAD) to yield a protein which contains 1.5 mol of 5-deazaFAD/mol of enzyme. The deazaFAD-containing enzyme forms complexes with benzoate, 2-amino benzoate, and 4-aminobenzoate which are both qualitatively and quantitatively similar to those observed with native enzyme. The complex with 2-aminobenzoate exhibits a new long wavelength absorption band characteristic of a flavin charge-transfer complex. The reconstituted enzyme exhibits no activity when assayed by D-alanine oxidation. However, the bound chromophore can be reduced by alanine, phenylalanine, proline, methionine, and valine, but not by glutamate or aspartate, indicating the deazaFAD enzyme retains the substrate specificity of the native enzyme. Reduction of the enzyme by D-alanine exhibits a 1.6-fold deuterium isotope effect. Reoxidation of the reduced enzyme occurred in the presence of pyruvate plus ammonia, but not with pyruvate alone or ammonia alone. beta-Phenylpyruvate and alpha-ketobutyrate, but not alpha-ketoglutarate could replace pyruvate. Reduced enzyme isolated following reaction with [alpha-3H]alanine was found to contain 0.5 mol of tritium/mol of deazaFADH2. After denaturation of the tritium-labeled enzyme, the radioactivity was identified as deazaFADH2. Reaction of the reduced tritium-labeled enzyme with pyruvate plus ammonia prior to denaturation yields [alpha-3H]alanine and unlabeled deazaFAD. These results suggest that reduction and reoxidation of enzyme-bound deazaFAD involves the stereo-specific transfer of alpha-hydrogen from substrate to deazaFAD.", "contents": "Use of 5-deazaFAD to study hydrogen transfer in the D-amino acid oxidase reaction. The apoprotein of hog kidney D-amino acid oxidase was reconstituted with 5-deazaflavin adenine dinucleotide (5-deazaFAD) to yield a protein which contains 1.5 mol of 5-deazaFAD/mol of enzyme. The deazaFAD-containing enzyme forms complexes with benzoate, 2-amino benzoate, and 4-aminobenzoate which are both qualitatively and quantitatively similar to those observed with native enzyme. The complex with 2-aminobenzoate exhibits a new long wavelength absorption band characteristic of a flavin charge-transfer complex. The reconstituted enzyme exhibits no activity when assayed by D-alanine oxidation. However, the bound chromophore can be reduced by alanine, phenylalanine, proline, methionine, and valine, but not by glutamate or aspartate, indicating the deazaFAD enzyme retains the substrate specificity of the native enzyme. Reduction of the enzyme by D-alanine exhibits a 1.6-fold deuterium isotope effect. Reoxidation of the reduced enzyme occurred in the presence of pyruvate plus ammonia, but not with pyruvate alone or ammonia alone. beta-Phenylpyruvate and alpha-ketobutyrate, but not alpha-ketoglutarate could replace pyruvate. Reduced enzyme isolated following reaction with [alpha-3H]alanine was found to contain 0.5 mol of tritium/mol of deazaFADH2. After denaturation of the tritium-labeled enzyme, the radioactivity was identified as deazaFADH2. Reaction of the reduced tritium-labeled enzyme with pyruvate plus ammonia prior to denaturation yields [alpha-3H]alanine and unlabeled deazaFAD. These results suggest that reduction and reoxidation of enzyme-bound deazaFAD involves the stereo-specific transfer of alpha-hydrogen from substrate to deazaFAD."}
{"id": "PMID:391", "title": "The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor.", "content": "NSILA-s (nonsuppressible insulin-like activity, soluble in acid ethanol) is a serum peptide that has insulin-like and growth-promoting activities. We have demonstrated previously that liver plasma membranes possess separate receptors for NSILA-s and insulin and have characterized the insulin receptor in detail. In the present study we have characterized the properties and specificity of the NSILA-s receptor and compared them to those of the insulin receptor in the same tissue. Both 125I-NSILA-s and 125I-insulin bind rapidly and reversibly to their receptors in liver membranes; maximal NSILA-s binding occurs at 20 degrees while maximal insulin binding is seen at 1-4 degrees. The pH optimum for NSILA-s binding is broad (6.0 to 8.0), in contrast to the very sharp pH optimum (7.5 to 8.0) for insulin binding. Both receptors exhibit a high degree of specificity. With the insulin receptor, NSILA-s and insulin analogues compete for binding in proportion to their insulin-like potency: insulin greater than proinsulin greater than NSILA-s. With the NSILA-s receptor, NSILA-s is most potent and the order is reversed: NSILA-s greater than proinsulin greater than insulin. Furthermore, six preparations of NSILA-s which varied 70-fold in biological activity competed for 125I-NSILA-s binding in order of their potencies. NSILA-s which had been inactivated biologically by reduction and aminoethylation and growth hormone were less than 1/100,000 as potent as the most purified NSILA-s preparation. Purified preparations of fibroblast growth factor, epidermal growth factor, nerve growth factor, and somatomedins B and C were less than 1% as effective as NSILA-s in competing for the 125I-NSILA-s suggesting that these factors act through other receptors. In contrast, somatomedin A was 10% as active as NSILA-s and multiplication-stimulating activity was fully as active as NSILA-s in competing for the NSILA-s receptor. Analysis of the data suggests that there are approximately 50 times more insulin receptors than NSILA-s receptors per liver cell, while the apparent affinity of NSILA-s receptors is somewhat higher than that of the insulin receptor.", "contents": "The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor. NSILA-s (nonsuppressible insulin-like activity, soluble in acid ethanol) is a serum peptide that has insulin-like and growth-promoting activities. We have demonstrated previously that liver plasma membranes possess separate receptors for NSILA-s and insulin and have characterized the insulin receptor in detail. In the present study we have characterized the properties and specificity of the NSILA-s receptor and compared them to those of the insulin receptor in the same tissue. Both 125I-NSILA-s and 125I-insulin bind rapidly and reversibly to their receptors in liver membranes; maximal NSILA-s binding occurs at 20 degrees while maximal insulin binding is seen at 1-4 degrees. The pH optimum for NSILA-s binding is broad (6.0 to 8.0), in contrast to the very sharp pH optimum (7.5 to 8.0) for insulin binding. Both receptors exhibit a high degree of specificity. With the insulin receptor, NSILA-s and insulin analogues compete for binding in proportion to their insulin-like potency: insulin greater than proinsulin greater than NSILA-s. With the NSILA-s receptor, NSILA-s is most potent and the order is reversed: NSILA-s greater than proinsulin greater than insulin. Furthermore, six preparations of NSILA-s which varied 70-fold in biological activity competed for 125I-NSILA-s binding in order of their potencies. NSILA-s which had been inactivated biologically by reduction and aminoethylation and growth hormone were less than 1/100,000 as potent as the most purified NSILA-s preparation. Purified preparations of fibroblast growth factor, epidermal growth factor, nerve growth factor, and somatomedins B and C were less than 1% as effective as NSILA-s in competing for the 125I-NSILA-s suggesting that these factors act through other receptors. In contrast, somatomedin A was 10% as active as NSILA-s and multiplication-stimulating activity was fully as active as NSILA-s in competing for the NSILA-s receptor. Analysis of the data suggests that there are approximately 50 times more insulin receptors than NSILA-s receptors per liver cell, while the apparent affinity of NSILA-s receptors is somewhat higher than that of the insulin receptor."}
{"id": "PMID:392", "title": "Decarboxylation of oxalacetate to pyruvate by purified avian liver phosphoenolpyruvate carboxykinase.", "content": "Phosphoenolpyruvate carboxykinase, which has been isolated from chicken liver mitochondria in essentially homogenous form, carries out the irreversible decarboxylation of oxalacetate to pyruvate in the presence of catalytic amounts of GDP or IDP, as well as the reversible decarboxylation of oxalacetate to phosphoenolpyruvate in the presence of substrate amounts of GTP or ITP. The pyruvate- and phosphoenolpyruvate-forming reactions are similar in their nucleoside specificity and appear to be carried out by the same protein. However, the two activities vary markedly in their response to added metal ions and sulfhydryl reagents. Phosphoenolpyruvate formation is completely dependent on the presence of a divalent metal ion, with Mn2+ the most effective species. This reaction is also stimulated by sulfhydryl reagents such as 2-mercaptoethanol. In contrast, the pyruvate-forming reaction is strongly inhibited by divalent metal ions, including Mn2+, and also by moderate concentrations of sulfhydryl reagents. These observations and the demonstration that pyruvate kinase-like activity is very low or absent make it unlikely that pyruvate formation proceeds via phosphoenolpyruvate as an intermediate. Although the pyruvate-forming reaction is inhibited by added metal ions, the reaction is also inhibited by metal-chelating agents such as 8-hydroxyquinoline and o-phenanthroline, suggesting that the reaction is dependent on the presence of a metal ion. It has not been possible, however, to demonstrate that the enzyme is a metalloprotein.", "contents": "Decarboxylation of oxalacetate to pyruvate by purified avian liver phosphoenolpyruvate carboxykinase. Phosphoenolpyruvate carboxykinase, which has been isolated from chicken liver mitochondria in essentially homogenous form, carries out the irreversible decarboxylation of oxalacetate to pyruvate in the presence of catalytic amounts of GDP or IDP, as well as the reversible decarboxylation of oxalacetate to phosphoenolpyruvate in the presence of substrate amounts of GTP or ITP. The pyruvate- and phosphoenolpyruvate-forming reactions are similar in their nucleoside specificity and appear to be carried out by the same protein. However, the two activities vary markedly in their response to added metal ions and sulfhydryl reagents. Phosphoenolpyruvate formation is completely dependent on the presence of a divalent metal ion, with Mn2+ the most effective species. This reaction is also stimulated by sulfhydryl reagents such as 2-mercaptoethanol. In contrast, the pyruvate-forming reaction is strongly inhibited by divalent metal ions, including Mn2+, and also by moderate concentrations of sulfhydryl reagents. These observations and the demonstration that pyruvate kinase-like activity is very low or absent make it unlikely that pyruvate formation proceeds via phosphoenolpyruvate as an intermediate. Although the pyruvate-forming reaction is inhibited by added metal ions, the reaction is also inhibited by metal-chelating agents such as 8-hydroxyquinoline and o-phenanthroline, suggesting that the reaction is dependent on the presence of a metal ion. It has not been possible, however, to demonstrate that the enzyme is a metalloprotein."}
{"id": "PMID:394", "title": "Patterns of fatty acid release from endogenous substrates by human platelet homogenates and membranes.", "content": "We describe a method for measuring the release of fatty acids from endogenous substrates of human platelet homogenates and membranes. The method depends on the availability of lipids whose fatty acids are odd-chained and therefore suitable as internal reference compounds that, at the time of lipid extraction, can be added to an incubation to permit subsequent quantification of the content of free fatty acids or fatty acids esterified to specific lipids. We found four types of lipolytic activities in human platelets. In homogenates at pH 4.0 a triglyceride lipase operated as shown by the synchrony of triglyceride degradation and release of glycerol and those fatty acids that are the predominant constituents of triglycerides. However, enough arachidonic acid was released at this pH level to suggest some phospholipid breakdown, since triglycerides hold relatively small amounts of this acid. With membranous preparations, in the alkaline pH range there were two peaks of fatty acid release with accompanying degradation of phospholipids. At pH 8.5, where release of the saturated acids, palmitic and stearic, predominated, their sum was 3.5 times that of arachidonic acid. At pH 9.5 the release of palmitic and stearic acids was only slightly below their peak values; however, the release of arachidonic acid nearly equaled the sum of the saturated acids. Linoleic acid was not released in representative amounts by those reactions that released arachidonic acid, despite the overwhelming propensity of both to be esterified at the 2-position of phospholipids. Pertinently, the choline phospholipids are linoleic-rich and the non-choline phospholipids linoleic-poor, while both have a generous endowment of arachidonic acid. With this in mind, we raise the possibility that the phospholipase A2 of human platelets is an endoenzyme because of its tendency to act on those phospholipids that are thought to comprise the inner layer of the cell membrane.", "contents": "Patterns of fatty acid release from endogenous substrates by human platelet homogenates and membranes. We describe a method for measuring the release of fatty acids from endogenous substrates of human platelet homogenates and membranes. The method depends on the availability of lipids whose fatty acids are odd-chained and therefore suitable as internal reference compounds that, at the time of lipid extraction, can be added to an incubation to permit subsequent quantification of the content of free fatty acids or fatty acids esterified to specific lipids. We found four types of lipolytic activities in human platelets. In homogenates at pH 4.0 a triglyceride lipase operated as shown by the synchrony of triglyceride degradation and release of glycerol and those fatty acids that are the predominant constituents of triglycerides. However, enough arachidonic acid was released at this pH level to suggest some phospholipid breakdown, since triglycerides hold relatively small amounts of this acid. With membranous preparations, in the alkaline pH range there were two peaks of fatty acid release with accompanying degradation of phospholipids. At pH 8.5, where release of the saturated acids, palmitic and stearic, predominated, their sum was 3.5 times that of arachidonic acid. At pH 9.5 the release of palmitic and stearic acids was only slightly below their peak values; however, the release of arachidonic acid nearly equaled the sum of the saturated acids. Linoleic acid was not released in representative amounts by those reactions that released arachidonic acid, despite the overwhelming propensity of both to be esterified at the 2-position of phospholipids. Pertinently, the choline phospholipids are linoleic-rich and the non-choline phospholipids linoleic-poor, while both have a generous endowment of arachidonic acid. With this in mind, we raise the possibility that the phospholipase A2 of human platelets is an endoenzyme because of its tendency to act on those phospholipids that are thought to comprise the inner layer of the cell membrane."}
{"id": "PMID:393", "title": "Hemoglobin Deer Lodge (beta 2 His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site.", "content": "Hemoglobin Deer Lodge is an abnormal human hemoglobin with arginine substituted for histidine at the beta 2 position. X-ray crystallography of normal human hemoglobin has shown that the beta 2 residue is normally part of the binding site for 2,3-diphosphoglycerate. The substitution of arginine for histidine at beta 2 affects both the kinetics and equilibria of ligand binding. When stripped of anions, Hb Deer Lodge has an increased oxygen affinity and a decreased degree of cooperativity relative to Hb A. The alkaline Bohr effect is slightly increased and there are marked increases in oxygen affinity below pH 6 and above pH 8. In the presence of 2,3-diphosphoglycerate the cooperativity in increases to nromal and the pH dependence of oxygen binding is reduced. This contrasts with the enhanced Bohr effect seen for Hb A in the presence of organic phosphates. Due to enhanced anion binding at high pH, Hb Deer Lodge has a slightly lower oxygen affinity than Hb A at pH 9 in the presence of 2,3-diphosphoglycerate or inositol hexaphosphate. Kinetic studies at neutral pH in the absence of organic phosphates revealed biphasicity in the rate of oxygen dissociation from Hb Deer Lodge, while approximately linear time courses were observed for Hb A. The fast phase of the oxygen dissociation kinetics shows great pH sensitivity, and organic phosphates increase the rate and percentage of the fast phase without greatly affecting the slow phase. The two phases are not resolvable at high pH. CO combination kinetics are much like those of Hb A except that \"fast\" and \"slow\" phases were apparent at wavelengths near the deoxy-CO isobestic point. We suggest that functional differences between the alpha and beta chains are enhanced in Hb Deer Lodge. After flash photolysis of the CO derivative, the percentage of quickly reacting material was slightly greater for Hb Deer Lodge than for Hb A. This may imply a somewhat greater tendency to dissociate into high affinity subunits. The substitution of arginine for histidine at beta 2 thus results in a macromolecule whose ligand-binding properties are significantly altered, the primary differences being expressed at high pH where Hb Deer Lodge binds anions more strongly than Hb A. The properties of Hb Deer Lodge are compared to those of other hemoglobin variants with substitutions at residues involved in binding of 2,3-diphosphoglycerate.", "contents": "Hemoglobin Deer Lodge (beta 2 His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site. Hemoglobin Deer Lodge is an abnormal human hemoglobin with arginine substituted for histidine at the beta 2 position. X-ray crystallography of normal human hemoglobin has shown that the beta 2 residue is normally part of the binding site for 2,3-diphosphoglycerate. The substitution of arginine for histidine at beta 2 affects both the kinetics and equilibria of ligand binding. When stripped of anions, Hb Deer Lodge has an increased oxygen affinity and a decreased degree of cooperativity relative to Hb A. The alkaline Bohr effect is slightly increased and there are marked increases in oxygen affinity below pH 6 and above pH 8. In the presence of 2,3-diphosphoglycerate the cooperativity in increases to nromal and the pH dependence of oxygen binding is reduced. This contrasts with the enhanced Bohr effect seen for Hb A in the presence of organic phosphates. Due to enhanced anion binding at high pH, Hb Deer Lodge has a slightly lower oxygen affinity than Hb A at pH 9 in the presence of 2,3-diphosphoglycerate or inositol hexaphosphate. Kinetic studies at neutral pH in the absence of organic phosphates revealed biphasicity in the rate of oxygen dissociation from Hb Deer Lodge, while approximately linear time courses were observed for Hb A. The fast phase of the oxygen dissociation kinetics shows great pH sensitivity, and organic phosphates increase the rate and percentage of the fast phase without greatly affecting the slow phase. The two phases are not resolvable at high pH. CO combination kinetics are much like those of Hb A except that \"fast\" and \"slow\" phases were apparent at wavelengths near the deoxy-CO isobestic point. We suggest that functional differences between the alpha and beta chains are enhanced in Hb Deer Lodge. After flash photolysis of the CO derivative, the percentage of quickly reacting material was slightly greater for Hb Deer Lodge than for Hb A. This may imply a somewhat greater tendency to dissociate into high affinity subunits. The substitution of arginine for histidine at beta 2 thus results in a macromolecule whose ligand-binding properties are significantly altered, the primary differences being expressed at high pH where Hb Deer Lodge binds anions more strongly than Hb A. The properties of Hb Deer Lodge are compared to those of other hemoglobin variants with substitutions at residues involved in binding of 2,3-diphosphoglycerate."}
{"id": "PMID:395", "title": "Oxidation of NADPH by submitochondrial particles from beef heart in complete absence of transhydrogenase activity from NADPH to NAD.", "content": "Treatment of submitochondrial particles (ETP) with trypsin at 0 degrees destroyed NADPH leads to NAD (or 3-acetylpyridine adenine dinucleotide, AcPyAD) transhydrogenase activity. NADH oxidase activity was unaffected; NADPH oxidase and NADH leads to AcPyAD transhydrogenase activities were diminished by less than 10%. When ETP was incubated with trypsin at 30 degrees, NADPH leads to NAD transhydrogenase activity was rapidly lost, NADPH oxidase activity was slowly destroyed, but NADH oxidase activity remained intact. The reduction pattern by NADPH, NADPH + NAD, and NADH of chromophores absorbing at 475 minus 510 nm (flavin and iron-sulfur centers) in complex I (NADH-ubiquinone reductase) or ETP treated with trypsin at 0 degrees also indicated specific destruction of transhydrogenase activity. The sensitivity of the NADPH leads to NAD transhydrogenase reaction to trypsin suggested the involvement of susceptible arginyl residues in the enzyme. Arginyl residues are considered to be positively charged binding sites for anionic substrates and ligands in many enzymes. Treatment of ETP with the specific arginine-binding reagent, butanedione, inhibited transhydrogenation from NADPH leads to NAD (or AcPyAD). It had no effect on NADH oxidation, and inhibited NADPH oxidation and NADH leads to AcPyAD transhydrogenation by only 10 to 15% even after 30 to 60 min incubation of ETP with butanedione. The inhibition of NADPH leads to NAD transhydrogenation was diminished considerably when butanedione was added to ETP in the presence of NAD or NADP. When both NAD and NADP were present, the butanedione effect was completely abolished, thus suggesting the possible presence of arginyl residues at the nucleotide binding site of the NADPH leads to NAD transhydrogenase enzyme. Under conditions that transhydrogenation from NADPH to NAD was completely inhibited by trypsin or butanedione, NADPH oxidation rate was larger than or equal to 220 nmol min-1 mg-1 ETP protein at pH 6.0 and 30 degrees. The above results establish that in the respiratory chain of beef-heart mitochondria NADH oxidation, NADPH oxidation, and NADPH leads to NAD transhydrogenation are independent reactions.", "contents": "Oxidation of NADPH by submitochondrial particles from beef heart in complete absence of transhydrogenase activity from NADPH to NAD. Treatment of submitochondrial particles (ETP) with trypsin at 0 degrees destroyed NADPH leads to NAD (or 3-acetylpyridine adenine dinucleotide, AcPyAD) transhydrogenase activity. NADH oxidase activity was unaffected; NADPH oxidase and NADH leads to AcPyAD transhydrogenase activities were diminished by less than 10%. When ETP was incubated with trypsin at 30 degrees, NADPH leads to NAD transhydrogenase activity was rapidly lost, NADPH oxidase activity was slowly destroyed, but NADH oxidase activity remained intact. The reduction pattern by NADPH, NADPH + NAD, and NADH of chromophores absorbing at 475 minus 510 nm (flavin and iron-sulfur centers) in complex I (NADH-ubiquinone reductase) or ETP treated with trypsin at 0 degrees also indicated specific destruction of transhydrogenase activity. The sensitivity of the NADPH leads to NAD transhydrogenase reaction to trypsin suggested the involvement of susceptible arginyl residues in the enzyme. Arginyl residues are considered to be positively charged binding sites for anionic substrates and ligands in many enzymes. Treatment of ETP with the specific arginine-binding reagent, butanedione, inhibited transhydrogenation from NADPH leads to NAD (or AcPyAD). It had no effect on NADH oxidation, and inhibited NADPH oxidation and NADH leads to AcPyAD transhydrogenation by only 10 to 15% even after 30 to 60 min incubation of ETP with butanedione. The inhibition of NADPH leads to NAD transhydrogenation was diminished considerably when butanedione was added to ETP in the presence of NAD or NADP. When both NAD and NADP were present, the butanedione effect was completely abolished, thus suggesting the possible presence of arginyl residues at the nucleotide binding site of the NADPH leads to NAD transhydrogenase enzyme. Under conditions that transhydrogenation from NADPH to NAD was completely inhibited by trypsin or butanedione, NADPH oxidation rate was larger than or equal to 220 nmol min-1 mg-1 ETP protein at pH 6.0 and 30 degrees. The above results establish that in the respiratory chain of beef-heart mitochondria NADH oxidation, NADPH oxidation, and NADPH leads to NAD transhydrogenation are independent reactions."}
{"id": "PMID:396", "title": "Protein inhibitor of acid deoxyribonucleases. Improved purification procedure and properties.", "content": "A method is described for the extensive purification of acid deoxyribonuclease (acid DNase) and its specific inhibitor from beef liver, the existence of which had been only supported by indirect evidence. By the use of insolubilized acid deoxyribonuclease, eight other proteins interacting with the enzyme have been detected. One of them (molecular weight, 59,000) was identified as responsible for phosphodiesterase activity which is often a contaminant of DNase preparations. Acid DNase (free of phosphodiesterase) and its inhibitor have been obtained as homogeneous proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of acid DNase and its inhibitor are, respectively, 26,500 and 21,500; those of other proteins range from 17,000 to 112,000. The properties of beef liver acid DNase are similar to those described for the enzymes extracted from other sources. The same alteration of DNase kinetics by this inhibitor, as that previously demonstrated with an impure protein has been confirmed; the sigmoidal shape observed at pH 5 for the plot of initial rate versus substrate concentration progressively disappears with increasing pH. We have also demonstrated that RNA, which inhibits the acid DNase through a competitive binding to the catalytic site, is able, like the substrate, to reverse the binding of inhibitor to the enzyme.", "contents": "Protein inhibitor of acid deoxyribonucleases. Improved purification procedure and properties. A method is described for the extensive purification of acid deoxyribonuclease (acid DNase) and its specific inhibitor from beef liver, the existence of which had been only supported by indirect evidence. By the use of insolubilized acid deoxyribonuclease, eight other proteins interacting with the enzyme have been detected. One of them (molecular weight, 59,000) was identified as responsible for phosphodiesterase activity which is often a contaminant of DNase preparations. Acid DNase (free of phosphodiesterase) and its inhibitor have been obtained as homogeneous proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of acid DNase and its inhibitor are, respectively, 26,500 and 21,500; those of other proteins range from 17,000 to 112,000. The properties of beef liver acid DNase are similar to those described for the enzymes extracted from other sources. The same alteration of DNase kinetics by this inhibitor, as that previously demonstrated with an impure protein has been confirmed; the sigmoidal shape observed at pH 5 for the plot of initial rate versus substrate concentration progressively disappears with increasing pH. We have also demonstrated that RNA, which inhibits the acid DNase through a competitive binding to the catalytic site, is able, like the substrate, to reverse the binding of inhibitor to the enzyme."}
{"id": "PMID:397", "title": "Nucleotide-metabolizing enzymes in Chlamydomonas flagella.", "content": "Nucleotides have at least two functions in eukaryotic cilia and flagella. ATP, originating in the cells, is utilized for motility by energy-transducing protein(s) called dynein, and the binding of guanine nucleotides to tubulin, and probably certain transformations of the bound nucleotides, are prerequisites for the assembly of microtubules. Besides dynein, which can be solubulized from Chlamydomonas flagella as a heterogeneous, Mg2+ or Ca2+-activated ATPase, we have purified and characterized five other flagellar enzymes involved in nucleotide transformations. A homogeneous, low molecular weight, Ca2+-specific adenosine triphosphatase was isolated, which was inhibited by Mg2+ and was not specific for ATP. This enzyme was not formed by treating purified dynein with proteases. It was absent from extracts of Tetrahymena cilia. Its function might be an auxiliary energy transducer, or in steering or tactic responses. Two species of adenylate kinase were isolated, one of which was much elevated in regenerating flagella; the latter was also present in cell bodies. A large part of flagellar nucleoside diphosphokinase activity could not be solubilized. Two soluble enzyme species were identified, one of which was also present in cell bodies. Since these enzymes are of interest because they might function in microtubule assembly, we studied the extent to which brain nucleoside diphosphokinase co-polymerizes with tubulin purified by repeated cycles of polymerization. Arginine kinase was not detected in Chlamydomonas flagellar extracts.", "contents": "Nucleotide-metabolizing enzymes in Chlamydomonas flagella. Nucleotides have at least two functions in eukaryotic cilia and flagella. ATP, originating in the cells, is utilized for motility by energy-transducing protein(s) called dynein, and the binding of guanine nucleotides to tubulin, and probably certain transformations of the bound nucleotides, are prerequisites for the assembly of microtubules. Besides dynein, which can be solubulized from Chlamydomonas flagella as a heterogeneous, Mg2+ or Ca2+-activated ATPase, we have purified and characterized five other flagellar enzymes involved in nucleotide transformations. A homogeneous, low molecular weight, Ca2+-specific adenosine triphosphatase was isolated, which was inhibited by Mg2+ and was not specific for ATP. This enzyme was not formed by treating purified dynein with proteases. It was absent from extracts of Tetrahymena cilia. Its function might be an auxiliary energy transducer, or in steering or tactic responses. Two species of adenylate kinase were isolated, one of which was much elevated in regenerating flagella; the latter was also present in cell bodies. A large part of flagellar nucleoside diphosphokinase activity could not be solubilized. Two soluble enzyme species were identified, one of which was also present in cell bodies. Since these enzymes are of interest because they might function in microtubule assembly, we studied the extent to which brain nucleoside diphosphokinase co-polymerizes with tubulin purified by repeated cycles of polymerization. Arginine kinase was not detected in Chlamydomonas flagellar extracts."}
{"id": "PMID:398", "title": "In vitro biosynthesis of sialosylgalactosylceramide (G7) by mouse brain microsomes.", "content": "A sialytransferase activity which catalyzes the synthesis of sialosylgalactosylceramide (G7) from added galactocerebroside and CMP-N-acetylneuraminic acid has been demonstrated in mouse brain microsomes. The enzyme reaction shows a pH optimum of 6.3 and requires detergents. Both Mn2+ and Ca2+ inhibited the reaction, whereas Mg2+ had no effect. The apparent Km for galactocerebroside leading to G7 was estimated to be 8.7 X 10(-4) M. The same microsomal preparation also synthesized hematoside when ceramide lactoside was the glycolipid acceptor. The apparent Km for ceramide lactoside was about one-tenth that for galactocerebroside. When the preparations were partially inactivated by heat the synthesis of G7 and of hematoside was reduced at approximately the same rate. Liver appeared to have the highest activity for G7 synthesis (as well as of hematoside), followed by brain. The synthesis of B7 by mouse brain microsomes in vitro demonstrates a new pathway for brain ganglioside synthesis.", "contents": "In vitro biosynthesis of sialosylgalactosylceramide (G7) by mouse brain microsomes. A sialytransferase activity which catalyzes the synthesis of sialosylgalactosylceramide (G7) from added galactocerebroside and CMP-N-acetylneuraminic acid has been demonstrated in mouse brain microsomes. The enzyme reaction shows a pH optimum of 6.3 and requires detergents. Both Mn2+ and Ca2+ inhibited the reaction, whereas Mg2+ had no effect. The apparent Km for galactocerebroside leading to G7 was estimated to be 8.7 X 10(-4) M. The same microsomal preparation also synthesized hematoside when ceramide lactoside was the glycolipid acceptor. The apparent Km for ceramide lactoside was about one-tenth that for galactocerebroside. When the preparations were partially inactivated by heat the synthesis of G7 and of hematoside was reduced at approximately the same rate. Liver appeared to have the highest activity for G7 synthesis (as well as of hematoside), followed by brain. The synthesis of B7 by mouse brain microsomes in vitro demonstrates a new pathway for brain ganglioside synthesis."}
{"id": "PMID:399", "title": "Proteolytic enzymes of the K-1 strain of Streptomyces griseus obtained from a commercial preparation (Pronase). Purification and characterization of the carboxypeptidase.", "content": "We described earlier the facilitated purifications of the trypsin and aminopeptidase components present in Pronase (Vosbeck, K. D., Chow, K. -F., and Awad, W. M., Jr. (1973) J. Biol. Chem. 248, 6029-6034). A partially resolved protein mixture left over after one of the steps in that procedure was passed through a Sephadex G-75 column. By this means, a component with carboxypeptidase activity was separated from associated serine endopeptidases. Further purification of this exopeptidase to apparent homogeneity was acheived by refiltration through the same Sephadex column and by CM-cellulose chromatography. A single protein band was observed after acrylamide gel electrophoresis; analysis by sedimentation equilibrium using the meniscus depletion method gave a molecular weight of 30,300. This enzyme demonstrates activity against Nalpha-benzyloxycarbonylglycyl-L-leucine and hippuryl-D,L-phenyllactate; no activity was found against Nalpha-acetyl-L-tyrosine ethyl ester, Nalpha-benzoyl-D,L-arginine-p-nitroanilide, or L-leuckne-p-nitroanilide. The maximum activity lies between pH values of 7 and 8; the enzyme is stable between pH values of 6 and 10. At room temperature 1,10-phenanthroline inactivates the enzyme completely whereas EDTA has no effect. Of the many cations tested, only Co2+, Ni2+, or Zn2+ restores activity to the 1,10-phenanthroline-treated enzyme; Co2+ provided 3 times the native activity. The metal in the native protein was found to be zinc. These findings are similar to those recorded with bovine pancreatic carboxypeptidase A, and suggest the possibility that the present enzyme may ge genetically related to the mammalian protein, as in previously noted examples of homology of three Pronase endopeptidases to pancreatic serine enzymes.", "contents": "Proteolytic enzymes of the K-1 strain of Streptomyces griseus obtained from a commercial preparation (Pronase). Purification and characterization of the carboxypeptidase. We described earlier the facilitated purifications of the trypsin and aminopeptidase components present in Pronase (Vosbeck, K. D., Chow, K. -F., and Awad, W. M., Jr. (1973) J. Biol. Chem. 248, 6029-6034). A partially resolved protein mixture left over after one of the steps in that procedure was passed through a Sephadex G-75 column. By this means, a component with carboxypeptidase activity was separated from associated serine endopeptidases. Further purification of this exopeptidase to apparent homogeneity was acheived by refiltration through the same Sephadex column and by CM-cellulose chromatography. A single protein band was observed after acrylamide gel electrophoresis; analysis by sedimentation equilibrium using the meniscus depletion method gave a molecular weight of 30,300. This enzyme demonstrates activity against Nalpha-benzyloxycarbonylglycyl-L-leucine and hippuryl-D,L-phenyllactate; no activity was found against Nalpha-acetyl-L-tyrosine ethyl ester, Nalpha-benzoyl-D,L-arginine-p-nitroanilide, or L-leuckne-p-nitroanilide. The maximum activity lies between pH values of 7 and 8; the enzyme is stable between pH values of 6 and 10. At room temperature 1,10-phenanthroline inactivates the enzyme completely whereas EDTA has no effect. Of the many cations tested, only Co2+, Ni2+, or Zn2+ restores activity to the 1,10-phenanthroline-treated enzyme; Co2+ provided 3 times the native activity. The metal in the native protein was found to be zinc. These findings are similar to those recorded with bovine pancreatic carboxypeptidase A, and suggest the possibility that the present enzyme may ge genetically related to the mammalian protein, as in previously noted examples of homology of three Pronase endopeptidases to pancreatic serine enzymes."}
{"id": "PMID:400", "title": "Trypsin-sensitive photosynthetic activities in chloroplast membranes from Chlamydomonas reinhardi, y-1.", "content": "Location of electron transport chain components in chloroplast membranes of chlamydomonas reinhardi, y-1 was investigated by use of proteolytic digestion with soluble or insolubilized trypsin. Digestion of intact membrane vesicles with soluble trypsin inactivates the water-splitting system, the 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition site of Photosystem II, the electron transport between the two photosystems as well as the ferredoxin NADP reductase. Reduction of NADP with artificial electron donors for Photosystem I could be restored, however, by addition of purified reductase to trypsin-digested membranes. Electron transfer activities of Photosystems I and II reaction centers were resistant to trypsin digestion either from outside or from within the thylakoids when active trypsin was trapped inside the membrane vesicles by sonication and digestion carried out in the presence of trypsin inhibitor added from outside. In the latter case, the water-splitting system was also found to be resistant to digestion. Polyacrylamide-bound insolubilized trypsin inactivated only the ferredoxin NADP reductase. Photosynthetically active membranes obtained at different stages of development showed a basically similar behavior toward trypsin.", "contents": "Trypsin-sensitive photosynthetic activities in chloroplast membranes from Chlamydomonas reinhardi, y-1. Location of electron transport chain components in chloroplast membranes of chlamydomonas reinhardi, y-1 was investigated by use of proteolytic digestion with soluble or insolubilized trypsin. Digestion of intact membrane vesicles with soluble trypsin inactivates the water-splitting system, the 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition site of Photosystem II, the electron transport between the two photosystems as well as the ferredoxin NADP reductase. Reduction of NADP with artificial electron donors for Photosystem I could be restored, however, by addition of purified reductase to trypsin-digested membranes. Electron transfer activities of Photosystems I and II reaction centers were resistant to trypsin digestion either from outside or from within the thylakoids when active trypsin was trapped inside the membrane vesicles by sonication and digestion carried out in the presence of trypsin inhibitor added from outside. In the latter case, the water-splitting system was also found to be resistant to digestion. Polyacrylamide-bound insolubilized trypsin inactivated only the ferredoxin NADP reductase. Photosynthetically active membranes obtained at different stages of development showed a basically similar behavior toward trypsin."}
{"id": "PMID:401", "title": "A complex of cardiac cytochrome c1 and cytochrome c.", "content": "The interactions of cytochrome c1 and cytochrome c from bovine cardiac mitochondria were investigated. Cytochrome c1 and cytochrome c formed a 1:1 molecular complex in aqueous solutions of low ionic strength. The complex was stable to Sephadex G-75 chromatography. The formation and stability of the complex were independent of the oxidation state of the cytochrome components as far as those reactions studied were concerned. The complex was dissociated in solutions of ionic strength higher than 0.07 or pH exceeding 10 and only partially dissociated in 8 M urea. No complexation occurred when cytochrome c was acetylated on 64% of its lysine residues or photooxidized on its 2 methionine residues. Complexes with molecular ratios of less than 1:1 (i.e. more cytochrome c) were obtained when polymerized cytochrome c, or cytochrome c with all lysine residues guanidinated, or a \"1-65 heme peptide\" from cyanogen bromide cleavage of cytochrome c was used. These results were interpreted to imply that the complex was predominantly maintained by ionic interactions probably involving some of the lysine residues of cytochrome c but with major stabilization dependent on the native conformations of both cytochromes. The reduced complex was autooxidizable with biphasic kinetics with first order rate constants of 6 X 10(-5) and 5 X U0(-5) s-1 but did not react with carbon monoxide. The complex reacted with cyanide and was reduced by ascorbate at about 32% and 40% respectively, of the rates of reaction with cytochrome c alone. The complex was less photoreducible than cytochrome c1 alone. The complex exhibited remarkably different circular dichroic behavior from that of the summation of cytochrome c1 plus cytochrome c. We concluded that when cytochromes c1 and c interacted they underwent dramatic conformational changes resulting in weakening of their heme crevices. All results available would indicate that in the complex cytochrome c1 was bound at the entrance to the heme crevice of cytochrome c on the methionine-80 side of the heme crevice.", "contents": "A complex of cardiac cytochrome c1 and cytochrome c. The interactions of cytochrome c1 and cytochrome c from bovine cardiac mitochondria were investigated. Cytochrome c1 and cytochrome c formed a 1:1 molecular complex in aqueous solutions of low ionic strength. The complex was stable to Sephadex G-75 chromatography. The formation and stability of the complex were independent of the oxidation state of the cytochrome components as far as those reactions studied were concerned. The complex was dissociated in solutions of ionic strength higher than 0.07 or pH exceeding 10 and only partially dissociated in 8 M urea. No complexation occurred when cytochrome c was acetylated on 64% of its lysine residues or photooxidized on its 2 methionine residues. Complexes with molecular ratios of less than 1:1 (i.e. more cytochrome c) were obtained when polymerized cytochrome c, or cytochrome c with all lysine residues guanidinated, or a \"1-65 heme peptide\" from cyanogen bromide cleavage of cytochrome c was used. These results were interpreted to imply that the complex was predominantly maintained by ionic interactions probably involving some of the lysine residues of cytochrome c but with major stabilization dependent on the native conformations of both cytochromes. The reduced complex was autooxidizable with biphasic kinetics with first order rate constants of 6 X 10(-5) and 5 X U0(-5) s-1 but did not react with carbon monoxide. The complex reacted with cyanide and was reduced by ascorbate at about 32% and 40% respectively, of the rates of reaction with cytochrome c alone. The complex was less photoreducible than cytochrome c1 alone. The complex exhibited remarkably different circular dichroic behavior from that of the summation of cytochrome c1 plus cytochrome c. We concluded that when cytochromes c1 and c interacted they underwent dramatic conformational changes resulting in weakening of their heme crevices. All results available would indicate that in the complex cytochrome c1 was bound at the entrance to the heme crevice of cytochrome c on the methionine-80 side of the heme crevice."}
{"id": "PMID:402", "title": "Leucine aminopeptidase (bovine lens). Effect of pH on the relative binding of Zn2+ and Mg2+ to and on activation of the enzyme.", "content": "Incubation of leucine aminopeptidase (bovine lens) (EC 3.4.1.1) with various concentrations of Mg2+ at various pH values in 1 M KCl and 0.155 M trimethylamine-HCl at 37 degrees confirms that Mg2+ competes with Zn2+ for binding only 1 site per 54,000-dalton subunit. The ratio of the apparent association constants (1KZn:1KMg = 1KZn/Mg) at this site (site 1) was estimated to be 20,720 at pH 8.16, 10,570 at pH 8.44, 3,590 at pH 8.78, and 660 AT PH 9.14. The decrease in values of 1KZn/Mg with increasing pH in the activation of leucine aminopeptidase by Mg2+ is attributed to the lowering of the free Zn2+ concentration relative to that of free Mg2+ caused by the formation of ZnOH+ and Zn(OH)2 complexes with increasing OH- concentration. When corrections are made for the binding of Zn2+ by OH- ions, the pH-independent ratio of association constants (1KZn:1KMg = 1KZn/Mg) for the relative binding of Zn2+ and Mg2+ at site 1 of leucine aminopeptidase in 29,800. From the effect of pH on the relative binding constant, a value (beta2) for the product of the two stepwise association constants for the formation of Zn(OH)2 from Zn2+ and OH- (Zn2+ + OH- in equilibrium ZnOH+; ZnOH+ + OH- in equilibrium Zn(OH)2) was estimated to be 4.42 X 10(10) M-2 at 37 degrees. Values of Km at pH 7.5 AND 30 degrees with L-leucine p-nitroanilide as substrate in the presence of 0.01 M NaHCO3 are 4.13 and 2.01 mM for the zinc-zinc and magnesium-zinc enzymes, respectively. Values for Vmax are 0.2 and 2.49 mumol/min/mg, respectively.", "contents": "Leucine aminopeptidase (bovine lens). Effect of pH on the relative binding of Zn2+ and Mg2+ to and on activation of the enzyme. Incubation of leucine aminopeptidase (bovine lens) (EC 3.4.1.1) with various concentrations of Mg2+ at various pH values in 1 M KCl and 0.155 M trimethylamine-HCl at 37 degrees confirms that Mg2+ competes with Zn2+ for binding only 1 site per 54,000-dalton subunit. The ratio of the apparent association constants (1KZn:1KMg = 1KZn/Mg) at this site (site 1) was estimated to be 20,720 at pH 8.16, 10,570 at pH 8.44, 3,590 at pH 8.78, and 660 AT PH 9.14. The decrease in values of 1KZn/Mg with increasing pH in the activation of leucine aminopeptidase by Mg2+ is attributed to the lowering of the free Zn2+ concentration relative to that of free Mg2+ caused by the formation of ZnOH+ and Zn(OH)2 complexes with increasing OH- concentration. When corrections are made for the binding of Zn2+ by OH- ions, the pH-independent ratio of association constants (1KZn:1KMg = 1KZn/Mg) for the relative binding of Zn2+ and Mg2+ at site 1 of leucine aminopeptidase in 29,800. From the effect of pH on the relative binding constant, a value (beta2) for the product of the two stepwise association constants for the formation of Zn(OH)2 from Zn2+ and OH- (Zn2+ + OH- in equilibrium ZnOH+; ZnOH+ + OH- in equilibrium Zn(OH)2) was estimated to be 4.42 X 10(10) M-2 at 37 degrees. Values of Km at pH 7.5 AND 30 degrees with L-leucine p-nitroanilide as substrate in the presence of 0.01 M NaHCO3 are 4.13 and 2.01 mM for the zinc-zinc and magnesium-zinc enzymes, respectively. Values for Vmax are 0.2 and 2.49 mumol/min/mg, respectively."}
{"id": "PMID:403", "title": "Biochemical studies of tast sensation. Binding of L-[3H]alanine to a sedimentable fraction from catfish barbel epithelium.", "content": "Large numbers of taste buds are distributed over the body surface of the channel catfish ictalurus punctatus, with the barbels having an especially high density. L-Alanine, as well as certain other amino acids, are taste stimuli in this animal. Epithelial tissue obtained by gentle scraping of the barbel surface was fractionated by differential centrifugation. A sedimentable fraction (P2) was prepared that was enriched in L[OH]alanine binding activity, the plasma membrane marker enzyme 5'-nucleotidase, and the mitochondrial marker succinate cytochrome c reductase, but not the microsomal marker NADH cytochrome c redu.ctase. Binding of L-[OH]alanine was measured using a Millipore filter method in which correction for non-specific binding was also determined. Time, temperature, and pH for measuring binding activity were established. At the optimal pH of 7.8, the KD for L-alanine is 4.8 X 10(-6) M. The first order dissociation rate constant at 6 degrees is 3.8 X 10(-4) s-1 and at 24 degrees it is 12.1 X 10(-4) s-1. The second order rate constant for association is between 10(2) and 10(3) M-1 S-1. Reversibility of the binding interaction was also demonstrates by the rapid displacement of bound L-[3H]alanine by a large excess of unlabeled L-alanine. That the binding does not represent incorporation into protein was confirmed by the lack of effect of puromycin. The amounts bound of several other chemostimulatory amino acids werealso determined.", "contents": "Biochemical studies of tast sensation. Binding of L-[3H]alanine to a sedimentable fraction from catfish barbel epithelium. Large numbers of taste buds are distributed over the body surface of the channel catfish ictalurus punctatus, with the barbels having an especially high density. L-Alanine, as well as certain other amino acids, are taste stimuli in this animal. Epithelial tissue obtained by gentle scraping of the barbel surface was fractionated by differential centrifugation. A sedimentable fraction (P2) was prepared that was enriched in L[OH]alanine binding activity, the plasma membrane marker enzyme 5'-nucleotidase, and the mitochondrial marker succinate cytochrome c reductase, but not the microsomal marker NADH cytochrome c redu.ctase. Binding of L-[OH]alanine was measured using a Millipore filter method in which correction for non-specific binding was also determined. Time, temperature, and pH for measuring binding activity were established. At the optimal pH of 7.8, the KD for L-alanine is 4.8 X 10(-6) M. The first order dissociation rate constant at 6 degrees is 3.8 X 10(-4) s-1 and at 24 degrees it is 12.1 X 10(-4) s-1. The second order rate constant for association is between 10(2) and 10(3) M-1 S-1. Reversibility of the binding interaction was also demonstrates by the rapid displacement of bound L-[3H]alanine by a large excess of unlabeled L-alanine. That the binding does not represent incorporation into protein was confirmed by the lack of effect of puromycin. The amounts bound of several other chemostimulatory amino acids werealso determined."}
{"id": "PMID:404", "title": "Arterialization of the coronary veins in diffuse coronary arteriosclerosis.", "content": "Since the coronary veins and capillaries are not involved with arteriosclerotic disease the authors performed experimental, and afterwards, clinical total and selective coronary vein arterialization. Acute myocardial ischaemia created for instance by ligation of the anterior descending branch, was treated by an internal mammary artery to regional coronary vein anastomosis. In 21 patients the selective arterialization of the \"Vena cordis magna\" or of \"Vena cordis media\", and total arterialization of the coronary sinus was performed. The clinical improvement and follow-up studies seem to be promising in the treatment of patients with advanced diffuse heavy coronary arteriosclerosis. In acute myocardial ischaemia with coronarographically localized coronary occlusion, the aim of regional vein arterialization is to minimize the area of infarction.", "contents": "Arterialization of the coronary veins in diffuse coronary arteriosclerosis. Since the coronary veins and capillaries are not involved with arteriosclerotic disease the authors performed experimental, and afterwards, clinical total and selective coronary vein arterialization. Acute myocardial ischaemia created for instance by ligation of the anterior descending branch, was treated by an internal mammary artery to regional coronary vein anastomosis. In 21 patients the selective arterialization of the \"Vena cordis magna\" or of \"Vena cordis media\", and total arterialization of the coronary sinus was performed. The clinical improvement and follow-up studies seem to be promising in the treatment of patients with advanced diffuse heavy coronary arteriosclerosis. In acute myocardial ischaemia with coronarographically localized coronary occlusion, the aim of regional vein arterialization is to minimize the area of infarction."}
{"id": "PMID:406", "title": "Structure, composition, physical properties, and turnover of proliferated peroxisomes. A study of the trophic effects of Su-13437 on rat liver.", "content": "Peroxisome proliferation has been induced with 2-methyl-2-(p-[1,2,3,4-tetrahydro-1-naphthyl]-phenoxy)-propionic acid (Su-13437). DNA, protein, cytochrome oxidase, glucose-6-phosphatase, and acid phosphatase concentrations remain almost constant. Peroxisomal enzyme activities change to approximately 165%, 50%, 30%, and 0% of the controls for catalase, urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase, respectively. For catalase the change results from a decrease in particle-bound activity and a fivefold increase in soluble activity. The average diameter of peroxisome sections is 0.58 +/- 0.15 mum in controls and 0.73 +/- 0.25 mum after treatment. Therefore, the measured peroxisomal enzymes are highly diluted in proliferated particles. After tissue fractionation, approximately one-half of the normal peroxisomes and all proliferated peroxisomes show matric extraction with ghost formation, but no change in size. In homogenates submitted to mechanical stress, proliferated peroxisomes do not reveal increased fragility; unexpectedly, Su-13437 stabilizes lysosomes. Our results suggest that matrix extraction and increased soluble enzyme activities result from transmembrane passage of peroxisomal proteins. The changes in concentration of peroxisomal oxidases and soluble catalase after Su-13437 allow the calculation of their half-lives. These are the same as those found for total catalase, in normal and treated rats, after allyl isopropyl acetamide: about 1.3 days, a result compatible with peroxisome degradation by autophagy. A sequential increase in liver RNA concentration, [14C]leucine incorporation into DOC-soluble proteins and into immunoprecipitable catalase, and an increase in liver size and peroxisomal volume per gram liver, characterize the trophic effect of the drug used. In males, Su-13437 is more active than CPIB, another peroxisome proliferation-inducing drug; in females, only Su-13437 is active.", "contents": "Structure, composition, physical properties, and turnover of proliferated peroxisomes. A study of the trophic effects of Su-13437 on rat liver. Peroxisome proliferation has been induced with 2-methyl-2-(p-[1,2,3,4-tetrahydro-1-naphthyl]-phenoxy)-propionic acid (Su-13437). DNA, protein, cytochrome oxidase, glucose-6-phosphatase, and acid phosphatase concentrations remain almost constant. Peroxisomal enzyme activities change to approximately 165%, 50%, 30%, and 0% of the controls for catalase, urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase, respectively. For catalase the change results from a decrease in particle-bound activity and a fivefold increase in soluble activity. The average diameter of peroxisome sections is 0.58 +/- 0.15 mum in controls and 0.73 +/- 0.25 mum after treatment. Therefore, the measured peroxisomal enzymes are highly diluted in proliferated particles. After tissue fractionation, approximately one-half of the normal peroxisomes and all proliferated peroxisomes show matric extraction with ghost formation, but no change in size. In homogenates submitted to mechanical stress, proliferated peroxisomes do not reveal increased fragility; unexpectedly, Su-13437 stabilizes lysosomes. Our results suggest that matrix extraction and increased soluble enzyme activities result from transmembrane passage of peroxisomal proteins. The changes in concentration of peroxisomal oxidases and soluble catalase after Su-13437 allow the calculation of their half-lives. These are the same as those found for total catalase, in normal and treated rats, after allyl isopropyl acetamide: about 1.3 days, a result compatible with peroxisome degradation by autophagy. A sequential increase in liver RNA concentration, [14C]leucine incorporation into DOC-soluble proteins and into immunoprecipitable catalase, and an increase in liver size and peroxisomal volume per gram liver, characterize the trophic effect of the drug used. In males, Su-13437 is more active than CPIB, another peroxisome proliferation-inducing drug; in females, only Su-13437 is active."}
{"id": "PMID:407", "title": "Localization of NADH oxidase on the surface of human polymorphonuclear leukocytes by a new cytochemical method.", "content": "The ultrastructural localization of NADH oxidase, a possible enzyme in the increased oxidative activity of polymorphonuclear leukocytes (PMN) during phagocytosis, was studied. A new cytochemical technique for the localization of H2O2, a product of NADH oxidase activity, was developed. Cerous ions, in the presence of peroxide, form an electron-dense precipitate. Resting and phagocytically stimulated PMN were exposed to cerous ions at pH 7.5 to demonstrate sites of NADH-dependent, cyanide-insensitive H2O2 production. Resting PMN exhibites slight activity on the plasma membrane; phagocytizing PMN had extensive deposits of reaction product localized within the phagosome and on the plasma membrane. Peroxide involvement was demonstrated by the inhibitory effect of catalase on cerium precipitation; the surface localization of the enzyme responsible was confirmed by using nonpenetrating inhibitors of enzymatic activity. A correlative study was performed with an NADH-dependent, tetrazolium-reduction system. As with cerium, formazan deposition on the surface of the cell was NADH dependent, cyanide insensitive, and stimulated by phagocytosis. Superoxide dismutase did not inhibit tetrazolium reduction, as observed cytochemically, indicating direct enzymatic dye reduction without superoxide interposition. These findings, combined with oxygen consumption studies on resting and stimulated PMN in the presence or absence of NADH, indicate that NADH oxidase is a surface enzyme in human PMN. It is internalized during phagocytosis and retains its peroxide-generating capacity within the phagocytic vacuole.", "contents": "Localization of NADH oxidase on the surface of human polymorphonuclear leukocytes by a new cytochemical method. The ultrastructural localization of NADH oxidase, a possible enzyme in the increased oxidative activity of polymorphonuclear leukocytes (PMN) during phagocytosis, was studied. A new cytochemical technique for the localization of H2O2, a product of NADH oxidase activity, was developed. Cerous ions, in the presence of peroxide, form an electron-dense precipitate. Resting and phagocytically stimulated PMN were exposed to cerous ions at pH 7.5 to demonstrate sites of NADH-dependent, cyanide-insensitive H2O2 production. Resting PMN exhibites slight activity on the plasma membrane; phagocytizing PMN had extensive deposits of reaction product localized within the phagosome and on the plasma membrane. Peroxide involvement was demonstrated by the inhibitory effect of catalase on cerium precipitation; the surface localization of the enzyme responsible was confirmed by using nonpenetrating inhibitors of enzymatic activity. A correlative study was performed with an NADH-dependent, tetrazolium-reduction system. As with cerium, formazan deposition on the surface of the cell was NADH dependent, cyanide insensitive, and stimulated by phagocytosis. Superoxide dismutase did not inhibit tetrazolium reduction, as observed cytochemically, indicating direct enzymatic dye reduction without superoxide interposition. These findings, combined with oxygen consumption studies on resting and stimulated PMN in the presence or absence of NADH, indicate that NADH oxidase is a surface enzyme in human PMN. It is internalized during phagocytosis and retains its peroxide-generating capacity within the phagocytic vacuole."}
{"id": "PMID:408", "title": "Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi (beige) mice.", "content": "The beige mouse is an animal model for the human Chediak-Higashi syndrome, a disease characterized by giant lysosomes in most cell types. In mice, treatment with androgenic hormones causes a 20-50-fold elevation in at least one kidney lysosomal enzyme, beta-glucuronidase. Beige mice treated with androgen had significantly higher kidney beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-D-glucosaminidase (hexosaminidase) levels than normal mice. Other androgen-inducible enzymes and enzyme markers for the cytosol, mitochondria, and peroxisomes were not increased in kidney of beige mice. No significant lysosomal enzyme elevation was observed in five other organs of beige mice with or without androgen treatment, nor in kidneys of beige females not treated with androgen. Histochemical staining for glucuronidase together with subcellular fractionation showed that the higher glucuronidase content of beige mouse kidney is caused by a striking accumulation of giant glucuronidase-containing lysosomes in tubule cells near the corticomedullary boundary. In normal mice lysosomal enzymes are coordinately released into the lumen of the kidney tubules and appreciable amounts of lysosomal enzymes are present in the urine. Levels of urinary lysosomal enzymes are much lower in beige mice than in normal mice. It appears that lysosomes may accumulate in beige mice because of defective exocytosis resulting either from decreased intracellular motility of lysosomes or from their improper fusion with the plasma membrane. A similar defect could account for characteristics of the Chediak-Higashi syndrome.", "contents": "Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi (beige) mice. The beige mouse is an animal model for the human Chediak-Higashi syndrome, a disease characterized by giant lysosomes in most cell types. In mice, treatment with androgenic hormones causes a 20-50-fold elevation in at least one kidney lysosomal enzyme, beta-glucuronidase. Beige mice treated with androgen had significantly higher kidney beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-D-glucosaminidase (hexosaminidase) levels than normal mice. Other androgen-inducible enzymes and enzyme markers for the cytosol, mitochondria, and peroxisomes were not increased in kidney of beige mice. No significant lysosomal enzyme elevation was observed in five other organs of beige mice with or without androgen treatment, nor in kidneys of beige females not treated with androgen. Histochemical staining for glucuronidase together with subcellular fractionation showed that the higher glucuronidase content of beige mouse kidney is caused by a striking accumulation of giant glucuronidase-containing lysosomes in tubule cells near the corticomedullary boundary. In normal mice lysosomal enzymes are coordinately released into the lumen of the kidney tubules and appreciable amounts of lysosomal enzymes are present in the urine. Levels of urinary lysosomal enzymes are much lower in beige mice than in normal mice. It appears that lysosomes may accumulate in beige mice because of defective exocytosis resulting either from decreased intracellular motility of lysosomes or from their improper fusion with the plasma membrane. A similar defect could account for characteristics of the Chediak-Higashi syndrome."}
{"id": "PMID:409", "title": "Stimulation of 2-deoxy-d-glucose transport in control and virus-transformed cells by ethidium bromide.", "content": "Recently we demonstrated that ethidium bromide altered the plasma and subcellular membrane glycoproteins in control and virus transformed cells. It is reported here that ethidium bromide also stimulated the membrane associated process of sugar transport. The KM of the virus transformed cells and the ethidium bromide treated cells is the same as that of the control cells while the maximum velocity as compared to the control cells is significantly increased. The transport of 2-deoxyl-D-glucose was inhibited by glucose, cytochalasin B and neuraminidase but was unaffected by variations in cell density or pH of the incubation medium.", "contents": "Stimulation of 2-deoxy-d-glucose transport in control and virus-transformed cells by ethidium bromide. Recently we demonstrated that ethidium bromide altered the plasma and subcellular membrane glycoproteins in control and virus transformed cells. It is reported here that ethidium bromide also stimulated the membrane associated process of sugar transport. The KM of the virus transformed cells and the ethidium bromide treated cells is the same as that of the control cells while the maximum velocity as compared to the control cells is significantly increased. The transport of 2-deoxyl-D-glucose was inhibited by glucose, cytochalasin B and neuraminidase but was unaffected by variations in cell density or pH of the incubation medium."}
{"id": "PMID:410", "title": "Effect of pharmacological agents on human keratinocyte mitosis in vitro. II. Inhibition by catecholamines.", "content": "Catecholamines produce mitotic inhibition in primary cell cultures of human keratinocytes probably via a block in the G2 part of the cell cycle. Epinephrine produced significant mitotic inhibition (49%) at a concentration as low as 4.5 X 10(-10) M, while its analog, isoproterenol, produced 47% inhibition at 1 X 10(-10) M. Norepinephrine elicited a 49% inhibitory response at 1 X 10(-8) M. One other catecholamine, dopamine, caused a 53% decrease in mitosis at 1 X 10(-6) M. Other structurally related amines to exhibit mitotic inhibition were phenylephrine, 58% at 1 X 10(-7) M; octopamine, 47% at 1 X 10(-5) M; and tyramine, 52% at 1 X 10(-4) M. Serotonin showed no mitotic inhibition at 1 X 10(-4) M. Various alpha and beta adrenergic blocking agents were added to the cell system. The alpha blocking agent, phentolamine, had no effect on mitosis. When added in conjunction with epinephrine or norepinephrine, no reduction of the catecholamine-induced mitotic inhibition was observed. The beta blocking agent, propranolol, by itself showed slight mitotic inhibition at 1 X 10(-6) M. When added along with epinephrine or noreinephrine, propranolol reduced the catecholamine-induced mitotic inhibition approximately 65%. In addition, propranolol blocked mitotic inhibition caused by phenylephrine, an alpha adrenergic agent. However, another beta blocking agent, dichloroisoproterenol, showed strong mitotic inhibition (53%) when added to the cultures at a concentration of 1 X 10(-8) M. The effect was reduced to zero in the presence of propranolol. These data suggest that while beta receptors may be involved in the catecholamine-induced mitotic inhibition of human keratinocytes in vitro, the nature of the receptor-molecule interaction may be complex.", "contents": "Effect of pharmacological agents on human keratinocyte mitosis in vitro. II. Inhibition by catecholamines. Catecholamines produce mitotic inhibition in primary cell cultures of human keratinocytes probably via a block in the G2 part of the cell cycle. Epinephrine produced significant mitotic inhibition (49%) at a concentration as low as 4.5 X 10(-10) M, while its analog, isoproterenol, produced 47% inhibition at 1 X 10(-10) M. Norepinephrine elicited a 49% inhibitory response at 1 X 10(-8) M. One other catecholamine, dopamine, caused a 53% decrease in mitosis at 1 X 10(-6) M. Other structurally related amines to exhibit mitotic inhibition were phenylephrine, 58% at 1 X 10(-7) M; octopamine, 47% at 1 X 10(-5) M; and tyramine, 52% at 1 X 10(-4) M. Serotonin showed no mitotic inhibition at 1 X 10(-4) M. Various alpha and beta adrenergic blocking agents were added to the cell system. The alpha blocking agent, phentolamine, had no effect on mitosis. When added in conjunction with epinephrine or norepinephrine, no reduction of the catecholamine-induced mitotic inhibition was observed. The beta blocking agent, propranolol, by itself showed slight mitotic inhibition at 1 X 10(-6) M. When added along with epinephrine or noreinephrine, propranolol reduced the catecholamine-induced mitotic inhibition approximately 65%. In addition, propranolol blocked mitotic inhibition caused by phenylephrine, an alpha adrenergic agent. However, another beta blocking agent, dichloroisoproterenol, showed strong mitotic inhibition (53%) when added to the cultures at a concentration of 1 X 10(-8) M. The effect was reduced to zero in the presence of propranolol. These data suggest that while beta receptors may be involved in the catecholamine-induced mitotic inhibition of human keratinocytes in vitro, the nature of the receptor-molecule interaction may be complex."}
{"id": "PMID:411", "title": "Serum-free growth of HTC cells containing glucocorticoid- and insulin-inducible tyrosine aminotransferase and cytoplasmic glucocorticoid receptors.", "content": "HTC cells have been made to grow in chemically defined medium without any macromolecular supplements whatsoever. Initial estimates of their relative amino acid requirements have been made. The cells grown in the defined medium retain many of the differentiated features which have been the focus of investigation in their serum-grown counterparts. Thus, the cells in defined medium contain cytoplasmic glucocorticoid receptors and have tyrosine aminotransferase which can be induced by glucocorticoids, serum or insulin. These cells also produce, in small amounts, an as yet undefined rat serum protein.", "contents": "Serum-free growth of HTC cells containing glucocorticoid- and insulin-inducible tyrosine aminotransferase and cytoplasmic glucocorticoid receptors. HTC cells have been made to grow in chemically defined medium without any macromolecular supplements whatsoever. Initial estimates of their relative amino acid requirements have been made. The cells grown in the defined medium retain many of the differentiated features which have been the focus of investigation in their serum-grown counterparts. Thus, the cells in defined medium contain cytoplasmic glucocorticoid receptors and have tyrosine aminotransferase which can be induced by glucocorticoids, serum or insulin. These cells also produce, in small amounts, an as yet undefined rat serum protein."}
{"id": "PMID:412", "title": "Stimulation of lactic acid production in chick embryo fibroblasts by serum and high pH in the absence of external glucose.", "content": "Lactic acid production by chick embryo fibroblasts occurs in the absence of exogenous glucose. Fifteen to 50-fold less lactic acid is formed in the absence of glucose than in its presence. Nevertheless, serum and pH stimulation enhances this residual lactic acid production to the same relative extent as when glucose is present. The amount of lactic acid formed cannot be accounted for by the catabolism of residual glucose in the medium since its concentration is less than one-tenth that of the lactic acid eventually produced. Moreover, the residual glucose concentration remains constant or increases during the course of the experiment. To a large extent lactic acid accumulation in the absence of external glucose is dependent on the presence of amino acids in the medium, but amino acid transport is not affected by the stimulatory agents used in this study. The results suggest that treatments which stimulate cell multiplication also activate those enzymatic pathways which convert amino acids to pyruvic and thence to lactic acid.", "contents": "Stimulation of lactic acid production in chick embryo fibroblasts by serum and high pH in the absence of external glucose. Lactic acid production by chick embryo fibroblasts occurs in the absence of exogenous glucose. Fifteen to 50-fold less lactic acid is formed in the absence of glucose than in its presence. Nevertheless, serum and pH stimulation enhances this residual lactic acid production to the same relative extent as when glucose is present. The amount of lactic acid formed cannot be accounted for by the catabolism of residual glucose in the medium since its concentration is less than one-tenth that of the lactic acid eventually produced. Moreover, the residual glucose concentration remains constant or increases during the course of the experiment. To a large extent lactic acid accumulation in the absence of external glucose is dependent on the presence of amino acids in the medium, but amino acid transport is not affected by the stimulatory agents used in this study. The results suggest that treatments which stimulate cell multiplication also activate those enzymatic pathways which convert amino acids to pyruvic and thence to lactic acid."}
{"id": "PMID:413", "title": "Isolation and studies of the granules of the amebocytes of Limulus polyphemus, the horseshoe crab.", "content": "Granules were isolated from the cytoplasm of the amebocytes of Limulus polyphemus, the horseshoe crab, by disruption of cells obtained from blood which had been drawn into 2 mM propranolol. The granules subsequently were purified by centrifugation through a sucrose gradient that contained heparin. Extracts of the granules were prepared by freezing and thawing the granule preparations in distilled water. Transmission and scanning electron microscopy of the granules revealed round or ovoid particles. However, only one type of granule appeared to be present. The ultraviolet spectrum of the extract of amebocyte granules demonstrated a peak at 277 nm at pH 7.4, and a shift into two peaks of 281 nm and 290 nm at alkaline pH. Analytical ultracentrifugation revealed a pattern similar to that observed with lysates prepared from intact amebocytes. Polyacrylamide gel electrophoresis, in the presence of urea at pH 4.5, demonstrated patterns similar to those observed with amebocyte lysate. Extracts of the granules were gelled by bacterial endotoxin. The blood of the horseshoe crab contains only one type of cell, the amebocyte. Previous studies have shown that the blood coagulation mechanism of Limulus is contained entirely within amebocytes. The current studies suggest that the granules, which pack the cytoplasm of these cells, contain all of the factors required for the coagulation of blood, including the clottable protein. The intracellularly localized coagulation system is released from amebocytes when their granules rupture during cell aggregation.", "contents": "Isolation and studies of the granules of the amebocytes of Limulus polyphemus, the horseshoe crab. Granules were isolated from the cytoplasm of the amebocytes of Limulus polyphemus, the horseshoe crab, by disruption of cells obtained from blood which had been drawn into 2 mM propranolol. The granules subsequently were purified by centrifugation through a sucrose gradient that contained heparin. Extracts of the granules were prepared by freezing and thawing the granule preparations in distilled water. Transmission and scanning electron microscopy of the granules revealed round or ovoid particles. However, only one type of granule appeared to be present. The ultraviolet spectrum of the extract of amebocyte granules demonstrated a peak at 277 nm at pH 7.4, and a shift into two peaks of 281 nm and 290 nm at alkaline pH. Analytical ultracentrifugation revealed a pattern similar to that observed with lysates prepared from intact amebocytes. Polyacrylamide gel electrophoresis, in the presence of urea at pH 4.5, demonstrated patterns similar to those observed with amebocyte lysate. Extracts of the granules were gelled by bacterial endotoxin. The blood of the horseshoe crab contains only one type of cell, the amebocyte. Previous studies have shown that the blood coagulation mechanism of Limulus is contained entirely within amebocytes. The current studies suggest that the granules, which pack the cytoplasm of these cells, contain all of the factors required for the coagulation of blood, including the clottable protein. The intracellularly localized coagulation system is released from amebocytes when their granules rupture during cell aggregation."}
{"id": "PMID:416", "title": "Purification of human red cell glucose 6-phosphate dehydrogenase by affinity chromatography.", "content": "Human glucose 6-phosphate dehydrogenase associated with NADPH was efficiently bound with agarose-bound NADP, whereas the enzyme associated with NADP was poorly bound with agarose-bound NADP. After the elimination of haemoglobin from haemolyzate by treatment with DEAE-cellulose, the enzyme was converted into the NADPH-bound form and was applied on an affinity column. The enzyme was specifically eluted from the column by NADP in the elution buffer. A homogeneous enzyme preparation was obtained in high yield.", "contents": "Purification of human red cell glucose 6-phosphate dehydrogenase by affinity chromatography. Human glucose 6-phosphate dehydrogenase associated with NADPH was efficiently bound with agarose-bound NADP, whereas the enzyme associated with NADP was poorly bound with agarose-bound NADP. After the elimination of haemoglobin from haemolyzate by treatment with DEAE-cellulose, the enzyme was converted into the NADPH-bound form and was applied on an affinity column. The enzyme was specifically eluted from the column by NADP in the elution buffer. A homogeneous enzyme preparation was obtained in high yield."}
{"id": "PMID:417", "title": "Simultaneous determination of propranolol and 4-hydroxypropranolol in plasma by mass fragmentography.", "content": "A quantitative method for the simultaneous determination of propranolol and its active metabolite 4-hydroxypropranolol in human plasma is described. Plasma samples are extracted at pH 9.6 with ethyl acetate after the addition of sodium bisulphite and the internal standard oxprenolol. The extracts are derivatized with trifluoroacetic anhydride before separation on a gas chromatograph--mass spectrometer. Detection and quantitation of the trifluoroacetyl derivatives are made by single-ion monitoring. The minimum detectable concentration of propranolol is 1 ng/ml and of 4-hydroxypropranolol 5 ng/ml using 1-ml plasma samples. No interferences from normal plasma constituents or from drugs commonly prescribed together with propranolol were detected.", "contents": "Simultaneous determination of propranolol and 4-hydroxypropranolol in plasma by mass fragmentography. A quantitative method for the simultaneous determination of propranolol and its active metabolite 4-hydroxypropranolol in human plasma is described. Plasma samples are extracted at pH 9.6 with ethyl acetate after the addition of sodium bisulphite and the internal standard oxprenolol. The extracts are derivatized with trifluoroacetic anhydride before separation on a gas chromatograph--mass spectrometer. Detection and quantitation of the trifluoroacetyl derivatives are made by single-ion monitoring. The minimum detectable concentration of propranolol is 1 ng/ml and of 4-hydroxypropranolol 5 ng/ml using 1-ml plasma samples. No interferences from normal plasma constituents or from drugs commonly prescribed together with propranolol were detected."}
{"id": "PMID:418", "title": "High pressure liquid chromatography on cannabis. Identification of separated constituents.", "content": "Delta9-and-delta8-Tetrahydrocannabinol, delta9-tetrahydrocannabinolic acid, cannabidiol, cannabidolic acid, cannabinol, cannabinolic acid, cannabichromene and cannabichromenic acid were located in the liquid chromatogram of cannabis. Identifications were confirmed by gas chromatography-mass spectrometry.", "contents": "High pressure liquid chromatography on cannabis. Identification of separated constituents. Delta9-and-delta8-Tetrahydrocannabinol, delta9-tetrahydrocannabinolic acid, cannabidiol, cannabidolic acid, cannabinol, cannabinolic acid, cannabichromene and cannabichromenic acid were located in the liquid chromatogram of cannabis. Identifications were confirmed by gas chromatography-mass spectrometry."}
{"id": "PMID:419", "title": "Amino acid analysis by ion-exchange chromatography using a lithium elution gradient. Influence of methanol concentration and sample pH.", "content": "The separation of amino acids has been achieved on a short column of Chromo-Beads C2 resin, with a lithium gradient-elution system. The analysis took 8 h. The separation of asparagine and glutamine from glutamic acid was highly dependent on the sample pH and on the methanol concentration in the first buffer of the gradient. The method has been applied to analysis of human plasma and granulocytes for amino acids.", "contents": "Amino acid analysis by ion-exchange chromatography using a lithium elution gradient. Influence of methanol concentration and sample pH. The separation of amino acids has been achieved on a short column of Chromo-Beads C2 resin, with a lithium gradient-elution system. The analysis took 8 h. The separation of asparagine and glutamine from glutamic acid was highly dependent on the sample pH and on the methanol concentration in the first buffer of the gradient. The method has been applied to analysis of human plasma and granulocytes for amino acids."}
{"id": "PMID:420", "title": "Determination of 3-(5-tetrazolyl) thioxanthone 10,10-dioxide in human plasma, urine and faeces.", "content": "A gas chromatographic method is described for assay of 3-(5-tetrazolyl) thioxanthone 10,10-dioxide (BW 59C) in human plasma, urine and faeces. After extraction into 1,2-dichloroethane from alkaline medium the compound is converted to the heptafluorobutyrate derivative which is injected into a gas chromatograph and measured using a 63Ni electron capture detector. The assay produces a linear calibration curve over the range 0-30 mug/ml when the internal standard method is used. Reproducibility is good and sensitivity down to 1 ng injected on column is possible. The method has been used to investigate the pharmacokinetic properties of BW 59C in man and has been semi-automated by the use of an autosampler and dedicated computer.", "contents": "Determination of 3-(5-tetrazolyl) thioxanthone 10,10-dioxide in human plasma, urine and faeces. A gas chromatographic method is described for assay of 3-(5-tetrazolyl) thioxanthone 10,10-dioxide (BW 59C) in human plasma, urine and faeces. After extraction into 1,2-dichloroethane from alkaline medium the compound is converted to the heptafluorobutyrate derivative which is injected into a gas chromatograph and measured using a 63Ni electron capture detector. The assay produces a linear calibration curve over the range 0-30 mug/ml when the internal standard method is used. Reproducibility is good and sensitivity down to 1 ng injected on column is possible. The method has been used to investigate the pharmacokinetic properties of BW 59C in man and has been semi-automated by the use of an autosampler and dedicated computer."}
{"id": "PMID:421", "title": "Methods to improve detection of pneumococci in respiratory secretions.", "content": "Simple methods to enhance the detection of pneumococci in respiratory secretions are needed. Sheep blood agar containing 5 mug of gentamicin per ml was more often positive (89%) than either standard sheep blood agar (54%) or mouse inoculation (65%) in recovering pneumococci from 62 adult and pediatric patients. In adults, the direct quellung test on sputum smear was a rapid, sensitive method for predicting subsequent pneumococcal isolation by culture (19 of 20 patients, 95%). The quellung test and gentamicin plate show improved sensitivity over current techniques for pneumococcal detection and can be recommended for general use.", "contents": "Methods to improve detection of pneumococci in respiratory secretions. Simple methods to enhance the detection of pneumococci in respiratory secretions are needed. Sheep blood agar containing 5 mug of gentamicin per ml was more often positive (89%) than either standard sheep blood agar (54%) or mouse inoculation (65%) in recovering pneumococci from 62 adult and pediatric patients. In adults, the direct quellung test on sputum smear was a rapid, sensitive method for predicting subsequent pneumococcal isolation by culture (19 of 20 patients, 95%). The quellung test and gentamicin plate show improved sensitivity over current techniques for pneumococcal detection and can be recommended for general use."}
{"id": "PMID:422", "title": "Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.", "content": "The dose dependence of the acute effects of ethanol upon liver intermediary metabolism in vivo has been demonstrated in rats. Ethanol was given i.p. in doses of 0.69, 1.7, and 3.0 g/kg in equal volumes (20 ml/kg). The liver was freeze-clamped 120 min after injection, and multiple metabolites were measured in the perchloric acid extract of the tissue. Each group showed a significantly different pattern of metabolites, redox states, and phosphorylation potentials although the rate of ethanol disappearance, at least between the two highest dose groups, was not significantly different. The mitochondrial free [NAD+]/[NADH] ratios and the cytoplasmic free [NADP+]/[NADPH] ratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphorylation potential ([ATP]/[ADP][P1]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups. The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production.", "contents": "Dependence on dose of the acute effects of ethanol on liver metabolism in vivo. The dose dependence of the acute effects of ethanol upon liver intermediary metabolism in vivo has been demonstrated in rats. Ethanol was given i.p. in doses of 0.69, 1.7, and 3.0 g/kg in equal volumes (20 ml/kg). The liver was freeze-clamped 120 min after injection, and multiple metabolites were measured in the perchloric acid extract of the tissue. Each group showed a significantly different pattern of metabolites, redox states, and phosphorylation potentials although the rate of ethanol disappearance, at least between the two highest dose groups, was not significantly different. The mitochondrial free [NAD+]/[NADH] ratios and the cytoplasmic free [NADP+]/[NADPH] ratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphorylation potential ([ATP]/[ADP][P1]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups. The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production."}
{"id": "PMID:423", "title": "Factors affecting the solubility of calcium pyrophosphate dihydrate crystals.", "content": "The solubility of triclinic calcium pyrophosphate dihydrate (CPPD) crystals was measured under varying conditions using 45Ca-labeled crystals, expressing solubility as micromoles per liter of 45Ca in solution. In a 0.1-M Tris-HC1 buffer pH 7.4, the solubility of accurately sized CPPD crystals (37-20mum) was 60muM with maximal solubility being attained after about 8 h incubation at 37degreeC. Reduction in crystal size, decrease in pH, increase in ionic strength, Mg++, citrate, and albumin all increased solubility. The most marked effects on solubility occurred when changing the calcium concentration or by enzymatic hydrolysis of inoganic pyrophosphate to orthophosphate. It was found that decreasing the ionized calcium level below 5 mg/100 ml resulted in a progressive enhancement of solubility. The observed solubility-enhancing effects of albumin could be explained solely on its calcium-binding ability and thereby, altered ionized calcium level. Diffusible calcium in synovial fluid was only 40% of the total calcium concentration, which means most joint fluids are normally near the critical concentration of 5 mg/100 ml of ionized calcium, below which solubility is enhanced. During surgery, especially parathyroidectomy, calcium levels fall, favoring dissolution of CPPD crystals. We speculate that the slight decrease in crystal size during dissolution frees them from their cartilaginous mold, resulting in a dose-dependent inflammatory reaction as they are \"shed\" into the joint space. Crystal shedding may be reinforced by the modest fall in joint fluid pH accompanying the inflammatory response.", "contents": "Factors affecting the solubility of calcium pyrophosphate dihydrate crystals. The solubility of triclinic calcium pyrophosphate dihydrate (CPPD) crystals was measured under varying conditions using 45Ca-labeled crystals, expressing solubility as micromoles per liter of 45Ca in solution. In a 0.1-M Tris-HC1 buffer pH 7.4, the solubility of accurately sized CPPD crystals (37-20mum) was 60muM with maximal solubility being attained after about 8 h incubation at 37degreeC. Reduction in crystal size, decrease in pH, increase in ionic strength, Mg++, citrate, and albumin all increased solubility. The most marked effects on solubility occurred when changing the calcium concentration or by enzymatic hydrolysis of inoganic pyrophosphate to orthophosphate. It was found that decreasing the ionized calcium level below 5 mg/100 ml resulted in a progressive enhancement of solubility. The observed solubility-enhancing effects of albumin could be explained solely on its calcium-binding ability and thereby, altered ionized calcium level. Diffusible calcium in synovial fluid was only 40% of the total calcium concentration, which means most joint fluids are normally near the critical concentration of 5 mg/100 ml of ionized calcium, below which solubility is enhanced. During surgery, especially parathyroidectomy, calcium levels fall, favoring dissolution of CPPD crystals. We speculate that the slight decrease in crystal size during dissolution frees them from their cartilaginous mold, resulting in a dose-dependent inflammatory reaction as they are \"shed\" into the joint space. Crystal shedding may be reinforced by the modest fall in joint fluid pH accompanying the inflammatory response."}
{"id": "PMID:425", "title": "Evidence from rats that morphine tolerance is a learned response.", "content": "It is proposed that the direct analgesic effect of morphine becomes attenuated over the course of successive administrations of the narcotic by a conditioned, compensatory, hyperalgesic response elicited by the administration procedure, the net result being analgesic tolerance. Using the \"hot plate\" analgesia assessment situation with rats, this conditioning view of tolerance is supported by several findings: (a) It is necessary to have reliable environmental cues predicting the systemic effects of morphine if tolerance is to be observed, (b) a hyperalgesic conditioned response may be observed in morphine-tolerant subjects when drug administration cues are followed by a placebo, and (c) merely by repeatedly presenting environmental cues previously associated with morphine (but now presented with a placebo), morphine tolerance can be extinguished.", "contents": "Evidence from rats that morphine tolerance is a learned response. It is proposed that the direct analgesic effect of morphine becomes attenuated over the course of successive administrations of the narcotic by a conditioned, compensatory, hyperalgesic response elicited by the administration procedure, the net result being analgesic tolerance. Using the \"hot plate\" analgesia assessment situation with rats, this conditioning view of tolerance is supported by several findings: (a) It is necessary to have reliable environmental cues predicting the systemic effects of morphine if tolerance is to be observed, (b) a hyperalgesic conditioned response may be observed in morphine-tolerant subjects when drug administration cues are followed by a placebo, and (c) merely by repeatedly presenting environmental cues previously associated with morphine (but now presented with a placebo), morphine tolerance can be extinguished."}
{"id": "PMID:426", "title": "Murexide for determination of free and protein-bound calcium in model systems.", "content": "The determination with murexide of free and protein-bound calcium in model systems of known composition, ionic strength, and pH was investigated. The spectra of calcium murexide in the presence of varying amounts of calcium ions indicated that the absorption maximum fo calcium murexide complex occurs at 480 nm while that of murexide ion is at 520 nm. The absorbance at 509 nm is independent of calcium ion concentration and, therefore, could be used to measure the total dye. The spectra are pH dependent but constant in the range 6.5 to 7.0. The apparent dissociation constant of calcium murexide is dependent upon ionic environment, ionic strength, and free calcium ion concentration. The relationship between the apparent dissociation constant and free calcium concentration was established. Whole casein had no effect on the absorption spectra of calcium murexide and no affinity for calcium murexide complex or murexide ion. Beta-casein, at the concentrations employed, did not influence the dissociation fo calcium murexide. At pH 7.0, ionic strength .1, and 2 C, Beta-casein bound calcium as if there were 8.65 binding sites per molecule, each of pK 2.23, corresponding to an intrinsic association constant of 168.9 liters per mole.", "contents": "Murexide for determination of free and protein-bound calcium in model systems. The determination with murexide of free and protein-bound calcium in model systems of known composition, ionic strength, and pH was investigated. The spectra of calcium murexide in the presence of varying amounts of calcium ions indicated that the absorption maximum fo calcium murexide complex occurs at 480 nm while that of murexide ion is at 520 nm. The absorbance at 509 nm is independent of calcium ion concentration and, therefore, could be used to measure the total dye. The spectra are pH dependent but constant in the range 6.5 to 7.0. The apparent dissociation constant of calcium murexide is dependent upon ionic environment, ionic strength, and free calcium ion concentration. The relationship between the apparent dissociation constant and free calcium concentration was established. Whole casein had no effect on the absorption spectra of calcium murexide and no affinity for calcium murexide complex or murexide ion. Beta-casein, at the concentrations employed, did not influence the dissociation fo calcium murexide. At pH 7.0, ionic strength .1, and 2 C, Beta-casein bound calcium as if there were 8.65 binding sites per molecule, each of pK 2.23, corresponding to an intrinsic association constant of 168.9 liters per mole."}
{"id": "PMID:424", "title": "Lorazepam compared with pentobarbital for nighttime sedation.", "content": "Lorazepam (0.5, 1, 2, and 4 mg) was compared with pentobarbital (60 and 180 mg) for its effect on sleep in \"hospital insomnia.\" Subjective-response data were collected by research nurses. Lorazepam was found to be a potent nighttime sedative: 1 to 1.25 mg of lorazepam is equivalent to 100 mg sodium pentobarbital for measures of sleep quality and duration. At this dose level it is less effective than 100 mg of pentobarbital as a sleep inducer. Studies at higher doses (up to 4 mg) indicate that lorazepam has a wide therapeutic index.", "contents": "Lorazepam compared with pentobarbital for nighttime sedation. Lorazepam (0.5, 1, 2, and 4 mg) was compared with pentobarbital (60 and 180 mg) for its effect on sleep in \"hospital insomnia.\" Subjective-response data were collected by research nurses. Lorazepam was found to be a potent nighttime sedative: 1 to 1.25 mg of lorazepam is equivalent to 100 mg sodium pentobarbital for measures of sleep quality and duration. At this dose level it is less effective than 100 mg of pentobarbital as a sleep inducer. Studies at higher doses (up to 4 mg) indicate that lorazepam has a wide therapeutic index."}
{"id": "PMID:429", "title": "Effect of trace elements on dissolution of hydroxyapatite by cariogenic streptococci.", "content": "The effect of low levels of strontium, boron, lithium, molybdenum, and fluorine, alone and in combination, on hydroxyapatite solubility, bacterial growth, and acid production in five antigenic types of Streptococcus mutans was investigated. Pour plates containing synthetic hydroxyapatite were used to compare dissolution of hydroxyapatite. The colonies of the five antigenic types of S mutans produced zones of dissolution that were measured. Acid production and growth were studied in broth culture media. The results show that low levels of strontium and fluorine can significantly reduce demineralization of synthetic hydroxyapatite by S mutans in vitro.", "contents": "Effect of trace elements on dissolution of hydroxyapatite by cariogenic streptococci. The effect of low levels of strontium, boron, lithium, molybdenum, and fluorine, alone and in combination, on hydroxyapatite solubility, bacterial growth, and acid production in five antigenic types of Streptococcus mutans was investigated. Pour plates containing synthetic hydroxyapatite were used to compare dissolution of hydroxyapatite. The colonies of the five antigenic types of S mutans produced zones of dissolution that were measured. Acid production and growth were studied in broth culture media. The results show that low levels of strontium and fluorine can significantly reduce demineralization of synthetic hydroxyapatite by S mutans in vitro."}
{"id": "PMID:439", "title": "[Use of isotopes in the diagnosis of malignant breast tumors].", "content": "The authors, with 67 Gallium, have obtained positive scintigraphy of the breast only in cases of carcinoma. Reliability of negative scintigraphy however is less good. Isotopic investigation of the bones is important in breast cancer and reveal early osseous metastasis.", "contents": "[Use of isotopes in the diagnosis of malignant breast tumors]. The authors, with 67 Gallium, have obtained positive scintigraphy of the breast only in cases of carcinoma. Reliability of negative scintigraphy however is less good. Isotopic investigation of the bones is important in breast cancer and reveal early osseous metastasis."}
{"id": "PMID:440", "title": "Peroxisome development in the metanephric kidney of mouse.", "content": "The relationship of enzymatic activity to organelle development and organelle number during differentiation of the metanephric kidney in the mouse was approached from several experimental directions. Biochemical analyses of marker enzymes for peroxisomes (catalase and D-amino acid oxidase), mitochondria (cytochrome oxidase) and lysosomes (acid phosphatase) were performed on kidneys at ages from 17 days prenatal to adult. These data were correlated with a morphometric analysis of populations of peroxisomes and mitochondria in differentiating cells of the proximal tubule. Postnatal development of the metanephric kidney was found to be accompanied by a rapid increase in both the specific activity of catalase and the number of peroxisomes per 100 mu2 in the proximal tubule during the first 4 weeks of postnatal growth. Elaboration of the endoplasmic reticulum (ER) was seen to parallel the increase in number of peroxisomes to which segments of ER were often in close apposition. Extensive interactions between segments of ER and peroxisomes were readily visible in 0.5-mu sections viewed in the high voltage electron microscope. In contrast to peroxisomes, neither mitochondria nor lysosomes followed a similar pattern of net organelle increase, suggesting that a defined population density of mitochondria and lysosomes may exist in the proximal tubule at birth, prior to complete development of the kidney.", "contents": "Peroxisome development in the metanephric kidney of mouse. The relationship of enzymatic activity to organelle development and organelle number during differentiation of the metanephric kidney in the mouse was approached from several experimental directions. Biochemical analyses of marker enzymes for peroxisomes (catalase and D-amino acid oxidase), mitochondria (cytochrome oxidase) and lysosomes (acid phosphatase) were performed on kidneys at ages from 17 days prenatal to adult. These data were correlated with a morphometric analysis of populations of peroxisomes and mitochondria in differentiating cells of the proximal tubule. Postnatal development of the metanephric kidney was found to be accompanied by a rapid increase in both the specific activity of catalase and the number of peroxisomes per 100 mu2 in the proximal tubule during the first 4 weeks of postnatal growth. Elaboration of the endoplasmic reticulum (ER) was seen to parallel the increase in number of peroxisomes to which segments of ER were often in close apposition. Extensive interactions between segments of ER and peroxisomes were readily visible in 0.5-mu sections viewed in the high voltage electron microscope. In contrast to peroxisomes, neither mitochondria nor lysosomes followed a similar pattern of net organelle increase, suggesting that a defined population density of mitochondria and lysosomes may exist in the proximal tubule at birth, prior to complete development of the kidney."}
{"id": "PMID:442", "title": "Inhibitory effects of antihistamines and antiserotonins on the bone marrow reactions produced by Escherichia coli endotoxin in mice.", "content": "The bone marrow reactions (that is, decrease of nucleated cell counts and increase of red blood cell counts) of mouse bone were observed 1 hr after injection of endotoxin and peaked after 18 hr. These reactions were significantly inhibited when diphenhydramine, promethazine (antihistamines), chlorpromazine (antiserotonin), or cyproheptadine (antihistamine and antiserotonin) was given 30 min before endotoxin. Such bone marrow reactions were also induced with histamine or serotonin and peaked 1 hr after administration. The histamine-induced changes were inhibited by prior treatment with diphenhydramine. These reactions were also produced by injection of a small amount of both histamine and serotonin, whereas no change was found when mice were given a single injection of a larger dose of histamine or serotonin. These results indicate that histamine and serotonin released in mice at the initial stage after endotoxin synergistically trigger the bone marrow reactions, which then continue in the presence of further mediators. Antihistamines and antiserotonins are considered to hinder the whole process of reactions produced by endotoxin.", "contents": "Inhibitory effects of antihistamines and antiserotonins on the bone marrow reactions produced by Escherichia coli endotoxin in mice. The bone marrow reactions (that is, decrease of nucleated cell counts and increase of red blood cell counts) of mouse bone were observed 1 hr after injection of endotoxin and peaked after 18 hr. These reactions were significantly inhibited when diphenhydramine, promethazine (antihistamines), chlorpromazine (antiserotonin), or cyproheptadine (antihistamine and antiserotonin) was given 30 min before endotoxin. Such bone marrow reactions were also induced with histamine or serotonin and peaked 1 hr after administration. The histamine-induced changes were inhibited by prior treatment with diphenhydramine. These reactions were also produced by injection of a small amount of both histamine and serotonin, whereas no change was found when mice were given a single injection of a larger dose of histamine or serotonin. These results indicate that histamine and serotonin released in mice at the initial stage after endotoxin synergistically trigger the bone marrow reactions, which then continue in the presence of further mediators. Antihistamines and antiserotonins are considered to hinder the whole process of reactions produced by endotoxin."}
{"id": "PMID:446", "title": "On the interactions between pancreatic lipase and colipase and the substrate, and the importance of bile salts.", "content": "The interactions between pancreatic lipase and colipase and the substrate and the effect of bile salts on these interactions have been investigated by the use of kinetic experiments and studies on the semiquantitative phase distribution of lipase and colipase activities. The results suggest that lipase binds to hydrophobic interfaces with partial irreversible inactivation. Bile salts in the range of micellar concentrations and above a pH of about 6.5 displace lipase from this binding, resulting in a reversible in activation. At pH values below about 6.5, lipase binds strongly to the substrate even in the presence of bile salt, and a low activity peak is seen around pH 5.5. This is the result of the binding of lipase to the \"supersubstrate\" and the activity of the catalytic site. In the presence of bile salt, colipase promotes the binding of lipase to the \"supersubstrate\" but not to other hydrophobic interfaces, and catalytic activity is reestablished. Kinetic data indicate that the binding between colipase and lipase in the presence of substrate is strong and occurs in an approximately stoichiometric relationship.", "contents": "On the interactions between pancreatic lipase and colipase and the substrate, and the importance of bile salts. The interactions between pancreatic lipase and colipase and the substrate and the effect of bile salts on these interactions have been investigated by the use of kinetic experiments and studies on the semiquantitative phase distribution of lipase and colipase activities. The results suggest that lipase binds to hydrophobic interfaces with partial irreversible inactivation. Bile salts in the range of micellar concentrations and above a pH of about 6.5 displace lipase from this binding, resulting in a reversible in activation. At pH values below about 6.5, lipase binds strongly to the substrate even in the presence of bile salt, and a low activity peak is seen around pH 5.5. This is the result of the binding of lipase to the \"supersubstrate\" and the activity of the catalytic site. In the presence of bile salt, colipase promotes the binding of lipase to the \"supersubstrate\" but not to other hydrophobic interfaces, and catalytic activity is reestablished. Kinetic data indicate that the binding between colipase and lipase in the presence of substrate is strong and occurs in an approximately stoichiometric relationship."}
{"id": "PMID:447", "title": "Effect of ionic strength and ionic composition of assay buffers on the interaction of thyroxine with plasma proteins.", "content": "When plasma proteins are diluted with buffer the ionic strength and ionic composition of that buffer affects the interactions between thyroxine (T4) and its plasma protein-binding sites. Increases in phosphate, chloride or barbiturate ion concentration from 50 to 200 mmol/l caused a significant decrease in the affinity of plasma proteins for T4, and a concurrent increase in the concentration of unbound T4. These results cannot be completely accounted for by changes in ionic strength since at the same ionic strength different anions caused quantitatively different effects on unbound T4 concentration. The degree of depression of T4 binding by the three anions studied was in the order barbiturate greater than chloride greater than phosphate. The results of a systematic study on the composition of diluent buffer systems indicated that when a 50 mM-sodium phosphate-100 mM-NaCl buffer (pH 7-4) was used as a plasma diluent, there were unlikely to be gross changes in the T4-binding properties of plasma proteins with dilution.", "contents": "Effect of ionic strength and ionic composition of assay buffers on the interaction of thyroxine with plasma proteins. When plasma proteins are diluted with buffer the ionic strength and ionic composition of that buffer affects the interactions between thyroxine (T4) and its plasma protein-binding sites. Increases in phosphate, chloride or barbiturate ion concentration from 50 to 200 mmol/l caused a significant decrease in the affinity of plasma proteins for T4, and a concurrent increase in the concentration of unbound T4. These results cannot be completely accounted for by changes in ionic strength since at the same ionic strength different anions caused quantitatively different effects on unbound T4 concentration. The degree of depression of T4 binding by the three anions studied was in the order barbiturate greater than chloride greater than phosphate. The results of a systematic study on the composition of diluent buffer systems indicated that when a 50 mM-sodium phosphate-100 mM-NaCl buffer (pH 7-4) was used as a plasma diluent, there were unlikely to be gross changes in the T4-binding properties of plasma proteins with dilution."}
{"id": "PMID:448", "title": "The innervation of the salivary gland of the moth, Manduca sexta: evidence that dopamine is the transmitter.", "content": "1. Using the Falck-Hillarp histochemical technique for monoamines, evidence was found for the presence of a catecholamine in the salivary gland nerves of the moth, Manduca sexta. 2. The innervation was studied with the electron microscope. Only the fluid-secreting region of the gland is innervated and the nerve endings are characteristic of monoamine-containing terminals. 3. Using a sensitive enzymatic-isotopic assay for catecholamines, it was found that whole salivary glands contain 0.33 mug/g dopamine but no noradrenaline. 4. It seems likely that dopamine mediates fluid-secretion in the salivary gland of Manduca as it does a number of other arthropods.", "contents": "The innervation of the salivary gland of the moth, Manduca sexta: evidence that dopamine is the transmitter. 1. Using the Falck-Hillarp histochemical technique for monoamines, evidence was found for the presence of a catecholamine in the salivary gland nerves of the moth, Manduca sexta. 2. The innervation was studied with the electron microscope. Only the fluid-secreting region of the gland is innervated and the nerve endings are characteristic of monoamine-containing terminals. 3. Using a sensitive enzymatic-isotopic assay for catecholamines, it was found that whole salivary glands contain 0.33 mug/g dopamine but no noradrenaline. 4. It seems likely that dopamine mediates fluid-secretion in the salivary gland of Manduca as it does a number of other arthropods."}
{"id": "PMID:449", "title": "An electrophysiological analysis of chemoreception in the sea anemone Tealia felina.", "content": "1. Electrophysiological techniques have been employed to examine the nature of the response observed in the ectodermal slow-conduction system (SSI) when dissolved food substances contact the column of Tealia felina. The response seems to consist entirely of sensory activity which may continue for periods of many minutes, provided that the stimulatory chemicals remain contacting the column. 2. The interval between each evoked pulse gradually increases as the sensory response progresses. This does not result from fatigue in the conduction system but involves a genuine process of sensory adaptation. This may occur over a period of several minutes, which is much longer than comparable adaptation in higher animals. 3. Physiological evidence suggests that the chemoreceptors involved are dispersed throughout the column ectoderm and are absent from the pedal disc, oral disc, tentacles and pharynx. 4. The basic role of the SSI in coordinating behavioural activity in sea anemones is reviewed. It is concluded that it functions primarily as a single, diffuse-conducting unit responsible for transmitting frequency-coded sensory information from ectodermal chemoreceptors to ectodermal (and perhaps endodermal) effectors.", "contents": "An electrophysiological analysis of chemoreception in the sea anemone Tealia felina. 1. Electrophysiological techniques have been employed to examine the nature of the response observed in the ectodermal slow-conduction system (SSI) when dissolved food substances contact the column of Tealia felina. The response seems to consist entirely of sensory activity which may continue for periods of many minutes, provided that the stimulatory chemicals remain contacting the column. 2. The interval between each evoked pulse gradually increases as the sensory response progresses. This does not result from fatigue in the conduction system but involves a genuine process of sensory adaptation. This may occur over a period of several minutes, which is much longer than comparable adaptation in higher animals. 3. Physiological evidence suggests that the chemoreceptors involved are dispersed throughout the column ectoderm and are absent from the pedal disc, oral disc, tentacles and pharynx. 4. The basic role of the SSI in coordinating behavioural activity in sea anemones is reviewed. It is concluded that it functions primarily as a single, diffuse-conducting unit responsible for transmitting frequency-coded sensory information from ectodermal chemoreceptors to ectodermal (and perhaps endodermal) effectors."}
{"id": "PMID:450", "title": "The selective eosinophil chemotactic activity of histamine.", "content": "Histamine diphosphate was shown to selectively attract human eosinophils from mixed granulocyte populations when over 20% eosinophils were used in a modified Boyden chamber chemotactic assay system. This effect of histamine is abolished by incubation with diamine oxidase (histaminase) and was generated by decarboxylation of L-histidine. A linear dose dependent increase in eosinophil migration was observed between 3 X 10(-7) M and 1.25 X 10(-6) M, while higher concentrations of histamine inhibited the migration of eosinophils. The attractant activity of histamine was not inhibited by H-1 or H-2 receptor antagonists, however, the inhibition of migration observed at higher histamine concentrations was reversed by metiamine, an H-2 receptor antagonist. The effects of histamine upon eosinophil migration were demonstrable using three different assays: (a) counting cells that had traversed 5-mum pore, 12-mum thick polycarbonate filters, (b) counting cells that had migrated various distances into a 3-mum pore, 145-mum cellulose nitrate filters, or (c) measuring the number of cells that had traversed an upper polycarbonate filter and migrated into a lower cellulose nitrate filter using 15Cr-labeled cells. The ability of histamine to enhance eosinophil migration was shown to be dependent upon the presence of a concentration gradient; histamine did not cause a dose-dependent increase in random motility. Furthermore, preincubation of the eosinophils with histamine deactivate the cells to further stimulation by histamine or by C5a. It is concluded that in low doses histamine is a chemoattractant for human eosinophils, while in higher doses histamine inhibits eosinophil migration. These observations may relate to the influx and localization of eosinophils in immediate hypersensitivity reactions.", "contents": "The selective eosinophil chemotactic activity of histamine. Histamine diphosphate was shown to selectively attract human eosinophils from mixed granulocyte populations when over 20% eosinophils were used in a modified Boyden chamber chemotactic assay system. This effect of histamine is abolished by incubation with diamine oxidase (histaminase) and was generated by decarboxylation of L-histidine. A linear dose dependent increase in eosinophil migration was observed between 3 X 10(-7) M and 1.25 X 10(-6) M, while higher concentrations of histamine inhibited the migration of eosinophils. The attractant activity of histamine was not inhibited by H-1 or H-2 receptor antagonists, however, the inhibition of migration observed at higher histamine concentrations was reversed by metiamine, an H-2 receptor antagonist. The effects of histamine upon eosinophil migration were demonstrable using three different assays: (a) counting cells that had traversed 5-mum pore, 12-mum thick polycarbonate filters, (b) counting cells that had migrated various distances into a 3-mum pore, 145-mum cellulose nitrate filters, or (c) measuring the number of cells that had traversed an upper polycarbonate filter and migrated into a lower cellulose nitrate filter using 15Cr-labeled cells. The ability of histamine to enhance eosinophil migration was shown to be dependent upon the presence of a concentration gradient; histamine did not cause a dose-dependent increase in random motility. Furthermore, preincubation of the eosinophils with histamine deactivate the cells to further stimulation by histamine or by C5a. It is concluded that in low doses histamine is a chemoattractant for human eosinophils, while in higher doses histamine inhibits eosinophil migration. These observations may relate to the influx and localization of eosinophils in immediate hypersensitivity reactions."}
{"id": "PMID:451", "title": "Hemoglobins and hemocyanins: comparative aspects of structure and function.", "content": "Comparative studies of protein structure and function can be quite interesting by themselves, and even more interesting when interpreted with respect to an animal's physiology. In the case of fish hemoglobins, some success in the latter has been achieved but there are still many unsolved problems. It appears that comparative physiology and biochemistry have entered an era where results from comparative studies can shed a great deal of light on biochemical mechanisms in general. The trout hemoglobin system is an example. Distinctive hemoglobins in this system are presently being used as high resolution probes of the ligand-binding mechanism. Characterization of the multiple, structurally distinct subunits of the 60S Limulus hemocyanin molecule may similarly aid in understanding its function. Our studies suggest the possibility of using Limulus hemocyanin and other hemocyanins as structural homologs and analogs of more complex macromolecular arrays. The rapid development of molecular structural data from X-ray crystallographers combined with the vast data of comparative physiology and biochemistry makes this one of the most exciting areas in present day science.", "contents": "Hemoglobins and hemocyanins: comparative aspects of structure and function. Comparative studies of protein structure and function can be quite interesting by themselves, and even more interesting when interpreted with respect to an animal's physiology. In the case of fish hemoglobins, some success in the latter has been achieved but there are still many unsolved problems. It appears that comparative physiology and biochemistry have entered an era where results from comparative studies can shed a great deal of light on biochemical mechanisms in general. The trout hemoglobin system is an example. Distinctive hemoglobins in this system are presently being used as high resolution probes of the ligand-binding mechanism. Characterization of the multiple, structurally distinct subunits of the 60S Limulus hemocyanin molecule may similarly aid in understanding its function. Our studies suggest the possibility of using Limulus hemocyanin and other hemocyanins as structural homologs and analogs of more complex macromolecular arrays. The rapid development of molecular structural data from X-ray crystallographers combined with the vast data of comparative physiology and biochemistry makes this one of the most exciting areas in present day science."}
{"id": "PMID:452", "title": "How do biological systems discriminate among physically similar ions?", "content": "This paper reviews the history of understanding how biological systems can discriminate so strikingly among physically similar ions, especially alkali cations. Appreciation of qualitative regularities (\"permitted sequences\") and quantitative regularities (\"selectivity isotherms\") in ion selectivity grew first from studies of ion exchangers and glass electrodes, then of biological systems such as enzymes and cell membranes, and most recently of lipid bilayers doped with model pores and carriers. Discrimination of ions depends on both electrostatic and steric forces. \"Black-box\" studies on intact biological membranes have in some cases yielded molecular clues to the structure of the actual biological pores and carriers. Major current problems involve the extraction of these molecules; how to do it, what to do when it is achieved, and how (and if) it is relevant to the central problems of membrane function. Further advances are expected soon from studies of rate barriers within membranes, of voltage-dependent (\"excitable\") conducting channels, and of increasingly complex model systems and biological membranes.", "contents": "How do biological systems discriminate among physically similar ions? This paper reviews the history of understanding how biological systems can discriminate so strikingly among physically similar ions, especially alkali cations. Appreciation of qualitative regularities (\"permitted sequences\") and quantitative regularities (\"selectivity isotherms\") in ion selectivity grew first from studies of ion exchangers and glass electrodes, then of biological systems such as enzymes and cell membranes, and most recently of lipid bilayers doped with model pores and carriers. Discrimination of ions depends on both electrostatic and steric forces. \"Black-box\" studies on intact biological membranes have in some cases yielded molecular clues to the structure of the actual biological pores and carriers. Major current problems involve the extraction of these molecules; how to do it, what to do when it is achieved, and how (and if) it is relevant to the central problems of membrane function. Further advances are expected soon from studies of rate barriers within membranes, of voltage-dependent (\"excitable\") conducting channels, and of increasingly complex model systems and biological membranes."}
{"id": "PMID:453", "title": "Photoreceptor processes: some problems and perspectives.", "content": "Visual photoreceptors from both vertebrates and invertebrates are characterized by extensive elaboration of membrane which contains visual pigment (rhodopsin). Visual pigments in all phyla examined are chemically similar: the chromophore is 11-cis retinaldehyde attached by an aldimine linkage (Schiff base) to a membrane protein, opsin. The effect of light is to isomerize the chromophore to the all-trans configuration. Beyond these fundamental similarities, several specific areas are discussed in which variations and differences appear. (1) Light causes vertebrate visual pigments to bleach, liberating the chromophore. Most invertebrate visual pigments do not bleach in the light, but instead form a thermally stable metarhodopsin, with the chromophore in the all-trans configuration still attached to the opsin. (2) In the disk membranes of vertebrate rod and cone outer segments, the rhodopsin molecules are oriented with their chromophores nearly coplanar with the disks. Within this plane, however, both rotational and translational diffusion are possible. In the microvillar membranes of arthropod and cephalopod rhabdoms, on the other hand, the situation is less clear. There is evidence for some preferential orientation of chromophores that implies restrictions on Brownian rotation. (3) In the outer segments of vertebrate receptors, absorption of light by rhodopsin causes the plasma membrane to hyperpolarize due to a decrease in sodium conductance, possibly mediated by calcium ions. In most invertebrate photoreceptors, light causes a depolarization due to an increase in conductance, principally to sodium ions. A subsequent entry of calcium causes a partial repolarization of the membrane, due to a decrease in sodium conductance. (4) For vertebrate receptors, log threshold is directly proportional to the fraction of rhodopsin bleached (Dowling-Rushton relationship). The proportionality constant varies in different preparations from less than four to more than 30, and the physical basis for the relationship is unknown. For invertebrates, by contrast, the dependence of sensitivity on rhodopsin concentration is much less dramatic and may well depend simply on the probability of quantum catch. (5) In most species, vertebrate and invertebrate, the accumulation of photoproduct probably has no effect on membrane conductance, but several possible exceptions exist. (6) Photoregeneration of rhodopsin from metarhodopsin is likely an important mechanism of recovery in certain arthropods such as diurnal insects, but dark mechanisms of recovery also exist in all phyla. In no single case are they adequately understood.", "contents": "Photoreceptor processes: some problems and perspectives. Visual photoreceptors from both vertebrates and invertebrates are characterized by extensive elaboration of membrane which contains visual pigment (rhodopsin). Visual pigments in all phyla examined are chemically similar: the chromophore is 11-cis retinaldehyde attached by an aldimine linkage (Schiff base) to a membrane protein, opsin. The effect of light is to isomerize the chromophore to the all-trans configuration. Beyond these fundamental similarities, several specific areas are discussed in which variations and differences appear. (1) Light causes vertebrate visual pigments to bleach, liberating the chromophore. Most invertebrate visual pigments do not bleach in the light, but instead form a thermally stable metarhodopsin, with the chromophore in the all-trans configuration still attached to the opsin. (2) In the disk membranes of vertebrate rod and cone outer segments, the rhodopsin molecules are oriented with their chromophores nearly coplanar with the disks. Within this plane, however, both rotational and translational diffusion are possible. In the microvillar membranes of arthropod and cephalopod rhabdoms, on the other hand, the situation is less clear. There is evidence for some preferential orientation of chromophores that implies restrictions on Brownian rotation. (3) In the outer segments of vertebrate receptors, absorption of light by rhodopsin causes the plasma membrane to hyperpolarize due to a decrease in sodium conductance, possibly mediated by calcium ions. In most invertebrate photoreceptors, light causes a depolarization due to an increase in conductance, principally to sodium ions. A subsequent entry of calcium causes a partial repolarization of the membrane, due to a decrease in sodium conductance. (4) For vertebrate receptors, log threshold is directly proportional to the fraction of rhodopsin bleached (Dowling-Rushton relationship). The proportionality constant varies in different preparations from less than four to more than 30, and the physical basis for the relationship is unknown. For invertebrates, by contrast, the dependence of sensitivity on rhodopsin concentration is much less dramatic and may well depend simply on the probability of quantum catch. (5) In most species, vertebrate and invertebrate, the accumulation of photoproduct probably has no effect on membrane conductance, but several possible exceptions exist. (6) Photoregeneration of rhodopsin from metarhodopsin is likely an important mechanism of recovery in certain arthropods such as diurnal insects, but dark mechanisms of recovery also exist in all phyla. In no single case are they adequately understood."}
{"id": "PMID:454", "title": "Hydrolysis of the hen egg vitelline membrane by cock sperm acrosin and other enzymes.", "content": "A technique utilizing Pregnant Mare's Serum Gonadotropin and Human Chorionic Gonadotropin treatment of hens (Gallus domesticus), followed by manual ovulation of the excised follicles, was developed to obtain a large number of mature ova. The intact ova were used to test whether acrosin, partially purified from the spermatozoa of the cock (Gallus domesticus), partially purified rabbit testicular acrosin and commercial preparations of several hydrolytic enzymes could dissolve the inner vitelline membrane. Enzymes were applied to pieces of filter paper placed on the ovum. Cock acrosin and endopeptidases such as trypsin, chymotrypsin, collagenase and elastase hydrolyzed the membrane whereas exopeptidases such as leucine aminopeptidase and carboxypeptidase A did not. Phospholipase A, sulfatase, hyaluronidase, beta-glucuronidase and rabbit testicular acrosin also failed to hydrolyze the membrane. Cock acrosin hydrolysis of the ovum surface was inhibited by soybean trypsin inhibitor. The surface of the ovum over the germinal disc region was hydrolyzed more quickly by cock acrosin than the surface over other regions of the ovum. Acrosin from cock sperm caused the release of trichloroacetic acid soluble material absorbing at 280 nm from sonicated preparations of inner vitelline membranes. Hydrolysis was greatest at pH 8.0 and was inhibited by soybean trypsin inhibitor.", "contents": "Hydrolysis of the hen egg vitelline membrane by cock sperm acrosin and other enzymes. A technique utilizing Pregnant Mare's Serum Gonadotropin and Human Chorionic Gonadotropin treatment of hens (Gallus domesticus), followed by manual ovulation of the excised follicles, was developed to obtain a large number of mature ova. The intact ova were used to test whether acrosin, partially purified from the spermatozoa of the cock (Gallus domesticus), partially purified rabbit testicular acrosin and commercial preparations of several hydrolytic enzymes could dissolve the inner vitelline membrane. Enzymes were applied to pieces of filter paper placed on the ovum. Cock acrosin and endopeptidases such as trypsin, chymotrypsin, collagenase and elastase hydrolyzed the membrane whereas exopeptidases such as leucine aminopeptidase and carboxypeptidase A did not. Phospholipase A, sulfatase, hyaluronidase, beta-glucuronidase and rabbit testicular acrosin also failed to hydrolyze the membrane. Cock acrosin hydrolysis of the ovum surface was inhibited by soybean trypsin inhibitor. The surface of the ovum over the germinal disc region was hydrolyzed more quickly by cock acrosin than the surface over other regions of the ovum. Acrosin from cock sperm caused the release of trichloroacetic acid soluble material absorbing at 280 nm from sonicated preparations of inner vitelline membranes. Hydrolysis was greatest at pH 8.0 and was inhibited by soybean trypsin inhibitor."}
{"id": "PMID:459", "title": "Some effects of low pH on chloride exchange in human red blood cells.", "content": "In order to test the range of pH values over which the titratable carried model for inorganic anion exchange is valid, chloride self-exchange across human red blood cells was examined between pH 4.75 and 5.7 at 0 decrees c. It was found that chloride self-exchange flux had a minimum near pH 5 and increased again with further increase in hydrogen ion activity. The Arrhenius activation energy for chloride exchange was greatly reduced at low pH values. The chloride flux at pH 5.1 did not show the saturation kinetics reported at higher pH values but was proportional to the value of the chloride concentration squared. In addition, the extent of inhibition of chloride self-exchange flux by phloretin was reduced at low pH. Our interpretation of these findings is that the carrier-mediated flux becomes a progressively smaller fraction of the total flux at lower pH values and that a different transport mode requiring two chloride ions to form the permeant species and having a low specificity and temperature dependence becomes significant below pH5. A possible mechanism for this transport is that chloride crosses red cell membranes as dimers of HCl at these very low pH values.", "contents": "Some effects of low pH on chloride exchange in human red blood cells. In order to test the range of pH values over which the titratable carried model for inorganic anion exchange is valid, chloride self-exchange across human red blood cells was examined between pH 4.75 and 5.7 at 0 decrees c. It was found that chloride self-exchange flux had a minimum near pH 5 and increased again with further increase in hydrogen ion activity. The Arrhenius activation energy for chloride exchange was greatly reduced at low pH values. The chloride flux at pH 5.1 did not show the saturation kinetics reported at higher pH values but was proportional to the value of the chloride concentration squared. In addition, the extent of inhibition of chloride self-exchange flux by phloretin was reduced at low pH. Our interpretation of these findings is that the carrier-mediated flux becomes a progressively smaller fraction of the total flux at lower pH values and that a different transport mode requiring two chloride ions to form the permeant species and having a low specificity and temperature dependence becomes significant below pH5. A possible mechanism for this transport is that chloride crosses red cell membranes as dimers of HCl at these very low pH values."}
{"id": "PMID:460", "title": "Ionic properties of the acetylcholine receptor in cultured rat myotubes.", "content": "The acetylcholine reversal potential (Er) of cultured rat myotubes is -3mV. When activated, the receptor is permeable to K+ and Na+, but not to Cl- ions. Measurement of Er in Tris+-substituted, Na-free medium also indicated a permeability to Tris+ ions. Unlike adult frog muscle the magnitude of Er was insensitive to change in external Ca++ (up to 30 mM) or to changes in external pH (between 6.4 and 8.9). The equivalent circuit equation describing the electrical circuit composed of two parallel ionic batteries (EK and ENa) and their respective conductances (gK and gNa), which has been generally useful in describing the Er of adult rat and frog muscle, could also be applied to rat myotubes when Er was measured over a wide range of external Na+ concentrations. The equivalent circuit equation could not be applied to myotubes bathed in media of different external K+ concentrations. In this case, the Er was more closely described by the Goldman constant field equation. Under certain circumstances, it is known that the receptor in adult rat and frog muscle can be induced to reversibly shift from behavior described by the equivalent circuit equation to that described by the Goldman equation. Attempts to similarly manipulate the responses of cultured rat myotubes were unsussessful. These trials included a reduction in temperature (15 degress C), partial alpha-bungarotoxin blodkade, and activation of responses with the cholinergic agonist, decamethonium.", "contents": "Ionic properties of the acetylcholine receptor in cultured rat myotubes. The acetylcholine reversal potential (Er) of cultured rat myotubes is -3mV. When activated, the receptor is permeable to K+ and Na+, but not to Cl- ions. Measurement of Er in Tris+-substituted, Na-free medium also indicated a permeability to Tris+ ions. Unlike adult frog muscle the magnitude of Er was insensitive to change in external Ca++ (up to 30 mM) or to changes in external pH (between 6.4 and 8.9). The equivalent circuit equation describing the electrical circuit composed of two parallel ionic batteries (EK and ENa) and their respective conductances (gK and gNa), which has been generally useful in describing the Er of adult rat and frog muscle, could also be applied to rat myotubes when Er was measured over a wide range of external Na+ concentrations. The equivalent circuit equation could not be applied to myotubes bathed in media of different external K+ concentrations. In this case, the Er was more closely described by the Goldman constant field equation. Under certain circumstances, it is known that the receptor in adult rat and frog muscle can be induced to reversibly shift from behavior described by the equivalent circuit equation to that described by the Goldman equation. Attempts to similarly manipulate the responses of cultured rat myotubes were unsussessful. These trials included a reduction in temperature (15 degress C), partial alpha-bungarotoxin blodkade, and activation of responses with the cholinergic agonist, decamethonium."}
{"id": "PMID:461", "title": "Effect of cross-reinnervation on physiological parameters and on properties of myosin and sarcoplasmic reticulum of fast and slow muscles of the rabbit.", "content": "Cross-reinnvervation of fast (extensor digitorum longus) and slow (soleus) twitch muscles of the rabbit showed essentially complete fast to slow and slow to fast conversion, respectively, 11-12 mo after surgery with respect to a number of physiological parameters including intrinsic shortening, velocity, and isometric twitch time to peak. There was pronounced bu incomplete biochemical conversion as judged by Ca2+ uptake by sarcoplasmic reticulum, myosin ATPase, alkali lability, and light chain complement. The question of trophic substances of neural origin is discussed in light of the fact that chronic stimulation for 15 wk of a fast muscle produces complete biochemical and physiological conversion to the slow type.", "contents": "Effect of cross-reinnervation on physiological parameters and on properties of myosin and sarcoplasmic reticulum of fast and slow muscles of the rabbit. Cross-reinnvervation of fast (extensor digitorum longus) and slow (soleus) twitch muscles of the rabbit showed essentially complete fast to slow and slow to fast conversion, respectively, 11-12 mo after surgery with respect to a number of physiological parameters including intrinsic shortening, velocity, and isometric twitch time to peak. There was pronounced bu incomplete biochemical conversion as judged by Ca2+ uptake by sarcoplasmic reticulum, myosin ATPase, alkali lability, and light chain complement. The question of trophic substances of neural origin is discussed in light of the fact that chronic stimulation for 15 wk of a fast muscle produces complete biochemical and physiological conversion to the slow type."}
{"id": "PMID:462", "title": "Chitin synthase in Mortierella vinacea: properties, cellular location and synthesis in growing cultures.", "content": "Chitin synthase of Mortierella vinacea was present in the \"microsomal' fraction (100 000 g precipitate), the 'cell-wall' fraction (2000 g precipitate) and the 'mitochondrial' fraction (10 000 g precipitate). The properties of the 'microsomal' enzyme were investigated. The pH optimum was between 5-8 and 6-2, and the temperature optimum was between 31 and 33 degrees C. The Km for UDP N-acetyl-D-glucosamine was 1.8 mM. The enzyme was stimulated by Mg2+ and a slight stimulation was also effected by N-acetyl-D-glucosamine. Soluble chitodextrins were inhibitory. A pH-dependent, heat-stable inhibitor of chitin synthase activity was present in the soluble cytoplasm from the mycelium. The effects of aeration and glucose concentration on enzyme production in growing cultures were also investigated; maximum specific activity of chitin synthase was associated with the cessation of exponential growth.", "contents": "Chitin synthase in Mortierella vinacea: properties, cellular location and synthesis in growing cultures. Chitin synthase of Mortierella vinacea was present in the \"microsomal' fraction (100 000 g precipitate), the 'cell-wall' fraction (2000 g precipitate) and the 'mitochondrial' fraction (10 000 g precipitate). The properties of the 'microsomal' enzyme were investigated. The pH optimum was between 5-8 and 6-2, and the temperature optimum was between 31 and 33 degrees C. The Km for UDP N-acetyl-D-glucosamine was 1.8 mM. The enzyme was stimulated by Mg2+ and a slight stimulation was also effected by N-acetyl-D-glucosamine. Soluble chitodextrins were inhibitory. A pH-dependent, heat-stable inhibitor of chitin synthase activity was present in the soluble cytoplasm from the mycelium. The effects of aeration and glucose concentration on enzyme production in growing cultures were also investigated; maximum specific activity of chitin synthase was associated with the cessation of exponential growth."}
{"id": "PMID:463", "title": "Protoplasts of Schizosaccharomyces pombe: an improved method for their preparation and the study of their guanine uptake.", "content": "A new method is described for the efficient conversion of Schizosaccharomyces pombe cells into protoplasts. The following parameters of guanine uptake determined in whole cells were unchanged in protoplasts: Km value, requirement for an energy source, sensitivity to competitive inhibitors, pH optimum, as well as the typical variation of the initial velocity of uptake observed during the growth phase.", "contents": "Protoplasts of Schizosaccharomyces pombe: an improved method for their preparation and the study of their guanine uptake. A new method is described for the efficient conversion of Schizosaccharomyces pombe cells into protoplasts. The following parameters of guanine uptake determined in whole cells were unchanged in protoplasts: Km value, requirement for an energy source, sensitivity to competitive inhibitors, pH optimum, as well as the typical variation of the initial velocity of uptake observed during the growth phase."}
{"id": "PMID:464", "title": "Manganese mutagenesis in yeast. A practical application of manganese for the induction of mitochondrial antibiotic-resistant mutations.", "content": "When yeast cells were incubated for 4 to 8 h in yeast extract-peptone-glucose medium, pH 6, containing 8 mM-manganese, and then plated on selective media, there was a strong induction of antibiotic-resistant mutations. Indirect evidence suggests that practically all resistant mutants selected were of independent origin. The analysis of manganese-induced resistant mutants showed that most were extranuclear, while those tested showed recombination with known mitochondrial markers. Our results suggest that manganese can be considered as a mutagen which specifically induces mitochondrial mutations in Saccharomyces cerevisiae.", "contents": "Manganese mutagenesis in yeast. A practical application of manganese for the induction of mitochondrial antibiotic-resistant mutations. When yeast cells were incubated for 4 to 8 h in yeast extract-peptone-glucose medium, pH 6, containing 8 mM-manganese, and then plated on selective media, there was a strong induction of antibiotic-resistant mutations. Indirect evidence suggests that practically all resistant mutants selected were of independent origin. The analysis of manganese-induced resistant mutants showed that most were extranuclear, while those tested showed recombination with known mitochondrial markers. Our results suggest that manganese can be considered as a mutagen which specifically induces mitochondrial mutations in Saccharomyces cerevisiae."}
{"id": "PMID:465", "title": "The properties and large-scale production of L-asparaginase from citrobacter.", "content": "An intracellular L-asparaginase with antitumour activity was purified from a strain of Citrobacter. The optimum conditions for enzyme production by fermentation on scales up to 2700 l were investigated. Highest enzyme yield was obtained in corn-steep liquor medium (9-2%, W/V) at 37 degrees C. Oxygen limitation was not necessary for high enzyme yield. A total recovery of 4-3% from nucleic-acid-free extract and a 180-fold increase in specific activity were obtained after purificaiton. The specific activity of the purified preparation was 45 i.u./mg protein. The enzyme hydrolysed D-asparagine and L-glutamine at 7 and 5%, respectively, of its activity toward L-asparagine, but L-glutaminase activity could be demonstrated only at substrate concentrations above 5 mM. The Km values for L-asparagine and D-asparagine were 2-6 X 10(-5) and 1-4 X 10(-4) respectively. The anti-lymphoma activity of the enzyme was demonstrated with Gardner lymphosarcoma and was found only slightly less potent that Crasnitin, the most active asparaginase so far tested in this system.", "contents": "The properties and large-scale production of L-asparaginase from citrobacter. An intracellular L-asparaginase with antitumour activity was purified from a strain of Citrobacter. The optimum conditions for enzyme production by fermentation on scales up to 2700 l were investigated. Highest enzyme yield was obtained in corn-steep liquor medium (9-2%, W/V) at 37 degrees C. Oxygen limitation was not necessary for high enzyme yield. A total recovery of 4-3% from nucleic-acid-free extract and a 180-fold increase in specific activity were obtained after purificaiton. The specific activity of the purified preparation was 45 i.u./mg protein. The enzyme hydrolysed D-asparagine and L-glutamine at 7 and 5%, respectively, of its activity toward L-asparagine, but L-glutaminase activity could be demonstrated only at substrate concentrations above 5 mM. The Km values for L-asparagine and D-asparagine were 2-6 X 10(-5) and 1-4 X 10(-4) respectively. The anti-lymphoma activity of the enzyme was demonstrated with Gardner lymphosarcoma and was found only slightly less potent that Crasnitin, the most active asparaginase so far tested in this system."}
{"id": "PMID:466", "title": "Effect of inorganic phosphate on acridine inhibition and plasmid curing in Escherichia coli.", "content": "Some mutants and stock strains of Escherichia coli K12 were sensitive to acriflavine in the presence of inorganic phosphate but were resistant to acriflavine in its absence. They mutated spontaneously to resistance to acriflavine plus phosphate. The synergistic effect of phosphate on acriflavine sensitivity was increased at high pH values. Genetic analysis suggested that the mutations occurred in the gene acrA. Electron microscopic observation suggested that the presence of acriflavine plus phosphate affected the structure of the plasma membrane and the cytoplasm under it. This structural alteration was not caused by acriflavine alone. Acridine orange plus phosphate can more effectively eliminate the plasmid F8-gal+ than acridine orange alone.", "contents": "Effect of inorganic phosphate on acridine inhibition and plasmid curing in Escherichia coli. Some mutants and stock strains of Escherichia coli K12 were sensitive to acriflavine in the presence of inorganic phosphate but were resistant to acriflavine in its absence. They mutated spontaneously to resistance to acriflavine plus phosphate. The synergistic effect of phosphate on acriflavine sensitivity was increased at high pH values. Genetic analysis suggested that the mutations occurred in the gene acrA. Electron microscopic observation suggested that the presence of acriflavine plus phosphate affected the structure of the plasma membrane and the cytoplasm under it. This structural alteration was not caused by acriflavine alone. Acridine orange plus phosphate can more effectively eliminate the plasmid F8-gal+ than acridine orange alone."}
{"id": "PMID:467", "title": "Oxidation of carbon monoxide and methane by Pseudomonas methanica.", "content": "The oxidation of carbon monoxide and methane by suspensions and ultrasonic extracts of Pseudomonas methanica was studied. A continuous assay for the oxidation of CO to CO2 was devised, using O2 and CO2 electrodes in combination. Stoicheiometries of CO-dependent CO2 formation, O2 consumption and NADH oxidation, and the partial stoicheiometries of methane-dependent NADH oxidation, suggest the involvement of a mono-oxygenase in these oxidations. Evidence is presented suggesting methane and CO oxidation are catalysed by a single enzyme system, distinct, at least in part, from the NADH oxidase present in extracts. Ethanol was able to provide the reductant necessary for CO oxidation by cell suspensions, though the metabolism of ethanol by P. methanica was found unlikely to result in substrate-level formation of NADH; the means whereby alcohol oxidation could supply reductant for the mono-oxygenase are discussed.", "contents": "Oxidation of carbon monoxide and methane by Pseudomonas methanica. The oxidation of carbon monoxide and methane by suspensions and ultrasonic extracts of Pseudomonas methanica was studied. A continuous assay for the oxidation of CO to CO2 was devised, using O2 and CO2 electrodes in combination. Stoicheiometries of CO-dependent CO2 formation, O2 consumption and NADH oxidation, and the partial stoicheiometries of methane-dependent NADH oxidation, suggest the involvement of a mono-oxygenase in these oxidations. Evidence is presented suggesting methane and CO oxidation are catalysed by a single enzyme system, distinct, at least in part, from the NADH oxidase present in extracts. Ethanol was able to provide the reductant necessary for CO oxidation by cell suspensions, though the metabolism of ethanol by P. methanica was found unlikely to result in substrate-level formation of NADH; the means whereby alcohol oxidation could supply reductant for the mono-oxygenase are discussed."}
{"id": "PMID:468", "title": "Systematic desensitization to reduce dream-induced anxiety.", "content": "A modified version of systematic desensitization was used to reduce the anxiety and negative interpersonal consequences produced by a recurrent aversive dream resulting from events in the real world. The subject, a 16-year-old incarcerated male, was first taught a standard relaxation technique. The subject's dream was divided into 12 hierarchical imaginal scenes. Following initial relaxation, each scene was sequentially introduced and followed by the therapist's suggestion that the subject was still very relaxed. After three sessions with the therapists and several practice sessions by himself, the subject reported no further anxiety to the dream (which continued to occur) and improved relations with the institutional staff. Six months of follow-up showed no recurrence of the anxiety or the subsequent irritability which the subject had initially reported as leading to negative interpersonal relations with the staff.", "contents": "Systematic desensitization to reduce dream-induced anxiety. A modified version of systematic desensitization was used to reduce the anxiety and negative interpersonal consequences produced by a recurrent aversive dream resulting from events in the real world. The subject, a 16-year-old incarcerated male, was first taught a standard relaxation technique. The subject's dream was divided into 12 hierarchical imaginal scenes. Following initial relaxation, each scene was sequentially introduced and followed by the therapist's suggestion that the subject was still very relaxed. After three sessions with the therapists and several practice sessions by himself, the subject reported no further anxiety to the dream (which continued to occur) and improved relations with the institutional staff. Six months of follow-up showed no recurrence of the anxiety or the subsequent irritability which the subject had initially reported as leading to negative interpersonal relations with the staff."}
{"id": "PMID:472", "title": "Experimental evaluation of the spasmogenicity of dopamine on the basilar artery.", "content": "Arteriograms of the basilar artery reveal that dopamine given intracisternally to dogs can generate cerebral vasospasm. This finding supports a recent hypothesis of others that dopamine may play a role in the pathogenesis of vasospasm, especially since many substances are known which fail to produce such spasm. Compared to blood or prostaglandin E2, however, the spasm induced by dopamine was delayed in onset, less in incidence, and usually less intense. Possible explanations for such experimental differences are discussed.", "contents": "Experimental evaluation of the spasmogenicity of dopamine on the basilar artery. Arteriograms of the basilar artery reveal that dopamine given intracisternally to dogs can generate cerebral vasospasm. This finding supports a recent hypothesis of others that dopamine may play a role in the pathogenesis of vasospasm, especially since many substances are known which fail to produce such spasm. Compared to blood or prostaglandin E2, however, the spasm induced by dopamine was delayed in onset, less in incidence, and usually less intense. Possible explanations for such experimental differences are discussed."}
{"id": "PMID:475", "title": "Fatty acid and ketone body metabolism in the rat: response to diet and exercise.", "content": "This study was designed to measure the response of key enzymes of ketone body metabolism in heart, skeletal muscle, and liver to diet and exercise, two conditions known to influence ketone body utilization. A 3 (diet: control, high fat, or high carbohydrate) X 2 (kill condition: rested or exhausted) X 2 (training: trained or untrained) factorial design was used to estimate main experimental effects as well as identify significant interactions of the variables. Physical training (treadmill running) was associated with a doubling of the activity of skeletal muscle 3-oxoacid CoA transferase, a key enzyme in extrahepatic ketone body utilization. The activity of the rate-limiting enzyme of liver ketone body production, hydroxymethylglutaryl CoA synthetase (HMG CoA synthetase), was not greatly influenced by training or exhuastive exercise indicating that the metabolic control of the ketosis of exercise may more likely be a function of the supply of fatty acids to the liver rather than the activity of HMG CoA synthetase. Feeding a high fat diet, on the other hand, significantly increased the activity of liver HMG CoA synthetase, indicating that the ketosis of fat feeding may be of a different nature than that of exercise. The results of this study indicate that physical training is associated with biochemical adaptations in ketone body metabolism as well as fatty acid oxidation, and that trained individuals are metabolically better endowed to benefit from the ketosis of exercise than untrained individuals.", "contents": "Fatty acid and ketone body metabolism in the rat: response to diet and exercise. This study was designed to measure the response of key enzymes of ketone body metabolism in heart, skeletal muscle, and liver to diet and exercise, two conditions known to influence ketone body utilization. A 3 (diet: control, high fat, or high carbohydrate) X 2 (kill condition: rested or exhausted) X 2 (training: trained or untrained) factorial design was used to estimate main experimental effects as well as identify significant interactions of the variables. Physical training (treadmill running) was associated with a doubling of the activity of skeletal muscle 3-oxoacid CoA transferase, a key enzyme in extrahepatic ketone body utilization. The activity of the rate-limiting enzyme of liver ketone body production, hydroxymethylglutaryl CoA synthetase (HMG CoA synthetase), was not greatly influenced by training or exhuastive exercise indicating that the metabolic control of the ketosis of exercise may more likely be a function of the supply of fatty acids to the liver rather than the activity of HMG CoA synthetase. Feeding a high fat diet, on the other hand, significantly increased the activity of liver HMG CoA synthetase, indicating that the ketosis of fat feeding may be of a different nature than that of exercise. The results of this study indicate that physical training is associated with biochemical adaptations in ketone body metabolism as well as fatty acid oxidation, and that trained individuals are metabolically better endowed to benefit from the ketosis of exercise than untrained individuals."}
{"id": "PMID:476", "title": "Some mechanisms of reduction of carotenoid levels in chickens infected with Eimeria acervulina or E. tenella.", "content": "The levels of plasma carotenoids were markedly reduced in broiler cockerels infected with Eimeria acervulina or E. tenella. The mechanisms of this depigmentation differed between the two species, being primarily associated with interference of absorption of xanthophyll (carotenoids) from the intestinal lumen with E. acervulina infection and with leakage through the damaged wall of the cecum with E. tenella infection. Chicks reared on an essentially carotenoid-free diet and inoculated with E. acervulina showed no detectable levels of carotenoids in the blood 48 hours after being changed to a diet containing 30 mg of xanthophyll/kg. Conversely, uninoculated chicks and chicks inoculated with E. tenella showed significant and similar increases in plasma levels of carotenoids. Chicks reared on a diet containing xanthophyll and inoculated with E. tenella showed a more rapid decrease in plasma carotenoids than did uninoculated controls when changed to a xanthophyll-free diet. In chicks fed high xanthophyll diets containing chromic oxide, no indication of malabsorption was seen in chicks infected with E. tenella compared with uninoculated controls, whereas chicks inoculated with E. acervulina showed significantly less xanthophyll absorption. Conversely, a marked increase in the xanthophyll : Cr2O3 ratio was observed in the cecal contents of chicks inoculated with E. tenella compared with uninuoculated controls or those inoculated with E. acervulina. Studies of uninoculated chicks pair-fed with chicks inoculated with E. acervulina or E. tenella indicated that the decrease in plasma carotenoids and increases in intestinal pH are not associated with the reduced intake of feed associated with infection. The studies involving uninoculated birds with reciprocal chagnes between high and low xanthophyll diets indicated that plasma carotenoids are a more rapid and sensitive means of measuring changes in pigmentation levels than are visual skin scores carotenoid levels from the skin.", "contents": "Some mechanisms of reduction of carotenoid levels in chickens infected with Eimeria acervulina or E. tenella. The levels of plasma carotenoids were markedly reduced in broiler cockerels infected with Eimeria acervulina or E. tenella. The mechanisms of this depigmentation differed between the two species, being primarily associated with interference of absorption of xanthophyll (carotenoids) from the intestinal lumen with E. acervulina infection and with leakage through the damaged wall of the cecum with E. tenella infection. Chicks reared on an essentially carotenoid-free diet and inoculated with E. acervulina showed no detectable levels of carotenoids in the blood 48 hours after being changed to a diet containing 30 mg of xanthophyll/kg. Conversely, uninoculated chicks and chicks inoculated with E. tenella showed significant and similar increases in plasma levels of carotenoids. Chicks reared on a diet containing xanthophyll and inoculated with E. tenella showed a more rapid decrease in plasma carotenoids than did uninoculated controls when changed to a xanthophyll-free diet. In chicks fed high xanthophyll diets containing chromic oxide, no indication of malabsorption was seen in chicks infected with E. tenella compared with uninoculated controls, whereas chicks inoculated with E. acervulina showed significantly less xanthophyll absorption. Conversely, a marked increase in the xanthophyll : Cr2O3 ratio was observed in the cecal contents of chicks inoculated with E. tenella compared with uninuoculated controls or those inoculated with E. acervulina. Studies of uninoculated chicks pair-fed with chicks inoculated with E. acervulina or E. tenella indicated that the decrease in plasma carotenoids and increases in intestinal pH are not associated with the reduced intake of feed associated with infection. The studies involving uninoculated birds with reciprocal chagnes between high and low xanthophyll diets indicated that plasma carotenoids are a more rapid and sensitive means of measuring changes in pigmentation levels than are visual skin scores carotenoid levels from the skin."}
{"id": "PMID:477", "title": "Metabolic studies on the development of ethanol-induced fatty liver in KK-Ay mice.", "content": "Mechanisms involved in the development of the alcoholic fatty liver in KK-Ay mice were investigated. Incorporation studies using [14C]acetate and [3H]palmitate indicated that the half-life of hepatic triglycerides was doubled in the ethanol-ingesting mice, and utilization of the exogenous fat was significantly increases as compared with that of the control. No persistent alteration was recognized in hepatic oxidation of palmitate, as estimated by in vitro experiments using liver slices obtained from control and ethanol-drinking mice. Enzymic studies indicated that the activities of acetyl COA carboxylase, ATP citrate lyase, malic enzyme, and 6-phosphogluconate dehydrogenase were increased with ethanol drinking. The increment in hepatic triglycerides accumulated during ethanol ingestion was largely accounted for by palmitoleic, oleic, and linoleic acids. These findings demonstrated an augmentation in hepatic lipogenesis as well as an increased utilization of exogenous fats. Ethanol drinking did not cause any appreciable change in plasma triglyceride level and metabolism of adipose tissue. In summary of the present studies, accelerated lipogenesis and increased utilization of the dietary fats may be possible causal factors in the alcoholic fatty liver of KK-Ay mice.", "contents": "Metabolic studies on the development of ethanol-induced fatty liver in KK-Ay mice. Mechanisms involved in the development of the alcoholic fatty liver in KK-Ay mice were investigated. Incorporation studies using [14C]acetate and [3H]palmitate indicated that the half-life of hepatic triglycerides was doubled in the ethanol-ingesting mice, and utilization of the exogenous fat was significantly increases as compared with that of the control. No persistent alteration was recognized in hepatic oxidation of palmitate, as estimated by in vitro experiments using liver slices obtained from control and ethanol-drinking mice. Enzymic studies indicated that the activities of acetyl COA carboxylase, ATP citrate lyase, malic enzyme, and 6-phosphogluconate dehydrogenase were increased with ethanol drinking. The increment in hepatic triglycerides accumulated during ethanol ingestion was largely accounted for by palmitoleic, oleic, and linoleic acids. These findings demonstrated an augmentation in hepatic lipogenesis as well as an increased utilization of exogenous fats. Ethanol drinking did not cause any appreciable change in plasma triglyceride level and metabolism of adipose tissue. In summary of the present studies, accelerated lipogenesis and increased utilization of the dietary fats may be possible causal factors in the alcoholic fatty liver of KK-Ay mice."}
{"id": "PMID:479", "title": "Renal response to acid loading in the developing lamb fetus, intact in utero.", "content": "Response of the fetal kidney to metabolic acidosis was studied in five fetal lambs, 115-125 days gestation, in order to evaluate the renal contribution to elimination of hydrogen ion during intra-uterine development. Experiments were conducted on healthy unanesthetized fetuses, intact in utero, with catheters implanted at hysterotomy into a fetal femoral artery and vein and into the bladder via the urachus, four or more days prior to the study. A metabolic acidosis was induced by infusion of isotonic lactic acid, 15 m mole/kg, intravenously over a period of 90 minutes. Serial arterial samples were taken and urine collected in fractions before, during and for three hours following the infusion, for measurements of pH, bicarbonate, lactate and electrolytes as well as urine output. During the infusion, urine pH fell from 6.65 to 6.25 and was 6.34 three hours later (Figs. 1 to 4, Tabs. III to IV). Lactic acid infusion caused a prompt increase in urine output from a mean rate of 0.12 to a maximum of 0.28 ml/kg/min at the end of the infusion, returning to control rates three hours later. Lactate excretion increased from 0.05 to a maximum of 4.6 mumole/kg/min at the end of infusion; titratable acid increased from 0.22 to a maximum of 4 muEq/kg/min; the rates of excretion of lactate and titratable acid were still higher than control at the end of three hours. Ammonia excretion increased from 0.21 to a maximum of 0.56 muEq/kg/min three hours after the end of infusion. The acid infusion caused a small but significant fall in excretion of bicarbonate. During the 90 minutes of infusion and over the following three hours, about 800 mumole lactate was excreted while net acid excretion over the same period was no more than half that amount. The diuresis was also accompanied by a net loss of sodium and chloride, the excretion of these ions increasing more than threefold following acid infusion; excretion of potassium decreased to one-third its rate prior to the infusion. During the 90 minutes of infusion, blood pH fell from 7.36 to 7.13, base deficit rose from 3.8 to 16.4 mEq/L and lactate rose from 2.2 to 14.8 mM/L; there was also a small but significant rise in both blood PCO2 and PO2 (Figs. 1 to 2, Tabs. I to II). During the following three hours of recovery, pH rose gradually to 7.29, base deficit and lactate fell to 7.4 mEq/L and 8.7 mM/L respectively. Since renal excretion of net acid and lactate was small, the decrease in blood base deficit and lactate levels during the recovery must therefore be mainly due to equilibration in various fetal compartments as well as placental transfer. These experiments indicate that, in the lamb fetus, intact in utero, the kidney although limited by immaturity of several mechanisms, is capable of responding to an acid load and thus can make a small contribution to fetal homeostasis. The increase in excretion of net acid is accompanied by loss of sodium and chloride in the urine.", "contents": "Renal response to acid loading in the developing lamb fetus, intact in utero. Response of the fetal kidney to metabolic acidosis was studied in five fetal lambs, 115-125 days gestation, in order to evaluate the renal contribution to elimination of hydrogen ion during intra-uterine development. Experiments were conducted on healthy unanesthetized fetuses, intact in utero, with catheters implanted at hysterotomy into a fetal femoral artery and vein and into the bladder via the urachus, four or more days prior to the study. A metabolic acidosis was induced by infusion of isotonic lactic acid, 15 m mole/kg, intravenously over a period of 90 minutes. Serial arterial samples were taken and urine collected in fractions before, during and for three hours following the infusion, for measurements of pH, bicarbonate, lactate and electrolytes as well as urine output. During the infusion, urine pH fell from 6.65 to 6.25 and was 6.34 three hours later (Figs. 1 to 4, Tabs. III to IV). Lactic acid infusion caused a prompt increase in urine output from a mean rate of 0.12 to a maximum of 0.28 ml/kg/min at the end of the infusion, returning to control rates three hours later. Lactate excretion increased from 0.05 to a maximum of 4.6 mumole/kg/min at the end of infusion; titratable acid increased from 0.22 to a maximum of 4 muEq/kg/min; the rates of excretion of lactate and titratable acid were still higher than control at the end of three hours. Ammonia excretion increased from 0.21 to a maximum of 0.56 muEq/kg/min three hours after the end of infusion. The acid infusion caused a small but significant fall in excretion of bicarbonate. During the 90 minutes of infusion and over the following three hours, about 800 mumole lactate was excreted while net acid excretion over the same period was no more than half that amount. The diuresis was also accompanied by a net loss of sodium and chloride, the excretion of these ions increasing more than threefold following acid infusion; excretion of potassium decreased to one-third its rate prior to the infusion. During the 90 minutes of infusion, blood pH fell from 7.36 to 7.13, base deficit rose from 3.8 to 16.4 mEq/L and lactate rose from 2.2 to 14.8 mM/L; there was also a small but significant rise in both blood PCO2 and PO2 (Figs. 1 to 2, Tabs. I to II). During the following three hours of recovery, pH rose gradually to 7.29, base deficit and lactate fell to 7.4 mEq/L and 8.7 mM/L respectively. Since renal excretion of net acid and lactate was small, the decrease in blood base deficit and lactate levels during the recovery must therefore be mainly due to equilibration in various fetal compartments as well as placental transfer. These experiments indicate that, in the lamb fetus, intact in utero, the kidney although limited by immaturity of several mechanisms, is capable of responding to an acid load and thus can make a small contribution to fetal homeostasis. The increase in excretion of net acid is accompanied by loss of sodium and chloride in the urine."}
{"id": "PMID:480", "title": "Recognition and significance of maternogenic fetal acidosis during intensive monitoring of labor.", "content": "FHR monitoring and microanalysis of fetal blood are mutually complementary procedures, and optimal knowledge of the fetal state is achieved by making use of both, the former for the preliminary screening of all cases at risk and the latter for the purpose of deciding on obstetric management where pathological changes are evident in the FHR. The major difficulty in obtaining a precise value for the fetal acid-base balance lies in the occurence of \"falsely abnormal\" cases, i.e. cases in which the fetal pH falls during labor but the clinical condition at birth is good (APGAR greater than or equal to 7). In our own series the incidence of such cases among fetuses at risk was 11.2% (Tab. I). In the majority of these cases the fetal acidosis is thought to be a result of increased metabolic acidosis in the mother (maternogenic fetal metabolic acidosis). The importance of the maternogenic fetal acidosis during labor lies in the fact that unless it is recognised, rapid extraction of the fetus will appear necessary on clinical grounds, although it is in fact unnecessary, since this form of acidosis has no adverse effect on the fetus. Various parameters have been proposed for the differential diagnosis of the maternogenic fetal acidosis. These include the feto-maternal difference in base deficit (F/M deltaBD), the materno-fetal differences in pHqu 40 (M/F deltapHqu 40) the materno-fetal difference actual pH (M/F actual deltapH), and the materno-fetal difference in base deficit of the extra-cellular fluid (M/F deltaBDHb5). A critical analysis of these parameters has been carried out on the results of microtests performed during a 5 year period (1968-1972) at the First Clinic of Obstetrics and Gynecology of Milan University. The cases comprised 59 regarded as normal (normal course of pregnancy, spontaneous commencement of labor at term, clear amniotic fluid, regular FHR, spontaneous birth, APGAR at 90 sec between 8 and 10, weight at birth greater than 2500 g), and 335 considered to be at risk (maternal disease, presence of meconium stained amniotic fluid and/or abnormal changes in FHR). In all of these cases the FHR was recorded by cardiotokography, and the tracings were interpreted according to HON. Microsamples of blood were taken from both mother and fetus during labor and the following determinations were carried out: actual pH, pHqu 40, Hb concentration, hemoglobin oxygen saturation, base deficit Hb5 (BDHb5). The maternofetal differences were then calculated. The same determinations were carried out on samples of maternal blood and of arterial and venous cord blood taken immediately after delivery. The clinical condition of the infant was evaluated by the APGAR score at 90 seconds after birth.", "contents": "Recognition and significance of maternogenic fetal acidosis during intensive monitoring of labor. FHR monitoring and microanalysis of fetal blood are mutually complementary procedures, and optimal knowledge of the fetal state is achieved by making use of both, the former for the preliminary screening of all cases at risk and the latter for the purpose of deciding on obstetric management where pathological changes are evident in the FHR. The major difficulty in obtaining a precise value for the fetal acid-base balance lies in the occurence of \"falsely abnormal\" cases, i.e. cases in which the fetal pH falls during labor but the clinical condition at birth is good (APGAR greater than or equal to 7). In our own series the incidence of such cases among fetuses at risk was 11.2% (Tab. I). In the majority of these cases the fetal acidosis is thought to be a result of increased metabolic acidosis in the mother (maternogenic fetal metabolic acidosis). The importance of the maternogenic fetal acidosis during labor lies in the fact that unless it is recognised, rapid extraction of the fetus will appear necessary on clinical grounds, although it is in fact unnecessary, since this form of acidosis has no adverse effect on the fetus. Various parameters have been proposed for the differential diagnosis of the maternogenic fetal acidosis. These include the feto-maternal difference in base deficit (F/M deltaBD), the materno-fetal differences in pHqu 40 (M/F deltapHqu 40) the materno-fetal difference actual pH (M/F actual deltapH), and the materno-fetal difference in base deficit of the extra-cellular fluid (M/F deltaBDHb5). A critical analysis of these parameters has been carried out on the results of microtests performed during a 5 year period (1968-1972) at the First Clinic of Obstetrics and Gynecology of Milan University. The cases comprised 59 regarded as normal (normal course of pregnancy, spontaneous commencement of labor at term, clear amniotic fluid, regular FHR, spontaneous birth, APGAR at 90 sec between 8 and 10, weight at birth greater than 2500 g), and 335 considered to be at risk (maternal disease, presence of meconium stained amniotic fluid and/or abnormal changes in FHR). In all of these cases the FHR was recorded by cardiotokography, and the tracings were interpreted according to HON. Microsamples of blood were taken from both mother and fetus during labor and the following determinations were carried out: actual pH, pHqu 40, Hb concentration, hemoglobin oxygen saturation, base deficit Hb5 (BDHb5). The maternofetal differences were then calculated. The same determinations were carried out on samples of maternal blood and of arterial and venous cord blood taken immediately after delivery. The clinical condition of the infant was evaluated by the APGAR score at 90 seconds after birth."}
{"id": "PMID:481", "title": "Solubilization and stabilization of the cytotoxic agent coralyne.", "content": "Kinetic studies were carried out on the ring opening of the quaternary nitrogen cation, coralynium ion (I), to yield 6'-acetylpapaverine (III), on the cyclization of III to yield I, and on a photochemical reaction undergone by I in aqueous solutions exposed to visible light. From the results, it was concluded that: (a) I and III are in facile equilibrium in aqueous solution but appreciable amounts of III do not exist in dilute solutions with pH values below 10: (b) the photochemical reaction of I in water (presumably a photohydration) can be reversed by lyophilization, by heatiing, and by increasing the pH of solutions to values greater than 12; (c) the photochemical reaction of I can be inhibited by protecting the aqueous solutions from visible light, and the rate in the presence of light can be reduced by increasing the concentration of I in the solution; and (d) although the chloride and sulfoacetate salts of I react identically and have similar solubilities in water, it is possible to prepare more concentrated and, hence, more stable solutions of the sulfoacetate salt by including sodium hydroxide in the solvent. The solubility of coralyne chloride remains about the same in dilute sodium hydroxide as in water.", "contents": "Solubilization and stabilization of the cytotoxic agent coralyne. Kinetic studies were carried out on the ring opening of the quaternary nitrogen cation, coralynium ion (I), to yield 6'-acetylpapaverine (III), on the cyclization of III to yield I, and on a photochemical reaction undergone by I in aqueous solutions exposed to visible light. From the results, it was concluded that: (a) I and III are in facile equilibrium in aqueous solution but appreciable amounts of III do not exist in dilute solutions with pH values below 10: (b) the photochemical reaction of I in water (presumably a photohydration) can be reversed by lyophilization, by heatiing, and by increasing the pH of solutions to values greater than 12; (c) the photochemical reaction of I can be inhibited by protecting the aqueous solutions from visible light, and the rate in the presence of light can be reduced by increasing the concentration of I in the solution; and (d) although the chloride and sulfoacetate salts of I react identically and have similar solubilities in water, it is possible to prepare more concentrated and, hence, more stable solutions of the sulfoacetate salt by including sodium hydroxide in the solvent. The solubility of coralyne chloride remains about the same in dilute sodium hydroxide as in water."}
{"id": "PMID:482", "title": "Solvolysis of a substituted imidazoline, mazindol.", "content": "Hydrolysis of mazindol to form 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine was followed spectro-photometrically in aqueous solutions at temperatures between 37 and 70degree, pH values up to 7.6, and an ionic strength of 0.2. The effects of acetate, formate, and phosphate buffers as well as ionic strength on the observed rate constants were investigated. An interesting nonlinear dependency of the kobs with buffer concentration was noted. The velocity constants declined with increasing hydrogen-ion concentration; the log k-pH profile and rate law are given along with other relevant data.", "contents": "Solvolysis of a substituted imidazoline, mazindol. Hydrolysis of mazindol to form 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine was followed spectro-photometrically in aqueous solutions at temperatures between 37 and 70degree, pH values up to 7.6, and an ionic strength of 0.2. The effects of acetate, formate, and phosphate buffers as well as ionic strength on the observed rate constants were investigated. An interesting nonlinear dependency of the kobs with buffer concentration was noted. The velocity constants declined with increasing hydrogen-ion concentration; the log k-pH profile and rate law are given along with other relevant data."}
{"id": "PMID:483", "title": "Complexation in formulation of parenteral solutions: solubilization of the cytotoxic agent hexamethylmelamine by complexation with gentisic acid species.", "content": "The apparent solubility of hexamethylmelamine in aqueous solutions suitable for intravenous use was increased by complexation with gentisic acid. Studies were carried out in the pH 0-8 range. Unprotonated hexamethylmelamine did not form complexes with the gentisate ion, while the hexamethylmelammonium ion appeared to form several different complexes with both the gentidate ion and gentisic acid. Two different solid complexes were isolated and characterized. The solubility increases observed at pH 3.5-5.0 are described by mathematical relationships involving the stability constants of some postulated complex species. From these results, sultable formulations for use as parenteral solutions are proposed. The increase in the apparent aqueous solubility of hexamethylmelamine in such formulations may range from five- to 90-fold, depending upon the pH and total gentisateion concentrations.", "contents": "Complexation in formulation of parenteral solutions: solubilization of the cytotoxic agent hexamethylmelamine by complexation with gentisic acid species. The apparent solubility of hexamethylmelamine in aqueous solutions suitable for intravenous use was increased by complexation with gentisic acid. Studies were carried out in the pH 0-8 range. Unprotonated hexamethylmelamine did not form complexes with the gentisate ion, while the hexamethylmelammonium ion appeared to form several different complexes with both the gentidate ion and gentisic acid. Two different solid complexes were isolated and characterized. The solubility increases observed at pH 3.5-5.0 are described by mathematical relationships involving the stability constants of some postulated complex species. From these results, sultable formulations for use as parenteral solutions are proposed. The increase in the apparent aqueous solubility of hexamethylmelamine in such formulations may range from five- to 90-fold, depending upon the pH and total gentisateion concentrations."}
{"id": "PMID:484", "title": "Inhibitory effect of dioctyl sodium sulfosuccinate on trypsin activity.", "content": "The inhibitory effect of dioctyl sodium sulfosuccinate on the proteolytic activity of trypsin was investigate over the pH 6-8 range. The antitryptic activity was determined using two different substrates: casein and N,alpha-benzoyl-DL-arginine-p-nitroanilide hydrochloride. The mechanistic studies revealed the substrate-inhibitor interaction to be the overall major mechanism of inhibition. This interaction was shown to involve substrate depletion, probably involving some primary sites of the natural substrate casein. Some inhibition was also shown to be due to an interaction between the enzyme and the inhibitior molecules. The interactions of the inhibitor with the enzyme and the substrate were irreversible. The possible therapeutic significance of the inhibitory effect of the surfactant is discussed.", "contents": "Inhibitory effect of dioctyl sodium sulfosuccinate on trypsin activity. The inhibitory effect of dioctyl sodium sulfosuccinate on the proteolytic activity of trypsin was investigate over the pH 6-8 range. The antitryptic activity was determined using two different substrates: casein and N,alpha-benzoyl-DL-arginine-p-nitroanilide hydrochloride. The mechanistic studies revealed the substrate-inhibitor interaction to be the overall major mechanism of inhibition. This interaction was shown to involve substrate depletion, probably involving some primary sites of the natural substrate casein. Some inhibition was also shown to be due to an interaction between the enzyme and the inhibitior molecules. The interactions of the inhibitor with the enzyme and the substrate were irreversible. The possible therapeutic significance of the inhibitory effect of the surfactant is discussed."}
{"id": "PMID:485", "title": "In vitro adsorption of diphenoxylate hydrochloride on activated charcoal and its relationship to pharmacological effects of drug in vivo. I.", "content": "The adsorption of diphenoxylate hydrochloride, a potent antidiarrheal agent, on activated charcoal powder was studied in vitro. Langmuir adsorption isotherms were established at pH 4 and 7, and the maximum adsorption capacity of charcoal for this drug was estimated using these values. Activated charcoal modified the bioavailability of diphenoxylate hydrochloride in vivo. The antipropulsive action of diphenoxylate in the mouse was strongly inhibited in the presence of activated charcoal. A comparative evaluation of charcoal and chromium oxide used as inert, nonabsorbable markers revealed that chromium oxide may be the marker of choic in GI transit studies in laboratory animals since it does not influence the bioavailability of diphenoxylate hydrochloride.", "contents": "In vitro adsorption of diphenoxylate hydrochloride on activated charcoal and its relationship to pharmacological effects of drug in vivo. I. The adsorption of diphenoxylate hydrochloride, a potent antidiarrheal agent, on activated charcoal powder was studied in vitro. Langmuir adsorption isotherms were established at pH 4 and 7, and the maximum adsorption capacity of charcoal for this drug was estimated using these values. Activated charcoal modified the bioavailability of diphenoxylate hydrochloride in vivo. The antipropulsive action of diphenoxylate in the mouse was strongly inhibited in the presence of activated charcoal. A comparative evaluation of charcoal and chromium oxide used as inert, nonabsorbable markers revealed that chromium oxide may be the marker of choic in GI transit studies in laboratory animals since it does not influence the bioavailability of diphenoxylate hydrochloride."}
{"id": "PMID:486", "title": "Binding of bile acids to cholestyramine at gastric pH conditions.", "content": "The binding of bile salts to cholestyramine was studied under varying conditions of pH and added electrolyte. The taurine-conjugated bile salts were strongly absorbed by the anion-exchange resin at low pH and in the presence of chloride anions. Glycocholic acid binding was very weak at low pH but increased strongly with increasing pH. The presence of chloride ions strongly decreased the amount of glycocholate bound by the anion-exchange resin.", "contents": "Binding of bile acids to cholestyramine at gastric pH conditions. The binding of bile salts to cholestyramine was studied under varying conditions of pH and added electrolyte. The taurine-conjugated bile salts were strongly absorbed by the anion-exchange resin at low pH and in the presence of chloride anions. Glycocholic acid binding was very weak at low pH but increased strongly with increasing pH. The presence of chloride ions strongly decreased the amount of glycocholate bound by the anion-exchange resin."}
{"id": "PMID:488", "title": "Amodiaquin accumulation by mouse erythrocytes infected with Plasmodium berghei.", "content": "[14C]amodiaquin accumulation by washed erythrocyte preparations was characterized to permit comparisons with chloroquine accumulation. Erythrocytes infected with Plasmodium berghei CS (chloroquine-susceptible) accumulate amodiaquin by a saturable process that has an apparent dissociation constant for amodiaquin of 7.6 X 10(-8) M and is competitively inhibited by chloroquine, quinine and quinacrine, as is the process of chloroquine accumulation. Within experimental error, the K1 of 8 X 10(-7) M estimated for chloroquine is the same regardless of whether the drug being accumulated is [14C]amodiaquin or [14C]chloroquine. Likewise, the K1 for amodiaquin is the same regardless of which drug is being accumulated. In addition, glucose stimulates and hydrogen ion, cold or interruption of glycolysis inhibits amodiaquin as well as chloroquine accumulation. These findings are evidence that a single process serves to accumulate both drugs. In the absence of substrate, erythrocytes infected with P. berghei CR (chloroquine-resistant) accumulate twice as much amodiaquin as chloroquine, and they accumulate more amodiaquin than do erythrocytes infected with P. berghei CS. These differences occur because P. berghei CR infects polychromatophilic erythrocytes possessing a high-affinity, substrate-independent process of accumulation to which amodiaquin has greater access than chloroquine. In the presence of glucose, amodiaquin accumulation by erythrocytes infected with P. berghei CR, when plotted as a function of amodiaquin concentration in the medium, describes a sigmoid curve.", "contents": "Amodiaquin accumulation by mouse erythrocytes infected with Plasmodium berghei. [14C]amodiaquin accumulation by washed erythrocyte preparations was characterized to permit comparisons with chloroquine accumulation. Erythrocytes infected with Plasmodium berghei CS (chloroquine-susceptible) accumulate amodiaquin by a saturable process that has an apparent dissociation constant for amodiaquin of 7.6 X 10(-8) M and is competitively inhibited by chloroquine, quinine and quinacrine, as is the process of chloroquine accumulation. Within experimental error, the K1 of 8 X 10(-7) M estimated for chloroquine is the same regardless of whether the drug being accumulated is [14C]amodiaquin or [14C]chloroquine. Likewise, the K1 for amodiaquin is the same regardless of which drug is being accumulated. In addition, glucose stimulates and hydrogen ion, cold or interruption of glycolysis inhibits amodiaquin as well as chloroquine accumulation. These findings are evidence that a single process serves to accumulate both drugs. In the absence of substrate, erythrocytes infected with P. berghei CR (chloroquine-resistant) accumulate twice as much amodiaquin as chloroquine, and they accumulate more amodiaquin than do erythrocytes infected with P. berghei CS. These differences occur because P. berghei CR infects polychromatophilic erythrocytes possessing a high-affinity, substrate-independent process of accumulation to which amodiaquin has greater access than chloroquine. In the presence of glucose, amodiaquin accumulation by erythrocytes infected with P. berghei CR, when plotted as a function of amodiaquin concentration in the medium, describes a sigmoid curve."}
{"id": "PMID:489", "title": "The neurochemistry of Parkinson's disease: effect of L-dopa therapy.", "content": "Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as \"good responders\" as compared to \"poor responders.\" Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum.", "contents": "The neurochemistry of Parkinson's disease: effect of L-dopa therapy. Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as \"good responders\" as compared to \"poor responders.\" Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum."}
{"id": "PMID:490", "title": "Studies on the mechanism of depletion of striatal dopamine by alpha-methyl-m-tyrosine.", "content": "These experiments were designed to study the mechanism of depletion of dopamine (DA) in the striatum produced by alpha-methyl-m-tyrosine (alpha-MMT). alpha-Methyl-m-tyramine (alpha-MMTA), the metabolite of alpha-MMT, appears to be the active DA-depleting agent, since the administration of a decarboxylase inhibitor before alpha-MMT markedly reduced both the formation of alpha-MMTA and the depletion of DA. After injection of alpha-MMT (100 mg/kg i.p.), the striatal concentration of homovanillic acid (HVA) rose by 41% at 1 hour. This is probably due to an increase in DA metabolism, since alpha-MMT markedly enhanced the decline of DA produced by alpha-methyl-p-tyrosine (alpha-MPT). At 2, 3 and 4 hours after alpha-MMT, the concentration of HVA and dihydroxyphenylacetic acid was below control level. The decrease in dihydroxyphenylacetic acid is due partially to a decreased formation of dihydroxyphenylacetic acid from DA. In striatal slices, both alpha-MMT and alpha-MMTA decreased the formation of 3H-H2O and the accumulation of 3H-DA from 1-3,5-3H-tyrosine. Alpha-MMT did not alter the specific activity of 3H-tyrosine or release 3H-DA from the slices, but it did inhibit the activity of tyrosine hydroxylase in striatal homogenates at low concentrations of tyrosine (10 muM). Alpha-MMTA released both newly synthesized and exogenously accumulated 3H-DA from striatal slices. At low concentrations of alpha-MMTA, the percent reduction in 3H-H2O was much greater than the percentage of 3H-DA released into the medium. However, at higher concentrations, the inhibition of 3H-H2O reached a maximum while 3H-DA release kept increasing. These results suggest that both inhibition of tyrosine hydroxylase activity and DA release from storage sites by alpha-MMTA may account for the depletion of DA produced by the injection of alpha-MMT.", "contents": "Studies on the mechanism of depletion of striatal dopamine by alpha-methyl-m-tyrosine. These experiments were designed to study the mechanism of depletion of dopamine (DA) in the striatum produced by alpha-methyl-m-tyrosine (alpha-MMT). alpha-Methyl-m-tyramine (alpha-MMTA), the metabolite of alpha-MMT, appears to be the active DA-depleting agent, since the administration of a decarboxylase inhibitor before alpha-MMT markedly reduced both the formation of alpha-MMTA and the depletion of DA. After injection of alpha-MMT (100 mg/kg i.p.), the striatal concentration of homovanillic acid (HVA) rose by 41% at 1 hour. This is probably due to an increase in DA metabolism, since alpha-MMT markedly enhanced the decline of DA produced by alpha-methyl-p-tyrosine (alpha-MPT). At 2, 3 and 4 hours after alpha-MMT, the concentration of HVA and dihydroxyphenylacetic acid was below control level. The decrease in dihydroxyphenylacetic acid is due partially to a decreased formation of dihydroxyphenylacetic acid from DA. In striatal slices, both alpha-MMT and alpha-MMTA decreased the formation of 3H-H2O and the accumulation of 3H-DA from 1-3,5-3H-tyrosine. Alpha-MMT did not alter the specific activity of 3H-tyrosine or release 3H-DA from the slices, but it did inhibit the activity of tyrosine hydroxylase in striatal homogenates at low concentrations of tyrosine (10 muM). Alpha-MMTA released both newly synthesized and exogenously accumulated 3H-DA from striatal slices. At low concentrations of alpha-MMTA, the percent reduction in 3H-H2O was much greater than the percentage of 3H-DA released into the medium. However, at higher concentrations, the inhibition of 3H-H2O reached a maximum while 3H-DA release kept increasing. These results suggest that both inhibition of tyrosine hydroxylase activity and DA release from storage sites by alpha-MMTA may account for the depletion of DA produced by the injection of alpha-MMT."}
{"id": "PMID:491", "title": "Characteristics of gastric inhibition by acidification of oxyntic gland area.", "content": "1. Gastric acid responses to the test meals were measured in the Heidenhain pouch, gastric and pancreatic fistula dogs, using the intragastric titration method, and monitoring the rate at which a solution of 1-0 N-NaOH had to be added to maintain the pH of the gastric content constant at pre-selected values ranging from 5-0 to 1-0. In this way the pH profile of the gastric acid and pepsin responses to a liver extract meal kept in the Heidenhain pouch or gastric fistula as well as to exogenous stimuli such as histamine, pentagastrin or Urecholine could be determined. 2. A liver extract meal adjusted to pH 5-0 produced a potent and pressure-related stimulation of acid secretion from the Heidenhain pouch without any change in secretion from the main stomach and pancreas or in the serum concentration of immuno-assayable gastrin. 3. Graded decrease of the liver extract meal pH to below 5-0 resulted in the pH-dependent inhibition of gastric acid output, which at pH 1-0 was only about 30% of the value attained at pH 5-0. Acid secretion from the Heidenhain pouch induced by exogenous stimuli such as histamine, pentagastrin or Urecholine also showed gradual decrease when the pH of the pouch content was decreased in sequential order from 5-0 to 1-0. This pH-dependent inhibition was accompanied by an increase in pepsin secretion. 4. The pH-dependent inhibition of the Heidenhain pouch response to the liver extract meal was not altered by topical application of a local anaesthetic and atropine or by the intravenous infusion of large doses of atropine, secretin or metiamide, which were shown to cause a marked inhibition of the main stomach response to the liver meal. 5. The results indicate that there is a local and gastrin-independent inhibition mechanism of gastric acid secretion activated by an acidified meal making contact with the oxyntic gland area.", "contents": "Characteristics of gastric inhibition by acidification of oxyntic gland area. 1. Gastric acid responses to the test meals were measured in the Heidenhain pouch, gastric and pancreatic fistula dogs, using the intragastric titration method, and monitoring the rate at which a solution of 1-0 N-NaOH had to be added to maintain the pH of the gastric content constant at pre-selected values ranging from 5-0 to 1-0. In this way the pH profile of the gastric acid and pepsin responses to a liver extract meal kept in the Heidenhain pouch or gastric fistula as well as to exogenous stimuli such as histamine, pentagastrin or Urecholine could be determined. 2. A liver extract meal adjusted to pH 5-0 produced a potent and pressure-related stimulation of acid secretion from the Heidenhain pouch without any change in secretion from the main stomach and pancreas or in the serum concentration of immuno-assayable gastrin. 3. Graded decrease of the liver extract meal pH to below 5-0 resulted in the pH-dependent inhibition of gastric acid output, which at pH 1-0 was only about 30% of the value attained at pH 5-0. Acid secretion from the Heidenhain pouch induced by exogenous stimuli such as histamine, pentagastrin or Urecholine also showed gradual decrease when the pH of the pouch content was decreased in sequential order from 5-0 to 1-0. This pH-dependent inhibition was accompanied by an increase in pepsin secretion. 4. The pH-dependent inhibition of the Heidenhain pouch response to the liver extract meal was not altered by topical application of a local anaesthetic and atropine or by the intravenous infusion of large doses of atropine, secretin or metiamide, which were shown to cause a marked inhibition of the main stomach response to the liver meal. 5. The results indicate that there is a local and gastrin-independent inhibition mechanism of gastric acid secretion activated by an acidified meal making contact with the oxyntic gland area."}
{"id": "PMID:492", "title": "The influence of pH on equilibrium effects of tetrodotoxin on myelinated nerve fibres of Rana esculenta.", "content": "1. The experiments were done on single nodes of Ranvier of Rana esculenta. The effects of tetrodotoxin and H ions were determined either by the reduction of the maximum rate of rise, VA, of action potentials evoked with threshold stimuli or in the voltage clamp by the decrease of the peak Na permeability, PNa. 2. With the tetrodotoxin sample used throughout the investigation the equilibrium dissociation constant, KT, of the toxin-receptor reaction at neutral pH was determined to be 2-8 nM. Between 1-55 and 15-5 nM tetrodotoxin the normalized value, A, of VA, was found to be related to the normalized toxin concentration cT = [TTX]/2-8 nM by the empirical equation log [(1-A)/A] = 1-22 log cT-0-573. 3. On increasing the pH (up to 8-8) the effect of tetrodotoxin diminished as revealed by an increase in A. The apparent reduction of cT (as calculated from A) suggests that the toxin is active only in its cationic forms. 4. Weakly acid tetrodotoxin solutions (7-3 less than pH less than or equal to 5-5) reduced A to a lesser degree than did neutral toxin solutions in spite of the inherent depressing effect of acid pH on A (A = 0-5 at about pH 5-5). In more acid toxin solutions A decreased again and at pH 4-6 it was about equal to the value in toxin-free solution. 5. When, after equilibrium in an acid toxin solution, the perfusate was suddenly changed to neutral Ringer solution A jumped to a higher value A' as measured 1 sec after the switch. Since the blocking effect of hydrogen ions subsided within a fraction of a second while the time constant of the toxin washout is of the order of 1 min, A' reflects the number of Na channels blocked by tetrodotoxin at acid pH. 6. In acid toxin-free solution the peak PNa as obtained in voltage clamp experiments was reduced by a voltage-dependent factor (cH + 1)-1 with CH = [H+]/KH(E) and KH(E) = 2-04 muM exp (0-34 EF/RT). Adding tetrodotoxin resulted in another reduction by a constant factor p'T. 7. Experiments employing various combinations of toxin concentration (3-1-93 nM) and pH values (7-3-5-2) confirm the decreased toxin effect at low pH. Moreover, p'T was smaller (the additional toxin effect larger) when the membrane had been kept depolarized and thus cH reduced during equilibration. This suggests that tetrodotoxin cations and H ions compete for the same blocking site. A quantitative fit, however, requires additional assumptions.", "contents": "The influence of pH on equilibrium effects of tetrodotoxin on myelinated nerve fibres of Rana esculenta. 1. The experiments were done on single nodes of Ranvier of Rana esculenta. The effects of tetrodotoxin and H ions were determined either by the reduction of the maximum rate of rise, VA, of action potentials evoked with threshold stimuli or in the voltage clamp by the decrease of the peak Na permeability, PNa. 2. With the tetrodotoxin sample used throughout the investigation the equilibrium dissociation constant, KT, of the toxin-receptor reaction at neutral pH was determined to be 2-8 nM. Between 1-55 and 15-5 nM tetrodotoxin the normalized value, A, of VA, was found to be related to the normalized toxin concentration cT = [TTX]/2-8 nM by the empirical equation log [(1-A)/A] = 1-22 log cT-0-573. 3. On increasing the pH (up to 8-8) the effect of tetrodotoxin diminished as revealed by an increase in A. The apparent reduction of cT (as calculated from A) suggests that the toxin is active only in its cationic forms. 4. Weakly acid tetrodotoxin solutions (7-3 less than pH less than or equal to 5-5) reduced A to a lesser degree than did neutral toxin solutions in spite of the inherent depressing effect of acid pH on A (A = 0-5 at about pH 5-5). In more acid toxin solutions A decreased again and at pH 4-6 it was about equal to the value in toxin-free solution. 5. When, after equilibrium in an acid toxin solution, the perfusate was suddenly changed to neutral Ringer solution A jumped to a higher value A' as measured 1 sec after the switch. Since the blocking effect of hydrogen ions subsided within a fraction of a second while the time constant of the toxin washout is of the order of 1 min, A' reflects the number of Na channels blocked by tetrodotoxin at acid pH. 6. In acid toxin-free solution the peak PNa as obtained in voltage clamp experiments was reduced by a voltage-dependent factor (cH + 1)-1 with CH = [H+]/KH(E) and KH(E) = 2-04 muM exp (0-34 EF/RT). Adding tetrodotoxin resulted in another reduction by a constant factor p'T. 7. Experiments employing various combinations of toxin concentration (3-1-93 nM) and pH values (7-3-5-2) confirm the decreased toxin effect at low pH. Moreover, p'T was smaller (the additional toxin effect larger) when the membrane had been kept depolarized and thus cH reduced during equilibration. This suggests that tetrodotoxin cations and H ions compete for the same blocking site. A quantitative fit, however, requires additional assumptions."}
{"id": "PMID:493", "title": "The influence of pH on the rate of tetrodotoxin action on myelinated nerve fibres.", "content": "1. The experiments were done on single myelinated nerve fibres of Rana esculenta. The rates of toxin effect were studied either by measuring the maximum rate of rise, VA, of repetitively evoked action potentials or by measuring Na currents during periodic impulses in the voltage clamp. 2. VA measurements showed that in alkaline solutions (pH up to 8-8) the offset rate was unchanged while the onset was slowed in quantitative agreement with an assumed decrease in the active cationic form of tetrodotoxin. 3. Both VA measurements and those in the voltage clamp revealed a decrease in T'off, the offset time constant and in increase in the onset time constant, T'on, as the pH was lowered. 4. For tetrodotoxin concentrations, [TTX], up to 400 nM and pH values down to 5-3 the simple relation T'on/T'off = p'R held, where p'T is the constant factor by which the Na permeability was reduced at equilibrium with a given [TTX]. 5. The agreement between kinetic and equilibrium results was also valid when, at constant [TTX] and pH. p'T was modified by the holding potential during equilibration. 6. No unequivocal explanation of the results can be given but some of their features resemble acid catalysis.", "contents": "The influence of pH on the rate of tetrodotoxin action on myelinated nerve fibres. 1. The experiments were done on single myelinated nerve fibres of Rana esculenta. The rates of toxin effect were studied either by measuring the maximum rate of rise, VA, of repetitively evoked action potentials or by measuring Na currents during periodic impulses in the voltage clamp. 2. VA measurements showed that in alkaline solutions (pH up to 8-8) the offset rate was unchanged while the onset was slowed in quantitative agreement with an assumed decrease in the active cationic form of tetrodotoxin. 3. Both VA measurements and those in the voltage clamp revealed a decrease in T'off, the offset time constant and in increase in the onset time constant, T'on, as the pH was lowered. 4. For tetrodotoxin concentrations, [TTX], up to 400 nM and pH values down to 5-3 the simple relation T'on/T'off = p'R held, where p'T is the constant factor by which the Na permeability was reduced at equilibrium with a given [TTX]. 5. The agreement between kinetic and equilibrium results was also valid when, at constant [TTX] and pH. p'T was modified by the holding potential during equilibration. 6. No unequivocal explanation of the results can be given but some of their features resemble acid catalysis."}
{"id": "PMID:494", "title": "The formation of synapses in amphibian striated muscle during development.", "content": "1. A study has been made of the formation of synapses in developing reinnervated and cross-reinnervated amphibian twitch muscles which receive either a focal (iliofibularis) or a distributed (sartorius) innervation from 'en plaque' nerve terminals using histological, ultrastructural and electrophysiological techniques. 2. During the development of the tadpole through metamorphosis to the adult frog, the sartorius myofibres increased in length at about twice the rate of the iliofibularis myofibres, due to a fast rate of growth at their insertions on to the pelvic tendon. 3. The short iliofibularis and sartorius myofibres of young tadpoles (800 mum long) possessed only a single synapse and the iliofibularis myofibres did not receive any further innervation during development. However the sartorius myofibres received further transient innervation on the new muscle laid down during development at the fast growing pelvic insertion, until the distance between the original synapse formed on the myofibres and the synapse at the pelvic end of the muscle was about 12 mm. 4. During development synapses possessed either skewed, multimodal, or unimodal m.e.p.p. amplitude-frequency distributions; the intervals between m.e.p.p.s. were not distributed randomly according to a Poisson process, as m.e.p.p.s. of similar amplitudes tended to be separated by very short intervals; the unit-size e.p.p. had a similar amplitude-frequency distribution as the m.e.p.p.s. if these had a unimodal distribution. 5. Reinnervation or cross-reinnervation of the sartorius and the iliofibularis muscles in adults or at a late stage of development simply reconstituted the normal focal and distributed innervation patterns of the muscles, as found in the control muscles of the contralateral and unoperated legs. 6. These observations on synapse formation in amphibia are consistent with the hypothesis that during development the axon making the initial synaptic contact on the muscle cells induces a property over a length of muscle membrane adjacent to this site which makes it refractory to synapse formation; thus during reinnervation or cross-reinnervation of adult muscles this refractory property constrains synapse formation to these sites.", "contents": "The formation of synapses in amphibian striated muscle during development. 1. A study has been made of the formation of synapses in developing reinnervated and cross-reinnervated amphibian twitch muscles which receive either a focal (iliofibularis) or a distributed (sartorius) innervation from 'en plaque' nerve terminals using histological, ultrastructural and electrophysiological techniques. 2. During the development of the tadpole through metamorphosis to the adult frog, the sartorius myofibres increased in length at about twice the rate of the iliofibularis myofibres, due to a fast rate of growth at their insertions on to the pelvic tendon. 3. The short iliofibularis and sartorius myofibres of young tadpoles (800 mum long) possessed only a single synapse and the iliofibularis myofibres did not receive any further innervation during development. However the sartorius myofibres received further transient innervation on the new muscle laid down during development at the fast growing pelvic insertion, until the distance between the original synapse formed on the myofibres and the synapse at the pelvic end of the muscle was about 12 mm. 4. During development synapses possessed either skewed, multimodal, or unimodal m.e.p.p. amplitude-frequency distributions; the intervals between m.e.p.p.s. were not distributed randomly according to a Poisson process, as m.e.p.p.s. of similar amplitudes tended to be separated by very short intervals; the unit-size e.p.p. had a similar amplitude-frequency distribution as the m.e.p.p.s. if these had a unimodal distribution. 5. Reinnervation or cross-reinnervation of the sartorius and the iliofibularis muscles in adults or at a late stage of development simply reconstituted the normal focal and distributed innervation patterns of the muscles, as found in the control muscles of the contralateral and unoperated legs. 6. These observations on synapse formation in amphibia are consistent with the hypothesis that during development the axon making the initial synaptic contact on the muscle cells induces a property over a length of muscle membrane adjacent to this site which makes it refractory to synapse formation; thus during reinnervation or cross-reinnervation of adult muscles this refractory property constrains synapse formation to these sites."}
{"id": "PMID:495", "title": "Comparative studies of Trypanosoma vespertilionis Battaglia and Trypanosoma dionisii Bettencourt & Fran\u00e7a.", "content": "In diphasic blood agar media Trypanosoma vespertilionis developed spheroid clusters as compared to rather long, sausage-shaped (sometimes branched) clusters formed by Trypanosoma dionisii. The former species attained a greater population density (approximately 6 X 10(7) organisms/ml) than the latter (approximately 2 X 10(7) organisms/ml). Greater numbers of epimastigotes, some in active binary divisions, were observed during the logarithmic phase of growth, and morphologic changes occurred during cultivation which correlated with increased acidity and a depletion of glucose. Maximum numbers of trypomastigote forms were found during the stationary and early death phases. Most of the forms observed after 20 days were sphaeromastigotes. Glucose concentrations decreased to 0 M in T. vespertilionis and to 4.4 X 10(-5) M in T. dionisii cultures during the stationary and death phases. By the 12th day of incubation cultures of T. vespertilionis were more acid (pH 5.5) than those of T. dionisii vespertilionis and T. dionisii contained common and specific antigens. At least 2-3 common antigens were detected in extracts reacted against heterologous antisera. Specific antigens were observed as nonidentical lines formed by extracts reacted against homologous and heterologous antisera and with antisera absorbed with heterologous antigens. At least 2 specific antigens were evident in extracts of T. vespertilionis and 1 in extracts of T. dionisii.", "contents": "Comparative studies of Trypanosoma vespertilionis Battaglia and Trypanosoma dionisii Bettencourt & Fran\u00e7a. In diphasic blood agar media Trypanosoma vespertilionis developed spheroid clusters as compared to rather long, sausage-shaped (sometimes branched) clusters formed by Trypanosoma dionisii. The former species attained a greater population density (approximately 6 X 10(7) organisms/ml) than the latter (approximately 2 X 10(7) organisms/ml). Greater numbers of epimastigotes, some in active binary divisions, were observed during the logarithmic phase of growth, and morphologic changes occurred during cultivation which correlated with increased acidity and a depletion of glucose. Maximum numbers of trypomastigote forms were found during the stationary and early death phases. Most of the forms observed after 20 days were sphaeromastigotes. Glucose concentrations decreased to 0 M in T. vespertilionis and to 4.4 X 10(-5) M in T. dionisii cultures during the stationary and death phases. By the 12th day of incubation cultures of T. vespertilionis were more acid (pH 5.5) than those of T. dionisii vespertilionis and T. dionisii contained common and specific antigens. At least 2-3 common antigens were detected in extracts reacted against heterologous antisera. Specific antigens were observed as nonidentical lines formed by extracts reacted against homologous and heterologous antisera and with antisera absorbed with heterologous antigens. At least 2 specific antigens were evident in extracts of T. vespertilionis and 1 in extracts of T. dionisii."}
{"id": "PMID:496", "title": "The use of psychotropic drugs in general practice. A report of a year's survey.", "content": "All the psychotropic tablets prescribed by a general practitioner in one year are itemised. The patients who received them are separated into diagnostic groups and their treatment is analysed by the number of attendances, prescriptions, and duration of therapy. Hospital referrals and overdoses over a longer period are recorded. My policy in psychiatric conditions is indicated.", "contents": "The use of psychotropic drugs in general practice. A report of a year's survey. All the psychotropic tablets prescribed by a general practitioner in one year are itemised. The patients who received them are separated into diagnostic groups and their treatment is analysed by the number of attendances, prescriptions, and duration of therapy. Hospital referrals and overdoses over a longer period are recorded. My policy in psychiatric conditions is indicated."}
{"id": "PMID:497", "title": "N-Isopropyl derivatives of dopamine and 5,6-dihydroxy-2-aminotetralin.", "content": "Secondary and tertiary amino homologs of the title compounds have been prepared, bearing an N-isopropyl group. In peripheral evaluation, certain members of the series exhibited beta-adrenergic agonist effects of lower activity than isoproterenol. N-Methyl-N-isopropyl-5,6-dihydroxytetralin exhibited marked properties consistent with its being an alpha agonist, and it is concluded that introduction of considerable bulk about the nitrogen of a catecholamine does not a priori destroy alpha-agonist effects. The compounds qualitatively paralleled the effects of dopamine in assays based upon direct intrastriatal administration in rats, although they were less potent than dopamine.", "contents": "N-Isopropyl derivatives of dopamine and 5,6-dihydroxy-2-aminotetralin. Secondary and tertiary amino homologs of the title compounds have been prepared, bearing an N-isopropyl group. In peripheral evaluation, certain members of the series exhibited beta-adrenergic agonist effects of lower activity than isoproterenol. N-Methyl-N-isopropyl-5,6-dihydroxytetralin exhibited marked properties consistent with its being an alpha agonist, and it is concluded that introduction of considerable bulk about the nitrogen of a catecholamine does not a priori destroy alpha-agonist effects. The compounds qualitatively paralleled the effects of dopamine in assays based upon direct intrastriatal administration in rats, although they were less potent than dopamine."}
{"id": "PMID:506", "title": "Phospholipases. III. Effects of ionic surfactants on the phospholipase-catalyzed hydrolysis of unsonicated egg lecithin liposomes.", "content": "Apparent values of Km and Vmax have been measured for catalysis of hydrolysis of unsonicated egg lecithin liposomes, activated through addition of 0.4 M n-hexanol, by phospholipases A2 from bee and snake venoms and by phospholipase C from Clostridium welchii as a function of the concentration of three surfactants: hexadecylamine, hexadecyltrimethylammonium bromide, and dihexadecyl phosphate. For all three enzymes, values of Km and Vmax show little or no dependence on the concentration of these ionic surfactants, demonstrating that the liposomal surface charge is not a crucial factor in determining susceptibility to phospholipase-catalyzed hydrolysis.", "contents": "Phospholipases. III. Effects of ionic surfactants on the phospholipase-catalyzed hydrolysis of unsonicated egg lecithin liposomes. Apparent values of Km and Vmax have been measured for catalysis of hydrolysis of unsonicated egg lecithin liposomes, activated through addition of 0.4 M n-hexanol, by phospholipases A2 from bee and snake venoms and by phospholipase C from Clostridium welchii as a function of the concentration of three surfactants: hexadecylamine, hexadecyltrimethylammonium bromide, and dihexadecyl phosphate. For all three enzymes, values of Km and Vmax show little or no dependence on the concentration of these ionic surfactants, demonstrating that the liposomal surface charge is not a crucial factor in determining susceptibility to phospholipase-catalyzed hydrolysis."}
{"id": "PMID:507", "title": "Negative potential level in the outer layer of the toad skin.", "content": "The isolated skin of the toad Bufo marinus ictericus when impaled from the outer surface by glass microelectrodes filled with 3 M KCl shows a voltage profile which is a continuous function of the depth of impalement. The superficial intraepithelial potential difference measured with reference to the external solution (PDi) is negative with NaCl-Ringer's solution on both sides of the skin, displaying a minimum of -26.7+/-3.6 mV at 6+/-2 mum. Null value is obtained at 19+/-3 mum, with positive values for deeper impalements. Indications of cell impalements (abrupt voltage and resistance jumps) were frequently observed at sites deeper than 25 mum from the outer surface. Measurements of the electrical resistance between the microelectrode and the external solution, made with single- and double-barreled microelectrodes, showed great discrepancies, which may be attributed to distinct pathways of different resistances in the stratum corneum. PDi measured at a depth of 5 mum was a logarithmic function of Na2SO4 or K2SO4 concentration in the external solution, increasing in negativity with a reduction in concentration. Substitution of Na by K in the external solution had only minor effects on PDi. Acidification of the external solution from pH 9 is accompanied by a reduction in the negative value of PDi. At pH 3 PDi was positive. PDi was interpreted as a diffusion potential at the tip of the microelectrode due to KCl diffusion from the electrode into the matrix of the stratum corneum. Differences in K and Cl mobilities, responsible for the origin of PDi, were attributed to fixed charges in the matrix of the stratum corneum, with density and polarity determined by their degree of proponation, controlled by the hydrogen ion concentration of the external solution. Skin potential, short-circuit current and their relationship to PDI were discussed.", "contents": "Negative potential level in the outer layer of the toad skin. The isolated skin of the toad Bufo marinus ictericus when impaled from the outer surface by glass microelectrodes filled with 3 M KCl shows a voltage profile which is a continuous function of the depth of impalement. The superficial intraepithelial potential difference measured with reference to the external solution (PDi) is negative with NaCl-Ringer's solution on both sides of the skin, displaying a minimum of -26.7+/-3.6 mV at 6+/-2 mum. Null value is obtained at 19+/-3 mum, with positive values for deeper impalements. Indications of cell impalements (abrupt voltage and resistance jumps) were frequently observed at sites deeper than 25 mum from the outer surface. Measurements of the electrical resistance between the microelectrode and the external solution, made with single- and double-barreled microelectrodes, showed great discrepancies, which may be attributed to distinct pathways of different resistances in the stratum corneum. PDi measured at a depth of 5 mum was a logarithmic function of Na2SO4 or K2SO4 concentration in the external solution, increasing in negativity with a reduction in concentration. Substitution of Na by K in the external solution had only minor effects on PDi. Acidification of the external solution from pH 9 is accompanied by a reduction in the negative value of PDi. At pH 3 PDi was positive. PDi was interpreted as a diffusion potential at the tip of the microelectrode due to KCl diffusion from the electrode into the matrix of the stratum corneum. Differences in K and Cl mobilities, responsible for the origin of PDi, were attributed to fixed charges in the matrix of the stratum corneum, with density and polarity determined by their degree of proponation, controlled by the hydrogen ion concentration of the external solution. Skin potential, short-circuit current and their relationship to PDI were discussed."}
{"id": "PMID:508", "title": "The avian erythrocyte: a study of fixation for electron microscopy.", "content": "The quality of ultrastructural preservation of the avian erythrocyte achieved using various fixation techniques is evaluated. Different combinations of initial fixatives, buffers and post-fixation procedures were tested as well as variations in fixative osmolarity, pH and temperature. Of the commonly used initial fixatives (glutaraldehyde, acrolein and formaldehyde), 2% glutaraldehyde, alone in a slightly hypertonic buffer containing divalent ions, produced optimum erythrocyte preservation. The osmolarity was balanced using a non-electrolyte such as a sucrose. The addition of 12% hexylene glycol to the buffer solutions also improves erythrocyte preservation, as evidenced by the increased stability of the marginal microtubules, microfilaments and proteinaceous material. The use of Spurr low-viscosity epoxy resin enables the cells to be collected using low gravitational centrifugation.", "contents": "The avian erythrocyte: a study of fixation for electron microscopy. The quality of ultrastructural preservation of the avian erythrocyte achieved using various fixation techniques is evaluated. Different combinations of initial fixatives, buffers and post-fixation procedures were tested as well as variations in fixative osmolarity, pH and temperature. Of the commonly used initial fixatives (glutaraldehyde, acrolein and formaldehyde), 2% glutaraldehyde, alone in a slightly hypertonic buffer containing divalent ions, produced optimum erythrocyte preservation. The osmolarity was balanced using a non-electrolyte such as a sucrose. The addition of 12% hexylene glycol to the buffer solutions also improves erythrocyte preservation, as evidenced by the increased stability of the marginal microtubules, microfilaments and proteinaceous material. The use of Spurr low-viscosity epoxy resin enables the cells to be collected using low gravitational centrifugation."}
{"id": "PMID:514", "title": "Hemoglobin solution and the oxyhemoglobin dissociation curve.", "content": "1) A study was carried out to determine the oxyhemoglobin dissociation curve of stroma-free hemoglobin solution and factors which influence it, (pH; 2,3 DPG). 2) To simulate acute volume replacement, dilution experiments, in vitro, were performed employing both hemoglobin solution and Ringer's lactate in whole blood. 3) It was determined that stroma-free hemoglobin solution has a left-shifted oxyhemoglobin dissociation curve which responds to pH change but not to the addition of 2,3 DPG. 4) The dilutional effect of hemoglobin solution when mixed with whole blood in volumes up to 50% was to left-shift the oxyhemoglobin curve, unlike the effect of Ringer's lactate (no change). 5) This may have importance in the hemodynamic compensatory response to acute normovolemic anemia.", "contents": "Hemoglobin solution and the oxyhemoglobin dissociation curve. 1) A study was carried out to determine the oxyhemoglobin dissociation curve of stroma-free hemoglobin solution and factors which influence it, (pH; 2,3 DPG). 2) To simulate acute volume replacement, dilution experiments, in vitro, were performed employing both hemoglobin solution and Ringer's lactate in whole blood. 3) It was determined that stroma-free hemoglobin solution has a left-shifted oxyhemoglobin dissociation curve which responds to pH change but not to the addition of 2,3 DPG. 4) The dilutional effect of hemoglobin solution when mixed with whole blood in volumes up to 50% was to left-shift the oxyhemoglobin curve, unlike the effect of Ringer's lactate (no change). 5) This may have importance in the hemodynamic compensatory response to acute normovolemic anemia."}
{"id": "PMID:515", "title": "Effect of antihistamine-antiserotonin and ganglionic blocking agents upon increased capillary permeability following burn trauma.", "content": "Tiny (0.2% TBS), partial thickness, non-contact radiant heat burns in guinea pigs resulted, within 3 hours, in significant edema formation and protein leakage at the site of the injury. Areas of skin distant to the burn also showed an increase in water content but no protein leakage. Pretreatment of the animals with either chlorisondamine hydrochloride or a mixture of methysergide and chlorpheniramine significantly decreased postburn edema formation and protein leakage. Liquid emulsion autoradiography revealed that leakage of protein occurs primarily in the areas of skin adjacent to the panniculus carnosus. The studies suggest that: the increase in vascular permeability that occurs as a consequence of burn injuries is humorally mediated; albumin leakage is limited to the injured tissues; and histamine, serotonin, and presumably catecholamines play significant roles in the development of this phenomenon.", "contents": "Effect of antihistamine-antiserotonin and ganglionic blocking agents upon increased capillary permeability following burn trauma. Tiny (0.2% TBS), partial thickness, non-contact radiant heat burns in guinea pigs resulted, within 3 hours, in significant edema formation and protein leakage at the site of the injury. Areas of skin distant to the burn also showed an increase in water content but no protein leakage. Pretreatment of the animals with either chlorisondamine hydrochloride or a mixture of methysergide and chlorpheniramine significantly decreased postburn edema formation and protein leakage. Liquid emulsion autoradiography revealed that leakage of protein occurs primarily in the areas of skin adjacent to the panniculus carnosus. The studies suggest that: the increase in vascular permeability that occurs as a consequence of burn injuries is humorally mediated; albumin leakage is limited to the injured tissues; and histamine, serotonin, and presumably catecholamines play significant roles in the development of this phenomenon."}
{"id": "PMID:516", "title": "Bacteriophage T4 baseplate components. II. Binding and location of bacteriophage-induced dihydrofolate reductase.", "content": "The location of T4D phage-induced dihydrofolate reductase (dfr) has been determined in intact and incomplete phage particles. It has been found that phage mutants inducing a temperature-sensitive dfr (dfrts) procude heat-labile phage particles. The structural dfr produced by these ts mutants was shown to assume different configurations depending on the temperature at which the phage is assembled. Morphogenesis of incomplete phage particles lacking the gene 11 protein on their baseplates was found to be inhibited by reagents binding to dfr, such as antibodies to dfr. Further, cofactor molecules for dfr, such as reduced nicotinamide adenine dinucleotide phosphate and reduced nicotinamide adenine dinucleotide, also inhibited the step in morphogenesis involving the addition of gene 11 product. On the other hand, inhibitors of dfr, such as adenosine dephosphoribose, stimulated the addition of the gene 11 protein. It has been concluded that the phage-induced dfr is a baseplate component which is partially covered by the gene 11 protein. The properties of phage particles produced after infection of the nonpermissive host with the one known T4D mutant containing a nonsense mutation in its dfr gene suggested that these progeny particles contained a partial polypeptide, which was large enough to serve as a structural element.", "contents": "Bacteriophage T4 baseplate components. II. Binding and location of bacteriophage-induced dihydrofolate reductase. The location of T4D phage-induced dihydrofolate reductase (dfr) has been determined in intact and incomplete phage particles. It has been found that phage mutants inducing a temperature-sensitive dfr (dfrts) procude heat-labile phage particles. The structural dfr produced by these ts mutants was shown to assume different configurations depending on the temperature at which the phage is assembled. Morphogenesis of incomplete phage particles lacking the gene 11 protein on their baseplates was found to be inhibited by reagents binding to dfr, such as antibodies to dfr. Further, cofactor molecules for dfr, such as reduced nicotinamide adenine dinucleotide phosphate and reduced nicotinamide adenine dinucleotide, also inhibited the step in morphogenesis involving the addition of gene 11 product. On the other hand, inhibitors of dfr, such as adenosine dephosphoribose, stimulated the addition of the gene 11 protein. It has been concluded that the phage-induced dfr is a baseplate component which is partially covered by the gene 11 protein. The properties of phage particles produced after infection of the nonpermissive host with the one known T4D mutant containing a nonsense mutation in its dfr gene suggested that these progeny particles contained a partial polypeptide, which was large enough to serve as a structural element."}
{"id": "PMID:517", "title": "Uukuniemi virus contains an RNA polymerase.", "content": "An RNA-dependent RNA polymerase activity has been found associated with Uukuniemi virions. The enzyme activity is expressed only after disrupting the virions with the nonionic detergent Triton X-100 and is absolutely dependent on Mn2+, whereas Mg2+ is not required, a finding that distinguishes this polymerase from those of other enveloped minus-strand RNA viruses. Within the range pH 7.2 to 8.5 no distinct optimum was found. The optimum temperature was between 37 and 40 C. The reaction was not inhibited by actinomycin D, rifampin, or DNase, whereas RNase was completely inhibitory. The partially RNase-resistant product consisted of rather small-sized RNA, which contained sequences complementary to Uukuniemi virus RNA as shown by hybridization to the template L, M, and S RNA species of Uukuniemi virus.", "contents": "Uukuniemi virus contains an RNA polymerase. An RNA-dependent RNA polymerase activity has been found associated with Uukuniemi virions. The enzyme activity is expressed only after disrupting the virions with the nonionic detergent Triton X-100 and is absolutely dependent on Mn2+, whereas Mg2+ is not required, a finding that distinguishes this polymerase from those of other enveloped minus-strand RNA viruses. Within the range pH 7.2 to 8.5 no distinct optimum was found. The optimum temperature was between 37 and 40 C. The reaction was not inhibited by actinomycin D, rifampin, or DNase, whereas RNase was completely inhibitory. The partially RNase-resistant product consisted of rather small-sized RNA, which contained sequences complementary to Uukuniemi virus RNA as shown by hybridization to the template L, M, and S RNA species of Uukuniemi virus."}
{"id": "PMID:519", "title": "Radiographic examination of mandibular lesions in barren-ground caribou.", "content": "Dental anomalies were observed in 43 of 1,226 barren-ground caribou (Rangifer tarandus groenlandicus) taken between 1966 and 1968. In five of these 43 animals, the mandibles had deformities which radiography showed to be the result of dental abscesses in four cases and probably of a trauma in the other. The absence of actinomycotic lesions of the jaw bones of these 1,226 animals, and of more than 500 examined previously, indicates that \"lumpy jaw\" is rare in barren-ground caribou. The authors suggest the use of radiography to determine the nature of bone growth on skeletal remains, in the absence of soft tissues for examination for Actinomyces, either microscopically or by cultural methods.", "contents": "Radiographic examination of mandibular lesions in barren-ground caribou. Dental anomalies were observed in 43 of 1,226 barren-ground caribou (Rangifer tarandus groenlandicus) taken between 1966 and 1968. In five of these 43 animals, the mandibles had deformities which radiography showed to be the result of dental abscesses in four cases and probably of a trauma in the other. The absence of actinomycotic lesions of the jaw bones of these 1,226 animals, and of more than 500 examined previously, indicates that \"lumpy jaw\" is rare in barren-ground caribou. The authors suggest the use of radiography to determine the nature of bone growth on skeletal remains, in the absence of soft tissues for examination for Actinomyces, either microscopically or by cultural methods."}
{"id": "PMID:525", "title": "Experimental diarrhea in cynomolgus monkeys by oral administration with Clostridium perfringens type A viable cells or enterotoxin.", "content": "Purified C. perfringens type A enterotoxin fed orally in an amount of 5 mg caused both vomiting and diarrhea in the monkey only when the gastric juice had been neutralized. Exposure of enterotoxin to pH 4.0 or below rapidly destroyed the activity. All three monkeys receiving sodium bicarbonate and 2.4 X 10(10) viable cells grown in DS medium developed diarrhea, and only one of them vomited once. The diarrhea lasted for 13, 18 and 19 hr. The symptoms were similar to those reported in human cases of C. perfringens food poisoning. These results have verified the general notion that C. perfringens food poisoning should be categorized as a true \"intravital intoxication\". The reversed passive hemagglutination test detected enterotoxin directly in most fecal samples. This method may be applicable for diagnosis of human cases of C. perfringens food poisoning. Neither enterotoxin nor anti-enterotoxin was detected in serum samples taken from any monkey up to 21 days after the challenge. We are tempted to conclude, therefore, that no significant amount of C. perfringens enterotoxin is absorbed from the intestine.", "contents": "Experimental diarrhea in cynomolgus monkeys by oral administration with Clostridium perfringens type A viable cells or enterotoxin. Purified C. perfringens type A enterotoxin fed orally in an amount of 5 mg caused both vomiting and diarrhea in the monkey only when the gastric juice had been neutralized. Exposure of enterotoxin to pH 4.0 or below rapidly destroyed the activity. All three monkeys receiving sodium bicarbonate and 2.4 X 10(10) viable cells grown in DS medium developed diarrhea, and only one of them vomited once. The diarrhea lasted for 13, 18 and 19 hr. The symptoms were similar to those reported in human cases of C. perfringens food poisoning. These results have verified the general notion that C. perfringens food poisoning should be categorized as a true \"intravital intoxication\". The reversed passive hemagglutination test detected enterotoxin directly in most fecal samples. This method may be applicable for diagnosis of human cases of C. perfringens food poisoning. Neither enterotoxin nor anti-enterotoxin was detected in serum samples taken from any monkey up to 21 days after the challenge. We are tempted to conclude, therefore, that no significant amount of C. perfringens enterotoxin is absorbed from the intestine."}
{"id": "PMID:534", "title": "[Effect of peripheral counterpulsation on the body of an animal with intact heart].", "content": "The effect of lasting peripheral counterpulsation upon the haemodynamics and the main biochemical factors of the blood was studied in 14 dogs with intact hearts. In cases of significant tachycardia counterpulsation in a 1:2 regimen results in only a partial reduction of the resistance to the cardiac output. This does not always permit to prevent the formation of the phenomenon of an elevated myocardial contractility. The haemodynamic conditions are most optimal in a 1:1 regimen of counterpulsation. Slowing down of the cardiac rhythm was achieved by means of hypothermia.", "contents": "[Effect of peripheral counterpulsation on the body of an animal with intact heart]. The effect of lasting peripheral counterpulsation upon the haemodynamics and the main biochemical factors of the blood was studied in 14 dogs with intact hearts. In cases of significant tachycardia counterpulsation in a 1:2 regimen results in only a partial reduction of the resistance to the cardiac output. This does not always permit to prevent the formation of the phenomenon of an elevated myocardial contractility. The haemodynamic conditions are most optimal in a 1:1 regimen of counterpulsation. Slowing down of the cardiac rhythm was achieved by means of hypothermia."}
{"id": "PMID:535", "title": "[Regulation of interrelation between pulmonary ventilation and circulation].", "content": "In acute experiments on 92 cats anesthetized with Urethane and kept under controlled respiration the mechanism of tonic activity of the pulmonary vessels was studied in the presence of a decreased partial pressure of oxygen in the alveoli. The tonicity of the pulmonary vessels was recorded during autoperfusion of the vessels of the posterior lobe of the left lung by means of a perfusion pump. Simultaneously, the pressure in the common carotid artery was recorded and the oxygen saturation of the blood was measured. Pharmacological analysis was used for the study of the mechanism of the pressor reaction of the pulmonary vessels under hypoxic hypoxy, and it demonstrated that the pression of the pulmonary vessels that develops under alveolar hypoxy is less distinct under the effect of the ganglioblocking agent Benzo-hexonium, as well as the myotropic agents Papaverine and Chloracizine. The above reaction was significantly inhibited by the blocking agents of the D- and M-serotonin-reactive structures -- Dihydroergothamine, Morphine and Novocain, and it was completely lacking against the background of the action of Izadrine and Dimedrol -- blocking agents of serotonin- and histamine-reactive structures. It can be supposed that the D- and M-serotonin-reactive, and probably also the histamine-reactive structures participate in the regulation of the interrelationship of ventilation and pulmonary circulation.", "contents": "[Regulation of interrelation between pulmonary ventilation and circulation]. In acute experiments on 92 cats anesthetized with Urethane and kept under controlled respiration the mechanism of tonic activity of the pulmonary vessels was studied in the presence of a decreased partial pressure of oxygen in the alveoli. The tonicity of the pulmonary vessels was recorded during autoperfusion of the vessels of the posterior lobe of the left lung by means of a perfusion pump. Simultaneously, the pressure in the common carotid artery was recorded and the oxygen saturation of the blood was measured. Pharmacological analysis was used for the study of the mechanism of the pressor reaction of the pulmonary vessels under hypoxic hypoxy, and it demonstrated that the pression of the pulmonary vessels that develops under alveolar hypoxy is less distinct under the effect of the ganglioblocking agent Benzo-hexonium, as well as the myotropic agents Papaverine and Chloracizine. The above reaction was significantly inhibited by the blocking agents of the D- and M-serotonin-reactive structures -- Dihydroergothamine, Morphine and Novocain, and it was completely lacking against the background of the action of Izadrine and Dimedrol -- blocking agents of serotonin- and histamine-reactive structures. It can be supposed that the D- and M-serotonin-reactive, and probably also the histamine-reactive structures participate in the regulation of the interrelationship of ventilation and pulmonary circulation."}
{"id": "PMID:537", "title": "Multiple cyclic nucleotide phosphodiesterases in rat kidney.", "content": "Using DEAE-cellulose chromatography and Agarose gel filtration we have partially purified a low Km cyclic adenosine monophosphate (AMP) phosphodiesterase from the 100,000 X g supernatant of rat kidneys. The characteristics of this enzyme included a Km of approximately 4 muM a pH optimum of around 8.0 and a requirement for magnesium. This preparation should be suitable for investigation of possible effects of hormones, drugs and cellular constituents on the cyclic AMP pathway through any direct effects on the low Km enzyme. We have also demonstrated a nonspecific, high Km cyclic nucleotide phosphodiesterase and possibly a specific cyclic guanosine monophosphate (GMP) phosphodiesterase in the soluble fraction from rat kidneys.", "contents": "Multiple cyclic nucleotide phosphodiesterases in rat kidney. Using DEAE-cellulose chromatography and Agarose gel filtration we have partially purified a low Km cyclic adenosine monophosphate (AMP) phosphodiesterase from the 100,000 X g supernatant of rat kidneys. The characteristics of this enzyme included a Km of approximately 4 muM a pH optimum of around 8.0 and a requirement for magnesium. This preparation should be suitable for investigation of possible effects of hormones, drugs and cellular constituents on the cyclic AMP pathway through any direct effects on the low Km enzyme. We have also demonstrated a nonspecific, high Km cyclic nucleotide phosphodiesterase and possibly a specific cyclic guanosine monophosphate (GMP) phosphodiesterase in the soluble fraction from rat kidneys."}
{"id": "PMID:538", "title": "Effect on aging on plasma renin and aldosterone in normal man.", "content": "The influence of aging on the renin-angiotensin-aldosterone system was evaluated by comparing young (20 to 30 yr) with elderly (62 to 70 yr) healthy subjects. Despite comparable body sodium-fluid balance in the two age groups, serum renin concentration, plasma renin activity and aldosterone concentrations were lower in the elderly. The age-related decreases in circulating renin and aldosterone concentrations were slight while subjects were supine and receiving normal sodium intake; when upright and during sodium depletion, they were more pronounced. Inverse renin-blood pressure interrelations were noted during two of four study conditions involving normal sodium intake or mild sodium depletion (r = --0.44 and --0.47, respectively), but not during progressive sodium depletion. Plasma renin levels were decreased in the elderly regardless of the presence or absence of an inverse relationship with blood pressure. Aldosterone and cortisol responses to corticotropin infusion were unaltered in the elderly. It is concluded that aging may cause a decrease in circulating renin, with parallel lowering of plasma aldosterone concentrations.", "contents": "Effect on aging on plasma renin and aldosterone in normal man. The influence of aging on the renin-angiotensin-aldosterone system was evaluated by comparing young (20 to 30 yr) with elderly (62 to 70 yr) healthy subjects. Despite comparable body sodium-fluid balance in the two age groups, serum renin concentration, plasma renin activity and aldosterone concentrations were lower in the elderly. The age-related decreases in circulating renin and aldosterone concentrations were slight while subjects were supine and receiving normal sodium intake; when upright and during sodium depletion, they were more pronounced. Inverse renin-blood pressure interrelations were noted during two of four study conditions involving normal sodium intake or mild sodium depletion (r = --0.44 and --0.47, respectively), but not during progressive sodium depletion. Plasma renin levels were decreased in the elderly regardless of the presence or absence of an inverse relationship with blood pressure. Aldosterone and cortisol responses to corticotropin infusion were unaltered in the elderly. It is concluded that aging may cause a decrease in circulating renin, with parallel lowering of plasma aldosterone concentrations."}
{"id": "PMID:540", "title": "[Immune mechanisms in uremia].", "content": "There is both clinical and experimental evidence that cellular and humoral immunity are suppressed in patients with renal insufficiency: observations in organ transplantation and in vitro stimulation of lymphocytes from uraemic patients, investigations of acute and late hypersensitivity reactions, the immune response after active immunization as well as changes of immunoglobulins and lymphatic organs in uraemia are discussed in the paper. The underlying mechanisms are complex and not yet fully understood. Lymphopenia, atrophy of the thymus gland, toxic serum factors, induction of enhancing mechanisms by certain serum fractions and metabolic defects of lymphocytes--all were shown to be involved or at least considered to be. At present, however, it is impossible to define their rank of importance and the exact place they may occupy in the genesis of this type of \"natural immunosuppression\".", "contents": "[Immune mechanisms in uremia]. There is both clinical and experimental evidence that cellular and humoral immunity are suppressed in patients with renal insufficiency: observations in organ transplantation and in vitro stimulation of lymphocytes from uraemic patients, investigations of acute and late hypersensitivity reactions, the immune response after active immunization as well as changes of immunoglobulins and lymphatic organs in uraemia are discussed in the paper. The underlying mechanisms are complex and not yet fully understood. Lymphopenia, atrophy of the thymus gland, toxic serum factors, induction of enhancing mechanisms by certain serum fractions and metabolic defects of lymphocytes--all were shown to be involved or at least considered to be. At present, however, it is impossible to define their rank of importance and the exact place they may occupy in the genesis of this type of \"natural immunosuppression\"."}
{"id": "PMID:541", "title": "Improvement of renin determination in human plasma using a commonly available renin standard in a radioimmunological method.", "content": "A new method for the measurement of renin in human plasma is described. The method is based on the introduction of the internationally available renin standard of the Medical Research Council (MRC) London, as a calibration system. Thus, some principal disadvantages of methods expressing results in renin reaction velocity (angiotensin generation rate) only are avoided. Both renins, unknown and standard, react with a sheep substrate preparation and are handled identically throughout the whole procedure including the angiotensin I radioimmunoassay (RIA). The plasma renin concentration (PRC) is given in 10(-6) MRC-renin units (muM/ml). the renin standard is free of angiotensin, angiotensinases, and angiotensinogen; it is stable on storage. Identical enzyme kinetics are shown for both renins. An interference between endogenous and exogenous substrate could be avoided. The potentially harmful influences of proteins from the enzyme incubation mixture of the RIA dose response curve are shown. The use of an angiotensin I calibration system could be omitted. Using a standard renin dilution from 250-0.9 muU/ml also the full biological range is covered. When giving an unrestricted diet the preliminary normal values of PRC are 21.9 +/- 12.6 muU/ml in recumbent and 40.1 +/- 19.8 muU/ml in upright position (n = 16,x +/- s, age 20-35 years). Earlier findings of age-dependency of PRC were confirmed.", "contents": "Improvement of renin determination in human plasma using a commonly available renin standard in a radioimmunological method. A new method for the measurement of renin in human plasma is described. The method is based on the introduction of the internationally available renin standard of the Medical Research Council (MRC) London, as a calibration system. Thus, some principal disadvantages of methods expressing results in renin reaction velocity (angiotensin generation rate) only are avoided. Both renins, unknown and standard, react with a sheep substrate preparation and are handled identically throughout the whole procedure including the angiotensin I radioimmunoassay (RIA). The plasma renin concentration (PRC) is given in 10(-6) MRC-renin units (muM/ml). the renin standard is free of angiotensin, angiotensinases, and angiotensinogen; it is stable on storage. Identical enzyme kinetics are shown for both renins. An interference between endogenous and exogenous substrate could be avoided. The potentially harmful influences of proteins from the enzyme incubation mixture of the RIA dose response curve are shown. The use of an angiotensin I calibration system could be omitted. Using a standard renin dilution from 250-0.9 muU/ml also the full biological range is covered. When giving an unrestricted diet the preliminary normal values of PRC are 21.9 +/- 12.6 muU/ml in recumbent and 40.1 +/- 19.8 muU/ml in upright position (n = 16,x +/- s, age 20-35 years). Earlier findings of age-dependency of PRC were confirmed."}
{"id": "PMID:542", "title": "[Validity of pH measurements by means of micro pH combination electrodes in blood and other biological fluids (author's transl)].", "content": "pH measurements in blood or in media containing either proteins or polypeptides and performed by means of micro pH combination electrodes type N 58 (Schott & Gen., Mainz) yield in a systematic error according to the regression line y = 1.135 chi - 0.842, in the range between pH 5.3 and 8.3. This deviation from the real pH value is independent of the protein concentration and amounts to 0.1-0.2 pH units in the  physiological range. The error does not occur if the pH measurements are performed in media which are free of proteins and polypeptides, respectively. If the electrolyte solution within the reference electrode is replaced (NaCl solution instead of KCl solution) the error is distinctly reduced. For this reason, this deviation should be caused by the variation of the diffusion potential across the platinum junctions.", "contents": "[Validity of pH measurements by means of micro pH combination electrodes in blood and other biological fluids (author's transl)]. pH measurements in blood or in media containing either proteins or polypeptides and performed by means of micro pH combination electrodes type N 58 (Schott & Gen., Mainz) yield in a systematic error according to the regression line y = 1.135 chi - 0.842, in the range between pH 5.3 and 8.3. This deviation from the real pH value is independent of the protein concentration and amounts to 0.1-0.2 pH units in the  physiological range. The error does not occur if the pH measurements are performed in media which are free of proteins and polypeptides, respectively. If the electrolyte solution within the reference electrode is replaced (NaCl solution instead of KCl solution) the error is distinctly reduced. For this reason, this deviation should be caused by the variation of the diffusion potential across the platinum junctions."}
{"id": "PMID:545", "title": "The effects of drinking on offspring: an historical survey of the American and British literature.", "content": "Current research on the effects on offspring of drinking during pregnancy has revived interest in an extremely old topic. Observations made during England's Gin Epidemic (1720-1750) were followed by warnings of 19th-century medical writers that parental drinking could damage the fetus. Many concurring studies were reported in the medical literature from 1865 to 1920. Research interest declined during Prohibition, and authorities later discounted the previous work. Recently a relationship between maternal drinking and abnormal morphogenesis has been again described.", "contents": "The effects of drinking on offspring: an historical survey of the American and British literature. Current research on the effects on offspring of drinking during pregnancy has revived interest in an extremely old topic. Observations made during England's Gin Epidemic (1720-1750) were followed by warnings of 19th-century medical writers that parental drinking could damage the fetus. Many concurring studies were reported in the medical literature from 1865 to 1920. Research interest declined during Prohibition, and authorities later discounted the previous work. Recently a relationship between maternal drinking and abnormal morphogenesis has been again described."}
{"id": "PMID:543", "title": "[Glutathione (author's transl)].", "content": "Glutathione plays an important role in biology and medicine. Most cells of plants and animals contain high concentrations of reduced glutathione and a much smaller amount of oxidised glutathione. GSH is important for several metabolic functions of live cells, e.g. the protection of oxidative stress by peroxides, mediation of enzyme reactions, regulation of metabolic events, transport of amino acids across cell membranes via the gamma-glutamyl cycle, elimination of foreign compounds by GSH-conjugation, release of neurotransmitter substances. Irreversible perturbations of the glutathione metabolism may be the reason for severe clinical symptoms of hemolytic anemia or, perhaps, of central nervous disease.", "contents": "[Glutathione (author's transl)]. Glutathione plays an important role in biology and medicine. Most cells of plants and animals contain high concentrations of reduced glutathione and a much smaller amount of oxidised glutathione. GSH is important for several metabolic functions of live cells, e.g. the protection of oxidative stress by peroxides, mediation of enzyme reactions, regulation of metabolic events, transport of amino acids across cell membranes via the gamma-glutamyl cycle, elimination of foreign compounds by GSH-conjugation, release of neurotransmitter substances. Irreversible perturbations of the glutathione metabolism may be the reason for severe clinical symptoms of hemolytic anemia or, perhaps, of central nervous disease."}
{"id": "PMID:549", "title": "Hyperexcitability in the neural substrate of emotional behavior in cats after alcohol withdrawal. Evidence of a rapid development of alcohol dependence.", "content": "Substantial and prolonged withdrawal hyperexcitability in the neural substrate for affective defense was revealed by behavioral and electrophysiological measures in cats exposed to moderate to heavy doses of alcohol for periods ranging from 6 to 72 hours. The data are interpreted as indicating a rapid development of physical dependence on alcohol in this portion of the central nervous system.", "contents": "Hyperexcitability in the neural substrate of emotional behavior in cats after alcohol withdrawal. Evidence of a rapid development of alcohol dependence. Substantial and prolonged withdrawal hyperexcitability in the neural substrate for affective defense was revealed by behavioral and electrophysiological measures in cats exposed to moderate to heavy doses of alcohol for periods ranging from 6 to 72 hours. The data are interpreted as indicating a rapid development of physical dependence on alcohol in this portion of the central nervous system."}
{"id": "PMID:550", "title": "Interactions of age, sex and long-term alcohol intake in selectively bred strains of rats.", "content": "The alcohol consumption by five genotypes of rats was studied in two experiments. Alcohol intake was age-dependent in rats bred for high emotional reactivity and avoidance conditionability. Differences in consumption by sex appeared to be primarily due to differences in body weight.", "contents": "Interactions of age, sex and long-term alcohol intake in selectively bred strains of rats. The alcohol consumption by five genotypes of rats was studied in two experiments. Alcohol intake was age-dependent in rats bred for high emotional reactivity and avoidance conditionability. Differences in consumption by sex appeared to be primarily due to differences in body weight."}
{"id": "PMID:561", "title": "Regional study of acid hydrolases and lysosomal membrane properties in the normal human brain at various ages.", "content": "Acid hydrolases and lysosomal membrane properties were studied at various ages in the normal human brain. In CSF and four brain regions, the inferior olive, the cerebellar cortex, the caudate nucleus and the frontal cortex were thus beta-galactosidase, beta-glucosidase, alpha-mannosidase, hexosaminidase and acid phosphatase biochemically quantitated at ages varying between 2 and 89 years of age. Also the membrane latency for acid phosphatase was studied in these regions. No major regional quantitative differences were found with regard to the enzymes studied. Their kinetic properties were also defined. There appeared to exist a regional and intra-areal variation in lysosomal membrane permeability. There was, however, no age related increase in total enzyme contents. The possibility significance of these findings are discussed with reference to the aging process.", "contents": "Regional study of acid hydrolases and lysosomal membrane properties in the normal human brain at various ages. Acid hydrolases and lysosomal membrane properties were studied at various ages in the normal human brain. In CSF and four brain regions, the inferior olive, the cerebellar cortex, the caudate nucleus and the frontal cortex were thus beta-galactosidase, beta-glucosidase, alpha-mannosidase, hexosaminidase and acid phosphatase biochemically quantitated at ages varying between 2 and 89 years of age. Also the membrane latency for acid phosphatase was studied in these regions. No major regional quantitative differences were found with regard to the enzymes studied. Their kinetic properties were also defined. There appeared to exist a regional and intra-areal variation in lysosomal membrane permeability. There was, however, no age related increase in total enzyme contents. The possibility significance of these findings are discussed with reference to the aging process."}
{"id": "PMID:562", "title": "The late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. II. Cell-mediated immune activity.", "content": "The late effects of various immunosuppressive insults on cell-mediated immunity in mice were studied in an attempt to assess the role of immune surveillance in the aging process. Results were obtained using susceptibility to allogeneic tumor cell challenge, graft-versus-host reaction (GVHR), blastogenic response to PHA, a thymus derived T cell-specific plant mitogen, and cytolytic activity against allogeneic tumor cells as measures of immunologic activity. In vivo studies late in life show that resistance to allogeneic tumor cells is significantly decreased in thymectomized mice, whereas those treated with cortisone, cyclophosphamide and sublethal X-ray remain unchanged. Spleen cells from only the thymectomized and the sublethally irradiated mice show reduced activity in the GVHR. No difference is seen in the activity of bone marrow cells. Results consistent with these findings were obtained in in vitro studies. Thus spleen cells from thymectomized or sublethally irradiated mice show decreased activity is response to PHA, whereas no change is seen in spleen cells from other treated groups. Hence, surgical and physical insults are more likely to induce long-lasting immunosuppression in those immunocompetent tissues whose activity normally diminishes with advancing age. Furthermore, the degree of immunosuppression seen in this study is not of the order of magnitude that one could reasonably predict a significant decrease in mean life-span.", "contents": "The late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. II. Cell-mediated immune activity. The late effects of various immunosuppressive insults on cell-mediated immunity in mice were studied in an attempt to assess the role of immune surveillance in the aging process. Results were obtained using susceptibility to allogeneic tumor cell challenge, graft-versus-host reaction (GVHR), blastogenic response to PHA, a thymus derived T cell-specific plant mitogen, and cytolytic activity against allogeneic tumor cells as measures of immunologic activity. In vivo studies late in life show that resistance to allogeneic tumor cells is significantly decreased in thymectomized mice, whereas those treated with cortisone, cyclophosphamide and sublethal X-ray remain unchanged. Spleen cells from only the thymectomized and the sublethally irradiated mice show reduced activity in the GVHR. No difference is seen in the activity of bone marrow cells. Results consistent with these findings were obtained in in vitro studies. Thus spleen cells from thymectomized or sublethally irradiated mice show decreased activity is response to PHA, whereas no change is seen in spleen cells from other treated groups. Hence, surgical and physical insults are more likely to induce long-lasting immunosuppression in those immunocompetent tissues whose activity normally diminishes with advancing age. Furthermore, the degree of immunosuppression seen in this study is not of the order of magnitude that one could reasonably predict a significant decrease in mean life-span."}
{"id": "PMID:580", "title": "Lipoxygenase isozymes of peanut.", "content": "Lipoxygenase was isolated and partially purified from peanut seed by ammonium sulfate precipitation, gel filtration, and ion exchange column chromatography. Three isozymes of lipoxygenase were identified. Two had pH optima of 6.2, and the other an optimum of 8.3. Molecular weight of each isozyme was 7.3 x 10(4), as determined by gel filtration. The alkaline optimum isozyme was not inhibited by NaCN and was inhibited by CaCl2 except at very low concentrations. The acid optimum isozymes were inhibited by NaCN and were stimulated by CaCl2 concentrations up to ca. 0.7 mM.", "contents": "Lipoxygenase isozymes of peanut. Lipoxygenase was isolated and partially purified from peanut seed by ammonium sulfate precipitation, gel filtration, and ion exchange column chromatography. Three isozymes of lipoxygenase were identified. Two had pH optima of 6.2, and the other an optimum of 8.3. Molecular weight of each isozyme was 7.3 x 10(4), as determined by gel filtration. The alkaline optimum isozyme was not inhibited by NaCN and was inhibited by CaCl2 except at very low concentrations. The acid optimum isozymes were inhibited by NaCN and were stimulated by CaCl2 concentrations up to ca. 0.7 mM."}
{"id": "PMID:578", "title": "Crassin acetate, the principal antineoplastic agent in four gorgonians of the Pseudoplexaura genus.", "content": "Crassin acetate, a lactonic cembrane diterpene, has been shown to be the principal antineoplastic agent present in the marine invertebrates (gorgonians) Pseudoplexaura porosa, P. flagellosa, P. wagenaari and P. crucis.", "contents": "Crassin acetate, the principal antineoplastic agent in four gorgonians of the Pseudoplexaura genus. Crassin acetate, a lactonic cembrane diterpene, has been shown to be the principal antineoplastic agent present in the marine invertebrates (gorgonians) Pseudoplexaura porosa, P. flagellosa, P. wagenaari and P. crucis."}
{"id": "PMID:594", "title": "[Computer experience and further developments in the respiratory function laboratory (author's transl)].", "content": "Reported is on satisfactory results obtained with a small-size computer consisting of punching and scanning device, as well as plain writing machine in the respiratory function laboratory. Developed in on- as well as off-line processing by an own technical staff, a diagnostic and teaching program was established for all respiratory function routine methods with the advantages of a large number of cases examined, elimination of sources of error, considerable supply of data and information, automatic documentation and filing, plain writing, interpretation and evaluation of findings. In continuation of such works also the blood gas analysis has been included. These values as the total of disturbances of the pathophysiological acid-base status are considered and interpreted. Clinical correction is forced in this man-machine dialogue by automatic stops of the whole machinery before going on. Subsequently and in addition are computer alveolar-arterial oxygen pressure gradient, venous shunt and oxygen saturation and expressed utilizing the capacity of the small-size computer. Further developments in the respiratory function diagnostic- and teaching program for small-size computers--not too expensive in the building block principle - are intended.", "contents": "[Computer experience and further developments in the respiratory function laboratory (author's transl)]. Reported is on satisfactory results obtained with a small-size computer consisting of punching and scanning device, as well as plain writing machine in the respiratory function laboratory. Developed in on- as well as off-line processing by an own technical staff, a diagnostic and teaching program was established for all respiratory function routine methods with the advantages of a large number of cases examined, elimination of sources of error, considerable supply of data and information, automatic documentation and filing, plain writing, interpretation and evaluation of findings. In continuation of such works also the blood gas analysis has been included. These values as the total of disturbances of the pathophysiological acid-base status are considered and interpreted. Clinical correction is forced in this man-machine dialogue by automatic stops of the whole machinery before going on. Subsequently and in addition are computer alveolar-arterial oxygen pressure gradient, venous shunt and oxygen saturation and expressed utilizing the capacity of the small-size computer. Further developments in the respiratory function diagnostic- and teaching program for small-size computers--not too expensive in the building block principle - are intended."}
{"id": "PMID:609", "title": "Phosphate transport in rat liver mitochondria. Kinetics, inhibitor sensitivity, energy requirements, and labeled components.", "content": "Experiments were carried out to define the kinetic parameters of the major phosphate transport processes of rat liver mitochondria, and to obtain information about the molecular properties of these systems.", "contents": "Phosphate transport in rat liver mitochondria. Kinetics, inhibitor sensitivity, energy requirements, and labeled components. Experiments were carried out to define the kinetic parameters of the major phosphate transport processes of rat liver mitochondria, and to obtain information about the molecular properties of these systems."}
{"id": "PMID:610", "title": "L-tyrosine: 2-oxoglutarate aminotransferase induction by hydrocortisone in the thymus of the white rat.", "content": "Hydrocortisone hemisuccinate within 4 hours after in vivo administration produced an increase in precursor incoporation into rat thymus RNA and proteins in the whole animal. From these results, together with information obtained from measurements of the tyrosine aminotransferase activity and the action of mitomycin C administered one hour before the injection of hydrocortisone, it can be concluded that the increase in tissue level of the enzyme, consequent to hydrocortisone treatment, results from an increased rate of biosynthesis of the enzyme, which participates in the catabolic processes of proteins in glucocorticoid sensitive thymus cells.", "contents": "L-tyrosine: 2-oxoglutarate aminotransferase induction by hydrocortisone in the thymus of the white rat. Hydrocortisone hemisuccinate within 4 hours after in vivo administration produced an increase in precursor incoporation into rat thymus RNA and proteins in the whole animal. From these results, together with information obtained from measurements of the tyrosine aminotransferase activity and the action of mitomycin C administered one hour before the injection of hydrocortisone, it can be concluded that the increase in tissue level of the enzyme, consequent to hydrocortisone treatment, results from an increased rate of biosynthesis of the enzyme, which participates in the catabolic processes of proteins in glucocorticoid sensitive thymus cells."}
{"id": "PMID:611", "title": "Identification of the 30 S protein adjacent to peptidyl transferase catalytic center of Escherichia coli ribosomes.", "content": "Iodoacetylphenylalanyl-tRNAPhe was used as an affinity label to localize the ribosomal components involved in the peptidyl transferase catalytic center of Escherichia coli ribosomes. When labeling was carried out at pH 5.0, the affinity label could specifically label the ribosomal components which comprise the catalytic center. Analysis of ribosomal proteins which had reacted with the affinity label revealed that a 30 S subunit protein, S 20, was located at or near to the ribosomal binding site of the 3'-terminus of aminoacyl- or peptidyl-tRNA.", "contents": "Identification of the 30 S protein adjacent to peptidyl transferase catalytic center of Escherichia coli ribosomes. Iodoacetylphenylalanyl-tRNAPhe was used as an affinity label to localize the ribosomal components involved in the peptidyl transferase catalytic center of Escherichia coli ribosomes. When labeling was carried out at pH 5.0, the affinity label could specifically label the ribosomal components which comprise the catalytic center. Analysis of ribosomal proteins which had reacted with the affinity label revealed that a 30 S subunit protein, S 20, was located at or near to the ribosomal binding site of the 3'-terminus of aminoacyl- or peptidyl-tRNA."}
{"id": "PMID:616", "title": "The value of a histamine H2-receptor antagonist in the management of patients with the Zollinger-Ellison syndrome.", "content": "Inhibition of acid secretion by an H2-receptor antagonist (metiamide) was assessed in three patients with the Zollinger-Ellison syndrome. Metiamide (200 or 300 mg) inhibited acid secretion transiently (2 1/2 hours) by 85 to 100 per cent in all patients. Although anticholinergic drugs alone inhibited acid secretion by only 0 to 35 per cent in these patients, the combination of metiamide and anticholinergic markedly prolonged the inhibitory effect of metiamide. Total gastrectomy was refused by one patient, and was impossible in another; both were treated with metiamide and anticholinergic for five and 10 months. A third patient was treated with metiamide and anticholinergic for three weeks in preparation for total gastrectomy. Ulcer pain and diarrhea disappeared, and each gained weight. H2-receptor antagonists may be useful in the treatment of some patients with the Zollinger-Ellison syndrome.", "contents": "The value of a histamine H2-receptor antagonist in the management of patients with the Zollinger-Ellison syndrome. Inhibition of acid secretion by an H2-receptor antagonist (metiamide) was assessed in three patients with the Zollinger-Ellison syndrome. Metiamide (200 or 300 mg) inhibited acid secretion transiently (2 1/2 hours) by 85 to 100 per cent in all patients. Although anticholinergic drugs alone inhibited acid secretion by only 0 to 35 per cent in these patients, the combination of metiamide and anticholinergic markedly prolonged the inhibitory effect of metiamide. Total gastrectomy was refused by one patient, and was impossible in another; both were treated with metiamide and anticholinergic for five and 10 months. A third patient was treated with metiamide and anticholinergic for three weeks in preparation for total gastrectomy. Ulcer pain and diarrhea disappeared, and each gained weight. H2-receptor antagonists may be useful in the treatment of some patients with the Zollinger-Ellison syndrome."}
{"id": "PMID:626", "title": "Histamine receptors in the vasculature of the rabbit ear.", "content": "Histamine has a dual action on the isolated perfused ear preparation of the rabbit. The amine induced a dose-dependent rise in perfusion pressure when the preparation was perfused with Krebs' solution. This pressor response was reversed to a depressor effect when meypramine was added to the perfusion fluid. This depressor effect of the amine was also dose-related. Metiamide competitively inhibited the depressor effect of histamine. Prior treatment of the ear vessels with metiamide alone caused an increase in histamine-induced perfusion pressure. From these results it was concluded that the predominant pressor effect of histamine on the vascular bed of the rabbit ear is mediated through the H1-receptors and the depressor effect of the amine through histamine H2-receptors.", "contents": "Histamine receptors in the vasculature of the rabbit ear. Histamine has a dual action on the isolated perfused ear preparation of the rabbit. The amine induced a dose-dependent rise in perfusion pressure when the preparation was perfused with Krebs' solution. This pressor response was reversed to a depressor effect when meypramine was added to the perfusion fluid. This depressor effect of the amine was also dose-related. Metiamide competitively inhibited the depressor effect of histamine. Prior treatment of the ear vessels with metiamide alone caused an increase in histamine-induced perfusion pressure. From these results it was concluded that the predominant pressor effect of histamine on the vascular bed of the rabbit ear is mediated through the H1-receptors and the depressor effect of the amine through histamine H2-receptors."}
{"id": "PMID:627", "title": "Relative pre- and postsynaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery.", "content": "The rabbit pulmonary artery contains postsynaptic alpha-adrenoceptors which meidate smooth muscle contraction; its noradrenergic nerves contain presynaptic alpha-adrenoceptors which mediate inhibition of the release of the transmitter evoked by nerve impulses. Dose-response curves for the pre- and postsynaptic effects of eight alpha-receptor agonists were determined on superfused strips of the artery in the presence of cocaine, corticosterone and propranolo. 1. According to the concentrations which caused 20% of the maximal contraction (EC20 post), the postsynaptic rank order of potency was: adrenaline greater than noradrenaline greater than oxymetazoline greater than naphazoline greater than phenylephrine greater than tramazoline greater than alpha-methylnoradrenaline greater than methoxamine. The pA2 values of phentolamine againstoxymethazoline, phenylephrine, alpha-methylnoradrenaline and methoxamine were 7.43, 7.48, 7.59 and 7.69, respectively. 2. For the investigation of presynaptic effects, the arteries were preincubated with 3H-noradrenaline. All agonists inhibited the overflow of tritium evoked by transmural sympathetic nerve stimulation. According to the concentrations which reduced the stimulation-induced overflow by 20% (EC20 pre), the rank order of potency was: adrenaline greater than oxymetazoline greater than tramazoline greater than alpha-methylnoradrenaline greater than noradrenaline greater than naphazoline greater than phenylephrine greater than methoxamine. 10(-5) M phentolamine shifted the presynaptic dose-response curves for moradrenaline and oxymethazoline to the right. 3. The ratio EC20 pre/EC20 post was calculated for each agonist as an index of its relative post- and presynaptic potency. According to the ratios, the agonists were arbitrarily classified into three groups. Group 1 (ratio about 30: preferentially postsynaptic agonists) comprised methoxamine and phenylephrine; group 2 (ratio near 1; similar pre- and postsynaptic potencies) comprised noradrenaline, adrenaline and naphazoline; group 3 (ratio below 0.2; preferentially presynaptic agonists) comprised oxymetazoline, alpha-methylnoradrenaline and tramazoline (as well as clonidine). 4. Preferentially presynaptic and preferentially postsynaptic agonists had opposite effects on the basoconstrictor response to nerve stimulation. Methoxamine and phenylephrine either did not change or enhanced, but never reduced, the response. In contrast, oxymetazoline, alpha-methylnoradrenaline and tramazoline at low concentrations selectively inhibited the response to stimulation at low frequency (0.25-2Hz). 5. It is concluded that alpha-adrenoceptor agonists vary widely in their relative pre- and postsynaptic potencies, possibly because of structural differences between pre- and postsynaptic alpha-receptors. Pre- and postsynaptic components contribute to their overll postsynaptic effec in actively transmitting synapses. The preferential activation of presynaptic alpha-receptors results in alpha-adrenergic inhibition of synaptic transmission.", "contents": "Relative pre- and postsynaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery. The rabbit pulmonary artery contains postsynaptic alpha-adrenoceptors which meidate smooth muscle contraction; its noradrenergic nerves contain presynaptic alpha-adrenoceptors which mediate inhibition of the release of the transmitter evoked by nerve impulses. Dose-response curves for the pre- and postsynaptic effects of eight alpha-receptor agonists were determined on superfused strips of the artery in the presence of cocaine, corticosterone and propranolo. 1. According to the concentrations which caused 20% of the maximal contraction (EC20 post), the postsynaptic rank order of potency was: adrenaline greater than noradrenaline greater than oxymetazoline greater than naphazoline greater than phenylephrine greater than tramazoline greater than alpha-methylnoradrenaline greater than methoxamine. The pA2 values of phentolamine againstoxymethazoline, phenylephrine, alpha-methylnoradrenaline and methoxamine were 7.43, 7.48, 7.59 and 7.69, respectively. 2. For the investigation of presynaptic effects, the arteries were preincubated with 3H-noradrenaline. All agonists inhibited the overflow of tritium evoked by transmural sympathetic nerve stimulation. According to the concentrations which reduced the stimulation-induced overflow by 20% (EC20 pre), the rank order of potency was: adrenaline greater than oxymetazoline greater than tramazoline greater than alpha-methylnoradrenaline greater than noradrenaline greater than naphazoline greater than phenylephrine greater than methoxamine. 10(-5) M phentolamine shifted the presynaptic dose-response curves for moradrenaline and oxymethazoline to the right. 3. The ratio EC20 pre/EC20 post was calculated for each agonist as an index of its relative post- and presynaptic potency. According to the ratios, the agonists were arbitrarily classified into three groups. Group 1 (ratio about 30: preferentially postsynaptic agonists) comprised methoxamine and phenylephrine; group 2 (ratio near 1; similar pre- and postsynaptic potencies) comprised noradrenaline, adrenaline and naphazoline; group 3 (ratio below 0.2; preferentially presynaptic agonists) comprised oxymetazoline, alpha-methylnoradrenaline and tramazoline (as well as clonidine). 4. Preferentially presynaptic and preferentially postsynaptic agonists had opposite effects on the basoconstrictor response to nerve stimulation. Methoxamine and phenylephrine either did not change or enhanced, but never reduced, the response. In contrast, oxymetazoline, alpha-methylnoradrenaline and tramazoline at low concentrations selectively inhibited the response to stimulation at low frequency (0.25-2Hz). 5. It is concluded that alpha-adrenoceptor agonists vary widely in their relative pre- and postsynaptic potencies, possibly because of structural differences between pre- and postsynaptic alpha-receptors. Pre- and postsynaptic components contribute to their overll postsynaptic effec in actively transmitting synapses. The preferential activation of presynaptic alpha-receptors results in alpha-adrenergic inhibition of synaptic transmission."}
{"id": "PMID:628", "title": "Investigation into some imidazoline compounds, with respect to peripheral alpha-adrenoceptor stimulation and depression of cardiovascular centers.", "content": "Peripheral alpha-adrenoceptor stimulation was tested by means of hypertensive effects of the drugs following i.v. injection in spinal rats. Naphazoline (NP), oxymetazoline (OM), St 91-2-(2,6-diethylphenylimino)-2-imidazolidine--and St 1697--2-(2-ethyl, 6-methylphenylimino)-2-imidazolidine--were 3 to 5 times more potent in tthis respect thatn clonidine (CLON) whereas St 363--2-(2,4-dichlorophenylimino)-2-imidazolidine--and xylazine (XY) exerted only approx. 1/20 the effect of that of clonidine. Sympathoinhibitory activity after i.v. injection was tested by the bradycardiac effect in vagotomized rats; St 1697, St 363 and XY were active, approx. 1/10-1/30 of CLON, whereas NP, OM and St 91 were inactive. However, following intracisternal (i.ci.) injection of cardiovascular depression, typical for clonidine: (1) in dogs with blocked beta-adrenoceptors, the drugs facilitated the vagally meditated cardiodepressor reflex in response to baroreceptor stimulation by i.v. injection of angiotensin; (2) in dogs treated with atropine and in (3) vagotomized cats (only NP, OM and St 363) a long lasting decrease in heart rate was observed. Some of the experiments were complicated by increases in blood pressure, due to the \"leakage\" of small amounts of the highly vasopressor active drugs, from the cisternal spaces into the peripheral circulation. The majority of results indicated, that the central cardiovascular depressor effects of the tested drugs depend on their alpha-adrenoreceptor stimulating potency and on their ability to penetrate from cerebrospinal fluid or from the blood to cardiovascular centers. Relationships between the ability for penetration and the lipoid affinity are discussed.", "contents": "Investigation into some imidazoline compounds, with respect to peripheral alpha-adrenoceptor stimulation and depression of cardiovascular centers. Peripheral alpha-adrenoceptor stimulation was tested by means of hypertensive effects of the drugs following i.v. injection in spinal rats. Naphazoline (NP), oxymetazoline (OM), St 91-2-(2,6-diethylphenylimino)-2-imidazolidine--and St 1697--2-(2-ethyl, 6-methylphenylimino)-2-imidazolidine--were 3 to 5 times more potent in tthis respect thatn clonidine (CLON) whereas St 363--2-(2,4-dichlorophenylimino)-2-imidazolidine--and xylazine (XY) exerted only approx. 1/20 the effect of that of clonidine. Sympathoinhibitory activity after i.v. injection was tested by the bradycardiac effect in vagotomized rats; St 1697, St 363 and XY were active, approx. 1/10-1/30 of CLON, whereas NP, OM and St 91 were inactive. However, following intracisternal (i.ci.) injection of cardiovascular depression, typical for clonidine: (1) in dogs with blocked beta-adrenoceptors, the drugs facilitated the vagally meditated cardiodepressor reflex in response to baroreceptor stimulation by i.v. injection of angiotensin; (2) in dogs treated with atropine and in (3) vagotomized cats (only NP, OM and St 363) a long lasting decrease in heart rate was observed. Some of the experiments were complicated by increases in blood pressure, due to the \"leakage\" of small amounts of the highly vasopressor active drugs, from the cisternal spaces into the peripheral circulation. The majority of results indicated, that the central cardiovascular depressor effects of the tested drugs depend on their alpha-adrenoreceptor stimulating potency and on their ability to penetrate from cerebrospinal fluid or from the blood to cardiovascular centers. Relationships between the ability for penetration and the lipoid affinity are discussed."}
{"id": "PMID:629", "title": "The regulation of striatal tyrosine hydroxylase. Effects of gamma hydroxybutric acid and healperidol.", "content": "Gamma-hydroxybutyric acid (GHBA) in doses that increased the striatal dopamine (DA) content of rat brain failed to increase the affinity of striatal tyrosine hydroxylase (TH) for its pterdine cofactor or to change the sensitivity of the enzyme to the inhibition by DA. Haloperidol (1 mg/kg) decreased the apparent Km of striatal TH for the pteridine cofactor. However, when GHBA was injected before haloperidol it prevented the decrease in the apparent Kn of TH, in a dose related manner. In vitro GHBA (10(-4) M) neither changed the stimulation of the striatal adenylyl cyclase by DA nor its inhibition by haloperidol. These results suggest that in striatal dopaminergic terminals the Kn of TH for the pteridine cofactor is regulated by an molecuular mechanism which requires that the impulse flow in the DA neurons is unimpaired.", "contents": "The regulation of striatal tyrosine hydroxylase. Effects of gamma hydroxybutric acid and healperidol. Gamma-hydroxybutyric acid (GHBA) in doses that increased the striatal dopamine (DA) content of rat brain failed to increase the affinity of striatal tyrosine hydroxylase (TH) for its pterdine cofactor or to change the sensitivity of the enzyme to the inhibition by DA. Haloperidol (1 mg/kg) decreased the apparent Km of striatal TH for the pteridine cofactor. However, when GHBA was injected before haloperidol it prevented the decrease in the apparent Kn of TH, in a dose related manner. In vitro GHBA (10(-4) M) neither changed the stimulation of the striatal adenylyl cyclase by DA nor its inhibition by haloperidol. These results suggest that in striatal dopaminergic terminals the Kn of TH for the pteridine cofactor is regulated by an molecuular mechanism which requires that the impulse flow in the DA neurons is unimpaired."}
{"id": "PMID:630", "title": "Host-tumor relationship XXXIII. Inhibitor of hyaluronidase in blood serum of cancer patients.", "content": "Inhibiting activity of blood serum was determined from the decrease of N-acetyl-hexosamine end groups of hyaluronic acid products released by testicular hyaluronidase. Maximum inhibition was observed within the region of pH from 6.5 to 6.8. Correlation between the serum concentration and its inhibiting effect on hyaluronidase was found within the range of the final dilution of serum (in the reaction mixture) from 9 to 45 X. Blood sera of cancer patients showed statistically significant increase of hyaluronidase inhibitor as compared with that of health people.", "contents": "Host-tumor relationship XXXIII. Inhibitor of hyaluronidase in blood serum of cancer patients. Inhibiting activity of blood serum was determined from the decrease of N-acetyl-hexosamine end groups of hyaluronic acid products released by testicular hyaluronidase. Maximum inhibition was observed within the region of pH from 6.5 to 6.8. Correlation between the serum concentration and its inhibiting effect on hyaluronidase was found within the range of the final dilution of serum (in the reaction mixture) from 9 to 45 X. Blood sera of cancer patients showed statistically significant increase of hyaluronidase inhibitor as compared with that of health people."}
{"id": "PMID:631", "title": "Influence of peritoneal dialysis on factors affecting oxygen transport.", "content": "To determine the effect of changing concentrations of uremic metabolites on factors affecting oxygen transport, without the effects of extracorporeal blood pumping, we studied five patients before, during and after peritoneal dialysis. Significant decreases in serum urea, creatinine and phosphate and increase in serum bicarbonate were not associated with changes in P50, a reflection of hemoglobin-oxygen affinity. High erythrocyte 2,3-DPG concentrations decreased only slightly. Arterial pO2 increased slightly as negative fluid balance was achieved. The slight changes in oxygen transport parameters with dialysis suggest an interplay of compensatory factors and do not warrant modifying dialysis to limit the correction on acidosis or hyperphosphatemia. Effects on hemoglobin and pO2 resulting from fluid loss can be the dominant influence of peritoneal dialysis on tissue oxygenation.", "contents": "Influence of peritoneal dialysis on factors affecting oxygen transport. To determine the effect of changing concentrations of uremic metabolites on factors affecting oxygen transport, without the effects of extracorporeal blood pumping, we studied five patients before, during and after peritoneal dialysis. Significant decreases in serum urea, creatinine and phosphate and increase in serum bicarbonate were not associated with changes in P50, a reflection of hemoglobin-oxygen affinity. High erythrocyte 2,3-DPG concentrations decreased only slightly. Arterial pO2 increased slightly as negative fluid balance was achieved. The slight changes in oxygen transport parameters with dialysis suggest an interplay of compensatory factors and do not warrant modifying dialysis to limit the correction on acidosis or hyperphosphatemia. Effects on hemoglobin and pO2 resulting from fluid loss can be the dominant influence of peritoneal dialysis on tissue oxygenation."}
{"id": "PMID:632", "title": "Some effects of ammonium salts on renal histology and function in the dog.", "content": "NH4Cl was infused into the left renal artery of anesthetized dogs at 50-125 mum/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 mum/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO3 during arterial infusion of NH4Cl prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 mum/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis.", "contents": "Some effects of ammonium salts on renal histology and function in the dog. NH4Cl was infused into the left renal artery of anesthetized dogs at 50-125 mum/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 mum/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO3 during arterial infusion of NH4Cl prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 mum/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis."}
{"id": "PMID:633", "title": "Papillary necrosis associated with calyceal arteritis.", "content": "The renal papilla has a double blood supply - from both the vasa recta and the calyceal arteries. The importance of the latter supply is not established. A case of polyarteritis associated with papillary necrosis is reported, in which the calyceal vessels, supplying the area, show acute necrotizing arteritis and occlusion. The pathophysiological and clinical implications are discussed.", "contents": "Papillary necrosis associated with calyceal arteritis. The renal papilla has a double blood supply - from both the vasa recta and the calyceal arteries. The importance of the latter supply is not established. A case of polyarteritis associated with papillary necrosis is reported, in which the calyceal vessels, supplying the area, show acute necrotizing arteritis and occlusion. The pathophysiological and clinical implications are discussed."}
{"id": "PMID:634", "title": "Fasting uric acid and phosphate in urine and plasma of renal calcium-stone formers.", "content": "Clearance experiments in calcium-stone patients (n = 60) and controls (n = 60) demonstrated significantly higher urinary uric acid (UA) in younger (less 40 years) stone patients than controls (median: 480 vs. 351 mug/min) but not in older (greater than 40 years) patients. Serum UA and urinary oxypurines were comparable in health and stone disease. Conversely urinary phosphate was significantly lower in younger patients than matched controls (males: 224 vs. 304 mug) and presumably is responsible for the more alkaline pH. It is suggested that calcium-stone formation in humans is represented by two different populations.", "contents": "Fasting uric acid and phosphate in urine and plasma of renal calcium-stone formers. Clearance experiments in calcium-stone patients (n = 60) and controls (n = 60) demonstrated significantly higher urinary uric acid (UA) in younger (less 40 years) stone patients than controls (median: 480 vs. 351 mug/min) but not in older (greater than 40 years) patients. Serum UA and urinary oxypurines were comparable in health and stone disease. Conversely urinary phosphate was significantly lower in younger patients than matched controls (males: 224 vs. 304 mug) and presumably is responsible for the more alkaline pH. It is suggested that calcium-stone formation in humans is represented by two different populations."}
{"id": "PMID:635", "title": "Effects of varying dialysate calcium concentrations on the plasma calcium fractions in patients on dialysis.", "content": "The plasma-ionized calcium levels decreased during haemodialysis when a dialysate calcium concentration of 5 mg/100 ml was used. When dialysis was performed with a bath calcium concentration of 7.5 mg/100 ml, there was a significant increase in the plasm-ionized calcium levels in the post-dialysis period. These results are discussed in relation of the optimal dialysate calcium concentrations and development of dialytic bone disease.", "contents": "Effects of varying dialysate calcium concentrations on the plasma calcium fractions in patients on dialysis. The plasma-ionized calcium levels decreased during haemodialysis when a dialysate calcium concentration of 5 mg/100 ml was used. When dialysis was performed with a bath calcium concentration of 7.5 mg/100 ml, there was a significant increase in the plasm-ionized calcium levels in the post-dialysis period. These results are discussed in relation of the optimal dialysate calcium concentrations and development of dialytic bone disease."}
{"id": "PMID:643", "title": "[Borderline between antiepileptic and psychopharmacological drugs (author's transl)].", "content": "From the chemical and pharmalogical point of view it is impossible to separate strictly between antiepileptic and psychopharmalogical drugs. Inspite of that and several clinical overlappings it is possible and helpful finding differences between the two groups of drugs. Basing on the indication we try to demonstrate the use of these drug-groups. 1. Antiepileptic drugs in behaviour disorders. A. In spite of various publications we recommend carefullness and restriction. B. Only in case of behaviour disorders due to epileptic origin antiepileptic therapy is indicated. 2. Psychopharmalogical drugs in epilepsies A. The frequency of seizures may be reduced B. Psychical disorders connected with seizures may be influnced.", "contents": "[Borderline between antiepileptic and psychopharmacological drugs (author's transl)]. From the chemical and pharmalogical point of view it is impossible to separate strictly between antiepileptic and psychopharmalogical drugs. Inspite of that and several clinical overlappings it is possible and helpful finding differences between the two groups of drugs. Basing on the indication we try to demonstrate the use of these drug-groups. 1. Antiepileptic drugs in behaviour disorders. A. In spite of various publications we recommend carefullness and restriction. B. Only in case of behaviour disorders due to epileptic origin antiepileptic therapy is indicated. 2. Psychopharmalogical drugs in epilepsies A. The frequency of seizures may be reduced B. Psychical disorders connected with seizures may be influnced."}
{"id": "PMID:645", "title": "Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei.", "content": "Soluble glycoproteins have been purified from a series of clones of Trypanosoma brucei 427. Each clone yielded a characteristic predominant glycoprotein which induced clone-specific immunity to trypanosome infection in mice. These glycoproteins were shown by specific labelling and enzyme digestion of cells to be the major components of the trypanosome surface coat. Each glycoprotein consisted of a single polypeptide chain having an apparent molecular weight of 65 000 (as measured by SDS-polyacrylamide gel electrophoresis) and containing around 600 amino acid and 20 monosaccharide residues. Preliminary structural studies indicated large changes in amino acid sequence dispersed over a considerable length of the polypeptide chain. Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations.", "contents": "Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Soluble glycoproteins have been purified from a series of clones of Trypanosoma brucei 427. Each clone yielded a characteristic predominant glycoprotein which induced clone-specific immunity to trypanosome infection in mice. These glycoproteins were shown by specific labelling and enzyme digestion of cells to be the major components of the trypanosome surface coat. Each glycoprotein consisted of a single polypeptide chain having an apparent molecular weight of 65 000 (as measured by SDS-polyacrylamide gel electrophoresis) and containing around 600 amino acid and 20 monosaccharide residues. Preliminary structural studies indicated large changes in amino acid sequence dispersed over a considerable length of the polypeptide chain. Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations."}
{"id": "PMID:646", "title": "The determination of gamma-glutamyl transpeptidase by reaction rate assay at 37 degrees C.", "content": "The determination of gamma-glutamyl transpeptidase by a reaction rate assay using optimal reaction conditions at 37 degrees is described. Specific conditions and instrument settings are described for the LKB Reaction Rate Analyser but the actual assay conditions are applicable to any similar reaction rate system. The precision of the method has been evaluated and a reference range for normal male (less than 45 U/l) and female (less than 30 U/l) subjects determined.", "contents": "The determination of gamma-glutamyl transpeptidase by reaction rate assay at 37 degrees C. The determination of gamma-glutamyl transpeptidase by a reaction rate assay using optimal reaction conditions at 37 degrees is described. Specific conditions and instrument settings are described for the LKB Reaction Rate Analyser but the actual assay conditions are applicable to any similar reaction rate system. The precision of the method has been evaluated and a reference range for normal male (less than 45 U/l) and female (less than 30 U/l) subjects determined."}
{"id": "PMID:648", "title": "The influence of cortisol on the enzymes of fatty acid synthesis in developing mammalian lung and brain.", "content": "Administration of cortisol to fetal rabbits resulted in a 42% inhibition of pulmonary de novo fatty acid synthesis from acetyl coenzyme A (CoA) (P = less than 0.025). This was associated with inhibition of acetyl-CoA carboxylase (EC. 6.4.1.2.) activity (P = less than 0.01) and a tendency towards decreased activity of fatty acid synthetase. There was no effect on pulmonary microsomal fatty acid elongation activity. Light and electron microscopic examination of the apex of the right lung of control and cortisol-treated animals revealed changes consistent with accelerated lung maturation in the treated animals. The in vitro activities of acetyl-CoA carboxylase and fatty acid synthetase were similar in rabbit lung and thus acetyl-CoA carboxylase activity does not appear to be rate limiting for de novo fatty acid synthesis in lung. No significant change in the activity of enzymes associated with de novo fatty acid synthesis of microsomal fatty acid elongation was found in fetal brain after cortisol exposure. However, in a parallel study on fatty acid synthesis in fetal liver, cortisol administration resulted in a 30% increase in fatty acid synthetase activity (P less than 0.025). The finding of cortisol-induced inhibition of de novo fatty acid synthesis in fetal rabbit lung may be related to the known inhibitory effect of cortisol on lung growth in the fetus.", "contents": "The influence of cortisol on the enzymes of fatty acid synthesis in developing mammalian lung and brain. Administration of cortisol to fetal rabbits resulted in a 42% inhibition of pulmonary de novo fatty acid synthesis from acetyl coenzyme A (CoA) (P = less than 0.025). This was associated with inhibition of acetyl-CoA carboxylase (EC. 6.4.1.2.) activity (P = less than 0.01) and a tendency towards decreased activity of fatty acid synthetase. There was no effect on pulmonary microsomal fatty acid elongation activity. Light and electron microscopic examination of the apex of the right lung of control and cortisol-treated animals revealed changes consistent with accelerated lung maturation in the treated animals. The in vitro activities of acetyl-CoA carboxylase and fatty acid synthetase were similar in rabbit lung and thus acetyl-CoA carboxylase activity does not appear to be rate limiting for de novo fatty acid synthesis in lung. No significant change in the activity of enzymes associated with de novo fatty acid synthesis of microsomal fatty acid elongation was found in fetal brain after cortisol exposure. However, in a parallel study on fatty acid synthesis in fetal liver, cortisol administration resulted in a 30% increase in fatty acid synthetase activity (P less than 0.025). The finding of cortisol-induced inhibition of de novo fatty acid synthesis in fetal rabbit lung may be related to the known inhibitory effect of cortisol on lung growth in the fetus."}
{"id": "PMID:651", "title": "The relation between myosin adenosinetriphosphatase activity and inactivation of myosin under alkaline conditions of heart muscles in mammals of different size.", "content": "ATPase activity of myosin in the heart muscle of the mouse, rat, guinea-pig, rabbit and pig was studied at neutral pH and under mild alkaline conditions. At neutral pH the ATPase activity of myosin is inversely related to body size of the animal species. The decrease of ATPase activity of myosin after alkaline preincubation depends on the degree of ATPase activity of intact myosin, i.e. myosin from the heart of the mouse exhibits high ATPase activity ae same relationship was found, when comparing myosin of new-born and adult heart muscle. It is concluded that the rate of alkaline inactivation of heart myosin is directly related to the degree of ATPase activity of intact myosin in all animals.", "contents": "The relation between myosin adenosinetriphosphatase activity and inactivation of myosin under alkaline conditions of heart muscles in mammals of different size. ATPase activity of myosin in the heart muscle of the mouse, rat, guinea-pig, rabbit and pig was studied at neutral pH and under mild alkaline conditions. At neutral pH the ATPase activity of myosin is inversely related to body size of the animal species. The decrease of ATPase activity of myosin after alkaline preincubation depends on the degree of ATPase activity of intact myosin, i.e. myosin from the heart of the mouse exhibits high ATPase activity ae same relationship was found, when comparing myosin of new-born and adult heart muscle. It is concluded that the rate of alkaline inactivation of heart myosin is directly related to the degree of ATPase activity of intact myosin in all animals."}
{"id": "PMID:652", "title": "Carbon dioxide response curves during hypothermia.", "content": "The responsiveness of the medullary chemoreceptors, measured by the ventilatory response to hypercapnia given in an hyperoxic gas mixture in intact anesthetized dogs has been evaluated during normothermia and at two levels of hypothermia. The response was studied in: 1) 20 dogs during normothermia, 2) 10 of these dogs at a blood temperature of 32-33 degrees C, and 3) in the other 10 dogs during deeper hypothermia (28-29 degrees C). The ventilatory response to CO2 decreased while blood temperature was lowered until the response became absent during deep hypothermia. For normothermia and both levels of hypothermia a similar oxygen drive of ventilation was found which was equivalent to approximately one fourth of the spontaneous ventilation. It is suggested, that in the deeply hypothermic animal the normal respiratory drive is apparently of peripheral (arterial) chemoreceptor origin and when this drive is nullified or significantly decreased, gentle shivering could be responsible for stimulating the respiratory center.", "contents": "Carbon dioxide response curves during hypothermia. The responsiveness of the medullary chemoreceptors, measured by the ventilatory response to hypercapnia given in an hyperoxic gas mixture in intact anesthetized dogs has been evaluated during normothermia and at two levels of hypothermia. The response was studied in: 1) 20 dogs during normothermia, 2) 10 of these dogs at a blood temperature of 32-33 degrees C, and 3) in the other 10 dogs during deeper hypothermia (28-29 degrees C). The ventilatory response to CO2 decreased while blood temperature was lowered until the response became absent during deep hypothermia. For normothermia and both levels of hypothermia a similar oxygen drive of ventilation was found which was equivalent to approximately one fourth of the spontaneous ventilation. It is suggested, that in the deeply hypothermic animal the normal respiratory drive is apparently of peripheral (arterial) chemoreceptor origin and when this drive is nullified or significantly decreased, gentle shivering could be responsible for stimulating the respiratory center."}
{"id": "PMID:653", "title": "[Zollinger-Ellison syndrome treated medically by an inhibitor of H2 histamine receptors].", "content": "Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.", "contents": "[Zollinger-Ellison syndrome treated medically by an inhibitor of H2 histamine receptors]. Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations."}
{"id": "PMID:656", "title": "[Exercise test in the asthmatic patient. Study of 75 patients].", "content": "Frequency of exercise-induced asthma has been studied in 75 unselected asthmatic patients (adults and children) by measuring the forced expiratory volume at one second (FEV1) and the vital capacity (VC) before and after a treadmill exercise, continued until heart rate was at least equal to 80 p.cent-85 p.cent of maximum heart rate. In 19 subjects (25 p.cent), a more than 20 p.cent decrease from control value of FEV1 was recorded ten minutes after exercise ended. Exercise-induced bronchial obstruction was relieved by a beta adrenergic bronchodilator aerosol inhalation. In the group of 19 subjects having exercise-induced asthma, a significant positive correlation was found between pre-exercise FEV1 values and post-exercise FEV1 decreases. In the whole group of 75 subjects exercise-induced asthma was related to the severity of asthma and not to other clinical or physical characteristics of the subjects. From the data of other authors it appears that frequency of exercise-induced asthma is variable. The reasons of those differences are discussed.", "contents": "[Exercise test in the asthmatic patient. Study of 75 patients]. Frequency of exercise-induced asthma has been studied in 75 unselected asthmatic patients (adults and children) by measuring the forced expiratory volume at one second (FEV1) and the vital capacity (VC) before and after a treadmill exercise, continued until heart rate was at least equal to 80 p.cent-85 p.cent of maximum heart rate. In 19 subjects (25 p.cent), a more than 20 p.cent decrease from control value of FEV1 was recorded ten minutes after exercise ended. Exercise-induced bronchial obstruction was relieved by a beta adrenergic bronchodilator aerosol inhalation. In the group of 19 subjects having exercise-induced asthma, a significant positive correlation was found between pre-exercise FEV1 values and post-exercise FEV1 decreases. In the whole group of 75 subjects exercise-induced asthma was related to the severity of asthma and not to other clinical or physical characteristics of the subjects. From the data of other authors it appears that frequency of exercise-induced asthma is variable. The reasons of those differences are discussed."}
{"id": "PMID:657", "title": "[Anaphylactic accidents due to glaphenine. 5 cases].", "content": "The authors report 5 cases of shock type anaphylactic reactions after the ingestion of glafenine. Up to the present, acute tubulo-interstitial nephritis had chiefly been reported. The existence of allergy to this medication remains to be proved by the wider application of allergological studies.", "contents": "[Anaphylactic accidents due to glaphenine. 5 cases]. The authors report 5 cases of shock type anaphylactic reactions after the ingestion of glafenine. Up to the present, acute tubulo-interstitial nephritis had chiefly been reported. The existence of allergy to this medication remains to be proved by the wider application of allergological studies."}
{"id": "PMID:665", "title": "Intranasal betamethasone valerate in seasonal rhinitis.", "content": "A double-blind study comparing betamethasone valerate and placebo aerosols was carried out in 40 patients with a history of seasonal allergic rhinitis and positive skin tests to grass pollens. Analysis of the symptoms recorded on a daily record card for a period of one month indicated that the mean monthly symptom-score was lower for all symptoms in the group on active therapy and that this reached statistical significance for the symptom of sneezing. Significantly more antihistamine tablets were used by the placebo group as compared with the active group (p less than 0-05). The patients' assessment of their treatment was in favour of betamethasone valerate (p less than 0-05). No clinically significant side-effects were associated with the treatment, which was well tolerated.", "contents": "Intranasal betamethasone valerate in seasonal rhinitis. A double-blind study comparing betamethasone valerate and placebo aerosols was carried out in 40 patients with a history of seasonal allergic rhinitis and positive skin tests to grass pollens. Analysis of the symptoms recorded on a daily record card for a period of one month indicated that the mean monthly symptom-score was lower for all symptoms in the group on active therapy and that this reached statistical significance for the symptom of sneezing. Significantly more antihistamine tablets were used by the placebo group as compared with the active group (p less than 0-05). The patients' assessment of their treatment was in favour of betamethasone valerate (p less than 0-05). No clinically significant side-effects were associated with the treatment, which was well tolerated."}
{"id": "PMID:666", "title": "Urinary acidification in renal allografts.", "content": "Urinary acid excretion was measured in 35 human renal allograft recipients during the first few days after the onset of diuresis and two months after transplantation. In 16 out of 17 rejection episodes an early significant decrease of renal total net H+ excretion was observed. This urinary acidification impairment preceded the serum creatinine increase. Only few patients showed variations in blood pH and C1-. The acidification defect may be due to the ischaemic changes of rejection. Early impairment of urinary acidification supports a clinical diagnosis of rejection.", "contents": "Urinary acidification in renal allografts. Urinary acid excretion was measured in 35 human renal allograft recipients during the first few days after the onset of diuresis and two months after transplantation. In 16 out of 17 rejection episodes an early significant decrease of renal total net H+ excretion was observed. This urinary acidification impairment preceded the serum creatinine increase. Only few patients showed variations in blood pH and C1-. The acidification defect may be due to the ischaemic changes of rejection. Early impairment of urinary acidification supports a clinical diagnosis of rejection."}
{"id": "PMID:667", "title": "A simple test for early detection of severe renal homograft rejection.", "content": "Adding urine to a standard buffered fibrinogen solution and then coagulating it with thrombin gives reproducible coagulation times with normal urines. Coagulation of fibrinogen by thrombin is prolonged in acid solutions with a pH below six. Urines of high acidity lower the buffer pH of the fibrinogen solution below a value of six thus rendering the system uncoagulable or significantly prolonging the coagulation time. With this test system we found that out of 16 severe homograft rejections 15 were accompanied by a high acid excretion in six-hour urine specimens. Ten of these acid episodes became apparent 12 to 48 hr before clinical symptoms and before elevation of the serum creatinine could be detected.", "contents": "A simple test for early detection of severe renal homograft rejection. Adding urine to a standard buffered fibrinogen solution and then coagulating it with thrombin gives reproducible coagulation times with normal urines. Coagulation of fibrinogen by thrombin is prolonged in acid solutions with a pH below six. Urines of high acidity lower the buffer pH of the fibrinogen solution below a value of six thus rendering the system uncoagulable or significantly prolonging the coagulation time. With this test system we found that out of 16 severe homograft rejections 15 were accompanied by a high acid excretion in six-hour urine specimens. Ten of these acid episodes became apparent 12 to 48 hr before clinical symptoms and before elevation of the serum creatinine could be detected."}
{"id": "PMID:668", "title": "Catalysis by acetylcholinesterase: evidence that the rate-limiting step for acylation with certain substrates precedes general acid-base catalysis.", "content": "Inferences about the catalytic mechanism of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) are frequently made on the basis of a presumed analogy with chymotrypsin, EC 3.4.21.1. Although both enzymes are serine hydrolases, several differences in the steady-state kinetic properties of the two have been observed. In this report particular attention is focused on the second-order reaction constant, kcat/Kapp. While the reported pH dependence and deuterium oxide isotope effect associated with this parameter for chymotrypsin are generally consistent with simple models involving rate-limiting general acid-base catalysis, this study finds a more complicated situation with acetylcholinesterase. The apparent pKa of kcat/Kapp for acetylcholinesterase varies between 5.5 and 6.3 for neutral substrates and involves nonlinear inhibition by [H+]. Deuterium oxide isotope effects for kcat/Kapp range from 1.1 for acetylcholine to 1.9 for p-nitrophenyl acetate. The bimolecular reaction rate appears rate-limiting for acetylcholine at low concentrations, while a rate-limiting induced-fit step is proposed to account for apparent pKa values and low deuterium oxide isotope effects associated with low concentrations of phenyl acetate and isoamyl acetate.", "contents": "Catalysis by acetylcholinesterase: evidence that the rate-limiting step for acylation with certain substrates precedes general acid-base catalysis. Inferences about the catalytic mechanism of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) are frequently made on the basis of a presumed analogy with chymotrypsin, EC 3.4.21.1. Although both enzymes are serine hydrolases, several differences in the steady-state kinetic properties of the two have been observed. In this report particular attention is focused on the second-order reaction constant, kcat/Kapp. While the reported pH dependence and deuterium oxide isotope effect associated with this parameter for chymotrypsin are generally consistent with simple models involving rate-limiting general acid-base catalysis, this study finds a more complicated situation with acetylcholinesterase. The apparent pKa of kcat/Kapp for acetylcholinesterase varies between 5.5 and 6.3 for neutral substrates and involves nonlinear inhibition by [H+]. Deuterium oxide isotope effects for kcat/Kapp range from 1.1 for acetylcholine to 1.9 for p-nitrophenyl acetate. The bimolecular reaction rate appears rate-limiting for acetylcholine at low concentrations, while a rate-limiting induced-fit step is proposed to account for apparent pKa values and low deuterium oxide isotope effects associated with low concentrations of phenyl acetate and isoamyl acetate."}
{"id": "PMID:669", "title": "Light-dependent absorption and selective scattering changes at 518 nm in chloroplast thylakoid membranes.", "content": "The light-induced absorbance change at 518 nm of isolated chloroplasts consists of a rapid phase, and a slow phase which is complete in about 20 sec. The slow component of the 518 nm absorbance change correlates with the light-induced change in 90 degrees light scattering at 518 nm. Both show a similar time course, similar pH dependence with a maximum at pH 6.0, and similar sensitivity to inhibitors and to treatment of the chloroplasts with a low concentration of glutaraldehyde. Their light minus dark difference spectra are similar with maxima at about 520 nm. It is concluded that they are manifestations of the same phenomenon, and the slow absorbance increase at 518 nm is due to enhanced scattering. It is proposed that the light-induced changes in scattering at 518 nm reflect alterations in selective dispersion, due to proton uptake and conformational changes in the chloroplast thylakoid membrane.", "contents": "Light-dependent absorption and selective scattering changes at 518 nm in chloroplast thylakoid membranes. The light-induced absorbance change at 518 nm of isolated chloroplasts consists of a rapid phase, and a slow phase which is complete in about 20 sec. The slow component of the 518 nm absorbance change correlates with the light-induced change in 90 degrees light scattering at 518 nm. Both show a similar time course, similar pH dependence with a maximum at pH 6.0, and similar sensitivity to inhibitors and to treatment of the chloroplasts with a low concentration of glutaraldehyde. Their light minus dark difference spectra are similar with maxima at about 520 nm. It is concluded that they are manifestations of the same phenomenon, and the slow absorbance increase at 518 nm is due to enhanced scattering. It is proposed that the light-induced changes in scattering at 518 nm reflect alterations in selective dispersion, due to proton uptake and conformational changes in the chloroplast thylakoid membrane."}
{"id": "PMID:670", "title": "phiX174 DNA-dependent DNA synthesis in vitro: requirement for P1 ban protein in dnaB mutant extracts of Escherichia coli.", "content": "Ammonium sulfate fractionation of crude extracts of E. coli yields a soluble enzyme fraction (about 25-fold purification) that catalyzes the conversion of phiX174 single-stranded DNA to duplex DNA. The reaction is rifampicin-resistant, requires single-stranded DNA, Mg++, deoxynucleoside triphosphates, and ATP, and is stimulated by KCl. Such soluble enzyme fractions were prepared from E. coli strains carrying the prophage mutant P1bac, in which the viral dnaB analog (ban) protein is expressed constitutively, or P1bacban, in which the expression of ban protein is prevented. DNA-synthesizing activity of ban protein containing fractions from wild-type or dnaB(P1bac) lysogens was more temperature-resistant than that from E. coli containing only wild-type dnaB protein, whereas that from dnaB(P1bacban) lysogens of dnaB cells was extremely thermolabile. It is suggested that the temperature-resistant DNA synthesis with fractions from P1bac lysogens is mediated by the P1 ban protein.", "contents": "phiX174 DNA-dependent DNA synthesis in vitro: requirement for P1 ban protein in dnaB mutant extracts of Escherichia coli. Ammonium sulfate fractionation of crude extracts of E. coli yields a soluble enzyme fraction (about 25-fold purification) that catalyzes the conversion of phiX174 single-stranded DNA to duplex DNA. The reaction is rifampicin-resistant, requires single-stranded DNA, Mg++, deoxynucleoside triphosphates, and ATP, and is stimulated by KCl. Such soluble enzyme fractions were prepared from E. coli strains carrying the prophage mutant P1bac, in which the viral dnaB analog (ban) protein is expressed constitutively, or P1bacban, in which the expression of ban protein is prevented. DNA-synthesizing activity of ban protein containing fractions from wild-type or dnaB(P1bac) lysogens was more temperature-resistant than that from E. coli containing only wild-type dnaB protein, whereas that from dnaB(P1bacban) lysogens of dnaB cells was extremely thermolabile. It is suggested that the temperature-resistant DNA synthesis with fractions from P1bac lysogens is mediated by the P1 ban protein."}
{"id": "PMID:671", "title": "Intramolecular arsanilazotyrosine-248-Zn complex of carboxypeptidase A: a monitor of catalytic events.", "content": "The intensely chromophoric intramolecular coordination complex formed between arsanilazotyrosine-248 and the active site zinc atom of azocarboxypeptidase A (Johansen, J. T. & Vallee, B. L. (1971) Proc. Nat. Acad. Sci. USA 68, 2532-2535) is a spectrokinetic probe of catalytic events. The interconversion of the azoTyr-248-Zn complex and its constituents is measured by stopped-flow pH and temperature-jump methods. The rate of interconversion, 64,000 sec-1, is orders of magnitude faster than that of the catalytic step itself (about 0.01-100 sec-1). Rapidly turned over peptide and ester substrates disrupt the azoTyr-248-Zn complex before hydrolysis occurs. As a consequence, formation of azoTyr-248, substrate binding, and catalysis can all be monitored while catalysis is actually in progress. The results of these dynamic studies specify a course of catalytic events, different from those postulated based on x-ray structure analysis. If azoTyr-248 is displaced, the direction is opposite to the inward movement postulated on the basis of x-ray studies and is not unique to induction by substrates, since rapid changes in pH also result in analogous spectral changes. AzoTyr-248 carboxypeptidase has all the features which are essential for mechanistic studies: (1) It is enzymatically active; (2) the spectra of the metal complex differ characteristically from those of its constituents; (3) it responds dynamically to environmental factors; and (4) the response time of the probe itself is much more rapid than is required for the measurement of the catalytic step. These combined kinetic and spectral properties of the metal complex render it a powerful spectrokinetic probe to visualize and discern microscopic details of the catalytic process.", "contents": "Intramolecular arsanilazotyrosine-248-Zn complex of carboxypeptidase A: a monitor of catalytic events. The intensely chromophoric intramolecular coordination complex formed between arsanilazotyrosine-248 and the active site zinc atom of azocarboxypeptidase A (Johansen, J. T. & Vallee, B. L. (1971) Proc. Nat. Acad. Sci. USA 68, 2532-2535) is a spectrokinetic probe of catalytic events. The interconversion of the azoTyr-248-Zn complex and its constituents is measured by stopped-flow pH and temperature-jump methods. The rate of interconversion, 64,000 sec-1, is orders of magnitude faster than that of the catalytic step itself (about 0.01-100 sec-1). Rapidly turned over peptide and ester substrates disrupt the azoTyr-248-Zn complex before hydrolysis occurs. As a consequence, formation of azoTyr-248, substrate binding, and catalysis can all be monitored while catalysis is actually in progress. The results of these dynamic studies specify a course of catalytic events, different from those postulated based on x-ray structure analysis. If azoTyr-248 is displaced, the direction is opposite to the inward movement postulated on the basis of x-ray studies and is not unique to induction by substrates, since rapid changes in pH also result in analogous spectral changes. AzoTyr-248 carboxypeptidase has all the features which are essential for mechanistic studies: (1) It is enzymatically active; (2) the spectra of the metal complex differ characteristically from those of its constituents; (3) it responds dynamically to environmental factors; and (4) the response time of the probe itself is much more rapid than is required for the measurement of the catalytic step. These combined kinetic and spectral properties of the metal complex render it a powerful spectrokinetic probe to visualize and discern microscopic details of the catalytic process."}
{"id": "PMID:672", "title": "Ubiquinone-mediated coupling of NADH dehydrogenase to active transport in membrane vesicles from Escherichia coli.", "content": "Addition of ubiquinone-1 to E. coli ML 308-225 membrane vesicles dramatically increases coupling between NADH oxidation and active transport such that initial rates and steady-state levels of lactose and amino-acid accumulation are comparable to those observed during D-lactate oxidation. Similar but less dramatic effects are observed with the quinone and succinate or L-lactate. In the presence of NADH and ubiquinone-1, the vesicles also generate a membrane potential (interior negative) that is similar in magnitude to that observed in the presence of D-lactate. Stimulation of NADH-dependent transport by ubiquinone-1 cannot be accounted for by increased rates of oxidation of NADH, and the effect of the quinone on NADH-dependent lactose transport is not observed in vesicles depleted of NADH dehydrogenase activity. Thus, it is apparent that ubiquinone-1 shunts electrons from NADH dehydrogenase [NADH:(acceptor)oxidoreductase; EC 1.6.99.3] to the portion of the respiratory chain containing the energy-coupling site. The findings demonstrate unequivocally that inefficient coupling of NADH oxidation to active transport cannot be due to the presence of inverted vesicles. In addition, they provide further support for specific localization of the energy-coupling site.", "contents": "Ubiquinone-mediated coupling of NADH dehydrogenase to active transport in membrane vesicles from Escherichia coli. Addition of ubiquinone-1 to E. coli ML 308-225 membrane vesicles dramatically increases coupling between NADH oxidation and active transport such that initial rates and steady-state levels of lactose and amino-acid accumulation are comparable to those observed during D-lactate oxidation. Similar but less dramatic effects are observed with the quinone and succinate or L-lactate. In the presence of NADH and ubiquinone-1, the vesicles also generate a membrane potential (interior negative) that is similar in magnitude to that observed in the presence of D-lactate. Stimulation of NADH-dependent transport by ubiquinone-1 cannot be accounted for by increased rates of oxidation of NADH, and the effect of the quinone on NADH-dependent lactose transport is not observed in vesicles depleted of NADH dehydrogenase activity. Thus, it is apparent that ubiquinone-1 shunts electrons from NADH dehydrogenase [NADH:(acceptor)oxidoreductase; EC 1.6.99.3] to the portion of the respiratory chain containing the energy-coupling site. The findings demonstrate unequivocally that inefficient coupling of NADH oxidation to active transport cannot be due to the presence of inverted vesicles. In addition, they provide further support for specific localization of the energy-coupling site."}
{"id": "PMID:673", "title": "Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution.", "content": "After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection. These observations contribute to understanding of some of the persisting immunodeficiencies that are observed in man after fatal irradiation and bone marrow transplantation. These results should suggest better approaches to more effective cellular engineering for correction of immunodeficiency diseases and for treatment of immunodeficiency diseases and of leukemias and malignancies of man.", "contents": "Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution. After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection. These observations contribute to understanding of some of the persisting immunodeficiencies that are observed in man after fatal irradiation and bone marrow transplantation. These results should suggest better approaches to more effective cellular engineering for correction of immunodeficiency diseases and for treatment of immunodeficiency diseases and of leukemias and malignancies of man."}
{"id": "PMID:674", "title": "Mechanism of action of penicillin: triggering of the pneumococcal autolytic enzyme by inhibitors of cell wall synthesis.", "content": "During penicillin treatment of an autolysin defective mutant pneumococcus we have observed three novel phenomena: (i) Growth of the mutant cultures is inhibited by the same concentrations of penicillin that induce lysis in the wild type. (ii) Mutant bacteria treated with the minimum growth inhibitory concentration of penicillin will lyse upon the addition of wild-type autolysin to the growth medium. Chloramphenicol and other inhibitors of protein synthesis protect the cells against lysis by exogenous enzyme. Sensitivity of the cells to exogenous autolysin requires treatment with penicillin or other inhibitors of cell wall synthesis (e.g., D-cycloserine or fosfonomycin) since exogenous autolysin alone has no effect on bacterial growth. (iii) Treatment with penicillin (or other inhibitors of cell wall synthesis) causes the escape into the medium of a choline-containing macromolecule that has properties suggesting that it contains pneumococcal lipoteichoic acid (Forssman antigen). Each one of these three phenomena (growth inhibition, sensitization to exogenous autolysin, and leakage of lipoteichoic acid) shows the same dose response as that of the penicillin-induced lysis of wild-type pneumococci. On the basis of these findings we propose a new hypothesis for the mechanism of penicillin-induced lysis of bacteria. It is suggested that inhibition of cell wall synthesis by any means triggers bacterial autolytic enzymes by destabilizing the endogenous complex of an autolysin inhibitor (lipoteichoic acid) and autolytic enzyme. Escape of lipoteichoic acid-like material to the growth medium is a consequence of this labilization. Chloramphenicol protects bacteria against penicillin-induced lysis by interfering with the activity of the autolytic enzyme, rather than by depleting the concentration of the enzyme at the cell surface.", "contents": "Mechanism of action of penicillin: triggering of the pneumococcal autolytic enzyme by inhibitors of cell wall synthesis. During penicillin treatment of an autolysin defective mutant pneumococcus we have observed three novel phenomena: (i) Growth of the mutant cultures is inhibited by the same concentrations of penicillin that induce lysis in the wild type. (ii) Mutant bacteria treated with the minimum growth inhibitory concentration of penicillin will lyse upon the addition of wild-type autolysin to the growth medium. Chloramphenicol and other inhibitors of protein synthesis protect the cells against lysis by exogenous enzyme. Sensitivity of the cells to exogenous autolysin requires treatment with penicillin or other inhibitors of cell wall synthesis (e.g., D-cycloserine or fosfonomycin) since exogenous autolysin alone has no effect on bacterial growth. (iii) Treatment with penicillin (or other inhibitors of cell wall synthesis) causes the escape into the medium of a choline-containing macromolecule that has properties suggesting that it contains pneumococcal lipoteichoic acid (Forssman antigen). Each one of these three phenomena (growth inhibition, sensitization to exogenous autolysin, and leakage of lipoteichoic acid) shows the same dose response as that of the penicillin-induced lysis of wild-type pneumococci. On the basis of these findings we propose a new hypothesis for the mechanism of penicillin-induced lysis of bacteria. It is suggested that inhibition of cell wall synthesis by any means triggers bacterial autolytic enzymes by destabilizing the endogenous complex of an autolysin inhibitor (lipoteichoic acid) and autolytic enzyme. Escape of lipoteichoic acid-like material to the growth medium is a consequence of this labilization. Chloramphenicol protects bacteria against penicillin-induced lysis by interfering with the activity of the autolytic enzyme, rather than by depleting the concentration of the enzyme at the cell surface."}
{"id": "PMID:675", "title": "Identification of NADPH-thioredoxin reductase system in Euglena gracillis.", "content": "Euglena gracilis contains a protein system which can utilize the reducing power of NADPH in the ribonucleotide reductase-catalyzed reduction of CTP. The proteins required for this reaction are a flavoprotien with a molecular weight of approximately 185,000 which is functionally similar to thioredoxin reductase (NADPH), EC 1.6.4.5, and another protein (Protein I) whose function in the reaction is unknown. This new protein does not appear to contain a prosthetic group and has a molecular weight of approximately 240,000. In addition, the ribonucleotide reductase active in the Euglena NADPH-thioredoxin reductase system is more complex than the protein reported in a previous publication [(1974) j. Biol. Chem. 249, 4428-4434]. The enzyme preparation described in this report contains four different types of polypeptide chains which may complex to form the active enzyme.", "contents": "Identification of NADPH-thioredoxin reductase system in Euglena gracillis. Euglena gracilis contains a protein system which can utilize the reducing power of NADPH in the ribonucleotide reductase-catalyzed reduction of CTP. The proteins required for this reaction are a flavoprotien with a molecular weight of approximately 185,000 which is functionally similar to thioredoxin reductase (NADPH), EC 1.6.4.5, and another protein (Protein I) whose function in the reaction is unknown. This new protein does not appear to contain a prosthetic group and has a molecular weight of approximately 240,000. In addition, the ribonucleotide reductase active in the Euglena NADPH-thioredoxin reductase system is more complex than the protein reported in a previous publication [(1974) j. Biol. Chem. 249, 4428-4434]. The enzyme preparation described in this report contains four different types of polypeptide chains which may complex to form the active enzyme."}
{"id": "PMID:676", "title": "Purification of folate binding factor in normal umbilical cord serum.", "content": "Human umbilical cord serum was found to contain both free folate and folate complexed to a high-molecular weight factor. The complexed folate was bound to a very high affinity binder and was present in concentrations equivalent to as much as 60 ng of 5-methyltetrahydrofolic acid per ml of serum. Acidification of the serum caused disassociation of the folate-binder complex. Released folates were separated from binder by Sephadex gel filtration, zonal centrifugation through sucrose gradients, or adsorption onto activated charcoal. The separated binding factor, either saturated or unsaturated with folate, had a molecular weight of about 40,000 on Sephadex G-200 chromatography. Binding of [3H]pteroylglutamic acid was rapid and, as in the original endogenous folate-binder complex, was essentially irreversible at neutral pH. The affinity and specificity of the binder were examined by competition experiments using [3H]pteroylglutamic acid and nonradioactive folate derivatives. Oxidized folates were bound in preference to reduced derivatives, but only three to four times more unlabeled 5-methyltetrahydrofolic acid than pteroylglutamic acid was required to produce an equal level of competition. The strong affinity for 5-methyltetrahydrofolic acid, the main serum folate, suggests that the binder could be part of the mechanism by which the fetus concentrates maternally supplied folate for its growth and development.", "contents": "Purification of folate binding factor in normal umbilical cord serum. Human umbilical cord serum was found to contain both free folate and folate complexed to a high-molecular weight factor. The complexed folate was bound to a very high affinity binder and was present in concentrations equivalent to as much as 60 ng of 5-methyltetrahydrofolic acid per ml of serum. Acidification of the serum caused disassociation of the folate-binder complex. Released folates were separated from binder by Sephadex gel filtration, zonal centrifugation through sucrose gradients, or adsorption onto activated charcoal. The separated binding factor, either saturated or unsaturated with folate, had a molecular weight of about 40,000 on Sephadex G-200 chromatography. Binding of [3H]pteroylglutamic acid was rapid and, as in the original endogenous folate-binder complex, was essentially irreversible at neutral pH. The affinity and specificity of the binder were examined by competition experiments using [3H]pteroylglutamic acid and nonradioactive folate derivatives. Oxidized folates were bound in preference to reduced derivatives, but only three to four times more unlabeled 5-methyltetrahydrofolic acid than pteroylglutamic acid was required to produce an equal level of competition. The strong affinity for 5-methyltetrahydrofolic acid, the main serum folate, suggests that the binder could be part of the mechanism by which the fetus concentrates maternally supplied folate for its growth and development."}
{"id": "PMID:677", "title": "Intramolecular arsanilazotyrosine-248-Zn complex of carboxypeptidase A: a monitor of multiple conformational states in solution.", "content": "The red azoTyr-248-Zn complex of arnilazocarboxypeptidase, previously used to demonstrate differences in conformation of the enzyme in crystals and in solution, has now provided means to detect multiple conformations of the enzyme in solution by stopped-flow pH and temperature jump experiments. These studies identify two distinct processes. Er + H+ in equilibrium Ey (I), is the extremely rapid, Kfast about 10(5) sec-1, pH dependent dissociation of the metal complex. Ey in equilibrium Ey' (II), is much slower, Kslow about 5 sec-1, pH independent interconversion of two distinct populations of protein molecules, Ey and Ey', in which the yellow azo-Tyr-248 is different conformations. These two conformations can be differentiated readily by stopped-flow pH-jump experiments, since I is three to four orders of magnitude faster than II. Mathematical expressions derived from this mechanism accurately predict all observations over the pH range from 6.0 to 8.5. In a previous stopped-flow pH-jump experiment, Lipcomb and coworkers [Quiocho, F. A., McMurray, C. H. & Lipcomb, W. H. (1972), Proc. Nat. Acad. Sci. USA 69, 2850-2854] recognized only a single process with a rate constant of about 6 sec-1, but not the major, very rapid rate observed here. The failure to detect this fast process led to the postulation of a number of explanations intended to account for the detection of only a single, slow rate. The present observations show that the premise for those conjectures is not valid. The azoprobe reveals the existence of rapidly interconvertible substructures of carboxypeptidase A, and the results support the view that in solution, enzymes can adopt multiple, readily interconvertible and related conformations which could then either facilitate or impede catalysis. In crystals, rearrangement of molecular structure could be severely impaired or restricted, and crystallization might single out either active or inactive conformations. In the latter case, such crystals would have greatly reduced activities and markedly altered catalytic behavior, as is observed for carboxypeptidase A. In combination with detailed kinetic analysis of crystals, conformational analysis in solution should be a valuable guide to discern enzyme mechanisms and select crystals for x-ray structure analysis.", "contents": "Intramolecular arsanilazotyrosine-248-Zn complex of carboxypeptidase A: a monitor of multiple conformational states in solution. The red azoTyr-248-Zn complex of arnilazocarboxypeptidase, previously used to demonstrate differences in conformation of the enzyme in crystals and in solution, has now provided means to detect multiple conformations of the enzyme in solution by stopped-flow pH and temperature jump experiments. These studies identify two distinct processes. Er + H+ in equilibrium Ey (I), is the extremely rapid, Kfast about 10(5) sec-1, pH dependent dissociation of the metal complex. Ey in equilibrium Ey' (II), is much slower, Kslow about 5 sec-1, pH independent interconversion of two distinct populations of protein molecules, Ey and Ey', in which the yellow azo-Tyr-248 is different conformations. These two conformations can be differentiated readily by stopped-flow pH-jump experiments, since I is three to four orders of magnitude faster than II. Mathematical expressions derived from this mechanism accurately predict all observations over the pH range from 6.0 to 8.5. In a previous stopped-flow pH-jump experiment, Lipcomb and coworkers [Quiocho, F. A., McMurray, C. H. & Lipcomb, W. H. (1972), Proc. Nat. Acad. Sci. USA 69, 2850-2854] recognized only a single process with a rate constant of about 6 sec-1, but not the major, very rapid rate observed here. The failure to detect this fast process led to the postulation of a number of explanations intended to account for the detection of only a single, slow rate. The present observations show that the premise for those conjectures is not valid. The azoprobe reveals the existence of rapidly interconvertible substructures of carboxypeptidase A, and the results support the view that in solution, enzymes can adopt multiple, readily interconvertible and related conformations which could then either facilitate or impede catalysis. In crystals, rearrangement of molecular structure could be severely impaired or restricted, and crystallization might single out either active or inactive conformations. In the latter case, such crystals would have greatly reduced activities and markedly altered catalytic behavior, as is observed for carboxypeptidase A. In combination with detailed kinetic analysis of crystals, conformational analysis in solution should be a valuable guide to discern enzyme mechanisms and select crystals for x-ray structure analysis."}
{"id": "PMID:678", "title": "Presence of norepinephrine and related enzymes in isolated brain microvessels.", "content": "Norepinephrine and the enzymes involved in its synthesis and degradation were found to be associated with isolated brain microvessels. The significance of these results are discussed with respect to adrenergic innervation of the cerebral microvessels and thereby neural regulation of the cerebral microcirculation.", "contents": "Presence of norepinephrine and related enzymes in isolated brain microvessels. Norepinephrine and the enzymes involved in its synthesis and degradation were found to be associated with isolated brain microvessels. The significance of these results are discussed with respect to adrenergic innervation of the cerebral microvessels and thereby neural regulation of the cerebral microcirculation."}
{"id": "PMID:681", "title": "Disorders of micturition in bacterial prostatitis.", "content": "Measurements of urinary flow rate were performed in 16 patients with established prostatitis before and after a course of antimicrobial therapy. Before treatment the maximum flow rates were poor with abnormal flow curves and significant improvement in voiding characteristics were observed with treatment (P less than 0.01). A preliminary electrophysiological (EMG) study of sphincter activity suggested that the obstruction to the flow of urine was at least in part due to failure of the external sphincter to relax during micturition. Although the total number of cases in this series was small the study showed that prostatitis was associated with a disorder of micturition which correlated with the other clinical features of the disease and could be objectively evaluated. Eradication of infection restored normal conditions in the lower urinary tract.", "contents": "Disorders of micturition in bacterial prostatitis. Measurements of urinary flow rate were performed in 16 patients with established prostatitis before and after a course of antimicrobial therapy. Before treatment the maximum flow rates were poor with abnormal flow curves and significant improvement in voiding characteristics were observed with treatment (P less than 0.01). A preliminary electrophysiological (EMG) study of sphincter activity suggested that the obstruction to the flow of urine was at least in part due to failure of the external sphincter to relax during micturition. Although the total number of cases in this series was small the study showed that prostatitis was associated with a disorder of micturition which correlated with the other clinical features of the disease and could be objectively evaluated. Eradication of infection restored normal conditions in the lower urinary tract."}
{"id": "PMID:698", "title": "Nonenzymatic reactivation of des-acetyl citrate lyase by acetyl adenylate. First example of enzyme activation by chemotrophic modification.", "content": "The experimental conditions of nonenzymatic reactivation of des-acetyl citrate lyase from K. aerogenes were studied. It was found that at pH 8.5 0.2 MM acetyl AMP causes a fast reactivation of the enzyme. The pH dependence of activity and the Km for citrate are very similar for both native and reactivated enzyme.", "contents": "Nonenzymatic reactivation of des-acetyl citrate lyase by acetyl adenylate. First example of enzyme activation by chemotrophic modification. The experimental conditions of nonenzymatic reactivation of des-acetyl citrate lyase from K. aerogenes were studied. It was found that at pH 8.5 0.2 MM acetyl AMP causes a fast reactivation of the enzyme. The pH dependence of activity and the Km for citrate are very similar for both native and reactivated enzyme."}
{"id": "PMID:699", "title": "Relationship between bovine serum albumin structure and its chemical equilibria with hydrogen and 5-hydroxytryptamine ions.", "content": "From the analysis of titration curves with hydrogen and 5-HT ions, it was found that the electrostatic interaction parameter of protein macroion and the number sites of 5-HT fixing were smaller over an acid and base pH range as compared to their values at neutral pH. Our data were interpreted by the conformational changes which can be induced when BSA is exposed to denaturation by acid and alkali pH.", "contents": "Relationship between bovine serum albumin structure and its chemical equilibria with hydrogen and 5-hydroxytryptamine ions. From the analysis of titration curves with hydrogen and 5-HT ions, it was found that the electrostatic interaction parameter of protein macroion and the number sites of 5-HT fixing were smaller over an acid and base pH range as compared to their values at neutral pH. Our data were interpreted by the conformational changes which can be induced when BSA is exposed to denaturation by acid and alkali pH."}
{"id": "PMID:701", "title": "Some psysicochemical properties of mitochondrial and cell sap alanine aminotransferase from the rat CNS.", "content": "The authors describe different properties of brain mitochondrial and cell sap alanine aminotransferase. They showed that the mitochondrial enzyme was inhibited by maleate, chlorides, acetate and phosphate with a high ionic strength (over 1.8), that its pH optimum lay between 7.5 and 8.5, that it was thermolabile at over 40 degrees C and that it was salted out from solutions with ammonium sulphate at 0.6--0.8 saturation. The activity of the cell sap enzyme was inhibited by phosphate at an ionic strength of only 0.12, less markedly by maleate and not at all by chlorides and acetate; its pH optimum was about 8, it was thermostable up to 60 degrees C and was precipitated from ammonium sulphate solution at between 0.35 and 0.6 saturation. The authors conclude from their results that two different alanine aminotransferase enzymes are present in the CNS.", "contents": "Some psysicochemical properties of mitochondrial and cell sap alanine aminotransferase from the rat CNS. The authors describe different properties of brain mitochondrial and cell sap alanine aminotransferase. They showed that the mitochondrial enzyme was inhibited by maleate, chlorides, acetate and phosphate with a high ionic strength (over 1.8), that its pH optimum lay between 7.5 and 8.5, that it was thermolabile at over 40 degrees C and that it was salted out from solutions with ammonium sulphate at 0.6--0.8 saturation. The activity of the cell sap enzyme was inhibited by phosphate at an ionic strength of only 0.12, less markedly by maleate and not at all by chlorides and acetate; its pH optimum was about 8, it was thermostable up to 60 degrees C and was precipitated from ammonium sulphate solution at between 0.35 and 0.6 saturation. The authors conclude from their results that two different alanine aminotransferase enzymes are present in the CNS."}
{"id": "PMID:702", "title": "[Postvacccinal encephalomyelitis after protective antirabic innoculation, combined with polioencephalomyelitis (lyssa?)].", "content": "By means of two cases of postvaccinal encephalomyelitis following antirabies vaccination has been demonstrated the meaning of these complications. In one of these cases has been presumed a simultaneous illness of quiet rabies. The difficulty of an aetiological diagnostic by the morphological effigy of the encephalomyelitids has been referred. An improvement of the dispensaire-system and of the diagnostic of complications following antirabies vaccination is postulated.", "contents": "[Postvacccinal encephalomyelitis after protective antirabic innoculation, combined with polioencephalomyelitis (lyssa?)]. By means of two cases of postvaccinal encephalomyelitis following antirabies vaccination has been demonstrated the meaning of these complications. In one of these cases has been presumed a simultaneous illness of quiet rabies. The difficulty of an aetiological diagnostic by the morphological effigy of the encephalomyelitids has been referred. An improvement of the dispensaire-system and of the diagnostic of complications following antirabies vaccination is postulated."}
{"id": "PMID:706", "title": "The effect of L-dopa on young patients with simple schizophrenia, treated with neuroleptic drugs: a double-blind cross-over trial with Madopar and placebo.", "content": "Thirteen out of 18 young out-patients with simple schizophrenia under neuroleptic treatment completed a double-blind cross-over trial with Madopar [L-Dopa + benserazid (a peripheral decarboxylase inhibitor)] and placebo. Nine patients were given 900 mg L-Dopa + 225 mg benserazid daily, 1 patient received 600 mg L-Dopa + 150 mg benserazid, and 3 patients, 300 mg L-Dopa + 75 mg benserazid. In these doses, L-Dopa was effective against emotional withdrawal, blunted affect, tendency to isolation and apathy, without inducing or aggravating productive, accessory symptoms. The activity score, according to the specific activity-withdrawal scale, was significantly increased (P less than 0.05), whereas the total BPRS score (Brief Psychiatric Rating Scale) was slightly, but significantly reduced (P less than 0.05). In cases where L-Dopa had to be limited to 600 and 300 mg daily, a tendency to anxiety, distortion of thinking, and a sense of unreality were observed, depending on the dose of L-Dopa. In no case were gastrointestinal, cardiovascular or neurological side-effects observed.", "contents": "The effect of L-dopa on young patients with simple schizophrenia, treated with neuroleptic drugs: a double-blind cross-over trial with Madopar and placebo. Thirteen out of 18 young out-patients with simple schizophrenia under neuroleptic treatment completed a double-blind cross-over trial with Madopar [L-Dopa + benserazid (a peripheral decarboxylase inhibitor)] and placebo. Nine patients were given 900 mg L-Dopa + 225 mg benserazid daily, 1 patient received 600 mg L-Dopa + 150 mg benserazid, and 3 patients, 300 mg L-Dopa + 75 mg benserazid. In these doses, L-Dopa was effective against emotional withdrawal, blunted affect, tendency to isolation and apathy, without inducing or aggravating productive, accessory symptoms. The activity score, according to the specific activity-withdrawal scale, was significantly increased (P less than 0.05), whereas the total BPRS score (Brief Psychiatric Rating Scale) was slightly, but significantly reduced (P less than 0.05). In cases where L-Dopa had to be limited to 600 and 300 mg daily, a tendency to anxiety, distortion of thinking, and a sense of unreality were observed, depending on the dose of L-Dopa. In no case were gastrointestinal, cardiovascular or neurological side-effects observed."}
{"id": "PMID:707", "title": "The specificity of binding of the narcotic agonist etorphine in synaptic membranes of rat brain in vivo.", "content": "When 3H-etorphine was administered to rats in a pharmacologically effective dose (0.75 mug/kg intracisternally), the labeled drug was concentrated in synaptic membrane fractions isolated from the brains of rats killed 10 min after etorphine injection. Pretreatment of the animals with the narcotic antagonists naloxone, diprenorphine or l-cyclorphan, blocked the pharmacological responses to etorphine and reduced 3H-etorphine binding in the membrane fractions. The differences between 3H-etorphine bound in synaptic membranes of rats treated with d-cyclorphan (inactive isomer) and l-cyclorphan (active antagonist) were in the same range as the reductions in etorphine binding in antagonist-treated rats, indicating that stereospecific and pharmacologically-specific binding sites in synaptic membranes in vivo were of the same magnitude: about 0.04 pmol/g brain.", "contents": "The specificity of binding of the narcotic agonist etorphine in synaptic membranes of rat brain in vivo. When 3H-etorphine was administered to rats in a pharmacologically effective dose (0.75 mug/kg intracisternally), the labeled drug was concentrated in synaptic membrane fractions isolated from the brains of rats killed 10 min after etorphine injection. Pretreatment of the animals with the narcotic antagonists naloxone, diprenorphine or l-cyclorphan, blocked the pharmacological responses to etorphine and reduced 3H-etorphine binding in the membrane fractions. The differences between 3H-etorphine bound in synaptic membranes of rats treated with d-cyclorphan (inactive isomer) and l-cyclorphan (active antagonist) were in the same range as the reductions in etorphine binding in antagonist-treated rats, indicating that stereospecific and pharmacologically-specific binding sites in synaptic membranes in vivo were of the same magnitude: about 0.04 pmol/g brain."}
{"id": "PMID:708", "title": "The cholinergic system and nociception in the primate: interactions with morphine.", "content": "In Experiment 1 the shock titration task was used to evaluate the antinoceptive properties of 5 different classes of cholinergic compounds in the rhesus monkey. Only scopolamine and high doses of physostigmine were effective in elevating the shock threshold. The apparent antinociceptive effect of physostigmine, however, was difficult to separate from its nonspecific behavioral depressant effect and was probably not related to an increase in cholinergic tone. Experiment 2 examined the interaction of morphine with arecoline, scopolamine and physostigmine. Only scopolamine (0.05 and 0.1 mg/kg) and high doses of physostigmine (0.1 mg/kg) interacted with morphine in the shock titration paradigm. The multiplicative interaction of morphine with scopolamine was confirmed in Experiment 3 over a wider range of doses. It was concluded that morphine and the cholinergic compounds produce antinociceptive effects through different mechanisms of the pain system.", "contents": "The cholinergic system and nociception in the primate: interactions with morphine. In Experiment 1 the shock titration task was used to evaluate the antinoceptive properties of 5 different classes of cholinergic compounds in the rhesus monkey. Only scopolamine and high doses of physostigmine were effective in elevating the shock threshold. The apparent antinociceptive effect of physostigmine, however, was difficult to separate from its nonspecific behavioral depressant effect and was probably not related to an increase in cholinergic tone. Experiment 2 examined the interaction of morphine with arecoline, scopolamine and physostigmine. Only scopolamine (0.05 and 0.1 mg/kg) and high doses of physostigmine (0.1 mg/kg) interacted with morphine in the shock titration paradigm. The multiplicative interaction of morphine with scopolamine was confirmed in Experiment 3 over a wider range of doses. It was concluded that morphine and the cholinergic compounds produce antinociceptive effects through different mechanisms of the pain system."}
{"id": "PMID:709", "title": "Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives.", "content": "The effects of new thienodiazepine derivatives, such as clotiazepam and Y-7131, on normal human sleep were investigated on 5 subjects and compared to those of benzodiazepine derivatives, such as diazepam and nitrazepam. REM sleep was significantly decreased only with 2 mg of Y-7131 and rebound elevation of REM sleep did not follow in recovery 1 and 2 nights. By using partial differential REM deprivation which was designed by us, there was also no rebound elevation of REM sleep noted in recovery 2 nights following 2 mg of Y-7131 medication. REM sleep was not suppressed with 15 mg of clotiazepam, 6 mg of diazepam and 10 mg of nitrazepam when compared to the baseline night. With regard to NREM sleep, stage 2 was significantly increased with 15 mg of clotiazepam and 10 mg of nitrazepam, but stage SWS was significantly decreased with 10 mg of nitrazepam.", "contents": "Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives. The effects of new thienodiazepine derivatives, such as clotiazepam and Y-7131, on normal human sleep were investigated on 5 subjects and compared to those of benzodiazepine derivatives, such as diazepam and nitrazepam. REM sleep was significantly decreased only with 2 mg of Y-7131 and rebound elevation of REM sleep did not follow in recovery 1 and 2 nights. By using partial differential REM deprivation which was designed by us, there was also no rebound elevation of REM sleep noted in recovery 2 nights following 2 mg of Y-7131 medication. REM sleep was not suppressed with 15 mg of clotiazepam, 6 mg of diazepam and 10 mg of nitrazepam when compared to the baseline night. With regard to NREM sleep, stage 2 was significantly increased with 15 mg of clotiazepam and 10 mg of nitrazepam, but stage SWS was significantly decreased with 10 mg of nitrazepam."}
{"id": "PMID:710", "title": "Effect of two weeks' treatment with thioridazine, chlorpromazine, sulpiride and bromazepam, alone or in combination with alcohol, on learning and memory in man.", "content": "Forty paid healthy male students participated in two subacute experiments of 6 weeks each. In the first trial 20 of them received bromazepam, thioridazine, and placebo double blind cross over for 2 weeks each, and in the second trial the active agents administered to the other 20 participants were chlorpromazine and sulpiride. The tests used were paired associate learning with nonsense syllables and digit memory span. Before testing the subjects took either an alcoholic or a nonalcoholic bitter drink. As in the previous study from this laboratory, alcohol was found to impair learning capacity. Of the drugs used only bromazepam impaired learning significantly, and the combined effect of alcohol and bromazepam on learning capacity was very deleterious. The adrenolytic effect of drugs did not correlate with their effect on learning. Caution is necessary when prescribing bromazepam for active outpatients at least in doses used in this study.", "contents": "Effect of two weeks' treatment with thioridazine, chlorpromazine, sulpiride and bromazepam, alone or in combination with alcohol, on learning and memory in man. Forty paid healthy male students participated in two subacute experiments of 6 weeks each. In the first trial 20 of them received bromazepam, thioridazine, and placebo double blind cross over for 2 weeks each, and in the second trial the active agents administered to the other 20 participants were chlorpromazine and sulpiride. The tests used were paired associate learning with nonsense syllables and digit memory span. Before testing the subjects took either an alcoholic or a nonalcoholic bitter drink. As in the previous study from this laboratory, alcohol was found to impair learning capacity. Of the drugs used only bromazepam impaired learning significantly, and the combined effect of alcohol and bromazepam on learning capacity was very deleterious. The adrenolytic effect of drugs did not correlate with their effect on learning. Caution is necessary when prescribing bromazepam for active outpatients at least in doses used in this study."}
{"id": "PMID:711", "title": "Effects of chronic exposure to stressors on avoidance-escape behavior and on brain norepinephrine.", "content": "A single exposure to a severe stressor (either cold swim or inescapable shock) impairs subsequent performance in a shuttle avoidance-escape task (1), a deficit attributed to reduction in brain noradrenergic activity produced by these stressors. In the present paper, two experiments are described which examine how repeated exposure to such stressors affects (a) shuttle avoidance-escape performance (Experiment 1), and (b) aspects of brain norepinephrine metabolism (Experiment 2). Experiment 1 showed that, whereas subjects receiving the single exposure to cold swim or shock showed a large avoidance-escape deficit, subjects that received repeated exposure to these stressors for 14 days performed similarly to the control group that received no stressor. Experiment 2 showed that, whereas subjects that received one session of the inescapable shock stressor showed a lower level of norepinephrine in hypothalamus and cortex than did subjects that received no shock, subjects that received repeated exposure to inescapable shock or cold swim showed neurochemical \"habituation.\" Subjects that received repeated shock showed elevated tyrosine hydroxylase activity and no depletion of norepinephrine level, and both repeated shock and cold swim caused a decrease in uptake of 3H-norepinephrine by slices of cortex in vitro. Thus, it is concluded that the behavioral and neurochemical changes that were observed after the stressful conditions studied are consistent with the hypothesis that changes in avoidance-escape responding following exposure to these stressful events are due to changes in brain noradrenergic activity.", "contents": "Effects of chronic exposure to stressors on avoidance-escape behavior and on brain norepinephrine. A single exposure to a severe stressor (either cold swim or inescapable shock) impairs subsequent performance in a shuttle avoidance-escape task (1), a deficit attributed to reduction in brain noradrenergic activity produced by these stressors. In the present paper, two experiments are described which examine how repeated exposure to such stressors affects (a) shuttle avoidance-escape performance (Experiment 1), and (b) aspects of brain norepinephrine metabolism (Experiment 2). Experiment 1 showed that, whereas subjects receiving the single exposure to cold swim or shock showed a large avoidance-escape deficit, subjects that received repeated exposure to these stressors for 14 days performed similarly to the control group that received no stressor. Experiment 2 showed that, whereas subjects that received one session of the inescapable shock stressor showed a lower level of norepinephrine in hypothalamus and cortex than did subjects that received no shock, subjects that received repeated exposure to inescapable shock or cold swim showed neurochemical \"habituation.\" Subjects that received repeated shock showed elevated tyrosine hydroxylase activity and no depletion of norepinephrine level, and both repeated shock and cold swim caused a decrease in uptake of 3H-norepinephrine by slices of cortex in vitro. Thus, it is concluded that the behavioral and neurochemical changes that were observed after the stressful conditions studied are consistent with the hypothesis that changes in avoidance-escape responding following exposure to these stressful events are due to changes in brain noradrenergic activity."}
{"id": "PMID:725", "title": "Evaluation of combined pharmacological and psychotherapeutic treatment in patients with functional abdominal disorders.", "content": "78 patients suffering from various functional abdominal complaints have been trated in a 2 x 2 double-blind design: (a) psychotherapy with Ro 5-3350 (TH/Ro); (b) psychotherapy with placebo (TH/P); (c) Ro 5-3350 without psychotherapy (NIH/Ro); (d) placebo without psychotherapy (NTH/P). Results show that a considerable amount of improvement cannot be ascribed to the two critical factors or the interaction of both, but are due to unspecific influences in the course of treatment. Some of the results concerning the combination of TH and the psychotropic drug pose interesting questions for further research and bare implications for double-blind trials of psychotropic drugs. The results suggest that possibly properties of any psychotropic drug have to be related to a doctor-patient relationship within which the personal problems of the patient are dealt with. In order to evaluate such properties, special methodological precautions have to be taken. These will be briefly discussed.", "contents": "Evaluation of combined pharmacological and psychotherapeutic treatment in patients with functional abdominal disorders. 78 patients suffering from various functional abdominal complaints have been trated in a 2 x 2 double-blind design: (a) psychotherapy with Ro 5-3350 (TH/Ro); (b) psychotherapy with placebo (TH/P); (c) Ro 5-3350 without psychotherapy (NIH/Ro); (d) placebo without psychotherapy (NTH/P). Results show that a considerable amount of improvement cannot be ascribed to the two critical factors or the interaction of both, but are due to unspecific influences in the course of treatment. Some of the results concerning the combination of TH and the psychotropic drug pose interesting questions for further research and bare implications for double-blind trials of psychotropic drugs. The results suggest that possibly properties of any psychotropic drug have to be related to a doctor-patient relationship within which the personal problems of the patient are dealt with. In order to evaluate such properties, special methodological precautions have to be taken. These will be briefly discussed."}
{"id": "PMID:741", "title": "Role of cardiovascular and ionic changes in pathogenesis and prevention of isoprenaline-induced cardiac necrosis.", "content": "Blood pressure, heart rate, oxygen uptake, and blood values of PO2, PCO2, and pH were studied in unanesthetized rats for 8 hours. After a cardiotoxic dose of 20 mg/kg isoprenaline, s.c., blood pressure fell from 117 to 72 mm Hg, heart rate accelerated from 326 to 497 beats/minute, and cardiac work diminished by about 15%. Metabolic rate increased by about 80%, blood values of PO2 rose, and those of PCO2 fell somewhat, whereas blood pH dropped from 7.48 to 7.38, indicating metabolic acidosis. Propranolol (40 mg/kg, i.p.) and verapamil (50 mg/kg, i.p.), both of which almost completely prevented isoprenaline-induced cardiac necroses, inhibited the chronotropic and calorigenic actions of isoprenaline by about 50%. While propranolol inhibited the depressor effect of isoprenaline completely, verapamil enhanced it: blood pressure fell to 46 mm Hg. Isoprenaline-induced fall of blood pH was not prevented by either propranolol or verapamil. Decrease of blood pH and cardionecrotisation were enhanced when isoprenaline was given together with 4.8 g/kg ethanol, p.o. In conclusion, hemodynamic actions of isoprenaline, especially hypotension, seem to be nonessential for the production of cardiac necroses. Strong acidification can aggravate the cardiotoxicity of isoprenaline.", "contents": "Role of cardiovascular and ionic changes in pathogenesis and prevention of isoprenaline-induced cardiac necrosis. Blood pressure, heart rate, oxygen uptake, and blood values of PO2, PCO2, and pH were studied in unanesthetized rats for 8 hours. After a cardiotoxic dose of 20 mg/kg isoprenaline, s.c., blood pressure fell from 117 to 72 mm Hg, heart rate accelerated from 326 to 497 beats/minute, and cardiac work diminished by about 15%. Metabolic rate increased by about 80%, blood values of PO2 rose, and those of PCO2 fell somewhat, whereas blood pH dropped from 7.48 to 7.38, indicating metabolic acidosis. Propranolol (40 mg/kg, i.p.) and verapamil (50 mg/kg, i.p.), both of which almost completely prevented isoprenaline-induced cardiac necroses, inhibited the chronotropic and calorigenic actions of isoprenaline by about 50%. While propranolol inhibited the depressor effect of isoprenaline completely, verapamil enhanced it: blood pressure fell to 46 mm Hg. Isoprenaline-induced fall of blood pH was not prevented by either propranolol or verapamil. Decrease of blood pH and cardionecrotisation were enhanced when isoprenaline was given together with 4.8 g/kg ethanol, p.o. In conclusion, hemodynamic actions of isoprenaline, especially hypotension, seem to be nonessential for the production of cardiac necroses. Strong acidification can aggravate the cardiotoxicity of isoprenaline."}
{"id": "PMID:742", "title": "Alterations in norepinephrine pattern in the damaged myocardium in the rat.", "content": "In the albino rat, the evolvement of myocardial necrosis induced by a single injection of ISO was accompanied by a fall in total NE. Pretreatment with propranolol and pargyline protected against ISO-induced necrosis and myocardial hypertrophy, but did not influence the ISO-induced depletion of NE stores. The depletion of NE stores is not due to impairment in synthesis or increased intraneuronal metabolism of NE since, in ISO-treated rats, neither cardiac tyrosine hydroxylase activity nor MAO activity was altered. The decrease in endogenous NE is not due to a defect in the storage of NE. The ability of myocardium to take up and store NE returned to normal within 48 hours, whereas endogenous levels returned to normal within 5 days, even in the presence of demonstrable necrosis. Thus, there is lack of correlation between chemical and morphological changes, since catecholamine depletion occurred in the absence of morphologically demonstrable tissue injury, and the function of the adrenergic neuron returns to normal in the presence of demonstrable necrosis.", "contents": "Alterations in norepinephrine pattern in the damaged myocardium in the rat. In the albino rat, the evolvement of myocardial necrosis induced by a single injection of ISO was accompanied by a fall in total NE. Pretreatment with propranolol and pargyline protected against ISO-induced necrosis and myocardial hypertrophy, but did not influence the ISO-induced depletion of NE stores. The depletion of NE stores is not due to impairment in synthesis or increased intraneuronal metabolism of NE since, in ISO-treated rats, neither cardiac tyrosine hydroxylase activity nor MAO activity was altered. The decrease in endogenous NE is not due to a defect in the storage of NE. The ability of myocardium to take up and store NE returned to normal within 48 hours, whereas endogenous levels returned to normal within 5 days, even in the presence of demonstrable necrosis. Thus, there is lack of correlation between chemical and morphological changes, since catecholamine depletion occurred in the absence of morphologically demonstrable tissue injury, and the function of the adrenergic neuron returns to normal in the presence of demonstrable necrosis."}
{"id": "PMID:743", "title": "Prevention of myocardial Ca overload and necrotization by Mg and K salts or acidosis.", "content": "The crucial point in the pathogenesis of isoproterenol-induced myocardial necrotization is an abundant intracellular Ca accumulation leading to high energy phosphate exhaustion. Accordingly, in the early stage of the isoproterenol-induced necrotization process, the onset of ATP and creatine phosphate breakdown strictly parallels the acute Ca gain. In this type of necrosis, the Mg losses from the myocardium appear as a concomitant phenomenon. The hearts can be protected against the deleterious Ca overload and necrotization by increasing the plasma concentration of Mg, K, or H ions in order to counterbalance Ca according to the ration (see article). On the other hand, if Mg, K, or H ion concentrations are too low, isoproterenol-induced Ca uptake and myocardial lesions are potentiated.", "contents": "Prevention of myocardial Ca overload and necrotization by Mg and K salts or acidosis. The crucial point in the pathogenesis of isoproterenol-induced myocardial necrotization is an abundant intracellular Ca accumulation leading to high energy phosphate exhaustion. Accordingly, in the early stage of the isoproterenol-induced necrotization process, the onset of ATP and creatine phosphate breakdown strictly parallels the acute Ca gain. In this type of necrosis, the Mg losses from the myocardium appear as a concomitant phenomenon. The hearts can be protected against the deleterious Ca overload and necrotization by increasing the plasma concentration of Mg, K, or H ions in order to counterbalance Ca according to the ration (see article). On the other hand, if Mg, K, or H ion concentrations are too low, isoproterenol-induced Ca uptake and myocardial lesions are potentiated."}
{"id": "PMID:745", "title": "Explanation of the stimulation of microsomal N-demethylation reactions by soluble supernatant fraction.", "content": "Addition of the cell soluble supernatant fraction to an assay medium containing NADPH generating system, mixed function oxidase substrate and microsomes, resulted in a stimulation of drug metabolism ranging from 12-75%. This stimulation was observed only when the supply of DADPH generating system (isocitric dehydrogenase or glucose 6 phosphate dehydrogenase) was insufficient, leading to a NADPH oxidation rate which was greater than the rate of reduction of NADP+ during the oxidation of a drug. Hence, under our assay conditions, the soluble supernate (SS) is only providing sufficient NADPH generator, and possibly relieving inhibition by the generated NADP+. Finally, microsomal lipid peroxidation measurements under these same conditions indicate negligible to no peroxidation activity in the absence of SS.", "contents": "Explanation of the stimulation of microsomal N-demethylation reactions by soluble supernatant fraction. Addition of the cell soluble supernatant fraction to an assay medium containing NADPH generating system, mixed function oxidase substrate and microsomes, resulted in a stimulation of drug metabolism ranging from 12-75%. This stimulation was observed only when the supply of DADPH generating system (isocitric dehydrogenase or glucose 6 phosphate dehydrogenase) was insufficient, leading to a NADPH oxidation rate which was greater than the rate of reduction of NADP+ during the oxidation of a drug. Hence, under our assay conditions, the soluble supernate (SS) is only providing sufficient NADPH generator, and possibly relieving inhibition by the generated NADP+. Finally, microsomal lipid peroxidation measurements under these same conditions indicate negligible to no peroxidation activity in the absence of SS."}
{"id": "PMID:746", "title": "An attempt to correlated analgesia to changes in brain neuromediators in rats.", "content": "The analgesic activity of delta9THC, morphine and sodium salicylate was studied concomitantly with changes in brain stem levels of 5HT, 5HIAA, DA and NA. The results show that a correlation exists between analgesia and changes in the serotonergic system of the brain stem. Furthermore morphine sulfate was found to increase the DA concentration of the brain stem while delta9THC increased NA levels. We conclude that serotonergic system may be of major importance in analgesia while simultaneous changes in this system and/or the DA and NA systems may lead to a more pronounced analgesic activity.", "contents": "An attempt to correlated analgesia to changes in brain neuromediators in rats. The analgesic activity of delta9THC, morphine and sodium salicylate was studied concomitantly with changes in brain stem levels of 5HT, 5HIAA, DA and NA. The results show that a correlation exists between analgesia and changes in the serotonergic system of the brain stem. Furthermore morphine sulfate was found to increase the DA concentration of the brain stem while delta9THC increased NA levels. We conclude that serotonergic system may be of major importance in analgesia while simultaneous changes in this system and/or the DA and NA systems may lead to a more pronounced analgesic activity."}
{"id": "PMID:747", "title": "Colorimetric determination of 5-aminosalicylic acid and its N-acetylated metabolite on urine and feces.", "content": "A simple and convenient colorimetric method is described for the quantitative determination of 5-aminosalicylic acid (5-ASA) and N-acetyl-5-ASA in urine and feces after oral administration of salicylazosulfa-pyridine (SASP), the drug of choice in the treatment of ulcerative colitis. N-acetyl-5-ASA is extracted directly from the acidified biological specimen, deacetylated, and the liberated 5-ASA subjected to a modified Bratton-Marshall reaction. The 5-ASA present in the specimen must be acetylated with acetic anhydride prior to extraction. The violet colored product of the Bratton-Marshall reaction has a lambdamax of 560 nm and conforms to Beer's law over the concentration range of 0-70 umg/ml. Average recoveries (+/- S.D., N = 6) OF 5-ASA added to rat and human urine and rat fecal homogenates were 91.6 +/- 4.9%, 102 +/- 6.0%, and 71.0 +/- 4.8%, respectively. Interference by SASP and its sulfapyridine metabolities is negligible. As demonstrated, the colorimetric method is of sufficient sensitivity for application in most metabolic and pharmacokinetic studies conducted with SASP in laboratory animals and man.", "contents": "Colorimetric determination of 5-aminosalicylic acid and its N-acetylated metabolite on urine and feces. A simple and convenient colorimetric method is described for the quantitative determination of 5-aminosalicylic acid (5-ASA) and N-acetyl-5-ASA in urine and feces after oral administration of salicylazosulfa-pyridine (SASP), the drug of choice in the treatment of ulcerative colitis. N-acetyl-5-ASA is extracted directly from the acidified biological specimen, deacetylated, and the liberated 5-ASA subjected to a modified Bratton-Marshall reaction. The 5-ASA present in the specimen must be acetylated with acetic anhydride prior to extraction. The violet colored product of the Bratton-Marshall reaction has a lambdamax of 560 nm and conforms to Beer's law over the concentration range of 0-70 umg/ml. Average recoveries (+/- S.D., N = 6) OF 5-ASA added to rat and human urine and rat fecal homogenates were 91.6 +/- 4.9%, 102 +/- 6.0%, and 71.0 +/- 4.8%, respectively. Interference by SASP and its sulfapyridine metabolities is negligible. As demonstrated, the colorimetric method is of sufficient sensitivity for application in most metabolic and pharmacokinetic studies conducted with SASP in laboratory animals and man."}
{"id": "PMID:748", "title": "[Pressures, blood gases, pH, lactate and pyruvate concentrations in the portal venous blood in patients after laparotomy during the first 9 days (author's transl)].", "content": "In 24 patients (16 women, 8 men, mean age 60 years), who underwent abdominal operations and who had a uncomplicated postoperative course, a teflon-tube was inserted into the portal vein at the end of laparotomy and remained there for maximal 9 days. The mean values of the portal venous pressure as well as of the portal-central venous pressure gradient are unchanged during the period of all 9 days and are between 7,4 and 7,9 mmHg, between 5,6 and 6,9 mmHg respectively. The arterio-portal venous 0(2)-content difference shows in the mean no fluctuations and is about 2 Vol.%. On the first postoperative day the lactic and pyruvic acid concentrations in the artery and portal vein are moderately, but significantly elevated and decrease to normal values until day 7. - 9.", "contents": "[Pressures, blood gases, pH, lactate and pyruvate concentrations in the portal venous blood in patients after laparotomy during the first 9 days (author's transl)]. In 24 patients (16 women, 8 men, mean age 60 years), who underwent abdominal operations and who had a uncomplicated postoperative course, a teflon-tube was inserted into the portal vein at the end of laparotomy and remained there for maximal 9 days. The mean values of the portal venous pressure as well as of the portal-central venous pressure gradient are unchanged during the period of all 9 days and are between 7,4 and 7,9 mmHg, between 5,6 and 6,9 mmHg respectively. The arterio-portal venous 0(2)-content difference shows in the mean no fluctuations and is about 2 Vol.%. On the first postoperative day the lactic and pyruvic acid concentrations in the artery and portal vein are moderately, but significantly elevated and decrease to normal values until day 7. - 9."}
{"id": "PMID:749", "title": "Biochemical and biophysical changes in guinea pigs after acute head injury.", "content": "Animal experiments were set up mainly to derive additional diagnostic data from the study of biochemical changes after acute head injury. In standardized experiments guinea pigs were subjected in groups of 20 to three identical head injuries, each of either 1.0 J or 1.5 J intensity. The trauma was likely to result in a concussion or contusion syndrome similar to that found in man; 40 animals served as controls. During the 60 min after injury observation and measurement of body functions did not reveal signs of a shock-like condition or hypoxaemia in the traumatized animals compared with control animals. Superficial anaesthesia probably did not influence the findings. Temperature and respiration were altered significantly in all the animals receiving head injuries. Blood gas analysis showed a decrease of standard bicarbonate only after the 1.5 J injury but even though hypoxaemia was not present 2,3-diphosphoglycerate values and P50 increased, compared with the control animals. The fall of plasma lipid concentrations reported probably had to be seen as a sympathomimetic effect of the minor (1.0 J) trauma. Of special significance was the increased activity of malate dehydrogenase and aldolase, found only in the blood of severely traumatized animals, as this could serve as an early diagnostic aid for evaluating head injuries.", "contents": "Biochemical and biophysical changes in guinea pigs after acute head injury. Animal experiments were set up mainly to derive additional diagnostic data from the study of biochemical changes after acute head injury. In standardized experiments guinea pigs were subjected in groups of 20 to three identical head injuries, each of either 1.0 J or 1.5 J intensity. The trauma was likely to result in a concussion or contusion syndrome similar to that found in man; 40 animals served as controls. During the 60 min after injury observation and measurement of body functions did not reveal signs of a shock-like condition or hypoxaemia in the traumatized animals compared with control animals. Superficial anaesthesia probably did not influence the findings. Temperature and respiration were altered significantly in all the animals receiving head injuries. Blood gas analysis showed a decrease of standard bicarbonate only after the 1.5 J injury but even though hypoxaemia was not present 2,3-diphosphoglycerate values and P50 increased, compared with the control animals. The fall of plasma lipid concentrations reported probably had to be seen as a sympathomimetic effect of the minor (1.0 J) trauma. Of special significance was the increased activity of malate dehydrogenase and aldolase, found only in the blood of severely traumatized animals, as this could serve as an early diagnostic aid for evaluating head injuries."}
{"id": "PMID:750", "title": "Total brain ischaemia in dogs: cerebral physiological and metabolic changes after 15 minutes of circulatory arrest.", "content": "Cross-clamping of the ascending aorta in dogs for 15 min produced severe neurological deficit, observed for up to 20 h. Immediately after restoration of the circulation, the intracranial pressure in the cisterna magna increased transiently to a mean peak of 22.8 Torr (SD +/- 1.7) because of a compensatory increase in systemic arterial pressure, without a fall in cerebral perfusion pressure. The intracranial pressure returned to control values 15-30 min after ischaemia and showed no secondary rise during the 8 h of observation. The electroencephalogram became isoelectric 34 +/- 6.5 s (mean +/-SD) after circulatory occlusion, and was abnormal when it reappeared 5 h 36 min (SD +/- 2 h 4 min) after the circulation was restored. The electrical impedance of the brain increased immediately after ischaemia and returned rapidly towards pre-ischaemic values during re-perfusion. The cerebral water had not increased measurably 4 h after ischaemia. After ischaemia, the lactate concentration in the cerebrospinal fluid increased to 4.7 mequiv./1(SEM +/-0.1) and the pH decreased to 7.17 (SEM +/-0.02); both returned to control values after 3.5 h. The cerebral glucose uptake was decreased 35 min after ischaemia, cerebral oxygen uptake remained unchanged but cerebral blood flow decreased (P less than 0.05 at 90 min). Immediately after cardiac arrest, recovery was impaired more by the presence of focal abnormal brain perfusion than by intracranial hypertension.", "contents": "Total brain ischaemia in dogs: cerebral physiological and metabolic changes after 15 minutes of circulatory arrest. Cross-clamping of the ascending aorta in dogs for 15 min produced severe neurological deficit, observed for up to 20 h. Immediately after restoration of the circulation, the intracranial pressure in the cisterna magna increased transiently to a mean peak of 22.8 Torr (SD +/- 1.7) because of a compensatory increase in systemic arterial pressure, without a fall in cerebral perfusion pressure. The intracranial pressure returned to control values 15-30 min after ischaemia and showed no secondary rise during the 8 h of observation. The electroencephalogram became isoelectric 34 +/- 6.5 s (mean +/-SD) after circulatory occlusion, and was abnormal when it reappeared 5 h 36 min (SD +/- 2 h 4 min) after the circulation was restored. The electrical impedance of the brain increased immediately after ischaemia and returned rapidly towards pre-ischaemic values during re-perfusion. The cerebral water had not increased measurably 4 h after ischaemia. After ischaemia, the lactate concentration in the cerebrospinal fluid increased to 4.7 mequiv./1(SEM +/-0.1) and the pH decreased to 7.17 (SEM +/-0.02); both returned to control values after 3.5 h. The cerebral glucose uptake was decreased 35 min after ischaemia, cerebral oxygen uptake remained unchanged but cerebral blood flow decreased (P less than 0.05 at 90 min). Immediately after cardiac arrest, recovery was impaired more by the presence of focal abnormal brain perfusion than by intracranial hypertension."}
{"id": "PMID:751", "title": "Oxygen and carbon dioxide dissociation of duck blood.", "content": "Oxygen and CO2 dissociation of duck blood was studied in blood samples equilibrated with known gas mixtures at the bird's body temperature (41 degrees C) and analyzed in the Van Slyke manometric apparatus and in pH electrodes. At various pH values between 7.38 and 7.55 the Hill plots yielded straight and parallel lines over a wide range of O2 saturation, the Hill coefficient being 2.9. Half saturation pressure P50 at pH = 7.50 was 36 torr. The Bohr effect factor was -0.53. Buffering properties were analyzed by equilibrating blood samples with gas mixtures of different PCO2 at 41 degrees C. The buffer value for whole blood in the range of 3-7% CO2 was 19.3 mMol-L-1-pH-1, the buffer value for true plasma 22.9 mMol-L-1-pH-1. The CO2 dissociation curve constructed using the buffer values had a slope of 0.17 mMol-L-1-torr-1 in the PCO2 range from 40 to 50 torr. The CO2 content of oxygenated blood at PCO2 = 40 torr was 21.7 mMol-L-1. The Haldane effect factor at PCO2 = 35 torr equalled 0.30 mMol of combined CO2 per mMol HbO2. With the values of PO2, PCO2 and pH measured in arterial blood of undisturbed and unrestrained, resting ducks effective dissociation curves for both O2 and CO2 were constructed assuming a metabolic R.Q. of 0.8. These curves are expected to resemble closely the actual in vitro dissociation curves of resting ducks.", "contents": "Oxygen and carbon dioxide dissociation of duck blood. Oxygen and CO2 dissociation of duck blood was studied in blood samples equilibrated with known gas mixtures at the bird's body temperature (41 degrees C) and analyzed in the Van Slyke manometric apparatus and in pH electrodes. At various pH values between 7.38 and 7.55 the Hill plots yielded straight and parallel lines over a wide range of O2 saturation, the Hill coefficient being 2.9. Half saturation pressure P50 at pH = 7.50 was 36 torr. The Bohr effect factor was -0.53. Buffering properties were analyzed by equilibrating blood samples with gas mixtures of different PCO2 at 41 degrees C. The buffer value for whole blood in the range of 3-7% CO2 was 19.3 mMol-L-1-pH-1, the buffer value for true plasma 22.9 mMol-L-1-pH-1. The CO2 dissociation curve constructed using the buffer values had a slope of 0.17 mMol-L-1-torr-1 in the PCO2 range from 40 to 50 torr. The CO2 content of oxygenated blood at PCO2 = 40 torr was 21.7 mMol-L-1. The Haldane effect factor at PCO2 = 35 torr equalled 0.30 mMol of combined CO2 per mMol HbO2. With the values of PO2, PCO2 and pH measured in arterial blood of undisturbed and unrestrained, resting ducks effective dissociation curves for both O2 and CO2 were constructed assuming a metabolic R.Q. of 0.8. These curves are expected to resemble closely the actual in vitro dissociation curves of resting ducks."}
{"id": "PMID:752", "title": "First apparent dissociation constant of carbonic acid, pK'1, of plasma and erythrocytes.", "content": "The first apparent dissociation constant of carbonic acid, pK'1, of plasma and red cells was determined on venous blood of ten healthy, adult, male, human subjects. pH and PCO2 of plasma and red cells were analyzed electrometrically and a micromanometric method was used for the determination of total carbon dioxide content. Erythrocyte carbamino hemoglobin levels were estimated and used for the correction of erythrocyte pK'1. Each blood sample was subjected to the following regimen before centrifugation, 1) As drawn from the antecubital vein, 2) Oxygenated with a 5% CO2, O2 balance gas mixture, and 3) Reduced with a 5% CO2, N2 balance gas mixture. pK'1 of plasma and red cells are presented: (see article). The consistently larger values for red cell pK'1 than the respective plasma data may be attributed to the greater amount of carbamino hemoglobin concentration present in the erythrocytes. A simplified method for the calculation of erythrocyte bicarbonate concentration using the experimentally determined red cell pK'1 value has been formulated. The method involves the use of a regression equation relating plasma and red cell pH, the equivalence of plasma and red cell PCO2, along with the experimentally determined red cell pK'1.", "contents": "First apparent dissociation constant of carbonic acid, pK'1, of plasma and erythrocytes. The first apparent dissociation constant of carbonic acid, pK'1, of plasma and red cells was determined on venous blood of ten healthy, adult, male, human subjects. pH and PCO2 of plasma and red cells were analyzed electrometrically and a micromanometric method was used for the determination of total carbon dioxide content. Erythrocyte carbamino hemoglobin levels were estimated and used for the correction of erythrocyte pK'1. Each blood sample was subjected to the following regimen before centrifugation, 1) As drawn from the antecubital vein, 2) Oxygenated with a 5% CO2, O2 balance gas mixture, and 3) Reduced with a 5% CO2, N2 balance gas mixture. pK'1 of plasma and red cells are presented: (see article). The consistently larger values for red cell pK'1 than the respective plasma data may be attributed to the greater amount of carbamino hemoglobin concentration present in the erythrocytes. A simplified method for the calculation of erythrocyte bicarbonate concentration using the experimentally determined red cell pK'1 value has been formulated. The method involves the use of a regression equation relating plasma and red cell pH, the equivalence of plasma and red cell PCO2, along with the experimentally determined red cell pK'1."}
{"id": "PMID:753", "title": "The effects of changes in pH and PCO2 in blood and water on breathing in rainbow trout, Salmo gairdneri.", "content": "The effect of sustained hypercapnia on the acid-base balance and gill ventilation in rainbow trout, Salmo gairdneri, was studied. The response to an increase in PICO2 from 0.3 to 5.2 mm Hg was a five-fold increase in gill ventilation volume and a slight increase in breathing frequency. There was a concomitant rise in PACO2 and an immediate fall in pHa. If PICO2 was maintained at 5.2 mm Hg for several days, ventilation volume gradually returned to the initial, prehypercapnic level within three days. Arterial pH also returned to the initial level within 2-3 days. These results are consistent with the hypothesis that under these conditions fish regulate pH via HCO3/C1 exchange across the gills rather than by changes in ventilation and subsequent adjustment of PACO2. A reduction in environmental pH causes a reduction in pHa but only a slow gradual increase in VG. Injections of HC1 or NaHCO3 into the blood have opposite effects on pHa but both cause a marked increase in VG. It is concluded that a rise in PACO2 results in a rise in VG and that changes in pH in blood or water have little direct effect on VG in rainbow trout. Possible location for receptors involved in this reflex response are discussed.", "contents": "The effects of changes in pH and PCO2 in blood and water on breathing in rainbow trout, Salmo gairdneri. The effect of sustained hypercapnia on the acid-base balance and gill ventilation in rainbow trout, Salmo gairdneri, was studied. The response to an increase in PICO2 from 0.3 to 5.2 mm Hg was a five-fold increase in gill ventilation volume and a slight increase in breathing frequency. There was a concomitant rise in PACO2 and an immediate fall in pHa. If PICO2 was maintained at 5.2 mm Hg for several days, ventilation volume gradually returned to the initial, prehypercapnic level within three days. Arterial pH also returned to the initial level within 2-3 days. These results are consistent with the hypothesis that under these conditions fish regulate pH via HCO3/C1 exchange across the gills rather than by changes in ventilation and subsequent adjustment of PACO2. A reduction in environmental pH causes a reduction in pHa but only a slow gradual increase in VG. Injections of HC1 or NaHCO3 into the blood have opposite effects on pHa but both cause a marked increase in VG. It is concluded that a rise in PACO2 results in a rise in VG and that changes in pH in blood or water have little direct effect on VG in rainbow trout. Possible location for receptors involved in this reflex response are discussed."}
{"id": "PMID:783", "title": "The effect of pH upon fluoride uptake in intact enamel.", "content": "The relationship between pH and fluoride uptake in intact enamel of permanent premolars was investigated by using: (1) a sodium fluoride dentifrice, (2) a potassium fluoride + manganese chloride dentifrice, and (3) a sodium fluoride solution of the same fluoride concentration. The first part of this paper deals with the in vitro uptake of fluoride from dentifrice slurries and from sodium fluoride solutions of different pH ranging from 7.1 to 4.5. This investigation showed that there was no significant difference between the agents but that the effect of the pH was significant. The uptake of fluoride in the form of fluorapatite was more than five times larger at the lower pH level. The second part of the paper deals with the rate of fluoride uptake (increase in fluoride content) from dentifrices in the same pH range. It was shown that the three agents gave the same initial rate of fluoride uptake (about 50 parts/10(6)/min) at pH 6 and that the rate of fluoride uptake in the outer layer of the enamel was proportional to the hydrogen ion activity.", "contents": "The effect of pH upon fluoride uptake in intact enamel. The relationship between pH and fluoride uptake in intact enamel of permanent premolars was investigated by using: (1) a sodium fluoride dentifrice, (2) a potassium fluoride + manganese chloride dentifrice, and (3) a sodium fluoride solution of the same fluoride concentration. The first part of this paper deals with the in vitro uptake of fluoride from dentifrice slurries and from sodium fluoride solutions of different pH ranging from 7.1 to 4.5. This investigation showed that there was no significant difference between the agents but that the effect of the pH was significant. The uptake of fluoride in the form of fluorapatite was more than five times larger at the lower pH level. The second part of the paper deals with the rate of fluoride uptake (increase in fluoride content) from dentifrices in the same pH range. It was shown that the three agents gave the same initial rate of fluoride uptake (about 50 parts/10(6)/min) at pH 6 and that the rate of fluoride uptake in the outer layer of the enamel was proportional to the hydrogen ion activity."}
{"id": "PMID:784", "title": "Determination of inorganic pyrophosphatase in rat odontoblast layer by a radiochemical method.", "content": "The enzyme inorganic pyrophosphatase (PPiase, EC 3.6.1.1) from the odontoblastic layer of rat incisors has been studied by means of a radiochemical micromethod. The enzyme was incubated with 32P-pyrophosphate in tris-HCl buffer at 37 degrees C. The reaction was linear with time for at least 45 min, and the pH optimum was found to be 8.8, independent of the amount of pyrophosphate present. Heating the enzyme at 56 degrees C inhibited the enzyme activity rapidly, Mg2+ ions activated the enzyme by 15% at an ion concentration of 4 mM, while higher concentrations were inhibitory. Ca2+ ions and PO43-ions inhibited the enzyme at all concentrations. F- ions did not affect the PPiase at concentrations below 8 mM, whereas higher concentrations had an inhibiting effect. Urea was found to inhibit the enzyme at concentrations above 1.5 M, while EDTA was a strong inhibitor at very low concentrations. The characteristics of PPiase agree well with the properties of the enzyme nonspecific alkaline phosphatase (EC 3.1.3.1.) studied earlier.", "contents": "Determination of inorganic pyrophosphatase in rat odontoblast layer by a radiochemical method. The enzyme inorganic pyrophosphatase (PPiase, EC 3.6.1.1) from the odontoblastic layer of rat incisors has been studied by means of a radiochemical micromethod. The enzyme was incubated with 32P-pyrophosphate in tris-HCl buffer at 37 degrees C. The reaction was linear with time for at least 45 min, and the pH optimum was found to be 8.8, independent of the amount of pyrophosphate present. Heating the enzyme at 56 degrees C inhibited the enzyme activity rapidly, Mg2+ ions activated the enzyme by 15% at an ion concentration of 4 mM, while higher concentrations were inhibitory. Ca2+ ions and PO43-ions inhibited the enzyme at all concentrations. F- ions did not affect the PPiase at concentrations below 8 mM, whereas higher concentrations had an inhibiting effect. Urea was found to inhibit the enzyme at concentrations above 1.5 M, while EDTA was a strong inhibitor at very low concentrations. The characteristics of PPiase agree well with the properties of the enzyme nonspecific alkaline phosphatase (EC 3.1.3.1.) studied earlier."}
{"id": "PMID:785", "title": "Assessment of denture plaque pH in subjects with and without denture stomatitis.", "content": "To evaluate the \"resting\" pH and induced pH changes in denture plaque, soft deposits were collected from the fitting surface of the denture, pooled and suspended in water. Plaque pH was determined with microelectrode equipment before and after mouth rinsing with a sucrose solution. A characteristic level in the \"resting\" pH of denture plaque was found in most of 12 subjects tested. pH values below the baseline level were recorded for more than 2 h after a rinse. The pH depressions were more pronounced in maxillary than in mandibular plaque. Further, the pH minima tended to be lower in subjects with denture stomatitis than in controls. No clear relationship could be established between the \"resting\" pH and the concentration of Candida hyphae in denture smears or palatal inflammation.", "contents": "Assessment of denture plaque pH in subjects with and without denture stomatitis. To evaluate the \"resting\" pH and induced pH changes in denture plaque, soft deposits were collected from the fitting surface of the denture, pooled and suspended in water. Plaque pH was determined with microelectrode equipment before and after mouth rinsing with a sucrose solution. A characteristic level in the \"resting\" pH of denture plaque was found in most of 12 subjects tested. pH values below the baseline level were recorded for more than 2 h after a rinse. The pH depressions were more pronounced in maxillary than in mandibular plaque. Further, the pH minima tended to be lower in subjects with denture stomatitis than in controls. No clear relationship could be established between the \"resting\" pH and the concentration of Candida hyphae in denture smears or palatal inflammation."}
{"id": "PMID:786", "title": "Bioluminescence assay of enzymes obtained from buccal epithelium by superficial scraping.", "content": "A method is presented for the simultaneous assay of buccal enzymes by measuring reduced nicotinamide adenine dinucleotide and adenosine triphosphate with the aid of the bioluminescence of luciferase extracts. The activity of glucose-6-phosphate dehydrogenase (G6PDH) was shown earlier to be increased in homogeneous leukoplakias of the oral mucosa. Since smoking has been implicated as an etiologic factor of leukoplakia, G6PDH was measured in the normal buccal epithelium of cigarette smokers. No difference was found in the activity of G6PDH between smokers and nonsmokers when related to the activity of pyruvate kinase, which is known to be invariable in healthy and leukoplakic oral mucosa. A new compact kinetic luminescence analyzer is briefly described.", "contents": "Bioluminescence assay of enzymes obtained from buccal epithelium by superficial scraping. A method is presented for the simultaneous assay of buccal enzymes by measuring reduced nicotinamide adenine dinucleotide and adenosine triphosphate with the aid of the bioluminescence of luciferase extracts. The activity of glucose-6-phosphate dehydrogenase (G6PDH) was shown earlier to be increased in homogeneous leukoplakias of the oral mucosa. Since smoking has been implicated as an etiologic factor of leukoplakia, G6PDH was measured in the normal buccal epithelium of cigarette smokers. No difference was found in the activity of G6PDH between smokers and nonsmokers when related to the activity of pyruvate kinase, which is known to be invariable in healthy and leukoplakic oral mucosa. A new compact kinetic luminescence analyzer is briefly described."}
{"id": "PMID:789", "title": "Allogeneic marrow transplantation for the treatment of leukaemia. A review.", "content": "22 HL-A antigen and mixed leukocyte culture-matched sibling bone marrow transplants were attempted in patients with acute leukaemia (at the National Cancer Institute) to define the toxicities of four different immunosuppressive regimens, the complications associated with warrow engraftment and antileukaemic effect. 73% (16/22) were engrafted as indicated by a change to donor red blood cells (RBC) type, leukocyte, immunoglobulin allotype or by the speed of morrow repopulation and the occurrence of the Graft Versus Host Disease (GVHD). 12 of 16 (75%) successful engrafted patients developed  GVHD. The current published results of clinical bone marrow transplantation from major centers has been reviewed and will be discussed in relationship to current clinical complications associated with bone marrow transplantation.", "contents": "Allogeneic marrow transplantation for the treatment of leukaemia. A review. 22 HL-A antigen and mixed leukocyte culture-matched sibling bone marrow transplants were attempted in patients with acute leukaemia (at the National Cancer Institute) to define the toxicities of four different immunosuppressive regimens, the complications associated with warrow engraftment and antileukaemic effect. 73% (16/22) were engrafted as indicated by a change to donor red blood cells (RBC) type, leukocyte, immunoglobulin allotype or by the speed of morrow repopulation and the occurrence of the Graft Versus Host Disease (GVHD). 12 of 16 (75%) successful engrafted patients developed  GVHD. The current published results of clinical bone marrow transplantation from major centers has been reviewed and will be discussed in relationship to current clinical complications associated with bone marrow transplantation."}
{"id": "PMID:792", "title": "Current status of treatment of pneumonia.", "content": "Proper treatment of pneumonia is dependent upon a correct diagnosis. Pneumonia may be due to infectious agents, allergic phenomena, or chemical causes. Treatment regimens are outlined for the various types of pneumonia--pneumococcal, staphylococcal, fungal, and pneumonia due to gram-negative and anaerobic gram-negative bacilli, to Blastomyces dermatitidis, and to the parasite Pneumocystis carinii. In discussing current concepts of treatment, several well-known methods are emphasized, as well as newer developments, knowledge of which is essential for optimal treatment of pneumonia.", "contents": "Current status of treatment of pneumonia. Proper treatment of pneumonia is dependent upon a correct diagnosis. Pneumonia may be due to infectious agents, allergic phenomena, or chemical causes. Treatment regimens are outlined for the various types of pneumonia--pneumococcal, staphylococcal, fungal, and pneumonia due to gram-negative and anaerobic gram-negative bacilli, to Blastomyces dermatitidis, and to the parasite Pneumocystis carinii. In discussing current concepts of treatment, several well-known methods are emphasized, as well as newer developments, knowledge of which is essential for optimal treatment of pneumonia."}
{"id": "PMID:795", "title": "'Picture frame' fibres in a carrier of the trait for malignant hyperpyrexia.", "content": "A member of a family which was known to be susceptible to malignant hyperpyrexia, who was identified as a carrier by the presence of an elevated serum creatine-phosphokinase, has been investigated further. Muscle was examined biochemically, and the study included the sarcoplasmic ATPase-activity, actinomycin, Mg2+ ATPase activity, ATP, phosphocreatine and glucose-6-phosphate. In addition, the calcium uptake by the sarcoplasmic reticulum was studied. The histochemical analysis of the muscle revealed the presence of a new fibre type characterised by a dense rim of ATPase activity, which gives the impression of a 'picture-frame'. Ultramicroscopic study revealed changes in the mitochondria and areas of myofibrillar disruption with swelling of the sarcoplasmic reticulum.", "contents": "'Picture frame' fibres in a carrier of the trait for malignant hyperpyrexia. A member of a family which was known to be susceptible to malignant hyperpyrexia, who was identified as a carrier by the presence of an elevated serum creatine-phosphokinase, has been investigated further. Muscle was examined biochemically, and the study included the sarcoplasmic ATPase-activity, actinomycin, Mg2+ ATPase activity, ATP, phosphocreatine and glucose-6-phosphate. In addition, the calcium uptake by the sarcoplasmic reticulum was studied. The histochemical analysis of the muscle revealed the presence of a new fibre type characterised by a dense rim of ATPase activity, which gives the impression of a 'picture-frame'. Ultramicroscopic study revealed changes in the mitochondria and areas of myofibrillar disruption with swelling of the sarcoplasmic reticulum."}
{"id": "PMID:796", "title": "The GP dilemma. Recommendations and synopsis of a student conference.", "content": "The proceedings of a conference organised by students are reported. The present standing of the general practitioner and his need in different societies are equated and the obvious deficiencies are considered. Such themes as maldistribution, service and education are discussed. Resolutions derived from the conference are reported in full.", "contents": "The GP dilemma. Recommendations and synopsis of a student conference. The proceedings of a conference organised by students are reported. The present standing of the general practitioner and his need in different societies are equated and the obvious deficiencies are considered. Such themes as maldistribution, service and education are discussed. Resolutions derived from the conference are reported in full."}
{"id": "PMID:800", "title": "Gastric emptying of liquids after different vagotomies and pyloroplasty.", "content": "Gastric emptying of five liquid meals which differ in their physicochemical properties have been measured in control dogs and dogs that have received a Heinecke-Mikulicz pyloroplasty alone, proximal gastric vagotomy without drainage, selective gastric vagotomy and pyloroplasty and truncal vagotomy and pyloroplasty. The first two phases of emptying have been computed by the method of least squares to obtain a logarithmic-linear pattern and are expressed as relative rates: The initial post-ingestion process is characterized by beta or the average relative rate of emptying in the first ten minutes, the basic or exponential rate as beta and the change in rate from the initial to basic pattern as deltabeta. Each measure of gastric emptying was statistically analyzed to determine specific differences in rates between the operations studied. We confirmed the earlier claims that pyloroplasty alone does not change the emptying rate of liquid meals. Each measure or phase of emptying varies consistently across the operations from meal to meal tested. Initial emptying after all three vagotomies is significantly faster than control with progressive rate increases as proximal gastric vagotomy is compared with selective gastric vagotomy with pyloroplasty and with truncal vagotomy with pyloroplasty, probably indicative of gastric fundal loss of accommodation to volume distention after denervation. The basic exponential pattern of emptying is not lost after any of the operations studied. The basic rate after proximal gastric vagotomy and selective gastric vagotomy with pyloroplasty is nearly identical, slightly delayed from the control rate and significantly slower than the more rapid rate after truncal vagotomy with pyloroplasty. Possible explanations for these are discussed and imply a particular importance of the hepatic and celiac vagal fibers, sectioned only with truncal vagotomy, in the regulation of gastric emptying of liquids.", "contents": "Gastric emptying of liquids after different vagotomies and pyloroplasty. Gastric emptying of five liquid meals which differ in their physicochemical properties have been measured in control dogs and dogs that have received a Heinecke-Mikulicz pyloroplasty alone, proximal gastric vagotomy without drainage, selective gastric vagotomy and pyloroplasty and truncal vagotomy and pyloroplasty. The first two phases of emptying have been computed by the method of least squares to obtain a logarithmic-linear pattern and are expressed as relative rates: The initial post-ingestion process is characterized by beta or the average relative rate of emptying in the first ten minutes, the basic or exponential rate as beta and the change in rate from the initial to basic pattern as deltabeta. Each measure of gastric emptying was statistically analyzed to determine specific differences in rates between the operations studied. We confirmed the earlier claims that pyloroplasty alone does not change the emptying rate of liquid meals. Each measure or phase of emptying varies consistently across the operations from meal to meal tested. Initial emptying after all three vagotomies is significantly faster than control with progressive rate increases as proximal gastric vagotomy is compared with selective gastric vagotomy with pyloroplasty and with truncal vagotomy with pyloroplasty, probably indicative of gastric fundal loss of accommodation to volume distention after denervation. The basic exponential pattern of emptying is not lost after any of the operations studied. The basic rate after proximal gastric vagotomy and selective gastric vagotomy with pyloroplasty is nearly identical, slightly delayed from the control rate and significantly slower than the more rapid rate after truncal vagotomy with pyloroplasty. Possible explanations for these are discussed and imply a particular importance of the hepatic and celiac vagal fibers, sectioned only with truncal vagotomy, in the regulation of gastric emptying of liquids."}
{"id": "PMID:801", "title": "Pancreatic enzyme response with an elemental diet.", "content": "Elemental diets can maintain or slightly improve the nutritional status without a major stimulatory effect on the pancreas. Six dogs were maintained with a regular chow diet, switched to an elemental diet and, subsequently, returned to a chow diet. Cannulation of the pancreatic duct through a duodenal cutaneous fistula revealed the enzyme response to be decreased in a dog maintained with an elemental diet, with no or only a slight weight gain. Return to a regular diet resulted in a return of pancreatic enzyme response.", "contents": "Pancreatic enzyme response with an elemental diet. Elemental diets can maintain or slightly improve the nutritional status without a major stimulatory effect on the pancreas. Six dogs were maintained with a regular chow diet, switched to an elemental diet and, subsequently, returned to a chow diet. Cannulation of the pancreatic duct through a duodenal cutaneous fistula revealed the enzyme response to be decreased in a dog maintained with an elemental diet, with no or only a slight weight gain. Return to a regular diet resulted in a return of pancreatic enzyme response."}
{"id": "PMID:807", "title": "Gastric fibrinolysis.", "content": "Gastric juice from 15 normals, 20 patients with gastric ulcer and 14 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhage gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurence of plasmic could be demonstrated directly immunologically in the gastric juice. By comparsion of plasmin and trypsin in various assays it could further be improved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and alpha2-M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.", "contents": "Gastric fibrinolysis. Gastric juice from 15 normals, 20 patients with gastric ulcer and 14 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhage gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurence of plasmic could be demonstrated directly immunologically in the gastric juice. By comparsion of plasmin and trypsin in various assays it could further be improved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and alpha2-M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism."}
{"id": "PMID:814", "title": "Acid-base parameters in the dehydrated camel.", "content": "The effect of  prolonged (10 days) dehydration on acid-base parameters of camel blood was examined. The pH and PCO2 levels rose significantly in the course of dehydration. This state was comparable with compensated non-respiratory alkalosis found in other animals. The plasma sodium, and magnesium levels rose significantly also. The plasma oxygen and calcium levels declined significantly. There were no significant changes in potassium and phosphate levels. It is concluded that the changes found in acid-base status following dehydration are further evidence of water preservation mechanisms in the dehydrated camel.", "contents": "Acid-base parameters in the dehydrated camel. The effect of  prolonged (10 days) dehydration on acid-base parameters of camel blood was examined. The pH and PCO2 levels rose significantly in the course of dehydration. This state was comparable with compensated non-respiratory alkalosis found in other animals. The plasma sodium, and magnesium levels rose significantly also. The plasma oxygen and calcium levels declined significantly. There were no significant changes in potassium and phosphate levels. It is concluded that the changes found in acid-base status following dehydration are further evidence of water preservation mechanisms in the dehydrated camel."}
{"id": "PMID:815", "title": "[Clinical experiences with untreated homologous vein grafts in reconstruction of arteries (author's transl)].", "content": "50 transplantations of homologous vein grafts in reconstruction of arteries are reported on. Vein grafts were either transplanted immediately or used after deep freezing. This procedure has proved to be effective in the replacement of arteries during our observation period of four years. Results of homologous vein transplants are similar to those of autologous transplants.", "contents": "[Clinical experiences with untreated homologous vein grafts in reconstruction of arteries (author's transl)]. 50 transplantations of homologous vein grafts in reconstruction of arteries are reported on. Vein grafts were either transplanted immediately or used after deep freezing. This procedure has proved to be effective in the replacement of arteries during our observation period of four years. Results of homologous vein transplants are similar to those of autologous transplants."}
{"id": "PMID:820", "title": "The effect of a simulated subarachnoid hemorrhage on cerebral blood flow in the monkey.", "content": "The hydrogen clearance method was used to measure local and total cerebral blood flow (CBF) in the rhesus monkey before and for five hours after a simulated subarachnoid hemorrhage (SAH). CBF remained stable after SAH unless SAH was associated with a fall in cerebral perfusion pressure. In addition, cerebrovascular resistance did not increase after SAH. These results suggest that vasoactive agents in fresh whole blood, and the arterial spasm they produce when added to cerebrospinal fluid (CSF), play only a limited role in the pathogenesis of ischemic encephalopathy that follows an SAH.", "contents": "The effect of a simulated subarachnoid hemorrhage on cerebral blood flow in the monkey. The hydrogen clearance method was used to measure local and total cerebral blood flow (CBF) in the rhesus monkey before and for five hours after a simulated subarachnoid hemorrhage (SAH). CBF remained stable after SAH unless SAH was associated with a fall in cerebral perfusion pressure. In addition, cerebrovascular resistance did not increase after SAH. These results suggest that vasoactive agents in fresh whole blood, and the arterial spasm they produce when added to cerebrospinal fluid (CSF), play only a limited role in the pathogenesis of ischemic encephalopathy that follows an SAH."}
{"id": "PMID:821", "title": "Effects of oxygen saturation and pCO2 on brain uptake of glucose analogues in rabbits.", "content": "The effect of oxygen saturation and PCO2 on brain uptake of glucose analogues was studied in rabbits. Using a modified Oldendorf technique, 14C-labeled glucose analogues with a 3H2O reference standard were introduced into the cerebral circulation via the common carotid artery, and the radioactivity of the ipsilateral cerebral cortex was counted and expressed in terms of a brain uptake index (BUI). Severe hypoxia (oxygen saturation less than or equal to 18%) resulted in approximately a 40% decrease in the BUI of 2-deoxy-D-glucose and a 45% decrease in the BUI of 3-0-methyl-D-glucose. Severe hypercapnia (PCO2 = 100 mm Hg) caused a 45% decrease in the BUI of both of these glucose analogues. Hypercapnia superimposed on severe hypoxia had no additional effect. Hypocapnia (PCO2 = 15 mm Hg) increased the BUI of 3-0-methyl-D-glucose by 35% of the control value, and this increase was extremely sensitive to competitive inhibition. When BUI values were plotted against pH rather than PCO2 for the same experiments, there was a good correlation with the calculated linear regression. These results are compared with previous findings on pathologically induced changes in brain uptake of glucose analogues, and the possible role of blood flow is considered in detail.", "contents": "Effects of oxygen saturation and pCO2 on brain uptake of glucose analogues in rabbits. The effect of oxygen saturation and PCO2 on brain uptake of glucose analogues was studied in rabbits. Using a modified Oldendorf technique, 14C-labeled glucose analogues with a 3H2O reference standard were introduced into the cerebral circulation via the common carotid artery, and the radioactivity of the ipsilateral cerebral cortex was counted and expressed in terms of a brain uptake index (BUI). Severe hypoxia (oxygen saturation less than or equal to 18%) resulted in approximately a 40% decrease in the BUI of 2-deoxy-D-glucose and a 45% decrease in the BUI of 3-0-methyl-D-glucose. Severe hypercapnia (PCO2 = 100 mm Hg) caused a 45% decrease in the BUI of both of these glucose analogues. Hypercapnia superimposed on severe hypoxia had no additional effect. Hypocapnia (PCO2 = 15 mm Hg) increased the BUI of 3-0-methyl-D-glucose by 35% of the control value, and this increase was extremely sensitive to competitive inhibition. When BUI values were plotted against pH rather than PCO2 for the same experiments, there was a good correlation with the calculated linear regression. These results are compared with previous findings on pathologically induced changes in brain uptake of glucose analogues, and the possible role of blood flow is considered in detail."}
{"id": "PMID:825", "title": "Engraftment of allogeneic dog bone marrow.", "content": "Resistance to allogeneic bone-marrow grafts (AR) was found to occur in many species, including the dog. The i.v. administration of silica particles suppressed AR in vivo in this species. Genetic studies provide suggestive evidence for the existence of a previously unrecognized system or systems in the canine major histocompatibility complex controlling AR.", "contents": "Engraftment of allogeneic dog bone marrow. Resistance to allogeneic bone-marrow grafts (AR) was found to occur in many species, including the dog. The i.v. administration of silica particles suppressed AR in vivo in this species. Genetic studies provide suggestive evidence for the existence of a previously unrecognized system or systems in the canine major histocompatibility complex controlling AR."}
{"id": "PMID:822", "title": "Lactate and pyruvate concentrations, and acid-base balance of cerebrospinal fluid in experimentally induced intracerebral and subarachnoid hemorrhage in dogs.", "content": "The effect of blood injected into either subarachnoid space or subcortical brain tissue upon lactate and pyruvate concentrations as well as acid-base balance of cerebrospinal fluid (CSF) was studied in the anesthetized dog. CSF lactate and lactate/pyruvate ratio (L/P ratio) increased progressively following the intracranial injection of blood and reached the maximum level at six hours after injection. These changes were significantly greater in animals with intracerebral hematoma than in those with subarachnoid hemorrhage (SAH). An increase in CSF lactate and L/P ratio in hemorrhagic CSF seems to be caused by two different factors. Shed blood cells per se produce lactate and pyruvate, and blood in the subarachnoid space and intracerebral hematomas cause secondary changes in brain tissue metabolism by a probable reduction of cerebral blood flow. Therefore, an increase in CSF lactate with a concomitant rise in CSF L/P ratio is a useful indicator for brain tissue hypoxia, even when CSF is hemorrhagic. The association of an increase in CSF lactate to a disproportionate decrease in CSF HCO-3 was also observed in these animals.", "contents": "Lactate and pyruvate concentrations, and acid-base balance of cerebrospinal fluid in experimentally induced intracerebral and subarachnoid hemorrhage in dogs. The effect of blood injected into either subarachnoid space or subcortical brain tissue upon lactate and pyruvate concentrations as well as acid-base balance of cerebrospinal fluid (CSF) was studied in the anesthetized dog. CSF lactate and lactate/pyruvate ratio (L/P ratio) increased progressively following the intracranial injection of blood and reached the maximum level at six hours after injection. These changes were significantly greater in animals with intracerebral hematoma than in those with subarachnoid hemorrhage (SAH). An increase in CSF lactate and L/P ratio in hemorrhagic CSF seems to be caused by two different factors. Shed blood cells per se produce lactate and pyruvate, and blood in the subarachnoid space and intracerebral hematomas cause secondary changes in brain tissue metabolism by a probable reduction of cerebral blood flow. Therefore, an increase in CSF lactate with a concomitant rise in CSF L/P ratio is a useful indicator for brain tissue hypoxia, even when CSF is hemorrhagic. The association of an increase in CSF lactate to a disproportionate decrease in CSF HCO-3 was also observed in these animals."}
{"id": "PMID:823", "title": "A study of variables affecting the quality of platelets stored at \"room temperature\".", "content": "The effect of variables associated with the donor and with methods of collecting, processing, and storing platelets on the quality of platelets kept at ambient temperature was studied. Changes in structural integrity of platelets, decrease in pH, loss of aggregability, and kinetics in vivo of platelets tagged with 51Cr were used as indicators of the tolerance of platelets to storage. A platelet concentration of less than 2.5 x 10(6) per cu mm, a temperature of storage less than 24 C, and continuous, gentle, agitation were found to be essential for satisfactory preservation of platelet integrity, function, and post-transfusion survival. Platelets from female donors tolerated storage less well than did platelets from male donors, possibly because the lower hematocrit of blood collection from females resulted in greater initial acidity of the concentrate. A number of other variables analyzed appear to be of little or no consequence for successful platelet storage.", "contents": "A study of variables affecting the quality of platelets stored at \"room temperature\". The effect of variables associated with the donor and with methods of collecting, processing, and storing platelets on the quality of platelets kept at ambient temperature was studied. Changes in structural integrity of platelets, decrease in pH, loss of aggregability, and kinetics in vivo of platelets tagged with 51Cr were used as indicators of the tolerance of platelets to storage. A platelet concentration of less than 2.5 x 10(6) per cu mm, a temperature of storage less than 24 C, and continuous, gentle, agitation were found to be essential for satisfactory preservation of platelet integrity, function, and post-transfusion survival. Platelets from female donors tolerated storage less well than did platelets from male donors, possibly because the lower hematocrit of blood collection from females resulted in greater initial acidity of the concentrate. A number of other variables analyzed appear to be of little or no consequence for successful platelet storage."}
{"id": "PMID:827", "title": "Dopamine-containing neurons of the substantia nigra and their terminals in the neostriatum.", "content": "Tne ultrastructural and fluorescence histochemical characteristics of the mature rabbit substantia nigra and neostriatum have been reviewed as a frame of reference for the developmental study. Biochemical investigations were reported on neostriatal dopamine concentrations and the relative uptake and accumulation of 3H-dopamine by this tissue from fetal to adult stages, to provide quantitative data for correlation with the fluorexcence information. The development of the neurons of the substantia nigra and their axons which project to the neostriatum has been presented from their appearance at day 14 of gestation to their maturation in early postnatal life. The initial bipolar neuroblasts, which develop in the midline of the caudal mesencephalon, are fluorescent as soon as they emerge from the ependymal zone. Their fluorescent axons, which form the nigroneostriatal pathway, reach the telencephalon at day 16 of gestation and ramify extensively in the putamen by day 20, but do not enter the caudate nucleus until several days later. Some of the early fluorescent axonal profiles in the putamen are extremely large. Electron microscopic study of theis stage suggests that the large fluorescent profiles may correspond to axonal growth cones or early synapses. A distinct substantia nigra, pars compacta and reticulata, can be recognized by fluorescence microscopy by day 20 of gestation. Electron microscopy reveals that the young neurons are multipolar with numerous developing dendrites, some of which exhibit early synaptic junctions. The subsequent maturaition of these cells and the neuropil is described. The fluorescent axons of the substantia nigra grow into the putamen and caudate nucleus in a nonuniform manner forming fluorescent islands throughout the neostriatum in late fetal life. Occasionally, minute beaded fluorescent axons are found. These profiles might correspond to some of the axons with varicosities \"en passage\" revealed by electron microscopy. In an attempt to identify further the dopamine-containing axon, the ultratructure of adult neostriatum incubated in 5-hydroxydopamine was reported. Axonal varicosities \"en passage\" containing a dense \"tag\" in the vesicles were found. Most of the tagged boutons did not exhibit synaptic contacts. The possible significance of these finding s as related to dopamine secretion are discussed.", "contents": "Dopamine-containing neurons of the substantia nigra and their terminals in the neostriatum. Tne ultrastructural and fluorescence histochemical characteristics of the mature rabbit substantia nigra and neostriatum have been reviewed as a frame of reference for the developmental study. Biochemical investigations were reported on neostriatal dopamine concentrations and the relative uptake and accumulation of 3H-dopamine by this tissue from fetal to adult stages, to provide quantitative data for correlation with the fluorexcence information. The development of the neurons of the substantia nigra and their axons which project to the neostriatum has been presented from their appearance at day 14 of gestation to their maturation in early postnatal life. The initial bipolar neuroblasts, which develop in the midline of the caudal mesencephalon, are fluorescent as soon as they emerge from the ependymal zone. Their fluorescent axons, which form the nigroneostriatal pathway, reach the telencephalon at day 16 of gestation and ramify extensively in the putamen by day 20, but do not enter the caudate nucleus until several days later. Some of the early fluorescent axonal profiles in the putamen are extremely large. Electron microscopic study of theis stage suggests that the large fluorescent profiles may correspond to axonal growth cones or early synapses. A distinct substantia nigra, pars compacta and reticulata, can be recognized by fluorescence microscopy by day 20 of gestation. Electron microscopy reveals that the young neurons are multipolar with numerous developing dendrites, some of which exhibit early synaptic junctions. The subsequent maturaition of these cells and the neuropil is described. The fluorescent axons of the substantia nigra grow into the putamen and caudate nucleus in a nonuniform manner forming fluorescent islands throughout the neostriatum in late fetal life. Occasionally, minute beaded fluorescent axons are found. These profiles might correspond to some of the axons with varicosities \"en passage\" revealed by electron microscopy. In an attempt to identify further the dopamine-containing axon, the ultratructure of adult neostriatum incubated in 5-hydroxydopamine was reported. Axonal varicosities \"en passage\" containing a dense \"tag\" in the vesicles were found. Most of the tagged boutons did not exhibit synaptic contacts. The possible significance of these finding s as related to dopamine secretion are discussed."}
{"id": "PMID:829", "title": "[Separation of the hormones of the adenohypophysis of rats by use of electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate].", "content": "A comparative study of rat adenohypophysis extract and its alcohol fractions was performed by two variants of the method of electrophoresis in polyacrylamide gel: at pH 9,5 and with the presence of sodium dodecyl sulphate at pH 7.2. With the presence of sodium dodecylsulphate four protein zones are found which in the order from the anode towards the cathode are identified as hemoglobin, somatotropin, lactotropin and albumin. It is shown that the somatotropin zone after the extract separation at pH 9.5 is inhomogeneous and consists of somatotropin and hemoglobin.", "contents": "[Separation of the hormones of the adenohypophysis of rats by use of electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate]. A comparative study of rat adenohypophysis extract and its alcohol fractions was performed by two variants of the method of electrophoresis in polyacrylamide gel: at pH 9,5 and with the presence of sodium dodecyl sulphate at pH 7.2. With the presence of sodium dodecylsulphate four protein zones are found which in the order from the anode towards the cathode are identified as hemoglobin, somatotropin, lactotropin and albumin. It is shown that the somatotropin zone after the extract separation at pH 9.5 is inhomogeneous and consists of somatotropin and hemoglobin."}
{"id": "PMID:830", "title": "[Properties of NAD-glycohydrolase of the nuclei of the liver cells of rats].", "content": "Certain properties of the rat liver cell nuclei NAD-glycohydrolase (EC 3.2.2.5) were investigated. It is established that its highest activity is at 37 degrees with activation energy equal to 9480 cal/M and with factor Q10 equal to 1.5. The enzyme pH optimum in 0.2 M tris acetate is equal to 6.5 and in 0.2 potassium phosphate - 7.5. It was shown that the enzyme manifests its strict specificity only with beta-NAD, and it hardly decomposes NADP without affecting NADH, NADPH and NMN. The apparent Km value of the enzyme with respect to NAD is established. Isonicotinic acid hydrazide, nicotinamide and to the less extent nicotinic acid inhibit the enzymatic activity of nuclei. EDTA, EGTA, p-CMB, mercaptoethanol do not cause any changes in the rat liver cells nuclei NADase activity.", "contents": "[Properties of NAD-glycohydrolase of the nuclei of the liver cells of rats]. Certain properties of the rat liver cell nuclei NAD-glycohydrolase (EC 3.2.2.5) were investigated. It is established that its highest activity is at 37 degrees with activation energy equal to 9480 cal/M and with factor Q10 equal to 1.5. The enzyme pH optimum in 0.2 M tris acetate is equal to 6.5 and in 0.2 potassium phosphate - 7.5. It was shown that the enzyme manifests its strict specificity only with beta-NAD, and it hardly decomposes NADP without affecting NADH, NADPH and NMN. The apparent Km value of the enzyme with respect to NAD is established. Isonicotinic acid hydrazide, nicotinamide and to the less extent nicotinic acid inhibit the enzymatic activity of nuclei. EDTA, EGTA, p-CMB, mercaptoethanol do not cause any changes in the rat liver cells nuclei NADase activity."}
{"id": "PMID:831", "title": "[Some properties of \"soluble\" Na+ and K+-ATPase obtained from various subcellular membrane structures of the brain by use of non-ionic detergents].", "content": "A comparative study was carried out of some properties of \"soluble\" Na+, K+-ATPase obtained from different subcellular membrane brain structures by means of non-ionic detergents of triton X-100 and digitonin. It is established that temperature and pH-optima of \"soluble\" Na+, K+-ATPase are close to these optima of the initial membrane preparations. A certain difference is observed in the dynamics of temperature and pH-dependence of Na+, K+-ATPase activity in the extracts from different subcellular structures. The stability of the preparations in storage was investigated. A conclusion is made that more stable enzyme extracts may be obtained by means of digitonin.", "contents": "[Some properties of \"soluble\" Na+ and K+-ATPase obtained from various subcellular membrane structures of the brain by use of non-ionic detergents]. A comparative study was carried out of some properties of \"soluble\" Na+, K+-ATPase obtained from different subcellular membrane brain structures by means of non-ionic detergents of triton X-100 and digitonin. It is established that temperature and pH-optima of \"soluble\" Na+, K+-ATPase are close to these optima of the initial membrane preparations. A certain difference is observed in the dynamics of temperature and pH-dependence of Na+, K+-ATPase activity in the extracts from different subcellular structures. The stability of the preparations in storage was investigated. A conclusion is made that more stable enzyme extracts may be obtained by means of digitonin."}
{"id": "PMID:832", "title": "[Properties of glutamine synthetase of the brain of rats during ontogenesis].", "content": "When investigating activity of glutamine synthetase of the enzymatic preparations isolated from the brain of rats of 0.5, 1, 3, 12 and 24-month age, no considerable differences were found in the indices of the values Km to a-glutamate and Vmax which are respectively equal to: Km (M-10(-3))=5.5; 3.5; 3.6; 3.9; 5.5; Vmax=3.1; 4.5; 5.0; 5.2 muM were found. When adding various concentrations of a-ketoglutaric acid into the incubation medium the differences are registered in the degree and character of the age changes in brain glutamine synthetase activity in comparison with this enzyme form the liver.", "contents": "[Properties of glutamine synthetase of the brain of rats during ontogenesis]. When investigating activity of glutamine synthetase of the enzymatic preparations isolated from the brain of rats of 0.5, 1, 3, 12 and 24-month age, no considerable differences were found in the indices of the values Km to a-glutamate and Vmax which are respectively equal to: Km (M-10(-3))=5.5; 3.5; 3.6; 3.9; 5.5; Vmax=3.1; 4.5; 5.0; 5.2 muM were found. When adding various concentrations of a-ketoglutaric acid into the incubation medium the differences are registered in the degree and character of the age changes in brain glutamine synthetase activity in comparison with this enzyme form the liver."}
{"id": "PMID:834", "title": "[Biosynthesis of flavins and its regulation in the yeast Pichia guilliermondii].", "content": "The nature of riboflavin precursors was studied in the yeast Pichia guilliermondii. By means of mutants with blocked GMP-synthetase the purine precursors of riboflavin were shown to belong to guanylic compounds. Accumulation of 2,4,5-triamino-6-oxypyrimidine, 2,5-diamino-6-oxy-4-ribitylaminopyrimidine, 2,6-dioxy-5-amino-4-ribitylaminopyrimidine (DOARAP) and 6,7-dimethyl-8-ribityllumasine occurs in the riboflavin-deficient mutants divided into five biochemical groups. This fact evidences for identity of riboflavin precursors in the yeast P. guilliermondii and Saccharomyces cerevisiae. Synthesis of DOARAP by the washed off cells of the mutants with the blocked lumasine synthetase is strongly inhibited by riboflavin; cycloheximide in the absence of riboflavin has no effect on this process. Consequently, flavinogenesis in P. guilliermondii is regulated according to the type of negative feedback by means of retroinhibition mechanism. A change in the content of flavins in the cells has no effect on synthesis of riboflavin synthetase; at the same time iron deficiency in the cells evokes derepression of this enzyme. Incubation of the cells rich in iron with o-phenantroline or alpha, alpha'-dipyridyl also causes derepression of riboflavin synthetase which is inhibited by cycloheximide. A deficiency of hem in the mutants which need epsilon-aminolevulinic acid does not affect the riboflavinsynthetase activity of the cells. Evidently, in P. guilliermondii a certain form of nonheminic iron might take part in regulating synthesis of riboflavin synthetase and other enzymes participating in riboflavin biosynthesis. Riboflavin overproduction is established to require formation of purines de novo. With the absence of flavinogenesis enzymes derepression a genetic disturbance in regulation of purinic nucleotides biosynthesis results in stimulation of flavinogenesis. The properties were studied for 680 time purified riboflavinkinase from cells of P. guilliermondii as well as for three phosphatases possessing the optimum of the activity at pH 3.5, 5.5 and 8.6, which ARE ABLE OF HYDROLYSING FMN. A change in the content of flavins and iron in the cells has no effect on the activity of riboflavinkinase in this species. Evidently, the mechanisms of riboflavin and flavin nucleotides biosynthesis regulation would be different in P. guilliermondii.", "contents": "[Biosynthesis of flavins and its regulation in the yeast Pichia guilliermondii]. The nature of riboflavin precursors was studied in the yeast Pichia guilliermondii. By means of mutants with blocked GMP-synthetase the purine precursors of riboflavin were shown to belong to guanylic compounds. Accumulation of 2,4,5-triamino-6-oxypyrimidine, 2,5-diamino-6-oxy-4-ribitylaminopyrimidine, 2,6-dioxy-5-amino-4-ribitylaminopyrimidine (DOARAP) and 6,7-dimethyl-8-ribityllumasine occurs in the riboflavin-deficient mutants divided into five biochemical groups. This fact evidences for identity of riboflavin precursors in the yeast P. guilliermondii and Saccharomyces cerevisiae. Synthesis of DOARAP by the washed off cells of the mutants with the blocked lumasine synthetase is strongly inhibited by riboflavin; cycloheximide in the absence of riboflavin has no effect on this process. Consequently, flavinogenesis in P. guilliermondii is regulated according to the type of negative feedback by means of retroinhibition mechanism. A change in the content of flavins in the cells has no effect on synthesis of riboflavin synthetase; at the same time iron deficiency in the cells evokes derepression of this enzyme. Incubation of the cells rich in iron with o-phenantroline or alpha, alpha'-dipyridyl also causes derepression of riboflavin synthetase which is inhibited by cycloheximide. A deficiency of hem in the mutants which need epsilon-aminolevulinic acid does not affect the riboflavinsynthetase activity of the cells. Evidently, in P. guilliermondii a certain form of nonheminic iron might take part in regulating synthesis of riboflavin synthetase and other enzymes participating in riboflavin biosynthesis. Riboflavin overproduction is established to require formation of purines de novo. With the absence of flavinogenesis enzymes derepression a genetic disturbance in regulation of purinic nucleotides biosynthesis results in stimulation of flavinogenesis. The properties were studied for 680 time purified riboflavinkinase from cells of P. guilliermondii as well as for three phosphatases possessing the optimum of the activity at pH 3.5, 5.5 and 8.6, which ARE ABLE OF HYDROLYSING FMN. A change in the content of flavins and iron in the cells has no effect on the activity of riboflavinkinase in this species. Evidently, the mechanisms of riboflavin and flavin nucleotides biosynthesis regulation would be different in P. guilliermondii."}
{"id": "PMID:835", "title": "[DNases and RNases of Misgurnus fossilis ovocytes].", "content": "The pH optima were determined for DNases and RNases of the loach eggs. For DNases they are 5.6 and 7.6 and for RNases - 5.2 and 7.2. It is established that Ca++ activates, and Fe++ has not effect on the activity of acid and alkaline DNases, while Mg++, Mn++ and especially Co++, Zn++, Cd++, Cu++ have an inhibitory effect on them. The activities of RNases is stimulated by Ca++ and Fe++, and inhibited by Zn++, Co++, Cd++ and Cu++. Iones Mg++ and Mn++ do not affect these activities. Localization of the above mentioned enzymes was studied by means of differential centrifugation of egg homogenates. Acid DNase is concentrated only in postmicrosomal supernatant liquid, its activity being inhibited in the presence of the nucleomitochondrial and microsomal fractions. Acid RNase is also localized predominantly in postmicrosomal supernatant fraction. Alkaline DNase is found to a great extent in nucleomitochondrial fraction, and alkaline RNase - in postmicrosomal one.", "contents": "[DNases and RNases of Misgurnus fossilis ovocytes]. The pH optima were determined for DNases and RNases of the loach eggs. For DNases they are 5.6 and 7.6 and for RNases - 5.2 and 7.2. It is established that Ca++ activates, and Fe++ has not effect on the activity of acid and alkaline DNases, while Mg++, Mn++ and especially Co++, Zn++, Cd++, Cu++ have an inhibitory effect on them. The activities of RNases is stimulated by Ca++ and Fe++, and inhibited by Zn++, Co++, Cd++ and Cu++. Iones Mg++ and Mn++ do not affect these activities. Localization of the above mentioned enzymes was studied by means of differential centrifugation of egg homogenates. Acid DNase is concentrated only in postmicrosomal supernatant liquid, its activity being inhibited in the presence of the nucleomitochondrial and microsomal fractions. Acid RNase is also localized predominantly in postmicrosomal supernatant fraction. Alkaline DNase is found to a great extent in nucleomitochondrial fraction, and alkaline RNase - in postmicrosomal one."}
{"id": "PMID:833", "title": "[Properties of NAD-pyrophosphorylase of the nuclei of liver cells of chickens].", "content": "Certain characteristics of chicken liver cells nuclei NAD-pyrophosphorylase (NMN-adenylytranspherase, EC 2.7.7.1) were investigated. It was established that NAD-pyrophosphorylase activity optimum pH is within interval of 7.0-7.5; temperature optimum - 38-39 degrees C; factor Q10 is equal to 2. Enzyme activation energy, inactivation energy and enthalpy were calculated; apparent Km values of NAD-pyrophosphorylase with respect to NMN and ATP are equal to 1.62-10(-7) M and 2.61-10(-7) M, respectively.", "contents": "[Properties of NAD-pyrophosphorylase of the nuclei of liver cells of chickens]. Certain characteristics of chicken liver cells nuclei NAD-pyrophosphorylase (NMN-adenylytranspherase, EC 2.7.7.1) were investigated. It was established that NAD-pyrophosphorylase activity optimum pH is within interval of 7.0-7.5; temperature optimum - 38-39 degrees C; factor Q10 is equal to 2. Enzyme activation energy, inactivation energy and enthalpy were calculated; apparent Km values of NAD-pyrophosphorylase with respect to NMN and ATP are equal to 1.62-10(-7) M and 2.61-10(-7) M, respectively."}
{"id": "PMID:839", "title": "[Catecholamines, cholinergic and serotoninergic complexes as criteria of prognosis in acute cranio-cerebral trauma].", "content": "In experiments on 30 animals and in observations over the course of acute closed craniocerebral trauma in 24 patients is was found that the course and prognosis of a posttraumatic period were dependent on the functional activity of the sympathoadrenal system and cholin- and serotoninergic processes. Based on the data obtained, it is concluded that the character of neurohumoral interrelations can serve as the prognostic criterion in craniocerebral traumas, whereas the information about these processes--in selecting the appropriate therapy.", "contents": "[Catecholamines, cholinergic and serotoninergic complexes as criteria of prognosis in acute cranio-cerebral trauma]. In experiments on 30 animals and in observations over the course of acute closed craniocerebral trauma in 24 patients is was found that the course and prognosis of a posttraumatic period were dependent on the functional activity of the sympathoadrenal system and cholin- and serotoninergic processes. Based on the data obtained, it is concluded that the character of neurohumoral interrelations can serve as the prognostic criterion in craniocerebral traumas, whereas the information about these processes--in selecting the appropriate therapy."}
{"id": "PMID:840", "title": "[Incarcerated gallbladder in cholecystitis].", "content": "Among 206 examined patients with cholecystitis and similar diseases in 112 (65%) cases, as evidenced by the authors' findings, the gallbladder proved to be non-functioning. Its escape in the biliary system was functional (indirect) or organic (absolute). The main causes of a direct organic escape of the gallbladder are as follows: destructive changes in its walls, strictures, strangulated gall stones, shrinkage or hydropsy. The reliable preoperative diagnosis of an escaped gallbladder by means of accelerated chromoduodenal catheterization, intravenous (infusion-drip) or associated (intravenous-peroral) cholecystocholangiography, correlated with the anamnesis data and clinical signs, rather speaks in favour of cholecystectomy on absolute indications.", "contents": "[Incarcerated gallbladder in cholecystitis]. Among 206 examined patients with cholecystitis and similar diseases in 112 (65%) cases, as evidenced by the authors' findings, the gallbladder proved to be non-functioning. Its escape in the biliary system was functional (indirect) or organic (absolute). The main causes of a direct organic escape of the gallbladder are as follows: destructive changes in its walls, strictures, strangulated gall stones, shrinkage or hydropsy. The reliable preoperative diagnosis of an escaped gallbladder by means of accelerated chromoduodenal catheterization, intravenous (infusion-drip) or associated (intravenous-peroral) cholecystocholangiography, correlated with the anamnesis data and clinical signs, rather speaks in favour of cholecystectomy on absolute indications."}
{"id": "PMID:836", "title": "[Determination of optimal conditions for the electron-cytochemical detection of ATPase activity in isolated nuclei].", "content": "The optimal conditions are selected for electron-cytochemical detection of the ATPase activity in nuclei of the skeletal muscles of rabbits and nuclei of Vicia faba L. meristem. It is shown that the previous fixation of nuclei in the rabbit skeletal muscle for 10 min in a mixture of the buffer solutions of 4% glutaric dialdehyde and 4% neutral formalin (1:1) causes a decrease in their ATPase activity by 78% in the medium containing Mg2+ and by 34% - in the medium containing Ca2+; in nuclei of horse bean seedlings meristem it lowers respectively by 28 and 16%. Ions of lead in a concentration of 0.4 mM evoke a decrease in the ATPase activity in the medium containing Mg2+, in nuclei of the rabbit skeletal muscles by 35% and in nuclei of horse bean meristem by 15% in the medium containing Ca2+. The vaule of the residual activity is sufficient for detection of the product of ATP enzymic hydrolysis reaction by activity is sufficient for detection of the product of ATP enzymic hydrolysis reaction by the method of electronic cytochemistry. An increase in the Pb2+ concentration higher than 2.8 mM evokes nonenzymic hydrolysis of ATP. The ATPase activity under the electron-cytochemical study is found within the range of pH 6.3-8.5. The product of reaction forms most intensively at pH 7.2-7.5 in the medium with both Mg2+ and Ca2+.", "contents": "[Determination of optimal conditions for the electron-cytochemical detection of ATPase activity in isolated nuclei]. The optimal conditions are selected for electron-cytochemical detection of the ATPase activity in nuclei of the skeletal muscles of rabbits and nuclei of Vicia faba L. meristem. It is shown that the previous fixation of nuclei in the rabbit skeletal muscle for 10 min in a mixture of the buffer solutions of 4% glutaric dialdehyde and 4% neutral formalin (1:1) causes a decrease in their ATPase activity by 78% in the medium containing Mg2+ and by 34% - in the medium containing Ca2+; in nuclei of horse bean seedlings meristem it lowers respectively by 28 and 16%. Ions of lead in a concentration of 0.4 mM evoke a decrease in the ATPase activity in the medium containing Mg2+, in nuclei of the rabbit skeletal muscles by 35% and in nuclei of horse bean meristem by 15% in the medium containing Ca2+. The vaule of the residual activity is sufficient for detection of the product of ATP enzymic hydrolysis reaction by activity is sufficient for detection of the product of ATP enzymic hydrolysis reaction by the method of electronic cytochemistry. An increase in the Pb2+ concentration higher than 2.8 mM evokes nonenzymic hydrolysis of ATP. The ATPase activity under the electron-cytochemical study is found within the range of pH 6.3-8.5. The product of reaction forms most intensively at pH 7.2-7.5 in the medium with both Mg2+ and Ca2+."}
{"id": "PMID:841", "title": "[Determination of the proteolytic activity of beef liver by means of natural substrates labed with 125 I].", "content": "There is a description of the determination of the enzymatic activity of acid proteinases: the method is based on the use of 125J-labelled natural protein substrates. Labelled albumin 125J, globulin 125J, and insulin 125J were tested for the determination of activities. All the substrates were hydrolyzed with the enzymes of the supernatant fraction (106 000 g) of beff liver homogenate in the zone of acid pH. Optimum comditions of enzymatic reaction were tested, the dependence of reaction on the concentration of the enzyme, on time, and on temperature was determined, pH optimum was ascertained for individual substrates, and pH stability was determined. It follows from the results that the method is suitable for the determination of the enzymatic activity of proteinases of the cathepsin character.", "contents": "[Determination of the proteolytic activity of beef liver by means of natural substrates labed with 125 I]. There is a description of the determination of the enzymatic activity of acid proteinases: the method is based on the use of 125J-labelled natural protein substrates. Labelled albumin 125J, globulin 125J, and insulin 125J were tested for the determination of activities. All the substrates were hydrolyzed with the enzymes of the supernatant fraction (106 000 g) of beff liver homogenate in the zone of acid pH. Optimum comditions of enzymatic reaction were tested, the dependence of reaction on the concentration of the enzyme, on time, and on temperature was determined, pH optimum was ascertained for individual substrates, and pH stability was determined. It follows from the results that the method is suitable for the determination of the enzymatic activity of proteinases of the cathepsin character."}
{"id": "PMID:842", "title": "Significance of serum pepsinogen and abomasal pH levels in a field infection of O circumcincta in lambs.", "content": "Serum pepsinogen  estimations from serially bled lambs grazing on pasture from spring to autumn showed correlations with the availability of Ostertagia larvae on pasture, with faecal egg counts of O circumcincta, and with Ostertagia worm counts in similar lambs slaughtered fort-nightly from the same pasture. In the slaughtered lambs correlations were recorded between worm count, serum pepsinogen level and abomasal pH. The value of serum pepsinogen estimations as a diagnostic test is discussed with reference to these findings.", "contents": "Significance of serum pepsinogen and abomasal pH levels in a field infection of O circumcincta in lambs. Serum pepsinogen  estimations from serially bled lambs grazing on pasture from spring to autumn showed correlations with the availability of Ostertagia larvae on pasture, with faecal egg counts of O circumcincta, and with Ostertagia worm counts in similar lambs slaughtered fort-nightly from the same pasture. In the slaughtered lambs correlations were recorded between worm count, serum pepsinogen level and abomasal pH. The value of serum pepsinogen estimations as a diagnostic test is discussed with reference to these findings."}
{"id": "PMID:843", "title": "[Cultivation of Trichomonas gallinarum and Trichomonas tenax on a trimed medium].", "content": "Studied was the possibility to isolate and culture Tr. gallinarum and Tr. tenax on a medium Trimed, proposed by the authors for the isolation and cultivation of Tr. vaginalis. The growth and development of the two Trichomonas species were followed up at various temperatures -- 38 degrees, 36 degrees, and 32 degrees C, in order to establish the most appropriate temperature for continuous cultivation at longer intervals of reseeding as well as the temperature optimum for the fast deposition of great amounts of biomass. It was found that the Trimed medium is suitable for the isolation and cultivation of Tr. gallinarum and Tr. tenax. Temperatures of 38 degrees and 36 degrees contribute to the accumulation of greater amounts of biomass, while at 32 degrees C the growth of these protozoa is delayed and reseeding is to be carried out at greater intervals.", "contents": "[Cultivation of Trichomonas gallinarum and Trichomonas tenax on a trimed medium]. Studied was the possibility to isolate and culture Tr. gallinarum and Tr. tenax on a medium Trimed, proposed by the authors for the isolation and cultivation of Tr. vaginalis. The growth and development of the two Trichomonas species were followed up at various temperatures -- 38 degrees, 36 degrees, and 32 degrees C, in order to establish the most appropriate temperature for continuous cultivation at longer intervals of reseeding as well as the temperature optimum for the fast deposition of great amounts of biomass. It was found that the Trimed medium is suitable for the isolation and cultivation of Tr. gallinarum and Tr. tenax. Temperatures of 38 degrees and 36 degrees contribute to the accumulation of greater amounts of biomass, while at 32 degrees C the growth of these protozoa is delayed and reseeding is to be carried out at greater intervals."}
{"id": "PMID:848", "title": "Amylase of the thermophilic actinomycete Thermomonospora vulgaris.", "content": "alpha-Amylase of the thermophilic actinomycete Thermomonospora vulgaris was partially purified. Maximal enzyme activity was obtained at 60degreeC and pH 6.0. KM value was l.4%. The effect of some metal salts on enzyme activity was studied. Enzyme activity was inhibited by by KCN, EDTA, and iodoacetate. Inhibition by EDTA was completely nullified by CaCl2, but the inhibition by iodoacetate was not overcome by 2-mercaptoethanol. Exposure of the enzyme to pH 7.0 and 9.0 for 2 hr. did not affect the enzyme, but exposure to pH 3.0 for few minutes completely inactivated the enzyme. Exposure of the enzyme to 60degreeC resulted in an appreciable inactivation and exposure to 80degreeC completely inactivated the enzyme. Addition of CaCl2, 2-mercaptoethanol, or enzyme substrate the 60degreeC exposed enzyme. However, bovine serym albumin had a protective effect when the enzyme was exposed to 60degreeC but not to 80degreeC. The enzyme was stable in the presence of 8 M urea.", "contents": "Amylase of the thermophilic actinomycete Thermomonospora vulgaris. alpha-Amylase of the thermophilic actinomycete Thermomonospora vulgaris was partially purified. Maximal enzyme activity was obtained at 60degreeC and pH 6.0. KM value was l.4%. The effect of some metal salts on enzyme activity was studied. Enzyme activity was inhibited by by KCN, EDTA, and iodoacetate. Inhibition by EDTA was completely nullified by CaCl2, but the inhibition by iodoacetate was not overcome by 2-mercaptoethanol. Exposure of the enzyme to pH 7.0 and 9.0 for 2 hr. did not affect the enzyme, but exposure to pH 3.0 for few minutes completely inactivated the enzyme. Exposure of the enzyme to 60degreeC resulted in an appreciable inactivation and exposure to 80degreeC completely inactivated the enzyme. Addition of CaCl2, 2-mercaptoethanol, or enzyme substrate the 60degreeC exposed enzyme. However, bovine serym albumin had a protective effect when the enzyme was exposed to 60degreeC but not to 80degreeC. The enzyme was stable in the presence of 8 M urea."}
{"id": "PMID:856", "title": "[The effect of therapeutic gentamycin doses on the enzyme secretion in urine].", "content": "8 patients with chronic pyelonephritis were given gentamycin intramuscularly injected in individual dosage during 8-10 days. Here the behaviour of the excretion of protein, alanine aminopeptidase alkaline phosphatase, alpha-glucosidase, gamma-glutamyl transpeptidase and lysozyme with the urine was tested. With the exception of the lysozymuria, which increased only in patients with chronic renal insufficiency, regularly a hyperenzymuria developed. Most distinctly the excretion of the alanine aminopeptidase increased. After initial decrease the excretion of total protein transiently increased after completion of the gentamycin therapy. All the deviations were reversible. From the increased excretion of enzymes may not be concluded to a nephrotoxicity of gentamycin.", "contents": "[The effect of therapeutic gentamycin doses on the enzyme secretion in urine]. 8 patients with chronic pyelonephritis were given gentamycin intramuscularly injected in individual dosage during 8-10 days. Here the behaviour of the excretion of protein, alanine aminopeptidase alkaline phosphatase, alpha-glucosidase, gamma-glutamyl transpeptidase and lysozyme with the urine was tested. With the exception of the lysozymuria, which increased only in patients with chronic renal insufficiency, regularly a hyperenzymuria developed. Most distinctly the excretion of the alanine aminopeptidase increased. After initial decrease the excretion of total protein transiently increased after completion of the gentamycin therapy. All the deviations were reversible. From the increased excretion of enzymes may not be concluded to a nephrotoxicity of gentamycin."}
{"id": "PMID:858", "title": "[Alkaline phosphatases in human feces, intestinal mucosa and bile, and the occurrence of 5'-nucleotidase in feces (author's transl)].", "content": "Alkaline phosphatase (EC 3.1.3.1) in extracts of human feces resembles alkaline phosphatase in extracts of duodenal mucosa, except for its electrophoretic mobility in starch gel. It is very probable that the normal feces alkaline phosphatase derives from intestinal mucosa. Gall bladder alkaline phosphatase, which is markedly different, has not been found in normal feces. Some patients with acute viral hepatitis or protozoasis excrete an alkaline phosphatase which resembles gall bladder alkaline phosphatase and has the characteristics of 5'-nucleotidase (EC 3.1.3.5). The appearance of this enzyme correlates with low total alkaline phosphatase activity of the excreta.", "contents": "[Alkaline phosphatases in human feces, intestinal mucosa and bile, and the occurrence of 5'-nucleotidase in feces (author's transl)]. Alkaline phosphatase (EC 3.1.3.1) in extracts of human feces resembles alkaline phosphatase in extracts of duodenal mucosa, except for its electrophoretic mobility in starch gel. It is very probable that the normal feces alkaline phosphatase derives from intestinal mucosa. Gall bladder alkaline phosphatase, which is markedly different, has not been found in normal feces. Some patients with acute viral hepatitis or protozoasis excrete an alkaline phosphatase which resembles gall bladder alkaline phosphatase and has the characteristics of 5'-nucleotidase (EC 3.1.3.5). The appearance of this enzyme correlates with low total alkaline phosphatase activity of the excreta."}
{"id": "PMID:859", "title": "Simultaneous determination of 5'-nucleotidase and alkaline phosphatase activities in serum.", "content": "A simple method is described for the simultaneous determination of alkaline phosphatase (EC 3.1.3.1) and 5'-nucleotidase (EC 3.1.3.5) in serum. The method is based on the determination of inorganic phosphorus released by the action of the two enzymes on adenosine-5'-monophosphate at pH 9.5 (200 mmol/l tris-buffer) in the presence and absence of L-cysteine. This amino acid at a concentration of 2--10 mmol/l was found to be a specific inhibitor for alkaline phosphatase but with no effect on 5'-nucleotidase activity.", "contents": "Simultaneous determination of 5'-nucleotidase and alkaline phosphatase activities in serum. A simple method is described for the simultaneous determination of alkaline phosphatase (EC 3.1.3.1) and 5'-nucleotidase (EC 3.1.3.5) in serum. The method is based on the determination of inorganic phosphorus released by the action of the two enzymes on adenosine-5'-monophosphate at pH 9.5 (200 mmol/l tris-buffer) in the presence and absence of L-cysteine. This amino acid at a concentration of 2--10 mmol/l was found to be a specific inhibitor for alkaline phosphatase but with no effect on 5'-nucleotidase activity."}
{"id": "PMID:860", "title": "Absorption of short and medium chain fatty acids in the jejunum of the rat.", "content": "The uptake of the shortest six fatty acids (acetic to octanoic) was studied in vitro, using everted segments of rat jejunum. The marked influence of medium-pH and fatty acid chain-length suggests that non-ionic diffusion through the lipoid membrane is quantitatively the most important way of transport, but ionic diffusion through the membrane as well as transport through hydrophilic pores also seem to play a role. Though fatt acids evidently are accumulated in the tissue-fluid, and saturation kinetics, competitive inhibition and sodium- as well as energy-dependence apparently are observed, the transport mechanism is assumed to involve solely passive diffusion, - the concept of a carrier-mediated transport for short and medium chain fatty acids seems improbable.", "contents": "Absorption of short and medium chain fatty acids in the jejunum of the rat. The uptake of the shortest six fatty acids (acetic to octanoic) was studied in vitro, using everted segments of rat jejunum. The marked influence of medium-pH and fatty acid chain-length suggests that non-ionic diffusion through the lipoid membrane is quantitatively the most important way of transport, but ionic diffusion through the membrane as well as transport through hydrophilic pores also seem to play a role. Though fatt acids evidently are accumulated in the tissue-fluid, and saturation kinetics, competitive inhibition and sodium- as well as energy-dependence apparently are observed, the transport mechanism is assumed to involve solely passive diffusion, - the concept of a carrier-mediated transport for short and medium chain fatty acids seems improbable."}
{"id": "PMID:861", "title": "Carcinogenic N-nitro-dimethylamine from the reaction of the analgesic amidopyrine and nitrite extracted from foodstuffs.", "content": "The reaction of the analgesic amidopyrine (100 mg) with nitrite extracted from cured meats and from spinach in varying degrees of spoilage was studied. Unde physiological conditions the carcinogenic dimethylnitrosamine was formed at milligram levels at nitrite concentrations as low as 4 mg (in 175 ml extracted from 100 g boiled ham). The rate of decrease in concentration in the human stomach after ingestion of amidopyrine and of nitrite contained in boiled ham or in a broth from boiled ham was also measured.", "contents": "Carcinogenic N-nitro-dimethylamine from the reaction of the analgesic amidopyrine and nitrite extracted from foodstuffs. The reaction of the analgesic amidopyrine (100 mg) with nitrite extracted from cured meats and from spinach in varying degrees of spoilage was studied. Unde physiological conditions the carcinogenic dimethylnitrosamine was formed at milligram levels at nitrite concentrations as low as 4 mg (in 175 ml extracted from 100 g boiled ham). The rate of decrease in concentration in the human stomach after ingestion of amidopyrine and of nitrite contained in boiled ham or in a broth from boiled ham was also measured."}
{"id": "PMID:863", "title": "[A modern quick method for the acidity determination of the gastric juice (pentagastrin test)].", "content": "The author describes a very rapid and accurate method of determining the acidity of gastric juice which is based on recent findings. Starting from the electrometrically determined pH value and the volume of the gastric juice, the actual hydrogenion concentration may be read from a table. The laboratory work is considerably simplified by this method.", "contents": "[A modern quick method for the acidity determination of the gastric juice (pentagastrin test)]. The author describes a very rapid and accurate method of determining the acidity of gastric juice which is based on recent findings. Starting from the electrometrically determined pH value and the volume of the gastric juice, the actual hydrogenion concentration may be read from a table. The laboratory work is considerably simplified by this method."}
{"id": "PMID:864", "title": "Histochemical observations on the occurrence of glycolytic and pentose phosphate cycle enzymes in the hepatopancreas and their possible relation to eyestalk factor(s) in the crab Scylla serrata (Forskal).", "content": "Histochemical studies were carried out on some of the glycolytic enzymes viz. phosphorylase, aldose, alpha-glycerophosphate dehydrogenase (alpha-GPDH) and lactic dehydrogenase (LDH) and a key enzyme of the pentose phosphatase cycle, glucose-6-phosphate dehydrogenase (G-6-PDH), in the hepatopancreas of Scylla serrata (Forskal). 1. Weak activities of phosphorylase and aldolase and strong-activities of alpha-GPDH and LDH were noticed mainly in the brush border of the tubules and R-cell cytoplasm. A trace activity of G-6-PDH was noticed in the brush border. 2. Bilateral eyestalk removal results in inhibition of both phosphorylase and aldolase. However, enhanced activities of alpha-GPDH and LDH were noticeable 4 h after the operation. The G-6-PDH activity remained unaltered till 24 h. 3. Injection of eyestalk extract into both intact and destalked crabs activated all the enzymes.", "contents": "Histochemical observations on the occurrence of glycolytic and pentose phosphate cycle enzymes in the hepatopancreas and their possible relation to eyestalk factor(s) in the crab Scylla serrata (Forskal). Histochemical studies were carried out on some of the glycolytic enzymes viz. phosphorylase, aldose, alpha-glycerophosphate dehydrogenase (alpha-GPDH) and lactic dehydrogenase (LDH) and a key enzyme of the pentose phosphatase cycle, glucose-6-phosphate dehydrogenase (G-6-PDH), in the hepatopancreas of Scylla serrata (Forskal). 1. Weak activities of phosphorylase and aldolase and strong-activities of alpha-GPDH and LDH were noticed mainly in the brush border of the tubules and R-cell cytoplasm. A trace activity of G-6-PDH was noticed in the brush border. 2. Bilateral eyestalk removal results in inhibition of both phosphorylase and aldolase. However, enhanced activities of alpha-GPDH and LDH were noticeable 4 h after the operation. The G-6-PDH activity remained unaltered till 24 h. 3. Injection of eyestalk extract into both intact and destalked crabs activated all the enzymes."}
{"id": "PMID:872", "title": "[Acid-base equilibrium during physiological pregnancy].", "content": "Authors applied blood-gas analysis in 30 healthy gravid women on 3,3 occassions making out 90 cases altogether by blood samples taken from the pulp of the finger capillaries. As a control 27 healthy non-gravid women were examined for comparative analysis. In 10 cases between the 16. and 28. week the results of samples taken from the arteria femoralis and the pulp were evaluated. It has been found that in the gravidity period of the 16. and 28. week respiratory alcalosis does not appear. No metabolic changes have been found during the whole period of pregnancy. The parallel examination of blood samples taken from the arteria femoralis and the pulp have proved that it is sufficient and reliable to take blood-gas analysis on the material gained from the pulp capillary only. A special importance is attached to keeping to exact methodical prescriptions.", "contents": "[Acid-base equilibrium during physiological pregnancy]. Authors applied blood-gas analysis in 30 healthy gravid women on 3,3 occassions making out 90 cases altogether by blood samples taken from the pulp of the finger capillaries. As a control 27 healthy non-gravid women were examined for comparative analysis. In 10 cases between the 16. and 28. week the results of samples taken from the arteria femoralis and the pulp were evaluated. It has been found that in the gravidity period of the 16. and 28. week respiratory alcalosis does not appear. No metabolic changes have been found during the whole period of pregnancy. The parallel examination of blood samples taken from the arteria femoralis and the pulp have proved that it is sufficient and reliable to take blood-gas analysis on the material gained from the pulp capillary only. A special importance is attached to keeping to exact methodical prescriptions."}
{"id": "PMID:873", "title": "[The cathode bound group antigen of dysentery-provoking escherichieae (author's transl)].", "content": "Antigens from disrupted cells of dysentery-provoking and of non-enteropathogenic Escherichieae were submitted to immunoelectrophoresis on cellulose acetate stripes at pH 8.0. Among 6 immune sera produced for this purpose by immunizing rabbits against desintegrated dysentery bacteria, only one contained a precipitine reacting with an antigen similar to the \"generic antigen\" of BELAYA. This - at pH 8.0 - cathode-bound group antigen (KGA) could not only be found in virulent but also in 5 attenuated cultures and in 5 from 6 avirulent strains of several dysentery types. Only the - apathogenic - type culture 1111/55 of dysentery-provoking E. coli O 136 showed no KGA-reaction. Some sources of methodical errors responsible for false outcomes of immunopherogrammes have been discussed.", "contents": "[The cathode bound group antigen of dysentery-provoking escherichieae (author's transl)]. Antigens from disrupted cells of dysentery-provoking and of non-enteropathogenic Escherichieae were submitted to immunoelectrophoresis on cellulose acetate stripes at pH 8.0. Among 6 immune sera produced for this purpose by immunizing rabbits against desintegrated dysentery bacteria, only one contained a precipitine reacting with an antigen similar to the \"generic antigen\" of BELAYA. This - at pH 8.0 - cathode-bound group antigen (KGA) could not only be found in virulent but also in 5 attenuated cultures and in 5 from 6 avirulent strains of several dysentery types. Only the - apathogenic - type culture 1111/55 of dysentery-provoking E. coli O 136 showed no KGA-reaction. Some sources of methodical errors responsible for false outcomes of immunopherogrammes have been discussed."}
{"id": "PMID:875", "title": "[Isolation of the individual structural elements of bacteria of the genus Bordetella and a study of their properties. I. The formation of mureinoplasts and true protoplasts from B. pertussis].", "content": "B. pertussis suspension was tested by De Voe et al. method (1970) and its modification with the solutions of a definite ionic composition and a lysozyme. The best results were obtained by the following modification elaborated by the authors. The microbes were grown on the casein-carbon agar for 36 hours and were washed with chilled 0.5 M NaCl. The suspension was washed 4 times with the same solution and then the precipitate was suspended in saccharose solution (0.5 M). In 2 hours the saccharose was replaced by a solution of salts with lysozyme. After a 2-hour incubation at 35 degrees C the substance was centrifugated for 20 minutes and the precipitate suspended in the tris-buffer at pH 7.8. The following changes were observed: after the washing and incubation with saccharose there was seen a strong stretching and separation of the cell wall (CW) from the cytoplasmic membrane (CPM); cells without the CW were rarely revealed; 2) after the lysozyme treatment there were many cells of spherical shape (phasic-contrast microscopy) without any CW, limited by the CPM only. Morphologically they were no different from the true protoplasts of the Gram-positive bacteria. The chemical analysis also confirmed a possibility of obtaining the true protoplasts of the Gram-negative bacteria.", "contents": "[Isolation of the individual structural elements of bacteria of the genus Bordetella and a study of their properties. I. The formation of mureinoplasts and true protoplasts from B. pertussis]. B. pertussis suspension was tested by De Voe et al. method (1970) and its modification with the solutions of a definite ionic composition and a lysozyme. The best results were obtained by the following modification elaborated by the authors. The microbes were grown on the casein-carbon agar for 36 hours and were washed with chilled 0.5 M NaCl. The suspension was washed 4 times with the same solution and then the precipitate was suspended in saccharose solution (0.5 M). In 2 hours the saccharose was replaced by a solution of salts with lysozyme. After a 2-hour incubation at 35 degrees C the substance was centrifugated for 20 minutes and the precipitate suspended in the tris-buffer at pH 7.8. The following changes were observed: after the washing and incubation with saccharose there was seen a strong stretching and separation of the cell wall (CW) from the cytoplasmic membrane (CPM); cells without the CW were rarely revealed; 2) after the lysozyme treatment there were many cells of spherical shape (phasic-contrast microscopy) without any CW, limited by the CPM only. Morphologically they were no different from the true protoplasts of the Gram-positive bacteria. The chemical analysis also confirmed a possibility of obtaining the true protoplasts of the Gram-negative bacteria."}
{"id": "PMID:877", "title": "[Sympathico-adrenal system activity in a primary immune response].", "content": "Experiments were carried out on linear mice immunized with sheep erythrocytes; it was found that the primary immune respose developed against the background of significant changes in the state of the sympathico-adrenal system, whose activity was determined by the dynamics of catecholamines in the blood and in the tissues of a number of organs, including the thymus, the spleen and the lymph nodes. By comparing the value of specific and neurohumoral indices it was revealed that the neurohumoral shifts preceded the maximal development of the immune response. On the example of studying the catecholamine dynamics the opinion on a close association between the state of the regulatory mechanisms and the effector formations responsible for the formation of specific immunological reactions was confirmed. It is suggested that a full-value immunological response developed on condition of activation of the sympathico-adrenal system.", "contents": "[Sympathico-adrenal system activity in a primary immune response]. Experiments were carried out on linear mice immunized with sheep erythrocytes; it was found that the primary immune respose developed against the background of significant changes in the state of the sympathico-adrenal system, whose activity was determined by the dynamics of catecholamines in the blood and in the tissues of a number of organs, including the thymus, the spleen and the lymph nodes. By comparing the value of specific and neurohumoral indices it was revealed that the neurohumoral shifts preceded the maximal development of the immune response. On the example of studying the catecholamine dynamics the opinion on a close association between the state of the regulatory mechanisms and the effector formations responsible for the formation of specific immunological reactions was confirmed. It is suggested that a full-value immunological response developed on condition of activation of the sympathico-adrenal system."}
{"id": "PMID:878", "title": "[Covalent binding of peroxidase to CH- and AH-Sepharose 4 B].", "content": "The properties of peroxidase insolubilized by covalent binding to CH- and AH-Sepharose 4 B in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) are described. CH-Sepharose 4 B bound peroxidase yields an enzyme preparation with a residual specific activity of 60.6%. When bound to AH-Sepharose 4 B, the residual specific activity is to 78%. The reasons of these differences in the catalytic activity of the two insolubilized enzyme preparations are discussed. By covalent binding on CH- and AH-Sepharose 4 B, peroxidase exibits no changes in its pH optimum; it virtually keeps the same activity after being used ten times. Insolubilized peroxidase preparations, dried and reimbibed after being stored for 6 weeks at room temperature still display 50% of the initial specific activity of the insolubilized enzyme. Stored in acetate buffer, the enzyme preparations maintain their activity during all this interval.", "contents": "[Covalent binding of peroxidase to CH- and AH-Sepharose 4 B]. The properties of peroxidase insolubilized by covalent binding to CH- and AH-Sepharose 4 B in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) are described. CH-Sepharose 4 B bound peroxidase yields an enzyme preparation with a residual specific activity of 60.6%. When bound to AH-Sepharose 4 B, the residual specific activity is to 78%. The reasons of these differences in the catalytic activity of the two insolubilized enzyme preparations are discussed. By covalent binding on CH- and AH-Sepharose 4 B, peroxidase exibits no changes in its pH optimum; it virtually keeps the same activity after being used ten times. Insolubilized peroxidase preparations, dried and reimbibed after being stored for 6 weeks at room temperature still display 50% of the initial specific activity of the insolubilized enzyme. Stored in acetate buffer, the enzyme preparations maintain their activity during all this interval."}
{"id": "PMID:879", "title": "Aerobacter aerogenes PRL-R3 urease. Purification and properties.", "content": "A method for the preparation of a 150-fold purified and homogenous A. aerogenes urease is reported. The enzyme exhibited two pH optima at pH 7.0 and 7.5 in triethanolamine and phosphate buffer, respectively. The affinity of the enzyme toward its substrate increased with the increase of pH. No effect of the pH was observed on the measured temperature coefficient (Q10). There was no discontinuity in the Arrhenius plots at pH 5.4 and 7.5 but an upward discontinuity at pH 6.15 and 8.7 with transition temperature at 30 degrees C. Also, the calculated activation energies are greatly affected by the pH of the enzyme reaction mixture.", "contents": "Aerobacter aerogenes PRL-R3 urease. Purification and properties. A method for the preparation of a 150-fold purified and homogenous A. aerogenes urease is reported. The enzyme exhibited two pH optima at pH 7.0 and 7.5 in triethanolamine and phosphate buffer, respectively. The affinity of the enzyme toward its substrate increased with the increase of pH. No effect of the pH was observed on the measured temperature coefficient (Q10). There was no discontinuity in the Arrhenius plots at pH 5.4 and 7.5 but an upward discontinuity at pH 6.15 and 8.7 with transition temperature at 30 degrees C. Also, the calculated activation energies are greatly affected by the pH of the enzyme reaction mixture."}
{"id": "PMID:880", "title": "Further characterization of the association of glyceraldehyde-3-phosphate dehydrogenase with reticulocyte membranes.", "content": "1. The behaviour and properties of membrane-bound GAPDH of rabbit reticulocytes were investigated. 2. The bound GAPDH is more resistant to inactivation by KCl than the soluble enzyme (allotopy). 3. The bound enzyme is released by electrolytes. This effect does not only depend on the ionic strength but additionally on the kind of ions, pH-value and protein concentration. 4. A comparison of the releasing effect of NAD analogues shows the necessity of the 5'-AMP moiety in the structure of the effector. 5. The represented results demonstrate the specifity of the GAPDH-membrane binding in rabbit reticulocytes.", "contents": "Further characterization of the association of glyceraldehyde-3-phosphate dehydrogenase with reticulocyte membranes. 1. The behaviour and properties of membrane-bound GAPDH of rabbit reticulocytes were investigated. 2. The bound GAPDH is more resistant to inactivation by KCl than the soluble enzyme (allotopy). 3. The bound enzyme is released by electrolytes. This effect does not only depend on the ionic strength but additionally on the kind of ions, pH-value and protein concentration. 4. A comparison of the releasing effect of NAD analogues shows the necessity of the 5'-AMP moiety in the structure of the effector. 5. The represented results demonstrate the specifity of the GAPDH-membrane binding in rabbit reticulocytes."}
{"id": "PMID:881", "title": "[Effect of the vagus nerve on isolated rabbit atria in ganglionic blockade due to hexamethonium].", "content": "By quantitative stimulation of the vagus nerves of isolated rabbit atria frequency-response relations were obtained for both the electrotropic effect (reduction of the area of the monophasic action potential) and the inotropic response. An addition of hexamethonium in a final concentration of 10(-5) g/ml resulted in a diminution of vagal effectivity in the range of lower and medium frequencies of stimulation, and was connected with a shift of the frequency-response characteristic to the right. At higher frequencies vagal effectivity was increased. In contrast to the inhibitory effect of hexamethonium the facilitating action is irreversible. By raising the concentration up to 4-10(-5) g/ml the vagal effects were reduced to a large extent, and the frequency dependence of the response was abolished at medium frequencies. In the range of 20 sec(-1) to 100 sec(-1) this dependence was re-established and may be considered as a part of a normal frequency-response relation extremely shifted to the right. The time courses of both types of effect are characterized by a steep rise and a decay of the response during the stimulation period. A mathematical handling of the frequency-response characteristics provides quantitative evidence for the extent of the hexamethonium blockade of vagal ganglion cells in the atria; furthermore it leads to the conception of these cells to act as a distributing system for a homogeneous innervation by a widespread divergency of postganglionic fibres.", "contents": "[Effect of the vagus nerve on isolated rabbit atria in ganglionic blockade due to hexamethonium]. By quantitative stimulation of the vagus nerves of isolated rabbit atria frequency-response relations were obtained for both the electrotropic effect (reduction of the area of the monophasic action potential) and the inotropic response. An addition of hexamethonium in a final concentration of 10(-5) g/ml resulted in a diminution of vagal effectivity in the range of lower and medium frequencies of stimulation, and was connected with a shift of the frequency-response characteristic to the right. At higher frequencies vagal effectivity was increased. In contrast to the inhibitory effect of hexamethonium the facilitating action is irreversible. By raising the concentration up to 4-10(-5) g/ml the vagal effects were reduced to a large extent, and the frequency dependence of the response was abolished at medium frequencies. In the range of 20 sec(-1) to 100 sec(-1) this dependence was re-established and may be considered as a part of a normal frequency-response relation extremely shifted to the right. The time courses of both types of effect are characterized by a steep rise and a decay of the response during the stimulation period. A mathematical handling of the frequency-response characteristics provides quantitative evidence for the extent of the hexamethonium blockade of vagal ganglion cells in the atria; furthermore it leads to the conception of these cells to act as a distributing system for a homogeneous innervation by a widespread divergency of postganglionic fibres."}
{"id": "PMID:882", "title": "Chemical relaxation studies on the system liver alcohol dehydrogenase, NADH and imidazole.", "content": "Several years ago, Theorell and Czerlinski conducted experiments on the system of horse liver alcohol dehydrogenase, reduced nicotinamide adenine dinucleotide and imidazole, using the first version of the temperature jump apparatus with detection of changes in fluorescence. These early experiments were repeated with improved instrumentation and confirmed the early experiments in general terms. However, the improved detection system allowed to measure a slight concentration dependence of the relaxation time of around 3 ms. Furthermore, the chemical relaxation time was smaller than the one determined earlier (by factor 2). The data were evaluated much more rigorously than before, allowing an appropriate interpretation of the results. The observed relaxation time is largely due to rate constants in an interconversion of ternary complexes, which are faster than three (of the four) dissociation rate constants, determined previously by Theorell and McKinley-McKee.1,2 This fact contributed to earlier difficulties of finding any concentration dependence. However, the binding of imidazole to the binary enzyme-coenzyme complex can be made to couple kinetically into the interconversion rate of the two ternary complexes. The observed signal derives largely from the ternary complex(es). A substantial fluorescence signal change is associated with the observed relaxation process, suggesting a relocation of the imidazole in reference to the nicotinamide moiety of the bound coenzyme. Nine models are considered with two types of coupling of pre-equilibria (none-all). Quantitative evaluations favor the model with two ternary complexes connected by an interconversion outside the four-step (bimolecular) cycle. The ternary complex outside the cycle has much higher fluorescence yield than the one inside. The interconversion equilibrium is near unity for imidazole. If it would be shifted very much to the side of the \"dead-end\" complex (as in isobutyramide?!), stimulating action could not take place.", "contents": "Chemical relaxation studies on the system liver alcohol dehydrogenase, NADH and imidazole. Several years ago, Theorell and Czerlinski conducted experiments on the system of horse liver alcohol dehydrogenase, reduced nicotinamide adenine dinucleotide and imidazole, using the first version of the temperature jump apparatus with detection of changes in fluorescence. These early experiments were repeated with improved instrumentation and confirmed the early experiments in general terms. However, the improved detection system allowed to measure a slight concentration dependence of the relaxation time of around 3 ms. Furthermore, the chemical relaxation time was smaller than the one determined earlier (by factor 2). The data were evaluated much more rigorously than before, allowing an appropriate interpretation of the results. The observed relaxation time is largely due to rate constants in an interconversion of ternary complexes, which are faster than three (of the four) dissociation rate constants, determined previously by Theorell and McKinley-McKee.1,2 This fact contributed to earlier difficulties of finding any concentration dependence. However, the binding of imidazole to the binary enzyme-coenzyme complex can be made to couple kinetically into the interconversion rate of the two ternary complexes. The observed signal derives largely from the ternary complex(es). A substantial fluorescence signal change is associated with the observed relaxation process, suggesting a relocation of the imidazole in reference to the nicotinamide moiety of the bound coenzyme. Nine models are considered with two types of coupling of pre-equilibria (none-all). Quantitative evaluations favor the model with two ternary complexes connected by an interconversion outside the four-step (bimolecular) cycle. The ternary complex outside the cycle has much higher fluorescence yield than the one inside. The interconversion equilibrium is near unity for imidazole. If it would be shifted very much to the side of the \"dead-end\" complex (as in isobutyramide?!), stimulating action could not take place."}
{"id": "PMID:884", "title": "Comparative study of virological infections in asthmatic and nonasthmatic children.", "content": "The author shows complex analyses: clinical, laboratory, X-rays, bronchoscopical, bronchographical and measuring lung function tests as well as the serological examinations in blood serum of both groups of asthmatic and nonasthmatic children with virological infection. The calculation of statistically significant differences between the various diagnostical results of both groups has confirmed that in asthmatic children virological infection of the respiratory tract, pathological findings in X-ray and lung function tests, bronchiectasis and secondary bacteriological invasion occurs statistically significantly more often than in nonasthmatic children.", "contents": "Comparative study of virological infections in asthmatic and nonasthmatic children. The author shows complex analyses: clinical, laboratory, X-rays, bronchoscopical, bronchographical and measuring lung function tests as well as the serological examinations in blood serum of both groups of asthmatic and nonasthmatic children with virological infection. The calculation of statistically significant differences between the various diagnostical results of both groups has confirmed that in asthmatic children virological infection of the respiratory tract, pathological findings in X-ray and lung function tests, bronchiectasis and secondary bacteriological invasion occurs statistically significantly more often than in nonasthmatic children."}
{"id": "PMID:886", "title": "Multiple forms of staphylococcal alpha-toxin.", "content": "A group of proteins was readily extracted at neutrality from trichloroacetic acid precipitates of staphylococcal culture filtrate supernatants, while alpha-toxin was dissolved and activated by treating the precipitate with 8 M urea, with acidic buffers or by heating to 90-100 degrees C at neutrality. Heat activation of the precipitate produced a relatively pure alpha-toxin with a molecular weight of 39,000. alpha-Toxin was eluted together with three other proteins on hydroxyl apatite chromatography, and evidence was obtained for an association between the four proteins. On isoelectric focusing a haemolytic fraction was obtained at pH 6.2, probably due to acid activation of the precipitate formed at the cathodic end of the column. The alpha-haemolytic fractions with pI's of 7.4 and 8.6 were shown to consist of alpha-toxin only when analyzed by acrylamide electrophoresis in the presence of sodium dodecyl sulphate. The haemolytic component with a pI of 9.2 contained two additional components of molecular weights of 27,500 and 18,000. Chromatography of this material on Sephadex G-200 showed that alpha-toxin and the two proteins appeared as a high molecular complex.", "contents": "Multiple forms of staphylococcal alpha-toxin. A group of proteins was readily extracted at neutrality from trichloroacetic acid precipitates of staphylococcal culture filtrate supernatants, while alpha-toxin was dissolved and activated by treating the precipitate with 8 M urea, with acidic buffers or by heating to 90-100 degrees C at neutrality. Heat activation of the precipitate produced a relatively pure alpha-toxin with a molecular weight of 39,000. alpha-Toxin was eluted together with three other proteins on hydroxyl apatite chromatography, and evidence was obtained for an association between the four proteins. On isoelectric focusing a haemolytic fraction was obtained at pH 6.2, probably due to acid activation of the precipitate formed at the cathodic end of the column. The alpha-haemolytic fractions with pI's of 7.4 and 8.6 were shown to consist of alpha-toxin only when analyzed by acrylamide electrophoresis in the presence of sodium dodecyl sulphate. The haemolytic component with a pI of 9.2 contained two additional components of molecular weights of 27,500 and 18,000. Chromatography of this material on Sephadex G-200 showed that alpha-toxin and the two proteins appeared as a high molecular complex."}
{"id": "PMID:885", "title": "Acute otitis media. A clinical bacteriological and serological study of children with frequent episodes of acute otitis media.", "content": "A series of episodes of acute otitis media was studied with reference to bacterial findings and specific serological responses in 48 children with histories of frequent episodes before. D. pneumoniae and H. influenzae were the most frequently isolated pathogens. Re-isolations after therapy were often made in episodes with slow healing or therapeutic failure. Most children harboured pathogens in nasopharynx even when they had no signs of respiratory tract infections. Homologous relapses were seen only in few cases and never with pneumococcus type 3 and only once with H. influenzae type b. Specific serological responses were demonstrable generally in children over 2 years of age. D. pneumococcus type 3 and H. influenzae type b generally provoked antibody response. No levels indicating immunoglobulin deficiencies could be found in the children.", "contents": "Acute otitis media. A clinical bacteriological and serological study of children with frequent episodes of acute otitis media. A series of episodes of acute otitis media was studied with reference to bacterial findings and specific serological responses in 48 children with histories of frequent episodes before. D. pneumoniae and H. influenzae were the most frequently isolated pathogens. Re-isolations after therapy were often made in episodes with slow healing or therapeutic failure. Most children harboured pathogens in nasopharynx even when they had no signs of respiratory tract infections. Homologous relapses were seen only in few cases and never with pneumococcus type 3 and only once with H. influenzae type b. Specific serological responses were demonstrable generally in children over 2 years of age. D. pneumococcus type 3 and H. influenzae type b generally provoked antibody response. No levels indicating immunoglobulin deficiencies could be found in the children."}
{"id": "PMID:899", "title": "Endosymbiosis and cellular tolerance in the Hawaiian soft coral Sarcothelia edmondsoni verrill.", "content": "The relationship between the soft coral Sarcothelia edmondsoni Verrill and its symbiotic algae is considered as an early instance of cellular tolerance which can be disturbed by a variety of adverse conditions. The algal cells lie in vesicles deep within the endodermal cells of the host and are not subject to digestion. Their expulsion appears to be a reverse translocation to the distal end of the host cell and escape by a form of reversed phagocytosis resembling secretion. The cellular mechanisms involved are not clear.", "contents": "Endosymbiosis and cellular tolerance in the Hawaiian soft coral Sarcothelia edmondsoni verrill. The relationship between the soft coral Sarcothelia edmondsoni Verrill and its symbiotic algae is considered as an early instance of cellular tolerance which can be disturbed by a variety of adverse conditions. The algal cells lie in vesicles deep within the endodermal cells of the host and are not subject to digestion. Their expulsion appears to be a reverse translocation to the distal end of the host cell and escape by a form of reversed phagocytosis resembling secretion. The cellular mechanisms involved are not clear."}
{"id": "PMID:906", "title": "Epidemiologic investigations of the 1969 epidemic of Venezuelan encephalitis in Ecuador.", "content": "An epizoodemic of Venezuelan equine encephalitis (VEE), subtype I variant B, occurred in Ecuador during the rainy and hot season of 1969. In this paper, a general description of the epidemic is given and virus isolations from humans are reported. A serologic survey was performed in order to determine the extension of the epidemic along the coastal zone of the country. It is not clear whether the higher antibody rate in older people was because they were at greater risk of infection or was the result of an accumulated immunity with time. The latter could be an indication of endemic virus activity, not yet proven for the VEE IB virus variant. Mosquito surveillance and attempted control by aerial spraying were carried out.", "contents": "Epidemiologic investigations of the 1969 epidemic of Venezuelan encephalitis in Ecuador. An epizoodemic of Venezuelan equine encephalitis (VEE), subtype I variant B, occurred in Ecuador during the rainy and hot season of 1969. In this paper, a general description of the epidemic is given and virus isolations from humans are reported. A serologic survey was performed in order to determine the extension of the epidemic along the coastal zone of the country. It is not clear whether the higher antibody rate in older people was because they were at greater risk of infection or was the result of an accumulated immunity with time. The latter could be an indication of endemic virus activity, not yet proven for the VEE IB virus variant. Mosquito surveillance and attempted control by aerial spraying were carried out."}
{"id": "PMID:907", "title": "Congenital malformations of the central nervous system produced by narcotic analgesics in the hamster.", "content": "Maternal dose--fetal teratogenic response data were obtained for a variety of narcotic and related compounds by single subcutaneous injections of the drugs into pregnant hamsters during the critical periods of central nervous system organogenesis. The number of abnormal fetuses from females injected with diacetylmorphine (heroin), thebaine, phenazocine, pentazocine, propoxyphene, and methadone increased as the maternal dose of the compounds was increased. By contrast, morphine, hydromorphone, and meperidine produced an increase in the number (per cent) of fetal anomalies only up to a certain maternal dose level. Further increases in maternal dose levels did not produce additional fetal anomalies. Comparative studies of single and multiple maternal doses indicated that diacetylmorphine (heroin) and methadone produced a four- to sixfold increase in fetal anomalies with repetitive doses whereas the percentage of malformed fetuses remained the same with hydromorphone (Dilaudid). The narcotic antagonists nalorphine, naloxone, levallophan, and cyclazocine blocked the teratogenic effects of both single and multiple doses of the narcotics.", "contents": "Congenital malformations of the central nervous system produced by narcotic analgesics in the hamster. Maternal dose--fetal teratogenic response data were obtained for a variety of narcotic and related compounds by single subcutaneous injections of the drugs into pregnant hamsters during the critical periods of central nervous system organogenesis. The number of abnormal fetuses from females injected with diacetylmorphine (heroin), thebaine, phenazocine, pentazocine, propoxyphene, and methadone increased as the maternal dose of the compounds was increased. By contrast, morphine, hydromorphone, and meperidine produced an increase in the number (per cent) of fetal anomalies only up to a certain maternal dose level. Further increases in maternal dose levels did not produce additional fetal anomalies. Comparative studies of single and multiple maternal doses indicated that diacetylmorphine (heroin) and methadone produced a four- to sixfold increase in fetal anomalies with repetitive doses whereas the percentage of malformed fetuses remained the same with hydromorphone (Dilaudid). The narcotic antagonists nalorphine, naloxone, levallophan, and cyclazocine blocked the teratogenic effects of both single and multiple doses of the narcotics."}
{"id": "PMID:908", "title": "Evaluation of a non-professional visual screening method.", "content": "A screening method designed for administration by lay personnel is evaluated and compared to Modified Clinical Technique screening results for a screening of 1600 elementary school children.", "contents": "Evaluation of a non-professional visual screening method. A screening method designed for administration by lay personnel is evaluated and compared to Modified Clinical Technique screening results for a screening of 1600 elementary school children."}
{"id": "PMID:909", "title": "Ionic requirements of proximal tubular sodium transport. II. Hydrogen ion.", "content": "Simultaneous perfusion to proximal convoluted tubules and peritubular capillaries was used to study the effects of different perfusion fluids on sodium reabsorption and hydrogen secretion, which was calculated as bicarbonate reabsorption and titratable acid. Results show that sodium reabsorption was not tightly coupled to hydrogen secretion. Bicarbonate stimulates both sodium reabsorption and hydrogen secretion, but Tris stimulates only sodium reabsorption. Imposing an adverse chloride gradient across the proximal tubule (C1- peritubular greater than C1- luminal) decreased sodium reabsorption but did not diminish hydrogen secretion. Diamox inhibited both net sodium and hydrogen transport. It is concluded that there is not firm linkage between sodium reabsorption and hydrogen secretion and that bicarbonate probably stimulates sodium transport by a number of mechanisms, including an effect on the sodium transport unrelated to its ability to increase hydrogen ion secretion.", "contents": "Ionic requirements of proximal tubular sodium transport. II. Hydrogen ion. Simultaneous perfusion to proximal convoluted tubules and peritubular capillaries was used to study the effects of different perfusion fluids on sodium reabsorption and hydrogen secretion, which was calculated as bicarbonate reabsorption and titratable acid. Results show that sodium reabsorption was not tightly coupled to hydrogen secretion. Bicarbonate stimulates both sodium reabsorption and hydrogen secretion, but Tris stimulates only sodium reabsorption. Imposing an adverse chloride gradient across the proximal tubule (C1- peritubular greater than C1- luminal) decreased sodium reabsorption but did not diminish hydrogen secretion. Diamox inhibited both net sodium and hydrogen transport. It is concluded that there is not firm linkage between sodium reabsorption and hydrogen secretion and that bicarbonate probably stimulates sodium transport by a number of mechanisms, including an effect on the sodium transport unrelated to its ability to increase hydrogen ion secretion."}
{"id": "PMID:910", "title": "ECS, intracellular pH, and electrolytes of cardiac and skeletal muscle.", "content": "The extracellular space (ECS) of muscle from each ventricle of the heart (RV and LV), the atria, diaphragm, and quadriceps was estimated in the anesthetized rabbit from the distribution volumes of [14C]insulin, [14C]sucrose, [51Cr]EDTA, and C1--. Whole-tissue electrolytes were measured and intracellular electrolytes calculated. The ECS of the tissues varied, increasing in the order quadriceps less than LV less than RV less than atria. The volume of distribution of [14C]inulin was always less than that of either [14C]sucrose or [51Cr]EDTA which agreed closely, whereas that of C1-- was always greater. There was no difference in intracellular K+ in muscle from each of the cardiac chambers, whereas intracellular Na+ and C1-- varied, increasing in the order quadriceps less than LV less than RV less than atria. Intracellular pH, measured with [14C]DMO did not differ in any of the tissues studied. It is concluded that, in vivo, the estimated ECS incardiac muscle is lower than that reported in vitro, that [51Cr]EDTA is a satisfactory ECS marker, and that differences in intracellular Na+ and C1-- but not K+ or pH exist between muscle from the cardiac chambers.", "contents": "ECS, intracellular pH, and electrolytes of cardiac and skeletal muscle. The extracellular space (ECS) of muscle from each ventricle of the heart (RV and LV), the atria, diaphragm, and quadriceps was estimated in the anesthetized rabbit from the distribution volumes of [14C]insulin, [14C]sucrose, [51Cr]EDTA, and C1--. Whole-tissue electrolytes were measured and intracellular electrolytes calculated. The ECS of the tissues varied, increasing in the order quadriceps less than LV less than RV less than atria. The volume of distribution of [14C]inulin was always less than that of either [14C]sucrose or [51Cr]EDTA which agreed closely, whereas that of C1-- was always greater. There was no difference in intracellular K+ in muscle from each of the cardiac chambers, whereas intracellular Na+ and C1-- varied, increasing in the order quadriceps less than LV less than RV less than atria. Intracellular pH, measured with [14C]DMO did not differ in any of the tissues studied. It is concluded that, in vivo, the estimated ECS incardiac muscle is lower than that reported in vitro, that [51Cr]EDTA is a satisfactory ECS marker, and that differences in intracellular Na+ and C1-- but not K+ or pH exist between muscle from the cardiac chambers."}
{"id": "PMID:911", "title": "Intracellular pH and K+ of cardiac and skeletal muscle in acidosis and alkalosis.", "content": "The effects of a metabolic and respiratory acidosis and alkalosis on intracellular pH (pHi) and K+ have been compared in cardiac and skeletal muscle from the anesthetized rabbit. The extracellular space and pHi were calculated from the distribution volumes of [51Cr] EDTA and [14C]DMO, respectively. When pHe was varied by altering PCO2, the slope of the line relating pHi to the extracellular pH (pHe) was greater (P less than 0.05--0.001) than that obtained during metabolic changes of pHe in right and left ventricles, atria, diaphragm, and quadriceps. During metabolic acidosis and alkalosis, the slope of pHi/pHe line did not vary between tissues. During respiratory acidosis, there was no difference in slope between cardiac tissues, but it was less in left ventricle than quadriceps (P less than 0.001). In left ventricle intracellular K+ increased in a metabolic (P less than 0.05) or respiratory acidosis (P less than 0.02), whereas in diaphragm it decreased (P less than 0.02). Intracellular K+ correlated with pHe and pHE-PHi. Changes in pHi but not intracellular K+ could explain known differences in myocardial function in respiratory and metabolic acidosis.", "contents": "Intracellular pH and K+ of cardiac and skeletal muscle in acidosis and alkalosis. The effects of a metabolic and respiratory acidosis and alkalosis on intracellular pH (pHi) and K+ have been compared in cardiac and skeletal muscle from the anesthetized rabbit. The extracellular space and pHi were calculated from the distribution volumes of [51Cr] EDTA and [14C]DMO, respectively. When pHe was varied by altering PCO2, the slope of the line relating pHi to the extracellular pH (pHe) was greater (P less than 0.05--0.001) than that obtained during metabolic changes of pHe in right and left ventricles, atria, diaphragm, and quadriceps. During metabolic acidosis and alkalosis, the slope of pHi/pHe line did not vary between tissues. During respiratory acidosis, there was no difference in slope between cardiac tissues, but it was less in left ventricle than quadriceps (P less than 0.001). In left ventricle intracellular K+ increased in a metabolic (P less than 0.05) or respiratory acidosis (P less than 0.02), whereas in diaphragm it decreased (P less than 0.02). Intracellular K+ correlated with pHe and pHE-PHi. Changes in pHi but not intracellular K+ could explain known differences in myocardial function in respiratory and metabolic acidosis."}
{"id": "PMID:912", "title": "Effects of autonomic neurohumors on transmembrane potentials of atrial plateau fibers.", "content": "Isolated canine atrial plateau fibers were treated with acetylcholine or norepinephrine to note the effects on the transmembrane potential. Acetylcholine, 1.0 or 2.0 mug/ml, consistently reduced the slope of inherent phase 4 depolarization. Increases in maximum diastolic potential and rising velocity occurred along with a decrease in overshoot. The plateau phase disappeared. Pretreatment with atropine, 1.0 mug/ml, prevented these responses, and alone this drug had no discernible effect. Norepinephrine consistently increased the slope of phase 4 depolarization. Frequently plateau fibers generated action potentials by the normal pacemaker mechanism. \"Arrhythmias\" characterized by spontaneous excitations were induced in 92% of the norepinephrine experiments. Norepinephrine also enhanced the plateau phase of the action potential and decreased the rising velocity and overshoot. Racemic propranolol, 1.0 mug/ml, blocked all the above effects including arrhythmias. Dextropropranolol, 1.0 mug/ml, did not block effects produced by norepinephrine. Acetylcholine, applied to fibers under treatment with norepinephrine, reduced the slope of norepinephrine-induced phase 4 depolarization and terminated induced arrhythmias.", "contents": "Effects of autonomic neurohumors on transmembrane potentials of atrial plateau fibers. Isolated canine atrial plateau fibers were treated with acetylcholine or norepinephrine to note the effects on the transmembrane potential. Acetylcholine, 1.0 or 2.0 mug/ml, consistently reduced the slope of inherent phase 4 depolarization. Increases in maximum diastolic potential and rising velocity occurred along with a decrease in overshoot. The plateau phase disappeared. Pretreatment with atropine, 1.0 mug/ml, prevented these responses, and alone this drug had no discernible effect. Norepinephrine consistently increased the slope of phase 4 depolarization. Frequently plateau fibers generated action potentials by the normal pacemaker mechanism. \"Arrhythmias\" characterized by spontaneous excitations were induced in 92% of the norepinephrine experiments. Norepinephrine also enhanced the plateau phase of the action potential and decreased the rising velocity and overshoot. Racemic propranolol, 1.0 mug/ml, blocked all the above effects including arrhythmias. Dextropropranolol, 1.0 mug/ml, did not block effects produced by norepinephrine. Acetylcholine, applied to fibers under treatment with norepinephrine, reduced the slope of norepinephrine-induced phase 4 depolarization and terminated induced arrhythmias."}
{"id": "PMID:913", "title": "Interstitial fluid pressure and alkaline gastric secretion.", "content": "The interstitial fluid pressure of the submucosa of the gastric fundus was monitored by means of Guyton's capsules in dogs anesthetized with pentobarbital. The intracapsular pressure (ICP) was measured during secretion produced by: a) hypertonic solutions placed inside the stomach; b) arterial hypertension (200 mmHg) applied during intra-arterial infusion of histamine, and c) intra-arterial infusion of acetylcholine. The first procedure did not modify the ICP. On the other hand, whenever interstitial fluid appeared in the gastric lumen during hypertension plus histamine, the mean ICP increased, mostly due to augmented capillary filtration. The hydraulic coefficient measured in these experiments was at least 4 orders of magnitude larger than the respective osmotic coefficient. The action of acetylcholine was complex: large doses enlarged the net capillary filtration, but small doses increased the mean ICP by muscle stimulation only. Contraction of the muscularis mucosae might be the most important mechanism underlying bulk flow of interstitial fluid in physiological conditions. It is concluded that hydraulic gradients across the epithelium might account for the \"secretion\" of \"alkaline\" juice.", "contents": "Interstitial fluid pressure and alkaline gastric secretion. The interstitial fluid pressure of the submucosa of the gastric fundus was monitored by means of Guyton's capsules in dogs anesthetized with pentobarbital. The intracapsular pressure (ICP) was measured during secretion produced by: a) hypertonic solutions placed inside the stomach; b) arterial hypertension (200 mmHg) applied during intra-arterial infusion of histamine, and c) intra-arterial infusion of acetylcholine. The first procedure did not modify the ICP. On the other hand, whenever interstitial fluid appeared in the gastric lumen during hypertension plus histamine, the mean ICP increased, mostly due to augmented capillary filtration. The hydraulic coefficient measured in these experiments was at least 4 orders of magnitude larger than the respective osmotic coefficient. The action of acetylcholine was complex: large doses enlarged the net capillary filtration, but small doses increased the mean ICP by muscle stimulation only. Contraction of the muscularis mucosae might be the most important mechanism underlying bulk flow of interstitial fluid in physiological conditions. It is concluded that hydraulic gradients across the epithelium might account for the \"secretion\" of \"alkaline\" juice."}
{"id": "PMID:914", "title": "Overview: maintenance therapy in psychiatry: I. Schizophrenia.", "content": "Hospital psychiatry has evolved from long-term \"treatment\" programs that were primarily custodial to the successful pharmacological treatment of acute psychotic episodes. Unfortunately, many patients still return to the hospital with relapses. This so-called revolving door syndrome draws attention to the critical importance of preventing as well as treating acute episodes. In the first part of this overview, the author reviews the clinical literature on prophylactic treatment of schizophrenia with maintenance antipsychotic drugs. The second part will review the literature on prophylactic treatment of affective disorders with lithium and tricyclics. In the opinion of the author these drugs provide the potential for truly preventive psychiatry.", "contents": "Overview: maintenance therapy in psychiatry: I. Schizophrenia. Hospital psychiatry has evolved from long-term \"treatment\" programs that were primarily custodial to the successful pharmacological treatment of acute psychotic episodes. Unfortunately, many patients still return to the hospital with relapses. This so-called revolving door syndrome draws attention to the critical importance of preventing as well as treating acute episodes. In the first part of this overview, the author reviews the clinical literature on prophylactic treatment of schizophrenia with maintenance antipsychotic drugs. The second part will review the literature on prophylactic treatment of affective disorders with lithium and tricyclics. In the opinion of the author these drugs provide the potential for truly preventive psychiatry."}
{"id": "PMID:915", "title": "Inpatient and outpatient patterns of psychotropic drug prescribing by nonpsychiatrist physicians.", "content": "The authors found that among 228 general hospital patients, minor tranquilizers were prescribed most often and with the least justification and that major tranquilizers were prescribed sparingly and by and large judiciously. Antidepressants were given less often than would be justified by the incidence of depressive illness among these patients. Nonrecognition of depression in patients with somatic complaints and autonomic signs of depression contributed to this lack of treatment.", "contents": "Inpatient and outpatient patterns of psychotropic drug prescribing by nonpsychiatrist physicians. The authors found that among 228 general hospital patients, minor tranquilizers were prescribed most often and with the least justification and that major tranquilizers were prescribed sparingly and by and large judiciously. Antidepressants were given less often than would be justified by the incidence of depressive illness among these patients. Nonrecognition of depression in patients with somatic complaints and autonomic signs of depression contributed to this lack of treatment."}
{"id": "PMID:920", "title": "[Metabolic acidosis as a side-effect of methoxyflurane anesthesia (author's transl)].", "content": "In 14 patients undergoing surgery with methoxyflurane anaesthesia the development of metabolic acidosis was observed. As mechanisms causing such acidosis regional ischaemia and inhibition of lactic acid metabolism in the liver by breakdown products of methoxyflurane are discussed.", "contents": "[Metabolic acidosis as a side-effect of methoxyflurane anesthesia (author's transl)]. In 14 patients undergoing surgery with methoxyflurane anaesthesia the development of metabolic acidosis was observed. As mechanisms causing such acidosis regional ischaemia and inhibition of lactic acid metabolism in the liver by breakdown products of methoxyflurane are discussed."}
{"id": "PMID:930", "title": "Protective effect of hypothermia in cerebral oxygen deficiency caused by arterial hypoxia.", "content": "To study the cerebral protective effects of hypothermia in arterial hypoxia, anesthetized (70% N2O), mechanically ventilated rats were cooled to a body temperature of 27 C. Hypoxia was induced by decreasing the oxygen content in the inspired gas mixture either to 6-7 per cent or to 2.5-3 per cent. This reduced mean PaO2 to about 25 and 11-12 torr, respectively. At PaO2 torr, there was no change in cerebral blood flow (CBF), cerebrla oxygen consumption (CMRO2), or labile tissue metabolites. The absence of signs of cerebral hypoxia could be attributed to an effect of temperature and pH on the hemoglobin-oxygen dissociation curve. Thus, at 27 C with a PaO2 of 25 torr the total oxygen content (TO2) of arterial blood remained greater than 15 ml (100 ml)-1, about three times the value obtained at this PO2 in normothermic rats. At PaO2 11-12 torr, arterial TO2 was reduced to about 5 ml (100 ml) (-1). The hypoxia induced no change in CMRO2, a threefold increase in CBF, a moderate lactacidosis in the tissue, and a small decrease in phosphocreatine content, but no change in ATP, ADP, or AMP. These changes are less marked than those occurring at the same arterial TO2 in normothermic rats. It is concluded that hypothermia exerts a pronounced protective effect on the brain in hypoxic hypoxia, and that two mechanisms are involved. First, since hypothermia shifts the oxyhemoglobin-dissociation curve towards the left, and prevents or minimizes a rightward shift due to acidosis, it maintains a high TO2 in arterial blood at a given PaO2. Second, by reducing CMRO2, and thereby presumably also cellular energy requirements, hypothermia exerts a protective effect at the cellular level.", "contents": "Protective effect of hypothermia in cerebral oxygen deficiency caused by arterial hypoxia. To study the cerebral protective effects of hypothermia in arterial hypoxia, anesthetized (70% N2O), mechanically ventilated rats were cooled to a body temperature of 27 C. Hypoxia was induced by decreasing the oxygen content in the inspired gas mixture either to 6-7 per cent or to 2.5-3 per cent. This reduced mean PaO2 to about 25 and 11-12 torr, respectively. At PaO2 torr, there was no change in cerebral blood flow (CBF), cerebrla oxygen consumption (CMRO2), or labile tissue metabolites. The absence of signs of cerebral hypoxia could be attributed to an effect of temperature and pH on the hemoglobin-oxygen dissociation curve. Thus, at 27 C with a PaO2 of 25 torr the total oxygen content (TO2) of arterial blood remained greater than 15 ml (100 ml)-1, about three times the value obtained at this PO2 in normothermic rats. At PaO2 11-12 torr, arterial TO2 was reduced to about 5 ml (100 ml) (-1). The hypoxia induced no change in CMRO2, a threefold increase in CBF, a moderate lactacidosis in the tissue, and a small decrease in phosphocreatine content, but no change in ATP, ADP, or AMP. These changes are less marked than those occurring at the same arterial TO2 in normothermic rats. It is concluded that hypothermia exerts a pronounced protective effect on the brain in hypoxic hypoxia, and that two mechanisms are involved. First, since hypothermia shifts the oxyhemoglobin-dissociation curve towards the left, and prevents or minimizes a rightward shift due to acidosis, it maintains a high TO2 in arterial blood at a given PaO2. Second, by reducing CMRO2, and thereby presumably also cellular energy requirements, hypothermia exerts a protective effect at the cellular level."}
{"id": "PMID:933", "title": "Characterization of a caprine herpesvirus.", "content": "A virus, which was isolated from kids (Capra hircus) affected with a relatively severe generalized infection, was found to contain DNA and to have a buoyant density of 1.2820 g/cm3. The virus was sensitive to the action of lipid solvents and trypsin and was rapidly inactivated at pH 3.0 and at temperatures of 50 and 56 C. The virion, an icosahedron consisting of a nucleoid surrounded by a double membrane, measured approximately 135 nm in diameter. On the basis of its chemical and physical properties, the virus is considered a herpesvirus.", "contents": "Characterization of a caprine herpesvirus. A virus, which was isolated from kids (Capra hircus) affected with a relatively severe generalized infection, was found to contain DNA and to have a buoyant density of 1.2820 g/cm3. The virus was sensitive to the action of lipid solvents and trypsin and was rapidly inactivated at pH 3.0 and at temperatures of 50 and 56 C. The virion, an icosahedron consisting of a nucleoid surrounded by a double membrane, measured approximately 135 nm in diameter. On the basis of its chemical and physical properties, the virus is considered a herpesvirus."}
{"id": "PMID:934", "title": "Transfer of drugs across the ruminal wall in goats.", "content": "The rates at which pentobarbital, salicylate, antipyrine, and quinine were transferred from the rumen of intact, conscious goats were measured. The rates at which the same drugs diffused from the blood plasma (under conditions of constant drug concentration) into the ruminal solution were also evaluated. These compounds were absorbed by simple diffusion, and the rates of transfer were a function of pH of the intraruminal solution. The diffusion of drugs from plasma into the reticulorumen allowed steady-state distributions to be established in some goats. The theoretical and observed steady-state distributions were compared. There were good correlations for pentobarbital and antipyrine, but not for salicylate and quinine. These findings confirm in vivo the general principles of drug transfer across ruminal epithelium that were derived from previous studies conducted in vitro.", "contents": "Transfer of drugs across the ruminal wall in goats. The rates at which pentobarbital, salicylate, antipyrine, and quinine were transferred from the rumen of intact, conscious goats were measured. The rates at which the same drugs diffused from the blood plasma (under conditions of constant drug concentration) into the ruminal solution were also evaluated. These compounds were absorbed by simple diffusion, and the rates of transfer were a function of pH of the intraruminal solution. The diffusion of drugs from plasma into the reticulorumen allowed steady-state distributions to be established in some goats. The theoretical and observed steady-state distributions were compared. There were good correlations for pentobarbital and antipyrine, but not for salicylate and quinine. These findings confirm in vivo the general principles of drug transfer across ruminal epithelium that were derived from previous studies conducted in vitro."}
{"id": "PMID:935", "title": "Preservation of hypoxic pulmonary pressor response in canine pneumococcal pneumonia.", "content": "To determine the role of hypoxic pulmonary vasoconstriction in pneumococcal pneumonia, hemodynamic measurements were made in 16 dogs before, and within 36 hours after, intrapulmonary administration of type III pneumococcus. Ten dogs with one lobe or more of pneumonia increased their pulmonary vascular resistances and slightly decreased their arterial O2 tensions. Hypoxia increased and hyperoxia decreased their pulmonary vascular resistances. During O2 breathing, arterial PO2 was less during than before the pneumonia and increased when pulmonary perfusion was diverted away from the diseased lung. In 2 dogs breathing air, forcing the cardiac output through the diseased lung caused an increase in vascular resistance that could clearly be reduced by O2 breathing. In 5 dogs, lung mast cell counts showed no decrease in the lobes with pneumonia. In pneumococcal pneumonia, the hypoxic pulmonary pressor mechanism serves to decrease blood flow to the diseased lobes and, thus, to maintain the arterial PO2. Lung mast cells could participate in this response.", "contents": "Preservation of hypoxic pulmonary pressor response in canine pneumococcal pneumonia. To determine the role of hypoxic pulmonary vasoconstriction in pneumococcal pneumonia, hemodynamic measurements were made in 16 dogs before, and within 36 hours after, intrapulmonary administration of type III pneumococcus. Ten dogs with one lobe or more of pneumonia increased their pulmonary vascular resistances and slightly decreased their arterial O2 tensions. Hypoxia increased and hyperoxia decreased their pulmonary vascular resistances. During O2 breathing, arterial PO2 was less during than before the pneumonia and increased when pulmonary perfusion was diverted away from the diseased lung. In 2 dogs breathing air, forcing the cardiac output through the diseased lung caused an increase in vascular resistance that could clearly be reduced by O2 breathing. In 5 dogs, lung mast cell counts showed no decrease in the lobes with pneumonia. In pneumococcal pneumonia, the hypoxic pulmonary pressor mechanism serves to decrease blood flow to the diseased lobes and, thus, to maintain the arterial PO2. Lung mast cells could participate in this response."}
{"id": "PMID:936", "title": "Value of capillary blood gas analyses in the management of acute respiratory distress.", "content": "A comparative study of blood gases and acid-base parameters, obtained simultaneously from arterial and finger capillary samples, was performed in 45 patients in acute respiratory distress without circulatory shock. Although small and significant differences were found between the 2 sample pH, Po2, Pco2, and bicarbonate values, the correlations between the 2 were greater than or equal to 0.97 for each variable. It was concluded that although the arterial blood is the preferred sample for evaluation of blood gases and acid-base status of patients in acute respiratory distress, capillary blood appears to be a valid substitute in the management of these patients. This technique is particularly valuable in pediatric practice, where repeated arterial samples are less easily obtained.", "contents": "Value of capillary blood gas analyses in the management of acute respiratory distress. A comparative study of blood gases and acid-base parameters, obtained simultaneously from arterial and finger capillary samples, was performed in 45 patients in acute respiratory distress without circulatory shock. Although small and significant differences were found between the 2 sample pH, Po2, Pco2, and bicarbonate values, the correlations between the 2 were greater than or equal to 0.97 for each variable. It was concluded that although the arterial blood is the preferred sample for evaluation of blood gases and acid-base status of patients in acute respiratory distress, capillary blood appears to be a valid substitute in the management of these patients. This technique is particularly valuable in pediatric practice, where repeated arterial samples are less easily obtained."}
{"id": "PMID:937", "title": "Bone marrow transplantation in man.", "content": "Bone marrow transplantation is emerging as a viable therapeutic approach to a number of diseases that are usually or uniformly fatal. We review here recent experiences in bone marrow transplantation in man at UCLA and in various other institutions throughout the world. We examine marrow transplantation in immunodeficiency diseases, acute leukemia, and aplastic anemia and consider the problems of infection in the transplant recipients. The applications of tissue typing to marrow transplantation and immunologic manipulations, which may influence engraftment and graft-versus-host disease, are also reported.", "contents": "Bone marrow transplantation in man. Bone marrow transplantation is emerging as a viable therapeutic approach to a number of diseases that are usually or uniformly fatal. We review here recent experiences in bone marrow transplantation in man at UCLA and in various other institutions throughout the world. We examine marrow transplantation in immunodeficiency diseases, acute leukemia, and aplastic anemia and consider the problems of infection in the transplant recipients. The applications of tissue typing to marrow transplantation and immunologic manipulations, which may influence engraftment and graft-versus-host disease, are also reported."}
{"id": "PMID:938", "title": "The virus hypothesis in systemic lupus erythematosus.", "content": "Type-C viruses are currently the prime etiologic candidates in systemic lupus erythematosus. On the basis of knowledge gained from studies of experimental and human models of chronic viral disease, there are possible pathogenetic roles of a virus in systemic lupus erythematosus. Experimental attempts at implicating specific viruses have been predominantly negative, but evidence for enhanced type-C-virus expression has recently been reported.", "contents": "The virus hypothesis in systemic lupus erythematosus. Type-C viruses are currently the prime etiologic candidates in systemic lupus erythematosus. On the basis of knowledge gained from studies of experimental and human models of chronic viral disease, there are possible pathogenetic roles of a virus in systemic lupus erythematosus. Experimental attempts at implicating specific viruses have been predominantly negative, but evidence for enhanced type-C-virus expression has recently been reported."}
{"id": "PMID:944", "title": "The membrane transport of ascorbic acid.", "content": "A system for measuring the rate of transport of dehydroascorbate into human red blood cells shows Michaelis-Menten type kinetics with substrate inhibition at levels above 150 muM DHA. The addition of sugars impairs this transport in the diminishing hierarchy D-glucose, D-mannose, D-xylose, D-galactose, L-lyxose, D-araboascorbate, L-sorbose and 2-deoxy-D-ribose. The effect of glucose on transport of ascorbate is marked at physiological levels. Transport of DHA is accelerated by copper ion and allows dehydroascorbate to move against a concentration gradient. The evidence supports the hypotheses proposing that hyperglycemia will impair the intracellular availability of vitamin C.", "contents": "The membrane transport of ascorbic acid. A system for measuring the rate of transport of dehydroascorbate into human red blood cells shows Michaelis-Menten type kinetics with substrate inhibition at levels above 150 muM DHA. The addition of sugars impairs this transport in the diminishing hierarchy D-glucose, D-mannose, D-xylose, D-galactose, L-lyxose, D-araboascorbate, L-sorbose and 2-deoxy-D-ribose. The effect of glucose on transport of ascorbate is marked at physiological levels. Transport of DHA is accelerated by copper ion and allows dehydroascorbate to move against a concentration gradient. The evidence supports the hypotheses proposing that hyperglycemia will impair the intracellular availability of vitamin C."}
{"id": "PMID:947", "title": "Carcinofetal alterations in glucosamine-6-phosphate synthetase.", "content": "The levels of glucosamine-6-phosphate synthetase in various rat tissues including those undergoing differentiation or regeneration revealed that the enzyme is related to tissue proliferation and differentiation. In the liver upon neoplastic transformation, the level of glucosamine 6-phosphate synthetase rises and the liver form of the enzyme having a pI at 5.0 is replaced by a form with a pI of 4.1. Since the latter form has also been found present in whole embryos (12- and 14-day) and brain, the molecular alterations of glucosamine-6-phosphate synthetase in liver neoplasia can be considered to be carcinofetal.", "contents": "Carcinofetal alterations in glucosamine-6-phosphate synthetase. The levels of glucosamine-6-phosphate synthetase in various rat tissues including those undergoing differentiation or regeneration revealed that the enzyme is related to tissue proliferation and differentiation. In the liver upon neoplastic transformation, the level of glucosamine 6-phosphate synthetase rises and the liver form of the enzyme having a pI at 5.0 is replaced by a form with a pI of 4.1. Since the latter form has also been found present in whole embryos (12- and 14-day) and brain, the molecular alterations of glucosamine-6-phosphate synthetase in liver neoplasia can be considered to be carcinofetal."}
{"id": "PMID:948", "title": "A hepatoma-associated alkaline phosphatase, the Kasahara isozyme, compared with one of the isozymes of FL amnion cells.", "content": "It was found that a human hepatoma-associated ALP (orthophosphoric monoester phosphohydrolase, E.C. 3.1.3.1) shared electrophoretic mobility, inactivation by urea, inhibition by inorganic phosphate, ethylenediaminetetraacetate, and amino acids (L-phenylalanine, L-leucine and L-homoarginine), heat stability, sensitivity to neuraminidase, pH optimum, Km value, and antigen site with fast moving ALP isozymes of FL cell strain derived from human amniotic membrane. However, 40-week-old fresh amniotic membrane lacked this isozyme. Instead, it had a placental type ALP consisting of minor components. The other ALP isozyme of FL cells had properties common to hepatoma ALP with regard to L-phenylalanine sensitivity, inhibition by ethylenediaminetetraacetate, inactivation by urea, and antigen site, but differed from it in electrophoretic mobility, sensitivity to L-leucine and L-homoarginine, and the presence of another antigen site. It was more heat stable and more sensitive to inhibition by inorganic phosphate than Hepatoma AP. The possible regulatory mechanism between the hepatoma-type ALP and the placental type ALP in the amnion cells is considered.", "contents": "A hepatoma-associated alkaline phosphatase, the Kasahara isozyme, compared with one of the isozymes of FL amnion cells. It was found that a human hepatoma-associated ALP (orthophosphoric monoester phosphohydrolase, E.C. 3.1.3.1) shared electrophoretic mobility, inactivation by urea, inhibition by inorganic phosphate, ethylenediaminetetraacetate, and amino acids (L-phenylalanine, L-leucine and L-homoarginine), heat stability, sensitivity to neuraminidase, pH optimum, Km value, and antigen site with fast moving ALP isozymes of FL cell strain derived from human amniotic membrane. However, 40-week-old fresh amniotic membrane lacked this isozyme. Instead, it had a placental type ALP consisting of minor components. The other ALP isozyme of FL cells had properties common to hepatoma ALP with regard to L-phenylalanine sensitivity, inhibition by ethylenediaminetetraacetate, inactivation by urea, and antigen site, but differed from it in electrophoretic mobility, sensitivity to L-leucine and L-homoarginine, and the presence of another antigen site. It was more heat stable and more sensitive to inhibition by inorganic phosphate than Hepatoma AP. The possible regulatory mechanism between the hepatoma-type ALP and the placental type ALP in the amnion cells is considered."}
{"id": "PMID:949", "title": "Gamma-glutamyl transpeptidase. A sensitive indicator  of renal ischaemic injury in experimental animals and renal homograft rejection in man.", "content": "The sites of ischaemic injury within the kidney are reviewed and the diagnostic value of measurements of plasma and urinary enzymes in renal ischaemic injury and in renal homotransplant rejection in experimental animals and man is examined. Gamma-glutamyl transpeptidase (gamma-GT) is an enzyme primarily located in the brush border of the proximal convoluted tubule of the kidney. Its unique localization in the cells most easily damaged by ischaemia and its ease of assay provide the rationale for its use in the measurement and diagnosis of renal ischaemic injury. gamma-GT activity was measured in dogs undergoing varying periods of renal ischaemia and under conditions of local renal hypothermia and was shown to be a sensitive indicator of ischaemic injury. Twenty consecutive patients undergoing renal homotransplantation were studied by daily estimation of their 24-h urinary gamma-GT activity; excellent correlation was obtained between raised levels of this enzyme and the clinical diagnosis of transplant rejection.", "contents": "Gamma-glutamyl transpeptidase. A sensitive indicator  of renal ischaemic injury in experimental animals and renal homograft rejection in man. The sites of ischaemic injury within the kidney are reviewed and the diagnostic value of measurements of plasma and urinary enzymes in renal ischaemic injury and in renal homotransplant rejection in experimental animals and man is examined. Gamma-glutamyl transpeptidase (gamma-GT) is an enzyme primarily located in the brush border of the proximal convoluted tubule of the kidney. Its unique localization in the cells most easily damaged by ischaemia and its ease of assay provide the rationale for its use in the measurement and diagnosis of renal ischaemic injury. gamma-GT activity was measured in dogs undergoing varying periods of renal ischaemia and under conditions of local renal hypothermia and was shown to be a sensitive indicator of ischaemic injury. Twenty consecutive patients undergoing renal homotransplantation were studied by daily estimation of their 24-h urinary gamma-GT activity; excellent correlation was obtained between raised levels of this enzyme and the clinical diagnosis of transplant rejection."}
{"id": "PMID:950", "title": "Influence of pH on the heat inactivation of staphylococcal enterotoxin A as determined by monkey feeding and serological assay.", "content": "The effect of pH on the thermal inactivation of staphylococcal enterotoxin A was investigated. Analysis of heated toxin by immunodiffusion in gel indicated that enterotoxin A in beef bouillon was inactivated faster at pH 5.3 than at pH 6.2. The z values (slopes) for the heat inactivation curves at pH 6.2 and 5.3 were 49.5 and 55 F (about 27 and 30 C), respectively. Enterotoxin produced and heated in dialyzed Casamino Acids medium and assayed by monkey feeding was more easily inactivated by heat at pH 5.3 than at pH 7.8. Thermal inactivation curves for enterotoxin A in beef bouillon (5 mug/ml, pH 5.3) were determined by two methods, monkey feeding and serological assay. The z values for the curves obtained by these two methods were both 55 F, although loss of biological or toxic activity of the enterotoxin occurred before loss of serological activity.", "contents": "Influence of pH on the heat inactivation of staphylococcal enterotoxin A as determined by monkey feeding and serological assay. The effect of pH on the thermal inactivation of staphylococcal enterotoxin A was investigated. Analysis of heated toxin by immunodiffusion in gel indicated that enterotoxin A in beef bouillon was inactivated faster at pH 5.3 than at pH 6.2. The z values (slopes) for the heat inactivation curves at pH 6.2 and 5.3 were 49.5 and 55 F (about 27 and 30 C), respectively. Enterotoxin produced and heated in dialyzed Casamino Acids medium and assayed by monkey feeding was more easily inactivated by heat at pH 5.3 than at pH 7.8. Thermal inactivation curves for enterotoxin A in beef bouillon (5 mug/ml, pH 5.3) were determined by two methods, monkey feeding and serological assay. The z values for the curves obtained by these two methods were both 55 F, although loss of biological or toxic activity of the enterotoxin occurred before loss of serological activity."}
{"id": "PMID:951", "title": "Survival of salmonellae during pepperoni manufacture.", "content": "Survival of salmonellae in artificially contaminated beef-pork mixtures (approximately 10(4) salmonellae/g) was studied in pepperoni prepared by either a natural flora or lactic starter culture fermentation or in nonfermented sausages. The pepperoni did not become salmonellae free during the usual commercial 15 to 30-day drying period. Salmonella dublin was present in all products, fermented or unfermented, after 42 to 43 days of drying. At a lower level of contamination, 10(3)/g, S. dublin could not be recovered from starter culture-fermented pepperoni after 14 days of drying but persisted in the natural flora-fermented sausage. S. typhimurium (initial count, 10(4)/g) was absent after 42 days of drying when starter culture was used to ferment the pepperoni, but was still present in the natural flora-fermented and unfermented products. S. dublin, host adapted to cattle, or S. choleraesuis, host adapted to swine, had similar  survival patterns in beef pork, or beef-pork pepperoni. Heating salmonellae contaminated beef-pork pepperoni (after fermantation but before drying) to an internal temperature of 60 C (trichinae inactivating) eliminated the food-borne pathogen from the sausage product.", "contents": "Survival of salmonellae during pepperoni manufacture. Survival of salmonellae in artificially contaminated beef-pork mixtures (approximately 10(4) salmonellae/g) was studied in pepperoni prepared by either a natural flora or lactic starter culture fermentation or in nonfermented sausages. The pepperoni did not become salmonellae free during the usual commercial 15 to 30-day drying period. Salmonella dublin was present in all products, fermented or unfermented, after 42 to 43 days of drying. At a lower level of contamination, 10(3)/g, S. dublin could not be recovered from starter culture-fermented pepperoni after 14 days of drying but persisted in the natural flora-fermented sausage. S. typhimurium (initial count, 10(4)/g) was absent after 42 days of drying when starter culture was used to ferment the pepperoni, but was still present in the natural flora-fermented and unfermented products. S. dublin, host adapted to cattle, or S. choleraesuis, host adapted to swine, had similar  survival patterns in beef pork, or beef-pork pepperoni. Heating salmonellae contaminated beef-pork pepperoni (after fermantation but before drying) to an internal temperature of 60 C (trichinae inactivating) eliminated the food-borne pathogen from the sausage product."}
{"id": "PMID:952", "title": "Growth of Staphylococcus and Salmonella on frankfurters with and without sodium nitrite.", "content": "Conventional and nitrite-free frankfurters in loosely wrapped packages were compared as to their ability to support growth of Salmonella, Staphylococcus, and their naturally occurring spoilage flora at 7 C (simulating refrigerated  storage) and 20 C (simulating possible temperature abuse). At 7 C Salmonella did not grow in either type of frankfurter; Staphylococcus and the natural spoilage flora sometimes grew more rapidly in the absence of nitrite, but the difference was not significant. At 20 C growth of Salmonella, Staphylococcus, and of the spoilage flora was, at most, only slightly faster on nitrite-free frankfurters. Salmonella was not suppressed in broth culture experiments the pH and nitrite content found in frankfurters. Although either type of frankfurter can become hazardous due to growth of Salmonella or Staphylococcus, no unusual or additional hazard resulted from the omission of nitrite from frankfurters.", "contents": "Growth of Staphylococcus and Salmonella on frankfurters with and without sodium nitrite. Conventional and nitrite-free frankfurters in loosely wrapped packages were compared as to their ability to support growth of Salmonella, Staphylococcus, and their naturally occurring spoilage flora at 7 C (simulating refrigerated  storage) and 20 C (simulating possible temperature abuse). At 7 C Salmonella did not grow in either type of frankfurter; Staphylococcus and the natural spoilage flora sometimes grew more rapidly in the absence of nitrite, but the difference was not significant. At 20 C growth of Salmonella, Staphylococcus, and of the spoilage flora was, at most, only slightly faster on nitrite-free frankfurters. Salmonella was not suppressed in broth culture experiments the pH and nitrite content found in frankfurters. Although either type of frankfurter can become hazardous due to growth of Salmonella or Staphylococcus, no unusual or additional hazard resulted from the omission of nitrite from frankfurters."}
{"id": "PMID:953", "title": "Characterization of an extracellular dextranase from Fusarium moniliforme.", "content": "An extracellular dextranase (EC 3.2.1.11) was purified approximately 75-fold from cell-free culture filtrates of Fusarium moniliforme. The purified dextranase was of the endo type, and isomaltose was identified as the primary end product of dextran hydrolysis. The molecular weight of the dextranase was determined to be 39,000 by gel permeation chromatography. The enzyme was most active at pH 5.5, and the temperature optimum was near 55 C. Activity was not inhibited by either ethylenediaminetetraacetic acid or iodoacetate. The Km for dextran with an average molecular weight of 10,000 was estimated to be 1.1 X 10(-4) M. The electrophoretic mobility of the dextranase was distinctly different from that of a Penicillium-derived commercial dextranase. The F. moniliforme dextranase was also found to differ from the commercial preparation by its greater relative activity against glucans isolated from Streptococcus mutans.", "contents": "Characterization of an extracellular dextranase from Fusarium moniliforme. An extracellular dextranase (EC 3.2.1.11) was purified approximately 75-fold from cell-free culture filtrates of Fusarium moniliforme. The purified dextranase was of the endo type, and isomaltose was identified as the primary end product of dextran hydrolysis. The molecular weight of the dextranase was determined to be 39,000 by gel permeation chromatography. The enzyme was most active at pH 5.5, and the temperature optimum was near 55 C. Activity was not inhibited by either ethylenediaminetetraacetic acid or iodoacetate. The Km for dextran with an average molecular weight of 10,000 was estimated to be 1.1 X 10(-4) M. The electrophoretic mobility of the dextranase was distinctly different from that of a Penicillium-derived commercial dextranase. The F. moniliforme dextranase was also found to differ from the commercial preparation by its greater relative activity against glucans isolated from Streptococcus mutans."}
{"id": "PMID:954", "title": "Nonautotrophic Thiobacillus in acid mine water.", "content": "Nonautotrophic thiobacilli were isolated from the acidic water of a coal mine. Based on their mixotrophic physiology, the isolates are regarded as strains of Thiobacillus perometabolis.", "contents": "Nonautotrophic Thiobacillus in acid mine water. Nonautotrophic thiobacilli were isolated from the acidic water of a coal mine. Based on their mixotrophic physiology, the isolates are regarded as strains of Thiobacillus perometabolis."}
{"id": "PMID:972", "title": "Graft versus host reaction. An ultrastructural study.", "content": "Graft versus host reaction (GvH) following leukocytic transfusions occurred in a 34-year-old man with a generalized lymphosarcoma. Histologic and ultrastructural studies were performed, with special reference to dyskeratotic cells scattered in the epidermis. These cells are usually considered to be a constant and important feature of GvH reaction. Dense aggregation of tonofilaments, including cytoplasmic organelles and loss of desmosomes, were seen in dyskeratotic cells. Several intracellular desmosomes with tonofilaments bound to their attachment plaque were observed. Some of these cells were able to reach the horny layer; some others were phagocytosed by neighboring keratinocytes. These cells could be the result of a toxic damage to the epidermis, provoked by the immunologic phenomenon implicated in GvH reaction. Later in the clinical course, bullae formations occurred, showing some features of toxic epidermal necrolysis (TEN), as well as features of GvH reaction.", "contents": "Graft versus host reaction. An ultrastructural study. Graft versus host reaction (GvH) following leukocytic transfusions occurred in a 34-year-old man with a generalized lymphosarcoma. Histologic and ultrastructural studies were performed, with special reference to dyskeratotic cells scattered in the epidermis. These cells are usually considered to be a constant and important feature of GvH reaction. Dense aggregation of tonofilaments, including cytoplasmic organelles and loss of desmosomes, were seen in dyskeratotic cells. Several intracellular desmosomes with tonofilaments bound to their attachment plaque were observed. Some of these cells were able to reach the horny layer; some others were phagocytosed by neighboring keratinocytes. These cells could be the result of a toxic damage to the epidermis, provoked by the immunologic phenomenon implicated in GvH reaction. Later in the clinical course, bullae formations occurred, showing some features of toxic epidermal necrolysis (TEN), as well as features of GvH reaction."}
{"id": "PMID:973", "title": "Nephrotic syndrome in indian children.", "content": "A clinicopathological study of 206 Indian children with nephrotic syndrome showed a primary renal cause in 195 (96%), of which 77% were boys. In 126 children (96 boys, 30 girls) onset of the disorder occurred before the age of 5 years. Renal biopsy showed minimal lesions in 150 patients (77%); in 85 of these biopsy was done 3 months to 16 years after onset of the nephrotic syndrome. Significant renal histological abnormalities in 45 cases were labelled as mesangiocapillary 8, mesangioproliferative 4, proliferative with extensive crescents 2, membranous 3, focal segmental glomerulosclerosis 9, focal global glomerulosclerosis 2, advanced nonspecific 8, and mild proliferative 9. Nephritic manifestations were mainly associated with significant renal lesions, which were more frequently encountered when the onset of disease was after the age of 5 years. Clearance of proteinuria with corticosteroid therapy was practically confined to patients with minimal or mild renal histological changes. Our findings suggest that the pattern of idiopathic nephrotic syndrome in Indian children is similar to that reported from Western countries.", "contents": "Nephrotic syndrome in indian children. A clinicopathological study of 206 Indian children with nephrotic syndrome showed a primary renal cause in 195 (96%), of which 77% were boys. In 126 children (96 boys, 30 girls) onset of the disorder occurred before the age of 5 years. Renal biopsy showed minimal lesions in 150 patients (77%); in 85 of these biopsy was done 3 months to 16 years after onset of the nephrotic syndrome. Significant renal histological abnormalities in 45 cases were labelled as mesangiocapillary 8, mesangioproliferative 4, proliferative with extensive crescents 2, membranous 3, focal segmental glomerulosclerosis 9, focal global glomerulosclerosis 2, advanced nonspecific 8, and mild proliferative 9. Nephritic manifestations were mainly associated with significant renal lesions, which were more frequently encountered when the onset of disease was after the age of 5 years. Clearance of proteinuria with corticosteroid therapy was practically confined to patients with minimal or mild renal histological changes. Our findings suggest that the pattern of idiopathic nephrotic syndrome in Indian children is similar to that reported from Western countries."}
{"id": "PMID:974", "title": "Separation of deoxyribonucleases (DNases) of normal human stratum corneum and psoriatic scales by micro-disc-electrophoresis.", "content": "Normal stratum corneum and psoriatic scales were homogenized and a differential centrifugation was performed. The DNase activity of the individual fractions was investigated by micro-dis-electrophoresis. At pH 5 only in the 600xg pellet and 105.000xg supernatant of normal keratin DNase activity could be observed. However, all psoriatic fractions showed distinct enzyme activities. At pH 7.4 little psoriatic DNase activity could only be demonstrated in the 105.000xg supernatant. Except from the 15.000xg pellet all fractions of normal stratum corneum displayed marked activities. In addition the 105.000xg supernatant showed two different DNase bands.", "contents": "Separation of deoxyribonucleases (DNases) of normal human stratum corneum and psoriatic scales by micro-disc-electrophoresis. Normal stratum corneum and psoriatic scales were homogenized and a differential centrifugation was performed. The DNase activity of the individual fractions was investigated by micro-dis-electrophoresis. At pH 5 only in the 600xg pellet and 105.000xg supernatant of normal keratin DNase activity could be observed. However, all psoriatic fractions showed distinct enzyme activities. At pH 7.4 little psoriatic DNase activity could only be demonstrated in the 105.000xg supernatant. Except from the 15.000xg pellet all fractions of normal stratum corneum displayed marked activities. In addition the 105.000xg supernatant showed two different DNase bands."}
{"id": "PMID:975", "title": "Subcellular distribution of phosphatases, proteinases, and ribonucleases in normal human stratum corneum and psoriatic scales.", "content": "The subcellular distribution of phosphatases, proteinases, and ribonucleases of normal human stratum corneum and psoriatic scales was determined after differential centrifugation. All psoriatic enzymes showed much increased activities as compared to the normal stratum corneum enzymes. The highest activities of alkaline phosphatase from psoriatic scales could be detected in the nuclear fraction. The main activities of all other tested phosphatases and proteinases were present in the cytoplasmatic fraction. The subcellular distribution of the ribonucleases varied according to the pH value.", "contents": "Subcellular distribution of phosphatases, proteinases, and ribonucleases in normal human stratum corneum and psoriatic scales. The subcellular distribution of phosphatases, proteinases, and ribonucleases of normal human stratum corneum and psoriatic scales was determined after differential centrifugation. All psoriatic enzymes showed much increased activities as compared to the normal stratum corneum enzymes. The highest activities of alkaline phosphatase from psoriatic scales could be detected in the nuclear fraction. The main activities of all other tested phosphatases and proteinases were present in the cytoplasmatic fraction. The subcellular distribution of the ribonucleases varied according to the pH value."}
{"id": "PMID:976", "title": "A reinvestigation of the sites of transcription and translation of Euglena chloroplastic phenylalanyl-tRNA synthetase.", "content": "An attempt was made to determine the sites of chloroplast phenylalanyl-tRNA synthetase transcription and translation. Inhibitors of bacterial RNA and protein synthesis were added to logarithmic and stationary phase cultures of Euglena gracilis wild-type B. Logarithmic phase cultures were sensitive to both types of inhibitors. In stationary phase cultures plastid synthetase was reduced by RNA but not by protein synthesis inhibitors. The effect of the antibiotics on the mitochondrial enzyme was also noted. Several possible explanations of these resuults are discussed.", "contents": "A reinvestigation of the sites of transcription and translation of Euglena chloroplastic phenylalanyl-tRNA synthetase. An attempt was made to determine the sites of chloroplast phenylalanyl-tRNA synthetase transcription and translation. Inhibitors of bacterial RNA and protein synthesis were added to logarithmic and stationary phase cultures of Euglena gracilis wild-type B. Logarithmic phase cultures were sensitive to both types of inhibitors. In stationary phase cultures plastid synthetase was reduced by RNA but not by protein synthesis inhibitors. The effect of the antibiotics on the mitochondrial enzyme was also noted. Several possible explanations of these resuults are discussed."}
{"id": "PMID:977", "title": "[Hyperthermia in the rabbit. II. Studies on influencing respiration with exogenic hyperthermia].", "content": "Rectal temperature, respiratory rate, arterial and venous pH and arterial and venous pCO2 were recorded at intervals of 15-30 minutes in female broiler rabbits exposed an environmental temperature of 35 degrees C, until they died. Respiratory rate and blood pH rose, and pCO2 fell, until a rectal temperature of 42 degrees C was reached. Upon further increase in rectal temperature the respiratory rate and pH began to fall, while pCO2 began to rise. The rabbits died when rectal temperature reached 43 degrees C. Features of respiratory function peculiar to the rabbit were discussed.", "contents": "[Hyperthermia in the rabbit. II. Studies on influencing respiration with exogenic hyperthermia]. Rectal temperature, respiratory rate, arterial and venous pH and arterial and venous pCO2 were recorded at intervals of 15-30 minutes in female broiler rabbits exposed an environmental temperature of 35 degrees C, until they died. Respiratory rate and blood pH rose, and pCO2 fell, until a rectal temperature of 42 degrees C was reached. Upon further increase in rectal temperature the respiratory rate and pH began to fall, while pCO2 began to rise. The rabbits died when rectal temperature reached 43 degrees C. Features of respiratory function peculiar to the rabbit were discussed."}
{"id": "PMID:978", "title": "Outpatient phenothiazine use and bone marrow depression. A report from the drug epidemiology unit and the Boston collaborative drug surveillance program.", "content": "Phenothiazine-induced bone marrow depression (BMD) was evaluated in three separate but complementary data bases: (1) Among 1,048 patients admitted to psychiatric hospitals, there was no evidence of subclinical depression of the white blood cell (WBC) count attributable to phenothiazines used before admission. (2) Among 18,587 medical inpatients, there were 34 patients admitted for BMD in the absence of neoplasia or prior cytotoxic drug therapy; one of the latter reported using chlorpromazine hydrochloride, but it is doubtful whether this drug was the cause of the BMD. (3) Among 24,795 medical, surgical, and gynecological patients surveyed over a ten-month period in 1972, there were four who were admitted for BMD; one of the latter had a reversible leukopenia attributed to trifluoperazine hydrochloride.", "contents": "Outpatient phenothiazine use and bone marrow depression. A report from the drug epidemiology unit and the Boston collaborative drug surveillance program. Phenothiazine-induced bone marrow depression (BMD) was evaluated in three separate but complementary data bases: (1) Among 1,048 patients admitted to psychiatric hospitals, there was no evidence of subclinical depression of the white blood cell (WBC) count attributable to phenothiazines used before admission. (2) Among 18,587 medical inpatients, there were 34 patients admitted for BMD in the absence of neoplasia or prior cytotoxic drug therapy; one of the latter reported using chlorpromazine hydrochloride, but it is doubtful whether this drug was the cause of the BMD. (3) Among 24,795 medical, surgical, and gynecological patients surveyed over a ten-month period in 1972, there were four who were admitted for BMD; one of the latter had a reversible leukopenia attributed to trifluoperazine hydrochloride."}
{"id": "PMID:979", "title": "[Tumour hyperacidulation through intravenous glucose infusion enhanced by amygdalin and beta-glucosidase application (author's transl)].", "content": "Tumour peracidity in otherwise moderately hyperacidulated tumours or tumour regions of DS carcinosarcoma-bearing Wistar rats attained by glucose infusion was substantially increased by simultaneous infusion of amygdalin and intratumoral i.m. or i.v. application of beta-glucosidase. Here the pH value of healthy tissue, measured at the sceletal muscle, remained unchanged. By means of the said process, tumour hyperacidulation has been raised to a level of deltapH =0.97; attaining a pH difference between tumourous and normal tissue of up to deltapH = 1.6. In one case, the slope of pH reduction in the tumour increased to 870%. Moreover, combined administration of glucose, amygdalin and beta-glucosidase evoked a significant cancerostatic effect hypogenesis, tumour regression) being comparable with the action of an Ifosfamid dosage of 150 mg-kg-1. However, i.m. and i.v. application of beta-glucosidase under narcosis results in an overall process that still remains somewhat too toxic. Hence optimizing studies are intended with the particular aim to further improve the comparability of this process.", "contents": "[Tumour hyperacidulation through intravenous glucose infusion enhanced by amygdalin and beta-glucosidase application (author's transl)]. Tumour peracidity in otherwise moderately hyperacidulated tumours or tumour regions of DS carcinosarcoma-bearing Wistar rats attained by glucose infusion was substantially increased by simultaneous infusion of amygdalin and intratumoral i.m. or i.v. application of beta-glucosidase. Here the pH value of healthy tissue, measured at the sceletal muscle, remained unchanged. By means of the said process, tumour hyperacidulation has been raised to a level of deltapH =0.97; attaining a pH difference between tumourous and normal tissue of up to deltapH = 1.6. In one case, the slope of pH reduction in the tumour increased to 870%. Moreover, combined administration of glucose, amygdalin and beta-glucosidase evoked a significant cancerostatic effect hypogenesis, tumour regression) being comparable with the action of an Ifosfamid dosage of 150 mg-kg-1. However, i.m. and i.v. application of beta-glucosidase under narcosis results in an overall process that still remains somewhat too toxic. Hence optimizing studies are intended with the particular aim to further improve the comparability of this process."}
{"id": "PMID:981", "title": "Studies of the pain produced by mafenide acetate preparations in burns.", "content": "In a double-blind triple cross-over clinical study, 37 patients were exposed to several formulations of mafenide acetate (Sulfamylon Cream) and their pain responses were recorded and converted to a semiquantitative pain index. The 11.2% concentration in cream was two to three times more painful than the 5% concentration. Hypertonicity  and not the pH level appears to be the cause of the pain produced by the high (11.2%) concentration. The tonicity of the cream carrier and 11.2% mafenide acetate are 1,080 mOsm/kg and 1,100 mOsm/kg, respectively, for a total of 2,180 mOsm/kg. The carrier cream without glycerol and a 5% concentration of mafenide cream were much less painful than the 11.2% concentration of mafenide. Both afforded a great deal of relief to the patients who received the medications.", "contents": "Studies of the pain produced by mafenide acetate preparations in burns. In a double-blind triple cross-over clinical study, 37 patients were exposed to several formulations of mafenide acetate (Sulfamylon Cream) and their pain responses were recorded and converted to a semiquantitative pain index. The 11.2% concentration in cream was two to three times more painful than the 5% concentration. Hypertonicity  and not the pH level appears to be the cause of the pain produced by the high (11.2%) concentration. The tonicity of the cream carrier and 11.2% mafenide acetate are 1,080 mOsm/kg and 1,100 mOsm/kg, respectively, for a total of 2,180 mOsm/kg. The carrier cream without glycerol and a 5% concentration of mafenide cream were much less painful than the 11.2% concentration of mafenide. Both afforded a great deal of relief to the patients who received the medications."}
{"id": "PMID:982", "title": "Microbiol growth in lipid emulsions used in parenteral nutrition.", "content": "Parenteral nutrition via central venous catheterization is associated with serious risks, especially that of sepsis. Lipid emulsion (Intralipid[Sweden]), which may be administered peripherally, was evaluated for its potential to support microbial growth. Washed cultures of Staphylococcus aureus, Candida albicans, and three species of Gram-negative rods were all capable of multiplying in the emulsion at room temperature. Variations in inoculum size did not affect the growth rate. Studies comparing the emulsion to amino acid-glucose solutions (total parenteral nutrition [TPN])confirmed other reports that TPN inhibits the growth of certain bacteria but merely retards fungal multiplication. When human serum was added to the lipid emulsion in an attempt to simulate in vivo conditions at the catheter tip, Escherichia coli was inhibited while the growth of S aureus and C albicians was unaltered.", "contents": "Microbiol growth in lipid emulsions used in parenteral nutrition. Parenteral nutrition via central venous catheterization is associated with serious risks, especially that of sepsis. Lipid emulsion (Intralipid[Sweden]), which may be administered peripherally, was evaluated for its potential to support microbial growth. Washed cultures of Staphylococcus aureus, Candida albicans, and three species of Gram-negative rods were all capable of multiplying in the emulsion at room temperature. Variations in inoculum size did not affect the growth rate. Studies comparing the emulsion to amino acid-glucose solutions (total parenteral nutrition [TPN])confirmed other reports that TPN inhibits the growth of certain bacteria but merely retards fungal multiplication. When human serum was added to the lipid emulsion in an attempt to simulate in vivo conditions at the catheter tip, Escherichia coli was inhibited while the growth of S aureus and C albicians was unaltered."}
{"id": "PMID:983", "title": "Propoxyphene and norpropoxyphene tissue concentrations in fatalities associated with propoxyphene hydrochloride and propoxyphene napsylate.", "content": "Propoxyphene and its major metabolite norpropoxyphene have been determined in blood and liver in 29 cases of death in which propoxyphene, either as the hydrochloride or as the napsylate salt, was involved. The use of propoxyphene napsylate (Darvon-N) contributed to the deaths of 4 persons, 3 of whom were former heroin addicts receiving large amounts of this drug in connection with propoxyphene substitution programs. In the majority of cases the norpropoxyphene blood concentrations exceed the propoxyphene concentrations, although brain determinations in several instances indicate that norpropoxyphene does not cross the blood-brain barrier with the same ease as propoxyphene. On the basis of the comparative toxicities of propoxyphene and norpropoxyphene in animals and the high tissue concentrations of norporpoxyphene in man after propoxyphene administration, it is conceivable that norpropoxyphene contributes to the toxic effects of propoxyphene.", "contents": "Propoxyphene and norpropoxyphene tissue concentrations in fatalities associated with propoxyphene hydrochloride and propoxyphene napsylate. Propoxyphene and its major metabolite norpropoxyphene have been determined in blood and liver in 29 cases of death in which propoxyphene, either as the hydrochloride or as the napsylate salt, was involved. The use of propoxyphene napsylate (Darvon-N) contributed to the deaths of 4 persons, 3 of whom were former heroin addicts receiving large amounts of this drug in connection with propoxyphene substitution programs. In the majority of cases the norpropoxyphene blood concentrations exceed the propoxyphene concentrations, although brain determinations in several instances indicate that norpropoxyphene does not cross the blood-brain barrier with the same ease as propoxyphene. On the basis of the comparative toxicities of propoxyphene and norpropoxyphene in animals and the high tissue concentrations of norporpoxyphene in man after propoxyphene administration, it is conceivable that norpropoxyphene contributes to the toxic effects of propoxyphene."}
{"id": "PMID:984", "title": "[Morphological manifestations and morphogenesis of the graft vs. host reaction in the brain of F1 hybrids following the administration of parental lymphoid cells and its effect on tumor inoculation].", "content": "It was established that intracerebral introduction of 10 min parental cells of the spleen brought about in hybrids (CBAXC57Bl/6) F1 infiltrative-destructive changes (development of lymphocytic infiltrations, dystrophy in the nerve cells, myelin fibres and neurogliacytes) the intensity of which was found to be considerably higher in cases of injection of parental spleen cells from specifically sensitized donors. Spleen cells of mice CBA produced much greater changes as compared with those produced by spleen cells of mice C57Bl/6. Inoculation into the mice brain of 10 mln of spleen cells together with tumour in a dose of 1500 cells produced a clear cut inhibitory effect on the tumour growth, this effect being more pronounced following introduction of sensitized cells of the spleen of mice CBA.", "contents": "[Morphological manifestations and morphogenesis of the graft vs. host reaction in the brain of F1 hybrids following the administration of parental lymphoid cells and its effect on tumor inoculation]. It was established that intracerebral introduction of 10 min parental cells of the spleen brought about in hybrids (CBAXC57Bl/6) F1 infiltrative-destructive changes (development of lymphocytic infiltrations, dystrophy in the nerve cells, myelin fibres and neurogliacytes) the intensity of which was found to be considerably higher in cases of injection of parental spleen cells from specifically sensitized donors. Spleen cells of mice CBA produced much greater changes as compared with those produced by spleen cells of mice C57Bl/6. Inoculation into the mice brain of 10 mln of spleen cells together with tumour in a dose of 1500 cells produced a clear cut inhibitory effect on the tumour growth, this effect being more pronounced following introduction of sensitized cells of the spleen of mice CBA."}
{"id": "PMID:985", "title": "Metachromatic leukodystrophy. Ultrastructural and enzymatic study of a case of variant O form.", "content": "A variant of metachromatic leukodystrophy (MLD), Austin disease, is characterized by a multiple isozyme deficiency of arylsulfatase. A 3 1/2-year-old girl with progressive mental and physical deterioration had decreased activities of arylsulfatases A and B in the leukocytes, shown by acylamide gel electrophoresis. Under the electron microscope, biopsy specimens of the brain and the peripheral nerve showed lamellar structures with socalled zebra bodies in the cytoplasmic processes of glial cells, granulo-membranous inclusions with fingerprint configurations in neurons, and myelinlike material in Schwann cells. Results from our study suggest an intricate nature of this dysmetabolic disorder, which shows ultrastructural changes usually seen in classic MLD, a deficiency of arylsulfatase A only, concomitant with those seen in mucopolysaccharidoses such as Hurler and Sanfilippo syndromes.", "contents": "Metachromatic leukodystrophy. Ultrastructural and enzymatic study of a case of variant O form. A variant of metachromatic leukodystrophy (MLD), Austin disease, is characterized by a multiple isozyme deficiency of arylsulfatase. A 3 1/2-year-old girl with progressive mental and physical deterioration had decreased activities of arylsulfatases A and B in the leukocytes, shown by acylamide gel electrophoresis. Under the electron microscope, biopsy specimens of the brain and the peripheral nerve showed lamellar structures with socalled zebra bodies in the cytoplasmic processes of glial cells, granulo-membranous inclusions with fingerprint configurations in neurons, and myelinlike material in Schwann cells. Results from our study suggest an intricate nature of this dysmetabolic disorder, which shows ultrastructural changes usually seen in classic MLD, a deficiency of arylsulfatase A only, concomitant with those seen in mucopolysaccharidoses such as Hurler and Sanfilippo syndromes."}
{"id": "PMID:986", "title": "Changes in the acid base status of sheep anaesthetised with a combination of atropine sulphate acepromazine and ketamine hydrochloride.", "content": "pH, PaCO2, PaO2, standard bicarbonate, base excess and reduced pH were measured in sheep before and at regular intervals after administration of ketamine with and without atropine and acepromazine premedication. A decrease in pH and PaO2 and a rise in PaCO2 was observed 15 minutes after administration of ketamine. Administration of atropine with and without acepromazine had no significant effect on pH, PaCO2 and PaO2. The values for standard bicarbonate, base excess and reduced pH were not significantly affected. This indicates that minor changes observed in pH, PaCO2 after ketamine administration are compensated for by the healthy animal's blood buffer system.", "contents": "Changes in the acid base status of sheep anaesthetised with a combination of atropine sulphate acepromazine and ketamine hydrochloride. pH, PaCO2, PaO2, standard bicarbonate, base excess and reduced pH were measured in sheep before and at regular intervals after administration of ketamine with and without atropine and acepromazine premedication. A decrease in pH and PaO2 and a rise in PaCO2 was observed 15 minutes after administration of ketamine. Administration of atropine with and without acepromazine had no significant effect on pH, PaCO2 and PaO2. The values for standard bicarbonate, base excess and reduced pH were not significantly affected. This indicates that minor changes observed in pH, PaCO2 after ketamine administration are compensated for by the healthy animal's blood buffer system."}
{"id": "PMID:988", "title": "Molecular nature of beta-galactosidase from different tissues in two strains of the house mouse.", "content": "One inbred mouse strain, C57BL/Kl, has high galactosidase activities in all tissues while another strain, DBA/2/Kl, has low activities determined by the Bgs locus. Beta-Galactosidase from these two strains was partly purified by a five-step procedure: acidification, ammonium sulfate precipitation, gel filtration at two pHs, and isoelectric focusing. No qualitative differences were found between the enzyme preparations from the two strains. They had identical heat inactivation curves, pH optima, molecular weight, and isoelectric points, and the Km values were very similar. It thus seems that this genetic difference in enzyme activity probably cannot be explained by a variation of the galactosidase-specific activity but rather reflects a difference in number of enzyme molecules. Eight different isoenzymes were separated from liver, kidney, and spleen. Each isoenzyme has a different electrophoretic mobility and there is a stepwise increase in molecular weight from 143,000 to 380,000 beginning with the protein having the lowest isoelectric point. A likely interpretation is that the isoenzymes bind a smaller polypeptide in varying numbers in addition to the enzymatic polypeptide per se.", "contents": "Molecular nature of beta-galactosidase from different tissues in two strains of the house mouse. One inbred mouse strain, C57BL/Kl, has high galactosidase activities in all tissues while another strain, DBA/2/Kl, has low activities determined by the Bgs locus. Beta-Galactosidase from these two strains was partly purified by a five-step procedure: acidification, ammonium sulfate precipitation, gel filtration at two pHs, and isoelectric focusing. No qualitative differences were found between the enzyme preparations from the two strains. They had identical heat inactivation curves, pH optima, molecular weight, and isoelectric points, and the Km values were very similar. It thus seems that this genetic difference in enzyme activity probably cannot be explained by a variation of the galactosidase-specific activity but rather reflects a difference in number of enzyme molecules. Eight different isoenzymes were separated from liver, kidney, and spleen. Each isoenzyme has a different electrophoretic mobility and there is a stepwise increase in molecular weight from 143,000 to 380,000 beginning with the protein having the lowest isoelectric point. A likely interpretation is that the isoenzymes bind a smaller polypeptide in varying numbers in addition to the enzymatic polypeptide per se."}
{"id": "PMID:989", "title": "The effects of acute and chronic nicotine hydrogen (+)-tartrate administration and subsequent withdrawal on rat liver tryptophan pyrrolase activity and their comparison with those of morphine, phenobarbitone and ethanol.", "content": "Acute administration of nicotine hydrogen (+)-tartrate enhances the activity of rat liver tryptophan pyrrolase by a hormonal mechanism. Chronic nicotine treatment inhibits, and subsequent withdrawal enhances, the pyrrolase activity. The inhibition during chronic treatment is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. Regeneration of liver NADP+ in vitro and in vivo reverses the inhibition. Chronic nicotine administration increases the liver NADPH concentration. The above effects of nicotine resemble to a remarkable degree those previously shown for morphine, phenobarbitone and ethanol. All effects are compared, and their possible significance in relation to drug dependence is discussed.", "contents": "The effects of acute and chronic nicotine hydrogen (+)-tartrate administration and subsequent withdrawal on rat liver tryptophan pyrrolase activity and their comparison with those of morphine, phenobarbitone and ethanol. Acute administration of nicotine hydrogen (+)-tartrate enhances the activity of rat liver tryptophan pyrrolase by a hormonal mechanism. Chronic nicotine treatment inhibits, and subsequent withdrawal enhances, the pyrrolase activity. The inhibition during chronic treatment is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. Regeneration of liver NADP+ in vitro and in vivo reverses the inhibition. Chronic nicotine administration increases the liver NADPH concentration. The above effects of nicotine resemble to a remarkable degree those previously shown for morphine, phenobarbitone and ethanol. All effects are compared, and their possible significance in relation to drug dependence is discussed."}
{"id": "PMID:990", "title": "Plastid development in primary leaves of Phaseolus vulgaris. Development of plastid adenosine triphosphatase activity during greening.", "content": "The etioplasts of dark-grown bean leaves showed ATPase (adenosine triphosphatase) activity which had a pH optimum of 8.5, was stimulated by dithiothreitol and unaffected by light-triggering. Bean chloroplasts showed a low activity of dark-induced ATPase with a pH optimum of 8.5 and a substantial amount of light-triggered activity with a pH optimum of 8.0. The light-triggered activity depended on dithiothreitol and Mg2+ and was promoted by phenazine methosulphate. Light-triggered ATPase activity was completely inhibited by 20mum-dicyclohexylcarbodi-imide. Etioplasts developed light-triggered ATPase activity in response to 30 min illumination of the etiolated leaves. During the 48 h of light-induced greening of dark-grown leaves there was a 70% increase of the chloroplast ATPase activity found after light-triggering and a 30% fall in the dark-induced activity, both expressed on a per leaf basis. As the larger part of these changes occurred during the first 30 min of illumination, it is concluded that most or all of the chloroplast ATPase was present in the etioplast, a conclusion identical with that of Lockshin et al. (1971) for maize. During 48 h of greening there was a tenfold increase in the amount of thylakoid membrane in the leaf together with an 83% fall in the ATPase activity per m2 of thylakoid membrane, measured after light-triggering.", "contents": "Plastid development in primary leaves of Phaseolus vulgaris. Development of plastid adenosine triphosphatase activity during greening. The etioplasts of dark-grown bean leaves showed ATPase (adenosine triphosphatase) activity which had a pH optimum of 8.5, was stimulated by dithiothreitol and unaffected by light-triggering. Bean chloroplasts showed a low activity of dark-induced ATPase with a pH optimum of 8.5 and a substantial amount of light-triggered activity with a pH optimum of 8.0. The light-triggered activity depended on dithiothreitol and Mg2+ and was promoted by phenazine methosulphate. Light-triggered ATPase activity was completely inhibited by 20mum-dicyclohexylcarbodi-imide. Etioplasts developed light-triggered ATPase activity in response to 30 min illumination of the etiolated leaves. During the 48 h of light-induced greening of dark-grown leaves there was a 70% increase of the chloroplast ATPase activity found after light-triggering and a 30% fall in the dark-induced activity, both expressed on a per leaf basis. As the larger part of these changes occurred during the first 30 min of illumination, it is concluded that most or all of the chloroplast ATPase was present in the etioplast, a conclusion identical with that of Lockshin et al. (1971) for maize. During 48 h of greening there was a tenfold increase in the amount of thylakoid membrane in the leaf together with an 83% fall in the ATPase activity per m2 of thylakoid membrane, measured after light-triggering."}
{"id": "PMID:987", "title": "Influence of some physical factors on survival of Marek's disease vaccine virus.", "content": "Cell-associated Marek's disease (MD) vaccine was suspended at dilutions normally used for vaccination in seven commercially available diluents and in tryptose phosphate broth. The stability of diluted vaccines was determined by assay in cell cultures subjected to 0 to 37 C for 0 to 90 minutes. Optimum holding temperatures for MD vaccine virus survival varied with the specific diluents employed. Some diluents afforded greatest survival when dilution was at 0 C and held at 0 C, while others performed best when dilution was at 25 C followed by cooling and holding at 0 C. Diluents which allowed greatest survival when tested at 37 C also performed well under other temperature regimes. Spectinomycin dihydrochloride pentahydrate and various buffering compounds were added to commercial diluents used for diluting MD vaccine. Additives producing osmolality of 745 mOsm/kg and higher markedly reduced vaccine virus survival. The adverse effects of high osmotic pressure were accentuated by extended holding time, elevated incubation temperature, and physical manipulations including mechanical mixing or expressing through a syringe and needle. Satisfactory MD vaccine virus survival was afforded by a commercial diluent especially formulated to accommodate the pH osmolality changes produced by adding spectinomycin dihydrochloride pentahydrate.", "contents": "Influence of some physical factors on survival of Marek's disease vaccine virus. Cell-associated Marek's disease (MD) vaccine was suspended at dilutions normally used for vaccination in seven commercially available diluents and in tryptose phosphate broth. The stability of diluted vaccines was determined by assay in cell cultures subjected to 0 to 37 C for 0 to 90 minutes. Optimum holding temperatures for MD vaccine virus survival varied with the specific diluents employed. Some diluents afforded greatest survival when dilution was at 0 C and held at 0 C, while others performed best when dilution was at 25 C followed by cooling and holding at 0 C. Diluents which allowed greatest survival when tested at 37 C also performed well under other temperature regimes. Spectinomycin dihydrochloride pentahydrate and various buffering compounds were added to commercial diluents used for diluting MD vaccine. Additives producing osmolality of 745 mOsm/kg and higher markedly reduced vaccine virus survival. The adverse effects of high osmotic pressure were accentuated by extended holding time, elevated incubation temperature, and physical manipulations including mechanical mixing or expressing through a syringe and needle. Satisfactory MD vaccine virus survival was afforded by a commercial diluent especially formulated to accommodate the pH osmolality changes produced by adding spectinomycin dihydrochloride pentahydrate."}
{"id": "PMID:991", "title": "Tricarboxylic acid-cycle and related enzymes in restricted facultative methylotrophs.", "content": "The isolation is described of pure cultures of three non-methane-utilizing methylotrophic bacteria which, together with the previously described Bacillus PM6, have a very limited range of growth substrates; these organisms are designated \"restricted facultative' methylotrophs. Two of these isolates, W6A and W3A1, grow only on glucose out of 50 non-C1 compounds tested, whereas the third isolate S2A1 and Bacillus PM6 grow on betaine, glucose, gluconate, alanine, glutamate, citrate and nutrient agar, but not on any of a further 56 non-C1 compounds. Crude sonic extracts of trimethylamine-grown and glucose-grown W6A and W3A1 isolates, and of trimethylamine-grown C2A1 (an obligate methylotroph) contain (i) no detectable 2-oxogltarate dehydrogenase activity, (ii) very low or zero specific activities of succinate dehydrogenase and succinyl-CoA synthetase and (iii) NAD+-dependent isocitrate dehydrogenase activity. Extracts of trimethylamine-grown PM6 and S2A1 methylotrophs have (i) very low 2-oxoglutarate dehydrogenase specific activities, (ii) comparatively high specific activities of succinate dehydrogenase, malate dehydrogenase and succinyl-CoA synthetase and (iii) NADP+-dependent isocitrate dehydrogenase activity but no NAD+-dependent isocitrate dehydrogenase activity. The activities of most of these enzymes are increased during growth on glucose, alanine, glutamate or citrate, but only very low 2-oxoglutarate dehydrogenase activities are present under all growth conditions. The restricted facultative methylotrophs grow on certain non-C1 compounds in the absence of 2-oxoglutarate dehydrogenase and, in some cases, of other enzymes of the tricarboxylic acid cycle; these lesions cannot therefore be the sole cause of obligate methylotrophy.", "contents": "Tricarboxylic acid-cycle and related enzymes in restricted facultative methylotrophs. The isolation is described of pure cultures of three non-methane-utilizing methylotrophic bacteria which, together with the previously described Bacillus PM6, have a very limited range of growth substrates; these organisms are designated \"restricted facultative' methylotrophs. Two of these isolates, W6A and W3A1, grow only on glucose out of 50 non-C1 compounds tested, whereas the third isolate S2A1 and Bacillus PM6 grow on betaine, glucose, gluconate, alanine, glutamate, citrate and nutrient agar, but not on any of a further 56 non-C1 compounds. Crude sonic extracts of trimethylamine-grown and glucose-grown W6A and W3A1 isolates, and of trimethylamine-grown C2A1 (an obligate methylotroph) contain (i) no detectable 2-oxogltarate dehydrogenase activity, (ii) very low or zero specific activities of succinate dehydrogenase and succinyl-CoA synthetase and (iii) NAD+-dependent isocitrate dehydrogenase activity. Extracts of trimethylamine-grown PM6 and S2A1 methylotrophs have (i) very low 2-oxoglutarate dehydrogenase specific activities, (ii) comparatively high specific activities of succinate dehydrogenase, malate dehydrogenase and succinyl-CoA synthetase and (iii) NADP+-dependent isocitrate dehydrogenase activity but no NAD+-dependent isocitrate dehydrogenase activity. The activities of most of these enzymes are increased during growth on glucose, alanine, glutamate or citrate, but only very low 2-oxoglutarate dehydrogenase activities are present under all growth conditions. The restricted facultative methylotrophs grow on certain non-C1 compounds in the absence of 2-oxoglutarate dehydrogenase and, in some cases, of other enzymes of the tricarboxylic acid cycle; these lesions cannot therefore be the sole cause of obligate methylotrophy."}
{"id": "PMID:992", "title": "Desaturation of stearic acid by liver and adipose tissue from obese-hyperglycaemic mice (ob/ob).", "content": "Stearic acid desaturase activity was assayed in preparations from perigenital adipose tissue and liver from lean and genetically obese female mice (ob/ob). The total activity in the perigenital adipose tissue from obese mice was threefold greater than in the tissue from lean mice, but per g of adipose tissue the activity was twofold greater in tissue from lean mice. In liver, the activity in obese mice was elevated at 8 weeks of age, remained elevated up to 24 weeks and then decreased by half at 48 weeks, but at all ages was higher than that in lean mice. The decrease in desaturase activity of liver from obese mice at 48 weeks corresponded to a change in the fatty acid composition of liver lipids toward that found in lean mice. Whereas in adipose tissue much of the increased enzyme activity may be due to tissue hyperplasia, in liver it is mainly an increased activity per cell.", "contents": "Desaturation of stearic acid by liver and adipose tissue from obese-hyperglycaemic mice (ob/ob). Stearic acid desaturase activity was assayed in preparations from perigenital adipose tissue and liver from lean and genetically obese female mice (ob/ob). The total activity in the perigenital adipose tissue from obese mice was threefold greater than in the tissue from lean mice, but per g of adipose tissue the activity was twofold greater in tissue from lean mice. In liver, the activity in obese mice was elevated at 8 weeks of age, remained elevated up to 24 weeks and then decreased by half at 48 weeks, but at all ages was higher than that in lean mice. The decrease in desaturase activity of liver from obese mice at 48 weeks corresponded to a change in the fatty acid composition of liver lipids toward that found in lean mice. Whereas in adipose tissue much of the increased enzyme activity may be due to tissue hyperplasia, in liver it is mainly an increased activity per cell."}
{"id": "PMID:993", "title": "The stimulation by synaptic transmitters of the incorporation of oleate into the phospholipid of synaptic membranes.", "content": "Noradrenaline stimulated the incorporation of oleate into choline glycerophospholipids of guinea-pig brain synaptic membranes incubated in sodium phosphate buffer. In the presence of 1 mm-NaF, noradrenaline stimulated the incorporation of oleate into the choline glycerophospholipids, phosphatidylinositol, ethanolamine glycerophospholipids, phosphatidylserine and phosphatidic acid of synaptic membranes incubated in 10 mm-Tris-HCl buffer. In Tris-CHl containing 1 mm-NaF, stimulation of incorporation of oleate into choline glycerophospholipids by noradrenaline was enhanced by ATP, CaCl2, MgCl2 and CoA plus dithiothreitol. The optimum concentration of CaCl2 for stimulation by 10 mum-noradrenaline was 10 mum. In the presence of CaCl2, the optimum concentration of ATP-2MgCl2 was in the range 0.1-1 mm. Acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine, histamine and gamma-aminobutyric acid also stimulated the incorporation of oleate into choline glycerophospholipids of synaptic membranes. Sigmoidal dose-response curves were obtained, similar to those obtained previously for stimulation by the same agonists of the hydrolysis of phosphatidylcholine by phospholipase A2 (Gullis & Rowe, 1975a). The initial rate of transfer of oleate from oleoyl-CoA to choline glycerophospholipid was similar to the initial rate of transfer from oleate-albumin, stimulated by noradrenaline. Transfer of oleate from oleoyl-CoA was not appreciably stimulated by noradrenaline, but was stimulated by ATP and MgCl2.", "contents": "The stimulation by synaptic transmitters of the incorporation of oleate into the phospholipid of synaptic membranes. Noradrenaline stimulated the incorporation of oleate into choline glycerophospholipids of guinea-pig brain synaptic membranes incubated in sodium phosphate buffer. In the presence of 1 mm-NaF, noradrenaline stimulated the incorporation of oleate into the choline glycerophospholipids, phosphatidylinositol, ethanolamine glycerophospholipids, phosphatidylserine and phosphatidic acid of synaptic membranes incubated in 10 mm-Tris-HCl buffer. In Tris-CHl containing 1 mm-NaF, stimulation of incorporation of oleate into choline glycerophospholipids by noradrenaline was enhanced by ATP, CaCl2, MgCl2 and CoA plus dithiothreitol. The optimum concentration of CaCl2 for stimulation by 10 mum-noradrenaline was 10 mum. In the presence of CaCl2, the optimum concentration of ATP-2MgCl2 was in the range 0.1-1 mm. Acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine, histamine and gamma-aminobutyric acid also stimulated the incorporation of oleate into choline glycerophospholipids of synaptic membranes. Sigmoidal dose-response curves were obtained, similar to those obtained previously for stimulation by the same agonists of the hydrolysis of phosphatidylcholine by phospholipase A2 (Gullis & Rowe, 1975a). The initial rate of transfer of oleate from oleoyl-CoA to choline glycerophospholipid was similar to the initial rate of transfer from oleate-albumin, stimulated by noradrenaline. Transfer of oleate from oleoyl-CoA was not appreciably stimulated by noradrenaline, but was stimulated by ATP and MgCl2."}
{"id": "PMID:994", "title": "The interaction of magnesium ions with teichoic acid.", "content": "The binding of Mg2+ to the wall teichoic acid of Lactobacillus buchneri N.C.I.B. 8007 was measured by equilibrium dialysis at controlled ionic concentration and pH. In an aqueous solution containing 10mM-NaCl at pH 5.0 one Mg2+ ion was bound for every two phosphate groups of the teichoic acid, with an apparent association constant, Kassoc. = 2.7 x 10(3) M-1. On lowering the pH below the pKa of the phosphate groups the amount of bound Mg2+ decreased concomitantly with decreasing ionization of the phosphate groups. Both the amount of Mg2+ bound to the teichoic acid and the apparent association constants were similar in the presence of 10 mM concentrations of NaCl or KCl but decreased markedly in the presence of 10 mM-CaCl2 because of competition between Ca2+ and Mg2+ for the binding sites. A similar effect was found when the concentration of NaCl was increased from 0 to 50 mM. The results are discussed in relation to the function of teichoic acid in the walls of Gram-positive bacteria.", "contents": "The interaction of magnesium ions with teichoic acid. The binding of Mg2+ to the wall teichoic acid of Lactobacillus buchneri N.C.I.B. 8007 was measured by equilibrium dialysis at controlled ionic concentration and pH. In an aqueous solution containing 10mM-NaCl at pH 5.0 one Mg2+ ion was bound for every two phosphate groups of the teichoic acid, with an apparent association constant, Kassoc. = 2.7 x 10(3) M-1. On lowering the pH below the pKa of the phosphate groups the amount of bound Mg2+ decreased concomitantly with decreasing ionization of the phosphate groups. Both the amount of Mg2+ bound to the teichoic acid and the apparent association constants were similar in the presence of 10 mM concentrations of NaCl or KCl but decreased markedly in the presence of 10 mM-CaCl2 because of competition between Ca2+ and Mg2+ for the binding sites. A similar effect was found when the concentration of NaCl was increased from 0 to 50 mM. The results are discussed in relation to the function of teichoic acid in the walls of Gram-positive bacteria."}
{"id": "PMID:995", "title": "The mechanism of hydrolysis of beta-glycerophosphate by kidney alkaline phosphatase.", "content": "1. To identify the functional groups that are involved in the conversion of beta-glycerophosphate by alkaline phosphatase (EC 3.1.3.1) from pig kidney, the kinetics of alkaline phosphatase were investigated in the pH range 6.6-10.3 at substrate concentrations of 3 muM-30 mM. From the plots of log VH+ against pH and log VH+/KH+m against pH one functional group with pK = 7.0 and two functional groups with pK = 9.1 were identified. These groups are involved in substrate binding. Another group with pK = 8.8 was found, which in its unprotonated form catalyses substrate conversion. 2. GSH inhibits the alkaline phosphatase reversibly and non-competitively by attacking the bound Zn(II). 3. The influence of the H+ concentration on the activation by Mg2+ ions of alkaline pig kidney phosphate was investigated between pH 8.4 and 10.0. The binding of substrate and activating Mg2+ ions occurs independently at all pH values between 8.4 and 10.0. The activation mechanism is not affected by the H+ concentration. The Mg2+ ions are bound by a functional group with a pK of 10.15. 4. A scheme is proposed for the reaction between enzyme, substrate, Mg2+ and H+ and the overall rate equation is derived. 5. The mechanism of substrate binding and splitting by the functional groups of the active centre is discussed on the basis of a model. Mg2+ seems to play a role as an autosteric effector.", "contents": "The mechanism of hydrolysis of beta-glycerophosphate by kidney alkaline phosphatase. 1. To identify the functional groups that are involved in the conversion of beta-glycerophosphate by alkaline phosphatase (EC 3.1.3.1) from pig kidney, the kinetics of alkaline phosphatase were investigated in the pH range 6.6-10.3 at substrate concentrations of 3 muM-30 mM. From the plots of log VH+ against pH and log VH+/KH+m against pH one functional group with pK = 7.0 and two functional groups with pK = 9.1 were identified. These groups are involved in substrate binding. Another group with pK = 8.8 was found, which in its unprotonated form catalyses substrate conversion. 2. GSH inhibits the alkaline phosphatase reversibly and non-competitively by attacking the bound Zn(II). 3. The influence of the H+ concentration on the activation by Mg2+ ions of alkaline pig kidney phosphate was investigated between pH 8.4 and 10.0. The binding of substrate and activating Mg2+ ions occurs independently at all pH values between 8.4 and 10.0. The activation mechanism is not affected by the H+ concentration. The Mg2+ ions are bound by a functional group with a pK of 10.15. 4. A scheme is proposed for the reaction between enzyme, substrate, Mg2+ and H+ and the overall rate equation is derived. 5. The mechanism of substrate binding and splitting by the functional groups of the active centre is discussed on the basis of a model. Mg2+ seems to play a role as an autosteric effector."}
{"id": "PMID:996", "title": "The pH-dependence and group modification of beta-lactamase I.", "content": "The pH-dependence of the kinetic parameters for the hydrolysis of the beta-lactam ring by beta-lactamase I (penicillinase, EC 3.5.2.6) was studied. Benzylpenicillin and ampicillin (6-[D(-)-alpha-aminophenylacetamido]penicillanic acid) were used. Both kcat. and kcat./Km for both substrates gave bell-shaped plots of parameter versus pH. The pH-dependence of kcat./Km for the two substrates gave the same value (8.6) for the higher apparent pK, and so this value may characterize a group on the free enzyme; the lower apparent pK values were about 5(4.85 for benzylpenicillin, 5.4 for ampicillin). For benzylpenicillin both kcat. and kcat./Km depended on pH in exactly the same way. The value of Km for benzylpenicillin was thus independent of pH, suggesting that ionization of the enzyme's catalytically important groups does not affect binding of this substrate. The pH-dependence of kcat. for ampicillin differed, however, presumably because of the polar group in the side chain. The hypothesis that the pK5 group is a carboxyl group was tested. Three reagents that normally react preferentially with carboxyl groups inactivated the enzyme: the reagents were Woodward's reagent K, a water-soluble carbodi-imide, and triethyloxonium fluoroborate. These findings tend to support the idea that a carboxylate group plays a part in the action of beta-lactamase I.", "contents": "The pH-dependence and group modification of beta-lactamase I. The pH-dependence of the kinetic parameters for the hydrolysis of the beta-lactam ring by beta-lactamase I (penicillinase, EC 3.5.2.6) was studied. Benzylpenicillin and ampicillin (6-[D(-)-alpha-aminophenylacetamido]penicillanic acid) were used. Both kcat. and kcat./Km for both substrates gave bell-shaped plots of parameter versus pH. The pH-dependence of kcat./Km for the two substrates gave the same value (8.6) for the higher apparent pK, and so this value may characterize a group on the free enzyme; the lower apparent pK values were about 5(4.85 for benzylpenicillin, 5.4 for ampicillin). For benzylpenicillin both kcat. and kcat./Km depended on pH in exactly the same way. The value of Km for benzylpenicillin was thus independent of pH, suggesting that ionization of the enzyme's catalytically important groups does not affect binding of this substrate. The pH-dependence of kcat. for ampicillin differed, however, presumably because of the polar group in the side chain. The hypothesis that the pK5 group is a carboxyl group was tested. Three reagents that normally react preferentially with carboxyl groups inactivated the enzyme: the reagents were Woodward's reagent K, a water-soluble carbodi-imide, and triethyloxonium fluoroborate. These findings tend to support the idea that a carboxylate group plays a part in the action of beta-lactamase I."}
{"id": "PMID:997", "title": "Oxidase-peroxidase enzymes of Datura innoxia. Oxidation of formylphenylacetic acid ethyl ester.", "content": "An enzyme system from Datura innoxia roots oxidizing formylphenylacetic acid ethyl ester was purified 38-fold by conventional methods such as (NH4)2SO4 fractionation, negative adsorption on alumina Cy gel and chromatography on DEAE-cellulose. The purified enzyme was shown to catalyse the stoicheiometric oxidation of formylphenylacetic acid ethyl ester to benzoylformic acid ethyl ester and formic acid, utilizing molecular O2. Substrate analogues such as phenylacetaldehyde and phenylpyruvate were oxidized at a very low rate, and formylphenylacetonitrile was an inhilating agents, cyanide, thiol compounds and ascorbic acid. This enzyme was identical with an oxidase-peroxidase isoenzyme. Another oxidase-peroxidase isoenzyme which separated on DEAE-chromatography also showed formylphenylacetic acid ethyl ester oxidase activity, albeit to a lesser extent. The properties of the two isoenzymes of the oxidase were compared and shown to differ in their oxidation and peroxidation properties. The oxidation of formylphenylacetic acid ethyl ester was also catalysed by horseradish peroxidase. The Datura isoenzymes exhibited typical haemoprotein spectra. The oxidation of formylphenylacetic acid ethyl ester was different from other peroxidase-catalysed reactions in not being activated by either Mn2+ or monophenols. The oxidation was inhibited by several mono- and poly-phenols and by catalase. A reaction mechanism for the oxidation is proposed.", "contents": "Oxidase-peroxidase enzymes of Datura innoxia. Oxidation of formylphenylacetic acid ethyl ester. An enzyme system from Datura innoxia roots oxidizing formylphenylacetic acid ethyl ester was purified 38-fold by conventional methods such as (NH4)2SO4 fractionation, negative adsorption on alumina Cy gel and chromatography on DEAE-cellulose. The purified enzyme was shown to catalyse the stoicheiometric oxidation of formylphenylacetic acid ethyl ester to benzoylformic acid ethyl ester and formic acid, utilizing molecular O2. Substrate analogues such as phenylacetaldehyde and phenylpyruvate were oxidized at a very low rate, and formylphenylacetonitrile was an inhilating agents, cyanide, thiol compounds and ascorbic acid. This enzyme was identical with an oxidase-peroxidase isoenzyme. Another oxidase-peroxidase isoenzyme which separated on DEAE-chromatography also showed formylphenylacetic acid ethyl ester oxidase activity, albeit to a lesser extent. The properties of the two isoenzymes of the oxidase were compared and shown to differ in their oxidation and peroxidation properties. The oxidation of formylphenylacetic acid ethyl ester was also catalysed by horseradish peroxidase. The Datura isoenzymes exhibited typical haemoprotein spectra. The oxidation of formylphenylacetic acid ethyl ester was different from other peroxidase-catalysed reactions in not being activated by either Mn2+ or monophenols. The oxidation was inhibited by several mono- and poly-phenols and by catalase. A reaction mechanism for the oxidation is proposed."}
{"id": "PMID:998", "title": "Purification of 2-oxoaldehyde dehydrogenase and its dependence on unusual amines.", "content": "1. 2-Oxoaldehyde dehydrogenase was purified from sheep liver and gave one band on polyacrylamide-gel electrophoresis. 2. The enzyme was completely dependent for its activity on the presence of Tris or one of a number of related amines, all of general structure: (See article). When more than one R group was hydrogen no enzyme activity was observed. 3. Only one of these amines is known to exist in living tissues and large concentrations of all amines were required for maximum activity. L-2-Aminopropan-1-ol was the most effective amine on the basis of substrate Km and Vmax. values and the amine Km values. 4. The enzyme was activated by phosphate which lowered the Km values for methylglyoxal, amine and NAD+. 5. The pH optimum of the enzyme was 9.3 and there was no activity at pH values below 7.8. A search for activators that might produce activity at pH 7.4 proved unsuccessful. 6. The enzyme was inhibited by rather large concentrations of barbiturates (6-46 mM) and nitro-alcohol analogues of the activating amines (66-139 mM).", "contents": "Purification of 2-oxoaldehyde dehydrogenase and its dependence on unusual amines. 1. 2-Oxoaldehyde dehydrogenase was purified from sheep liver and gave one band on polyacrylamide-gel electrophoresis. 2. The enzyme was completely dependent for its activity on the presence of Tris or one of a number of related amines, all of general structure: (See article). When more than one R group was hydrogen no enzyme activity was observed. 3. Only one of these amines is known to exist in living tissues and large concentrations of all amines were required for maximum activity. L-2-Aminopropan-1-ol was the most effective amine on the basis of substrate Km and Vmax. values and the amine Km values. 4. The enzyme was activated by phosphate which lowered the Km values for methylglyoxal, amine and NAD+. 5. The pH optimum of the enzyme was 9.3 and there was no activity at pH values below 7.8. A search for activators that might produce activity at pH 7.4 proved unsuccessful. 6. The enzyme was inhibited by rather large concentrations of barbiturates (6-46 mM) and nitro-alcohol analogues of the activating amines (66-139 mM)."}
{"id": "PMID:999", "title": "Determination of polyadenylate-rich ribonucleic acid in the nucleus and in the cytoplasm of plasmacytoma cells.", "content": "A number of parameters affecting the adsorption of rRNA and poly(A)-containing RNA to Millipore filters were investigated separately. Binding of both types of RNA to the filter was dependent on the concentration of RNA, pH and Mg2+ concentration of the reaction mixture. Both types of RNA bound to the filter optimally at slightly acid pH values. The binding of poly(A)-containing RNA to the filter exhibited a broad pH-dependence compared with that of rRNA. The ratio of poly(A)-rich RNA/rRNA retained by the filter was maximal between pH7 and 8. The presence of 1 mM-EDTA or a high concentration of NaCl (over 0.5M) decreased the affinity of RNA for the filter. The amount of poly(A)-containing RNA in the nucleus and in the cytoplasm of a plasmacytoma cell line (MPC-11) labelled with [32P]Pi was determined by the Millipore-filter technique under conditions that minimized contamination by rRNA. These data were compared with the estimations made by oligo(dT)-cellulose chromatography. The results obtained by these two methods were in good agreement for RNA labelled for short periods (up to 2h). In long labelling and pulse-chase experiments, however, contamination of the filter by rRNA of increasing specific radioactivity in the cytoplasm gave an erroneous value for poly(A)-containing RNA by the Millipore-filter technique. Determinations made on the nuclear fraction by these two methods did not show significant variation in short- and long-term labelling experiments.", "contents": "Determination of polyadenylate-rich ribonucleic acid in the nucleus and in the cytoplasm of plasmacytoma cells. A number of parameters affecting the adsorption of rRNA and poly(A)-containing RNA to Millipore filters were investigated separately. Binding of both types of RNA to the filter was dependent on the concentration of RNA, pH and Mg2+ concentration of the reaction mixture. Both types of RNA bound to the filter optimally at slightly acid pH values. The binding of poly(A)-containing RNA to the filter exhibited a broad pH-dependence compared with that of rRNA. The ratio of poly(A)-rich RNA/rRNA retained by the filter was maximal between pH7 and 8. The presence of 1 mM-EDTA or a high concentration of NaCl (over 0.5M) decreased the affinity of RNA for the filter. The amount of poly(A)-containing RNA in the nucleus and in the cytoplasm of a plasmacytoma cell line (MPC-11) labelled with [32P]Pi was determined by the Millipore-filter technique under conditions that minimized contamination by rRNA. These data were compared with the estimations made by oligo(dT)-cellulose chromatography. The results obtained by these two methods were in good agreement for RNA labelled for short periods (up to 2h). In long labelling and pulse-chase experiments, however, contamination of the filter by rRNA of increasing specific radioactivity in the cytoplasm gave an erroneous value for poly(A)-containing RNA by the Millipore-filter technique. Determinations made on the nuclear fraction by these two methods did not show significant variation in short- and long-term labelling experiments."}
{"id": "PMID:1000", "title": "The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. The tryptic peptides.", "content": "The NADP-specific glutamate dehydrogenase of Neurospora crassa was digested with trypsin, and peptides accounting for 441 out of the 452 residues of the polypeptide chain were isolated and substantially sequenced. Additional experimental detail has been deposited as Supplementary Publication SUP 50052 (11 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem J. (1975) 145, 5.", "contents": "The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. The tryptic peptides. The NADP-specific glutamate dehydrogenase of Neurospora crassa was digested with trypsin, and peptides accounting for 441 out of the 452 residues of the polypeptide chain were isolated and substantially sequenced. Additional experimental detail has been deposited as Supplementary Publication SUP 50052 (11 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem J. (1975) 145, 5."}
{"id": "PMID:1001", "title": "The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. Peptides from digestion with a staphylococcal proteinase.", "content": "The extracellular proteinase of Staphylococcus aureus strain V8 was used to digest the NADP-specific glutamate dehydrogenase of Neurospora crassa. Of 35 non-overlapping peptides expected from the glutamate content of the polypeptide chain, 29 were isolated and substantially sequenced. The sequences obtained were valuable in providing overlaps for the alignment of about two-thirds of the sequences found in tryptic peptides [Wootton, J. C., Taylor, J, G., Jackson, A. A., Chambers, G. K. & Fincham, J. R. S. (1975) Biochem. J. 149, 739-748]. The blocked N-terminal peptide of the protein was isolated. This peptide was sequenced by mass spectrometry, and found to have N-terminal N-acetylserine by Howard R. Morris and Anne Dell, whose results are presented as an Appendix to the main paper. The staphylococcal proteinase showed very high specificity for glutamyl bonds in the NH4HCO3 buffer used. Partial splits of two aspartyl bonds, both Asp-Ile, were probably attributable to the proteinase. No cleavage of glutaminyl or S-carboxymethylcysteinyl bonds was found. Additional experimental detail has been deposited as Supplementary Publication SUP 50053 (5 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K, from whom copies may be obtained under the terms given in Biochem. J. (1975) 1458 5.", "contents": "The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. Peptides from digestion with a staphylococcal proteinase. The extracellular proteinase of Staphylococcus aureus strain V8 was used to digest the NADP-specific glutamate dehydrogenase of Neurospora crassa. Of 35 non-overlapping peptides expected from the glutamate content of the polypeptide chain, 29 were isolated and substantially sequenced. The sequences obtained were valuable in providing overlaps for the alignment of about two-thirds of the sequences found in tryptic peptides [Wootton, J. C., Taylor, J, G., Jackson, A. A., Chambers, G. K. & Fincham, J. R. S. (1975) Biochem. J. 149, 739-748]. The blocked N-terminal peptide of the protein was isolated. This peptide was sequenced by mass spectrometry, and found to have N-terminal N-acetylserine by Howard R. Morris and Anne Dell, whose results are presented as an Appendix to the main paper. The staphylococcal proteinase showed very high specificity for glutamyl bonds in the NH4HCO3 buffer used. Partial splits of two aspartyl bonds, both Asp-Ile, were probably attributable to the proteinase. No cleavage of glutaminyl or S-carboxymethylcysteinyl bonds was found. Additional experimental detail has been deposited as Supplementary Publication SUP 50053 (5 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K, from whom copies may be obtained under the terms given in Biochem. J. (1975) 1458 5."}
{"id": "PMID:1002", "title": "The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. Peptic and chymotryptic peptides and the complete sequence.", "content": "Peptic and chymotryptic peptides were isolated form the NADP-specific glutamate dehydrogenase of Neurospora crassa and substantially sequenced. Out of 452 residues in the polypeptide chain, 265 were recovered in the peptic and 427 in the chymotryptic peptides. Together with the tryptic peptides [Wootton, J. C., Taylor, J. G., Jackson, A. A., Chambers, G. K. & Fincham, J. R. S. (1975) Biochem. J. 149, 749-755], these establish the complete sequence of the chain, including the acid and amide assignments, except for seven places where overlaps are inadequate. These remaining alignments are deduced from information on the CNBr fragments obtained in another laboratory [Blumenthal, K. M., Moon, K. & Smith, E. L. (1975), J. Biol. Chem. 250, 3644-3654]. Further information has been deposited as Supplementary Publication SUP 50054 (17 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem. J. (1975) 145, 5.", "contents": "The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. Peptic and chymotryptic peptides and the complete sequence. Peptic and chymotryptic peptides were isolated form the NADP-specific glutamate dehydrogenase of Neurospora crassa and substantially sequenced. Out of 452 residues in the polypeptide chain, 265 were recovered in the peptic and 427 in the chymotryptic peptides. Together with the tryptic peptides [Wootton, J. C., Taylor, J. G., Jackson, A. A., Chambers, G. K. & Fincham, J. R. S. (1975) Biochem. J. 149, 749-755], these establish the complete sequence of the chain, including the acid and amide assignments, except for seven places where overlaps are inadequate. These remaining alignments are deduced from information on the CNBr fragments obtained in another laboratory [Blumenthal, K. M., Moon, K. & Smith, E. L. (1975), J. Biol. Chem. 250, 3644-3654]. Further information has been deposited as Supplementary Publication SUP 50054 (17 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem. J. (1975) 145, 5."}
{"id": "PMID:1003", "title": "Activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenases, glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in nervous tissues from vertebrates and invertebrates.", "content": "1. The activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenases were measured in nervous tissue from different animals in an attempt to provide more information about the citric acid cycle in this tissue. In higher animals the activities of citrate synthase are greater than the sum of activities of the isocitrate dehydrogenases, whereas they are similar in nervous tissues from the lower animals. This suggests that in higher animals the isocitrate dehydrogenase reaction is far-removed from equilibrium. If it is assumed that isocitrate dehydrogenase activities provide an indication of the maximum flux through the citric acid cycle, the maximum glycolytic capacity in nervous tissue is considerably greater than that of the cycle. This suggest that glycolysis can provide energy in excess of the aerobic capacity of the tissue. 2. The activities of glutamate dehydrogenase are high in most nervous tissues and the activities of aspartate aminotransferase are high in all nervous tissue investigated. However, the activities of alanine aminotransferase are low in all tissues except the ganglia of the waterbug and cockroach. In these insect tissues, anaerobic glycolysis may result in the formation of alanine rather than lactate.", "contents": "Activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenases, glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in nervous tissues from vertebrates and invertebrates. 1. The activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenases were measured in nervous tissue from different animals in an attempt to provide more information about the citric acid cycle in this tissue. In higher animals the activities of citrate synthase are greater than the sum of activities of the isocitrate dehydrogenases, whereas they are similar in nervous tissues from the lower animals. This suggests that in higher animals the isocitrate dehydrogenase reaction is far-removed from equilibrium. If it is assumed that isocitrate dehydrogenase activities provide an indication of the maximum flux through the citric acid cycle, the maximum glycolytic capacity in nervous tissue is considerably greater than that of the cycle. This suggest that glycolysis can provide energy in excess of the aerobic capacity of the tissue. 2. The activities of glutamate dehydrogenase are high in most nervous tissues and the activities of aspartate aminotransferase are high in all nervous tissue investigated. However, the activities of alanine aminotransferase are low in all tissues except the ganglia of the waterbug and cockroach. In these insect tissues, anaerobic glycolysis may result in the formation of alanine rather than lactate."}
{"id": "PMID:1004", "title": "Properties of 5-aminolaevulinate synthetase and its relationship to microsomal mixed-function oxidation in the southern armyworm (Spodoptera eridania).", "content": "1. Activity of 5-aminolaevulinate synthetase was measured in the midgut and other tissues of the last larval instar of the southern armyworm (Spodoptera eridania Cramer, formerly Prodenia eridania Cramer). 2. Optimum conditions for measuring the activity were established with respect to all variables involved and considerable differences from those reported for mammalian enzyme preparations were found. 3. Maximum activity (20 nmol/h per mg of protein) occurs 18-24 h after the fifth moult and thereafter decreases to trace amounts as the larvae age and approach pupation. 4. Synthetase activity was rapidly induced by oral administration (in the diet) of pentamethylbenzene, phenobarbital, diethyl 1,4-dihydro-2,4,6-trimethylpyridine-3, 5-dicarboxylate, and 2-allyl-2-isopropylacetamide. 5. Puromycin inhibited the induction of synthetase by pentamethylbenzene. 6. Induction of 5-aminolaevulinate synthetase correlated well with the induction of microsomal N-demethylation of p-chloro-N-methylaniline, except for phenobarbital, which induced the microsomal oxidase relatively more than the synthetase.", "contents": "Properties of 5-aminolaevulinate synthetase and its relationship to microsomal mixed-function oxidation in the southern armyworm (Spodoptera eridania). 1. Activity of 5-aminolaevulinate synthetase was measured in the midgut and other tissues of the last larval instar of the southern armyworm (Spodoptera eridania Cramer, formerly Prodenia eridania Cramer). 2. Optimum conditions for measuring the activity were established with respect to all variables involved and considerable differences from those reported for mammalian enzyme preparations were found. 3. Maximum activity (20 nmol/h per mg of protein) occurs 18-24 h after the fifth moult and thereafter decreases to trace amounts as the larvae age and approach pupation. 4. Synthetase activity was rapidly induced by oral administration (in the diet) of pentamethylbenzene, phenobarbital, diethyl 1,4-dihydro-2,4,6-trimethylpyridine-3, 5-dicarboxylate, and 2-allyl-2-isopropylacetamide. 5. Puromycin inhibited the induction of synthetase by pentamethylbenzene. 6. Induction of 5-aminolaevulinate synthetase correlated well with the induction of microsomal N-demethylation of p-chloro-N-methylaniline, except for phenobarbital, which induced the microsomal oxidase relatively more than the synthetase."}
{"id": "PMID:1040", "title": "Nitrosation of phenacetin. Formation of N-nitroso-2-nitro-4-ethoxyacetanilide as an unstable product of the nitrosation in dilute aqueous-acidic solution.", "content": "Reaction of phenacetin with N2O4 in glacial acetic acid at 10(0) C gives N-nitroso-2-nitro-4-ethoxyacetanilide. This N-nitrosoacylarylamine is stable at low temperatures (--30 degress C) but unstable at ambient temperature. No intact N-nitroso-2-nitro-4-ethoxyacetanilide can be detected when phenacetin is nitrosated under conditions simulating those in the stomach (37 degrees C, pH 1). Instead, 2-nitro-4-ethoxybenzenediazonium chloride is the main reaction product found. Under the conditions applied, the N-nitrosoacylarylamine rapidly rearranges by 1,3-migration of the acetyl group. The resulting diazoester dissociates into the corresponding diazonium salt. Trapping of the diazonium ion with 1-naphthol as an azo dye provides a useful means to identify the parent N-nitroso compound and to measure colorimetrically its rate of formation. The yields obtained in dilute aqueous nitrosation mixtures are lower than expected; the reasons for this finding are discussed. Preliminary results of animal experiments show that the N-nitroso compound is a directly acting carcinogen.", "contents": "Nitrosation of phenacetin. Formation of N-nitroso-2-nitro-4-ethoxyacetanilide as an unstable product of the nitrosation in dilute aqueous-acidic solution. Reaction of phenacetin with N2O4 in glacial acetic acid at 10(0) C gives N-nitroso-2-nitro-4-ethoxyacetanilide. This N-nitrosoacylarylamine is stable at low temperatures (--30 degress C) but unstable at ambient temperature. No intact N-nitroso-2-nitro-4-ethoxyacetanilide can be detected when phenacetin is nitrosated under conditions simulating those in the stomach (37 degrees C, pH 1). Instead, 2-nitro-4-ethoxybenzenediazonium chloride is the main reaction product found. Under the conditions applied, the N-nitrosoacylarylamine rapidly rearranges by 1,3-migration of the acetyl group. The resulting diazoester dissociates into the corresponding diazonium salt. Trapping of the diazonium ion with 1-naphthol as an azo dye provides a useful means to identify the parent N-nitroso compound and to measure colorimetrically its rate of formation. The yields obtained in dilute aqueous nitrosation mixtures are lower than expected; the reasons for this finding are discussed. Preliminary results of animal experiments show that the N-nitroso compound is a directly acting carcinogen."}
{"id": "PMID:1041", "title": "[Thermographic and histologic studies of the antiinflammatory effect of benorilate by means of the cotton pellet test in the rat (author's transl)].", "content": "1. The effect of (4-acetamido-phenyl)-2-acetoxy-benzoate (benorilate, Benortan) on the inflammatory process was studied thermographically and histologically in cotton-pellet tests on rats. 2. Following implantation of the cotton-pellet, thermography shows a clear inhibition of the local inflammation due to treatment with benorilate. 3. Histological examination shows a corresponding influence of benorilate upon the proliferative phase of the inflammation. 4. The success of antiphlogistic therapy is in correlation with the time of medication.", "contents": "[Thermographic and histologic studies of the antiinflammatory effect of benorilate by means of the cotton pellet test in the rat (author's transl)]. 1. The effect of (4-acetamido-phenyl)-2-acetoxy-benzoate (benorilate, Benortan) on the inflammatory process was studied thermographically and histologically in cotton-pellet tests on rats. 2. Following implantation of the cotton-pellet, thermography shows a clear inhibition of the local inflammation due to treatment with benorilate. 3. Histological examination shows a corresponding influence of benorilate upon the proliferative phase of the inflammation. 4. The success of antiphlogistic therapy is in correlation with the time of medication."}
{"id": "PMID:1042", "title": "Acidic antiinflammatory agents--correlations of some physical, pharmacological and clinical data.", "content": "Fifteen acidic antiinflammatory agents, for which some clinical data have previously been published, have been examined for their potency in the carrageenan-induced rat foot edema test, and for their acidity (pKa) and partition coefficients. Published serum half-life data and daily clinical (anti-arthritic) dose have been tabulated for these drugs and correlations between these various parameters are discussed. The rat foot edema carrageenan test has proved to be a fairly reliable predictor of clinical dose for most acidic antiinflammatory agents of moderate serum half-life.", "contents": "Acidic antiinflammatory agents--correlations of some physical, pharmacological and clinical data. Fifteen acidic antiinflammatory agents, for which some clinical data have previously been published, have been examined for their potency in the carrageenan-induced rat foot edema test, and for their acidity (pKa) and partition coefficients. Published serum half-life data and daily clinical (anti-arthritic) dose have been tabulated for these drugs and correlations between these various parameters are discussed. The rat foot edema carrageenan test has proved to be a fairly reliable predictor of clinical dose for most acidic antiinflammatory agents of moderate serum half-life."}
{"id": "PMID:1043", "title": "[Clinical trial of a novel benzodiazepine derivative in a double-blind study using the Wittenborn psychiatric rating scale (author's transl)].", "content": "From testing a new benzodiazepine derivative, 8-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one (Bu 1014), as measured against a placebo in a double-blind trial, the following conclusions can be drawn. The test was carried out over two periods of a fortnight each with a change-over between the two periods. 1. The change-over method has proven suitable to reveal side effects of the substance which last for at least two weeks. Owing to the substance's sequelae, however, statistical analysis of the second treatment period's information is not possible with this experimental design. 2. The statistical methods used proved more effective than the usual methods as they allow clearer statements to be made on the efficacy of the substance. 3. Within the first period of 14 days both the group receiving the placebo and the drug treated group showed a decrease in the intensity of anxiety. 4. The sequelae of Bu 1014 can be described as an increase in restiveness and anxiety in those patients who received the placebo in the second treatment period.", "contents": "[Clinical trial of a novel benzodiazepine derivative in a double-blind study using the Wittenborn psychiatric rating scale (author's transl)]. From testing a new benzodiazepine derivative, 8-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one (Bu 1014), as measured against a placebo in a double-blind trial, the following conclusions can be drawn. The test was carried out over two periods of a fortnight each with a change-over between the two periods. 1. The change-over method has proven suitable to reveal side effects of the substance which last for at least two weeks. Owing to the substance's sequelae, however, statistical analysis of the second treatment period's information is not possible with this experimental design. 2. The statistical methods used proved more effective than the usual methods as they allow clearer statements to be made on the efficacy of the substance. 3. Within the first period of 14 days both the group receiving the placebo and the drug treated group showed a decrease in the intensity of anxiety. 4. The sequelae of Bu 1014 can be described as an increase in restiveness and anxiety in those patients who received the placebo in the second treatment period."}
{"id": "PMID:1048", "title": "Flavoxate and 3-methylflavone-8-carboxylic acid. Assay methods in blood and urine, plasma-red cells repartition and stability.", "content": "The following assay methods for pharmacokinetic studies on flavoxate (F) and on its main metabolite, i.e. 3-methylflavone-8-carboxylic acid (A), are described. 1. Spectrophotometry for the assay of F and of A in plasma, 2. TLC-Spectrodensitometry and GLC for the assay of A in urine after acid hydrolysis, 3. TLC-Spectrodensitometry for determining the F : A ratio in plasma or in urine. It was found that F hydrolyzes into A. This process depends on the pH and on the medium. In water, at pH 5.0, F is stable, while in phosphate buffer at pH 7.4 the semi-hydrolysis time is 60 min. In a solution with bovine serum albumin, in rat, rabbit, dog or human plasma the semi-hydrolysis times are between 5 and 60 min. Finally the plasma-red cells repartitions of F and of A were studied in vitro in rat, rabbit, dog and human blood and found between 0.8 and 2.0 for F and between 2.1 and 4.6 for A.", "contents": "Flavoxate and 3-methylflavone-8-carboxylic acid. Assay methods in blood and urine, plasma-red cells repartition and stability. The following assay methods for pharmacokinetic studies on flavoxate (F) and on its main metabolite, i.e. 3-methylflavone-8-carboxylic acid (A), are described. 1. Spectrophotometry for the assay of F and of A in plasma, 2. TLC-Spectrodensitometry and GLC for the assay of A in urine after acid hydrolysis, 3. TLC-Spectrodensitometry for determining the F : A ratio in plasma or in urine. It was found that F hydrolyzes into A. This process depends on the pH and on the medium. In water, at pH 5.0, F is stable, while in phosphate buffer at pH 7.4 the semi-hydrolysis time is 60 min. In a solution with bovine serum albumin, in rat, rabbit, dog or human plasma the semi-hydrolysis times are between 5 and 60 min. Finally the plasma-red cells repartitions of F and of A were studied in vitro in rat, rabbit, dog and human blood and found between 0.8 and 2.0 for F and between 2.1 and 4.6 for A."}
{"id": "PMID:1049", "title": "[On the pharmacology of 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335), a histamine and serotonin antagonist (author's transl)].", "content": "The substance 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335) was examined for its antagonistic effects against histamine and serotonin, for its atropine-like properties as well as for a series of other qualities in comparison with cyproheptadine and pimethixene. The anti-histamine and anti-serotonin activities of compound WA 335 on the smooth muscle and the capillary do not only exceed that of cyproheptadine but also that of pimethixene. WA 335 shows an extremely strong binding to histamine and serotonin receptors. In the dose range in which it causes already an antamine effect, its oral absorption is very good. The anti-anaphylactic effect is much stronger than that of cyproheptadine. Like pimethixene and cyproheptadine, WA 335 has no distinct antagonistic qualities against bradykinin. The anticholinergic effects of WA 335 are dependent on the test object. In examinations on the bronchus of the guinea pig and the pupil of the mouse, the atropine-like efficiency corresponds to that of cyproheptadine; it is stronger on the stimulated vagus of the cat and less efficient than cyproheptadine on the stomach of the rat. WA 335 has distinct central atropine-like properties. It possesses a strong surface anesthetic activity. The effects of WA 335 on circulation are dependent on species. In contrast to pimethixene, compound WA 335 like cyproheptadine potentiates the effects of norepinephrine in cats. The reduction of the carotid sinus reflex in the cat is more distinct after WA 335 than after pimethixene and corresponds to that produced by cyproheptadine. Higher doses of WA 335 than are necessary to demonstrate antaminic effects are needed to provoke central nervous effects. WA 335 shows no analgesic potency in mice. The influence on body temperature in the rat is similar to that of cyproheptadine. WA 335 is equally efficient as pimethixene with regard to the inhibition of spontaneous motility and prolongation of barbiturate sleep in mice, and shows the same anti-emetic activity as does chlorpromazine in dogs. In contrast to chlorpromazine the behaviour of dogs and cats is distinctly altered already by doses of WA 335 which cause a slight sedation.", "contents": "[On the pharmacology of 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335), a histamine and serotonin antagonist (author's transl)]. The substance 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335) was examined for its antagonistic effects against histamine and serotonin, for its atropine-like properties as well as for a series of other qualities in comparison with cyproheptadine and pimethixene. The anti-histamine and anti-serotonin activities of compound WA 335 on the smooth muscle and the capillary do not only exceed that of cyproheptadine but also that of pimethixene. WA 335 shows an extremely strong binding to histamine and serotonin receptors. In the dose range in which it causes already an antamine effect, its oral absorption is very good. The anti-anaphylactic effect is much stronger than that of cyproheptadine. Like pimethixene and cyproheptadine, WA 335 has no distinct antagonistic qualities against bradykinin. The anticholinergic effects of WA 335 are dependent on the test object. In examinations on the bronchus of the guinea pig and the pupil of the mouse, the atropine-like efficiency corresponds to that of cyproheptadine; it is stronger on the stimulated vagus of the cat and less efficient than cyproheptadine on the stomach of the rat. WA 335 has distinct central atropine-like properties. It possesses a strong surface anesthetic activity. The effects of WA 335 on circulation are dependent on species. In contrast to pimethixene, compound WA 335 like cyproheptadine potentiates the effects of norepinephrine in cats. The reduction of the carotid sinus reflex in the cat is more distinct after WA 335 than after pimethixene and corresponds to that produced by cyproheptadine. Higher doses of WA 335 than are necessary to demonstrate antaminic effects are needed to provoke central nervous effects. WA 335 shows no analgesic potency in mice. The influence on body temperature in the rat is similar to that of cyproheptadine. WA 335 is equally efficient as pimethixene with regard to the inhibition of spontaneous motility and prolongation of barbiturate sleep in mice, and shows the same anti-emetic activity as does chlorpromazine in dogs. In contrast to chlorpromazine the behaviour of dogs and cats is distinctly altered already by doses of WA 335 which cause a slight sedation."}
{"id": "PMID:1050", "title": "[Central action of WA-335-BS, a substance with peripheral antiserotonin and antihistaminic activity].", "content": "In rats and mice the serotonin and histamine antagonistic drug 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335-BS) caused stronger central sedative effects than did cyproheptadine. WA 335-BS also displayed stronger activity against reserpine- and central tremorine-induced effects than did cyproheptadine and it slightly enhanced d-amphetamine-induced effects: therefore it may have antidepressant properties. WA 335-BS proved to be very effective against isolation-induced aggression in male mice. The comparatively small anxiolytic effects may have been caused in part by the central antiserotonin properties. Like cyproheptadine, WA 335-BS increased food consumption in cats. In EEG-experiments in the conscious rabbit the serotonin-antagonistic drugs WA 335-BS and cyproheptadine exerted stronger depressant activity on the arousal reactions than did the neuroleptic chlorpromazine. The results of our animal studies suggest WA 335-BS to be an antidepressant with sedative properties.", "contents": "[Central action of WA-335-BS, a substance with peripheral antiserotonin and antihistaminic activity]. In rats and mice the serotonin and histamine antagonistic drug 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335-BS) caused stronger central sedative effects than did cyproheptadine. WA 335-BS also displayed stronger activity against reserpine- and central tremorine-induced effects than did cyproheptadine and it slightly enhanced d-amphetamine-induced effects: therefore it may have antidepressant properties. WA 335-BS proved to be very effective against isolation-induced aggression in male mice. The comparatively small anxiolytic effects may have been caused in part by the central antiserotonin properties. Like cyproheptadine, WA 335-BS increased food consumption in cats. In EEG-experiments in the conscious rabbit the serotonin-antagonistic drugs WA 335-BS and cyproheptadine exerted stronger depressant activity on the arousal reactions than did the neuroleptic chlorpromazine. The results of our animal studies suggest WA 335-BS to be an antidepressant with sedative properties."}
{"id": "PMID:1051", "title": "The distribution and elimination of radioactivity in the rat after administration of 14C-4-acetamidophenyl-2-acetoxybenzoate (benorylate).", "content": "Following oral administration of 4-acetamido-phenyl-2-acetoxybenzoate (carboxyl-14C) (benorylate) to rats, no gross differences were detected 7.5 h after administration with respect to the distribution of 14C in various tissues, including the upper sections of the small intestine. A high concentration of 14C was found in the lower sections of the intestine 4 h after administration. The 14C in the intestine was present as unchanged benorylate, as detected by thin-layer chromatography, suggesting that benorylate absorption was slow. Intravenous injection of 14C-benorylate to rats showed that the drug had a relatively high elimination rate from the blood with a half-life of 1.9 h. In blood benorylate must be rapidly hydrolysed enzymatically since no 14C-metabolites, other than salicylic acid, could be detected.", "contents": "The distribution and elimination of radioactivity in the rat after administration of 14C-4-acetamidophenyl-2-acetoxybenzoate (benorylate). Following oral administration of 4-acetamido-phenyl-2-acetoxybenzoate (carboxyl-14C) (benorylate) to rats, no gross differences were detected 7.5 h after administration with respect to the distribution of 14C in various tissues, including the upper sections of the small intestine. A high concentration of 14C was found in the lower sections of the intestine 4 h after administration. The 14C in the intestine was present as unchanged benorylate, as detected by thin-layer chromatography, suggesting that benorylate absorption was slow. Intravenous injection of 14C-benorylate to rats showed that the drug had a relatively high elimination rate from the blood with a half-life of 1.9 h. In blood benorylate must be rapidly hydrolysed enzymatically since no 14C-metabolites, other than salicylic acid, could be detected."}
{"id": "PMID:1052", "title": "Comparative studies of parasympatholytic drugs on stomach (double blind test) and analysis of relation between gastric form and tonus.", "content": "Effects of 3 kinds of parasympatholytic drugs (timepidiumbromide, hyoscine-N-butylbromide and prifinium-bromide) and placebo (physiological saline solution) on the gastrointestinal tract were evaluated roentgenographically by double blind technique in a total of 101 male human subjects. The results may briefly be summarized as follows: 1. There were significant differences on hypotonic rate being one of the indexes of the gastric tonus between timepidium-bromide and placebo. The effects of 3 experimental drugs were significantly high as compared with that of placebo on peristaltic movement of the stomach. The effect of timepidium-bromide was significantly different from that of placebo on the site of arrival of barium. 2. The comparison of degrees of the gastric tonus between main and control tests revealed that the effect of placebo obtained in the main test was significantly inferior to that of hyoscine-N-butylbromide obtained in the control test, whereas there existed no significant differences of the effects among 3 active drugs. 3. Effects of each drug on the gastric tonus which was scored by hypertonic, normotonic and hypotonic state were evaluated by stratification. The result showed that the effect of timepidium-bromide was significantly greater than that of placebo. 4. All active drugs were not significantly different in terms of 7 observed values each on the gastric form.", "contents": "Comparative studies of parasympatholytic drugs on stomach (double blind test) and analysis of relation between gastric form and tonus. Effects of 3 kinds of parasympatholytic drugs (timepidiumbromide, hyoscine-N-butylbromide and prifinium-bromide) and placebo (physiological saline solution) on the gastrointestinal tract were evaluated roentgenographically by double blind technique in a total of 101 male human subjects. The results may briefly be summarized as follows: 1. There were significant differences on hypotonic rate being one of the indexes of the gastric tonus between timepidium-bromide and placebo. The effects of 3 experimental drugs were significantly high as compared with that of placebo on peristaltic movement of the stomach. The effect of timepidium-bromide was significantly different from that of placebo on the site of arrival of barium. 2. The comparison of degrees of the gastric tonus between main and control tests revealed that the effect of placebo obtained in the main test was significantly inferior to that of hyoscine-N-butylbromide obtained in the control test, whereas there existed no significant differences of the effects among 3 active drugs. 3. Effects of each drug on the gastric tonus which was scored by hypertonic, normotonic and hypotonic state were evaluated by stratification. The result showed that the effect of timepidium-bromide was significantly greater than that of placebo. 4. All active drugs were not significantly different in terms of 7 observed values each on the gastric form."}
{"id": "PMID:1053", "title": "[Treatment of exocrine pancreatic insufficiency with fungal lipase (author's transl)].", "content": "7 patients suffering from severe exocrine pancreatic insufficiency have been treated with a lipolytic enzyme extracted from Rhizopus arrhizus. Comparing the fungal lipase with a placebo the drug lowered the daily stool weight from 809 g to 443 g on an average, i.e. by 45.2%. The steatorrhea was reduced from 75.6 g/24 h to 32.9 g, i.e. by 56.5%. When incubating the enzyme in vitro in saline solutions of different pH for 1 h the loss of lipolytic activity is 13% at pH 5, 15% at pH 4, and 19% at pH 3. So the enzyme, like fungal proteases, is almost not altered by hydrochloric acid at concentrations found physiologically in the stomach.", "contents": "[Treatment of exocrine pancreatic insufficiency with fungal lipase (author's transl)]. 7 patients suffering from severe exocrine pancreatic insufficiency have been treated with a lipolytic enzyme extracted from Rhizopus arrhizus. Comparing the fungal lipase with a placebo the drug lowered the daily stool weight from 809 g to 443 g on an average, i.e. by 45.2%. The steatorrhea was reduced from 75.6 g/24 h to 32.9 g, i.e. by 56.5%. When incubating the enzyme in vitro in saline solutions of different pH for 1 h the loss of lipolytic activity is 13% at pH 5, 15% at pH 4, and 19% at pH 3. So the enzyme, like fungal proteases, is almost not altered by hydrochloric acid at concentrations found physiologically in the stomach."}
{"id": "PMID:1076", "title": "Study of the sporulation of Bacillus thuringiensis var. thuringiensis.", "content": "During the submerged cultivation of Bacillus thuringiensis var. thuringiensis in 300- and 3000-liter fermentors, lysis occurred at the end of the exponential phase of growth. New vegetative cells were subsequently formed which usually sporulated. At time of lysis, the amount of soluble sugar was 1-12 g/liter, pH value dropped to 5.3-5.8 from the original PH 6.8 and started to rise after all the cells had lysed. The proteolytic activity was low during the lysis and increased as the sporulation commenced.", "contents": "Study of the sporulation of Bacillus thuringiensis var. thuringiensis. During the submerged cultivation of Bacillus thuringiensis var. thuringiensis in 300- and 3000-liter fermentors, lysis occurred at the end of the exponential phase of growth. New vegetative cells were subsequently formed which usually sporulated. At time of lysis, the amount of soluble sugar was 1-12 g/liter, pH value dropped to 5.3-5.8 from the original PH 6.8 and started to rise after all the cells had lysed. The proteolytic activity was low during the lysis and increased as the sporulation commenced."}
{"id": "PMID:1080", "title": "Some observations on the effects produced in white mice following the injection of certain suspensions of corroding bacilli.", "content": "Strictly anaerobic and facultatively anaerobic strains of \"corroding bacilli\" failed to produce any pathological symptoms when injected into white mice and no viable organisms could be recovered after 7 days. However, when these same strains were coupled with certain other living bacteria or certain sterile bacterial extracts, lesions developed from which corroding bacilli could be isolated even after 21 days.", "contents": "Some observations on the effects produced in white mice following the injection of certain suspensions of corroding bacilli. Strictly anaerobic and facultatively anaerobic strains of \"corroding bacilli\" failed to produce any pathological symptoms when injected into white mice and no viable organisms could be recovered after 7 days. However, when these same strains were coupled with certain other living bacteria or certain sterile bacterial extracts, lesions developed from which corroding bacilli could be isolated even after 21 days."}
{"id": "PMID:1081", "title": "Lysosomal hydrolases of the epidermis. 3. Peptide hydrolases.", "content": "Four distinct peptide hydrolases (EC 3-4) have been characterized in guinea-pig epidermis; these are cathepsin B1, cathepsin C, cathepsin D and arylamidase. Their properties are consistent with those of lysosomal enzymes. Cathepsin E was not detected.", "contents": "Lysosomal hydrolases of the epidermis. 3. Peptide hydrolases. Four distinct peptide hydrolases (EC 3-4) have been characterized in guinea-pig epidermis; these are cathepsin B1, cathepsin C, cathepsin D and arylamidase. Their properties are consistent with those of lysosomal enzymes. Cathepsin E was not detected."}
{"id": "PMID:1082", "title": "Micellar solubilization of fatty acids in aqueous media containing bile salts and phospholipids.", "content": "1. The solubility of fatty acids in aqueous media containing bile salts alone and in admixture with either lecithin (phosphatidylcholine) or phosphatidylethanolamine was determined. 2. Over the pH range 2-0-7-4, the order of fatty acid solubility in aqueous solutions containing bile salts was linoleic greater than oleic greater than elaidic greater than palmitic greater than stearic. The solubility of each fatty acid increased as the pH of the miceus solutions of bile salts greatly increased the solubility of palmitic acid and stearic acid. 4. In the presence of bile salts and lecithin, the solubility of oleic acid and elaidic acid decreased with increasing pH of the micellar solution, indicating a competitive effect between the fatty acid anions and lecithin. The solubility of linoleic acid increased linearly with lecithin concentration. 5. Phosphatidylethanolamine as an additive to bile salts increased the solubility of both saturated and unsaturated fatty acids in the pH range 2-3-7-4. The effectiveness of phosphatidylethanolamine as an amphiphile was similar to that of lecithin, although at pH 3.0 fatty acid solubility was greater in the presence of phosphatidylethanolamine. 6. The significance of these findings is discussed in relation to the intestinal absorption of fatty acids in sheep.", "contents": "Micellar solubilization of fatty acids in aqueous media containing bile salts and phospholipids. 1. The solubility of fatty acids in aqueous media containing bile salts alone and in admixture with either lecithin (phosphatidylcholine) or phosphatidylethanolamine was determined. 2. Over the pH range 2-0-7-4, the order of fatty acid solubility in aqueous solutions containing bile salts was linoleic greater than oleic greater than elaidic greater than palmitic greater than stearic. The solubility of each fatty acid increased as the pH of the miceus solutions of bile salts greatly increased the solubility of palmitic acid and stearic acid. 4. In the presence of bile salts and lecithin, the solubility of oleic acid and elaidic acid decreased with increasing pH of the micellar solution, indicating a competitive effect between the fatty acid anions and lecithin. The solubility of linoleic acid increased linearly with lecithin concentration. 5. Phosphatidylethanolamine as an additive to bile salts increased the solubility of both saturated and unsaturated fatty acids in the pH range 2-3-7-4. The effectiveness of phosphatidylethanolamine as an amphiphile was similar to that of lecithin, although at pH 3.0 fatty acid solubility was greater in the presence of phosphatidylethanolamine. 6. The significance of these findings is discussed in relation to the intestinal absorption of fatty acids in sheep."}
{"id": "PMID:1083", "title": "Influence of the products of phospholipolysis of phosphatidylcholine on micellar solubilization of fatty acids in the presence of bile salts.", "content": "1. The solubility of fatty acids in aqueous solutions containing bile salts and lysolecithin at pH values between 2-0 and 7-4 was studied. Both the 1-acyl and 2-acyl isomers of lysolecithin increased the solubility of fatty acids to the same extent, the order of solubility being linoleic greater than oleic greater than elaidic greater than palmitic greater than stearic. 2. The influence of the products of phospholipolysis of lecithin on palmitic acid solubility was determined. On a molar basis, lysolecithin was more effective than were bile salts in promoting the solubilization of the fatty acid. 3. In bile salt solutions in which the phospholipid concentration was constant on a molar basis, in solubility of palmitic acid decreased linearly with the progressive replacement of lecithin by lysolecithin. Palmitic acid was solubilized to the same extent on replacing lecithin with lysolecithin on a constant weight basis. 4. In bile salt solution containing lysolecithin and oleic acid in equimolar amounts, the solubility of palmitic acid was similar to that in bile salt solution containing lecithin in equivalent proportion. 5. The results are discussed in relation to the action of phospholipolytic activity on the intestinal absorption of fatty acids in sheep.", "contents": "Influence of the products of phospholipolysis of phosphatidylcholine on micellar solubilization of fatty acids in the presence of bile salts. 1. The solubility of fatty acids in aqueous solutions containing bile salts and lysolecithin at pH values between 2-0 and 7-4 was studied. Both the 1-acyl and 2-acyl isomers of lysolecithin increased the solubility of fatty acids to the same extent, the order of solubility being linoleic greater than oleic greater than elaidic greater than palmitic greater than stearic. 2. The influence of the products of phospholipolysis of lecithin on palmitic acid solubility was determined. On a molar basis, lysolecithin was more effective than were bile salts in promoting the solubilization of the fatty acid. 3. In bile salt solutions in which the phospholipid concentration was constant on a molar basis, in solubility of palmitic acid decreased linearly with the progressive replacement of lecithin by lysolecithin. Palmitic acid was solubilized to the same extent on replacing lecithin with lysolecithin on a constant weight basis. 4. In bile salt solution containing lysolecithin and oleic acid in equimolar amounts, the solubility of palmitic acid was similar to that in bile salt solution containing lecithin in equivalent proportion. 5. The results are discussed in relation to the action of phospholipolytic activity on the intestinal absorption of fatty acids in sheep."}
{"id": "PMID:1084", "title": "The purification and characterization of the low molecular weight human folate binding protein using affinity chromatography.", "content": "The low molecular weight folate binding protein (FABP) has been purified 1000-fold to a specific activity of 7.2 gamma g of pteroylglutamic acid (PGA) bound per mg of protein. This purified FABP represents two protein bands that bind PGA on polyacrylamide disc gel electrophoreis, elutes from DEAE-cellulose in 0.001 M phosphate buffer, stains positive with PAS, Elutes from concanavalin A Sepharose affinity columns with methyl alpha-mannoside, and shows three major peaks (pl =6.8, 7.5, 8.2) by isotric focusing. The binding of PGA to purified FABP dependent on pH and is inhibited by urea...", "contents": "The purification and characterization of the low molecular weight human folate binding protein using affinity chromatography. The low molecular weight folate binding protein (FABP) has been purified 1000-fold to a specific activity of 7.2 gamma g of pteroylglutamic acid (PGA) bound per mg of protein. This purified FABP represents two protein bands that bind PGA on polyacrylamide disc gel electrophoreis, elutes from DEAE-cellulose in 0.001 M phosphate buffer, stains positive with PAS, Elutes from concanavalin A Sepharose affinity columns with methyl alpha-mannoside, and shows three major peaks (pl =6.8, 7.5, 8.2) by isotric focusing. The binding of PGA to purified FABP dependent on pH and is inhibited by urea..."}
{"id": "PMID:1085", "title": "Studies on IgA and IgA monoclonal proteins derived from a single patient. Evidence for identical light chains and variable regions of the heavy chain.", "content": "Two immunoglobulins, IgA(K) and IgG(K), were isolated from the serum of a single patient with two monoclonal components (biclonal proteins). After chain separation, the light chains from each molecule were found to be identical by the following criteria: electrophoretic mobilities under various pH and dissociating conditions, amino acid compositon, fingerprint analysis of tryptic peptides and of 14C-succinylated chymotryptic peptides, and amino acid sequence of the N-terminal 40 residues. The heavy chains were indistinguishable for the N-terminal 45 amino acid residues. These data are consistent with the hypothesis that a single heavy chain variable (VH) region may be associated with two different heavy chain constant (CH) genes.", "contents": "Studies on IgA and IgA monoclonal proteins derived from a single patient. Evidence for identical light chains and variable regions of the heavy chain. Two immunoglobulins, IgA(K) and IgG(K), were isolated from the serum of a single patient with two monoclonal components (biclonal proteins). After chain separation, the light chains from each molecule were found to be identical by the following criteria: electrophoretic mobilities under various pH and dissociating conditions, amino acid compositon, fingerprint analysis of tryptic peptides and of 14C-succinylated chymotryptic peptides, and amino acid sequence of the N-terminal 40 residues. The heavy chains were indistinguishable for the N-terminal 45 amino acid residues. These data are consistent with the hypothesis that a single heavy chain variable (VH) region may be associated with two different heavy chain constant (CH) genes."}
{"id": "PMID:1086", "title": "Conformational properties of bovine plasma albumin with a cleaved internal peptide bond.", "content": "As shown previously, proteinases frequently associated with plasma albumin samples catalyze a very limited and specific cleavage of the albumin molecule when it exists in the F conformational state near pH 3.7. The primary proteolytic product, BPA, has a molecular weight similar to or identical with that of the parent protein but yields two large fragments of molecular weight approximately 46000 and 23000 on reduction. Evidence is presented here that cleavage occurs within the disulfide loop between Cys390 and Cys434 with no detectable loss of small peptides, the amino acid composition of BPA being identical with that of the parent protein within experimental error. Cleavage exposes a new amino-terminal phenylalanine residue and may occur at the Glx392-Phe393 bond although the possibility exists that it occurs at another X-Phe bond in the unsequenced region of residues 400-402. The damaged protein has a somewhat altered secondary structure as judged from optical rotatory dispersion and circular dichroism measurements, probably an approximate 15% loss in helicity. The hydrodynamic volume is increased by approximately 20%. However, various physical studies indicate the tertiary structure to be strikingly similar to that of the native protein. Of most significance is the fact that the protein still undergoes the N-F and N-B transitions, although in both cases they occur at somewhat more moderate pH than in the parent protein. Moreover a sensitivity of the N-B transition to Ca2+ is still seen and binding behavior toward the dye 8-anilino-1-naphthalenesulfonic acid is essentially unaltered. The results are best understood in terms of the concept of a multidomain structure which has been suggested frequently for plasma ablumin. Bond cleavage damages one domain but leaves the overall structure essentially unaltered except for some weakening of the interaction between domains.", "contents": "Conformational properties of bovine plasma albumin with a cleaved internal peptide bond. As shown previously, proteinases frequently associated with plasma albumin samples catalyze a very limited and specific cleavage of the albumin molecule when it exists in the F conformational state near pH 3.7. The primary proteolytic product, BPA, has a molecular weight similar to or identical with that of the parent protein but yields two large fragments of molecular weight approximately 46000 and 23000 on reduction. Evidence is presented here that cleavage occurs within the disulfide loop between Cys390 and Cys434 with no detectable loss of small peptides, the amino acid composition of BPA being identical with that of the parent protein within experimental error. Cleavage exposes a new amino-terminal phenylalanine residue and may occur at the Glx392-Phe393 bond although the possibility exists that it occurs at another X-Phe bond in the unsequenced region of residues 400-402. The damaged protein has a somewhat altered secondary structure as judged from optical rotatory dispersion and circular dichroism measurements, probably an approximate 15% loss in helicity. The hydrodynamic volume is increased by approximately 20%. However, various physical studies indicate the tertiary structure to be strikingly similar to that of the native protein. Of most significance is the fact that the protein still undergoes the N-F and N-B transitions, although in both cases they occur at somewhat more moderate pH than in the parent protein. Moreover a sensitivity of the N-B transition to Ca2+ is still seen and binding behavior toward the dye 8-anilino-1-naphthalenesulfonic acid is essentially unaltered. The results are best understood in terms of the concept of a multidomain structure which has been suggested frequently for plasma ablumin. Bond cleavage damages one domain but leaves the overall structure essentially unaltered except for some weakening of the interaction between domains."}
{"id": "PMID:1087", "title": "Detection and partial characterization of lipoprotein lipase in bovine aorta.", "content": "Extracts of acetone-ether powders of bovine thoracic aorta contain lipase activity which has an alkaline pH maximum (7.8-8.4) and is stimulated 4-10-fold by adding serum or isolated apolipoprotein-glutamate to the assay mixture. Serum activation is completely reversed by isolated apolipoprotein-serine or apolipoprotein-alanine. Lipolysis is strongly inhibited by NaCl (0.5 M) and protamine sulfate (1 mg/ml) and partially inhibited by heparin. Based on these characteristics, the lipase is identified as lipoprotein lipase.", "contents": "Detection and partial characterization of lipoprotein lipase in bovine aorta. Extracts of acetone-ether powders of bovine thoracic aorta contain lipase activity which has an alkaline pH maximum (7.8-8.4) and is stimulated 4-10-fold by adding serum or isolated apolipoprotein-glutamate to the assay mixture. Serum activation is completely reversed by isolated apolipoprotein-serine or apolipoprotein-alanine. Lipolysis is strongly inhibited by NaCl (0.5 M) and protamine sulfate (1 mg/ml) and partially inhibited by heparin. Based on these characteristics, the lipase is identified as lipoprotein lipase."}
{"id": "PMID:1088", "title": "Purine nucleotide pyrophosphotransferase from Streptomyces morookaensis, capable of synthesizing pppApp and pppGpp.", "content": "Purine nucleotide pyrophosphotransferase was purified to apparent homogeneity from a culture filtrate of Streptomyces morookaensis. It is a monomeric protein with a molecular weight of 24 000-25 000, and its isoelectric point is 6.9. The enzyme synthesizes purine nucleoside 5'-phosphate (mono, di, or tri) 3'-diphosphates such as pppApp, ppApp, pApp, pppGpp, ppGpp and pppIpp by transferring a pyrophosphoryl group from the 5'-position of ATP, dATP and ppApp to the 3'-position of purine nucleotides. The purified enzyme catalysed the formation of 435 mumol of pppApp and 620 mumol of pppGpp from ATP and GTP per min mg protein under the standard conditions. The enzyme requires absolutely a divalent cation for activity, and optimum pH for the enzyme activity lay above 10 for Mg2+, for Co2+ and Zn2+ from 9 to 9.5, and for Fe2+ from 7.5 to 8. The following Michaelis constants were determined: AMP, 2.78 mM; ADP, 3.23 mM; GMP, 0.89 mM; GDP, 0.46 mM and GTP, 1.54 mM, in the case of ATP donor. The enzyme is inhibited by guanine, guanosine, dGDP, dGTP, N-bromosuccinimide, iodacetate, sodium borate and mercuric acetate.", "contents": "Purine nucleotide pyrophosphotransferase from Streptomyces morookaensis, capable of synthesizing pppApp and pppGpp. Purine nucleotide pyrophosphotransferase was purified to apparent homogeneity from a culture filtrate of Streptomyces morookaensis. It is a monomeric protein with a molecular weight of 24 000-25 000, and its isoelectric point is 6.9. The enzyme synthesizes purine nucleoside 5'-phosphate (mono, di, or tri) 3'-diphosphates such as pppApp, ppApp, pApp, pppGpp, ppGpp and pppIpp by transferring a pyrophosphoryl group from the 5'-position of ATP, dATP and ppApp to the 3'-position of purine nucleotides. The purified enzyme catalysed the formation of 435 mumol of pppApp and 620 mumol of pppGpp from ATP and GTP per min mg protein under the standard conditions. The enzyme requires absolutely a divalent cation for activity, and optimum pH for the enzyme activity lay above 10 for Mg2+, for Co2+ and Zn2+ from 9 to 9.5, and for Fe2+ from 7.5 to 8. The following Michaelis constants were determined: AMP, 2.78 mM; ADP, 3.23 mM; GMP, 0.89 mM; GDP, 0.46 mM and GTP, 1.54 mM, in the case of ATP donor. The enzyme is inhibited by guanine, guanosine, dGDP, dGTP, N-bromosuccinimide, iodacetate, sodium borate and mercuric acetate."}
{"id": "PMID:1089", "title": "Protein kinase in cultured plant cells.", "content": "A protein kinase (EC 2.7.1.37) which phosphorylates histones was purified partially from the soluble fractions of cultured plant cells. The optimum pH was 7.5 to 9.0. The activity wasnot stimulated by exogeneous cyclic AMP. It was thermolabile and completely dependent on the presence of Mg2+ or Mn2+ for activity. p-Chloromercuribenzoate inactivated this enzyme and this inactivation was overcome by mercaptoethanol.", "contents": "Protein kinase in cultured plant cells. A protein kinase (EC 2.7.1.37) which phosphorylates histones was purified partially from the soluble fractions of cultured plant cells. The optimum pH was 7.5 to 9.0. The activity wasnot stimulated by exogeneous cyclic AMP. It was thermolabile and completely dependent on the presence of Mg2+ or Mn2+ for activity. p-Chloromercuribenzoate inactivated this enzyme and this inactivation was overcome by mercaptoethanol."}
{"id": "PMID:1090", "title": "Adenosine triphosphate: nicotinamide mononucleotide adenylyltransferase of pig liver. Purification and properties.", "content": "Adenosine triphosphate : nicotinamide mononucleotide adenylyltransferase (EC 2.7.7.1) has been purifiec approximately 3500-fold from an extract of pig liver nuclei to a specific activity of 40 mumol of NAD+ per min per mg protein. The enzyme was found to have a molecular weight of 203 000, a frictional ratio of 1.6 and an isoelectric point of approximately 5. Michaelis constants for ATP and NMN were 0.11 mM and 0.12 mM, respectively.", "contents": "Adenosine triphosphate: nicotinamide mononucleotide adenylyltransferase of pig liver. Purification and properties. Adenosine triphosphate : nicotinamide mononucleotide adenylyltransferase (EC 2.7.7.1) has been purifiec approximately 3500-fold from an extract of pig liver nuclei to a specific activity of 40 mumol of NAD+ per min per mg protein. The enzyme was found to have a molecular weight of 203 000, a frictional ratio of 1.6 and an isoelectric point of approximately 5. Michaelis constants for ATP and NMN were 0.11 mM and 0.12 mM, respectively."}
{"id": "PMID:1091", "title": "Phospholipase A2 isoenzyme from porcine pancreas. Purification and some properties.", "content": "Porcine pancreas synthesizes a prephospholipase A2 which occurs in a 5 : 95 ratio compared with the more abundant zymogen of the same enzyme (phosphatide-acylhydrolase; EC 3.1.1.4). These two prephospholipases could be well separated by CM-cellulose chromatography. Both the active and the zymogen form of the isoenzyme were isolated and purified. The activation peptides of both prephospholipases appeared to be identical, while the active enzymes showed a few interesting differences. The most striking differences were the loss of one histidine and one methionine in the isoenzyme, corresponding to residues 24 and 27, respectively, in alpha-phospholipase A2. The positional and stereo specificity of both enzymes are the same, but the specific activity of the beta-phospholipase A2 is lower. The molecular weight of the isoenzyme was estimated to be about 14 000, while the isoelectric points were 5.1 and 5.9 for the isoprecursor and active isoenzyme, respectively.", "contents": "Phospholipase A2 isoenzyme from porcine pancreas. Purification and some properties. Porcine pancreas synthesizes a prephospholipase A2 which occurs in a 5 : 95 ratio compared with the more abundant zymogen of the same enzyme (phosphatide-acylhydrolase; EC 3.1.1.4). These two prephospholipases could be well separated by CM-cellulose chromatography. Both the active and the zymogen form of the isoenzyme were isolated and purified. The activation peptides of both prephospholipases appeared to be identical, while the active enzymes showed a few interesting differences. The most striking differences were the loss of one histidine and one methionine in the isoenzyme, corresponding to residues 24 and 27, respectively, in alpha-phospholipase A2. The positional and stereo specificity of both enzymes are the same, but the specific activity of the beta-phospholipase A2 is lower. The molecular weight of the isoenzyme was estimated to be about 14 000, while the isoelectric points were 5.1 and 5.9 for the isoprecursor and active isoenzyme, respectively."}
{"id": "PMID:1092", "title": "Cylic nucleotide phosphodiesterase in silkworm. Characterization of cyclic GMP phosphodiesterase.", "content": "The existence of cyclic GMP phosphodiesterase (EC 3.1.4.-) was demonstrated in silkworm larva by gel filtration of the homogenate. The cyclic GMP phosphodiesterase was separated from cyclic AMP phosphodiesterases by column chromatography on hydroxyapatite and Sephadex G-200. The enzyme has a molecular weight of approx. 260 000, and optimum pH of 8.3 and a Km value of 2 muM. The enzyme is activated by 5 mM of Mg2+ and 2 mM of Mn2+. The cyclic GMP phosphodiesterase activity was greatly inhibited by low concentrations of cyclic IMP but to a lesser extent by cyclic AMP even at a high concentration. The activity was also inhibited by caffeine and theophylline.", "contents": "Cylic nucleotide phosphodiesterase in silkworm. Characterization of cyclic GMP phosphodiesterase. The existence of cyclic GMP phosphodiesterase (EC 3.1.4.-) was demonstrated in silkworm larva by gel filtration of the homogenate. The cyclic GMP phosphodiesterase was separated from cyclic AMP phosphodiesterases by column chromatography on hydroxyapatite and Sephadex G-200. The enzyme has a molecular weight of approx. 260 000, and optimum pH of 8.3 and a Km value of 2 muM. The enzyme is activated by 5 mM of Mg2+ and 2 mM of Mn2+. The cyclic GMP phosphodiesterase activity was greatly inhibited by low concentrations of cyclic IMP but to a lesser extent by cyclic AMP even at a high concentration. The activity was also inhibited by caffeine and theophylline."}
{"id": "PMID:1093", "title": "Glucanases in Schizosaccharomyces. Isolation and properties of an exo-beta-glucanase from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis.", "content": "(11 Cell extracts and extracellular culture fluids of species of the yeast genus Schizosaccharomyces exhibited exo-beta-(1 leads to 3)- and exo-beta-(1 leads to 6)-glucanase (EC 3.2.1.-) activities. (2) Using a combination of Sephadex G-100 and DEAE-cellulose chromatography, the exo-beta-(1 leads to 3)-glucanases from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis were purified extensively. The enzymes from either location exhibited similar purification and other properties. (3) The purified enzymes hydrolysed the beta-(1 leads to 6)-glucosidic linkage in addition to the beta-(1 leads to 3) linkage. Heat denaturation, inhibition and electrophoretic studies indicated that both hydrolytic activities were properties of a single protein. Laminarin and pustulan hydrolysis followed Michaelis-Menten kinetics. The Km and V for laminarin hydrolysis were 6.25 mg/ml and 350 mumol of glucose released/min/mg protein, and for pustulan they were 166 mg/ml and 52 mumol of glucose released/min/mg protein. (4) The exo-beta-glucanase was assigned a molecular weight of 43 000. (5) the purified enzyme failed to hydrolyse isolated cell walls from either baker's yeast or Schizosaccharomyces pombe or to induce protoplast formation from intact cells of S. japonicus var. versatilis or Saccharomyces cerevisiae.", "contents": "Glucanases in Schizosaccharomyces. Isolation and properties of an exo-beta-glucanase from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis. (11 Cell extracts and extracellular culture fluids of species of the yeast genus Schizosaccharomyces exhibited exo-beta-(1 leads to 3)- and exo-beta-(1 leads to 6)-glucanase (EC 3.2.1.-) activities. (2) Using a combination of Sephadex G-100 and DEAE-cellulose chromatography, the exo-beta-(1 leads to 3)-glucanases from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis were purified extensively. The enzymes from either location exhibited similar purification and other properties. (3) The purified enzymes hydrolysed the beta-(1 leads to 6)-glucosidic linkage in addition to the beta-(1 leads to 3) linkage. Heat denaturation, inhibition and electrophoretic studies indicated that both hydrolytic activities were properties of a single protein. Laminarin and pustulan hydrolysis followed Michaelis-Menten kinetics. The Km and V for laminarin hydrolysis were 6.25 mg/ml and 350 mumol of glucose released/min/mg protein, and for pustulan they were 166 mg/ml and 52 mumol of glucose released/min/mg protein. (4) The exo-beta-glucanase was assigned a molecular weight of 43 000. (5) the purified enzyme failed to hydrolyse isolated cell walls from either baker's yeast or Schizosaccharomyces pombe or to induce protoplast formation from intact cells of S. japonicus var. versatilis or Saccharomyces cerevisiae."}
{"id": "PMID:1094", "title": "Purification and some properties of a novel maltohexaose-producing exo-amylase from Aerobacter aerogenes.", "content": "Maltohexaose producing amylase (EC 3.2.1.-) is the fourth known exo-amylase, the three previously known being glucoamylase, beta-amylase and Pseudomonas stutzeri maltotetraose producing amylase. The enzyme after release from Aerobacter aerogenes cells by 0.1% sodium lauryl sulfate extraction was purified by ammonium sulfate precipitation, DEAE-Sephadex column chromatography and Sephadex G-100 gel filtration to 80-fold of the original sodium lauryl sulfate extract activity, It gave a single band on disc electrophoresis, and the molecular weight by gel filtration was 54 000. This amylase showed maximal activity at 50 degrees C and pH 6.80. The pH stability range was relatively wide, the enzyme retaining more than 90% of its initial activity in the range of 6.50-9.0. 80% of the activity was retained after 15 min at 50 degrees C. This enzyme produced maltohexaose from starch, amylose and amylopectin by exo-attack, but did not act on alpha- or beta-cyclodextrin, pullulan or maltohexaitol. Also the enzyme acted on beta-limit dextrins of amylopectin and glycogen to form branched oligosaccharides. The unusual reaction of this enzyme on beta-limit dextrin is discussed from the standpoint of the stereochemistry of 1,4-alpha- and 1,6-alpha-glucosidic bonds. This is the anomalous amylase for which it is recognized that 1,6-alpha-glucosidic linkages in the substrates can mimic the effect of 1,4-alpha-bonds, as previously observed in pseudo-priming reactions of E. coli phosphorylase.", "contents": "Purification and some properties of a novel maltohexaose-producing exo-amylase from Aerobacter aerogenes. Maltohexaose producing amylase (EC 3.2.1.-) is the fourth known exo-amylase, the three previously known being glucoamylase, beta-amylase and Pseudomonas stutzeri maltotetraose producing amylase. The enzyme after release from Aerobacter aerogenes cells by 0.1% sodium lauryl sulfate extraction was purified by ammonium sulfate precipitation, DEAE-Sephadex column chromatography and Sephadex G-100 gel filtration to 80-fold of the original sodium lauryl sulfate extract activity, It gave a single band on disc electrophoresis, and the molecular weight by gel filtration was 54 000. This amylase showed maximal activity at 50 degrees C and pH 6.80. The pH stability range was relatively wide, the enzyme retaining more than 90% of its initial activity in the range of 6.50-9.0. 80% of the activity was retained after 15 min at 50 degrees C. This enzyme produced maltohexaose from starch, amylose and amylopectin by exo-attack, but did not act on alpha- or beta-cyclodextrin, pullulan or maltohexaitol. Also the enzyme acted on beta-limit dextrins of amylopectin and glycogen to form branched oligosaccharides. The unusual reaction of this enzyme on beta-limit dextrin is discussed from the standpoint of the stereochemistry of 1,4-alpha- and 1,6-alpha-glucosidic bonds. This is the anomalous amylase for which it is recognized that 1,6-alpha-glucosidic linkages in the substrates can mimic the effect of 1,4-alpha-bonds, as previously observed in pseudo-priming reactions of E. coli phosphorylase."}
{"id": "PMID:1095", "title": "Inhibition of human liver beta-galactosidases and beta-glucosidase by n-bromoacetyl-beta-D-galactosylamine.", "content": "N-Bromoacetyl-beta-D-galactosylamine is an irreversible inhibitor of the 'acid' and the 'neutral' beta-galactosidases (beta-D-galactoside galactohydrolase, EC 3.2.1.23) of human liver. The inactivation of acid beta-galactosidase appears to involve a group with a pKa = 4.5. The inhibition of neutral beta-galactosidase only occurs above pH 8.0. Both enzymes are protected against inhibition by the presence of substrates, suggesting that the inhibitor reacts with the active site of the enzymes. Other lysosomal hydrolases are not inhibited by N-bromoacetyl-beta-D-galactosylamine, with the exception of 'neutral' beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21). The pH dependence of neutral beta-glucosidase inactivation is essentially identical to that of the neutral beta-galactosidase. Inhibition of beta-glucosidase by this galactose derivative suggests that the same enzyme may bind glucosides and galactosides. Furthermore, both neutral beta-galactosidase and beta-glucosidase are inactivated at 52 degrees C with a half-life of 7.5 min. The presence of a single enzyme with both beta-glucosidase and beta-galactosidase activities is also supported by mixed-substrate experiments.", "contents": "Inhibition of human liver beta-galactosidases and beta-glucosidase by n-bromoacetyl-beta-D-galactosylamine. N-Bromoacetyl-beta-D-galactosylamine is an irreversible inhibitor of the 'acid' and the 'neutral' beta-galactosidases (beta-D-galactoside galactohydrolase, EC 3.2.1.23) of human liver. The inactivation of acid beta-galactosidase appears to involve a group with a pKa = 4.5. The inhibition of neutral beta-galactosidase only occurs above pH 8.0. Both enzymes are protected against inhibition by the presence of substrates, suggesting that the inhibitor reacts with the active site of the enzymes. Other lysosomal hydrolases are not inhibited by N-bromoacetyl-beta-D-galactosylamine, with the exception of 'neutral' beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21). The pH dependence of neutral beta-glucosidase inactivation is essentially identical to that of the neutral beta-galactosidase. Inhibition of beta-glucosidase by this galactose derivative suggests that the same enzyme may bind glucosides and galactosides. Furthermore, both neutral beta-galactosidase and beta-glucosidase are inactivated at 52 degrees C with a half-life of 7.5 min. The presence of a single enzyme with both beta-glucosidase and beta-galactosidase activities is also supported by mixed-substrate experiments."}
{"id": "PMID:1096", "title": "Endo-arabinanase from Bacillus subtilis F-11.", "content": "An arabinanase was purified from the culture fluid of Bacillus subtilis F-11. The process was as follows: salting out by (NH4)2SO4, repeated chromatography on hydroxy apatite and gel filtration on Sepharose-6B. The purified enzyme was demonstrated to be homogeneous by disc electrophoresis. The enzyme was found to be active on arabinan and 1,5-arabinan, but inactive on phenyl alpha-L-arabinofuranoside, p-nitrophenyl beta-D-galactopyranoside, arabinoxylan, gum arabic. The enzyme released arabinose, arabinobiose, arabinotriose and higher oligosaccharides during the course of hydrolysis of 1,5-arabinan. The end products were found to be arabinose and arabinobiose after 144 h of hydrolysis.", "contents": "Endo-arabinanase from Bacillus subtilis F-11. An arabinanase was purified from the culture fluid of Bacillus subtilis F-11. The process was as follows: salting out by (NH4)2SO4, repeated chromatography on hydroxy apatite and gel filtration on Sepharose-6B. The purified enzyme was demonstrated to be homogeneous by disc electrophoresis. The enzyme was found to be active on arabinan and 1,5-arabinan, but inactive on phenyl alpha-L-arabinofuranoside, p-nitrophenyl beta-D-galactopyranoside, arabinoxylan, gum arabic. The enzyme released arabinose, arabinobiose, arabinotriose and higher oligosaccharides during the course of hydrolysis of 1,5-arabinan. The end products were found to be arabinose and arabinobiose after 144 h of hydrolysis."}
{"id": "PMID:1097", "title": "Aminopeptidases in webbing clothes moth larvae. Properties and specificities of the enzymes of intermediate electrophoretic mobility.", "content": "The major group of aminopeptidases (EC 3.4.11.-) of intermediate electrophoretic mobility, from Tineola bisselliella larvae, hav been fractionated into six bands by preparative polyacrylamide gel electrophoresis and the properties of these fractions investigated. They resemble each other in their pH optima of 8.2, their molecular weight of 240 000, their responses to various active site inhibitors and metal cations, and their specificities towards seventeen L-amino-acyl-beta-naphthylamide substrates. The derivatives of methionine, leucine, alanine, lysine, arginine and glutamic acid were those most rapidly hydrolysed. They appear to be true aminopeptidases hydrolysing amino acid amides, dipeptides and oligopeptides from the N-terminal end.", "contents": "Aminopeptidases in webbing clothes moth larvae. Properties and specificities of the enzymes of intermediate electrophoretic mobility. The major group of aminopeptidases (EC 3.4.11.-) of intermediate electrophoretic mobility, from Tineola bisselliella larvae, hav been fractionated into six bands by preparative polyacrylamide gel electrophoresis and the properties of these fractions investigated. They resemble each other in their pH optima of 8.2, their molecular weight of 240 000, their responses to various active site inhibitors and metal cations, and their specificities towards seventeen L-amino-acyl-beta-naphthylamide substrates. The derivatives of methionine, leucine, alanine, lysine, arginine and glutamic acid were those most rapidly hydrolysed. They appear to be true aminopeptidases hydrolysing amino acid amides, dipeptides and oligopeptides from the N-terminal end."}
{"id": "PMID:1098", "title": "Studies on an activator of the (Ca2+ plus Mg2+)-ATPase of human erythrocyte membranes.", "content": "1. An activator of the (Ca2+ plus Mg2+)-stimulated ATPase present in the human erythrocytes (membrane) has been isolated in soluble form from hemolysates of these cells. Partial purification has been achieved through use of carboxymethyl-Sephadex chromatography. The resulting activator fraction contained no hemoglobin and only 0.3% of the total adenylate kinase activity of the cell. 2. Whereas the activator was released from erythrocytes subjected to hemolysis in 20 miosM buffer at pH 7.6 or at pH 5.8, only the membranes prepared at pH 7.6 were affected by it. 2. Whereas the activator was released from erythrocytes subjected to hemolysis in 20 miosM buffer at pH 7.6 or at pH 5.8, only the membranes prepared at pH 7.6 were affected by it. 3. When (Ca2+ plus Mg2+)-ATPase activity was measured by 32Pi release from (gamma-32P)ATP, freeze-thawed erythrocytes, as well as membranes prepared at pH 5.8 and at pH 7.6, expressed lower values than noted by assay for total Pi release. When ADP instead of ATP was used as substrate, significant amount of Pi were released by these erythrocyte preparations. Further study revealed (a) production of ATP and AMP from ADP with membranes and hemolysate alone, and (b) exchange of the gamma-and B-position phosphate on (gama-32P)ATP in the presence of membranes plus hemolysates. These observations established the presence of adenylate kinase activity in the (membrane-free) hemolysates and in membranes. It further supports the conclusion that Pi release from ADP by human erythrocytes (freeze-thawed) and by their isolated membranes is due to formation of ATP by adenylate kinase and hydrolysis of this generated ATP by (Ca2+ plus Mg2+)-ATPase. 4. The following points were also established: (a) absence of an ADPase in human erythrocytes; (b) the (Ca2+ plus Mg2+)-ATPase activator enhanced cleavage only of the gama-position of ATP and (c) the (Ca2+ plus Mg2+)-ATPase activator is neither adenylate kinase nor hemoglobin.", "contents": "Studies on an activator of the (Ca2+ plus Mg2+)-ATPase of human erythrocyte membranes. 1. An activator of the (Ca2+ plus Mg2+)-stimulated ATPase present in the human erythrocytes (membrane) has been isolated in soluble form from hemolysates of these cells. Partial purification has been achieved through use of carboxymethyl-Sephadex chromatography. The resulting activator fraction contained no hemoglobin and only 0.3% of the total adenylate kinase activity of the cell. 2. Whereas the activator was released from erythrocytes subjected to hemolysis in 20 miosM buffer at pH 7.6 or at pH 5.8, only the membranes prepared at pH 7.6 were affected by it. 2. Whereas the activator was released from erythrocytes subjected to hemolysis in 20 miosM buffer at pH 7.6 or at pH 5.8, only the membranes prepared at pH 7.6 were affected by it. 3. When (Ca2+ plus Mg2+)-ATPase activity was measured by 32Pi release from (gamma-32P)ATP, freeze-thawed erythrocytes, as well as membranes prepared at pH 5.8 and at pH 7.6, expressed lower values than noted by assay for total Pi release. When ADP instead of ATP was used as substrate, significant amount of Pi were released by these erythrocyte preparations. Further study revealed (a) production of ATP and AMP from ADP with membranes and hemolysate alone, and (b) exchange of the gamma-and B-position phosphate on (gama-32P)ATP in the presence of membranes plus hemolysates. These observations established the presence of adenylate kinase activity in the (membrane-free) hemolysates and in membranes. It further supports the conclusion that Pi release from ADP by human erythrocytes (freeze-thawed) and by their isolated membranes is due to formation of ATP by adenylate kinase and hydrolysis of this generated ATP by (Ca2+ plus Mg2+)-ATPase. 4. The following points were also established: (a) absence of an ADPase in human erythrocytes; (b) the (Ca2+ plus Mg2+)-ATPase activator enhanced cleavage only of the gama-position of ATP and (c) the (Ca2+ plus Mg2+)-ATPase activator is neither adenylate kinase nor hemoglobin."}
{"id": "PMID:1099", "title": "[Acid and alkaline denaturation of superoxide dismutase].", "content": "Optical and ESR spectra of erythrocyte superoxide dismutase denaturated with acid and alkali are described. Sharp changes in activity and spectra were found. \"Residual\" activity of alkaline denaturated protein was higher than of acidic denaturated sample. It is suggested that covalent bonding copper-nitrogen is essential for superoxide dismutase activity of the protein or synthetic copper complexes.", "contents": "[Acid and alkaline denaturation of superoxide dismutase]. Optical and ESR spectra of erythrocyte superoxide dismutase denaturated with acid and alkali are described. Sharp changes in activity and spectra were found. \"Residual\" activity of alkaline denaturated protein was higher than of acidic denaturated sample. It is suggested that covalent bonding copper-nitrogen is essential for superoxide dismutase activity of the protein or synthetic copper complexes."}
{"id": "PMID:1100", "title": "[Light scattering by cell suspensions in normal conditions and exposed to external factors].", "content": "The characteristics of light scattering of cell suspensions in norm (pH 7,2, t=20degreesC) and upon external influences (change of pH and increase of tdegree). The turbidity tauapproximatelylambda-n and n=0,2--0,3 for cells in norm. After cell damage n increases. Dependence of n correlates with the increase of some injured cells determined by eozin test. Alterations of light scattering after cell damage were connected with the increase of deposit of intercellular structure in general scattering.", "contents": "[Light scattering by cell suspensions in normal conditions and exposed to external factors]. The characteristics of light scattering of cell suspensions in norm (pH 7,2, t=20degreesC) and upon external influences (change of pH and increase of tdegree). The turbidity tauapproximatelylambda-n and n=0,2--0,3 for cells in norm. After cell damage n increases. Dependence of n correlates with the increase of some injured cells determined by eozin test. Alterations of light scattering after cell damage were connected with the increase of deposit of intercellular structure in general scattering."}
{"id": "PMID:1103", "title": "[The fragmentation and reconstruction of the oligomycin-sensitive ATPase system of liver mitochondria].", "content": "The protein and proteolipid complexes and oligomycin insensitive soluble ATPase were prepared from rat liver mitochondria. The incubation of soluble ATPase with protein and proteolipid complexes resulted in restoration of ATPase sensitivity to oligomycin at room temperature. The process of reconstruction depended on pH, incubation time, temperature and other conditions.", "contents": "[The fragmentation and reconstruction of the oligomycin-sensitive ATPase system of liver mitochondria]. The protein and proteolipid complexes and oligomycin insensitive soluble ATPase were prepared from rat liver mitochondria. The incubation of soluble ATPase with protein and proteolipid complexes resulted in restoration of ATPase sensitivity to oligomycin at room temperature. The process of reconstruction depended on pH, incubation time, temperature and other conditions."}
{"id": "PMID:1104", "title": "[Study of acetyl-CoA-synthetase from staphylococcus aureus].", "content": "Acetyl-CoA-synthetase was isolated from cells of St. aureus 209-P. The method of isolation and partial purification of the enzyme is worked out. Km values of the enzyme for acetate, CoA and ATP are calculated. p-Chloromercuribenzoate and monoiodoacetate were shown to inhibit the enzyme activity. The enzyme activity is estimated depending on the age of the cell culture and on the presence of acetate in the culture medium.", "contents": "[Study of acetyl-CoA-synthetase from staphylococcus aureus]. Acetyl-CoA-synthetase was isolated from cells of St. aureus 209-P. The method of isolation and partial purification of the enzyme is worked out. Km values of the enzyme for acetate, CoA and ATP are calculated. p-Chloromercuribenzoate and monoiodoacetate were shown to inhibit the enzyme activity. The enzyme activity is estimated depending on the age of the cell culture and on the presence of acetate in the culture medium."}
{"id": "PMID:1105", "title": "[Effect of prosthetic group of horseradish peroxidase on enzyme stability].", "content": "Constants of inactivation rate of horseradish peroxidase (HRP) apo-HRP and apo-HRP-protoporphyrin (PP) are estimated at the pH range 2.8-12.8 and 25 degrees C. Two ionogenic groups (acid and alkaline) are detected on cases of HRP and apo-HRP, which are responsible for stable HRP conformation. HRP stability within the pH range 5-10 exceeded 30 times that of apo-HRP, while the stability apo-HRP-PP complex is similar to that of apo-HRP. The data obtained show that formation of complex of apo-HRP with PP, an analogue of the prostetic group lacking central Fe atom, practically does not affect the stability of HRP protein globula at pH 5-10, but significantly stabylized apo-HRP at the extreme pH values. The complex formation of apo-HRP with active prosthetic group - hemin - results on the stable conformation of the HRP protein globula, which suggests a determining role of Fe ion - porphyrin complex (hemin) on the support of the stable HRP structure.", "contents": "[Effect of prosthetic group of horseradish peroxidase on enzyme stability]. Constants of inactivation rate of horseradish peroxidase (HRP) apo-HRP and apo-HRP-protoporphyrin (PP) are estimated at the pH range 2.8-12.8 and 25 degrees C. Two ionogenic groups (acid and alkaline) are detected on cases of HRP and apo-HRP, which are responsible for stable HRP conformation. HRP stability within the pH range 5-10 exceeded 30 times that of apo-HRP, while the stability apo-HRP-PP complex is similar to that of apo-HRP. The data obtained show that formation of complex of apo-HRP with PP, an analogue of the prostetic group lacking central Fe atom, practically does not affect the stability of HRP protein globula at pH 5-10, but significantly stabylized apo-HRP at the extreme pH values. The complex formation of apo-HRP with active prosthetic group - hemin - results on the stable conformation of the HRP protein globula, which suggests a determining role of Fe ion - porphyrin complex (hemin) on the support of the stable HRP structure."}
{"id": "PMID:1106", "title": "[Wheat protein disulfide reductase].", "content": "Proteindisulphide reductase is isolated and partially purified from wheat seedlings and some properties of the enzyme are studied: pH optimum is 7.4; temperature optimum - 37 degrees C; Km = 2.6-10(-4)M for the substrate (wheat albumin); Km = 7.5-10(-5) M for coenzyme (NADP-H). The enzyme is specific for NADP-H and is not active in the presence of NAD-H. Maximal activity of proteindisulphide reductase is developed in anaerobic conditions. A technique of the estimation of proteindisulphide reductase activity using wheat albumin as a substrate is worked out. The enzyme activity decreases regularly in the corn ripening and increases under germination. It is accompanied by the respective increase or decrease in the amount of disulphide bonds in gluten protein and by changes of physico-chemical characteristics of gluten. Incubation of gluten with the enzyme preparation affects reological properties of gluten (it becomes weaker) and decreases the gluten viscosity of gluten solution.", "contents": "[Wheat protein disulfide reductase]. Proteindisulphide reductase is isolated and partially purified from wheat seedlings and some properties of the enzyme are studied: pH optimum is 7.4; temperature optimum - 37 degrees C; Km = 2.6-10(-4)M for the substrate (wheat albumin); Km = 7.5-10(-5) M for coenzyme (NADP-H). The enzyme is specific for NADP-H and is not active in the presence of NAD-H. Maximal activity of proteindisulphide reductase is developed in anaerobic conditions. A technique of the estimation of proteindisulphide reductase activity using wheat albumin as a substrate is worked out. The enzyme activity decreases regularly in the corn ripening and increases under germination. It is accompanied by the respective increase or decrease in the amount of disulphide bonds in gluten protein and by changes of physico-chemical characteristics of gluten. Incubation of gluten with the enzyme preparation affects reological properties of gluten (it becomes weaker) and decreases the gluten viscosity of gluten solution."}
{"id": "PMID:1107", "title": "[Modification of pancreatic ribonuclease activity in complexes with polyanions].", "content": "Carboxymethylcellulose, carboxymethylchitin, sulfoethylcellulose and dextrane sulfate interact with pancreatic ribonuclease. In comparison with ribonuclease activity the activity of formed complexes changes differently at the stages of transesterification and hydrolysis, and at each stage the effect of polymers on ribonuclease activity essentially differs. The use of ribonuclease-dextrane sulfate complex in the reaction of uridylyl-(3' leads to 5')-cytidine synthesis demonstrated that the protein synthetic activity completely retained when hydrolytic activity was considerably suppressed.", "contents": "[Modification of pancreatic ribonuclease activity in complexes with polyanions]. Carboxymethylcellulose, carboxymethylchitin, sulfoethylcellulose and dextrane sulfate interact with pancreatic ribonuclease. In comparison with ribonuclease activity the activity of formed complexes changes differently at the stages of transesterification and hydrolysis, and at each stage the effect of polymers on ribonuclease activity essentially differs. The use of ribonuclease-dextrane sulfate complex in the reaction of uridylyl-(3' leads to 5')-cytidine synthesis demonstrated that the protein synthetic activity completely retained when hydrolytic activity was considerably suppressed."}
{"id": "PMID:1108", "title": "[Kinetics and mechanism of action of horseradish peroxidase in the reaction of dioxyfumaric acid oxidation with atmospheric oxygen].", "content": "Quantitative kinetic data are given on the oxidation reaction of dioxyfumaric acid (DFA) with atmospheric oxygen in the presence of horseradish peroxidase (HRP) depending on pH. Activation constants of oxidation with hydrogen peroxide and Mn ions are determined at pH 3.0. Autocatalytic character of FRA oxidation is shown to be due to the formation of H2O2 and other hydro peroxide-type compounds in the reaction, HRP convertions in the DFA--O2 system are studied using spectrophotometry. A mechanism of the initiation of free radicals in HRP--DFA--O2 system is proposed.", "contents": "[Kinetics and mechanism of action of horseradish peroxidase in the reaction of dioxyfumaric acid oxidation with atmospheric oxygen]. Quantitative kinetic data are given on the oxidation reaction of dioxyfumaric acid (DFA) with atmospheric oxygen in the presence of horseradish peroxidase (HRP) depending on pH. Activation constants of oxidation with hydrogen peroxide and Mn ions are determined at pH 3.0. Autocatalytic character of FRA oxidation is shown to be due to the formation of H2O2 and other hydro peroxide-type compounds in the reaction, HRP convertions in the DFA--O2 system are studied using spectrophotometry. A mechanism of the initiation of free radicals in HRP--DFA--O2 system is proposed."}
{"id": "PMID:1109", "title": "[Some physical and chemical properties of serinesulfhydrase from chicken liver].", "content": "An improved procedure of purification of serinesulfhydrase from chicken liver is described. Preparations of enzyme (700-fold purification with the yield of 40 per cent from total activity) have been obtained homogeneous on polyacrylamide gel electrophoresis. Molecular weight of serinesulfhydrase is 90.000; 1 mole of enzyme contains 2 moles of pyridoxalphosphate and consists apparently of 2 subunits. Amino acid composition of the enzyme is studied. Absorption spectrum of serinesulfhydrase has a maximum at 430 nm what is characteristic of numerous pyridoxal-P enzymes. The position of this maximum does not depend on pH (within its range 6--10) and the presence of  L-serine, a primary enzyme substrate. An essential change in the absorption spectrum of enzyme was observed in the presence of some thiol compound--DL-homocysteine, beta-mercaptoethanol and glutathione (cosubstrates of the reaction) and L-cysteine (a primary reaction substrate). It is suggested that this change in the spectrum is due to the action of SH-compounds on the enzyme conformation before the beginning of the enzymatic reaction or on its initial stages.", "contents": "[Some physical and chemical properties of serinesulfhydrase from chicken liver]. An improved procedure of purification of serinesulfhydrase from chicken liver is described. Preparations of enzyme (700-fold purification with the yield of 40 per cent from total activity) have been obtained homogeneous on polyacrylamide gel electrophoresis. Molecular weight of serinesulfhydrase is 90.000; 1 mole of enzyme contains 2 moles of pyridoxalphosphate and consists apparently of 2 subunits. Amino acid composition of the enzyme is studied. Absorption spectrum of serinesulfhydrase has a maximum at 430 nm what is characteristic of numerous pyridoxal-P enzymes. The position of this maximum does not depend on pH (within its range 6--10) and the presence of  L-serine, a primary enzyme substrate. An essential change in the absorption spectrum of enzyme was observed in the presence of some thiol compound--DL-homocysteine, beta-mercaptoethanol and glutathione (cosubstrates of the reaction) and L-cysteine (a primary reaction substrate). It is suggested that this change in the spectrum is due to the action of SH-compounds on the enzyme conformation before the beginning of the enzymatic reaction or on its initial stages."}
{"id": "PMID:1110", "title": "[Specificity of extracellular alkaline RNAase from Penicillium chrysogenum 152A].", "content": "Specificity of chromatographically homogenous extracellular alkaline RNAase from Pen. crysogenum 152A on RNA, synthetic polynucleotides, dinucleosidemonophosphates and nucleoside-2',3'-cyclophosphates is studied. The enzyme is found to release from RNA guanosine-3'-monophosphate and guanosine-2',3'-cyclophosphate only. Guanylic acid is a 3'-terminal nucleotide of oligonucleotides of different length. The enzyme readily hydrolyses poly-I and practically do not splits poly-G. GpN is demonstrated to be a good substrate for the RNase, while G greater than p hydrolyses with a low rate. The RNAase catalyses the synthesis of GpC (47.7 per cent yield) and GpU (38.8 per cent yield). Thus, the RNAase from Pen. chrysogenum 152A is considered to be guanyl-RNAase.", "contents": "[Specificity of extracellular alkaline RNAase from Penicillium chrysogenum 152A]. Specificity of chromatographically homogenous extracellular alkaline RNAase from Pen. crysogenum 152A on RNA, synthetic polynucleotides, dinucleosidemonophosphates and nucleoside-2',3'-cyclophosphates is studied. The enzyme is found to release from RNA guanosine-3'-monophosphate and guanosine-2',3'-cyclophosphate only. Guanylic acid is a 3'-terminal nucleotide of oligonucleotides of different length. The enzyme readily hydrolyses poly-I and practically do not splits poly-G. GpN is demonstrated to be a good substrate for the RNase, while G greater than p hydrolyses with a low rate. The RNAase catalyses the synthesis of GpC (47.7 per cent yield) and GpU (38.8 per cent yield). Thus, the RNAase from Pen. chrysogenum 152A is considered to be guanyl-RNAase."}
{"id": "PMID:1111", "title": "[Intermediate plateaux in kinetics of the reaction catalyzed by biodegradative L-threonine dehydratase from Escherichia coli].", "content": "It has been shown that for the reaction catalyzed by \"biodegradative\" L-threonine dehydratase from E. coli strains K-12 and 980 in 0.5 M phosphate-carbonate buffer, pH 8.4 and pH 9.5, the plots of initial reaction rate (v) versus the initial substrate concentration ([S]0 are characterized by several inflection points, i. e. an intermediate plateau. The plot of v versus the allosteric activator (AMP) concentration have very complicated shapes: there are several inflection points, and also the maximum at L-threonine concentration equal to 3-10(2) and 5-10(-2) M. High AMP concentrations inhibit the enzyme at high substrate concentrations. The reduced glutathion dose not influence the enzyme and does not alter the activating effect of AMP. On the basis of the data obtained it is proposed that the substrate and AMP shift the equilibrium between multiple oligomeric enzyme forms differing in catalytic activity and kinetic manifestations of allosteric interactions between the active and allosteric AMP-binding sites towards polymerization. Thus, the functioning the enzyme under study is discussed in the frames of the model of dissociating regulatory enzymes with multiple intermediate oligomeric forms.", "contents": "[Intermediate plateaux in kinetics of the reaction catalyzed by biodegradative L-threonine dehydratase from Escherichia coli]. It has been shown that for the reaction catalyzed by \"biodegradative\" L-threonine dehydratase from E. coli strains K-12 and 980 in 0.5 M phosphate-carbonate buffer, pH 8.4 and pH 9.5, the plots of initial reaction rate (v) versus the initial substrate concentration ([S]0 are characterized by several inflection points, i. e. an intermediate plateau. The plot of v versus the allosteric activator (AMP) concentration have very complicated shapes: there are several inflection points, and also the maximum at L-threonine concentration equal to 3-10(2) and 5-10(-2) M. High AMP concentrations inhibit the enzyme at high substrate concentrations. The reduced glutathion dose not influence the enzyme and does not alter the activating effect of AMP. On the basis of the data obtained it is proposed that the substrate and AMP shift the equilibrium between multiple oligomeric enzyme forms differing in catalytic activity and kinetic manifestations of allosteric interactions between the active and allosteric AMP-binding sites towards polymerization. Thus, the functioning the enzyme under study is discussed in the frames of the model of dissociating regulatory enzymes with multiple intermediate oligomeric forms."}
{"id": "PMID:1113", "title": "[Multiple forms of rabbit muscle phosphofructokinase revealed by means of specific elution].", "content": "The modified procedure for rabbit skeletal muscle phosphofructokinase (PFK) purification is worked out utioizing the method of specific elution from DEAE-cellulose in 0.1 M tris-EDTA-phosphate pH 8.0 with 10 mM citrate. By the latter procedure PFK can be resolved into fractions A, B and C which are eluted specifically, with 0.3 M buffer and with 1.5 M NaCl respectively. Rechromatography of each fraction reveals their interconvertibility. The preparations are characterized by disc electrophoresis and velocity sedimentation. The results of formalinization experiments demonstrate that high concentrations of formaldehyde dissociate PFK u to the 5.3 S component. The presence of the 19.3 S component in the formalinized preparations evidences against the possibility that the middle component, presented at the schlieren patterns of PFK at pH 8.0, is and artifact of superposition. Complex profiles of protein distribution observed in different transport experiments are discussed from the point of view of slow equilibrium of oligomers and conformers characteristic to PFK over the pH range from 6 to 9.", "contents": "[Multiple forms of rabbit muscle phosphofructokinase revealed by means of specific elution]. The modified procedure for rabbit skeletal muscle phosphofructokinase (PFK) purification is worked out utioizing the method of specific elution from DEAE-cellulose in 0.1 M tris-EDTA-phosphate pH 8.0 with 10 mM citrate. By the latter procedure PFK can be resolved into fractions A, B and C which are eluted specifically, with 0.3 M buffer and with 1.5 M NaCl respectively. Rechromatography of each fraction reveals their interconvertibility. The preparations are characterized by disc electrophoresis and velocity sedimentation. The results of formalinization experiments demonstrate that high concentrations of formaldehyde dissociate PFK u to the 5.3 S component. The presence of the 19.3 S component in the formalinized preparations evidences against the possibility that the middle component, presented at the schlieren patterns of PFK at pH 8.0, is and artifact of superposition. Complex profiles of protein distribution observed in different transport experiments are discussed from the point of view of slow equilibrium of oligomers and conformers characteristic to PFK over the pH range from 6 to 9."}
{"id": "PMID:1112", "title": "[Isoenzymes of phosphorylase from skeletal muscles of cyclostomata and raw-boned fish].", "content": "Separation and partial purification of isoenzymes of phosphorylase B from skeletal muscles of lamprey (Lampetra) and carp (Cyprinus carpio) was carried out. Isoenzyme I was adsorbed on DEAE cellulose and eluted by KCl; isoenzyme II was not adsorbed on DEAE cellulose. A number of kinetic characteristics of phosphorylase of the coldblooded were determined, e. g. Km values for glucose-1-phosphate, glycogen and AMP; Ki for glucose-6-phosphate; stability towards denaturation (heating and effect of urea) and pH optimum. It was observed that in the course of evolution of vertebrates the Km values for substrates and allosteric activator (AMP), as well as the inhibition by glucose-6-phosphate showed a decrease. Isoenzymes I and II of phosphorylase B were found non-identical with respect to some molecular characteristics, in carp the differences being far more pronounced than in lamprey.", "contents": "[Isoenzymes of phosphorylase from skeletal muscles of cyclostomata and raw-boned fish]. Separation and partial purification of isoenzymes of phosphorylase B from skeletal muscles of lamprey (Lampetra) and carp (Cyprinus carpio) was carried out. Isoenzyme I was adsorbed on DEAE cellulose and eluted by KCl; isoenzyme II was not adsorbed on DEAE cellulose. A number of kinetic characteristics of phosphorylase of the coldblooded were determined, e. g. Km values for glucose-1-phosphate, glycogen and AMP; Ki for glucose-6-phosphate; stability towards denaturation (heating and effect of urea) and pH optimum. It was observed that in the course of evolution of vertebrates the Km values for substrates and allosteric activator (AMP), as well as the inhibition by glucose-6-phosphate showed a decrease. Isoenzymes I and II of phosphorylase B were found non-identical with respect to some molecular characteristics, in carp the differences being far more pronounced than in lamprey."}
{"id": "PMID:1115", "title": "[Activity of polynucleotide phosphorylase in ribosomal fraction of rat liver].", "content": "A method of isolating polynucleotidephosphorylase (PNPase) containing polyribosome fraction from rat liver is described. PNPase is found to be bind to RNA in polyribosomes with weak electrostatic bonds which are easily broken down in a weak alkaline medium with ionic strength more than 0.1 beta-22P-labelled ADP, GDP, UDP and CDP are found among the products of endogenous RNA degradation in the fraction of total polyribosomes in the presence of 32P-orthophosphate. A considerable change in the base composition of PNP-degraded RNA is observed at different incubation times of total polyribosomes with 32P-orthophosphate: G+C//A+U ratio increased from 2.3 to 3.1, and purines/pyrimidines ratio-from 0.47 to 1.06 with the increase of the incubation time. Specific activity of PNP in ribosome fractions obtained under ultracentrifugation of total polyribosomes in succrose density gradient (0.3-1.0 M) increased in the direction from the fraction of heavy polysomes to trimers and dimers and then dropped at the region of monomers (80 S particles). The data obtained give no possibility to determine the type of PNP-bound RNA in polyribomes of rat liver.", "contents": "[Activity of polynucleotide phosphorylase in ribosomal fraction of rat liver]. A method of isolating polynucleotidephosphorylase (PNPase) containing polyribosome fraction from rat liver is described. PNPase is found to be bind to RNA in polyribosomes with weak electrostatic bonds which are easily broken down in a weak alkaline medium with ionic strength more than 0.1 beta-22P-labelled ADP, GDP, UDP and CDP are found among the products of endogenous RNA degradation in the fraction of total polyribosomes in the presence of 32P-orthophosphate. A considerable change in the base composition of PNP-degraded RNA is observed at different incubation times of total polyribosomes with 32P-orthophosphate: G+C//A+U ratio increased from 2.3 to 3.1, and purines/pyrimidines ratio-from 0.47 to 1.06 with the increase of the incubation time. Specific activity of PNP in ribosome fractions obtained under ultracentrifugation of total polyribosomes in succrose density gradient (0.3-1.0 M) increased in the direction from the fraction of heavy polysomes to trimers and dimers and then dropped at the region of monomers (80 S particles). The data obtained give no possibility to determine the type of PNP-bound RNA in polyribomes of rat liver."}
{"id": "PMID:1116", "title": "[The effect of oxidazable substrates and ATP on the sensitivity of certain energy-dependent functions submitochondrial particles to phospholipases A, C and D].", "content": "The effect of NADH, succinate and ATP on the sensitivity of a number of energy-dependent functions of submitochondrial particles ot phospholipases A, C and D has been studied. It has been shown that in the conditions of oxidation of NADH and succinate by oxygen and also of ATP hydrolysis, the decrease in the phosphorylating activity of the particles under the action of phospholipases C and D accelerates. No such acceleration has been observed with phospholipase A. For other two functions, i. e. reverse electron transfer (ATP-dependent NAD+ reduction by succinate) and ATP-dependent transhydrogenase reaction the results proved to be different. Oxidizable substrates and ATP promoted the maintenance of these functions in the presence of phospholipase A, but did not retard their suppression by phospholipases C and D. The effects of NADH, succinate and ATP on the sensitivity  of different energy-dependent functions of submitochondrial particles to phospholipases A, C and D could be removed by the uncoupling agent carbonyl cyanide-m-chlorophenyl hydrazone. The conclusion is made that the effects revealed are associated with an increase in the sensitivity of coupling sites II PAND/OR III to phospholipases C and D and with a decrease in the sensitivity of sites I and IV to phospholipase A on energization of submitochondrial particles.", "contents": "[The effect of oxidazable substrates and ATP on the sensitivity of certain energy-dependent functions submitochondrial particles to phospholipases A, C and D]. The effect of NADH, succinate and ATP on the sensitivity of a number of energy-dependent functions of submitochondrial particles ot phospholipases A, C and D has been studied. It has been shown that in the conditions of oxidation of NADH and succinate by oxygen and also of ATP hydrolysis, the decrease in the phosphorylating activity of the particles under the action of phospholipases C and D accelerates. No such acceleration has been observed with phospholipase A. For other two functions, i. e. reverse electron transfer (ATP-dependent NAD+ reduction by succinate) and ATP-dependent transhydrogenase reaction the results proved to be different. Oxidizable substrates and ATP promoted the maintenance of these functions in the presence of phospholipase A, but did not retard their suppression by phospholipases C and D. The effects of NADH, succinate and ATP on the sensitivity  of different energy-dependent functions of submitochondrial particles to phospholipases A, C and D could be removed by the uncoupling agent carbonyl cyanide-m-chlorophenyl hydrazone. The conclusion is made that the effects revealed are associated with an increase in the sensitivity of coupling sites II PAND/OR III to phospholipases C and D and with a decrease in the sensitivity of sites I and IV to phospholipase A on energization of submitochondrial particles."}
{"id": "PMID:1114", "title": "[Flourescent properties of histidine decarboxylase from Micrococcus sp. n].", "content": "A dependency of fluorescence parameters of histidinedecarboxylase (HDC) from Micrococcuc sp. n. on pH values is studied. Native HDS has a short-waved maximum position (325 nm) and a small half-width of the fluorescence spectrum (48nm). The change in the quantum yield of the enzyme fluorescence was parallel with the change of the enzymatic activity. Triptophane residues of native HDC are located at hydrophobic region of the enzyme globula. The dependency of HDC flourescence parameters on pH values in 8 M urea was similar to that of free triptophane. A comparative study of fluorescences parameters of HDC and its inhibitory complexes with methyl ester of histidine (MEH), hydroxylamine and p-chloromercuriumbensoate is carried out. The effect of HDC interacting with inhibitors on fluorescence parameters of the enzyme is discussed. No differences were found in infra-red spectra of HDC and its inhibitory complex with MEH.", "contents": "[Flourescent properties of histidine decarboxylase from Micrococcus sp. n]. A dependency of fluorescence parameters of histidinedecarboxylase (HDC) from Micrococcuc sp. n. on pH values is studied. Native HDS has a short-waved maximum position (325 nm) and a small half-width of the fluorescence spectrum (48nm). The change in the quantum yield of the enzyme fluorescence was parallel with the change of the enzymatic activity. Triptophane residues of native HDC are located at hydrophobic region of the enzyme globula. The dependency of HDC flourescence parameters on pH values in 8 M urea was similar to that of free triptophane. A comparative study of fluorescences parameters of HDC and its inhibitory complexes with methyl ester of histidine (MEH), hydroxylamine and p-chloromercuriumbensoate is carried out. The effect of HDC interacting with inhibitors on fluorescence parameters of the enzyme is discussed. No differences were found in infra-red spectra of HDC and its inhibitory complex with MEH."}
{"id": "PMID:1120", "title": "A model for the origin of stable protocells in a primitive alkaline ocean.", "content": "When a mixture of the eighteen proteinous amino acids are suitably heated in the dry state with seawater salts, a copolyamino acid results. One fraction of this polymer is found, through isoelectric focusing, to consist of a mixture of acidic and basic proteinoids, each of sharply limited heterogeneity. When one fraction of the seawater proteinoid is dissolved in hot water, and the solution is cooled, proteinoid microspheres result. These have properties in common with simpler types, but also stable at pH values to 9, in common with microspheres prepared by mixing acidic and basic proteinoids. These processes thus constitute a simple model for the origin of a protocell stable in a primitive alkaline ocean.", "contents": "A model for the origin of stable protocells in a primitive alkaline ocean. When a mixture of the eighteen proteinous amino acids are suitably heated in the dry state with seawater salts, a copolyamino acid results. One fraction of this polymer is found, through isoelectric focusing, to consist of a mixture of acidic and basic proteinoids, each of sharply limited heterogeneity. When one fraction of the seawater proteinoid is dissolved in hot water, and the solution is cooled, proteinoid microspheres result. These have properties in common with simpler types, but also stable at pH values to 9, in common with microspheres prepared by mixing acidic and basic proteinoids. These processes thus constitute a simple model for the origin of a protocell stable in a primitive alkaline ocean."}
{"id": "PMID:1121", "title": "Hypothesis on the role of liganded states of proteins in energy transducing systems.", "content": "In energy transducing systems the direction of energy transfer is proposed to be maintained by the synchronized turnovers of the conformational change of one protein coupling up to affect another. Catalysis by those systems implies, therefore, that under new space restrictions the groups of the transducing enzyme increase and decrease reactivity between themselves, with activatory and/or inhibitory ligands (H+, H2O, metals, etc.) and with the electron shells of the reactant molecules. The exergonic reaction-dependent turnover of the forms of the enzyme within the transition complexes would be maintained, therefore, under asymmetric phase angles of conformational-dependent reactivity that would effectively restrict the microscopic reversibility of transducing systems. Some well known reactions, such as hemoglobins Bohr effect, can be used to illustrate that microscopic (molecular) interactions subject to thermodynamic equilibria laws may similarly paricipate as driving forces in energy transducing sytems. This would allow the thermodynamic description of the role of proton translocation as that of a modificatory force of the structural parameters of proteins. Similarly, the relationship between the liganded states of hemoglobin and its change in conformation has been used to develop an illustrative model relating changes in oxido-reduction of electron carriers to induced-fit effects leading to a sequence of ATPase forms in transition complexes which become stabilized as high energy intermediates under the constraints imposed by the membrane of energy transducing organelles.", "contents": "Hypothesis on the role of liganded states of proteins in energy transducing systems. In energy transducing systems the direction of energy transfer is proposed to be maintained by the synchronized turnovers of the conformational change of one protein coupling up to affect another. Catalysis by those systems implies, therefore, that under new space restrictions the groups of the transducing enzyme increase and decrease reactivity between themselves, with activatory and/or inhibitory ligands (H+, H2O, metals, etc.) and with the electron shells of the reactant molecules. The exergonic reaction-dependent turnover of the forms of the enzyme within the transition complexes would be maintained, therefore, under asymmetric phase angles of conformational-dependent reactivity that would effectively restrict the microscopic reversibility of transducing systems. Some well known reactions, such as hemoglobins Bohr effect, can be used to illustrate that microscopic (molecular) interactions subject to thermodynamic equilibria laws may similarly paricipate as driving forces in energy transducing sytems. This would allow the thermodynamic description of the role of proton translocation as that of a modificatory force of the structural parameters of proteins. Similarly, the relationship between the liganded states of hemoglobin and its change in conformation has been used to develop an illustrative model relating changes in oxido-reduction of electron carriers to induced-fit effects leading to a sequence of ATPase forms in transition complexes which become stabilized as high energy intermediates under the constraints imposed by the membrane of energy transducing organelles."}
{"id": "PMID:1122", "title": "Some properties of a protease (subtilisin BPN') immobilized to porous glass.", "content": "Subtilisin BPN' was immobilized to porous glass via isothiocyanate coupling. The pH optimum of the enzyme was shifted to the alkaline side on binding. This effect was more pronounced with ethyl lactate than with N-tosyl arginine methyl ester (TAME). Presumably, the shift is a reflection of the negative charge on the surface of the glass. The Michaelis constant and Vmax of soluble subtilisin BPN' with TAME were two and one orders of magnitude, respectively, lower than with ethyl lactate. Vmax, calculated per g of active enzyme, with TAME as the substrate was not affected by immobilization, while Vmax with ethyl lactate decreased greater than tenfold. The apparent KM decreased on immobilization with ethyl lactate as substrate and increased with TAME. Results are explained in terms of diffusional resistance and a possible attraction of ethyl lactate to the glass surface. Active site titration indicated that about 25% of the immobilized enzyme was active.", "contents": "Some properties of a protease (subtilisin BPN') immobilized to porous glass. Subtilisin BPN' was immobilized to porous glass via isothiocyanate coupling. The pH optimum of the enzyme was shifted to the alkaline side on binding. This effect was more pronounced with ethyl lactate than with N-tosyl arginine methyl ester (TAME). Presumably, the shift is a reflection of the negative charge on the surface of the glass. The Michaelis constant and Vmax of soluble subtilisin BPN' with TAME were two and one orders of magnitude, respectively, lower than with ethyl lactate. Vmax, calculated per g of active enzyme, with TAME as the substrate was not affected by immobilization, while Vmax with ethyl lactate decreased greater than tenfold. The apparent KM decreased on immobilization with ethyl lactate as substrate and increased with TAME. Results are explained in terms of diffusional resistance and a possible attraction of ethyl lactate to the glass surface. Active site titration indicated that about 25% of the immobilized enzyme was active."}
{"id": "PMID:1123", "title": "Profiles for pH, temperature, and dissolved O2 levels in enzyme production: monitoring in small-scale fermentors.", "content": "The profiles thus established may be utilized for investigations of an organism's relationship to its microenvironment including metabolic shifts and pathways. Areas of maximum respiratory activity, enzyme production, enzyme degradation, and attainment of the stationary phase are quite evident; however, duration and magnitude of the various phenomena may change with nutrient, temperature, and aeration efficiency. Practical application of this simplified method would include: a) determination of environmental conditions existing during maximum growth or enzyme synthesis and application of these conditions to feedback control; b) estimation of requirements for pH, oxygen, and heat removal capacities needed for scale-up; c) specific points during the fermentation at which samples should be analyzed to yield maximum information on depletion of nutrients and its effects on microbial activity.", "contents": "Profiles for pH, temperature, and dissolved O2 levels in enzyme production: monitoring in small-scale fermentors. The profiles thus established may be utilized for investigations of an organism's relationship to its microenvironment including metabolic shifts and pathways. Areas of maximum respiratory activity, enzyme production, enzyme degradation, and attainment of the stationary phase are quite evident; however, duration and magnitude of the various phenomena may change with nutrient, temperature, and aeration efficiency. Practical application of this simplified method would include: a) determination of environmental conditions existing during maximum growth or enzyme synthesis and application of these conditions to feedback control; b) estimation of requirements for pH, oxygen, and heat removal capacities needed for scale-up; c) specific points during the fermentation at which samples should be analyzed to yield maximum information on depletion of nutrients and its effects on microbial activity."}
{"id": "PMID:1126", "title": "The specificity of heterophil antibodies in patients and healthy donors with no or minimal signs of infectious mononucleosis.", "content": "Over several years sera were collected from 14 heterophil-positive students or patients who did not fulfill minimal hematologic criteria for infectious mononucleosis (I.M.) The specificity of these heterophil reactions for I.M. was investigated by determining antibodies to Epstein-Barr virus-determined antigens, i.e., to viral capsid antigens (VCA), early antigens (EA), and EBV-associated nuclear antigens (EBNA). On the basis of detectable anti-EA and/or the early absence and late emergence of anti-EBNA, four of these 14 individuals showed evidence of a current or very recent primary Epstein-Barr virus infection. The other ten patients showed antibody patterns indicative of Epstein-Barr virus infections in the past, and no firm conclusions could be drawn with regard to the specificity of their heterophil reactions. It was assumed, however, that some represented atypical clinical forms of EBV infection and that timing of specimen collection was a factor in explaining the paucity of Downey cells. In three patients, the absorbed heterophil-positive reactions persisted with little change in titer for at least 22 mo and thus might represent false-positive tests.", "contents": "The specificity of heterophil antibodies in patients and healthy donors with no or minimal signs of infectious mononucleosis. Over several years sera were collected from 14 heterophil-positive students or patients who did not fulfill minimal hematologic criteria for infectious mononucleosis (I.M.) The specificity of these heterophil reactions for I.M. was investigated by determining antibodies to Epstein-Barr virus-determined antigens, i.e., to viral capsid antigens (VCA), early antigens (EA), and EBV-associated nuclear antigens (EBNA). On the basis of detectable anti-EA and/or the early absence and late emergence of anti-EBNA, four of these 14 individuals showed evidence of a current or very recent primary Epstein-Barr virus infection. The other ten patients showed antibody patterns indicative of Epstein-Barr virus infections in the past, and no firm conclusions could be drawn with regard to the specificity of their heterophil reactions. It was assumed, however, that some represented atypical clinical forms of EBV infection and that timing of specimen collection was a factor in explaining the paucity of Downey cells. In three patients, the absorbed heterophil-positive reactions persisted with little change in titer for at least 22 mo and thus might represent false-positive tests."}
{"id": "PMID:1127", "title": "Bone marrow transplantation for aplastic anaemia from a HL-A and MLC-identical unrelated donor.", "content": "Bone-marrow transplantation (BMT) from an unrelated, HL-A-phenotype-identical, MLC-negative donor was performed in a 31 year old woman with severe longlasting aplastic anemia. In vitro assays failed to demonstrate humoral or cellular sensitization of the recipient against donor-type antigens. Following conditioning with cyclophosphamide, prompt but only transient engraftment of the transplant occurred accompanied by signs of mild graft-versus-host-disease (GVHD) of the liver. The results of a second bone marrow transplantation from the same donor cannot be evaluated due to early death of the recipient. It is concluded that bone marrow from unrelated, HL-A and MLC-identical donors may engraft without severe GVHD. Rejection of the graft in our patient may have been related to greater antigenic differences that can be expected to exist between HL-A and MLC-identical unrelated individuals than between HL-A and MLC-identical siblings. However, insufficient preparative immunosuppression with cyclophosphamide due to severe hepatic hemosiderosis appears equally likely as the cause of graft rejection. The possibly increased risk of graft rejection or severe GVHD should not preclude the use of unrelated HL-A and MLC-identical marrow donors, when histocompatible sibling donors are not available; but more potent immunosuppressive regimens than the cyclophosphamide protocol may be necessary to ensure permanent engraftment.", "contents": "Bone marrow transplantation for aplastic anaemia from a HL-A and MLC-identical unrelated donor. Bone-marrow transplantation (BMT) from an unrelated, HL-A-phenotype-identical, MLC-negative donor was performed in a 31 year old woman with severe longlasting aplastic anemia. In vitro assays failed to demonstrate humoral or cellular sensitization of the recipient against donor-type antigens. Following conditioning with cyclophosphamide, prompt but only transient engraftment of the transplant occurred accompanied by signs of mild graft-versus-host-disease (GVHD) of the liver. The results of a second bone marrow transplantation from the same donor cannot be evaluated due to early death of the recipient. It is concluded that bone marrow from unrelated, HL-A and MLC-identical donors may engraft without severe GVHD. Rejection of the graft in our patient may have been related to greater antigenic differences that can be expected to exist between HL-A and MLC-identical unrelated individuals than between HL-A and MLC-identical siblings. However, insufficient preparative immunosuppression with cyclophosphamide due to severe hepatic hemosiderosis appears equally likely as the cause of graft rejection. The possibly increased risk of graft rejection or severe GVHD should not preclude the use of unrelated HL-A and MLC-identical marrow donors, when histocompatible sibling donors are not available; but more potent immunosuppressive regimens than the cyclophosphamide protocol may be necessary to ensure permanent engraftment."}
{"id": "PMID:1132", "title": "Evidence for noradrenaline and adrenaline as sympathetic transmitters in the chicken.", "content": "1 The concentrations of noradrenaline and adrenaline in various organs, arterial plasma and venous outflow from isolated hearts of adult chickens have been determined. 2 The relative adrenaline concentrations (percentage of the sum of noradrenaline and adrenaline) in the heart (33%), spleen (16%) and brain (26%) were higher than those found in mammalian organs. Chemical sympathectomy by pretreatment with 6-hydroxydopamine caused a decrease of the noradrenaline and adrenaline concentrations in the heart to 20 and 23% and in the spleen to 16 and 29%, respectively. 3 Stimulation of the right sympathetic nerves, infusion of tyramine or infusion of a modified Tyrode solution containing 108mM K+ and 44 mM Na+ caused an output of both noradrenaline and adrenaline into the perfusate of isolated hearts. The relative adrenaline concentration in the perfusate (20-28%) was not significantly different from the relative adrenaline concentration remaining in these hearts (19-22%). In the individual experiments, the noradrenaline: adrenaline ratios of the stimulation perfusates were positively correlated with the ratios found in the hearts. 4 The effects of noradrenaline and adrenaline on cardiac rate and tension development were studied in spontaneously beating right atria and electrically driven left atria, respectively. In addition, the arterial pressure rise in response to noradrenaline or adrenaline was;measured in chickens. It was found that the cardio-vaseart rate, cardiac tension development and arterial blood pressure, was not significantly different from that of adrenaline. 5 It is concluded that, in the chicken heart and spleen, both noradrenaline and adrenaline act as sympathetic neutrotransmitters.", "contents": "Evidence for noradrenaline and adrenaline as sympathetic transmitters in the chicken. 1 The concentrations of noradrenaline and adrenaline in various organs, arterial plasma and venous outflow from isolated hearts of adult chickens have been determined. 2 The relative adrenaline concentrations (percentage of the sum of noradrenaline and adrenaline) in the heart (33%), spleen (16%) and brain (26%) were higher than those found in mammalian organs. Chemical sympathectomy by pretreatment with 6-hydroxydopamine caused a decrease of the noradrenaline and adrenaline concentrations in the heart to 20 and 23% and in the spleen to 16 and 29%, respectively. 3 Stimulation of the right sympathetic nerves, infusion of tyramine or infusion of a modified Tyrode solution containing 108mM K+ and 44 mM Na+ caused an output of both noradrenaline and adrenaline into the perfusate of isolated hearts. The relative adrenaline concentration in the perfusate (20-28%) was not significantly different from the relative adrenaline concentration remaining in these hearts (19-22%). In the individual experiments, the noradrenaline: adrenaline ratios of the stimulation perfusates were positively correlated with the ratios found in the hearts. 4 The effects of noradrenaline and adrenaline on cardiac rate and tension development were studied in spontaneously beating right atria and electrically driven left atria, respectively. In addition, the arterial pressure rise in response to noradrenaline or adrenaline was;measured in chickens. It was found that the cardio-vaseart rate, cardiac tension development and arterial blood pressure, was not significantly different from that of adrenaline. 5 It is concluded that, in the chicken heart and spleen, both noradrenaline and adrenaline act as sympathetic neutrotransmitters."}
{"id": "PMID:1133", "title": "Antiarrhythmic, haemodynamic and metabolic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride in greyhounds following acute coronary artery ligation.", "content": "1  The antiarrhythmic, haemodynamic and metabolic effects of a new amino steroid, ORG6001, have been investigated in experimental acute myocardial infarction in anaesthetized greyhounds. 2 ORG6001 administered either intravenously (2-10 mg/kg) or orally (50 mg/kg) significantly reduced the incidence of ventricular ectopic beats in the first 30 min after ligation of the left anterior descending coronary artery. 3 In dogs pretreated with ORG6001, metabolic changes indicative of myocardial ischaemia (lactate production and potassium efflux) were less marked than those occurring in control animals. 4 Antiarrhythmic doses of ORG6001 caused only minimal transient haemodynamic effects. 5 These results suggest that ORG6001 may possess distinct advantages over presently-used antiarrhythmic drugs in the prevention and treatment of the early arrhythmias which occur after myocardial infarction.", "contents": "Antiarrhythmic, haemodynamic and metabolic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride in greyhounds following acute coronary artery ligation. 1  The antiarrhythmic, haemodynamic and metabolic effects of a new amino steroid, ORG6001, have been investigated in experimental acute myocardial infarction in anaesthetized greyhounds. 2 ORG6001 administered either intravenously (2-10 mg/kg) or orally (50 mg/kg) significantly reduced the incidence of ventricular ectopic beats in the first 30 min after ligation of the left anterior descending coronary artery. 3 In dogs pretreated with ORG6001, metabolic changes indicative of myocardial ischaemia (lactate production and potassium efflux) were less marked than those occurring in control animals. 4 Antiarrhythmic doses of ORG6001 caused only minimal transient haemodynamic effects. 5 These results suggest that ORG6001 may possess distinct advantages over presently-used antiarrhythmic drugs in the prevention and treatment of the early arrhythmias which occur after myocardial infarction."}
{"id": "PMID:1134", "title": "The use of radioactive microspheres to compare the effects of hydralazine, guanethidine and SK & F 24260 on the redistribution of cardiac output in anaesthetized rabbits.", "content": "1 The use of radioactive microspheres is described for the measurement of cardiac output in anaesthetized rabbits and its redistribution after the administration of drugs which lower blood pressure. 2 Hydralazine increased peripheral vascular conductance by 123%. The vascular beds in which it had most effect were those of the carcass (mainly muscle) and the kidneys. 3 SK&F 24260, (1,4 dihydro-2, 6-dimethyl-4(2-trifluoremethylpheny)-3,5,-pyridinedicarboxylic acid diethyl ester), had similar vasocilator actions. Its effect in the carcass contributed relatively more to the increase of total peripheral conductance. It also caused a remarkable degree of cerebral vasodilatation. 4 Guanethidine had a relatively small effect on total peripheral conductance and lowered blood pressure mainly by reducing stroke volume and cardiac output.", "contents": "The use of radioactive microspheres to compare the effects of hydralazine, guanethidine and SK & F 24260 on the redistribution of cardiac output in anaesthetized rabbits. 1 The use of radioactive microspheres is described for the measurement of cardiac output in anaesthetized rabbits and its redistribution after the administration of drugs which lower blood pressure. 2 Hydralazine increased peripheral vascular conductance by 123%. The vascular beds in which it had most effect were those of the carcass (mainly muscle) and the kidneys. 3 SK&F 24260, (1,4 dihydro-2, 6-dimethyl-4(2-trifluoremethylpheny)-3,5,-pyridinedicarboxylic acid diethyl ester), had similar vasocilator actions. Its effect in the carcass contributed relatively more to the increase of total peripheral conductance. It also caused a remarkable degree of cerebral vasodilatation. 4 Guanethidine had a relatively small effect on total peripheral conductance and lowered blood pressure mainly by reducing stroke volume and cardiac output."}
{"id": "PMID:1135", "title": "Impact of psychosocial factors on the conduct of combined drug and psychotherapy research.", "content": "The effect of attitudes of therapists, patients and researchers on the conduct and outcome of combined drug and psychotherapy research was examined in a brief crisis-oriented psychotherapy clinic. Seventy-seven consecutive patients were given one of two anti-anxiety drugs or a placebo in conjunction with the typical psychoanalytically-oriented treatment used in the clinic. The therapists' attitudes favouring psychotherapy over drug therapy (and psychotherapy research) were clearly conveyed to the patients. Indicative of this are the following: (a) 82 per cent of the patients dropped out of drug taking, although a similar percentage remained in treatment; (b) only a third of the patients perceived it as being important to their therapists that they should take medication; (c) 87 per cent of the patients were rated as improved; and 75 per cent of patients completing forms considered that most or all of their improvement was attributable to talking. The research team, made up of members of the same department who therefore had similar values as the therapists, diligently collected outcome data, but ignored its responsibility to enforce drug-relation portions of the protocol. Overall, patients remained in therapy, improved and participated in completing forms, so that only the research goals of combined therapy were thwarted, while traditional clinic service and training goals proceeded as usual.", "contents": "Impact of psychosocial factors on the conduct of combined drug and psychotherapy research. The effect of attitudes of therapists, patients and researchers on the conduct and outcome of combined drug and psychotherapy research was examined in a brief crisis-oriented psychotherapy clinic. Seventy-seven consecutive patients were given one of two anti-anxiety drugs or a placebo in conjunction with the typical psychoanalytically-oriented treatment used in the clinic. The therapists' attitudes favouring psychotherapy over drug therapy (and psychotherapy research) were clearly conveyed to the patients. Indicative of this are the following: (a) 82 per cent of the patients dropped out of drug taking, although a similar percentage remained in treatment; (b) only a third of the patients perceived it as being important to their therapists that they should take medication; (c) 87 per cent of the patients were rated as improved; and 75 per cent of patients completing forms considered that most or all of their improvement was attributable to talking. The research team, made up of members of the same department who therefore had similar values as the therapists, diligently collected outcome data, but ignored its responsibility to enforce drug-relation portions of the protocol. Overall, patients remained in therapy, improved and participated in completing forms, so that only the research goals of combined therapy were thwarted, while traditional clinic service and training goals proceeded as usual."}
{"id": "PMID:1140", "title": "Neurochemical studies in a mouse teratoma with neuroepithelial differentiation. Presence of cyclic AMP, serotonin and enzymes of the serotonergic, adrenergic and cholinergic systems.", "content": "A transplantable mouse testicular teratoma (OTT 6050) which displays a spectrum of neuroepithelial differentiation was evaluated biochemically for concentrations of cyclic AMP (cAMP), serotonin (5-HT), and enzymes involved in the metabolism of the biogenic amines and acetylcholine. These values were compared between teratomas with neuroepithelial differentiation as the major or minor component and brains of neonatal and adult mice of related strains. cAMP, 5-HT, tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were present. In addition, enzymes of the adrenergic system, i.e. tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and of the cholinergic system, i.e. choline acetyltransferase and acetylcholinesterase, were studied. Biochemical differences in tumor groups probably reflected variations in the proportion of neuroepithelial components: trends suggested an increase of cAMP and an increased activity of TPH, AADC, TH and DBH in tumors with increased proportions of neuroepithelial cells. These findings indicate that the neuroepithelial component of the mouse teratoma may serve as a model for the study of neuronal differentiation in primitive neuroepithelial neoplasms.", "contents": "Neurochemical studies in a mouse teratoma with neuroepithelial differentiation. Presence of cyclic AMP, serotonin and enzymes of the serotonergic, adrenergic and cholinergic systems. A transplantable mouse testicular teratoma (OTT 6050) which displays a spectrum of neuroepithelial differentiation was evaluated biochemically for concentrations of cyclic AMP (cAMP), serotonin (5-HT), and enzymes involved in the metabolism of the biogenic amines and acetylcholine. These values were compared between teratomas with neuroepithelial differentiation as the major or minor component and brains of neonatal and adult mice of related strains. cAMP, 5-HT, tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were present. In addition, enzymes of the adrenergic system, i.e. tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and of the cholinergic system, i.e. choline acetyltransferase and acetylcholinesterase, were studied. Biochemical differences in tumor groups probably reflected variations in the proportion of neuroepithelial components: trends suggested an increase of cAMP and an increased activity of TPH, AADC, TH and DBH in tumors with increased proportions of neuroepithelial cells. These findings indicate that the neuroepithelial component of the mouse teratoma may serve as a model for the study of neuronal differentiation in primitive neuroepithelial neoplasms."}
{"id": "PMID:1141", "title": "Trans-synaptic regulation of the development of end organ innervation by sympathetic neurons.", "content": "To examine the regulation of development of end organ innervation the superior cervical ganglion (SCG), and two of its target organs, the iris and pineal gland, were studied using biochemical and histofluorescent approaches. During postnatal ontogeny the activity of tyrosine hydroxylase (T-OH), which is localized to adrenergic neurons, increased 50-fold in iris, and 34-fold in pineal nerve terminals of the rat. These increases paralleled the in vitro rise in iris [3H]norepinephrine ([3H]NE) uptake, a measure of the presence of functional nerve terminal membrane. These biochemical indices of end organ innervation correlated well with developmental increases in density of innervation, adrenergic ground plexus ramification and nerve fiber fluorescence intensity as determined by fluorescence microscopy. Unilateral transection of the presynaptic cholinergic nerves innervating the SCG in 2-3-day-old rats prevented the normal development of end organ innervation: T-OH activity, [3H]NE uptake, innervation density, plexus ramification and fluorescence intensity failed to develop normally in irides innervated by decentralized ganglia. It is concluded that trans-synaptic factors regulate the maturation of adrenergic nerve terminals, and the development of end organ innervation by SCG.", "contents": "Trans-synaptic regulation of the development of end organ innervation by sympathetic neurons. To examine the regulation of development of end organ innervation the superior cervical ganglion (SCG), and two of its target organs, the iris and pineal gland, were studied using biochemical and histofluorescent approaches. During postnatal ontogeny the activity of tyrosine hydroxylase (T-OH), which is localized to adrenergic neurons, increased 50-fold in iris, and 34-fold in pineal nerve terminals of the rat. These increases paralleled the in vitro rise in iris [3H]norepinephrine ([3H]NE) uptake, a measure of the presence of functional nerve terminal membrane. These biochemical indices of end organ innervation correlated well with developmental increases in density of innervation, adrenergic ground plexus ramification and nerve fiber fluorescence intensity as determined by fluorescence microscopy. Unilateral transection of the presynaptic cholinergic nerves innervating the SCG in 2-3-day-old rats prevented the normal development of end organ innervation: T-OH activity, [3H]NE uptake, innervation density, plexus ramification and fluorescence intensity failed to develop normally in irides innervated by decentralized ganglia. It is concluded that trans-synaptic factors regulate the maturation of adrenergic nerve terminals, and the development of end organ innervation by SCG."}
{"id": "PMID:1142", "title": "Mechanism of action of Mg2+ and Zn2+ on rat placental alkaline phosphatase. I. Studies on the soluble Zn2+ and Mg2+ alkaline phosphatases.", "content": "Rat placental alkaline phosphatase (EC 3.1.3.1), a dimer of 135,000 daltons, is strongly activated by Mg2+. However, Zn2+ has to be present on the apoenzyme to obtain this activation. Mg2+ alone is unable to reconstitute functional active sites. Excess Zn2+ which competes for the Mg2+ site leads to a phosphatase with little catalytic activity at alkaline pH but with normal active sites at acidic pH as shown by covalent incorporation of ortho-[32P]phosphate. Two enzyme species with identical functional active sites have been reconstituted that only differ by the presence of Zn2+ or Mg2+ at the effector site. A mechanism is presented by which alkaline phosphatase activity of rat placenta would be controlled by a molecular process involving the interaction of Mg2+ and Zn2+ with the dimeric enzyme molecule.", "contents": "Mechanism of action of Mg2+ and Zn2+ on rat placental alkaline phosphatase. I. Studies on the soluble Zn2+ and Mg2+ alkaline phosphatases. Rat placental alkaline phosphatase (EC 3.1.3.1), a dimer of 135,000 daltons, is strongly activated by Mg2+. However, Zn2+ has to be present on the apoenzyme to obtain this activation. Mg2+ alone is unable to reconstitute functional active sites. Excess Zn2+ which competes for the Mg2+ site leads to a phosphatase with little catalytic activity at alkaline pH but with normal active sites at acidic pH as shown by covalent incorporation of ortho-[32P]phosphate. Two enzyme species with identical functional active sites have been reconstituted that only differ by the presence of Zn2+ or Mg2+ at the effector site. A mechanism is presented by which alkaline phosphatase activity of rat placenta would be controlled by a molecular process involving the interaction of Mg2+ and Zn2+ with the dimeric enzyme molecule."}
{"id": "PMID:1143", "title": "Porcine chymotrypsin A-pi, a more acidic chymotrypsin.", "content": "A kinetic study of procine chymotrypsin A-pi revealed two characteristic properties of this type of chymotrypsin: 1. Porcine chymotrypsin A-pi, like bovine chymotrypsin B-pi does not bind proflavin, which is a competitive inhibitor of bovine trypsin and chymotrypsin A-alpha. 2. The pH profiles of the steady-state parameters show the two usual important pK's. The basic one, pK2 = 9.6, affects both Km and kcat/Km and probably controls the binding conformation of chymotrypsin. The acidic one, pK1 = 5.7, affects kcat and kcat/Km and plays a role in the catalytic process. The value of pK1 is unusually low.", "contents": "Porcine chymotrypsin A-pi, a more acidic chymotrypsin. A kinetic study of procine chymotrypsin A-pi revealed two characteristic properties of this type of chymotrypsin: 1. Porcine chymotrypsin A-pi, like bovine chymotrypsin B-pi does not bind proflavin, which is a competitive inhibitor of bovine trypsin and chymotrypsin A-alpha. 2. The pH profiles of the steady-state parameters show the two usual important pK's. The basic one, pK2 = 9.6, affects both Km and kcat/Km and probably controls the binding conformation of chymotrypsin. The acidic one, pK1 = 5.7, affects kcat and kcat/Km and plays a role in the catalytic process. The value of pK1 is unusually low."}
{"id": "PMID:1144", "title": "Properties of a free and a solubilized form of bound alpha,alpha-trehalase purified from honey bee thorax.", "content": "The free and bound forms of alpha,alpha-trehalase (EC 3.2.1.28) of the honey bee thorax were separated and the bound enzyme was solubilized by raising the pH to 8.0 for 10 h. Both enzymes were purified. They were homogeneous as determined by several electrophoretic criteria. It was found that the two enzymes had very similar Km's (each about 0.89 mM), Vm's (53.2 and 54.3 U/mg for free and solubilized, respectively), inhibition characteristics, specificities (both only hydrolyzed alpha,alpha-trehalose), pH maxima (each had maxima at about 3.5 and 6.5), molecular weights (65,000), isoelectric points (5.1), reactivities to sulfhydryl reagents, electrophoretic mobilities, activation energies (about 12.8 kcal/mol), and similar stabilities to heat, pH, and urea. Some significant differences between the two enzymes were, however, found: the solubilized alpha,alpha-trehalase floated at 70% saturation of ammonium sulfate while the free alpha,alpha-trehalase did not; the solubilized alpha,alpha-trehalase did not dissociate into subunits as readily as did the free one; and the solubilized alpha,alpha-trehalase was found to bind more readily to a hydrophobic grouping than the free enzyme. In addition to these comparisons, three new findings relating to thorax alpha,alpha-trehalases are reported. (1) Thorax alpha,alpha-trehalases are strongly inhibited by beta-glucosides (Ki values of about 8 x 10(-4) M); (2) under certain conditions thorax alpha,alpha-trehalases from honey bees dissociated into subunits of one-half the normal molecular weight; (3) honey bee thorax alpha,alpha-trehalases have unusual biphasic pH activity profiles.", "contents": "Properties of a free and a solubilized form of bound alpha,alpha-trehalase purified from honey bee thorax. The free and bound forms of alpha,alpha-trehalase (EC 3.2.1.28) of the honey bee thorax were separated and the bound enzyme was solubilized by raising the pH to 8.0 for 10 h. Both enzymes were purified. They were homogeneous as determined by several electrophoretic criteria. It was found that the two enzymes had very similar Km's (each about 0.89 mM), Vm's (53.2 and 54.3 U/mg for free and solubilized, respectively), inhibition characteristics, specificities (both only hydrolyzed alpha,alpha-trehalose), pH maxima (each had maxima at about 3.5 and 6.5), molecular weights (65,000), isoelectric points (5.1), reactivities to sulfhydryl reagents, electrophoretic mobilities, activation energies (about 12.8 kcal/mol), and similar stabilities to heat, pH, and urea. Some significant differences between the two enzymes were, however, found: the solubilized alpha,alpha-trehalase floated at 70% saturation of ammonium sulfate while the free alpha,alpha-trehalase did not; the solubilized alpha,alpha-trehalase did not dissociate into subunits as readily as did the free one; and the solubilized alpha,alpha-trehalase was found to bind more readily to a hydrophobic grouping than the free enzyme. In addition to these comparisons, three new findings relating to thorax alpha,alpha-trehalases are reported. (1) Thorax alpha,alpha-trehalases are strongly inhibited by beta-glucosides (Ki values of about 8 x 10(-4) M); (2) under certain conditions thorax alpha,alpha-trehalases from honey bees dissociated into subunits of one-half the normal molecular weight; (3) honey bee thorax alpha,alpha-trehalases have unusual biphasic pH activity profiles."}
{"id": "PMID:1145", "title": "Immunotherapy for cancer: an overview.", "content": "Immunotherapy of cancer is of interest to oncologists because it is specifically directed to cancer cells, sparing normal cells. While it is ineffective in most patients, especially those with widespread metastatic disease, it occasionally produces good results. Each of the available methods has inherent problems and, recently, attempts have been made to overcome some of these. There is a strong case for small-scale experimental trials in highly selected groups of patients who are intensively investigated for their immunologic status in relation to their tumour. Despite the lack of success in general, immunotherapy still appears to have a future as an adjunct to existing therapy in order to control as much as to cure residual tumour.", "contents": "Immunotherapy for cancer: an overview. Immunotherapy of cancer is of interest to oncologists because it is specifically directed to cancer cells, sparing normal cells. While it is ineffective in most patients, especially those with widespread metastatic disease, it occasionally produces good results. Each of the available methods has inherent problems and, recently, attempts have been made to overcome some of these. There is a strong case for small-scale experimental trials in highly selected groups of patients who are intensively investigated for their immunologic status in relation to their tumour. Despite the lack of success in general, immunotherapy still appears to have a future as an adjunct to existing therapy in order to control as much as to cure residual tumour."}
{"id": "PMID:1147", "title": "L-[alphaS, 5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501): a new amino acid antibiotic with the properties of an antagonist of L-glutamine.", "content": "L-[alphaS,5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501), an antibiotic elaborated by Streptomyces sviceus, has been shown to be a powerful inhibitor of many mammalian and bacterial reactions involving the transfer of nitrogen from the gamma-carboxamide of L-glutamine. Thus, the utilization of L-glutamine for the synthesis of carbamyl phosphate, L-asparagine, guanosine-5'-monophosphate, cytidine-5'-triphosphate, N-formylglycinamidine ribonucleotide, NAD, glucosamine-6-phosphate, and anthranilic acid is strongly or totally inhibited by a concentration of NSC-163501 of 1 X 10(-3) M. L-Glutamate synthetase of Escherichia coli is only modestly inhibited and 5-phosphoribosylamine synthesis in fetal rat liver is comparatively refractory to inhibition. NSC-163501 treatment of L1210 cells growing in a low L-glutamine culture medium produced arrest in G or early S phase. Of the amino acids tested, only L-glutamine antagonized such growth inhibition.", "contents": "L-[alphaS, 5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501): a new amino acid antibiotic with the properties of an antagonist of L-glutamine. L-[alphaS,5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501), an antibiotic elaborated by Streptomyces sviceus, has been shown to be a powerful inhibitor of many mammalian and bacterial reactions involving the transfer of nitrogen from the gamma-carboxamide of L-glutamine. Thus, the utilization of L-glutamine for the synthesis of carbamyl phosphate, L-asparagine, guanosine-5'-monophosphate, cytidine-5'-triphosphate, N-formylglycinamidine ribonucleotide, NAD, glucosamine-6-phosphate, and anthranilic acid is strongly or totally inhibited by a concentration of NSC-163501 of 1 X 10(-3) M. L-Glutamate synthetase of Escherichia coli is only modestly inhibited and 5-phosphoribosylamine synthesis in fetal rat liver is comparatively refractory to inhibition. NSC-163501 treatment of L1210 cells growing in a low L-glutamine culture medium produced arrest in G or early S phase. Of the amino acids tested, only L-glutamine antagonized such growth inhibition."}
{"id": "PMID:1148", "title": "Antitumor and immunosuppressive activities of lankacidin-group antibiotics: structure-activity relationships.", "content": "The antitumor and immunosuppressive activities of the lankacidin-group antibiotics were studied in mice. Seventeen of 29 newly prepared lankacidin-group antibiotics, including 14-derivatives of lankacidin C, lankacidinol, isolankacidinol, and lankacidinol 14-acetate, possessed considerable antitumor activity against ascites 6C3HED/OG lymphosarcoma. Comparative studies on the antitumor activity of lankacidin C and eight of its derivatives against L1210 leukemia and solid 6C3HED/OG lymphosarcoma demonstrated that replacement of the hydroxyl group at position 8 or 14 of lankacidin C by an acyloxy group potentiated antitumor activity. However, these modifications of lankacidin C resulted in reduction of the immunosuppressive activity.", "contents": "Antitumor and immunosuppressive activities of lankacidin-group antibiotics: structure-activity relationships. The antitumor and immunosuppressive activities of the lankacidin-group antibiotics were studied in mice. Seventeen of 29 newly prepared lankacidin-group antibiotics, including 14-derivatives of lankacidin C, lankacidinol, isolankacidinol, and lankacidinol 14-acetate, possessed considerable antitumor activity against ascites 6C3HED/OG lymphosarcoma. Comparative studies on the antitumor activity of lankacidin C and eight of its derivatives against L1210 leukemia and solid 6C3HED/OG lymphosarcoma demonstrated that replacement of the hydroxyl group at position 8 or 14 of lankacidin C by an acyloxy group potentiated antitumor activity. However, these modifications of lankacidin C resulted in reduction of the immunosuppressive activity."}
{"id": "PMID:1155", "title": "Evidence for a physiological role of renal sympathetic nerves in adrenergic stimulation of renin release in the rat.", "content": "Previous studies on renin release by an in vitro system of rat kidney slices, which is devoid of hemodynamic influences, have provided evidence that renin release is stimulated by a beta-adrenergic mechanism. We used this system to study effects of tyramine (an indirectly acting amine capable of displacing endogenous catecholmines from sympathetic nerve endings) on renin release. Tyramine (10(-3)M) in the presence of a monoamine oxidase inhibitor (pheniprazine, 10(-5)M) and a phosphodiesterase inhibitor (theophylline, 10(-3)M) significantly (P less than 0.01) stimulated renin release when values were compared to control observations for media containing only the inhibitors. Tyramine-induced stimulation of renin release was blocked by the beta-blocking agent, propranolol (2 X 10(-4) M), and the neural uptake blocking agent, cocaine (10(-5) M), but not by the alpha-antagonist, phentolamine (9 X 10(-4) M). These observations demonstrate a potential role for the sympathetic innervation of the juxtaglomerular apparatus on renin release.", "contents": "Evidence for a physiological role of renal sympathetic nerves in adrenergic stimulation of renin release in the rat. Previous studies on renin release by an in vitro system of rat kidney slices, which is devoid of hemodynamic influences, have provided evidence that renin release is stimulated by a beta-adrenergic mechanism. We used this system to study effects of tyramine (an indirectly acting amine capable of displacing endogenous catecholmines from sympathetic nerve endings) on renin release. Tyramine (10(-3)M) in the presence of a monoamine oxidase inhibitor (pheniprazine, 10(-5)M) and a phosphodiesterase inhibitor (theophylline, 10(-3)M) significantly (P less than 0.01) stimulated renin release when values were compared to control observations for media containing only the inhibitors. Tyramine-induced stimulation of renin release was blocked by the beta-blocking agent, propranolol (2 X 10(-4) M), and the neural uptake blocking agent, cocaine (10(-5) M), but not by the alpha-antagonist, phentolamine (9 X 10(-4) M). These observations demonstrate a potential role for the sympathetic innervation of the juxtaglomerular apparatus on renin release."}
{"id": "PMID:1156", "title": "Effects of storage in the cold on activity of gamma-glutamyltransferase in serum.", "content": "Sera from patients with hepatobiliary disorders were selected to represent a wide range of activity of gamma-glutamyltransferase (EC 2.3.2.2). Samples were stored at 4 degrees C and periodically tested for as long as nine weeks, others at -6 degrees C for as long as 40 weeks. The frozen-stored samples were thawed and then frozen again after each testing. The activity of the enzyme was essentially unchanged under both conditions of storage. These results are consistent with comments in the literature on the enzyme's stability.", "contents": "Effects of storage in the cold on activity of gamma-glutamyltransferase in serum. Sera from patients with hepatobiliary disorders were selected to represent a wide range of activity of gamma-glutamyltransferase (EC 2.3.2.2). Samples were stored at 4 degrees C and periodically tested for as long as nine weeks, others at -6 degrees C for as long as 40 weeks. The frozen-stored samples were thawed and then frozen again after each testing. The activity of the enzyme was essentially unchanged under both conditions of storage. These results are consistent with comments in the literature on the enzyme's stability."}
{"id": "PMID:1158", "title": "Quantitative fractionation of alkaline phosphatase isoenzymes according to their thermostability.", "content": "Continuous monitoring of heat denaturation of a mixture of alkaline phosphatase isoenzymes at 60 degrees C and pH 7.5 permits the simultaneous direct identification and quantitation of three isoenzymes: the placental isoenzyme, the L-phenylalanine-sensitive intestinal isoenzyme, and the liver isoenzyme (hepatocytic). The isoenzyme that is principally of bone origin cannot be identified as such without the help of other diagnostic aids and the patient's medical history. All human tissues contain alkaline phosphatase, many organs more than one of the isoenzymes. Liver alkaline phosphatase, which constitutes 40-50% of normal serum alkaline phosphatase activity, was measured in the serum of persons with various liver diseases. Its activity exceeded normal in all types of liver disease; in 80% of cases this increase was accompanied by increased gamma-glutamyl-transferase activity, but the quantitative correlationship (r = 0.54) was not as good as expected if both enzymes come from the same source and are indices of liver dieases. Liver alkaline phosphatase activity increases in the blood early in liver disease, before most liver tests show abnormalities. The other major isoenzyme of normal serum probably represents a mixture of isoenzymes from bone and reticulo-endothelial and vascular tissues, which all contain the same \"very heat-labile\" alkaline phosphatase. Cord blood and children's sera contain mostly this very heat-labile isoenzyme.", "contents": "Quantitative fractionation of alkaline phosphatase isoenzymes according to their thermostability. Continuous monitoring of heat denaturation of a mixture of alkaline phosphatase isoenzymes at 60 degrees C and pH 7.5 permits the simultaneous direct identification and quantitation of three isoenzymes: the placental isoenzyme, the L-phenylalanine-sensitive intestinal isoenzyme, and the liver isoenzyme (hepatocytic). The isoenzyme that is principally of bone origin cannot be identified as such without the help of other diagnostic aids and the patient's medical history. All human tissues contain alkaline phosphatase, many organs more than one of the isoenzymes. Liver alkaline phosphatase, which constitutes 40-50% of normal serum alkaline phosphatase activity, was measured in the serum of persons with various liver diseases. Its activity exceeded normal in all types of liver disease; in 80% of cases this increase was accompanied by increased gamma-glutamyl-transferase activity, but the quantitative correlationship (r = 0.54) was not as good as expected if both enzymes come from the same source and are indices of liver dieases. Liver alkaline phosphatase activity increases in the blood early in liver disease, before most liver tests show abnormalities. The other major isoenzyme of normal serum probably represents a mixture of isoenzymes from bone and reticulo-endothelial and vascular tissues, which all contain the same \"very heat-labile\" alkaline phosphatase. Cord blood and children's sera contain mostly this very heat-labile isoenzyme."}
{"id": "PMID:1159", "title": "Spectrophotometric end-point method for assay of serum cystyl-aminopeptidase in pregnancy.", "content": "An optimized end-point method that requires little sophisticated equipment is described for estimating serum cystyl-aminopeptidase during pregnancy. S-Benzyl-L-cysteine-4-nitroanilide is used as the substrate.", "contents": "Spectrophotometric end-point method for assay of serum cystyl-aminopeptidase in pregnancy. An optimized end-point method that requires little sophisticated equipment is described for estimating serum cystyl-aminopeptidase during pregnancy. S-Benzyl-L-cysteine-4-nitroanilide is used as the substrate."}
{"id": "PMID:1160", "title": "Improved separation of creatine kinase cardiac isoenzyme in serum by batch fractionation.", "content": "I describe a simple, single-tube batch fractionation procedure for separating MM and MB isoenzymes of creatine kinase on a macroporous strong anion exchanger (AG MP-1, Bio-Rad Laboratories). The isoenzymes can be separated in less than 3 min, with a resulting dilution of the serum with no more than an equal volume of buffer. Without sample concentration or spectrofluorometric measurement, the procedure detects 4 U of MB isoenzyme per liter. Sensitivity is limited by the sensitivity and precision of the method of measurement. The CV for the fractionation can be held to less than 4.0% at 65 U of MB per liter. Current fractionation methods are compared to the proposed procedure. With use of a discrete analyzer (Du Pont aca) the mean MB activity in a population free of heart disease was 3.2 +/- 3.0 U/liter (range, 0 to 8 U/liter). The kinetics and stability of isolated isoenzymes are reported, indicating that advisability of storing or pre-incubating samples with mercaptoethanol.", "contents": "Improved separation of creatine kinase cardiac isoenzyme in serum by batch fractionation. I describe a simple, single-tube batch fractionation procedure for separating MM and MB isoenzymes of creatine kinase on a macroporous strong anion exchanger (AG MP-1, Bio-Rad Laboratories). The isoenzymes can be separated in less than 3 min, with a resulting dilution of the serum with no more than an equal volume of buffer. Without sample concentration or spectrofluorometric measurement, the procedure detects 4 U of MB isoenzyme per liter. Sensitivity is limited by the sensitivity and precision of the method of measurement. The CV for the fractionation can be held to less than 4.0% at 65 U of MB per liter. Current fractionation methods are compared to the proposed procedure. With use of a discrete analyzer (Du Pont aca) the mean MB activity in a population free of heart disease was 3.2 +/- 3.0 U/liter (range, 0 to 8 U/liter). The kinetics and stability of isolated isoenzymes are reported, indicating that advisability of storing or pre-incubating samples with mercaptoethanol."}
{"id": "PMID:1161", "title": "The dependence of tryptamine excretion on urinary pH.", "content": "It is demonstrated that urinary tryptamine decreases significantly with increasing urinary pH. This effect becomes important at a urinary pH of 6.5 and over.", "contents": "The dependence of tryptamine excretion on urinary pH. It is demonstrated that urinary tryptamine decreases significantly with increasing urinary pH. This effect becomes important at a urinary pH of 6.5 and over."}
{"id": "PMID:1162", "title": "A stabilising factor for gamma-glutamyl transpeptidase in urine.", "content": "Urinary gamma-glutamyl transpeptidase (gamma-GT) has been found to be stable when stored at room temperature and 4 degrees C. Activity is lost rapidly when urine is frozen but prior dialysis will prevent this loss. Urea is the major factor responsible for the loss of activity; albumin is protective at concentrations of 6 g/l or more. A factor of 10 000-30 000 molecular weight which will prevent the loss of urinary gamma-GT activity on freezing has been found in serum and urine; it has high potency in serum and in urine from patients with chronic renal failure, but only low potency in normal urine. Its nature is unknown but it is heat stable.", "contents": "A stabilising factor for gamma-glutamyl transpeptidase in urine. Urinary gamma-glutamyl transpeptidase (gamma-GT) has been found to be stable when stored at room temperature and 4 degrees C. Activity is lost rapidly when urine is frozen but prior dialysis will prevent this loss. Urea is the major factor responsible for the loss of activity; albumin is protective at concentrations of 6 g/l or more. A factor of 10 000-30 000 molecular weight which will prevent the loss of urinary gamma-GT activity on freezing has been found in serum and urine; it has high potency in serum and in urine from patients with chronic renal failure, but only low potency in normal urine. Its nature is unknown but it is heat stable."}
{"id": "PMID:1163", "title": "Properties of beta-glucuronidase activity in human synovial fluid.", "content": "The purpose of the present study was to evaluate the properties of beta-glucuronidase (EC 3.2.1.31) in human synovial fluid. It was shown to have a pH requirement of 5.0 and a KM value of about 8.0 - 10(-3) M using phenolphthalein beta-glucuronide as the substrate. At low substrate concentration an endogenous inhibitor is demonstrable. The inhibition is of the competitive type and is removed by proteolytic digestion of synovial fluid, whereas hyaluronidase digestion and addition either of Triton X-100 or of various salts to the assay mixture, are ineffective. The possibility that the inhibitor is a protein from serum is discussed.", "contents": "Properties of beta-glucuronidase activity in human synovial fluid. The purpose of the present study was to evaluate the properties of beta-glucuronidase (EC 3.2.1.31) in human synovial fluid. It was shown to have a pH requirement of 5.0 and a KM value of about 8.0 - 10(-3) M using phenolphthalein beta-glucuronide as the substrate. At low substrate concentration an endogenous inhibitor is demonstrable. The inhibition is of the competitive type and is removed by proteolytic digestion of synovial fluid, whereas hyaluronidase digestion and addition either of Triton X-100 or of various salts to the assay mixture, are ineffective. The possibility that the inhibitor is a protein from serum is discussed."}
{"id": "PMID:1164", "title": "Glucose-phosphate isomerase deficiency due to a new variant (GP I Barcelona) and to a silent gene: biochemical, immunological and genetic studies.", "content": "A 12-year-old girl of Spanish origin was found to be double heterozygote for a deficient GP I variant (GP I Barcelona) and for a silent GP I gene. The mother was heterozygote for GP I Barcelona and the father was heterozygote for the silent gene. GP I Barcelona was a fast variant (116%) with an increased isoelectric point (9.55), lability to heat and to urea, and shift of the pH curve towards the acidic pH. The other kinetic characteristics were normal. The ratio of enzymatic activity to immunological reactivity was normal in erythrocytes and white blood cells of the father and the mother but decreased to 75% of normal in blood cells of the daughter. The genetic and molecular mechanisms of GP I deficiency of this patient are discussed.", "contents": "Glucose-phosphate isomerase deficiency due to a new variant (GP I Barcelona) and to a silent gene: biochemical, immunological and genetic studies. A 12-year-old girl of Spanish origin was found to be double heterozygote for a deficient GP I variant (GP I Barcelona) and for a silent GP I gene. The mother was heterozygote for GP I Barcelona and the father was heterozygote for the silent gene. GP I Barcelona was a fast variant (116%) with an increased isoelectric point (9.55), lability to heat and to urea, and shift of the pH curve towards the acidic pH. The other kinetic characteristics were normal. The ratio of enzymatic activity to immunological reactivity was normal in erythrocytes and white blood cells of the father and the mother but decreased to 75% of normal in blood cells of the daughter. The genetic and molecular mechanisms of GP I deficiency of this patient are discussed."}
{"id": "PMID:1166", "title": "Rosette formation by mouse lymphocytes. IV. Fc and C3 receptors occurring together and separately on T cells and other leucocytes.", "content": "A method is described for detecting the simultaneous presence of Fc and C3 receptors on mouse spleen cells. A proportion of both T cells and non-T cells bear both receptors. Both T-cell and non-T-cell Fc receptors were blocked by aggregated mouse IgG2 to the same degree. C3, but not Fc, receptors were blocked by factors present in the serum of irradiated mice or mice undergoing graft-versus-host reaction. Thymocytes activated by injection into irradiated F1 hybrid mice, and thymocytes regenerating after irradiation and bone marrow injection, appeared to have increased Fc receptors. A general role for Fc and C3 receptors in T cell-B cell co-operation is suggested.", "contents": "Rosette formation by mouse lymphocytes. IV. Fc and C3 receptors occurring together and separately on T cells and other leucocytes. A method is described for detecting the simultaneous presence of Fc and C3 receptors on mouse spleen cells. A proportion of both T cells and non-T cells bear both receptors. Both T-cell and non-T-cell Fc receptors were blocked by aggregated mouse IgG2 to the same degree. C3, but not Fc, receptors were blocked by factors present in the serum of irradiated mice or mice undergoing graft-versus-host reaction. Thymocytes activated by injection into irradiated F1 hybrid mice, and thymocytes regenerating after irradiation and bone marrow injection, appeared to have increased Fc receptors. A general role for Fc and C3 receptors in T cell-B cell co-operation is suggested."}
{"id": "PMID:1168", "title": "Fluroxene toxicity induced by phenobarbital.", "content": "Because of reports of fluroxene toxicity in man, the effect of phenobarbital treatment on the toxicity and metabolism of fluroxene was studied in 9 rhesus monkeys. Six monkeys that were exposed to a mean calculated alveolar fluroxene concentration of 5.8% for 4-hr periods up to a total of 16 hr showed no evidence of toxicity. Two animals were sacrificed after a single 4-hr exposure to obtain control measures of fluroxene metabolites in tissues. Four monkeys that had previously survived received exposures to fluroxene and 3 monkeys that had no exposure to fluroxene died during fluroxene anesthesia after treatment with phenobarbital (mean time, 3 hr). Toxicity was manifested by arterial hypotension, pulmonary edema, and arterial hypoxemia. Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol. Concentrations of trifluoroethanol in mixed-expired gas, blood, and urine, and of total nonvolatile fluorine in blood, urine, and tissues of animals treated with phenobarbital were 2 to 10 times as in control animals. The results suggest that the rhesus monkey is a valuable model for the study of fluroxene pharmacology and that inclusion of an enzyme-inducing challenge in the evaluation of potential toxicity of other anesthetics seems warranted.", "contents": "Fluroxene toxicity induced by phenobarbital. Because of reports of fluroxene toxicity in man, the effect of phenobarbital treatment on the toxicity and metabolism of fluroxene was studied in 9 rhesus monkeys. Six monkeys that were exposed to a mean calculated alveolar fluroxene concentration of 5.8% for 4-hr periods up to a total of 16 hr showed no evidence of toxicity. Two animals were sacrificed after a single 4-hr exposure to obtain control measures of fluroxene metabolites in tissues. Four monkeys that had previously survived received exposures to fluroxene and 3 monkeys that had no exposure to fluroxene died during fluroxene anesthesia after treatment with phenobarbital (mean time, 3 hr). Toxicity was manifested by arterial hypotension, pulmonary edema, and arterial hypoxemia. Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol. Concentrations of trifluoroethanol in mixed-expired gas, blood, and urine, and of total nonvolatile fluorine in blood, urine, and tissues of animals treated with phenobarbital were 2 to 10 times as in control animals. The results suggest that the rhesus monkey is a valuable model for the study of fluroxene pharmacology and that inclusion of an enzyme-inducing challenge in the evaluation of potential toxicity of other anesthetics seems warranted."}
{"id": "PMID:1169", "title": "Plasma concentrations and the time-course of beta blockade due to propranolol.", "content": "The effectiveness of intravenously administered propranolol in antagonizing the chronotropic effect of isoproterenol and exercise has been investigated, and has been found at all times to be a predictable function of its plasma concentrations according to the classical drug-receptor theory for competitive antagonism. The data show further that the relationship between effectiveness and time depends on the way in which antagonism is measured. If the dose ratio to isoproterenol (DR) is measured, then (DR-1) declines with time in parallel with drug concentration. On the other hand, if propranolol's effects are measured as percentage reduction in a given response, then this declines linearly with time, even though plasma concentrations decline exponentially. This fact explains why confusion has in the past arisen concerning the relationship of the duration of beta blockade and pharmacokinetic half-life.", "contents": "Plasma concentrations and the time-course of beta blockade due to propranolol. The effectiveness of intravenously administered propranolol in antagonizing the chronotropic effect of isoproterenol and exercise has been investigated, and has been found at all times to be a predictable function of its plasma concentrations according to the classical drug-receptor theory for competitive antagonism. The data show further that the relationship between effectiveness and time depends on the way in which antagonism is measured. If the dose ratio to isoproterenol (DR) is measured, then (DR-1) declines with time in parallel with drug concentration. On the other hand, if propranolol's effects are measured as percentage reduction in a given response, then this declines linearly with time, even though plasma concentrations decline exponentially. This fact explains why confusion has in the past arisen concerning the relationship of the duration of beta blockade and pharmacokinetic half-life."}
{"id": "PMID:1170", "title": "Evaluation of lorazepam and pentobarbital as surgical premedicants.", "content": "Lorazepam, a new benzodiazepine, was compared with a standard surgical premedicant, pentobarbital. In a double-blind study in 128 patients, lorazepam, 2 and 4 mg, and pentobarbital, 50 and 100 mg, were given intravenously in a randomized sequence. Significant differences were noted; lorazepam was found to provide greater sedation, lack of recall, and greater antianxiety effect than pentobarbital. No significant adverse effects were noted following either drug. Vital signs remained stable.", "contents": "Evaluation of lorazepam and pentobarbital as surgical premedicants. Lorazepam, a new benzodiazepine, was compared with a standard surgical premedicant, pentobarbital. In a double-blind study in 128 patients, lorazepam, 2 and 4 mg, and pentobarbital, 50 and 100 mg, were given intravenously in a randomized sequence. Significant differences were noted; lorazepam was found to provide greater sedation, lack of recall, and greater antianxiety effect than pentobarbital. No significant adverse effects were noted following either drug. Vital signs remained stable."}
{"id": "PMID:1171", "title": "The renal elimination of procainamide.", "content": "The question of pH or flow dependence for the renal elimination of procainamide (PCA) was studied under 4 conditions in each of 4 subjects. Each subject received 500 mg of PCA intravenously at weekly intervals while in a state of (1) acid load (NH4Cl) and water deprivation, (2) acid load and water excess, (3) alkali load (NaHCO3) and water deprivation, and (4) alkali load and water excess. Plasma and urine were collected at frequent intervals for PCA and N-acetyl PCA (NAPA) analysis. Urine flow rates varied markedly between the water deprivation and water excess states (approximately 1.2 vs 5 ml/min, respectively), and urine pH varied markedly between the acid and alkali load states (pH = ca 5 vs 8, respectively). Despite this marked variation, there were no significant changes in PCA renal clearance or 24-hr PCA or NAPA excretion. If passive diffusion of PCA were taking place, such flow and pH changes would have caused marked changes in PCA clearance were the pH partition hypothesis true. We therefore conclude that passive diffusion is not an important mechanism in the renal elimination of PCA in man and that there must be tubular secretion. The implication for the clinical use of the drug is that dose adjustments need not be made in response to variations in urine flow and pH.", "contents": "The renal elimination of procainamide. The question of pH or flow dependence for the renal elimination of procainamide (PCA) was studied under 4 conditions in each of 4 subjects. Each subject received 500 mg of PCA intravenously at weekly intervals while in a state of (1) acid load (NH4Cl) and water deprivation, (2) acid load and water excess, (3) alkali load (NaHCO3) and water deprivation, and (4) alkali load and water excess. Plasma and urine were collected at frequent intervals for PCA and N-acetyl PCA (NAPA) analysis. Urine flow rates varied markedly between the water deprivation and water excess states (approximately 1.2 vs 5 ml/min, respectively), and urine pH varied markedly between the acid and alkali load states (pH = ca 5 vs 8, respectively). Despite this marked variation, there were no significant changes in PCA renal clearance or 24-hr PCA or NAPA excretion. If passive diffusion of PCA were taking place, such flow and pH changes would have caused marked changes in PCA clearance were the pH partition hypothesis true. We therefore conclude that passive diffusion is not an important mechanism in the renal elimination of PCA in man and that there must be tubular secretion. The implication for the clinical use of the drug is that dose adjustments need not be made in response to variations in urine flow and pH."}
{"id": "PMID:1172", "title": "Seasonal variations in the composition of urine in relation to calcium stone-formation.", "content": "1. A retrospective cross-sectional study was carried out on data derived from single 24 h urine collections from 246 male idiopathic calcium stone-formers. 2. The daily urine volume and pH and the exretions of calcium, oxalate, phosphate, creatinine and magnesium were related to the time of year when the urine was collected, and the saturation of urine with calcium oxalate and octocalcium phosphate calculated for each month. 3. There were significant seasonal variations in the urinary excretion of calcium and oxalate, each showing a maximum during the summer months and a minimum in the winter. There was no significant seasonal variation in urinary pH, volume, creatinine, phosphate or magnesium. 4. There was a significant increase in the saturation of urine with calcium oxalate and a trend towards higher saturation levels of octo-calcium phosphate in the summer. These changes were dependent only on the seasonal variation in urinary calcium and oxalate and not on urine volume. 5. A retrospective study of the seasonal incidence of stone episodes among these 246 stone-formers showed that the rate of stone passage per month was 50% higher in the summer than in the winter. There was no significant seasonal variation in the incidence of stones removed surgically.", "contents": "Seasonal variations in the composition of urine in relation to calcium stone-formation. 1. A retrospective cross-sectional study was carried out on data derived from single 24 h urine collections from 246 male idiopathic calcium stone-formers. 2. The daily urine volume and pH and the exretions of calcium, oxalate, phosphate, creatinine and magnesium were related to the time of year when the urine was collected, and the saturation of urine with calcium oxalate and octocalcium phosphate calculated for each month. 3. There were significant seasonal variations in the urinary excretion of calcium and oxalate, each showing a maximum during the summer months and a minimum in the winter. There was no significant seasonal variation in urinary pH, volume, creatinine, phosphate or magnesium. 4. There was a significant increase in the saturation of urine with calcium oxalate and a trend towards higher saturation levels of octo-calcium phosphate in the summer. These changes were dependent only on the seasonal variation in urinary calcium and oxalate and not on urine volume. 5. A retrospective study of the seasonal incidence of stone episodes among these 246 stone-formers showed that the rate of stone passage per month was 50% higher in the summer than in the winter. There was no significant seasonal variation in the incidence of stones removed surgically."}
{"id": "PMID:1207", "title": "Problems of the pathogenesis, clinics, and therapy of panarteritis of the aorta and its branches.", "content": "138 patients with panarteritis of the aorta and its branches were examined, and the clinical and morphological findings were compared. The disease is more widespread than has been assumed so far, and is more frequent in young women. Localization of the process in the abdominal aorta with involvement (stenosis) of renal arteries causes renovascular hypertension, which often has a malignant course, especially with an ambilateral affection of renal arteries. In the treatment, repetitive therapeutic courses with corticosteroids and heparin are of fundamental importance. With an isolated affection, especially in renovascular hypertension and disturbances of cerebral circulation, surgical treatment is also indicated.", "contents": "Problems of the pathogenesis, clinics, and therapy of panarteritis of the aorta and its branches. 138 patients with panarteritis of the aorta and its branches were examined, and the clinical and morphological findings were compared. The disease is more widespread than has been assumed so far, and is more frequent in young women. Localization of the process in the abdominal aorta with involvement (stenosis) of renal arteries causes renovascular hypertension, which often has a malignant course, especially with an ambilateral affection of renal arteries. In the treatment, repetitive therapeutic courses with corticosteroids and heparin are of fundamental importance. With an isolated affection, especially in renovascular hypertension and disturbances of cerebral circulation, surgical treatment is also indicated."}
{"id": "PMID:1213", "title": "Lorazepam and diazepam in the treatment of neurotic anxiety: a double-blind trial.", "content": "Fifty-eight neurotic patients with intense anxiety were treated with either lorazepam or diazepam in a double blind between-patients trial. Statistical analysis indicated that the two groups were homogeneous before treatment and that the results of treatment were similar for both drugs. According to the global rating of illness week after week, after four weeks of treatment more patients on lorazepam than on diazepam were normal or had mild illness (82.1% vs. 70.8%). In the investigators' judgment, 71.9% of the patients treated with lorazepam had an excellent or good response compared with 56.7+ of those treated with diazepam. The mean reduction in score on the Hamilton Anxiety Scale was 17.7 for lorazepam and 16.5 for diazepam. However, none of the above differences in results were statistically significant. The largest dose of lorazepam required in treatment was 6 mg, compared with 30 mg of diazepam. Two patients treated with lorazepam had side effects, against six with diazepam. Six patients in the diazepam group did not complete the trial, including three who discontinued because of side effects (rash, tremors, agitation); no patients in the lorazepam group dropped out.", "contents": "Lorazepam and diazepam in the treatment of neurotic anxiety: a double-blind trial. Fifty-eight neurotic patients with intense anxiety were treated with either lorazepam or diazepam in a double blind between-patients trial. Statistical analysis indicated that the two groups were homogeneous before treatment and that the results of treatment were similar for both drugs. According to the global rating of illness week after week, after four weeks of treatment more patients on lorazepam than on diazepam were normal or had mild illness (82.1% vs. 70.8%). In the investigators' judgment, 71.9% of the patients treated with lorazepam had an excellent or good response compared with 56.7+ of those treated with diazepam. The mean reduction in score on the Hamilton Anxiety Scale was 17.7 for lorazepam and 16.5 for diazepam. However, none of the above differences in results were statistically significant. The largest dose of lorazepam required in treatment was 6 mg, compared with 30 mg of diazepam. Two patients treated with lorazepam had side effects, against six with diazepam. Six patients in the diazepam group did not complete the trial, including three who discontinued because of side effects (rash, tremors, agitation); no patients in the lorazepam group dropped out."}
{"id": "PMID:1217", "title": "Identification and urinary excretion of p-chlorophenoxyacetamide, a metabolite of iproclozide, in humans.", "content": "The presence of p-chlorophenoxyacetamide was detected in the urine of man receiving iproclozide [1-(p-chlorophenoxyacetyl)-2-isopropylhydrazine]. This new metabolite was identified by combined gas-liquid chromatography-mass spectrometry and by comparison with the synthetic compound. An appropriate procedure for the extraction and quantitation of p-chlorophenoxyacetamide by gas-liquid chromatography on a 5% OV-225-packed column with the 2-butyl analog of iproclozide as an internal standard, has been developed. After 20- and 50-mg single dose oral administrations of iproclozide, 5.2 and 8.3% were slowly excreted in urine as p-chlorophenoxyacetamide within 30.5 and 36 hr. respectively. After 20-mg oral intakes by psychiatric patients, the 24-hr urinary excretion of p-chlorophenoxyacetamide amounted to about 2-4% of the iproclozide dose administered.", "contents": "Identification and urinary excretion of p-chlorophenoxyacetamide, a metabolite of iproclozide, in humans. The presence of p-chlorophenoxyacetamide was detected in the urine of man receiving iproclozide [1-(p-chlorophenoxyacetyl)-2-isopropylhydrazine]. This new metabolite was identified by combined gas-liquid chromatography-mass spectrometry and by comparison with the synthetic compound. An appropriate procedure for the extraction and quantitation of p-chlorophenoxyacetamide by gas-liquid chromatography on a 5% OV-225-packed column with the 2-butyl analog of iproclozide as an internal standard, has been developed. After 20- and 50-mg single dose oral administrations of iproclozide, 5.2 and 8.3% were slowly excreted in urine as p-chlorophenoxyacetamide within 30.5 and 36 hr. respectively. After 20-mg oral intakes by psychiatric patients, the 24-hr urinary excretion of p-chlorophenoxyacetamide amounted to about 2-4% of the iproclozide dose administered."}
{"id": "PMID:1218", "title": "Tissue metabolites of trifluorperazine, fluphenazine, prochlorperazine, and perphenazine. Kinetics in chronic treatment.", "content": "Repeated oral treatment of male rats with piperazine-substituted phenothiazine drugs in doses of 25 mg/kg or more daily led to an accumulation of metabolites containing an ethylenediamine group instead of the piperazine ring. These products of ring degradation with and without removal of the N-alkyl group were found, together with the parent drugs and their N-dealkylated metabolites, in liver, lung, kidney, and spleen, as well as in brain when high doses were administered. After termination of treatment, the ethylenediamine derivatives were eliminated more slowly than were their congeners containing the intact piperazine ring. Parallel observations were made in dogs given fluphenazine in daily doses of up to 40 mg/kg. Quantitative differences were observed in the relative amounts of mono- and disubstituted ethylenediamine metabolites accumulated in rat tissues during treatment with the various drugs; the proportion of the monosubstituted product formed by N-dealkylation and ring cleavage declined in the following order: perazine, prochlorperazine, trifluoperazine, fluphenazine, perphenazine. Condensation products of the ethylenediamine derivatives with formaldehyde were split in the extraction procedure used.", "contents": "Tissue metabolites of trifluorperazine, fluphenazine, prochlorperazine, and perphenazine. Kinetics in chronic treatment. Repeated oral treatment of male rats with piperazine-substituted phenothiazine drugs in doses of 25 mg/kg or more daily led to an accumulation of metabolites containing an ethylenediamine group instead of the piperazine ring. These products of ring degradation with and without removal of the N-alkyl group were found, together with the parent drugs and their N-dealkylated metabolites, in liver, lung, kidney, and spleen, as well as in brain when high doses were administered. After termination of treatment, the ethylenediamine derivatives were eliminated more slowly than were their congeners containing the intact piperazine ring. Parallel observations were made in dogs given fluphenazine in daily doses of up to 40 mg/kg. Quantitative differences were observed in the relative amounts of mono- and disubstituted ethylenediamine metabolites accumulated in rat tissues during treatment with the various drugs; the proportion of the monosubstituted product formed by N-dealkylation and ring cleavage declined in the following order: perazine, prochlorperazine, trifluoperazine, fluphenazine, perphenazine. Condensation products of the ethylenediamine derivatives with formaldehyde were split in the extraction procedure used."}
{"id": "PMID:1220", "title": "Physiological disposition and metabolism of 5-(2',4'-difluorophenyl)salicyclic acid, a new salicylate.", "content": "5-(2'4'-Difluorophenyl) [carboxy-14C]salicyclic acid (MK-647) was quickly and completely absorbed in rats, dogs, and man. Peak levels of plasma radioactivity occurred in 1-2 hr after oral administration. The dose was 10 mg/kg in rats and dogs, and 50 or 500 mg in man. Most of the drug in plasma was intact MK-647 which was extensively bound to plasma protein. In man the peak concentration following the 500-mg dose was approximately 10 times that after the lower dose, which suggests that absorption rates of both doses were similar. Elimination of drug from plasma was dose-dependent. The area under the curve for MK-647-14C in plasma was 18 times higher following the 500-mg dose than the 50-mg dose. Dogs given 10 mg/kg orally or intravenously excreted 44% of the dose in the urine and 42% in the feces in 72 hr. Rats given the same dose level by either route of administration excreted 80% in the urine and 11% in the feces. In man approximately 95% of a 50- or 500-mg oral dose was excreted in the urine and 3% in the feces, in 96 hr. MK-647 and two metabolites were present in the urine of three species. The ether and ester glucuronides were identified in human urine. The latter metabolite was also identified in rat and dog urine. The glycine conjugate of MK-647 was not observed in the urine of the three species. No interaction was observed between MK-647 and bishydroxycoumarin in the prothrombin time test nor with tolbutamide in the glucose tolerance test. A significant lowering of hexobarbital sleeping time was observed in female, but not male rats after four consecutive daily doses of MK-647. After repeated daily administration of MK-647 (12.5-100 mg/kg), the diurnal plasma level in dogs was not significantly altered, indicating that no saturation, induction, or inhibition of its own metabolism took place.", "contents": "Physiological disposition and metabolism of 5-(2',4'-difluorophenyl)salicyclic acid, a new salicylate. 5-(2'4'-Difluorophenyl) [carboxy-14C]salicyclic acid (MK-647) was quickly and completely absorbed in rats, dogs, and man. Peak levels of plasma radioactivity occurred in 1-2 hr after oral administration. The dose was 10 mg/kg in rats and dogs, and 50 or 500 mg in man. Most of the drug in plasma was intact MK-647 which was extensively bound to plasma protein. In man the peak concentration following the 500-mg dose was approximately 10 times that after the lower dose, which suggests that absorption rates of both doses were similar. Elimination of drug from plasma was dose-dependent. The area under the curve for MK-647-14C in plasma was 18 times higher following the 500-mg dose than the 50-mg dose. Dogs given 10 mg/kg orally or intravenously excreted 44% of the dose in the urine and 42% in the feces in 72 hr. Rats given the same dose level by either route of administration excreted 80% in the urine and 11% in the feces. In man approximately 95% of a 50- or 500-mg oral dose was excreted in the urine and 3% in the feces, in 96 hr. MK-647 and two metabolites were present in the urine of three species. The ether and ester glucuronides were identified in human urine. The latter metabolite was also identified in rat and dog urine. The glycine conjugate of MK-647 was not observed in the urine of the three species. No interaction was observed between MK-647 and bishydroxycoumarin in the prothrombin time test nor with tolbutamide in the glucose tolerance test. A significant lowering of hexobarbital sleeping time was observed in female, but not male rats after four consecutive daily doses of MK-647. After repeated daily administration of MK-647 (12.5-100 mg/kg), the diurnal plasma level in dogs was not significantly altered, indicating that no saturation, induction, or inhibition of its own metabolism took place."}
{"id": "PMID:1219", "title": "Comparative biotransformation of triflubazam in rats, dogs, and monkeys.", "content": "The biotransformation of 14C-triflubazam (ORF 8063; 1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepin-2-4-[3H,5H]-dione) was investigated in rats, dogs, and monkeys. Urinary metabolites, representing 65, 74, and 87%, respectively, of the total urinary radioactivity excreted by these three species, were isolated by preparative layer chromatography and characterized by various spectral techniques including gas chromatography/mass spectrometry, solid probe mass spectrometry, polarimetry, and infrared and nuclear magnetic resonance spectrometry. No parent drug was found in the urine of any species. Four metabolites were isolated from the rat including the 4'-hydroxyphenyl, dihydrodiol, and 3'-methoxy-4'hydroxy derivatives. N-demethylated metabolites were not isolated from rat urine. Five metabolites were isolated from dog urine, including 4-hydroxyphenyl, dihydrodiol, and catechol derivatives of triflubazam. Unlike the case of the rat, a catechol-O-methyl ether was not detected in dog urine. Six metabolites were isolated from monkey urine. The only major difference in metabolism in the monkey was the existence of both the dihydrodiol and N-desmethyldihydrodiol metabolites. No catechol-0-methyl ether was detected in monkey urine. Biotransformation through a common arene oxide intermediate can be proposed for these three animal species.", "contents": "Comparative biotransformation of triflubazam in rats, dogs, and monkeys. The biotransformation of 14C-triflubazam (ORF 8063; 1-methyl-5-phenyl-7-trifluoromethyl-1H-1,5-benzodiazepin-2-4-[3H,5H]-dione) was investigated in rats, dogs, and monkeys. Urinary metabolites, representing 65, 74, and 87%, respectively, of the total urinary radioactivity excreted by these three species, were isolated by preparative layer chromatography and characterized by various spectral techniques including gas chromatography/mass spectrometry, solid probe mass spectrometry, polarimetry, and infrared and nuclear magnetic resonance spectrometry. No parent drug was found in the urine of any species. Four metabolites were isolated from the rat including the 4'-hydroxyphenyl, dihydrodiol, and 3'-methoxy-4'hydroxy derivatives. N-demethylated metabolites were not isolated from rat urine. Five metabolites were isolated from dog urine, including 4-hydroxyphenyl, dihydrodiol, and catechol derivatives of triflubazam. Unlike the case of the rat, a catechol-O-methyl ether was not detected in dog urine. Six metabolites were isolated from monkey urine. The only major difference in metabolism in the monkey was the existence of both the dihydrodiol and N-desmethyldihydrodiol metabolites. No catechol-0-methyl ether was detected in monkey urine. Biotransformation through a common arene oxide intermediate can be proposed for these three animal species."}
{"id": "PMID:1222", "title": "N-hydroxyamobarbital: the second major metabolite of amobarbital in man.", "content": "After oral administration of 14C-labeled amobarbital to healthy subjects, most of the radioactivity was recovered in urine and only 4-5% in feces over a period of 6 days. No unchanged amobarbital was excreted. Two major metabolites were found and isolated. One was 3'-hydroxyamobarbital, which has been previously identified by Maynert. The second could be identified as N-hydroxyamobarbital on the basis of its spectral and chemical properties.", "contents": "N-hydroxyamobarbital: the second major metabolite of amobarbital in man. After oral administration of 14C-labeled amobarbital to healthy subjects, most of the radioactivity was recovered in urine and only 4-5% in feces over a period of 6 days. No unchanged amobarbital was excreted. Two major metabolites were found and isolated. One was 3'-hydroxyamobarbital, which has been previously identified by Maynert. The second could be identified as N-hydroxyamobarbital on the basis of its spectral and chemical properties."}
{"id": "PMID:1221", "title": "Spironolactone metabolism in man studied by gas chromatography-mass spectrometry.", "content": "Gas chromatography-mass spectrometry was used to identify metabolites of spironolactone in human blood and urine. In three healthy men about 20% of the radioactivity was excreted in the urine within 24 hr after an oral dose of [20-3H]spironolactone (200 mg + 200 muCi). About half of this radioactivity was extracted with chloroform at pH 3 and from this extract four stable metabolites were isolated by use of column and thin-layer chromatography. Two of these were the previously identified metabolites, canrenone (VII; 2.9% of dose) and the 6beta-hydroxy-sulfoxide (X; 1.8% of the dose). The remaining were the new metabolites, 15alpha-hydroxycanrenone (XI; 0.8% of dose) and the 6beta-hydroxy-thiomethyl derivatives (VI; 0.5% of dose). The principal water-soluble urinary metabolite was canrenoate ester glucuronide (XII; 4.5% of dose). In the 24- to 32-hr pooled serum, canrenone (VII) was the principal metabolite in the organic-extractable fraction; VI was present in appreciable amounts but X and XI were present at extremely low levels.", "contents": "Spironolactone metabolism in man studied by gas chromatography-mass spectrometry. Gas chromatography-mass spectrometry was used to identify metabolites of spironolactone in human blood and urine. In three healthy men about 20% of the radioactivity was excreted in the urine within 24 hr after an oral dose of [20-3H]spironolactone (200 mg + 200 muCi). About half of this radioactivity was extracted with chloroform at pH 3 and from this extract four stable metabolites were isolated by use of column and thin-layer chromatography. Two of these were the previously identified metabolites, canrenone (VII; 2.9% of dose) and the 6beta-hydroxy-sulfoxide (X; 1.8% of the dose). The remaining were the new metabolites, 15alpha-hydroxycanrenone (XI; 0.8% of dose) and the 6beta-hydroxy-thiomethyl derivatives (VI; 0.5% of dose). The principal water-soluble urinary metabolite was canrenoate ester glucuronide (XII; 4.5% of dose). In the 24- to 32-hr pooled serum, canrenone (VII) was the principal metabolite in the organic-extractable fraction; VI was present in appreciable amounts but X and XI were present at extremely low levels."}
{"id": "PMID:1223", "title": "Correlation of 14C-griseofulvin metabolism in rat liver microsomes, isolated perfused rat livers, and in rats with bile duct cannulas.", "content": "The metabolism of 14C-griseofulvin has been compared in rat liver microsomes, isolated perfused rat livers, and rats with bile duct cannulas. In all three preparations, 4-desmethylgriseofulvin and 6-desmethylgriseofulvin were the major metabolites. The ratio of total 4-desmethylgriseofulvin to 6-desmethylgriseofulvin formed was 1.20, 0.89, and 1.01 in liver microsomes, isolated perfused livers, and rats with bile duct cannulas, respectively. After a 7-min incubation with liver microsomes, most (96%) of the griseofulvin remained unchanged. Only small amounts of 4-desmethylgriseofulvin (1.26%) of dose) and 6-desmethylgriseofulvin (1.05% of dose) were formed. In isolated perfused liver, most of the drug (59% of dose) was excreted into bile within 4 hr, primarily as 4-desmethylgriseofulvin (24% of dose) and 6-methylgriseofulvin (24% of dose). In animals with bile duct cannulas, 65% of the dose was excreted into bile and 18% of the dose into urine within 4 hours. In bile, 32% of the dose was excreted as 4-desmethylgriseofulvin and 20% of the dose as 6-desmethylgriseofulvin, whereas in urine the drug was excreated predominantly as 6-desmethylgriseofulvin (13% of dose) with only a small amount of 4-desmethylgriseofulvin (1% of dose), during the first 4 hr. These results show that there is good correlation in the metabolic fate of 14C-griseofulvin in the liver microsomes, isolated perfused liver, and rats with bile duct cannulas. In addition to the similar ratio of 4-desmethylgriseofulvin to 6-desmethylgriseofulvin, there is also an agreement in the extent of metabolism and biliary excretion in isolated perfused liver and in rats with bile duct cannulas, which suggests that the isolated perfused liver is an important technique for studying drug metabolism in animals.", "contents": "Correlation of 14C-griseofulvin metabolism in rat liver microsomes, isolated perfused rat livers, and in rats with bile duct cannulas. The metabolism of 14C-griseofulvin has been compared in rat liver microsomes, isolated perfused rat livers, and rats with bile duct cannulas. In all three preparations, 4-desmethylgriseofulvin and 6-desmethylgriseofulvin were the major metabolites. The ratio of total 4-desmethylgriseofulvin to 6-desmethylgriseofulvin formed was 1.20, 0.89, and 1.01 in liver microsomes, isolated perfused livers, and rats with bile duct cannulas, respectively. After a 7-min incubation with liver microsomes, most (96%) of the griseofulvin remained unchanged. Only small amounts of 4-desmethylgriseofulvin (1.26%) of dose) and 6-desmethylgriseofulvin (1.05% of dose) were formed. In isolated perfused liver, most of the drug (59% of dose) was excreted into bile within 4 hr, primarily as 4-desmethylgriseofulvin (24% of dose) and 6-methylgriseofulvin (24% of dose). In animals with bile duct cannulas, 65% of the dose was excreted into bile and 18% of the dose into urine within 4 hours. In bile, 32% of the dose was excreted as 4-desmethylgriseofulvin and 20% of the dose as 6-desmethylgriseofulvin, whereas in urine the drug was excreated predominantly as 6-desmethylgriseofulvin (13% of dose) with only a small amount of 4-desmethylgriseofulvin (1% of dose), during the first 4 hr. These results show that there is good correlation in the metabolic fate of 14C-griseofulvin in the liver microsomes, isolated perfused liver, and rats with bile duct cannulas. In addition to the similar ratio of 4-desmethylgriseofulvin to 6-desmethylgriseofulvin, there is also an agreement in the extent of metabolism and biliary excretion in isolated perfused liver and in rats with bile duct cannulas, which suggests that the isolated perfused liver is an important technique for studying drug metabolism in animals."}
{"id": "PMID:1224", "title": "Oxidative biotransformation of 2-acetylaminofluorene in fetal and placental tissues of humans and monkeys. Correlations with aryl hydrocarbon hydroxylase activities.", "content": "The mixed-function oxidation of 14C-labled 2-acetylaminofluorene (AAF) was investigated in placental and fetal tissues of humans and monkeys (Macaca nemestrina) in vitro. The major metabolite formed in most tissues was 7-hydroxy-AAF. Rates of the hydroxylation reactions varied widely among the tissues investigated and were generally one to two orders of magnitude lower than those measured in rat hepatic tissues. High correlations among rates of 7-,5-, and 3- and between 1- and N-hydroxylations of AAF were observed. The latter two reactions were less responsive to inhibition by carbon monoxide. Rates of 3-hydroxylations of benzo[a]pyrene (BP) also were highly correlated with rates of 7-, 5-, and 3-hydroxylations of AAF but were not correlated with rates of 1- and N-hydroxylations in human placental microsomes. A lack of statistically significant correlations was observed among rates of many of these hydroxylation reactions studied in primate fetal tissues. Rates of 7-, 5-, and 3-hydroxylations of AAF were not statistically correlated with rates of 3-hydroxylation of BP in homogenates of primate fetal tissues in most instances, but statistically significant correlations among rates of 3-hydroxylation of BP and 1- and N-hydroxylations of AAF were observed in those preparations. The results suggested two separate mechanisms for the genetic control of rates of placental aromatic ring- and N-hydroxylation reactions as opposed to apparent multiple genetic controls for rates of these hydroxylation reactions in primate fetal tissues.", "contents": "Oxidative biotransformation of 2-acetylaminofluorene in fetal and placental tissues of humans and monkeys. Correlations with aryl hydrocarbon hydroxylase activities. The mixed-function oxidation of 14C-labled 2-acetylaminofluorene (AAF) was investigated in placental and fetal tissues of humans and monkeys (Macaca nemestrina) in vitro. The major metabolite formed in most tissues was 7-hydroxy-AAF. Rates of the hydroxylation reactions varied widely among the tissues investigated and were generally one to two orders of magnitude lower than those measured in rat hepatic tissues. High correlations among rates of 7-,5-, and 3- and between 1- and N-hydroxylations of AAF were observed. The latter two reactions were less responsive to inhibition by carbon monoxide. Rates of 3-hydroxylations of benzo[a]pyrene (BP) also were highly correlated with rates of 7-, 5-, and 3-hydroxylations of AAF but were not correlated with rates of 1- and N-hydroxylations in human placental microsomes. A lack of statistically significant correlations was observed among rates of many of these hydroxylation reactions studied in primate fetal tissues. Rates of 7-, 5-, and 3-hydroxylations of AAF were not statistically correlated with rates of 3-hydroxylation of BP in homogenates of primate fetal tissues in most instances, but statistically significant correlations among rates of 3-hydroxylation of BP and 1- and N-hydroxylations of AAF were observed in those preparations. The results suggested two separate mechanisms for the genetic control of rates of placental aromatic ring- and N-hydroxylation reactions as opposed to apparent multiple genetic controls for rates of these hydroxylation reactions in primate fetal tissues."}
{"id": "PMID:1225", "title": "Effect of 3-methylcholanthrene treatment on phenacetin O-dealkylation in several inbred mouse strains.", "content": "An increase in the metabolism of phenacetin to N-acetyl-p-aminophenol is correlated with benzo[a]pyrene hydroxylase induction by 3-methylcholanthrene among several inbred mouse strains. While the magnitude of induction of phenacetin O-dealkylation is considerably less than that of benzo[a]pyrene hydroxylation, the data indicate that in mice, the metabolism of these two substrates is under similar regulatory control.", "contents": "Effect of 3-methylcholanthrene treatment on phenacetin O-dealkylation in several inbred mouse strains. An increase in the metabolism of phenacetin to N-acetyl-p-aminophenol is correlated with benzo[a]pyrene hydroxylase induction by 3-methylcholanthrene among several inbred mouse strains. While the magnitude of induction of phenacetin O-dealkylation is considerably less than that of benzo[a]pyrene hydroxylation, the data indicate that in mice, the metabolism of these two substrates is under similar regulatory control."}
{"id": "PMID:1226", "title": "Further studies of metyrapone effects upon anilide hydroxylation.", "content": "The enhancing effect of metyrapone upon the p-hydroxylation of acetanilide has been confirmed with the use of a new gas-chromatographic method for the determination of acetaminophen. This effect has been shown not to be due to inhibition of hydrolysis of acetaminophen or interference with its determination, or to preferential formation of other phenolic metabolites. This effect of metyrapone is remarkably substrate-specific: phenol formation from the homologues of acetanilide, formanilide and propionanilide, and that from the sulfonamide analog of acetanilide, methanesulfonanilide, is inhibited by metyrapone over the concentration range in which acetanilide hydroxylation is enhanced. The same substrate specificity was observed when the modifier was acetophenone. alpha,alpha'-Dipyridyl, however, enhances phenol formation from all three carbonacylanilides, but does not affect that from methanesulfonanilide.", "contents": "Further studies of metyrapone effects upon anilide hydroxylation. The enhancing effect of metyrapone upon the p-hydroxylation of acetanilide has been confirmed with the use of a new gas-chromatographic method for the determination of acetaminophen. This effect has been shown not to be due to inhibition of hydrolysis of acetaminophen or interference with its determination, or to preferential formation of other phenolic metabolites. This effect of metyrapone is remarkably substrate-specific: phenol formation from the homologues of acetanilide, formanilide and propionanilide, and that from the sulfonamide analog of acetanilide, methanesulfonanilide, is inhibited by metyrapone over the concentration range in which acetanilide hydroxylation is enhanced. The same substrate specificity was observed when the modifier was acetophenone. alpha,alpha'-Dipyridyl, however, enhances phenol formation from all three carbonacylanilides, but does not affect that from methanesulfonanilide."}
{"id": "PMID:1227", "title": "Nature and fate of insecticide residues inhaled by rats in cigarette smoke.", "content": "Radioactive carbaryl, carbofuran, parathion, leptophos, and DDT were added to cigarettes and the mainstream smoke was directed to the lungs of rats via the trachea. Total radiocarbon transfer to the lungs ranged from 9 to 15% of that in the tobacco burned during a smoking process involving eight 5-ml puffs. Exhalation of 14C residues during this time was 24 to 30% of that inhaled with all insecticides except carbofuran, of which 42% of the residues was exhaled. After 5 hr, total exhalation of the consumed radiocarbon was 35% for parathion, 65% for carbofuran, and approximately 50% for the other products. The nature of the 14C residues inhaled, their urinary and fecal excretion, and their deposition in and dissipation from various organs and tissues are presented.", "contents": "Nature and fate of insecticide residues inhaled by rats in cigarette smoke. Radioactive carbaryl, carbofuran, parathion, leptophos, and DDT were added to cigarettes and the mainstream smoke was directed to the lungs of rats via the trachea. Total radiocarbon transfer to the lungs ranged from 9 to 15% of that in the tobacco burned during a smoking process involving eight 5-ml puffs. Exhalation of 14C residues during this time was 24 to 30% of that inhaled with all insecticides except carbofuran, of which 42% of the residues was exhaled. After 5 hr, total exhalation of the consumed radiocarbon was 35% for parathion, 65% for carbofuran, and approximately 50% for the other products. The nature of the 14C residues inhaled, their urinary and fecal excretion, and their deposition in and dissipation from various organs and tissues are presented."}
{"id": "PMID:1228", "title": "Absorption and disposition of 2-[4-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid, WIN 35,833, in rats, monkeys, and men.", "content": "2-[4-(2,2-Dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid, Win 35,833, was readily absorbed after oral administration; in rats, rhesus monkeys, and human volunteers, peak concentrations of drug in plasma were attained within 2 hr of medication. The time-concentration curve of administered drug was biphasic in monkeys and men, while in rats the kinetics of a one-compartment model were observed. Distribution studies of 14C-labeled drug in the rat showed that most of the radioactivity was excreted in the feces and that significant quantities of 14C were sequestered by depot fat. Monkeys and human subjects both eliminated Win 35,833 primarily through the kidneys. The drug was excreted in rat bile and human urine, both as the free acid and conjugated with glucuronic acid. At physiological concentrations, Win 35,833 was extensively bound to rat, monkey, and human plasma proteins. A gas-chromatographic method for the analysis of drug in plasma, urine, or bile gave a linear relationship between peak height ratios and concentrations, in the range of 1-60 mug/ml.", "contents": "Absorption and disposition of 2-[4-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid, WIN 35,833, in rats, monkeys, and men. 2-[4-(2,2-Dichlorocyclopropyl)phenoxy]-2-methylpropanoic acid, Win 35,833, was readily absorbed after oral administration; in rats, rhesus monkeys, and human volunteers, peak concentrations of drug in plasma were attained within 2 hr of medication. The time-concentration curve of administered drug was biphasic in monkeys and men, while in rats the kinetics of a one-compartment model were observed. Distribution studies of 14C-labeled drug in the rat showed that most of the radioactivity was excreted in the feces and that significant quantities of 14C were sequestered by depot fat. Monkeys and human subjects both eliminated Win 35,833 primarily through the kidneys. The drug was excreted in rat bile and human urine, both as the free acid and conjugated with glucuronic acid. At physiological concentrations, Win 35,833 was extensively bound to rat, monkey, and human plasma proteins. A gas-chromatographic method for the analysis of drug in plasma, urine, or bile gave a linear relationship between peak height ratios and concentrations, in the range of 1-60 mug/ml."}
{"id": "PMID:1229", "title": "The gastrointestinal absorption of methadone in the rat.", "content": "The absorption of dl-methadone from the gastrointestinal tract of the Sprague-Dawley rat was examined by the in vivo segment technique. Duodenal absorption, measured as a function of time and dose, followed first-order kinetics with a half-life of 15.6 min. Absorption was not influenced by prior or concomitant administration of a variety of drugs. Absorption from other regions of the intestine was similar to that from the duodenum; in contrast, absorption from the stomach was markedly slower. Gastric absorption was increased by alkalinization of stomach contents but was still considerably slower than from the duodenum. Gastric emptying of methadone appears to be the rate-limiting step in the overall gastrointestinal absorption of the drug, since the rate of emptying following intubation of the drug into the stomach was also considerably slower than the rate of duodenal absorption.", "contents": "The gastrointestinal absorption of methadone in the rat. The absorption of dl-methadone from the gastrointestinal tract of the Sprague-Dawley rat was examined by the in vivo segment technique. Duodenal absorption, measured as a function of time and dose, followed first-order kinetics with a half-life of 15.6 min. Absorption was not influenced by prior or concomitant administration of a variety of drugs. Absorption from other regions of the intestine was similar to that from the duodenum; in contrast, absorption from the stomach was markedly slower. Gastric absorption was increased by alkalinization of stomach contents but was still considerably slower than from the duodenum. Gastric emptying of methadone appears to be the rate-limiting step in the overall gastrointestinal absorption of the drug, since the rate of emptying following intubation of the drug into the stomach was also considerably slower than the rate of duodenal absorption."}
{"id": "PMID:1230", "title": "Biliary excretion of colchicine in newborn rats.", "content": "The 24-hr LD50 of colchicine in newborn rats is 0.24 mg/kg, which is about 1/10 that observed in the adult. The 24-hr LD50 of colchicine was relatively constant in rats over 25 days of age. In an attempt to determine the mechanism of the increased sensitivity of the newborn rat to the toxic action of colchicine, the distribution of 3H after the administration of 3H-colchicine (0.1 mg/kg) was measured in 10- and 35-day-old rats. The concentration of 3H was higher in all tissues of the newborn than the adult after ip administration, suggesting an immaturity in the pathway for colchicine elimination. After iv administration, radioactivity disappeared much more slowly from the plasma of the newborn rat than from the adult. This was due to a lower capacity of the liver of the newborn to concentrate colchicine and to excrete it into the bile. Development of the hepatic excretory mechanism responsible for excretion of colchicine occurred at the same age as did the increase in LD50. These results suggest that colchicine is more toxic in the newborn because the drug remains in the body for a longer time due to immaturity of the liver excretory process.", "contents": "Biliary excretion of colchicine in newborn rats. The 24-hr LD50 of colchicine in newborn rats is 0.24 mg/kg, which is about 1/10 that observed in the adult. The 24-hr LD50 of colchicine was relatively constant in rats over 25 days of age. In an attempt to determine the mechanism of the increased sensitivity of the newborn rat to the toxic action of colchicine, the distribution of 3H after the administration of 3H-colchicine (0.1 mg/kg) was measured in 10- and 35-day-old rats. The concentration of 3H was higher in all tissues of the newborn than the adult after ip administration, suggesting an immaturity in the pathway for colchicine elimination. After iv administration, radioactivity disappeared much more slowly from the plasma of the newborn rat than from the adult. This was due to a lower capacity of the liver of the newborn to concentrate colchicine and to excrete it into the bile. Development of the hepatic excretory mechanism responsible for excretion of colchicine occurred at the same age as did the increase in LD50. These results suggest that colchicine is more toxic in the newborn because the drug remains in the body for a longer time due to immaturity of the liver excretory process."}
{"id": "PMID:1231", "title": "Disposition in rats of a polyoxypropylene-polyoxyethylene copolymer used in plasma fractionation.", "content": "A polyoxypropylene-polyoxyethylene block copolymer of about 4750 daltons (Poloxamer 108, Pluronic F-38) used in a new protein fractionation procedure may be infused into patients receiving therapeutic plasma fractions. We studied the disposition and pharmacokinetics of Poloxamer 108 in rats as an initial step towards understanding its behavior in man. After iv administration in rats, about 94% of 7 or 100 mg/kg doses of ethylene-14C-labeled polymer was excreted in the urine in 3 days. About 6% of the label appeared in feces. Erythrocyte membranes were not permeable to the polymer, and only the parent compound was demonstrable in urine. Twenty hours after dosing, small residues were detectable only in the kidney, liver, small intestine, and carcass. The third phase of the plasma disappearance pattern was evident only at the larger dose, but plasma disappearance kinetics were independent of the dose in the range used here. Thus, most of poloxamer 108 was eliminated rapidly in rats by renal excretion, and a smaller portion probably was removed by biliary excretion. These results will be applied to continuing studies of Poloxamer 108 disposition in man.", "contents": "Disposition in rats of a polyoxypropylene-polyoxyethylene copolymer used in plasma fractionation. A polyoxypropylene-polyoxyethylene block copolymer of about 4750 daltons (Poloxamer 108, Pluronic F-38) used in a new protein fractionation procedure may be infused into patients receiving therapeutic plasma fractions. We studied the disposition and pharmacokinetics of Poloxamer 108 in rats as an initial step towards understanding its behavior in man. After iv administration in rats, about 94% of 7 or 100 mg/kg doses of ethylene-14C-labeled polymer was excreted in the urine in 3 days. About 6% of the label appeared in feces. Erythrocyte membranes were not permeable to the polymer, and only the parent compound was demonstrable in urine. Twenty hours after dosing, small residues were detectable only in the kidney, liver, small intestine, and carcass. The third phase of the plasma disappearance pattern was evident only at the larger dose, but plasma disappearance kinetics were independent of the dose in the range used here. Thus, most of poloxamer 108 was eliminated rapidly in rats by renal excretion, and a smaller portion probably was removed by biliary excretion. These results will be applied to continuing studies of Poloxamer 108 disposition in man."}
{"id": "PMID:1232", "title": "Uptake and disposition of aldrin and dieldrin by isolated perfused rabbit lung.", "content": "The uptake, metabolism, and release of aldrin and dieldrin by the lungs were studied by use of isolated perfused rabbit lungs that were artificially ventilated and perfused through the pulmonary artery. Both recirculating and single-pass experiments were conducted using an artificial medium as perfusate. Aldrin accumulated in the lung from the perfusate through two distinct phases of uptake: a rapid phase involving simple diffusion and nonspecific binding and a slower phase representing its metabolic turnover as dieldrin. Dieldrin was not metabolized but accumulated in the lungs by a saturable and a nonsaturable process. Single-pass experiments with aldrin indicated that the initial velocity of uptake could be fitted to one component and a constant representing the rate of metabolism. Uptake of dieldrin was biphasic: one phase independent of the perfusate concentration and the other saturable with respect to the perfusate concentration. By the application of Michaelis-Menten kinetics, the maximum amount of dieldrin accumulation attributable to the saturable component was calculated to be 0.64 mumol/lung. Our results indicate that the accumulation of these chlorinated xenobiotics takes place through the processes of simple diffusion followed by nonspecific tissue binding. There was no evidence for irreversible binding of aldrin or dieldrin, its epoxide, in the lung. While the lung plays a role in metabolizing aldrin to dieldrin followed by a transient storage, neither substrate has the potential for long-term storage in the lung.", "contents": "Uptake and disposition of aldrin and dieldrin by isolated perfused rabbit lung. The uptake, metabolism, and release of aldrin and dieldrin by the lungs were studied by use of isolated perfused rabbit lungs that were artificially ventilated and perfused through the pulmonary artery. Both recirculating and single-pass experiments were conducted using an artificial medium as perfusate. Aldrin accumulated in the lung from the perfusate through two distinct phases of uptake: a rapid phase involving simple diffusion and nonspecific binding and a slower phase representing its metabolic turnover as dieldrin. Dieldrin was not metabolized but accumulated in the lungs by a saturable and a nonsaturable process. Single-pass experiments with aldrin indicated that the initial velocity of uptake could be fitted to one component and a constant representing the rate of metabolism. Uptake of dieldrin was biphasic: one phase independent of the perfusate concentration and the other saturable with respect to the perfusate concentration. By the application of Michaelis-Menten kinetics, the maximum amount of dieldrin accumulation attributable to the saturable component was calculated to be 0.64 mumol/lung. Our results indicate that the accumulation of these chlorinated xenobiotics takes place through the processes of simple diffusion followed by nonspecific tissue binding. There was no evidence for irreversible binding of aldrin or dieldrin, its epoxide, in the lung. While the lung plays a role in metabolizing aldrin to dieldrin followed by a transient storage, neither substrate has the potential for long-term storage in the lung."}
{"id": "PMID:1233", "title": "Kinetic and spectral studies of type I and type II compounds with rat hepatic microsomes in the presence of the major metabolite of diphenylhydantoin.", "content": "The nature of the inhibitory effects of the major metabolite of diphenylhydantoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), on the in vitro metabolism of ethylmorphine and aniline by rat hepatic microsomes was examined. The N-demethylation of ethylmorphine was competitively inhibited by HPPH, whereas inhibition of the hydroxylation of aniline was not competitive. The spectrum produced by HPPH when added to microsomal suspensions does not resemble the classical type I or type II spectra, but rather a reversed type I spectrum. Spectral evidence is presented indicating that HPPH also diminishes the magnitude of the spectral change produced by type I and II compounds.", "contents": "Kinetic and spectral studies of type I and type II compounds with rat hepatic microsomes in the presence of the major metabolite of diphenylhydantoin. The nature of the inhibitory effects of the major metabolite of diphenylhydantoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), on the in vitro metabolism of ethylmorphine and aniline by rat hepatic microsomes was examined. The N-demethylation of ethylmorphine was competitively inhibited by HPPH, whereas inhibition of the hydroxylation of aniline was not competitive. The spectrum produced by HPPH when added to microsomal suspensions does not resemble the classical type I or type II spectra, but rather a reversed type I spectrum. Spectral evidence is presented indicating that HPPH also diminishes the magnitude of the spectral change produced by type I and II compounds."}
{"id": "PMID:1234", "title": "Change in the kinetics of sulphacetamide tissue distribution in Walker tumor-bearing rats.", "content": "The effect of Walker tumor on sulphacetamide distribution was studied in rats 21 days after tumor implantation in a hind leg. After oral administration of sulphacetamide (5 and 20 min), the concentration of the drug was found to be lower in the plasma and liver of tumor-bearing rats when compared with that of control group. However, 90 min after sulphacetamide administration, the concentration of the drug in these same tissues was found to be higher in tumor-bearing rats than in control animals. Whereas the tumor had no apparent effect on sulphacetamide concentration in the brain, drug concentrations in the fat tissue of tumor-bearing rats were constantly higher than those of control animals. These changes in sulphacentamide disposition kinetics could be explained in part by delay in gastrointestinal absorption of the drug. Contrary to what was observed after oral administration, constantly higher drug concentrations were found in the plasma of tumor-bearing rats after iv injection of sulphacetamide. Furthermore, the half-life of sulphacetamide in these same animals was much higher than in control animals. It is concluded that, in Walker tumor-bearing rats, there are changes in the kinetics of sulphacetamide which are functions of the route of administration of the drug.", "contents": "Change in the kinetics of sulphacetamide tissue distribution in Walker tumor-bearing rats. The effect of Walker tumor on sulphacetamide distribution was studied in rats 21 days after tumor implantation in a hind leg. After oral administration of sulphacetamide (5 and 20 min), the concentration of the drug was found to be lower in the plasma and liver of tumor-bearing rats when compared with that of control group. However, 90 min after sulphacetamide administration, the concentration of the drug in these same tissues was found to be higher in tumor-bearing rats than in control animals. Whereas the tumor had no apparent effect on sulphacetamide concentration in the brain, drug concentrations in the fat tissue of tumor-bearing rats were constantly higher than those of control animals. These changes in sulphacentamide disposition kinetics could be explained in part by delay in gastrointestinal absorption of the drug. Contrary to what was observed after oral administration, constantly higher drug concentrations were found in the plasma of tumor-bearing rats after iv injection of sulphacetamide. Furthermore, the half-life of sulphacetamide in these same animals was much higher than in control animals. It is concluded that, in Walker tumor-bearing rats, there are changes in the kinetics of sulphacetamide which are functions of the route of administration of the drug."}
{"id": "PMID:1235", "title": "Cytochrome P-450 measurement in rat liver homogenate and microsomes. Its use for correction of microsomal losses incurred by differential centrifugation.", "content": "Cytochrome P-450 was assayed in rat liver homogenates and microsomes in order to calculate microsomal recoveries and correct for losses during ultracentrifugation or sedimentation in presence of CaCl2. The values obtained for corrected microsomal protein in untreated female Sprague-Dawley rats were between 40 and 50 mg/g of liver. The assay of cytochrome P-450 in liver homogenate is accurate enough to calculate a reproducible recovery factor. The value of the method lies in its rapidity, its capacity to correct over a wide range of losses, and its capacity to yield reliable values of the total microsomal protein mass. The limits of this method include overestimation of homogenate cytochrome P-450 and inability to correct for nonmicrosomal protein contamination. Overestimation of cytochrome P-450 can be corrected by measuring the difference in absorbance between 450 and 510 nm with the extinction coefficient of 100 mM-1cm-1. To be accurate, cytochrome P-450 determination on microsomes must be done at protein concentrations of about 3 mg/ml. The error inherent to the method may be kept constant and minimal. The use of correction for microsomal losses is recommended in order to obtain uniformity between results from various laboratories and adequate correlation with in vivo studies of microsomal functions.", "contents": "Cytochrome P-450 measurement in rat liver homogenate and microsomes. Its use for correction of microsomal losses incurred by differential centrifugation. Cytochrome P-450 was assayed in rat liver homogenates and microsomes in order to calculate microsomal recoveries and correct for losses during ultracentrifugation or sedimentation in presence of CaCl2. The values obtained for corrected microsomal protein in untreated female Sprague-Dawley rats were between 40 and 50 mg/g of liver. The assay of cytochrome P-450 in liver homogenate is accurate enough to calculate a reproducible recovery factor. The value of the method lies in its rapidity, its capacity to correct over a wide range of losses, and its capacity to yield reliable values of the total microsomal protein mass. The limits of this method include overestimation of homogenate cytochrome P-450 and inability to correct for nonmicrosomal protein contamination. Overestimation of cytochrome P-450 can be corrected by measuring the difference in absorbance between 450 and 510 nm with the extinction coefficient of 100 mM-1cm-1. To be accurate, cytochrome P-450 determination on microsomes must be done at protein concentrations of about 3 mg/ml. The error inherent to the method may be kept constant and minimal. The use of correction for microsomal losses is recommended in order to obtain uniformity between results from various laboratories and adequate correlation with in vivo studies of microsomal functions."}
{"id": "PMID:1243", "title": "Identification of \"big\" human placental lactogen in placenta and serum.", "content": "Because of increasing evidence for the heterogeneity of polypeptide hormones, studies of the molecular species of human placental lactogen (hPL) were initiated. When extracts of freshly delivered human placentas were passed over Sephadex G-100 in 0.05M ammonium carbonate, three immunoreactive peaks were detected. In addition to a peak corresponding to native hPL (Kav = 0.39) and one in the void volume, a consistent peak which eluted before hPL (Kav = 0.20) was present. The latter represented 2-25% of total hormonal activity and could be rerun without significant conversion to hPL. In 8M urea, the peak continued to behave as a large molecular weight form on both Sephadex chromatography and on polyacrylamide disc gel electrophoresis. Extraction procedures at both neutral and alkaline pH produced similar quantities of the larger material. [125I]iodo-hPL was not converted to the larger form by the conditions of extraction or analysis. These properties are consistent with a larger molecular weight, non-aggregated form of hPL. In comparison with the native hormone, the idsplacement curves for the larger form were parallel in radioimmunoassay studies. Sera obtained from pregnant women during various stages of gestation also showed consistent evidence for a large molecular weight form of the hormone. These observations provide direct evidence, both in placental tissue and in serum for \"big\" hPL.", "contents": "Identification of \"big\" human placental lactogen in placenta and serum. Because of increasing evidence for the heterogeneity of polypeptide hormones, studies of the molecular species of human placental lactogen (hPL) were initiated. When extracts of freshly delivered human placentas were passed over Sephadex G-100 in 0.05M ammonium carbonate, three immunoreactive peaks were detected. In addition to a peak corresponding to native hPL (Kav = 0.39) and one in the void volume, a consistent peak which eluted before hPL (Kav = 0.20) was present. The latter represented 2-25% of total hormonal activity and could be rerun without significant conversion to hPL. In 8M urea, the peak continued to behave as a large molecular weight form on both Sephadex chromatography and on polyacrylamide disc gel electrophoresis. Extraction procedures at both neutral and alkaline pH produced similar quantities of the larger material. [125I]iodo-hPL was not converted to the larger form by the conditions of extraction or analysis. These properties are consistent with a larger molecular weight, non-aggregated form of hPL. In comparison with the native hormone, the idsplacement curves for the larger form were parallel in radioimmunoassay studies. Sera obtained from pregnant women during various stages of gestation also showed consistent evidence for a large molecular weight form of the hormone. These observations provide direct evidence, both in placental tissue and in serum for \"big\" hPL."}
{"id": "PMID:1244", "title": "The water-to-air transfer of 35SO4= by bursting bubbles.", "content": "The transfer of 35SO4= from water to air by bursting bubbles was studied as a function of three levels each of three variables in a bubbling solution. The variables were pH, surfactant concentration, and Na2 35SO4 concentration. One combination of the above variables was also studied at three different temperatures. Sterile water solutions containing different combinations of the above factors and a fixed amount of 22NaCl were bubbled in an enclosure for 1 hour. After bubbling, samples of the aerosol produced, the larger drops that fell out of the air, and the bulk solution were collected and assayed for their 35S and 22Na content using liquid scintillation counting. The 35S/22Na enrichment for each droplet sample as compared to the ratio for the bulk solution was determined, and it was found to be dependent upon the combination of the factor levels being bubbled. Both positive and negative enrichments were found, with large positive enrichments being found consistently only for the highest value of surfactant concentration. The temperature study showed no significant enrichment differences for any of the three temperatures studied.", "contents": "The water-to-air transfer of 35SO4= by bursting bubbles. The transfer of 35SO4= from water to air by bursting bubbles was studied as a function of three levels each of three variables in a bubbling solution. The variables were pH, surfactant concentration, and Na2 35SO4 concentration. One combination of the above variables was also studied at three different temperatures. Sterile water solutions containing different combinations of the above factors and a fixed amount of 22NaCl were bubbled in an enclosure for 1 hour. After bubbling, samples of the aerosol produced, the larger drops that fell out of the air, and the bulk solution were collected and assayed for their 35S and 22Na content using liquid scintillation counting. The 35S/22Na enrichment for each droplet sample as compared to the ratio for the bulk solution was determined, and it was found to be dependent upon the combination of the factor levels being bubbled. Both positive and negative enrichments were found, with large positive enrichments being found consistently only for the highest value of surfactant concentration. The temperature study showed no significant enrichment differences for any of the three temperatures studied."}
{"id": "PMID:1245", "title": "Differential effects of phenobarbital and pentobarbital on isolated nervous tissue.", "content": "Epileptiform after discharges evoked by repetitive electrical stimulation of chronically isolated cortical slabs (cat) were shortened by low doses of phenobarbital but not affected by hypnotic doses of pentobarbital. Both pentobarbital and phenobarbital raised threshold and lowered spike amplitude in isolated sciatic nerves. The action of both drugs was increased by reducing Na in the medium and by decreasing the Ringer's pH. Similar to the action of other general anesthetics, the axonal effect of pentobarbital was enhanced by D2O replacement for H2O in the Ringer's (suggesting that tissue water is involved in pentobarbital action), whereas D2O replacement did not modify the action of phenobarbital or of local anesthetics. These results suggest that the varying in vivo effects of pentobarbital and phenobarbital may be due to a difference in their action upon excitable membranes (rather than to a different regional distribution in brain).", "contents": "Differential effects of phenobarbital and pentobarbital on isolated nervous tissue. Epileptiform after discharges evoked by repetitive electrical stimulation of chronically isolated cortical slabs (cat) were shortened by low doses of phenobarbital but not affected by hypnotic doses of pentobarbital. Both pentobarbital and phenobarbital raised threshold and lowered spike amplitude in isolated sciatic nerves. The action of both drugs was increased by reducing Na in the medium and by decreasing the Ringer's pH. Similar to the action of other general anesthetics, the axonal effect of pentobarbital was enhanced by D2O replacement for H2O in the Ringer's (suggesting that tissue water is involved in pentobarbital action), whereas D2O replacement did not modify the action of phenobarbital or of local anesthetics. These results suggest that the varying in vivo effects of pentobarbital and phenobarbital may be due to a difference in their action upon excitable membranes (rather than to a different regional distribution in brain)."}
{"id": "PMID:1246", "title": "The reaction of horse-liver alcohol dehydrogenase with glyoxal.", "content": "Horse liver alcohol dehydrogenase was reacted with glyoxal at different pH values ranging from 6.0 to 9.0. At pH 9.0 the enzyme undergoes a rapid activation over the first minutes of reaction, followed by a decline of activity, which reaches 10% of that of the native enzyme. Chemical analysis of the inactivated enzyme after sodium borohydride reduction shows that 11 argi-ine and 11 lysine residues per mole are modified. At pH 7.7 the enzyme activity increases during the first hour of the reaction with glyoxal and then decreases slowly. Chemical analysis shows that 4 arginine and 3 lysine residues per mole are modified in the enzyme at the maximum of activation. At pH 7.0 the enzyme undergoes a 4-fold activation. Chemical analysis shows that in this activated enzyme 3 lysine and no arginine residues per mole have been modified. Steady-state kinetic analysis suggests that the activated enzyme is not subjected to substrate inhibition and that its Michaelis constant for ethanol is three times larger than that of the native enzyme. The possible role of arginine and lysine residues in the catalytic function of liver alcohol dehydrogenase is discussed.", "contents": "The reaction of horse-liver alcohol dehydrogenase with glyoxal. Horse liver alcohol dehydrogenase was reacted with glyoxal at different pH values ranging from 6.0 to 9.0. At pH 9.0 the enzyme undergoes a rapid activation over the first minutes of reaction, followed by a decline of activity, which reaches 10% of that of the native enzyme. Chemical analysis of the inactivated enzyme after sodium borohydride reduction shows that 11 argi-ine and 11 lysine residues per mole are modified. At pH 7.7 the enzyme activity increases during the first hour of the reaction with glyoxal and then decreases slowly. Chemical analysis shows that 4 arginine and 3 lysine residues per mole are modified in the enzyme at the maximum of activation. At pH 7.0 the enzyme undergoes a 4-fold activation. Chemical analysis shows that in this activated enzyme 3 lysine and no arginine residues per mole have been modified. Steady-state kinetic analysis suggests that the activated enzyme is not subjected to substrate inhibition and that its Michaelis constant for ethanol is three times larger than that of the native enzyme. The possible role of arginine and lysine residues in the catalytic function of liver alcohol dehydrogenase is discussed."}
{"id": "PMID:1247", "title": "The conformational oscillation of delta-chymotrypsin involvement of methionine-192.", "content": "In delta-chymotrypsin the reactivity of methionine-192 towards p-nitrophenacyl bromide is strongly reduced when the alpha-amino group of isoleucine-16 has been acetylated. Since acetylation of isoleucine-16 brings delta-chymotrypsin to a conformation similar to its alkaline one this suggests that methionine-192 should present an impaired reactivity in the alkaline conformation of the protein. It is indeed observed that its chemical reactivity as a function of pH depends on the ionization state of the alpha-amino group of isoleucine-16 (pKapp 9 at 15 degrees C) as does the structure of the enzyme. Reciprocally, after chemical reaction of methionine-192 with hydrogen peroxide, isoleucine-16 presents a slower rate of reaction with fluorescamine than when methionine-192 is free. As a result of methionine-192 oxidation the apparent pK of the alkaline transition is shifted from 9 to about 11 at 15 degrees C. This is reflected in the disappearance of the lag phase previously observed for the initial activity of the enzyme when it is incubated at alkaline pH [Eur. J. Biochem. (1973) 39,293-300]. The absence of chemical reactivity of methionine-192 in the alkaline state of the enzyme is confirmed by the appearance of a lag phase in the reaction of the protein with iodoacetate after an incubation at alkaline pH. Such a lag phase does not appear when this incubation is carried out at neutral pH. Since this lag phase is similar to that which shows up in the activity during the isomerization of the enzyme from its alkaline to its neutral state, the present data are interpreted as implying a concerted movement of isoleucine-16 and methionine-192 during this isomerization process. They also indicate that in the alkaline form of the enzyme methionine-192 has moved back into the interior of the protein. Since the spectroscopic properties of the zymogen and of the high-pH form of the enzyme are similar they suggest that methionine-192 occupies in the alkaline conformation of the enzyme a similar position as it does in the zymogen.", "contents": "The conformational oscillation of delta-chymotrypsin involvement of methionine-192. In delta-chymotrypsin the reactivity of methionine-192 towards p-nitrophenacyl bromide is strongly reduced when the alpha-amino group of isoleucine-16 has been acetylated. Since acetylation of isoleucine-16 brings delta-chymotrypsin to a conformation similar to its alkaline one this suggests that methionine-192 should present an impaired reactivity in the alkaline conformation of the protein. It is indeed observed that its chemical reactivity as a function of pH depends on the ionization state of the alpha-amino group of isoleucine-16 (pKapp 9 at 15 degrees C) as does the structure of the enzyme. Reciprocally, after chemical reaction of methionine-192 with hydrogen peroxide, isoleucine-16 presents a slower rate of reaction with fluorescamine than when methionine-192 is free. As a result of methionine-192 oxidation the apparent pK of the alkaline transition is shifted from 9 to about 11 at 15 degrees C. This is reflected in the disappearance of the lag phase previously observed for the initial activity of the enzyme when it is incubated at alkaline pH [Eur. J. Biochem. (1973) 39,293-300]. The absence of chemical reactivity of methionine-192 in the alkaline state of the enzyme is confirmed by the appearance of a lag phase in the reaction of the protein with iodoacetate after an incubation at alkaline pH. Such a lag phase does not appear when this incubation is carried out at neutral pH. Since this lag phase is similar to that which shows up in the activity during the isomerization of the enzyme from its alkaline to its neutral state, the present data are interpreted as implying a concerted movement of isoleucine-16 and methionine-192 during this isomerization process. They also indicate that in the alkaline form of the enzyme methionine-192 has moved back into the interior of the protein. Since the spectroscopic properties of the zymogen and of the high-pH form of the enzyme are similar they suggest that methionine-192 occupies in the alkaline conformation of the enzyme a similar position as it does in the zymogen."}
{"id": "PMID:1248", "title": "Investigations on the kinetic mechanism of octopine dehydrogenase. 1. Steady-state kinetics.", "content": "The kinetic mechanism of action of octopine dehydrogenase was investigated. This enzyme catalyses the reversible dehydrogenation of D-octopine to L-arginine and pyruvate, in the presence of nicotinamide-adenine dinucleotide. Initial velocity and product inhibition studies were carried out in both directions. Most of the results are consistent with a bi-ter sequential mechanism where NAD+ binds first to the enzyme followed by D-octopine, and the products are released in the order L-arginine, pyruvate and NADH. Various kinetic parameters were determined for each reactant at 33 degrees C, at pH 9.6 for NAD reduction, at pH 6.6 for NADH oxidation.", "contents": "Investigations on the kinetic mechanism of octopine dehydrogenase. 1. Steady-state kinetics. The kinetic mechanism of action of octopine dehydrogenase was investigated. This enzyme catalyses the reversible dehydrogenation of D-octopine to L-arginine and pyruvate, in the presence of nicotinamide-adenine dinucleotide. Initial velocity and product inhibition studies were carried out in both directions. Most of the results are consistent with a bi-ter sequential mechanism where NAD+ binds first to the enzyme followed by D-octopine, and the products are released in the order L-arginine, pyruvate and NADH. Various kinetic parameters were determined for each reactant at 33 degrees C, at pH 9.6 for NAD reduction, at pH 6.6 for NADH oxidation."}
{"id": "PMID:1249", "title": "The catalytic mechanism of carbonic anhydrase. Hydrogen-isotope effects on the kinetic parameters of the human C isoenzyme.", "content": "1. The steady-state kinetics of the interconversion of CO2 and HCO3 catalyzed by human carbonic anhydrase C was studied using 1H2O and 2H2O as solvents. The pH-independent parts of the parameters k(cat) and Km are 3-4 times larger in 1H2O than in 2H2O for both directions of the reaction, while the ratios k(cat)/Km show much smaller isotope effects. With either CO2 or HCO3 as substrate the major pH dependence is observed in k(cat), while Km appears independent of pH. The pKa value characterizing the pH-rate profiles is approximately 0.5 unit larger in 2H2O than in 1H2O. 2. The hydrolysis of p-nitrophenyl acetate catalyzed by human carbonic anhudrase C is approximately 35% faster in 2H2O than in 1H2O. In both solvents the pKa values of the pH-rate profiles are similar to those observed for the CO2-HCO3 interconversion. 3. It is tentatively proposed that the rate-limiting step at saturating concentrations of CO2 or HCO3 is an intramolecular proton transfer between two ionizing groups in the active site. It cannot be decided whether the transformation between enzyme-bound CO2 and HCO3 involves a proton trnasfer or not.", "contents": "The catalytic mechanism of carbonic anhydrase. Hydrogen-isotope effects on the kinetic parameters of the human C isoenzyme. 1. The steady-state kinetics of the interconversion of CO2 and HCO3 catalyzed by human carbonic anhydrase C was studied using 1H2O and 2H2O as solvents. The pH-independent parts of the parameters k(cat) and Km are 3-4 times larger in 1H2O than in 2H2O for both directions of the reaction, while the ratios k(cat)/Km show much smaller isotope effects. With either CO2 or HCO3 as substrate the major pH dependence is observed in k(cat), while Km appears independent of pH. The pKa value characterizing the pH-rate profiles is approximately 0.5 unit larger in 2H2O than in 1H2O. 2. The hydrolysis of p-nitrophenyl acetate catalyzed by human carbonic anhudrase C is approximately 35% faster in 2H2O than in 1H2O. In both solvents the pKa values of the pH-rate profiles are similar to those observed for the CO2-HCO3 interconversion. 3. It is tentatively proposed that the rate-limiting step at saturating concentrations of CO2 or HCO3 is an intramolecular proton transfer between two ionizing groups in the active site. It cannot be decided whether the transformation between enzyme-bound CO2 and HCO3 involves a proton trnasfer or not."}
{"id": "PMID:1250", "title": "Purification and properties of isoenzymes of cinnamyl-alcohol dehydrogenase from soybean-cell-suspension cultures.", "content": "Two isoenzymes of an NADP+ -dependent cinnamyl alcohol dehydrogenase and an NAD+ - dependent aliphatic alcohol dehydrogenase were extracted from cell suspension cultures of soybean (Glycine max L., var. Mandarin) which form lignin during growth. These enzymes could be separated from each other by chromatography on DEAE-cellulose and hydroxyapatite. The cinnamyl alcohol dehydrogenase isoenzymes were partially purified by (NH4)2SO4 fractionation, and column chromatography on DEAE-cellulose, Sephadex G-100, and hydroxyapatite. The molecular weight of the enzymes were estimated by the elution volumes from a Sephadex G-100 column and were found to be about 43,000 (isoenzyme 1) and 69,000 (isoenzyme 2). Maximum rates of reaction were observed in the case of coniferyl alcohol oxidation at pH 9.2 (Isoenzyme 1) and pH 8.8 (isoenzyme 2); in the reverse reaction pH 6.5 was optimal for isoenzyme 2. Whereas isoenzyme 1 is specific for coniferyl alcohol, isoenzyme 2 can also oxidize cinnamyl alcohol and a number of substituted cinnamyl alcohols, Km values for substituted cinnamaldehydes are 3-11 times lower than for the corresponding alcohols. Neither isoenzyme reacted with benzyl alcohol, anisic alcohol or ethanol. Substrate inhibition for the forward and reverse reaction was found with isoenzyme 2 but not with isoenzyme 1. The equilibrium constant was determined to be about 10(9) in favour of coniferaldehyde reduction. The possible role of the cinnamyl alcohol dehydrogenase in lignin biosynthesis is discussed.", "contents": "Purification and properties of isoenzymes of cinnamyl-alcohol dehydrogenase from soybean-cell-suspension cultures. Two isoenzymes of an NADP+ -dependent cinnamyl alcohol dehydrogenase and an NAD+ - dependent aliphatic alcohol dehydrogenase were extracted from cell suspension cultures of soybean (Glycine max L., var. Mandarin) which form lignin during growth. These enzymes could be separated from each other by chromatography on DEAE-cellulose and hydroxyapatite. The cinnamyl alcohol dehydrogenase isoenzymes were partially purified by (NH4)2SO4 fractionation, and column chromatography on DEAE-cellulose, Sephadex G-100, and hydroxyapatite. The molecular weight of the enzymes were estimated by the elution volumes from a Sephadex G-100 column and were found to be about 43,000 (isoenzyme 1) and 69,000 (isoenzyme 2). Maximum rates of reaction were observed in the case of coniferyl alcohol oxidation at pH 9.2 (Isoenzyme 1) and pH 8.8 (isoenzyme 2); in the reverse reaction pH 6.5 was optimal for isoenzyme 2. Whereas isoenzyme 1 is specific for coniferyl alcohol, isoenzyme 2 can also oxidize cinnamyl alcohol and a number of substituted cinnamyl alcohols, Km values for substituted cinnamaldehydes are 3-11 times lower than for the corresponding alcohols. Neither isoenzyme reacted with benzyl alcohol, anisic alcohol or ethanol. Substrate inhibition for the forward and reverse reaction was found with isoenzyme 2 but not with isoenzyme 1. The equilibrium constant was determined to be about 10(9) in favour of coniferaldehyde reduction. The possible role of the cinnamyl alcohol dehydrogenase in lignin biosynthesis is discussed."}
{"id": "PMID:1251", "title": "The pyruvate-dehydrogenase complex from Azotobacter vinelandii. 2. Regulation of the activity.", "content": "The presence of activators(AMP and sulphate) or inhibitors(acetyl-CoA) has no influence on the Hill coefficient of the S-shaped [pyruvate]--velocity curve of either the pyruvate-NAD+ overall reaction(h equals 2.5) or that of the pyruvate-K3Fe(CN)6 ACTIVITY OF THE FIRST ENZYME (H EQUALs 1.3). pH STUDIES INDICATED THAT THE Hill coefficient is dependent on subunit ionization within the pyruvate-containing complex and not on those in the free complex. It is concluded that pyruvate conversion rather that pyruvate binding is responsible for the allosteric pattern. The activity is due to absence of a protein kinase, mainly regulated at the acetyl-CoA/CoA, and NADH/NAD+ levels and by the value of the energy charge.", "contents": "The pyruvate-dehydrogenase complex from Azotobacter vinelandii. 2. Regulation of the activity. The presence of activators(AMP and sulphate) or inhibitors(acetyl-CoA) has no influence on the Hill coefficient of the S-shaped [pyruvate]--velocity curve of either the pyruvate-NAD+ overall reaction(h equals 2.5) or that of the pyruvate-K3Fe(CN)6 ACTIVITY OF THE FIRST ENZYME (H EQUALs 1.3). pH STUDIES INDICATED THAT THE Hill coefficient is dependent on subunit ionization within the pyruvate-containing complex and not on those in the free complex. It is concluded that pyruvate conversion rather that pyruvate binding is responsible for the allosteric pattern. The activity is due to absence of a protein kinase, mainly regulated at the acetyl-CoA/CoA, and NADH/NAD+ levels and by the value of the energy charge."}
{"id": "PMID:1252", "title": "Arginine decarboxylase from Lathyrus sativus seedlings. Purification and properites.", "content": "Arginine decarboxylase which makes its appearance in Lathyrus sativus seedlings after 24 h of seed germination reaches its highest level around 5-7 days, the cotyledons containing about 60% of the total activity in the seedlings at day 5. The cytosol enzyme was purified 977-fold from whole seedlings by steps involving manganese chloride treatment, ammonium sulphate and acetone fractionations, positive adsorption on alumina C-gamma gel, DEAE-Sephadex chromatography followed by preparative disc gel electrophoresis. The enzyme was shown to be homogeneous by electrophoretic and immunological criteria, had a molecular weight of 220,000 and appears to be a hexamer with identical subunits. The optimal pH and temperature for the enzyme activity were 8.5 and 45 degrees C respectively. The enzyme follows typical Michaelis-Menten kinetics with a Km value of 1.73 mM for arginine. Though Mn2+ at lower concentrations stimulated the enzyme activity, there was no dependence of the enzyme on any metal for the activity. The arginine decarboxylase of L. sativus is a sulfhydryl enzyme. The data on co-factor requirement, inhibition by carbonyl reagents, reducing agents and pyridoxal phosphate inhibitors, and a partial reversal by pyridoxal phosphate of inhibition by pyridoxal-HCl suggests that pyridoxal 5'-phosphate is involved as a co-factor for the enzyme. The enzyme activity was inhibited competitively by various amines including the product agmatine. Highest inhibition was obtained with spermine and arcain. The substrate analogue, L-canavanine, homologue L-homoarginine and other basic amino acids like L-lysine and L-ornithine inhibited the enzyme activity competitively, homoarginine being the most effective in this respect.", "contents": "Arginine decarboxylase from Lathyrus sativus seedlings. Purification and properites. Arginine decarboxylase which makes its appearance in Lathyrus sativus seedlings after 24 h of seed germination reaches its highest level around 5-7 days, the cotyledons containing about 60% of the total activity in the seedlings at day 5. The cytosol enzyme was purified 977-fold from whole seedlings by steps involving manganese chloride treatment, ammonium sulphate and acetone fractionations, positive adsorption on alumina C-gamma gel, DEAE-Sephadex chromatography followed by preparative disc gel electrophoresis. The enzyme was shown to be homogeneous by electrophoretic and immunological criteria, had a molecular weight of 220,000 and appears to be a hexamer with identical subunits. The optimal pH and temperature for the enzyme activity were 8.5 and 45 degrees C respectively. The enzyme follows typical Michaelis-Menten kinetics with a Km value of 1.73 mM for arginine. Though Mn2+ at lower concentrations stimulated the enzyme activity, there was no dependence of the enzyme on any metal for the activity. The arginine decarboxylase of L. sativus is a sulfhydryl enzyme. The data on co-factor requirement, inhibition by carbonyl reagents, reducing agents and pyridoxal phosphate inhibitors, and a partial reversal by pyridoxal phosphate of inhibition by pyridoxal-HCl suggests that pyridoxal 5'-phosphate is involved as a co-factor for the enzyme. The enzyme activity was inhibited competitively by various amines including the product agmatine. Highest inhibition was obtained with spermine and arcain. The substrate analogue, L-canavanine, homologue L-homoarginine and other basic amino acids like L-lysine and L-ornithine inhibited the enzyme activity competitively, homoarginine being the most effective in this respect."}
{"id": "PMID:1253", "title": "Yeast hexokinase A. Succinylation and properties of the active subunit.", "content": "Yeast hexokinase A (ATP:D-hexose 6-phosphotransferase, EC2.7.1.1) dissociates into its subunits upon reaction with succinic anhydride. The chemically modified subunits could be isolated in a catalytically active form. The Km values found for ATP and for glucose were of the some order as those found for the native enzyme. Of the 37 amino groups present per enzyme subunit, 2-3 of these groups might be located in the proximity of the region of subunit interactions. The 50% loss of the initial activity, which follows the succinylation of these more reactive amino groups, does not seem to be due to the modification of a residue on the enzyme active site or to a change of the tertiary structure of the protein. This 50%loss of the enzyme activity may be related to the dissociation of the dimer into monomers. Both native enzyme and the succinylated subunits have the same H-dependent denaturation rate profiles in response to 2 M urea. Moreover, the apparent pK of the group involved in the transition from a more stable conformation of the protein in the acid range to a less stable one at alkaline pH seems to be similar to the pK of the group implicated in the transition between the protonated inactive form of the enzyme and an active deprotonated form. The succinylated subunit presents 'negative co-operativity' with respect to ATP at slightly acid pH; however, the burst-type slow transient in the reaction progress curve and the activation effect induced by physiological polyanions, effects observed for the native enzyme, were not detected in the standard experimental conditions with the succinylated subunit.", "contents": "Yeast hexokinase A. Succinylation and properties of the active subunit. Yeast hexokinase A (ATP:D-hexose 6-phosphotransferase, EC2.7.1.1) dissociates into its subunits upon reaction with succinic anhydride. The chemically modified subunits could be isolated in a catalytically active form. The Km values found for ATP and for glucose were of the some order as those found for the native enzyme. Of the 37 amino groups present per enzyme subunit, 2-3 of these groups might be located in the proximity of the region of subunit interactions. The 50% loss of the initial activity, which follows the succinylation of these more reactive amino groups, does not seem to be due to the modification of a residue on the enzyme active site or to a change of the tertiary structure of the protein. This 50%loss of the enzyme activity may be related to the dissociation of the dimer into monomers. Both native enzyme and the succinylated subunits have the same H-dependent denaturation rate profiles in response to 2 M urea. Moreover, the apparent pK of the group involved in the transition from a more stable conformation of the protein in the acid range to a less stable one at alkaline pH seems to be similar to the pK of the group implicated in the transition between the protonated inactive form of the enzyme and an active deprotonated form. The succinylated subunit presents 'negative co-operativity' with respect to ATP at slightly acid pH; however, the burst-type slow transient in the reaction progress curve and the activation effect induced by physiological polyanions, effects observed for the native enzyme, were not detected in the standard experimental conditions with the succinylated subunit."}
{"id": "PMID:1254", "title": "The renaturation of reduced polyalanyl-chymotrypsinogen and chymotrypsinogen.", "content": "Chymotrypsinogen has been successfully renatured in solution, after reduction of its 5 disulfide bonds in 6 M guanidine-HCl. This has been made possible by the study of the renaturation of a model derivative, polyalanyl-chymotrypsinogen. The reduced derivative is shown to refold and reoxodize spontaneously, with a 30-40% yield, into molecules which are monomeric and fully susceptible to activation by trypsin. Chymotrypsinogen can also be renatured but only in the presence of reagents allowing disulfide interchange and of moderate concentrations of guanidine-HCl or urea. These results illustrate how the kinetic trapping of incorrectly folded molecules by wrong S-S bonds and aggregation can be overcome, thus allowing the correct refolding of the protein.", "contents": "The renaturation of reduced polyalanyl-chymotrypsinogen and chymotrypsinogen. Chymotrypsinogen has been successfully renatured in solution, after reduction of its 5 disulfide bonds in 6 M guanidine-HCl. This has been made possible by the study of the renaturation of a model derivative, polyalanyl-chymotrypsinogen. The reduced derivative is shown to refold and reoxodize spontaneously, with a 30-40% yield, into molecules which are monomeric and fully susceptible to activation by trypsin. Chymotrypsinogen can also be renatured but only in the presence of reagents allowing disulfide interchange and of moderate concentrations of guanidine-HCl or urea. These results illustrate how the kinetic trapping of incorrectly folded molecules by wrong S-S bonds and aggregation can be overcome, thus allowing the correct refolding of the protein."}
{"id": "PMID:1255", "title": "Further studies on lipid-peroxide formation in isolated hepatocytes.", "content": "Lipid peroxide formation was initiated by the addition of either ADP-complexed Fe3+ or cumene hydroperoxide to a suspension of isolated hepatocytes. The reaction was monitored by malonaldehyde measurements. Upon the addition of iron, malonaldehyde production in the cells started immediately but ceased within 30-60 min, and the response was dose-related with iron concentrations ranging from 19 to 187 muM. Malonaldehyde formation was associated with increased oxygen uptake and conjugated diene production. The addition in vitro of N,N,N',N'-tetramethyl-p-phenylenediamine, menadione or p-benzoquinone inhibited the iron-induced malonaldehyde production. It was also possible to demonstrate an apparent disappearance of malonaldehyde from fresh cells by addition of adequate amounts of N,N,N',N'-tetramethyl-p-phenylenediamine (100 muM). The attenuation of the iron-induced malonaldehyde production was found to be correlated with an increased binding of iron to an intracellular ferritin fraction. Further, malonaldehyde formation was also associated with a conversion of reduced glutathione to the oxidized form which, in turn, revealed a faster permeation out of the cells into the surrounding medium of the oxidized than of the reduced thiol. So, concomitant with the redox alterations, there was also an overall loss of glutathione from the cells. Cumene hydroperoxide-induced malonaldehyde production could be initiated by the addition of this peroxide in concentrations ranging from 150 muM to the liver cell incubate. With concentrations below 150 muM, a lag phase was present which seemed to be glutathione-dependent. It is concluded that iron enters the cell, then is probably reduced inside the cell by NADPH via the NADPH-cytochrome P-450 reductase, and in the reduced state initiates lipid peroxidation. The reaction is inhibited by intracellular mechanisms, the glutathione redox system being of principal importance, and possibly terminated by the iron-apoferritin complex formation.", "contents": "Further studies on lipid-peroxide formation in isolated hepatocytes. Lipid peroxide formation was initiated by the addition of either ADP-complexed Fe3+ or cumene hydroperoxide to a suspension of isolated hepatocytes. The reaction was monitored by malonaldehyde measurements. Upon the addition of iron, malonaldehyde production in the cells started immediately but ceased within 30-60 min, and the response was dose-related with iron concentrations ranging from 19 to 187 muM. Malonaldehyde formation was associated with increased oxygen uptake and conjugated diene production. The addition in vitro of N,N,N',N'-tetramethyl-p-phenylenediamine, menadione or p-benzoquinone inhibited the iron-induced malonaldehyde production. It was also possible to demonstrate an apparent disappearance of malonaldehyde from fresh cells by addition of adequate amounts of N,N,N',N'-tetramethyl-p-phenylenediamine (100 muM). The attenuation of the iron-induced malonaldehyde production was found to be correlated with an increased binding of iron to an intracellular ferritin fraction. Further, malonaldehyde formation was also associated with a conversion of reduced glutathione to the oxidized form which, in turn, revealed a faster permeation out of the cells into the surrounding medium of the oxidized than of the reduced thiol. So, concomitant with the redox alterations, there was also an overall loss of glutathione from the cells. Cumene hydroperoxide-induced malonaldehyde production could be initiated by the addition of this peroxide in concentrations ranging from 150 muM to the liver cell incubate. With concentrations below 150 muM, a lag phase was present which seemed to be glutathione-dependent. It is concluded that iron enters the cell, then is probably reduced inside the cell by NADPH via the NADPH-cytochrome P-450 reductase, and in the reduced state initiates lipid peroxidation. The reaction is inhibited by intracellular mechanisms, the glutathione redox system being of principal importance, and possibly terminated by the iron-apoferritin complex formation."}
{"id": "PMID:1256", "title": "On the mechanism of ketogenesis and its control. Purification, kinetic mechanism and regulation of different forms of mitochondrial acetoacetyl-CoA thiolases from ox liver.", "content": "1. Two mitochondrial forms of acetoacetyl-CoA thiolases designated as enzyme A and enzyme B were crystallized from ox liver. They could be shown to be homogenous by polyacrylamide gel electrophoresis. 2. In direction of acetoacetyl-CoA cleavage enzyme A shows a double competitive substrate inhibition when acetoacetyl-CoA is varied at different fixed CoA concentrations. With enzyme B a parallel kinetic pattern is obtained when acetoacetyl-CoA is varied at different fixed CoA concentrations. In direction of acetoacetyl-CoA synthesis both enzymes show linear reciprocal plots of initial velocities against acetyl-CoA concentrations in absence of CoA. These initial velocity kinetics in the forward and in the reverse direction are in accordance with a ping-pong mechanism of reaction for both enzymes involving an acetyl-S-enzyme as intermediate. 3. Under saturating concentrations of substrate, the ratios of acetoacetyl-CoA synthesis/aceto-acetyl-CoA cleavage is 0.31 for enzyme A and 0.08 for enzyme B. The maximum velocity in direction of acetoacetyl-CoA synthesis of enzymes A and B are 0.43 mumol X min-1 X unit thiolase-1 and 0.10 mumol X min-1 X unit thiolase-1, respectively. 4. Both enzymes show nearly the same affinity for acetyl-CoA. The Km values are 91 muM (enzyme A) and 80 muM (enzyme B). 5. Coenzyme A and acetoacetyl-CoA both act as inhibitors in direction of acetoacetyl-CoA synthesis: coenzyme A is a nonlinear competitive inhibitor of both enzymes. Acetoacetyl-CoA exerts a negative cooperativity on enzyme A (nH = 0.63) and is a competitive inhibitor for enzyme B (Ki = 1.6 muM). 6. The catalytic and regulatory properties of the acetoacetyl-CoA thiolases A and B are discussed in terms of their proposed role in regulating ketogenesis. Intracellular fluctuations of acetoacetyl-CoA/3-hydroxybutyryl-CoA ratios, resulting in a suspension of inhibition of both enzymes at high NADH/NAD ratios, are postulated as a control mechanism of ketogenesis in addition to mechanisms already known.", "contents": "On the mechanism of ketogenesis and its control. Purification, kinetic mechanism and regulation of different forms of mitochondrial acetoacetyl-CoA thiolases from ox liver. 1. Two mitochondrial forms of acetoacetyl-CoA thiolases designated as enzyme A and enzyme B were crystallized from ox liver. They could be shown to be homogenous by polyacrylamide gel electrophoresis. 2. In direction of acetoacetyl-CoA cleavage enzyme A shows a double competitive substrate inhibition when acetoacetyl-CoA is varied at different fixed CoA concentrations. With enzyme B a parallel kinetic pattern is obtained when acetoacetyl-CoA is varied at different fixed CoA concentrations. In direction of acetoacetyl-CoA synthesis both enzymes show linear reciprocal plots of initial velocities against acetyl-CoA concentrations in absence of CoA. These initial velocity kinetics in the forward and in the reverse direction are in accordance with a ping-pong mechanism of reaction for both enzymes involving an acetyl-S-enzyme as intermediate. 3. Under saturating concentrations of substrate, the ratios of acetoacetyl-CoA synthesis/aceto-acetyl-CoA cleavage is 0.31 for enzyme A and 0.08 for enzyme B. The maximum velocity in direction of acetoacetyl-CoA synthesis of enzymes A and B are 0.43 mumol X min-1 X unit thiolase-1 and 0.10 mumol X min-1 X unit thiolase-1, respectively. 4. Both enzymes show nearly the same affinity for acetyl-CoA. The Km values are 91 muM (enzyme A) and 80 muM (enzyme B). 5. Coenzyme A and acetoacetyl-CoA both act as inhibitors in direction of acetoacetyl-CoA synthesis: coenzyme A is a nonlinear competitive inhibitor of both enzymes. Acetoacetyl-CoA exerts a negative cooperativity on enzyme A (nH = 0.63) and is a competitive inhibitor for enzyme B (Ki = 1.6 muM). 6. The catalytic and regulatory properties of the acetoacetyl-CoA thiolases A and B are discussed in terms of their proposed role in regulating ketogenesis. Intracellular fluctuations of acetoacetyl-CoA/3-hydroxybutyryl-CoA ratios, resulting in a suspension of inhibition of both enzymes at high NADH/NAD ratios, are postulated as a control mechanism of ketogenesis in addition to mechanisms already known."}
{"id": "PMID:1257", "title": "D-glucose-6-phosphate dehydrogenase (Entner-Doudoroff enzyme) from Pseudomonas fluorescens. Purification, properties and regulation.", "content": "1. The existence of two different D-glucose-6-phosphate dehydrogenases in Pseudomonas fluorescens has been demonstrated. Based on their different specificity and their different metabolic regulation one enzyme is appointed to the Entner-Doudoroff pathway and the other to the hexose monophosphate pathway. 2. A procedure is described for the isolation of that D-glucose-6-phosphate dehydrogenase which forms part of the Entner-Doudoroff pathway (Entner-Doudoroff enzyme). A 950-fold purification was achieved with an overall yield of 44%. The final preparation, having a specific activity of about 300 mumol NADH formed per min per mg protein, was shown to be homogeneous. 3. The molecular weight of the Entner-Doudoroff enzyme has been determined to be 220000 by gel permeation chromatography, and that of the other enzyme (Zwischenferment) has been shown to be 265000. 4. The pI of the Entner-Doudoroff enzyme has been shown to be 5.24 and that of the Zwischenferment 4.27. The Entner-Doudoroff enzyme is stable in the range of pH 6 to 10.5 and shows its maximal activity at pH 8.9. 5. The Entner-Doudoroff enzyme showed specificity for NAD+ as well as for NADP+ and exhibited homotropic effects for D-glucose 6-phosphate. It is inhibited by ATP which acts as a negative allosteric effector. Other nucleoside triphosphates as well as ADP are also inhibitory. 6. The enzyme catalyzes the transfer of the axial hydrogen at carbon-1 of beta-D-glucopyranose 6-phosphate to the si face of carbon-4 of the nicotinamide ring and must be classified as B-side stereospecific dehydrogenase.", "contents": "D-glucose-6-phosphate dehydrogenase (Entner-Doudoroff enzyme) from Pseudomonas fluorescens. Purification, properties and regulation. 1. The existence of two different D-glucose-6-phosphate dehydrogenases in Pseudomonas fluorescens has been demonstrated. Based on their different specificity and their different metabolic regulation one enzyme is appointed to the Entner-Doudoroff pathway and the other to the hexose monophosphate pathway. 2. A procedure is described for the isolation of that D-glucose-6-phosphate dehydrogenase which forms part of the Entner-Doudoroff pathway (Entner-Doudoroff enzyme). A 950-fold purification was achieved with an overall yield of 44%. The final preparation, having a specific activity of about 300 mumol NADH formed per min per mg protein, was shown to be homogeneous. 3. The molecular weight of the Entner-Doudoroff enzyme has been determined to be 220000 by gel permeation chromatography, and that of the other enzyme (Zwischenferment) has been shown to be 265000. 4. The pI of the Entner-Doudoroff enzyme has been shown to be 5.24 and that of the Zwischenferment 4.27. The Entner-Doudoroff enzyme is stable in the range of pH 6 to 10.5 and shows its maximal activity at pH 8.9. 5. The Entner-Doudoroff enzyme showed specificity for NAD+ as well as for NADP+ and exhibited homotropic effects for D-glucose 6-phosphate. It is inhibited by ATP which acts as a negative allosteric effector. Other nucleoside triphosphates as well as ADP are also inhibitory. 6. The enzyme catalyzes the transfer of the axial hydrogen at carbon-1 of beta-D-glucopyranose 6-phosphate to the si face of carbon-4 of the nicotinamide ring and must be classified as B-side stereospecific dehydrogenase."}
{"id": "PMID:1258", "title": "Purification and properties of potato 1,4-alpha-D-glucan:1,4-alpha-D-glucan 6-alpha-(1,4-alpha-glucano)-transferase. Evidence against a dual catalytic function in amylose-branching enzyme.", "content": "Q-Enzyme, the enzyme that synthesizes the 1,6-alpha-glucosidic branch linkages of amylopectin, has been purified from potato to near homogeneity. The molecular weight of the enzyme is 85000. The active enzyme is a monomer, with a molar activity at pH 7.0 and 24 degrees C of 15. The energy of activation is 25 kJ/mol below 15 degrees C, changing sharply to 63 kJ/mol above that temperature. Enzyme activity is not affected by Mg2+ or ATP. There are about 11 readily titratable sulfhydryl groups per molecule. The evidence that the enzyme is a single protein entity, without hydrolytic activity towards amylose, contrasts with an earlier report that Q-enzyme consists of two components, a hydrolase with molecular weight 70000, and a transferase with molecular weight 20000. Q-enzyme acts on native and synthetic amyloses to give products resembling amylopectin in terms of average unit chain length, degress of beta-amylolysis and iodine stain. The profiles of the unit chains of these synthetic products are, however, different from that of native amylopectin. Additional branch linkages are introduced by Q-enzyme into potato amylopectin, but the product bears no resemblance to phytoglycogen.", "contents": "Purification and properties of potato 1,4-alpha-D-glucan:1,4-alpha-D-glucan 6-alpha-(1,4-alpha-glucano)-transferase. Evidence against a dual catalytic function in amylose-branching enzyme. Q-Enzyme, the enzyme that synthesizes the 1,6-alpha-glucosidic branch linkages of amylopectin, has been purified from potato to near homogeneity. The molecular weight of the enzyme is 85000. The active enzyme is a monomer, with a molar activity at pH 7.0 and 24 degrees C of 15. The energy of activation is 25 kJ/mol below 15 degrees C, changing sharply to 63 kJ/mol above that temperature. Enzyme activity is not affected by Mg2+ or ATP. There are about 11 readily titratable sulfhydryl groups per molecule. The evidence that the enzyme is a single protein entity, without hydrolytic activity towards amylose, contrasts with an earlier report that Q-enzyme consists of two components, a hydrolase with molecular weight 70000, and a transferase with molecular weight 20000. Q-enzyme acts on native and synthetic amyloses to give products resembling amylopectin in terms of average unit chain length, degress of beta-amylolysis and iodine stain. The profiles of the unit chains of these synthetic products are, however, different from that of native amylopectin. Additional branch linkages are introduced by Q-enzyme into potato amylopectin, but the product bears no resemblance to phytoglycogen."}
{"id": "PMID:1259", "title": "Factors affecting the molecular structure and the agglutinating ability of concanavalin A and other lectins.", "content": "Ultracentrifugation analyses were performed on lectins under varying conditions of pH, ionic strength and temperature. It has been demonstrated that the phytohemagglutinin from Phaseolus vulgaris, the wheat germ agglutinin and the soybean agglutinin are stable when these parameters are varied, whereas the concanavalin A molecule exhibits a striking reversible dimer-tetramer transition with variation in pH (from 6.0 to 7.2) and temperature (from 4 degrees up to 37 degrees C). It has also been demonstrated that, in agglutination experiments undertaken at different temperatures, cells do eventually aggregate with the first three lectins provided that incubation time is sufficient, whereas the concanavalin-A-induced agglutination was previously found to be temperature-sensitive. These results strongly suggest that the effect of temperature on agglutination by lectins may essentially be due to a structural transition of the lectin itself and nott only to modification of cell surface properties.", "contents": "Factors affecting the molecular structure and the agglutinating ability of concanavalin A and other lectins. Ultracentrifugation analyses were performed on lectins under varying conditions of pH, ionic strength and temperature. It has been demonstrated that the phytohemagglutinin from Phaseolus vulgaris, the wheat germ agglutinin and the soybean agglutinin are stable when these parameters are varied, whereas the concanavalin A molecule exhibits a striking reversible dimer-tetramer transition with variation in pH (from 6.0 to 7.2) and temperature (from 4 degrees up to 37 degrees C). It has also been demonstrated that, in agglutination experiments undertaken at different temperatures, cells do eventually aggregate with the first three lectins provided that incubation time is sufficient, whereas the concanavalin-A-induced agglutination was previously found to be temperature-sensitive. These results strongly suggest that the effect of temperature on agglutination by lectins may essentially be due to a structural transition of the lectin itself and nott only to modification of cell surface properties."}
{"id": "PMID:1260", "title": "Axoplasm chemical composition in Myxicola and solubility properties of its structural proteins.", "content": "The chemical composition of axoplasm extracted from the giant axon of Myxicola infundibulum has been analysed, and some of the factors which disperse its gel structure have been identified. 2. The axoplasm contains about 3-6% protein, and 0-12% lipid. It is isosmotic with sea water and has a pH near 7-0. 3. Inorganic ions in extracted axoplasm include: Na+, 13m-mole/kg wet wtl; K+, 280; Cl-, 24; Ca2+, 0-3; Mg2+, 3. 4. Free organic ions in axoplasm include: gly, 180 m-mole/kg wet st.; cysteic acid, 120; asp, 75; glu, 10; ala, 7; tau, 5; thr, 2; gln and ser, trace; homarine, 63; isethionate, 0. 5. The gel structure is dispersed by solutions containing 1--10 mM-Ca2+, because this ion activates an endogenous protease. The gel can also be dispersed without proteilysis by solutions containing 0-5 M-KCl, or 0-5 M guanidine hydrochloride, or 3-5 M urea, all of which break down neurofilaments. 6. It is argued that many aspects of the composition and dispersal properties of Myxicola axoplasm are similar to those in other axons.", "contents": "Axoplasm chemical composition in Myxicola and solubility properties of its structural proteins. The chemical composition of axoplasm extracted from the giant axon of Myxicola infundibulum has been analysed, and some of the factors which disperse its gel structure have been identified. 2. The axoplasm contains about 3-6% protein, and 0-12% lipid. It is isosmotic with sea water and has a pH near 7-0. 3. Inorganic ions in extracted axoplasm include: Na+, 13m-mole/kg wet wtl; K+, 280; Cl-, 24; Ca2+, 0-3; Mg2+, 3. 4. Free organic ions in axoplasm include: gly, 180 m-mole/kg wet st.; cysteic acid, 120; asp, 75; glu, 10; ala, 7; tau, 5; thr, 2; gln and ser, trace; homarine, 63; isethionate, 0. 5. The gel structure is dispersed by solutions containing 1--10 mM-Ca2+, because this ion activates an endogenous protease. The gel can also be dispersed without proteilysis by solutions containing 0-5 M-KCl, or 0-5 M guanidine hydrochloride, or 3-5 M urea, all of which break down neurofilaments. 6. It is argued that many aspects of the composition and dispersal properties of Myxicola axoplasm are similar to those in other axons."}
{"id": "PMID:1261", "title": "The metabolism of cyclohexanol by Acinetobacter NCIB 9871.", "content": "Acinetobacter NCIB 9871 was isolated by elective culture on cyclohexanol and grows with this compound as sole source of carbon. It displays a restricted growth spectrum, being unable to grow on a wide range of alternative alicyclic alcohols and ketones. Cyclohexanol-grown cells oxidize the growth substrate at a rate of 230 mul of O2/h per mg dry wt with the consumption of 5.65 mumol of O2/mumol substrate. Cyclohexanone is oxidized at a similar rate with the consumption of 4.85 mumol of O2/mumol. 1-Oxa-2-oxocycloheptane and 6-hydroxyhexanoate are both oxidized at the same slow rate of 44 mul of O2/h per mg dry wt and adipate is not oxidized. Studies with cell extracts reveal the presence of inducible dehydrogenases for cyclohexanol, 6-hydroxyhexanoate and 6-oxohexanoate and a monooxygenase, that in conjunction with a lactonase converts cyclohexanone to 6-hydroxyhexanoate. The monooxygenase is therefore presumed to be of the lactone-forming type and the pathway for conversion of cyclohexanol to adipate; cyclohexanol leads to cyclohexanone leads to 1-oxa-2-oxocycloheptane leads to 6-hydroxyhexanoate leads to 6-oxohexanoate leads to adipate; for which key intermediates have been identified chromatographically, is identical with the route for the oxidation of cyclohexanol by Nocardia globerula CL1.", "contents": "The metabolism of cyclohexanol by Acinetobacter NCIB 9871. Acinetobacter NCIB 9871 was isolated by elective culture on cyclohexanol and grows with this compound as sole source of carbon. It displays a restricted growth spectrum, being unable to grow on a wide range of alternative alicyclic alcohols and ketones. Cyclohexanol-grown cells oxidize the growth substrate at a rate of 230 mul of O2/h per mg dry wt with the consumption of 5.65 mumol of O2/mumol substrate. Cyclohexanone is oxidized at a similar rate with the consumption of 4.85 mumol of O2/mumol. 1-Oxa-2-oxocycloheptane and 6-hydroxyhexanoate are both oxidized at the same slow rate of 44 mul of O2/h per mg dry wt and adipate is not oxidized. Studies with cell extracts reveal the presence of inducible dehydrogenases for cyclohexanol, 6-hydroxyhexanoate and 6-oxohexanoate and a monooxygenase, that in conjunction with a lactonase converts cyclohexanone to 6-hydroxyhexanoate. The monooxygenase is therefore presumed to be of the lactone-forming type and the pathway for conversion of cyclohexanol to adipate; cyclohexanol leads to cyclohexanone leads to 1-oxa-2-oxocycloheptane leads to 6-hydroxyhexanoate leads to 6-oxohexanoate leads to adipate; for which key intermediates have been identified chromatographically, is identical with the route for the oxidation of cyclohexanol by Nocardia globerula CL1."}
{"id": "PMID:1262", "title": "Multiple forms of human glutathione S-transferase and their affinity for bilirubin.", "content": "The initial enzymic step in mercapturic acid formation is catalyzed by glutathione S-transferase. Several species of this enzyme, designated as transferases alpha, beta, gamma, delta and epsilon on the basis of increasing isoelectric points, were isolated from human liver. Evidence is presented that each of the purified species is homogeneous with respect to sodium dodecylsulfate-gel electrophoresis. Transferases alpha, beta and epsilon each appear as a single band on gel electrofocusing; transferases gamma and delta are present as two and three bands, respectively, with each band catalytically active. Amino acid analysis indicated the five transferases to be either very closely related or identical in this respect. All enzyme species have a molecular weight of about 48500 and consist of two apparently identical subunits. The spectrum of substrates is the same for each although the enzymes differ slightly in specific activity. As is the case for the rat liver enzymes, each of the human transferases binds bilirubin although this compound is not a substrate.", "contents": "Multiple forms of human glutathione S-transferase and their affinity for bilirubin. The initial enzymic step in mercapturic acid formation is catalyzed by glutathione S-transferase. Several species of this enzyme, designated as transferases alpha, beta, gamma, delta and epsilon on the basis of increasing isoelectric points, were isolated from human liver. Evidence is presented that each of the purified species is homogeneous with respect to sodium dodecylsulfate-gel electrophoresis. Transferases alpha, beta and epsilon each appear as a single band on gel electrofocusing; transferases gamma and delta are present as two and three bands, respectively, with each band catalytically active. Amino acid analysis indicated the five transferases to be either very closely related or identical in this respect. All enzyme species have a molecular weight of about 48500 and consist of two apparently identical subunits. The spectrum of substrates is the same for each although the enzymes differ slightly in specific activity. As is the case for the rat liver enzymes, each of the human transferases binds bilirubin although this compound is not a substrate."}
{"id": "PMID:1263", "title": "Hydrophobic interaction determined by partition in aqueous two-phase systems. Partition of proteins in systems containing fatty-acid esters of poly(ethylene glycol).", "content": "In this report we describe a new method which is useful for measuring hydrophobic interactions between aliphatic hydrocarbon chains and proteins in aqueous environment. The method is based on partition of proteins in an aqueous two-phase system containing dextran and poly(ethylene glycol) and different fatty acid esters of poly(ethylene glycol). The partition is measured under conditions where contributions from electrostatic interactions are eliminated. The difference in partition of proteins in phase systems with and without hyrocarbon groups bound to poly(ethylene glycol), deltalog K, where K is the partition coefficient, is taken as a measure of hydrophobic interaction. Deltalog K varies with size of hydrocarbon chain and type of protein. The length of the aliphatic chain should be greater than 8 carbon atoms in order to get a measurable effect in terms of deltalog K. Bovine serum albumin, beta-lactoglobulin, hemoglobin and myoglobin have been shown to have different affinities for palmitic acid ester of poly(ethylene glycol). No hydrophobic effect could be observed for ovalbumin, cytochrome c or alpha-chymotrypsinogen A.", "contents": "Hydrophobic interaction determined by partition in aqueous two-phase systems. Partition of proteins in systems containing fatty-acid esters of poly(ethylene glycol). In this report we describe a new method which is useful for measuring hydrophobic interactions between aliphatic hydrocarbon chains and proteins in aqueous environment. The method is based on partition of proteins in an aqueous two-phase system containing dextran and poly(ethylene glycol) and different fatty acid esters of poly(ethylene glycol). The partition is measured under conditions where contributions from electrostatic interactions are eliminated. The difference in partition of proteins in phase systems with and without hyrocarbon groups bound to poly(ethylene glycol), deltalog K, where K is the partition coefficient, is taken as a measure of hydrophobic interaction. Deltalog K varies with size of hydrocarbon chain and type of protein. The length of the aliphatic chain should be greater than 8 carbon atoms in order to get a measurable effect in terms of deltalog K. Bovine serum albumin, beta-lactoglobulin, hemoglobin and myoglobin have been shown to have different affinities for palmitic acid ester of poly(ethylene glycol). No hydrophobic effect could be observed for ovalbumin, cytochrome c or alpha-chymotrypsinogen A."}
{"id": "PMID:1264", "title": "Spin-labelled phosphofructokinase. A simple and direct approach to the study of allosteric equilibria under near-physiological conditions.", "content": "Rabbit muscle phosphofructokinase, spin-labelled at its most reactive thiol group, has an electron spin resonance spectrum which is very sensitive to the binding of substrates and allosteric effectors. The spectral changes have been interpreted in terms of a concerted allosteric transition between two conformational states with non-exclusive binding of effectors. On this basis MgATP, fructose 6-phosphate plus ATP, and NH+4ions behave as potent positive effectors, inorganic phosphate, sulphate, AMP, fructose 6-phosphate and fructose 1,6-bisphosphate are less potent activators, and free ATP and H+ions are negative effectors, in agreement with the kinetic behaviour, but citrate behaves anomalously. In addition, the allosteric equilibrium can be displaced towards the inhibited state by selectively modifying two further thiol groups. Strong positive cooperativity occurs under suitable conditions with ATP, metal-ATP and fructose 6-phosphate. Biphasic changes of conformation, attributed to binding at the catalytic and inhibitory sites, have been observed in titrations with ATP. The differentiation of the two ATP binding sites arises in the presence of fructose 6-phosphate because of a distinct concerted effect on conformation between the two substrates at the active site. A similar effect occurs between ATP and citrate. Other heterotropic effects are more consistent with simple models; phosphates favour the binding, and reduce the cooperativity, of fructose 6-phosphate and metal-ATP, whereas excess ATP and H+ ions antagonise the binding and increase the cooperativity of fructose 6-phosphate. The observations are related to existing kinetic and binding studies where possible. Anomalous features of the behaviour suggest that the model should be regarded only as a first approximation.", "contents": "Spin-labelled phosphofructokinase. A simple and direct approach to the study of allosteric equilibria under near-physiological conditions. Rabbit muscle phosphofructokinase, spin-labelled at its most reactive thiol group, has an electron spin resonance spectrum which is very sensitive to the binding of substrates and allosteric effectors. The spectral changes have been interpreted in terms of a concerted allosteric transition between two conformational states with non-exclusive binding of effectors. On this basis MgATP, fructose 6-phosphate plus ATP, and NH+4ions behave as potent positive effectors, inorganic phosphate, sulphate, AMP, fructose 6-phosphate and fructose 1,6-bisphosphate are less potent activators, and free ATP and H+ions are negative effectors, in agreement with the kinetic behaviour, but citrate behaves anomalously. In addition, the allosteric equilibrium can be displaced towards the inhibited state by selectively modifying two further thiol groups. Strong positive cooperativity occurs under suitable conditions with ATP, metal-ATP and fructose 6-phosphate. Biphasic changes of conformation, attributed to binding at the catalytic and inhibitory sites, have been observed in titrations with ATP. The differentiation of the two ATP binding sites arises in the presence of fructose 6-phosphate because of a distinct concerted effect on conformation between the two substrates at the active site. A similar effect occurs between ATP and citrate. Other heterotropic effects are more consistent with simple models; phosphates favour the binding, and reduce the cooperativity, of fructose 6-phosphate and metal-ATP, whereas excess ATP and H+ ions antagonise the binding and increase the cooperativity of fructose 6-phosphate. The observations are related to existing kinetic and binding studies where possible. Anomalous features of the behaviour suggest that the model should be regarded only as a first approximation."}
{"id": "PMID:1265", "title": "Cytochrome c interaction with membranes. Absorption and emission spectra and binding characteristics of iron-free cytochrome c.", "content": "A cytochrome c derivative from which iron is removed has been prepared and characterized. Several lines of evidence indicate that native and porphyrin cytochrome c have similar conformations: they have similar elution characteristics on Sephadex gel chromatography; in both proteins the tryptophan fluorescence is quenched and the pK values of protonation of the porphyrin are identical. Porphyrin cytochrome c does not substitute for native cytochrome c in either the oxidase reaction or in restoring electron transport in cytochrome-c-depleted mitochondria. It does however competitively inhibit native cytochrome c in these reactions, the Ki for inhibition being larger than the Km for reaction. The absorption and emission spectra, and the polarized excitation spectrum of the porphyrin cytochrome c are characteristic of free base porphyrin. The absence of fluorescence quenching of porphyrin cytochrome c  when the protein is bound to cytochrome oxidase suggests that heme to heme distance between these proteins is larger than 0.5 to 0.9 nm depending upon orientation. Binding of the porphyrin cytochrome c to phospholipids or to mitochondria increases the fluorescence polarization of a positively polarized absorption band, which indicates that the bound form of the protein does not rotate freely within the time scale of relaxation from the excited state.", "contents": "Cytochrome c interaction with membranes. Absorption and emission spectra and binding characteristics of iron-free cytochrome c. A cytochrome c derivative from which iron is removed has been prepared and characterized. Several lines of evidence indicate that native and porphyrin cytochrome c have similar conformations: they have similar elution characteristics on Sephadex gel chromatography; in both proteins the tryptophan fluorescence is quenched and the pK values of protonation of the porphyrin are identical. Porphyrin cytochrome c does not substitute for native cytochrome c in either the oxidase reaction or in restoring electron transport in cytochrome-c-depleted mitochondria. It does however competitively inhibit native cytochrome c in these reactions, the Ki for inhibition being larger than the Km for reaction. The absorption and emission spectra, and the polarized excitation spectrum of the porphyrin cytochrome c are characteristic of free base porphyrin. The absence of fluorescence quenching of porphyrin cytochrome c  when the protein is bound to cytochrome oxidase suggests that heme to heme distance between these proteins is larger than 0.5 to 0.9 nm depending upon orientation. Binding of the porphyrin cytochrome c to phospholipids or to mitochondria increases the fluorescence polarization of a positively polarized absorption band, which indicates that the bound form of the protein does not rotate freely within the time scale of relaxation from the excited state."}
{"id": "PMID:1266", "title": "The trypsin and chymotrypsin inhibitors in chick peas (Cicer arietinum L.). Purification and properties of the inhibitors.", "content": "From a crude extract of chick peas (Cicer arietinum L.) inhibitors of trypsin and chymotrypsin were isolated by affinity chromatography on a column of trypsin-Sepharose 6B. The content of inhibitors was found to be 1.5 g/kg. They were further separated into six isoinhibitors by ion-exchange chromatography on DEAE-Sephadex A-25. Two of the isoinhibitors accounted for about 50% of the isolated inhibitors and were further purified to a homogeneous state. The isoinhibitors had a molecular weight of about 10000 as determined by molecular-sieve chromatography on Sephadex G-75. They were stable towards extremes of pH and temperatures up to 75 degrees C or towards digestion by pepsin. They were also stable in 6 M urea but not in 6 M guanidine-HCl. The intact inhibitors were destroyed when the peas were cooked at 100 degrees C or when they were toasted at 130 degrees C. The four major inhibitors had similar amino acid compositions and did not contain detectable amounts of free sulfhydryl groups, tryptophan or carbohydrate. Cysteine is the dominant amino acid residue in all of them and accounted for about 20% of their amino acid content. The isoelectric point of the isoinhibitors lies in the range of pH 4.9-8.6 and two of the major inhibitors had isoelectric points of pH 4.75 and pH 4.96. They inhibited chymotrypsin to the same extent but differed in their inhibitory activities towards trypsin, indicating that they are mixtures of native and trypsinmodified forms and that they probably have separate sites for the two enzymes. They did not inhibit other proteolytic enzymes belonging to two groups (i.e., serine or cysteine enzymes) or originating from different sources (i.e., animals, plants or bacteria).", "contents": "The trypsin and chymotrypsin inhibitors in chick peas (Cicer arietinum L.). Purification and properties of the inhibitors. From a crude extract of chick peas (Cicer arietinum L.) inhibitors of trypsin and chymotrypsin were isolated by affinity chromatography on a column of trypsin-Sepharose 6B. The content of inhibitors was found to be 1.5 g/kg. They were further separated into six isoinhibitors by ion-exchange chromatography on DEAE-Sephadex A-25. Two of the isoinhibitors accounted for about 50% of the isolated inhibitors and were further purified to a homogeneous state. The isoinhibitors had a molecular weight of about 10000 as determined by molecular-sieve chromatography on Sephadex G-75. They were stable towards extremes of pH and temperatures up to 75 degrees C or towards digestion by pepsin. They were also stable in 6 M urea but not in 6 M guanidine-HCl. The intact inhibitors were destroyed when the peas were cooked at 100 degrees C or when they were toasted at 130 degrees C. The four major inhibitors had similar amino acid compositions and did not contain detectable amounts of free sulfhydryl groups, tryptophan or carbohydrate. Cysteine is the dominant amino acid residue in all of them and accounted for about 20% of their amino acid content. The isoelectric point of the isoinhibitors lies in the range of pH 4.9-8.6 and two of the major inhibitors had isoelectric points of pH 4.75 and pH 4.96. They inhibited chymotrypsin to the same extent but differed in their inhibitory activities towards trypsin, indicating that they are mixtures of native and trypsinmodified forms and that they probably have separate sites for the two enzymes. They did not inhibit other proteolytic enzymes belonging to two groups (i.e., serine or cysteine enzymes) or originating from different sources (i.e., animals, plants or bacteria)."}
{"id": "PMID:1267", "title": "Investigations of the structure of 3-methylcrotonyl-CoA carboxylase from Achromobacter.", "content": "It was shown by gel electrophoresis in sodium dodecylsulphate solution that 3-methylcrotonyl-CoA carboxylase from Achromobacter IVS is composed of two different subunits with molecular weights of about 78000 and 96000, respectively. The biotin is bound to the heavier subunit. It was previously found that 3-methylcrotonyl-CoA carboxylase contains four biotin molecules per complex. A complex composed of four of each subunit would thus have a molecular weight of about 700000. This is compatible with the molecular weight of 760000 determined earlier by analytical ultracentrifugation. Both subunits were isolated preparatively. As the subunits, unlike the complex, are very sensitive to oxygen, special precautions had to be taken during isolation. The biotin-containing subunit was isolated by chromatography on DEAE-cellulose in 5 M urea. It no longer catalyzed the overall reaction, yet could still carboxylate free biotin. The biotin-free subunit was separated after dissociation of the enzyme by three-days' dialysis at pH 9.8 under nitrogen. On chromatography over a Sepharose-bound avidin column, the biotin-subunit was fixed and the biotin-free subunit was eluted unretarded. The latter subunit showed no enzymic activity. After the addition of the biotin-containing subunit, overall activity was regenerated. The speed of reassociation is very much enhanced by 3-methylcrotonyl-CoA. It was shown by reassociation experiments under different conditions that probably an initial complex, AxBy is formed, possessing a binding site for 3-methylcrotonyl-CoA. Upon the binding of this substrate the conformation may be changed to a form favourable for reconstitution. Finally, the structures of biotin enzymes from different sources are compared. In the course of evolution there is a tendency toward integration of the different constituent proteins into only one polypeptide chain.", "contents": "Investigations of the structure of 3-methylcrotonyl-CoA carboxylase from Achromobacter. It was shown by gel electrophoresis in sodium dodecylsulphate solution that 3-methylcrotonyl-CoA carboxylase from Achromobacter IVS is composed of two different subunits with molecular weights of about 78000 and 96000, respectively. The biotin is bound to the heavier subunit. It was previously found that 3-methylcrotonyl-CoA carboxylase contains four biotin molecules per complex. A complex composed of four of each subunit would thus have a molecular weight of about 700000. This is compatible with the molecular weight of 760000 determined earlier by analytical ultracentrifugation. Both subunits were isolated preparatively. As the subunits, unlike the complex, are very sensitive to oxygen, special precautions had to be taken during isolation. The biotin-containing subunit was isolated by chromatography on DEAE-cellulose in 5 M urea. It no longer catalyzed the overall reaction, yet could still carboxylate free biotin. The biotin-free subunit was separated after dissociation of the enzyme by three-days' dialysis at pH 9.8 under nitrogen. On chromatography over a Sepharose-bound avidin column, the biotin-subunit was fixed and the biotin-free subunit was eluted unretarded. The latter subunit showed no enzymic activity. After the addition of the biotin-containing subunit, overall activity was regenerated. The speed of reassociation is very much enhanced by 3-methylcrotonyl-CoA. It was shown by reassociation experiments under different conditions that probably an initial complex, AxBy is formed, possessing a binding site for 3-methylcrotonyl-CoA. Upon the binding of this substrate the conformation may be changed to a form favourable for reconstitution. Finally, the structures of biotin enzymes from different sources are compared. In the course of evolution there is a tendency toward integration of the different constituent proteins into only one polypeptide chain."}
{"id": "PMID:1268", "title": "Polyadenylated RNA from Vicia faba meristematic root cells. Localization and size estimation of the poly (A) segment.", "content": "After incubating root apices from two-day-old bean seedlings with [3H] adenine the RNA was extracted from whole cells or polysomes, and the poly (A) sequences were isolated by nuclease digestion followed by poly(U)-Sepharose chromatography. The alterations of the RNA molecules due to the various treatments were monitored by sucrose density gradients. It was found that sequential extraction first at pH 7.6 then at pH 9.0 did not result in a separation between RNA poor in poly(A) sequences and poly(A)-rich RNA. Furthermore chromatography analysis of hydrolysates from nuclease-resistant RNA extracted either at pH 7.6 or pH 9.0 revealed that AMP constituted nearly 95% of the bases and that the poly(A) sequences, about 200 bases, were located at the 3' terminus of the polyadenylated RNA. No size difference was found for the poly(A) segment between the pH-7.6-extracted RNA and that extracted at pH 9.0.", "contents": "Polyadenylated RNA from Vicia faba meristematic root cells. Localization and size estimation of the poly (A) segment. After incubating root apices from two-day-old bean seedlings with [3H] adenine the RNA was extracted from whole cells or polysomes, and the poly (A) sequences were isolated by nuclease digestion followed by poly(U)-Sepharose chromatography. The alterations of the RNA molecules due to the various treatments were monitored by sucrose density gradients. It was found that sequential extraction first at pH 7.6 then at pH 9.0 did not result in a separation between RNA poor in poly(A) sequences and poly(A)-rich RNA. Furthermore chromatography analysis of hydrolysates from nuclease-resistant RNA extracted either at pH 7.6 or pH 9.0 revealed that AMP constituted nearly 95% of the bases and that the poly(A) sequences, about 200 bases, were located at the 3' terminus of the polyadenylated RNA. No size difference was found for the poly(A) segment between the pH-7.6-extracted RNA and that extracted at pH 9.0."}
{"id": "PMID:1269", "title": "Time-dependent inhibition of diamine oxidase by carbonyl-group reagents and urea.", "content": "1. The behaviour of several carbonyl group reagents and urea as time-dependent inhibitors of both pig kidney and human placental diamine oxidase is described. 2. Plots of log (vt/vo) against time were not linear with these reagents as the usual theories predict. 3. This was particularly the case with aminoguanidine and phenylhydrazine and a thorough study of the effects of these compounds on the human placental diamine oxidase is described. 4. By applying a new theory for time-dependent inhibition, the inhibition of diamine oxidase by aminoguanidine and phenylhydrazine is adequately accounted for. 5. The time-dependent recovery of activity on addition of sodium pyruvate suggested that the compounds used are acting solely as carbonyl group reagents, inhibiting by Schiff-base formation at the active-site carbonyl group.", "contents": "Time-dependent inhibition of diamine oxidase by carbonyl-group reagents and urea. 1. The behaviour of several carbonyl group reagents and urea as time-dependent inhibitors of both pig kidney and human placental diamine oxidase is described. 2. Plots of log (vt/vo) against time were not linear with these reagents as the usual theories predict. 3. This was particularly the case with aminoguanidine and phenylhydrazine and a thorough study of the effects of these compounds on the human placental diamine oxidase is described. 4. By applying a new theory for time-dependent inhibition, the inhibition of diamine oxidase by aminoguanidine and phenylhydrazine is adequately accounted for. 5. The time-dependent recovery of activity on addition of sodium pyruvate suggested that the compounds used are acting solely as carbonyl group reagents, inhibiting by Schiff-base formation at the active-site carbonyl group."}
{"id": "PMID:1270", "title": "Acetylglucagon: preparation and characterization.", "content": "Acetylated derivatives of glucagon have been prepared by reacting this hormone under various conditions with acetic anhydride. They have been chemically characterized by the use of a 14C-labeled reagent, by peptide mapping techniques following hydrolysis by pronase and chymotrypsin, and by spectroscopy. Acetylation in sodium acetate (pH 5.5) results in a full substitution of the alpha-amino group of the N-terminal histidyl residue, but in a partial (about 0.3 acetyl group per residue) substitution of the epsilon-amino group of the lysyl residue 12. The monosubstituted (on the alpha-amino group) and the disubstituted (on both amino groups) acetylated components have been separated by chromatography on DEAE-cellulose and CM-cellulose. Acetylation in sodium bicarbonate (pH 8.0) results in a complete substitution of both amino groups and of the hydroxyl groups of the tyrosyl residues 10 and 13. Complete deacetylation of the O-acetyltyrosyl residues occurs upon treatment with hydroxyl-amine. Mono, di and tetraacetylglucagon are homogeneous when analyzed by disc gel electrophoresis; di and tetrasubstituted derivatives show an increased mobility towards the anode. 125I-labeled derivatives of acetylglucagon show higher distribution coefficients in the aqueous two-phase dextran/poly(ethylene glycol) system than do similar derivatives of glucagon. Acetylation decreases in parallel the ability of glucagon to stimulate the activity of adenylate cyclase and to bind to its receptors in liver cell membranes of the rat. The biological potencies of the mono, di and tetrasubstituted derivates are, respectively, about 10, 1 and 0.1% that of native glucagon. The binding properties of the material dissociated from the acetylglucagon-receptor complex suggest that the reduction in biological activity results from a decrease in the intrinsic affinity of the modified glucagon for the receptors, as well as from the presence of small amounts of residual, unreacted glucagon. Studies with 125I-labeled derivatives of glucagon indicate that acetylation decreases the rate of association and increases the rate of dissociation of the hormone-receptor complex.", "contents": "Acetylglucagon: preparation and characterization. Acetylated derivatives of glucagon have been prepared by reacting this hormone under various conditions with acetic anhydride. They have been chemically characterized by the use of a 14C-labeled reagent, by peptide mapping techniques following hydrolysis by pronase and chymotrypsin, and by spectroscopy. Acetylation in sodium acetate (pH 5.5) results in a full substitution of the alpha-amino group of the N-terminal histidyl residue, but in a partial (about 0.3 acetyl group per residue) substitution of the epsilon-amino group of the lysyl residue 12. The monosubstituted (on the alpha-amino group) and the disubstituted (on both amino groups) acetylated components have been separated by chromatography on DEAE-cellulose and CM-cellulose. Acetylation in sodium bicarbonate (pH 8.0) results in a complete substitution of both amino groups and of the hydroxyl groups of the tyrosyl residues 10 and 13. Complete deacetylation of the O-acetyltyrosyl residues occurs upon treatment with hydroxyl-amine. Mono, di and tetraacetylglucagon are homogeneous when analyzed by disc gel electrophoresis; di and tetrasubstituted derivatives show an increased mobility towards the anode. 125I-labeled derivatives of acetylglucagon show higher distribution coefficients in the aqueous two-phase dextran/poly(ethylene glycol) system than do similar derivatives of glucagon. Acetylation decreases in parallel the ability of glucagon to stimulate the activity of adenylate cyclase and to bind to its receptors in liver cell membranes of the rat. The biological potencies of the mono, di and tetrasubstituted derivates are, respectively, about 10, 1 and 0.1% that of native glucagon. The binding properties of the material dissociated from the acetylglucagon-receptor complex suggest that the reduction in biological activity results from a decrease in the intrinsic affinity of the modified glucagon for the receptors, as well as from the presence of small amounts of residual, unreacted glucagon. Studies with 125I-labeled derivatives of glucagon indicate that acetylation decreases the rate of association and increases the rate of dissociation of the hormone-receptor complex."}
{"id": "PMID:1271", "title": "Purification and properties of a periplasmic aminoendopeptidase from Escherichia coli.", "content": "A periplasmic aminoendopeptidase from Escherichia coli has been purified to hemogeneity. It is a monomer of molecular weight 45000 and containing one -- SH group that is necessary for catalytic activity. The study of its substrate specificity indicated that the enzyme has both aminopeptidase and endopeptidase activity. The pH optimum for L-alanine p-nitroanilide hydrolysis is between 7 and 7.5 and that for 125I-labeled casein proteolysis between 7.3 and 7.6. The activation energy for the hydrolysis of L-anine p-nitroanilide was calculated to be 5.3 kcal X mol-1 (22.2 kJ X mol-1).", "contents": "Purification and properties of a periplasmic aminoendopeptidase from Escherichia coli. A periplasmic aminoendopeptidase from Escherichia coli has been purified to hemogeneity. It is a monomer of molecular weight 45000 and containing one -- SH group that is necessary for catalytic activity. The study of its substrate specificity indicated that the enzyme has both aminopeptidase and endopeptidase activity. The pH optimum for L-alanine p-nitroanilide hydrolysis is between 7 and 7.5 and that for 125I-labeled casein proteolysis between 7.3 and 7.6. The activation energy for the hydrolysis of L-anine p-nitroanilide was calculated to be 5.3 kcal X mol-1 (22.2 kJ X mol-1)."}
{"id": "PMID:1272", "title": "The interaction of organic phosphates with human and chicken hemoglobin.", "content": "In this study of the binding properties of inositol hexaphosphate and 2,3-bisphosphoglycerate to chicken and human deoxyhemoglobin and carboxyhemoglobin were compared. It appeared that in all cases the binding to chicken hemoglobin is much stronger than to human hemoglobin. This is very probably due to the fact that 4 out of the 12 residues, responsible for the binding of phosphates in chicken hemoglobin, are arginines. These are absent in human hemoglobin, where the binding site is made up to only 8 residues. For chicken hemoglobin one strong binding site could be observed in both unliganded and liganded hemoglobin. From these observations we conclude that the same binding site is involved in both the oxy- and deoxy structure showing different affinity to phosphates in the two conformational states. For human hemoglobin we reached the same conclusion.", "contents": "The interaction of organic phosphates with human and chicken hemoglobin. In this study of the binding properties of inositol hexaphosphate and 2,3-bisphosphoglycerate to chicken and human deoxyhemoglobin and carboxyhemoglobin were compared. It appeared that in all cases the binding to chicken hemoglobin is much stronger than to human hemoglobin. This is very probably due to the fact that 4 out of the 12 residues, responsible for the binding of phosphates in chicken hemoglobin, are arginines. These are absent in human hemoglobin, where the binding site is made up to only 8 residues. For chicken hemoglobin one strong binding site could be observed in both unliganded and liganded hemoglobin. From these observations we conclude that the same binding site is involved in both the oxy- and deoxy structure showing different affinity to phosphates in the two conformational states. For human hemoglobin we reached the same conclusion."}
{"id": "PMID:1273", "title": "Hepatic nucleases. Extrahepatic origin and association of neutral liver ribonuclease with lysosomes.", "content": "In the large granule fraction of rat liver, the density distribution of inhibitor-sensitive neutral ribonuclease is similar to that for acid hydrolases and its density distribution is similarly modified by Triton WR-1339 accumulation in lysosomes. Particulate neutral ribonuclease is latent; the enzyme is unmasked by very low digitonin concentrations or hypoosmotic shock. These observations demonstrate that the bulk of liver neutral ribonuclease is associated with the lysosomal system. In view of the neutral pH optimum of the enzyme and of some particularities of its distribution in fractionation experiments, the possiblilty of an extrahepatic origin of neutral ribonuclease has been investigated. After partial pancreatectomy, a significant decrease is observed in both plasma and liver neutral ribonuclease. The effect is specific, for it does not occur for other lysosomal enzymes. Also, labelled bovine pancreatic ribonuclease, when injected intravenously, is taken up by the liver. The sedimentable labelled enzyme has a density distribution similar to the distribution of other foreign proteins, horseradish peroxidase or yeast invertase. These results are explained by the uptake of plasmatic neutral ribonuclease from pancreatic origin by the liver.", "contents": "Hepatic nucleases. Extrahepatic origin and association of neutral liver ribonuclease with lysosomes. In the large granule fraction of rat liver, the density distribution of inhibitor-sensitive neutral ribonuclease is similar to that for acid hydrolases and its density distribution is similarly modified by Triton WR-1339 accumulation in lysosomes. Particulate neutral ribonuclease is latent; the enzyme is unmasked by very low digitonin concentrations or hypoosmotic shock. These observations demonstrate that the bulk of liver neutral ribonuclease is associated with the lysosomal system. In view of the neutral pH optimum of the enzyme and of some particularities of its distribution in fractionation experiments, the possiblilty of an extrahepatic origin of neutral ribonuclease has been investigated. After partial pancreatectomy, a significant decrease is observed in both plasma and liver neutral ribonuclease. The effect is specific, for it does not occur for other lysosomal enzymes. Also, labelled bovine pancreatic ribonuclease, when injected intravenously, is taken up by the liver. The sedimentable labelled enzyme has a density distribution similar to the distribution of other foreign proteins, horseradish peroxidase or yeast invertase. These results are explained by the uptake of plasmatic neutral ribonuclease from pancreatic origin by the liver."}
{"id": "PMID:1274", "title": "Glutathione reductase from human erythrocytes. Molecular weight, subunit composition and aggregation properties.", "content": "Glutathione reductase from human erythrocytes exists predominatly as an entity of 100 000 molecular weight under various conditions of pH and ionic strength. The S20,W of 5.5 S and D20W of 50 mum2/s correlate with the molecular weight determined by sedimentation equilibrium. The homogeneity of this species is primarily dependent on the presence of thiols and secondarily on high concentrations of salt. The amino-acid composition of the enzyme shows similarities both with glutathione reductases from other sources and with lipoamide dehydrogenase. From the flavin content and dodecylsulphate-polyacrylamide electrophoresis it is inferred that the native enzyme is a dimer composed of similar subunits of 50 000 molecular weight. In the absence of thiols, glutathione reductase shows a tendency to form tetramers and larger aggregates. Although these larger species are also catalytically active, under cellular conditions the presence of its product, reduced glutathione, should maintain the enzyme as the dimeric entity.", "contents": "Glutathione reductase from human erythrocytes. Molecular weight, subunit composition and aggregation properties. Glutathione reductase from human erythrocytes exists predominatly as an entity of 100 000 molecular weight under various conditions of pH and ionic strength. The S20,W of 5.5 S and D20W of 50 mum2/s correlate with the molecular weight determined by sedimentation equilibrium. The homogeneity of this species is primarily dependent on the presence of thiols and secondarily on high concentrations of salt. The amino-acid composition of the enzyme shows similarities both with glutathione reductases from other sources and with lipoamide dehydrogenase. From the flavin content and dodecylsulphate-polyacrylamide electrophoresis it is inferred that the native enzyme is a dimer composed of similar subunits of 50 000 molecular weight. In the absence of thiols, glutathione reductase shows a tendency to form tetramers and larger aggregates. Although these larger species are also catalytically active, under cellular conditions the presence of its product, reduced glutathione, should maintain the enzyme as the dimeric entity."}
{"id": "PMID:1275", "title": "GAMMA-Glutamyl transpeptidase of sheep-kidney cortex. Isolation, catalytic properties and dissociation into two polypeptide chains.", "content": "Gamma-Glutamyl transpeptidase was isolated from sheep kidney cortex as an apparently homogeneous, highly active protein. At optimal pH and in the absence of acceptors, the enzyme catalyzes the release of about 510 mumol of p-nitroaniline per mg protein per min from the model substrate L-gamma-glutamyl-p-nitroanilide. Polyacrylamide gel electrophoresis in a sodium dodecylsulfate buffer system showed the presence of a large (Mr approximately 65000) and a small (Mr approximately 27000) polypeptide chain. Dissociation into two polypeptide chains was also achieved in 8 M urea. Amidination with dimethylsuberimidate produced a crosslinked protein of molecular weight approximately 90000. In the course of this work a convenient procedure was developed for the determination of gamma-glutamyl transpeptidase activity using L[glycine-2-3H]glutathione as the substrate. In this procedure the release of cysteinyl-[2-3H]glycine from glutathione is followed, after separation of the radioactive di-peptide from unreacted glutathione on a small Dowex-1 acetate column. The reactions with gamma-glutamyl-p-nitroanilide and glutathione are both strongly activated by several metal ions (Ca2+, Mg2+, Na+ and K+) and by a number of amino acids and peptide acceptors. The products of the reaction with glutathione were identified as cysteinylglycine, gamma-glutamylglutathione and glutamate. The formation of these products is consistent with the function of gamma-glutamyl transpeptidase in both the gamma-glutamyl transfer reaction and in the hydrolysis of the gamma-glutamyl bond. The activating effect of metal ions in the reaction with glutathione was shown to be dependent on the acceleration of the transfer reaction; the rate of hydrolysis of the gamma-glutamyl bond remaining unchanged.", "contents": "GAMMA-Glutamyl transpeptidase of sheep-kidney cortex. Isolation, catalytic properties and dissociation into two polypeptide chains. Gamma-Glutamyl transpeptidase was isolated from sheep kidney cortex as an apparently homogeneous, highly active protein. At optimal pH and in the absence of acceptors, the enzyme catalyzes the release of about 510 mumol of p-nitroaniline per mg protein per min from the model substrate L-gamma-glutamyl-p-nitroanilide. Polyacrylamide gel electrophoresis in a sodium dodecylsulfate buffer system showed the presence of a large (Mr approximately 65000) and a small (Mr approximately 27000) polypeptide chain. Dissociation into two polypeptide chains was also achieved in 8 M urea. Amidination with dimethylsuberimidate produced a crosslinked protein of molecular weight approximately 90000. In the course of this work a convenient procedure was developed for the determination of gamma-glutamyl transpeptidase activity using L[glycine-2-3H]glutathione as the substrate. In this procedure the release of cysteinyl-[2-3H]glycine from glutathione is followed, after separation of the radioactive di-peptide from unreacted glutathione on a small Dowex-1 acetate column. The reactions with gamma-glutamyl-p-nitroanilide and glutathione are both strongly activated by several metal ions (Ca2+, Mg2+, Na+ and K+) and by a number of amino acids and peptide acceptors. The products of the reaction with glutathione were identified as cysteinylglycine, gamma-glutamylglutathione and glutamate. The formation of these products is consistent with the function of gamma-glutamyl transpeptidase in both the gamma-glutamyl transfer reaction and in the hydrolysis of the gamma-glutamyl bond. The activating effect of metal ions in the reaction with glutathione was shown to be dependent on the acceleration of the transfer reaction; the rate of hydrolysis of the gamma-glutamyl bond remaining unchanged."}
{"id": "PMID:1276", "title": "Pyrophosphatase and glucuronosyltransferase in microsomal UDPglucuronic-acid metabolism in the rat liver.", "content": "1. A radiochemical method for the studies on the microsomal UDPglucuronic acid metabolism has been developed. 2. The rat liver microsomes caused a rapid hydrolysis of UDPglucuronic acid to D-glucuronic acid 1-phosphate and further although much slower to free D-glucuronic acid. In Tris-HCl buffer (pH 7.4) they were produced in ratio 72 : 1. No other metabolites were found in measurable amounts. The pyrophosphatase splitting UDPglucuronic acid showed a pH optimum at 8.9, but the liberation of D-glucuronic acid from UDPglucuronic acid had two pH maxima (pH 3.5 and 8.5). EDTA appeared to be less powerful inhibitor of pyrophosphatase than previously suggested. About 25 per cent of the UDPglucuronic acid hydrolyzing activity was still remaining in the presence of 10 mM EDTA. D-Glucaro-1,4-lactone was found to have a slight inhibitory action on the pyrophosphatase activity. Citrate inhibited powerfully the hydrolysis of UDPglucuronic acid and the liberation of free D-glucuronic acid. Phosphate was also inhibitory. 3. In the presence of an exogenous UDPglucuronosyltransferase substrate, 4-nitrophenol, the formation of D-glucuronic acid 1-phosphate and free D-glucuronic acid were slightly reduced, and D-glucuronic acid 1-phosphate, 4-nitrophenylglucuronide and free D-glucuronic acid were produced in ratio 78 : 23 : 1. When 10 mM EDTA was added to diminish the hydrolytic consumption of the glucuronyl donor substrate, the corresponding ratio was still as unfavorable as 19 : 2.6 : 1. The measurable activity of UDPglucuronosyltransferase was lower in the presence of phosphate or citrate than in Tris-HCl buffer, although they protected the glucuronyl donor substrate against hydrolysis. 4. The results indicate that even in the presence of added glucuronyl acceptor substrate the hydrolysis of UDPglucuronic acid predominates the conjugation in rat liver microsomes. The rate of the hydrolysis of UDPglucuronic acid is quite considerable even in the presence of EDTA, and it is recommended to control the UDPglucuronic acid pyrophosphatase activity when UDPglucuronosyltransferase and glucuronidation reactions are studied. Free D-glucuronic acid appears to be produced from UDPglucuronic acid for further use via D-glucuronic acid 1-phosphate, the rate-limiting step being the hydrolysis of this intermediate. UDP-glucuronosyltransferase, glucuronides of either endogenous or exogenous aglycones and beta-glucuronidase have only a minor role in this respect in rat liver microsomes.", "contents": "Pyrophosphatase and glucuronosyltransferase in microsomal UDPglucuronic-acid metabolism in the rat liver. 1. A radiochemical method for the studies on the microsomal UDPglucuronic acid metabolism has been developed. 2. The rat liver microsomes caused a rapid hydrolysis of UDPglucuronic acid to D-glucuronic acid 1-phosphate and further although much slower to free D-glucuronic acid. In Tris-HCl buffer (pH 7.4) they were produced in ratio 72 : 1. No other metabolites were found in measurable amounts. The pyrophosphatase splitting UDPglucuronic acid showed a pH optimum at 8.9, but the liberation of D-glucuronic acid from UDPglucuronic acid had two pH maxima (pH 3.5 and 8.5). EDTA appeared to be less powerful inhibitor of pyrophosphatase than previously suggested. About 25 per cent of the UDPglucuronic acid hydrolyzing activity was still remaining in the presence of 10 mM EDTA. D-Glucaro-1,4-lactone was found to have a slight inhibitory action on the pyrophosphatase activity. Citrate inhibited powerfully the hydrolysis of UDPglucuronic acid and the liberation of free D-glucuronic acid. Phosphate was also inhibitory. 3. In the presence of an exogenous UDPglucuronosyltransferase substrate, 4-nitrophenol, the formation of D-glucuronic acid 1-phosphate and free D-glucuronic acid were slightly reduced, and D-glucuronic acid 1-phosphate, 4-nitrophenylglucuronide and free D-glucuronic acid were produced in ratio 78 : 23 : 1. When 10 mM EDTA was added to diminish the hydrolytic consumption of the glucuronyl donor substrate, the corresponding ratio was still as unfavorable as 19 : 2.6 : 1. The measurable activity of UDPglucuronosyltransferase was lower in the presence of phosphate or citrate than in Tris-HCl buffer, although they protected the glucuronyl donor substrate against hydrolysis. 4. The results indicate that even in the presence of added glucuronyl acceptor substrate the hydrolysis of UDPglucuronic acid predominates the conjugation in rat liver microsomes. The rate of the hydrolysis of UDPglucuronic acid is quite considerable even in the presence of EDTA, and it is recommended to control the UDPglucuronic acid pyrophosphatase activity when UDPglucuronosyltransferase and glucuronidation reactions are studied. Free D-glucuronic acid appears to be produced from UDPglucuronic acid for further use via D-glucuronic acid 1-phosphate, the rate-limiting step being the hydrolysis of this intermediate. UDP-glucuronosyltransferase, glucuronides of either endogenous or exogenous aglycones and beta-glucuronidase have only a minor role in this respect in rat liver microsomes."}
{"id": "PMID:1278", "title": "Incorporation of (1-14C)palmitoyl-CoA into phosphatidylcholine by plasma membranes of rat submaxillary glands in vitro.", "content": "1. On incubation with the isolated rat submaxillary gland plasma membranes, [1-14C]palmitoyl-CoA was incorporated mainly into phosphatidylcholine and hydrolysed to [1-14C]palmitic acid and CoASH. 2. The addition of lysophosphatidylcholine enhanced the incorporation into phosphatidylcholine and lowered the hydrolysis of palmitoyl-CoA markedly. 3. In the presence of lysophosphatidylcholine, palmitoyl-CoA incorporation into phosphatidylcholine was maximum at 0.1 mM palmitoyl-CoA, 0.5 mM lysophosphatidylcholine and between pH 7.0 and 9.0. 4. The incorporation into phosphatidylcholine was stimulated by Na+, K+ and K-, inhibited by Ca2+ and Mg2+ and unaffected by sodium deoxycholate and ATP. 5. Epinephrine inhibited the incorporation of palmitoyl-CoA into phosphatidylcholine in the presence or absence of ATP, the inhibition being more in the presence of ATP than in its absence. Dibutyryl adenosine 3':5'-monophosphate mimicked the inhibitory effect of epinephrine.", "contents": "Incorporation of (1-14C)palmitoyl-CoA into phosphatidylcholine by plasma membranes of rat submaxillary glands in vitro. 1. On incubation with the isolated rat submaxillary gland plasma membranes, [1-14C]palmitoyl-CoA was incorporated mainly into phosphatidylcholine and hydrolysed to [1-14C]palmitic acid and CoASH. 2. The addition of lysophosphatidylcholine enhanced the incorporation into phosphatidylcholine and lowered the hydrolysis of palmitoyl-CoA markedly. 3. In the presence of lysophosphatidylcholine, palmitoyl-CoA incorporation into phosphatidylcholine was maximum at 0.1 mM palmitoyl-CoA, 0.5 mM lysophosphatidylcholine and between pH 7.0 and 9.0. 4. The incorporation into phosphatidylcholine was stimulated by Na+, K+ and K-, inhibited by Ca2+ and Mg2+ and unaffected by sodium deoxycholate and ATP. 5. Epinephrine inhibited the incorporation of palmitoyl-CoA into phosphatidylcholine in the presence or absence of ATP, the inhibition being more in the presence of ATP than in its absence. Dibutyryl adenosine 3':5'-monophosphate mimicked the inhibitory effect of epinephrine."}
{"id": "PMID:1279", "title": "Hydrogen-isotope exchange of oxidized and reduced cytochrome c. A comparison of mass spectrometry and infrared methods.", "content": "Hydrogen-deuterium exchange in 2H20 solutions of the two redox states of horse heart cytochrome c was investigated at 20 degrees C, pH 7, by mass spectrometry and infrared spectroscopy. Mass spectrometry indicates that ferricytochrome has 20 hydrogens unexchanged after 24 h, 28 hydrogens exchanging between 10 min and 24 h, and 156 hydrogens exchanging within 10 min; comparative values for ferrocytochrome are 45, 19 and 140. The displacement of the exchange curves obtained by infrared corresponds to 8 to 9 peptide hydrogens. These combined methods show many non-peptide hydrogens exchanging rapidly (87 and 79 for ferricytochrome c and ferrocytochrome c respectively), whereas others, probably buried inside the molecule and involved in hydrogen bonds, are not exchanged, even after 24 h (14 and 30 hydrogens respectively, which is relatively large for a small protein). Infrared results are given in terms of changes of standard free energy for the transconformational reaction which exposes the peptide hydrogens to solvent: in ferricytochrome c and ferrycoytochrome c, 30% and 40% respectively of the peptide hydrogens are protected by conformational transitions stabilized by more than 5 kcal/mol (21 kJ/mol), which implies a large increase in rigidity for the reduced form.", "contents": "Hydrogen-isotope exchange of oxidized and reduced cytochrome c. A comparison of mass spectrometry and infrared methods. Hydrogen-deuterium exchange in 2H20 solutions of the two redox states of horse heart cytochrome c was investigated at 20 degrees C, pH 7, by mass spectrometry and infrared spectroscopy. Mass spectrometry indicates that ferricytochrome has 20 hydrogens unexchanged after 24 h, 28 hydrogens exchanging between 10 min and 24 h, and 156 hydrogens exchanging within 10 min; comparative values for ferrocytochrome are 45, 19 and 140. The displacement of the exchange curves obtained by infrared corresponds to 8 to 9 peptide hydrogens. These combined methods show many non-peptide hydrogens exchanging rapidly (87 and 79 for ferricytochrome c and ferrocytochrome c respectively), whereas others, probably buried inside the molecule and involved in hydrogen bonds, are not exchanged, even after 24 h (14 and 30 hydrogens respectively, which is relatively large for a small protein). Infrared results are given in terms of changes of standard free energy for the transconformational reaction which exposes the peptide hydrogens to solvent: in ferricytochrome c and ferrycoytochrome c, 30% and 40% respectively of the peptide hydrogens are protected by conformational transitions stabilized by more than 5 kcal/mol (21 kJ/mol), which implies a large increase in rigidity for the reduced form."}
{"id": "PMID:1280", "title": "Bacterial metabolism of resorcinylic compounds: purification and properties of orcinol hydroxylase and resorcinol hydroxylase from Pseudomonas putida ORC.", "content": "The hydroxylase activities observed in extracts of Pseudomonas putida ORC after growth on orcinol and resorcinol as sole source of carbon have been purified to homogeneity. Both enzymes were shown to be flavoproteins and to contain approximately 1 mol of FAD for each polypeptide chain, S20,W values for each enzyme are 4.1 +/- 0.1 and are independent of the presence of their aromatic substrates. Molecular weight determinations under native (approximately 68000) and denaturing (approximately 70000) conditions indicated that they are monomeric. The visible absorption spectra identical but the circular dichroic spectra of the two proteins can be distinguished. Although each protein catalyzes the NAD(P)H and O2-dependent hydroxylation of both orcinol and resorcinol, the efficiency of the transformations of the substrates by the two enzymes is radically different; furthermore resorcinol hydroxylase is much more versatile in the aromatic compounds it can utilize as substrates and effectors. Other properties of the enzymes which clearly establish their own identity include their serological characteristics and amino acid composition; the latter property is particularly evident when the quantities of valine and alanine residues are compared. The synthesis of each enzyme is also under different regulatory constraints, being controlled by the substrate used for growth.", "contents": "Bacterial metabolism of resorcinylic compounds: purification and properties of orcinol hydroxylase and resorcinol hydroxylase from Pseudomonas putida ORC. The hydroxylase activities observed in extracts of Pseudomonas putida ORC after growth on orcinol and resorcinol as sole source of carbon have been purified to homogeneity. Both enzymes were shown to be flavoproteins and to contain approximately 1 mol of FAD for each polypeptide chain, S20,W values for each enzyme are 4.1 +/- 0.1 and are independent of the presence of their aromatic substrates. Molecular weight determinations under native (approximately 68000) and denaturing (approximately 70000) conditions indicated that they are monomeric. The visible absorption spectra identical but the circular dichroic spectra of the two proteins can be distinguished. Although each protein catalyzes the NAD(P)H and O2-dependent hydroxylation of both orcinol and resorcinol, the efficiency of the transformations of the substrates by the two enzymes is radically different; furthermore resorcinol hydroxylase is much more versatile in the aromatic compounds it can utilize as substrates and effectors. Other properties of the enzymes which clearly establish their own identity include their serological characteristics and amino acid composition; the latter property is particularly evident when the quantities of valine and alanine residues are compared. The synthesis of each enzyme is also under different regulatory constraints, being controlled by the substrate used for growth."}
{"id": "PMID:1291", "title": "[Possible structural-functional organization of the system of local cerebral blood flow regulation].", "content": "rCBF under normal conditions in the rabbit, cat, and monkey brain was found to have a spontaneous periodicity while rCBF responses to afferent flicker stimulation usually revealed a double-phasic fluctuative pattern. This suggests that the rCBF regulatory system consists of not less than two regulatory chains with different time constants, and a feedback. The data on cerebral vascular responses to microapplication of mCSF solutions with various pH, potassium and catecholamines concentrations, suggest that rapid regulatory chains may be conditioned by potassium and neurogenic vascular effects, while slow ones could be mediated by CO2 and related pH changes.", "contents": "[Possible structural-functional organization of the system of local cerebral blood flow regulation]. rCBF under normal conditions in the rabbit, cat, and monkey brain was found to have a spontaneous periodicity while rCBF responses to afferent flicker stimulation usually revealed a double-phasic fluctuative pattern. This suggests that the rCBF regulatory system consists of not less than two regulatory chains with different time constants, and a feedback. The data on cerebral vascular responses to microapplication of mCSF solutions with various pH, potassium and catecholamines concentrations, suggest that rapid regulatory chains may be conditioned by potassium and neurogenic vascular effects, while slow ones could be mediated by CO2 and related pH changes."}
{"id": "PMID:1292", "title": "[Regulation of local tissue PO2 in the cerebral cortex of the cat].", "content": "Local PO2 was measured in the cat cortex on adjacent sites with a platinum multiwire surface electrode both during steady state conditions and with varying arterial oxygen supply. Concomitantly, PO2 in the sinus sagittalis was recorded continuously through the vascular wall. Under normoxia and steady state conditions local tissue PO2 values varied between O Torr and almost arterial levels of 85 Torr in accordance with theoretical calculations. With increased arterial oxygen supply local tissue PO2 as measured on agjacent sites was found to react fairly differently. Linear increases in local tissue PO2 as compared with arterial PO2, as well as constant levels, or only very small increases, were recorded. The constancy of local PO2 (=\"local PO2 autoregulation\") was caused by local vasoconstriction. With reduced supply of arterial oxygen, however, tissue PO2 dropped in all studied sites down to hypoxia and anoxia. PO2 autoregulation during a decrease in arterial PO2, as described by Bicher (1973) could not be found.", "contents": "[Regulation of local tissue PO2 in the cerebral cortex of the cat]. Local PO2 was measured in the cat cortex on adjacent sites with a platinum multiwire surface electrode both during steady state conditions and with varying arterial oxygen supply. Concomitantly, PO2 in the sinus sagittalis was recorded continuously through the vascular wall. Under normoxia and steady state conditions local tissue PO2 values varied between O Torr and almost arterial levels of 85 Torr in accordance with theoretical calculations. With increased arterial oxygen supply local tissue PO2 as measured on agjacent sites was found to react fairly differently. Linear increases in local tissue PO2 as compared with arterial PO2, as well as constant levels, or only very small increases, were recorded. The constancy of local PO2 (=\"local PO2 autoregulation\") was caused by local vasoconstriction. With reduced supply of arterial oxygen, however, tissue PO2 dropped in all studied sites down to hypoxia and anoxia. PO2 autoregulation during a decrease in arterial PO2, as described by Bicher (1973) could not be found."}
{"id": "PMID:1293", "title": "[Differences in the responses of taste receptors to organic and inorganic acids with changes in the concentration of bicarbonate in the solution].", "content": "The thresholds of the pH for citric acid (pH=4.9) were found to exceed by 1.4 pH the thresholds for HC1 (3.5) at 1.2 mmol/1 bicarbonate in the solution. The reaction to citric acid was higher than to HC1 at equal pH. Decreasing of bicarbonate from 1.2 mmol/1 to 0 reduced pH threshold only for sitric acid from 4.90 to 3.15. pH threshold for HC1 remained 3.5 The chorda tympani response to stimulation with solutions containing bicarbonate (1.2 mmol/1) was higher than in absence of bicarbonate. The data obtained suggest two ranges of the acids in action.", "contents": "[Differences in the responses of taste receptors to organic and inorganic acids with changes in the concentration of bicarbonate in the solution]. The thresholds of the pH for citric acid (pH=4.9) were found to exceed by 1.4 pH the thresholds for HC1 (3.5) at 1.2 mmol/1 bicarbonate in the solution. The reaction to citric acid was higher than to HC1 at equal pH. Decreasing of bicarbonate from 1.2 mmol/1 to 0 reduced pH threshold only for sitric acid from 4.90 to 3.15. pH threshold for HC1 remained 3.5 The chorda tympani response to stimulation with solutions containing bicarbonate (1.2 mmol/1) was higher than in absence of bicarbonate. The data obtained suggest two ranges of the acids in action."}
{"id": "PMID:1295", "title": "Analysis of skin grafts across the MSA-barrier in mice pretreated with sera from specifically or syngeeically grafted donors.", "content": "Prolonged survival of weakly incompatible skin allografts in mice (across the barrier presented by the MSA) can be induced by pretreating the recipients not only with a specific anti-MSA serum (obtained on day 5 after a single MSA-incompatible skin graft) but also be means of control serum obtained in a similar way from the recipients of fully compatible (syngeneic) skin grafts. Administration of serum from non-grafted mice had no effect on graft survival. The similar biological effect of both sera had a counterpart in their similar content and spectrum of glycosaminoglycans. Also in the skin grafts themselves, the course of both qualitative and quantitative changes of GAG in the early postgrafting period was in the allogeneic and syngeneic situation similar. The possible role of these substances in the serum and at the site of grafting and their effect on the outcome of the allograft response are discussed.", "contents": "Analysis of skin grafts across the MSA-barrier in mice pretreated with sera from specifically or syngeeically grafted donors. Prolonged survival of weakly incompatible skin allografts in mice (across the barrier presented by the MSA) can be induced by pretreating the recipients not only with a specific anti-MSA serum (obtained on day 5 after a single MSA-incompatible skin graft) but also be means of control serum obtained in a similar way from the recipients of fully compatible (syngeneic) skin grafts. Administration of serum from non-grafted mice had no effect on graft survival. The similar biological effect of both sera had a counterpart in their similar content and spectrum of glycosaminoglycans. Also in the skin grafts themselves, the course of both qualitative and quantitative changes of GAG in the early postgrafting period was in the allogeneic and syngeneic situation similar. The possible role of these substances in the serum and at the site of grafting and their effect on the outcome of the allograft response are discussed."}
{"id": "PMID:1298", "title": "Effect of normal and ulcer-type diet on the acidity of gastric contents in patients with duodenal ulcer.", "content": "Patients with uncomplicated duodenal ulcer were given two types of diet -a normal and a ulcer-type diet. The data obtained did not show any statistically significant difference between the action of the two diets. No evidence was then found to be in support of the still widely used restricted diet in the treatment of peptic ulcer.", "contents": "Effect of normal and ulcer-type diet on the acidity of gastric contents in patients with duodenal ulcer. Patients with uncomplicated duodenal ulcer were given two types of diet -a normal and a ulcer-type diet. The data obtained did not show any statistically significant difference between the action of the two diets. No evidence was then found to be in support of the still widely used restricted diet in the treatment of peptic ulcer."}
{"id": "PMID:1296", "title": "Impaired Sertoli cell function in experimental cryptorchidism in the rat.", "content": "The production of testicular androgen-binding protein (ABP), as a measure of Sertoli cell function, was studied after unilateral or bilateral experimental cryptorchidism in adult rats. Two or 4 weeks after the testis had been translocated to the abdomen, no major changes were found in the concentration of ABP per mg protein, although there was a marked and progressive decrease in ABP content per testis. However, the rate of ABP production was greatly decreased, as measured by the accumulation of ABP during 16-h ligation of the efferent ducts or by the production of ABP by testis mince in an in vitro system. This indicates that the Sertoli cell function is severly impaired by the intra-abdominal position.", "contents": "Impaired Sertoli cell function in experimental cryptorchidism in the rat. The production of testicular androgen-binding protein (ABP), as a measure of Sertoli cell function, was studied after unilateral or bilateral experimental cryptorchidism in adult rats. Two or 4 weeks after the testis had been translocated to the abdomen, no major changes were found in the concentration of ABP per mg protein, although there was a marked and progressive decrease in ABP content per testis. However, the rate of ABP production was greatly decreased, as measured by the accumulation of ABP during 16-h ligation of the efferent ducts or by the production of ABP by testis mince in an in vitro system. This indicates that the Sertoli cell function is severly impaired by the intra-abdominal position."}
{"id": "PMID:1319", "title": "The oxygen transport system of red blood cells during diabetic ketoacidosis and recovery.", "content": "Daily evaluations of 8 newly detected ketoacidotic diabetics showed the Bohr-effect of haemoglobin to be decreased by 50% while erythrocyte 2,3-DPG was decreased below 10 mumoles/g Hb. 2,3-DPG correlated strongly with pH during acidosis and with plasma inorganic phosphate (Pi) subsequently to the first insulin administration. Oxygen affinity of haemoglobin, measured as P50 act pH, was unchanged in ketoacidosis compared to the time, however, P50 act pH fell striking (p less than 0.001) and remained decreased up to 7 days depending upon the resynthesis of 2,3-DPG in relation to Pi. The Hill-coefeficient in reflecting the slope of the oxygen dissociation curve was diminished in ketoacidosis (p less than 0.005), and decreased further after pH-normalization (p less than 0.005). There was a close association of n with 2,3-DPG (p less than 0.001) and additionally with Pi at 2,3-DPG-levels below 10 mumoles/g Hb. Based on these findings a decreased erythrocyte oxygen release of one fifth during acidosis and more than one third after pH-correction can be hypothesised. In view of the intimate relation of Pi to the oxygen transport system it is suggesed that treatment of ketoacidosis should include Pi-sugstitution.", "contents": "The oxygen transport system of red blood cells during diabetic ketoacidosis and recovery. Daily evaluations of 8 newly detected ketoacidotic diabetics showed the Bohr-effect of haemoglobin to be decreased by 50% while erythrocyte 2,3-DPG was decreased below 10 mumoles/g Hb. 2,3-DPG correlated strongly with pH during acidosis and with plasma inorganic phosphate (Pi) subsequently to the first insulin administration. Oxygen affinity of haemoglobin, measured as P50 act pH, was unchanged in ketoacidosis compared to the time, however, P50 act pH fell striking (p less than 0.001) and remained decreased up to 7 days depending upon the resynthesis of 2,3-DPG in relation to Pi. The Hill-coefeficient in reflecting the slope of the oxygen dissociation curve was diminished in ketoacidosis (p less than 0.005), and decreased further after pH-normalization (p less than 0.005). There was a close association of n with 2,3-DPG (p less than 0.001) and additionally with Pi at 2,3-DPG-levels below 10 mumoles/g Hb. Based on these findings a decreased erythrocyte oxygen release of one fifth during acidosis and more than one third after pH-correction can be hypothesised. In view of the intimate relation of Pi to the oxygen transport system it is suggesed that treatment of ketoacidosis should include Pi-sugstitution."}
{"id": "PMID:1320", "title": "Fluorescence of oxidized flavoproteins from perifused isolated pancreatic islets.", "content": "In perifused pancreatic islets, the fluorescence of oxidized flavoproteins (FAD) was recorded continuously. Elevation of glucose concentration in the medium form 0 or 5 mM to 20 mM led to decrease in FAD-fluorescence beginning 10 sec after change of medium. L-leucine (10 mM), (+/-)-B-BCH (20 mM) and alpha-ketoisocaproic acid (10 mM) caused typical kinetics of FAD-fluorescence decrease. The results are interpreted to indicate rapid changes of the functional state of B-cell mitochondria induced by the above-mentioned stimulators of insulin release.", "contents": "Fluorescence of oxidized flavoproteins from perifused isolated pancreatic islets. In perifused pancreatic islets, the fluorescence of oxidized flavoproteins (FAD) was recorded continuously. Elevation of glucose concentration in the medium form 0 or 5 mM to 20 mM led to decrease in FAD-fluorescence beginning 10 sec after change of medium. L-leucine (10 mM), (+/-)-B-BCH (20 mM) and alpha-ketoisocaproic acid (10 mM) caused typical kinetics of FAD-fluorescence decrease. The results are interpreted to indicate rapid changes of the functional state of B-cell mitochondria induced by the above-mentioned stimulators of insulin release."}
{"id": "PMID:1322", "title": "Comparison of amino acids bathing the oxyntic gland area in the stimulation of gastric secretion.", "content": "This study was undertaken to compare the ability of L- and D-isomers of amino acids bathing the oxyntic gland area to stimulate acid secretion in conscious dogs with Heidenhain pouch (HP), gastric fistula (GF) and pancreatic fistula (PF). Acid outputs from HP were determined by an intragastric titration method when amino acid solutions were perfused into HP at various concentrations, pH values, and distention pressures. Only L-isomers of all natural amino acids were found to stimulate acid secretion, whereas D-isomers of amino acids tested were completely inert in this respect. The comparison of the secretagogue activity of amino acids shows that L-histidine among essential amino acids and glycine among nonessential amino acids exhibited the strongest stimulation of acid outputs, reaching, respectively, 52 and 40% of the maximal response to histamine. Decreasing the pH of L-histidine solution perfused into HP in sequential order from 5.0 to 1.0 resulted in a stepwise reduction of acid output, falling at pH 1.0 to about 40% of the peak response achieved at pH 5.0. Local irrigation of HP by 2% xylocaine and intravenous infusion of atropine (100 mug per kg per hr) or metiamide (2.9 mg per kg per hr) reduced but did not abolish HP response to chemical stimulation and the pH dependency of this response. We conclude that only L- and not D-isomers of amino acids bathing the oxyntic gland area stimulate acid secretion by a local, gastrin-independent mechanism sensitive to distention pressure and pH.", "contents": "Comparison of amino acids bathing the oxyntic gland area in the stimulation of gastric secretion. This study was undertaken to compare the ability of L- and D-isomers of amino acids bathing the oxyntic gland area to stimulate acid secretion in conscious dogs with Heidenhain pouch (HP), gastric fistula (GF) and pancreatic fistula (PF). Acid outputs from HP were determined by an intragastric titration method when amino acid solutions were perfused into HP at various concentrations, pH values, and distention pressures. Only L-isomers of all natural amino acids were found to stimulate acid secretion, whereas D-isomers of amino acids tested were completely inert in this respect. The comparison of the secretagogue activity of amino acids shows that L-histidine among essential amino acids and glycine among nonessential amino acids exhibited the strongest stimulation of acid outputs, reaching, respectively, 52 and 40% of the maximal response to histamine. Decreasing the pH of L-histidine solution perfused into HP in sequential order from 5.0 to 1.0 resulted in a stepwise reduction of acid output, falling at pH 1.0 to about 40% of the peak response achieved at pH 5.0. Local irrigation of HP by 2% xylocaine and intravenous infusion of atropine (100 mug per kg per hr) or metiamide (2.9 mg per kg per hr) reduced but did not abolish HP response to chemical stimulation and the pH dependency of this response. We conclude that only L- and not D-isomers of amino acids bathing the oxyntic gland area stimulate acid secretion by a local, gastrin-independent mechanism sensitive to distention pressure and pH."}
{"id": "PMID:1323", "title": "Evidence of tandem duplication of genes in a merodiploid region of Pneumococcal mutants resistant to sulfonamide.", "content": "A Pneumococcal mutant, sulr-c, resistant to sulfonamides, and three transformants bearing associated d or d+ resistance markers have earlier been reported to be unstable and show distinct patterns and frequencies of segregating stable progeny lacking the c marker. Each of the four strains showed a characteristic dosage of the genes involved in the merodiploidy. Complementary strands of DNA's from these stable and unstable strains were resolved and homoduplex and heteroduplex hybrids made from the separated DNA strands were used as donors in genetic transformations. Activities of a normal marker (streptomycin resistance) and those involved in the heterozygosity (c, d and d+) were quantitatively measured. From those heteroduplexes made up of opposite strands derived from a heterozygote and a stable strain, the normal marker is transferred efficiently, but the heterozygous markers are not. On the other hand, if both strands of a heteroduplex are derived from different heterozygotic strains, all markers can be transferred with usual efficiency to a stable recipient strain. The lowered efficiency in the former type of heteroduplex is attributed to an inhomology resulting from a tandem duplication in the merodiploid strains, and a postulated DNA repair process stimulated by it while in the form of the donor duplex. The inhomology probably includes (a) a microheterogeneity between the c site and the wild type locus, and (b) a more extensive incompatibility attributable to an extra segment of genome in a tandem duplication covering the c and d sites. The first of these inhomologies produces a lowered efficiency of transfer from all configurations of the particular d allele associated with the mutant c marker, and therefore accounts for the characteristic transfer patterns even from the native merodiploid DNA's.", "contents": "Evidence of tandem duplication of genes in a merodiploid region of Pneumococcal mutants resistant to sulfonamide. A Pneumococcal mutant, sulr-c, resistant to sulfonamides, and three transformants bearing associated d or d+ resistance markers have earlier been reported to be unstable and show distinct patterns and frequencies of segregating stable progeny lacking the c marker. Each of the four strains showed a characteristic dosage of the genes involved in the merodiploidy. Complementary strands of DNA's from these stable and unstable strains were resolved and homoduplex and heteroduplex hybrids made from the separated DNA strands were used as donors in genetic transformations. Activities of a normal marker (streptomycin resistance) and those involved in the heterozygosity (c, d and d+) were quantitatively measured. From those heteroduplexes made up of opposite strands derived from a heterozygote and a stable strain, the normal marker is transferred efficiently, but the heterozygous markers are not. On the other hand, if both strands of a heteroduplex are derived from different heterozygotic strains, all markers can be transferred with usual efficiency to a stable recipient strain. The lowered efficiency in the former type of heteroduplex is attributed to an inhomology resulting from a tandem duplication in the merodiploid strains, and a postulated DNA repair process stimulated by it while in the form of the donor duplex. The inhomology probably includes (a) a microheterogeneity between the c site and the wild type locus, and (b) a more extensive incompatibility attributable to an extra segment of genome in a tandem duplication covering the c and d sites. The first of these inhomologies produces a lowered efficiency of transfer from all configurations of the particular d allele associated with the mutant c marker, and therefore accounts for the characteristic transfer patterns even from the native merodiploid DNA's."}
{"id": "PMID:1324", "title": "A study of Pneumococcal merodiploids at the molecular level.", "content": "The DNA of a sulfonamide-resistant Pneumococcal strain (heterozygous for sulr-c) and that of three highly resistant and persistently heterozygous cd transformants, derived by introducing sulr-c marker into a stable sulfonamide resistant strain (sulr-d), were studied to analyze the genetic basis of their merodiploidy. The physical properties of the native and denatured DNA from the heterozygotes and the nonheterozygous strains were not distinguishable. The denaturability and the renaturability of biological activity for the heterozygous markers were essentially identical to those of the normal markers. The heterozygosity extends to the closely linked locus giving rise to four different configurations of cd and cd+ transformants, characterized by their frequencies of segregation and donor-marker activities. The marker-activity ratios and the frequency of co-transfer of heterozygous markers were found to remain the same in each when the donor DNA was native, denatured or reannealed without fractionation or reannealed after remixing of resolved strands. Possible models were weighed against these observations and these considerations led to the suggestion that tandem duplication of a gene region may be responsible for the heterozygosity and instability of this region. A more detailed examination of this model will be presented in an accompanying paper.", "contents": "A study of Pneumococcal merodiploids at the molecular level. The DNA of a sulfonamide-resistant Pneumococcal strain (heterozygous for sulr-c) and that of three highly resistant and persistently heterozygous cd transformants, derived by introducing sulr-c marker into a stable sulfonamide resistant strain (sulr-d), were studied to analyze the genetic basis of their merodiploidy. The physical properties of the native and denatured DNA from the heterozygotes and the nonheterozygous strains were not distinguishable. The denaturability and the renaturability of biological activity for the heterozygous markers were essentially identical to those of the normal markers. The heterozygosity extends to the closely linked locus giving rise to four different configurations of cd and cd+ transformants, characterized by their frequencies of segregation and donor-marker activities. The marker-activity ratios and the frequency of co-transfer of heterozygous markers were found to remain the same in each when the donor DNA was native, denatured or reannealed without fractionation or reannealed after remixing of resolved strands. Possible models were weighed against these observations and these considerations led to the suggestion that tandem duplication of a gene region may be responsible for the heterozygosity and instability of this region. A more detailed examination of this model will be presented in an accompanying paper."}
{"id": "PMID:1325", "title": "Genetic hybridization at the unlinked thy and str loci of Streptococcus.", "content": "The sanguis and pneumoniae species of Streptococcus were used as recipients in transformations from str+ to str-r and from thy- to thy+. The str-r mutations in the two species had been previously shown to be allelic. Homology of the thy- mutations in the two species was demonstrated in the similar phenotypic properties they conferred (death in the absence of thymidine, lack of thymidylate synthetase). The str and thy loci are unlinked in each species.--- When the two species are transformed by both homospecific and heterospecific DNA, the efficiency is always lower in the heterospecific cross. The efficiency of heterospecific transformation is considerably lower at the thy than at the str locus. DNA was extracted from recipients that had integrated markers of heterospecific origin. When such hybrid DNA is tested on the original recipient species, the heterospecific markers are usually as efficient as homospecific markers. When tested on the original donor species, however, the hybrid DNA is usually more efficient than heterospecific DNA. This is true for both thy and str transformation. -- -- Forty independent thy+ hybrids were obtained in the cross of sanguis thy- recipients with pneumoniae thy+ DNA. These hybrids fall into a number of classes based upon the relative efficiency with which their extracted DNA's are able to transfer the thy+ marker into pneumoniae thy- cells. The most efficient of these DNA's exhibits about 20% of the efficiency of homospecific pneumoniae thy+ DNA and three orders of magnitude greater efficiency than heterospecific sanguis thy+ DNA. Thus, very little of the inefficiency of heterospecific transformation of the thy locus is ascribable to a classic restriction mechanism. Rather, the wild-type thy+ loci in the two species appear to differ at multiple sites, and independent heterospecific transfers result in differential extents of integration of these sites. On this basis, the thy+ loci of the two species differ at a greater number of sites than do the respective str+ loci.", "contents": "Genetic hybridization at the unlinked thy and str loci of Streptococcus. The sanguis and pneumoniae species of Streptococcus were used as recipients in transformations from str+ to str-r and from thy- to thy+. The str-r mutations in the two species had been previously shown to be allelic. Homology of the thy- mutations in the two species was demonstrated in the similar phenotypic properties they conferred (death in the absence of thymidine, lack of thymidylate synthetase). The str and thy loci are unlinked in each species.--- When the two species are transformed by both homospecific and heterospecific DNA, the efficiency is always lower in the heterospecific cross. The efficiency of heterospecific transformation is considerably lower at the thy than at the str locus. DNA was extracted from recipients that had integrated markers of heterospecific origin. When such hybrid DNA is tested on the original recipient species, the heterospecific markers are usually as efficient as homospecific markers. When tested on the original donor species, however, the hybrid DNA is usually more efficient than heterospecific DNA. This is true for both thy and str transformation. -- -- Forty independent thy+ hybrids were obtained in the cross of sanguis thy- recipients with pneumoniae thy+ DNA. These hybrids fall into a number of classes based upon the relative efficiency with which their extracted DNA's are able to transfer the thy+ marker into pneumoniae thy- cells. The most efficient of these DNA's exhibits about 20% of the efficiency of homospecific pneumoniae thy+ DNA and three orders of magnitude greater efficiency than heterospecific sanguis thy+ DNA. Thus, very little of the inefficiency of heterospecific transformation of the thy locus is ascribable to a classic restriction mechanism. Rather, the wild-type thy+ loci in the two species appear to differ at multiple sites, and independent heterospecific transfers result in differential extents of integration of these sites. On this basis, the thy+ loci of the two species differ at a greater number of sites than do the respective str+ loci."}
{"id": "PMID:1332", "title": "Fibrin plate method with reagents purified by affinity chromatography and its use for determination of fibrinolytic and other proteolytic activity in saliva, bile and plasma.", "content": "A modification of the fibrin plate method is presented. Plasminogen-free human fibrinogen and plasminogen purified by affinity chromatography have been used. Fibrin plates without and with a constant amount of plasminogen and with agarose as stabilizing medium were used for the estimation of plasmin and plasminogen activator activity. Activator activity could be demonstrated in sterile bile and saliva. When plasmin activity was present, estimations of plasminogen activator were approximate. The method is sensitive, small volumes of reagents and samples are needed. The error of the method is comparatively low and the reproducibility is good.", "contents": "Fibrin plate method with reagents purified by affinity chromatography and its use for determination of fibrinolytic and other proteolytic activity in saliva, bile and plasma. A modification of the fibrin plate method is presented. Plasminogen-free human fibrinogen and plasminogen purified by affinity chromatography have been used. Fibrin plates without and with a constant amount of plasminogen and with agarose as stabilizing medium were used for the estimation of plasmin and plasminogen activator activity. Activator activity could be demonstrated in sterile bile and saliva. When plasmin activity was present, estimations of plasminogen activator were approximate. The method is sensitive, small volumes of reagents and samples are needed. The error of the method is comparatively low and the reproducibility is good."}
{"id": "PMID:1333", "title": "[Thefts without motive of gain as a psychopathologic syndrome (author's transl)].", "content": "Thefts without motive of pain have been known since the early 19th century. But the problem has not been solved. While they were formerly considered a mental disease, today they are not seen as something special. But they still happen. Only a small percentage of common shop-lifting can be called a psycholopathologic syndrome. Many explanations and analyses have been published which are discussed in detail. In a group described here comprehensively difficult marital situations full of conflict, marital sexual frustration, depression, physical and mental exhaustion and aggressive and suicidal tendencies are found. Theft appears to be closely connected with these. But the pattern of motivation and causation is by no means stereo-typed. In order to clear up such actions one will have to consider as exactly as possible the biographic connection and what happens during the act - quite apart from somatic conditions. Present assessment in reports is totally unsatisfactory. To clear up the controversial questions is urgently necessary.", "contents": "[Thefts without motive of gain as a psychopathologic syndrome (author's transl)]. Thefts without motive of pain have been known since the early 19th century. But the problem has not been solved. While they were formerly considered a mental disease, today they are not seen as something special. But they still happen. Only a small percentage of common shop-lifting can be called a psycholopathologic syndrome. Many explanations and analyses have been published which are discussed in detail. In a group described here comprehensively difficult marital situations full of conflict, marital sexual frustration, depression, physical and mental exhaustion and aggressive and suicidal tendencies are found. Theft appears to be closely connected with these. But the pattern of motivation and causation is by no means stereo-typed. In order to clear up such actions one will have to consider as exactly as possible the biographic connection and what happens during the act - quite apart from somatic conditions. Present assessment in reports is totally unsatisfactory. To clear up the controversial questions is urgently necessary."}
{"id": "PMID:1334", "title": "The structures of the phytochrome chromophore in both photoreversible forms.", "content": "Spectral measurements of phytochrome are performed after unfolding of the peptide chain. By comparison with bile pigments of known structure, structure 1a, containing a hydrogenated ring A, is deduced for the PR chromophore. Its spectral properties indicate that the chromophore of the physiologically active PFR form has lost the double bond of the bridge joining rings A and B.", "contents": "The structures of the phytochrome chromophore in both photoreversible forms. Spectral measurements of phytochrome are performed after unfolding of the peptide chain. By comparison with bile pigments of known structure, structure 1a, containing a hydrogenated ring A, is deduced for the PR chromophore. Its spectral properties indicate that the chromophore of the physiologically active PFR form has lost the double bond of the bridge joining rings A and B."}
{"id": "PMID:1335", "title": "A micro-method for quantitative determination of acylneuraminic acids from erythrocyte membranes.", "content": "A micro-method is presented which enables the fast and exact determination of acid-hydrolyzed acylneuraminic acids in erythrocyte membranes. Erythrocytes from 1 ml of human and rabbit blood containing ACD buffer are, washed and hemolyzed on Millipore filters of pore size 1.2 mu. Acylneuraminic acids are released from the erythrocyte membranes still on the filters under the optimal conditions of 0.1 N HCl at 80 degrees C for 50 min. A prerequisite for the determination of the true amount of acylneuraminic acids using the periodic acid/thiobarbituric acid assay is the small-scale extraction of lipids from the hydrolysate and anion-exchange chromatography of acylneuraminic acids. The values thus obtained must be corrected, as 20% of acylneuraminic acids are destroyed during acid hydrolysis. In samples of human blood from 10 healthy individuals, on an average 223 nmol acylneuraminic acids per ml of packed erythrocytes were found, and in the same amount of rabbit erythrocytes, 1e method for a screening of the acylneuraminic acid content of erythrocyte membranes in hemolytic diseases or of other cell membranes is discussed.", "contents": "A micro-method for quantitative determination of acylneuraminic acids from erythrocyte membranes. A micro-method is presented which enables the fast and exact determination of acid-hydrolyzed acylneuraminic acids in erythrocyte membranes. Erythrocytes from 1 ml of human and rabbit blood containing ACD buffer are, washed and hemolyzed on Millipore filters of pore size 1.2 mu. Acylneuraminic acids are released from the erythrocyte membranes still on the filters under the optimal conditions of 0.1 N HCl at 80 degrees C for 50 min. A prerequisite for the determination of the true amount of acylneuraminic acids using the periodic acid/thiobarbituric acid assay is the small-scale extraction of lipids from the hydrolysate and anion-exchange chromatography of acylneuraminic acids. The values thus obtained must be corrected, as 20% of acylneuraminic acids are destroyed during acid hydrolysis. In samples of human blood from 10 healthy individuals, on an average 223 nmol acylneuraminic acids per ml of packed erythrocytes were found, and in the same amount of rabbit erythrocytes, 1e method for a screening of the acylneuraminic acid content of erythrocyte membranes in hemolytic diseases or of other cell membranes is discussed."}
{"id": "PMID:1336", "title": "Human liver acid phosphatases.", "content": "Human liver contains three chromatographically distinct forms of non-specific acid phosphatase (EC 3.1.3.2). Acid phosphatases I, II and III have molecular weights of greater than 200 000, of 107 000, and of 13 400, respectively. Following partial purification, isoenzyme II was obtained as a single activity band, as assessed by activity staining with p-nitrophenyl phosphate and alpha-naphthyl phosphate on polyacrylamide gels run at several pH values. With 50mM p-nitrophenyl phosphate as a substrate, enzymes II and III exhibit plateaus of activity over the pH range 3 - 5 and 3.5 - 6, respectively. Acid phosphatase II is not significantly inhibited by 0.5% formaldehyde. The activity of human liver acid phosphatase II and of human prostatic acid phosphatase towards several substrates is compared. The liver enzyme, is marked contrast to the prostatic enzyme, does not hydrolyze O-phosphoryl choline.", "contents": "Human liver acid phosphatases. Human liver contains three chromatographically distinct forms of non-specific acid phosphatase (EC 3.1.3.2). Acid phosphatases I, II and III have molecular weights of greater than 200 000, of 107 000, and of 13 400, respectively. Following partial purification, isoenzyme II was obtained as a single activity band, as assessed by activity staining with p-nitrophenyl phosphate and alpha-naphthyl phosphate on polyacrylamide gels run at several pH values. With 50mM p-nitrophenyl phosphate as a substrate, enzymes II and III exhibit plateaus of activity over the pH range 3 - 5 and 3.5 - 6, respectively. Acid phosphatase II is not significantly inhibited by 0.5% formaldehyde. The activity of human liver acid phosphatase II and of human prostatic acid phosphatase towards several substrates is compared. The liver enzyme, is marked contrast to the prostatic enzyme, does not hydrolyze O-phosphoryl choline."}
{"id": "PMID:1337", "title": "Isolation and characterization of pepsin-treated type III collagen from calf skin.", "content": "Calf skin collagen was solubilized by incubating acid-extracted calf skin with pepsin at pH 2.0 and 25 degrees C, conditions that did not cause degradation of the triple helical region of collagen. Type III collagen was separated from type I collagen by differential salt precipitation at pH 7.5. The isolated type III collagen contained mainly gamma and higher molecular weight components cross-linked by reducible and/or non-reducible bonds. The isolated alpha1 (III) chains had an amino acid composition characteristic of type III collagen. Denatured but unreduced type III collagen, chromatographed on carboxymethyl-cellulose, eluted in the alpha 2 region, while after reduction and alkylation the alpha1 (III) chains eluted between the positions of alpha1 (I) and alpha2. The mid-point melting temperature temperature (tm) of type III collagen (35.1 degrees C) in a citrate buffer at pH 3.7 was somewhat lower than that of type I collagen (35.9 degrees C). Renaturation experiments at 25 degrees C showed that denatured type III collagen molecules with intact intramolecular disulfide bridges (gamma components) reform the triple helical structure of collagen much faster than reduced and carboxymethylated alpha1 (III) chains.", "contents": "Isolation and characterization of pepsin-treated type III collagen from calf skin. Calf skin collagen was solubilized by incubating acid-extracted calf skin with pepsin at pH 2.0 and 25 degrees C, conditions that did not cause degradation of the triple helical region of collagen. Type III collagen was separated from type I collagen by differential salt precipitation at pH 7.5. The isolated type III collagen contained mainly gamma and higher molecular weight components cross-linked by reducible and/or non-reducible bonds. The isolated alpha1 (III) chains had an amino acid composition characteristic of type III collagen. Denatured but unreduced type III collagen, chromatographed on carboxymethyl-cellulose, eluted in the alpha 2 region, while after reduction and alkylation the alpha1 (III) chains eluted between the positions of alpha1 (I) and alpha2. The mid-point melting temperature temperature (tm) of type III collagen (35.1 degrees C) in a citrate buffer at pH 3.7 was somewhat lower than that of type I collagen (35.9 degrees C). Renaturation experiments at 25 degrees C showed that denatured type III collagen molecules with intact intramolecular disulfide bridges (gamma components) reform the triple helical structure of collagen much faster than reduced and carboxymethylated alpha1 (III) chains."}
{"id": "PMID:1338", "title": "High-dosage and versatile drug therapy with treatment-resistant psychotic patients.", "content": "The author believes that many of the chronic patients in psychiatric institutions and mental health facilities could be helped if physicians were more willing to try different combinations and higher dosages of psychotropic drugs than are commonly used. He presents case studies of two chronic patients who were helped by innovative use of drugs and discusses factors to be considered in implementing high-dosage and versatile drug therapy.", "contents": "High-dosage and versatile drug therapy with treatment-resistant psychotic patients. The author believes that many of the chronic patients in psychiatric institutions and mental health facilities could be helped if physicians were more willing to try different combinations and higher dosages of psychotropic drugs than are commonly used. He presents case studies of two chronic patients who were helped by innovative use of drugs and discusses factors to be considered in implementing high-dosage and versatile drug therapy."}
{"id": "PMID:1339", "title": "A new variant of glucosephosphate isomerase deficiency.", "content": "A new variant of glucose-6-phosphate isomerase deficiency is described. The enzyme kinetics and properties were studied. Genetic and electrophoretic data pointed to a double heterozygous state in the patient. These data are compared to the other variants described in the literature until now.", "contents": "A new variant of glucosephosphate isomerase deficiency. A new variant of glucose-6-phosphate isomerase deficiency is described. The enzyme kinetics and properties were studied. Genetic and electrophoretic data pointed to a double heterozygous state in the patient. These data are compared to the other variants described in the literature until now."}
{"id": "PMID:1344", "title": "[Infusion treatment in shock].", "content": "Nowadays, above all dextran, gelatin and starch solutions are available for the infusion theraphy of the various forms of shock. The application of these volume substitutes must be strictly controlled to avoid in particular cardial and pulmonal commplications. Blood transfusion combined with a volume substitute should only be applied in cases of heavy loss of blood. The treatment of metabolic acidose which usually occurs simultaneously is carried out with an alkaline solution.", "contents": "[Infusion treatment in shock]. Nowadays, above all dextran, gelatin and starch solutions are available for the infusion theraphy of the various forms of shock. The application of these volume substitutes must be strictly controlled to avoid in particular cardial and pulmonal commplications. Blood transfusion combined with a volume substitute should only be applied in cases of heavy loss of blood. The treatment of metabolic acidose which usually occurs simultaneously is carried out with an alkaline solution."}
{"id": "PMID:1345", "title": "Suppressor T cells and host resistance to tye 111 pneumococcus after treatment with antilymphocyte serum.", "content": "The antibody response to type III pneumococcal polysaccharide (SS-II) was significantly increased in mice treated with antilymphocyte serum (ALS). BALG/c mice given 0.25 ml of ALS on days -1, 0, and 1 relative to the days of immunization with 0.5 mug of SSS-II had a 20-fold increment (11,383 increased to 199,917) in the number of splenic plaque-forming cells enumerated on day 5 compared with untreated, immunized controls. This effect has been attributed to the elimination of subpopulation of thymus-derived lymphocytes (T cells) that has suppressor function. The present series of experiments relate the augmented antibody response to SSS-II in mice treated with ALS to increased host resistance after infection with Streptococcus pneumoniae, type III (Pn-II). The 50%  lethal dose of Pn-III in niminnunized mice was 102 and the 100% lethal dose was 103 organisms. Mice immunized with 0.5 mug of SSS-III and challenged 5 days later with Pn-III were completely protected against a dose of up to 108 organisms. Mice treated with 0.25 ml of ALS on days -1, 0, and 1, immunized with SSS-III on day 0, and challenged with 2.5 X 10(9) Pn-III on day 5 had a mean survival time of greater than 100 h compared with 16 h for immunized non-serum-treated controls. Animals given a single injection of ALS before immunization showed no increase in resistance, whereas mice treated after immunization had significant prolongation of survival times. Untreated, immunized mice challenged with 5 X 10(9), 1 X 5 X 10(8) Pn-II survived 14 to 19 h, whereas ALS-treated animals had mean survival times of 48, 174, and 222 h, respectively. These findings suggest that immunoregulatory T cells may have a biologically significant effect in a narrow zone in which the normal host immune response is insufficient but still potentially capable of providing some additional degree of protection if suppressor cells are elimated.", "contents": "Suppressor T cells and host resistance to tye 111 pneumococcus after treatment with antilymphocyte serum. The antibody response to type III pneumococcal polysaccharide (SS-II) was significantly increased in mice treated with antilymphocyte serum (ALS). BALG/c mice given 0.25 ml of ALS on days -1, 0, and 1 relative to the days of immunization with 0.5 mug of SSS-II had a 20-fold increment (11,383 increased to 199,917) in the number of splenic plaque-forming cells enumerated on day 5 compared with untreated, immunized controls. This effect has been attributed to the elimination of subpopulation of thymus-derived lymphocytes (T cells) that has suppressor function. The present series of experiments relate the augmented antibody response to SSS-II in mice treated with ALS to increased host resistance after infection with Streptococcus pneumoniae, type III (Pn-II). The 50%  lethal dose of Pn-III in niminnunized mice was 102 and the 100% lethal dose was 103 organisms. Mice immunized with 0.5 mug of SSS-III and challenged 5 days later with Pn-III were completely protected against a dose of up to 108 organisms. Mice treated with 0.25 ml of ALS on days -1, 0, and 1, immunized with SSS-III on day 0, and challenged with 2.5 X 10(9) Pn-III on day 5 had a mean survival time of greater than 100 h compared with 16 h for immunized non-serum-treated controls. Animals given a single injection of ALS before immunization showed no increase in resistance, whereas mice treated after immunization had significant prolongation of survival times. Untreated, immunized mice challenged with 5 X 10(9), 1 X 5 X 10(8) Pn-II survived 14 to 19 h, whereas ALS-treated animals had mean survival times of 48, 174, and 222 h, respectively. These findings suggest that immunoregulatory T cells may have a biologically significant effect in a narrow zone in which the normal host immune response is insufficient but still potentially capable of providing some additional degree of protection if suppressor cells are elimated."}
{"id": "PMID:1346", "title": "[Past and present aspects of diarrheal disease in childhood. Clinical study and treatment (author's transl)].", "content": "The etiologic and pathophysiologic findings described in the first part of this paper have important consequences: The recognition of the specific etiology of diarrhea requires new laboratory methods: most of these, however, are technically easy to perform and do not require a large laboratory. A long-ranging consequence of this changed concept is a well-founded modification of therapy. The most important discovery was, that in a well balanced glucose electrolyte solution sodium and glucose enhance their absorption mutually and increase the absorption of water by solvent drag. Since in most acute diarrheas the mechanisms of absorption of glucose and electrolytes are retained this mechanism can be utilized for fast oral rehydration and reinstitution of normal intestinal homeostasis. Prompt institution of a diet consisting of the previously mentioned glucose-electrolyte solution usually prevents severe dehydration and the need for stationary treatment. The elimination of lactose and long chain fatty acids from the diet prevents continuation of the pathologic osmotic and chemical conditions in the intestine. Antibiotics are not indicated in acute diarrhea with the exception of diarrhea caused by enteroinvasive E. Coli or Shigella, in the case of Salmonella-gastroenteritis even contraindicated. Further research concentrates on the development of drugs for neutralisation of E. Coli enterotoxin and the prevention of diarrheas by development of effective vaccines.", "contents": "[Past and present aspects of diarrheal disease in childhood. Clinical study and treatment (author's transl)]. The etiologic and pathophysiologic findings described in the first part of this paper have important consequences: The recognition of the specific etiology of diarrhea requires new laboratory methods: most of these, however, are technically easy to perform and do not require a large laboratory. A long-ranging consequence of this changed concept is a well-founded modification of therapy. The most important discovery was, that in a well balanced glucose electrolyte solution sodium and glucose enhance their absorption mutually and increase the absorption of water by solvent drag. Since in most acute diarrheas the mechanisms of absorption of glucose and electrolytes are retained this mechanism can be utilized for fast oral rehydration and reinstitution of normal intestinal homeostasis. Prompt institution of a diet consisting of the previously mentioned glucose-electrolyte solution usually prevents severe dehydration and the need for stationary treatment. The elimination of lactose and long chain fatty acids from the diet prevents continuation of the pathologic osmotic and chemical conditions in the intestine. Antibiotics are not indicated in acute diarrhea with the exception of diarrhea caused by enteroinvasive E. Coli or Shigella, in the case of Salmonella-gastroenteritis even contraindicated. Further research concentrates on the development of drugs for neutralisation of E. Coli enterotoxin and the prevention of diarrheas by development of effective vaccines."}
{"id": "PMID:1349", "title": "Population growth-a menace to what?", "content": "Originally, many of the initiators of the World Population Conference, which took place in Bucharest in 1974, had hoped that the Conference would imply a final breakthrough for the view that family planning measures should be given top priority in all less-developed countries. In fact, however, the Plan of Action passed by the Conference contains very little relating to population and family planning. Instead, the document is dominated by wordy phrases about the necessity of attaining social and economic development in those countries. Will the insight that family planning programs work efficiently only if they are an integral part of programs for the social and economic development of a country lead to such programs being realized? There is every reason to doubt that the plan of Action will have any such effect. The reasons for the underdevelopment of Third World countries cannot be removed through such United Nations resolutions. In the People's Republic of China, family planning is widely accepted, especially in the towns, and now also among the rural population. Limiting the number of children is considered part of China's development effort. China is a less-developed country that is in the process of rapid social and economic development. The issue at stake in other Third World countries is how to achieve a similar development. As soon as this goal is achieved, family planning efforts are meaningful and have a chance of success. The experience of China demonstrates that even there it took time before the efforts succeeded. There are many Third World countries that could, without much difficulty, support a population considerably larger than the present one. But there are no doubt also a number of countries where the population is already so large that a continued population increase would be harmful. The need to achieve rapid development becomes increasingly urgent, not in the least to make it possible to attain a reduced population growth. The sad truth is that so little development takes place in those countries. Without social and economic development, the present rapid population increase will continue in those countries where there is already an overly dense population.", "contents": "Population growth-a menace to what? Originally, many of the initiators of the World Population Conference, which took place in Bucharest in 1974, had hoped that the Conference would imply a final breakthrough for the view that family planning measures should be given top priority in all less-developed countries. In fact, however, the Plan of Action passed by the Conference contains very little relating to population and family planning. Instead, the document is dominated by wordy phrases about the necessity of attaining social and economic development in those countries. Will the insight that family planning programs work efficiently only if they are an integral part of programs for the social and economic development of a country lead to such programs being realized? There is every reason to doubt that the plan of Action will have any such effect. The reasons for the underdevelopment of Third World countries cannot be removed through such United Nations resolutions. In the People's Republic of China, family planning is widely accepted, especially in the towns, and now also among the rural population. Limiting the number of children is considered part of China's development effort. China is a less-developed country that is in the process of rapid social and economic development. The issue at stake in other Third World countries is how to achieve a similar development. As soon as this goal is achieved, family planning efforts are meaningful and have a chance of success. The experience of China demonstrates that even there it took time before the efforts succeeded. There are many Third World countries that could, without much difficulty, support a population considerably larger than the present one. But there are no doubt also a number of countries where the population is already so large that a continued population increase would be harmful. The need to achieve rapid development becomes increasingly urgent, not in the least to make it possible to attain a reduced population growth. The sad truth is that so little development takes place in those countries. Without social and economic development, the present rapid population increase will continue in those countries where there is already an overly dense population."}
{"id": "PMID:1350", "title": "Training of the barefoot doctor in the People's Republic of China: from prevention to curative service.", "content": "Among the changes that have been brought about in health delivery in the People's Republic of China, the introduction of the barefoot doctor has been one of the most important and effective ways that the government has devised to radically alter the concept of health care. Through close identification with the community in terms of recruitment, training, and practice, the barefoot doctor is a concrete manifestation of the ideological principles of following the mass line and being self-reliant. The paper focuses on the building of rural health services, with special reference to the training of the barefoot doctor as the first-level contact person in primary care in the communes. It describes the training programs in a school of public health and the career mobility possible to the barefoot doctor in joining the ranks of medical practitioners.", "contents": "Training of the barefoot doctor in the People's Republic of China: from prevention to curative service. Among the changes that have been brought about in health delivery in the People's Republic of China, the introduction of the barefoot doctor has been one of the most important and effective ways that the government has devised to radically alter the concept of health care. Through close identification with the community in terms of recruitment, training, and practice, the barefoot doctor is a concrete manifestation of the ideological principles of following the mass line and being self-reliant. The paper focuses on the building of rural health services, with special reference to the training of the barefoot doctor as the first-level contact person in primary care in the communes. It describes the training programs in a school of public health and the career mobility possible to the barefoot doctor in joining the ranks of medical practitioners."}
{"id": "PMID:1351", "title": "Effect of the beta-receptor blocking agent Visken on the action of coumarin.", "content": "In a double-blind study, the influence of Visken on the effect of anticoagulant therapy with Marcoumar was examined. In comparison to a placebo group, neither any influence on the Quick time, nor any increased tendency to haemorrhage bleeding could be detected.", "contents": "Effect of the beta-receptor blocking agent Visken on the action of coumarin. In a double-blind study, the influence of Visken on the effect of anticoagulant therapy with Marcoumar was examined. In comparison to a placebo group, neither any influence on the Quick time, nor any increased tendency to haemorrhage bleeding could be detected."}
{"id": "PMID:1355", "title": "Investigations of the excretion of gamma-glutamyl-transpeptidase into the urine.", "content": "The excretion of the enzyme gamma-glutamyl-transpeptidase and its isoenzymes into the urine was investigated in patients with renal diseases and compared with the excretion of the enzymes leucine-aminopeptidase and lactate-dehydrogenase. In animal experiments an increased excretion of these enzymes was found after autotransplantation. Increased excretion of gamma-glutamyl-transpeptidase was also found in patients with glomerulonephritis and in the polyuric phase of acute tubular necrosis, but not in cases of pyelonephritis and in the oliguric phase of acute tubular necrosis. The alterations of the isoenzyme pattern during diseases with increased enzyme excretion are in accordance with the hypothesis that the enzymes are liberated from the kidney tissue into the urine, and only a minority stems from the blood. Investigation of the excretion of gamma-glutamyl-transpeptidase and its isoenzymes into the urine seems to be of both scientific and clinical interest.", "contents": "Investigations of the excretion of gamma-glutamyl-transpeptidase into the urine. The excretion of the enzyme gamma-glutamyl-transpeptidase and its isoenzymes into the urine was investigated in patients with renal diseases and compared with the excretion of the enzymes leucine-aminopeptidase and lactate-dehydrogenase. In animal experiments an increased excretion of these enzymes was found after autotransplantation. Increased excretion of gamma-glutamyl-transpeptidase was also found in patients with glomerulonephritis and in the polyuric phase of acute tubular necrosis, but not in cases of pyelonephritis and in the oliguric phase of acute tubular necrosis. The alterations of the isoenzyme pattern during diseases with increased enzyme excretion are in accordance with the hypothesis that the enzymes are liberated from the kidney tissue into the urine, and only a minority stems from the blood. Investigation of the excretion of gamma-glutamyl-transpeptidase and its isoenzymes into the urine seems to be of both scientific and clinical interest."}
{"id": "PMID:1356", "title": "Interaction of adrenergic antagonists with prostaglandin E2 and tetrahydrocannabinol in the eye.", "content": "Both alpha- and beta-adrenergic antagonists have been utilized in an atempt to discern the site of action of prostaglandin (PG) and tetrahydrocannabinol (THC) in the eye. Both alpha- and beta-adrenergic antagonists (alpha-antagonists, phentolamine and phenoxybenzamine; beta-antagonists, propranolol and sotalol) cuased a dose-dependent reduction in intraocular pressure and blood pressure and increased total outflow facility. The results are consistent with the concept that both alpha- and beta-adrenergic receptors are present in the anterior uvea and that vasomotor tone is essential to the maintenance of normal intraocular pressure. No antagonist reduced the PG-induced elevation of intraocular pressure unless the blood pressure was severely lowered. All antagonists inhibit the normal PG-induced increase in total outflow facility, indicating that these agents protect the blood-aqueous barrier from breakdown without altering the vasodilatory response to PG. All antagonists reduced the fall in intraocular pressure produced by THC by approximately 50 per cent, except for sotalol which completely abolished the intraocular pressure fall. Only the alpha-adrenergic antagonists prevented the THC-induced increase in total outflow facility. The results indicate that true outflow facility may well be regulated exclusively by alpha-receptors. The data are consistent with the effect of THC being primarily a vasodilation of the efferent blood vessels of the anterior uvea. The partial inhibition by alpha-adrenergic antagonists may also suggest a lesser role of THC on the afferent vessels.", "contents": "Interaction of adrenergic antagonists with prostaglandin E2 and tetrahydrocannabinol in the eye. Both alpha- and beta-adrenergic antagonists have been utilized in an atempt to discern the site of action of prostaglandin (PG) and tetrahydrocannabinol (THC) in the eye. Both alpha- and beta-adrenergic antagonists (alpha-antagonists, phentolamine and phenoxybenzamine; beta-antagonists, propranolol and sotalol) cuased a dose-dependent reduction in intraocular pressure and blood pressure and increased total outflow facility. The results are consistent with the concept that both alpha- and beta-adrenergic receptors are present in the anterior uvea and that vasomotor tone is essential to the maintenance of normal intraocular pressure. No antagonist reduced the PG-induced elevation of intraocular pressure unless the blood pressure was severely lowered. All antagonists inhibit the normal PG-induced increase in total outflow facility, indicating that these agents protect the blood-aqueous barrier from breakdown without altering the vasodilatory response to PG. All antagonists reduced the fall in intraocular pressure produced by THC by approximately 50 per cent, except for sotalol which completely abolished the intraocular pressure fall. Only the alpha-adrenergic antagonists prevented the THC-induced increase in total outflow facility. The results indicate that true outflow facility may well be regulated exclusively by alpha-receptors. The data are consistent with the effect of THC being primarily a vasodilation of the efferent blood vessels of the anterior uvea. The partial inhibition by alpha-adrenergic antagonists may also suggest a lesser role of THC on the afferent vessels."}
{"id": "PMID:1357", "title": "Induction of corneal graft rejection by passive cell transfer.", "content": "An experimental model is presented demonstrating that penetrating corneal grafts in the rabbit may be rejected by passive transfer into the anterior chamber of specifically sensitized lymphoid cells. Destruction of histo-incompatible corneal endothelium is always marked by the formation of focal pock-like areas of damage in this system, rather than by the typical moving line of rejecting endothelium usually seen in spontaneous graft rejection. Where the transferred lymphoid cells are compatible with the tissues of the graft recipient, the picture is one of a severely affected graft on a field of uninvolved recipient corneal endothelium. Where the lymphoid cells are compatible with the graft and not with the tissues of the recipient, one sees a clear corneal graft surviving on a field of endothelial destruction on the recipient bed. The specificity of these reactions is illustrated in terms of the histocompatibility relationships between corneal donor, graft recipient, and the donor of the sensitized lymphoid cells.", "contents": "Induction of corneal graft rejection by passive cell transfer. An experimental model is presented demonstrating that penetrating corneal grafts in the rabbit may be rejected by passive transfer into the anterior chamber of specifically sensitized lymphoid cells. Destruction of histo-incompatible corneal endothelium is always marked by the formation of focal pock-like areas of damage in this system, rather than by the typical moving line of rejecting endothelium usually seen in spontaneous graft rejection. Where the transferred lymphoid cells are compatible with the tissues of the graft recipient, the picture is one of a severely affected graft on a field of uninvolved recipient corneal endothelium. Where the lymphoid cells are compatible with the graft and not with the tissues of the recipient, one sees a clear corneal graft surviving on a field of endothelial destruction on the recipient bed. The specificity of these reactions is illustrated in terms of the histocompatibility relationships between corneal donor, graft recipient, and the donor of the sensitized lymphoid cells."}
{"id": "PMID:1358", "title": "Acute tubular necrosis.  An experimental model detailing the biochemical events accompanying renal injury and recovery.", "content": "Male Charles River mice, divided into control or experimental groups, received on Day 0 either sterile 0.3 MNaHCO3 in 0.9 per cent saline (pH7.4) intraperitoneal injection or pteroylglutamic acid (200 mug per body weight), similarly buffered to pH7.6, and were sacrificed on Days 0, 1/4, 1/2, 1,2,3,4,7, and 14. The experimental kidneys demonstrated intratubular deposits of pteroylglutamic acid with edema between  Days 1 and 4 with cortical scarring by Day 14. The experimental kidneys reached maximal increases in weight (+90 per cent) on Day 2, RNA (+61 per cent, protein (+67 per cent) on Day 3, and DNA (+25 per cent) on Day 4 before falling to below control levels on Day 14. The control kidneys demonstrated the gradual incremental increases of normal renal growth throughout this period. No change in renal size, protein, RNA, or DNA could be detected in those animals who failed to demonstrate renal tubular damage. It is postulated that the response of the kidney to folic acid administration is a reparative response and not a response directed toward accelerated renal growth.", "contents": "Acute tubular necrosis.  An experimental model detailing the biochemical events accompanying renal injury and recovery. Male Charles River mice, divided into control or experimental groups, received on Day 0 either sterile 0.3 MNaHCO3 in 0.9 per cent saline (pH7.4) intraperitoneal injection or pteroylglutamic acid (200 mug per body weight), similarly buffered to pH7.6, and were sacrificed on Days 0, 1/4, 1/2, 1,2,3,4,7, and 14. The experimental kidneys demonstrated intratubular deposits of pteroylglutamic acid with edema between  Days 1 and 4 with cortical scarring by Day 14. The experimental kidneys reached maximal increases in weight (+90 per cent) on Day 2, RNA (+61 per cent, protein (+67 per cent) on Day 3, and DNA (+25 per cent) on Day 4 before falling to below control levels on Day 14. The control kidneys demonstrated the gradual incremental increases of normal renal growth throughout this period. No change in renal size, protein, RNA, or DNA could be detected in those animals who failed to demonstrate renal tubular damage. It is postulated that the response of the kidney to folic acid administration is a reparative response and not a response directed toward accelerated renal growth."}
{"id": "PMID:1368", "title": "Properties of the 3-o-methyl-D-glucose transport system in Acholeplasma laidlawii.", "content": "Transport of 3-O-methyl-D-glucose (3-O-MG) by Acholeplasma laidlawii cells was studied. The 3-O-MG transport system appeared to be constitutive in cells grown on 3-O-MG and glucose; the transport process depended on the concentration of substrate used and exhibited typical saturation kinetics, with an apparent Km of 4.6 muM. 3-O-MG was transported as a free carbohydrate and was not metabolized further in the cell. Dependence on pH and temperature and the results of efflux and \"counterflow\" experiments demonstrated the carrier nature of the transport system. 6-Deoxyglucose and glucose competitively inhibited 3-O-MG transport, whereas maltose inhibited in non-competitively. p-Chloromercuribenzoate, p-chloromercuribenzene sulfonate, N-ethylmaleimide, and iodoacetate inhibited transport of 3-O-MG. Cells were able to accumulate 3-O-MG against a concentration gradient. Some electron transfer inhibitors (rotenone and amytal), arsenate, dicyclohexylcarbodiimide, and proton conductors such as 2,4-dinitrophenol, carbonylcyanide, m-chlorophenylhydrazone, pentachlorophenol, and tetrachlorotrifluoromethylbenzimidazole inhibited this process.", "contents": "Properties of the 3-o-methyl-D-glucose transport system in Acholeplasma laidlawii. Transport of 3-O-methyl-D-glucose (3-O-MG) by Acholeplasma laidlawii cells was studied. The 3-O-MG transport system appeared to be constitutive in cells grown on 3-O-MG and glucose; the transport process depended on the concentration of substrate used and exhibited typical saturation kinetics, with an apparent Km of 4.6 muM. 3-O-MG was transported as a free carbohydrate and was not metabolized further in the cell. Dependence on pH and temperature and the results of efflux and \"counterflow\" experiments demonstrated the carrier nature of the transport system. 6-Deoxyglucose and glucose competitively inhibited 3-O-MG transport, whereas maltose inhibited in non-competitively. p-Chloromercuribenzoate, p-chloromercuribenzene sulfonate, N-ethylmaleimide, and iodoacetate inhibited transport of 3-O-MG. Cells were able to accumulate 3-O-MG against a concentration gradient. Some electron transfer inhibitors (rotenone and amytal), arsenate, dicyclohexylcarbodiimide, and proton conductors such as 2,4-dinitrophenol, carbonylcyanide, m-chlorophenylhydrazone, pentachlorophenol, and tetrachlorotrifluoromethylbenzimidazole inhibited this process."}
{"id": "PMID:1369", "title": "Starvation survival of Salmonella enteritidis.", "content": "Washed cells of Salmonella enteritidis harvested from a defined medium during logarithmic growth were subjected to starvation in pH 7 phosphate buffer at 37 C. Viability was measured by slide cultures and plate counts. The survival of cell suspensions equivalent to 1 to 10 mg (dry wt)/ml was influenced by cryptic growth. The rate of cryptic growth, assessed by plate counts, increased with cell density and could not be alleviated by starvation with dialysis. Dialysis of the starving culture did retard the onset of cryptic growth but did not eliminate it, indicating that the major substrates for regrowth were relatively large cellular components. In phosphate buffer, 6.7 homologous heat-killed cells allowed for the doubling of one S. enteritidis cell. Cryptic growth was not observed when cells were starved on the surface of membrane filters or in suspensions equivalent to 20 mug (dry wt)/ml (105 cells/ml). Similar half-life survival times were calculated for both these populations, but the shape of their survival curves differed significantly. These differences were attributed to stress factors encountered during cell preparation and during starvation. The half-life survival time of S. enteritidis starved at 20 mug (dry wt)/ml was 140 h in phosphate buffer, 82 h in 3,6-endomethylene-1,2,3,-6-tetrahydrophthalic acid buffer, and 77 h in tris(hydroxymethyl)aminomethane buffer.", "contents": "Starvation survival of Salmonella enteritidis. Washed cells of Salmonella enteritidis harvested from a defined medium during logarithmic growth were subjected to starvation in pH 7 phosphate buffer at 37 C. Viability was measured by slide cultures and plate counts. The survival of cell suspensions equivalent to 1 to 10 mg (dry wt)/ml was influenced by cryptic growth. The rate of cryptic growth, assessed by plate counts, increased with cell density and could not be alleviated by starvation with dialysis. Dialysis of the starving culture did retard the onset of cryptic growth but did not eliminate it, indicating that the major substrates for regrowth were relatively large cellular components. In phosphate buffer, 6.7 homologous heat-killed cells allowed for the doubling of one S. enteritidis cell. Cryptic growth was not observed when cells were starved on the surface of membrane filters or in suspensions equivalent to 20 mug (dry wt)/ml (105 cells/ml). Similar half-life survival times were calculated for both these populations, but the shape of their survival curves differed significantly. These differences were attributed to stress factors encountered during cell preparation and during starvation. The half-life survival time of S. enteritidis starved at 20 mug (dry wt)/ml was 140 h in phosphate buffer, 82 h in 3,6-endomethylene-1,2,3,-6-tetrahydrophthalic acid buffer, and 77 h in tris(hydroxymethyl)aminomethane buffer."}
{"id": "PMID:1370", "title": "Mismatch correction in pneumococcal transformation: donor length and hex-dependent marker efficiency.", "content": "A hypothesis that preferential rejection of donor markers by the hex system of pneumococcus is due to lethal double-strand breaks has been examined in terms of its implications for the extent of the excision required. Experiments reported here were directed at asking whether hex-dependent marker efficiency depends on the length of the donor deoxyribonucleic acid (DNA). In the absence of intracellular competition for hex function, there was no detectable effect of DNA size on hex-dependent marker efficiency as donor DNA was sheared from greater than 1 x 107 daltons to 3.6 x 105 daltons. The latter DNA was purified by two successive velocity fractionations to ensure that the activity seen was representative of DNA of that size. Quantitative examination of the system shows that, for the lethal event hypothesis to be true, the excision step has to remove an average of 7,000 to 10,000 nucleotides. This figure is so much greater than that seen in other excision processes that alternate hypotheses should be considered. The presently known properties of the hex system can be accounted for by a model invoking the migratory features of type I restriction enzymes.", "contents": "Mismatch correction in pneumococcal transformation: donor length and hex-dependent marker efficiency. A hypothesis that preferential rejection of donor markers by the hex system of pneumococcus is due to lethal double-strand breaks has been examined in terms of its implications for the extent of the excision required. Experiments reported here were directed at asking whether hex-dependent marker efficiency depends on the length of the donor deoxyribonucleic acid (DNA). In the absence of intracellular competition for hex function, there was no detectable effect of DNA size on hex-dependent marker efficiency as donor DNA was sheared from greater than 1 x 107 daltons to 3.6 x 105 daltons. The latter DNA was purified by two successive velocity fractionations to ensure that the activity seen was representative of DNA of that size. Quantitative examination of the system shows that, for the lethal event hypothesis to be true, the excision step has to remove an average of 7,000 to 10,000 nucleotides. This figure is so much greater than that seen in other excision processes that alternate hypotheses should be considered. The presently known properties of the hex system can be accounted for by a model invoking the migratory features of type I restriction enzymes."}
{"id": "PMID:1371", "title": "Microcalorimetric study of the anaerobic growth of Escherichia coli: growth thermograms in a synthetic medium.", "content": "A microcalorimetric technique was used for studying the growth of Escherichia coli during anaerobiosis. The growth thermograms obtained are complex and the shape of curves is dependent on the hydrogen lyase activity of the cells. Fermentation balances are given for different culture conditions, and simple growth thermograms are obtained when the hydrogen lyase activity is inhibitied.", "contents": "Microcalorimetric study of the anaerobic growth of Escherichia coli: growth thermograms in a synthetic medium. A microcalorimetric technique was used for studying the growth of Escherichia coli during anaerobiosis. The growth thermograms obtained are complex and the shape of curves is dependent on the hydrogen lyase activity of the cells. Fermentation balances are given for different culture conditions, and simple growth thermograms are obtained when the hydrogen lyase activity is inhibitied."}
{"id": "PMID:1372", "title": "Physiological study of ergot: induction of alkaloid synthesis by tryptophan at the enzymatic level.", "content": "The enhancement of ergot alkaloid production by tryptophan and its analogues in both normal and high-phosphate cultures is more directly related to increased dimethylallyltryptophan (DMAT) synthetase activity rather than to a lack of regulation of the tryptophan biosynthetic enzymes. Thiotryptophan [beta-(1-benzo-thien-3-yl)-alanine] is rather ineffective in the end product regulation of tryptophan biosynthesis, whereas tryptophan and 5-methyltryptophan are potent effectors. The presence of increased levels of DMAT synthetase in ergot cultures supplemented with tryptophan or thiotryptophan, and to a lesser extent with 5-methyltryptophan, suggests that the induction effect involves de novo synthesis of the enzyme. Thiotryptophan and tryptophan but not 5-methyltryptophan can overcome the block of alkaloid synthesis by inorganic phosphate. The results with thiotryptophan indicate that the phosphate effect cannot be explained merely on the basis of a block of tryptophan synthesis.", "contents": "Physiological study of ergot: induction of alkaloid synthesis by tryptophan at the enzymatic level. The enhancement of ergot alkaloid production by tryptophan and its analogues in both normal and high-phosphate cultures is more directly related to increased dimethylallyltryptophan (DMAT) synthetase activity rather than to a lack of regulation of the tryptophan biosynthetic enzymes. Thiotryptophan [beta-(1-benzo-thien-3-yl)-alanine] is rather ineffective in the end product regulation of tryptophan biosynthesis, whereas tryptophan and 5-methyltryptophan are potent effectors. The presence of increased levels of DMAT synthetase in ergot cultures supplemented with tryptophan or thiotryptophan, and to a lesser extent with 5-methyltryptophan, suggests that the induction effect involves de novo synthesis of the enzyme. Thiotryptophan and tryptophan but not 5-methyltryptophan can overcome the block of alkaloid synthesis by inorganic phosphate. The results with thiotryptophan indicate that the phosphate effect cannot be explained merely on the basis of a block of tryptophan synthesis."}
{"id": "PMID:1373", "title": "Microcalorimetric study of the anaerobic growth of Escherichia coli: measurements of the affinity of whole cells for various energy substrates.", "content": "Microcalorimetry has been used to determine the affinity of whole cells of Escherichia coli for glucose, galactose, fructose, and lactose. Anaerobic growth thermograms were analyzed, and the Km and Vmax values for these energy substrates were measured at pH 7.8. Results obtained with this technique using various organisms growing anaerobically on different sugars are compared. This comparison shows that in practically all cases the cellular rate of catabolic activity is a hyperbolic function of the energy substrate concentrations at low sugar concentrations. In some cases this technique also allows determination of kinetics at high sugar concentrations.", "contents": "Microcalorimetric study of the anaerobic growth of Escherichia coli: measurements of the affinity of whole cells for various energy substrates. Microcalorimetry has been used to determine the affinity of whole cells of Escherichia coli for glucose, galactose, fructose, and lactose. Anaerobic growth thermograms were analyzed, and the Km and Vmax values for these energy substrates were measured at pH 7.8. Results obtained with this technique using various organisms growing anaerobically on different sugars are compared. This comparison shows that in practically all cases the cellular rate of catabolic activity is a hyperbolic function of the energy substrate concentrations at low sugar concentrations. In some cases this technique also allows determination of kinetics at high sugar concentrations."}
{"id": "PMID:1374", "title": "Purification and properties of polyol dehydrogenase from Cephalosporium chrysogenus.", "content": "A polyol dehydrogenase of broad specificity was purified 178-fold from extracts of the filamentous fungus Cephalosporium chrysogenum. The enzyme was found to act as an oxido-reductase in two substrate-coenzyme systems: D-sorbitol (or xylitol)-nicotinamide-adenine dinucleotide (NAD) and D-mannitol-nicotinamide adenine dinucleotide phosphate (NADP). The dehydrogenase was composed of five isozymes, which, as a mixture, exhibited these properties: Km to D-sorbitol and D-mannitol, 7.15 to 10(-2) M; PH optimum, 9 to 10; molecular weight, 300,000 subunit weight, 29,000; PI, 5.8 to 7.5. The NADP-linked activity was labile to treatment with heat or ethylenediaminetetraacetic acid. Mixed substrate assays support the hypothesis that both NAD-, and NADP-linked activities are associated with isozymes of a single dehydrogenase.", "contents": "Purification and properties of polyol dehydrogenase from Cephalosporium chrysogenus. A polyol dehydrogenase of broad specificity was purified 178-fold from extracts of the filamentous fungus Cephalosporium chrysogenum. The enzyme was found to act as an oxido-reductase in two substrate-coenzyme systems: D-sorbitol (or xylitol)-nicotinamide-adenine dinucleotide (NAD) and D-mannitol-nicotinamide adenine dinucleotide phosphate (NADP). The dehydrogenase was composed of five isozymes, which, as a mixture, exhibited these properties: Km to D-sorbitol and D-mannitol, 7.15 to 10(-2) M; PH optimum, 9 to 10; molecular weight, 300,000 subunit weight, 29,000; PI, 5.8 to 7.5. The NADP-linked activity was labile to treatment with heat or ethylenediaminetetraacetic acid. Mixed substrate assays support the hypothesis that both NAD-, and NADP-linked activities are associated with isozymes of a single dehydrogenase."}
{"id": "PMID:1375", "title": "Effect of alkali on the structure of cell envelopes of Chlamydia psittaci elementary bodies.", "content": "Suspensions of isolated cell envelopes of infectious elementary bodies (EB) of Chlamydia psittaci at alkaline pH showed a rapid, extensive decrease in absorbance, accompanied by the release of a cell envelope component in a sedimentable form. This phenomenon was observed both at 0 C and with envelopes which had been previously heated to 100 C. Monovalent and divalent cations effectively inhibited the turbidity loss, whereas ethylenediaminetetraacetate (EDTA) caused an accelerated decrease in turbidity. The turbidity loss observed after incubation of the envelopes at alkaline pH could be reversed to the level of the initial value by dialysis against distilled water containing Mg2+. Thin-section electron photomicrographs of purified EB exposed to alkaline buffer with EDTA revealed the loss of the internal contents of cells, but these cells still maintained their round shapes. The cell surface of treated EB appeared pitted in negatively stained preparations, whereas intact EB had a smooth surface. Electron microscopic studies on negatively stained preparations of the clear supernatant obtained after the treatment of the envelope with alkaline buffer containing EDTA demonstrated the presence of spherical particles, approximately 6 to 7 nm in diameter, and rodlike particles, which appeared to be made up of two or more spherical particles.", "contents": "Effect of alkali on the structure of cell envelopes of Chlamydia psittaci elementary bodies. Suspensions of isolated cell envelopes of infectious elementary bodies (EB) of Chlamydia psittaci at alkaline pH showed a rapid, extensive decrease in absorbance, accompanied by the release of a cell envelope component in a sedimentable form. This phenomenon was observed both at 0 C and with envelopes which had been previously heated to 100 C. Monovalent and divalent cations effectively inhibited the turbidity loss, whereas ethylenediaminetetraacetate (EDTA) caused an accelerated decrease in turbidity. The turbidity loss observed after incubation of the envelopes at alkaline pH could be reversed to the level of the initial value by dialysis against distilled water containing Mg2+. Thin-section electron photomicrographs of purified EB exposed to alkaline buffer with EDTA revealed the loss of the internal contents of cells, but these cells still maintained their round shapes. The cell surface of treated EB appeared pitted in negatively stained preparations, whereas intact EB had a smooth surface. Electron microscopic studies on negatively stained preparations of the clear supernatant obtained after the treatment of the envelope with alkaline buffer containing EDTA demonstrated the presence of spherical particles, approximately 6 to 7 nm in diameter, and rodlike particles, which appeared to be made up of two or more spherical particles."}
{"id": "PMID:1376", "title": "Protein-carbohydrate-lipid complex isolated from the cell envelopes of Chlamydia psittaci in alkaline buffer and ethylenediaminetetraacetate.", "content": "Exposure of isolated cell envelopes from purified infectious elementary (EB) of Chlamydia psittaci to sodium carbonate-bicarbonate buffer at pH 10 plus ethylenediaminetetraacetate (EDTA) results in partial solubilization of the total protein. The released materials represent 20% of the dry weight, 16% of the total protein, 40% of the total carbohydrate, and 9% of the total lipid of the cell envelopes. Sucrose density gradient centrifugation, and Sephadex G-200, Sepharose 4B, or diethylaminoethyl-cellulose column chromatography, reveal a protein-carbohydrate-lipid complex of several hundred thousand molecular weight that contains 50% protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the isolated EB cell envelopes reveals two major protein bands, A and B, with estimated molecular masses of approximately 85,000 and 53,000, respectively, both of which also stain for the presence of carbohydrate and lipid. Gel electrophoresis of the protein-carbohydrate-lipid complex reveals two protein bands, C and D, with estimated molecular weights of approximately 17,000 and 13,000, respectively, which contain lipid and a small amount of carbohydrate; bands A and B are not present in the complex. Gel electrophoresis of the cell envelope residues after extraction of the complex with alkali and EDTA shows a single main band, corresponding to the position of band B, which contains protein, carbohydrate, and lipid; band A is completely missing. B and A is believed to be a component of the complex, which is split into two subunits on alkali solubilization.", "contents": "Protein-carbohydrate-lipid complex isolated from the cell envelopes of Chlamydia psittaci in alkaline buffer and ethylenediaminetetraacetate. Exposure of isolated cell envelopes from purified infectious elementary (EB) of Chlamydia psittaci to sodium carbonate-bicarbonate buffer at pH 10 plus ethylenediaminetetraacetate (EDTA) results in partial solubilization of the total protein. The released materials represent 20% of the dry weight, 16% of the total protein, 40% of the total carbohydrate, and 9% of the total lipid of the cell envelopes. Sucrose density gradient centrifugation, and Sephadex G-200, Sepharose 4B, or diethylaminoethyl-cellulose column chromatography, reveal a protein-carbohydrate-lipid complex of several hundred thousand molecular weight that contains 50% protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the isolated EB cell envelopes reveals two major protein bands, A and B, with estimated molecular masses of approximately 85,000 and 53,000, respectively, both of which also stain for the presence of carbohydrate and lipid. Gel electrophoresis of the protein-carbohydrate-lipid complex reveals two protein bands, C and D, with estimated molecular weights of approximately 17,000 and 13,000, respectively, which contain lipid and a small amount of carbohydrate; bands A and B are not present in the complex. Gel electrophoresis of the cell envelope residues after extraction of the complex with alkali and EDTA shows a single main band, corresponding to the position of band B, which contains protein, carbohydrate, and lipid; band A is completely missing. B and A is believed to be a component of the complex, which is split into two subunits on alkali solubilization."}
{"id": "PMID:1377", "title": "Purification and properties of beta-N-acetylglucosaminidase from Escherichia coli.", "content": "beta-N-acetylglucosaminidase (EC 3.2.1.30) has been purified from Escherichia coli K-12 to near homogeneity based on polyacrylamide gel electrophoresis in both 0.5% sodium dodecyl sulfate and in 6 M urea at pH 8.5. The purified enzyme shows a pH optimum of 7.7 and the Km for p-nitrophenyl-beta-D-2-acetamido-2-deoxyglucopyranoside is 0.43 mM. The molecular weight of this enzyme, determined by both Sephadex gel filtration and by sodium dodecyl sulfate gel electrophoresis, is equivalent to 36,000. It is shown to be a soluble cytoplasmic enzyme. Studies on the substrate specificites of the purified enzyme indicate that this enzyme is an exo-beta-N-acetylglucosaminidase.", "contents": "Purification and properties of beta-N-acetylglucosaminidase from Escherichia coli. beta-N-acetylglucosaminidase (EC 3.2.1.30) has been purified from Escherichia coli K-12 to near homogeneity based on polyacrylamide gel electrophoresis in both 0.5% sodium dodecyl sulfate and in 6 M urea at pH 8.5. The purified enzyme shows a pH optimum of 7.7 and the Km for p-nitrophenyl-beta-D-2-acetamido-2-deoxyglucopyranoside is 0.43 mM. The molecular weight of this enzyme, determined by both Sephadex gel filtration and by sodium dodecyl sulfate gel electrophoresis, is equivalent to 36,000. It is shown to be a soluble cytoplasmic enzyme. Studies on the substrate specificites of the purified enzyme indicate that this enzyme is an exo-beta-N-acetylglucosaminidase."}
{"id": "PMID:1378", "title": "Acid protease activity during germination of microcysts of the cellular slime mold Polysphondylium pallidum.", "content": "Extracts of dormant microcysts of Polysphondylium pallidum demonstrate pH optima for the hydrolysis of casein at 3.5 and 6.0. During germination the intracellular pH 6.0 caseinolytic specific activity does not change significantly. The pH 6.0 protease is also active on azo-albumin, revealing the same developmental pattern with this substrate. Both acid protease activities are excreted during the germination process. Addition of purified nonspecific protease to cultures speeds up germination, suggesting that the excreted protease may play a role in removal of the microcyst wall. When cycloheximide is added to cultures, complete germination (emergence) is stopped whereas the pH 6.0 protease activity still accumulates to between 50 and 60% of the maximum control activity. Although this suggests that post-translational controls might mediate the accumulation of a portion of the pH 6.0 protease increase, mixing and dilution experiments with cell extracts do not reveal the differential presence of soluble activators or inhibitors of this activity at different developmental stages. The presence of tightly bound enzyme-inhibitor complexes for protease B in dormant microcysts has not been ruled out and is currently under study.", "contents": "Acid protease activity during germination of microcysts of the cellular slime mold Polysphondylium pallidum. Extracts of dormant microcysts of Polysphondylium pallidum demonstrate pH optima for the hydrolysis of casein at 3.5 and 6.0. During germination the intracellular pH 6.0 caseinolytic specific activity does not change significantly. The pH 6.0 protease is also active on azo-albumin, revealing the same developmental pattern with this substrate. Both acid protease activities are excreted during the germination process. Addition of purified nonspecific protease to cultures speeds up germination, suggesting that the excreted protease may play a role in removal of the microcyst wall. When cycloheximide is added to cultures, complete germination (emergence) is stopped whereas the pH 6.0 protease activity still accumulates to between 50 and 60% of the maximum control activity. Although this suggests that post-translational controls might mediate the accumulation of a portion of the pH 6.0 protease increase, mixing and dilution experiments with cell extracts do not reveal the differential presence of soluble activators or inhibitors of this activity at different developmental stages. The presence of tightly bound enzyme-inhibitor complexes for protease B in dormant microcysts has not been ruled out and is currently under study."}
{"id": "PMID:1379", "title": "Altered nutritional requirements associated with mutations affecting the structures of ribonucleic acid polymerase in Lactobacillus casei.", "content": "Rifampin-resistant mutants were isolated from Lactobacillus casei S1 and examined for possible simultaneous alteration in nutritional properties. Among the 36 mutants obtained either spontaneously or after mutagenesis with 2-aminopurine, 22 were found to be altered with respect to the specific growth requirements. The majority (20 of 22) of the latter mutants were shown to require L-glutamine in addition to the nutrients required by the parental strain for maximal growth, whereas the remaining mutants had apparently lost the requirement for L-aspartate. Further studies with one of the glutamine-requiring mutants revealed that the rifampin resistance of this strain is due to the resistance of ribonucleic acid polymerase itself and that a single mutation is responsible for both rifampin resistance and the glutamine requirement. These results strongly indicate that a structural alteration of the ribonucleic acid polymerase caused by the rifampin resistance mutation somehow affected glutamine metabolism, possibly through change in selective transcription of the genes involved.", "contents": "Altered nutritional requirements associated with mutations affecting the structures of ribonucleic acid polymerase in Lactobacillus casei. Rifampin-resistant mutants were isolated from Lactobacillus casei S1 and examined for possible simultaneous alteration in nutritional properties. Among the 36 mutants obtained either spontaneously or after mutagenesis with 2-aminopurine, 22 were found to be altered with respect to the specific growth requirements. The majority (20 of 22) of the latter mutants were shown to require L-glutamine in addition to the nutrients required by the parental strain for maximal growth, whereas the remaining mutants had apparently lost the requirement for L-aspartate. Further studies with one of the glutamine-requiring mutants revealed that the rifampin resistance of this strain is due to the resistance of ribonucleic acid polymerase itself and that a single mutation is responsible for both rifampin resistance and the glutamine requirement. These results strongly indicate that a structural alteration of the ribonucleic acid polymerase caused by the rifampin resistance mutation somehow affected glutamine metabolism, possibly through change in selective transcription of the genes involved."}
{"id": "PMID:1380", "title": "Preparations and properties of ribonucleic acid polymerase from Acinetobacter calcoaceticus.", "content": "Deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase (EC 2.7.7.6) from Acinetobacter calcoaceticus was purified to apparent homogeneity and its properties were compared with those of the Escherichia coli B enzyme. The molecular weights of the two native active enzymes as well as their alpha and beta subunits appeared to be similar. No subunit corresponding to that of sigma from E. coli was found, and furthermore no separation between the beta subunits could be detected by gel electrophoresis. A number of different DNAs were transcribed by the enzyme from A. calcoaceticus. Maximal RNA synthesis occurred at pH 8.7, 10 mM Mg2+, or 0.3 mM Mn2+ and at a total ionic strength of 0.1. Higher ionic strengths led to increasing inhibition of transcription and at mu = 0.4 complete inhibition was observed. The mechanism of inhibition of salt was not related to the initiation event as observed with T4 core RNA polymerase (R.Kleppe, 1975). In an attempt to understand the mechanism of inhibition by salt, the effect of ionic strength on the sedimentation properties of the enzyme was investigated. At low ionic strength, enzyme species with sedimentation coefficients, s20,w, of 5.8S, 12.4S, and 19.3S were present. In buffers with higher ionic strengths the relative amounts of the 12.4S species decreased. It is suggested, therefore, that the inhibition of activity at higher salt concentrations is caused by a decrease in concentration of the active enzyme species.", "contents": "Preparations and properties of ribonucleic acid polymerase from Acinetobacter calcoaceticus. Deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase (EC 2.7.7.6) from Acinetobacter calcoaceticus was purified to apparent homogeneity and its properties were compared with those of the Escherichia coli B enzyme. The molecular weights of the two native active enzymes as well as their alpha and beta subunits appeared to be similar. No subunit corresponding to that of sigma from E. coli was found, and furthermore no separation between the beta subunits could be detected by gel electrophoresis. A number of different DNAs were transcribed by the enzyme from A. calcoaceticus. Maximal RNA synthesis occurred at pH 8.7, 10 mM Mg2+, or 0.3 mM Mn2+ and at a total ionic strength of 0.1. Higher ionic strengths led to increasing inhibition of transcription and at mu = 0.4 complete inhibition was observed. The mechanism of inhibition of salt was not related to the initiation event as observed with T4 core RNA polymerase (R.Kleppe, 1975). In an attempt to understand the mechanism of inhibition by salt, the effect of ionic strength on the sedimentation properties of the enzyme was investigated. At low ionic strength, enzyme species with sedimentation coefficients, s20,w, of 5.8S, 12.4S, and 19.3S were present. In buffers with higher ionic strengths the relative amounts of the 12.4S species decreased. It is suggested, therefore, that the inhibition of activity at higher salt concentrations is caused by a decrease in concentration of the active enzyme species."}
{"id": "PMID:1381", "title": "Urea-hydrolyzing activity of a T-strain mycoplasma: Ureaplasma urealyticum.", "content": "The urea-hydrolyzing activity of a T-strain mycoplasma was studied in experiments using whole cells and cell-free enzyme preparations by measuring the release of 14CO2 from [14C]urea. Under the conditions used, the urea concentration optimum is approximately 5.6 X 10(-3) M urea. The activity is soluble and not membrane bound. It is stable at -70 C for several weeks but is more labile at higher temperatures. The pH optimum is between 5.0 and 6.0. The effect of several inhibitors on the activity was tested and revealed similarities, as well as differences, between T-strain mycoplasma urease activity and the urease activity of other organisms and plants.", "contents": "Urea-hydrolyzing activity of a T-strain mycoplasma: Ureaplasma urealyticum. The urea-hydrolyzing activity of a T-strain mycoplasma was studied in experiments using whole cells and cell-free enzyme preparations by measuring the release of 14CO2 from [14C]urea. Under the conditions used, the urea concentration optimum is approximately 5.6 X 10(-3) M urea. The activity is soluble and not membrane bound. It is stable at -70 C for several weeks but is more labile at higher temperatures. The pH optimum is between 5.0 and 6.0. The effect of several inhibitors on the activity was tested and revealed similarities, as well as differences, between T-strain mycoplasma urease activity and the urease activity of other organisms and plants."}
{"id": "PMID:1382", "title": "Arginine decarboxylase from a Pseudomonas species.", "content": "An arginine decarboxylase has been isolated from a Pseudomonas species. The enzyme is constitutive and did not appear to be repressed by a variety of carbon sources. After an approximately 40-fold purification, the enzyme appeared more similar in its properties to the Escherichia coli biosynthetic arginine decarboxylase than to the E. coli inducible (biodegradative) enzyme. The Pseudomonas arginine decarboxylase exhibited a pH optimum of 8.1 and an absolute requirement of Mg2+ and pyridoxal phosphate, and was inhibited significantly at lower Mg2+ concentrations by the polyamines putrescine, spermidine, and cadaverine. The Km for L-arginine was about 0.25 mM at pH 8.1 AND 7.2. The enzyme was completely inhibited by p-chloromercuribenzoate. The inhibition was prevented by dithiothreitol, a feature that suggests the involvement of an -SH group. Of a variety of labeled amino acids tested, only L-arginine, but not D-arginine was decarboxylated. D-Arginine was a potent inhibitor of arginine decarboxylase with a Ki of 3.2 muM.", "contents": "Arginine decarboxylase from a Pseudomonas species. An arginine decarboxylase has been isolated from a Pseudomonas species. The enzyme is constitutive and did not appear to be repressed by a variety of carbon sources. After an approximately 40-fold purification, the enzyme appeared more similar in its properties to the Escherichia coli biosynthetic arginine decarboxylase than to the E. coli inducible (biodegradative) enzyme. The Pseudomonas arginine decarboxylase exhibited a pH optimum of 8.1 and an absolute requirement of Mg2+ and pyridoxal phosphate, and was inhibited significantly at lower Mg2+ concentrations by the polyamines putrescine, spermidine, and cadaverine. The Km for L-arginine was about 0.25 mM at pH 8.1 AND 7.2. The enzyme was completely inhibited by p-chloromercuribenzoate. The inhibition was prevented by dithiothreitol, a feature that suggests the involvement of an -SH group. Of a variety of labeled amino acids tested, only L-arginine, but not D-arginine was decarboxylated. D-Arginine was a potent inhibitor of arginine decarboxylase with a Ki of 3.2 muM."}
{"id": "PMID:1383", "title": "Derepression of certain aromatic amino acid biosynthetic enzymes of Escherichia coli K-12 by growth in Fe3+-deficient medium.", "content": "3-Deoxy-arabino-heptulosonic acid 7-phosphate synthase, prephenate dehydratase, tryptophan synthase, and 2,3-dihydroxybenzoylserine synthase enzyme activities are derepressed in wild-type Escherichia coli K-12 cells grown on Fe3+-deficient medium. This derepression is reversed when FeSO4 is added to the growth medium. Addition of shikimic acid to the Fe3+-deficient growth medium caused repression of the first three enzyme activities but not of 2,3-dihydroxybenzoylserine synthase activity. Addition of 2,3-dihydroxybenzoic acid to the Fe3+-deficient growth medium has no effect on any of the above-mentioned enzyme activities. The Fe3+ deficiency-mediated derepression of 3-deoxyarabino-heptulosonic acid 7-phosphate synthase activity is due to an elevation of the tyrosine-sensitive isoenzyme; the phenylalanine-sensitive isoenzyme is not derepressed under these conditions.", "contents": "Derepression of certain aromatic amino acid biosynthetic enzymes of Escherichia coli K-12 by growth in Fe3+-deficient medium. 3-Deoxy-arabino-heptulosonic acid 7-phosphate synthase, prephenate dehydratase, tryptophan synthase, and 2,3-dihydroxybenzoylserine synthase enzyme activities are derepressed in wild-type Escherichia coli K-12 cells grown on Fe3+-deficient medium. This derepression is reversed when FeSO4 is added to the growth medium. Addition of shikimic acid to the Fe3+-deficient growth medium caused repression of the first three enzyme activities but not of 2,3-dihydroxybenzoylserine synthase activity. Addition of 2,3-dihydroxybenzoic acid to the Fe3+-deficient growth medium has no effect on any of the above-mentioned enzyme activities. The Fe3+ deficiency-mediated derepression of 3-deoxyarabino-heptulosonic acid 7-phosphate synthase activity is due to an elevation of the tyrosine-sensitive isoenzyme; the phenylalanine-sensitive isoenzyme is not derepressed under these conditions."}
{"id": "PMID:1384", "title": "Control of differentiation in streptomycetes: involvement of extrachromosomal deoxyribonucleic acid and glucose repression in aerial mycelia development.", "content": "When Streptomyces alboniger spores were grown in Hickey-Tresner broth containing 5 muM ethidium bromide, a high frequency of permanently cured aerial mycelia-negative (am-) colonies was recovered. The appearance an am- colonies was time dependent: a very low frequency (0.3%) at zero time, a maximum (9 to 21%) after 2 to 5 days of growth, and a decline again to low frequencies later in the growth cycle. On agar, cured am- colonies of S. alboniger still produced puromycin. The development of aerial mycelia in S. alboniger, S. scabies, and S. coelicolor was also sensitive to glucose repression. Colonies grown on Hickey-Tresner agar containing 2% glucose remained phenotypically am- throughout the observation period. Adenine (2.5 mM or greater), and to a lesser extent adenosine and guanosine, specifically reversed the repression. The accumulation of undissociated organic acids appears to be involved in glucose repression of aerial mycelia formation. However, this does not appear to be the case with puromycin production in S. alboniger; glucose repression was observed over the pH range 5.0 to 7.5.", "contents": "Control of differentiation in streptomycetes: involvement of extrachromosomal deoxyribonucleic acid and glucose repression in aerial mycelia development. When Streptomyces alboniger spores were grown in Hickey-Tresner broth containing 5 muM ethidium bromide, a high frequency of permanently cured aerial mycelia-negative (am-) colonies was recovered. The appearance an am- colonies was time dependent: a very low frequency (0.3%) at zero time, a maximum (9 to 21%) after 2 to 5 days of growth, and a decline again to low frequencies later in the growth cycle. On agar, cured am- colonies of S. alboniger still produced puromycin. The development of aerial mycelia in S. alboniger, S. scabies, and S. coelicolor was also sensitive to glucose repression. Colonies grown on Hickey-Tresner agar containing 2% glucose remained phenotypically am- throughout the observation period. Adenine (2.5 mM or greater), and to a lesser extent adenosine and guanosine, specifically reversed the repression. The accumulation of undissociated organic acids appears to be involved in glucose repression of aerial mycelia formation. However, this does not appear to be the case with puromycin production in S. alboniger; glucose repression was observed over the pH range 5.0 to 7.5."}
{"id": "PMID:1385", "title": "Studies on cytochrome oxidase. Partial resolution of enzymes containing seven or six subunits, from yeast and beef heart, respectively.", "content": "Highly active, essentially homogeneous, preparations of ferrocytochrome c oxidase (EC 1.9.3.1) have been obtained from both yeast and beef heart by extraction with cholate, fractionation with ammonium sulfate, and replacement of cholate by Tween 20. The molecular weights of the resultant proteins equal 260 +/- 23 X 10(3) and 205 +/- 10(3); they contain seven and six different polypeptide subunits, respectively, all in equimolar amounts, with apparent molecular weights of 42.4, 34.1, 24.7, 14.6, 14.6, 12.3, 10.6 X 10(3), and 47.5, 20.4, 14.5, 14.5, 13.0, 11.0 X 10(3), respectively. By means of apolar chromatography on L-leucine coupled to agarose these enzymes can be stripped of their largest subunit(s) resulting in preparations with molecular weights of 170 +/- 17 X 10(3) and 124 +/- 20 X 10(3), and containing only five polypeptides, with the largest remaining one (molecular weight congruent to 20 X 10(3)) present in less than stoichiometric amounts. This interconversion and subunit removal has been monitored by exclusion chromatography, four systems of acrylamide gel electrophoresis--some with the protein labeled with 125I under denaturing conditions--isoelectric focusing, and hydrodynamic methods. It has virtually no effect on heme a and copper content and on the catalytic parameters of the enzymes.  We conclude that subunits I and II in enzymes from fungal, and subunit I in those from animal, sources are dispensable for the catalysis of the oxidation of ferrocytochrome c by, and are probably not essential for the attatchment of prosthetic groups to, these proteins.", "contents": "Studies on cytochrome oxidase. Partial resolution of enzymes containing seven or six subunits, from yeast and beef heart, respectively. Highly active, essentially homogeneous, preparations of ferrocytochrome c oxidase (EC 1.9.3.1) have been obtained from both yeast and beef heart by extraction with cholate, fractionation with ammonium sulfate, and replacement of cholate by Tween 20. The molecular weights of the resultant proteins equal 260 +/- 23 X 10(3) and 205 +/- 10(3); they contain seven and six different polypeptide subunits, respectively, all in equimolar amounts, with apparent molecular weights of 42.4, 34.1, 24.7, 14.6, 14.6, 12.3, 10.6 X 10(3), and 47.5, 20.4, 14.5, 14.5, 13.0, 11.0 X 10(3), respectively. By means of apolar chromatography on L-leucine coupled to agarose these enzymes can be stripped of their largest subunit(s) resulting in preparations with molecular weights of 170 +/- 17 X 10(3) and 124 +/- 20 X 10(3), and containing only five polypeptides, with the largest remaining one (molecular weight congruent to 20 X 10(3)) present in less than stoichiometric amounts. This interconversion and subunit removal has been monitored by exclusion chromatography, four systems of acrylamide gel electrophoresis--some with the protein labeled with 125I under denaturing conditions--isoelectric focusing, and hydrodynamic methods. It has virtually no effect on heme a and copper content and on the catalytic parameters of the enzymes.  We conclude that subunits I and II in enzymes from fungal, and subunit I in those from animal, sources are dispensable for the catalysis of the oxidation of ferrocytochrome c by, and are probably not essential for the attatchment of prosthetic groups to, these proteins."}
{"id": "PMID:1386", "title": "Isolation and characterization of crystalline methylglyoxal synthetase from Proteus vulgaris.", "content": "Methylglyoxal synthetase, which catalyzes the conversion of dihydroxyacetone phosphate to methylglyoxal and inorganic phosphate, has been isolated and crystalized in good yields from Proteus vulgaris. The enzyme was shown to be homogeneous by a variety of criteria and was found to be a dimer (Mr = 135,000; s20,w = 7.2 S) composed of two apparently identical catalytic and physical properties and their interconvertible nature suggest that they do not represent true isozymes. The enzyme is specific for dihydroxyacetone phosphate and does not form methylglyoxal from glyceraldehyde 3-phophate, glyceraldehyde, or dihydroxyacetone. Nonphosphorylated analogs are neither substrates nor competive inhibitors, but a variety of phosphorylated analogs are competitive with respect to dihydroxyacetone phosphate. The enzyme is inhibited by inorganic orthophosphate in a complex manner which is overcome by dihydroxyacetone phosphate in a signoidal manner", "contents": "Isolation and characterization of crystalline methylglyoxal synthetase from Proteus vulgaris. Methylglyoxal synthetase, which catalyzes the conversion of dihydroxyacetone phosphate to methylglyoxal and inorganic phosphate, has been isolated and crystalized in good yields from Proteus vulgaris. The enzyme was shown to be homogeneous by a variety of criteria and was found to be a dimer (Mr = 135,000; s20,w = 7.2 S) composed of two apparently identical catalytic and physical properties and their interconvertible nature suggest that they do not represent true isozymes. The enzyme is specific for dihydroxyacetone phosphate and does not form methylglyoxal from glyceraldehyde 3-phophate, glyceraldehyde, or dihydroxyacetone. Nonphosphorylated analogs are neither substrates nor competive inhibitors, but a variety of phosphorylated analogs are competitive with respect to dihydroxyacetone phosphate. The enzyme is inhibited by inorganic orthophosphate in a complex manner which is overcome by dihydroxyacetone phosphate in a signoidal manner"}
{"id": "PMID:1387", "title": "Beef kidney 3-hydroxyanthranilic acid oxygenase. Purification, characterization, and analysis of the assay.", "content": "Beef kidney 3-hydroxyanthranilic acid oxygenase has been purified to homogeneity. It is a single subunit protein of Mr = 34,000 +/- 2,000 with a frictional coefficient (f/f0) of about 1.1. The enzyme readily aggregates to form, apparently inactive, higher molecular weight oligomers. The very rapid loss of enzyme activity during the assay was analyzed extensively. It was found to be due to inactivation of the enzyme by the substrate, 3-hydroxyanthranilate, and unrelated to enzyme turnover or oxidation of bound iron. The loss of activity was shown to be a first order decay process, and methods are given for obtaining accurate initial reaction rates under all conditions. Evidence was presented that the enzyme assumes a catalytically inactive conformation at pH 3.4, which only relatively slowly rearranges to an active form at pH 6.5; the rearrangement can be blocked by the presence of substrate. We have found that Fe2+, which is required for enzymatic activity, can equilibrate freely, albeit slowly, with the enzyme during the course of the enzyme reaction even in the presence of saturating 3-hydroxanthranilate. Under assay conditons, the Fe2+ has an apparent dissociation constant of 0.04 mM. The kinetic properties of the enzyme were found to be dramatically different in beta,beta-dimethylglutarate buffer and collidine buffer; both the rate of loss of activity during the assay and the substrate Km and Vmax were affected.", "contents": "Beef kidney 3-hydroxyanthranilic acid oxygenase. Purification, characterization, and analysis of the assay. Beef kidney 3-hydroxyanthranilic acid oxygenase has been purified to homogeneity. It is a single subunit protein of Mr = 34,000 +/- 2,000 with a frictional coefficient (f/f0) of about 1.1. The enzyme readily aggregates to form, apparently inactive, higher molecular weight oligomers. The very rapid loss of enzyme activity during the assay was analyzed extensively. It was found to be due to inactivation of the enzyme by the substrate, 3-hydroxyanthranilate, and unrelated to enzyme turnover or oxidation of bound iron. The loss of activity was shown to be a first order decay process, and methods are given for obtaining accurate initial reaction rates under all conditions. Evidence was presented that the enzyme assumes a catalytically inactive conformation at pH 3.4, which only relatively slowly rearranges to an active form at pH 6.5; the rearrangement can be blocked by the presence of substrate. We have found that Fe2+, which is required for enzymatic activity, can equilibrate freely, albeit slowly, with the enzyme during the course of the enzyme reaction even in the presence of saturating 3-hydroxanthranilate. Under assay conditons, the Fe2+ has an apparent dissociation constant of 0.04 mM. The kinetic properties of the enzyme were found to be dramatically different in beta,beta-dimethylglutarate buffer and collidine buffer; both the rate of loss of activity during the assay and the substrate Km and Vmax were affected."}
{"id": "PMID:1388", "title": "Effects of colipase and taurodeoxycholate on the catalytic and physical properties of pancreatic lipase B at an oil water interface.", "content": "A monolayer reaction system employing tripropionin and siliconized glass beads was used to study the effects of taurodeoxycholate and colipase on the catalytic activity, interfacial stability, and interfacial affinity of porcine pancreatic lipase B (EC 3.1.1.3) The stability and catalytic activity of lipase at the bead-water interface are governed by the same two ionizable groups with pKa values (in the absence of cofactors) of 5.6 and 9.3. Colipase alone or with bile salt caused only a slight perturbation of these values. At low concentrations, 0 to 0.3mM, taurodeoxycholate increases the stability of lipase by 5-fold. At higher concentrations, 0.3 to 0.8 mM, but still below its critical micelle concentration, taurodeoxycholate prevents the adsorption of lipase to the bead-water interface. This appears to be the major mechanism by which this bile salt inhibits lipolysis. Colipase exerts small positive effects on lipase stability and catalytic activity. More importantly, colipase enables the adsorption of lipase in the presence of bile salt, thereby reversing the inhibition.", "contents": "Effects of colipase and taurodeoxycholate on the catalytic and physical properties of pancreatic lipase B at an oil water interface. A monolayer reaction system employing tripropionin and siliconized glass beads was used to study the effects of taurodeoxycholate and colipase on the catalytic activity, interfacial stability, and interfacial affinity of porcine pancreatic lipase B (EC 3.1.1.3) The stability and catalytic activity of lipase at the bead-water interface are governed by the same two ionizable groups with pKa values (in the absence of cofactors) of 5.6 and 9.3. Colipase alone or with bile salt caused only a slight perturbation of these values. At low concentrations, 0 to 0.3mM, taurodeoxycholate increases the stability of lipase by 5-fold. At higher concentrations, 0.3 to 0.8 mM, but still below its critical micelle concentration, taurodeoxycholate prevents the adsorption of lipase to the bead-water interface. This appears to be the major mechanism by which this bile salt inhibits lipolysis. Colipase exerts small positive effects on lipase stability and catalytic activity. More importantly, colipase enables the adsorption of lipase in the presence of bile salt, thereby reversing the inhibition."}
{"id": "PMID:1389", "title": "Rickettsial permeability. An ADP-ATP transport system.", "content": "The obligate intracellular parasitic bacterium, Rickettsia prowazeki, has a carrier-mediated transport system for ADP and ATP. The transport of nucleotides was measured by membrane filtration assays; the assay was shown not to harm the relatively labile rickettsiae. The nucleotide transport system was shown to reside in the rickettsiae, not in the contaminating yolk sac mitochondria of the preparation. The influx of nucleotide had an activation energy of 12 to 13 kcal above 22 deg-rees (an apparent transition temperature), and 30 kcal below this value. The uptake of nucleotide was independent of the Mg2+ concentration, but was markedly stimulated by the phosphate concentration. The pH optimum of the influx of nucleotide was pH 7. The specificity of the transport system was remarkable in that it required a specific moiety in each portion of the nucleotide, i.e. an adenine base, a ribose sugar, and two or three, but not one, phosphates. Of the wide variety of compounds tested, the system could transport only ADP, ATP, and (beta, gamma-methylene) adenosine 5'-triphosphate. The influx of nucleotide was a saturable process; half-maximum velocity was achieved at a nucleotide concentration of about 75 muM. ADP and ATP were competitive inhibitors of each other's transport. Although at least 95% of the labeled intracellular nucleotide was exchangeable, efflux of labeled nucleotide was observed only in the presence of unlabeled nucleotide in the medium. Half-maximum efflux was achieved at a concentration of about 75 muM. A large intracellular to extracellular concentration gradient of labeled nucleotide was maintained in the presence of metabolic inhibitors and uncouplers, which completely abolished rickettsial hemolysis. While having no effect on the steady state, KCN and DNP accelerated both influx and efflux. Measurements of the endogenous pool of adenine nucleotides in isolated rickettsiae show that is was large (5 mM), and that these unlabeled nucleotides exchanged, on approximately a 1/1 basis, with exogenously added nucleotide. These studies support the proposal that rickettsiae are not \"leaky\" to adenine nucleotides or to small molecules in general, and that they have a carrier-mediated transport system which allows an exchange of host and parasite ADP and ATP.", "contents": "Rickettsial permeability. An ADP-ATP transport system. The obligate intracellular parasitic bacterium, Rickettsia prowazeki, has a carrier-mediated transport system for ADP and ATP. The transport of nucleotides was measured by membrane filtration assays; the assay was shown not to harm the relatively labile rickettsiae. The nucleotide transport system was shown to reside in the rickettsiae, not in the contaminating yolk sac mitochondria of the preparation. The influx of nucleotide had an activation energy of 12 to 13 kcal above 22 deg-rees (an apparent transition temperature), and 30 kcal below this value. The uptake of nucleotide was independent of the Mg2+ concentration, but was markedly stimulated by the phosphate concentration. The pH optimum of the influx of nucleotide was pH 7. The specificity of the transport system was remarkable in that it required a specific moiety in each portion of the nucleotide, i.e. an adenine base, a ribose sugar, and two or three, but not one, phosphates. Of the wide variety of compounds tested, the system could transport only ADP, ATP, and (beta, gamma-methylene) adenosine 5'-triphosphate. The influx of nucleotide was a saturable process; half-maximum velocity was achieved at a nucleotide concentration of about 75 muM. ADP and ATP were competitive inhibitors of each other's transport. Although at least 95% of the labeled intracellular nucleotide was exchangeable, efflux of labeled nucleotide was observed only in the presence of unlabeled nucleotide in the medium. Half-maximum efflux was achieved at a concentration of about 75 muM. A large intracellular to extracellular concentration gradient of labeled nucleotide was maintained in the presence of metabolic inhibitors and uncouplers, which completely abolished rickettsial hemolysis. While having no effect on the steady state, KCN and DNP accelerated both influx and efflux. Measurements of the endogenous pool of adenine nucleotides in isolated rickettsiae show that is was large (5 mM), and that these unlabeled nucleotides exchanged, on approximately a 1/1 basis, with exogenously added nucleotide. These studies support the proposal that rickettsiae are not \"leaky\" to adenine nucleotides or to small molecules in general, and that they have a carrier-mediated transport system which allows an exchange of host and parasite ADP and ATP."}
{"id": "PMID:1390", "title": "Monomeric purine nucleoside phosphorylase from rabbit liver. Purification and characterization.", "content": "Rabbit liver purine nucleoside phosphorylase (purine nucleoside: orthophosphate ribosyltransferase EC 2.4.2.1.) was purified to homogeneity by column chromatography and ammonium sulfate fractionation. Homogeneity was established by disc gel electrophoresis in presence and absence of sodium dodecyl sulfate, and isoelectric focusing. Molecular weights of 46,000 and 39,000 were determined, respectively, by gel filtration and by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis. Product inhibition was observed with guanine and hypoxanthine as strong competitive inhibitors for the enzymatic phosphorolysis of guanosine. Respective Kis calculated were 1.25 x 10(-5) M for guanine and 2.5 x 10(-5) M for hypoxanthine. Ribose 1-phosphate, another product of the reaction, gave noncompetitive inhibition with guanosine as variable substrate, and an inhibition constant of 3.61 x 10(-4) M was calculated. The protection of essential --SH groups on the enzyme, by 2-mercaptoethanol or dithiothreitol, was necessary for the maintenance of enzyme activity. Noncompetitive inhibition was observed for p-chloromercuribenzoate with an inhibition constant of 5.68 x 10(-6)M. Complete reversal of this inhibition by an excess of 2-mercaptoethanol or dithiothreitol was demonstrated. In the presence of methylene blue, the enzyme showed a high sensitivity to photooxidation and a dependence of photoinactivation on pH, strongly implicating histidine as the susceptible group at the active site of the enzyme. The pKa values determined for ionizable groups of the active site of the enzyme were near pH 5.5 and pH 8.5 The chemical and kinetic evidences suggest that histidine and cysteine may be essential for catalysis. Inorganic orthophosphate (Km 1.54 x 10(-2) M) was an obligatory anion requirement, and arsenate substituted for phosphate with comparable results. Guanosine (Km 5.00 x 10(-5) M), deoxyguanosine (Km 1.00 x 10(-4)M) and inosine (Km 1.33 x 10(-4)M), were substrates for enzymatic phosphorolysis. Xanthosine was an extremely poor substrate, and adenosine was not phosphorylyzed at 20-fold excess of the homogeneous enzyme. Guanine (Km 1.82 x 10(-5)M),ribose 1-phosphate (Km 1.34 x 10(-4) M) and hypoxanthine were substrates for the reverse reaction, namely, the enzymatic synthesis of nucleosides. The initial velocity studies of the saturation of the enzyme with guanosine, at various fixed concentrations of inorganic orthophosphate, suggest a sequential bireactant catalytic mechanism for the enzyme.", "contents": "Monomeric purine nucleoside phosphorylase from rabbit liver. Purification and characterization. Rabbit liver purine nucleoside phosphorylase (purine nucleoside: orthophosphate ribosyltransferase EC 2.4.2.1.) was purified to homogeneity by column chromatography and ammonium sulfate fractionation. Homogeneity was established by disc gel electrophoresis in presence and absence of sodium dodecyl sulfate, and isoelectric focusing. Molecular weights of 46,000 and 39,000 were determined, respectively, by gel filtration and by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis. Product inhibition was observed with guanine and hypoxanthine as strong competitive inhibitors for the enzymatic phosphorolysis of guanosine. Respective Kis calculated were 1.25 x 10(-5) M for guanine and 2.5 x 10(-5) M for hypoxanthine. Ribose 1-phosphate, another product of the reaction, gave noncompetitive inhibition with guanosine as variable substrate, and an inhibition constant of 3.61 x 10(-4) M was calculated. The protection of essential --SH groups on the enzyme, by 2-mercaptoethanol or dithiothreitol, was necessary for the maintenance of enzyme activity. Noncompetitive inhibition was observed for p-chloromercuribenzoate with an inhibition constant of 5.68 x 10(-6)M. Complete reversal of this inhibition by an excess of 2-mercaptoethanol or dithiothreitol was demonstrated. In the presence of methylene blue, the enzyme showed a high sensitivity to photooxidation and a dependence of photoinactivation on pH, strongly implicating histidine as the susceptible group at the active site of the enzyme. The pKa values determined for ionizable groups of the active site of the enzyme were near pH 5.5 and pH 8.5 The chemical and kinetic evidences suggest that histidine and cysteine may be essential for catalysis. Inorganic orthophosphate (Km 1.54 x 10(-2) M) was an obligatory anion requirement, and arsenate substituted for phosphate with comparable results. Guanosine (Km 5.00 x 10(-5) M), deoxyguanosine (Km 1.00 x 10(-4)M) and inosine (Km 1.33 x 10(-4)M), were substrates for enzymatic phosphorolysis. Xanthosine was an extremely poor substrate, and adenosine was not phosphorylyzed at 20-fold excess of the homogeneous enzyme. Guanine (Km 1.82 x 10(-5)M),ribose 1-phosphate (Km 1.34 x 10(-4) M) and hypoxanthine were substrates for the reverse reaction, namely, the enzymatic synthesis of nucleosides. The initial velocity studies of the saturation of the enzyme with guanosine, at various fixed concentrations of inorganic orthophosphate, suggest a sequential bireactant catalytic mechanism for the enzyme."}
{"id": "PMID:1391", "title": "Purification to homogeneity and properties of two D-alanine carboxypeptidases I From Escherichia coli.", "content": "Three homogeneous preparations of D-alanine carboxypeptidases I have been obtained from Escherichia coli strain H2143, termed enzymes IA, IB, and IC. Enzyme IA purified from the membrane after extraction with Triton X-100 appeared on sodium dodecyl sulfate gel electrophoresis to be a polypeptide doublet whose monomer molecular weights were about 32,000 and 34,000. In addition to D-alanine carboxypeptidase activity, it catalyzed a transpeptidase reaction with several substrates, bound [14C]penicillin G, had a weak penicillinase activity, but was devoid of endopeptidase activity. Enzyme IB obtained from the membrane after LiCl extraction and enzyme IC obtained from the supernatant solution were either identical or extremely similar. They were composed of a single polypeptide whose monomer molecular weight was about 41,000. In addition to carboxypeptidase activity, they catalyzed an endopeptidase reaction, had weak penicillinase activity, and had very poor transpeptidase activity, but did not bind [14C]penicillin G. Some data relating to the mechanism of catalysis by these enzymes are described. Their possible physiological role is discussed.", "contents": "Purification to homogeneity and properties of two D-alanine carboxypeptidases I From Escherichia coli. Three homogeneous preparations of D-alanine carboxypeptidases I have been obtained from Escherichia coli strain H2143, termed enzymes IA, IB, and IC. Enzyme IA purified from the membrane after extraction with Triton X-100 appeared on sodium dodecyl sulfate gel electrophoresis to be a polypeptide doublet whose monomer molecular weights were about 32,000 and 34,000. In addition to D-alanine carboxypeptidase activity, it catalyzed a transpeptidase reaction with several substrates, bound [14C]penicillin G, had a weak penicillinase activity, but was devoid of endopeptidase activity. Enzyme IB obtained from the membrane after LiCl extraction and enzyme IC obtained from the supernatant solution were either identical or extremely similar. They were composed of a single polypeptide whose monomer molecular weight was about 41,000. In addition to carboxypeptidase activity, they catalyzed an endopeptidase reaction, had weak penicillinase activity, and had very poor transpeptidase activity, but did not bind [14C]penicillin G. Some data relating to the mechanism of catalysis by these enzymes are described. Their possible physiological role is discussed."}
{"id": "PMID:1392", "title": "Effects of p-hydroxymercuribenzoate binding on the visible absorption spectrum of methemoglobin.", "content": "The binding of p-hydroxymercuribenzoate to human methemoglobin causes a perturbation of the visible heme abosrption spectrum which is expressed by an increase in absorbance in the high spin band regions, 480 to 510 nm and 590 to 640 nm, concomitant with a decrease in absorbance in the alpha- and beta-band absorption regions. The pH dependence of the p-hydroxymercuribenzoate-induced difference spectrum can be accounted for quantitatively by a 5% shift toward higher spin of the aquo form of methemoglobin, a 15% shift toward higher spin of the hydroxide form, and a shift in the apparent pKa for the water to hydroxide transition from 7.92 to 8.04 when mercurial is bound. The rate of these heme abosrbance changes is consistent with the rapid second order formation of the beta93 cysteine, mercury-mercaptide bond and does not represent a change due to the dissociation of methemoglobin tetramers into dimers, even though the latter, slow process does follow mercurial binding. The observation of an increase in spin produced by the binding of a reagent which also promotes dimer formation argues strongly against any direct correlation between an increase in spin and the appearance of deoxyhemoglobin-like conformations.", "contents": "Effects of p-hydroxymercuribenzoate binding on the visible absorption spectrum of methemoglobin. The binding of p-hydroxymercuribenzoate to human methemoglobin causes a perturbation of the visible heme abosrption spectrum which is expressed by an increase in absorbance in the high spin band regions, 480 to 510 nm and 590 to 640 nm, concomitant with a decrease in absorbance in the alpha- and beta-band absorption regions. The pH dependence of the p-hydroxymercuribenzoate-induced difference spectrum can be accounted for quantitatively by a 5% shift toward higher spin of the aquo form of methemoglobin, a 15% shift toward higher spin of the hydroxide form, and a shift in the apparent pKa for the water to hydroxide transition from 7.92 to 8.04 when mercurial is bound. The rate of these heme abosrbance changes is consistent with the rapid second order formation of the beta93 cysteine, mercury-mercaptide bond and does not represent a change due to the dissociation of methemoglobin tetramers into dimers, even though the latter, slow process does follow mercurial binding. The observation of an increase in spin produced by the binding of a reagent which also promotes dimer formation argues strongly against any direct correlation between an increase in spin and the appearance of deoxyhemoglobin-like conformations."}
{"id": "PMID:1393", "title": "Binding of inositol hexaphosphate to human methemoglobin.", "content": "The observed static difference spectrum produced by inositol hexaphosphate binding to methemoglobin is the sum of a very fast and a slow spectral transition. The more rapid absorbance change is too fast to be measured by stopped flow techniques, whereas the slow change exhibits a half-time in the range 1 to 6 s. From the pH dependence of the rapidly formed difference spectrum and from a series of heme ligand binding studies, the rapid phase is interpreted to reflect a localized tertiary conformational change which immediately accompanies inositol hexaphosphate binding and results in a selective increase in spin and reactivity of the beta chain heme groups. In contrast, the slow phase appears to reflect a first order isomerization process which involves only a small portion (less than 10%) of the hemoglobin molecules and results primarily in a marked alteration of the spectral properties of the alpha chains with little change in spin. While the rapid spectral transition cannot be directly related to the overall quaternary transition which occurs during oxygen binding to ferrous deoxyhemoglobin, the slow spectral transition may represent the abortive formation of a deoxyhemoglobin A-like conformation which is inhibited in both rate and extent by the presence of water molecules bound to the heme iron atoms.", "contents": "Binding of inositol hexaphosphate to human methemoglobin. The observed static difference spectrum produced by inositol hexaphosphate binding to methemoglobin is the sum of a very fast and a slow spectral transition. The more rapid absorbance change is too fast to be measured by stopped flow techniques, whereas the slow change exhibits a half-time in the range 1 to 6 s. From the pH dependence of the rapidly formed difference spectrum and from a series of heme ligand binding studies, the rapid phase is interpreted to reflect a localized tertiary conformational change which immediately accompanies inositol hexaphosphate binding and results in a selective increase in spin and reactivity of the beta chain heme groups. In contrast, the slow phase appears to reflect a first order isomerization process which involves only a small portion (less than 10%) of the hemoglobin molecules and results primarily in a marked alteration of the spectral properties of the alpha chains with little change in spin. While the rapid spectral transition cannot be directly related to the overall quaternary transition which occurs during oxygen binding to ferrous deoxyhemoglobin, the slow spectral transition may represent the abortive formation of a deoxyhemoglobin A-like conformation which is inhibited in both rate and extent by the presence of water molecules bound to the heme iron atoms."}
{"id": "PMID:1394", "title": "Molecular size of nerve growth factor in dilute solution.", "content": "Nerve growth factor (NGF) is a protein composed of two identical chains of mass 13,259. An analysis of the sedimentation equilibrium, sedimentation velocity, and gel filtration behavior of dilute solutions of NGF indicates the existence of a rapidly reversible monomer in equilibrium dimer equilibrium and that the association constant K for the reaction at neutral pH is 9.4 X 10(6)M-1. Reaction mixtures consist of equal concentrations of monomer and dimer at a total protein concentration as high as 1.4 mug/ml, and at 1 ng/ml, monomer accounts for greater than 99% of the total. The latter concentration is 20 to 30 times that required for the biological activity of NGF. Several lines of evidence suggest that the dimerization reaction is highly stereospecific, although its biological significance is not known.", "contents": "Molecular size of nerve growth factor in dilute solution. Nerve growth factor (NGF) is a protein composed of two identical chains of mass 13,259. An analysis of the sedimentation equilibrium, sedimentation velocity, and gel filtration behavior of dilute solutions of NGF indicates the existence of a rapidly reversible monomer in equilibrium dimer equilibrium and that the association constant K for the reaction at neutral pH is 9.4 X 10(6)M-1. Reaction mixtures consist of equal concentrations of monomer and dimer at a total protein concentration as high as 1.4 mug/ml, and at 1 ng/ml, monomer accounts for greater than 99% of the total. The latter concentration is 20 to 30 times that required for the biological activity of NGF. Several lines of evidence suggest that the dimerization reaction is highly stereospecific, although its biological significance is not known."}
{"id": "PMID:1395", "title": "Carbon 13 resonances of 13CO2 carbamino adducts of alpha and beta chains in human adult hemoglobin.", "content": "The principal component of normal adult human hemoglobin Ao, was equilibrated under various conditions with 13CO2. In addition, derivatives containing specifically carbamylated NH2-terinal groups in alpha or beta chains, or both, were prepared by treatment with cyanate, and equilibrated likewise to allow the identification of specific resonances observed by 13C nuclear magnetic resonance. In deoxyhemoglobin, a resonanance at 29.2 ppm upfield of external CS2 was assigned to the alpha chain terminal adduct, and one at 29.8 ppm to the beta chain terminal adduct. In the liganded state as the CO derivative, the terminal adduct on both chains showed a common resonance position at 29.8 ppm. Small effects of pH on the resonance positions were observed. Under certain conditions, a resonance was observed at 33.4 ppm, probably not ascribable to a carbamino compound. A carbamino resonance that became prominent at higher pH was found at 28.4 ppm, and is tentatively ascribed to one or more adducts on epsilon amino groups. The beta chain resonances in particular are minimized by the presence of inositol hexaphosphate or 2,3-diphosphoglycerate. Quantitative analysis of the resonance intensities shows that the effects of conversion from the deoxy to the liganded state in reducing the degree of carbamino adduct is much more pronounced for the beta than for the alpha chains.", "contents": "Carbon 13 resonances of 13CO2 carbamino adducts of alpha and beta chains in human adult hemoglobin. The principal component of normal adult human hemoglobin Ao, was equilibrated under various conditions with 13CO2. In addition, derivatives containing specifically carbamylated NH2-terinal groups in alpha or beta chains, or both, were prepared by treatment with cyanate, and equilibrated likewise to allow the identification of specific resonances observed by 13C nuclear magnetic resonance. In deoxyhemoglobin, a resonanance at 29.2 ppm upfield of external CS2 was assigned to the alpha chain terminal adduct, and one at 29.8 ppm to the beta chain terminal adduct. In the liganded state as the CO derivative, the terminal adduct on both chains showed a common resonance position at 29.8 ppm. Small effects of pH on the resonance positions were observed. Under certain conditions, a resonance was observed at 33.4 ppm, probably not ascribable to a carbamino compound. A carbamino resonance that became prominent at higher pH was found at 28.4 ppm, and is tentatively ascribed to one or more adducts on epsilon amino groups. The beta chain resonances in particular are minimized by the presence of inositol hexaphosphate or 2,3-diphosphoglycerate. Quantitative analysis of the resonance intensities shows that the effects of conversion from the deoxy to the liganded state in reducing the degree of carbamino adduct is much more pronounced for the beta than for the alpha chains."}
{"id": "PMID:1396", "title": "Purine nucleotide cycle. Evidence for the occurrence of the cycle in brain.", "content": "Cell-free extracts of rat brain catalyze the reactions of the purine nucleotide cycle. Ammonia is formed during the deamination but not the amination phase of the cycle. The activity of adenylate deaminase in brain is sufficient to account for the maximum rates of ammonia production that have been reported. The activity of glutamate dehydrogenase is not sufficient to account for these rates of ammonia production. The activities of adenylosuccinate synthetase and adenylosuccinase are nearly sufficient to account for the steady state rates of ammonia production observed in brain. Demonstration of the cycle in extracts of brain is complicated by the occurrence of side reactions, in particular those catalyzed by phosphomonoesterase, nucleoside phosphorylase, and guanase.", "contents": "Purine nucleotide cycle. Evidence for the occurrence of the cycle in brain. Cell-free extracts of rat brain catalyze the reactions of the purine nucleotide cycle. Ammonia is formed during the deamination but not the amination phase of the cycle. The activity of adenylate deaminase in brain is sufficient to account for the maximum rates of ammonia production that have been reported. The activity of glutamate dehydrogenase is not sufficient to account for these rates of ammonia production. The activities of adenylosuccinate synthetase and adenylosuccinase are nearly sufficient to account for the steady state rates of ammonia production observed in brain. Demonstration of the cycle in extracts of brain is complicated by the occurrence of side reactions, in particular those catalyzed by phosphomonoesterase, nucleoside phosphorylase, and guanase."}
{"id": "PMID:1397", "title": "Kinetics of alpha-chymotrypsin dimerization.", "content": "A method has been devised which permits the observation of the loss of active sites promoted by aggregation of alpha-chymotrypsin. When alpha-chymotrypsin in unbuffered solution at pH 7 is mixed with buffered proflavin by stopped flow instrumentation to give a final pH of 3.89, a decrease in active sites occurs, as measured by a decrease in enzyme-dye complex. The decrease in the rate of active sites shows a linear dependence on the square of the concentration of active sites remaining at equilibrium. The kinetic data of the reaction have been correlated with equilibrium measurements. Rate constants for formation and dissociation of dimer are 9.45 X 10(3) M(-1)S(-1) and 1.9 S(-1),, respectively. Calculation of Kdis for dimer from rate constants gives a value of 2.01 X 10(-4) M, while direct determination of Kdis gives a value of 1.44 X 10(-4) M.", "contents": "Kinetics of alpha-chymotrypsin dimerization. A method has been devised which permits the observation of the loss of active sites promoted by aggregation of alpha-chymotrypsin. When alpha-chymotrypsin in unbuffered solution at pH 7 is mixed with buffered proflavin by stopped flow instrumentation to give a final pH of 3.89, a decrease in active sites occurs, as measured by a decrease in enzyme-dye complex. The decrease in the rate of active sites shows a linear dependence on the square of the concentration of active sites remaining at equilibrium. The kinetic data of the reaction have been correlated with equilibrium measurements. Rate constants for formation and dissociation of dimer are 9.45 X 10(3) M(-1)S(-1) and 1.9 S(-1),, respectively. Calculation of Kdis for dimer from rate constants gives a value of 2.01 X 10(-4) M, while direct determination of Kdis gives a value of 1.44 X 10(-4) M."}
{"id": "PMID:1399", "title": "Serum stimulation of phosphate uptake into 3T3 cells.", "content": "The stimulation by calf serum of phosphate uptake into 3T3 cells results from a change in maximum velocity of the transport process with no change in the Michaelis constant. Only arsenate among a series of inorganic structural analogs of phosphate inhibited phosphate uptake indicating a high specificity for the process. The arsenate inhibition was competitive in nature. Papaverine, theophylline, and protaglandin E1, drugs known to maintain high intracellular levels of cAMP, had little effect on serum stimulated phosphate uptake. The phosphate uptake stimulating factor(s) in serum could be distinguised from the 3T3 cell survival and migration factors by stability characteristics, but this factor(s) could not be completely separated from a uridine uptake stimulation activity or growth promoting activity using a variety of serum fractionation procedures. Only partial stimulation of the uptake process was achieved with any one serum fraction indicating a multiplicity of serum components is probably involved in this process. Because of the rapidity of serum activation of phosphate uptake and its apparent independence of intracellular cyclic nucleotide levels, it is suggested that serum factors may stimulate phosphate uptake by inducing structural changes in the phosphate carrier system.", "contents": "Serum stimulation of phosphate uptake into 3T3 cells. The stimulation by calf serum of phosphate uptake into 3T3 cells results from a change in maximum velocity of the transport process with no change in the Michaelis constant. Only arsenate among a series of inorganic structural analogs of phosphate inhibited phosphate uptake indicating a high specificity for the process. The arsenate inhibition was competitive in nature. Papaverine, theophylline, and protaglandin E1, drugs known to maintain high intracellular levels of cAMP, had little effect on serum stimulated phosphate uptake. The phosphate uptake stimulating factor(s) in serum could be distinguised from the 3T3 cell survival and migration factors by stability characteristics, but this factor(s) could not be completely separated from a uridine uptake stimulation activity or growth promoting activity using a variety of serum fractionation procedures. Only partial stimulation of the uptake process was achieved with any one serum fraction indicating a multiplicity of serum components is probably involved in this process. Because of the rapidity of serum activation of phosphate uptake and its apparent independence of intracellular cyclic nucleotide levels, it is suggested that serum factors may stimulate phosphate uptake by inducing structural changes in the phosphate carrier system."}
{"id": "PMID:1400", "title": "Dinoflagellate bioluminescence: a comparative study of invitro components.", "content": "In vitro bioluminescence components of the dinoflagellates Gonyaulax polyedra, G. tamarensis, Dissodinium lunual, and Pyrocystis noctiluca were studied. The luciferases and luciferins of the four species cross-react in all combinations. All of these species possess high-molecular weight luciferases (200,000-400,000 daltons) with similar pH activity profiles. The active single chains of luciferases from the Gonyaulax species have a MW of 130,000 while those from P. noctiluca and D. lunula have a MW of 60,000. Extractable luciferase activity varies with time of day in the two Gonyaulax species, but not in the other two. A luciferin binding protein (LBP) can easily be extracted from the two Gonyaulax species (MW approximately 120,000 daltons), but none could be detected in extracts of either D. lunula or P. noctiluca. Scintillons are extractable from all four species, but they vary in density and the degree to which activity can be increased by added luciferin. Although the biochemistry of bioluminescence in these dinoflagellates is generally similar, the observations that D. lunula and P. noctiluca apparently lack LBP and have luciferases with low MW single chains require further clarification.", "contents": "Dinoflagellate bioluminescence: a comparative study of invitro components. In vitro bioluminescence components of the dinoflagellates Gonyaulax polyedra, G. tamarensis, Dissodinium lunual, and Pyrocystis noctiluca were studied. The luciferases and luciferins of the four species cross-react in all combinations. All of these species possess high-molecular weight luciferases (200,000-400,000 daltons) with similar pH activity profiles. The active single chains of luciferases from the Gonyaulax species have a MW of 130,000 while those from P. noctiluca and D. lunula have a MW of 60,000. Extractable luciferase activity varies with time of day in the two Gonyaulax species, but not in the other two. A luciferin binding protein (LBP) can easily be extracted from the two Gonyaulax species (MW approximately 120,000 daltons), but none could be detected in extracts of either D. lunula or P. noctiluca. Scintillons are extractable from all four species, but they vary in density and the degree to which activity can be increased by added luciferin. Although the biochemistry of bioluminescence in these dinoflagellates is generally similar, the observations that D. lunula and P. noctiluca apparently lack LBP and have luciferases with low MW single chains require further clarification."}
{"id": "PMID:1401", "title": "Control of phenylalanine hydroxylase synthesis in tissue culture by serum and insulin.", "content": "Stationary-phase, minimal deviation hepatoma H4-II-E-C3 cell cultures that are serum-deprived respond with a biphasic time course of phenylalanine hydroxylase induction when dialyzed fetal calf serum or insulin is added. These two agents induce phenylalanine hydroxylase additively, during both the initial 3-hour and the delayed 24-hour phases. The initial phase of induction by insulin is inhibited by cycloheximide but not by actinomycin D. The delayed induction by both dialyzed fetal calf serum and insulin is inhibited by 10(-6) M cycloheximide and 0.20 mug/ml actinomycin D. H4-II-E-C3 cells in culture do not synthesize the factor(s) in serum that induce phenylalanine hydroxylase.", "contents": "Control of phenylalanine hydroxylase synthesis in tissue culture by serum and insulin. Stationary-phase, minimal deviation hepatoma H4-II-E-C3 cell cultures that are serum-deprived respond with a biphasic time course of phenylalanine hydroxylase induction when dialyzed fetal calf serum or insulin is added. These two agents induce phenylalanine hydroxylase additively, during both the initial 3-hour and the delayed 24-hour phases. The initial phase of induction by insulin is inhibited by cycloheximide but not by actinomycin D. The delayed induction by both dialyzed fetal calf serum and insulin is inhibited by 10(-6) M cycloheximide and 0.20 mug/ml actinomycin D. H4-II-E-C3 cells in culture do not synthesize the factor(s) in serum that induce phenylalanine hydroxylase."}
{"id": "PMID:1398", "title": "Effect of lumbar sympathetic blockade and chlorpromazine-induced adrenergic alpha-receptor blockade on skin temperature in peripheral arterial diseases.", "content": "The post-cooling toe temperature changes after lumbar sympathetic blockade and after intramuscular administration of an adrenergic alpha-receptor blocking substance (chlorpromazine) were studied in 14 patients with impending gangrene because of peripheral arterial insufficiency. The post-cooling temperature rise was similar after sympathetic blockage and chlorpromazine administration and significantly different from the basal toe temperature changes after cooling. It is concluded that administration of an adrenergic alpha-receptor blocking substance is as good as the lumbar sympathetic blockage for evaluation of a remaining sympathetic vasomotor tone in arterial disease patients.", "contents": "Effect of lumbar sympathetic blockade and chlorpromazine-induced adrenergic alpha-receptor blockade on skin temperature in peripheral arterial diseases. The post-cooling toe temperature changes after lumbar sympathetic blockade and after intramuscular administration of an adrenergic alpha-receptor blocking substance (chlorpromazine) were studied in 14 patients with impending gangrene because of peripheral arterial insufficiency. The post-cooling temperature rise was similar after sympathetic blockage and chlorpromazine administration and significantly different from the basal toe temperature changes after cooling. It is concluded that administration of an adrenergic alpha-receptor blocking substance is as good as the lumbar sympathetic blockage for evaluation of a remaining sympathetic vasomotor tone in arterial disease patients."}
{"id": "PMID:1405", "title": "High-speed ion-pair partition chromatography in pharmaceutical analysis.", "content": "Ion-pair chromatography offers attractive possibilities in pharmaceutical analysis. The specificity of the separation systems can be varied over a wide range by appropriate selection of the stationary phase. The choice of a suitable counter-ion can also drastically improve the detection limit, permitting the determination of drug substances in low dosage and possibly of by-products or breakdown products. Ion-pair chromatography of tropane and ergot alkaloids has been investigated using picrate as counter-ion. Alumina, Kieselguhr and various grades of silica gel have been tested as supports. Partition properties studied in a batch procedure have been compared with the actual chromatographic conditions. Columns (10 cm) filled with silical gel (particle size, 5 mum; pore size, 1000 A) show the best performance in the separation of hyoscyamine, scopolamine and ergotamine as picrate ion-pairs. Close control of pH and temperature is essential for reproducible separations. Improvements in detection limits between 100 and 300 times have been observed with these systems. Ion-pair extractions of these alkaloids from dosage forms can be used for sample preparation prior to injection on the the column. This provides an added degree of selectivity and sensitivity.", "contents": "High-speed ion-pair partition chromatography in pharmaceutical analysis. Ion-pair chromatography offers attractive possibilities in pharmaceutical analysis. The specificity of the separation systems can be varied over a wide range by appropriate selection of the stationary phase. The choice of a suitable counter-ion can also drastically improve the detection limit, permitting the determination of drug substances in low dosage and possibly of by-products or breakdown products. Ion-pair chromatography of tropane and ergot alkaloids has been investigated using picrate as counter-ion. Alumina, Kieselguhr and various grades of silica gel have been tested as supports. Partition properties studied in a batch procedure have been compared with the actual chromatographic conditions. Columns (10 cm) filled with silical gel (particle size, 5 mum; pore size, 1000 A) show the best performance in the separation of hyoscyamine, scopolamine and ergotamine as picrate ion-pairs. Close control of pH and temperature is essential for reproducible separations. Improvements in detection limits between 100 and 300 times have been observed with these systems. Ion-pair extractions of these alkaloids from dosage forms can be used for sample preparation prior to injection on the the column. This provides an added degree of selectivity and sensitivity."}
{"id": "PMID:1406", "title": "Analytical separation of amino acids on a cation-exchange resin cross-linked with m-divinylbenzene.", "content": "The elution bands of acidic and neutral amino acids of protein hydrolysates, emerging from the column of a cation-exchange resin cross-linked with pure m-divinylbenzene, are narrower than those from a resin prepared from styrene and technical divinylbenzene. As a result of these narrower bands, a more complete resolution of the critical pairs threonine-serine, glycine-alanine and tyrosine-phenylalanine is obtained. The most probable reason for the narrower elution peaks is the more rapid diffusion of the exchanged components through the bulk of the resin as a result of a more regular arrangement of cross-linkages in the cation-exchange resin prepared from m-divinylbenzene.", "contents": "Analytical separation of amino acids on a cation-exchange resin cross-linked with m-divinylbenzene. The elution bands of acidic and neutral amino acids of protein hydrolysates, emerging from the column of a cation-exchange resin cross-linked with pure m-divinylbenzene, are narrower than those from a resin prepared from styrene and technical divinylbenzene. As a result of these narrower bands, a more complete resolution of the critical pairs threonine-serine, glycine-alanine and tyrosine-phenylalanine is obtained. The most probable reason for the narrower elution peaks is the more rapid diffusion of the exchanged components through the bulk of the resin as a result of a more regular arrangement of cross-linkages in the cation-exchange resin prepared from m-divinylbenzene."}
{"id": "PMID:1407", "title": "[Template chromatography on immobilized oligonucleotides. Synthesis and application of oligodeoxyadenosine-5'-phosphate--DEAE-cellulose (author's transl)].", "content": "Oligomers of deoxyadenylic acid, obtained by polycondensation, were covalently attached to polyvinyl alcohol. These polymer-bound oligonucleotides undergo very strong adsorption on DEAE-cellulose such that at neutral pH and with 1 M NaCl, partial desorbtion occurs only above 60 degrees. The use of this PV(pA)n-DEAE-cellulose for the column chromatographic separation of deoxythymidylic acid oligomers obtained by polycondensation, according to the principle of base-pairing, is discussed. Linear oligomers and also pyrophosphate derivatives of thymidylic acid which contain more than five monomer units undergo strong retardation under the conditions of base-pairing. Cyclic oligonucleotides do not show any noticeable interaction with the stationary phase. Thus, through the use of a temperature gradient, it is possible to fractionally separate the polycondensate, giving an average degree of polymerisation of 6--10.", "contents": "[Template chromatography on immobilized oligonucleotides. Synthesis and application of oligodeoxyadenosine-5'-phosphate--DEAE-cellulose (author's transl)]. Oligomers of deoxyadenylic acid, obtained by polycondensation, were covalently attached to polyvinyl alcohol. These polymer-bound oligonucleotides undergo very strong adsorption on DEAE-cellulose such that at neutral pH and with 1 M NaCl, partial desorbtion occurs only above 60 degrees. The use of this PV(pA)n-DEAE-cellulose for the column chromatographic separation of deoxythymidylic acid oligomers obtained by polycondensation, according to the principle of base-pairing, is discussed. Linear oligomers and also pyrophosphate derivatives of thymidylic acid which contain more than five monomer units undergo strong retardation under the conditions of base-pairing. Cyclic oligonucleotides do not show any noticeable interaction with the stationary phase. Thus, through the use of a temperature gradient, it is possible to fractionally separate the polycondensate, giving an average degree of polymerisation of 6--10."}
{"id": "PMID:1408", "title": "A rapid and comprehensive system for the routine identification of drugs in biological material based on microphase extraction and drug colour profiles.", "content": "The separation of basic, acidic and neutral drugs from propanol-2 extracts of serum, urine and tissue homogenates at different pH values using a micro-phase extraction technique is described. Following preliminary screening, the various drug-containing fractions obtained are further examined by two-dimensional thin-layer chromatography. The drugs present are identified with reference to documented standards with the aid of a drug colour profile system and RF values relative to three different reference standards. By means of gas chromatographic analysis of the same extracts, semi-quantitative estimates of the amounts of drugs present, which are sufficiently accurate for clinical emergency purposes, can be made in many instances. The main advantages of the system are \"clean\" extracts with a minimum of background interference, rapidity (4-6 h for a complete analysis) and systematically documented and visually presented behaviour of drugs after spraying with various chromogenic and fluorogenic reagents, allowing the systematic identification of unknown substances.", "contents": "A rapid and comprehensive system for the routine identification of drugs in biological material based on microphase extraction and drug colour profiles. The separation of basic, acidic and neutral drugs from propanol-2 extracts of serum, urine and tissue homogenates at different pH values using a micro-phase extraction technique is described. Following preliminary screening, the various drug-containing fractions obtained are further examined by two-dimensional thin-layer chromatography. The drugs present are identified with reference to documented standards with the aid of a drug colour profile system and RF values relative to three different reference standards. By means of gas chromatographic analysis of the same extracts, semi-quantitative estimates of the amounts of drugs present, which are sufficiently accurate for clinical emergency purposes, can be made in many instances. The main advantages of the system are \"clean\" extracts with a minimum of background interference, rapidity (4-6 h for a complete analysis) and systematically documented and visually presented behaviour of drugs after spraying with various chromogenic and fluorogenic reagents, allowing the systematic identification of unknown substances."}
{"id": "PMID:1410", "title": "Chromatographic behaviour of alkaloids on thin layers of anion and cation exhangers. I. AG 1-X4 and cellex D.", "content": "The chromatographic behaviour of 48 alkaloids has been studied on Bio-Rad AG 1-X4, Cellex D and microcrystalline cellulose, eluting with solutions of different pH but constant ionic strength (0.5). Many interesting separations were effected on both AG 1-X4 and Cellex D layers. The influence of pH on the chromatographic behaviour of alkaloids has been quantitatively studied and an equation was used that expresses the behaviour of the alkaloids on both AG 1-X4 (AcO-) and microcrystalling cellulose layers. The nonapplicability of this equation to Cellex D layers is discussed.", "contents": "Chromatographic behaviour of alkaloids on thin layers of anion and cation exhangers. I. AG 1-X4 and cellex D. The chromatographic behaviour of 48 alkaloids has been studied on Bio-Rad AG 1-X4, Cellex D and microcrystalline cellulose, eluting with solutions of different pH but constant ionic strength (0.5). Many interesting separations were effected on both AG 1-X4 and Cellex D layers. The influence of pH on the chromatographic behaviour of alkaloids has been quantitatively studied and an equation was used that expresses the behaviour of the alkaloids on both AG 1-X4 (AcO-) and microcrystalling cellulose layers. The nonapplicability of this equation to Cellex D layers is discussed."}
{"id": "PMID:1411", "title": "Determination of trimethylsilyl methylated nucleic acid bases in urine by gas-liquid chromatography.", "content": "A method for the determination of the urinary excretion level of methylated nucleic acid bases by gas-liquid chromatography (GLC) has been developed. A clean-up procedure prior to GLC analysis consisted of hydrolysis, filtration, charcoal adsorption, and anion exchange. Studies to determine optimum derivatization conditions for conversion of the methylated bases to their trimethylsilyl derivatives and to evaluate GLC parameters and columns to obtain the best separation were conducted. Application of the method was shown by determining the excretion levels of methylated bases in urine of normal controls and of patients with various types of malignancy.", "contents": "Determination of trimethylsilyl methylated nucleic acid bases in urine by gas-liquid chromatography. A method for the determination of the urinary excretion level of methylated nucleic acid bases by gas-liquid chromatography (GLC) has been developed. A clean-up procedure prior to GLC analysis consisted of hydrolysis, filtration, charcoal adsorption, and anion exchange. Studies to determine optimum derivatization conditions for conversion of the methylated bases to their trimethylsilyl derivatives and to evaluate GLC parameters and columns to obtain the best separation were conducted. Application of the method was shown by determining the excretion levels of methylated bases in urine of normal controls and of patients with various types of malignancy."}
{"id": "PMID:1412", "title": "High-resolution liquid chromatographic analysis of methylated purine and pyrimidine bases in transfer RNA.", "content": "Methylated and major purine and pyrimidine bases were separated and quantified by high-resolution liquid chromatography after hydrolyzing transfer ribonucleic acids (tRNAs). Separation was accomplished by eluting the hydrolyzed samples from an anion-exchange column with a concentration gradient of ammonium acetate at pH 9.2. Isolated sample of tRNA were hydrolyzed to the free bases with a trifluoroacetic acid-formic acid mixture of 200 degrees. Detection limits of 100-200 ng/ml were measured for the methylated bases; analytical data are reported for ten methylated bases plus the four major bases of calf liver and rat liver tRNA.", "contents": "High-resolution liquid chromatographic analysis of methylated purine and pyrimidine bases in transfer RNA. Methylated and major purine and pyrimidine bases were separated and quantified by high-resolution liquid chromatography after hydrolyzing transfer ribonucleic acids (tRNAs). Separation was accomplished by eluting the hydrolyzed samples from an anion-exchange column with a concentration gradient of ammonium acetate at pH 9.2. Isolated sample of tRNA were hydrolyzed to the free bases with a trifluoroacetic acid-formic acid mixture of 200 degrees. Detection limits of 100-200 ng/ml were measured for the methylated bases; analytical data are reported for ten methylated bases plus the four major bases of calf liver and rat liver tRNA."}
{"id": "PMID:1414", "title": "A new gas chromatographic method for the estimation of reserpine and rescinnamine.", "content": "Under the conditions described for alkaline hydrolysis of reserpine and rescinnamine in absolute and aqueous methanol, and after esterification (with diazomethane) of the resulting acid fraction, methyl 3,4,5-trimethoxybenzoate was quantitatively recovered, whereas methyl trans-3,4,5-trimethoxycinnamate, in normal lighting conditions, was either partly isomerized to methyl cis-trimethoxycinnamate or formed an adduct with a molecule of methanol, yielding methyl 3-methoxy-3-(3,4,5-trimethoxyphenyl)propionate. The structures of the products were established by synthesis, nuclear magnetic resonance studies and mass spectrometry. This investigation of the hydrolytic conditions allowed a reliable and rapid gas chromatographic determination of reserpine and/or rescinnamine in amounts down to 500 and 2000 mug, respectively, to be devised.", "contents": "A new gas chromatographic method for the estimation of reserpine and rescinnamine. Under the conditions described for alkaline hydrolysis of reserpine and rescinnamine in absolute and aqueous methanol, and after esterification (with diazomethane) of the resulting acid fraction, methyl 3,4,5-trimethoxybenzoate was quantitatively recovered, whereas methyl trans-3,4,5-trimethoxycinnamate, in normal lighting conditions, was either partly isomerized to methyl cis-trimethoxycinnamate or formed an adduct with a molecule of methanol, yielding methyl 3-methoxy-3-(3,4,5-trimethoxyphenyl)propionate. The structures of the products were established by synthesis, nuclear magnetic resonance studies and mass spectrometry. This investigation of the hydrolytic conditions allowed a reliable and rapid gas chromatographic determination of reserpine and/or rescinnamine in amounts down to 500 and 2000 mug, respectively, to be devised."}
{"id": "PMID:1415", "title": "Specific ion-exchange chromatography and fluorimetric assay for urinary 3-O-methyldopamine.", "content": "A technique for the selective extraction of 3-O-methyldopamine, normetanephrine and metanephrine from a single urine sample has been investigated. After hydrolysis of the conjugates, the diluted mixture is passed through a Dowex 50W-X2 column and the methoxylated amines are eluted by means of concentrated ammonia. The eluate, containing metanephrine, normetanephrine and 3-O-methyldopamine is evaporated, and a solution of the residue in borate buffer is fractionated under strictly controlled conditions on an Amberlite CG-50 column. The three amines so separated are estimated by specific fluorimetric methods. The extraction recovery is 80 +/- 3% for pure solutions and 78 +/- 4% for 3-O-methyldopamine added to urine. The fluorimetric procedure, carried out under well-defined conditions, allows the estimation of 10 ng of 3-O-methethyldopamine. The spectral characteristics of the fluorescent derivative are similar to those obtained with dopamine, so that it can be assumed that iodine oxidation of 3-O-methyldopamine demethylates this compound and oxidises the resulting dopamine to the dopamine fluorophore (5,6-dihydroxy-indole). Of the compounds that might interfere in the fluorimetric procedure, dopamine, DOPA and alpha-methyl-DOPA are destroyed by the ammoniacal elution from the Dowex column and 3-O-methyl-DOPA is eliminated in the effluent from the Amberlite column. The elimination of interfering compounds and the improved separation on Amberlite ensure high specificity for this procedure. We have applied the method to normal urine and to pathological urines from patients with adrenergic tumours or untreated and treated parkinsonian subjects; vital information has been obtained on the prognosis of adrenergic tumours. The presence of large amounts of dopamine, normetanephrine and/or metanephrine does not affect the assay for 3-O-methyldopamine. The method is also applicable to rat and dog urine, and can be applied to tissue extracts with little modification.", "contents": "Specific ion-exchange chromatography and fluorimetric assay for urinary 3-O-methyldopamine. A technique for the selective extraction of 3-O-methyldopamine, normetanephrine and metanephrine from a single urine sample has been investigated. After hydrolysis of the conjugates, the diluted mixture is passed through a Dowex 50W-X2 column and the methoxylated amines are eluted by means of concentrated ammonia. The eluate, containing metanephrine, normetanephrine and 3-O-methyldopamine is evaporated, and a solution of the residue in borate buffer is fractionated under strictly controlled conditions on an Amberlite CG-50 column. The three amines so separated are estimated by specific fluorimetric methods. The extraction recovery is 80 +/- 3% for pure solutions and 78 +/- 4% for 3-O-methyldopamine added to urine. The fluorimetric procedure, carried out under well-defined conditions, allows the estimation of 10 ng of 3-O-methethyldopamine. The spectral characteristics of the fluorescent derivative are similar to those obtained with dopamine, so that it can be assumed that iodine oxidation of 3-O-methyldopamine demethylates this compound and oxidises the resulting dopamine to the dopamine fluorophore (5,6-dihydroxy-indole). Of the compounds that might interfere in the fluorimetric procedure, dopamine, DOPA and alpha-methyl-DOPA are destroyed by the ammoniacal elution from the Dowex column and 3-O-methyl-DOPA is eliminated in the effluent from the Amberlite column. The elimination of interfering compounds and the improved separation on Amberlite ensure high specificity for this procedure. We have applied the method to normal urine and to pathological urines from patients with adrenergic tumours or untreated and treated parkinsonian subjects; vital information has been obtained on the prognosis of adrenergic tumours. The presence of large amounts of dopamine, normetanephrine and/or metanephrine does not affect the assay for 3-O-methyldopamine. The method is also applicable to rat and dog urine, and can be applied to tissue extracts with little modification."}
{"id": "PMID:1416", "title": "Analysis of the radioimmunoassay for gonadotropin-releasing hormone (GnRH): studies on the effect of radioiodinated GnRH.", "content": "When GnRH is radioiodinated by the chloramine-T method, two immunoreactive labeled species are formed at pH 6.5 with a chloramine-T: GnRH molar ratio of 11:1, whereas four bands (I, IIa, IIb, and III) are separated by polyacrylamide gel electrophoresis when the hormone is iodinated at pH 7.5 in a system containing a 97:1 molar ratio of chloramine-T:GnRH. Because they were more stable and were more immunoreactive than the other products, band I and band IIa from the latter system were used separately as tracers with Niswender antiserum R-42 in radioimmunoassays for GnRH. The standard curves of each tracer are distinct: when analyzed after log-logit transformation, the band I curve had a mean slope of -3.31 +/- 0.2 (SE) and a 50% B/Bt level of 9 +/- 0.8 pg (n=8) of synthetic GnRH, whereas the band IIa standard curve had a slope of -2.30 +/- 0.6 and a 50% B/Bt value of 20 +/- 0.9 pg (n=11). The sensitivity of both assays is approximately 2.0 pg. Gn RH concentrations in plasma and serum samples assayed with band I were consistently greater than those assayed with band IIa. Normal adult male plasmas assayed with band I measured 21 +/- 0.9 pg/ml, whereas band IIa values were 8 +/- 0.4 pg/ml. No difference between plasma and serum was detected, nor was there any difference among adult men, adult women, prepubertal children, hypogonadal patients, or hypopituitary patients with either assay. Plasma GnRH concentrations were also similar in jugular and vena cava samples from intact and castrated male rats. Because many of the samples were at or below the sensitivity of the band IIa assay, they were concentrated after extraction with either methanol or acid-ethanol. However, endogenous immunoreactive GnRH could not be concentrated by these extraction procedures. As measured in the band IIa assay, hypothalamic extracts from control adult male rats contained 3.1 +/- 0.4 ng while hypothalami from castrated rats contained 1.4 +/- 0.1 ng. Similar but slightly lower values were obtained with band I. In contrast, the GnRH content of pineal glands from intact and castrated male rats was similar (approximately 150 pg) when determined in either assay. These studies emphasize that: 1) the characteristics of the radioiodinated hormone can influence the quantitation of GnRH; and 2) endogenous plasma concentrations of GnRH are much lower than previously reported.", "contents": "Analysis of the radioimmunoassay for gonadotropin-releasing hormone (GnRH): studies on the effect of radioiodinated GnRH. When GnRH is radioiodinated by the chloramine-T method, two immunoreactive labeled species are formed at pH 6.5 with a chloramine-T: GnRH molar ratio of 11:1, whereas four bands (I, IIa, IIb, and III) are separated by polyacrylamide gel electrophoresis when the hormone is iodinated at pH 7.5 in a system containing a 97:1 molar ratio of chloramine-T:GnRH. Because they were more stable and were more immunoreactive than the other products, band I and band IIa from the latter system were used separately as tracers with Niswender antiserum R-42 in radioimmunoassays for GnRH. The standard curves of each tracer are distinct: when analyzed after log-logit transformation, the band I curve had a mean slope of -3.31 +/- 0.2 (SE) and a 50% B/Bt level of 9 +/- 0.8 pg (n=8) of synthetic GnRH, whereas the band IIa standard curve had a slope of -2.30 +/- 0.6 and a 50% B/Bt value of 20 +/- 0.9 pg (n=11). The sensitivity of both assays is approximately 2.0 pg. Gn RH concentrations in plasma and serum samples assayed with band I were consistently greater than those assayed with band IIa. Normal adult male plasmas assayed with band I measured 21 +/- 0.9 pg/ml, whereas band IIa values were 8 +/- 0.4 pg/ml. No difference between plasma and serum was detected, nor was there any difference among adult men, adult women, prepubertal children, hypogonadal patients, or hypopituitary patients with either assay. Plasma GnRH concentrations were also similar in jugular and vena cava samples from intact and castrated male rats. Because many of the samples were at or below the sensitivity of the band IIa assay, they were concentrated after extraction with either methanol or acid-ethanol. However, endogenous immunoreactive GnRH could not be concentrated by these extraction procedures. As measured in the band IIa assay, hypothalamic extracts from control adult male rats contained 3.1 +/- 0.4 ng while hypothalami from castrated rats contained 1.4 +/- 0.1 ng. Similar but slightly lower values were obtained with band I. In contrast, the GnRH content of pineal glands from intact and castrated male rats was similar (approximately 150 pg) when determined in either assay. These studies emphasize that: 1) the characteristics of the radioiodinated hormone can influence the quantitation of GnRH; and 2) endogenous plasma concentrations of GnRH are much lower than previously reported."}
{"id": "PMID:1417", "title": "Counterimmunoelectrophoresis of pneumococcal antigens:improved sensitivity for the detection of types VII and XIV.", "content": "Rapid identification of Streptococcus pneumoniae has been reported using counterimmunoelectrophoresis for the detection of specific capsular antigens in serum, cerebrospinal fluid, and urine. Previous clinical studies have failed to detect type VII or XIV pneumococcal antigen. These two types, however, account for a significant portion of pneumococcal disease. The incorporation of a sulfonated derivative of phenylboronic acid in the buffer system provides a method for the sensitive detection of these types in artificial mixtures without greatly reducing the sensitivity for the detection of other pneumococcal types. A problem with false positives encountered using human serum and barbitalbuffer was reduced by the use of buffer containing sulfonated phenylboronic acid.", "contents": "Counterimmunoelectrophoresis of pneumococcal antigens:improved sensitivity for the detection of types VII and XIV. Rapid identification of Streptococcus pneumoniae has been reported using counterimmunoelectrophoresis for the detection of specific capsular antigens in serum, cerebrospinal fluid, and urine. Previous clinical studies have failed to detect type VII or XIV pneumococcal antigen. These two types, however, account for a significant portion of pneumococcal disease. The incorporation of a sulfonated derivative of phenylboronic acid in the buffer system provides a method for the sensitive detection of these types in artificial mixtures without greatly reducing the sensitivity for the detection of other pneumococcal types. A problem with false positives encountered using human serum and barbitalbuffer was reduced by the use of buffer containing sulfonated phenylboronic acid."}
{"id": "PMID:1418", "title": "Isolation of streptococcal nuclease B by batch adsorption.", "content": "A method has been developed for the preparation of streptococcal nuclease B by batch adsorpton to diethylaminoethyl-cellulose. The enzyme is homogeneous with respect to nuclease activity and is suitable for use as an antigen in measurement of anti-deoxyribonuclease B levels in sera.", "contents": "Isolation of streptococcal nuclease B by batch adsorption. A method has been developed for the preparation of streptococcal nuclease B by batch adsorpton to diethylaminoethyl-cellulose. The enzyme is homogeneous with respect to nuclease activity and is suitable for use as an antigen in measurement of anti-deoxyribonuclease B levels in sera."}
{"id": "PMID:1419", "title": "Rapid screening of Veillonella by ultraviolet fluorescence.", "content": "Among 51 strains of anaerobic gram-negative cocci belonging to the family Veillonellaceae, all strains of Veillonella (V. parvula and V. alcalescens) displayed red fluorescence under long-wave (366 nm) ultraviolet light, whereas no Acidaminococcus or Megasphaera demonstrated fluorescence. In contrast to Bacteroides melaninogenicus, growth of Veillonella does not require hemin and menadione, and flourescence is rapidly lost upon exposure to air. The fluorescent component of a strain of V. parvula examined could not be extracted in solution with water, ether, methanol, or chloroform, but was readily extracted with 0.4 N NaOH. Spectrophotofluorometrically, the fluorescence maximum of this extract was 660 nm with an excitation maximum of 300 nm, when measured at pH 7.2 and 25 C. Coupled with the Gram stain, ultraviolet fluorescence may be a  useful tool for rapid screening of Veillonella and is particularly helpful for detection and, isolation of this organism from mixed culture.", "contents": "Rapid screening of Veillonella by ultraviolet fluorescence. Among 51 strains of anaerobic gram-negative cocci belonging to the family Veillonellaceae, all strains of Veillonella (V. parvula and V. alcalescens) displayed red fluorescence under long-wave (366 nm) ultraviolet light, whereas no Acidaminococcus or Megasphaera demonstrated fluorescence. In contrast to Bacteroides melaninogenicus, growth of Veillonella does not require hemin and menadione, and flourescence is rapidly lost upon exposure to air. The fluorescent component of a strain of V. parvula examined could not be extracted in solution with water, ether, methanol, or chloroform, but was readily extracted with 0.4 N NaOH. Spectrophotofluorometrically, the fluorescence maximum of this extract was 660 nm with an excitation maximum of 300 nm, when measured at pH 7.2 and 25 C. Coupled with the Gram stain, ultraviolet fluorescence may be a  useful tool for rapid screening of Veillonella and is particularly helpful for detection and, isolation of this organism from mixed culture."}
{"id": "PMID:1420", "title": "Retention of mercurial preservatives in desiccated biological products.", "content": "A variety of bacterins, vaccines, and antisera retained greater than 90% of their original level of mercurial preservative after lyophilization, and this might influence certain uses of these products.", "contents": "Retention of mercurial preservatives in desiccated biological products. A variety of bacterins, vaccines, and antisera retained greater than 90% of their original level of mercurial preservative after lyophilization, and this might influence certain uses of these products."}
{"id": "PMID:1421", "title": "Distribution and removal of added mercury in milk.", "content": "Distribution patterns of added mercury in raw whole milk after equilibration for 30 min and 2 h at 37 C showed a distribution among acid casein, whey proteins, fat globule membrane, and soluble fat globule membrane of 33, 28, 16, and 2%. On the basis of protein content, the fat globule membrane had the highest amount of mercury. Mercury added to milk as mercuric chloride was removed by treatment with thiolated aminoethyl celluloses and reduced human hair. In a 5 min treatment, 70, 43, and 41% of the mercury was removed by thiosuccinylated aminoethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced human hair, respectively, from whole milk initially containing 1 ppm mercury and equilibrated for 2 h at 37 C prior to treatment. After treatment for 60 min, 82, 52, and 64% of the mercury was removed by thiosuccinilated aminoethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced hair, respectively. However, increasing incubation temperature and time prior to treatment decreased the removal efficiencies. Thiosuccinilated aminoethyl cellulose and reduced human hair showed increasing efficiency directly with pH, while thionitrocarboxyphenylated aminoethyl cellulose showed the opposite effect and had higher affinity for mercury at pH 5.5 than at pH 7.5. Moreover, the rate of removal of mercury at 4 C compared to 37 C was much slower. The removal of mercury from soluble casein and soluble whey proteins was more efficient than from micellar casein. Protein, lactose content, and pH of milk were not changed by the polymer treatments.", "contents": "Distribution and removal of added mercury in milk. Distribution patterns of added mercury in raw whole milk after equilibration for 30 min and 2 h at 37 C showed a distribution among acid casein, whey proteins, fat globule membrane, and soluble fat globule membrane of 33, 28, 16, and 2%. On the basis of protein content, the fat globule membrane had the highest amount of mercury. Mercury added to milk as mercuric chloride was removed by treatment with thiolated aminoethyl celluloses and reduced human hair. In a 5 min treatment, 70, 43, and 41% of the mercury was removed by thiosuccinylated aminoethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced human hair, respectively, from whole milk initially containing 1 ppm mercury and equilibrated for 2 h at 37 C prior to treatment. After treatment for 60 min, 82, 52, and 64% of the mercury was removed by thiosuccinilated aminoethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced hair, respectively. However, increasing incubation temperature and time prior to treatment decreased the removal efficiencies. Thiosuccinilated aminoethyl cellulose and reduced human hair showed increasing efficiency directly with pH, while thionitrocarboxyphenylated aminoethyl cellulose showed the opposite effect and had higher affinity for mercury at pH 5.5 than at pH 7.5. Moreover, the rate of removal of mercury at 4 C compared to 37 C was much slower. The removal of mercury from soluble casein and soluble whey proteins was more efficient than from micellar casein. Protein, lactose content, and pH of milk were not changed by the polymer treatments."}
{"id": "PMID:1437", "title": "Demonstration of a nonadrenergic inhibitory nervous system in the trachea of the guinea pig.", "content": "A nonadrenergic inhibitory nervous system has been demonstrated in the guinea pig trachea. Electrical field stimulation of this system, in the presence of adrenergic and cholinergic blockade, resulted in relaxation of tracheal rings contracted by the mediators of immediate hypersensitivity or histamine. The relaxation was blocked by tetrodotoxin, which indicated that nerve stimulation was responsible for the relaxation. The gastrointestinal tract, which has a similar embryological origin to the respiratory tract, also has a nonadrenergic inhibitory system. In the gastrointestinal tract, this system is thought to be responsible for the relaxation phase of peristalsis, and absence of this system, in the colon and the rectum, is thought to be an explanation for the spastic bowel in Hirschsprung's disease. It is possible that an abnormality of the respiratory nonadrenergic inhibitory system may play a role in the pathogenesis of the hyperreactive airways in asthma. The airways, due to a lack of inhibition, may be either partially contracted or unable to relax, and thus appear hyperreactive to stimuli.", "contents": "Demonstration of a nonadrenergic inhibitory nervous system in the trachea of the guinea pig. A nonadrenergic inhibitory nervous system has been demonstrated in the guinea pig trachea. Electrical field stimulation of this system, in the presence of adrenergic and cholinergic blockade, resulted in relaxation of tracheal rings contracted by the mediators of immediate hypersensitivity or histamine. The relaxation was blocked by tetrodotoxin, which indicated that nerve stimulation was responsible for the relaxation. The gastrointestinal tract, which has a similar embryological origin to the respiratory tract, also has a nonadrenergic inhibitory system. In the gastrointestinal tract, this system is thought to be responsible for the relaxation phase of peristalsis, and absence of this system, in the colon and the rectum, is thought to be an explanation for the spastic bowel in Hirschsprung's disease. It is possible that an abnormality of the respiratory nonadrenergic inhibitory system may play a role in the pathogenesis of the hyperreactive airways in asthma. The airways, due to a lack of inhibition, may be either partially contracted or unable to relax, and thus appear hyperreactive to stimuli."}
{"id": "PMID:1442", "title": "Non-specific alkaline phosphomonoesterases of eight species of digenetic trematodes.", "content": "Alkaline phosphatases from different trematodes occupying the same habitat have identical pH otima but different levels of enzyme activities. Isoparorchis hypselobagri, from the fish Wallago attu, shows four to six times more enzyme activity than Fasciolopsis buski, Gastrodiscoides hominis and Echinostoma malayanum, from the pig Sus scrofa, and Fasciola gigantica, Gigantocotyle explanatum, Cotylophoron cotylophorum and Gastrothylax crumenifer, from the buffalo Bubalus bubalis. At least two peaks of activity at different levels of pH were obtained for each trematode examined. Both Gastrodiscoides hominis and Isoparorchis hypselobagri enzymes had three peaks of alkaline phosphatase activity. The optimum temperature for maximum enzyme activity was 40 degrees C, above which rapid inactivation occurred. At temperatures below 40 degrees C, the enzymes of fish and mammalian trematodes did not behave similarly; I. hypselobagri enzyme being active over a wider range of temperature (20 degrees-40 degrees C. Various concentrations of KCN and arsenate proportionately inhibited enzyme activity. NaF Did not significantly influence enzyme activity, while Mg++ and Co++ acted as activators. The extent of inhibition or activation of enzyme activity of different trematodes varied, probably due to species differences. Both inhibition and activation of I. hypselobagri enzyme was higher than in the case of other trematodes.", "contents": "Non-specific alkaline phosphomonoesterases of eight species of digenetic trematodes. Alkaline phosphatases from different trematodes occupying the same habitat have identical pH otima but different levels of enzyme activities. Isoparorchis hypselobagri, from the fish Wallago attu, shows four to six times more enzyme activity than Fasciolopsis buski, Gastrodiscoides hominis and Echinostoma malayanum, from the pig Sus scrofa, and Fasciola gigantica, Gigantocotyle explanatum, Cotylophoron cotylophorum and Gastrothylax crumenifer, from the buffalo Bubalus bubalis. At least two peaks of activity at different levels of pH were obtained for each trematode examined. Both Gastrodiscoides hominis and Isoparorchis hypselobagri enzymes had three peaks of alkaline phosphatase activity. The optimum temperature for maximum enzyme activity was 40 degrees C, above which rapid inactivation occurred. At temperatures below 40 degrees C, the enzymes of fish and mammalian trematodes did not behave similarly; I. hypselobagri enzyme being active over a wider range of temperature (20 degrees-40 degrees C. Various concentrations of KCN and arsenate proportionately inhibited enzyme activity. NaF Did not significantly influence enzyme activity, while Mg++ and Co++ acted as activators. The extent of inhibition or activation of enzyme activity of different trematodes varied, probably due to species differences. Both inhibition and activation of I. hypselobagri enzyme was higher than in the case of other trematodes."}
{"id": "PMID:1444", "title": "The effect of neonatal rat graft-vs-host disease (GVHD) on Fc receptor lymphocytes.", "content": "The level  of Fc receptor rosette-forming lymphocytes (Fc-RFL) was examined in spleen and lymph node cell suspension from neonatal DA and BN rats inoculated within 24 hr of birth with either allogeneic L (experimental) or syngeneic (control) lymphoid cells. In addition, these levels were compared to fetal and neonatal animals that received no injection. The indicator cells (EA) were sheep erythrocytes sensitized with one-half concentration of the highest dilution of rabbit anti-sheep erythrocyte IgG(A) which agglutinated an equal amount of 1% suspension of E. Care was taken to exclude scoring macrophages by injecting colloidal carbon at least 1 hr before killing the test animals. The spleen of 19-day DA fetal rats exhibited a level of 19.3% Fc-RFL, similar to that of animals having received adult syngeneic cells at birth (40.0%) by day 7. Thereafter the level of Fc-RFL did not vary appreciably between these two groups. However, as early as 2 days after inoculation there was a significantly greater number of Fc-RFL in the spleen of experimental DA neonates compared to controls. The lymph nodes of experimental animals did not exhibit a significantly greater number of Fc-RFL until day 6 with both tissue compartments peaking at day 10 and remaining significantly higher than controls until death. In neonatal BN animals significantly higher levels of Fc-RFL in experimental animals were not evident as early and peaked later (day 12) in both tissue compartments but again these differences remained until death. Cytotoxic alloantisera demonstrated that on days 6, 10, and 12 most, if not all, of the Fc-RFL were host in origion in both DA and BN GVHD, with a very significant host plasma cell response in such GVHD animals. One-micron tissue section revealed the presence of a great number of plasma cell especially prominent in the medulla of lymph nodes with the cortex of lymph nodes and white pulp of the spleen markedly depleted of lymphocytes indicative of cytotoxicity.", "contents": "The effect of neonatal rat graft-vs-host disease (GVHD) on Fc receptor lymphocytes. The level  of Fc receptor rosette-forming lymphocytes (Fc-RFL) was examined in spleen and lymph node cell suspension from neonatal DA and BN rats inoculated within 24 hr of birth with either allogeneic L (experimental) or syngeneic (control) lymphoid cells. In addition, these levels were compared to fetal and neonatal animals that received no injection. The indicator cells (EA) were sheep erythrocytes sensitized with one-half concentration of the highest dilution of rabbit anti-sheep erythrocyte IgG(A) which agglutinated an equal amount of 1% suspension of E. Care was taken to exclude scoring macrophages by injecting colloidal carbon at least 1 hr before killing the test animals. The spleen of 19-day DA fetal rats exhibited a level of 19.3% Fc-RFL, similar to that of animals having received adult syngeneic cells at birth (40.0%) by day 7. Thereafter the level of Fc-RFL did not vary appreciably between these two groups. However, as early as 2 days after inoculation there was a significantly greater number of Fc-RFL in the spleen of experimental DA neonates compared to controls. The lymph nodes of experimental animals did not exhibit a significantly greater number of Fc-RFL until day 6 with both tissue compartments peaking at day 10 and remaining significantly higher than controls until death. In neonatal BN animals significantly higher levels of Fc-RFL in experimental animals were not evident as early and peaked later (day 12) in both tissue compartments but again these differences remained until death. Cytotoxic alloantisera demonstrated that on days 6, 10, and 12 most, if not all, of the Fc-RFL were host in origion in both DA and BN GVHD, with a very significant host plasma cell response in such GVHD animals. One-micron tissue section revealed the presence of a great number of plasma cell especially prominent in the medulla of lymph nodes with the cortex of lymph nodes and white pulp of the spleen markedly depleted of lymphocytes indicative of cytotoxicity."}
{"id": "PMID:1445", "title": "Kinetics of the antibody response to type III pneumococcal polysaccharide (SSS-III). I. Use of 125I-labeled SSS-III to study serum antibody levels, as well as the distribution and excretion of antigen after immunization.", "content": "A simple method was described for the preparation of 125I-labeled type III neumococcal polysaccharide (SSS-III) with a high specific radioactivity which retained the physical and immunologic properties of native SSS-III. SSS-III was used to study the serum and tissue levels of antigen, as well as its excretion, after i.p. injection. When an optimally immunogenic dose (0.5 mug) of antigen was given, greater than 90% of the injected antigen was excreted during the first 3 days after injection; however, after day 3, the SSS-III which remained in each mouse was firmly bound to various tissues, and less than 5 ng SSS-III was released into the circulation daily. SSS-III was also used in a Farr test to measure serum antibody levels; the kinetics for the appearance of PFC/spleen and serum antibody levels were measured at 24-hr intervals after immunization with 0.5 mug of antigen. Maximum PFC/spleen were observed on day 4 after immunization whereas the peak serum antibody level was seen on day 5. The decay of serum antibody level from its maximum value was much slower than that of the PFC/spleen. The data describing the distribution of SSS-III in vivo and the measurement of serum antibody levels indicated that treadmill neutralization was not a factor in determining the serum antibody levels after immunization with an optimally immunogenic dose of SSS-III.", "contents": "Kinetics of the antibody response to type III pneumococcal polysaccharide (SSS-III). I. Use of 125I-labeled SSS-III to study serum antibody levels, as well as the distribution and excretion of antigen after immunization. A simple method was described for the preparation of 125I-labeled type III neumococcal polysaccharide (SSS-III) with a high specific radioactivity which retained the physical and immunologic properties of native SSS-III. SSS-III was used to study the serum and tissue levels of antigen, as well as its excretion, after i.p. injection. When an optimally immunogenic dose (0.5 mug) of antigen was given, greater than 90% of the injected antigen was excreted during the first 3 days after injection; however, after day 3, the SSS-III which remained in each mouse was firmly bound to various tissues, and less than 5 ng SSS-III was released into the circulation daily. SSS-III was also used in a Farr test to measure serum antibody levels; the kinetics for the appearance of PFC/spleen and serum antibody levels were measured at 24-hr intervals after immunization with 0.5 mug of antigen. Maximum PFC/spleen were observed on day 4 after immunization whereas the peak serum antibody level was seen on day 5. The decay of serum antibody level from its maximum value was much slower than that of the PFC/spleen. The data describing the distribution of SSS-III in vivo and the measurement of serum antibody levels indicated that treadmill neutralization was not a factor in determining the serum antibody levels after immunization with an optimally immunogenic dose of SSS-III."}
{"id": "PMID:1446", "title": "Kinetics of the antibody response to type III pneumococcal polysaccharide. II. Factors influencing the serum antibody levels after immunization with an optimally immunogenic dose of antigen.", "content": "When the number of PFC present in the spleen was measured at 24-hr intervals after immunizing with an optimally immunogenic dose of type III pneumococcal polysaccharide (SSS-III), maximal numbers of PFC were attained 4 days after immunization; thereafter, the number of PFC decreased rapidly. By contrast, serum antibody levels, which were measured in the same mice using a Farr test, reached peak values 5 days after immunization and then declined much more slowly than did the number of PFC. Two factors were found to contribute to this disparity. First, experiments conducted with splenectomized mice showed that extrasplenic antibody synthesis, which began between days 3 and 4 after immunization and peaked on days 6 to 7, accounted for nearly one-third of the total amount of serum antibody produced. Second, the average rate of antibody synthesis by PFC increased through day 6 after immunization and then declined. Antigen-antibody dissociation tests showed that the avidity of the serum antibody obtained 4 to 7 days after immunization was the same. Moreover, during the same interval, all the antibody detected by the Farr test was of the IgM class. Thus, a change in avidity or class of immunoglobulin after day 5 did not account for the disparity observed. The clearance rate of antibody injected i.v. into nonimmune and immunized mice was studied. The data obtained indicated that accelerated clearance of antibody was occurring prior to day 3 after immunization; however, after day 3 the antibody clearance rate was constant and was the same as that found when antibody was injected into nonimmune mice. These findings affirmed the results of previous studies showing that treadmill neutralization was not important in determining the serum antibody levels present after immunization with an optimally immunogenic dose of SSS-III.", "contents": "Kinetics of the antibody response to type III pneumococcal polysaccharide. II. Factors influencing the serum antibody levels after immunization with an optimally immunogenic dose of antigen. When the number of PFC present in the spleen was measured at 24-hr intervals after immunizing with an optimally immunogenic dose of type III pneumococcal polysaccharide (SSS-III), maximal numbers of PFC were attained 4 days after immunization; thereafter, the number of PFC decreased rapidly. By contrast, serum antibody levels, which were measured in the same mice using a Farr test, reached peak values 5 days after immunization and then declined much more slowly than did the number of PFC. Two factors were found to contribute to this disparity. First, experiments conducted with splenectomized mice showed that extrasplenic antibody synthesis, which began between days 3 and 4 after immunization and peaked on days 6 to 7, accounted for nearly one-third of the total amount of serum antibody produced. Second, the average rate of antibody synthesis by PFC increased through day 6 after immunization and then declined. Antigen-antibody dissociation tests showed that the avidity of the serum antibody obtained 4 to 7 days after immunization was the same. Moreover, during the same interval, all the antibody detected by the Farr test was of the IgM class. Thus, a change in avidity or class of immunoglobulin after day 5 did not account for the disparity observed. The clearance rate of antibody injected i.v. into nonimmune and immunized mice was studied. The data obtained indicated that accelerated clearance of antibody was occurring prior to day 3 after immunization; however, after day 3 the antibody clearance rate was constant and was the same as that found when antibody was injected into nonimmune mice. These findings affirmed the results of previous studies showing that treadmill neutralization was not important in determining the serum antibody levels present after immunization with an optimally immunogenic dose of SSS-III."}
{"id": "PMID:1447", "title": "Mouse epidermal aryl hydrocarbon hydroxylase.", "content": "Mouse skin contains a NADPH-dependent, aryl hydrocarbon hydroxylase (AHH), which is inducible by polycyclic aromatic hydrocarbons. In general, unsubstituted polycyclic hydrocarbons caused a greater induction of epidermal AHH than substituted one (1,2,3,4-dibenzanthracene greater than 1,2,5,6-dibenzanthracene greater than benz (a)anthracene equal 3-methylcholanthrene greater than 7,12-dimethlbenz (a)anthracene) which did not correlate with their ability to initiate tumors in mouse skin. Two different techniques were used to isolate epidermis and similar results were obtained with both. However, the technique of isolating epidermis using a mild heat treatment required that the temperature be maintained at 52 degrees C for 30 sec. If the temperature was raised to 54 degrees C or above, there was a large reduction in the AHH activity. Isolated epidermis has 4 to 5 times the AHH activity as dermis and about twice that of whole skin. This was true for control mice or mice in which AHH was induced by pretreatment with benz(a)anthracene.", "contents": "Mouse epidermal aryl hydrocarbon hydroxylase. Mouse skin contains a NADPH-dependent, aryl hydrocarbon hydroxylase (AHH), which is inducible by polycyclic aromatic hydrocarbons. In general, unsubstituted polycyclic hydrocarbons caused a greater induction of epidermal AHH than substituted one (1,2,3,4-dibenzanthracene greater than 1,2,5,6-dibenzanthracene greater than benz (a)anthracene equal 3-methylcholanthrene greater than 7,12-dimethlbenz (a)anthracene) which did not correlate with their ability to initiate tumors in mouse skin. Two different techniques were used to isolate epidermis and similar results were obtained with both. However, the technique of isolating epidermis using a mild heat treatment required that the temperature be maintained at 52 degrees C for 30 sec. If the temperature was raised to 54 degrees C or above, there was a large reduction in the AHH activity. Isolated epidermis has 4 to 5 times the AHH activity as dermis and about twice that of whole skin. This was true for control mice or mice in which AHH was induced by pretreatment with benz(a)anthracene."}
{"id": "PMID:1448", "title": "Defects in the biochemistry of collagen in diseases of connective tissue.", "content": "The collagens are the major structural glycoproteins of connective tissues. A unique primary structure and a multiplicity of post-translational modification reactions are required for normal fibrillogenesis. The post-translational modifications include hydroxylation of prolyl and lysyl residues, glycosylation, folding of the molecule into triple-helical conformation, proteolytic conversion of precursor procollagen to collagen, and oxidative deamination of certain lysyl and hydroxylysyl residues. Any defect in the normal mechanisms responsible for the synthesis and secretion of collagen molecules or the deposition of these molecules into extracellular fibers could result in abnormal fibrillogenesis; such defects could result in a connective tissue disease. Recently, defects in the regulation of the types of collagen synthesized and in the enzymes involved in the post-translational modifications have been found in heritable diseases of connective tissue. Thus far, the primary heritable disorders of collagen metabolism in man include lysyl hydroxylase deficiency in Ehlers-Danlos syndrome type VI, p-collagen peptidase deficency in Ehlers-Danlos syndrome type VII, decreased synthesis of type III collagen in Ehlers-Danlos syndrome type IV, lysyl oxidase deficency in S-linked cutis laxa and Ehlers-Danlos syndrome type V, and decreased synthesis of type I collagen in osteogenesis imperfecta.", "contents": "Defects in the biochemistry of collagen in diseases of connective tissue. The collagens are the major structural glycoproteins of connective tissues. A unique primary structure and a multiplicity of post-translational modification reactions are required for normal fibrillogenesis. The post-translational modifications include hydroxylation of prolyl and lysyl residues, glycosylation, folding of the molecule into triple-helical conformation, proteolytic conversion of precursor procollagen to collagen, and oxidative deamination of certain lysyl and hydroxylysyl residues. Any defect in the normal mechanisms responsible for the synthesis and secretion of collagen molecules or the deposition of these molecules into extracellular fibers could result in abnormal fibrillogenesis; such defects could result in a connective tissue disease. Recently, defects in the regulation of the types of collagen synthesized and in the enzymes involved in the post-translational modifications have been found in heritable diseases of connective tissue. Thus far, the primary heritable disorders of collagen metabolism in man include lysyl hydroxylase deficiency in Ehlers-Danlos syndrome type VI, p-collagen peptidase deficency in Ehlers-Danlos syndrome type VII, decreased synthesis of type III collagen in Ehlers-Danlos syndrome type IV, lysyl oxidase deficency in S-linked cutis laxa and Ehlers-Danlos syndrome type V, and decreased synthesis of type I collagen in osteogenesis imperfecta."}
{"id": "PMID:1449", "title": "Some properties of proteolysis by polymorphonuclear leukocyte-granule extracts.", "content": "The extracts of granules of human polymorphonuclear leukocytes hydrolyzed a variety of proteins including human and bovine hemoglobin, human fibrinogen, human and bovine serum albumin, bovine elastin, and casein. The hydrolysis of all the proteins except fibrinogen and elastin was increased by addition of urea. Various inhibitors of trypsin, kallikrein, plasmin, Clr, Cls, and other proteolytic enzymes had no inhibitory effect. Slight inhibition was observed with polyanethol sulfonate and strong inhibition with normal human serum. Serum of patients with hereditary angioneurotic edema having no functional C1-esterase inhibitor was as effective in inhibiting the proteolysis as normal serum. The inhibitor was localized in 4S fractions of normal serum fractionated on Sephadex G-200. Fractionation of normal serum by ammonium sulfate precipitation, Sephadex G-200 filtration, and CM-Sephadex chromatography did not result in appearance of inhibitory activity in more than one protein peak, suggesting the possibility that only one inhibitor might be responsible. Since all fractions which contained the inhibitor of proteolysis also contained alpha1-antitrypsin, since sera of patients having low alpha1-antitrypsin levels contained less inhibitory activity, and since antibodies against alpha1-antitrypsin reversed the inhibition obtained from normal serum, the inhibition of proteolysis may be attributed to alpha1-antitrypsin.", "contents": "Some properties of proteolysis by polymorphonuclear leukocyte-granule extracts. The extracts of granules of human polymorphonuclear leukocytes hydrolyzed a variety of proteins including human and bovine hemoglobin, human fibrinogen, human and bovine serum albumin, bovine elastin, and casein. The hydrolysis of all the proteins except fibrinogen and elastin was increased by addition of urea. Various inhibitors of trypsin, kallikrein, plasmin, Clr, Cls, and other proteolytic enzymes had no inhibitory effect. Slight inhibition was observed with polyanethol sulfonate and strong inhibition with normal human serum. Serum of patients with hereditary angioneurotic edema having no functional C1-esterase inhibitor was as effective in inhibiting the proteolysis as normal serum. The inhibitor was localized in 4S fractions of normal serum fractionated on Sephadex G-200. Fractionation of normal serum by ammonium sulfate precipitation, Sephadex G-200 filtration, and CM-Sephadex chromatography did not result in appearance of inhibitory activity in more than one protein peak, suggesting the possibility that only one inhibitor might be responsible. Since all fractions which contained the inhibitor of proteolysis also contained alpha1-antitrypsin, since sera of patients having low alpha1-antitrypsin levels contained less inhibitory activity, and since antibodies against alpha1-antitrypsin reversed the inhibition obtained from normal serum, the inhibition of proteolysis may be attributed to alpha1-antitrypsin."}
{"id": "PMID:1450", "title": "Inhibition of the antibacterial activity of gentamicin by urine.", "content": "Urinary levels of antibiotics determine the outcome of treatment of most urinary tract infections. The antibacterial effect of gentamicin against Escherichia coli and Pseudomonas aeruginosa in urine was studied. With use of urinary constituents in concentrations normally found in human urine, it was shown that urine has an inhibitory effect that is dependent upon the acidity and total osmolality of the urine, as well as upon the presence of individual solutes. Up to 40 times as much gentamicin may be needed to prevent the growth of E. coli or P. aeruginosa in concentrated, acidic human urine as is required in broth. This inhibitory effect may be particularly important when urinary concentrations of gentamicin are reduced either because of a reduction in dosage or because of decreased excretion due to renal insufficiency.", "contents": "Inhibition of the antibacterial activity of gentamicin by urine. Urinary levels of antibiotics determine the outcome of treatment of most urinary tract infections. The antibacterial effect of gentamicin against Escherichia coli and Pseudomonas aeruginosa in urine was studied. With use of urinary constituents in concentrations normally found in human urine, it was shown that urine has an inhibitory effect that is dependent upon the acidity and total osmolality of the urine, as well as upon the presence of individual solutes. Up to 40 times as much gentamicin may be needed to prevent the growth of E. coli or P. aeruginosa in concentrated, acidic human urine as is required in broth. This inhibitory effect may be particularly important when urinary concentrations of gentamicin are reduced either because of a reduction in dosage or because of decreased excretion due to renal insufficiency."}
{"id": "PMID:1451", "title": "The polysaccharide capsule of Bacteroides fragilis subspecies fragilis: immunochemical and morphologic definition.", "content": "A large-molecular-weight capsular polysaccharide was isolated from strains of Bacteroides fragilis subspecies fragilis. By means of electron microscopy and staining with ruthenium red, the thick polysaccharide capsule was also visualized. With use of a radioactive antigen-binding assay, antibody to this capsular polysaccharide was demonstrated in antisera prepared in rabbits to each of eight strains of B. fragilis fragilis. Antibody of similar specificity was not found in antisera prepared to Bacteroides melaninogenicus or to strains of Bacteroides fragilis subspecies vulgatus and Bacteroides fragilis subspecies distasonis; such antibody was found in antisera to only one of two strains of Bacteroides fragilis subspecies thetaiotaomicron. The radioactive antigen-binding assay is a sensitive test for the detection of antibody to capsular polysaccharide. This polysaccharide antigen may form the basis of a serogrouping system for B. fragilis.", "contents": "The polysaccharide capsule of Bacteroides fragilis subspecies fragilis: immunochemical and morphologic definition. A large-molecular-weight capsular polysaccharide was isolated from strains of Bacteroides fragilis subspecies fragilis. By means of electron microscopy and staining with ruthenium red, the thick polysaccharide capsule was also visualized. With use of a radioactive antigen-binding assay, antibody to this capsular polysaccharide was demonstrated in antisera prepared in rabbits to each of eight strains of B. fragilis fragilis. Antibody of similar specificity was not found in antisera prepared to Bacteroides melaninogenicus or to strains of Bacteroides fragilis subspecies vulgatus and Bacteroides fragilis subspecies distasonis; such antibody was found in antisera to only one of two strains of Bacteroides fragilis subspecies thetaiotaomicron. The radioactive antigen-binding assay is a sensitive test for the detection of antibody to capsular polysaccharide. This polysaccharide antigen may form the basis of a serogrouping system for B. fragilis."}
{"id": "PMID:1452", "title": "Radioassay for serum and red cell folate.", "content": "A simple, reliable assay for serum and red cell folate is described. It uses plain untreated liquid or powdered milk, requiring no special handling or purification, as binder. Such milk makes it possible to ignore endogenous serum folate binder, since crude (but not purified) milk contains a factor which releases folate from serum binder. It simplifies counting radioactivity by employing a gamma emitting isotope of pteroylglutamic acid (PGA), namely the 125I-tyramide of PGA. Like the 3H-PGA assay of Givas and Gutcho, it permits the use of stable PGA rather than unstable methyltetrahydrofolic acid (MeTHFA) standards, because it is carried out at pH 9.3, a pH at which milk folate binder is unable to distinguish PGA from MeTHFA, which is the predominat folate in human tissues. The equipment required to do the radioassay is present in most diagnostic chemistry laboratories. Results are essentially identical to the generally accepted Lactobacillus casel microbiologic method of folate assay, except that false low results are not produced in the radioassay by antibiotics, tranquilizers, and chemotherapeutic agents. Three caveats in its use are the relative instability of 125I-PGA as compared to 3H-PGA, the fact that various powdered milks differ widely in folate-binding capacity, and that only about 60 per cent of commercially obtained skim or powdered milk preparations appear to contain the substance which splits folate from serum binder.", "contents": "Radioassay for serum and red cell folate. A simple, reliable assay for serum and red cell folate is described. It uses plain untreated liquid or powdered milk, requiring no special handling or purification, as binder. Such milk makes it possible to ignore endogenous serum folate binder, since crude (but not purified) milk contains a factor which releases folate from serum binder. It simplifies counting radioactivity by employing a gamma emitting isotope of pteroylglutamic acid (PGA), namely the 125I-tyramide of PGA. Like the 3H-PGA assay of Givas and Gutcho, it permits the use of stable PGA rather than unstable methyltetrahydrofolic acid (MeTHFA) standards, because it is carried out at pH 9.3, a pH at which milk folate binder is unable to distinguish PGA from MeTHFA, which is the predominat folate in human tissues. The equipment required to do the radioassay is present in most diagnostic chemistry laboratories. Results are essentially identical to the generally accepted Lactobacillus casel microbiologic method of folate assay, except that false low results are not produced in the radioassay by antibiotics, tranquilizers, and chemotherapeutic agents. Three caveats in its use are the relative instability of 125I-PGA as compared to 3H-PGA, the fact that various powdered milks differ widely in folate-binding capacity, and that only about 60 per cent of commercially obtained skim or powdered milk preparations appear to contain the substance which splits folate from serum binder."}
{"id": "PMID:1453", "title": "The effect of environmental pH on glycosaminoglycan metabolism by normal human chondrocytes.", "content": "The synthesis and release of sulfated glycosaminoglycans by normal human chondrocytes in culture are markedly affected by environmental pH. The biosynthetic rate is increased threefold as the pH of the growth medium is raised from 7.0 to 8.0. This coincides with a corresponding elevation in total protein and cell growth. The rate of release of newly synthesized sulfated glycosaminoglycans from the cell layer as well as their distribution between intra- and extracellular localization in the cell layer is also modulated by environmental pH. At pH 8, 35 per cent is found within the cells, this value is reduced to 13 per cent at pH 7. Pulse-chase experiments showed that previously incorporated sulfated proteoglycans were released at a faster rate at pH 7 than at pH 8. The data suggest that proton concentrations affect the biosynthesis and the mode of distribution of newly synthesized sulfated glycosaminoglycans.", "contents": "The effect of environmental pH on glycosaminoglycan metabolism by normal human chondrocytes. The synthesis and release of sulfated glycosaminoglycans by normal human chondrocytes in culture are markedly affected by environmental pH. The biosynthetic rate is increased threefold as the pH of the growth medium is raised from 7.0 to 8.0. This coincides with a corresponding elevation in total protein and cell growth. The rate of release of newly synthesized sulfated glycosaminoglycans from the cell layer as well as their distribution between intra- and extracellular localization in the cell layer is also modulated by environmental pH. At pH 8, 35 per cent is found within the cells, this value is reduced to 13 per cent at pH 7. Pulse-chase experiments showed that previously incorporated sulfated proteoglycans were released at a faster rate at pH 7 than at pH 8. The data suggest that proton concentrations affect the biosynthesis and the mode of distribution of newly synthesized sulfated glycosaminoglycans."}
{"id": "PMID:1454", "title": "Effect of PGA1, PGE2, diazoxide on myocardial contractile force.", "content": "Experiments were conducted in anesthetized dogs comparing the effects of PGA1, PGE2, and diazoxide on myocardial contractile force (MC). The three agents were given in successive bolus injections intravenously in equidepressor doses and myocardial contractile force was measured by means of a strain-gauge arch sutured onto the right ventricle. The drugs were administered before and during ganglionic (hexamethonium) and beta-blockade (practolol). Both PGA1, and PGE2 caused a marked rise in MC, 24 and 20 per cent, respectively, before blockade and 10 and 11 per cent during blockade. Diazoxide caused only a minimal rise, 0.9 per cent, before blockade and a marked fall, 27 per cent, during blockade. Diazoxide administration during left ventricular bypass indicates that the decrease in MC is not a direct result of alterations in preload or after load. It is suggested that hypertensive patients treated with autonomic blocking agents may be more susceptible to heart failure in response to diazoxide therapy.", "contents": "Effect of PGA1, PGE2, diazoxide on myocardial contractile force. Experiments were conducted in anesthetized dogs comparing the effects of PGA1, PGE2, and diazoxide on myocardial contractile force (MC). The three agents were given in successive bolus injections intravenously in equidepressor doses and myocardial contractile force was measured by means of a strain-gauge arch sutured onto the right ventricle. The drugs were administered before and during ganglionic (hexamethonium) and beta-blockade (practolol). Both PGA1, and PGE2 caused a marked rise in MC, 24 and 20 per cent, respectively, before blockade and 10 and 11 per cent during blockade. Diazoxide caused only a minimal rise, 0.9 per cent, before blockade and a marked fall, 27 per cent, during blockade. Diazoxide administration during left ventricular bypass indicates that the decrease in MC is not a direct result of alterations in preload or after load. It is suggested that hypertensive patients treated with autonomic blocking agents may be more susceptible to heart failure in response to diazoxide therapy."}
{"id": "PMID:1455", "title": "Peptide-binding macromolecules in the blood of seriously ill or mentally retarded patients.", "content": "This report describes macromolecules that bind (des-aspartic acid1)-angiotensin II, the des aspartic acid1 derivative of angiotensin I, and several biologically active and inactive analogues of these polypeptides. The macromolecules were found in the plasma of approximately 2 per cent of ambulatory adults and hospitalized children and 32 per cent of the patients at two institutions for the mentally retarded. The binding properties of these macromolecules were studied by incubating with peptides labeled with 125iodine, and separating bound from free labeled peptide using small gel filtration columns. The peptide-binding macromolecules from several patients were compared. They showed very similar specificity for a group of arginyl peptides of the des-aspartyl1-angiotensin sequence. The plasma binders differed from one another in their optimum pH and their mobility in electrophoretic fields. Those with more acid pH optima displayed more rapid electrophoretic mobility. The binders fell into two classes based on apparent molecular weight, approximately 140,000 and 250,000. Those with the higher apparent molecular weight contained a large proportion of binder that could be precipitated with antiserum to human IgA. Kinetic measurements showed that the plasma binders were somewhat heterogeneous with respect to affinity for (des-asp1)-angiotensin, with apparent association constants ranging from 10(7) to 10(8) M-1. Binding activity was labile to heat, and to treatment with pepsin or trypsin. It was inhibited by calcium, protamine, streptomycin, and some other cationic compounds. The plasma peptide binder differed in specificity and molecular weight from soluble angiotensin-binding molecules extracted from tissues, and from properties expected of a receptor for angiotensin. These macromolecules may be useful reagents for measuring (des-asp1)-angiotensins. Their presence in plasma samples may interfere with angiotensin assays in some circumstances.", "contents": "Peptide-binding macromolecules in the blood of seriously ill or mentally retarded patients. This report describes macromolecules that bind (des-aspartic acid1)-angiotensin II, the des aspartic acid1 derivative of angiotensin I, and several biologically active and inactive analogues of these polypeptides. The macromolecules were found in the plasma of approximately 2 per cent of ambulatory adults and hospitalized children and 32 per cent of the patients at two institutions for the mentally retarded. The binding properties of these macromolecules were studied by incubating with peptides labeled with 125iodine, and separating bound from free labeled peptide using small gel filtration columns. The peptide-binding macromolecules from several patients were compared. They showed very similar specificity for a group of arginyl peptides of the des-aspartyl1-angiotensin sequence. The plasma binders differed from one another in their optimum pH and their mobility in electrophoretic fields. Those with more acid pH optima displayed more rapid electrophoretic mobility. The binders fell into two classes based on apparent molecular weight, approximately 140,000 and 250,000. Those with the higher apparent molecular weight contained a large proportion of binder that could be precipitated with antiserum to human IgA. Kinetic measurements showed that the plasma binders were somewhat heterogeneous with respect to affinity for (des-asp1)-angiotensin, with apparent association constants ranging from 10(7) to 10(8) M-1. Binding activity was labile to heat, and to treatment with pepsin or trypsin. It was inhibited by calcium, protamine, streptomycin, and some other cationic compounds. The plasma peptide binder differed in specificity and molecular weight from soluble angiotensin-binding molecules extracted from tissues, and from properties expected of a receptor for angiotensin. These macromolecules may be useful reagents for measuring (des-asp1)-angiotensins. Their presence in plasma samples may interfere with angiotensin assays in some circumstances."}
{"id": "PMID:1457", "title": "The transmission of impulses in the ectodermal slow conduction system of the sea anemone Calliactis parasitica (Couch).", "content": "1. The SS 1 fatigues in response to repetitive electrical stimulation. This fatigue is manifested by an increased conduction delay and a decreased SS 1 pulse amplitude. 2. Continued repetitive stimulation leads to the failure of the system. Recovery may take many seconds. Narrow strips of column fail more rapidly than wide strips. 3. The increased conduction delay is explained in terms of a decrease in the population of spiking cells. 4. A computer model is described and analysed. It suggests that conduction between electrically coupled ectoderm cells could be the basis for the SS1. The SS 1 may have properties not so far experimentally demonstrated; for example, under certain conditions it could behave as a local system.", "contents": "The transmission of impulses in the ectodermal slow conduction system of the sea anemone Calliactis parasitica (Couch). 1. The SS 1 fatigues in response to repetitive electrical stimulation. This fatigue is manifested by an increased conduction delay and a decreased SS 1 pulse amplitude. 2. Continued repetitive stimulation leads to the failure of the system. Recovery may take many seconds. Narrow strips of column fail more rapidly than wide strips. 3. The increased conduction delay is explained in terms of a decrease in the population of spiking cells. 4. A computer model is described and analysed. It suggests that conduction between electrically coupled ectoderm cells could be the basis for the SS1. The SS 1 may have properties not so far experimentally demonstrated; for example, under certain conditions it could behave as a local system."}
{"id": "PMID:1458", "title": "Colonial conduction systems in the Anthozoa: Octocorallia.", "content": "1. The octocorals Alcyonium digitatum, Pennatula phosphorea and Virgularia mirabilis each have a through-conducting nerve net. The nerve net demonstrated electrophysiologically may well be the same as that previously shown by the use of histological techniques. 2. It exhibits both facilitation and defacilitation in the rate of conduction of pulses. 3. The distance of spread of nerve net activity is not limited by the number of stimuli applied. 4. The nerve net controls fast muscle contractions; the frequency of pulses is important in determining which muscles contract and in which sequence. 5. The nerve net is 'spontaneously' active. 6. A previously undescirbed slow system has been identified in Pennatula. It has many of the properties of slow systems in sea anemones and may well be ectodermal. It is suggested that multiple conduction systems are of common occurrence in the Anthozoa.", "contents": "Colonial conduction systems in the Anthozoa: Octocorallia. 1. The octocorals Alcyonium digitatum, Pennatula phosphorea and Virgularia mirabilis each have a through-conducting nerve net. The nerve net demonstrated electrophysiologically may well be the same as that previously shown by the use of histological techniques. 2. It exhibits both facilitation and defacilitation in the rate of conduction of pulses. 3. The distance of spread of nerve net activity is not limited by the number of stimuli applied. 4. The nerve net controls fast muscle contractions; the frequency of pulses is important in determining which muscles contract and in which sequence. 5. The nerve net is 'spontaneously' active. 6. A previously undescirbed slow system has been identified in Pennatula. It has many of the properties of slow systems in sea anemones and may well be ectodermal. It is suggested that multiple conduction systems are of common occurrence in the Anthozoa."}
{"id": "PMID:1459", "title": "Water regulation by a presumptive hormone contained in identified neurosecretory cell R15 of Aplysia.", "content": "Injection of an homogenate of identified neuron R15 into the hemocele of Aplysia produced a weight increase of 3-10% within 90 min. Control injections of several other identified neurons or of seawater, were ineffective. The weight increase occurred even when the animals were maintained in 5% hyperosmotic seawater. The activity of the R15 homogenate was retained after acidification to pH 2 and heating to 100 degrees C; but activity was destroyed by proteolytic digestion with Pronase. Dialysis in cellulose dialysis tubing resulted in a significant loss of aion on Sephadex G-50 (nominal exclusion limits 1,500-30,000 daltons), activity was present in the partially included volumes, but was absent in the totally excluded or totally included volumes. The data support the notion that R15 contains one or more hormones involved in ionic regulation or water balance. The results of bioassays of R15 extracts subjected to different treatments are consistent with the hypothesis that activity is due to one or more stable polypeptides of relatively low molecular weight.", "contents": "Water regulation by a presumptive hormone contained in identified neurosecretory cell R15 of Aplysia. Injection of an homogenate of identified neuron R15 into the hemocele of Aplysia produced a weight increase of 3-10% within 90 min. Control injections of several other identified neurons or of seawater, were ineffective. The weight increase occurred even when the animals were maintained in 5% hyperosmotic seawater. The activity of the R15 homogenate was retained after acidification to pH 2 and heating to 100 degrees C; but activity was destroyed by proteolytic digestion with Pronase. Dialysis in cellulose dialysis tubing resulted in a significant loss of aion on Sephadex G-50 (nominal exclusion limits 1,500-30,000 daltons), activity was present in the partially included volumes, but was absent in the totally excluded or totally included volumes. The data support the notion that R15 contains one or more hormones involved in ionic regulation or water balance. The results of bioassays of R15 extracts subjected to different treatments are consistent with the hypothesis that activity is due to one or more stable polypeptides of relatively low molecular weight."}
{"id": "PMID:1460", "title": "Intracellular pH transients in squid giant axons caused by CO2, NH3, and metabolic inhibitors.", "content": "The intracellular pH (pHi) of squid giant axons has been measured using glass pH microelectrodes. Resting pHi in artificial seawater (ASW) (pH 7.6-7.8) at 23 degrees C was 7.32 +/- 0.02 (7.28 if corrected for liquid junction potential). Exposure of the axon to 5% CO2 at constant external pH caused a sharp decrease in pHi, while the subsequent removal of the gas caused pHi to overshoot its initial value. If the exposure to CO2 was prolonged, two additional effects were noted: (a) during the exposure, the rapid initial fall in pHi was followed by a slow rise, and (b) after the exposure, the overshoot was greatly exaggerated. Application of external NH4Cl caused pHi to rise sharply; return to normal ASW caused pHi to return to a value below its initial one. If the exposure to NH4Cl was prolonged, two additional effects were noted: (a) during the exposure, the rapid initial rise in pHi was followed by a slow fall, and (b) after the exposure, the undershoot was greatly exaggerated. Exposure to several weak acid metabolic inhibitors caused a fall in pHi whose reversibility depended upon length of exposure. Inverting the electrochemical gradient for H+ with 100 mM K-ASW had no effect on pHi changes resulting from short-term exposure to azide. A mathematical model explains the pHi changes caused by NH4Cl on the basis of passive movements of both NH3 and NH4+. The simultaneous passive movements of CO2 and HCO3-cannot explain the results of the CO2 experiments; these data require the postulation of an active proton extrusion and/or sequestration mechanism.", "contents": "Intracellular pH transients in squid giant axons caused by CO2, NH3, and metabolic inhibitors. The intracellular pH (pHi) of squid giant axons has been measured using glass pH microelectrodes. Resting pHi in artificial seawater (ASW) (pH 7.6-7.8) at 23 degrees C was 7.32 +/- 0.02 (7.28 if corrected for liquid junction potential). Exposure of the axon to 5% CO2 at constant external pH caused a sharp decrease in pHi, while the subsequent removal of the gas caused pHi to overshoot its initial value. If the exposure to CO2 was prolonged, two additional effects were noted: (a) during the exposure, the rapid initial fall in pHi was followed by a slow rise, and (b) after the exposure, the overshoot was greatly exaggerated. Application of external NH4Cl caused pHi to rise sharply; return to normal ASW caused pHi to return to a value below its initial one. If the exposure to NH4Cl was prolonged, two additional effects were noted: (a) during the exposure, the rapid initial rise in pHi was followed by a slow fall, and (b) after the exposure, the undershoot was greatly exaggerated. Exposure to several weak acid metabolic inhibitors caused a fall in pHi whose reversibility depended upon length of exposure. Inverting the electrochemical gradient for H+ with 100 mM K-ASW had no effect on pHi changes resulting from short-term exposure to azide. A mathematical model explains the pHi changes caused by NH4Cl on the basis of passive movements of both NH3 and NH4+. The simultaneous passive movements of CO2 and HCO3-cannot explain the results of the CO2 experiments; these data require the postulation of an active proton extrusion and/or sequestration mechanism."}
{"id": "PMID:1461", "title": "Analysis of an L-histidinol-utilizing mutant of Pseudomonas aeruginosa.", "content": "Transductional analysis was applied to the Pseudomonas aeruginosa mutant PAO14 (hnc-1). This mutant can utilize L-histidinol as sole source of carbon and nitrogen and has a 60-fold increased histidinol dehydrogenase (HDH) content (Dhawale, Creaser & Loper, 1972). Transductional analysis was carried out using 18 histidine-requiring mutants to see where the hnc-1 locus maps in relation to the structural genes of histidine biosynthesis. The hnc-1 marker cotransduced with group IV genes at 97 to 100 % and not at all with group I, which is known to be the structural gene for HDH. The data obtained in the studies of Km (histidinol) and Km (NAD), and the effect of pH and temperature on the HDH activity from PAO1 and PAO14 are in full agreement with the genetic data that the hnc-1 mutation is not in the structural gene for HDH. It is suggested that hnc-1 may be a mutation in a regulatory gene affecting HDH synthesis in PAO14 and may map close to his-IV whose function in histidine biosynthesis is not known.", "contents": "Analysis of an L-histidinol-utilizing mutant of Pseudomonas aeruginosa. Transductional analysis was applied to the Pseudomonas aeruginosa mutant PAO14 (hnc-1). This mutant can utilize L-histidinol as sole source of carbon and nitrogen and has a 60-fold increased histidinol dehydrogenase (HDH) content (Dhawale, Creaser & Loper, 1972). Transductional analysis was carried out using 18 histidine-requiring mutants to see where the hnc-1 locus maps in relation to the structural genes of histidine biosynthesis. The hnc-1 marker cotransduced with group IV genes at 97 to 100 % and not at all with group I, which is known to be the structural gene for HDH. The data obtained in the studies of Km (histidinol) and Km (NAD), and the effect of pH and temperature on the HDH activity from PAO1 and PAO14 are in full agreement with the genetic data that the hnc-1 mutation is not in the structural gene for HDH. It is suggested that hnc-1 may be a mutation in a regulatory gene affecting HDH synthesis in PAO14 and may map close to his-IV whose function in histidine biosynthesis is not known."}
{"id": "PMID:1462", "title": "Studies on the rumen flagellate Neocallimastix frontalis.", "content": "The vast increase in the population density of the rumen flagellate Neocallimastix frontalis shortly after the host animal has commenced eating is caused by stimulation of a reproductive body on a vegetative phase of the organism to differentiate and liberate the flagellates. The stimulant is a component of the host's diet. The vegetative stage of N. frontalis bears a strong morphological resemblance to that of certain species of aquatic phycomycete fungi, and consists of a reproductive body borne on  a single, much branched rhizoid. The flagellates liberated in vivo within 15 to 45 min of feeding lose their motility within I h and develop into the vegetative phase, thus producing a rapid decrease in population density of the flagellates. Conditions for maximum flagellate production are similar to those occurring in the rumen: pH 6-5, 39 degrees C, absence of O2, presence of CO2. Differentiation of the reproductive body is inhibited by compounds affecting membrane structure and function, but not by inhibitors of protein synthesis. The organism was cultured in vitro in an undefined medium in the absence of bacteria or other flagellates.", "contents": "Studies on the rumen flagellate Neocallimastix frontalis. The vast increase in the population density of the rumen flagellate Neocallimastix frontalis shortly after the host animal has commenced eating is caused by stimulation of a reproductive body on a vegetative phase of the organism to differentiate and liberate the flagellates. The stimulant is a component of the host's diet. The vegetative stage of N. frontalis bears a strong morphological resemblance to that of certain species of aquatic phycomycete fungi, and consists of a reproductive body borne on  a single, much branched rhizoid. The flagellates liberated in vivo within 15 to 45 min of feeding lose their motility within I h and develop into the vegetative phase, thus producing a rapid decrease in population density of the flagellates. Conditions for maximum flagellate production are similar to those occurring in the rumen: pH 6-5, 39 degrees C, absence of O2, presence of CO2. Differentiation of the reproductive body is inhibited by compounds affecting membrane structure and function, but not by inhibitors of protein synthesis. The organism was cultured in vitro in an undefined medium in the absence of bacteria or other flagellates."}
{"id": "PMID:1463", "title": "Properties of some bacteriocins produced by Rhizobium trifolii.", "content": "Bacteriocins produced by six strains of Rhizobium trifolii were found to be of the relatively low molecular weight, non-phage type. The molecular weights ranged from approximately 1-8 X 105 to 2-0 X 105. All were of protein composition, as indicated by buoyant density (1-32 to 1-34 g/cm3) in CsC1 and by sensitivity to proteolytic enzymes. They were resistant to RNAase but sensitive to DNAase. The six bacteriocins could further be separated into two subgroups on the basis of sensitivity to extremes of pH, binding to filter membranes, activity spectrum on sensitive strains of R. trifolii, and possibly mode of action on sensitive bacteria. Bacteriocin production occurred spontaneously during the early-to mid-exponential phase of bacterial growth in broth culture.", "contents": "Properties of some bacteriocins produced by Rhizobium trifolii. Bacteriocins produced by six strains of Rhizobium trifolii were found to be of the relatively low molecular weight, non-phage type. The molecular weights ranged from approximately 1-8 X 105 to 2-0 X 105. All were of protein composition, as indicated by buoyant density (1-32 to 1-34 g/cm3) in CsC1 and by sensitivity to proteolytic enzymes. They were resistant to RNAase but sensitive to DNAase. The six bacteriocins could further be separated into two subgroups on the basis of sensitivity to extremes of pH, binding to filter membranes, activity spectrum on sensitive strains of R. trifolii, and possibly mode of action on sensitive bacteria. Bacteriocin production occurred spontaneously during the early-to mid-exponential phase of bacterial growth in broth culture."}
{"id": "PMID:1465", "title": "Production and purification of the gamma haemolysin of Staphylococcus aureus 'Smith 5R'.", "content": "The gamma haemolysin of Staphylococcus aureus 'Smith 5R' was produced on Dolman-Wilson agar overlain with cellophane. Maximal yields of crude lysin with titres of 2000 to 4000 haemolytic units/ml were obtained within 24 h at 37 degrees C in 10% (v/v) CO2 in air, on medium adjusted to pH 7-0. The crude lysin was purified 2700-fold (with 75% recovery) by ultrafiltration, gel filtration and ammonium sulphate fractionation. The specific activity of the lysin was 10(5) haemolytic units/mg protein after the dialysed active precipitate was extracted with NaCl and reprecipitated with ammonium sulphate. Purified gamma lysin was homogeneous by disc electrophoresis and immunoelectrophoresis.", "contents": "Production and purification of the gamma haemolysin of Staphylococcus aureus 'Smith 5R'. The gamma haemolysin of Staphylococcus aureus 'Smith 5R' was produced on Dolman-Wilson agar overlain with cellophane. Maximal yields of crude lysin with titres of 2000 to 4000 haemolytic units/ml were obtained within 24 h at 37 degrees C in 10% (v/v) CO2 in air, on medium adjusted to pH 7-0. The crude lysin was purified 2700-fold (with 75% recovery) by ultrafiltration, gel filtration and ammonium sulphate fractionation. The specific activity of the lysin was 10(5) haemolytic units/mg protein after the dialysed active precipitate was extracted with NaCl and reprecipitated with ammonium sulphate. Purified gamma lysin was homogeneous by disc electrophoresis and immunoelectrophoresis."}
{"id": "PMID:1466", "title": "Basic and neutral amino acid transport in Aspergillus nidulans.", "content": "Arginine and methionine transport by Aspergillus nidulans mycelium was investigated. A single uptake system is responsible for the transport of arginine, lysine and ornithine. Transport is energy-dependent and specific for these basic amino acids. The Km value for arginine is 1 X 10(-5) M, and Vmax is 2-8 nmol/mg dry wt/min; Km for lysine is 8 X 10(-6) M; Kt for lysine as inhibitor of arginine uptake is 12 muM, and Ki for ornithine is mM. On minimal medium, methionine is transported with a Km of 0-I mM and Vmax about I nmol/mg dry wt/min; transport is inhibited by azide. Neutral amnio acids such as serine, phenylalanine and leucine are probably transported by the same system, as indicated by their inhibition of methionine uptake and the existence of a mutant specifically impaired in their transport. The recessive mutant nap3, unable to transport neutral amino acids, was isolated as resistant to selenomethionine and p-fluorophenylanine. This mutant has unchanged transport of methionine by general and specific sulphur-regulated permeases.", "contents": "Basic and neutral amino acid transport in Aspergillus nidulans. Arginine and methionine transport by Aspergillus nidulans mycelium was investigated. A single uptake system is responsible for the transport of arginine, lysine and ornithine. Transport is energy-dependent and specific for these basic amino acids. The Km value for arginine is 1 X 10(-5) M, and Vmax is 2-8 nmol/mg dry wt/min; Km for lysine is 8 X 10(-6) M; Kt for lysine as inhibitor of arginine uptake is 12 muM, and Ki for ornithine is mM. On minimal medium, methionine is transported with a Km of 0-I mM and Vmax about I nmol/mg dry wt/min; transport is inhibited by azide. Neutral amnio acids such as serine, phenylalanine and leucine are probably transported by the same system, as indicated by their inhibition of methionine uptake and the existence of a mutant specifically impaired in their transport. The recessive mutant nap3, unable to transport neutral amino acids, was isolated as resistant to selenomethionine and p-fluorophenylanine. This mutant has unchanged transport of methionine by general and specific sulphur-regulated permeases."}
{"id": "PMID:1467", "title": "Polyamino acid induced aphid transmission of plant viruses.", "content": "Aphids transmitted poly-L-ornithine (PLO)-treated tobacco mosaic virus (TMV) when given acquistion and inoculation access periods as brief as 30 s and 2 min, respectively; the ability to transmit was lost within 90 min. Aphids without claws were able to transmit the virus. Transmission thus seems similar to that of nonpersistent viruses. The ratio of virus to polyamino acid, as well as the KCl concentration, markedly affected transmission. Transmission was best from mixtures which contained 250 mug/ml TMV, 2-5 MUG/ML PLO (mol. wt. 120000) and 0-6 M-KCl. A similar mixture favoured transmission when poly-L-lysine (mol. wt. 85000) was substituted for PLO, but with poly-L-lysine (mol. wt. 30 000) it was necessary to decrease the KCl to 0-3 M to obtain transmission. Less KCl (0-08 to 0-24 M) also favoured aphid transmission of PLO-treated potato virus X and tobacco rattle virus. PLO-treated TMV ultracentrifuged in the presence of, and resuspended in, 0-6 M-KCl remained aphid  transmissible while PLO-treated virus in 2 M-DCl, which favours greater dissociation of the virus-PLO complex, was transmissible neither before nor after sedimentation by ultracentrifuging, and resuspension in 0-6 M-KCl. these results show that transmissibility is not due to a permanent alteration of the virus by PLO and indicate that the formation of a TMV-PLO complex is required for transmission. Sequential acquisition experiments suggest that PLO may act by binding TMV to receptor sites in aphids. However, the possibility that PLO affects the infection process was not ruled out.", "contents": "Polyamino acid induced aphid transmission of plant viruses. Aphids transmitted poly-L-ornithine (PLO)-treated tobacco mosaic virus (TMV) when given acquistion and inoculation access periods as brief as 30 s and 2 min, respectively; the ability to transmit was lost within 90 min. Aphids without claws were able to transmit the virus. Transmission thus seems similar to that of nonpersistent viruses. The ratio of virus to polyamino acid, as well as the KCl concentration, markedly affected transmission. Transmission was best from mixtures which contained 250 mug/ml TMV, 2-5 MUG/ML PLO (mol. wt. 120000) and 0-6 M-KCl. A similar mixture favoured transmission when poly-L-lysine (mol. wt. 85000) was substituted for PLO, but with poly-L-lysine (mol. wt. 30 000) it was necessary to decrease the KCl to 0-3 M to obtain transmission. Less KCl (0-08 to 0-24 M) also favoured aphid transmission of PLO-treated potato virus X and tobacco rattle virus. PLO-treated TMV ultracentrifuged in the presence of, and resuspended in, 0-6 M-KCl remained aphid  transmissible while PLO-treated virus in 2 M-DCl, which favours greater dissociation of the virus-PLO complex, was transmissible neither before nor after sedimentation by ultracentrifuging, and resuspension in 0-6 M-KCl. these results show that transmissibility is not due to a permanent alteration of the virus by PLO and indicate that the formation of a TMV-PLO complex is required for transmission. Sequential acquisition experiments suggest that PLO may act by binding TMV to receptor sites in aphids. However, the possibility that PLO affects the infection process was not ruled out."}
{"id": "PMID:1468", "title": "Disruption of Vi bacteriophage III and localization of its deacetylase activity.", "content": "It has been shown that particles of Vi bacteriophage III catalyse deacetylation of O-acetyl pectic (polygalacturonic) acid, a structural analogue of Vi polysaccharide (Vi antigen). Using this substrate, and determining the acetic acid liberated by gas-liquid chromatogrphy, a method for the estimation of Vi phage deacetylase activity has been developed. Purified particles of Vi phage III were exposed to a variety of mildly dissociative reagents and conditions, and then tested for plaque-forming and for deacetylase activity. They have also been inspected under the electron microscope. Osmotic shock, and incubation in the presence of ethylenediamine tetraacetic acid (greater than or equil 0-01 M), or of L-arginine (0-25 M), were found to cause disintegration of the virions into empty head capsids, deoxyribonucleic acid, and base plates still carrying the spikes. The mixtures of viral fragments exhibited an increased deacetylase activity. Using zonal sedimentation and ion exchange chromatography, the phage fragments obtained by treatment with ethylenediaminetetraacetic acid have been fractionated and the base plates isolated. Amongst the viral components, these structures showed the highest specific deacetylase activity. They had the shape of six-pointed stars (about 9-5 nm inner, and 14-5 nm outer diam.) with a central hole or plug (approximately 3 nm), carrying six spikes, roughly cylindrical organelles of approx. 11 X 4 nm, one at each of the points. Of the polypeptides of six sizes (P.1, about 153,000 daltons; P.2, 91,000; P.3, 71,000; P.4 56,500; P.6, 22,000), detected in whole Vi phage III virions by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, only two, P.2 and P.3 were found in the base plates.", "contents": "Disruption of Vi bacteriophage III and localization of its deacetylase activity. It has been shown that particles of Vi bacteriophage III catalyse deacetylation of O-acetyl pectic (polygalacturonic) acid, a structural analogue of Vi polysaccharide (Vi antigen). Using this substrate, and determining the acetic acid liberated by gas-liquid chromatogrphy, a method for the estimation of Vi phage deacetylase activity has been developed. Purified particles of Vi phage III were exposed to a variety of mildly dissociative reagents and conditions, and then tested for plaque-forming and for deacetylase activity. They have also been inspected under the electron microscope. Osmotic shock, and incubation in the presence of ethylenediamine tetraacetic acid (greater than or equil 0-01 M), or of L-arginine (0-25 M), were found to cause disintegration of the virions into empty head capsids, deoxyribonucleic acid, and base plates still carrying the spikes. The mixtures of viral fragments exhibited an increased deacetylase activity. Using zonal sedimentation and ion exchange chromatography, the phage fragments obtained by treatment with ethylenediaminetetraacetic acid have been fractionated and the base plates isolated. Amongst the viral components, these structures showed the highest specific deacetylase activity. They had the shape of six-pointed stars (about 9-5 nm inner, and 14-5 nm outer diam.) with a central hole or plug (approximately 3 nm), carrying six spikes, roughly cylindrical organelles of approx. 11 X 4 nm, one at each of the points. Of the polypeptides of six sizes (P.1, about 153,000 daltons; P.2, 91,000; P.3, 71,000; P.4 56,500; P.6, 22,000), detected in whole Vi phage III virions by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, only two, P.2 and P.3 were found in the base plates."}
{"id": "PMID:1469", "title": "A model to replace psychiatric hospitals.", "content": "A comprehensive system of community treatment in southwest Denver has reduced the need for adult psychiatric inpatient beds to less than 1/100,000 population. Six small, community-based therapeutic environments, crisis intervention, home treatment, social systems intervention, and rapid tranquilization comprise the essential components of this total community care system. The system operates within a framework of citizen participation and community control, the elimination of formal staff offices, and a focus on working in the real-life setting of the client and his family. To evaluate the effectiveness of community care, patients about to be hospitalized were randomly assigned to a psychiatric hospital or to community alternative treatment. Outcome measures at discharge and at follow-up completed by the client himself, treatment staff, and family members indicate that community treatment was more effective than psychiatric hospitalization.", "contents": "A model to replace psychiatric hospitals. A comprehensive system of community treatment in southwest Denver has reduced the need for adult psychiatric inpatient beds to less than 1/100,000 population. Six small, community-based therapeutic environments, crisis intervention, home treatment, social systems intervention, and rapid tranquilization comprise the essential components of this total community care system. The system operates within a framework of citizen participation and community control, the elimination of formal staff offices, and a focus on working in the real-life setting of the client and his family. To evaluate the effectiveness of community care, patients about to be hospitalized were randomly assigned to a psychiatric hospital or to community alternative treatment. Outcome measures at discharge and at follow-up completed by the client himself, treatment staff, and family members indicate that community treatment was more effective than psychiatric hospitalization."}
{"id": "PMID:1473", "title": "Dynamic changes in regional CBF, intraventricular pressure, CSF pH and lactate levels during the acute phase of head injury.", "content": "The authors measured regional cerebral 133xenon (133Xe) blood flow (rCBF), intraventricular pressure (IVP), cerebrospinal fluid (CSF) pH and lactate, systemic arterial blood pressure (SAP), and arterial blood gases during the acute phase in 23 comatose patients with severe head injuries. The IVP was kept below 45 mm Hg. The rCBF was measured repeatedly, and the response to induced hypertension and hyperventilation was tested. Most patients had reduced rCBF. No correlation was found between average CBF and clinical condition, and neither global nor regional ischemia contributed significantly to the reduced brain function. No correlation was found between CBF and IVP or CBF and cerebral perfusion pressure (CPP). The CSF lactate was elevated significantly in patients with brain-stem lesions, but not in patients with \"pure\" cortical lesiosn. The 133Xe clearance curves from areas of severe cortical lesions had very fast initial components called tissue peaks. The tissue peak areas correlated with areas of early veins in the angiograms, indicating a state of relative hyperemia, referred to as tissue-peak hyperemia. Tissue-peak hyperemia was found in all patients with cortical laceration or severe contusion but not in patients with brain-stem lesions without such cortical lesions. The peaks increased in number during clinical deterioration and disappeared during improvement. They could be provoked by induced hypertension and disappeared during hyperventilation. The changes in the tissue-peak areas appeared to be related to the clinical course of the cortical lesion.", "contents": "Dynamic changes in regional CBF, intraventricular pressure, CSF pH and lactate levels during the acute phase of head injury. The authors measured regional cerebral 133xenon (133Xe) blood flow (rCBF), intraventricular pressure (IVP), cerebrospinal fluid (CSF) pH and lactate, systemic arterial blood pressure (SAP), and arterial blood gases during the acute phase in 23 comatose patients with severe head injuries. The IVP was kept below 45 mm Hg. The rCBF was measured repeatedly, and the response to induced hypertension and hyperventilation was tested. Most patients had reduced rCBF. No correlation was found between average CBF and clinical condition, and neither global nor regional ischemia contributed significantly to the reduced brain function. No correlation was found between CBF and IVP or CBF and cerebral perfusion pressure (CPP). The CSF lactate was elevated significantly in patients with brain-stem lesions, but not in patients with \"pure\" cortical lesiosn. The 133Xe clearance curves from areas of severe cortical lesions had very fast initial components called tissue peaks. The tissue peak areas correlated with areas of early veins in the angiograms, indicating a state of relative hyperemia, referred to as tissue-peak hyperemia. Tissue-peak hyperemia was found in all patients with cortical laceration or severe contusion but not in patients with brain-stem lesions without such cortical lesions. The peaks increased in number during clinical deterioration and disappeared during improvement. They could be provoked by induced hypertension and disappeared during hyperventilation. The changes in the tissue-peak areas appeared to be related to the clinical course of the cortical lesion."}
{"id": "PMID:1478", "title": "Nursing deans as leaders in collegiate health professions.", "content": "Deans of Nursing who choose to be administrators of the Health Sciences may very well enhance Nursing programs by facilitating the nursing faculty to become leaders through offering service courses in Health, may thereby help to cut the high cost of nursing education, and may make a contribution to other Health majors by sharing their faculty's special expertise in Health theory.", "contents": "Nursing deans as leaders in collegiate health professions. Deans of Nursing who choose to be administrators of the Health Sciences may very well enhance Nursing programs by facilitating the nursing faculty to become leaders through offering service courses in Health, may thereby help to cut the high cost of nursing education, and may make a contribution to other Health majors by sharing their faculty's special expertise in Health theory."}
{"id": "PMID:1480", "title": "Studies of the effect of dietary cholesterol on hepatic protein synthesis, reduced glutathione levels and serine dehydratase activity in the rat.", "content": "A basal diet or a basal diet plus 1% of cholesterol and 0.33% cholic acid was fed to rats for varying lengths of time and (1) the activities of liver phosphoenolpyruvate-carboxykinase (PEP-CK), tyrosine transaminase (TT), and serine dehydratase (SD); (2) the rate of total hepatic protein synthesis and (3) the concentration of hepatic reduced glutathione (GSH) were quantitated. The specific activity of PEP-CK was significantly depressed by cholesterol plus cholic acid feeding, while the specific activity of TT was unchanged. No significant effect of dietary cholesterol plus cholic acid was found on the total liver activities. In contrast, SD specific activity was increased 3-fold. The rate of (U-14C)-L-leucine incorporation into total TCA precipitable protein following ingestion of cholesterol plus acid was significantly reduced when the data were expressed as dpm (U-14C)-L-leucine/mg protein. After correcting this expression for specific radioactivity of the liver tissue free leucine pool, no significant effect of dietary cholesterol plus cholic acid on hepatic protein synthesis existed. In fact, the amount of 14C-leucine incorporated into protein on a total liver basis was 50% greater for the cholesterol group. On a per gram of liver basis, the concentration of GSH in the liver of rats fed a cholesterol plus cholic acid diet was significantly decreased. Considering the liver enlargement in rats fed cholesterol plus cholic acid, total organ GSH was found to be significantly greater than for rats fed a basal diet.", "contents": "Studies of the effect of dietary cholesterol on hepatic protein synthesis, reduced glutathione levels and serine dehydratase activity in the rat. A basal diet or a basal diet plus 1% of cholesterol and 0.33% cholic acid was fed to rats for varying lengths of time and (1) the activities of liver phosphoenolpyruvate-carboxykinase (PEP-CK), tyrosine transaminase (TT), and serine dehydratase (SD); (2) the rate of total hepatic protein synthesis and (3) the concentration of hepatic reduced glutathione (GSH) were quantitated. The specific activity of PEP-CK was significantly depressed by cholesterol plus cholic acid feeding, while the specific activity of TT was unchanged. No significant effect of dietary cholesterol plus cholic acid was found on the total liver activities. In contrast, SD specific activity was increased 3-fold. The rate of (U-14C)-L-leucine incorporation into total TCA precipitable protein following ingestion of cholesterol plus acid was significantly reduced when the data were expressed as dpm (U-14C)-L-leucine/mg protein. After correcting this expression for specific radioactivity of the liver tissue free leucine pool, no significant effect of dietary cholesterol plus cholic acid on hepatic protein synthesis existed. In fact, the amount of 14C-leucine incorporated into protein on a total liver basis was 50% greater for the cholesterol group. On a per gram of liver basis, the concentration of GSH in the liver of rats fed a cholesterol plus cholic acid diet was significantly decreased. Considering the liver enlargement in rats fed cholesterol plus cholic acid, total organ GSH was found to be significantly greater than for rats fed a basal diet."}
{"id": "PMID:1481", "title": "Thiamine triphosphatase activity of myosin and accelerating effect of thiamine di- and tri-phosphates on superprecipitation of actomyosin.", "content": "TTP accelerated ATP-induced superprecipitation of actomyosin in as low a concentration as 30 muM and decreased light scattering by actomyosin. These effects could also be observed in the same way, but to a lesser degree, by addition to TDP. Myosin was able to hydrolyze TTP to TDP, but some important differences were confirmed between myosin TTPase and ATPase. Myosin TTPase was inhibited by actin and showed a much larger Km than that of ATPase. TTP significantly inhibited myosin B ATPase and ATP greatly inhibited myosin B TTPase. These findings suggest that the accelerating effect of TDP and TTP may be due to the binding of thiamine phosphate to the regulatory site of myosin followed by a change in its physical chemical property, rather than due to the competitive binding of thiamine phosphate to the catalytically activity site of myosin.", "contents": "Thiamine triphosphatase activity of myosin and accelerating effect of thiamine di- and tri-phosphates on superprecipitation of actomyosin. TTP accelerated ATP-induced superprecipitation of actomyosin in as low a concentration as 30 muM and decreased light scattering by actomyosin. These effects could also be observed in the same way, but to a lesser degree, by addition to TDP. Myosin was able to hydrolyze TTP to TDP, but some important differences were confirmed between myosin TTPase and ATPase. Myosin TTPase was inhibited by actin and showed a much larger Km than that of ATPase. TTP significantly inhibited myosin B ATPase and ATP greatly inhibited myosin B TTPase. These findings suggest that the accelerating effect of TDP and TTP may be due to the binding of thiamine phosphate to the regulatory site of myosin followed by a change in its physical chemical property, rather than due to the competitive binding of thiamine phosphate to the catalytically activity site of myosin."}
{"id": "PMID:1483", "title": "The meaning of the Leydig cell in relation to the etiology of cryptorchidism: An experimental electron-microscopic study.", "content": "In our electron-microscopic studies of testicular biopsies, both normal and cryptorchid, we found a simple atrophy of the Leydig cell in the cryptorchid testis. Based on experiments by Raynaud1,2 and Jean3 on pregnant mice, we tried to find the reason for changes in the Leydig cell relating to the etiology of cryptorchidism. We found on electron microscopic study of testes in the offspring of pregnant mice treated with estrogen the same atrophy of the Leydig cell as we see in human cryptorchidism. These changes are not evident when estrogen and HCG are given together. We can conclude from this experiment that lack of gonadotropin stimulation leads to the atrophy of Leydig cells. This atrophy then produces a lack of androgen which could be responsible for cryptorchidism.", "contents": "The meaning of the Leydig cell in relation to the etiology of cryptorchidism: An experimental electron-microscopic study. In our electron-microscopic studies of testicular biopsies, both normal and cryptorchid, we found a simple atrophy of the Leydig cell in the cryptorchid testis. Based on experiments by Raynaud1,2 and Jean3 on pregnant mice, we tried to find the reason for changes in the Leydig cell relating to the etiology of cryptorchidism. We found on electron microscopic study of testes in the offspring of pregnant mice treated with estrogen the same atrophy of the Leydig cell as we see in human cryptorchidism. These changes are not evident when estrogen and HCG are given together. We can conclude from this experiment that lack of gonadotropin stimulation leads to the atrophy of Leydig cells. This atrophy then produces a lack of androgen which could be responsible for cryptorchidism."}
{"id": "PMID:1486", "title": "The in vitro adsorption of drugs from horse serum onto carbon coated with an acrylic hydrogel.", "content": "In vitro studies have shown that uncoated carbon and carbon coated with an acrylic hydrogel are capable of adsorbing drugs from horse serum at 37 degrees. Increase in the coating weight from 2 to 4% decreased the rate of adsorption but not the total capacity. In vivo data supports the concept of carbon haemoperfusion for use in the treatment of drug overdose.", "contents": "The in vitro adsorption of drugs from horse serum onto carbon coated with an acrylic hydrogel. In vitro studies have shown that uncoated carbon and carbon coated with an acrylic hydrogel are capable of adsorbing drugs from horse serum at 37 degrees. Increase in the coating weight from 2 to 4% decreased the rate of adsorption but not the total capacity. In vivo data supports the concept of carbon haemoperfusion for use in the treatment of drug overdose."}
{"id": "PMID:1487", "title": "The interaction of antihistamines with lecithin monolayers.", "content": "The interaction of a series of antihistamines with monolayers of L-alpha-dipalmitoyl lecithin has been examined. An increase in the monolayer surface pressure was noted for monolayers spread on the antihistamine solutions, suggesting penetration of the film by drug molecules. At high surface pressures there was an apparent ejection of drug molecules from the film. The ability of the antihistamines to increase surface pressure was correlated with their surface activity at the air-solution interface. The effect of drug concentration on the magnitude of the surface pressure was examined for diphenhydramine hydrochloride. Application of the Gibbs adsorption equation at low surface compressions indicated an approximate area per molecule for diphenhydramine in the film which was in good agreement with the value previously obtained at the air-solution interface. Preliminary measurements showed that the surface pressure increase was larger in the presence of phosphate buffer at pH 6-8. It was not clear whether this effect was caused by the buffer components or was a pH effect.", "contents": "The interaction of antihistamines with lecithin monolayers. The interaction of a series of antihistamines with monolayers of L-alpha-dipalmitoyl lecithin has been examined. An increase in the monolayer surface pressure was noted for monolayers spread on the antihistamine solutions, suggesting penetration of the film by drug molecules. At high surface pressures there was an apparent ejection of drug molecules from the film. The ability of the antihistamines to increase surface pressure was correlated with their surface activity at the air-solution interface. The effect of drug concentration on the magnitude of the surface pressure was examined for diphenhydramine hydrochloride. Application of the Gibbs adsorption equation at low surface compressions indicated an approximate area per molecule for diphenhydramine in the film which was in good agreement with the value previously obtained at the air-solution interface. Preliminary measurements showed that the surface pressure increase was larger in the presence of phosphate buffer at pH 6-8. It was not clear whether this effect was caused by the buffer components or was a pH effect."}
{"id": "PMID:1488", "title": "Effect of surfactant monomers on chloramphenicol association to an albumin-lecithin complex: a model for modified drug absorption.", "content": "The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation.", "contents": "Effect of surfactant monomers on chloramphenicol association to an albumin-lecithin complex: a model for modified drug absorption. The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation."}
{"id": "PMID:1489", "title": "The effect of blending on the rheological properties of gelatin solutions and gels.", "content": "The effect of blending on rheological properties for an acid and alkaline processed gelatin has been investigated. Blending of weak gels (1-0-3-5% w/v at 25 degrees), resulted in a decrease in gel rigidity whereas in the stronger gels (5-50% w/v at 25 degrees) and solutions (18% and 30% w/v at 35 degrees), an increase occurred. The decrease in structure in the weak gels is considered to be due to coulombic effects, minimum strength occurring for a mixture which possessed zero charge in solution. A tentative explanation for effects in rigid gels and concentrated solutions is offered.", "contents": "The effect of blending on the rheological properties of gelatin solutions and gels. The effect of blending on rheological properties for an acid and alkaline processed gelatin has been investigated. Blending of weak gels (1-0-3-5% w/v at 25 degrees), resulted in a decrease in gel rigidity whereas in the stronger gels (5-50% w/v at 25 degrees) and solutions (18% and 30% w/v at 35 degrees), an increase occurred. The decrease in structure in the weak gels is considered to be due to coulombic effects, minimum strength occurring for a mixture which possessed zero charge in solution. A tentative explanation for effects in rigid gels and concentrated solutions is offered."}
{"id": "PMID:1490", "title": "Amphetamine tachyphylaxis in the pithed guinea-pig.", "content": "A single dose of (+)-amphetamine (8 mg kg-1, i.p.) administered 4 h before experimentation, reduced the pressor and positive chronotropic effects elicited by this drug (0-6 mg kg-1, i.v.) and augmented the rate of the development of tachyphylaxis to these responses in the pithed guinea-pig preparation. Amphetamine pretreatment reduced the pressor and positive chronotropic effects of phenylephrine (0-1 mg kg-1, i.v.) and the positive chronotropic effects of angiotensin (30 mug kg-1, i.v.). The rate of the development of tachyphylaxis to the cardiovascular responses elicited by phenylephrine and angiotensin was augmented by amphetamine pretreatment. The results suggest that an indirect mechanism (noradrenaline) may in part mediate the cardiovascular effects of these 3 drugs and/or that amphetamine may act as a competitive antagonist at adrenoceptor sites.", "contents": "Amphetamine tachyphylaxis in the pithed guinea-pig. A single dose of (+)-amphetamine (8 mg kg-1, i.p.) administered 4 h before experimentation, reduced the pressor and positive chronotropic effects elicited by this drug (0-6 mg kg-1, i.v.) and augmented the rate of the development of tachyphylaxis to these responses in the pithed guinea-pig preparation. Amphetamine pretreatment reduced the pressor and positive chronotropic effects of phenylephrine (0-1 mg kg-1, i.v.) and the positive chronotropic effects of angiotensin (30 mug kg-1, i.v.). The rate of the development of tachyphylaxis to the cardiovascular responses elicited by phenylephrine and angiotensin was augmented by amphetamine pretreatment. The results suggest that an indirect mechanism (noradrenaline) may in part mediate the cardiovascular effects of these 3 drugs and/or that amphetamine may act as a competitive antagonist at adrenoceptor sites."}
{"id": "PMID:1491", "title": "Phenylbutazone-warfarin interaction in the dog.", "content": "The administration of phenylbutazone together with warfarin to dogs resulted in an elevation of the free fraction of warfarin in the plasma from 2-6 to 8-0% thus providing direct support for the notion that phenylbutazone induced inhibition of warfarin binding to plasma proteins. This inhibition as evaluated by a kinetic method was accompanied by a two-fold decrease in the plasma half-life of warfarin from 18-4 h in control animals to 9-6 h in phenylbutazone-treated animals. Marked increases in warfarin-induced hypoprothrombinaemia were observed when at doses up to 8 mg kg-1 (orally) it was given with phenylbutazone (50 mg kg-1, orally). The unbound fraction of warfarin in canine plasma ranged from 1-7 to 4-3% indicating individual differences in the extent of the plasma binding of warfarin in the dog.", "contents": "Phenylbutazone-warfarin interaction in the dog. The administration of phenylbutazone together with warfarin to dogs resulted in an elevation of the free fraction of warfarin in the plasma from 2-6 to 8-0% thus providing direct support for the notion that phenylbutazone induced inhibition of warfarin binding to plasma proteins. This inhibition as evaluated by a kinetic method was accompanied by a two-fold decrease in the plasma half-life of warfarin from 18-4 h in control animals to 9-6 h in phenylbutazone-treated animals. Marked increases in warfarin-induced hypoprothrombinaemia were observed when at doses up to 8 mg kg-1 (orally) it was given with phenylbutazone (50 mg kg-1, orally). The unbound fraction of warfarin in canine plasma ranged from 1-7 to 4-3% indicating individual differences in the extent of the plasma binding of warfarin in the dog."}
{"id": "PMID:1492", "title": "The effect of pancuronium on myocardial contraction and catecholamine metabolism.", "content": "The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to \"rebound\" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate \"rebound.\"", "contents": "The effect of pancuronium on myocardial contraction and catecholamine metabolism. The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to \"rebound\" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate \"rebound.\""}
{"id": "PMID:1493", "title": "Metabolism of delta1-tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism.", "content": "The metabolism of (-)-delta1-tetrahydrocannabinol (delta1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-delta1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC was also present together with small amounts of 6alpha-hydroxy-delta1-THC and 6beta-hydroxy-delta1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6beta-hydroxy-delta1-THC and 6alpha-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of delta1-THC.", "contents": "Metabolism of delta1-tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism. The metabolism of (-)-delta1-tetrahydrocannabinol (delta1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-delta1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC was also present together with small amounts of 6alpha-hydroxy-delta1-THC and 6beta-hydroxy-delta1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6beta-hydroxy-delta1-THC and 6alpha-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of delta1-THC."}
{"id": "PMID:1494", "title": "Determination of low cencentrations of the quaternary ammonium compound thiazinamium methylsulphate in plasma and urine.", "content": "A sensitive and selective method for the quantitative determination of the quaternary ammonium antiacetylcholine-compound thiazinamium methylsulphate (Multergan) in plasma and urine is described. The procedure is based on ion pair extraction of the compound with iodide as the counter ion. This is followed by gas chromatography using an alkali flame ionization detector. The detection limit is 2 ng ml-1 with a recovery of 88-0 +/- 6-2% from plasma, 91-4 +/- 4-6% from urine. The described method can also be applied to other quaternary ammonium compounds.", "contents": "Determination of low cencentrations of the quaternary ammonium compound thiazinamium methylsulphate in plasma and urine. A sensitive and selective method for the quantitative determination of the quaternary ammonium antiacetylcholine-compound thiazinamium methylsulphate (Multergan) in plasma and urine is described. The procedure is based on ion pair extraction of the compound with iodide as the counter ion. This is followed by gas chromatography using an alkali flame ionization detector. The detection limit is 2 ng ml-1 with a recovery of 88-0 +/- 6-2% from plasma, 91-4 +/- 4-6% from urine. The described method can also be applied to other quaternary ammonium compounds."}
{"id": "PMID:1509", "title": "Kinetics and mechanisms of drug action on microorganisms XXII: Effects of aminosidine with and without organism pretreatment with bacteriostatic agents.", "content": "Escherichia coli generation in the logarithmic growth phase was inhibited in peptone broth USP at pH 7.0 without kill below 3.0 mug/ml of aminosidine. Above this value, the logarithms of the number of viables of the drug-treated culture ultimately decreased linearly with time and the slopes of these plots were independent of concentration. A concentration-dependent lag in the time of attainment of the cidal action was observed, and the extent of this lag was related to the ease of emergence of resistant organisms. The minimal concentration for cidal action increased with increasing concentrations of nutrients and with decreasing pH. Pretreatment of the cultures with novobiocin and tetracycline lessened the minimum bactericidal concentration of aminosidine whereas chloramphenicol pretreatment increased it. Tetracycline pretreatment inhibited the emergence of aminosidine-resistant organisms.", "contents": "Kinetics and mechanisms of drug action on microorganisms XXII: Effects of aminosidine with and without organism pretreatment with bacteriostatic agents. Escherichia coli generation in the logarithmic growth phase was inhibited in peptone broth USP at pH 7.0 without kill below 3.0 mug/ml of aminosidine. Above this value, the logarithms of the number of viables of the drug-treated culture ultimately decreased linearly with time and the slopes of these plots were independent of concentration. A concentration-dependent lag in the time of attainment of the cidal action was observed, and the extent of this lag was related to the ease of emergence of resistant organisms. The minimal concentration for cidal action increased with increasing concentrations of nutrients and with decreasing pH. Pretreatment of the cultures with novobiocin and tetracycline lessened the minimum bactericidal concentration of aminosidine whereas chloramphenicol pretreatment increased it. Tetracycline pretreatment inhibited the emergence of aminosidine-resistant organisms."}
{"id": "PMID:1510", "title": "Elementary osmotic pump.", "content": "The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal.", "contents": "Elementary osmotic pump. The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal."}
{"id": "PMID:1511", "title": "New and expedient determination of atenolol in biological samples.", "content": "A method is described for the GLC determination of atenolol BP in plasma and urine. Extraction is accomplished under dehydrating conditions, and interfering impurities are removed by using an acidified cyclohexane-isopropanol mixture (2:1) and charcoal-treated paper disks. The drug thus isolated appears to react more efficiently with heptafluorobutyric anhydride, increasing the sensitivity of GLC electron-capture analysis. Concentrations as low as 0.02 mug/ml were measured using 0.5-ml aliquots of plasma or 0.1 ml of urine. Amino alcohols such as atenolol may form hydrates or alcoholates, precluding complete derivatization with heptafluorobutyric anhydride.", "contents": "New and expedient determination of atenolol in biological samples. A method is described for the GLC determination of atenolol BP in plasma and urine. Extraction is accomplished under dehydrating conditions, and interfering impurities are removed by using an acidified cyclohexane-isopropanol mixture (2:1) and charcoal-treated paper disks. The drug thus isolated appears to react more efficiently with heptafluorobutyric anhydride, increasing the sensitivity of GLC electron-capture analysis. Concentrations as low as 0.02 mug/ml were measured using 0.5-ml aliquots of plasma or 0.1 ml of urine. Amino alcohols such as atenolol may form hydrates or alcoholates, precluding complete derivatization with heptafluorobutyric anhydride."}
{"id": "PMID:1512", "title": "Time course and dose dependence of antacid effect on urine pH.", "content": "Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing.", "contents": "Time course and dose dependence of antacid effect on urine pH. Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing."}
{"id": "PMID:1513", "title": "Quantitative analysis of tribromsalan in blood and urine.", "content": "Tribromsalan can be quantitatively measured in whole blood and urine by a technique involving extraction with ethyl acetate, treatment with silica gel, separation by TLC, and quantitative measurement by fluorescent spectrophotometry. This method has a sensitivity down to 125 ng (25 ppb in 5.0 ml of sample) of free tribromsalan and shows an average 90% recovery of tribromsalan in blood and urine with standard deviations of 9.7 and 7.4%, respectively.", "contents": "Quantitative analysis of tribromsalan in blood and urine. Tribromsalan can be quantitatively measured in whole blood and urine by a technique involving extraction with ethyl acetate, treatment with silica gel, separation by TLC, and quantitative measurement by fluorescent spectrophotometry. This method has a sensitivity down to 125 ng (25 ppb in 5.0 ml of sample) of free tribromsalan and shows an average 90% recovery of tribromsalan in blood and urine with standard deviations of 9.7 and 7.4%, respectively."}
{"id": "PMID:1514", "title": "pH-dependent secretion of procainamide into saliva.", "content": "The relationship between serum and stimulated, mixed saliva concentrations of procainamide was determined in 12 chronically medicated patients. Samples were obtained at times chosen to approximate the maximum and minimum serum concentrations of the drug during a dosing interval. Marked intersubject variability was found in the ratio of saliva to serum concentration of the drug (0.27-8.93). There was no correlation between the dose (milligrams per kilogram per day) and the minimum serum or saliva concentration of procainamide. Saliva pH ranged from 6.3 to 8.0 in eight subjects. The ratio of saliva to serum concentration of procainamide increased with decreasing pH. This result can be largely explained by the pH-dependent ionization and distribution of procainamide, a weak base.", "contents": "pH-dependent secretion of procainamide into saliva. The relationship between serum and stimulated, mixed saliva concentrations of procainamide was determined in 12 chronically medicated patients. Samples were obtained at times chosen to approximate the maximum and minimum serum concentrations of the drug during a dosing interval. Marked intersubject variability was found in the ratio of saliva to serum concentration of the drug (0.27-8.93). There was no correlation between the dose (milligrams per kilogram per day) and the minimum serum or saliva concentration of procainamide. Saliva pH ranged from 6.3 to 8.0 in eight subjects. The ratio of saliva to serum concentration of procainamide increased with decreasing pH. This result can be largely explained by the pH-dependent ionization and distribution of procainamide, a weak base."}
{"id": "PMID:1516", "title": "Sympathetic cardiovascular effects of experimental strychnine poisoning in dogs.", "content": "The cardiovascular effects of intravenously administered strychnine were studied in anesthetized and paralyzed dogs. Administration of strychnine in cumulative doses of up to 0.1 to 0.2 mg/kg caused significant pressor, as well as positive inotropic and chronotropic, effects on the heart which were abolished by adrenergic blocking agents. The cardiovascular responses possibly were elicited by a central mechanism in contrast to the peripheral inhibitory action of strychnine on the sympathetic system. Diazepam caused a marked attenuation of the pressor response with only slight changes on the heart. A combination of diazepam and propranolol would appear to be a useful therapy in cases of strychnine poisoning showing marked cardiovascular excitation.", "contents": "Sympathetic cardiovascular effects of experimental strychnine poisoning in dogs. The cardiovascular effects of intravenously administered strychnine were studied in anesthetized and paralyzed dogs. Administration of strychnine in cumulative doses of up to 0.1 to 0.2 mg/kg caused significant pressor, as well as positive inotropic and chronotropic, effects on the heart which were abolished by adrenergic blocking agents. The cardiovascular responses possibly were elicited by a central mechanism in contrast to the peripheral inhibitory action of strychnine on the sympathetic system. Diazepam caused a marked attenuation of the pressor response with only slight changes on the heart. A combination of diazepam and propranolol would appear to be a useful therapy in cases of strychnine poisoning showing marked cardiovascular excitation."}
{"id": "PMID:1517", "title": "Evaluation of the permanent sympathectomy produced by the administration of guanethidine to adult rats.", "content": "The administration of guanethidine to adult rats has been shown by morphological criteria to destroy sympathetic neurons. The objective of this study was to evaluate by biochemical and functional criteria the degree and permanence of this sympathectomy. Young adult male rats (260-300 g) were injected with saline (controls) or with guanethidine for 5 weeks. The status of the sympathetic nervous system in the animals was evaluated 1, 3 and 6 to 7 months after cessation of treatment. Seven months after cessation of treatment; the activity of tyrosine hydroxylase in the superior cervical ganglia of treated animals was greatly reduced, as were the norepinephrine levels in peripheral tissues. The concentration of epinephrine and the activity of tyrosine hydroxylase in adrenals were not different from controls at any of the times studied. Norepinephrine concentrations in several areas of the central nervous system were unchanged. Increases in blood pressure in response to stimulation of the sympathetic vasomotor outflow in the pithed rat preparation were markedly and permanently reduced in guanethidine-treated animals. Isolated intestinal nerve-muscle preparations from guanethidine-treated animals usually contracted in response to nerve stimulation, rather than relaxing as in controls. The response to stimulation of the hypogastric nerve in vas deferens preparations was reduced 1 month after cessation of treatment. The responses of the vas deferens from guanethidine-treated and control animals were the same 7 months after treatment despite a 93% reduction in norepinephrine concentration. The data demonstrate that the administration of guanethidine to adult rats produces a marked and permanent destruction of the peripheral sympathetic nervous system.", "contents": "Evaluation of the permanent sympathectomy produced by the administration of guanethidine to adult rats. The administration of guanethidine to adult rats has been shown by morphological criteria to destroy sympathetic neurons. The objective of this study was to evaluate by biochemical and functional criteria the degree and permanence of this sympathectomy. Young adult male rats (260-300 g) were injected with saline (controls) or with guanethidine for 5 weeks. The status of the sympathetic nervous system in the animals was evaluated 1, 3 and 6 to 7 months after cessation of treatment. Seven months after cessation of treatment; the activity of tyrosine hydroxylase in the superior cervical ganglia of treated animals was greatly reduced, as were the norepinephrine levels in peripheral tissues. The concentration of epinephrine and the activity of tyrosine hydroxylase in adrenals were not different from controls at any of the times studied. Norepinephrine concentrations in several areas of the central nervous system were unchanged. Increases in blood pressure in response to stimulation of the sympathetic vasomotor outflow in the pithed rat preparation were markedly and permanently reduced in guanethidine-treated animals. Isolated intestinal nerve-muscle preparations from guanethidine-treated animals usually contracted in response to nerve stimulation, rather than relaxing as in controls. The response to stimulation of the hypogastric nerve in vas deferens preparations was reduced 1 month after cessation of treatment. The responses of the vas deferens from guanethidine-treated and control animals were the same 7 months after treatment despite a 93% reduction in norepinephrine concentration. The data demonstrate that the administration of guanethidine to adult rats produces a marked and permanent destruction of the peripheral sympathetic nervous system."}
{"id": "PMID:1518", "title": "Mechanism of action of quinidine on squid axon membranes.", "content": "The mechanism of action of quinidine on squid axons has been examined by means of voltage clamp and internal perfusion techniques. When applied either externally or internally, quinidine HCl suppresses both sodium and potassium conductance increases, the effect on the former accounting for the observed decrease in action potential. The potassium conductance in quinidine undergoes a marked inactivation in a manner dependent upon the membrane potential and time, accounting for the observed prolongation of the terminal falling phase of the action potential. Quinidine methiodide exhibits the effect similar to that of quinidine HCl only when applied internally. The dissociation constants of quinidine in suppressing the sodium conducting system are estimated to be 2.4 x 10(-4) and 4.0 x 10(-4) M for quinidine HCl and methiodide, respectively. The dissociation constant of quinidine in suppressing the potassium-conducting system decreases with increasing step depolarization. When applied externally to the intact axons, quinidine HCl is more effective at external pH 8.6 than at 7.3. When perfused internally, quinidine HCl is more effective at internal pH 7.0 than at 8.0, and the potency is related to the calculated internal concentration of the charged form rather than that of the uncharged form. These results lead to the conclusion that quinidine HCl penetrates the nerve membrane in the uncharged form, is ionized in the axon and blocks the sodium and potassium conductances primarily in the charged form. Thus, quinidine and local anesthetics share some features in the terms of the site of action and active form.", "contents": "Mechanism of action of quinidine on squid axon membranes. The mechanism of action of quinidine on squid axons has been examined by means of voltage clamp and internal perfusion techniques. When applied either externally or internally, quinidine HCl suppresses both sodium and potassium conductance increases, the effect on the former accounting for the observed decrease in action potential. The potassium conductance in quinidine undergoes a marked inactivation in a manner dependent upon the membrane potential and time, accounting for the observed prolongation of the terminal falling phase of the action potential. Quinidine methiodide exhibits the effect similar to that of quinidine HCl only when applied internally. The dissociation constants of quinidine in suppressing the sodium conducting system are estimated to be 2.4 x 10(-4) and 4.0 x 10(-4) M for quinidine HCl and methiodide, respectively. The dissociation constant of quinidine in suppressing the potassium-conducting system decreases with increasing step depolarization. When applied externally to the intact axons, quinidine HCl is more effective at external pH 8.6 than at 7.3. When perfused internally, quinidine HCl is more effective at internal pH 7.0 than at 8.0, and the potency is related to the calculated internal concentration of the charged form rather than that of the uncharged form. These results lead to the conclusion that quinidine HCl penetrates the nerve membrane in the uncharged form, is ionized in the axon and blocks the sodium and potassium conductances primarily in the charged form. Thus, quinidine and local anesthetics share some features in the terms of the site of action and active form."}
{"id": "PMID:1519", "title": "Barbiturates block calcium uptake by stimulated and potassium-depolarized rat sympathetic ganglia.", "content": "The effects of two barbiturates on calcium uptake by sympathetic ganglia have been examined. Sodium pentobarbital (0.4-0.75 mM) and sodium thiopental (0.3 mM) block the preganglionic stimulation-induced uptake of 45Ca by rat superior cervical ganglia but not action potential conduction in the presynaptic axons. The ganglionic-blocking agent, tetraethylammonium, does not inhibit stimulation-induced Ca uptake and does not prevent the blocking effect of thiopental. This effect is therefore probably presynaptic. Postassium-rich media also stimulate Ca uptake by the ganglia, and this effect is markedly inhibited by pentobarbital. Since the K stimulation effect is also observed in deafferented ganglia but not in guanethidine-denervated ganglia, this effect is probably associated primarily with postsynaptic elements. In sum, the data suggest that the barbiturates inhibit Ca permeability changes in both pre- and postsynaptic neurons.", "contents": "Barbiturates block calcium uptake by stimulated and potassium-depolarized rat sympathetic ganglia. The effects of two barbiturates on calcium uptake by sympathetic ganglia have been examined. Sodium pentobarbital (0.4-0.75 mM) and sodium thiopental (0.3 mM) block the preganglionic stimulation-induced uptake of 45Ca by rat superior cervical ganglia but not action potential conduction in the presynaptic axons. The ganglionic-blocking agent, tetraethylammonium, does not inhibit stimulation-induced Ca uptake and does not prevent the blocking effect of thiopental. This effect is therefore probably presynaptic. Postassium-rich media also stimulate Ca uptake by the ganglia, and this effect is markedly inhibited by pentobarbital. Since the K stimulation effect is also observed in deafferented ganglia but not in guanethidine-denervated ganglia, this effect is probably associated primarily with postsynaptic elements. In sum, the data suggest that the barbiturates inhibit Ca permeability changes in both pre- and postsynaptic neurons."}
{"id": "PMID:1520", "title": "Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum.", "content": "1. Electrical and mechanical activities of the longtitudinal muscle of the dog antrum were recorded with the double sucrose-gap technique. 2. The muscle exhibited spontaneous action potentials which consisted of a spike-like potential which, after a brief and partial repolarization, was followed by a negative-going, plateau-type potential. In 97% of the preparations, no tension changes were produced by spontaneous action potentials. 3. Tetrodotoxin, atropine, alpha- and beta-adrenoceptor antagonists, and H1 and H2 receptor blocking agents had no effect on the action potential. It was concluded that the action potential was myogenic in origin. 4. The mean frequency of the action potential at 37+/- 0.5 degrees C was 1.0/min+/-0.06 (s.e. of mean, n=92) and the mean duration 7.1+/-0.2 sec (s.e. of mean, n=11). 5. Steady depolarizing current increased whereas hyperpolarizing current decreased the frequency of the action potential. 6. Length-tension relations were studied. In twelve strips, the average resting, passive, tension at LO was 570 mg. The active force of isometric contraction produced by acetylcholine increased with strip length up to a maximum, then decreased wtih further increased in length. There were no mechanical responses to pentagastrin. 7. Pentagastrin had two sites of action. On smooth muscle, it increased the frequency of the action potential in a dose dependent fashion. Threshold concentraions ranged from 2X10-14 to 10-11M. The ED50 was 2X10-10M. The maximum response, 5.4/min, was reached at 10-8M. Pentagastrin also released acetylcholine from intramural cholinergic nerves. 8. Pentagastrin reduced the amplitude and duration of the action potential.", "contents": "Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum. 1. Electrical and mechanical activities of the longtitudinal muscle of the dog antrum were recorded with the double sucrose-gap technique. 2. The muscle exhibited spontaneous action potentials which consisted of a spike-like potential which, after a brief and partial repolarization, was followed by a negative-going, plateau-type potential. In 97% of the preparations, no tension changes were produced by spontaneous action potentials. 3. Tetrodotoxin, atropine, alpha- and beta-adrenoceptor antagonists, and H1 and H2 receptor blocking agents had no effect on the action potential. It was concluded that the action potential was myogenic in origin. 4. The mean frequency of the action potential at 37+/- 0.5 degrees C was 1.0/min+/-0.06 (s.e. of mean, n=92) and the mean duration 7.1+/-0.2 sec (s.e. of mean, n=11). 5. Steady depolarizing current increased whereas hyperpolarizing current decreased the frequency of the action potential. 6. Length-tension relations were studied. In twelve strips, the average resting, passive, tension at LO was 570 mg. The active force of isometric contraction produced by acetylcholine increased with strip length up to a maximum, then decreased wtih further increased in length. There were no mechanical responses to pentagastrin. 7. Pentagastrin had two sites of action. On smooth muscle, it increased the frequency of the action potential in a dose dependent fashion. Threshold concentraions ranged from 2X10-14 to 10-11M. The ED50 was 2X10-10M. The maximum response, 5.4/min, was reached at 10-8M. Pentagastrin also released acetylcholine from intramural cholinergic nerves. 8. Pentagastrin reduced the amplitude and duration of the action potential."}
{"id": "PMID:1521", "title": "An alkyl etherase in rat liver.", "content": "1. Diethyl ether, which is known to be partly metabolized in vivo, has been found to show an O2 uptake with the rat liver microsomal membranes; a similar reaction is given with other short chain aliphatic ethers, isoproply and n-butyl ether. 2. The \"etherase\" reaction is optimal at pH 7.2-7.4 and is not accompanied by an increased formation of malondialdehyde. 3. When CoA is added to the microsomes together with a source of oxaloacetate and the consensing enzyme synthase, the etherase present forms citrate from diethyl ether, indicating an acetylation of CoA, which then enters the citric acid cycle. 4. Similarly to 3, fluorocitrate is formed from methyl fluoroethyl ether. 5. Differing from plasmalogens, a tetrahydropteridine does not have to be added as a co-factor.", "contents": "An alkyl etherase in rat liver. 1. Diethyl ether, which is known to be partly metabolized in vivo, has been found to show an O2 uptake with the rat liver microsomal membranes; a similar reaction is given with other short chain aliphatic ethers, isoproply and n-butyl ether. 2. The \"etherase\" reaction is optimal at pH 7.2-7.4 and is not accompanied by an increased formation of malondialdehyde. 3. When CoA is added to the microsomes together with a source of oxaloacetate and the consensing enzyme synthase, the etherase present forms citrate from diethyl ether, indicating an acetylation of CoA, which then enters the citric acid cycle. 4. Similarly to 3, fluorocitrate is formed from methyl fluoroethyl ether. 5. Differing from plasmalogens, a tetrahydropteridine does not have to be added as a co-factor."}
{"id": "PMID:1523", "title": "Micro-electrode measurement of the internal pH of crab muscle fibres.", "content": "The internal pH of crab muscle fibres was measured using recessed-tip pH-sensitive micro-electrodes. Immediately following electrode penetration the mean internal pH was 7-21 +/- 0-02 (S.E. of mean) and the mean membrane potential was -64-9 +/- 0-6 mV (S.E. of mean). If H+ ions were passively distributed across the fibre membrane the internal pH would have been 6-39. 2. The internal pH tended to rise before stabilizing at a mean value of 7-27 +/- 0-02 (S.E. of mean). The difference between immediate and stabilized values is highly significant and suggests acid injury on electrode penetration. 3. Changing the membrane potential or external pH had only small, slow effects on internal pH. 4. External CO2 caused a large and rapid decrease in internal pH. With low concentrations of CO2, the effect was dependent on the initial pH as predicted by the Law of Mass Action. During a long exposure to 2-65% CO2 at pH 7-5, the internal pH returned slowly to its previous value, suggesting active transport of H+ (or OH- or HCO3-) ions across the fibre membrane. 5. The internal buffering power calculated from the response to 2-65% CO2 was 47-3 +/- 2-8 slykes (m-equiv H+/pH unit per l.) (S.E. of mean).", "contents": "Micro-electrode measurement of the internal pH of crab muscle fibres. The internal pH of crab muscle fibres was measured using recessed-tip pH-sensitive micro-electrodes. Immediately following electrode penetration the mean internal pH was 7-21 +/- 0-02 (S.E. of mean) and the mean membrane potential was -64-9 +/- 0-6 mV (S.E. of mean). If H+ ions were passively distributed across the fibre membrane the internal pH would have been 6-39. 2. The internal pH tended to rise before stabilizing at a mean value of 7-27 +/- 0-02 (S.E. of mean). The difference between immediate and stabilized values is highly significant and suggests acid injury on electrode penetration. 3. Changing the membrane potential or external pH had only small, slow effects on internal pH. 4. External CO2 caused a large and rapid decrease in internal pH. With low concentrations of CO2, the effect was dependent on the initial pH as predicted by the Law of Mass Action. During a long exposure to 2-65% CO2 at pH 7-5, the internal pH returned slowly to its previous value, suggesting active transport of H+ (or OH- or HCO3-) ions across the fibre membrane. 5. The internal buffering power calculated from the response to 2-65% CO2 was 47-3 +/- 2-8 slykes (m-equiv H+/pH unit per l.) (S.E. of mean)."}
{"id": "PMID:1524", "title": "[Adrenergic and cholinergic control of oxytocin release evoked by vaginal, vagal and mammary stimulation in lactating rats (author's transl)].", "content": "1. The amounts of oxytocin released during Ferguson and vago-pituitary reflexes are estimated by measurements of intramammary pressure. For the milk-ejection reflex, the gain in weight of the young over a period of 30 minutes is taken as an indirect index of the release of oxytocin. 2. Antagonists of specific cholinoceptors and adrenoceptors were injected into the third ventricle in order to delineate the role of the mediators and receptors in the control of oxytocin release. 3. The results suggest that three reflexes have a specific chemical transmission since: a) The Ferguson reflex is inhibited by the drugs that only block alpha and beta adrenoceptors. b) The vago-pituitary reflex is inhibited by the drugs that block alpha and beta adrenoceptors and muscarinic cholinoceptors. c) The milk-ejection reflex is inhibited by the drugs that block alpha adrenoceptors and muscarinic and nicotinic cholinoceptors.", "contents": "[Adrenergic and cholinergic control of oxytocin release evoked by vaginal, vagal and mammary stimulation in lactating rats (author's transl)]. 1. The amounts of oxytocin released during Ferguson and vago-pituitary reflexes are estimated by measurements of intramammary pressure. For the milk-ejection reflex, the gain in weight of the young over a period of 30 minutes is taken as an indirect index of the release of oxytocin. 2. Antagonists of specific cholinoceptors and adrenoceptors were injected into the third ventricle in order to delineate the role of the mediators and receptors in the control of oxytocin release. 3. The results suggest that three reflexes have a specific chemical transmission since: a) The Ferguson reflex is inhibited by the drugs that only block alpha and beta adrenoceptors. b) The vago-pituitary reflex is inhibited by the drugs that block alpha and beta adrenoceptors and muscarinic cholinoceptors. c) The milk-ejection reflex is inhibited by the drugs that block alpha adrenoceptors and muscarinic and nicotinic cholinoceptors."}
{"id": "PMID:1525", "title": "Proteins in the luminal fluid from the bovine oviduct.", "content": "Oviducal fluid was collected by cannulation from four cows and by irrigation from fifteen slaughtered cows. The proteins in the fluid were examined by polyacrylamide gel electrophoresis at pH 4-5 and pH 8-9, isoelectric focusing on polyacrylamide, immunodiffusion, immunoelectrophoresis, affinity chromatography and gel filtration. The macromolecular components found were mainly serum proteins but small amounts of other proteins were detected in oestrous and dioestrous samples by electrophoresis at pH 8-9 following fractionation of the fluid by gel filtration or affinity chromatography. Small amounts of cathodically migrating proteins were detected directly by electrophoresis at pH 4-5 in dioestrous samples but not in oestrous samples. Determination of glycosidase activities revealed that the levels at oestrus were similar to the levels detected in serum. At dioestrus, the activities of B-N-acetylgalactosaminidase and beta-N-acetylglucosaminidase were elevated.", "contents": "Proteins in the luminal fluid from the bovine oviduct. Oviducal fluid was collected by cannulation from four cows and by irrigation from fifteen slaughtered cows. The proteins in the fluid were examined by polyacrylamide gel electrophoresis at pH 4-5 and pH 8-9, isoelectric focusing on polyacrylamide, immunodiffusion, immunoelectrophoresis, affinity chromatography and gel filtration. The macromolecular components found were mainly serum proteins but small amounts of other proteins were detected in oestrous and dioestrous samples by electrophoresis at pH 8-9 following fractionation of the fluid by gel filtration or affinity chromatography. Small amounts of cathodically migrating proteins were detected directly by electrophoresis at pH 4-5 in dioestrous samples but not in oestrous samples. Determination of glycosidase activities revealed that the levels at oestrus were similar to the levels detected in serum. At dioestrus, the activities of B-N-acetylgalactosaminidase and beta-N-acetylglucosaminidase were elevated."}
{"id": "PMID:1526", "title": "Boar seminal zinc-precipitable protein and the haemagglutinin.", "content": "About 30% of boar seminal plasma nitrogen is maximally precipitated at room temperature by 6 to 10 mM zinc in citrate solution at pH 8. A rise in the total nitrogen precipitated by 1 to 6 mM zinc is accompanied by a fall in the haemagglutinin titre of the supernatant fluid. At 6 mM zinc addition, 95% of the haemagglutinin is precipitated, but much of this is recoverable by re-solution of the zinc precipitate. Protein profile studies by gel-filtration chromatography of the zinc precipitate solution reveals a mixture of proteins, some of which are not by themselves zinc-precipitable.", "contents": "Boar seminal zinc-precipitable protein and the haemagglutinin. About 30% of boar seminal plasma nitrogen is maximally precipitated at room temperature by 6 to 10 mM zinc in citrate solution at pH 8. A rise in the total nitrogen precipitated by 1 to 6 mM zinc is accompanied by a fall in the haemagglutinin titre of the supernatant fluid. At 6 mM zinc addition, 95% of the haemagglutinin is precipitated, but much of this is recoverable by re-solution of the zinc precipitate. Protein profile studies by gel-filtration chromatography of the zinc precipitate solution reveals a mixture of proteins, some of which are not by themselves zinc-precipitable."}
{"id": "PMID:1527", "title": "Effect of season on some characteristics of stallion semen.", "content": "Season had a pronounced effect upon seminal pH and refractometer 'protein', total carbohydrate, dry weight, total N2 and lactic acid in seminal plasma of first and second ejaculates. In addition, total seminal volume, spermatozoa per ml and per ejaculate, non-protein sulphhydryl and glycerylphosphorylcholine of second ejaculates were also influenced. There was a season difference in the concentrations of lactic acid in spermatozoa from first and in total N2 from spermatozoa in second ejaculates. The effects of season on seminal plasma were greater than those on spermatozoa. Spermatozoa in first ejaculates were less affected by season than those in secons ejaculates. This differential effect on first and second ejaculates was generally true of all seminal characteristics.", "contents": "Effect of season on some characteristics of stallion semen. Season had a pronounced effect upon seminal pH and refractometer 'protein', total carbohydrate, dry weight, total N2 and lactic acid in seminal plasma of first and second ejaculates. In addition, total seminal volume, spermatozoa per ml and per ejaculate, non-protein sulphhydryl and glycerylphosphorylcholine of second ejaculates were also influenced. There was a season difference in the concentrations of lactic acid in spermatozoa from first and in total N2 from spermatozoa in second ejaculates. The effects of season on seminal plasma were greater than those on spermatozoa. Spermatozoa in first ejaculates were less affected by season than those in secons ejaculates. This differential effect on first and second ejaculates was generally true of all seminal characteristics."}
{"id": "PMID:1528", "title": "Influence of ejaculation frequency of stallions on characteristics of semen and output of spermatozoa.", "content": "Approximately 1 week was required to stabilize the extragonadal sperm reserves in stallions ejaculated daily for 10 weeks. The true daily sperm output of a stallion was equal to the mean daily sperm output of seven ejaculates +/- 1-35 X 10(9) spermatozoa. Mean concentrations of spermatozoa/ml and number of spermatozoa/ejaculate were higher (P less than 0-01) for X1 and X3/week ejaculation frequencies than for a X6/week frequency. Sperm output/week was nearly identical for a X6/week frequency. Sperm output/week was nearly identical for the X3 and X6 frequencies and higher (P less than 0-01) than the X1 frequency. Increase of ejaculation frequency from one to two ejaculates/day twice weekly significantly (P less than 0-01) raised the output of spermatozoa/week. Gel-free semen volume, spermatozoa/ml, and number of spermatozoa/ejaculate were higher (P less than 0-01) in the first, than in the second, ejaculate. Collection of semen on alternate days would be a practical ejaculation frequency for inseminating mares. Two ejaculates collected twice a week would be a practical ejaculation frequency for long-term storage of stallion semen.", "contents": "Influence of ejaculation frequency of stallions on characteristics of semen and output of spermatozoa. Approximately 1 week was required to stabilize the extragonadal sperm reserves in stallions ejaculated daily for 10 weeks. The true daily sperm output of a stallion was equal to the mean daily sperm output of seven ejaculates +/- 1-35 X 10(9) spermatozoa. Mean concentrations of spermatozoa/ml and number of spermatozoa/ejaculate were higher (P less than 0-01) for X1 and X3/week ejaculation frequencies than for a X6/week frequency. Sperm output/week was nearly identical for a X6/week frequency. Sperm output/week was nearly identical for the X3 and X6 frequencies and higher (P less than 0-01) than the X1 frequency. Increase of ejaculation frequency from one to two ejaculates/day twice weekly significantly (P less than 0-01) raised the output of spermatozoa/week. Gel-free semen volume, spermatozoa/ml, and number of spermatozoa/ejaculate were higher (P less than 0-01) in the first, than in the second, ejaculate. Collection of semen on alternate days would be a practical ejaculation frequency for inseminating mares. Two ejaculates collected twice a week would be a practical ejaculation frequency for long-term storage of stallion semen."}
{"id": "PMID:1529", "title": "Transfer of gases and metabolites in the equine placenta: a comparison with other species.", "content": "Mares and fetuses with indwelling catheters in the umbilical and uterine vessels have been used to monitor transplacental blood gas tensions, pH, O2 affinities and the concentration of various metabolites in fetal and maternal blood during late gestation. Measurements of umbilical and uterine blood flows and arterio-venous differences enabled the uptake of O2 and glucose by the fetus and the uterus to be estimated. The present findings are compared with those from other species in comparable conditions.", "contents": "Transfer of gases and metabolites in the equine placenta: a comparison with other species. Mares and fetuses with indwelling catheters in the umbilical and uterine vessels have been used to monitor transplacental blood gas tensions, pH, O2 affinities and the concentration of various metabolites in fetal and maternal blood during late gestation. Measurements of umbilical and uterine blood flows and arterio-venous differences enabled the uptake of O2 and glucose by the fetus and the uterus to be estimated. The present findings are compared with those from other species in comparable conditions."}
{"id": "PMID:1530", "title": "Androgens and oestrogens in normal and cryptorchid stallions.", "content": "Total androgens, testosterone and total oestrogens were measured in twenty-one intact, nine unilaterally cryptorchid, three bilaterally cryptorchid stallions and four geldings. Total oestrogens were significantly higher (P less than 0-005) and total androgens significantly lower (P less than 0-05) in the bilateral cryptorchid compared to other groups. There was a significant (P less than 0-025) day and night variation in total androgen levels. Thyroidectomized and intact animals showed a marked decrease in total androgen as well as testosterone levels during the winter period thus showing an effect of season on androgenic function of the testis. Disappearance rate of total and androgens following castration was extremely rapid and levels were undectable within 12 hr. Sexual stimulation appeared to increase total androgen levels. Testosterone, androstenedione, dihydrotestosterone, androstandiols, and androstenediol were identified in spermatic vein blood. Dihydrotestosterone was measured in fluid from the cauda epididymidis.", "contents": "Androgens and oestrogens in normal and cryptorchid stallions. Total androgens, testosterone and total oestrogens were measured in twenty-one intact, nine unilaterally cryptorchid, three bilaterally cryptorchid stallions and four geldings. Total oestrogens were significantly higher (P less than 0-005) and total androgens significantly lower (P less than 0-05) in the bilateral cryptorchid compared to other groups. There was a significant (P less than 0-025) day and night variation in total androgen levels. Thyroidectomized and intact animals showed a marked decrease in total androgen as well as testosterone levels during the winter period thus showing an effect of season on androgenic function of the testis. Disappearance rate of total and androgens following castration was extremely rapid and levels were undectable within 12 hr. Sexual stimulation appeared to increase total androgen levels. Testosterone, androstenedione, dihydrotestosterone, androstandiols, and androstenediol were identified in spermatic vein blood. Dihydrotestosterone was measured in fluid from the cauda epididymidis."}
{"id": "PMID:1533", "title": "Prognostic factors in polyarteritis.", "content": "The clinical course of 40 patients with polyarteritis was reviewed to determine prognostic factors and response to treatment. The first three months were the most critical to survival. Survivorship was 57 per cent at five years. Older age of onset, involvement of skeletal muscle and presence of peripheral neuropathy weighted against a satisfactory outcome. Cutaneous vasculitis was associated with a more benign course. Myocardial disease, central nervous system involvement, or hypertension were not invariably poor prognostic factors. Muscle biopsies, even in the absence of clinical involvement, were a useful diagnostic procedure, and renal angiograms were found to be a valuable alternative to renal biopsy. An unequivocal distinction on clinical and histopathologic criteria could not be made among polyarteritis nodosa, hypersentitivity angiitis, and allergic granulomatosis. Australia antigenemia occurred in six per cent of patients. Although evaluation of therapy was difficult, data from this study did not show a superiority of high vs. low dosage of corticosteroids in suppressing active disease.", "contents": "Prognostic factors in polyarteritis. The clinical course of 40 patients with polyarteritis was reviewed to determine prognostic factors and response to treatment. The first three months were the most critical to survival. Survivorship was 57 per cent at five years. Older age of onset, involvement of skeletal muscle and presence of peripheral neuropathy weighted against a satisfactory outcome. Cutaneous vasculitis was associated with a more benign course. Myocardial disease, central nervous system involvement, or hypertension were not invariably poor prognostic factors. Muscle biopsies, even in the absence of clinical involvement, were a useful diagnostic procedure, and renal angiograms were found to be a valuable alternative to renal biopsy. An unequivocal distinction on clinical and histopathologic criteria could not be made among polyarteritis nodosa, hypersentitivity angiitis, and allergic granulomatosis. Australia antigenemia occurred in six per cent of patients. Although evaluation of therapy was difficult, data from this study did not show a superiority of high vs. low dosage of corticosteroids in suppressing active disease."}
{"id": "PMID:1534", "title": "Importance of the aromatic ring in adrenergic amines. 2. Synthesis and adrenergic activity of some nonaromatic six- and eight-membered ring analogs of beta-phenylethanolamine.", "content": "The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation.", "contents": "Importance of the aromatic ring in adrenergic amines. 2. Synthesis and adrenergic activity of some nonaromatic six- and eight-membered ring analogs of beta-phenylethanolamine. The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation."}
{"id": "PMID:1535", "title": "Conformationally restricted analogs of histamine H1 receptor antagonists: trans and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine.", "content": "The syntheses of trans- and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine (1 and 2) are described. Compounds 1 and 2 were found to be inhibitors to histamine, acetylcholine, and barium chloride induced contractions of the isolated guinea pig ileum. Compounds 1 and 2 do not exhibit appreciable stereoselectivity in their ability to inhibit smooth muscle contractions. The cis compound 2 is a more effective inhibitor of histamine N-methyltransferase than the trans isomer 1.", "contents": "Conformationally restricted analogs of histamine H1 receptor antagonists: trans and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine. The syntheses of trans- and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine (1 and 2) are described. Compounds 1 and 2 were found to be inhibitors to histamine, acetylcholine, and barium chloride induced contractions of the isolated guinea pig ileum. Compounds 1 and 2 do not exhibit appreciable stereoselectivity in their ability to inhibit smooth muscle contractions. The cis compound 2 is a more effective inhibitor of histamine N-methyltransferase than the trans isomer 1."}
{"id": "PMID:1536", "title": "Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine.", "content": "Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.", "contents": "Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine. Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability."}
{"id": "PMID:1538", "title": "Prebiotic peptide-formation in the solid state. II. Reaction of glycine with adenosine 5'-triphosphate and P1,P2-diadenosine-pyrophosphate.", "content": "When a solution containing gly-N-pa and imidazole is evaporated to dryness and then maintained at a temperature between 65 degrees C and 100 degrees C, high yields of AppA and obligoglycines are obtained. We believe that ImpA is formed first, and then activates the carboxyl group of glycine or gly-A-pA. If glycine, ATP or AppA, and imidazole are heated together in the solid state, ImpA is formed and ATP , or indirectly from imidazole and gly-N-pA. Next the carboxyl group or glycine is activated by the ImpA formed in situ. The subsequent reactions of activated glycine leads to the formation of oligoglycines and the 2' (3')-glycylester of pA. Under plausible prebiobic conditions, good yields of oligoglycines up to the octamer can be obtained from glycine, ATP and imidazole.", "contents": "Prebiotic peptide-formation in the solid state. II. Reaction of glycine with adenosine 5'-triphosphate and P1,P2-diadenosine-pyrophosphate. When a solution containing gly-N-pa and imidazole is evaporated to dryness and then maintained at a temperature between 65 degrees C and 100 degrees C, high yields of AppA and obligoglycines are obtained. We believe that ImpA is formed first, and then activates the carboxyl group of glycine or gly-A-pA. If glycine, ATP or AppA, and imidazole are heated together in the solid state, ImpA is formed and ATP , or indirectly from imidazole and gly-N-pA. Next the carboxyl group or glycine is activated by the ImpA formed in situ. The subsequent reactions of activated glycine leads to the formation of oligoglycines and the 2' (3')-glycylester of pA. Under plausible prebiobic conditions, good yields of oligoglycines up to the octamer can be obtained from glycine, ATP and imidazole."}
{"id": "PMID:1539", "title": "Prebiotic peptide-formation in the solid state. III. Condensation reactions of glycine in solid state mixtures containing inorganic polyphosphates.", "content": "The reactions of glycine with inorganic polyphosphates in the solid state have been studied. The formation of peptides up to the decamer occurs at moderate temperatures(r.t.-100 degrees C) in the presence of imidazole and magnesium chloride. If adenosine 5' -monophosphate is added to the reaction mixture, 2'(3') -o-glycyl adenosine 5'-monophosphate is also obtained. These reactions could have occurred on the primitive earth.", "contents": "Prebiotic peptide-formation in the solid state. III. Condensation reactions of glycine in solid state mixtures containing inorganic polyphosphates. The reactions of glycine with inorganic polyphosphates in the solid state have been studied. The formation of peptides up to the decamer occurs at moderate temperatures(r.t.-100 degrees C) in the presence of imidazole and magnesium chloride. If adenosine 5' -monophosphate is added to the reaction mixture, 2'(3') -o-glycyl adenosine 5'-monophosphate is also obtained. These reactions could have occurred on the primitive earth."}
{"id": "PMID:1540", "title": "The prebiotic synthesis of deoxthymidine oligonucleotides. II. Comparison of condensing agents.", "content": "A reaction which oligomerizes nucleotides under possible prebiotic conditions has been characterized. Nucleoside monophosphate in the presence of cyanamide at acid pH condenses to form dithymideine pyrophosphate and phosphodiester bonded compounds. Imidazole compounds and activated precursors such as nucleoside triphosphate are not necessary for this ologomerization reaction which produces primarily cyclic ologonucleotides.", "contents": "The prebiotic synthesis of deoxthymidine oligonucleotides. II. Comparison of condensing agents. A reaction which oligomerizes nucleotides under possible prebiotic conditions has been characterized. Nucleoside monophosphate in the presence of cyanamide at acid pH condenses to form dithymideine pyrophosphate and phosphodiester bonded compounds. Imidazole compounds and activated precursors such as nucleoside triphosphate are not necessary for this ologomerization reaction which produces primarily cyclic ologonucleotides."}
{"id": "PMID:1541", "title": "Formation of nucleoside 5'-polyphosphates from nucleotides and trimetaphosphate.", "content": "When solutions of nucleoside 5'-phosphates and trimetaphosphate are dried out at room temperature, nucleoside 5'-polyphosphates are formed. The Mg++ ion shows a superior catalytic function in this reaction when compared with other divalent metal ions. Starting with nucleoside 5'-phosphates, Mg++ and trimetaphosphate, the predominant products in the nucleoside 5'-polyphosphate series pnN are p4N, P7N and p10N. Nucleoside 5'-diphosphates yield p5N and p8N, nucleoside 5'-triphosphates give p6N and p9N. The prebiological relevance of these reactions is discussed.", "contents": "Formation of nucleoside 5'-polyphosphates from nucleotides and trimetaphosphate. When solutions of nucleoside 5'-phosphates and trimetaphosphate are dried out at room temperature, nucleoside 5'-polyphosphates are formed. The Mg++ ion shows a superior catalytic function in this reaction when compared with other divalent metal ions. Starting with nucleoside 5'-phosphates, Mg++ and trimetaphosphate, the predominant products in the nucleoside 5'-polyphosphate series pnN are p4N, P7N and p10N. Nucleoside 5'-diphosphates yield p5N and p8N, nucleoside 5'-triphosphates give p6N and p9N. The prebiological relevance of these reactions is discussed."}
{"id": "PMID:1542", "title": "On the possible role of organic melanoidin polymers as matrices for prebiotic activity.", "content": "One of the major diagenetic pathways of organic matter in recent sediments involves the condensation of cellular constituents, particularly amino acids and sugars, into insoluble melanoidin-type polymers. These polymers consist mainly of humic and fulvic acids and make up the major part of the organic carbon reservoir in recent sediments. We suggest that a similar set of reactions between abiotically formed amino acids and sugars, and more generally between aldehydes and amines, occurred on a large scale in the prebiotic hydrosphere. The rapid formation of this insoluble polymeric material would have removed the bulk of the dissolved organic carbon from the primitive oceans and would thus have prevented the formation of an \"organic soup\". Melanoidin polymers have several properties which make them attractive hypothetical precursors of contemporary oxidation-reduction coenzymes: 1. they contain heterocyclic nitrogen compounds similar to the nitrogenous bases; 2. they contain a high concentration of stable free radicals; and 3. they tend to concentrate those heavy metals which play prominent roles in contemporary enzymic redox processes. The prebiotic formation of similar polymers could, therefore, have provided the starting point for a basic class of biochemical reactions. We suggest that the prebiotic scenario involved chemical and protoenzymic reactions at the sediment-ocean interface in relatively shallow waters and under conditions not much different from those of the recent environment.", "contents": "On the possible role of organic melanoidin polymers as matrices for prebiotic activity. One of the major diagenetic pathways of organic matter in recent sediments involves the condensation of cellular constituents, particularly amino acids and sugars, into insoluble melanoidin-type polymers. These polymers consist mainly of humic and fulvic acids and make up the major part of the organic carbon reservoir in recent sediments. We suggest that a similar set of reactions between abiotically formed amino acids and sugars, and more generally between aldehydes and amines, occurred on a large scale in the prebiotic hydrosphere. The rapid formation of this insoluble polymeric material would have removed the bulk of the dissolved organic carbon from the primitive oceans and would thus have prevented the formation of an \"organic soup\". Melanoidin polymers have several properties which make them attractive hypothetical precursors of contemporary oxidation-reduction coenzymes: 1. they contain heterocyclic nitrogen compounds similar to the nitrogenous bases; 2. they contain a high concentration of stable free radicals; and 3. they tend to concentrate those heavy metals which play prominent roles in contemporary enzymic redox processes. The prebiotic formation of similar polymers could, therefore, have provided the starting point for a basic class of biochemical reactions. We suggest that the prebiotic scenario involved chemical and protoenzymic reactions at the sediment-ocean interface in relatively shallow waters and under conditions not much different from those of the recent environment."}
{"id": "PMID:1543", "title": "Hemoglobin function in the vertebrates: an evolutionary model.", "content": "Comparative data on quaternary structure, cooperativity, Bohr effect and regulation by organic phosphates are reviewed for vertebrate hemoglobins. A phylogeny of hemoglobin function in the vertebrates is deduced. It is proposed that from the monomeric hemoglobin of the common ancestor of vertebrates, a deoxy dimer, as seen in the lamprey, could have originated with a single amino acid substitution. The deoxy dimer has a Bohr effect, cooperativity and a reduced oxygen affinity compared to the monomer. One, or two, additional amino acid substitutions could have resulted in the origin of a tetrameric deoxy hemoglobin which dissociated to dimers on oxygenation. Gene duplication, giving incipient alpha and beta genes, probably preceded the origin of a tetrameric oxyhemoglobin. The origin of an organic phosphate binding site on the tetrameric hemoglobin of an early fish required only one, or two, amino acid substitutions. ATP was the first organic phosphate regulator of hemoglobin function. The binding of ATP by hemoglobin may have caused the original elevation in the concentration of ATP in the red blood cells by relieving end product inhibition of ATP synthesis. The switch from regulation of hemoglobin function by ATP to regulation by DPG may have been a consequence of the curtailment of oxidative phosphorylation in the red blood cell. The basic mechanisms by which ATP and DPG concentrations can respond to strss on the oxygen transport system were present before the origin of an organic phosphate binding site on hemoglobin. A switch from ATP regulation to IP5 regulation occurred in the common ancestor of birds.", "contents": "Hemoglobin function in the vertebrates: an evolutionary model. Comparative data on quaternary structure, cooperativity, Bohr effect and regulation by organic phosphates are reviewed for vertebrate hemoglobins. A phylogeny of hemoglobin function in the vertebrates is deduced. It is proposed that from the monomeric hemoglobin of the common ancestor of vertebrates, a deoxy dimer, as seen in the lamprey, could have originated with a single amino acid substitution. The deoxy dimer has a Bohr effect, cooperativity and a reduced oxygen affinity compared to the monomer. One, or two, additional amino acid substitutions could have resulted in the origin of a tetrameric deoxy hemoglobin which dissociated to dimers on oxygenation. Gene duplication, giving incipient alpha and beta genes, probably preceded the origin of a tetrameric oxyhemoglobin. The origin of an organic phosphate binding site on the tetrameric hemoglobin of an early fish required only one, or two, amino acid substitutions. ATP was the first organic phosphate regulator of hemoglobin function. The binding of ATP by hemoglobin may have caused the original elevation in the concentration of ATP in the red blood cells by relieving end product inhibition of ATP synthesis. The switch from regulation of hemoglobin function by ATP to regulation by DPG may have been a consequence of the curtailment of oxidative phosphorylation in the red blood cell. The basic mechanisms by which ATP and DPG concentrations can respond to strss on the oxygen transport system were present before the origin of an organic phosphate binding site on hemoglobin. A switch from ATP regulation to IP5 regulation occurred in the common ancestor of birds."}
{"id": "PMID:1544", "title": "Aminoacyl transfer from an adenylate anhydride to polyribonucleotides.", "content": "Imidazole catalysis of phenylalanyl transfer from phenylalanine adenylate anhydride to the hydroxyl groups of homopolyribonucleotides was investigated as a chemical model of the biochemical aminoacylation of tRNA. Imidazole catalyzed transfer of phenylalanine to poly(U) increases from pH 6.5 to 7.7 and decreases above pH 7.7. At pH 7.7 approximately 10% of the phenylalanyl residues are transferred to poly(U). At pH 7.1, transfer to poly(U) was five times as great as to poly(A) and transfer to a poly(A) poly(U) double helix was negligible. At pH 7.1 approximately 45 mole percent linkages to poly(U) were monomeric phenylalanine; the remainder of the linkages were peptides of phenylalanine. The number of linkages and their lability to base and neutral hydroxylamine indicates that phenylalanine and its peptides are attached as esters to the 2' hydroxyl groups throughout poly(U) and the 2' (3') hydroxyl groups at the terminus of poly(U). These results do model the contemporary process of aminoacyl transfer to tRNA and continue to suggest that a histidine residue is in the active site of aminoacyl-tRNA-synthetases.", "contents": "Aminoacyl transfer from an adenylate anhydride to polyribonucleotides. Imidazole catalysis of phenylalanyl transfer from phenylalanine adenylate anhydride to the hydroxyl groups of homopolyribonucleotides was investigated as a chemical model of the biochemical aminoacylation of tRNA. Imidazole catalyzed transfer of phenylalanine to poly(U) increases from pH 6.5 to 7.7 and decreases above pH 7.7. At pH 7.7 approximately 10% of the phenylalanyl residues are transferred to poly(U). At pH 7.1, transfer to poly(U) was five times as great as to poly(A) and transfer to a poly(A) poly(U) double helix was negligible. At pH 7.1 approximately 45 mole percent linkages to poly(U) were monomeric phenylalanine; the remainder of the linkages were peptides of phenylalanine. The number of linkages and their lability to base and neutral hydroxylamine indicates that phenylalanine and its peptides are attached as esters to the 2' hydroxyl groups throughout poly(U) and the 2' (3') hydroxyl groups at the terminus of poly(U). These results do model the contemporary process of aminoacyl transfer to tRNA and continue to suggest that a histidine residue is in the active site of aminoacyl-tRNA-synthetases."}
{"id": "PMID:1545", "title": "Hybrid-versus-parental strain reaction. I. Comparative mortality in allogenetic and parental strain male and female mice.", "content": "Lethally irradiated male and female hybrids, parental strains, and the third party strain A mice were inoculated with reciprocal hybrid marrow from donors of the same sex. A graft-versus-host reaction was produced against H-Y antigens of reciprocal hybrids. Although the late mortality in inbred strain males was generally greater than that of females, without further tests this difference was not automatically attributable to an X or a Y chromosome disparity. Hybrids did not recognize the qualitative difference in antigenicity of their reciprocals, but they were able to recognize the quantitatively greater antigenicity of their parental strains, and a hybrid-versus-parental strain reaction occurred. The graft-versus-host reaction in the third party strain A mice was significantly more severe than that produced by hybrid marrow in their reciprocal hybrid recipients, but significantly less severe than that produced in the parental strains. The relationship between antigenicity and responsiveness was such that the severity of the graft-versus-host reactions masked the maternal influences observed with other reciprocal hybrids.", "contents": "Hybrid-versus-parental strain reaction. I. Comparative mortality in allogenetic and parental strain male and female mice. Lethally irradiated male and female hybrids, parental strains, and the third party strain A mice were inoculated with reciprocal hybrid marrow from donors of the same sex. A graft-versus-host reaction was produced against H-Y antigens of reciprocal hybrids. Although the late mortality in inbred strain males was generally greater than that of females, without further tests this difference was not automatically attributable to an X or a Y chromosome disparity. Hybrids did not recognize the qualitative difference in antigenicity of their reciprocals, but they were able to recognize the quantitatively greater antigenicity of their parental strains, and a hybrid-versus-parental strain reaction occurred. The graft-versus-host reaction in the third party strain A mice was significantly more severe than that produced by hybrid marrow in their reciprocal hybrid recipients, but significantly less severe than that produced in the parental strains. The relationship between antigenicity and responsiveness was such that the severity of the graft-versus-host reactions masked the maternal influences observed with other reciprocal hybrids."}
{"id": "PMID:1546", "title": "Graft versus leukemia. VI. Adoptive immunotherapy in combination with chemoradiotherapy for spontaneous leukemia-lymphoma in AKR mice.", "content": "A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To \"rescue\" the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prolongation of their median survival time and a higher 60-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice.", "contents": "Graft versus leukemia. VI. Adoptive immunotherapy in combination with chemoradiotherapy for spontaneous leukemia-lymphoma in AKR mice. A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To \"rescue\" the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prolongation of their median survival time and a higher 60-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice."}
{"id": "PMID:1547", "title": "A study of tobacco carcinogenesis. XIII. Tumor-promoting subfractions of the weakly acidic fraction.", "content": "The weakly acidic fraction (WAF) of cigarette smoke particulate matter was fractioned by silica get chromatography. We assayed the various primary subfractions for potential tumor-promoting activity by measuring the incorporation of tritiated thymidine into mouse epidermal DNA as induced by these subfractions. Based on these results and on chemical composition, the primary subfractions, were then combined into four major subfractions and tested on initiated mouse skin for tumor-promoting activity by long-term application. Two of these subfractions (40% of WAF) were inactive, whereas the other two (18 and 35% of WAF) showed tumor-promoting activity. The two active portions were then further chromatographed and tested by the short-term bioassay. Some major components of the resulting active fractions included alkyl-2-cyclopenten-2-ol-1-ones, catechols, hydroquinone, fatty acids, and 3-hydroxypyridines. Among these components, catechol, hydroquinone, 3-hydroxypyridine, 6-methyl-3-hydroxypyridine, linolenic acid, and linoleic acid were inactive as tumor promoters in the experimental animal. The activity of the alkyl-2-cyclopenten-2-ol-1-ones is unknown. Other components remain to be identified.", "contents": "A study of tobacco carcinogenesis. XIII. Tumor-promoting subfractions of the weakly acidic fraction. The weakly acidic fraction (WAF) of cigarette smoke particulate matter was fractioned by silica get chromatography. We assayed the various primary subfractions for potential tumor-promoting activity by measuring the incorporation of tritiated thymidine into mouse epidermal DNA as induced by these subfractions. Based on these results and on chemical composition, the primary subfractions, were then combined into four major subfractions and tested on initiated mouse skin for tumor-promoting activity by long-term application. Two of these subfractions (40% of WAF) were inactive, whereas the other two (18 and 35% of WAF) showed tumor-promoting activity. The two active portions were then further chromatographed and tested by the short-term bioassay. Some major components of the resulting active fractions included alkyl-2-cyclopenten-2-ol-1-ones, catechols, hydroquinone, fatty acids, and 3-hydroxypyridines. Among these components, catechol, hydroquinone, 3-hydroxypyridine, 6-methyl-3-hydroxypyridine, linolenic acid, and linoleic acid were inactive as tumor promoters in the experimental animal. The activity of the alkyl-2-cyclopenten-2-ol-1-ones is unknown. Other components remain to be identified."}
{"id": "PMID:1548", "title": "Metabolic characteristics of cells infected with a herpesvirus of turkeys.", "content": "Chicken embryo fibroblasts infected with the nononcogenic herpesvirus of turkeys (HVT) displayed an increased rate of glucose uptake, a pronounced alteration of the pH of the medium, and an increased production of lactic acid when compared to mock-infected cultures. Objective estimates of cytopathology (quantifiable neutral red uptake and cell protein determination) showed that cell deterioration was a slow process in HVT-infected cells when compared to infection by herpes simplex virus. Experiments with irradiated host cells demonstrated that HVT required functional cell DNA for replication. The inactivation of the necessary host cell function displayed multihit kinetics. In agreement  with data on other herpesviruses, HVT damaged by UV light could be photoreactivated in chick cells. The results indicate that HVT shares biologic properties in common with other herpes and transforming viruses.", "contents": "Metabolic characteristics of cells infected with a herpesvirus of turkeys. Chicken embryo fibroblasts infected with the nononcogenic herpesvirus of turkeys (HVT) displayed an increased rate of glucose uptake, a pronounced alteration of the pH of the medium, and an increased production of lactic acid when compared to mock-infected cultures. Objective estimates of cytopathology (quantifiable neutral red uptake and cell protein determination) showed that cell deterioration was a slow process in HVT-infected cells when compared to infection by herpes simplex virus. Experiments with irradiated host cells demonstrated that HVT required functional cell DNA for replication. The inactivation of the necessary host cell function displayed multihit kinetics. In agreement  with data on other herpesviruses, HVT damaged by UV light could be photoreactivated in chick cells. The results indicate that HVT shares biologic properties in common with other herpes and transforming viruses."}
{"id": "PMID:1549", "title": "Control of mercury pollution.", "content": "When a 203Ng(NO3)2 solution was kept at 25 degrees C in glass or polypropylene containers, 50 and 80% of original radioactivity was adsorbed to the containers' walls after 1 and 4 days, respectively. However, no loss in radioactivity was observed if the solution was supplemented with HgCl as carrier (100 mug Hg2+/ml) and stored in either container for 13 days. When 203Hg2+ was dissolved in glucose basal salt broth with added carrier, levels of 203Hg2+ in solution (kept in glass) decreased to 80 and 70% of original after 1 and 5 days and decreased even more if stored in polypropylene (60 and 40% of original activity after 1 and 4 days, respectively). In the absence of carrier, decreases of 203Hg2+ activities in media stored in either container were more pronounced due to chemisorption (but) not diffusion. The following factors affecting the removal of mercurials from aqueous solution stored in glass were examined: type and concentration of adsorbent (fiber glass and rubber powder); pH; pretreatment of the rubber; and the form of mercury used. Rubber was equally effective in the adsorption of organic and inorganic mercury. The pH of the aqueous 203Hg2+ solution was not a critical factor in the rate of adsorption of mercury by the rubber. In addition, the effect of soaking the rubber in water for 18 hr did not show any statistical difference when compared with nontreated rubber. It can be concluded that rubber is a very effective adsorbent of mercury and, thus, can be used as a simple method for control of mercury pollution.", "contents": "Control of mercury pollution. When a 203Ng(NO3)2 solution was kept at 25 degrees C in glass or polypropylene containers, 50 and 80% of original radioactivity was adsorbed to the containers' walls after 1 and 4 days, respectively. However, no loss in radioactivity was observed if the solution was supplemented with HgCl as carrier (100 mug Hg2+/ml) and stored in either container for 13 days. When 203Hg2+ was dissolved in glucose basal salt broth with added carrier, levels of 203Hg2+ in solution (kept in glass) decreased to 80 and 70% of original after 1 and 5 days and decreased even more if stored in polypropylene (60 and 40% of original activity after 1 and 4 days, respectively). In the absence of carrier, decreases of 203Hg2+ activities in media stored in either container were more pronounced due to chemisorption (but) not diffusion. The following factors affecting the removal of mercurials from aqueous solution stored in glass were examined: type and concentration of adsorbent (fiber glass and rubber powder); pH; pretreatment of the rubber; and the form of mercury used. Rubber was equally effective in the adsorption of organic and inorganic mercury. The pH of the aqueous 203Hg2+ solution was not a critical factor in the rate of adsorption of mercury by the rubber. In addition, the effect of soaking the rubber in water for 18 hr did not show any statistical difference when compared with nontreated rubber. It can be concluded that rubber is a very effective adsorbent of mercury and, thus, can be used as a simple method for control of mercury pollution."}
{"id": "PMID:1550", "title": "Enzymic deacetylation of carcinogenic arylacetamides by tissue microsomes of the dog and other species.", "content": "The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides.", "contents": "Enzymic deacetylation of carcinogenic arylacetamides by tissue microsomes of the dog and other species. The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides."}
{"id": "PMID:1551", "title": "Renal chromium accumulation and its relationship to chromium-induced nephrotoxicity.", "content": "This report is an attempt to study the renal handling of chromium under in vitro conditions and to relate this to the actions of the ion in the production of nephrotoxicity. Renal slice techniques were employed in these studies and were used to examine the effects of chromium on various renal transport processes. In addition, the accumulation of chromium by the renal tissue has also been studied. Marked accumulation by renal cortical slices of the rat was observed when 51Cr-labeled chromate or dichromate was added to the bathing solution. Some metabolic inhibitors interfered with this uptake process; in addition, some substrates metabolized by renal tissue reduced the accumulation of 51Cr. The use of [51Cr] dichromate and [51Cr]-chromate, as well as alterations in the bathing solution pH, indicated that in the rat chromium can interfere with renal transport processes, but that the oxidation state of this metal is not important. On the other hand, in the rabbit a greater interference with 51Cr uptake was noted at lower bathing solution pHs. This is interpreted to mean that chromate is the effective inhibitor in this species.", "contents": "Renal chromium accumulation and its relationship to chromium-induced nephrotoxicity. This report is an attempt to study the renal handling of chromium under in vitro conditions and to relate this to the actions of the ion in the production of nephrotoxicity. Renal slice techniques were employed in these studies and were used to examine the effects of chromium on various renal transport processes. In addition, the accumulation of chromium by the renal tissue has also been studied. Marked accumulation by renal cortical slices of the rat was observed when 51Cr-labeled chromate or dichromate was added to the bathing solution. Some metabolic inhibitors interfered with this uptake process; in addition, some substrates metabolized by renal tissue reduced the accumulation of 51Cr. The use of [51Cr] dichromate and [51Cr]-chromate, as well as alterations in the bathing solution pH, indicated that in the rat chromium can interfere with renal transport processes, but that the oxidation state of this metal is not important. On the other hand, in the rabbit a greater interference with 51Cr uptake was noted at lower bathing solution pHs. This is interpreted to mean that chromate is the effective inhibitor in this species."}
{"id": "PMID:1554", "title": "Sodium bicarbonate administration during cardiac arrest. Effect on arterial pH PCO2, and osmolality.", "content": "Arterial pH, Pco2, and osmolality were determined serially during cardiac resuscitation in patients and in dogs, with and without administration of sodium bicarbonate. These studies demonstrate that (1) in the absence of preexisting acidosis, severe acidosis can be prevented by adequate ventilation alone; (2) sodium bicarbonate administration results in a significant rise in arterial Pco2, which parallels the rise in pH despite adequate ventilation; (3) during prolonged cardiac and resuscitation, there is a rise in arterial osmolality that is accentuated by sodium bicarbonate. These studies suggest that sodium bicarbonate should not be used during resuscitation (1) in the absence of effective hyperventilation or where carbon dioxide removal is inadequate despite adequate ventilation, (2) in repeated doses, without confirmation of substantial acidosis, or (3) when cardiac arrest has been of brief duration and preexisting acidosis is unlikely. These studies also point to the need for a reappraisal of other buffers that do not elevate the arterial Pco2.", "contents": "Sodium bicarbonate administration during cardiac arrest. Effect on arterial pH PCO2, and osmolality. Arterial pH, Pco2, and osmolality were determined serially during cardiac resuscitation in patients and in dogs, with and without administration of sodium bicarbonate. These studies demonstrate that (1) in the absence of preexisting acidosis, severe acidosis can be prevented by adequate ventilation alone; (2) sodium bicarbonate administration results in a significant rise in arterial Pco2, which parallels the rise in pH despite adequate ventilation; (3) during prolonged cardiac and resuscitation, there is a rise in arterial osmolality that is accentuated by sodium bicarbonate. These studies suggest that sodium bicarbonate should not be used during resuscitation (1) in the absence of effective hyperventilation or where carbon dioxide removal is inadequate despite adequate ventilation, (2) in repeated doses, without confirmation of substantial acidosis, or (3) when cardiac arrest has been of brief duration and preexisting acidosis is unlikely. These studies also point to the need for a reappraisal of other buffers that do not elevate the arterial Pco2."}
{"id": "PMID:1558", "title": "Sarcotubular anomalous rectification of frog sartorius muscle.", "content": "The membrane site responsible for anomalous rectification was determined in frog sartorius muscle fibers. The total current-voltage relation of glycerol-treated fibers which represents mainly the properties of the sarcolemma was linear for membrane potentials between about -90 and -50 mV. Thus moderate depolarization-induced anomalous rectification in intact fibers represents a property of the sarcotubular system. The absence of slow hyperpolarization in glycerol-treated fibers was caused by the abolition of early conductance increase, and the sarcotubular system is responsible for the inward rectifier. Picrotoxin selectively inhibited both moderate depolarization-induced anomalous rectification and hyperpolarization-induced early conductance increase. This suggests that the same component in the sarcotubular system is responsible for these conductance changes. The inhibition with picrotoxin of moderate depolarization-induced anomalous rectification suggests the possibility that it is caused by an electrogenic effect rather than a decrease in K conductance. A sarcolemmal hyperpolarization-activated slow conductance increase was revealed.", "contents": "Sarcotubular anomalous rectification of frog sartorius muscle. The membrane site responsible for anomalous rectification was determined in frog sartorius muscle fibers. The total current-voltage relation of glycerol-treated fibers which represents mainly the properties of the sarcolemma was linear for membrane potentials between about -90 and -50 mV. Thus moderate depolarization-induced anomalous rectification in intact fibers represents a property of the sarcotubular system. The absence of slow hyperpolarization in glycerol-treated fibers was caused by the abolition of early conductance increase, and the sarcotubular system is responsible for the inward rectifier. Picrotoxin selectively inhibited both moderate depolarization-induced anomalous rectification and hyperpolarization-induced early conductance increase. This suggests that the same component in the sarcotubular system is responsible for these conductance changes. The inhibition with picrotoxin of moderate depolarization-induced anomalous rectification suggests the possibility that it is caused by an electrogenic effect rather than a decrease in K conductance. A sarcolemmal hyperpolarization-activated slow conductance increase was revealed."}
{"id": "PMID:1559", "title": "Properties of sarcolemmal delayed rectification in glycerol-treated fibers of frog sartorius muscle.", "content": "Total current-voltage relations were analyzed on nine glycerol-treated surface fibers of frog sartorius muscles in tetrodotoxin-containing isotonic normal Ringer solution. The results indicate that delayed rectification occurs in the sarcolemma on large depolarization and that delayed rectification is only partially inactivated during 1 sec of depolarization and not converted into anomalous rectification. The time to peak, the time course of inactivation and the potassium activation potential determined in glycerol-treated fibers were comparable to those analyzed previously in intact fibers. The value of the conductance increase during delayed rectification in glycerol-treated fibers appeared to be smaller than that in intact fibers.", "contents": "Properties of sarcolemmal delayed rectification in glycerol-treated fibers of frog sartorius muscle. Total current-voltage relations were analyzed on nine glycerol-treated surface fibers of frog sartorius muscles in tetrodotoxin-containing isotonic normal Ringer solution. The results indicate that delayed rectification occurs in the sarcolemma on large depolarization and that delayed rectification is only partially inactivated during 1 sec of depolarization and not converted into anomalous rectification. The time to peak, the time course of inactivation and the potassium activation potential determined in glycerol-treated fibers were comparable to those analyzed previously in intact fibers. The value of the conductance increase during delayed rectification in glycerol-treated fibers appeared to be smaller than that in intact fibers."}
{"id": "PMID:1560", "title": "Sarcolemmal slow conductance increase of frog sartorius fibers during hyperpolarization.", "content": "The properties of the hyperpolarization-activated sarcolemmal slow conductance increase in frog sartorius muscle fibers have been investigated using ethylenediaminetetraacetic acid disodium salt (EDTA) and propionate Ringer solution. More than 1 sec was required for maximum activation of the sarcolemmal slwo conductance increase. It is suggested that, although the sarcolemmal slow conductance increase was affected by deterioration, the conductance increase is not a direct product of deterioration but it represents a property of the sarcolemma which is encountered in physiological range. The sarcolemmal conductance increase was rather insensitive to the change in pH of Ringer solution. It is inferred that the absence of bellying in newly penetrated intact fibers at neutral and alkaline pHs is caused mainly by the shunting effect of large parallel conductance. Apparent augmentation with EDTA of the sarcolemmal conductance increase infers that Ca ions affect the conductance increase. The conductance increase occurred also in the EDTA-containing Cl-deficient solution. The sarcolemmal slow conductance increase has been compared with the change in Cl conductance reported by Hutter and Warner, and Warner.", "contents": "Sarcolemmal slow conductance increase of frog sartorius fibers during hyperpolarization. The properties of the hyperpolarization-activated sarcolemmal slow conductance increase in frog sartorius muscle fibers have been investigated using ethylenediaminetetraacetic acid disodium salt (EDTA) and propionate Ringer solution. More than 1 sec was required for maximum activation of the sarcolemmal slwo conductance increase. It is suggested that, although the sarcolemmal slow conductance increase was affected by deterioration, the conductance increase is not a direct product of deterioration but it represents a property of the sarcolemma which is encountered in physiological range. The sarcolemmal conductance increase was rather insensitive to the change in pH of Ringer solution. It is inferred that the absence of bellying in newly penetrated intact fibers at neutral and alkaline pHs is caused mainly by the shunting effect of large parallel conductance. Apparent augmentation with EDTA of the sarcolemmal conductance increase infers that Ca ions affect the conductance increase. The conductance increase occurred also in the EDTA-containing Cl-deficient solution. The sarcolemmal slow conductance increase has been compared with the change in Cl conductance reported by Hutter and Warner, and Warner."}
{"id": "PMID:1561", "title": "Effects of antidepressant drugs on amygdaloid after-discharge in rats.", "content": "Effects of antidepressant drugs on the amygdaloid after-discharge induced by stimulating the amygdala in rats implanted with chronic electrodes, were investigated in correlation with anti-muricidal effects as well as neurotoxicity. Tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline markedly depressed both after-discharge and muricide at doses smaller than neurotoxic doses. The effect of PF-257 was also the same as tricyclic antidepressants. On the other hand, methamphetamine and pipradrol blocked the muricide at doses smaller than neurotoxic doses without depressing the amygdaloid after-discharge. Major tranquilizers, chlorpromazine and clozapine depressed both after-discharge and muricide only at doses larger than those which impaired rotarod performance. Haloperidol, on the contrary, depressed the after-discharge without selectively blocking the muricide. Minor tranquilizers, diazepam and chlordiazepoxide did not block the muricide at doses smaller than neurotoxic doses, although they showed a marked depression of the after-discharge.", "contents": "Effects of antidepressant drugs on amygdaloid after-discharge in rats. Effects of antidepressant drugs on the amygdaloid after-discharge induced by stimulating the amygdala in rats implanted with chronic electrodes, were investigated in correlation with anti-muricidal effects as well as neurotoxicity. Tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline markedly depressed both after-discharge and muricide at doses smaller than neurotoxic doses. The effect of PF-257 was also the same as tricyclic antidepressants. On the other hand, methamphetamine and pipradrol blocked the muricide at doses smaller than neurotoxic doses without depressing the amygdaloid after-discharge. Major tranquilizers, chlorpromazine and clozapine depressed both after-discharge and muricide only at doses larger than those which impaired rotarod performance. Haloperidol, on the contrary, depressed the after-discharge without selectively blocking the muricide. Minor tranquilizers, diazepam and chlordiazepoxide did not block the muricide at doses smaller than neurotoxic doses, although they showed a marked depression of the after-discharge."}
{"id": "PMID:1562", "title": "Effects of several beta-blockers on blood pressure in the rat.", "content": "Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors.", "contents": "Effects of several beta-blockers on blood pressure in the rat. Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors."}
{"id": "PMID:1563", "title": "The clinical use of dopamine in the treatment of shock.", "content": "Dopamine is a direct-acting catecholamine with a short half-life that has many advantages in treating visceral hypoperfusion states such as shock and refractory heart failure. Unlike other inotropic drugs, dopamine directly dilates the mesenteric, renal, and cerebral vessels and redirects blood flow to essential viscera. This dopaminergic effect is prominent with doses of 100-700 mug/min in adults and is attenuated by phenothiazines and haloperidol. At doses of 700-1400 mug/min, dopamine also has a significant beta-adrenergic, inotropic effect, increasing myocardial contractility. The inotropic effect is equivalent to that of isoproterenol, epinephrine, and norepinephrine, but tachycardia, tachyarrhythmias, and angina may be less frequent with dopamine. In doses greater than 1400 mug/min, dopamine is a vasoconstrictor with pressor effects usually equivalent to that of norepinephrine. Dopamine dilates pupils, does not dilate bronchi, and does not shunt blood from viscera to skeletal muscles as does isoproterenol. Because dopamine increases myocardial contractility, selectively redistributes perfusion to essential viscera and allows a pharmacologic titration of effect, it is a logical first-choice catecholamine for treatment of shock and refractory heart failure.", "contents": "The clinical use of dopamine in the treatment of shock. Dopamine is a direct-acting catecholamine with a short half-life that has many advantages in treating visceral hypoperfusion states such as shock and refractory heart failure. Unlike other inotropic drugs, dopamine directly dilates the mesenteric, renal, and cerebral vessels and redirects blood flow to essential viscera. This dopaminergic effect is prominent with doses of 100-700 mug/min in adults and is attenuated by phenothiazines and haloperidol. At doses of 700-1400 mug/min, dopamine also has a significant beta-adrenergic, inotropic effect, increasing myocardial contractility. The inotropic effect is equivalent to that of isoproterenol, epinephrine, and norepinephrine, but tachycardia, tachyarrhythmias, and angina may be less frequent with dopamine. In doses greater than 1400 mug/min, dopamine is a vasoconstrictor with pressor effects usually equivalent to that of norepinephrine. Dopamine dilates pupils, does not dilate bronchi, and does not shunt blood from viscera to skeletal muscles as does isoproterenol. Because dopamine increases myocardial contractility, selectively redistributes perfusion to essential viscera and allows a pharmacologic titration of effect, it is a logical first-choice catecholamine for treatment of shock and refractory heart failure."}
{"id": "PMID:1567", "title": "[Certain problems of treatment of ischemic heart disease].", "content": "On the basis of extended personal experience and of the literature data, the authors give recommendations for differentiated rational drug therapy of different stages of ischaemic heart disease. The results of a study of comparative efficacy of 15 coronary-active drugs used in 709 patients with ischaemic heart disease are presented along with their clinical pharmacology, side effects, indications and counterindications. The conclusions were arrived at on the basis of an objective clinical and laboratory study of the effect of the drugs. The methods of evaluation of the drug's efficacy and of the selection of patients for the administration of adequate therapy are described, which permits to use these recommendations for practical purposes. Some problems of the pathogenesis of ischaemic heart disease are discussed in terms of the selection of pathogenetic therapy.", "contents": "[Certain problems of treatment of ischemic heart disease]. On the basis of extended personal experience and of the literature data, the authors give recommendations for differentiated rational drug therapy of different stages of ischaemic heart disease. The results of a study of comparative efficacy of 15 coronary-active drugs used in 709 patients with ischaemic heart disease are presented along with their clinical pharmacology, side effects, indications and counterindications. The conclusions were arrived at on the basis of an objective clinical and laboratory study of the effect of the drugs. The methods of evaluation of the drug's efficacy and of the selection of patients for the administration of adequate therapy are described, which permits to use these recommendations for practical purposes. Some problems of the pathogenesis of ischaemic heart disease are discussed in terms of the selection of pathogenetic therapy."}
{"id": "PMID:1568", "title": "[Stimulators of beta-adrenergic structures in treatment of ischemic heart disease].", "content": "The beneficial effect of stimulators of beta-adrenergic structures (Myophedrin on the haemodynamics and the inotropic function of the myocardium was demonstrated experimentally (in 12 rabbits) and clinically (in 53 patients with ischaemic heart disease). A positive effect of the treatment was noted in 45.5% of those patients in whom ischaemic heart disease manifested itself in angina decubitus and angina of effort.", "contents": "[Stimulators of beta-adrenergic structures in treatment of ischemic heart disease]. The beneficial effect of stimulators of beta-adrenergic structures (Myophedrin on the haemodynamics and the inotropic function of the myocardium was demonstrated experimentally (in 12 rabbits) and clinically (in 53 patients with ischaemic heart disease). A positive effect of the treatment was noted in 45.5% of those patients in whom ischaemic heart disease manifested itself in angina decubitus and angina of effort."}
{"id": "PMID:1569", "title": "[Nonachlasine--a new drug for treatment of ischemic heart disease].", "content": "Data on the pharmacology of a new antianginal drug--Nonachlasine--are presented. Nonachlasine was found to increase the blood flow intensively and for long periods of time, increasing the oxygen reserve of the myocardium, thus increasing the cardiac output and the contractile function of the heart. The prevailing action of Nonachlasine on the blood supply and the function of the myocardium seems to be the result of several mechanisms: decreasing resistance of the coronaries due to the activation of the beta2-adrenergic structures; influence upon the extravascular factors of the regulation of the coronary circulation (changes in the metabolism and cardiac activity due to the excitation of the beta-adrenergic structures). The mechanism of the positive effect of Nonachlasine upon the blood supply and function of the heart is connected with its action on the adrenergic processes. The drug accumulates noradrenaline in the myocardium and increases the activity of phosphorilase-a. This coincides in time with the increased blood supply and contractile capacity of the heart. The beta-adrenoblocking agents prevent these effects. It was postulated that the effect of Nonachlasine in the blood supply and the activity of the heart is connected with its ability to utilize the energy reserve of the myocardium by way of switching over to the anaerobic way.", "contents": "[Nonachlasine--a new drug for treatment of ischemic heart disease]. Data on the pharmacology of a new antianginal drug--Nonachlasine--are presented. Nonachlasine was found to increase the blood flow intensively and for long periods of time, increasing the oxygen reserve of the myocardium, thus increasing the cardiac output and the contractile function of the heart. The prevailing action of Nonachlasine on the blood supply and the function of the myocardium seems to be the result of several mechanisms: decreasing resistance of the coronaries due to the activation of the beta2-adrenergic structures; influence upon the extravascular factors of the regulation of the coronary circulation (changes in the metabolism and cardiac activity due to the excitation of the beta-adrenergic structures). The mechanism of the positive effect of Nonachlasine upon the blood supply and function of the heart is connected with its action on the adrenergic processes. The drug accumulates noradrenaline in the myocardium and increases the activity of phosphorilase-a. This coincides in time with the increased blood supply and contractile capacity of the heart. The beta-adrenoblocking agents prevent these effects. It was postulated that the effect of Nonachlasine in the blood supply and the activity of the heart is connected with its ability to utilize the energy reserve of the myocardium by way of switching over to the anaerobic way."}
{"id": "PMID:1570", "title": "[Cordaron and nonachlasine in treatment of chronic coronary insufficiency].", "content": "In a double blind study of the clinical effect of Cordaron conducted in 55 patients with chronic ischaemic heart disease a positive effect was obtained in 80.4% of the cases, an effect of placebo-in 24.3%. Cordaron was especially effective in patients with localized stenoses of the coronary arteries. Nonachlasine (an activator of the cardiac beta-adrenergic receptors) proved effective in 10 of 13 patients with chronic ischaemic heart disease.", "contents": "[Cordaron and nonachlasine in treatment of chronic coronary insufficiency]. In a double blind study of the clinical effect of Cordaron conducted in 55 patients with chronic ischaemic heart disease a positive effect was obtained in 80.4% of the cases, an effect of placebo-in 24.3%. Cordaron was especially effective in patients with localized stenoses of the coronary arteries. Nonachlasine (an activator of the cardiac beta-adrenergic receptors) proved effective in 10 of 13 patients with chronic ischaemic heart disease."}
{"id": "PMID:1571", "title": "[Effect of certain drugs, used in treatment of chronic coronary insufficiency, on adenosine metabolism].", "content": "It has been demonstrated that the study of the activity of 5'-nucleotidase and adenosine-desaminase permits to interpret the metabolism of adenosine. Curanthil, Sustac and Intensain influence the adenosine metabolism favouring an elevation of its content. The therapeutic effect of Obsidan is not conditioned by the \"adenosine\" metabolism.", "contents": "[Effect of certain drugs, used in treatment of chronic coronary insufficiency, on adenosine metabolism]. It has been demonstrated that the study of the activity of 5'-nucleotidase and adenosine-desaminase permits to interpret the metabolism of adenosine. Curanthil, Sustac and Intensain influence the adenosine metabolism favouring an elevation of its content. The therapeutic effect of Obsidan is not conditioned by the \"adenosine\" metabolism."}
{"id": "PMID:1572", "title": "Renal response to short-term hypocapnia in man.", "content": "This study examines the renal response to moderate hyperventilation in healthy man. Eight men hyperventilated for 26 hr (PaCO2 approximately 30 to 32 mm Hg) in normoxia (barometric pressure, PB approximately 740 mm Hg) and hypobaric hypoxia (PB approximately530 mm Hg). Anaerobic samples of arterial blood and urine were studied at two-hour intervals. Plasma [HCO3-] fell with time during sustained hypocapnia and after 26 hr was reduced 2.5 mEq/liter, with plasma pH compensated approximately 60%. Statistically significant changes in renal H+ handling were observed within the initial 2 hr of hyperventilation and were evident over the first 12 hr. Over 26 hr, mean total HCO3-excretion in hypocapnia was 10.2 mEq above control and mean total acid excretion (UVTA + UVNH4+) was 17.5 mEq below control. An increased urinary excretion of cations, especially sodium, accompanied the decrease in acid excretion. Plasma lactic acid accumulation was negligible. We conclude that renal mechanisms contribute significantly and relatively quickly to plasma pH compensation during the early phase of adaptation to hypocapnia in man.", "contents": "Renal response to short-term hypocapnia in man. This study examines the renal response to moderate hyperventilation in healthy man. Eight men hyperventilated for 26 hr (PaCO2 approximately 30 to 32 mm Hg) in normoxia (barometric pressure, PB approximately 740 mm Hg) and hypobaric hypoxia (PB approximately530 mm Hg). Anaerobic samples of arterial blood and urine were studied at two-hour intervals. Plasma [HCO3-] fell with time during sustained hypocapnia and after 26 hr was reduced 2.5 mEq/liter, with plasma pH compensated approximately 60%. Statistically significant changes in renal H+ handling were observed within the initial 2 hr of hyperventilation and were evident over the first 12 hr. Over 26 hr, mean total HCO3-excretion in hypocapnia was 10.2 mEq above control and mean total acid excretion (UVTA + UVNH4+) was 17.5 mEq below control. An increased urinary excretion of cations, especially sodium, accompanied the decrease in acid excretion. Plasma lactic acid accumulation was negligible. We conclude that renal mechanisms contribute significantly and relatively quickly to plasma pH compensation during the early phase of adaptation to hypocapnia in man."}
{"id": "PMID:1573", "title": "[The influence of isoglaucon on the hydrodynamics and haemodynamics of the eye (author's transl)].", "content": "By animal experiments and clinically we could prove that isoglaucon instillation caused the decrease in IOP due to both increase in outflow and reduction of humor secretion; the IOP decrease and changes in hydrodynamics being manifested more markedly in the fellow-eye. As reoophthalmography demonstrated \"Isoglaucon\" produced lumen narrowing in the anterior portion of the uveal tract. \"Isoglaucon\" was prescribed to 20 patients having open-angle-glaucoma, Two hours after instillation the 23 decreased in 26 eyes (of 28) by 9.3 +/- 1.0 mm Hg. When prescribed regularly \"Isoglaucon\" raised the outflow facility coefficient from 0.10 +/- 0.01 to 0.20 +/-0.02. The secretion decreased from 2.0 +/- 0.2 to 0.9 +/- 0.15. Thus, IOP decrease after \"Isoglaucon\" is accounted for by both improved outflow and reduction of aqueous humor secretion. The \"isoglucon\" instillation produced a rather moderate decrease in the total arterial pressure, though no expected parallelism in arterial and intraocular pressure was marked.", "contents": "[The influence of isoglaucon on the hydrodynamics and haemodynamics of the eye (author's transl)]. By animal experiments and clinically we could prove that isoglaucon instillation caused the decrease in IOP due to both increase in outflow and reduction of humor secretion; the IOP decrease and changes in hydrodynamics being manifested more markedly in the fellow-eye. As reoophthalmography demonstrated \"Isoglaucon\" produced lumen narrowing in the anterior portion of the uveal tract. \"Isoglaucon\" was prescribed to 20 patients having open-angle-glaucoma, Two hours after instillation the 23 decreased in 26 eyes (of 28) by 9.3 +/- 1.0 mm Hg. When prescribed regularly \"Isoglaucon\" raised the outflow facility coefficient from 0.10 +/- 0.01 to 0.20 +/-0.02. The secretion decreased from 2.0 +/- 0.2 to 0.9 +/- 0.15. Thus, IOP decrease after \"Isoglaucon\" is accounted for by both improved outflow and reduction of aqueous humor secretion. The \"isoglucon\" instillation produced a rather moderate decrease in the total arterial pressure, though no expected parallelism in arterial and intraocular pressure was marked."}
{"id": "PMID:1574", "title": "[The immediate effect of beta-isoket on the internal ocular pressure in patients with chronic simple glaucoma (author's transl)].", "content": "In 27 patients with non-compensated or medically compensated chronic simple glaucoma, the I.O.P. was measured after the administration of two tablets of beta-isoket (which contain 5 mg isosorbiddinitrate and 40 mg bupranolol). In none of the 54 eyes was the I.O.P. higher after administration of the drug. On the contrary, the I.O.P. was siginificantly or highly significantly reduced for more than 2 hours, probably because of the beta-receptor-blocking component of the preparation.", "contents": "[The immediate effect of beta-isoket on the internal ocular pressure in patients with chronic simple glaucoma (author's transl)]. In 27 patients with non-compensated or medically compensated chronic simple glaucoma, the I.O.P. was measured after the administration of two tablets of beta-isoket (which contain 5 mg isosorbiddinitrate and 40 mg bupranolol). In none of the 54 eyes was the I.O.P. higher after administration of the drug. On the contrary, the I.O.P. was siginificantly or highly significantly reduced for more than 2 hours, probably because of the beta-receptor-blocking component of the preparation."}
{"id": "PMID:1575", "title": "[Determination of IgM in serum after corneatransplantation (author's transl)].", "content": "By measuring the serum IgM-level every fourth day after keratoplasty the primary immune response can be observed. The extent of the graft's reaction corresponds with the fluctuation of IgM.", "contents": "[Determination of IgM in serum after corneatransplantation (author's transl)]. By measuring the serum IgM-level every fourth day after keratoplasty the primary immune response can be observed. The extent of the graft's reaction corresponds with the fluctuation of IgM."}
{"id": "PMID:1576", "title": "[Model of an ecological system closed as regards gas metabolism and with a periodically working autotrophic component. I. Conditions for stability of the atmospheric system].", "content": "The paper describes a semi-closed ecological system consisting of a man and a photosynthetic autotrophic component. The conditions required to maintain the stability of the atmosphere in the system are described as applied to two alternating modes of the function of the autotrophic component. These conditions express equal quantities of oxygen and carbon dioxide consumed and produced by the components of the system during any time period the length of which is the duration of the cycle of the system. On this basis equations have been derived which help to identify the photosynthetic cultures that can be used as an autotrophic component in a closed man-sustaining life support system.", "contents": "[Model of an ecological system closed as regards gas metabolism and with a periodically working autotrophic component. I. Conditions for stability of the atmospheric system]. The paper describes a semi-closed ecological system consisting of a man and a photosynthetic autotrophic component. The conditions required to maintain the stability of the atmosphere in the system are described as applied to two alternating modes of the function of the autotrophic component. These conditions express equal quantities of oxygen and carbon dioxide consumed and produced by the components of the system during any time period the length of which is the duration of the cycle of the system. On this basis equations have been derived which help to identify the photosynthetic cultures that can be used as an autotrophic component in a closed man-sustaining life support system."}
{"id": "PMID:1577", "title": "[Microbiological aspects of the performance of life support systems during prolonged operation].", "content": "The environmental control system using superoxides, sillicagels or synthetic ceolites is capable of purifying the atmosphere from microorganisms. The air conditioning system is another means for air purification from microorganisms. The possibility of microbial build-up and multiplication in the atmospheric condensate makes it necessary to assume that an air conditioning system may contribute to the transfer of conditionally pathogenic microorganisms in a space cabin. The reliability of a life support system may degrade due to an accumulation of microorganisms in its components. Further extensive studies are needed to clarify this problem.", "contents": "[Microbiological aspects of the performance of life support systems during prolonged operation]. The environmental control system using superoxides, sillicagels or synthetic ceolites is capable of purifying the atmosphere from microorganisms. The air conditioning system is another means for air purification from microorganisms. The possibility of microbial build-up and multiplication in the atmospheric condensate makes it necessary to assume that an air conditioning system may contribute to the transfer of conditionally pathogenic microorganisms in a space cabin. The reliability of a life support system may degrade due to an accumulation of microorganisms in its components. Further extensive studies are needed to clarify this problem."}
{"id": "PMID:1578", "title": "[Toxic properties of regenerated water containing methyl alcohol].", "content": "The experiments carried out on white male rats have shown no significant changes in the animals that may have resulted from their 30-day consumption of reclaimed water which contained up to 34 mg/l methanol and was produced by sorption purification of the atmospheric condensate during a prolonged manned experiment.", "contents": "[Toxic properties of regenerated water containing methyl alcohol]. The experiments carried out on white male rats have shown no significant changes in the animals that may have resulted from their 30-day consumption of reclaimed water which contained up to 34 mg/l methanol and was produced by sorption purification of the atmospheric condensate during a prolonged manned experiment."}
{"id": "PMID:1579", "title": "[Development of measures for preventing contamination of the atmosphere in hermetically sealed enclosures].", "content": "The kinetics of the outgassing of volatile substances from polymers of different function and composition was studied with respect to their natural ageing. The outgassing rate was exponentially related to the time of the sample storage. Six to nine months after the polymer fabrication the outgassing rate decreased to a minimum. Possible nobilization of synthetic materials with the aid of diffusion stabilization and thermostatization was investigated. Practical recommendations on how to prevent contamination of the enclosed atmosphere with outgassed products of synthetic materials were developed.", "contents": "[Development of measures for preventing contamination of the atmosphere in hermetically sealed enclosures]. The kinetics of the outgassing of volatile substances from polymers of different function and composition was studied with respect to their natural ageing. The outgassing rate was exponentially related to the time of the sample storage. Six to nine months after the polymer fabrication the outgassing rate decreased to a minimum. Possible nobilization of synthetic materials with the aid of diffusion stabilization and thermostatization was investigated. Practical recommendations on how to prevent contamination of the enclosed atmosphere with outgassed products of synthetic materials were developed."}
{"id": "PMID:1580", "title": "[Mathematical model of an experimental ecological system with spatially separated components].", "content": "The paper describes a model of an experimental ecological system consisting of autotrophic and heterotrophic components and a nutrient medium. The system has a zero stationary state and needs a correction. The life time of the system and the level of the necessary correction have been determined for the experimental ecological system: lettuce - slugs - nutrient solution. Optimal conditions for the conjugation of trophic components of the system have been established.", "contents": "[Mathematical model of an experimental ecological system with spatially separated components]. The paper describes a model of an experimental ecological system consisting of autotrophic and heterotrophic components and a nutrient medium. The system has a zero stationary state and needs a correction. The life time of the system and the level of the necessary correction have been determined for the experimental ecological system: lettuce - slugs - nutrient solution. Optimal conditions for the conjugation of trophic components of the system have been established."}
{"id": "PMID:1582", "title": "[Control of mineral nutrition of higher plants in biological life support systems].", "content": "Control of mineral nutrition of higher plants is one of the problems involved in the development of life support systems. The experiments on carrots cultivated aeroponically have demonstrated that mineral nutrition of plants can be controlled by means of a correction solution applied in accordance with the protocols derived from experimental studies of increase in the plant dry biomass.", "contents": "[Control of mineral nutrition of higher plants in biological life support systems]. Control of mineral nutrition of higher plants is one of the problems involved in the development of life support systems. The experiments on carrots cultivated aeroponically have demonstrated that mineral nutrition of plants can be controlled by means of a correction solution applied in accordance with the protocols derived from experimental studies of increase in the plant dry biomass."}
{"id": "PMID:1587", "title": "[Comparative evaluation of results of intertrochanteric femur osteotomy and conservative hip joint releaving treatment in Perthes-Legg-Calv\u00e9 disease].", "content": "In this paper the comparative evaluation of the results of the surgical and conservative treatment applied in patients with Perthes-Legg-Calv\u00e9 disease is given. The results obtained with intertrochanteric femur osteotomy performed in 39 patients and those obtained in 66 patients with conservative treatment are reported. The results are evaluated from the point of view of the patients' age, the localization of the process and the stages of the disease. The surgical treatment brought about in 1/3 of the cases excellent-in 1/3 good - and in 1/3 unsatisfactory results. Int the group of patients who received conservative treatment 1/3 of the cases showed excellent - 1/5 of the cases good - and 3/5 of the cases unsatisfactory results. The advantage of the surgicat treatment is that the patients are not confined to bed for long time and they must nol use walking splint releasing the hip-joint.", "contents": "[Comparative evaluation of results of intertrochanteric femur osteotomy and conservative hip joint releaving treatment in Perthes-Legg-Calv\u00e9 disease]. In this paper the comparative evaluation of the results of the surgical and conservative treatment applied in patients with Perthes-Legg-Calv\u00e9 disease is given. The results obtained with intertrochanteric femur osteotomy performed in 39 patients and those obtained in 66 patients with conservative treatment are reported. The results are evaluated from the point of view of the patients' age, the localization of the process and the stages of the disease. The surgical treatment brought about in 1/3 of the cases excellent-in 1/3 good - and in 1/3 unsatisfactory results. Int the group of patients who received conservative treatment 1/3 of the cases showed excellent - 1/5 of the cases good - and 3/5 of the cases unsatisfactory results. The advantage of the surgicat treatment is that the patients are not confined to bed for long time and they must nol use walking splint releasing the hip-joint."}
{"id": "PMID:1583", "title": "[Model of an ecosystem closed as regards gas metabolism and with a periodically working autotrophic component. II. Stability of the periodic cycles].", "content": "The literature data concerning the effect of the atmosphere composition on the photosynthetic productivity of an intensive microalgal culture were used to build a mathematical model of a semiclosed ecological system working in the light-dark alternating cycles. The type of the relationship between time cycles and composition of the stationary atmosphere of the ecological system has been established. The conditions of the existence and stability of the stationary atmosphere have been determined.", "contents": "[Model of an ecosystem closed as regards gas metabolism and with a periodically working autotrophic component. II. Stability of the periodic cycles]. The literature data concerning the effect of the atmosphere composition on the photosynthetic productivity of an intensive microalgal culture were used to build a mathematical model of a semiclosed ecological system working in the light-dark alternating cycles. The type of the relationship between time cycles and composition of the stationary atmosphere of the ecological system has been established. The conditions of the existence and stability of the stationary atmosphere have been determined."}
{"id": "PMID:1588", "title": "[Respiratory insufficiency in severely burned patients].", "content": "The increasing number of respiratory insufficiency, as well as of pulmonary complications after burns and their role in the post-traumatic mortality are pointed out by the author. The pathophysiological processes responsible for the development of post-traumatic pulmonary complications are shortly resumed. In respect of the clinical picture, three groups are distinguished by the author. One case is reported in detail. In the development of post-traumatic respiratory insufficiency important role is attributed by the author to the syndromes of micro-embolism. This supposition is supported by the laboratory examination of 10 patients. Finally the problems of prevention and therapy are discussed and the importance of the iatrogenic damages is emphasized.", "contents": "[Respiratory insufficiency in severely burned patients]. The increasing number of respiratory insufficiency, as well as of pulmonary complications after burns and their role in the post-traumatic mortality are pointed out by the author. The pathophysiological processes responsible for the development of post-traumatic pulmonary complications are shortly resumed. In respect of the clinical picture, three groups are distinguished by the author. One case is reported in detail. In the development of post-traumatic respiratory insufficiency important role is attributed by the author to the syndromes of micro-embolism. This supposition is supported by the laboratory examination of 10 patients. Finally the problems of prevention and therapy are discussed and the importance of the iatrogenic damages is emphasized."}
{"id": "PMID:1589", "title": "[Past and present management burns].", "content": "The management of burns consists essentially of the surgical removal of the necrotic skin layers and the substitution of the skin defects. Secondary skin transplantation does not prevent completely the cicatrization and all complications of the burn. The management of burns is partially classed among the problems of the conservative therapy. Early excision excludes the danger of demarcation and infection, and immediate transplantation may prevent the destruction of the subcutaneous skin layers. This advantages are assured in the cases concomitant with partial necrosis by xenotransplantation.", "contents": "[Past and present management burns]. The management of burns consists essentially of the surgical removal of the necrotic skin layers and the substitution of the skin defects. Secondary skin transplantation does not prevent completely the cicatrization and all complications of the burn. The management of burns is partially classed among the problems of the conservative therapy. Early excision excludes the danger of demarcation and infection, and immediate transplantation may prevent the destruction of the subcutaneous skin layers. This advantages are assured in the cases concomitant with partial necrosis by xenotransplantation."}
{"id": "PMID:1590", "title": "[Skin substitution in neck and facial burns].", "content": "The surgeon assuming the task of reconstruction of burned face must be skilled in plastic surgery. Primary surgical treatment and reconstruction are inseparable, therefore it is desirable that the treatment is performed since the day of the injury to the completion of the reconstruction by the same surgeon. In the surgical management of the facial burns relative conservatism is advisable. The excision is to be performed after the recovery of the second-degree burned areas. The above-mentioned principles are documented by the author on the basis of a few cases.", "contents": "[Skin substitution in neck and facial burns]. The surgeon assuming the task of reconstruction of burned face must be skilled in plastic surgery. Primary surgical treatment and reconstruction are inseparable, therefore it is desirable that the treatment is performed since the day of the injury to the completion of the reconstruction by the same surgeon. In the surgical management of the facial burns relative conservatism is advisable. The excision is to be performed after the recovery of the second-degree burned areas. The above-mentioned principles are documented by the author on the basis of a few cases."}
{"id": "PMID:1591", "title": "[Experience with the treatment of open fractures].", "content": "The number of the injuries and of the open fractures is steadily increasing. These latter are regularly due to traffic accidents. Characteristics of the open fractures are the extended lesion of the soft parts and the piece-like fractures. The treatmend depends on the patient's general state, the extension of the lesion of the soft parts, the contamination and the infection of the wound, as well as on the localization and the type of the fracture. In the case of proper indication the osteosynthesis yields satisfactory results, but it is not always to be performed and its use to exposed to dangers. The conservative treatment assures good results, if the lesion of the soft parts is minimal, the reduction of the dislocation is easily accoplished and the bone ends are to be held together. On the other hand, the method is unsuitable, if extended lesion of the soft parts occurs, as well as in the treatment of multifragmental fractures. In this group of the open fractures we must try to find other, new methods.", "contents": "[Experience with the treatment of open fractures]. The number of the injuries and of the open fractures is steadily increasing. These latter are regularly due to traffic accidents. Characteristics of the open fractures are the extended lesion of the soft parts and the piece-like fractures. The treatmend depends on the patient's general state, the extension of the lesion of the soft parts, the contamination and the infection of the wound, as well as on the localization and the type of the fracture. In the case of proper indication the osteosynthesis yields satisfactory results, but it is not always to be performed and its use to exposed to dangers. The conservative treatment assures good results, if the lesion of the soft parts is minimal, the reduction of the dislocation is easily accoplished and the bone ends are to be held together. On the other hand, the method is unsuitable, if extended lesion of the soft parts occurs, as well as in the treatment of multifragmental fractures. In this group of the open fractures we must try to find other, new methods."}
{"id": "PMID:1592", "title": "[Presence of foreign body in hand and foot, diagnosed too late].", "content": "On the basis of 7 years' material, the distribution of 73 foreign bodies - of non-metallic intensity - in the hand and the foot is discussed. The foreign bodies did not appear as new, fresh lesions, but they have been diagnosed after longer or shorter symptom-free state. In the case of fistulous process immediate removal has been performed, and in the case of closed cases - on the basis of the clinical picture - immediate removal - or removal after fixation for a few days was effective. In the author's opinion, fixation is - so long as acute symptoms are present - in all cases indispensable, - fixation is immediately followed by physicotherapy, in order to assure good functional results.", "contents": "[Presence of foreign body in hand and foot, diagnosed too late]. On the basis of 7 years' material, the distribution of 73 foreign bodies - of non-metallic intensity - in the hand and the foot is discussed. The foreign bodies did not appear as new, fresh lesions, but they have been diagnosed after longer or shorter symptom-free state. In the case of fistulous process immediate removal has been performed, and in the case of closed cases - on the basis of the clinical picture - immediate removal - or removal after fixation for a few days was effective. In the author's opinion, fixation is - so long as acute symptoms are present - in all cases indispensable, - fixation is immediately followed by physicotherapy, in order to assure good functional results."}
{"id": "PMID:1593", "title": "[Therapeutic principles and results in the management of open fractures of the tibial].", "content": "In open fractures of the leg, in which because of any reason no primary stable osteosynthesis can be performed, threading with Kirschner wire is preferred by the authors. This method assures adaptation stability, with minimal osteosynthesis. Primary closure of the wound in the soft parts is striven by the authors, - if necessary, even by plastic surgery. If primary healing of the wound is obtained and also the other conditions are favourable, the treatment after 7-10 days is the same as after covered fractures: stable osteosynthesis is performed. On the other hand, if suppuration of the wound occurs, the opposing fixed fracutre bone ends assure favourable conditions for the successful surgical treatment of the fracture. A further advantage of the method is that it may be performed without special instruments and without greater surgical experience. The results obtained with this surgical treatment of open leg fractures in the 4 years' material of the Traumatological Department of the First Surgical Clinique of the University Medical School, P\u00e9cs, are discussed by the authors.", "contents": "[Therapeutic principles and results in the management of open fractures of the tibial]. In open fractures of the leg, in which because of any reason no primary stable osteosynthesis can be performed, threading with Kirschner wire is preferred by the authors. This method assures adaptation stability, with minimal osteosynthesis. Primary closure of the wound in the soft parts is striven by the authors, - if necessary, even by plastic surgery. If primary healing of the wound is obtained and also the other conditions are favourable, the treatment after 7-10 days is the same as after covered fractures: stable osteosynthesis is performed. On the other hand, if suppuration of the wound occurs, the opposing fixed fracutre bone ends assure favourable conditions for the successful surgical treatment of the fracture. A further advantage of the method is that it may be performed without special instruments and without greater surgical experience. The results obtained with this surgical treatment of open leg fractures in the 4 years' material of the Traumatological Department of the First Surgical Clinique of the University Medical School, P\u00e9cs, are discussed by the authors."}
{"id": "PMID:1594", "title": "[Infectious complications of primary osteosynthesis in aged patients].", "content": "In respect of iatrogenic infections the elderly patients are to be considered as endangered. Modern traumatology increases this danger in consequence of the foreign materials placed in the wounds. The role of the antibiotic and chemotherapeutic prophylaxis is of utmost importance. Regrettably, the resistance of the pyogenics, especially of the strains in the hospitals is increasing, - in consequence, besides the maximal sterility the further improvement of the surgical technique and of the after-treatment are the most important tasks. In the case of infection aimed antibiotic and chemotherapeutic, resp., treatment may be successful.", "contents": "[Infectious complications of primary osteosynthesis in aged patients]. In respect of iatrogenic infections the elderly patients are to be considered as endangered. Modern traumatology increases this danger in consequence of the foreign materials placed in the wounds. The role of the antibiotic and chemotherapeutic prophylaxis is of utmost importance. Regrettably, the resistance of the pyogenics, especially of the strains in the hospitals is increasing, - in consequence, besides the maximal sterility the further improvement of the surgical technique and of the after-treatment are the most important tasks. In the case of infection aimed antibiotic and chemotherapeutic, resp., treatment may be successful."}
{"id": "PMID:1595", "title": "[Soft tissue complications and their reconstruction following osteosynthesis of open tibial fractures].", "content": "The nowadays accepted principles of the treament of open leg fractures are discussed. The open character of the lesion multiplies the possibilities of complications. In the present paper the complications of the bone recovery are not dealt with, only the complications observed in the soft parts and the possibilities of their treatment are analysed by the authors. According to the severity of the soft parts complications free transplantation of semi-thick skin, pedicle flap plasty, double-end graft plasty, crossed flap grafting, as well as the primary and secondary variations of these methods are used by the authors. The satisfactory results obtained with these methods even in spite of the complications are pointed out by the authors.", "contents": "[Soft tissue complications and their reconstruction following osteosynthesis of open tibial fractures]. The nowadays accepted principles of the treament of open leg fractures are discussed. The open character of the lesion multiplies the possibilities of complications. In the present paper the complications of the bone recovery are not dealt with, only the complications observed in the soft parts and the possibilities of their treatment are analysed by the authors. According to the severity of the soft parts complications free transplantation of semi-thick skin, pedicle flap plasty, double-end graft plasty, crossed flap grafting, as well as the primary and secondary variations of these methods are used by the authors. The satisfactory results obtained with these methods even in spite of the complications are pointed out by the authors."}
{"id": "PMID:1596", "title": "[Experience with the treatment of open leg fractures].", "content": "Open leg fractures observed in 81 patients are analysed by the authors. In case of conservative treatment alone and in the group, which has been treated with primary osteosynthesis satisfactory results have been observed by the authors. False joint and osteomyelitis happened only in the group, in which the patients obtained firstly conservative treatment and in the case of the failure of this treatment osteosynthesis has been carried out. In the authors' opinion the most frequent complications are due - besides the damage of the soft parts - to the repeated and sometimes erroneous interventions.", "contents": "[Experience with the treatment of open leg fractures]. Open leg fractures observed in 81 patients are analysed by the authors. In case of conservative treatment alone and in the group, which has been treated with primary osteosynthesis satisfactory results have been observed by the authors. False joint and osteomyelitis happened only in the group, in which the patients obtained firstly conservative treatment and in the case of the failure of this treatment osteosynthesis has been carried out. In the authors' opinion the most frequent complications are due - besides the damage of the soft parts - to the repeated and sometimes erroneous interventions."}
{"id": "PMID:1599", "title": "[Primary humero-radial arthrodesis].", "content": "The surgical treatment of a severe injury in the cubital region of a bus-driver, aged 47, is reported. Because of the extended contamination and the splintered fracture radical wound excision - involving also the chondral surfaces - has been performed and hereupon humero-radial arthrodesis was carried out. The skin defect has been successfully treated secondarily by insert of a flap. After uneventful recovery the patient could resume his work 6 months after the injury again.", "contents": "[Primary humero-radial arthrodesis]. The surgical treatment of a severe injury in the cubital region of a bus-driver, aged 47, is reported. Because of the extended contamination and the splintered fracture radical wound excision - involving also the chondral surfaces - has been performed and hereupon humero-radial arthrodesis was carried out. The skin defect has been successfully treated secondarily by insert of a flap. After uneventful recovery the patient could resume his work 6 months after the injury again."}
{"id": "PMID:1600", "title": "[Xenograft in the treatment of burns].", "content": "The injury due to burns embraces three, nearly concentric zones. The necrobiosis of the central and marginal zones is reversible and the pig-skin - assuring biological ligature - plays important role in turning for better of the process. The preparation and use of Xenograft - applied in the author's department - is discussed.", "contents": "[Xenograft in the treatment of burns]. The injury due to burns embraces three, nearly concentric zones. The necrobiosis of the central and marginal zones is reversible and the pig-skin - assuring biological ligature - plays important role in turning for better of the process. The preparation and use of Xenograft - applied in the author's department - is discussed."}
{"id": "PMID:1602", "title": "Mosquito-borne arboviruses in arctic america.", "content": "Mosquito-borne arboviruses are prevalent throughout subarctic regions of Canada and Alaska, principally in the boreal forest extending between latitudes 53 and 66 degrees N, but they have been identified in tundra regions as far north as 70 degrees N. All mosquito-borne agents have been bunyaviruses, comprising principally the snowshoe hare subtype of California encephalitis (CE) virus, but also Northway virus. Mosquito vectors comprise several Aedes species and Culiseta inornata, all of which have supported replication of CE virus following incubation at 13 degrees C or lower temperatures. Isolation of virus from wild-caught larvae points towards transovarial transfer. Principal vertebrate reservoirs of infection are mammals, especially snowshoe hares (Lepus americanus) and ground squirrels (Citellus undulatus). Where the boreal forest merges into prairie grassland around 53 degrees N, Culex tarsalis mosquitoes become prevalent, and an alphavirus, western equine encephalomyelitis, is detected more frequently than CE virus.", "contents": "Mosquito-borne arboviruses in arctic america. Mosquito-borne arboviruses are prevalent throughout subarctic regions of Canada and Alaska, principally in the boreal forest extending between latitudes 53 and 66 degrees N, but they have been identified in tundra regions as far north as 70 degrees N. All mosquito-borne agents have been bunyaviruses, comprising principally the snowshoe hare subtype of California encephalitis (CE) virus, but also Northway virus. Mosquito vectors comprise several Aedes species and Culiseta inornata, all of which have supported replication of CE virus following incubation at 13 degrees C or lower temperatures. Isolation of virus from wild-caught larvae points towards transovarial transfer. Principal vertebrate reservoirs of infection are mammals, especially snowshoe hares (Lepus americanus) and ground squirrels (Citellus undulatus). Where the boreal forest merges into prairie grassland around 53 degrees N, Culex tarsalis mosquitoes become prevalent, and an alphavirus, western equine encephalomyelitis, is detected more frequently than CE virus."}
{"id": "PMID:1604", "title": "The significance of mosquito longevity and blood-feeding behaviour in the dynamics of arbovirus infections.", "content": "Mosquito longevity and blood-feeding behaviour are very important but neglected factors in the dynamics of arbovirus infections as changes in them affect transmission rates exponentially. Some mosquito species feed on a narrow range of vertebrates, some on a wide range, both influenced by host-availability and other environmental and behavioural factors. Only those which feed on maintenance hosts contribute to maintenance of the infection. Some species change their feeding pattern with season. The frequency of blood-feeding depends inter alia on environmental temperature. Longevity is perhaps most important: the majority of mosquitoes infected probably do not survive long enough to become infective; it is influenced by relative humidity, temperature and predation. Longevity, feeding frequency and the extrinsic incubation period are all temperature dependent and are therefore important rate determinants in seasonal epizootics or epidemics. Equally, their relative stability in the tropics contributes to the equilibrium of an enzootic or endemic.", "contents": "The significance of mosquito longevity and blood-feeding behaviour in the dynamics of arbovirus infections. Mosquito longevity and blood-feeding behaviour are very important but neglected factors in the dynamics of arbovirus infections as changes in them affect transmission rates exponentially. Some mosquito species feed on a narrow range of vertebrates, some on a wide range, both influenced by host-availability and other environmental and behavioural factors. Only those which feed on maintenance hosts contribute to maintenance of the infection. Some species change their feeding pattern with season. The frequency of blood-feeding depends inter alia on environmental temperature. Longevity is perhaps most important: the majority of mosquitoes infected probably do not survive long enough to become infective; it is influenced by relative humidity, temperature and predation. Longevity, feeding frequency and the extrinsic incubation period are all temperature dependent and are therefore important rate determinants in seasonal epizootics or epidemics. Equally, their relative stability in the tropics contributes to the equilibrium of an enzootic or endemic."}
{"id": "PMID:1605", "title": "Properties of Semliki Forest virus nucleocapsid.", "content": "The nucleocapsid of the Semliki Forest virus is composed of 34% RNA and 66% protein, or one RNA and about 240 capsid protein molecules. The particle is spherical, with a diameter of 38--39 nm. If the nucleocapsid is exposed to slightly acid pH (6.4--5.6) it undergoes a structural change and is contracted to a 32 nm state. A similar contraction can be effected by RNase treatment, in this case, however, in connection with a loss of RNA. Treatment of the nucleocapsid with 0.2 mM SDS results in dissociation of capsid protein from RNA, an effect which suggests strong RNA-protein interaction. At 0.05 mM SDS the protein remains associated with the RNA, but the S-value is reduced from 150 S to 100 S. Electron micrographs of the 100 S ribonucleoprotein showed irregular and strand-like structures.", "contents": "Properties of Semliki Forest virus nucleocapsid. The nucleocapsid of the Semliki Forest virus is composed of 34% RNA and 66% protein, or one RNA and about 240 capsid protein molecules. The particle is spherical, with a diameter of 38--39 nm. If the nucleocapsid is exposed to slightly acid pH (6.4--5.6) it undergoes a structural change and is contracted to a 32 nm state. A similar contraction can be effected by RNase treatment, in this case, however, in connection with a loss of RNA. Treatment of the nucleocapsid with 0.2 mM SDS results in dissociation of capsid protein from RNA, an effect which suggests strong RNA-protein interaction. At 0.05 mM SDS the protein remains associated with the RNA, but the S-value is reduced from 150 S to 100 S. Electron micrographs of the 100 S ribonucleoprotein showed irregular and strand-like structures."}
{"id": "PMID:1608", "title": "[Demonstration of T-cell activation using synthetic polynucleotides].", "content": "The present data show that SPN have a striking influence on thymus dependent T cells. The enhancing effect of gvh reactions on antibody formation against thymus dependent antigens give a good explanation for the antitumor effects of this substance.", "contents": "[Demonstration of T-cell activation using synthetic polynucleotides]. The present data show that SPN have a striking influence on thymus dependent T cells. The enhancing effect of gvh reactions on antibody formation against thymus dependent antigens give a good explanation for the antitumor effects of this substance."}
{"id": "PMID:1609", "title": "[Stress incontinence in the woman (author's transl)].", "content": "The morphology and function of the urethrovesical junction are described to give some understanding of the pathogenesis and therapy of female stress incontinence. Conservative procedures can only be helpful in stage-1 stress incontinence, whereas in stage 2 surgical treatment provides excellent results.", "contents": "[Stress incontinence in the woman (author's transl)]. The morphology and function of the urethrovesical junction are described to give some understanding of the pathogenesis and therapy of female stress incontinence. Conservative procedures can only be helpful in stage-1 stress incontinence, whereas in stage 2 surgical treatment provides excellent results."}
{"id": "PMID:1620", "title": "Regulatory function of pyruvate dehydrogenase and the mitochondrion in lipogenesis.", "content": "The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower \"energy pressure\" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process.", "contents": "Regulatory function of pyruvate dehydrogenase and the mitochondrion in lipogenesis. The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower \"energy pressure\" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process."}
{"id": "PMID:1621", "title": "Studies in vitro of lipogenesis in rat testicular tissue.", "content": "Testicular tissue was shown to contain the full complement of enzymes required for de novo synthesis of fatty acids. The enzymes capable of snythesizing palmitic acid from citrate, acetate, or acetyl CoA were found to be present in the soluble (cytoplasmic) fraction. These included fatty acid synthetase, acetyl CoA carboxylase, citrate-cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Optimal conditions for assaying activities of fatty acid synthetase and acetyl CoA carboxylase in the soluble fraction from rat testes were established, and the activities of these two enzymes were determined to be 0.54 +/- 0.1 and 0.030 +/- 0.002 (nmoles of substrate incorporated into fatty acid per min per mg of soluble fraction protein), respectively. The activities of citrate-cleavage enzyme, malic enzyme, and the glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase pair were also measured. The activities were 6.0 +/- 0.7, 34.9 +/- 4.2, and 29.9 +/- 9.3 nmoles/min/mg, respectively.", "contents": "Studies in vitro of lipogenesis in rat testicular tissue. Testicular tissue was shown to contain the full complement of enzymes required for de novo synthesis of fatty acids. The enzymes capable of snythesizing palmitic acid from citrate, acetate, or acetyl CoA were found to be present in the soluble (cytoplasmic) fraction. These included fatty acid synthetase, acetyl CoA carboxylase, citrate-cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Optimal conditions for assaying activities of fatty acid synthetase and acetyl CoA carboxylase in the soluble fraction from rat testes were established, and the activities of these two enzymes were determined to be 0.54 +/- 0.1 and 0.030 +/- 0.002 (nmoles of substrate incorporated into fatty acid per min per mg of soluble fraction protein), respectively. The activities of citrate-cleavage enzyme, malic enzyme, and the glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase pair were also measured. The activities were 6.0 +/- 0.7, 34.9 +/- 4.2, and 29.9 +/- 9.3 nmoles/min/mg, respectively."}
{"id": "PMID:1622", "title": "Fatty acid synthesis from 2-14C-acetate in rat testis mitochondrial and cytosol fractions in vitro.", "content": "An in vitro system for acetate incorporation into fatty acids by the mitochondrial and the cytosol fractions of rat testis is described. The rate of incorporation of acetate into fatty acids was twice as fast with the mitochondrial as with the cytosol fraction; both systems were stimulated in the presence of adenosine triphosphate, reduced nicotinamide adenine dinucleotide phosphate, coenzyme A, and MgC1(2). The optimum pH was between 7.0-7.5 for the mitochondrial fraction and between 6.5-8.0 for the cytosol fraction. Radio gas chromatography showed that palmitic acid was the most highly labeled acid, followed by stearic acid, in the mitochondrial fraction in accord with the pathway of de novo fatty acid synthesis. Some of the labeled acetate was also incorporated into the 16:1 and 18:1 fatty acids of this fraction. Distribution of radioactivity among the mitochondrial lipid classes was highest in the phospholipids and monoglycerides, followed by diglycerides and cholesterol; little radioactivity was present in the triglyceride fraction. These observations are in accord with studies of the incorporation of labeled metabolites into testicular lipids following intratesticular injection and indicate the validity of the in vitro system for studies of specific reactions occurring in vivo.", "contents": "Fatty acid synthesis from 2-14C-acetate in rat testis mitochondrial and cytosol fractions in vitro. An in vitro system for acetate incorporation into fatty acids by the mitochondrial and the cytosol fractions of rat testis is described. The rate of incorporation of acetate into fatty acids was twice as fast with the mitochondrial as with the cytosol fraction; both systems were stimulated in the presence of adenosine triphosphate, reduced nicotinamide adenine dinucleotide phosphate, coenzyme A, and MgC1(2). The optimum pH was between 7.0-7.5 for the mitochondrial fraction and between 6.5-8.0 for the cytosol fraction. Radio gas chromatography showed that palmitic acid was the most highly labeled acid, followed by stearic acid, in the mitochondrial fraction in accord with the pathway of de novo fatty acid synthesis. Some of the labeled acetate was also incorporated into the 16:1 and 18:1 fatty acids of this fraction. Distribution of radioactivity among the mitochondrial lipid classes was highest in the phospholipids and monoglycerides, followed by diglycerides and cholesterol; little radioactivity was present in the triglyceride fraction. These observations are in accord with studies of the incorporation of labeled metabolites into testicular lipids following intratesticular injection and indicate the validity of the in vitro system for studies of specific reactions occurring in vivo."}
{"id": "PMID:1623", "title": "Fat metabolism in higher plants: metabolism of medium chain fatty acids.", "content": "Cell free preparations of avocado mesocarp and spinach leaf tissue rapidly convert lauryl CoA to DL-3-hydroxyl lauric acid as well as 2-, and 3-dodecanoic acids. The conversion does not occur under anaerobic conditions unless a suitable redox carrier such as ferredoxin is present. H2 18O is incorporated into the 3-hydroxyl function, but O2(18) is not. The characteristics of this system are presented and a possible function of this system is proposed.", "contents": "Fat metabolism in higher plants: metabolism of medium chain fatty acids. Cell free preparations of avocado mesocarp and spinach leaf tissue rapidly convert lauryl CoA to DL-3-hydroxyl lauric acid as well as 2-, and 3-dodecanoic acids. The conversion does not occur under anaerobic conditions unless a suitable redox carrier such as ferredoxin is present. H2 18O is incorporated into the 3-hydroxyl function, but O2(18) is not. The characteristics of this system are presented and a possible function of this system is proposed."}
{"id": "PMID:1624", "title": "Stearoyl-CoA desaturase activity in mammary adenocarcinomas carried by C3H mice.", "content": "Transplantable mammary adenocarcinomas and livers of C3H mice fed a stock diet or a linoleate rich diet (15% corn oil) contain similar amounts of oleate (ca 3 mg/gm tissue). On feeding either a high carbohydrate, fat free or a high carbohydrate, saturated fat-containing (15% hydrogenated coconut or cottonseed oil) diet for 6 weeks, oleate levels increased 2-fold in tumor and 5-fold in liver. The specific activity of stearoyl-CoA desaturase in liver microsomes was similar to that in the corresponding fractions of mammary glands of lactating mice. In liver, this activity was enhanced 2- to 3-fold by feeding a high carbohydrate, fat free or a high carbohydrate, saturated fat diet. The desaturase activity in mammary tumor microsomes, while only 10% of that in hepatic microsomes, remained unaltered regardless of the type of diet fed. These observations suggest that (a) a major portion of the oleate in the mammary tumor is not produced within the tissue, (b) dietary adaptation is not a general characteristic of stearoyl-CoA desaturase in neoplastic tissues, and (c) enhanced desaturase activity in liver is directly related to the absence of linoleate or oleate, or to a large decrease in oleate in the diet.", "contents": "Stearoyl-CoA desaturase activity in mammary adenocarcinomas carried by C3H mice. Transplantable mammary adenocarcinomas and livers of C3H mice fed a stock diet or a linoleate rich diet (15% corn oil) contain similar amounts of oleate (ca 3 mg/gm tissue). On feeding either a high carbohydrate, fat free or a high carbohydrate, saturated fat-containing (15% hydrogenated coconut or cottonseed oil) diet for 6 weeks, oleate levels increased 2-fold in tumor and 5-fold in liver. The specific activity of stearoyl-CoA desaturase in liver microsomes was similar to that in the corresponding fractions of mammary glands of lactating mice. In liver, this activity was enhanced 2- to 3-fold by feeding a high carbohydrate, fat free or a high carbohydrate, saturated fat diet. The desaturase activity in mammary tumor microsomes, while only 10% of that in hepatic microsomes, remained unaltered regardless of the type of diet fed. These observations suggest that (a) a major portion of the oleate in the mammary tumor is not produced within the tissue, (b) dietary adaptation is not a general characteristic of stearoyl-CoA desaturase in neoplastic tissues, and (c) enhanced desaturase activity in liver is directly related to the absence of linoleate or oleate, or to a large decrease in oleate in the diet."}
{"id": "PMID:1625", "title": "Iowa wrestling study: changes in the urinary profiles of wrestlers prior to and after competition.", "content": "During the 1973 and 1974 state high school wrestling championships, urine samples were obtained from wrestlers prior to the weigh-in, immediately before they wrestled, and immediately after the subjects had completed their match. Specific gravity, osmolarity, pH, sodium and potassium determinations, as well as qualitative tests for protein and ketones, indicated that the wrestlers were in a dehydrated state at the time of weigh-in. After the five hour interim between the weigh-in and the first match, all but the pH measure remained essentially unchanged. This absence of significant changes in the urinary profile suggests that the wrestlers were unable to rehydrate during the five hour time period between the weigh-in and the first match and that they were competing in a dehydrated state. Urine samples collected after competition were significantly lower in specific gravity, osmolarity and potassium concentration than samples obtained before the match. The urinary potassium levels were of interest because at the three conditions (weigh-in, before the first match, after competition) they were 73-182% higher than values reported for high school students who were nonwrestlers.", "contents": "Iowa wrestling study: changes in the urinary profiles of wrestlers prior to and after competition. During the 1973 and 1974 state high school wrestling championships, urine samples were obtained from wrestlers prior to the weigh-in, immediately before they wrestled, and immediately after the subjects had completed their match. Specific gravity, osmolarity, pH, sodium and potassium determinations, as well as qualitative tests for protein and ketones, indicated that the wrestlers were in a dehydrated state at the time of weigh-in. After the five hour interim between the weigh-in and the first match, all but the pH measure remained essentially unchanged. This absence of significant changes in the urinary profile suggests that the wrestlers were unable to rehydrate during the five hour time period between the weigh-in and the first match and that they were competing in a dehydrated state. Urine samples collected after competition were significantly lower in specific gravity, osmolarity and potassium concentration than samples obtained before the match. The urinary potassium levels were of interest because at the three conditions (weigh-in, before the first match, after competition) they were 73-182% higher than values reported for high school students who were nonwrestlers."}
{"id": "PMID:1628", "title": "Vasculitis with hepatitis B antigenemia: long-term observation in nine patients.", "content": "The development of generalized necrotizing vasculitis in association with hepatitis B antigenemia is the first example in man of a chronic rheumatic disease presumably caused by a viral infection. This report reviews the experience in nine biopsy-proven cases of hepatitis B-associated necrotizing vasculitis followed for up to six years. The natural history of the disease is emphasized and the manifestations of patients with vasculitis who carry hepatitis B antigen are compared with those of vasculitis patients who are antigen negative.", "contents": "Vasculitis with hepatitis B antigenemia: long-term observation in nine patients. The development of generalized necrotizing vasculitis in association with hepatitis B antigenemia is the first example in man of a chronic rheumatic disease presumably caused by a viral infection. This report reviews the experience in nine biopsy-proven cases of hepatitis B-associated necrotizing vasculitis followed for up to six years. The natural history of the disease is emphasized and the manifestations of patients with vasculitis who carry hepatitis B antigen are compared with those of vasculitis patients who are antigen negative."}
{"id": "PMID:1629", "title": "Polyarthritis, polyarteritis and hepatitis B.", "content": "An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide.", "contents": "Polyarthritis, polyarteritis and hepatitis B. An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide."}
{"id": "PMID:1630", "title": "Some evidence for aldosterone action on 2,3-diphosphoglycerate level in human red cells.", "content": "In healthy male subjects aldosterone excretion and plasma renin activity were reduced by a 4-6 hr head-out immersion in thermoindifferent water baths (35.5 +/- 0.1 degrees C). The red cell 2,3-diphosphoglycerate (DPG) concentration before and throughout immersion period was positively correlated both with aldosterone excretion in 2 hr pooled urine (r = +0.69; 2 p less than 0.001) and with renin activity (r = + 0.54; 2p less than 0.001) despite a concomitant increase of cubital venous pH and inorganic phosphate concentration. These findings furnish evidence for a regulatory role of aldosterone in DPG metabolism, possibily by a direct influence on red cell glycolysis.", "contents": "Some evidence for aldosterone action on 2,3-diphosphoglycerate level in human red cells. In healthy male subjects aldosterone excretion and plasma renin activity were reduced by a 4-6 hr head-out immersion in thermoindifferent water baths (35.5 +/- 0.1 degrees C). The red cell 2,3-diphosphoglycerate (DPG) concentration before and throughout immersion period was positively correlated both with aldosterone excretion in 2 hr pooled urine (r = +0.69; 2 p less than 0.001) and with renin activity (r = + 0.54; 2p less than 0.001) despite a concomitant increase of cubital venous pH and inorganic phosphate concentration. These findings furnish evidence for a regulatory role of aldosterone in DPG metabolism, possibily by a direct influence on red cell glycolysis."}
{"id": "PMID:1631", "title": "[Alcohol dehydrogenase activity of nonsulfur purple bacteria].", "content": "Rhodopseudomonas palustris, Rh. viridis, Rh. acidophila, and Rhodomicrobium vanniellii grow on media containing ethanol, n-propanol, and n-butanol. The highest amount of lower alcohols is utilized by the strains of Rh. palustris. Only Rh. acidophila accumulates methanol. Alcohol dehydrogenase of Rh. palustris, Rh. viridis, and Rhodospirillum rubrum requires for its activity NAD, that of Rhodomicrobium vanniellii--NADP, and the enzyme of Rh. acidophila is active in the presence of phenazine metasulphate (PMS) and ammonium ions. Aldehyde dehydrogenase from two strains of Rh. palustris also requires NAD; the Nakamura strain is active in the presence of PMS. Aldehyde dehydrogenase of Rh. acidophila is active in the presence of PMS and ammonium ions. Different bacterial species vary in the substrate specificity of their alcohol dehydrogenases.", "contents": "[Alcohol dehydrogenase activity of nonsulfur purple bacteria]. Rhodopseudomonas palustris, Rh. viridis, Rh. acidophila, and Rhodomicrobium vanniellii grow on media containing ethanol, n-propanol, and n-butanol. The highest amount of lower alcohols is utilized by the strains of Rh. palustris. Only Rh. acidophila accumulates methanol. Alcohol dehydrogenase of Rh. palustris, Rh. viridis, and Rhodospirillum rubrum requires for its activity NAD, that of Rhodomicrobium vanniellii--NADP, and the enzyme of Rh. acidophila is active in the presence of phenazine metasulphate (PMS) and ammonium ions. Aldehyde dehydrogenase from two strains of Rh. palustris also requires NAD; the Nakamura strain is active in the presence of PMS. Aldehyde dehydrogenase of Rh. acidophila is active in the presence of PMS and ammonium ions. Different bacterial species vary in the substrate specificity of their alcohol dehydrogenases."}
{"id": "PMID:1632", "title": "[Development of Mycobacterium lacticolum and its synthesis of exopolysaccharide under conditions of varying acidity of the medium].", "content": "Mycobacterium lacticolum 121 grows and synthesizes exopolysaccharide at the initial values of pH of the medium from 5.0 to 11.5. The accumulation of biomass is maximal (10 to 12 gram/litre) at pH 6.0 to 11.5; the rate of growth is highest at pH 8.0 to 11.5. The largest amount of exopolysaccharide (2.0 to 2.4 gram/litre) is produced in the medium at pH 8.0 to 11.0; the rate of its production is highest at pH 9.0 to 11.0. The growth of Mycobacterium lacticolum 121 and the biosynthesis of polysaccharide are optimal at pH 8.0 to 8.2. Changes in acidity of the medium have no effect on the qualitative composition, structure, and molecular weight of the polysaccharide.", "contents": "[Development of Mycobacterium lacticolum and its synthesis of exopolysaccharide under conditions of varying acidity of the medium]. Mycobacterium lacticolum 121 grows and synthesizes exopolysaccharide at the initial values of pH of the medium from 5.0 to 11.5. The accumulation of biomass is maximal (10 to 12 gram/litre) at pH 6.0 to 11.5; the rate of growth is highest at pH 8.0 to 11.5. The largest amount of exopolysaccharide (2.0 to 2.4 gram/litre) is produced in the medium at pH 8.0 to 11.0; the rate of its production is highest at pH 9.0 to 11.0. The growth of Mycobacterium lacticolum 121 and the biosynthesis of polysaccharide are optimal at pH 8.0 to 8.2. Changes in acidity of the medium have no effect on the qualitative composition, structure, and molecular weight of the polysaccharide."}
{"id": "PMID:1633", "title": "[Effect of H+ and OH- ions on the physiological and biochemical properties of a Pseudomonas methanolica culture].", "content": "The growth of Pseudomonas methanolica was inhibited by unfavourable values of pH in the conditions of chemostat; the rate of the substrate assimilation was higher, and anabolic and catabolic reactions were decoupled. Hydrogen ions inhibited the activity of enzymes of the Krebs cycle, hydroxyl ions inhibited the activity of methanol dehydrogenase. Changes in pH are presumed to involve the energy apparatus of the cell membrane.", "contents": "[Effect of H+ and OH- ions on the physiological and biochemical properties of a Pseudomonas methanolica culture]. The growth of Pseudomonas methanolica was inhibited by unfavourable values of pH in the conditions of chemostat; the rate of the substrate assimilation was higher, and anabolic and catabolic reactions were decoupled. Hydrogen ions inhibited the activity of enzymes of the Krebs cycle, hydroxyl ions inhibited the activity of methanol dehydrogenase. Changes in pH are presumed to involve the energy apparatus of the cell membrane."}
{"id": "PMID:1639", "title": "[Panarteritis nodosa-Special aspects of glucocorticoid and immune suppressive therapy (author's transl)].", "content": "Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis.", "contents": "[Panarteritis nodosa-Special aspects of glucocorticoid and immune suppressive therapy (author's transl)]. Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis."}
{"id": "PMID:1634", "title": "[Factors causing lysis of an Actinomyces rimosus culture, the producer of the antibiotic, oxytetracycline].", "content": "The lysis of Actinomyces rimosus producing oxytetracycline during its mass growth can be caused by two factors which were separated by differential centrifugation. The first factor is phage particles of a temperate phage produced by the culture; they are incapable of growth but may induce the lysis. The phage particles treated with low pH and a temperature of 70 degrees C lose the lytic activity. The second factor is a lytic enzyme produced under the control of the temperate phage during its induction; it seems to consist of at least two enzymes, a lytic enzyme and a proteolytic enzyme.", "contents": "[Factors causing lysis of an Actinomyces rimosus culture, the producer of the antibiotic, oxytetracycline]. The lysis of Actinomyces rimosus producing oxytetracycline during its mass growth can be caused by two factors which were separated by differential centrifugation. The first factor is phage particles of a temperate phage produced by the culture; they are incapable of growth but may induce the lysis. The phage particles treated with low pH and a temperature of 70 degrees C lose the lytic activity. The second factor is a lytic enzyme produced under the control of the temperate phage during its induction; it seems to consist of at least two enzymes, a lytic enzyme and a proteolytic enzyme."}
{"id": "PMID:1638", "title": "[Pulmonary vascular pressures and blood gases in young patients with thoracic scoliosis (author's transl)].", "content": "Pulmonary artery and pulmonary wedge pressures were measured at rest and during exercise in 25 young patients with moderate to severe scoliosis. Simultaneous determinations of arterial blood gases and pH were performed. The results of the vascular pressure measurements were compared with those obtained in 15 healthy young subjects. In all patients the pulmonary artery and pulmonary wedge pressure were normal at rest. During mild ergometer exercise, however, an abnormal rise in pulmonary artery pressure occurred in 9 patients. Moreover, an increased diastolic pressure gradient across the pulmonary vascular bed was found in some scoliotic patients indicating an elevated pulmonary vascular resistance. It is supposed that this haemodynamic abnormality is primarily due to a restriction of the pulmonary vascular bed. Relationships between pulmonary artery pressure and arterial oxygen tension and blood pH, respectively, could be found. The possible significance of these results is discussed.", "contents": "[Pulmonary vascular pressures and blood gases in young patients with thoracic scoliosis (author's transl)]. Pulmonary artery and pulmonary wedge pressures were measured at rest and during exercise in 25 young patients with moderate to severe scoliosis. Simultaneous determinations of arterial blood gases and pH were performed. The results of the vascular pressure measurements were compared with those obtained in 15 healthy young subjects. In all patients the pulmonary artery and pulmonary wedge pressure were normal at rest. During mild ergometer exercise, however, an abnormal rise in pulmonary artery pressure occurred in 9 patients. Moreover, an increased diastolic pressure gradient across the pulmonary vascular bed was found in some scoliotic patients indicating an elevated pulmonary vascular resistance. It is supposed that this haemodynamic abnormality is primarily due to a restriction of the pulmonary vascular bed. Relationships between pulmonary artery pressure and arterial oxygen tension and blood pH, respectively, could be found. The possible significance of these results is discussed."}
{"id": "PMID:1674", "title": "Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism.", "content": "We studied the relative importance of hyperkalemia and mineralocorticoid deficiency in the metabolic acidosis of a patient with proved isolated hyporeninemic hypoaldosteronism and moderate kidney failure. The hyperkalemia and acidosis were severe in relation to the slight azotemia. Despite the systemic acidosis and urinary pH of 4.9, urinary ammonium excretion was distinctly blunted. Correction of the hyperkalemia by potassium-sodium exchange resin alone resolved the acidosis and restored the previously diminished urinary ammonium excretion to normal. Administration of mineralocorticoids only partially corrected the hyperkalemia and the acidosis. Hyperkalemia by itself, rather than hypoaldosteronism per se, caused the acidosis in this patient. Hyperkalemia apparently suppresses urinary ammonium excretion and thus interferes with urinary acidification.", "contents": "Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. We studied the relative importance of hyperkalemia and mineralocorticoid deficiency in the metabolic acidosis of a patient with proved isolated hyporeninemic hypoaldosteronism and moderate kidney failure. The hyperkalemia and acidosis were severe in relation to the slight azotemia. Despite the systemic acidosis and urinary pH of 4.9, urinary ammonium excretion was distinctly blunted. Correction of the hyperkalemia by potassium-sodium exchange resin alone resolved the acidosis and restored the previously diminished urinary ammonium excretion to normal. Administration of mineralocorticoids only partially corrected the hyperkalemia and the acidosis. Hyperkalemia by itself, rather than hypoaldosteronism per se, caused the acidosis in this patient. Hyperkalemia apparently suppresses urinary ammonium excretion and thus interferes with urinary acidification."}
{"id": "PMID:1676", "title": "Isolation of Penicillium corylophium Dierckx from acid mine water and its optimal growth on hydrocarbons at acid pH.", "content": "Penicillium corylophilium Dieckx was isolated from sludge collected at the interface of an aqueous, copper-bearing leachate and an organic, kerosene based, ion exchange solvent. The organism assimilated kerosene and various straight chain and cyclic hydrocarbons including dodecane, hexadecane, octadecane, toluene, benzene, and cyclohexane. Assimilation of kerosene and hexadecane was optimal at pH 2 and was stimulated by yeast extract.", "contents": "Isolation of Penicillium corylophium Dierckx from acid mine water and its optimal growth on hydrocarbons at acid pH. Penicillium corylophilium Dieckx was isolated from sludge collected at the interface of an aqueous, copper-bearing leachate and an organic, kerosene based, ion exchange solvent. The organism assimilated kerosene and various straight chain and cyclic hydrocarbons including dodecane, hexadecane, octadecane, toluene, benzene, and cyclohexane. Assimilation of kerosene and hexadecane was optimal at pH 2 and was stimulated by yeast extract."}
{"id": "PMID:1677", "title": "The effect of microbial mycolytic agents on Trichophyton rubrum.", "content": "Chitinolytic microorganisms isolated from forest soil and from healthy gypsy moth larvae (Porthetria dispar (L.) were screened for their ability to lyse Trichophyton rubrum mycelia. A few of these isolates were mycolytic on both autoclaved and on actively growing, intact, T. rubrum mycelia. Supernatants from these isolates, utilizing live T. rubrum as the sole carbon source, showed the same mycolytic ability. Assays of the supernatants for enzymatic activity revealed exocellular, stable enzymes that releases reducing substances including N-acetylglucosamine from the mycelia.", "contents": "The effect of microbial mycolytic agents on Trichophyton rubrum. Chitinolytic microorganisms isolated from forest soil and from healthy gypsy moth larvae (Porthetria dispar (L.) were screened for their ability to lyse Trichophyton rubrum mycelia. A few of these isolates were mycolytic on both autoclaved and on actively growing, intact, T. rubrum mycelia. Supernatants from these isolates, utilizing live T. rubrum as the sole carbon source, showed the same mycolytic ability. Assays of the supernatants for enzymatic activity revealed exocellular, stable enzymes that releases reducing substances including N-acetylglucosamine from the mycelia."}
{"id": "PMID:1680", "title": "Models for metal ion function in carbonic anhydrase.", "content": "A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme.", "contents": "Models for metal ion function in carbonic anhydrase. A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme."}
{"id": "PMID:1682", "title": "[Regulation of lipid synthesis in animal organs].", "content": "Studies were made of the mechanisms regulating the quantity and catalytic efficiency of hepatic acetyl coenzyme A carboxylase, which plays a critical role in the control of fatty acid biosynthesis. The microsomal enzyme system responsible for the formation of phosphatidic acid, the initial step in glycerolipid biosynthesis, was resolved into two component enzymes. The acyl-donor specificities of these and other acyltransferases account for the asymmetric fatty acid distribution in naturally occurring glycerolipids.", "contents": "[Regulation of lipid synthesis in animal organs]. Studies were made of the mechanisms regulating the quantity and catalytic efficiency of hepatic acetyl coenzyme A carboxylase, which plays a critical role in the control of fatty acid biosynthesis. The microsomal enzyme system responsible for the formation of phosphatidic acid, the initial step in glycerolipid biosynthesis, was resolved into two component enzymes. The acyl-donor specificities of these and other acyltransferases account for the asymmetric fatty acid distribution in naturally occurring glycerolipids."}
{"id": "PMID:1684", "title": "Comparison of properties between virulent and attenuated strains of transmissible gastroenteritis virus.", "content": "Strains of transmissible gastroenteritis (TGE) virus possessing different pathogenicity were examined for stability to digestive enzymes and acid, and growth at various temperatures. In growth experiments, virus titer obtained at 37 degrees C were about equal between attenuated and virulent strains, but titers attained by the attenuated strain were higher at 30 degrees C. The attenuated virus multiplied at 28 degrees C, but the virulent virus did not at this temperature. The virulent virus was significantly stable to trypsin and pepsin, but the attenuated virus was inactivated rapidly by these proteolytic enzymes. No significant differences were observed in stability to acid between the attenuated and virulent strains. At different pH, both lost their infectivity more rapidly at 37 degrees C than at 22 degrees C.", "contents": "Comparison of properties between virulent and attenuated strains of transmissible gastroenteritis virus. Strains of transmissible gastroenteritis (TGE) virus possessing different pathogenicity were examined for stability to digestive enzymes and acid, and growth at various temperatures. In growth experiments, virus titer obtained at 37 degrees C were about equal between attenuated and virulent strains, but titers attained by the attenuated strain were higher at 30 degrees C. The attenuated virus multiplied at 28 degrees C, but the virulent virus did not at this temperature. The virulent virus was significantly stable to trypsin and pepsin, but the attenuated virus was inactivated rapidly by these proteolytic enzymes. No significant differences were observed in stability to acid between the attenuated and virulent strains. At different pH, both lost their infectivity more rapidly at 37 degrees C than at 22 degrees C."}
{"id": "PMID:1685", "title": "Growth of Ibaraki virus in suspension culture of HmLu-1 cells.", "content": "The established hamster lung cell line, HmLu-1 cells could grow in a suspended state. The initial cell count, 40 X 10(4)/ml, increased to 200 X 10(4)/ml on the 4th day of culture. The suspension culture of HmLu-1 cells was proved satisfactory for propagation of Ibaraki virus. The viral titer reached a maximum of 10(6.75) TCID50/0.1 ml. The input multiplicity ranging from 0.003 to 3.0 exerted no influence on the final yield of the virus. The optimal pH value of initial culture ranged from 6.8 to 7.6. In comparison of virus yield per cell among the suspension culture and two methods of monolayer culture in stationary and rolling condition, there was no noticeable difference in it among the three methods. The cell population per unit volume was the largest and, therefore, virus titer in the culture fluid the highest in the suspension culture of the three methods.", "contents": "Growth of Ibaraki virus in suspension culture of HmLu-1 cells. The established hamster lung cell line, HmLu-1 cells could grow in a suspended state. The initial cell count, 40 X 10(4)/ml, increased to 200 X 10(4)/ml on the 4th day of culture. The suspension culture of HmLu-1 cells was proved satisfactory for propagation of Ibaraki virus. The viral titer reached a maximum of 10(6.75) TCID50/0.1 ml. The input multiplicity ranging from 0.003 to 3.0 exerted no influence on the final yield of the virus. The optimal pH value of initial culture ranged from 6.8 to 7.6. In comparison of virus yield per cell among the suspension culture and two methods of monolayer culture in stationary and rolling condition, there was no noticeable difference in it among the three methods. The cell population per unit volume was the largest and, therefore, virus titer in the culture fluid the highest in the suspension culture of the three methods."}
{"id": "PMID:1686", "title": "Studies on the mechanism of the action of morphine on the peristalsis of guinea pig ileum in situ.", "content": "The influence of some drugs on the effect of morphine on the threshold pressure required to elicit peristalsis in the guinea pig ileum in situ was studied, in order to test the hypothesis that this effect of morphine is mediated by catecholamine release. Tachyphylaxis to this effect of morphine was confirmed. Pretreatemnt with two 8 mg/kg doses of reserpine, 24 and 48 hrs before the experiment, significantly reduced the effect of morphine on the pressure threshold. The i.v. administration of 10 mg/kg dl-Dopa re-established the effect of morphine in reserpinized animals to the level of the untreated controls. Pretreatment with guanethidine (15 mg/kg) decreased and even prevented this effect of morphine. Phentolamine pretreatment (10 mg/kg) also significantly inhibited the effect of morphine. Neither DCI nor propranolol influenced this morphine effect. Pretreatment with reserpine, guanethidine or phentolamine reduced the basic pressure threshold needed to elicit peristalsis. The possibility that the decrease of local circulation induced by hypotenison would reduce the local concentration of morphine was rejected because the same doses of guanethidine or phentolamine did not modify the effect of hexamethonium given i.v. in this preparation. All these results support the idea that the effect of morphine on intestinal peristalsis is mediated by a catecholamine acting on alpha-receptors, e.g. norepinephrine.", "contents": "Studies on the mechanism of the action of morphine on the peristalsis of guinea pig ileum in situ. The influence of some drugs on the effect of morphine on the threshold pressure required to elicit peristalsis in the guinea pig ileum in situ was studied, in order to test the hypothesis that this effect of morphine is mediated by catecholamine release. Tachyphylaxis to this effect of morphine was confirmed. Pretreatemnt with two 8 mg/kg doses of reserpine, 24 and 48 hrs before the experiment, significantly reduced the effect of morphine on the pressure threshold. The i.v. administration of 10 mg/kg dl-Dopa re-established the effect of morphine in reserpinized animals to the level of the untreated controls. Pretreatment with guanethidine (15 mg/kg) decreased and even prevented this effect of morphine. Phentolamine pretreatment (10 mg/kg) also significantly inhibited the effect of morphine. Neither DCI nor propranolol influenced this morphine effect. Pretreatment with reserpine, guanethidine or phentolamine reduced the basic pressure threshold needed to elicit peristalsis. The possibility that the decrease of local circulation induced by hypotenison would reduce the local concentration of morphine was rejected because the same doses of guanethidine or phentolamine did not modify the effect of hexamethonium given i.v. in this preparation. All these results support the idea that the effect of morphine on intestinal peristalsis is mediated by a catecholamine acting on alpha-receptors, e.g. norepinephrine."}
{"id": "PMID:1687", "title": "Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets.", "content": "In perifused isolated pancreatic islets alpha-ketoisocaproic acid (KIC) or alpha-ketocaproic acid (KC) induced a high insulin secretion rate and a steep increase of the fluorescence of reduced pyridine pyridine nucleotides [NAD(P)H] which fell again to almost prestimulatory levels 6 min after medium change. Insulin release in response to alpha-ketooctanoic (KO) acid started slowly and was accompanied by a decrease of the NAD(P)H-fluorescence trace. Beta-phenylpyruvate which is known to initiate insulin release also caused a fluorescence decrease. Alpha-keto-isovaleric (KIV) acid or pyruvate had no significant effects upon insulin secretion or NAD(P)H-fluorescence. In contrast to l-leucine, l-norleucine or l-valine did not enhance insulin release or fluorescence of NAD(P)H. KIV, alpha-keto-beta-methylvaleric acid (KMV), KIC and KC raised the production their corresponding amino acids by islet cells. From these results it is concluded that alpha-ketomonocarboxylic acids as such trigger insulin release by acting upon receptor sites which differ from those occupied by amino acids.", "contents": "Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets. In perifused isolated pancreatic islets alpha-ketoisocaproic acid (KIC) or alpha-ketocaproic acid (KC) induced a high insulin secretion rate and a steep increase of the fluorescence of reduced pyridine pyridine nucleotides [NAD(P)H] which fell again to almost prestimulatory levels 6 min after medium change. Insulin release in response to alpha-ketooctanoic (KO) acid started slowly and was accompanied by a decrease of the NAD(P)H-fluorescence trace. Beta-phenylpyruvate which is known to initiate insulin release also caused a fluorescence decrease. Alpha-keto-isovaleric (KIV) acid or pyruvate had no significant effects upon insulin secretion or NAD(P)H-fluorescence. In contrast to l-leucine, l-norleucine or l-valine did not enhance insulin release or fluorescence of NAD(P)H. KIV, alpha-keto-beta-methylvaleric acid (KMV), KIC and KC raised the production their corresponding amino acids by islet cells. From these results it is concluded that alpha-ketomonocarboxylic acids as such trigger insulin release by acting upon receptor sites which differ from those occupied by amino acids."}
{"id": "PMID:1689", "title": "The preparation and properties of nerve growth factor protein at alkaline pH.", "content": "The nerve growth factor (NGF) subunit of 7S NGF was isolated by chromatography at high pH on QAE-Sephadex. It has the same specific NGF activity as betaNGF isolated at acid pH, showing that this activity is an intrinsic property of the subunit and is independent of the pathway of dissociation. Continued exposure of the NGF subunit to high pH resulted in an increase in the amount of the minor species beta2NGF and the formation of a new species, beta3NGF, of even lower isoelectric point. These two species and the original major species of the preparation, beta1, were isolated by isoelectric focusing. All three species had the same specific NGF activity, but differed in their ability to reform 7S NGF. The beta2 species was one-fifth as competent as beta1, while beta3 was unable to regenerate 7S NGF. Addition of alpha- and gamma-subunits to beta1NGF decreased the amount of NGF protein required to produce one Biological Unit of activity in the bioassay, but had no effect when added to beta3NGF. The interactions between the subunits in 7S NGF therefore determine, in part, the specific activity of the NGF subunit.", "contents": "The preparation and properties of nerve growth factor protein at alkaline pH. The nerve growth factor (NGF) subunit of 7S NGF was isolated by chromatography at high pH on QAE-Sephadex. It has the same specific NGF activity as betaNGF isolated at acid pH, showing that this activity is an intrinsic property of the subunit and is independent of the pathway of dissociation. Continued exposure of the NGF subunit to high pH resulted in an increase in the amount of the minor species beta2NGF and the formation of a new species, beta3NGF, of even lower isoelectric point. These two species and the original major species of the preparation, beta1, were isolated by isoelectric focusing. All three species had the same specific NGF activity, but differed in their ability to reform 7S NGF. The beta2 species was one-fifth as competent as beta1, while beta3 was unable to regenerate 7S NGF. Addition of alpha- and gamma-subunits to beta1NGF decreased the amount of NGF protein required to produce one Biological Unit of activity in the bioassay, but had no effect when added to beta3NGF. The interactions between the subunits in 7S NGF therefore determine, in part, the specific activity of the NGF subunit."}
{"id": "PMID:1690", "title": "Concanavalin A-binding glycopeptides from rat brain glycoproteins.", "content": "The affinity of concanavalin A for neutral and acidic glycopeptides derived from rat brain glycoproteins was investigated by studying the inhibition of a concanavalin A-glycogen precipitation system. The neutral, mannose-rich glycopeptides obtained by column electrophoresis of the dialyzable glycopeptides that had been solubilized by proteolytic treatment of defatted brain tissue were powerful inhibitors, with an inhibitory activity 20 to 26 times that of the standard inhibitor, methyl-alpha-D-mannoside. The acidic sialoglycopeptides had activities one to nine times that of the mannoside. Therefore, both acid and neutral glycopeptides were capable of interacting with concanavalin A. The especially strong affinity of the neutral mannose-rich glycopeptides, however, enabled their retention on concanavalin A-Sepharose and subsequent elution with methyl-alpha-D-mannoside. This provided the means of separation of the acidic sialoglycopeptides from the neutral, mannose-rich glycopeptides by affinity chromatography. Glycopeptides that contain N-acetylgalactosamine are not retained by concanavalin A-Sepharose.", "contents": "Concanavalin A-binding glycopeptides from rat brain glycoproteins. The affinity of concanavalin A for neutral and acidic glycopeptides derived from rat brain glycoproteins was investigated by studying the inhibition of a concanavalin A-glycogen precipitation system. The neutral, mannose-rich glycopeptides obtained by column electrophoresis of the dialyzable glycopeptides that had been solubilized by proteolytic treatment of defatted brain tissue were powerful inhibitors, with an inhibitory activity 20 to 26 times that of the standard inhibitor, methyl-alpha-D-mannoside. The acidic sialoglycopeptides had activities one to nine times that of the mannoside. Therefore, both acid and neutral glycopeptides were capable of interacting with concanavalin A. The especially strong affinity of the neutral mannose-rich glycopeptides, however, enabled their retention on concanavalin A-Sepharose and subsequent elution with methyl-alpha-D-mannoside. This provided the means of separation of the acidic sialoglycopeptides from the neutral, mannose-rich glycopeptides by affinity chromatography. Glycopeptides that contain N-acetylgalactosamine are not retained by concanavalin A-Sepharose."}
{"id": "PMID:1691", "title": "The use of hybrid molecules in a study of the equilibrium between nerve growth factor monomers and dimers.", "content": "The major protein in beta nerve growth factor preparations, beta1NGF, is a dimer in which both peptide chains have COOH-terminal arginine residues. Digestion of beta1NGF with carboxypeptidase B produced a dimer, beta3NGF, in which both chains lack these terminal arginine residues. Exposure of mixtures of beta1 and beta3NGF dimers to 8 M urea to produce monomers, followed by removal of urea to allow recombination, resulted in the formation of the hybrid beta2NGF, comprising one arginine-containing and one arginine-less chain, as well as the parent dimers. The amount of the three dimers formed was close to that expected from random association of monomers. Hybrid beta2NGF was also formed from mixtures of beta1 and beta3NGF where incubated at pH 2.6 to 4.5. The formation of beta2NGF has a half-time of 6 h at pH 4.0 and 4 degrees C. Its rate of formation decreased above pH 4.5, becoming minimal between pH 9.5 and pH 10.5, and increased with increasing temperature. The amount of beta2NGF formed was determined by the lowest pH to which the parent mixture was exposed, irrespective of its prior history. These data suggest that the hybrid is formed by the same mechanism in the absence and presence of the urea step. An approximate value for Kd, the equilibrium dissociation constant of the dimer equilibrium monomer equilibrium was derived. Its value was 3 - 10(-10) M at pH 4.0 and 4 degrees C. The alpha-subunit of 7S NGF decreased the rate of formation of beta2NGF not only at pHs where an alphabeta complex is stable, but also at an acid pH where no complex formation is observed by sedimentation analysis, suggesting that the present methodology offers a more sensitive probe of subunit interactions. In contrast, the gamma subunit and a number of indifferent proteins had little or no effect on the appearance of beta2NGF at the pHs studied.", "contents": "The use of hybrid molecules in a study of the equilibrium between nerve growth factor monomers and dimers. The major protein in beta nerve growth factor preparations, beta1NGF, is a dimer in which both peptide chains have COOH-terminal arginine residues. Digestion of beta1NGF with carboxypeptidase B produced a dimer, beta3NGF, in which both chains lack these terminal arginine residues. Exposure of mixtures of beta1 and beta3NGF dimers to 8 M urea to produce monomers, followed by removal of urea to allow recombination, resulted in the formation of the hybrid beta2NGF, comprising one arginine-containing and one arginine-less chain, as well as the parent dimers. The amount of the three dimers formed was close to that expected from random association of monomers. Hybrid beta2NGF was also formed from mixtures of beta1 and beta3NGF where incubated at pH 2.6 to 4.5. The formation of beta2NGF has a half-time of 6 h at pH 4.0 and 4 degrees C. Its rate of formation decreased above pH 4.5, becoming minimal between pH 9.5 and pH 10.5, and increased with increasing temperature. The amount of beta2NGF formed was determined by the lowest pH to which the parent mixture was exposed, irrespective of its prior history. These data suggest that the hybrid is formed by the same mechanism in the absence and presence of the urea step. An approximate value for Kd, the equilibrium dissociation constant of the dimer equilibrium monomer equilibrium was derived. Its value was 3 - 10(-10) M at pH 4.0 and 4 degrees C. The alpha-subunit of 7S NGF decreased the rate of formation of beta2NGF not only at pHs where an alphabeta complex is stable, but also at an acid pH where no complex formation is observed by sedimentation analysis, suggesting that the present methodology offers a more sensitive probe of subunit interactions. In contrast, the gamma subunit and a number of indifferent proteins had little or no effect on the appearance of beta2NGF at the pHs studied."}
{"id": "PMID:1692", "title": "Changes in hypothalamic neurotransmitter uptake following pinealectomy, superior cervical ganglionectomy or melatonin administration to rats.", "content": "Rats subjected to pinealectomy or to pinealectomy plus bilateral superior cervical ganglionectomy exhibited depressed serotonin uptake by hypothalamic synaptosomes; norepinephrine, dopamine or glutamate uptake was not affected by any of the surgical procedures. Treatment with melatonin resulted in inhibition of hypothalamic serotonin accumulation but it did not modify the uptake of norepinephrine, dopamine or glutamate. These data suggest a relationship between the pineal gland and the serotoninergic nerve endings of the hypothalamus.", "contents": "Changes in hypothalamic neurotransmitter uptake following pinealectomy, superior cervical ganglionectomy or melatonin administration to rats. Rats subjected to pinealectomy or to pinealectomy plus bilateral superior cervical ganglionectomy exhibited depressed serotonin uptake by hypothalamic synaptosomes; norepinephrine, dopamine or glutamate uptake was not affected by any of the surgical procedures. Treatment with melatonin resulted in inhibition of hypothalamic serotonin accumulation but it did not modify the uptake of norepinephrine, dopamine or glutamate. These data suggest a relationship between the pineal gland and the serotoninergic nerve endings of the hypothalamus."}
{"id": "PMID:1695", "title": "Timolol maleate (Blocadren) in the treatment of essential hypertension.", "content": "The antihypertensive activity of timolol (Blocadren, FROSST-MSD), a new beta blocking agent, was assessed in a single blind crossover placebo-controlled study in 14 patients with essential hypertension. Ten patients completed the trial. The average standing pressure during the placebos periods was 168/109mmHg and during the periods on treatment with timolol the average standing pressure was 139/92mmHg. All 10 patients showed some hypotensive response. The average daily dosage was 21 mg with a range of 15-30 mg. Four patients achieved optimal levels of blood pressure by the end of one week's therapy with the maximum time required being four weeks. Timolol appears to be an effective antihypertensive agent. Side effects were insignificant.", "contents": "Timolol maleate (Blocadren) in the treatment of essential hypertension. The antihypertensive activity of timolol (Blocadren, FROSST-MSD), a new beta blocking agent, was assessed in a single blind crossover placebo-controlled study in 14 patients with essential hypertension. Ten patients completed the trial. The average standing pressure during the placebos periods was 168/109mmHg and during the periods on treatment with timolol the average standing pressure was 139/92mmHg. All 10 patients showed some hypotensive response. The average daily dosage was 21 mg with a range of 15-30 mg. Four patients achieved optimal levels of blood pressure by the end of one week's therapy with the maximum time required being four weeks. Timolol appears to be an effective antihypertensive agent. Side effects were insignificant."}
{"id": "PMID:1696", "title": "Effects of ritodrine hydrochloride on uterine activity and the cardiovascular system in toxemic patients.", "content": "The effects of ritodrine hydrochloride were evaluated in 25 toxemic patients in active labor utilizing continuous electronic monitoring of fetal and maternal cardiovascular systems and uterine activity. Fetal scalp blood and free flowing maternal antecubital venous blood was obtained for pH, Po2, Pco2, base deficit and blood glucose determinations prior to and immediately following the study period. The initial ritodrine dose was 50 mug/min for 15 minutes. The dose was increased by 50 mug/min each 15 minutes until there was a clinically apparent reduction in uterine activity. Once this was accomplished, the infusion was maintained for 30 minutes. There was a consistent increase in the maternal heart rate (MHR) and a significant rise in fetal heart rate (FHR) late in the infusion and in the postinfusion period. There was a widening of the maternal pulse pressure mainly due to a reduction in diastolic pressure with little change in the mean blood pressure. Maternal and fetal pH decreased and base deficit increased during the study although the PO2 and PCO2 remained unchanged. Maternal and fetal blood glucose rose significantly following ritodrine infusion.", "contents": "Effects of ritodrine hydrochloride on uterine activity and the cardiovascular system in toxemic patients. The effects of ritodrine hydrochloride were evaluated in 25 toxemic patients in active labor utilizing continuous electronic monitoring of fetal and maternal cardiovascular systems and uterine activity. Fetal scalp blood and free flowing maternal antecubital venous blood was obtained for pH, Po2, Pco2, base deficit and blood glucose determinations prior to and immediately following the study period. The initial ritodrine dose was 50 mug/min for 15 minutes. The dose was increased by 50 mug/min each 15 minutes until there was a clinically apparent reduction in uterine activity. Once this was accomplished, the infusion was maintained for 30 minutes. There was a consistent increase in the maternal heart rate (MHR) and a significant rise in fetal heart rate (FHR) late in the infusion and in the postinfusion period. There was a widening of the maternal pulse pressure mainly due to a reduction in diastolic pressure with little change in the mean blood pressure. Maternal and fetal pH decreased and base deficit increased during the study although the PO2 and PCO2 remained unchanged. Maternal and fetal blood glucose rose significantly following ritodrine infusion."}
{"id": "PMID:1697", "title": "Treatment of ovarian hyperstimulation syndrome by antihistamine.", "content": "Ovarian hyperstimulation was produced by human menopausal gonadotropin and chorionic gonadotropin in rabbits. A more rapid regression of the hyperstimualted ovaries was observed in an antihistamine-treated group than in a control group. The difference in regression was found to be statistically significant. The possibility of treating the ovarian hyperstimulation syndrome by antihistamine is cited.", "contents": "Treatment of ovarian hyperstimulation syndrome by antihistamine. Ovarian hyperstimulation was produced by human menopausal gonadotropin and chorionic gonadotropin in rabbits. A more rapid regression of the hyperstimualted ovaries was observed in an antihistamine-treated group than in a control group. The difference in regression was found to be statistically significant. The possibility of treating the ovarian hyperstimulation syndrome by antihistamine is cited."}
{"id": "PMID:1698", "title": "High pH ammonia toxicity, and the search for life on the Jovian planets.", "content": "Jovian plants have enviroments apparently suitable for the evolution of life, but nevertheless, present severe challenges to organisms. One such challenge arises from the presence of ammonia. Ammonia is an efficient biocide, its effect being dependent on pH as well as on concentration. The effects of pH and ammonia concentration were studied separately, where possible, on a variety of organisms, including some isolated from natural enviornments of high pH and/or ammonia concentration. Escherichia coli and Bacillus subtilis are both extremely sensitive to ammonia. An aerobic organism (growth up to pH 11.4) from an alkaline spring is more resistant, but exhibits a toxic response to ammonia at a pH much lower than its maximum for growth. The greatest ammonia resistance has been found in an unidentified organism growing at near neutral pH. Even in this case, however, survival at ammonia concentrations reasonably expected on the Jovian planets is measured in hours. This is, nevertheless, two to three orders of magnitude longer than for E. coli. Our data support the tentative conclusion that contamination of the Jovian planets with terrestrial organisms that can grow is unlikely. However, the range of toxic response noted, coupled with the observation that terrestrial life has not been exposed to high ammonia concentrations for millions of years, suggests that adaptation to greater ammonia tolerance may be possible.", "contents": "High pH ammonia toxicity, and the search for life on the Jovian planets. Jovian plants have enviroments apparently suitable for the evolution of life, but nevertheless, present severe challenges to organisms. One such challenge arises from the presence of ammonia. Ammonia is an efficient biocide, its effect being dependent on pH as well as on concentration. The effects of pH and ammonia concentration were studied separately, where possible, on a variety of organisms, including some isolated from natural enviornments of high pH and/or ammonia concentration. Escherichia coli and Bacillus subtilis are both extremely sensitive to ammonia. An aerobic organism (growth up to pH 11.4) from an alkaline spring is more resistant, but exhibits a toxic response to ammonia at a pH much lower than its maximum for growth. The greatest ammonia resistance has been found in an unidentified organism growing at near neutral pH. Even in this case, however, survival at ammonia concentrations reasonably expected on the Jovian planets is measured in hours. This is, nevertheless, two to three orders of magnitude longer than for E. coli. Our data support the tentative conclusion that contamination of the Jovian planets with terrestrial organisms that can grow is unlikely. However, the range of toxic response noted, coupled with the observation that terrestrial life has not been exposed to high ammonia concentrations for millions of years, suggests that adaptation to greater ammonia tolerance may be possible."}
{"id": "PMID:1703", "title": "Gamma-glutamyltranspeptidase in the rat liver after portacaval shunt.", "content": "Gamma-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 +/- 0.1 mumol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 +/- 97 to 1,058 +/- 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day. After PCS the GGTP activity exhibited a three- to sixfold increase (130 +/- 69 to 371 +/- 131) as compared with unoperated adult controls (53 +/- 13). the highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GTTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes.", "contents": "Gamma-glutamyltranspeptidase in the rat liver after portacaval shunt. Gamma-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 +/- 0.1 mumol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 +/- 97 to 1,058 +/- 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day. After PCS the GGTP activity exhibited a three- to sixfold increase (130 +/- 69 to 371 +/- 131) as compared with unoperated adult controls (53 +/- 13). the highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GTTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes."}
{"id": "PMID:1704", "title": "Cardiovascular effects of electrical stimulation of the forebrain in the fetal lamb.", "content": "Modified stereotaxic techniques were applied to fetal lambs during the latter third of gestation. Electrical stimulation in the region of the hypothalamus in 10 acute experiments was associated with three patterns of arterial blood pressure and heart rate changes: a pressor-tachycardia response; a pure tachycardia response (abolished by propranolol); and a pure bradycardia response (abolished by atropine). The pressor-tachycardia response was examined in detail in 13 chronic preparations (115-135 days of gestation at operation). The systolic arterial blood pressure increase was never greater than 35 mm Hg and was probably blunted by the large noninnervated placental circulation. This pressure increase was abolished by phentolamine and was thus mediated by stimulation of alpha-adrenergic receptors. The initial tachycardia was prevented by propranolol and was due to beta-adrenergic stimulation. The tachycardia was followed in a few seconds by a bradycardia, abolished by atropine and possibly a vagal baroreflex. The pressor-tachycardia response was accentuated in two lambs who were delivered spontaneously and were studied after birth. These studies indicate that a suprabulbar neural framework exists in the fetal lamb for influencing the cardiovascular system from as early as 90 days of gestation.", "contents": "Cardiovascular effects of electrical stimulation of the forebrain in the fetal lamb. Modified stereotaxic techniques were applied to fetal lambs during the latter third of gestation. Electrical stimulation in the region of the hypothalamus in 10 acute experiments was associated with three patterns of arterial blood pressure and heart rate changes: a pressor-tachycardia response; a pure tachycardia response (abolished by propranolol); and a pure bradycardia response (abolished by atropine). The pressor-tachycardia response was examined in detail in 13 chronic preparations (115-135 days of gestation at operation). The systolic arterial blood pressure increase was never greater than 35 mm Hg and was probably blunted by the large noninnervated placental circulation. This pressure increase was abolished by phentolamine and was thus mediated by stimulation of alpha-adrenergic receptors. The initial tachycardia was prevented by propranolol and was due to beta-adrenergic stimulation. The tachycardia was followed in a few seconds by a bradycardia, abolished by atropine and possibly a vagal baroreflex. The pressor-tachycardia response was accentuated in two lambs who were delivered spontaneously and were studied after birth. These studies indicate that a suprabulbar neural framework exists in the fetal lamb for influencing the cardiovascular system from as early as 90 days of gestation."}
{"id": "PMID:1705", "title": "Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lymph node syndrome.", "content": "Mucocutaneous lymph node syndrome (MCLS) is a newly recognized disease characterized by fever persisting for more than 5 days, an erythematous skin eruption, conjunctival congestion, dry red fissured lips, reddened tongue, palms, and soles, nonpurulent lymphadenopathy, and sometines diarrhea, arthralgia, and aseptic meningitis. Additional features may include carditis, pericarditis, aneurysmal dilation and thrombosis of coronary arteries, and sudden death. There is a striking similarity of fatal cases to infantile polyarteritis nodosa, a disease recently reported to be associated with elevated levels of serium IgE. Indeed, it is likely that MCLS represents a disease which can progress to polyarteritis nodosa in infants and young children. The paired acute and convalescent serum IgE levels of 20 subjects with acute nonfatal MCLS were studied along with 20 near-age unaffected controls from the same communities in Japan. The results indicate that most if not all subjects with MCLS in the study had an elevation of total serum IgE during the acute phase of the disease (geometric mean 157 IU/ml compared with the control value of 38 IU/ml, P = 0.005). The level appeared to reach a peak 1-2 weeks after onset and declined over the ensuing 1-2 months.", "contents": "Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lymph node syndrome. Mucocutaneous lymph node syndrome (MCLS) is a newly recognized disease characterized by fever persisting for more than 5 days, an erythematous skin eruption, conjunctival congestion, dry red fissured lips, reddened tongue, palms, and soles, nonpurulent lymphadenopathy, and sometines diarrhea, arthralgia, and aseptic meningitis. Additional features may include carditis, pericarditis, aneurysmal dilation and thrombosis of coronary arteries, and sudden death. There is a striking similarity of fatal cases to infantile polyarteritis nodosa, a disease recently reported to be associated with elevated levels of serium IgE. Indeed, it is likely that MCLS represents a disease which can progress to polyarteritis nodosa in infants and young children. The paired acute and convalescent serum IgE levels of 20 subjects with acute nonfatal MCLS were studied along with 20 near-age unaffected controls from the same communities in Japan. The results indicate that most if not all subjects with MCLS in the study had an elevation of total serum IgE during the acute phase of the disease (geometric mean 157 IU/ml compared with the control value of 38 IU/ml, P = 0.005). The level appeared to reach a peak 1-2 weeks after onset and declined over the ensuing 1-2 months."}
{"id": "PMID:1706", "title": "Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome.", "content": "Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis.", "contents": "Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome. Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis."}
{"id": "PMID:1707", "title": "pH and bicarbonate excretion in the rat parotid gland as a function of salivary rate.", "content": "The bicarbonate concentration in rat parotid saliva increases with increasing flow rates and approximates plasma values at highest salivation. At lowest flow rates the bicarbonate concentration in the secretory fluid markedly exceeds the plasma levels. Intravenous administration of acetazolamide has no influence on the bicarbonate excretion of the parotid gland. Following retrograde application of acetazolamide into the gland duct the concentrations of both bicarbonate and sodium are elevated. The potassium concentrations in final saliva exceed 70 mEq/l at flow rates below 5 mul/min g gland weight. With increasing flow rates a precipitous decrease in potassium concentration below 10 mEq/l occurs. With further increase in flow rate the potassium concentration remains unchanged. The sodium concentrations increased with augmented salivation rate. At lowest flow rates the sodium concentrations showed an increase of modest degree. Our findings can best be explained by the existence of two independent ductular mechanism: a) bicarbonate reabsorption probably in the striated ducts of the parotid gland; b) secretion of potassium with concomitand secretion of bicarbonate in the main excretory duct.", "contents": "pH and bicarbonate excretion in the rat parotid gland as a function of salivary rate. The bicarbonate concentration in rat parotid saliva increases with increasing flow rates and approximates plasma values at highest salivation. At lowest flow rates the bicarbonate concentration in the secretory fluid markedly exceeds the plasma levels. Intravenous administration of acetazolamide has no influence on the bicarbonate excretion of the parotid gland. Following retrograde application of acetazolamide into the gland duct the concentrations of both bicarbonate and sodium are elevated. The potassium concentrations in final saliva exceed 70 mEq/l at flow rates below 5 mul/min g gland weight. With increasing flow rates a precipitous decrease in potassium concentration below 10 mEq/l occurs. With further increase in flow rate the potassium concentration remains unchanged. The sodium concentrations increased with augmented salivation rate. At lowest flow rates the sodium concentrations showed an increase of modest degree. Our findings can best be explained by the existence of two independent ductular mechanism: a) bicarbonate reabsorption probably in the striated ducts of the parotid gland; b) secretion of potassium with concomitand secretion of bicarbonate in the main excretory duct."}
{"id": "PMID:1708", "title": "H+ transport and membrane-bound HCO - 3 ATPase in salivary duct epithelium.", "content": "An ATPase stimulated by HCO -  ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO - 3 ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO - 3. The HCO - 3 ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'-nucleotidase. The activities of the HCO - 3 ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO - 3 and K+ ions by the duct epithelium. These findings provide further evidence that the membrane-bound HCO - 3 ATPase is involved in active H+/HCO - 3 transport.", "contents": "H+ transport and membrane-bound HCO - 3 ATPase in salivary duct epithelium. An ATPase stimulated by HCO -  ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO - 3 ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO - 3. The HCO - 3 ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'-nucleotidase. The activities of the HCO - 3 ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO - 3 and K+ ions by the duct epithelium. These findings provide further evidence that the membrane-bound HCO - 3 ATPase is involved in active H+/HCO - 3 transport."}
{"id": "PMID:1709", "title": "Effects of cyanide and doxapram during hypothermia.", "content": "The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and at two levels of hypothermia. In the normothermic animal, KCN evoked significant elevations of minute and alveolar ventilations. For the mildly hypothermic (32-33 degrees C) dog, minute and alveolar ventilations were proportionally greater than for normothermia. Bolus infusions of KCN to deeply hypothermic dogs (28-29 degrees C) elicited larger and nearly similar increases of minute and alveolar ventilations as compared, respectively, with normothermia and mild hypothermia. Compared to their controls, injections of doxapram during normothermia, mild and deep hypothermia augmented VE 43.3%, 63.6% and 31.5%, respectively. With doxapram there was a feeble increase in alveolar ventilation. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to respond to stimuli given acutely while lowering core temperature and in some circumstances this capacity is even enhanced as compared to normothermia.", "contents": "Effects of cyanide and doxapram during hypothermia. The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and at two levels of hypothermia. In the normothermic animal, KCN evoked significant elevations of minute and alveolar ventilations. For the mildly hypothermic (32-33 degrees C) dog, minute and alveolar ventilations were proportionally greater than for normothermia. Bolus infusions of KCN to deeply hypothermic dogs (28-29 degrees C) elicited larger and nearly similar increases of minute and alveolar ventilations as compared, respectively, with normothermia and mild hypothermia. Compared to their controls, injections of doxapram during normothermia, mild and deep hypothermia augmented VE 43.3%, 63.6% and 31.5%, respectively. With doxapram there was a feeble increase in alveolar ventilation. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to respond to stimuli given acutely while lowering core temperature and in some circumstances this capacity is even enhanced as compared to normothermia."}
{"id": "PMID:1710", "title": "Effects of cyanide and doxapram during panting.", "content": "The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic animal, KCN evoked elevation of VE (154.7%), VT (70.1%), f (48.3%, PaO2 (12.1%) and pH (0.098 units), while PaCO2 diminished by 9.7 mm Hg. During panting, KCN infusions resulted in increases of VE (24.5%), VT (46.6%), PaO2 (3.9%) and pH (0.034 units), while f decreased (10.1%). Bolus injections of doxapram during normothermia increased VE (32.6%), VT (18.8%) and f (17.1%). During panting VE, VT and f increased by 18.0%, 18.2% and 1.5%, respectively. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to react to acute chemical stimuli in animals in which the thermal stimuli override the normal chemical control of respiration in order to control body temperature, and that this reaction contributes to the integrated respiratory drive.", "contents": "Effects of cyanide and doxapram during panting. The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic animal, KCN evoked elevation of VE (154.7%), VT (70.1%), f (48.3%, PaO2 (12.1%) and pH (0.098 units), while PaCO2 diminished by 9.7 mm Hg. During panting, KCN infusions resulted in increases of VE (24.5%), VT (46.6%), PaO2 (3.9%) and pH (0.034 units), while f decreased (10.1%). Bolus injections of doxapram during normothermia increased VE (32.6%), VT (18.8%) and f (17.1%). During panting VE, VT and f increased by 18.0%, 18.2% and 1.5%, respectively. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to react to acute chemical stimuli in animals in which the thermal stimuli override the normal chemical control of respiration in order to control body temperature, and that this reaction contributes to the integrated respiratory drive."}
{"id": "PMID:1713", "title": "The effect of alpha-adrenolytics on the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in rat's brain.", "content": "Alpha-Adrenolytics (ABA)-phenoxybenzamine, phentolamine and aceperone-increase 5-hydroxyindoleacetic (5-HIAA) acid content in rat's brain. At the same time, these compounds either increase or do not affect 5-hydroxytryptamine (5-HT) level. Moreover, they potentiate L-dopa and reserpine-induced increase in 5-HIAA level and antagonized clonidine-induced decrease in 5-HIAA content. The experiments with probenecid indicate that the observed increase in 5-HIAA does not result from the deficient elimination of the metabolite from brain. The increase in 5-HT turnover in brain, due to ABA, is suggested.", "contents": "The effect of alpha-adrenolytics on the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in rat's brain. Alpha-Adrenolytics (ABA)-phenoxybenzamine, phentolamine and aceperone-increase 5-hydroxyindoleacetic (5-HIAA) acid content in rat's brain. At the same time, these compounds either increase or do not affect 5-hydroxytryptamine (5-HT) level. Moreover, they potentiate L-dopa and reserpine-induced increase in 5-HIAA level and antagonized clonidine-induced decrease in 5-HIAA content. The experiments with probenecid indicate that the observed increase in 5-HIAA does not result from the deficient elimination of the metabolite from brain. The increase in 5-HT turnover in brain, due to ABA, is suggested."}
{"id": "PMID:1717", "title": "Combating diabetic ketoacidosis and other hyperglycemic-ketoacidotic syndromes.", "content": "Diabetic ketoacidosis is an acute medical emergency that requires immediate diagnosis and treatment. Diagnosis may be established rapidly by measurement of urinary glucose and ketones, arterial blood pH and blood gases, and serum ketones. Rapid infusion of large volumes of fluids and electrolytes, together with continuous infusion of low doses of insulin, provides effective restoration of fluid and electrolyte balance and correction of metabolic derangements. Hyperosmolar nonketotic coma is characterized by marked hyperglycemia in the absence of ketoacidosis and occurs usually in patients with mild adult-onset diabetes. Symptoms develop more slowly than in diabetic ketoacidosis. Treatment is the same for both conditions. In alcoholic ketoacidosis, hyperketonemia is present without hyperglycemia. The syndrome differs from diabetic ketoacidosis in that blood glucose levels are lower and glycosuria is absent. Treatment consists of intravenous administration of dextrose in water and, if necessary, of sodium bicarbonate. Insulin administration usually is not necessary.", "contents": "Combating diabetic ketoacidosis and other hyperglycemic-ketoacidotic syndromes. Diabetic ketoacidosis is an acute medical emergency that requires immediate diagnosis and treatment. Diagnosis may be established rapidly by measurement of urinary glucose and ketones, arterial blood pH and blood gases, and serum ketones. Rapid infusion of large volumes of fluids and electrolytes, together with continuous infusion of low doses of insulin, provides effective restoration of fluid and electrolyte balance and correction of metabolic derangements. Hyperosmolar nonketotic coma is characterized by marked hyperglycemia in the absence of ketoacidosis and occurs usually in patients with mild adult-onset diabetes. Symptoms develop more slowly than in diabetic ketoacidosis. Treatment is the same for both conditions. In alcoholic ketoacidosis, hyperketonemia is present without hyperglycemia. The syndrome differs from diabetic ketoacidosis in that blood glucose levels are lower and glycosuria is absent. Treatment consists of intravenous administration of dextrose in water and, if necessary, of sodium bicarbonate. Insulin administration usually is not necessary."}
{"id": "PMID:1718", "title": "[Current conception of the Bohr effect].", "content": "The molecular mechanism of the Bohr effect is explained according to the molecular model proposed by Perutz et al. The Bohr effect is due to changes in the pK of specific carboxyl and amino groups of the four globin chains following the transition between the deoxy and oxy conformations of the molecule. Carbon dioxide binds to the N terminal valine of the 4 monomers to form carbamino compounds. This carbaminoformation depends upon pH, PCO2 and predominates on deoxygenated haemoglobin. It is lowered when O2 binds to the heme groups (O2 linked carbamino compounds). Through the carbamino compounds Carbon dioxide lowers both the affinity of haemoglobin for O2 and the Bohr effect. Diphosphoglycerate also binds to the haemoglogin molecule. This organophosphate lowers the affinity for O2 but increases the Bohr effect. In whole blood, the Bohr effect is therefore dependent upon pH, O2 saturation, PCO2 and DPG concentration into the red blood cells.", "contents": "[Current conception of the Bohr effect]. The molecular mechanism of the Bohr effect is explained according to the molecular model proposed by Perutz et al. The Bohr effect is due to changes in the pK of specific carboxyl and amino groups of the four globin chains following the transition between the deoxy and oxy conformations of the molecule. Carbon dioxide binds to the N terminal valine of the 4 monomers to form carbamino compounds. This carbaminoformation depends upon pH, PCO2 and predominates on deoxygenated haemoglobin. It is lowered when O2 binds to the heme groups (O2 linked carbamino compounds). Through the carbamino compounds Carbon dioxide lowers both the affinity of haemoglobin for O2 and the Bohr effect. Diphosphoglycerate also binds to the haemoglogin molecule. This organophosphate lowers the affinity for O2 but increases the Bohr effect. In whole blood, the Bohr effect is therefore dependent upon pH, O2 saturation, PCO2 and DPG concentration into the red blood cells."}
{"id": "PMID:1714", "title": "The central action of drugs influencing beta-adrenergic receptor. part V. The interaction of drugs affecting beta-adrenergic receptor in motility test.", "content": "Propranolol, alprenolol and sotalol given intraventricularly (ivc) to rats reduce depressing effects of isoprenaline (IPS) and antagonize stimulating effects of noradrenaline (NA). Phentolamine given by the same route of administration does not affect IPS action.", "contents": "The central action of drugs influencing beta-adrenergic receptor. part V. The interaction of drugs affecting beta-adrenergic receptor in motility test. Propranolol, alprenolol and sotalol given intraventricularly (ivc) to rats reduce depressing effects of isoprenaline (IPS) and antagonize stimulating effects of noradrenaline (NA). Phentolamine given by the same route of administration does not affect IPS action."}
{"id": "PMID:1719", "title": "[Study of P50 in patients under continuous O2 inhalation and during chronic respiratory acidosis].", "content": "In vitro, the affinity of Hb for O2 depends on pH and capnia by the intermediate of the 2-3 DPG level, the concentration of which lowers in the case of acidosis and hypercapnia. Thus, an increase in the affinity results, but while Bohr's effect is immediate, on the contrary the 2-3 DPG effect is slow. Authors have verified the importance of this modification by studying the affinity of Hb for O2 thanks to the P50 technique in 15 normal non-smokers subjects and in 10 subjects with compensated or not respiratory acidosis but normally saturated thanks to continuous O2 administration.", "contents": "[Study of P50 in patients under continuous O2 inhalation and during chronic respiratory acidosis]. In vitro, the affinity of Hb for O2 depends on pH and capnia by the intermediate of the 2-3 DPG level, the concentration of which lowers in the case of acidosis and hypercapnia. Thus, an increase in the affinity results, but while Bohr's effect is immediate, on the contrary the 2-3 DPG effect is slow. Authors have verified the importance of this modification by studying the affinity of Hb for O2 thanks to the P50 technique in 15 normal non-smokers subjects and in 10 subjects with compensated or not respiratory acidosis but normally saturated thanks to continuous O2 administration."}
{"id": "PMID:1715", "title": "The effect of alpha, alpha1-dipyridyl on noradrenaline, dopamine and 5-hydroxytryptamine levels and on dopamine-beta-hydroxylase activity in brain.", "content": "The effects of alpha, alpha1-dipyridyl (DP) on noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in rat and mouse brain and on dopamine-beta-hydroxylase (DbetaH) activity in rat brain have been studied, DP decreases NA level and inhibits DbetaH activity in a dose dependent manner, without affecting DA or 5-HT levels.", "contents": "The effect of alpha, alpha1-dipyridyl on noradrenaline, dopamine and 5-hydroxytryptamine levels and on dopamine-beta-hydroxylase activity in brain. The effects of alpha, alpha1-dipyridyl (DP) on noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in rat and mouse brain and on dopamine-beta-hydroxylase (DbetaH) activity in rat brain have been studied, DP decreases NA level and inhibits DbetaH activity in a dose dependent manner, without affecting DA or 5-HT levels."}
{"id": "PMID:1716", "title": "Colorimetric determination of bromisoval and carbromal.", "content": "New colorimetric procedure for determination of bromisoval and carbromal is based on the hydroxamation reaction and colour developing after addition of Fe(ClO4)3. The method is employed for the estimation of both compounds in substances and in tablets.", "contents": "Colorimetric determination of bromisoval and carbromal. New colorimetric procedure for determination of bromisoval and carbromal is based on the hydroxamation reaction and colour developing after addition of Fe(ClO4)3. The method is employed for the estimation of both compounds in substances and in tablets."}
{"id": "PMID:1720", "title": "[Effect of cultivation conditions on the synthesis of citric and isocitric acids in Candida lipolytica on hexadecane medium].", "content": "The influence of aeration, pH and iron concentration on the growth of yeast C. lipolytica 704 on the hexadecane medium and on the synthesis of citric and isocitric acids was investigated. The yeast synthesized citric acids actively during intensive aeration. The acid formation was strongly dependent on the medium acidity: pH 6.0 was most favourable  for the synthesis of citric acids. The Fe concentration influenced significantly the ratio of the acids synthesized. At a low concentration of iron (0.005 mg Fe/l) equal amounts of citrate and isocitrate were formed; at an increased concentration isocitrate was in predominant formation.", "contents": "[Effect of cultivation conditions on the synthesis of citric and isocitric acids in Candida lipolytica on hexadecane medium]. The influence of aeration, pH and iron concentration on the growth of yeast C. lipolytica 704 on the hexadecane medium and on the synthesis of citric and isocitric acids was investigated. The yeast synthesized citric acids actively during intensive aeration. The acid formation was strongly dependent on the medium acidity: pH 6.0 was most favourable  for the synthesis of citric acids. The Fe concentration influenced significantly the ratio of the acids synthesized. At a low concentration of iron (0.005 mg Fe/l) equal amounts of citrate and isocitrate were formed; at an increased concentration isocitrate was in predominant formation."}
{"id": "PMID:1721", "title": "[Study of inosine transformation into 5'-inosinic acid by the culture of Pseudomonas trifoli].", "content": "The transformation of inosine into 5'-inosine acid by Pseudomonas trifolii cells was studied. The synthesis of 5'-inosine acid can be performed by both live intact and dry cells. The effectiveness of inosine phosphorylation depends on the ratio of the inosine and phosphate donor concentrations and the amount of cells. The temperature and pH effect on activity of nucleoside phosphotransferase, phosphomonoesterase and 5'-nucleotidase has been studied. The influence of surface active substances and metal ions on the synthesis of 5'-inosine acid has been investigated. Optimal conditions for the inosine transformation by the above culture have been established.", "contents": "[Study of inosine transformation into 5'-inosinic acid by the culture of Pseudomonas trifoli]. The transformation of inosine into 5'-inosine acid by Pseudomonas trifolii cells was studied. The synthesis of 5'-inosine acid can be performed by both live intact and dry cells. The effectiveness of inosine phosphorylation depends on the ratio of the inosine and phosphate donor concentrations and the amount of cells. The temperature and pH effect on activity of nucleoside phosphotransferase, phosphomonoesterase and 5'-nucleotidase has been studied. The influence of surface active substances and metal ions on the synthesis of 5'-inosine acid has been investigated. Optimal conditions for the inosine transformation by the above culture have been established."}
{"id": "PMID:1722", "title": "[Effect of pH on the enzymic activity of the fungi Trichothecium roseum and Aspergillus niger hydrolyzing nonstarch polysaccharides].", "content": "The purpose of the study was to determine optimal pH values for the enzymic activity of the fungi Trichothecium roseum and Aspergillus niger hydrolyzing nonstarch polysaccharides of barley and disrupting cell walls (cytolysis) of grain, the so called cytolytic enzymes. The effect of the acidity of the medium on the stability of these enzymes was also investigated. In this connection total cytolytic activity (i. e. total activity of the enzymes hydrolyzing nonstarch polysaccharides of cell walls of barley) and hemicellulase activity of the fungi at different pH values were measured. The activity of these enzymes in aqueous extracts from the fungal culture at optimal pH after preincubation was determined at different acidity levels. The optimum of the hemicellulase activity of both fungi was at 4.6, the optimum of the total cytolytic activity of Tr. roseum at pH 5.6 and of Asp. niger at pH 3.0. The enzymes of the fungus Asp. niger showed a far higher acid stability than those of Tr. roseum.", "contents": "[Effect of pH on the enzymic activity of the fungi Trichothecium roseum and Aspergillus niger hydrolyzing nonstarch polysaccharides]. The purpose of the study was to determine optimal pH values for the enzymic activity of the fungi Trichothecium roseum and Aspergillus niger hydrolyzing nonstarch polysaccharides of barley and disrupting cell walls (cytolysis) of grain, the so called cytolytic enzymes. The effect of the acidity of the medium on the stability of these enzymes was also investigated. In this connection total cytolytic activity (i. e. total activity of the enzymes hydrolyzing nonstarch polysaccharides of cell walls of barley) and hemicellulase activity of the fungi at different pH values were measured. The activity of these enzymes in aqueous extracts from the fungal culture at optimal pH after preincubation was determined at different acidity levels. The optimum of the hemicellulase activity of both fungi was at 4.6, the optimum of the total cytolytic activity of Tr. roseum at pH 5.6 and of Asp. niger at pH 3.0. The enzymes of the fungus Asp. niger showed a far higher acid stability than those of Tr. roseum."}
{"id": "PMID:1723", "title": "[Study of the yeast dissolving enzymic complex by isoelectric focusing].", "content": "By isoelectric focussing the lyzing complex produced by Actinomyces griseinus-11 has been fractionated. The sole neutral protease which is active at pH 7.0 does not participate in lysis induced by other enzymes. The lyzing activity of this complex is associated with the carbohydrase enzymes that are at least three in number. Various carbohydrases may exert a synergistic effect upon their combined action on the protein-vitamin concentrate.", "contents": "[Study of the yeast dissolving enzymic complex by isoelectric focusing]. By isoelectric focussing the lyzing complex produced by Actinomyces griseinus-11 has been fractionated. The sole neutral protease which is active at pH 7.0 does not participate in lysis induced by other enzymes. The lyzing activity of this complex is associated with the carbohydrase enzymes that are at least three in number. Various carbohydrases may exert a synergistic effect upon their combined action on the protein-vitamin concentrate."}
{"id": "PMID:1724", "title": "[Isolation and basic properties of thiamine pyrophosphokinase from brewing yeast].", "content": "Thiamine pyrophosphokinase (EC 2.7.7.2) isolated from dry brewing yeast has been purified 20-fold with a 70% yield. Certain properties of the enzyme have been determined: pH and temperature optima, donor and acceptor concentrations, and relationship between the rate of cocarboxylase biosynthesis and the incubation time and the enzyme quantity. The effects of concentrations of bivalent metal ions Co2+, Mg2+ and Mn2+ on the rate of the enzymic reaction has been studied. A change in the pH optimum as a function of the nature of the ion-activator has been investigated. It has been shown that neopyrithiamin is a competitive inhibitor and oxythiamin inhibits the enzymic reaction insignificantly. Thiamine phosphate cannot be transformed into thiamine diphosphate by the purified enzyme.", "contents": "[Isolation and basic properties of thiamine pyrophosphokinase from brewing yeast]. Thiamine pyrophosphokinase (EC 2.7.7.2) isolated from dry brewing yeast has been purified 20-fold with a 70% yield. Certain properties of the enzyme have been determined: pH and temperature optima, donor and acceptor concentrations, and relationship between the rate of cocarboxylase biosynthesis and the incubation time and the enzyme quantity. The effects of concentrations of bivalent metal ions Co2+, Mg2+ and Mn2+ on the rate of the enzymic reaction has been studied. A change in the pH optimum as a function of the nature of the ion-activator has been investigated. It has been shown that neopyrithiamin is a competitive inhibitor and oxythiamin inhibits the enzymic reaction insignificantly. Thiamine phosphate cannot be transformed into thiamine diphosphate by the purified enzyme."}
{"id": "PMID:1725", "title": "[Trypsin interaction with sodium alginate].", "content": "The formation of an insoluble product of the interaction of trypsin and sodium alginate at pH 3-9 was studied. The optic density of the system was in an extreme relation to the composition. The insoluble phase was enriched in trypsin. The dispersion phase formed as a result of the electrostatic interaction between alginate macroanion and trypsin macrocation. The interaction brought about the formation of ATn, where n=90-900 (with an accuracy of the term Mw/Mn of alginate). The relation between the composition of the complex and pH was nonmonotonous.", "contents": "[Trypsin interaction with sodium alginate]. The formation of an insoluble product of the interaction of trypsin and sodium alginate at pH 3-9 was studied. The optic density of the system was in an extreme relation to the composition. The insoluble phase was enriched in trypsin. The dispersion phase formed as a result of the electrostatic interaction between alginate macroanion and trypsin macrocation. The interaction brought about the formation of ATn, where n=90-900 (with an accuracy of the term Mw/Mn of alginate). The relation between the composition of the complex and pH was nonmonotonous."}
{"id": "PMID:1726", "title": "[Study of properties of heat activated enzyme preparations].", "content": "The paper describes studies of heat treatment of the preparations amylorizin G10x, amylosubtilin G10x and glucoendomycopsin G15 and its effect on the relationshop between the rate of the enzymic reaction and the preparation concentration, optimal pH and temperatures, and the EDTA influence on the activity of heated preparations. After heating the preparations showed an elevation of optimal temperatures of their action and a shift of optimal pH to the alkaline region. Primary heating of the preparations resulted in an increase of the rate of the enzymic reaction. Heated preparations were less susceptible to the effect of the inhibitor that nonheated ones.", "contents": "[Study of properties of heat activated enzyme preparations]. The paper describes studies of heat treatment of the preparations amylorizin G10x, amylosubtilin G10x and glucoendomycopsin G15 and its effect on the relationshop between the rate of the enzymic reaction and the preparation concentration, optimal pH and temperatures, and the EDTA influence on the activity of heated preparations. After heating the preparations showed an elevation of optimal temperatures of their action and a shift of optimal pH to the alkaline region. Primary heating of the preparations resulted in an increase of the rate of the enzymic reaction. Heated preparations were less susceptible to the effect of the inhibitor that nonheated ones."}
{"id": "PMID:1727", "title": "[Effect of pH on the properties of the chemostatic culture of Canida utilis].", "content": "The effect of hydrogen and hydroxyl ions on the physiological features of the yeast C. utilis VKMU-1668 was studied. High acidity inhibited yeast growth and uncoupled pathways of the energy and constructive metabolism: normal respiration was disturbed and the electron transport chain was damaged in the site of cytochromes and not flavins. Hydroxyl ions also inhibited yeast growth and uncoupled pathways of the energy and constructive metabolism: oxygen uptake and the content of flavin adenone dinucleotide increased, dehydrogenase activity upon the use of glycerol decreased significantly, and the absolute amount of all cytochromes declined slightly. The chemical composition of cellular polymers at all pH values tested was stable enough. The amount of major metabolites--volatile oils and ketoacids--was insignificant.", "contents": "[Effect of pH on the properties of the chemostatic culture of Canida utilis]. The effect of hydrogen and hydroxyl ions on the physiological features of the yeast C. utilis VKMU-1668 was studied. High acidity inhibited yeast growth and uncoupled pathways of the energy and constructive metabolism: normal respiration was disturbed and the electron transport chain was damaged in the site of cytochromes and not flavins. Hydroxyl ions also inhibited yeast growth and uncoupled pathways of the energy and constructive metabolism: oxygen uptake and the content of flavin adenone dinucleotide increased, dehydrogenase activity upon the use of glycerol decreased significantly, and the absolute amount of all cytochromes declined slightly. The chemical composition of cellular polymers at all pH values tested was stable enough. The amount of major metabolites--volatile oils and ketoacids--was insignificant."}
{"id": "PMID:1729", "title": "[Activation of L-amino acids by aminoacyl-tRNA-synthetases from yeast Candida utilis IBPM-405].", "content": "The procedure for isolating aminoacyl-tRNA-synthetases from yeast Candida utilis IBPM-405 was developed. The rate of activation of L-amino acids in the formation of hydroxamates was different. Aspartic acid, asparagine, glutamic acid, tryptophane, phenyl alanine and methionine underwent the highest activation. The activation of alanine, arginine, hydroxyproline, serine and isoleucine was insignificant. Using aspartic acid, it was shown that the hydroxamate formation was ATP-stimulated and that the amount of hydroxamate increased with a rise of the protein concentration in the mixture to 9-10 mg/ml. The hydroxamate formation was inhibited by p-chloromercury-benzoate and heavy metal ions. Yeast aminoacyl-tRNA-synthetases showed L-aspartic and L-glutamic activities that were independent from Mg++ ions and ATP.", "contents": "[Activation of L-amino acids by aminoacyl-tRNA-synthetases from yeast Candida utilis IBPM-405]. The procedure for isolating aminoacyl-tRNA-synthetases from yeast Candida utilis IBPM-405 was developed. The rate of activation of L-amino acids in the formation of hydroxamates was different. Aspartic acid, asparagine, glutamic acid, tryptophane, phenyl alanine and methionine underwent the highest activation. The activation of alanine, arginine, hydroxyproline, serine and isoleucine was insignificant. Using aspartic acid, it was shown that the hydroxamate formation was ATP-stimulated and that the amount of hydroxamate increased with a rise of the protein concentration in the mixture to 9-10 mg/ml. The hydroxamate formation was inhibited by p-chloromercury-benzoate and heavy metal ions. Yeast aminoacyl-tRNA-synthetases showed L-aspartic and L-glutamic activities that were independent from Mg++ ions and ATP."}
{"id": "PMID:1733", "title": "[Properties of immobilized trypsin and alpha-chymotrypsin and their use for purification of proteinase inhibitors from potatoes].", "content": "Immobilized trypsin and alpha-chymotrypsin were obtained as a result of the enzyme attachment to bromo-cyanogen activated cepharose. Proteolytic activity (substrate--casein) of immobilized trypsin and alpha-chymotrypsin was 18.7 and 9%, respectively and their esterase activity with methyl ester benzoyl-L-arginine (trypsin) and ethyl ester acetyl-L-tyrosine (alpha-chymotrypsin) was 75 and 20% of that of soluble enzymes. Immobilized enzymes were used to purify proteinase inhibitors from potatoes by affine chromatography. Specific activity of trypsin and chymotrypsin inhibitors was increased 10 and 6 times, respectively. By isoelectric focussing it was shown that the purified preparation of chymotrypsin inhibitors consisted of two acid proteins and one alkaline protein, the latter being in predominance. The purified preparation of trypsin inhibitors contained equal amounts of proteins with the isoelectric point at pH 7.1 and 8.9 and a low quantity of the component with the isoelectric point at pH 5.7.", "contents": "[Properties of immobilized trypsin and alpha-chymotrypsin and their use for purification of proteinase inhibitors from potatoes]. Immobilized trypsin and alpha-chymotrypsin were obtained as a result of the enzyme attachment to bromo-cyanogen activated cepharose. Proteolytic activity (substrate--casein) of immobilized trypsin and alpha-chymotrypsin was 18.7 and 9%, respectively and their esterase activity with methyl ester benzoyl-L-arginine (trypsin) and ethyl ester acetyl-L-tyrosine (alpha-chymotrypsin) was 75 and 20% of that of soluble enzymes. Immobilized enzymes were used to purify proteinase inhibitors from potatoes by affine chromatography. Specific activity of trypsin and chymotrypsin inhibitors was increased 10 and 6 times, respectively. By isoelectric focussing it was shown that the purified preparation of chymotrypsin inhibitors consisted of two acid proteins and one alkaline protein, the latter being in predominance. The purified preparation of trypsin inhibitors contained equal amounts of proteins with the isoelectric point at pH 7.1 and 8.9 and a low quantity of the component with the isoelectric point at pH 5.7."}
{"id": "PMID:1731", "title": "[Some properties of proteases of the mould Mucor pusillus-917].", "content": "The proteolytic preparation of Mucor pusillus-917 has been obtained. The preparation produces an effective hydrolytic influence on milk casein. Thermal and acid inactivation of the proteolytic complex is the reaction of the first order. The activity-pH curves, calculations of ionization heat, inactivation of proteases by photooxidation and monoiodoacetic acid suggest that imidazole, carboxyl and sulphydryl groups of proteases are involved in the clotting and hydrolysis of milk.", "contents": "[Some properties of proteases of the mould Mucor pusillus-917]. The proteolytic preparation of Mucor pusillus-917 has been obtained. The preparation produces an effective hydrolytic influence on milk casein. Thermal and acid inactivation of the proteolytic complex is the reaction of the first order. The activity-pH curves, calculations of ionization heat, inactivation of proteases by photooxidation and monoiodoacetic acid suggest that imidazole, carboxyl and sulphydryl groups of proteases are involved in the clotting and hydrolysis of milk."}
{"id": "PMID:1737", "title": "[Effect of different pH values on the activity and quaternary structure of asparaginase in Escherichia coli extracts].", "content": "The effect of low pH values on the activity and stability of the quaternary structure of asparaginase from Escherichia coli was investigated at early stages of purification of the enzyme. Acidification of the E. coli extract was most effective before the biomass separation. This procedure helped to separate biomass together with coagulated ballast proteins and not to reduce the activity. Upon storage of the acidified solution at 5 degrees C reversible dissociation of the tetrametric structure into dimers and monomers occurred. Stability of L-asparaginase in the storage of acetone powders and during extraction was studied. It is suggested that asparaginase in bacterial cells in unlikely to have the quaternary structure which normally occurs in the solution at neutral pH.", "contents": "[Effect of different pH values on the activity and quaternary structure of asparaginase in Escherichia coli extracts]. The effect of low pH values on the activity and stability of the quaternary structure of asparaginase from Escherichia coli was investigated at early stages of purification of the enzyme. Acidification of the E. coli extract was most effective before the biomass separation. This procedure helped to separate biomass together with coagulated ballast proteins and not to reduce the activity. Upon storage of the acidified solution at 5 degrees C reversible dissociation of the tetrametric structure into dimers and monomers occurred. Stability of L-asparaginase in the storage of acetone powders and during extraction was studied. It is suggested that asparaginase in bacterial cells in unlikely to have the quaternary structure which normally occurs in the solution at neutral pH."}
{"id": "PMID:1739", "title": "[Preparation of proteolytic enzymes from the thermophilous actinomycete Actinomyces thermovulgaris str. T-54].", "content": "A preparation with a high proteolytic activity has been obtained by acetone precipitation from the culture liquid filtrate of the thermophilous actinomycete Actinomyces thermovulgaris str. T-54. The proteolytic (caseinolytic), fibrinolytic and thrombolytic activity of the preparation is comparable with that of trypsin and far superior to that of fibrinolysine. The preparation is stable at pH 5.0=9.5 and inactivated in the acid zone. The study of pH dependent proteolytic activity has shown acid, neutral and alkaline proteases in the preparation. It is relatively thermostable, and is completely inactivated for 10 min at 90 degrees. It is suggested that the preparation contains four enzymes or four enzymic groups that are different in their temperature sensitivity.", "contents": "[Preparation of proteolytic enzymes from the thermophilous actinomycete Actinomyces thermovulgaris str. T-54]. A preparation with a high proteolytic activity has been obtained by acetone precipitation from the culture liquid filtrate of the thermophilous actinomycete Actinomyces thermovulgaris str. T-54. The proteolytic (caseinolytic), fibrinolytic and thrombolytic activity of the preparation is comparable with that of trypsin and far superior to that of fibrinolysine. The preparation is stable at pH 5.0=9.5 and inactivated in the acid zone. The study of pH dependent proteolytic activity has shown acid, neutral and alkaline proteases in the preparation. It is relatively thermostable, and is completely inactivated for 10 min at 90 degrees. It is suggested that the preparation contains four enzymes or four enzymic groups that are different in their temperature sensitivity."}
{"id": "PMID:1735", "title": "[Regulation of glutamine synthetase of the fodder yeast Candida tropicalis by ammonium ions].", "content": "The effect of ammonium on glutamine synthetase of fodder yeast Candida tropicalis was studied. Ammonium ions were found to repress the synthesis of glutamine synthetase of fodder yeast and to inhibit the enzyme in the cells. The substitution of glutamic acid for ammonium in the nutrient medium brought about depression of glutamine synthetase.", "contents": "[Regulation of glutamine synthetase of the fodder yeast Candida tropicalis by ammonium ions]. The effect of ammonium on glutamine synthetase of fodder yeast Candida tropicalis was studied. Ammonium ions were found to repress the synthesis of glutamine synthetase of fodder yeast and to inhibit the enzyme in the cells. The substitution of glutamic acid for ammonium in the nutrient medium brought about depression of glutamine synthetase."}
{"id": "PMID:1738", "title": "[Rhizopus microsporus strain UzLT-I--a thermotolerant producer of lipase].", "content": "The properties of the thermotolerant fungus Rhizopus microsporus strain UzLT-1--producer of lipolyptic enzymes are described. Optimal cultivation conditions--40 degrees, C, pH 4.5--Are determined. The lipolytic activity of the culture on the medium consisting of corn extract (2%), cotton-seed oil (1%) and water is 850 ml 0.1 n KOH per 100 ml culture liquid. The enzymic preparations of lipase have been precipitated by isopropanol and ammonium sulphate. The preparation precipitated by isopropanol shows its macimum activity at pH 4.2 and 7.8 and a temperature of 40--50 degrees C.", "contents": "[Rhizopus microsporus strain UzLT-I--a thermotolerant producer of lipase]. The properties of the thermotolerant fungus Rhizopus microsporus strain UzLT-1--producer of lipolyptic enzymes are described. Optimal cultivation conditions--40 degrees, C, pH 4.5--Are determined. The lipolytic activity of the culture on the medium consisting of corn extract (2%), cotton-seed oil (1%) and water is 850 ml 0.1 n KOH per 100 ml culture liquid. The enzymic preparations of lipase have been precipitated by isopropanol and ammonium sulphate. The preparation precipitated by isopropanol shows its macimum activity at pH 4.2 and 7.8 and a temperature of 40--50 degrees C."}
{"id": "PMID:1736", "title": "[Effect of the composition of the nutrient medium on the synthesis of acid-fast alpha-amylase by different strains of Aspergillus].", "content": "The capacity of 86 strains of the Aspergillus fungus to synthesize acid stable alpha-amylase was examined. The strains of Asp. niger showing a high capacity of synthesizing the enzyme were isolated. Repeated cultivation of the selected cultures on the Minoda agar medium led to a 200% increase in the enzyme activity in the submerged culture. Addition of sodium nitrate to the Minoda medium during submerged cultivation allowed a 3-fold increase of the synthesis of acid stable alpha-amylase.", "contents": "[Effect of the composition of the nutrient medium on the synthesis of acid-fast alpha-amylase by different strains of Aspergillus]. The capacity of 86 strains of the Aspergillus fungus to synthesize acid stable alpha-amylase was examined. The strains of Asp. niger showing a high capacity of synthesizing the enzyme were isolated. Repeated cultivation of the selected cultures on the Minoda agar medium led to a 200% increase in the enzyme activity in the submerged culture. Addition of sodium nitrate to the Minoda medium during submerged cultivation allowed a 3-fold increase of the synthesis of acid stable alpha-amylase."}
{"id": "PMID:1740", "title": "[Analysis of acid proteinases from Aspergillus terricola].", "content": "The specific action and composition of the functional groups of active centres of three fractions of acid proteinases from Aspergillus terricola have been studied. With respect to the hydrolysis rates of acetyl-L-phenylalanyl-L-tyrosine and carbobenzoxy-D, L-glycyl-phenylalanine by the three fractions it is suggested that the interaction of acid proteinases with the substrate involves hydrophobic forces. It has been shown that the above fractions are no metal enzymes. By means of the diazocarbonyl inhibitor an occurrence of a catalytically active carboxy group has been found in the active centre of proteinases. The proteinase inhibition by Fe3+ in the presence of citric acid is an indirect evidence of the existence of several carboxy groups and, possibly, of a hydroxy group in the active centre of acid proteinases from Aspergillus terricola.", "contents": "[Analysis of acid proteinases from Aspergillus terricola]. The specific action and composition of the functional groups of active centres of three fractions of acid proteinases from Aspergillus terricola have been studied. With respect to the hydrolysis rates of acetyl-L-phenylalanyl-L-tyrosine and carbobenzoxy-D, L-glycyl-phenylalanine by the three fractions it is suggested that the interaction of acid proteinases with the substrate involves hydrophobic forces. It has been shown that the above fractions are no metal enzymes. By means of the diazocarbonyl inhibitor an occurrence of a catalytically active carboxy group has been found in the active centre of proteinases. The proteinase inhibition by Fe3+ in the presence of citric acid is an indirect evidence of the existence of several carboxy groups and, possibly, of a hydroxy group in the active centre of acid proteinases from Aspergillus terricola."}
{"id": "PMID:1741", "title": "[Thermo- and pH-stability of soluble and silichrome-80 immobilized proteinase from Bacillus subtilis].", "content": "The stability to heating and pH changing of two proteinases of Bacillus subtilis was studied. The preparations were: protosubtilin G10x with an activity of 21500 units/g and proteinase immobilized on silochrome C-80 with an activity of 3880 units/g. For protosubtilin G10x the pH optimum was 7.0-7.2. For the immobilized preparation 96-100% activity was found at pH 5.5-10.0. The difference between the two proteinase preparations was more distinct with respect to the temperature minimum. The initial preparation-protosubtilin G10x was more stable to low temperature and showed maximum activity at 40 degrees; the immobilized preparation was less active at low temperatures and showed maximum activity at 60-70 degrees. Protosubtilin G10x was more sensitive to pH changes, especially in the acid zone (pH 4.5). It was significantly activated at 30-40 degrees and was unstable at 50-60 degrees. The immobilized preparation was activated at 50- 60 degrees and was insensitive to pH changes in the range of 4.5 to 9.2 and temperature changes from 10 degrees to 40 degrees for 1.5-2.0 hours.", "contents": "[Thermo- and pH-stability of soluble and silichrome-80 immobilized proteinase from Bacillus subtilis]. The stability to heating and pH changing of two proteinases of Bacillus subtilis was studied. The preparations were: protosubtilin G10x with an activity of 21500 units/g and proteinase immobilized on silochrome C-80 with an activity of 3880 units/g. For protosubtilin G10x the pH optimum was 7.0-7.2. For the immobilized preparation 96-100% activity was found at pH 5.5-10.0. The difference between the two proteinase preparations was more distinct with respect to the temperature minimum. The initial preparation-protosubtilin G10x was more stable to low temperature and showed maximum activity at 40 degrees; the immobilized preparation was less active at low temperatures and showed maximum activity at 60-70 degrees. Protosubtilin G10x was more sensitive to pH changes, especially in the acid zone (pH 4.5). It was significantly activated at 30-40 degrees and was unstable at 50-60 degrees. The immobilized preparation was activated at 50- 60 degrees and was insensitive to pH changes in the range of 4.5 to 9.2 and temperature changes from 10 degrees to 40 degrees for 1.5-2.0 hours."}
{"id": "PMID:1744", "title": "Regulation of synthesis of glutamine synthetase by adenylylated glutamine synthetase.", "content": "We have examined three mutants of Klebsiella aerogenes whose genetic lesions (glnB, glnD, and glnE) are in loci unlinked to the structural gene for glutamine sythetase (glnA) and in which the control of both the level and state of adenylylation of glutamine synthetase is altered. Each mutation alters a different component of the adenylylation system of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. Inability of the cell to deadenylylate glutamine synthetase (glnB and glnD) greatly decreases its production, while inability to adenylylate glutamine sythetase (glnE) results in its constitutively high production. These results together with our previous results indicate that adenylylated glutamine synthetase inhibits the transcription of glnA.", "contents": "Regulation of synthesis of glutamine synthetase by adenylylated glutamine synthetase. We have examined three mutants of Klebsiella aerogenes whose genetic lesions (glnB, glnD, and glnE) are in loci unlinked to the structural gene for glutamine sythetase (glnA) and in which the control of both the level and state of adenylylation of glutamine synthetase is altered. Each mutation alters a different component of the adenylylation system of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. Inability of the cell to deadenylylate glutamine synthetase (glnB and glnD) greatly decreases its production, while inability to adenylylate glutamine sythetase (glnE) results in its constitutively high production. These results together with our previous results indicate that adenylylated glutamine synthetase inhibits the transcription of glnA."}
{"id": "PMID:1742", "title": "[Preparation and properties of beta-galactosidase linked covalently with KM-cellulose].", "content": "Fungal beta-galactosidase was immobilized by covalent binding with KM-cellulose. The resultant preparation contained 3 mg protein per 1 g carrier; its specific activity was 65% of the initial one. As a result of immobilization pH optimum remained unchanged whereas the temperature optimum decreased from 65 degrees to 50 degrees. The seemings Km of the immobilized enzyme varied insignificantly as compared with Km of the soluble enzyme.", "contents": "[Preparation and properties of beta-galactosidase linked covalently with KM-cellulose]. Fungal beta-galactosidase was immobilized by covalent binding with KM-cellulose. The resultant preparation contained 3 mg protein per 1 g carrier; its specific activity was 65% of the initial one. As a result of immobilization pH optimum remained unchanged whereas the temperature optimum decreased from 65 degrees to 50 degrees. The seemings Km of the immobilized enzyme varied insignificantly as compared with Km of the soluble enzyme."}
{"id": "PMID:1743", "title": "[Conditions for splitting protodioscine--the main glycoside from Tribulus terrestris L. by the enzymatic preparation from Aspergillus niger BKMt-33].", "content": "The conditions for splitting protodioscine--the main steroid saponine isolated from Tribulus terrestris L. by the enzymic preparation of Aspergillus niger str. BKMt-33 were investigated. The optimal conditions were found to be as follows: pH 4-5, temperature 30-37 degrees (the substrate concentration--5 mg%, concentration of the enzymic preparation--1%). Under these conditions the enzymolysis continued 24 hours. Mg+2 and K+ ions accelerated the reaction twice. As a result of the enzymic hydrolysis dioscine and trilline were obtained. This indicates beta-glucosidase and alpha-rhamnosidase activities of the enzymic complex isolated from Aspergillus niger str. BKMt-33.", "contents": "[Conditions for splitting protodioscine--the main glycoside from Tribulus terrestris L. by the enzymatic preparation from Aspergillus niger BKMt-33]. The conditions for splitting protodioscine--the main steroid saponine isolated from Tribulus terrestris L. by the enzymic preparation of Aspergillus niger str. BKMt-33 were investigated. The optimal conditions were found to be as follows: pH 4-5, temperature 30-37 degrees (the substrate concentration--5 mg%, concentration of the enzymic preparation--1%). Under these conditions the enzymolysis continued 24 hours. Mg+2 and K+ ions accelerated the reaction twice. As a result of the enzymic hydrolysis dioscine and trilline were obtained. This indicates beta-glucosidase and alpha-rhamnosidase activities of the enzymic complex isolated from Aspergillus niger str. BKMt-33."}
{"id": "PMID:1745", "title": "Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells.", "content": "Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal cells from embryonic mouse sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high tyrosine 3-monooxygenase activity and synthesizes dopamine. These cells also have excitable membranes and generate action potentials in response to electrical stimuli. Thus hybrid cells, generated by fusion of neuroblastoma cells with normal cells from the nervous system, can acquire neural properties not found with the parental neuroblastoma cells.", "contents": "Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells. Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal cells from embryonic mouse sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high tyrosine 3-monooxygenase activity and synthesizes dopamine. These cells also have excitable membranes and generate action potentials in response to electrical stimuli. Thus hybrid cells, generated by fusion of neuroblastoma cells with normal cells from the nervous system, can acquire neural properties not found with the parental neuroblastoma cells."}
{"id": "PMID:1746", "title": "Regulation of ferredoxin-catalyzed photosynthetic phosphorylations.", "content": "Under aerobic conditions that are likely to prevail in chloroplasts in vivo, the optimal concentration of ferredoxin for cyclic photophosphorylation was found to be equal to that required for NADP reduction and about one-tenth of that needed for cyclic photophosphorylation under anaerobic conditions. In the presence of ferredoxin and NADP, cyclic photophosphorylation operated concurrently with noncyclic photophosphorylation, producing an ATP: NADPH ratio of about 1.5. The effective operation of ferredoxin-catalyzed cyclic photophosphorylation by itself required a curtailment of the electron flow from water which was accomplished experimentally by the use of either an inhibitor or far-red monochromatic light. An unexpected discovery was that the operation of cyclic photophosphorylation by itself was also regulated by a back reaction of NADPH and ferredoxin with two components of chloroplast membranes, component C550 and cytochrome b559. The significance of these findings to photosynthesis in vivo is discussed.", "contents": "Regulation of ferredoxin-catalyzed photosynthetic phosphorylations. Under aerobic conditions that are likely to prevail in chloroplasts in vivo, the optimal concentration of ferredoxin for cyclic photophosphorylation was found to be equal to that required for NADP reduction and about one-tenth of that needed for cyclic photophosphorylation under anaerobic conditions. In the presence of ferredoxin and NADP, cyclic photophosphorylation operated concurrently with noncyclic photophosphorylation, producing an ATP: NADPH ratio of about 1.5. The effective operation of ferredoxin-catalyzed cyclic photophosphorylation by itself required a curtailment of the electron flow from water which was accomplished experimentally by the use of either an inhibitor or far-red monochromatic light. An unexpected discovery was that the operation of cyclic photophosphorylation by itself was also regulated by a back reaction of NADPH and ferredoxin with two components of chloroplast membranes, component C550 and cytochrome b559. The significance of these findings to photosynthesis in vivo is discussed."}
{"id": "PMID:1747", "title": "High resolution 31P nuclear magnetic resonance studies of intact yeast cells.", "content": "High resolution 31P nuclear magnetic resonance (NMR) spectra at 145.7 MHZ are presented for intact yeast cells. Several peaks are resolved and assigned. They include the middle phosphate peaks from long chain or cyclic polyphosphates. Our results are consistent with the suggestion that these polyphosphates act as a phosphate store in the cell. We have also been able to measure cytoplasmic pH using the orthophosphate peak inside the cell, as compared with outside the cell. The results show that yeast cells maintain their cytoplasmic pH around 6.3. This value is considerably higher than the acidic extracellular pH at which they normally live. These preliminary results indicate that 31P NMR at 145.7 MHZ can be a rapid, informative, and non-invasive method for probing biochemical events within living cells.", "contents": "High resolution 31P nuclear magnetic resonance studies of intact yeast cells. High resolution 31P nuclear magnetic resonance (NMR) spectra at 145.7 MHZ are presented for intact yeast cells. Several peaks are resolved and assigned. They include the middle phosphate peaks from long chain or cyclic polyphosphates. Our results are consistent with the suggestion that these polyphosphates act as a phosphate store in the cell. We have also been able to measure cytoplasmic pH using the orthophosphate peak inside the cell, as compared with outside the cell. The results show that yeast cells maintain their cytoplasmic pH around 6.3. This value is considerably higher than the acidic extracellular pH at which they normally live. These preliminary results indicate that 31P NMR at 145.7 MHZ can be a rapid, informative, and non-invasive method for probing biochemical events within living cells."}
{"id": "PMID:1748", "title": "Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture.", "content": "Stimulation with phytohemagglutinin of the leukocytes from six of the seven known individuals with UDP-galactose 4-epimerase (= UDP-glucose 4-epimerase; EC 5.1.3.2) deficiency consistently resulted in the appearance of epimerase activity in the cultured cells. A long-term lymphoblast culture derived from one proband also contained an active epimerase enzyme. A comparison of the properties of this enzyme with those of epimerase produced by control lymphoblast lines revealed comparable Km values for UDP-galactose and NAD and identical behavior on polyacrylamide electrophoresis. However, a difference in the NAD requirement for heat stability at 40 degree provided some evidence for a structural defect in this enzyme. Possible explanations for the appearance of UDP-galactose 4-epimerase activity in stimulated lymphocytes include an increased rate of synthesis of a mutant enzyme and a derepression of an epimerase locus during lymphocyte transformation.", "contents": "Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture. Stimulation with phytohemagglutinin of the leukocytes from six of the seven known individuals with UDP-galactose 4-epimerase (= UDP-glucose 4-epimerase; EC 5.1.3.2) deficiency consistently resulted in the appearance of epimerase activity in the cultured cells. A long-term lymphoblast culture derived from one proband also contained an active epimerase enzyme. A comparison of the properties of this enzyme with those of epimerase produced by control lymphoblast lines revealed comparable Km values for UDP-galactose and NAD and identical behavior on polyacrylamide electrophoresis. However, a difference in the NAD requirement for heat stability at 40 degree provided some evidence for a structural defect in this enzyme. Possible explanations for the appearance of UDP-galactose 4-epimerase activity in stimulated lymphocytes include an increased rate of synthesis of a mutant enzyme and a derepression of an epimerase locus during lymphocyte transformation."}
{"id": "PMID:1749", "title": "beta-Bungarotoxin, a pre-synaptic toxin with enzymatic activity.", "content": "beta-Bungarotoxin, a pre-synaptic neurotoxin isolated from the venom of the snake Bungarus multicinctus, has been shown to modify release of neurotransmitter at the neuromuscular junction. In this communication, we demonstrate that beta-bungarotoxin is a potent phospholipase A2 (phosphatide 2-acyl hydrolase, EC 3.1.1.4), comparable in activity with purified phospholipase enzymes from Naja naja and Vipera russellii. The phospholipase activity of beta-bungarotoxin requires calcium and is stimulated by deoxycholate. When strontium replaces calcium, no phospholipase activity is detected. Since neuromuscular transmission is not blocked when calcium is replaced by strontium, it was possible to examine the effects of the toxin on neuromuscular transmission in the presence of strontium. Under these conditions, when the phospholipase activity should be inhibited, the toxin has little or no effect on neuromuscular transmission. If beta-bungarotoxin owes its toxicity in part to its enzymatic activity, then it must be placed in a different class from those toxins which produce their effect by binding passively to an appropriate receptor.", "contents": "beta-Bungarotoxin, a pre-synaptic toxin with enzymatic activity. beta-Bungarotoxin, a pre-synaptic neurotoxin isolated from the venom of the snake Bungarus multicinctus, has been shown to modify release of neurotransmitter at the neuromuscular junction. In this communication, we demonstrate that beta-bungarotoxin is a potent phospholipase A2 (phosphatide 2-acyl hydrolase, EC 3.1.1.4), comparable in activity with purified phospholipase enzymes from Naja naja and Vipera russellii. The phospholipase activity of beta-bungarotoxin requires calcium and is stimulated by deoxycholate. When strontium replaces calcium, no phospholipase activity is detected. Since neuromuscular transmission is not blocked when calcium is replaced by strontium, it was possible to examine the effects of the toxin on neuromuscular transmission in the presence of strontium. Under these conditions, when the phospholipase activity should be inhibited, the toxin has little or no effect on neuromuscular transmission. If beta-bungarotoxin owes its toxicity in part to its enzymatic activity, then it must be placed in a different class from those toxins which produce their effect by binding passively to an appropriate receptor."}
{"id": "PMID:1750", "title": "Isolation and characterization of an unsaturated fatty acid-requiring mutant of cultured mammalian cells.", "content": "An unsaturated fatty acid-requiring mutant derived from Chinese hamster ovary (CHO) cells has been isolated and characterized. This mutant grows normally when oleate or other unsaturated fatty acids are supplemented in the growth medium. Unlike the wild-type CHO cells, growth stops when medium is deprived of unsaturated fatty acid. Whole cell pulse experiments with [14C]acetate or [14C]stearate indicate that the mutant is defective in unsaturated fatty acid synthesis. Enzyme assays in vitro show that the enzymatic defect of the mutant is localized to the microsomal stearoyl-CoA desaturase.", "contents": "Isolation and characterization of an unsaturated fatty acid-requiring mutant of cultured mammalian cells. An unsaturated fatty acid-requiring mutant derived from Chinese hamster ovary (CHO) cells has been isolated and characterized. This mutant grows normally when oleate or other unsaturated fatty acids are supplemented in the growth medium. Unlike the wild-type CHO cells, growth stops when medium is deprived of unsaturated fatty acid. Whole cell pulse experiments with [14C]acetate or [14C]stearate indicate that the mutant is defective in unsaturated fatty acid synthesis. Enzyme assays in vitro show that the enzymatic defect of the mutant is localized to the microsomal stearoyl-CoA desaturase."}
{"id": "PMID:1751", "title": "DNA single-strand breaks during repair of UV damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum.", "content": "The method of DNA alkaline elution was applied to a study of the formation and resealing of DNA single-strand breaks after irradiation of human fibroblasts with ultraviolet light (UV). The general features of the results were consistent with current concepts of DNA excision repair, in that breaks appeared rapidly after UV, and resealed slowly in normal fibroblasts, whereas breaks did not appear in those cells of patients with xeroderma pigmentosum (XP) that are known to have defects in DNA repair synthesis. The appearance of breaks required a short post-UV incubation, consistent with the expected action of an endonuclease. Cells of the variant form of XP characterized by normal DNA repair synthesis exhibited normal production of breaks after UV, but were slower than normal cells in resealing these breaks. This difference was enhanced by caffeine. A model is proposed to relate this finding with a previously described defect in post-replication repair in these XP variant cells. DNA crosslinking appears to cause an underestimate in the measurement of DNA breakage after UV.", "contents": "DNA single-strand breaks during repair of UV damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum. The method of DNA alkaline elution was applied to a study of the formation and resealing of DNA single-strand breaks after irradiation of human fibroblasts with ultraviolet light (UV). The general features of the results were consistent with current concepts of DNA excision repair, in that breaks appeared rapidly after UV, and resealed slowly in normal fibroblasts, whereas breaks did not appear in those cells of patients with xeroderma pigmentosum (XP) that are known to have defects in DNA repair synthesis. The appearance of breaks required a short post-UV incubation, consistent with the expected action of an endonuclease. Cells of the variant form of XP characterized by normal DNA repair synthesis exhibited normal production of breaks after UV, but were slower than normal cells in resealing these breaks. This difference was enhanced by caffeine. A model is proposed to relate this finding with a previously described defect in post-replication repair in these XP variant cells. DNA crosslinking appears to cause an underestimate in the measurement of DNA breakage after UV."}
{"id": "PMID:1752", "title": "Modifications of purified glucose-6-phosphate dehydrogenase and other enzymes by a factor of low molecular weight abundant in some leukemic cells.", "content": "Highly purified platelet glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate:NADP+ 1-oxidoreductase, EC 1.1.1.49) can be modified in its isoelectric point and its molecular specific activity by extracts of some leukemic granulocytes. The \"G6PD modifying factors\" are relatively small molecules (molecular weight slightly under 5000), thermostable, dialyzable, and ultrafilterable. These molecules are destroyed by various endo- and exopeptidases and by serine enzymes present in crude extracts of leukocytes and commercial preparations of ribonuclease. The alterations of platelet G6PD due to the \"G6PD modifying factors\" are stable and not reversible by dialysis or further chromatography. The leukemic extracts which are able to modify G6PD also can modify the electrophoretic mobility and (or) the enzymatic activity of purified leukocyte pyruvate kinase, 6-phosphogluconate dehydrogenase, and glucosephosphate isomerase. The chemical nature of such modifications and their relationships with post-translational modifications which occur in leukemic or normal cells are discussed.", "contents": "Modifications of purified glucose-6-phosphate dehydrogenase and other enzymes by a factor of low molecular weight abundant in some leukemic cells. Highly purified platelet glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate:NADP+ 1-oxidoreductase, EC 1.1.1.49) can be modified in its isoelectric point and its molecular specific activity by extracts of some leukemic granulocytes. The \"G6PD modifying factors\" are relatively small molecules (molecular weight slightly under 5000), thermostable, dialyzable, and ultrafilterable. These molecules are destroyed by various endo- and exopeptidases and by serine enzymes present in crude extracts of leukocytes and commercial preparations of ribonuclease. The alterations of platelet G6PD due to the \"G6PD modifying factors\" are stable and not reversible by dialysis or further chromatography. The leukemic extracts which are able to modify G6PD also can modify the electrophoretic mobility and (or) the enzymatic activity of purified leukocyte pyruvate kinase, 6-phosphogluconate dehydrogenase, and glucosephosphate isomerase. The chemical nature of such modifications and their relationships with post-translational modifications which occur in leukemic or normal cells are discussed."}
{"id": "PMID:1753", "title": "Copper-induced activation of aortic lysyl oxidase in vivo.", "content": "Raising day-old chicks on diets lacking copper severely depressed the activity of lysyl oxidase, a copper metalloenzyme in connective tissue. Administration of CuSO4 either through the diet or through intraperitoneal injections restored the lysyl oxidase activity in aortic tissue. Two hours after the chicks received CuSO4 (1 mg/kg) the activity of lysyl oxidase rose rapidly to attain, within 4-6 hr, a new steady-state level which was five to 20 times higher than the basal (saline-injected) activity. Twenty hours after copper administration, activity was still higher, in some experiments double that achieved at 6 hr. Very low amounts of cycloheximide injected intraperitoneally 45 min before and 3 hr after copper suppressed the activation response by two-thirds. Cycloheximide given 2 or 4 hr after the copper was only one-half as effective. Actinomycin D caused only a 10-15% inhibition of the copper-induced activation. The data suggest that copper is a key regulator of lysyl oxidase activity in aorta and may in fact be a major determinant of the steady-state levels of the enzyme in that tissue.", "contents": "Copper-induced activation of aortic lysyl oxidase in vivo. Raising day-old chicks on diets lacking copper severely depressed the activity of lysyl oxidase, a copper metalloenzyme in connective tissue. Administration of CuSO4 either through the diet or through intraperitoneal injections restored the lysyl oxidase activity in aortic tissue. Two hours after the chicks received CuSO4 (1 mg/kg) the activity of lysyl oxidase rose rapidly to attain, within 4-6 hr, a new steady-state level which was five to 20 times higher than the basal (saline-injected) activity. Twenty hours after copper administration, activity was still higher, in some experiments double that achieved at 6 hr. Very low amounts of cycloheximide injected intraperitoneally 45 min before and 3 hr after copper suppressed the activation response by two-thirds. Cycloheximide given 2 or 4 hr after the copper was only one-half as effective. Actinomycin D caused only a 10-15% inhibition of the copper-induced activation. The data suggest that copper is a key regulator of lysyl oxidase activity in aorta and may in fact be a major determinant of the steady-state levels of the enzyme in that tissue."}
{"id": "PMID:1754", "title": "Evidence that acyl coenzyme A synthetase activity is required for repression of yeast acetyl coenzyme A carboxylase by exogenous fatty acids.", "content": "The cellular content of acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] in Saccharomyces cerevisiae is reduced by the addition of long-chain fatty acids to the culture medium. Mutant strains of S. cerevisiae defective in acyl-CoA synthetase [acid:CoA ligase (AMP-forming), EC 6.2.1.3] were isolated and used to determine whether fatty acid itself or a metabolite of fatty acid is more directly responsible for the repression of acetyl-CoA carboxylase. Cells of the mutant strains were capable of incorporating fatty acid to an extent comparable to that observed with the wild-type strain, but they accumulated markedly more of the incorporated fatty acid in the nonesterified form than did the wild-type cells. The level of acetyl-CoA carboxylase activity in the mutants, in contrast to that in the wild-type strain, was hardly affected by the addition of fatty acids to the medium. These results indicate that the activation of exogenous fatty acid is required for the repression of acetyl-CoA carboxylase, supporting the view that the repressive effect is mediated by some compound metabolically derived from fatty acid.", "contents": "Evidence that acyl coenzyme A synthetase activity is required for repression of yeast acetyl coenzyme A carboxylase by exogenous fatty acids. The cellular content of acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] in Saccharomyces cerevisiae is reduced by the addition of long-chain fatty acids to the culture medium. Mutant strains of S. cerevisiae defective in acyl-CoA synthetase [acid:CoA ligase (AMP-forming), EC 6.2.1.3] were isolated and used to determine whether fatty acid itself or a metabolite of fatty acid is more directly responsible for the repression of acetyl-CoA carboxylase. Cells of the mutant strains were capable of incorporating fatty acid to an extent comparable to that observed with the wild-type strain, but they accumulated markedly more of the incorporated fatty acid in the nonesterified form than did the wild-type cells. The level of acetyl-CoA carboxylase activity in the mutants, in contrast to that in the wild-type strain, was hardly affected by the addition of fatty acids to the medium. These results indicate that the activation of exogenous fatty acid is required for the repression of acetyl-CoA carboxylase, supporting the view that the repressive effect is mediated by some compound metabolically derived from fatty acid."}
{"id": "PMID:1755", "title": "Glutathione and gamma-glutamyl cycle enzymes in crypt and villus tip cells of rat jejunal mucosa.", "content": "Villus tip cells and crypt cells of rat jejunal mucosa were separated by the planning procedure of Imondi et al. and were studied with respect to their activities of the enzymes of the gamma-glutamyl cycle and glutathione content. The villus tip cells exhibit much higher gamma-glutamyl transpeptidase activities than do the crypt cells: thus, gamma-glutamyl trnaspeptidase appears to be a villus-specific enzyme. gamma-Glutamyl cyclotransferase and the enzymes required for glutathione synthesis are not specifically localized to either the crypt or villus tip cells but are present in both. The crypt cells have a high concentration of glutathione (4-5 mM) comparable to the levels found in liver and kidney; in contrast, the villus tip cells have much lower concentrations. On fasting, the glutathione concentration decreased markedly in both villus tip and crypt cells; feeding of protein, but not of sucrose, led to increased glutathione concentrations. The migration of cells from the undifferentiated crypt cell region to the villus tip is associated with structural and biochemical changes that equip the cell for its mature functional activities, which include transport. The present findings indicate that such cellular differentiation and migration is associated with a marked increase in gamma-glutamyl transpeptidase activity and in the utilization of glutathione.", "contents": "Glutathione and gamma-glutamyl cycle enzymes in crypt and villus tip cells of rat jejunal mucosa. Villus tip cells and crypt cells of rat jejunal mucosa were separated by the planning procedure of Imondi et al. and were studied with respect to their activities of the enzymes of the gamma-glutamyl cycle and glutathione content. The villus tip cells exhibit much higher gamma-glutamyl transpeptidase activities than do the crypt cells: thus, gamma-glutamyl trnaspeptidase appears to be a villus-specific enzyme. gamma-Glutamyl cyclotransferase and the enzymes required for glutathione synthesis are not specifically localized to either the crypt or villus tip cells but are present in both. The crypt cells have a high concentration of glutathione (4-5 mM) comparable to the levels found in liver and kidney; in contrast, the villus tip cells have much lower concentrations. On fasting, the glutathione concentration decreased markedly in both villus tip and crypt cells; feeding of protein, but not of sucrose, led to increased glutathione concentrations. The migration of cells from the undifferentiated crypt cell region to the villus tip is associated with structural and biochemical changes that equip the cell for its mature functional activities, which include transport. The present findings indicate that such cellular differentiation and migration is associated with a marked increase in gamma-glutamyl transpeptidase activity and in the utilization of glutathione."}
{"id": "PMID:1756", "title": "Maturation of neuroblastoma cells in the presence of dimethylsulfoxide.", "content": "Addition of dimethylsulfoxide at concentrations of 1% and 2% (vol/vol) to cells of mouse neuroblastoma clone NIE-115 in the confluent phase of growth resulted in the production of morphologically differentiated cultures with extensive process formation. Cell maintained in 2% dimethylsulfoxide remained in a stable nondividing condition for periods of up to 4 weeks. A high degree of electrical excitability was found in these cells, but there was no clear correlation of this property with the level of induction of either acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) or tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2]. In addition, intracellular levels of cyclic 3':5'-AMP were not elevated in fully morphologically and electrically differentiated cells. While cell division was markedly inhibited by 2% or higher concentrations of dimethylsulfoxide, at 1% growth continued at a somewhat slowed rate and such cultures exhibited enhanced process formation and electrical activity for a relatively short period. High concentrations (3% or 4%) of dimethylsulfoxide totally suppressed process formation and did not result in increased excitability, but cells maintained high resting potentials. The results suggest that the development of the excitable membrane in neuroblastoma cells may be expressed independently of neurospecific enzyme induction, and does not require a sustained elevation of cyclic 3':5'-AMP levels.", "contents": "Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. Addition of dimethylsulfoxide at concentrations of 1% and 2% (vol/vol) to cells of mouse neuroblastoma clone NIE-115 in the confluent phase of growth resulted in the production of morphologically differentiated cultures with extensive process formation. Cell maintained in 2% dimethylsulfoxide remained in a stable nondividing condition for periods of up to 4 weeks. A high degree of electrical excitability was found in these cells, but there was no clear correlation of this property with the level of induction of either acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) or tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2]. In addition, intracellular levels of cyclic 3':5'-AMP were not elevated in fully morphologically and electrically differentiated cells. While cell division was markedly inhibited by 2% or higher concentrations of dimethylsulfoxide, at 1% growth continued at a somewhat slowed rate and such cultures exhibited enhanced process formation and electrical activity for a relatively short period. High concentrations (3% or 4%) of dimethylsulfoxide totally suppressed process formation and did not result in increased excitability, but cells maintained high resting potentials. The results suggest that the development of the excitable membrane in neuroblastoma cells may be expressed independently of neurospecific enzyme induction, and does not require a sustained elevation of cyclic 3':5'-AMP levels."}
{"id": "PMID:1757", "title": "Properties of a toxin from the sea anemone Stoichacis helianthus, including specific binding to sphingomyelin.", "content": "Stoichactis helianthus toxin, a protein derived presumably from the nematocysts, was purified to homogeneity. It has a molecular weight of about 16,000, an isoelectric pH of 9.8, and it contains approximately 3.7% carbohydrate. It is powerfully hemolytic for erythrocytes derived from a variety of animal species, those of the cat being the most sensitive and those of the guinea pig the most resistant. The toxin is lytic also for rabbit blood platelets, and it destroys cultured fibroblasts but is inactive for several kinds of bacterial protoplasts and spheroplasts. The hemolytic activity is specifically inhibited by sphingomyelin, and it is proposed that this phospholipid is the constituent of the membrane which functions as receptor for the toxin. Supporting evidence includes the findings that enzymes known to destroy sphingomyelin (a) prevent erythrocyte membranes from inhibiting hemolysis, and (b) render erythrocytes resistant to lysis by the toxin. The mechanism underlying hemolysis may involve translocation of membrane sphingomyelin by virtue of a specific affinity of the coelenterate protein for this phospholipid.", "contents": "Properties of a toxin from the sea anemone Stoichacis helianthus, including specific binding to sphingomyelin. Stoichactis helianthus toxin, a protein derived presumably from the nematocysts, was purified to homogeneity. It has a molecular weight of about 16,000, an isoelectric pH of 9.8, and it contains approximately 3.7% carbohydrate. It is powerfully hemolytic for erythrocytes derived from a variety of animal species, those of the cat being the most sensitive and those of the guinea pig the most resistant. The toxin is lytic also for rabbit blood platelets, and it destroys cultured fibroblasts but is inactive for several kinds of bacterial protoplasts and spheroplasts. The hemolytic activity is specifically inhibited by sphingomyelin, and it is proposed that this phospholipid is the constituent of the membrane which functions as receptor for the toxin. Supporting evidence includes the findings that enzymes known to destroy sphingomyelin (a) prevent erythrocyte membranes from inhibiting hemolysis, and (b) render erythrocytes resistant to lysis by the toxin. The mechanism underlying hemolysis may involve translocation of membrane sphingomyelin by virtue of a specific affinity of the coelenterate protein for this phospholipid."}
{"id": "PMID:1758", "title": "Mechanistic studies of glutamine synthetase from Escherichia coli: kinetic evidence for two reaction intermediates in biosynthetic reaction.", "content": "Fast reaction techniques were used to study the kinetics of protein fluorescence intensity changes that are associated with the reactions of unadenylylated Escherichia coli glutamine synthetase [L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2] with its substrates. It was established that the synthesis of glutamine occurs by a stepwise mechanism. During the catalytic process two fluorometrically distinct intermediates were observed. Both forward and reverse rate constants which lead to the formation and consumption of these intermediates were evaluated. The catalytic rate constant, kc, which was calculated from these rate constants agrees well with the values of kc which were determined by direct measurement of the overall biosynthetic activities by means of stopped-flow technique or the steady-state assay method.", "contents": "Mechanistic studies of glutamine synthetase from Escherichia coli: kinetic evidence for two reaction intermediates in biosynthetic reaction. Fast reaction techniques were used to study the kinetics of protein fluorescence intensity changes that are associated with the reactions of unadenylylated Escherichia coli glutamine synthetase [L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2] with its substrates. It was established that the synthesis of glutamine occurs by a stepwise mechanism. During the catalytic process two fluorometrically distinct intermediates were observed. Both forward and reverse rate constants which lead to the formation and consumption of these intermediates were evaluated. The catalytic rate constant, kc, which was calculated from these rate constants agrees well with the values of kc which were determined by direct measurement of the overall biosynthetic activities by means of stopped-flow technique or the steady-state assay method."}
{"id": "PMID:1759", "title": "Molecular mechanism of inhibition of firefly luminescence by local anesthetics.", "content": "The kinetics of the action of local anesthetics upon firefly luciferin and luciferase systems is presented. Clinical concentrations of local anesthetics inhibited this ATP-induced luminescence in a dose-dependent manner. From the effects of temperature and pH upon the inhibitory action of the local anesthetics, it is concluded that hydrophobic ligand-enzyme interaction is the predominant cause of the inhibition, but hydrophilic interaction also contributes to the inhibition to a lesser degree. A molecular theory of anesthesia is outlined which postulates that release of electrostricted water molecules from the hydrophilic parts of the enzyme due to the protein conformational changes induced by anesthetics is the cause of the decreased luminescence. A similar mechanism is expected to occur at the cell membrane, which probably dehydrates the sodium channel and suppresses the conductance of this ion across the membrane. These events lead to a volume expansion of the total system, and the system becomes reactive to a pressure which reverses the anesthesia by shifting the equilibrium to the nonanesthetized original volume. The pressure antagonism of anesthesia can be explained by this overall volume expansion and not by a mere swelling of the cell membrane.", "contents": "Molecular mechanism of inhibition of firefly luminescence by local anesthetics. The kinetics of the action of local anesthetics upon firefly luciferin and luciferase systems is presented. Clinical concentrations of local anesthetics inhibited this ATP-induced luminescence in a dose-dependent manner. From the effects of temperature and pH upon the inhibitory action of the local anesthetics, it is concluded that hydrophobic ligand-enzyme interaction is the predominant cause of the inhibition, but hydrophilic interaction also contributes to the inhibition to a lesser degree. A molecular theory of anesthesia is outlined which postulates that release of electrostricted water molecules from the hydrophilic parts of the enzyme due to the protein conformational changes induced by anesthetics is the cause of the decreased luminescence. A similar mechanism is expected to occur at the cell membrane, which probably dehydrates the sodium channel and suppresses the conductance of this ion across the membrane. These events lead to a volume expansion of the total system, and the system becomes reactive to a pressure which reverses the anesthesia by shifting the equilibrium to the nonanesthetized original volume. The pressure antagonism of anesthesia can be explained by this overall volume expansion and not by a mere swelling of the cell membrane."}
{"id": "PMID:1760", "title": "Cyclic nucleotide metabolism in compensatory renal hypertrophy and neonatal kidney growth.", "content": "Cyclic nucleotide metabolism was investigated in growing kidneys of rats during compensatory hypertrophy and during neonatal development. After unilateral nephrectomy a mild and short-lasting decrease in cyclic 3':5\" adenosine monophosphate (cAMP) was observed in the hypertrophying kidney. In contrast, cyclic 3':5' guanosine monophosphate (cGMP) showed a sharp decline to 20% of control at 15 min and a rapid rise to 200-300% above base-line at 1-72 hr. The alterations in renal tissue levels of cGMP were associated with parallel changes in the soluble, 100,000 X g supernatant guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing): EC 4.6.1.2]. No change was observed in total cGMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase; EC 3.1.4.17). In the rapidly growing kidney of newborn rats cAMP levels were 983 +/- 65 and 833 +/- 42 pmol/g of kidney at 4 and 7 days after birth, and increased to adult levels (1518 +/- 57 pmol/g) at 21 days whereas cGMP levels were 59.8 +/- 6.8 and 92.5 +/- 13.9 pmol/g at 4 and 7 days and decreased to adult levels (36 +/- 1.5) at 21 days. The results indicate that compensatory renal hypertrophy and neonatal kidney growth are associated with changes in cAMP and cGMP metabolism.", "contents": "Cyclic nucleotide metabolism in compensatory renal hypertrophy and neonatal kidney growth. Cyclic nucleotide metabolism was investigated in growing kidneys of rats during compensatory hypertrophy and during neonatal development. After unilateral nephrectomy a mild and short-lasting decrease in cyclic 3':5\" adenosine monophosphate (cAMP) was observed in the hypertrophying kidney. In contrast, cyclic 3':5' guanosine monophosphate (cGMP) showed a sharp decline to 20% of control at 15 min and a rapid rise to 200-300% above base-line at 1-72 hr. The alterations in renal tissue levels of cGMP were associated with parallel changes in the soluble, 100,000 X g supernatant guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing): EC 4.6.1.2]. No change was observed in total cGMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase; EC 3.1.4.17). In the rapidly growing kidney of newborn rats cAMP levels were 983 +/- 65 and 833 +/- 42 pmol/g of kidney at 4 and 7 days after birth, and increased to adult levels (1518 +/- 57 pmol/g) at 21 days whereas cGMP levels were 59.8 +/- 6.8 and 92.5 +/- 13.9 pmol/g at 4 and 7 days and decreased to adult levels (36 +/- 1.5) at 21 days. The results indicate that compensatory renal hypertrophy and neonatal kidney growth are associated with changes in cAMP and cGMP metabolism."}
{"id": "PMID:1790", "title": "Effects of denaturants on the sweet-tasting protein monellin.", "content": "Effects of the denaturants urea and guanidine-HCl on the sweet-tasting protein monellin have been studied. The pH at which monellin is initially treated with denaturant is an important factor in retention of sweetness, but the pH maintained during subsequent removal of denaturant by dialysis has no effect on activity. Recovery of sweetness of denaturant-treated monellin is favored when denaturation occurs at acid pH. Monellin treated with either 6 M guanidine-HCl or 8 M urea at acid pH retains all of its sweetness following removal of denaturant, but urea treatment at neutral pH leads to some irreversible loss of sweetness. Monellin precipitates from solution under some conditions during removal of denaturant by dialysis, and the precipitated protein is no longer sweet. Precipitation is least under acid conditions. Aggregated protein was demonstrated by gel filtration chromatography. The single sulfhydryl group of monellin was not demonstrable in the precipitated protein, having apparently become oxidized during denaturation and formation of the aggregated protein. The data support the hypothesis that the tertiary structure is important in the ability of monellin to elicit a sweet sensation.", "contents": "Effects of denaturants on the sweet-tasting protein monellin. Effects of the denaturants urea and guanidine-HCl on the sweet-tasting protein monellin have been studied. The pH at which monellin is initially treated with denaturant is an important factor in retention of sweetness, but the pH maintained during subsequent removal of denaturant by dialysis has no effect on activity. Recovery of sweetness of denaturant-treated monellin is favored when denaturation occurs at acid pH. Monellin treated with either 6 M guanidine-HCl or 8 M urea at acid pH retains all of its sweetness following removal of denaturant, but urea treatment at neutral pH leads to some irreversible loss of sweetness. Monellin precipitates from solution under some conditions during removal of denaturant by dialysis, and the precipitated protein is no longer sweet. Precipitation is least under acid conditions. Aggregated protein was demonstrated by gel filtration chromatography. The single sulfhydryl group of monellin was not demonstrable in the precipitated protein, having apparently become oxidized during denaturation and formation of the aggregated protein. The data support the hypothesis that the tertiary structure is important in the ability of monellin to elicit a sweet sensation."}
{"id": "PMID:1791", "title": "Thyroxine deiodination associated with NADPH-dependent lipid peroxidation in a submicrosomal system.", "content": "A lipoprotein present in trypsin-treated microsomes can be oxidized with formation of malondialdehyde in a system which contains NADPH, ferric ion-ADP complex, NADPH-cytochrome c reductase and a factor. This factor, a mixture of peptides, can be isolated from hepatic microsomes by trypsin digestion and successive gel filtration through Sephadex G-100 and G-25 columns. Lipid peroxidation in this system catalyzes the deiodination of thyroxine, as does NADPH-dependent lipid peroxidation in fresh hepatic microsomes. Thyroxine inhibits lipid peroxidation as it is deiodinated in this system.", "contents": "Thyroxine deiodination associated with NADPH-dependent lipid peroxidation in a submicrosomal system. A lipoprotein present in trypsin-treated microsomes can be oxidized with formation of malondialdehyde in a system which contains NADPH, ferric ion-ADP complex, NADPH-cytochrome c reductase and a factor. This factor, a mixture of peptides, can be isolated from hepatic microsomes by trypsin digestion and successive gel filtration through Sephadex G-100 and G-25 columns. Lipid peroxidation in this system catalyzes the deiodination of thyroxine, as does NADPH-dependent lipid peroxidation in fresh hepatic microsomes. Thyroxine inhibits lipid peroxidation as it is deiodinated in this system."}
{"id": "PMID:1792", "title": "Effect of environmental pH on adenovirus-associated virus.", "content": "The influence of environmental pH on AAV was studied in infectious virus titrations, induction of CF antigens production of infectious virus, induction of immunofluorescent stainable antigen, and aggregation of the viral particles. The pH of the medium was found to influence the titer of virus stocks in that less virus was registered at acid pH's, giving differences of up to 105 TCID50 in HEK and HEp-2 cells. Less infectious virus was produced in KB cells, and decreased amounts of CF antigen appeared at acid pH's. However, increased levels of detectable intracellular FA antigen appeared at acid pH's. Electron microscopic examination of AAV particles negatively stained at various pH's showed increasingly large aggregates of particles as the pH was lowered. Under the acid conditions studied, the adenovirus helper and cell activities were only slightly suppressed, with the greatest effect due to aggregation of the virus particles.", "contents": "Effect of environmental pH on adenovirus-associated virus. The influence of environmental pH on AAV was studied in infectious virus titrations, induction of CF antigens production of infectious virus, induction of immunofluorescent stainable antigen, and aggregation of the viral particles. The pH of the medium was found to influence the titer of virus stocks in that less virus was registered at acid pH's, giving differences of up to 105 TCID50 in HEK and HEp-2 cells. Less infectious virus was produced in KB cells, and decreased amounts of CF antigen appeared at acid pH's. However, increased levels of detectable intracellular FA antigen appeared at acid pH's. Electron microscopic examination of AAV particles negatively stained at various pH's showed increasingly large aggregates of particles as the pH was lowered. Under the acid conditions studied, the adenovirus helper and cell activities were only slightly suppressed, with the greatest effect due to aggregation of the virus particles."}
{"id": "PMID:1793", "title": "The effect of dexamethasone on urinary acidification.", "content": "Although it is well recognized that mineralocorticoids enhance renal acid excretion, the effect of glucocorticoids on renal acidification is unclear. Oral administration of dexamethasone to six healthy volunteers for 1 week at a daily dose of 4.5 mg was associated with mild respiratory alkalosis and a small but statistically significant increase in baseline urine pH. However, neither the ability to lower urine pH nor to excrete titratable acid and ammonium after NH4Cl acid-loading was altered. Administration of a single intravenous dose of dexamethasone sodium phosphate (7.5 mg) was associated with a significant rise in urine pH and potassium excretion and decreased titratable acid, ammonium , and phosphorus excretion in the absence of changes in blood acid-base status, creatinine clearance, or urine flow.", "contents": "The effect of dexamethasone on urinary acidification. Although it is well recognized that mineralocorticoids enhance renal acid excretion, the effect of glucocorticoids on renal acidification is unclear. Oral administration of dexamethasone to six healthy volunteers for 1 week at a daily dose of 4.5 mg was associated with mild respiratory alkalosis and a small but statistically significant increase in baseline urine pH. However, neither the ability to lower urine pH nor to excrete titratable acid and ammonium after NH4Cl acid-loading was altered. Administration of a single intravenous dose of dexamethasone sodium phosphate (7.5 mg) was associated with a significant rise in urine pH and potassium excretion and decreased titratable acid, ammonium , and phosphorus excretion in the absence of changes in blood acid-base status, creatinine clearance, or urine flow."}
{"id": "PMID:1795", "title": "A rapid method for measuring guanylate cyclase activity in mammary tissue.", "content": "A simple and rapid method for measuring guanylate cyclase activity in broken cell preparations of biological tissues is described. This method employs the rate of conversion of [32P]GTP to [32P]cyclic-GMP. The product of this reaction is isolated by ion-exchange chromatography and by a ZnSO4-Ba(OH)2 precipitation at pH 5.7. Using this method, about 30-50 samples can be assayed for guanylate cyclase activity during a 5-6 hr period. The characteristics of this enzyme in the mammary gland were found to be similar to those described for other tissues using different methods for measuring guanylate cyclase activity.", "contents": "A rapid method for measuring guanylate cyclase activity in mammary tissue. A simple and rapid method for measuring guanylate cyclase activity in broken cell preparations of biological tissues is described. This method employs the rate of conversion of [32P]GTP to [32P]cyclic-GMP. The product of this reaction is isolated by ion-exchange chromatography and by a ZnSO4-Ba(OH)2 precipitation at pH 5.7. Using this method, about 30-50 samples can be assayed for guanylate cyclase activity during a 5-6 hr period. The characteristics of this enzyme in the mammary gland were found to be similar to those described for other tissues using different methods for measuring guanylate cyclase activity."}
{"id": "PMID:1796", "title": "Guanylate cyclase and cyclic-GMP phosphodiesterase activities in mammary glands of mice during pregnancy and lactation.", "content": "Guanylate cyclase and cyclic-GMP phosphodiesterase activities were measured in homogenates of mammary glands from virgin, pregnant, and lactating mice. Guanylate cyclase activities increased 35% in mammary tissues during pregnancy, and a further 40% increase was observed during lactation. Cyclic-GMP phosphodiesterase activity also increased during pregnancy but activities were not different in glands from lactating mice vs glands from pregnant mice. These results are discussed with regard to a possible role of cyclic-GMP in regulating lactational processes.", "contents": "Guanylate cyclase and cyclic-GMP phosphodiesterase activities in mammary glands of mice during pregnancy and lactation. Guanylate cyclase and cyclic-GMP phosphodiesterase activities were measured in homogenates of mammary glands from virgin, pregnant, and lactating mice. Guanylate cyclase activities increased 35% in mammary tissues during pregnancy, and a further 40% increase was observed during lactation. Cyclic-GMP phosphodiesterase activity also increased during pregnancy but activities were not different in glands from lactating mice vs glands from pregnant mice. These results are discussed with regard to a possible role of cyclic-GMP in regulating lactational processes."}
{"id": "PMID:1797", "title": "Cyclic-AMP and pancreatic bicarbonate secretion in response to secretin in dogs.", "content": "In anesthetized dogs given secretin intravenously in doses doubling every 60 min and ranging from 0.5 to 8 units per kg body weight per hr, cyclic-AMP levels in pancreatic tissue rose continuously, whereas DNA concentrations were slightly decreased. Bicarbonate concentrations and bicarbonate outputs, cyclic-AMP tissue concentrations and bicarbonate outputs, as well as cyclic-AMP tissue concentrations and juice outputs, were significantly correlated. In conscious pancreatic fistula dogs, there was also a significant correlation between cyclic-AMP and bicarbonate concentrations and outputs in the pancreatic juice after stimulation by exogenous secretin. Accordingly, enhanced release of endogenous secretin achieved by intraduodenal acidification led to a dose-dependent increase in bicarbonate and cyclic-AMP outputs in both conscious and anesthetized dogs. Phosphodiesterase inhibitors (aminophylline, caffeine, and papaverine) given alone to the conscious dogs did not initiate pancreatic bicarbonate secretion, but they potentiated bicarbonate responses to exogenous secretin. These data suggest that cyclic-AMP plays a part in secretin-stimulated pancreatic secretion.", "contents": "Cyclic-AMP and pancreatic bicarbonate secretion in response to secretin in dogs. In anesthetized dogs given secretin intravenously in doses doubling every 60 min and ranging from 0.5 to 8 units per kg body weight per hr, cyclic-AMP levels in pancreatic tissue rose continuously, whereas DNA concentrations were slightly decreased. Bicarbonate concentrations and bicarbonate outputs, cyclic-AMP tissue concentrations and bicarbonate outputs, as well as cyclic-AMP tissue concentrations and juice outputs, were significantly correlated. In conscious pancreatic fistula dogs, there was also a significant correlation between cyclic-AMP and bicarbonate concentrations and outputs in the pancreatic juice after stimulation by exogenous secretin. Accordingly, enhanced release of endogenous secretin achieved by intraduodenal acidification led to a dose-dependent increase in bicarbonate and cyclic-AMP outputs in both conscious and anesthetized dogs. Phosphodiesterase inhibitors (aminophylline, caffeine, and papaverine) given alone to the conscious dogs did not initiate pancreatic bicarbonate secretion, but they potentiated bicarbonate responses to exogenous secretin. These data suggest that cyclic-AMP plays a part in secretin-stimulated pancreatic secretion."}
{"id": "PMID:1798", "title": "Effects in the rat of intradermal injection of purified proteinases from streptococcus and Serratia marcescens.", "content": "Purified streptococcal proteinase and Serratia proteinase are potent permeability factors in rat skin and initiate histopathological evidence of an acute inflammatory response. These effects appear to be largely independent of terminal components of complement, histamine, and polymorphonuclear leukocytes.", "contents": "Effects in the rat of intradermal injection of purified proteinases from streptococcus and Serratia marcescens. Purified streptococcal proteinase and Serratia proteinase are potent permeability factors in rat skin and initiate histopathological evidence of an acute inflammatory response. These effects appear to be largely independent of terminal components of complement, histamine, and polymorphonuclear leukocytes."}
{"id": "PMID:1802", "title": "Comparison of beta-adrenoceptor blocking properties of sotalol, oxprenolol, propranolol and pindolol on rabbit intestinal smooth muscle.", "content": "Adrenergic agonists produced a characteristic and definite decrease in the amplitude of spontaneous contractions and tone of the isolated rabbit jejunum. Effect of phenylephrine was abolished either by phenoxybenzamine or phentolamine. Relaxation induced by epinephrine and by norepinephrine was inhibited after combined treatment with phentolamine and propranolol. Phentolamine alone diminished the response to epinephrine and to norepinephrine, but the diminution for epinephrine was greater, indicating that epinephrine has a greater affinity for alpha- than for beta-receptors in the rabbit jejunum. Stimulation of the beta-receptors by isoproterenol was inhibited by propranolol, oxprenolol, sotalol and pindolol, but the block was incomplete. The activity of these four beta-blockers in preventing the inhibitory response to isoproterenol was as follows: inidolol greater than or equal to oxprenolol greater than propranolol greater than sotalol. This demonstrates the fact that not all beta-adrenergic blocking agents possess an identical pharmacologic spectrum of activity. Also it can be suggested that the beta-receptors of jejunum differ in specificity from those of other organs.", "contents": "Comparison of beta-adrenoceptor blocking properties of sotalol, oxprenolol, propranolol and pindolol on rabbit intestinal smooth muscle. Adrenergic agonists produced a characteristic and definite decrease in the amplitude of spontaneous contractions and tone of the isolated rabbit jejunum. Effect of phenylephrine was abolished either by phenoxybenzamine or phentolamine. Relaxation induced by epinephrine and by norepinephrine was inhibited after combined treatment with phentolamine and propranolol. Phentolamine alone diminished the response to epinephrine and to norepinephrine, but the diminution for epinephrine was greater, indicating that epinephrine has a greater affinity for alpha- than for beta-receptors in the rabbit jejunum. Stimulation of the beta-receptors by isoproterenol was inhibited by propranolol, oxprenolol, sotalol and pindolol, but the block was incomplete. The activity of these four beta-blockers in preventing the inhibitory response to isoproterenol was as follows: inidolol greater than or equal to oxprenolol greater than propranolol greater than sotalol. This demonstrates the fact that not all beta-adrenergic blocking agents possess an identical pharmacologic spectrum of activity. Also it can be suggested that the beta-receptors of jejunum differ in specificity from those of other organs."}
{"id": "PMID:1799", "title": "Effect of recurrent stress on postnatal increase of tyrosine hydroxylase.", "content": "Tyrosine hydroxylase is present at birth and reaches adult levels in the hypothalamus usually during the second month. Recurrent stimulation of intrahypothalamic noradrenergic structures shortened this period of maturation in a statistically significant manner.", "contents": "Effect of recurrent stress on postnatal increase of tyrosine hydroxylase. Tyrosine hydroxylase is present at birth and reaches adult levels in the hypothalamus usually during the second month. Recurrent stimulation of intrahypothalamic noradrenergic structures shortened this period of maturation in a statistically significant manner."}
{"id": "PMID:1803", "title": "The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties.", "content": "Mice were given a drug per os and 2 h later were challenged with an intravenous LD95 of nicotine. Amitriptyline, imipramine, doxepin, meprobamate, chlordiazepoxide, diazepam, trifluoroperazine, haloperidol, thioridazine, chlorpromazine, phenobarbital, propranolol and diphenylhydantoin were all active in protecting mice from extensor convulsions and lethality. Iproniazid, tranylcypromine, atropine, benztropine and trimethadione were inactive. There appears to be a relationship between blockage of nicotine-induced extensor convulsions and lethality in mice and sedative-antianxiety effects in man. This relationship is especially good for drugs designated antidepressant, antianxiety and antipsychotic.", "contents": "The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties. Mice were given a drug per os and 2 h later were challenged with an intravenous LD95 of nicotine. Amitriptyline, imipramine, doxepin, meprobamate, chlordiazepoxide, diazepam, trifluoroperazine, haloperidol, thioridazine, chlorpromazine, phenobarbital, propranolol and diphenylhydantoin were all active in protecting mice from extensor convulsions and lethality. Iproniazid, tranylcypromine, atropine, benztropine and trimethadione were inactive. There appears to be a relationship between blockage of nicotine-induced extensor convulsions and lethality in mice and sedative-antianxiety effects in man. This relationship is especially good for drugs designated antidepressant, antianxiety and antipsychotic."}
{"id": "PMID:1800", "title": "Effect of propranolol on antinociceptive and withdrawal characteristics of morphine.", "content": "Propranolol at a dose (10 mg/kg) which did not alter tail-flick latency by itself, did not alter the ED50 of morphine when given 10 min prior to the narcotic. Propranolol at doses of 10 and 25 mg/kg given 10 min prior to naloxone challenge did not significantly alter the frequency of naloxone induced jumping 72 hr after morphine pellet implantation. The ED50 of naloxone in morphine pelleted mice was not altered by treatment with propranolol at 0, 24, and 48 hr after pellet implantation. Naloxone caused hyperactivity in mice when administered 72 hr after morphine pellet implantation. An injection of 25 mg/kg propranolol 10 min prior to naloxone did not block this hyperactivity. In addition, administration of 10 mg/kg of propranolol every 8 hr to rats during withdrawal from morphine failed to alleviate the withdrawal syndrome as evidenced by changes in either body weight or water intake. These data suggest that the beta-adrenergic blocking agent, propranolol, does not alter the antinociceptive activity or lessen the withdrawal syndrome of morphine in rodents.", "contents": "Effect of propranolol on antinociceptive and withdrawal characteristics of morphine. Propranolol at a dose (10 mg/kg) which did not alter tail-flick latency by itself, did not alter the ED50 of morphine when given 10 min prior to the narcotic. Propranolol at doses of 10 and 25 mg/kg given 10 min prior to naloxone challenge did not significantly alter the frequency of naloxone induced jumping 72 hr after morphine pellet implantation. The ED50 of naloxone in morphine pelleted mice was not altered by treatment with propranolol at 0, 24, and 48 hr after pellet implantation. Naloxone caused hyperactivity in mice when administered 72 hr after morphine pellet implantation. An injection of 25 mg/kg propranolol 10 min prior to naloxone did not block this hyperactivity. In addition, administration of 10 mg/kg of propranolol every 8 hr to rats during withdrawal from morphine failed to alleviate the withdrawal syndrome as evidenced by changes in either body weight or water intake. These data suggest that the beta-adrenergic blocking agent, propranolol, does not alter the antinociceptive activity or lessen the withdrawal syndrome of morphine in rodents."}
{"id": "PMID:1801", "title": "Increased acquisition of a complex appetitive task after MSH and MIF.", "content": "After daily injections of melanocyte stimulating hormone (MSH), MSH-release inhibiting factor (MIF), or diluent albino rats ran a 12 choice Warden maze for a palatable food reward. Rats receiving the hormones had shorter latencies and made fewer errors than controls during learning but, unlike results with simple tasks, there were no differences during extinction. The results demonstrated that both MSH and MIF-I could facilitate the acquisition of an appetitive task which seemed of sufficient complexity to emphasize differences in performance.", "contents": "Increased acquisition of a complex appetitive task after MSH and MIF. After daily injections of melanocyte stimulating hormone (MSH), MSH-release inhibiting factor (MIF), or diluent albino rats ran a 12 choice Warden maze for a palatable food reward. Rats receiving the hormones had shorter latencies and made fewer errors than controls during learning but, unlike results with simple tasks, there were no differences during extinction. The results demonstrated that both MSH and MIF-I could facilitate the acquisition of an appetitive task which seemed of sufficient complexity to emphasize differences in performance."}
{"id": "PMID:1804", "title": "The jumping mechanism of Xenopsylla cheopis. I. Exoskeletal structures and musculature.", "content": "The jumping apparatus of the flea, which includes highly modified direct and indirect flight muscles, is described: attention is drawn to the various specializations of the exoskeleton which stiffen the thorax and also provide the 'click' mechanism triggering take-off. A finger-like invagination of tall cells within the cavity of the developing pleural arch of the pharate adult secretes the resilin pad. This is illustrated with coloured photographs. It is suggested that winglessness of a Mecopteran-like ancestor pre-adapted fleas to a parasitic life-style, and that a jumping mode of progression was a primitive feature of the whole Order. Scattered throughout the Siphonaptera today are species which have secondarily lost the pleural arch and with it the power to execute large jumps. These are usually found among fleas parasitizing mammals inhabiting caves, subterranean burrows and runs, high aerial nests and snow or ice-bound habitats. Large pleural arches are associated with fleas infesting large mobile hosts.", "contents": "The jumping mechanism of Xenopsylla cheopis. I. Exoskeletal structures and musculature. The jumping apparatus of the flea, which includes highly modified direct and indirect flight muscles, is described: attention is drawn to the various specializations of the exoskeleton which stiffen the thorax and also provide the 'click' mechanism triggering take-off. A finger-like invagination of tall cells within the cavity of the developing pleural arch of the pharate adult secretes the resilin pad. This is illustrated with coloured photographs. It is suggested that winglessness of a Mecopteran-like ancestor pre-adapted fleas to a parasitic life-style, and that a jumping mode of progression was a primitive feature of the whole Order. Scattered throughout the Siphonaptera today are species which have secondarily lost the pleural arch and with it the power to execute large jumps. These are usually found among fleas parasitizing mammals inhabiting caves, subterranean burrows and runs, high aerial nests and snow or ice-bound habitats. Large pleural arches are associated with fleas infesting large mobile hosts."}
{"id": "PMID:1805", "title": "The jumping mechanism of Xenopsylla cheopis. II. The fine structure of the jumping muscle.", "content": "The ultrastructure of the trochanteral depressor muscle of the oriental rat flea is described. It is shown to be similar to that of the tubular leg muscles of other insects except in the volume and arrangement of the sarcoplasmic reticulum. The sarcoplasmic reticulum occupies approximately 18% of the volume of the muscle fibres. It is in three configurations:a regular array of parallel tubules opposite the A-band, a collar of sacculi involved in the formation of the dyads at the edge of the A-band and a loosely woven arrangement of tubules around the I-band. This tripartite arrangement of the sarcoplasmic reticulum and its large surface area is discussed in relation to the action of the muscle as the main propulsive muscle in the jump of the flea.", "contents": "The jumping mechanism of Xenopsylla cheopis. II. The fine structure of the jumping muscle. The ultrastructure of the trochanteral depressor muscle of the oriental rat flea is described. It is shown to be similar to that of the tubular leg muscles of other insects except in the volume and arrangement of the sarcoplasmic reticulum. The sarcoplasmic reticulum occupies approximately 18% of the volume of the muscle fibres. It is in three configurations:a regular array of parallel tubules opposite the A-band, a collar of sacculi involved in the formation of the dyads at the edge of the A-band and a loosely woven arrangement of tubules around the I-band. This tripartite arrangement of the sarcoplasmic reticulum and its large surface area is discussed in relation to the action of the muscle as the main propulsive muscle in the jump of the flea."}
{"id": "PMID:1806", "title": "The jumping mechanism of Xenopsylla cheopis. III. Execution of the jump and activity.", "content": "The flea's hind legs are the chief source of jumping power, but in species which execute large jumps, take-off is accelerated by elastic energy released from a resilin pad (homologous with the wing hinge ligaments of flying insects) situated in the pleural arch. A central click mechanism, operated by a rapid twitch of the trochanteral depressor (the starter muscle), synchronizes the separate sources of energy which power the jump. Cin\u00e9 photos confirm the morphological evidence that the flea takes off from the trochanters, not the tarsi. The loss of wings, associated with lateral compression of the body and the shortening of the pleural ridge (which thus lowers the position of the pleural arch) together with modifications of the direct and indirect flight muscles, are some of the main morphological features associated with the change from a flying to a saltatorial mode of progression. The flea's take-off basically resembles that of other Panorpoid insects (Diptera, Mecoptera, etc.). The release of elastic energy from the pleural arch is a system by which the force used to move the wings of flying insects is rapidly fed back into the legs and adds power to the jump.", "contents": "The jumping mechanism of Xenopsylla cheopis. III. Execution of the jump and activity. The flea's hind legs are the chief source of jumping power, but in species which execute large jumps, take-off is accelerated by elastic energy released from a resilin pad (homologous with the wing hinge ligaments of flying insects) situated in the pleural arch. A central click mechanism, operated by a rapid twitch of the trochanteral depressor (the starter muscle), synchronizes the separate sources of energy which power the jump. Cin\u00e9 photos confirm the morphological evidence that the flea takes off from the trochanters, not the tarsi. The loss of wings, associated with lateral compression of the body and the shortening of the pleural ridge (which thus lowers the position of the pleural arch) together with modifications of the direct and indirect flight muscles, are some of the main morphological features associated with the change from a flying to a saltatorial mode of progression. The flea's take-off basically resembles that of other Panorpoid insects (Diptera, Mecoptera, etc.). The release of elastic energy from the pleural arch is a system by which the force used to move the wings of flying insects is rapidly fed back into the legs and adds power to the jump."}
{"id": "PMID:1808", "title": "Self-assembly of biological macromolecules.", "content": "The genetic apparatus of the cell is responsible for the accurate biosynthesis of the primary structure of macromolecules which then spontaneously fold up and, in certain circumstances, aggregate to yield the complex tertiary and quaternary structures of the biologically active molecules. Structures capable of self-assembly in this range from simple monomers through oligomers to complex multimeric structures that may contain more than one type of polypeptide chain and components other than protein. It is becoming clear that even with the simpler monomeric enzymes there is becoming clear that even with the simpler monomeric enzymes there is a kinetically determined pathway for the folding process and that a folded protein must now be regarded as the minimum free energy form of the kinetically accessible conformations. It is argued that the denatured subunits of oligomeric enzymes are likely to fold to something like their final structure before aggregating to give the native quaternary structure and the available evidence would suggest that this is so. The importance of nucleation events and stable intermediates in the self-assembly of more complex structures is clear. Many self-assembling structures contain only identical subunits and symmetry arguments are very successful in accounting for the structures formed. Because proteins are themselves complex molecules and not inelastic geometric objects, the rules of strict symmetry can be bent and quasi-equivalent bonding between subunits permitted. This possibility is frequently employed in biological structures. Conversely, symmetry arguments can offer a reliable means of choosing between alternative models for a given structure. It can be seen that proteins gain stability by growing larger and it is argued in evolutionary terms that aggregation of subunits is the preferred way to increase the size of proteins. The possession of quaternary structure by enzymes allows conferral of other biologically important properties, such as cooperativity between active sites, changes of specificity, substrate channelling and sequential reactions within a multi-enzyme complex. Comparison is made of the invariant subunit compositions of the simpler oligomeric enzymes with the variation evidently open to, say, the 2-oxoacid dehydrogenase complexes of E. coli. With viruses, on the other hand, the function of the quaternary structure is to package nucleic acid and, as an example, the assembly and breakdown of tobacco mosaic virus is discussed. Attention is drawn to the possible ways in which the principles of self-assembly can be extended to make structures more complicated than those that can be formed by simple aggregation of the comonent parts.", "contents": "Self-assembly of biological macromolecules. The genetic apparatus of the cell is responsible for the accurate biosynthesis of the primary structure of macromolecules which then spontaneously fold up and, in certain circumstances, aggregate to yield the complex tertiary and quaternary structures of the biologically active molecules. Structures capable of self-assembly in this range from simple monomers through oligomers to complex multimeric structures that may contain more than one type of polypeptide chain and components other than protein. It is becoming clear that even with the simpler monomeric enzymes there is becoming clear that even with the simpler monomeric enzymes there is a kinetically determined pathway for the folding process and that a folded protein must now be regarded as the minimum free energy form of the kinetically accessible conformations. It is argued that the denatured subunits of oligomeric enzymes are likely to fold to something like their final structure before aggregating to give the native quaternary structure and the available evidence would suggest that this is so. The importance of nucleation events and stable intermediates in the self-assembly of more complex structures is clear. Many self-assembling structures contain only identical subunits and symmetry arguments are very successful in accounting for the structures formed. Because proteins are themselves complex molecules and not inelastic geometric objects, the rules of strict symmetry can be bent and quasi-equivalent bonding between subunits permitted. This possibility is frequently employed in biological structures. Conversely, symmetry arguments can offer a reliable means of choosing between alternative models for a given structure. It can be seen that proteins gain stability by growing larger and it is argued in evolutionary terms that aggregation of subunits is the preferred way to increase the size of proteins. The possession of quaternary structure by enzymes allows conferral of other biologically important properties, such as cooperativity between active sites, changes of specificity, substrate channelling and sequential reactions within a multi-enzyme complex. Comparison is made of the invariant subunit compositions of the simpler oligomeric enzymes with the variation evidently open to, say, the 2-oxoacid dehydrogenase complexes of E. coli. With viruses, on the other hand, the function of the quaternary structure is to package nucleic acid and, as an example, the assembly and breakdown of tobacco mosaic virus is discussed. Attention is drawn to the possible ways in which the principles of self-assembly can be extended to make structures more complicated than those that can be formed by simple aggregation of the comonent parts."}
{"id": "PMID:1807", "title": "Dynamic aspects of enzyme specificity.", "content": "There are two aspects of enzyme specificity: recognition of the substrate by the formation of an enzyme-substrate compound and recognition of the transition state by catalysis of the reaction. Kinetic studies with inactive substrate analogues as potential competitive inhibitors, and structural studies of their compounds with enzymes, give information about the first of these specificity elements. Comparative kinetic studies with alternative substrates give information about both. There is a great deal of information from kinetic studies of dehydrogenases about the coenzyme specificities, substrate specificities and stereospecificities and mechanisms of these enzymes, particularly alcohol dehydrogenases. Recent X-ray diffraction studies of dehydrogenases have given insight into the molecular basis of some of their specificity elements. An attempt is made to correlate the available kinetic and structural data for alcohol and lactate dehydrogenases.", "contents": "Dynamic aspects of enzyme specificity. There are two aspects of enzyme specificity: recognition of the substrate by the formation of an enzyme-substrate compound and recognition of the transition state by catalysis of the reaction. Kinetic studies with inactive substrate analogues as potential competitive inhibitors, and structural studies of their compounds with enzymes, give information about the first of these specificity elements. Comparative kinetic studies with alternative substrates give information about both. There is a great deal of information from kinetic studies of dehydrogenases about the coenzyme specificities, substrate specificities and stereospecificities and mechanisms of these enzymes, particularly alcohol dehydrogenases. Recent X-ray diffraction studies of dehydrogenases have given insight into the molecular basis of some of their specificity elements. An attempt is made to correlate the available kinetic and structural data for alcohol and lactate dehydrogenases."}
{"id": "PMID:1809", "title": "Water structure and hydration.", "content": "Possible structures adopted by bulk water are discussed with special reference to the possible presence of monomeric water and the detection of 'free' -OH groups. The way in which water tends to accommodate small hydrophobic molecules is considered, with particular reference to the clathrate theory and the phenomenon of 'structure making'. Cage-pairing and cage-sharing processes are described. Consideration of the way water solvates cations and anions is followed by a discussion of the way these solvated ions interact with the bulk medium. Large symmetrical alkylammonium ions probably encourage clathrate cage formation, at least at low temperatures. Particular reference is made to the use of infrared, Raman, ultraviolet, n.m.r. and e.s.r. spectroscopic techniques to the study of water and aqueous solutions.", "contents": "Water structure and hydration. Possible structures adopted by bulk water are discussed with special reference to the possible presence of monomeric water and the detection of 'free' -OH groups. The way in which water tends to accommodate small hydrophobic molecules is considered, with particular reference to the clathrate theory and the phenomenon of 'structure making'. Cage-pairing and cage-sharing processes are described. Consideration of the way water solvates cations and anions is followed by a discussion of the way these solvated ions interact with the bulk medium. Large symmetrical alkylammonium ions probably encourage clathrate cage formation, at least at low temperatures. Particular reference is made to the use of infrared, Raman, ultraviolet, n.m.r. and e.s.r. spectroscopic techniques to the study of water and aqueous solutions."}
{"id": "PMID:1810", "title": "Drug-nucleic acid interaction: X-ray crystallographic determination of an ethidium-dinucleoside monophosphate crystalline complex, ethidium: 5-iodouridylyl(3'-5')adenosine.", "content": "The intercalative trypanosomal drug, ethidium bromide, forms a crystalline complex with the dinucleoside monophosphate, 5-iodiuridylyl(3'-5')adenosine (iodoUpA). These crystals are monoclinic, space group C2, with unit cell dimensions, a = 2.845 nm, b = 1.354 nm, c = 3.413 nm, beta = 98.6 degrees. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares to a residual of 0.29 on 2017 observed reflexions. The asymmetric unit contains two ethidium molecules, two iodoUpA molecules, twenty water molecules and four methanol molecules, a total of 156 atims excluding hydrogens. The two iodoUpA molecules are held together by adenine-uracil Watson-Crick base-pairing. Adjacent base-pairs within this paired iodoUpA structure and between neighbouring iodoUpA molecules in adjoining unit cells  are separated by 0.68 nm. This separation results from intercalative binding by one ethidium molecule and stacking by the other symmetry is utilized in this model drub-nucleic acid interaction, the intercalative ethidium molecule being oriented such that its phenyl and ethyl groups lie in the narrow groove of the miniature nucleic acid double helix. Solution studies have indicated a marked sequence specificity for ethidium-dinucleotide interactions and a probable structural explanation for this has been provided by this study.", "contents": "Drug-nucleic acid interaction: X-ray crystallographic determination of an ethidium-dinucleoside monophosphate crystalline complex, ethidium: 5-iodouridylyl(3'-5')adenosine. The intercalative trypanosomal drug, ethidium bromide, forms a crystalline complex with the dinucleoside monophosphate, 5-iodiuridylyl(3'-5')adenosine (iodoUpA). These crystals are monoclinic, space group C2, with unit cell dimensions, a = 2.845 nm, b = 1.354 nm, c = 3.413 nm, beta = 98.6 degrees. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares to a residual of 0.29 on 2017 observed reflexions. The asymmetric unit contains two ethidium molecules, two iodoUpA molecules, twenty water molecules and four methanol molecules, a total of 156 atims excluding hydrogens. The two iodoUpA molecules are held together by adenine-uracil Watson-Crick base-pairing. Adjacent base-pairs within this paired iodoUpA structure and between neighbouring iodoUpA molecules in adjoining unit cells  are separated by 0.68 nm. This separation results from intercalative binding by one ethidium molecule and stacking by the other symmetry is utilized in this model drub-nucleic acid interaction, the intercalative ethidium molecule being oriented such that its phenyl and ethyl groups lie in the narrow groove of the miniature nucleic acid double helix. Solution studies have indicated a marked sequence specificity for ethidium-dinucleotide interactions and a probable structural explanation for this has been provided by this study."}
{"id": "PMID:1811", "title": "DNA-RNA hybridization.", "content": "Interest in nucleic acid hybridization stems mainly from its great power as a tool in biological research. It is used in several quite distinct ways. Because of the high degree of specificity that they show, hybridization techniques can be used to measure the amount of one specific sequence within a very heterogeneous mixture of sequences. Measurements of 1/10(6)-10(7) have been recorded. In extension of this, various properties of a specific sequence can often be studied. Secondly, because the kinetics of nucleic acid hybridization are quite well understood, it can be used to characterize both a pure sequence and a very complex mixture of sequences, like the genome of a vertebrate. Thirdly, again because of its specificity, it can be used to measure homologies between different populations of nucleic acids. Lastly, in conjunction with other techniques, it can be used as a basis for the fractionation of nucleic acid populations and the purification of specific sequences. Specific examples of these applications are given, with special reference to the organization of the genome in higher eukaryotes.", "contents": "DNA-RNA hybridization. Interest in nucleic acid hybridization stems mainly from its great power as a tool in biological research. It is used in several quite distinct ways. Because of the high degree of specificity that they show, hybridization techniques can be used to measure the amount of one specific sequence within a very heterogeneous mixture of sequences. Measurements of 1/10(6)-10(7) have been recorded. In extension of this, various properties of a specific sequence can often be studied. Secondly, because the kinetics of nucleic acid hybridization are quite well understood, it can be used to characterize both a pure sequence and a very complex mixture of sequences, like the genome of a vertebrate. Thirdly, again because of its specificity, it can be used to measure homologies between different populations of nucleic acids. Lastly, in conjunction with other techniques, it can be used as a basis for the fractionation of nucleic acid populations and the purification of specific sequences. Specific examples of these applications are given, with special reference to the organization of the genome in higher eukaryotes."}
{"id": "PMID:1812", "title": "The dynamic properties of biological membranes.", "content": "Biological membranes must be viewed as highly dynamic, undergoing continuous structural fluctuations and changes in response to external perturbations. The study of liposomes by 31 P n.m.r. and fluorescence can reveal some of the motional characteristics of the different regions in a bilayer. Asymmetric lipid distribution and how this depends on the environment is also observed by n.m.r. The nature of the interaction of amine anaesthetics and of polypeptide antibodies with membranes is discussed in relation to their perturbing effect. The role of lipid mobility in modulating hormone-receptor interaction is discussed with reference to the binding of thyroid stimulating hormone.", "contents": "The dynamic properties of biological membranes. Biological membranes must be viewed as highly dynamic, undergoing continuous structural fluctuations and changes in response to external perturbations. The study of liposomes by 31 P n.m.r. and fluorescence can reveal some of the motional characteristics of the different regions in a bilayer. Asymmetric lipid distribution and how this depends on the environment is also observed by n.m.r. The nature of the interaction of amine anaesthetics and of polypeptide antibodies with membranes is discussed in relation to their perturbing effect. The role of lipid mobility in modulating hormone-receptor interaction is discussed with reference to the binding of thyroid stimulating hormone."}
{"id": "PMID:1813", "title": "Recognition at cell surfaces: phytohaemagglutinin-lymphocyte interaction.", "content": "Many aspects of cell behaviour are regulated by the interaction of extracellular ligands with specific receptors exposed on the cell surface. The receptors correspond to membrane proteins and expecially glycoproteins. A key event in regulation is the transmission across the surface membrane of the information resulting from receptor-ligand interaction. The activation of lymphocytes by Phaseolus vulgaris phytohaemagglutinin (PHA) provides a convenient experimental model for the study of the molecular basis of receptor-ligand interaction and the molecular consequences of interaction. The receptor mediating lymphocyte activation by PHA is probably a unique glycoprotein which is present to the extent of about 3 X 10(4) molecules/cell. The PHA-receptor complex solubilized in 1% sodium deoxycholate has a molecular size of about 3 X 10(5). The primary event in the activation process is probably an increase in the permeability of the surface membrane to Ca2+. This may be achieved by PHA cross-linking ('patching') the receptors to form a polar channel that permits an influx of Ca2+.", "contents": "Recognition at cell surfaces: phytohaemagglutinin-lymphocyte interaction. Many aspects of cell behaviour are regulated by the interaction of extracellular ligands with specific receptors exposed on the cell surface. The receptors correspond to membrane proteins and expecially glycoproteins. A key event in regulation is the transmission across the surface membrane of the information resulting from receptor-ligand interaction. The activation of lymphocytes by Phaseolus vulgaris phytohaemagglutinin (PHA) provides a convenient experimental model for the study of the molecular basis of receptor-ligand interaction and the molecular consequences of interaction. The receptor mediating lymphocyte activation by PHA is probably a unique glycoprotein which is present to the extent of about 3 X 10(4) molecules/cell. The PHA-receptor complex solubilized in 1% sodium deoxycholate has a molecular size of about 3 X 10(5). The primary event in the activation process is probably an increase in the permeability of the surface membrane to Ca2+. This may be achieved by PHA cross-linking ('patching') the receptors to form a polar channel that permits an influx of Ca2+."}
{"id": "PMID:1814", "title": "Cell communication by periodic cyclic-AMP pulses.", "content": "At the surface of aggregating cells of the slime mould, Dictyostelium discoideum, two different sites interacting with extracellular cAMP are detectable: binding sites and cycl-nucleotide phosphodiesterase. Both sites are developmentally regulated. An adequate stimulus for the chemoreceptor system in D. discoideum is the change of cAMP concentration in time, rather than concentration per se: long-term binding of cAMP causes only short-term response. The system is, consequently, adapted to the recognition of pulses rather than to steady-state concentrations of cAMP. The ce,lls are, nevertheless, able to sense stationary spatial gradients and to respond to them by chemotactic orientation. The possibility is discussed that they do so by transforming spatial concentration changes into temporal ones, using extending pseudopods as sensors. The cAMP recognition system is part of a molecular network involved in the generation of spatio-temporal patterns of cellular activities. This system controls the periodic formation of chemotactic signals and their propagation from cell to cell. The phosphodiesterase limits the duration of the cAMP pulses and thus sharply separates the periods of signalling; the binding sites at the cell surface are supposed to be the chemoreceptors. The control of cellular activities via cAMP receptors can be studied with biochemical techniques with cell suspensions in which spatial inhomogeneities are suppressed by intense stirring, whereas the temporal aspect of the spatiotemporal pattern is preserved. Under these conditions it can be shown that the extracellular cAMP concentration changes periodically, and that the phase of the cellular oscillator can be shifted by external pulses of cAMP. It can also be shown that small cAMP pulses induce a high output of cAMP, which demonstrates signal amplification, a function necessary for a cellular relay system.", "contents": "Cell communication by periodic cyclic-AMP pulses. At the surface of aggregating cells of the slime mould, Dictyostelium discoideum, two different sites interacting with extracellular cAMP are detectable: binding sites and cycl-nucleotide phosphodiesterase. Both sites are developmentally regulated. An adequate stimulus for the chemoreceptor system in D. discoideum is the change of cAMP concentration in time, rather than concentration per se: long-term binding of cAMP causes only short-term response. The system is, consequently, adapted to the recognition of pulses rather than to steady-state concentrations of cAMP. The ce,lls are, nevertheless, able to sense stationary spatial gradients and to respond to them by chemotactic orientation. The possibility is discussed that they do so by transforming spatial concentration changes into temporal ones, using extending pseudopods as sensors. The cAMP recognition system is part of a molecular network involved in the generation of spatio-temporal patterns of cellular activities. This system controls the periodic formation of chemotactic signals and their propagation from cell to cell. The phosphodiesterase limits the duration of the cAMP pulses and thus sharply separates the periods of signalling; the binding sites at the cell surface are supposed to be the chemoreceptors. The control of cellular activities via cAMP receptors can be studied with biochemical techniques with cell suspensions in which spatial inhomogeneities are suppressed by intense stirring, whereas the temporal aspect of the spatiotemporal pattern is preserved. Under these conditions it can be shown that the extracellular cAMP concentration changes periodically, and that the phase of the cellular oscillator can be shifted by external pulses of cAMP. It can also be shown that small cAMP pulses induce a high output of cAMP, which demonstrates signal amplification, a function necessary for a cellular relay system."}
{"id": "PMID:1815", "title": "Recognition of metal cations by biological systems.", "content": "Recognition of metal cations by biological systems can be compared with the geochemical criteria for isomorphous replacement. Biological systems are more highly selective and much more rapid. Methods of maintaining an optimum concentration, including storage and transfer for the essential trace elements, copper and iron, used in some organisms are in part reproducible by coordination chemists while other features have not been reporduced in models. Poisoning can result from a foreign metal taking part in a reaction irreversibly so that the recognition site or molecule is not released. For major nutrients, sodium, potassium, magnesium and calcium, there are similarities to the trace metals in selective uptake but differences qualitatively and quantitatively in biological activity. Compounds selective for potassium replace all the solvation sphere with a symmetrical arrangement of oxygen atoms; those selective for sodium give an asymmetrical environment with retention of a solvent molecule. Experiments with naturally occurring antibiotics and synthetic model compounds have shown that flexibility is an important feature of selectivity and that for transfer or carrier properties there is an optimum (as opposed to a maximum) metal-ligand stability constant. Thallium is taken up instead of potassium and will activate some enzymes; it is suggested that the poisonous characteristics arise because the thallium ion may bind more strongly than potassium to part of a site and then fail to bind additional atoms as required for the biological activity. Criteria for the design of selective complexing agents are given with indications of those which might transfer more than one metal at once.", "contents": "Recognition of metal cations by biological systems. Recognition of metal cations by biological systems can be compared with the geochemical criteria for isomorphous replacement. Biological systems are more highly selective and much more rapid. Methods of maintaining an optimum concentration, including storage and transfer for the essential trace elements, copper and iron, used in some organisms are in part reproducible by coordination chemists while other features have not been reporduced in models. Poisoning can result from a foreign metal taking part in a reaction irreversibly so that the recognition site or molecule is not released. For major nutrients, sodium, potassium, magnesium and calcium, there are similarities to the trace metals in selective uptake but differences qualitatively and quantitatively in biological activity. Compounds selective for potassium replace all the solvation sphere with a symmetrical arrangement of oxygen atoms; those selective for sodium give an asymmetrical environment with retention of a solvent molecule. Experiments with naturally occurring antibiotics and synthetic model compounds have shown that flexibility is an important feature of selectivity and that for transfer or carrier properties there is an optimum (as opposed to a maximum) metal-ligand stability constant. Thallium is taken up instead of potassium and will activate some enzymes; it is suggested that the poisonous characteristics arise because the thallium ion may bind more strongly than potassium to part of a site and then fail to bind additional atoms as required for the biological activity. Criteria for the design of selective complexing agents are given with indications of those which might transfer more than one metal at once."}
{"id": "PMID:1816", "title": "Structure and specificity of antibody molecules.", "content": "The structure of the Fab' fragment of a human myeloma protein (IgG1 (lambda) New) has been determined by X-ray crystallographic analysis to a nominal resolution of 0.2 nm. Each of the structure subunits corresponding to the variable and to the constant homology regions of the light and heavy polypeptide chains contains two irregular beta-sheets which are roughly parallel to each other and surround a tighly packed interior of hydrophobic side chains. The regions of the hypervariable sequences in the light and heavy chains occur in close spatial proximity at one end of the molecule, defining the active site of IgG New. The role of these hypervariable regions in defining the size and shape of the active site of different immunoglobulins is discussed on the basis of the three-dimensional model of Fab' New. Several ligands that bind to the active centre of IgG New have been used to obtain crystalline ligand-Fab' New complexes which were investigated by difference Fourier maps. These studies are analysed in terms of the biological function and specificity of antibodies.", "contents": "Structure and specificity of antibody molecules. The structure of the Fab' fragment of a human myeloma protein (IgG1 (lambda) New) has been determined by X-ray crystallographic analysis to a nominal resolution of 0.2 nm. Each of the structure subunits corresponding to the variable and to the constant homology regions of the light and heavy polypeptide chains contains two irregular beta-sheets which are roughly parallel to each other and surround a tighly packed interior of hydrophobic side chains. The regions of the hypervariable sequences in the light and heavy chains occur in close spatial proximity at one end of the molecule, defining the active site of IgG New. The role of these hypervariable regions in defining the size and shape of the active site of different immunoglobulins is discussed on the basis of the three-dimensional model of Fab' New. Several ligands that bind to the active centre of IgG New have been used to obtain crystalline ligand-Fab' New complexes which were investigated by difference Fourier maps. These studies are analysed in terms of the biological function and specificity of antibodies."}
{"id": "PMID:1817", "title": "Intermolecular forces.", "content": "The nature of molecular interactions is examined. Intermolecular forces are divided into long-range and short-range components; the former operate at distances where the effects of electron exchange are negligible and decrease as an inverse power of the separation. The long-range interactions may be subdividied into electrostatic, induction and dispersion contributions, where the electrostatic component is the interaction of the permanent charge distributions and the others originate in the fluctuations in the distributions. Typical magnitudes of the various contributions are given. The forces between macroscopic bodies are briefly considered, as are the effects of a medium. Some of the manifestations of molecular interactions are discussed.", "contents": "Intermolecular forces. The nature of molecular interactions is examined. Intermolecular forces are divided into long-range and short-range components; the former operate at distances where the effects of electron exchange are negligible and decrease as an inverse power of the separation. The long-range interactions may be subdividied into electrostatic, induction and dispersion contributions, where the electrostatic component is the interaction of the permanent charge distributions and the others originate in the fluctuations in the distributions. Typical magnitudes of the various contributions are given. The forces between macroscopic bodies are briefly considered, as are the effects of a medium. Some of the manifestations of molecular interactions are discussed."}
{"id": "PMID:1818", "title": "Antibody--hapten interactions in solution.", "content": "This paper reports the initial progress in a research programme to identify and obtain the relative orientations, in solution, of the amino acid residues that constitute the combining site of the myeloma protein MOPC 315. This protein has a molecular mass of 150,000, but enzymic digestion yields the Fv fragment of molecular mass 25,000 which still has the combining site intact, as judged by the affinity for dinitrophenyl haptens. Analysis of the e.s.r. spectra of a series of dinitrophenyl spin labelled haptens has allowed the dimensions, rigidity and polarity profile of the combining site to be determined. The combining site is a cleft of overall dimensions 1.1 nm x 0.9 nm x 0.6 nm which has considerable structural rigidity. One of these spin labels has also been used to perturb the n.m.r. spectrum of the Fv and using difference spectroscopy the 270 MHz proton n.m.r. spectrum of the amino acid residues in and around the combining site has been obtained. This spectrum contains only the equivalent of about 30 aromatic and 21 aliphatic protons. Comparison of this difference spectrum with that obtained using a diamagnetic analogue suggests that any conformational changes on hapten binding are mainly localized to the combining site. By the use of (n.m.r.) difference spectroscopy the protons of the three histidine residues in the Fv are observed to titrate with pH and have pKa values of about 8.1, 6.9 and 6.1. The histidine resonances with pKa values 6.9 and 6.1 alter slightly in the presence of haptens and also appear in the spin label difference spectrum, and must therefore be in or near to the combining site. These are assigned to His 102H and His 97L. The existence of lanthanide binding sites on the Fv, necessary for the mapping studies, has been demonstrated by measurements of Gd III water relaxation rates in Fv solutions and also by the changes in the Fv tryptophan fluorescence on addition of Gd III. At pH 5.5 there is one tight binding site for the lanthanides (KD approximately 80 muM) but in the presence of hapten this is weakened 10-20 fold with a reciprocal effect on the hapten binding. Measurements of the Gd III quenching of the e.s.r. spectrum of a spin labelled hapten bound to Fv indicate that the lanthanide site is ca. 1.5 nm from the nitroxide moiety.", "contents": "Antibody--hapten interactions in solution. This paper reports the initial progress in a research programme to identify and obtain the relative orientations, in solution, of the amino acid residues that constitute the combining site of the myeloma protein MOPC 315. This protein has a molecular mass of 150,000, but enzymic digestion yields the Fv fragment of molecular mass 25,000 which still has the combining site intact, as judged by the affinity for dinitrophenyl haptens. Analysis of the e.s.r. spectra of a series of dinitrophenyl spin labelled haptens has allowed the dimensions, rigidity and polarity profile of the combining site to be determined. The combining site is a cleft of overall dimensions 1.1 nm x 0.9 nm x 0.6 nm which has considerable structural rigidity. One of these spin labels has also been used to perturb the n.m.r. spectrum of the Fv and using difference spectroscopy the 270 MHz proton n.m.r. spectrum of the amino acid residues in and around the combining site has been obtained. This spectrum contains only the equivalent of about 30 aromatic and 21 aliphatic protons. Comparison of this difference spectrum with that obtained using a diamagnetic analogue suggests that any conformational changes on hapten binding are mainly localized to the combining site. By the use of (n.m.r.) difference spectroscopy the protons of the three histidine residues in the Fv are observed to titrate with pH and have pKa values of about 8.1, 6.9 and 6.1. The histidine resonances with pKa values 6.9 and 6.1 alter slightly in the presence of haptens and also appear in the spin label difference spectrum, and must therefore be in or near to the combining site. These are assigned to His 102H and His 97L. The existence of lanthanide binding sites on the Fv, necessary for the mapping studies, has been demonstrated by measurements of Gd III water relaxation rates in Fv solutions and also by the changes in the Fv tryptophan fluorescence on addition of Gd III. At pH 5.5 there is one tight binding site for the lanthanides (KD approximately 80 muM) but in the presence of hapten this is weakened 10-20 fold with a reciprocal effect on the hapten binding. Measurements of the Gd III quenching of the e.s.r. spectrum of a spin labelled hapten bound to Fv indicate that the lanthanide site is ca. 1.5 nm from the nitroxide moiety."}
{"id": "PMID:1819", "title": "Molecule--receptor specificity.", "content": "The specificity of binding between small molecules and macromolecular receptors may be studied by comparing theoretically calculated conformational potential energy surfaces of a series of chemically similar molecules which have a range of receptor binding energies and biological activities. In this way essential requirements for binding may be highlighted, including the necessity of the small molecule adopting, or passing through, conformations which are not at energy minima and not found either in the solid state or in aqueous solution. In particular the conformational demands of the adrenergic beta-receptor and histamine H1 receptor are considered.", "contents": "Molecule--receptor specificity. The specificity of binding between small molecules and macromolecular receptors may be studied by comparing theoretically calculated conformational potential energy surfaces of a series of chemically similar molecules which have a range of receptor binding energies and biological activities. In this way essential requirements for binding may be highlighted, including the necessity of the small molecule adopting, or passing through, conformations which are not at energy minima and not found either in the solid state or in aqueous solution. In particular the conformational demands of the adrenergic beta-receptor and histamine H1 receptor are considered."}
{"id": "PMID:1820", "title": "Enzyme substrate and inhibitor interactions.", "content": "An enzyme is designed to bind most tightly to a substrate when it is in the transition state of the reaction which the enzyme catalyses. The consequent reduction of the activation energy of the reaction constitutes the catalytic mechanism. The energetic contributions of different features of the interaction can only be crudely assessed, but they are dominated by entropically driven effects. The binding site of trypsin orients the substrate so that the reacting groups are correctly placed for reaction to occur. Apart from two side chains which take part in chemical steps of the reaction, the enzyme behaves almost as a rigid body. The full binding interactions are only developed when the substrate is in an intermediate stage of the reaction. The tightly bound complexes of trypsin with protein trypsin inhibitors have proved amenable to structural analysis. Enzyme inhibitor interactions, which account for almost 80 kJ mol-1 of interaction energy, are known fairly accurately. The similarity of the two known trypsin inhibitor structures, close to the primary binding site, indicates a high specificity, even for this simple interaction. In cases where no large conformational changes occur the specificity of an enzyme should be predictable from accurate knowledge of its tertiary structure.", "contents": "Enzyme substrate and inhibitor interactions. An enzyme is designed to bind most tightly to a substrate when it is in the transition state of the reaction which the enzyme catalyses. The consequent reduction of the activation energy of the reaction constitutes the catalytic mechanism. The energetic contributions of different features of the interaction can only be crudely assessed, but they are dominated by entropically driven effects. The binding site of trypsin orients the substrate so that the reacting groups are correctly placed for reaction to occur. Apart from two side chains which take part in chemical steps of the reaction, the enzyme behaves almost as a rigid body. The full binding interactions are only developed when the substrate is in an intermediate stage of the reaction. The tightly bound complexes of trypsin with protein trypsin inhibitors have proved amenable to structural analysis. Enzyme inhibitor interactions, which account for almost 80 kJ mol-1 of interaction energy, are known fairly accurately. The similarity of the two known trypsin inhibitor structures, close to the primary binding site, indicates a high specificity, even for this simple interaction. In cases where no large conformational changes occur the specificity of an enzyme should be predictable from accurate knowledge of its tertiary structure."}
{"id": "PMID:1822", "title": "The thermal transition of brain soluble proteins.", "content": "Soluble rat brain proteins undergo a thermal reversible denaturation in the range of 20 degrees C -65 degrees C. The thermal transition as studied in 0.25 M sucrose solution, is associated with changes in the proteins ionization capacity by the lowering of the isoionic solution pHfrom a value of 6.95 at 20 degrees C to 6.55 at 65 degrees C. The apparent enthalpy change delta H at the transition temperature (t=50 degrees C) is about 34 Kcal, heat capacity delta Cp about 1.75 Kcal, and apparent entrophy change deltaS 100 e.u. The data suggest that the thermal transition is predominantly a two-state process. A prolonged keeping of the protein solution at the increased temperature produces a partial reversibility of thermal transitions by a lowering of 5-HT cations fixing on the protein molecule.", "contents": "The thermal transition of brain soluble proteins. Soluble rat brain proteins undergo a thermal reversible denaturation in the range of 20 degrees C -65 degrees C. The thermal transition as studied in 0.25 M sucrose solution, is associated with changes in the proteins ionization capacity by the lowering of the isoionic solution pHfrom a value of 6.95 at 20 degrees C to 6.55 at 65 degrees C. The apparent enthalpy change delta H at the transition temperature (t=50 degrees C) is about 34 Kcal, heat capacity delta Cp about 1.75 Kcal, and apparent entrophy change deltaS 100 e.u. The data suggest that the thermal transition is predominantly a two-state process. A prolonged keeping of the protein solution at the increased temperature produces a partial reversibility of thermal transitions by a lowering of 5-HT cations fixing on the protein molecule."}
{"id": "PMID:1824", "title": "Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment.", "content": "Seven of nine depressed patients experienced a 4.3-fold increase in rated euphoria and activation following 30 mg d-amphetamine in a replicated dose, double blind study. d-Amphetamine was 2 to 2.3-fold more effective in producing activation, euphoria, and antidepressant effects than the same dose of l-amphetamine. Co-treatment with lithium carbonate produced a 60% (P less than 0.001) attenuation of the activation and euphoria responses to d-amphetamine. The responses to l-amphetamine were almost completely abolished by lithium. This study raises the possibility of lithium carbonate use as an adjunct in the treatment of amphetamine addiction.", "contents": "Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment. Seven of nine depressed patients experienced a 4.3-fold increase in rated euphoria and activation following 30 mg d-amphetamine in a replicated dose, double blind study. d-Amphetamine was 2 to 2.3-fold more effective in producing activation, euphoria, and antidepressant effects than the same dose of l-amphetamine. Co-treatment with lithium carbonate produced a 60% (P less than 0.001) attenuation of the activation and euphoria responses to d-amphetamine. The responses to l-amphetamine were almost completely abolished by lithium. This study raises the possibility of lithium carbonate use as an adjunct in the treatment of amphetamine addiction."}
{"id": "PMID:1830", "title": "Some metabolic approaches to improving myocardial performance during cardiac hypoxia.", "content": "Four possible metabolic approaches to improving cardiac function in the presence of myocardial hypoxia have been considered. 1. It appears that there is increasing evidence which suggests that free fatty acids are harmful to the ischemic heart. 2. Although it has been demonstrated that Krebs cycle intermediates can result in anaerobic energy formation by the mitochondria, and under certain extreme conditions can lead to improved performance of the heart, the potential for a physiologically important effect of this approach is probably limited. 3. The protection of the ischemic or hypoxic heart by alkalosis may be a feasible approach. The major beneficial effect appears to be exerted through more efficient conversion of energy that is already available to contractile performance rather than by increasing energy supply. 4. There appears to be some real potential for improving cardiac energy delivery via the glycolytic pathway. Calculations based on isolated rat heart studies indicate that, at 50% oxygenation, glycolytic ATP generation could totally correct for the deficit in mitochondrial ATP formation. Therefore, it is in the area of overcoming the inhibition of glycolytic ATP formation and tapping this potential metabolic pathway that energy delivery may be restored toward normal in the hypoxic and perhaps the borderline zone of underperfusion in the ischemic heart. The problem of the ischemic inhibition of glycolysis may partially be overcome by creating extracellular alkalosis, but this presumption will have to be tested.", "contents": "Some metabolic approaches to improving myocardial performance during cardiac hypoxia. Four possible metabolic approaches to improving cardiac function in the presence of myocardial hypoxia have been considered. 1. It appears that there is increasing evidence which suggests that free fatty acids are harmful to the ischemic heart. 2. Although it has been demonstrated that Krebs cycle intermediates can result in anaerobic energy formation by the mitochondria, and under certain extreme conditions can lead to improved performance of the heart, the potential for a physiologically important effect of this approach is probably limited. 3. The protection of the ischemic or hypoxic heart by alkalosis may be a feasible approach. The major beneficial effect appears to be exerted through more efficient conversion of energy that is already available to contractile performance rather than by increasing energy supply. 4. There appears to be some real potential for improving cardiac energy delivery via the glycolytic pathway. Calculations based on isolated rat heart studies indicate that, at 50% oxygenation, glycolytic ATP generation could totally correct for the deficit in mitochondrial ATP formation. Therefore, it is in the area of overcoming the inhibition of glycolytic ATP formation and tapping this potential metabolic pathway that energy delivery may be restored toward normal in the hypoxic and perhaps the borderline zone of underperfusion in the ischemic heart. The problem of the ischemic inhibition of glycolysis may partially be overcome by creating extracellular alkalosis, but this presumption will have to be tested."}
{"id": "PMID:1831", "title": "Factors influencing tolerance of cardiac muscle to hypoxia.", "content": "The effects of isoproterenol, glucose, and pH on the responses of isolated rat cardiac muscle to hypoxia (95% N2, 5% CO2) were examined while the muscles were contracting isometrically 12 times a minute at 28 degrees C. In the presence of 5.5 mM glucose, 10(-5) M isoproterenol and alkaline pH (7.8) improved the performance of cardiac muscle during early hypoxia. This was followed by a premature decline in developed tension, and contracture appeared. Recovery of function following reoxygenation with 95% O2 and 5% CO2 after a 60-min period of hypoxia was poor. Acid pH (6.8) resulted in an early decline of mechanical activity during hypoxia; but contracture did not appear, and full recovery of developed tension was seen upon reoxygenation after 60 min of hypoxia. When 22 mM glucose was used as substrate, the early responses to hypoxia were not altered; but late performance was improved, contracture did not appear, and full recovery after 60 min of hypoxia was seen. If additional glucose was added to the bath after 30 min of hypoxia (concentration 22 mM), little effect on developed tension was evident; but contracture diminished and recovery after 60 min of hypoxia was improved. Addition of 22 mM glucose allowed isoproterenol to exert its inotropic effect in the absence of late deleterious changes. The data support the concept that factors tending to increase the utilization of limited stores of anaerobic substrate during hypoxia facilitate deterioration. By increasing exogenous glucose, the support of inotropic activity without late adverse effects appears possible, and recovery is improved upon reoxygenation.", "contents": "Factors influencing tolerance of cardiac muscle to hypoxia. The effects of isoproterenol, glucose, and pH on the responses of isolated rat cardiac muscle to hypoxia (95% N2, 5% CO2) were examined while the muscles were contracting isometrically 12 times a minute at 28 degrees C. In the presence of 5.5 mM glucose, 10(-5) M isoproterenol and alkaline pH (7.8) improved the performance of cardiac muscle during early hypoxia. This was followed by a premature decline in developed tension, and contracture appeared. Recovery of function following reoxygenation with 95% O2 and 5% CO2 after a 60-min period of hypoxia was poor. Acid pH (6.8) resulted in an early decline of mechanical activity during hypoxia; but contracture did not appear, and full recovery of developed tension was seen upon reoxygenation after 60 min of hypoxia. When 22 mM glucose was used as substrate, the early responses to hypoxia were not altered; but late performance was improved, contracture did not appear, and full recovery after 60 min of hypoxia was seen. If additional glucose was added to the bath after 30 min of hypoxia (concentration 22 mM), little effect on developed tension was evident; but contracture diminished and recovery after 60 min of hypoxia was improved. Addition of 22 mM glucose allowed isoproterenol to exert its inotropic effect in the absence of late deleterious changes. The data support the concept that factors tending to increase the utilization of limited stores of anaerobic substrate during hypoxia facilitate deterioration. By increasing exogenous glucose, the support of inotropic activity without late adverse effects appears possible, and recovery is improved upon reoxygenation."}
{"id": "PMID:1832", "title": "Effects of pH and pCO2 on performance of ischemic myocardium.", "content": "Contractile performance of ischemic feline myocardium was evaluated under conditions of selective changes in perfusate in pH and pCO2. A substantial increase in myocardial performance was noted when the pCO2 was lowered at constant pH, and depression of performance was noted when the pCO2 was increased at constant pH. Perfusate acidosis at constant pCO2 resulted in depression of performance and decreased performance only after 20 min of exposure. Alkalosis did not increase performance and decreased performance transiently during mild ischemia. These studies suggest that performance of myocardium during ischemia is closely related to tissue pCO2 and is minimally related to the level of extracellular pH.", "contents": "Effects of pH and pCO2 on performance of ischemic myocardium. Contractile performance of ischemic feline myocardium was evaluated under conditions of selective changes in perfusate in pH and pCO2. A substantial increase in myocardial performance was noted when the pCO2 was lowered at constant pH, and depression of performance was noted when the pCO2 was increased at constant pH. Perfusate acidosis at constant pCO2 resulted in depression of performance and decreased performance only after 20 min of exposure. Alkalosis did not increase performance and decreased performance transiently during mild ischemia. These studies suggest that performance of myocardium during ischemia is closely related to tissue pCO2 and is minimally related to the level of extracellular pH."}
{"id": "PMID:1833", "title": "Effects of inhalation anesthetics on cardiac function and metabolism in the intact dog.", "content": "In healthy, closed-chest dogs, dose-dependent depression of ventricular function was produced by the anesthetics halothane, methoxyflurane, and fluroxene, as evidence by decreases in left venticular stroke volume, stroke work, dP/dt, and an increased enddiastolic pressure. Myocardial blood flow and oxygen consumption decreased concomitantly and were correlated with aortic blood pressure decreases. There was no change in myocardial lactate extraction with halothane and methoxyflurane, suggesting that myocardial  oxygenation was adequate in spite of the decrease in blood flow. However, even with marked increases in arterial lactate concentration during fluroxene anesthesia, extraction did not chance and, in fact, tended to decrease. The hemodynamic effects of halothane and methoxyflurane are similar to those previously reported in man, but those of fluroxene are different. Consequently, clinical speculation from these results is not justified at this time.", "contents": "Effects of inhalation anesthetics on cardiac function and metabolism in the intact dog. In healthy, closed-chest dogs, dose-dependent depression of ventricular function was produced by the anesthetics halothane, methoxyflurane, and fluroxene, as evidence by decreases in left venticular stroke volume, stroke work, dP/dt, and an increased enddiastolic pressure. Myocardial blood flow and oxygen consumption decreased concomitantly and were correlated with aortic blood pressure decreases. There was no change in myocardial lactate extraction with halothane and methoxyflurane, suggesting that myocardial  oxygenation was adequate in spite of the decrease in blood flow. However, even with marked increases in arterial lactate concentration during fluroxene anesthesia, extraction did not chance and, in fact, tended to decrease. The hemodynamic effects of halothane and methoxyflurane are similar to those previously reported in man, but those of fluroxene are different. Consequently, clinical speculation from these results is not justified at this time."}
{"id": "PMID:1834", "title": "Tissue water and pH in experimental primary cardiomyopathy induced by isoproterenol in frog.", "content": "Acute aneurysms and other morphologically defined cardiac lesions were produced in frogs by isoproterenol (IPR) as previously described. Samples from lesions verified in vivo and from macroscopically normal ventricular areas, together with samples from nontreated control animals, were analyzed for total water content, inulin space, pHe, and pHi by using DMO-14C and inulin-3H. Total cardiac tissue water content was increased in all types of lesions after IPR injection. The highest content was found in bulging, noncontractile aneurysms. Inulin space was enlarged in all heart muscle specimens from IPR-treated animals, including those without macroscopically visible lesions. Those specimens with aneurysms showed the greatest degree of enlargement. The (pHe-pHi) did not differ between injected and noninjected animals, and the noncontractile samples from aneurysms did not differ from other lesions and macroscopically intact areas. In IPR-injected animals, there was no difference in pHi between macroscopically damaged and nondamaged segments of ventricle wall. On comparing these animals to controls, however, a slight shift to the alkaline side for both pHi and pHe was observed. The (pHe-pHi) was higher in skeletal muscle than in heart muscle in both IPR-treated and nontreated animals. Tissue water increased in skeletal muscle after IPR injection, reflecting a change of intracellular water as inulin space was maintained.", "contents": "Tissue water and pH in experimental primary cardiomyopathy induced by isoproterenol in frog. Acute aneurysms and other morphologically defined cardiac lesions were produced in frogs by isoproterenol (IPR) as previously described. Samples from lesions verified in vivo and from macroscopically normal ventricular areas, together with samples from nontreated control animals, were analyzed for total water content, inulin space, pHe, and pHi by using DMO-14C and inulin-3H. Total cardiac tissue water content was increased in all types of lesions after IPR injection. The highest content was found in bulging, noncontractile aneurysms. Inulin space was enlarged in all heart muscle specimens from IPR-treated animals, including those without macroscopically visible lesions. Those specimens with aneurysms showed the greatest degree of enlargement. The (pHe-pHi) did not differ between injected and noninjected animals, and the noncontractile samples from aneurysms did not differ from other lesions and macroscopically intact areas. In IPR-injected animals, there was no difference in pHi between macroscopically damaged and nondamaged segments of ventricle wall. On comparing these animals to controls, however, a slight shift to the alkaline side for both pHi and pHe was observed. The (pHe-pHi) was higher in skeletal muscle than in heart muscle in both IPR-treated and nontreated animals. Tissue water increased in skeletal muscle after IPR injection, reflecting a change of intracellular water as inulin space was maintained."}
{"id": "PMID:1844", "title": "Normal arterial blood gases during experimental hypertriglyceridemia in the rat.", "content": "The possible effect of high concentrations of plasma triglycerides on arterial oxygen tension was investigated in rats by infusion of lymph chylomicrons or a soybean oil emulsion (Intralipid). Mean triglyceride concentrations were raised from 130 to 1454 mg/100 ml without statistically significant change in arterial oxygen tension, oxygen saturation, carbon dioxide tension, or pH. The small reduction in arterial oxygen tension, content, or saturation observed in earlier studies may have been due to inadequate stabilization of fat emulsion then available for intravenous use. The present data suggest that high concentrations of plasma triglycerides produced by infusion of chylomicrons or Intralipid do not affect arterial blood gases in the normal rat.", "contents": "Normal arterial blood gases during experimental hypertriglyceridemia in the rat. The possible effect of high concentrations of plasma triglycerides on arterial oxygen tension was investigated in rats by infusion of lymph chylomicrons or a soybean oil emulsion (Intralipid). Mean triglyceride concentrations were raised from 130 to 1454 mg/100 ml without statistically significant change in arterial oxygen tension, oxygen saturation, carbon dioxide tension, or pH. The small reduction in arterial oxygen tension, content, or saturation observed in earlier studies may have been due to inadequate stabilization of fat emulsion then available for intravenous use. The present data suggest that high concentrations of plasma triglycerides produced by infusion of chylomicrons or Intralipid do not affect arterial blood gases in the normal rat."}
{"id": "PMID:1845", "title": "Diagnosis of liver diseases by laboratory results and discriminant analysis. Identification of best combinations of laboratory tests.", "content": "Patients with different liver diseases were studied by discriminant analysis. Groups of patients classified mainly on the basis of liver biopsy findings showed functional differences which permitted a consistent reclassification by discriminant functions using laboratory results. Optimal combinations of laboratory tests for the separation of liver diseases were defined. Different combinations were found, dependent on the subsets of liver diseases studied.", "contents": "Diagnosis of liver diseases by laboratory results and discriminant analysis. Identification of best combinations of laboratory tests. Patients with different liver diseases were studied by discriminant analysis. Groups of patients classified mainly on the basis of liver biopsy findings showed functional differences which permitted a consistent reclassification by discriminant functions using laboratory results. Optimal combinations of laboratory tests for the separation of liver diseases were defined. Different combinations were found, dependent on the subsets of liver diseases studied."}
{"id": "PMID:1846", "title": "Survival of rats subjected to acute anemia at different levels of erythrocyte 2,3-diphosphoglycerate.", "content": "An experimental procedure was worked out in which rats were subjected to an exchange of erythrocytes, followed by acute anemia by means of hemodilution. One group of rats received erythrocytes with a high concentration of 2,3-diphosphoglycerate (DPG), and the other group was given erythrocytes with a low DPG concentration. The survival rate was equal in the two groups. Irrespective of DPG concentration, the rats whose hemoglobin concentration reached the lowest level died. The rats that died were also more acidotic than the others. The results indicate that the hemoglobin concentration and the pH value were more important determinants for survival than the DPG concentrations.", "contents": "Survival of rats subjected to acute anemia at different levels of erythrocyte 2,3-diphosphoglycerate. An experimental procedure was worked out in which rats were subjected to an exchange of erythrocytes, followed by acute anemia by means of hemodilution. One group of rats received erythrocytes with a high concentration of 2,3-diphosphoglycerate (DPG), and the other group was given erythrocytes with a low DPG concentration. The survival rate was equal in the two groups. Irrespective of DPG concentration, the rats whose hemoglobin concentration reached the lowest level died. The rats that died were also more acidotic than the others. The results indicate that the hemoglobin concentration and the pH value were more important determinants for survival than the DPG concentrations."}
{"id": "PMID:1847", "title": "The influence of bacterial superinfection on the clinical course of influenza. Studies from the influenza epidemics in Stockholm during the winters 1969-70 and 1971-72.", "content": "During two epidemics of influenza A infection in Stockholm 1969-72, 249 cases were selected for a study on the effect of bacterial superinfection. Bacterial involvement was demonstrated through cultures and serologic reactions. The occurrence of C-reactive protein in increased amount in serum was significantly more common in the group which had the strongest indication of bacterial infection. An increased duration of fever, and a higher incidence of pneumonia, leukocytosis and erythrocyte sedimentation rate over 50 mm/l h was also the rule in cases with bacterial involvement. During both epidemics the bacteria most often involved were pneumococci.", "contents": "The influence of bacterial superinfection on the clinical course of influenza. Studies from the influenza epidemics in Stockholm during the winters 1969-70 and 1971-72. During two epidemics of influenza A infection in Stockholm 1969-72, 249 cases were selected for a study on the effect of bacterial superinfection. Bacterial involvement was demonstrated through cultures and serologic reactions. The occurrence of C-reactive protein in increased amount in serum was significantly more common in the group which had the strongest indication of bacterial infection. An increased duration of fever, and a higher incidence of pneumonia, leukocytosis and erythrocyte sedimentation rate over 50 mm/l h was also the rule in cases with bacterial involvement. During both epidemics the bacteria most often involved were pneumococci."}
{"id": "PMID:1848", "title": "Evaluation of the antibiotic effect of treatment of maxillary sinusitis.", "content": "As the effect of antibiotic treatment of maxillary sinusitis has been questioned, the elimination of bacteria from sinus secretions was studied during antibiotic treatment. Penicillin V, azidocillin, tetracycline or doxycycline was administered to 54 patients with maxillary sinusitis. Samples of sinus secretion were aspirated both before treatment and 2-3 days after the onset of treatment. When the antibiotic concentration was below the upper limit of MIC for sensitivity group 1, bacterial growth was present in practically all samples. When the antibiotic concentration equalled or was above this limit, there was no bacterial growth in about half of the samples. A prerequisite for antibiotic effect--elimination of bacteria--is that the antibiotic concentration is well above the MIC of the bacteria at the site of infection. The choice between bactericidal or bacteriostatic antibiotics appeared unimportant. Bacterial survival in the maxillary sinus despite a high antibiotic concentration in the sinus illustrates that MIC values determined in the laboratory do not always mirror the sensitivity of bacteria to antibiotics in vivo.", "contents": "Evaluation of the antibiotic effect of treatment of maxillary sinusitis. As the effect of antibiotic treatment of maxillary sinusitis has been questioned, the elimination of bacteria from sinus secretions was studied during antibiotic treatment. Penicillin V, azidocillin, tetracycline or doxycycline was administered to 54 patients with maxillary sinusitis. Samples of sinus secretion were aspirated both before treatment and 2-3 days after the onset of treatment. When the antibiotic concentration was below the upper limit of MIC for sensitivity group 1, bacterial growth was present in practically all samples. When the antibiotic concentration equalled or was above this limit, there was no bacterial growth in about half of the samples. A prerequisite for antibiotic effect--elimination of bacteria--is that the antibiotic concentration is well above the MIC of the bacteria at the site of infection. The choice between bactericidal or bacteriostatic antibiotics appeared unimportant. Bacterial survival in the maxillary sinus despite a high antibiotic concentration in the sinus illustrates that MIC values determined in the laboratory do not always mirror the sensitivity of bacteria to antibiotics in vivo."}
{"id": "PMID:1849", "title": "Roentgenological findings in cryptorchidism.", "content": "Intravenous urography of 78 cryptorchid boys revealed no clinically significant upper urinary tract anomalies. Two boys had a rotated kidney and 2 others a double renal pelvis. One boy had previously been operated upon because of hydronephrosis. There thus appears to be no reason for routine intravenous urography of cryptorchid boys. Forty-two per cent of the boys had spina bifida occulta in the lumbar and sacral spine. One case of asymptomatic congenital cardiac disease was discovered at routine chest X-ray.", "contents": "Roentgenological findings in cryptorchidism. Intravenous urography of 78 cryptorchid boys revealed no clinically significant upper urinary tract anomalies. Two boys had a rotated kidney and 2 others a double renal pelvis. One boy had previously been operated upon because of hydronephrosis. There thus appears to be no reason for routine intravenous urography of cryptorchid boys. Forty-two per cent of the boys had spina bifida occulta in the lumbar and sacral spine. One case of asymptomatic congenital cardiac disease was discovered at routine chest X-ray."}
{"id": "PMID:1850", "title": "Semen cahracteristics before and after ligation of the left internal spermatic veins in men with varicocele.", "content": "The semen from 20 men with varicocele was studied before and after surgical correction of the varicocele. The effect on sperm quality was only marginal and could not explain the fairly high conception rate (20%) after operation. The recommendation that varicocele in men with long-term infertility should be eliminated by ligation of the internal spermatic veins is still justified despite the absence of positive effects on sperm quality.", "contents": "Semen cahracteristics before and after ligation of the left internal spermatic veins in men with varicocele. The semen from 20 men with varicocele was studied before and after surgical correction of the varicocele. The effect on sperm quality was only marginal and could not explain the fairly high conception rate (20%) after operation. The recommendation that varicocele in men with long-term infertility should be eliminated by ligation of the internal spermatic veins is still justified despite the absence of positive effects on sperm quality."}
{"id": "PMID:1853", "title": "Plasma potassium and insulin during extracorporeal circulation using a glucose-containing pump prime.", "content": "In order to investigate the possible relationship between a glucose-containing pump prime and changes in plasma potassium during extracorporeal circulation, determinations were made of blood glucose and plasma insulin, potassium, and magnesium in 18 subjects undergoing open-heart surgery. In 6 of the patients, the same parameters had been measured during a pre-operative glucose tolerance test. It was found that the elimination of glucose was considerably impaired during extracorporeal circulation, in spite of high insulin levels. During the first minutes of extracorporeal circulation, plasma potassium fell more than during the glucose tolerance test, in spite of comparable insulin levels. It is concluded that changes in plasma potassium during extracorporeal circulation do not reflect insulin activity to any noticeable extent.", "contents": "Plasma potassium and insulin during extracorporeal circulation using a glucose-containing pump prime. In order to investigate the possible relationship between a glucose-containing pump prime and changes in plasma potassium during extracorporeal circulation, determinations were made of blood glucose and plasma insulin, potassium, and magnesium in 18 subjects undergoing open-heart surgery. In 6 of the patients, the same parameters had been measured during a pre-operative glucose tolerance test. It was found that the elimination of glucose was considerably impaired during extracorporeal circulation, in spite of high insulin levels. During the first minutes of extracorporeal circulation, plasma potassium fell more than during the glucose tolerance test, in spite of comparable insulin levels. It is concluded that changes in plasma potassium during extracorporeal circulation do not reflect insulin activity to any noticeable extent."}
{"id": "PMID:1854", "title": "Construction and evaluation of a simple membrane oxygenator for small organ perfusion.", "content": "A simple membrane oxygenator for isolated organ perfusion is described. The membrane employed consisted of an ordinary silicone rubber tubing, 2 mm internal diameter, 0.3 mm wall thickness, the length of the tubing varying according to the required gas transfer. When describing the capacity of the oxygenator, it was found that the maximum gas transfer rate per unit membrane surface was an inadequate measure, since this would vary with both flow rate through the oxygenator and the gas binding capacity of the perfusate. The following formula for the function describing the relation between maximally possible change in gas concentration in the perfusate (C), flow rate (F) and actual change in gas concentration in the perfusate (U) was proposed: U=C-e(-bF), b being a constant specific for the gas and the membrane. This formula was tested by a series of in vitro experiments and proved to give a valid description of the capacity of the oxygenator. It was also found that carbon dioxide was always more easily transferred than oxygen, so that oxygen transfer capcity was the limiting factor in the use of the oxygenator. To facilitate the construction of the right size membrane, a nomogram was constructed for oxygen transfer.", "contents": "Construction and evaluation of a simple membrane oxygenator for small organ perfusion. A simple membrane oxygenator for isolated organ perfusion is described. The membrane employed consisted of an ordinary silicone rubber tubing, 2 mm internal diameter, 0.3 mm wall thickness, the length of the tubing varying according to the required gas transfer. When describing the capacity of the oxygenator, it was found that the maximum gas transfer rate per unit membrane surface was an inadequate measure, since this would vary with both flow rate through the oxygenator and the gas binding capacity of the perfusate. The following formula for the function describing the relation between maximally possible change in gas concentration in the perfusate (C), flow rate (F) and actual change in gas concentration in the perfusate (U) was proposed: U=C-e(-bF), b being a constant specific for the gas and the membrane. This formula was tested by a series of in vitro experiments and proved to give a valid description of the capacity of the oxygenator. It was also found that carbon dioxide was always more easily transferred than oxygen, so that oxygen transfer capcity was the limiting factor in the use of the oxygenator. To facilitate the construction of the right size membrane, a nomogram was constructed for oxygen transfer."}
{"id": "PMID:1855", "title": "The influence of arm ischaemia and arm hyperaemia on subclavian and vertebral artery blood flow in patients with occlusive disease of the subclavian artery and the brachiocephalic trunk. A peroperative study.", "content": "A peroperative study of blood flow and flow direction was performed in series of patients with occlusive disease of the subclavian artery. Particular attention was focused on the flow variations caused by arm ischaemia and postischaemic hyperaemia and on the effect of injection of a vasodilator into the distal subclavian artery. The effect on blood flow and flow direction was measured with the aid of an electromagnetic flowmeter. During arm ischaemia induced by an inflated cuff on the arm, the subclavian flow diminished, as did the vertebral artery flow when it was retrograde. If the vertebral artery flow was anterograde, it increased during arm ischaemia. The postischaemic hyperaemia caused an increase of the subclavian flow and of reversed vertebral flow. If the vertebral flow was anterograde, it diminished during the postischaemic hyperaemia. Similar findings were obtained with intra-arterial injection of a vasodilator. The large amount of blood flow passing through the vertebral artery, as well as the flow variations caused by reactive arm hyperaemia, emphasize the role of this artery as a collateral vessel to the upper limb in cases of the subclavian steal phenomenon.", "contents": "The influence of arm ischaemia and arm hyperaemia on subclavian and vertebral artery blood flow in patients with occlusive disease of the subclavian artery and the brachiocephalic trunk. A peroperative study. A peroperative study of blood flow and flow direction was performed in series of patients with occlusive disease of the subclavian artery. Particular attention was focused on the flow variations caused by arm ischaemia and postischaemic hyperaemia and on the effect of injection of a vasodilator into the distal subclavian artery. The effect on blood flow and flow direction was measured with the aid of an electromagnetic flowmeter. During arm ischaemia induced by an inflated cuff on the arm, the subclavian flow diminished, as did the vertebral artery flow when it was retrograde. If the vertebral artery flow was anterograde, it increased during arm ischaemia. The postischaemic hyperaemia caused an increase of the subclavian flow and of reversed vertebral flow. If the vertebral flow was anterograde, it diminished during the postischaemic hyperaemia. Similar findings were obtained with intra-arterial injection of a vasodilator. The large amount of blood flow passing through the vertebral artery, as well as the flow variations caused by reactive arm hyperaemia, emphasize the role of this artery as a collateral vessel to the upper limb in cases of the subclavian steal phenomenon."}
{"id": "PMID:1856", "title": "Spectroscopic observation of acid sulfate in atmospheric particulate samples.", "content": "Infrared spectra of time- and size-classified atmospheric particulate samples collected with a inertial impactor reveal the presence of acid sulfate in the submicrometer-sized fraction. Although the degree of acidity is highly variable with time, the acidic nature of the particles is observed at all times of the day and may persist for several days in urban areas.", "contents": "Spectroscopic observation of acid sulfate in atmospheric particulate samples. Infrared spectra of time- and size-classified atmospheric particulate samples collected with a inertial impactor reveal the presence of acid sulfate in the submicrometer-sized fraction. Although the degree of acidity is highly variable with time, the acidic nature of the particles is observed at all times of the day and may persist for several days in urban areas."}
{"id": "PMID:1857", "title": "Specific effects of neurotransmitter antagonists on ganglion cells in rabbit retina.", "content": "Directionally sensitive ganglion cells in rabbit retina lose their directional sensitivity when picrotoxin, an antagonist of the inhibitory neurotransmitter gamma-aminobutyric acid, is infused into the retinal blood supply. Strychnine, an antagonist of glycine, does not produce this effect. Other receptive field types are affected by strychnine but not picrotoxin. Inhibitory transmitters therefore have specific functions in information processing in the retina.", "contents": "Specific effects of neurotransmitter antagonists on ganglion cells in rabbit retina. Directionally sensitive ganglion cells in rabbit retina lose their directional sensitivity when picrotoxin, an antagonist of the inhibitory neurotransmitter gamma-aminobutyric acid, is infused into the retinal blood supply. Strychnine, an antagonist of glycine, does not produce this effect. Other receptive field types are affected by strychnine but not picrotoxin. Inhibitory transmitters therefore have specific functions in information processing in the retina."}
{"id": "PMID:1858", "title": "Vascular and brain dopamine beta-hydroxylase activity in young spontaneously hypertensive rats.", "content": "Dopamine beta-hydroxylase activity was higher in mesenteric vessels, adrenal glands, and serum of 3-week-old spontaneously hypertensive rats but lower in the locus coeruleus than it was in the control Wistar-Kyoto rats. The results support the concept that the nervous system is an important regulator of blood pressure.", "contents": "Vascular and brain dopamine beta-hydroxylase activity in young spontaneously hypertensive rats. Dopamine beta-hydroxylase activity was higher in mesenteric vessels, adrenal glands, and serum of 3-week-old spontaneously hypertensive rats but lower in the locus coeruleus than it was in the control Wistar-Kyoto rats. The results support the concept that the nervous system is an important regulator of blood pressure."}
{"id": "PMID:1859", "title": "Protein purification: adsorption chromatography on controlled pore glass with the use of chaotropic buffers.", "content": "Chromatography on controlled pore glass in combination with chaotropic buffers makes possible, in a single step, protein purifications of several hundredfold. The new emphasis is on highly selective controllable adsorption. The method is useful for the purification and concentration of proteins from large volumes of complex media and for the purification of proteins that are poorly soluble or tend to aggregate in aqueous solution D-(-)-Beta-Hydroxybutyrate dehydrogenase, a mitochondrial membrane-bound protein, several soluble proteins, and staphylococcal alpha toxin, which can be purified directly from large volumes of culture medium, are used to illustrate the method.", "contents": "Protein purification: adsorption chromatography on controlled pore glass with the use of chaotropic buffers. Chromatography on controlled pore glass in combination with chaotropic buffers makes possible, in a single step, protein purifications of several hundredfold. The new emphasis is on highly selective controllable adsorption. The method is useful for the purification and concentration of proteins from large volumes of complex media and for the purification of proteins that are poorly soluble or tend to aggregate in aqueous solution D-(-)-Beta-Hydroxybutyrate dehydrogenase, a mitochondrial membrane-bound protein, several soluble proteins, and staphylococcal alpha toxin, which can be purified directly from large volumes of culture medium, are used to illustrate the method."}
{"id": "PMID:1860", "title": "[Determination of barbiturates from biological material].", "content": "A trace quantitative analysis of barbiturates has been carried out in blood, urine, organs and in gastric and intestinal concents. The amount of sample required for analysis is very small [approximately 400 mul blood]. Extraction is carried out four times with the mixture of acetone and either 1:1]. The preparation of columns, packing and standards has been described. The device used for the analyses [Chrom 3] is furnished with an adjusted feeding block preventing the decomposition of samples in the doser. The column temperature is 190 degrees C, the column packing is Chromaton N-AW-DMCS coated with 3% NPGS and 0.75% trimer acid, detector FID.", "contents": "[Determination of barbiturates from biological material]. A trace quantitative analysis of barbiturates has been carried out in blood, urine, organs and in gastric and intestinal concents. The amount of sample required for analysis is very small [approximately 400 mul blood]. Extraction is carried out four times with the mixture of acetone and either 1:1]. The preparation of columns, packing and standards has been described. The device used for the analyses [Chrom 3] is furnished with an adjusted feeding block preventing the decomposition of samples in the doser. The column temperature is 190 degrees C, the column packing is Chromaton N-AW-DMCS coated with 3% NPGS and 0.75% trimer acid, detector FID."}
{"id": "PMID:1862", "title": "The mechanism of the inhibition of iron absorption by tea.", "content": "Previous human studies have shown that drinking tea during meals significantly inhibits the absorption of both food iron and medicinal iron. This study provides evidence from experiments with rats that the tannins in the tea are responsible for the inhibition, probably by forming non-absorbable complexes with the iron within the intestinal lumen. The molar ratio of tannin: iron is dependent on the pH, being 1:1 at pH 2,0 2:1 at pH 5,5 and 3:1 at pH 8,0. Since tannins are present in many vegetable foods the formation of such complexes may be a factor in the poor availability for absorption of much food iron.", "contents": "The mechanism of the inhibition of iron absorption by tea. Previous human studies have shown that drinking tea during meals significantly inhibits the absorption of both food iron and medicinal iron. This study provides evidence from experiments with rats that the tannins in the tea are responsible for the inhibition, probably by forming non-absorbable complexes with the iron within the intestinal lumen. The molar ratio of tannin: iron is dependent on the pH, being 1:1 at pH 2,0 2:1 at pH 5,5 and 3:1 at pH 8,0. Since tannins are present in many vegetable foods the formation of such complexes may be a factor in the poor availability for absorption of much food iron."}
{"id": "PMID:1863", "title": "An investigation into the hepatic cytochrome P-450 catalysed metabolism of the anaesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether).", "content": "The role of the different cytochromes P-450 in the metabolism of the anaesthetic agent fluroxene, and the mechanism of production of toxic effects seen after pre-treatment of the animals with pehnobarbital prior to anaesthesia, have been investigated. Male rats were anaesthetized with fluroxene, or with 2,2,2-trifluroethyl ethyl ether, or with ethyl vinyl ether in an attempt to ascertain the in vivo toxic effects of the three anaesthetic agents. The resultant hepatic histology is reported. A study of the binding and metabolism of fluroxene by isolated rat hepatic microsomes was also made. We conclude that it is elevated levels of cytochrome P-450 which potentiate the toxicity of fluroxene anaesthesia in phenobarbital treated animals and that cytochrome P-448 does not bind or metabolize fluroxene. The potential toxicity of the fluroxene molecule is considered to reside in the trifluoroethyl moiety, while the vinyl group of fluroxene appears to play a role in the observed liver damage.", "contents": "An investigation into the hepatic cytochrome P-450 catalysed metabolism of the anaesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether). The role of the different cytochromes P-450 in the metabolism of the anaesthetic agent fluroxene, and the mechanism of production of toxic effects seen after pre-treatment of the animals with pehnobarbital prior to anaesthesia, have been investigated. Male rats were anaesthetized with fluroxene, or with 2,2,2-trifluroethyl ethyl ether, or with ethyl vinyl ether in an attempt to ascertain the in vivo toxic effects of the three anaesthetic agents. The resultant hepatic histology is reported. A study of the binding and metabolism of fluroxene by isolated rat hepatic microsomes was also made. We conclude that it is elevated levels of cytochrome P-450 which potentiate the toxicity of fluroxene anaesthesia in phenobarbital treated animals and that cytochrome P-448 does not bind or metabolize fluroxene. The potential toxicity of the fluroxene molecule is considered to reside in the trifluoroethyl moiety, while the vinyl group of fluroxene appears to play a role in the observed liver damage."}
{"id": "PMID:1865", "title": "Direct revascularization of acute myocardial infarction by implantation of left internal mammary artery into infarcted left ventricular myocardium.", "content": "This is a preliminary report. Clearly, the internal mammary artery implanted into the infarcted anterolateral portion of the wall of the left ventricle has been of help in decreasing the size of the infarction and in maintaining the life of the dogs and normal function six hours after a large left ventricular wall myocardial infarction had been created. More animals need to be studied at the end of six hours, eight hours, and ten hours after implantation. More studies are needed to learn if ligation of the coronary veins at the same time as the arteries is beneficial or not. Two internal mammary arteries may act better than one when implanted side by side into a 5 by 5 centimeter infarction. In man, both internal mammary arteries and the right gastroepiploic artery could be used to revascularize acute myocardial infarctions in the posterior and anterolateral parts of the left ventricle.", "contents": "Direct revascularization of acute myocardial infarction by implantation of left internal mammary artery into infarcted left ventricular myocardium. This is a preliminary report. Clearly, the internal mammary artery implanted into the infarcted anterolateral portion of the wall of the left ventricle has been of help in decreasing the size of the infarction and in maintaining the life of the dogs and normal function six hours after a large left ventricular wall myocardial infarction had been created. More animals need to be studied at the end of six hours, eight hours, and ten hours after implantation. More studies are needed to learn if ligation of the coronary veins at the same time as the arteries is beneficial or not. Two internal mammary arteries may act better than one when implanted side by side into a 5 by 5 centimeter infarction. In man, both internal mammary arteries and the right gastroepiploic artery could be used to revascularize acute myocardial infarctions in the posterior and anterolateral parts of the left ventricle."}
{"id": "PMID:1866", "title": "Chronic anemia, wound healing, and red cell 2,3-diphosphoglycerate.", "content": "Relationships between various types of chronic anemia, wound healing, and red cell 2,3-diphosphoglycerate (2,3 DPG) were examined in rabbits. Wound tensile strength and energy absorption were not affected by chronic iron-deficiency anemia, the chronic hemolytic anemia caused by intravenous water infusion nor by chronic hemolytic anemia caused by intravenous water infusion nor by chronic phenylhydrazine-induced anemia. Red cell 2,3 DPG levels were increased in the anemia of iron deficiency and were normal in the rabbits with chronic phenylhydrazine-induced anemia at the time of wound excision but were low following phynylhydrazine injection. The results show that chronic anemia per se does not affect the tensile strength and energy adsorption of wound healing. The findings suggest that the wound healing process may differ in certain types of anemia.", "contents": "Chronic anemia, wound healing, and red cell 2,3-diphosphoglycerate. Relationships between various types of chronic anemia, wound healing, and red cell 2,3-diphosphoglycerate (2,3 DPG) were examined in rabbits. Wound tensile strength and energy absorption were not affected by chronic iron-deficiency anemia, the chronic hemolytic anemia caused by intravenous water infusion nor by chronic hemolytic anemia caused by intravenous water infusion nor by chronic phenylhydrazine-induced anemia. Red cell 2,3 DPG levels were increased in the anemia of iron deficiency and were normal in the rabbits with chronic phenylhydrazine-induced anemia at the time of wound excision but were low following phynylhydrazine injection. The results show that chronic anemia per se does not affect the tensile strength and energy adsorption of wound healing. The findings suggest that the wound healing process may differ in certain types of anemia."}
{"id": "PMID:1868", "title": "Effects of beta-adrenergic stimulating and blocking agents on the adrenaline response and adenyl cyclase activity of leukocyte in monkey and human being.", "content": "Using the method in which leukocyte suspensions were incubated with NaF or metaproterenol at 30 degrees C for 15-30 min to allow them to convert 3H-ATP (10 muCi) to 3H-cyclic AMP, followed by separation of the formed 3H-cyclic AMP by common chromatography, the leukocyte adenyl cyclase activity of monkeys and human beings was measured with high reproducibility. The oral administration of metaproterenol increased the leukocyte adenyl cyclase activity which was stimulated by NaF and decreased the count of peripheral eosinophils in some of the monkeys. In the beta-adrenergic blockade of the monkey which was made by administration of propranolol, the leukocyte adenyl cyclase activity significantly decreased. The leukocyte adenyl cyclase from patients with coronary heart disease also decreased after oral medication with propranolol.", "contents": "Effects of beta-adrenergic stimulating and blocking agents on the adrenaline response and adenyl cyclase activity of leukocyte in monkey and human being. Using the method in which leukocyte suspensions were incubated with NaF or metaproterenol at 30 degrees C for 15-30 min to allow them to convert 3H-ATP (10 muCi) to 3H-cyclic AMP, followed by separation of the formed 3H-cyclic AMP by common chromatography, the leukocyte adenyl cyclase activity of monkeys and human beings was measured with high reproducibility. The oral administration of metaproterenol increased the leukocyte adenyl cyclase activity which was stimulated by NaF and decreased the count of peripheral eosinophils in some of the monkeys. In the beta-adrenergic blockade of the monkey which was made by administration of propranolol, the leukocyte adenyl cyclase activity significantly decreased. The leukocyte adenyl cyclase from patients with coronary heart disease also decreased after oral medication with propranolol."}
{"id": "PMID:1869", "title": "Human erythrocyte carbonic anhydrase B and C in chronic obstructive lung disease.", "content": "The levels of carbonic anhydrase B and C isozymes in human red cells were determined using a quantitative immunological technique in patients with chronic obstructive lung disease. A significant increase in the level of carbonic anhydrase B was observed in these patients, while the level of carbonic anhydrase C did not change substantially. Positive correlations were found between the level of carbonic anhydrase B and arterial CO2 tension and plasma HCO3 concentration. A negative correlation was observed between the levels of carbonic anhydrase B and blood pH. These findings suggest that the synthesis or degradation of carbonic anhydrase B isozyme is affected by arterial CO2 tension or plasma HC03 concentration. The clinical significance was also discussed in relation to these isozyme levels in red cell.", "contents": "Human erythrocyte carbonic anhydrase B and C in chronic obstructive lung disease. The levels of carbonic anhydrase B and C isozymes in human red cells were determined using a quantitative immunological technique in patients with chronic obstructive lung disease. A significant increase in the level of carbonic anhydrase B was observed in these patients, while the level of carbonic anhydrase C did not change substantially. Positive correlations were found between the level of carbonic anhydrase B and arterial CO2 tension and plasma HCO3 concentration. A negative correlation was observed between the levels of carbonic anhydrase B and blood pH. These findings suggest that the synthesis or degradation of carbonic anhydrase B isozyme is affected by arterial CO2 tension or plasma HC03 concentration. The clinical significance was also discussed in relation to these isozyme levels in red cell."}
{"id": "PMID:1873", "title": "Hemodynamic effects of aerosol propellants. II. Pulmonary circulation in the dog.", "content": "The inhalation of trichlorofluoromethane (FC11), dichlorotetrafluoroethane (FC114) and dichlorodifluoromethane (FC12) caused a reduction in mean aortic blood pressure but only FC11 and FC114 caused a reduction in mean pulmonary arterial pressure. The primary cause of the fall is a decrease in pulmonary blood flow. When blood flow to a lobe is kept constant and the adrenergic alpha receptors are blocked by injection of phentolamine, the inhalation of FC11 caused vasodilation. In the intact circulation, the vasodilation is masked by release of catecholamines which constrict the pulmonary blood vessels.", "contents": "Hemodynamic effects of aerosol propellants. II. Pulmonary circulation in the dog. The inhalation of trichlorofluoromethane (FC11), dichlorotetrafluoroethane (FC114) and dichlorodifluoromethane (FC12) caused a reduction in mean aortic blood pressure but only FC11 and FC114 caused a reduction in mean pulmonary arterial pressure. The primary cause of the fall is a decrease in pulmonary blood flow. When blood flow to a lobe is kept constant and the adrenergic alpha receptors are blocked by injection of phentolamine, the inhalation of FC11 caused vasodilation. In the intact circulation, the vasodilation is masked by release of catecholamines which constrict the pulmonary blood vessels."}
{"id": "PMID:1879", "title": "Human placental delta5-3beta hydroxysteroid dehydrogenase activity (delta5-3beta HSDH): intracellular distribution, kinetic properties, retroinhibition and influence of membrane delipidation.", "content": "Delta5-3beta HSDH activity has been assayed either by spectrophotometric method or by use of radioactive substrates. The enzymatic activity is equally distributed between mitochondrial and microsomal fractions verified by electronic microscopy. The specific activity is comparable in both fractions, as well as the optimal pH and the Km for NAD and for the substrates. The delta5-3beta Hut optimal pH, specific activity and sensitivity to the inhibitory action of various steroids are different when C19 and C21 steroids are used as substrates. Estrogens and cyclic AMP have also an inhibitory action on the oxidation of C21 steroids. Treatment of microsomal or mitochondrial membranes with phospholipase A releases fatty acids (mainly arachidonic) and decreases the enzymatic activity. \"Adsorbtion\" of the fatty acids on bovine serum albumin partially reactivates the delta5-3beta HSDH.", "contents": "Human placental delta5-3beta hydroxysteroid dehydrogenase activity (delta5-3beta HSDH): intracellular distribution, kinetic properties, retroinhibition and influence of membrane delipidation. Delta5-3beta HSDH activity has been assayed either by spectrophotometric method or by use of radioactive substrates. The enzymatic activity is equally distributed between mitochondrial and microsomal fractions verified by electronic microscopy. The specific activity is comparable in both fractions, as well as the optimal pH and the Km for NAD and for the substrates. The delta5-3beta Hut optimal pH, specific activity and sensitivity to the inhibitory action of various steroids are different when C19 and C21 steroids are used as substrates. Estrogens and cyclic AMP have also an inhibitory action on the oxidation of C21 steroids. Treatment of microsomal or mitochondrial membranes with phospholipase A releases fatty acids (mainly arachidonic) and decreases the enzymatic activity. \"Adsorbtion\" of the fatty acids on bovine serum albumin partially reactivates the delta5-3beta HSDH."}
{"id": "PMID:1884", "title": "[Hydrolysis of insoluble collagen of bull bones by Streptomyces griseus crystalline protease].", "content": "Hydrolysis of collagen was studied in the bull bone tissues by the Str. griseus crystalline protease. The amount of collagen hydrolyzed by it composed 6.6% and 16% after 4-hour and 6-hour hydrolysis, respectively. When the enzyme:substrate ratio is 1:50 hydrolysis proceeds most intensively; with a decrease in the ratio up to 1:1000 the average amount of peptides increase from 2.6 up to 4 amino acidic residua, respectively. Under conditions of denaturated collagen hydrolysis the content of hydroxyproline in solution as compared with the native one increases; in this case the links with the presence of imino-acids are easier to split, the more resistant being those formed by hydroxyproline. Within the limit of 20-45 degrees C hydrolysis of protein intensifies with a temperature rise. Within the pH range of 5.0-11.0 the maximal amount of alpha- NH2-groups and hydroxyproline is observed at pH 8.5, the minimal--at PH 5.0. Hydroxyproline in the composition of peptides appears at the beginning of hydrolysis whereas the free one of enzymes of the longer effect 24 h after the beginning of the experiment composes 12.2% of its total content in the solved products. In the insoluble part of the substrate after 3-hour hydrolysis tyrosine composes less than 25% of its initial amount in protein whereas phenyl alanine--over 70%. After 6-hour hydrolysis the solved part of the system contains about 30% of alanine and 8.9 and 6% of glycine, proline and hydroxyproline, respectively.", "contents": "[Hydrolysis of insoluble collagen of bull bones by Streptomyces griseus crystalline protease]. Hydrolysis of collagen was studied in the bull bone tissues by the Str. griseus crystalline protease. The amount of collagen hydrolyzed by it composed 6.6% and 16% after 4-hour and 6-hour hydrolysis, respectively. When the enzyme:substrate ratio is 1:50 hydrolysis proceeds most intensively; with a decrease in the ratio up to 1:1000 the average amount of peptides increase from 2.6 up to 4 amino acidic residua, respectively. Under conditions of denaturated collagen hydrolysis the content of hydroxyproline in solution as compared with the native one increases; in this case the links with the presence of imino-acids are easier to split, the more resistant being those formed by hydroxyproline. Within the limit of 20-45 degrees C hydrolysis of protein intensifies with a temperature rise. Within the pH range of 5.0-11.0 the maximal amount of alpha- NH2-groups and hydroxyproline is observed at pH 8.5, the minimal--at PH 5.0. Hydroxyproline in the composition of peptides appears at the beginning of hydrolysis whereas the free one of enzymes of the longer effect 24 h after the beginning of the experiment composes 12.2% of its total content in the solved products. In the insoluble part of the substrate after 3-hour hydrolysis tyrosine composes less than 25% of its initial amount in protein whereas phenyl alanine--over 70%. After 6-hour hydrolysis the solved part of the system contains about 30% of alanine and 8.9 and 6% of glycine, proline and hydroxyproline, respectively."}
{"id": "PMID:1888", "title": "Effect of heparin or saline dilution of blood on PCO2 and pH.", "content": "The effect of different dilutions with heparin solutions or saline on blood PCO2, pH and standard bicarbonate was investigated. Blood was first equilibrated to give about 40 or 60 mmHg PCO2. The solutions were in equilibrium with room air. The effect on blood PCO2 etc. could be fully explained by the dilution with a medium having a much lower PCO2. Thus, correction of the heparin solution to pH 7.40 and PCO2 40 mmHg eliminated the effect on PCO2, pH and standard bicarbonate. With ordinary procedure for blood heparinization (about 2% dilution) the effect is practically negligible.", "contents": "Effect of heparin or saline dilution of blood on PCO2 and pH. The effect of different dilutions with heparin solutions or saline on blood PCO2, pH and standard bicarbonate was investigated. Blood was first equilibrated to give about 40 or 60 mmHg PCO2. The solutions were in equilibrium with room air. The effect on blood PCO2 etc. could be fully explained by the dilution with a medium having a much lower PCO2. Thus, correction of the heparin solution to pH 7.40 and PCO2 40 mmHg eliminated the effect on PCO2, pH and standard bicarbonate. With ordinary procedure for blood heparinization (about 2% dilution) the effect is practically negligible."}
{"id": "PMID:1885", "title": "[Specific p-nitrophenyl phosphatase of yeast Pichia guilliermondii].", "content": "The cells of yeast P. guilliermondii contain specific p-nitrophenyl phosphatase (pNPPase), the level of which depends on the cells supply with inorganic phosphorus. Partially purified enzyme is activated by ions Mg2+, Co2+ and somewhat weaker -- by ions Fe2+. With the presence of Mg2+ the enzyme activity is inhibited by ions Cd2+, Zn2+, f-, Be2+, Cu2+, Mn2+, Ca2+, MoO42-, Fe3+, Fe2+, inorganic phosphate as well as by EDTA. A mixture ions Be2+ and F- causes a complete inhibition of the activity. Ions K+ and Na+ inhibit to some extent the enzymic activity, ATP removes the inhibitory effect of monovalent cations. Km of pNPPase is equal to 3.3-10(-4) M, the molecular weight determined by the method of gelfiltration is 60 000. The enzyme is the most active at 50 degrees C and pH 9,5 PNPPase does not manifest the phosphotranspherase activity in tris-HC1-buffer.", "contents": "[Specific p-nitrophenyl phosphatase of yeast Pichia guilliermondii]. The cells of yeast P. guilliermondii contain specific p-nitrophenyl phosphatase (pNPPase), the level of which depends on the cells supply with inorganic phosphorus. Partially purified enzyme is activated by ions Mg2+, Co2+ and somewhat weaker -- by ions Fe2+. With the presence of Mg2+ the enzyme activity is inhibited by ions Cd2+, Zn2+, f-, Be2+, Cu2+, Mn2+, Ca2+, MoO42-, Fe3+, Fe2+, inorganic phosphate as well as by EDTA. A mixture ions Be2+ and F- causes a complete inhibition of the activity. Ions K+ and Na+ inhibit to some extent the enzymic activity, ATP removes the inhibitory effect of monovalent cations. Km of pNPPase is equal to 3.3-10(-4) M, the molecular weight determined by the method of gelfiltration is 60 000. The enzyme is the most active at 50 degrees C and pH 9,5 PNPPase does not manifest the phosphotranspherase activity in tris-HC1-buffer."}
{"id": "PMID:1890", "title": "Diagnosis of renal tumor by gamma-glutamyltranspeptidase (EC 2.3.2.2).", "content": "A urinary enzyme pattern and kidney tissue pattern were investigated simultaneously in 117 urologic patients. In contrast to all other renal disorders only the sixteen malignant tumors of the kidney showed a significant drop of gamma-GT in tumor tissue and urine. So far urinary enzymology has been used only as screening test. Measurement of gamma-GT in urine, however, permits the diagnosis of kidney tumors.", "contents": "Diagnosis of renal tumor by gamma-glutamyltranspeptidase (EC 2.3.2.2). A urinary enzyme pattern and kidney tissue pattern were investigated simultaneously in 117 urologic patients. In contrast to all other renal disorders only the sixteen malignant tumors of the kidney showed a significant drop of gamma-GT in tumor tissue and urine. So far urinary enzymology has been used only as screening test. Measurement of gamma-GT in urine, however, permits the diagnosis of kidney tumors."}
{"id": "PMID:1891", "title": "Bilateral testicular seminoma in intra-abdominal testes.", "content": "A seminoma of both intra-abdominal testes in a forty-five-year-old patient is reported. Discovery of the tumor was fortuitous during admission for upper lobe pneumonia. Of particular interest in this case is that seminoma was found in both undescended testes. Surgical extirpation of both degenerated testes along with prostatic utricle was performed. The patient refused radiotherapy.", "contents": "Bilateral testicular seminoma in intra-abdominal testes. A seminoma of both intra-abdominal testes in a forty-five-year-old patient is reported. Discovery of the tumor was fortuitous during admission for upper lobe pneumonia. Of particular interest in this case is that seminoma was found in both undescended testes. Surgical extirpation of both degenerated testes along with prostatic utricle was performed. The patient refused radiotherapy."}
{"id": "PMID:1894", "title": "[Study of the amniotic fluid of sheep in the normal course of pregnancy and in abortion].", "content": "Cytologic, biochemical and immunoelectrophoretic studies were carried out of amniotic fluids in 100 ewes with normal pregnancy and 40 ewes that had miscarried. Each month of pregnancy a total of 20 and 8 animals of the two groups, respectively were studied. It was found that the biochemical and metabolic processes taking place in the fetus lead to changes in the amniotic fluids altering the pH value, the alkali reserve, the content of potassium, calcium, phosphorus, alkaline phosphatase as well as their bactericidal activity. More characteristic changes linked with pregnancy were observed in the cell composition of the amniotic fluids. With advancing in age the increase in cell count was accompanied (staining with Nile blue sulfate) with a rise of the \"orange cell\" content. The amniotic fluids of ewes with normal pregnancy were found to contain proteins which precipitated with hyper immune sera against blood serum and kidney, heart, and placenta proteins. In ewes that had miscarried the pH values of the amniotic fluids dropped in the months when abortions took place: 7.36, 7.11, 6.90, 6.80 and 6.90, as against 7.41, 7.36, 7.28, 7.17 and 7.18, respectively. Along with pH the alkali reserve also dropped to 37.9 in the first month and 14.20 in the fifth month. In ewes that had miscarried in the 2nd, 3rd, and 4th month these values were 18.90, 14.90, and 13.80 cu. cm, respectively. In cases of abortions the protein composition of the amniotic fluids showed higher levels of the alfa and beta globulins.", "contents": "[Study of the amniotic fluid of sheep in the normal course of pregnancy and in abortion]. Cytologic, biochemical and immunoelectrophoretic studies were carried out of amniotic fluids in 100 ewes with normal pregnancy and 40 ewes that had miscarried. Each month of pregnancy a total of 20 and 8 animals of the two groups, respectively were studied. It was found that the biochemical and metabolic processes taking place in the fetus lead to changes in the amniotic fluids altering the pH value, the alkali reserve, the content of potassium, calcium, phosphorus, alkaline phosphatase as well as their bactericidal activity. More characteristic changes linked with pregnancy were observed in the cell composition of the amniotic fluids. With advancing in age the increase in cell count was accompanied (staining with Nile blue sulfate) with a rise of the \"orange cell\" content. The amniotic fluids of ewes with normal pregnancy were found to contain proteins which precipitated with hyper immune sera against blood serum and kidney, heart, and placenta proteins. In ewes that had miscarried the pH values of the amniotic fluids dropped in the months when abortions took place: 7.36, 7.11, 6.90, 6.80 and 6.90, as against 7.41, 7.36, 7.28, 7.17 and 7.18, respectively. Along with pH the alkali reserve also dropped to 37.9 in the first month and 14.20 in the fifth month. In ewes that had miscarried in the 2nd, 3rd, and 4th month these values were 18.90, 14.90, and 13.80 cu. cm, respectively. In cases of abortions the protein composition of the amniotic fluids showed higher levels of the alfa and beta globulins."}
{"id": "PMID:1895", "title": "[Adrenal-like Leydig cells (author's transl)].", "content": "Adrenal-like lipoid-rich Leydig cells, which could be found in a cryptorchid testis, were investigated by light and electronmicroscopy. There were nodular and diffuse proliferation of these adrenal-like cells in the interstitium of the testis. Electronmicroscopically these cells are fasciculated and characterized by large liposomes, many tubulovesicular mitochondria, and a large smooth endoplasmatic reticulum. But the presence of crystals of Reinke in these cells underlined their relationship to Leydig cells. The clinical history of this case is characterised by an extreme adipositas (167 kg) and high urinary estrogenexcretion. This excretion could be suppressed with dexamethasone and stimulated with HCG. After orchiectomy estrogen excretion decreased for 4 months and then increased again, after ACTH stimulation performed by reason of adrenal insufficiency. At this time there is no evidence of adrenal tumor; in the contralateral, scrotal testis, spermiogenesis and Leydig cells are without pathologic changes as revealed by biopsy.", "contents": "[Adrenal-like Leydig cells (author's transl)]. Adrenal-like lipoid-rich Leydig cells, which could be found in a cryptorchid testis, were investigated by light and electronmicroscopy. There were nodular and diffuse proliferation of these adrenal-like cells in the interstitium of the testis. Electronmicroscopically these cells are fasciculated and characterized by large liposomes, many tubulovesicular mitochondria, and a large smooth endoplasmatic reticulum. But the presence of crystals of Reinke in these cells underlined their relationship to Leydig cells. The clinical history of this case is characterised by an extreme adipositas (167 kg) and high urinary estrogenexcretion. This excretion could be suppressed with dexamethasone and stimulated with HCG. After orchiectomy estrogen excretion decreased for 4 months and then increased again, after ACTH stimulation performed by reason of adrenal insufficiency. At this time there is no evidence of adrenal tumor; in the contralateral, scrotal testis, spermiogenesis and Leydig cells are without pathologic changes as revealed by biopsy."}
{"id": "PMID:1899", "title": "[Properties of partially purified ATP desaminase from Actinomyces N4 antibioticus].", "content": "Three active fractions of ATP desaminase from Actinomyces N4 of type Antibioticus were obtained by gel filtration through Sephadex G-200. Some properties of each fraction were studied: effect of pH and Mg2+, substrate specificity, effect of pH on Km. The enzyme studied could be used for preparation of ITP, IDP, IMP, inosine and hypoxantine.", "contents": "[Properties of partially purified ATP desaminase from Actinomyces N4 antibioticus]. Three active fractions of ATP desaminase from Actinomyces N4 of type Antibioticus were obtained by gel filtration through Sephadex G-200. Some properties of each fraction were studied: effect of pH and Mg2+, substrate specificity, effect of pH on Km. The enzyme studied could be used for preparation of ITP, IDP, IMP, inosine and hypoxantine."}
{"id": "PMID:1900", "title": "[Changes in the content of ribosomal RNA and the activity of ribosomal RNAase in the brain under natural physiological conditions].", "content": "Optimal activity of RNAase from brain ribosomal fraction was observed at pH 5.4 and pH 7.9. After alimentary and conditioned-alimentary stimulation content of rRNA was significantly increased in brain, but the RNAase activity was decreased more than two-fold. After conditioned-alimentary inhibition content of rRNA was slightly decreased as compared to experiments with alimentary and conditioned-alimentary stimulation, but it was distinctly higher than in control. As compared with alimentary stimulation in the conditioned-alimentary stimulation the RNAase activity was increased at pH 5.4 and decreased at pH 7.9.", "contents": "[Changes in the content of ribosomal RNA and the activity of ribosomal RNAase in the brain under natural physiological conditions]. Optimal activity of RNAase from brain ribosomal fraction was observed at pH 5.4 and pH 7.9. After alimentary and conditioned-alimentary stimulation content of rRNA was significantly increased in brain, but the RNAase activity was decreased more than two-fold. After conditioned-alimentary inhibition content of rRNA was slightly decreased as compared to experiments with alimentary and conditioned-alimentary stimulation, but it was distinctly higher than in control. As compared with alimentary stimulation in the conditioned-alimentary stimulation the RNAase activity was increased at pH 5.4 and decreased at pH 7.9."}
{"id": "PMID:1901", "title": "[Effect of the antibiotic D-cycloserine and its dimer on the activity of tyrosine aminotransferase in liver tissue of intact, adrenalectomized and hypophysectomized rats].", "content": "In a period of lowest day activity of tyrosine aminotransferase, within 6-8 days after bilatheral adrenalectomy, the enzyme activity was decreased by about 20% as compared with an adequate control. At the same time, within a day and seven days after hypophisectomy, in rat liver tissue the enzyme activity was increased, approximately two-fold as compared with the normal state. Within four hrs after intraperitoneal administration into intact fasting rats at a dose of 2-2.5 g per 1 kg of body weight D-cycloserine and its dimer caused an induction of tyrosine aminotransferase by 75% and 180%, respectively. Induction of the enzyme by D-cycloserine and its dimer was inhibited by actinomycin D; the phenomenon was not observed in adrenalectomized rats. Within a day after hypophisectomy D-cycloserine did not cause the induction of tyrosine aminotransferase in rat liver tissue; to the contrary, the dimer of D-cycloserine caused induction of the enzyme, comparable to the ACTH effect, in liver tissue of hypophisectomized rats.", "contents": "[Effect of the antibiotic D-cycloserine and its dimer on the activity of tyrosine aminotransferase in liver tissue of intact, adrenalectomized and hypophysectomized rats]. In a period of lowest day activity of tyrosine aminotransferase, within 6-8 days after bilatheral adrenalectomy, the enzyme activity was decreased by about 20% as compared with an adequate control. At the same time, within a day and seven days after hypophisectomy, in rat liver tissue the enzyme activity was increased, approximately two-fold as compared with the normal state. Within four hrs after intraperitoneal administration into intact fasting rats at a dose of 2-2.5 g per 1 kg of body weight D-cycloserine and its dimer caused an induction of tyrosine aminotransferase by 75% and 180%, respectively. Induction of the enzyme by D-cycloserine and its dimer was inhibited by actinomycin D; the phenomenon was not observed in adrenalectomized rats. Within a day after hypophisectomy D-cycloserine did not cause the induction of tyrosine aminotransferase in rat liver tissue; to the contrary, the dimer of D-cycloserine caused induction of the enzyme, comparable to the ACTH effect, in liver tissue of hypophisectomized rats."}
{"id": "PMID:1902", "title": "[Analysis of inhibition in pathways of NADP.H2 and NAD.H2 oxidation in liver tissue microsomes].", "content": "Microsomal complexes of electron transfer were resistant to typical inhibitors of mitochondrial pathway of electron transport. In oxidation of NADP.H2 there were at least three point of molecular O2 reduction: NADP.H2-specific flavoprotein, Fe2+ participating in reactions of peroxidation of unsaturated fatty acids and cytochrome P-450. Efficiency of cytochrome P-450 inhibitors could not be evaluated by polarography as in the pathway several sites of molecular O2 activation were observed. In oxidation of NADP.H2 estimation of the rate of electron transfer reactions was carried out by monitoring of velocity of O2 absorption in presence of EDTA (inhibitor of the reaction of peroxidation) because about 50% of the total oxygen were utilized only in the process where NADP.H2 was oxidized. NAD.H2 oxidation, inhibited with EDTA, was activated by addition of Ca2+.", "contents": "[Analysis of inhibition in pathways of NADP.H2 and NAD.H2 oxidation in liver tissue microsomes]. Microsomal complexes of electron transfer were resistant to typical inhibitors of mitochondrial pathway of electron transport. In oxidation of NADP.H2 there were at least three point of molecular O2 reduction: NADP.H2-specific flavoprotein, Fe2+ participating in reactions of peroxidation of unsaturated fatty acids and cytochrome P-450. Efficiency of cytochrome P-450 inhibitors could not be evaluated by polarography as in the pathway several sites of molecular O2 activation were observed. In oxidation of NADP.H2 estimation of the rate of electron transfer reactions was carried out by monitoring of velocity of O2 absorption in presence of EDTA (inhibitor of the reaction of peroxidation) because about 50% of the total oxygen were utilized only in the process where NADP.H2 was oxidized. NAD.H2 oxidation, inhibited with EDTA, was activated by addition of Ca2+."}
{"id": "PMID:1903", "title": "[The effect of hydrocortisone and insulin on the activity and isoenzyme of tyrosine-alpha-ketoglutarate transaminase in cytostructures of rat liver].", "content": "Single administration of hydrocortisone or insulin into rats (body weight 200 g) and also combined treatment of the animals with the hormones at large doses caused a distinct increase in activities of anode and cathode isoenzymes of tyrosine-alpha-ketoglutarate transaminase in soluble fraction; total activity of the enzyme was also increased in mitochondria of rat liver tissue.", "contents": "[The effect of hydrocortisone and insulin on the activity and isoenzyme of tyrosine-alpha-ketoglutarate transaminase in cytostructures of rat liver]. Single administration of hydrocortisone or insulin into rats (body weight 200 g) and also combined treatment of the animals with the hormones at large doses caused a distinct increase in activities of anode and cathode isoenzymes of tyrosine-alpha-ketoglutarate transaminase in soluble fraction; total activity of the enzyme was also increased in mitochondria of rat liver tissue."}
{"id": "PMID:1904", "title": "[Changes in cerebrospinal fluid lactate and pyruvate levels during brain surgery under fluotane anesthesia].", "content": "The lactate and pyruvate content in the arterial blood and CSF of 24 patients operated on the brain under fluothane anesthesia with artificial ventilation of the lungs was measured. Towards the end of the operation and anesthesia a sizably elevated lactate level and accumulation of its excess in the blood were noted, these shifts having been more marked with hypocapnic ventilation of the lungs. An increased concentration of lactate and pyruvate in the cerebrospinal fluid was not attended by accumulation of lactate excess.", "contents": "[Changes in cerebrospinal fluid lactate and pyruvate levels during brain surgery under fluotane anesthesia]. The lactate and pyruvate content in the arterial blood and CSF of 24 patients operated on the brain under fluothane anesthesia with artificial ventilation of the lungs was measured. Towards the end of the operation and anesthesia a sizably elevated lactate level and accumulation of its excess in the blood were noted, these shifts having been more marked with hypocapnic ventilation of the lungs. An increased concentration of lactate and pyruvate in the cerebrospinal fluid was not attended by accumulation of lactate excess."}
{"id": "PMID:1906", "title": "[Enterococcal survival in forcemeat preserved in polymer films and in cutlets made from it].", "content": "The available data suggest that at 2 degrees and 5 degrees with a 12-day long storage in unpacked and in polymeric film packed forcemeat there occurs no propagation of the enterococci. At 22-24 degrees the multiplication of Str. faecalis var. liquefaciens proceeded similarly both in packed and unpacked forcemeat. When the temperature in the central part of the cutlets prepared from the enterococci-contaminated forcemeat reaches 7-80 degrees the bulk of the Str. faecalis var liquefaciens cells perishes, but even at 80 degrees there survive individual heat-resistant cells.", "contents": "[Enterococcal survival in forcemeat preserved in polymer films and in cutlets made from it]. The available data suggest that at 2 degrees and 5 degrees with a 12-day long storage in unpacked and in polymeric film packed forcemeat there occurs no propagation of the enterococci. At 22-24 degrees the multiplication of Str. faecalis var. liquefaciens proceeded similarly both in packed and unpacked forcemeat. When the temperature in the central part of the cutlets prepared from the enterococci-contaminated forcemeat reaches 7-80 degrees the bulk of the Str. faecalis var liquefaciens cells perishes, but even at 80 degrees there survive individual heat-resistant cells."}
{"id": "PMID:1914", "title": "[Determination of GSH-DH activity (E.C.1.8.5.1) presence of the enzyme in different wheat varieties (author's transl)].", "content": "2,6-dichlorophenol-indophenol is more stable in 75% ethanol than in aqueous solution and ascorbic acid reacts considerably faster in this media than glutathione. The activity determination of glutathione: dehydroascorbic acid oxidoreductase was based on these observations by a photometric measurement of the ascorbic acid resulting from the catalysis. Extracts from various types of wheat were tested and relatively high enzyme activities were found.", "contents": "[Determination of GSH-DH activity (E.C.1.8.5.1) presence of the enzyme in different wheat varieties (author's transl)]. 2,6-dichlorophenol-indophenol is more stable in 75% ethanol than in aqueous solution and ascorbic acid reacts considerably faster in this media than glutathione. The activity determination of glutathione: dehydroascorbic acid oxidoreductase was based on these observations by a photometric measurement of the ascorbic acid resulting from the catalysis. Extracts from various types of wheat were tested and relatively high enzyme activities were found."}
{"id": "PMID:1907", "title": "[Comparative study of Aujeszky's disease virus reproduction in a suspension of poultry embryonic cells and tissues (author's transl)].", "content": "Reproduction of Aueski disease virus in suspension cultures of trysinized cells and mechanically minced tissue of chick, duck and quail embryos was compared. The optimal conditions for cultivation of vaccine and virulent strains of virus in these systems were determined. The advantages and prospects of using suspension cultures of minced avian embryo tissue for preparation of virus materials with high biological activity and in large volumes in comparison with trypsinized cell suspensions were demonstrated.", "contents": "[Comparative study of Aujeszky's disease virus reproduction in a suspension of poultry embryonic cells and tissues (author's transl)]. Reproduction of Aueski disease virus in suspension cultures of trysinized cells and mechanically minced tissue of chick, duck and quail embryos was compared. The optimal conditions for cultivation of vaccine and virulent strains of virus in these systems were determined. The advantages and prospects of using suspension cultures of minced avian embryo tissue for preparation of virus materials with high biological activity and in large volumes in comparison with trypsinized cell suspensions were demonstrated."}
{"id": "PMID:1913", "title": "[A pharmacologic analysis of preparatory mechanisms of stereotyped activity in dogs].", "content": "In dogs with elaborated rhythmic and mozaic stereotypes of secretory and motor situational conditioned reflexes specific features were revealed in the action of some neurotropic drugs (amizyl, amedine, diphacil, pediphene, chlorpromazine and sodium oxybutyrate) on preparatory (latent) conditions of excitation and inhibition, appearing in the stabilized systems of reflexes. Pharmacological analysis has pointed to the predominantly cholinergic nature of preparatory and trigger mechanisms of alimentary conditioned activity. The blockade of M-cholinoreceptors (by means of amizyl and amedine) weakens or eliminates the preparatory conditions appearing in a dynamic stereotype and disturbs the trigger reactions within three to ten days. A pediphene blockade of H-cholinoreceptors intensifies the preparatory states.", "contents": "[A pharmacologic analysis of preparatory mechanisms of stereotyped activity in dogs]. In dogs with elaborated rhythmic and mozaic stereotypes of secretory and motor situational conditioned reflexes specific features were revealed in the action of some neurotropic drugs (amizyl, amedine, diphacil, pediphene, chlorpromazine and sodium oxybutyrate) on preparatory (latent) conditions of excitation and inhibition, appearing in the stabilized systems of reflexes. Pharmacological analysis has pointed to the predominantly cholinergic nature of preparatory and trigger mechanisms of alimentary conditioned activity. The blockade of M-cholinoreceptors (by means of amizyl and amedine) weakens or eliminates the preparatory conditions appearing in a dynamic stereotype and disturbs the trigger reactions within three to ten days. A pediphene blockade of H-cholinoreceptors intensifies the preparatory states."}
{"id": "PMID:1915", "title": "[The distribution of benorylate in plasma, synovial fluid and synovial tissue in rheumatoid arthritis].", "content": "The authors report on the drug benorylate which is available in the Federal Republic under the name of Benortan (4-acetamidophenyl-2-acetoxybenzoat). Numerous examinations have shown that it is well tolerated by mouth and that it has beneficial clinical effects with few side effects. Benorylate is a neutral, fat-soluble, water-insoluble substance which upon absorption is almost completely hydrolyzed into salicylate and paracetamol. 6 patients with classical seropositive rheumatoid arthritis and with a highly active synovialitis of one or both knee joints not previously treated received 4 g of a 40% benorylate suspension orally twice daily over a period of 9-14 days. On different days at exactly determined times of drug administration blood, and on the day of synovectomy synovial fluid and synovial tissue, were taken and frozen to - 70 degrees C and subsequently examined as to the content of salicylate, paracetamol, and unchanged benorylate. The plasma levels of salicylate and paracetamol were generally distinctly higher than the concentrations of these metabolites in the synovial fluid. Benorylate which is practically not detectable in blood is found in the synovial tissue and is detectable in greatest quantities in the most inflamed synovial villi. Benorylate can probably penetrate into the synovial membrane like its metabolites salicylate and paracetamol; it remains, however, to be examined whether the metabolites are distributed differently in different synovial areas (active inflamed and unattacked synovial tissue, respectively) in the same way as benorylate per se.", "contents": "[The distribution of benorylate in plasma, synovial fluid and synovial tissue in rheumatoid arthritis]. The authors report on the drug benorylate which is available in the Federal Republic under the name of Benortan (4-acetamidophenyl-2-acetoxybenzoat). Numerous examinations have shown that it is well tolerated by mouth and that it has beneficial clinical effects with few side effects. Benorylate is a neutral, fat-soluble, water-insoluble substance which upon absorption is almost completely hydrolyzed into salicylate and paracetamol. 6 patients with classical seropositive rheumatoid arthritis and with a highly active synovialitis of one or both knee joints not previously treated received 4 g of a 40% benorylate suspension orally twice daily over a period of 9-14 days. On different days at exactly determined times of drug administration blood, and on the day of synovectomy synovial fluid and synovial tissue, were taken and frozen to - 70 degrees C and subsequently examined as to the content of salicylate, paracetamol, and unchanged benorylate. The plasma levels of salicylate and paracetamol were generally distinctly higher than the concentrations of these metabolites in the synovial fluid. Benorylate which is practically not detectable in blood is found in the synovial tissue and is detectable in greatest quantities in the most inflamed synovial villi. Benorylate can probably penetrate into the synovial membrane like its metabolites salicylate and paracetamol; it remains, however, to be examined whether the metabolites are distributed differently in different synovial areas (active inflamed and unattacked synovial tissue, respectively) in the same way as benorylate per se."}
{"id": "PMID:1947", "title": "[In vitro effect of leukocytic and thymic histones and their fractions on the activity of the causative agent of meningopneumonia].", "content": "It was found in studying the antimeningococcus activity of the leukocytic and thymus histones and their fractions that both histones were capable of neutralizing in vitro the activity of the causative agent of meningopneumonia (MP). The neutralization effect was chiefly associated with the F3 fraction rich in arginine and depended on the duration of the histone fraction contact with the MP causative agent, the weight concentration of the histone and the pH of the incubation medium.", "contents": "[In vitro effect of leukocytic and thymic histones and their fractions on the activity of the causative agent of meningopneumonia]. It was found in studying the antimeningococcus activity of the leukocytic and thymus histones and their fractions that both histones were capable of neutralizing in vitro the activity of the causative agent of meningopneumonia (MP). The neutralization effect was chiefly associated with the F3 fraction rich in arginine and depended on the duration of the histone fraction contact with the MP causative agent, the weight concentration of the histone and the pH of the incubation medium."}
{"id": "PMID:1948", "title": "[Immunological polyfunctionality of proteins and its meaning for the analysis of an allergen-active bacterial substrate].", "content": "It was shown with the aid of immunosorption of an allergen-active substrate of E. coli 020: K84 (No. 2-rII) that protein substances taking part in the phenomenon of cell hypersensitivity were active in the humoral immunity reactions. The allergenic and immunochemical activity served as functions of the same molecules of bacterial proteins, this substantiating the use of immunochemical analysis for the study of an allergen-active bacterial substrate. By protein denaturing it is possible to obtain immunochemical inert allergen-active preparations capable of detecting the cell hypersensitivity to crude bacterial proteins. The problem of immunological polyfunctionality of proteins is discussed from the aspect of nonhomogeneity of their antigenic determinant groups.", "contents": "[Immunological polyfunctionality of proteins and its meaning for the analysis of an allergen-active bacterial substrate]. It was shown with the aid of immunosorption of an allergen-active substrate of E. coli 020: K84 (No. 2-rII) that protein substances taking part in the phenomenon of cell hypersensitivity were active in the humoral immunity reactions. The allergenic and immunochemical activity served as functions of the same molecules of bacterial proteins, this substantiating the use of immunochemical analysis for the study of an allergen-active bacterial substrate. By protein denaturing it is possible to obtain immunochemical inert allergen-active preparations capable of detecting the cell hypersensitivity to crude bacterial proteins. The problem of immunological polyfunctionality of proteins is discussed from the aspect of nonhomogeneity of their antigenic determinant groups."}
{"id": "PMID:1949", "title": "[Some properties of the alpha-hemolysin produced by a hemolytic strain of E. coli].", "content": "It was found that alpha-hemolysin of E. coli P 678 HIy+ was maximally active against human erythrocytes at pH 6.5. The hemolytic activity is characterized in time by a distinct lag-phase and a phase of the greatest velocity of the reaction immediately following it. The duration of the lag-phase and also the rate of hemolysis depends on alpha-hemolysin concentration, whose increase is accompanied by a decrease of the lag-phase and acceleration of hemolysis. There is a definite limit below which the duration of the lag-phase remains unchanged with further increase of hemolysin concentration. There was noted a linear relationship between the amount of erythrocytes taken for the test and the rate of hemoglobin release and also a temperature activation of the hemolytic reaction.", "contents": "[Some properties of the alpha-hemolysin produced by a hemolytic strain of E. coli]. It was found that alpha-hemolysin of E. coli P 678 HIy+ was maximally active against human erythrocytes at pH 6.5. The hemolytic activity is characterized in time by a distinct lag-phase and a phase of the greatest velocity of the reaction immediately following it. The duration of the lag-phase and also the rate of hemolysis depends on alpha-hemolysin concentration, whose increase is accompanied by a decrease of the lag-phase and acceleration of hemolysis. There is a definite limit below which the duration of the lag-phase remains unchanged with further increase of hemolysin concentration. There was noted a linear relationship between the amount of erythrocytes taken for the test and the rate of hemoglobin release and also a temperature activation of the hemolytic reaction."}
{"id": "PMID:1950", "title": "[An experimental study of the spectrum of individual psychotropic activity of clozapine (Leponex)].", "content": "An experimental analysis of the psychotropic activity of Leponex (in a chronic experiment on II cats) in conditions of a group interaction depicted that the preparation processes a definite tranquillizing and antipsychotic effect. In conditions of zoosocial interactions this drug promotes disappearance of neurotic reactions and a resocialization of animals in the zoosocial ierarchy. In tranquillizing doses the preparation has an antihypertensive effect and prevents the development of a long-term tonic hypertension due to emotional stress.", "contents": "[An experimental study of the spectrum of individual psychotropic activity of clozapine (Leponex)]. An experimental analysis of the psychotropic activity of Leponex (in a chronic experiment on II cats) in conditions of a group interaction depicted that the preparation processes a definite tranquillizing and antipsychotic effect. In conditions of zoosocial interactions this drug promotes disappearance of neurotic reactions and a resocialization of animals in the zoosocial ierarchy. In tranquillizing doses the preparation has an antihypertensive effect and prevents the development of a long-term tonic hypertension due to emotional stress."}
{"id": "PMID:1951", "title": "Affinity elution of pyruvate kinase from phosphocellulose.", "content": "Pyruvate kinase from ascites tumour cells can be eluted from phosphocellulose by very low concentrations of phosphoenolpyruvate, fructose 1,6-bisphosphate, adenosine 5'-diphosphate and pyrophosphate, respectively. The appropriate limiting conditions for \"facilitated desorption\" of the enzyme from phosphocellulose by these ligands have been elaborated for achieving maximum selectivity and recovery in the process of its purification. This method has been designated as \"affinity elution chromatography\" owing to the specific interactions between a ligand as a constituent of the eluting medium with the adsorbed enzyme, which causes its selective desorption from the ion-exchanger. Affinity elution with phosphoenolpyruvate has been found to be very effective for preparation of the M-types of pyruvate kinase. A specific activity of 420 for an almost homogeneous preparation of pyruvate kinase from ascites tumour cells has maximally been obtained.", "contents": "Affinity elution of pyruvate kinase from phosphocellulose. Pyruvate kinase from ascites tumour cells can be eluted from phosphocellulose by very low concentrations of phosphoenolpyruvate, fructose 1,6-bisphosphate, adenosine 5'-diphosphate and pyrophosphate, respectively. The appropriate limiting conditions for \"facilitated desorption\" of the enzyme from phosphocellulose by these ligands have been elaborated for achieving maximum selectivity and recovery in the process of its purification. This method has been designated as \"affinity elution chromatography\" owing to the specific interactions between a ligand as a constituent of the eluting medium with the adsorbed enzyme, which causes its selective desorption from the ion-exchanger. Affinity elution with phosphoenolpyruvate has been found to be very effective for preparation of the M-types of pyruvate kinase. A specific activity of 420 for an almost homogeneous preparation of pyruvate kinase from ascites tumour cells has maximally been obtained."}
{"id": "PMID:1952", "title": "[Influence of temperature on enzyme activity determination in serum : L-aspartate aminotransferase isoenzymes].", "content": "The influence of temperature on activity assays of the isoenzymes of L-aspartic aminotransferase in described. For this purpose, isolated human isoenzymes were added to inactivated serum. Half-saturation constants were determined at 17.8 degrees C, 25 degrees C, 30 degrees C, and 37 degrees C, and the substrate saturation and pH curves were recorded. The cytoplasmatic (c) and mitochondrial (m) GOT showed temperature-dependent differences in the half-saturation constants for the substrates L-aspartate and 2-oxoglutarate. For both isoenzymes pH 7.4 is considered the optimum regardless of the temperature of measurement, and Tris-HCl is the optimal buffer. In the Arrhenius plot there is a bent at 27 degrees C for both isoenzymes. Thermal denaturation as a possible reason for this deviation from the linearity in the Arrhenius plot could be ruled out.", "contents": "[Influence of temperature on enzyme activity determination in serum : L-aspartate aminotransferase isoenzymes]. The influence of temperature on activity assays of the isoenzymes of L-aspartic aminotransferase in described. For this purpose, isolated human isoenzymes were added to inactivated serum. Half-saturation constants were determined at 17.8 degrees C, 25 degrees C, 30 degrees C, and 37 degrees C, and the substrate saturation and pH curves were recorded. The cytoplasmatic (c) and mitochondrial (m) GOT showed temperature-dependent differences in the half-saturation constants for the substrates L-aspartate and 2-oxoglutarate. For both isoenzymes pH 7.4 is considered the optimum regardless of the temperature of measurement, and Tris-HCl is the optimal buffer. In the Arrhenius plot there is a bent at 27 degrees C for both isoenzymes. Thermal denaturation as a possible reason for this deviation from the linearity in the Arrhenius plot could be ruled out."}
{"id": "PMID:1953", "title": "[Studies of in vitro cultivated cells from the smooth muscle organs. 3. Effectiveness of some drugs on pulsation frequency of isolated smooth muscle cells of the chicken amnion].", "content": "The effects of some drugs on the beating frequency of isolated cells of the chick amnion cultivated on cover slips were investigated. Cholinergic and adrenergic agonists and antagonists, serotonine, antispasmodics, coronary dilatants and local anesthetics influenced the beating frequency significantly. The isolated chick amnion cells equal in their pharmacological behaviour the intact chick amnion and smooth muscle cells of mammals but differ from isolated beating heart cells.", "contents": "[Studies of in vitro cultivated cells from the smooth muscle organs. 3. Effectiveness of some drugs on pulsation frequency of isolated smooth muscle cells of the chicken amnion]. The effects of some drugs on the beating frequency of isolated cells of the chick amnion cultivated on cover slips were investigated. Cholinergic and adrenergic agonists and antagonists, serotonine, antispasmodics, coronary dilatants and local anesthetics influenced the beating frequency significantly. The isolated chick amnion cells equal in their pharmacological behaviour the intact chick amnion and smooth muscle cells of mammals but differ from isolated beating heart cells."}
{"id": "PMID:1954", "title": "[Modification of the adjuvans arthritis by carrageenin, compound 48/80, histamine- and serotonin antagonists, non-steroid antiphlogistics as well as protease inhibitors and their possible relations to inflammation mediators].", "content": "1. Injections of carrageenin (1,25 mg/kg i.v.) from the 1st to the 3rd day and then each 2nd or 3rd day inhibited paw swelling in adjuvant arthritis of the rat during the time of treatment. Injections from the 11th to the 15th day were ineffective. The level of plasma kininogen was slightly decreased but the total complement serum level was significantly lowered. 2,5 and 3 mg carrageenin/kg respectively were toxic after repeated injections. After a single administration the levels of plasma kininogen and of total serum complement were decreased by 50% although paw swelling was not affected. 2. Pentosane polysulfoester (25 mg/kg i.v.) did not influence paw swelling despite daily administration from the 1st to the 17th day. Heparin (10 000 IE/kg i.v.) was likewise ineffective. 3. Single or repeated injections of compound 48/80 (0,125-0,5 mg/kg i.v.; 1-5 mg/kg i.p.; 3-6 mg/kg s.c.), reserpine (0,2 mg/kg i.p.), cyproheptadine (5 mg/kg i.v.), bromolysergic acid diethylamide (2 x 2 mg/kg i.v.) or metiamide (10 mg/kg i.v.) were without effect on paw swelling. Neither did compound 48/80 effect the complement serum level. 4. Daily administration of chloropromazine (4-10 mg/kg p.o.) or of promethazine (10-15 mg/kg s.c. or p.o.) inhibited paw swelling in the first phase of adjuvant arthritis but not in the second one. 5. The soybean trypsin inhibitor (15 mg/kg i.v.) inhibited paw swelling significantly up to the 4th day, the Kunitz inhibitor (25 000 E/kg i.v.) was ineffective. 6. The content of prostaglandin E of the inflamed paws was increased threefold in both phases of arthritis. The results are discussed with regard to the putative role of mediators of inflammation (histamine, serotonin, kinins, prostaglandins, lysosomal enzymes, lymphokines, complement).", "contents": "[Modification of the adjuvans arthritis by carrageenin, compound 48/80, histamine- and serotonin antagonists, non-steroid antiphlogistics as well as protease inhibitors and their possible relations to inflammation mediators]. 1. Injections of carrageenin (1,25 mg/kg i.v.) from the 1st to the 3rd day and then each 2nd or 3rd day inhibited paw swelling in adjuvant arthritis of the rat during the time of treatment. Injections from the 11th to the 15th day were ineffective. The level of plasma kininogen was slightly decreased but the total complement serum level was significantly lowered. 2,5 and 3 mg carrageenin/kg respectively were toxic after repeated injections. After a single administration the levels of plasma kininogen and of total serum complement were decreased by 50% although paw swelling was not affected. 2. Pentosane polysulfoester (25 mg/kg i.v.) did not influence paw swelling despite daily administration from the 1st to the 17th day. Heparin (10 000 IE/kg i.v.) was likewise ineffective. 3. Single or repeated injections of compound 48/80 (0,125-0,5 mg/kg i.v.; 1-5 mg/kg i.p.; 3-6 mg/kg s.c.), reserpine (0,2 mg/kg i.p.), cyproheptadine (5 mg/kg i.v.), bromolysergic acid diethylamide (2 x 2 mg/kg i.v.) or metiamide (10 mg/kg i.v.) were without effect on paw swelling. Neither did compound 48/80 effect the complement serum level. 4. Daily administration of chloropromazine (4-10 mg/kg p.o.) or of promethazine (10-15 mg/kg s.c. or p.o.) inhibited paw swelling in the first phase of adjuvant arthritis but not in the second one. 5. The soybean trypsin inhibitor (15 mg/kg i.v.) inhibited paw swelling significantly up to the 4th day, the Kunitz inhibitor (25 000 E/kg i.v.) was ineffective. 6. The content of prostaglandin E of the inflamed paws was increased threefold in both phases of arthritis. The results are discussed with regard to the putative role of mediators of inflammation (histamine, serotonin, kinins, prostaglandins, lysosomal enzymes, lymphokines, complement)."}
{"id": "PMID:1956", "title": "Properties of plasma membranes from granulation tissue with reference to extracellular matrix.", "content": "Treatment with neuraminidase decreased the activity of Na+,K+-activated Mg2+-adenosine triphosphatase in plasma membranes isolated from experimental granulation tissue but not that of 5'-nucleotidase or leucine-beta-naphthylamidase. A temporary lowering of the pH of the plasma membrane suspension to 2-3 inactivated all three enzymes, which remained inactive after the pH had been readjusted to 7.4. Addition of dextran preparations to the membrane suspension decreased the activity of adenosine triphosphatase. Ethanol (0.4%) had a similar effect. These marker enzymes of plasma membranes were not affected by additions of hyaluronate, chondroitin sulfate, protein polysaccharide or soluble collagen. Serotonin stimulated the adenosine triphosphatase activity slightly. About 10-20% of the protein in the plasma membrane preparation was extracted with EDTA. This \"fuzzy coat\" fraction yielded a distinct gel-electrophoretic protein pattern. Hyaluronidase was not helpful in cleaving this surface layer from the plasma membranes.", "contents": "Properties of plasma membranes from granulation tissue with reference to extracellular matrix. Treatment with neuraminidase decreased the activity of Na+,K+-activated Mg2+-adenosine triphosphatase in plasma membranes isolated from experimental granulation tissue but not that of 5'-nucleotidase or leucine-beta-naphthylamidase. A temporary lowering of the pH of the plasma membrane suspension to 2-3 inactivated all three enzymes, which remained inactive after the pH had been readjusted to 7.4. Addition of dextran preparations to the membrane suspension decreased the activity of adenosine triphosphatase. Ethanol (0.4%) had a similar effect. These marker enzymes of plasma membranes were not affected by additions of hyaluronate, chondroitin sulfate, protein polysaccharide or soluble collagen. Serotonin stimulated the adenosine triphosphatase activity slightly. About 10-20% of the protein in the plasma membrane preparation was extracted with EDTA. This \"fuzzy coat\" fraction yielded a distinct gel-electrophoretic protein pattern. Hyaluronidase was not helpful in cleaving this surface layer from the plasma membranes."}
{"id": "PMID:1957", "title": "Serum gastrin concentration before and after parietal cell vagotomy in man and dog.", "content": "Serum gastrin concentrations were measured during fasting and after feeding in duodenal ulcer patients and in dogs before and after parietal cell vagotomy (PCV). Postoperatively, fasting serum gastrin concentrations increased significantly in man and insignificantly higher in dog. After feeding, serum gastrin reached higher values postoperatively in both man and dog. The percentage rise in food-stimulated serum gastrin after PCV was higher in dog than in man.", "contents": "Serum gastrin concentration before and after parietal cell vagotomy in man and dog. Serum gastrin concentrations were measured during fasting and after feeding in duodenal ulcer patients and in dogs before and after parietal cell vagotomy (PCV). Postoperatively, fasting serum gastrin concentrations increased significantly in man and insignificantly higher in dog. After feeding, serum gastrin reached higher values postoperatively in both man and dog. The percentage rise in food-stimulated serum gastrin after PCV was higher in dog than in man."}
{"id": "PMID:1959", "title": "[Comparative study of a new antihistamine, mequitazine, and placebos].", "content": "In a double-blind trial lasting 2 weeks, a new, long-acting antihistamine, Mequitazine, and a placebo, were compared. 115 allergic patients participated in this experiment (mequitazine n = 56, placebo n = 59). Therapeutic results and the effect on diurnal alertness were evaluated by means of a questionnaire filled in daily by the patients. Whether considering the day by day results or the results of the entire treatment period, statistically, Mequitazine (10 mg/24 hrs) is very significantly more active than the placebo. The daytime drowsiness induced by Mequitazine is statistically no greater than that induced by the placebo, whether analyzed on a day by day basis or over the entire treatment period (P = 0.23). The side effects, 8 for Mequitazine, 5 for placebo, are mild and did not lead to discontinuation of the treatment in the Mequitazine group.", "contents": "[Comparative study of a new antihistamine, mequitazine, and placebos]. In a double-blind trial lasting 2 weeks, a new, long-acting antihistamine, Mequitazine, and a placebo, were compared. 115 allergic patients participated in this experiment (mequitazine n = 56, placebo n = 59). Therapeutic results and the effect on diurnal alertness were evaluated by means of a questionnaire filled in daily by the patients. Whether considering the day by day results or the results of the entire treatment period, statistically, Mequitazine (10 mg/24 hrs) is very significantly more active than the placebo. The daytime drowsiness induced by Mequitazine is statistically no greater than that induced by the placebo, whether analyzed on a day by day basis or over the entire treatment period (P = 0.23). The side effects, 8 for Mequitazine, 5 for placebo, are mild and did not lead to discontinuation of the treatment in the Mequitazine group."}
{"id": "PMID:1960", "title": "Beclomethasone dipropionate aerosol treatment of hay fever. A dose-response investigation.", "content": "In a controlled, double-blind study 20 children and adults, suffering from summer hay fever, were treated intranasally with a daily dose of 200 mug, 300 mug or 400 mug beclomethasone dipropionate (Beconase, Becotide Nasal) or with placebo for 2 weeks during the hay fever season. No beneficial effect of the placebo treatment was observed. In patients treated with 200 mug and 300 mug beclomethasone dipropionate a day there was a moderate decrease in nasal symptom scores and in use of antihistamine tablets. As the results indicated 400 mug a day to have the most pronounced effect on nasal symptoms, this dosage is recommended for children as well as adults suffering from summer hay fever.", "contents": "Beclomethasone dipropionate aerosol treatment of hay fever. A dose-response investigation. In a controlled, double-blind study 20 children and adults, suffering from summer hay fever, were treated intranasally with a daily dose of 200 mug, 300 mug or 400 mug beclomethasone dipropionate (Beconase, Becotide Nasal) or with placebo for 2 weeks during the hay fever season. No beneficial effect of the placebo treatment was observed. In patients treated with 200 mug and 300 mug beclomethasone dipropionate a day there was a moderate decrease in nasal symptom scores and in use of antihistamine tablets. As the results indicated 400 mug a day to have the most pronounced effect on nasal symptoms, this dosage is recommended for children as well as adults suffering from summer hay fever."}
{"id": "PMID:1961", "title": "Influence of changes in arterial PCO2 on cerebral blood flow and cerebral energy state during hypothermia in the rat.", "content": "In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artifically ventilated rats was decreased to 22 degreesC, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37 degrees C) over the PaCO2 range 15-60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22 degrees C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at PaCO2 values of 15, 30 and 60 mm Hg. The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when PaCO2 was increased from about 35 to about 60 mm Hg. However, with a decrease in PaCO2 the reduction in CBF was much more pronounced in hypothermia, and at PaCO2 15 Mm Hg CBF was less then 20% of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases.", "contents": "Influence of changes in arterial PCO2 on cerebral blood flow and cerebral energy state during hypothermia in the rat. In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artifically ventilated rats was decreased to 22 degreesC, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37 degrees C) over the PaCO2 range 15-60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22 degrees C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at PaCO2 values of 15, 30 and 60 mm Hg. The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when PaCO2 was increased from about 35 to about 60 mm Hg. However, with a decrease in PaCO2 the reduction in CBF was much more pronounced in hypothermia, and at PaCO2 15 Mm Hg CBF was less then 20% of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases."}
{"id": "PMID:1962", "title": "Neurohistological and histochemical observations on the lung of Rattus rattus rufescens (Indian black rat).", "content": "The intrinsic innervation of the lungs (right and left) has been studied by the cholinesterase technique, considering the effect of various pH, incubation periods and temperatures. Cholinergic innervation dominated. The peribronchial ganglia, large, medium-sized and irregular-shaped, rounded and small, showed a positive cholinesterase reaction. Maximum ChE activity was noticed in the bronchi and their branches and on the periphery of the alveoli.", "contents": "Neurohistological and histochemical observations on the lung of Rattus rattus rufescens (Indian black rat). The intrinsic innervation of the lungs (right and left) has been studied by the cholinesterase technique, considering the effect of various pH, incubation periods and temperatures. Cholinergic innervation dominated. The peribronchial ganglia, large, medium-sized and irregular-shaped, rounded and small, showed a positive cholinesterase reaction. Maximum ChE activity was noticed in the bronchi and their branches and on the periphery of the alveoli."}
{"id": "PMID:1963", "title": "Response of the hypothalamic neurosecretory system of the female catfish, Heteropneustes fossilis (Bloch), to hypophysectomy.", "content": "The effect of hypophysectomy on the hypothalamic neurosecretory system of the catfish, H. fossilis, was studied. Hypophysectomy resulted initially in an accumulation of NSM at the distal ends of the cut axons. The axons had grown and were reorganized into a neurohypophysis-like structure 3 weeks after hypophysectomy, and this persisted even more than 3 years post-hypophysectomy.", "contents": "Response of the hypothalamic neurosecretory system of the female catfish, Heteropneustes fossilis (Bloch), to hypophysectomy. The effect of hypophysectomy on the hypothalamic neurosecretory system of the catfish, H. fossilis, was studied. Hypophysectomy resulted initially in an accumulation of NSM at the distal ends of the cut axons. The axons had grown and were reorganized into a neurohypophysis-like structure 3 weeks after hypophysectomy, and this persisted even more than 3 years post-hypophysectomy."}
{"id": "PMID:1967", "title": "Reactions of the arterial blood pressure in changed haemodynamic conditions and under the effect of bilateral carotid occlusion.", "content": "In order to throw light on the problems related to the magnitude and the possibility of maintaining pressor response in the case of bilateral carotid occlusion (BCO), acute experiments were carried out on heparinized cats in chloralose-urethane narcosis and spontaneous respiration. The perfusion pressure in a hind leg autoperfused with a roller pump with a constant flow and the arterial blood pressure were recorded electromanometrically. A study was made of the changes taking place under the effect of BCO in the normal animal, in animals in a haemorrhagic state, after pharmacological alpha-adrenergic blockade, haemorrhage after alpha-adrenergic blockade, retransfusion of blood + alpha-adrenergic blocking agent and after local application of 0.01 papaverine. It was established that some of the factors determining the haemodynamic state of the organism, such as: blood volume, arterial pressure, vascular resistance, cardiac output, etc., are of great significance for the realization of the pressor response to BCO, but the haemodynamic state of the animal before the occlusion and the interactions between the abovementioned factors are decisive for the form, magnitude and maintenance of the pressor response in BCO.", "contents": "Reactions of the arterial blood pressure in changed haemodynamic conditions and under the effect of bilateral carotid occlusion. In order to throw light on the problems related to the magnitude and the possibility of maintaining pressor response in the case of bilateral carotid occlusion (BCO), acute experiments were carried out on heparinized cats in chloralose-urethane narcosis and spontaneous respiration. The perfusion pressure in a hind leg autoperfused with a roller pump with a constant flow and the arterial blood pressure were recorded electromanometrically. A study was made of the changes taking place under the effect of BCO in the normal animal, in animals in a haemorrhagic state, after pharmacological alpha-adrenergic blockade, haemorrhage after alpha-adrenergic blockade, retransfusion of blood + alpha-adrenergic blocking agent and after local application of 0.01 papaverine. It was established that some of the factors determining the haemodynamic state of the organism, such as: blood volume, arterial pressure, vascular resistance, cardiac output, etc., are of great significance for the realization of the pressor response to BCO, but the haemodynamic state of the animal before the occlusion and the interactions between the abovementioned factors are decisive for the form, magnitude and maintenance of the pressor response in BCO."}
{"id": "PMID:1968", "title": "On the mechanism of the relaxing adrenaline effect on cat jejunum.", "content": "The effect of propranolol, phentolamine, papaverine, theophyline and Ca++, administered in different combinations of their threshold doses, on the relaxing effect of adrenaline was studied on an isolated segment of proximal jejunum of male cats. It was established that phentolamine weakened the relaxing effect of adrenaline, while propranolol had no effect on it. Papaverine potentiated the relaxinf effects of adrenaline both when administered alone and in combination with propranolol or with phentolamine. Theophylline weakened the relaxing effect of adfrenaline and of the combination phentolamine-adrenaline. Ca++ increased the smooth-muscle tone. The interpretation of the results obtained leads to the fundamental conclusions that the relaxing effect of adrenaline on cat jejunum is more alpha- than beta-adrenergically determined and that the system of the cyclic AMP participates in its realization. At the smae time, however, the possibility of participation of other mechanisms is not excluded. The smooth-muscle effect of papaverine and theophylline is not determined only by their inhibitory effect on phosphodiesterase.", "contents": "On the mechanism of the relaxing adrenaline effect on cat jejunum. The effect of propranolol, phentolamine, papaverine, theophyline and Ca++, administered in different combinations of their threshold doses, on the relaxing effect of adrenaline was studied on an isolated segment of proximal jejunum of male cats. It was established that phentolamine weakened the relaxing effect of adrenaline, while propranolol had no effect on it. Papaverine potentiated the relaxinf effects of adrenaline both when administered alone and in combination with propranolol or with phentolamine. Theophylline weakened the relaxing effect of adfrenaline and of the combination phentolamine-adrenaline. Ca++ increased the smooth-muscle tone. The interpretation of the results obtained leads to the fundamental conclusions that the relaxing effect of adrenaline on cat jejunum is more alpha- than beta-adrenergically determined and that the system of the cyclic AMP participates in its realization. At the smae time, however, the possibility of participation of other mechanisms is not excluded. The smooth-muscle effect of papaverine and theophylline is not determined only by their inhibitory effect on phosphodiesterase."}
{"id": "PMID:1970", "title": "A method for the continuous study of net water transport in the feline small bowel.", "content": "A new perfusion technique has been developed for the study of net water transport across the intestinal epithelium in vivo. The lumen of an isolated intestinal segment is steadily perfused with a solution of known composition in a closed perfusion system with a reservoir large enough to prevent recirculation. The intestinal segment may be enclosed in a plethysmorgraph. Changes in the perfused volume is recorded by a volume transducer coupled to the recirculating system via a T-tube. If no motility occurs, the changes of the perfusion volume reflects net water transport across the intestinal epithelium. A quantitative comparison of this technique with the convention polyethylene glycol method revealed no significant difference. The plethysmorgraphic method also makes it possible to quantify the net water absorption via lymph and blood.", "contents": "A method for the continuous study of net water transport in the feline small bowel. A new perfusion technique has been developed for the study of net water transport across the intestinal epithelium in vivo. The lumen of an isolated intestinal segment is steadily perfused with a solution of known composition in a closed perfusion system with a reservoir large enough to prevent recirculation. The intestinal segment may be enclosed in a plethysmorgraph. Changes in the perfused volume is recorded by a volume transducer coupled to the recirculating system via a T-tube. If no motility occurs, the changes of the perfusion volume reflects net water transport across the intestinal epithelium. A quantitative comparison of this technique with the convention polyethylene glycol method revealed no significant difference. The plethysmorgraphic method also makes it possible to quantify the net water absorption via lymph and blood."}
{"id": "PMID:1971", "title": "Effect of bulbar acidification on basal secretion of acid and gastrin in dog.", "content": "Dogs were provided with mucosal septal pouches of the stomach and of the duodenal bulb. In some dogs a drainage gastric cannula was inserted into the most dependent portion of the stomach. In dogs which were found to secrete acid spontaneously during a control period at the start of each experiment, the bulbar puches were perfused with 0.1 M HC1 for 5-120 min. Bulbar acidification rapidly and profoundly reduced the basal acid output. In dogs which did not secrete acid spontaneously during the control periodbulbar pouches were perfused with 0.1 M HC1 for 1 h. Bulbar acidification did not significantly influence the plasma gastrin concentration and no acid was secreted from the Pavlov pouches following such acidification. The present results support the hypothesis that reduction of the intrabulbar pH may contribute to the reduction of acid secretion during interdigestive periods. The physiological significance of of mechanisms in the upper intestine which induce acid secretion following a reduction of the intraluminal pH is questioned.", "contents": "Effect of bulbar acidification on basal secretion of acid and gastrin in dog. Dogs were provided with mucosal septal pouches of the stomach and of the duodenal bulb. In some dogs a drainage gastric cannula was inserted into the most dependent portion of the stomach. In dogs which were found to secrete acid spontaneously during a control period at the start of each experiment, the bulbar puches were perfused with 0.1 M HC1 for 5-120 min. Bulbar acidification rapidly and profoundly reduced the basal acid output. In dogs which did not secrete acid spontaneously during the control periodbulbar pouches were perfused with 0.1 M HC1 for 1 h. Bulbar acidification did not significantly influence the plasma gastrin concentration and no acid was secreted from the Pavlov pouches following such acidification. The present results support the hypothesis that reduction of the intrabulbar pH may contribute to the reduction of acid secretion during interdigestive periods. The physiological significance of of mechanisms in the upper intestine which induce acid secretion following a reduction of the intraluminal pH is questioned."}
{"id": "PMID:1982", "title": "Differentiation of newly isolated strains of Trypanosoma (Schizotrypanum) cruzi by agglutination and precipitation reactions.", "content": "Serological relationships between new isolates of Trypanosoma cruzi from a single locality have been examined by direct agglutination and immunodiffusion, and compared with established strains. The strains were divided into three groups according to the absorption properties of their precipitinogens. The three groups were defined by the same characteristics as those in which strains of wide-ranging provenance and long laboratory history have been placed by previous workers. A lack of correspondence between the antigenic constitutions of the groups as described here and as described previously was demonstrated using reference strains. Relatedness values were calculated from agglutination titres, which indicated a complex heterogeneity of antigens, and from which a scheme of relationships was drawn.", "contents": "Differentiation of newly isolated strains of Trypanosoma (Schizotrypanum) cruzi by agglutination and precipitation reactions. Serological relationships between new isolates of Trypanosoma cruzi from a single locality have been examined by direct agglutination and immunodiffusion, and compared with established strains. The strains were divided into three groups according to the absorption properties of their precipitinogens. The three groups were defined by the same characteristics as those in which strains of wide-ranging provenance and long laboratory history have been placed by previous workers. A lack of correspondence between the antigenic constitutions of the groups as described here and as described previously was demonstrated using reference strains. Relatedness values were calculated from agglutination titres, which indicated a complex heterogeneity of antigens, and from which a scheme of relationships was drawn."}
{"id": "PMID:1979", "title": "Classification and biological distribution of histamine receptor sub-types.", "content": "The distribution and classification of histamine receptors in mammalian and avian tissues have been summarized in Tables 1-4. It is evident that histamine receptors are present on a number of morphologically distinct cell types and the proportion of cells bearing H1- and H2-receptors varies not only with the species but also with the cell source. The pharmacological receptors mediating mepyramine-sensitive histamine responses have been defined as H1-receptors. Receptors mediating mepyramine-resistant, but burimamide or metiamide-sensitive histamine responses have been classified as H2-receptors. Histamine responses mediated via H2-receptors seem to involve the adenylcyclase system resulting in elevation of intracellular cyclic-AMP level, which is susceptible to burimamide blockade but insensitive to beta-adrenergic blocking agents. This mode of action of histamine involving H2-receptors and the adenyl cyclase system has been shown to stimulate the mammalian heart; promote gastric acid secretion; inhibit antigen-induced histamine release from leucocytes and inhibit lymphocyte-mediated cytotoxicity. It can further be concluded that both H1- and H2-receptors are widely distributed throughout the animal body in the gastro-intestinal, reproductive, respiratory and cardiovascular systems, nervous system and on mast cells and blood leucocytes. In these tissues, histamine receptors play an important role in physiological, immunological and immunopathological processes. Interaction of histamine with both H1- and H2-receptors in varying proportions modulates the overall manifestation of cardiovascular and respiratory syndromes during certain immunopathological conditions (e.g. inflammation, allergy and anaphylaxis). Histamine receptors also appear to play and important role in the development of immuno-competence and immunity.", "contents": "Classification and biological distribution of histamine receptor sub-types. The distribution and classification of histamine receptors in mammalian and avian tissues have been summarized in Tables 1-4. It is evident that histamine receptors are present on a number of morphologically distinct cell types and the proportion of cells bearing H1- and H2-receptors varies not only with the species but also with the cell source. The pharmacological receptors mediating mepyramine-sensitive histamine responses have been defined as H1-receptors. Receptors mediating mepyramine-resistant, but burimamide or metiamide-sensitive histamine responses have been classified as H2-receptors. Histamine responses mediated via H2-receptors seem to involve the adenylcyclase system resulting in elevation of intracellular cyclic-AMP level, which is susceptible to burimamide blockade but insensitive to beta-adrenergic blocking agents. This mode of action of histamine involving H2-receptors and the adenyl cyclase system has been shown to stimulate the mammalian heart; promote gastric acid secretion; inhibit antigen-induced histamine release from leucocytes and inhibit lymphocyte-mediated cytotoxicity. It can further be concluded that both H1- and H2-receptors are widely distributed throughout the animal body in the gastro-intestinal, reproductive, respiratory and cardiovascular systems, nervous system and on mast cells and blood leucocytes. In these tissues, histamine receptors play an important role in physiological, immunological and immunopathological processes. Interaction of histamine with both H1- and H2-receptors in varying proportions modulates the overall manifestation of cardiovascular and respiratory syndromes during certain immunopathological conditions (e.g. inflammation, allergy and anaphylaxis). Histamine receptors also appear to play and important role in the development of immuno-competence and immunity."}
{"id": "PMID:1983", "title": "Identification of T. brucei-subgroup strains isolated from game.", "content": "Several T. brucei-subgroup strains isolated from game were investigated with the blood incubation infectivity test (BIIT) and in human volunteers. Original isolates and their clones derivatives were tested. In order to check the validity of the BIIT, volunteer tested clones were used under modified BIIT conditions. Inoculation of different trypanosome strains into volunteers yielded positive parasitaemia for original isolates from lion, hyaena, and Coke's hartebeest. Changing antibody titers during the course of infection in the volunteers were checked with the indirect fluorescent antibody test (IFT). The BIIT WAs reliable (consistently positive) for cloned T. b. rhodesiense. When testing T. b. brucei, the BIIT results depended on the number of incubated parasites and on the parasitaemia peak number the tested trypanosomes derived from. It was further shown that the in vivo part of the BIIT is actually essential for the complete neutralization of T. b. brucei induced by the action of human plasma. Tests with trypanosomes originating from experimentally mixed T. b. rhodesiense and brucei infections gave inconsistent results. On the other hand, pure populations mixed in vitro-prior to incubation for BIIT-revealed results depending on the proportion of the 2 species: up to 20% T. b. rhodesiense gave negative, higher concentrations consistently positive results.", "contents": "Identification of T. brucei-subgroup strains isolated from game. Several T. brucei-subgroup strains isolated from game were investigated with the blood incubation infectivity test (BIIT) and in human volunteers. Original isolates and their clones derivatives were tested. In order to check the validity of the BIIT, volunteer tested clones were used under modified BIIT conditions. Inoculation of different trypanosome strains into volunteers yielded positive parasitaemia for original isolates from lion, hyaena, and Coke's hartebeest. Changing antibody titers during the course of infection in the volunteers were checked with the indirect fluorescent antibody test (IFT). The BIIT WAs reliable (consistently positive) for cloned T. b. rhodesiense. When testing T. b. brucei, the BIIT results depended on the number of incubated parasites and on the parasitaemia peak number the tested trypanosomes derived from. It was further shown that the in vivo part of the BIIT is actually essential for the complete neutralization of T. b. brucei induced by the action of human plasma. Tests with trypanosomes originating from experimentally mixed T. b. rhodesiense and brucei infections gave inconsistent results. On the other hand, pure populations mixed in vitro-prior to incubation for BIIT-revealed results depending on the proportion of the 2 species: up to 20% T. b. rhodesiense gave negative, higher concentrations consistently positive results."}
{"id": "PMID:1984", "title": "Studies on malaria and responses of Anopheles balabacensis balabacensis and Anopheles minimus to DDT residual spraying in Thailand.", "content": "Studies on malaria and on A. b. balabacensis and A. minimus responses to DDT spraying were conducted in a forested hilly area in northern Thailand. In a first phase, base-line data were collected from July 1970 to March 1972. In a second phase, the study area received five round of DDT spraying over a period of two years and at the same time all malaria infections received radical treatment. During this two-year period of field operations, entomological and epidemiological observations were continued. The studies carried out in the second phase, showed that malaria transmission decreased under the applied optimum anti-malarial measures but was not interrupted. Human ecology and population movement inside the forest, especially during the dry season, contributed to a great extent to this result. The transmission occurring in the early part of the monsoon season clearly indicates the importance of the timing of DDT spraying. A. b. balabacensis appeared to be transmitting malaria all the year round in the deep forest but only in the monsoon season in the forest fringe. The vectorial capacity of both vectors was estimated separately for indoor and outdoor populations. The pre-spraying values obtained for A. b. balabacensis were much higher thaan for A. minimus. After DDT spraying A. b. balabacensis showed a decrease in vectorial capacity estimated at 31.5 times for the indoor population and 18 times for the outdoor population. A. minimus, on the other hand, showed a much smaller decrease, estimated at 6.8 and 1.9 times for the indoor and outdoor populations respectively.", "contents": "Studies on malaria and responses of Anopheles balabacensis balabacensis and Anopheles minimus to DDT residual spraying in Thailand. Studies on malaria and on A. b. balabacensis and A. minimus responses to DDT spraying were conducted in a forested hilly area in northern Thailand. In a first phase, base-line data were collected from July 1970 to March 1972. In a second phase, the study area received five round of DDT spraying over a period of two years and at the same time all malaria infections received radical treatment. During this two-year period of field operations, entomological and epidemiological observations were continued. The studies carried out in the second phase, showed that malaria transmission decreased under the applied optimum anti-malarial measures but was not interrupted. Human ecology and population movement inside the forest, especially during the dry season, contributed to a great extent to this result. The transmission occurring in the early part of the monsoon season clearly indicates the importance of the timing of DDT spraying. A. b. balabacensis appeared to be transmitting malaria all the year round in the deep forest but only in the monsoon season in the forest fringe. The vectorial capacity of both vectors was estimated separately for indoor and outdoor populations. The pre-spraying values obtained for A. b. balabacensis were much higher thaan for A. minimus. After DDT spraying A. b. balabacensis showed a decrease in vectorial capacity estimated at 31.5 times for the indoor population and 18 times for the outdoor population. A. minimus, on the other hand, showed a much smaller decrease, estimated at 6.8 and 1.9 times for the indoor and outdoor populations respectively."}
{"id": "PMID:1985", "title": "[Ecological study of Ixodes ricinus (Linn\u00e9, 1758) (Acarina, Ixodoides) in southeastern France].", "content": "Ixodes ricinus (LINNE, 1758) is being surveyed in the northern Alp and the Jura mountains. This species, quite often found in the mesophilous forests of the hills, preferably takes root in the forest clusters, where there is a mull type mild humus often covered with an abundant litter. Such plant layers maintain a high degree of moisture, which beneficially affects this species. Examinations performed for three years in a southern Jura's resort allow for securing a preliminary approximation as regards the seasonal population variations.", "contents": "[Ecological study of Ixodes ricinus (Linn\u00e9, 1758) (Acarina, Ixodoides) in southeastern France]. Ixodes ricinus (LINNE, 1758) is being surveyed in the northern Alp and the Jura mountains. This species, quite often found in the mesophilous forests of the hills, preferably takes root in the forest clusters, where there is a mull type mild humus often covered with an abundant litter. Such plant layers maintain a high degree of moisture, which beneficially affects this species. Examinations performed for three years in a southern Jura's resort allow for securing a preliminary approximation as regards the seasonal population variations."}
{"id": "PMID:1986", "title": "The micro-organisms of tsetse flies.", "content": "Micro-organisms from tsetse fly mycetomes were maintained in culture, where they were more pleomorphic than in the mycetomes, but were in some cases very similar to those observed in ovaries by other authors. Agglutination tests on the cultured forms indicated in affinity to Rickettsia. They were sensitive to antibiotics introduced by feeding flies on hosts treated with Ampicillin; this reduced the longevity and fecundity of the tsetse flies and appeared to disturb normal digestion of bloodmeals.", "contents": "The micro-organisms of tsetse flies. Micro-organisms from tsetse fly mycetomes were maintained in culture, where they were more pleomorphic than in the mycetomes, but were in some cases very similar to those observed in ovaries by other authors. Agglutination tests on the cultured forms indicated in affinity to Rickettsia. They were sensitive to antibiotics introduced by feeding flies on hosts treated with Ampicillin; this reduced the longevity and fecundity of the tsetse flies and appeared to disturb normal digestion of bloodmeals."}
{"id": "PMID:1987", "title": "The histopathology of experimental disease produced in mice infected with Trypanosoma vivax.", "content": "An acute form of trypanosomiasis (course of disease 4 to 8 days) was produced in mice experimentally infected with a strain of T. vivax. The features of the disease were: a parasitemia which appeared to increase exponentially from 23.8 to 243.6 times 10(6) trypanosomes per ml within the last 24 hours of the disease; anaemia was not severe in the disease in mice; the basic histological lesion was generalized fibrin thrombus formation in the blood vessels of the heart, lung, spleen and brain; trypanosome enboli were present in the brain, spleen and liver of infected mice. The disease in mice could prove a useful model in studies of the pathogenesis of acute trypanosomiasis and also in studies in the mechanism of generalized intravascular coagulation.", "contents": "The histopathology of experimental disease produced in mice infected with Trypanosoma vivax. An acute form of trypanosomiasis (course of disease 4 to 8 days) was produced in mice experimentally infected with a strain of T. vivax. The features of the disease were: a parasitemia which appeared to increase exponentially from 23.8 to 243.6 times 10(6) trypanosomes per ml within the last 24 hours of the disease; anaemia was not severe in the disease in mice; the basic histological lesion was generalized fibrin thrombus formation in the blood vessels of the heart, lung, spleen and brain; trypanosome enboli were present in the brain, spleen and liver of infected mice. The disease in mice could prove a useful model in studies of the pathogenesis of acute trypanosomiasis and also in studies in the mechanism of generalized intravascular coagulation."}
{"id": "PMID:1988", "title": "Lipase and unspecific esterase activity in the fat body of Aedes aegypti L.", "content": "In the fat body of Aedes aegypti a very high unspecific esterase activity and a low lipolytic activity was found. The electrophoretic isozyme patterns of the unspecific esterases show only few changes in the different physiological stages. The activity of the unspecific esterases as well as of the lipase is especially high in young sugar fed and in blood fed mosquitoes which points to special energy requirements in these stages. The role of the unspecific esterases is discussed.", "contents": "Lipase and unspecific esterase activity in the fat body of Aedes aegypti L. In the fat body of Aedes aegypti a very high unspecific esterase activity and a low lipolytic activity was found. The electrophoretic isozyme patterns of the unspecific esterases show only few changes in the different physiological stages. The activity of the unspecific esterases as well as of the lipase is especially high in young sugar fed and in blood fed mosquitoes which points to special energy requirements in these stages. The role of the unspecific esterases is discussed."}
{"id": "PMID:1989", "title": "Effect of adsorbents on IgM and IgG measles antibodies.", "content": "Sera from rabbits immunized with L-16 measles virus absorded with monkey blood cells; kaolin and blood cells; and MnCl2 and heparin were examined in haemagglutination inhibition (HI) and neutralization tests. Kaolin and MnCl2 adsorbed primarily HI IgM antibodies from the early immunization period. The adsorbents used had no influence on HI and neutralization IgG antibodies. Human convalescent serum gave similar results, i.e. only IgG antibodies were found and they were not affected by kaolin and MnCl2 with heparin.", "contents": "Effect of adsorbents on IgM and IgG measles antibodies. Sera from rabbits immunized with L-16 measles virus absorded with monkey blood cells; kaolin and blood cells; and MnCl2 and heparin were examined in haemagglutination inhibition (HI) and neutralization tests. Kaolin and MnCl2 adsorbed primarily HI IgM antibodies from the early immunization period. The adsorbents used had no influence on HI and neutralization IgG antibodies. Human convalescent serum gave similar results, i.e. only IgG antibodies were found and they were not affected by kaolin and MnCl2 with heparin."}
{"id": "PMID:1990", "title": "Correlation between molecular size and interferon- inducing activity of poly I:C.", "content": "Electron microscopy showed that commerical poly I: C consisted of molecules varying in length from less than 0.05 nm to more than 5 nm and also in morphology . To clarify the relationship between its molecular size and interferon-inducing activity, poly I: C was sonicated or fractionated by sucrose density gradient centrifugation, and the molecular length distribution and interferon-inducing activity of each preparation was determined in vivo and in vitro. The results showed that (1) poly I : C molecules 0.1-0.3 nm long were the most effective for interferon induction; (2) sonication of poly I : C reduced its molecular length and also the interferon-inducing activity, the degree of reduction varying in different fractions; and (3) the interferon-inducing activity of poly I: C of 0.1-0.3 nm obtained by sucrose density gradient centrifugation was higher than that poly I: C of corresponding length prepared by sonication.", "contents": "Correlation between molecular size and interferon- inducing activity of poly I:C. Electron microscopy showed that commerical poly I: C consisted of molecules varying in length from less than 0.05 nm to more than 5 nm and also in morphology . To clarify the relationship between its molecular size and interferon-inducing activity, poly I: C was sonicated or fractionated by sucrose density gradient centrifugation, and the molecular length distribution and interferon-inducing activity of each preparation was determined in vivo and in vitro. The results showed that (1) poly I : C molecules 0.1-0.3 nm long were the most effective for interferon induction; (2) sonication of poly I : C reduced its molecular length and also the interferon-inducing activity, the degree of reduction varying in different fractions; and (3) the interferon-inducing activity of poly I: C of 0.1-0.3 nm obtained by sucrose density gradient centrifugation was higher than that poly I: C of corresponding length prepared by sonication."}
{"id": "PMID:1991", "title": "Distribution of Lednice (Yaba 1) virus in the chick embryo.", "content": "Distribution of Lednice (Yaba 1) virus antigen (LVA) was followed by immunofluorescene (IF) in chick embryos inoculated into the yolk sacs. Positive fluorescence of LVA was observed in neurons and neuroblasts of the developing brain, spinal cord and spinal ganglia as well as in skeletal muscles, heart muscle, vascular endothelium and lung mesenchyma. In the yolk sac, foci of specific fluorescence were occasionally seen in endothelium cells of vessels and in islands of extraembryonic haematopoesis. At sites corresponding to the occurrence of LVA, extensive oedema was accompanied by extravazation of erythrocytes and accumulation of white blood cells. The nature of tissues in which the virus replicates was discussed from the point of view of LVA distribution and the morphological lesions observed.", "contents": "Distribution of Lednice (Yaba 1) virus in the chick embryo. Distribution of Lednice (Yaba 1) virus antigen (LVA) was followed by immunofluorescene (IF) in chick embryos inoculated into the yolk sacs. Positive fluorescence of LVA was observed in neurons and neuroblasts of the developing brain, spinal cord and spinal ganglia as well as in skeletal muscles, heart muscle, vascular endothelium and lung mesenchyma. In the yolk sac, foci of specific fluorescence were occasionally seen in endothelium cells of vessels and in islands of extraembryonic haematopoesis. At sites corresponding to the occurrence of LVA, extensive oedema was accompanied by extravazation of erythrocytes and accumulation of white blood cells. The nature of tissues in which the virus replicates was discussed from the point of view of LVA distribution and the morphological lesions observed."}
{"id": "PMID:1992", "title": "Serological differences between some isolates of bean yellow mosaic virus.", "content": "The degree of serological relatedness of three isolates of bean yellow mosaic virus (BYMV) was studied. One common antigenic group (m) was demonstrated in all 3 isolates. In addition, another antigenic group (a) was demonstrated in the isolate FvM1. This group was absent from the isolates TpM3 and TpM11, in which the antigenic group n was found. Antisera to the 3 isolates contained the corresponding antibody groups. The antibody group (M) shared by all 3 BYMV isolates was present in the FvM1 antiserum in a level only a little higher than the second antibody group (A). Antisera to TpM3 and TpM11 isolates showed only a low titre of M antibody, while the second antibody group (N) reached titres from 512 to 1024. Cross-absorption tests revealed serological identity of both isolates of the \"necrotic type\" (TpM3 and TpM11) and allowed to estimate the degree of their serological relatedness to representatives of the \"mosaic type\" isolates of BYMV (FvM1).", "contents": "Serological differences between some isolates of bean yellow mosaic virus. The degree of serological relatedness of three isolates of bean yellow mosaic virus (BYMV) was studied. One common antigenic group (m) was demonstrated in all 3 isolates. In addition, another antigenic group (a) was demonstrated in the isolate FvM1. This group was absent from the isolates TpM3 and TpM11, in which the antigenic group n was found. Antisera to the 3 isolates contained the corresponding antibody groups. The antibody group (M) shared by all 3 BYMV isolates was present in the FvM1 antiserum in a level only a little higher than the second antibody group (A). Antisera to TpM3 and TpM11 isolates showed only a low titre of M antibody, while the second antibody group (N) reached titres from 512 to 1024. Cross-absorption tests revealed serological identity of both isolates of the \"necrotic type\" (TpM3 and TpM11) and allowed to estimate the degree of their serological relatedness to representatives of the \"mosaic type\" isolates of BYMV (FvM1)."}
{"id": "PMID:1993", "title": "Enhancement of the antigenic activity and virulence of the vaccine strain E of Rickettsia prow azeki by passages in cell culture.", "content": "Changes in the biological properties of the vaccine strain E of Rickettsia prowazeki occurred upon cultivation of A1 (human amnion) cells infected with this strain. In the course of passages of these cells the antigenic activity and virulence of the rickettsia increased. The changes were observed in 10 out of 22 cell cultures examined: in 6 cultures there was an increase in the antigenic activity and in 4 both in the antigenic activity and in virulence. The time of the occurrence of these changes in the rickettsial populations varied from 12-18 to 53-102 days of passage of the infected cells.", "contents": "Enhancement of the antigenic activity and virulence of the vaccine strain E of Rickettsia prow azeki by passages in cell culture. Changes in the biological properties of the vaccine strain E of Rickettsia prowazeki occurred upon cultivation of A1 (human amnion) cells infected with this strain. In the course of passages of these cells the antigenic activity and virulence of the rickettsia increased. The changes were observed in 10 out of 22 cell cultures examined: in 6 cultures there was an increase in the antigenic activity and in 4 both in the antigenic activity and in virulence. The time of the occurrence of these changes in the rickettsial populations varied from 12-18 to 53-102 days of passage of the infected cells."}
{"id": "PMID:1994", "title": "Immunization against Q-fever of naturally infected dairy cows.", "content": "Dairy cows infected naturally with Coxiella burnetii as evidenced either by presence of phase II agglutinating antibodies in the blood or by shedding C. burnetii in the milk, were vaccinated subcutaneously with formalin-killed phase I C. burnetii organisms. Attempts to demonstrate C. burnetii in the milk of vaccinated dairy cows 47 days after vaccination were negative, while continuous shedding of C. burnetii in the milk of control non-vaccinated dairy cows was repeatedly demonstrated in the course of 123 days (period of investigation). No harmful systemic reaction following vaccination was observed.", "contents": "Immunization against Q-fever of naturally infected dairy cows. Dairy cows infected naturally with Coxiella burnetii as evidenced either by presence of phase II agglutinating antibodies in the blood or by shedding C. burnetii in the milk, were vaccinated subcutaneously with formalin-killed phase I C. burnetii organisms. Attempts to demonstrate C. burnetii in the milk of vaccinated dairy cows 47 days after vaccination were negative, while continuous shedding of C. burnetii in the milk of control non-vaccinated dairy cows was repeatedly demonstrated in the course of 123 days (period of investigation). No harmful systemic reaction following vaccination was observed."}
{"id": "PMID:1995", "title": "Characterization of Nigerian strains of West Nile virus by plaque formation.", "content": "Seven strains of West nile virus isolated in Nigeria were investigated for their ability to form plaques in monkey kidney cell monolayers. Five strains antigenically related to one another produced plaques of about the same size 3 to 4 days after the addition of the overlay medium. The two other strains closely related to each other produced no plaques. Their inability to produce plaques was regarded as a significant characteristic of the intratypic group to which the two strains belong.", "contents": "Characterization of Nigerian strains of West Nile virus by plaque formation. Seven strains of West nile virus isolated in Nigeria were investigated for their ability to form plaques in monkey kidney cell monolayers. Five strains antigenically related to one another produced plaques of about the same size 3 to 4 days after the addition of the overlay medium. The two other strains closely related to each other produced no plaques. Their inability to produce plaques was regarded as a significant characteristic of the intratypic group to which the two strains belong."}
{"id": "PMID:1996", "title": "Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation.", "content": "Complement-requiring neutralizing antibodies to herpes simplex type 1 virus (HSV 1) in titres from 2 to greater than 16 were detected in the cerebrospinal fluid (CSF) of 47% senile patients with various forms of dementia, but in none of mentally retarded adolescents and adults suffering from various neurologidal diseases. Also the incidence of HSV 1 serum antibodies in elevated titres (larger than or equal to 512) was increased in senile demented patients (61%) as compared with persons in normal senium (31%), normal adults (15%), mentally retarded adolescents (17%) and prisoned felons with low IQ (45-47%).", "contents": "Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation. Complement-requiring neutralizing antibodies to herpes simplex type 1 virus (HSV 1) in titres from 2 to greater than 16 were detected in the cerebrospinal fluid (CSF) of 47% senile patients with various forms of dementia, but in none of mentally retarded adolescents and adults suffering from various neurologidal diseases. Also the incidence of HSV 1 serum antibodies in elevated titres (larger than or equal to 512) was increased in senile demented patients (61%) as compared with persons in normal senium (31%), normal adults (15%), mentally retarded adolescents (17%) and prisoned felons with low IQ (45-47%)."}
{"id": "PMID:2001", "title": "On the problem of oncogene of tumour viruses.", "content": "The approach to the problem of oncogenesis of tumorigenic viruses is compared and analyzed from the position of the Altshtein-Vogt hypothesis and from that of the general theory of oncogenesis advanced by the present author. In contrast to the hypothesis of Altshtein-Vogt dealing mainly with the problem of oncogene origin, the general theory of oncogenesis not only defines concretely the origin of the oncogene and the essence of its product, but also makes it possible to understand why, when and how integration of the oncogene with the genome of the cell leads to the transformation of the cell into a benign cell and when into a malignant tumour cell. An analysis of the essence of the \"oncogene position effect\" from this standpoint shows that an integration, similar in its mechanism but differing in polarity, of the genome of other viruses with the cell genome should lead to the formation of a corresponding antiviral stable (life-long) immunity or also to the emergence of pseudoautoimmune disease of the type caused by \"slow\" viruses.", "contents": "On the problem of oncogene of tumour viruses. The approach to the problem of oncogenesis of tumorigenic viruses is compared and analyzed from the position of the Altshtein-Vogt hypothesis and from that of the general theory of oncogenesis advanced by the present author. In contrast to the hypothesis of Altshtein-Vogt dealing mainly with the problem of oncogene origin, the general theory of oncogenesis not only defines concretely the origin of the oncogene and the essence of its product, but also makes it possible to understand why, when and how integration of the oncogene with the genome of the cell leads to the transformation of the cell into a benign cell and when into a malignant tumour cell. An analysis of the essence of the \"oncogene position effect\" from this standpoint shows that an integration, similar in its mechanism but differing in polarity, of the genome of other viruses with the cell genome should lead to the formation of a corresponding antiviral stable (life-long) immunity or also to the emergence of pseudoautoimmune disease of the type caused by \"slow\" viruses."}
{"id": "PMID:2004", "title": "Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.", "content": "Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.", "contents": "Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs."}
{"id": "PMID:2006", "title": "Nutrition education in the medical school curriculum: a proposal for action: a curriculum design.", "content": "Nutrition has been traditionally taught in medical schools with emphasis on clinical management of disease states with modified diets. However, the science of nutrition can no longer be considered only in terms of the diagnosis and treatment of nutritional deficiency diseases. Prevention of disease-care rather than cure-must be emphasized. Using the nutrition concepts that evolved from the 1972 Williamsburg Conference encompassing the science and the sociology of nutrition, the author offers a proposal for action-a sequential nutrition curriculum design for years, I, II, and III of undergraduate medical education based on the experiences of the Nutrition Division, Department of Community Medicine, Mount Sinai School of Medicine-City University of New York.", "contents": "Nutrition education in the medical school curriculum: a proposal for action: a curriculum design. Nutrition has been traditionally taught in medical schools with emphasis on clinical management of disease states with modified diets. However, the science of nutrition can no longer be considered only in terms of the diagnosis and treatment of nutritional deficiency diseases. Prevention of disease-care rather than cure-must be emphasized. Using the nutrition concepts that evolved from the 1972 Williamsburg Conference encompassing the science and the sociology of nutrition, the author offers a proposal for action-a sequential nutrition curriculum design for years, I, II, and III of undergraduate medical education based on the experiences of the Nutrition Division, Department of Community Medicine, Mount Sinai School of Medicine-City University of New York."}
{"id": "PMID:2007", "title": "Management of life-threatening asthma with intravenous isoproterenol infusions.", "content": "Thirty-four patients with life-threatening childhood status asthmaticus were treated with intravenous isoproterenol infusions. Twenty-seven responded favorably; seven failed to respond and underwent mechanical ventilation. Intravenously administered isoporterenol was a useful therapeutic adjunct in the treatment of these severe attacks. Complications in these cases were rare, but cardiac arrhythmia, rebound bronchospasm, and acute mobilization of secretions need to be considered. Further evaluation of the efficacy of intravenous infusions of isoproterenol in status asthmaticus would be valuable.", "contents": "Management of life-threatening asthma with intravenous isoproterenol infusions. Thirty-four patients with life-threatening childhood status asthmaticus were treated with intravenous isoproterenol infusions. Twenty-seven responded favorably; seven failed to respond and underwent mechanical ventilation. Intravenously administered isoporterenol was a useful therapeutic adjunct in the treatment of these severe attacks. Complications in these cases were rare, but cardiac arrhythmia, rebound bronchospasm, and acute mobilization of secretions need to be considered. Further evaluation of the efficacy of intravenous infusions of isoproterenol in status asthmaticus would be valuable."}
{"id": "PMID:2008", "title": "Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and histopathological changes.", "content": "To evaluate responses to medical therapy in ulcerative colitis, rectal biopsies of patients with active untreated disease, individuals with positive and negative sigmoidoscopic findings treated with salicylazosulfapyridine, prednisone and 6-mercaptopurine, alone and in combinations and noncolitis controls were compared histologically. Predominant histological observations were analyzed statistically. There were fewer crypt abscesses but more mucosal edema after all forms of therapy. Quantitative histopathological analysis failed to demonstrate that the response to one drug was significantly different from another.", "contents": "Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and histopathological changes. To evaluate responses to medical therapy in ulcerative colitis, rectal biopsies of patients with active untreated disease, individuals with positive and negative sigmoidoscopic findings treated with salicylazosulfapyridine, prednisone and 6-mercaptopurine, alone and in combinations and noncolitis controls were compared histologically. Predominant histological observations were analyzed statistically. There were fewer crypt abscesses but more mucosal edema after all forms of therapy. Quantitative histopathological analysis failed to demonstrate that the response to one drug was significantly different from another."}
{"id": "PMID:2009", "title": "Biochemical and electrophoretic studies of erythrocyte pyridoxine kinase in white and black Americans.", "content": "The mean PNK activity in red blood cells from black subjects was only about 40% of that in whites. Among 51 whites examined, one was found to have enzyme deficiency. The estimated gene frequencies for PNKH (the common allele in whites which codes for higher enzyme activity) and PNKL (the common allele in blacks which codes for lower enzyme activity) were .35 and .65, respectively, for black donors, and .81 and .19, respectively, for white donors, The variant enzyme in persons with enzyme deficiency was associated with an increased rate of degradation in red cells during aging. No other biochemical or electrophoretic differences were detected.", "contents": "Biochemical and electrophoretic studies of erythrocyte pyridoxine kinase in white and black Americans. The mean PNK activity in red blood cells from black subjects was only about 40% of that in whites. Among 51 whites examined, one was found to have enzyme deficiency. The estimated gene frequencies for PNKH (the common allele in whites which codes for higher enzyme activity) and PNKL (the common allele in blacks which codes for lower enzyme activity) were .35 and .65, respectively, for black donors, and .81 and .19, respectively, for white donors, The variant enzyme in persons with enzyme deficiency was associated with an increased rate of degradation in red cells during aging. No other biochemical or electrophoretic differences were detected."}
{"id": "PMID:2010", "title": "Use of the latent image technique to develop and evaluate problem-solving skills.", "content": "This project involved designing, developing and evaluating a simulation module, utilizing the latent image technique. The general topic chosen for this simulation was the laboratory characterization of anemias. Target learner populations included medical technology students, physician assistant students, and pathology residents. Members of all three groups participated in the evaluation of the module and responded to its use in varied settings.", "contents": "Use of the latent image technique to develop and evaluate problem-solving skills. This project involved designing, developing and evaluating a simulation module, utilizing the latent image technique. The general topic chosen for this simulation was the laboratory characterization of anemias. Target learner populations included medical technology students, physician assistant students, and pathology residents. Members of all three groups participated in the evaluation of the module and responded to its use in varied settings."}
{"id": "PMID:2011", "title": "Review of drug treatment for Down's syndrome persons.", "content": "A review of drug treatment for Down's syndrome individuals was presented. Drugs used to modify behavior, as well as drugs used with the goal of affecting cognitive processes, were discussed. Some observations were offered as to the effectiveness of past and current drugs on Down's syndrome and some methodological problems relating to drug studies presented. There have not been any drugs that have demonstrated remarkable improvement in the status of Down's syndrome individuals that have been widely accepted as effective.", "contents": "Review of drug treatment for Down's syndrome persons. A review of drug treatment for Down's syndrome individuals was presented. Drugs used to modify behavior, as well as drugs used with the goal of affecting cognitive processes, were discussed. Some observations were offered as to the effectiveness of past and current drugs on Down's syndrome and some methodological problems relating to drug studies presented. There have not been any drugs that have demonstrated remarkable improvement in the status of Down's syndrome individuals that have been widely accepted as effective."}
{"id": "PMID:2012", "title": "Development of a special electrode for continuous subcutaneous pH measurement in the infant scalp.", "content": "Using a combined special glass electrode it is possible to monitor pH ratios and pH variation in the subcutaneous tissue of the infant scalp continuously. Tests on a normal sample of newborn babies immediately after birth showed a significant correlation between tissue pH and capillary blood pH, with the trend of pH variation being broadly similar in both measurement media.", "contents": "Development of a special electrode for continuous subcutaneous pH measurement in the infant scalp. Using a combined special glass electrode it is possible to monitor pH ratios and pH variation in the subcutaneous tissue of the infant scalp continuously. Tests on a normal sample of newborn babies immediately after birth showed a significant correlation between tissue pH and capillary blood pH, with the trend of pH variation being broadly similar in both measurement media."}
{"id": "PMID:2013", "title": "Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial.", "content": "We conducted a controlled, prospective trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate (NaHCO3) and salt-poor albumin into high-risk, premature infants in the first 2 hours of life. Fifty-three infants, randomized into one of four treatment groups, received 8 ml. per kilogram of a solution containing either (A) glucose in water, (B) salt-poor albumin, (C) NaHCO3, or (D) a combination of albumin and NaHCO3. After the initial infusion, the babies received no colloid or alkali solutions until 4 hours of age. We managed them supportively with warmth, appropriate oxygen administration, isotonic fluid infusion, and close monitoring. Among the infants who received alkali, 14 of 26 acquired the respiratory distress syndrome (RDS), 11 died, and four had intracranial hemorrhage. Among babies who received no alkali, RDS occurred in 11 of 27, 5 died, and none had intracranial hemorrhage. These results do not support the common practice of rapidly infusing NaHCO3 into high-risk, premature infants, and they suggest that the early management of such infants needs renewed critical evaluation.", "contents": "Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial. We conducted a controlled, prospective trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate (NaHCO3) and salt-poor albumin into high-risk, premature infants in the first 2 hours of life. Fifty-three infants, randomized into one of four treatment groups, received 8 ml. per kilogram of a solution containing either (A) glucose in water, (B) salt-poor albumin, (C) NaHCO3, or (D) a combination of albumin and NaHCO3. After the initial infusion, the babies received no colloid or alkali solutions until 4 hours of age. We managed them supportively with warmth, appropriate oxygen administration, isotonic fluid infusion, and close monitoring. Among the infants who received alkali, 14 of 26 acquired the respiratory distress syndrome (RDS), 11 died, and four had intracranial hemorrhage. Among babies who received no alkali, RDS occurred in 11 of 27, 5 died, and none had intracranial hemorrhage. These results do not support the common practice of rapidly infusing NaHCO3 into high-risk, premature infants, and they suggest that the early management of such infants needs renewed critical evaluation."}
{"id": "PMID:2014", "title": "Effect of pH on ionic exchange and function in rat and rabbit myocardium.", "content": "The effects of pH variation on ionic exchange and mechanical function were studied in the arterially perfused rat and rabbit septa. The pH and PCO2 of the control perfusate were 7.40 and 39 mmHg, respectively. In the rabbit septum a metabolic acidosis (pH equals 6.82, PCO2 equals 39 mmHg) caused a loss of 16% of control tension in 12 min. Na+ and K+ exchange were unaltered. A comparable respiratory acidosis (pH equals 6.81, PCO2 equals 159 mmHg) caused a 51% loss of tension in 2 min. Na+ exchange was unaltered but K+ efflux fell from 8.9 +/- 0.6 (mean +/- SE) to 4.9 +/- 0.3 mmol/kg dry wt per min (P less than 0.001, n equals 10). A net gain of K+ of 16.9 +/- 1.7 (n equals 14) mmol/kg dry wt occurred and was attributable to a delayed fall in K+ influx relative to efflux over 15 min. The net gain could not be mimicked by epinephrine administration or blocked by propranolol and was absent in the beating rat septum and the quiescent rabbit septum. These results suggest that the net uptake of K+, which appears to be dependent on a period of depolarization, and the changes of contractility are controlled by the H+ ion concentration at a cellular site whose exchange with the extracellular space is characterized by a considerable restriction of diffusion. Changes of contractility are not related to the net uptake of K+.", "contents": "Effect of pH on ionic exchange and function in rat and rabbit myocardium. The effects of pH variation on ionic exchange and mechanical function were studied in the arterially perfused rat and rabbit septa. The pH and PCO2 of the control perfusate were 7.40 and 39 mmHg, respectively. In the rabbit septum a metabolic acidosis (pH equals 6.82, PCO2 equals 39 mmHg) caused a loss of 16% of control tension in 12 min. Na+ and K+ exchange were unaltered. A comparable respiratory acidosis (pH equals 6.81, PCO2 equals 159 mmHg) caused a 51% loss of tension in 2 min. Na+ exchange was unaltered but K+ efflux fell from 8.9 +/- 0.6 (mean +/- SE) to 4.9 +/- 0.3 mmol/kg dry wt per min (P less than 0.001, n equals 10). A net gain of K+ of 16.9 +/- 1.7 (n equals 14) mmol/kg dry wt occurred and was attributable to a delayed fall in K+ influx relative to efflux over 15 min. The net gain could not be mimicked by epinephrine administration or blocked by propranolol and was absent in the beating rat septum and the quiescent rabbit septum. These results suggest that the net uptake of K+, which appears to be dependent on a period of depolarization, and the changes of contractility are controlled by the H+ ion concentration at a cellular site whose exchange with the extracellular space is characterized by a considerable restriction of diffusion. Changes of contractility are not related to the net uptake of K+."}
{"id": "PMID:2015", "title": "Acid-base balance in amphibian gastric mucosa.", "content": "It has been established that H+ secretion can be maintained in frog stomach in the absence of exogenous CO2 by using a nutrient bathing fluid containing 25 mM H2PO4 (pH approximately equal to 4.5) or by lowering the pH of a nonbuffered nutrient solution to about 3.0-3.6. Exogenous CO2 in the presence of these nutrient solutions uniformly caused a marked decrease in H+ secretion, PD, adn short-circuit current (Isc) and an increase in transmucosal resistance (R). Elevation of nutrient [k+] to 83 mM reduced R significantly but transiently without change in H+ when nutrient pH less than 5.0, whereas R returned to base line and H+ increased when nutrient pH greater than 5.0. Acidification of the nutrient medium in the presence of exogenous CO2 results in inhibition of the secretory pump, probably by decreasing intracellular pH, and also interferes with conductance at the nutrient membrane. Removal of exogenous CO2 from standard bicarbonate nutrient solution reduced by 50% the H+, PD, and Isc without change in R; K+-free nutrient solutions reverse these changes in Isc and PD but not in H+. The dropping PD and rising R induced by K+-free nutrient solutions in 5% CO2 - 95% O2 are returned toward normal by 100% O2. Our findings support an important role for exogenous CO2 in maintaining normal acid-base balance in frog mucosa by acting as an acidifying agent.", "contents": "Acid-base balance in amphibian gastric mucosa. It has been established that H+ secretion can be maintained in frog stomach in the absence of exogenous CO2 by using a nutrient bathing fluid containing 25 mM H2PO4 (pH approximately equal to 4.5) or by lowering the pH of a nonbuffered nutrient solution to about 3.0-3.6. Exogenous CO2 in the presence of these nutrient solutions uniformly caused a marked decrease in H+ secretion, PD, adn short-circuit current (Isc) and an increase in transmucosal resistance (R). Elevation of nutrient [k+] to 83 mM reduced R significantly but transiently without change in H+ when nutrient pH less than 5.0, whereas R returned to base line and H+ increased when nutrient pH greater than 5.0. Acidification of the nutrient medium in the presence of exogenous CO2 results in inhibition of the secretory pump, probably by decreasing intracellular pH, and also interferes with conductance at the nutrient membrane. Removal of exogenous CO2 from standard bicarbonate nutrient solution reduced by 50% the H+, PD, and Isc without change in R; K+-free nutrient solutions reverse these changes in Isc and PD but not in H+. The dropping PD and rising R induced by K+-free nutrient solutions in 5% CO2 - 95% O2 are returned toward normal by 100% O2. Our findings support an important role for exogenous CO2 in maintaining normal acid-base balance in frog mucosa by acting as an acidifying agent."}
{"id": "PMID:2016", "title": "Effect of sodium nitrate loading on electrolyte transport by the renal tubule.", "content": "Effects of sodium nitrate were compared with sodium chloride loading on transport of electrolytes by the nephron. Maximal levels of free water clearance/clomerular filtration rate (CH2O/GFR) averaged 8.4% with nitrate loading and 14.4% with saline loading. Since ethacrynic acid and chlorothiazide exert their major natriuretic effect in the distal nephron, the increment in Na ad Cl reabsorbed beyond the proximal tubule. The administration of these agents resulted in an increase in fractional sodium excretion (CNa/GFR) of 21.1%, urinary sodium excretion (UNaV) of 1,126 mueq/min, and urinary chloride excretion (UClV) of 848 mueq/min during nitrate loading compared with an increase in CNa/GFR of 37.6%, UNaV of 2,362 mueq/min, and UClV of 2,397 mueq/min during saline loading. The smaller diuretic-induced increment in Na and Cl excretion in the nitrate studies suggests, as do the hydrated studies, that less Cl and Na are reabsorbed in the distal nephron during nitrate than saline loading. At every level of UNaV, fractional bicarbonate reabsorption was higher, urine pH was lower, and urinary potassium excretion (UKV) was higher in the nitrate studies. Thus, compared with saline loading, sodium nitrate decreases chloride and sodium reabsorption in the distal nephron. The higher hydrogen and potassium secretion in the nitrate studies may be consequent to the decreased ability of the distal nephron to reabsorb chloride.", "contents": "Effect of sodium nitrate loading on electrolyte transport by the renal tubule. Effects of sodium nitrate were compared with sodium chloride loading on transport of electrolytes by the nephron. Maximal levels of free water clearance/clomerular filtration rate (CH2O/GFR) averaged 8.4% with nitrate loading and 14.4% with saline loading. Since ethacrynic acid and chlorothiazide exert their major natriuretic effect in the distal nephron, the increment in Na ad Cl reabsorbed beyond the proximal tubule. The administration of these agents resulted in an increase in fractional sodium excretion (CNa/GFR) of 21.1%, urinary sodium excretion (UNaV) of 1,126 mueq/min, and urinary chloride excretion (UClV) of 848 mueq/min during nitrate loading compared with an increase in CNa/GFR of 37.6%, UNaV of 2,362 mueq/min, and UClV of 2,397 mueq/min during saline loading. The smaller diuretic-induced increment in Na and Cl excretion in the nitrate studies suggests, as do the hydrated studies, that less Cl and Na are reabsorbed in the distal nephron during nitrate than saline loading. At every level of UNaV, fractional bicarbonate reabsorption was higher, urine pH was lower, and urinary potassium excretion (UKV) was higher in the nitrate studies. Thus, compared with saline loading, sodium nitrate decreases chloride and sodium reabsorption in the distal nephron. The higher hydrogen and potassium secretion in the nitrate studies may be consequent to the decreased ability of the distal nephron to reabsorb chloride."}
{"id": "PMID:2017", "title": "Coronary vascular and myocardial responses to carotid body stimulation in the dog.", "content": "Coronary vascular and myocardial responses to selective hypoxic and/or hypercapnic carotid chemoreceptor stimulation were investigated in constantly ventilated, pentobarbital or urethan-chloralose anesthetized dogs. Bilaterally isolated carotid chemoreceptors were perfused with autologous blood of varying O2 and CO2 tensions via an extracorporeal lung circuit. Systemic gas tensions were unchanged. Effects of carotid chemoreceptor stimulation on coronary vascular resistance, left ventricular dP/dt, and strain-gauge arch output were studied at natural coronary blood flow with the chest closed and during constant-flow perfusion of the left common coronary artery with the chest open. Carotid chemoreceptor stimulation slightly increased left ventricular dP/dt and slightly decreased the strain-gauge arch output, while markedly increasing systemic pressure. Coronary blood flow increased; however, coronary vascular resistance wa.as not affected. These studies show that local carotid body stimulation increases coronary blood flow but has little effect on the myocardium. The increase in coronary blood flow results mainly from an increase in systemic arterial pressure. Thus these data provide little evidence for increased sympathetic activity of the heart during local stimulation of the carotid chemoreceptors with hypoxic and hypercapnic blood.", "contents": "Coronary vascular and myocardial responses to carotid body stimulation in the dog. Coronary vascular and myocardial responses to selective hypoxic and/or hypercapnic carotid chemoreceptor stimulation were investigated in constantly ventilated, pentobarbital or urethan-chloralose anesthetized dogs. Bilaterally isolated carotid chemoreceptors were perfused with autologous blood of varying O2 and CO2 tensions via an extracorporeal lung circuit. Systemic gas tensions were unchanged. Effects of carotid chemoreceptor stimulation on coronary vascular resistance, left ventricular dP/dt, and strain-gauge arch output were studied at natural coronary blood flow with the chest closed and during constant-flow perfusion of the left common coronary artery with the chest open. Carotid chemoreceptor stimulation slightly increased left ventricular dP/dt and slightly decreased the strain-gauge arch output, while markedly increasing systemic pressure. Coronary blood flow increased; however, coronary vascular resistance wa.as not affected. These studies show that local carotid body stimulation increases coronary blood flow but has little effect on the myocardium. The increase in coronary blood flow results mainly from an increase in systemic arterial pressure. Thus these data provide little evidence for increased sympathetic activity of the heart during local stimulation of the carotid chemoreceptors with hypoxic and hypercapnic blood."}
{"id": "PMID:2018", "title": "Oxygenation of frog gastric mucosa in vitro.", "content": "We have recently shown that 5% CO2/95% O2 in the serosal bathing solution, with 100% O2 in the mucosal solution, results in CO2-diffusion limitation of acid secretion in bullfrog gastric mucosa. Changing to 10% CO2/90% 02 on both surfaces doubles the acid secretory rate. We calculate that, were the rate of oxygen consumption to increase significantly as a result of secretory stimulation, the tissue would now be oxygen limited. This prediction is tested by raising the P02 by increasing the total pressure in a hyperbaric chamber. Since no change in acid secretory rate or potential difference was observed upon changing from PO2 = 0.9 to PO2 = 1.9 atm, we conclude that the tissue is not O2 limited at normal pressure. Decreasing PO2 below 0.9 atm, by contrast, decreases the acid secretory rate and raises both PD and resistance. We infer that the rate of oxygen consumption did not rise significantly when acid secretion was increased by supplying sufficient CO2.", "contents": "Oxygenation of frog gastric mucosa in vitro. We have recently shown that 5% CO2/95% O2 in the serosal bathing solution, with 100% O2 in the mucosal solution, results in CO2-diffusion limitation of acid secretion in bullfrog gastric mucosa. Changing to 10% CO2/90% 02 on both surfaces doubles the acid secretory rate. We calculate that, were the rate of oxygen consumption to increase significantly as a result of secretory stimulation, the tissue would now be oxygen limited. This prediction is tested by raising the P02 by increasing the total pressure in a hyperbaric chamber. Since no change in acid secretory rate or potential difference was observed upon changing from PO2 = 0.9 to PO2 = 1.9 atm, we conclude that the tissue is not O2 limited at normal pressure. Decreasing PO2 below 0.9 atm, by contrast, decreases the acid secretory rate and raises both PD and resistance. We infer that the rate of oxygen consumption did not rise significantly when acid secretion was increased by supplying sufficient CO2."}
{"id": "PMID:2019", "title": "Mechanisms of disposal of acid and alkali in rabbit duodenum.", "content": "Stripped duodenal mucosa of rabbits was mounted in Ussing chambers containing a Ringer solution gassed with 100% O2. The disappearance of acid or alkali from the mucosal solution of short-circuited tissue was measured with a pH stat while the serosal pH was kept at 7.4. The duodenum rapidly disposed of both acid and alkali; neither property was altered by gassing with N2 while iodoacetate was in the perfusing solutions. Prevention of release of CO2 from the mucosal chamber obliterated the early rapid phase of acid disposal by the mucosa while a similar maneuver in the serosal chamber increased the appearance of serosal acid without altering the rate of acid disposal. Gut sacs of rabbit duodenum in vitro and in vivo showed a positive correlation between acid disposal and the rate of luminal CO2 production. While acid disposal progressively decreased with time for the in vitro gut sacs, the in vivo gut sac showed no fatigue in this respect. Luminal acidification in the Ussing chamber was associated with a profound reduction in short-circuit current (Isc), partially reversible by elevation of the mucosal pH but not by luminal glucose. Our data suggest that acid disposal occurs in part by intraluminal neutralization and in part by diffusion into the mucosa.", "contents": "Mechanisms of disposal of acid and alkali in rabbit duodenum. Stripped duodenal mucosa of rabbits was mounted in Ussing chambers containing a Ringer solution gassed with 100% O2. The disappearance of acid or alkali from the mucosal solution of short-circuited tissue was measured with a pH stat while the serosal pH was kept at 7.4. The duodenum rapidly disposed of both acid and alkali; neither property was altered by gassing with N2 while iodoacetate was in the perfusing solutions. Prevention of release of CO2 from the mucosal chamber obliterated the early rapid phase of acid disposal by the mucosa while a similar maneuver in the serosal chamber increased the appearance of serosal acid without altering the rate of acid disposal. Gut sacs of rabbit duodenum in vitro and in vivo showed a positive correlation between acid disposal and the rate of luminal CO2 production. While acid disposal progressively decreased with time for the in vitro gut sacs, the in vivo gut sac showed no fatigue in this respect. Luminal acidification in the Ussing chamber was associated with a profound reduction in short-circuit current (Isc), partially reversible by elevation of the mucosal pH but not by luminal glucose. Our data suggest that acid disposal occurs in part by intraluminal neutralization and in part by diffusion into the mucosa."}
{"id": "PMID:2021", "title": "Maintenance antipsychotic therapy: is the cure worse than the disease?", "content": "The serious long-term complications of maintenance antipsychotic therapy led the authors to undertake a critical review of outpatient withdrawal studies. Key findings included the following: 1) for a least 40% of outpatient schizophrenics, drugs seem to be essential for survival in the community; 2) the majority of patients who relapse after drug withdrawal recompensate fairly rapidly upon reinstitution of antipsychotic drug therapy; 3) placebo survivors seem to function as well as drug survivors--thus the benefit of maintenance drug therapy appears to be prevention of relapse; and 4) some cases of early relapse after drug withdrawal may be due to dyskinesia rather than psychotic decompensation. The authors urge clinicians to evaluate each patient on maintenance antipsychotic therapy in terms of feasibility of drug withdrawal and offer practical guidelines for withdrawal and subsequent management.", "contents": "Maintenance antipsychotic therapy: is the cure worse than the disease? The serious long-term complications of maintenance antipsychotic therapy led the authors to undertake a critical review of outpatient withdrawal studies. Key findings included the following: 1) for a least 40% of outpatient schizophrenics, drugs seem to be essential for survival in the community; 2) the majority of patients who relapse after drug withdrawal recompensate fairly rapidly upon reinstitution of antipsychotic drug therapy; 3) placebo survivors seem to function as well as drug survivors--thus the benefit of maintenance drug therapy appears to be prevention of relapse; and 4) some cases of early relapse after drug withdrawal may be due to dyskinesia rather than psychotic decompensation. The authors urge clinicians to evaluate each patient on maintenance antipsychotic therapy in terms of feasibility of drug withdrawal and offer practical guidelines for withdrawal and subsequent management."}
{"id": "PMID:2022", "title": "Task delegation to physician extenders--some comparisons.", "content": "This study uses a task delegation questionnaire to compare 1973 physician extender practices in seven primary care-oriented sites with a physician attitude survey made in 1969. One additional site using no physician extenders was included as a control. The study involves both major types of physician extenders (physician assistants and nurse practitioners) in ambulatory practices with at least one year of experience in using such personnel. With minor exceptions, actual task delegation patterns conform with the 1969 attitudes of physicians as to which tasks \"could and should\" be delegated to physician extenders.", "contents": "Task delegation to physician extenders--some comparisons. This study uses a task delegation questionnaire to compare 1973 physician extender practices in seven primary care-oriented sites with a physician attitude survey made in 1969. One additional site using no physician extenders was included as a control. The study involves both major types of physician extenders (physician assistants and nurse practitioners) in ambulatory practices with at least one year of experience in using such personnel. With minor exceptions, actual task delegation patterns conform with the 1969 attitudes of physicians as to which tasks \"could and should\" be delegated to physician extenders."}
{"id": "PMID:2023", "title": "Chest roentgenography as a window to the diagnosis of Takayasu's arteritis.", "content": "The chest roentgenographic findings in Takayasu's arteritis include widening of the ascending aorta, contour irregularities of the descending aorta, arotic calcifications, pulmonary arterial changes, rib notching, and hilar lymphadenopathy. The single most important diagnostic sign is a segmental calcification outlining a localized or diffuse narrowing of the aorta. The other signs may be suspicious or suggestive, but the diagnostic accuracy increases when several findings are present simultaneously.", "contents": "Chest roentgenography as a window to the diagnosis of Takayasu's arteritis. The chest roentgenographic findings in Takayasu's arteritis include widening of the ascending aorta, contour irregularities of the descending aorta, arotic calcifications, pulmonary arterial changes, rib notching, and hilar lymphadenopathy. The single most important diagnostic sign is a segmental calcification outlining a localized or diffuse narrowing of the aorta. The other signs may be suspicious or suggestive, but the diagnostic accuracy increases when several findings are present simultaneously."}
{"id": "PMID:2024", "title": "Evaluation of the Nissen antireflux procedure by esophageal manometry and twenty-four hour pH monitoring.", "content": "Fifteen normal volunteers without symptoms of gastroesophageal reflux and sixteen patients with symptoms of gastroesophageal reflux unresponsive to medical management and having endoscopic esophagitis had esophageal manometry and twenty-four hour pH monitoring of the distal esophagus. The symptomatic patients underwent a Nissen antireflux procedure and were restudied at four months. After surgery, patients had less reflux, a higher sphincteric pressure, and an equal amount of sphincter within the abdomen as did asymptomatic control subjects.", "contents": "Evaluation of the Nissen antireflux procedure by esophageal manometry and twenty-four hour pH monitoring. Fifteen normal volunteers without symptoms of gastroesophageal reflux and sixteen patients with symptoms of gastroesophageal reflux unresponsive to medical management and having endoscopic esophagitis had esophageal manometry and twenty-four hour pH monitoring of the distal esophagus. The symptomatic patients underwent a Nissen antireflux procedure and were restudied at four months. After surgery, patients had less reflux, a higher sphincteric pressure, and an equal amount of sphincter within the abdomen as did asymptomatic control subjects."}
{"id": "PMID:2027", "title": "[Plasma renin activity and plasma aldosterone during anaesthesia and operative stress and beta-adrenergic blockade (author's transl)].", "content": "In 21 patients undergoing ear operations associated with minimal bleeding plasma renin activity and plasma aldosterone concentration were studied before and during surgical procedure, and in the postoperative state. Studies were performed in two groups, one without (n=9) and one with beta-adrenergic blockade by Practolol (n=12). Plasma renin activity increased significantly during halothane anaesthesia alone whereas the surgical manipulations did not further influence mean values significantly. Thus, it seems to be established that anaesthesia per se influences renin secretion. On the other hand Practolol does not show an inhibiting effect. The plasma renin increase following anaesthesia is due to the hemodynamic including renal hemodynamic, changes as well as to activation of the sympatho-adrenal system. Changes in plasma aldosterone are variable. For the greater part of patients with beta-adrenergic blockade an increase during the operative procedure was found. However, in some patients especially in the control group, plasma aldosterone was unchanged or decreased in spite of increasing renin values. Significantly lower plasma potassium concentration in these cases seems to indicate the important contributing role of potassium for the short-term regulation of aldosterone secretion. Plasma sodium concentration remained unchanged for the periods studied.", "contents": "[Plasma renin activity and plasma aldosterone during anaesthesia and operative stress and beta-adrenergic blockade (author's transl)]. In 21 patients undergoing ear operations associated with minimal bleeding plasma renin activity and plasma aldosterone concentration were studied before and during surgical procedure, and in the postoperative state. Studies were performed in two groups, one without (n=9) and one with beta-adrenergic blockade by Practolol (n=12). Plasma renin activity increased significantly during halothane anaesthesia alone whereas the surgical manipulations did not further influence mean values significantly. Thus, it seems to be established that anaesthesia per se influences renin secretion. On the other hand Practolol does not show an inhibiting effect. The plasma renin increase following anaesthesia is due to the hemodynamic including renal hemodynamic, changes as well as to activation of the sympatho-adrenal system. Changes in plasma aldosterone are variable. For the greater part of patients with beta-adrenergic blockade an increase during the operative procedure was found. However, in some patients especially in the control group, plasma aldosterone was unchanged or decreased in spite of increasing renin values. Significantly lower plasma potassium concentration in these cases seems to indicate the important contributing role of potassium for the short-term regulation of aldosterone secretion. Plasma sodium concentration remained unchanged for the periods studied."}
{"id": "PMID:2036", "title": "[Surgical criteria for reoperation in abdominal surgery].", "content": "Analysis of the surgical criteria for reintervention in Abdominal Surgery led to the accentuation of a certain number of pictures of occlusion, general infectious syndromes, postoperative peritonitis, gastro-intestinal fistula and hemorrhagic syndrome. In all cases, the clinical examination can be misleading in particular in the case of peritonitis, and the history and non-surgical criteria must be strongly borne in mind.", "contents": "[Surgical criteria for reoperation in abdominal surgery]. Analysis of the surgical criteria for reintervention in Abdominal Surgery led to the accentuation of a certain number of pictures of occlusion, general infectious syndromes, postoperative peritonitis, gastro-intestinal fistula and hemorrhagic syndrome. In all cases, the clinical examination can be misleading in particular in the case of peritonitis, and the history and non-surgical criteria must be strongly borne in mind."}
{"id": "PMID:2037", "title": "[Nephrologic criteria for reoperation (in the framework of abdominal surgery)].", "content": "38 cases of abdominal surgery in acute renal failure, checked anatomically by reintervention or autopsy, were analyzed. The authors emphasize the frequency of the state of shock (2/3 of the cases) and the misleading nature of local signs. They stress the value of routinely checking creatinine clearance in the preoperative check-up in order to screen for latent renal failure.", "contents": "[Nephrologic criteria for reoperation (in the framework of abdominal surgery)]. 38 cases of abdominal surgery in acute renal failure, checked anatomically by reintervention or autopsy, were analyzed. The authors emphasize the frequency of the state of shock (2/3 of the cases) and the misleading nature of local signs. They stress the value of routinely checking creatinine clearance in the preoperative check-up in order to screen for latent renal failure."}
{"id": "PMID:2038", "title": "[Criteria for reoperation in abdominal surgery (exclusive of surgical and nephrological criteria)].", "content": "In summary, 40 p. 100 of 104 reinterventions carried out in 71 patients from the Resuscitation sector were decided upon in the absence of surgical and nephrological criteria. The authors emphasize the value of the infectious syndrome (74 p. 100 of the cases), of water and electrolyte disorders (60 p. 100 of the cases), and of hypercatabolism (83 p. 100 of the cases).", "contents": "[Criteria for reoperation in abdominal surgery (exclusive of surgical and nephrological criteria)]. In summary, 40 p. 100 of 104 reinterventions carried out in 71 patients from the Resuscitation sector were decided upon in the absence of surgical and nephrological criteria. The authors emphasize the value of the infectious syndrome (74 p. 100 of the cases), of water and electrolyte disorders (60 p. 100 of the cases), and of hypercatabolism (83 p. 100 of the cases)."}
{"id": "PMID:2040", "title": "[Preparation of the patient for reoperation].", "content": "The preparation of patients for reintervention should aim at the correction of: - states of shock and collapse, found in one out of three patients; - hydroelectrolytic disturbances (sodium depletion, hypochloremia, dyskaliemia); - and finally, re-establishment of the acid-base balance.", "contents": "[Preparation of the patient for reoperation]. The preparation of patients for reintervention should aim at the correction of: - states of shock and collapse, found in one out of three patients; - hydroelectrolytic disturbances (sodium depletion, hypochloremia, dyskaliemia); - and finally, re-establishment of the acid-base balance."}
{"id": "PMID:2041", "title": "[Anesthesia in reoperations in abdominal surgery].", "content": "Fifty one patients from different surgical units, hence anesthetized by different anaesthesists, underwent reinterventions in abdominal surgery. The indications for the first intervention essentially involved the supra-mesocolic region of the abdomen (62 out of 100 cases). The operative risk during the first intervention was on the average 18 pour cent. The protocol of the first anaesthesia which was known in 42 cases, was of the narco-ataralgestic type. The date of the return to the operation table varied from 1 to 60 days. The state of the patients was in general catastrophic (organic renal failure, acute respiratory failure). Here again the anaesthesia was of the narco-ataralgesic type but the choice of drugs varied depending on the patients' state. However non significant difference was noted in the average hourly drug consumption between the two interventions. Apart from one circulatory arrest during induction, in one patient with hemorrhagic shock, no death was attributable to the anesthetic technique. The authors, using these findings, attempt to pick out a practical line of behaviour.", "contents": "[Anesthesia in reoperations in abdominal surgery]. Fifty one patients from different surgical units, hence anesthetized by different anaesthesists, underwent reinterventions in abdominal surgery. The indications for the first intervention essentially involved the supra-mesocolic region of the abdomen (62 out of 100 cases). The operative risk during the first intervention was on the average 18 pour cent. The protocol of the first anaesthesia which was known in 42 cases, was of the narco-ataralgestic type. The date of the return to the operation table varied from 1 to 60 days. The state of the patients was in general catastrophic (organic renal failure, acute respiratory failure). Here again the anaesthesia was of the narco-ataralgesic type but the choice of drugs varied depending on the patients' state. However non significant difference was noted in the average hourly drug consumption between the two interventions. Apart from one circulatory arrest during induction, in one patient with hemorrhagic shock, no death was attributable to the anesthetic technique. The authors, using these findings, attempt to pick out a practical line of behaviour."}
{"id": "PMID:2042", "title": "[Peroperative resuscitation in abdominal reoperations].", "content": "Resuscitation of these patients during operation is the only the logical continuation of their preparation. The authors therefore take up the preceding points while emphasizing: - checking vascular filling, by central venous pressure and hourly diuresis; - the necessity for a supply of carbohydrates, which is even more indispensable when the subjects were submitted to parenteral hyperalimentation previously; - the advantages of performing arterial blood gases in order to check artificial ventilation.", "contents": "[Peroperative resuscitation in abdominal reoperations]. Resuscitation of these patients during operation is the only the logical continuation of their preparation. The authors therefore take up the preceding points while emphasizing: - checking vascular filling, by central venous pressure and hourly diuresis; - the necessity for a supply of carbohydrates, which is even more indispensable when the subjects were submitted to parenteral hyperalimentation previously; - the advantages of performing arterial blood gases in order to check artificial ventilation."}
{"id": "PMID:2043", "title": "[The surgical period].", "content": "Reinterventions demand adaptation of the anaesthesia to each particular case. Abdominal exploration and peritoneal toilet are the preliminaries of the surgical act. Continuous confrontation of anesthetic problems with surgical difficulties guarantee effective surgery.", "contents": "[The surgical period]. Reinterventions demand adaptation of the anaesthesia to each particular case. Abdominal exploration and peritoneal toilet are the preliminaries of the surgical act. Continuous confrontation of anesthetic problems with surgical difficulties guarantee effective surgery."}
{"id": "PMID:2044", "title": "[Respiratory problems following repeated abdominal surgery].", "content": "The authors analyzed a series of 100 patients who had undergone a total of 143 reinterventions and found respiratory manifestations in 86 cases. They emphasized the frequency of functional respiratory failure and studied the course of different clinical, radiological and laboratory parameters. The second part is concerned with the physiopathological mechanisms, recalling the main causes of postoperative hypoxemia. Finally the therapeutic chapter is centered on the chronology and modalities of artificial ventilation.", "contents": "[Respiratory problems following repeated abdominal surgery]. The authors analyzed a series of 100 patients who had undergone a total of 143 reinterventions and found respiratory manifestations in 86 cases. They emphasized the frequency of functional respiratory failure and studied the course of different clinical, radiological and laboratory parameters. The second part is concerned with the physiopathological mechanisms, recalling the main causes of postoperative hypoxemia. Finally the therapeutic chapter is centered on the chronology and modalities of artificial ventilation."}
{"id": "PMID:2045", "title": "[Infectious problems in reoperations in abdominal surgery. Apropos of 104 operations].", "content": "Analysis of the problems with infection in a series of 104 reinterventions, enables one to accentuate the importance of infestation from intraperitoneal foci (70 p. 100 of the cases). Extra-peritoneal entry pathways are difficult to prove. Septicemia is found in one out of every three cases. In certain cases, preventive treatment of the extra-peritoneal entry pathways must be opposed to the effectiveness of the surgical act in the eradication of septic foci.", "contents": "[Infectious problems in reoperations in abdominal surgery. Apropos of 104 operations]. Analysis of the problems with infection in a series of 104 reinterventions, enables one to accentuate the importance of infestation from intraperitoneal foci (70 p. 100 of the cases). Extra-peritoneal entry pathways are difficult to prove. Septicemia is found in one out of every three cases. In certain cases, preventive treatment of the extra-peritoneal entry pathways must be opposed to the effectiveness of the surgical act in the eradication of septic foci."}
{"id": "PMID:2046", "title": "[Nutrition in the surgical patient with complications].", "content": "Parenteral feeding in complicated abdominal surgery has been a definite therapeutic progress. However the authors emphasize the divergent attitudes concerning the amounts of nitrogen which should be supplied as well as the variations in the calories-nitrogen ratio. They propose a practical attitude which must be reevaluated individually.", "contents": "[Nutrition in the surgical patient with complications]. Parenteral feeding in complicated abdominal surgery has been a definite therapeutic progress. However the authors emphasize the divergent attitudes concerning the amounts of nitrogen which should be supplied as well as the variations in the calories-nitrogen ratio. They propose a practical attitude which must be reevaluated individually."}
{"id": "PMID:2047", "title": "[Surgical problems. (Apropos of reoperations in abdominal surgery)].", "content": "Out of 1,500 laparotomies carried out between january 1970 and december 1973, 49 patients, i.e. 3.2 p. 100 underwent 61 reinterventions: one out of three patients died. Almost 60 p. 100 of these patients who had undergone operations had essentially parietal complications. The authors analyze the different syndromes which had led to the reintervention while making a special place for parietal problems.", "contents": "[Surgical problems. (Apropos of reoperations in abdominal surgery)]. Out of 1,500 laparotomies carried out between january 1970 and december 1973, 49 patients, i.e. 3.2 p. 100 underwent 61 reinterventions: one out of three patients died. Almost 60 p. 100 of these patients who had undergone operations had essentially parietal complications. The authors analyze the different syndromes which had led to the reintervention while making a special place for parietal problems."}
{"id": "PMID:2048", "title": "[Prognostic factors in reoperations in abdominal surgery. Apropos of 104 operations].", "content": "Analysis of the prognostic factors in abdominal surgical reinterventions accentuates the disparaging character of age, associated defects and emergency. Intercurrent respiratory complications, as well as infectious and renal complications make the prognosis considerably worse.", "contents": "[Prognostic factors in reoperations in abdominal surgery. Apropos of 104 operations]. Analysis of the prognostic factors in abdominal surgical reinterventions accentuates the disparaging character of age, associated defects and emergency. Intercurrent respiratory complications, as well as infectious and renal complications make the prognosis considerably worse."}
{"id": "PMID:2049", "title": "[Respiratory signs of surgical complications after abdominal operations].", "content": "The authors present 29 cases of post-operative respiratory complications in abdominal surgery in subjects without any past history of respiratory disorders. They stress the diagnostic value of these cases of acute respiratory failure shown in a third of the cases of surgical complications.", "contents": "[Respiratory signs of surgical complications after abdominal operations]. The authors present 29 cases of post-operative respiratory complications in abdominal surgery in subjects without any past history of respiratory disorders. They stress the diagnostic value of these cases of acute respiratory failure shown in a third of the cases of surgical complications."}
{"id": "PMID:2050", "title": "[Medico-surgical evaluation of 71 reoperations in abdominal surgery].", "content": "The authors thoroughly checked 71 reinterventions in abdominal surgery. They again found the importance of the factor of infection, respiratory, complications and oligoanuria. The overall percentage of deaths was 58 p. 100, age and associated defects made the prognosis worse.", "contents": "[Medico-surgical evaluation of 71 reoperations in abdominal surgery]. The authors thoroughly checked 71 reinterventions in abdominal surgery. They again found the importance of the factor of infection, respiratory, complications and oligoanuria. The overall percentage of deaths was 58 p. 100, age and associated defects made the prognosis worse."}
{"id": "PMID:2051", "title": "[Postoperative peritonitis. Use of metabolic disorders as criteria for reoperations].", "content": "The authors compared three groups of subjects: - the first group (11 patients) : re-operated for post-operative peritonitis; - the second group (6 patients) : re-operated for evisceration without any underlying lesion; - the third group (8 patients) : non-reoperated, complicated abdominal surgery. Study of the different laboratory parameters helped to identify a number of changes which could plead in favor of reintervention, in the group of peritonitis. Among these modifications, the progressive fall in the urinary Na/K ratio and the negativity of the nitrogen balance appear to play a privileged role.", "contents": "[Postoperative peritonitis. Use of metabolic disorders as criteria for reoperations]. The authors compared three groups of subjects: - the first group (11 patients) : re-operated for post-operative peritonitis; - the second group (6 patients) : re-operated for evisceration without any underlying lesion; - the third group (8 patients) : non-reoperated, complicated abdominal surgery. Study of the different laboratory parameters helped to identify a number of changes which could plead in favor of reintervention, in the group of peritonitis. Among these modifications, the progressive fall in the urinary Na/K ratio and the negativity of the nitrogen balance appear to play a privileged role."}
{"id": "PMID:2052", "title": "[Our experience with reoperations in abdominal surgery. (54 reoperations in 46 patients in the last 4 years)].", "content": "The authors analyze 54 reinterventions in abdominal surgery in 46 patients, and present the lesions found on reintervention. In one out of two cases there is an intra-peritoneal septic focus. In more than 25 p. 100 of the cases the lesions were multiple. They oppose the localized septic foci and the occlusions which are of good prognosis, with the diffuse septic foci, acute pancreatitis and fistulae whose course is more often than not fatal.", "contents": "[Our experience with reoperations in abdominal surgery. (54 reoperations in 46 patients in the last 4 years)]. The authors analyze 54 reinterventions in abdominal surgery in 46 patients, and present the lesions found on reintervention. In one out of two cases there is an intra-peritoneal septic focus. In more than 25 p. 100 of the cases the lesions were multiple. They oppose the localized septic foci and the occlusions which are of good prognosis, with the diffuse septic foci, acute pancreatitis and fistulae whose course is more often than not fatal."}
{"id": "PMID:2056", "title": "[Demythification of acupunctural anesthesia].", "content": "The so-called method of acupuncture anesthesia uses a series of techniques: selection of patients, psychotherapy, premedication, adjuvants (morphinomimetics, local anesthetics), choice of points (very varied) whose specificity has not been demonstrated, mechanical or electrical stimulation (with very differents depending on the \"schools\". The effects of these procedures are inconstant. They are slowly established. At best, they are manifested by a hypo-esthesia which is more or less wide-spread and is not accompanied by any \"anti-reflex\" protection. The action of the organism's different functions is not known in detail. There are no statistical studies in the strict sense of the term, in man. It can be roughly estimated that out of 100 surgical patients chosen, about 30 undergo the intervention in acceptable conditions in the western world. The cases, although nothing is concealed in Hano\u00ef as well as in Peking, are difficult, and should only be handled by experienced anesthetists-resuscitators, with knowledge of acupuncture. Certain of the method's advantages only appear in comparison with bad \"chemical\" anesthesia (atoxicity, simplicity, economy), others are practically investions (anallergic effects, anti-infections, anti-shock) or at least abuse of language. The disadvantages apart from the inconstancy of effectiveness, the absence of \"protection\", the duration of induction, consist of lack of standardization of techniques, difficulties of animal experiments and the lack of rational explanation of the mechanism of action.", "contents": "[Demythification of acupunctural anesthesia]. The so-called method of acupuncture anesthesia uses a series of techniques: selection of patients, psychotherapy, premedication, adjuvants (morphinomimetics, local anesthetics), choice of points (very varied) whose specificity has not been demonstrated, mechanical or electrical stimulation (with very differents depending on the \"schools\". The effects of these procedures are inconstant. They are slowly established. At best, they are manifested by a hypo-esthesia which is more or less wide-spread and is not accompanied by any \"anti-reflex\" protection. The action of the organism's different functions is not known in detail. There are no statistical studies in the strict sense of the term, in man. It can be roughly estimated that out of 100 surgical patients chosen, about 30 undergo the intervention in acceptable conditions in the western world. The cases, although nothing is concealed in Hano\u00ef as well as in Peking, are difficult, and should only be handled by experienced anesthetists-resuscitators, with knowledge of acupuncture. Certain of the method's advantages only appear in comparison with bad \"chemical\" anesthesia (atoxicity, simplicity, economy), others are practically investions (anallergic effects, anti-infections, anti-shock) or at least abuse of language. The disadvantages apart from the inconstancy of effectiveness, the absence of \"protection\", the duration of induction, consist of lack of standardization of techniques, difficulties of animal experiments and the lack of rational explanation of the mechanism of action."}
{"id": "PMID:2057", "title": "[Study of the effects of Alfatesin on cerebral blood flow in cats].", "content": "The cerebral haemodynamic effects of CT 1341 also called Alfatesin, an anaesthetic steroid, were studied in the cat by means of the Xenon 133 isotopic clearance method to measure the cerebral blood flow. The injection or intravenous drip of Alfatesin in animals whose arterio PCO2 was kept unchanged induced a cerebral blood flow diminution, the importance of which was proportional to the injected dose. The cerebral blood flow fall was partly due to a cerebral arterio vasoconstriction evidenced by direct observation of the cortex vessels and by a diminution of the intracranial presure. During a deep anaesthesia induced by Alfatesin with recurrent burst suppression, there was a loss of cerebral blood flow autoregulation while the CO2 cerebral vascular reactivity was maintained. This last result accounts for the increase in cerebral blood flow parallel to the hypercapnia that could be observed among animals breathing freely.", "contents": "[Study of the effects of Alfatesin on cerebral blood flow in cats]. The cerebral haemodynamic effects of CT 1341 also called Alfatesin, an anaesthetic steroid, were studied in the cat by means of the Xenon 133 isotopic clearance method to measure the cerebral blood flow. The injection or intravenous drip of Alfatesin in animals whose arterio PCO2 was kept unchanged induced a cerebral blood flow diminution, the importance of which was proportional to the injected dose. The cerebral blood flow fall was partly due to a cerebral arterio vasoconstriction evidenced by direct observation of the cortex vessels and by a diminution of the intracranial presure. During a deep anaesthesia induced by Alfatesin with recurrent burst suppression, there was a loss of cerebral blood flow autoregulation while the CO2 cerebral vascular reactivity was maintained. This last result accounts for the increase in cerebral blood flow parallel to the hypercapnia that could be observed among animals breathing freely."}
{"id": "PMID:2058", "title": "[Effects of Alfatesin on total cerebral blood flow in humans].", "content": "The total cerebral blood flow was measured by the Xe 133 in 9 patients, before and during a pure Alfatesine induced anaesthesia. With a perfusion flow of 0,04 ml/kg/mn, the total flow underwent a mean fall of 38 p. 100 that was linked neither to any systemic pressure variations nor to variations of the PaCO2. This fall was linked to a cerebral arterio vasoconstriction as it was evidenced by arteriographic images.", "contents": "[Effects of Alfatesin on total cerebral blood flow in humans]. The total cerebral blood flow was measured by the Xe 133 in 9 patients, before and during a pure Alfatesine induced anaesthesia. With a perfusion flow of 0,04 ml/kg/mn, the total flow underwent a mean fall of 38 p. 100 that was linked neither to any systemic pressure variations nor to variations of the PaCO2. This fall was linked to a cerebral arterio vasoconstriction as it was evidenced by arteriographic images."}
{"id": "PMID:2059", "title": "[Study of pressor drops during continuous peridural analgesia in gerontologic surgery].", "content": "A statistical study bearing upon othe fall of blood pressure concomitant with the setting of peridural anaesthesia was carried out upon an homogeneous series of patients over 75 belonging to groups III and IV of the A S A classification for interventions seating below the IXth metamere. From this study, it seems to follow that: - for starting maximum arterial tensions over 180 mm/Hg, pressure falls are virtually constant in absolute value; - the most important variations in pressure falls are to be found in abdominal surgery; - the lowest figure in blood pressure which accompanies the achievement of surgical analgesia takes place about the 24 th minute whatever the type of surgery can be; - no significant link can be evidence between the importance of the fall in blood pressure and the consumption of the mixture required for surgical analgesia.", "contents": "[Study of pressor drops during continuous peridural analgesia in gerontologic surgery]. A statistical study bearing upon othe fall of blood pressure concomitant with the setting of peridural anaesthesia was carried out upon an homogeneous series of patients over 75 belonging to groups III and IV of the A S A classification for interventions seating below the IXth metamere. From this study, it seems to follow that: - for starting maximum arterial tensions over 180 mm/Hg, pressure falls are virtually constant in absolute value; - the most important variations in pressure falls are to be found in abdominal surgery; - the lowest figure in blood pressure which accompanies the achievement of surgical analgesia takes place about the 24 th minute whatever the type of surgery can be; - no significant link can be evidence between the importance of the fall in blood pressure and the consumption of the mixture required for surgical analgesia."}
{"id": "PMID:2060", "title": "[Harzard of chronic exposure to halothane for operating room personnel].", "content": "This study shows that the staff working in an operating room is repeatedly being exposed to appreciable doses of halothane vapours. A continuous measurement of the concentrations in the ambient air gave results ranging from 5 to 30 ppm. Summits from 50 to 70 ppm were noted. The inhaling of halothane was evidenced by the presence of brominated metabolites in the urine of the staff. A mean 14,59 mg/l was found with women anaesthesists. Therefore it is quite possible that the halothane spread in the air should be held responsible for the discomfort felt in particular by anaesthesists. To prevent this risk of chronic intoxication by those vapours, there ought to be a device permitting either to evacuate them outside or to collect them while regenerating the polluted air through an active carbon filter if one has not got at one's disposal an airing system offering over 20 renewals of fresh air per hour. The fitting up of a permanent control device equipped with warning light and bell is also justified.", "contents": "[Harzard of chronic exposure to halothane for operating room personnel]. This study shows that the staff working in an operating room is repeatedly being exposed to appreciable doses of halothane vapours. A continuous measurement of the concentrations in the ambient air gave results ranging from 5 to 30 ppm. Summits from 50 to 70 ppm were noted. The inhaling of halothane was evidenced by the presence of brominated metabolites in the urine of the staff. A mean 14,59 mg/l was found with women anaesthesists. Therefore it is quite possible that the halothane spread in the air should be held responsible for the discomfort felt in particular by anaesthesists. To prevent this risk of chronic intoxication by those vapours, there ought to be a device permitting either to evacuate them outside or to collect them while regenerating the polluted air through an active carbon filter if one has not got at one's disposal an airing system offering over 20 renewals of fresh air per hour. The fitting up of a permanent control device equipped with warning light and bell is also justified."}
{"id": "PMID:2061", "title": "[Organization of first aid on the northern motorway in Picardy. Role of the regional Medical First Aid Unit].", "content": "The Picardy regional S.A.M.U. implanted in Amiens, has participated in the implantation of antennae of the S.M.U.R. whereby aid can be given accident cases on the northern motorway. After a brief historical review of the creation of these antennae, and presentation of what exists in the sections of the northern motorway not in Picardy, the means of the regional S.A.M.U. are presented, and the way it which it functions, with regards to specific problems concerning medical aid on the motorway. The results of the S.M.U.R. activities are presented and discussed. The necessity for good coordination of medical aid, the fundamental role of the regional S.A.M.U., is particularly emphasized.", "contents": "[Organization of first aid on the northern motorway in Picardy. Role of the regional Medical First Aid Unit]. The Picardy regional S.A.M.U. implanted in Amiens, has participated in the implantation of antennae of the S.M.U.R. whereby aid can be given accident cases on the northern motorway. After a brief historical review of the creation of these antennae, and presentation of what exists in the sections of the northern motorway not in Picardy, the means of the regional S.A.M.U. are presented, and the way it which it functions, with regards to specific problems concerning medical aid on the motorway. The results of the S.M.U.R. activities are presented and discussed. The necessity for good coordination of medical aid, the fundamental role of the regional S.A.M.U., is particularly emphasized."}
{"id": "PMID:2062", "title": "[Helicopters and medical first aid units. Role of Medical First Aid Unit 94].", "content": "For the transport of injured and sick patients, the helicopter (even the mono-turbine type) offers greater advantages when compared to land vehicles: - more comfort (less vibrations, accelerations and decelerations); - a greater speed, that is to say a 61 p. 100 gain of time upon the distance and a gain from 29 up to 44 p. 100 upon the total amount of time taken up by each transport. This gain in time enables valuable specialised medical teams to be more available: - more precise time-tables than by land which namely makes it easier to receive the patients. The drawbacks are linked with the risks which are not nonexistent but rather less serious than by land. The drawbacks also depend upon the weather-conditions (although this factor does not matter much in our area), upon nuisances such as the noise (which is more important but far more transitory than by ambulance) and chiefly upon the cost of air-transport. In fact, the mean cost of a medical land transport amounts roughly to one thousand Francs, a quarter of which only does represent the actual cost of medical aid. For a similar transport, the helicopter comes to a 47 mns flight. There are several ways of making good use of a helicopter. Practical problems have been solved. The \"SAMU 94\" experience goes back to 1973 and includes over 500 transports by helicopter essentially with the help of the teams and the helicopters belonging to the Paris Base (Civil Protection and the Fire-Brigade). For flights over urban areas, it is to be desired in the future that only twin-turbine helicopters should be used.", "contents": "[Helicopters and medical first aid units. Role of Medical First Aid Unit 94]. For the transport of injured and sick patients, the helicopter (even the mono-turbine type) offers greater advantages when compared to land vehicles: - more comfort (less vibrations, accelerations and decelerations); - a greater speed, that is to say a 61 p. 100 gain of time upon the distance and a gain from 29 up to 44 p. 100 upon the total amount of time taken up by each transport. This gain in time enables valuable specialised medical teams to be more available: - more precise time-tables than by land which namely makes it easier to receive the patients. The drawbacks are linked with the risks which are not nonexistent but rather less serious than by land. The drawbacks also depend upon the weather-conditions (although this factor does not matter much in our area), upon nuisances such as the noise (which is more important but far more transitory than by ambulance) and chiefly upon the cost of air-transport. In fact, the mean cost of a medical land transport amounts roughly to one thousand Francs, a quarter of which only does represent the actual cost of medical aid. For a similar transport, the helicopter comes to a 47 mns flight. There are several ways of making good use of a helicopter. Practical problems have been solved. The \"SAMU 94\" experience goes back to 1973 and includes over 500 transports by helicopter essentially with the help of the teams and the helicopters belonging to the Paris Base (Civil Protection and the Fire-Brigade). For flights over urban areas, it is to be desired in the future that only twin-turbine helicopters should be used."}
{"id": "PMID:2063", "title": "[Clinical and therapeutic problems posed by hangings. Apropos of 67 cases].", "content": "Starting from a collection of 67 cases of hanging taken over by the Anesthesia Resuscitation Department belonging to Reims Hospital University Centre, the authors report their clinical observations and make an analytical confrontation of this type of accident according to various criteria such as: - the initial physical condition of the victims; - the evolution of the symptoms; - the various medical treatments used. The immediate consequences of miscarried hangings lead to a physio-pathological argument dealing mainly with the neurological and breathing manifestations. The elements of this argument enable the writers to back up certain therapeutic orientations among which hyperbaric oxygen therapy and early prescription of which seems to be wished for in the most severe forms of hanging.", "contents": "[Clinical and therapeutic problems posed by hangings. Apropos of 67 cases]. Starting from a collection of 67 cases of hanging taken over by the Anesthesia Resuscitation Department belonging to Reims Hospital University Centre, the authors report their clinical observations and make an analytical confrontation of this type of accident according to various criteria such as: - the initial physical condition of the victims; - the evolution of the symptoms; - the various medical treatments used. The immediate consequences of miscarried hangings lead to a physio-pathological argument dealing mainly with the neurological and breathing manifestations. The elements of this argument enable the writers to back up certain therapeutic orientations among which hyperbaric oxygen therapy and early prescription of which seems to be wished for in the most severe forms of hanging."}
{"id": "PMID:2064", "title": "[Severe complications of subclavian vein catheterization].", "content": "The authors report 4 observations of severe involvement induced by sub-clavian catheterization: - 2 catheter-embolisms; - 1 venous thrombosis and one hydrothoraxx. One embolism and the hydrothorax were caused by a faulty puncturing. The thrombosis was the result of a relative stenosis of the vein induced by a loop of the catheter in the Pirogoff confluent. Next, the authors develop the facts given by the literature bearing upon each one of these complications.", "contents": "[Severe complications of subclavian vein catheterization]. The authors report 4 observations of severe involvement induced by sub-clavian catheterization: - 2 catheter-embolisms; - 1 venous thrombosis and one hydrothoraxx. One embolism and the hydrothorax were caused by a faulty puncturing. The thrombosis was the result of a relative stenosis of the vein induced by a loop of the catheter in the Pirogoff confluent. Next, the authors develop the facts given by the literature bearing upon each one of these complications."}
{"id": "PMID:2065", "title": "[Acute renal insufficiency and fat embolism].", "content": "The authors report ten cases of renal insufficiency observed among a series of 43 cases of fat embolism. It is a matter of eraly oligoanuria (starting beween the 2nd and the 4th day). Its severity depends on the lesions involved : prolonged cardio-vascular collapse - cranio-encephalic lesion. The renal insufficiency does not seem typical of fat embolism. It must be essentially linked to a cardio-vascular collapse and/or to a disseminated intra-vascular coagulation.", "contents": "[Acute renal insufficiency and fat embolism]. The authors report ten cases of renal insufficiency observed among a series of 43 cases of fat embolism. It is a matter of eraly oligoanuria (starting beween the 2nd and the 4th day). Its severity depends on the lesions involved : prolonged cardio-vascular collapse - cranio-encephalic lesion. The renal insufficiency does not seem typical of fat embolism. It must be essentially linked to a cardio-vascular collapse and/or to a disseminated intra-vascular coagulation."}
{"id": "PMID:2067", "title": "[Effects of nasogastric intubation on respiratory resistance and work in newborn and premature infants].", "content": "The nasal resistance participates for almost 50 p. 100 in the resistance of airways (RVA) of the new-borns whose respiration is mainly nasal. The possibility of an oral respiration in case of partial or total occlusion of nasal way is almost null. In order to determinate the effects of a naso-gastric suction of the RVA 10 normal infants (3 prematures, 7 new-born babies) were studied by plethysmographia. The presence of the suction brought a systematic and significant increase of RVA (the coefficient of transformation = 1,318 +/- 0,21 p is less than 0,001). In the nine infants for whom the resistant work (WR) was estimated is increased proportionaly to the increase of RVA (deltaRVA) (coef. of transformation = 1,44 +/- 0,44, p is less than 0,001). However the proportional increase of WR is not systematic superior for 3 prematures and 1 new-born baby and similar in one case. These variations can be explained by various adjustments of the V. The increase of work imposed by the presence of a naso-gastric suction cannot be underestimated in particular for the prematures.", "contents": "[Effects of nasogastric intubation on respiratory resistance and work in newborn and premature infants]. The nasal resistance participates for almost 50 p. 100 in the resistance of airways (RVA) of the new-borns whose respiration is mainly nasal. The possibility of an oral respiration in case of partial or total occlusion of nasal way is almost null. In order to determinate the effects of a naso-gastric suction of the RVA 10 normal infants (3 prematures, 7 new-born babies) were studied by plethysmographia. The presence of the suction brought a systematic and significant increase of RVA (the coefficient of transformation = 1,318 +/- 0,21 p is less than 0,001). In the nine infants for whom the resistant work (WR) was estimated is increased proportionaly to the increase of RVA (deltaRVA) (coef. of transformation = 1,44 +/- 0,44, p is less than 0,001). However the proportional increase of WR is not systematic superior for 3 prematures and 1 new-born baby and similar in one case. These variations can be explained by various adjustments of the V. The increase of work imposed by the presence of a naso-gastric suction cannot be underestimated in particular for the prematures."}
{"id": "PMID:2068", "title": "[Treatment of severe forms of idiopathic respiratory distress in newborn infants using constant negative perithoracic pressure].", "content": "49 children with a severe idiopathic respiratory distress syndrome were treated by continuous negative pressure ranging from 5 cm of water to a negative pressure of 13 cm of water around the thorax. The partial pressure of oxygen rose significantly in the majority of cases, and the alveolo-arterial gradient also significantly diminished by more than 100 mm of mercury. 29 children were treated by this method alone, but in 20 other children owing to the failure of constant negative pressure, respiratory assistance either by intermittent pressure ventilation or intermittent positive pressure ventilation was associated. On the whole 35 out of 49 children survived. The complications which were met with are analyzed. Continuous negative pressure seems to be a safe and effective method for improving oxygenation in the idiopathic respiratory distress syndrome.", "contents": "[Treatment of severe forms of idiopathic respiratory distress in newborn infants using constant negative perithoracic pressure]. 49 children with a severe idiopathic respiratory distress syndrome were treated by continuous negative pressure ranging from 5 cm of water to a negative pressure of 13 cm of water around the thorax. The partial pressure of oxygen rose significantly in the majority of cases, and the alveolo-arterial gradient also significantly diminished by more than 100 mm of mercury. 29 children were treated by this method alone, but in 20 other children owing to the failure of constant negative pressure, respiratory assistance either by intermittent pressure ventilation or intermittent positive pressure ventilation was associated. On the whole 35 out of 49 children survived. The complications which were met with are analyzed. Continuous negative pressure seems to be a safe and effective method for improving oxygenation in the idiopathic respiratory distress syndrome."}
{"id": "PMID:2069", "title": "[PAH clearance measurement without urine samples in the newborn infant with respiratory distress].", "content": "PAH clearance was carried out in 12 newborns, hospitalized in the infantile resuscitation unit for respiratory distress. 6 of these children weighed less than 2.5 kg, 4 had hyaline membrane disease, 6 had either amniotic abnormalities or transitory tachypnea, 2 were surgical patients: one right diaphragmatic hernia, one post-operative respiratory complication after intervention for neonatal occlusion. In 9 cases the newborn was under controled artificial ventilation associated with PEEP at 5 to 7 cm of water. In all of the cases, the hemodynamic, metabolic and blood gas conditions were normal. A control series of 11 newnorn was carried out in a pediatric unit, the clearance was done without urine samples, the rough value of the figures found varied from 5.5 ml per minute to 30 ml per minute in the respiratory distress series and 16 to 62 ml per minute in the control series. The analysis of these results in rendered difficult by the juxtaposition of several factors: Choice of a reference criterion: body surface area, PAH space, patient's weight theoretical weight of the kidneys. The factor of prematurity. The problem of the date of the investigation in comparison with the date of birth.", "contents": "[PAH clearance measurement without urine samples in the newborn infant with respiratory distress]. PAH clearance was carried out in 12 newborns, hospitalized in the infantile resuscitation unit for respiratory distress. 6 of these children weighed less than 2.5 kg, 4 had hyaline membrane disease, 6 had either amniotic abnormalities or transitory tachypnea, 2 were surgical patients: one right diaphragmatic hernia, one post-operative respiratory complication after intervention for neonatal occlusion. In 9 cases the newborn was under controled artificial ventilation associated with PEEP at 5 to 7 cm of water. In all of the cases, the hemodynamic, metabolic and blood gas conditions were normal. A control series of 11 newnorn was carried out in a pediatric unit, the clearance was done without urine samples, the rough value of the figures found varied from 5.5 ml per minute to 30 ml per minute in the respiratory distress series and 16 to 62 ml per minute in the control series. The analysis of these results in rendered difficult by the juxtaposition of several factors: Choice of a reference criterion: body surface area, PAH space, patient's weight theoretical weight of the kidneys. The factor of prematurity. The problem of the date of the investigation in comparison with the date of birth."}
{"id": "PMID:2070", "title": "[Transport of \"high-risk\" newborn infants. (Apropos of 159 emergency calls by the SAMU 94-Service d'Aide M\u00e9dicale Urgente-Emergency Health Service)].", "content": "Analysis of our experience confirms in the domain of the newborn the fundamental notion of the Emergency medical call. The EMC has two objectives: 1--Emergency treatment before the patient is moved, and the correction of failing vital functions by a medical team skilled in problems of neonates. 2--Transportation of the neonate in a stable condition, to the Intensive Care unit. The quality of such transportation depends closely upon the quality of the medical care given and upon organisation. It can only be carried out in the context of a system coordinated by a \"coordinating physician\" (e.g. SAMU 94). This coordinating physician has responsibility for logistics, telephone coordination, and application of the call procedure as rapidly as possible. From a logistical point of view, only coordination between:--SAMU-SMUR;--Medical team of the Intensive care unit;--Requesting service make possible the provision and quality of continuous supplies of oxygen, warmth, sugar - all under aseptic conditions, indispensable to the quality of survival of the neonate. In addition, we feel it essential--that the delay before the call is answered be as brief as possible;--that the call should be dealt with by a mixed team, including at least one physician experienced in neonatal problems;--that the choice of vehicle used for transportation should be better adapted to the situation. This choice is the responsibility of the coordinating physician, who should base his decisions on two fundamental requirements:--rapidity of dealing with the call;--personal safety of those involved. This without losing sight of--Prevention of perinatal problems lies part with the detection of high risk pregnancies, with the aim of arranging delivery in specialised \"mother and baby\" centres where close collaboration between obstetrician and paediatrician is assured.--The development of transportation of the \"high-risk\" neonate, which is so costly in manpower and equipment, depends closely upon general concepts of health care in France, which should be aimed at:--the prevention of prematury;--the detection of high risk pregnancies;--the development of mother and baby centres.", "contents": "[Transport of \"high-risk\" newborn infants. (Apropos of 159 emergency calls by the SAMU 94-Service d'Aide M\u00e9dicale Urgente-Emergency Health Service)]. Analysis of our experience confirms in the domain of the newborn the fundamental notion of the Emergency medical call. The EMC has two objectives: 1--Emergency treatment before the patient is moved, and the correction of failing vital functions by a medical team skilled in problems of neonates. 2--Transportation of the neonate in a stable condition, to the Intensive Care unit. The quality of such transportation depends closely upon the quality of the medical care given and upon organisation. It can only be carried out in the context of a system coordinated by a \"coordinating physician\" (e.g. SAMU 94). This coordinating physician has responsibility for logistics, telephone coordination, and application of the call procedure as rapidly as possible. From a logistical point of view, only coordination between:--SAMU-SMUR;--Medical team of the Intensive care unit;--Requesting service make possible the provision and quality of continuous supplies of oxygen, warmth, sugar - all under aseptic conditions, indispensable to the quality of survival of the neonate. In addition, we feel it essential--that the delay before the call is answered be as brief as possible;--that the call should be dealt with by a mixed team, including at least one physician experienced in neonatal problems;--that the choice of vehicle used for transportation should be better adapted to the situation. This choice is the responsibility of the coordinating physician, who should base his decisions on two fundamental requirements:--rapidity of dealing with the call;--personal safety of those involved. This without losing sight of--Prevention of perinatal problems lies part with the detection of high risk pregnancies, with the aim of arranging delivery in specialised \"mother and baby\" centres where close collaboration between obstetrician and paediatrician is assured.--The development of transportation of the \"high-risk\" neonate, which is so costly in manpower and equipment, depends closely upon general concepts of health care in France, which should be aimed at:--the prevention of prematury;--the detection of high risk pregnancies;--the development of mother and baby centres."}
{"id": "PMID:2071", "title": "[Transport of newborn infants. Apropos of 114 cases].", "content": "The transport of 114 newborn less than 24 hours old carried out in 1972 and 1973 by the Paris SAMU (Professor M. CARA'S Unit) is studied. (he delay of arrival of the medical team is on the average one hour, the child arrives in the Resuscitation center approximately two and a quarter hours after the call. In 15 cases an umbilical catheter was put in place; in 27 cases the child was intubated, artificial ventilation  was carried out during transport. On arrival, from the mean values, the temperature was 25.2 degrees, the pH 7.28, the pO2 112, the blood sugar 1.53 g.Three practical conclusions must be drawn: reserve high risk deliveries for specialized centers, when the degree of emergency compells delivery in a badly equipped center, contact the SAMU from the beginning of labour, render the actions carried out by the transporting doctor even more rigorous and controled, which implies an organized SMUR which is well equipped and trained.", "contents": "[Transport of newborn infants. Apropos of 114 cases]. The transport of 114 newborn less than 24 hours old carried out in 1972 and 1973 by the Paris SAMU (Professor M. CARA'S Unit) is studied. (he delay of arrival of the medical team is on the average one hour, the child arrives in the Resuscitation center approximately two and a quarter hours after the call. In 15 cases an umbilical catheter was put in place; in 27 cases the child was intubated, artificial ventilation  was carried out during transport. On arrival, from the mean values, the temperature was 25.2 degrees, the pH 7.28, the pO2 112, the blood sugar 1.53 g.Three practical conclusions must be drawn: reserve high risk deliveries for specialized centers, when the degree of emergency compells delivery in a badly equipped center, contact the SAMU from the beginning of labour, render the actions carried out by the transporting doctor even more rigorous and controled, which implies an organized SMUR which is well equipped and trained."}
{"id": "PMID:2072", "title": "[Vascular and infectious enteropathy in newborn infants. Reflections on pathogeny; clinical and therapeutic deductions. Apropos of 45 cases].", "content": "Necrotizing enterocolitis of the new-born has an anatomical definition: lesions discovered during surgery or on post-mortem examination. Progress in neanatal shock reveals facts already known in the adult and in experimental medicine: concept of preferential and circulatory by-pass. A considerable decrease in blood flow is seen in the latter during shock; this shock is sometimes not important. Mesenteric circulation is the best example. This syndrome should therefore be included in the major vascular changes of neonatal period. Vascular and infectious enteropathy is a broader term which seems more appropriate because of aetiological and therapeutic implications. The aetiology should be considered as a sum of several factors varying from one patient to another (multifactorial disease). The circulatory component remains very important. Its severity depends on whether or not it is treated. Four notions should be defined: -- Census of population of subjects with \"high risk\" of vascular and infectious enteropathy (score trial); -- Isolation of clinical pictures corresponding to a medical or surgical stage; Grouping of elements for immediate and long term prognosis; -- Grouping of elements for immediate and long term prognosis; -- Proposal of preventive treatment to the \"high risk\" patients (surgery; continuons parenteral and enteral feeding are intientionally left out in this paper). The interest of this concept of the disease is to eradicate severe forms as in the neonatal idiopathic respiratory distress syndrome where a similar concept was adopted.", "contents": "[Vascular and infectious enteropathy in newborn infants. Reflections on pathogeny; clinical and therapeutic deductions. Apropos of 45 cases]. Necrotizing enterocolitis of the new-born has an anatomical definition: lesions discovered during surgery or on post-mortem examination. Progress in neanatal shock reveals facts already known in the adult and in experimental medicine: concept of preferential and circulatory by-pass. A considerable decrease in blood flow is seen in the latter during shock; this shock is sometimes not important. Mesenteric circulation is the best example. This syndrome should therefore be included in the major vascular changes of neonatal period. Vascular and infectious enteropathy is a broader term which seems more appropriate because of aetiological and therapeutic implications. The aetiology should be considered as a sum of several factors varying from one patient to another (multifactorial disease). The circulatory component remains very important. Its severity depends on whether or not it is treated. Four notions should be defined: -- Census of population of subjects with \"high risk\" of vascular and infectious enteropathy (score trial); -- Isolation of clinical pictures corresponding to a medical or surgical stage; Grouping of elements for immediate and long term prognosis; -- Grouping of elements for immediate and long term prognosis; -- Proposal of preventive treatment to the \"high risk\" patients (surgery; continuons parenteral and enteral feeding are intientionally left out in this paper). The interest of this concept of the disease is to eradicate severe forms as in the neonatal idiopathic respiratory distress syndrome where a similar concept was adopted."}
{"id": "PMID:2073", "title": "[Pre-, per-, and postoperative resuscitation in thoracic surgery in newborn infants].", "content": "The authors report their five year-experience in reanimation during thoracic surgery in the new-born. The report concerns 66 cases (43 atresias of the oesophagus and 23 diaphragmatic hernias). Prognosonis depends on: 1 -- A permanent temam of suitably qualified doctors ready to carry out at any time the required therapy on the infant. 2 -- Free air way (kinesitherapy, continous and prolonged suction of oesophageal atresias and bronchial suction). 3 -- Ventilation (surgery on clean lungs in atresias, diaphragmatic prosthesis and suturing of skin in hernias). Respect of these rules in diaphragmatic hernias saved 12 lives out of 23; in oesophageal atresias, 16 survived out of 16 cases classified as good cases, and the total survival rate was 73%.", "contents": "[Pre-, per-, and postoperative resuscitation in thoracic surgery in newborn infants]. The authors report their five year-experience in reanimation during thoracic surgery in the new-born. The report concerns 66 cases (43 atresias of the oesophagus and 23 diaphragmatic hernias). Prognosonis depends on: 1 -- A permanent temam of suitably qualified doctors ready to carry out at any time the required therapy on the infant. 2 -- Free air way (kinesitherapy, continous and prolonged suction of oesophageal atresias and bronchial suction). 3 -- Ventilation (surgery on clean lungs in atresias, diaphragmatic prosthesis and suturing of skin in hernias). Respect of these rules in diaphragmatic hernias saved 12 lives out of 23; in oesophageal atresias, 16 survived out of 16 cases classified as good cases, and the total survival rate was 73%."}
{"id": "PMID:2074", "title": "[Congenital cardiopathies appearing during the neonatal period. The view points of the cardiologist, the hemodynamics specialist, the surgeon, and the anesthetist].", "content": "The best chances of survival for a new-born depend on the following factors: the possibility of clinical and haemodynamic diagnosis of the malformation, adequate reanimation and surgery. All this must be carried out as early as possible. Although catheterization is very risky it should be complete and as fast as possible, under monitoring of ventilation and haemodynamies. Reanimation is very important before, during and after surgery; it should be more preventive than curative. Very often, surgery is only palliative at this age. Taking into account progress in surgical techniques, the authors report their experience in anaesthesia and ressuscitation of 100 patients under 10 days old. They were all operated on in Laennec in Professor MATHEY's department but only some of them were catheterized there.", "contents": "[Congenital cardiopathies appearing during the neonatal period. The view points of the cardiologist, the hemodynamics specialist, the surgeon, and the anesthetist]. The best chances of survival for a new-born depend on the following factors: the possibility of clinical and haemodynamic diagnosis of the malformation, adequate reanimation and surgery. All this must be carried out as early as possible. Although catheterization is very risky it should be complete and as fast as possible, under monitoring of ventilation and haemodynamies. Reanimation is very important before, during and after surgery; it should be more preventive than curative. Very often, surgery is only palliative at this age. Taking into account progress in surgical techniques, the authors report their experience in anaesthesia and ressuscitation of 100 patients under 10 days old. They were all operated on in Laennec in Professor MATHEY's department but only some of them were catheterized there."}
{"id": "PMID:2075", "title": "[Leukomalacia and subsequent brain status in relation to intensive neonatal care].", "content": "Leucomalacia or white matter necrosis is one of the major aspects of neonatal encephalopathies, especially in the premature baby. These necroses are found mainly in the deep periventricular white matter of the \"semi-oval centre\". Characteristically, they are ischaemic and their anatomical and histological progress is rapid: coagulation necrosis with rapid axonal fragmentation followed by polymorphic cellular reaction with glial cells and macrophages. Regeneration in the minor forms consists of glyosis process in severe forms; multiple cavities appear in a few weeks. Physiopathogenic hypotheses put forward are related to: 1 -- the very anatomic aite: special tissue and terminal arteries, 2 -- onset of myelinization process, 3 -- associated clinical and biological lesions such as hypoxia, acidosis and hypotention. These lesions are symptom-free during the neonatal period. One of us suggested in 1962 that these could be the anatomical basis of spastic monoplegia or diplegia (LITTLE's disease). All motor cerebral sequelae have disappeared since 10 years. This is particularly significant mainly in the case of spastic diplegia of the former premature baby under 2500 g. This decrease coincides with improvement in neonatal care, especially correction of hypoxia, acidosis and cardiovascular collapse. These findings seem to support the pathogenic hypotheses.", "contents": "[Leukomalacia and subsequent brain status in relation to intensive neonatal care]. Leucomalacia or white matter necrosis is one of the major aspects of neonatal encephalopathies, especially in the premature baby. These necroses are found mainly in the deep periventricular white matter of the \"semi-oval centre\". Characteristically, they are ischaemic and their anatomical and histological progress is rapid: coagulation necrosis with rapid axonal fragmentation followed by polymorphic cellular reaction with glial cells and macrophages. Regeneration in the minor forms consists of glyosis process in severe forms; multiple cavities appear in a few weeks. Physiopathogenic hypotheses put forward are related to: 1 -- the very anatomic aite: special tissue and terminal arteries, 2 -- onset of myelinization process, 3 -- associated clinical and biological lesions such as hypoxia, acidosis and hypotention. These lesions are symptom-free during the neonatal period. One of us suggested in 1962 that these could be the anatomical basis of spastic monoplegia or diplegia (LITTLE's disease). All motor cerebral sequelae have disappeared since 10 years. This is particularly significant mainly in the case of spastic diplegia of the former premature baby under 2500 g. This decrease coincides with improvement in neonatal care, especially correction of hypoxia, acidosis and cardiovascular collapse. These findings seem to support the pathogenic hypotheses."}
{"id": "PMID:2076", "title": "[Neonatal listeriosis (based on 43 cases)].", "content": "Using results in 43 cases from two neonatal units (Paris-Tours), the authors emphasize the essential facts concerning neonatal listeriosis. 1 -- Incidence: -- of an infectious maternal disease (32 cases out of 43), -- of permaturity (60% of cases), -- and of foetal distress (72%). 2 -- Clinical study: Early neonatal infectious are the only forms seen; clinical signs appear before the first day (40 out of 42). These is septicaemia with mainly respiratory signs (olypnoea, laboured breathing). Their presence and clinical history should incite to take swabs of the orifices and carry out blood culture. The new-born are given double antibiotherapy (penicline and aninoside or kanamycine and gentalline) while waiting for laboratory reports. This routine treatment based on maternal past history and on mild clinical signs at this stage has improved the prognosis of these septicaemias (16 deaths out of 43 children).", "contents": "[Neonatal listeriosis (based on 43 cases)]. Using results in 43 cases from two neonatal units (Paris-Tours), the authors emphasize the essential facts concerning neonatal listeriosis. 1 -- Incidence: -- of an infectious maternal disease (32 cases out of 43), -- of permaturity (60% of cases), -- and of foetal distress (72%). 2 -- Clinical study: Early neonatal infectious are the only forms seen; clinical signs appear before the first day (40 out of 42). These is septicaemia with mainly respiratory signs (olypnoea, laboured breathing). Their presence and clinical history should incite to take swabs of the orifices and carry out blood culture. The new-born are given double antibiotherapy (penicline and aninoside or kanamycine and gentalline) while waiting for laboratory reports. This routine treatment based on maternal past history and on mild clinical signs at this stage has improved the prognosis of these septicaemias (16 deaths out of 43 children)."}
{"id": "PMID:2077", "title": "[Appearance of coagulation disorders in the non-healthy newborn infant].", "content": "Coagulation abnormalities are particularly frequent in neonatal pathology and justify exploration of hemostasis in the newborn. First of all we established a profile of coagulation in the newborn using our own results and data from the literature. Contrasting with a deficit in numerous factors (II - VII - IX - X - XI - and XII), overall coagulation is normal, or even increased. The fibrinolytic system is characterized by a low plasminogen level but the activity of this system is transitorily increased. Then we recall the known syndromes: avitaminosis K, constitutional deficits in the coagulation factors, isolated thrombopenia, disseminated intravascular clotting. However numerous problems persist. Abnormalities in the clotting factors are frequently difficult to interpret. Correlation between the clinical and laboratory pictures does not always exist. We emphasize the necessity for preventive measures.", "contents": "[Appearance of coagulation disorders in the non-healthy newborn infant]. Coagulation abnormalities are particularly frequent in neonatal pathology and justify exploration of hemostasis in the newborn. First of all we established a profile of coagulation in the newborn using our own results and data from the literature. Contrasting with a deficit in numerous factors (II - VII - IX - X - XI - and XII), overall coagulation is normal, or even increased. The fibrinolytic system is characterized by a low plasminogen level but the activity of this system is transitorily increased. Then we recall the known syndromes: avitaminosis K, constitutional deficits in the coagulation factors, isolated thrombopenia, disseminated intravascular clotting. However numerous problems persist. Abnormalities in the clotting factors are frequently difficult to interpret. Correlation between the clinical and laboratory pictures does not always exist. We emphasize the necessity for preventive measures."}
{"id": "PMID:2078", "title": "[Perinatal assistance in the delivery room--reanimation of the newborn infant].", "content": "In most cases birth brings an infant who can rapidly adapt himself to a normal extra-uterine life. However, sometimes and most of all, in \"high risk\" cases, this infant needs a correct surveillance before and after the delivery in order to prevent morbidity and especially perinatal morbidity. Our actual knowledge, derived from the fantastic progress of Perinatalogy, demonstrates that, in order to assure the wanted end of the pregnancy, the only assistance of the delivery at hospital by a qualified obstetrician is not enough. It is necessary to have a continuous surveillance at the beginning of the pregnancy and during the pregnancy and a correct attention at the mother - foetus binomial during the labor and the delivery. That will permit the discovery of pre- para and post-natal factors, to undertake the prevention and to lower the number of perinatal mortality.", "contents": "[Perinatal assistance in the delivery room--reanimation of the newborn infant]. In most cases birth brings an infant who can rapidly adapt himself to a normal extra-uterine life. However, sometimes and most of all, in \"high risk\" cases, this infant needs a correct surveillance before and after the delivery in order to prevent morbidity and especially perinatal morbidity. Our actual knowledge, derived from the fantastic progress of Perinatalogy, demonstrates that, in order to assure the wanted end of the pregnancy, the only assistance of the delivery at hospital by a qualified obstetrician is not enough. It is necessary to have a continuous surveillance at the beginning of the pregnancy and during the pregnancy and a correct attention at the mother - foetus binomial during the labor and the delivery. That will permit the discovery of pre- para and post-natal factors, to undertake the prevention and to lower the number of perinatal mortality."}
{"id": "PMID:2079", "title": "[Therapeutic trials in pregnant women].", "content": "The increasing use of medications during pregnancy and labour leads to the question of their true effectiveness and the absence of harmful effects, for both mother and foetus. Study of the action of medications given to the pregnant woman requires clinical trials with precise methodology including, as an essential stage, the definition of an experimental protocol. Random distribution of the subjects to the various groups and statistical analysis of the results based upon objective criteria are essential. No study of the action of a medication as far as mother and foetus should be undertaken without prior parmacological and pharmacokinetic trials.", "contents": "[Therapeutic trials in pregnant women]. The increasing use of medications during pregnancy and labour leads to the question of their true effectiveness and the absence of harmful effects, for both mother and foetus. Study of the action of medications given to the pregnant woman requires clinical trials with precise methodology including, as an essential stage, the definition of an experimental protocol. Random distribution of the subjects to the various groups and statistical analysis of the results based upon objective criteria are essential. No study of the action of a medication as far as mother and foetus should be undertaken without prior parmacological and pharmacokinetic trials."}
{"id": "PMID:2080", "title": "[Drug interference and the role of anesthesia in such interference].", "content": "This report considers interference between medications for, on the one hand, drugs given during pregnancy, and, on the other hand, drugs given to the pregnant women and anaesthetic agents. Consideration is given to progestational agents, oxytocics, beta-mimetics, corticosteroids, insulin, hypotensive agents, diuretics and psychiatric drugs. For each case of interference, an attempt is made to provide practical data, with particular respect to those combinations frequently prescribed by obstetricians, e.g. the combination of the beta-mimetics and corticosteroids with the aim of preventing impending premature onset of labour and to ensure foetal pulmonary maturation; the combination of insulin and corticosteroids given to diabetics with the aim of preventing hyaline membrane disease; the combination of corticosteroids with anti-histamines in the treatment of rhesus disease; the association of oxytocics with large quantities of intravenous fluid in the case of post-partum haemorrhage and hypontensive medication combinations and the problems which may result with emergency anaesthesis.", "contents": "[Drug interference and the role of anesthesia in such interference]. This report considers interference between medications for, on the one hand, drugs given during pregnancy, and, on the other hand, drugs given to the pregnant women and anaesthetic agents. Consideration is given to progestational agents, oxytocics, beta-mimetics, corticosteroids, insulin, hypotensive agents, diuretics and psychiatric drugs. For each case of interference, an attempt is made to provide practical data, with particular respect to those combinations frequently prescribed by obstetricians, e.g. the combination of the beta-mimetics and corticosteroids with the aim of preventing impending premature onset of labour and to ensure foetal pulmonary maturation; the combination of insulin and corticosteroids given to diabetics with the aim of preventing hyaline membrane disease; the combination of corticosteroids with anti-histamines in the treatment of rhesus disease; the association of oxytocics with large quantities of intravenous fluid in the case of post-partum haemorrhage and hypontensive medication combinations and the problems which may result with emergency anaesthesis."}
{"id": "PMID:2081", "title": "[Drug heritage of the newborn infant].", "content": "The medicamental heritage of the new-born baby is a reality that we are more and more realizing. During intra-uterine life, the foetus is placed under different maternal influences that the new-born baby is done an \"old\" and unsafe one who can present, as early as his birth, modifications of his own metabolism. To know if this heritage is really a dotation or an empoisoned gift, is an important question that we are going to study in light of experimental data and constatations of clinical pharmacology.", "contents": "[Drug heritage of the newborn infant]. The medicamental heritage of the new-born baby is a reality that we are more and more realizing. During intra-uterine life, the foetus is placed under different maternal influences that the new-born baby is done an \"old\" and unsafe one who can present, as early as his birth, modifications of his own metabolism. To know if this heritage is really a dotation or an empoisoned gift, is an important question that we are going to study in light of experimental data and constatations of clinical pharmacology."}
{"id": "PMID:2082", "title": "[Influence on the fetus of drugs taken during pregnancy].", "content": "The use of drugs during pregnancy is very common; some substances can provoke in the foetus troubles and anatomical or functional disorders which may be detected either at birth or later on. Then it is necessary the physicians restrict the prescription of therapeutical agents for and only for well-knowned indications. The education of people in regard of this subject is also necessary about drugs used during pregnancy without medical advices.", "contents": "[Influence on the fetus of drugs taken during pregnancy]. The use of drugs during pregnancy is very common; some substances can provoke in the foetus troubles and anatomical or functional disorders which may be detected either at birth or later on. Then it is necessary the physicians restrict the prescription of therapeutical agents for and only for well-knowned indications. The education of people in regard of this subject is also necessary about drugs used during pregnancy without medical advices."}
{"id": "PMID:2083", "title": "[Evaluation of fetal maturity at birth].", "content": "It is very important to evaluate the degree of maturity of a new-born infant in order: - to appreciate the chronological age when the date of the last period is unknown or doubtful, - to compare the degree of maturation with the weight and size of the infant, in regard of estimating the intra-uterine growth and detecting early a lateness or advance of this growth.", "contents": "[Evaluation of fetal maturity at birth]. It is very important to evaluate the degree of maturity of a new-born infant in order: - to appreciate the chronological age when the date of the last period is unknown or doubtful, - to compare the degree of maturation with the weight and size of the infant, in regard of estimating the intra-uterine growth and detecting early a lateness or advance of this growth."}
{"id": "PMID:2084", "title": "[Severe respiratory distress with stubborn hypoxemia in newborn infants whose mothers had had placenta previa].", "content": "The study of 16 newborn of birthweight less than or equal to 2,200 g characterized by a common point: the presence of PLACENTA PRAEVIA IN THE MOTHER, enabled us to come to grips with the severe respiratory distress that these newborn can have. From the clinical standpoint: there is always early respiratory distress. From the radiological standpoint: by far the most dominant pathology was interstitial edema, giving rise to a WET LUNG. From the biochemical standpoint: the blood gases were characterized in a certain number of cases by hypoxemia which was refractory to the usual forms of treatment. From the mechanical standpoint: measurements carried out in 4 patients confirmed the extraordinary fall in these patients' compliance. The clinical, radiological, blood gas and mechanical analysis enabled one to differenciate 2 main types of indications for artificial ventilation: -- acute hypoxemia, -- the idea of an increased need for oxygen. In these 2 types of indications for artificial ventilation, it was apparent that the treatment of choice is constant positive pressure which may or may not be combined with intermittent positive pressure. With this treatment technique, none of the patients progressed to massive atelectasis. It can be said that with the advent of techniques of ventilation by high pressure combining IPP with CPP, one has definitively eliminated from this pathological picture, the principal cause of death: --anoxia due to massive alveolar collapse.", "contents": "[Severe respiratory distress with stubborn hypoxemia in newborn infants whose mothers had had placenta previa]. The study of 16 newborn of birthweight less than or equal to 2,200 g characterized by a common point: the presence of PLACENTA PRAEVIA IN THE MOTHER, enabled us to come to grips with the severe respiratory distress that these newborn can have. From the clinical standpoint: there is always early respiratory distress. From the radiological standpoint: by far the most dominant pathology was interstitial edema, giving rise to a WET LUNG. From the biochemical standpoint: the blood gases were characterized in a certain number of cases by hypoxemia which was refractory to the usual forms of treatment. From the mechanical standpoint: measurements carried out in 4 patients confirmed the extraordinary fall in these patients' compliance. The clinical, radiological, blood gas and mechanical analysis enabled one to differenciate 2 main types of indications for artificial ventilation: -- acute hypoxemia, -- the idea of an increased need for oxygen. In these 2 types of indications for artificial ventilation, it was apparent that the treatment of choice is constant positive pressure which may or may not be combined with intermittent positive pressure. With this treatment technique, none of the patients progressed to massive atelectasis. It can be said that with the advent of techniques of ventilation by high pressure combining IPP with CPP, one has definitively eliminated from this pathological picture, the principal cause of death: --anoxia due to massive alveolar collapse."}
{"id": "PMID:2085", "title": "[Primary management of labor using neuroleptic analgesia].", "content": "Within the limits granted, neuroleptanalgesia constitutes a very interesting technique in the major part of management of labour. In particular it has the advantage of preserving maternal consciousness. On the other hand, it allows analgesia of rather long duration, which renders early management of labour possible while still respecting its physiology. The institution of this technique demands the presence at the parturients bedside, not only of the obstetrician and the medwife but also that of a qualified anesthetist. As in all cases of major management of labour it engages the responsability of the obstetrical team which undertakes it and this is even more so, the earlier it is started. To us its indications seem comparable with those of Gamma OH: the early management of labour however has the advantage over the latter of preserving maternal consciouness. Moreover it proved to be particularly interesting in the management of breech presentations. But if its properties are an advantage in the indications which we have just mentioned, they can constitute an invonvenience and restrain its use under different circumstances: its slowness of induction, the absence of narcosis which limits the effect on cervical resistance means that one prefers the Toulouse method using pentothal for the management of labour after 7 centimeters of dilatation. In conclusion, it seems important to us to state that neuroleptanalgesia is not the ideal method for management of labour any more than is thiopental or Gamma-OH. Other techniques merit being studied. Their study must obey strict rules in order to specify the risks and therefore the indications and limits. It should cover different fields which are, pharmacology, the objective assessment, by quantitative criteria, of the effects on uterine contraction, on the mother's clinical and biological state as well as that of the fetus in utero, then that of the child in the first hours of live and up to the first years of his development.", "contents": "[Primary management of labor using neuroleptic analgesia]. Within the limits granted, neuroleptanalgesia constitutes a very interesting technique in the major part of management of labour. In particular it has the advantage of preserving maternal consciousness. On the other hand, it allows analgesia of rather long duration, which renders early management of labour possible while still respecting its physiology. The institution of this technique demands the presence at the parturients bedside, not only of the obstetrician and the medwife but also that of a qualified anesthetist. As in all cases of major management of labour it engages the responsability of the obstetrical team which undertakes it and this is even more so, the earlier it is started. To us its indications seem comparable with those of Gamma OH: the early management of labour however has the advantage over the latter of preserving maternal consciouness. Moreover it proved to be particularly interesting in the management of breech presentations. But if its properties are an advantage in the indications which we have just mentioned, they can constitute an invonvenience and restrain its use under different circumstances: its slowness of induction, the absence of narcosis which limits the effect on cervical resistance means that one prefers the Toulouse method using pentothal for the management of labour after 7 centimeters of dilatation. In conclusion, it seems important to us to state that neuroleptanalgesia is not the ideal method for management of labour any more than is thiopental or Gamma-OH. Other techniques merit being studied. Their study must obey strict rules in order to specify the risks and therefore the indications and limits. It should cover different fields which are, pharmacology, the objective assessment, by quantitative criteria, of the effects on uterine contraction, on the mother's clinical and biological state as well as that of the fetus in utero, then that of the child in the first hours of live and up to the first years of his development."}
{"id": "PMID:2086", "title": "[Drugs most frequently used during pregnancy and labor and their effects].", "content": "It is rather difficult to draw up a list of the drugs most frequently used during pregnancy, and to specify their action on the mother, the uterus ans the fetus bearing in mind the differences between them. This difficulty results in particular from the high number of drugs owing to: the frequency of prescriptions and selfmedication in the pregnant woman who suffers from numerous disorders, and the possibility of a pathology associated with the pregnancy or a pathology due to the pregnancy itself thereby defining the \"high risk\" pregnancy. On this background already modified by pregnancy, under the hold of numerous drugs, an anesthetic can be necessary in addition during labour or delivery, the frequency of which can be estimated as being approximately 20 per cent. It is not possible to study all therapeutic agents in a single communication. One can only evoke the influence of the most currently used drugs; analgesics, antibiotics, diuretics, sleeping tablets, anti-hypertensives and those aimed at the neuropsychiatric system (anti-depression agents, neuroleptics, tranquillizers) which are so frequently used at present. Finally, during labour the number of parturients who receive no drugs is rare: ocytocic and anti-spasmodic agents can also interfere with an anesthetic. All of these ideas which are more and more difficult to acquire are important to know. In fact the person in charge of the delivery must prescribe as little drugs as possible (in order to avoid multiple drug interference which is rather difficult to predict) knowing the possible action of drugs on the fetus (in order to allow best adaptation to life in our atmosphere after delivery) and foreseeing the possible necessity for an anesthetic. In his turn, the anesthetist should have a good knowledge of obstetrical physiology and pathology and the drugs capable of being used during pregnancy and labour in order to be able to choose the best adapted anesthetic. This emphasized the importance of a well integrated obstetrico-anesthetic team in which each member knows the problems of the other, with the aim of being the least possible noxious for the mother, and the future newborn, the fetus. This also emphasizes the necessity for anesthetists attached to the ostetrical unit, knowing like the obstetrician the histories of those women with \"high risk\" pregnancies. Obstetrical anesthetics cannot be improvised.", "contents": "[Drugs most frequently used during pregnancy and labor and their effects]. It is rather difficult to draw up a list of the drugs most frequently used during pregnancy, and to specify their action on the mother, the uterus ans the fetus bearing in mind the differences between them. This difficulty results in particular from the high number of drugs owing to: the frequency of prescriptions and selfmedication in the pregnant woman who suffers from numerous disorders, and the possibility of a pathology associated with the pregnancy or a pathology due to the pregnancy itself thereby defining the \"high risk\" pregnancy. On this background already modified by pregnancy, under the hold of numerous drugs, an anesthetic can be necessary in addition during labour or delivery, the frequency of which can be estimated as being approximately 20 per cent. It is not possible to study all therapeutic agents in a single communication. One can only evoke the influence of the most currently used drugs; analgesics, antibiotics, diuretics, sleeping tablets, anti-hypertensives and those aimed at the neuropsychiatric system (anti-depression agents, neuroleptics, tranquillizers) which are so frequently used at present. Finally, during labour the number of parturients who receive no drugs is rare: ocytocic and anti-spasmodic agents can also interfere with an anesthetic. All of these ideas which are more and more difficult to acquire are important to know. In fact the person in charge of the delivery must prescribe as little drugs as possible (in order to avoid multiple drug interference which is rather difficult to predict) knowing the possible action of drugs on the fetus (in order to allow best adaptation to life in our atmosphere after delivery) and foreseeing the possible necessity for an anesthetic. In his turn, the anesthetist should have a good knowledge of obstetrical physiology and pathology and the drugs capable of being used during pregnancy and labour in order to be able to choose the best adapted anesthetic. This emphasized the importance of a well integrated obstetrico-anesthetic team in which each member knows the problems of the other, with the aim of being the least possible noxious for the mother, and the future newborn, the fetus. This also emphasizes the necessity for anesthetists attached to the ostetrical unit, knowing like the obstetrician the histories of those women with \"high risk\" pregnancies. Obstetrical anesthetics cannot be improvised."}
{"id": "PMID:2087", "title": "[Important physiological considerations in artificial respiration and reanimation of newborn infants].", "content": "The methods used for ventilation of the neonate shold be based upon consideration of the physiological changes which occure in the lungs and circulation at birth of the normal infant. Three important changes must be taken into consideration. The first is the formation of a residual volume of alveolar gas, the second the resorption of pulmonary fluid and the third a decrease in pulmonary vascular resistance, upon which is dependent the change from foetal circulation to that of the neonate. To begin insufflation of foetal lungs it is necessary to use a pressure of between 20 and 30 cm H2O. After the first insufflation, a good deal of air remains in the lungs, even during expiration, as long as pulmonary \"surfactant\" is present. In the absence of the latter, residual pressure at the end of expiration is necessary in order to avoid the lung emptying itself of air. The resorption of pulmonary liquid from the alveolar spaces into the blood is dependent upon a change in the permeability of the alveolar epithelium, which renders possible the rapid passage of water via the channels which open, probably between the epithelial cells, and this change is dependent upon an expansion of the lungs by a pressure of between 35 and 40 cm H2O. Dilatation of the pulmonary vessels depends in part upon an increase in partial pressure of oxygen and a fall in carbon dioxide in the environment of the pulmonary arterioles, and in part upon mechanical changes brought about by the movements of ventilatation.", "contents": "[Important physiological considerations in artificial respiration and reanimation of newborn infants]. The methods used for ventilation of the neonate shold be based upon consideration of the physiological changes which occure in the lungs and circulation at birth of the normal infant. Three important changes must be taken into consideration. The first is the formation of a residual volume of alveolar gas, the second the resorption of pulmonary fluid and the third a decrease in pulmonary vascular resistance, upon which is dependent the change from foetal circulation to that of the neonate. To begin insufflation of foetal lungs it is necessary to use a pressure of between 20 and 30 cm H2O. After the first insufflation, a good deal of air remains in the lungs, even during expiration, as long as pulmonary \"surfactant\" is present. In the absence of the latter, residual pressure at the end of expiration is necessary in order to avoid the lung emptying itself of air. The resorption of pulmonary liquid from the alveolar spaces into the blood is dependent upon a change in the permeability of the alveolar epithelium, which renders possible the rapid passage of water via the channels which open, probably between the epithelial cells, and this change is dependent upon an expansion of the lungs by a pressure of between 35 and 40 cm H2O. Dilatation of the pulmonary vessels depends in part upon an increase in partial pressure of oxygen and a fall in carbon dioxide in the environment of the pulmonary arterioles, and in part upon mechanical changes brought about by the movements of ventilatation."}
{"id": "PMID:2088", "title": "[Spectrofluorometric determination of a new beta-blocking agent, acebutolol in blood and urine].", "content": "The authors describe a simple method of spectrofluorimetric estimation of acebutolol, applicable to blood and urine, sufficiently sensitive to obtain therapeutic concentrations. After administration of a 200 mg dose by mouth, one may observe a maximal plasma concentration 3 hours later, with average values of 1.02 +/- 0.20 mg/liter. The principle of the estimation is based on acid hydrolysis of the product, then condensation of the liberated amine with nitroso-1 naphtol-2 to give a fluorescent derivative (stimulation 460 nm, emission 545 nm).", "contents": "[Spectrofluorometric determination of a new beta-blocking agent, acebutolol in blood and urine]. The authors describe a simple method of spectrofluorimetric estimation of acebutolol, applicable to blood and urine, sufficiently sensitive to obtain therapeutic concentrations. After administration of a 200 mg dose by mouth, one may observe a maximal plasma concentration 3 hours later, with average values of 1.02 +/- 0.20 mg/liter. The principle of the estimation is based on acid hydrolysis of the product, then condensation of the liberated amine with nitroso-1 naphtol-2 to give a fluorescent derivative (stimulation 460 nm, emission 545 nm)."}
{"id": "PMID:2089", "title": "[Determination of the activity of serum ornithine carbamoyltranferase : working conditions in a veronal-acetate medium].", "content": "Ornithine carbamyl transferase activity was determined by estimation of the citrulline formed during the reaction. Citrulline is estimated by diacetylmonoxime in the presence of thiosemicarbazide. The conditions of enzyme analysis were then studied in buffer veronal-acetate medium at 37 degrees C. The optimum pH for activity depended on the ornithine concentration, but was independent of carbamyl-phosphate concentration. At pH 7.8, ornithine at concentrations higher than 1.6 mM inhibited enzyme activity, ornithine Km was 0.208 mM and that of carbamyl-phosphate was 1.92 mM. The incubation time for determination of OCT activity was 15 minutes. Citrulline production was proportional to the enzyme concentration up to activities of 180 units/l. Serum urea was destroyed by a urease of high quality, so that the formation of citrulline in the control reagents was minimal. Reference values, determined on a hospital population, without liver, heart or pulmonary disease, lay between 4.7 +/- 2.3 units/l. The coefficient of variation of the technique, determined on a pool of serum of moderate activity was 8 units/l i.e. 5.1 per cent.", "contents": "[Determination of the activity of serum ornithine carbamoyltranferase : working conditions in a veronal-acetate medium]. Ornithine carbamyl transferase activity was determined by estimation of the citrulline formed during the reaction. Citrulline is estimated by diacetylmonoxime in the presence of thiosemicarbazide. The conditions of enzyme analysis were then studied in buffer veronal-acetate medium at 37 degrees C. The optimum pH for activity depended on the ornithine concentration, but was independent of carbamyl-phosphate concentration. At pH 7.8, ornithine at concentrations higher than 1.6 mM inhibited enzyme activity, ornithine Km was 0.208 mM and that of carbamyl-phosphate was 1.92 mM. The incubation time for determination of OCT activity was 15 minutes. Citrulline production was proportional to the enzyme concentration up to activities of 180 units/l. Serum urea was destroyed by a urease of high quality, so that the formation of citrulline in the control reagents was minimal. Reference values, determined on a hospital population, without liver, heart or pulmonary disease, lay between 4.7 +/- 2.3 units/l. The coefficient of variation of the technique, determined on a pool of serum of moderate activity was 8 units/l i.e. 5.1 per cent."}
{"id": "PMID:2091", "title": "Comparison of anileridine and pethidine in preventing pain responses during nitrous oxide-oxygen anaesthesia.", "content": "The analgesic potency of anileridine and pethidine was compared in 28 patients by measuring their effect on withdrawal movements caused by pinching of the skin or by surgery during N2O + O2 anaesthesia. It appeared that anileridine is 3.5 to 4 times as potent as pethidine on a weight basis. In equianalgesic doses the incidence of side effects was equal after both drugs.", "contents": "Comparison of anileridine and pethidine in preventing pain responses during nitrous oxide-oxygen anaesthesia. The analgesic potency of anileridine and pethidine was compared in 28 patients by measuring their effect on withdrawal movements caused by pinching of the skin or by surgery during N2O + O2 anaesthesia. It appeared that anileridine is 3.5 to 4 times as potent as pethidine on a weight basis. In equianalgesic doses the incidence of side effects was equal after both drugs."}
{"id": "PMID:2092", "title": "Effects of the cardioselective beta-blocker metoprolol in angina pectoris. A subacute study with exercise tests.", "content": "The effects of the cardioselective beta-blocker, metoprolol, were evaluated under double-blind conditions in eighteen patients with angina pectoris. During an introductory run-in period of eight weeks, a placebo was given single-blindly. Thereafter two double-blind crossover periods each of four weeks followed, either 20 mg metroprolol or placebo being given t.i.d. Metoprolol gave a significant reduction in the number of anginal attacks and in nitroglycerin consumption. The patients' subjective assessments of their daily angina pectoris symptoms also showed a significant improvement compared with the placebo. At the end of each period, a standardized exercise test was performed. In comparison with placebo, metoprolol gave a significant increase of total work performed until the appearance of 1 mm ST-segment depression and until the end of exercise. The heart rate was significantly reduced at rest and during exercise. The blood pressure was significantly reduced only during exercise. None of the patients reported any severe unwanted effects. The complaints reported were mild to moderate, and the frequency during metoprolol treatment was even lower than during placebo treatment. No signs or symptoms of cardiac failure were seen in any of these patients on any occasion. It is concluded that 20 mg metoprolol t.i.d. is of benefit in the treatment of angina pectoris but further benefit might be obtained with higher doses.", "contents": "Effects of the cardioselective beta-blocker metoprolol in angina pectoris. A subacute study with exercise tests. The effects of the cardioselective beta-blocker, metoprolol, were evaluated under double-blind conditions in eighteen patients with angina pectoris. During an introductory run-in period of eight weeks, a placebo was given single-blindly. Thereafter two double-blind crossover periods each of four weeks followed, either 20 mg metroprolol or placebo being given t.i.d. Metoprolol gave a significant reduction in the number of anginal attacks and in nitroglycerin consumption. The patients' subjective assessments of their daily angina pectoris symptoms also showed a significant improvement compared with the placebo. At the end of each period, a standardized exercise test was performed. In comparison with placebo, metoprolol gave a significant increase of total work performed until the appearance of 1 mm ST-segment depression and until the end of exercise. The heart rate was significantly reduced at rest and during exercise. The blood pressure was significantly reduced only during exercise. None of the patients reported any severe unwanted effects. The complaints reported were mild to moderate, and the frequency during metoprolol treatment was even lower than during placebo treatment. No signs or symptoms of cardiac failure were seen in any of these patients on any occasion. It is concluded that 20 mg metoprolol t.i.d. is of benefit in the treatment of angina pectoris but further benefit might be obtained with higher doses."}
{"id": "PMID:2094", "title": "[Effect of the phosphorus concentration on novobiocin formation by the producer Act. spheroides].", "content": "According to the literature data biosynthesis of novobiocin by Act. spheroides unlike other antibiotics does not practically depend on the phosphorus levels in the medium. In the present paper it is shown that production of novobiocin in natural media is sensitive to the concentration of mineral phosphorus in the medium. The optimal concentration of phosphorus for biosynthesis of novobiocin is almost within the same ranges as that for biosynthesis of streptomycin, tetracyclines and oleandomycin.", "contents": "[Effect of the phosphorus concentration on novobiocin formation by the producer Act. spheroides]. According to the literature data biosynthesis of novobiocin by Act. spheroides unlike other antibiotics does not practically depend on the phosphorus levels in the medium. In the present paper it is shown that production of novobiocin in natural media is sensitive to the concentration of mineral phosphorus in the medium. The optimal concentration of phosphorus for biosynthesis of novobiocin is almost within the same ranges as that for biosynthesis of streptomycin, tetracyclines and oleandomycin."}
{"id": "PMID:2095", "title": "[Microbiological study of gentamiycin].", "content": "Gentamycin prepared at the All-Union Research Institute of Antibiotics did not differ by its antibacterial spectrum and the activity level from gentamycin samples from other countries. By its activity against clinical strains of Ps. aeruginosa gentamycin was somewhat inferior than polymyxin but much more superior than carbenicillin. An agar-diffusion method using Bac. pumilus NTCC 8241 as the test microbe was developed for determination of gentamycin activity. The gentamycin sulfate complex and the components of gentamycin had the same activity levels, antibacterial spectrum and diffusion capacity.", "contents": "[Microbiological study of gentamiycin]. Gentamycin prepared at the All-Union Research Institute of Antibiotics did not differ by its antibacterial spectrum and the activity level from gentamycin samples from other countries. By its activity against clinical strains of Ps. aeruginosa gentamycin was somewhat inferior than polymyxin but much more superior than carbenicillin. An agar-diffusion method using Bac. pumilus NTCC 8241 as the test microbe was developed for determination of gentamycin activity. The gentamycin sulfate complex and the components of gentamycin had the same activity levels, antibacterial spectrum and diffusion capacity."}
{"id": "PMID:2096", "title": "[Use of lincomycin, methicillin and ristomycin in the nutrient media for isolating pathogenic intestinal microorganisms].", "content": "Elective-differentiating solid nutrient media for simultaneous isolation of Vibrioes, Salmonella and Shigella were developed. Antibiotics active against grampostive microflora and dry bile salts inhibiting the growth of Proteus were used as the inhibitors of the growth of the accompanying microflora. The medium was lincomycin and the bile salts may be prepared in a dry form.", "contents": "[Use of lincomycin, methicillin and ristomycin in the nutrient media for isolating pathogenic intestinal microorganisms]. Elective-differentiating solid nutrient media for simultaneous isolation of Vibrioes, Salmonella and Shigella were developed. Antibiotics active against grampostive microflora and dry bile salts inhibiting the growth of Proteus were used as the inhibitors of the growth of the accompanying microflora. The medium was lincomycin and the bile salts may be prepared in a dry form."}
{"id": "PMID:2097", "title": "[Characteristics of the oxidative metabolism in strains with varying levels of fucidin biosynthesis].", "content": "Oxidative capacity of the fusidin-producing strains with various biosynthetic activity was studied comparatively. The studies showed that by their capacity to oxidize pyruvate and some metabolites of the tricarboxylic acid cycle (acetate, succinate, malate) the strains were arranged in the order reverse to their antibiotic activity. Such regularity was observed during the whole fermentation process and was most pronounced by the 3rd and 4th days (beginning of the idiophase). The rate of glucose oxidation was higher in more active strains. The same regularity was noted in the 2nd phase of the strain development associated with beginning of fusidin biosynthesis. In the 1st phase (the 1st and 2nd days) the strains almost did not differ by their capacity to oxidize glucose. By oxidation of phosphorylated ethers of carbohydrates (glucose-6-phosphate and fructoso-6-phosphate) the strains did not differ. Various fusidin-producing strains oxidized NAD-N and NADP-N approximately with the same rate. It is supposed that mutations leading to increased antibiotic production are associated with changes in acetate metabolism in the direction of more intensive biosynthesis of isoprenoid compounds, potential precursors of the fusidin molecule.", "contents": "[Characteristics of the oxidative metabolism in strains with varying levels of fucidin biosynthesis]. Oxidative capacity of the fusidin-producing strains with various biosynthetic activity was studied comparatively. The studies showed that by their capacity to oxidize pyruvate and some metabolites of the tricarboxylic acid cycle (acetate, succinate, malate) the strains were arranged in the order reverse to their antibiotic activity. Such regularity was observed during the whole fermentation process and was most pronounced by the 3rd and 4th days (beginning of the idiophase). The rate of glucose oxidation was higher in more active strains. The same regularity was noted in the 2nd phase of the strain development associated with beginning of fusidin biosynthesis. In the 1st phase (the 1st and 2nd days) the strains almost did not differ by their capacity to oxidize glucose. By oxidation of phosphorylated ethers of carbohydrates (glucose-6-phosphate and fructoso-6-phosphate) the strains did not differ. Various fusidin-producing strains oxidized NAD-N and NADP-N approximately with the same rate. It is supposed that mutations leading to increased antibiotic production are associated with changes in acetate metabolism in the direction of more intensive biosynthesis of isoprenoid compounds, potential precursors of the fusidin molecule."}
{"id": "PMID:2098", "title": "Lactulose therapy in Shigella carrier state and acute dysentery.", "content": "Antibiotic-resistant shigella are increasingly prevalent. Lactulose, a non-absorbable disaccharide, was investigated as an alternative therapy for shigella infection on the hypothesis that the short-chain fatty acids (inhibitory to shigella) resulting from metabolism of lactulose by normal colonic flora would diminish shigella excretion. A long-term antibiotic-refractory carrier (large bowel) excreting 10(4) to 10(7)Shigella sonnei/g of feces was given two courses of lactulose (of 24 and 16 days duration). During lactulose therapy, excretion of shigella was greatly diminished (24-day course) or suppressed below detectable levels (16-day course), but returned to pretreatment levels upon discontinuation of lactulose. The volunteers who developed induced shigellosis during an efficacy test of oral Shigella flexneri 2a vaccine were randomly given oral ampicillin, lactulose, or placebo in double-blind fashion. Daily rectal cultures were taken. After 4 days of therapy, cultures were still positive in four out of four men on lactulose, three of three on placebo and none of three on ampicillin. Mean stool pH of men receiving lactulose (6.1) was significantly lower than those getting ampicillin (7.4), P < 0.01, or placebo (7.0), P < 0.05. Only in the lactulose group was mean stool pH during therapy significantly decreased compared with the level off therapy (6.1 versus 7.1), P < 0.02. Lactulose shows promise for the treatment of shigella carriers but appears ineffective in treatment of acute shigellosis.", "contents": "Lactulose therapy in Shigella carrier state and acute dysentery. Antibiotic-resistant shigella are increasingly prevalent. Lactulose, a non-absorbable disaccharide, was investigated as an alternative therapy for shigella infection on the hypothesis that the short-chain fatty acids (inhibitory to shigella) resulting from metabolism of lactulose by normal colonic flora would diminish shigella excretion. A long-term antibiotic-refractory carrier (large bowel) excreting 10(4) to 10(7)Shigella sonnei/g of feces was given two courses of lactulose (of 24 and 16 days duration). During lactulose therapy, excretion of shigella was greatly diminished (24-day course) or suppressed below detectable levels (16-day course), but returned to pretreatment levels upon discontinuation of lactulose. The volunteers who developed induced shigellosis during an efficacy test of oral Shigella flexneri 2a vaccine were randomly given oral ampicillin, lactulose, or placebo in double-blind fashion. Daily rectal cultures were taken. After 4 days of therapy, cultures were still positive in four out of four men on lactulose, three of three on placebo and none of three on ampicillin. Mean stool pH of men receiving lactulose (6.1) was significantly lower than those getting ampicillin (7.4), P < 0.01, or placebo (7.0), P < 0.05. Only in the lactulose group was mean stool pH during therapy significantly decreased compared with the level off therapy (6.1 versus 7.1), P < 0.02. Lactulose shows promise for the treatment of shigella carriers but appears ineffective in treatment of acute shigellosis."}
{"id": "PMID:2099", "title": "Antimicrobial effect of simple lipids and the effect of pH and positive ions.", "content": "Various branched fatty acids, particularly those of iso-configuration, have been shown to possess fungistatic and bacteriostatic properties. On the basis of their swelling effect on hyphae of Fusarium roseum it was suggested that this is due to an increase in the permeability of the plasma membrane. The solubilization of fatty acids in membranes should be expected to be influenced by the degree of dissociation and the presence of counter ions. Therefore, the effects of pH and K(+), Na(+), and Ca(2+) ions were studied. It is demonstrated that the presence of the univalent ions, Na(+) and K(+), markedly enhances the fungistatic effect of iso-tetradecanoic acid, whereas the opposite effect is noted for the divalent ion, Ca(2+). The effects are particularly pronounced at high pH. Furthermore, the antimicrobial effect obtained from the combination of fatty acid and tetramethylthiuramdisulfide is significantly enhanced in the presence of 0.1 and 0.2% KCl.", "contents": "Antimicrobial effect of simple lipids and the effect of pH and positive ions. Various branched fatty acids, particularly those of iso-configuration, have been shown to possess fungistatic and bacteriostatic properties. On the basis of their swelling effect on hyphae of Fusarium roseum it was suggested that this is due to an increase in the permeability of the plasma membrane. The solubilization of fatty acids in membranes should be expected to be influenced by the degree of dissociation and the presence of counter ions. Therefore, the effects of pH and K(+), Na(+), and Ca(2+) ions were studied. It is demonstrated that the presence of the univalent ions, Na(+) and K(+), markedly enhances the fungistatic effect of iso-tetradecanoic acid, whereas the opposite effect is noted for the divalent ion, Ca(2+). The effects are particularly pronounced at high pH. Furthermore, the antimicrobial effect obtained from the combination of fatty acid and tetramethylthiuramdisulfide is significantly enhanced in the presence of 0.1 and 0.2% KCl."}
{"id": "PMID:2100", "title": "Regulation of citrate synthase activity of Saccharomyces cerevisiae.", "content": "Citrate synthase activity of Saccharomyces cerevisiae was determined by a radioactive assay procedure and the reaction product, 14C-citric acid, was identified by chromatographic techniques. ATP, d-ATP, GTP and NADH were most inhibitory to the citrate synthase invitro. The activity was inhibited to a lesser extent by ADP, UTP, and NADP whereas, AMP and CTP were much less inhibitory. NADH, like NAD, glutamic acid, glutamine, arginine, ornithine, proline, aspartic acid and alpha-ketoglutarate exhibited no inhibition. These results have been discussed in the light of the role of citrate synthase for the energy metabolism and glutamic acid biosynthesis.", "contents": "Regulation of citrate synthase activity of Saccharomyces cerevisiae. Citrate synthase activity of Saccharomyces cerevisiae was determined by a radioactive assay procedure and the reaction product, 14C-citric acid, was identified by chromatographic techniques. ATP, d-ATP, GTP and NADH were most inhibitory to the citrate synthase invitro. The activity was inhibited to a lesser extent by ADP, UTP, and NADP whereas, AMP and CTP were much less inhibitory. NADH, like NAD, glutamic acid, glutamine, arginine, ornithine, proline, aspartic acid and alpha-ketoglutarate exhibited no inhibition. These results have been discussed in the light of the role of citrate synthase for the energy metabolism and glutamic acid biosynthesis."}
{"id": "PMID:2101", "title": "Role of acetate metabolism in sporulation of Saccharomyces carlsbergensis.", "content": "Several aspects of the role of acetate metabolism in the sporulation of Saccaromyces carlsbergensis were investigated. Experiments in which the development of the respiratory system was either stimulated by growth on sugars to which the cells have to adapt, or inhibited by chloramphenicol suggested a correlation between respiratory development and sporulation. In cells in which the respiratory system has been repressed during growth, mitobhondrial protein synthesis and derepression are prerequisites for sporulation. When derepression is complete, sporulation no longer depends on mitochondrial protein synthesis. Incorporation experiments with acetate showed that this compound is an important source of intermediates for biosynthetic processes that occur during sporulation. Its incorporation into macromolecular fractions is tightly coupled to sporutlation.", "contents": "Role of acetate metabolism in sporulation of Saccharomyces carlsbergensis. Several aspects of the role of acetate metabolism in the sporulation of Saccaromyces carlsbergensis were investigated. Experiments in which the development of the respiratory system was either stimulated by growth on sugars to which the cells have to adapt, or inhibited by chloramphenicol suggested a correlation between respiratory development and sporulation. In cells in which the respiratory system has been repressed during growth, mitobhondrial protein synthesis and derepression are prerequisites for sporulation. When derepression is complete, sporulation no longer depends on mitochondrial protein synthesis. Incorporation experiments with acetate showed that this compound is an important source of intermediates for biosynthetic processes that occur during sporulation. Its incorporation into macromolecular fractions is tightly coupled to sporutlation."}
{"id": "PMID:2102", "title": "Bacterial and fungal growth in total parenteral nutrition solutions,.", "content": "The most serious complication of prolonged intravenous infusion of hypertonic dextrose and amino acids is infection. Frequently, the etiology is fungal rather than bacterial. Previous authors have suggested that bacterial survival and growth in the solutions is suppressed by (a) high dextrose concentration, (b) high osmolality, or (c) low pH. This paper presents evidence that proposals (a) and (b) are untenable and (c) is only partly responsible. We call attention to the presence of a factor that is antibacterial but not antifungal; namely, a high concentration of glycine.", "contents": "Bacterial and fungal growth in total parenteral nutrition solutions,. The most serious complication of prolonged intravenous infusion of hypertonic dextrose and amino acids is infection. Frequently, the etiology is fungal rather than bacterial. Previous authors have suggested that bacterial survival and growth in the solutions is suppressed by (a) high dextrose concentration, (b) high osmolality, or (c) low pH. This paper presents evidence that proposals (a) and (b) are untenable and (c) is only partly responsible. We call attention to the presence of a factor that is antibacterial but not antifungal; namely, a high concentration of glycine."}
{"id": "PMID:2103", "title": "New medium for isolating iron-oxidizing and heterotrophic acidophilic bacteria from acid mine drainage.", "content": "A new solid medium is described for growing iron and heterotrophic bacteria from acid mine drainage (AMD). Examination of AMD from five states revealed several kinds of colonies of iron-oxidizing bacteria: (i) smooth, (ii) smooth with secondary growth sectors or branching, (iii) star-shaped, (iv) radiating lobe, and (v) flat-rough. All AMD samples yielded whitish colonies that could not use ferrous iron, sulfur, or hydrogen, nor could they grow on nutrient agar, brain heart infusion agar, or Trypticase soy agar. Glucose and sucrose supported growth if the sugar-salts medium was at pH 3.0. The new iron medium has several advantages over others: (i) easy preparation, (ii) rapid growth, (iii) larger colonies, (iv) differentiation of colony morphology, and (v) detection of a new group of heterotrophic acidophilic bacteria.", "contents": "New medium for isolating iron-oxidizing and heterotrophic acidophilic bacteria from acid mine drainage. A new solid medium is described for growing iron and heterotrophic bacteria from acid mine drainage (AMD). Examination of AMD from five states revealed several kinds of colonies of iron-oxidizing bacteria: (i) smooth, (ii) smooth with secondary growth sectors or branching, (iii) star-shaped, (iv) radiating lobe, and (v) flat-rough. All AMD samples yielded whitish colonies that could not use ferrous iron, sulfur, or hydrogen, nor could they grow on nutrient agar, brain heart infusion agar, or Trypticase soy agar. Glucose and sucrose supported growth if the sugar-salts medium was at pH 3.0. The new iron medium has several advantages over others: (i) easy preparation, (ii) rapid growth, (iii) larger colonies, (iv) differentiation of colony morphology, and (v) detection of a new group of heterotrophic acidophilic bacteria."}
{"id": "PMID:2104", "title": "Effect of initial pH on aflatoxin production.", "content": "The effect of initial pH on aflatoxin production by Aspergillus parasiticus NRRL 2999 was examined in a semisynthetic medium. Maximal growth, aflatoxin production, and aflatoxin production per unit of growth occurred at initial pH levels of 5.0, 6.0, and 7.0 respectively. Initial pH levels less than pH 6.0 favored production of the B toxins, whereas levels greater than pH 6.0 favored production of the G toxins.", "contents": "Effect of initial pH on aflatoxin production. The effect of initial pH on aflatoxin production by Aspergillus parasiticus NRRL 2999 was examined in a semisynthetic medium. Maximal growth, aflatoxin production, and aflatoxin production per unit of growth occurred at initial pH levels of 5.0, 6.0, and 7.0 respectively. Initial pH levels less than pH 6.0 favored production of the B toxins, whereas levels greater than pH 6.0 favored production of the G toxins."}
{"id": "PMID:2105", "title": "High-temperature production of protein-enriched feed from cassava by fungi.", "content": "A simple, nonaseptic, low-cast process for the conversion of cassava, a starchy tropical root crop, into microbial protein for use as animal feed was sought. Screening tests culminated in the isolation of a thermotolerant, amylase-producing mold, designated I-21, which was identified as Aspergillus fumigatus. The optimum pH for protein synthesis was 3-5, but the optimum temperature was less than the desired temperature (larger than or equal to 45 C) required for a nonaseptic fermentation. A. fumigatus I-21 and its asporogenous mutant I-21A grew equally well in a medium prepared from whole cassava roots with a mean protein doubling time at 45 C and pH 3.5 of 3.5 h. In batch culture, approximately 4% carbohydrate, supplied as whole cassava, could be feremented in 20 h, giving a final yield of 24 g of dry product, containing 36.9% crude protein, per liter. The conversion of carbohydrate used to crude protein was 22.1%. When determined as amino acids, the protein content of the product, which contained cassava bark and other unfermented residues, was 27.1%. With urea as the nitrogen source, no pH control was necessary. Preliminary data indicated that medium prepared from whole cassava roots was inhibitory to the mold unless the cassava pulp was heated to 70 C immediately after being ground. Heating to 70 C was required to gelatinize the starch and permit its complete utilization.", "contents": "High-temperature production of protein-enriched feed from cassava by fungi. A simple, nonaseptic, low-cast process for the conversion of cassava, a starchy tropical root crop, into microbial protein for use as animal feed was sought. Screening tests culminated in the isolation of a thermotolerant, amylase-producing mold, designated I-21, which was identified as Aspergillus fumigatus. The optimum pH for protein synthesis was 3-5, but the optimum temperature was less than the desired temperature (larger than or equal to 45 C) required for a nonaseptic fermentation. A. fumigatus I-21 and its asporogenous mutant I-21A grew equally well in a medium prepared from whole cassava roots with a mean protein doubling time at 45 C and pH 3.5 of 3.5 h. In batch culture, approximately 4% carbohydrate, supplied as whole cassava, could be feremented in 20 h, giving a final yield of 24 g of dry product, containing 36.9% crude protein, per liter. The conversion of carbohydrate used to crude protein was 22.1%. When determined as amino acids, the protein content of the product, which contained cassava bark and other unfermented residues, was 27.1%. With urea as the nitrogen source, no pH control was necessary. Preliminary data indicated that medium prepared from whole cassava roots was inhibitory to the mold unless the cassava pulp was heated to 70 C immediately after being ground. Heating to 70 C was required to gelatinize the starch and permit its complete utilization."}
{"id": "PMID:2106", "title": "Removal of algae from Florida lakes by magnetic filtration.", "content": "Magnetic filtration was used for the removal of algal populations present in five lakes located in the vicinity of Gainesville, Fla. It was found that the use of this technique enabled a good removal (94%) of algal cells from three lakes where the pH was around 7. The other two lakes, with a higher pH, displayed a lower removal. However, the treatment was greatly improved by lowering the pH from 9.5 to 6.5.", "contents": "Removal of algae from Florida lakes by magnetic filtration. Magnetic filtration was used for the removal of algal populations present in five lakes located in the vicinity of Gainesville, Fla. It was found that the use of this technique enabled a good removal (94%) of algal cells from three lakes where the pH was around 7. The other two lakes, with a higher pH, displayed a lower removal. However, the treatment was greatly improved by lowering the pH from 9.5 to 6.5."}
{"id": "PMID:2107", "title": "Factors influencing detection and enumeration of Pseudomonas aeruginosa by most-probable-number and membrane filtration techniques.", "content": "Most-probable-number (MPN) and membrane filtration (mF) techniques were evaluated with respect to selectivity, sensitivity, and efficiency in recovering Pseudomonas aeruginosa strains in hospital fluids and extramural water environments. Known numbers of cells of a naturally occurring strain of P. aeruginosa maintained in distilled water or cells subcultured on Standard Methods agar were added to test samples containing various types and levels of background microbial contamiants. Environmental samples containing unknown numbers of P. aeruginosa strains also were tested. Asparagine and acetamide broths were employed as presumptive media in MPN tests, and mPA and Pseudosel agars were used in mF assays. Statistical analyses of data showed the superiority and comparability of the asparagine-MPN and mPA-mF systems. Greater precision and accuracy were consistently obtained in either assay technique by the use of naturally occurring cells as test organisms. The type of filter and nature of diluents employed, as well as pH of assay media, were found to greatly influence both recovery and developemnt of characteristic colonial morphology in the mPA-mF system.", "contents": "Factors influencing detection and enumeration of Pseudomonas aeruginosa by most-probable-number and membrane filtration techniques. Most-probable-number (MPN) and membrane filtration (mF) techniques were evaluated with respect to selectivity, sensitivity, and efficiency in recovering Pseudomonas aeruginosa strains in hospital fluids and extramural water environments. Known numbers of cells of a naturally occurring strain of P. aeruginosa maintained in distilled water or cells subcultured on Standard Methods agar were added to test samples containing various types and levels of background microbial contamiants. Environmental samples containing unknown numbers of P. aeruginosa strains also were tested. Asparagine and acetamide broths were employed as presumptive media in MPN tests, and mPA and Pseudosel agars were used in mF assays. Statistical analyses of data showed the superiority and comparability of the asparagine-MPN and mPA-mF systems. Greater precision and accuracy were consistently obtained in either assay technique by the use of naturally occurring cells as test organisms. The type of filter and nature of diluents employed, as well as pH of assay media, were found to greatly influence both recovery and developemnt of characteristic colonial morphology in the mPA-mF system."}
{"id": "PMID:2108", "title": "Heat resistance of ileal loop reactive Bacillus cereus strains isolated from commercially canned food.", "content": "Sporeformers isolated from a commercially canned food were identified as Bacillus cereus, lactose-positive variants. The thermal resistance of spore crops produced from each of two representative cultures was determined in 0.067 M phosphate buffer at pH 7.0. The D121.1 values for one isolate were approximately 0.03 min (z = 9.9C), whereas the D121.1 values for the other isolate were 2.35 min (z = 7.9 C). Thermal inactivation results for heat-stressed isolates from each strain showed no significant alteration in heat resistance from that of the two parent spore crops. Both isolates were reactive when injected into the ligated rabbit ileum.", "contents": "Heat resistance of ileal loop reactive Bacillus cereus strains isolated from commercially canned food. Sporeformers isolated from a commercially canned food were identified as Bacillus cereus, lactose-positive variants. The thermal resistance of spore crops produced from each of two representative cultures was determined in 0.067 M phosphate buffer at pH 7.0. The D121.1 values for one isolate were approximately 0.03 min (z = 9.9C), whereas the D121.1 values for the other isolate were 2.35 min (z = 7.9 C). Thermal inactivation results for heat-stressed isolates from each strain showed no significant alteration in heat resistance from that of the two parent spore crops. Both isolates were reactive when injected into the ligated rabbit ileum."}
{"id": "PMID:2109", "title": "Kinetics of a bacterial culture growth: validity of the affinity rule in biological systems.", "content": "The kinetic study of a process is usually performed by measuring a convenient intensive property, P, as a function of time. The \"affinity rule\" states that, when a given process takes place under different external constraints (e.g., different temperatures, pressures, pH values, etc.), the various P versus time curves are related by an affinity transformation parallel to the time axis: in other words the P versus log time curves are parallel and can be superimposed by translation. The validity of the rule has been extensively tested in chemical and physiochemical processes, but there is no evidence as yet that it extends to biological systems. The present paper shows that the rule is indeed valid for the kinetics of growth of an Escherichia coli culture at various temperatures and pH values. More extended experiments are necessary to prove or disprove the general validity of the rule in biological systems, but its practical interest is evident: whenever it is valid it will be possible, from a very small number of measurements, to predict the complete behavior of the system in a number of various external conditions", "contents": "Kinetics of a bacterial culture growth: validity of the affinity rule in biological systems. The kinetic study of a process is usually performed by measuring a convenient intensive property, P, as a function of time. The \"affinity rule\" states that, when a given process takes place under different external constraints (e.g., different temperatures, pressures, pH values, etc.), the various P versus time curves are related by an affinity transformation parallel to the time axis: in other words the P versus log time curves are parallel and can be superimposed by translation. The validity of the rule has been extensively tested in chemical and physiochemical processes, but there is no evidence as yet that it extends to biological systems. The present paper shows that the rule is indeed valid for the kinetics of growth of an Escherichia coli culture at various temperatures and pH values. More extended experiments are necessary to prove or disprove the general validity of the rule in biological systems, but its practical interest is evident: whenever it is valid it will be possible, from a very small number of measurements, to predict the complete behavior of the system in a number of various external conditions"}
{"id": "PMID:2110", "title": "Beclomethasone dipropionate aerosol in treatment of hay fever in children.", "content": "Eighteen children suffering from hay fever were treated with intra-nasal beclomethasone dipropionate (400 mug/day) and an identical placebo aerosol in a double-blind cross-over trial. 17 of the children preferred the intranasal beclomethasone dipropionate, one had no preference, none preferred the placebo. The effect on the nasal symptoms was impressive. Symptom scores decreased, on average, to 12% and the number of antihistamine tablets taken to 18% of the pretreatment amount. Some beneficial effect on eye symptoms was also discernible, possibly due to an indirect influence from the nasal mucosa via the nasolacrimal reflex. Adrenal function was not affected. It was concluded that 400 mug beclomethasone dipropionate given intranasally daily for some weeks is an effective and safe treatment for hay fever in children.", "contents": "Beclomethasone dipropionate aerosol in treatment of hay fever in children. Eighteen children suffering from hay fever were treated with intra-nasal beclomethasone dipropionate (400 mug/day) and an identical placebo aerosol in a double-blind cross-over trial. 17 of the children preferred the intranasal beclomethasone dipropionate, one had no preference, none preferred the placebo. The effect on the nasal symptoms was impressive. Symptom scores decreased, on average, to 12% and the number of antihistamine tablets taken to 18% of the pretreatment amount. Some beneficial effect on eye symptoms was also discernible, possibly due to an indirect influence from the nasal mucosa via the nasolacrimal reflex. Adrenal function was not affected. It was concluded that 400 mug beclomethasone dipropionate given intranasally daily for some weeks is an effective and safe treatment for hay fever in children."}
{"id": "PMID:2111", "title": "The influence of oxyhemoglobin affinity on tissue oxygen consumption.", "content": "In an intact animal or patient, any shift in oxyhemoglobin affinity is inevitably associated with concurrent fluctuation in numerous other determinants of oxygen delivery. For this reason, the influence of hemoglobin affinity for oxygen on tissue oxygen consumption has been incompletely evaluated. The purpose of this study was to investigate the influence of oxyhemoglobin affinity as the sole variable of oxygen delivery in an isolated perfused canine hindlimb. A membrane lung system which allowed precise control of blood flow, temperature, arterial oxygen content and arterial pH was established. Twelve isolated canine hindlimbs were alternatively perfused with autologous stored (left-shifted)  and fresh (right-shifted) blood in paralled perfusion systems. The 2,3-DPG concentrations, P50 and oxygen consumptions were significantly different in the two paralled perfusion systems. A decreased hemoglobin affinity for oxygen appeared to permit increased oxygen off-loading at the tissue level.", "contents": "The influence of oxyhemoglobin affinity on tissue oxygen consumption. In an intact animal or patient, any shift in oxyhemoglobin affinity is inevitably associated with concurrent fluctuation in numerous other determinants of oxygen delivery. For this reason, the influence of hemoglobin affinity for oxygen on tissue oxygen consumption has been incompletely evaluated. The purpose of this study was to investigate the influence of oxyhemoglobin affinity as the sole variable of oxygen delivery in an isolated perfused canine hindlimb. A membrane lung system which allowed precise control of blood flow, temperature, arterial oxygen content and arterial pH was established. Twelve isolated canine hindlimbs were alternatively perfused with autologous stored (left-shifted)  and fresh (right-shifted) blood in paralled perfusion systems. The 2,3-DPG concentrations, P50 and oxygen consumptions were significantly different in the two paralled perfusion systems. A decreased hemoglobin affinity for oxygen appeared to permit increased oxygen off-loading at the tissue level."}
{"id": "PMID:2112", "title": "The relationship between muscle surface pH and oxygen transport.", "content": "The relationship between muscle surface pH (pHM) and the arterial-venous oxygen content difference (AVO2D) was studied in 4 patients undergoing reconstructive arterial surgery and in 6 patients undergoing acute normovolemic hemodilution. There was a consistent inverse relation between pHM in the ischemic lower extremity and the femoral AVO2D before, during and after aortic clamping. There was also an inverse relation between AVO2D and pHM during hemodilution. These data confirm that pHM is a reliable indicator of tissue perfusion and correlates with the AVO2D.", "contents": "The relationship between muscle surface pH and oxygen transport. The relationship between muscle surface pH (pHM) and the arterial-venous oxygen content difference (AVO2D) was studied in 4 patients undergoing reconstructive arterial surgery and in 6 patients undergoing acute normovolemic hemodilution. There was a consistent inverse relation between pHM in the ischemic lower extremity and the femoral AVO2D before, during and after aortic clamping. There was also an inverse relation between AVO2D and pHM during hemodilution. These data confirm that pHM is a reliable indicator of tissue perfusion and correlates with the AVO2D."}
{"id": "PMID:2113", "title": "Sodium nitroprusside as a coronary vasodilator in man: a comparison of the effects of sodium nitroprusside and papaverine hydrochloride on aortocoronary saphenous vein graft flow.", "content": "Blood flow in aortocoronary saphenous vein grafts was studied in response to intragraft injection of sodium nitroprusside and papaverine hydrochloride. Following injection of 50 mug of sodium nitroprusside, mean graft flow increased from 40.1 +/- 4.5 to 81.3 +/- 8.5 ml per minute. Administration of 30 mg of papaverine hydrochloride caused mean graft flow to rise from 35.4 +/- 3.9 to 70 +/- 7.9 ml per minute. Sodium nitroprusside increases aortocoronary graft flow, the doubling effect of 50 mug of the drug being of the same order of magnitude as that induced by 30 mg of papaverine hydrochloride.", "contents": "Sodium nitroprusside as a coronary vasodilator in man: a comparison of the effects of sodium nitroprusside and papaverine hydrochloride on aortocoronary saphenous vein graft flow. Blood flow in aortocoronary saphenous vein grafts was studied in response to intragraft injection of sodium nitroprusside and papaverine hydrochloride. Following injection of 50 mug of sodium nitroprusside, mean graft flow increased from 40.1 +/- 4.5 to 81.3 +/- 8.5 ml per minute. Administration of 30 mg of papaverine hydrochloride caused mean graft flow to rise from 35.4 +/- 3.9 to 70 +/- 7.9 ml per minute. Sodium nitroprusside increases aortocoronary graft flow, the doubling effect of 50 mug of the drug being of the same order of magnitude as that induced by 30 mg of papaverine hydrochloride."}
{"id": "PMID:2114", "title": "Comparative evaluation of a new disposable rotating membrane oxygenator with bubble oxygenator.", "content": "The comparative in vivo performance of adult-size bubble and rotating membrane oxygenators was evaluated during closed-chest cardiopulmonary bypass for six hours in two groups of dogs. The results show that the rotating membrane oxygenator is efficient in oxygen and carbon dioxide transfer with minimal trauma to blood, while platelet destruction and hemolysis were marked with the bubble oxygenator. Cerebral, cardiac, and respiratory complications were frequent with the bubble oxygenator and absent with the membrane oxygenator.", "contents": "Comparative evaluation of a new disposable rotating membrane oxygenator with bubble oxygenator. The comparative in vivo performance of adult-size bubble and rotating membrane oxygenators was evaluated during closed-chest cardiopulmonary bypass for six hours in two groups of dogs. The results show that the rotating membrane oxygenator is efficient in oxygen and carbon dioxide transfer with minimal trauma to blood, while platelet destruction and hemolysis were marked with the bubble oxygenator. Cerebral, cardiac, and respiratory complications were frequent with the bubble oxygenator and absent with the membrane oxygenator."}
{"id": "PMID:2115", "title": "Adrenergic drug-receptor interaction in the presence of strontium (Sr++) in mammalian myocardium.", "content": "The specificity of Ca++ for the interaction of beta adrenergic agonists with their receptors in rabbit right atrial muscle was evaluated. This was accomplished by substituting Ca++ by an equimolar concentration of Sr++. Dose-response curves which demonstrate the effect of norepinephrine and isoproterenol on the rate of electrical activity in the presence of Ca++ or Sr++ were made. In addition, the antagonistic action of propranolol (1 X 10(-7) M) in a Ca++-containing or Sr++-containing medium was determined. The results clearly demonstrate that Sr++ can effectively substitute for Ca++ in maintaining electrical and mechanical activity in cardiac muscle. Also, norepinephrine and isoproterenol can increase the rate of electrical activity in a Ca++ or Sr++-containing medium. This effect of these beta agonists is mediated through the beta-receptors since propranolol effectively blocked their action. It appears that Ca++ per se is not required for beta agonist or antagonist-receptor interaction in cardiac muscle. The results are discussed in relation to the dependency on extracellular Ca++ for beta agonists to cause a change in the rate of electrical activity after receptor occupancy.", "contents": "Adrenergic drug-receptor interaction in the presence of strontium (Sr++) in mammalian myocardium. The specificity of Ca++ for the interaction of beta adrenergic agonists with their receptors in rabbit right atrial muscle was evaluated. This was accomplished by substituting Ca++ by an equimolar concentration of Sr++. Dose-response curves which demonstrate the effect of norepinephrine and isoproterenol on the rate of electrical activity in the presence of Ca++ or Sr++ were made. In addition, the antagonistic action of propranolol (1 X 10(-7) M) in a Ca++-containing or Sr++-containing medium was determined. The results clearly demonstrate that Sr++ can effectively substitute for Ca++ in maintaining electrical and mechanical activity in cardiac muscle. Also, norepinephrine and isoproterenol can increase the rate of electrical activity in a Ca++ or Sr++-containing medium. This effect of these beta agonists is mediated through the beta-receptors since propranolol effectively blocked their action. It appears that Ca++ per se is not required for beta agonist or antagonist-receptor interaction in cardiac muscle. The results are discussed in relation to the dependency on extracellular Ca++ for beta agonists to cause a change in the rate of electrical activity after receptor occupancy."}
{"id": "PMID:2116", "title": "Effects of isoprenaline and phenylephrine on plasma potassium: role of the liver.", "content": "A dog liver preparation in situ was used. Intravenous infusion of isoprenaline caused a decrease of plasma potassium levels, which was preceded, in some of the animals infused with higher doses, by a rise in plasma potassium. Propranolol abolished both these effects of isoprenaline, whereas phentolamine was devoided of effects. Liver potassium was not affected by isoprenaline infusions. Phenylephrine caused release of potassium from the liver; this effect was blocked by phentolamine, but not by propranolol. Combination of phenylephrine and isoprenaline induced a super-additive hyperkalemia. Analysis of these results led to the conclusion that the rise in plasma potassium due to phenylephrine might reflect a direct kalemotropic effect and an indirect hypoxemic effect. Isoprenaline seems to increase the hypoxemia caused by phenylephrine by opening the intrahepatic vascular shunts.", "contents": "Effects of isoprenaline and phenylephrine on plasma potassium: role of the liver. A dog liver preparation in situ was used. Intravenous infusion of isoprenaline caused a decrease of plasma potassium levels, which was preceded, in some of the animals infused with higher doses, by a rise in plasma potassium. Propranolol abolished both these effects of isoprenaline, whereas phentolamine was devoided of effects. Liver potassium was not affected by isoprenaline infusions. Phenylephrine caused release of potassium from the liver; this effect was blocked by phentolamine, but not by propranolol. Combination of phenylephrine and isoprenaline induced a super-additive hyperkalemia. Analysis of these results led to the conclusion that the rise in plasma potassium due to phenylephrine might reflect a direct kalemotropic effect and an indirect hypoxemic effect. Isoprenaline seems to increase the hypoxemia caused by phenylephrine by opening the intrahepatic vascular shunts."}
{"id": "PMID:2117", "title": "Benzodiazepines and amphetamine on avoidance behaviour in mice.", "content": "Six benzodiazepine derivatives, given alone or in combination with amphetamine, were tested in mice subjected to five 100-trial avoidance sessions in the shuttle-box. All derivatives, execpt bromazepam, showed some facilitating effects on avoidance responding when given alone. Facilitation was particularly evident following the administration of chlordiazepoxide (2.5 mg/kg), medazepam (10 mg/kg) and nitrazepam (0.25, 0.5 and 1 mg/kg). Favourable effects were obtained by combining each benzodiazepine compound with amphetamine. The levels of avoidance respinses were usually higher under benzodiazepine-amphetamine combinations than under benzodiazepines alone.", "contents": "Benzodiazepines and amphetamine on avoidance behaviour in mice. Six benzodiazepine derivatives, given alone or in combination with amphetamine, were tested in mice subjected to five 100-trial avoidance sessions in the shuttle-box. All derivatives, execpt bromazepam, showed some facilitating effects on avoidance responding when given alone. Facilitation was particularly evident following the administration of chlordiazepoxide (2.5 mg/kg), medazepam (10 mg/kg) and nitrazepam (0.25, 0.5 and 1 mg/kg). Favourable effects were obtained by combining each benzodiazepine compound with amphetamine. The levels of avoidance respinses were usually higher under benzodiazepine-amphetamine combinations than under benzodiazepines alone."}
{"id": "PMID:2118", "title": "[Age related effects of furosemide in the rat].", "content": "Furosemide (6 mg/kg i.p.) increases the renal excretion of water, osmotic active substances, sodium and chloride in 5 to 33 day old rats more than in adults. The dose-response-relations are the same in rats of all age groups: 6 mg/kg of furosemide i.p. are very effective, an increase in dose to 30-60 mg/kg i.p. is not followed by a significantly higher efficacy. The increase in the renal excretion of potassium, hydrogen ions, ammonium and hydrogen carbonate by furosemide is also small in young rats.", "contents": "[Age related effects of furosemide in the rat]. Furosemide (6 mg/kg i.p.) increases the renal excretion of water, osmotic active substances, sodium and chloride in 5 to 33 day old rats more than in adults. The dose-response-relations are the same in rats of all age groups: 6 mg/kg of furosemide i.p. are very effective, an increase in dose to 30-60 mg/kg i.p. is not followed by a significantly higher efficacy. The increase in the renal excretion of potassium, hydrogen ions, ammonium and hydrogen carbonate by furosemide is also small in young rats."}
{"id": "PMID:2119", "title": "The effect of sulfhydryl reagents on the heart rate and coronary flow of the isolated perfused guinea-pig heart.", "content": "The action of a number of compounds able to react with thiols was tested on guinea-pig hearts perfused at constant pressure. The SH reagents used were NaNO2, oxidized glutathione, cystamine, diamide, 1,5-difluoro-2,4-dinitrobenzene, nitroglycerol, sodium nitroferricyanide and HgCl2. 6,6'-Dithiodinicotinic acid, an SH reagent that does not penetrate the cell, produced no effect. All the other SH reagents produced an increase in coronary flow. All except oxidized glutathione and nitroglycerol increased the heart rate. The increase in heart rate and oxygen consumption could be completely blocked by dichloroisoproterenol; the increase in coronary flow was not affected. Difluorodinitrobenzene, diamide, cystamine and NaNO2 significantly decreased the acid-soluble thiol content of the heart. For these compounds, there was a significant correlation between the decrease in coronary flow and the decrease in thiols. We conclude that in the isolated heart, most SH reagents, if used at the appropriate concentration, will increase the heart rate, probably by relaasing catecholamines. They will also decrease the coronary resistance, probably by a direct effect on the coronary vessels.", "contents": "The effect of sulfhydryl reagents on the heart rate and coronary flow of the isolated perfused guinea-pig heart. The action of a number of compounds able to react with thiols was tested on guinea-pig hearts perfused at constant pressure. The SH reagents used were NaNO2, oxidized glutathione, cystamine, diamide, 1,5-difluoro-2,4-dinitrobenzene, nitroglycerol, sodium nitroferricyanide and HgCl2. 6,6'-Dithiodinicotinic acid, an SH reagent that does not penetrate the cell, produced no effect. All the other SH reagents produced an increase in coronary flow. All except oxidized glutathione and nitroglycerol increased the heart rate. The increase in heart rate and oxygen consumption could be completely blocked by dichloroisoproterenol; the increase in coronary flow was not affected. Difluorodinitrobenzene, diamide, cystamine and NaNO2 significantly decreased the acid-soluble thiol content of the heart. For these compounds, there was a significant correlation between the decrease in coronary flow and the decrease in thiols. We conclude that in the isolated heart, most SH reagents, if used at the appropriate concentration, will increase the heart rate, probably by relaasing catecholamines. They will also decrease the coronary resistance, probably by a direct effect on the coronary vessels."}
{"id": "PMID:2120", "title": "Metabolic inhibition and adrenoceptor interconversion.", "content": "The adrenergic receptor responses of isolated strips of iris dilator muscle from rabbits were studied. An alpha agonist, norepinephrine and a beta agonist, isoprenaline, were used to assess adrenergic sensitivity before and after pretreatment of tissues with metabolic inhibitors at 22, 29 and 37 degrees C. The metabolic inhibitors used were iodoacetic acid and dinitrophenol. Temperature change altered adrenoceptor sensitivity in the same manner before and after metabolic inhibition. Iodoacetic acid (10.4 mug/ml) pretreatment increased both alpha and beta responses. Dinitrophenol (1.8 mug/ml) pretreatment increased alpha and decreased beta responsiveness. The results obtained indicate that some metabolic process altered by dinitrophenol may be involved in this adrenoceptor interconversion seen when temperature is changed. This supports the theory that local environment determines the drug sensitivity (alpha or beta) of a single adrenergic receptor.", "contents": "Metabolic inhibition and adrenoceptor interconversion. The adrenergic receptor responses of isolated strips of iris dilator muscle from rabbits were studied. An alpha agonist, norepinephrine and a beta agonist, isoprenaline, were used to assess adrenergic sensitivity before and after pretreatment of tissues with metabolic inhibitors at 22, 29 and 37 degrees C. The metabolic inhibitors used were iodoacetic acid and dinitrophenol. Temperature change altered adrenoceptor sensitivity in the same manner before and after metabolic inhibition. Iodoacetic acid (10.4 mug/ml) pretreatment increased both alpha and beta responses. Dinitrophenol (1.8 mug/ml) pretreatment increased alpha and decreased beta responsiveness. The results obtained indicate that some metabolic process altered by dinitrophenol may be involved in this adrenoceptor interconversion seen when temperature is changed. This supports the theory that local environment determines the drug sensitivity (alpha or beta) of a single adrenergic receptor."}
{"id": "PMID:2121", "title": "The influence of temperature increase, elevation of extracellular h+-concentration, and of triiodothyronine on the actions of phenylephrine, histamine, and beta-sympathomimetic drugs on rabbit aortic strips.", "content": "In the isolated preparation from the rabbit thoracic aorta, the affinities of the vasoconstrictor agents phenylephrine and histamine, as well as of the vasodilator beta-sympathomimetic drugs isoprenaline, fenoterol (TH 1165a), terbutaline, and salbutamol under the conditions of temperature increase, triiodothyronine and decrease of extracellular pH were investigated. It was observed that (1) a temperature increase from 25 degrees to 42 degrees C significantly indreased the maximal tension evoked by histamine, whereas that induced by the alpha-sympathomimetic drug phenylephrine was not altered significantly; the maximal relaxation caused by beta-sympathomimetic drugs either at 25 degrees or at 42 degrees C did not differ from one another; (2) the affinities of histamine, phenylephrine and of the beta-sympathomimetic drugs isoprenaline, fenoterol, terbutaline, and salbutamol each were comparable at either 25 degrees or 42 degrees C; the rank order of efficacy of the beta-sympathomimetic drugs is isoprenaline greater than fenoterol greater than salbutamol greater than terbutaline; (3) a decrease of the pH from 7.37 to 7.15 diminished the affinities of histamine and of the beta sympathomimetic drugs whereas that of the alpha-adrenergic drug phenylephrine was not altered. A further decrease of the pH to 6.8 diminished additionally the affinity of histamine and of isoprenaline, and especially that of the other beta-sympathomimetic drugs to such an extent that in the latter case complete dose-response curves could not be determined any more; (4) pretreatment of the animals with 0.4 mg/kg of triiodothyronine (T3) for two days, which strongly depressed the tension induced by either histamine or phenylephrine, did not alter the affinity of both drugs; T3 in vitro (10(-6) M) only diminished the affinity of histamine but left that of phenylephrine unaltered; pretreatment for two days with 0.2 mg/kg of T3 yielded a significant diminution of the pD2-values for two beta-sympathomimetic drugs investigated, namely isoprenaline and fenoterol; also the administration of T3 in vitro in a final concentration of 10(-6) M resulted in a diminution of the affinity of both beta-sympathomimetic drugs; (5) the results obtained show that also on the aorta beta-adrenoceptor stimulants are dependent on the metabolic state while alpha-adrenoceptor stimulants are not.", "contents": "The influence of temperature increase, elevation of extracellular h+-concentration, and of triiodothyronine on the actions of phenylephrine, histamine, and beta-sympathomimetic drugs on rabbit aortic strips. In the isolated preparation from the rabbit thoracic aorta, the affinities of the vasoconstrictor agents phenylephrine and histamine, as well as of the vasodilator beta-sympathomimetic drugs isoprenaline, fenoterol (TH 1165a), terbutaline, and salbutamol under the conditions of temperature increase, triiodothyronine and decrease of extracellular pH were investigated. It was observed that (1) a temperature increase from 25 degrees to 42 degrees C significantly indreased the maximal tension evoked by histamine, whereas that induced by the alpha-sympathomimetic drug phenylephrine was not altered significantly; the maximal relaxation caused by beta-sympathomimetic drugs either at 25 degrees or at 42 degrees C did not differ from one another; (2) the affinities of histamine, phenylephrine and of the beta-sympathomimetic drugs isoprenaline, fenoterol, terbutaline, and salbutamol each were comparable at either 25 degrees or 42 degrees C; the rank order of efficacy of the beta-sympathomimetic drugs is isoprenaline greater than fenoterol greater than salbutamol greater than terbutaline; (3) a decrease of the pH from 7.37 to 7.15 diminished the affinities of histamine and of the beta sympathomimetic drugs whereas that of the alpha-adrenergic drug phenylephrine was not altered. A further decrease of the pH to 6.8 diminished additionally the affinity of histamine and of isoprenaline, and especially that of the other beta-sympathomimetic drugs to such an extent that in the latter case complete dose-response curves could not be determined any more; (4) pretreatment of the animals with 0.4 mg/kg of triiodothyronine (T3) for two days, which strongly depressed the tension induced by either histamine or phenylephrine, did not alter the affinity of both drugs; T3 in vitro (10(-6) M) only diminished the affinity of histamine but left that of phenylephrine unaltered; pretreatment for two days with 0.2 mg/kg of T3 yielded a significant diminution of the pD2-values for two beta-sympathomimetic drugs investigated, namely isoprenaline and fenoterol; also the administration of T3 in vitro in a final concentration of 10(-6) M resulted in a diminution of the affinity of both beta-sympathomimetic drugs; (5) the results obtained show that also on the aorta beta-adrenoceptor stimulants are dependent on the metabolic state while alpha-adrenoceptor stimulants are not."}
{"id": "PMID:2122", "title": "Influence of pH on the contractor effect of convulsant barbiturate on frog lung.", "content": "Pentobarbial, thiopental and the convulsant 5-ethyl-5-(2-cyclohexylidene\u00ebthyl) barbituric acid (CHEB) were tested for contractor effect on the isolated lung of the fullfrog at pH 7.0 (7% CO2 and 20 mM HCO3-) and pH 8.4 (0.3% CO2 and 20mM HCO3-). CHEB was a potent contractor, thiopental a feeble contractor, and pentobarbital lacked contractor effect. The contractor potencies of both CHEB and thiopental were greater at the more acid pH. The potencies of formally charged agonists such as acetylcholine and K+ were not altered by the pH differences employed in these experiments. The pKa of CHEB was found to be 8.18 at 15 degrees C and 8.03 at 27 degrees C. Calculation of concentration-effect relationships of ionized and nonionized CHEB showed that only the nonionized CHEB was responsible for the contractor effect.", "contents": "Influence of pH on the contractor effect of convulsant barbiturate on frog lung. Pentobarbial, thiopental and the convulsant 5-ethyl-5-(2-cyclohexylidene\u00ebthyl) barbituric acid (CHEB) were tested for contractor effect on the isolated lung of the fullfrog at pH 7.0 (7% CO2 and 20 mM HCO3-) and pH 8.4 (0.3% CO2 and 20mM HCO3-). CHEB was a potent contractor, thiopental a feeble contractor, and pentobarbital lacked contractor effect. The contractor potencies of both CHEB and thiopental were greater at the more acid pH. The potencies of formally charged agonists such as acetylcholine and K+ were not altered by the pH differences employed in these experiments. The pKa of CHEB was found to be 8.18 at 15 degrees C and 8.03 at 27 degrees C. Calculation of concentration-effect relationships of ionized and nonionized CHEB showed that only the nonionized CHEB was responsible for the contractor effect."}
{"id": "PMID:2123", "title": "Action of six commonly used benzodiazepines on isolated guinea-pig ileum preparation.", "content": "The spasmolytic activity of six commonly used benzodiazepines was investigated on isolated guinea-pig ileum preparation. All six substances proved to be non-competitive antagonists of carbachol and barium chloride, the pD'2 values ranging between 3.23 and 4.37 in the presence of either agonist. The significance of these findings is discussed.", "contents": "Action of six commonly used benzodiazepines on isolated guinea-pig ileum preparation. The spasmolytic activity of six commonly used benzodiazepines was investigated on isolated guinea-pig ileum preparation. All six substances proved to be non-competitive antagonists of carbachol and barium chloride, the pD'2 values ranging between 3.23 and 4.37 in the presence of either agonist. The significance of these findings is discussed."}
{"id": "PMID:2124", "title": "Electrical events associated with the action of nicotine at the adrenergic nerve terminal.", "content": "Nicotine perfused through the coronary circulation of the isolated atropinized cat heart elicits antidromic activity in the cardiac sympathetic nerves. The pattern of discharge varies in a complex fashion with dose. At low concentrations, activity may last up to 10 min, whereas at high doses the antidromic response may last only a few seconds. Sympathetic transmitter is released into the perfusion fluid. There is dissociation between the amount of transmitter that overflows from the heart and the total antidromic activity with increasing dose of nicotine. With smaller doses of nicotine, the magnitude of the antidromic activity probably indicates the level of depolarization of the nerve terminal. Injection of greater doses of nicotine causes still greater transmitter release but not the generation of antidromic impulses, due presumably to persistent depolarization below a critical level. During the nicotine infusion and immediately afterwards, the antidromic response to acetylcholine and the effector responses associated with the adrenergic transmitter release by acetylcholine and sympathetic nerve stimulation were blocked. The rates of recovery of these responses were similar with a half-time of 4 to 5 min. Although the antidromic response to KCl was blocked during the nicotine infusion, it recovered more rapidly. Within 1-1.5 min, the antidromic response to KCl tended to exceed control levels. It is proposed that nicotine causes a prolonged depolarization of the membrane of the adrenergic nerve terminal. The site of action of nicotine, the basis of its prolonged action, and the interrelationship of this depolarization with transmitter release and intracellular uptake are discussed.", "contents": "Electrical events associated with the action of nicotine at the adrenergic nerve terminal. Nicotine perfused through the coronary circulation of the isolated atropinized cat heart elicits antidromic activity in the cardiac sympathetic nerves. The pattern of discharge varies in a complex fashion with dose. At low concentrations, activity may last up to 10 min, whereas at high doses the antidromic response may last only a few seconds. Sympathetic transmitter is released into the perfusion fluid. There is dissociation between the amount of transmitter that overflows from the heart and the total antidromic activity with increasing dose of nicotine. With smaller doses of nicotine, the magnitude of the antidromic activity probably indicates the level of depolarization of the nerve terminal. Injection of greater doses of nicotine causes still greater transmitter release but not the generation of antidromic impulses, due presumably to persistent depolarization below a critical level. During the nicotine infusion and immediately afterwards, the antidromic response to acetylcholine and the effector responses associated with the adrenergic transmitter release by acetylcholine and sympathetic nerve stimulation were blocked. The rates of recovery of these responses were similar with a half-time of 4 to 5 min. Although the antidromic response to KCl was blocked during the nicotine infusion, it recovered more rapidly. Within 1-1.5 min, the antidromic response to KCl tended to exceed control levels. It is proposed that nicotine causes a prolonged depolarization of the membrane of the adrenergic nerve terminal. The site of action of nicotine, the basis of its prolonged action, and the interrelationship of this depolarization with transmitter release and intracellular uptake are discussed."}
{"id": "PMID:2125", "title": "Positive inotropic effect of insulin on rabbit auricle in vitro.", "content": "Water soluble pig insulin (4 x 10(-8) to 4 x 10(-7) g/ml) produced a marked and long-lasting increase in the contractile force of the rabbit auricle in vitro. Once the maximum effect for a given insulin concentration had been reached, addition of more insulin did not produce any further increase in inotropic effect. Insulin was without effect in reserpinized animals. Inhibition of cardiac beta-receptors by propranolol suppressed the positive inotropic effect of insulin. These findings support the hypothesis that insulin releases catecholamines from the myocardium.", "contents": "Positive inotropic effect of insulin on rabbit auricle in vitro. Water soluble pig insulin (4 x 10(-8) to 4 x 10(-7) g/ml) produced a marked and long-lasting increase in the contractile force of the rabbit auricle in vitro. Once the maximum effect for a given insulin concentration had been reached, addition of more insulin did not produce any further increase in inotropic effect. Insulin was without effect in reserpinized animals. Inhibition of cardiac beta-receptors by propranolol suppressed the positive inotropic effect of insulin. These findings support the hypothesis that insulin releases catecholamines from the myocardium."}
{"id": "PMID:2126", "title": "Ionic basis for intracellular 14C-nicotine accumulation in slices from different rat brain areas.", "content": "The effects of ionic alterations on the accumulation, distribution and movements of 14C-nicotine in slices from rat brain striatum, hypothalamus, cortex and cerebellum were studied. The uptake of 14C-nicotone is not dependent upon Na+ present in the incubation fluid because a K+-substituted (O-Na+) solution increased the 14C-nicotine tissue space, a tris-substituted (O-Na+) solution decreased the 14C-nicotine tissue space and a sucrose-substituted (O-Na+) solution did not change the amount of 14C-nicotine taken up when compared to the 14C-nicotine tissue space obtained in a normal incubation solution. However, all three Na+-free solutions elicited a sustained decrease in 14C-nicotine efflux. The increase in 14C-nicotine space produced in a K+-substituted (O-Na+) solution was present primarily in the slower component of a two-component washout, whereas the decrease produced in a tris-substituted (O-Na+) solution produced an equal percentage decrease in the size of both components. Most of the observed effects could be attributed to a linear relationship between the logarithm of the intracellular K+ concentration and the 14C-nicotine tissue space. In conclusion, it appears that there is an intracellular binding site for nicotine and that the degree of binding is dependent upon the concentration of K+.", "contents": "Ionic basis for intracellular 14C-nicotine accumulation in slices from different rat brain areas. The effects of ionic alterations on the accumulation, distribution and movements of 14C-nicotine in slices from rat brain striatum, hypothalamus, cortex and cerebellum were studied. The uptake of 14C-nicotone is not dependent upon Na+ present in the incubation fluid because a K+-substituted (O-Na+) solution increased the 14C-nicotine tissue space, a tris-substituted (O-Na+) solution decreased the 14C-nicotine tissue space and a sucrose-substituted (O-Na+) solution did not change the amount of 14C-nicotine taken up when compared to the 14C-nicotine tissue space obtained in a normal incubation solution. However, all three Na+-free solutions elicited a sustained decrease in 14C-nicotine efflux. The increase in 14C-nicotine space produced in a K+-substituted (O-Na+) solution was present primarily in the slower component of a two-component washout, whereas the decrease produced in a tris-substituted (O-Na+) solution produced an equal percentage decrease in the size of both components. Most of the observed effects could be attributed to a linear relationship between the logarithm of the intracellular K+ concentration and the 14C-nicotine tissue space. In conclusion, it appears that there is an intracellular binding site for nicotine and that the degree of binding is dependent upon the concentration of K+."}
{"id": "PMID:2127", "title": "Mechanism of the antidiuretic effect of beta-adrenergic stimulation in man.", "content": "Beta-Adrenergic stimulation with isoproterenol hydrochloride in animals causes an antidiuresis similar to antidiuretic hormone. This investigation was undertaken to determine whether isoproterenol inhibits water diuresis in man. Seven young male volunteers were studied during water diuresis in three phases: (1) water-loading, (2) water-loading plus isoproterenol, and (3) water-loading plus isoproterenol plus propranolol hydrochloride. Antidiuresis occurred 20 minutes following isoproterenol infusion (0.03mug to 0.06mug/kg/min) from a mean of 19.4 to 2.0 ml/min. We found that antidiuresis is due to the hormonal (antidiuretic hormone) and nonhormonal changes (decreased glomerular filtration rate and renal plasma flow). These in turn are due to the cardiovascular effects of the drug.", "contents": "Mechanism of the antidiuretic effect of beta-adrenergic stimulation in man. Beta-Adrenergic stimulation with isoproterenol hydrochloride in animals causes an antidiuresis similar to antidiuretic hormone. This investigation was undertaken to determine whether isoproterenol inhibits water diuresis in man. Seven young male volunteers were studied during water diuresis in three phases: (1) water-loading, (2) water-loading plus isoproterenol, and (3) water-loading plus isoproterenol plus propranolol hydrochloride. Antidiuresis occurred 20 minutes following isoproterenol infusion (0.03mug to 0.06mug/kg/min) from a mean of 19.4 to 2.0 ml/min. We found that antidiuresis is due to the hormonal (antidiuretic hormone) and nonhormonal changes (decreased glomerular filtration rate and renal plasma flow). These in turn are due to the cardiovascular effects of the drug."}
{"id": "PMID:2128", "title": "Renal acidification in sickle cell trait.", "content": "Nine sickle cell trait and nine control subjects underwent six-hour ammonium chloride acid loading. Maximal urine osmolality and renal hemodynamics were studied separately. Base line arterial pH, carbon dioxide pressure (Pco2), and [HCO3] were normal and comparable in the two groups. After ammonium chloride loading, urine pH decreased to 5.3 or less in all, and maximal excretion of ammonium and titratable and net acid was comparable as was urine minus blood Pco2 after bicarbonate loading. The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4, sickling, or adverse effects. Control and sickle cell trait subjects had comparable renal hemodynamics but maximal urine osmolality was lower in sickle-cell trait subjects. Adults with sickle cell trait have diminished renal concentrating ability and normal renal acidification and hemodynamics.", "contents": "Renal acidification in sickle cell trait. Nine sickle cell trait and nine control subjects underwent six-hour ammonium chloride acid loading. Maximal urine osmolality and renal hemodynamics were studied separately. Base line arterial pH, carbon dioxide pressure (Pco2), and [HCO3] were normal and comparable in the two groups. After ammonium chloride loading, urine pH decreased to 5.3 or less in all, and maximal excretion of ammonium and titratable and net acid was comparable as was urine minus blood Pco2 after bicarbonate loading. The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4, sickling, or adverse effects. Control and sickle cell trait subjects had comparable renal hemodynamics but maximal urine osmolality was lower in sickle-cell trait subjects. Adults with sickle cell trait have diminished renal concentrating ability and normal renal acidification and hemodynamics."}
{"id": "PMID:2129", "title": "Therapeutic implications of gentamicin accumulation in severly diseased kidneys.", "content": "We evaluated the influence of severe disease in human kidneys (12 patients) on gentamicin sulfate accumulation characteristics in such tissue and compared the results with intrarenal tissue concentration data derived from the study of healthy dogs (54 kidneys) during variation in hydration and urinary pH. Our results indicate that, in the management of pyelonephritis complicating preexisting renal disease, if the minimal inhibitory gentamicin concentration for an infecting organism is greater than the usual therapeutic an nontoxic serum levels of the compound, then it may be appropriate to use alternate antibiotics that demonstrate lesser reduction in tissue drug accumulation in diseased kidneys.", "contents": "Therapeutic implications of gentamicin accumulation in severly diseased kidneys. We evaluated the influence of severe disease in human kidneys (12 patients) on gentamicin sulfate accumulation characteristics in such tissue and compared the results with intrarenal tissue concentration data derived from the study of healthy dogs (54 kidneys) during variation in hydration and urinary pH. Our results indicate that, in the management of pyelonephritis complicating preexisting renal disease, if the minimal inhibitory gentamicin concentration for an infecting organism is greater than the usual therapeutic an nontoxic serum levels of the compound, then it may be appropriate to use alternate antibiotics that demonstrate lesser reduction in tissue drug accumulation in diseased kidneys."}
{"id": "PMID:2142", "title": "The influence of pH on the growth and stability of transmissible gastroenteritis virus in vitro.", "content": "The influence of pH on the growth of transmissible gastroenteritis virus (TGEV) in adult pig thyroid cell culture, and on the stability of the virus was studied. At pH 7.2 and 100 fold higher than those at pH 8.0. The adsorption, penetration and uncoating steps of the viral replicative cycle were shown to be unaffected by pH variation. Synthesis of TGEV RNA during the first 12 hours post infection was found to be unaffected by pH variation between the range 6.5-8.0. After 12 hours breakdown of this RNA appeared to occur in cultures held at pH 7.2 and 8.0 but not at pH 6.5. When incubated at 37 degrees C for 24 hours the virus infectivity was found to be least affected by pH 6.5 but when kept at 4 degrees C for the same length of time, the virus infectivity remained constant between pH 5.0 and pH 8.0.", "contents": "The influence of pH on the growth and stability of transmissible gastroenteritis virus in vitro. The influence of pH on the growth of transmissible gastroenteritis virus (TGEV) in adult pig thyroid cell culture, and on the stability of the virus was studied. At pH 7.2 and 100 fold higher than those at pH 8.0. The adsorption, penetration and uncoating steps of the viral replicative cycle were shown to be unaffected by pH variation. Synthesis of TGEV RNA during the first 12 hours post infection was found to be unaffected by pH variation between the range 6.5-8.0. After 12 hours breakdown of this RNA appeared to occur in cultures held at pH 7.2 and 8.0 but not at pH 6.5. When incubated at 37 degrees C for 24 hours the virus infectivity was found to be least affected by pH 6.5 but when kept at 4 degrees C for the same length of time, the virus infectivity remained constant between pH 5.0 and pH 8.0."}
{"id": "PMID:2143", "title": "The influence of physicochemical factors on the thermal inactivation of murine interferon.", "content": "The degradation of biological activity of virus-induced murine interferon was determined in linear nonisothermal and multiple isothermal tests. The stabilizing effect of pH during heating on interferon in solution was greatest at low pH, such that pH 2 greater than pH 5 greater than pH 7 greater than or equal to pH 9; freeze-dried preparations of interferon were also more heat-stable at acid pH than at neutral pH. Heat stability was a function of the H+-ion concentration rather than the ionic composition of the buffer; interferon solutions containing monovalent cations with different ionic radii had similar heat stability. A change in the H+ ion concentration was a critical event during the cooling of heated interferon: a shift in the direction of acidity contributed to stability whereas a shift towards alkalinity led to inactivation. The rate of cooling of heated interferon significantly influenced its residual activity. Rapid cooling and sudden freezing decreased the residual activities of interferons at pH 2 and 9 more than \"normal\" cooling, an effect not observed at pH 7. Interferon heated to 80degree C could not be reactivated at 40degree C or 55degree C. Interferon of higher apparent molecular weight was more heat-stable than that with lower apparent molecular weight. It is postulated that the physicochemical alterations in the aqueous environment significantly affecting the stability of interferon operate by producing changes in the size and/or conformation of interferon molecules. A model is proposed that relates thermal inactivation to different possible molecular states of interferon.", "contents": "The influence of physicochemical factors on the thermal inactivation of murine interferon. The degradation of biological activity of virus-induced murine interferon was determined in linear nonisothermal and multiple isothermal tests. The stabilizing effect of pH during heating on interferon in solution was greatest at low pH, such that pH 2 greater than pH 5 greater than pH 7 greater than or equal to pH 9; freeze-dried preparations of interferon were also more heat-stable at acid pH than at neutral pH. Heat stability was a function of the H+-ion concentration rather than the ionic composition of the buffer; interferon solutions containing monovalent cations with different ionic radii had similar heat stability. A change in the H+ ion concentration was a critical event during the cooling of heated interferon: a shift in the direction of acidity contributed to stability whereas a shift towards alkalinity led to inactivation. The rate of cooling of heated interferon significantly influenced its residual activity. Rapid cooling and sudden freezing decreased the residual activities of interferons at pH 2 and 9 more than \"normal\" cooling, an effect not observed at pH 7. Interferon heated to 80degree C could not be reactivated at 40degree C or 55degree C. Interferon of higher apparent molecular weight was more heat-stable than that with lower apparent molecular weight. It is postulated that the physicochemical alterations in the aqueous environment significantly affecting the stability of interferon operate by producing changes in the size and/or conformation of interferon molecules. A model is proposed that relates thermal inactivation to different possible molecular states of interferon."}
{"id": "PMID:2144", "title": "Isoelectric focusing of herpes simplex virus.", "content": "Herpes simplex virus was inserted into a preformed stable pH gradient and electrofocused for about one hour. Dextran was used as the density gradient forming agent. Virions banded at pH 4.9+/-0.1 and nucleocapsids at 4.1+/-0.05. About 10-20 per cent of infective virus was recovered.", "contents": "Isoelectric focusing of herpes simplex virus. Herpes simplex virus was inserted into a preformed stable pH gradient and electrofocused for about one hour. Dextran was used as the density gradient forming agent. Virions banded at pH 4.9+/-0.1 and nucleocapsids at 4.1+/-0.05. About 10-20 per cent of infective virus was recovered."}
{"id": "PMID:2145", "title": "Effect of pH on the growth and cytopathogenicity of avian infectious bronchitis virus in chick kidney cells.", "content": "The growth of avian infectious bronchitis virus (IBV) in chick kidney cells at different pH values in the range 6.0-9.0 demonstrated that although the virus was released at a much faster rate at the higher pH values the titre tended to drop more quickly. At the acid pH values the virus was released more slowly but reached a maximum titre similar to that at the higher pH values and showed only minimum reduction in infectivity up to 49 hours post inoculation. The stability of virus in tissue culture medium was shown to be directly related to pH 6.0-8.0, being more stable at the acid pH values. The degree of cytopathogenicity induced in chick kidney cells following infection with IBV was directly related to the pH at which the cells were incubated, occurring earlier and more extensively in cells at the higher pH values. Cell macromolecule synthesis in chick kidney cells was inhibited following infection with IBV and was apparently due to cell damage and death.", "contents": "Effect of pH on the growth and cytopathogenicity of avian infectious bronchitis virus in chick kidney cells. The growth of avian infectious bronchitis virus (IBV) in chick kidney cells at different pH values in the range 6.0-9.0 demonstrated that although the virus was released at a much faster rate at the higher pH values the titre tended to drop more quickly. At the acid pH values the virus was released more slowly but reached a maximum titre similar to that at the higher pH values and showed only minimum reduction in infectivity up to 49 hours post inoculation. The stability of virus in tissue culture medium was shown to be directly related to pH 6.0-8.0, being more stable at the acid pH values. The degree of cytopathogenicity induced in chick kidney cells following infection with IBV was directly related to the pH at which the cells were incubated, occurring earlier and more extensively in cells at the higher pH values. Cell macromolecule synthesis in chick kidney cells was inhibited following infection with IBV and was apparently due to cell damage and death."}
{"id": "PMID:2147", "title": "Eugenol improvement due to aging. A laboratory appraisal.", "content": "The characteristics of eugenol for dental use appear to improve with age. Exposure to air and light causes certain chemical and physical changes, but the exact nature of the age improvement requires further elucidation.", "contents": "Eugenol improvement due to aging. A laboratory appraisal. The characteristics of eugenol for dental use appear to improve with age. Exposure to air and light causes certain chemical and physical changes, but the exact nature of the age improvement requires further elucidation."}
{"id": "PMID:2149", "title": "Effect of prednisolone and salicyclic acid on ionic fluxes across the human stomach.", "content": "We compared ionic fluxes across human gastric mucosa after instillation of test solutions of isotonic hydrochloric acid alone or containing salicylic acid, or prednisolone or both. Prednisolone produced no alteration in fluxes of H+ and Na+ ions compared with controls. Salicyclic acid induced a significant net loss of H+ ions and gain of Na+ ions indicating alteration of the gastric mucosal barrier. Combined salicyclic acid plus prednisolone produced no increase in permeability of gastric mucosa to H+ and Na+ ions or to salicylic acid itself. Prednisolone was not appreciably absorbed from the stomach while salicylic acid was well absorbed. Combination of salicylic acid and prednisolone did not increase absorption of either drug. Neither salicylic acid nor prednisolone solutions alone or combined caused an increase in pepsin output over that due to 160 mM HCl. Salicylic acid resulted in a significant fall in potential difference compared to control while prednisolone produced no change in the one subject studied. In acute studies in man prednisolone is not absorbed from the stomach, does not itself affect the gastric mucosal barrier nor pepsin output nor does it enhance the absorption of or effect of salicylic acid on gastric ionic fluxes or pepsin output.", "contents": "Effect of prednisolone and salicyclic acid on ionic fluxes across the human stomach. We compared ionic fluxes across human gastric mucosa after instillation of test solutions of isotonic hydrochloric acid alone or containing salicylic acid, or prednisolone or both. Prednisolone produced no alteration in fluxes of H+ and Na+ ions compared with controls. Salicyclic acid induced a significant net loss of H+ ions and gain of Na+ ions indicating alteration of the gastric mucosal barrier. Combined salicyclic acid plus prednisolone produced no increase in permeability of gastric mucosa to H+ and Na+ ions or to salicylic acid itself. Prednisolone was not appreciably absorbed from the stomach while salicylic acid was well absorbed. Combination of salicylic acid and prednisolone did not increase absorption of either drug. Neither salicylic acid nor prednisolone solutions alone or combined caused an increase in pepsin output over that due to 160 mM HCl. Salicylic acid resulted in a significant fall in potential difference compared to control while prednisolone produced no change in the one subject studied. In acute studies in man prednisolone is not absorbed from the stomach, does not itself affect the gastric mucosal barrier nor pepsin output nor does it enhance the absorption of or effect of salicylic acid on gastric ionic fluxes or pepsin output."}
{"id": "PMID:2152", "title": "Effects of altering monoamine metabolism on the adrenocortical response to hypoxia.", "content": "Anesthetized dogs, which had been prepared with lumboadrenal vein cannulae, were intravenously infused with monoamine axidase (alphaETA), tryptophan hydroxylase (pCPA) or tyrosine hydroxylase (alphaMT) inhibitors 30 min prior to exposure to 10% oxygen at ground level. These studies were designed to ascertain the role of the neurotransmitters, serotonin and norepinephrine, in the adrenocortical response to hypoxia. In normoxic animals, alphaETA decreased basal cortisol secretion and increased systolic pressure, whereas pCPA and alphaMT were essentially without afffect on these parameters. All inhibitors prevented the rise in cortisol secretion usually observed in hypoxic dogs. Alpha ETA appeared to inhibit the adrenocortical response to hypoxia as a result of its potent pressore activity, while pCPA and alphaMT inhibited cortisol secretion by interfering with the synthesis of serotonin and norepinephrine, respictively. These data suggest that substances which alter the content and/or turnover of brain monoamines abolish the hypoxic rise in cortisol secretion and thus would lower the resistance of the animal to this stressor.", "contents": "Effects of altering monoamine metabolism on the adrenocortical response to hypoxia. Anesthetized dogs, which had been prepared with lumboadrenal vein cannulae, were intravenously infused with monoamine axidase (alphaETA), tryptophan hydroxylase (pCPA) or tyrosine hydroxylase (alphaMT) inhibitors 30 min prior to exposure to 10% oxygen at ground level. These studies were designed to ascertain the role of the neurotransmitters, serotonin and norepinephrine, in the adrenocortical response to hypoxia. In normoxic animals, alphaETA decreased basal cortisol secretion and increased systolic pressure, whereas pCPA and alphaMT were essentially without afffect on these parameters. All inhibitors prevented the rise in cortisol secretion usually observed in hypoxic dogs. Alpha ETA appeared to inhibit the adrenocortical response to hypoxia as a result of its potent pressore activity, while pCPA and alphaMT inhibited cortisol secretion by interfering with the synthesis of serotonin and norepinephrine, respictively. These data suggest that substances which alter the content and/or turnover of brain monoamines abolish the hypoxic rise in cortisol secretion and thus would lower the resistance of the animal to this stressor."}
{"id": "PMID:2153", "title": "Calcitonin-sensitive adenylate cyclase in rat renal tubular membranes.", "content": "1. Renal tubular membranes from rat kidneys were prepared, and adenylate cyclase activity was measured under basal conditions, after stimulation by NaF or salmon calcitonin. Apparent Km value of the enzyme for hormone-linked receptor was close to 1 x 10(-8) M. 2. The system was sensitive to temperature and pH. pH was found to act both on affinity for salmon calcitonin-linked receptor and maximum stimulation, suggesting an effect of pH on hormone-receptor binding and on a subsequent step. 3. KCl was without effect areas whereas CoCl and CaCl2 above 100 muM and MnCl2 above 1 muM inhibited F- -and salmon calcitonin-sensitive adenylate cyclase activities. The Ca2+ inhibition of the response reflected a fall in maximum stimulation and not a loss of affinity of salmon calcitonin-linked receptor for the enzyme. 4. The measurement of salmon calcitonin-sensitive adenylate cyclase activity as a function of ATP concentration showed that the hormone increases the maximum velocity of the adenylate cyclase. GTP, ITP and XTP at 200 muM did not modify basal, salmon calcitonin- and parathyroid hormone-sensitive adenylate cyclase activities. 5. Basal, salmon calcitonin- and F- -sensitive adenylate cyclase activities decreased at Mg2+ concentrations below 10 mM. High concentrations of Mg2+ (100 mM) led to an inhibition of the F- -stimulated enzyme. 6. Salmon calcitonin-linked receptor had a greater affinity for adenylate cyclase than human or porcine calcitonin-linked receptors. There was no additive effect of these three calcitonin peptides whereas parathyroid hormone added to salmon calcitonin increased adenylate cyclase activity, thus showing that both hormones bound to different membrane receptors. Human calcitonin fragments had no effect on adenylate cyclase activity. 7. Salmon calcitonin-stimulated adenylate cyclase activity decreased with the preincubation time. This was due to progressive degradation of the hormone and not to the rate of binding to membrane receptors.", "contents": "Calcitonin-sensitive adenylate cyclase in rat renal tubular membranes. 1. Renal tubular membranes from rat kidneys were prepared, and adenylate cyclase activity was measured under basal conditions, after stimulation by NaF or salmon calcitonin. Apparent Km value of the enzyme for hormone-linked receptor was close to 1 x 10(-8) M. 2. The system was sensitive to temperature and pH. pH was found to act both on affinity for salmon calcitonin-linked receptor and maximum stimulation, suggesting an effect of pH on hormone-receptor binding and on a subsequent step. 3. KCl was without effect areas whereas CoCl and CaCl2 above 100 muM and MnCl2 above 1 muM inhibited F- -and salmon calcitonin-sensitive adenylate cyclase activities. The Ca2+ inhibition of the response reflected a fall in maximum stimulation and not a loss of affinity of salmon calcitonin-linked receptor for the enzyme. 4. The measurement of salmon calcitonin-sensitive adenylate cyclase activity as a function of ATP concentration showed that the hormone increases the maximum velocity of the adenylate cyclase. GTP, ITP and XTP at 200 muM did not modify basal, salmon calcitonin- and parathyroid hormone-sensitive adenylate cyclase activities. 5. Basal, salmon calcitonin- and F- -sensitive adenylate cyclase activities decreased at Mg2+ concentrations below 10 mM. High concentrations of Mg2+ (100 mM) led to an inhibition of the F- -stimulated enzyme. 6. Salmon calcitonin-linked receptor had a greater affinity for adenylate cyclase than human or porcine calcitonin-linked receptors. There was no additive effect of these three calcitonin peptides whereas parathyroid hormone added to salmon calcitonin increased adenylate cyclase activity, thus showing that both hormones bound to different membrane receptors. Human calcitonin fragments had no effect on adenylate cyclase activity. 7. Salmon calcitonin-stimulated adenylate cyclase activity decreased with the preincubation time. This was due to progressive degradation of the hormone and not to the rate of binding to membrane receptors."}
{"id": "PMID:2154", "title": "Stabilization of rat liver tyrosine aminotransferase by tetracycline.", "content": "Rat liver tyrosine aminotransferase was purified 200-fold and an antiserum raised against it in rabbits. 2. Hepatic tyrosine aminotransferase activity was increased fourfold by tyrosine, twofold by tetracycline, 2.5-fold by cortisone 21-acetate and ninefold by a combination of tyrosine and cortisol administered intraperitoneally to rats. 3. Radioimmunoassay with 14C-labelled tyrosine aminotransferase, in conjunction with rabbit antiserum against the enzyme, revealed that cortisol stimulates the synthesis of the enzyme de novo, but that tetracycline has no such effect. 4. Incubation of rat liver homogenates with purified tyrosine aminotransferase in vitro leads to a rapid inactivation of the enzyme, which tetracycline partially inhibits. 5. The inactivation is brought about by intact lysosomes, and the addition of 10mM-cysteine increases the rate of enzyme inactivation, which is further markedly increased by 10mM-Mg2+ and 10mM-ATP. Here again tetracycline partially inhibits the decay rate, leading to the inference that the increase of tyrosine aminotransferase activity in vivo by tetracycline is brought about by the latter inhibiting the lysosomal catheptic action.", "contents": "Stabilization of rat liver tyrosine aminotransferase by tetracycline. Rat liver tyrosine aminotransferase was purified 200-fold and an antiserum raised against it in rabbits. 2. Hepatic tyrosine aminotransferase activity was increased fourfold by tyrosine, twofold by tetracycline, 2.5-fold by cortisone 21-acetate and ninefold by a combination of tyrosine and cortisol administered intraperitoneally to rats. 3. Radioimmunoassay with 14C-labelled tyrosine aminotransferase, in conjunction with rabbit antiserum against the enzyme, revealed that cortisol stimulates the synthesis of the enzyme de novo, but that tetracycline has no such effect. 4. Incubation of rat liver homogenates with purified tyrosine aminotransferase in vitro leads to a rapid inactivation of the enzyme, which tetracycline partially inhibits. 5. The inactivation is brought about by intact lysosomes, and the addition of 10mM-cysteine increases the rate of enzyme inactivation, which is further markedly increased by 10mM-Mg2+ and 10mM-ATP. Here again tetracycline partially inhibits the decay rate, leading to the inference that the increase of tyrosine aminotransferase activity in vivo by tetracycline is brought about by the latter inhibiting the lysosomal catheptic action."}
{"id": "PMID:2155", "title": "Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine.", "content": "1. Factors regulating the release of alanine and glutamine in vivo were investigated in starved rats by removing the liver from the circulation and monitoring blood metabolite changes for 30 min. 2. Alanine and glutamine were the predominant amino acids released into the circulation in this preparation. 3. Dichloroacetate, an activator of pyruvate dehydrogenase, inhibited net alanine release: it also interfered with the metabolism of the branched-chain amino acids valine, leucine and isoleucine. 4. L-Cycloserine, an inhibitor of alanine aminotransferase, decreased alanine accumulation by 80% after functional hepatectomy, whereas methionine sulphoximine, an inhibitor of glutamine synthetase, decreased glutamine accumulation by the same amount. 5. It was concluded that: (a) the alanine aminotransferase and the glutamine synthetase pathways respectively were responsible for 80% of the alanine and glutamine released into the circulation by the extrasplanchnic tissues, and extrahepatic proteolysis could account for a maximum of 20%; (b) alanine formation by the peripheral tissues was dependent on availability of pyruvate and not of glutamate; (c) glutamate availability could influence glutamine formation subject, possibly, to renal control.", "contents": "Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine. 1. Factors regulating the release of alanine and glutamine in vivo were investigated in starved rats by removing the liver from the circulation and monitoring blood metabolite changes for 30 min. 2. Alanine and glutamine were the predominant amino acids released into the circulation in this preparation. 3. Dichloroacetate, an activator of pyruvate dehydrogenase, inhibited net alanine release: it also interfered with the metabolism of the branched-chain amino acids valine, leucine and isoleucine. 4. L-Cycloserine, an inhibitor of alanine aminotransferase, decreased alanine accumulation by 80% after functional hepatectomy, whereas methionine sulphoximine, an inhibitor of glutamine synthetase, decreased glutamine accumulation by the same amount. 5. It was concluded that: (a) the alanine aminotransferase and the glutamine synthetase pathways respectively were responsible for 80% of the alanine and glutamine released into the circulation by the extrasplanchnic tissues, and extrahepatic proteolysis could account for a maximum of 20%; (b) alanine formation by the peripheral tissues was dependent on availability of pyruvate and not of glutamate; (c) glutamate availability could influence glutamine formation subject, possibly, to renal control."}
{"id": "PMID:2156", "title": "Amino acids attached to transfer ribonucleic acid in vivo.", "content": "1. tRNA was extracted from rabbit liver by both the phenol and diethyl pyrocarbonate methods under conditions preventing deacylation of the amino acids attached in vivo. 2. After deacylation 12 amino acids were determined by gas-liquid chromatography, by using the flame-ionization and nitrogen-sensitive thermionic detectors. 3. Comparison of the distribution of 12 amino acids attached to tRNA with those contained in total tissue protein and in the free pool showed little correlation. 4. Results for the enzymic charging assay for tRNA in vitro did not correlate satisfactorily with the analysis of amino acids attached to tRNA in vivo. Marked differences were ntoed in comparison made between our own and other published results.", "contents": "Amino acids attached to transfer ribonucleic acid in vivo. 1. tRNA was extracted from rabbit liver by both the phenol and diethyl pyrocarbonate methods under conditions preventing deacylation of the amino acids attached in vivo. 2. After deacylation 12 amino acids were determined by gas-liquid chromatography, by using the flame-ionization and nitrogen-sensitive thermionic detectors. 3. Comparison of the distribution of 12 amino acids attached to tRNA with those contained in total tissue protein and in the free pool showed little correlation. 4. Results for the enzymic charging assay for tRNA in vitro did not correlate satisfactorily with the analysis of amino acids attached to tRNA in vivo. Marked differences were ntoed in comparison made between our own and other published results."}
{"id": "PMID:2157", "title": "Initial rates of pyruvate transport in mitochondria determined by an \"inhibitor-stop\" technique.", "content": "An \"inhibitor-stop\" technique has been developed for measuring initial rates of pyruvate transport into mitochondria. The technique uses alpha-cyano-3-hydroxycinnamate as the inhibitor and separates the mitochondria from the radioactive medium by Millipore filtration. Observed rates depend on availability of hydroxyl and other exchangeable anions within the mitochondrial matrix.", "contents": "Initial rates of pyruvate transport in mitochondria determined by an \"inhibitor-stop\" technique. An \"inhibitor-stop\" technique has been developed for measuring initial rates of pyruvate transport into mitochondria. The technique uses alpha-cyano-3-hydroxycinnamate as the inhibitor and separates the mitochondria from the radioactive medium by Millipore filtration. Observed rates depend on availability of hydroxyl and other exchangeable anions within the mitochondrial matrix."}
{"id": "PMID:2158", "title": "A comparative study between a chondroitinase B and a chondroitinase AC from Flavobacterium heparinum: Isolation of a chondroitinase AC-susceptible dodecasaccharide from chondroitin sulphate B.", "content": "A chondroitinase that degrades only chondroitin sulphate B was isolated from Flavobacterium heparinum, and separated from a constitutive chondroitinase AC also present in extracts of F. heparinum. The enzyme acts only on chondroitin sulphate B, producing oligo- and tetra-saccharides, plus an unsaturated 4-sulphated disaccharide (deltaDi-4S). The oligosaccharide fraction (mol. wt. 3000) is susceptible to chondroitinase AC, producing mainly deltaDi-4S. The chondroitinase B is distinguished from chondroitinase AC by several properties, such as the effect of certain metal ions, temperature for optimal activity, and susceptibility to increasing salt concentrations. The enzyme is induced in F. heparinum by all the chondroitin sulphates, as well as by the disaccharides prepared from the chondroitins. The mechanism of induction of the enzyme and the structure of chondroitin sulphate B are discussed in relation to these results.", "contents": "A comparative study between a chondroitinase B and a chondroitinase AC from Flavobacterium heparinum: Isolation of a chondroitinase AC-susceptible dodecasaccharide from chondroitin sulphate B. A chondroitinase that degrades only chondroitin sulphate B was isolated from Flavobacterium heparinum, and separated from a constitutive chondroitinase AC also present in extracts of F. heparinum. The enzyme acts only on chondroitin sulphate B, producing oligo- and tetra-saccharides, plus an unsaturated 4-sulphated disaccharide (deltaDi-4S). The oligosaccharide fraction (mol. wt. 3000) is susceptible to chondroitinase AC, producing mainly deltaDi-4S. The chondroitinase B is distinguished from chondroitinase AC by several properties, such as the effect of certain metal ions, temperature for optimal activity, and susceptibility to increasing salt concentrations. The enzyme is induced in F. heparinum by all the chondroitin sulphates, as well as by the disaccharides prepared from the chondroitins. The mechanism of induction of the enzyme and the structure of chondroitin sulphate B are discussed in relation to these results."}
{"id": "PMID:2159", "title": "Subtilopeptidase A isoenzyme system. Interaction with serum components and its importance for quantitative immunoelectrophoresis.", "content": "A method was developed which involved electroimmunoassay and crossed immunoelectrophoresis of subtilopeptidase A (EC 3.4.21.14). Initial trials with unfractionated antiserum were not successful and interaction of the enzyme with non-immunoglobulin serum components were shown to be the cause of the failures. Quantitative immunoelectrophoresis was possible when purified immunoglobulins were used. A pH of 6.5 (lower than the usual pH 8.6) was necessary to obtain a proper baseline definition. Subtilopeptidase A was confirmed as a multiple isoenzyme system. Qualitative inter-batch variations were detected. Di-isopropyl phosphorofluoridate inhibition altered the electrophoretic pattern, but no loss of antigenic determinants was observed.", "contents": "Subtilopeptidase A isoenzyme system. Interaction with serum components and its importance for quantitative immunoelectrophoresis. A method was developed which involved electroimmunoassay and crossed immunoelectrophoresis of subtilopeptidase A (EC 3.4.21.14). Initial trials with unfractionated antiserum were not successful and interaction of the enzyme with non-immunoglobulin serum components were shown to be the cause of the failures. Quantitative immunoelectrophoresis was possible when purified immunoglobulins were used. A pH of 6.5 (lower than the usual pH 8.6) was necessary to obtain a proper baseline definition. Subtilopeptidase A was confirmed as a multiple isoenzyme system. Qualitative inter-batch variations were detected. Di-isopropyl phosphorofluoridate inhibition altered the electrophoretic pattern, but no loss of antigenic determinants was observed."}
{"id": "PMID:2160", "title": "Fructose 1,6-diphosphate aldolase from rabbit muscle. Effect of pH on the rate of formation and on the equilibrium concentration of the carbanion intermediate.", "content": "The rate of oxidation of ferricyanide of the aldolase-dihydroxyacetone phosphate complex was measured under different conditions. The following conclusions are drawn. 1. In the cleavage of fructose diphosphate, catalysed by native aldolase, the steady-state concentration of the enzyme-dihydroxyacetone phosphate carbanion intermediate represents less than 6% of the total enzyme-substrate intermediates. 2. Fructose diphosphate and dihydroxyacetone phosphate compete for the four catalytic sites on aldolase, the binding of fructose diphosphate being about twice as tight. 3. The equilibrium concentration of the carbanion intermediate formed by reaction of carboxypeptidase-treated aldolase with dihydroxyacetone phosphate is independent of pH between 5.0 and 9.0. The rates of fromation of the carbanion intermediate and of the reverse reaction are, however, concomitantly increased by increasing pH between 5.0 and 6.5.", "contents": "Fructose 1,6-diphosphate aldolase from rabbit muscle. Effect of pH on the rate of formation and on the equilibrium concentration of the carbanion intermediate. The rate of oxidation of ferricyanide of the aldolase-dihydroxyacetone phosphate complex was measured under different conditions. The following conclusions are drawn. 1. In the cleavage of fructose diphosphate, catalysed by native aldolase, the steady-state concentration of the enzyme-dihydroxyacetone phosphate carbanion intermediate represents less than 6% of the total enzyme-substrate intermediates. 2. Fructose diphosphate and dihydroxyacetone phosphate compete for the four catalytic sites on aldolase, the binding of fructose diphosphate being about twice as tight. 3. The equilibrium concentration of the carbanion intermediate formed by reaction of carboxypeptidase-treated aldolase with dihydroxyacetone phosphate is independent of pH between 5.0 and 9.0. The rates of fromation of the carbanion intermediate and of the reverse reaction are, however, concomitantly increased by increasing pH between 5.0 and 6.5."}
{"id": "PMID:2161", "title": "Purification and characterization of a collagenase extracted from rabbit tumours.", "content": "A collagenase was purified from homogenates of V2 ascites-cell carcinoma growing in rabbit muscle. (NH4)2SO4 precipitation, ion-exchange and gel-filtration chromatography, and affinity chromatography (by using the CB7 CNBr) cleavage fragment of alpha 1(I) collagen linked to agarose) gave a 268000-fold purification and a sevenfold increase in total enzyme units recovered. The specific activity, defined as mumol of collagen in solution cleaved/h per mg of enzyme at 35 degrees C, WAS 1.74.2. The collagenase had a broad pH optimum from pH7.0 to 9.5, and a mol.wt. of between 33000 and 35000. It was inhibited by dithiothreitol, L-cysteine, D-penicillamine, EDTA and 1,10-phenanthroline, and by both rabbit and human serum. 3. Removal of cations by a chelating resin (Chelex 100) produced as inactive enzyme that could be reactiviated by the addition of Ca2+ ions at concentrations as low as 1muM. Other bivalent cations were not effective. 4. The purified collagenase cleaved peptides alpha2 and alpha1-CB7 (denatured polypeptides of collagen) at 37 degrees C at one site only. [alpha1 (I)]2alpha2 and [alpha1(III)]3 collagens in solution were cleaved at the same site approximately five times more rapidly than [alpha1 (II)]3. 5. An inhibitor of the enzyme in the tumour extracts, which was dissociable from the enzyme at the (NH4) 2SO4 precipitation step of purification, had a mol. wt. of between 40000 and 50000 but was distinct from the alpha1 trypsin inhibitor. 6. Studies with zonal density-gradient centrifugation suggested that the enzyme was bound to fibrillar substrate (collagen) extracellularly, but that it was not associated with enzymes originating in cell mitochondria, microsomal preparations or lysosomes.", "contents": "Purification and characterization of a collagenase extracted from rabbit tumours. A collagenase was purified from homogenates of V2 ascites-cell carcinoma growing in rabbit muscle. (NH4)2SO4 precipitation, ion-exchange and gel-filtration chromatography, and affinity chromatography (by using the CB7 CNBr) cleavage fragment of alpha 1(I) collagen linked to agarose) gave a 268000-fold purification and a sevenfold increase in total enzyme units recovered. The specific activity, defined as mumol of collagen in solution cleaved/h per mg of enzyme at 35 degrees C, WAS 1.74.2. The collagenase had a broad pH optimum from pH7.0 to 9.5, and a mol.wt. of between 33000 and 35000. It was inhibited by dithiothreitol, L-cysteine, D-penicillamine, EDTA and 1,10-phenanthroline, and by both rabbit and human serum. 3. Removal of cations by a chelating resin (Chelex 100) produced as inactive enzyme that could be reactiviated by the addition of Ca2+ ions at concentrations as low as 1muM. Other bivalent cations were not effective. 4. The purified collagenase cleaved peptides alpha2 and alpha1-CB7 (denatured polypeptides of collagen) at 37 degrees C at one site only. [alpha1 (I)]2alpha2 and [alpha1(III)]3 collagens in solution were cleaved at the same site approximately five times more rapidly than [alpha1 (II)]3. 5. An inhibitor of the enzyme in the tumour extracts, which was dissociable from the enzyme at the (NH4) 2SO4 precipitation step of purification, had a mol. wt. of between 40000 and 50000 but was distinct from the alpha1 trypsin inhibitor. 6. Studies with zonal density-gradient centrifugation suggested that the enzyme was bound to fibrillar substrate (collagen) extracellularly, but that it was not associated with enzymes originating in cell mitochondria, microsomal preparations or lysosomes."}
{"id": "PMID:2162", "title": "Inhibition of leucocytic lysosomal enzymes by glycosaminoglycans in vitro.", "content": "1. A lysosomal fraction was separated by density-gradient centrifugation from a highly purified human polymorphonuclear leucocyte suspension. 2. Some 23 different lysosomal enzymes were assayed for activity in the presence of various concentrations of glycosaminoglycans. 3. The 21 acid hydrolases assayed were strongly inhibited to different degrees by low (0-12 mmol/l) concentrations of glycosaminoglycans in a pH-dependent manner. Thus inhibitions were stronger below pH4.5, with activity returning to control values at about pH5.0. 4. On a molar basis, the inhibitory activity for the several glycosaminoglycans studied was: heparin greater than chondroitin sulphate greater than hyaluronic acid. 5. Once the glycosaminoglycan-acid hydrolase complex was formed, it was partially dissociated by slight elevations in the pH of the incubation medium, by increasing the ionic strength of the incubation medium, or by adding several cationic proteins (e.g. histone, protamine). 6. As leucocytic lysosomes contain large amounts of chondroitin sulphate, and have a strongly acid intragranular pH, we suggest that glycosaminoglycans may modify lysosomal function through the formation of complexes with lysosomal enzymes, by inhibiting the digestive activity of the acid hydrolases when the intralysosomal pH is below their pI.", "contents": "Inhibition of leucocytic lysosomal enzymes by glycosaminoglycans in vitro. 1. A lysosomal fraction was separated by density-gradient centrifugation from a highly purified human polymorphonuclear leucocyte suspension. 2. Some 23 different lysosomal enzymes were assayed for activity in the presence of various concentrations of glycosaminoglycans. 3. The 21 acid hydrolases assayed were strongly inhibited to different degrees by low (0-12 mmol/l) concentrations of glycosaminoglycans in a pH-dependent manner. Thus inhibitions were stronger below pH4.5, with activity returning to control values at about pH5.0. 4. On a molar basis, the inhibitory activity for the several glycosaminoglycans studied was: heparin greater than chondroitin sulphate greater than hyaluronic acid. 5. Once the glycosaminoglycan-acid hydrolase complex was formed, it was partially dissociated by slight elevations in the pH of the incubation medium, by increasing the ionic strength of the incubation medium, or by adding several cationic proteins (e.g. histone, protamine). 6. As leucocytic lysosomes contain large amounts of chondroitin sulphate, and have a strongly acid intragranular pH, we suggest that glycosaminoglycans may modify lysosomal function through the formation of complexes with lysosomal enzymes, by inhibiting the digestive activity of the acid hydrolases when the intralysosomal pH is below their pI."}
{"id": "PMID:2274", "title": "Circulating levels of prolactin in human breast cancer.", "content": "Serum prolactin concentrations were measured by radioimmunoassays in 98 patients with established carcinoma of breast, 12 patients with cystic mastitis and 10 patients with gynaecomastia and compared with that of age matched normal control women. The serum prolactin levels in the patients with breast cancer, gynaecomastia or cystic mastitis were observed to be similar to that in normal women. It was interesting to note that the levels of prolactin in the luteal phase of the cycle were higher than that in the early follicular phase in normal women.", "contents": "Circulating levels of prolactin in human breast cancer. Serum prolactin concentrations were measured by radioimmunoassays in 98 patients with established carcinoma of breast, 12 patients with cystic mastitis and 10 patients with gynaecomastia and compared with that of age matched normal control women. The serum prolactin levels in the patients with breast cancer, gynaecomastia or cystic mastitis were observed to be similar to that in normal women. It was interesting to note that the levels of prolactin in the luteal phase of the cycle were higher than that in the early follicular phase in normal women."}
{"id": "PMID:2275", "title": "Effect of aflatoxin B1 on pyridine nucleotides and NADP linked dehydrogenases.", "content": "The effect of a single interaperitoneal injection (6 mg/kg body weight) of aflatoxin B1 in propylene glycol on pyridine nucleotides and NDP linked dehydrogenases was studied 24 h after administration of the toxin. The liver showed a decrease in total proteins and pyridine nucleotides though levels of NADP and NADPH remained unchanged. Levels of NAD and NADH were decreased. The activities of hepatic of hwpRIX of hepatic malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were not altered though ICDH showed an increase when expressed on protein basis. However, there was a significance decrease in the activity of combined HMP dehydrogenases. Adipose tissue showed increased activities of the HMP dehydrogenasess.", "contents": "Effect of aflatoxin B1 on pyridine nucleotides and NADP linked dehydrogenases. The effect of a single interaperitoneal injection (6 mg/kg body weight) of aflatoxin B1 in propylene glycol on pyridine nucleotides and NDP linked dehydrogenases was studied 24 h after administration of the toxin. The liver showed a decrease in total proteins and pyridine nucleotides though levels of NADP and NADPH remained unchanged. Levels of NAD and NADH were decreased. The activities of hepatic of hwpRIX of hepatic malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were not altered though ICDH showed an increase when expressed on protein basis. However, there was a significance decrease in the activity of combined HMP dehydrogenases. Adipose tissue showed increased activities of the HMP dehydrogenasess."}
{"id": "PMID:2276", "title": "Esterase activity of zinc neutral proteases.", "content": "The hydrolysis of a series of depsipeptides demonstrates that the zinc neutral endopeptidases of bacteria are active esterases. Esters such as BzGly-OPhe-Ala, BzGly-OLeu-Ala, and FA-Gly-OLeu-NH2 are hydrolyzed at rates three- to eightfold slower than are their exact peptide analogues, when hydrolyzed by thermolysin, Bacillus subtilis neutral protease and the neutral protease from Aeromonas proteolytica. Ester hydrolysis by zinc neutral proteases follows the characteristic preference for hydrophobic amino acids adjacent to the site of cleavage, discerned from the hydrolysis of peptide substrates. Removal of zinc from thermolysin abolishes the esterase activity of the native enzyme. Among the metals examined, only Co2+ and Zn2+ restore esterase activity to any significant extent, Co2+ restoring 50% and Zn2+ 100% of the native thermolysin activity. The hydrolysis of esters and peptides by thermolysin does not differ with respect to either the binding or catalytic steps. Substrate specificity, pH-rate profiles, inhibitor, and deuterium isotope effects are identical for both types of substrates.", "contents": "Esterase activity of zinc neutral proteases. The hydrolysis of a series of depsipeptides demonstrates that the zinc neutral endopeptidases of bacteria are active esterases. Esters such as BzGly-OPhe-Ala, BzGly-OLeu-Ala, and FA-Gly-OLeu-NH2 are hydrolyzed at rates three- to eightfold slower than are their exact peptide analogues, when hydrolyzed by thermolysin, Bacillus subtilis neutral protease and the neutral protease from Aeromonas proteolytica. Ester hydrolysis by zinc neutral proteases follows the characteristic preference for hydrophobic amino acids adjacent to the site of cleavage, discerned from the hydrolysis of peptide substrates. Removal of zinc from thermolysin abolishes the esterase activity of the native enzyme. Among the metals examined, only Co2+ and Zn2+ restore esterase activity to any significant extent, Co2+ restoring 50% and Zn2+ 100% of the native thermolysin activity. The hydrolysis of esters and peptides by thermolysin does not differ with respect to either the binding or catalytic steps. Substrate specificity, pH-rate profiles, inhibitor, and deuterium isotope effects are identical for both types of substrates."}
{"id": "PMID:2277", "title": "The binding of reduced nicotinamide adenine dinucleotide to citrate synthase of Escherichia coli K12.", "content": "Citrate synthase from Escherichia coli enhances the fluorescence of its allosteric inhibitor, NADH, and shifts the peak of emission of the coenzyme from 457 to 428 nm. These effects have been used to measure the binding of NADH to this enzyme under various conditions. The dissociation constant for the NADH-citrate synthase complex is about 0.28 muM at pH 6.2, but increases toward alkaline pH as if binding depends on protonation of a group with a pKa of about 7.05. Over the pH range 6.2-8.7, the number of binding sites decreases from about 0.65 to about 0.25 per citrate synthase subunit. The midpoint of this transition is at about pH 7.7, and it may be one reflection of the partial depolymerization of the enzyme which is known to occur in this pH range. A gel filtration method has been used to verify that the fluorescence enhancement technique accurately reveals all of the NADH molecules bound to the enzyme in the concentration range of interest. NAD+ and NADP+ were weak competitive inhibitors of NADH binding at pH 7.8 (Ki values greater than 1 mM), but stronger inhibition was shown by 5'-AMP and 3'-AMP, with Ki values of 83 +/- 5 and 65 +/- 4 muM, respectively. Acetyl-CoA, one of the substrates, and KCl, an activator, also inhibit the binding in a weakly cooperative manner. All of these effects are consistent with kinetic observations on this system. We interpret our results in terms of two types of binding site for nucleotides on citrate synthase: an active site which binds acetyl-CoA, the substrate, or its analogue 3'-AMP; and an allosteric site which binds NADH or its analogue 5'-AMP and has a lesser affinity for other nicotinamide adenine dinucloetides. When the active site is occupied, we propose that NADH cannot bind to the allosteric site, but 5'-AMP can; conversely, when NADH is the in the allosteric site, the active site cannot be occupied. In addition to these two classes of sites, there must be points for interaction with KCl and other salts. Oxaloacetate, the second substrate, and alpha-ketoglutarate, an inhibitor whose mode of action is believed to be allosteric, have no effect on NADH binding to citrate synthase at pH 7.8. When NADH is bound to citrate synthase, it quenches the intrinsic tryptophan fluorescence of the enzyme. The amount of quenching is proportional to the amount of NADH bound, at least up to a binding ratio of 0.50 NADH per enzyme subunit. This amount of binding leads to the quenching of 53 +/- 5% of the enzyme fluorescence, which means that one NADH molecule can quench all the intrinsic fluorescence of the subunit to which it binds.", "contents": "The binding of reduced nicotinamide adenine dinucleotide to citrate synthase of Escherichia coli K12. Citrate synthase from Escherichia coli enhances the fluorescence of its allosteric inhibitor, NADH, and shifts the peak of emission of the coenzyme from 457 to 428 nm. These effects have been used to measure the binding of NADH to this enzyme under various conditions. The dissociation constant for the NADH-citrate synthase complex is about 0.28 muM at pH 6.2, but increases toward alkaline pH as if binding depends on protonation of a group with a pKa of about 7.05. Over the pH range 6.2-8.7, the number of binding sites decreases from about 0.65 to about 0.25 per citrate synthase subunit. The midpoint of this transition is at about pH 7.7, and it may be one reflection of the partial depolymerization of the enzyme which is known to occur in this pH range. A gel filtration method has been used to verify that the fluorescence enhancement technique accurately reveals all of the NADH molecules bound to the enzyme in the concentration range of interest. NAD+ and NADP+ were weak competitive inhibitors of NADH binding at pH 7.8 (Ki values greater than 1 mM), but stronger inhibition was shown by 5'-AMP and 3'-AMP, with Ki values of 83 +/- 5 and 65 +/- 4 muM, respectively. Acetyl-CoA, one of the substrates, and KCl, an activator, also inhibit the binding in a weakly cooperative manner. All of these effects are consistent with kinetic observations on this system. We interpret our results in terms of two types of binding site for nucleotides on citrate synthase: an active site which binds acetyl-CoA, the substrate, or its analogue 3'-AMP; and an allosteric site which binds NADH or its analogue 5'-AMP and has a lesser affinity for other nicotinamide adenine dinucloetides. When the active site is occupied, we propose that NADH cannot bind to the allosteric site, but 5'-AMP can; conversely, when NADH is the in the allosteric site, the active site cannot be occupied. In addition to these two classes of sites, there must be points for interaction with KCl and other salts. Oxaloacetate, the second substrate, and alpha-ketoglutarate, an inhibitor whose mode of action is believed to be allosteric, have no effect on NADH binding to citrate synthase at pH 7.8. When NADH is bound to citrate synthase, it quenches the intrinsic tryptophan fluorescence of the enzyme. The amount of quenching is proportional to the amount of NADH bound, at least up to a binding ratio of 0.50 NADH per enzyme subunit. This amount of binding leads to the quenching of 53 +/- 5% of the enzyme fluorescence, which means that one NADH molecule can quench all the intrinsic fluorescence of the subunit to which it binds."}
{"id": "PMID:2278", "title": "The structure of the covalent adduct formed by the interaction of 3-dimethylamino-1-propyne and the flavine of mitochondrial amine oxidase.", "content": "3-Dimethylamino-1-propyne irreversibly inactivates mitochondrial monoamine oxidase from bovine liver. The inactivation results in the loss of absorption in the 450-500-nm region of the flavine spectrum and a concomitant increase in absorbance at 410 nm. For the enzyme-bound adduct epsilon410 = 28000. The spectral properties of the adduct of the liver enzyme with 3-dimethylamino-1-propyne are similar to those observed when the pig kidney enzyme is inactivated with pargyline (Chuang et al. (1974), J. Biol. Chem. 249, 2381). From a proteolytic digest of the enzyme inactivated with labeled inhibitor a flavine peptide has been isolated which contains 1 mol of inactivator/mol of flavine. The chemical and spectral properties of the adduct are those of compounds containing the structure --N--CH==CH--CH==N+ less than. It was concluded that the flavine-inhibtor adduct is a N-5 substituted dihydroflavine and its structure has been determined.", "contents": "The structure of the covalent adduct formed by the interaction of 3-dimethylamino-1-propyne and the flavine of mitochondrial amine oxidase. 3-Dimethylamino-1-propyne irreversibly inactivates mitochondrial monoamine oxidase from bovine liver. The inactivation results in the loss of absorption in the 450-500-nm region of the flavine spectrum and a concomitant increase in absorbance at 410 nm. For the enzyme-bound adduct epsilon410 = 28000. The spectral properties of the adduct of the liver enzyme with 3-dimethylamino-1-propyne are similar to those observed when the pig kidney enzyme is inactivated with pargyline (Chuang et al. (1974), J. Biol. Chem. 249, 2381). From a proteolytic digest of the enzyme inactivated with labeled inhibitor a flavine peptide has been isolated which contains 1 mol of inactivator/mol of flavine. The chemical and spectral properties of the adduct are those of compounds containing the structure --N--CH==CH--CH==N+ less than. It was concluded that the flavine-inhibtor adduct is a N-5 substituted dihydroflavine and its structure has been determined."}
{"id": "PMID:2279", "title": "The absolute configuration of the amino acids in delta-(alpha-aminoadipyl)cysteinylvaline from Penicillium chrysogenum.", "content": "Radioactive carbon-14 L-alpha-aminoadipic acid, L-cysteine, or L-valine were readily incorporated into the intracellular tripeptide, delta-(alpha-aminoadipyl)cysteinylvaline (ACV), by washed starved cells of Penicillium chrysogenum. The labeled ACV in each case was oxidized with performic acid and isolated as its corresponding sulfonic acid derivative. After acid hydrolysis, the configuration of the component acids was determined by L- and D-amino acid oxidases, which showed the tripeptide (ACV) from P. chrysogenum to be delta-(L-aminoadipyl)-L-cysteinyl-D-valine.", "contents": "The absolute configuration of the amino acids in delta-(alpha-aminoadipyl)cysteinylvaline from Penicillium chrysogenum. Radioactive carbon-14 L-alpha-aminoadipic acid, L-cysteine, or L-valine were readily incorporated into the intracellular tripeptide, delta-(alpha-aminoadipyl)cysteinylvaline (ACV), by washed starved cells of Penicillium chrysogenum. The labeled ACV in each case was oxidized with performic acid and isolated as its corresponding sulfonic acid derivative. After acid hydrolysis, the configuration of the component acids was determined by L- and D-amino acid oxidases, which showed the tripeptide (ACV) from P. chrysogenum to be delta-(L-aminoadipyl)-L-cysteinyl-D-valine."}
{"id": "PMID:2280", "title": "Chromatin-bound protease: degradation of chromosomal proteins under chromatin dissociation conditions.", "content": "A chromatin-bound protease, active in 2 M NaCl-5 M urea or 5 M urea alone, was demonstrated in rat liver, kidney, testes, brain, rabbit bone marrow, chicken reticulocyte, and Ehrlich ascites chromatin. Chicken erythrocyte chromatin did not possess any detectable proteolytic activity in salt and urea. The proteolytic activity of rat liver chromatin in salt and urea was found to be independent of the methods of chromatin preparation. The protease can be inhibited by the serine specific reagents phenylmethanesulfonyl fluoride and diisopropyl fluorophosphate and the alkylating reagent, carbobenzoxyphenylalanine chloromethyl ketone, in the presence of organic solvents at 1 mM concentration. The inhibitions of chromatin-bound protease in rat liver by these compounds are irreversible. On the other hand, carbobenzoxyphenylalanine and p-nitrophenyl acetate were shown to be reversible inhibitors of rat liver chromatin-bound protease. The application of these inhibitors during the dissociation of chromatin by salt and urea may be useful to researchers interested in purifying various chromosomal proteins or to those researchers doing reconstitution studies with labile chromatins.", "contents": "Chromatin-bound protease: degradation of chromosomal proteins under chromatin dissociation conditions. A chromatin-bound protease, active in 2 M NaCl-5 M urea or 5 M urea alone, was demonstrated in rat liver, kidney, testes, brain, rabbit bone marrow, chicken reticulocyte, and Ehrlich ascites chromatin. Chicken erythrocyte chromatin did not possess any detectable proteolytic activity in salt and urea. The proteolytic activity of rat liver chromatin in salt and urea was found to be independent of the methods of chromatin preparation. The protease can be inhibited by the serine specific reagents phenylmethanesulfonyl fluoride and diisopropyl fluorophosphate and the alkylating reagent, carbobenzoxyphenylalanine chloromethyl ketone, in the presence of organic solvents at 1 mM concentration. The inhibitions of chromatin-bound protease in rat liver by these compounds are irreversible. On the other hand, carbobenzoxyphenylalanine and p-nitrophenyl acetate were shown to be reversible inhibitors of rat liver chromatin-bound protease. The application of these inhibitors during the dissociation of chromatin by salt and urea may be useful to researchers interested in purifying various chromosomal proteins or to those researchers doing reconstitution studies with labile chromatins."}
{"id": "PMID:2281", "title": "ATPase of Escherichia coli: purification, dissociation, and reconstitution of the active complex from the isolated subunits.", "content": "A simple procedure for the purification of Mg2+-stimulated ATPase of Escherichia coli by fractionation with poly(ethylene glycols) and gel filtration is described. The enzyme restores ATPase-linked reactions to membrane preparations lacking these activities. Five different polypeptides (alpha, beta, gamma, delta, epsilon) are observed in sodium dodecyl sulfate electrophoresis. Freezing in salt solutions splits the enzyme complex into subunits which do not possess any catalytic activity. The presence of different subunits is confirmed by electrophoretic and immunological methods. The active enzyme complex can be reconstituted by decreasing the ionic strength in the dissociated sample. Temperature, pH, protein concentration, and the presence of substrate are each important determinants of the rate and extent of reconstitution. The dissociated enzyme has been separated by ion-exchange chromatography into two major fragments. Fragment IA has a molecular weight of about 100000 and contains the alpha, gamma, and epsilon polypeptides. The minor fragment, IB, has about the same molecular weight but contains, besides alpha, gamma, and epsilon, the delta polypeptide. Fragment II, with a molecular weight of about 52000, appears to be identical with the beta polypeptide. ATPase activity can be reconstituted from fragments IA and II, whereas the capacity of the ATPase to drive energy-dependent processes in depleted membrane vesicles is only restored after incubation of these two fractions with fraction IB, which contains the delta subunit.", "contents": "ATPase of Escherichia coli: purification, dissociation, and reconstitution of the active complex from the isolated subunits. A simple procedure for the purification of Mg2+-stimulated ATPase of Escherichia coli by fractionation with poly(ethylene glycols) and gel filtration is described. The enzyme restores ATPase-linked reactions to membrane preparations lacking these activities. Five different polypeptides (alpha, beta, gamma, delta, epsilon) are observed in sodium dodecyl sulfate electrophoresis. Freezing in salt solutions splits the enzyme complex into subunits which do not possess any catalytic activity. The presence of different subunits is confirmed by electrophoretic and immunological methods. The active enzyme complex can be reconstituted by decreasing the ionic strength in the dissociated sample. Temperature, pH, protein concentration, and the presence of substrate are each important determinants of the rate and extent of reconstitution. The dissociated enzyme has been separated by ion-exchange chromatography into two major fragments. Fragment IA has a molecular weight of about 100000 and contains the alpha, gamma, and epsilon polypeptides. The minor fragment, IB, has about the same molecular weight but contains, besides alpha, gamma, and epsilon, the delta polypeptide. Fragment II, with a molecular weight of about 52000, appears to be identical with the beta polypeptide. ATPase activity can be reconstituted from fragments IA and II, whereas the capacity of the ATPase to drive energy-dependent processes in depleted membrane vesicles is only restored after incubation of these two fractions with fraction IB, which contains the delta subunit."}
{"id": "PMID:2282", "title": "Conformation of gonadotropin releasing hormone.", "content": "The conformation of the gonadotropin releasing hormone (Gn-RH), whose primary sequence is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH2, and of several of its structural analogues has been studied by circular dichroism, optical rotatory dispersion, and fluorescence spectroscopy. The effects of pH, guanidine, and temperature on fluorescence emission have also been examined. Titration data demonstrate that the histidine and tyrosine residues are free of any mutual interactions. The similarity of emission spectra in water and in guanidine hydrochloride solutions precludes significant interactions between the fluorescent groups and other residues. Neither the temperature nor the pH profiles of the emission intensities of either tyrosine or tryptophan reveal any fixed secondary structure in Gn-RH. Both the extent of alkaline quenching and the distance of 10-11 A calculated from F\u00f6rster energy transfer theory are in accord with a randomly coiled structure with only one residue between tyrosine and tryptophan. Furthermore, the circular dichroism spectrum and optical rotatory dispersion do not exhibit any contributions from peptide bonds in an ordered structure, although there is a perturbation of the peptide absorption region due to overlapping bands from side-chain chromophores. Gn-RH, therefore, appears to behave as a random coil polypeptide in water devoid of any intrachain residue interactions. This nonordered structure in Gn-RH and the lack of any significant differences in the physical-chemical properties of the hormone analogues indicate that a predetermined solution conformation is not required for biological activity. In contrast to its behavior in water, Gn-RH in trifluoroethanol exhibits a conformational transition, with the formation of a beta structure. Differences in conformational changes exhibited by several analogues in trifluoroethanol may be relevant to their relative biological activities at the receptor site.", "contents": "Conformation of gonadotropin releasing hormone. The conformation of the gonadotropin releasing hormone (Gn-RH), whose primary sequence is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH2, and of several of its structural analogues has been studied by circular dichroism, optical rotatory dispersion, and fluorescence spectroscopy. The effects of pH, guanidine, and temperature on fluorescence emission have also been examined. Titration data demonstrate that the histidine and tyrosine residues are free of any mutual interactions. The similarity of emission spectra in water and in guanidine hydrochloride solutions precludes significant interactions between the fluorescent groups and other residues. Neither the temperature nor the pH profiles of the emission intensities of either tyrosine or tryptophan reveal any fixed secondary structure in Gn-RH. Both the extent of alkaline quenching and the distance of 10-11 A calculated from F\u00f6rster energy transfer theory are in accord with a randomly coiled structure with only one residue between tyrosine and tryptophan. Furthermore, the circular dichroism spectrum and optical rotatory dispersion do not exhibit any contributions from peptide bonds in an ordered structure, although there is a perturbation of the peptide absorption region due to overlapping bands from side-chain chromophores. Gn-RH, therefore, appears to behave as a random coil polypeptide in water devoid of any intrachain residue interactions. This nonordered structure in Gn-RH and the lack of any significant differences in the physical-chemical properties of the hormone analogues indicate that a predetermined solution conformation is not required for biological activity. In contrast to its behavior in water, Gn-RH in trifluoroethanol exhibits a conformational transition, with the formation of a beta structure. Differences in conformational changes exhibited by several analogues in trifluoroethanol may be relevant to their relative biological activities at the receptor site."}
{"id": "PMID:2284", "title": "Low and high pH form of cadmium carbonic anhydrase determined by nuclear quadrupole interaction.", "content": "The pH dependence of the nuclear quadrupole interaction between the excited 247-keV state in 111Cd bound to the active site in human carbonic anhydrase B and the nearest protein surroundings has been studied by means of the nuclear spectroscopic technique of perturbed angular correlation of gamma rays. The enzyme has been studied in the pH region 5.6-11.0 at 22 and -196 degrees C. The results show that the Cd enzyme changes from one form at low pH to another form at high pH both at 22 and -196 degrees C. The pK of the transition is 8.9 +/- 0.2 at -196 degrees C and close to 9 at 22 degrees C. Parallel to this transformation, the esterase activity of the Cd enzyme for the hydration of p-nitrophenyl acetate exhibits a pH dependency with a pH of 9.1 +/- 0.2. The sulfonamide inhibitor acetazolamide completely inhibits this activity of the Cd enzyme. The quadrupole interaction parameters for the Cd enzyme are not significantly different at -196 degrees C from those obtained at 22 degrees C. A measurement at 0 degrees C pH 5.7 shows, however, a form different from those at 22 degrees C pH 5.6 and -196 degrees C pH 5.7. The change in the quadrupole interaction with pH is, in a simple model, consistent with an ionization of a metal-bound water molecule.", "contents": "Low and high pH form of cadmium carbonic anhydrase determined by nuclear quadrupole interaction. The pH dependence of the nuclear quadrupole interaction between the excited 247-keV state in 111Cd bound to the active site in human carbonic anhydrase B and the nearest protein surroundings has been studied by means of the nuclear spectroscopic technique of perturbed angular correlation of gamma rays. The enzyme has been studied in the pH region 5.6-11.0 at 22 and -196 degrees C. The results show that the Cd enzyme changes from one form at low pH to another form at high pH both at 22 and -196 degrees C. The pK of the transition is 8.9 +/- 0.2 at -196 degrees C and close to 9 at 22 degrees C. Parallel to this transformation, the esterase activity of the Cd enzyme for the hydration of p-nitrophenyl acetate exhibits a pH dependency with a pH of 9.1 +/- 0.2. The sulfonamide inhibitor acetazolamide completely inhibits this activity of the Cd enzyme. The quadrupole interaction parameters for the Cd enzyme are not significantly different at -196 degrees C from those obtained at 22 degrees C. A measurement at 0 degrees C pH 5.7 shows, however, a form different from those at 22 degrees C pH 5.6 and -196 degrees C pH 5.7. The change in the quadrupole interaction with pH is, in a simple model, consistent with an ionization of a metal-bound water molecule."}
{"id": "PMID:2285", "title": "Oxidation-reduction properties of Chromatium vinosum high potential iron-sulfur protein.", "content": "The oxidation-reduction properties of the high potential iron-sulfur protein (HIPIP) from Chromatium vinosum have been investigated. Both equilibrium and kinetic measurements demonstrate electron transport by HIPIP is pH independent in the pH range 7-11. The kinetics of reduction (potassium ferrocyanide, SO2, S2O42-, sodium ascorbate, and Rhodospirillum rubrum cytochrome c2) and oxidation (potassium ferricyanide and Rhodospirillium rubrum cytochrome c2) of HIPIP are reported. Based on the data obtained with different reactants and the influence of ionic strength, pH, and temperature on the kinetics of oxidation and reduction, a number of conclusions can be drawn. (1) HIPIP undergoes rapid outer-sphere electron transfer with no evidence of kinetic complexity and no indication of complex formation with various reactants. (2) The site of oxidation of reduced HIPIP has an apparent negative charge while the site of reduction of oxidized HIPIP is uncharged. (3) HIPIP appears to interact with a physiological reactant (R. rubrum cytochrome c2) at the same site as nonphysiological oxidants or reductants suggesting single minimum energy pathways for the oxidation and reduction processes. (4) Based on a comparison of the rates of oxidation and reduction with different reactants, it appears that steric restrictions and differences in oxidation-reduction potential are less important than electrostatic attraction and/or repulsion in determining the absolute rate constants. (5) The thermodynamic activation parameters indicate that both oxidation and reduction by the iron hexacyanides are driven entropically with the enthalpic terms making no contribution to HIPIP oxidation and a small contribution to HIPIP reduction. Based on the data reported here and available structural and physical-chemical information, possible mechanisms of the oxidation and reduction of HIPIP are discussed and their relative merits analyzed. The more likely mechanisms include electron transfer via a tyrosine residue, electron transfer through a nonaqueous media to the iron-sulfur chromophore, and direct interaction between the iron-sulfur chromophore and the different oxidants and reductants.", "contents": "Oxidation-reduction properties of Chromatium vinosum high potential iron-sulfur protein. The oxidation-reduction properties of the high potential iron-sulfur protein (HIPIP) from Chromatium vinosum have been investigated. Both equilibrium and kinetic measurements demonstrate electron transport by HIPIP is pH independent in the pH range 7-11. The kinetics of reduction (potassium ferrocyanide, SO2, S2O42-, sodium ascorbate, and Rhodospirillum rubrum cytochrome c2) and oxidation (potassium ferricyanide and Rhodospirillium rubrum cytochrome c2) of HIPIP are reported. Based on the data obtained with different reactants and the influence of ionic strength, pH, and temperature on the kinetics of oxidation and reduction, a number of conclusions can be drawn. (1) HIPIP undergoes rapid outer-sphere electron transfer with no evidence of kinetic complexity and no indication of complex formation with various reactants. (2) The site of oxidation of reduced HIPIP has an apparent negative charge while the site of reduction of oxidized HIPIP is uncharged. (3) HIPIP appears to interact with a physiological reactant (R. rubrum cytochrome c2) at the same site as nonphysiological oxidants or reductants suggesting single minimum energy pathways for the oxidation and reduction processes. (4) Based on a comparison of the rates of oxidation and reduction with different reactants, it appears that steric restrictions and differences in oxidation-reduction potential are less important than electrostatic attraction and/or repulsion in determining the absolute rate constants. (5) The thermodynamic activation parameters indicate that both oxidation and reduction by the iron hexacyanides are driven entropically with the enthalpic terms making no contribution to HIPIP oxidation and a small contribution to HIPIP reduction. Based on the data reported here and available structural and physical-chemical information, possible mechanisms of the oxidation and reduction of HIPIP are discussed and their relative merits analyzed. The more likely mechanisms include electron transfer via a tyrosine residue, electron transfer through a nonaqueous media to the iron-sulfur chromophore, and direct interaction between the iron-sulfur chromophore and the different oxidants and reductants."}
{"id": "PMID:2286", "title": "Isolation, chemical, and physical properties of alpha-1-antitrypsin.", "content": "A method of isolation of alpha-1-antitrypsin (alpha-1-AT) in good yield from normal human plasma is described. A key step was affinity chromatography employing an antiserum which had been depleted of alpha-1-AT antibodies. The final preparations were homogeneous by immunological and physicochemical criteria. The specific activity of the purified alpha-1-AT was 0.363 mg of active bovine trypsin inhibited per 1.0 mg of inhibitor. Polyacrylamide gel patterns at both alkaline and acid pH of highly pure preparations frequently, but not invariably, showed multiple hands. Molecular weight studies by sedimentation equilibrium ultracentrifugation in aqueous buffer and in 6 M guanidine as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis suggest that alpha-1-AT is a single polypeptide chain having a molecular weight of 49,500. Other physical and chemical properties of the inhibitor are described. A limited N-terminal sequence (Glu-Asp-Pro-Gln-Gly-Asx-Ala-Ala) was obtained. It was found that alpha-1-AT easily forms polymers and higher aggregates when exposed to denaturing agents such as 8 M urea and 6 M guanidine. The results suggest that aggregation is determined by both covalent and noncovalent forces.", "contents": "Isolation, chemical, and physical properties of alpha-1-antitrypsin. A method of isolation of alpha-1-antitrypsin (alpha-1-AT) in good yield from normal human plasma is described. A key step was affinity chromatography employing an antiserum which had been depleted of alpha-1-AT antibodies. The final preparations were homogeneous by immunological and physicochemical criteria. The specific activity of the purified alpha-1-AT was 0.363 mg of active bovine trypsin inhibited per 1.0 mg of inhibitor. Polyacrylamide gel patterns at both alkaline and acid pH of highly pure preparations frequently, but not invariably, showed multiple hands. Molecular weight studies by sedimentation equilibrium ultracentrifugation in aqueous buffer and in 6 M guanidine as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis suggest that alpha-1-AT is a single polypeptide chain having a molecular weight of 49,500. Other physical and chemical properties of the inhibitor are described. A limited N-terminal sequence (Glu-Asp-Pro-Gln-Gly-Asx-Ala-Ala) was obtained. It was found that alpha-1-AT easily forms polymers and higher aggregates when exposed to denaturing agents such as 8 M urea and 6 M guanidine. The results suggest that aggregation is determined by both covalent and noncovalent forces."}
{"id": "PMID:2287", "title": "Purification and properties of the thermostable acid protease of Penicillium duponti.", "content": "An acid protease produced by the thermophilic fungus Penicillium duponti K 1014 has been purified by consecutive ion-exchange and gel permeation chromatography, and crystallized from aqueous acetone solution. The purified endopeptidase gave a symmetrical schlieren peak by sedimentation velocity, and was found to be homogeneous upon disc gel electrophoresis at pH 9.5. The enzyme was most active at pH 2.5 against milk casein and showed high thermostability. An isoelectric point of 3.81 was found by isoelectric focusing. A minimum molecular weight of 41 590 was calculated from the amino acid composition, adopting an arginine content of one residue per mole of enzyme. This minimum molecular weight is in good agreement with the value of 41 000 previously found by gel permeation (Hashimoto, H., Iwaasa, T., and Yokotsuka, T. (1973), Appl. Microbiol. 25, 578). Besides the thermostability, the purified P. duponti protease differs from other well-characterized acid proteases in that it contains carbohydrate, 4.33% expressed as glucose. The enzyme was not affected by p-bromophenacyl bromide, but was completely inactivated by alpha-diazo-p-bromoacetophenone, diazoacetyl-DL-norleucine methyl ester, and diazoacetylglycine ethyl ester, in the presence of Cu2+. The complete inactivation of the protease by diazoacetyl-DL-norleucine methyl ester resulted in the specific incorporation of 1 mol of norleucine/mol of enzyme. On the basis of similar behavior of other acid proteases toward this inactivator, the results suggest the presence at the active site of an unusually reactive carboxyl group, involved in the catalytic function. The naturally occurring pepsin inhibitor of Streptomyces naniwaensis [Murao, S., and Satoi, S. (1970), Agric. Biol. Chem. 34, 1265] inhibited also the protease, at a threefold molar excess with respect to the enzyme.", "contents": "Purification and properties of the thermostable acid protease of Penicillium duponti. An acid protease produced by the thermophilic fungus Penicillium duponti K 1014 has been purified by consecutive ion-exchange and gel permeation chromatography, and crystallized from aqueous acetone solution. The purified endopeptidase gave a symmetrical schlieren peak by sedimentation velocity, and was found to be homogeneous upon disc gel electrophoresis at pH 9.5. The enzyme was most active at pH 2.5 against milk casein and showed high thermostability. An isoelectric point of 3.81 was found by isoelectric focusing. A minimum molecular weight of 41 590 was calculated from the amino acid composition, adopting an arginine content of one residue per mole of enzyme. This minimum molecular weight is in good agreement with the value of 41 000 previously found by gel permeation (Hashimoto, H., Iwaasa, T., and Yokotsuka, T. (1973), Appl. Microbiol. 25, 578). Besides the thermostability, the purified P. duponti protease differs from other well-characterized acid proteases in that it contains carbohydrate, 4.33% expressed as glucose. The enzyme was not affected by p-bromophenacyl bromide, but was completely inactivated by alpha-diazo-p-bromoacetophenone, diazoacetyl-DL-norleucine methyl ester, and diazoacetylglycine ethyl ester, in the presence of Cu2+. The complete inactivation of the protease by diazoacetyl-DL-norleucine methyl ester resulted in the specific incorporation of 1 mol of norleucine/mol of enzyme. On the basis of similar behavior of other acid proteases toward this inactivator, the results suggest the presence at the active site of an unusually reactive carboxyl group, involved in the catalytic function. The naturally occurring pepsin inhibitor of Streptomyces naniwaensis [Murao, S., and Satoi, S. (1970), Agric. Biol. Chem. 34, 1265] inhibited also the protease, at a threefold molar excess with respect to the enzyme."}
{"id": "PMID:2288", "title": "Biosynthesis of bacterial glycogen. Purification and properties of the Escherichia coli B ADPglucose:1,4-alpha-D-glucan 4-alpha-glucosyltransferase.", "content": "The Escherichia coli B glycogen synthase has been purified to apparent homogeneity with the use of a 4-aminobutyl-Sepharose column. Two fractions of the enzyme were obtained: glycogen synthase I with a specific activity of 380 mumol mg-1 and devoid of branching enzyme activity and glycogen synthase II having a specific activity of 505 mumol mg-1 and containing branching enzyme activity which was 0.1% of the activity observed for the glycogen synthase. Only one protein band was found in disc gel electrophoresis for each glycogen synthase fraction and they were coincident with glycogen synthase activity. One major protein band and one very faint protein band which hardly moved into the gel were observed in sodium dodecyl sulfate gel electrophoresis of the glycogen synthase fractions. The subunit molecular weight of the major protein band in sodium dodecyl sulfate gel electrophoresis of both glycogen synthase fractions was determined to be 49 000 +/- 2 000. The molecular weights of the native enzymes were determined by sucrose density gradient ultracentrifugation. Glycogen synthase I had a molecular weight of 93 000 while glycogen synthase II had a molecular weight of 200 000. On standing at 4 degrees C or at -85 degrees C both enzymes transform into species having molecular weights of 98 000, 135 000, and 185 000. Thus active forms of the E. coli B glycogen synthase can exist as dimers, trimers, and tetramers of the subunit. The enzyme was shown to catalyze transfer of glucose from ADPglucose to maltose and to higher oligosaccharides of the maltodextrin series but not to glucose. 1,5-Gluconolactone was shown to be a potent inhibitor of the glycogen synthase reaction. The glycogen synthase reaction was shown to be reversible. Formation of labeled ADPglucose occurred from either [14C]ADP or [14C]glycogen. The ratio of ADP to ADPglucose at equilibrium at 37 degrees C was determined and was found to vary threefold in the pH range of 5.27-6.82. From these data the ratio of ADP2- to ADPglucose at equilibrium was determined to be 45.8 +/- 4.5. Assuming that deltaF degrees of the hydrolysis of the alpha-1,4-glucosidic linkage is -4.0 kcal the deltaF degrees of hydrolysis of the glucosidic linkage in ADPglucose is -6.3 kcal.", "contents": "Biosynthesis of bacterial glycogen. Purification and properties of the Escherichia coli B ADPglucose:1,4-alpha-D-glucan 4-alpha-glucosyltransferase. The Escherichia coli B glycogen synthase has been purified to apparent homogeneity with the use of a 4-aminobutyl-Sepharose column. Two fractions of the enzyme were obtained: glycogen synthase I with a specific activity of 380 mumol mg-1 and devoid of branching enzyme activity and glycogen synthase II having a specific activity of 505 mumol mg-1 and containing branching enzyme activity which was 0.1% of the activity observed for the glycogen synthase. Only one protein band was found in disc gel electrophoresis for each glycogen synthase fraction and they were coincident with glycogen synthase activity. One major protein band and one very faint protein band which hardly moved into the gel were observed in sodium dodecyl sulfate gel electrophoresis of the glycogen synthase fractions. The subunit molecular weight of the major protein band in sodium dodecyl sulfate gel electrophoresis of both glycogen synthase fractions was determined to be 49 000 +/- 2 000. The molecular weights of the native enzymes were determined by sucrose density gradient ultracentrifugation. Glycogen synthase I had a molecular weight of 93 000 while glycogen synthase II had a molecular weight of 200 000. On standing at 4 degrees C or at -85 degrees C both enzymes transform into species having molecular weights of 98 000, 135 000, and 185 000. Thus active forms of the E. coli B glycogen synthase can exist as dimers, trimers, and tetramers of the subunit. The enzyme was shown to catalyze transfer of glucose from ADPglucose to maltose and to higher oligosaccharides of the maltodextrin series but not to glucose. 1,5-Gluconolactone was shown to be a potent inhibitor of the glycogen synthase reaction. The glycogen synthase reaction was shown to be reversible. Formation of labeled ADPglucose occurred from either [14C]ADP or [14C]glycogen. The ratio of ADP to ADPglucose at equilibrium at 37 degrees C was determined and was found to vary threefold in the pH range of 5.27-6.82. From these data the ratio of ADP2- to ADPglucose at equilibrium was determined to be 45.8 +/- 4.5. Assuming that deltaF degrees of the hydrolysis of the alpha-1,4-glucosidic linkage is -4.0 kcal the deltaF degrees of hydrolysis of the glucosidic linkage in ADPglucose is -6.3 kcal."}
{"id": "PMID:2289", "title": "Bovine procarboxypeptidase A: kinetics of peptide and ester hydrolysis.", "content": "Bovine procarboxypeptidase A exhibits intrinsic hydrolytic activity toward haloacyl amino acids (Behnke and Vallee, 1972), as well as toward conventional peptide and ester substrates for carboxypeptidase A (Bezzone, 1974; Uren and Neurath, 1974). The kinetics of hydrolysis of a series of such substrates by native procarboxypeptidase has now been examined in detail in order to ascertain the extent to which the binding and catalytic sites of carboxypeptidase preexist inthe zymogen. Distinct differences in the substrate binding sites of the zymogen compared with the enzyme are apparent from their respective kinetic profiles as well as from the effects of modifiers on their activities. Substrate activation with the dipeptides BzGly-L-Phe and CbzGly-L-Phe, well known for carboxypeptidase, is exhibited also by the zymogen, but the corresponding substrate inhibition by CbzGly-L-Phe and BzGly-Ophe is absent. Moreover, the substrate inhibition of carboxypeptidase by CbzGlyGly-L-Phe and BzGly-Ophe is replaced by substrate activation in the zymogen...", "contents": "Bovine procarboxypeptidase A: kinetics of peptide and ester hydrolysis. Bovine procarboxypeptidase A exhibits intrinsic hydrolytic activity toward haloacyl amino acids (Behnke and Vallee, 1972), as well as toward conventional peptide and ester substrates for carboxypeptidase A (Bezzone, 1974; Uren and Neurath, 1974). The kinetics of hydrolysis of a series of such substrates by native procarboxypeptidase has now been examined in detail in order to ascertain the extent to which the binding and catalytic sites of carboxypeptidase preexist inthe zymogen. Distinct differences in the substrate binding sites of the zymogen compared with the enzyme are apparent from their respective kinetic profiles as well as from the effects of modifiers on their activities. Substrate activation with the dipeptides BzGly-L-Phe and CbzGly-L-Phe, well known for carboxypeptidase, is exhibited also by the zymogen, but the corresponding substrate inhibition by CbzGly-L-Phe and BzGly-Ophe is absent. Moreover, the substrate inhibition of carboxypeptidase by CbzGlyGly-L-Phe and BzGly-Ophe is replaced by substrate activation in the zymogen..."}
{"id": "PMID:2290", "title": "Ionic influences on the phase transition of dipalmitoylphosphatidylserine.", "content": "The ionization and phase behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphoserine have been investigated under a variety of condtions by several different methods. As measured by turbidity changes, the temperature of the crystal-liquid crystal phase transition of this lipid is influenced by pH  and mono- and divalent cation concentrations. The pH-transition temperature curve is congruent with the curve relating temperature to the degree of ionization of the carboxyl group of the crystalline form. The transition temperature falls from an upper plateau of 72 degrees C at low pH values, where the carboxyl group is fully protonated, to a lower plateau of 55 degrees C at high pH values, where this group is fully ionized. The apparent pK (pH at 50% ionization) of the crystalline form shifts from 6.0 to 4.6 to 3.7 with an increase of NaCl concentration from 10(-3) to 0.1 to l.0 M, respectively. These observations are in accord with a simple theoretical analysis that utilizes diffuse double layer theory and the influence of surface potential on surface concentration of protons. In qualitative terms, an increase in electrolyte concentration reduces the surface potential, the result of which is a diminution of the surface-bulk pH difference and a lowering of the apparent pK. Assuming an area of 50 A2/molecule, the intrinsic pKa (apparent pK corrected for surface pH) of the carboxyl group is 2.7. A 1000-fold change of NaCl concentration produces a very large change in surface potential without influencing the transition temperature of the ionized form of the lipid.", "contents": "Ionic influences on the phase transition of dipalmitoylphosphatidylserine. The ionization and phase behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphoserine have been investigated under a variety of condtions by several different methods. As measured by turbidity changes, the temperature of the crystal-liquid crystal phase transition of this lipid is influenced by pH  and mono- and divalent cation concentrations. The pH-transition temperature curve is congruent with the curve relating temperature to the degree of ionization of the carboxyl group of the crystalline form. The transition temperature falls from an upper plateau of 72 degrees C at low pH values, where the carboxyl group is fully protonated, to a lower plateau of 55 degrees C at high pH values, where this group is fully ionized. The apparent pK (pH at 50% ionization) of the crystalline form shifts from 6.0 to 4.6 to 3.7 with an increase of NaCl concentration from 10(-3) to 0.1 to l.0 M, respectively. These observations are in accord with a simple theoretical analysis that utilizes diffuse double layer theory and the influence of surface potential on surface concentration of protons. In qualitative terms, an increase in electrolyte concentration reduces the surface potential, the result of which is a diminution of the surface-bulk pH difference and a lowering of the apparent pK. Assuming an area of 50 A2/molecule, the intrinsic pKa (apparent pK corrected for surface pH) of the carboxyl group is 2.7. A 1000-fold change of NaCl concentration produces a very large change in surface potential without influencing the transition temperature of the ionized form of the lipid."}
{"id": "PMID:2291", "title": "Light scattering from suspensions of membrane fragments derived from sonication of beef heart mitochondria.", "content": "The intensity of light scattering from suspensions of membrane fragments prepared by sonication of beef heart mitochondria in the presence of EDTA at alkaline pH (ESMP) was determined at 45, 90, and 135 degrees with light of wavelength 546 nm. The dissymmetry ratio Z = I45 degrees c/I135 degrees c, where I45 degrees c and I135 degrees c are the scattering intensities at 45 and 135 degrees extrapolated to zero particle concentration and corrected for reflectance effects, was used to calculate particle size from the Rayleigh-Gans-Debye theory. An average particle diameter D of 184-190 nm was obtained, within the range of particle diameter 50-300 nm determined previously by electron microscopy. This average diameter determined by light scattering is a useful parameter for characterization of ESMP particle size. We propose the term: light scattering average particle diameter, DLS, for this parameter. The refractive index of ESMP was determined to be 1.443 by measurement of scattering intensity in buffer solutions of varying sucrose concentration. The value of Z was independent of sucrose concentration in this determination, showing that the particles are osmotically inactive toward sucrose. The values of average particle diameter DLS and of refractive index fall within the range of validity of the Rayleigh-Gans-Debye theory, for which light scattering changes are attributable solely to dimension change, rather than to change in particle refractive index. Uptake of water accompanying energy-linked salt uptake in ESMP was calculated from light scattering changes to be 0.18 mul of H2O/mg of protein, compared with 0.49 mul of H2O/mg of protein measured by dextran inaccessibility. Measurement of light scattering changes provides a rapid and sensitive method for determining volume changes of ESMP. The magnitude of the volume change observed during energy-linked water and salt uptake and the initial degree of hydration suggests that ESMP are analogous to polyelectrolyte gels with regard to sorption of strong electrolytes and that the Donnan formulation for ion exchange equilibria may be usefully applied to these processes in ESMP.", "contents": "Light scattering from suspensions of membrane fragments derived from sonication of beef heart mitochondria. The intensity of light scattering from suspensions of membrane fragments prepared by sonication of beef heart mitochondria in the presence of EDTA at alkaline pH (ESMP) was determined at 45, 90, and 135 degrees with light of wavelength 546 nm. The dissymmetry ratio Z = I45 degrees c/I135 degrees c, where I45 degrees c and I135 degrees c are the scattering intensities at 45 and 135 degrees extrapolated to zero particle concentration and corrected for reflectance effects, was used to calculate particle size from the Rayleigh-Gans-Debye theory. An average particle diameter D of 184-190 nm was obtained, within the range of particle diameter 50-300 nm determined previously by electron microscopy. This average diameter determined by light scattering is a useful parameter for characterization of ESMP particle size. We propose the term: light scattering average particle diameter, DLS, for this parameter. The refractive index of ESMP was determined to be 1.443 by measurement of scattering intensity in buffer solutions of varying sucrose concentration. The value of Z was independent of sucrose concentration in this determination, showing that the particles are osmotically inactive toward sucrose. The values of average particle diameter DLS and of refractive index fall within the range of validity of the Rayleigh-Gans-Debye theory, for which light scattering changes are attributable solely to dimension change, rather than to change in particle refractive index. Uptake of water accompanying energy-linked salt uptake in ESMP was calculated from light scattering changes to be 0.18 mul of H2O/mg of protein, compared with 0.49 mul of H2O/mg of protein measured by dextran inaccessibility. Measurement of light scattering changes provides a rapid and sensitive method for determining volume changes of ESMP. The magnitude of the volume change observed during energy-linked water and salt uptake and the initial degree of hydration suggests that ESMP are analogous to polyelectrolyte gels with regard to sorption of strong electrolytes and that the Donnan formulation for ion exchange equilibria may be usefully applied to these processes in ESMP."}
{"id": "PMID:2292", "title": "Isolation and characterization of two alkaline ribonucleases from calf serum.", "content": "Treatment of calf serum at 60 degrees C and pH 3.5 followed by chromatography on carboxymethyl (CM) cellulose resulted in the separation of two major peaks of alkaline RNAse activity. One was eluted from CM-cellulose at 0.075 M KCl with an overall purification of 5400-fold and the other was eluted at 0.25 M KCl with a 6700-fold purification. The RNAse eluted from CM-cellulose at 0.075 M KCl was almost completely inhibited by anti-RNAse A serum and by the endogenous RNAse inhibitor and a 33% inhibition was observed in the presence of 5 mM MgCl2. This enzyme seems to be similar or identical to RNAse A. The other RNAse, eluted from CM-cellulose at 0.25 M KCl was not inhibited by anti-RNAse A or 5 mM MgCl2 and was much less sensitive to the endogenous inhibitor. Both enzymes degraded RNA endonucleolytically and the nucleoside monophosphates obtained after partial hydrolysis of RNA by the two serum RNAases were primarily 2'- or 3' -CMP and 2'- or 3' -UMP. Poly(A), native DNA and denatured DNA were degraded slowly or not at all. The RNAase A-like enzyme degraded poly(C) at a significantly faster rate, and poly(U) at a slower rate, than RNA. However, the other serum RNAase was more active with poly(U) than with RNA and almost inactive with poly(C) as the substrate.", "contents": "Isolation and characterization of two alkaline ribonucleases from calf serum. Treatment of calf serum at 60 degrees C and pH 3.5 followed by chromatography on carboxymethyl (CM) cellulose resulted in the separation of two major peaks of alkaline RNAse activity. One was eluted from CM-cellulose at 0.075 M KCl with an overall purification of 5400-fold and the other was eluted at 0.25 M KCl with a 6700-fold purification. The RNAse eluted from CM-cellulose at 0.075 M KCl was almost completely inhibited by anti-RNAse A serum and by the endogenous RNAse inhibitor and a 33% inhibition was observed in the presence of 5 mM MgCl2. This enzyme seems to be similar or identical to RNAse A. The other RNAse, eluted from CM-cellulose at 0.25 M KCl was not inhibited by anti-RNAse A or 5 mM MgCl2 and was much less sensitive to the endogenous inhibitor. Both enzymes degraded RNA endonucleolytically and the nucleoside monophosphates obtained after partial hydrolysis of RNA by the two serum RNAases were primarily 2'- or 3' -CMP and 2'- or 3' -UMP. Poly(A), native DNA and denatured DNA were degraded slowly or not at all. The RNAase A-like enzyme degraded poly(C) at a significantly faster rate, and poly(U) at a slower rate, than RNA. However, the other serum RNAase was more active with poly(U) than with RNA and almost inactive with poly(C) as the substrate."}
{"id": "PMID:2293", "title": "Isolation and characterization of the brush border fraction from newborn rat renal proximal tubule cells.", "content": "A renal brush border fraction was isolated from newborn Sprague-Dawley rats, and its morphological and enzymatic characteristics were studied in comparison to that from the adult. Definite microvillar structures are seen by electron microscopy, and border preparations from the newborn are enriched in known marker enzymes. Though morphological development is more advanced and enzyme specific activities are greater in the adult, polyacrylamide gel electrophoresis of membrane proteins reveals no significant change in pattern with increasing age. These studies suggest that the brush border of the proximal tubule cell is present at birth as a significantly developed structure.", "contents": "Isolation and characterization of the brush border fraction from newborn rat renal proximal tubule cells. A renal brush border fraction was isolated from newborn Sprague-Dawley rats, and its morphological and enzymatic characteristics were studied in comparison to that from the adult. Definite microvillar structures are seen by electron microscopy, and border preparations from the newborn are enriched in known marker enzymes. Though morphological development is more advanced and enzyme specific activities are greater in the adult, polyacrylamide gel electrophoresis of membrane proteins reveals no significant change in pattern with increasing age. These studies suggest that the brush border of the proximal tubule cell is present at birth as a significantly developed structure."}
{"id": "PMID:2294", "title": "Glial fibrillary acidic protein from bovine and rat brain. Degradation in tissues and homogenates.", "content": "Compared with human material glial fibrillary acidic protein isolated from bovine, rat and mouse brain was remarkably homogeneous and migrated as a single band at 54 000 mol. wt. on sodium dodecyl sulfate gel electrophoresis. The protein was extremely susceptible to proteolysis and lower molecular weight components were invariably isolated together with the major species when the brain was not rapidly frozen. Further degradation of the 54 000 mol wt. polypeptide in bovine tissues incubated at 24 degrees C resulted in preparations essentially identical to those previously isolated from human autopsy material and separating into a series of immunologically active polypeptides ranging in molecular weight from 54 000 to approximately 40 500. The gel band pattern obtained after progressively longer periods of autolysis suggested that small fragments were cleaved from the original polypeptide in successive steps of degradation. As in human brain, the lower molecular weight products in the 45 000-40 500 range were more resistant to proteolysis and still present after prolonged periods of tissue autolysis. The effect of the pH and of proteinase inhibitors on degradation was studied in homogenates of bovine brain stem incubated at 37 degrees C. At pH 8.0 PROTEOLYSIS OF The glial fibrillary acidic protein followed essentially the same pattern as in tissue. Cleavage of the major species was not prevented by the addition of proteinase inhibitors. At pH 6.0 and 6.5 a different type of degradation was observed, with rapid breakdown of the protein and loss of immunological activity. Increased solubility in buffer solutions was another effect of autolysis. Compared with cerebral cortex and brain stem, where most of the protein was water soluble, only a small fraction was extracted with buffer from bovine white matter. However, the solubility markedly increased following incubation and comparable amounts were extracted in buffer and in 6 M urea.", "contents": "Glial fibrillary acidic protein from bovine and rat brain. Degradation in tissues and homogenates. Compared with human material glial fibrillary acidic protein isolated from bovine, rat and mouse brain was remarkably homogeneous and migrated as a single band at 54 000 mol. wt. on sodium dodecyl sulfate gel electrophoresis. The protein was extremely susceptible to proteolysis and lower molecular weight components were invariably isolated together with the major species when the brain was not rapidly frozen. Further degradation of the 54 000 mol wt. polypeptide in bovine tissues incubated at 24 degrees C resulted in preparations essentially identical to those previously isolated from human autopsy material and separating into a series of immunologically active polypeptides ranging in molecular weight from 54 000 to approximately 40 500. The gel band pattern obtained after progressively longer periods of autolysis suggested that small fragments were cleaved from the original polypeptide in successive steps of degradation. As in human brain, the lower molecular weight products in the 45 000-40 500 range were more resistant to proteolysis and still present after prolonged periods of tissue autolysis. The effect of the pH and of proteinase inhibitors on degradation was studied in homogenates of bovine brain stem incubated at 37 degrees C. At pH 8.0 PROTEOLYSIS OF The glial fibrillary acidic protein followed essentially the same pattern as in tissue. Cleavage of the major species was not prevented by the addition of proteinase inhibitors. At pH 6.0 and 6.5 a different type of degradation was observed, with rapid breakdown of the protein and loss of immunological activity. Increased solubility in buffer solutions was another effect of autolysis. Compared with cerebral cortex and brain stem, where most of the protein was water soluble, only a small fraction was extracted with buffer from bovine white matter. However, the solubility markedly increased following incubation and comparable amounts were extracted in buffer and in 6 M urea."}
{"id": "PMID:2295", "title": "Studies on the binding of haemoglobin by haptoglobin using electrofocusing and gradient electrophoresis.", "content": "1. Gel electrofocusing followed by gel gradient electrophoresis separated the haptoglobins and their complexes with haemoglobin into characteristic two-dimensional patterns of protein bands. 2. Molecular weights of 107 000, 139 000 and 168 000 were obtained for the three bands seen after a purified preparation of haptoglobin type 1 was partially saturated with haemoglobin. This indicated that free haptoglobin, the intermediate haptoglobin-haemoglobin complex containing one half-haemoglobin and the saturated complex with two half-haemoglobins were present. 3. The three proteins showed considerable microheterogeneity and gave a number of isoelectric points in the pH ranges 4.58-4.77, 5.20-5.40 and 5.74-5.93, free haptoglobin type 1 being the lowest group. These ranges were all 0.15-0.30pH units lower if other values were taken for the isoelectric points of markers used to calibrate the pH gradient. 4. All three proteins were present over a wide range of haemoglobin concentrations, from 0.5% to 92% of that required for saturation. This would be expected if both binding sites have similar affinities for haemoglobin.", "contents": "Studies on the binding of haemoglobin by haptoglobin using electrofocusing and gradient electrophoresis. 1. Gel electrofocusing followed by gel gradient electrophoresis separated the haptoglobins and their complexes with haemoglobin into characteristic two-dimensional patterns of protein bands. 2. Molecular weights of 107 000, 139 000 and 168 000 were obtained for the three bands seen after a purified preparation of haptoglobin type 1 was partially saturated with haemoglobin. This indicated that free haptoglobin, the intermediate haptoglobin-haemoglobin complex containing one half-haemoglobin and the saturated complex with two half-haemoglobins were present. 3. The three proteins showed considerable microheterogeneity and gave a number of isoelectric points in the pH ranges 4.58-4.77, 5.20-5.40 and 5.74-5.93, free haptoglobin type 1 being the lowest group. These ranges were all 0.15-0.30pH units lower if other values were taken for the isoelectric points of markers used to calibrate the pH gradient. 4. All three proteins were present over a wide range of haemoglobin concentrations, from 0.5% to 92% of that required for saturation. This would be expected if both binding sites have similar affinities for haemoglobin."}
{"id": "PMID:2296", "title": "Cytochrome P450cam and its complexes. M\u00f6ssbauer parameters of the heme iron.", "content": "M\u00f6ssbauer spectroscopy has been used to study the heme iron in various states of cytochrome P450cam from the camphor-hydroxylating system of the bacterium Pseudomonas putida. Native, camphor-free P450cam contains low-spin ferric iron, part of which (approx. 50-70%) is converted to the high-spin ferric state upon addition of camphor. The M\u00f6ssbauer spectra of the camphor-free enzyme (S equals 1/2) and of the high-spin component (S equals 5/2) of the camphor complex have been successfully simulated using a model based on crystal-field theory and simple convalency considerations. The native low-spin ferric state of P450cam forms a complex with 2-phenylimidazole, with small changes in the g values and M\u00f6ssbauer spectra. These changes can be accounted for consistently in the crystal-field model referred to above. The addition of putidaredoxin to the camphor-complexed, oxidized P450cam decreases the intensity of the high-spin component and changes its quadrupole splitting. The reduced form of P450cam contrins high-spin ferrous iron, both in the presence and absence of camphor. The complex of reduced P450cam with molecular oxygen is diamagnetic and has a combination of quadrupole splitting and isomer shift that is unusual for a ferrous complex, but strongly resembles that of oxyhemoglobin. These results are compatible with the bound superoxide, Fe3+-O-2, model proposed for oxyhemoglobin (Weiss, J. J. (1964) Nature 202, 83-84). Reduced P450cam and its complexes, oxyP450cam-CO, are all found to be analogous in some respects to the corresponding hemoglobin complexes.", "contents": "Cytochrome P450cam and its complexes. M\u00f6ssbauer parameters of the heme iron. M\u00f6ssbauer spectroscopy has been used to study the heme iron in various states of cytochrome P450cam from the camphor-hydroxylating system of the bacterium Pseudomonas putida. Native, camphor-free P450cam contains low-spin ferric iron, part of which (approx. 50-70%) is converted to the high-spin ferric state upon addition of camphor. The M\u00f6ssbauer spectra of the camphor-free enzyme (S equals 1/2) and of the high-spin component (S equals 5/2) of the camphor complex have been successfully simulated using a model based on crystal-field theory and simple convalency considerations. The native low-spin ferric state of P450cam forms a complex with 2-phenylimidazole, with small changes in the g values and M\u00f6ssbauer spectra. These changes can be accounted for consistently in the crystal-field model referred to above. The addition of putidaredoxin to the camphor-complexed, oxidized P450cam decreases the intensity of the high-spin component and changes its quadrupole splitting. The reduced form of P450cam contrins high-spin ferrous iron, both in the presence and absence of camphor. The complex of reduced P450cam with molecular oxygen is diamagnetic and has a combination of quadrupole splitting and isomer shift that is unusual for a ferrous complex, but strongly resembles that of oxyhemoglobin. These results are compatible with the bound superoxide, Fe3+-O-2, model proposed for oxyhemoglobin (Weiss, J. J. (1964) Nature 202, 83-84). Reduced P450cam and its complexes, oxyP450cam-CO, are all found to be analogous in some respects to the corresponding hemoglobin complexes."}
{"id": "PMID:2297", "title": "Cross partition and determination of net charge of the isoenzymes of enolase.", "content": "Enolase from bakers' yeast was separated into three isoenzymes by countercurrent distribution. The isoenzymes were partitioned in aqueous polymer two-phase systems containing positively charged trimethylamino poly(ethylene glycol) or negatively charged poly(ethylene glycol) sulphonate. The plots of the partition coefficient of each isoenzyme versus pH in the two biphasic systems intersect at pH equal to the isoelectric point. From slopes of the plots, the net charge of the isoenzymes at pH 6.57 was determined to be +2, -3, and -8 respectively.", "contents": "Cross partition and determination of net charge of the isoenzymes of enolase. Enolase from bakers' yeast was separated into three isoenzymes by countercurrent distribution. The isoenzymes were partitioned in aqueous polymer two-phase systems containing positively charged trimethylamino poly(ethylene glycol) or negatively charged poly(ethylene glycol) sulphonate. The plots of the partition coefficient of each isoenzyme versus pH in the two biphasic systems intersect at pH equal to the isoelectric point. From slopes of the plots, the net charge of the isoenzymes at pH 6.57 was determined to be +2, -3, and -8 respectively."}
{"id": "PMID:2298", "title": "Avoidance of strongly chaotropic eluents for immunoaffinity chromatography by chemical modification of immobilized ligand.", "content": "The need for chaotropic eluents in immunoaffinity chromatography is a consequence of the high affinities of antibodies towards their antigens. This affinity is decreased and elution of antiglucagon antibodies from a column of immobilized glucagon can be achieved under mild conditions when the steric complementarity to the antibody binding site is perturbed by selective chemical modification of the hormone. The effects of reaction with 2-hydroxy-5-nitrobenzyl bromide, tetranitromethane and hydrogen peroxide have been studied. Conversely, treatment of immobilized antibodies with 2-hydroxy-5-nitrobenzyl bromide facilitates the elution of glucagon during immunoaffinity chromatography. The general implications of these results are discussed.", "contents": "Avoidance of strongly chaotropic eluents for immunoaffinity chromatography by chemical modification of immobilized ligand. The need for chaotropic eluents in immunoaffinity chromatography is a consequence of the high affinities of antibodies towards their antigens. This affinity is decreased and elution of antiglucagon antibodies from a column of immobilized glucagon can be achieved under mild conditions when the steric complementarity to the antibody binding site is perturbed by selective chemical modification of the hormone. The effects of reaction with 2-hydroxy-5-nitrobenzyl bromide, tetranitromethane and hydrogen peroxide have been studied. Conversely, treatment of immobilized antibodies with 2-hydroxy-5-nitrobenzyl bromide facilitates the elution of glucagon during immunoaffinity chromatography. The general implications of these results are discussed."}
{"id": "PMID:2299", "title": "Release and activation of a particulate bound acid phosphatase from Tetrahymena pyriformis.", "content": "A sedimentable form of acid phosphatase (EC 3.1.3.2) from Tetrahymena pyriformis was found to be solubilized by Triton X-100. The total enzyme activity in the insoluble cell fraction increased almost 200% upon solubilization with Triton X-100 or Nonidet P-40. Removal of membrane lipids and Triton X-100 from the particulate wash solution with a chloroform extraction resulted in non-specific enzyme-protein aggregation which was reversible upon addition of Triton X-100. The results indicate that this acid phosphatase is an integral membrane protein. The pH optima for this particulate bound acid phosphatase was 3.5 with o-carboxyphenyl phosphate and 4.0 with p-nitrophenyl phosphate as substrates. The Km values of each substrate were 3.1 and 0.031 mM, respectively.", "contents": "Release and activation of a particulate bound acid phosphatase from Tetrahymena pyriformis. A sedimentable form of acid phosphatase (EC 3.1.3.2) from Tetrahymena pyriformis was found to be solubilized by Triton X-100. The total enzyme activity in the insoluble cell fraction increased almost 200% upon solubilization with Triton X-100 or Nonidet P-40. Removal of membrane lipids and Triton X-100 from the particulate wash solution with a chloroform extraction resulted in non-specific enzyme-protein aggregation which was reversible upon addition of Triton X-100. The results indicate that this acid phosphatase is an integral membrane protein. The pH optima for this particulate bound acid phosphatase was 3.5 with o-carboxyphenyl phosphate and 4.0 with p-nitrophenyl phosphate as substrates. The Km values of each substrate were 3.1 and 0.031 mM, respectively."}
{"id": "PMID:2300", "title": "Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species.", "content": "The inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the \"Post-Proline Cleaving Enzyme\", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal.", "contents": "Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species. The inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the \"Post-Proline Cleaving Enzyme\", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal."}
{"id": "PMID:2301", "title": "Adenosine phosphyorylase activity as distinct from inosine-guanosine phosphorylase activity in Sarcoma 180 cells and rat liver.", "content": "Adenosine phosphorylase (EC 2.4.2.-) activity present in Sarcoma 180 cells grown in culture and in rat liver, is shown to be distinct from inosine-guanosine phosphorylase by several criteria: (a) treatment of Sarcoma 180 cell extract with p-chloromercuribenzoate inhibited the two activities to a different extent, (b) adenine selectively protected the adenosine phosphorylase activity of Sarcoma 180 and rat liver extract against heat inactivation, while hypoxanthine selectively protected inosine-guanosine phosphorylase activity, (c) at nearly saturating substrate concentrations and using Sarcoma 180 extract, the rates of ribosylation of a mixture of adenine + hypoxanthine or adenine + guanine, but not of hypoxanthine + guanine, were found to be almost equal to the sum of their individual rates as measured separately, (d) inosine selectively inhibited the ribosylation of hypoxanthine and guanine catalysed by Sarcoma 180 and rat liver extract while 2-chloroadenosine selectively inhibited the ribosylation of adenine and N6-furfuryladenine, (e) pH vs. activity curves were similar with hypoxanthine or guanine as the substrate but they were markedly different from the curve with adenine as the substrate. The potential role of adenosine phosphorylase activity in vivo is discussed.", "contents": "Adenosine phosphyorylase activity as distinct from inosine-guanosine phosphorylase activity in Sarcoma 180 cells and rat liver. Adenosine phosphorylase (EC 2.4.2.-) activity present in Sarcoma 180 cells grown in culture and in rat liver, is shown to be distinct from inosine-guanosine phosphorylase by several criteria: (a) treatment of Sarcoma 180 cell extract with p-chloromercuribenzoate inhibited the two activities to a different extent, (b) adenine selectively protected the adenosine phosphorylase activity of Sarcoma 180 and rat liver extract against heat inactivation, while hypoxanthine selectively protected inosine-guanosine phosphorylase activity, (c) at nearly saturating substrate concentrations and using Sarcoma 180 extract, the rates of ribosylation of a mixture of adenine + hypoxanthine or adenine + guanine, but not of hypoxanthine + guanine, were found to be almost equal to the sum of their individual rates as measured separately, (d) inosine selectively inhibited the ribosylation of hypoxanthine and guanine catalysed by Sarcoma 180 and rat liver extract while 2-chloroadenosine selectively inhibited the ribosylation of adenine and N6-furfuryladenine, (e) pH vs. activity curves were similar with hypoxanthine or guanine as the substrate but they were markedly different from the curve with adenine as the substrate. The potential role of adenosine phosphorylase activity in vivo is discussed."}
{"id": "PMID:2302", "title": "Purification and properties of an alpha-amylase inhibitor from wheat.", "content": "Four inhibitors of alpha-amylase (EC 3.2.1.1) were separated from an alcohol extract of wheat by ion-exchange chromatography on DE52-cellulose. One inhibitor, which showed the greatest specificity for human salivary amylase relative to human pancreatic amylase, has been purified by the following steps: (a) alcohol fractionation (60--90%) of water extract (b) ion-exchange chromatography on QAE-Sephadex A-50; (c) re-chromatography on DE52-cellulose and (d) gel filtration on Sephadex G-50. The purified inhibitor is 100 times more specific for human salivary amylase than for human pancreatic amylase. It shows an electrophoretic mobility of 0.2 on disc gel electrophoresis and a molecular weight of about 21 000. This inhibitor contributes about 16% to the total salivary amylase inhibiting power of the wheat extract.", "contents": "Purification and properties of an alpha-amylase inhibitor from wheat. Four inhibitors of alpha-amylase (EC 3.2.1.1) were separated from an alcohol extract of wheat by ion-exchange chromatography on DE52-cellulose. One inhibitor, which showed the greatest specificity for human salivary amylase relative to human pancreatic amylase, has been purified by the following steps: (a) alcohol fractionation (60--90%) of water extract (b) ion-exchange chromatography on QAE-Sephadex A-50; (c) re-chromatography on DE52-cellulose and (d) gel filtration on Sephadex G-50. The purified inhibitor is 100 times more specific for human salivary amylase than for human pancreatic amylase. It shows an electrophoretic mobility of 0.2 on disc gel electrophoresis and a molecular weight of about 21 000. This inhibitor contributes about 16% to the total salivary amylase inhibiting power of the wheat extract."}
{"id": "PMID:2303", "title": "Purification and specificity of prolyl dipeptidase from bovine kidney.", "content": "Prolyl dipeptidase (iminodipeptidase, L-prolyl-amino acid hydrolase, EC 3.4.13.8) was purified 180-fold from bovine kidney. The enzyme which was obtained in a 10% yield was completely separated from a number of known kidney peptidases including an enzyme of very similar substrate specificity, proline aminopeptidase (L-prolyl-peptide hydrolase, EC 3.4.11.5). The specific activity of the enzyme with L-prolylglycine as substrate is 1600 units of activity per mg protein. Optimum activity of the enzyme is at pH 8.75 and the molecular weight on gel filtration was estimated to be 100 000. The isoelectric point of the enzyme is pH 4.25. Studies of substrate specificity showed that the enzyme preferentially hydrolyzes dipeptides and dipeptidyl amides with L-proline or hydroxy-L-proline at the N-terminus. Longer chain substrates with N-terminal proline were not hydrolyzed.", "contents": "Purification and specificity of prolyl dipeptidase from bovine kidney. Prolyl dipeptidase (iminodipeptidase, L-prolyl-amino acid hydrolase, EC 3.4.13.8) was purified 180-fold from bovine kidney. The enzyme which was obtained in a 10% yield was completely separated from a number of known kidney peptidases including an enzyme of very similar substrate specificity, proline aminopeptidase (L-prolyl-peptide hydrolase, EC 3.4.11.5). The specific activity of the enzyme with L-prolylglycine as substrate is 1600 units of activity per mg protein. Optimum activity of the enzyme is at pH 8.75 and the molecular weight on gel filtration was estimated to be 100 000. The isoelectric point of the enzyme is pH 4.25. Studies of substrate specificity showed that the enzyme preferentially hydrolyzes dipeptides and dipeptidyl amides with L-proline or hydroxy-L-proline at the N-terminus. Longer chain substrates with N-terminal proline were not hydrolyzed."}
{"id": "PMID:2304", "title": "Isolation and characterization of beta-glucosidase from the cytosol of rat kidney cortex.", "content": "A procedure is described for the preparation of extensively purified beta-D-glucosidase (EC 3.2.1.21) from the cytosol fraction of rat kidney. The specific activity of the beta-glucosidase in the high speed supernatant (100 000 X g, 90 min) fraction of rat kidney homogenate is 700-fold greater than that in the same fraction from heart, skeletal muscle, lung, spleen, brain or liver. beta-Glucosidase activity co-chromatographs with beta-D-galactosidase, beta-D-fucosidase, alpha-L-arabinosidase and beta-D-xylosidase activities through the last four column steps of the purification and their specific activities are 0.26, 0.39, 0.028 and 0.017 relative to that of beta-glucosidase, respectively. The specific activity of the apparently homogeneous beta-glucosidase is 115 000 nmol of glucose released from 4-methylumbelliferyl-beta-D-glucopyranoside per mg protein per h. All five glycosidase activities possess similar pH dependency (pH optimum, 6--7) and heat lability, and co-migrate on polyacrylamide disc gels at pH 8.9 (RF, 0.67). beta-Glucosidase acitivity is inhibited competitively by glucono-(1 leads to 5)-lactone (KI, 0.61 mM) and non-competitively by a variety of sulfhydryl reagents including N-ethylmaleimide, p-chloromercuribenzoate, 5,5'-dithio-bis(2-nitrobenzoic acid), and iodoacetic acid. Although the enzyme will release glucose from p-nitrophenyl and 4-methylumbelliferyl derivatives of beta-D-glucose, it will not hydrolyze xylosyl-O-serine, beta-D-glucocerebroside, lactose, galactosylovalbumin or trehalose. The enzyme consists of a single polypeptide chain with a molecular weight of 50 000--58 000, has a sedimentation coefficient of 4.41 S and contains a relatively large number of acidic amino acids. A study of the distribution of beta-glucosidase activity in various regions of the dissected rat kidney indicates that the enzyme is probably contained in cells of the proximal convoluted tubule. The enzyme is also present in relatively large amounts in the villus cells, but not crypt cells, of the intestine. The physiological substrate and function of the enzyme are unknown.", "contents": "Isolation and characterization of beta-glucosidase from the cytosol of rat kidney cortex. A procedure is described for the preparation of extensively purified beta-D-glucosidase (EC 3.2.1.21) from the cytosol fraction of rat kidney. The specific activity of the beta-glucosidase in the high speed supernatant (100 000 X g, 90 min) fraction of rat kidney homogenate is 700-fold greater than that in the same fraction from heart, skeletal muscle, lung, spleen, brain or liver. beta-Glucosidase activity co-chromatographs with beta-D-galactosidase, beta-D-fucosidase, alpha-L-arabinosidase and beta-D-xylosidase activities through the last four column steps of the purification and their specific activities are 0.26, 0.39, 0.028 and 0.017 relative to that of beta-glucosidase, respectively. The specific activity of the apparently homogeneous beta-glucosidase is 115 000 nmol of glucose released from 4-methylumbelliferyl-beta-D-glucopyranoside per mg protein per h. All five glycosidase activities possess similar pH dependency (pH optimum, 6--7) and heat lability, and co-migrate on polyacrylamide disc gels at pH 8.9 (RF, 0.67). beta-Glucosidase acitivity is inhibited competitively by glucono-(1 leads to 5)-lactone (KI, 0.61 mM) and non-competitively by a variety of sulfhydryl reagents including N-ethylmaleimide, p-chloromercuribenzoate, 5,5'-dithio-bis(2-nitrobenzoic acid), and iodoacetic acid. Although the enzyme will release glucose from p-nitrophenyl and 4-methylumbelliferyl derivatives of beta-D-glucose, it will not hydrolyze xylosyl-O-serine, beta-D-glucocerebroside, lactose, galactosylovalbumin or trehalose. The enzyme consists of a single polypeptide chain with a molecular weight of 50 000--58 000, has a sedimentation coefficient of 4.41 S and contains a relatively large number of acidic amino acids. A study of the distribution of beta-glucosidase activity in various regions of the dissected rat kidney indicates that the enzyme is probably contained in cells of the proximal convoluted tubule. The enzyme is also present in relatively large amounts in the villus cells, but not crypt cells, of the intestine. The physiological substrate and function of the enzyme are unknown."}
{"id": "PMID:2305", "title": "Studies on (Na+ + K+)-activated ATPase. XXXVIII. A 100 000 molecular weight protein as the low-energy phosphorylated intermediate of the enzyme.", "content": "Phosphorylation of NaI-treated bovine brain cortex microsomes by inorganic phosphate in the presence of Mg2+ and ouabain has been studied at 0 degrees C (pH 7.4) and 20 degrees C (pH 7.0). Nearly maximal (90%) and half-maximal phosphorylation are achieved at 20 degrees C within 2 min with 50--155 and 5.6--17 muM 32Pi, respectively, and at 0 degrees C within 75 s with 300--600 and 33--66 muM 32Pi, respectively. Maximal phosphorylation yields 146 pmol 32P - mg-1 protein. Without ouabain (20 degrees C, pH 7.0) less than 25% of the incorporation observed in the presence of ouabain is reached. Preincubation of the native microsomes with Mg2+ and K+, in order to decompose possibly present high-energy phosphoryl-bonds prior to ouabain treatment, does not affect the maximal phosphate incorporation. This indicates that the inorganic phosphate incorporation is not due to an exchange with high-energy phosphoryl-bonds, which might have been preserved in the microsomal preparations. Phosphorylation of the native microsomes by ATP in the presence of Mg2+ and Na+ reaches 90 and 50% maximal levels within 15--30 s at 0 degrees C and pH 7.4 at concentrations of [gamma-32P]ATP of 5--32 and 0.5--3.5 muM, respectively. The maximal phosphorylation level is 149 pmol 32P-mg-1 protein, equal to that of ouabain-treated microsomes phosphorylated by inorganic phosphate. Both inorganic phosphate and ATP phosphorylate on site per active enzyme subunit of 135 000 molecular weight. From the equilibrium constants for the phosphorylation of ouabain-treated microsomes by inorganic phosphate at 0 degrees C and 20 degrees C standard free-energy changes of --5.4 and --6.8 kcal/mol, respectively, are calculated. These values yield a standard enthalpy change of 14 kcal/mol and an entropy change of 70 cal/mol - degree K. This characterizes the reaction as a process driven by an entropy change. The intermediate formed by phosphorylation with Pi has maximal stability at acidic pH, as is the case for the intermediate formed with ATP. Solubilization in sodium dodecyl sulfate stabilizes the phosphoryl-bond in the pH range of 4--7. The non-solubilized preparation has optimal stability at pH 2--4, the level of which is equal to that of detergent-solubilized intermediate. Sodium dodecyl sulfate gel electrophoresis of the microsomes at pH 3, following incorporation of 32Pi yields 11 protein bands, only one of which (mol. wt 100 000--106 000) carries the radioactive label. This protein has the same molecular weight as the protein, which is phosphorylated by ATP in the presence of Mg2+ and Na+.", "contents": "Studies on (Na+ + K+)-activated ATPase. XXXVIII. A 100 000 molecular weight protein as the low-energy phosphorylated intermediate of the enzyme. Phosphorylation of NaI-treated bovine brain cortex microsomes by inorganic phosphate in the presence of Mg2+ and ouabain has been studied at 0 degrees C (pH 7.4) and 20 degrees C (pH 7.0). Nearly maximal (90%) and half-maximal phosphorylation are achieved at 20 degrees C within 2 min with 50--155 and 5.6--17 muM 32Pi, respectively, and at 0 degrees C within 75 s with 300--600 and 33--66 muM 32Pi, respectively. Maximal phosphorylation yields 146 pmol 32P - mg-1 protein. Without ouabain (20 degrees C, pH 7.0) less than 25% of the incorporation observed in the presence of ouabain is reached. Preincubation of the native microsomes with Mg2+ and K+, in order to decompose possibly present high-energy phosphoryl-bonds prior to ouabain treatment, does not affect the maximal phosphate incorporation. This indicates that the inorganic phosphate incorporation is not due to an exchange with high-energy phosphoryl-bonds, which might have been preserved in the microsomal preparations. Phosphorylation of the native microsomes by ATP in the presence of Mg2+ and Na+ reaches 90 and 50% maximal levels within 15--30 s at 0 degrees C and pH 7.4 at concentrations of [gamma-32P]ATP of 5--32 and 0.5--3.5 muM, respectively. The maximal phosphorylation level is 149 pmol 32P-mg-1 protein, equal to that of ouabain-treated microsomes phosphorylated by inorganic phosphate. Both inorganic phosphate and ATP phosphorylate on site per active enzyme subunit of 135 000 molecular weight. From the equilibrium constants for the phosphorylation of ouabain-treated microsomes by inorganic phosphate at 0 degrees C and 20 degrees C standard free-energy changes of --5.4 and --6.8 kcal/mol, respectively, are calculated. These values yield a standard enthalpy change of 14 kcal/mol and an entropy change of 70 cal/mol - degree K. This characterizes the reaction as a process driven by an entropy change. The intermediate formed by phosphorylation with Pi has maximal stability at acidic pH, as is the case for the intermediate formed with ATP. Solubilization in sodium dodecyl sulfate stabilizes the phosphoryl-bond in the pH range of 4--7. The non-solubilized preparation has optimal stability at pH 2--4, the level of which is equal to that of detergent-solubilized intermediate. Sodium dodecyl sulfate gel electrophoresis of the microsomes at pH 3, following incorporation of 32Pi yields 11 protein bands, only one of which (mol. wt 100 000--106 000) carries the radioactive label. This protein has the same molecular weight as the protein, which is phosphorylated by ATP in the presence of Mg2+ and Na+."}
{"id": "PMID:2306", "title": "Partial purification and properties of a chromatin-associated phosphoprotein kinase from rat liver nuclei.", "content": "A phosphoprotein kinase (EC 2.7.1.37) KIVb, from rat liver nuclei, was purified 75-fold by phosphocellulose chromatography and gel filtration on Sephadex G-200. The enzyme, which has an apparent molecular weight of 55 000, phosphorylates casein and chromatin-bound nonhistone proteins more readily than histones or ribosomal proteins. It exhibits an absolute requirement for divalent cation with optimum activity at 15--20 mM Mg2+. Maximal kinase activity is achieved at 100 mM NaCl. The pH vs. activity curve is biphasic with optima at pH 6.5 and pH 8.0. The Km value for casein is 280 mug/ml and the Km for ATP is 6-10(-6) M. Kinase KIVb phosphorylates numerous nonhistone nuclear proteins as shown by electrophoretic analysis. The addition of kinase KIVb to reaction mixtures containing nonhistone proteins results in the phosphorylation of a spectrum of polypeptides similar to those that are phosphorylated by endogenous nuclear kinases. Nonhistone proteins bound to chromatin appear to be better substrates for KIVb than nonhistones dissociated from chromatin. A comparison of nuclear phosphoproteins phosphorylated either in the intact animal or in vitro (by the addition of kinase KIVb) indicates some differences and some similarities in the patterns of phosphorylation.", "contents": "Partial purification and properties of a chromatin-associated phosphoprotein kinase from rat liver nuclei. A phosphoprotein kinase (EC 2.7.1.37) KIVb, from rat liver nuclei, was purified 75-fold by phosphocellulose chromatography and gel filtration on Sephadex G-200. The enzyme, which has an apparent molecular weight of 55 000, phosphorylates casein and chromatin-bound nonhistone proteins more readily than histones or ribosomal proteins. It exhibits an absolute requirement for divalent cation with optimum activity at 15--20 mM Mg2+. Maximal kinase activity is achieved at 100 mM NaCl. The pH vs. activity curve is biphasic with optima at pH 6.5 and pH 8.0. The Km value for casein is 280 mug/ml and the Km for ATP is 6-10(-6) M. Kinase KIVb phosphorylates numerous nonhistone nuclear proteins as shown by electrophoretic analysis. The addition of kinase KIVb to reaction mixtures containing nonhistone proteins results in the phosphorylation of a spectrum of polypeptides similar to those that are phosphorylated by endogenous nuclear kinases. Nonhistone proteins bound to chromatin appear to be better substrates for KIVb than nonhistones dissociated from chromatin. A comparison of nuclear phosphoproteins phosphorylated either in the intact animal or in vitro (by the addition of kinase KIVb) indicates some differences and some similarities in the patterns of phosphorylation."}
{"id": "PMID:2307", "title": "Purification and some properties of rat liver cysteine oxidase (cysteine dioxygenase).", "content": "Cysteine oxidase (cysteine dioxygenase, EC 1.13.11.20) was purified approximately 1000-fold from rat liver. The purified enzyme (protein-B) was obtained as an inactive form, which was activated by anaerobic preincubation with L-cysteine. The active form of protein-B was inactivated during aerobic incubation to produce cysteine sulfinate. This inactivation of protein-B was protected by a distinct protein in rat liver cytoplasm, namely stabilizing protein (protein-A). The Ka and Km values for L-cysteine were 0.8-10(-3) M and 1.3-10(-3) M respectively. The enzyme was strongly inhibited by Cu+ and/or Fe2+ chelating agents but not by Cu2+ chelating agent. The optimum pH of enzyme reaction was 8.5-9.5 while that of enzyme activation was 6.8-9.5, with a broad peak.", "contents": "Purification and some properties of rat liver cysteine oxidase (cysteine dioxygenase). Cysteine oxidase (cysteine dioxygenase, EC 1.13.11.20) was purified approximately 1000-fold from rat liver. The purified enzyme (protein-B) was obtained as an inactive form, which was activated by anaerobic preincubation with L-cysteine. The active form of protein-B was inactivated during aerobic incubation to produce cysteine sulfinate. This inactivation of protein-B was protected by a distinct protein in rat liver cytoplasm, namely stabilizing protein (protein-A). The Ka and Km values for L-cysteine were 0.8-10(-3) M and 1.3-10(-3) M respectively. The enzyme was strongly inhibited by Cu+ and/or Fe2+ chelating agents but not by Cu2+ chelating agent. The optimum pH of enzyme reaction was 8.5-9.5 while that of enzyme activation was 6.8-9.5, with a broad peak."}
{"id": "PMID:2308", "title": "Conformations of lysine-sensitive aspartokinase.", "content": "1. The technique of differential thermal and proteolytic inactivation has been employed as a conformational probe for the lysine-sensitive aspartokinase (EC 2.7.2.4) of Escherichia coli B. 2. L-Amino acid inhibitors of this enzyme each induce a characteristic enzyme conformation. This is evidenced by rates of thermal and proteolytic inactivation and Arrhenius activation energies for thermal inactivation which are characteristic of the amino acid present. 3. Phenylalanine and leucine binding are mutually exclusive as evidenced by competitive behavior in thermal inactivation experiments, suggesting a hydrophobic amino acid binding site with broad specificity. 4. The phenylalanine-dependent conformation and the leucine-dependent conformation differ considerably. In comparison with the native enzyme, the former is more labile to proteolysis by trypsin whereas the latter is more stable. First-order rate constants for thermal inactivation of the phenylalanine- and leucine-dependent conformations are, respectively, about one-half and one-tenth that of the native enzyme. 5. Items 3 and 4 taken together suggest that the conformations are ligand induced and do not arise via ligand stabilization of spontaneously arising conformers.", "contents": "Conformations of lysine-sensitive aspartokinase. 1. The technique of differential thermal and proteolytic inactivation has been employed as a conformational probe for the lysine-sensitive aspartokinase (EC 2.7.2.4) of Escherichia coli B. 2. L-Amino acid inhibitors of this enzyme each induce a characteristic enzyme conformation. This is evidenced by rates of thermal and proteolytic inactivation and Arrhenius activation energies for thermal inactivation which are characteristic of the amino acid present. 3. Phenylalanine and leucine binding are mutually exclusive as evidenced by competitive behavior in thermal inactivation experiments, suggesting a hydrophobic amino acid binding site with broad specificity. 4. The phenylalanine-dependent conformation and the leucine-dependent conformation differ considerably. In comparison with the native enzyme, the former is more labile to proteolysis by trypsin whereas the latter is more stable. First-order rate constants for thermal inactivation of the phenylalanine- and leucine-dependent conformations are, respectively, about one-half and one-tenth that of the native enzyme. 5. Items 3 and 4 taken together suggest that the conformations are ligand induced and do not arise via ligand stabilization of spontaneously arising conformers."}
{"id": "PMID:2309", "title": "The sulphatase of ox liver. XIX. On the nature of the polymeric forms of sulphatase A present in dilute solutions.", "content": "Weight-average elution volumes of sulphatase A (an arylsulphate sulphohydrolase, EC 3.1.6.1) from Sephadex G-200 have been determined as functions of protein concentration, pH, ionic strength and temperature. The results are used to calculate the apparent association equilibrium constants for tetramer formation and the associated standard-state thermodynamic parameters. While the apparent association constant decreased from 10(28) to 10(21) M-3 on increasing the pH from 4.5 to 5.6 at ionic strength 0.1, at any particular pH value studied it was relatively insensitive to temperature variation so that deltaH is close to zero and tetramer formation in solution is associated with a positive entropy change. At pH 5.0, increasing the ionic strength from 0.1 to 2 decreased the association constant by a factor of 100. Methylumbelliferone sulphate has no effect on the association of sulphatase A. The equilibrium results are used to define the degree of association of sulphatase A likely to encountered in experiments designed to elucidate its kinetic properties. In the liver lysosome, the tetramer is probably the dominant species. The monomer and tetramer of sulphatase A have similar, or identical, specific activities with nitrocatechol sulphate and 4-methylumbelliferone sulphate as substrates. With nitrocatechol sulphate, sulphatase A shows Michaelis kinetics under conditions where the monomer is the dominant species and non-Michaelis kinetics where the tetramer is dominant. There is apparently a negative cooperativity between the monomer units in the tetramer. In 2 mM sodium taurodeoxycholate and 0.035 M MnCl2, but not in 0.1 M NaCl, the tetramer shows Michaelis kinetics. This is not due to dissociation of the tetramer. The critical micellar concentration of sodium taurodeoxycholate is about 0.8 mM in both 0.1 M NaCl and 0.035 M McCl2 but the aggregation number is greater in the latter.", "contents": "The sulphatase of ox liver. XIX. On the nature of the polymeric forms of sulphatase A present in dilute solutions. Weight-average elution volumes of sulphatase A (an arylsulphate sulphohydrolase, EC 3.1.6.1) from Sephadex G-200 have been determined as functions of protein concentration, pH, ionic strength and temperature. The results are used to calculate the apparent association equilibrium constants for tetramer formation and the associated standard-state thermodynamic parameters. While the apparent association constant decreased from 10(28) to 10(21) M-3 on increasing the pH from 4.5 to 5.6 at ionic strength 0.1, at any particular pH value studied it was relatively insensitive to temperature variation so that deltaH is close to zero and tetramer formation in solution is associated with a positive entropy change. At pH 5.0, increasing the ionic strength from 0.1 to 2 decreased the association constant by a factor of 100. Methylumbelliferone sulphate has no effect on the association of sulphatase A. The equilibrium results are used to define the degree of association of sulphatase A likely to encountered in experiments designed to elucidate its kinetic properties. In the liver lysosome, the tetramer is probably the dominant species. The monomer and tetramer of sulphatase A have similar, or identical, specific activities with nitrocatechol sulphate and 4-methylumbelliferone sulphate as substrates. With nitrocatechol sulphate, sulphatase A shows Michaelis kinetics under conditions where the monomer is the dominant species and non-Michaelis kinetics where the tetramer is dominant. There is apparently a negative cooperativity between the monomer units in the tetramer. In 2 mM sodium taurodeoxycholate and 0.035 M MnCl2, but not in 0.1 M NaCl, the tetramer shows Michaelis kinetics. This is not due to dissociation of the tetramer. The critical micellar concentration of sodium taurodeoxycholate is about 0.8 mM in both 0.1 M NaCl and 0.035 M McCl2 but the aggregation number is greater in the latter."}
{"id": "PMID:2310", "title": "Purification and characterization of an extracellular exo-D-galacturonanase of Aspergillus niger.", "content": "A D-galacturonanase (EC 3.2.1.67) catalyzing the degradation of D-galacturonans by terminal action pattern was purified from a culture filtrate of Aspergillus niger by a procedure including the salting-out with ammonium sulfate, precipitation by ethanol, chromatography on DEAE-cellulose, and gel chromatography on Sephadex G-100. The obtained preparation was slightly contaminated by an enzymically inactive protein fraction. Maximum activity and stability of the enzyme was observed at pH 5.2. The enzyme degrades digalacturonic acid, p-nitrophenyl-alpha-D-galactopyranuronide, as well as oligogalacturonides containing at the nonreducing end 4-deoxy-L-threo-hexa-4-enopyranosyluronate. It differs from all A. niger enzymes so far described which degrade D-galaturonans by the terminal action pattern, in not clearly preferring low-molecular substrates. It is therefore classified as an exo-D-galacturonanase.", "contents": "Purification and characterization of an extracellular exo-D-galacturonanase of Aspergillus niger. A D-galacturonanase (EC 3.2.1.67) catalyzing the degradation of D-galacturonans by terminal action pattern was purified from a culture filtrate of Aspergillus niger by a procedure including the salting-out with ammonium sulfate, precipitation by ethanol, chromatography on DEAE-cellulose, and gel chromatography on Sephadex G-100. The obtained preparation was slightly contaminated by an enzymically inactive protein fraction. Maximum activity and stability of the enzyme was observed at pH 5.2. The enzyme degrades digalacturonic acid, p-nitrophenyl-alpha-D-galactopyranuronide, as well as oligogalacturonides containing at the nonreducing end 4-deoxy-L-threo-hexa-4-enopyranosyluronate. It differs from all A. niger enzymes so far described which degrade D-galaturonans by the terminal action pattern, in not clearly preferring low-molecular substrates. It is therefore classified as an exo-D-galacturonanase."}
{"id": "PMID:2311", "title": "The biosynthesis of multi-L-arginyl-poly(L-aspartic acid) in the filamentous cyanobacterium Anabaena cylindrica.", "content": "The cyanobacteria produce multi-L-arginyl-poly (aspartic acid), a high molecular weight (Mr=25 000-125 000) branched polypeptide consisting of a poly(aspartic acid) core with L-arginyl residues peptide bonded to each free carboxyl group of the poly(aspartic acid). An enzyme which will elongate Arg-poly(Asp) has been isolated and purified 92-fold from the filamentous cyanobacterium Anabaena cylindrica. The enzyme incorporates arginine and aspartic acid into Arg-poly(Asp) in a reaction which requires ATP, KCl, MgCl2, and a sulfhydryl reagent. The enzymatic incorporation of arginine is dependent upon the presence of L-aspartic acid but not visa versa, a finding which suggests the order of amino acid addition to the branched polypeptide-aspartic acid is added to the core followed by the attachment of an arginine branch. The elongation of Arg-poly(Asp) in-vitro is insensitive to the addition of protein synthesis inhibitors and to the addition of nucleases. These findings support the notion previosly suggested from in-vivo studies that Arg-poly(Asp) is synthesized via a non-ribosomal route and also demonstrate that amino-acetylated transfer-RNAs play no part in at least one step of the biosynthetic mechanism.", "contents": "The biosynthesis of multi-L-arginyl-poly(L-aspartic acid) in the filamentous cyanobacterium Anabaena cylindrica. The cyanobacteria produce multi-L-arginyl-poly (aspartic acid), a high molecular weight (Mr=25 000-125 000) branched polypeptide consisting of a poly(aspartic acid) core with L-arginyl residues peptide bonded to each free carboxyl group of the poly(aspartic acid). An enzyme which will elongate Arg-poly(Asp) has been isolated and purified 92-fold from the filamentous cyanobacterium Anabaena cylindrica. The enzyme incorporates arginine and aspartic acid into Arg-poly(Asp) in a reaction which requires ATP, KCl, MgCl2, and a sulfhydryl reagent. The enzymatic incorporation of arginine is dependent upon the presence of L-aspartic acid but not visa versa, a finding which suggests the order of amino acid addition to the branched polypeptide-aspartic acid is added to the core followed by the attachment of an arginine branch. The elongation of Arg-poly(Asp) in-vitro is insensitive to the addition of protein synthesis inhibitors and to the addition of nucleases. These findings support the notion previosly suggested from in-vivo studies that Arg-poly(Asp) is synthesized via a non-ribosomal route and also demonstrate that amino-acetylated transfer-RNAs play no part in at least one step of the biosynthetic mechanism."}
{"id": "PMID:2312", "title": "Separation of subchloroplast membrane particles by counter-current distribution.", "content": "Counter-current distribution in an aqueous Dextran-polyethylene glycol two-phase system has been used to fractionate membrane fragments obtained by press treatment of Class II chloroplasts. By the counter-current distribution technique membrane particles are separated according to their surface properties such as charge and hydrophobicity. The fractions obtained were analysed with respect to photochemical activities, chlorophyll and P-700 contents. The Photosystem II enrichment after counter-current distribution was better than that obtained by differential centrifugation of the disrupted chloroplasts. However, the best separation of Photosystem I and II enriched particles could be achieved if differential centrifugation was combined with the counter-current distribution technique. Each centrifugal fraction could be further separated into Photosystems I and II enriched fractions since the Photosystem II particles preferred the dextran-rich bottom phase while the Photosystem I particles preferred the polyethylene glycol-rich top phase. By this procedure it was possible, without the use of detergents, to obtain vesicles which were more enriched in Photosystem II as compared to intact grana stacks. The partition behaviour of undisrupted Class II chloroplasts and the Photosystem I centrifugal fraction was the same. This similarity indicated that the membrane which is exposed to the surrounding polymers by the Class II chloroplasts is the Photosystem I rich membrane of the stroma lamellae.", "contents": "Separation of subchloroplast membrane particles by counter-current distribution. Counter-current distribution in an aqueous Dextran-polyethylene glycol two-phase system has been used to fractionate membrane fragments obtained by press treatment of Class II chloroplasts. By the counter-current distribution technique membrane particles are separated according to their surface properties such as charge and hydrophobicity. The fractions obtained were analysed with respect to photochemical activities, chlorophyll and P-700 contents. The Photosystem II enrichment after counter-current distribution was better than that obtained by differential centrifugation of the disrupted chloroplasts. However, the best separation of Photosystem I and II enriched particles could be achieved if differential centrifugation was combined with the counter-current distribution technique. Each centrifugal fraction could be further separated into Photosystems I and II enriched fractions since the Photosystem II particles preferred the dextran-rich bottom phase while the Photosystem I particles preferred the polyethylene glycol-rich top phase. By this procedure it was possible, without the use of detergents, to obtain vesicles which were more enriched in Photosystem II as compared to intact grana stacks. The partition behaviour of undisrupted Class II chloroplasts and the Photosystem I centrifugal fraction was the same. This similarity indicated that the membrane which is exposed to the surrounding polymers by the Class II chloroplasts is the Photosystem I rich membrane of the stroma lamellae."}
{"id": "PMID:2313", "title": "Stimulation of ATP synthesis in Halobacterium halobium R1 by light-induced or artifically created proton electrochemical potential gradients across the cell membrane.", "content": "The relationship between proton movement and phosphorylation in Halo-bacterium halobium R1 has been investigated under anaerobic conditions. The light-induced changes in the bacteriorhodopsin are accompanied by proton movements across the membrane which result in pH changes in the suspending medium. The initial alkaline shift is shown to be closely paralleled by (and hence correlated with) ATP synthesis. Acidification of the medium in the presence of valinomycin, under conditions of low external potassium, brings about ATP synthesis in the dark.", "contents": "Stimulation of ATP synthesis in Halobacterium halobium R1 by light-induced or artifically created proton electrochemical potential gradients across the cell membrane. The relationship between proton movement and phosphorylation in Halo-bacterium halobium R1 has been investigated under anaerobic conditions. The light-induced changes in the bacteriorhodopsin are accompanied by proton movements across the membrane which result in pH changes in the suspending medium. The initial alkaline shift is shown to be closely paralleled by (and hence correlated with) ATP synthesis. Acidification of the medium in the presence of valinomycin, under conditions of low external potassium, brings about ATP synthesis in the dark."}
{"id": "PMID:2314", "title": "Mechanism of active shrinkage in mitochondria. II. Coupling between strong electrolyte fluxes.", "content": "1. Addition of succinate to valinomycin-treated mitochondria incubated in KCL causes a large electrolyte penetration. The process depends on a steady supply of energy and involves a continuous net extrusion of protons. Rates of respiration and of electrolyte penetration proceed in a parallel manner. 2. A passive penetration of K+ salt of permeant anions occurs in respiratory-inhibited mitochondria after addition of valinomycin. Addition of succinate at the end of the passive swelling starts an active extrusion of anions and cations with restoration of the initial volume. The shrinkage is accompanied by a slow reuptake of protons. The initiation of the active shrinkage correlates with the degree of stretching of the inner membrane. The extrusion of electrolytes is inhibited by nigericin, while it is only slightly sensitive to variations of the valinomycin concentration larger than two orders of magnitude. 3. Passive swelling and active shrinkage occurs also when K+ is replaced by a large variety of organic cations. The rate of organic cation penetration is enhanced by tetraphenylboron, while the rate of electrolyte extrusion is insensitive to variation of the tetraphenylboron concentration. 4. Active shrinkage, either with K+ or organic cation salts, is inhibited by weak acids. The phosphate inhibition is removed by SH inhibitors. The active shrinkage is also inhibited by mersalyl to an extent of about 60%. 5. Three models of active shrinkage are discussed: (a) mechanoprotein, (b) electrogenic proton pump, and (c) proton-driven cation anion pump.", "contents": "Mechanism of active shrinkage in mitochondria. II. Coupling between strong electrolyte fluxes. 1. Addition of succinate to valinomycin-treated mitochondria incubated in KCL causes a large electrolyte penetration. The process depends on a steady supply of energy and involves a continuous net extrusion of protons. Rates of respiration and of electrolyte penetration proceed in a parallel manner. 2. A passive penetration of K+ salt of permeant anions occurs in respiratory-inhibited mitochondria after addition of valinomycin. Addition of succinate at the end of the passive swelling starts an active extrusion of anions and cations with restoration of the initial volume. The shrinkage is accompanied by a slow reuptake of protons. The initiation of the active shrinkage correlates with the degree of stretching of the inner membrane. The extrusion of electrolytes is inhibited by nigericin, while it is only slightly sensitive to variations of the valinomycin concentration larger than two orders of magnitude. 3. Passive swelling and active shrinkage occurs also when K+ is replaced by a large variety of organic cations. The rate of organic cation penetration is enhanced by tetraphenylboron, while the rate of electrolyte extrusion is insensitive to variation of the tetraphenylboron concentration. 4. Active shrinkage, either with K+ or organic cation salts, is inhibited by weak acids. The phosphate inhibition is removed by SH inhibitors. The active shrinkage is also inhibited by mersalyl to an extent of about 60%. 5. Three models of active shrinkage are discussed: (a) mechanoprotein, (b) electrogenic proton pump, and (c) proton-driven cation anion pump."}
{"id": "PMID:2315", "title": "Inhibitory effect of p-nitrothiophenol in the light on the photosystem II activity of spinach chloroplasts.", "content": "The treatment of spinach chloroplasts with p-nitrothiophenol in the light at acidic and neutral pH'S caused specific inhibition of the Photosystem II activity, whereas the same treatment in the dark did not affect the activity at all. The photosystem I activity was not inhibited by p-nitrothiophenol both in the light and in the dark. The inhibition was accompanied by changes of fluorescence from chloroplasts. As observed at room temperature, the 685-nm band was lowered by the p-nitrothiophenol treatment in the light and, at liquid nitrogen temperature, the relative height of the 695-nm band to the 685-nm band increased and the 695-nm band shifted to longer wavelengths. The action spectra for these effects of p-nitrothiophenol on the activity and fluorescence showed a peak at 670 nm with a red drop at longer wavelengths. It was concluded that the light absorbed by Photosystem II is responsible for the chemical modification of chloroplasts with p-nitrothiopehnol to causing the specific inhibition of Photosystem II.", "contents": "Inhibitory effect of p-nitrothiophenol in the light on the photosystem II activity of spinach chloroplasts. The treatment of spinach chloroplasts with p-nitrothiophenol in the light at acidic and neutral pH'S caused specific inhibition of the Photosystem II activity, whereas the same treatment in the dark did not affect the activity at all. The photosystem I activity was not inhibited by p-nitrothiophenol both in the light and in the dark. The inhibition was accompanied by changes of fluorescence from chloroplasts. As observed at room temperature, the 685-nm band was lowered by the p-nitrothiophenol treatment in the light and, at liquid nitrogen temperature, the relative height of the 695-nm band to the 685-nm band increased and the 695-nm band shifted to longer wavelengths. The action spectra for these effects of p-nitrothiophenol on the activity and fluorescence showed a peak at 670 nm with a red drop at longer wavelengths. It was concluded that the light absorbed by Photosystem II is responsible for the chemical modification of chloroplasts with p-nitrothiopehnol to causing the specific inhibition of Photosystem II."}
{"id": "PMID:2316", "title": "Relations between the electrical potential, pH gradient, proton flux and phosphorylation in the photosynthetic membrane.", "content": "The transmembrane electrical potential (deltaphi), the proton flux (H+), the rate of electron transport (e), the pH gradient (deltapH) and the rate of phosphorylation (ATP) were measured in chloroplasts of spinach. Photosynthesis was excited periodically with flashes of variable frequencies and intensities. A new method is described for determining the rate of electron transport and proton flux. Under conditions where the rate of electron transport and proton flux are not pH controlled the following correlations were found in the range 50 mV less than or equal to deltaphi less than or equal to 125 mV and 1.8 less than or equal to deltapH less than or equal to 2.7: (1) The pH gradient, deltapH, increases with H+ independently of Phout between 7-9. (2) The rate of phosphorylation, ATP, depends exponentially on deltapH (at constant deltaphi) and is independent of pHout between 7-9. (3) The rate of phosphorylation, ATP, depends also on deltaphi (at constant deltapH and at constant proton flux H+). (4) The proton flux via the ATPase pathway, Hp+, depends non-linearly on the ratio of the proton concentrations: Hp+ approximately (Hin+/Hout+)b, (b=2.3--2.6). The proton flux via the basal pathway, Hb+, depends linearly on the ratio of the proton concentrations: Hb+ approximately (Hin/Hout). (5) The ratio deltaH+/ATP (e/ATP, i.e. the ratio of the total proton flux, Hp+ + Hb+, and the rate of ATP formation, ATP, depends strongly on deltaphi and on deltapH. The ratio is deltaH+/ATP approximately 3 (e/ATP approximately 1.5) at deltapH 2.7 and deltaphi = 125 mV. (6) It is supposed that the reason for the dependence of deltaH+/ATP on deltaphi anddeltapH is the different functional dependence of the basal proton flux Hb+ and the phosphorylating proton flux Hp+ on deltapH and deltaphi. The calculation of deltaH+/ATP on the basis of this assumption is in fair agreement with the experimental values. Also the \"threshold\" effects can be explained in this way. (7) The ratio of deltaHp+/ATP, i.e. the ratio of the phosphorylating proton flux Hp+ and ATP, is deltaHp+/ATP APPROXIMATELY 2.4.", "contents": "Relations between the electrical potential, pH gradient, proton flux and phosphorylation in the photosynthetic membrane. The transmembrane electrical potential (deltaphi), the proton flux (H+), the rate of electron transport (e), the pH gradient (deltapH) and the rate of phosphorylation (ATP) were measured in chloroplasts of spinach. Photosynthesis was excited periodically with flashes of variable frequencies and intensities. A new method is described for determining the rate of electron transport and proton flux. Under conditions where the rate of electron transport and proton flux are not pH controlled the following correlations were found in the range 50 mV less than or equal to deltaphi less than or equal to 125 mV and 1.8 less than or equal to deltapH less than or equal to 2.7: (1) The pH gradient, deltapH, increases with H+ independently of Phout between 7-9. (2) The rate of phosphorylation, ATP, depends exponentially on deltapH (at constant deltaphi) and is independent of pHout between 7-9. (3) The rate of phosphorylation, ATP, depends also on deltaphi (at constant deltapH and at constant proton flux H+). (4) The proton flux via the ATPase pathway, Hp+, depends non-linearly on the ratio of the proton concentrations: Hp+ approximately (Hin+/Hout+)b, (b=2.3--2.6). The proton flux via the basal pathway, Hb+, depends linearly on the ratio of the proton concentrations: Hb+ approximately (Hin/Hout). (5) The ratio deltaH+/ATP (e/ATP, i.e. the ratio of the total proton flux, Hp+ + Hb+, and the rate of ATP formation, ATP, depends strongly on deltaphi and on deltapH. The ratio is deltaH+/ATP approximately 3 (e/ATP approximately 1.5) at deltapH 2.7 and deltaphi = 125 mV. (6) It is supposed that the reason for the dependence of deltaH+/ATP on deltaphi anddeltapH is the different functional dependence of the basal proton flux Hb+ and the phosphorylating proton flux Hp+ on deltapH and deltaphi. The calculation of deltaH+/ATP on the basis of this assumption is in fair agreement with the experimental values. Also the \"threshold\" effects can be explained in this way. (7) The ratio of deltaHp+/ATP, i.e. the ratio of the phosphorylating proton flux Hp+ and ATP, is deltaHp+/ATP APPROXIMATELY 2.4."}
{"id": "PMID:2317", "title": "A possible mechanism of the generation of singlet molecular oxygen in nadph-dependent microsomal lipid peroxidation.", "content": "A simplified system, consisting of NADPH, Fe3+-ADP, EDTA, liposomes, NADPH-cytochrome c reductase and Tris - HCl buffer (pH 6.8), has been employed in studies of the generation of singlet oxygen in NADPH-dependent microsomal lipid peroxidation. The light emitted by the system involves 1deltag type molecular oxygen identifiable by its characteristic emission spectrum and its behavior with beta-carotene. The generation of another excited species (a compound in the triplet state) could be demonstrated in this system by changes of light intensity and emission spectra which arise from photosensitizer (9,10-dibromoanthracene sulfonate, eosin, Rose-Bengal)-mediated energy transfers. Chemiluminescence in the visible region was markedly quenched by various radical trappers and by an inhibitor of NADPH-cytochrome c reductase, but not by superoxide dismutase. During the early stage of lipid peroxidation, the intensity of chemiluminescence was proportional to the square of the concentration of lipid peroxide. These characteristics suggest that singlet oxygen and a compound in the triplet state (probably a carbonyl compound) are generated by a self-reaction of lipid peroxy radicals.", "contents": "A possible mechanism of the generation of singlet molecular oxygen in nadph-dependent microsomal lipid peroxidation. A simplified system, consisting of NADPH, Fe3+-ADP, EDTA, liposomes, NADPH-cytochrome c reductase and Tris - HCl buffer (pH 6.8), has been employed in studies of the generation of singlet oxygen in NADPH-dependent microsomal lipid peroxidation. The light emitted by the system involves 1deltag type molecular oxygen identifiable by its characteristic emission spectrum and its behavior with beta-carotene. The generation of another excited species (a compound in the triplet state) could be demonstrated in this system by changes of light intensity and emission spectra which arise from photosensitizer (9,10-dibromoanthracene sulfonate, eosin, Rose-Bengal)-mediated energy transfers. Chemiluminescence in the visible region was markedly quenched by various radical trappers and by an inhibitor of NADPH-cytochrome c reductase, but not by superoxide dismutase. During the early stage of lipid peroxidation, the intensity of chemiluminescence was proportional to the square of the concentration of lipid peroxide. These characteristics suggest that singlet oxygen and a compound in the triplet state (probably a carbonyl compound) are generated by a self-reaction of lipid peroxy radicals."}
{"id": "PMID:2318", "title": "Primary reactions of photosystem II at low pH. I. Prompt and delayed fluorescence.", "content": "Prompt and delayed chlorophyll fluorescence have been studied in broken spinach chloroplasts at pH values down to 2.6. No direct effect of low pH on the primary charge separation in Photosystem II was observed. The irreversible inactivation of a secondary electron donor in a narrow pH range around pH 4.5 was demonstrated. At lower pH values the photooxidized form of a more primary electron donor, revealed by its efficient fluorescence quenching, was reduced with a half time of about 200 mus, 25% by another electron donor and 75% by back reaction with the reduced acceptor. The electron donation had a half time of 800 mus and was practically irreversible. The back reaction had a pH dependent half time: about 270 mus at pH 4 and increasing towards lower pH. The competition of both reactions resulted in a net efficiency of the charge separation at pH 4 of 25%, increasing towards lower pH.", "contents": "Primary reactions of photosystem II at low pH. I. Prompt and delayed fluorescence. Prompt and delayed chlorophyll fluorescence have been studied in broken spinach chloroplasts at pH values down to 2.6. No direct effect of low pH on the primary charge separation in Photosystem II was observed. The irreversible inactivation of a secondary electron donor in a narrow pH range around pH 4.5 was demonstrated. At lower pH values the photooxidized form of a more primary electron donor, revealed by its efficient fluorescence quenching, was reduced with a half time of about 200 mus, 25% by another electron donor and 75% by back reaction with the reduced acceptor. The electron donation had a half time of 800 mus and was practically irreversible. The back reaction had a pH dependent half time: about 270 mus at pH 4 and increasing towards lower pH. The competition of both reactions resulted in a net efficiency of the charge separation at pH 4 of 25%, increasing towards lower pH."}
{"id": "PMID:2319", "title": "Immunological similarity between NADH-cytochrome b5 reductase of erythrocytes and liver microsomes.", "content": "In a number of animal species soluble NADH-cytochrome b5 reductase of erythrocytes was compared with membrane-bound NADH-cytochrome b5 reductase of liver microsomes by using an antibody to purified NADH-cytochrome b5 reductase from rat liver microsomes. The results obtained indicated clearly that they are immunologically very similar to each other. The data with erythrocyte ghosts suggested that cytochrome b5 and NADH-cytochrome b5 reductase are also present in the ghost.", "contents": "Immunological similarity between NADH-cytochrome b5 reductase of erythrocytes and liver microsomes. In a number of animal species soluble NADH-cytochrome b5 reductase of erythrocytes was compared with membrane-bound NADH-cytochrome b5 reductase of liver microsomes by using an antibody to purified NADH-cytochrome b5 reductase from rat liver microsomes. The results obtained indicated clearly that they are immunologically very similar to each other. The data with erythrocyte ghosts suggested that cytochrome b5 and NADH-cytochrome b5 reductase are also present in the ghost."}
{"id": "PMID:2320", "title": "Effect of NADP on light-induced cytochrome changes in membrane fragments from a blue-green alga.", "content": "The effect of NADP+ on light-induced steady-state redox changes of membrane-bound cytochromes was investigated in membrane fragements prepared from the blue-green algae Nostoc muscorum (Strain 7119) that had high rates of electron transport from water to NADP+ and from an artificial electron donor, reduced dichlorophenolindophenol (DCIPH2) to NDAP+. The membrane fragments contained very little phycocyanin and had excellent optical properties for spectrophotometric assays. With DCIPH2 as the electron donor, NADP+ had no effect on the light-induced redox changes of cytochromes: with or without NADP+, 715- or 664-nm illumination resulted mainly in the oxidation of cytochrome f and of other component(s) which may include a c-type cytochrome with an alpha peak at 549nm. With 664 nm illumination and water as the electron donor, NADP+ had a pronounced effect on the redox state of cytochromes, causing a shift toward oxidation of a component with a peak at 549 nm (possibly a c-type cytochrome), cytochrome f, and particularly cytochrome b559. Cytochrome b559 appeared to be a component of the main noncyclic electron transport chain and was photooxidized at physiological temperatures by Photosystem II. This photooxidation was apparent only in the presence of a terminal acceptor (NADP+) for the electron flow from water.", "contents": "Effect of NADP on light-induced cytochrome changes in membrane fragments from a blue-green alga. The effect of NADP+ on light-induced steady-state redox changes of membrane-bound cytochromes was investigated in membrane fragements prepared from the blue-green algae Nostoc muscorum (Strain 7119) that had high rates of electron transport from water to NADP+ and from an artificial electron donor, reduced dichlorophenolindophenol (DCIPH2) to NDAP+. The membrane fragments contained very little phycocyanin and had excellent optical properties for spectrophotometric assays. With DCIPH2 as the electron donor, NADP+ had no effect on the light-induced redox changes of cytochromes: with or without NADP+, 715- or 664-nm illumination resulted mainly in the oxidation of cytochrome f and of other component(s) which may include a c-type cytochrome with an alpha peak at 549nm. With 664 nm illumination and water as the electron donor, NADP+ had a pronounced effect on the redox state of cytochromes, causing a shift toward oxidation of a component with a peak at 549 nm (possibly a c-type cytochrome), cytochrome f, and particularly cytochrome b559. Cytochrome b559 appeared to be a component of the main noncyclic electron transport chain and was photooxidized at physiological temperatures by Photosystem II. This photooxidation was apparent only in the presence of a terminal acceptor (NADP+) for the electron flow from water."}
{"id": "PMID:2321", "title": "Kinetic studies on cytochrome c oxidase by combined epr and reflectance spectroscopy after rapid freezing.", "content": "1. Techniques and experiments are described concerned with the millisecond kinetics of EPT-detectable changes brought about in cytochrome c oxidase by reduced cytochrome c and, after reduction with various agents, by reoxidation with O2 or ferricyanide. Some experiments in the presence of ligands are also reported. Light absorption was monitored by low-temperature reflectance spectroscopy. 2. In the rapid phase of reduction of cytochrome c oxidase by cytochrome c (less than 50 ms) approx. 0.5 electron equivalent per heme a is transferred mainly to the low-spin heme component of cytochrome c oxidase and partly to the EPR-detectable copper. In a slow phase (less than 1 s) the copper is reoxidized and high-spin ferric heme signals appear with a predominant rhombic component. Simultaneously the absorption band at 655 nm decreases and the Soret band at 444 nm appears between the split Soret band (442 and 447 nm) of reduced cytochrome a. 3. On reoxidation of reduced enzyme by oxygen all EPR and optical features are restored within 6 ms. On reoxidation by O2 in the presence of an excess of reduced cytochrome c, states can be observed where the low-spin heme and copper signals are largely absent but the absorption at 655 nm is maximal, indicating that the low-spin heme and copper components are at the substrate side and the component(s) represented in the 655 nm absorption at the O2 side of the system. On reoxidation with ferricyanide the 655 nm absorption is not readily restored but a ferric high-spin heme, represented by a strong rhombic signal, accumulates. 4. On reoxidation of partly reduced enzyme by oxygen, the rhombic high-spin signals disappear within 6 ms., whereas the axial signals disappear more slowly, indicating that these species are not in rapid equilibrium. Similar observations are made when partly reduced enzyme is mixed with CO. 5. The results of this and the accompanying paper are discussed and on this basis an assignment of the major EPR signals and of the 655 nm absorption is proposed, which in essence is that published previously (Hartzell, C.R., Hansen, R.E. and Beinert, H. (1973) Proc. Natl. Acad. Sci. U.S. 70, 2477-2481). Both the low-spin (g=o; 2.2; 1.5) and slowly appearing high-spin (g=6; 2) signals are attributed to ferric cytochrome a, whereas the 655 nm absorption is thought to arise from ferric cytochrome a3, when it is present in a state of interaction with EPR-undectectable copper. Alternative possibilities and possible inconsistencies with this proposal are discussed.", "contents": "Kinetic studies on cytochrome c oxidase by combined epr and reflectance spectroscopy after rapid freezing. 1. Techniques and experiments are described concerned with the millisecond kinetics of EPT-detectable changes brought about in cytochrome c oxidase by reduced cytochrome c and, after reduction with various agents, by reoxidation with O2 or ferricyanide. Some experiments in the presence of ligands are also reported. Light absorption was monitored by low-temperature reflectance spectroscopy. 2. In the rapid phase of reduction of cytochrome c oxidase by cytochrome c (less than 50 ms) approx. 0.5 electron equivalent per heme a is transferred mainly to the low-spin heme component of cytochrome c oxidase and partly to the EPR-detectable copper. In a slow phase (less than 1 s) the copper is reoxidized and high-spin ferric heme signals appear with a predominant rhombic component. Simultaneously the absorption band at 655 nm decreases and the Soret band at 444 nm appears between the split Soret band (442 and 447 nm) of reduced cytochrome a. 3. On reoxidation of reduced enzyme by oxygen all EPR and optical features are restored within 6 ms. On reoxidation by O2 in the presence of an excess of reduced cytochrome c, states can be observed where the low-spin heme and copper signals are largely absent but the absorption at 655 nm is maximal, indicating that the low-spin heme and copper components are at the substrate side and the component(s) represented in the 655 nm absorption at the O2 side of the system. On reoxidation with ferricyanide the 655 nm absorption is not readily restored but a ferric high-spin heme, represented by a strong rhombic signal, accumulates. 4. On reoxidation of partly reduced enzyme by oxygen, the rhombic high-spin signals disappear within 6 ms., whereas the axial signals disappear more slowly, indicating that these species are not in rapid equilibrium. Similar observations are made when partly reduced enzyme is mixed with CO. 5. The results of this and the accompanying paper are discussed and on this basis an assignment of the major EPR signals and of the 655 nm absorption is proposed, which in essence is that published previously (Hartzell, C.R., Hansen, R.E. and Beinert, H. (1973) Proc. Natl. Acad. Sci. U.S. 70, 2477-2481). Both the low-spin (g=o; 2.2; 1.5) and slowly appearing high-spin (g=6; 2) signals are attributed to ferric cytochrome a, whereas the 655 nm absorption is thought to arise from ferric cytochrome a3, when it is present in a state of interaction with EPR-undectectable copper. Alternative possibilities and possible inconsistencies with this proposal are discussed."}
{"id": "PMID:2322", "title": "Some thermodynamic and kinetic properties of the primary photochemical reactants in a complex from a green photosynthetic bacterium.", "content": "We have examined the bacteriochlorophyll reaction-center complex of Chlorobium limicola f. thiosulfatophilum, strain Tassajara. Our results indicate that the midpoint potential of the primary electron donor bacteriochlorophyll of the reaction center is +250 mV at pH 6.8, while that of cytochrome c-553 is +165 mV. There are two cytochrome c-553 hemes per reaction center, and the light-induced oxidation of each is biphasic (t1/2 of less than 5 mus and approximately 50 mus). We belive that this indicates a two state equilibrium with each cytochrome heme being either close to, or a little removed from, the reaction-center bacteriochlorophyll. We have also titrated the primary electron acceptor of the reaction center. Its equilibrium midpoint potential at pH 6.8 is below -450 mV. This is very much lower than the previous estimate for green bacteria, and also substantially lower than values obtained for purple bacteria. Such a low-potential primary acceptor would be thermodynamically capable of direct reduction of NAD+ via ferredoxin in a manner analagous to photosystem I in chloroplasts and blue-green algae.", "contents": "Some thermodynamic and kinetic properties of the primary photochemical reactants in a complex from a green photosynthetic bacterium. We have examined the bacteriochlorophyll reaction-center complex of Chlorobium limicola f. thiosulfatophilum, strain Tassajara. Our results indicate that the midpoint potential of the primary electron donor bacteriochlorophyll of the reaction center is +250 mV at pH 6.8, while that of cytochrome c-553 is +165 mV. There are two cytochrome c-553 hemes per reaction center, and the light-induced oxidation of each is biphasic (t1/2 of less than 5 mus and approximately 50 mus). We belive that this indicates a two state equilibrium with each cytochrome heme being either close to, or a little removed from, the reaction-center bacteriochlorophyll. We have also titrated the primary electron acceptor of the reaction center. Its equilibrium midpoint potential at pH 6.8 is below -450 mV. This is very much lower than the previous estimate for green bacteria, and also substantially lower than values obtained for purple bacteria. Such a low-potential primary acceptor would be thermodynamically capable of direct reduction of NAD+ via ferredoxin in a manner analagous to photosystem I in chloroplasts and blue-green algae."}
{"id": "PMID:2323", "title": "Reaction of uracil and thymine derivatives with sodium bisulfite. Studies on the mechanism and reduction of the adduct.", "content": "The rates and equilibria for the addition of sodium bisulfite to uracil, thymine, and their nucleosides have been studied for the pH range 3-9.5. The rate of addition for uracil is proportional to the concentration of sulfite ion and unionized uracil. The equilibrium constant (25 degrees C) for the reaction is (1.0 +/- 0.15) X 10(3) 1 - mol-1 for uracil and 0.62 +/- 0.03 1- mol-1 for thymine. A pH of 6-7, with a high bisulfite concentration is suggested for biochemical applications of the uracil reaction. The uracil reaction, which proceeds readily under physiological conditions and has a high equilibrium constant, may be a contributing cause of the biochemical effects of bisulfite and sulfur dioxide. Additional evidence on the structure of the thymine-bisulfite adduct has been obtained by nuclear magnetic resonance spectroscopy. This spectrum supports the assignment of structure as dihydrothymine-6-sulfonate. The uracil-bisulfite adduct is reduced by sodium borohydride to sodium 3-ureido-propanol-2-sulfonate. This reaction is suggested for the chemical modification of nucleic acids.", "contents": "Reaction of uracil and thymine derivatives with sodium bisulfite. Studies on the mechanism and reduction of the adduct. The rates and equilibria for the addition of sodium bisulfite to uracil, thymine, and their nucleosides have been studied for the pH range 3-9.5. The rate of addition for uracil is proportional to the concentration of sulfite ion and unionized uracil. The equilibrium constant (25 degrees C) for the reaction is (1.0 +/- 0.15) X 10(3) 1 - mol-1 for uracil and 0.62 +/- 0.03 1- mol-1 for thymine. A pH of 6-7, with a high bisulfite concentration is suggested for biochemical applications of the uracil reaction. The uracil reaction, which proceeds readily under physiological conditions and has a high equilibrium constant, may be a contributing cause of the biochemical effects of bisulfite and sulfur dioxide. Additional evidence on the structure of the thymine-bisulfite adduct has been obtained by nuclear magnetic resonance spectroscopy. This spectrum supports the assignment of structure as dihydrothymine-6-sulfonate. The uracil-bisulfite adduct is reduced by sodium borohydride to sodium 3-ureido-propanol-2-sulfonate. This reaction is suggested for the chemical modification of nucleic acids."}
{"id": "PMID:2324", "title": "Intramembrane particle aggregation in erythrocyte ghosts. II. The influence of spectrin aggregation.", "content": "Physicochemical properties of mixtures of spectrin and actin extracted from human erythrocyte ghosts have been correlated with ultrastructural changes observed in freeze-fractured erythrocyte membranes. (1) Extracted mixtures of spectrin and actin have a very low solubility (less than 30 mug/ml) near their isoelectric point, pH 4.8. These mixtures are also precipitated by low concentrations of Ca2+, Mg2+, polylysine or basic proteins. (2) All conditions which precipitate extracts of spectrin and actin also induce aggregation of the intramembrane particles in spectrin-depleted erythrocyte ghosts. Precipitation of the residual spectrin molecules into small patches on the cytoplasmic surface of the ghost membrane is thought to be the cause of particle aggregations, implying an association between the spectrin molecules and the intramembrane particles. (3) When fresh ghosts are exposed to conditions which precipitate extracts of spectrin and actin, only limited particle aggregation occurs. Instead, the contraction of the intact spectrin meshwork induced by the precipitation conditions compresses the lipid bilayer of the membrane, causing it to bleb off particle-free, protein-free vesicles. (4) The absence of protein in these lipid vesicles implies that all the proteins of the erythrocyte membrane are immobilized by association with either the spectrin meshwork or the intramembrane particles.", "contents": "Intramembrane particle aggregation in erythrocyte ghosts. II. The influence of spectrin aggregation. Physicochemical properties of mixtures of spectrin and actin extracted from human erythrocyte ghosts have been correlated with ultrastructural changes observed in freeze-fractured erythrocyte membranes. (1) Extracted mixtures of spectrin and actin have a very low solubility (less than 30 mug/ml) near their isoelectric point, pH 4.8. These mixtures are also precipitated by low concentrations of Ca2+, Mg2+, polylysine or basic proteins. (2) All conditions which precipitate extracts of spectrin and actin also induce aggregation of the intramembrane particles in spectrin-depleted erythrocyte ghosts. Precipitation of the residual spectrin molecules into small patches on the cytoplasmic surface of the ghost membrane is thought to be the cause of particle aggregations, implying an association between the spectrin molecules and the intramembrane particles. (3) When fresh ghosts are exposed to conditions which precipitate extracts of spectrin and actin, only limited particle aggregation occurs. Instead, the contraction of the intact spectrin meshwork induced by the precipitation conditions compresses the lipid bilayer of the membrane, causing it to bleb off particle-free, protein-free vesicles. (4) The absence of protein in these lipid vesicles implies that all the proteins of the erythrocyte membrane are immobilized by association with either the spectrin meshwork or the intramembrane particles."}
{"id": "PMID:2325", "title": "The rate of calcium uptake into sarcoplasmic reticulum of cardiac muscle and skeletal muscle. Effects of cyclic AMP-dependent protein kinase and phosphorylase b kinase.", "content": "Calcium transport into sarcoplasmic reticulum fragments isolated from dog cardiac and mixed skeletal muscle (quadriceps) and from mixed fast (tibialis), pure fast (caudofemoralis) and pure slow (soleus) skeletal muscles from the cat was studied. Cyclic AMP-dependent protein kinase and phosphorylase b kinase stimulated the rate of calcium transport although some variability was observed. A specific protein kinase inhibitor prevented the effect of protein kinase but not of phosphorylase b kinase. The addition of cyclic AMP to the sarcoplasmic reticulum preparations in the absence of protein kinase had only a slight stimulatory effect despite the presence of endogenous protein kinase. Cyclic AMP-dependent protein kinase catalyzed the phosphorylation of several components present in the sarcoplasmic reticulum fragments; a 19000 to 21 000 dalton peak was phosphorylated with high specific activity in sarcoplasmic reticulum preparations isolated from heart and from slow skeletal muscle, but not from fast skeletal muscle. Phosphorylase b kinase phosphorylated a peak of molecular weight 95000 in all of the preparations. Cyclic AMP-dependent protein kinase-stimulated phosphorylation was optimum at pH 6.8; phosphorylase b kinase phosphorylation had a biphasic curve in cardiac and slow skeletal muscle with optima at pH 6.8 and 8.0. The addition of exogenous phosphorylase b kinase or protein kinase increased the endogenous level of phosphorylation 25-100%. All sarcoplasmic reticulum preparations contained varying amounts of adenylate cyclase, phosphorylase b and a (b:a = 30.1), \"debrancher\" enzyme and glycogen (0.3 mg/mg protein), as well as varying amounts of protein kinase and phosphorylase b kinase which were responsible for a significant endogenous phosphorylation. Thus, the two phosphorylating enzymes stimulated calcium uptake in the sarcoplasmic reticulum of a variety of muscles possessing different physiologic characteristics and different responses to drugs. In addition, the phosphorylation catalyzed by these enzymes occurred at two different protein moieties which make physiologic interpretation of the role of phosphorylation difficult. While the role phosphorylation in these mechanisms is complex, the presence of a glycogenolytic enzyme system may be an important link in this phenomenon. The sarcoplasmic reticulum represents a new substrate for phosphorylase b kinase.", "contents": "The rate of calcium uptake into sarcoplasmic reticulum of cardiac muscle and skeletal muscle. Effects of cyclic AMP-dependent protein kinase and phosphorylase b kinase. Calcium transport into sarcoplasmic reticulum fragments isolated from dog cardiac and mixed skeletal muscle (quadriceps) and from mixed fast (tibialis), pure fast (caudofemoralis) and pure slow (soleus) skeletal muscles from the cat was studied. Cyclic AMP-dependent protein kinase and phosphorylase b kinase stimulated the rate of calcium transport although some variability was observed. A specific protein kinase inhibitor prevented the effect of protein kinase but not of phosphorylase b kinase. The addition of cyclic AMP to the sarcoplasmic reticulum preparations in the absence of protein kinase had only a slight stimulatory effect despite the presence of endogenous protein kinase. Cyclic AMP-dependent protein kinase catalyzed the phosphorylation of several components present in the sarcoplasmic reticulum fragments; a 19000 to 21 000 dalton peak was phosphorylated with high specific activity in sarcoplasmic reticulum preparations isolated from heart and from slow skeletal muscle, but not from fast skeletal muscle. Phosphorylase b kinase phosphorylated a peak of molecular weight 95000 in all of the preparations. Cyclic AMP-dependent protein kinase-stimulated phosphorylation was optimum at pH 6.8; phosphorylase b kinase phosphorylation had a biphasic curve in cardiac and slow skeletal muscle with optima at pH 6.8 and 8.0. The addition of exogenous phosphorylase b kinase or protein kinase increased the endogenous level of phosphorylation 25-100%. All sarcoplasmic reticulum preparations contained varying amounts of adenylate cyclase, phosphorylase b and a (b:a = 30.1), \"debrancher\" enzyme and glycogen (0.3 mg/mg protein), as well as varying amounts of protein kinase and phosphorylase b kinase which were responsible for a significant endogenous phosphorylation. Thus, the two phosphorylating enzymes stimulated calcium uptake in the sarcoplasmic reticulum of a variety of muscles possessing different physiologic characteristics and different responses to drugs. In addition, the phosphorylation catalyzed by these enzymes occurred at two different protein moieties which make physiologic interpretation of the role of phosphorylation difficult. While the role phosphorylation in these mechanisms is complex, the presence of a glycogenolytic enzyme system may be an important link in this phenomenon. The sarcoplasmic reticulum represents a new substrate for phosphorylase b kinase."}
{"id": "PMID:2326", "title": "[Microcolorimetric study of the association of trypsin with a pancreatic inhibitor].", "content": "Enthalpy of the association of trypsin with pancreatic inhibitor from bovine pancreas at 25 degrees C as a function of pH and ionic strength is estimated. The dependence of the enthalpy on pH is of an extremal character with a minimum at pH 7.6 (delta H degrees =-10.3 ccal/mole). The increase of ionic strength with the addition of LiCl, KCl and CsCl at pH 7.6 leads to be increase of delta H degrees. Possible mechanisms of enthlpy changes depending on medium conditions are considered.", "contents": "[Microcolorimetric study of the association of trypsin with a pancreatic inhibitor]. Enthalpy of the association of trypsin with pancreatic inhibitor from bovine pancreas at 25 degrees C as a function of pH and ionic strength is estimated. The dependence of the enthalpy on pH is of an extremal character with a minimum at pH 7.6 (delta H degrees =-10.3 ccal/mole). The increase of ionic strength with the addition of LiCl, KCl and CsCl at pH 7.6 leads to be increase of delta H degrees. Possible mechanisms of enthlpy changes depending on medium conditions are considered."}
{"id": "PMID:2327", "title": "[Partial purification and properties of protease from Torula thermophila].", "content": "11-Fold purified protease preparation is isolated from cultural medium of Torula thermophila UzPT-1 by means of ammonium sulphate precipitation and gel chromatography through Sephadex G-100. Disc polyacrylamide gel electrophoresis revealed two portease components, one of them possessing proteolytic activity. pH interval for protease activity was found to be 3.5-12, the maximal activity was observed at pH 8.5-11, the highest enzyme resistance--at pH 6-8. The enzyme almost completely preserved its activity for 1 hour in distilled water at 60 degrees C. The temperature maximum of the enzyme activity was 70 degrees at pH 8. The enzyme may be referred to proteases of serine nature, because it is completely inactivated with diisopropylphosphofluoridate, but it retains the activity in the presence of chelating agents (EDTA, o-phenantroline, ditizone) and inhibitors of SH-groups (sodium p-chloromercuriumbenzoate, iodoacetic acid). The enzyme was not inactivated with phenylmethylsulphonylfluoride and the trypsin inhibitor from soybean. The protease studied most efficiently hydrolyzed caseine and hemoglobin, in a less degree--human serum albumin and fibrinogen and almost did not attack egg albumin. The enzyme undergoes association-dissociation under pH change during gel filtration through Sephadex.", "contents": "[Partial purification and properties of protease from Torula thermophila]. 11-Fold purified protease preparation is isolated from cultural medium of Torula thermophila UzPT-1 by means of ammonium sulphate precipitation and gel chromatography through Sephadex G-100. Disc polyacrylamide gel electrophoresis revealed two portease components, one of them possessing proteolytic activity. pH interval for protease activity was found to be 3.5-12, the maximal activity was observed at pH 8.5-11, the highest enzyme resistance--at pH 6-8. The enzyme almost completely preserved its activity for 1 hour in distilled water at 60 degrees C. The temperature maximum of the enzyme activity was 70 degrees at pH 8. The enzyme may be referred to proteases of serine nature, because it is completely inactivated with diisopropylphosphofluoridate, but it retains the activity in the presence of chelating agents (EDTA, o-phenantroline, ditizone) and inhibitors of SH-groups (sodium p-chloromercuriumbenzoate, iodoacetic acid). The enzyme was not inactivated with phenylmethylsulphonylfluoride and the trypsin inhibitor from soybean. The protease studied most efficiently hydrolyzed caseine and hemoglobin, in a less degree--human serum albumin and fibrinogen and almost did not attack egg albumin. The enzyme undergoes association-dissociation under pH change during gel filtration through Sephadex."}
{"id": "PMID:2328", "title": "[Various properties of the creatine transport system and the location of creatine kinase in skeletal muscle mitochondria].", "content": "Water and creatine contents were studied in rat skeletal muscle mitochondria after their 5 min. incubation in creatine solutions, pH 7.2 or 8.4. The content of water and creatine in mitochondria was found to be higher at pH 8.4, than at pH 72, the creatine content correlated with the water content. Structural creatine analogues, containing aminogroups with pKa greater than or equal to 9.5 or carboxyl groups, inhibited the infusion of creatine into mitochondria more strongly than substances having aminogroups with pKa less than 5. The penetrating form is creatine amphiion; the effect of pH on the permeability is probably due to the activation of the creatine transmitter. Rat skeletal muscle mitochondria contain creatine kinase at both sides of the inner membrane. This conclusion is based on the fact that under conditions, supplying the direct course of the creatine kinase reaction (the incubation medium contains Ca2+ and creatine; pH 7.8), ADP produces the stimulation of mitochondrial respiration up to the oxygen exhausting in a polarographic unit. Similarly, ADP irreversibly stimulates mitochondrial respiration in the presence of 1 mM EDTA, if EDTA and ADP are added after the preincubation of mitochondria in creatine-containing medium and after accumulating small amounts of Ca2+ by mitochondria.", "contents": "[Various properties of the creatine transport system and the location of creatine kinase in skeletal muscle mitochondria]. Water and creatine contents were studied in rat skeletal muscle mitochondria after their 5 min. incubation in creatine solutions, pH 7.2 or 8.4. The content of water and creatine in mitochondria was found to be higher at pH 8.4, than at pH 72, the creatine content correlated with the water content. Structural creatine analogues, containing aminogroups with pKa greater than or equal to 9.5 or carboxyl groups, inhibited the infusion of creatine into mitochondria more strongly than substances having aminogroups with pKa less than 5. The penetrating form is creatine amphiion; the effect of pH on the permeability is probably due to the activation of the creatine transmitter. Rat skeletal muscle mitochondria contain creatine kinase at both sides of the inner membrane. This conclusion is based on the fact that under conditions, supplying the direct course of the creatine kinase reaction (the incubation medium contains Ca2+ and creatine; pH 7.8), ADP produces the stimulation of mitochondrial respiration up to the oxygen exhausting in a polarographic unit. Similarly, ADP irreversibly stimulates mitochondrial respiration in the presence of 1 mM EDTA, if EDTA and ADP are added after the preincubation of mitochondria in creatine-containing medium and after accumulating small amounts of Ca2+ by mitochondria."}
{"id": "PMID:2329", "title": "[Isolation and properties of a homogeneous L-asparaginase preparation from Pseudomonas fluorescens AG].", "content": "Highly purified L-asparaginase having a specific activity of 500+/- +/-40 IU./mg protein is isolated from Pseudomonas fluorescens AG cells. The purification procedure includes isopropanol fractionation, gel filtration through Sephadex G-100, chromatography on hydroxylapatite and DEAE-cellulose columns. The asparaginase preparation is homogenous on the basis of polyacrylamide gel electrophoresis data. The pH optimum is found to be 8.0-9.0, isoelectric point and molecular weight are 4.5+/-0.05 and 70,000+/-5,000 respectively, Km for L-asparagine being-4.1-10(-4)M. The enzyme does not hydrolyse L-glutamine. The hydrolysis rate of D-glutamine is less than 1% of the deamydation rate of L-isomer. p-Chloro-mercurium benzoate at a concentration of 10(-4) M completely inhibits the asparaginase activity. Asparaginase from Ps. fluorescens AG possesses and antileucosic activity, inhibiting 3H-thymidine incorporation into DNA of Berkit lymphoma cells.", "contents": "[Isolation and properties of a homogeneous L-asparaginase preparation from Pseudomonas fluorescens AG]. Highly purified L-asparaginase having a specific activity of 500+/- +/-40 IU./mg protein is isolated from Pseudomonas fluorescens AG cells. The purification procedure includes isopropanol fractionation, gel filtration through Sephadex G-100, chromatography on hydroxylapatite and DEAE-cellulose columns. The asparaginase preparation is homogenous on the basis of polyacrylamide gel electrophoresis data. The pH optimum is found to be 8.0-9.0, isoelectric point and molecular weight are 4.5+/-0.05 and 70,000+/-5,000 respectively, Km for L-asparagine being-4.1-10(-4)M. The enzyme does not hydrolyse L-glutamine. The hydrolysis rate of D-glutamine is less than 1% of the deamydation rate of L-isomer. p-Chloro-mercurium benzoate at a concentration of 10(-4) M completely inhibits the asparaginase activity. Asparaginase from Ps. fluorescens AG possesses and antileucosic activity, inhibiting 3H-thymidine incorporation into DNA of Berkit lymphoma cells."}
{"id": "PMID:2330", "title": "[Analysis of sheep blood serum haptoglobin].", "content": "Three types of haptoglobin (Hp), differing in the number of bands of Hp--Hb complex on polyacrylamide gel electrophoregramm are found in sheep blood serum. HpA, HpB and HpC fractions included one, two-three and six-eight bands respectively. A modified procedure for the HpC isolation is described. Effects of urea, sodium dodecylsulpate, beta-mercaptoethanol, pH and maleinization on the behaviour of HpC under polyacrylamide gel electrophoresis is studied. The data obtained suggest that the HpC molecule consists of two subunits (of alpha and beta types), bound with S--S bounds in an alphabeta-dimer, which form a whole HpC molecule for the expense of non-covalent bonds.", "contents": "[Analysis of sheep blood serum haptoglobin]. Three types of haptoglobin (Hp), differing in the number of bands of Hp--Hb complex on polyacrylamide gel electrophoregramm are found in sheep blood serum. HpA, HpB and HpC fractions included one, two-three and six-eight bands respectively. A modified procedure for the HpC isolation is described. Effects of urea, sodium dodecylsulpate, beta-mercaptoethanol, pH and maleinization on the behaviour of HpC under polyacrylamide gel electrophoresis is studied. The data obtained suggest that the HpC molecule consists of two subunits (of alpha and beta types), bound with S--S bounds in an alphabeta-dimer, which form a whole HpC molecule for the expense of non-covalent bonds."}
{"id": "PMID:2331", "title": "[Reaction ability and alkylation kinetics of sulfhydride groups of soluble succinate dehydrogenase].", "content": "Inhibition kinetics of succinate--an acceptor of oxidoreductase activity of soluble succinate dehydrogenase by N-ethylmaleimide is studied. The alkylation reaction is described by the kinetic equation of the first order, its stechiometric coefficient being 1. The binding of enzyme sulphhydride groups by p-chloromercuriumbenzoate blocks the enzyme alkylation and its inhibition by oxaloacetate. Succinate protects succinate dehydrogenase from the inhibitory effect of N-ethylmaleimide. The reaction of the enzyme with an alkylating agent in the presence of different substrate concentrations corresponds kinetically to the model, according to which a sulphhydride group acts in the active site of the enzyme. pKa of this group is 7.0 at 20degreesC. The dependency of the maximal substrate oxidation reaction rate and that of the enzyme alkylation rate on pH coinside at the pH range 5.8--7.8. The presence of anions in the alkylation medium decreases the reaction ability of the active site with respect to N-ethylmaleimide. A mechanism of the initial stage of succinate oxidation with the cooperation of the sulphhydride group of the enzyme active site is postulated.", "contents": "[Reaction ability and alkylation kinetics of sulfhydride groups of soluble succinate dehydrogenase]. Inhibition kinetics of succinate--an acceptor of oxidoreductase activity of soluble succinate dehydrogenase by N-ethylmaleimide is studied. The alkylation reaction is described by the kinetic equation of the first order, its stechiometric coefficient being 1. The binding of enzyme sulphhydride groups by p-chloromercuriumbenzoate blocks the enzyme alkylation and its inhibition by oxaloacetate. Succinate protects succinate dehydrogenase from the inhibitory effect of N-ethylmaleimide. The reaction of the enzyme with an alkylating agent in the presence of different substrate concentrations corresponds kinetically to the model, according to which a sulphhydride group acts in the active site of the enzyme. pKa of this group is 7.0 at 20degreesC. The dependency of the maximal substrate oxidation reaction rate and that of the enzyme alkylation rate on pH coinside at the pH range 5.8--7.8. The presence of anions in the alkylation medium decreases the reaction ability of the active site with respect to N-ethylmaleimide. A mechanism of the initial stage of succinate oxidation with the cooperation of the sulphhydride group of the enzyme active site is postulated."}
{"id": "PMID:2332", "title": "[Effect of IAA on the photophosphorylation of pea isolated chloroplasts].", "content": "Effect of IAA (10(-10)-10(-3) M) on photophosphorylation, NADP reduction and the oxygen exchange is investigated. It is shown that low concentrations of IAA (10(-10)-10(-7) M) increase the photophosphorylation reaction and the flow of electrones to NADP under the phosphorylation conditions in the chloroplasts, and their effect on the O2 exchange is not the same in different types of photophosphorylation. It is supposed that the effect of IAA on the photophosphorylation is connected with H292 metabolism in chloroplasts and with catalase and peroxidase functions.", "contents": "[Effect of IAA on the photophosphorylation of pea isolated chloroplasts]. Effect of IAA (10(-10)-10(-3) M) on photophosphorylation, NADP reduction and the oxygen exchange is investigated. It is shown that low concentrations of IAA (10(-10)-10(-7) M) increase the photophosphorylation reaction and the flow of electrones to NADP under the phosphorylation conditions in the chloroplasts, and their effect on the O2 exchange is not the same in different types of photophosphorylation. It is supposed that the effect of IAA on the photophosphorylation is connected with H292 metabolism in chloroplasts and with catalase and peroxidase functions."}
{"id": "PMID:2333", "title": "[Purification, molecular multiplicity and kinetic properties of \"biosynthetic\" L-threonine dehydratase from E. coli K-12].", "content": "\"Biosynthetic\" L-threonine dehydratase was purified to homogeneous state with yield 29% of total activity from E. coli K-12. The cells were disrupted by means of ultra sound. Nucleic acids and nucleoproteins were precipitated with protamine sulphate, the proteins were fractioned with (NH4)2SO4, by gel filtration through Sephadex G-25 followed by chromatography on DEAE-cellulose using stepways elution by changing the pH-values. The homogenity of the enzyme was shown by polyacrylamide gel disc electrophoresis in the presence of dodecylsulphate. The enzyme consists of equal subunits having a molecular weight about 57000. The polyacrylamide gel disc electrophoresis had shown that the native enzyme consists of a set of oligomeric forms. The multiplisity of molecular organization of the enzyme was relfected in complicated kinetic behavior: at pH greater than 9 on the plots of initial reaction rate (upsilon) versus initial substrate concentration ([S]0) there were four inflexion points (two intermediate plateaux) the position and deepness of which depended on enzyme concentration. Kinetic properties of the highly purified enzyme and the enzyme in crude cell extracts at pH 9.3 and 7.4 were identical. At pH 8,3 on the upsilon versus [S]0 plots appeared two inflexion points (one intermediate plateau), the position of which practically did not depend on enzyme concentration in the reaction mixture but strongly depended on the enzyme concentration in the stock solution. Repeated polyacrylamide gel disc electrophoresis of several oligomeric forms isolated by the first electrophoresis had shown that oligomeric forms underwent a slow polymerization. It is suggested that \"biosynthetic\" L-threonine dehydratase from E. coli K-12 is a set of multiple oligomeric forms having different kinetic parameters. Probably, each form of the enzyme has a \"simple\" kinetics characterized by hyperbolic or sigmoidal shape of upsilon versus [S]0 plots. The rate of equilibrium between the oligomeric forms is small in comparison with the enzyme reaction velosity, that lead to the complex kinetic curves appearing as a result of summing up the kinetics inherent to the individual forms.", "contents": "[Purification, molecular multiplicity and kinetic properties of \"biosynthetic\" L-threonine dehydratase from E. coli K-12]. \"Biosynthetic\" L-threonine dehydratase was purified to homogeneous state with yield 29% of total activity from E. coli K-12. The cells were disrupted by means of ultra sound. Nucleic acids and nucleoproteins were precipitated with protamine sulphate, the proteins were fractioned with (NH4)2SO4, by gel filtration through Sephadex G-25 followed by chromatography on DEAE-cellulose using stepways elution by changing the pH-values. The homogenity of the enzyme was shown by polyacrylamide gel disc electrophoresis in the presence of dodecylsulphate. The enzyme consists of equal subunits having a molecular weight about 57000. The polyacrylamide gel disc electrophoresis had shown that the native enzyme consists of a set of oligomeric forms. The multiplisity of molecular organization of the enzyme was relfected in complicated kinetic behavior: at pH greater than 9 on the plots of initial reaction rate (upsilon) versus initial substrate concentration ([S]0) there were four inflexion points (two intermediate plateaux) the position and deepness of which depended on enzyme concentration. Kinetic properties of the highly purified enzyme and the enzyme in crude cell extracts at pH 9.3 and 7.4 were identical. At pH 8,3 on the upsilon versus [S]0 plots appeared two inflexion points (one intermediate plateau), the position of which practically did not depend on enzyme concentration in the reaction mixture but strongly depended on the enzyme concentration in the stock solution. Repeated polyacrylamide gel disc electrophoresis of several oligomeric forms isolated by the first electrophoresis had shown that oligomeric forms underwent a slow polymerization. It is suggested that \"biosynthetic\" L-threonine dehydratase from E. coli K-12 is a set of multiple oligomeric forms having different kinetic parameters. Probably, each form of the enzyme has a \"simple\" kinetics characterized by hyperbolic or sigmoidal shape of upsilon versus [S]0 plots. The rate of equilibrium between the oligomeric forms is small in comparison with the enzyme reaction velosity, that lead to the complex kinetic curves appearing as a result of summing up the kinetics inherent to the individual forms."}
{"id": "PMID:2334", "title": "[Purification and some properties of electrophoretic variants of 6-phosphogluconate dehydrogenase from rat erythrocytes].", "content": "Purification procedure of electrophoretic variants FF and SS of 6-phosphogluconate dehydrogenase (6-PGD) is described. The method includes (NH4)2SO4 fractionation and chromatography on DEAE- and CM-celluloses. Isoenzymes were purified about 5000 fold, and were found to be homogenous by disc electrophoresis in 7% polyacrylamide gel. It was found by comparative studies of activities of variants FF and SS, that pH optimum was 8.2 for variant FF and 8.8 for variant SS. Km for 6-phosphogluconate were found to be 17,5-10(-5) M for variants SS and FF respectively.", "contents": "[Purification and some properties of electrophoretic variants of 6-phosphogluconate dehydrogenase from rat erythrocytes]. Purification procedure of electrophoretic variants FF and SS of 6-phosphogluconate dehydrogenase (6-PGD) is described. The method includes (NH4)2SO4 fractionation and chromatography on DEAE- and CM-celluloses. Isoenzymes were purified about 5000 fold, and were found to be homogenous by disc electrophoresis in 7% polyacrylamide gel. It was found by comparative studies of activities of variants FF and SS, that pH optimum was 8.2 for variant FF and 8.8 for variant SS. Km for 6-phosphogluconate were found to be 17,5-10(-5) M for variants SS and FF respectively."}
{"id": "PMID:2335", "title": "[Comparative study of glutamate dehydrogenases of Chlorella].", "content": "The kinetic properties of the constitutive double specific glutamate dehydrogenase (NAD(P)--GDH) and the inducible NADP-specific glutamate dehydrogenase (NADP--GDH) of Chlorella pyrenoidosa Pringsheim 82T (thermophilic strain) in a deaminating reaction have been studied. NAD(P)-GDH behaves in a deamination as a Michaelis-Menten enzyme. NADP-GDH displays some lag-period before a steady-state phase. The duration of this lag depends on a substrate concentration. Besides that, an effect of all the substrates on a heat inactivation of both GDH and a product inhibition have been studied. All the substrates except the reduced co-factors protect effectively GDH from the heat inactivation, especially the thermolabille NADP-GDH. On the contrary, NAD(P)-H promote the heat inactivation of both GDH. The product inhibition analysis shows that the inducible NADP-GDH acts in vivo as a synthetic enzyme. In the previous paper (V. R. Shatilov et all., 1974, Dokl. Acad. Nauk USSR, 216,223) it was shown for the constitutive GDH that p-CMB strongly inhibited a desamination and slightly (if any) affect an amination. It this paper it is shown that action of p-CMB on the amination depends on the presence of NAD+ (not NADP+ or L-glutamate). p-CMB and NAD+ affect tha amination in a strongly sunergetic manner. Some suggestions about the intracellular localization of chlorella GDH are made.", "contents": "[Comparative study of glutamate dehydrogenases of Chlorella]. The kinetic properties of the constitutive double specific glutamate dehydrogenase (NAD(P)--GDH) and the inducible NADP-specific glutamate dehydrogenase (NADP--GDH) of Chlorella pyrenoidosa Pringsheim 82T (thermophilic strain) in a deaminating reaction have been studied. NAD(P)-GDH behaves in a deamination as a Michaelis-Menten enzyme. NADP-GDH displays some lag-period before a steady-state phase. The duration of this lag depends on a substrate concentration. Besides that, an effect of all the substrates on a heat inactivation of both GDH and a product inhibition have been studied. All the substrates except the reduced co-factors protect effectively GDH from the heat inactivation, especially the thermolabille NADP-GDH. On the contrary, NAD(P)-H promote the heat inactivation of both GDH. The product inhibition analysis shows that the inducible NADP-GDH acts in vivo as a synthetic enzyme. In the previous paper (V. R. Shatilov et all., 1974, Dokl. Acad. Nauk USSR, 216,223) it was shown for the constitutive GDH that p-CMB strongly inhibited a desamination and slightly (if any) affect an amination. It this paper it is shown that action of p-CMB on the amination depends on the presence of NAD+ (not NADP+ or L-glutamate). p-CMB and NAD+ affect tha amination in a strongly sunergetic manner. Some suggestions about the intracellular localization of chlorella GDH are made."}
{"id": "PMID:2336", "title": "[Fibril formation in solutions of solubilized collagen].", "content": "Influence of the preparations of bacterial proteinases, protorisine and prototerrisine, was studied on the stability of the mature collagen of beef skin. The chemical composition of the tissue has been shown to be changed by these enzymes inconsiderably. The tissue treated by orisine and terrisine is completely dissolved in 0.5 M acetic acid (solubilized collagen). When the solutions of such collagen are heated to 37 degrees within the pH range from 4 to 10 at the ionic strength of 0.25 fibrils are formed. Under electron microscope fibres are cross-striated that is typical of native collagen fibres with periodicity of about 640 A. After chilling to 4 degrees, a part of fibrils is dissolved again. Nephlometry was used to study the rate of fibril formation as a function of pH and temperature values. A conclusion has been drawn that the mature collagne dissolved after incubation with bacterial proteinases is close to the acid-soluble collagen fraction in the ability to produce fibres upon heating.", "contents": "[Fibril formation in solutions of solubilized collagen]. Influence of the preparations of bacterial proteinases, protorisine and prototerrisine, was studied on the stability of the mature collagen of beef skin. The chemical composition of the tissue has been shown to be changed by these enzymes inconsiderably. The tissue treated by orisine and terrisine is completely dissolved in 0.5 M acetic acid (solubilized collagen). When the solutions of such collagen are heated to 37 degrees within the pH range from 4 to 10 at the ionic strength of 0.25 fibrils are formed. Under electron microscope fibres are cross-striated that is typical of native collagen fibres with periodicity of about 640 A. After chilling to 4 degrees, a part of fibrils is dissolved again. Nephlometry was used to study the rate of fibril formation as a function of pH and temperature values. A conclusion has been drawn that the mature collagne dissolved after incubation with bacterial proteinases is close to the acid-soluble collagen fraction in the ability to produce fibres upon heating."}
{"id": "PMID:2340", "title": "PAH clearance, sodium excretion, and PAH extraction ratio in acidotic near-term lambs treated with hypertonic sodium bicarbonate.", "content": "The electrolyte changes and renal hemodynamic adjustment to hypertonic sodium bicarbonate (NaHCO3) correction of a metabolic acidosis were studied in 4 neonatal lambs and in 2 controls. PAH clearance increased from 0.92 to 1.65 ml/min/kg (p less than 0.05),  urine flow from 0.37 to 0.61 ml/min/kg (p less than 0.05), and Na excretion from 8.4 to 23.7 muEq/min/kg (p less than 0.05) during the NaHCO3 infusion. These increases were transient and returned to pre-infusion levels following NaHCO3 infusion. Calculation of Na intake and output revealed a net retention of 5.1 mEq/kg in the study lambs which was reflected in a rise of serum Na and osmolarity (Osm) during the post-NaHCO3 -infusion period. The extraction ratio of sodium p-aminohippurate (EPAH) and its relationship to arterial pH were studied in 4 additional lambs. The EPAH did not change with metabolic acidosis but for unknown reasons, the infusion of NaHCO3 resulted in a temporary depression of EPAH (p less than 0.001).", "contents": "PAH clearance, sodium excretion, and PAH extraction ratio in acidotic near-term lambs treated with hypertonic sodium bicarbonate. The electrolyte changes and renal hemodynamic adjustment to hypertonic sodium bicarbonate (NaHCO3) correction of a metabolic acidosis were studied in 4 neonatal lambs and in 2 controls. PAH clearance increased from 0.92 to 1.65 ml/min/kg (p less than 0.05),  urine flow from 0.37 to 0.61 ml/min/kg (p less than 0.05), and Na excretion from 8.4 to 23.7 muEq/min/kg (p less than 0.05) during the NaHCO3 infusion. These increases were transient and returned to pre-infusion levels following NaHCO3 infusion. Calculation of Na intake and output revealed a net retention of 5.1 mEq/kg in the study lambs which was reflected in a rise of serum Na and osmolarity (Osm) during the post-NaHCO3 -infusion period. The extraction ratio of sodium p-aminohippurate (EPAH) and its relationship to arterial pH were studied in 4 additional lambs. The EPAH did not change with metabolic acidosis but for unknown reasons, the infusion of NaHCO3 resulted in a temporary depression of EPAH (p less than 0.001)."}
{"id": "PMID:2337", "title": "On the proteolytic acitivity of ribosomes.", "content": "The presence of a proteinase on polysomes, isolated from rat liver has been demonstrated. The proteinase was not removed from polysomes upon treatment of the latter with 0,5 M ammonium chloride. The pH optimum of the enzymes is at pH 7,0.", "contents": "On the proteolytic acitivity of ribosomes. The presence of a proteinase on polysomes, isolated from rat liver has been demonstrated. The proteinase was not removed from polysomes upon treatment of the latter with 0,5 M ammonium chloride. The pH optimum of the enzymes is at pH 7,0."}
{"id": "PMID:2343", "title": "[Correction of plasma hemoglobin measurements in calculating a hemolysis index].", "content": "A \"haemolysis index\" may be defined from plasma haemoglobin concentration. This is useful in evaluating the consequences of the artificial kidneys and lungs (pumps and circuitry). Measurements must be taken repeatedly, and corrections made for variations in plasma volume from standard conditions (haematocrit or total haemoglobin) to obtain meaningful comparisons. The \"haemolysis index\" must take into account the number of passages through the circuit.", "contents": "[Correction of plasma hemoglobin measurements in calculating a hemolysis index]. A \"haemolysis index\" may be defined from plasma haemoglobin concentration. This is useful in evaluating the consequences of the artificial kidneys and lungs (pumps and circuitry). Measurements must be taken repeatedly, and corrections made for variations in plasma volume from standard conditions (haematocrit or total haemoglobin) to obtain meaningful comparisons. The \"haemolysis index\" must take into account the number of passages through the circuit."}
{"id": "PMID:2344", "title": "[Study of the osmotic behaviour of human platelets].", "content": "Observation of the behaviour of platelets in hypotonic media affords an approach to the evaluation of their fragility. It should be possible to apply such a test to various fields such as the study of rheological properties of platelets, the investigation of certain pathological cases and eventual alterations during storage. The curve obtained reflects a continuous distribution of platelet osmotic fragility.", "contents": "[Study of the osmotic behaviour of human platelets]. Observation of the behaviour of platelets in hypotonic media affords an approach to the evaluation of their fragility. It should be possible to apply such a test to various fields such as the study of rheological properties of platelets, the investigation of certain pathological cases and eventual alterations during storage. The curve obtained reflects a continuous distribution of platelet osmotic fragility."}
{"id": "PMID:2345", "title": "Oxygen transport by haemoglobin. A comparison of whole blood, washed erythrocytes and haemoglobin solution.", "content": "The properties of haemoglobin oxygen transport were compared under three different conditions: red cell in its natural medium, i.e. plasma (whole blood), washed red cell and haemoglobin A, the former suspended, the latter solved in an iso-osmotic tris buffer. The oxygen haemoglobin affinity (expressed as P50) and the respiratory Bohr effect variations were studied with modified media and unchanged pH and 2,3-diphosphoglycerate (2,3-DPG) concentration. Provided they are refered to intra-erythrocytic pH, none of these values were changed when varying environment. These results suggest that the three major ligands (H+ ions, 2,3-DPG and CO2) interaction with haemoglobin is largely predominant upon other factors which would interfere, and can completely account for oxygen transport by haemoglobin.", "contents": "Oxygen transport by haemoglobin. A comparison of whole blood, washed erythrocytes and haemoglobin solution. The properties of haemoglobin oxygen transport were compared under three different conditions: red cell in its natural medium, i.e. plasma (whole blood), washed red cell and haemoglobin A, the former suspended, the latter solved in an iso-osmotic tris buffer. The oxygen haemoglobin affinity (expressed as P50) and the respiratory Bohr effect variations were studied with modified media and unchanged pH and 2,3-diphosphoglycerate (2,3-DPG) concentration. Provided they are refered to intra-erythrocytic pH, none of these values were changed when varying environment. These results suggest that the three major ligands (H+ ions, 2,3-DPG and CO2) interaction with haemoglobin is largely predominant upon other factors which would interfere, and can completely account for oxygen transport by haemoglobin."}
{"id": "PMID:2346", "title": "Kinetics of the disordered chain-to-beta transformation of poly(L-tyrosine) in aqueous solution.", "content": "The kinetics of the transformation of poly(L-tyrosine) from the disordered chain to the intramolecular beta structure in aqueous solution has been studied. The reaction is induced by an isothermal pH jump and is followed by conventional circular dichroism methods. Upon application of curve-fitting procedures, it is found that the kinetics are poorly represented by a single first-order process, but a two-step sequential first-order equation is adequate. Sharp pH-dependent maxima in the phenomenological rate constants and in the fractional amplitude of the rapid step were found. It is proposed to attribute these phenomena to a transition in initial states which is shown to occur over the same pH range within the domain of the disordered-to-beta transition. No sigmoid transient curves were observed, indicating that no slow nucleation events are discernible in this system. These observations contrast strikingly with the mechanism elaborated for beta formation in (Lys)n [R. Hartman et al., J. Mol. Biol. 90 (1974) 415].", "contents": "Kinetics of the disordered chain-to-beta transformation of poly(L-tyrosine) in aqueous solution. The kinetics of the transformation of poly(L-tyrosine) from the disordered chain to the intramolecular beta structure in aqueous solution has been studied. The reaction is induced by an isothermal pH jump and is followed by conventional circular dichroism methods. Upon application of curve-fitting procedures, it is found that the kinetics are poorly represented by a single first-order process, but a two-step sequential first-order equation is adequate. Sharp pH-dependent maxima in the phenomenological rate constants and in the fractional amplitude of the rapid step were found. It is proposed to attribute these phenomena to a transition in initial states which is shown to occur over the same pH range within the domain of the disordered-to-beta transition. No sigmoid transient curves were observed, indicating that no slow nucleation events are discernible in this system. These observations contrast strikingly with the mechanism elaborated for beta formation in (Lys)n [R. Hartman et al., J. Mol. Biol. 90 (1974) 415]."}
{"id": "PMID:2347", "title": "Thermodynamic investigations of proteins. I. Standard functions for proteins with lysozyme as an example.", "content": "A direct method is proposed for obtaining thermodynamic standard functions for native and denatured proteins using experimental data from scanning calorimetry, isothermal calorimetry and potentiometric titrations. The possibility of this approach is demonstrated on the example of lysozyme in the range of pH 1.5-7.0 and temperature 0-100 degrees C. Tests for the validity of the obtained functions of enthalpy and entropy are presented in the form of cyclic processes using experimental data obtained from thermodynamically different pathways. The Gibbs function is checked by comparison with results of an independent method. The methodic problems in determining and checking standard functions for proteins are discussed in detail.", "contents": "Thermodynamic investigations of proteins. I. Standard functions for proteins with lysozyme as an example. A direct method is proposed for obtaining thermodynamic standard functions for native and denatured proteins using experimental data from scanning calorimetry, isothermal calorimetry and potentiometric titrations. The possibility of this approach is demonstrated on the example of lysozyme in the range of pH 1.5-7.0 and temperature 0-100 degrees C. Tests for the validity of the obtained functions of enthalpy and entropy are presented in the form of cyclic processes using experimental data obtained from thermodynamically different pathways. The Gibbs function is checked by comparison with results of an independent method. The methodic problems in determining and checking standard functions for proteins are discussed in detail."}
{"id": "PMID:2348", "title": "Thermodynamic investigations of proteins. III. Thermodynamic description of lysozyme.", "content": "Standard functions of enthalpy, entropy and the Gibbs energy of native and denatured lysozyme in the range of 0-100 degrees C and pH 1.5-7.0 are represented in three-dimensional projections. The denaturational Gibbs energy change reaches 16 kcal mol-1 at conditions of maximal protein stability (0 degrees C, pH 4.5-7.0) and equals 14.5 kcal mol-1 at 25 degrees C and neutral pH. This result was found to be in agreement with the data reported from guanidine hydrochloride denaturation studies. Partial thermodynamic functions of the conformational and ionizational changes of the protein are obtained from entropy and Gibbs-energy changes in denaturation. The conformational partial entropy and Gibbs-energy change are found to be independent of pH. The pH-dependent partial ionizational entropy and Gibbs-energy changes are induced by normalization of the ionization behaviour of buried groups and cause a decrease of protein stability.", "contents": "Thermodynamic investigations of proteins. III. Thermodynamic description of lysozyme. Standard functions of enthalpy, entropy and the Gibbs energy of native and denatured lysozyme in the range of 0-100 degrees C and pH 1.5-7.0 are represented in three-dimensional projections. The denaturational Gibbs energy change reaches 16 kcal mol-1 at conditions of maximal protein stability (0 degrees C, pH 4.5-7.0) and equals 14.5 kcal mol-1 at 25 degrees C and neutral pH. This result was found to be in agreement with the data reported from guanidine hydrochloride denaturation studies. Partial thermodynamic functions of the conformational and ionizational changes of the protein are obtained from entropy and Gibbs-energy changes in denaturation. The conformational partial entropy and Gibbs-energy change are found to be independent of pH. The pH-dependent partial ionizational entropy and Gibbs-energy changes are induced by normalization of the ionization behaviour of buried groups and cause a decrease of protein stability."}
{"id": "PMID:2349", "title": "The self-association of adenosine-5'-triphosphate studied by circular dichroism at low ionic strengths.", "content": "The self-association of adenosine-5'-triphosphate (ATP) was studied as a function of pH, additional counterions, concentration and temperature. Circular dichroism measurements were employed as a measure of the base-stacking. The self-association of ATP is pH dependent with the protonation of the adenine ring helping stabilize the association. Highly charged counterions alter this aggregation. At pH 2.8 and 20 degrees C, a dimerization constant of 88 M-1 is obtained, while an isodesmic model leads to an equilibrium constant of 158 M-1. With increasing pH, the association constants decrease. At pH 2.8 there is a very strong temperature dependence of the CD amplitude. These results indicate the existence of additional electrostatic stabilization for the stacking of the adenine rings. At acidic pHs, models are proposed to explain this high degree of stability and a calculation of the approximate electrostatic contribution to the aggregation shows it to be of the proper magnitude.", "contents": "The self-association of adenosine-5'-triphosphate studied by circular dichroism at low ionic strengths. The self-association of adenosine-5'-triphosphate (ATP) was studied as a function of pH, additional counterions, concentration and temperature. Circular dichroism measurements were employed as a measure of the base-stacking. The self-association of ATP is pH dependent with the protonation of the adenine ring helping stabilize the association. Highly charged counterions alter this aggregation. At pH 2.8 and 20 degrees C, a dimerization constant of 88 M-1 is obtained, while an isodesmic model leads to an equilibrium constant of 158 M-1. With increasing pH, the association constants decrease. At pH 2.8 there is a very strong temperature dependence of the CD amplitude. These results indicate the existence of additional electrostatic stabilization for the stacking of the adenine rings. At acidic pHs, models are proposed to explain this high degree of stability and a calculation of the approximate electrostatic contribution to the aggregation shows it to be of the proper magnitude."}
{"id": "PMID:2353", "title": "Studies on immobilized trypsin in high concentrations of organic solvents.", "content": "Trypsin was covalently immobilized on porous glass in the presence and absence of a specific substrate and reacted in various organic solvents of different dielectric constants. Optimum solvent concentration, pH profile, Km(app), Vmax(app), productivity versus temperature, activity, and reaction rates were determined. Reaction rates of six lysyl dipeptides were compared. Crystalline trypsin was dansylated for studies by nanosecond fluorescence techniques to determine the effects of introducing high concentrations of organic solvents on the molecule. The results indicated that greater reaction rates were observed with dipeptides having more acidic carboxyl terminal groups. The data also indicated that greater reaction rates were observed in higher concentrations of solvents of lower dielectric constants. Nanosecond fluorescence spectroscopy of trypsin in high concentrations of a low dielectric constant solvent indicated major dehydration even though maximal enzyme activity was achieved under these conditions.", "contents": "Studies on immobilized trypsin in high concentrations of organic solvents. Trypsin was covalently immobilized on porous glass in the presence and absence of a specific substrate and reacted in various organic solvents of different dielectric constants. Optimum solvent concentration, pH profile, Km(app), Vmax(app), productivity versus temperature, activity, and reaction rates were determined. Reaction rates of six lysyl dipeptides were compared. Crystalline trypsin was dansylated for studies by nanosecond fluorescence techniques to determine the effects of introducing high concentrations of organic solvents on the molecule. The results indicated that greater reaction rates were observed with dipeptides having more acidic carboxyl terminal groups. The data also indicated that greater reaction rates were observed in higher concentrations of solvents of lower dielectric constants. Nanosecond fluorescence spectroscopy of trypsin in high concentrations of a low dielectric constant solvent indicated major dehydration even though maximal enzyme activity was achieved under these conditions."}
{"id": "PMID:2354", "title": "Enzyme immobilization on fibrin.", "content": "The following conclusions can be drawn concerning the utilization of fibrin to immobilized enzyme systems. Fibrin can be used both as a powder or membrane, to covalently immobilize trypsin with retention of activity. Carbon-14 labeled trypsin can be used to estimate the amount of immobilized enzyme on a proteinaceous support. Significant amounts of noncovalently coupled (adsorbed) enzyme are present on the surface of the support. Esterase activity of the immobilized labeled trypsin was inversely proportional to the amount of attached enzyme. Optimum TAME hydrolysis occurred at pH 8-8.4. The storage stability of trypsin was enhanced. Inhibition of trypsin esterase activity occurred at substrate concentrations greater than 30mM.", "contents": "Enzyme immobilization on fibrin. The following conclusions can be drawn concerning the utilization of fibrin to immobilized enzyme systems. Fibrin can be used both as a powder or membrane, to covalently immobilize trypsin with retention of activity. Carbon-14 labeled trypsin can be used to estimate the amount of immobilized enzyme on a proteinaceous support. Significant amounts of noncovalently coupled (adsorbed) enzyme are present on the surface of the support. Esterase activity of the immobilized labeled trypsin was inversely proportional to the amount of attached enzyme. Optimum TAME hydrolysis occurred at pH 8-8.4. The storage stability of trypsin was enhanced. Inhibition of trypsin esterase activity occurred at substrate concentrations greater than 30mM."}
{"id": "PMID:2356", "title": "[Neuro-muscular synapse ultrastructure in the Lambert-Eaton myasthenic syndrome].", "content": "A study was made of the ultrastructure of the neuro-muscular synapses in the patients with the myasthenic Lambert-Eaton syndrome. Most of the synapses displayed an increased content of synaptic vesicles in the axon terminals, and the anastomosing synaptic folds were increased in number and depth. Local destructive changes were found in the terminals of some synapses. The data obtained confirmed the fact that this syndrome was underlied by disorder of the transmitter release from the presynaptic structures.", "contents": "[Neuro-muscular synapse ultrastructure in the Lambert-Eaton myasthenic syndrome]. A study was made of the ultrastructure of the neuro-muscular synapses in the patients with the myasthenic Lambert-Eaton syndrome. Most of the synapses displayed an increased content of synaptic vesicles in the axon terminals, and the anastomosing synaptic folds were increased in number and depth. Local destructive changes were found in the terminals of some synapses. The data obtained confirmed the fact that this syndrome was underlied by disorder of the transmitter release from the presynaptic structures."}
{"id": "PMID:2358", "title": "Prostaglandins in pyometrial fluid from the cow, bitch and ferret.", "content": "1 Pyometra is a disorder of the uterus usually associated with bacterial infection plus obstruction. 2 Large quantities of fluid often collect in the uterus during this condition. 3 Pyometrial fluid obtained from three species was found to contain prostaglandin F2alpha, usually in large quantities. 4 Prostaglandin E2 was present in smaller quantities in five of the six samples. 5 These findings are discussed in relation to the known occurrence of prostaglandins in inflammatory fluid, and to the problem of infertility.", "contents": "Prostaglandins in pyometrial fluid from the cow, bitch and ferret. 1 Pyometra is a disorder of the uterus usually associated with bacterial infection plus obstruction. 2 Large quantities of fluid often collect in the uterus during this condition. 3 Pyometrial fluid obtained from three species was found to contain prostaglandin F2alpha, usually in large quantities. 4 Prostaglandin E2 was present in smaller quantities in five of the six samples. 5 These findings are discussed in relation to the known occurrence of prostaglandins in inflammatory fluid, and to the problem of infertility."}
{"id": "PMID:2359", "title": "Assessment in the guinea-pig ileum and mouse vas deferens of benzomorphans which have strong antinociceptive activity but do not substitute for morphine in the dependent monkey.", "content": "1 Four benzomorphans which have potent antinociceptive activity in the hot-plate and writhing tests in the mouse but do not suppress or precipitate withdrawal symptoms in the morphine-dependent monkey, have been examined for their pharmacological actions in the guinea-pig ileum and mouse vas deferens. 2 In the guinea-pig ileum their agonist potencies are 1.5 to 400 times greater than that of normorphine of morphine whereas in the mouse vas deferens their potencies relative to morphine are 0.3 to 100. They exhibit no antagonist activity in either preparation. Benzomorphans which substitute for morphine in the morphine-dependent monkey do not show such differences between their relative potencies in the guinea-pig ileum and mouse vas diferens. 3 The relative potencies of the four benzomorphans to inhibit stereospecific [3H]-dihydromorphine binding by membrane fragments from rat brain, are more closely related to their relative agonist potencies in the mouse vas deferens than to those found in the guinea-pig ileum. 4 In order to antagonize the agonist actions of these benzomorphans, naloxone is required in concentrations which are 3 to 7 times higher than those needed for the antagonism of normorphine or morphine or of benzomorphans which suppress abstinence in morphine-dependent monkeys. 5 It may be possible to use the three assays, namely, ratio of relative agonist potency in mouse vas deferens to that in guinea-pig ileum, ratio of relative agonist potency to relative affinity to opiate receptors and the concentration of nalozone required for antagonism, for the prediction of the potential of new compounds to produce physical dependence.", "contents": "Assessment in the guinea-pig ileum and mouse vas deferens of benzomorphans which have strong antinociceptive activity but do not substitute for morphine in the dependent monkey. 1 Four benzomorphans which have potent antinociceptive activity in the hot-plate and writhing tests in the mouse but do not suppress or precipitate withdrawal symptoms in the morphine-dependent monkey, have been examined for their pharmacological actions in the guinea-pig ileum and mouse vas deferens. 2 In the guinea-pig ileum their agonist potencies are 1.5 to 400 times greater than that of normorphine of morphine whereas in the mouse vas deferens their potencies relative to morphine are 0.3 to 100. They exhibit no antagonist activity in either preparation. Benzomorphans which substitute for morphine in the morphine-dependent monkey do not show such differences between their relative potencies in the guinea-pig ileum and mouse vas diferens. 3 The relative potencies of the four benzomorphans to inhibit stereospecific [3H]-dihydromorphine binding by membrane fragments from rat brain, are more closely related to their relative agonist potencies in the mouse vas deferens than to those found in the guinea-pig ileum. 4 In order to antagonize the agonist actions of these benzomorphans, naloxone is required in concentrations which are 3 to 7 times higher than those needed for the antagonism of normorphine or morphine or of benzomorphans which suppress abstinence in morphine-dependent monkeys. 5 It may be possible to use the three assays, namely, ratio of relative agonist potency in mouse vas deferens to that in guinea-pig ileum, ratio of relative agonist potency to relative affinity to opiate receptors and the concentration of nalozone required for antagonism, for the prediction of the potential of new compounds to produce physical dependence."}
{"id": "PMID:2360", "title": "The actions of flupenthixol upon 5-hydroxytryptamine-induced aggregation and the uptake of 5-hydroxytryptamine and dopamine by human blood platelets.", "content": "The effects of the alpha- and beta-isomers of flupenthixol on 5-hydroxytryptamine (5-HT)-induced platelet aggregation and on 5-HT and dopamine uptake were investigated. Alpha-Flupenthixol was 185 times more potent than the beta-isomer as an inhibitor of platelet  aggregation. In contrast both isomers were equipotent as inhibitors of uptake of 5-HT and dopamine. The data suggest that 5-HT-induced aggregation and uptake are separate processes.", "contents": "The actions of flupenthixol upon 5-hydroxytryptamine-induced aggregation and the uptake of 5-hydroxytryptamine and dopamine by human blood platelets. The effects of the alpha- and beta-isomers of flupenthixol on 5-hydroxytryptamine (5-HT)-induced platelet aggregation and on 5-HT and dopamine uptake were investigated. Alpha-Flupenthixol was 185 times more potent than the beta-isomer as an inhibitor of platelet  aggregation. In contrast both isomers were equipotent as inhibitors of uptake of 5-HT and dopamine. The data suggest that 5-HT-induced aggregation and uptake are separate processes."}
{"id": "PMID:2357", "title": "Evolution of functional respiratory disorders in different types of pneumoconiosis.", "content": "Three homogeneous groups of patients with silicosis, coal workers' pneumoconiosis and arc welders' pneumoconiosis had been reexamined after an interval of six years. The same examinations were repeated on each occasion with the purpose of evaluating the evolution of radiographic and functional changes. The clinical course, roentgenographic findings and results of function tests differed in the three groups. In silicosis and coal workers' pneumoconiosis the roentgenographic changes showed distinct progression. This progression was less evident in coal workers' pneumoconiosis, but deterioration of pulmonary function was more pronounced than in silicosis, apparently due to emphysema. In pneumoconiosis of welders roentgenographic changes showed a clear tendency to regression and respiratory function was not impaired.", "contents": "Evolution of functional respiratory disorders in different types of pneumoconiosis. Three homogeneous groups of patients with silicosis, coal workers' pneumoconiosis and arc welders' pneumoconiosis had been reexamined after an interval of six years. The same examinations were repeated on each occasion with the purpose of evaluating the evolution of radiographic and functional changes. The clinical course, roentgenographic findings and results of function tests differed in the three groups. In silicosis and coal workers' pneumoconiosis the roentgenographic changes showed distinct progression. This progression was less evident in coal workers' pneumoconiosis, but deterioration of pulmonary function was more pronounced than in silicosis, apparently due to emphysema. In pneumoconiosis of welders roentgenographic changes showed a clear tendency to regression and respiratory function was not impaired."}
{"id": "PMID:2367", "title": "Developmental variations of tyrosine hydroxylase and acetylcholinesterase in embryonic and post-hatching chicken sympathetic ganglia.", "content": "The developmental variations of tyrosine hydroxylase (TH) and of acetylcholinesterase (AChE) were studied in embryonic and post-hatching chicken sympathetic ganglia. Different levels of TH activity were found in two different flocks of White Leghorn chicken, which are probably dependent on genetic differences. These enzymatic differences, however, do not become apparent before hatching and may indicate a combined effect of genetic variation and functional demands. During the period of incubation, TH activity is characterized by a pronounced and steady increase from the twelfth day of incubation up to day 2 after hatching. This corresponds to a period of intense maturation of the sympathetic neuron. In the period following hatching, the 'fourth day fall phenomenon' previously described by us for DOPA decarboxylase (DDC), dopamine-beta-hydroxylase (DBH), and monoamine oxidase (MAO) is not seen in the TH curve. Instead, TH activity tends to remain constant between days 2 and 14 after hatching (ah). Both ganglionic protein and weight remain constant in this period, indicating a phase of general pause in protein synthesis. AChE activity increases steadily from the eighth until the twenty-first day of incubation. A sudden and significant drop in AChE activity was found at day 2 ah followed by a period of rapid increase at day 3 ah and a levelling of activity up to day 30 ah. Comparing the present variations to those observed in our previous studies on DBH, a temporal relationship between TH and DBH activity is observed during the phases of synaptogenesis and maturation but not during the phase of intense functional activity. Our results strongly suggest that before hatching in chick embryo sympathetic ganglia, the cholinergic presynaptic terminals play a role in regulating the development of the adrenergic neurons. In the period following hatching, however, the DBH and TH levels in cell bodies seem to be principally regulated by the functional activity. This results in depletion of DBH, but not TH, through liberation along with the neurotransmitter at the periphery. Depletion of DBH at the terminals may result in increased transport and thereby depletion in the cell body. This mechanism is probably responsible for the difference in the profiles of activity of DBH and TH in the cell bodies observed in the first week after hatching.", "contents": "Developmental variations of tyrosine hydroxylase and acetylcholinesterase in embryonic and post-hatching chicken sympathetic ganglia. The developmental variations of tyrosine hydroxylase (TH) and of acetylcholinesterase (AChE) were studied in embryonic and post-hatching chicken sympathetic ganglia. Different levels of TH activity were found in two different flocks of White Leghorn chicken, which are probably dependent on genetic differences. These enzymatic differences, however, do not become apparent before hatching and may indicate a combined effect of genetic variation and functional demands. During the period of incubation, TH activity is characterized by a pronounced and steady increase from the twelfth day of incubation up to day 2 after hatching. This corresponds to a period of intense maturation of the sympathetic neuron. In the period following hatching, the 'fourth day fall phenomenon' previously described by us for DOPA decarboxylase (DDC), dopamine-beta-hydroxylase (DBH), and monoamine oxidase (MAO) is not seen in the TH curve. Instead, TH activity tends to remain constant between days 2 and 14 after hatching (ah). Both ganglionic protein and weight remain constant in this period, indicating a phase of general pause in protein synthesis. AChE activity increases steadily from the eighth until the twenty-first day of incubation. A sudden and significant drop in AChE activity was found at day 2 ah followed by a period of rapid increase at day 3 ah and a levelling of activity up to day 30 ah. Comparing the present variations to those observed in our previous studies on DBH, a temporal relationship between TH and DBH activity is observed during the phases of synaptogenesis and maturation but not during the phase of intense functional activity. Our results strongly suggest that before hatching in chick embryo sympathetic ganglia, the cholinergic presynaptic terminals play a role in regulating the development of the adrenergic neurons. In the period following hatching, however, the DBH and TH levels in cell bodies seem to be principally regulated by the functional activity. This results in depletion of DBH, but not TH, through liberation along with the neurotransmitter at the periphery. Depletion of DBH at the terminals may result in increased transport and thereby depletion in the cell body. This mechanism is probably responsible for the difference in the profiles of activity of DBH and TH in the cell bodies observed in the first week after hatching."}
{"id": "PMID:2369", "title": "[Erythrocyte stroma included in polyacrylamide gel. Applications to affinity chromatography].", "content": "Stromata prepared with human or animal red blood cells are suspended in acrylamide solution. Gel as prepared for electrophoresis is dispersed, before use, and can be used in chromatographic columns for the retention of agglutinins. Lectins, e.g., where first absorbed and then eluted with solution of inhibitory sugar or with acid buffer. Some applications are mentioned.", "contents": "[Erythrocyte stroma included in polyacrylamide gel. Applications to affinity chromatography]. Stromata prepared with human or animal red blood cells are suspended in acrylamide solution. Gel as prepared for electrophoresis is dispersed, before use, and can be used in chromatographic columns for the retention of agglutinins. Lectins, e.g., where first absorbed and then eluted with solution of inhibitory sugar or with acid buffer. Some applications are mentioned."}
{"id": "PMID:2370", "title": "[Value of the \"gastric chamber\", new technic performed ex vivo, for the study of the gastric mucosa of the rat].", "content": "The \"gastric chamber\" technique, performed in the anaesthetised rat, enables the study of gastric mucosal fragility induced by doses of phenylbutazone, which do not themselves cause ulceration or exulceration. The perfusion of buffered solution at pH 2-8 into the gastric chamber shows that prior oral administration of phenylbutazone 50 mg/kg increases the fragility of the mucosa. The optimal delay separating this administration from the time of experimentation is 6 hours. The effects seen are essentially vascular disorders.", "contents": "[Value of the \"gastric chamber\", new technic performed ex vivo, for the study of the gastric mucosa of the rat]. The \"gastric chamber\" technique, performed in the anaesthetised rat, enables the study of gastric mucosal fragility induced by doses of phenylbutazone, which do not themselves cause ulceration or exulceration. The perfusion of buffered solution at pH 2-8 into the gastric chamber shows that prior oral administration of phenylbutazone 50 mg/kg increases the fragility of the mucosa. The optimal delay separating this administration from the time of experimentation is 6 hours. The effects seen are essentially vascular disorders."}
{"id": "PMID:2371", "title": "[Dopamine of the caudate nucleus in Perodictious potto, Macaca mulatta and Macaca fascicularis].", "content": "The dopamine, dopac and tyrosinehydroxylase contents of the caudate nucleus in the prosimian Perodicticus potto and in the simii Macaca mulatta and M. fascicularis have been estimated. The results do not support the hypothesis according to which the sluggishness of the potto is somehow related to a low dopamine content of part of the extrapyramidal system as found in the Parkinson-syndrome.", "contents": "[Dopamine of the caudate nucleus in Perodictious potto, Macaca mulatta and Macaca fascicularis]. The dopamine, dopac and tyrosinehydroxylase contents of the caudate nucleus in the prosimian Perodicticus potto and in the simii Macaca mulatta and M. fascicularis have been estimated. The results do not support the hypothesis according to which the sluggishness of the potto is somehow related to a low dopamine content of part of the extrapyramidal system as found in the Parkinson-syndrome."}
{"id": "PMID:2372", "title": "[The effect of activator on the esterase activity of plasmin obtained by streptokinase].", "content": "In the esterasic dosage of plasminogen, the authors aim to determine the optimal ratio between the amount of streptokinase to add and of plasminogen itself. It is essential that the activator formation be reduced, which explains the dissociations obtained with other methods.", "contents": "[The effect of activator on the esterase activity of plasmin obtained by streptokinase]. In the esterasic dosage of plasminogen, the authors aim to determine the optimal ratio between the amount of streptokinase to add and of plasminogen itself. It is essential that the activator formation be reduced, which explains the dissociations obtained with other methods."}
{"id": "PMID:2373", "title": "[Oxidative metabolism of funicular tissue. II. Determination of the activity of certain Krebs cycle enzymes].", "content": "Previous experiments have suggested that a partial metabolic block might restrain the oxidative metabolism of the cord tissue between the decarboxylation of pyruvate and the oxidation of succinate. Some of the dehydrogenases of the Kreb's cycle were assayed on acetone powders prepared from human cords. Isocitrate dehydrogenases (both NAD and NADP-specific) have much lower activities than the alpha-ketoglutarate- and malate dehydrogenases; a partial block might be located at this level. Moreover, the malic enzyme has a rather high activity, and might play a significant role by regenerating NADPH in a tissue where other sources of this coenzyme are practically absent.", "contents": "[Oxidative metabolism of funicular tissue. II. Determination of the activity of certain Krebs cycle enzymes]. Previous experiments have suggested that a partial metabolic block might restrain the oxidative metabolism of the cord tissue between the decarboxylation of pyruvate and the oxidation of succinate. Some of the dehydrogenases of the Kreb's cycle were assayed on acetone powders prepared from human cords. Isocitrate dehydrogenases (both NAD and NADP-specific) have much lower activities than the alpha-ketoglutarate- and malate dehydrogenases; a partial block might be located at this level. Moreover, the malic enzyme has a rather high activity, and might play a significant role by regenerating NADPH in a tissue where other sources of this coenzyme are practically absent."}
{"id": "PMID:2374", "title": "[The effect of amino acids on the excitability of identified autoactive giant neurons of Achatina fulica F\u00e9russac].", "content": "Effects of the following amino acids were examined on the electrical activity of the two giant neurones (PON and TAN) identified in the subesophageal ganglia of Achatina fulica F\u00e9russac : L-Asp, L-Thr, L-Ser, L-Glu, L-Pro, Gly, L-alpha-Ala, beta-Ala, L-cysteine, L-cystine, L-Val, L-Met, L-Ileu, L-Leu, L-Tyr, L-Phe, L-Lys, L-His, L-Arg, L-Cit, L-Try, GABA and GABOB. Among these substances, we observed an inhibitory effect of GABA and GABOB on the TAN excitability. GABA showed stronger effect on the TAN than GABOB. This effect of GABA was due to producing hyperpolarization on the TAN membrane. GABA showed a slight excitatory effect on the PON. The effect of GABOB on the PON was very weak and unstable.", "contents": "[The effect of amino acids on the excitability of identified autoactive giant neurons of Achatina fulica F\u00e9russac]. Effects of the following amino acids were examined on the electrical activity of the two giant neurones (PON and TAN) identified in the subesophageal ganglia of Achatina fulica F\u00e9russac : L-Asp, L-Thr, L-Ser, L-Glu, L-Pro, Gly, L-alpha-Ala, beta-Ala, L-cysteine, L-cystine, L-Val, L-Met, L-Ileu, L-Leu, L-Tyr, L-Phe, L-Lys, L-His, L-Arg, L-Cit, L-Try, GABA and GABOB. Among these substances, we observed an inhibitory effect of GABA and GABOB on the TAN excitability. GABA showed stronger effect on the TAN than GABOB. This effect of GABA was due to producing hyperpolarization on the TAN membrane. GABA showed a slight excitatory effect on the PON. The effect of GABOB on the PON was very weak and unstable."}
{"id": "PMID:2375", "title": "[Rapid production of a biotin deficiency in mice].", "content": "This work describes a rapid method for the production of a biotin-deficiency in mice. Besides classical morphological symptoms, a decrease of activities of some biotin-dependent enzymes was also observed. The biotin-enzymes are not inhibited at the same extent in a same organ and the metabolic changes do not always follow the enzymatic modifications.", "contents": "[Rapid production of a biotin deficiency in mice]. This work describes a rapid method for the production of a biotin-deficiency in mice. Besides classical morphological symptoms, a decrease of activities of some biotin-dependent enzymes was also observed. The biotin-enzymes are not inhibited at the same extent in a same organ and the metabolic changes do not always follow the enzymatic modifications."}
{"id": "PMID:2376", "title": "[Ciguatera: neurophysiologic and histoenzymologic studies of several fractions of ciguatoxic extracts].", "content": "Two fractions of ciguatoxic extracts were isolated by chromatography. The first showed anticholinesterasic properties, while the other acted directly on the muscular fibre. These findings were histoenzymologically confirmed. Controls with non-toxic extracts of fishes from the coral benthos reinforce the theory of the ecological origins of ciguatoxins.", "contents": "[Ciguatera: neurophysiologic and histoenzymologic studies of several fractions of ciguatoxic extracts]. Two fractions of ciguatoxic extracts were isolated by chromatography. The first showed anticholinesterasic properties, while the other acted directly on the muscular fibre. These findings were histoenzymologically confirmed. Controls with non-toxic extracts of fishes from the coral benthos reinforce the theory of the ecological origins of ciguatoxins."}
{"id": "PMID:2377", "title": "Lorazepam as a premedication.", "content": "A double-blind random study compared the effects of lorazepam and pantopon an intra-muscular premedication in healthy women for uterine curettage (D & C). Anxiety, as assessed by a self-rating test by the patient and by a trained observer, showed a significant reduction at one and one-half hours after lorazepam and a smaller reduction after pantopon, which was not significant. Sedation was satisfactory with no significant difference between the two drugs in the change before and after the premedication. Lorazepam showed much more amnesia than pantopon (p less than 0.001). The patients who had lorazepam required higher doses of thiopentone for the operation, and this, in part, led to longer intervals in recovery times after lorazepam. However, it is suggested that lorazepam itself was partly responsible for the longer recovery. Pantopon was followed by more nausea, vomiting and headaches, than lorazepam. The intra-muscular injection of lorazepam hurt more patients than did pantopon, but other local complications were negligible and comparable in both groups. The results of this study show that lorazepam produces better reduction of anxiety and much more amnesia than pantopon, with comparable sedation and much less nausea and vomiting. The only disadvantage of lorazepam is the lack of analgesia and, therefore, the need for more anaesthesia during the operation. The conclusion is that lorazepam is a very satisfactory premedication and warrants more use as such.", "contents": "Lorazepam as a premedication. A double-blind random study compared the effects of lorazepam and pantopon an intra-muscular premedication in healthy women for uterine curettage (D & C). Anxiety, as assessed by a self-rating test by the patient and by a trained observer, showed a significant reduction at one and one-half hours after lorazepam and a smaller reduction after pantopon, which was not significant. Sedation was satisfactory with no significant difference between the two drugs in the change before and after the premedication. Lorazepam showed much more amnesia than pantopon (p less than 0.001). The patients who had lorazepam required higher doses of thiopentone for the operation, and this, in part, led to longer intervals in recovery times after lorazepam. However, it is suggested that lorazepam itself was partly responsible for the longer recovery. Pantopon was followed by more nausea, vomiting and headaches, than lorazepam. The intra-muscular injection of lorazepam hurt more patients than did pantopon, but other local complications were negligible and comparable in both groups. The results of this study show that lorazepam produces better reduction of anxiety and much more amnesia than pantopon, with comparable sedation and much less nausea and vomiting. The only disadvantage of lorazepam is the lack of analgesia and, therefore, the need for more anaesthesia during the operation. The conclusion is that lorazepam is a very satisfactory premedication and warrants more use as such."}
{"id": "PMID:2378", "title": "Studies on fazadinium bromide (ah 8165): a new non-depolarizing neuromuscular blocking agent.", "content": "Intravenous dose-response relationships were used to correlate neuromuscular paralysis with the effects of fazadinium (AH 8165) on autonomic mechanisms in anaesthetized cats and rhesus monkeys and with cardiovascular effects in man. In cats and monkeys neuromuscular paralysis of the twitch responses of the gastrocnemius muscle by fazadinium was accompanied by impairment of the vagally induced bradycardia, but cardiovascular disturbances were small. Blockade of sympathetic mechanisms and hypotension were only evident with supra-maximal doses. In man tachycardia was a common occurrence and in some patients hypertension occurred with doses of the drug needed for complete neuromuscular paralysis. Fazadinium was three to four times more potent in rhesus monkeys than in cats and its course of action was considerably longer. The potency of the drug in man corresponded more closely to that in cats than in rhesus monkeys but its course of action in patients was similar to that in monkeys. In man, dose-response curves were constructed for the contractions of the adductor pollicis muscles elicited by tetanic and single twitch stimuli applied to the corresponding ulnar nerves. The onset of paralysis of the tetanic contractions after the intravenous injection of fazadinium (0.4 mg/kg) occurred within two minutes, but recovery was slow and about 50 minutes were needed for its completion. Depression of the simultaneously recorded twitch responses was less marked, slower in onset and recovery was slightly more rapid. These effects were similar to those obtained with tubocurarine (0.2 mg/kg) but the action of fazadinium was slightly shorter. Tetanic-tension ratios were computed after 30 and 50 per cent recovery from neruomuscular blockade in man. These ratios were lower with fazadinium than with tubocurarine and indicated taht tetanic fade was greater and more persistent after fazadinium than after tubocurarine.", "contents": "Studies on fazadinium bromide (ah 8165): a new non-depolarizing neuromuscular blocking agent. Intravenous dose-response relationships were used to correlate neuromuscular paralysis with the effects of fazadinium (AH 8165) on autonomic mechanisms in anaesthetized cats and rhesus monkeys and with cardiovascular effects in man. In cats and monkeys neuromuscular paralysis of the twitch responses of the gastrocnemius muscle by fazadinium was accompanied by impairment of the vagally induced bradycardia, but cardiovascular disturbances were small. Blockade of sympathetic mechanisms and hypotension were only evident with supra-maximal doses. In man tachycardia was a common occurrence and in some patients hypertension occurred with doses of the drug needed for complete neuromuscular paralysis. Fazadinium was three to four times more potent in rhesus monkeys than in cats and its course of action was considerably longer. The potency of the drug in man corresponded more closely to that in cats than in rhesus monkeys but its course of action in patients was similar to that in monkeys. In man, dose-response curves were constructed for the contractions of the adductor pollicis muscles elicited by tetanic and single twitch stimuli applied to the corresponding ulnar nerves. The onset of paralysis of the tetanic contractions after the intravenous injection of fazadinium (0.4 mg/kg) occurred within two minutes, but recovery was slow and about 50 minutes were needed for its completion. Depression of the simultaneously recorded twitch responses was less marked, slower in onset and recovery was slightly more rapid. These effects were similar to those obtained with tubocurarine (0.2 mg/kg) but the action of fazadinium was slightly shorter. Tetanic-tension ratios were computed after 30 and 50 per cent recovery from neruomuscular blockade in man. These ratios were lower with fazadinium than with tubocurarine and indicated taht tetanic fade was greater and more persistent after fazadinium than after tubocurarine."}
{"id": "PMID:2379", "title": "Biology of large bowel cancer. Present status and research frontiers.", "content": "Man and laboratory rodents exposed to chemical carcinogens both show changes in growth characteristics of colonic epithelial cells during neoplastic transformation. Progressive phases of abnormal cell development appear in colonic epithelial cells which gain an increased ability to proliferate and accumulate in the mucosa. These phases in the expression of neoplastic transformation of colonic cells are best defined in the dominant inherited disease of man as adenomatosis of the colon and rectum. Individuals with inherited adenomatosis and those in lesser risk categories can be classified by cell phenotype based on changes in the proliferation and maturation of colonic and other cells. These classifications are leading to new predictive indices which identify heightened degrees of susceptibility of individuals who are at increased risk for colon cancer, and the stage of development of their disease. The indices also are being used to study the contribution of specific elements in the enviroment that modify or accelerate the progression of disease.", "contents": "Biology of large bowel cancer. Present status and research frontiers. Man and laboratory rodents exposed to chemical carcinogens both show changes in growth characteristics of colonic epithelial cells during neoplastic transformation. Progressive phases of abnormal cell development appear in colonic epithelial cells which gain an increased ability to proliferate and accumulate in the mucosa. These phases in the expression of neoplastic transformation of colonic cells are best defined in the dominant inherited disease of man as adenomatosis of the colon and rectum. Individuals with inherited adenomatosis and those in lesser risk categories can be classified by cell phenotype based on changes in the proliferation and maturation of colonic and other cells. These classifications are leading to new predictive indices which identify heightened degrees of susceptibility of individuals who are at increased risk for colon cancer, and the stage of development of their disease. The indices also are being used to study the contribution of specific elements in the enviroment that modify or accelerate the progression of disease."}
{"id": "PMID:2380", "title": "Laboratory aids to diagnosis--enzymes.", "content": "A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.", "contents": "Laboratory aids to diagnosis--enzymes. A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer."}
{"id": "PMID:2381", "title": "Increase in alkaline phosphatase activity in the liver of mice bearing Ehrlich ascites tumor.", "content": "In mice bearing Ehrilich ascites tumors, alkaline phosphatase activity was increased fivefold in the liver and by 50% in the kidney. In mice bearing solid tumors caused by inoculation of tumor cells into the axillary region, the activity of this enzyme in the liver was increased 11-fold, whereas the activity in the kidney did not change. Alkaline phosphatase activities in the liver and kidney were not altered by administration of adrenal steroids. Adrenalectomy, fasting, and pregnancy did not affect the activity of alkaline phosphatase in the liver and kidney. Treatment with tumor extracts or ascites fluid of normal mice increased liver alkaline phosphatase activity. These findings suggested that the elevation of liver alkaline phosphatase activity was cuased primarily by the tumor itself, and not by hormonal imbalance provoked secondarily by the presence of the tumor.", "contents": "Increase in alkaline phosphatase activity in the liver of mice bearing Ehrlich ascites tumor. In mice bearing Ehrilich ascites tumors, alkaline phosphatase activity was increased fivefold in the liver and by 50% in the kidney. In mice bearing solid tumors caused by inoculation of tumor cells into the axillary region, the activity of this enzyme in the liver was increased 11-fold, whereas the activity in the kidney did not change. Alkaline phosphatase activities in the liver and kidney were not altered by administration of adrenal steroids. Adrenalectomy, fasting, and pregnancy did not affect the activity of alkaline phosphatase in the liver and kidney. Treatment with tumor extracts or ascites fluid of normal mice increased liver alkaline phosphatase activity. These findings suggested that the elevation of liver alkaline phosphatase activity was cuased primarily by the tumor itself, and not by hormonal imbalance provoked secondarily by the presence of the tumor."}
{"id": "PMID:2382", "title": "Monoamine storage sites in the rat superior cervical ganglion following synthesis inhibition.", "content": "Monoamine storage sites in paraganglionic (PG-) cells of the rat superior cervical ganglion were investigated by electron and fluorescence microscopy following treatment with p-chlorophenylalanine (pCPA), disulfiram or guanethidine respectively. Dense core vesicles in PG-cells are significantly decreased (p less than 0.001) in number following pCPA, and in the majority of these cells following disulfiram and guanethidine. However in a minor portion of PG-cells the latter agents cause an increase in number and in size of dense core vesicles, in parallel with structural alterations. In agreement with these electron microscopic findings fluorescence microscopic and cytophotometric evaluations reveal a general decrease in catecholamine content with few cells showing an increase. The findings provide a morphological basis for the assumption, that monoamine storage sites in PG-cells can be decreased by inhibition of monoamine synthesis, following administration of pCPA, disulfiram and guanethidine. However the two types of responses of PG-cells which occur after disulfiram and guanethidine demonstrate a functional heterogeneity of this cell system in the rat superior cervical ganglion which is discussed.", "contents": "Monoamine storage sites in the rat superior cervical ganglion following synthesis inhibition. Monoamine storage sites in paraganglionic (PG-) cells of the rat superior cervical ganglion were investigated by electron and fluorescence microscopy following treatment with p-chlorophenylalanine (pCPA), disulfiram or guanethidine respectively. Dense core vesicles in PG-cells are significantly decreased (p less than 0.001) in number following pCPA, and in the majority of these cells following disulfiram and guanethidine. However in a minor portion of PG-cells the latter agents cause an increase in number and in size of dense core vesicles, in parallel with structural alterations. In agreement with these electron microscopic findings fluorescence microscopic and cytophotometric evaluations reveal a general decrease in catecholamine content with few cells showing an increase. The findings provide a morphological basis for the assumption, that monoamine storage sites in PG-cells can be decreased by inhibition of monoamine synthesis, following administration of pCPA, disulfiram and guanethidine. However the two types of responses of PG-cells which occur after disulfiram and guanethidine demonstrate a functional heterogeneity of this cell system in the rat superior cervical ganglion which is discussed."}
{"id": "PMID:2383", "title": "Ultracytochemistry of the synaptic ribbons in the rat pineal organ.", "content": "The synaptic complexes of the rat pinealocytes are neither cholinergic nor adrenergic. In the synaptic vesicles, a neurotransmitter carrier substance of lipid nature reacting with OsO4-Zn I2 mixture (similar to that present in both cholinergic and adrenergic vesicles) was not found. In addition, there were no indications of glucose-6-phosphatase or thiamine-pyrophosphatase activity in the synaptic vesicles. Thus, it appears that the synaptic vesicles do not originate from the rough or smooth endoplasmic reticulum. The synaptic ribbons do not contain carbohydrates, are of protein nature and possess some chemical resemblance to microtubules and microtubular bouquets. Appropriate ultracytochemical reactions have not shown detectable quantities of sodium and calcium ions in pinealocyte synaptic complexes.", "contents": "Ultracytochemistry of the synaptic ribbons in the rat pineal organ. The synaptic complexes of the rat pinealocytes are neither cholinergic nor adrenergic. In the synaptic vesicles, a neurotransmitter carrier substance of lipid nature reacting with OsO4-Zn I2 mixture (similar to that present in both cholinergic and adrenergic vesicles) was not found. In addition, there were no indications of glucose-6-phosphatase or thiamine-pyrophosphatase activity in the synaptic vesicles. Thus, it appears that the synaptic vesicles do not originate from the rough or smooth endoplasmic reticulum. The synaptic ribbons do not contain carbohydrates, are of protein nature and possess some chemical resemblance to microtubules and microtubular bouquets. Appropriate ultracytochemical reactions have not shown detectable quantities of sodium and calcium ions in pinealocyte synaptic complexes."}
{"id": "PMID:2387", "title": "Afferent neural pathway in the regulation of cardiopulmonary responses to tissue hypermetabolism.", "content": "We studied the role of neural transmission from hypermetabolic peripheral tissues in the regulation of cardiac output and pulmonary ventilation in chloralose-anesthetized dogs. Cross-circulation techniques with femoral-femoral or femoral-aortic anastomoses were used to produce a vascularly isolated, but normally innervated, hindlimb or lower half-body, 2,4-Dinitrophenol (DNP) was infused into the arterial side of the perfusion circuit to triple oxygen consumption and to increase lactate production by the cross-perfused area. After infusion of DNP, cardiac output and mean systemic arterial blood pressure increased, but neither heart rate nor pulmonary artery wedge pressure changed significantly. Pulmonary minute ventilation and arterial pH also increased, while arterial PCO2 fell. These changes were abolished when the nerve connections between the perfused limb and its parent body were severed. Normal saline, when administered in a similar manner, did not increase either ventilation or cardiac output, and simple denervation without previous infusions of DNP also had no effect. These results indicate that there are receptors sensitive to metabolic changes in the tissue, and that neural transmission is an important afferent link in regulating the cardiopulmonary responses to increased tissue metabolism.", "contents": "Afferent neural pathway in the regulation of cardiopulmonary responses to tissue hypermetabolism. We studied the role of neural transmission from hypermetabolic peripheral tissues in the regulation of cardiac output and pulmonary ventilation in chloralose-anesthetized dogs. Cross-circulation techniques with femoral-femoral or femoral-aortic anastomoses were used to produce a vascularly isolated, but normally innervated, hindlimb or lower half-body, 2,4-Dinitrophenol (DNP) was infused into the arterial side of the perfusion circuit to triple oxygen consumption and to increase lactate production by the cross-perfused area. After infusion of DNP, cardiac output and mean systemic arterial blood pressure increased, but neither heart rate nor pulmonary artery wedge pressure changed significantly. Pulmonary minute ventilation and arterial pH also increased, while arterial PCO2 fell. These changes were abolished when the nerve connections between the perfused limb and its parent body were severed. Normal saline, when administered in a similar manner, did not increase either ventilation or cardiac output, and simple denervation without previous infusions of DNP also had no effect. These results indicate that there are receptors sensitive to metabolic changes in the tissue, and that neural transmission is an important afferent link in regulating the cardiopulmonary responses to increased tissue metabolism."}
{"id": "PMID:2388", "title": "Determination of the molar absorptivity of NADH.", "content": "The molar absorptivity of NADH at 340 nm has been determined by an indirect procedure in which high-purity glucose is phosphorylated by ATP in the presence of hexokinase, coupled to oxidation of the glucose-6-phosphate by NAD+ in the presence of glucose-6-phosphate dehydrogenase. The average value from 85 independent determinations is 6317 liter mol-1 cm-1 at 25 degrees C and pH 7.8. The overall uncertainty is -4.0 to +5.5 ppt (6292 to 6352 liter mol-1 cm-1), based on a standard error of the mean of 0.48 ppt and an estimate of systematic error of -2.6 to +4.1 ppt. Effects of pH, buffer, and temperature on the molar absorptivity are also reported.", "contents": "Determination of the molar absorptivity of NADH. The molar absorptivity of NADH at 340 nm has been determined by an indirect procedure in which high-purity glucose is phosphorylated by ATP in the presence of hexokinase, coupled to oxidation of the glucose-6-phosphate by NAD+ in the presence of glucose-6-phosphate dehydrogenase. The average value from 85 independent determinations is 6317 liter mol-1 cm-1 at 25 degrees C and pH 7.8. The overall uncertainty is -4.0 to +5.5 ppt (6292 to 6352 liter mol-1 cm-1), based on a standard error of the mean of 0.48 ppt and an estimate of systematic error of -2.6 to +4.1 ppt. Effects of pH, buffer, and temperature on the molar absorptivity are also reported."}
{"id": "PMID:2389", "title": "Molar absorptivities of beta-NADH and beta-NADPH.", "content": "Re-investigating the accuracy of the commonly used values for molar absorptivities (epsilon) of beta-NADH and beta-NADPH at Hg 334, Hg 365, or 340 nm, we obtained the following results: The maximum of absorbance of NADH is shifted from about 340 nm at 0 degrees C to about 338.5 nm at 38 degrees C; the corresponding maxima of NADPH are located at about 0.5-nm longer wavelengths. In addition, the absorption curves of both coenzymes broaden with increasing temperature. For these reasons, the epsilon-values of NADH and NADPH are generally different from each other, and are temperature-dependent. Only at 334 nm are they almost identical and nearly independent of temperature. Therefore this wavelength is recommended for precise measurements. The epsilon-values of these coenzymes are influenced by ionic strength and pH. To determine the absolute values of the molar absorptivities, we performed the glutamate dehydrogenase or lactate dehydrogenase assay with carefully purified 2-oxoglutaric acid or pyruvic acid in the presence of excess coenzyme. The purity of the substrates was checked through differential scanning calorimetry, moisture analysis, gas-liquid chromatography, gas chromatography in combination with mass spectrometry, and nuclear magnetic resonance spectroscopy. The epsilon-values observed under the various conditions are about 1-7% higher than those currently used.", "contents": "Molar absorptivities of beta-NADH and beta-NADPH. Re-investigating the accuracy of the commonly used values for molar absorptivities (epsilon) of beta-NADH and beta-NADPH at Hg 334, Hg 365, or 340 nm, we obtained the following results: The maximum of absorbance of NADH is shifted from about 340 nm at 0 degrees C to about 338.5 nm at 38 degrees C; the corresponding maxima of NADPH are located at about 0.5-nm longer wavelengths. In addition, the absorption curves of both coenzymes broaden with increasing temperature. For these reasons, the epsilon-values of NADH and NADPH are generally different from each other, and are temperature-dependent. Only at 334 nm are they almost identical and nearly independent of temperature. Therefore this wavelength is recommended for precise measurements. The epsilon-values of these coenzymes are influenced by ionic strength and pH. To determine the absolute values of the molar absorptivities, we performed the glutamate dehydrogenase or lactate dehydrogenase assay with carefully purified 2-oxoglutaric acid or pyruvic acid in the presence of excess coenzyme. The purity of the substrates was checked through differential scanning calorimetry, moisture analysis, gas-liquid chromatography, gas chromatography in combination with mass spectrometry, and nuclear magnetic resonance spectroscopy. The epsilon-values observed under the various conditions are about 1-7% higher than those currently used."}
{"id": "PMID:2390", "title": "Analysis for indole compounds in urine by high-performance liquid chromatography with fluorometric detection.", "content": "We describe a chromatographic system involving a high-performance chemically-bonded reverse-phase column and fluorescence detection for measurement of indoles in urine. We controlled retention and selectivity by optimizing the methanol content and pH of the mobile phase. Six reference indoles were separated in less than 20 min; three 5-hydroxyindoles were eluted in less than 7 min. About 5-15 ng of aqueous solutions of these compounds can be detected. The combination of selectivity (from use of the chromatographic column) and fluorescence detection permitted analysis for five of the six indoles after a single urine-deproteinization step.", "contents": "Analysis for indole compounds in urine by high-performance liquid chromatography with fluorometric detection. We describe a chromatographic system involving a high-performance chemically-bonded reverse-phase column and fluorescence detection for measurement of indoles in urine. We controlled retention and selectivity by optimizing the methanol content and pH of the mobile phase. Six reference indoles were separated in less than 20 min; three 5-hydroxyindoles were eluted in less than 7 min. About 5-15 ng of aqueous solutions of these compounds can be detected. The combination of selectivity (from use of the chromatographic column) and fluorescence detection permitted analysis for five of the six indoles after a single urine-deproteinization step."}
{"id": "PMID:2391", "title": "Effect of halothane anesthesia on muscle, liver, thyroid, and adrenal-function tests in man.", "content": "Seven healthy men volunteers received 6.6 +/- 1.3 (SD) percent-hours of halothane oxygen anesthesia without surgery. Serum bilirubin, alanine aminotransferase, and aspartate aminotransferase significantly increased after anesthesia, which may indicate subclinical liver-cell damage. Creatine kinase of skeletal muscle origin increased above 90 U/liter in six subjects, indicating subclinical muscle-cell damage. Cortisol, triiodothyronine uptake, thyroxine, and free thyroxine index increased significantly immediately after anesthesia. Serum bromide concentrations had increased by fivefold on the second day after anesthesia, and on the ninth day was still elevated fourfold. Oral temperatures increased 0.7 degrees C 6 h post-anesthesia, possibly because of increased thyroxine activity. Lactate dehydrogenase, hydroxybutyrate dehydrogenase and gamma-glutamyltransferase activities did not change significantly. No drugs administered during the course of this study chemically interfered with any of the test methods used.", "contents": "Effect of halothane anesthesia on muscle, liver, thyroid, and adrenal-function tests in man. Seven healthy men volunteers received 6.6 +/- 1.3 (SD) percent-hours of halothane oxygen anesthesia without surgery. Serum bilirubin, alanine aminotransferase, and aspartate aminotransferase significantly increased after anesthesia, which may indicate subclinical liver-cell damage. Creatine kinase of skeletal muscle origin increased above 90 U/liter in six subjects, indicating subclinical muscle-cell damage. Cortisol, triiodothyronine uptake, thyroxine, and free thyroxine index increased significantly immediately after anesthesia. Serum bromide concentrations had increased by fivefold on the second day after anesthesia, and on the ninth day was still elevated fourfold. Oral temperatures increased 0.7 degrees C 6 h post-anesthesia, possibly because of increased thyroxine activity. Lactate dehydrogenase, hydroxybutyrate dehydrogenase and gamma-glutamyltransferase activities did not change significantly. No drugs administered during the course of this study chemically interfered with any of the test methods used."}
{"id": "PMID:2392", "title": "Improved assay for urinary 17-hydroxycorticosteroids.", "content": "We describe a simple, rapid, reliable method for determining urinary 17-hydroxycorticosteroids. A neutral resin (Amberlite XAD-2), which is a non-ionic cross-linked polystyrene, is used to extract and concentrate the steroids, which are then quantitatively determined with the Porter-Silber reaction. Use of the resin eliminates the need for enzymatic hydrolysis and n-butanol extractions, thereby decreasing analysis time considerably; results can be obtained within 3 h of receipt of specimens. Most of the nonsteroidal Porter-Silber chromogens are removed, resulting in a method that is highly specific and sensitive, even at low concentrations (0.6 mg/liter), and so more accurate and reproducible than currently used methods.", "contents": "Improved assay for urinary 17-hydroxycorticosteroids. We describe a simple, rapid, reliable method for determining urinary 17-hydroxycorticosteroids. A neutral resin (Amberlite XAD-2), which is a non-ionic cross-linked polystyrene, is used to extract and concentrate the steroids, which are then quantitatively determined with the Porter-Silber reaction. Use of the resin eliminates the need for enzymatic hydrolysis and n-butanol extractions, thereby decreasing analysis time considerably; results can be obtained within 3 h of receipt of specimens. Most of the nonsteroidal Porter-Silber chromogens are removed, resulting in a method that is highly specific and sensitive, even at low concentrations (0.6 mg/liter), and so more accurate and reproducible than currently used methods."}
{"id": "PMID:2393", "title": "Radioimmunoassay of plasma renin activity.", "content": "We describe a sensitive, simplified radioimmunoassay method for determination of plasma renin activity. Plasma was acidified to the optimal pH (6.0) of angiotensin l generation with the least possible dilution, by using a single addition of hydrochloric acid and the enzyme inhibitor hydroxyquinoline. Recovery of unlabeled angiotensin l added to plasma was 92-97%; that of monoiodinated angiotensin l exceeded 90%, indicating satisfactory protection from proteolytic enzymes. Plasma constituents interfered little with the radioimmunoassay. Bland values for plasma kept at 0 degrees C were 10.7 +/- 2.3 (mean +/- SD) percent of the activity values for samples kept at +37 degrees C (n equals 63). In the routine setting, 6.25 pg of angiotensin l or 10(-6) Goldblatt units of Standard Human Renin was detected. We report results of plasma renin activity measurements and a comparison with seven renin kits, and with bioassay for plasma renin activity.", "contents": "Radioimmunoassay of plasma renin activity. We describe a sensitive, simplified radioimmunoassay method for determination of plasma renin activity. Plasma was acidified to the optimal pH (6.0) of angiotensin l generation with the least possible dilution, by using a single addition of hydrochloric acid and the enzyme inhibitor hydroxyquinoline. Recovery of unlabeled angiotensin l added to plasma was 92-97%; that of monoiodinated angiotensin l exceeded 90%, indicating satisfactory protection from proteolytic enzymes. Plasma constituents interfered little with the radioimmunoassay. Bland values for plasma kept at 0 degrees C were 10.7 +/- 2.3 (mean +/- SD) percent of the activity values for samples kept at +37 degrees C (n equals 63). In the routine setting, 6.25 pg of angiotensin l or 10(-6) Goldblatt units of Standard Human Renin was detected. We report results of plasma renin activity measurements and a comparison with seven renin kits, and with bioassay for plasma renin activity."}
{"id": "PMID:2394", "title": "P-Hydroxybenzoic acid hydrazide procedure for serum glucose adapted to the Technicon \"SMA 12/60,\" and compared with other glucose methods.", "content": "We adapted the p-hydroxybenzoic acid hydrazide procedure for serum glucose for use with the Technicon SMA 12/60 AutoAnalyzer. Like the o-toluidine method, this method is based on a general carbohydrate reaction except that it occurs in a mildly alkaline medium and the intense yellow color formed is measured at 400 nm. Advantages of this reagent over o-toluidine include lower cost, less toxicity, and higher purity. Aside from those carbohydrates that are present in serum in insignificant quantities, there are no interferences from various physiological compounds or drugs (hypoglycemic agents) found either in normal persons or diabetics. Within-run and day-to-day values had coefficients of variation of 1.39% and 3.44%, respectively; recoveries ranged from 100 to 102% (mean, 101%). Comparative data showed excellent agreement with the hexokinase (r equals 0.998; y equals 0.950x + 5.91) and glucose oxidase (r equals 0.996; y equals 0.986x + 5.34) enzymatic (\"true\") glucose methods, and with the o-toluidine procedure (r equals 0.998; y equals 0.979x + 3.14).", "contents": "P-Hydroxybenzoic acid hydrazide procedure for serum glucose adapted to the Technicon \"SMA 12/60,\" and compared with other glucose methods. We adapted the p-hydroxybenzoic acid hydrazide procedure for serum glucose for use with the Technicon SMA 12/60 AutoAnalyzer. Like the o-toluidine method, this method is based on a general carbohydrate reaction except that it occurs in a mildly alkaline medium and the intense yellow color formed is measured at 400 nm. Advantages of this reagent over o-toluidine include lower cost, less toxicity, and higher purity. Aside from those carbohydrates that are present in serum in insignificant quantities, there are no interferences from various physiological compounds or drugs (hypoglycemic agents) found either in normal persons or diabetics. Within-run and day-to-day values had coefficients of variation of 1.39% and 3.44%, respectively; recoveries ranged from 100 to 102% (mean, 101%). Comparative data showed excellent agreement with the hexokinase (r equals 0.998; y equals 0.950x + 5.91) and glucose oxidase (r equals 0.996; y equals 0.986x + 5.34) enzymatic (\"true\") glucose methods, and with the o-toluidine procedure (r equals 0.998; y equals 0.979x + 3.14)."}
{"id": "PMID:2395", "title": "Lipoamide dehydrogenase in serum: a preliminary report.", "content": "Lipoamide dehydrogenase was identified in serum and the optimal conditions for its assay at 30 degrees C were defined. The pH optimum in tris(hydroxymethyl)aminomethane buffer is 7.8, and activity is inhibited if buffer concentration exceeds 100 mmol/liter. Saturating concentrations of the substrates NAD+ and lipoamide are 3 mmol/liter and 5 mmol/liter, respectively. Activity is decreased eightfold when lipoic acid is substituted for lipoamide. Activity is linearly related to enzyme concentration up to limiting absorbance change of 0.300 at 340 nm, and both within-day and day-to-day precision are satisfactory. Data suggest a normal range (2 SD) of 3-19 kU/liter. The highest value measured in serum was 473 kU/liter. A correlation with direct bilirubin concentrations (r equals 0.435, P less than 0.01) was found.", "contents": "Lipoamide dehydrogenase in serum: a preliminary report. Lipoamide dehydrogenase was identified in serum and the optimal conditions for its assay at 30 degrees C were defined. The pH optimum in tris(hydroxymethyl)aminomethane buffer is 7.8, and activity is inhibited if buffer concentration exceeds 100 mmol/liter. Saturating concentrations of the substrates NAD+ and lipoamide are 3 mmol/liter and 5 mmol/liter, respectively. Activity is decreased eightfold when lipoic acid is substituted for lipoamide. Activity is linearly related to enzyme concentration up to limiting absorbance change of 0.300 at 340 nm, and both within-day and day-to-day precision are satisfactory. Data suggest a normal range (2 SD) of 3-19 kU/liter. The highest value measured in serum was 473 kU/liter. A correlation with direct bilirubin concentrations (r equals 0.435, P less than 0.01) was found."}
{"id": "PMID:2396", "title": "Direct radioimmunoassay of plasma cortisol.", "content": "The simplification of the measurement of circulating cortisol by direct radioimmunoassay of plasma samples sets the problem of inhibiting the carrier proteins competing with antibodies. This was accomplished by exploiting the much higher effectiveness of pH and temperature variations on steroid binding to carrier proteins than to antibody sites. A solid-phase system was set up, using antisera to cortisol-21-BSA conjucates coupled to CNBr-activated cellulose. The standardized procedure consisted of an incubation at pH 3.5 and room temperature, directly assaying 10 mul of plasma. A methodological and clinical validation of the measurement was carried out through a series of tests aimed at assessing the reliability of results (assay of steroid-deprived plasma, recovery test and serial dilution of samples, comparison between different antisera and with different methods including extraction, responsiveness to well-established physiological situations). The results obtained are reported and the validity of the method discussed in terms of more general applicability to steroid assay.", "contents": "Direct radioimmunoassay of plasma cortisol. The simplification of the measurement of circulating cortisol by direct radioimmunoassay of plasma samples sets the problem of inhibiting the carrier proteins competing with antibodies. This was accomplished by exploiting the much higher effectiveness of pH and temperature variations on steroid binding to carrier proteins than to antibody sites. A solid-phase system was set up, using antisera to cortisol-21-BSA conjucates coupled to CNBr-activated cellulose. The standardized procedure consisted of an incubation at pH 3.5 and room temperature, directly assaying 10 mul of plasma. A methodological and clinical validation of the measurement was carried out through a series of tests aimed at assessing the reliability of results (assay of steroid-deprived plasma, recovery test and serial dilution of samples, comparison between different antisera and with different methods including extraction, responsiveness to well-established physiological situations). The results obtained are reported and the validity of the method discussed in terms of more general applicability to steroid assay."}
{"id": "PMID:2397", "title": "Methodological simplifications in radioimmunoassay of urinary aldosterone.", "content": "Simplification of radioimmunoassay procedures of urinary aldosterone-18-glucuronide was attempted, taking into consideration the aspects implied by the hydrolysis of urine and the assay itself. The procedure standardized for the hydrolysis step (samples diluted with a two-fold volume of 0.2 N HCl and incubated at 30 degrees C for 16-24 h) proved suitable in terms of practicability and accuracy. Aldosterone antisera, raised in the rabbit against an aldosterone-3-bovine albumin conjugate, were selected according to their specificity towards competing steroids. Depending on the characteristics of the antisera used, an assay of extracts, or even direct measurements of hydrolyzed urines excluding any extraction, were found to yield reliable results. In the case of a high-quality antiserum, evidence for the adequacy of assay on non-hydrolyzed urine extracts for the measurement of the excretion of unconjugated aldosterone was provided by some preliminary data. The results of the experiments, directed at the methodological and clinical validation of the simplified procedures, are reported and discussed in this paper.", "contents": "Methodological simplifications in radioimmunoassay of urinary aldosterone. Simplification of radioimmunoassay procedures of urinary aldosterone-18-glucuronide was attempted, taking into consideration the aspects implied by the hydrolysis of urine and the assay itself. The procedure standardized for the hydrolysis step (samples diluted with a two-fold volume of 0.2 N HCl and incubated at 30 degrees C for 16-24 h) proved suitable in terms of practicability and accuracy. Aldosterone antisera, raised in the rabbit against an aldosterone-3-bovine albumin conjugate, were selected according to their specificity towards competing steroids. Depending on the characteristics of the antisera used, an assay of extracts, or even direct measurements of hydrolyzed urines excluding any extraction, were found to yield reliable results. In the case of a high-quality antiserum, evidence for the adequacy of assay on non-hydrolyzed urine extracts for the measurement of the excretion of unconjugated aldosterone was provided by some preliminary data. The results of the experiments, directed at the methodological and clinical validation of the simplified procedures, are reported and discussed in this paper."}
{"id": "PMID:2398", "title": "[Studies on the activities of peptidases from human leucocytes, and human and guinea pig alveolar macrophages (author's transl)].", "content": "Peptidases activities were compared in human leucocytes, guinea pig and human alveolar macrophages. Seversl endo- and exopeptides were characterized; some of them were active at acid pH and others at neutral and alkaline pH. Leucocytes and alveolar macrophages had proteolygic activity for hemoglobin, fibrinogen, collagen and elastin. Using synthetic substrates, several enzymes were characterized: arylamidase, aminopeptidase, carboxypeptidases A and B and cathepsins A and C. The enzymatic activities were much higher in alveolar macrophages than in leucocytes.", "contents": "[Studies on the activities of peptidases from human leucocytes, and human and guinea pig alveolar macrophages (author's transl)]. Peptidases activities were compared in human leucocytes, guinea pig and human alveolar macrophages. Seversl endo- and exopeptides were characterized; some of them were active at acid pH and others at neutral and alkaline pH. Leucocytes and alveolar macrophages had proteolygic activity for hemoglobin, fibrinogen, collagen and elastin. Using synthetic substrates, several enzymes were characterized: arylamidase, aminopeptidase, carboxypeptidases A and B and cathepsins A and C. The enzymatic activities were much higher in alveolar macrophages than in leucocytes."}
{"id": "PMID:2401", "title": "Experience with a simple method for estrogen receptor assay in breast cancer.", "content": "A simple procedure for the assay of specific estrogen receptors in breast cancer tissue is described. Estrogen receptors were detected in 74% of primary tumors, 71% of skin metastases and 63% of lymph node metastases. Postmenopausal patients and younger oophorectomized women had estrogen receptor-containing tumors more frequently, and at higher levels, than uncastrated, premenopausal, patients. The stability of estrogen receptors was not affected by the transportation of samples from distant hospitals, providing that they were kept frozen in Tris buffer, pH 8.0, at all times.", "contents": "Experience with a simple method for estrogen receptor assay in breast cancer. A simple procedure for the assay of specific estrogen receptors in breast cancer tissue is described. Estrogen receptors were detected in 74% of primary tumors, 71% of skin metastases and 63% of lymph node metastases. Postmenopausal patients and younger oophorectomized women had estrogen receptor-containing tumors more frequently, and at higher levels, than uncastrated, premenopausal, patients. The stability of estrogen receptors was not affected by the transportation of samples from distant hospitals, providing that they were kept frozen in Tris buffer, pH 8.0, at all times."}
{"id": "PMID:2402", "title": "Immunological detection of isoferritins in normal human serum and tissue.", "content": "A method is described which permits the detection of isoferritins in normal human serum and tissues. The technique makes use of 125I-labelled monospecific anti-human-liver-ferritin antibody to demonstrate the isoferritins after isoelectric focussing of the purified ferritin in polyacrylamide gels. The organ-specific variation in tissue isoferritin profile previously reported in normal subjects has been confirmed by this technique using only 50 ng of each ferritin sample. Serum ferritin from normal healthy subjects was also shown to exhibit a microheterogeneity on isoelectric focussing; six clearly defined isoferritin peaks were detected in the pH range of 5.04 to 5.62. This isoferritin profile of normal serum contained isoferritins over the whole range of the various tissue isoferritins suggesting that a number of organs may contribute to the normal serum ferritin pool.", "contents": "Immunological detection of isoferritins in normal human serum and tissue. A method is described which permits the detection of isoferritins in normal human serum and tissues. The technique makes use of 125I-labelled monospecific anti-human-liver-ferritin antibody to demonstrate the isoferritins after isoelectric focussing of the purified ferritin in polyacrylamide gels. The organ-specific variation in tissue isoferritin profile previously reported in normal subjects has been confirmed by this technique using only 50 ng of each ferritin sample. Serum ferritin from normal healthy subjects was also shown to exhibit a microheterogeneity on isoelectric focussing; six clearly defined isoferritin peaks were detected in the pH range of 5.04 to 5.62. This isoferritin profile of normal serum contained isoferritins over the whole range of the various tissue isoferritins suggesting that a number of organs may contribute to the normal serum ferritin pool."}
{"id": "PMID:2403", "title": "Acceleration of autoimmunity in NZB/NZW F1 mice by graft-versus-host disease.", "content": "Chronic graft-versus-host (GVH) disease was induced in NZB/NZW F1 (B/W) hybrid female mice by the weekly injection of parental NZB spleen cells. Control mice received injections of syngeneic spleen cells only. The mice were assayed for antibodies to [3H]DNA and [3H]polyadenylic-polyuridylic acid by a cellulose ester filter radioimmunoassay, and for antibody to thymocytes by a cytotoxicity method. GVH disease accelerated the development of all three antibodies in B/W mice. In addition, sucrose density gradient ultracentrifugation of pooled sera suggested that an accelerated switch from 19S to 7S anti-DNA production may be an early effect of GVH. The mechanism of acceleration is discussed in terms of immunological and viral factors generated by the GVH reaction.", "contents": "Acceleration of autoimmunity in NZB/NZW F1 mice by graft-versus-host disease. Chronic graft-versus-host (GVH) disease was induced in NZB/NZW F1 (B/W) hybrid female mice by the weekly injection of parental NZB spleen cells. Control mice received injections of syngeneic spleen cells only. The mice were assayed for antibodies to [3H]DNA and [3H]polyadenylic-polyuridylic acid by a cellulose ester filter radioimmunoassay, and for antibody to thymocytes by a cytotoxicity method. GVH disease accelerated the development of all three antibodies in B/W mice. In addition, sucrose density gradient ultracentrifugation of pooled sera suggested that an accelerated switch from 19S to 7S anti-DNA production may be an early effect of GVH. The mechanism of acceleration is discussed in terms of immunological and viral factors generated by the GVH reaction."}
{"id": "PMID:2404", "title": "Lymphocyte subpopulations. Human red blood cell rosettes.", "content": "Human red blood cells (HRBC) even without prior neuraminidase treatment, could form rosettes with human peripheral blood lymphocytes in vitro. The optimum conditions for forming these rosettes were a pH of 7-0 and a medium with 5% bovine serum albumin (BSA). Rosette proportions became much less at a different pH or using lower concentrations of BSA, or replacing BSA with foetal calf sera (FCS) or human sera. Rosette formation was also promoted by prior treatment of HRBC or lymphocytes with neuraminidase. Mixed rosettes of HRBC and sheep red blood cells (SRBC) showed that HRBC receptors were detectable only on lymphocytes that possessed SRBC receptors, suggesting that HRBC rosette-forming cells were probably thymus-derived (T) cells. Next, the properties of human red blood cell (HRBC) and sheep red blood cell (SRBC) rosette-forming cells were investigated by comparing the ability of human peripheral blood lymphocytes to form these two types of rosettes after treatment with various inhibitory reagents. HRBC rosettes were relatively more resistant to inhibition with: (1) proteolytic agents, such as trypsin, alpha-chymotrypsin and pronase; (2) anti-thymocyte serum (ATS); (3) metabolic inhibitors, such as sodium azide and 2,4-dinitrophenol (DNP); (4) cytochalasin B. On further incubation after trypsinization, the lymphocytes recovered some ability to form SRBC rosettes, but continued to lose more of their capability to form HRBC rosettes. All these results were regarded as circumstantial evidence that the HRBC rosettes might represent a subpopulation of human T lymphocytes.", "contents": "Lymphocyte subpopulations. Human red blood cell rosettes. Human red blood cells (HRBC) even without prior neuraminidase treatment, could form rosettes with human peripheral blood lymphocytes in vitro. The optimum conditions for forming these rosettes were a pH of 7-0 and a medium with 5% bovine serum albumin (BSA). Rosette proportions became much less at a different pH or using lower concentrations of BSA, or replacing BSA with foetal calf sera (FCS) or human sera. Rosette formation was also promoted by prior treatment of HRBC or lymphocytes with neuraminidase. Mixed rosettes of HRBC and sheep red blood cells (SRBC) showed that HRBC receptors were detectable only on lymphocytes that possessed SRBC receptors, suggesting that HRBC rosette-forming cells were probably thymus-derived (T) cells. Next, the properties of human red blood cell (HRBC) and sheep red blood cell (SRBC) rosette-forming cells were investigated by comparing the ability of human peripheral blood lymphocytes to form these two types of rosettes after treatment with various inhibitory reagents. HRBC rosettes were relatively more resistant to inhibition with: (1) proteolytic agents, such as trypsin, alpha-chymotrypsin and pronase; (2) anti-thymocyte serum (ATS); (3) metabolic inhibitors, such as sodium azide and 2,4-dinitrophenol (DNP); (4) cytochalasin B. On further incubation after trypsinization, the lymphocytes recovered some ability to form SRBC rosettes, but continued to lose more of their capability to form HRBC rosettes. All these results were regarded as circumstantial evidence that the HRBC rosettes might represent a subpopulation of human T lymphocytes."}
{"id": "PMID:2405", "title": "Acetate intolerance during hemodialysis.", "content": "Acetate is frequently substituted for bicarbonate in hemodialysis solutions. Plasma acetate and bicarbonate concentrations were measured in nine patients with chronic renal failure undergoing hemodialysis with dialyzate containing acetate. In three patients (2 children and 1 adult) plasma acetate concentrations exceeded 15 mEq/liter during the dialysis. The mechanisms leading to acetate intolerance are probably multiple. It cannot be assumed that dialysis with acetate containing solutions will restore the buffer anion deficit characteristic of chronic renal failure.", "contents": "Acetate intolerance during hemodialysis. Acetate is frequently substituted for bicarbonate in hemodialysis solutions. Plasma acetate and bicarbonate concentrations were measured in nine patients with chronic renal failure undergoing hemodialysis with dialyzate containing acetate. In three patients (2 children and 1 adult) plasma acetate concentrations exceeded 15 mEq/liter during the dialysis. The mechanisms leading to acetate intolerance are probably multiple. It cannot be assumed that dialysis with acetate containing solutions will restore the buffer anion deficit characteristic of chronic renal failure."}
{"id": "PMID:2406", "title": "Effect of liver failure on the ventilatory response to hypoxia in man and the goat.", "content": "1. The ventilatory responses to transient and steady-state hypoxia were measured in ten patients with hepatic cirrhosis and in ten healthy control subjects. Successive measurements of these responses were also obtained in six goats before and after the experimental production of liver failure. Changes in the effect of steady-state hypoxia on the ventilatory response to hypercapnia were evaluated by successive studies in another goat. 2. In spite of a respiratory alkalosis during liver failure, the response to transient hypoxia was greater in the patients than in the control subjects. This response was increased after the onset of liver failure in all the goats. 3. In healthy humans and goats the responses to transient and steady-state hypoxia were similar in magnitude. During liver failure there was a disparity between the size of these responses, since the ventilatory increment evoked by steady-state hypoxia was unchanged in spite of the increase in response to transient hypoxia. Steady-state hypoxia consistently enhanced the ventilatory response to hypercapnia in a healthy goat, but frequently depressed the response to hypercapnia during liver failure. 4. The findings suggest that liver failure heightens the sensitivity of the peripheral chemoreceptors to the hypoxic stimulus, but may increase the tendency of the medullary centres to become depressed in hypoxia.", "contents": "Effect of liver failure on the ventilatory response to hypoxia in man and the goat. 1. The ventilatory responses to transient and steady-state hypoxia were measured in ten patients with hepatic cirrhosis and in ten healthy control subjects. Successive measurements of these responses were also obtained in six goats before and after the experimental production of liver failure. Changes in the effect of steady-state hypoxia on the ventilatory response to hypercapnia were evaluated by successive studies in another goat. 2. In spite of a respiratory alkalosis during liver failure, the response to transient hypoxia was greater in the patients than in the control subjects. This response was increased after the onset of liver failure in all the goats. 3. In healthy humans and goats the responses to transient and steady-state hypoxia were similar in magnitude. During liver failure there was a disparity between the size of these responses, since the ventilatory increment evoked by steady-state hypoxia was unchanged in spite of the increase in response to transient hypoxia. Steady-state hypoxia consistently enhanced the ventilatory response to hypercapnia in a healthy goat, but frequently depressed the response to hypercapnia during liver failure. 4. The findings suggest that liver failure heightens the sensitivity of the peripheral chemoreceptors to the hypoxic stimulus, but may increase the tendency of the medullary centres to become depressed in hypoxia."}
{"id": "PMID:2407", "title": "Ventilatory response to carbon dioxide in tetanus.", "content": "1. Ventilatory response to carbon dioxide was measured by the rebreathing technique in seven patients with mild tetanus during the disease state and after clinical recovery. 2. The ventilatory response to carbon dioxide was found to be decreased in the tetanus patients during the disease state with normal response after full clinical recovery. It is postulated that the restrictive ventilatory defect was responsible for the decreased ventilatory response to carbon dioxide.", "contents": "Ventilatory response to carbon dioxide in tetanus. 1. Ventilatory response to carbon dioxide was measured by the rebreathing technique in seven patients with mild tetanus during the disease state and after clinical recovery. 2. The ventilatory response to carbon dioxide was found to be decreased in the tetanus patients during the disease state with normal response after full clinical recovery. It is postulated that the restrictive ventilatory defect was responsible for the decreased ventilatory response to carbon dioxide."}
{"id": "PMID:2454", "title": "[Treatment of severe hypnotic poisoning with extracorporeal haemoperfusion (author's transl)].", "content": "Four patients with severe hypnotic intoxication, twice after suicidal intake of barbital, once of barbital, methaqualone and carbromal, and once of carbromal, were treated with six activated charcoal haemoperfusions. Three patients showed rapid improvement in the level of consciousness followed by complete recovery. One female patient died in cerebral coma due to complete acute cerebromalacia following hypoxia. Serious complications due to the haemoperfusion did not occur. Correct use of activated charcoal haemoperfusion enriches the therapeutic spectrum of severe exogenous intoxications.", "contents": "[Treatment of severe hypnotic poisoning with extracorporeal haemoperfusion (author's transl)]. Four patients with severe hypnotic intoxication, twice after suicidal intake of barbital, once of barbital, methaqualone and carbromal, and once of carbromal, were treated with six activated charcoal haemoperfusions. Three patients showed rapid improvement in the level of consciousness followed by complete recovery. One female patient died in cerebral coma due to complete acute cerebromalacia following hypoxia. Serious complications due to the haemoperfusion did not occur. Correct use of activated charcoal haemoperfusion enriches the therapeutic spectrum of severe exogenous intoxications."}
{"id": "PMID:2457", "title": "Failure to monoaminergic and cholinergic receptor blockers to prevent prostaglandin E2-induced luteinizing hormone release.", "content": "Receptor blocking drugs were used to determine whether adrenergic, dopaminergic, serotoninergic, or cholinergic synapses are involved in mediating the LH release induced by intraventricularly injected PGE2. Prostaglandin E2 (5mug) was injected into the 3rd ventricle (3rd V) of ovariectomized rats, and plasma LH concentrations before and after treatment were determined by radioimmunoassay. Phentolamine, 20 or 30 mug, or pronethalol, 20 mug (alpha and beta adrenergic receptor blockers, respectively) injected into the 3rd V failed to alter the elevation of plasma LH evoked by PGE2 injected into the ventricle 10 min later. Likewise, LH release following PGE2 was not changed when a dopaminergic blocker, pimozide (0.63 mg/kg, SC), was injected 2 h prior to PGE2. Two antagonists of serotonin, methysergide maleate (3 mg/kg ip) or cinanserin HC1 (1 mg/kg iv) given 2 h or 45 min before PGE2, respectively, failed to alter the action of PGE2. Atropine (100 or 250 mug) injected into the 3rd V 10 min prior to PGE2 was also ineffective in blocking the increase in plasma LH following PGE2. The results of this study indicate that the effect of PGE2 on LH release is not mediated by adrenergic, dopaminergic, serotoninergic, or cholinergic receptors. They also suggest that PGE2 is not acting trans-synaptically but probably directly on the LHRH neuron to induce the discharge of LHRH into the hypophysial portal vessels which then evokes release of LH from the adenohypophysis.", "contents": "Failure to monoaminergic and cholinergic receptor blockers to prevent prostaglandin E2-induced luteinizing hormone release. Receptor blocking drugs were used to determine whether adrenergic, dopaminergic, serotoninergic, or cholinergic synapses are involved in mediating the LH release induced by intraventricularly injected PGE2. Prostaglandin E2 (5mug) was injected into the 3rd ventricle (3rd V) of ovariectomized rats, and plasma LH concentrations before and after treatment were determined by radioimmunoassay. Phentolamine, 20 or 30 mug, or pronethalol, 20 mug (alpha and beta adrenergic receptor blockers, respectively) injected into the 3rd V failed to alter the elevation of plasma LH evoked by PGE2 injected into the ventricle 10 min later. Likewise, LH release following PGE2 was not changed when a dopaminergic blocker, pimozide (0.63 mg/kg, SC), was injected 2 h prior to PGE2. Two antagonists of serotonin, methysergide maleate (3 mg/kg ip) or cinanserin HC1 (1 mg/kg iv) given 2 h or 45 min before PGE2, respectively, failed to alter the action of PGE2. Atropine (100 or 250 mug) injected into the 3rd V 10 min prior to PGE2 was also ineffective in blocking the increase in plasma LH following PGE2. The results of this study indicate that the effect of PGE2 on LH release is not mediated by adrenergic, dopaminergic, serotoninergic, or cholinergic receptors. They also suggest that PGE2 is not acting trans-synaptically but probably directly on the LHRH neuron to induce the discharge of LHRH into the hypophysial portal vessels which then evokes release of LH from the adenohypophysis."}
{"id": "PMID:2458", "title": "Neurotransmitter regulation of growth hormone and ACTH in the rhesus monkey: effects of biogenic amines.", "content": "In an attempt to clarify the role of central neurotransmitters in GH and ACTH regulation, chair-adapted unanesthetized adult male rhesus monkeys and chronic indwelling intratrial cannulae were given 30 min infusions of various agonists known to affect central amines, and plasma samples were withdrawn for GH and cortisol determinations. Infusion of acid-saline vehicle alone had no significant effect on plasma GH or cortisol (P less than 0.05). L-Dihydroxyphenylalanine (L-Dopa) (4.5 and 45 mg/kg), but not apomorphine (7 mug/kg), a specific dopaminergic agonist, produced significant elevations of GH. Both noradrenergic (clonidine HCl, 1.5, 15, and 150 mug/kg, and D,L-threodihydroxyphenylserine (D,L-threodops) 90 mg/kg) and serotoninergic (5-hydroxy-L-tryptophan (5-HTP), 45 mg/kg) agonists induced significant GH responses. These findings suggest that GH is regulated in the rhesus monkey by noradrenergic and serotoninergic neurons, whereas participation of dopaminergic neurons has not been established. Significant cortisol responses were only observed following infusion of 5HTP (45 mg/kg). Dopaminergic and noradrenergic agonists not only failed to alter resting cortisol levels but also did not affect the cortisol response to 5-HTP. In the rhesus monkey serotoninergic mechanisms appear to be responsible for the regulation of resting cortisol levels. A catecholamine inhibitory mechanism was not demonstrated in this species.", "contents": "Neurotransmitter regulation of growth hormone and ACTH in the rhesus monkey: effects of biogenic amines. In an attempt to clarify the role of central neurotransmitters in GH and ACTH regulation, chair-adapted unanesthetized adult male rhesus monkeys and chronic indwelling intratrial cannulae were given 30 min infusions of various agonists known to affect central amines, and plasma samples were withdrawn for GH and cortisol determinations. Infusion of acid-saline vehicle alone had no significant effect on plasma GH or cortisol (P less than 0.05). L-Dihydroxyphenylalanine (L-Dopa) (4.5 and 45 mg/kg), but not apomorphine (7 mug/kg), a specific dopaminergic agonist, produced significant elevations of GH. Both noradrenergic (clonidine HCl, 1.5, 15, and 150 mug/kg, and D,L-threodihydroxyphenylserine (D,L-threodops) 90 mg/kg) and serotoninergic (5-hydroxy-L-tryptophan (5-HTP), 45 mg/kg) agonists induced significant GH responses. These findings suggest that GH is regulated in the rhesus monkey by noradrenergic and serotoninergic neurons, whereas participation of dopaminergic neurons has not been established. Significant cortisol responses were only observed following infusion of 5HTP (45 mg/kg). Dopaminergic and noradrenergic agonists not only failed to alter resting cortisol levels but also did not affect the cortisol response to 5-HTP. In the rhesus monkey serotoninergic mechanisms appear to be responsible for the regulation of resting cortisol levels. A catecholamine inhibitory mechanism was not demonstrated in this species."}
{"id": "PMID:2459", "title": "Adrenergic binding sites and enzyme activities in the heart of hyperthyroid rats.", "content": "In present study interactions of some adrenergic drugs with the binding of 3H-norepinephrine (NE) and response of some enzymatic systems in the heart of rats with pharmacological hyperthyroidism have been investigated. Binding of NE to cardiac particles was inhibited by isoproterenol, propranolol and in lower concentrations by another beta-blocking drug trimepranol both in control and hyperthyroid hearts in the same degree. However, after addition of nonradioactive  norepinephrine (10(-3) M) the degree of displacement was lower in hyperthyroid than in euthyroid group. Activity of adenylate cyclase was lower in hyperthyroid cardiac particles. This difference remained preserved after stimulation by norepinephrine or NaF. The activities of hormone-sensitive lipase and lipoprotein lipase were increased in preparation of hyperthyroid hearts. The phosphorylase \"a\" activity was also increased in hyperthyroid cardiac particles. There was no change in cardiac adrenergic binding sites properties in hyperthyroidism with the exception of less displacement of NE by nonlabelled hormone. The results indicate that the increased lipolytic and phosphorylase \"a\" activities in hyperthyroid hearts are not necessarily linked to elevated activity of adenylate cyclase.", "contents": "Adrenergic binding sites and enzyme activities in the heart of hyperthyroid rats. In present study interactions of some adrenergic drugs with the binding of 3H-norepinephrine (NE) and response of some enzymatic systems in the heart of rats with pharmacological hyperthyroidism have been investigated. Binding of NE to cardiac particles was inhibited by isoproterenol, propranolol and in lower concentrations by another beta-blocking drug trimepranol both in control and hyperthyroid hearts in the same degree. However, after addition of nonradioactive  norepinephrine (10(-3) M) the degree of displacement was lower in hyperthyroid than in euthyroid group. Activity of adenylate cyclase was lower in hyperthyroid cardiac particles. This difference remained preserved after stimulation by norepinephrine or NaF. The activities of hormone-sensitive lipase and lipoprotein lipase were increased in preparation of hyperthyroid hearts. The phosphorylase \"a\" activity was also increased in hyperthyroid cardiac particles. There was no change in cardiac adrenergic binding sites properties in hyperthyroidism with the exception of less displacement of NE by nonlabelled hormone. The results indicate that the increased lipolytic and phosphorylase \"a\" activities in hyperthyroid hearts are not necessarily linked to elevated activity of adenylate cyclase."}
{"id": "PMID:2460", "title": "Determination of total insulin (TIRI) in plasma of insulin-treated diabetics and newborn infants of insulin-treated diabetic mothers.", "content": "Plasma of insulin-treated diabetics and of newborn infants of insulin-treated diabetic mothers contains insulin antibodies which invalidates the radioimmunoassay of insulin. Therefore, the endogenous insulin antibody complex must be splitted at a pH lower than 5 and the total IRI (TIRI) is separated by ethanol extraction. It was investigated the recovery rate in dependence upon plasma volume used for extraction. By reduction of used plasma volume from 500 to 200 mul per extraction the recovery rate was increased from 65.1 +/- 8.4 to 88.3 +/- 4.2% (mean +/- SEM). The low plasma volume of 200 mul for TIRI extraction made it possible to determine TIRI during glucose loads of newborn infants. To eliminate different conditions of incubation for standard and unknown plasma samples the TIRI levels were computed by means of so-called \"extracted\" standard curve, obtained with extracted insulin from standard insulin dilution in insulin-free pooled human plasma. Using the described method a temporary regeneration of insulin secretion of a newly diagnosed juvenile diabetic after insulin treatment could be shown. In contrast to newborn infants of healthy mothers a biphasic/insulin release was found during the intravenous glucose loads in newborn infants of insulin-treated diabetic mothers.", "contents": "Determination of total insulin (TIRI) in plasma of insulin-treated diabetics and newborn infants of insulin-treated diabetic mothers. Plasma of insulin-treated diabetics and of newborn infants of insulin-treated diabetic mothers contains insulin antibodies which invalidates the radioimmunoassay of insulin. Therefore, the endogenous insulin antibody complex must be splitted at a pH lower than 5 and the total IRI (TIRI) is separated by ethanol extraction. It was investigated the recovery rate in dependence upon plasma volume used for extraction. By reduction of used plasma volume from 500 to 200 mul per extraction the recovery rate was increased from 65.1 +/- 8.4 to 88.3 +/- 4.2% (mean +/- SEM). The low plasma volume of 200 mul for TIRI extraction made it possible to determine TIRI during glucose loads of newborn infants. To eliminate different conditions of incubation for standard and unknown plasma samples the TIRI levels were computed by means of so-called \"extracted\" standard curve, obtained with extracted insulin from standard insulin dilution in insulin-free pooled human plasma. Using the described method a temporary regeneration of insulin secretion of a newly diagnosed juvenile diabetic after insulin treatment could be shown. In contrast to newborn infants of healthy mothers a biphasic/insulin release was found during the intravenous glucose loads in newborn infants of insulin-treated diabetic mothers."}
{"id": "PMID:2463", "title": "Glutamine synthetase, glutaminase and phosphodiesterase activities in brain under hypoxia: in vitro effect of cortisol, GABA and serotonin on glutamine synthetase.", "content": "The effect of hypobaric hypoxia on the activities of glutamine synthetase, glutaminase and cyclic 3'5' AMP phosphodiesterase in rat brain was studied after exposure to 25,000' for 6 h. Glutamine synthetase activity was increased in all the regions of brain studied, and addition of gamma amino butyric acid, serotonin and cortisol in vitro produced a differential response. Glutaminase activity decreased in the whole brain. Cyclic 3'5' AMP phosphodiesterase activity decreased in cerebellum, medulla, hypothalamus and pituitary showing an accumulation of cyclic 3'5' AMP in these regions. The results suggest that glutamine synthesis and degradation are regulated in the central nervous system by cyclic AMP and cortisol: Gamma aminoburyric acid and other compounds can modulate the activity of glutamine synthetase and glutaminase.", "contents": "Glutamine synthetase, glutaminase and phosphodiesterase activities in brain under hypoxia: in vitro effect of cortisol, GABA and serotonin on glutamine synthetase. The effect of hypobaric hypoxia on the activities of glutamine synthetase, glutaminase and cyclic 3'5' AMP phosphodiesterase in rat brain was studied after exposure to 25,000' for 6 h. Glutamine synthetase activity was increased in all the regions of brain studied, and addition of gamma amino butyric acid, serotonin and cortisol in vitro produced a differential response. Glutaminase activity decreased in the whole brain. Cyclic 3'5' AMP phosphodiesterase activity decreased in cerebellum, medulla, hypothalamus and pituitary showing an accumulation of cyclic 3'5' AMP in these regions. The results suggest that glutamine synthesis and degradation are regulated in the central nervous system by cyclic AMP and cortisol: Gamma aminoburyric acid and other compounds can modulate the activity of glutamine synthetase and glutaminase."}
{"id": "PMID:2464", "title": "Intermediates in the interconversion of acid and alkaline ferrihemoglobin. Structural and kinetic aspects.", "content": "The acid-alkaline pH-jump in suspension of crystalline sheep hemoglobin has been studied in the range of 5.95 to 8.94. Crystals suspended in 3.8 M Cs2SO4 show a rapid optical transition of half-time equal to or less than 2 ms. As the ammonia concentration is increased in the Cs2SO4-suspended crystals, a second optical transition is observed as a pseudo-first-order reaction, with a rate constant of between 10 and 15 s-1. The alkaline-acid pH-jump proceeds through a very rapid shift of the alkaline-acid equilibrium and is followed by a first-order dissociation constant between 9 and 12 s-1. The dissociation of the ammonia is biphasic, and the ratio between the fast and slow phases is 9.", "contents": "Intermediates in the interconversion of acid and alkaline ferrihemoglobin. Structural and kinetic aspects. The acid-alkaline pH-jump in suspension of crystalline sheep hemoglobin has been studied in the range of 5.95 to 8.94. Crystals suspended in 3.8 M Cs2SO4 show a rapid optical transition of half-time equal to or less than 2 ms. As the ammonia concentration is increased in the Cs2SO4-suspended crystals, a second optical transition is observed as a pseudo-first-order reaction, with a rate constant of between 10 and 15 s-1. The alkaline-acid pH-jump proceeds through a very rapid shift of the alkaline-acid equilibrium and is followed by a first-order dissociation constant between 9 and 12 s-1. The dissociation of the ammonia is biphasic, and the ratio between the fast and slow phases is 9."}
{"id": "PMID:2465", "title": "The reaction kinetics of fluoride and ammonia with acid and alkaline ferrimyoglobin in a crystalline state.", "content": "Differences between the reactivity of amorphous and crystalline myoglobin have been studied by the rapid-flow method combined with dual-wavelength spectrophotometry. The binding of ammonia to the hydroxide compound has a half-time of 55 ms. The reverse reaction has a half-time of 70 ms. At pH 7.0 the relative half-times of combination and dissociation with fluoride are 10 min for crystalline and 1.8 min for amorphous materials. Reactivity of the crystals to fluoride at pH 6.0 greatly increased as compared with pH 8.7. Half-time at pH 8.7 is 10 min, while at pH 6.0 the half-time is 2.5 s for the crystalline material and 1.4 s for the amorphous material. The exchange of fluoride by azide at pH 6.0 is 3.1-fold faster in amorphous material than in crystalline material.", "contents": "The reaction kinetics of fluoride and ammonia with acid and alkaline ferrimyoglobin in a crystalline state. Differences between the reactivity of amorphous and crystalline myoglobin have been studied by the rapid-flow method combined with dual-wavelength spectrophotometry. The binding of ammonia to the hydroxide compound has a half-time of 55 ms. The reverse reaction has a half-time of 70 ms. At pH 7.0 the relative half-times of combination and dissociation with fluoride are 10 min for crystalline and 1.8 min for amorphous materials. Reactivity of the crystals to fluoride at pH 6.0 greatly increased as compared with pH 8.7. Half-time at pH 8.7 is 10 min, while at pH 6.0 the half-time is 2.5 s for the crystalline material and 1.4 s for the amorphous material. The exchange of fluoride by azide at pH 6.0 is 3.1-fold faster in amorphous material than in crystalline material."}
{"id": "PMID:2466", "title": "Circular-dichroism and absorption spectroscopic studies on specific aromatic residues involved in the different modes of aggregation of tobacco-mosaic-virus protein.", "content": "Conformational changes accompanying the different modes of aggregation of tobacco mosaic virus protein (TMV-protein) were investigated using circular dichroism (CD) and absorption difference spectra in the range of aromatic absorption. Comparing wild-type protein and mutant Ni 2068 (Tyr-139 leads to Cys-139) a tentative localization of aromatic amino acids in the three-dimensional structure is rendered possible. In all modes of aggregation the CD spectra are determined by intrasubunit interactions between aromatic residues, in particular Trp-17 and Trp-52 as well as Tyr-70, Tyr-72 and Tyr-139. The Trp-17-Trp-52 interaction was found to be highly sensitive towards changes of the quaternary structure especially with respect to helical aggregates. This suggests that the environment of the two tryptophan residues is of crucial importance in the three-dimensional structure of the subunit; in the course of aggregation intersubunit interactions compete with the specific intrasubunit Trp-17--Trp52 interactions. It is suggested that Try-70 and Tyr-72 form hydrogen bonds in a strongly hydrophobic environment. Formation of the double disc decreases the rotatory strength, pointing to an increase in conformational flexibility. Spectroscopic and chemical evidence prove that Tyr-70, Tyr-72 and Tyr-139 are in close neighbourhood. Double disc formation by lowering the pH (pH 8 LEADS TO 6.9, I = 0.1 M) or increasing the ionic strength (pH 8, I = 0.1 LEADS TO 0.6 M) is reflected by identical spectral effects in the environment of Tyr-70 - Tyr-72. However the interaction between Trp-17 and Trp-52 indicates significant differences in the conformation which may be important for the formation of higher aggregates, i.e. 'lockwashers', helices, and 'stacked discs'.", "contents": "Circular-dichroism and absorption spectroscopic studies on specific aromatic residues involved in the different modes of aggregation of tobacco-mosaic-virus protein. Conformational changes accompanying the different modes of aggregation of tobacco mosaic virus protein (TMV-protein) were investigated using circular dichroism (CD) and absorption difference spectra in the range of aromatic absorption. Comparing wild-type protein and mutant Ni 2068 (Tyr-139 leads to Cys-139) a tentative localization of aromatic amino acids in the three-dimensional structure is rendered possible. In all modes of aggregation the CD spectra are determined by intrasubunit interactions between aromatic residues, in particular Trp-17 and Trp-52 as well as Tyr-70, Tyr-72 and Tyr-139. The Trp-17-Trp-52 interaction was found to be highly sensitive towards changes of the quaternary structure especially with respect to helical aggregates. This suggests that the environment of the two tryptophan residues is of crucial importance in the three-dimensional structure of the subunit; in the course of aggregation intersubunit interactions compete with the specific intrasubunit Trp-17--Trp52 interactions. It is suggested that Try-70 and Tyr-72 form hydrogen bonds in a strongly hydrophobic environment. Formation of the double disc decreases the rotatory strength, pointing to an increase in conformational flexibility. Spectroscopic and chemical evidence prove that Tyr-70, Tyr-72 and Tyr-139 are in close neighbourhood. Double disc formation by lowering the pH (pH 8 LEADS TO 6.9, I = 0.1 M) or increasing the ionic strength (pH 8, I = 0.1 LEADS TO 0.6 M) is reflected by identical spectral effects in the environment of Tyr-70 - Tyr-72. However the interaction between Trp-17 and Trp-52 indicates significant differences in the conformation which may be important for the formation of higher aggregates, i.e. 'lockwashers', helices, and 'stacked discs'."}
{"id": "PMID:2467", "title": "Characterization of the oxygenase activity in a mutant of Chlamydomonas reinhardi exhibiting altered ribulosebisphosphate carboxylase.", "content": "A previously described Mendelian mutant of Chlamydomonas reinhardi, ac i72, exhibiting altered ribulosebisphosphate carboxylase activity and unable to grow on minimal medium is examined for changes in ribulosebisphosphate oxygenase activity. The ribulosebisphosphate oxygenase activity of the enzyme purified from both wild type and ac i72 is compared over a pH range from 7.0 to 9.5. Both enzymes exhibit maximum activity at pH 9.0. However, the ac i72 enzyme is twice as active as the wild type enzyme at a physiological pH of 7.0. The studies in vivo of the products of CO2 fixation of ac i72 and wild type cells in the presence of high and low O2 concentration shows that due to a lower level of carboxylation, the ac i72 cells fix CO2 at half the rate of wild type cells. In ac i72, 24% of the photosynthetically fixed 14C is channelled into the water-soluble fraction as opposed to 6% in wild type. Thin-layer chromatography of the water-soluble fraction showed extensive accumulation of components of the glycolate pathway in ac i72 as compared to wild type. This indicates that the oxygenase activity of the enzyme prevails in ac i72 in vivo. Since a high concentration of glycolate is toxic to cells of C. reinhardi, the high oxygenase activity of ac i72 provides an explanation for the inability of ac i72 to grow phototrophically even though its rate of CO2 fixation is half that of wild type. This toxicity to glycolate is overcome by growth under amber illumination or low O2 concentration.", "contents": "Characterization of the oxygenase activity in a mutant of Chlamydomonas reinhardi exhibiting altered ribulosebisphosphate carboxylase. A previously described Mendelian mutant of Chlamydomonas reinhardi, ac i72, exhibiting altered ribulosebisphosphate carboxylase activity and unable to grow on minimal medium is examined for changes in ribulosebisphosphate oxygenase activity. The ribulosebisphosphate oxygenase activity of the enzyme purified from both wild type and ac i72 is compared over a pH range from 7.0 to 9.5. Both enzymes exhibit maximum activity at pH 9.0. However, the ac i72 enzyme is twice as active as the wild type enzyme at a physiological pH of 7.0. The studies in vivo of the products of CO2 fixation of ac i72 and wild type cells in the presence of high and low O2 concentration shows that due to a lower level of carboxylation, the ac i72 cells fix CO2 at half the rate of wild type cells. In ac i72, 24% of the photosynthetically fixed 14C is channelled into the water-soluble fraction as opposed to 6% in wild type. Thin-layer chromatography of the water-soluble fraction showed extensive accumulation of components of the glycolate pathway in ac i72 as compared to wild type. This indicates that the oxygenase activity of the enzyme prevails in ac i72 in vivo. Since a high concentration of glycolate is toxic to cells of C. reinhardi, the high oxygenase activity of ac i72 provides an explanation for the inability of ac i72 to grow phototrophically even though its rate of CO2 fixation is half that of wild type. This toxicity to glycolate is overcome by growth under amber illumination or low O2 concentration."}
{"id": "PMID:2468", "title": "An intracellular endonuclease of Bacillus subtilis specific for single-stranded DNA.", "content": "We have fractionated from extracts of Bacillus subtilis the DNase activity specific for single-stranded DNA; the activity separates in two main fractions on Sephadex G-200, a larger one (Mr greater than 400 000) and a smaller one (Mr approximately 30 000). We have purified the smaller, more abundant fraction nearly 3000-fold. The purified enzyme has a pH optimum close to 8, is activated by Ca2+, and is inhibited by EDTA; the enzyme hydrolyses single-stranded DNA at a rate approximately 40 times greater than double-stranded DNA. The mode of action is endonucleolytic on both substrates, but the possiblility that the two activities may reside on different molecules is not ruled out. The products have 5'-P and 3'-OH ends. The enzyme is different from those purified from the culture media of the same organism in several respects; the latter are all extracellular enzymes, they are not specific for single-stranded DNA (except one) and have all an exonucleolytic mode of action.", "contents": "An intracellular endonuclease of Bacillus subtilis specific for single-stranded DNA. We have fractionated from extracts of Bacillus subtilis the DNase activity specific for single-stranded DNA; the activity separates in two main fractions on Sephadex G-200, a larger one (Mr greater than 400 000) and a smaller one (Mr approximately 30 000). We have purified the smaller, more abundant fraction nearly 3000-fold. The purified enzyme has a pH optimum close to 8, is activated by Ca2+, and is inhibited by EDTA; the enzyme hydrolyses single-stranded DNA at a rate approximately 40 times greater than double-stranded DNA. The mode of action is endonucleolytic on both substrates, but the possiblility that the two activities may reside on different molecules is not ruled out. The products have 5'-P and 3'-OH ends. The enzyme is different from those purified from the culture media of the same organism in several respects; the latter are all extracellular enzymes, they are not specific for single-stranded DNA (except one) and have all an exonucleolytic mode of action."}
{"id": "PMID:2469", "title": "Guanylate cyclase: assay and properties of the particulate and supernatant enzymes in mouse parotid.", "content": "A new, very sensitive, rapid and reliable assay for guanylate cyclase has been established based on conversion of [32P]GTP to [32P]guanosine 3':5'-monophosphate and its separation on Dowex 50 and aluminium oxide columns. The optimum conditions for the assay of mouse parotid guanylate cyclase have been established and using this procedure the properties of the enzyme have been investigated. The enzyme was found in both the particulate and supernatant fractions. The particulate enzyme was activated 12-fold by Triton X-100 and the supernatant enzyme activity increased 2-fold. In the presence of detergent guanylate cyclase activity was distributed 85% in the particulate and 15% in the supernatant fractions, respectively. The particulate activity was localised in a plasma membrane fraction. Guanylate cyclase activity was also assayed in a wide variety of other tissues. In all cases enzymatic activity was found in both the particulate and supernatant fractions. The distribution varied with the tissue but only the intestinal mucosa had a greater proportion of total guanylate cyclase activity in the particulate fraction than the parotid. The two enzymes showed some similar properties. Their pH optima were pH 7.4, both enzymes were inhibited by ATP, dATP, dGTP and ITP, required Mn2+ for activity and plots of activity versus Mn2+ concentration were sigmoidal. However, in many properties the enzymes were dissimilar. The ratios of Mn2+ to GTP for optimum activity were 4 and 1.5 for the supernatant and plasma-bound enzymes, respectively. The slope of Hill plots for the supernatant enzyme with varying Mn2+ was 2. The particulate enzyme plots also had a slope of 2 at low Mn2+ concentration but at higher concentrations (above 0.7 mM) the Hill coefficient shifted abruptly to 4. Calcium ions reduced sigmoidicity of the kinetics lowering the Hill coefficient, activated the enzyme at all Mn2+ concentrations but had no effect on the Mn2+:GTP ratio with the supernatant enzyme while with the plasma membrane enzyme Ca2+ had no effect on the sigmoid form of the kinetics at low Mn2+ but prevented the shift to a greater Hill coefficient at higher Mn2+, inhibited the activity at low Mn2+ and shifted the Mn2+:GTP optimum ratio to 4. For the particulate enzyme plots of activity versus GTP concentration were sigmoid (n = 1.3), while the supernatant enzyme exhibited hyperbolic kinetics.", "contents": "Guanylate cyclase: assay and properties of the particulate and supernatant enzymes in mouse parotid. A new, very sensitive, rapid and reliable assay for guanylate cyclase has been established based on conversion of [32P]GTP to [32P]guanosine 3':5'-monophosphate and its separation on Dowex 50 and aluminium oxide columns. The optimum conditions for the assay of mouse parotid guanylate cyclase have been established and using this procedure the properties of the enzyme have been investigated. The enzyme was found in both the particulate and supernatant fractions. The particulate enzyme was activated 12-fold by Triton X-100 and the supernatant enzyme activity increased 2-fold. In the presence of detergent guanylate cyclase activity was distributed 85% in the particulate and 15% in the supernatant fractions, respectively. The particulate activity was localised in a plasma membrane fraction. Guanylate cyclase activity was also assayed in a wide variety of other tissues. In all cases enzymatic activity was found in both the particulate and supernatant fractions. The distribution varied with the tissue but only the intestinal mucosa had a greater proportion of total guanylate cyclase activity in the particulate fraction than the parotid. The two enzymes showed some similar properties. Their pH optima were pH 7.4, both enzymes were inhibited by ATP, dATP, dGTP and ITP, required Mn2+ for activity and plots of activity versus Mn2+ concentration were sigmoidal. However, in many properties the enzymes were dissimilar. The ratios of Mn2+ to GTP for optimum activity were 4 and 1.5 for the supernatant and plasma-bound enzymes, respectively. The slope of Hill plots for the supernatant enzyme with varying Mn2+ was 2. The particulate enzyme plots also had a slope of 2 at low Mn2+ concentration but at higher concentrations (above 0.7 mM) the Hill coefficient shifted abruptly to 4. Calcium ions reduced sigmoidicity of the kinetics lowering the Hill coefficient, activated the enzyme at all Mn2+ concentrations but had no effect on the Mn2+:GTP ratio with the supernatant enzyme while with the plasma membrane enzyme Ca2+ had no effect on the sigmoid form of the kinetics at low Mn2+ but prevented the shift to a greater Hill coefficient at higher Mn2+, inhibited the activity at low Mn2+ and shifted the Mn2+:GTP optimum ratio to 4. For the particulate enzyme plots of activity versus GTP concentration were sigmoid (n = 1.3), while the supernatant enzyme exhibited hyperbolic kinetics."}
{"id": "PMID:2470", "title": "Influence of unsaturated fatty acids in chloroplasts. Shift of the pH optimum of electron flow and relations to deltapH, thylakoid internal pH and proton uptake.", "content": "Linolenic acid (C18:3) is the main endogenous unsaturated fatty acid of thylakoid membrane lipids, and seems in its free form to exert significant effects on the structure and function of photosynthetic membranes. In this investigation the effect of linolenic acid was studied at various pH values on the electron flow rate in isolated spinach chloroplasts and related to deltapH, the proton pump and the pH of the inner thylakoid space (pHi). The deltapH and pHi were estimated from the extent of the fluorescence quenching of 9-aminoacridine. Linolenic acid caused a shift (approximately one unit) of the pH optimum for electron flow toward acidity in the following systems: (a) photosystems II + I (from H2O to NADP+ or to 2,6-dichlorophenolindophenol) coupled or non-coupled; (b) photosystem II (from H2O to 2,6-dichlorophenolindophenol in the presence of dibromothymoquinone). In photosystem I conditions (phenazine methosulphate), the deltapH of the control increased as a function of external pHo with a maximum around pH 8.8. When linolenic acid was added, the deltapH dropped, but its optimum was shifted toward more acidic pHo. The same phenomena were also observed in photosytems II + I (from H2O to ferricyanide) and in photosystem II conditions (from H2O to ferricyanide in the presence of dibromothymoquinone). However, the deltapH was smaller and the sensitivity of the proton gradient toward linolenic acid was eventually higher than for photosystem I electron flow activity. The proton pump which might be considered as a measure of the internal buffering capacity of thylakoids was optimum at pHo, 6.7 in the controls. An addition of linolenic acid diminished the proton pump and shifted its optimum toward higher pHo. As a consequence, pHi increased when pHo was raised. At the optimal pHo 8.6 to 9, pHi were 5 to 5.5. Additions of increasing concentrations of linolenic acid displaced the curves toward higher pHi. A decrease of pHo was therefore required to maintain the pHi in the range of 5-5.5 for maximum electron flow. In conclusion, the electron flow activity seems to be delicately controlled by the proton pump (buffer capacity), deltapH, pHi and pHo. Fatty acids damage the membrane integrity in such a way that the subtile equilibrium between the factors is disturbed.", "contents": "Influence of unsaturated fatty acids in chloroplasts. Shift of the pH optimum of electron flow and relations to deltapH, thylakoid internal pH and proton uptake. Linolenic acid (C18:3) is the main endogenous unsaturated fatty acid of thylakoid membrane lipids, and seems in its free form to exert significant effects on the structure and function of photosynthetic membranes. In this investigation the effect of linolenic acid was studied at various pH values on the electron flow rate in isolated spinach chloroplasts and related to deltapH, the proton pump and the pH of the inner thylakoid space (pHi). The deltapH and pHi were estimated from the extent of the fluorescence quenching of 9-aminoacridine. Linolenic acid caused a shift (approximately one unit) of the pH optimum for electron flow toward acidity in the following systems: (a) photosystems II + I (from H2O to NADP+ or to 2,6-dichlorophenolindophenol) coupled or non-coupled; (b) photosystem II (from H2O to 2,6-dichlorophenolindophenol in the presence of dibromothymoquinone). In photosystem I conditions (phenazine methosulphate), the deltapH of the control increased as a function of external pHo with a maximum around pH 8.8. When linolenic acid was added, the deltapH dropped, but its optimum was shifted toward more acidic pHo. The same phenomena were also observed in photosytems II + I (from H2O to ferricyanide) and in photosystem II conditions (from H2O to ferricyanide in the presence of dibromothymoquinone). However, the deltapH was smaller and the sensitivity of the proton gradient toward linolenic acid was eventually higher than for photosystem I electron flow activity. The proton pump which might be considered as a measure of the internal buffering capacity of thylakoids was optimum at pHo, 6.7 in the controls. An addition of linolenic acid diminished the proton pump and shifted its optimum toward higher pHo. As a consequence, pHi increased when pHo was raised. At the optimal pHo 8.6 to 9, pHi were 5 to 5.5. Additions of increasing concentrations of linolenic acid displaced the curves toward higher pHi. A decrease of pHo was therefore required to maintain the pHi in the range of 5-5.5 for maximum electron flow. In conclusion, the electron flow activity seems to be delicately controlled by the proton pump (buffer capacity), deltapH, pHi and pHo. Fatty acids damage the membrane integrity in such a way that the subtile equilibrium between the factors is disturbed."}
{"id": "PMID:2471", "title": "Uronic acid dehydrogenase from Pseudomonas syringae. Purification and properties.", "content": "1. Uronic acid dehydrogenase was purified to homogeneity. After a 338-fold purification a yield of 16% was achieved with a specific activity of 81 mumol NADH formed min-1 mg protein-1. 2. The purity of the enzyme was controlled by disc electrophoresis, sodium dodecylsulfate electrophoresis and ultracentrifugation. 3. A molecular weight of 60 000 was determined by gel chromatography and by ultracentrifugation. 4. The native enzyme is composed of two subunits, their molecular weight being 30 000 as estimated by sodium dodecylsulfate electrophoresis. The subunits as such are inactive. 5. The absorption spectrum with a maximum at 278 nm shows no evidence for a prosthetic group. 6. For catalytic activity no SH groups and no metals seem to be necessary. 7. The Michaelis constants determined with the pure enzyme are for glucuronic acid Km = 0.37 mM, galacturonic acid Km = 54 muM and NAD+ (with glucuronic acid) Km = 80 muM. 8. A weak reverse reaction could be observed with glucaric acid lactones at acidic pH. 9. NADH is competitive with NAD+. The inhibitor constant is Ki = 60 muM. 10. The NAD+ binding site seems to be of lower specificity than the uronic acid binding site.", "contents": "Uronic acid dehydrogenase from Pseudomonas syringae. Purification and properties. 1. Uronic acid dehydrogenase was purified to homogeneity. After a 338-fold purification a yield of 16% was achieved with a specific activity of 81 mumol NADH formed min-1 mg protein-1. 2. The purity of the enzyme was controlled by disc electrophoresis, sodium dodecylsulfate electrophoresis and ultracentrifugation. 3. A molecular weight of 60 000 was determined by gel chromatography and by ultracentrifugation. 4. The native enzyme is composed of two subunits, their molecular weight being 30 000 as estimated by sodium dodecylsulfate electrophoresis. The subunits as such are inactive. 5. The absorption spectrum with a maximum at 278 nm shows no evidence for a prosthetic group. 6. For catalytic activity no SH groups and no metals seem to be necessary. 7. The Michaelis constants determined with the pure enzyme are for glucuronic acid Km = 0.37 mM, galacturonic acid Km = 54 muM and NAD+ (with glucuronic acid) Km = 80 muM. 8. A weak reverse reaction could be observed with glucaric acid lactones at acidic pH. 9. NADH is competitive with NAD+. The inhibitor constant is Ki = 60 muM. 10. The NAD+ binding site seems to be of lower specificity than the uronic acid binding site."}
{"id": "PMID:2472", "title": "The purification and properties of the trimethoprim-resistant dihydrofolate reductase mediated by the R-factor, R388.", "content": "The R-factor R388 mediates the production of a trimethoprim-resistant dihydrofolate reductase. This enzyme has a different molecular weight and pH profile to the trimethoprim-sensitive enzyme of the Escherichia coli host. The R-factor mediated enzyme was separated completely from the host E. coli enzyme by DEAE-cellulose ion-exchange chromatography. The purified R-factor enzyme was about 20 000 times less susceptible to trimethoprim than the E. coli enzyme and although it was inhibited competitively by trimethoprim, its inhibitor constant (Ki) was 20 000 times greater than that of the host enzyme. The R388 and E. coli enzymes also differed in their substrate specificity requirements. In addition, the R388 enzyme suprisingly conferred high level resistance to the broad spectrum dihydrofolate reductase inhibitor, amethopterin. The possible origins of the R388 enzyme are discussed.", "contents": "The purification and properties of the trimethoprim-resistant dihydrofolate reductase mediated by the R-factor, R388. The R-factor R388 mediates the production of a trimethoprim-resistant dihydrofolate reductase. This enzyme has a different molecular weight and pH profile to the trimethoprim-sensitive enzyme of the Escherichia coli host. The R-factor mediated enzyme was separated completely from the host E. coli enzyme by DEAE-cellulose ion-exchange chromatography. The purified R-factor enzyme was about 20 000 times less susceptible to trimethoprim than the E. coli enzyme and although it was inhibited competitively by trimethoprim, its inhibitor constant (Ki) was 20 000 times greater than that of the host enzyme. The R388 and E. coli enzymes also differed in their substrate specificity requirements. In addition, the R388 enzyme suprisingly conferred high level resistance to the broad spectrum dihydrofolate reductase inhibitor, amethopterin. The possible origins of the R388 enzyme are discussed."}
{"id": "PMID:2473", "title": "Glycosaminoglycan biosynthesis in arterial wall. Hexosaminyltransferase and glucuronyltransferase in cell membranes of aortic media-intima.", "content": "Hexosaminyltransferase and glucuronyltransferase are well known for their role in the biosynthesis of proteoglycans. These two enzymes are characterized in rough and smooth membranes, obtained following subcellular fractionation of aortic media-intima. They require the presence of Mn2+ or Mg2+ for activity. The optimum concentration for these two cations is 5 mM. The optimum pH for hexosaminyltransferase and glucuronyltransferase is approximately 6.8 in Tris buffer, and their optimum temperature is 30 degrees C. Hexosaminyltransferase has an apparent Km of 0.27 nM. Glucuronyltransferase has an apparent Km of 0.21 nM. Uptake of labeled sugars by endogenous proteoglycans is inhibited by puromycin. Hexosaminyltransferase and glucuronyltransferase are present in both rough and smooth submicrosomal fractions. The different endogenous glycosaminoglycans are labeled during our incubation experiments. The greatest incorporation is noted for hyaluronic acid and heparan sulfate; the least is seen for chondroitin sulfate. The results obtained in vitro for incorporation of labeled precursors into endogenous proteoglycans are consistent with those observed during the study in vivo of the turnover of these macromolecules.", "contents": "Glycosaminoglycan biosynthesis in arterial wall. Hexosaminyltransferase and glucuronyltransferase in cell membranes of aortic media-intima. Hexosaminyltransferase and glucuronyltransferase are well known for their role in the biosynthesis of proteoglycans. These two enzymes are characterized in rough and smooth membranes, obtained following subcellular fractionation of aortic media-intima. They require the presence of Mn2+ or Mg2+ for activity. The optimum concentration for these two cations is 5 mM. The optimum pH for hexosaminyltransferase and glucuronyltransferase is approximately 6.8 in Tris buffer, and their optimum temperature is 30 degrees C. Hexosaminyltransferase has an apparent Km of 0.27 nM. Glucuronyltransferase has an apparent Km of 0.21 nM. Uptake of labeled sugars by endogenous proteoglycans is inhibited by puromycin. Hexosaminyltransferase and glucuronyltransferase are present in both rough and smooth submicrosomal fractions. The different endogenous glycosaminoglycans are labeled during our incubation experiments. The greatest incorporation is noted for hyaluronic acid and heparan sulfate; the least is seen for chondroitin sulfate. The results obtained in vitro for incorporation of labeled precursors into endogenous proteoglycans are consistent with those observed during the study in vivo of the turnover of these macromolecules."}
{"id": "PMID:2474", "title": "A study of the lysyl residues in the basic pancreatic trypsin inhibitor using 1H nuclear magnetic resonance at 360 Mhz.", "content": "Fourier transform 1H nuclear magnetic resonance (NMR) experiments at 360 MHz using convolution difference techniques to improve the spectral resolution were employed to investigate the resonances of the lysyl residues in bovine pancreatic trypsin inhibitor. The observations in both native protein and in chemically modified protein containing Nepsilon-dimethyllsysine show that three of the four lysines extend predominantly freely into the solvent, whereas lysine-41 is involved in an intramolecular interaction with tyrosine-10. Since in the single crystal structure tyrosine-10 is involved in an intermolecular interaction with arginine-42 of the neighboring protein molecule, the NMR data thus reveal a local conformation difference for bovine pancreatic trypsin inhibitor in solution and in the crystalline form which appears to result primarily from intermolecular interaction in the crystal lattice.", "contents": "A study of the lysyl residues in the basic pancreatic trypsin inhibitor using 1H nuclear magnetic resonance at 360 Mhz. Fourier transform 1H nuclear magnetic resonance (NMR) experiments at 360 MHz using convolution difference techniques to improve the spectral resolution were employed to investigate the resonances of the lysyl residues in bovine pancreatic trypsin inhibitor. The observations in both native protein and in chemically modified protein containing Nepsilon-dimethyllsysine show that three of the four lysines extend predominantly freely into the solvent, whereas lysine-41 is involved in an intramolecular interaction with tyrosine-10. Since in the single crystal structure tyrosine-10 is involved in an intermolecular interaction with arginine-42 of the neighboring protein molecule, the NMR data thus reveal a local conformation difference for bovine pancreatic trypsin inhibitor in solution and in the crystalline form which appears to result primarily from intermolecular interaction in the crystal lattice."}
{"id": "PMID:2475", "title": "Effect of triiodothyronine on rat liver chromatin protein kinase.", "content": "1. Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2. Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32P when incubated with [gamma-32P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins.", "contents": "Effect of triiodothyronine on rat liver chromatin protein kinase. 1. Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2. Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32P when incubated with [gamma-32P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins."}
{"id": "PMID:2476", "title": "Subcellular distribution of histone-degrading enzyme activities from rat liver.", "content": "Chromatin prepared from liver tissue contains a histone-degrading enzyme activity with a pH optimum of 7.5-8.0, whereas chromatin isolated from purified nuclei is devoid of it. The histone-degrading enzyme activity was assayed with radioactively labelled total histones from Ehrlich ascites tumor cells. Among the different subcellular fractions assayed, only lysosomes and mitochondria exhibited histone-degrading enzymes. A pH optimum around 4.0-5.0 was found for the lysosomal fraction, whereas 7.5-8.0 has been found for mitochondria. Binding studies of frozen and thawed lysosomes or mitochondria to proteinase-free chromatin demonstrate that the proteinase associated with chromatin isolated from frozen tissue originates from damaged mitochondria. The protein degradation patterns obtained after acrylamide gel electrophoresis are similar for the chromatin-associated and the mitochondrial proteinase and different from that obtained after incubation with lysosomes. The chromatin-associated proteinase as well as the mitochondrial proteinase are strongly inhibited by 1.0 mM phenylmethanesulfonyl fluoride. Weak inhibition is found for lysosomal proteinases at pH 5. Kallikrein-trypsin inhibitor, however, inhibits lysosomal proteinase activity and has no effect on either chromatin-associated or mitochondrial proteinases. The higher template activity of chromatin isolated from a total homogenate compared to chromatin prepared from nuclei may be due to the presence of this histone-degrading enzyme activity.", "contents": "Subcellular distribution of histone-degrading enzyme activities from rat liver. Chromatin prepared from liver tissue contains a histone-degrading enzyme activity with a pH optimum of 7.5-8.0, whereas chromatin isolated from purified nuclei is devoid of it. The histone-degrading enzyme activity was assayed with radioactively labelled total histones from Ehrlich ascites tumor cells. Among the different subcellular fractions assayed, only lysosomes and mitochondria exhibited histone-degrading enzymes. A pH optimum around 4.0-5.0 was found for the lysosomal fraction, whereas 7.5-8.0 has been found for mitochondria. Binding studies of frozen and thawed lysosomes or mitochondria to proteinase-free chromatin demonstrate that the proteinase associated with chromatin isolated from frozen tissue originates from damaged mitochondria. The protein degradation patterns obtained after acrylamide gel electrophoresis are similar for the chromatin-associated and the mitochondrial proteinase and different from that obtained after incubation with lysosomes. The chromatin-associated proteinase as well as the mitochondrial proteinase are strongly inhibited by 1.0 mM phenylmethanesulfonyl fluoride. Weak inhibition is found for lysosomal proteinases at pH 5. Kallikrein-trypsin inhibitor, however, inhibits lysosomal proteinase activity and has no effect on either chromatin-associated or mitochondrial proteinases. The higher template activity of chromatin isolated from a total homogenate compared to chromatin prepared from nuclei may be due to the presence of this histone-degrading enzyme activity."}
{"id": "PMID:2477", "title": "Anion and amine uptake and uncoupling in submitochondrial particles.", "content": "1. Unlike chloroplasts, submitochondrial particles are not uncoupled by nigericin + KCl or NH4Cl. Also the uncoupling effect of lipophilic anions is largely independent of the addition of weak bases. 2. Low concentrations of permeant anions cause a shift of the steady-state energy level rather than a cycle of energy utilization. The degree of inhibition of ATP synthesis by tetraphenylboron is larger than required for the uptake of the anion. 3. Lipophilic anions such as bromthymolblue, bromcresolpurple, and 8-anilino-1-napthalene sulphonate cause a pH-independent, 50% uncoupling in submitochondrial particles at concentrations of 3, 30 and 30 muM, respectively. The passive interaction of bromthymolblue and bromcresolpurple appears as a pH-dependent distribution between two pHases. ATP causes a pH-independent slight shift in the anion distribution, with negligible anion accumulation. 4. Addition of amines to energized submitochondrial particles results in two types of effects; uptake of amines and uncoupling. While in chloroplasts amine uptake and uncoupling are closely associated, this is not the case in submitochondrial particles. The uncoupling effect is observed only with lipophilic and not with hydrophilic amines, and the degree of uncoupling increases with the lipophilicity of the amines. The amine uptake, on the other hand, is accompanied by negligible uncoupling. 5. While the uptake of amines is dependent on the presence of non-permeant anions, such as Cl-, the uncoupling effect is independent of Cl-. Furthermore the amine uncoupling is markedly enhanced by lipophilic anions. 6. The view is discussed that the uncoupling effect of lipophilic anions and lipophilic amines in submitochondrial particles is due to a catalytic energy dissipation rather than to a stoichiometry energy utilization. The molecular mechanism of uncoupling presumably involves a cycling of charges after a perturbation of the membrane structure.", "contents": "Anion and amine uptake and uncoupling in submitochondrial particles. 1. Unlike chloroplasts, submitochondrial particles are not uncoupled by nigericin + KCl or NH4Cl. Also the uncoupling effect of lipophilic anions is largely independent of the addition of weak bases. 2. Low concentrations of permeant anions cause a shift of the steady-state energy level rather than a cycle of energy utilization. The degree of inhibition of ATP synthesis by tetraphenylboron is larger than required for the uptake of the anion. 3. Lipophilic anions such as bromthymolblue, bromcresolpurple, and 8-anilino-1-napthalene sulphonate cause a pH-independent, 50% uncoupling in submitochondrial particles at concentrations of 3, 30 and 30 muM, respectively. The passive interaction of bromthymolblue and bromcresolpurple appears as a pH-dependent distribution between two pHases. ATP causes a pH-independent slight shift in the anion distribution, with negligible anion accumulation. 4. Addition of amines to energized submitochondrial particles results in two types of effects; uptake of amines and uncoupling. While in chloroplasts amine uptake and uncoupling are closely associated, this is not the case in submitochondrial particles. The uncoupling effect is observed only with lipophilic and not with hydrophilic amines, and the degree of uncoupling increases with the lipophilicity of the amines. The amine uptake, on the other hand, is accompanied by negligible uncoupling. 5. While the uptake of amines is dependent on the presence of non-permeant anions, such as Cl-, the uncoupling effect is independent of Cl-. Furthermore the amine uncoupling is markedly enhanced by lipophilic anions. 6. The view is discussed that the uncoupling effect of lipophilic anions and lipophilic amines in submitochondrial particles is due to a catalytic energy dissipation rather than to a stoichiometry energy utilization. The molecular mechanism of uncoupling presumably involves a cycling of charges after a perturbation of the membrane structure."}
{"id": "PMID:2478", "title": "Oral antipyretic therapy: evaluation of benorylate, an ester of acetylsalicylic acid and paracetamol.", "content": "The capacity of benorylate, an ester of acetylsalicylic acid and paracetamol, to reduce fever in children was compared with that of the components as such or as a combination. The series of cases studied consisted of 66 patients between the ages of 4 months and 12 years with rectal temperatures above 38.5 degrees C. Temperatures were recorded at 15 and 20 min and 1, 2, 4 and 6 hrs after the administration of the drug. The antipyretic effect of combined acetylsalicylic acid (11 mg/kg) and paracetamol (14 mg/kg) was superior to the effect of benorylate with a dose of 25 mg/kg and even of 50 mg/kg as well as better than the effect of either drug alone. Acetylsalicylic acid (10 mg/kg) and paracetamol (12.5 mg/kg) alone produced a significantly greater antipyretic effect than benorylate with a dose of 25 mg/kg. Given in a dose of 35--40 mg/kg, benorylate seems to have a significant antipyretic effect. However, this effect is clearly smaller than that of either of its components, acetylsalicylic acid or paracetamol. Therefore benorylate is probably not suitable to be used as a general antipyretic agent in children.", "contents": "Oral antipyretic therapy: evaluation of benorylate, an ester of acetylsalicylic acid and paracetamol. The capacity of benorylate, an ester of acetylsalicylic acid and paracetamol, to reduce fever in children was compared with that of the components as such or as a combination. The series of cases studied consisted of 66 patients between the ages of 4 months and 12 years with rectal temperatures above 38.5 degrees C. Temperatures were recorded at 15 and 20 min and 1, 2, 4 and 6 hrs after the administration of the drug. The antipyretic effect of combined acetylsalicylic acid (11 mg/kg) and paracetamol (14 mg/kg) was superior to the effect of benorylate with a dose of 25 mg/kg and even of 50 mg/kg as well as better than the effect of either drug alone. Acetylsalicylic acid (10 mg/kg) and paracetamol (12.5 mg/kg) alone produced a significantly greater antipyretic effect than benorylate with a dose of 25 mg/kg. Given in a dose of 35--40 mg/kg, benorylate seems to have a significant antipyretic effect. However, this effect is clearly smaller than that of either of its components, acetylsalicylic acid or paracetamol. Therefore benorylate is probably not suitable to be used as a general antipyretic agent in children."}
{"id": "PMID:2479", "title": "Effect of ischemic anoxia on electrical and mechanical activity of the totally isolated porcine stomach.", "content": "Electrical and mechanical activity were recorded from totally isolated whole porcine stomachs perfused with homologous blood. Stagnant, complete ischemia was then produced by closing the gastric artery and vein for various periods of time up to 3 h. After a given period of ischemia, blood was recirculated for 10 min and then pentagastrin was injected into the gastric artery. The vagus nerve was also electrically stimulated at various stages of anoxia and recirculation. After up to 90 min of ischemia, stomachs were able to demonstrate electrical control activity of low frequency after 10 min of blood recirculation. After injection of pentagastrin, electrical control activity rapidly became normal. When ischemia lasted 120 min or longer, recirculation of blood did not induce reappearance of electrical control activity, but pentagastrin injection produced a normal response. After ischemia of 240 min duration or longer, recirculation and pentagastrin had no effect. In previously ischemic stomachs the response to vagal stimulation occurred only in the stomachs responding to pentagastrin.", "contents": "Effect of ischemic anoxia on electrical and mechanical activity of the totally isolated porcine stomach. Electrical and mechanical activity were recorded from totally isolated whole porcine stomachs perfused with homologous blood. Stagnant, complete ischemia was then produced by closing the gastric artery and vein for various periods of time up to 3 h. After a given period of ischemia, blood was recirculated for 10 min and then pentagastrin was injected into the gastric artery. The vagus nerve was also electrically stimulated at various stages of anoxia and recirculation. After up to 90 min of ischemia, stomachs were able to demonstrate electrical control activity of low frequency after 10 min of blood recirculation. After injection of pentagastrin, electrical control activity rapidly became normal. When ischemia lasted 120 min or longer, recirculation of blood did not induce reappearance of electrical control activity, but pentagastrin injection produced a normal response. After ischemia of 240 min duration or longer, recirculation and pentagastrin had no effect. In previously ischemic stomachs the response to vagal stimulation occurred only in the stomachs responding to pentagastrin."}
{"id": "PMID:2480", "title": "Combined azaperone and metomidate anaesthesia in liver transplantation in the pig.", "content": "Combined azaperone and metomidate anaesthesia has been used in 86 surgical procedures on 84 piglets, either as such or deepened and prolonged. 51 animals were sacrificed at the end of the procedure as planned before. The anesthesia allowed the performance of various short and long operations. Out of the 33 remaining pigs, submitted to 35 operations, 4 died during the procedure of a technical fault; 2 did not recover from a deep hypothermia (below 10 degrees C); 1 died from the hepatic coma induced through the operative procedure. The other 26 awoke and recovered spontaneous breathing within 1-4 h following the type of anaesthesia and operating procedure they had submitted, which dured from 15 to 330 min.", "contents": "Combined azaperone and metomidate anaesthesia in liver transplantation in the pig. Combined azaperone and metomidate anaesthesia has been used in 86 surgical procedures on 84 piglets, either as such or deepened and prolonged. 51 animals were sacrificed at the end of the procedure as planned before. The anesthesia allowed the performance of various short and long operations. Out of the 33 remaining pigs, submitted to 35 operations, 4 died during the procedure of a technical fault; 2 did not recover from a deep hypothermia (below 10 degrees C); 1 died from the hepatic coma induced through the operative procedure. The other 26 awoke and recovered spontaneous breathing within 1-4 h following the type of anaesthesia and operating procedure they had submitted, which dured from 15 to 330 min."}
{"id": "PMID:2481", "title": "Cardiovascular and beta-adrenergic blocking effects of timolol.", "content": "The haemodynamic effects of timolol and its inhibiting action on the cardiovascular and bronchial effects of isoproterenol have been studied. Splanchnic nerve activity was recorded. The antiarrhythmic action of timolol was studied on guinea pig isolated atria, using arrhythmias induced by epinephrine, ouabain or coronary ligation in the dog. Timolol is a very potent beta-adrenoceptor blocking agent, without specificity on beta1- or beta2-receptors. No intrinsic beta-stimulating or depressant effects were found. Timolol reduced splanchnic discharges. The antiarrhythmic effect of timolol was limited to epinephrine-induced arrhythmias.", "contents": "Cardiovascular and beta-adrenergic blocking effects of timolol. The haemodynamic effects of timolol and its inhibiting action on the cardiovascular and bronchial effects of isoproterenol have been studied. Splanchnic nerve activity was recorded. The antiarrhythmic action of timolol was studied on guinea pig isolated atria, using arrhythmias induced by epinephrine, ouabain or coronary ligation in the dog. Timolol is a very potent beta-adrenoceptor blocking agent, without specificity on beta1- or beta2-receptors. No intrinsic beta-stimulating or depressant effects were found. Timolol reduced splanchnic discharges. The antiarrhythmic effect of timolol was limited to epinephrine-induced arrhythmias."}
{"id": "PMID:2482", "title": "Effects on rectal temperature in rats of gamma-aminobutyric acid; possible mediation through putative transmitters.", "content": "The rectal temperature of male rats was measured in a thermoneutral environment (25 degrees C) and at ambient temperatures of 15 and 35 degrees C. Unless otherwise specified all drugs were administered intracerebroventricularly (i.c.v.) and all results are reported for the thermoneutral environment. Exposure to 15 degrees C did not affect the rectal temperature but exposure to 35 degrees C produced hyperthermia. At 15 and 25 degrees C, 20 mug GABA produced hyperthermia which was longer lasting at the former ambient temperature. GABA (20 mug) prevented the hyperthermic effect of exposure to 35 degrees C and produced hypothermia in animals maintained at this temperature for 1 hr. A low dose (1 mug) of NA produced hyperthermia and a higher dose (mug) hypothermia. In rats pretreated with sodium salicylate (i.p.), 20 mug GABA and 1 mug NA produced hypothermia instead of hyperthermia, suggesting the release of PGE in mediating hyperthermia. The hypothermic effect of 10 mug NA and of GABA observed at 35 degrees C was blocked by phentolamine, an indication of the possibility of alpha-adrenoceptor mediation.", "contents": "Effects on rectal temperature in rats of gamma-aminobutyric acid; possible mediation through putative transmitters. The rectal temperature of male rats was measured in a thermoneutral environment (25 degrees C) and at ambient temperatures of 15 and 35 degrees C. Unless otherwise specified all drugs were administered intracerebroventricularly (i.c.v.) and all results are reported for the thermoneutral environment. Exposure to 15 degrees C did not affect the rectal temperature but exposure to 35 degrees C produced hyperthermia. At 15 and 25 degrees C, 20 mug GABA produced hyperthermia which was longer lasting at the former ambient temperature. GABA (20 mug) prevented the hyperthermic effect of exposure to 35 degrees C and produced hypothermia in animals maintained at this temperature for 1 hr. A low dose (1 mug) of NA produced hyperthermia and a higher dose (mug) hypothermia. In rats pretreated with sodium salicylate (i.p.), 20 mug GABA and 1 mug NA produced hypothermia instead of hyperthermia, suggesting the release of PGE in mediating hyperthermia. The hypothermic effect of 10 mug NA and of GABA observed at 35 degrees C was blocked by phentolamine, an indication of the possibility of alpha-adrenoceptor mediation."}
{"id": "PMID:2483", "title": "Analysis of cardiac chronotropic responses to diazepam and bromazepam in conscious trained dogs.", "content": "In conscious trained dogs, administration of bromazepam (0.3 mg/kg p.o.) or diazepam (0.3 and 1.0 mg/kg p.o.) had no influence on heart rate. A higher dose (10 mg/kg p.o.) of two benzodiazepines elicited a positive chronotropic effect which was rapid in onset and of long duration. The beta-adrenoceptor blocking agent practolol (2.5 mg/kg i.v.) did not revert heart rate after the benzodiazepines to the same level as in controls, indicating that the tachycardia was not produced by an increase in sympathetic outflow to the heart. For diazepam, a sympathetic--parasympathetic interaction cannot be excluded. However, diazepam and bromazepam significantly reduced the tachycardia which is normally observed after administration of methylatropine (0.5 mg/kg i.v.) alone or in combination with practolol. In anaesthetized dogs, bromazepam failed to modify the heart rate responses to electrical stimulation of cardiac vagal or sympathetic nerves, excluding an action on this compound on ganglionic transmission and cardiac cholinoceptors and adrenoceptors. It is concluded that high doses of diazepam and bromazepam influence the heart rate of conscious dogs in a biphasic way. Firstly, they cause a central reduction of vagal tone to the heart resulting in tachycardia. Secondly, the two drugs decrease the cardiac pacemaker rate directly. Since the overall effect is tachycardia, the central action is more pronounced.", "contents": "Analysis of cardiac chronotropic responses to diazepam and bromazepam in conscious trained dogs. In conscious trained dogs, administration of bromazepam (0.3 mg/kg p.o.) or diazepam (0.3 and 1.0 mg/kg p.o.) had no influence on heart rate. A higher dose (10 mg/kg p.o.) of two benzodiazepines elicited a positive chronotropic effect which was rapid in onset and of long duration. The beta-adrenoceptor blocking agent practolol (2.5 mg/kg i.v.) did not revert heart rate after the benzodiazepines to the same level as in controls, indicating that the tachycardia was not produced by an increase in sympathetic outflow to the heart. For diazepam, a sympathetic--parasympathetic interaction cannot be excluded. However, diazepam and bromazepam significantly reduced the tachycardia which is normally observed after administration of methylatropine (0.5 mg/kg i.v.) alone or in combination with practolol. In anaesthetized dogs, bromazepam failed to modify the heart rate responses to electrical stimulation of cardiac vagal or sympathetic nerves, excluding an action on this compound on ganglionic transmission and cardiac cholinoceptors and adrenoceptors. It is concluded that high doses of diazepam and bromazepam influence the heart rate of conscious dogs in a biphasic way. Firstly, they cause a central reduction of vagal tone to the heart resulting in tachycardia. Secondly, the two drugs decrease the cardiac pacemaker rate directly. Since the overall effect is tachycardia, the central action is more pronounced."}
{"id": "PMID:2484", "title": "The amphetamine-induced inhibition of dopamine biosynthesis in rat striatum.", "content": "The dopamine biosynthetic machinery of intact synaptosomes of rat striatum showed a 5-fold increase in development from 3-day-old neonates to adults, and it was fully developed between 2-3 weeks after birth. Concurring with this development was the appearance 2 weeks after birth of a regulatory mechanism(s) through which amphetamine in vivo induced an inhibition of dopamine biosynthesis. The inhibition was not appreciably reversed when haloperidol, in addition to amphetamine, was administered.", "contents": "The amphetamine-induced inhibition of dopamine biosynthesis in rat striatum. The dopamine biosynthetic machinery of intact synaptosomes of rat striatum showed a 5-fold increase in development from 3-day-old neonates to adults, and it was fully developed between 2-3 weeks after birth. Concurring with this development was the appearance 2 weeks after birth of a regulatory mechanism(s) through which amphetamine in vivo induced an inhibition of dopamine biosynthesis. The inhibition was not appreciably reversed when haloperidol, in addition to amphetamine, was administered."}
{"id": "PMID:2485", "title": "Toxicological aspects of dimethyl-ether.", "content": "The authors report the results of a series of investigations on the toxic effects produced in mice and rabbits by inhalation of Dimethyl-ether. Median lethal concentration (LC50) and Median lethal time (LT50) were determined in the mouse. Also the effects of DME inhalation on some physiological parameters (blood pressure, heart rate, blood gas and pH data) were evaluated in the rabbit.", "contents": "Toxicological aspects of dimethyl-ether. The authors report the results of a series of investigations on the toxic effects produced in mice and rabbits by inhalation of Dimethyl-ether. Median lethal concentration (LC50) and Median lethal time (LT50) were determined in the mouse. Also the effects of DME inhalation on some physiological parameters (blood pressure, heart rate, blood gas and pH data) were evaluated in the rabbit."}
{"id": "PMID:2489", "title": "[Gastric irrigation and secretion in the ligatured or fistuled pylorus rat upon influence of intra-duodenal olive oil (author's transl)].", "content": "Pylorus ligature hides the inhibitory effects of endogenous cholecystokinine-pancreozyme (CCK-PZ) on gastric mucosal secretion and irrigation, whereas the juice collected through transduodenal pyloric fistula makes this phenomenon obvious. It appears that the pyloric fistula encourages inhibition of gastrinic secretion, so that the CCK-PZ can achieve its effects.", "contents": "[Gastric irrigation and secretion in the ligatured or fistuled pylorus rat upon influence of intra-duodenal olive oil (author's transl)]. Pylorus ligature hides the inhibitory effects of endogenous cholecystokinine-pancreozyme (CCK-PZ) on gastric mucosal secretion and irrigation, whereas the juice collected through transduodenal pyloric fistula makes this phenomenon obvious. It appears that the pyloric fistula encourages inhibition of gastrinic secretion, so that the CCK-PZ can achieve its effects."}
{"id": "PMID:2490", "title": "Properties of glutamine aminohydrolases in subcellular fractions of liver of tumour bearing mice.", "content": "Glutamine aminohydrolase is found to be present in microsomal and soluble supernatant in liver of EAC-bearing mice. Enzymes obtained from these two sources were characterized and found to behave differently from the mitochondrial glutaminase of both normal and tumour-bearing mice.", "contents": "Properties of glutamine aminohydrolases in subcellular fractions of liver of tumour bearing mice. Glutamine aminohydrolase is found to be present in microsomal and soluble supernatant in liver of EAC-bearing mice. Enzymes obtained from these two sources were characterized and found to behave differently from the mitochondrial glutaminase of both normal and tumour-bearing mice."}
{"id": "PMID:2494", "title": "[Ability of adrenergic nerves to accumulate exogenous noradrenaline under some pharmacological influences].", "content": "By employing spectrofluorometry and quantitative fluorescent histochemistry the norepinephrine (NE) content in the tissue and in the adrenergic nerves of Vas deferens of the rat after depletion of the transmitter's reserves with tyramine and their subsequent replenishment through incubation of the tissue with exogenous NE was measured. The object of investigations was also the influence of antidepressants (phthoracizine and imipramine) and of the cholinolytic spasmolytin (diphacyl) on processes of the NE accumulation. Phthoracizine, impramine and spasmolytin were found to capable of inhibiting accumulation of the exogenous NE in the tissue and in the adrenergic nerves of Vas deferens, provided the mediator is present in the extraneuronal medium in a concentration of 0.5 gamma/ml. When the neurotransmitter was introduced into the medium in higher concentrations (10 gamma/ml) the antidepressents and cholinolytic did not produce the said effect. A correlation of spectrofluorometric and quantitative fluorescent-histochemical findings was observed in cases when the tissue contained less than 50% (i.e. less than 9 gamma/ml) of the total NE reserves.", "contents": "[Ability of adrenergic nerves to accumulate exogenous noradrenaline under some pharmacological influences]. By employing spectrofluorometry and quantitative fluorescent histochemistry the norepinephrine (NE) content in the tissue and in the adrenergic nerves of Vas deferens of the rat after depletion of the transmitter's reserves with tyramine and their subsequent replenishment through incubation of the tissue with exogenous NE was measured. The object of investigations was also the influence of antidepressants (phthoracizine and imipramine) and of the cholinolytic spasmolytin (diphacyl) on processes of the NE accumulation. Phthoracizine, impramine and spasmolytin were found to capable of inhibiting accumulation of the exogenous NE in the tissue and in the adrenergic nerves of Vas deferens, provided the mediator is present in the extraneuronal medium in a concentration of 0.5 gamma/ml. When the neurotransmitter was introduced into the medium in higher concentrations (10 gamma/ml) the antidepressents and cholinolytic did not produce the said effect. A correlation of spectrofluorometric and quantitative fluorescent-histochemical findings was observed in cases when the tissue contained less than 50% (i.e. less than 9 gamma/ml) of the total NE reserves."}
{"id": "PMID:2506", "title": "[Possible participation of potassium ions in the regulation of local cerebral blood flow].", "content": "The microinjections of mock spinal fluid with various potassium concentrations into the cat and monkey brain tissue were made in acute and chronic experiments. The vascular reactions as studied with the microphotography and H-clearance method were found to be linearly related to the potassium concentrations within the range of 0--12 mEq/1, being constrictory below 5 mEq/1 and dilatory above that. An interaction between MSF potassium and pH seems to be weak if any, since the slope of the potassium vascular activity diagram remains unchanged within 6.8--7.8 pH change. The data obtained suggest that potassium ions take part in rCBF control since potassium is known to escape from stimulated nerve cells and thus substantially increase an extracellular potassium concentration.", "contents": "[Possible participation of potassium ions in the regulation of local cerebral blood flow]. The microinjections of mock spinal fluid with various potassium concentrations into the cat and monkey brain tissue were made in acute and chronic experiments. The vascular reactions as studied with the microphotography and H-clearance method were found to be linearly related to the potassium concentrations within the range of 0--12 mEq/1, being constrictory below 5 mEq/1 and dilatory above that. An interaction between MSF potassium and pH seems to be weak if any, since the slope of the potassium vascular activity diagram remains unchanged within 6.8--7.8 pH change. The data obtained suggest that potassium ions take part in rCBF control since potassium is known to escape from stimulated nerve cells and thus substantially increase an extracellular potassium concentration."}
{"id": "PMID:2509", "title": "The alternate complement pathway in inflammatory bowel disease. Quantitation of the C3 proactivator (factor B) protein.", "content": "A component of the complement system's alternate pathway was investigated in ulcerative colitis and Crohn's disease. The mean C3PA (Factor B) titer in normals was 74 +/- 15%; in ulcerative colitis, 92 +/- 18%; and in Crohn's disease, 119+/- 24%. Significance was at the P less than 0.001 level when the mean values for the ulcerative colitis and the Crohn's disease groups were compared to normal subjects. Titers did not change significantly with exacerbation or amelioration of the diseases or when patient groups were analyzed according to the mode of treatment received.", "contents": "The alternate complement pathway in inflammatory bowel disease. Quantitation of the C3 proactivator (factor B) protein. A component of the complement system's alternate pathway was investigated in ulcerative colitis and Crohn's disease. The mean C3PA (Factor B) titer in normals was 74 +/- 15%; in ulcerative colitis, 92 +/- 18%; and in Crohn's disease, 119+/- 24%. Significance was at the P less than 0.001 level when the mean values for the ulcerative colitis and the Crohn's disease groups were compared to normal subjects. Titers did not change significantly with exacerbation or amelioration of the diseases or when patient groups were analyzed according to the mode of treatment received."}
{"id": "PMID:2510", "title": "Measurement of gastric functions during digestion of ordinary solid meals in man.", "content": "A method of measuring gastric secretions and emptying rates after ingestion of an ordinary (solid-liquid) meal has been developed and validated. The technique quantifies movements of volume across the pylorus using constant duodenal perfusion with a nonabsorbable marker, polyethylene glycol (PEG), which, in turn, quantifies emptying into the duodenum of another marker, [14C]PEG, incorporated in the meal. Acid and pepsin outputs can be determined without manipulation of the intragastric pH. Employing this method, we have simultaneously quantified acid, pepsin, and total secretory outputs; rates of gastric emptying of meal and secretions; and serum gastrin levels during digestion. These data characterize physiological responses to ordinary food in health.", "contents": "Measurement of gastric functions during digestion of ordinary solid meals in man. A method of measuring gastric secretions and emptying rates after ingestion of an ordinary (solid-liquid) meal has been developed and validated. The technique quantifies movements of volume across the pylorus using constant duodenal perfusion with a nonabsorbable marker, polyethylene glycol (PEG), which, in turn, quantifies emptying into the duodenum of another marker, [14C]PEG, incorporated in the meal. Acid and pepsin outputs can be determined without manipulation of the intragastric pH. Employing this method, we have simultaneously quantified acid, pepsin, and total secretory outputs; rates of gastric emptying of meal and secretions; and serum gastrin levels during digestion. These data characterize physiological responses to ordinary food in health."}
{"id": "PMID:2511", "title": "A dopamine receptor in esophageal smooth muscle of the opossum.", "content": "We examined the possibility that dopamine may play a role in nerve-mediated \"off\" responses of esophageal body (EB) and relaxations of lower esophageal spincter (LES) smooth muscle. The effects of dopamine, epinine, and dopamine antagonists on EB and LES smooth muscle were studied on these responses. Dopamine and epinine caused a dose-related fall in basal LES muscle tension and in amplitude of EB muscle \"off\" responses. Threshold dose for both was about 10(-7) M, and maximal dose was about 10(-4) M. At high concentrations, they also caused repetitive transient contractions of both LES and EB muscle after the period of inhibition. These effects were antagonized by haloperidol, 10(-5) M, and bulbocapnine, 10(-5) M, but were not influenced by propranolol, 10(-5) M, nor by phenoxybenzamine, 10(-5) M. Neither haloperidol nor bulbocapnine influenced responses to electrical field stimulation. Tetrodotoxin 10(-7) M abolished the responses to electrical field stimulation but did not antagonize the effects of dopamine and epinine. EB and LES smooth muscle contain a dopamine receptor. It is unlikely that dopamine is involved in responses to electrical field stimulation.", "contents": "A dopamine receptor in esophageal smooth muscle of the opossum. We examined the possibility that dopamine may play a role in nerve-mediated \"off\" responses of esophageal body (EB) and relaxations of lower esophageal spincter (LES) smooth muscle. The effects of dopamine, epinine, and dopamine antagonists on EB and LES smooth muscle were studied on these responses. Dopamine and epinine caused a dose-related fall in basal LES muscle tension and in amplitude of EB muscle \"off\" responses. Threshold dose for both was about 10(-7) M, and maximal dose was about 10(-4) M. At high concentrations, they also caused repetitive transient contractions of both LES and EB muscle after the period of inhibition. These effects were antagonized by haloperidol, 10(-5) M, and bulbocapnine, 10(-5) M, but were not influenced by propranolol, 10(-5) M, nor by phenoxybenzamine, 10(-5) M. Neither haloperidol nor bulbocapnine influenced responses to electrical field stimulation. Tetrodotoxin 10(-7) M abolished the responses to electrical field stimulation but did not antagonize the effects of dopamine and epinine. EB and LES smooth muscle contain a dopamine receptor. It is unlikely that dopamine is involved in responses to electrical field stimulation."}
{"id": "PMID:2513", "title": "[Continuous subcutaneous pH monitoring in newborns with abnormal metabolism (author's transl)].", "content": "In newborns with postpartum acidosis the subcutaneous interstitiel space pH was monitored continuously with the special electrode of Stamm and Moeller. This was compared with intermittent determinations of the pH in the capillary blood from the heel of the infant. The severity of the metabolic disturbance can be recognized in all test cases with both methods. The correction of the acidosis develops in a concordant manner, in a concordant magnitude and at a largely synchronous rate. The observations show that it is possible to monitor the postpartum adaptation phase by continuous pH monitoring in the interstitial space of the subcutaneous tissue and to observe the efficiency of the treatment of acidosis, administration of oxygen, or a buffer infusion.", "contents": "[Continuous subcutaneous pH monitoring in newborns with abnormal metabolism (author's transl)]. In newborns with postpartum acidosis the subcutaneous interstitiel space pH was monitored continuously with the special electrode of Stamm and Moeller. This was compared with intermittent determinations of the pH in the capillary blood from the heel of the infant. The severity of the metabolic disturbance can be recognized in all test cases with both methods. The correction of the acidosis develops in a concordant manner, in a concordant magnitude and at a largely synchronous rate. The observations show that it is possible to monitor the postpartum adaptation phase by continuous pH monitoring in the interstitial space of the subcutaneous tissue and to observe the efficiency of the treatment of acidosis, administration of oxygen, or a buffer infusion."}
{"id": "PMID:2514", "title": "[The significance of gestational age in evaluating the antepartal cardiotokogram (author's transl)].", "content": "The influence of gestational age on the probable meaning of features in the antepartal CTG which are not clearly pathological was investigated in 232 births in 1973/74. The umbilical artery pH was significantly lower among premature infants exhibiting abnormal, than among those exhibiting normal CTG patterns. No similar difference was found in term or overdue births. The clinical diagnosis of neonatal condition using the Apgar scheme confirmed biochemical findings: The frequency of depressed babies is in turn clearly higher in cases with abnormal antepartal CTG patterns. It is assumed that the reason for this is the higher sensitivity of premature babies to haemodynamic disturbances. Thus, it follows that premature babies exhibiting antepartal patterns which are not completely normal require close observation.", "contents": "[The significance of gestational age in evaluating the antepartal cardiotokogram (author's transl)]. The influence of gestational age on the probable meaning of features in the antepartal CTG which are not clearly pathological was investigated in 232 births in 1973/74. The umbilical artery pH was significantly lower among premature infants exhibiting abnormal, than among those exhibiting normal CTG patterns. No similar difference was found in term or overdue births. The clinical diagnosis of neonatal condition using the Apgar scheme confirmed biochemical findings: The frequency of depressed babies is in turn clearly higher in cases with abnormal antepartal CTG patterns. It is assumed that the reason for this is the higher sensitivity of premature babies to haemodynamic disturbances. Thus, it follows that premature babies exhibiting antepartal patterns which are not completely normal require close observation."}
{"id": "PMID:2523", "title": "Characteristics of lipopolysaccharides of Salmonella typhi isolated from carriers and patients suffering from typhoid fever.", "content": "Lipopolysaccharides (LPS) of Salmonella typhi strains, isolated from carriers and patients suffering from typhoid fever, were characterised according to their biochemical properties, morphological structure and degree of aggregation of complexes. All preparations of LPS, regardless of their origin, were morphologically heterogeneous. Free electrophoresis and immunoelectrophoresis demonstrated that LPS preparations were composed of components possessing different mobilities in electric fields. LPS of bacterial strains isolated from both carriers and patients, split upon reaction in immunoelectrophoresis with specific antiserum 73, rabbit antiserum to Salmonella typhi Vi Bhatnagar and 0-901 split into anodic and cathodic fractions. The anodic fraction reacted similarly as Vi antigen. LPS from Salmonella typhi Ty-2 yielded only the cathodic fraction, typical for O antigen. LPS from strains which were passaged twice in nutritional medium possessed identical properties as LPS from fresh cultures of Salmonella typhi. Electron microscopy revealed that LPS appears as long bands, rods, ellipsoid forms and amorphous material. Contrary to amorphous material, the bands, rods and ellipsoid forms possessed three-layer structure.", "contents": "Characteristics of lipopolysaccharides of Salmonella typhi isolated from carriers and patients suffering from typhoid fever. Lipopolysaccharides (LPS) of Salmonella typhi strains, isolated from carriers and patients suffering from typhoid fever, were characterised according to their biochemical properties, morphological structure and degree of aggregation of complexes. All preparations of LPS, regardless of their origin, were morphologically heterogeneous. Free electrophoresis and immunoelectrophoresis demonstrated that LPS preparations were composed of components possessing different mobilities in electric fields. LPS of bacterial strains isolated from both carriers and patients, split upon reaction in immunoelectrophoresis with specific antiserum 73, rabbit antiserum to Salmonella typhi Vi Bhatnagar and 0-901 split into anodic and cathodic fractions. The anodic fraction reacted similarly as Vi antigen. LPS from Salmonella typhi Ty-2 yielded only the cathodic fraction, typical for O antigen. LPS from strains which were passaged twice in nutritional medium possessed identical properties as LPS from fresh cultures of Salmonella typhi. Electron microscopy revealed that LPS appears as long bands, rods, ellipsoid forms and amorphous material. Contrary to amorphous material, the bands, rods and ellipsoid forms possessed three-layer structure."}
{"id": "PMID:2524", "title": "Reduction of blood platelet monoamine oxidase activity in schizophrenic patients on phenothiazines.", "content": "A newly developed assay for monoamine oxidase (MAO) activity in blood platelets (serotonin used as substrate) was applied for the measurement of the enzyme activity in 76 schizophrenic patients. No significant reduction was found in the blood platelet MAO activity in a group of 33 untreated schizophrenic patients, as compared to that in the normal controls. Male patients revealed to have lower enzyme activity than females in the schizophrenic group, as we described previously in the normal subjects. Treatment with phenothiazines caused significant reduction of blood platelet MAO activity, while platelet serotonin content and platelet count appeared to be not affected by the drug treatment. The authors suggest that blood platelet MAO activity may be related to hormonal factors but not to psychiatric diagnosis of schizophrenia or constitution liable to schizophrenic illnesses.", "contents": "Reduction of blood platelet monoamine oxidase activity in schizophrenic patients on phenothiazines. A newly developed assay for monoamine oxidase (MAO) activity in blood platelets (serotonin used as substrate) was applied for the measurement of the enzyme activity in 76 schizophrenic patients. No significant reduction was found in the blood platelet MAO activity in a group of 33 untreated schizophrenic patients, as compared to that in the normal controls. Male patients revealed to have lower enzyme activity than females in the schizophrenic group, as we described previously in the normal subjects. Treatment with phenothiazines caused significant reduction of blood platelet MAO activity, while platelet serotonin content and platelet count appeared to be not affected by the drug treatment. The authors suggest that blood platelet MAO activity may be related to hormonal factors but not to psychiatric diagnosis of schizophrenia or constitution liable to schizophrenic illnesses."}
{"id": "PMID:2527", "title": "[Inflammatory cerebro-vascular disease: angiographic findings and distribution patterns (author's transl)].", "content": "Although cerebral angiography should be approached with caution in the diagnosis of inflammatory cerebro-vascular disease there are some characteristic angiographic findings which may be helpful for classification and differential diagnosis. The proximal cerebral arteries are favourably affected by basal meningitis and thrombangiitis obliterans with resulting stenoses and occlusions. Whereas those inflammations originating from neighbouring skull structures mostly involve the intracavernous parts of the carotid artery, the tuberculous and mycotic arteritis prefer the supraclinoid carotid siphon. Peripheral vascular changes are found in luetic endangiitis, necrotizing and toxic angiitis and in collagenoses. Simultaneous involvement of the temporal arteries is of great diagnostic importance demonstrating the systemic character of the inflammatory process; in Horton's arteritis it can be a pathognomonic finding. Infectious endocarditis, some mycoses and malaria may lead to embolic occlusion of cerebral vessels. Mycotic aneurysms mostly have a broad base or a fusiform shape and do not prefer the localizations of congenital aneurysms. Angiographically, abscesses, tuberculomas and viral encephalitis may result in circumscribed hypervascularized areas. The characteristic angiographic findings are exemplified and discussed on the basis of 8 cases of inflammatory cerebro-vascular disease (tuberculosis, pneumococcal and unspecific bacterial meningitis, syphilis, mycosis, Takayasu-syndrome, panarteritis nodosa, temporal arteritis).", "contents": "[Inflammatory cerebro-vascular disease: angiographic findings and distribution patterns (author's transl)]. Although cerebral angiography should be approached with caution in the diagnosis of inflammatory cerebro-vascular disease there are some characteristic angiographic findings which may be helpful for classification and differential diagnosis. The proximal cerebral arteries are favourably affected by basal meningitis and thrombangiitis obliterans with resulting stenoses and occlusions. Whereas those inflammations originating from neighbouring skull structures mostly involve the intracavernous parts of the carotid artery, the tuberculous and mycotic arteritis prefer the supraclinoid carotid siphon. Peripheral vascular changes are found in luetic endangiitis, necrotizing and toxic angiitis and in collagenoses. Simultaneous involvement of the temporal arteries is of great diagnostic importance demonstrating the systemic character of the inflammatory process; in Horton's arteritis it can be a pathognomonic finding. Infectious endocarditis, some mycoses and malaria may lead to embolic occlusion of cerebral vessels. Mycotic aneurysms mostly have a broad base or a fusiform shape and do not prefer the localizations of congenital aneurysms. Angiographically, abscesses, tuberculomas and viral encephalitis may result in circumscribed hypervascularized areas. The characteristic angiographic findings are exemplified and discussed on the basis of 8 cases of inflammatory cerebro-vascular disease (tuberculosis, pneumococcal and unspecific bacterial meningitis, syphilis, mycosis, Takayasu-syndrome, panarteritis nodosa, temporal arteritis)."}
{"id": "PMID:2528", "title": "Oxidative deamination of biogenic amines by intestinal amine oxidases: histamine is specifically inactivated by diamine oxidase.", "content": "The ability of the gut to inactivate various amines by oxidative deamination was tested with a 130-fold purified amine oxidase preparation from dog small intestine. Of 34 amines tested, putrescine, benzylamine, cadaverine, and serotonin were the most favourable substrates. Histamine was inactivated rapidly by this enzyme preparation, too. Histamine derivatives methylated at the imidazole nucleus were also deaminated, whereas Nalpha-methylhistamine was only a poor substrate and Nalpha, Nalpha-dimethylhistamine was not a substrate at all. Using a second procedure for the purification of amine oxidases from gut, the separation of a soluble monoamine oxidase from diamine oxidase was achieved by gel filtration on Sephadex G-200. The diamine oxidase deaminated putrescine (Km = 1.3 x 10(-4)M) and histamine (Km = 6.6 x 10(-5)M), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. The soluble monoamine oxidase inactivated serotonin (Km = 4.5 x 10(-4)M), but not histamine and putrescine and was inhibited by pargyline, but not by aminoguanidine. It was concluded that in dog small intestine (as well as in rabbit small intestine) only diamine oxidase was capable of inactivating histamine by oxidative deamination.", "contents": "Oxidative deamination of biogenic amines by intestinal amine oxidases: histamine is specifically inactivated by diamine oxidase. The ability of the gut to inactivate various amines by oxidative deamination was tested with a 130-fold purified amine oxidase preparation from dog small intestine. Of 34 amines tested, putrescine, benzylamine, cadaverine, and serotonin were the most favourable substrates. Histamine was inactivated rapidly by this enzyme preparation, too. Histamine derivatives methylated at the imidazole nucleus were also deaminated, whereas Nalpha-methylhistamine was only a poor substrate and Nalpha, Nalpha-dimethylhistamine was not a substrate at all. Using a second procedure for the purification of amine oxidases from gut, the separation of a soluble monoamine oxidase from diamine oxidase was achieved by gel filtration on Sephadex G-200. The diamine oxidase deaminated putrescine (Km = 1.3 x 10(-4)M) and histamine (Km = 6.6 x 10(-5)M), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. The soluble monoamine oxidase inactivated serotonin (Km = 4.5 x 10(-4)M), but not histamine and putrescine and was inhibited by pargyline, but not by aminoguanidine. It was concluded that in dog small intestine (as well as in rabbit small intestine) only diamine oxidase was capable of inactivating histamine by oxidative deamination."}
{"id": "PMID:2525", "title": "Comparative toxicology in vitreous humor and blood.", "content": "Drug and toxic substances were detected in blood and vitreous humor in fifty-six cases, in which causes of death were both from an overdose of the particular substances and from other unrelated causes. Five instances are reported in which two drug substances were detected in blood and vitreous humor from the same subject. Patients having long survival times, as well as those dying from unrelated causes, reveal drug values to approach unity, when the blood and vitreous concentrations are compared. The ratios reached at equilibrium probably depend on solubility of the drug in vitreous humor, lipid solubility and the percentage protein-bound in the blood. The vitreous humor provides another parameter of testing and may be useful in studies of survival time.", "contents": "Comparative toxicology in vitreous humor and blood. Drug and toxic substances were detected in blood and vitreous humor in fifty-six cases, in which causes of death were both from an overdose of the particular substances and from other unrelated causes. Five instances are reported in which two drug substances were detected in blood and vitreous humor from the same subject. Patients having long survival times, as well as those dying from unrelated causes, reveal drug values to approach unity, when the blood and vitreous concentrations are compared. The ratios reached at equilibrium probably depend on solubility of the drug in vitreous humor, lipid solubility and the percentage protein-bound in the blood. The vitreous humor provides another parameter of testing and may be useful in studies of survival time."}
{"id": "PMID:2529", "title": "Electrodecantation of serum proteins.", "content": "The sedimentation of albumin under the action of the electric and gravitational fields was determined as a function of time in discontinuous experiments in a rectangular cell, using serum with the albumin fraction stained blue. It was shown that even under the influence of strong electric fields, the upper boundary of the albumin layer fell no further than the mid-point of the cell. In continuous single-stage separation of gamma-globulin from other serum proteins, only about half the gamma-globulins can be obtained from the solution because it remains homogeneously distributed throughout the solution and is only free from albumin and other proteins in the upper half of the cell. In experiments with continuously operated triangular cells, the process was optimized to give gamma-globulin of 97.5% purity in a yield of 80%, at serum flow-through rates of up to 0.5 l/h in a block composed of 40 cells.", "contents": "Electrodecantation of serum proteins. The sedimentation of albumin under the action of the electric and gravitational fields was determined as a function of time in discontinuous experiments in a rectangular cell, using serum with the albumin fraction stained blue. It was shown that even under the influence of strong electric fields, the upper boundary of the albumin layer fell no further than the mid-point of the cell. In continuous single-stage separation of gamma-globulin from other serum proteins, only about half the gamma-globulins can be obtained from the solution because it remains homogeneously distributed throughout the solution and is only free from albumin and other proteins in the upper half of the cell. In experiments with continuously operated triangular cells, the process was optimized to give gamma-globulin of 97.5% purity in a yield of 80%, at serum flow-through rates of up to 0.5 l/h in a block composed of 40 cells."}
{"id": "PMID:2526", "title": "Recent studies on cytochrome P-450-linked functions in isolated rat liver cells.", "content": "In rat liver cells isolated by perfusion in the perfusion in the presence of collagenase, the major portion of cytochrome P-450 is present in the oxidized, nonsubstrate-bound, low spin state. Drug addition to a suspension of liver cells results in the rapid formation of the cytochrome P-450 (Fe3+)-substrate complex which in turn is followed by the appearance of other species with different spectral characteristics before steady state drug monooxygenation is achieved. Cytochrome P-450-linked metabolism of various tested drugs and carcinogenic polycyclic hydrocarbons by isolated rat liver cells is as fast, or faster, as with rat liver microsomes supplemented with a NADPH generating system. Both experimental models respond similarily to phenobarbital or 3-methylcholanthrene pretreatment of the animals and to various of the wellknown inhibitors of drug metabolism. Except with liver cells isolated from fasted, phenobarbital-treated rats, generation of cytosolic NADPH seems sufficient to support optimal drug metabolism even in the absence of added substrates of intermediary metabolism. In isolated liver cells oxidized drug metabolites undergo subsequent metabolic conversion, most often to form the corresponding glucuronides and sulphates. These are readily excreted, whereas non-conjugated products, e.g. free phenols, tend to accumulate intracellularly. Cellular glucuronide formation is strongly inhibited by ethanol-presumably due to an unfavorable effect of the increased NADH/NAD+ ratio on the synthesis of uridine-5'-diphosphoglucuronic acid (UDPGA). In contrast, low concentrations of ethanol have no, or only a slight stimulatory effect on the cytochrome P-450-linked step of drug metabolism and there are indications that the oxidation of low concentrations of ethanol is in fact stimulated by a facilitated reoxidation of cytosolic NADH occuring during drug monooxygenation.", "contents": "Recent studies on cytochrome P-450-linked functions in isolated rat liver cells. In rat liver cells isolated by perfusion in the perfusion in the presence of collagenase, the major portion of cytochrome P-450 is present in the oxidized, nonsubstrate-bound, low spin state. Drug addition to a suspension of liver cells results in the rapid formation of the cytochrome P-450 (Fe3+)-substrate complex which in turn is followed by the appearance of other species with different spectral characteristics before steady state drug monooxygenation is achieved. Cytochrome P-450-linked metabolism of various tested drugs and carcinogenic polycyclic hydrocarbons by isolated rat liver cells is as fast, or faster, as with rat liver microsomes supplemented with a NADPH generating system. Both experimental models respond similarily to phenobarbital or 3-methylcholanthrene pretreatment of the animals and to various of the wellknown inhibitors of drug metabolism. Except with liver cells isolated from fasted, phenobarbital-treated rats, generation of cytosolic NADPH seems sufficient to support optimal drug metabolism even in the absence of added substrates of intermediary metabolism. In isolated liver cells oxidized drug metabolites undergo subsequent metabolic conversion, most often to form the corresponding glucuronides and sulphates. These are readily excreted, whereas non-conjugated products, e.g. free phenols, tend to accumulate intracellularly. Cellular glucuronide formation is strongly inhibited by ethanol-presumably due to an unfavorable effect of the increased NADH/NAD+ ratio on the synthesis of uridine-5'-diphosphoglucuronic acid (UDPGA). In contrast, low concentrations of ethanol have no, or only a slight stimulatory effect on the cytochrome P-450-linked step of drug metabolism and there are indications that the oxidation of low concentrations of ethanol is in fact stimulated by a facilitated reoxidation of cytosolic NADH occuring during drug monooxygenation."}
{"id": "PMID:2530", "title": "D-glucose dehydrogenase from Bacillus megaterium M 1286: purification, properties and structure.", "content": "1) Glucose dehydrogenase from Bacillus megaterium has been purified to a specific activity of 550 U per mg protein. The homogeneity of the purified enzyme was demonstrated by gel electrophoresis and isoelectric focusing. 2) The amino acid composition has been determined. 3) The molecular weight of the native enzyme was found to be 116000 by gel permeation chromatography, in good agreement with the values of 120000 and 118000, which were ascertained electrophoretically according to the method of Hedrick and Smith and by density gradient centrifugation, respectively. 4) In the presence of 0.1% sodium dodecylsulfate and 8M urea, the enzyme dissociates into subunits with a molecular weight of 30000 as determined by dodecylsulfate gel electrophoresis. These values indicate that the native enzyme is composed of four polypeptide chains, each probably possessing one coenzyme binding site, which can be concluded from fluorescent titration of the NADH binding sites. 5) In polyacrylamide disc electrophoresis, samples of the purified enzyme exhibit three bands of activity, which present the native (tetrameric) form of glucose dehydrogenase and two monomeric forms (molecular weight 30000), arising under the conditions of pH and ionic strength of this method. 6) The enzyme shows a sharp pH optimum at pH 8.0 in Tris/HCl buffer, and a shift of the pH optimum to pH 9.0 in acetate/borate buffer. The limiting Michaelis constant at pH 9.0 for NAD is 4.5 mM and 47.5 mM for glucose. The dissociation constant for NAD is 0.69 mM. 7) D-Glucose dehydrogenase is highly specific for beta-D-glucose and is capable of using either NAD or NADP. The enzyme is insensitive to sulfhydryl group inhibitors, heavy metal ions and chelating agents.", "contents": "D-glucose dehydrogenase from Bacillus megaterium M 1286: purification, properties and structure. 1) Glucose dehydrogenase from Bacillus megaterium has been purified to a specific activity of 550 U per mg protein. The homogeneity of the purified enzyme was demonstrated by gel electrophoresis and isoelectric focusing. 2) The amino acid composition has been determined. 3) The molecular weight of the native enzyme was found to be 116000 by gel permeation chromatography, in good agreement with the values of 120000 and 118000, which were ascertained electrophoretically according to the method of Hedrick and Smith and by density gradient centrifugation, respectively. 4) In the presence of 0.1% sodium dodecylsulfate and 8M urea, the enzyme dissociates into subunits with a molecular weight of 30000 as determined by dodecylsulfate gel electrophoresis. These values indicate that the native enzyme is composed of four polypeptide chains, each probably possessing one coenzyme binding site, which can be concluded from fluorescent titration of the NADH binding sites. 5) In polyacrylamide disc electrophoresis, samples of the purified enzyme exhibit three bands of activity, which present the native (tetrameric) form of glucose dehydrogenase and two monomeric forms (molecular weight 30000), arising under the conditions of pH and ionic strength of this method. 6) The enzyme shows a sharp pH optimum at pH 8.0 in Tris/HCl buffer, and a shift of the pH optimum to pH 9.0 in acetate/borate buffer. The limiting Michaelis constant at pH 9.0 for NAD is 4.5 mM and 47.5 mM for glucose. The dissociation constant for NAD is 0.69 mM. 7) D-Glucose dehydrogenase is highly specific for beta-D-glucose and is capable of using either NAD or NADP. The enzyme is insensitive to sulfhydryl group inhibitors, heavy metal ions and chelating agents."}
{"id": "PMID:2532", "title": "[Enzyme induction in Streptomyces hydrogenans. V. Characterization of testosterone-17 beta-dehydrogenase and its induction by steroids].", "content": "Testosterone 17beta-dehydrogenase can be enriched from Streptomyces hydrogenans. The enzyme dehydrogenizes testosterone with Km=13muM and estradiol-17beta with Km=21muM to the corresponding 17-ketoderivatives. NAD forms NADH with Km=125muM. The enzyme is strongly inhibited by androstandione and 17alpha-methyltestosterone. The Ki for 17alpha-methyltestosterone is 18muM. The enzyme activity increases with increasing pH up to alkali-mediated denaturation at about pH 10. The optimum temperature is at 45 degrees C. If Streptomyces hydrogenans is cultivated in the absence of steroids, the specific activity of testosterone 17beta-dehydrogenase in the cytosol of the microorganisms amounts to 10 mU/mg protein, and increases up to 10-fold if the cells are cultivated in the presence of certain steroids. Testosterone, alpha-dihydrotestosterone, beta-dihydrotestosterone, estradiol-17beta, and 17alpha-methyltestosterone are very effective inducers. Thus, for the first time, the ability of estradiol-17beta to induce an enzyme synthesis in a microorganism is shown. The steroid-dependent induction is inhibited by testosterone acetate and rifamycin SV. Cyproterone, however, does not decrease the testosterone-dependent enzyme induction of testosterone 17beta-dehydrogenase.", "contents": "[Enzyme induction in Streptomyces hydrogenans. V. Characterization of testosterone-17 beta-dehydrogenase and its induction by steroids]. Testosterone 17beta-dehydrogenase can be enriched from Streptomyces hydrogenans. The enzyme dehydrogenizes testosterone with Km=13muM and estradiol-17beta with Km=21muM to the corresponding 17-ketoderivatives. NAD forms NADH with Km=125muM. The enzyme is strongly inhibited by androstandione and 17alpha-methyltestosterone. The Ki for 17alpha-methyltestosterone is 18muM. The enzyme activity increases with increasing pH up to alkali-mediated denaturation at about pH 10. The optimum temperature is at 45 degrees C. If Streptomyces hydrogenans is cultivated in the absence of steroids, the specific activity of testosterone 17beta-dehydrogenase in the cytosol of the microorganisms amounts to 10 mU/mg protein, and increases up to 10-fold if the cells are cultivated in the presence of certain steroids. Testosterone, alpha-dihydrotestosterone, beta-dihydrotestosterone, estradiol-17beta, and 17alpha-methyltestosterone are very effective inducers. Thus, for the first time, the ability of estradiol-17beta to induce an enzyme synthesis in a microorganism is shown. The steroid-dependent induction is inhibited by testosterone acetate and rifamycin SV. Cyproterone, however, does not decrease the testosterone-dependent enzyme induction of testosterone 17beta-dehydrogenase."}
{"id": "PMID:2533", "title": "Boar acrosin, II: Amino acid composition, amino terminal residue and molecular weight estimations by ultracentrifugation.", "content": "The molecular weight of boar acrosin in neutral solution was estimated to be 41000 +/- 1000 by high-speed sedimentation equilibrium analysis. This result is in good agreement with the value found earlier[1] by sodium dodecylsulfate polyacrylamide gel electrophoresis. The sedimentation coefficeint of acrosin obtained by active enzyme centrifugation of partly purified preparations is in accordance with the sedimentation coefficient of the pure preparation estimated by conventional sedimentation velocity analysis. The sedimentation coefficient of acrosin is considerably decreased in slightly acidic solution (pH 4), indicating that changes in the tertiary structure occur upon acidification. The amino acid composition of the acrosin preparation homogeneous by electrophoretic and chromatographic criteria and in sedimentation studies was determined. Valine was found as the unique N-terminal amino acid. However, in microheterogeneous forms of acrosin, alanine and methionine were also detected in end group analysis.", "contents": "Boar acrosin, II: Amino acid composition, amino terminal residue and molecular weight estimations by ultracentrifugation. The molecular weight of boar acrosin in neutral solution was estimated to be 41000 +/- 1000 by high-speed sedimentation equilibrium analysis. This result is in good agreement with the value found earlier[1] by sodium dodecylsulfate polyacrylamide gel electrophoresis. The sedimentation coefficeint of acrosin obtained by active enzyme centrifugation of partly purified preparations is in accordance with the sedimentation coefficient of the pure preparation estimated by conventional sedimentation velocity analysis. The sedimentation coefficient of acrosin is considerably decreased in slightly acidic solution (pH 4), indicating that changes in the tertiary structure occur upon acidification. The amino acid composition of the acrosin preparation homogeneous by electrophoretic and chromatographic criteria and in sedimentation studies was determined. Valine was found as the unique N-terminal amino acid. However, in microheterogeneous forms of acrosin, alanine and methionine were also detected in end group analysis."}
{"id": "PMID:2534", "title": "Characterization of protein kinases from Blepharisma intermedium.", "content": "Three protein kinases (EC 2.7.1.37) were detected in Blepharisma and partially purified. The enzymes were most active with histone as substrate protein. The stability of the bond between phosphate and protein acceptor showed the characteristics of seryl- or threonylphosphate. Protein kinase I was solubilized by ultrasonication or freezing and thawing, while the enzymes II and III were readily solubilized by mild homogenization. Protein II and III were noticeably activated by cAMP and cGMP, while protein kinase I was inhibited by cAMP. Associated with protein kinase II and III activity was the ability to bind labeled cAMP. The following molecular weights were determined: 90000 for enzyme I, 280000 for enzyme II, and 95000 for enzyme III. Various apparent Michaelis constants were estimated.", "contents": "Characterization of protein kinases from Blepharisma intermedium. Three protein kinases (EC 2.7.1.37) were detected in Blepharisma and partially purified. The enzymes were most active with histone as substrate protein. The stability of the bond between phosphate and protein acceptor showed the characteristics of seryl- or threonylphosphate. Protein kinase I was solubilized by ultrasonication or freezing and thawing, while the enzymes II and III were readily solubilized by mild homogenization. Protein II and III were noticeably activated by cAMP and cGMP, while protein kinase I was inhibited by cAMP. Associated with protein kinase II and III activity was the ability to bind labeled cAMP. The following molecular weights were determined: 90000 for enzyme I, 280000 for enzyme II, and 95000 for enzyme III. Various apparent Michaelis constants were estimated."}
{"id": "PMID:2535", "title": "[Solubilization and purification of a 3alpha-hydroxysteroid dehydrogenase in rat liver microsomes (author's transl)].", "content": "The microsomal 3-hydroxysteroid dehydrogenases were solubilized with lubrol, a non-ionic detergent. A 3alpha-hydroxysteroid dehydrogenase is purified about 100-fold by double affinity chromatography on 5alpha-dihydrotestosterone-Sepharose. This enzyme can use both NADH and NADPH as coenzymes.", "contents": "[Solubilization and purification of a 3alpha-hydroxysteroid dehydrogenase in rat liver microsomes (author's transl)]. The microsomal 3-hydroxysteroid dehydrogenases were solubilized with lubrol, a non-ionic detergent. A 3alpha-hydroxysteroid dehydrogenase is purified about 100-fold by double affinity chromatography on 5alpha-dihydrotestosterone-Sepharose. This enzyme can use both NADH and NADPH as coenzymes."}
{"id": "PMID:2549", "title": "The dissociation of insect embryos for cell culture.", "content": "Procedures and solutions were developed for dissociating embryos of Blattella germanica in preparation for primary cell culture. Trypsin solutions were maximally effective at 0.01% for germ bands but higher concentrations, 0.05 to 0.1% were needed for embryos in later stages.", "contents": "The dissociation of insect embryos for cell culture. Procedures and solutions were developed for dissociating embryos of Blattella germanica in preparation for primary cell culture. Trypsin solutions were maximally effective at 0.01% for germ bands but higher concentrations, 0.05 to 0.1% were needed for embryos in later stages."}
{"id": "PMID:2548", "title": "Effect of sodium butyrate on mammalian cells in culture: a review.", "content": "Sodium butyrate produces reversible changes in morphology, growth rate, and enzyme activities of several mammalian cell types in culture. Some of these changes are similar to those produced by agents which increase the intracellular level of adenosine 3',5'-cyclic monophosphate (cAMP) or by analogs of cAMP. Sodium butyrate increases the intracellular level of cAMP by about two fold in neuroblastoma cells; therefore, some of the effects of sodium butyrate on these cells may in part be mediated by cAMP. Sodium butyrate appears to have properties of a good chemotherapeutic agent for neuroblastoma tumors because the treatment of neuroblastoma cells in culture causes cell death and \"differentiation\"; however, it is either innocuous or produces reversible morphological and biochemical alterations in other cell types.", "contents": "Effect of sodium butyrate on mammalian cells in culture: a review. Sodium butyrate produces reversible changes in morphology, growth rate, and enzyme activities of several mammalian cell types in culture. Some of these changes are similar to those produced by agents which increase the intracellular level of adenosine 3',5'-cyclic monophosphate (cAMP) or by analogs of cAMP. Sodium butyrate increases the intracellular level of cAMP by about two fold in neuroblastoma cells; therefore, some of the effects of sodium butyrate on these cells may in part be mediated by cAMP. Sodium butyrate appears to have properties of a good chemotherapeutic agent for neuroblastoma tumors because the treatment of neuroblastoma cells in culture causes cell death and \"differentiation\"; however, it is either innocuous or produces reversible morphological and biochemical alterations in other cell types."}
{"id": "PMID:2550", "title": "On the nature of the presumed receptor for IgE on mast cells. III. Kinetics of the blocking of the PCA reaction by cell-free particulate preparations from rat peritoneal mast cells and effect of pH and calcium concentration on the reaction.", "content": "The 'binding' of IgE to particulate preparations derived from sonicated purified rat mast cells was measured by the blocking of PCA titrations of the supernatant solutions from incubations with such preparations. It was found that the PCA blocking reaction was inhibited by the addition of calcium ion to the incubations. The blocking reaction was strongly dependent on the pH of the incubations, being maximal at pH values lower than 5-0. The blocking reaction proceeded in a linear manner for at least 3 h provided that no more than 70 percent of the amount of IgE initially supplied had been removed by the particulate fraction. Only mast cell-derived preparations were capable of effecting PCA blocking.", "contents": "On the nature of the presumed receptor for IgE on mast cells. III. Kinetics of the blocking of the PCA reaction by cell-free particulate preparations from rat peritoneal mast cells and effect of pH and calcium concentration on the reaction. The 'binding' of IgE to particulate preparations derived from sonicated purified rat mast cells was measured by the blocking of PCA titrations of the supernatant solutions from incubations with such preparations. It was found that the PCA blocking reaction was inhibited by the addition of calcium ion to the incubations. The blocking reaction was strongly dependent on the pH of the incubations, being maximal at pH values lower than 5-0. The blocking reaction proceeded in a linear manner for at least 3 h provided that no more than 70 percent of the amount of IgE initially supplied had been removed by the particulate fraction. Only mast cell-derived preparations were capable of effecting PCA blocking."}
{"id": "PMID:2556", "title": "Effect of glucose and sucrose on survival in batch culture of Streptococcus mutans C67-1 and a noncariogenic mutant, C67-25.", "content": "The growth and survival of two strains of Streptococcus mutans in 5% (wt/vol) glucose or sucrose broth was investigated. S. mutans strain C67-1 showed little loss of viability after 30 h of incubation in batch culture in the presence of either sugar. S. mutans strain C67-25, a noncariogenic mutant of C67-1 that has lost the ability of the latter to produce sticky, insoluble extracellular polysaccharide when grown in sucrose broth, showed a dramatic loss of viability after 30 h of incubation in either glucose or sucrose broth, the effect being most marked in the presence of glucose. The loss of viability was shown to be due to acid production. Insoluble extracellular polysaccharide production appears to be a phenomenon favoring the survival of organisms subjected to high sucrose levels. Other factors must be involved, however, since there are differences between the two strains as regards their survival in glucose broth.", "contents": "Effect of glucose and sucrose on survival in batch culture of Streptococcus mutans C67-1 and a noncariogenic mutant, C67-25. The growth and survival of two strains of Streptococcus mutans in 5% (wt/vol) glucose or sucrose broth was investigated. S. mutans strain C67-1 showed little loss of viability after 30 h of incubation in batch culture in the presence of either sugar. S. mutans strain C67-25, a noncariogenic mutant of C67-1 that has lost the ability of the latter to produce sticky, insoluble extracellular polysaccharide when grown in sucrose broth, showed a dramatic loss of viability after 30 h of incubation in either glucose or sucrose broth, the effect being most marked in the presence of glucose. The loss of viability was shown to be due to acid production. Insoluble extracellular polysaccharide production appears to be a phenomenon favoring the survival of organisms subjected to high sucrose levels. Other factors must be involved, however, since there are differences between the two strains as regards their survival in glucose broth."}
{"id": "PMID:2557", "title": "Microcapsule of type III strains of group B Streptococcus: production and morphology.", "content": "The yield of purified type III polysaccharide of group B Streptococcus was significantly improved by modification of the growth medium. Culture of organisms in standard Todd-Hewitt broth resulted in acid accumulation during the exponential phase of growth and poor yield of type III polysaccharide when extracted from cells by washing with neutral buffer solution. By increasing the buffering capacity of the broth medium, acid accumulation was prevented, and the number of viable cells was increased at the stationary phase of growth. Further, by increasing the concentration of glucose in the buffered medium, the yield of type III polysaccharide was increased two to three times. Electron microscopic investigations of cells grown in the modified broth medium demonstrated a thicker microcapsule than was found in organisms grown in standard broth.", "contents": "Microcapsule of type III strains of group B Streptococcus: production and morphology. The yield of purified type III polysaccharide of group B Streptococcus was significantly improved by modification of the growth medium. Culture of organisms in standard Todd-Hewitt broth resulted in acid accumulation during the exponential phase of growth and poor yield of type III polysaccharide when extracted from cells by washing with neutral buffer solution. By increasing the buffering capacity of the broth medium, acid accumulation was prevented, and the number of viable cells was increased at the stationary phase of growth. Further, by increasing the concentration of glucose in the buffered medium, the yield of type III polysaccharide was increased two to three times. Electron microscopic investigations of cells grown in the modified broth medium demonstrated a thicker microcapsule than was found in organisms grown in standard broth."}
{"id": "PMID:2558", "title": "Central regulation of blood eosinophilia by the beta-adrenergic system in rats.", "content": "The effect of isoprenaline and three different beta-adrenergic blocking agents on blood eosinophilia was evaluated in the rat. Eosinopenic effect of isoprenaline was antagonized by intraperitoneal pretreatment with propranolol and by high but not low doses of practolol. Sotalol, a beta-blocker which in contrast to propranolol does not penetrate the blood-brain barrier, did not affect the eosinophil count when injected intraperitoneally, but produced a marked increase in number of circulating eosinophils following intracerebroventricular injection. Intraperitoneal administration of isoprenaline and propranolol as well as intracerebroventricular injection of sotalol did not affect eosinophil count in adrenalectomized or hypophysectomized rats. These results suggest that beta-adrenergic agents regulate the number of circulating eosinophils through a central mechanism and that presence of both hypophysis and adrenal glands is required for this action.", "contents": "Central regulation of blood eosinophilia by the beta-adrenergic system in rats. The effect of isoprenaline and three different beta-adrenergic blocking agents on blood eosinophilia was evaluated in the rat. Eosinopenic effect of isoprenaline was antagonized by intraperitoneal pretreatment with propranolol and by high but not low doses of practolol. Sotalol, a beta-blocker which in contrast to propranolol does not penetrate the blood-brain barrier, did not affect the eosinophil count when injected intraperitoneally, but produced a marked increase in number of circulating eosinophils following intracerebroventricular injection. Intraperitoneal administration of isoprenaline and propranolol as well as intracerebroventricular injection of sotalol did not affect eosinophil count in adrenalectomized or hypophysectomized rats. These results suggest that beta-adrenergic agents regulate the number of circulating eosinophils through a central mechanism and that presence of both hypophysis and adrenal glands is required for this action."}
{"id": "PMID:2559", "title": "Comparison between two antibody populations in the EBV system: anti-MA versus neutralizing antibody activity.", "content": "EBV-neutralizing antibody titers were determined in 11 sera derived from African Burkitt lymphoma or nasopharyngeal carcinoma patients and in the corresponding serum fractions retained above XM 100 Diaflo membranes after low pH treatment, and after recombination of the retained and passed fractions by neutralization of the acidified samples. They were compared with the corresponding antimembrane antigen (MA) titers in seven of the same sera. While all sera tested showed substantial increase of the anti-MA activity in the retained fraction, resulting in a significantly increased mean titer, EBV neutralizing activity did not change at all after identical treatment or changed only in a random fashion, resulting in stable mean titers. It is suggested that anti-MA and neutralizing antibodies are directed against at least partly different antigens on the virus.", "contents": "Comparison between two antibody populations in the EBV system: anti-MA versus neutralizing antibody activity. EBV-neutralizing antibody titers were determined in 11 sera derived from African Burkitt lymphoma or nasopharyngeal carcinoma patients and in the corresponding serum fractions retained above XM 100 Diaflo membranes after low pH treatment, and after recombination of the retained and passed fractions by neutralization of the acidified samples. They were compared with the corresponding antimembrane antigen (MA) titers in seven of the same sera. While all sera tested showed substantial increase of the anti-MA activity in the retained fraction, resulting in a significantly increased mean titer, EBV neutralizing activity did not change at all after identical treatment or changed only in a random fashion, resulting in stable mean titers. It is suggested that anti-MA and neutralizing antibodies are directed against at least partly different antigens on the virus."}
{"id": "PMID:2560", "title": "Gastric acid secretion, serum-gastrin levels and psychomotor function under the influence of placebo, insulin-hypoglycemia, and/or bromazepam.", "content": "Gastric acid output, blood-glucose, serum-gastrin and psychomotor-performance were measured in four healthy subjects one hour before and two hours after the intravenous injection of (a) 2ml saline, (b) 0.2 U/kg b.w. insulin, (c) 0.1 mg/kg b.w. bromazepam. Each subject underwent one experiment of each type. The study was layed out as a Latin-square and analysed accordingly. Gastric acid secretion was measured by means of intragastric titration and a telemetering capsule; blood-glucose and serum-gastrin levels as well as psychomotor performance as a measure of vigilance were determined in 15-minute-intervals. In the saline series (a), none of the four parameters showed any systematic variation. In series (b), a bimodal response of acid output to insulin, initial inhibition and subsequent stimulation was observed in all subjects. Serum-gastrin levels showed only a slight and transient increase in the first thirty minutes. Psychomotor performance decreased markedly with progressing hypoglycemia, and increased when glucose levels rose again. In the bromazepan series (c), acid output and psychomotor performance decreased and, after the first hour, increased almost parallely, while glucose and gastrin levels remained unchanged. In series (d), an additive effect of insulin and bromazepam occurred: acid output and psychomotor performance were lower than after insulin alone; peak acid secretion, maximal hypoglycemia and peak of serum-gastrin were shifted to the right. It is concluded that the lowered basal as well as insulin-stimulated acid secretion after bromazepam is due to the central effect of the drug, and that this effect is mediated to the gastric glands directly via autonomic nervous pathways without involving a release of endogenous gastrin.", "contents": "Gastric acid secretion, serum-gastrin levels and psychomotor function under the influence of placebo, insulin-hypoglycemia, and/or bromazepam. Gastric acid output, blood-glucose, serum-gastrin and psychomotor-performance were measured in four healthy subjects one hour before and two hours after the intravenous injection of (a) 2ml saline, (b) 0.2 U/kg b.w. insulin, (c) 0.1 mg/kg b.w. bromazepam. Each subject underwent one experiment of each type. The study was layed out as a Latin-square and analysed accordingly. Gastric acid secretion was measured by means of intragastric titration and a telemetering capsule; blood-glucose and serum-gastrin levels as well as psychomotor performance as a measure of vigilance were determined in 15-minute-intervals. In the saline series (a), none of the four parameters showed any systematic variation. In series (b), a bimodal response of acid output to insulin, initial inhibition and subsequent stimulation was observed in all subjects. Serum-gastrin levels showed only a slight and transient increase in the first thirty minutes. Psychomotor performance decreased markedly with progressing hypoglycemia, and increased when glucose levels rose again. In the bromazepan series (c), acid output and psychomotor performance decreased and, after the first hour, increased almost parallely, while glucose and gastrin levels remained unchanged. In series (d), an additive effect of insulin and bromazepam occurred: acid output and psychomotor performance were lower than after insulin alone; peak acid secretion, maximal hypoglycemia and peak of serum-gastrin were shifted to the right. It is concluded that the lowered basal as well as insulin-stimulated acid secretion after bromazepam is due to the central effect of the drug, and that this effect is mediated to the gastric glands directly via autonomic nervous pathways without involving a release of endogenous gastrin."}
{"id": "PMID:2561", "title": "[Correlation between plasma concentration and clinical effect of neuroleptics and antidepressants].", "content": "Results of investigations concerning the correlation between plasma concentrations and clinical effect of neuroleptics and antidepressives are summarised. In the case of neuroleptics there is in general no relationship between clinical parameters of activity and plasma concentration. For antidepressives there is, in most cases, a correlation between side-effects and plasma concentrations. Whether the therapeutic effect is dependent on the plasma concentration or not, is however open to some doubt. The practical value of plasma concentration estimations during therapy with the above mentioned drugs is therefore limited. Inadequate efficacy and/or poor tolerance can occasionally be explained by estimating plasma concentrations which alone, however, scarcely allow one to make prophecies. In determination of the optimal individual dosage must continue to be an empirical process based on clinical observations and experience.", "contents": "[Correlation between plasma concentration and clinical effect of neuroleptics and antidepressants]. Results of investigations concerning the correlation between plasma concentrations and clinical effect of neuroleptics and antidepressives are summarised. In the case of neuroleptics there is in general no relationship between clinical parameters of activity and plasma concentration. For antidepressives there is, in most cases, a correlation between side-effects and plasma concentrations. Whether the therapeutic effect is dependent on the plasma concentration or not, is however open to some doubt. The practical value of plasma concentration estimations during therapy with the above mentioned drugs is therefore limited. Inadequate efficacy and/or poor tolerance can occasionally be explained by estimating plasma concentrations which alone, however, scarcely allow one to make prophecies. In determination of the optimal individual dosage must continue to be an empirical process based on clinical observations and experience."}
{"id": "PMID:2563", "title": "EEG sleep studies of insomniacs under flunitrazepam treatment.", "content": "This study investigates the effect of flunitrazepam, a new benzodiazepine, on the sleep of insomniac patients under chronic treatment. Polygraphic recordings have shown that this drug decreases not only the activity of the wakefulness system, but also the activity of the synchronizing system of slow-wave sleep. The subjective feeling of improved and sounder sleep seems to be related to a decrease of wakefulness pressure as well as to a decrease of body motoricity, but not with the modification of sleep stages themselves. Flunitrazepam appears to possess some regulatory properties on REM sleep, since this stage is enhanced in patients with an initial low amount of REM sleep and decreased in those having a higher initial REM sleep. Flunitrazepam possesses potent and useful hypnogenic properties in man but does not induce physiological sleep.", "contents": "EEG sleep studies of insomniacs under flunitrazepam treatment. This study investigates the effect of flunitrazepam, a new benzodiazepine, on the sleep of insomniac patients under chronic treatment. Polygraphic recordings have shown that this drug decreases not only the activity of the wakefulness system, but also the activity of the synchronizing system of slow-wave sleep. The subjective feeling of improved and sounder sleep seems to be related to a decrease of wakefulness pressure as well as to a decrease of body motoricity, but not with the modification of sleep stages themselves. Flunitrazepam appears to possess some regulatory properties on REM sleep, since this stage is enhanced in patients with an initial low amount of REM sleep and decreased in those having a higher initial REM sleep. Flunitrazepam possesses potent and useful hypnogenic properties in man but does not induce physiological sleep."}
{"id": "PMID:2567", "title": "A histochemical study of the apparent deamination of proteins by sodium hypochlorite.", "content": "The possible chemical mechanisms by which neutral solutions of sodium hypochlorite containing a high concentration of sodium chloride abolish the acidophilia of proteins in sections of fixed tissue are reviewed. The most probable one is the chlorination of the protein terminal amino groups, followed by the breakdown of the N-chloramine so formed into alpha-ketocarboxylic acid, nitrile or aldehyde groups. Hypochlorite solutions certainly do not deaminate tissue sections as was previously thought. Experimental evidence for the formation of relatively stable N-chloramine groups in situ and their limited conversion to aldehydes is reported. For example, the acidophilia of hypochlorite-treated sections was found to be restored after flooding them with hydriodic acid followed by the extraction of the liberated iodine with an alcohol. The significance of these experimental findings is discussed.", "contents": "A histochemical study of the apparent deamination of proteins by sodium hypochlorite. The possible chemical mechanisms by which neutral solutions of sodium hypochlorite containing a high concentration of sodium chloride abolish the acidophilia of proteins in sections of fixed tissue are reviewed. The most probable one is the chlorination of the protein terminal amino groups, followed by the breakdown of the N-chloramine so formed into alpha-ketocarboxylic acid, nitrile or aldehyde groups. Hypochlorite solutions certainly do not deaminate tissue sections as was previously thought. Experimental evidence for the formation of relatively stable N-chloramine groups in situ and their limited conversion to aldehydes is reported. For example, the acidophilia of hypochlorite-treated sections was found to be restored after flooding them with hydriodic acid followed by the extraction of the liberated iodine with an alcohol. The significance of these experimental findings is discussed."}
{"id": "PMID:2568", "title": "Effects of dbcAMP and theophylline on rat adrenal medulla grown in tissue culture.", "content": "Explants of rat adrenal medulla were grown in tissue culture. The effects of various doses of dbcAMP ranging from 0.001 mM up to 1 mM and equimolar amounts of theophylline were recorded by phase contrast optics and catecholamine histochemistry (glyoxylic acid method) over six days. There was a dose-dependent inhibition of the normally occurring outgrowth of Schwann cells, \"chromaffin\" cells and axons from the explants. Maintenance of glyoxylic acid-induced fluorescence in \"chromaffin\" cells was dose-dependent, too. Since theophylline is known to enhance intracellular levels of cAMP only, these effects are probably due to the action of cAMP. cAMP obviously maintains the degree of differentiation of chromaffin cells. Thus it could be argued that a certain degree of dedifferentiation is a prerequisite for the formation of axons from these cells.", "contents": "Effects of dbcAMP and theophylline on rat adrenal medulla grown in tissue culture. Explants of rat adrenal medulla were grown in tissue culture. The effects of various doses of dbcAMP ranging from 0.001 mM up to 1 mM and equimolar amounts of theophylline were recorded by phase contrast optics and catecholamine histochemistry (glyoxylic acid method) over six days. There was a dose-dependent inhibition of the normally occurring outgrowth of Schwann cells, \"chromaffin\" cells and axons from the explants. Maintenance of glyoxylic acid-induced fluorescence in \"chromaffin\" cells was dose-dependent, too. Since theophylline is known to enhance intracellular levels of cAMP only, these effects are probably due to the action of cAMP. cAMP obviously maintains the degree of differentiation of chromaffin cells. Thus it could be argued that a certain degree of dedifferentiation is a prerequisite for the formation of axons from these cells."}
{"id": "PMID:2569", "title": "The possibilities and limitations of membrane methods for the histochemical demonstration of cholinesterases.", "content": "The thiocholine method for the histochemical detection of cholinesterases according to Karnovsky-Roots was adapted for unfixed cryostat sections by addition of the agar solution to the incubation mixture and by using the semipermeable membrane interposed between the section and the incubation medium. The procedure prevents the leakage of the enzyme activity of the section and is suitable for tissues where the cholinesterase activity is low.", "contents": "The possibilities and limitations of membrane methods for the histochemical demonstration of cholinesterases. The thiocholine method for the histochemical detection of cholinesterases according to Karnovsky-Roots was adapted for unfixed cryostat sections by addition of the agar solution to the incubation mixture and by using the semipermeable membrane interposed between the section and the incubation medium. The procedure prevents the leakage of the enzyme activity of the section and is suitable for tissues where the cholinesterase activity is low."}
{"id": "PMID:2565", "title": "Copper catalyzed alkaline autoxidation of selenocystamine.", "content": "In alkaline medium and in the presence of cupric ions selenocystamine undergoes autoxidation and is entirely transformed into selenohypotaurine. Among the different metal ions tested, Fe, Co, Ni, Cu, Ag, Mg, Mn, only cupric ions are effective in catalyzing the reaction. The reaction shows an optimum around pH 13. In most respects the autoxidation of selenocystamine is similar to the alkaline autoxidation of cystamine. Some data on the paper and ion exchange chromatographic behaviour of selenohypotaurine and selenotaurine are reported, as also details for the synthesis of selenotaurine.", "contents": "Copper catalyzed alkaline autoxidation of selenocystamine. In alkaline medium and in the presence of cupric ions selenocystamine undergoes autoxidation and is entirely transformed into selenohypotaurine. Among the different metal ions tested, Fe, Co, Ni, Cu, Ag, Mg, Mn, only cupric ions are effective in catalyzing the reaction. The reaction shows an optimum around pH 13. In most respects the autoxidation of selenocystamine is similar to the alkaline autoxidation of cystamine. Some data on the paper and ion exchange chromatographic behaviour of selenohypotaurine and selenotaurine are reported, as also details for the synthesis of selenotaurine."}
{"id": "PMID:2566", "title": "The binding of nucleotides to 3'-nucleotidase from wheat germ.", "content": "The 3'-mononucleotidase (3'-ribonucleotide phosphohydrolase, EC 3.1.3.6) from wheat germ has been purified 2,000 fold. The enzyme has a molecular weight of approximatley 32,000, as judged by the use of G-100 gel filtration, and does not attack 2'- or 5'- nucleotides. In order to obtain some indications on the structural requirements for binding and reactivity, the purified enzyme has been subjected to kinetic analyses, including initial velocities with several 3'-ribomononucleotides, inhibition by 5'- nucleotides and nucleotide-analogues, and effect of pH and sulphydryl compounds. The data indicate one base binding site at the active site of the enzyme. This site appears to be the same involved in the binding of both substrates and inhibitors, with higher affinity for purine nucleotides than for pyrimidine compounds, in the order guanosine greater than adenosine greater than inosine greater than uridine greater than cytidine nucleotides.", "contents": "The binding of nucleotides to 3'-nucleotidase from wheat germ. The 3'-mononucleotidase (3'-ribonucleotide phosphohydrolase, EC 3.1.3.6) from wheat germ has been purified 2,000 fold. The enzyme has a molecular weight of approximatley 32,000, as judged by the use of G-100 gel filtration, and does not attack 2'- or 5'- nucleotides. In order to obtain some indications on the structural requirements for binding and reactivity, the purified enzyme has been subjected to kinetic analyses, including initial velocities with several 3'-ribomononucleotides, inhibition by 5'- nucleotides and nucleotide-analogues, and effect of pH and sulphydryl compounds. The data indicate one base binding site at the active site of the enzyme. This site appears to be the same involved in the binding of both substrates and inhibitors, with higher affinity for purine nucleotides than for pyrimidine compounds, in the order guanosine greater than adenosine greater than inosine greater than uridine greater than cytidine nucleotides."}
{"id": "PMID:2570", "title": "Improved histological localization of GABA-transaminase activity in rat cerebellar cortex after aldehyde fixation.", "content": "A method for the chemical fixation of the enzyme GABA-transaminase in nervous tissue is described. It is shown that after perfusion with a formaldehyde/glutaraldehyde fixative, activity of the enzyme in cerebellar cortex is demonstrable whilst cellular morphology is preserved. Results from the improved technique have shown new sites of GABA-transaminase activity in cerebellar cortex. In view of these results a special function for glial cells in this area of brain has been suggested.", "contents": "Improved histological localization of GABA-transaminase activity in rat cerebellar cortex after aldehyde fixation. A method for the chemical fixation of the enzyme GABA-transaminase in nervous tissue is described. It is shown that after perfusion with a formaldehyde/glutaraldehyde fixative, activity of the enzyme in cerebellar cortex is demonstrable whilst cellular morphology is preserved. Results from the improved technique have shown new sites of GABA-transaminase activity in cerebellar cortex. In view of these results a special function for glial cells in this area of brain has been suggested."}
{"id": "PMID:2572", "title": "Effect of plasma [K+] on the DC potential and on ion distributions between CSF and blood.", "content": "Keeping the arterial pH at 7.4 and PaCO2 at 40 mmHg in eight anesthetized dogs, we acutely raised plasma potassium concentration from 3.4 to 8.2 meq/1, then allowed it to decay back to control levels. The cerebrospinal fluid (CSF)-blood electrical potential difference (pd) increased 13.2 mV per 10-fold increase in plasma [K+]. Again keeping arterial pH at 7.4 and PaCO2 at 40 mmHg, we elevated plasma [K+] in four dogs from 3.3 to 8.0 meq/1 and maintained this level for 6 h. We found 1) that the PD increased from a control value of +1.3 to +8.9mV, showing no tendency to decay over the 6 h; and 2) that the change in PD did not affect the distribution of Na+, K+, H+, Cl-, or HCO3- between blood and CSF over the 6 h. These results suggest that under these conditions the PD between CSF and blood may play no effective role in determining the distributions of these charged species by 6 h. These results are contrasted with recent findings which suggest that H+ and HCO3- are distributed according to passive forces between CSF and blood.", "contents": "Effect of plasma [K+] on the DC potential and on ion distributions between CSF and blood. Keeping the arterial pH at 7.4 and PaCO2 at 40 mmHg in eight anesthetized dogs, we acutely raised plasma potassium concentration from 3.4 to 8.2 meq/1, then allowed it to decay back to control levels. The cerebrospinal fluid (CSF)-blood electrical potential difference (pd) increased 13.2 mV per 10-fold increase in plasma [K+]. Again keeping arterial pH at 7.4 and PaCO2 at 40 mmHg, we elevated plasma [K+] in four dogs from 3.3 to 8.0 meq/1 and maintained this level for 6 h. We found 1) that the PD increased from a control value of +1.3 to +8.9mV, showing no tendency to decay over the 6 h; and 2) that the change in PD did not affect the distribution of Na+, K+, H+, Cl-, or HCO3- between blood and CSF over the 6 h. These results suggest that under these conditions the PD between CSF and blood may play no effective role in determining the distributions of these charged species by 6 h. These results are contrasted with recent findings which suggest that H+ and HCO3- are distributed according to passive forces between CSF and blood."}
{"id": "PMID:2573", "title": "Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb.", "content": "We examined fetal plasma corticoids and flow rate, electrolyte composition, and surfactant content of tracheal fluid in chronic experiments with eight fetal lambs. From 120 to 148 days of gestation the rate of fluid production was 4.5 ml/kg per h, and there was no change in mean fluid sodium (147.8 meq/1), chloride (153.1 meq/1), calcium (2.2 mg/100 ml), and pH (6.23). Tracheal fluid potassium increased from 4.3 meq/1 at 120-130 days to 8.9 meq/1 at term, while plasma sodium, chloride, calcium, pH, and potassium were constant at 146.1 meq/1, 110.0 meq/1, 12.1 mg/100 ml, 7.39, and 4.0 meq/1, respectively. Plasma corticoids were less than 1.5 mug/100 ml total (0.3 mug/100 ml free) until 130 days, when they increased rapidly to 10.5 total (3.2 free) at 148 days. Surfactant was first detected in tracheal fluid between 124 and 133 days and its secretion increased rapidly after 135 days to a value of 125 mug/kg per h at 148 days. A sudden increase in fetal plasma corticoids does not seem to be the stimulus for appearance of surfactant in the lamb, although these hormones may induce the rapid accumulation of surfactant prior to delivery.", "contents": "Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb. We examined fetal plasma corticoids and flow rate, electrolyte composition, and surfactant content of tracheal fluid in chronic experiments with eight fetal lambs. From 120 to 148 days of gestation the rate of fluid production was 4.5 ml/kg per h, and there was no change in mean fluid sodium (147.8 meq/1), chloride (153.1 meq/1), calcium (2.2 mg/100 ml), and pH (6.23). Tracheal fluid potassium increased from 4.3 meq/1 at 120-130 days to 8.9 meq/1 at term, while plasma sodium, chloride, calcium, pH, and potassium were constant at 146.1 meq/1, 110.0 meq/1, 12.1 mg/100 ml, 7.39, and 4.0 meq/1, respectively. Plasma corticoids were less than 1.5 mug/100 ml total (0.3 mug/100 ml free) until 130 days, when they increased rapidly to 10.5 total (3.2 free) at 148 days. Surfactant was first detected in tracheal fluid between 124 and 133 days and its secretion increased rapidly after 135 days to a value of 125 mug/kg per h at 148 days. A sudden increase in fetal plasma corticoids does not seem to be the stimulus for appearance of surfactant in the lamb, although these hormones may induce the rapid accumulation of surfactant prior to delivery."}
{"id": "PMID:2574", "title": "Hydrogen ion concentration and oxygen uptake in an isolated canine hindlimb.", "content": "Oxygen utilization (VO2) and lactate production by an isolated perfused canine hindlimb was evaluated at various hydrogen ion concentrations. A membrane lung perfusion system was established such that blood flow and temperature could be fixed at normal levels. Oxygen, nitrogen, and carbon dioxide (CO2) gas flows to the membrane lung were independently regulated to provide a fixed arterial oxygen content (CaO2). By changing CO2 flow, the pH of the arterial blood was varied between 6.9 and 7.6 at 10-min intervals. The mean O2 delivery (CaO2 X blood flow) was between 16.3 ML O2/min and 20.5 ml O2/min. Standard error of the mean in each dog, however, was less than 0.4 ml O2/min. VO2 was linearly related to the pH of the perfusing blood: VO2% = 100.1 pH - 643 (r = 0.866). Oxygen consumption was inversely related to PCO2: VO2% = -0.62 PCO2 + 124, but the correlation was less good (r = 0.729). Lactate production was linearly related to the pH of the perfusing blood (above a pH of 7.4): lactate produced = 22.5 pH - 162.5 (r = 0.75). At a pH below 7.4, lactate was not produced. Oxygen consumption of skeletal muscle appears critically dependent on extracellular fluid pH. A change in pH of 0.1 alters VO2 almost exactly 10%. Alkalosis is a potent stimulus to lactic acid production by skeletal muscle.", "contents": "Hydrogen ion concentration and oxygen uptake in an isolated canine hindlimb. Oxygen utilization (VO2) and lactate production by an isolated perfused canine hindlimb was evaluated at various hydrogen ion concentrations. A membrane lung perfusion system was established such that blood flow and temperature could be fixed at normal levels. Oxygen, nitrogen, and carbon dioxide (CO2) gas flows to the membrane lung were independently regulated to provide a fixed arterial oxygen content (CaO2). By changing CO2 flow, the pH of the arterial blood was varied between 6.9 and 7.6 at 10-min intervals. The mean O2 delivery (CaO2 X blood flow) was between 16.3 ML O2/min and 20.5 ml O2/min. Standard error of the mean in each dog, however, was less than 0.4 ml O2/min. VO2 was linearly related to the pH of the perfusing blood: VO2% = 100.1 pH - 643 (r = 0.866). Oxygen consumption was inversely related to PCO2: VO2% = -0.62 PCO2 + 124, but the correlation was less good (r = 0.729). Lactate production was linearly related to the pH of the perfusing blood (above a pH of 7.4): lactate produced = 22.5 pH - 162.5 (r = 0.75). At a pH below 7.4, lactate was not produced. Oxygen consumption of skeletal muscle appears critically dependent on extracellular fluid pH. A change in pH of 0.1 alters VO2 almost exactly 10%. Alkalosis is a potent stimulus to lactic acid production by skeletal muscle."}
{"id": "PMID:2575", "title": "Cerebrospinal fluid sampling technique and Astrup pH and PCO2 values.", "content": "The pH and PCO2 values measured by the Astrup technique were compared in cerebrospinal fluid (CSF) obtained using two different sampling techniques: 1) a direct or in vivo technique and 2) the widely accepted syringe sampling technique. In 65 pairs of measurements in 9 dogs it was found that the pH was always overestimated and the PCO2 always underestimated in the syringe sample when compared to the in vivo sample. The equations describing the relationships are as follows: 1) pH (syringe = 0.995 pH (in vivo) + 0.084 and 2) PCO2 (syringe) = 0.873 PCO2 (in vivo) + 0.2. The amount by which the syringe sample underestimated the true PCO2 value increased with the absolute PCO2 value, consistent with the possibility of there being a diffusional loss of CO2 during the transfer of CSF from the syringe to the pH electrode (PCO2 (in vivo)- PCO2 (syringe) = 2.4, 4.9, 7.5, and 10.0 mmHg at in vivo PCO2's of 20, 40, 60, and 80 mmHg). This study indicates that the technique used for sampling CSF is crucial to the expected accuracy of the results and that the number of transfers of CSF during the sampling and measurement procedures should be minimized in order to obtain reliable results.", "contents": "Cerebrospinal fluid sampling technique and Astrup pH and PCO2 values. The pH and PCO2 values measured by the Astrup technique were compared in cerebrospinal fluid (CSF) obtained using two different sampling techniques: 1) a direct or in vivo technique and 2) the widely accepted syringe sampling technique. In 65 pairs of measurements in 9 dogs it was found that the pH was always overestimated and the PCO2 always underestimated in the syringe sample when compared to the in vivo sample. The equations describing the relationships are as follows: 1) pH (syringe = 0.995 pH (in vivo) + 0.084 and 2) PCO2 (syringe) = 0.873 PCO2 (in vivo) + 0.2. The amount by which the syringe sample underestimated the true PCO2 value increased with the absolute PCO2 value, consistent with the possibility of there being a diffusional loss of CO2 during the transfer of CSF from the syringe to the pH electrode (PCO2 (in vivo)- PCO2 (syringe) = 2.4, 4.9, 7.5, and 10.0 mmHg at in vivo PCO2's of 20, 40, 60, and 80 mmHg). This study indicates that the technique used for sampling CSF is crucial to the expected accuracy of the results and that the number of transfers of CSF during the sampling and measurement procedures should be minimized in order to obtain reliable results."}
{"id": "PMID:2576", "title": "Hypoventilation in ponies after carotid body denervation.", "content": "Seven ponies were subjected to carotid body denervation (CD) and two ponies were sham operated (S). Measurement of arterial blood gases and arterial blood and cerebrospinal fluid (CSF) acid-base balance were made prior to and 1,2,4,9, and 17 wks after surgery in unanesthetized animals. Resting ventilation and ventilatory responsiveness to hypoxia and NaCN infusion were assessed prior to and 2,9, and 17  wks after surgery. Alveolar hypoventilation in the CD ponies was marked 1-2 wk after surgery when VE and VA were reduced 40% and 10%, respectively, from control and PaCO2 was 12-15 mmHg above control. However, the effect was not nearly as great 4, 9, and 17 wk after surgery when the PaCO2 stabilized at approximately 6 mmHg above control PaCO2. Arterial blood pH was normal in the hypercapnic CD ponies, but CSF pH remained acid relative to normal throughout the 17-wk period. Changes in ventilatory responsiveness to hypoxia and NaCN tended to parallel changes in resting ventilation. These findings suggest: 1) the carotid bodies are essential in ponies to maintain normal ventilation: 2) in CD ponies peripheral chemosensitivity is partially regained at some unestablished locus; and 3) pH compensating mechanisms in chronically hypercapnic ponies function relatively better in blood than in CSF.", "contents": "Hypoventilation in ponies after carotid body denervation. Seven ponies were subjected to carotid body denervation (CD) and two ponies were sham operated (S). Measurement of arterial blood gases and arterial blood and cerebrospinal fluid (CSF) acid-base balance were made prior to and 1,2,4,9, and 17 wks after surgery in unanesthetized animals. Resting ventilation and ventilatory responsiveness to hypoxia and NaCN infusion were assessed prior to and 2,9, and 17  wks after surgery. Alveolar hypoventilation in the CD ponies was marked 1-2 wk after surgery when VE and VA were reduced 40% and 10%, respectively, from control and PaCO2 was 12-15 mmHg above control. However, the effect was not nearly as great 4, 9, and 17 wk after surgery when the PaCO2 stabilized at approximately 6 mmHg above control PaCO2. Arterial blood pH was normal in the hypercapnic CD ponies, but CSF pH remained acid relative to normal throughout the 17-wk period. Changes in ventilatory responsiveness to hypoxia and NaCN tended to parallel changes in resting ventilation. These findings suggest: 1) the carotid bodies are essential in ponies to maintain normal ventilation: 2) in CD ponies peripheral chemosensitivity is partially regained at some unestablished locus; and 3) pH compensating mechanisms in chronically hypercapnic ponies function relatively better in blood than in CSF."}
{"id": "PMID:2577", "title": "Total and regional cerebral blood flow during moderate and severe exercise in miniature swine.", "content": "To determine the influence of exercise on cerebral blood flow, we ran 14 swine at 3-6 mph and at 0-10% grades on a treadmill for 30 min at moderate and severe levels of exercise. Measuring heart rate, cardiac output, and aortic pressure via implanted probes, we injected 15-mum radiolabeled microspheres via the left atrium before and during exercise. We measured their distribution by gamma spectrometry, determining total cerebral blood flow, regional blood flow, and ratio of flow to gray and white matter. Heart rate, cardiac output, and aortic pressure rose progressively with increasing exercise. Total cerebral flow resembled that reported in humans, i.e., it did not change significantly with exercise. Regional flow distribution also failed to change significantly with exercise. The ratio of gray to white matter flow did not change except to the cerebellum where it rose significantly from resting values at both moderate and severe exercise. Gray matter received more flow than white matter during all three conditions of observation. Cerebral blood flow was remarkably constant during even severe exercise.", "contents": "Total and regional cerebral blood flow during moderate and severe exercise in miniature swine. To determine the influence of exercise on cerebral blood flow, we ran 14 swine at 3-6 mph and at 0-10% grades on a treadmill for 30 min at moderate and severe levels of exercise. Measuring heart rate, cardiac output, and aortic pressure via implanted probes, we injected 15-mum radiolabeled microspheres via the left atrium before and during exercise. We measured their distribution by gamma spectrometry, determining total cerebral blood flow, regional blood flow, and ratio of flow to gray and white matter. Heart rate, cardiac output, and aortic pressure rose progressively with increasing exercise. Total cerebral flow resembled that reported in humans, i.e., it did not change significantly with exercise. Regional flow distribution also failed to change significantly with exercise. The ratio of gray to white matter flow did not change except to the cerebellum where it rose significantly from resting values at both moderate and severe exercise. Gray matter received more flow than white matter during all three conditions of observation. Cerebral blood flow was remarkably constant during even severe exercise."}
{"id": "PMID:2578", "title": "Method for measuring hepatic uptake of oxygen or other blood-borne substances in situ.", "content": "A preparation is described by which hepatic arterial blood flow and portal venous blood flow can be accurately and continuously measured while simultaneously providing a method by which multiple blood samples can be taken from the hepatic artery, portal vein, and hepatic vein without disrupting hepatic hemodynamics or causing hemodilution. By this means hepatic uptake or release of blood-borne substances can be measured in situ and correlated with hemodynamic parameters. In 13 splenectomized cats, oxygen uptake by the denervated liver was 4.5 +/- 0.3 ml . min-1. 100 g-1 of tissue, representing 54% of total oxygen removed by the splanchnic bed. The hepatic hemodynamics determined by this method are similar to those reported by others in vivo and the metabolic state of the liver remained stable for at least 2 h during which an average of 29 blood samples were taken. Advantages of this preparation over other methods of obtaining similar data are discussed.", "contents": "Method for measuring hepatic uptake of oxygen or other blood-borne substances in situ. A preparation is described by which hepatic arterial blood flow and portal venous blood flow can be accurately and continuously measured while simultaneously providing a method by which multiple blood samples can be taken from the hepatic artery, portal vein, and hepatic vein without disrupting hepatic hemodynamics or causing hemodilution. By this means hepatic uptake or release of blood-borne substances can be measured in situ and correlated with hemodynamic parameters. In 13 splenectomized cats, oxygen uptake by the denervated liver was 4.5 +/- 0.3 ml . min-1. 100 g-1 of tissue, representing 54% of total oxygen removed by the splanchnic bed. The hepatic hemodynamics determined by this method are similar to those reported by others in vivo and the metabolic state of the liver remained stable for at least 2 h during which an average of 29 blood samples were taken. Advantages of this preparation over other methods of obtaining similar data are discussed."}
{"id": "PMID:2579", "title": "Analysis of pesticide residues by chemical derivatization. II. N-methylcarbamates in natural water and soils.", "content": "A method for the quantitative determination of several N-methylcarbamates in natural waters and the applicability of the derivative to soil samples using a previously published extraction procedure are described. After extraction of the carbamates from the substrate, the carbamates are hydrolyzed in a 10% methanol-potassium hydroxide solution to form the phenolic hydrolysis products, which are isolated and derivatized with pentafluorobenzyl (PFB) bromide to produce the PFB ether derivatives. The PFB derivatives are cleaned up and fractionated on a silica gel microcolumn and determined by electron capture gas-liquid chromatography (GLC). Eight organophosphate pesticides and 2 phthalate acid esters that hydrolyze to phenols or phthalic acid were evaluated as potential interferences and were found not to interfere with any of the carbamates tested. Quantitative determinations of 0.1 mug carbofuran and 3-ketocarbofuran and 0.5 mug carbaryl, metmercapturon, and Mobam in a 1 L water sample are possible. Propoxur was not determined at levels less than 1 mug/L due to the short GLC retention time of the derivative and interferences from the reagents at the lower levels.", "contents": "Analysis of pesticide residues by chemical derivatization. II. N-methylcarbamates in natural water and soils. A method for the quantitative determination of several N-methylcarbamates in natural waters and the applicability of the derivative to soil samples using a previously published extraction procedure are described. After extraction of the carbamates from the substrate, the carbamates are hydrolyzed in a 10% methanol-potassium hydroxide solution to form the phenolic hydrolysis products, which are isolated and derivatized with pentafluorobenzyl (PFB) bromide to produce the PFB ether derivatives. The PFB derivatives are cleaned up and fractionated on a silica gel microcolumn and determined by electron capture gas-liquid chromatography (GLC). Eight organophosphate pesticides and 2 phthalate acid esters that hydrolyze to phenols or phthalic acid were evaluated as potential interferences and were found not to interfere with any of the carbamates tested. Quantitative determinations of 0.1 mug carbofuran and 3-ketocarbofuran and 0.5 mug carbaryl, metmercapturon, and Mobam in a 1 L water sample are possible. Propoxur was not determined at levels less than 1 mug/L due to the short GLC retention time of the derivative and interferences from the reagents at the lower levels."}
{"id": "PMID:2580", "title": "Separation of pesticide residues from lipids prior to gas-liquid chromatographic analysis.", "content": "Lipids are separated from dieldrin, endrin, and p,p'-DDE residues by saponification in ethanolic sodium hydroxide, acidification with dilute sulfuric acid, and adsorption chromatography on deactivated alumina, using petroleum ether as the eluant. Dieldrin, endrin, and p,p'-DDE are efficiently recovered (95-102%), and p,p'-DDT is converted to p,p'-DDE, which is then recovered with high yield (90-96%). Extremely low lipid carryover (less than 0.3-0.5%) is observed for 0.5-1.0 g samples of chicken fat.", "contents": "Separation of pesticide residues from lipids prior to gas-liquid chromatographic analysis. Lipids are separated from dieldrin, endrin, and p,p'-DDE residues by saponification in ethanolic sodium hydroxide, acidification with dilute sulfuric acid, and adsorption chromatography on deactivated alumina, using petroleum ether as the eluant. Dieldrin, endrin, and p,p'-DDE are efficiently recovered (95-102%), and p,p'-DDT is converted to p,p'-DDE, which is then recovered with high yield (90-96%). Extremely low lipid carryover (less than 0.3-0.5%) is observed for 0.5-1.0 g samples of chicken fat."}
{"id": "PMID:2581", "title": "Collaborative study of the Food Chemicals Codex method for the determination of the neutralizing value of sodium aluminum phosphate.", "content": "Fifteen laboratories participated in a collaborative study to evaluate the Food Chemicals Codex method for the determination of the neutralizing value of sodium aluminum phosphate. The AOAC method for determining the neutralizing value of sodium acid pyrophosphate, sec. 8.010, was also included in the study. The precisions of the Food chemicals Codex method, based on the between-replicate standard deviation and on one collaborator making one determination, are 1.16 and 3.66, respectively. The Food Chemicals Codex method for the determination of the neutralizing value of sodium aluminum phosphate has been adopted as official first action.", "contents": "Collaborative study of the Food Chemicals Codex method for the determination of the neutralizing value of sodium aluminum phosphate. Fifteen laboratories participated in a collaborative study to evaluate the Food Chemicals Codex method for the determination of the neutralizing value of sodium aluminum phosphate. The AOAC method for determining the neutralizing value of sodium acid pyrophosphate, sec. 8.010, was also included in the study. The precisions of the Food chemicals Codex method, based on the between-replicate standard deviation and on one collaborator making one determination, are 1.16 and 3.66, respectively. The Food Chemicals Codex method for the determination of the neutralizing value of sodium aluminum phosphate has been adopted as official first action."}
{"id": "PMID:2582", "title": "Affinity chromatography of trypsin and related enzymes. I. Preparation and characteristics of an affinity adsorbent containing tryptic peptides from protamine as ligands.", "content": "An absorbent for the affinity chromatography of trypsin [EC 3.4.21.4] (AP Sepharose) was prepared. The ligand was a mixture of oligopeptides (mainly di- and tripeptides) containing L-arginine as carboxyl termini, and was obtained from a tryptic digest of protamine. Trypsin was absorbed at relatively low pH (7-4), but was not absorbed at the optimum pH of catalysis (8.2). This was clearly explained on the basis of the pH dependence of the interaction of trypsin with its products. Inactivated trypsin, trypsinogen, and chymotrypsin were not absorbed. The absorption of active trypsin was interferred with by either benzamidine or urea. From these observations, it is evident that AP Sepharose is an affinity adsorbent. AP Sepharose was useful for purification of commercial bovine trypsin. A preliminary application for the purification of Streptomyces griseus trypsin was also successful.", "contents": "Affinity chromatography of trypsin and related enzymes. I. Preparation and characteristics of an affinity adsorbent containing tryptic peptides from protamine as ligands. An absorbent for the affinity chromatography of trypsin [EC 3.4.21.4] (AP Sepharose) was prepared. The ligand was a mixture of oligopeptides (mainly di- and tripeptides) containing L-arginine as carboxyl termini, and was obtained from a tryptic digest of protamine. Trypsin was absorbed at relatively low pH (7-4), but was not absorbed at the optimum pH of catalysis (8.2). This was clearly explained on the basis of the pH dependence of the interaction of trypsin with its products. Inactivated trypsin, trypsinogen, and chymotrypsin were not absorbed. The absorption of active trypsin was interferred with by either benzamidine or urea. From these observations, it is evident that AP Sepharose is an affinity adsorbent. AP Sepharose was useful for purification of commercial bovine trypsin. A preliminary application for the purification of Streptomyces griseus trypsin was also successful."}
{"id": "PMID:2583", "title": "Effects on tryptophyl absorption of the ionization of the catalytic carboxyls in hen and turkey lysozymes.", "content": "The difference spectra of hen and turkey egg-white lysozymes [EC 3.2.1.17] produced by acidification were measured. The difference spectra of both lysozymes had peaks at 295 and 301 nm which are characteristic of tryptophyl residues. The pH dependence curves of the extinction differences (delta eplision) at 301 nm and 295 nm for hen lysozyme were identical with the corresponding curves for turkey lysozyme. The pH dependence of delta eplision at 301 nm was analyzed assuming that the extinction at 301 nm is due to Trp 108 only, which interacts with the catalytic carboxyls, Glu 35 and Asp 52.  The macroscopic pK values of Glu 35 and Asp 52 in both lysozymes thus determined were 6.0 and 3.3, respectively. These values were in excellent agreement with those determined by measuring the pH dependence of the circular dichroic band at 305 nm (Kuramitsu et al. (1974) J. Biochem, 76, 671-683; (1975) ibid. 77, 291-301). The pH dependence of delta eplision at 295 nm could not be completely explained in terms of the electrostatic effects of the catalytic groups on Trp 108.", "contents": "Effects on tryptophyl absorption of the ionization of the catalytic carboxyls in hen and turkey lysozymes. The difference spectra of hen and turkey egg-white lysozymes [EC 3.2.1.17] produced by acidification were measured. The difference spectra of both lysozymes had peaks at 295 and 301 nm which are characteristic of tryptophyl residues. The pH dependence curves of the extinction differences (delta eplision) at 301 nm and 295 nm for hen lysozyme were identical with the corresponding curves for turkey lysozyme. The pH dependence of delta eplision at 301 nm was analyzed assuming that the extinction at 301 nm is due to Trp 108 only, which interacts with the catalytic carboxyls, Glu 35 and Asp 52.  The macroscopic pK values of Glu 35 and Asp 52 in both lysozymes thus determined were 6.0 and 3.3, respectively. These values were in excellent agreement with those determined by measuring the pH dependence of the circular dichroic band at 305 nm (Kuramitsu et al. (1974) J. Biochem, 76, 671-683; (1975) ibid. 77, 291-301). The pH dependence of delta eplision at 295 nm could not be completely explained in terms of the electrostatic effects of the catalytic groups on Trp 108."}
{"id": "PMID:2584", "title": "Resonance Raman scattering from hemoproteins. Effects of ligands upon the Raman spectra of various C-type cytochromes.", "content": "Resonance Raman spectra were measured for various C-type cytochromes (mammalian cytochrome c, bacterial cytochrome c3, algal photosynthetic cytochrome f, and alkylated cytochrome c) and a B-type cytochrome (cytochrome b5) in their reduced and oxidized states. (1) For ferrous alkylated cytochrome c, a Raman line sensitive to the replacement of an axial ligand of the heme iron uas found around 1540 cm=1. This ligand-sensitive Raman line indicated the transition from acidic (1545 cm-1) to alkaline (1533 cm-1) forms with pK 7.9. The pH dependence of the Raman spectrum corresponded well to that of the optical absorption spectra. (2) For ferrous cytochrome f, the ligand-sensitive Raman line was found at the same frequency as cytochrome c (1545 cm-1). Accordingly two axial ligands are likely to be histidine and methionine as in cytochrome c. (3) For ferrous cytochrome c3, the frequency of the ligand-sensitive Raman line was between those of cytochrome c and cytochrome b5. Since two axial ligands of the heme iron in cytochrome c3 might be histidines. However, a combination of histidine and methionine as a possible set of two axial ligands was not completely excluded for one or two of the four hemes. (4) In ferrous cytochrome b5, two weak Raman lines appeared at 1302 and 1338 cm-1 instead of the strongest band at 1313 cm-1 of C-type ferrous cytochromes. This suggests the practical use of these bands for the identification of types of cytochromes. The difference in frequency and intensity between B- and C-types of hemes implies that the low effective symmetry of the heme in ferrous cytochrome c is due to vibrational coupling of ring modes with peripheral substituents rather than geometrical disortion of heme.", "contents": "Resonance Raman scattering from hemoproteins. Effects of ligands upon the Raman spectra of various C-type cytochromes. Resonance Raman spectra were measured for various C-type cytochromes (mammalian cytochrome c, bacterial cytochrome c3, algal photosynthetic cytochrome f, and alkylated cytochrome c) and a B-type cytochrome (cytochrome b5) in their reduced and oxidized states. (1) For ferrous alkylated cytochrome c, a Raman line sensitive to the replacement of an axial ligand of the heme iron uas found around 1540 cm=1. This ligand-sensitive Raman line indicated the transition from acidic (1545 cm-1) to alkaline (1533 cm-1) forms with pK 7.9. The pH dependence of the Raman spectrum corresponded well to that of the optical absorption spectra. (2) For ferrous cytochrome f, the ligand-sensitive Raman line was found at the same frequency as cytochrome c (1545 cm-1). Accordingly two axial ligands are likely to be histidine and methionine as in cytochrome c. (3) For ferrous cytochrome c3, the frequency of the ligand-sensitive Raman line was between those of cytochrome c and cytochrome b5. Since two axial ligands of the heme iron in cytochrome c3 might be histidines. However, a combination of histidine and methionine as a possible set of two axial ligands was not completely excluded for one or two of the four hemes. (4) In ferrous cytochrome b5, two weak Raman lines appeared at 1302 and 1338 cm-1 instead of the strongest band at 1313 cm-1 of C-type ferrous cytochromes. This suggests the practical use of these bands for the identification of types of cytochromes. The difference in frequency and intensity between B- and C-types of hemes implies that the low effective symmetry of the heme in ferrous cytochrome c is due to vibrational coupling of ring modes with peripheral substituents rather than geometrical disortion of heme."}
{"id": "PMID:2585", "title": "Studies on the microsomal electron-transport system of anaerobically grown yeast. III. Spectral characterization of cytochrome P-450.", "content": "A carbon monoxide-binding pigment which shows an absorption peak at about 450 nm in the reduced carbon monoxide difference spectrum was purified from the microsomal fraction of yeast grown anaerobically. The spectral characteristics of the pigment were practically identical with those of cytochrome P-450 of hepatic microsomes, especially from polycyclic hydrocarbon-induced animals. The pigment was denatured to P-420, and bound with ethyl isocyanide in the reduced state. Although Type I spectral change was not evident, the pigment showed Type II and modified Type II spectral changes upon binding with some organic compounds, as in the case of hepatic cytochrome P-450. These observations clearly indicate that the carbon monoxide-binding pigment of yeast microsomes may be designated as cytochrome P-450 of yeast.", "contents": "Studies on the microsomal electron-transport system of anaerobically grown yeast. III. Spectral characterization of cytochrome P-450. A carbon monoxide-binding pigment which shows an absorption peak at about 450 nm in the reduced carbon monoxide difference spectrum was purified from the microsomal fraction of yeast grown anaerobically. The spectral characteristics of the pigment were practically identical with those of cytochrome P-450 of hepatic microsomes, especially from polycyclic hydrocarbon-induced animals. The pigment was denatured to P-420, and bound with ethyl isocyanide in the reduced state. Although Type I spectral change was not evident, the pigment showed Type II and modified Type II spectral changes upon binding with some organic compounds, as in the case of hepatic cytochrome P-450. These observations clearly indicate that the carbon monoxide-binding pigment of yeast microsomes may be designated as cytochrome P-450 of yeast."}
{"id": "PMID:2586", "title": "Polarographic studies on ubiquinone-10 and rhodoquinone bound with chromatophores from Rhodospirillum rubrum.", "content": "Redox components bound with chromatophores of Rhodospirillum rubrum, and pure samples of ubiquinone-10 and rhodoquinone were studied polarographically at 24 degrees. In a mixture of ethanol and water (4 : 1, v/v) at pH 7, ubiquinone-10 and rhodoquinone had half-wave potentials (E1/2) OF +43 MV and -63 mV, respectively. For both quinones, values of the electron transfer number (n) were 2 , and plots of E1/2 versus pH formed straight lines with slopes of -30 mV/pH in the neutral pH range; thus, values of the proton transfer number (n-a) were estimated to be 1 for both quinones. When bound with chromatophores, ubiquinone-10 and rhodoquinone had E1/2 values of +50 mV (n=2) and -30 mV (n=2), respectively, at pH 7. Values of (n-a) were estimated to be 1 for ubiquinone-10 and 2 for rhodoquinone. A component (POC-170) thought to be one of the active center bacteriochlorophylls (Liac-890) was characterized; it has E1/2 value of -170 mV at pH 7 and its oxidation-reduction is possibly brought about by dehydrogenation-hydrogenation. Conceivably, the oxidation-reduction sites of ubiquinone-10, rhodoquinone and POC-170 partly, if not all, exist on the surface of chromatophore membrane or project outside the membrane, because of their accessibility to the polarographic electrode.", "contents": "Polarographic studies on ubiquinone-10 and rhodoquinone bound with chromatophores from Rhodospirillum rubrum. Redox components bound with chromatophores of Rhodospirillum rubrum, and pure samples of ubiquinone-10 and rhodoquinone were studied polarographically at 24 degrees. In a mixture of ethanol and water (4 : 1, v/v) at pH 7, ubiquinone-10 and rhodoquinone had half-wave potentials (E1/2) OF +43 MV and -63 mV, respectively. For both quinones, values of the electron transfer number (n) were 2 , and plots of E1/2 versus pH formed straight lines with slopes of -30 mV/pH in the neutral pH range; thus, values of the proton transfer number (n-a) were estimated to be 1 for both quinones. When bound with chromatophores, ubiquinone-10 and rhodoquinone had E1/2 values of +50 mV (n=2) and -30 mV (n=2), respectively, at pH 7. Values of (n-a) were estimated to be 1 for ubiquinone-10 and 2 for rhodoquinone. A component (POC-170) thought to be one of the active center bacteriochlorophylls (Liac-890) was characterized; it has E1/2 value of -170 mV at pH 7 and its oxidation-reduction is possibly brought about by dehydrogenation-hydrogenation. Conceivably, the oxidation-reduction sites of ubiquinone-10, rhodoquinone and POC-170 partly, if not all, exist on the surface of chromatophore membrane or project outside the membrane, because of their accessibility to the polarographic electrode."}
{"id": "PMID:2587", "title": "Effect of metal ions in the culture medium on the stearoyl-coenzyme A desaturase activity of Mycobacterium phlei.", "content": "A particulate fraction prepared from Mycobacterium phlei grown in a metal-deficient medium exhibited a greatly reduced activity of stearoyl-CoA desaturase compared to that from normally grown cells. Metal deficiency, however, had no effect on the FAD-dependent NADPH-cytochrome C reductase activity, which has been suggested to participate in the desaturation process. When the cells were grown in the deficient medium supplemented with both Fe2+ and Mg2+, the desaturase activity was restored to the normal level. Supplementation with Mg2+ alone promoted growth but did not restore the desaturase activity, whereas Fe2+ alone did cause a significant restoration. Among the various metal ions tested, only Fe2+ and Fe3+ enhanced the formation of desaturase activity in the deficient medium. When added to the assay medium in vitro, Fe2+ and Fe3+ did not stimulate the desaturase activity of the particulate fraction from the deficient cells. Cultivation in the metal-deficient medium had essentially no effect on the levels of cytochromes in the particulate fraction, but dramatically decreased the non-heme iron content and the amount of a high-spin ferric species exhibiting an ESR signal at g=4.3. No labile sulfur could be detected in the normal or metal-deficient particulate fractions. It is concluded that the presence of iron ions in the culture medium is necessary for the synthesis and/or assembly of the terminal portion of the desaturase system.", "contents": "Effect of metal ions in the culture medium on the stearoyl-coenzyme A desaturase activity of Mycobacterium phlei. A particulate fraction prepared from Mycobacterium phlei grown in a metal-deficient medium exhibited a greatly reduced activity of stearoyl-CoA desaturase compared to that from normally grown cells. Metal deficiency, however, had no effect on the FAD-dependent NADPH-cytochrome C reductase activity, which has been suggested to participate in the desaturation process. When the cells were grown in the deficient medium supplemented with both Fe2+ and Mg2+, the desaturase activity was restored to the normal level. Supplementation with Mg2+ alone promoted growth but did not restore the desaturase activity, whereas Fe2+ alone did cause a significant restoration. Among the various metal ions tested, only Fe2+ and Fe3+ enhanced the formation of desaturase activity in the deficient medium. When added to the assay medium in vitro, Fe2+ and Fe3+ did not stimulate the desaturase activity of the particulate fraction from the deficient cells. Cultivation in the metal-deficient medium had essentially no effect on the levels of cytochromes in the particulate fraction, but dramatically decreased the non-heme iron content and the amount of a high-spin ferric species exhibiting an ESR signal at g=4.3. No labile sulfur could be detected in the normal or metal-deficient particulate fractions. It is concluded that the presence of iron ions in the culture medium is necessary for the synthesis and/or assembly of the terminal portion of the desaturase system."}
{"id": "PMID:2589", "title": "Photoaffinity labeling of concanavalin A. Preparation of a concanavalin A derivative with reduced valence.", "content": "Concanavalin A (Con A) was labeled with p-azidophenyl alpha-D-mannopyranoside under ultraviolet irradiation and the reaction products were separated by affinity chromatography on Sephadex G-100 at pH 5. One of the Con A derivatives thus obtained was characterized as a monovalent dimer at pH 5 and a divalent tetramer at pH 7 by sedimentation equilibrium and equilibrium dialysis, indicating that this photoaffinity labeling did not alter the quaternary structure of Con A. In agreement with these results, the labeled Con A did not show the capacity to precipitate glycogen at pH 5, but it formed precipitates with glycogen at pH 7. Although its hemagglutinating activity was found to be weaker than that of the native Con A, the dose-response cure of the labeled Con A in the mitogenic stimulation of human peripheral lymphocytes was almost identical to that of the native con A.", "contents": "Photoaffinity labeling of concanavalin A. Preparation of a concanavalin A derivative with reduced valence. Concanavalin A (Con A) was labeled with p-azidophenyl alpha-D-mannopyranoside under ultraviolet irradiation and the reaction products were separated by affinity chromatography on Sephadex G-100 at pH 5. One of the Con A derivatives thus obtained was characterized as a monovalent dimer at pH 5 and a divalent tetramer at pH 7 by sedimentation equilibrium and equilibrium dialysis, indicating that this photoaffinity labeling did not alter the quaternary structure of Con A. In agreement with these results, the labeled Con A did not show the capacity to precipitate glycogen at pH 5, but it formed precipitates with glycogen at pH 7. Although its hemagglutinating activity was found to be weaker than that of the native Con A, the dose-response cure of the labeled Con A in the mitogenic stimulation of human peripheral lymphocytes was almost identical to that of the native con A."}
{"id": "PMID:2590", "title": "Chemical modification of carboxyl groups of fibrinogen and its effect on the binding of cationic detergent.", "content": "Carboxyl groups of native human fibrinogen were modified with glycine methyl ester and 1-ethyl-3(3-dimethylaminopropyl)carbodiimide. It seemed likely that the modification occurred stepwise. Approximately 26% of the carboxyl groups of fibrinogen was modified finally. The modified fibrinogen had no interaction with cationic detergent, and did not form any complex with the detergent. In dilute acid, fibrinogen was observed to show only a slight interaction with cationic detergent. It is probable that the exposed and ionized carboxyl groups are essential for the formation of a complex between fibrinogen and cationic detergent.", "contents": "Chemical modification of carboxyl groups of fibrinogen and its effect on the binding of cationic detergent. Carboxyl groups of native human fibrinogen were modified with glycine methyl ester and 1-ethyl-3(3-dimethylaminopropyl)carbodiimide. It seemed likely that the modification occurred stepwise. Approximately 26% of the carboxyl groups of fibrinogen was modified finally. The modified fibrinogen had no interaction with cationic detergent, and did not form any complex with the detergent. In dilute acid, fibrinogen was observed to show only a slight interaction with cationic detergent. It is probable that the exposed and ionized carboxyl groups are essential for the formation of a complex between fibrinogen and cationic detergent."}
{"id": "PMID:2591", "title": "Purification and characterization of proteinase inhibitors from adzuki beans (Phaseolus angularis).", "content": "Two proteinase inhibitors, designated as inhibitors I and II, were purified from adzuki beans (Phaseolus angularis) by chromatographies on DEAE- and CM-cellulose, and gel filtration on a Sephadex G-100 column. Each inhibitor shows unique inhibitory activities. Inhibitor I was a powerful inhibitor of trypsin [EC 3.4.21.4], but essentially not of chymotrypsin ]EC 3.4.21.1]. On the other hand, inhibitor II inhibited chymotrypsin more strongly than trypsin. The molecular weights estimated from the enzyme inhibition were 3,750 and 9,700 for inhibitors I and II, respectively, assuming that the inhibitions were stoichiometric and in 1 : 1 molar ratio. The amino acid compositions of both inhibitors closely resemble those of low molecular weight inhibitors of other leguminous seeds: they contain large amounts of half-cystine, aspartic acid and serine, and little or no hydrophobic and aromatic amino acids. Inhibitor I lacks both tyrosine and tryptophan residues. The molecular weights were calculated to be 7,894 and 8,620 for inhibitors I and II, respectively. The reliability of these molecular weights was confirmed by the sedimentation equilibrium and 6 M guanidine gel filtration methods. On comparison with the values obtained from enzyme inhibition, it was concluded that inhibitor I and two trypsin inhibitory sites on the molecule, whereas inhibitor II had one chymotrypsin and one trypsin inhibitory sites on the molecule.", "contents": "Purification and characterization of proteinase inhibitors from adzuki beans (Phaseolus angularis). Two proteinase inhibitors, designated as inhibitors I and II, were purified from adzuki beans (Phaseolus angularis) by chromatographies on DEAE- and CM-cellulose, and gel filtration on a Sephadex G-100 column. Each inhibitor shows unique inhibitory activities. Inhibitor I was a powerful inhibitor of trypsin [EC 3.4.21.4], but essentially not of chymotrypsin ]EC 3.4.21.1]. On the other hand, inhibitor II inhibited chymotrypsin more strongly than trypsin. The molecular weights estimated from the enzyme inhibition were 3,750 and 9,700 for inhibitors I and II, respectively, assuming that the inhibitions were stoichiometric and in 1 : 1 molar ratio. The amino acid compositions of both inhibitors closely resemble those of low molecular weight inhibitors of other leguminous seeds: they contain large amounts of half-cystine, aspartic acid and serine, and little or no hydrophobic and aromatic amino acids. Inhibitor I lacks both tyrosine and tryptophan residues. The molecular weights were calculated to be 7,894 and 8,620 for inhibitors I and II, respectively. The reliability of these molecular weights was confirmed by the sedimentation equilibrium and 6 M guanidine gel filtration methods. On comparison with the values obtained from enzyme inhibition, it was concluded that inhibitor I and two trypsin inhibitory sites on the molecule, whereas inhibitor II had one chymotrypsin and one trypsin inhibitory sites on the molecule."}
{"id": "PMID:2592", "title": "Mitochondrial malate dehydrogenase of bovine cerebrum. Characterization and mechanisms of inhibition by silver ions.", "content": "Attempts were made to characterize mitochondrial malate dehydrogenase [L-malate: NAD+ oxidoreductase, EC 1.1.1.37] (M-MDH) purified from bovine cerebrum and to elucidate the mechanisms responsible for inhibition of the enzymic activity by Ag+. The molecular weights of the native enzyme and its subunits were 54,000-55,000 and 30,000-32,000, respectively. In general, the physiochemical and catalytic properties of bovine cerebral M-MDH was not very different from those of other corresponding mammalian enzymes. Incubation of the enzyme with Ag+ caused the loss of equivalent amounts of sulfhydryls with a parallel decrease of the enzymic activity. When the enzyme was exposed to 2-, 3.5-, and 5-fold molar excesses of Ag+, the enzymic activity showed an initial rapid fall and a subsequent slow restoration to a partially inactivated level (60-70, 45-50, and 15-20% of an untreated control, respectively), while the alpha-helical content of the enzyme fell exponentially with time. A 7-fold molar excess of Ag+ reduced both the enzymic activity and the alpha-helical content to a much greater degree and no restoration of the enzymic activity was observed. The Km values of Ag+-inactivated enzyme for NADH and oxaloacetate were the same as those of the native enzyme. The data suggest that Ag+ could inhibit enzymic activity both by reducing the structural regularity of the enzyme molecule and by attacking sulfhydryl groups necessary for the catalytic activity of bovine cerebral M-MDH.", "contents": "Mitochondrial malate dehydrogenase of bovine cerebrum. Characterization and mechanisms of inhibition by silver ions. Attempts were made to characterize mitochondrial malate dehydrogenase [L-malate: NAD+ oxidoreductase, EC 1.1.1.37] (M-MDH) purified from bovine cerebrum and to elucidate the mechanisms responsible for inhibition of the enzymic activity by Ag+. The molecular weights of the native enzyme and its subunits were 54,000-55,000 and 30,000-32,000, respectively. In general, the physiochemical and catalytic properties of bovine cerebral M-MDH was not very different from those of other corresponding mammalian enzymes. Incubation of the enzyme with Ag+ caused the loss of equivalent amounts of sulfhydryls with a parallel decrease of the enzymic activity. When the enzyme was exposed to 2-, 3.5-, and 5-fold molar excesses of Ag+, the enzymic activity showed an initial rapid fall and a subsequent slow restoration to a partially inactivated level (60-70, 45-50, and 15-20% of an untreated control, respectively), while the alpha-helical content of the enzyme fell exponentially with time. A 7-fold molar excess of Ag+ reduced both the enzymic activity and the alpha-helical content to a much greater degree and no restoration of the enzymic activity was observed. The Km values of Ag+-inactivated enzyme for NADH and oxaloacetate were the same as those of the native enzyme. The data suggest that Ag+ could inhibit enzymic activity both by reducing the structural regularity of the enzyme molecule and by attacking sulfhydryl groups necessary for the catalytic activity of bovine cerebral M-MDH."}
{"id": "PMID:2593", "title": "Double-headed protease inhibitors from black-eyed peas. II. Structural studies by optical absorption and circular dichroism.", "content": "Two new double-headed protease inhibitors from black-eyed peas have amino acid compositions typical of the low molecular weight protease inhibitors from legume seeds. Black-eyed pea chymotrypsin and trypsin inhibitor (BEPCI) contains no tryptophan, 1 tyrosine, and 14 half-cystines out of 83 amino acid residues per monomer. Black-eyed pea trypsin inhibitor (BEPTI) contains no tryptophan, 1 tyrosine, and 14 half-cystines out of 75 residues per monomer. The molar extinctions at 280 nm are 2770 for BEPCI and 3440 for BEPTI. The single tyrosyl residue is very inaccessible to solvent in native BEPCI and BEPTI at neutral pH and titrates anomalously with an apparent pK = 12. Ionization of tyrosine is complete in 13 hours above pH 12. No heterogeneity of the local environment of the tyrosyl residues in different subunits can be detected spectrophotometrically. The large number of cystine residues leads to an intense and complex near-ultraviolet CD spectrum with cystine contributions in the regions of 248 and 280 nm and tyrosine contributions at 233 and 280 nm. An intact disulfide structure is required for appearance of the tyrosyl CD bands. The inhibitors are unusually resistant to denaturation when compared with similar low molecular weight proteins of high disulfide content. All observations are consistent with a far more rigid structure for BEPCI and BEPTI than for a typical protein.", "contents": "Double-headed protease inhibitors from black-eyed peas. II. Structural studies by optical absorption and circular dichroism. Two new double-headed protease inhibitors from black-eyed peas have amino acid compositions typical of the low molecular weight protease inhibitors from legume seeds. Black-eyed pea chymotrypsin and trypsin inhibitor (BEPCI) contains no tryptophan, 1 tyrosine, and 14 half-cystines out of 83 amino acid residues per monomer. Black-eyed pea trypsin inhibitor (BEPTI) contains no tryptophan, 1 tyrosine, and 14 half-cystines out of 75 residues per monomer. The molar extinctions at 280 nm are 2770 for BEPCI and 3440 for BEPTI. The single tyrosyl residue is very inaccessible to solvent in native BEPCI and BEPTI at neutral pH and titrates anomalously with an apparent pK = 12. Ionization of tyrosine is complete in 13 hours above pH 12. No heterogeneity of the local environment of the tyrosyl residues in different subunits can be detected spectrophotometrically. The large number of cystine residues leads to an intense and complex near-ultraviolet CD spectrum with cystine contributions in the regions of 248 and 280 nm and tyrosine contributions at 233 and 280 nm. An intact disulfide structure is required for appearance of the tyrosyl CD bands. The inhibitors are unusually resistant to denaturation when compared with similar low molecular weight proteins of high disulfide content. All observations are consistent with a far more rigid structure for BEPCI and BEPTI than for a typical protein."}
{"id": "PMID:2594", "title": "Double-headed protease inhibitors from black-eyed peas. III. Subunit interactions of the native and half-site chemically modified proteins.", "content": "The chemical modification of two new double-headed-protease inhibitors from black-eyed peas, a trypsin-chymotrypsin inhibitor (BEPCI) and a trypsin inhibitor (BEPTI) with dansyl chloride was investigated under various conditions. The NH2-terminal serine of both BEPCI and BEPTI, the 4 lysyl residues of BEPCI, and 4 of the 5 lysyl residues of BEPTI, could not be dansylated in the absence of urea. The single tyrosine per subunit of BEPCI and BEPTI was unreactive even in the presence of urea but could be labeled with half-site reactivity by the Celite method. Lysine, NH2-terminal serine, and tyrosine were reactive in fully reduced, carbamidomethylated BEPCI and BEPTI. Gel filtration was used to study the subunit interactions of BEPCI and BEPTI. At pH 8 or pH 3.0 there is a complex set of multiple equilibria with widely differing rates of attainment. We have found evidence for a rapid dimer-tetramer equilibrium, a distinct moderate rate dimer-tetramer equilibrium, a very slow monomer-dimer equilibrium, and postulate slow isomerization of the two forms of dimer and the two forms of tetramer. The monomer-dimer equilibrium is quite unusual in that the dimer is stabilized by chaotropic ions and even slightly by guanidine HC1. In contrast to the complex pattern seen in native BEPCI, the half-site, dansylated BEPCI exists at similar concentration exclusively as a tetramer at neutral pH.", "contents": "Double-headed protease inhibitors from black-eyed peas. III. Subunit interactions of the native and half-site chemically modified proteins. The chemical modification of two new double-headed-protease inhibitors from black-eyed peas, a trypsin-chymotrypsin inhibitor (BEPCI) and a trypsin inhibitor (BEPTI) with dansyl chloride was investigated under various conditions. The NH2-terminal serine of both BEPCI and BEPTI, the 4 lysyl residues of BEPCI, and 4 of the 5 lysyl residues of BEPTI, could not be dansylated in the absence of urea. The single tyrosine per subunit of BEPCI and BEPTI was unreactive even in the presence of urea but could be labeled with half-site reactivity by the Celite method. Lysine, NH2-terminal serine, and tyrosine were reactive in fully reduced, carbamidomethylated BEPCI and BEPTI. Gel filtration was used to study the subunit interactions of BEPCI and BEPTI. At pH 8 or pH 3.0 there is a complex set of multiple equilibria with widely differing rates of attainment. We have found evidence for a rapid dimer-tetramer equilibrium, a distinct moderate rate dimer-tetramer equilibrium, a very slow monomer-dimer equilibrium, and postulate slow isomerization of the two forms of dimer and the two forms of tetramer. The monomer-dimer equilibrium is quite unusual in that the dimer is stabilized by chaotropic ions and even slightly by guanidine HC1. In contrast to the complex pattern seen in native BEPCI, the half-site, dansylated BEPCI exists at similar concentration exclusively as a tetramer at neutral pH."}
{"id": "PMID:2595", "title": "Affinity labeling of the primary bilirubin binding site of human serum albumin.", "content": "A label for the bilirubin binding sites of human serum albumin was synthesized by reacting 2 mol of Woodward's reagent K (N-ethyl-5-phenylisoxazolium-3'-sulfonate) with 1 mol of bilirubin. This yielded a water-soluble derivative in which both carboxyl groups of bilirubin were converted to reactive enol esters. Covalent labeling was achieved by reacting the label with human serum albumin under nitrogen at pH 9.4 and 20 degrees. Under the same conditions, no covalent binding to the monomers of several proteins could be demonstrated. The number of binding sites for bilirubin and the label were found to be the same, and competition experiments with bilirubin showed inhibition of covalent labeling. The absorption, fluorescence and CD spectra of the label in a complex with human serum albumin were similar to those of the bilirubin human serum albumin complex. However, following covalent attachment to the spectral properties were changed, indicating loss of conformational freedom of the chromophore. Labeling ratios were selected to result in the incorporation of less than 1 mol of label/mol of human serum albumin. Under these conditions, labeling is thought to occur primarily at the high affinity binding site.", "contents": "Affinity labeling of the primary bilirubin binding site of human serum albumin. A label for the bilirubin binding sites of human serum albumin was synthesized by reacting 2 mol of Woodward's reagent K (N-ethyl-5-phenylisoxazolium-3'-sulfonate) with 1 mol of bilirubin. This yielded a water-soluble derivative in which both carboxyl groups of bilirubin were converted to reactive enol esters. Covalent labeling was achieved by reacting the label with human serum albumin under nitrogen at pH 9.4 and 20 degrees. Under the same conditions, no covalent binding to the monomers of several proteins could be demonstrated. The number of binding sites for bilirubin and the label were found to be the same, and competition experiments with bilirubin showed inhibition of covalent labeling. The absorption, fluorescence and CD spectra of the label in a complex with human serum albumin were similar to those of the bilirubin human serum albumin complex. However, following covalent attachment to the spectral properties were changed, indicating loss of conformational freedom of the chromophore. Labeling ratios were selected to result in the incorporation of less than 1 mol of label/mol of human serum albumin. Under these conditions, labeling is thought to occur primarily at the high affinity binding site."}
{"id": "PMID:2596", "title": "Acylation of subtilisin Carlsberg by phenyl esters.", "content": "Approximate Hammett reaction constants rho calculated from k2/K8 values of several phenyl esters of N-acetyl-L-phenylalanine, hippuric acid, and beta-phenylpropionic acid are 0.0, 0.4, and 1.0 respectively. To determine whether the lack of substituent effect of k2/K8 with the N-acetyl-L-phenylalanine esters is a result of substituent-insensitive k2 or rate-limiting association of enzyme and substrate, pH-k2/K8 deependences and solvent deuterium isotope effects were determined for certain of the substrates and compared with those found with the corresponding hippurates and beta-phenylpropionates. In the pH range 5 to 8, k2/K8 of the phenyl and 4-nitrophenyl esters of each series is dependent upon the unprotonated form of an enzymatic base of apparent pKa approximately 7.4, identical with the pKa found for the free enzyme. With the phenyl esters of each substrate class, k2/K8 decreased by 2 to 3 times in deuterium oxide compared with water. The results suggest that a step involving a general base-catalyzed proton transfer, almost certainly k2, is rate-limiting with the N-acetyl-L-phenylalaninates, as well as the hippurates and beta-phenylpropionates. Attack by the protein on the latter substrates is prediminantly nucleophilic, judged by the similarity of rho in the enzymatic and reference hydroxide ion-catalyzed hydrolyses. The power rho values for the N-acetyl-L-phenylalaninates and hippurates could result from an electrophilic component in their hydrolytic mechanisms.", "contents": "Acylation of subtilisin Carlsberg by phenyl esters. Approximate Hammett reaction constants rho calculated from k2/K8 values of several phenyl esters of N-acetyl-L-phenylalanine, hippuric acid, and beta-phenylpropionic acid are 0.0, 0.4, and 1.0 respectively. To determine whether the lack of substituent effect of k2/K8 with the N-acetyl-L-phenylalanine esters is a result of substituent-insensitive k2 or rate-limiting association of enzyme and substrate, pH-k2/K8 deependences and solvent deuterium isotope effects were determined for certain of the substrates and compared with those found with the corresponding hippurates and beta-phenylpropionates. In the pH range 5 to 8, k2/K8 of the phenyl and 4-nitrophenyl esters of each series is dependent upon the unprotonated form of an enzymatic base of apparent pKa approximately 7.4, identical with the pKa found for the free enzyme. With the phenyl esters of each substrate class, k2/K8 decreased by 2 to 3 times in deuterium oxide compared with water. The results suggest that a step involving a general base-catalyzed proton transfer, almost certainly k2, is rate-limiting with the N-acetyl-L-phenylalaninates, as well as the hippurates and beta-phenylpropionates. Attack by the protein on the latter substrates is prediminantly nucleophilic, judged by the similarity of rho in the enzymatic and reference hydroxide ion-catalyzed hydrolyses. The power rho values for the N-acetyl-L-phenylalaninates and hippurates could result from an electrophilic component in their hydrolytic mechanisms."}
{"id": "PMID:2597", "title": "Inhibition by superoxide dismutase of methemoglobin formation from oxyhemoglobin.", "content": "The formation of methemoglobin from oxyhemoglobin in a solution containing photoreduced riboflavin and oxygen was inhibited by superoxide dismutase. The rate of the reaction was pH-dependent in the range of 6.8 to 7.8, increasing as the pH was reduced. Inhibition by superoxide dismutase was enhanced as the EDTA concentration increased and was dependent on enzymatic activity. Under conditions in which superoxide dismutase inhibition was incomplete, catalase inhibited the reaction but mannitol had no effect. The data support the mediation of methemoglobin formation by superoxide. The hypothesis is offered that superoxide anion reduced the heme-bound oxygen in oxygemoglobin by one electron, permitting the subsequent dissociation of ferrihemoglobin and peroxide. The ability of superoxide dismutase to inhibit the formation of methemoglobin may represent one of its functions in the mature erythrocyte.", "contents": "Inhibition by superoxide dismutase of methemoglobin formation from oxyhemoglobin. The formation of methemoglobin from oxyhemoglobin in a solution containing photoreduced riboflavin and oxygen was inhibited by superoxide dismutase. The rate of the reaction was pH-dependent in the range of 6.8 to 7.8, increasing as the pH was reduced. Inhibition by superoxide dismutase was enhanced as the EDTA concentration increased and was dependent on enzymatic activity. Under conditions in which superoxide dismutase inhibition was incomplete, catalase inhibited the reaction but mannitol had no effect. The data support the mediation of methemoglobin formation by superoxide. The hypothesis is offered that superoxide anion reduced the heme-bound oxygen in oxygemoglobin by one electron, permitting the subsequent dissociation of ferrihemoglobin and peroxide. The ability of superoxide dismutase to inhibit the formation of methemoglobin may represent one of its functions in the mature erythrocyte."}
{"id": "PMID:2598", "title": "Transport and metabolism of vitamin B6 in the yeast Saccharomyces carlsbergensis 4228.", "content": "Active transport of pyridoxine, pyridoxal, and pyridoxamine occurs in resting cells of Saccharomyces carlsbergensis 4228 and can lead to intracellular concentrations of free vitamin much higher than those supplied externally. The initial Km for pyridoxine uptake is 3.6 x 10(-7) M at 30 degrees and pH 4.5, which are optimum for growth. Transport is inhibited by many unphosphorylated vitamin analogs, the most effective being 5'-deoxypyridoxine, 5'-deoxypridoxal, toxopyrimidine, 4'-deoxypyridoxine, and 3-amino-3-deoxypyridoxine. Two distinct uptake systems that differ in structural specificity and ionic requirements are present. One, with optimum pH of 3.5, transports pyridoxal effectively, but not pyridoxamine; the other (optimum pH 6.0) transports pyridoxamine effectively, but not pyridoxal. Both systems transport pyridoxine, while neither transports pyridoxal 5'-phosphate. Other properties of these systems are similar, indicating that they share certain elements in common. An initial temperature optimum of 30 degrees is observed for pyrodoxine transport and, at this temperature, an \"overshoot\" in intracellular vitamin levels, with subsequent decrease to a constant level, occurs with time. It appears that intracellular vitamin, or a derivative, activates the exit mechanism for the vitamin. Exit rates also depend on the resuspension buffer and are increased in the presence of glucose and decreased by azide. Above 30 degrees net uptake of pyridoxine drops initially, then rapidly increases to a second optimum at 50 degrees; the uptake system is inactivated at about 55 degrees. The optimum at 50 degrees apparently results from activation of inflow as exit is rapid and is accelerated by azide. No overshoot was detected at 50 degrees, so it appears that the exit system is not regulated by intracellular vitamin at this temperature. A phase transition in membrane lipids occurs at 30 degrees and may be responsible for the change in properties of the inflow and exit mechanisms above this temperature.", "contents": "Transport and metabolism of vitamin B6 in the yeast Saccharomyces carlsbergensis 4228. Active transport of pyridoxine, pyridoxal, and pyridoxamine occurs in resting cells of Saccharomyces carlsbergensis 4228 and can lead to intracellular concentrations of free vitamin much higher than those supplied externally. The initial Km for pyridoxine uptake is 3.6 x 10(-7) M at 30 degrees and pH 4.5, which are optimum for growth. Transport is inhibited by many unphosphorylated vitamin analogs, the most effective being 5'-deoxypyridoxine, 5'-deoxypridoxal, toxopyrimidine, 4'-deoxypyridoxine, and 3-amino-3-deoxypyridoxine. Two distinct uptake systems that differ in structural specificity and ionic requirements are present. One, with optimum pH of 3.5, transports pyridoxal effectively, but not pyridoxamine; the other (optimum pH 6.0) transports pyridoxamine effectively, but not pyridoxal. Both systems transport pyridoxine, while neither transports pyridoxal 5'-phosphate. Other properties of these systems are similar, indicating that they share certain elements in common. An initial temperature optimum of 30 degrees is observed for pyrodoxine transport and, at this temperature, an \"overshoot\" in intracellular vitamin levels, with subsequent decrease to a constant level, occurs with time. It appears that intracellular vitamin, or a derivative, activates the exit mechanism for the vitamin. Exit rates also depend on the resuspension buffer and are increased in the presence of glucose and decreased by azide. Above 30 degrees net uptake of pyridoxine drops initially, then rapidly increases to a second optimum at 50 degrees; the uptake system is inactivated at about 55 degrees. The optimum at 50 degrees apparently results from activation of inflow as exit is rapid and is accelerated by azide. No overshoot was detected at 50 degrees, so it appears that the exit system is not regulated by intracellular vitamin at this temperature. A phase transition in membrane lipids occurs at 30 degrees and may be responsible for the change in properties of the inflow and exit mechanisms above this temperature."}
{"id": "PMID:2599", "title": "Transport and metabolism of vitamin B6 in Salmonella typhimurium LT2.", "content": "Salmonella typhimurium LT2 concentrates radioactivity intracellularly from [3H]pyridoxal or [3H]pyridoxine up to 25 times the external concentration. After 1 min of uptake intracellular radioactivity is found as phosphorylated vitamin B6. The process is sensitive to temperature and is maximally active at pH 8.1, but under the conditions tested it is insensitive to monovalent cations or metabolic inhibitors, and does not require an exogenous energy source. The Km values for uptake of pyridoxine and pyridoxal are 2.0 x 10(-7) M and 1.2 x 10(-7) M, respectively; [3H]pyridoxamine is not transported. Evidence is presented for an uptake mechanism involving facilitated diffusion followed by trapping by pyridoxal kinase. S. typhimurium also appears to lack a periplasmic binding protein for vitamin B6.", "contents": "Transport and metabolism of vitamin B6 in Salmonella typhimurium LT2. Salmonella typhimurium LT2 concentrates radioactivity intracellularly from [3H]pyridoxal or [3H]pyridoxine up to 25 times the external concentration. After 1 min of uptake intracellular radioactivity is found as phosphorylated vitamin B6. The process is sensitive to temperature and is maximally active at pH 8.1, but under the conditions tested it is insensitive to monovalent cations or metabolic inhibitors, and does not require an exogenous energy source. The Km values for uptake of pyridoxine and pyridoxal are 2.0 x 10(-7) M and 1.2 x 10(-7) M, respectively; [3H]pyridoxamine is not transported. Evidence is presented for an uptake mechanism involving facilitated diffusion followed by trapping by pyridoxal kinase. S. typhimurium also appears to lack a periplasmic binding protein for vitamin B6."}
{"id": "PMID:2600", "title": "Correlation of the kinetics of electron transfer activity of various eukaryotic cytochromes c with binding to mitochondrial cytochrome c oxidase.", "content": "1. A detailed study of cytochrome c oxidase activity with Keilin-Hartree particles and purified beef heart enzyme, at low ionic strength and low cytochrome c concentrations, showed biphasic kinetics with apparent Km1 = 5 x 10(-8) M, and apparent Km2 = 0.35 to 1.0 x 10(-6) M. Direct binding studies with purified oxidase, phospholipid-containing as well as phospholiptaining aid-depleted, demonstrated two sites of interaction of cytochrome c with the enzyme, with KD1  less than or equal to 10(-7) M, and KD2 = 10(-6) M. 2. The maximal velocities as low ionic strength increased with pH and were highest above ph 7.5. 3. The presence and properties of the low apparent Km phase of the kinetics were strongly dependent on the nature and concentration of the anions in the medium. The multivalent anions, phosphate, ADP, and ATP, greatly decreased the proportion of this phase and similarly decreased the amount of high affinity cytochrome c-cytochrome oxidase complex formed. The order of effectiveness was ATP greater than ADP greater than P1 and since phosphate binds to cytochrome c more strongly than the nucleotides, it is concluded that the inhibition resulted from anion interaction with the oxidase. 4mat low concentrations bakers' yeast iso-1, bakers' yeast iso-1, horse, and Euglena cytochromes c at high concentrations all attained the same maximal velocity. The different proportions of low apparent Km phase in the kinetic patterns of these cytochromes c correlated with the amounts of high affinity complex formed with purified cytochrome c oxidase. 5. The apparent Km for cytochrome c activity in the succinate-cytochrome c reductase system of Keilin-Hartree particles was identical with that obtained with the oxidase (5 x 10(-8) M), suggesting the same site serves both reactions. 6. It is concluded that the observed kinetics result from two catalytically active sites on the cytochrome c oxidase protein of different affinities for cytochrome c. The high affinity binding of cytochrome c to the mitochondrial membrane is provided by the oxidase and at this site cytochrome c can be reduced by cytochrome c1. Physiological concentrations of ATP decrease the affinity of this binding to the point that interaction of cytochrome c with numerous mitochondrial pholpholipid sites can competitively remove cytochrome c from the oxidase. It is suggested that this effect of ATP represents a possible mechanism for the control of electron flow to the oxidase.", "contents": "Correlation of the kinetics of electron transfer activity of various eukaryotic cytochromes c with binding to mitochondrial cytochrome c oxidase. 1. A detailed study of cytochrome c oxidase activity with Keilin-Hartree particles and purified beef heart enzyme, at low ionic strength and low cytochrome c concentrations, showed biphasic kinetics with apparent Km1 = 5 x 10(-8) M, and apparent Km2 = 0.35 to 1.0 x 10(-6) M. Direct binding studies with purified oxidase, phospholipid-containing as well as phospholiptaining aid-depleted, demonstrated two sites of interaction of cytochrome c with the enzyme, with KD1  less than or equal to 10(-7) M, and KD2 = 10(-6) M. 2. The maximal velocities as low ionic strength increased with pH and were highest above ph 7.5. 3. The presence and properties of the low apparent Km phase of the kinetics were strongly dependent on the nature and concentration of the anions in the medium. The multivalent anions, phosphate, ADP, and ATP, greatly decreased the proportion of this phase and similarly decreased the amount of high affinity cytochrome c-cytochrome oxidase complex formed. The order of effectiveness was ATP greater than ADP greater than P1 and since phosphate binds to cytochrome c more strongly than the nucleotides, it is concluded that the inhibition resulted from anion interaction with the oxidase. 4mat low concentrations bakers' yeast iso-1, bakers' yeast iso-1, horse, and Euglena cytochromes c at high concentrations all attained the same maximal velocity. The different proportions of low apparent Km phase in the kinetic patterns of these cytochromes c correlated with the amounts of high affinity complex formed with purified cytochrome c oxidase. 5. The apparent Km for cytochrome c activity in the succinate-cytochrome c reductase system of Keilin-Hartree particles was identical with that obtained with the oxidase (5 x 10(-8) M), suggesting the same site serves both reactions. 6. It is concluded that the observed kinetics result from two catalytically active sites on the cytochrome c oxidase protein of different affinities for cytochrome c. The high affinity binding of cytochrome c to the mitochondrial membrane is provided by the oxidase and at this site cytochrome c can be reduced by cytochrome c1. Physiological concentrations of ATP decrease the affinity of this binding to the point that interaction of cytochrome c with numerous mitochondrial pholpholipid sites can competitively remove cytochrome c from the oxidase. It is suggested that this effect of ATP represents a possible mechanism for the control of electron flow to the oxidase."}
{"id": "PMID:2601", "title": "Autooxidation and hydroxylation reactions of oxygenated cytochrome P-450cam.", "content": "Oxy-ferrous substrate-bound cytochrome P-450cam (mrsO2) autooxidizes in the absence of its specific effector protein, putidaredoxin, without hydroxylating the substrate, camphor. The autooxidation is first order with an activation energy of 17 kcal mol-1 at 25 degrees, pH 7.0. Substrate removal and low pH accelerate the reaction. The product, 5-exo-OH camphor, and a nonhydroxylated pseudosubstrate, norcamphor, stabilize the complex in a manner similar to camphor. Increased oxidation rate of mrsO2 and substrate hydroxylation are induced by putidaredoxin, rebredoxin, cytochrome b5, and the apoproteins of the latter two. Dihydrolipoic acid and other dithiols also replace putidaredoxin as effector molecules, but 1000-fold higher concentrations are required. Effector molecules do not increase the autooxidation rate of mrsO2 unless camphor, norcamphor, or another pseudosubstrate is present. Kinetic evidence is presented showing that an active complex between mrsO2 and effector is a required intermediate in mixed function oxidation.", "contents": "Autooxidation and hydroxylation reactions of oxygenated cytochrome P-450cam. Oxy-ferrous substrate-bound cytochrome P-450cam (mrsO2) autooxidizes in the absence of its specific effector protein, putidaredoxin, without hydroxylating the substrate, camphor. The autooxidation is first order with an activation energy of 17 kcal mol-1 at 25 degrees, pH 7.0. Substrate removal and low pH accelerate the reaction. The product, 5-exo-OH camphor, and a nonhydroxylated pseudosubstrate, norcamphor, stabilize the complex in a manner similar to camphor. Increased oxidation rate of mrsO2 and substrate hydroxylation are induced by putidaredoxin, rebredoxin, cytochrome b5, and the apoproteins of the latter two. Dihydrolipoic acid and other dithiols also replace putidaredoxin as effector molecules, but 1000-fold higher concentrations are required. Effector molecules do not increase the autooxidation rate of mrsO2 unless camphor, norcamphor, or another pseudosubstrate is present. Kinetic evidence is presented showing that an active complex between mrsO2 and effector is a required intermediate in mixed function oxidation."}
{"id": "PMID:2602", "title": "Demonstration of a precursor-product relationship between soluble and cross-linked elastin, and the biosynthesis of the desmosines in vitro.", "content": "Direct evidence showing that a soluble form of elastin is the precursor of cross-linked elastin was obtained from pulse-chase experiments using chick embryo aortas and by demonstrating the conversion of soluble elastin into cross-linked elastin in a cell-free system. Acetic acid extracts of embryonic chick aorta pulse-labeled with [14C]lysine contain two radioactive proteins of molecular weights 74,000 and 138,000 which have been identified previously as soluble elastin and the pro-alpha chain of collagen, respectively. In pulse-chase experiments, the radioactivity incorporated in the soluble elastin during the pulse with [14C]lysine disappeared during a 24-hour chase with [12C]lysine and 89% of that which disappeared was accounted for in the desmosines of alkali-insoluble elastin. The disappearance of the radioactivity from the soluble fraction and its appearance in the desmosines of elastin were inhibited by beta-aminopropionitrile, a specific inhibitor of the cross-linking enzyme lysyl oxidase. In addition in vitro experiments, it was shown that the radioactivity in the desmosines of elastin can arise from that present in an acid-soluble precursor protein. This precursor protein is soluble elastin, as demonstrated by the formation of desmosines when a homogeneous preparation of soluble elastin was incubated with purified lysyl oxidase.", "contents": "Demonstration of a precursor-product relationship between soluble and cross-linked elastin, and the biosynthesis of the desmosines in vitro. Direct evidence showing that a soluble form of elastin is the precursor of cross-linked elastin was obtained from pulse-chase experiments using chick embryo aortas and by demonstrating the conversion of soluble elastin into cross-linked elastin in a cell-free system. Acetic acid extracts of embryonic chick aorta pulse-labeled with [14C]lysine contain two radioactive proteins of molecular weights 74,000 and 138,000 which have been identified previously as soluble elastin and the pro-alpha chain of collagen, respectively. In pulse-chase experiments, the radioactivity incorporated in the soluble elastin during the pulse with [14C]lysine disappeared during a 24-hour chase with [12C]lysine and 89% of that which disappeared was accounted for in the desmosines of alkali-insoluble elastin. The disappearance of the radioactivity from the soluble fraction and its appearance in the desmosines of elastin were inhibited by beta-aminopropionitrile, a specific inhibitor of the cross-linking enzyme lysyl oxidase. In addition in vitro experiments, it was shown that the radioactivity in the desmosines of elastin can arise from that present in an acid-soluble precursor protein. This precursor protein is soluble elastin, as demonstrated by the formation of desmosines when a homogeneous preparation of soluble elastin was incubated with purified lysyl oxidase."}
{"id": "PMID:2603", "title": "Chondroitinase C from Flavobacterium heparinum.", "content": "A chondroitinase that acts upon chondroitin sulfate C and hyaluronic acid was isolated from Flavobacterium heparinum. This enzyme was seperated from constitutional chondroitinase AC and an induced chondroitinase B also present in extracts of F. heparinum previously grown in the presence of chondroitin sulfates A, B or C. The enzyme acts upon chondroitin sulfate C producing tetrasaccharide plus an unsaturated 6-sulfated disaccharide (delta Di-6S), and upon hyaluronic acid producing unsaturated nonsulfated disaccharide (delta Di-OS). Chondroitin sulfate A is also degraded producing oligosaccharides and delta Di-6S but not delta Di-4S. The chondroitinase C is also distinguished from the chondroitinases B and AC by several properties, such as effect of ions, temperature for optimal activity, and susceptibility to increasing salt concentrations. The substrate specificity of the chondroitinase C is different from that of any other chondroitinase or hyaluronidase described so far.", "contents": "Chondroitinase C from Flavobacterium heparinum. A chondroitinase that acts upon chondroitin sulfate C and hyaluronic acid was isolated from Flavobacterium heparinum. This enzyme was seperated from constitutional chondroitinase AC and an induced chondroitinase B also present in extracts of F. heparinum previously grown in the presence of chondroitin sulfates A, B or C. The enzyme acts upon chondroitin sulfate C producing tetrasaccharide plus an unsaturated 6-sulfated disaccharide (delta Di-6S), and upon hyaluronic acid producing unsaturated nonsulfated disaccharide (delta Di-OS). Chondroitin sulfate A is also degraded producing oligosaccharides and delta Di-6S but not delta Di-4S. The chondroitinase C is also distinguished from the chondroitinases B and AC by several properties, such as effect of ions, temperature for optimal activity, and susceptibility to increasing salt concentrations. The substrate specificity of the chondroitinase C is different from that of any other chondroitinase or hyaluronidase described so far."}
{"id": "PMID:2604", "title": "Transport mechanisms in isolated plasma membranes. Nucleoside processing by membrane vesicles from mouse fibroblast cells grown in defined medium.", "content": "Plasma membrane vesicles were isolated from a subline of L929 mouse fibroblasts grown on defined medium in the absence of serum. These vesicles were not significantly contaminated by mitochondria or endoplasmic reticulum. The isolation procedure, a modification of that originally developed by McKeel and Jarett (McKeel, D.W., and Jarett, L. (1970) J. Cell Biol. 44, 417-432) employs mechanical homogenization in isotonic medium followed by differential centrifugation. The resultant plasma membrane vesicles take up radioactivity when exposed to uniformly labeled nucleosides. Two subfractions of the plasma membrane were isolated, distinguished by their differing activity of 5'-nucleotidase and (Na+,K+)-stimulated ATPase, two well known plasma membrane enzyme markers. Uptake of nucleoside radioactivity was extensively studied in one subfraction; it was linear with time and membrane concentration over ranges used for the studies. Apparent Km values for uptake of radioactivity from adenosine, inosine, and uridine were 7.1 +/- 26 muM, respectively. Uptake of radioactivity from all three nucleosides exhibits a broad pH optimum from pH 7 to pH 9, but falls off rapidly at lower pH. N-Ethylmaleimide was an effective inhibitor of uptake of radioactivity from all three nucleosides; uptake of radioactivity from uridine is more sensitive than uptake of radioactivity from the purine nucleosides. Adenosine inhibited uptake of radioactivity from inosine more than from uridine. Inosine inhibited the uptake of radioactivity from adenosine, but uridine did not. Caffeine and 6-methylaminopurine riboside (6-N-methyladenosine differentially inhibit uptake of radioactivity from adenosine and inosine, and thus the vesicles apparently possess seperate transport systems for uptake of radioactivity from purine nucleosides and from uridine.", "contents": "Transport mechanisms in isolated plasma membranes. Nucleoside processing by membrane vesicles from mouse fibroblast cells grown in defined medium. Plasma membrane vesicles were isolated from a subline of L929 mouse fibroblasts grown on defined medium in the absence of serum. These vesicles were not significantly contaminated by mitochondria or endoplasmic reticulum. The isolation procedure, a modification of that originally developed by McKeel and Jarett (McKeel, D.W., and Jarett, L. (1970) J. Cell Biol. 44, 417-432) employs mechanical homogenization in isotonic medium followed by differential centrifugation. The resultant plasma membrane vesicles take up radioactivity when exposed to uniformly labeled nucleosides. Two subfractions of the plasma membrane were isolated, distinguished by their differing activity of 5'-nucleotidase and (Na+,K+)-stimulated ATPase, two well known plasma membrane enzyme markers. Uptake of nucleoside radioactivity was extensively studied in one subfraction; it was linear with time and membrane concentration over ranges used for the studies. Apparent Km values for uptake of radioactivity from adenosine, inosine, and uridine were 7.1 +/- 26 muM, respectively. Uptake of radioactivity from all three nucleosides exhibits a broad pH optimum from pH 7 to pH 9, but falls off rapidly at lower pH. N-Ethylmaleimide was an effective inhibitor of uptake of radioactivity from all three nucleosides; uptake of radioactivity from uridine is more sensitive than uptake of radioactivity from the purine nucleosides. Adenosine inhibited uptake of radioactivity from inosine more than from uridine. Inosine inhibited the uptake of radioactivity from adenosine, but uridine did not. Caffeine and 6-methylaminopurine riboside (6-N-methyladenosine differentially inhibit uptake of radioactivity from adenosine and inosine, and thus the vesicles apparently possess seperate transport systems for uptake of radioactivity from purine nucleosides and from uridine."}
{"id": "PMID:2605", "title": "Metallophosphoryl and Apophosphoryl Alkaline Phosphatases.", "content": "The noncovalent phosphate (E-P) and covalent phosphory (E-P) complexes of Zn(II), Cd(II), and apoalkaline phosphatases of Escherichia coli have been studied by stopped flow kinetic methods and 32P-labeling techniques. With 2,4-dinitrophenylphosphate as substrate, preincubation of the Zn(II) enzyme with Pi at pH 8 slows the pre-steady state burst rate, but does not affect the burst magnitude of 1 mol of ROH per enzyme dimer. Preincubation of the enzyme with Pi at pH 5.5 reduces the burst magnitude by one-half, as well as reducing the burst rate. Reduction of the burst magnitude as a function of the pH of the preincubation with Pi follows the same function as that previously established for the formation of E-P. Hence, ROP phosphorylates the enzyme by displacing phosphate from E-P during a pre-steady state reaction, while E-P turns over at the steady state velocity.", "contents": "Metallophosphoryl and Apophosphoryl Alkaline Phosphatases. The noncovalent phosphate (E-P) and covalent phosphory (E-P) complexes of Zn(II), Cd(II), and apoalkaline phosphatases of Escherichia coli have been studied by stopped flow kinetic methods and 32P-labeling techniques. With 2,4-dinitrophenylphosphate as substrate, preincubation of the Zn(II) enzyme with Pi at pH 8 slows the pre-steady state burst rate, but does not affect the burst magnitude of 1 mol of ROH per enzyme dimer. Preincubation of the enzyme with Pi at pH 5.5 reduces the burst magnitude by one-half, as well as reducing the burst rate. Reduction of the burst magnitude as a function of the pH of the preincubation with Pi follows the same function as that previously established for the formation of E-P. Hence, ROP phosphorylates the enzyme by displacing phosphate from E-P during a pre-steady state reaction, while E-P turns over at the steady state velocity."}
{"id": "PMID:2606", "title": "31P NMR of phosphate and phosphonate complexes of metalloalkaline phosphatases.", "content": "31P NMR spectra of phosphate and phosphonate complexes of Escherichia coli alkaline phosphatase have been obtained by Fourier transform NMR methods. One equivalent of P1i, bound to Zn(II) alkaline phosphatase, pH 8, gives rise to a single 31P resonance 2 ppm downfield from that for Pi, and assignable to the noncovalent complex, E-P. Inorganic phosphate in excess of 1 eq per enzyme dimer gives rise to a resonance at the position expected for free Pi. At pH 5.1, a second resonance appears 8.5 ppm downfield from that for free Pi, and is assignable to the covalent complex, E-P. The large downfield shift suggests that the enzyme phosphoryl group is highly strained with an O-P-O bond angle of under 100 degrees.", "contents": "31P NMR of phosphate and phosphonate complexes of metalloalkaline phosphatases. 31P NMR spectra of phosphate and phosphonate complexes of Escherichia coli alkaline phosphatase have been obtained by Fourier transform NMR methods. One equivalent of P1i, bound to Zn(II) alkaline phosphatase, pH 8, gives rise to a single 31P resonance 2 ppm downfield from that for Pi, and assignable to the noncovalent complex, E-P. Inorganic phosphate in excess of 1 eq per enzyme dimer gives rise to a resonance at the position expected for free Pi. At pH 5.1, a second resonance appears 8.5 ppm downfield from that for free Pi, and is assignable to the covalent complex, E-P. The large downfield shift suggests that the enzyme phosphoryl group is highly strained with an O-P-O bond angle of under 100 degrees."}
{"id": "PMID:2607", "title": "Isolation and characterization of indole-3-acetaldehyde reductases from Cucumis sativus.", "content": "In a continuing study of the biosynthetic pathway and regulatory mechanisms governing indole-3-acetic acid (auxin) formation, we report the isolation and initial characterization of three distinct indole-3-acetaldehyde reductases from cucumber seedlings. These enzymes catalyze the reduction of indole-3-acetaldehyde to indole-3-ethanol with the concomitant oxidation of NAD(P)H to NAD(P)+. Two of the reductases are specific for NADPH as second substrate, while the third is specific for NADH. The enzymes show a strong specificity for indoleacetaldehyde, with apparent Km values of 73mum, 130mum, and 400mum being calculated for the two NADPH-specific reductases and the NADH-specific reductase, respectively. Under no conditions of substrate concentration, incubation time, or assay method could the reverse reaction be observed. Chromatography on a calibrated Sephadex gel column led to estimated molecualr weights of 52,000 and 17,000 for the NADPH-specific reductases, while a value of 33,000 was obtained for the NADH-specific reductase. Both NADPH-specific reductases showed a pH optimum of 5.2 with a secondary optimum at 7.0, and both enzymes were activated by increasing ionic strength. The NADH-specific reductase showed a pH optimum of 7.0 with a secondary optimum at 6.1 and was slightly inhibited by increasing ionic strength.", "contents": "Isolation and characterization of indole-3-acetaldehyde reductases from Cucumis sativus. In a continuing study of the biosynthetic pathway and regulatory mechanisms governing indole-3-acetic acid (auxin) formation, we report the isolation and initial characterization of three distinct indole-3-acetaldehyde reductases from cucumber seedlings. These enzymes catalyze the reduction of indole-3-acetaldehyde to indole-3-ethanol with the concomitant oxidation of NAD(P)H to NAD(P)+. Two of the reductases are specific for NADPH as second substrate, while the third is specific for NADH. The enzymes show a strong specificity for indoleacetaldehyde, with apparent Km values of 73mum, 130mum, and 400mum being calculated for the two NADPH-specific reductases and the NADH-specific reductase, respectively. Under no conditions of substrate concentration, incubation time, or assay method could the reverse reaction be observed. Chromatography on a calibrated Sephadex gel column led to estimated molecualr weights of 52,000 and 17,000 for the NADPH-specific reductases, while a value of 33,000 was obtained for the NADH-specific reductase. Both NADPH-specific reductases showed a pH optimum of 5.2 with a secondary optimum at 7.0, and both enzymes were activated by increasing ionic strength. The NADH-specific reductase showed a pH optimum of 7.0 with a secondary optimum at 6.1 and was slightly inhibited by increasing ionic strength."}
{"id": "PMID:2608", "title": "Calcium transport driven by a proton gradient and inverted membrane vesicles of Escherichia coli.", "content": "Calcium transport into inverted vesicles of Escherichia coli was observed to occur without an exogenous energy source when an artificial proton gradient was used. The orientation of the proton gradient was acid inside and alkaline outside. Either phosphate or oxalate was necessary for transport, as was found for respiratory-driven or ATP-driven uptake (Tsuchiya, T., and Rosen, B.P. (1975) J. Biol. Chem. 250, 7687-7692). Phosphate accumulation was found to occur in conjunction with calcium accumulation. Calcium transport driven by an artificial proton gradient was stimulated by dicyclohexylcarbodiimide, an inhibitor of the Mg2+ATPase (EC 3.6.1.3). Valinomycin, which catalyzes electrogenic potassium movement, stimulated calcium accumulation, while nigericin, which catalyzes electroneutral exchange of potassium and protons, inhibited both artificial proton gradient-driven transport and respiratory-driven transport. Other properties of the proton gradient-driven system and the previously reported energy-linked calcium transport system are similar, indicating that calcium is transported by the same carrier whether energy is supplied through an artificial proton gradient or an energized membrane state. These results suggest the existence of a calcium/proton antiport.", "contents": "Calcium transport driven by a proton gradient and inverted membrane vesicles of Escherichia coli. Calcium transport into inverted vesicles of Escherichia coli was observed to occur without an exogenous energy source when an artificial proton gradient was used. The orientation of the proton gradient was acid inside and alkaline outside. Either phosphate or oxalate was necessary for transport, as was found for respiratory-driven or ATP-driven uptake (Tsuchiya, T., and Rosen, B.P. (1975) J. Biol. Chem. 250, 7687-7692). Phosphate accumulation was found to occur in conjunction with calcium accumulation. Calcium transport driven by an artificial proton gradient was stimulated by dicyclohexylcarbodiimide, an inhibitor of the Mg2+ATPase (EC 3.6.1.3). Valinomycin, which catalyzes electrogenic potassium movement, stimulated calcium accumulation, while nigericin, which catalyzes electroneutral exchange of potassium and protons, inhibited both artificial proton gradient-driven transport and respiratory-driven transport. Other properties of the proton gradient-driven system and the previously reported energy-linked calcium transport system are similar, indicating that calcium is transported by the same carrier whether energy is supplied through an artificial proton gradient or an energized membrane state. These results suggest the existence of a calcium/proton antiport."}
{"id": "PMID:2609", "title": "Stoichiometry of H+ ejection during respiration-dependent accumulation of Ca2+ by rat liver mitochondria.", "content": "We have investigated the energy-dependent uptake of Ca2+ by rat liver mitochondria with succinate as respiratory substrate with rotenone added to block NAD-linked electron transport. In the presence of 3-hydroxybutyric or other permeant monocarboxylic acids Ca2+ was taken up to extents approaching those seen in the presence of phosphate. The quantitative relationship between cation and anion uptake was determined from the slope of a plot of 3-hydroxybutyrate uptake against Ca2+ uptake, a method which allowed determination of the stoichiometry without requiring ambiguous corrections for early nonenergized or nonstoichiometric binding events. This procedure showed that 2 molecules of 3-hydroxtbutyrate were accumulated with each Ca2+ ion. Under these conditions close to 2 Ca2+ ions and 4 molecules of 3-hydroxybutyrate were accumulated per pair of electrons per energy-conserving site of the respiratory chain. Since 3-hydroxybutyrate must be protonated to pass the membrane as the undissociated free acid, it is concluded that 4 protons were ejected (and subsequently reabsorbed) per pair of electrons per energy-conserving site, in contrast to the value 2.0 postulated by the chemiosmotic hypothesis.", "contents": "Stoichiometry of H+ ejection during respiration-dependent accumulation of Ca2+ by rat liver mitochondria. We have investigated the energy-dependent uptake of Ca2+ by rat liver mitochondria with succinate as respiratory substrate with rotenone added to block NAD-linked electron transport. In the presence of 3-hydroxybutyric or other permeant monocarboxylic acids Ca2+ was taken up to extents approaching those seen in the presence of phosphate. The quantitative relationship between cation and anion uptake was determined from the slope of a plot of 3-hydroxybutyrate uptake against Ca2+ uptake, a method which allowed determination of the stoichiometry without requiring ambiguous corrections for early nonenergized or nonstoichiometric binding events. This procedure showed that 2 molecules of 3-hydroxtbutyrate were accumulated with each Ca2+ ion. Under these conditions close to 2 Ca2+ ions and 4 molecules of 3-hydroxybutyrate were accumulated per pair of electrons per energy-conserving site of the respiratory chain. Since 3-hydroxybutyrate must be protonated to pass the membrane as the undissociated free acid, it is concluded that 4 protons were ejected (and subsequently reabsorbed) per pair of electrons per energy-conserving site, in contrast to the value 2.0 postulated by the chemiosmotic hypothesis."}
{"id": "PMID:2610", "title": "Identification of albumin as the serum factor essential for the growth of activated human lymphocytes.", "content": "Albumin from human, bovine, or rabbit serum supported the growth of concanavalin A-stimulated human thymus-derived lymphocytes equally well. This activity was completely abolished by pepsin digestion. It was shown for bovine serum albumin that the albumin molecule itself, and neither an impurity nor a factor bound to albumin was essential for the growth of lymphocytes. This conclusion was based on observations that the growth-promoting activity could not be removed from albumin, and that the specific activity of albumin remained unaltered after the following procedures: molecular sieving at pH 7.5 at pH 3.0, and in 8 M urea at pH 6.6; ion exchange chromatography at pH 4.3 and in 8 M urea at pH 7.2; isoelectric focusing; charcoal treatment; acetone precipitation; and reduction with 2-mercaptoethanol in the presence of 8 M urea. Dimeric albumin was found to support growth of lymphocytes as well as monomeric albumin, and mercaptalbumin and non-mercaptalbumin were shown to have equal activity.", "contents": "Identification of albumin as the serum factor essential for the growth of activated human lymphocytes. Albumin from human, bovine, or rabbit serum supported the growth of concanavalin A-stimulated human thymus-derived lymphocytes equally well. This activity was completely abolished by pepsin digestion. It was shown for bovine serum albumin that the albumin molecule itself, and neither an impurity nor a factor bound to albumin was essential for the growth of lymphocytes. This conclusion was based on observations that the growth-promoting activity could not be removed from albumin, and that the specific activity of albumin remained unaltered after the following procedures: molecular sieving at pH 7.5 at pH 3.0, and in 8 M urea at pH 6.6; ion exchange chromatography at pH 4.3 and in 8 M urea at pH 7.2; isoelectric focusing; charcoal treatment; acetone precipitation; and reduction with 2-mercaptoethanol in the presence of 8 M urea. Dimeric albumin was found to support growth of lymphocytes as well as monomeric albumin, and mercaptalbumin and non-mercaptalbumin were shown to have equal activity."}
{"id": "PMID:2611", "title": "The fluorimetric detection of pesticides on aluminium oxide layers.", "content": "Several pesticides have been investigated for their fluorigenic properties on acidic and basic aluminium oxide layers. Fluorescence was obtained in several instances and the relative intensities were observed. Fluorescence spectra were recorded for the best fluorescence obtained before and after heat treatment of the chromatogram. The results are compared with those already reported for silica gel layers.", "contents": "The fluorimetric detection of pesticides on aluminium oxide layers. Several pesticides have been investigated for their fluorigenic properties on acidic and basic aluminium oxide layers. Fluorescence was obtained in several instances and the relative intensities were observed. Fluorescence spectra were recorded for the best fluorescence obtained before and after heat treatment of the chromatogram. The results are compared with those already reported for silica gel layers."}
{"id": "PMID:2612", "title": "Determination of indomethacin in serum and urine by electron-capture gas-liquid chromatography.", "content": "A specific and sensitive method for the quantitative determination of indomethacin in serum and urine is described. The drug is extracted at pH 5.0 with 1,2-dichloroethane and a portion of the organic extract is concentrated and made to react with diazoethane in diethyl ether. The ethyl ester derivative is analyzed by electron-capture gas-liquid chromatography, quantitation being achieved by comparison of peak areas for samples and standards, which are prepared in serum or urine and treated in the same manner as the samples. The limit of sensitivity is 50 ng/ml and the relative standard derivation for repeat determinations on the same sample is about 3%.", "contents": "Determination of indomethacin in serum and urine by electron-capture gas-liquid chromatography. A specific and sensitive method for the quantitative determination of indomethacin in serum and urine is described. The drug is extracted at pH 5.0 with 1,2-dichloroethane and a portion of the organic extract is concentrated and made to react with diazoethane in diethyl ether. The ethyl ester derivative is analyzed by electron-capture gas-liquid chromatography, quantitation being achieved by comparison of peak areas for samples and standards, which are prepared in serum or urine and treated in the same manner as the samples. The limit of sensitivity is 50 ng/ml and the relative standard derivation for repeat determinations on the same sample is about 3%."}
{"id": "PMID:2614", "title": "Separation of some typical Krebs cycle acids by high-speed isotachophoresis.", "content": "In order to perform a required separation, an experimental procedure for the selection of suitable operating conditions is suggested and discussed. It is based on measurements of the dependences of the relative effective mobilities of the components under investigation on the pH of the leading electrolyte. The procedure was applied to a set of typical Krebs cycle acids and the values of the relative effective mobilities measured are given in tables and graphs. A pH of 3.8 was selected as the most suitable. At this value, the acids investigated were successfully separated in less than 4 min using 0.011 M hydrochloric acid + beta-alanine as the leading electrolyte.", "contents": "Separation of some typical Krebs cycle acids by high-speed isotachophoresis. In order to perform a required separation, an experimental procedure for the selection of suitable operating conditions is suggested and discussed. It is based on measurements of the dependences of the relative effective mobilities of the components under investigation on the pH of the leading electrolyte. The procedure was applied to a set of typical Krebs cycle acids and the values of the relative effective mobilities measured are given in tables and graphs. A pH of 3.8 was selected as the most suitable. At this value, the acids investigated were successfully separated in less than 4 min using 0.011 M hydrochloric acid + beta-alanine as the leading electrolyte."}
{"id": "PMID:2615", "title": "Rapid gas chromatographic determination of underivatized theophylline in whole blood.", "content": "A rapid gas chromatographic method for the determination of underivatized theophylline in whole blood is described. Theophylline is extracted from acidified blood and chromatographed directly using cyheptamide as an internal standard. Concentrations of the drug down to 2 mug/ml in blood could be determined with recoveries ranging from 90 to 110%.", "contents": "Rapid gas chromatographic determination of underivatized theophylline in whole blood. A rapid gas chromatographic method for the determination of underivatized theophylline in whole blood is described. Theophylline is extracted from acidified blood and chromatographed directly using cyheptamide as an internal standard. Concentrations of the drug down to 2 mug/ml in blood could be determined with recoveries ranging from 90 to 110%."}
{"id": "PMID:2616", "title": "Plasma androgen responce to hCG stimulation in prepubertal boys with hypospadias and cryptorchidism.", "content": "Serum levels of testosterone, androstenedione and dehydroepiandrosterone were measured before and after 5 days of treatment with hCG (2000 IU/d) in 36 prepubertal boys with cryptorchidism and 11 with hypospadias in order to determine whether a defect in androgen synthesis could be a common cause for these disorders. Baseline and stimulated levels of testosterone, androstenedione and dehydroepiandrosterone were similar in patients with unilateral cryptorchidism, monorchism and hypospadias; baseline and stimulated levels of testosterone were lower in boys with bilateral cryptorchidism. Testosterone levels did not correlate with either the anatomical location of the testis in patients with unilateral cryptorchidism or with the site of the urethra in boys with hypospadias. Seven of 36 patients with cryptorchidism had a positive family history of a similar disorder; testosterone levels were similar in patients with and without a family history. It is concluded: 1) in all patients studied, the gonadotropin dependent phase of testosterone production is present; 2) hCG stimulation cannot detect unilateral Leydig cell dysfunction; and 3) in familial cases of cryptorchidism, some factor other than an abnormality in androgen synthesis may be responsible for the hereditary tendency.", "contents": "Plasma androgen responce to hCG stimulation in prepubertal boys with hypospadias and cryptorchidism. Serum levels of testosterone, androstenedione and dehydroepiandrosterone were measured before and after 5 days of treatment with hCG (2000 IU/d) in 36 prepubertal boys with cryptorchidism and 11 with hypospadias in order to determine whether a defect in androgen synthesis could be a common cause for these disorders. Baseline and stimulated levels of testosterone, androstenedione and dehydroepiandrosterone were similar in patients with unilateral cryptorchidism, monorchism and hypospadias; baseline and stimulated levels of testosterone were lower in boys with bilateral cryptorchidism. Testosterone levels did not correlate with either the anatomical location of the testis in patients with unilateral cryptorchidism or with the site of the urethra in boys with hypospadias. Seven of 36 patients with cryptorchidism had a positive family history of a similar disorder; testosterone levels were similar in patients with and without a family history. It is concluded: 1) in all patients studied, the gonadotropin dependent phase of testosterone production is present; 2) hCG stimulation cannot detect unilateral Leydig cell dysfunction; and 3) in familial cases of cryptorchidism, some factor other than an abnormality in androgen synthesis may be responsible for the hereditary tendency."}
{"id": "PMID:2617", "title": "A rabbit reticulocyte model for the role of hemin-controlled repressor in hypochromic anemias.", "content": "Hemin allows maximal protein synthesis in intact rabbit reticulocytes and their cell-free lysate preparations by retarding the formation of a translational repressor (HCR) found in the postribosomal supernate. In order to evaluate the role of HCR in the pathogenesis of hypochromic anemias, HCR was isolated and partially purified from intact rabbit reticulocytes incubated in vitro with either 0.1 mM alpha,alpha-dipyridyl (an iron-chelating agent) or 0.1 M ethanol. Both of these agents inhibit reticulocyte protein synthesis. Hemin (50 muM) protects against the inhibition by both agents. A ferrous iron-transferrin mixture, however, protects only against alpha,alpha-dipyridyl. Both alpha,alpha-dipyridyl and ethanol inhibit heme synthesis before the time that protein synthesis is affected, while neither lowers either ATP or GSH levels. These results indicate that while both agents inhibit heme synthesis, alpha,alpha-dipyridyl does so by inducing iron deficiency while ethanol works at a non-iron-requiring step. When HCR was isolated from intact cells and assayed in the reticulocyte cell-free systems, plus and minus hemin, premature appearance of HCR was found in cells incubated in vitro with alpha,alpha-dipyridyl or ethanol. When hemin was present in the intact cell incubation, the appearance of HCR was retarded. The HCR from alpha,alpha-dipyridyl ethanol-treated cells was partially purified and eluted at the same location on a Sephadex G-200 column (molecular weight approximately 3 x 10(5)) as that from postribosomal supernates incubated minus hemin. In addition rabbits with phenylhydrazine-induced hemolytic anemia were given intravenous ethanol in vivo at a dose of 0.4 ml/kg. This concentration of alcohol resulted in an inhibition of the rate of heme synthesis and protein synthesis as well as an acceleration of HCR formation in reticulocytes. The HCR from these in vivo treated rabbits was isolated, partially purified, and assayed in an identical fashion as the in vitro experiments. These in vivo experiments further support the physiological and pathophysiological role of HCR in reticulocytes. On the basis of these results a model for a role of HCR in some of the hypochromic anemias is proposed. In iron deficiency or chronic disease (where iron is not available to the erythroblast for heme synthesis) HCR appears prematurely and inhibits protein synthesis. When heme synthesis is inhibited by ethanol but there is sufficient intracellular iron, HCR appears prematurely and inhibits protein synthesis, iron accumulates in the erythroblast, and the end result is sideroblastic anemia.", "contents": "A rabbit reticulocyte model for the role of hemin-controlled repressor in hypochromic anemias. Hemin allows maximal protein synthesis in intact rabbit reticulocytes and their cell-free lysate preparations by retarding the formation of a translational repressor (HCR) found in the postribosomal supernate. In order to evaluate the role of HCR in the pathogenesis of hypochromic anemias, HCR was isolated and partially purified from intact rabbit reticulocytes incubated in vitro with either 0.1 mM alpha,alpha-dipyridyl (an iron-chelating agent) or 0.1 M ethanol. Both of these agents inhibit reticulocyte protein synthesis. Hemin (50 muM) protects against the inhibition by both agents. A ferrous iron-transferrin mixture, however, protects only against alpha,alpha-dipyridyl. Both alpha,alpha-dipyridyl and ethanol inhibit heme synthesis before the time that protein synthesis is affected, while neither lowers either ATP or GSH levels. These results indicate that while both agents inhibit heme synthesis, alpha,alpha-dipyridyl does so by inducing iron deficiency while ethanol works at a non-iron-requiring step. When HCR was isolated from intact cells and assayed in the reticulocyte cell-free systems, plus and minus hemin, premature appearance of HCR was found in cells incubated in vitro with alpha,alpha-dipyridyl or ethanol. When hemin was present in the intact cell incubation, the appearance of HCR was retarded. The HCR from alpha,alpha-dipyridyl ethanol-treated cells was partially purified and eluted at the same location on a Sephadex G-200 column (molecular weight approximately 3 x 10(5)) as that from postribosomal supernates incubated minus hemin. In addition rabbits with phenylhydrazine-induced hemolytic anemia were given intravenous ethanol in vivo at a dose of 0.4 ml/kg. This concentration of alcohol resulted in an inhibition of the rate of heme synthesis and protein synthesis as well as an acceleration of HCR formation in reticulocytes. The HCR from these in vivo treated rabbits was isolated, partially purified, and assayed in an identical fashion as the in vitro experiments. These in vivo experiments further support the physiological and pathophysiological role of HCR in reticulocytes. On the basis of these results a model for a role of HCR in some of the hypochromic anemias is proposed. In iron deficiency or chronic disease (where iron is not available to the erythroblast for heme synthesis) HCR appears prematurely and inhibits protein synthesis. When heme synthesis is inhibited by ethanol but there is sufficient intracellular iron, HCR appears prematurely and inhibits protein synthesis, iron accumulates in the erythroblast, and the end result is sideroblastic anemia."}
{"id": "PMID:2618", "title": "Arylsulfatase B of human lung. Isolation, characterization, and interaction with slow-reacting substance of anaphylaxis.", "content": "Arylsulfatase B was separated from arylsulfatase A in extracts of human lung tissue by anion exchange chromatography and further purified by gel filtration and cation exchange chromatography. Arylsulfatase B of human lung was similar to that enzyme in other tissues and species, exhibiting an apparent mol wt of approximately 60,000, a pH optimum for cleavage of 4-nitrocatechol sulfate (pNCS) of 5.5-6.0, and a sensitivity to inhibition by phosphate ions and especially pyrophosphate in the presence of NaCl. Human lung arylsulfatase B inactivated slow-reacting substance of anaphylaxix (SRS-A) in a linear time-dependent reaction in which the rate was determined by the enzyme-to-substrate ratio. Cleavage of pNCS by human lung arylsulfatase B was competitively suppressed by SRS-A. The finding that human lung tissue contains predominately arylsulfatase B discloses a potential regulatory mechanism for inactivation of SRS-A at or near the site of its generation.", "contents": "Arylsulfatase B of human lung. Isolation, characterization, and interaction with slow-reacting substance of anaphylaxis. Arylsulfatase B was separated from arylsulfatase A in extracts of human lung tissue by anion exchange chromatography and further purified by gel filtration and cation exchange chromatography. Arylsulfatase B of human lung was similar to that enzyme in other tissues and species, exhibiting an apparent mol wt of approximately 60,000, a pH optimum for cleavage of 4-nitrocatechol sulfate (pNCS) of 5.5-6.0, and a sensitivity to inhibition by phosphate ions and especially pyrophosphate in the presence of NaCl. Human lung arylsulfatase B inactivated slow-reacting substance of anaphylaxix (SRS-A) in a linear time-dependent reaction in which the rate was determined by the enzyme-to-substrate ratio. Cleavage of pNCS by human lung arylsulfatase B was competitively suppressed by SRS-A. The finding that human lung tissue contains predominately arylsulfatase B discloses a potential regulatory mechanism for inactivation of SRS-A at or near the site of its generation."}
{"id": "PMID:2619", "title": "Credibility ratings for desensitization and pseudotherapy among moderately and mildly snake-avoidant college students.", "content": "Twenty moderately avoidant and 20 mildly avoidant Ss were chosen as though they were to participate in a snake-avoidance desensitization experiment. After relaxation training, Ss listened to a taped excerpt of either desensitization or pseudotherapy and responded to a 5-item questionnaire that assessed the credibility of the treatment. Mildly avoidant Ss rated desensitization as more credible than pseudotherapy. The implication of this finding is that a great many experimental studies of systematic desensitization have failed to control satisfactorily for the operation of expectancy effects and nonspecific forms of behavioral influence.", "contents": "Credibility ratings for desensitization and pseudotherapy among moderately and mildly snake-avoidant college students. Twenty moderately avoidant and 20 mildly avoidant Ss were chosen as though they were to participate in a snake-avoidance desensitization experiment. After relaxation training, Ss listened to a taped excerpt of either desensitization or pseudotherapy and responded to a 5-item questionnaire that assessed the credibility of the treatment. Mildly avoidant Ss rated desensitization as more credible than pseudotherapy. The implication of this finding is that a great many experimental studies of systematic desensitization have failed to control satisfactorily for the operation of expectancy effects and nonspecific forms of behavioral influence."}
{"id": "PMID:2620", "title": "A comparison of female and male neurotic depressives.", "content": "Female and male neurotic depressives in an outpatient psychiatric clinic were compared on measures of subjective distress, interpersonal concerns, and types of treatment given. There were essentially no differences between the two groups on the patient self-report measures. However, female patients were found to have significantly more therapy sessions that the male neurotic depressives. Also, the female patients were more likely than the male patients to receive psychotropic medication, especially the more potent antidepressant variety.", "contents": "A comparison of female and male neurotic depressives. Female and male neurotic depressives in an outpatient psychiatric clinic were compared on measures of subjective distress, interpersonal concerns, and types of treatment given. There were essentially no differences between the two groups on the patient self-report measures. However, female patients were found to have significantly more therapy sessions that the male neurotic depressives. Also, the female patients were more likely than the male patients to receive psychotropic medication, especially the more potent antidepressant variety."}
{"id": "PMID:2621", "title": "Counter-current immunoelectrophoresis for the diagnosis of pneumococcal chest infection.", "content": "Counter-current immunoelectrohporesis is a rapid sensitive method for detecting pneumococcal capsular antigens in sputum. A result can be obtained within 45 minutes. The optimum conditions for performing the test are given. Counter-current immunoelectrophoresis works with all the 33 pneumococcal antigens tested except type 14. Better precipitin lines are obtained when the gel-support is acid (pH 6-6) than when it is alkaline (pH 8-6). Omniserum is as effective as group-specific sera for the identification of pneumococcal capsular antigens. The findings suggest that pneumococcal infection was present in 44% of 300 unselected suspected chest infections. Culture for pneumococci was positive in only 15% of these cases. The clinical importance of these findings is still being studied but our experience has shown that patients with chest infections should have effective antipneumococcal antibiotics as part of their regimen and that the laboratory diagnosis may be made quickly and accurately by counter-current immunoelectrophoresis.", "contents": "Counter-current immunoelectrophoresis for the diagnosis of pneumococcal chest infection. Counter-current immunoelectrohporesis is a rapid sensitive method for detecting pneumococcal capsular antigens in sputum. A result can be obtained within 45 minutes. The optimum conditions for performing the test are given. Counter-current immunoelectrophoresis works with all the 33 pneumococcal antigens tested except type 14. Better precipitin lines are obtained when the gel-support is acid (pH 6-6) than when it is alkaline (pH 8-6). Omniserum is as effective as group-specific sera for the identification of pneumococcal capsular antigens. The findings suggest that pneumococcal infection was present in 44% of 300 unselected suspected chest infections. Culture for pneumococci was positive in only 15% of these cases. The clinical importance of these findings is still being studied but our experience has shown that patients with chest infections should have effective antipneumococcal antibiotics as part of their regimen and that the laboratory diagnosis may be made quickly and accurately by counter-current immunoelectrophoresis."}
{"id": "PMID:2622", "title": "Use of anaerobic culture for the improved isolation of Streptococcus pneumoniae.", "content": "The following report compares the results of aerobic and anaerobic cultivation for the primary isolation of Streptococcus pneumoniae (the pneumococcus) from the respiratory tract of children. Of 414 specimens of respiratory tract secretions cultured, 65 (15-7%) yielded pneumococci; 31 (47-7%) grew both aerobically and anaerobically, but 34 (52-3%) strains were isolated only from the anaerobic culture. Pneumococci cultured anaerobically with added carbon dioxide characteristically produce large mucoid colonies which are more easily distinguished than the 'normal' colonies commonly seen in the mixed flora isolated from respiratory sites. This advantage justifies the inclusion of anaerobic culture when attempting to isolate Str. pneumoniae from clinical material.", "contents": "Use of anaerobic culture for the improved isolation of Streptococcus pneumoniae. The following report compares the results of aerobic and anaerobic cultivation for the primary isolation of Streptococcus pneumoniae (the pneumococcus) from the respiratory tract of children. Of 414 specimens of respiratory tract secretions cultured, 65 (15-7%) yielded pneumococci; 31 (47-7%) grew both aerobically and anaerobically, but 34 (52-3%) strains were isolated only from the anaerobic culture. Pneumococci cultured anaerobically with added carbon dioxide characteristically produce large mucoid colonies which are more easily distinguished than the 'normal' colonies commonly seen in the mixed flora isolated from respiratory sites. This advantage justifies the inclusion of anaerobic culture when attempting to isolate Str. pneumoniae from clinical material."}
{"id": "PMID:2623", "title": "Factors affecting the assay of gentamicin by the plate diffusion method.", "content": "Standard curves were prepared by plotting log gentamicin concentration against zone diameter using a conventional plate diffusion method. Results were obtained at varying concentrations of sodium chloride and at different pHs. Under optimum conditions the range in zone diameters was markedly increased, thus considerably improving the potential accuracy of the plate assay method.", "contents": "Factors affecting the assay of gentamicin by the plate diffusion method. Standard curves were prepared by plotting log gentamicin concentration against zone diameter using a conventional plate diffusion method. Results were obtained at varying concentrations of sodium chloride and at different pHs. Under optimum conditions the range in zone diameters was markedly increased, thus considerably improving the potential accuracy of the plate assay method."}
{"id": "PMID:2624", "title": "An optimized semi-automatic rate method for serum glutathione reductase activity and its application to patients with malignant disease.", "content": "An improved and optimized method for serum glutathione reductase is described. The reference range for normal subjects is 47-79 IU/1. The method is more sensitive than conventional enzyme tests in the detection of malignant disease. It was not raised more frequently in patients with clinical evidence of metastases than in those clinically free of such metastases, and it did not seem to correlate with prognosis among those patients who failed to survive six months from the time the analysis was first conducted.", "contents": "An optimized semi-automatic rate method for serum glutathione reductase activity and its application to patients with malignant disease. An improved and optimized method for serum glutathione reductase is described. The reference range for normal subjects is 47-79 IU/1. The method is more sensitive than conventional enzyme tests in the detection of malignant disease. It was not raised more frequently in patients with clinical evidence of metastases than in those clinically free of such metastases, and it did not seem to correlate with prognosis among those patients who failed to survive six months from the time the analysis was first conducted."}
{"id": "PMID:2626", "title": "Chemical modulation of agonistic display in Betta splendens.", "content": "Mirror-induced aggressive display of male Siamese fighting fish was reduced by water-borne traces of (a) a pair of male combatants, (b) a nondisplaying fish of either sex, and (c) bits of torn cadual fin. These findings may indicate a mechanism whereby males tolerate the presence of conspecifics to permit nonagressive social interactions.", "contents": "Chemical modulation of agonistic display in Betta splendens. Mirror-induced aggressive display of male Siamese fighting fish was reduced by water-borne traces of (a) a pair of male combatants, (b) a nondisplaying fish of either sex, and (c) bits of torn cadual fin. These findings may indicate a mechanism whereby males tolerate the presence of conspecifics to permit nonagressive social interactions."}
{"id": "PMID:2628", "title": "Qualitative and quantitative changes in carbohydrates during the manufacture of yogurt.", "content": "The average lactose content of yogurt mix was 8.50% and decreased during fermentation to 5.75%. The initial galactose content of the mix was a trace but increased to 1.20% during fermentation. Glucose content remained a trace throughout fermentation. Several brands of commercial yogurt were purchased from local supermarkets and analyzed for carbohydrate content. Lactose ranged from 3.31 to 4.74%, galactose varied from 1.48 to 2.50%, and glucose was only a trace in all samples. Several samples of buttermilk also exhibited the near absence of glucose.", "contents": "Qualitative and quantitative changes in carbohydrates during the manufacture of yogurt. The average lactose content of yogurt mix was 8.50% and decreased during fermentation to 5.75%. The initial galactose content of the mix was a trace but increased to 1.20% during fermentation. Glucose content remained a trace throughout fermentation. Several brands of commercial yogurt were purchased from local supermarkets and analyzed for carbohydrate content. Lactose ranged from 3.31 to 4.74%, galactose varied from 1.48 to 2.50%, and glucose was only a trace in all samples. Several samples of buttermilk also exhibited the near absence of glucose."}
{"id": "PMID:2627", "title": "Effects of adrenalectomy and glucocorticoid therapy on enzyme activities in mammary and adipose tissues from lactating rats.", "content": "Several mammary and adipose enzymes were measured in normal, adrenal-ectomized, adrenalectomized cortisol-treated, and intake-restricted lactating rats. Acetyl-CoA carboxylase, lipoprotein lipase, and triglyceride synthetase complex activities in mammary tissue were unchanged by intake restriction, decreased by adrenalectomy, and increased by glucocorticoid-replacement therapy. Malic dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and lipoprotein lipase activities in adipose were unchanged after adrenalectomy.", "contents": "Effects of adrenalectomy and glucocorticoid therapy on enzyme activities in mammary and adipose tissues from lactating rats. Several mammary and adipose enzymes were measured in normal, adrenal-ectomized, adrenalectomized cortisol-treated, and intake-restricted lactating rats. Acetyl-CoA carboxylase, lipoprotein lipase, and triglyceride synthetase complex activities in mammary tissue were unchanged by intake restriction, decreased by adrenalectomy, and increased by glucocorticoid-replacement therapy. Malic dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and lipoprotein lipase activities in adipose were unchanged after adrenalectomy."}
{"id": "PMID:2629", "title": "B-complex vitamins in cultured and acidified yogurt.", "content": "Studies were to determine the effect of various factors upon B-vitamin content of cultured yogurt and to compare the B-vitamin contents of cultured and direct acidified yogurt. Incubation of yogurt culture at 42 C for 3 h yielded maximum vitamin synthesis concurrent with optimal flavor and texture qualities. A method was standardized for the manufacture of direct acidified yogurt involving the use of Stabilac acidulant and nonfat dry milk, Carboxymethyl cellulose, gelatin, and Starite. Acidified yogurt showed a slightly higher content of certain B-vitamins than the cultured yogurt due to the contribution made by various food additives. Both cultured and acidified yogurt showed good keeping quality and freedom from microbial contaminants during storage at 5 C for 16 days. However, folic acid and vitamin B12 contents decreased 29 and 60% in cultured yogurt and 48 and 54% in acidified yogurt.", "contents": "B-complex vitamins in cultured and acidified yogurt. Studies were to determine the effect of various factors upon B-vitamin content of cultured yogurt and to compare the B-vitamin contents of cultured and direct acidified yogurt. Incubation of yogurt culture at 42 C for 3 h yielded maximum vitamin synthesis concurrent with optimal flavor and texture qualities. A method was standardized for the manufacture of direct acidified yogurt involving the use of Stabilac acidulant and nonfat dry milk, Carboxymethyl cellulose, gelatin, and Starite. Acidified yogurt showed a slightly higher content of certain B-vitamins than the cultured yogurt due to the contribution made by various food additives. Both cultured and acidified yogurt showed good keeping quality and freedom from microbial contaminants during storage at 5 C for 16 days. However, folic acid and vitamin B12 contents decreased 29 and 60% in cultured yogurt and 48 and 54% in acidified yogurt."}
{"id": "PMID:2630", "title": "Microorganisms and characteristics of laban.", "content": "Laban had a titratable acidity of about 1.0%, a pH of 4.25, an ethanol content of 1.25%, and contained 4.2 mug acetaldehyde and 34 mug acetoin/ml. There was no diacetyl. Five microorganisms, classified as Streptococcus thermophilus, Lactobacillus acidophilus, Leuconostoc lactis, Kluyveromyces fragilis, and Saccharomyces cerevisiae, were responsible for the fermentation. Streptococcus thermophilus and L. acidophilus were responsible for acid production with S. thermophilus producing acid more rapidly. Most of the acetaldehyde was produced by K. fragilis, little ethanol was found in absence of S. cerevisiae, and the acetoin was producted by S. thermophilus.", "contents": "Microorganisms and characteristics of laban. Laban had a titratable acidity of about 1.0%, a pH of 4.25, an ethanol content of 1.25%, and contained 4.2 mug acetaldehyde and 34 mug acetoin/ml. There was no diacetyl. Five microorganisms, classified as Streptococcus thermophilus, Lactobacillus acidophilus, Leuconostoc lactis, Kluyveromyces fragilis, and Saccharomyces cerevisiae, were responsible for the fermentation. Streptococcus thermophilus and L. acidophilus were responsible for acid production with S. thermophilus producing acid more rapidly. Most of the acetaldehyde was produced by K. fragilis, little ethanol was found in absence of S. cerevisiae, and the acetoin was producted by S. thermophilus."}
{"id": "PMID:2631", "title": "A mechanism for tobacco smoke-induced allergy.", "content": "Normal CFW mice, when exposed to tobacco smoke, showed a significantly increased susceptibility to the lethal effects of histamine. The LD50 for mice subjected to smoke was 45 mg/kg of histamine, whereas in normal CFW mice the LD50 was 1,100 mg/kg. The histamine susceptibility of smoked mice was markedly diminished by injecting the animals with isoproterenol. Normal CFW mice, as well as sham control mice, exhibited an epinephrine-induced hyperglycemia, whereas the blood glucose values for smoked mice given epinephrine were essentially the same as those for sham mice given only saline. This observation indicates that tobacco smoke may contain a component which causes an autonomic imbalance, hence rendering the mice more susceptible to histamine. This tobacco smoke-induced allergy is probably related to a blockade of adrenergic receptors and not to an immunologic phenomenon.", "contents": "A mechanism for tobacco smoke-induced allergy. Normal CFW mice, when exposed to tobacco smoke, showed a significantly increased susceptibility to the lethal effects of histamine. The LD50 for mice subjected to smoke was 45 mg/kg of histamine, whereas in normal CFW mice the LD50 was 1,100 mg/kg. The histamine susceptibility of smoked mice was markedly diminished by injecting the animals with isoproterenol. Normal CFW mice, as well as sham control mice, exhibited an epinephrine-induced hyperglycemia, whereas the blood glucose values for smoked mice given epinephrine were essentially the same as those for sham mice given only saline. This observation indicates that tobacco smoke may contain a component which causes an autonomic imbalance, hence rendering the mice more susceptible to histamine. This tobacco smoke-induced allergy is probably related to a blockade of adrenergic receptors and not to an immunologic phenomenon."}
{"id": "PMID:2633", "title": "Regulation of the antibody response to type III pneumococcal polysaccharide. V. Ontogeny of factors influencing the magnitude of the plaque-forming cell response.", "content": "Mice of different ages were evaluated with respect to their ability to give a plaque-forming cell (PFC) response to Type III pneumococcal polysaccharide (SSSIII), as well as the degree of amplifier and suppressor thymus-derived(T) cell activity present. Although the magnitude of the PFC response to an optimally immunogenic dose of SSS-III for 2-and 3-week old mice was only 7% and 14%, respectively, of that produced by adult (8-week old) mice, values comparable to those of adult animals were attained by 4 weeks of age; no significant changes in the ability to respond to SSS-III occurred thereafter. Amplifier T cell activity, which was minimal at 2 to 4 weeks of age, matured slowly and did not reach a maximum until 8 to 10 weeks of age. By contrast, suppressor T cell activity appeared to be fully developed at least as early as 2 weeks of age; here, the inhibitory effects produced could by abrogated by depletion of T cells, indicating that the unresponsiveneness induced by such cells does not result in the depletion ot irreversible inactivation of B cells capable of responding to SSS-III. These findings suggest that the inhibitory effects of suppressor T cells are predominant in young mice and that such cells may play an important role in determining the ease with which unresponsiveness is induced in neonates, and in the prevention of autoimmune disease. Also, studies conducted with adult-thymectomized mice showed that both amplifier and suppressor T cells, once seeded to the periphery, are stable and do not depend upon the presence of intact thymus for the expression or renewal of their activity.", "contents": "Regulation of the antibody response to type III pneumococcal polysaccharide. V. Ontogeny of factors influencing the magnitude of the plaque-forming cell response. Mice of different ages were evaluated with respect to their ability to give a plaque-forming cell (PFC) response to Type III pneumococcal polysaccharide (SSSIII), as well as the degree of amplifier and suppressor thymus-derived(T) cell activity present. Although the magnitude of the PFC response to an optimally immunogenic dose of SSS-III for 2-and 3-week old mice was only 7% and 14%, respectively, of that produced by adult (8-week old) mice, values comparable to those of adult animals were attained by 4 weeks of age; no significant changes in the ability to respond to SSS-III occurred thereafter. Amplifier T cell activity, which was minimal at 2 to 4 weeks of age, matured slowly and did not reach a maximum until 8 to 10 weeks of age. By contrast, suppressor T cell activity appeared to be fully developed at least as early as 2 weeks of age; here, the inhibitory effects produced could by abrogated by depletion of T cells, indicating that the unresponsiveneness induced by such cells does not result in the depletion ot irreversible inactivation of B cells capable of responding to SSS-III. These findings suggest that the inhibitory effects of suppressor T cells are predominant in young mice and that such cells may play an important role in determining the ease with which unresponsiveness is induced in neonates, and in the prevention of autoimmune disease. Also, studies conducted with adult-thymectomized mice showed that both amplifier and suppressor T cells, once seeded to the periphery, are stable and do not depend upon the presence of intact thymus for the expression or renewal of their activity."}
{"id": "PMID:2634", "title": "The role of the capsular polysaccharide in the activation of the alternative pathway by the pneumococcus.", "content": "Previous studies have shown that when pneumococci are incubated in normal, nonimmune serum, they activate the alternative pathway and opsonically active C3b is fixed to the surface of the organism. Other studies have demonstrated that C3-dependent opsonization via the alternative pathway plays a significant role in the nonimmune host's defense against the pneumococcus. The present studies concern the role of the capsular polysaccharide in initiating the activation of the alternative pathway by the pneumococcus. Some pneumococcal capsular polysaccharide types, but not all, are able to activate the alternative pathway. Soluble purified capsular polysaccharide types 1, 4 and 25 activate the alternative pathway, whereas types 2, 3, 14, and 19 do not. Since the capsular polysaccharides exist in their native form attached to the pneumococcal surface, selected capsular polysaccharides were also tested for their ability to activate the alternative pathway when attached to a particulate carrier, sheep erythrocytes. Capsular polysaccharide types 2 and 3 failed to activate the alternative pathway when attached to sheep erythrocytes, paralleling the results obtained when these capsular polysaccharides were in solution. In contrast, the type 25 capsular polysaccharide not only activated the alternative pathway when attached to sheep erythrocytes, as it had when in solution, but it also initiated alternative pathway-mediated lysis of the erythrocytes. The capsular polysaccharide is not required for the activation of the alternative pathway by the pneumococcus. Although all types of encapsulated pneumococci are able to activate the alternative pathway, not all the purified capsular polysaccharide types are able to do so. In addition, a nonencapsulated pneumococcus, derived originally from a type 2 organism, activates the alternative pathway as well as a fully encapsulated type 2 pneumococcus.", "contents": "The role of the capsular polysaccharide in the activation of the alternative pathway by the pneumococcus. Previous studies have shown that when pneumococci are incubated in normal, nonimmune serum, they activate the alternative pathway and opsonically active C3b is fixed to the surface of the organism. Other studies have demonstrated that C3-dependent opsonization via the alternative pathway plays a significant role in the nonimmune host's defense against the pneumococcus. The present studies concern the role of the capsular polysaccharide in initiating the activation of the alternative pathway by the pneumococcus. Some pneumococcal capsular polysaccharide types, but not all, are able to activate the alternative pathway. Soluble purified capsular polysaccharide types 1, 4 and 25 activate the alternative pathway, whereas types 2, 3, 14, and 19 do not. Since the capsular polysaccharides exist in their native form attached to the pneumococcal surface, selected capsular polysaccharides were also tested for their ability to activate the alternative pathway when attached to a particulate carrier, sheep erythrocytes. Capsular polysaccharide types 2 and 3 failed to activate the alternative pathway when attached to sheep erythrocytes, paralleling the results obtained when these capsular polysaccharides were in solution. In contrast, the type 25 capsular polysaccharide not only activated the alternative pathway when attached to sheep erythrocytes, as it had when in solution, but it also initiated alternative pathway-mediated lysis of the erythrocytes. The capsular polysaccharide is not required for the activation of the alternative pathway by the pneumococcus. Although all types of encapsulated pneumococci are able to activate the alternative pathway, not all the purified capsular polysaccharide types are able to do so. In addition, a nonencapsulated pneumococcus, derived originally from a type 2 organism, activates the alternative pathway as well as a fully encapsulated type 2 pneumococcus."}
{"id": "PMID:2635", "title": "The effects of age on the immune response to type III pneumococcal polysaccharide (SIII) and bacterial lipopolysaccharide (LPS) in BALB/c, SJL/J, and C3H mice.", "content": "Type III pneumococcal polysaccharide (SIII) and bacterial lipopolysaccharide (LPS) were used to evaluate B cell and T cell regulatory functions in BALB/c, SJL/J, and C3H mice of various ages. It was found that the BALB/c and C3H mice could mount high level plaque-forming cell (PFC) responses to SIII at various ages through 110 weeks whereas the levels of the SJL/J PFC responses had begun to decline by the age of 42 weeks through the age of 80 weeks. BALB/c mice were also capable of producing strong PFC responses to LPS at various ages through 110 weeks whereas the comparable SJL/J PFC responses to LPS had declined by 80 weeks of age. By using anti-lymphocyte serum (ALS) and low-dose paralysis to SIII, it was shown that suppressor T cell activity was apparently greater in young BALB/c mice than in older BALB/c mice. It was also found that paralysis to SIII in BALB/c mice was easier to achieve at an early age. SJL/J mice were found to have the necessary B cell activity to respond to SIII through 80 weeks of age and the PFC responses could be greatly enhanced by ALS. Implications of the roles of regulatory T cells in aging are discussed.", "contents": "The effects of age on the immune response to type III pneumococcal polysaccharide (SIII) and bacterial lipopolysaccharide (LPS) in BALB/c, SJL/J, and C3H mice. Type III pneumococcal polysaccharide (SIII) and bacterial lipopolysaccharide (LPS) were used to evaluate B cell and T cell regulatory functions in BALB/c, SJL/J, and C3H mice of various ages. It was found that the BALB/c and C3H mice could mount high level plaque-forming cell (PFC) responses to SIII at various ages through 110 weeks whereas the levels of the SJL/J PFC responses had begun to decline by the age of 42 weeks through the age of 80 weeks. BALB/c mice were also capable of producing strong PFC responses to LPS at various ages through 110 weeks whereas the comparable SJL/J PFC responses to LPS had declined by 80 weeks of age. By using anti-lymphocyte serum (ALS) and low-dose paralysis to SIII, it was shown that suppressor T cell activity was apparently greater in young BALB/c mice than in older BALB/c mice. It was also found that paralysis to SIII in BALB/c mice was easier to achieve at an early age. SJL/J mice were found to have the necessary B cell activity to respond to SIII through 80 weeks of age and the PFC responses could be greatly enhanced by ALS. Implications of the roles of regulatory T cells in aging are discussed."}
{"id": "PMID:2636", "title": "Production of IgG antibodies and enhanced response of nude mice to DNP-AE-dextran.", "content": "DNP-AE-dextran, prepared by the binding of DNP-epsilon-aminocaproyl residues to animoethylated dextran (predominantly alpha-1,6-linked), induced a T-independent anti-DNP antibody response in mice. However, certain differences were observed between the response to this antigen in normal andnude mice. Thus, the antibody titers of nu/nu mice from day 10 to 38 after immunization were significantly higher than those of nu/+ controls. Furthermore, DNP-AE-dextran induced a weak secondary response in nu/+ but not in nu/nu mice. For both thymusless and normal mice the production of IgG in addition to IgM antibodies to DNP-AE-dextran could be established. The former included antibodies of the IgG1 subclass which were considered to be particularly thymus dependent (1). The higher response of nu/nu mice was reflected mainly in the increased production of IgG antibodies. Under the influence of a graft-vs-host reaction, a 10-fold increase in antibody titers to DNP-AE-dextran was observed, due entirely to an enhanced IgG response.", "contents": "Production of IgG antibodies and enhanced response of nude mice to DNP-AE-dextran. DNP-AE-dextran, prepared by the binding of DNP-epsilon-aminocaproyl residues to animoethylated dextran (predominantly alpha-1,6-linked), induced a T-independent anti-DNP antibody response in mice. However, certain differences were observed between the response to this antigen in normal andnude mice. Thus, the antibody titers of nu/nu mice from day 10 to 38 after immunization were significantly higher than those of nu/+ controls. Furthermore, DNP-AE-dextran induced a weak secondary response in nu/+ but not in nu/nu mice. For both thymusless and normal mice the production of IgG in addition to IgM antibodies to DNP-AE-dextran could be established. The former included antibodies of the IgG1 subclass which were considered to be particularly thymus dependent (1). The higher response of nu/nu mice was reflected mainly in the increased production of IgG antibodies. Under the influence of a graft-vs-host reaction, a 10-fold increase in antibody titers to DNP-AE-dextran was observed, due entirely to an enhanced IgG response."}
{"id": "PMID:2637", "title": "Lymphoid cell fractionation by aggregated immunoglobulin-agarose columns.", "content": "Fractionation by columns of aggregated rat immunoglobulin (Agg Ig)-agarose was investigated as a method of separating different populations of lymphoid cells. With rat spleen cells, Agg Ig columns retained phagocytes, IgM- and IgG-antibody-forming-cells, cells mediating antibody- or PHA-induced lysis of chicken erythrocytes, and specifically immune splenocytes lytic to chicken erythrocytes without exogenous antibody. Agg Ig columns did not selectively remove 'B lymphocytes' (surface-Ig-bearing lymphocytes with or without EAC' receptors), or T lymphocytes capable of PHA-induced proliferation or graft-versus-host reactivity. With mouse spleen cells, Agg Ig columns retained alloimmune cytotoxic T cells.", "contents": "Lymphoid cell fractionation by aggregated immunoglobulin-agarose columns. Fractionation by columns of aggregated rat immunoglobulin (Agg Ig)-agarose was investigated as a method of separating different populations of lymphoid cells. With rat spleen cells, Agg Ig columns retained phagocytes, IgM- and IgG-antibody-forming-cells, cells mediating antibody- or PHA-induced lysis of chicken erythrocytes, and specifically immune splenocytes lytic to chicken erythrocytes without exogenous antibody. Agg Ig columns did not selectively remove 'B lymphocytes' (surface-Ig-bearing lymphocytes with or without EAC' receptors), or T lymphocytes capable of PHA-induced proliferation or graft-versus-host reactivity. With mouse spleen cells, Agg Ig columns retained alloimmune cytotoxic T cells."}
{"id": "PMID:2640", "title": "Rheological studies of Hb SS blood: influence of hematocrit, hypertonicity, separation of cells, deoxygenation, and mixture with normal cells.", "content": "Studies of the rheological properties of Hb SS blood indicate that the marked increase in viscosity with deoxygenation is primarily due to cell-cell interaction of cells which were not permanently deformed. The permanently deformed cells, the bottom fraction of cells separated by centrifugation, show only a fraction of the increase in viscosity compared to top cells, when each was deoxygenated. Top cells showed a greater degree of morphologic change with deoxygenation compared to bottom cells. The viscosity of deoxygenated Hb SS blood was disproportionately reduced by the addition of compatible deoxygenated Hb AA cells. A mixture of 1/4 Hb AA cells and 3/4 Hb SS cells reduced the viscosity of deoxygenated Hb SS blood 50 per cent. Studies of Hb SS cells in hypertonic media indicate that hypertonicity per se does not cause sickling. Normal and Hb SS erythrocytes both show identical changes in rheological properties when suspended in hypertonic serum. However, changes in oxygen saturation due to a decrease in intracellular pH with certain hypertonic media may lead to sickling when Hb SS blood is at intermediate PO2 levels. The addition of x-ray contrast material to blood results in the changes due to hypertonicity but does not cause sickling of Hb SS cells. The contrast material lowers the pH of the media and raises intracellular pH.", "contents": "Rheological studies of Hb SS blood: influence of hematocrit, hypertonicity, separation of cells, deoxygenation, and mixture with normal cells. Studies of the rheological properties of Hb SS blood indicate that the marked increase in viscosity with deoxygenation is primarily due to cell-cell interaction of cells which were not permanently deformed. The permanently deformed cells, the bottom fraction of cells separated by centrifugation, show only a fraction of the increase in viscosity compared to top cells, when each was deoxygenated. Top cells showed a greater degree of morphologic change with deoxygenation compared to bottom cells. The viscosity of deoxygenated Hb SS blood was disproportionately reduced by the addition of compatible deoxygenated Hb AA cells. A mixture of 1/4 Hb AA cells and 3/4 Hb SS cells reduced the viscosity of deoxygenated Hb SS blood 50 per cent. Studies of Hb SS cells in hypertonic media indicate that hypertonicity per se does not cause sickling. Normal and Hb SS erythrocytes both show identical changes in rheological properties when suspended in hypertonic serum. However, changes in oxygen saturation due to a decrease in intracellular pH with certain hypertonic media may lead to sickling when Hb SS blood is at intermediate PO2 levels. The addition of x-ray contrast material to blood results in the changes due to hypertonicity but does not cause sickling of Hb SS cells. The contrast material lowers the pH of the media and raises intracellular pH."}
{"id": "PMID:2641", "title": "Detection of pneumococcal polysaccharide in the sputum of patients with pneumococcal pneumonia by counterimmunoelectrophoresis.", "content": "Each of 41 patients with bacterial pneumonia was placed into 1 of 4 categories based on the relative clinical certainty of the diagnosis of pneumococcal pneumonia. The frequency of pneumococcal polysaccharide in the sputum by counterimmunoelectrophoresis (CIE) was then noted for each diagnostic category of patients. Detection of pneumococcal polysaccharide in sputum correlated with the diagnostic certainty of pneumococcal pneumonia, while results of culture of sputum were less indicative of pneumococcal infection. Saliva of 83 normal individuals failed to give positive tests for pneumococcal polysaccharide despite the presence of alpha-hemolytic streptococci on culture. Furthermore, the mere presence of pneumococci in cultures did not predict a positive test for polysaccharide by CIE nor did the absence of pneumococci mean that polysaccharide would not be detected. This study suggests that detection of pneumococcal polysaccharide appears more rapid, more sensitive, and more specific than sputum cultures in diagnosing pneumococcal infection of the lung.", "contents": "Detection of pneumococcal polysaccharide in the sputum of patients with pneumococcal pneumonia by counterimmunoelectrophoresis. Each of 41 patients with bacterial pneumonia was placed into 1 of 4 categories based on the relative clinical certainty of the diagnosis of pneumococcal pneumonia. The frequency of pneumococcal polysaccharide in the sputum by counterimmunoelectrophoresis (CIE) was then noted for each diagnostic category of patients. Detection of pneumococcal polysaccharide in sputum correlated with the diagnostic certainty of pneumococcal pneumonia, while results of culture of sputum were less indicative of pneumococcal infection. Saliva of 83 normal individuals failed to give positive tests for pneumococcal polysaccharide despite the presence of alpha-hemolytic streptococci on culture. Furthermore, the mere presence of pneumococci in cultures did not predict a positive test for polysaccharide by CIE nor did the absence of pneumococci mean that polysaccharide would not be detected. This study suggests that detection of pneumococcal polysaccharide appears more rapid, more sensitive, and more specific than sputum cultures in diagnosing pneumococcal infection of the lung."}
{"id": "PMID:2642", "title": "The myofilament lattice: studies on isolated fibers. IV. Lattice equilibria in striated muscle.", "content": "Accounts of similarities between the thick filament lattice of striated muscle and smectic liquid-crystalline structures have focused upon an equilibrium between electrostatic (repulsive) and van der Waal's (attractive) forces. In living, intact muscle the fiber volume constitutes an additional important parameter which influences the amount of interaxial separation between the filaments. This is demonstrable by comparison of the lattice behavior of living fibers with that of fibers from which the sarcolemma has either been removed or made leaky by glycerination. These comparisons were made mainly by low-angle X-ray diffraction under conditions of changes in sarcomere length, ionic strength or osmolarity, and pH. Single fibers with the sarcolemma removed and glycerinated muscle have lattices which behave in accord with equilibrium liquid-crystalline systems in which the thick filament spacing is determined by the balance between electrostatic and van der Waal's forces. Conversely, osmotic and shortening studies demonstrate that the living, intact muscle has a lattice which behaves in accord with the so-called non-equilibrium (volume-constrained) liquid-crystalline condition in which the interaxial separation between the thick filaments is solely due to the amount of volume available as determined by the Donnan steady-state across the sarcolemma.", "contents": "The myofilament lattice: studies on isolated fibers. IV. Lattice equilibria in striated muscle. Accounts of similarities between the thick filament lattice of striated muscle and smectic liquid-crystalline structures have focused upon an equilibrium between electrostatic (repulsive) and van der Waal's (attractive) forces. In living, intact muscle the fiber volume constitutes an additional important parameter which influences the amount of interaxial separation between the filaments. This is demonstrable by comparison of the lattice behavior of living fibers with that of fibers from which the sarcolemma has either been removed or made leaky by glycerination. These comparisons were made mainly by low-angle X-ray diffraction under conditions of changes in sarcomere length, ionic strength or osmolarity, and pH. Single fibers with the sarcolemma removed and glycerinated muscle have lattices which behave in accord with equilibrium liquid-crystalline systems in which the thick filament spacing is determined by the balance between electrostatic and van der Waal's forces. Conversely, osmotic and shortening studies demonstrate that the living, intact muscle has a lattice which behaves in accord with the so-called non-equilibrium (volume-constrained) liquid-crystalline condition in which the interaxial separation between the thick filaments is solely due to the amount of volume available as determined by the Donnan steady-state across the sarcolemma."}
{"id": "PMID:2643", "title": "The identification and subcellular localization of thrombosthenin \"M\", the myosin-like component of pig platelets.", "content": "A protein has been studied which spontaneously precipitates from stored fractions of platelet soluble phase prepared by density gradient centrifugation. It is rich in a Ca2+ ATPase activity which displays an activity/pH profile resembling that of skeletal muscle myosin. Adjustment of freshly prepared soluble phase fractions to 0.6 M with respect to KCl and dilution 1 in 3 results in the precipitations of a protein fraction with essentially the same enzymatic properties as the spontaneously precipitable protein. These two similar proteins represent between 9 and 13% of the soluble phase total protein and each account for almost the whole of divalent cation activated ATPase activity of the soluble phases from which they were derived. The Mg2+ ATPase activity is only about twice purified with respect to the soluble phase enzyme activity, but the Ca2+ ATPase shows a 10-13-fold enrichment. Synthetic actomyosins can be prepared from the two proteins by addition of either platelet or skeletal muscle actin. These show significant increases in Mg2+ ATPase at the most favourable combination ratios. The ratio between the yield of soluble phase protein obtained by dilution precipitation and the lactate dehydrogenase activity of the soluble phase remains constant under a wide range of homogenization and sonication conditions applied to the original whole platelet suspensions. This confirms our earlier view that the soluble phase is a valid intracellular compartment for a considerable proportion of the platelet contractile protein and that in the complex the myosin-like component predominates.", "contents": "The identification and subcellular localization of thrombosthenin \"M\", the myosin-like component of pig platelets. A protein has been studied which spontaneously precipitates from stored fractions of platelet soluble phase prepared by density gradient centrifugation. It is rich in a Ca2+ ATPase activity which displays an activity/pH profile resembling that of skeletal muscle myosin. Adjustment of freshly prepared soluble phase fractions to 0.6 M with respect to KCl and dilution 1 in 3 results in the precipitations of a protein fraction with essentially the same enzymatic properties as the spontaneously precipitable protein. These two similar proteins represent between 9 and 13% of the soluble phase total protein and each account for almost the whole of divalent cation activated ATPase activity of the soluble phases from which they were derived. The Mg2+ ATPase activity is only about twice purified with respect to the soluble phase enzyme activity, but the Ca2+ ATPase shows a 10-13-fold enrichment. Synthetic actomyosins can be prepared from the two proteins by addition of either platelet or skeletal muscle actin. These show significant increases in Mg2+ ATPase at the most favourable combination ratios. The ratio between the yield of soluble phase protein obtained by dilution precipitation and the lactate dehydrogenase activity of the soluble phase remains constant under a wide range of homogenization and sonication conditions applied to the original whole platelet suspensions. This confirms our earlier view that the soluble phase is a valid intracellular compartment for a considerable proportion of the platelet contractile protein and that in the complex the myosin-like component predominates."}
{"id": "PMID:2645", "title": "Control of mouth opening and pharynx protrusion during feeding in the sea anemone Calliactis parasitica.", "content": "1. Activity in all three known conducting systems (the nerve net, SS1, and SS2) may accompany feeding in Calliactis. The most marked response is an increase in pulse frequency in the SS2 (the endodermal slow conducting system) during mouth opening and pharynx protrusion. 2. Electrical stimulation of the SS2 at a frequency of one shock every 5 s elicits mouth opening and pharynx protrusion in the absence of food. 3. A rise in SS2 pulse frequency is also evoked by food extracts, some amino acids, and in particular by the tripeptide reduced glutathione, which produces a response at a concentration of 10(-5) M. 4. Although the SS2 is an endodermal system, the receptors involved in the response to food appear to be ectodermal. 5. The epithelium that lines the pharynx conducts SS1 pulses, but there is some evidence for polarization of conduction.", "contents": "Control of mouth opening and pharynx protrusion during feeding in the sea anemone Calliactis parasitica. 1. Activity in all three known conducting systems (the nerve net, SS1, and SS2) may accompany feeding in Calliactis. The most marked response is an increase in pulse frequency in the SS2 (the endodermal slow conducting system) during mouth opening and pharynx protrusion. 2. Electrical stimulation of the SS2 at a frequency of one shock every 5 s elicits mouth opening and pharynx protrusion in the absence of food. 3. A rise in SS2 pulse frequency is also evoked by food extracts, some amino acids, and in particular by the tripeptide reduced glutathione, which produces a response at a concentration of 10(-5) M. 4. Although the SS2 is an endodermal system, the receptors involved in the response to food appear to be ectodermal. 5. The epithelium that lines the pharynx conducts SS1 pulses, but there is some evidence for polarization of conduction."}
{"id": "PMID:2646", "title": "Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.).", "content": "Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated. For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store. For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field.", "contents": "Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.). Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated. For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store. For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field."}
{"id": "PMID:2647", "title": "Multiple sedimenting species of properdin in human serum and interaction of purified properdin with the third component of complement.", "content": "Normal human serum subjected to sucrose density gradient analysis exhibited multiple sedimenting species of properdin antigen. Properdin antigen distribution was dependent on serum concentration, ionic strength, temperature, and the presence of C3, and was not dependent on the presence of divalent metal cations or blood coagulation. In mixtures of purified components, properdin sedimented heavier in the presence of C3, C3b, or C3c. Addition of factor B to mixtures containing C3 and properdin was without effect. These data provide insights into earlier discrepancies concerning the sedimentation behavior of partially purified properdin, indicate a propensity of some constituents of the alternative pathway to form protein-protein complexes, and suggest caution in interpretation of immunopathological studies in which properdin deposits are found in the presence of C3.", "contents": "Multiple sedimenting species of properdin in human serum and interaction of purified properdin with the third component of complement. Normal human serum subjected to sucrose density gradient analysis exhibited multiple sedimenting species of properdin antigen. Properdin antigen distribution was dependent on serum concentration, ionic strength, temperature, and the presence of C3, and was not dependent on the presence of divalent metal cations or blood coagulation. In mixtures of purified components, properdin sedimented heavier in the presence of C3, C3b, or C3c. Addition of factor B to mixtures containing C3 and properdin was without effect. These data provide insights into earlier discrepancies concerning the sedimentation behavior of partially purified properdin, indicate a propensity of some constituents of the alternative pathway to form protein-protein complexes, and suggest caution in interpretation of immunopathological studies in which properdin deposits are found in the presence of C3."}
{"id": "PMID:2648", "title": "[Cathepsin, phosphoprotein-phosphatase and acid phosphatase in the soluble fraction of the cattle brain cortex: purification and properties (author's transl)].", "content": "Cattle brain cortex was homogenised in 0, 29 mol/1 sucrose and centrifuged at 101 000 X g. The supernatant contains the majority of 3 enzymes participating in protein turnover: cathepsin (EC 3.4.4.23), phosphoprotein phosphatase (EC 3.1.3.16) and acid phosphatase (EC 3.1.3.2). They were separated by chromatography on Sephadex G 200 in neutral buffer. The cathepsin was purified up to 380 fold by gel filtration on Sephadex and column electrophoresis. The pH optimum of cathepsin was 5.7. At 37 degrees C no decrease of activity was measurable during 30 min. The Km was found to be 2.75 mg/ml Casein Hammarsten. The molecular weight by gel filtration and exclusion-gel electrophoresis was about 45 000, corresponding to the cathepsin from human liver (Barrett, A.J. (1970) Biochem. J. 117, 601-607). The sedimentation constant 3.0 S20,W is comparable with the values of proteinase of different origin, and the composition is similar with respect to the high proportion of acidic amino acids. The phosphoprotein phosphatase can be further purified by chromatography on hydroxyapatite and by column electrophoresis. The pH optimum of phosphoprotein phosphatase was about pH 5.5. At 45 degrees C no decrease of activity was measurable during 20 min; the Km was 1.43 mg/ml casein isoelectric. The pH optimum of acid phosphatase was about 5.6. At 54 degrees C NO DECREASE OF ACTIVITY WAs measurable during 30 min; the Km was 2 mumol/1 for Sodium phenolphthalein diphosphate. All three enzymes slowly lost their activity during several weeks at - 4 degrees C, apparently by self digestion in the cold.", "contents": "[Cathepsin, phosphoprotein-phosphatase and acid phosphatase in the soluble fraction of the cattle brain cortex: purification and properties (author's transl)]. Cattle brain cortex was homogenised in 0, 29 mol/1 sucrose and centrifuged at 101 000 X g. The supernatant contains the majority of 3 enzymes participating in protein turnover: cathepsin (EC 3.4.4.23), phosphoprotein phosphatase (EC 3.1.3.16) and acid phosphatase (EC 3.1.3.2). They were separated by chromatography on Sephadex G 200 in neutral buffer. The cathepsin was purified up to 380 fold by gel filtration on Sephadex and column electrophoresis. The pH optimum of cathepsin was 5.7. At 37 degrees C no decrease of activity was measurable during 30 min. The Km was found to be 2.75 mg/ml Casein Hammarsten. The molecular weight by gel filtration and exclusion-gel electrophoresis was about 45 000, corresponding to the cathepsin from human liver (Barrett, A.J. (1970) Biochem. J. 117, 601-607). The sedimentation constant 3.0 S20,W is comparable with the values of proteinase of different origin, and the composition is similar with respect to the high proportion of acidic amino acids. The phosphoprotein phosphatase can be further purified by chromatography on hydroxyapatite and by column electrophoresis. The pH optimum of phosphoprotein phosphatase was about pH 5.5. At 45 degrees C no decrease of activity was measurable during 20 min; the Km was 1.43 mg/ml casein isoelectric. The pH optimum of acid phosphatase was about 5.6. At 54 degrees C NO DECREASE OF ACTIVITY WAs measurable during 30 min; the Km was 2 mumol/1 for Sodium phenolphthalein diphosphate. All three enzymes slowly lost their activity during several weeks at - 4 degrees C, apparently by self digestion in the cold."}
{"id": "PMID:2649", "title": "Polydipsia, hyponatremia, and seizures in psychotic patients.", "content": "Case histories are presented for four psychotic patients who ingested large quantities of water and subsequently developed grand mal seizures and serum sodium levels of less than 121 meq/liter. The physiology of psychogenic polydipsia and related disorders is reviewed. The relation of this disorder to temporal lobe seizures and to the use of phenothiazines is considered.", "contents": "Polydipsia, hyponatremia, and seizures in psychotic patients. Case histories are presented for four psychotic patients who ingested large quantities of water and subsequently developed grand mal seizures and serum sodium levels of less than 121 meq/liter. The physiology of psychogenic polydipsia and related disorders is reviewed. The relation of this disorder to temporal lobe seizures and to the use of phenothiazines is considered."}
{"id": "PMID:2650", "title": "Isolation from bovine brain of a fraction containing capillaries and a fraction containing membrane fragments of the choroid plexus.", "content": "Combined differential and density gradient centrifugation was used for the isolation of a capillary-rich fraction from the cerebral cortex and a brush border containing fraction from the bovine choroid plexus. The activities of gamma-glutamyl transpeptidase and several other marker enzymes were monitored during the fractionation procedure. Electron microscopic examination showed a membrane-rich fraction in the choroid plexus high in the gamma-glutamyl transpeptidase and 5'-nucleotidase activities. From the brain cortex, a capillary-rich fraction was obtained which was high in gamma-glutamyl transpeptidase and alkaline phosphatase activities. A histochemical examination showed gamma-glutamyl transpeptidase activity localized in the capillary walls.", "contents": "Isolation from bovine brain of a fraction containing capillaries and a fraction containing membrane fragments of the choroid plexus. Combined differential and density gradient centrifugation was used for the isolation of a capillary-rich fraction from the cerebral cortex and a brush border containing fraction from the bovine choroid plexus. The activities of gamma-glutamyl transpeptidase and several other marker enzymes were monitored during the fractionation procedure. Electron microscopic examination showed a membrane-rich fraction in the choroid plexus high in the gamma-glutamyl transpeptidase and 5'-nucleotidase activities. From the brain cortex, a capillary-rich fraction was obtained which was high in gamma-glutamyl transpeptidase and alkaline phosphatase activities. A histochemical examination showed gamma-glutamyl transpeptidase activity localized in the capillary walls."}
{"id": "PMID:2651", "title": "Ionic mechanism of 5-hydroxytryptamine induced hyperpolarization and inhibitory junctional potential in body wall muscle cells of Hirudo medicinalis.", "content": "Five-hydroxytryptamine (5-HT) causes a hyperpolarization and increased conductance of the leech body wall muscle cell membrane. If 5-HT is applied in the absence of the Cl minus ion, the response appears as a depolarization, whereas if 5-HT is applied in the absence of the K+ ion, the response is a hyperpolarization. In both cases, the conductance of the muscle cell membrane is increased. Stimulation of the peripheral nerve to the body wall muscle produces a complex junctional potential in muscle cells. Exposing the muscle to d-tubocurarine (d-TC) eliminates the excitatory component (EJP) of the complex potential. The inhibitory potential (IJP) that remains has an equilibrium potential at approximately 65 mV. Furthermore, this IJP appears as a depolarization when the nerve is stimulated in the presence of d-TC and low CL minus, whereas this is not the case if the nerve is stimulated in the presence of d-TC and low K+. The drugs BOL-148 and cyproheptadine block the IJP's in the body wall muscle. These data are interpreted as indicating that 5-HT acts on leech body wall muscle cells by increasing the conductance to the Cl minus ion and that the IJP's caused by nerve stimulation are probably the result of 5-HT release at nerve terminals. As a final point, it has been shown that the inhibition by 5-HT of the spontaneous EJP's that occur on the leech body wall muscle results from an inhibition of central neurons and not from any direct effect on the muscle cell or on peripheral synapses.", "contents": "Ionic mechanism of 5-hydroxytryptamine induced hyperpolarization and inhibitory junctional potential in body wall muscle cells of Hirudo medicinalis. Five-hydroxytryptamine (5-HT) causes a hyperpolarization and increased conductance of the leech body wall muscle cell membrane. If 5-HT is applied in the absence of the Cl minus ion, the response appears as a depolarization, whereas if 5-HT is applied in the absence of the K+ ion, the response is a hyperpolarization. In both cases, the conductance of the muscle cell membrane is increased. Stimulation of the peripheral nerve to the body wall muscle produces a complex junctional potential in muscle cells. Exposing the muscle to d-tubocurarine (d-TC) eliminates the excitatory component (EJP) of the complex potential. The inhibitory potential (IJP) that remains has an equilibrium potential at approximately 65 mV. Furthermore, this IJP appears as a depolarization when the nerve is stimulated in the presence of d-TC and low CL minus, whereas this is not the case if the nerve is stimulated in the presence of d-TC and low K+. The drugs BOL-148 and cyproheptadine block the IJP's in the body wall muscle. These data are interpreted as indicating that 5-HT acts on leech body wall muscle cells by increasing the conductance to the Cl minus ion and that the IJP's caused by nerve stimulation are probably the result of 5-HT release at nerve terminals. As a final point, it has been shown that the inhibition by 5-HT of the spontaneous EJP's that occur on the leech body wall muscle results from an inhibition of central neurons and not from any direct effect on the muscle cell or on peripheral synapses."}
{"id": "PMID:2652", "title": "Cerebrospinal fluid lactate and lactate/pyruvate ratios in hydrocephalus.", "content": "Cerebral metabolism in 21 hydrocephalic patients was studied. Preoperative and postoperative specimens of cerebrospinal fluid (CSF) were obtained and the cerebral perfusion pressure (CPP) was calculated in each instance. The specimens of CSF were analyzed for lactate and pyruvate and the lactate/pyruvate (L/P) ratio was calculated for each sample. The L/P ratio, which reflects the redox state of the cell, was used to determine the extent of anaerobic metabolism. An inverse relationship was noted between CPP and lactate as well as the L/P ratio. In general, the level of anaerobic metabolism was decreased after insertion of a shunt.", "contents": "Cerebrospinal fluid lactate and lactate/pyruvate ratios in hydrocephalus. Cerebral metabolism in 21 hydrocephalic patients was studied. Preoperative and postoperative specimens of cerebrospinal fluid (CSF) were obtained and the cerebral perfusion pressure (CPP) was calculated in each instance. The specimens of CSF were analyzed for lactate and pyruvate and the lactate/pyruvate (L/P) ratio was calculated for each sample. The L/P ratio, which reflects the redox state of the cell, was used to determine the extent of anaerobic metabolism. An inverse relationship was noted between CPP and lactate as well as the L/P ratio. In general, the level of anaerobic metabolism was decreased after insertion of a shunt."}
{"id": "PMID:2653", "title": "Effects of hyperventilation, CO2, and CSF pressure on internal carotid blood flow in the baboon.", "content": "The combined effect upon cerebral blood flow (CBF) of an elevation of cerebrospinal fluid pressure (CSFP) and changes in respiratory CO2 was studied in nine baboons under chloralose anesthesia. The animals were mildly hyperventilated and provided with increasing amounts of CO2 in O2-air. Arterial CO2 tensions (PaCO2) increased from 17 to 58 mm Hg. Internal carotid blood flow (ICBF) was measured at normal CSFP and at hydrostatically maintained 50 mm Hg CSFP. It was found that: 1) end-tidal CO2 may be used as a substitute for arterial PaCO2 determinations; 2) this elevation of CSFP has little effect on ICBF during hypercapnia and normocapnia; however, 3) during hypocapnia the ICBF is reduced an additional 20% when CSFP is elevated; that is, ICBF is reduced 50% from normal when end-tidal CO2 is reduced to 2% at this elevated level of CSFP. Caution should be exercised during hyperventilation therapy particularly if the elevated CSFP or intracranial pressure (ICP) is not reduced to approach normal levels; in these conditions, the combination of decreasing PaCO2 and elevated ICP may reduce CBF below critical levels and thus lead to cerebral hypoxia.", "contents": "Effects of hyperventilation, CO2, and CSF pressure on internal carotid blood flow in the baboon. The combined effect upon cerebral blood flow (CBF) of an elevation of cerebrospinal fluid pressure (CSFP) and changes in respiratory CO2 was studied in nine baboons under chloralose anesthesia. The animals were mildly hyperventilated and provided with increasing amounts of CO2 in O2-air. Arterial CO2 tensions (PaCO2) increased from 17 to 58 mm Hg. Internal carotid blood flow (ICBF) was measured at normal CSFP and at hydrostatically maintained 50 mm Hg CSFP. It was found that: 1) end-tidal CO2 may be used as a substitute for arterial PaCO2 determinations; 2) this elevation of CSFP has little effect on ICBF during hypercapnia and normocapnia; however, 3) during hypocapnia the ICBF is reduced an additional 20% when CSFP is elevated; that is, ICBF is reduced 50% from normal when end-tidal CO2 is reduced to 2% at this elevated level of CSFP. Caution should be exercised during hyperventilation therapy particularly if the elevated CSFP or intracranial pressure (ICP) is not reduced to approach normal levels; in these conditions, the combination of decreasing PaCO2 and elevated ICP may reduce CBF below critical levels and thus lead to cerebral hypoxia."}
{"id": "PMID:2654", "title": "The effect of dietary vanadium on fatty acid and cholesterol synthesis and turnover in the chick.", "content": "Day-old male, broiler type chicks were used to study the effect of 100 ppm dietary vanadium on fatty acid and cholesterol synthesis and turnover in vivo. After feeding the experimental diets for 4 weeks body weight and liver weight of chicks fed 100 ppm vanadium were significantly less than those of the control chicks and liver total lipid and cholesterol tended to be slightly higher than the levels of the control chicks. [1-14C] Acetate was administered intravenously and the specific activities of plasma and liver total lipid, cholesterol and fatty acid were determined at 0.25, 0.50, 1.0, 4.0, 8.0 and 15.0 hours after the injection. Plasma total lipid and cholesterol were significantly higher than the levels in the control chicks. The rate of incorporation of [1-14C]acetate into plasma and liver total lipid, cholesterol and fatty acid was higher in chicks fed vanadium than the control group at any of the time being tested after the injection. There was a significant increase in the hepatic citrate cleavage enzyme activity among chicks fed 100 ppm vanadium, whereas, there was no significant change in acetate thiokinase activity. Turnover rate of plasma total lipid and fatty acid in vanadium fed chicks was lower than the control. The turnover rate of plasma cholesterol determined by administering [4-14C]cholesterol and periodically measuring the specific activity of plasma cholesterol was higher in chicks fed vanadium than in those fed the basal diet.", "contents": "The effect of dietary vanadium on fatty acid and cholesterol synthesis and turnover in the chick. Day-old male, broiler type chicks were used to study the effect of 100 ppm dietary vanadium on fatty acid and cholesterol synthesis and turnover in vivo. After feeding the experimental diets for 4 weeks body weight and liver weight of chicks fed 100 ppm vanadium were significantly less than those of the control chicks and liver total lipid and cholesterol tended to be slightly higher than the levels of the control chicks. [1-14C] Acetate was administered intravenously and the specific activities of plasma and liver total lipid, cholesterol and fatty acid were determined at 0.25, 0.50, 1.0, 4.0, 8.0 and 15.0 hours after the injection. Plasma total lipid and cholesterol were significantly higher than the levels in the control chicks. The rate of incorporation of [1-14C]acetate into plasma and liver total lipid, cholesterol and fatty acid was higher in chicks fed vanadium than the control group at any of the time being tested after the injection. There was a significant increase in the hepatic citrate cleavage enzyme activity among chicks fed 100 ppm vanadium, whereas, there was no significant change in acetate thiokinase activity. Turnover rate of plasma total lipid and fatty acid in vanadium fed chicks was lower than the control. The turnover rate of plasma cholesterol determined by administering [4-14C]cholesterol and periodically measuring the specific activity of plasma cholesterol was higher in chicks fed vanadium than in those fed the basal diet."}
{"id": "PMID:2655", "title": "Changes of pH-values during storage of fetal blood samples.", "content": "In recent years increased attention has been given to the degree of acidity of fetal blood during the course of labor or immediately after delivery. As it is not always possible to measure the blood pH immediately after sampling, it is important to know whether or not the pH is likely to change if the blood sample is stored for some time. 30 heparinized whole blood samples were collected from the umbilical artery of 30 newborn infants immediately after delivery and were stored at room temperature. pH -measurements were made every 5 minutes up to 80 minutes. In a second group the same number of samples were stored in a refrigator. pH-measurements were performed after 30 minutes and then every hour for up to 7 hours, and finally after 24 hours. The pHact-values did not change at room temperature (about 24 degrees C) for up to 25 minutes; pHqu40-values decreased initially more rapidly  but at 50 minutes the decrease was the same as in pHact-values namely 0.02 units. Afterwards the pHact-values decreased at a mena rate of about 0.03 units per hour and pHqu40-values at a mean rate of about 0.017 units per hour. If the storage temperature was lowered by refrigeration (about 6 degrees C) the pHact-values remained between 0 and -0.02 units for 6 hours and pHqu40-values for 3 hours. From these experiments it can be concluded that fetal blood samples must be kept in a refrigerator in order to inhibit autoxidation, if they have to be stored for longer than 50 minutes.", "contents": "Changes of pH-values during storage of fetal blood samples. In recent years increased attention has been given to the degree of acidity of fetal blood during the course of labor or immediately after delivery. As it is not always possible to measure the blood pH immediately after sampling, it is important to know whether or not the pH is likely to change if the blood sample is stored for some time. 30 heparinized whole blood samples were collected from the umbilical artery of 30 newborn infants immediately after delivery and were stored at room temperature. pH -measurements were made every 5 minutes up to 80 minutes. In a second group the same number of samples were stored in a refrigator. pH-measurements were performed after 30 minutes and then every hour for up to 7 hours, and finally after 24 hours. The pHact-values did not change at room temperature (about 24 degrees C) for up to 25 minutes; pHqu40-values decreased initially more rapidly  but at 50 minutes the decrease was the same as in pHact-values namely 0.02 units. Afterwards the pHact-values decreased at a mena rate of about 0.03 units per hour and pHqu40-values at a mean rate of about 0.017 units per hour. If the storage temperature was lowered by refrigeration (about 6 degrees C) the pHact-values remained between 0 and -0.02 units for 6 hours and pHqu40-values for 3 hours. From these experiments it can be concluded that fetal blood samples must be kept in a refrigerator in order to inhibit autoxidation, if they have to be stored for longer than 50 minutes."}
{"id": "PMID:2658", "title": "Inhibition of drug-induced anorexia in rats by methysergide.", "content": "Iproniazid was found to reduce food consumption in fasting rats. Combined treatment of iproniazid with tryptophan resulted in a significantly greater anorexic action whilst tryptophan alone had no effect on food consumption. Iproniazid treatment was associated with a significant increase in brain 5-hydroxytryptamine (5-HT) concentration but in association with tryptophan higher brain 5-HT concentrations were recorded. The anorexic action of the iproniazid-tryptophan combination was antagonized in a dose-dependent fashion by methysergide. Equivalent levels of anorexia induced by fenfluramine and mazindol were similarly antagonized by methysergide in a dose-related manner. The results suggest a common role of 5-HT in the inhibition of eating behaviour in fasting rats when anorexia is induced by iproniazid, fenfluramine or mazindol, sensitive to a specific 5-HT antagonist.", "contents": "Inhibition of drug-induced anorexia in rats by methysergide. Iproniazid was found to reduce food consumption in fasting rats. Combined treatment of iproniazid with tryptophan resulted in a significantly greater anorexic action whilst tryptophan alone had no effect on food consumption. Iproniazid treatment was associated with a significant increase in brain 5-hydroxytryptamine (5-HT) concentration but in association with tryptophan higher brain 5-HT concentrations were recorded. The anorexic action of the iproniazid-tryptophan combination was antagonized in a dose-dependent fashion by methysergide. Equivalent levels of anorexia induced by fenfluramine and mazindol were similarly antagonized by methysergide in a dose-related manner. The results suggest a common role of 5-HT in the inhibition of eating behaviour in fasting rats when anorexia is induced by iproniazid, fenfluramine or mazindol, sensitive to a specific 5-HT antagonist."}
{"id": "PMID:2659", "title": "Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency.", "content": "Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.", "contents": "Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency. Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine."}
{"id": "PMID:2660", "title": "The effect of an aldosterone antagonist on the protective action of carbenoxolone on the gastric mucosal barrier.", "content": "The effect of an aldosterone antagonist on the protective action of carbenoxolone sodium on the gastric mucosal barrier has been studied in three dogs with Heidenhain pouches. The net fluxes of hydrogen ion and sodium ion were measured before, during, and after contact with a 10 mM bile acid solution at pH 2, in pouches which had not been treated with drugs, in pouches treated with carbenoxolone sodium and in pouches treated with both carbenoxolone sodium and the aldosterone antagonist, spironolactone. Hydrogen ion back diffusion from, and sodium ion gain by the untreated pouch was increased by 10 mM bile acid solution. Addition to the pouches of either carbenoxolone sodium alone or carbenoxolone sodium and spironolactone reduced the hydrogen ion back diffusion after exposure to the bile acid solution. The spironolactone did not change the protective effect of carbenoxolone on the gastric mucosal barrier. Carbenoxolone did not change the increased sodium ion diffusion caused by bile.", "contents": "The effect of an aldosterone antagonist on the protective action of carbenoxolone on the gastric mucosal barrier. The effect of an aldosterone antagonist on the protective action of carbenoxolone sodium on the gastric mucosal barrier has been studied in three dogs with Heidenhain pouches. The net fluxes of hydrogen ion and sodium ion were measured before, during, and after contact with a 10 mM bile acid solution at pH 2, in pouches which had not been treated with drugs, in pouches treated with carbenoxolone sodium and in pouches treated with both carbenoxolone sodium and the aldosterone antagonist, spironolactone. Hydrogen ion back diffusion from, and sodium ion gain by the untreated pouch was increased by 10 mM bile acid solution. Addition to the pouches of either carbenoxolone sodium alone or carbenoxolone sodium and spironolactone reduced the hydrogen ion back diffusion after exposure to the bile acid solution. The spironolactone did not change the protective effect of carbenoxolone on the gastric mucosal barrier. Carbenoxolone did not change the increased sodium ion diffusion caused by bile."}
{"id": "PMID:2661", "title": "The quantification of kanamycin ototoxicity in the rat using conditioned tone discrimination.", "content": "Twelve male Lister hooded rats were conditioned to discriminate an 8 kHz tone (56.5 +/- 0.5 dB re 0.0002 dyne cm-2) and were subsequently injected subcutaneously with kanamycin (400 mg kg-1 day-1) for 28 days; during this time and for five weeks after dosage was stopped, the nature and extent of the resultant hearing deficits were studied. The animals' Preyer reflex thresholds were determined at intervals during the study. Only one rat was unaffected by the kanamycin dosage. The onset of hearing impairment (reduced discrimination performance), which was gradual in some rats and sudden in others, generally occurred during the fourth week of kanamycin dosage although the earliest onset was towards the end of the second week. In most animals the hearing impairment progressed after kanamycin was stopped and in one rat there was a latency between the end of drug dosage and onset of hearing impairment. Hearing impairment was irreversible in five rats. One rat, whose impairment was slight, recovered normal hearing. Some rats showed a reduced discrimination performance at a time when their Preyer reflex threshold showed no elevation suggesting that kanamycin, at least initially, caused a threshold elevation rather than reduced sensitivity to intense sounds.", "contents": "The quantification of kanamycin ototoxicity in the rat using conditioned tone discrimination. Twelve male Lister hooded rats were conditioned to discriminate an 8 kHz tone (56.5 +/- 0.5 dB re 0.0002 dyne cm-2) and were subsequently injected subcutaneously with kanamycin (400 mg kg-1 day-1) for 28 days; during this time and for five weeks after dosage was stopped, the nature and extent of the resultant hearing deficits were studied. The animals' Preyer reflex thresholds were determined at intervals during the study. Only one rat was unaffected by the kanamycin dosage. The onset of hearing impairment (reduced discrimination performance), which was gradual in some rats and sudden in others, generally occurred during the fourth week of kanamycin dosage although the earliest onset was towards the end of the second week. In most animals the hearing impairment progressed after kanamycin was stopped and in one rat there was a latency between the end of drug dosage and onset of hearing impairment. Hearing impairment was irreversible in five rats. One rat, whose impairment was slight, recovered normal hearing. Some rats showed a reduced discrimination performance at a time when their Preyer reflex threshold showed no elevation suggesting that kanamycin, at least initially, caused a threshold elevation rather than reduced sensitivity to intense sounds."}
{"id": "PMID:2662", "title": "The bioavailability in man of ICRF-159 a new oral antineoplastic agent.", "content": "The bioavailability of the antineoplastic agent, ICRF-159, has been examined in 12 patients receiving the drug in single and subdivided dose schedules in an attempt to account for the differences in toxicity found with the different schedules clinically. Recovery of radioactivity in the urine after single large doses (13.3-19.4 g) was 8.5 +/- 3.0% of the administered dose. After doses of 3.8-5.55 g recovery was 22.7 +/- 10.5% and after the same dose subdivided into 3 equal aliquots it was 52 +/- 8.7%. Unrecovered radioactivity was largely accounted for in the faeces. Plasma radioactivity levels in 2 patients after high and low dose were equivalent. Toxicity of the drug paralleled urinary recovery of radioactivity. It is concluded that schedule dependence of toxicity of ICRF-159 is at least partly due to bioavailability factors.", "contents": "The bioavailability in man of ICRF-159 a new oral antineoplastic agent. The bioavailability of the antineoplastic agent, ICRF-159, has been examined in 12 patients receiving the drug in single and subdivided dose schedules in an attempt to account for the differences in toxicity found with the different schedules clinically. Recovery of radioactivity in the urine after single large doses (13.3-19.4 g) was 8.5 +/- 3.0% of the administered dose. After doses of 3.8-5.55 g recovery was 22.7 +/- 10.5% and after the same dose subdivided into 3 equal aliquots it was 52 +/- 8.7%. Unrecovered radioactivity was largely accounted for in the faeces. Plasma radioactivity levels in 2 patients after high and low dose were equivalent. Toxicity of the drug paralleled urinary recovery of radioactivity. It is concluded that schedule dependence of toxicity of ICRF-159 is at least partly due to bioavailability factors."}
{"id": "PMID:2663", "title": "Cornea preparation for in vitro bio-pharmaceutical evaluation of ophthalmic dosage forms.", "content": "A system has been developed for a specific biopharmaceutical purpose: testing for ophthalmic preparations, the influence of formulation on drug transport through the cornea. The apparatus is a lucite cell, divided in two compartments by a clamped rabbit cornea. Physiological conditions are ensured by a supply of oxygenated perfusion medium. They are monitored by electrical conductivity and corneal thickness measurements. Reliability of the system was tested in a set of experiments.", "contents": "Cornea preparation for in vitro bio-pharmaceutical evaluation of ophthalmic dosage forms. A system has been developed for a specific biopharmaceutical purpose: testing for ophthalmic preparations, the influence of formulation on drug transport through the cornea. The apparatus is a lucite cell, divided in two compartments by a clamped rabbit cornea. Physiological conditions are ensured by a supply of oxygenated perfusion medium. They are monitored by electrical conductivity and corneal thickness measurements. Reliability of the system was tested in a set of experiments."}
{"id": "PMID:2664", "title": "A study of the human metabolism of secbutobarbitone.", "content": "The urinary excretion of secbutobarbitone (I) and its metabolites has been studied quantitatively using combined gas chromatography-mass spectrometry. After a single oral dose was given to healthy male volunteers, unchanged drug (5-9%), 2'-hydroxysecbutobarbitone (II, 1.7-3.2%), 2'-oxosecbutobarbitone (III, less than 1%), and the carboxylic acid (IV, 24-34%) were found. The kinetics of the excretion process were studied.", "contents": "A study of the human metabolism of secbutobarbitone. The urinary excretion of secbutobarbitone (I) and its metabolites has been studied quantitatively using combined gas chromatography-mass spectrometry. After a single oral dose was given to healthy male volunteers, unchanged drug (5-9%), 2'-hydroxysecbutobarbitone (II, 1.7-3.2%), 2'-oxosecbutobarbitone (III, less than 1%), and the carboxylic acid (IV, 24-34%) were found. The kinetics of the excretion process were studied."}
{"id": "PMID:2665", "title": "The identification and analysis of the metabolic products of mephentermine.", "content": "Phentermine (Ib), N-hydroxymephentermine (Ic) and N-hydroxyphentermine (Id) were identified as metabolic products after in vitro incubation of mephentermine (Ia) with rabbit liver microsomal fractions. Compounds Ia, Ib and Ic were also identified as excretion products in the urine of a human subject given a single dose of mephentermine (Ia) sulphate. Derivatization with acetic anhydride, trifluoroacetic anhydride and the trimethylsilyl donor reagent N,O-bis-(trimethylsilyl)-trifluoroacetamide (BSTFA) or hexamethyldisilazane (HMDS) were used for qualitative identification of the metabolic products Ib-Id by g.l.c.-mass spectrometry and for quantitative determination of Ia-Id after extraction from rabbit hepatic homogenates. The synthesis of N-hydroxymephentermine (Ic) and the properties of the metabolic products are reported.", "contents": "The identification and analysis of the metabolic products of mephentermine. Phentermine (Ib), N-hydroxymephentermine (Ic) and N-hydroxyphentermine (Id) were identified as metabolic products after in vitro incubation of mephentermine (Ia) with rabbit liver microsomal fractions. Compounds Ia, Ib and Ic were also identified as excretion products in the urine of a human subject given a single dose of mephentermine (Ia) sulphate. Derivatization with acetic anhydride, trifluoroacetic anhydride and the trimethylsilyl donor reagent N,O-bis-(trimethylsilyl)-trifluoroacetamide (BSTFA) or hexamethyldisilazane (HMDS) were used for qualitative identification of the metabolic products Ib-Id by g.l.c.-mass spectrometry and for quantitative determination of Ia-Id after extraction from rabbit hepatic homogenates. The synthesis of N-hydroxymephentermine (Ic) and the properties of the metabolic products are reported."}
{"id": "PMID:2666", "title": "A rapid g.l.c. procedure for the determination of codeine and norcodeine in biological fluids based on micro-phase extraction techniques.", "content": "Therapeutic serum concentrations of codeine can be virtually completely extracted and obtained sufficiently concentrated for g.c. measurement without distillation, by acid extraction of the drug from the initial crude organic extracts of alkalinized serum followed by a micro-phase back extraction step. The procedure has simplicity, rapidity and eliminates concentration by distillation and background interference. The method can be readily adapted for the seperate measurements of codeine and norcodeine and it can also be used for similar analysis of other body fluids.", "contents": "A rapid g.l.c. procedure for the determination of codeine and norcodeine in biological fluids based on micro-phase extraction techniques. Therapeutic serum concentrations of codeine can be virtually completely extracted and obtained sufficiently concentrated for g.c. measurement without distillation, by acid extraction of the drug from the initial crude organic extracts of alkalinized serum followed by a micro-phase back extraction step. The procedure has simplicity, rapidity and eliminates concentration by distillation and background interference. The method can be readily adapted for the seperate measurements of codeine and norcodeine and it can also be used for similar analysis of other body fluids."}
{"id": "PMID:2771", "title": "Plasma sodium concentration and sodium excretion in the anaesthetized dog.", "content": "1. The effect of acute alterations of plasma sodium concentration (PNa) on renal sodium excretion (UNaV) was investigated by three types of experiments on anaesthetized dogs: (a) A local increase in PNa at one kidney was produced by infusion of hypertonic saline directly into its artery while systemic levels of PNa were stabilized by haemodialysis. (b) Systemic levels of PNa were lowered by exchange transfusion of blood for an equal volume of salt-free dextran-in-dextrose solution. The results were contrasted with those observed after similar exchanges, but using dextran-in-saline solution. (c) The level of PNa was altered by varying the sodium concentration of a saline solution infused at a fixed rate either intravenously or into one renal artery. 2. All three types of experiment suggest a dependence of UNaV on PNa Analysis demonstrated that this relationship was not due to contemporary changes in: packed cell volume; plasma solids concentration; plasma potassium concentration; blood pressure or plasma hydrogen ion concentration. The distribution of these variables did not change with PNa except for plasma hydrogen ion concentration. Moreover, the relationship persisted when data were selected to exclude clearance periods in which the value for any variable had shifted past the group mean obtained before PNa was altered. 3. The fall in UNaV at low levels of PNa could be attributed to a fall in glomerular filtration rate (GFR), but the progressive rise in UNaV seen as PNa exceeded 150 m-mole 1(-1) occurred despite a fall in GFR and no apparent change in the mean filtered load of sodium. These results suggest that the increased sodium excretion accompanying raised levels of PNa is due to reduced tubular re-absorption of sodium.", "contents": "Plasma sodium concentration and sodium excretion in the anaesthetized dog. 1. The effect of acute alterations of plasma sodium concentration (PNa) on renal sodium excretion (UNaV) was investigated by three types of experiments on anaesthetized dogs: (a) A local increase in PNa at one kidney was produced by infusion of hypertonic saline directly into its artery while systemic levels of PNa were stabilized by haemodialysis. (b) Systemic levels of PNa were lowered by exchange transfusion of blood for an equal volume of salt-free dextran-in-dextrose solution. The results were contrasted with those observed after similar exchanges, but using dextran-in-saline solution. (c) The level of PNa was altered by varying the sodium concentration of a saline solution infused at a fixed rate either intravenously or into one renal artery. 2. All three types of experiment suggest a dependence of UNaV on PNa Analysis demonstrated that this relationship was not due to contemporary changes in: packed cell volume; plasma solids concentration; plasma potassium concentration; blood pressure or plasma hydrogen ion concentration. The distribution of these variables did not change with PNa except for plasma hydrogen ion concentration. Moreover, the relationship persisted when data were selected to exclude clearance periods in which the value for any variable had shifted past the group mean obtained before PNa was altered. 3. The fall in UNaV at low levels of PNa could be attributed to a fall in glomerular filtration rate (GFR), but the progressive rise in UNaV seen as PNa exceeded 150 m-mole 1(-1) occurred despite a fall in GFR and no apparent change in the mean filtered load of sodium. These results suggest that the increased sodium excretion accompanying raised levels of PNa is due to reduced tubular re-absorption of sodium."}
{"id": "PMID:2777", "title": "Synthesis of angiotensin II antagonists containing N- and O-methylated and other amino acid residues.", "content": "[1-N-Methylisoasparagine,8-isoleucine]- (I), [1-sarcosine,4-N-methyltyrosine,8-isoleucine]- (II), [1-sarcosine,5-N-methylisoleucine,8-isoleucine]- (III), [1-sarcosine,8-N-methylisoleucine]- (IV), [1-sarcosine8k-N-methylisoleucine,8-N-methylisoleucine]- (V), [1-sarcosine,8-O-methylthreonine]- (VI), [1-sarcosine,8-methionine]- (VII), and [1-sarcosine,8-serine]angiotensin II (VIII), synthesized by Merrifield's solid-phase procedure, possess respectively 0.8, 0.3, 0.5, 1.0, 0.0, 0.5, 3.7, and 0.7% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats). They caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized, ganglion-blocked rats) of 16.57, 9.80, 22.80, 32.00, 7.00, 15.06, 32.50, and 11.42 mmHg and showed secretory activity (isolated cat adrenal medulla) of 1.0, 0.1, 0.01, 0.1, less than 0.01, 0.1, less than 0.01, and 0.05% of angiotensin II. On isolated organs pA2 values (rabbit aortic strips) of 8.74, 7.44, 7.64, 7.85, 7.89, 8.76, 8.63, and 8.08, and pA2 values (cat adrenal medulla of 8.16, 9.16, 9.31, 8.00, 8.00, 7.00, 9.16, and 9.33 were obtained. Dose ratios (ratio of ED20 of angiotensin II during infusion of the antagonist and before infusion of the antagonist) in vagotomized, ganglion-blocked rats, infused at 250 ng/kg/min, were 33.43, 2.14, 3.26, 2.99, 0.62, 62.52, incalculable, and 11.15, respectively. The results obtained suggest that (a) analogs I and VI are potent antagonists of the pressor response of angiotensin II in normal rat, VI being the most potent antagonist thus far synthesized; (b) replacement of position 4 (Tyr) with MeTyr or position 5 and/or 8 (Ile) with Melle in [1-sarcosine,8-isoleucine]angiotensin II reduced the antagonist activity of this peptide (rabbit aortic strips and rats), indicating that steric hindrance imposed due to N-methylation in positions 4, 5, or 8 was not favorable in eliminating the initial pressor activity or prolonging the duration of action of [Sar1, Ile8]angiotensin II without reducing its antagonistic properties; (c) except II, none of the analogs showed any enhanced duration of action, suggesting that N-methylation in positions 5 or 8 did not afford protection against proteolytic enzymes; and (d) perfusion studies in cat adrenals indicated that all of these analogs are only very weak secretagogues. With the exception of [Sar1,Thr(ObetaMe)8]angiotensin II, which gave lower antagonistic properties, all other analogs had either similar antagonistic properties or were better antagonists in adrenal medulla than in smooth muscle.", "contents": "Synthesis of angiotensin II antagonists containing N- and O-methylated and other amino acid residues. [1-N-Methylisoasparagine,8-isoleucine]- (I), [1-sarcosine,4-N-methyltyrosine,8-isoleucine]- (II), [1-sarcosine,5-N-methylisoleucine,8-isoleucine]- (III), [1-sarcosine,8-N-methylisoleucine]- (IV), [1-sarcosine8k-N-methylisoleucine,8-N-methylisoleucine]- (V), [1-sarcosine,8-O-methylthreonine]- (VI), [1-sarcosine,8-methionine]- (VII), and [1-sarcosine,8-serine]angiotensin II (VIII), synthesized by Merrifield's solid-phase procedure, possess respectively 0.8, 0.3, 0.5, 1.0, 0.0, 0.5, 3.7, and 0.7% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats). They caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized, ganglion-blocked rats) of 16.57, 9.80, 22.80, 32.00, 7.00, 15.06, 32.50, and 11.42 mmHg and showed secretory activity (isolated cat adrenal medulla) of 1.0, 0.1, 0.01, 0.1, less than 0.01, 0.1, less than 0.01, and 0.05% of angiotensin II. On isolated organs pA2 values (rabbit aortic strips) of 8.74, 7.44, 7.64, 7.85, 7.89, 8.76, 8.63, and 8.08, and pA2 values (cat adrenal medulla of 8.16, 9.16, 9.31, 8.00, 8.00, 7.00, 9.16, and 9.33 were obtained. Dose ratios (ratio of ED20 of angiotensin II during infusion of the antagonist and before infusion of the antagonist) in vagotomized, ganglion-blocked rats, infused at 250 ng/kg/min, were 33.43, 2.14, 3.26, 2.99, 0.62, 62.52, incalculable, and 11.15, respectively. The results obtained suggest that (a) analogs I and VI are potent antagonists of the pressor response of angiotensin II in normal rat, VI being the most potent antagonist thus far synthesized; (b) replacement of position 4 (Tyr) with MeTyr or position 5 and/or 8 (Ile) with Melle in [1-sarcosine,8-isoleucine]angiotensin II reduced the antagonist activity of this peptide (rabbit aortic strips and rats), indicating that steric hindrance imposed due to N-methylation in positions 4, 5, or 8 was not favorable in eliminating the initial pressor activity or prolonging the duration of action of [Sar1, Ile8]angiotensin II without reducing its antagonistic properties; (c) except II, none of the analogs showed any enhanced duration of action, suggesting that N-methylation in positions 5 or 8 did not afford protection against proteolytic enzymes; and (d) perfusion studies in cat adrenals indicated that all of these analogs are only very weak secretagogues. With the exception of [Sar1,Thr(ObetaMe)8]angiotensin II, which gave lower antagonistic properties, all other analogs had either similar antagonistic properties or were better antagonists in adrenal medulla than in smooth muscle."}
{"id": "PMID:2778", "title": "Synthesis and enzymic activity of some novel xanthine oxidase inhibitors. 3-Substituted 5,7-dihydroxypyrazolo(1,5-alpha)pyrimidines.", "content": "A series of 3-substituted 5,7-dihydroxypyrazolo[1,5-alpha]pyrimidines containing various aromatic [phenyl- (3e), 3-pyridyl- (3f), p-bromophenyl- (3g), p-chlorophenyl- (3h), p-acetamidophenyl- (3i), p-tolyl- (3j), m-tolyl- (3k), 3,4-methylenedioxyphenyl- (3m), or naphthyl- (3n)] or nonaromatic [hydrogen- (3a), nitro- (3b), bromo- (3c), or chloro- (3d)] substituents in the 3 position was synthesized and tested as inhibitors of xanthine oxidase. The compounds (3a-m) were synthesized by condensation of the appropriate 3-amino-4-substituted pyrazole with diethyl malonate in alcoholic sodium methoxide and neutralization of the resulting enol sodium salts. As inhibitors of xanthine oxidase, 3e-n greater than 3a,c,d congruent to allopurinol greater than 3b. The 3-aryl-substituted compounds 3e-n were 30-160 times better xanthine oxidase inhibitors than allopurinol using hypoxanthine as substrate and 10-80 times better using xanthine as substrate, as evidenced by a comparison of Ki values. The inhibition by all compounds (3a-n) was totally reversible and of the noncompetitive or mixed type. A study of the pH dependence of xanthine oxidase inhibition by 3a,e,g and allopurinol indicated that the 3-aryl substituents facilitated binding to the enzyme. These and the above results show that the compounds reported here inhibit xanthine oxidase by a mechanism which is significantly different from that of allopurinol.", "contents": "Synthesis and enzymic activity of some novel xanthine oxidase inhibitors. 3-Substituted 5,7-dihydroxypyrazolo(1,5-alpha)pyrimidines. A series of 3-substituted 5,7-dihydroxypyrazolo[1,5-alpha]pyrimidines containing various aromatic [phenyl- (3e), 3-pyridyl- (3f), p-bromophenyl- (3g), p-chlorophenyl- (3h), p-acetamidophenyl- (3i), p-tolyl- (3j), m-tolyl- (3k), 3,4-methylenedioxyphenyl- (3m), or naphthyl- (3n)] or nonaromatic [hydrogen- (3a), nitro- (3b), bromo- (3c), or chloro- (3d)] substituents in the 3 position was synthesized and tested as inhibitors of xanthine oxidase. The compounds (3a-m) were synthesized by condensation of the appropriate 3-amino-4-substituted pyrazole with diethyl malonate in alcoholic sodium methoxide and neutralization of the resulting enol sodium salts. As inhibitors of xanthine oxidase, 3e-n greater than 3a,c,d congruent to allopurinol greater than 3b. The 3-aryl-substituted compounds 3e-n were 30-160 times better xanthine oxidase inhibitors than allopurinol using hypoxanthine as substrate and 10-80 times better using xanthine as substrate, as evidenced by a comparison of Ki values. The inhibition by all compounds (3a-n) was totally reversible and of the noncompetitive or mixed type. A study of the pH dependence of xanthine oxidase inhibition by 3a,e,g and allopurinol indicated that the 3-aryl substituents facilitated binding to the enzyme. These and the above results show that the compounds reported here inhibit xanthine oxidase by a mechanism which is significantly different from that of allopurinol."}
{"id": "PMID:2779", "title": "Immobilized glucuronosyltransferase for the synthesis of conjugates.", "content": "Partially purified rabbit liver UDPglucuronosyltransferase is immobilized on agarose by the cyanogen bromide activation method. Both soluble and matrix-bound enzyme preparations display very similar Km and pH optimum. The storage stability of the immobilized enzyme at 4 degrees is 5-10 times improved over the soluble preparations. The agarose-bound UDPglucuronosyltransferase is successfully used in the synthesis of p-nitrophenyl glucuronide in an overall yield of 50-70%. The matrix-bound enzyme is reusable over an extended period of time and offers an easy and convenient synthetic tool for various drug glucuronides.", "contents": "Immobilized glucuronosyltransferase for the synthesis of conjugates. Partially purified rabbit liver UDPglucuronosyltransferase is immobilized on agarose by the cyanogen bromide activation method. Both soluble and matrix-bound enzyme preparations display very similar Km and pH optimum. The storage stability of the immobilized enzyme at 4 degrees is 5-10 times improved over the soluble preparations. The agarose-bound UDPglucuronosyltransferase is successfully used in the synthesis of p-nitrophenyl glucuronide in an overall yield of 50-70%. The matrix-bound enzyme is reusable over an extended period of time and offers an easy and convenient synthetic tool for various drug glucuronides."}
{"id": "PMID:2780", "title": "The limits of informed consent.", "content": "The patient, a 59-year-old man, was referred to a psychiatric hospital with what appeared initially to be the signs and symptoms of mental disorder. In hospital a lesion of the brain was diagnosed and surgery was proposed to relieve the condition. The patient, however, during this and subsequent admissions to hospital, refused operation. His refusal to consent was regarded as valid as he seemed to have good insight into his condition. Finally, under section 26 of the Mental Health Act, he was treated surgically. Unfortunately the patient died six weeks later of intracranial haemorrhage. Three comments are made on this case - two by psychiatrists, Dr K Davison and Dr Ashley Robin, the other by a professor of Christian ethics, Professor F C Blackie. Both psychiatrists argue that when a patient's mind is affected by mental or organic illness to the degree that 'he cannot bring a rational and conscious mind' to the question of his treatment then the doctor, in consultation with the relatives, making clear to them the likely course of events if an operation is not performed, must take whatever is the proper course of action, in this case surgery. In this view, such an operation performed immediately the diagnosis was confirmed might not have been so complicated. Professor Blackie, commending 'the attempt to regard the patient as a responsible human being' with a 'moral right to be consulted on all aspects of treatment', questions in this patient the limits to which the appeal to reason was carried. He concludes that 'in this situation the advice and consent of the family must weigh more heavily than the statements of the patient'.", "contents": "The limits of informed consent. The patient, a 59-year-old man, was referred to a psychiatric hospital with what appeared initially to be the signs and symptoms of mental disorder. In hospital a lesion of the brain was diagnosed and surgery was proposed to relieve the condition. The patient, however, during this and subsequent admissions to hospital, refused operation. His refusal to consent was regarded as valid as he seemed to have good insight into his condition. Finally, under section 26 of the Mental Health Act, he was treated surgically. Unfortunately the patient died six weeks later of intracranial haemorrhage. Three comments are made on this case - two by psychiatrists, Dr K Davison and Dr Ashley Robin, the other by a professor of Christian ethics, Professor F C Blackie. Both psychiatrists argue that when a patient's mind is affected by mental or organic illness to the degree that 'he cannot bring a rational and conscious mind' to the question of his treatment then the doctor, in consultation with the relatives, making clear to them the likely course of events if an operation is not performed, must take whatever is the proper course of action, in this case surgery. In this view, such an operation performed immediately the diagnosis was confirmed might not have been so complicated. Professor Blackie, commending 'the attempt to regard the patient as a responsible human being' with a 'moral right to be consulted on all aspects of treatment', questions in this patient the limits to which the appeal to reason was carried. He concludes that 'in this situation the advice and consent of the family must weigh more heavily than the statements of the patient'."}
{"id": "PMID:2781", "title": "Calcium-potassium-stimulated net potassium efflux from human erythrocyte ghosts.", "content": "In the presence of 8 mM external Ca++, the K+ permeability of human red cell ghosts increases provided K+ is also present in the medium. This increase does not represent K+/K+ exchange but a stimulation of net K+ efflux. The stimulation is half-maximal at 0.7 +/- 0.15 mM (n=5). At concentrations above 4.0 mM, external K+ inhibits net K+ efflux. Similar stimulatory and inhibitory effects of external K were also observed in intact cells after exposure to Pb++ or to Ca++ in the presence of fluoride, iodoacetate plus adenosine, or propranolol, suggesting that a common K+ -activated K+ -specific transfer system may be involved under all of these various circumstances. Internal K+ also stimulates net K+ efflux from ghosts, but it is uncertain whether internal K+ is an absolute requirement for the K+ permeability increase. In contrast to external Na+ which slightly stimulates K+ efflux, internal Na+ inhibits. The inhibition by internal Na+ is abolished by sufficiently high concentrations of external K+, showing that K+ binding to the outer membrane surface and Na+ binding to the internal surface are mutually interdependent. In red cell ghosts the Ca++ -K+ -stimulated net K+ efflux increases with increasing pH until a plateau is reached between pH 7.2 and 8.0. In fluoride-poisoned intact cells, the Ca++-K+ stimulated flux passes through a maximum around pH 6.8. Neither internal nor external Mg++ interferes with the combined effects of Ca++ and K+. Similarly, external EDTA has no influence at concentrations which are far lower than the Ca++ concentration required to produce a maximal response. In contrast, low concentrations of internal EDTA prevent the permeability change.", "contents": "Calcium-potassium-stimulated net potassium efflux from human erythrocyte ghosts. In the presence of 8 mM external Ca++, the K+ permeability of human red cell ghosts increases provided K+ is also present in the medium. This increase does not represent K+/K+ exchange but a stimulation of net K+ efflux. The stimulation is half-maximal at 0.7 +/- 0.15 mM (n=5). At concentrations above 4.0 mM, external K+ inhibits net K+ efflux. Similar stimulatory and inhibitory effects of external K were also observed in intact cells after exposure to Pb++ or to Ca++ in the presence of fluoride, iodoacetate plus adenosine, or propranolol, suggesting that a common K+ -activated K+ -specific transfer system may be involved under all of these various circumstances. Internal K+ also stimulates net K+ efflux from ghosts, but it is uncertain whether internal K+ is an absolute requirement for the K+ permeability increase. In contrast to external Na+ which slightly stimulates K+ efflux, internal Na+ inhibits. The inhibition by internal Na+ is abolished by sufficiently high concentrations of external K+, showing that K+ binding to the outer membrane surface and Na+ binding to the internal surface are mutually interdependent. In red cell ghosts the Ca++ -K+ -stimulated net K+ efflux increases with increasing pH until a plateau is reached between pH 7.2 and 8.0. In fluoride-poisoned intact cells, the Ca++-K+ stimulated flux passes through a maximum around pH 6.8. Neither internal nor external Mg++ interferes with the combined effects of Ca++ and K+. Similarly, external EDTA has no influence at concentrations which are far lower than the Ca++ concentration required to produce a maximal response. In contrast, low concentrations of internal EDTA prevent the permeability change."}
{"id": "PMID:2782", "title": "Analog circuit of the Acetabularia membrane.", "content": "The high membrane potential of Acetabularia (Em=-170mV) is due to an electrogenic pump in parallel with the passive diffusion system (Ed=-80mV) which could be studied separately in the cold, when the pump is blocked. Electrical measurements under normal conditions show that the pump pathway consists of its electromotive force Ep with two elements P1 and P2 in series; P2 is shunted by a large capacitance (Cp=3mF cm-2). The nonlinear current-voltage relationship of P1 (light- and temperature-sensitive) could be determined separately; it reflects the properties of a carrier-mediated electrogenic pump. The value of Ep(-190 mV) indicates a stoichiometry of 2:1 between electrogenically transported charges and ATP. The electrical energy normally stored in Cp, compares well with the metabolic energy, stored in the ATP pool. The nonlinear current-voltage relationship of P2 (attributed to phosphorylating reactions) is also sensitive to light and temperature and is responsible for the region of negative conductance of the overall current-voltage relationship. The power of the pump (1 muW cm-2) amounts to some percent of the total energy turnover. The high Cl- fluxes (1 nmol cm-2 sec-1) and the electrical properties of the plasmalemma are not as closely related as assumed previously. For kinetic reasons, a direct and specific Cl- pathway between the vacuole and outside is postulated to exist.", "contents": "Analog circuit of the Acetabularia membrane. The high membrane potential of Acetabularia (Em=-170mV) is due to an electrogenic pump in parallel with the passive diffusion system (Ed=-80mV) which could be studied separately in the cold, when the pump is blocked. Electrical measurements under normal conditions show that the pump pathway consists of its electromotive force Ep with two elements P1 and P2 in series; P2 is shunted by a large capacitance (Cp=3mF cm-2). The nonlinear current-voltage relationship of P1 (light- and temperature-sensitive) could be determined separately; it reflects the properties of a carrier-mediated electrogenic pump. The value of Ep(-190 mV) indicates a stoichiometry of 2:1 between electrogenically transported charges and ATP. The electrical energy normally stored in Cp, compares well with the metabolic energy, stored in the ATP pool. The nonlinear current-voltage relationship of P2 (attributed to phosphorylating reactions) is also sensitive to light and temperature and is responsible for the region of negative conductance of the overall current-voltage relationship. The power of the pump (1 muW cm-2) amounts to some percent of the total energy turnover. The high Cl- fluxes (1 nmol cm-2 sec-1) and the electrical properties of the plasmalemma are not as closely related as assumed previously. For kinetic reasons, a direct and specific Cl- pathway between the vacuole and outside is postulated to exist."}
{"id": "PMID:2783", "title": "Nigericin-induced charge transfer across membranes.", "content": "The electric properties of the bilayer lecithin membranes have been studied in the presence of the antibiotic nigericin. When the antibiotic concentration is about 10(-7) ohm-1 cm-2. The potassium ion concentration gradient gives rise to a transmembrane potential of the order of 40 mV per 10-fold concentration gradient with the side of the higher potassium concentration negative. The transmembrane potential produced by the hydrogen ion concentration gradient is a function of the potassium ion concentration which is equal on both sides of the membrane. For low potassium ion concentrations the hydrogen potential has the expected polarity with the solution having higher concentration of protons negative. For potassium ion concentrations exceeding 0.03 M the hydrogen potential has the reverse polarity. This unexpected result cannot be accounted for in terms of the available simple hypotheses about the charge transport mechanism for nigericin in BLM. In order to account for the experimental results obtained, a theoretical approach has been developed based on the assumption that charge is transported across the membrane by nigericin dimers. The theoretical predicitons are in satisfactory agreement with the experimental results. The model also yields some predictions which may be verified in future experiments.", "contents": "Nigericin-induced charge transfer across membranes. The electric properties of the bilayer lecithin membranes have been studied in the presence of the antibiotic nigericin. When the antibiotic concentration is about 10(-7) ohm-1 cm-2. The potassium ion concentration gradient gives rise to a transmembrane potential of the order of 40 mV per 10-fold concentration gradient with the side of the higher potassium concentration negative. The transmembrane potential produced by the hydrogen ion concentration gradient is a function of the potassium ion concentration which is equal on both sides of the membrane. For low potassium ion concentrations the hydrogen potential has the expected polarity with the solution having higher concentration of protons negative. For potassium ion concentrations exceeding 0.03 M the hydrogen potential has the reverse polarity. This unexpected result cannot be accounted for in terms of the available simple hypotheses about the charge transport mechanism for nigericin in BLM. In order to account for the experimental results obtained, a theoretical approach has been developed based on the assumption that charge is transported across the membrane by nigericin dimers. The theoretical predicitons are in satisfactory agreement with the experimental results. The model also yields some predictions which may be verified in future experiments."}
{"id": "PMID:2786", "title": "Reactions of aminomalononitrile with electrophiles.", "content": "Aminomalononitrile (HCN trimer) reacts with electrophiles such as aldehydes and acrylonitrile under very mild conditions of temperature and pH to produce intermediates which, after acid hydrolysis, yield amino acids. The following amino acids have been identified and quantitated: glycine, D, L-erythro- and D, L-threo-beta - hydroxyaspartic acids, D, L glutamic acid, and D, L-threonine and allo-threonine. The mechanism of their formation and the possible significance of these reactions in prebiotic syntheses are discussed.", "contents": "Reactions of aminomalononitrile with electrophiles. Aminomalononitrile (HCN trimer) reacts with electrophiles such as aldehydes and acrylonitrile under very mild conditions of temperature and pH to produce intermediates which, after acid hydrolysis, yield amino acids. The following amino acids have been identified and quantitated: glycine, D, L-erythro- and D, L-threo-beta - hydroxyaspartic acids, D, L glutamic acid, and D, L-threonine and allo-threonine. The mechanism of their formation and the possible significance of these reactions in prebiotic syntheses are discussed."}
{"id": "PMID:2800", "title": "[Diagnosis and therapy of primary defects of immunity (author's transl)].", "content": "Immunological responses are divided into those mediated by humoral antibody (B-Cells) and those by cells (T-Cells). Both depend upon the activity of small lymphocytes which become thymus or bursa analogue dependent during embryonic development. Primary immundeficiencies are therefor defects of lymphocytes attributed in most cases to gene defects. Early diagnosis is the necessary prerequisit for possible treatment. Tests for assessing the cellular immune status are: skin testes and in vitro tests. Clinical syndroms are: lymphocytopenia, hypoplasia, deficiency of lymphocytes in lymphatic tissues normal cortical germinal centres. Recurrent infections with viruses, candida or pneumocystis carinii are common. Tests for assesing the humoral immune status are: measurement of immunglobulin levels in serum, isohaemagglutinins, tests for antibody formation following active immunization, in vitro tests. Clinical syndroms are: no germinal centres in lymphnodes, no plasma cells. Recurrent bacterial infections. Treatment of B-cell deficiencies: immunglobulin replacement therapy. Treatment of T-cell deficiencies by grafting of thymus transplants. Combined immune deficiencies are treated with bone marrow transplants from matched donors. For bone marrow transplantation germfree state seems to be the ideal situation to protect the patient against infection before the therapeutic maneuver and for prevention of graft versus host reaction in the posttransplantation period.", "contents": "[Diagnosis and therapy of primary defects of immunity (author's transl)]. Immunological responses are divided into those mediated by humoral antibody (B-Cells) and those by cells (T-Cells). Both depend upon the activity of small lymphocytes which become thymus or bursa analogue dependent during embryonic development. Primary immundeficiencies are therefor defects of lymphocytes attributed in most cases to gene defects. Early diagnosis is the necessary prerequisit for possible treatment. Tests for assessing the cellular immune status are: skin testes and in vitro tests. Clinical syndroms are: lymphocytopenia, hypoplasia, deficiency of lymphocytes in lymphatic tissues normal cortical germinal centres. Recurrent infections with viruses, candida or pneumocystis carinii are common. Tests for assesing the humoral immune status are: measurement of immunglobulin levels in serum, isohaemagglutinins, tests for antibody formation following active immunization, in vitro tests. Clinical syndroms are: no germinal centres in lymphnodes, no plasma cells. Recurrent bacterial infections. Treatment of B-cell deficiencies: immunglobulin replacement therapy. Treatment of T-cell deficiencies by grafting of thymus transplants. Combined immune deficiencies are treated with bone marrow transplants from matched donors. For bone marrow transplantation germfree state seems to be the ideal situation to protect the patient against infection before the therapeutic maneuver and for prevention of graft versus host reaction in the posttransplantation period."}
{"id": "PMID:2802", "title": "[Effect of the chronic action of small doses of ionizing radiation of the excretion of gaseous metabolic products in albino rats].", "content": "White rats were kept in sealed chambers for 3 months and were exposed to chronic gamma-irradiation (100 mur/day). The effect of the exposure on the excretion of some metabolites--ammonia, acetone, carbon monoxide, phenol and organic substances measured by their oxidability--was studied. Under the influence of low doses of gamma-irradiation the excretion of acetone and organic substances decreased, whereas that of carbon monoxide, phenol and ammonia increased. Possible mechanisms responsible for these changes are discussed.", "contents": "[Effect of the chronic action of small doses of ionizing radiation of the excretion of gaseous metabolic products in albino rats]. White rats were kept in sealed chambers for 3 months and were exposed to chronic gamma-irradiation (100 mur/day). The effect of the exposure on the excretion of some metabolites--ammonia, acetone, carbon monoxide, phenol and organic substances measured by their oxidability--was studied. Under the influence of low doses of gamma-irradiation the excretion of acetone and organic substances decreased, whereas that of carbon monoxide, phenol and ammonia increased. Possible mechanisms responsible for these changes are discussed."}
{"id": "PMID:2803", "title": "[Effect of hyperoxia and hypokinesia on the formation and excretion of gaseous metabolic products in rats].", "content": "It has been shown experimentally that a 30-day exposure of white rats to hypokinesia and moderate hyperoxia decreases elimination of ammonia and increases the formation and release into an enclosed atmosphere of carbon monoxide, aldehydes and ketones. The level of metabolism of prophyrin and nitrogen containing compounds as well as of fats and carbohydrates is higher during a combined effect of hypokinesia and moderate hyperoxia than during their separate influences.", "contents": "[Effect of hyperoxia and hypokinesia on the formation and excretion of gaseous metabolic products in rats]. It has been shown experimentally that a 30-day exposure of white rats to hypokinesia and moderate hyperoxia decreases elimination of ammonia and increases the formation and release into an enclosed atmosphere of carbon monoxide, aldehydes and ketones. The level of metabolism of prophyrin and nitrogen containing compounds as well as of fats and carbohydrates is higher during a combined effect of hypokinesia and moderate hyperoxia than during their separate influences."}
{"id": "PMID:2804", "title": "[Sorption method of water regeneration for cosmonaut personal hygiene].", "content": "The paper describes sanitary-hygienic and technological investigations aimed at development of the sorption method of water reclamation for personal hygiene needs of cosmonauts from wash water. Catamine-AB was used as a detergent with bactericidal properties. Manned experiments helped to identify the conditions that provided an adequate cleaning of skin and simultaneous sterilization of wash water. The technology of wash water purification was developed, proper sorbents were selected and recommended values of their use were established.", "contents": "[Sorption method of water regeneration for cosmonaut personal hygiene]. The paper describes sanitary-hygienic and technological investigations aimed at development of the sorption method of water reclamation for personal hygiene needs of cosmonauts from wash water. Catamine-AB was used as a detergent with bactericidal properties. Manned experiments helped to identify the conditions that provided an adequate cleaning of skin and simultaneous sterilization of wash water. The technology of wash water purification was developed, proper sorbents were selected and recommended values of their use were established."}
{"id": "PMID:2808", "title": "Plasma glucose in miniature swine infused with ethanol and fructose.", "content": "Hypoglycemia resulting from intragastric infusion of ethanol in miniature swine was counteracted by simultaneous infusion of fructose. The magnitude and time of peak plasma ethanol concentrations were functions of the quantity of ethanol or ethanol and fructose.", "contents": "Plasma glucose in miniature swine infused with ethanol and fructose. Hypoglycemia resulting from intragastric infusion of ethanol in miniature swine was counteracted by simultaneous infusion of fructose. The magnitude and time of peak plasma ethanol concentrations were functions of the quantity of ethanol or ethanol and fructose."}
{"id": "PMID:2806", "title": "[Effect of a magnetic field on Escherichia coli].", "content": "The decontaminating effect of the pulsing magnetic field on the E. coli infected reclaimed water was studied on two installations. The magnetic field intensity was 500 and 1000-1500 ersted and the microbial load was 1, 10 and 100 thous. microbial units per 1 ml. It was found that the magnetic treatment of water had a noticeable bactericidal effect. This indicated that the method can be used for decontamination of reclaimed water.", "contents": "[Effect of a magnetic field on Escherichia coli]. The decontaminating effect of the pulsing magnetic field on the E. coli infected reclaimed water was studied on two installations. The magnetic field intensity was 500 and 1000-1500 ersted and the microbial load was 1, 10 and 100 thous. microbial units per 1 ml. It was found that the magnetic treatment of water had a noticeable bactericidal effect. This indicated that the method can be used for decontamination of reclaimed water."}
{"id": "PMID:2809", "title": "Dietary caffeine and alcohol consumption by rats.", "content": "The alcohol consumption of malnourished rats increased slowly but substantially during a 4-week period in which caffeine was added to their marginally adequate diet. Consumption fell to precaffeine levels as soon as caffeine was withdrawn.", "contents": "Dietary caffeine and alcohol consumption by rats. The alcohol consumption of malnourished rats increased slowly but substantially during a 4-week period in which caffeine was added to their marginally adequate diet. Consumption fell to precaffeine levels as soon as caffeine was withdrawn."}
{"id": "PMID:2810", "title": "Effect of taurine on ethanol-induced sleeping time in mice.", "content": "The CNS-depressant effect of ethanol was markedly reduced in mice by simultaneous intraperitoneal injection of taurine.", "contents": "Effect of taurine on ethanol-induced sleeping time in mice. The CNS-depressant effect of ethanol was markedly reduced in mice by simultaneous intraperitoneal injection of taurine."}
{"id": "PMID:2807", "title": "[Urine conservation by surface-active agents].", "content": "The antibacterial activity of surface-active substances -- catamine-AB, catapine B-300, GIPH-200 and Tego-51 was measured on the E. coli and Staphylococcus aureus cultures and anthracoid spores. The purpose of the measurements was to explore the use of the substances as urine conserving agents. Catamine-AB showed the highest antibacterial activity. Anthracoid spores exhibited the highest resistance to the substances; staphylococci were less resistant than E. coli. Investigations of the effectiveness of urine conservation demonstrated that catamine-AB at a concentration of 0.1% killed all Staph. aureus and E. coli. Therefore, it can be recommended as a urine conserving agent.", "contents": "[Urine conservation by surface-active agents]. The antibacterial activity of surface-active substances -- catamine-AB, catapine B-300, GIPH-200 and Tego-51 was measured on the E. coli and Staphylococcus aureus cultures and anthracoid spores. The purpose of the measurements was to explore the use of the substances as urine conserving agents. Catamine-AB showed the highest antibacterial activity. Anthracoid spores exhibited the highest resistance to the substances; staphylococci were less resistant than E. coli. Investigations of the effectiveness of urine conservation demonstrated that catamine-AB at a concentration of 0.1% killed all Staph. aureus and E. coli. Therefore, it can be recommended as a urine conserving agent."}
{"id": "PMID:2811", "title": "Blood alcohol level discrimination by nonalcoholics. The role of internal and external cues.", "content": "Men were trained to estimate their blood alcohol levels, after drinks of different strengths, by means of internal or external cues or both. All groups improved in estimation accuracy but the type of training made no difference.", "contents": "Blood alcohol level discrimination by nonalcoholics. The role of internal and external cues. Men were trained to estimate their blood alcohol levels, after drinks of different strengths, by means of internal or external cues or both. All groups improved in estimation accuracy but the type of training made no difference."}
{"id": "PMID:2812", "title": "Alcohol and backward masking of visual information.", "content": "Alcohol increased the time necessary to transfer information from the initial sensory information storage system into the short-term memory system.", "contents": "Alcohol and backward masking of visual information. Alcohol increased the time necessary to transfer information from the initial sensory information storage system into the short-term memory system."}
{"id": "PMID:2813", "title": "Recovery of verbal short-term memory in alcoholics.", "content": "When given a short-term memory distractor test on the day after admission to the hospital in an intoxicated state, the performance of older alcoholic patients was significantly worse than that of younger alcoholics and on a par with that of alcoholic Korsakoff patients. One month later, however, the older patients' performance was comparable to that of the other alcoholics.", "contents": "Recovery of verbal short-term memory in alcoholics. When given a short-term memory distractor test on the day after admission to the hospital in an intoxicated state, the performance of older alcoholic patients was significantly worse than that of younger alcoholics and on a par with that of alcoholic Korsakoff patients. One month later, however, the older patients' performance was comparable to that of the other alcoholics."}
{"id": "PMID:2814", "title": "Group therapy and changes in the self-concept of alcoholics.", "content": "One group of alcoholics received closed-group encounter therapy, and another, open elective group therapy. The closed-group encounter therapy was superior in elevating self-concept.", "contents": "Group therapy and changes in the self-concept of alcoholics. One group of alcoholics received closed-group encounter therapy, and another, open elective group therapy. The closed-group encounter therapy was superior in elevating self-concept."}
{"id": "PMID:2815", "title": "Alcoholism, hopelessness and suicidal behavior.", "content": "A study of alcoholic and nonalcoholic suicide attempters indicated that hopelessness was the key determinant of suicidal intent in both groups.", "contents": "Alcoholism, hopelessness and suicidal behavior. A study of alcoholic and nonalcoholic suicide attempters indicated that hopelessness was the key determinant of suicidal intent in both groups."}
{"id": "PMID:2816", "title": "An application of anomy theory to the study of alcoholism.", "content": "In a study of 442 alcoholics, a positive relationship between the development of anomy and the development of alcoholism was found.", "contents": "An application of anomy theory to the study of alcoholism. In a study of 442 alcoholics, a positive relationship between the development of anomy and the development of alcoholism was found."}
{"id": "PMID:2817", "title": "Drinking behavior in laboratory and barroom settings.", "content": "Barroom patrons consumed their drinks in significantly less time and with fewer sips than subjects observed in a laboratory. The former most often drank beer while the latter preferred mixed drinks.", "contents": "Drinking behavior in laboratory and barroom settings. Barroom patrons consumed their drinks in significantly less time and with fewer sips than subjects observed in a laboratory. The former most often drank beer while the latter preferred mixed drinks."}
{"id": "PMID:2818", "title": "Effect of role empathy on human figures drawn by women alcoholics.", "content": "Drawings by women alcoholics of the self, a murderer, the murderer's victim and victim's parent revealed conscious and unconscious identification with the depicted roles.", "contents": "Effect of role empathy on human figures drawn by women alcoholics. Drawings by women alcoholics of the self, a murderer, the murderer's victim and victim's parent revealed conscious and unconscious identification with the depicted roles."}
{"id": "PMID:2819", "title": "The Cornell Medical Index as an adjunct to paraprofessional evaluation of alcohol addiction.", "content": "The Cornell Medical Index may prove a significant aid to paraprofessional personnel in recognizing alcoholics in need of medical attention.", "contents": "The Cornell Medical Index as an adjunct to paraprofessional evaluation of alcohol addiction. The Cornell Medical Index may prove a significant aid to paraprofessional personnel in recognizing alcoholics in need of medical attention."}
{"id": "PMID:2820", "title": "Surgical management of severe aortic coarctation and interrupted aortic arch in neonates.", "content": "Forty-four infants, 2 to 90 days of age, with severe obstructive lesions of the aortic arch, underwent emergency surgical correction between Jan. 1, 1966, and April 1, 1975. The typical clinical presentation was severe congestive heart failure and acidemia. Resection of an aortic coarctation with end-to-end anastomosis was performed in 31 patients. Eight (26 per cent) died after the operation. Since 1969, the mortality rate has been reduced to 14 per cent (3 of 22 patients) even though the incidence of major associated cardiac lesions has remained essentially constant (56 per cent from 1966 through 1969, 64 per cent from 1970 through March, 1975). This suggests that the higher survival rate has resulted from improved surgical techniques and postoperative care. The mortality rate in the infants operated upon during the second and third months of life was twice as high as that in those operated upon before the age of 1 month. Eight patients with Type A interrupted aortic arch were operated upon and 5 survived. Five patients with Type B aortic arch were operated upon and 3 survived.", "contents": "Surgical management of severe aortic coarctation and interrupted aortic arch in neonates. Forty-four infants, 2 to 90 days of age, with severe obstructive lesions of the aortic arch, underwent emergency surgical correction between Jan. 1, 1966, and April 1, 1975. The typical clinical presentation was severe congestive heart failure and acidemia. Resection of an aortic coarctation with end-to-end anastomosis was performed in 31 patients. Eight (26 per cent) died after the operation. Since 1969, the mortality rate has been reduced to 14 per cent (3 of 22 patients) even though the incidence of major associated cardiac lesions has remained essentially constant (56 per cent from 1966 through 1969, 64 per cent from 1970 through March, 1975). This suggests that the higher survival rate has resulted from improved surgical techniques and postoperative care. The mortality rate in the infants operated upon during the second and third months of life was twice as high as that in those operated upon before the age of 1 month. Eight patients with Type A interrupted aortic arch were operated upon and 5 survived. Five patients with Type B aortic arch were operated upon and 3 survived."}
{"id": "PMID:2821", "title": "Pharmacological analysis of the adrenergic control of the cerebral circulation.", "content": "The adrenergic control of the cerebral circulation was subjected to pharmacological analysis. The status of the cerebral circulation was assessed using radioisotope, electromagnetic and resistographic methods. EEG, ECG and arterial pressure were recorded. The acid-base equilibrium and oxygen tension were measured in the arterial blood and cerebrospinal fluid. The experiments showed that the sympathetic innervation plays an important role in controlling cerebral circulation and in the development of cerebrovascular disorders. This was indicated by the constriction of intracranial arteries induced by noradrenaline, stimulation of sympathetic nerves, reflex sympathetic activations and the effect of potassium chloride on the centrol nervous system. The pharmacological study demonstrated that constriction of the intracranial vessels is brought about by an activation of the sympatho-adrenal system which is mediated via alpha-adrenoreceptors of cerebral blood vessels.", "contents": "Pharmacological analysis of the adrenergic control of the cerebral circulation. The adrenergic control of the cerebral circulation was subjected to pharmacological analysis. The status of the cerebral circulation was assessed using radioisotope, electromagnetic and resistographic methods. EEG, ECG and arterial pressure were recorded. The acid-base equilibrium and oxygen tension were measured in the arterial blood and cerebrospinal fluid. The experiments showed that the sympathetic innervation plays an important role in controlling cerebral circulation and in the development of cerebrovascular disorders. This was indicated by the constriction of intracranial arteries induced by noradrenaline, stimulation of sympathetic nerves, reflex sympathetic activations and the effect of potassium chloride on the centrol nervous system. The pharmacological study demonstrated that constriction of the intracranial vessels is brought about by an activation of the sympatho-adrenal system which is mediated via alpha-adrenoreceptors of cerebral blood vessels."}
{"id": "PMID:2832", "title": "Cholesterol and fatty acid synthesis in swine.", "content": "In incubation studies with swine tissue slices, acetate-1-14C or glucose-U-14C as substrates were incorporated more readily into fatty acids and cholesterol in adipose tissue than other tissues tested. Cholesterol and fatty acid synthesizing acitivity was substantial in the small intestine. When acetate was available, liver, small intestine, and adipose tissue were important sites for cholesterol synthesis. Heart and aortic tissue had marginal levels of cholesterol synthesizing ability. Lipogenesis in adult swine liver, heart, and aortic tissue was extremely low. As in tissue slices, incorporation of acetyl-1-14C CoA into fatty acids by adipose homogenates indicated high lipogenic activity. Subcellular fractionations of heart and aortic tissue indicated that the heart microsomal fraction had the highest lipogenic activity as measured by the incroporation of acetyl-4-14C CoA into fatty acids. In adult swine adipose tissue, the incorporation of glucose-U-14C into fatty acid was higher than its incorporation into glyceride-glycerol. The synthesis of glyceride-glycerol from glucose-U-14C or acetate-1-14C in liver was higher than for fatty acid synthesis. The acitivity of acetyl CoA carboxylase, fatty acid synthetase, citrate cleavage enzyme, nicotinamide adenine dinucleotide phosphat-malate dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase was considerably higher in adipose tissue than in other tissues tested, paralleling its high lipogenic capacity.", "contents": "Cholesterol and fatty acid synthesis in swine. In incubation studies with swine tissue slices, acetate-1-14C or glucose-U-14C as substrates were incorporated more readily into fatty acids and cholesterol in adipose tissue than other tissues tested. Cholesterol and fatty acid synthesizing acitivity was substantial in the small intestine. When acetate was available, liver, small intestine, and adipose tissue were important sites for cholesterol synthesis. Heart and aortic tissue had marginal levels of cholesterol synthesizing ability. Lipogenesis in adult swine liver, heart, and aortic tissue was extremely low. As in tissue slices, incorporation of acetyl-1-14C CoA into fatty acids by adipose homogenates indicated high lipogenic activity. Subcellular fractionations of heart and aortic tissue indicated that the heart microsomal fraction had the highest lipogenic activity as measured by the incroporation of acetyl-4-14C CoA into fatty acids. In adult swine adipose tissue, the incorporation of glucose-U-14C into fatty acid was higher than its incorporation into glyceride-glycerol. The synthesis of glyceride-glycerol from glucose-U-14C or acetate-1-14C in liver was higher than for fatty acid synthesis. The acitivity of acetyl CoA carboxylase, fatty acid synthetase, citrate cleavage enzyme, nicotinamide adenine dinucleotide phosphat-malate dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase was considerably higher in adipose tissue than in other tissues tested, paralleling its high lipogenic capacity."}
{"id": "PMID:2834", "title": "Insulin receptors of skeletal muscle: specific insulin binding sites and demonstration of decreased numbers of sites in obese rats.", "content": "A membrane preparation was obtained from rat striated muscle. The preparation used has been shown to contain plasma membranes by electron microscopy as well as by enrichment in specific activity of both a plasma membrane enzyme \"marker\" (5'-nucleotidase) and cell surface 125I-incorporated radioactivity. The characteristics of 125I-insulin binding to this striated muscle preparation were studied, and it was found that 125I-insulin readily and specifically binds to this membrane preparation. The binding reaction was time, pH, and temperature dependent with optimal steady-state binding conditions occurring at 20 degrees C and at pH 7.6. Under these conditions (20 degrees C, pH 7.6) skeletal muscle plasma membranes displayed little ability to degrade insulin. Binding of 125I-insulin was readily inhibited at physiologic concentrations of unlabeled insulin and the specificity of this receptor for insulin was demonstrated by finding that high concentrations of glucagon, b-LH, b-FSH, p-PRL, hCG, TSH, and HGH were without effect on 125I-insulin binding and that insulin analogues inhibited binding in proportion to their biologic activity. When membranes from older, fatter rats were compared to membranes from younger, lean animals, 5'-nucleotidase specific activity and insulin degrading activity were found to be comparable. On the other hand, insulin binding to membrane receptors was decreased 30%-40% in the older, fatter animals. Thus, these studies indicate that (1) specific insulin receptors exist in skeletal muscle plasma membranes, and (2) membranes from older, fatter rats have fewer receptors than those from younger, lean animals.", "contents": "Insulin receptors of skeletal muscle: specific insulin binding sites and demonstration of decreased numbers of sites in obese rats. A membrane preparation was obtained from rat striated muscle. The preparation used has been shown to contain plasma membranes by electron microscopy as well as by enrichment in specific activity of both a plasma membrane enzyme \"marker\" (5'-nucleotidase) and cell surface 125I-incorporated radioactivity. The characteristics of 125I-insulin binding to this striated muscle preparation were studied, and it was found that 125I-insulin readily and specifically binds to this membrane preparation. The binding reaction was time, pH, and temperature dependent with optimal steady-state binding conditions occurring at 20 degrees C and at pH 7.6. Under these conditions (20 degrees C, pH 7.6) skeletal muscle plasma membranes displayed little ability to degrade insulin. Binding of 125I-insulin was readily inhibited at physiologic concentrations of unlabeled insulin and the specificity of this receptor for insulin was demonstrated by finding that high concentrations of glucagon, b-LH, b-FSH, p-PRL, hCG, TSH, and HGH were without effect on 125I-insulin binding and that insulin analogues inhibited binding in proportion to their biologic activity. When membranes from older, fatter rats were compared to membranes from younger, lean animals, 5'-nucleotidase specific activity and insulin degrading activity were found to be comparable. On the other hand, insulin binding to membrane receptors was decreased 30%-40% in the older, fatter animals. Thus, these studies indicate that (1) specific insulin receptors exist in skeletal muscle plasma membranes, and (2) membranes from older, fatter rats have fewer receptors than those from younger, lean animals."}
{"id": "PMID:2835", "title": "The role of potassium in the control of ammonium excretion during starvation.", "content": "Administration of KC1 0.5 mmol/kg/day to subjects undergoin prolonged starvation reduced daily urinary ammonium and beta-hydroxybutyrate excretion by one-third. These changes were accompanied by an improvement in potassium balance and an increased rate of chloride excretion. A similar fall in ammonium excretion occurred in a second group of subjects after administration of KHCO3 0.5 mmol/kg/day. Ketone body and bicarbonate excretion remained unchanged in this group while potassium balance improved. In both the first and second groups urine pH fell significantly as the rate of excretion of urinary buffer (ammonium) decreased. When the dose of KHCO3 was increased to 1.5-2.0 mmol/kg/day in fasting subjects, the urine was alkalinized, and ammonium excretion fell to negligible levels, resulting in nitrogen sparing of 2.0 g/day. The results indicate that one-half of the increase in ammonium excretion observed in starvation is due to potassium deficiency. Nitrogen wastage caused by losses of urinary ammonium during starvation can be virtually eliminated by potassium supplementation and urinary alkalinization. The decrease in beta-hydroxybutyrate excretion after potassium chloride administration was not caused by a fall in the rate of nonionic diffusion of this organic acid related to the reduction in urine pH. The reason for the fall in beta-hydroxybutyrate excretion is not apparent, though it was associated with an increase in chloride excretion.", "contents": "The role of potassium in the control of ammonium excretion during starvation. Administration of KC1 0.5 mmol/kg/day to subjects undergoin prolonged starvation reduced daily urinary ammonium and beta-hydroxybutyrate excretion by one-third. These changes were accompanied by an improvement in potassium balance and an increased rate of chloride excretion. A similar fall in ammonium excretion occurred in a second group of subjects after administration of KHCO3 0.5 mmol/kg/day. Ketone body and bicarbonate excretion remained unchanged in this group while potassium balance improved. In both the first and second groups urine pH fell significantly as the rate of excretion of urinary buffer (ammonium) decreased. When the dose of KHCO3 was increased to 1.5-2.0 mmol/kg/day in fasting subjects, the urine was alkalinized, and ammonium excretion fell to negligible levels, resulting in nitrogen sparing of 2.0 g/day. The results indicate that one-half of the increase in ammonium excretion observed in starvation is due to potassium deficiency. Nitrogen wastage caused by losses of urinary ammonium during starvation can be virtually eliminated by potassium supplementation and urinary alkalinization. The decrease in beta-hydroxybutyrate excretion after potassium chloride administration was not caused by a fall in the rate of nonionic diffusion of this organic acid related to the reduction in urine pH. The reason for the fall in beta-hydroxybutyrate excretion is not apparent, though it was associated with an increase in chloride excretion."}
{"id": "PMID:2836", "title": "Lactic acidosis: an experimental model.", "content": "A model of spontaneous lactic acidosis was developed in alloxan diabetic rabbits by infusing intravenously beta-hydroxybutyric acid followed by a continuous infusion of NaHCO3. In half of the animals, the arterial lactate/pyruvate ratio rose from 2.5 mM/0.19mM to 20.4 mM/0.28 mM, and arterial pH fell to 7.16. In animals with lactic acidosis, the calculated ratio in blood of NAD/NADH was 1437 +/- 230, versus a normal value of 6754 +/- 1250. Both arterial PO2 and blood pressure were normal. Continued infusion of NaHCO3 led to increased blood lactate levels, with cardiorespiratory arrest in 36% of animals. Lactic acidosis did not develop in normal rabbits who were similarly treated. It is concluded that spontaneous lactic acidosis can be produced in diabetic, but not in normal, rabbits by infusion of beta-hydroxybutric acid followed by infusion of NaHCO3.", "contents": "Lactic acidosis: an experimental model. A model of spontaneous lactic acidosis was developed in alloxan diabetic rabbits by infusing intravenously beta-hydroxybutyric acid followed by a continuous infusion of NaHCO3. In half of the animals, the arterial lactate/pyruvate ratio rose from 2.5 mM/0.19mM to 20.4 mM/0.28 mM, and arterial pH fell to 7.16. In animals with lactic acidosis, the calculated ratio in blood of NAD/NADH was 1437 +/- 230, versus a normal value of 6754 +/- 1250. Both arterial PO2 and blood pressure were normal. Continued infusion of NaHCO3 led to increased blood lactate levels, with cardiorespiratory arrest in 36% of animals. Lactic acidosis did not develop in normal rabbits who were similarly treated. It is concluded that spontaneous lactic acidosis can be produced in diabetic, but not in normal, rabbits by infusion of beta-hydroxybutric acid followed by infusion of NaHCO3."}
{"id": "PMID:2839", "title": "[Effect of the nitrogen source in the medium on the activity of glutamine synthetase in Candida tropicalis and on the kinetics of the enzymatic reaction of glutamine synthesis].", "content": "The effect of various nitrogen sources (L-glutamic acid, L-glutamine, L-aspartic acid, L-asparagine, and ammonium sulphate) on the synthetase and transferase activity of glutamine synthetase was studied in Candida tropicalis. These nitrogen sources had different effect on the two activity of the enzyme. Glutamic acid or ammonium sulphate did not produce any considerable action on the kinetic properties of glutamine synthetase of this fodder yeast.", "contents": "[Effect of the nitrogen source in the medium on the activity of glutamine synthetase in Candida tropicalis and on the kinetics of the enzymatic reaction of glutamine synthesis]. The effect of various nitrogen sources (L-glutamic acid, L-glutamine, L-aspartic acid, L-asparagine, and ammonium sulphate) on the synthetase and transferase activity of glutamine synthetase was studied in Candida tropicalis. These nitrogen sources had different effect on the two activity of the enzyme. Glutamic acid or ammonium sulphate did not produce any considerable action on the kinetic properties of glutamine synthetase of this fodder yeast."}
{"id": "PMID:2840", "title": "[Effect of cultivation conditions on cell composition of Pseudomonas methanolica].", "content": "The effect of cultivation conditions on the ocmposition of polymers was studied in the cells of Pseudomonas methanolica, BKM B-1131. The economic coefficient was high and the composition of polymers was normal if the growth was limited by methanol deficiency and the flow rate was low (D = 0.1 hr-1). The composition of the cells did not change but the economic coefficient decreased (0.12--0.21) if the growth was inhibited by pH.", "contents": "[Effect of cultivation conditions on cell composition of Pseudomonas methanolica]. The effect of cultivation conditions on the ocmposition of polymers was studied in the cells of Pseudomonas methanolica, BKM B-1131. The economic coefficient was high and the composition of polymers was normal if the growth was limited by methanol deficiency and the flow rate was low (D = 0.1 hr-1). The composition of the cells did not change but the economic coefficient decreased (0.12--0.21) if the growth was inhibited by pH."}
{"id": "PMID:2841", "title": "[Production of glycolic acid by the cells of Chlorella pyrenoidosa].", "content": "The maximum production of glycolic acid by the cells of Chlorella pyrenoidosa, strain S-39, was found when the cells, grown at the content of carbon dioxide of 2% in the air and illumination of 2000 lx, were transferred to 10(-3) M phosphate buffer (pH 7.0) with barbotage by pure oxygen and illumination of 30,000 lx. The rate of production of glycolic acid during the first five minutes is the same in the light and darkness; later no glycolate is formed in the darkness while in the light glycolate is formed at a lower rate. Bicarbonate inhibits production of glycolate. Negative interaction has been established between oxygen and bicarbonate during their effect on the production of glycolic acid. These data confirm the production of glycolic acid in the cells of Chlorella pyrenoidosa from ribulose diphosphate which is oxidized by molecular oxygen with the participation of ribulose diphosphate carboxylase acting as an oxygenase.", "contents": "[Production of glycolic acid by the cells of Chlorella pyrenoidosa]. The maximum production of glycolic acid by the cells of Chlorella pyrenoidosa, strain S-39, was found when the cells, grown at the content of carbon dioxide of 2% in the air and illumination of 2000 lx, were transferred to 10(-3) M phosphate buffer (pH 7.0) with barbotage by pure oxygen and illumination of 30,000 lx. The rate of production of glycolic acid during the first five minutes is the same in the light and darkness; later no glycolate is formed in the darkness while in the light glycolate is formed at a lower rate. Bicarbonate inhibits production of glycolate. Negative interaction has been established between oxygen and bicarbonate during their effect on the production of glycolic acid. These data confirm the production of glycolic acid in the cells of Chlorella pyrenoidosa from ribulose diphosphate which is oxidized by molecular oxygen with the participation of ribulose diphosphate carboxylase acting as an oxygenase."}
{"id": "PMID:2842", "title": "[Interrelationship between the intestinal microflora of lackey moth, brown-tail moth and the entomopathogenic bacterium Bacillus thuringiensis].", "content": "The interrelationship between the intestine microflora of lackey moth (Malacosoma neustria L.), brown-tail moth (Nygmia phaeorrhoea L.) and entomopathogenic bacteria Bacillus thuringiensis (Berl.), Bac. thuringiensis var. galleriea, and Bac. thuringiensis KR3 was studied in vitro. Various organisms of the intestine microflora of lackey moth display bacteriostatic action towards Bac. thuringiensis var. galleriea and Bac. thuringiensis KR3 which is not typical of the microflora of brown-tail moth that manifests mainly the batericidal action. Yeast cultures have been isolated from the intestines of lackey moth; the cultures stimulated growth of the studied entomopathogenic bacterial test cultures. Therefore, weak virulent action of Bac. thuringiensis towards brown-tail moth, as compared to its action on lackey moth, may be due to the bactericidal properties of some intestine microorganisms of brown-tail moth, and also the absence in their intestines of microorganisms stimulating growth of the entomopathogenic bacteria.", "contents": "[Interrelationship between the intestinal microflora of lackey moth, brown-tail moth and the entomopathogenic bacterium Bacillus thuringiensis]. The interrelationship between the intestine microflora of lackey moth (Malacosoma neustria L.), brown-tail moth (Nygmia phaeorrhoea L.) and entomopathogenic bacteria Bacillus thuringiensis (Berl.), Bac. thuringiensis var. galleriea, and Bac. thuringiensis KR3 was studied in vitro. Various organisms of the intestine microflora of lackey moth display bacteriostatic action towards Bac. thuringiensis var. galleriea and Bac. thuringiensis KR3 which is not typical of the microflora of brown-tail moth that manifests mainly the batericidal action. Yeast cultures have been isolated from the intestines of lackey moth; the cultures stimulated growth of the studied entomopathogenic bacterial test cultures. Therefore, weak virulent action of Bac. thuringiensis towards brown-tail moth, as compared to its action on lackey moth, may be due to the bactericidal properties of some intestine microorganisms of brown-tail moth, and also the absence in their intestines of microorganisms stimulating growth of the entomopathogenic bacteria."}
{"id": "PMID:2843", "title": "[Photoinduced reduction of NAD(P) in the cells of green sulfur bacteria].", "content": "The spectrum of a photoinduced increase in luminescence of the cells of the gree sulphur bacterium Chlorobium limicola f. thiosulfatophilum, within the range of 400 to 520 nm, was found to correspond to the spectrum of luminescence of NADH in the protein-bound form. Photoinduced reduction of NAD(P) in green bacteria, contrary to purple bacteria, is not susceptible to the action of p-chlorocarbonylcyanide phenlhydrazone which uncouples photophosphorylation. Therefore, in Chlorobium limicola f. thiosulfatophilum, NAD(P) is reduced by direct non-cyclic transport of electrons via the photosynthetic chain. NAD(P)H is utilized mainly in the system of CO2 fixation; the process is inhibited by fluoroacetate, and the inhibition is eliminated by substrates of the cycle of carboxylic acids.", "contents": "[Photoinduced reduction of NAD(P) in the cells of green sulfur bacteria]. The spectrum of a photoinduced increase in luminescence of the cells of the gree sulphur bacterium Chlorobium limicola f. thiosulfatophilum, within the range of 400 to 520 nm, was found to correspond to the spectrum of luminescence of NADH in the protein-bound form. Photoinduced reduction of NAD(P) in green bacteria, contrary to purple bacteria, is not susceptible to the action of p-chlorocarbonylcyanide phenlhydrazone which uncouples photophosphorylation. Therefore, in Chlorobium limicola f. thiosulfatophilum, NAD(P) is reduced by direct non-cyclic transport of electrons via the photosynthetic chain. NAD(P)H is utilized mainly in the system of CO2 fixation; the process is inhibited by fluoroacetate, and the inhibition is eliminated by substrates of the cycle of carboxylic acids."}
{"id": "PMID:2844", "title": "[Production of lecithinase by Bacillus thuringiensis].", "content": "The activity of lecithaniase was determined in 24 strains of Bacillus thuringiensis on four growth media. The highest accumulation of lecithinase was found on the Hottinger medium containing 0.5% of glucose and 0.56% of sodium bicarbonate. Lecithinase appears at the logarithmic growth phase, and its activity is maximal after 10 hours of growth (at the beginning of the stationary phase). Biosynthesis and accumulation of lecithinase occur at pH 6.0 to 9.0. Lecithinase was purified by salting out with ammonium sulphate (75% saturation). Lecithinase is a thermolabile protein; it is stable within pH range of 3.0 to 9.0 and is resistant to the action of trypsin and 8M urea.", "contents": "[Production of lecithinase by Bacillus thuringiensis]. The activity of lecithaniase was determined in 24 strains of Bacillus thuringiensis on four growth media. The highest accumulation of lecithinase was found on the Hottinger medium containing 0.5% of glucose and 0.56% of sodium bicarbonate. Lecithinase appears at the logarithmic growth phase, and its activity is maximal after 10 hours of growth (at the beginning of the stationary phase). Biosynthesis and accumulation of lecithinase occur at pH 6.0 to 9.0. Lecithinase was purified by salting out with ammonium sulphate (75% saturation). Lecithinase is a thermolabile protein; it is stable within pH range of 3.0 to 9.0 and is resistant to the action of trypsin and 8M urea."}
{"id": "PMID:2851", "title": "Antibiotic sensitivity pattern of pneumococci relatively insensitive to penicillin and cephalosporin antibiotics.", "content": "Penicillin-insensitive pneumococci, of 10 serotypes, which had been isolated in Australia and New Guinea from healthy carriers and patients with pneumococcal infections, were shown to be relatively resistant to penicillin G, penicillin V, methicillin, cloxacillin, cephaloridine and cephalothin, compared with pneumococci fully sensitive to penicillin G. Most penicillin-insensitive pneumococci either were fully sensitive to ampicillin or showed a slight decrease in sensitivity. The size of inoculum, measured in viable units, had little effect on the minimal inhibitory concentration of penicillin G; this applied to both penicillin-insensitive and penicillin-sensitive pneumococci. In bacterial tests, the minimal bactericidal concentration of penicillin G either equalled or exceeded the minimal inhibitory concentration.", "contents": "Antibiotic sensitivity pattern of pneumococci relatively insensitive to penicillin and cephalosporin antibiotics. Penicillin-insensitive pneumococci, of 10 serotypes, which had been isolated in Australia and New Guinea from healthy carriers and patients with pneumococcal infections, were shown to be relatively resistant to penicillin G, penicillin V, methicillin, cloxacillin, cephaloridine and cephalothin, compared with pneumococci fully sensitive to penicillin G. Most penicillin-insensitive pneumococci either were fully sensitive to ampicillin or showed a slight decrease in sensitivity. The size of inoculum, measured in viable units, had little effect on the minimal inhibitory concentration of penicillin G; this applied to both penicillin-insensitive and penicillin-sensitive pneumococci. In bacterial tests, the minimal bactericidal concentration of penicillin G either equalled or exceeded the minimal inhibitory concentration."}
{"id": "PMID:2856", "title": "Restriction and modification in B. subtilis. Purification and general properties of a restriction endonuclease from strain R.", "content": "All Bacillus subtilis R-type strains showing the phenomena of restriction and modification contain an endonuclease that inactivates in vitro the biological activity of a variety of DNAs lacking R-specific modification, such as transfecting SPPI, SPO2 and phi105 DNA, and transforming B. subtilis 168-type DNA. The corresponding DNAs carrying R-specific modification are resistant to the enzyme. The enzyme has been purified approximately 400-fold and is essentially free from contaminating double strand-directed unspecific exo- or endonuclease activity. Only Mg2+ is required as cofactor. The substrate DNAs are cleaved at specific sites. The double-stranded fragments produced from SPP1 DNA (molecular weight 2.5 x 10(7)) have an average molecular weight of about 3 x 10(5).", "contents": "Restriction and modification in B. subtilis. Purification and general properties of a restriction endonuclease from strain R. All Bacillus subtilis R-type strains showing the phenomena of restriction and modification contain an endonuclease that inactivates in vitro the biological activity of a variety of DNAs lacking R-specific modification, such as transfecting SPPI, SPO2 and phi105 DNA, and transforming B. subtilis 168-type DNA. The corresponding DNAs carrying R-specific modification are resistant to the enzyme. The enzyme has been purified approximately 400-fold and is essentially free from contaminating double strand-directed unspecific exo- or endonuclease activity. Only Mg2+ is required as cofactor. The substrate DNAs are cleaved at specific sites. The double-stranded fragments produced from SPP1 DNA (molecular weight 2.5 x 10(7)) have an average molecular weight of about 3 x 10(5)."}
{"id": "PMID:2857", "title": "Myo-inositol oxygenase from oat seedlings.", "content": "Enzyme preparations from oat seedlings showing the activity of myo-inositol oxygenase (E.C.1.13.99.1) have been described previously. In contrast to myo-inositol oxygenase preparations from other sources, e.g. rat kidney or yeast, the oat enzyme seemed to exhibit a somewhat less stringent activity, acting on other inositols and inositol methyl ethers as well as on myo-inositol. By purification of the enzyme present in the extract from oat seedlings with the help of an affinity gel specific for enzymes acting on myo-inositol a homogeneous enzyme preparation was obtained, which shows the same strict specificity as the myo-inositol oxygenase from other sources. It has a molecular weight of 62,000 and tends to aggregate to oligomers (up to tetramers) under physiological pH-values; in more alkaline media dissociation to monomers is observed. The action on the other inositols and inositol methyl ethers is apparently due to one or more other enzymes, which are also adsorbed on the affinity gel, but can be separated from the myo-inositol oxygenase by elution with increasing concentrations of myo-inositol.", "contents": "Myo-inositol oxygenase from oat seedlings. Enzyme preparations from oat seedlings showing the activity of myo-inositol oxygenase (E.C.1.13.99.1) have been described previously. In contrast to myo-inositol oxygenase preparations from other sources, e.g. rat kidney or yeast, the oat enzyme seemed to exhibit a somewhat less stringent activity, acting on other inositols and inositol methyl ethers as well as on myo-inositol. By purification of the enzyme present in the extract from oat seedlings with the help of an affinity gel specific for enzymes acting on myo-inositol a homogeneous enzyme preparation was obtained, which shows the same strict specificity as the myo-inositol oxygenase from other sources. It has a molecular weight of 62,000 and tends to aggregate to oligomers (up to tetramers) under physiological pH-values; in more alkaline media dissociation to monomers is observed. The action on the other inositols and inositol methyl ethers is apparently due to one or more other enzymes, which are also adsorbed on the affinity gel, but can be separated from the myo-inositol oxygenase by elution with increasing concentrations of myo-inositol."}
{"id": "PMID:2858", "title": "The uptake and extrusion of monovalent cations by isolated heart mitochondria.", "content": "The factors involved in the movement of monovalent cations across the inner membrane of the isolate heart mitochondrion are reviewed. The evidence suggests that the energy-dependent uptake of K+ and Na+ which results in swelling of the matrix is an electrophoretic response to a negative internal potential. There are no clear cut indications that this electrophoretic cation movement is carrier-mediated and possible modes of entry which do not require a carrier are examined. The evidence also suggests that the monovalent cation for proton exchanger (Na+ greater than K+) present in the membrane may participate in the energy-dependent extrusion of accumulated ions. The two processes, electrophoreti c cation uptake (swelling) and exchange-dependent cation extrusion (contraction) may represent a means of controlling the volume of the mitochondrion within the functioning cell. A number of indications point to the possibility that the volume control process may be mediated by the divalent cations Ca+2 and Mg+2. Studies with mercurial reagents also implicate certain membrane thiol groups in the postulated volume control process.", "contents": "The uptake and extrusion of monovalent cations by isolated heart mitochondria. The factors involved in the movement of monovalent cations across the inner membrane of the isolate heart mitochondrion are reviewed. The evidence suggests that the energy-dependent uptake of K+ and Na+ which results in swelling of the matrix is an electrophoretic response to a negative internal potential. There are no clear cut indications that this electrophoretic cation movement is carrier-mediated and possible modes of entry which do not require a carrier are examined. The evidence also suggests that the monovalent cation for proton exchanger (Na+ greater than K+) present in the membrane may participate in the energy-dependent extrusion of accumulated ions. The two processes, electrophoreti c cation uptake (swelling) and exchange-dependent cation extrusion (contraction) may represent a means of controlling the volume of the mitochondrion within the functioning cell. A number of indications point to the possibility that the volume control process may be mediated by the divalent cations Ca+2 and Mg+2. Studies with mercurial reagents also implicate certain membrane thiol groups in the postulated volume control process."}
{"id": "PMID:2859", "title": "[Acid-alkaline equilibrium of the ferri-leg-hemoglobin of the lupine (Lupinus luteus L.) Spectral studies].", "content": "Influence of pH was studied on the absorption spectra (340-670 nm) and on the curves of abnormal dispersion of optic rotation (220-270 nm) of the lupine ferri-leg-hemoglobin (Lb). pH range of the existence of the lupine Lb native form was determined (pH 5.5-11.0 at 20-25degrees C). It has been shown that not only met-hydroxy transition (which is in a complicated manner connected with the ionization of both ligand-bound water and certain amino acid residues of globin) but the ionization of a group with pK approximately 5, too, in the native molecule produces a heterotropic effect onto the haem. Complex analysis of the acidic and alkaline denaturation evidences that these processes are cooperative and proceed via several stages. pK values and the number of tyrosine residues were determined; it has been shown that these amino acid moieties are \"buried\" in the protein molecule. The results are discussed on the basis of a tentative model of the lupine Lb spatial suggested by the authors.", "contents": "[Acid-alkaline equilibrium of the ferri-leg-hemoglobin of the lupine (Lupinus luteus L.) Spectral studies]. Influence of pH was studied on the absorption spectra (340-670 nm) and on the curves of abnormal dispersion of optic rotation (220-270 nm) of the lupine ferri-leg-hemoglobin (Lb). pH range of the existence of the lupine Lb native form was determined (pH 5.5-11.0 at 20-25degrees C). It has been shown that not only met-hydroxy transition (which is in a complicated manner connected with the ionization of both ligand-bound water and certain amino acid residues of globin) but the ionization of a group with pK approximately 5, too, in the native molecule produces a heterotropic effect onto the haem. Complex analysis of the acidic and alkaline denaturation evidences that these processes are cooperative and proceed via several stages. pK values and the number of tyrosine residues were determined; it has been shown that these amino acid moieties are \"buried\" in the protein molecule. The results are discussed on the basis of a tentative model of the lupine Lb spatial suggested by the authors."}
{"id": "PMID:2860", "title": "[Kinetic characteristics of DNA alkylation with some chloroethylmethylarylamines and elimination of alkylated bases from DNA].", "content": "Kinetics of DNA alkylation with 2',3'-o-[N-2-chloroethyl-N-methylamino)benzylidene]uridine (UCHRCL), uridine-5'-methylphosphate (MepUCHRCL) and 4-(N-2-chloroethyl-N-methylamino)benzylamine (NH2CH2RCl) and kinetics of elimination of alkylated bases have been studied. Efficiency of DNA alkylation (p/s-ratio of rate constant of alkylation to the sum of rate constants of by-reactions of an active intermediate formed from the reagent) increases with an increase of the positive charge of the reagents as well as efficiency of tRNA alkylation. Alkylated bases are eliminated from DNA; rate of elimination depends on the structure of the reagent; it decreases in the series NH2CH2R- greater than greater than UCHR-greater than MepUCHR-. Bases alkylated by NH2CH2RCl and UCHRCl are eliminated from DNA during alkylation; therefore plots of DNA alkylation by NH2CH2RCl have a maximum. DNA alkylated by MepUCHRCl is rather stable; alkylated bases are not eliminated during alkylation. Effect of temperature and pH on elimination has been studied.", "contents": "[Kinetic characteristics of DNA alkylation with some chloroethylmethylarylamines and elimination of alkylated bases from DNA]. Kinetics of DNA alkylation with 2',3'-o-[N-2-chloroethyl-N-methylamino)benzylidene]uridine (UCHRCL), uridine-5'-methylphosphate (MepUCHRCL) and 4-(N-2-chloroethyl-N-methylamino)benzylamine (NH2CH2RCl) and kinetics of elimination of alkylated bases have been studied. Efficiency of DNA alkylation (p/s-ratio of rate constant of alkylation to the sum of rate constants of by-reactions of an active intermediate formed from the reagent) increases with an increase of the positive charge of the reagents as well as efficiency of tRNA alkylation. Alkylated bases are eliminated from DNA; rate of elimination depends on the structure of the reagent; it decreases in the series NH2CH2R- greater than greater than UCHR-greater than MepUCHR-. Bases alkylated by NH2CH2RCl and UCHRCl are eliminated from DNA during alkylation; therefore plots of DNA alkylation by NH2CH2RCl have a maximum. DNA alkylated by MepUCHRCl is rather stable; alkylated bases are not eliminated during alkylation. Effect of temperature and pH on elimination has been studied."}
{"id": "PMID:2864", "title": "Immediate hypersensitivity in the guinea pig conjunctiva. II. Effect of treatment with antihistamines, steroids and disodium cromoglycate.", "content": "The effects of antihistamines, steroids and disodium cromoglycate on an immediate hypersensitivity reaction in the guinea pig eye are described in terms of clinical observations, histological examinations of sections of eyes and cytological studies of material from the conjunctival surface. The use of brushes to sample the cells on the conjunctival surface is described. The effect of repeated daily challenges on the reaction is also reported.", "contents": "Immediate hypersensitivity in the guinea pig conjunctiva. II. Effect of treatment with antihistamines, steroids and disodium cromoglycate. The effects of antihistamines, steroids and disodium cromoglycate on an immediate hypersensitivity reaction in the guinea pig eye are described in terms of clinical observations, histological examinations of sections of eyes and cytological studies of material from the conjunctival surface. The use of brushes to sample the cells on the conjunctival surface is described. The effect of repeated daily challenges on the reaction is also reported."}
{"id": "PMID:2865", "title": "[Possibilities and results of shortened hospital treatment in pediatric surgery (author's transl)].", "content": "2582 surgical operations on children - principally abdominal hernias and phimoses - are reported. Inpatient treatment required a stay of 3.2 days, 430 children were treated as outpatients. The 11 pediatricians working in the afflux area unanimously judged the shortened stay in hospital positive. Of the parents interviewed, only 1.3% did not agree with the short hospitalization and 4.8% disagreed with the outpatient therapy. The well-known psychic disturbances of small children by admission to hospital confirmed. The economic importance of a stay which can be reduced by 10 days compared with the present average is pointed out.", "contents": "[Possibilities and results of shortened hospital treatment in pediatric surgery (author's transl)]. 2582 surgical operations on children - principally abdominal hernias and phimoses - are reported. Inpatient treatment required a stay of 3.2 days, 430 children were treated as outpatients. The 11 pediatricians working in the afflux area unanimously judged the shortened stay in hospital positive. Of the parents interviewed, only 1.3% did not agree with the short hospitalization and 4.8% disagreed with the outpatient therapy. The well-known psychic disturbances of small children by admission to hospital confirmed. The economic importance of a stay which can be reduced by 10 days compared with the present average is pointed out."}
{"id": "PMID:2866", "title": "[The diagnostic significance of immunoglobulin determination in chronic liver diseases. II. Relationships between immunoglobulin changes and degree of activity (author's transl)].", "content": "The relationship between the immunograms and aminotransferases, gamma-GT and AP were examined in 715 patients with hepatobiliary diseases closely confirmed by histomorphological criteria and a series of 60 normal subjects. The normal subjects showed positive relationships. These are largely lacking in acute and protracted courses and in chronic aggressive hepatitis. Only relationships of the individual immunoglobulins between themselves can be demonstrated in the aggressive chronic types. Positive relationships are present between immunograms and aminotransferases, gamma-GT and AP in the group with fatty livers, and so are other highly significant positive relationships in toxic hepatitis and toxic cirrhoses of the liver.", "contents": "[The diagnostic significance of immunoglobulin determination in chronic liver diseases. II. Relationships between immunoglobulin changes and degree of activity (author's transl)]. The relationship between the immunograms and aminotransferases, gamma-GT and AP were examined in 715 patients with hepatobiliary diseases closely confirmed by histomorphological criteria and a series of 60 normal subjects. The normal subjects showed positive relationships. These are largely lacking in acute and protracted courses and in chronic aggressive hepatitis. Only relationships of the individual immunoglobulins between themselves can be demonstrated in the aggressive chronic types. Positive relationships are present between immunograms and aminotransferases, gamma-GT and AP in the group with fatty livers, and so are other highly significant positive relationships in toxic hepatitis and toxic cirrhoses of the liver."}
{"id": "PMID:2863", "title": "[pH-dependence of the mechanism of pepsin action].", "content": "N-Acetyl-L-phenylalanine inhibition of the peptic hydrolysis of N-acetyl-L-phenylalanine-L-tyrosine over the pH range 2-4.5 was studied. The mixed character of inhibition which was partially competitive and partially non-competitive allowed us to infer that the separate steps of the enzymatic hydrolysis were pH dependent. The orderliness of the dissociation of the triple enzyme-product-product complex was also pH dependent. The group with pKa approximately 3 influenced the mechanisms of pepsin hydrolysis as strongly as in the case of pepsin catalyzed oxygen isotopic exchange in the acyl amino acid carboxyl group.", "contents": "[pH-dependence of the mechanism of pepsin action]. N-Acetyl-L-phenylalanine inhibition of the peptic hydrolysis of N-acetyl-L-phenylalanine-L-tyrosine over the pH range 2-4.5 was studied. The mixed character of inhibition which was partially competitive and partially non-competitive allowed us to infer that the separate steps of the enzymatic hydrolysis were pH dependent. The orderliness of the dissociation of the triple enzyme-product-product complex was also pH dependent. The group with pKa approximately 3 influenced the mechanisms of pepsin hydrolysis as strongly as in the case of pepsin catalyzed oxygen isotopic exchange in the acyl amino acid carboxyl group."}
{"id": "PMID:2867", "title": "Caffeine enhancement of digestion of DNA by nuclease S1.", "content": "The activity of Aspergillus orzae nuclease S1 on DNA has been investigated under varying pH and metal ion conditions. Nuclease S1 was found to preferentially digest denatured DNA. With native DNA as substrate the enzyme could only digest the DNA when caffeine was added to the reaction mixture. The enzyme was more active in sodium acetate buffer (pH 4.5), than in either standard saline citrate (PH 7.0) or sodium phosphate buffer (pH 6.8). Caffeine was also found to affect the thermal stability of DNA, resulting in a melting profile characterized by two transitions. The first transition (poorly defined) was below the normal melting temperature of the DNA, while the next transition was at the normal melting temperature of the DNA, while the next transition was at the normal melting temperature of the DNA. The susceptibility of caffeine-treated DNA to nuclease digestion seems to be a result of the local unwinding that caffeine causes in the regions of DNA that melt in the first transition. This selective destabilization presumably sensitizes the unwound regions to nuclease hydrolysis. The hydrolysates of the DNA digested by nuclease S1 were subjected first to ion exchange chromatography followed by paper chromatography. The results from this partial characterization of the digestion products showed that they contain mononucleotides as well as oligonucleotides of varying lengths. The base composition of the mononucleotide digests suggests that caffeine has greater preference for interacting with A-T base-pairs in DNA.", "contents": "Caffeine enhancement of digestion of DNA by nuclease S1. The activity of Aspergillus orzae nuclease S1 on DNA has been investigated under varying pH and metal ion conditions. Nuclease S1 was found to preferentially digest denatured DNA. With native DNA as substrate the enzyme could only digest the DNA when caffeine was added to the reaction mixture. The enzyme was more active in sodium acetate buffer (pH 4.5), than in either standard saline citrate (PH 7.0) or sodium phosphate buffer (pH 6.8). Caffeine was also found to affect the thermal stability of DNA, resulting in a melting profile characterized by two transitions. The first transition (poorly defined) was below the normal melting temperature of the DNA, while the next transition was at the normal melting temperature of the DNA, while the next transition was at the normal melting temperature of the DNA. The susceptibility of caffeine-treated DNA to nuclease digestion seems to be a result of the local unwinding that caffeine causes in the regions of DNA that melt in the first transition. This selective destabilization presumably sensitizes the unwound regions to nuclease hydrolysis. The hydrolysates of the DNA digested by nuclease S1 were subjected first to ion exchange chromatography followed by paper chromatography. The results from this partial characterization of the digestion products showed that they contain mononucleotides as well as oligonucleotides of varying lengths. The base composition of the mononucleotide digests suggests that caffeine has greater preference for interacting with A-T base-pairs in DNA."}
{"id": "PMID:2861", "title": "[Isolation and properties of polyphosphatase of Neurospora crassa].", "content": "Polyphosphatase (polyphosphate-phosphohydrolase) has been isolated from mycelium of Neurospora crassa and purified to homogenous state. The enzyme is shown to be strictly specific to high molecular weight inorganic polyphosphates. Km for phosphate in polymeric form is 6.8-10(-4) M. The molecular weight of this enzyme is 50 000 +/- 3000. To display its activity polyphosphatase requires the presence of bivalent cations of some metals, Mg2+ ions being the best activator with Co2+, Mn2+ and Fe2+ ions-slightly less effective.", "contents": "[Isolation and properties of polyphosphatase of Neurospora crassa]. Polyphosphatase (polyphosphate-phosphohydrolase) has been isolated from mycelium of Neurospora crassa and purified to homogenous state. The enzyme is shown to be strictly specific to high molecular weight inorganic polyphosphates. Km for phosphate in polymeric form is 6.8-10(-4) M. The molecular weight of this enzyme is 50 000 +/- 3000. To display its activity polyphosphatase requires the presence of bivalent cations of some metals, Mg2+ ions being the best activator with Co2+, Mn2+ and Fe2+ ions-slightly less effective."}
{"id": "PMID:2862", "title": "[Isolation of rat liver chromatin non-histone protein].", "content": "A chromatin with the protein/DNA ratio of 3.0 was obtained from rat liver cells nuclei. The chromatin was dissolved in 2 M NaCl, pH 7, and reprecipitated by decreasing the ionic strength to 0.4 and increasing pH to 9.0. A fraction of non-histone proteins (NH-1) remained in a supernatant solution, the NH-1/DNA ratio being equal to 1.3 and the ratio of acidic to basic aminoacid residues equal to 1.31. After chromatography on Bio-Rex 70 cation-exchang resin, a fraction (NH-2) with the NH-2/DNA ratio of 1.0 +/- 0.15 and the ratio of acidic to basic aminoacid residues of 1.57 was obtained. According to the data of polyacrylamide gel electrophoresis, the NH-2 fraction contained 2.7% of histone f2 + f3 as an admixture whereas histone f1 was not revealed.", "contents": "[Isolation of rat liver chromatin non-histone protein]. A chromatin with the protein/DNA ratio of 3.0 was obtained from rat liver cells nuclei. The chromatin was dissolved in 2 M NaCl, pH 7, and reprecipitated by decreasing the ionic strength to 0.4 and increasing pH to 9.0. A fraction of non-histone proteins (NH-1) remained in a supernatant solution, the NH-1/DNA ratio being equal to 1.3 and the ratio of acidic to basic aminoacid residues equal to 1.31. After chromatography on Bio-Rex 70 cation-exchang resin, a fraction (NH-2) with the NH-2/DNA ratio of 1.0 +/- 0.15 and the ratio of acidic to basic aminoacid residues of 1.57 was obtained. According to the data of polyacrylamide gel electrophoresis, the NH-2 fraction contained 2.7% of histone f2 + f3 as an admixture whereas histone f1 was not revealed."}
{"id": "PMID:2870", "title": "Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer.", "content": "Nocturnal pain and gastric hypersecretion are common in duodenal ulcer. Therefore, we investigated the antisecretory effects of a new H2-receptor antagonist, cimetidine, in 200-, 300- or 400-mg doses, taken orally at bedtime. The 200-mg dose did not cause a statistically significant change in nocturnal (midnight to 7 a.m.) acid output and had only a borderline effect on pH. However, the 300-mg and 400-mg doses significantly (P less than 0.001) lowered acid output and increased (P less than 0.01) intragastric pH. All doses caused substantial decreases in secretory volume output. After a 400-mg dose, half the patients remained anacidic for eight hours. Dose-related increases of drug blood levels were observed and correlated with the degree and duration of inhibition of acid output. Serum gastrin levels were unaffected. Cimetidine appears to be a potent inhibitor of nocturnal gastric secretion.", "contents": "Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer. Nocturnal pain and gastric hypersecretion are common in duodenal ulcer. Therefore, we investigated the antisecretory effects of a new H2-receptor antagonist, cimetidine, in 200-, 300- or 400-mg doses, taken orally at bedtime. The 200-mg dose did not cause a statistically significant change in nocturnal (midnight to 7 a.m.) acid output and had only a borderline effect on pH. However, the 300-mg and 400-mg doses significantly (P less than 0.001) lowered acid output and increased (P less than 0.01) intragastric pH. All doses caused substantial decreases in secretory volume output. After a 400-mg dose, half the patients remained anacidic for eight hours. Dose-related increases of drug blood levels were observed and correlated with the degree and duration of inhibition of acid output. Serum gastrin levels were unaffected. Cimetidine appears to be a potent inhibitor of nocturnal gastric secretion."}
{"id": "PMID:2872", "title": "[Interaction of yeasts with tannins. II. Study of various yeasts hydrolysing tannic acid in tannin culture media].", "content": "Growth and hydrolytic action on tannins of 6 strains of yeasts (isolated from tanning liquors and xylophagous insects) are studied in culture media containing various concentrations of tannic acid. The influence of medium acidity is also considered. According to the strains, growth is more or less restrained and hydrolytic activity is variable. Except for gallotannins, hydrolysable tannins are not hydrolysed.", "contents": "[Interaction of yeasts with tannins. II. Study of various yeasts hydrolysing tannic acid in tannin culture media]. Growth and hydrolytic action on tannins of 6 strains of yeasts (isolated from tanning liquors and xylophagous insects) are studied in culture media containing various concentrations of tannic acid. The influence of medium acidity is also considered. According to the strains, growth is more or less restrained and hydrolytic activity is variable. Except for gallotannins, hydrolysable tannins are not hydrolysed."}
{"id": "PMID:2873", "title": "Differential inhibition of sclerotial germination in Whetzelinia sclerotiorum.", "content": "A number of diverse compounds including divalent metal ions, simple sugars, and common counterions, buffers, and fungicides were surveyed in the laboratory with regard to ability to inhibit germination of field-collected sclerotia from Whetzelinia sclerotiorum. Many compounds were inhibitory and several were comparable in effectiveness to benomyl and other commercial fungicides. Different levels of a given inhibitor were needed to prevent stipe formation, apothecial formation or mycelial germination. Inhibition was not correlated with ionic strength or related to pH.", "contents": "Differential inhibition of sclerotial germination in Whetzelinia sclerotiorum. A number of diverse compounds including divalent metal ions, simple sugars, and common counterions, buffers, and fungicides were surveyed in the laboratory with regard to ability to inhibit germination of field-collected sclerotia from Whetzelinia sclerotiorum. Many compounds were inhibitory and several were comparable in effectiveness to benomyl and other commercial fungicides. Different levels of a given inhibitor were needed to prevent stipe formation, apothecial formation or mycelial germination. Inhibition was not correlated with ionic strength or related to pH."}
{"id": "PMID:2878", "title": "[Biophysical primary processes in photosynthetic membranes. Data with pulse-spectroscopical methods].", "content": "The electron transfer in the photosynthetic membrane of green plants from H2O to NADP+ is driven by two chlorophyll reaction centers in series. The electron transfer converts one part of the light energy into the form of the reducing power of NADPH. The transfer initiates an electrical field across the membrane. The electrical energy of the charged membrane is an additional state into which light energy is converted. Protolytic reactions coupled with the electron transfer lead to a proton translocation into the inner space of the thylakoid. The discharging of the ectrically energized membrane by H+ efflux is coupled with the formation of ATP.", "contents": "[Biophysical primary processes in photosynthetic membranes. Data with pulse-spectroscopical methods]. The electron transfer in the photosynthetic membrane of green plants from H2O to NADP+ is driven by two chlorophyll reaction centers in series. The electron transfer converts one part of the light energy into the form of the reducing power of NADPH. The transfer initiates an electrical field across the membrane. The electrical energy of the charged membrane is an additional state into which light energy is converted. Protolytic reactions coupled with the electron transfer lead to a proton translocation into the inner space of the thylakoid. The discharging of the ectrically energized membrane by H+ efflux is coupled with the formation of ATP."}
{"id": "PMID:2891", "title": "Mechanism of action of anticonvulsants. Role of the differential effects on the active uptake of putative neurotransmitters.", "content": "The effect of pentobarbital and phenytoin on the high-affinity uptake of the putative neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and norepinephrine was examined in synaptosomes prepared from rat brain. Both pentobarbital and phenytoin inhibited the uptake of norepinephrine. Pentobarbital increased the uptake of GABA twofold and only slightly increased the uptake of glutamate. Phenytoin facilitated GABA uptake to a lesser extent than did pentobarbital, but also increased the uptake of glutamate. This suggests that these drugs may limit the propagation of seizures through the balance of excitatory glutamate pathways and inhibitory GABA and norepinephrine pathways. The contrasting effects of these drugs on GABA and glutamate uptake may be related to the hypnotic properties of pentobarbital not present in phenytoin.", "contents": "Mechanism of action of anticonvulsants. Role of the differential effects on the active uptake of putative neurotransmitters. The effect of pentobarbital and phenytoin on the high-affinity uptake of the putative neurotransmitters gamma-aminobutyric acid (GABA), glutamate, and norepinephrine was examined in synaptosomes prepared from rat brain. Both pentobarbital and phenytoin inhibited the uptake of norepinephrine. Pentobarbital increased the uptake of GABA twofold and only slightly increased the uptake of glutamate. Phenytoin facilitated GABA uptake to a lesser extent than did pentobarbital, but also increased the uptake of glutamate. This suggests that these drugs may limit the propagation of seizures through the balance of excitatory glutamate pathways and inhibitory GABA and norepinephrine pathways. The contrasting effects of these drugs on GABA and glutamate uptake may be related to the hypnotic properties of pentobarbital not present in phenytoin."}
{"id": "PMID:2892", "title": "Studies of maternal plasma prolactin and amniotic fluid prolactin. Effects of chlorpromazine and prostaglandin F2alpha.", "content": "We have studied the effect of chlorpromazine and PGF2alpha on the blood and amniotic fluid levels of prolactin over a 1-hour period of time in women who were in the 14th-20th week of gestation. Following intramuscular injection of chlorpromazine, maternal plasma prolactin rose 1.0- to 2.5-fold. No significant change was noted in maternal plasma after PGF2alpha administration. Amniotic fluid prolactin declined by 6 to 56%. These changes may be dilutional.", "contents": "Studies of maternal plasma prolactin and amniotic fluid prolactin. Effects of chlorpromazine and prostaglandin F2alpha. We have studied the effect of chlorpromazine and PGF2alpha on the blood and amniotic fluid levels of prolactin over a 1-hour period of time in women who were in the 14th-20th week of gestation. Following intramuscular injection of chlorpromazine, maternal plasma prolactin rose 1.0- to 2.5-fold. No significant change was noted in maternal plasma after PGF2alpha administration. Amniotic fluid prolactin declined by 6 to 56%. These changes may be dilutional."}
{"id": "PMID:2895", "title": "[Gonadotropin induced steriodogenesis in prepubertal boys (author's transl)].", "content": "We examined the capacity of reaction in the endocrine tissue of testes in prepubertal boys. 18 boys were endocrinologically healthy, six suffered from cryptorchidism on one or both sides. After a single dose of HCG (5000 IU/m) we found an increase of pregnantriol excretion in the 24 h urine in all subjects studied except in the case of surgically proved anorchia. In all except one boy we found a sharp increase in testosterone after HCG administration.", "contents": "[Gonadotropin induced steriodogenesis in prepubertal boys (author's transl)]. We examined the capacity of reaction in the endocrine tissue of testes in prepubertal boys. 18 boys were endocrinologically healthy, six suffered from cryptorchidism on one or both sides. After a single dose of HCG (5000 IU/m) we found an increase of pregnantriol excretion in the 24 h urine in all subjects studied except in the case of surgically proved anorchia. In all except one boy we found a sharp increase in testosterone after HCG administration."}
{"id": "PMID:2896", "title": "Cobalamins in fibroblasts cultured from normal control subjects and patients with methylmalonic aciduria.", "content": "The intracellular content and proportional distribution of B12 (cobalamin) derivatives in fibroblasts cultured from patients with various forms of methylmalonic aciduria, as well as from normal control subjects, has been determined by a two-dimensional chromatobioautographic technique. Each line of fibroblasts was grown in the presence of four concentrations of cobalamin, ranging from the 0.04-0.07 pmol/ml contained in the basal medium to 74 pmol/ml (100 ng/ml), added in form of hydroxocobalamin (OH-CHl). Control cells grown in the basal medium contained substantial proportions of both methylcobalamin (MeCbl) and adenysylcobalamin (AdoCbl), with the former predominating. As increasing concentrations of OH-CBl were added to the growth medium, the total cellular cobalamin content increased without marked changes in the relative proportions of MeCbl, AdoCbl, and OH-Cbl. Three different patterns were discernable in the cobalamin distributions of the cells cultured from patients with methylmalonic aciduria (Table 1 and Fig. 1).", "contents": "Cobalamins in fibroblasts cultured from normal control subjects and patients with methylmalonic aciduria. The intracellular content and proportional distribution of B12 (cobalamin) derivatives in fibroblasts cultured from patients with various forms of methylmalonic aciduria, as well as from normal control subjects, has been determined by a two-dimensional chromatobioautographic technique. Each line of fibroblasts was grown in the presence of four concentrations of cobalamin, ranging from the 0.04-0.07 pmol/ml contained in the basal medium to 74 pmol/ml (100 ng/ml), added in form of hydroxocobalamin (OH-CHl). Control cells grown in the basal medium contained substantial proportions of both methylcobalamin (MeCbl) and adenysylcobalamin (AdoCbl), with the former predominating. As increasing concentrations of OH-CBl were added to the growth medium, the total cellular cobalamin content increased without marked changes in the relative proportions of MeCbl, AdoCbl, and OH-Cbl. Three different patterns were discernable in the cobalamin distributions of the cells cultured from patients with methylmalonic aciduria (Table 1 and Fig. 1)."}
{"id": "PMID:2897", "title": "Intrauterine torsion of an intra-abdominal testis.", "content": "Intra-abdominal torsion of an undescended testis is a rare surgical problem in the neonate. However, one must consider the possibility of intrauterine torsion in a neonate who presents with an undescended testis and an abdominal mass.", "contents": "Intrauterine torsion of an intra-abdominal testis. Intra-abdominal torsion of an undescended testis is a rare surgical problem in the neonate. However, one must consider the possibility of intrauterine torsion in a neonate who presents with an undescended testis and an abdominal mass."}
{"id": "PMID:2898", "title": "Issues in treatment efficacy research with alcoholics.", "content": "A variety of therapeutic strategies have been used in the treatment of alcoholic patients. Within this context, behavioral techniques have been widely employed with varying degree of effectiveness. This paper attempts to explore theoretically 2 widely used behavioral therapeutic methods, systematic desensitization and covert sensitization, along with traditional insight-oriented therapy. Possible merits and limitations of applying these treatment approaches to alcoholic patients are explored.", "contents": "Issues in treatment efficacy research with alcoholics. A variety of therapeutic strategies have been used in the treatment of alcoholic patients. Within this context, behavioral techniques have been widely employed with varying degree of effectiveness. This paper attempts to explore theoretically 2 widely used behavioral therapeutic methods, systematic desensitization and covert sensitization, along with traditional insight-oriented therapy. Possible merits and limitations of applying these treatment approaches to alcoholic patients are explored."}
{"id": "PMID:2899", "title": "Semantic desensitization: language conditioning or demand characteristics manipulation?", "content": "Previous studies in language conditioning, especially those called semantic desensitization, have shown changes in self-report, behavioral measures, and the semantic meaning of the target concept following treatment. This last has been proposed as a causal variable but experimental and control groups differed greatly in terms of their demand characteristics. The present study included a placebo group with demand characteristics similar to those of the control group. The target area was self-concept (18 male Ss, 9 female Ss). Significant changes in self-report and actual performance with a hand dynamometer were obtained but these were as great for the placebo group as for the experimental groups. It was suggested that factors other than conditioning are of importance in semantic desensitization.", "contents": "Semantic desensitization: language conditioning or demand characteristics manipulation? Previous studies in language conditioning, especially those called semantic desensitization, have shown changes in self-report, behavioral measures, and the semantic meaning of the target concept following treatment. This last has been proposed as a causal variable but experimental and control groups differed greatly in terms of their demand characteristics. The present study included a placebo group with demand characteristics similar to those of the control group. The target area was self-concept (18 male Ss, 9 female Ss). Significant changes in self-report and actual performance with a hand dynamometer were obtained but these were as great for the placebo group as for the experimental groups. It was suggested that factors other than conditioning are of importance in semantic desensitization."}
{"id": "PMID:2901", "title": "[Polyarteritis nodosa: general aspects and occurrence in domestic animals, particularly in association with nosematosis in blue foxex (author's transl)].", "content": "A survey of polyarteritis nodosa in domestic animals is presented, including a description of the patho-morphological lesions and a discussion on the causal factors. This vascular disease occurs in domestic animals in association with both viral infections (infectious plasmacytosis in mink), bacterial infections (erysipelas in swine), and protozoan infections (nosematosis in blue foxes). The conclusion is drawn that the observations in domestic animals support the view that immunological disturbances are involved as pathogenetic mechanisms. Nosematosis is dealt with in more detail; the infecting agent (fig. 1), Nosema cuniculi (Encephalitozoon cuniculi), is a widespread mamalian parasite, which causes cerebral and renal lesions in blue foxes of the same type as in animals of other species. In addition, the vascular system throughout the body is affected, resulting in patho-morphological alterations corresponding to classical polyarteritis nodosa (Fig. 2). In the early stages of involvement, masses of parasitic organisms are regularly found within the walls of affected arteries (Fig. 3). This disease is frequently lethal, and always accompanied by elevated values of gamma globulins. Both the hypergammaglobulinemia and the tissue lesions, seem at times, at least in part, to be reversible.", "contents": "[Polyarteritis nodosa: general aspects and occurrence in domestic animals, particularly in association with nosematosis in blue foxex (author's transl)]. A survey of polyarteritis nodosa in domestic animals is presented, including a description of the patho-morphological lesions and a discussion on the causal factors. This vascular disease occurs in domestic animals in association with both viral infections (infectious plasmacytosis in mink), bacterial infections (erysipelas in swine), and protozoan infections (nosematosis in blue foxes). The conclusion is drawn that the observations in domestic animals support the view that immunological disturbances are involved as pathogenetic mechanisms. Nosematosis is dealt with in more detail; the infecting agent (fig. 1), Nosema cuniculi (Encephalitozoon cuniculi), is a widespread mamalian parasite, which causes cerebral and renal lesions in blue foxes of the same type as in animals of other species. In addition, the vascular system throughout the body is affected, resulting in patho-morphological alterations corresponding to classical polyarteritis nodosa (Fig. 2). In the early stages of involvement, masses of parasitic organisms are regularly found within the walls of affected arteries (Fig. 3). This disease is frequently lethal, and always accompanied by elevated values of gamma globulins. Both the hypergammaglobulinemia and the tissue lesions, seem at times, at least in part, to be reversible."}
{"id": "PMID:2902", "title": "[Caesarean section in sows anesthetized with Azaperone and Metomidate (author's transl)].", "content": "213 caesarean sections and 157 hysterectomies were carried out in gilts and sows with different body weight (table I). The neuroleptic Azaperone and the hypnotic Metomidate were used for anaesthesia with different administration (table II). Local analgesia and premedication with Atropine. The duration of the anaesthesia was 45 minutes and where prolongation was necessary, Metomidate, Azaperone or barbiturates were used alone or in combinations once or more. The indications (table III) for caesarean section were retarded birth in 70 sows, dislocation of uterus in 74 sows and in 69 sows by other indications. Hysterectomy was indicated by retarded birth in 93 sows, dislocations of uterus in 40 cases and in 24 cases by other indications. In 183 operations (table IV) 1006 living piglets were delivered, and 703 were alive at discharge (70%). The chances of survival depends on the composition of the litter, in litters of piglets alive only, 76% survived at discharge; in litters consisting of both alive and stillborn 69% survived and 59% survived in litters consisting of piglets alive and post mortem piglets. The total survival of the sows was 78%, 80% after caesarean section and 76% after hysterectomy. It is pointed out that most of the patients operated were in a very late phase of birth.", "contents": "[Caesarean section in sows anesthetized with Azaperone and Metomidate (author's transl)]. 213 caesarean sections and 157 hysterectomies were carried out in gilts and sows with different body weight (table I). The neuroleptic Azaperone and the hypnotic Metomidate were used for anaesthesia with different administration (table II). Local analgesia and premedication with Atropine. The duration of the anaesthesia was 45 minutes and where prolongation was necessary, Metomidate, Azaperone or barbiturates were used alone or in combinations once or more. The indications (table III) for caesarean section were retarded birth in 70 sows, dislocation of uterus in 74 sows and in 69 sows by other indications. Hysterectomy was indicated by retarded birth in 93 sows, dislocations of uterus in 40 cases and in 24 cases by other indications. In 183 operations (table IV) 1006 living piglets were delivered, and 703 were alive at discharge (70%). The chances of survival depends on the composition of the litter, in litters of piglets alive only, 76% survived at discharge; in litters consisting of both alive and stillborn 69% survived and 59% survived in litters consisting of piglets alive and post mortem piglets. The total survival of the sows was 78%, 80% after caesarean section and 76% after hysterectomy. It is pointed out that most of the patients operated were in a very late phase of birth."}
{"id": "PMID:2905", "title": "Formation and in-vivo-distribution of different 99mTc-Sn-pyrophosphate complexes.", "content": "The formation of two different 99mTc-Sn-pyrophosphate complexes was determined by evaluation of their in vivo distribution in rats. It was found that formation of a 2 : 2 Sn : PyP complex, which is bone seeking, is depending as well on the pyrophosphate as on the hydrogen ion concentration in the equilibrium. On the contrary, formation of a 2 : 1 Sn : PyP complex, which shows no bone affinity but concentrate in the kidneys, is hydrogen ion independent and occurs even at very low pyrophosphate concentrations. The probable structure of these complexes is discussed.", "contents": "Formation and in-vivo-distribution of different 99mTc-Sn-pyrophosphate complexes. The formation of two different 99mTc-Sn-pyrophosphate complexes was determined by evaluation of their in vivo distribution in rats. It was found that formation of a 2 : 2 Sn : PyP complex, which is bone seeking, is depending as well on the pyrophosphate as on the hydrogen ion concentration in the equilibrium. On the contrary, formation of a 2 : 1 Sn : PyP complex, which shows no bone affinity but concentrate in the kidneys, is hydrogen ion independent and occurs even at very low pyrophosphate concentrations. The probable structure of these complexes is discussed."}
{"id": "PMID:2911", "title": "Separation of (3') deoxynucleotides with cation exchange columns.", "content": "A procedure is described for a one-step separation of synthetic (3') deoxynucleotides purchased commercially or those purified and isolated from the enzymatic digests of DNA. The method is simple. A 50 ml buret was used for column which was filled with the resin slurry and packed at water aspirator pressure. The compounds were eluted from the column at atmospheric pressure under gravity flow using a fraction collector and read on a Beckman DU spectrophotometer. Recoveries were in excess of 90% and no accessory devices were required. The use of a volatile buffer, e.g. ammonium formate facilitated the recovery of the purified material by allowing the evaporation of the medium in which the sample was eluted.", "contents": "Separation of (3') deoxynucleotides with cation exchange columns. A procedure is described for a one-step separation of synthetic (3') deoxynucleotides purchased commercially or those purified and isolated from the enzymatic digests of DNA. The method is simple. A 50 ml buret was used for column which was filled with the resin slurry and packed at water aspirator pressure. The compounds were eluted from the column at atmospheric pressure under gravity flow using a fraction collector and read on a Beckman DU spectrophotometer. Recoveries were in excess of 90% and no accessory devices were required. The use of a volatile buffer, e.g. ammonium formate facilitated the recovery of the purified material by allowing the evaporation of the medium in which the sample was eluted."}
{"id": "PMID:2912", "title": "Interactions between anticonvulsants.", "content": "Anticonvulsant drug interactions have been investigated using multiple linear regression analyses. The one statistically significant interaction found was that in which phenytoin dosage decreased plasma carbamazepine concentrations. There was a suggestion that carbamazepine and phenobarb dosage tended to increase phenytoin levels. No interaction was detected between phenytoin and sulthiame. Studies in individuals suggested that ethosuximide may increase plasma phenytoin concentration and that clonazepam tends to decrease carbamazepine and phenytoin concentrations.", "contents": "Interactions between anticonvulsants. Anticonvulsant drug interactions have been investigated using multiple linear regression analyses. The one statistically significant interaction found was that in which phenytoin dosage decreased plasma carbamazepine concentrations. There was a suggestion that carbamazepine and phenobarb dosage tended to increase phenytoin levels. No interaction was detected between phenytoin and sulthiame. Studies in individuals suggested that ethosuximide may increase plasma phenytoin concentration and that clonazepam tends to decrease carbamazepine and phenytoin concentrations."}
{"id": "PMID:2926", "title": "Renin and hemodynamic changes via central adrenergic, cholinergic, and sodium receptor mechanisms in conscious rats.", "content": "The effects of centrally administered autonomic drugs and hypertonic saline on renin release were studied in the conscious rat. A 0.3 mug intraventricular dose of isoproterenol, which is one-thirtieth of the intraperitoneal dose required to stimulate renin release, induced the release of renin into the systemic circulation. Norepinephrine had no effect on renin release in the same dose range. Hypertonic saline and carbachol suppressed renin release. Alterations in renin release were preceded by a reciprocal change in blood pressure. These results suggest a central nervous system site for sodium, beta-adrenergic, and cholinergic receptors in altering renin release and blood pressure.", "contents": "Renin and hemodynamic changes via central adrenergic, cholinergic, and sodium receptor mechanisms in conscious rats. The effects of centrally administered autonomic drugs and hypertonic saline on renin release were studied in the conscious rat. A 0.3 mug intraventricular dose of isoproterenol, which is one-thirtieth of the intraperitoneal dose required to stimulate renin release, induced the release of renin into the systemic circulation. Norepinephrine had no effect on renin release in the same dose range. Hypertonic saline and carbachol suppressed renin release. Alterations in renin release were preceded by a reciprocal change in blood pressure. These results suggest a central nervous system site for sodium, beta-adrenergic, and cholinergic receptors in altering renin release and blood pressure."}
{"id": "PMID:2927", "title": "Hepatic sodium-potassium exchange induced by adrenomimetic amines.", "content": "The effects of catecholamines on hepatic K+ and Na+ movements were studied in anesthetized dogs by measuring systemic arterial and hepatic venous electrolyte composition following intraportal injections of adrenergic agonists. All catecholamines studied caused the initial loss and subsequent uptake of K+ by the liver. The loss of hepatic K+ was accompanied by an uptake of Na+ at a 1:1 ratio. This accumulation of Na+ continued, although at a slower rate, for at least 8 min. Epinephrine and norepinephrine were much more potent in these effects than either phenylephrine or isoproterenol. Neither alpha- nor beta-adrenergic blockade, singly or in combination, had an appreciable effect on the magnitude or duration of the observed ion shifts. It is concluded that the predominant effect of catecholamines is to produce a net accumulation of hepatic Na+, and that the mechanism governing hepatic ion movements is nonadrenergic as defined by stimulation by specific adrenergic agonists and inhibition by specific adrenergic antagonists.", "contents": "Hepatic sodium-potassium exchange induced by adrenomimetic amines. The effects of catecholamines on hepatic K+ and Na+ movements were studied in anesthetized dogs by measuring systemic arterial and hepatic venous electrolyte composition following intraportal injections of adrenergic agonists. All catecholamines studied caused the initial loss and subsequent uptake of K+ by the liver. The loss of hepatic K+ was accompanied by an uptake of Na+ at a 1:1 ratio. This accumulation of Na+ continued, although at a slower rate, for at least 8 min. Epinephrine and norepinephrine were much more potent in these effects than either phenylephrine or isoproterenol. Neither alpha- nor beta-adrenergic blockade, singly or in combination, had an appreciable effect on the magnitude or duration of the observed ion shifts. It is concluded that the predominant effect of catecholamines is to produce a net accumulation of hepatic Na+, and that the mechanism governing hepatic ion movements is nonadrenergic as defined by stimulation by specific adrenergic agonists and inhibition by specific adrenergic antagonists."}
{"id": "PMID:2928", "title": "Canine cardiac lymph potassium, pH and flow after experimental myocardial infarction.", "content": "Canine cardiac lymph was studied after acute experimental myocardial infarction. The lymph potassium concentration remained the same, the lymph potassium content increased, the lymph pH decreased, and the lymph flow increased while the serum potassium and pH remained the same. It is suggested that localized hypoxia may result in cellular changes that release substances, e.g., potassium, to the interstitial space where they mobilize fluid and enhance lymph flow.", "contents": "Canine cardiac lymph potassium, pH and flow after experimental myocardial infarction. Canine cardiac lymph was studied after acute experimental myocardial infarction. The lymph potassium concentration remained the same, the lymph potassium content increased, the lymph pH decreased, and the lymph flow increased while the serum potassium and pH remained the same. It is suggested that localized hypoxia may result in cellular changes that release substances, e.g., potassium, to the interstitial space where they mobilize fluid and enhance lymph flow."}
{"id": "PMID:2929", "title": "Regulation of proinsulin synthesis in isolated rat islets.", "content": "(1) A system is described for studying the short-term effects of agents on proinsulin synthesis in vitro, as measured by the incorporation of [3H]leucine into isolated proinsulin. (2) Of the agents tested, glucose has the most marked, and apparently earliest, effect on proinsulin synthesis. (3) The adenyl cyclase system participates in the regulation of proinsulin synthesis since exogenous cyclic AMP, glucagon, and caffeine are stimulatory. When cyclic AMP is added to the medium in the presence of glucose, it is the most potent agent acting on the adenyl cyclase-phosphodiesterase system. (4) The addition of NADPH to isolated rat islets inhibits proinsulin and Bulk Protein synthesis in vitro.", "contents": "Regulation of proinsulin synthesis in isolated rat islets. (1) A system is described for studying the short-term effects of agents on proinsulin synthesis in vitro, as measured by the incorporation of [3H]leucine into isolated proinsulin. (2) Of the agents tested, glucose has the most marked, and apparently earliest, effect on proinsulin synthesis. (3) The adenyl cyclase system participates in the regulation of proinsulin synthesis since exogenous cyclic AMP, glucagon, and caffeine are stimulatory. When cyclic AMP is added to the medium in the presence of glucose, it is the most potent agent acting on the adenyl cyclase-phosphodiesterase system. (4) The addition of NADPH to isolated rat islets inhibits proinsulin and Bulk Protein synthesis in vitro."}
{"id": "PMID:2930", "title": "Myocardial substrate utilization in anaphylactic shock.", "content": "Changes in myocardial substrate utilization were studied in anesthetized dogs following the production of anaphylactic shock. Mean arterial blood pressure, cardiac output, and pH decreased significantly during this form of shock. Myocardial FFA oxidation was greatly diminished especially within the first hour following challenge and lactate uptake more than doubled during the same time. Thus, it is concluded that myocardial substrate utilization shifted away from FFA and towards lactate during anaphylactic shock and these changes resembled those observed following an acute, severe hemorrhage, or the administration of E. coli endotoxin.", "contents": "Myocardial substrate utilization in anaphylactic shock. Changes in myocardial substrate utilization were studied in anesthetized dogs following the production of anaphylactic shock. Mean arterial blood pressure, cardiac output, and pH decreased significantly during this form of shock. Myocardial FFA oxidation was greatly diminished especially within the first hour following challenge and lactate uptake more than doubled during the same time. Thus, it is concluded that myocardial substrate utilization shifted away from FFA and towards lactate during anaphylactic shock and these changes resembled those observed following an acute, severe hemorrhage, or the administration of E. coli endotoxin."}
{"id": "PMID:2931", "title": "The influence of drug-induced alterations in the pressor-inotropic state on left ventricular dynamics.", "content": "These experiments present new data, obtained by direct measurement, describing the influence of Phe, NE, and ISO on ventricular MF or load. Measurement of MF along with measurements of ventricular pressure, size, and inotropic state allows for a more complete and meaningful characterization of the response of the intact ventricle to pharmacological interventions.", "contents": "The influence of drug-induced alterations in the pressor-inotropic state on left ventricular dynamics. These experiments present new data, obtained by direct measurement, describing the influence of Phe, NE, and ISO on ventricular MF or load. Measurement of MF along with measurements of ventricular pressure, size, and inotropic state allows for a more complete and meaningful characterization of the response of the intact ventricle to pharmacological interventions."}
{"id": "PMID:2932", "title": "The effects of salicylic acid on metabolism and potassium ion content in yeast.", "content": "Under anaerobic conditions, at low pH and 30 degrees, commercial baker's yeast loses K+ ion in the presence of salicylic acid. Glucose utilization is inhibited. In suspensions containing no glucose, carbohydrate stores of the cell are dissimilated to carbon dioxide and alcohol. The ion loss and inhibitory effects of salicylic acid on glucose utilization are reversed by washing the cells free of salicylate. The loss of K+ appears to be due at least partly to a K+-H+ exchange process. An unexplained maximum is seen in the curves of either net K+ loss or K+ efflux versus salicylic acid concentration. At 6 degrees the effects of salicylic acid on both endogenous metabolism and net K+ loss are minimal. Furthermore, no maximum is seen in the K+ loss-salicyclic concentration curve at this temperature. It is generalized that salicylic acid or salicylate may elicit K+ leakage from many types of cells, i.e., a fundamental action of this compound may be its ability to affect (reduce) K+ content of the cell; furthermore, it appears that the salicylate effects on K+ loss may be associated in an as-yet-unknown manner with the metabolic effects of this compound. The effects of salicylate on K+ loss in yeast may not be unique for this compound, since no experiments of this nature have been done with other penetrating undissociated acids.", "contents": "The effects of salicylic acid on metabolism and potassium ion content in yeast. Under anaerobic conditions, at low pH and 30 degrees, commercial baker's yeast loses K+ ion in the presence of salicylic acid. Glucose utilization is inhibited. In suspensions containing no glucose, carbohydrate stores of the cell are dissimilated to carbon dioxide and alcohol. The ion loss and inhibitory effects of salicylic acid on glucose utilization are reversed by washing the cells free of salicylate. The loss of K+ appears to be due at least partly to a K+-H+ exchange process. An unexplained maximum is seen in the curves of either net K+ loss or K+ efflux versus salicylic acid concentration. At 6 degrees the effects of salicylic acid on both endogenous metabolism and net K+ loss are minimal. Furthermore, no maximum is seen in the K+ loss-salicyclic concentration curve at this temperature. It is generalized that salicylic acid or salicylate may elicit K+ leakage from many types of cells, i.e., a fundamental action of this compound may be its ability to affect (reduce) K+ content of the cell; furthermore, it appears that the salicylate effects on K+ loss may be associated in an as-yet-unknown manner with the metabolic effects of this compound. The effects of salicylate on K+ loss in yeast may not be unique for this compound, since no experiments of this nature have been done with other penetrating undissociated acids."}
{"id": "PMID:2933", "title": "The size pH, and redox potential of the cecum in mice associated with various microbial floras.", "content": "Cecal size and in situ redox potential and pH of cecal contents were determined in conventionally reared mice and mice reared under a variety of gnotobiotic conditions: germfree, monoassociated with a cecal Clostridium sp., hexaflora-associated and thermoduric polyflora-associated. The mean Eh was approximately +200 mV in germfree and -200 mV in conventional mice. The Eh was close to zero in the monoassociated mice, thus occupying a position intermediate between the germfree and conventional mice. The potentials observed in the hexaflora and the thermoduric flora groups were indistinguishable from those of conventional animals. The degree of normalization was more advanced with respect to the redox potential than to the cecal size in the various gnotobiotic groups. In the thermoduric polyflora-associated group, normalization was observed in both cecal size and redox potential. This demonstrates that normalization can be accomplished with a relatively simplified microflora, at least with regard to the parameters studied.", "contents": "The size pH, and redox potential of the cecum in mice associated with various microbial floras. Cecal size and in situ redox potential and pH of cecal contents were determined in conventionally reared mice and mice reared under a variety of gnotobiotic conditions: germfree, monoassociated with a cecal Clostridium sp., hexaflora-associated and thermoduric polyflora-associated. The mean Eh was approximately +200 mV in germfree and -200 mV in conventional mice. The Eh was close to zero in the monoassociated mice, thus occupying a position intermediate between the germfree and conventional mice. The potentials observed in the hexaflora and the thermoduric flora groups were indistinguishable from those of conventional animals. The degree of normalization was more advanced with respect to the redox potential than to the cecal size in the various gnotobiotic groups. In the thermoduric polyflora-associated group, normalization was observed in both cecal size and redox potential. This demonstrates that normalization can be accomplished with a relatively simplified microflora, at least with regard to the parameters studied."}
{"id": "PMID:2934", "title": "Plasma prolactin levels in maturing intact and cryptorchid male rats: development of stress response.", "content": "In order to determine the possible role of the seminiferous tubules in the regulation of prolactin secretion during sexual development, male rats were rendered cryptorchid at 22 days of age, and thereafter different groups of animals were decapitated at 8-10 day intervals between Day 32 and Day 70. Cryptorchid rats showed destruction of the germinal epithelium accompanied by increased plasma FSH and, to a much lesser extent, increased plasma LH titers. Nevertheless, plasma prolactin levels were similar to those of intact controls throughout the entire period studied. Plasma prolactin titers in intact controls remained uniformly low from Day 20 to Day 70, contrasting with previous reports in which increasing prolactin levels have been observed during sexual development. To determine the reason for this apparent discrepancy, a longitudinal experiment was conducted in which intact and cryptorchid male rats were bled every 10 days from Day 30 to Day 70, following a 3-min period of exposure to ether fumes. The prolactin response to this stress increased markedly with age. A similar pattern of prolactin was observed in a cross-sectional study in which different groups of intact animals were bled following a 3-min period of ether exposure, at ages ranging from 20 to 70 daysmthe results indicate that unlike FSH secretion, prolactin secretion is not controlled by the seminiferous tubules. In addition, they suggest that the pattern of increasing plasma prolactin previously described in the developing male rat is at least in part caused by an age-dependent increase in responsiveness of prolactin to stress.", "contents": "Plasma prolactin levels in maturing intact and cryptorchid male rats: development of stress response. In order to determine the possible role of the seminiferous tubules in the regulation of prolactin secretion during sexual development, male rats were rendered cryptorchid at 22 days of age, and thereafter different groups of animals were decapitated at 8-10 day intervals between Day 32 and Day 70. Cryptorchid rats showed destruction of the germinal epithelium accompanied by increased plasma FSH and, to a much lesser extent, increased plasma LH titers. Nevertheless, plasma prolactin levels were similar to those of intact controls throughout the entire period studied. Plasma prolactin titers in intact controls remained uniformly low from Day 20 to Day 70, contrasting with previous reports in which increasing prolactin levels have been observed during sexual development. To determine the reason for this apparent discrepancy, a longitudinal experiment was conducted in which intact and cryptorchid male rats were bled every 10 days from Day 30 to Day 70, following a 3-min period of exposure to ether fumes. The prolactin response to this stress increased markedly with age. A similar pattern of prolactin was observed in a cross-sectional study in which different groups of intact animals were bled following a 3-min period of ether exposure, at ages ranging from 20 to 70 daysmthe results indicate that unlike FSH secretion, prolactin secretion is not controlled by the seminiferous tubules. In addition, they suggest that the pattern of increasing plasma prolactin previously described in the developing male rat is at least in part caused by an age-dependent increase in responsiveness of prolactin to stress."}
{"id": "PMID:2935", "title": "Synthesis of 5-substituted isophthalic acids and competitive inhibition studies with bovine liver glutamate dehydrogenase.", "content": "Isophthalic acid, 5-carboxy-, 5-hydroxy-, 5-methoxy-, 5-fluoro-, 5-bromo-, 5-cyano-, and 5-methylisophthalic acid were inhibitors competitive with L-glutamate for bovine liver glutamate dehydrogenase. The extent of inhibition by the derived compounds was not much greater than that obtained with the parent compound, isophthalic acid. A plot of pKi versus pH showed the presence of an ionizable group (pKa 7.4-7.8) at the enzyme active site which interacted with the substitutent at the 5 position of the substituted isophthalates.", "contents": "Synthesis of 5-substituted isophthalic acids and competitive inhibition studies with bovine liver glutamate dehydrogenase. Isophthalic acid, 5-carboxy-, 5-hydroxy-, 5-methoxy-, 5-fluoro-, 5-bromo-, 5-cyano-, and 5-methylisophthalic acid were inhibitors competitive with L-glutamate for bovine liver glutamate dehydrogenase. The extent of inhibition by the derived compounds was not much greater than that obtained with the parent compound, isophthalic acid. A plot of pKi versus pH showed the presence of an ionizable group (pKa 7.4-7.8) at the enzyme active site which interacted with the substitutent at the 5 position of the substituted isophthalates."}
{"id": "PMID:2936", "title": "Dehydrogenation of reduced pyridine nucleotides by Leydig cell tumors of the rat testis.", "content": "The activities of the cytochrome c reductases and of the D-T diaphorase in rat Leydig cell tumors have been described. The increase in enzymatic activity of the NADH cytochrome c reductase activity in functional tumors derived from interstitial cells of the rat testis is interpreted as being possibly related to hydroxylation of steroids by the neoplastic cells. Meanwhile, the increase in the activity of the D-T diaphorase in the other tumor is interpreted as being an anaplerotic reaction to substitute for the deficient shuttles for the transfer of reducing equivalents from the cytoplasm to the mitochondria observed in tumors.", "contents": "Dehydrogenation of reduced pyridine nucleotides by Leydig cell tumors of the rat testis. The activities of the cytochrome c reductases and of the D-T diaphorase in rat Leydig cell tumors have been described. The increase in enzymatic activity of the NADH cytochrome c reductase activity in functional tumors derived from interstitial cells of the rat testis is interpreted as being possibly related to hydroxylation of steroids by the neoplastic cells. Meanwhile, the increase in the activity of the D-T diaphorase in the other tumor is interpreted as being an anaplerotic reaction to substitute for the deficient shuttles for the transfer of reducing equivalents from the cytoplasm to the mitochondria observed in tumors."}
{"id": "PMID:2937", "title": "The intrinsic, association and commissural connections of area 17 on the visual cortex.", "content": "An experimental neurohistological study has been made of the intrinsic connections of the cortex of area 17 of the monkey, of the commissural connections of the visual cortex of the cat and monkey and of the association fibres passing into area 17 of the cat. In light microscopic studies the axonal degeneration method of Nauta has been used, and the site and mode of termination of the degenerating fibres has also been determined with the electron microscope...", "contents": "The intrinsic, association and commissural connections of area 17 on the visual cortex. An experimental neurohistological study has been made of the intrinsic connections of the cortex of area 17 of the monkey, of the commissural connections of the visual cortex of the cat and monkey and of the association fibres passing into area 17 of the cat. In light microscopic studies the axonal degeneration method of Nauta has been used, and the site and mode of termination of the degenerating fibres has also been determined with the electron microscope..."}
{"id": "PMID:2939", "title": "Stress-induced response of mouse liver tyrosine aminotransferase after irradiation.", "content": "On X-ray irradiated mice with a total dose of 800 R, the reactivity upon an aggressive agent (chloroform stress) administered at various delays after irradiation was studied. The reactivity of the animals has been emphasized by the hepatic induction of the tyrosine aminotransferase and by the adrenal ascorbic acid depletion. From the 3rd day after irradiation both these parameters showed a marked and irreversible decrease.", "contents": "Stress-induced response of mouse liver tyrosine aminotransferase after irradiation. On X-ray irradiated mice with a total dose of 800 R, the reactivity upon an aggressive agent (chloroform stress) administered at various delays after irradiation was studied. The reactivity of the animals has been emphasized by the hepatic induction of the tyrosine aminotransferase and by the adrenal ascorbic acid depletion. From the 3rd day after irradiation both these parameters showed a marked and irreversible decrease."}
{"id": "PMID:2940", "title": "The cross-groin flap for coverage of foot and ankle defects in children. Case reports.", "content": "The cross-groin flap is useful for covering soft tissue defects of the distal portion of the lower limb in a child.", "contents": "The cross-groin flap for coverage of foot and ankle defects in children. Case reports. The cross-groin flap is useful for covering soft tissue defects of the distal portion of the lower limb in a child."}
{"id": "PMID:2942", "title": "[Effects of antianxiety drugs on the food intake in trained and untrained rats and mice (author's transl)].", "content": "Various minor tranquilizers (benzodiazepines, barbiturates and meprobamate) induced an increase in the food intake of rats or mice. Drugs were injected i.p. 30 min before testing and the amount of food consumed during 30 min was recorded. The enhanced food consumption occurred when the animals were in a novel situation, in a situation which they had previously experienced, or in their home cage, in which they were used to eating in the daytime within 30 min. Studies with two benzodiazepines showed this effect to be maximal between 10 to 30 min after injection and to disappear 4 hrs after injection. Moreover, minor tranquilizers reduce the latency before eating of rats and mice tested in a new situation. These results and the observation of anti-anxiety drugs-induced hyperphagia in satiated animals suggest that: 1. The enhanced food consumption of a non familiar food in a novel situation induced by the minor tranquilizers could hardly be related only to their anti-anxiety action. 2. The existence of some inhibitory controls (endogenous satiety in daytime or satiety after recent absorption) is not essential for the action of the minor tranquilizers. 3. An increased motivation and a disruption in the food related behavior could possibly be an explanation for all the observed effects.", "contents": "[Effects of antianxiety drugs on the food intake in trained and untrained rats and mice (author's transl)]. Various minor tranquilizers (benzodiazepines, barbiturates and meprobamate) induced an increase in the food intake of rats or mice. Drugs were injected i.p. 30 min before testing and the amount of food consumed during 30 min was recorded. The enhanced food consumption occurred when the animals were in a novel situation, in a situation which they had previously experienced, or in their home cage, in which they were used to eating in the daytime within 30 min. Studies with two benzodiazepines showed this effect to be maximal between 10 to 30 min after injection and to disappear 4 hrs after injection. Moreover, minor tranquilizers reduce the latency before eating of rats and mice tested in a new situation. These results and the observation of anti-anxiety drugs-induced hyperphagia in satiated animals suggest that: 1. The enhanced food consumption of a non familiar food in a novel situation induced by the minor tranquilizers could hardly be related only to their anti-anxiety action. 2. The existence of some inhibitory controls (endogenous satiety in daytime or satiety after recent absorption) is not essential for the action of the minor tranquilizers. 3. An increased motivation and a disruption in the food related behavior could possibly be an explanation for all the observed effects."}
{"id": "PMID:2943", "title": "LSD as an agonist at mesolimbic dopamine receptors.", "content": "The dopamine agonist apomorphine (1.0 mg/kg i.p.) produced an enhanced stimulation of locomotor activity compared to control animals in rats injected bilaterally 14 days previously with 6-hydroxydopamine (6OHDA) into the nucleus accumbens. (+)-Lysergic acid diethylamide (LSD) also produced a marked stimulation of locomotor activity in the 6OHDA treated animals at a dose (1.0 mg/kg i.p.) which was ineffective in control rats. (+)-Bromo-lysergic acid diethylamide (2.0 mg/kg i.p.) did not stimulate locomotor activity in 6OHDA treated rats. The locomotor stimulation produced by LSD was blocked by pretreatment with the dopamine antagonist pimozide (0.5 mg/kg i.p.). It is suggested that LSD acts as an agonist at mesolimbic dopamine receptors.", "contents": "LSD as an agonist at mesolimbic dopamine receptors. The dopamine agonist apomorphine (1.0 mg/kg i.p.) produced an enhanced stimulation of locomotor activity compared to control animals in rats injected bilaterally 14 days previously with 6-hydroxydopamine (6OHDA) into the nucleus accumbens. (+)-Lysergic acid diethylamide (LSD) also produced a marked stimulation of locomotor activity in the 6OHDA treated animals at a dose (1.0 mg/kg i.p.) which was ineffective in control rats. (+)-Bromo-lysergic acid diethylamide (2.0 mg/kg i.p.) did not stimulate locomotor activity in 6OHDA treated rats. The locomotor stimulation produced by LSD was blocked by pretreatment with the dopamine antagonist pimozide (0.5 mg/kg i.p.). It is suggested that LSD acts as an agonist at mesolimbic dopamine receptors."}
{"id": "PMID:2944", "title": "Effects of various inhibitors of tyrosine hydroxylase and dopamine beta-hydroxylase on rat self-stimulation after reserpine treatment.", "content": "The behavioral effects of low doses of the catecholamine (CA) synthesis inhibitor, alpha-methyl-p-tyrosine (alpha-MPT, 50 mg/kg i.p.), or the norepinephrine (NE) synthesis inhibitors (FLA-63, 15 mg/kg i.p., U-14624, 50 mg/kg i.p., or disulfiram 150 mg/kg i.p.) were studied in rats pretreated with reserpine (1 mg/kg i.p.) 24 h before. Rats were implanted either in the area ventralis tegmenti (AVT) or in the lateral hypothalamus (LH). The modifications of CA synthesis and endogenous CA levels were estimated in a parallel experiment. Reserpine treatment produced a slow decrease in self-stimulation (SS) rates during the first 12 h; SS rates were 85% of control values 24 h after reserpine treatment. Injection of alpha-MPT in reserpine-pretreated rats inhibited SS (85% decrease 3 h after administration either in AVT or LH rats), whereas dopamine beta-hydroxylase inhibition had no great effect on SS. The administration of very low doses of alpha-MPT (20 mg/kg i.p.) to rats treated with reserpine (24 h before) plus FLA-63 (1 h before) induced an important decrease in SS rates in AVT-implanted rats only. The major conclusion is that dopaminergic neurons seem to be involved in AVT and LH SS. The last experiment suggests the involvement of a balance between dopaminergic and noradrenergic neurons in AVT SS.", "contents": "Effects of various inhibitors of tyrosine hydroxylase and dopamine beta-hydroxylase on rat self-stimulation after reserpine treatment. The behavioral effects of low doses of the catecholamine (CA) synthesis inhibitor, alpha-methyl-p-tyrosine (alpha-MPT, 50 mg/kg i.p.), or the norepinephrine (NE) synthesis inhibitors (FLA-63, 15 mg/kg i.p., U-14624, 50 mg/kg i.p., or disulfiram 150 mg/kg i.p.) were studied in rats pretreated with reserpine (1 mg/kg i.p.) 24 h before. Rats were implanted either in the area ventralis tegmenti (AVT) or in the lateral hypothalamus (LH). The modifications of CA synthesis and endogenous CA levels were estimated in a parallel experiment. Reserpine treatment produced a slow decrease in self-stimulation (SS) rates during the first 12 h; SS rates were 85% of control values 24 h after reserpine treatment. Injection of alpha-MPT in reserpine-pretreated rats inhibited SS (85% decrease 3 h after administration either in AVT or LH rats), whereas dopamine beta-hydroxylase inhibition had no great effect on SS. The administration of very low doses of alpha-MPT (20 mg/kg i.p.) to rats treated with reserpine (24 h before) plus FLA-63 (1 h before) induced an important decrease in SS rates in AVT-implanted rats only. The major conclusion is that dopaminergic neurons seem to be involved in AVT and LH SS. The last experiment suggests the involvement of a balance between dopaminergic and noradrenergic neurons in AVT SS."}
{"id": "PMID:2950", "title": "Immunologic phagocytosis by macrophages: effect by stimulation of alpha adrenergic receptors.", "content": "Alpha adrenergic stimulating drugs, metaraminol, norepinephrine, phenylephrine, was found to increase, in vitro, immunological phagocytosis by mice peritoneal macrophages. This effect could be inhibited by dibenamine, a blocking agent. The stimulation by alpha adrenergic agents was similar to that caused by drugs that reduce the intracellular levels of cyclic adenosine monophosphate or by drugs that increase the levels of cyclic guanosine monophosphate.", "contents": "Immunologic phagocytosis by macrophages: effect by stimulation of alpha adrenergic receptors. Alpha adrenergic stimulating drugs, metaraminol, norepinephrine, phenylephrine, was found to increase, in vitro, immunological phagocytosis by mice peritoneal macrophages. This effect could be inhibited by dibenamine, a blocking agent. The stimulation by alpha adrenergic agents was similar to that caused by drugs that reduce the intracellular levels of cyclic adenosine monophosphate or by drugs that increase the levels of cyclic guanosine monophosphate."}
{"id": "PMID:2955", "title": "[Uric acid as electronic acceptor of chicken liver's XDH (author's transl)].", "content": "Uric acid seems to act as an electronic acceptor in the dehydrogenation of hypoxanthine catalyzed by chicken liver's xanthinedehydrogenase (XDH). Oxidation was observed in crude homogenates under anaerobic conditions, although dialyzed homogenates or purified hepatic XDH also induce a similar action either in aerobic or anaerobic conditions. The reaction pH optimum is about 6.0. Xanthine appears to be the only inhibited product of the reaction when its concentration is greater than 1 X 10(-4) M. When hypoxanthine and uric acid concentrations exceed 2 X 10(-3) M and 1 X 10(-4) M, respectively, they induce inhibition by substrate. Purine is a fairly good substrate of XDH when uric acid acts as acceptor. Allopurinol inhibits hypoxanthine oxidation by uric acid in the presence of XDH. XDH also catalyzes the dismutation of xanthine to hypoxanthine and uric acid.", "contents": "[Uric acid as electronic acceptor of chicken liver's XDH (author's transl)]. Uric acid seems to act as an electronic acceptor in the dehydrogenation of hypoxanthine catalyzed by chicken liver's xanthinedehydrogenase (XDH). Oxidation was observed in crude homogenates under anaerobic conditions, although dialyzed homogenates or purified hepatic XDH also induce a similar action either in aerobic or anaerobic conditions. The reaction pH optimum is about 6.0. Xanthine appears to be the only inhibited product of the reaction when its concentration is greater than 1 X 10(-4) M. When hypoxanthine and uric acid concentrations exceed 2 X 10(-3) M and 1 X 10(-4) M, respectively, they induce inhibition by substrate. Purine is a fairly good substrate of XDH when uric acid acts as acceptor. Allopurinol inhibits hypoxanthine oxidation by uric acid in the presence of XDH. XDH also catalyzes the dismutation of xanthine to hypoxanthine and uric acid."}
{"id": "PMID:2956", "title": "Studies on the anoxic inhibition of myocardial protein synthesis.", "content": "The present study demonstrates that exposure of cardiac muscle to high levels of glucose during anoxia appears to retard damage to myocardial protein synthesis. The mechanism of this \"glucose\" effect is glucose-specific and appears related to the intracellular metabolism of glucose by the anoxic myocardium.", "contents": "Studies on the anoxic inhibition of myocardial protein synthesis. The present study demonstrates that exposure of cardiac muscle to high levels of glucose during anoxia appears to retard damage to myocardial protein synthesis. The mechanism of this \"glucose\" effect is glucose-specific and appears related to the intracellular metabolism of glucose by the anoxic myocardium."}
{"id": "PMID:2957", "title": "Phosphatidate phosphohydrolase and palmitoyl coenzyme A hydrolase in cardiac subcellular fractions.", "content": "The characteristics of the two enzymes related to fatty acid esterifaction were studied in order to provide fundamental information leading to further understanding of the control of myocardial glyceride formation. Palmitoyl-CoA hydrolase and phosphatidate phosphohydrolase are both distributed unevenly among heart subcellular fractions. The activity of the latter enzyme in subcellular fractions changes independently in response to Mg2+ addition and in response to thyroid hormone treatment of animals.", "contents": "Phosphatidate phosphohydrolase and palmitoyl coenzyme A hydrolase in cardiac subcellular fractions. The characteristics of the two enzymes related to fatty acid esterifaction were studied in order to provide fundamental information leading to further understanding of the control of myocardial glyceride formation. Palmitoyl-CoA hydrolase and phosphatidate phosphohydrolase are both distributed unevenly among heart subcellular fractions. The activity of the latter enzyme in subcellular fractions changes independently in response to Mg2+ addition and in response to thyroid hormone treatment of animals."}
{"id": "PMID:2958", "title": "Force development of isoproterenol-damaged frog heart muscle in cyanide anoxia.", "content": "From recent experiments it is indicated that in frogs living at +25 degrees C the abnormal response to cyanide anoxia appears as soon as 4-5 hr after the first isoproterenol (IPR) injection, but the aneurysm does not appear until a few hours after the second injection of IPR. There is evidently a discrepancy between the biochemical and structural effects of IPR on the heart. The biochemical effects are probably transient as we have observed that a normal response to cyanide reappears a few weeks after the second IPR injection. It might thus be concluded that IPR causes derangement to the cells also in hearts without any visible lesions and demonstrated as a lowered resistance to histotixic anoxia. This effect precedes any structural damage if such should occur and is of a transient nature.", "contents": "Force development of isoproterenol-damaged frog heart muscle in cyanide anoxia. From recent experiments it is indicated that in frogs living at +25 degrees C the abnormal response to cyanide anoxia appears as soon as 4-5 hr after the first isoproterenol (IPR) injection, but the aneurysm does not appear until a few hours after the second injection of IPR. There is evidently a discrepancy between the biochemical and structural effects of IPR on the heart. The biochemical effects are probably transient as we have observed that a normal response to cyanide reappears a few weeks after the second IPR injection. It might thus be concluded that IPR causes derangement to the cells also in hearts without any visible lesions and demonstrated as a lowered resistance to histotixic anoxia. This effect precedes any structural damage if such should occur and is of a transient nature."}
{"id": "PMID:2959", "title": "The role of H+ in temporary hypoxic contractility failure: different effects of pH on the force decay and on the force recovery after reoxygenation.", "content": "The contractility of isolated ventricle strips of the frog heart (Rana pipiens) was studied under temporary N2 hypoxia and during subsequent recovery after reoxygenation under different extracellular H ion concentrations (pH 6.0-8.5). The recovery of contractile force was three times more pH-sensitive than force decay. Under slow pacing (12/min) at +12 degrees C there was almost complete recovery to control values within 60 min at pHe above 7.0. Under this pH level recovery was largely delayed (pH 6.5) or did not occur (pH 6.0). Prolongation of contraction during the reoxygenation phase, observed at low H ion concentrations, was largely delayed or absent under high concentrations of H ions.", "contents": "The role of H+ in temporary hypoxic contractility failure: different effects of pH on the force decay and on the force recovery after reoxygenation. The contractility of isolated ventricle strips of the frog heart (Rana pipiens) was studied under temporary N2 hypoxia and during subsequent recovery after reoxygenation under different extracellular H ion concentrations (pH 6.0-8.5). The recovery of contractile force was three times more pH-sensitive than force decay. Under slow pacing (12/min) at +12 degrees C there was almost complete recovery to control values within 60 min at pHe above 7.0. Under this pH level recovery was largely delayed (pH 6.5) or did not occur (pH 6.0). Prolongation of contraction during the reoxygenation phase, observed at low H ion concentrations, was largely delayed or absent under high concentrations of H ions."}
{"id": "PMID:2960", "title": "Effect of variations in pH on kinetics of myosin.", "content": "The pH optimum was the same in canine tissue for cardiac and skeletal muscle myosin; when myosin was activated by monovalent cations, the pH optimum was 7.5 while activation of myosin by divalent cations gave a pH optimum of 5.5. Protons were needed for divalent cation activation of myosin. With changes in pH there were concomitant changes in the apparent affinity of enzyme for substrate (S 0.5), such that with a decrease in pH there was an elevation in K+- or NH4+ -activated myosin's apparent affinity for adenosine triphosphate (ATP), and at the same time a decrease in Vmax values of myosin. The converse was true with the divalent cations, Ca++ and Mn++; here with a decrease in pH there was a concomitant decrease in apparent affinity of myosin for ATP, and at the same time an increase in the enzymatic Vmax values. It appeared that hydrogen ions affected the apparent affinity of myosin for substrate and this in turn affected the rate-limiting step in ATPase reaction. Addition of monovalent cations to the divalent cation activating system lowered the activity of myosin, and the converse was true: divalent cations lowered the activity of myosin when activated by monovalent ones in a monovalent cation activating system.", "contents": "Effect of variations in pH on kinetics of myosin. The pH optimum was the same in canine tissue for cardiac and skeletal muscle myosin; when myosin was activated by monovalent cations, the pH optimum was 7.5 while activation of myosin by divalent cations gave a pH optimum of 5.5. Protons were needed for divalent cation activation of myosin. With changes in pH there were concomitant changes in the apparent affinity of enzyme for substrate (S 0.5), such that with a decrease in pH there was an elevation in K+- or NH4+ -activated myosin's apparent affinity for adenosine triphosphate (ATP), and at the same time a decrease in Vmax values of myosin. The converse was true with the divalent cations, Ca++ and Mn++; here with a decrease in pH there was a concomitant decrease in apparent affinity of myosin for ATP, and at the same time an increase in the enzymatic Vmax values. It appeared that hydrogen ions affected the apparent affinity of myosin for substrate and this in turn affected the rate-limiting step in ATPase reaction. Addition of monovalent cations to the divalent cation activating system lowered the activity of myosin, and the converse was true: divalent cations lowered the activity of myosin when activated by monovalent ones in a monovalent cation activating system."}
{"id": "PMID:2961", "title": "Distribution of prostaglandin E 9-ketoreductase and NAD+-dependent and NADP+-dependent 15-hydroxyprostaglandin dehydrogenase in the renal cortex and medulla of various species.", "content": "Regional distributions of PGE 9-ketoreductase and 15-hydroxy-prostaglandin dehydrogenase were examined in the cytoplasmic fractions from the kidneys of seven species. All species contained an NADPH-dependent reductase, as well as NAD+- and NADP+-dependent dehydrogenases in both cortex and medulla. A previously unrecognized cytoplasmic NADH-dependent PGE 9-ketoreductase was also detected in the cortex and medulla of rat and bovine kidney. Total NAD+- and NADP+-dependent dehydrogenase activity was about equally distributed between the two renal regions of monkey, dog, rat, and swine. Bovine, rabbit, and cat had greater cortical than medullary dehydrogenase activity with ratios of 3, 5, and 10 respectively. The activities of NAD+- and NADP+-dependent dehydrogenase varied among the renal tissues.", "contents": "Distribution of prostaglandin E 9-ketoreductase and NAD+-dependent and NADP+-dependent 15-hydroxyprostaglandin dehydrogenase in the renal cortex and medulla of various species. Regional distributions of PGE 9-ketoreductase and 15-hydroxy-prostaglandin dehydrogenase were examined in the cytoplasmic fractions from the kidneys of seven species. All species contained an NADPH-dependent reductase, as well as NAD+- and NADP+-dependent dehydrogenases in both cortex and medulla. A previously unrecognized cytoplasmic NADH-dependent PGE 9-ketoreductase was also detected in the cortex and medulla of rat and bovine kidney. Total NAD+- and NADP+-dependent dehydrogenase activity was about equally distributed between the two renal regions of monkey, dog, rat, and swine. Bovine, rabbit, and cat had greater cortical than medullary dehydrogenase activity with ratios of 3, 5, and 10 respectively. The activities of NAD+- and NADP+-dependent dehydrogenase varied among the renal tissues."}
{"id": "PMID:2962", "title": "Normal blood-gas values in lambs during neonatal development and in adult sheep.", "content": "Arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions and pH were determined in 20 lambs during development from two weeks to five months of age and in 34 adult sheep. Throughout the period the lambs' mean PaCO2 (33.1 mm Hg) and pH (7.46) values were similar to those determined in the adult sheep (PaCO232.1 mm Hg; pH 7.48). The lamb's mean PaO2 increased from 63.3 mm Hg at two weeks of age to about 80 mm Hg at eight weeks and by 20 weeks was similar to the mean PaO2 (88.0 mm Hg) of adult sheep.", "contents": "Normal blood-gas values in lambs during neonatal development and in adult sheep. Arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions and pH were determined in 20 lambs during development from two weeks to five months of age and in 34 adult sheep. Throughout the period the lambs' mean PaCO2 (33.1 mm Hg) and pH (7.46) values were similar to those determined in the adult sheep (PaCO232.1 mm Hg; pH 7.48). The lamb's mean PaO2 increased from 63.3 mm Hg at two weeks of age to about 80 mm Hg at eight weeks and by 20 weeks was similar to the mean PaO2 (88.0 mm Hg) of adult sheep."}
{"id": "PMID:2965", "title": "[The clinical importance of angiography in the diagnosis of periarteritis nodosa].", "content": "Report on a 53 years old patient with renal failure. Angiography showed multiple micro-aneurysms in kidneys and liver, in some instances also in the pancreatic, duodenal and mesenterial arteries. Muscle biopsy confirmed the suspicion of arteriitis nodosa. Clinically the diagnosis of necrotizing arteriitis is difficult. Angiography settles the diagnosis, but only positive findings of micro-aneurysms prove it. The differential diagnosis is discussed and illustrated.", "contents": "[The clinical importance of angiography in the diagnosis of periarteritis nodosa]. Report on a 53 years old patient with renal failure. Angiography showed multiple micro-aneurysms in kidneys and liver, in some instances also in the pancreatic, duodenal and mesenterial arteries. Muscle biopsy confirmed the suspicion of arteriitis nodosa. Clinically the diagnosis of necrotizing arteriitis is difficult. Angiography settles the diagnosis, but only positive findings of micro-aneurysms prove it. The differential diagnosis is discussed and illustrated."}
{"id": "PMID:2967", "title": "pH and the cytotoxicity of fluoride in an animal cell culture system.", "content": "To investigate the mechanism for the toxicity of silicate cement as observed in a cell culture system, the effects of pH and fluoride were tested on human epithelial cells (NCTC 2544). At pH 7.3, fluoride concentrations from 15 to 25 mug/ml (0.79 to 1.3 mM) had a growth inhibitory effect. When pH of the incubation medium was lowered in the range 7.0 to 6.4, an enhanced cytoxic effect of fluoride was found, and even at 5 to 10 mug/ml growth inhibition occurred. Concomitant with the enhanced cytotoxicity of fluoride at low pH, there was an increased utilization of glucose and formation of lactate. Upon lowering the pH of the incubation medium from 7.4 to 6.7 a twofold increase in the intracellular concentration of fluoride was found.", "contents": "pH and the cytotoxicity of fluoride in an animal cell culture system. To investigate the mechanism for the toxicity of silicate cement as observed in a cell culture system, the effects of pH and fluoride were tested on human epithelial cells (NCTC 2544). At pH 7.3, fluoride concentrations from 15 to 25 mug/ml (0.79 to 1.3 mM) had a growth inhibitory effect. When pH of the incubation medium was lowered in the range 7.0 to 6.4, an enhanced cytoxic effect of fluoride was found, and even at 5 to 10 mug/ml growth inhibition occurred. Concomitant with the enhanced cytotoxicity of fluoride at low pH, there was an increased utilization of glucose and formation of lactate. Upon lowering the pH of the incubation medium from 7.4 to 6.7 a twofold increase in the intracellular concentration of fluoride was found."}
{"id": "PMID:2968", "title": "Dysplasia of the testis and epididymis.", "content": "Various congenital malformations of the testis and the seminal pathways are illustrated by 10 cases. Though these malformations are often free from symptoms, an increasing number of them are now being discovered in connection with investigations of male infertility. In cases of azoospermia where testicular biopsies show complete spermatogenesis, surgical exploration is indicated. Some of these malformations may then be treated by surgery, with fairly good prospects of restored fertility.", "contents": "Dysplasia of the testis and epididymis. Various congenital malformations of the testis and the seminal pathways are illustrated by 10 cases. Though these malformations are often free from symptoms, an increasing number of them are now being discovered in connection with investigations of male infertility. In cases of azoospermia where testicular biopsies show complete spermatogenesis, surgical exploration is indicated. Some of these malformations may then be treated by surgery, with fairly good prospects of restored fertility."}
{"id": "PMID:2969", "title": "[Lipoprotein X in hepatobiliary diseases].", "content": "The diagnostic and prognostic reliability of lipoprotein-X (Lp-X) in demonstrating or ruling out cholestasis has been evaluated in a group of 80 patients with diseases of the liver and/or the biliary tracts, and in 103 subjects with various other diseases. The results of Lp-X detection were compared with the so-called \"enzymes indicating cholestasis\": alkaline phosphatase, leucine arylamidase, and gamma-glutamyltranspeptidase. Where possible a histologic specimen of the liver was obtained. The correlation between Lp-X and \"enzymes indicating cholestasis\" was satisfactory in more than 90% of cases. When compared with the histologic findings, Lp-X proved to be more reliable than the enzymes. Despite this fact, Lp-X did not show absolute specifity in the detection of cholestasis as there were several negative results in cases with histologically proven cholestasis. Furthermore, the differentiation of intra- and extrahepatic cholestasis was not possible on the basis of Lp-X. In the control group of 103 patients with other than hepatobiliary diseases, a positive Lp-X result was found in 3 cases. Further investigations in these three patients revealed that primarily unsuspected hepatobiliary disease could not be ruled out. In the follow-up of a hepatobiliary disease the transition of Lp-X to negative indicates a trend towards improvement of cholestasis 1-2 weeks earlier than the enzymes mentioned above.", "contents": "[Lipoprotein X in hepatobiliary diseases]. The diagnostic and prognostic reliability of lipoprotein-X (Lp-X) in demonstrating or ruling out cholestasis has been evaluated in a group of 80 patients with diseases of the liver and/or the biliary tracts, and in 103 subjects with various other diseases. The results of Lp-X detection were compared with the so-called \"enzymes indicating cholestasis\": alkaline phosphatase, leucine arylamidase, and gamma-glutamyltranspeptidase. Where possible a histologic specimen of the liver was obtained. The correlation between Lp-X and \"enzymes indicating cholestasis\" was satisfactory in more than 90% of cases. When compared with the histologic findings, Lp-X proved to be more reliable than the enzymes. Despite this fact, Lp-X did not show absolute specifity in the detection of cholestasis as there were several negative results in cases with histologically proven cholestasis. Furthermore, the differentiation of intra- and extrahepatic cholestasis was not possible on the basis of Lp-X. In the control group of 103 patients with other than hepatobiliary diseases, a positive Lp-X result was found in 3 cases. Further investigations in these three patients revealed that primarily unsuspected hepatobiliary disease could not be ruled out. In the follow-up of a hepatobiliary disease the transition of Lp-X to negative indicates a trend towards improvement of cholestasis 1-2 weeks earlier than the enzymes mentioned above."}
{"id": "PMID:2970", "title": "[Proceedings: Home treatment of chronic respiratory insufficiency: inhalation of beta stimulators].", "content": "In the author's experience, the longterm treatment of chronic obstructive lung disease should be supplemented by continuous selective stimulation of the adrenergic beta-receptors in the smooth bronchial muscles. The following procedure is recommended: inhalation of 15 min 3 times daily using an adequate aerosol with a powered nebulizer (Pari-Privat), with 2-3 ml Tyloxapol carrier solution or saline with 5 drops salbutamol.", "contents": "[Proceedings: Home treatment of chronic respiratory insufficiency: inhalation of beta stimulators]. In the author's experience, the longterm treatment of chronic obstructive lung disease should be supplemented by continuous selective stimulation of the adrenergic beta-receptors in the smooth bronchial muscles. The following procedure is recommended: inhalation of 15 min 3 times daily using an adequate aerosol with a powered nebulizer (Pari-Privat), with 2-3 ml Tyloxapol carrier solution or saline with 5 drops salbutamol."}
{"id": "PMID:2971", "title": "[Proceedings: Long-term therapy with antibiotics in chronic bronchitis].", "content": "Longterm therapy of chronic bacterial bronchitis assumes two forms: (a) therapy of acute exacerbations, and (b) continuous longterm prophylaxis, chiefly during the 4-7 winter months. Longterm prophylaxis should be confined exclusively to patients with two or more severe annual exacerbations. The commonest pathogens, Haemophilus influenzae and pneumococci, are usually sensitive to ampicillin and amoxycillin, cotrimoxazole (Bactrim or Eusaprim) and tetracyclines.", "contents": "[Proceedings: Long-term therapy with antibiotics in chronic bronchitis]. Longterm therapy of chronic bacterial bronchitis assumes two forms: (a) therapy of acute exacerbations, and (b) continuous longterm prophylaxis, chiefly during the 4-7 winter months. Longterm prophylaxis should be confined exclusively to patients with two or more severe annual exacerbations. The commonest pathogens, Haemophilus influenzae and pneumococci, are usually sensitive to ampicillin and amoxycillin, cotrimoxazole (Bactrim or Eusaprim) and tetracyclines."}
{"id": "PMID:2972", "title": "[Isolation, identification and quantitative determination of lysolecithin in the human gastric juice].", "content": "Lysolecithin was isolated and identified from the gastric contents of 5 patients with gastric ulcer and erosive and atrophic gastritis. The methods used involved methanolic extration, column chromatography on silica gel and sephadex gel filtration, followed by preparative thin layer chromatography. Identification of lysolecithin was verified in one sample by thin layer chromatography and elementary analysis. A method for quantitation of lysolecithin in human gastric fluid for routine clinical analysis is described, based on the procedure used for identification of this phospholipid. Further, a hemolysis test is proposed for screening gastric contents for lysolecithin concentrations above approximately 10 mg/100 ml. With the quantitative method, an average concentration of 66.1 mg of lysolecithin in 100 ml gastric content was found in the group of 5 patients. The screening test was positive in all 5 samples, but was negative with native gastric juice in 25 persons serving as controls. When the gastric fluid of the controls was concentrated, however, 9 samples gave a positive hemolytic reaction. From these 9 specimens, the lysolecithin concentration was found to average 0.9 mg/100 ml. These findings afford evidence that lysolecithin may be involved as a factor in the pathogenesis of gastric ulceration.", "contents": "[Isolation, identification and quantitative determination of lysolecithin in the human gastric juice]. Lysolecithin was isolated and identified from the gastric contents of 5 patients with gastric ulcer and erosive and atrophic gastritis. The methods used involved methanolic extration, column chromatography on silica gel and sephadex gel filtration, followed by preparative thin layer chromatography. Identification of lysolecithin was verified in one sample by thin layer chromatography and elementary analysis. A method for quantitation of lysolecithin in human gastric fluid for routine clinical analysis is described, based on the procedure used for identification of this phospholipid. Further, a hemolysis test is proposed for screening gastric contents for lysolecithin concentrations above approximately 10 mg/100 ml. With the quantitative method, an average concentration of 66.1 mg of lysolecithin in 100 ml gastric content was found in the group of 5 patients. The screening test was positive in all 5 samples, but was negative with native gastric juice in 25 persons serving as controls. When the gastric fluid of the controls was concentrated, however, 9 samples gave a positive hemolytic reaction. From these 9 specimens, the lysolecithin concentration was found to average 0.9 mg/100 ml. These findings afford evidence that lysolecithin may be involved as a factor in the pathogenesis of gastric ulceration."}
{"id": "PMID:2973", "title": "[Prinzmetal angina: clinical aspects and coronarographic findings].", "content": "The clinical course and coronary arteriographic findings in 5 patients with Prinzmetal's variant angina pectoris are reviewed. In 4 patients who had ST-elevations inferiorly, 1 had minimal, 1 only slight, and 1 medium coronary artery disease; 1 had coronary spasm. 1 patient with ST-elevation anteriorly had severe stenosis of the anterior descending coronary artery. All 5 patients had normal left ventriculograms, 3 also had normal left enddiastolic pressure, and 2 slight elevation. Medical treatment was carried out in 2 patients and surgical revascularization in 2. Both treatments were accompanied by marked symptomatic improvement. Spontaneous loss of angina occurred in 1 patient. Prinzmetal's variant angina pectoris may be accompanied by a variety of coronary arteriographic findings and the prognosis appears to be more favorable than previously reported.", "contents": "[Prinzmetal angina: clinical aspects and coronarographic findings]. The clinical course and coronary arteriographic findings in 5 patients with Prinzmetal's variant angina pectoris are reviewed. In 4 patients who had ST-elevations inferiorly, 1 had minimal, 1 only slight, and 1 medium coronary artery disease; 1 had coronary spasm. 1 patient with ST-elevation anteriorly had severe stenosis of the anterior descending coronary artery. All 5 patients had normal left ventriculograms, 3 also had normal left enddiastolic pressure, and 2 slight elevation. Medical treatment was carried out in 2 patients and surgical revascularization in 2. Both treatments were accompanied by marked symptomatic improvement. Spontaneous loss of angina occurred in 1 patient. Prinzmetal's variant angina pectoris may be accompanied by a variety of coronary arteriographic findings and the prognosis appears to be more favorable than previously reported."}
{"id": "PMID:2974", "title": "[Forms of so-called crytorchism. Studies on 579 patients].", "content": "In a material of 579 patients the incidence of the different forms of cryptorchism is investigated. The findings reveal retractile testes in 16.4%, ectopic testes in 23.1%, inguinal retentions in 49.5%, abdominal retentions in 2.3% secondary cryptorchism in 3.5%, and monorchism and anorchism in 4.9%. These results are compared with those of other authors.", "contents": "[Forms of so-called crytorchism. Studies on 579 patients]. In a material of 579 patients the incidence of the different forms of cryptorchism is investigated. The findings reveal retractile testes in 16.4%, ectopic testes in 23.1%, inguinal retentions in 49.5%, abdominal retentions in 2.3% secondary cryptorchism in 3.5%, and monorchism and anorchism in 4.9%. These results are compared with those of other authors."}
{"id": "PMID:2975", "title": "[Sugar-free, tooth-protecting chewing gum and candy. Results of a 7-year study].", "content": "Experiences of 7 years with sugarless chewing gums and lozenges (tab. I and II) regarding their tooth protective properties are reported. Telemetry of interproximal plaque pH allows to assess acid formation from carbohydrates by plaque bacteria under almost natural conditions. Altogether, 5 chewing gums and 8 lozenges containing sorbitol or mixtures of sorbitol and hydrogenated oligosaccharides were investigated. Lowest pH values during and after chewing sugarless gums varied between pH 6.0 and 7.3. When sucking sugarless lozenges the recorded pH values were between 5.8 and 7.0. In contrast to lozenges, the consumption of sugarless chewing gums becomes particularly important due to their greater stimulation of saliva and buffering capacity of oral fluid. All products tested did not acidify interproximal plaque below the critical pH and therefore comply with the regulations of the Swiss Federal Health Authorities with respect to the labeling or marketed sweets with \"safe for teeth\". New non-fermentable sugar-replacing substrates are being developed. Their utilization in foodstuffs and sweets is being discussed.", "contents": "[Sugar-free, tooth-protecting chewing gum and candy. Results of a 7-year study]. Experiences of 7 years with sugarless chewing gums and lozenges (tab. I and II) regarding their tooth protective properties are reported. Telemetry of interproximal plaque pH allows to assess acid formation from carbohydrates by plaque bacteria under almost natural conditions. Altogether, 5 chewing gums and 8 lozenges containing sorbitol or mixtures of sorbitol and hydrogenated oligosaccharides were investigated. Lowest pH values during and after chewing sugarless gums varied between pH 6.0 and 7.3. When sucking sugarless lozenges the recorded pH values were between 5.8 and 7.0. In contrast to lozenges, the consumption of sugarless chewing gums becomes particularly important due to their greater stimulation of saliva and buffering capacity of oral fluid. All products tested did not acidify interproximal plaque below the critical pH and therefore comply with the regulations of the Swiss Federal Health Authorities with respect to the labeling or marketed sweets with \"safe for teeth\". New non-fermentable sugar-replacing substrates are being developed. Their utilization in foodstuffs and sweets is being discussed."}
{"id": "PMID:2978", "title": "[Churg-Strauss syndrome. Its nosological place. Apropos of a new case diagnosed before death].", "content": "Allergic granulomatous angeitis or Churg and Strauss disease, seems to form part of the disease of necrotising angeitis. Clinically, it may be considered when periarteritis nodosa is associated with asthma and marked eosinophilia. The diagnosis depends on the pathological findings including the venous and pulmonary lesions, giant cells and the presence of extra-vascular granulomas. The recognition of this disease does not, however, permit one to give a precise prognosis. In the absence of progress concerning the pathogenesis, treatment will be the same as that given in other forms of necrotising angeitis.", "contents": "[Churg-Strauss syndrome. Its nosological place. Apropos of a new case diagnosed before death]. Allergic granulomatous angeitis or Churg and Strauss disease, seems to form part of the disease of necrotising angeitis. Clinically, it may be considered when periarteritis nodosa is associated with asthma and marked eosinophilia. The diagnosis depends on the pathological findings including the venous and pulmonary lesions, giant cells and the presence of extra-vascular granulomas. The recognition of this disease does not, however, permit one to give a precise prognosis. In the absence of progress concerning the pathogenesis, treatment will be the same as that given in other forms of necrotising angeitis."}
{"id": "PMID:2979", "title": "[Periarteritis nodosa and cancer. Apropos of 2 cases].", "content": "The authors report two cases of periarteritis nodosa associated with carcinoma. The first case was a man with an anaplastic bronchial carcinoma, the second was a woman with a rectal adenocarcinoma. Study of the association of certain collagen diseases with carcinoma was made to emphasize the great rareness of this association.", "contents": "[Periarteritis nodosa and cancer. Apropos of 2 cases]. The authors report two cases of periarteritis nodosa associated with carcinoma. The first case was a man with an anaplastic bronchial carcinoma, the second was a woman with a rectal adenocarcinoma. Study of the association of certain collagen diseases with carcinoma was made to emphasize the great rareness of this association."}
{"id": "PMID:2982", "title": "Nonsurgical control of massive acute gastric mucosal hemorrhage with antacid neutralization of gastric content.", "content": "A simple and safe method of medical treatment for control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from the observation that gastric HCl played a central role in peretuating the syndrome. The treatment consists in neutralization of the gastric acid with antacid to pH of 7.0. In preliminary observations of consecutive admissions, 19 of 20 (95 per cent) patients treated with this techinique stopped bleeding. The one remaining patient required surgery. There were no deaths. In contrast, 10 of 15 (66 per cent) patients stopped bleeding with conventional medical therapy. Four of the remaining patients required surgery to control the bleeding. One patient did not stop on medical management. All five (33 per cent) patients died.", "contents": "Nonsurgical control of massive acute gastric mucosal hemorrhage with antacid neutralization of gastric content. A simple and safe method of medical treatment for control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from the observation that gastric HCl played a central role in peretuating the syndrome. The treatment consists in neutralization of the gastric acid with antacid to pH of 7.0. In preliminary observations of consecutive admissions, 19 of 20 (95 per cent) patients treated with this techinique stopped bleeding. The one remaining patient required surgery. There were no deaths. In contrast, 10 of 15 (66 per cent) patients stopped bleeding with conventional medical therapy. Four of the remaining patients required surgery to control the bleeding. One patient did not stop on medical management. All five (33 per cent) patients died."}
{"id": "PMID:2994", "title": "Effect of total gastrectomy on acid proteolytic zymogens in serum and urine.", "content": "Proteolytic pH-activity curve and agar gel electrophoretic pattern of acid proteolytic zymogens in serum and urine were studied in totally gastrectomized patients. In serum, total gastrectomy was found to reduce proteolytic activity markedly, but no appreciable changes could be detected by electrophoretic analysis. In urine, however, in addition to the marked reduction of proteolytic activity, changes were found in electrophoretic pattern after total gastrectomy. Namely, fraction Pg 3 tended to persist, while Pg 5 disappeared along with the lapse of time after total gastrectomy. An unusual appearance of fraction Pg 7 in urine was also observed on the occasion of postoperative transient albuminuria. Their orgins and related clinical problems were discussed.", "contents": "Effect of total gastrectomy on acid proteolytic zymogens in serum and urine. Proteolytic pH-activity curve and agar gel electrophoretic pattern of acid proteolytic zymogens in serum and urine were studied in totally gastrectomized patients. In serum, total gastrectomy was found to reduce proteolytic activity markedly, but no appreciable changes could be detected by electrophoretic analysis. In urine, however, in addition to the marked reduction of proteolytic activity, changes were found in electrophoretic pattern after total gastrectomy. Namely, fraction Pg 3 tended to persist, while Pg 5 disappeared along with the lapse of time after total gastrectomy. An unusual appearance of fraction Pg 7 in urine was also observed on the occasion of postoperative transient albuminuria. Their orgins and related clinical problems were discussed."}
{"id": "PMID:2995", "title": "[Pollen diet as an adjuvans of radiotherapy in gynecologic carcinomas].", "content": "The introduction of a pollen diet as an adjuvant in the reduction of side effects during radiotherapy of patients with gynaecological cancer is described and its efficacy evaluated. 15 women with carcinoma of the cervix received a pollen diet during irradiation, whilst ten further patients receiving irradiation served as controls without pollen added to the diet. Serum enzymes, proteins, vitamins and blood count were analysed before and after irradiation. It appears, that pollen favourably influences the efficacy of irradiation and reduces the frequency of side effects, both subjectively and objectively.", "contents": "[Pollen diet as an adjuvans of radiotherapy in gynecologic carcinomas]. The introduction of a pollen diet as an adjuvant in the reduction of side effects during radiotherapy of patients with gynaecological cancer is described and its efficacy evaluated. 15 women with carcinoma of the cervix received a pollen diet during irradiation, whilst ten further patients receiving irradiation served as controls without pollen added to the diet. Serum enzymes, proteins, vitamins and blood count were analysed before and after irradiation. It appears, that pollen favourably influences the efficacy of irradiation and reduces the frequency of side effects, both subjectively and objectively."}
{"id": "PMID:2996", "title": "[Effects of lethal overexposure on gastric secretion in the pig].", "content": "The characteristics of gastric secretion following acute gamma exposure (1500 rd) were studied in pigs with a small Pavlov stomach. Spontaneous secretion was practically inhibited when the animals were taken out of the irradiation cell. It slowly recovered in the following hours and its pH, first neutral, turned acid again. However, till the third day, it did not recover normal characteristics. The excretion of sodium ions was much increased. Under histaminic stimulation, the responses of irradiated pigs and controls were much similar. The secretory capacities of the gastric mucosa were retained but without spontaneous manifestations. As a conclusion, the early troubles following overexposure must be the consequences of regulation disorders rather than of the direct action of radiation on the stomach.", "contents": "[Effects of lethal overexposure on gastric secretion in the pig]. The characteristics of gastric secretion following acute gamma exposure (1500 rd) were studied in pigs with a small Pavlov stomach. Spontaneous secretion was practically inhibited when the animals were taken out of the irradiation cell. It slowly recovered in the following hours and its pH, first neutral, turned acid again. However, till the third day, it did not recover normal characteristics. The excretion of sodium ions was much increased. Under histaminic stimulation, the responses of irradiated pigs and controls were much similar. The secretory capacities of the gastric mucosa were retained but without spontaneous manifestations. As a conclusion, the early troubles following overexposure must be the consequences of regulation disorders rather than of the direct action of radiation on the stomach."}
{"id": "PMID:2997", "title": "A study of the host selection patterns of the mosquitoes of the Kisumu area of Kenya.", "content": "The results of 12,168 precipitin tests on blood meals of mosquitoes of the Kano Plain caught by a variety of catching techniques indicate that to gain an accurate overall picture of feeding patterns both the indoor and the outdoor biotope must be sampled. CDC light traps operated inside houses and Monkswood type light traps operated under the outside eaves of houses were found to collect larger numbers of blood fed specimens from a wider range of species than battery driven aspirators collecting from natural resting sites. The results indicated that 7 mosquito species entered houses to bite man in appreciable numbers in the Kisumu area. These were Anopheles gambiae s.l., A. funestus, A. pharoensis, Mansonia uniformia, M. africana, Culex antennatus, and C. univittatus. Eight mosquito species were found to bite man and domestic animals in the outdoor biotope in large numbers. These were: A. pharoensis, A. ziemanni, M. uniformis, M. africana, C. antennatus, C. univittatus, Aedes circumluteolus, and Ae. ochraceus. From an epidemiological point of view, species with a narrow range of hosts are most likely to be of importance as vectors of parasitic diseases such as malaria and into this category fall the major man biting anophelines A. gambiae and A. funestus. Those mosquito species which switch from one group of hosts to another according to local circumstances are most likely to be involved in arbovirus transmission and in this group the following species must be considered: A. pharoensis, A. ziemanni, M. uniformia, M. africana, C. antennatus, C. univittatus and Ae. circumluteolus.", "contents": "A study of the host selection patterns of the mosquitoes of the Kisumu area of Kenya. The results of 12,168 precipitin tests on blood meals of mosquitoes of the Kano Plain caught by a variety of catching techniques indicate that to gain an accurate overall picture of feeding patterns both the indoor and the outdoor biotope must be sampled. CDC light traps operated inside houses and Monkswood type light traps operated under the outside eaves of houses were found to collect larger numbers of blood fed specimens from a wider range of species than battery driven aspirators collecting from natural resting sites. The results indicated that 7 mosquito species entered houses to bite man in appreciable numbers in the Kisumu area. These were Anopheles gambiae s.l., A. funestus, A. pharoensis, Mansonia uniformia, M. africana, Culex antennatus, and C. univittatus. Eight mosquito species were found to bite man and domestic animals in the outdoor biotope in large numbers. These were: A. pharoensis, A. ziemanni, M. uniformis, M. africana, C. antennatus, C. univittatus, Aedes circumluteolus, and Ae. ochraceus. From an epidemiological point of view, species with a narrow range of hosts are most likely to be of importance as vectors of parasitic diseases such as malaria and into this category fall the major man biting anophelines A. gambiae and A. funestus. Those mosquito species which switch from one group of hosts to another according to local circumstances are most likely to be involved in arbovirus transmission and in this group the following species must be considered: A. pharoensis, A. ziemanni, M. uniformia, M. africana, C. antennatus, C. univittatus and Ae. circumluteolus."}
{"id": "PMID:3001", "title": "The host component of the graft-versus-host reaction. A study on the popliteal lymph node reaction in the rat.", "content": "I have measured the proportion of host cells in a popliteal lymph node undergoing a graft-versus-host (GVH) reaction. By using cytotoxic alloantisera with specificity for donor and host Ag-B determined antigens, it was found that about 90% of live cells suspended from the node were of host origin. The role of host T lymphocytes in this reaction was evaluated by investigating GVH-reactivity in hosts depleted of T cells (B rats). These rats differed very little from normal hosts with regard to lymph node weight increase (which was, in fact, slightly enhanced), increase in node cellularity, and donor/host contribution. The number of i.v. infused 51Cr-labelled thoracic duct lymphocytes localizing in popliteal lymph nodes undergoing a GVH-reaction was increased, but the significance of this phenomenon for the lymph node enlargement is questionable.", "contents": "The host component of the graft-versus-host reaction. A study on the popliteal lymph node reaction in the rat. I have measured the proportion of host cells in a popliteal lymph node undergoing a graft-versus-host (GVH) reaction. By using cytotoxic alloantisera with specificity for donor and host Ag-B determined antigens, it was found that about 90% of live cells suspended from the node were of host origin. The role of host T lymphocytes in this reaction was evaluated by investigating GVH-reactivity in hosts depleted of T cells (B rats). These rats differed very little from normal hosts with regard to lymph node weight increase (which was, in fact, slightly enhanced), increase in node cellularity, and donor/host contribution. The number of i.v. infused 51Cr-labelled thoracic duct lymphocytes localizing in popliteal lymph nodes undergoing a GVH-reaction was increased, but the significance of this phenomenon for the lymph node enlargement is questionable."}
{"id": "PMID:3002", "title": "Arboviruses isolated from mosquitos and man in Surinam.", "content": "In the capital of Surinam, and in parts of the coastal plain and the savannah belt 47 strains of arbovirus were isolated from mosquito pools and from sentinel mice. Most of the strains (51%) were of the Mucambo type. The other types were Guama, Bimiti, Una, Catu, Restan, Maru, and Kwatta. Culex portesi was found to be the principal vector of all but one (Maru) types. Other vectors found to be carriers of arboviruses were Psorophora ferox, Mansonia venezuelensis, and A\u00ebdes serratus. The highest proportion of mosquito pools yielding arboviruses was found in the savannah belt, the lowest in the municipality of Paramaribo.", "contents": "Arboviruses isolated from mosquitos and man in Surinam. In the capital of Surinam, and in parts of the coastal plain and the savannah belt 47 strains of arbovirus were isolated from mosquito pools and from sentinel mice. Most of the strains (51%) were of the Mucambo type. The other types were Guama, Bimiti, Una, Catu, Restan, Maru, and Kwatta. Culex portesi was found to be the principal vector of all but one (Maru) types. Other vectors found to be carriers of arboviruses were Psorophora ferox, Mansonia venezuelensis, and A\u00ebdes serratus. The highest proportion of mosquito pools yielding arboviruses was found in the savannah belt, the lowest in the municipality of Paramaribo."}
{"id": "PMID:2999", "title": "The use of pluronic polyols in the precipitation of plasma proteins and its application in the preparation of plasma derivatives.", "content": "Pluronic F-38 was used a precipitant of plasma proteins under varying conditions of pH and polymer concentration. Results indicated that marked differences in the solubility of the plasma proteins in F-38 solutions can be appled to the separation of plasma components. The feasibility of the industrial application of this fractionation method was tested in several experiments. Conditions were established for the preparation of albumin, human plasma protein fraction (HPPF), and immune serum globulin (ISG) with similar yield and purity as those prepared by the Cohn methods. Current procedures for the preparation of antihemophilic A (Facor VIII) concentrate and prothrombin complex (Factors II, VII, IX, and X) were adapted to the F-38 process by removal of the clotting factors from the starting plasma prior to polymer precipitation. In addition, a plasma protein solution free of lipoproteins, isoagglutinins, and clotting factors was developed which has proven useful as a perfusion medium in organ preservation.", "contents": "The use of pluronic polyols in the precipitation of plasma proteins and its application in the preparation of plasma derivatives. Pluronic F-38 was used a precipitant of plasma proteins under varying conditions of pH and polymer concentration. Results indicated that marked differences in the solubility of the plasma proteins in F-38 solutions can be appled to the separation of plasma components. The feasibility of the industrial application of this fractionation method was tested in several experiments. Conditions were established for the preparation of albumin, human plasma protein fraction (HPPF), and immune serum globulin (ISG) with similar yield and purity as those prepared by the Cohn methods. Current procedures for the preparation of antihemophilic A (Facor VIII) concentrate and prothrombin complex (Factors II, VII, IX, and X) were adapted to the F-38 process by removal of the clotting factors from the starting plasma prior to polymer precipitation. In addition, a plasma protein solution free of lipoproteins, isoagglutinins, and clotting factors was developed which has proven useful as a perfusion medium in organ preservation."}
{"id": "PMID:3000", "title": "Preparation and storage of platelet concentrates.", "content": "A technique of platelet concentrate preparation and storage is presented which permits the maximum number of viable and functional platelets to be preserved for periods of 72 hours. Although the storage conditions must be followed precisely, the method is nevertheless simple to perform and does not require specialized expensive equipment. Critical factors include: 1) preparation of the platelet concentrates with an initial centrifugation of 1000 X g for 9 minutes and a second centrifugation of 3000 X g for 20 minutes (86% +/- 1 platelet yield), 2) a storage bag composed of either Fenwal's PL-146 or McGaw plastic, 3) constant gentle mixing, 4) a 70 ml residual plasma volume, and 5) room temperature storage (22 C +/- 2). In Vivo platelet recovery after 72 hours of storage at room temperature averaged 46 per cent +/- 3 and survival was 7.9 days +/- 0.3 (81% of fresh platelet viability). The function of these platelets as measured by the correlation between bleeding time and platelet count after transfusion of pooled platelets into unimmunized, aplastic thrombocytopenic recipients was as good as that of fresh platelets. Both viability and function of concentrated platelets stored at 4 C are severely compromised.", "contents": "Preparation and storage of platelet concentrates. A technique of platelet concentrate preparation and storage is presented which permits the maximum number of viable and functional platelets to be preserved for periods of 72 hours. Although the storage conditions must be followed precisely, the method is nevertheless simple to perform and does not require specialized expensive equipment. Critical factors include: 1) preparation of the platelet concentrates with an initial centrifugation of 1000 X g for 9 minutes and a second centrifugation of 3000 X g for 20 minutes (86% +/- 1 platelet yield), 2) a storage bag composed of either Fenwal's PL-146 or McGaw plastic, 3) constant gentle mixing, 4) a 70 ml residual plasma volume, and 5) room temperature storage (22 C +/- 2). In Vivo platelet recovery after 72 hours of storage at room temperature averaged 46 per cent +/- 3 and survival was 7.9 days +/- 0.3 (81% of fresh platelet viability). The function of these platelets as measured by the correlation between bleeding time and platelet count after transfusion of pooled platelets into unimmunized, aplastic thrombocytopenic recipients was as good as that of fresh platelets. Both viability and function of concentrated platelets stored at 4 C are severely compromised."}
{"id": "PMID:3003", "title": "[Polysome ribonucleases of leukemic cells].", "content": "The composition of ribosomal proteins isolated from normal homopoietic and leucemic cells was studied by analytic electrophoresis in polyacrylamide gel. It was found that acid-soluble proteins from polysomal complexes can be separated into 21-22 components in the acid system. There was no significant differences in protein components from normal and leucemic polysomes by their quantity and mobility in polyacrylamide gel. Five protein components possess a ribonuclease activity as it was established by using technique of direct RNase assay in electrophoregrams. All ribonuclease-active components have pH optimum at 7.6-7.8. No differences were detected in the number and activity of particular enzyme components of polysomes isolated from normal hemopoietic and leucemic tissues. It is suggested that the number and presence of RNases in polysome complexes is likely to play not a significant role in regulation of polysome activity, but influence of inhibitors makes this supposition possible.", "contents": "[Polysome ribonucleases of leukemic cells]. The composition of ribosomal proteins isolated from normal homopoietic and leucemic cells was studied by analytic electrophoresis in polyacrylamide gel. It was found that acid-soluble proteins from polysomal complexes can be separated into 21-22 components in the acid system. There was no significant differences in protein components from normal and leucemic polysomes by their quantity and mobility in polyacrylamide gel. Five protein components possess a ribonuclease activity as it was established by using technique of direct RNase assay in electrophoregrams. All ribonuclease-active components have pH optimum at 7.6-7.8. No differences were detected in the number and activity of particular enzyme components of polysomes isolated from normal hemopoietic and leucemic tissues. It is suggested that the number and presence of RNases in polysome complexes is likely to play not a significant role in regulation of polysome activity, but influence of inhibitors makes this supposition possible."}
{"id": "PMID:3004", "title": "[Comparative characteristics of catalase from the fungus Penicillium vitale, which is synthesized under different nutritional conditions].", "content": "A comparative study of properties (absorption spectra, thermostability, pH optimum, polyacrylamide gel electrophoresis, DEAE-cellulose separation) and structure (amino acid composition, finger-prints, carbohydrate composition) was performed for P. vitale catalase synthesized under different medium conditions. In all cases the results were similar. The only difference occured in the amount of synthesized proteins. A conclusion is drawn that under different nourishing conditions of the fungus the properties and structure of the catalase are unchanged, but the regulatory mechanisms of catalase and glucosooxidate synthesis undergo changes.", "contents": "[Comparative characteristics of catalase from the fungus Penicillium vitale, which is synthesized under different nutritional conditions]. A comparative study of properties (absorption spectra, thermostability, pH optimum, polyacrylamide gel electrophoresis, DEAE-cellulose separation) and structure (amino acid composition, finger-prints, carbohydrate composition) was performed for P. vitale catalase synthesized under different medium conditions. In all cases the results were similar. The only difference occured in the amount of synthesized proteins. A conclusion is drawn that under different nourishing conditions of the fungus the properties and structure of the catalase are unchanged, but the regulatory mechanisms of catalase and glucosooxidate synthesis undergo changes."}
{"id": "PMID:3014", "title": "Suprapubic paramedian laparotomy for equine abdominal cryptorchidism.", "content": "The history of techniques for abdominal equine cryptorchidectomy is briefly reviewed. The technique of suprapubic paramedian laparotomy as used since 1955 at the University of Liverpool veterinary field station is described in detail and an account given of the authors' experience with the technique in nearly 200 cases. It is concluded that the approach to the abdominal cavity is easy, that the testis itself is generally readily located and removed and that controlled repair of the incision is possible. Serious post-operative complications are rare and the danger of post-operative prolapse of bowel eliminated.", "contents": "Suprapubic paramedian laparotomy for equine abdominal cryptorchidism. The history of techniques for abdominal equine cryptorchidectomy is briefly reviewed. The technique of suprapubic paramedian laparotomy as used since 1955 at the University of Liverpool veterinary field station is described in detail and an account given of the authors' experience with the technique in nearly 200 cases. It is concluded that the approach to the abdominal cavity is easy, that the testis itself is generally readily located and removed and that controlled repair of the incision is possible. Serious post-operative complications are rare and the danger of post-operative prolapse of bowel eliminated."}
{"id": "PMID:3015", "title": "[Bacteriological and physicochemical studies of the meat from poultry with acute Marek's disease].", "content": "Studied were bacteriologically a total of 114 birds affected with acute Marek's disease (40 broilers, 44 growing layers, and 30 adult layers) as well as 100 healthy control birds of the same three categories. A chemical analysis was performed of the red and white meat of 20 of the diseased pullets and 20 of the diseased adult layers as well as of 34 of the affected broilers. The investigation included the same numbers of the control birds. Extractions of the sampled meat were studied in terms of catalase number, pH value, and peroxydase activity. It was found that enterobacteria in the viscera of the diseased birds were three to nine times more frequently encountered than in the same organs of the controls. In two cases Salmonella bacteria were also isolated from the affected chickens. In three cases there were enterobacteria in the red musculature of these birds. The meat of the diseased birds had higher water content, higher catalase number and pH value, with lower contents of proteins, fats, and mineral matter. The only exception was the red meat of these birds which had higher content of crude protein as compared with the red meat of the normal birds.", "contents": "[Bacteriological and physicochemical studies of the meat from poultry with acute Marek's disease]. Studied were bacteriologically a total of 114 birds affected with acute Marek's disease (40 broilers, 44 growing layers, and 30 adult layers) as well as 100 healthy control birds of the same three categories. A chemical analysis was performed of the red and white meat of 20 of the diseased pullets and 20 of the diseased adult layers as well as of 34 of the affected broilers. The investigation included the same numbers of the control birds. Extractions of the sampled meat were studied in terms of catalase number, pH value, and peroxydase activity. It was found that enterobacteria in the viscera of the diseased birds were three to nine times more frequently encountered than in the same organs of the controls. In two cases Salmonella bacteria were also isolated from the affected chickens. In three cases there were enterobacteria in the red musculature of these birds. The meat of the diseased birds had higher water content, higher catalase number and pH value, with lower contents of proteins, fats, and mineral matter. The only exception was the red meat of these birds which had higher content of crude protein as compared with the red meat of the normal birds."}
{"id": "PMID:3020", "title": "[The function of shuttle systems of liver extramitochondrial hydrogen transport in experimental atherosclerosis].", "content": "An enzymatic activity of shuttle systems for reduction equivalents transport (malate-aspartate, glycerophosphate, lactate, glutamate and beta-hydroxybutyrate dehydrogenase) was studied spectrophotometrically in liver tissue of intact rabbits and animals with experimental atherosclerosis. Content of malate, oxaloacetate, glutamate, alpha-ketoglutarate, alpha-glycerophosphate, dihydroacetone phosphate, lactate, pyruvate, beta-hydroxybutyrate and acetoacetate were studied. In experimental atherosclerosis coordinated functioning of the enzymes, which participate in the utilization of the cytoplasmic NAD-H2 and the alteration in the ratio of reduced and oxidized metabolites in the systems, were found to be impaired.", "contents": "[The function of shuttle systems of liver extramitochondrial hydrogen transport in experimental atherosclerosis]. An enzymatic activity of shuttle systems for reduction equivalents transport (malate-aspartate, glycerophosphate, lactate, glutamate and beta-hydroxybutyrate dehydrogenase) was studied spectrophotometrically in liver tissue of intact rabbits and animals with experimental atherosclerosis. Content of malate, oxaloacetate, glutamate, alpha-ketoglutarate, alpha-glycerophosphate, dihydroacetone phosphate, lactate, pyruvate, beta-hydroxybutyrate and acetoacetate were studied. In experimental atherosclerosis coordinated functioning of the enzymes, which participate in the utilization of the cytoplasmic NAD-H2 and the alteration in the ratio of reduced and oxidized metabolites in the systems, were found to be impaired."}
{"id": "PMID:3022", "title": "[The specificity of galactokinase induction in rat liver tissue under the effect of galactose].", "content": "In liver tissue of rats, a conventional laboratory food of which was substituted for galactose-rich food, the galactokinase activity was increased, but the glucokinase was not affected. In the rats kept on a glucose-rich food the glucokinase (but not the galactokinase) was activated. Hydrocortisone injection induced an increase in tyrosine aminotransferase, but the galactokinase activity was not altered. The data obtained suggest that in rat liver tissue the galactokinase was specifically induced under the effect of galactose. Except for the liver tissue, galactose induced galactokinase in eye crystalline lens; the enzyme activity was not altered in spleen and kidney.", "contents": "[The specificity of galactokinase induction in rat liver tissue under the effect of galactose]. In liver tissue of rats, a conventional laboratory food of which was substituted for galactose-rich food, the galactokinase activity was increased, but the glucokinase was not affected. In the rats kept on a glucose-rich food the glucokinase (but not the galactokinase) was activated. Hydrocortisone injection induced an increase in tyrosine aminotransferase, but the galactokinase activity was not altered. The data obtained suggest that in rat liver tissue the galactokinase was specifically induced under the effect of galactose. Except for the liver tissue, galactose induced galactokinase in eye crystalline lens; the enzyme activity was not altered in spleen and kidney."}
{"id": "PMID:3019", "title": "[Age-related properties of inductive synthesis of glucose-6-phosphatase, fructose-1,6-diphosphatase, tyrosine aminotransferase and tryptophan pyrrolase in hypothalamus stimulation].", "content": "In aged rats electrostimulation of hypothalamus caused less distinct induction of the enzymes in liver tissue, kidney and spleen as compared with the adult animals. The activation of the total RNA synthesis (actinomycin D and olivomycin) eliminated the alterations in the enzymatic activities, caused by the stimulation of hypothalamus. Effect of adrenalectomy and administration of ACTH suggested that the influence of the hypothalamus stimulation on induction of the enzymes studied was realized through the system hypophysis -- adrenal cortex. In the aged animals activation of adrenal cortex was less distinct when the stimulation of hypothalamus was carried out. The alterations in hypothalamic regulation of the enzyme induction could be an important mechanism in regulation of adaptive reactions in aged organisms.", "contents": "[Age-related properties of inductive synthesis of glucose-6-phosphatase, fructose-1,6-diphosphatase, tyrosine aminotransferase and tryptophan pyrrolase in hypothalamus stimulation]. In aged rats electrostimulation of hypothalamus caused less distinct induction of the enzymes in liver tissue, kidney and spleen as compared with the adult animals. The activation of the total RNA synthesis (actinomycin D and olivomycin) eliminated the alterations in the enzymatic activities, caused by the stimulation of hypothalamus. Effect of adrenalectomy and administration of ACTH suggested that the influence of the hypothalamus stimulation on induction of the enzymes studied was realized through the system hypophysis -- adrenal cortex. In the aged animals activation of adrenal cortex was less distinct when the stimulation of hypothalamus was carried out. The alterations in hypothalamic regulation of the enzyme induction could be an important mechanism in regulation of adaptive reactions in aged organisms."}
{"id": "PMID:3024", "title": "[Determination of the transferase activity of L-asparaginase].", "content": "A method for determination of the transferase activity of 1-asparaginase in presence of hydroxylamine is developed. The optimally determined quantity of the enzyme was from 0.7 to 20 i. u. The conditions optimal for the enzymatic reaction and for quantitative estimation of 1-aspartyl-beta-hydroxamic acid were studied. The transferase and hydrolase activities of 1-asparaginase from E. coli were compared. The enzyme catalyzed at equal rates hydrolysis and hydroxylaminolysis of 1-asparagine.", "contents": "[Determination of the transferase activity of L-asparaginase]. A method for determination of the transferase activity of 1-asparaginase in presence of hydroxylamine is developed. The optimally determined quantity of the enzyme was from 0.7 to 20 i. u. The conditions optimal for the enzymatic reaction and for quantitative estimation of 1-aspartyl-beta-hydroxamic acid were studied. The transferase and hydrolase activities of 1-asparaginase from E. coli were compared. The enzyme catalyzed at equal rates hydrolysis and hydroxylaminolysis of 1-asparagine."}
{"id": "PMID:3021", "title": "[The effect of lipids from typhoid endotoxin on the activity of some liver enzymes].", "content": "Sublethal doses of typhoid endotoxin distinctly increased the activities of glutamate dehydrogenase and histidine ammonium lyase in liver tissue of mice within 3 hrs and the tyrosine transaminase activity within 6 hrs after a single intraperitoneal administration. Within 24 hrs normalzation of these enzyme activities and a decrease in the urocaninase activity were observed in liver tissue. Lipid A, obtained from the endotoxin, activated glutamate dehydrogenase and histidine ammonium lyase, inhibited urocaninase but did not affect the tyrosine transaminase activity. Lipid B, isolated by a non-hydrolytic method, showed even wore distinct capacity to activate glutamate dehydrogenase and histidine ammonium lyase, but did not alter the activities of tyrosine transaminase and urocaninase in liver tissue.", "contents": "[The effect of lipids from typhoid endotoxin on the activity of some liver enzymes]. Sublethal doses of typhoid endotoxin distinctly increased the activities of glutamate dehydrogenase and histidine ammonium lyase in liver tissue of mice within 3 hrs and the tyrosine transaminase activity within 6 hrs after a single intraperitoneal administration. Within 24 hrs normalzation of these enzyme activities and a decrease in the urocaninase activity were observed in liver tissue. Lipid A, obtained from the endotoxin, activated glutamate dehydrogenase and histidine ammonium lyase, inhibited urocaninase but did not affect the tyrosine transaminase activity. Lipid B, isolated by a non-hydrolytic method, showed even wore distinct capacity to activate glutamate dehydrogenase and histidine ammonium lyase, but did not alter the activities of tyrosine transaminase and urocaninase in liver tissue."}
{"id": "PMID:3027", "title": "[Purification and properties of myeloperoxidase from mice leukocytes].", "content": "Myeloperoxidase from leucocytes of peritoneal exudate was isolated by chromatography on DEAE-Sephadex, CM-cellulose and gel filtration on Sephadex G-75. The preparation obtained was homogenous as shown by repeated gel filtration and ultracentrifugation. The enzyme was purified 302-fold, with 16% yield. The sedimentation constant was equal to 4.05 S. Molecular weight of the enzyme, determined by gel filtration on Sephadex G-100, constituted 135,000 daltons. Myeloperoxidase had two pH optima of activity--at pH 4.6 and at pH 7.6. Km for o-dianizidine was equal to 4.0-10(-3)M and for hydrogen peroxide--to 1.65-10(-4)M. Myeloperoxidase of mice leucocytes differed from the enzymes of leucocytes from other animal species in its distinctly lower sedimentation constant and thermolability.", "contents": "[Purification and properties of myeloperoxidase from mice leukocytes]. Myeloperoxidase from leucocytes of peritoneal exudate was isolated by chromatography on DEAE-Sephadex, CM-cellulose and gel filtration on Sephadex G-75. The preparation obtained was homogenous as shown by repeated gel filtration and ultracentrifugation. The enzyme was purified 302-fold, with 16% yield. The sedimentation constant was equal to 4.05 S. Molecular weight of the enzyme, determined by gel filtration on Sephadex G-100, constituted 135,000 daltons. Myeloperoxidase had two pH optima of activity--at pH 4.6 and at pH 7.6. Km for o-dianizidine was equal to 4.0-10(-3)M and for hydrogen peroxide--to 1.65-10(-4)M. Myeloperoxidase of mice leucocytes differed from the enzymes of leucocytes from other animal species in its distinctly lower sedimentation constant and thermolability."}
{"id": "PMID:3023", "title": "[Changes in oxidative systems of liver microsomes in rats following a single administration of phenobarbital and morphine].", "content": "During the first three hours after a single administration of phenobarbital or morphine into rats a marked increase was observed in the activity and content of the respiratory chain components responsible for the oxidation of NAD-H2 and NADP-H2 in liver microsomes. This activation of oxidative enzymes correlated with the disappearance of hypnotic and analgetic effects of the narcotics. The phase following the normalization of oxydative systems was characterized by the increase of microsomal enzymes level. This is related to their specific induction only by phenobarbital.", "contents": "[Changes in oxidative systems of liver microsomes in rats following a single administration of phenobarbital and morphine]. During the first three hours after a single administration of phenobarbital or morphine into rats a marked increase was observed in the activity and content of the respiratory chain components responsible for the oxidation of NAD-H2 and NADP-H2 in liver microsomes. This activation of oxidative enzymes correlated with the disappearance of hypnotic and analgetic effects of the narcotics. The phase following the normalization of oxydative systems was characterized by the increase of microsomal enzymes level. This is related to their specific induction only by phenobarbital."}
{"id": "PMID:3025", "title": "[Isolation and properties of 2 kallikreins from human saliva].", "content": "Two kallikreins (K-I and K-II) were purified from mixed, parotid and submandibular human saliva. The kallikreins were separated by chromatography on CM-cellulose. The pH optima of activity were at pH 9.3 and pH 9.6-9.8; Km for BAEE was 1.10-3M and 4.10-3M, respectively. The esterase activity of K-I and K-II was inhibited by trasylol-like inhibitors, while the plant and synthetic inhibitors of trypsin were uneffective. In dog, rabbit and rat the hypotensive effect of K-II and its action upon the permeability of rabbit skin was 4-5 fold higher than the effects of K-I. Ki and K-II did not alter the arterial blood pressure in guinea pig.", "contents": "[Isolation and properties of 2 kallikreins from human saliva]. Two kallikreins (K-I and K-II) were purified from mixed, parotid and submandibular human saliva. The kallikreins were separated by chromatography on CM-cellulose. The pH optima of activity were at pH 9.3 and pH 9.6-9.8; Km for BAEE was 1.10-3M and 4.10-3M, respectively. The esterase activity of K-I and K-II was inhibited by trasylol-like inhibitors, while the plant and synthetic inhibitors of trypsin were uneffective. In dog, rabbit and rat the hypotensive effect of K-II and its action upon the permeability of rabbit skin was 4-5 fold higher than the effects of K-I. Ki and K-II did not alter the arterial blood pressure in guinea pig."}
{"id": "PMID:3026", "title": "[The correlation between activity of enzymes participating in the formation and utilization of acetyl CoA in rabbit heart mitochondria in myocarditis and normal state].", "content": "Activities in rabbit heart mitochondria of acetoacetyl-CoA-thyolase, pyruvate dehydrogenase, acetyl CoA-synthetase, citrate synthase and acetyl carnitine transferase were compared. These enzymes participate in formation and utilization of acetyl-CoA. The acetoacetyl-CoA-thyolase and acetyl CoA-synthetase were shown to possess the more distinct capacity in vitro to form acetyl CoA. The co-enzyme was most efficiently utilized under these experimental conditions by the citrate synthase. The enzymes studied were localized within the mitochondria fraction in both the subfractions of soluble and membrane-bound proteins. In myocarditis a distinct decrease in activities of the acetoacetyl-CoA-thyolase and citrate synthase was observed.", "contents": "[The correlation between activity of enzymes participating in the formation and utilization of acetyl CoA in rabbit heart mitochondria in myocarditis and normal state]. Activities in rabbit heart mitochondria of acetoacetyl-CoA-thyolase, pyruvate dehydrogenase, acetyl CoA-synthetase, citrate synthase and acetyl carnitine transferase were compared. These enzymes participate in formation and utilization of acetyl-CoA. The acetoacetyl-CoA-thyolase and acetyl CoA-synthetase were shown to possess the more distinct capacity in vitro to form acetyl CoA. The co-enzyme was most efficiently utilized under these experimental conditions by the citrate synthase. The enzymes studied were localized within the mitochondria fraction in both the subfractions of soluble and membrane-bound proteins. In myocarditis a distinct decrease in activities of the acetoacetyl-CoA-thyolase and citrate synthase was observed."}
{"id": "PMID:3038", "title": "[New values for the molar extinction coefficients of NADH and NADPH for the use in routine laboratories (author's transl)].", "content": "Extensive re-investigations with regard to the molar extinction coefficients of NADH and NADPH proved that in future, calculations in routine work can be performed with the following much more accurate epsilon-values: 6.15 x 10(3) 1 x mol-1 x cm-1 at Hg 334 nm (NADH and NADPH), 6.3 X 10(3) 1 X mol-1 x cm-1 at 340 nm (NADH and NADPH), 3.4 X 10(3) 1 X mol-1 X Cm-1 (NADH) and 3.5 x 10(3) 1 x mol-1 x cm-1 (NADPH) at Hg 365 nm, respectively. The safest measurement is performed at Hg 334 nm, because here epsilon is identical for both coenzymes and deviations of the epsilon-value caused by temperature, pH and ionic strength are less than 0.5%.", "contents": "[New values for the molar extinction coefficients of NADH and NADPH for the use in routine laboratories (author's transl)]. Extensive re-investigations with regard to the molar extinction coefficients of NADH and NADPH proved that in future, calculations in routine work can be performed with the following much more accurate epsilon-values: 6.15 x 10(3) 1 x mol-1 x cm-1 at Hg 334 nm (NADH and NADPH), 6.3 X 10(3) 1 X mol-1 x cm-1 at 340 nm (NADH and NADPH), 3.4 X 10(3) 1 X mol-1 X Cm-1 (NADH) and 3.5 x 10(3) 1 x mol-1 x cm-1 (NADPH) at Hg 365 nm, respectively. The safest measurement is performed at Hg 334 nm, because here epsilon is identical for both coenzymes and deviations of the epsilon-value caused by temperature, pH and ionic strength are less than 0.5%."}
{"id": "PMID:3039", "title": "[The metabolism of delta4-3-oxosteroids in rat liver].", "content": "The enzymatic reactions are described by which delta4-3-oxosteroids, specially testosterone, are inactivated in rat liver. The delta4-3-oxosteroid-5 alpha-reductase in liver microsomes was studied intensively and it was found that it is an enzyme system. The 5 alpha-reduction of testosterone with NADPH or with NADH depends upon different enzymes or enzyme systems.", "contents": "[The metabolism of delta4-3-oxosteroids in rat liver]. The enzymatic reactions are described by which delta4-3-oxosteroids, specially testosterone, are inactivated in rat liver. The delta4-3-oxosteroid-5 alpha-reductase in liver microsomes was studied intensively and it was found that it is an enzyme system. The 5 alpha-reduction of testosterone with NADPH or with NADH depends upon different enzymes or enzyme systems."}
{"id": "PMID:3040", "title": "[An improved trihydroxyindole method for the determination of urinary catecholamines].", "content": "Commercially available columns for ion exchange chromatography were used for the separation of catecholamines in urine. The estimation of catecholamines was performed fluorimetrically by a new trihydroxyindole method. The fluorescence of adrenaline or noradrenaline was enhanced, in comparison with other methods, by the combined application of boric acid, copper-ions, mercaptoethanol and final reacidification. The fluorophores are stable: The loss of fluorescence of adrenolutin amounted to 22% during 180 minutes, and there was no loss of noradrenolutin. For the differentiation of amines, adrenaline was oxidized at pH 2.85 and noradrenaline at pH 7. Precision, accuracy, sensitivity and specifity fulfilled the criteria of analysis. The normal values, determined in a collective of 17 healthy persons, were adrenaline (x +/- s) 44.8 +/- 16.9 nmol/24 h and noradrenaline (x +/- s) 224.0 +/- 68.0 nmol/24h. The simultaneous application of alpha-methyldopa (2 g/day) in 13 patients with primary hypertension did not disturb the fluorimetric estimation of catecholamines.", "contents": "[An improved trihydroxyindole method for the determination of urinary catecholamines]. Commercially available columns for ion exchange chromatography were used for the separation of catecholamines in urine. The estimation of catecholamines was performed fluorimetrically by a new trihydroxyindole method. The fluorescence of adrenaline or noradrenaline was enhanced, in comparison with other methods, by the combined application of boric acid, copper-ions, mercaptoethanol and final reacidification. The fluorophores are stable: The loss of fluorescence of adrenolutin amounted to 22% during 180 minutes, and there was no loss of noradrenolutin. For the differentiation of amines, adrenaline was oxidized at pH 2.85 and noradrenaline at pH 7. Precision, accuracy, sensitivity and specifity fulfilled the criteria of analysis. The normal values, determined in a collective of 17 healthy persons, were adrenaline (x +/- s) 44.8 +/- 16.9 nmol/24 h and noradrenaline (x +/- s) 224.0 +/- 68.0 nmol/24h. The simultaneous application of alpha-methyldopa (2 g/day) in 13 patients with primary hypertension did not disturb the fluorimetric estimation of catecholamines."}
{"id": "PMID:3045", "title": "[Biochemical investigations of cancer cachexia. II. Depletion of glycogenolysis and stimulation of gluconeogenesis in Walker carcinoma 256 bearing rats (author's transl)].", "content": "150-200 g heavy, Walker-carcinoma bearing, male Sprague-Dawley-rats showed rapid, tumour weight dependent, loss of liver glycogen until complete depletion in tumour groups heavier than 40 g/animal. Simultaneously the glycogen mobilization after massive glucagon stimulation, was successivly diminished and finally abolished in different groups with increasing tumor weight. Concomitantly the spontaneous and stimulated activity of liver phosphorylase a was found markedly reduced in advanced tumour cachexia, the extent of stimulation of liver phosphorylase a activity by intracardial injections of epinephrine not being altered. Tumour induced inhibition of glycogen mobilization thus appears to have been excluded. To account for the relative late pronounced hypoglycemia in peripherial rat blood in face of the early loss of liver glycogen, accelerated gluconeogenesis has been postulated. In accord with this spontaneous rise in liver tyrosine amino transferase was found in tumour bearing rats along with a doubled maximal stimulation value after medrol injection as compared to control groups. This behavior could not be shown for liver alanine aminotransferase and liver fructose 1,6-di-phosphatase. The former showed no differences between control and tumour groups neither of spontaneous nor of stimulated activity. The latter showed only a very reluctant rise after massive stimulation by triamcinolone for 3 days in the control groups, the tumour bearing groups showing no deviation from spontaneous control values.", "contents": "[Biochemical investigations of cancer cachexia. II. Depletion of glycogenolysis and stimulation of gluconeogenesis in Walker carcinoma 256 bearing rats (author's transl)]. 150-200 g heavy, Walker-carcinoma bearing, male Sprague-Dawley-rats showed rapid, tumour weight dependent, loss of liver glycogen until complete depletion in tumour groups heavier than 40 g/animal. Simultaneously the glycogen mobilization after massive glucagon stimulation, was successivly diminished and finally abolished in different groups with increasing tumor weight. Concomitantly the spontaneous and stimulated activity of liver phosphorylase a was found markedly reduced in advanced tumour cachexia, the extent of stimulation of liver phosphorylase a activity by intracardial injections of epinephrine not being altered. Tumour induced inhibition of glycogen mobilization thus appears to have been excluded. To account for the relative late pronounced hypoglycemia in peripherial rat blood in face of the early loss of liver glycogen, accelerated gluconeogenesis has been postulated. In accord with this spontaneous rise in liver tyrosine amino transferase was found in tumour bearing rats along with a doubled maximal stimulation value after medrol injection as compared to control groups. This behavior could not be shown for liver alanine aminotransferase and liver fructose 1,6-di-phosphatase. The former showed no differences between control and tumour groups neither of spontaneous nor of stimulated activity. The latter showed only a very reluctant rise after massive stimulation by triamcinolone for 3 days in the control groups, the tumour bearing groups showing no deviation from spontaneous control values."}
{"id": "PMID:3046", "title": "Oxidative decarboxylation of para-hydroxybenzoic acids by peroxidases under in vivo and in vitro conditions.", "content": "Oxidative decarbyxylation of p-hydroxybenzoic acids in plant cell suspension cultures is catalyzed by peroxidases. This reaction has been characterized in vivo and in vitro. Decarboxylation of substituted benzoic acids yields monomeric, dimeric and oligomeric benzoquinones. All peroxidases obtained from soybean (Glycine max) cell suspension cultures by gel electrophoresis are equally capable to decarboxylate p-hydroxygenzoic acids as indicated by their rather low differences in specific activity for various benzoic acids.", "contents": "Oxidative decarboxylation of para-hydroxybenzoic acids by peroxidases under in vivo and in vitro conditions. Oxidative decarbyxylation of p-hydroxybenzoic acids in plant cell suspension cultures is catalyzed by peroxidases. This reaction has been characterized in vivo and in vitro. Decarboxylation of substituted benzoic acids yields monomeric, dimeric and oligomeric benzoquinones. All peroxidases obtained from soybean (Glycine max) cell suspension cultures by gel electrophoresis are equally capable to decarboxylate p-hydroxygenzoic acids as indicated by their rather low differences in specific activity for various benzoic acids."}
{"id": "PMID:3047", "title": "The regulation of glucose-6-phosphate dehydrogenase in chloroplasts.", "content": "Glucose-6-phosphate dehydrogenase from intact pea chloroplasts is partially membrane bound and inactivated upon illumination. The inhibitory effect of light can be abolished by addition of methylviologen. Kinetic experiments with glucose-6-phosphate dehydrogenase reveal that, in the dark, the enzyme activity is strongly inhibited by the accumulation of NADPH. The inhibition of NADPH can be reversed by the addition of excess NADP+. The non-Michaelis-Menten-type kinetics suggest that the enzyme is stringently regulated by the ratio of NADPH to NADP+ plus NADPH, i.e., the \"reduction charge\". These observations seem to indicate that in the light the inhibition of glucose-6-phosphate dehydrogenase is due to a high reduction charge, whereas in the dark the enzyme is controlled by the metabolic demand for reducing equivalents.", "contents": "The regulation of glucose-6-phosphate dehydrogenase in chloroplasts. Glucose-6-phosphate dehydrogenase from intact pea chloroplasts is partially membrane bound and inactivated upon illumination. The inhibitory effect of light can be abolished by addition of methylviologen. Kinetic experiments with glucose-6-phosphate dehydrogenase reveal that, in the dark, the enzyme activity is strongly inhibited by the accumulation of NADPH. The inhibition of NADPH can be reversed by the addition of excess NADP+. The non-Michaelis-Menten-type kinetics suggest that the enzyme is stringently regulated by the ratio of NADPH to NADP+ plus NADPH, i.e., the \"reduction charge\". These observations seem to indicate that in the light the inhibition of glucose-6-phosphate dehydrogenase is due to a high reduction charge, whereas in the dark the enzyme is controlled by the metabolic demand for reducing equivalents."}
{"id": "PMID:3050", "title": "Characterization of different deoxyribonucleases in human lymphocytes.", "content": "Four groups of deoxyribonuclease activities from human lymphocytes have been characterized by deoxyribonuclease assay in DNA-containing polyacrylamide gels following their separation by disc-electrophoresis. All activities hydrolyse DNA endonucleolytically. One neutral deoxyribonuclease found in the cytoplasmic fraction prefers native or UV-irradiated DNA over denatured DNA as substrate and is a 5'-monoester former. Two groups of acid deoxyribonuclease activities are detectable in the nuclear fraction. Both are 3'-monoester formers. One is as well active with denatured DNA as with native DNA, the other one shows the same activity with native and UV-irradiated DNA but lower activity with denatured DNA. An alkaline deoxyribonuclease activity, also localized in the nucleus, is a 5'-monoester former, and prefers denatured or UV-irradiated DNA as substrate.", "contents": "Characterization of different deoxyribonucleases in human lymphocytes. Four groups of deoxyribonuclease activities from human lymphocytes have been characterized by deoxyribonuclease assay in DNA-containing polyacrylamide gels following their separation by disc-electrophoresis. All activities hydrolyse DNA endonucleolytically. One neutral deoxyribonuclease found in the cytoplasmic fraction prefers native or UV-irradiated DNA over denatured DNA as substrate and is a 5'-monoester former. Two groups of acid deoxyribonuclease activities are detectable in the nuclear fraction. Both are 3'-monoester formers. One is as well active with denatured DNA as with native DNA, the other one shows the same activity with native and UV-irradiated DNA but lower activity with denatured DNA. An alkaline deoxyribonuclease activity, also localized in the nucleus, is a 5'-monoester former, and prefers denatured or UV-irradiated DNA as substrate."}
{"id": "PMID:3051", "title": "Studies on fragments of rod outer segments from bovine retinas.", "content": "Monolayers of fragments of our rod segments were formed at an air-water interface. The area of these particles was measured as a function of the pH of the aqueous phase. A maximum area was measured at pH 6.5. The film was characterised by measuring the decrease in surface pressure, after compression, and the half time required to reach constant pressure. At a pH between 6 and 7 the decrease in surface pressure was a minimum. Irradiation of films of fragments resulted in a decrease in surface potential of between 30 and 40 mV. The largest decrease occured at a pH between 6 and 6.5. A small decrease in surface pressure was also observed upon irradiation. Mixed films of fragments and phosphatidyl ethanolamine were examined. Irradiation of the mixed film resulted in a 70 mV decrease in surface potential.", "contents": "Studies on fragments of rod outer segments from bovine retinas. Monolayers of fragments of our rod segments were formed at an air-water interface. The area of these particles was measured as a function of the pH of the aqueous phase. A maximum area was measured at pH 6.5. The film was characterised by measuring the decrease in surface pressure, after compression, and the half time required to reach constant pressure. At a pH between 6 and 7 the decrease in surface pressure was a minimum. Irradiation of films of fragments resulted in a decrease in surface potential of between 30 and 40 mV. The largest decrease occured at a pH between 6 and 6.5. A small decrease in surface pressure was also observed upon irradiation. Mixed films of fragments and phosphatidyl ethanolamine were examined. Irradiation of the mixed film resulted in a 70 mV decrease in surface potential."}
{"id": "PMID:3052", "title": "The ionization and optical properties of oxoformycin.", "content": "Details are given of the ultraviolet, optical rotatory dispersion and fluorescence spectra of oxoformycin. The pK of formation of the monoanion is 8.6, at 25 degrees C. As formycin B has the same pK value, the ionization of both compounds is ascribed to dissociation of a proton from N-1. Both the neutral and monoanionic forms of oxoformycin are strongly fluorescent.", "contents": "The ionization and optical properties of oxoformycin. Details are given of the ultraviolet, optical rotatory dispersion and fluorescence spectra of oxoformycin. The pK of formation of the monoanion is 8.6, at 25 degrees C. As formycin B has the same pK value, the ionization of both compounds is ascribed to dissociation of a proton from N-1. Both the neutral and monoanionic forms of oxoformycin are strongly fluorescent."}
{"id": "PMID:3048", "title": "Antagonistic relationships between electron transport and P700 in chloroplasts and intact algae.", "content": "The effects of divalent salts and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) upon nicotinamide adenine dinucleotide phosphate (NADP) reduction and P700 in isolated chloroplasts are described and compared with the influence of DCMU on oxygen evolution and P700 in intact cells. Most experiments were carried out with a steady-state relaxation spectrometer. A kinetic mechanism for the estimation of P700 fluxes is proposed and experimentally tested. Good agreement between theory and experiment was found. Concurrent measurements of P700 and NADP reduction revealed two antagonisms: addition of divalent cations caused an increase in the yield of NADP reduction and a decrease in the yield of P700. Conversely, in the presence of Mg2+ low concentrations of DCMU decreased the yield of NADP reduction and increased the yield of P700. Aging of the chloroplasts at 30 degrees C exerted a similar effect. With far-red actinic light, Mg2+ stimulated the yield of NADP reduction without affecting the flux. Also, in the absence of Mg2+, DCMU inhibited both reactions although P700 required a higher herbicide concentration for fractional inhibition than NADP reduction. In the presence of Mg2+, chloroplasts resembled intact algae in which a high rate of oxygen evolution was accompanied by little P700 turn-over. Titration with DCMU decreased the rate of photosynthesis and increased P700 flux. On the whole, the data suggest that P700 relaxing in 20 msec is not directly involved in linear electron transport.", "contents": "Antagonistic relationships between electron transport and P700 in chloroplasts and intact algae. The effects of divalent salts and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) upon nicotinamide adenine dinucleotide phosphate (NADP) reduction and P700 in isolated chloroplasts are described and compared with the influence of DCMU on oxygen evolution and P700 in intact cells. Most experiments were carried out with a steady-state relaxation spectrometer. A kinetic mechanism for the estimation of P700 fluxes is proposed and experimentally tested. Good agreement between theory and experiment was found. Concurrent measurements of P700 and NADP reduction revealed two antagonisms: addition of divalent cations caused an increase in the yield of NADP reduction and a decrease in the yield of P700. Conversely, in the presence of Mg2+ low concentrations of DCMU decreased the yield of NADP reduction and increased the yield of P700. Aging of the chloroplasts at 30 degrees C exerted a similar effect. With far-red actinic light, Mg2+ stimulated the yield of NADP reduction without affecting the flux. Also, in the absence of Mg2+, DCMU inhibited both reactions although P700 required a higher herbicide concentration for fractional inhibition than NADP reduction. In the presence of Mg2+, chloroplasts resembled intact algae in which a high rate of oxygen evolution was accompanied by little P700 turn-over. Titration with DCMU decreased the rate of photosynthesis and increased P700 flux. On the whole, the data suggest that P700 relaxing in 20 msec is not directly involved in linear electron transport."}
{"id": "PMID:3049", "title": "Energy-linked pyridine nucleotide transhydrogenase activity in photosynthetically grown Rhodopseudomonas palustris.", "content": "Rhodopseudomonas palustris (ATCC 17001) develops energy-dependent NADP+ transhydrogenase activity while growing photosynthetically on thiosulfate, formate, or acetate as the electron donors. The enzymatic activity is present in the supernatant fraction S-144 000. -- As reported, this fraction contains small membrane fragments but no closed vesicles and was shown to drive energy-dependent reversed electron flow as well as an aerobic respiratory electron transport. The energy-dependent transhydrogenase reaction in this fraction can be driven either by ATP, ADP, or inorganic pyrophosphate, but also by acetyl phosphate or acetyl-coenzyme A in the presence of orthophosphate. -- Arsenate acts as an inhibitor and decreases preferentially the acetyl-coenzyme A-dependent and the acetyl phosphate-driven reaction; whereas, oligomycin inhibits preferentially the ATP- and the acetyl phosphate-dependent reactions. -- Acetate kinase and a phosphotransacetylase are operative in S-144 000.", "contents": "Energy-linked pyridine nucleotide transhydrogenase activity in photosynthetically grown Rhodopseudomonas palustris. Rhodopseudomonas palustris (ATCC 17001) develops energy-dependent NADP+ transhydrogenase activity while growing photosynthetically on thiosulfate, formate, or acetate as the electron donors. The enzymatic activity is present in the supernatant fraction S-144 000. -- As reported, this fraction contains small membrane fragments but no closed vesicles and was shown to drive energy-dependent reversed electron flow as well as an aerobic respiratory electron transport. The energy-dependent transhydrogenase reaction in this fraction can be driven either by ATP, ADP, or inorganic pyrophosphate, but also by acetyl phosphate or acetyl-coenzyme A in the presence of orthophosphate. -- Arsenate acts as an inhibitor and decreases preferentially the acetyl-coenzyme A-dependent and the acetyl phosphate-driven reaction; whereas, oligomycin inhibits preferentially the ATP- and the acetyl phosphate-dependent reactions. -- Acetate kinase and a phosphotransacetylase are operative in S-144 000."}
{"id": "PMID:3073", "title": "[Findings of subpartal monitoring, status of the newborn infant and evaluation of cardiotocographic findings].", "content": "The parameters of the intrapartal fetal CTG and the actual pH are related to each other and to the Apgar score of the newborn. The interpretation was carried out by means of groups of 300 to 600 cases. The actual fetal pH has the most compact relation to the Apgar score of the newborn (C equals 0,31). But also this contingence is unsatisfactory. At fetal acidosis most of the Apgar scores are pathological, in that manner the pH is the most important test for indication of operative delivery. The rare CTG pattern as dip II and variable decelerations combined with tachycardia of bradycardia, the bradycardia with 80 bpm or less, are likewise indications of urgent delivery.", "contents": "[Findings of subpartal monitoring, status of the newborn infant and evaluation of cardiotocographic findings]. The parameters of the intrapartal fetal CTG and the actual pH are related to each other and to the Apgar score of the newborn. The interpretation was carried out by means of groups of 300 to 600 cases. The actual fetal pH has the most compact relation to the Apgar score of the newborn (C equals 0,31). But also this contingence is unsatisfactory. At fetal acidosis most of the Apgar scores are pathological, in that manner the pH is the most important test for indication of operative delivery. The rare CTG pattern as dip II and variable decelerations combined with tachycardia of bradycardia, the bradycardia with 80 bpm or less, are likewise indications of urgent delivery."}
{"id": "PMID:3074", "title": "[Influence of low molecular dextran on the acid-base balance in mother and fetus].", "content": "9 normal pregnant women in the active phase of labor were treated with 500 ml low molecular dextrane with a pH of 4,5 under standardised external conditions. Before and after this infusion simultaneous estimations of the maternal and fetal acid-base status were made. There was neither a maternal nor a fetal acidosis.", "contents": "[Influence of low molecular dextran on the acid-base balance in mother and fetus]. 9 normal pregnant women in the active phase of labor were treated with 500 ml low molecular dextrane with a pH of 4,5 under standardised external conditions. Before and after this infusion simultaneous estimations of the maternal and fetal acid-base status were made. There was neither a maternal nor a fetal acidosis."}
{"id": "PMID:3077", "title": "[Acetyl-CoA-synthetase activity of pigmented staphylococci].", "content": "In 19 strains of staphylococci a study was made of the activity of acetyl-CoA-synthetase reaction. All the strains possessed an active enzymatic system transforming the acetate into an active form. The activity of acetyl-CoA-synthetase proved to be much greater in the pigmented staphyloccus strains than in the nonpigmented ones. It is supposed that there existed an association between the acetyl-CoA-synthetase and the biogenesis of carotinoid pigments in Staph. aureus.", "contents": "[Acetyl-CoA-synthetase activity of pigmented staphylococci]. In 19 strains of staphylococci a study was made of the activity of acetyl-CoA-synthetase reaction. All the strains possessed an active enzymatic system transforming the acetate into an active form. The activity of acetyl-CoA-synthetase proved to be much greater in the pigmented staphyloccus strains than in the nonpigmented ones. It is supposed that there existed an association between the acetyl-CoA-synthetase and the biogenesis of carotinoid pigments in Staph. aureus."}
{"id": "PMID:3075", "title": "[Acetylcholinesterase from the electric organ of the ray Torpedo marmorata].", "content": "Studies have been made on substrate specificity of acetylcholinesterase (AChE;EC 3-1-1-7) from the electric organ of the ray T. marmorata with respect of choline and thiocholine esters, as well as on the effect of pH, salts and organophosphorus inhibitors (OPI) on the activity of the enzyme. Acetylcholine (ACh), propionycholine (PrCh) acetyl-beta-methylcholine (MeCh), acetylthiocholine ((ATCh) and propionylthiocholine (PrTCh) were hydrolyzed by the enzyme studied at the following relative rates-100: 28.8: 18.3: 87.2: 18.9 correspondingly. In all the cases, inhibition of the enzyme by high concentrations of the substrate was observed. As compared to other AChE, the enzyme from T. marmorata exhibits the highest affinity to ACh. For all the substrates studied, pH dependence of AChE activity followed the curve with maximum 7.5 for ACh and PrCh, 8.0-8.5 for ATCh and MeCh and 7.5-8.5 for PrTCh. Various salts (MgCl2), KCl, NaCl, NaBr, KI) increased AChE activity, the increase being the highest with MgCl2 (3.3 times) and NaCl (2.5X). Biomolecular rate constants ((k) II) for the interaction of AChE investigated with OPI containing cationic group-methylsulfomethylates, O-ethyl-S-(beta-ethylmercapto) ethylmethylthiophosphonate and O,O-diethyl-S-(beta-ethylmercapto) ethylthiophosphate, as well as methyl iodide O,O-disopropyl-S-(beta-phenylmethylamino) ethylphosphate-were significantly higher as compared with k(II) values for corresponding compounds without the cation. The value of k(II) sharply decreased with the increase in the size of the acyl radicals at phosphorus atom in the molecule of OPI.", "contents": "[Acetylcholinesterase from the electric organ of the ray Torpedo marmorata]. Studies have been made on substrate specificity of acetylcholinesterase (AChE;EC 3-1-1-7) from the electric organ of the ray T. marmorata with respect of choline and thiocholine esters, as well as on the effect of pH, salts and organophosphorus inhibitors (OPI) on the activity of the enzyme. Acetylcholine (ACh), propionycholine (PrCh) acetyl-beta-methylcholine (MeCh), acetylthiocholine ((ATCh) and propionylthiocholine (PrTCh) were hydrolyzed by the enzyme studied at the following relative rates-100: 28.8: 18.3: 87.2: 18.9 correspondingly. In all the cases, inhibition of the enzyme by high concentrations of the substrate was observed. As compared to other AChE, the enzyme from T. marmorata exhibits the highest affinity to ACh. For all the substrates studied, pH dependence of AChE activity followed the curve with maximum 7.5 for ACh and PrCh, 8.0-8.5 for ATCh and MeCh and 7.5-8.5 for PrTCh. Various salts (MgCl2), KCl, NaCl, NaBr, KI) increased AChE activity, the increase being the highest with MgCl2 (3.3 times) and NaCl (2.5X). Biomolecular rate constants ((k) II) for the interaction of AChE investigated with OPI containing cationic group-methylsulfomethylates, O-ethyl-S-(beta-ethylmercapto) ethylmethylthiophosphonate and O,O-diethyl-S-(beta-ethylmercapto) ethylthiophosphate, as well as methyl iodide O,O-disopropyl-S-(beta-phenylmethylamino) ethylphosphate-were significantly higher as compared with k(II) values for corresponding compounds without the cation. The value of k(II) sharply decreased with the increase in the size of the acyl radicals at phosphorus atom in the molecule of OPI."}
{"id": "PMID:3078", "title": "Isolation and properties of tRNA nucleotidyltransferase from wheat embryos.", "content": "From wheat embryos, tRNA nucleotidyltransferase (EC 2.7.7.25) was isolated. By chromatography on Sepharose 6B, DEAE-cellulose and affinity chromatography on tRNA-hydrazyl-Sepharose 4B, 7000-fold purification of the enzyme was achieved. The enzyme required for its activity Mg2+ or Mn2+ ion. ATP inhibited incorporation of CMP from CTP into lupin tRNA, and CTP acted as a competitive inhibitor of AMP incorporation from ATP. The regulatory role of ATP in incorporation of terminal CMP into tRNA is discussed. The incorporation of terminal CMP into tRNA deprived of terminal CCA or CA, was also studied.", "contents": "Isolation and properties of tRNA nucleotidyltransferase from wheat embryos. From wheat embryos, tRNA nucleotidyltransferase (EC 2.7.7.25) was isolated. By chromatography on Sepharose 6B, DEAE-cellulose and affinity chromatography on tRNA-hydrazyl-Sepharose 4B, 7000-fold purification of the enzyme was achieved. The enzyme required for its activity Mg2+ or Mn2+ ion. ATP inhibited incorporation of CMP from CTP into lupin tRNA, and CTP acted as a competitive inhibitor of AMP incorporation from ATP. The regulatory role of ATP in incorporation of terminal CMP into tRNA is discussed. The incorporation of terminal CMP into tRNA deprived of terminal CCA or CA, was also studied."}
{"id": "PMID:3076", "title": "[Electronmicroscopic study of the gravity receptors in ctenophores].", "content": "Secondarily sensitive receptor balancer cells comprise the gravity receptor in the aboral organ-polivalent organ of Ctenophora. Ctenophora are phylogenetically the first animals which created receptor cell supplied with a single flagellar kinocilium connected with the otolithic apparatus. The receptor balancer cells are innervated by the nerve fiber branched off the nerve cells of the aboral ganglion. The localization of AChE, BuChE products of cytochemical reaction on sodium suggests that the cholinergic mechanism may take part in the process of synaptic transmission. Our morphological data cannot exclude an adrenergic mechanizm also.", "contents": "[Electronmicroscopic study of the gravity receptors in ctenophores]. Secondarily sensitive receptor balancer cells comprise the gravity receptor in the aboral organ-polivalent organ of Ctenophora. Ctenophora are phylogenetically the first animals which created receptor cell supplied with a single flagellar kinocilium connected with the otolithic apparatus. The receptor balancer cells are innervated by the nerve fiber branched off the nerve cells of the aboral ganglion. The localization of AChE, BuChE products of cytochemical reaction on sodium suggests that the cholinergic mechanism may take part in the process of synaptic transmission. Our morphological data cannot exclude an adrenergic mechanizm also."}
{"id": "PMID:3079", "title": "Non-specific acetyl-CoA carboxylase and methylmalonyl-CoA carboxyltransferase in Streptomyces noursei var. polifungini.", "content": "1. Acetyl-CoA carboxylase (EC 6.4.1.2) and methylmalonyl-CoA carboxyltransferase (EC 2.1.3.1) have been isolated from mycelia of Streptomyces noursei var. polifungini, and purified about 50-fold. 2. Both enzymes carboxylate acetyl-CoA and propionyl-CoA; the respective Km values are 1.1 and 1.6 mM with acetyl-CoA carboxylase and 2.5 and 1.25 mM with carboxyltransferase. 3. The activities of both enzymes are inhibited by free fatty acids. Almost total inhibition of methylmalonyl-CoA carboxyltransferase was observed by 0.1 mM-butyrate or 0.1 mM-C14-C18 acids. Acetyl-CoA carobxylase was affected to the same extent by these compounds at concentration of about 1 mM. 4. The role of both carboxylating enzymes is biosynthesis of the antibiotic is discussed.", "contents": "Non-specific acetyl-CoA carboxylase and methylmalonyl-CoA carboxyltransferase in Streptomyces noursei var. polifungini. 1. Acetyl-CoA carboxylase (EC 6.4.1.2) and methylmalonyl-CoA carboxyltransferase (EC 2.1.3.1) have been isolated from mycelia of Streptomyces noursei var. polifungini, and purified about 50-fold. 2. Both enzymes carboxylate acetyl-CoA and propionyl-CoA; the respective Km values are 1.1 and 1.6 mM with acetyl-CoA carboxylase and 2.5 and 1.25 mM with carboxyltransferase. 3. The activities of both enzymes are inhibited by free fatty acids. Almost total inhibition of methylmalonyl-CoA carboxyltransferase was observed by 0.1 mM-butyrate or 0.1 mM-C14-C18 acids. Acetyl-CoA carobxylase was affected to the same extent by these compounds at concentration of about 1 mM. 4. The role of both carboxylating enzymes is biosynthesis of the antibiotic is discussed."}
{"id": "PMID:3081", "title": "Preoperative treatment of thyrotoxicosis with a beta-adrenergic blocking agent.", "content": "The clinical usefulness of propranolol as the sole drug in the preoperative treatment of thyrotoxicosis has been investigated. The effect of the drug on the serum levels of thyroxine and triiodothyronine has also been studied. Eight consecutive patients were treated. Four of these showed good clinical response to propranolol and both pre- and postoperative periods were uneventful. Two patients also showed a good clinical response but developed accentuated thyrotoxic symptoms in the immediate postoperative period. One patient showed no clinical response to propranolol therapy and in one further patient the treatment was discontinued because of discomfort. All glands were resected without technical difficulty. They were more vascular and friable after this therapy than after pretreatment with antithyroid drugs and thyroxine. The serum levels of thyroxine and triiodothyronine decreased during propranolol treatment. It is concluded that treatment with propranolol as a sole preoperative drug might be used as an alternative only in cases where conventional therapy is not suitable.", "contents": "Preoperative treatment of thyrotoxicosis with a beta-adrenergic blocking agent. The clinical usefulness of propranolol as the sole drug in the preoperative treatment of thyrotoxicosis has been investigated. The effect of the drug on the serum levels of thyroxine and triiodothyronine has also been studied. Eight consecutive patients were treated. Four of these showed good clinical response to propranolol and both pre- and postoperative periods were uneventful. Two patients also showed a good clinical response but developed accentuated thyrotoxic symptoms in the immediate postoperative period. One patient showed no clinical response to propranolol therapy and in one further patient the treatment was discontinued because of discomfort. All glands were resected without technical difficulty. They were more vascular and friable after this therapy than after pretreatment with antithyroid drugs and thyroxine. The serum levels of thyroxine and triiodothyronine decreased during propranolol treatment. It is concluded that treatment with propranolol as a sole preoperative drug might be used as an alternative only in cases where conventional therapy is not suitable."}
{"id": "PMID:3082", "title": "Reduction of 3-oxosteroids in human liver microsomes.", "content": "The 3alpha- and 3beta-reduction of the following steroids was studied in human liver microsomes: 5alpha-androstane-3,17-dione, 17beta-hydroxy-5alpha-androstan-3-one, 5alpha-pregnane-3,20-dione, 5beta-pregnane-3,20-dione, 3-oxo-5beta-cholanoic acid and 7alpha-hydroxy-5alpha-cholestan-3-one. With NADH as cofactor there was a preferential 3alpha-reduction of the C19- and C21-3-oxo-steroids and a preferential 3beta-reduction of the C24- and C27-3-oxo-steroids. Substitution of NADH with NADPH influenced reduction of the substrates in different ways, indicating the presence of several 3alpha- and 3beta-hydroxysteroid dehydrogenases with different substrate specificity and specificity towards NADH and NADPH. Only small or insignificant sex differences could be observed in the reductions studied.", "contents": "Reduction of 3-oxosteroids in human liver microsomes. The 3alpha- and 3beta-reduction of the following steroids was studied in human liver microsomes: 5alpha-androstane-3,17-dione, 17beta-hydroxy-5alpha-androstan-3-one, 5alpha-pregnane-3,20-dione, 5beta-pregnane-3,20-dione, 3-oxo-5beta-cholanoic acid and 7alpha-hydroxy-5alpha-cholestan-3-one. With NADH as cofactor there was a preferential 3alpha-reduction of the C19- and C21-3-oxo-steroids and a preferential 3beta-reduction of the C24- and C27-3-oxo-steroids. Substitution of NADH with NADPH influenced reduction of the substrates in different ways, indicating the presence of several 3alpha- and 3beta-hydroxysteroid dehydrogenases with different substrate specificity and specificity towards NADH and NADPH. Only small or insignificant sex differences could be observed in the reductions studied."}
{"id": "PMID:3083", "title": "The fractional post-coital test performed in a square capillary tube.", "content": "A new method of examination of post-coital cervical mucus was developed, with special attention to the moving spermatozoa. The test is performed in a square capillary tube (edge 0,8 mm). The migration rate, -- velocity and -- direction are measured by means of an ocular micrometer, which is seen projected over the capillary tube.", "contents": "The fractional post-coital test performed in a square capillary tube. A new method of examination of post-coital cervical mucus was developed, with special attention to the moving spermatozoa. The test is performed in a square capillary tube (edge 0,8 mm). The migration rate, -- velocity and -- direction are measured by means of an ocular micrometer, which is seen projected over the capillary tube."}
{"id": "PMID:3084", "title": "I-cell disease (mucolipidosis II):a report on its pathology.", "content": "The single most characteristic morphological feature in I-cell disease (ICD) is the accumulation of membrane-bound vacuoles in mesenchymal cells (mainly fibroblasts). No true storage can be documented in those vacuoles. That their contents could have been dissolved during fixation or embedding remains however a possibility. Remnants consisting of a few lamellar arrays and of small amounts of fibrillo-granular material are too scarce for histochemical characterization. In hepatocytes large cells in the white pulp of the spleen and in myocardial fibers, vacuoles with fixative insoluble contents have been discovered; they are nowhere very abundant and their specificity is questionable. Because the affected fibroblastic elements represent a small fraction in any organ, most secondary biochemical abnormalities are expected to be detectable only in purely fibroblastic tissues. Our pathological study contributes to the understanding of some of the clinical features characteristic of ICD and stresses major morphological differences between ICD and the many diseases classified as mucopolysaccharidoses and mucolipidoses.", "contents": "I-cell disease (mucolipidosis II):a report on its pathology. The single most characteristic morphological feature in I-cell disease (ICD) is the accumulation of membrane-bound vacuoles in mesenchymal cells (mainly fibroblasts). No true storage can be documented in those vacuoles. That their contents could have been dissolved during fixation or embedding remains however a possibility. Remnants consisting of a few lamellar arrays and of small amounts of fibrillo-granular material are too scarce for histochemical characterization. In hepatocytes large cells in the white pulp of the spleen and in myocardial fibers, vacuoles with fixative insoluble contents have been discovered; they are nowhere very abundant and their specificity is questionable. Because the affected fibroblastic elements represent a small fraction in any organ, most secondary biochemical abnormalities are expected to be detectable only in purely fibroblastic tissues. Our pathological study contributes to the understanding of some of the clinical features characteristic of ICD and stresses major morphological differences between ICD and the many diseases classified as mucopolysaccharidoses and mucolipidoses."}
{"id": "PMID:3085", "title": "Histochemical and morphological changes in human muscle spindle in upper and lower motor neuron lesions.", "content": "The human intrafusal fibers were found to consist of two morphological and three histochemical (ATPase reaction) types. Two types of nuclear bag fibers were seen. Type A showed alkali stable and acid labile and Type B showed acid and alkali stable ATPase reaction. The nuclear chain fibers showed only alkali stable ATPase reaction. In the lower motor neuron atrophy, muscle spindle showed thickening of the capsule, atrophy of the nuclear chain fibers, and splitting of the nuclear bag fibers. ATPase reaction showed targetoid Type B nuclear bag fibers and 2 types of nuclear chain fibers. Oxidative enzymes also showed targetoid nuclear bag and chain fibers. In upper motor neuron atrophy the spindle showed no changes.", "contents": "Histochemical and morphological changes in human muscle spindle in upper and lower motor neuron lesions. The human intrafusal fibers were found to consist of two morphological and three histochemical (ATPase reaction) types. Two types of nuclear bag fibers were seen. Type A showed alkali stable and acid labile and Type B showed acid and alkali stable ATPase reaction. The nuclear chain fibers showed only alkali stable ATPase reaction. In the lower motor neuron atrophy, muscle spindle showed thickening of the capsule, atrophy of the nuclear chain fibers, and splitting of the nuclear bag fibers. ATPase reaction showed targetoid Type B nuclear bag fibers and 2 types of nuclear chain fibers. Oxidative enzymes also showed targetoid nuclear bag and chain fibers. In upper motor neuron atrophy the spindle showed no changes."}
{"id": "PMID:3086", "title": "[Effect of an anxiolytic agent in hay fever].", "content": "In a group of 55 allergic patients with hay fever, and including patients treated by complete placebo, the action of Lorazepam has been studied from both the psycho-somatic and the allergic point of view. This most obviously allergic of all allergic diseases has been especially chosen because it was thought that the psycho-somatic hypothesis would appear at the outset in this condition to be the less apparent. Despite this fact, the anxiolitic effect of Lorazepam and its anti-allergic consequences were conclusive. A parallel study using only placebo treatment, orally and by vaccine, was performed in a few cases. 39 patients out of 45 treated by Temesta and placebo vaccine, had few or very few allergic symptoms. The 10 patients treated by complete placebo (orally and by vaccine) presented this year an acute pollinosis. We find the same parallelism between the allergy and the psycho-somatic aspect.", "contents": "[Effect of an anxiolytic agent in hay fever]. In a group of 55 allergic patients with hay fever, and including patients treated by complete placebo, the action of Lorazepam has been studied from both the psycho-somatic and the allergic point of view. This most obviously allergic of all allergic diseases has been especially chosen because it was thought that the psycho-somatic hypothesis would appear at the outset in this condition to be the less apparent. Despite this fact, the anxiolitic effect of Lorazepam and its anti-allergic consequences were conclusive. A parallel study using only placebo treatment, orally and by vaccine, was performed in a few cases. 39 patients out of 45 treated by Temesta and placebo vaccine, had few or very few allergic symptoms. The 10 patients treated by complete placebo (orally and by vaccine) presented this year an acute pollinosis. We find the same parallelism between the allergy and the psycho-somatic aspect."}
{"id": "PMID:3087", "title": "A case of methylmalonic and propionic acidemia due to methulmalonyl-CoA carbonylmutase apoenzyme deficiency.", "content": "A patient presenting with a deep metabolic acidosis after birth is described. Gas chromatographic analysis of short chain fatty acid and non volatile organic acids revealed the presence of both propionic and methylmalonic acid. In plasma obtained immediately after death the propionic- and methylmalonic acid concentrations were measured after separation of both acids by thin layer chromatography. The propionic acid concentration was about 5 mM while the methylmalonic acid concentration was 2.6 mM. The methylmalonic acid concentration in urine was 6.8 mM. Propionyl-CoA carboxylase activity measured in leucocytes and liver-mitochondria revealed normal values (53 pmoles/min/mg protein and 6.5 nmoles/min/mg protein respectively). 2-14C-Methyl-malonate oxydation in intact fibroblasts was totally blocked in the patient's cells. The methylmalonyl-CoA carbonyl mutase activity was found to be absent in the patient's fibroblasts. Addition of vit. B12 coenzyme to the incubation mixture stimulated 14C-succinate formation in the control cells but not in the patient's cells.", "contents": "A case of methylmalonic and propionic acidemia due to methulmalonyl-CoA carbonylmutase apoenzyme deficiency. A patient presenting with a deep metabolic acidosis after birth is described. Gas chromatographic analysis of short chain fatty acid and non volatile organic acids revealed the presence of both propionic and methylmalonic acid. In plasma obtained immediately after death the propionic- and methylmalonic acid concentrations were measured after separation of both acids by thin layer chromatography. The propionic acid concentration was about 5 mM while the methylmalonic acid concentration was 2.6 mM. The methylmalonic acid concentration in urine was 6.8 mM. Propionyl-CoA carboxylase activity measured in leucocytes and liver-mitochondria revealed normal values (53 pmoles/min/mg protein and 6.5 nmoles/min/mg protein respectively). 2-14C-Methyl-malonate oxydation in intact fibroblasts was totally blocked in the patient's cells. The methylmalonyl-CoA carbonyl mutase activity was found to be absent in the patient's fibroblasts. Addition of vit. B12 coenzyme to the incubation mixture stimulated 14C-succinate formation in the control cells but not in the patient's cells."}
{"id": "PMID:3088", "title": "Enzyme histochemical studies of rabbit bile ducts with and without bile flow.", "content": "The histochemical enzyme pattern in normal, extra-hepatic bile ducts from rabbits was studied. A difference between the duct epithelium and the crypt epithelium was noted mainly in the activity of gamma-glutamyl-transpeptidase and alkaline phosphatase which only stained positively in the crypts. No difference from the normal enzyme pattern was noted after diversion of the bile flow for up to 30 days.", "contents": "Enzyme histochemical studies of rabbit bile ducts with and without bile flow. The histochemical enzyme pattern in normal, extra-hepatic bile ducts from rabbits was studied. A difference between the duct epithelium and the crypt epithelium was noted mainly in the activity of gamma-glutamyl-transpeptidase and alkaline phosphatase which only stained positively in the crypts. No difference from the normal enzyme pattern was noted after diversion of the bile flow for up to 30 days."}
{"id": "PMID:3089", "title": "Survival of anaerobic bacteria during transportation. 1. Experimental investigations on the effect of evacuation of atmospheric air by flushing with carbon dioxide and nitrogen.", "content": "The effect of evacuation of atmospheric air during transportation on recovery of anaerobic bacteria was investigated. Evacuation of atmospheric air from glass tubes by flushing with pure carbon dioxide lowered the content of oxygen to about 0.4 per cent. Three B. fragilis strains and one strain of Fusobacterium mortiferum and of Peptostreptococcus anaerobius were investigated. Bacterial recovery was determined one hour and 24 hours after evacuation of atmospheric air by pure carbon dioxide and pure nitrogen, was compared to bacterial recovery from samples transported with free access to atmospheric air. Evacuation by pure carbon dioxide significantly improved the recovery of one B. fragilis strain after 24 hours of transportation and significantly impaired the recovery of Peptostreptococcus anaerobius after one hour of transportation, while evacuation by pure nitrogen significantly improved the recovery of Peptostreptococcus anaerobius after 24 hours of transportation. In all other cases, however, no statistically significant effect on bacterial recovery was found.", "contents": "Survival of anaerobic bacteria during transportation. 1. Experimental investigations on the effect of evacuation of atmospheric air by flushing with carbon dioxide and nitrogen. The effect of evacuation of atmospheric air during transportation on recovery of anaerobic bacteria was investigated. Evacuation of atmospheric air from glass tubes by flushing with pure carbon dioxide lowered the content of oxygen to about 0.4 per cent. Three B. fragilis strains and one strain of Fusobacterium mortiferum and of Peptostreptococcus anaerobius were investigated. Bacterial recovery was determined one hour and 24 hours after evacuation of atmospheric air by pure carbon dioxide and pure nitrogen, was compared to bacterial recovery from samples transported with free access to atmospheric air. Evacuation by pure carbon dioxide significantly improved the recovery of one B. fragilis strain after 24 hours of transportation and significantly impaired the recovery of Peptostreptococcus anaerobius after one hour of transportation, while evacuation by pure nitrogen significantly improved the recovery of Peptostreptococcus anaerobius after 24 hours of transportation. In all other cases, however, no statistically significant effect on bacterial recovery was found."}
{"id": "PMID:3090", "title": "The spread of the action potential through the T-system in hagfish twitch muscle fibres.", "content": "The input impedance of twitch muscle fibres of the Atlantic hagfish has been measured with sinusoidal transmembrane currents. The apparent specific membrane resistance and capacitance decreased markedly with frequency, and were relatively independent of fibre diameter. A model of the T-system based on anatomical observations, was used to predict the input impedance in the normal solution (artificial sea water). The changes in input impedance produced by glycerol treatment, low chloride solution, reduced pH and isotonic solutions with low ionic strength were easily interpreted in terms of the same model. The model predicts severe attenuation of the action potential if conducted electrotonically by the transverse tubules towards the center of the fibre.", "contents": "The spread of the action potential through the T-system in hagfish twitch muscle fibres. The input impedance of twitch muscle fibres of the Atlantic hagfish has been measured with sinusoidal transmembrane currents. The apparent specific membrane resistance and capacitance decreased markedly with frequency, and were relatively independent of fibre diameter. A model of the T-system based on anatomical observations, was used to predict the input impedance in the normal solution (artificial sea water). The changes in input impedance produced by glycerol treatment, low chloride solution, reduced pH and isotonic solutions with low ionic strength were easily interpreted in terms of the same model. The model predicts severe attenuation of the action potential if conducted electrotonically by the transverse tubules towards the center of the fibre."}
{"id": "PMID:3091", "title": "Withdrawal psychosis: a study of 30 consecutive cases.", "content": "A study was carried out of 30 consecutive patients with withdrawal psychosis who in the period 1972 to 1975 were admitted to a psychiatric department or were attended by the department while hospitalized in a somatic department. There was a clear majority of women among cases of psychosis following drug withdrawal (15 as against four) and a clear majority of men among cases of psychosis following alcohol withdrawal (nine as against two). Competing pathogenetic factors could be considered present in most cases in the last mentioned group. In most cases the abrupt cessation took place in conjunction with admission to hospital, most frequently surgical cases or cases of acute drug toxication. In other cases abrupt cessation was decided upon by the patient himself. Frequently predelirium treatment was either omitted or was given in the form of neuroleptics. Approximately a quarter of the patients initially denied their abuse. The study indicates that withdrawal psychosis can make its debut or become manifest at so late a stage as about the 14th day of the withdrawal phase following use of benzodiazepines and d-propoxiphene. It is further indicated that abrupt cessation of benzodiazepines taken in \"therapeutic\" doses for several years in some instances can give rise to a withdrawal psychosis.", "contents": "Withdrawal psychosis: a study of 30 consecutive cases. A study was carried out of 30 consecutive patients with withdrawal psychosis who in the period 1972 to 1975 were admitted to a psychiatric department or were attended by the department while hospitalized in a somatic department. There was a clear majority of women among cases of psychosis following drug withdrawal (15 as against four) and a clear majority of men among cases of psychosis following alcohol withdrawal (nine as against two). Competing pathogenetic factors could be considered present in most cases in the last mentioned group. In most cases the abrupt cessation took place in conjunction with admission to hospital, most frequently surgical cases or cases of acute drug toxication. In other cases abrupt cessation was decided upon by the patient himself. Frequently predelirium treatment was either omitted or was given in the form of neuroleptics. Approximately a quarter of the patients initially denied their abuse. The study indicates that withdrawal psychosis can make its debut or become manifest at so late a stage as about the 14th day of the withdrawal phase following use of benzodiazepines and d-propoxiphene. It is further indicated that abrupt cessation of benzodiazepines taken in \"therapeutic\" doses for several years in some instances can give rise to a withdrawal psychosis."}
{"id": "PMID:3092", "title": "Nephroangiography in Wegener's granulumatosis. A comparison with panarteritis nodosa.", "content": "Three cases of Wegener's granulomatosis with a classical course are described, 2 of which with fatal outcome in spite of immuno-suppressive therapy. Nephroangiography was performed during the oliguric or anuric phase. The appearances were similar to those encountered in glomerulonephritis and were compared with those in three cases of panarteritis nodosa. Two of these represented the classical form with intrarenal arterial aneurysms; the third was a case of the microscopic type presenting blurred intrarenal arteries with lumen variations and occlusions. These observations support the opinion that Wegener's granulomatosis nodosa are different diseases. Nephroangiography seems to be of value in their differentiation.", "contents": "Nephroangiography in Wegener's granulumatosis. A comparison with panarteritis nodosa. Three cases of Wegener's granulomatosis with a classical course are described, 2 of which with fatal outcome in spite of immuno-suppressive therapy. Nephroangiography was performed during the oliguric or anuric phase. The appearances were similar to those encountered in glomerulonephritis and were compared with those in three cases of panarteritis nodosa. Two of these represented the classical form with intrarenal arterial aneurysms; the third was a case of the microscopic type presenting blurred intrarenal arteries with lumen variations and occlusions. These observations support the opinion that Wegener's granulomatosis nodosa are different diseases. Nephroangiography seems to be of value in their differentiation."}
{"id": "PMID:3093", "title": "The effect of metoprolol --a new selective adrenergic beta1-receptor blocking agent-- in mild hypertension.", "content": "Metoprolol, a new selective adrenergic beta1-receptor blocking drug, has been compared to placebo in a series of 24 women who previously had taken alprenolol and propranolol during a cross-over study. Blood pressure (BP) and heart rate (HR) were significantly reduced during metoprolol treatment compared to placebo. The occurrence of side-effects was similar during treatment with metoprolol and placebo. After the cross-over study the patients continued on metoprolol for more than two years, except for short periods on placebo or propranolol. During this follow-up period BP remained at a similar level when the metoprolol dose was unchanged. Dose reduction (from 50 or 100 mg t.i.d. to 50 or 100 mg b.i.d.) caused no, or only a very slight, increase in BP. No side-effects were reported during long-term treatment.", "contents": "The effect of metoprolol --a new selective adrenergic beta1-receptor blocking agent-- in mild hypertension. Metoprolol, a new selective adrenergic beta1-receptor blocking drug, has been compared to placebo in a series of 24 women who previously had taken alprenolol and propranolol during a cross-over study. Blood pressure (BP) and heart rate (HR) were significantly reduced during metoprolol treatment compared to placebo. The occurrence of side-effects was similar during treatment with metoprolol and placebo. After the cross-over study the patients continued on metoprolol for more than two years, except for short periods on placebo or propranolol. During this follow-up period BP remained at a similar level when the metoprolol dose was unchanged. Dose reduction (from 50 or 100 mg t.i.d. to 50 or 100 mg b.i.d.) caused no, or only a very slight, increase in BP. No side-effects were reported during long-term treatment."}
{"id": "PMID:3094", "title": "Comparison between metoprolol and propranolol as antihypertensive agents. A double-blind cross-over study.", "content": "A new selective beta-adrenergic blocking agent--metoprolol--is compared to a non-selective beta-adrenergic blocking agent--propranolol--according to a double-blind cross-over technique in 23 hypertensive women, who had previously taken alprenolol and propranolol during different periods. No significant differences were found for blood pressure, heart rate, body weight or serum uric acid. No side-effects which could be related to the therapy were seen with either drug.", "contents": "Comparison between metoprolol and propranolol as antihypertensive agents. A double-blind cross-over study. A new selective beta-adrenergic blocking agent--metoprolol--is compared to a non-selective beta-adrenergic blocking agent--propranolol--according to a double-blind cross-over technique in 23 hypertensive women, who had previously taken alprenolol and propranolol during different periods. No significant differences were found for blood pressure, heart rate, body weight or serum uric acid. No side-effects which could be related to the therapy were seen with either drug."}
{"id": "PMID:3095", "title": "Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion.", "content": "A number of hemodynamic, pharmacologic and metabolic interventions were found to change the extent of acute ischemic injury of the myocardium and subsequent necrosis following experimental coronary artery occlusion. Reduction in myocardial damage occurred by decreasing myocardial oxygen demands (beta-adrenergic blocking agents, intra-aortic balloon counterpulsation, external counterpulsation, nitroglycerin, decreasing afterload in hypertensive patients, inhibition of lipolysis, and digitalis in the failing heart); by increasing myocardial oxygen supply either directly (coronary artery reperfusion or elevating arterial pO2),  or through collateral vessels (elevation of coronary perfusion pressure by alpha-adrenergic agonists, intra-aortic balloon counterpulsation); or by increasing plasma osmolality (mannitol, hypertonic glucose); presumably by augmenting anaerobic metabolism (glucose-insulin-potassium, hypertonic glucose); by enhancing transport to the ischemic zone of substrates utilized in energy production (hyaluronidase); by protecting against autolytic and heterolytic damage (hydrocortisone, cobra venom factor, aprotinin). Augmentation of myocardial ischemic damage occurred as a consequence of increasing myocardial oxygen requirements (isoproterenol, glucagon, ouabain, bretylium tosylate, tachycardia); by decreasing myocardial oxygen supply either directly (hypoxia, anemia) or through reduction of collateral flow (hemorrhagic hypotension, minoxidil) or by decreasing substrate availability glycemia). Pilot studies have been carried out in patients with hyaluronidase, nitroglycerin, intra-aortic balloon counterpulsation, beta-blocking agents and Arfonad and have shown that these interventions may also reduce myocardial damage, suggesting that the concept of reduction in infarct size following coronary occlusion is applicable clinically.", "contents": "Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion. A number of hemodynamic, pharmacologic and metabolic interventions were found to change the extent of acute ischemic injury of the myocardium and subsequent necrosis following experimental coronary artery occlusion. Reduction in myocardial damage occurred by decreasing myocardial oxygen demands (beta-adrenergic blocking agents, intra-aortic balloon counterpulsation, external counterpulsation, nitroglycerin, decreasing afterload in hypertensive patients, inhibition of lipolysis, and digitalis in the failing heart); by increasing myocardial oxygen supply either directly (coronary artery reperfusion or elevating arterial pO2),  or through collateral vessels (elevation of coronary perfusion pressure by alpha-adrenergic agonists, intra-aortic balloon counterpulsation); or by increasing plasma osmolality (mannitol, hypertonic glucose); presumably by augmenting anaerobic metabolism (glucose-insulin-potassium, hypertonic glucose); by enhancing transport to the ischemic zone of substrates utilized in energy production (hyaluronidase); by protecting against autolytic and heterolytic damage (hydrocortisone, cobra venom factor, aprotinin). Augmentation of myocardial ischemic damage occurred as a consequence of increasing myocardial oxygen requirements (isoproterenol, glucagon, ouabain, bretylium tosylate, tachycardia); by decreasing myocardial oxygen supply either directly (hypoxia, anemia) or through reduction of collateral flow (hemorrhagic hypotension, minoxidil) or by decreasing substrate availability glycemia). Pilot studies have been carried out in patients with hyaluronidase, nitroglycerin, intra-aortic balloon counterpulsation, beta-blocking agents and Arfonad and have shown that these interventions may also reduce myocardial damage, suggesting that the concept of reduction in infarct size following coronary occlusion is applicable clinically."}
{"id": "PMID:3096", "title": "Factors of importance for the degree of ischemic injury in the isolated rat heart.", "content": "Isolated working rat hearts were made ischemic by introducing a one-way aortic ball valve. After the ischemic period the hearts were perfused in a retrograde non-working way for 30 min. Flow rates, glycogen, ATP, and creatine-phosphate went down during the time of ischemia, whereas tissue lactate accumulated. For shorter periods of ischemia these values were normalized but after 30 min of ischemia the hearts seemed to be irreversibly damaged. There was a leakage of GOT, GPT, LDH, and CPK from all hearts when ischemic from 5 to 30 min. Different factors that might be of importance for the degree of ischemic injury were tested. The injury tended to be more severe at higher heart rates. Addition of adrenaline 10(-6)M resulted in excessive myocardial damage. A variation of pH from 7.1 to 7.7 did not alter the effects of the ischemic injury. One group of rats were injected with adrenaline for 8 weeks to simulate chronic stress. When hearts from these rats were made ischemic they were more prone to fail compared to controls. The failing hearts, on the other hand, had a lower leakage of enzymes, possibly due to a less severe myocardial damage. A high mechanical performance and a normal noradrenaline content of the hearts are key factors for the development of myocardial infarction, as indicated by this study.", "contents": "Factors of importance for the degree of ischemic injury in the isolated rat heart. Isolated working rat hearts were made ischemic by introducing a one-way aortic ball valve. After the ischemic period the hearts were perfused in a retrograde non-working way for 30 min. Flow rates, glycogen, ATP, and creatine-phosphate went down during the time of ischemia, whereas tissue lactate accumulated. For shorter periods of ischemia these values were normalized but after 30 min of ischemia the hearts seemed to be irreversibly damaged. There was a leakage of GOT, GPT, LDH, and CPK from all hearts when ischemic from 5 to 30 min. Different factors that might be of importance for the degree of ischemic injury were tested. The injury tended to be more severe at higher heart rates. Addition of adrenaline 10(-6)M resulted in excessive myocardial damage. A variation of pH from 7.1 to 7.7 did not alter the effects of the ischemic injury. One group of rats were injected with adrenaline for 8 weeks to simulate chronic stress. When hearts from these rats were made ischemic they were more prone to fail compared to controls. The failing hearts, on the other hand, had a lower leakage of enzymes, possibly due to a less severe myocardial damage. A high mechanical performance and a normal noradrenaline content of the hearts are key factors for the development of myocardial infarction, as indicated by this study."}
{"id": "PMID:3098", "title": "Double-blind study of the effect of cardioselective beta-blockade on chest pain in acute myocardial infarction.", "content": "A double-blind study including three different cardioselective beta-blockers, practolol, H 87/07 and metoprolol, was performed in 54 patients with acute myocardial infarction and chest pain shortly after onset of symptoms. Transmural infarctions were found in 42 patients while 12 patients had nontransmural infarctions. Chest pain and the product of heart rate and systolic blood pressure were significantly reduced in the beta-blocker groups whereas no changes were seen after saline. All patients with nontransmural infarctions and 14 out of 29 with transmural infarctions got pain relief lasting for at least 30 min. None of the patients developed signs of left ventricular backward failure, shock, or bradycardia. A decrease in ST segment elevation was observed in all the transmural infarctions after beta-blockade. No changes in ST segment elevation were found after analgesics when given after saline, but in some cases an increase was seen in this parameter when analgesics were given due to insufficient pain relief after beta-blockers or due to return of chest pain. It is suggested that pain relief by beta-blockers indicates decrease of myocardial ischemia.", "contents": "Double-blind study of the effect of cardioselective beta-blockade on chest pain in acute myocardial infarction. A double-blind study including three different cardioselective beta-blockers, practolol, H 87/07 and metoprolol, was performed in 54 patients with acute myocardial infarction and chest pain shortly after onset of symptoms. Transmural infarctions were found in 42 patients while 12 patients had nontransmural infarctions. Chest pain and the product of heart rate and systolic blood pressure were significantly reduced in the beta-blocker groups whereas no changes were seen after saline. All patients with nontransmural infarctions and 14 out of 29 with transmural infarctions got pain relief lasting for at least 30 min. None of the patients developed signs of left ventricular backward failure, shock, or bradycardia. A decrease in ST segment elevation was observed in all the transmural infarctions after beta-blockade. No changes in ST segment elevation were found after analgesics when given after saline, but in some cases an increase was seen in this parameter when analgesics were given due to insufficient pain relief after beta-blockers or due to return of chest pain. It is suggested that pain relief by beta-blockers indicates decrease of myocardial ischemia."}
{"id": "PMID:3102", "title": "Multiple endocrine adenomatosis syndromes.", "content": "MEA I and II are two genetically distinct tumor endocrinopathies, both showing autosomal dominant inheritance. Little overlap exists between these conditions, and that which is present can be explained on the basis of two mutually exclusive factors: (1) the secondary consequences of hormone excess on another endocrine gland or (2) the fact that both tumor syndromes appear to result from genetically faulty differentiation of neuroectoderm. A seemingly disproportionate amount of effort has been expended on study of the MEA syndromes. However, there would seen to be ample justification for this interest: 1) The MEA syndromes, unlike most neoplastic conditions, are hereditary and can be readily detected and more expeditiously treated; 2) hormone radioimmunoassay has greatly facilitated diagnosis in asymptomatic individuals; and (3) probably most importantly, study of these syndromes has provided considerable insight into the embryologic origin of the endocrine system. It is conceivable that knowledge gained from these conditions may stimulate further inquiry into the processes whereby neoplasia occurs in endocrine tissue and thus lead the way to the development of effective therapy for a host of hormone-producing tumors.", "contents": "Multiple endocrine adenomatosis syndromes. MEA I and II are two genetically distinct tumor endocrinopathies, both showing autosomal dominant inheritance. Little overlap exists between these conditions, and that which is present can be explained on the basis of two mutually exclusive factors: (1) the secondary consequences of hormone excess on another endocrine gland or (2) the fact that both tumor syndromes appear to result from genetically faulty differentiation of neuroectoderm. A seemingly disproportionate amount of effort has been expended on study of the MEA syndromes. However, there would seen to be ample justification for this interest: 1) The MEA syndromes, unlike most neoplastic conditions, are hereditary and can be readily detected and more expeditiously treated; 2) hormone radioimmunoassay has greatly facilitated diagnosis in asymptomatic individuals; and (3) probably most importantly, study of these syndromes has provided considerable insight into the embryologic origin of the endocrine system. It is conceivable that knowledge gained from these conditions may stimulate further inquiry into the processes whereby neoplasia occurs in endocrine tissue and thus lead the way to the development of effective therapy for a host of hormone-producing tumors."}
{"id": "PMID:3108", "title": "Folic acid absorption in regional enteritis.", "content": "The authors have investigated intestinal absorption of folic acid by jejunal perfusion with a triple lumen tube in five subjects with regional enteritis. The subjects' intestinal disabilities ranged from terminal ileitis to short bowel syndrome. Two had steatorrhea and two had low serum folate levels. Absorption of pteroylglutamic acid was normal in all five. This suggests that folic acid deficiency, common in this disorder, is largely caused by malnutrition, not malabsorption.", "contents": "Folic acid absorption in regional enteritis. The authors have investigated intestinal absorption of folic acid by jejunal perfusion with a triple lumen tube in five subjects with regional enteritis. The subjects' intestinal disabilities ranged from terminal ileitis to short bowel syndrome. Two had steatorrhea and two had low serum folate levels. Absorption of pteroylglutamic acid was normal in all five. This suggests that folic acid deficiency, common in this disorder, is largely caused by malnutrition, not malabsorption."}
{"id": "PMID:3109", "title": "Acid, neutral, and alkaline hydrolases in arthritic synovium.", "content": "The levels of six lysosomal enzymes (acid phosphatase, beta-acetylglucosaminidase, cathepsin D, beta-galactosidase, arylsulfatase A, and beta-glucuronidase) and four neutral and alkaline hydrolases (esterase, inorganic phyrophosphatase, alkaline phosphatase, and 5'-nucleotidase) were measured in osteoarthritic, rheumatoid and control synovia. All enzyme levels in diseased synovium except esterase values in osteoarthritis were significantly elevated compared with controls. The mean values of the group of acid hydrolases and the group of neutral and alkaline hydrolases in osteoarthritic synovia were 1.9- and 2.0-fold greater than those of control specimens. In rheumatoid synovia, the values were 4.2- and 4.5 fold greater than control for the same enzymes. Levels in rheumatoid synovia were significantly higher than those in osteoarthritic synovia with the exception of 5'-nucleotidase. Only a limited correlation between the extents of inflammation present in the synovia and the levels of a lysosomal marker enzyme (cathepsin D) was observed. These results demonstrate that whatever the mechanism, increased levels of acid hydrolases as well as certain neutral and alkaline hydrolases are present in osteoarthritic and rheumatoid synovia, and these enzymes are probably contained in the synovial lining cells.", "contents": "Acid, neutral, and alkaline hydrolases in arthritic synovium. The levels of six lysosomal enzymes (acid phosphatase, beta-acetylglucosaminidase, cathepsin D, beta-galactosidase, arylsulfatase A, and beta-glucuronidase) and four neutral and alkaline hydrolases (esterase, inorganic phyrophosphatase, alkaline phosphatase, and 5'-nucleotidase) were measured in osteoarthritic, rheumatoid and control synovia. All enzyme levels in diseased synovium except esterase values in osteoarthritis were significantly elevated compared with controls. The mean values of the group of acid hydrolases and the group of neutral and alkaline hydrolases in osteoarthritic synovia were 1.9- and 2.0-fold greater than those of control specimens. In rheumatoid synovia, the values were 4.2- and 4.5 fold greater than control for the same enzymes. Levels in rheumatoid synovia were significantly higher than those in osteoarthritic synovia with the exception of 5'-nucleotidase. Only a limited correlation between the extents of inflammation present in the synovia and the levels of a lysosomal marker enzyme (cathepsin D) was observed. These results demonstrate that whatever the mechanism, increased levels of acid hydrolases as well as certain neutral and alkaline hydrolases are present in osteoarthritic and rheumatoid synovia, and these enzymes are probably contained in the synovial lining cells."}
{"id": "PMID:3111", "title": "Effects of acute metabolic acidosis on parathyroid hormone action and calcium mobilization.", "content": "Mechanisms through which metabolic acidosis increases calcium mobilization have been investigated in thyroparathyroidectomized rats with induction of acute metabolic acidosis by infusing NH4C1 intravenously. Acute metabolic acidosis directly raised serum calcium concentration and augmented the effect of parathyroid hormone (PTH) to raise serum calcium concentration. The same effects of metabolic acidosis were observed in rats with surgically removed intestines and bilateral nephrectomy, suggesting that acute metabolic acidosis directly increases calcium mobilization from bone and augments the effect of PTH to mobilize calcium from bone. In the kidney, acidosis directly inhibited the tubular reabsorption of calcium, but augmented the effect of PTH to increase tubular reabsorption of calcium. Acidosis had no measurable effect on calcitonin action.", "contents": "Effects of acute metabolic acidosis on parathyroid hormone action and calcium mobilization. Mechanisms through which metabolic acidosis increases calcium mobilization have been investigated in thyroparathyroidectomized rats with induction of acute metabolic acidosis by infusing NH4C1 intravenously. Acute metabolic acidosis directly raised serum calcium concentration and augmented the effect of parathyroid hormone (PTH) to raise serum calcium concentration. The same effects of metabolic acidosis were observed in rats with surgically removed intestines and bilateral nephrectomy, suggesting that acute metabolic acidosis directly increases calcium mobilization from bone and augments the effect of PTH to mobilize calcium from bone. In the kidney, acidosis directly inhibited the tubular reabsorption of calcium, but augmented the effect of PTH to increase tubular reabsorption of calcium. Acidosis had no measurable effect on calcitonin action."}
{"id": "PMID:3112", "title": "Metabolism of histamine in secreting and isolated canine stomach.", "content": "Total 14C activity in juice secreted by gastric pouches of six dogs and seven isolated canine stomachs was determined in response to intravenous and intra-arterial infusions of histamine and [14C]histamine. The proportions of 14C attributable to histamine, Nalpha-methylhistamine (NalphaMeH), Nalpha,Nalpha-dimethylhistamine (NalphaNalphaMe2H), N-telle-methylhistamine (NtauMeH), imidazole acetic acid (ImAA), N-methylimidazole acetic acid (NtauMeImAA), acetylhistamine (AcH), and histaminol (HOH) were defined using thin-layer chromatography. Similar estimates were made at the end of infusions on blood, gastric mucosa, and gastric muscle. Methylation was the major, or sole, route of metabolism of histamine in the gastric mucosa, and the major product was inactive NtauMeH. Small quantities of the active NalphaMe derivatives, particularly NalphaNalphaMe2H, were identified in both the juice and mucosa. Little or no ImAA, NtauMeImAA, AcH, and HOH were present in juice from isolated stomachs while they did occur in the juice from intact dogs, demonstrating they are extragastric metabolites of histamine. A major mucosal function of methylation of histamine is inactivation, although NalphaMe derivatives formed may play a role in the secretagogue action of histamine.", "contents": "Metabolism of histamine in secreting and isolated canine stomach. Total 14C activity in juice secreted by gastric pouches of six dogs and seven isolated canine stomachs was determined in response to intravenous and intra-arterial infusions of histamine and [14C]histamine. The proportions of 14C attributable to histamine, Nalpha-methylhistamine (NalphaMeH), Nalpha,Nalpha-dimethylhistamine (NalphaNalphaMe2H), N-telle-methylhistamine (NtauMeH), imidazole acetic acid (ImAA), N-methylimidazole acetic acid (NtauMeImAA), acetylhistamine (AcH), and histaminol (HOH) were defined using thin-layer chromatography. Similar estimates were made at the end of infusions on blood, gastric mucosa, and gastric muscle. Methylation was the major, or sole, route of metabolism of histamine in the gastric mucosa, and the major product was inactive NtauMeH. Small quantities of the active NalphaMe derivatives, particularly NalphaNalphaMe2H, were identified in both the juice and mucosa. Little or no ImAA, NtauMeImAA, AcH, and HOH were present in juice from isolated stomachs while they did occur in the juice from intact dogs, demonstrating they are extragastric metabolites of histamine. A major mucosal function of methylation of histamine is inactivation, although NalphaMe derivatives formed may play a role in the secretagogue action of histamine."}
{"id": "PMID:3113", "title": "Intracellular bicarbonate of skeletal muscle under different metabolic states.", "content": "Intracellular bicarbonate of single muscle fibers in vivo was measured by a direct electrometric method simultaneously with the membrane PD in rats under seven different metabolic states. From the measured intracellular bicarbonate values and the PCO2, the bicarbonate equilibrium potential and the intracellular pH were calculated. The mean intracellular [HCO3-] under normal control conditions was 10.3 +/- 0.7 mM (SE). The intracellular bicarbonate fell significantly in both chronic metabolic acidosis and chronic K+ depletion. In contrast, intracellular bicarbonate was elevated in chronic metabolic alkalosis, K+ loading, and Na+ depletion. Taking intracellular pH as an index of the acid-base status of cells, we find that whereas the calculated cell pH decreased along with the cell bicarbonate in both chronic metabolic acidosis and K+ depletion, cell pH increased along with the bicarbonate only in chronic metabolic alkalosis. Cell pH was unchanged in both chronic K+ loading and Na+ depletion.", "contents": "Intracellular bicarbonate of skeletal muscle under different metabolic states. Intracellular bicarbonate of single muscle fibers in vivo was measured by a direct electrometric method simultaneously with the membrane PD in rats under seven different metabolic states. From the measured intracellular bicarbonate values and the PCO2, the bicarbonate equilibrium potential and the intracellular pH were calculated. The mean intracellular [HCO3-] under normal control conditions was 10.3 +/- 0.7 mM (SE). The intracellular bicarbonate fell significantly in both chronic metabolic acidosis and chronic K+ depletion. In contrast, intracellular bicarbonate was elevated in chronic metabolic alkalosis, K+ loading, and Na+ depletion. Taking intracellular pH as an index of the acid-base status of cells, we find that whereas the calculated cell pH decreased along with the cell bicarbonate in both chronic metabolic acidosis and K+ depletion, cell pH increased along with the bicarbonate only in chronic metabolic alkalosis. Cell pH was unchanged in both chronic K+ loading and Na+ depletion."}
{"id": "PMID:3114", "title": "Effect of acid lumen pH on potassium transport in renal cortical collecting tubules.", "content": "In order to determine the effect of acid lumen pH on renal tubular potassium transport, cortical collecting tubules were dissected from rabbit kidneys and perfused in vitro. When the pH of the perfusate was lowered from 7.4 to 6.8, potassium secretion into the tubule lumen decreased by an average of 47%. The transepithelial voltage increased from a mean value of -32 mV (lumen negative) at pH 7.4 to -51 mV at PH 6.8. Net sodium absorption from the tubule lumen was essentially unchanged (5% mean decrease). Transepithelial voltage and potassium secretion returned to control values when the pH of the perfusate was raised to 7.4. Alterations in pH of the bath had no comparable effect on the transepithelial voltage, whether the bath pH was increased or decreased. We conclude that a decrease in the pH of the tubule fluid of itself inhibits active potassium secretion in this tubule segment, providing an additional explanation for the decrease in potassium excretion found in acidosis. The negative voltage (presumably caused by sodium absorption out of the lumen) is increased under these conditions, possibly because of reduction of a smaller counterbalancing positive voltage caused by potassium secretion into the lumen.", "contents": "Effect of acid lumen pH on potassium transport in renal cortical collecting tubules. In order to determine the effect of acid lumen pH on renal tubular potassium transport, cortical collecting tubules were dissected from rabbit kidneys and perfused in vitro. When the pH of the perfusate was lowered from 7.4 to 6.8, potassium secretion into the tubule lumen decreased by an average of 47%. The transepithelial voltage increased from a mean value of -32 mV (lumen negative) at pH 7.4 to -51 mV at PH 6.8. Net sodium absorption from the tubule lumen was essentially unchanged (5% mean decrease). Transepithelial voltage and potassium secretion returned to control values when the pH of the perfusate was raised to 7.4. Alterations in pH of the bath had no comparable effect on the transepithelial voltage, whether the bath pH was increased or decreased. We conclude that a decrease in the pH of the tubule fluid of itself inhibits active potassium secretion in this tubule segment, providing an additional explanation for the decrease in potassium excretion found in acidosis. The negative voltage (presumably caused by sodium absorption out of the lumen) is increased under these conditions, possibly because of reduction of a smaller counterbalancing positive voltage caused by potassium secretion into the lumen."}
{"id": "PMID:3115", "title": "Reflex sympathetic tachycardia during intravenous infusions in chronic spinal cats.", "content": "The reflex tachycardia elicited by rapid intravenous infusions of a blood substitute was studied in 21 chronic cats with spinal sections at C8. All animals could breath spontaneously. The day after section the average resting heart rate (HR) and arterial pressure (AP) were 109 beats/min and 98/67 mmHg, respectively. Vagal blockade with atropine (0.5-0.7 mg/kg iv) was performed prior to each infusion, increasing the average HR To 127 beats/min. In 39 infusions in 21 cats the average increase in HR was 10 beats/min (range from -6 to +22 beats/min). A tachycardia was observed in all but five trials, four of which were obtained in two cats that subsequently responded with a tachycardia. In seven animals the neural circuit mediating the response was partially or totally interrupted by section of several thoracic dorsal roots (T1-T4 or T1-T6) and of the spinal cord at the inferior level of these sections (between T6 and T7). The tachycardia response was progressively reduced and finally abolished by these procedures. These experiments indicate that spinal neural mechanisms are likely to contribute to the phenomenon first described by Bainbridge.", "contents": "Reflex sympathetic tachycardia during intravenous infusions in chronic spinal cats. The reflex tachycardia elicited by rapid intravenous infusions of a blood substitute was studied in 21 chronic cats with spinal sections at C8. All animals could breath spontaneously. The day after section the average resting heart rate (HR) and arterial pressure (AP) were 109 beats/min and 98/67 mmHg, respectively. Vagal blockade with atropine (0.5-0.7 mg/kg iv) was performed prior to each infusion, increasing the average HR To 127 beats/min. In 39 infusions in 21 cats the average increase in HR was 10 beats/min (range from -6 to +22 beats/min). A tachycardia was observed in all but five trials, four of which were obtained in two cats that subsequently responded with a tachycardia. In seven animals the neural circuit mediating the response was partially or totally interrupted by section of several thoracic dorsal roots (T1-T4 or T1-T6) and of the spinal cord at the inferior level of these sections (between T6 and T7). The tachycardia response was progressively reduced and finally abolished by these procedures. These experiments indicate that spinal neural mechanisms are likely to contribute to the phenomenon first described by Bainbridge."}
{"id": "PMID:3116", "title": "Sudden potential drop in bullfrog gastric mucosa.", "content": "The previously reported sudden potential drop (SPD), which occurs under anoxia in 10% CO2, has been further explored. We find several conditions necessary for this effect: 1) anoxia; 2) serosal pH less than 7.1;3) presence of chloride; and 4) a PD, either spontaneous or voltage clamped, which changes across the region of 10 mV, serosal positive. With the first three conditions satisfied, a reversible decrease in measured resistance can be produced at will by changing the clamp voltage. In the anoxic, low-resistance state, changes in K+ or C1- concentration give little change in voltage, showing that the increased conductivity is not selective for either ion. A model is proposed containing a shunt-resistance element whose resistance is a step function of PD. This model can mimic the responses of the tissue and provides a working model for the SPD.", "contents": "Sudden potential drop in bullfrog gastric mucosa. The previously reported sudden potential drop (SPD), which occurs under anoxia in 10% CO2, has been further explored. We find several conditions necessary for this effect: 1) anoxia; 2) serosal pH less than 7.1;3) presence of chloride; and 4) a PD, either spontaneous or voltage clamped, which changes across the region of 10 mV, serosal positive. With the first three conditions satisfied, a reversible decrease in measured resistance can be produced at will by changing the clamp voltage. In the anoxic, low-resistance state, changes in K+ or C1- concentration give little change in voltage, showing that the increased conductivity is not selective for either ion. A model is proposed containing a shunt-resistance element whose resistance is a step function of PD. This model can mimic the responses of the tissue and provides a working model for the SPD."}
{"id": "PMID:3117", "title": "Cancer of the undescended or maldescended testis.", "content": "An analysis of 45 cryptorchids (by history or examination) with a testicular cancer treated at Memorial Hospital, between 1934 and 1973, is presented. Twenty-five patients had the cryptorchid state repaired at ages four to 27 years, either spontaneously or by orchiopexy or hormonal therapy. Ipsilateral (24) or contralateral (one) intrascrotal testis tumors developed four to 47 years later. Twenty cryptorchid patients presented with ipsilateral inguinal (eleven), abdominal (seven), or contralateral intrascrotal (two) tumors. There were 18 pure seminomas, 17 embryonal carcinomas, nine teratocarcinomas, and one reticulum cell sarcoma. Five year survival rates as estimated by the product-limit method were 60% for the unrepaired cases and 41% for the repaired cases. The survival seems to follow histologic type and anatomical stage, whether the testis is within the scrotum or not. Five year survival similarly estimated was 78% in the seminomas and 29% in the other tumors. Twelve of thirteen survivors (including nine with seminoma) received postoperative irradiation to the regional lymphatics and eleven were without recurrent tumor for periods ranging from six to 28 years.", "contents": "Cancer of the undescended or maldescended testis. An analysis of 45 cryptorchids (by history or examination) with a testicular cancer treated at Memorial Hospital, between 1934 and 1973, is presented. Twenty-five patients had the cryptorchid state repaired at ages four to 27 years, either spontaneously or by orchiopexy or hormonal therapy. Ipsilateral (24) or contralateral (one) intrascrotal testis tumors developed four to 47 years later. Twenty cryptorchid patients presented with ipsilateral inguinal (eleven), abdominal (seven), or contralateral intrascrotal (two) tumors. There were 18 pure seminomas, 17 embryonal carcinomas, nine teratocarcinomas, and one reticulum cell sarcoma. Five year survival rates as estimated by the product-limit method were 60% for the unrepaired cases and 41% for the repaired cases. The survival seems to follow histologic type and anatomical stage, whether the testis is within the scrotum or not. Five year survival similarly estimated was 78% in the seminomas and 29% in the other tumors. Twelve of thirteen survivors (including nine with seminoma) received postoperative irradiation to the regional lymphatics and eleven were without recurrent tumor for periods ranging from six to 28 years."}
{"id": "PMID:3120", "title": "Use of protease inhibitor (trasylol) and heparin in cardiorespiratory resuscitation. II. Gasometric investigations of arterial blood.", "content": "The purpose of the present work was to assess the effect of trasylol--an inhibitor of proteases--and heparin on gasometric values in arterial blood during cardio-respiratory resuscitation. The investigations were carried out on rabbits in three experimental groups. In group I the simplest resuscitation procedures were applied: artificial respiration with AMBU self-expanding bag and heart massage. In group II oxygen was given for respiration, heart massage was applied, cardiac, vasoactive and alkalinizing drugs were given. Group III received the above drugs and procedures but trasylol and herparin were used additionally. Cardiac arrest was obtained by means of acute hypoxia following suxamethonium administration. The investigations showed that in groups I and II despite resuscitation management arterial hypoxaemia and metabolic acidosis persisted while in group III a certain return of normal gasometric values was observed and the animals in this group survived the experiment.", "contents": "Use of protease inhibitor (trasylol) and heparin in cardiorespiratory resuscitation. II. Gasometric investigations of arterial blood. The purpose of the present work was to assess the effect of trasylol--an inhibitor of proteases--and heparin on gasometric values in arterial blood during cardio-respiratory resuscitation. The investigations were carried out on rabbits in three experimental groups. In group I the simplest resuscitation procedures were applied: artificial respiration with AMBU self-expanding bag and heart massage. In group II oxygen was given for respiration, heart massage was applied, cardiac, vasoactive and alkalinizing drugs were given. Group III received the above drugs and procedures but trasylol and herparin were used additionally. Cardiac arrest was obtained by means of acute hypoxia following suxamethonium administration. The investigations showed that in groups I and II despite resuscitation management arterial hypoxaemia and metabolic acidosis persisted while in group III a certain return of normal gasometric values was observed and the animals in this group survived the experiment."}
{"id": "PMID:3127", "title": "Porcine malignant hyperthermia induced by halothane and succinylcholine: failure of treatment with procaine or procainamide.", "content": "Metabolic, hemodynamic and neuroendocrine responses to the combined use of halothane and succinylcholine (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH). Constant-volume ventilation was used, and no therapy was instituted. The overall response in susceptible swine was fulminant, in that it involved the rapid onset of SCh-induced MH combined with the more severe metabolic, endocrine, and cardiovascular effects of halothane-induced MH. Maximal changes in VO2 were equivalent with either drug or both combined, while changes in lactate, potassium (K+), pH, and catecholamines were perhaps synergistic. Utilizing similar measurements, procaine or procainamide was used in 20 susceptible swine in attempts to prevent MH initiated by halothane, SCh, or both. Recommended therapeutic doses of either drug did not prevent characteristic MH changes in oxygen consumption, cardiac output, lactate, K+, pH, catecholamines, or temperature.", "contents": "Porcine malignant hyperthermia induced by halothane and succinylcholine: failure of treatment with procaine or procainamide. Metabolic, hemodynamic and neuroendocrine responses to the combined use of halothane and succinylcholine (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH). Constant-volume ventilation was used, and no therapy was instituted. The overall response in susceptible swine was fulminant, in that it involved the rapid onset of SCh-induced MH combined with the more severe metabolic, endocrine, and cardiovascular effects of halothane-induced MH. Maximal changes in VO2 were equivalent with either drug or both combined, while changes in lactate, potassium (K+), pH, and catecholamines were perhaps synergistic. Utilizing similar measurements, procaine or procainamide was used in 20 susceptible swine in attempts to prevent MH initiated by halothane, SCh, or both. Recommended therapeutic doses of either drug did not prevent characteristic MH changes in oxygen consumption, cardiac output, lactate, K+, pH, catecholamines, or temperature."}
{"id": "PMID:3129", "title": "[Comparative study of neuraminidases from \"Diplococcus pneumoniae\" and \"Clostridium perfringens\"].", "content": "Neuraminidases have been purified from the culture medium of two microorganisms, one aerobic, Diplococcus neumoniae, the other anaerobic, Clostridium perfringens. The enzymatic properties of the 2 neuraminidases have been studied (pH optimum; effect of cations; activity toward different substrates: neuraminyllactose, dilactaminyllacto-N-tetraose, gangliosides, alpha1-acid glycoprotein, Collocalia glycoprotein, ovine submaxillary mucin, porcin intestinal and human bronchial mucins).", "contents": "[Comparative study of neuraminidases from \"Diplococcus pneumoniae\" and \"Clostridium perfringens\"]. Neuraminidases have been purified from the culture medium of two microorganisms, one aerobic, Diplococcus neumoniae, the other anaerobic, Clostridium perfringens. The enzymatic properties of the 2 neuraminidases have been studied (pH optimum; effect of cations; activity toward different substrates: neuraminyllactose, dilactaminyllacto-N-tetraose, gangliosides, alpha1-acid glycoprotein, Collocalia glycoprotein, ovine submaxillary mucin, porcin intestinal and human bronchial mucins)."}
{"id": "PMID:3130", "title": "[Carbohydrate containing media for the detection of urease in \"Klebsiella\"].", "content": "Sone strains of Klebsiella pneumoniae and K. oxytoca grown on nutrient agar may appear \"urease negative\" in a Ferguson type reagent medium after a 24 h incubation at 37 degrees C. Amongst such 147 so called urease negative strains, urease has been detected within a few hours in 79 strains, when bacteria have grown on media containing carbohydrates (Kligler iron agar, Drigalski lactose agar, SS agar and Worfel-Ferguson sucrose medium). Acid production by carbohydrate fermentation increases urease production by Klebsiella: pH 4 is the most convenient pH for urease synthesis by these bacteria. The other 68 strains have been considered as urease-less Klebsiella. The best results are obtained from culture on Worfel-Ferguson sucrose medium: urea hydrolysis is positive--on an average-after 1 hour and 30 minutes when detected in a Ferguson type reagent medium, and after 2 hours and 35 minutes when detected in a Christensen reagent medium.", "contents": "[Carbohydrate containing media for the detection of urease in \"Klebsiella\"]. Sone strains of Klebsiella pneumoniae and K. oxytoca grown on nutrient agar may appear \"urease negative\" in a Ferguson type reagent medium after a 24 h incubation at 37 degrees C. Amongst such 147 so called urease negative strains, urease has been detected within a few hours in 79 strains, when bacteria have grown on media containing carbohydrates (Kligler iron agar, Drigalski lactose agar, SS agar and Worfel-Ferguson sucrose medium). Acid production by carbohydrate fermentation increases urease production by Klebsiella: pH 4 is the most convenient pH for urease synthesis by these bacteria. The other 68 strains have been considered as urease-less Klebsiella. The best results are obtained from culture on Worfel-Ferguson sucrose medium: urea hydrolysis is positive--on an average-after 1 hour and 30 minutes when detected in a Ferguson type reagent medium, and after 2 hours and 35 minutes when detected in a Christensen reagent medium."}
{"id": "PMID:3131", "title": "[Ferrous ion oxidation and uranium solubilization from a lowgrade ore by \"Thiobacillus ferrooxidans\" (author's transl)].", "content": "The microbiological oxidation of ferrous ion and the extraction of uranium from a low-grade ore has been studied using an adapted strain of Thiobacillus ferrooxidans. The effect of temperature, pH, volumetric oxygen transfer coefficient, K1a, and aeration number, Ia, on the activity of the microorganism has been determined. The activation energy for ferrous iron oxidation was calculated to be - 13.9 +/- 0.1 kcal/mole and inactivation (thermal death of bacteria) 53.3 +/- 0.2 kcal/mole. Temperature coefficient, Q10, was estimated to be 1.8. Uranium extraction varied between 80 and 100%.", "contents": "[Ferrous ion oxidation and uranium solubilization from a lowgrade ore by \"Thiobacillus ferrooxidans\" (author's transl)]. The microbiological oxidation of ferrous ion and the extraction of uranium from a low-grade ore has been studied using an adapted strain of Thiobacillus ferrooxidans. The effect of temperature, pH, volumetric oxygen transfer coefficient, K1a, and aeration number, Ia, on the activity of the microorganism has been determined. The activation energy for ferrous iron oxidation was calculated to be - 13.9 +/- 0.1 kcal/mole and inactivation (thermal death of bacteria) 53.3 +/- 0.2 kcal/mole. Temperature coefficient, Q10, was estimated to be 1.8. Uranium extraction varied between 80 and 100%."}
{"id": "PMID:3133", "title": "Ethanol and galactose metabolism as influenced by 4-methylpyrazole in alcoholics with and without nutritional deficiencies. Preliminary report of a new approach to pathogenesis and treatment in alcoholic liver disease.", "content": "4-Methyl pyrazole (4-MP, a specific inhibitor of alcohol dehydrogenase) reduced ethanol elimination by 30-50% and completely removed the ethanol-induced inhibition of galactose elimination in 2 control subjects. Ethanol elimination was accelerated in 2 alcoholics with adequate nutrition, but the effect of 4-MP was comparable to that in controls. In 2 other alcoholic subjects, who reported poor nutritional intake, intermediate rates of ethanol elimination were observed and 4-MP had almost no effect on ethanol or galactose elimination. These results suggest that alcohol abuse may result in an increased contribution to ethanol elimination by pathways other than that involving alcohol dehydrogenase (ADH) and that the decreased contribution from ADH, possibly potentiated by inadequate nutrition, may diminish the ethanol-induced shift in the NAD-coupled redox state. Since liver damage produced by alcohol abuse is believed to be related to changes from the normal redox state caused by ethanol, these results may explain why alcoholic liver damage is uncommon in alcoholics living on a  marginal diet. Since 4-MP effectively eliminates the ethanol-induced shift in the redox state, a therapeutic trial with 4-MP in alcoholics with a high risk for liver disease is indicated.", "contents": "Ethanol and galactose metabolism as influenced by 4-methylpyrazole in alcoholics with and without nutritional deficiencies. Preliminary report of a new approach to pathogenesis and treatment in alcoholic liver disease. 4-Methyl pyrazole (4-MP, a specific inhibitor of alcohol dehydrogenase) reduced ethanol elimination by 30-50% and completely removed the ethanol-induced inhibition of galactose elimination in 2 control subjects. Ethanol elimination was accelerated in 2 alcoholics with adequate nutrition, but the effect of 4-MP was comparable to that in controls. In 2 other alcoholic subjects, who reported poor nutritional intake, intermediate rates of ethanol elimination were observed and 4-MP had almost no effect on ethanol or galactose elimination. These results suggest that alcohol abuse may result in an increased contribution to ethanol elimination by pathways other than that involving alcohol dehydrogenase (ADH) and that the decreased contribution from ADH, possibly potentiated by inadequate nutrition, may diminish the ethanol-induced shift in the NAD-coupled redox state. Since liver damage produced by alcohol abuse is believed to be related to changes from the normal redox state caused by ethanol, these results may explain why alcoholic liver damage is uncommon in alcoholics living on a  marginal diet. Since 4-MP effectively eliminates the ethanol-induced shift in the redox state, a therapeutic trial with 4-MP in alcoholics with a high risk for liver disease is indicated."}
{"id": "PMID:3144", "title": "A method for the regulation of microbial population density during continuous culture at high growth rates.", "content": "A method for the continuous culture of microorganisms is described which employs growth-dependent pH changes to control the rate of addition of fresh medium to a culture vessel. The apparatus (the \"phauxostat\") supports, at constant pH, long-term continuous culture at rates near or at the maximum of which the organisms are capable. The buffering capacity of the inflowing medium determines the steady-state population density of the culture, but the rate of growth is independent of the buffering capacity. The fundamental theory of operation is tested and some basic parameters of growth are estimated using Escherichia coli B growing continuously in media containing glucose, glycerol or DL-lactate.", "contents": "A method for the regulation of microbial population density during continuous culture at high growth rates. A method for the continuous culture of microorganisms is described which employs growth-dependent pH changes to control the rate of addition of fresh medium to a culture vessel. The apparatus (the \"phauxostat\") supports, at constant pH, long-term continuous culture at rates near or at the maximum of which the organisms are capable. The buffering capacity of the inflowing medium determines the steady-state population density of the culture, but the rate of growth is independent of the buffering capacity. The fundamental theory of operation is tested and some basic parameters of growth are estimated using Escherichia coli B growing continuously in media containing glucose, glycerol or DL-lactate."}
{"id": "PMID:3145", "title": "Pyruvate fermentation in Rhodospirillum rubrum and after transfer from aerobic to anaerobic conditions in the dark.", "content": "The fermentative metabolism of Rhodospirillum rubrum (strain Ha, F1, S1) was studied after transfering the cells from aerobic to anaerobic dark culture conditions. Pyruvate was metabolized mainly to acetate and formate, and to a lesser extent to CO2 and priopionate, by all strains. Therefore, pyruvate formate lyase would appear to be the characteristic key enzyme of the dark anaerobic fermentation metabolism in R. rubrum. Strain F1 and S1 metabolized the formate further to H2 and CO2. It is concluded that this cleavage was catalysed by a formate hydrogen lyase system. Strain Ha was unable to metabolize formate. The cleavage of formate and the synthesis of poly-beta-hydroxy-butyric acid were increased by a low pH value (approximately 6.5). Fermentation equations and schemes of the pyruvate metabolism are discussed.", "contents": "Pyruvate fermentation in Rhodospirillum rubrum and after transfer from aerobic to anaerobic conditions in the dark. The fermentative metabolism of Rhodospirillum rubrum (strain Ha, F1, S1) was studied after transfering the cells from aerobic to anaerobic dark culture conditions. Pyruvate was metabolized mainly to acetate and formate, and to a lesser extent to CO2 and priopionate, by all strains. Therefore, pyruvate formate lyase would appear to be the characteristic key enzyme of the dark anaerobic fermentation metabolism in R. rubrum. Strain F1 and S1 metabolized the formate further to H2 and CO2. It is concluded that this cleavage was catalysed by a formate hydrogen lyase system. Strain Ha was unable to metabolize formate. The cleavage of formate and the synthesis of poly-beta-hydroxy-butyric acid were increased by a low pH value (approximately 6.5). Fermentation equations and schemes of the pyruvate metabolism are discussed."}
{"id": "PMID:3146", "title": "The influence of foster-home care on psychiatric patients.", "content": "Adult patients placed into foster families by six administrations in three provinces of Canada were oberved at time of placement and followed up 18 months later. Over this period, they exhibited a substantial decline in symptoms-almost as great as with similar patients retained in the hospital. However, there was virtually no improvement in social functioning, despite the fact that the use of foster homes has been advocated mainly for the resocialization that was expected to occur there. In discussing the reasons for this paradoxical finding, recommendations are offered regarding the use of foster homes by mental health administrations.", "contents": "The influence of foster-home care on psychiatric patients. Adult patients placed into foster families by six administrations in three provinces of Canada were oberved at time of placement and followed up 18 months later. Over this period, they exhibited a substantial decline in symptoms-almost as great as with similar patients retained in the hospital. However, there was virtually no improvement in social functioning, despite the fact that the use of foster homes has been advocated mainly for the resocialization that was expected to occur there. In discussing the reasons for this paradoxical finding, recommendations are offered regarding the use of foster homes by mental health administrations."}
{"id": "PMID:3147", "title": "Sialic acid in thyroglobulin. II. Influence of sialic acid on ionization of tyrosine residues.", "content": "During electrophoresis in polyacrylamide gel at pH 9-5, it was noticed that sialic acid-poor thyroglobulin contains fewer low molecular weight fragments than sialic acid-rich thyroglobulin. Splitting off of sialic acid diminishes thenumber of phenolic groups of tyrosine, MIT, DIT and T4, which dissociate below pH 12-5. This phenomenon was interpreted as a result of lowered hydrophilia of these regions of the thyroglobulin molecule which contains tyrosine and its iodinated derivatives.", "contents": "Sialic acid in thyroglobulin. II. Influence of sialic acid on ionization of tyrosine residues. During electrophoresis in polyacrylamide gel at pH 9-5, it was noticed that sialic acid-poor thyroglobulin contains fewer low molecular weight fragments than sialic acid-rich thyroglobulin. Splitting off of sialic acid diminishes thenumber of phenolic groups of tyrosine, MIT, DIT and T4, which dissociate below pH 12-5. This phenomenon was interpreted as a result of lowered hydrophilia of these regions of the thyroglobulin molecule which contains tyrosine and its iodinated derivatives."}
{"id": "PMID:3148", "title": "Prevention of experimental gastric ulcers in rats by dial derivatives.", "content": "In 111 rats divided into 5 groups, Ipronal (5-allyl-5-(beta-hydroxypropyl)-barbituric acid) protected rats from development of experimental ulceration of the gastric mucosa twice as effectively as diallylbarbituric acid and compound D2H (5-isopropyl-5-(beta-hydroxypropyl)-barbituric acid). Compound D1S (alpha-allophanyl-alpha-allyl-gamma-valerolactone) was devoid of this action.", "contents": "Prevention of experimental gastric ulcers in rats by dial derivatives. In 111 rats divided into 5 groups, Ipronal (5-allyl-5-(beta-hydroxypropyl)-barbituric acid) protected rats from development of experimental ulceration of the gastric mucosa twice as effectively as diallylbarbituric acid and compound D2H (5-isopropyl-5-(beta-hydroxypropyl)-barbituric acid). Compound D1S (alpha-allophanyl-alpha-allyl-gamma-valerolactone) was devoid of this action."}
{"id": "PMID:3150", "title": "Kawasaki disease. Relationship with infantile periarteritis nodosa.", "content": "Until 1972, Kawasaki disease, or acute febrile infantile mucocutaneous lymph node syndrome (MCLS), was considered in Japan to be a nonfatal disease with a favorable prognosis. Based on the findings from two autopsy cases of MCLS, we believe that sudden and unexpected death during convalescence may be due to arterial lesions, especially those involving the coronary artery, that resemble those of periarteritis nodosa. Of 29 autopsy cases of MCLS, gathered from all over Japan, all exhibited arteritis lesions (eg, aneurysm due to coronary arteritis). Such vascular pathological findings may in fact represent the same entity as infantile periarteritis nodosa. Whether infantile periarteritis nodosa can be identified with the adult type is still debatable. The particular manifestations of infantile periarteritis nodosa might be related to severe vasculitis. Autopsy cases of infantile periarteritis nodosa without MCLS manifestations are being collected and studied.", "contents": "Kawasaki disease. Relationship with infantile periarteritis nodosa. Until 1972, Kawasaki disease, or acute febrile infantile mucocutaneous lymph node syndrome (MCLS), was considered in Japan to be a nonfatal disease with a favorable prognosis. Based on the findings from two autopsy cases of MCLS, we believe that sudden and unexpected death during convalescence may be due to arterial lesions, especially those involving the coronary artery, that resemble those of periarteritis nodosa. Of 29 autopsy cases of MCLS, gathered from all over Japan, all exhibited arteritis lesions (eg, aneurysm due to coronary arteritis). Such vascular pathological findings may in fact represent the same entity as infantile periarteritis nodosa. Whether infantile periarteritis nodosa can be identified with the adult type is still debatable. The particular manifestations of infantile periarteritis nodosa might be related to severe vasculitis. Autopsy cases of infantile periarteritis nodosa without MCLS manifestations are being collected and studied."}
{"id": "PMID:3151", "title": "Portal hypertension and gastric lesions in the rat.", "content": "Gastric lesions occurred spontaneously and were increased in number by seven hours of restraint stress in rats with portal vein constriction (PVC). Vagotomy and pyloroplasty protected the congested stomach from erosion formation with stress. Major weight loss occurred two days after PVC, but not thereafter. Platelet counts were decreased in intact and splenectomized rats with portal hypertension, but prothrombin time, partial thromboplastin time, and fibrinogen were unaffected, and histological stains failed to demonstrate thrombin in the gastric blood vessels. The oxygen pressure (PO2) of the gastric luminal fluid was decreased at day 2, but was normal at day 4 after PVC. Hypersection of acid and abnormal acid equilibration were not observed in the stomach. Gastric congestion, weight loss, and possibly portasystemic shunting of blood contributed to the higher incidence of gastric erosions with portal hypertension.", "contents": "Portal hypertension and gastric lesions in the rat. Gastric lesions occurred spontaneously and were increased in number by seven hours of restraint stress in rats with portal vein constriction (PVC). Vagotomy and pyloroplasty protected the congested stomach from erosion formation with stress. Major weight loss occurred two days after PVC, but not thereafter. Platelet counts were decreased in intact and splenectomized rats with portal hypertension, but prothrombin time, partial thromboplastin time, and fibrinogen were unaffected, and histological stains failed to demonstrate thrombin in the gastric blood vessels. The oxygen pressure (PO2) of the gastric luminal fluid was decreased at day 2, but was normal at day 4 after PVC. Hypersection of acid and abnormal acid equilibration were not observed in the stomach. Gastric congestion, weight loss, and possibly portasystemic shunting of blood contributed to the higher incidence of gastric erosions with portal hypertension."}
{"id": "PMID:3154", "title": "Scanning electron microscopy studies in muscular dystrophy.", "content": "Scanning electron microscopy of unmanipulated erythrocytes from patients with myotonic dystrophy or Duchenne dystrophy and patients who were Duchenne carriers showed a large increase in the number of stomatocytes over the number in normal controls. No specific morhologic changes that would differentiate any of the dystrophic patients from one another were seen. Adverse conditions such as washing before fixation or extreme pH produced a greater change in erythrocytes from these patients than in those from normal controls.", "contents": "Scanning electron microscopy studies in muscular dystrophy. Scanning electron microscopy of unmanipulated erythrocytes from patients with myotonic dystrophy or Duchenne dystrophy and patients who were Duchenne carriers showed a large increase in the number of stomatocytes over the number in normal controls. No specific morhologic changes that would differentiate any of the dystrophic patients from one another were seen. Adverse conditions such as washing before fixation or extreme pH produced a greater change in erythrocytes from these patients than in those from normal controls."}
{"id": "PMID:3153", "title": "Comparison of the biological effects in rat of high doses of two 4-amino-7-chloroquinoline derivatives: chloroquine and glafenine.", "content": "When given orally in elevated but nonlethal doses (150 to 450 mg/kg, on 2 consecutive days), glafenine induces in rats (body weight 100 g) a transient nephritis with an increase in blood urea, hypertrophy of adrenals, and some changes in the serum proteinogram. These effects do not appear to be due to the 4-amino-7-chloroquinoline structure from which glafenine is derived, as they are not observed with the structural analogue chloroquine given at equimolar doses under the same conditions. Further, they do not appear to be due to glycerol, the by-product of metabolic glafenine hydrolysis. The responsible molecule appears to be either glafenine itself or its acid metabolite 4-(0-carboxyphenylamino) 7-chloroquinoline.", "contents": "Comparison of the biological effects in rat of high doses of two 4-amino-7-chloroquinoline derivatives: chloroquine and glafenine. When given orally in elevated but nonlethal doses (150 to 450 mg/kg, on 2 consecutive days), glafenine induces in rats (body weight 100 g) a transient nephritis with an increase in blood urea, hypertrophy of adrenals, and some changes in the serum proteinogram. These effects do not appear to be due to the 4-amino-7-chloroquinoline structure from which glafenine is derived, as they are not observed with the structural analogue chloroquine given at equimolar doses under the same conditions. Further, they do not appear to be due to glycerol, the by-product of metabolic glafenine hydrolysis. The responsible molecule appears to be either glafenine itself or its acid metabolite 4-(0-carboxyphenylamino) 7-chloroquinoline."}
{"id": "PMID:3152", "title": "A comparative study on the irreversible binding of labeled halothane trichlorofluoromethane, chloroform, and carbon tetrachloride to hepatic protein and lipids in vitro and in vivo.", "content": "1) After intraperitoneal injection of labeled CCl4, CHCl3, and halothane in mice, 14C is preferentially bound to liver endoplasmic protein and lipid. A considerable activity is also associated with mitochondrial constituents. Maximal protein binding (nmol/mg): CCl4: 2.8 (0.5 hrs); CHCl3: 11.5 (6 hrs); halothane: 5 (6 hrs). Lipid binding: CCl4: 6.4 (5 min); CHCl3: 8 (4 hrs); halothane: 13.5 (2 hrs). The form of the binding curves in microsomal and mitochondrial protein and lipid differed with the individual haloalkanes. 2) The irreversible (covalent) binding of 14C from labeled haloalkanes in anaerobic suspensions of isolated rabbit liver microsomes and NADPH after 30 min was for protein (lipid) (nmol/mg): CCl4: 15 (58); CHCl3: 3.4 (3.2); halothane: 2.3 (10); trichlorofluoromethane: 6.5 (30). Anerobic incubation favored dehalogenation, but CHCl3 metabolism and irreversible binding requires oxygen. The greatest differences in the in vitro \"covalent\" binding rates were observed with CHCl3 in rat, mouse, and rabbit. 3) Altered microsomal cytochrome P-450 concentrations in newborn animals, or produced by pretreatment of rats with phenobarbital, 3-methylcholanthrene (MC), or CoCl2 effected similar, but not proportional changes in the rates of irreversible protein and lipid binding. Upon addition of CCl4 the difference of light absorption of reduced liver microsomes from MC-pretreated rats containing cytochrome P-448 appeared at 452 nm. The irreversible binding rate in these microsomes was also increased. The small accleration in irreversible binding in liver microsomes from rats pretreated with isopropanol is not proportional to the high increase of CCl4 toxicity. 4) Practically no binding to added, soluble albumin or RNA was observed in microsomal incubates. However, 14C is bound to the nicotine-adenine dinucleotides of the NADPH system. All haloalkanes produced a similar increase of NADPH oxidation in incubates of rabbit liver microsomes and NADPH.", "contents": "A comparative study on the irreversible binding of labeled halothane trichlorofluoromethane, chloroform, and carbon tetrachloride to hepatic protein and lipids in vitro and in vivo. 1) After intraperitoneal injection of labeled CCl4, CHCl3, and halothane in mice, 14C is preferentially bound to liver endoplasmic protein and lipid. A considerable activity is also associated with mitochondrial constituents. Maximal protein binding (nmol/mg): CCl4: 2.8 (0.5 hrs); CHCl3: 11.5 (6 hrs); halothane: 5 (6 hrs). Lipid binding: CCl4: 6.4 (5 min); CHCl3: 8 (4 hrs); halothane: 13.5 (2 hrs). The form of the binding curves in microsomal and mitochondrial protein and lipid differed with the individual haloalkanes. 2) The irreversible (covalent) binding of 14C from labeled haloalkanes in anaerobic suspensions of isolated rabbit liver microsomes and NADPH after 30 min was for protein (lipid) (nmol/mg): CCl4: 15 (58); CHCl3: 3.4 (3.2); halothane: 2.3 (10); trichlorofluoromethane: 6.5 (30). Anerobic incubation favored dehalogenation, but CHCl3 metabolism and irreversible binding requires oxygen. The greatest differences in the in vitro \"covalent\" binding rates were observed with CHCl3 in rat, mouse, and rabbit. 3) Altered microsomal cytochrome P-450 concentrations in newborn animals, or produced by pretreatment of rats with phenobarbital, 3-methylcholanthrene (MC), or CoCl2 effected similar, but not proportional changes in the rates of irreversible protein and lipid binding. Upon addition of CCl4 the difference of light absorption of reduced liver microsomes from MC-pretreated rats containing cytochrome P-448 appeared at 452 nm. The irreversible binding rate in these microsomes was also increased. The small accleration in irreversible binding in liver microsomes from rats pretreated with isopropanol is not proportional to the high increase of CCl4 toxicity. 4) Practically no binding to added, soluble albumin or RNA was observed in microsomal incubates. However, 14C is bound to the nicotine-adenine dinucleotides of the NADPH system. All haloalkanes produced a similar increase of NADPH oxidation in incubates of rabbit liver microsomes and NADPH."}
{"id": "PMID:3160", "title": "Interaction of thermostable direct hemolysin of Vibrio parahaemolyticus with human erythrocytes.", "content": "The interaction between thermostable direct hemolysin produced by Vibrio parahaemolyticus WP-1 and human erythrocytes was studied. The lysis of human erythrocytes by the hemolysin was dependent of temperature and no hemolysis occurred at low temperature (0-4 C), but the hemolysin was adsorbed on human erythrocytes even at low temperature. No hemolysis was observed when antihemolysin antiserum was mixed with the hemolysin and human erythrocytes at zero time. On the other hand, lysis of the cells by hemolysin was not completely inhibited when the antiserum was added during the lag time and the inhibitory effect decreased with delay in the time of addition of antiserum. The inhibitory effect of the antiserum decreased with increase in the incubation temperature, increase in the concentration of divalent cations, and decrease in pH. These results suggest that lysis of human erythrocytes by the hemolysin is at least a two-step process consisting of adsorption of the hemolysin to human erythrocytes and the step(s) following adsorption.", "contents": "Interaction of thermostable direct hemolysin of Vibrio parahaemolyticus with human erythrocytes. The interaction between thermostable direct hemolysin produced by Vibrio parahaemolyticus WP-1 and human erythrocytes was studied. The lysis of human erythrocytes by the hemolysin was dependent of temperature and no hemolysis occurred at low temperature (0-4 C), but the hemolysin was adsorbed on human erythrocytes even at low temperature. No hemolysis was observed when antihemolysin antiserum was mixed with the hemolysin and human erythrocytes at zero time. On the other hand, lysis of the cells by hemolysin was not completely inhibited when the antiserum was added during the lag time and the inhibitory effect decreased with delay in the time of addition of antiserum. The inhibitory effect of the antiserum decreased with increase in the incubation temperature, increase in the concentration of divalent cations, and decrease in pH. These results suggest that lysis of human erythrocytes by the hemolysin is at least a two-step process consisting of adsorption of the hemolysin to human erythrocytes and the step(s) following adsorption."}
{"id": "PMID:3161", "title": "Deoxyribonucleic acid polymerases of Euglena gracilis. Purification and properties of two distinct deoxyribonucleic acid polymerases of high molecular weight.", "content": "Two DNA polymerases of high molecular weight, pol A (mol.wt. 190 000) and pol B (mol.wt. 240 ooo), have been purified 6300-fold and 1600-fold respectively from an extramitochondrial supernatant of a bleached strain of Euglena gracilis. They have very similar requirements when assayed with an 'activated'-DNA primer-template [the optimum conditions of pH and ionic (K+ and Mn2+) composition being 7.2, 25 mM and 0.2 mM respectively]. 0.2 mM-Mn2+ was about 1.5-2-fold as effective as 2 mM-Mg2+, owing to substrate activation by deoxyribonucleoside 5'-triphosphates in the presence of Mn2+. Km values for the triphosphates in the absence of activation were about 10(-6)M with Mn2+ and 8 X 10(-6) M with Mg2+ for both enzymes. They were inhibited to the same extent by N-ethylmaleimide, novobiocin and o-phenanthroline, but differed in their chromatographic behaviour on DEAE-cellulose and in their electrophoretic mobilities on polyacrylamide gel. No evidence was found for the existence in these cells of a DNA polymerase of low molecular weight, but there were indications that a third enzyme of high molecular weight might exist.", "contents": "Deoxyribonucleic acid polymerases of Euglena gracilis. Purification and properties of two distinct deoxyribonucleic acid polymerases of high molecular weight. Two DNA polymerases of high molecular weight, pol A (mol.wt. 190 000) and pol B (mol.wt. 240 ooo), have been purified 6300-fold and 1600-fold respectively from an extramitochondrial supernatant of a bleached strain of Euglena gracilis. They have very similar requirements when assayed with an 'activated'-DNA primer-template [the optimum conditions of pH and ionic (K+ and Mn2+) composition being 7.2, 25 mM and 0.2 mM respectively]. 0.2 mM-Mn2+ was about 1.5-2-fold as effective as 2 mM-Mg2+, owing to substrate activation by deoxyribonucleoside 5'-triphosphates in the presence of Mn2+. Km values for the triphosphates in the absence of activation were about 10(-6)M with Mn2+ and 8 X 10(-6) M with Mg2+ for both enzymes. They were inhibited to the same extent by N-ethylmaleimide, novobiocin and o-phenanthroline, but differed in their chromatographic behaviour on DEAE-cellulose and in their electrophoretic mobilities on polyacrylamide gel. No evidence was found for the existence in these cells of a DNA polymerase of low molecular weight, but there were indications that a third enzyme of high molecular weight might exist."}
{"id": "PMID:3162", "title": "Deoxyribonucleic acid polymerases of Euglena gracilis. Primer-template utilization of and enzyme activities associated with the two deoxyribonucleic acid polymerases of high molecular weight.", "content": "The two high-molecular-weight DNA polymerases from Euglena gracilis, pol A (mol. wt. 190 000) and pol B (mol. wt. 240 000), were differentiated on the basis of associated enzymic activities and primer-template utilization. Neither enzyme had endodeoxyribonuclease activity, but pol B, like pol B of yeast and the corresponding enzyme from Tetrahymena pyriformis, exhibited at least one other nuclease activity directed against denatured DNA and the RNA of an RNA-DNA hybrid. These nuclease functions preferred an alkaline pH and Mg2+. Pol B also exhibited nucleoside diphosphokinase activity. Both enzymes were active with 'activated' DNA and poly[d(A-T)] as primer-templates and were sensitive, especially pol B, to inhibition by excess of native or heat-denatured DNA. Pol B also utilized oligo[d(T)] and poly(A) templates under certain conditions, whereas pol A exhibited only slight activity with poly[d(A)]. (U)6 was not used as a primer by either enzyme.", "contents": "Deoxyribonucleic acid polymerases of Euglena gracilis. Primer-template utilization of and enzyme activities associated with the two deoxyribonucleic acid polymerases of high molecular weight. The two high-molecular-weight DNA polymerases from Euglena gracilis, pol A (mol. wt. 190 000) and pol B (mol. wt. 240 000), were differentiated on the basis of associated enzymic activities and primer-template utilization. Neither enzyme had endodeoxyribonuclease activity, but pol B, like pol B of yeast and the corresponding enzyme from Tetrahymena pyriformis, exhibited at least one other nuclease activity directed against denatured DNA and the RNA of an RNA-DNA hybrid. These nuclease functions preferred an alkaline pH and Mg2+. Pol B also exhibited nucleoside diphosphokinase activity. Both enzymes were active with 'activated' DNA and poly[d(A-T)] as primer-templates and were sensitive, especially pol B, to inhibition by excess of native or heat-denatured DNA. Pol B also utilized oligo[d(T)] and poly(A) templates under certain conditions, whereas pol A exhibited only slight activity with poly[d(A)]. (U)6 was not used as a primer by either enzyme."}
{"id": "PMID:3163", "title": "Purification and properties of 6-phosphogluconate dehydrogenase from rabbit mammary gland.", "content": "1. 6-Phosphogluconate dehydrogenase from rabbit mammary gland was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. The molecular weight of the subunit is 52 000. The enzyme was purified 150-fold with a final specific activity of 20 mumol of NADP+ reduced/min per mg of protein and overall yield of 3%. The molecular weight of the native enzyme is estimated to be 104 000 from gel-filtration studies. The final purification step was carried out by affinity chromatography with NADP+-Sepharose. 2. The Km values for 6-phosphogluconate and NADP+ are approx. 54 muM and 23 muM respectively. 3. Citrate and pyrophosphate are competitive inhibitors of the enzyme with respect to both 6-phosphogluconate and NADP+. 4. MgCl2 affects the apparent Km for NADP+ at saturating concentrations of 6-phosphogluconate.", "contents": "Purification and properties of 6-phosphogluconate dehydrogenase from rabbit mammary gland. 1. 6-Phosphogluconate dehydrogenase from rabbit mammary gland was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. The molecular weight of the subunit is 52 000. The enzyme was purified 150-fold with a final specific activity of 20 mumol of NADP+ reduced/min per mg of protein and overall yield of 3%. The molecular weight of the native enzyme is estimated to be 104 000 from gel-filtration studies. The final purification step was carried out by affinity chromatography with NADP+-Sepharose. 2. The Km values for 6-phosphogluconate and NADP+ are approx. 54 muM and 23 muM respectively. 3. Citrate and pyrophosphate are competitive inhibitors of the enzyme with respect to both 6-phosphogluconate and NADP+. 4. MgCl2 affects the apparent Km for NADP+ at saturating concentrations of 6-phosphogluconate."}
{"id": "PMID:3164", "title": "Protein chromatography on adsorbents with hydrophobic and ionic groups. Some properties of N-(3-carboxypropionyl)aminodecyl-sepharose and its interaction with wheat-germ aspartate transcarbamoylase.", "content": "1. The charge state of two derivatives of Sepharose prepared by the CNBr activation method were studied by acid-base titration and by ion-exchange chromatography. Dodecyl-Sepharose exhibited cationic groups (21mumol/ml of settled gel; pKa=9.6) that were tentatively assigned to the coupling isourea group. 2. CPAD-Sepharose [N-(3-carboxypropionyl)aminodecyl-Sepharose] has anionic (carboxyl) groups (pKa=4.5) and cationic groups (pKa=9.6) in roughly equal concentrations (e coupling group. CPAD-Sepharose is slightly negatively charged at pH 7.0 and substantially negatively charged at pH 8.5. 3. The pKa values of dodecyl-Sepharose and CPAD-Sepharose are unaffected by a 100-fold increase in the concentration of KCl. 4. CPAD-Sepharose has considerable affinity for wheat-germ aspartate transcarbamoylase at pH 8.5 when the adsorbent and enzyme are both negatively charged. The interaction involves the C10 chain but is relatively moderate compared with C10 chains associated only with positive charge. 5. Desorption of the enzyme adsorbed to CPAD-Sepharose can be achieved by raising the pH to increase the electrostatic repulsion, or by introducing the detergent sodium deoxycholate. Acetone and butan-1-ol also weaken the adsorption at pH 8.5. 6. High concentrations of sodium acetate or sodium phosphate induced the enzyme to bind more tightly to CPAD-Sepharose. 7. These results are discussed in terms of a 'repulsion-controlled' model or hydrophobic chromatography.", "contents": "Protein chromatography on adsorbents with hydrophobic and ionic groups. Some properties of N-(3-carboxypropionyl)aminodecyl-sepharose and its interaction with wheat-germ aspartate transcarbamoylase. 1. The charge state of two derivatives of Sepharose prepared by the CNBr activation method were studied by acid-base titration and by ion-exchange chromatography. Dodecyl-Sepharose exhibited cationic groups (21mumol/ml of settled gel; pKa=9.6) that were tentatively assigned to the coupling isourea group. 2. CPAD-Sepharose [N-(3-carboxypropionyl)aminodecyl-Sepharose] has anionic (carboxyl) groups (pKa=4.5) and cationic groups (pKa=9.6) in roughly equal concentrations (e coupling group. CPAD-Sepharose is slightly negatively charged at pH 7.0 and substantially negatively charged at pH 8.5. 3. The pKa values of dodecyl-Sepharose and CPAD-Sepharose are unaffected by a 100-fold increase in the concentration of KCl. 4. CPAD-Sepharose has considerable affinity for wheat-germ aspartate transcarbamoylase at pH 8.5 when the adsorbent and enzyme are both negatively charged. The interaction involves the C10 chain but is relatively moderate compared with C10 chains associated only with positive charge. 5. Desorption of the enzyme adsorbed to CPAD-Sepharose can be achieved by raising the pH to increase the electrostatic repulsion, or by introducing the detergent sodium deoxycholate. Acetone and butan-1-ol also weaken the adsorption at pH 8.5. 6. High concentrations of sodium acetate or sodium phosphate induced the enzyme to bind more tightly to CPAD-Sepharose. 7. These results are discussed in terms of a 'repulsion-controlled' model or hydrophobic chromatography."}
{"id": "PMID:3165", "title": "The effect of acid proteinase inhibitors on chicken pepsin.", "content": "1. The activity of chicken pepsin was partially inhibited by dimethyl-(2-hydroxy-5-nitrobenzyl)sulphonium bromide, but was unaffected by p-bromophenacyl bromide. 2. In the presence of Cu2+, diazoacetylnorleucine methyl ester completely inactivated chicken pepsin with the incorporation of 1 mol/mol. The mechanism of the reaction was similar to that with pig pepsin. 3. Chicken pepsin was completely inactivated by 2-diazo-4-bromoacetophenone in the presence of Cu2+. 4. Chicken pepsin was almost completely inactivated by 1,2-epoxy-3-(p-nitrophenoxy)propane at 25 degrees C, 3-4mol of inhibitor/mol being incorporated. The reaction at 10 degrees C was investigated briefly. 5. Calf chymosin was inactivated by 1,2-epoxy-3-(p-nitrophenoxy)propane at 10 degrees C, the incorporation of 1 mol/mol being required for complete inhibition. 6. The characteristics of the reactions of chicken pepsin with the above compounds were compared with those of other acid proteinases.", "contents": "The effect of acid proteinase inhibitors on chicken pepsin. 1. The activity of chicken pepsin was partially inhibited by dimethyl-(2-hydroxy-5-nitrobenzyl)sulphonium bromide, but was unaffected by p-bromophenacyl bromide. 2. In the presence of Cu2+, diazoacetylnorleucine methyl ester completely inactivated chicken pepsin with the incorporation of 1 mol/mol. The mechanism of the reaction was similar to that with pig pepsin. 3. Chicken pepsin was completely inactivated by 2-diazo-4-bromoacetophenone in the presence of Cu2+. 4. Chicken pepsin was almost completely inactivated by 1,2-epoxy-3-(p-nitrophenoxy)propane at 25 degrees C, 3-4mol of inhibitor/mol being incorporated. The reaction at 10 degrees C was investigated briefly. 5. Calf chymosin was inactivated by 1,2-epoxy-3-(p-nitrophenoxy)propane at 10 degrees C, the incorporation of 1 mol/mol being required for complete inhibition. 6. The characteristics of the reactions of chicken pepsin with the above compounds were compared with those of other acid proteinases."}
{"id": "PMID:3166", "title": "The purification and properties of pig spleen phosphofructokinase.", "content": "Pig spleen phosphofructokinase has been purified 800-fold with a yield of 17%. Two isoenzymes that appear to be kinetically identical can be separated by DEAE-cellulose column chromatography. In common with the enzyme from other mammalian sources, the spleen enzyme has a pH optimum of 8.2. At pH 7.0 it displays sigmoidal kinetics with respect to fructose 6-phosphate concentration but its co-operative behaviour is very dependent on pH, protein concentration and the concentration of MgATP. MgGTP and MgITP can replace MgATP as phosphate donors but, unlike MgATP, these nucleotides do not cause significant inhibition. Mn2+ and Co2+ (as the metal ion-ATP complexes) act as cofactors and in the free form are far more inhibitory than free Mg2+. The spleen enzyme responds to a wide variety of potential effector molecules: ADP, AMP, cyclic AMP, aspartate, NH4+, fructose 6-phosphate, fructose 1,6-diphosphate and Pi all act as either activators or protectors, whereas Mg-ATP, Mg2+, citrate, phosphoenol-pyruvate and the phosphoglucerates are inhibitors.", "contents": "The purification and properties of pig spleen phosphofructokinase. Pig spleen phosphofructokinase has been purified 800-fold with a yield of 17%. Two isoenzymes that appear to be kinetically identical can be separated by DEAE-cellulose column chromatography. In common with the enzyme from other mammalian sources, the spleen enzyme has a pH optimum of 8.2. At pH 7.0 it displays sigmoidal kinetics with respect to fructose 6-phosphate concentration but its co-operative behaviour is very dependent on pH, protein concentration and the concentration of MgATP. MgGTP and MgITP can replace MgATP as phosphate donors but, unlike MgATP, these nucleotides do not cause significant inhibition. Mn2+ and Co2+ (as the metal ion-ATP complexes) act as cofactors and in the free form are far more inhibitory than free Mg2+. The spleen enzyme responds to a wide variety of potential effector molecules: ADP, AMP, cyclic AMP, aspartate, NH4+, fructose 6-phosphate, fructose 1,6-diphosphate and Pi all act as either activators or protectors, whereas Mg-ATP, Mg2+, citrate, phosphoenol-pyruvate and the phosphoglucerates are inhibitors."}
{"id": "PMID:3167", "title": "The effect of disulfiram on the aldehyde dehydrogenases of sheep liver.", "content": "1. The effect of disulfiram on the activity of the cytoplasmic and mitochondrial aldehyde dehydrogenases of sheep liver was studied. 2. Disulfiram causes an immediate inhibition of the enzyme reaction. The effect on the cytoplasmic enzyme is much greater than on the mitochondrial enzyme. 3. In both cases, the initial partial inhibition is followed by a gradual irreversible loss of activity. 4. The pH-rate profile of the inactivation of the mitochondrial enzyme by disulfiram and the pH-dependence of the maximum velocity of the enzyme-catalysed reaction are both consistent with the involvement of a thiol group. 5. Excess of 2-mercaptoethanol or GSH abolishes the effect of disulfiram. However, equimolar amounts of either of these reagents and disulfiram cause an effect greater than does disulfiram alone. It was shown that the mixed disulphide, Et2N-CS-SS-CH2-CH2OH, strongly inhibits aldehyde dehydrogenase. 6. The inhibitory effect of diethyldithiocarbamate in vitro is due mainly to contamination by disulfiram.", "contents": "The effect of disulfiram on the aldehyde dehydrogenases of sheep liver. 1. The effect of disulfiram on the activity of the cytoplasmic and mitochondrial aldehyde dehydrogenases of sheep liver was studied. 2. Disulfiram causes an immediate inhibition of the enzyme reaction. The effect on the cytoplasmic enzyme is much greater than on the mitochondrial enzyme. 3. In both cases, the initial partial inhibition is followed by a gradual irreversible loss of activity. 4. The pH-rate profile of the inactivation of the mitochondrial enzyme by disulfiram and the pH-dependence of the maximum velocity of the enzyme-catalysed reaction are both consistent with the involvement of a thiol group. 5. Excess of 2-mercaptoethanol or GSH abolishes the effect of disulfiram. However, equimolar amounts of either of these reagents and disulfiram cause an effect greater than does disulfiram alone. It was shown that the mixed disulphide, Et2N-CS-SS-CH2-CH2OH, strongly inhibits aldehyde dehydrogenase. 6. The inhibitory effect of diethyldithiocarbamate in vitro is due mainly to contamination by disulfiram."}
{"id": "PMID:3168", "title": "A reporter group delivery system with both absolute and selective specificity for thiol groups and an improved fluorescent probe containing the 7-nitrobenzo-2-oxa-1,3-diazole moiety.", "content": "1. 4-(N-2-Aminoethyl2'-pyridyl disulphide)-7-nitrobenzo-2-oxa-1,3-diazole (compound I) was synthesized and evaluated as a fluorescent labelling reagent for thiol groups. 2. The design of compound (I) as one example of a general type of reporter group delivery reagent (2-pyridyl-S-S-X, where X contains an environmentally sensitive spectroscopic probe) is discussed. 3. The electronic absorption spectrum of compound (I) was determined over a wide range of pH and the spectral changes that accompany its reaction with low-molecular-weight thiols, e.g. L-cysteine, and with papain (EC 3.4.22.2) and bovine serum albumin are discussed. 4. A new value of epsilon343 for 2-thiopyridone (Py-2-SH) was determined as 8.08 X 10(3) +/- 0.08 X 10(3)M-1-cm-1. 5. Spectral analysis of the reactions of compound (I) with L-cysteine and with papain (in the pH range 3.5-8.0) showed that even under equimolar conditions the reaction (thiol-disulphide interchange to release Py-2-SH) is essentially stoicheimoetric and probably proceeds by specific attack at the sulphur atom distal from the pyridyl ring of compound (I). 6. The fluorescence-emission spectra of compound (I) and of the products of its reaction with papain and with ficin (EC 3.4.22.3) were determined. Compound (I) is highly fluorescent in aqueous solution. Excitation within the intense visible absorption band (lambda max. 481 nm, epsilon max. 2.52 X 10(4)M-1-cm-1) provides green fluorescence with an emission maximum at 540 nm. Both papain and ficin labelled by reaction with compound (I) are characterized by fluorescence-emission maxima (535 nm and 530 nm respectively) of even higher intensity. The fluorescence emission of the product of the reaction of papain with compound (I) was shown to be 25 times more intense than that of the product of the reaction of papain with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride). 7. The second-order rate constants (k2) for the reactions of compound (I) and of Nbd chloride with GSH, papain, albumin, ficin, 2-benzimidazolylmethanethiol and 2-benzimidazolylethanethiol were determined at 25.0 degrees C and various pH values. At pH4 the values of k2(compound I)/k2(Nbd chloride) are: GSH, 288; albumin, 36; papain 3 X 10(3); ficin, 3 X 10(4). 8. The pH-k2 profiles for the reactions of compound (I) and of Nbd chloride with the two 2-benzimidazolylalkanethiols were determined. Of the four profiles only that for the reaction of compound (I) with 2-benzimidazolylmethanethiol is characterized by a striking rate maximum in acidic media.", "contents": "A reporter group delivery system with both absolute and selective specificity for thiol groups and an improved fluorescent probe containing the 7-nitrobenzo-2-oxa-1,3-diazole moiety. 1. 4-(N-2-Aminoethyl2'-pyridyl disulphide)-7-nitrobenzo-2-oxa-1,3-diazole (compound I) was synthesized and evaluated as a fluorescent labelling reagent for thiol groups. 2. The design of compound (I) as one example of a general type of reporter group delivery reagent (2-pyridyl-S-S-X, where X contains an environmentally sensitive spectroscopic probe) is discussed. 3. The electronic absorption spectrum of compound (I) was determined over a wide range of pH and the spectral changes that accompany its reaction with low-molecular-weight thiols, e.g. L-cysteine, and with papain (EC 3.4.22.2) and bovine serum albumin are discussed. 4. A new value of epsilon343 for 2-thiopyridone (Py-2-SH) was determined as 8.08 X 10(3) +/- 0.08 X 10(3)M-1-cm-1. 5. Spectral analysis of the reactions of compound (I) with L-cysteine and with papain (in the pH range 3.5-8.0) showed that even under equimolar conditions the reaction (thiol-disulphide interchange to release Py-2-SH) is essentially stoicheimoetric and probably proceeds by specific attack at the sulphur atom distal from the pyridyl ring of compound (I). 6. The fluorescence-emission spectra of compound (I) and of the products of its reaction with papain and with ficin (EC 3.4.22.3) were determined. Compound (I) is highly fluorescent in aqueous solution. Excitation within the intense visible absorption band (lambda max. 481 nm, epsilon max. 2.52 X 10(4)M-1-cm-1) provides green fluorescence with an emission maximum at 540 nm. Both papain and ficin labelled by reaction with compound (I) are characterized by fluorescence-emission maxima (535 nm and 530 nm respectively) of even higher intensity. The fluorescence emission of the product of the reaction of papain with compound (I) was shown to be 25 times more intense than that of the product of the reaction of papain with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride). 7. The second-order rate constants (k2) for the reactions of compound (I) and of Nbd chloride with GSH, papain, albumin, ficin, 2-benzimidazolylmethanethiol and 2-benzimidazolylethanethiol were determined at 25.0 degrees C and various pH values. At pH4 the values of k2(compound I)/k2(Nbd chloride) are: GSH, 288; albumin, 36; papain 3 X 10(3); ficin, 3 X 10(4). 8. The pH-k2 profiles for the reactions of compound (I) and of Nbd chloride with the two 2-benzimidazolylalkanethiols were determined. Of the four profiles only that for the reaction of compound (I) with 2-benzimidazolylmethanethiol is characterized by a striking rate maximum in acidic media."}
{"id": "PMID:3169", "title": "Differential effects of temperature on a membrane adenosine triphosphatase and associated phosphatase.", "content": "Arrhenius plots of a membrane (Na+ + K+)-dependent ATPase (adenosine triphosphatase) activity showed characteristic discontinuities, whereas those of the associated K+-dependent phosphatase activity did not. These findings support the contention that the phosphatase activity does not depend on phospholipid in the same way as does the ATPase activity.", "contents": "Differential effects of temperature on a membrane adenosine triphosphatase and associated phosphatase. Arrhenius plots of a membrane (Na+ + K+)-dependent ATPase (adenosine triphosphatase) activity showed characteristic discontinuities, whereas those of the associated K+-dependent phosphatase activity did not. These findings support the contention that the phosphatase activity does not depend on phospholipid in the same way as does the ATPase activity."}
{"id": "PMID:3170", "title": "The action of chelating agents on human liver aldehyde dehydrogenase.", "content": "Human liver aldehyde dehydrogenase was inhibited by aromatic chelating agents. However, structurally related compounds with much lower metal-complexing ability displayed affinities for enzyme essentially equal to those of their respective chelating analogues. Inhibition was competitive with respect to the coenzyme. It is suggested that hydrophobic interactions between the inhibitors and the coenzyme-binding site of the enzyme are responsible for the observed effects on activity.", "contents": "The action of chelating agents on human liver aldehyde dehydrogenase. Human liver aldehyde dehydrogenase was inhibited by aromatic chelating agents. However, structurally related compounds with much lower metal-complexing ability displayed affinities for enzyme essentially equal to those of their respective chelating analogues. Inhibition was competitive with respect to the coenzyme. It is suggested that hydrophobic interactions between the inhibitors and the coenzyme-binding site of the enzyme are responsible for the observed effects on activity."}
{"id": "PMID:3171", "title": "An improved assay for bacterial methane mono-oxygenase: some properties of the enzyme from Methylomonas methanica.", "content": "Extracts of Methylomonas methanica catalyse the O2-and NAD(P)H-dependent disappearance of bromomethane. The activity is unstable at 2 degrees C but is stable at --70 degrees C for several weeks. Bromomethane mono-oxygenase is particulate and is inhibited by metal-binding reagents, by compounds SKF 525A and Lilly 53325, by some metal ions and by acetylene. Evidence is presented that indicates that bromomethane mono-oxygenase is the enzyme responsible for methane oxidation in vivo.", "contents": "An improved assay for bacterial methane mono-oxygenase: some properties of the enzyme from Methylomonas methanica. Extracts of Methylomonas methanica catalyse the O2-and NAD(P)H-dependent disappearance of bromomethane. The activity is unstable at 2 degrees C but is stable at --70 degrees C for several weeks. Bromomethane mono-oxygenase is particulate and is inhibited by metal-binding reagents, by compounds SKF 525A and Lilly 53325, by some metal ions and by acetylene. Evidence is presented that indicates that bromomethane mono-oxygenase is the enzyme responsible for methane oxidation in vivo."}
{"id": "PMID:3172", "title": "Iron oxidation and transferrin formation by phosvitin.", "content": "The catalytic activity of phosvitin in Fe(II) oxidation and the addition of iron to transferrin were studied under various conditions. It was concluded that the Fe(II) oxidized by phosvitin would bind to apotransferrin, although an appreciable fraction of Fe(III) remained bound to phosvitin. Fe(III) also migrated from phosvitin to apotransferrin. This reaction was first-order with respect to Fe(III)-phosvitin concentration with a half-time (t1/2) of 10 min, and a first-order rate constant, k=0.069min-1, in 700 muM-phosphate buffer, pH 7.2, at 30 degrees C. The catalysis of the oxidation of Fe(III) by phosvitin was proportional to O2 concentration, and is quite different from the relative O2 independence of Fe(II) oxidation as catalysed by ferroxidase. A scheme for the mobilization and transfer of iron in the chicken, including the role of ferroxidase, phosyitin and transferrin, is presented.", "contents": "Iron oxidation and transferrin formation by phosvitin. The catalytic activity of phosvitin in Fe(II) oxidation and the addition of iron to transferrin were studied under various conditions. It was concluded that the Fe(II) oxidized by phosvitin would bind to apotransferrin, although an appreciable fraction of Fe(III) remained bound to phosvitin. Fe(III) also migrated from phosvitin to apotransferrin. This reaction was first-order with respect to Fe(III)-phosvitin concentration with a half-time (t1/2) of 10 min, and a first-order rate constant, k=0.069min-1, in 700 muM-phosphate buffer, pH 7.2, at 30 degrees C. The catalysis of the oxidation of Fe(III) by phosvitin was proportional to O2 concentration, and is quite different from the relative O2 independence of Fe(II) oxidation as catalysed by ferroxidase. A scheme for the mobilization and transfer of iron in the chicken, including the role of ferroxidase, phosyitin and transferrin, is presented."}
{"id": "PMID:3173", "title": "The substrate specificity of thermomycolase, an extracellular serine proteinase from the thermophilic fungus Malbranchea pulchella var. sulfurea.", "content": "The specificity of thermomycolase toward glucagon and the oxidized A and B chains of insulin was investigated. Extensive digestion of glucagon occurred when conducted at pH 7.0 and 45 degrees C for 40 min, whereas hydrolysis of only three peptide bonds occurred at pH 7.0 and 28 degrees C for 5 min. A similar situation was observed for the oxidized B chain of insulin, which exhibited only a single major cleavage after 5 min at 25 degrees C. No well-defined specificity for particular amino acid residues was evident, but ready hydrolysis of peptide bonds occurred within sequences containing non-polar residues. This endoproteinase must therefore possess an extended hydrophobic binding site for polypeptides. Thermomycolase hydrolysed acetylalanylalanylalanine methyl ester and elastin-Congo Red at 22 and 8.5 times the rate of porcine elastase respectively. A limited degradation of native collagen and significant hydrolysis of benzyloxycarbonyl-Gly-Pro-Leu-Gly-Pro were suggestive of some collagenase-like activity. No keratinase activity was apparent.", "contents": "The substrate specificity of thermomycolase, an extracellular serine proteinase from the thermophilic fungus Malbranchea pulchella var. sulfurea. The specificity of thermomycolase toward glucagon and the oxidized A and B chains of insulin was investigated. Extensive digestion of glucagon occurred when conducted at pH 7.0 and 45 degrees C for 40 min, whereas hydrolysis of only three peptide bonds occurred at pH 7.0 and 28 degrees C for 5 min. A similar situation was observed for the oxidized B chain of insulin, which exhibited only a single major cleavage after 5 min at 25 degrees C. No well-defined specificity for particular amino acid residues was evident, but ready hydrolysis of peptide bonds occurred within sequences containing non-polar residues. This endoproteinase must therefore possess an extended hydrophobic binding site for polypeptides. Thermomycolase hydrolysed acetylalanylalanylalanine methyl ester and elastin-Congo Red at 22 and 8.5 times the rate of porcine elastase respectively. A limited degradation of native collagen and significant hydrolysis of benzyloxycarbonyl-Gly-Pro-Leu-Gly-Pro were suggestive of some collagenase-like activity. No keratinase activity was apparent."}
{"id": "PMID:3174", "title": "Stimulation of rat liver beta-galactosidase activity by ions.", "content": "1.  The p-nitrophenyl beta-D-galactosidase asctivity in rat liver homogenates of lysosome-rich fractions was shown to be markedly affected by the ionic composition of the medium.  A stimulation of the reaction rate at pH 5 was produced by most of the salts tested, which contained anions such as acetate, SO4(2-) and Cl-, and cations such as Na+, K= and Mg2+.  The most pronounced effect was observed with MgCl2.  Only potassium glutamate was inhibitory. 2. Five peaks of beta-galactosidase activity obtained by DEAE-cellulose chromatography were equally sensitive to changes in the ionic composition of the medium.  In the presence of added NaC1, the whole rate-pH curve was displaced towards higher pH values, the optimum being shifted from 2.0-2.5 to 3.5.  The stimulation at pH 5.0 appeared to be mainly due to changes in Vmax., whereas the apparent Km was slightly modified. 3. Unlike the total, the free beta-galactosidase activity remained unchanged or even declined when KC1 was added to the reaction medium.", "contents": "Stimulation of rat liver beta-galactosidase activity by ions. 1.  The p-nitrophenyl beta-D-galactosidase asctivity in rat liver homogenates of lysosome-rich fractions was shown to be markedly affected by the ionic composition of the medium.  A stimulation of the reaction rate at pH 5 was produced by most of the salts tested, which contained anions such as acetate, SO4(2-) and Cl-, and cations such as Na+, K= and Mg2+.  The most pronounced effect was observed with MgCl2.  Only potassium glutamate was inhibitory. 2. Five peaks of beta-galactosidase activity obtained by DEAE-cellulose chromatography were equally sensitive to changes in the ionic composition of the medium.  In the presence of added NaC1, the whole rate-pH curve was displaced towards higher pH values, the optimum being shifted from 2.0-2.5 to 3.5.  The stimulation at pH 5.0 appeared to be mainly due to changes in Vmax., whereas the apparent Km was slightly modified. 3. Unlike the total, the free beta-galactosidase activity remained unchanged or even declined when KC1 was added to the reaction medium."}
{"id": "PMID:3175", "title": "Pig heart lactate dehydrogenase. Binding of pyruvate and the interconversion of pyruvate-containing ternary complexes.", "content": "1. Lactate oxidation catalysed by pig heart lactate dehydrogenase was studied in the presence of inhibitory concentrations of pyruvate. Experimental results show the presence of an intermediate which occurs immediately after the hydride transfer step, but before the dissociation of pyruvate and the H+ produced by the reaction. The rate constant for pyruvate dissociation and the dissociation constant for pyruvate from the ternary complex differ from those obtained in pyruvate reduction experiments. 2. In single-turnover pyruvate reduction by pig heart lactate dehydrogenase at pH8.0 pyruvate can bind to the enzyme before a H+ is taken up, and the subsequent uptake of a H+ is governed by a step that is also rate-limiting for single-turnover and steady-state NADH oxidation. 3. Observation of various intermediates in the single-turnover pyruvate reduction experiments has made it possible to determine separately the dissociation constant and Km value for pyruvate at pH8.0, and also the catalytic turnover rate and Km for pyruvate under first-order conditions at different pH values. 4. Further studies on single-turnover pyruvate reduction carried out in 2H2O, or in water at low temperature, show another step which, under these conditions, is slower than that controlling H+ uptake and rate-limiting for NADH oxidation. A scheme is presented which explains these results.", "contents": "Pig heart lactate dehydrogenase. Binding of pyruvate and the interconversion of pyruvate-containing ternary complexes. 1. Lactate oxidation catalysed by pig heart lactate dehydrogenase was studied in the presence of inhibitory concentrations of pyruvate. Experimental results show the presence of an intermediate which occurs immediately after the hydride transfer step, but before the dissociation of pyruvate and the H+ produced by the reaction. The rate constant for pyruvate dissociation and the dissociation constant for pyruvate from the ternary complex differ from those obtained in pyruvate reduction experiments. 2. In single-turnover pyruvate reduction by pig heart lactate dehydrogenase at pH8.0 pyruvate can bind to the enzyme before a H+ is taken up, and the subsequent uptake of a H+ is governed by a step that is also rate-limiting for single-turnover and steady-state NADH oxidation. 3. Observation of various intermediates in the single-turnover pyruvate reduction experiments has made it possible to determine separately the dissociation constant and Km value for pyruvate at pH8.0, and also the catalytic turnover rate and Km for pyruvate under first-order conditions at different pH values. 4. Further studies on single-turnover pyruvate reduction carried out in 2H2O, or in water at low temperature, show another step which, under these conditions, is slower than that controlling H+ uptake and rate-limiting for NADH oxidation. A scheme is presented which explains these results."}
{"id": "PMID:3183", "title": "[Analytical profile of purified hexetidine (author's transl)].", "content": "Physico-chemical, spectroscopic (UV, IR, NMR, mass), chromatographic (GLC, TLC) properties and synthesis of 1,3-bis(2-ethylhexyl)-5-amino-5-methyl-hexahydropyrimidine (hexetidine) are reported and discussed. Moreover, the difference between commercial and purified hexetidine is demonstrated.", "contents": "[Analytical profile of purified hexetidine (author's transl)]. Physico-chemical, spectroscopic (UV, IR, NMR, mass), chromatographic (GLC, TLC) properties and synthesis of 1,3-bis(2-ethylhexyl)-5-amino-5-methyl-hexahydropyrimidine (hexetidine) are reported and discussed. Moreover, the difference between commercial and purified hexetidine is demonstrated."}
{"id": "PMID:3184", "title": "[Ditertiary diamine compounds (author's transl)].", "content": "The preparation of ditertiary aliphatic diamines 3 designed as drugs protecting CNS acetylcholinesterase against organophosphate inhibition, is described. Owing to the radicals at the basic nitrogen atoms, these compounds should exist in appreciable amounts both as base and as diammonium ion at biological pH's.", "contents": "[Ditertiary diamine compounds (author's transl)]. The preparation of ditertiary aliphatic diamines 3 designed as drugs protecting CNS acetylcholinesterase against organophosphate inhibition, is described. Owing to the radicals at the basic nitrogen atoms, these compounds should exist in appreciable amounts both as base and as diammonium ion at biological pH's."}
{"id": "PMID:3185", "title": "[Intracellular pH of cardiac muscle after administration of potassium-magnesium-aspartate (author's transl)].", "content": "27 Sprague-Dawley rats were anesthetized with pentobarbital. Artificial ventilation was given by a Starling pump respirator via a tracheal tube. Intracellular pH of cardiac muscle was determined by means of the indirect procedure of measuring the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) in intra- and extracellular spaces (DMO-method). 12 rats were injected i.p. with 0.33 mval potassium-magnesium-aspartate/100 g body weight and 15 rats served as controls. Using a regression analysis, the following relationships were obtained: 1. animals injected with potassium-magnesium-aspartate pHa = --0.75 log PaCO2 + 8.535, PHi = --0.30 log PaCO2 + 7.509, pHi = 0.41 pHa + 4.036; 2. control animals pHa = --0.59 log PaCO2 + 8.308, pHi = --0.27 log PaCO2 + 7.381, pHi = 0.47 pHa + 3.503. At a pCO2 of 40 torr a pHa of 7.33 (7.36) and a pHi of 7.03 (6.95) was obtained. At an arterial pH of 7.40 the pHi was 7.07 (6.98). The results of the control group are written in brackets. -- The experiments demonstrate an increase in the intracellular buffer bases after administration of potassium-magnesium-aspartate. This effect can be recognized by a concomitant increase in the intracellular pH of 0.09 compared to the control group.", "contents": "[Intracellular pH of cardiac muscle after administration of potassium-magnesium-aspartate (author's transl)]. 27 Sprague-Dawley rats were anesthetized with pentobarbital. Artificial ventilation was given by a Starling pump respirator via a tracheal tube. Intracellular pH of cardiac muscle was determined by means of the indirect procedure of measuring the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) in intra- and extracellular spaces (DMO-method). 12 rats were injected i.p. with 0.33 mval potassium-magnesium-aspartate/100 g body weight and 15 rats served as controls. Using a regression analysis, the following relationships were obtained: 1. animals injected with potassium-magnesium-aspartate pHa = --0.75 log PaCO2 + 8.535, PHi = --0.30 log PaCO2 + 7.509, pHi = 0.41 pHa + 4.036; 2. control animals pHa = --0.59 log PaCO2 + 8.308, pHi = --0.27 log PaCO2 + 7.381, pHi = 0.47 pHa + 3.503. At a pCO2 of 40 torr a pHa of 7.33 (7.36) and a pHi of 7.03 (6.95) was obtained. At an arterial pH of 7.40 the pHi was 7.07 (6.98). The results of the control group are written in brackets. -- The experiments demonstrate an increase in the intracellular buffer bases after administration of potassium-magnesium-aspartate. This effect can be recognized by a concomitant increase in the intracellular pH of 0.09 compared to the control group."}
{"id": "PMID:3186", "title": "Pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine), a new antihypertensive agent. III. Action on the secretions of the digestive tract and on the central nervous system, acute toxicity.", "content": "The pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine) a new synthetic derivative of imidazoline are reported in a series of three successive articles. This compound has been shown to possess hypotensive and antihypertensive properties. After i.v. administration, the hypotensive phase was preceded by hypertension related to the potent direct alpha-sympatheticomimetic properties of the product. This pressor response, which was not seen after oral administration, was accompanied by a marked decrease in cardiac output and a significant increase in peripheral vascular resistance. The hypotensive action of the product was due to a drop in cardiac output probably reinforced by a decrease in vasoconstrictor sympathetic tone due to a central action. Whatever the route of administration, tolonidine slowed heart rate independently of blood pressure variations, due essentially to an increase in vagal tone. In studies of diuresis, liquid and salt loss were observed in the cat, not in the dog. At doses which induce a drop in blood pressure tolonidine did not produce a reduction in pilocarpine-induced salivary secretion and only partially inhibited gastric secretion. In the central nervous system, tolonidine produced a sedation which first appeared at doses having an antihypertensive effect but which was only fully apparent with increased doses. A decrease in the release of cerebral amines, serotonin and noradrenaline by tolonidine is proposed. Tolonidine was compared with three other antihypertensive agents: clonidine, which is structurally related, and guanethidine and mecamylamine, which are structurally unrelated and have a different mode of action. A close resemblance of the pharmacological properties of tolonidine and clonidine was established due to the chemical relationship between the two substances.", "contents": "Pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine), a new antihypertensive agent. III. Action on the secretions of the digestive tract and on the central nervous system, acute toxicity. The pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine) a new synthetic derivative of imidazoline are reported in a series of three successive articles. This compound has been shown to possess hypotensive and antihypertensive properties. After i.v. administration, the hypotensive phase was preceded by hypertension related to the potent direct alpha-sympatheticomimetic properties of the product. This pressor response, which was not seen after oral administration, was accompanied by a marked decrease in cardiac output and a significant increase in peripheral vascular resistance. The hypotensive action of the product was due to a drop in cardiac output probably reinforced by a decrease in vasoconstrictor sympathetic tone due to a central action. Whatever the route of administration, tolonidine slowed heart rate independently of blood pressure variations, due essentially to an increase in vagal tone. In studies of diuresis, liquid and salt loss were observed in the cat, not in the dog. At doses which induce a drop in blood pressure tolonidine did not produce a reduction in pilocarpine-induced salivary secretion and only partially inhibited gastric secretion. In the central nervous system, tolonidine produced a sedation which first appeared at doses having an antihypertensive effect but which was only fully apparent with increased doses. A decrease in the release of cerebral amines, serotonin and noradrenaline by tolonidine is proposed. Tolonidine was compared with three other antihypertensive agents: clonidine, which is structurally related, and guanethidine and mecamylamine, which are structurally unrelated and have a different mode of action. A close resemblance of the pharmacological properties of tolonidine and clonidine was established due to the chemical relationship between the two substances."}
{"id": "PMID:3187", "title": "[On the influence of a special preparation of oxytetracycline and sodiumbituminosulfonates on amount and composition of skin surface lipids in acne vulgaris (author's transl)].", "content": "Two groups of 27 and 23 patients with acne vulgaris were first treated for a period of one week with 1 g oxytetracycline a day p.o. In a second treatment period of 6 weeks the first group received 100 mg oxytetracycline a day p.o. and the second group a combination of 100 mg oxytetracycline and 1.2 g sodiumbituminosulfonates a day p.o. In the third treatment period, similarly continued for 6 weeks, the method was reversed. Gastric juice-insoluble preparations were used for the investigation. All criteria for a double-blind study were considered. Amount and composition of the skin surface lipids were analysed before beginning the treatment, at the end of the 2nd and at the end of the 3rd treatment period. The combination of both agents in gastric juice-insoluble preparations suppresses to a great extent the known effects brought about by the substances separately, namely the reduction in free fatty acids and the decrease in the skin surface lipids. The findings also show that the reduction of the free fatty acids was in a limited time observed only in patients treated with 100 mg oxytetracycline a day p.o. if they had been treated in the beginning of this therapy with a higher dosage of tetracycline.", "contents": "[On the influence of a special preparation of oxytetracycline and sodiumbituminosulfonates on amount and composition of skin surface lipids in acne vulgaris (author's transl)]. Two groups of 27 and 23 patients with acne vulgaris were first treated for a period of one week with 1 g oxytetracycline a day p.o. In a second treatment period of 6 weeks the first group received 100 mg oxytetracycline a day p.o. and the second group a combination of 100 mg oxytetracycline and 1.2 g sodiumbituminosulfonates a day p.o. In the third treatment period, similarly continued for 6 weeks, the method was reversed. Gastric juice-insoluble preparations were used for the investigation. All criteria for a double-blind study were considered. Amount and composition of the skin surface lipids were analysed before beginning the treatment, at the end of the 2nd and at the end of the 3rd treatment period. The combination of both agents in gastric juice-insoluble preparations suppresses to a great extent the known effects brought about by the substances separately, namely the reduction in free fatty acids and the decrease in the skin surface lipids. The findings also show that the reduction of the free fatty acids was in a limited time observed only in patients treated with 100 mg oxytetracycline a day p.o. if they had been treated in the beginning of this therapy with a higher dosage of tetracycline."}
{"id": "PMID:3188", "title": "[Influence of ethanol on the in vitro and in vivo drug release from some sustained release tablets (author's transl)].", "content": "The in vitro and in vivo liberation of acetylsalicylic acid from sustained release tablets in presence of ethanol is described. Simultaneous uptake of 120 ml commercial brandy resulted in a faster release of the active substance from the tablets prepared with Eudragit ret-l (PM), as has been proved by urinary excretion data. These results were supported by experiments with a pH-endoaradio transmitter and by radiography.", "contents": "[Influence of ethanol on the in vitro and in vivo drug release from some sustained release tablets (author's transl)]. The in vitro and in vivo liberation of acetylsalicylic acid from sustained release tablets in presence of ethanol is described. Simultaneous uptake of 120 ml commercial brandy resulted in a faster release of the active substance from the tablets prepared with Eudragit ret-l (PM), as has been proved by urinary excretion data. These results were supported by experiments with a pH-endoaradio transmitter and by radiography."}
{"id": "PMID:3192", "title": "Changes in liver function after different types of surgery.", "content": "Liver function tests carried out after minor surgical procedures, under anaesthesia lasting for 1 hr, showed no abnormalities. Tests after body surface operations under the same anaesthetic techniques showed transient derangements. After intra-abdominal procedures, liver dysfunction was more marked, although no patients with evidence of preoperative liver dysfunction or postoperative surgical complications were studied and none received blood transfusions. Measurements of the serum bilirubin concentration showed the most frequent abnormalities, but the pseudocholinesterase concentration decreased progressively after intra-abdominal surgery and b.s.p. retention increased significantly. Serum concentration of intracellular enzymes (LDH, s.g.o.t. and s.g.p.t.) increased within an hour of starting surgery, changes which were probably not related to liver function.", "contents": "Changes in liver function after different types of surgery. Liver function tests carried out after minor surgical procedures, under anaesthesia lasting for 1 hr, showed no abnormalities. Tests after body surface operations under the same anaesthetic techniques showed transient derangements. After intra-abdominal procedures, liver dysfunction was more marked, although no patients with evidence of preoperative liver dysfunction or postoperative surgical complications were studied and none received blood transfusions. Measurements of the serum bilirubin concentration showed the most frequent abnormalities, but the pseudocholinesterase concentration decreased progressively after intra-abdominal surgery and b.s.p. retention increased significantly. Serum concentration of intracellular enzymes (LDH, s.g.o.t. and s.g.p.t.) increased within an hour of starting surgery, changes which were probably not related to liver function."}
{"id": "PMID:3193", "title": "Studies on the energy metabolism in lichen planus.", "content": "Various epidermal enzymes and cofactors were measured in patients with lichen planus and in healthy controls with the aid of Lowry's microtechniques, including enzymatic cycling. The steady-state levels of the nicotinamide adenine dinucleotides NAD and NADP were decreased and this was evident even in areas still free from lesions. The oxidized and reduced portions of NAD were altered indicating changed equilibria of NAD dependent dehydrogenases. Reduced NADP was more tightly controlled at the normal level which is regarded as evidence of an unaltered biosynthetic potential in this disease. In conjunction with earlier data the results indicate a preserved glycolytic and pentose shunt activity while the mitochondria display signs of dysfunction.", "contents": "Studies on the energy metabolism in lichen planus. Various epidermal enzymes and cofactors were measured in patients with lichen planus and in healthy controls with the aid of Lowry's microtechniques, including enzymatic cycling. The steady-state levels of the nicotinamide adenine dinucleotides NAD and NADP were decreased and this was evident even in areas still free from lesions. The oxidized and reduced portions of NAD were altered indicating changed equilibria of NAD dependent dehydrogenases. Reduced NADP was more tightly controlled at the normal level which is regarded as evidence of an unaltered biosynthetic potential in this disease. In conjunction with earlier data the results indicate a preserved glycolytic and pentose shunt activity while the mitochondria display signs of dysfunction."}
{"id": "PMID:3194", "title": "The lichen planus-like eruption after bone marrow transplantation.", "content": "A lichen planus-like eruption was seen in four patients after bone marrow transplantation. The skin and mucous membrane appearance closely mimicked lichen planus. The histopathology was also very similar to lichen planus. The occurrence of a lichen planus-like eruption (LPLE) after an immune basal cell damage related to the graft-versus-host reaction raised the question of the immune nature of this eruption. The correlation found between biological signs of graft-versus-host reaction and the out-break or relapse of the lichen planus-like eruption supports the hypothesis that the skin changes could be a sign of a chronic immune response against recipient epidermis.", "contents": "The lichen planus-like eruption after bone marrow transplantation. A lichen planus-like eruption was seen in four patients after bone marrow transplantation. The skin and mucous membrane appearance closely mimicked lichen planus. The histopathology was also very similar to lichen planus. The occurrence of a lichen planus-like eruption (LPLE) after an immune basal cell damage related to the graft-versus-host reaction raised the question of the immune nature of this eruption. The correlation found between biological signs of graft-versus-host reaction and the out-break or relapse of the lichen planus-like eruption supports the hypothesis that the skin changes could be a sign of a chronic immune response against recipient epidermis."}
{"id": "PMID:3195", "title": "The effect of pH upon human transferrin: selective labelling of the two iron-binding sites.", "content": "The influence of pH changes upon the iron-binding properties of transferrin was investigated in the absence of chelating agents. The effects were demonstrated by spectrophotometry, gel filtration, and by studies of the intermolecular transfer of 59Fe from transferrin to conalbumin. At pH values below 6.7, diferric transferrin readily loses iron. The monoferric molecule, which is relatively resistant to acid dissociation, is preferentially formed. A temporary reduction of pH provides a simple method for selectively attaching iron to one metal-binding site, and allows double isotopic labelling of the transferrin molecule. This technique may permit further investigation of the physiological properties of the two iron-binding sites.", "contents": "The effect of pH upon human transferrin: selective labelling of the two iron-binding sites. The influence of pH changes upon the iron-binding properties of transferrin was investigated in the absence of chelating agents. The effects were demonstrated by spectrophotometry, gel filtration, and by studies of the intermolecular transfer of 59Fe from transferrin to conalbumin. At pH values below 6.7, diferric transferrin readily loses iron. The monoferric molecule, which is relatively resistant to acid dissociation, is preferentially formed. A temporary reduction of pH provides a simple method for selectively attaching iron to one metal-binding site, and allows double isotopic labelling of the transferrin molecule. This technique may permit further investigation of the physiological properties of the two iron-binding sites."}
{"id": "PMID:3196", "title": "The effect of parturition on amniotic fluid lecithin concentration.", "content": "Amniotic fluid lecithin has been measured during the antenatal period and at comparable periods of gestation at the onset of spontaneous labour. Lecithin values were higher in labour, the difference being statistically significant in two of the three groups studied. Lecithin values were also measured serially during induced labour in 14 normal women at term. A significant fall was observed throughout labour. Creatinine levels were measured in the amniotic fluid in five of these patients and showed no significant change.", "contents": "The effect of parturition on amniotic fluid lecithin concentration. Amniotic fluid lecithin has been measured during the antenatal period and at comparable periods of gestation at the onset of spontaneous labour. Lecithin values were higher in labour, the difference being statistically significant in two of the three groups studied. Lecithin values were also measured serially during induced labour in 14 normal women at term. A significant fall was observed throughout labour. Creatinine levels were measured in the amniotic fluid in five of these patients and showed no significant change."}
{"id": "PMID:3197", "title": "The effects of narcotics on fetal acid base status.", "content": "This paper reports two randomized control trials on the effects of nalorphine, pethidine, morphine and heroin on fetal and maternal acid base status. The drugs decreased pH and increased pCO2 in the mother, and decreased pH and base excess in the fetus. The changes in the fetus were independent of the changes in the mother. In equivalent dosages, nalorphine increased maternal pCO2 more than pethidine and morphine. The effects of heroin were found to be greater than that of other drugs, and we suggest that heroin should be avoided where the fetus is already at risk.", "contents": "The effects of narcotics on fetal acid base status. This paper reports two randomized control trials on the effects of nalorphine, pethidine, morphine and heroin on fetal and maternal acid base status. The drugs decreased pH and increased pCO2 in the mother, and decreased pH and base excess in the fetus. The changes in the fetus were independent of the changes in the mother. In equivalent dosages, nalorphine increased maternal pCO2 more than pethidine and morphine. The effects of heroin were found to be greater than that of other drugs, and we suggest that heroin should be avoided where the fetus is already at risk."}
{"id": "PMID:3198", "title": "On the solution conformation of bradykinin and certain fragments.", "content": "A circular dichroism (CD) study of [D-Pro2]- and [D-Pro3]-bradykinin, selected peptide fragments, and the model compound. N-acetyl-L-phenylalaninamide, support our previous conclusion (Biochemistry 12, 3780, 1973) that the positive 221-nm CD band of bradykinin is a composite of bands due to two chromophores, the 217-nm band characteristic of the Phe residues overlying the 223-nm band of the N-terminal sequence, Arg-Pro-Pro. The results also indicate that the 223-nm band of Arg-Pro-Pro is associated with the configuration of the Pro-Pro sequence, Arg-D-Pro-Pro and Arg-Pro-D-Pro virtually being diastereoisomers. Accordingly, the conformation of Arg-Pro-Pro was probed in further detail. Upon increasing the temperature from about 27 to 65 degrees C, Arg-Pro-Pro undergoes a conformational transition characterized by large positive values of deltaHdegrees and deltaSdegrees, which is interpreted to mean that the structure of water and, thus, solute-solvent interactions play a dominant role in determining the conformation of the peptide 13C nuclear magnetic resonance spectroscopy indicates that the effect of lowering the pH on the CD of Arg-Pro-Pro is explicable in terms of hydrogen-bond formation between the carboxyl group and Pro2 carbonyl oxygen at acid pH with concomitant cis to trans isomerization.", "contents": "On the solution conformation of bradykinin and certain fragments. A circular dichroism (CD) study of [D-Pro2]- and [D-Pro3]-bradykinin, selected peptide fragments, and the model compound. N-acetyl-L-phenylalaninamide, support our previous conclusion (Biochemistry 12, 3780, 1973) that the positive 221-nm CD band of bradykinin is a composite of bands due to two chromophores, the 217-nm band characteristic of the Phe residues overlying the 223-nm band of the N-terminal sequence, Arg-Pro-Pro. The results also indicate that the 223-nm band of Arg-Pro-Pro is associated with the configuration of the Pro-Pro sequence, Arg-D-Pro-Pro and Arg-Pro-D-Pro virtually being diastereoisomers. Accordingly, the conformation of Arg-Pro-Pro was probed in further detail. Upon increasing the temperature from about 27 to 65 degrees C, Arg-Pro-Pro undergoes a conformational transition characterized by large positive values of deltaHdegrees and deltaSdegrees, which is interpreted to mean that the structure of water and, thus, solute-solvent interactions play a dominant role in determining the conformation of the peptide 13C nuclear magnetic resonance spectroscopy indicates that the effect of lowering the pH on the CD of Arg-Pro-Pro is explicable in terms of hydrogen-bond formation between the carboxyl group and Pro2 carbonyl oxygen at acid pH with concomitant cis to trans isomerization."}
{"id": "PMID:3199", "title": "The activation of ribulose-1,5-bisphosphate carboxylase by carbon dioxide and magnesium ions. Equilibria, kinetics, a suggested mechanism, and physiological implications.", "content": "Ribulose-1,5-bisphosphate carboxylase was activated by incubation with CO2 and Mg2++, and inactivated upon removal of CO2 and Mg2+ by gel filtration. The activation process involved CO2 rather than HCO3-. The activity of the enzyme was dependent upon the preincubation concentrations of CO2 and Mg2+ and upon the preincubation pH, indicating that activation involved the reversible formation of an equilibrium complex of enzyme-CO2-Mg. The initial rate of activation was linearly dependent upon the CO2 concentration but independent of the Mg2+ concentration. Kinetic analyses indicated that the enzyme reacted first with CO2 in a rate-determining and reversible step, followed by a rapid reaction with Mg2+ to form an active ternary complex (see eq 1 in text). The pseudo-first order rate constant, kobsd, for the activation process at constant pH was derived: kobsd=k1[CO2] + (k2k4/k3[Mg2+]). Experimentally, kobsd was shown to be linearly dependent upon the CO2 concentration and inversely dependent upon the Mg2+ concentration. The activity of the enzyme after preincubation to equilibrium at constant concentrations of CO2 and Mg2+ increased as the preincubation pH was raised, indicating that CO2 reacted with an enzyme group whose pK was distinctly alkaline. It is proposed that the activation of ribulose-1, 5-biphosphate carboxylane involves the formation of a carbamate.", "contents": "The activation of ribulose-1,5-bisphosphate carboxylase by carbon dioxide and magnesium ions. Equilibria, kinetics, a suggested mechanism, and physiological implications. Ribulose-1,5-bisphosphate carboxylase was activated by incubation with CO2 and Mg2++, and inactivated upon removal of CO2 and Mg2+ by gel filtration. The activation process involved CO2 rather than HCO3-. The activity of the enzyme was dependent upon the preincubation concentrations of CO2 and Mg2+ and upon the preincubation pH, indicating that activation involved the reversible formation of an equilibrium complex of enzyme-CO2-Mg. The initial rate of activation was linearly dependent upon the CO2 concentration but independent of the Mg2+ concentration. Kinetic analyses indicated that the enzyme reacted first with CO2 in a rate-determining and reversible step, followed by a rapid reaction with Mg2+ to form an active ternary complex (see eq 1 in text). The pseudo-first order rate constant, kobsd, for the activation process at constant pH was derived: kobsd=k1[CO2] + (k2k4/k3[Mg2+]). Experimentally, kobsd was shown to be linearly dependent upon the CO2 concentration and inversely dependent upon the Mg2+ concentration. The activity of the enzyme after preincubation to equilibrium at constant concentrations of CO2 and Mg2+ increased as the preincubation pH was raised, indicating that CO2 reacted with an enzyme group whose pK was distinctly alkaline. It is proposed that the activation of ribulose-1, 5-biphosphate carboxylane involves the formation of a carbamate."}
{"id": "PMID:3200", "title": "Manganese (II) and substrate interaction with unadenylylated glutamine synthetase (Escherichia coli w). II. Electron paramagnetic resonance and nuclear magnetic resonance studies of enzyme-bound manganese(II) with substrates and a potential transition-state analogue, methionine sulfoximine.", "content": "The enhancement of the longitudinal proton relaxation rate of solvent water protons which occurs when Mn(II) is bound to the \"tight\" metal ion site of unadenylylated glutamine synthetase (GS) was used to determine the binding constant of L-methionine (SR)-sulfoximine to GS-Mn(II) complexes. The binary enhancement for GS-Mn(II) is 22 at 24 MHz, 25 degrees C. The enhancement is lowered in the presence of the sulfoximine and the computed dissociation constant is 30 muM with epsilont, the enhancement for the ternary complex, equal to 3.0. Titration curves for the sulfoximine were also obtained in the presence of Mg-ADP, Mg-ADP plus Pi, and Mg-ATP. The dissociation constants were 9, 5, and 0.8 muM, respectively. The progressive tightening of the dissociation constants is symptomatic of conformational changes at the active site as the total subsite occupied by ATP is filled. The number of rapidly exchanging water molecules drops from 2 to approximately 0.1 when saturating concentrations of L-methionine (SR)-sulfoximine and nucleotide are present. The kinetically determined KI value of approximately 4 muM for the sulfoximine is about three orders of magnitude tighter than thee Km' value of approximately 3 mM for L-glutamate. The previously mentioned dissociation constants obtained by enhancement titrations are also orders of magnitude tighter than Km'. These data suggest that L-methionine (SR)-sulfoximine is a \"transition-state\" analogue for the glutamine synthetase reaction. ...", "contents": "Manganese (II) and substrate interaction with unadenylylated glutamine synthetase (Escherichia coli w). II. Electron paramagnetic resonance and nuclear magnetic resonance studies of enzyme-bound manganese(II) with substrates and a potential transition-state analogue, methionine sulfoximine. The enhancement of the longitudinal proton relaxation rate of solvent water protons which occurs when Mn(II) is bound to the \"tight\" metal ion site of unadenylylated glutamine synthetase (GS) was used to determine the binding constant of L-methionine (SR)-sulfoximine to GS-Mn(II) complexes. The binary enhancement for GS-Mn(II) is 22 at 24 MHz, 25 degrees C. The enhancement is lowered in the presence of the sulfoximine and the computed dissociation constant is 30 muM with epsilont, the enhancement for the ternary complex, equal to 3.0. Titration curves for the sulfoximine were also obtained in the presence of Mg-ADP, Mg-ADP plus Pi, and Mg-ATP. The dissociation constants were 9, 5, and 0.8 muM, respectively. The progressive tightening of the dissociation constants is symptomatic of conformational changes at the active site as the total subsite occupied by ATP is filled. The number of rapidly exchanging water molecules drops from 2 to approximately 0.1 when saturating concentrations of L-methionine (SR)-sulfoximine and nucleotide are present. The kinetically determined KI value of approximately 4 muM for the sulfoximine is about three orders of magnitude tighter than thee Km' value of approximately 3 mM for L-glutamate. The previously mentioned dissociation constants obtained by enhancement titrations are also orders of magnitude tighter than Km'. These data suggest that L-methionine (SR)-sulfoximine is a \"transition-state\" analogue for the glutamine synthetase reaction. ..."}
{"id": "PMID:3201", "title": "The interaction of borate and sulfite with pyridine nucleotides.", "content": "The kinetics and equilibria of the borate interaction at ribose with NAD+ and NMN+ have been measured using as a chromophoric probe the perturbation effect borate has on the addition of sulfite to the 4 position of the nicotinamide ring. NAD+ and NMN+ have more favorable borate association constants than do their corresponding sulfite addition complexes. The rate of interaction of the ribose moiety with borate at low borate buffer concentration is dependent on the concentration of both borate and boric acid. At high borate concentration the rate becomes independent of borate concentration, indicating the existence of a two-step process for the interaction of NAD-sulfite with borate with a change of rate-determining step from the interaction of the ribose hydroxyl group with borate at low borate to an elimination of sulfite at high borate concentration. A linear free energy relationship with a slope of 0.94 describes an increased reactivity of the nucleotide for sulfite as the affinity of the nucleotide for sulfite increases.", "contents": "The interaction of borate and sulfite with pyridine nucleotides. The kinetics and equilibria of the borate interaction at ribose with NAD+ and NMN+ have been measured using as a chromophoric probe the perturbation effect borate has on the addition of sulfite to the 4 position of the nicotinamide ring. NAD+ and NMN+ have more favorable borate association constants than do their corresponding sulfite addition complexes. The rate of interaction of the ribose moiety with borate at low borate buffer concentration is dependent on the concentration of both borate and boric acid. At high borate concentration the rate becomes independent of borate concentration, indicating the existence of a two-step process for the interaction of NAD-sulfite with borate with a change of rate-determining step from the interaction of the ribose hydroxyl group with borate at low borate to an elimination of sulfite at high borate concentration. A linear free energy relationship with a slope of 0.94 describes an increased reactivity of the nucleotide for sulfite as the affinity of the nucleotide for sulfite increases."}
{"id": "PMID:3202", "title": "Oxidation of corticosteroids to steroidal-21-oic acids by human liver enzyme.", "content": "An enzyme that oxidizes corticosteroids to acidic metabolites has been purified from postmortem human liver. The most rapidly oxidized substrate was 11-deoxycorticosterone (DOC). Other corticosteroids were oxidized at rates that were 10% or less of DOC. The products of DOC oxidation were 3, 20-dioxopregn-4-en-21-oic acid and 20-hydroxy-3-oxopregn-4-en-21-oic acid. The 20-keto acid was the predominant metabolite in all enzyme preparations. Keto acid and hydroxy acid were not interconverted. Enzyme activity was assayed by measuring the transfer of tritium from [21-3H]DOC to water. The enzyme is yellow, and has spectral maxima at 278 and 405 nm. Inhibition by o-phenanthroline suggests that it may be a metalloenzyme. Molecular weight was estimated at 74 000 +/- 8 000; a pH maximum occurred at pH 8-8.5. This enzyme may participate in the in vivo conversion of corticosteroids to the acidic metabolites that we have described previously (H.L. Bradlow et al. (1973), J. Clin. Endocrinol. Metab. 37, 811).", "contents": "Oxidation of corticosteroids to steroidal-21-oic acids by human liver enzyme. An enzyme that oxidizes corticosteroids to acidic metabolites has been purified from postmortem human liver. The most rapidly oxidized substrate was 11-deoxycorticosterone (DOC). Other corticosteroids were oxidized at rates that were 10% or less of DOC. The products of DOC oxidation were 3, 20-dioxopregn-4-en-21-oic acid and 20-hydroxy-3-oxopregn-4-en-21-oic acid. The 20-keto acid was the predominant metabolite in all enzyme preparations. Keto acid and hydroxy acid were not interconverted. Enzyme activity was assayed by measuring the transfer of tritium from [21-3H]DOC to water. The enzyme is yellow, and has spectral maxima at 278 and 405 nm. Inhibition by o-phenanthroline suggests that it may be a metalloenzyme. Molecular weight was estimated at 74 000 +/- 8 000; a pH maximum occurred at pH 8-8.5. This enzyme may participate in the in vivo conversion of corticosteroids to the acidic metabolites that we have described previously (H.L. Bradlow et al. (1973), J. Clin. Endocrinol. Metab. 37, 811)."}
{"id": "PMID:3203", "title": "A spectrophotometric and fluorimetric study of alkaline transitions of Euglena cytochrome c 552.", "content": "The behavior of the photosynthetic cytochrome c552 upon titration with alkali depends on the ionic composition of the medium. In water the disappearance of the 695-nm band, indicating the displacement of the methionine ligand, as well as a remarkable tryptophan fluorescense enhancement, follow a single proton titration curve with pK of 10.0 and n=1.0. The product is a low spin type protein. In salt-containing media two successive steps are observed: in the first one, completed at about pH 10.3, a high-spin form of cytochrome c 552 is obtained and relatively small fluorescence enhancement is detected. In the second step, more profound fluorometric changes occur, while the material reverts to its low-spin form. Addition of salts to an alkaline solution of cytochrome c 552 in water results in the formation of a 600-nm high-spin band with a concomitant quenching of tryptophan fluorescence. The results imply that at high pH unfolding of the molecule is evident only when the low-spin product is obtained. In the high-spin alkaline form, the methionine ligand is probably displaced from iron coordination by hydroxyl ions, while in the low-spin alkaline form methionine may be replaced by a lysyl residue of the cytochrome c 552 protein. The results imply that the lysyl residue is available for coordination in salt solutions at a higher pH than in water.", "contents": "A spectrophotometric and fluorimetric study of alkaline transitions of Euglena cytochrome c 552. The behavior of the photosynthetic cytochrome c552 upon titration with alkali depends on the ionic composition of the medium. In water the disappearance of the 695-nm band, indicating the displacement of the methionine ligand, as well as a remarkable tryptophan fluorescense enhancement, follow a single proton titration curve with pK of 10.0 and n=1.0. The product is a low spin type protein. In salt-containing media two successive steps are observed: in the first one, completed at about pH 10.3, a high-spin form of cytochrome c 552 is obtained and relatively small fluorescence enhancement is detected. In the second step, more profound fluorometric changes occur, while the material reverts to its low-spin form. Addition of salts to an alkaline solution of cytochrome c 552 in water results in the formation of a 600-nm high-spin band with a concomitant quenching of tryptophan fluorescence. The results imply that at high pH unfolding of the molecule is evident only when the low-spin product is obtained. In the high-spin alkaline form, the methionine ligand is probably displaced from iron coordination by hydroxyl ions, while in the low-spin alkaline form methionine may be replaced by a lysyl residue of the cytochrome c 552 protein. The results imply that the lysyl residue is available for coordination in salt solutions at a higher pH than in water."}
{"id": "PMID:3204", "title": "Synthetic flavinyl peptides related to the active site of mitochondrial monoamine oxidase II. Fluorescence properties.", "content": "The fluorescence properties of various 8alpha-sulfur-linked flavinyl peptides and related flavin analogues were investigated as the pH solvent, temperature, and flavin concentration were varied. Substitution in the 8alpha position by a thioether-linked peptide brings about a marked quenching of fluorescence (up to 98% in water), a slight bathochromic shift and broadening of the fluorescence emission spectra, and a slight decrease in the fluorescence lifetimes. Oxidation of the thioether function to a sulfone partially releases this fluorescence quenching without further changes in the fluorescence emission spectra. The primary effect on the fluorescence intensity is due to an interaction between the nonbonding electrons of the thioether, the hydrogen-bonding, polar solvent, and the isoalloxazine ring. Dissolving these flavinyl peptides in nonaqueous solvents increases the fluorescence intensity as much as  20-fold. A secondary effect on flavinyl fluorescence can be attributed to a collisional quenching by the vicinal tyrosyl residue within tyrosine-containing flavinyl peptides. The fluorescence properties provide further confirmation of the identity of the synthetic and naturally obtained flavinyl peptides and of the interaction between the free-hydroxyl functions of the ribityl side chain and the thioether.", "contents": "Synthetic flavinyl peptides related to the active site of mitochondrial monoamine oxidase II. Fluorescence properties. The fluorescence properties of various 8alpha-sulfur-linked flavinyl peptides and related flavin analogues were investigated as the pH solvent, temperature, and flavin concentration were varied. Substitution in the 8alpha position by a thioether-linked peptide brings about a marked quenching of fluorescence (up to 98% in water), a slight bathochromic shift and broadening of the fluorescence emission spectra, and a slight decrease in the fluorescence lifetimes. Oxidation of the thioether function to a sulfone partially releases this fluorescence quenching without further changes in the fluorescence emission spectra. The primary effect on the fluorescence intensity is due to an interaction between the nonbonding electrons of the thioether, the hydrogen-bonding, polar solvent, and the isoalloxazine ring. Dissolving these flavinyl peptides in nonaqueous solvents increases the fluorescence intensity as much as  20-fold. A secondary effect on flavinyl fluorescence can be attributed to a collisional quenching by the vicinal tyrosyl residue within tyrosine-containing flavinyl peptides. The fluorescence properties provide further confirmation of the identity of the synthetic and naturally obtained flavinyl peptides and of the interaction between the free-hydroxyl functions of the ribityl side chain and the thioether."}
{"id": "PMID:3205", "title": "High molecular weight deoxyribonucleic acid polymerase from crown gall tumor cells of periwinkle (Vinca rosea).", "content": "A high molecular weight (6 S) plant DNA polymerase from axenic Vinca rosea tissue culture cells has been purified 2200-fold and characterized. The enzyme has a molecular weight of 105 000 (+/-5000). Sodium dodecyl sulfate-acrylamide gel electrophoresis of the purified enzyme yields polypeptide subunits having molecular weights of 70 000 and 34 000. The purified enzyme has a pH optimum of 7.5; a cation requirement optimum of 6 mM Mg2+ or 0.5 mM Mn2+; an apparent requirement for Zn2+; a Km of 1 muM for dTTP; and a 3.5-fold stimulation by 50 mM KCl. The enzyme is sensitive to N-ethylmaleimide (1 mM), heparin (0.1 muM), ethanol (5%), pyrophosphate (0.05 muM), and o-phenanthroline (0.1 mM) but is insensitive to rifamycin. Denatured DNA is found to be the best natural template, and only negligible activity can be demonstrated with the ribopolymer templates poly(dT)n-poly(rA)n and p(dT)10-poly(rA)n. In addition to the polymerization reaction, the enzyme catalyzes a pyrophosphate exchange reaction. Antibody to calf thymus 6-8S DNA polymerase does not inhibit DNA polymerase from Vinca rosea, suggesting no antigenic relationships between the mammalian and plant enzymes.", "contents": "High molecular weight deoxyribonucleic acid polymerase from crown gall tumor cells of periwinkle (Vinca rosea). A high molecular weight (6 S) plant DNA polymerase from axenic Vinca rosea tissue culture cells has been purified 2200-fold and characterized. The enzyme has a molecular weight of 105 000 (+/-5000). Sodium dodecyl sulfate-acrylamide gel electrophoresis of the purified enzyme yields polypeptide subunits having molecular weights of 70 000 and 34 000. The purified enzyme has a pH optimum of 7.5; a cation requirement optimum of 6 mM Mg2+ or 0.5 mM Mn2+; an apparent requirement for Zn2+; a Km of 1 muM for dTTP; and a 3.5-fold stimulation by 50 mM KCl. The enzyme is sensitive to N-ethylmaleimide (1 mM), heparin (0.1 muM), ethanol (5%), pyrophosphate (0.05 muM), and o-phenanthroline (0.1 mM) but is insensitive to rifamycin. Denatured DNA is found to be the best natural template, and only negligible activity can be demonstrated with the ribopolymer templates poly(dT)n-poly(rA)n and p(dT)10-poly(rA)n. In addition to the polymerization reaction, the enzyme catalyzes a pyrophosphate exchange reaction. Antibody to calf thymus 6-8S DNA polymerase does not inhibit DNA polymerase from Vinca rosea, suggesting no antigenic relationships between the mammalian and plant enzymes."}
{"id": "PMID:3206", "title": "Preparation, characterization, and chemical properties of the flavin coenzyme analogues 5-deazariboflavin, 5-deazariboflavin 5'-phosphate, and 5-deazariboflavin 5'-diphosphate, 5'leads to5'-adenosine ester.", "content": "In order to facilitate interpretation of the deazaisoalloxazine system as a valid mechanistic probe of flavoenzyme catalysis, we have examined some of the fundamental chemical properties of this system. The enzymatic synthesis, on a micromole scale, of the flavin coenzyme analogues 5-deazariboflavin 5'-phosphate (deazaFMN) and 5-deazariboflavin 5'-diphosphate, 5' leads to 5'adenosine ester (deazaFAD) has been achieved. This latter synthesis is accomplished with a partially purified FAD synthetase complex (from Brevibacterium ammoniagenes), containing both phosphorylating and adenylylating activities, allowing direct conversion of the riboflavin analogue to the flavin adenine dinucleotide level. The structure of the reduced deazaflavin resulting from enzymatic and chemical reduction is established as the 1,5-dihydrodeazaflavin by proton magnetic resonance. Similarly, the C-5 position of the deazaflavins is demonstrated to be the locus for hydrogen transfer in deazaflavin redox reactions. Preparation of 1,5-dihydrodeazaflavins by sodium borohydride reduction stabilized them to autoxidation (t 1/2 approximately 40 h, 22 degrees C) although dihydrodeazaflavins are rapidly oxidized by other electron acceptors, including riboflavin, phenazine methosulfate, methylene blue, and dichlorophenolindophenol. Mixtures of oxidized and reduced deazaflavins undergo a rapid two-electron disproportionation (k = 22 M-1 S-1 0 degrees C), and oxidized deazaflavins form transient covalent adducts with nitroalkane anions at pH less than 5. Generalized methods for the synthesis of isotopically labeled flavin and deazaflavin coenzymes and their purification by adsorptive chromatography are given.", "contents": "Preparation, characterization, and chemical properties of the flavin coenzyme analogues 5-deazariboflavin, 5-deazariboflavin 5'-phosphate, and 5-deazariboflavin 5'-diphosphate, 5'leads to5'-adenosine ester. In order to facilitate interpretation of the deazaisoalloxazine system as a valid mechanistic probe of flavoenzyme catalysis, we have examined some of the fundamental chemical properties of this system. The enzymatic synthesis, on a micromole scale, of the flavin coenzyme analogues 5-deazariboflavin 5'-phosphate (deazaFMN) and 5-deazariboflavin 5'-diphosphate, 5' leads to 5'adenosine ester (deazaFAD) has been achieved. This latter synthesis is accomplished with a partially purified FAD synthetase complex (from Brevibacterium ammoniagenes), containing both phosphorylating and adenylylating activities, allowing direct conversion of the riboflavin analogue to the flavin adenine dinucleotide level. The structure of the reduced deazaflavin resulting from enzymatic and chemical reduction is established as the 1,5-dihydrodeazaflavin by proton magnetic resonance. Similarly, the C-5 position of the deazaflavins is demonstrated to be the locus for hydrogen transfer in deazaflavin redox reactions. Preparation of 1,5-dihydrodeazaflavins by sodium borohydride reduction stabilized them to autoxidation (t 1/2 approximately 40 h, 22 degrees C) although dihydrodeazaflavins are rapidly oxidized by other electron acceptors, including riboflavin, phenazine methosulfate, methylene blue, and dichlorophenolindophenol. Mixtures of oxidized and reduced deazaflavins undergo a rapid two-electron disproportionation (k = 22 M-1 S-1 0 degrees C), and oxidized deazaflavins form transient covalent adducts with nitroalkane anions at pH less than 5. Generalized methods for the synthesis of isotopically labeled flavin and deazaflavin coenzymes and their purification by adsorptive chromatography are given."}
{"id": "PMID:3207", "title": "Enzyme-catalyzed redox reactions with the flavin analogues 5-deazariboflavin, 5-deazariboflavin 5'-phosphte, and 5-deazariboflavin 5'-diphosphate, 5' leads to 5'-adenosine ester.", "content": "The ability of 5-deazaisoalloxazines to substitute for the isoalloxazine (flavin) coenzyme has been examined with several flavoenzymes. Without exception, the deazaflavin is recognized at the active site and undergoes a redox change in the presence of the specific enzyme substrate. Thus, deazariboflavin is reduced catalytically by NADH in the presence of the Beneckea harveyi NAD(P)H:(flavin) oxidoreductase, the reaction proceeding to an equilibrium with an equilibrium constant near unity. This implies an E0 of -0.310 V for the deazariboflavindihydrodeazariboflavin couple, much lower than that for isoalloxazines. With this enzyme, both riboflavin and deazariboflavin show the same stereospecificity with respect to the pyridine nucleotide, and despite a large difference in Vmax for the two, both have the same rate-determining step (hydrogen transfer). Direct transfer of the hydrogen is seen between the nicotinamide and deazariboflavin in both reaction directions. DeazaFMN reconstituted yeast NADPH: (acceptor) oxidoreductase (Old Yellow Enzyme), and deazaFAD reconstituted D-amino acid:O2 oxidoreductase and Aspergillus niger D-glucose O2 oxidoreductase are all reduced by substrate at approximately 10(-5) the rate of holoenzyme; none are reoxidized by oxygen or any of the tested artificial electron acceptors, though deazaFADH-bound to D-amino acid:O2 oxidoreductase is rapidly oxidized by the imino acid product. Direct hydrogen transfer from substrate to deazaflavin has been demonstrated for both deazaFAD-reconstituted oxidases. These data implicate deazaflavins as a unique probe of flavin catalysis, in that any mechanism for the flavin catalysis must account for the deazaflavin reactivity as well.", "contents": "Enzyme-catalyzed redox reactions with the flavin analogues 5-deazariboflavin, 5-deazariboflavin 5'-phosphte, and 5-deazariboflavin 5'-diphosphate, 5' leads to 5'-adenosine ester. The ability of 5-deazaisoalloxazines to substitute for the isoalloxazine (flavin) coenzyme has been examined with several flavoenzymes. Without exception, the deazaflavin is recognized at the active site and undergoes a redox change in the presence of the specific enzyme substrate. Thus, deazariboflavin is reduced catalytically by NADH in the presence of the Beneckea harveyi NAD(P)H:(flavin) oxidoreductase, the reaction proceeding to an equilibrium with an equilibrium constant near unity. This implies an E0 of -0.310 V for the deazariboflavindihydrodeazariboflavin couple, much lower than that for isoalloxazines. With this enzyme, both riboflavin and deazariboflavin show the same stereospecificity with respect to the pyridine nucleotide, and despite a large difference in Vmax for the two, both have the same rate-determining step (hydrogen transfer). Direct transfer of the hydrogen is seen between the nicotinamide and deazariboflavin in both reaction directions. DeazaFMN reconstituted yeast NADPH: (acceptor) oxidoreductase (Old Yellow Enzyme), and deazaFAD reconstituted D-amino acid:O2 oxidoreductase and Aspergillus niger D-glucose O2 oxidoreductase are all reduced by substrate at approximately 10(-5) the rate of holoenzyme; none are reoxidized by oxygen or any of the tested artificial electron acceptors, though deazaFADH-bound to D-amino acid:O2 oxidoreductase is rapidly oxidized by the imino acid product. Direct hydrogen transfer from substrate to deazaflavin has been demonstrated for both deazaFAD-reconstituted oxidases. These data implicate deazaflavins as a unique probe of flavin catalysis, in that any mechanism for the flavin catalysis must account for the deazaflavin reactivity as well."}
{"id": "PMID:3208", "title": "Electrofocusing and kinetic studies of adult and embryonic chicken pyruvate kinases.", "content": "Chicken embryos less than 15 days old contain only the K isozyme of pyruvate kinase, which appears to exist in vivo as an R,T conformational set with pI values of 7.2 and 6.6, respectively. Sets of lower pI and higher pI K-isozyme variants also are obtained. Whole embryos of 15 days or more of development show progressively increasing amounts of higher pI, lower K0.5S enzymatic variants. Tissue distribution and kinetic properties suggest that the highest pI form (pH 8.8-9.0) is an M-isozyme analogue. The intermediate forms are postulated to be hybrids. Adult liver extracts contain only the embryonic K isozyme; no evidence for an L-isozyme analogue was obtained. All major forms of the enzymes are compared with respect to saturation by phosphoenolpyruvate in the absence of effector and in the presence of fructose 1,6-diphosphate, alanine, serine, phenylalanine, tryptophan, and/or Mg-ATP.", "contents": "Electrofocusing and kinetic studies of adult and embryonic chicken pyruvate kinases. Chicken embryos less than 15 days old contain only the K isozyme of pyruvate kinase, which appears to exist in vivo as an R,T conformational set with pI values of 7.2 and 6.6, respectively. Sets of lower pI and higher pI K-isozyme variants also are obtained. Whole embryos of 15 days or more of development show progressively increasing amounts of higher pI, lower K0.5S enzymatic variants. Tissue distribution and kinetic properties suggest that the highest pI form (pH 8.8-9.0) is an M-isozyme analogue. The intermediate forms are postulated to be hybrids. Adult liver extracts contain only the embryonic K isozyme; no evidence for an L-isozyme analogue was obtained. All major forms of the enzymes are compared with respect to saturation by phosphoenolpyruvate in the absence of effector and in the presence of fructose 1,6-diphosphate, alanine, serine, phenylalanine, tryptophan, and/or Mg-ATP."}
{"id": "PMID:3209", "title": "Characterization of a cytochrome P-450 dependent monoterpene hydroxylase from the higher plant Vinca rosea.", "content": "A monooxygenase isolated from 5-day old etiolated Vinca rosea seedlings was shown to catalyze the hydroxylation of the monoterpene alcohols, geraniol and nerol, to their corresponding 10-hydroxy derivatives. Hydroxylase activity was inpendent upon NADPH (neither NADH nor combination of NADH, NADP+ and ATP served as substitutes) and O2. Geraniol hydroxylation was enhanced by dithiothreitol (monothiols were less effective) and inhibited by phospholipases, thiol reagents, metyrapone, and cytochrome c, as well as other inhibitors of cytochrome P-450 systems. Geraniol was hydroxylated at a faster rate than nerol, but the alcohols possessed similar apparent Km values. The membrane-bound hydroxylase was solubilized by treatment with sodium cholate, Renex-30, or Lubrol-WX. Cholate-treated enzyme was resolved by DEAE-cellulose chromatography and reconstitution of the hydroxylase was effected utilizing different fractions containing cytochrome P-450, a NADPH-cytochrome c reductase, and lipid.", "contents": "Characterization of a cytochrome P-450 dependent monoterpene hydroxylase from the higher plant Vinca rosea. A monooxygenase isolated from 5-day old etiolated Vinca rosea seedlings was shown to catalyze the hydroxylation of the monoterpene alcohols, geraniol and nerol, to their corresponding 10-hydroxy derivatives. Hydroxylase activity was inpendent upon NADPH (neither NADH nor combination of NADH, NADP+ and ATP served as substitutes) and O2. Geraniol hydroxylation was enhanced by dithiothreitol (monothiols were less effective) and inhibited by phospholipases, thiol reagents, metyrapone, and cytochrome c, as well as other inhibitors of cytochrome P-450 systems. Geraniol was hydroxylated at a faster rate than nerol, but the alcohols possessed similar apparent Km values. The membrane-bound hydroxylase was solubilized by treatment with sodium cholate, Renex-30, or Lubrol-WX. Cholate-treated enzyme was resolved by DEAE-cellulose chromatography and reconstitution of the hydroxylase was effected utilizing different fractions containing cytochrome P-450, a NADPH-cytochrome c reductase, and lipid."}
{"id": "PMID:3210", "title": "Methionine sulfoxide cytochrome c.", "content": "Cytochrome c has been chemically modified by methylene blue mediated photooxidation. It is established that the methionine residues of the protein have been specifically converted to methionine sulfoxide residues. No oxidation of any other amino acid residues or the cysteine thioether bridges of the molecule occurs during the photooxidation reaction. The absorbance spectrum of methionine sulfoxide ferricytochrome c at neutrality is similar to that of the unmodified protein except for an increase in the extinction coefficient of the Soret absorbance band and for the complete loss of the ligand sensitive 695 nm absorbance band in the spectrum of the derivative. The protein remains in the low spin configuration which implies the retention of two strong field ligands. Spin state sensitive spectral titrations and model studies of heme peptides indicate that the sixth ligand is definitely not provided by a lysine residue but may be methionine-80 sulfoxide coordinated via its sulfur atom. Circular dichroism spectra indicate that the heme crevice of methionine sulfoxide ferri- and ferrocytochrome c is weakened relative to native cytochrome c. The redox potential of methionine sulfoxide cytochrome c is 184 mV which is markedly diminished from the 260 mV redox potential of native cytochrome c. The modified protein is equivalent to native cytochrome c as a substrate for cytochrome oxidase and is not autoxidizable at neutral pH but is virtually inactive with succinate-cytochrome c reductase. These results indicate that the major role of the methionine-80 in cytochrome c is to preserve a closed hydrophobic heme crevice which is essential for the maintainance of the necessary redox potential.", "contents": "Methionine sulfoxide cytochrome c. Cytochrome c has been chemically modified by methylene blue mediated photooxidation. It is established that the methionine residues of the protein have been specifically converted to methionine sulfoxide residues. No oxidation of any other amino acid residues or the cysteine thioether bridges of the molecule occurs during the photooxidation reaction. The absorbance spectrum of methionine sulfoxide ferricytochrome c at neutrality is similar to that of the unmodified protein except for an increase in the extinction coefficient of the Soret absorbance band and for the complete loss of the ligand sensitive 695 nm absorbance band in the spectrum of the derivative. The protein remains in the low spin configuration which implies the retention of two strong field ligands. Spin state sensitive spectral titrations and model studies of heme peptides indicate that the sixth ligand is definitely not provided by a lysine residue but may be methionine-80 sulfoxide coordinated via its sulfur atom. Circular dichroism spectra indicate that the heme crevice of methionine sulfoxide ferri- and ferrocytochrome c is weakened relative to native cytochrome c. The redox potential of methionine sulfoxide cytochrome c is 184 mV which is markedly diminished from the 260 mV redox potential of native cytochrome c. The modified protein is equivalent to native cytochrome c as a substrate for cytochrome oxidase and is not autoxidizable at neutral pH but is virtually inactive with succinate-cytochrome c reductase. These results indicate that the major role of the methionine-80 in cytochrome c is to preserve a closed hydrophobic heme crevice which is essential for the maintainance of the necessary redox potential."}
{"id": "PMID:3211", "title": "A kinetic study of protein-protein interactions.", "content": "Kinetic studies have been carried out of the monomer-dimer interaction of insulin, beta-lactoglobulin, and alpha-chymotrypsin using stopped-flow and temperature-jump techniques. The pH indicators bromothymol blue, bromophenol blue, and phenol red were used to monitor pH changes associated with the monomer-dimer interaction. In all three cases a kinetic process was observed which could be attributed to a simple monomer-dimer equilibrium, and association (k1) and dissociation (k-1) rate constants were determined. The results obtained are as follows: for insulin at 23 degrees C, pH 6.8, 0.125 M KNO3, k1 = 1.14 X 10(8) M-1 s-1, k-1 - 1.48 X 10(4)s(-1); for beta-lactoglobulin AB at 35 degrees C, pH 3.7, 0.025 M KNO3, d1 = 4.7 X 10(4) M-1 s-1, k-1 = 2.1 s-1; for alpha-chymotrypsin at 25 degreesC, pH 4.3, 0.05 M KNO3 k1 - 3.7 X 10(3) M-1 s-1, k-1 - 0.68 s-1. The kinetic behavior of the separated beta-lactoglobulin A and B was similar to that of the mixture. In the case of chymotrypsin, bromophenol blue was found to activate the enzyme catalyzed hydrolysis of p-nitrophenyl acetate, and a rate process was observed with the temperature jump which could be attributed to a conformational change of the indicator-protein complex. The association rate constant for dimer formation of insulin approaches the value expected for a diffusion-controlled process, while the values obtained for the other two proteins are below those expected for a diffusion-controlled reaction unless unusally large steric and electrostatic effects are present.", "contents": "A kinetic study of protein-protein interactions. Kinetic studies have been carried out of the monomer-dimer interaction of insulin, beta-lactoglobulin, and alpha-chymotrypsin using stopped-flow and temperature-jump techniques. The pH indicators bromothymol blue, bromophenol blue, and phenol red were used to monitor pH changes associated with the monomer-dimer interaction. In all three cases a kinetic process was observed which could be attributed to a simple monomer-dimer equilibrium, and association (k1) and dissociation (k-1) rate constants were determined. The results obtained are as follows: for insulin at 23 degrees C, pH 6.8, 0.125 M KNO3, k1 = 1.14 X 10(8) M-1 s-1, k-1 - 1.48 X 10(4)s(-1); for beta-lactoglobulin AB at 35 degrees C, pH 3.7, 0.025 M KNO3, d1 = 4.7 X 10(4) M-1 s-1, k-1 = 2.1 s-1; for alpha-chymotrypsin at 25 degreesC, pH 4.3, 0.05 M KNO3 k1 - 3.7 X 10(3) M-1 s-1, k-1 - 0.68 s-1. The kinetic behavior of the separated beta-lactoglobulin A and B was similar to that of the mixture. In the case of chymotrypsin, bromophenol blue was found to activate the enzyme catalyzed hydrolysis of p-nitrophenyl acetate, and a rate process was observed with the temperature jump which could be attributed to a conformational change of the indicator-protein complex. The association rate constant for dimer formation of insulin approaches the value expected for a diffusion-controlled process, while the values obtained for the other two proteins are below those expected for a diffusion-controlled reaction unless unusally large steric and electrostatic effects are present."}
{"id": "PMID:3212", "title": "Ionophore A23187: the effect of H+ concentration on complex formation with divalent and monovalent cations and the demonstration of K+ transport in mitochondria mediated by A23187.", "content": "The two-phase extraction technique has been used to study the equilibrium between A23187, metal cations, and H+. Under these conditions the ionophore forms charge neutral isostoichiometric complexes with divalent cations in which both carboxylate groups of the 2:1 A23187:M2+ complexes are deprotonated. In ethanol, however, the methyl ester of A23187 also binds divalent cations indicating that protonated complexes between A23187 and cations should also exist. With monovalent cations, A23187 forms two charge-neutral complexes of stoichiometries and relative stabilities: A2HM greater than AM. Examination of energy utilization K+ and H+ movements, and light scattering capacity of mitochondria in the presence of divalent cation chelators, A23187, and valinomycin demonstrates that A23187 can act as a nigericin type K+ ionophore under appropriate conditions. Formation constants for the A2HM complexes with monovalent cations indicate that with appropriate conditions transport of Li+ and Na+ mediated by A23187 would also be expected. The binding constant data and associated free energies of complex formation are compared as a function of ionic radius and of cation charge. The data indicate that lack of conformational mobility in A23187 is responsible for the high cation size selectivity of this compound. To explain the transport selectivity of A23187 for divalent cations, it is proposed that this ionophore forms a family of five complexes, isostoichiometric between cations of different valence but of which only charge-neutral species are permeant to membranes. The charge of a given complex is in turn determined by that of the cation. The concept is consistent with the divalent cation transport specificity of A23187, explains the observed monovalent cation transport, and is useful in rationalizing the differences in charge selectivity between A23187 and X-537A.", "contents": "Ionophore A23187: the effect of H+ concentration on complex formation with divalent and monovalent cations and the demonstration of K+ transport in mitochondria mediated by A23187. The two-phase extraction technique has been used to study the equilibrium between A23187, metal cations, and H+. Under these conditions the ionophore forms charge neutral isostoichiometric complexes with divalent cations in which both carboxylate groups of the 2:1 A23187:M2+ complexes are deprotonated. In ethanol, however, the methyl ester of A23187 also binds divalent cations indicating that protonated complexes between A23187 and cations should also exist. With monovalent cations, A23187 forms two charge-neutral complexes of stoichiometries and relative stabilities: A2HM greater than AM. Examination of energy utilization K+ and H+ movements, and light scattering capacity of mitochondria in the presence of divalent cation chelators, A23187, and valinomycin demonstrates that A23187 can act as a nigericin type K+ ionophore under appropriate conditions. Formation constants for the A2HM complexes with monovalent cations indicate that with appropriate conditions transport of Li+ and Na+ mediated by A23187 would also be expected. The binding constant data and associated free energies of complex formation are compared as a function of ionic radius and of cation charge. The data indicate that lack of conformational mobility in A23187 is responsible for the high cation size selectivity of this compound. To explain the transport selectivity of A23187 for divalent cations, it is proposed that this ionophore forms a family of five complexes, isostoichiometric between cations of different valence but of which only charge-neutral species are permeant to membranes. The charge of a given complex is in turn determined by that of the cation. The concept is consistent with the divalent cation transport specificity of A23187, explains the observed monovalent cation transport, and is useful in rationalizing the differences in charge selectivity between A23187 and X-537A."}
{"id": "PMID:3213", "title": "Properties of the tetrodotoxin binding component in plasma membranes isolated from Electrophorus electricus.", "content": "The biochemical properties of the electrically excitable sodium channels in the electroplaque of Electrophorus electricus were investigated using tritiated tetrodotoxin (TTX) as a specific membrane probe. Membrane fragments from the electroplaque were isolated essentially by differential centrifugation and characterized with respect to the plasma membrane markers acetylcholine receptors, acetylcholinesterase, (Na+ + K+)ATPase, and [3H]TTX binding. Equilibrium binding studies showed that [3H]TTX bound to a single population of noninteracting receptor sites with an apparent dissociation constant of 6 +/- 1 X 10(-9) M. The toxin-membrane complex dissociated with a first-order rate constant of 0.012 sec-1. Studies on the pH dependence of complex formation demonstrated the requirement for an ionizable, functional group with a pK of 5.3 and this group has been shown to be a carboxyl. Treatment of the membranes with trimethyloxonium tetrafluoroborate, a carboxyl group modifying reagent, resulted in an irreversible loss in the binding of [3H]TTX, which could be prevented by low concentrations of TTX or saxitoxin. This decrease was due to a reduction in the total number of binding sites and not to a decrease in toxin binding affinities. The relative binding affinities of various monovalent alkali metal and polyatomic cations for the TTX-receptor site showed that this site displayed cation discrimination properties which were similar to those reported previously for the electrically excitable sodium channel in intact nerve fibers. A possible role for this site in the ion selectivity of the sodium channel is proposed.", "contents": "Properties of the tetrodotoxin binding component in plasma membranes isolated from Electrophorus electricus. The biochemical properties of the electrically excitable sodium channels in the electroplaque of Electrophorus electricus were investigated using tritiated tetrodotoxin (TTX) as a specific membrane probe. Membrane fragments from the electroplaque were isolated essentially by differential centrifugation and characterized with respect to the plasma membrane markers acetylcholine receptors, acetylcholinesterase, (Na+ + K+)ATPase, and [3H]TTX binding. Equilibrium binding studies showed that [3H]TTX bound to a single population of noninteracting receptor sites with an apparent dissociation constant of 6 +/- 1 X 10(-9) M. The toxin-membrane complex dissociated with a first-order rate constant of 0.012 sec-1. Studies on the pH dependence of complex formation demonstrated the requirement for an ionizable, functional group with a pK of 5.3 and this group has been shown to be a carboxyl. Treatment of the membranes with trimethyloxonium tetrafluoroborate, a carboxyl group modifying reagent, resulted in an irreversible loss in the binding of [3H]TTX, which could be prevented by low concentrations of TTX or saxitoxin. This decrease was due to a reduction in the total number of binding sites and not to a decrease in toxin binding affinities. The relative binding affinities of various monovalent alkali metal and polyatomic cations for the TTX-receptor site showed that this site displayed cation discrimination properties which were similar to those reported previously for the electrically excitable sodium channel in intact nerve fibers. A possible role for this site in the ion selectivity of the sodium channel is proposed."}
{"id": "PMID:3214", "title": "The arrangement of subunits in cholera toxin.", "content": "Cholera toxin consists of five similar B subunits of apparent molecular weight about 10 600 and one A subunit (29 000) consisting of two peptides (A1 23 000-24 000 and A2 about 5500) linked by a single disulfide bond. Each B subunit also contains one internal disulfide bond which is readily reduced but is protected from carboxymethylation unless the reduced subunits are heated in urea. Tyrosine residues in A1 and in B subunits are readily iodinated, but the intact B assembly does not react with iodine. Upon reaction with the cross-linking reagent dimethyl suberimidate, B subunits may be covalently connected to each other, to A1 and to A2. A1 and A2 may also be cross-linked. The B subunits are probably arranged in a ring with A on the axis. A2 is required for the re-assembly of toxin from its subunits and may serve to hold A1 on the B ring. The maximum activity of cholera toxin in vitro is obtained only when the active peptide, A1, is separated from the rest of the molecule. Such separation, and the insertion of A1 into the cytosol, must follow the binding of the complete toxin, through component B, to the exterior of intact cells. This binding increases the effective concentration of the toxin in the vicinity of the plasma membrane. Possible ways in which A1 then crosses the membrane are considered in the Discussion.", "contents": "The arrangement of subunits in cholera toxin. Cholera toxin consists of five similar B subunits of apparent molecular weight about 10 600 and one A subunit (29 000) consisting of two peptides (A1 23 000-24 000 and A2 about 5500) linked by a single disulfide bond. Each B subunit also contains one internal disulfide bond which is readily reduced but is protected from carboxymethylation unless the reduced subunits are heated in urea. Tyrosine residues in A1 and in B subunits are readily iodinated, but the intact B assembly does not react with iodine. Upon reaction with the cross-linking reagent dimethyl suberimidate, B subunits may be covalently connected to each other, to A1 and to A2. A1 and A2 may also be cross-linked. The B subunits are probably arranged in a ring with A on the axis. A2 is required for the re-assembly of toxin from its subunits and may serve to hold A1 on the B ring. The maximum activity of cholera toxin in vitro is obtained only when the active peptide, A1, is separated from the rest of the molecule. Such separation, and the insertion of A1 into the cytosol, must follow the binding of the complete toxin, through component B, to the exterior of intact cells. This binding increases the effective concentration of the toxin in the vicinity of the plasma membrane. Possible ways in which A1 then crosses the membrane are considered in the Discussion."}
{"id": "PMID:3215", "title": "Kinetics of reaction of anions with methemerythrin derivatives.", "content": "The kinetics of anation of methemerythrin over a wide range of pH and concentration of anions have been studied at 25 degrees C. The azide and thiocyanate ions have been most intensively investigated but experiments with fluoride and chloride are also reported. The replacement of anion in methemerythrin-anionic adducts by other anions has also been studied. Except for replacement of met-fluoride by azide, all replacements can be explained by a dissociative mechanism via the aquated species. Anations are second-order and an associative mechanism is preferred. The second-order rate constant decreases with increasing anion concentrations (from 20 muM to 20 mM). This is attributed to the effect of a secondary anion binding site. The behavior of octameric and monomeric forms of the protein toward thiocyanate is identical. A comparison of results with simple Fe(III) complexes and certain metalloproteins is made.", "contents": "Kinetics of reaction of anions with methemerythrin derivatives. The kinetics of anation of methemerythrin over a wide range of pH and concentration of anions have been studied at 25 degrees C. The azide and thiocyanate ions have been most intensively investigated but experiments with fluoride and chloride are also reported. The replacement of anion in methemerythrin-anionic adducts by other anions has also been studied. Except for replacement of met-fluoride by azide, all replacements can be explained by a dissociative mechanism via the aquated species. Anations are second-order and an associative mechanism is preferred. The second-order rate constant decreases with increasing anion concentrations (from 20 muM to 20 mM). This is attributed to the effect of a secondary anion binding site. The behavior of octameric and monomeric forms of the protein toward thiocyanate is identical. A comparison of results with simple Fe(III) complexes and certain metalloproteins is made."}
{"id": "PMID:3216", "title": "Comparative studies on the structure and aggregative properties of the myosin molecule. III. The in vitro aggregative properties of the lobster myosin molecule.", "content": "The solubility of rabbit skeletal and lobster abdominal muscle myosin has been studied in monovalent salt solutions as a function of pH (over the range 4.75 to 8.5) and ionic strength (50-500 mM). Rabbit skeletal muscle myosin was found to precipitate over a narrower pH range than the lobster abdominal muscle myosin but at equivalent pH values and ionic strengths the former exhibited greater solubility. Comparison of the solubility of rabbit myosin, per se with that of light meromyosin and lobster myosin with its equivalent proteolytically produced fragment (fraction B1) showed that both rod fragments were more soluble than their parent molecules. Under conditions of low solubility (low ionic strength and pH) the quantitiy of protein in solution remained essentially constant with increasing total protein, thus suggesting that the aggregation phenomenon is of a phase transition type. Examination of the aggregates by electron microscopy revealed that rabbit myosin formed classical, elongate, spindle-shaped filaments similar to those previously observed by others. In contrast lobster myosin only formed short, dumbbell-shaped filaments 0.2-0.3 mum long. Consideration of the pH ranges over which aggregation occurred suggests that protonation of histidine residues may be involved in rabbit myosin filament formation while for lobster myosin, aggregation may involve protonation of epsilon-amino or guanidino groups. The possible relationship between the distribution of these groups along the rod portion of the myosin molecule and the formation of elongate filaments has been explored.", "contents": "Comparative studies on the structure and aggregative properties of the myosin molecule. III. The in vitro aggregative properties of the lobster myosin molecule. The solubility of rabbit skeletal and lobster abdominal muscle myosin has been studied in monovalent salt solutions as a function of pH (over the range 4.75 to 8.5) and ionic strength (50-500 mM). Rabbit skeletal muscle myosin was found to precipitate over a narrower pH range than the lobster abdominal muscle myosin but at equivalent pH values and ionic strengths the former exhibited greater solubility. Comparison of the solubility of rabbit myosin, per se with that of light meromyosin and lobster myosin with its equivalent proteolytically produced fragment (fraction B1) showed that both rod fragments were more soluble than their parent molecules. Under conditions of low solubility (low ionic strength and pH) the quantitiy of protein in solution remained essentially constant with increasing total protein, thus suggesting that the aggregation phenomenon is of a phase transition type. Examination of the aggregates by electron microscopy revealed that rabbit myosin formed classical, elongate, spindle-shaped filaments similar to those previously observed by others. In contrast lobster myosin only formed short, dumbbell-shaped filaments 0.2-0.3 mum long. Consideration of the pH ranges over which aggregation occurred suggests that protonation of histidine residues may be involved in rabbit myosin filament formation while for lobster myosin, aggregation may involve protonation of epsilon-amino or guanidino groups. The possible relationship between the distribution of these groups along the rod portion of the myosin molecule and the formation of elongate filaments has been explored."}
{"id": "PMID:3217", "title": "Properties of cholera toxin- and NaF-stimulated adenylate cyclase from mouse thymocytes.", "content": "Kinetic parameters of mouse thymocyte adenylate cyclase activity were determined. NaF and cholera toxin stimulated adenylate cyclase. Stimulation by either agent did not change the pH or Mg2+ optima relative to control (unstimulated cyclase). The Km value for ATP of adenylate cyclase stimulated by NaF was significantly reduced from control. By contrast, cholera toxin treatment did not change the Km relative to control. Adenylate cyclase, when stimulated by NaF, had an optimum for Mn2+ alone, or Mn2+ in combination with Mg2+, at least twice that of control. In contrast, cyclase activity prepared from cells treated with cholera toxin remained unchanged with regard to these divalent cations when compared to control. Addition of NaF to adenylate cyclase prepared from cells treated with cholera toxin resulted in a significant reduction (30%) in activity suggesting that both NaF and cholera toxin were acting on the same cyclase. NaF inhibition of cholera toxin-stimulated activity was shown to be a direct interaction of fluoride on the stimulated cyclase enzyme. This inhibition appeared to be immediate and independent on pH, Mg2+ or ATP concentrations. Although NaF inhibition was lost when Mn2+ was present in the reaction mixture, the activity expressed by addition of NaF to cyclase prepared from cholera toxin-treated cells was much less than by addition of NaF to control. As observed with cholera toxin stimulation alone, activity expressed by the inhibited enzyme (cholera toxin treated + NaF) exhibited a Km for ATP and an optimum for Mn2+ alone or in combination with Mg2+ similar to control.", "contents": "Properties of cholera toxin- and NaF-stimulated adenylate cyclase from mouse thymocytes. Kinetic parameters of mouse thymocyte adenylate cyclase activity were determined. NaF and cholera toxin stimulated adenylate cyclase. Stimulation by either agent did not change the pH or Mg2+ optima relative to control (unstimulated cyclase). The Km value for ATP of adenylate cyclase stimulated by NaF was significantly reduced from control. By contrast, cholera toxin treatment did not change the Km relative to control. Adenylate cyclase, when stimulated by NaF, had an optimum for Mn2+ alone, or Mn2+ in combination with Mg2+, at least twice that of control. In contrast, cyclase activity prepared from cells treated with cholera toxin remained unchanged with regard to these divalent cations when compared to control. Addition of NaF to adenylate cyclase prepared from cells treated with cholera toxin resulted in a significant reduction (30%) in activity suggesting that both NaF and cholera toxin were acting on the same cyclase. NaF inhibition of cholera toxin-stimulated activity was shown to be a direct interaction of fluoride on the stimulated cyclase enzyme. This inhibition appeared to be immediate and independent on pH, Mg2+ or ATP concentrations. Although NaF inhibition was lost when Mn2+ was present in the reaction mixture, the activity expressed by addition of NaF to cyclase prepared from cholera toxin-treated cells was much less than by addition of NaF to control. As observed with cholera toxin stimulation alone, activity expressed by the inhibited enzyme (cholera toxin treated + NaF) exhibited a Km for ATP and an optimum for Mn2+ alone or in combination with Mg2+ similar to control."}
{"id": "PMID:3218", "title": "Regulation of the NADH and NADPH-ferredoxin oxidoreductases in clostridia of the butyric group.", "content": "NADH and NADPH-ferredoxin oxidoreductases have been studied in Clostridium acetobutylicum, Cl. tyrobutyricum and Cl. pasteurianum. The study of the distribution and regulation of these enzymatic activities in well-defined culture conditions, reveals that the essential function of NADPH-ferredoxin oxidoreductase is to produce NADPH, while NADH-ferredoxin oxidoreductase can, depending on cellular conditions, produce or oxidize NADH. When these Clostridia use glycolysis, regulation of the NADH-ferredoxin oxidoreductase by acetyl-CoA (obligatory activator of NADH-ferroxin reductase activity) and by NADH (competitive inhibitor of ferredoxin-NAD+ reductase activity) allow the enzymes to function correlatively with glyceraldehyde-3-phosphate dehydrogenase and thus control the levels of NAD+ and NADH in the cell. In Cl. tyrobutyricum and Cl. pasteurianum, the ferredoxin-NADP+ reductase  activities are regulated by NAD+ and NADH in accordance with the intracellular concentrations of these coenzymes. In Cl. tyrobutyricum growing on pyruvate/acetate, NADH and NADPH-ferredoxin reductase activities cannot be detected; only the ferredoxin-NAD+ and ferredoxin-NADP+ reductase activities are found. In this Clostridium, regulation of the ferredoxin-NADP+ reductase activity is the same whether it is grown on glucose or pyruvate. Contrary to this, the ferredoxin-NAD+ reductase activity undergoes a drastic change, since NADH no longer controls the enzymatic activity. In this case regulation is no longer necessary, since glyceraldehyde-3-phosphate dehydrogenase does not function.", "contents": "Regulation of the NADH and NADPH-ferredoxin oxidoreductases in clostridia of the butyric group. NADH and NADPH-ferredoxin oxidoreductases have been studied in Clostridium acetobutylicum, Cl. tyrobutyricum and Cl. pasteurianum. The study of the distribution and regulation of these enzymatic activities in well-defined culture conditions, reveals that the essential function of NADPH-ferredoxin oxidoreductase is to produce NADPH, while NADH-ferredoxin oxidoreductase can, depending on cellular conditions, produce or oxidize NADH. When these Clostridia use glycolysis, regulation of the NADH-ferredoxin oxidoreductase by acetyl-CoA (obligatory activator of NADH-ferroxin reductase activity) and by NADH (competitive inhibitor of ferredoxin-NAD+ reductase activity) allow the enzymes to function correlatively with glyceraldehyde-3-phosphate dehydrogenase and thus control the levels of NAD+ and NADH in the cell. In Cl. tyrobutyricum and Cl. pasteurianum, the ferredoxin-NADP+ reductase  activities are regulated by NAD+ and NADH in accordance with the intracellular concentrations of these coenzymes. In Cl. tyrobutyricum growing on pyruvate/acetate, NADH and NADPH-ferredoxin reductase activities cannot be detected; only the ferredoxin-NAD+ and ferredoxin-NADP+ reductase activities are found. In this Clostridium, regulation of the ferredoxin-NADP+ reductase activity is the same whether it is grown on glucose or pyruvate. Contrary to this, the ferredoxin-NAD+ reductase activity undergoes a drastic change, since NADH no longer controls the enzymatic activity. In this case regulation is no longer necessary, since glyceraldehyde-3-phosphate dehydrogenase does not function."}
{"id": "PMID:3219", "title": "Lysophospholipase activity in cell-wall fragments contaminating mitochondrial fractions of Neurospora crassa.", "content": "Crude mitochondrial preparations from Neurospora crassa contain high levels of lysophospholipase (EC 3.1.1.5) activity when assayed with lysophosphatidylcholine as a substrate. In mitochondria purified by centrifugation on a sucrose-density gradient this activity is virtually absent. The enzyme was shown to be linked to a contaminating cell fraction which mainly consists of cell-wall material as was demonstrated by electron microscopy and chemical analysis. The enzyme has no absolute Ca2+ requirement but it is slightly stimulated by 10 mM CaCl2. The pH optimum is 5.8 in presence of CaCl2 and is shifted to 4.2 when EDTA is present. In contrast to other lysophospholipases this enzyme is only slightly inhibited by deoxycholate. This detergent is able to release part of the lysophospholipase activity from the wall fragments without producing an increase in specific activity. The enzyme is possibly secreted by the cells as high lysophospholipase activities were also found in the culture medium.", "contents": "Lysophospholipase activity in cell-wall fragments contaminating mitochondrial fractions of Neurospora crassa. Crude mitochondrial preparations from Neurospora crassa contain high levels of lysophospholipase (EC 3.1.1.5) activity when assayed with lysophosphatidylcholine as a substrate. In mitochondria purified by centrifugation on a sucrose-density gradient this activity is virtually absent. The enzyme was shown to be linked to a contaminating cell fraction which mainly consists of cell-wall material as was demonstrated by electron microscopy and chemical analysis. The enzyme has no absolute Ca2+ requirement but it is slightly stimulated by 10 mM CaCl2. The pH optimum is 5.8 in presence of CaCl2 and is shifted to 4.2 when EDTA is present. In contrast to other lysophospholipases this enzyme is only slightly inhibited by deoxycholate. This detergent is able to release part of the lysophospholipase activity from the wall fragments without producing an increase in specific activity. The enzyme is possibly secreted by the cells as high lysophospholipase activities were also found in the culture medium."}
{"id": "PMID:3220", "title": "Purification and properties of cholesterol ester hydrolase from human aortic intima and media.", "content": "1. Cholesterol ester hydrolase of human aortic intima and media was isolated and purified about 650-fold with 10-15% recovery of the original activity by sequential precipitation with 35% acetone, gel filtration on Sephadex G-75 and DEAE-cellulose column chromatography. 2. Two pH optima of 4.5-5.0 and 7.0-7.5 were consistently observed for the partially purified cholesterol ester hydrolase of human aortic intima and media. 3. In the system used in the present study, the increasing concentration of emulsifiers, sodium taurocholate and phosphatidylcholine, inhibited the activity of the neutral enzymes but not on the acid enzymes. On the contrary, reaction products, cholesterol and oleic acid, were much more inhibitory on the acid enzymes than on the neutral ones. 4. Results of studies on the effect of presentation of substrate on the enzyme activity and on the difference between acid and neutral enzymes are also discussed.", "contents": "Purification and properties of cholesterol ester hydrolase from human aortic intima and media. 1. Cholesterol ester hydrolase of human aortic intima and media was isolated and purified about 650-fold with 10-15% recovery of the original activity by sequential precipitation with 35% acetone, gel filtration on Sephadex G-75 and DEAE-cellulose column chromatography. 2. Two pH optima of 4.5-5.0 and 7.0-7.5 were consistently observed for the partially purified cholesterol ester hydrolase of human aortic intima and media. 3. In the system used in the present study, the increasing concentration of emulsifiers, sodium taurocholate and phosphatidylcholine, inhibited the activity of the neutral enzymes but not on the acid enzymes. On the contrary, reaction products, cholesterol and oleic acid, were much more inhibitory on the acid enzymes than on the neutral ones. 4. Results of studies on the effect of presentation of substrate on the enzyme activity and on the difference between acid and neutral enzymes are also discussed."}
{"id": "PMID:3221", "title": "Effect of maternal diet on fetal hepatic lipogenesis.", "content": "The effects of: a, maternal diet; b, cyclic-3',5'-adenosinemonophosphate (cyclic AMP) and c, clofibrate on hepatic lipogenesis in fetal rats were studied. The experimental diets contained 22% protein, 40--50% carbohydrate, adequate vitamins, and minerals. In addition, the fat-containing diets were supplemented with either 15% corn oil, 25% corn oil, or 5% cholesterol + 10% oleic acid. In the clofibrate feeding studies, 0.3% (w/v) of the ethyl ester was added to a stock ration or to fat-free diet. Lipogenesis was measured in liver slices incubated with [2-14C]pyruvate, [1-14C]acetate, or 3H2O. In addition, activities of lipogenic enzymes were measured in cytosol fractions from liver homogenates. The effec-s of the experimental diets on liver composition were also examined. Lipogenic activity was higher in fetal than in maternal liver. When 15% corn oil was added to the maternal diet, fatty acid synthesis in fetal liver did not decrease as it did in maternal liver. Maternal fasting decreased fetal fatty acid synthesys by 50% when measured with 14C and less than 10% when measured with 3H2O. Although the addition of cholesterol to the maternal diet decreased cholesterol synthesis in maternal liver, no such decrease was observed in fetal liver. Changes in enzyme activities paralleled alterations in lipogenesis in maternal but not in fetal liver. Corn oil feeding or fasting increased the rate of transfer of linoleate from the dam to the fetus. However, accumulation of linoleate in fetal liver did not correlate with a decreased rate of fatty acid synthesis as it did in maternal liver. Maternal hepatic glycogen stores were depleted by fasting, but glycogen levels in fetal liver remained high under these conditions.", "contents": "Effect of maternal diet on fetal hepatic lipogenesis. The effects of: a, maternal diet; b, cyclic-3',5'-adenosinemonophosphate (cyclic AMP) and c, clofibrate on hepatic lipogenesis in fetal rats were studied. The experimental diets contained 22% protein, 40--50% carbohydrate, adequate vitamins, and minerals. In addition, the fat-containing diets were supplemented with either 15% corn oil, 25% corn oil, or 5% cholesterol + 10% oleic acid. In the clofibrate feeding studies, 0.3% (w/v) of the ethyl ester was added to a stock ration or to fat-free diet. Lipogenesis was measured in liver slices incubated with [2-14C]pyruvate, [1-14C]acetate, or 3H2O. In addition, activities of lipogenic enzymes were measured in cytosol fractions from liver homogenates. The effec-s of the experimental diets on liver composition were also examined. Lipogenic activity was higher in fetal than in maternal liver. When 15% corn oil was added to the maternal diet, fatty acid synthesis in fetal liver did not decrease as it did in maternal liver. Maternal fasting decreased fetal fatty acid synthesys by 50% when measured with 14C and less than 10% when measured with 3H2O. Although the addition of cholesterol to the maternal diet decreased cholesterol synthesis in maternal liver, no such decrease was observed in fetal liver. Changes in enzyme activities paralleled alterations in lipogenesis in maternal but not in fetal liver. Corn oil feeding or fasting increased the rate of transfer of linoleate from the dam to the fetus. However, accumulation of linoleate in fetal liver did not correlate with a decreased rate of fatty acid synthesis as it did in maternal liver. Maternal hepatic glycogen stores were depleted by fasting, but glycogen levels in fetal liver remained high under these conditions."}
{"id": "PMID:3222", "title": "Translational control of protein synthesis in stimulated WI-38 fibroblasts.", "content": "A cell-free protein synthesis system employing ribosomes from WI-38 human diploid fibroblasts was developed and its optimum MgC12 and KC1 levels and pH value found. The rate at which ribosomes are able to incorporate radioactive leucine into proteins ([14C]leucine incorporation/10 min/100 mug rRNA) and the number of growing peptide chains [3H]puromycinpeptides formed/100 mug rRNA) was determined. When confluent monolayers of WI-38 cells were stimulated to proliferate by serum, a transient increase in the rate of peptide elongation by ribosomes was observed at 60 min after stimulation. This increase was not affected by the presence of actinomycin D (10 mug/ml) in the stimulating medium. A change in the relative amount of certain ribosome-associated proteins accompanied the increased elongation rate of peptide growth. The alteration in associated proteins could not be accounted for by an increased synthesis of protein. Finally, the early activation of ribosomes in stimulated WI-38 cells appears to result from the removal of an inhibitor(s) of ribosome function.", "contents": "Translational control of protein synthesis in stimulated WI-38 fibroblasts. A cell-free protein synthesis system employing ribosomes from WI-38 human diploid fibroblasts was developed and its optimum MgC12 and KC1 levels and pH value found. The rate at which ribosomes are able to incorporate radioactive leucine into proteins ([14C]leucine incorporation/10 min/100 mug rRNA) and the number of growing peptide chains [3H]puromycinpeptides formed/100 mug rRNA) was determined. When confluent monolayers of WI-38 cells were stimulated to proliferate by serum, a transient increase in the rate of peptide elongation by ribosomes was observed at 60 min after stimulation. This increase was not affected by the presence of actinomycin D (10 mug/ml) in the stimulating medium. A change in the relative amount of certain ribosome-associated proteins accompanied the increased elongation rate of peptide growth. The alteration in associated proteins could not be accounted for by an increased synthesis of protein. Finally, the early activation of ribosomes in stimulated WI-38 cells appears to result from the removal of an inhibitor(s) of ribosome function."}
{"id": "PMID:3223", "title": "A non-equilibrium thermodynamics analysis of active transport within the framework of the chemiosotic theory.", "content": "The proton circuit devised by Mitchell in the chemiosmotic theory was subjected to analysis using the formalism of irreversible thermodynamics. The phenomenological coefficients and the degree of coupling relating co-permeant flows were derived from anion/H+, substrate/H+, cation/H+ and anion/anion biporter models. Linearity and equality of the cross-coefficients in Onsager relations were always satisfied. Macroscopic flows leading to charges splitting, such as oxido-reduction, hydro-dehydratation and transhydrogenase, are driven by a composite thermodynamic force which includes the proton-motive component. Multiple coupling occurs in the circuit when it is assumed that the net inward flux of protons becomes zero, i.e. when the circulation of protons reaches a stationary state. Under these conditions, oxidative phosphorylation, ATPase- or respiration-linked transhydrogenase and uptake of anion or cation against their electrochemical gradient may be predicted, in agreement with known experimental evidence.", "contents": "A non-equilibrium thermodynamics analysis of active transport within the framework of the chemiosotic theory. The proton circuit devised by Mitchell in the chemiosmotic theory was subjected to analysis using the formalism of irreversible thermodynamics. The phenomenological coefficients and the degree of coupling relating co-permeant flows were derived from anion/H+, substrate/H+, cation/H+ and anion/anion biporter models. Linearity and equality of the cross-coefficients in Onsager relations were always satisfied. Macroscopic flows leading to charges splitting, such as oxido-reduction, hydro-dehydratation and transhydrogenase, are driven by a composite thermodynamic force which includes the proton-motive component. Multiple coupling occurs in the circuit when it is assumed that the net inward flux of protons becomes zero, i.e. when the circulation of protons reaches a stationary state. Under these conditions, oxidative phosphorylation, ATPase- or respiration-linked transhydrogenase and uptake of anion or cation against their electrochemical gradient may be predicted, in agreement with known experimental evidence."}
{"id": "PMID:3224", "title": "Kinetics of the slow variation of peak sodium current in the membrane of myelinated nerve following changes of holding potential or extracellular pH.", "content": "(1) Changes of the holding potential applied to the membrane of myelinated nerve fibres induced slow variations of the peak sodium current, which are super-imposed on the effect of sodium inactivation. (2) These slow variations are transitions between various steady levels of available sodium conductance. Their time course can be described by the function erfc (square root t/tau) where tau is the time and erfc the error function complement. The characteristic time tau lies in the range 2-4 min and depends on the membrane potential. (3) Changes of extracellular pH cause a rapid change of the peak sodium current followed by a slow variation as observed after changes of the holding potential. This slow variation can be prevented by applying simultaneously an appropriate change of the holding potential, e.g. the effect of changing pH from 7.3 to 5.3 is balanced by changing the potential from --70 to --55 mV. (4) The results are interpreted by postulating charged components diffusion slowly within the nodal membrane. Their transverse distribution controls the number of sodium channels available at a given membrane potential. The equivalence between change of pH and voltage is explained by assuming negative fixed charges at the outer surface of the membrane, which are protonated at low pH and thus affect the intrinsic membrane potential. (5) It is concluded that effects which are ascribed to the action of agents on individual sodium channels have to be corrected for variations in the number of available channels if these agents influence the intrinsic membrane potential, e.g. changes of extracellular pH.", "contents": "Kinetics of the slow variation of peak sodium current in the membrane of myelinated nerve following changes of holding potential or extracellular pH. (1) Changes of the holding potential applied to the membrane of myelinated nerve fibres induced slow variations of the peak sodium current, which are super-imposed on the effect of sodium inactivation. (2) These slow variations are transitions between various steady levels of available sodium conductance. Their time course can be described by the function erfc (square root t/tau) where tau is the time and erfc the error function complement. The characteristic time tau lies in the range 2-4 min and depends on the membrane potential. (3) Changes of extracellular pH cause a rapid change of the peak sodium current followed by a slow variation as observed after changes of the holding potential. This slow variation can be prevented by applying simultaneously an appropriate change of the holding potential, e.g. the effect of changing pH from 7.3 to 5.3 is balanced by changing the potential from --70 to --55 mV. (4) The results are interpreted by postulating charged components diffusion slowly within the nodal membrane. Their transverse distribution controls the number of sodium channels available at a given membrane potential. The equivalence between change of pH and voltage is explained by assuming negative fixed charges at the outer surface of the membrane, which are protonated at low pH and thus affect the intrinsic membrane potential. (5) It is concluded that effects which are ascribed to the action of agents on individual sodium channels have to be corrected for variations in the number of available channels if these agents influence the intrinsic membrane potential, e.g. changes of extracellular pH."}
{"id": "PMID:3225", "title": "Effects of pH during recombination of human erythrocyte membrane apoprotein and lipid.", "content": "The recombinates from human red cell membrane proteins and lipids resulting from dialysis of the components in 2-chloroethanol against aqueous buffers from pH2-12 have been studied by density gradient centrifugation, polyacrylamide gel electrophoresis and freeze-fracture electron microscopy. Between pH 4 and 10 most of the proteins were found in the recombinates whereas below pH 4 and above pH 10 only part of them were recovered in the lipoprotein band after density gradient centrifugation. At low pH, increasing incorporation of the \"major glycoprotein\" into the recombinates was detected by gel electrophoresis and in parallel increasing amounts of particles were found in the freeze-fracture membrane faces. The necessity of working at low pH values from pH 2-4, however, and a critical evaluation of all the data presently available leads to the conclusion that the 2-choloroethanol technique is not adequate for recombination studies tending to membrane reconsitution.", "contents": "Effects of pH during recombination of human erythrocyte membrane apoprotein and lipid. The recombinates from human red cell membrane proteins and lipids resulting from dialysis of the components in 2-chloroethanol against aqueous buffers from pH2-12 have been studied by density gradient centrifugation, polyacrylamide gel electrophoresis and freeze-fracture electron microscopy. Between pH 4 and 10 most of the proteins were found in the recombinates whereas below pH 4 and above pH 10 only part of them were recovered in the lipoprotein band after density gradient centrifugation. At low pH, increasing incorporation of the \"major glycoprotein\" into the recombinates was detected by gel electrophoresis and in parallel increasing amounts of particles were found in the freeze-fracture membrane faces. The necessity of working at low pH values from pH 2-4, however, and a critical evaluation of all the data presently available leads to the conclusion that the 2-choloroethanol technique is not adequate for recombination studies tending to membrane reconsitution."}
{"id": "PMID:3226", "title": "[pH dependence and EPR spectra of Fe-NO complexes with purines and pyrimidines].", "content": "Equilibria between different types of Fe(I)-dinitrosyl complexes with nucleobases in solution were studied by means of EPR spectroscopy. Computer simulation and 15NO isotopic substitution were used in order to make easier the interpretation of complicated EPR patterns. The pH dependence of the purine and pyrimidine complexes was investigated. Several EPR signals, under slow exchange conditions, were present in the range of pH values of biological significance. Four types of complexes were identified on the basis of the nuclear hyperfine structure: B' = where two purine molecules were bound to iron via N-7 in the imidazole ring; B'' = where two mercapto-base molecules were bound to iron via S-; B''' = where one mercapto-base molecule was bound to iron via S- and another via pyrimidine-nitrogen; B* = where two pyrimidine molecules were bound to iron via pyrimidine-nitrogen.", "contents": "[pH dependence and EPR spectra of Fe-NO complexes with purines and pyrimidines]. Equilibria between different types of Fe(I)-dinitrosyl complexes with nucleobases in solution were studied by means of EPR spectroscopy. Computer simulation and 15NO isotopic substitution were used in order to make easier the interpretation of complicated EPR patterns. The pH dependence of the purine and pyrimidine complexes was investigated. Several EPR signals, under slow exchange conditions, were present in the range of pH values of biological significance. Four types of complexes were identified on the basis of the nuclear hyperfine structure: B' = where two purine molecules were bound to iron via N-7 in the imidazole ring; B'' = where two mercapto-base molecules were bound to iron via S-; B''' = where one mercapto-base molecule was bound to iron via S- and another via pyrimidine-nitrogen; B* = where two pyrimidine molecules were bound to iron via pyrimidine-nitrogen."}
{"id": "PMID:3237", "title": "Maximization of steady-state bacterial production in a chemostat with pH and substrate control.", "content": "This analytical study deals with the steady-state behavior and control of microbial growth in continuous cultures. A second order Haldane-Monod model of continuous cultures is used as a basis for study of the effects of the adjustment of pH by the addition of acidic (or basic) materials. The treatment of a hydrogen ion concentration, in addition to substrate and microbial concentrations as state variables, results in a third order system of equations describing the process. The analysis of the system in equilibrium yields several admissible steady states, that is, steady states which satisfy all constraints. An optimal control problem is formulated and subsequently solved to maximize steady-state microbial production.", "contents": "Maximization of steady-state bacterial production in a chemostat with pH and substrate control. This analytical study deals with the steady-state behavior and control of microbial growth in continuous cultures. A second order Haldane-Monod model of continuous cultures is used as a basis for study of the effects of the adjustment of pH by the addition of acidic (or basic) materials. The treatment of a hydrogen ion concentration, in addition to substrate and microbial concentrations as state variables, results in a third order system of equations describing the process. The analysis of the system in equilibrium yields several admissible steady states, that is, steady states which satisfy all constraints. An optimal control problem is formulated and subsequently solved to maximize steady-state microbial production."}
{"id": "PMID:3238", "title": "Preparation and properties of soluble-insoluble nicotinamide coenzymes.", "content": "A soluble-insoluble form of nicotinamide adenine dinucleotide (NAD+), which can be rendered either soluble or insoluble by simply adjusting the pH, has been prepared by covalently coupling NAD to alginic acid using 1,2,7,8-diepoxyoctane. The NAD bound to the alginic acid showed the coenzymic function in the soluble state and could be collected for further use as precipitate by lowering the pH to below 3. Coupling soluble-insoluble coenzymes with insolubilized apoenzymes is possible in fluidized and fixed-bed reactors.", "contents": "Preparation and properties of soluble-insoluble nicotinamide coenzymes. A soluble-insoluble form of nicotinamide adenine dinucleotide (NAD+), which can be rendered either soluble or insoluble by simply adjusting the pH, has been prepared by covalently coupling NAD to alginic acid using 1,2,7,8-diepoxyoctane. The NAD bound to the alginic acid showed the coenzymic function in the soluble state and could be collected for further use as precipitate by lowering the pH to below 3. Coupling soluble-insoluble coenzymes with insolubilized apoenzymes is possible in fluidized and fixed-bed reactors."}
{"id": "PMID:3240", "title": "Studies on some lipogenic enzymes of cultured myeloid leukemic cells.", "content": "The microsomal fraction of M1 cells (an established cell line of myeloid leukemia) was capable of catalyzing acylation of sn-glycerol 3-phosphate by long-chain fatty acyl-CoA thioesters. The principal lipid product formed was identified as phosphatidic acid. Palmityl-CoA, stearyl-CoA, and oleyl-CoA were more effective acyl donors than linoleyl-CoA and arachidonyl-CoA. M1 cells and macrophages differentiated from them exhibited similar levels of sn-glycerol 3-phosphate-acylating activity, which were approximately one-half that in mouse liver and approximately four times that in peritoneal macrophages. The levels of acetyl-CoA carboxylase activity in M1 cells and macrophages differentiated from them were not significantly different from each other and were comparable to those in mouse liver, whereas no activity was detected in peritoneal macrophages. These results indicated that differentiation of the myeloid leukemic cells, which results in loss of leukemogenicity and mitotic activity, is not associated with changes in the activities of these lipogenic enzymes, although the cultured cells exhibited remarkably higher activities than freshly harvested peritoneal macrophages. Furthermore, the present study supports the view that the glycerophosphate pathway makes an essential contribution to the de novo synthesis of phospholipids in M1 cells, as well as in both types of macrophages.", "contents": "Studies on some lipogenic enzymes of cultured myeloid leukemic cells. The microsomal fraction of M1 cells (an established cell line of myeloid leukemia) was capable of catalyzing acylation of sn-glycerol 3-phosphate by long-chain fatty acyl-CoA thioesters. The principal lipid product formed was identified as phosphatidic acid. Palmityl-CoA, stearyl-CoA, and oleyl-CoA were more effective acyl donors than linoleyl-CoA and arachidonyl-CoA. M1 cells and macrophages differentiated from them exhibited similar levels of sn-glycerol 3-phosphate-acylating activity, which were approximately one-half that in mouse liver and approximately four times that in peritoneal macrophages. The levels of acetyl-CoA carboxylase activity in M1 cells and macrophages differentiated from them were not significantly different from each other and were comparable to those in mouse liver, whereas no activity was detected in peritoneal macrophages. These results indicated that differentiation of the myeloid leukemic cells, which results in loss of leukemogenicity and mitotic activity, is not associated with changes in the activities of these lipogenic enzymes, although the cultured cells exhibited remarkably higher activities than freshly harvested peritoneal macrophages. Furthermore, the present study supports the view that the glycerophosphate pathway makes an essential contribution to the de novo synthesis of phospholipids in M1 cells, as well as in both types of macrophages."}
{"id": "PMID:3245", "title": "Impairment in the hepatic clearance of (35S)-bromosulphophthalein in paracetamol-intoxicated rats.", "content": "1 The overall functional capacity of the liver was evaluated using [35S]-bromosulphophthalein (BSP, 100 mg/kg, i.v.) in biliary fistulated adult rats pretreated orally with different doses of paracetamol (APAP) for varying time intervals. 2 The maximal hepatic damage occurred between 12-18 h after single doses of APAP (0.5 or 1 g/kg); hepatic excretory function returned to control levels by 48-72 hours. 3 Administration of either 0.5 or 1 g/kg APAP 18 h before BSP caused a dose-dependent inhibition of the choleretic effect of BSP and of the 60 min cumulative excretion of the dye, but conversely, produced a significant increase in the liver and plasma concentrations of 35S. 4 Following acute (0.25 g/kg), or subacute (0.5 g/kg, twice daily for 7 days) treatment with APAP, the total excretion of 35S in bile and the retention of 35S in the liver or plasma remained essentially the same as that for the controls. 5 In rats given single doses of 1 g/kg APAP, the hepatic uptake of the dye was significantly increased during the early stages of intoxication, while the opposite effect was observed at late periods. 6 The bile flow appeared to be inversely related to the excretion of unchanged BSP, and directly related to the excretion of the major BSP conjugate in bile. 7 The hepatic clearance of BSP was more rapid in rats treated subacutely with 0.5 or 1 g/kg APAP, than in those treated acutely with equal doses, suggesting that the intensity of APAP-induced hepatotoxicity became less severe after the repeated administration of this drug. 8 It is concluded that the hepatic uptake, metabolism and excretion of BSP are reversibly impaired following APAP-induced liver injury.", "contents": "Impairment in the hepatic clearance of (35S)-bromosulphophthalein in paracetamol-intoxicated rats. 1 The overall functional capacity of the liver was evaluated using [35S]-bromosulphophthalein (BSP, 100 mg/kg, i.v.) in biliary fistulated adult rats pretreated orally with different doses of paracetamol (APAP) for varying time intervals. 2 The maximal hepatic damage occurred between 12-18 h after single doses of APAP (0.5 or 1 g/kg); hepatic excretory function returned to control levels by 48-72 hours. 3 Administration of either 0.5 or 1 g/kg APAP 18 h before BSP caused a dose-dependent inhibition of the choleretic effect of BSP and of the 60 min cumulative excretion of the dye, but conversely, produced a significant increase in the liver and plasma concentrations of 35S. 4 Following acute (0.25 g/kg), or subacute (0.5 g/kg, twice daily for 7 days) treatment with APAP, the total excretion of 35S in bile and the retention of 35S in the liver or plasma remained essentially the same as that for the controls. 5 In rats given single doses of 1 g/kg APAP, the hepatic uptake of the dye was significantly increased during the early stages of intoxication, while the opposite effect was observed at late periods. 6 The bile flow appeared to be inversely related to the excretion of unchanged BSP, and directly related to the excretion of the major BSP conjugate in bile. 7 The hepatic clearance of BSP was more rapid in rats treated subacutely with 0.5 or 1 g/kg APAP, than in those treated acutely with equal doses, suggesting that the intensity of APAP-induced hepatotoxicity became less severe after the repeated administration of this drug. 8 It is concluded that the hepatic uptake, metabolism and excretion of BSP are reversibly impaired following APAP-induced liver injury."}
{"id": "PMID:3246", "title": "Dual effect of alpha-adrenoceptor antagonists in rat isolated vas deferens.", "content": "1 In rat isolated vas deferens, the isotonic contractile responses to low doses of noradrenaline or adrenaline were antagonized, and those to high doses were potentiated, by yohimbine, piperoxan, phentolamine and tolazoline. Effects due to intermediate doses were not affected, or were potentiated within about 30 min, following an initial inhibition. 2 The alpha-adrenoceptor blockers thus caused a shift to the right and an increase of the maximum height of log dose-response curves of alpha-adrenoceptor stimulants. For a given dose of antagonist, the onset was slower for the potentiating than for the blocking effect. 3 The shift to the right induced by piperoxan and yohimbine on dose-response curves of noradrenaline and adrenaline was analysed with the Schild plot, and the slopes obtained, around 0.3, were lower than expected from receptor theory. When cocaine was used to block neuronal uptake, the slopes were close to 1.0. 4 The increase in maximum response to noradrenaline and adrenaline induced by alpha-adrenoceptor blockers was dependent on the time of incubation, on the dose of antagonist, and on the initial height of responses to the agonist. A less pronounced potentiation was also obtained when acetylcholine was used as agonist. 5 The findings are explained in terms of receptor theory as being due to a dual effect of alpha-adrenoceptor antagonists; competitive antagonism proper, which may be disclosed after blockade of neuronal uptake, and an interaction at a different locus, which results in potentiation of the effects of noradrenaline and adrenaline.", "contents": "Dual effect of alpha-adrenoceptor antagonists in rat isolated vas deferens. 1 In rat isolated vas deferens, the isotonic contractile responses to low doses of noradrenaline or adrenaline were antagonized, and those to high doses were potentiated, by yohimbine, piperoxan, phentolamine and tolazoline. Effects due to intermediate doses were not affected, or were potentiated within about 30 min, following an initial inhibition. 2 The alpha-adrenoceptor blockers thus caused a shift to the right and an increase of the maximum height of log dose-response curves of alpha-adrenoceptor stimulants. For a given dose of antagonist, the onset was slower for the potentiating than for the blocking effect. 3 The shift to the right induced by piperoxan and yohimbine on dose-response curves of noradrenaline and adrenaline was analysed with the Schild plot, and the slopes obtained, around 0.3, were lower than expected from receptor theory. When cocaine was used to block neuronal uptake, the slopes were close to 1.0. 4 The increase in maximum response to noradrenaline and adrenaline induced by alpha-adrenoceptor blockers was dependent on the time of incubation, on the dose of antagonist, and on the initial height of responses to the agonist. A less pronounced potentiation was also obtained when acetylcholine was used as agonist. 5 The findings are explained in terms of receptor theory as being due to a dual effect of alpha-adrenoceptor antagonists; competitive antagonism proper, which may be disclosed after blockade of neuronal uptake, and an interaction at a different locus, which results in potentiation of the effects of noradrenaline and adrenaline."}
{"id": "PMID:3242", "title": "[Isotopic study of fluid and electrolyte disturbances in decompensated chronic respiratory insufficiency (author's transl)].", "content": "The study of fluid and electrolyte disturbances by isotope radiodilution method is carried out in 22 patients with chronic respiratory insufficiency and cardiac failure. The simultaneous measurements of hydro-ionic compartments have been carried out with tritiated water (HTO), labelled sodium (22Na), labelled potassium (42K) and labelled bromine (82Br). From these measurements, the various water spaces are calculated: total water (ET) and extracellular fluids (LEC), also exchangeable electrolytes: sodium (NaE), potassium (KE), chlorine (ClE) and derived values. Results are compared to corresponding values in controls with the same obesity index. Patients with respiratory insufficiency show a fluid and sodium rise, similar to that found in cardiac failure and denutrition. The (NaE + KE)/ET ratio is not significantly decreased and the natremia is only slightly lower. There is no real potassium depletion in most patients.", "contents": "[Isotopic study of fluid and electrolyte disturbances in decompensated chronic respiratory insufficiency (author's transl)]. The study of fluid and electrolyte disturbances by isotope radiodilution method is carried out in 22 patients with chronic respiratory insufficiency and cardiac failure. The simultaneous measurements of hydro-ionic compartments have been carried out with tritiated water (HTO), labelled sodium (22Na), labelled potassium (42K) and labelled bromine (82Br). From these measurements, the various water spaces are calculated: total water (ET) and extracellular fluids (LEC), also exchangeable electrolytes: sodium (NaE), potassium (KE), chlorine (ClE) and derived values. Results are compared to corresponding values in controls with the same obesity index. Patients with respiratory insufficiency show a fluid and sodium rise, similar to that found in cardiac failure and denutrition. The (NaE + KE)/ET ratio is not significantly decreased and the natremia is only slightly lower. There is no real potassium depletion in most patients."}
{"id": "PMID:3241", "title": "[Role of P50 in resuscitation (author's transl)].", "content": "The amount of oxygen made available to the tissues of the body depends essentially upon pulmonary gas exchanges, cardiac output and its regional distribution, haemoglobin concentration and also upon the oxygen affinity of the haemoglobin molecule. That a standard oxyhaemoglobin dissociation curve faithfully describes oxygen loading and unloading both in healthy subjects and in those suffering from pathological process has come under attack. Beside the effect of pH, PCO2 and temperature, the oxyhaemoglobin dissociation curve can be modified by alterations of other factors (concentration of 2,3-diphosphoglycerate, hormones, drugs). Although the shifts of the oxyhaemoglobin dissociation curve, expressed by variations of P50 may seem minute, the effect of these shifts, expressed in terms of the \"functional value of haemoglobin\" are very large. Assessment of the intensive care patient must take into account the effect of alterations of the oxyhaemoglobin dissociation curve which can either increase or diminish tissue oxygenation.", "contents": "[Role of P50 in resuscitation (author's transl)]. The amount of oxygen made available to the tissues of the body depends essentially upon pulmonary gas exchanges, cardiac output and its regional distribution, haemoglobin concentration and also upon the oxygen affinity of the haemoglobin molecule. That a standard oxyhaemoglobin dissociation curve faithfully describes oxygen loading and unloading both in healthy subjects and in those suffering from pathological process has come under attack. Beside the effect of pH, PCO2 and temperature, the oxyhaemoglobin dissociation curve can be modified by alterations of other factors (concentration of 2,3-diphosphoglycerate, hormones, drugs). Although the shifts of the oxyhaemoglobin dissociation curve, expressed by variations of P50 may seem minute, the effect of these shifts, expressed in terms of the \"functional value of haemoglobin\" are very large. Assessment of the intensive care patient must take into account the effect of alterations of the oxyhaemoglobin dissociation curve which can either increase or diminish tissue oxygenation."}
{"id": "PMID:3243", "title": "[Acid-base disorders in status asthmaticus (author's transl)].", "content": "In 85 patinets withstatus asthmaticus, the authors have studied the acid-base balance, the blood gas tensions and various humoral parameters. The values were classified into two groups according to the PaCO2 level: below or equal to 44 torr (Group I), higher than 44 torr (Group II). In the 58 cases of Group II, there was a very close positive correlation between PaCO2 and H + ions, practically the same as that established by BRACKETT et al. [3] in experimental acute hypercapnia in man. On the contrary, the correlation derived from cases of status asthmaticus in the literature showed, in some cases, a metabolic component in acidosis. In the present work, the mean value of lactates was close to normal; there was a slow increase in protein content and hematocrit, in the two groups. The prognosis of the status asthmaticus depends on the degrees of hypercapnia: when it reaches 70 torr, mechanical ventilation is urgently needed and is the main part of the treatment; the use of additional drugs remains a matter of specific case.", "contents": "[Acid-base disorders in status asthmaticus (author's transl)]. In 85 patinets withstatus asthmaticus, the authors have studied the acid-base balance, the blood gas tensions and various humoral parameters. The values were classified into two groups according to the PaCO2 level: below or equal to 44 torr (Group I), higher than 44 torr (Group II). In the 58 cases of Group II, there was a very close positive correlation between PaCO2 and H + ions, practically the same as that established by BRACKETT et al. [3] in experimental acute hypercapnia in man. On the contrary, the correlation derived from cases of status asthmaticus in the literature showed, in some cases, a metabolic component in acidosis. In the present work, the mean value of lactates was close to normal; there was a slow increase in protein content and hematocrit, in the two groups. The prognosis of the status asthmaticus depends on the degrees of hypercapnia: when it reaches 70 torr, mechanical ventilation is urgently needed and is the main part of the treatment; the use of additional drugs remains a matter of specific case."}
{"id": "PMID:3247", "title": "The evaluation of the novel pressor activity of gamma-piperidinobutyramide (WY 20051, DF480).", "content": "1 gamma-Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 x 10(-6)-3.0 x 10(-4) mol/kg. 2 High doses (greater than 3.8 x 10(-5) mol/kg) or even repeated submaximal doses (1.9 x 10(-5) mol/kg) of Wy 20051 caused tachyphylaxis of this pressor response. 3 The noradrenaline pressor-response curve was shifted significantly to the right of the control curve following a dose of Wy 20051 (1.5 x 10(-4) mol/kg cumulative). 4 The dose-response curve for the pressor action of Wy 20051 was potentiated in reserpine-treated anaesthetized rats. In contrast, tyramine-induced pressor responses were abolished. 5 Wy 20051 contracted the guinea-pig isolated aortic spiral preparation (3.8 x 10(-5)-6.0 x 10(-4) mol) and evoked constrictor responses in the perfused mesenteric vasculature preparation of the rat (5.9 x 10(-7)-1.2 x 10(-5) mol). At higher doses the responses were reduced. 6 Wy 20051-induced constrictor responses of the perfused mesentery were unaffected by blockade of alpha-adrenoceptors or by tachyphylaxis of 5-hydroxytryptamine receptors. 7 The time for abolition of Wy 20051-induced constrictor responses of the mesentery in a calcium-free medium was not significantly different from that required for noradrenaline, but was significantly greater than that for KCl (P less than 0.001). 8 Wy 20051 and noradrenaline, but not KCl, evoked constrictor responses in the depolarized rat mesenteric vasculature. 9 The results indicate that Wy 20051 evokes pressor responses which have some of the characteristics of those of noradrenaline. However, the responses are not elicited by an alpha-adrenoceptor mechanism.", "contents": "The evaluation of the novel pressor activity of gamma-piperidinobutyramide (WY 20051, DF480). 1 gamma-Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 x 10(-6)-3.0 x 10(-4) mol/kg. 2 High doses (greater than 3.8 x 10(-5) mol/kg) or even repeated submaximal doses (1.9 x 10(-5) mol/kg) of Wy 20051 caused tachyphylaxis of this pressor response. 3 The noradrenaline pressor-response curve was shifted significantly to the right of the control curve following a dose of Wy 20051 (1.5 x 10(-4) mol/kg cumulative). 4 The dose-response curve for the pressor action of Wy 20051 was potentiated in reserpine-treated anaesthetized rats. In contrast, tyramine-induced pressor responses were abolished. 5 Wy 20051 contracted the guinea-pig isolated aortic spiral preparation (3.8 x 10(-5)-6.0 x 10(-4) mol) and evoked constrictor responses in the perfused mesenteric vasculature preparation of the rat (5.9 x 10(-7)-1.2 x 10(-5) mol). At higher doses the responses were reduced. 6 Wy 20051-induced constrictor responses of the perfused mesentery were unaffected by blockade of alpha-adrenoceptors or by tachyphylaxis of 5-hydroxytryptamine receptors. 7 The time for abolition of Wy 20051-induced constrictor responses of the mesentery in a calcium-free medium was not significantly different from that required for noradrenaline, but was significantly greater than that for KCl (P less than 0.001). 8 Wy 20051 and noradrenaline, but not KCl, evoked constrictor responses in the depolarized rat mesenteric vasculature. 9 The results indicate that Wy 20051 evokes pressor responses which have some of the characteristics of those of noradrenaline. However, the responses are not elicited by an alpha-adrenoceptor mechanism."}
{"id": "PMID:3248", "title": "Electroconvulsive shock increases the behavioural responses of rats to brain 5-hydroxytryptamine accumulation and central nervous system stimulant drugs.", "content": "1 A single electroconvulsive shock (ECS) of 150 V for 1 s increased the concentration of rat brain 5-hydroxyindoleacetic acid (5-HIAA) but did not alter brain 5-hydroxytryptamine (5-HT) or tryptophan concentrations 3 h later. 2 A single ECS decreased 5-HT synthesis 3 h and 6 h later. Synthesis was back to normal after 24 hours. The ECS-treated rats did not show greater hyperactivity produced by the increased brain 5-HT accumulation following administration of L-tryptophan and tranylcypromine at any time up to 24 h later. This suggests that a single electroshock does not alter 5-HT functional activity. 3 Twenty-four hours after the final ECS of a series of 10 shocks given once daily, the rats were given tranylcypromine and L-tryptophan. They displayed greater hyperactivity than control rats not treated with ECS, suggesting that ECS increases 5-HT functional activity. Brain concentrations of 5-HT, 5-HIAA and tryptophan were then unchanged by ECS. 5-HT synthesis and accumulation of 5-HT following tranylcypromine and L-tryptophan were not altered by ECS. 4 The hyperactivity following administration of the 5-HT agonist 5-methoxy N,N-dimethyltryptamine was enhanced by repeated (10 day) ECS, suggesting altered post-synaptic responses to 5-HT receptor stimulation. 5 Repeated ECS enhanced locomotor activity following tranylcypromine and L-DOPA. It did not alter brain noradrenaline or dopamine concentrations. 6 The latent period before a pentylenetetrazol-induced convulsion was shortened by repeated ECS. 7 Following repeated ECS there appears to be increased neuronal sensitivity to certain stimuli producing centrally mediated behavioural stimulation. This is discussed in relation to the mechanism by which electroconvulsive therapy (ECT) produces its therapeutic effect.", "contents": "Electroconvulsive shock increases the behavioural responses of rats to brain 5-hydroxytryptamine accumulation and central nervous system stimulant drugs. 1 A single electroconvulsive shock (ECS) of 150 V for 1 s increased the concentration of rat brain 5-hydroxyindoleacetic acid (5-HIAA) but did not alter brain 5-hydroxytryptamine (5-HT) or tryptophan concentrations 3 h later. 2 A single ECS decreased 5-HT synthesis 3 h and 6 h later. Synthesis was back to normal after 24 hours. The ECS-treated rats did not show greater hyperactivity produced by the increased brain 5-HT accumulation following administration of L-tryptophan and tranylcypromine at any time up to 24 h later. This suggests that a single electroshock does not alter 5-HT functional activity. 3 Twenty-four hours after the final ECS of a series of 10 shocks given once daily, the rats were given tranylcypromine and L-tryptophan. They displayed greater hyperactivity than control rats not treated with ECS, suggesting that ECS increases 5-HT functional activity. Brain concentrations of 5-HT, 5-HIAA and tryptophan were then unchanged by ECS. 5-HT synthesis and accumulation of 5-HT following tranylcypromine and L-tryptophan were not altered by ECS. 4 The hyperactivity following administration of the 5-HT agonist 5-methoxy N,N-dimethyltryptamine was enhanced by repeated (10 day) ECS, suggesting altered post-synaptic responses to 5-HT receptor stimulation. 5 Repeated ECS enhanced locomotor activity following tranylcypromine and L-DOPA. It did not alter brain noradrenaline or dopamine concentrations. 6 The latent period before a pentylenetetrazol-induced convulsion was shortened by repeated ECS. 7 Following repeated ECS there appears to be increased neuronal sensitivity to certain stimuli producing centrally mediated behavioural stimulation. This is discussed in relation to the mechanism by which electroconvulsive therapy (ECT) produces its therapeutic effect."}
{"id": "PMID:3249", "title": "Effects of chronic nicotine administration on the denervated rat adrenal medulla.", "content": "1 The effects of chronic nicotine administration (1 or 10 mg/kg, s.c., twice daily) were studied in intact and denervated rat adrenal glands to determine the relative roles of central input and direct actions on catecholamines. 2 Catecholamine depletion was obtained in the intact glands from 1-7 days of treatment with 10 mg/kg, with recovery by 14 days of treatment; catecholamines were not decreased in denervated adrenal glands. 3 Catecholamine depletion was accompanied by a decline in functional storage vesicles (determined by [3H]-adrenaline uptake per gland) in the intact side, while no change was seen in the denervated side; the proportion of newly synthesized vesicles increased markedly during 1-7 days of treatment with 10 mg/kg in the intact side, while a much smaller increase of shorter duration was seen in the denervated adrenal gland. 4 Chronic nicotine administration at either dose level induced tyrosine hydroxylase in both intact and denervated glands, but the increase occurred more slowly in the denervated glands. 5 Dopamine beta-hydroxylase levels increased similarly in both sides during treatment with nicotine (10 mg/kg). 6 These studies suggest that although long-term adrenal denervation eliminates the catecholamine depletion caused by chronic administration of nicotine, the mechanisms for induction of catecholamine synthesizing enzymes are still capable of responding to the drug.", "contents": "Effects of chronic nicotine administration on the denervated rat adrenal medulla. 1 The effects of chronic nicotine administration (1 or 10 mg/kg, s.c., twice daily) were studied in intact and denervated rat adrenal glands to determine the relative roles of central input and direct actions on catecholamines. 2 Catecholamine depletion was obtained in the intact glands from 1-7 days of treatment with 10 mg/kg, with recovery by 14 days of treatment; catecholamines were not decreased in denervated adrenal glands. 3 Catecholamine depletion was accompanied by a decline in functional storage vesicles (determined by [3H]-adrenaline uptake per gland) in the intact side, while no change was seen in the denervated side; the proportion of newly synthesized vesicles increased markedly during 1-7 days of treatment with 10 mg/kg in the intact side, while a much smaller increase of shorter duration was seen in the denervated adrenal gland. 4 Chronic nicotine administration at either dose level induced tyrosine hydroxylase in both intact and denervated glands, but the increase occurred more slowly in the denervated glands. 5 Dopamine beta-hydroxylase levels increased similarly in both sides during treatment with nicotine (10 mg/kg). 6 These studies suggest that although long-term adrenal denervation eliminates the catecholamine depletion caused by chronic administration of nicotine, the mechanisms for induction of catecholamine synthesizing enzymes are still capable of responding to the drug."}
{"id": "PMID:3250", "title": "Catechol O-methyltransferase in red blood cells of schizophrenic, depressed, and normal human subjects.", "content": "Catechol O-methyltransferase of lysed human red blood cells was assayed under optimal conditions, using saturating concentrations of the substrates, S-adenosyl-L-methionine and 3-4-dihydroxybenzoic acid. The mean enzyme activity found in 24 normal subjects was 29-2 nmol/hr/ml RBC. The mean activity in blood of 33 female unipolar depressives was not significantly different from normal. However, higher enzyme activities were observed in the blood of 11 schizophrenic patients (38-9 nmol/hr/ml RBC). Partially purified enzyme preparations from blood of normal and schizophrenic individuals were indistinguishable with respect to substrate specificities, isoelectric pH values, and ratios of the two O-methylated products. Therefore it is unlikely that any defect in O-methylation which may occur in schizophrenia can be attributed to a change in the intrinsic properties of erythrocyte catechol O-methyltransferase.", "contents": "Catechol O-methyltransferase in red blood cells of schizophrenic, depressed, and normal human subjects. Catechol O-methyltransferase of lysed human red blood cells was assayed under optimal conditions, using saturating concentrations of the substrates, S-adenosyl-L-methionine and 3-4-dihydroxybenzoic acid. The mean enzyme activity found in 24 normal subjects was 29-2 nmol/hr/ml RBC. The mean activity in blood of 33 female unipolar depressives was not significantly different from normal. However, higher enzyme activities were observed in the blood of 11 schizophrenic patients (38-9 nmol/hr/ml RBC). Partially purified enzyme preparations from blood of normal and schizophrenic individuals were indistinguishable with respect to substrate specificities, isoelectric pH values, and ratios of the two O-methylated products. Therefore it is unlikely that any defect in O-methylation which may occur in schizophrenia can be attributed to a change in the intrinsic properties of erythrocyte catechol O-methyltransferase."}
{"id": "PMID:3251", "title": "The expectation of outcome from maintenance therapy in chronic schizophrenic patients.", "content": "The results from a prospective follow-up study of a group of schizophrenic patients suggest that a significant proportion (41 per cent) are likely to relapse during a two-year period despite the prescription of long-acting injectable neuroleptic drugs. Some will relapse because of a failure of the regime, but others (32-37 per cent) because the pharmacological protection of these drugs would appear to be less effective in certain patients. Even with the major advantages of the long-acting injectable neuroleptics over oral medication, the schizophrenic patient population remains a group with a high incidence of psychiatric and social morbidity which continues to require the full resources of both the hospital and community services.", "contents": "The expectation of outcome from maintenance therapy in chronic schizophrenic patients. The results from a prospective follow-up study of a group of schizophrenic patients suggest that a significant proportion (41 per cent) are likely to relapse during a two-year period despite the prescription of long-acting injectable neuroleptic drugs. Some will relapse because of a failure of the regime, but others (32-37 per cent) because the pharmacological protection of these drugs would appear to be less effective in certain patients. Even with the major advantages of the long-acting injectable neuroleptics over oral medication, the schizophrenic patient population remains a group with a high incidence of psychiatric and social morbidity which continues to require the full resources of both the hospital and community services."}
{"id": "PMID:3258", "title": "Salicylates and renal function in rheumatoid arthritis.", "content": "The effect of salicylate treatment on the kidney, particularly medullary function, was investigated. In a retrospective analysis patients with rheumatoid arthritis (RA) treated with high doses of salicylates were shown to have inferior urinary concentrating power and increased excretion of N-acetyl-beta-D-glucosaminidase (NAG) when compared with patients who had not received salicylate treatment. A prospective study of renal funcition in healthy people and patients with RA starting salicylate in therapeutic doses showed that while epithelial cell excretion was only transiently raised in both groups the excretion of NAG was increased in all cases at three days and this increase was sustained at 10 days, all values being much higher in the patients than in the healthy subjects. Thus salicylate treatment does cause renal tubular damage but this damage results in only minimal impairment of function and does not constitute a reason for withholding salicylate treatment.", "contents": "Salicylates and renal function in rheumatoid arthritis. The effect of salicylate treatment on the kidney, particularly medullary function, was investigated. In a retrospective analysis patients with rheumatoid arthritis (RA) treated with high doses of salicylates were shown to have inferior urinary concentrating power and increased excretion of N-acetyl-beta-D-glucosaminidase (NAG) when compared with patients who had not received salicylate treatment. A prospective study of renal funcition in healthy people and patients with RA starting salicylate in therapeutic doses showed that while epithelial cell excretion was only transiently raised in both groups the excretion of NAG was increased in all cases at three days and this increase was sustained at 10 days, all values being much higher in the patients than in the healthy subjects. Thus salicylate treatment does cause renal tubular damage but this damage results in only minimal impairment of function and does not constitute a reason for withholding salicylate treatment."}
{"id": "PMID:3259", "title": "Benzodiazepine drugs in general medical patients.", "content": "Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients.", "contents": "Benzodiazepine drugs in general medical patients. Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients."}
{"id": "PMID:3261", "title": "Decrease of uptake and exchange of neurotransmitter amino acids after depletion of their synaptosomal pools.", "content": "Synaptosomes prelabeled at 37 degrees C with radioactive amino acids (GABA, glutamate, glycine, taurine, alpha-aminoisobutyric acid, phenylalanine, leucine) and then washed at 0 degrees C on Millipore filters (DAWP 02500) lost 60-70% of the accumulated radioactivity. The loss was similar with exogenous tritiated GABA and glutamate, and with [14C]GABA and [14C]glutamate metabolically derived from [14C]glucose. In contrast, radioactive norepinephrine, dopamine and 5-hydroxytryptamine were almost totally retained by cold shocked synaptosomes. After pretreatment with reserpine and nialamide the loss of norepinephrine became significantly greater (about 25%). The uptake of radioactive GABA, glutamate and clycine after cold shock was about 50% reduced, whereas that of radioactive biogenic amines was less affected (reduction of 22% for norepinephrine, 29% for 5-hydroxytryptamine and 35% for dopamine). The loss of amino acids and the reduction of uptake could be minimized by performing the cold shock in hypertonic conditions. In synaptosomes prelabeled with [3H]GABA, a good correlation was observed among magnitude of amino acid pool depletion induced by cold shock or by 56 mM KCl, decrease of subsequent accumulation of [14C]GABA, and decrease of [14C]-GABA-stimulated [3H]GABA release (homoexchange).", "contents": "Decrease of uptake and exchange of neurotransmitter amino acids after depletion of their synaptosomal pools. Synaptosomes prelabeled at 37 degrees C with radioactive amino acids (GABA, glutamate, glycine, taurine, alpha-aminoisobutyric acid, phenylalanine, leucine) and then washed at 0 degrees C on Millipore filters (DAWP 02500) lost 60-70% of the accumulated radioactivity. The loss was similar with exogenous tritiated GABA and glutamate, and with [14C]GABA and [14C]glutamate metabolically derived from [14C]glucose. In contrast, radioactive norepinephrine, dopamine and 5-hydroxytryptamine were almost totally retained by cold shocked synaptosomes. After pretreatment with reserpine and nialamide the loss of norepinephrine became significantly greater (about 25%). The uptake of radioactive GABA, glutamate and clycine after cold shock was about 50% reduced, whereas that of radioactive biogenic amines was less affected (reduction of 22% for norepinephrine, 29% for 5-hydroxytryptamine and 35% for dopamine). The loss of amino acids and the reduction of uptake could be minimized by performing the cold shock in hypertonic conditions. In synaptosomes prelabeled with [3H]GABA, a good correlation was observed among magnitude of amino acid pool depletion induced by cold shock or by 56 mM KCl, decrease of subsequent accumulation of [14C]GABA, and decrease of [14C]-GABA-stimulated [3H]GABA release (homoexchange)."}
{"id": "PMID:3263", "title": "Ultrastructural hypoxic changes in Ammon's horn and Purkinje cells.", "content": "Guinea pigs were exposed for varying periods to different degrees of hypoxia by respiration of controlled mixtures of O2-N2 and the CNS subjected to both light and electron microscopic examination after aldehyde fixation by perfusion. The subacute anoxia experiments revealed an alteration in the rough endoplasmic reticulum of the Purkinje cells consisting of the formation of 'paired cisternae'. In the chronic anoxia experiments, small ultrastructural alterations of the same cells were found in association with the appearance of monoparticulate glycogen. The authors debate the significance of these ultrastructural alterations in relation to the damage found in other organs.", "contents": "Ultrastructural hypoxic changes in Ammon's horn and Purkinje cells. Guinea pigs were exposed for varying periods to different degrees of hypoxia by respiration of controlled mixtures of O2-N2 and the CNS subjected to both light and electron microscopic examination after aldehyde fixation by perfusion. The subacute anoxia experiments revealed an alteration in the rough endoplasmic reticulum of the Purkinje cells consisting of the formation of 'paired cisternae'. In the chronic anoxia experiments, small ultrastructural alterations of the same cells were found in association with the appearance of monoparticulate glycogen. The authors debate the significance of these ultrastructural alterations in relation to the damage found in other organs."}
{"id": "PMID:3264", "title": "The effect of taget organ removal on the development of sympathetic neurons.", "content": "The role of target organs in the maturation of adrenergic neurons was studied in the neonatal rat. The superior cervical ganglion (SCG) and its end organs, the salivary glands and iris were employed as a model system. Unilateral sialectomy and iridectomy in 3-day-old animals prevented the normal development of ganglion tyrosine hydroxylase (T-OH) and DOPA decarboxylase activities. These enzymes are highly localized to adrenergic neurons in the SCG, and were used to monitor maturation of these cells. Enzyme activity remained depressed for at least two months, the longest time tested. In contrast, total ganglion protein, a measure of ganglion growth as a whole, initially developed normally. Six weeks after surgery, however, protein content was significantly lower in ganglia deprived of the normal field of innervation. Failure of normal enzyme maturation was apparently dependent on removal of ipsilateral end organs only, since bilateral sialectomy exerted no greater effect than unilateral sialectomy. In adults, unilateral sialectomy and iridectomy did not significantly alter ganglion T-OH activity or protein in rats followed up to one month after surgery.", "contents": "The effect of taget organ removal on the development of sympathetic neurons. The role of target organs in the maturation of adrenergic neurons was studied in the neonatal rat. The superior cervical ganglion (SCG) and its end organs, the salivary glands and iris were employed as a model system. Unilateral sialectomy and iridectomy in 3-day-old animals prevented the normal development of ganglion tyrosine hydroxylase (T-OH) and DOPA decarboxylase activities. These enzymes are highly localized to adrenergic neurons in the SCG, and were used to monitor maturation of these cells. Enzyme activity remained depressed for at least two months, the longest time tested. In contrast, total ganglion protein, a measure of ganglion growth as a whole, initially developed normally. Six weeks after surgery, however, protein content was significantly lower in ganglia deprived of the normal field of innervation. Failure of normal enzyme maturation was apparently dependent on removal of ipsilateral end organs only, since bilateral sialectomy exerted no greater effect than unilateral sialectomy. In adults, unilateral sialectomy and iridectomy did not significantly alter ganglion T-OH activity or protein in rats followed up to one month after surgery."}
{"id": "PMID:3265", "title": "Sensitization and habituation of the plantar cushion reflex in cats.", "content": "The plantar cushion reflex in cats was examined as a model system in a mammal for the study of the effects of repeated stimulation on neural transmission. Effects of various frequencies and intensities of stimulation were similar to those seen in other reflex systems. For instance, for a fixed number of stimuli, habituation of the plantar cushion reflex was more marked at 10 Hz than at 2.0 Hz, and with 1.0 X threshold stimulation than with 5.0 X threshold stimulation. Sensitization occurred at intermediate intensities and frequencies of stimulation. Dorsal root potentials were studied; changes in dorsal root potentials during iterated stimulation did not correlate with the changes in the plantar cushion reflex. These changes in the plantar cushion reflex were also unrelated to variations in afferent transmission peripheral to the spinal cord. Sensitization and habituation in the plantar cushion reflex occurred during iterated stimulation, were produced centrally, and were unrelated to mechanisms of presynaptic inhibition.", "contents": "Sensitization and habituation of the plantar cushion reflex in cats. The plantar cushion reflex in cats was examined as a model system in a mammal for the study of the effects of repeated stimulation on neural transmission. Effects of various frequencies and intensities of stimulation were similar to those seen in other reflex systems. For instance, for a fixed number of stimuli, habituation of the plantar cushion reflex was more marked at 10 Hz than at 2.0 Hz, and with 1.0 X threshold stimulation than with 5.0 X threshold stimulation. Sensitization occurred at intermediate intensities and frequencies of stimulation. Dorsal root potentials were studied; changes in dorsal root potentials during iterated stimulation did not correlate with the changes in the plantar cushion reflex. These changes in the plantar cushion reflex were also unrelated to variations in afferent transmission peripheral to the spinal cord. Sensitization and habituation in the plantar cushion reflex occurred during iterated stimulation, were produced centrally, and were unrelated to mechanisms of presynaptic inhibition."}
{"id": "PMID:3266", "title": "Quantitative localization of tyrosine hydroxylase, dopamine-beta-hydroxylase, phenolethanolamine-N-methyl transferase, and glutamic acid decarboxylase in spinal cord.", "content": "Sensitive radiometric assays for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyl transferase (PNMT), and glutamic acid decarboxylase (GAD) have been combined with microdissection techniques for quantitative localization of these synthetic enzymes in rabbit spinal cord. TH was present uniformly in gray and white matter. DBH was higher in the lateral horns than in the other gray matter areas, and was not detectable in white matter. PNMT was detectable in gray but not white matter, and was considerably lower in activity than the other catecholamine synthetic enzymes. GAD was higher in the dorsal horns at the cervical and lumbar levels than in other gray matter areas and relatively low in white matter. GAD activity was considerably higher than the catecholamine synthetic enzyme activities. The quantitative localizations are consistent with the qualitative immunohistochemical enzymes maps and distributions of the related putative neurotransmitters.", "contents": "Quantitative localization of tyrosine hydroxylase, dopamine-beta-hydroxylase, phenolethanolamine-N-methyl transferase, and glutamic acid decarboxylase in spinal cord. Sensitive radiometric assays for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyl transferase (PNMT), and glutamic acid decarboxylase (GAD) have been combined with microdissection techniques for quantitative localization of these synthetic enzymes in rabbit spinal cord. TH was present uniformly in gray and white matter. DBH was higher in the lateral horns than in the other gray matter areas, and was not detectable in white matter. PNMT was detectable in gray but not white matter, and was considerably lower in activity than the other catecholamine synthetic enzymes. GAD was higher in the dorsal horns at the cervical and lumbar levels than in other gray matter areas and relatively low in white matter. GAD activity was considerably higher than the catecholamine synthetic enzyme activities. The quantitative localizations are consistent with the qualitative immunohistochemical enzymes maps and distributions of the related putative neurotransmitters."}
{"id": "PMID:3268", "title": "Extraction of a calcium-phospholipid-phosphate complex from bone.", "content": "A calcium-phospholipid-phosphate complex with a constant 1:1 calcium to total phosphate molar ratio is shown to exist in rabbit and calf bone. This complex, which may be involved in the transport and deposition of bone mineral, appears to constitute a significantly greater proportion of the lipids of younger bone than of more mature bone. The comples was isolated by a modified Folch extraction employing ultrasonic disruption of cellular material. Evidence is presented to show that the complex is a natural constituent of bone rather than one created artifactually during extraction.", "contents": "Extraction of a calcium-phospholipid-phosphate complex from bone. A calcium-phospholipid-phosphate complex with a constant 1:1 calcium to total phosphate molar ratio is shown to exist in rabbit and calf bone. This complex, which may be involved in the transport and deposition of bone mineral, appears to constitute a significantly greater proportion of the lipids of younger bone than of more mature bone. The comples was isolated by a modified Folch extraction employing ultrasonic disruption of cellular material. Evidence is presented to show that the complex is a natural constituent of bone rather than one created artifactually during extraction."}
{"id": "PMID:3269", "title": "Magill circuit and controlled ventilation.", "content": "Nine patients under anaesthesia were controlled manually with the Magill attachment. Nine other patients using the same circuit under anaesthesia breathed spontaneously. Blood gases were studied throughout the period of operation to determine the adequacy of ventilation. The results show that the Magill attachment was adequate for controlled ventilation using normal flows (9 1/min) in young healthy patients.", "contents": "Magill circuit and controlled ventilation. Nine patients under anaesthesia were controlled manually with the Magill attachment. Nine other patients using the same circuit under anaesthesia breathed spontaneously. Blood gases were studied throughout the period of operation to determine the adequacy of ventilation. The results show that the Magill attachment was adequate for controlled ventilation using normal flows (9 1/min) in young healthy patients."}
{"id": "PMID:3270", "title": "The reduction of coma time in lipophilic drug overdose using castor oil.", "content": "A clinical trial of castor oil in overdoses of lipophilic drugs gave a strong clinical impression that it was effective in speeding up recovery. Therefore, animal experiments were undertaken to confirm that castor oil acts as a ligand in Ethchlorvynol poisoning and that its use reduces coma time. Serial serum levels of Ethchlorvynol were obtained from dogs given Ethchlorvynol 150 mg/kg alone, and the same dose dissolved in castor oil 15 ml/kg in a crossover fashion. The result was a reduction of peak serum levels and of the half-life of the drug when the castor oil solution was used. In order to mimic the clinical situation more closely, a further crossover study was undertaken using Ethchlorvynol 300 mg/kg alone and the same dose followed by castor oil 15 ml/kg repeated q12h. This showed no delay in reaching peak serum concentration and no reduction of peak levels. However, it did show a 31 per cent reduction in the half-life of the drug. This change is statistically significant, and supports the continued use of castor oil in lipophilic drug overdose.", "contents": "The reduction of coma time in lipophilic drug overdose using castor oil. A clinical trial of castor oil in overdoses of lipophilic drugs gave a strong clinical impression that it was effective in speeding up recovery. Therefore, animal experiments were undertaken to confirm that castor oil acts as a ligand in Ethchlorvynol poisoning and that its use reduces coma time. Serial serum levels of Ethchlorvynol were obtained from dogs given Ethchlorvynol 150 mg/kg alone, and the same dose dissolved in castor oil 15 ml/kg in a crossover fashion. The result was a reduction of peak serum levels and of the half-life of the drug when the castor oil solution was used. In order to mimic the clinical situation more closely, a further crossover study was undertaken using Ethchlorvynol 300 mg/kg alone and the same dose followed by castor oil 15 ml/kg repeated q12h. This showed no delay in reaching peak serum concentration and no reduction of peak levels. However, it did show a 31 per cent reduction in the half-life of the drug. This change is statistically significant, and supports the continued use of castor oil in lipophilic drug overdose."}
{"id": "PMID:3271", "title": "An endogalactosaminidase from Streptomyces griseus.", "content": "An endogalactosaminidase has been purified 34-fold from the culture filtrate of Streptomyces griseus. This enzyme cleaves GalN-GalN linkages in oligogalactosaminoglycan, a galactosamine-rich oligosaccharide isolated from the culture filtrate of a Neurospora mutant. Since some or all of the GalN-GalN bonds in this molecule link positions 1 and 4, and are in the alpha-configuration, we are probably dealing with an endo-alpha-(1 leads to 4)-galactosaminidase, bu this characterization is only tentative because the few bonds cleaved by the enzyme could have a different structure. The enzyme is inactive towards N-acetyl-oligogalactosaminoglycan and chitosan. The endogalactosaminidase preparations also cleave high molecular weight galactosaminoglycan (obtained from Neurospora) into fragments greater than or equal to 10(4) daltons in molecular weight, and catalyze the release of Neurospora sporelings from the glass surfaces to which they are anchored. Galactosaminoglycan-cleaving and sporeling-releasing activities elute jointly from DEAE-cellulose columns. This observation provides further support for an earlier proposal that the sporelings are anchored to the glass by means of galactosaminoglycan molecules.", "contents": "An endogalactosaminidase from Streptomyces griseus. An endogalactosaminidase has been purified 34-fold from the culture filtrate of Streptomyces griseus. This enzyme cleaves GalN-GalN linkages in oligogalactosaminoglycan, a galactosamine-rich oligosaccharide isolated from the culture filtrate of a Neurospora mutant. Since some or all of the GalN-GalN bonds in this molecule link positions 1 and 4, and are in the alpha-configuration, we are probably dealing with an endo-alpha-(1 leads to 4)-galactosaminidase, bu this characterization is only tentative because the few bonds cleaved by the enzyme could have a different structure. The enzyme is inactive towards N-acetyl-oligogalactosaminoglycan and chitosan. The endogalactosaminidase preparations also cleave high molecular weight galactosaminoglycan (obtained from Neurospora) into fragments greater than or equal to 10(4) daltons in molecular weight, and catalyze the release of Neurospora sporelings from the glass surfaces to which they are anchored. Galactosaminoglycan-cleaving and sporeling-releasing activities elute jointly from DEAE-cellulose columns. This observation provides further support for an earlier proposal that the sporelings are anchored to the glass by means of galactosaminoglycan molecules."}
{"id": "PMID:3272", "title": "Fractionation of nucleolar proteins by two-dimensional gel electrphoresis.", "content": "Isolation of nucleolar proteins was obtained by dissociation in the presence of urea-guanidine hydrochloride, followed by high-speed centrifugation to remove nucleic acids. At least 31 fractions of nucleolar proteins were detected by isoelectrofocusing gel electrophoresis in pH range 3.5-10. Following two-dimensional gel electrophoresis on sodium dodecyl sulfate-polyacrylamide slab gels, more than 100 components of nucleolar proteins were identifieid. Two-thirds of nucleolar proteins were located in the pH range 5-8 following isoelectrofocusing. The molecular weights of these classes of proteins were shown to be mostly 30000-70000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.", "contents": "Fractionation of nucleolar proteins by two-dimensional gel electrphoresis. Isolation of nucleolar proteins was obtained by dissociation in the presence of urea-guanidine hydrochloride, followed by high-speed centrifugation to remove nucleic acids. At least 31 fractions of nucleolar proteins were detected by isoelectrofocusing gel electrophoresis in pH range 3.5-10. Following two-dimensional gel electrophoresis on sodium dodecyl sulfate-polyacrylamide slab gels, more than 100 components of nucleolar proteins were identifieid. Two-thirds of nucleolar proteins were located in the pH range 5-8 following isoelectrofocusing. The molecular weights of these classes of proteins were shown to be mostly 30000-70000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis."}
{"id": "PMID:3273", "title": "Temperature-induced alanine oxidation in a psychrotrophic Pseudomonas.", "content": "A psychrotrophic pseudomonad isolated from iced fish oxidized alanine at temperatures close to 0 degrees C and grew over the range 0 degrees C-35 degrees C. The rate of oxidation of alanine, measured manometrically, by cells grown at 2 degrees C was lower than that of cells grown at 22 degrees C. However, the consumption of oxygen after heat treatment at 35 degrees for 35 min was reduced considerably by 2 degrees C grown cells. Alanine oxidase activity was tested in an extract from cells grown at 2 degrees C and 22 degrees C with alanine as the sole carbon, nitrogen, and energy source. Cells grown at 2 degrees C produced an alanine oxidase with a temperature optimum of 35 degrees C and pH optimum of 8, which lost about 80% activity by heat treatment at 40 degrees C for 30 min. There was no change in activity after dialysis at pH 7, 8, or 9. Extracts from cells grown at 22 degrees C contained an alanine oxidase system with an optimum temperature of 45 degrees C, a pH optimum above 8, and only about 30% reduction of activity after heat treatment. This enzyme activity was concentrated in the 0.5 M elution fraction from a Sephadex column, and dialysis reduced the activity at pH 7 and 8. Mesophilic enzyme synthesis apparently started around a growth temperature of 10 degrees C. The crude alanine oxidase systems of Pseudomonas aeruginosa derived from cells grown at 13 degrees C and 37 degrees C had a common optimum temperature of 45 degrees C. These data suggest that one mechanism of psychrophilic growth by psychrotrophic bacteria may be the induction of enzymes with low optimum temperatures in response to low temperature conditions.", "contents": "Temperature-induced alanine oxidation in a psychrotrophic Pseudomonas. A psychrotrophic pseudomonad isolated from iced fish oxidized alanine at temperatures close to 0 degrees C and grew over the range 0 degrees C-35 degrees C. The rate of oxidation of alanine, measured manometrically, by cells grown at 2 degrees C was lower than that of cells grown at 22 degrees C. However, the consumption of oxygen after heat treatment at 35 degrees for 35 min was reduced considerably by 2 degrees C grown cells. Alanine oxidase activity was tested in an extract from cells grown at 2 degrees C and 22 degrees C with alanine as the sole carbon, nitrogen, and energy source. Cells grown at 2 degrees C produced an alanine oxidase with a temperature optimum of 35 degrees C and pH optimum of 8, which lost about 80% activity by heat treatment at 40 degrees C for 30 min. There was no change in activity after dialysis at pH 7, 8, or 9. Extracts from cells grown at 22 degrees C contained an alanine oxidase system with an optimum temperature of 45 degrees C, a pH optimum above 8, and only about 30% reduction of activity after heat treatment. This enzyme activity was concentrated in the 0.5 M elution fraction from a Sephadex column, and dialysis reduced the activity at pH 7 and 8. Mesophilic enzyme synthesis apparently started around a growth temperature of 10 degrees C. The crude alanine oxidase systems of Pseudomonas aeruginosa derived from cells grown at 13 degrees C and 37 degrees C had a common optimum temperature of 45 degrees C. These data suggest that one mechanism of psychrophilic growth by psychrotrophic bacteria may be the induction of enzymes with low optimum temperatures in response to low temperature conditions."}
{"id": "PMID:3274", "title": "Growth characteristics of a cell line derived from the pig oviduct.", "content": "Further evidence for the establishment of the pig fallopian tube (PFT) cell line as a continuous cell line was shown by an increase in the maximum population density as the number of subcultures increased. The optimal pH and temperature-growth ranges appeared to be 7.4-7.8 and 37-41 degrees C respectively, and the population doubling time was 20-25 h under optimal growth conditions. With progressive subculture, the serum requirements dropped from 20 to 2%. A plating efficiency of 2 to 4% was found in all serial subcultures. Colonies were observed in agar suspension culture at the 146th subculture and thereafter. Chromosomal alterations were found in the 100th subculture and thereafter.", "contents": "Growth characteristics of a cell line derived from the pig oviduct. Further evidence for the establishment of the pig fallopian tube (PFT) cell line as a continuous cell line was shown by an increase in the maximum population density as the number of subcultures increased. The optimal pH and temperature-growth ranges appeared to be 7.4-7.8 and 37-41 degrees C respectively, and the population doubling time was 20-25 h under optimal growth conditions. With progressive subculture, the serum requirements dropped from 20 to 2%. A plating efficiency of 2 to 4% was found in all serial subcultures. Colonies were observed in agar suspension culture at the 146th subculture and thereafter. Chromosomal alterations were found in the 100th subculture and thereafter."}
{"id": "PMID:3275", "title": "Characteristics of a facultatively psychrophilic Acinetobacter species isolated from river sediment.", "content": "A facultatively psychrophilic bacterium isolated from river sediment was identified as an Acinetobacter species, similar to those previously characterized as A. lwoffi. The strain was extremely lipolytic and hemolytic. Some action on crude oil was also observed. The organism was able to utilize a wide variety of carbon and energy sources when tested at both 20 and 30 degrees C. A comparison is made with the previously proposed type strain of A. lwoffi. The bacteria had a Gram-negative cell wall containing an electron-dense intermediate layer. Cell division occurred with the formation of a septum and slight constriction.", "contents": "Characteristics of a facultatively psychrophilic Acinetobacter species isolated from river sediment. A facultatively psychrophilic bacterium isolated from river sediment was identified as an Acinetobacter species, similar to those previously characterized as A. lwoffi. The strain was extremely lipolytic and hemolytic. Some action on crude oil was also observed. The organism was able to utilize a wide variety of carbon and energy sources when tested at both 20 and 30 degrees C. A comparison is made with the previously proposed type strain of A. lwoffi. The bacteria had a Gram-negative cell wall containing an electron-dense intermediate layer. Cell division occurred with the formation of a septum and slight constriction."}
{"id": "PMID:3276", "title": "Zoospore chemotaxis in Australian isolates of Phytophthora species.", "content": "Zoospores of Australian isolates of Phytophthora drechsleri, P. cryptogea, P. cinnamomi, P. nicotianae var. parasitica, and P. citricola were examined for their chemotactic responses to asparagine, glutamine, aspartate, glutamate, and structurally related compounds. Structural requirements for attraction include the alpha-amino-acid group with a short carbon chain terminating in an amide group. The one American isolate tested gave a different result and possible reasons for this are discussed. The pH of the environment was important, a neutral-charged molecule was more attractive than a negatively charged molecule, hence glutamine and aspartate were more attractive at pH 3.0 than pH 5.0. Zoospores tended to move away from regions with a high hydrogen ion concentration. Compounds other than amino acids were slightly attractive including several sugars and ethanol. Synergistic interactions between amino acids, ethanol, and sucrose were observed and may account for the high levels of attraction of zoospores to root exudates and extracts.", "contents": "Zoospore chemotaxis in Australian isolates of Phytophthora species. Zoospores of Australian isolates of Phytophthora drechsleri, P. cryptogea, P. cinnamomi, P. nicotianae var. parasitica, and P. citricola were examined for their chemotactic responses to asparagine, glutamine, aspartate, glutamate, and structurally related compounds. Structural requirements for attraction include the alpha-amino-acid group with a short carbon chain terminating in an amide group. The one American isolate tested gave a different result and possible reasons for this are discussed. The pH of the environment was important, a neutral-charged molecule was more attractive than a negatively charged molecule, hence glutamine and aspartate were more attractive at pH 3.0 than pH 5.0. Zoospores tended to move away from regions with a high hydrogen ion concentration. Compounds other than amino acids were slightly attractive including several sugars and ethanol. Synergistic interactions between amino acids, ethanol, and sucrose were observed and may account for the high levels of attraction of zoospores to root exudates and extracts."}
{"id": "PMID:3279", "title": "Double-blind evaluation of oral L-prolyl-Lleucyl-glycine amide in Parkinson's disease.", "content": "A 4-month double-blind study comparing the effect of increasing oral doses (up to 1.0 g daily) of synthetic L-proyl-L-leucyl-glycine amide (PLG) and placebo in 20 parkinsonian patients showed no significant improvement in objective scores of functional disability. However, important trends and some significant results were observed with the lower doses of PLG. These essentially negative results may be attributed to poor intestinal absorption of the compound, a short biologic half-life in the blood, or administration of oral doses that were much higher than required, or a combination of factors. In further studies with this peptide, which are encouraged, the intravenous route should be used until the question of intestinal absorption is resolved.", "contents": "Double-blind evaluation of oral L-prolyl-Lleucyl-glycine amide in Parkinson's disease. A 4-month double-blind study comparing the effect of increasing oral doses (up to 1.0 g daily) of synthetic L-proyl-L-leucyl-glycine amide (PLG) and placebo in 20 parkinsonian patients showed no significant improvement in objective scores of functional disability. However, important trends and some significant results were observed with the lower doses of PLG. These essentially negative results may be attributed to poor intestinal absorption of the compound, a short biologic half-life in the blood, or administration of oral doses that were much higher than required, or a combination of factors. In further studies with this peptide, which are encouraged, the intravenous route should be used until the question of intestinal absorption is resolved."}
{"id": "PMID:3280", "title": "Carcinoid tumors of the thymus.", "content": "Three patients with carcinoid tumors of the anterior mediastinum are described. Study of these patients and an analysis of previously reported cases indicates that the thymus is the primary site of these tumors, which are probably related to the presence of Kulchitsky cells in normal thymus. These neoplasms differ clinically and anatomically from conventional thymomas. They occur predominantly in men, are not associated with myasthenia gravis or red-cell hypoplasia, and are more aggressive tumors than thymomas. Histologically, they are similar to carcinoid tumors of other organs and differ from the variable combination of epithelial cells and lymphocytes of thymomas. Although they are usually locally invasive and frequently metastasize, the clinical course is usually protracted. It is probable that the reported examples of Cushing's syndrome related to thymomas were actually associated with thymic carcinoid tumors.", "contents": "Carcinoid tumors of the thymus. Three patients with carcinoid tumors of the anterior mediastinum are described. Study of these patients and an analysis of previously reported cases indicates that the thymus is the primary site of these tumors, which are probably related to the presence of Kulchitsky cells in normal thymus. These neoplasms differ clinically and anatomically from conventional thymomas. They occur predominantly in men, are not associated with myasthenia gravis or red-cell hypoplasia, and are more aggressive tumors than thymomas. Histologically, they are similar to carcinoid tumors of other organs and differ from the variable combination of epithelial cells and lymphocytes of thymomas. Although they are usually locally invasive and frequently metastasize, the clinical course is usually protracted. It is probable that the reported examples of Cushing's syndrome related to thymomas were actually associated with thymic carcinoid tumors."}
{"id": "PMID:3281", "title": "Effects of hypoxia on distribution of cardiac output and organ blood flow in the rabbit. Regional vascular response to hypoxia.", "content": "The hemodynamic responses of various vascular beds in the systemic circulation to prolonged moderate hypoxia were studied in the rabbit using the radioactive microsphere method. Although cardiac output remained unchanged, there was a redistribution of blood flow in which blood was mainly diverted from the kidneys to provide greater supply to heart, brain and skeletal muscle. These regional adjustments are similar to those seen after low cardiac output due to hemorrhage or endotoxic shock.", "contents": "Effects of hypoxia on distribution of cardiac output and organ blood flow in the rabbit. Regional vascular response to hypoxia. The hemodynamic responses of various vascular beds in the systemic circulation to prolonged moderate hypoxia were studied in the rabbit using the radioactive microsphere method. Although cardiac output remained unchanged, there was a redistribution of blood flow in which blood was mainly diverted from the kidneys to provide greater supply to heart, brain and skeletal muscle. These regional adjustments are similar to those seen after low cardiac output due to hemorrhage or endotoxic shock."}
{"id": "PMID:3284", "title": "Quenching of tryptophanyl fluorescence of human growth hormone by iodide.", "content": "Quenching of tryptophanyl fluorescence of human growth hormone by I- followed saturation kinetics and was abolished by KSCN. In the presence of 6 M guanidine hydrochloride quenching was linear between 0 to 0.2 M KI. These results suggest that I- quenched the fluorescence of the native hormone by binding at or near the single tryptophanyl residue. Quenching by 0.1 M KI decreased exponentially with increasing concentrations of human and bovine growth hormones. Acidification did not have a significant effect on quenching of the human hormone, but it markedly decreased quenching of the bovine hormone. Conformational differences at the vicinity of the lone tryptophanyl residue that could be inferred by these and other experiments may be contributing to the biological specificity of native human and bovine growth hormones.", "contents": "Quenching of tryptophanyl fluorescence of human growth hormone by iodide. Quenching of tryptophanyl fluorescence of human growth hormone by I- followed saturation kinetics and was abolished by KSCN. In the presence of 6 M guanidine hydrochloride quenching was linear between 0 to 0.2 M KI. These results suggest that I- quenched the fluorescence of the native hormone by binding at or near the single tryptophanyl residue. Quenching by 0.1 M KI decreased exponentially with increasing concentrations of human and bovine growth hormones. Acidification did not have a significant effect on quenching of the human hormone, but it markedly decreased quenching of the bovine hormone. Conformational differences at the vicinity of the lone tryptophanyl residue that could be inferred by these and other experiments may be contributing to the biological specificity of native human and bovine growth hormones."}
{"id": "PMID:3285", "title": "Comparison of the metabolism of benzo[alpha]pyrene and binding to DNA caused by rat liver nuclei and microsomes.", "content": "Administration of 3-methylcholanthrene (3MC) to rats greatly enhanced the aryl hydrocarbon hydroxylase (AHH) activity of liver nuclei. However, the binding in vitro [3H]benzo[alpha]pyrene (BP) to DNA within the nuclei which occurred at the same time as hydroxylation of BP was much less enhanced. Thin layer chromatography of the metabolites of BP produced by these nuclei revealed the same metabolites in similar relative amounts as were produced by rat liver microsomes prepared from rats which had received 3MC. The binding to DNA was further analysed by hydrolysis of the DNA and fractionation on a Sephadex column. This analysis revealed that the binding to DAN in nuclei was very similar in nature to that which occurred when calf-thymus DNA was added to microsomes metabolising BP.", "contents": "Comparison of the metabolism of benzo[alpha]pyrene and binding to DNA caused by rat liver nuclei and microsomes. Administration of 3-methylcholanthrene (3MC) to rats greatly enhanced the aryl hydrocarbon hydroxylase (AHH) activity of liver nuclei. However, the binding in vitro [3H]benzo[alpha]pyrene (BP) to DNA within the nuclei which occurred at the same time as hydroxylation of BP was much less enhanced. Thin layer chromatography of the metabolites of BP produced by these nuclei revealed the same metabolites in similar relative amounts as were produced by rat liver microsomes prepared from rats which had received 3MC. The binding to DNA was further analysed by hydrolysis of the DNA and fractionation on a Sephadex column. This analysis revealed that the binding to DAN in nuclei was very similar in nature to that which occurred when calf-thymus DNA was added to microsomes metabolising BP."}
{"id": "PMID:3286", "title": "Inhibition of nadph-driven microsomal lipid peroxidation by cytosol factor(s). Effect of a fat-free, high carbohydrate diet.", "content": "Male Swiss mice were given free access to a fat-free, high carbohydrate diet. The liver cytosol fraction from these mice contained a heat-sensitive factor that markedly inhibited microsomal, ferric pyrophosphate stimulated, NADPH-driven lipid peroxidation. The diet-induced factor was apparently incorporated into the microsomes after 12 days of continuous feeding, since lipid peroxidation by these microsomes was strongly diminished. The factor disappeared from the cytosol after 24 h of fasting and reappeared after refeeding the mice with the fat-free, high carbohydrate diet.", "contents": "Inhibition of nadph-driven microsomal lipid peroxidation by cytosol factor(s). Effect of a fat-free, high carbohydrate diet. Male Swiss mice were given free access to a fat-free, high carbohydrate diet. The liver cytosol fraction from these mice contained a heat-sensitive factor that markedly inhibited microsomal, ferric pyrophosphate stimulated, NADPH-driven lipid peroxidation. The diet-induced factor was apparently incorporated into the microsomes after 12 days of continuous feeding, since lipid peroxidation by these microsomes was strongly diminished. The factor disappeared from the cytosol after 24 h of fasting and reappeared after refeeding the mice with the fat-free, high carbohydrate diet."}
{"id": "PMID:3287", "title": "The repression and derepression of hepatic tyrosine aminotransferase by carcinogens.", "content": "Like hydrocortisone, a single carcinogenic dose of dimethylnitrosamine (50 mg/kg) initiates the induction cycle for hepatic tyrosine aminotransferase in adrenalectomized rats. However, following this initial induction in the presence of dimethylnitrosamine, the enzyme becomes refractory to reinduction by known inducers. The administration of thioacetamide to either adrenalectomized or intact rats leads to an immediate and progressive loss of inducibility by hydrocortisone, dibutyrylcyclic AMP or dimethylnitrosamine. Although the thioacetamide-induced repression was not reversed even up to 10 weekds after the cessation of treatment, it was reversed after the induction of liver regeneration. Both the carcinogen-mediated induction and repression of tyrosine aminotransferase appears to occur by mechanisms which do not involve the corticosteroid-binding proteins which normally mediate the induction by glucocorticoids.", "contents": "The repression and derepression of hepatic tyrosine aminotransferase by carcinogens. Like hydrocortisone, a single carcinogenic dose of dimethylnitrosamine (50 mg/kg) initiates the induction cycle for hepatic tyrosine aminotransferase in adrenalectomized rats. However, following this initial induction in the presence of dimethylnitrosamine, the enzyme becomes refractory to reinduction by known inducers. The administration of thioacetamide to either adrenalectomized or intact rats leads to an immediate and progressive loss of inducibility by hydrocortisone, dibutyrylcyclic AMP or dimethylnitrosamine. Although the thioacetamide-induced repression was not reversed even up to 10 weekds after the cessation of treatment, it was reversed after the induction of liver regeneration. Both the carcinogen-mediated induction and repression of tyrosine aminotransferase appears to occur by mechanisms which do not involve the corticosteroid-binding proteins which normally mediate the induction by glucocorticoids."}
{"id": "PMID:3291", "title": "[Effect of intratumoral injection of bacterial and viral neuraminidase in rats].", "content": "We studied the effect of neuraminidase injection in rat's tumor at different doses: 5,10,50,100, 500 U and we concluded that: There was no difference between the rats treated with 5,10,50 U and the controls. The y died 3 weeks after the injection. But the rats treated by 100 at 500 U of NA died quickley, in the week, of long metastases.", "contents": "[Effect of intratumoral injection of bacterial and viral neuraminidase in rats]. We studied the effect of neuraminidase injection in rat's tumor at different doses: 5,10,50,100, 500 U and we concluded that: There was no difference between the rats treated with 5,10,50 U and the controls. The y died 3 weeks after the injection. But the rats treated by 100 at 500 U of NA died quickley, in the week, of long metastases."}
{"id": "PMID:3292", "title": "[Changes in transmitter release at frog neuromuscular junction induced by 4-aminopyridine].", "content": "4-aminopyridine (4-AP) at micromolar concentrations, increases the end-plate potential amplitude in curarized preparations and the mean quantal content in every preparation tested, but the spontaneous release is not modified by 4-AP. These results can explain the anticurare activity observed in the wole animal or in vitro. 4-AP prolongs the falling phase of the muscle action potential without change in the muscle membrane potential.", "contents": "[Changes in transmitter release at frog neuromuscular junction induced by 4-aminopyridine]. 4-aminopyridine (4-AP) at micromolar concentrations, increases the end-plate potential amplitude in curarized preparations and the mean quantal content in every preparation tested, but the spontaneous release is not modified by 4-AP. These results can explain the anticurare activity observed in the wole animal or in vitro. 4-AP prolongs the falling phase of the muscle action potential without change in the muscle membrane potential."}
{"id": "PMID:3293", "title": "Contribution of tissue acidosis to ischemic injury in the perfused rat heart.", "content": "The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.", "contents": "Contribution of tissue acidosis to ischemic injury in the perfused rat heart. The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed."}
{"id": "PMID:3294", "title": "Polarographic method for rapid microdetermination of cholesterol with cholesterol esterase and cholesterol oxidase.", "content": "Cholesterol concentrations in serum are enzymatically determined rapidly by use of a polarographic oxygen analyzer with a circuit modified to record simultaneously the amount and rate of oxygen consumption. The final assay system, assessed from the oxygen consumption value that we found to be optimum, consists of 1 ml of sodium phosphate buffer (0.6 mol/liter, pH 7.0) containing NaN3 (10 mg/liter), Triton X-100 surfactant (10 ml/liter), 0.4 U of cholesterol ester hydrolase, and 0.6 U of cholesterol oxidase. Oxygen consumption and cholesterol concentration are linearly related to 8.0 g/liter, and only 10 mul of serum is required. Replicate analyses of pooled serum by the present method demonstrated the following inter-run precision: mean = 1731 mg/liter, SD = 22.3 mg/liter, CV = 1.3%. Bilirubin and ascorbic acid were without effect on the present method, unlike the enzymatic colorimetric methods.", "contents": "Polarographic method for rapid microdetermination of cholesterol with cholesterol esterase and cholesterol oxidase. Cholesterol concentrations in serum are enzymatically determined rapidly by use of a polarographic oxygen analyzer with a circuit modified to record simultaneously the amount and rate of oxygen consumption. The final assay system, assessed from the oxygen consumption value that we found to be optimum, consists of 1 ml of sodium phosphate buffer (0.6 mol/liter, pH 7.0) containing NaN3 (10 mg/liter), Triton X-100 surfactant (10 ml/liter), 0.4 U of cholesterol ester hydrolase, and 0.6 U of cholesterol oxidase. Oxygen consumption and cholesterol concentration are linearly related to 8.0 g/liter, and only 10 mul of serum is required. Replicate analyses of pooled serum by the present method demonstrated the following inter-run precision: mean = 1731 mg/liter, SD = 22.3 mg/liter, CV = 1.3%. Bilirubin and ascorbic acid were without effect on the present method, unlike the enzymatic colorimetric methods."}
{"id": "PMID:3295", "title": "Measurement of 25-hydroxyvitamin D3 in serum.", "content": "We describe a method for measuring 25-hydroxyvitamin D3 in serum. Extraction with dichloromethane/methanol (2/1 by vol), followed by chromatography on a column of Sephadex LH-20, resulted in an overall analytical recovery of 82% +/- 3.5% (SD). Diluted normal rat serum was used as binding protein because it contains a transport protein that has both a high affinity (Ka = 2 X 10(10) liter/mol) and a high capacity (3 X 10(-6) mol/liter) for 25-hydroxyvitamin D3. There is no advantage in using more complex binding proteins derived either from rachitic animals or from cytosol preparations. Concentrations of 25-hydroxyvitamin D3 (13.4 +/- 4 mug/liter) in the serum of apparently normal Belgian subjects are lower than those reported for North Americans, but resemble those reported for the United Kingdom.", "contents": "Measurement of 25-hydroxyvitamin D3 in serum. We describe a method for measuring 25-hydroxyvitamin D3 in serum. Extraction with dichloromethane/methanol (2/1 by vol), followed by chromatography on a column of Sephadex LH-20, resulted in an overall analytical recovery of 82% +/- 3.5% (SD). Diluted normal rat serum was used as binding protein because it contains a transport protein that has both a high affinity (Ka = 2 X 10(10) liter/mol) and a high capacity (3 X 10(-6) mol/liter) for 25-hydroxyvitamin D3. There is no advantage in using more complex binding proteins derived either from rachitic animals or from cytosol preparations. Concentrations of 25-hydroxyvitamin D3 (13.4 +/- 4 mug/liter) in the serum of apparently normal Belgian subjects are lower than those reported for North Americans, but resemble those reported for the United Kingdom."}
{"id": "PMID:3296", "title": "Gamma-glutamyltransferase: Substrate inhibition, kinetic mechanism, and assay conditions.", "content": "Gamma-glutamyltransferase activity in serum is shown to be competitively inhibited by the two substrates gamma-glutamyl-4-nitroanilide and glycylglycine. Awareness of this is of importance when one is choosing final reaction conditions for the assay of the enzyme. Gamma-glutamyltransferase probably acts by a \"ping-pong bi-bi\" kinetic mechanism, which fits with the double competitive substrate inhibition demonstrated. The product, 4-nitro-aniline, appears to be an uncompetitive dead-end inhibitor of both substrates. Various amino acids, particularly glycine and L-alanine, inhibit the enzyme. Their inhibition patterns are uncompetitive with glycylglycine and competitive with gamma-glutamyl-4-nitroanilide. On the basis of the present and other studies, the Scandinavian Society for Clinical Chemistry and Clinical Physiology is going to recommend for routine use a gamma-glutamyltransferase method in which the final concentrations of gamma-glutamyl-4-nitroanilide and glycylglycine are 4 and 75 mmol/liter, respectively.", "contents": "Gamma-glutamyltransferase: Substrate inhibition, kinetic mechanism, and assay conditions. Gamma-glutamyltransferase activity in serum is shown to be competitively inhibited by the two substrates gamma-glutamyl-4-nitroanilide and glycylglycine. Awareness of this is of importance when one is choosing final reaction conditions for the assay of the enzyme. Gamma-glutamyltransferase probably acts by a \"ping-pong bi-bi\" kinetic mechanism, which fits with the double competitive substrate inhibition demonstrated. The product, 4-nitro-aniline, appears to be an uncompetitive dead-end inhibitor of both substrates. Various amino acids, particularly glycine and L-alanine, inhibit the enzyme. Their inhibition patterns are uncompetitive with glycylglycine and competitive with gamma-glutamyl-4-nitroanilide. On the basis of the present and other studies, the Scandinavian Society for Clinical Chemistry and Clinical Physiology is going to recommend for routine use a gamma-glutamyltransferase method in which the final concentrations of gamma-glutamyl-4-nitroanilide and glycylglycine are 4 and 75 mmol/liter, respectively."}
{"id": "PMID:3297", "title": "New techniques for ion-selective measurements of ionized calcium in serum after pH adjustment of aerobically handled sera.", "content": "I report further experience in measuring ionized calcium (Ca2+) with the AMT Electron System and its serum standards and solid-state, dip, calcium-selective electrodes. With this system, serum pH can be adjusted with CO2 gas and Ca2+ and pH simultaneously measured; when 5.2% CO2 (40 mm pco2) is used for sample equilibration, the standard bicarbonate concentration is also provided. I measured serum Ca2+ as a function of pH between pH 7.0 and 9.0 and found the relationship to be reproducible, with no evidence of irreversible complexing of Ca2+. When the pH of aerobically exposed, mailed sera was restored to the original values, their values for Ca2+ were the same as for the fresh sera. Measurement of Ca2+ in routinely (aerobically) handled sera after pH restoration with CO2 gas was therefore validated, both samples from within an institution and mailed specimens. Standardization to pH 7.40 is recommended for routine measurements, is generally more accurate than use of heparin or quasianaerobic techniques, and is a practical approach. In patients with possible uncompensated acid-base disturbance (which may be indicated by an abnormal standard bicarbonate concentration if not suspected clinically), patient pH should be measured independently as part of the usual strict, anaerobic blood-gas-analysis procedures. Abnormal patient pH must be considered in the interpretation of Ca2+ results determined at pH 7.40 which are borderline or slightly abnormal; most accurately, Ca2+ may be measured in the separated sera at the previously determined patient pH value. Studies of aqueous solutions with the currently used Ca2+ electrodes showed a selectivity coefficient (the constant which relates the activity of an interfering ion to the activity of calcium that would contribute the same emf) KNa=0.0031 +/- 0.0003 (SE) and KMg=0.046 +/- 0.004 (SE). At physiological concentrations of Ca2+, physiologically encountered variation in Na+ is of no significance in resulting Ca2+, but extreme variation in Mg2+ may cause an error of approximately 1%.", "contents": "New techniques for ion-selective measurements of ionized calcium in serum after pH adjustment of aerobically handled sera. I report further experience in measuring ionized calcium (Ca2+) with the AMT Electron System and its serum standards and solid-state, dip, calcium-selective electrodes. With this system, serum pH can be adjusted with CO2 gas and Ca2+ and pH simultaneously measured; when 5.2% CO2 (40 mm pco2) is used for sample equilibration, the standard bicarbonate concentration is also provided. I measured serum Ca2+ as a function of pH between pH 7.0 and 9.0 and found the relationship to be reproducible, with no evidence of irreversible complexing of Ca2+. When the pH of aerobically exposed, mailed sera was restored to the original values, their values for Ca2+ were the same as for the fresh sera. Measurement of Ca2+ in routinely (aerobically) handled sera after pH restoration with CO2 gas was therefore validated, both samples from within an institution and mailed specimens. Standardization to pH 7.40 is recommended for routine measurements, is generally more accurate than use of heparin or quasianaerobic techniques, and is a practical approach. In patients with possible uncompensated acid-base disturbance (which may be indicated by an abnormal standard bicarbonate concentration if not suspected clinically), patient pH should be measured independently as part of the usual strict, anaerobic blood-gas-analysis procedures. Abnormal patient pH must be considered in the interpretation of Ca2+ results determined at pH 7.40 which are borderline or slightly abnormal; most accurately, Ca2+ may be measured in the separated sera at the previously determined patient pH value. Studies of aqueous solutions with the currently used Ca2+ electrodes showed a selectivity coefficient (the constant which relates the activity of an interfering ion to the activity of calcium that would contribute the same emf) KNa=0.0031 +/- 0.0003 (SE) and KMg=0.046 +/- 0.004 (SE). At physiological concentrations of Ca2+, physiologically encountered variation in Na+ is of no significance in resulting Ca2+, but extreme variation in Mg2+ may cause an error of approximately 1%."}
{"id": "PMID:3298", "title": "Effect of tobramycin on urinary gamma-glutamyltransferase activity: Studies in a case of renal carcinoma.", "content": "Gamma-Glutamyltransferase activity was studied in a man presenting with recurrent septicemia owing to pyonephrosis and renal carcinoma. Increased activity in the urine was ascribable to administration of the aminoglycoside antibiotic, tobramycin. That the renal carcinoma did not contribute to the increased values was confirmed by homogenization and enzyme histochemistry of the tumor. Although the activity of this enzyme in serum was greater than normal, this persisted postoperatively, and thus was not related to the renal carcinoma.", "contents": "Effect of tobramycin on urinary gamma-glutamyltransferase activity: Studies in a case of renal carcinoma. Gamma-Glutamyltransferase activity was studied in a man presenting with recurrent septicemia owing to pyonephrosis and renal carcinoma. Increased activity in the urine was ascribable to administration of the aminoglycoside antibiotic, tobramycin. That the renal carcinoma did not contribute to the increased values was confirmed by homogenization and enzyme histochemistry of the tumor. Although the activity of this enzyme in serum was greater than normal, this persisted postoperatively, and thus was not related to the renal carcinoma."}
{"id": "PMID:3301", "title": "Electrophoresis of gamma-glutamyltranspeptidase on cellogel. The appearance of the alpha2-beta band in positive LP-X sera.", "content": "Fractionations of serum gamma-glutamyltranspeptidase (gamma-GT) and determinations of the \"abnormal serum lipoprotein X\" (LP-X) have been carried out in sera from patients with different hepatobiliary disorders. LP-X was used to demonstrate or exclude cholestasis. One gamma-GT fraction, alpha2-beta, may be of interest to distinguish between extrahepatic obstruction and intrahepatic cholestasis as was revealed by statistical analysis.", "contents": "Electrophoresis of gamma-glutamyltranspeptidase on cellogel. The appearance of the alpha2-beta band in positive LP-X sera. Fractionations of serum gamma-glutamyltranspeptidase (gamma-GT) and determinations of the \"abnormal serum lipoprotein X\" (LP-X) have been carried out in sera from patients with different hepatobiliary disorders. LP-X was used to demonstrate or exclude cholestasis. One gamma-GT fraction, alpha2-beta, may be of interest to distinguish between extrahepatic obstruction and intrahepatic cholestasis as was revealed by statistical analysis."}
{"id": "PMID:3304", "title": "Multiple changes in distal stop-flow electrolyte patterns and reduction of acid excretion induced in rabbits by angiotensin.", "content": "1. Angiotensin has previously been shown to inhibit distal renal tubular sodium reabsorption. As a consequence of this, or independently, it might influence the distal handling of other electrolytes. We have therefore examined the effects of angiotensin on the distal reabsorption or secretion of a spectrum of electrolytes. 2. Standard bilateral stop-flow studies were done on anaesthetized, adrenalectomized rabbits, in which the effects of intravenous infusions of either 0-02-0-05 mug min-1 kg-1 or 1 mug min-1 kg-1 of angiotensin were compared with control stop-flow results. 3. The lower dose of angiotensin inhibited distal sodium, chloride, water and magnesium reabsorption, inhibited distal hydrogen secretion and stimulated distal potassium secretion. The higher dose of angiotensin produced these changes and additionally inhibited distal calcium reabsorption. Most of the observed changes were dose-related. The low dose of angiotensin did not significantly raise blood pressure but the high dose was pressor. 4. Changes in the stop-flow patterns induced by the higher dose of angiotensin were compatible with, and may help to explain, the changes it produced in urinary excretion of sodium, chloride, potassium, magnesium and calcium in clearance studies before stop-flow. Suppression of hydrogen secretion caused by both doses of angiotensin in the stop-flow studies was also reflected by reductions in acid excretion produced by these infusion rates in additional experiments performed by clearance methods in acid-loaded, conscious rabbits. 5. The results support the view that angiotensin may have an important intrarenal role, at least in rabbits.", "contents": "Multiple changes in distal stop-flow electrolyte patterns and reduction of acid excretion induced in rabbits by angiotensin. 1. Angiotensin has previously been shown to inhibit distal renal tubular sodium reabsorption. As a consequence of this, or independently, it might influence the distal handling of other electrolytes. We have therefore examined the effects of angiotensin on the distal reabsorption or secretion of a spectrum of electrolytes. 2. Standard bilateral stop-flow studies were done on anaesthetized, adrenalectomized rabbits, in which the effects of intravenous infusions of either 0-02-0-05 mug min-1 kg-1 or 1 mug min-1 kg-1 of angiotensin were compared with control stop-flow results. 3. The lower dose of angiotensin inhibited distal sodium, chloride, water and magnesium reabsorption, inhibited distal hydrogen secretion and stimulated distal potassium secretion. The higher dose of angiotensin produced these changes and additionally inhibited distal calcium reabsorption. Most of the observed changes were dose-related. The low dose of angiotensin did not significantly raise blood pressure but the high dose was pressor. 4. Changes in the stop-flow patterns induced by the higher dose of angiotensin were compatible with, and may help to explain, the changes it produced in urinary excretion of sodium, chloride, potassium, magnesium and calcium in clearance studies before stop-flow. Suppression of hydrogen secretion caused by both doses of angiotensin in the stop-flow studies was also reflected by reductions in acid excretion produced by these infusion rates in additional experiments performed by clearance methods in acid-loaded, conscious rabbits. 5. The results support the view that angiotensin may have an important intrarenal role, at least in rabbits."}
{"id": "PMID:3305", "title": "The acute effects of respiratory and metabolic acidosis on renal function in the dog.", "content": "1. Effective renal plasma flow, glomerular filtration rate and cardiac output were measured in osmotically loaded dogs before and during comparable acute respiratory and metabolic acidosis. 2. Urine output increased in control dogs and in animals with metabolic acidosis, but declined with respiratory acidosis. Effective renal plasma flow and glomerular filtration rate declined with respiratory and metabolic acidosis. 3. When respiratory acidosis was buffered with sodium bicarbonate, urine volume increased and glomerular filtration rate and effective renal plasma flow were unchanged; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate and effective renal plasma flow fell. 4. When metabolic acidosis was buffered with sodium bicarbonate, urine volume increased; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate fell. Cardiac output declined only during metabolic acidosis, both buffered and unbuffered. 5. These studies demonstrate that, even with osmotic loading: (1) respiratory acidosis caused a decrease in glomerular filtration rate, effective renal plasma flow and urine volume; (2) metabolic acidosis depresses glomerular filtration rate and effective renal plasma flow but does not change urine volume even though cardiac output falls; (3) sodium bicarbonate is mor effective than trihydroxymethylaminomethane in preserving renal function during respiratory and metabolic acidosis.", "contents": "The acute effects of respiratory and metabolic acidosis on renal function in the dog. 1. Effective renal plasma flow, glomerular filtration rate and cardiac output were measured in osmotically loaded dogs before and during comparable acute respiratory and metabolic acidosis. 2. Urine output increased in control dogs and in animals with metabolic acidosis, but declined with respiratory acidosis. Effective renal plasma flow and glomerular filtration rate declined with respiratory and metabolic acidosis. 3. When respiratory acidosis was buffered with sodium bicarbonate, urine volume increased and glomerular filtration rate and effective renal plasma flow were unchanged; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate and effective renal plasma flow fell. 4. When metabolic acidosis was buffered with sodium bicarbonate, urine volume increased; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate fell. Cardiac output declined only during metabolic acidosis, both buffered and unbuffered. 5. These studies demonstrate that, even with osmotic loading: (1) respiratory acidosis caused a decrease in glomerular filtration rate, effective renal plasma flow and urine volume; (2) metabolic acidosis depresses glomerular filtration rate and effective renal plasma flow but does not change urine volume even though cardiac output falls; (3) sodium bicarbonate is mor effective than trihydroxymethylaminomethane in preserving renal function during respiratory and metabolic acidosis."}
{"id": "PMID:3306", "title": "The haemodynamic effects of metabolic acidosis in the rat.", "content": "1. The effect of metabolic acidosis of 4-6 h duration on cardiac output, blood pressure, heart rate, and hepatic and renal blood flow has been studied in the rat. 2. In anaesthetized rats, blood pressure and heart rate fell linearly with blood pH in both sham-operated and nephrectomized rats. There was no significant difference between the two groups in the effect of acidosis on either variable. 3. Cardiac output showed a significant fall with increasing acidosis in the conscious rat. 4. Estimated hepatic blood flow in conscious rats showed a significant positive correlation with blood pH in both sham-operated and nephrectomized animals. There was no significant difference in estimated hepatic blood flow between the two groups of animals at any blood pH. 5. In conscious rats, increasing acidosis caused a progressive decrease in estimated renal blood flow. 6. It is concluded that the increase in the previously described apparent renal contribution to lactate removal in the acidotic rat cannot be explained by any circulatory effect mediated by the kidney. The possible relevance of the findings to lactate homeostasis is discussed.", "contents": "The haemodynamic effects of metabolic acidosis in the rat. 1. The effect of metabolic acidosis of 4-6 h duration on cardiac output, blood pressure, heart rate, and hepatic and renal blood flow has been studied in the rat. 2. In anaesthetized rats, blood pressure and heart rate fell linearly with blood pH in both sham-operated and nephrectomized rats. There was no significant difference between the two groups in the effect of acidosis on either variable. 3. Cardiac output showed a significant fall with increasing acidosis in the conscious rat. 4. Estimated hepatic blood flow in conscious rats showed a significant positive correlation with blood pH in both sham-operated and nephrectomized animals. There was no significant difference in estimated hepatic blood flow between the two groups of animals at any blood pH. 5. In conscious rats, increasing acidosis caused a progressive decrease in estimated renal blood flow. 6. It is concluded that the increase in the previously described apparent renal contribution to lactate removal in the acidotic rat cannot be explained by any circulatory effect mediated by the kidney. The possible relevance of the findings to lactate homeostasis is discussed."}
{"id": "PMID:3307", "title": "The effect of acidosis on lactate removal by the perfused rat kidney.", "content": "1. The isolated perfused kidneys of fed rats in normal acid-base status showed a constant rate of lactate removal from the perfusate between 5 and 90 min of perfusion at a perfusate pH of 7-4-7-5. 2. Lactate removal by kidneys of rats in normal acid-base status was stimulated within 30 min by a reduction in perfusate pH to 7-1-7-2, but depressed when perfusate pH was reduced further. 3. Kidneys taken from rats previously made acidotic and perfused with media of various pH values showed a progressive fall in the rate of lactate removal during the perfusion. 4. Glucose output by the kidneys of rats in normal acid-base status perfused with lactate as substrate was not affected by an alteration in perfusate pH. The kidneys of acidotic rats generally showed an increased rate of glucose output compared with those of control rats.", "contents": "The effect of acidosis on lactate removal by the perfused rat kidney. 1. The isolated perfused kidneys of fed rats in normal acid-base status showed a constant rate of lactate removal from the perfusate between 5 and 90 min of perfusion at a perfusate pH of 7-4-7-5. 2. Lactate removal by kidneys of rats in normal acid-base status was stimulated within 30 min by a reduction in perfusate pH to 7-1-7-2, but depressed when perfusate pH was reduced further. 3. Kidneys taken from rats previously made acidotic and perfused with media of various pH values showed a progressive fall in the rate of lactate removal during the perfusion. 4. Glucose output by the kidneys of rats in normal acid-base status perfused with lactate as substrate was not affected by an alteration in perfusate pH. The kidneys of acidotic rats generally showed an increased rate of glucose output compared with those of control rats."}
{"id": "PMID:3386", "title": "Elastin--proteoglycan interaction. Conformational changes of alpha-elastin induced by the interaction.", "content": "The interaction between alpha-elastin and a connective tissue proteoglycan was followed by optical density measurements and circular dichroism spectroscopy. It was found that interaction takes place at pH values below the isoelectric point of elastin with the formation of a complex coacervate. CD spectra demonstrated conformational changes of alpha-elastin caused by the interaction and resulting in an increase in the content of helical structure. This finding suggests the possibility of the involvement of proteoglycans in the molecular organization of elastin.", "contents": "Elastin--proteoglycan interaction. Conformational changes of alpha-elastin induced by the interaction. The interaction between alpha-elastin and a connective tissue proteoglycan was followed by optical density measurements and circular dichroism spectroscopy. It was found that interaction takes place at pH values below the isoelectric point of elastin with the formation of a complex coacervate. CD spectra demonstrated conformational changes of alpha-elastin caused by the interaction and resulting in an increase in the content of helical structure. This finding suggests the possibility of the involvement of proteoglycans in the molecular organization of elastin."}
{"id": "PMID:3387", "title": "Bilateral cryptorchidism in a bull.", "content": "Clinical and pathological observations were made on a case of bilateral cryptorchidism in a bull. Sexual libido could not be assessed because the bull was housed alone. The location of the intraabdominal testes indicated that surgical castration would necessitate a flank laparotomy incision.", "contents": "Bilateral cryptorchidism in a bull. Clinical and pathological observations were made on a case of bilateral cryptorchidism in a bull. Sexual libido could not be assessed because the bull was housed alone. The location of the intraabdominal testes indicated that surgical castration would necessitate a flank laparotomy incision."}
{"id": "PMID:3393", "title": "Treatment of tardive dyskinesia.", "content": "The pathogenesis of tardive dyskinesia is distinct from and may be functionally opposite to that of parkinsonism. The former is thought to be related to central nervous system dopaminergic hyperactivity, while the latter is known to be related to dopamine deficiency. An effective schema for the treatment of tardive dyskinesia includes avoiding antiparkinsonian medication and prescribing deanol, an acetylcholine precursor, while continuing or increasing phenothiazine dosages.", "contents": "Treatment of tardive dyskinesia. The pathogenesis of tardive dyskinesia is distinct from and may be functionally opposite to that of parkinsonism. The former is thought to be related to central nervous system dopaminergic hyperactivity, while the latter is known to be related to dopamine deficiency. An effective schema for the treatment of tardive dyskinesia includes avoiding antiparkinsonian medication and prescribing deanol, an acetylcholine precursor, while continuing or increasing phenothiazine dosages."}
{"id": "PMID:3394", "title": "Epidemiology of tardive dyskinesia Part I.", "content": "We have performed an epidemiological study concerning tardive dyskinesia on a sample of 332 chronic schizophrenic patients (142 males and 190 females, mean age 48.6 years, mean duration of neuroleptic treatment 14.5 years). We could conclude that the age of patients at the time of assessment procedures is the most important variable. The prevalence of tardive dyskinesia was significantly higher in the older population. The significance of an insidious beginning of the illness might be only secondary to the highly significant role of the age. Other factors, such as sex, type of schizophrenia, initial syndrome, present psychic state, organic syndromes and neuroleptic-induced extrapyramidal syndrome, do not seen to play a role in the prevalence of tardive dyskinesia.", "contents": "Epidemiology of tardive dyskinesia Part I. We have performed an epidemiological study concerning tardive dyskinesia on a sample of 332 chronic schizophrenic patients (142 males and 190 females, mean age 48.6 years, mean duration of neuroleptic treatment 14.5 years). We could conclude that the age of patients at the time of assessment procedures is the most important variable. The prevalence of tardive dyskinesia was significantly higher in the older population. The significance of an insidious beginning of the illness might be only secondary to the highly significant role of the age. Other factors, such as sex, type of schizophrenia, initial syndrome, present psychic state, organic syndromes and neuroleptic-induced extrapyramidal syndrome, do not seen to play a role in the prevalence of tardive dyskinesia."}
{"id": "PMID:3392", "title": "Postnatal development of the circadian rhythm of rat liver tyrosine aminotransferase activity.", "content": "The rhythm of tyrosine aminotransferase (TAT) activity in 2-day old rats is characterized by a maximum at the beginning and a further one at the end of light-time. In 7-day old animals, the rhythm is much less pronounced than in 2-day old pups. At the 21st day of life, the rats already exhibit the rhythmic pattern of the adults, although the absolute values are still somewhat below those of the adults. The TAT rhythm in neonates is obviously generated by periodic variations in cyclic AMP-dependent release of TAT from polysomes.", "contents": "Postnatal development of the circadian rhythm of rat liver tyrosine aminotransferase activity. The rhythm of tyrosine aminotransferase (TAT) activity in 2-day old rats is characterized by a maximum at the beginning and a further one at the end of light-time. In 7-day old animals, the rhythm is much less pronounced than in 2-day old pups. At the 21st day of life, the rats already exhibit the rhythmic pattern of the adults, although the absolute values are still somewhat below those of the adults. The TAT rhythm in neonates is obviously generated by periodic variations in cyclic AMP-dependent release of TAT from polysomes."}
{"id": "PMID:3395", "title": "The influence of dehydrocholate on hepatic uptake and biliary excretion of 3H-taurocholate and 3H-ouabain.", "content": "The hepatic uptake and biliary excretion of 3H-taurocholate and 3H-ouabain was studied in the rat during saline (control) and dehydrocholate infusions. Dehydrocholate (140 mumol/hr) did not influence the plasma disappearance nor the biliary excretion of taurocholate after a single iv injection (37 mumol/kg). Bile production in the dehydrocholate experiment was increased 2- to 3-fold compared with controls. The biliary transport maximum for exogenously administered taurocholate was determined by constant infusion to be 135.0 +/- 3.0 mumol/hr (22 mumol/min/g of liver). Concomitant infusions of 140 mumol of dehydrocholate per hr did not alter the maximal taurocholate output. The effects of the two bile salts on bile flow were additive. Dehydrocholate (140 mumol/hr) reduced the biliary excretion of 3H-ouabain (0.8 mumol/kg) and elevated the secondary slow component of the plasma disappearance of the cardiac glycoside. The hepatic levels of ouabain were increased compared with controls. It is concluded that dehydrocholate interferes with ouabain transport at the canalicular level but not with primary hepatic uptake. Taurocholate (140 mumol/hr) failed to influence the total biliary output of ouabain. These differences and the lack of interaction between dehydrocholate and taurocholate suggest a hepatic transporting pathway for taurocholate which differs from that for taurocholate which differs from that for dehydrocholate and/or its metabolites.", "contents": "The influence of dehydrocholate on hepatic uptake and biliary excretion of 3H-taurocholate and 3H-ouabain. The hepatic uptake and biliary excretion of 3H-taurocholate and 3H-ouabain was studied in the rat during saline (control) and dehydrocholate infusions. Dehydrocholate (140 mumol/hr) did not influence the plasma disappearance nor the biliary excretion of taurocholate after a single iv injection (37 mumol/kg). Bile production in the dehydrocholate experiment was increased 2- to 3-fold compared with controls. The biliary transport maximum for exogenously administered taurocholate was determined by constant infusion to be 135.0 +/- 3.0 mumol/hr (22 mumol/min/g of liver). Concomitant infusions of 140 mumol of dehydrocholate per hr did not alter the maximal taurocholate output. The effects of the two bile salts on bile flow were additive. Dehydrocholate (140 mumol/hr) reduced the biliary excretion of 3H-ouabain (0.8 mumol/kg) and elevated the secondary slow component of the plasma disappearance of the cardiac glycoside. The hepatic levels of ouabain were increased compared with controls. It is concluded that dehydrocholate interferes with ouabain transport at the canalicular level but not with primary hepatic uptake. Taurocholate (140 mumol/hr) failed to influence the total biliary output of ouabain. These differences and the lack of interaction between dehydrocholate and taurocholate suggest a hepatic transporting pathway for taurocholate which differs from that for taurocholate which differs from that for dehydrocholate and/or its metabolites."}
{"id": "PMID:3396", "title": "Postnatal development of mixed-function oxidation as measured in microsomes from the small intestine and liver of rabbits.", "content": "The postnatal development of aminopyrine N-demethylase, aniline 4-hydroxylase, benzpyrene hydroxylase, biphenyl 4-hydroxylase, 7-ethoxycoumarin 0-deethylase activities, NADPH-cytochrome c reductase, and cytochrome P-450 was compared in microsomes from the liver and small intestine of New Zealand white rabbits. Apart from hepatic aniline hydroxylase activity, all of the xenobiotic-metabolizing enzyme activities examined had a similar pattern of development in the liver and small intestine. In both tissues the ability to metabolize xenobiotics was generally undetectable at 2 days of age and remained relatively low for the first 20 days of life. Theresfter, a rapid 2- to 5-fold increase in all the enzyme activity studied was noted, and adult values were reached or exceeded by 30 days of age. Subsequent development of xenobiotic-metabolizing enzyme activities in the small intestine, but not in the liver, exhibited a transient fall at 50 days of age before adult activities were attained after 75 days of age. The developmental pattern of cytochrome P-450 in the small intestine closely resembled that of the xenobiotic-metabolizing enzyme activities, but in the liver this correlation was less exact.", "contents": "Postnatal development of mixed-function oxidation as measured in microsomes from the small intestine and liver of rabbits. The postnatal development of aminopyrine N-demethylase, aniline 4-hydroxylase, benzpyrene hydroxylase, biphenyl 4-hydroxylase, 7-ethoxycoumarin 0-deethylase activities, NADPH-cytochrome c reductase, and cytochrome P-450 was compared in microsomes from the liver and small intestine of New Zealand white rabbits. Apart from hepatic aniline hydroxylase activity, all of the xenobiotic-metabolizing enzyme activities examined had a similar pattern of development in the liver and small intestine. In both tissues the ability to metabolize xenobiotics was generally undetectable at 2 days of age and remained relatively low for the first 20 days of life. Theresfter, a rapid 2- to 5-fold increase in all the enzyme activity studied was noted, and adult values were reached or exceeded by 30 days of age. Subsequent development of xenobiotic-metabolizing enzyme activities in the small intestine, but not in the liver, exhibited a transient fall at 50 days of age before adult activities were attained after 75 days of age. The developmental pattern of cytochrome P-450 in the small intestine closely resembled that of the xenobiotic-metabolizing enzyme activities, but in the liver this correlation was less exact."}
{"id": "PMID:3397", "title": "Characterization of the hepatic microsomal mixed-function oxidase enzyme system in miniature pigs.", "content": "Hepatic microsomal protein, cytochrome P-450, UDP-glucuronyltransferase, ethylmorphine demethylase, aniline hydroxylase, and aryl hydrocarbon hydroxylase levels were measured in the 2-, 4-, 5-, 6-, and 8-month-old Hanford miniature pig. The activities or concentrations of all of the liver parameters measured had apparently reached their adult plateau level by 2 months of age. The use of the miniature pig in toxicology research programs is discussed.", "contents": "Characterization of the hepatic microsomal mixed-function oxidase enzyme system in miniature pigs. Hepatic microsomal protein, cytochrome P-450, UDP-glucuronyltransferase, ethylmorphine demethylase, aniline hydroxylase, and aryl hydrocarbon hydroxylase levels were measured in the 2-, 4-, 5-, 6-, and 8-month-old Hanford miniature pig. The activities or concentrations of all of the liver parameters measured had apparently reached their adult plateau level by 2 months of age. The use of the miniature pig in toxicology research programs is discussed."}
{"id": "PMID:3398", "title": "Monooxygenase-catalyzed aldrin epoxidation and dihydroisodrin hydroxylation in monkey liver needle-biopsy specimens. Assay and properties.", "content": "Aldrin epoxidation and dihydroisodrin (1,8,9,10,11,11-hexachloro-2,3-7,6-endo-2,1-7,8-endo-tetracyclo [6.2.1.1(3), (6).0(2), (7)]dodec-9-ene (DHI) hydroxylation have been studied in 0.2-ml liver monooxygenase preparations. Liver biopsy specimens of rhesus (Macaca mulatta) and bonnet (M. radiata) monkeys obtained with a 1.9-mm Menghini needle were the primary enzyme sources. Dieldrin and monohydroxydihydroisodrin (DHI-OH) were the only metabolites detected by electron-capture GLC analysis of hexane extracts of incubation media. Incubation, extraction, and analysis could be done in the same vessel. Maximum rates were obtained in the presence of NADPH and O2, and both transformations were inhibited by CO. The apparent KM and Vmax (+/-SD) for epoxidation was 1.2 +/- 0.2 X 10(-5) M aldrin and 210 +/- 20 pmol of dieldrin per mg of protein per min, and the corresponding values for hydroxylation were 2.3 +/- 0.4 X 10(-5) M DHI and 150 +/- 20 pmol of DHI-OH per mg of protein per min. Aldrin epoxidation and DHI hydroxylation activities of rhesus monkey liver biopsy and rat liver preparations were evaluated after phenobarbital treatment. The assay procedures can be used in protocols in which animals serve as their own controls.", "contents": "Monooxygenase-catalyzed aldrin epoxidation and dihydroisodrin hydroxylation in monkey liver needle-biopsy specimens. Assay and properties. Aldrin epoxidation and dihydroisodrin (1,8,9,10,11,11-hexachloro-2,3-7,6-endo-2,1-7,8-endo-tetracyclo [6.2.1.1(3), (6).0(2), (7)]dodec-9-ene (DHI) hydroxylation have been studied in 0.2-ml liver monooxygenase preparations. Liver biopsy specimens of rhesus (Macaca mulatta) and bonnet (M. radiata) monkeys obtained with a 1.9-mm Menghini needle were the primary enzyme sources. Dieldrin and monohydroxydihydroisodrin (DHI-OH) were the only metabolites detected by electron-capture GLC analysis of hexane extracts of incubation media. Incubation, extraction, and analysis could be done in the same vessel. Maximum rates were obtained in the presence of NADPH and O2, and both transformations were inhibited by CO. The apparent KM and Vmax (+/-SD) for epoxidation was 1.2 +/- 0.2 X 10(-5) M aldrin and 210 +/- 20 pmol of dieldrin per mg of protein per min, and the corresponding values for hydroxylation were 2.3 +/- 0.4 X 10(-5) M DHI and 150 +/- 20 pmol of DHI-OH per mg of protein per min. Aldrin epoxidation and DHI hydroxylation activities of rhesus monkey liver biopsy and rat liver preparations were evaluated after phenobarbital treatment. The assay procedures can be used in protocols in which animals serve as their own controls."}
{"id": "PMID:3399", "title": "In vitro metabolism of 1-phenyl-2-propanone oxime in rat liver homogenates.", "content": "1-Phenyl-2-propanone oxime is a known in vitro metabolite of amphetamine. Further in vitro metabolism of this oxime with the 12,000g supernatant fraction from homogenized rat liver gave one major and two minor metabolites which were identified as 2-nitro-1-phenylpropane, benzyl alcohol, and 1-phenyl-2-propanone, respectively, by means of combined gas chromatography and mass spectrometry, and by comparison with authentic samples of each product.", "contents": "In vitro metabolism of 1-phenyl-2-propanone oxime in rat liver homogenates. 1-Phenyl-2-propanone oxime is a known in vitro metabolite of amphetamine. Further in vitro metabolism of this oxime with the 12,000g supernatant fraction from homogenized rat liver gave one major and two minor metabolites which were identified as 2-nitro-1-phenylpropane, benzyl alcohol, and 1-phenyl-2-propanone, respectively, by means of combined gas chromatography and mass spectrometry, and by comparison with authentic samples of each product."}
{"id": "PMID:3400", "title": "Anaerobic release of fluoride from halothane. Relationship to the binding of halothane metabolites to hepatic cellular constituents.", "content": "Halothane has been found to undergo a reductive defluorination. This reaction requires an active cytochrome P-450 system and NADPH, and is inducible by phenobarbital and polychlorinated biphenyls but not by methylcholanthrene. The fluoride release occurs only under low O2 tension, while high O2 tension results in the oxidation of halothane to trifluoroacetic acid, inorganic bromide, and chloride. The release of the inorganic fluoride is linear up to 60 min. Because the conditions required for fluoride release and the binding of a halothane metabolite to microsomal phospholipids are similar, the defluorinated halothane molecule is assumed to be involved with this binding. However, based on the amount of fluoride released, the defluorinated halothane metabolite represents only approximately 60% of the total amount of halothane metabolite bound, which suggests that more than one metabolite may be involved in the binding.", "contents": "Anaerobic release of fluoride from halothane. Relationship to the binding of halothane metabolites to hepatic cellular constituents. Halothane has been found to undergo a reductive defluorination. This reaction requires an active cytochrome P-450 system and NADPH, and is inducible by phenobarbital and polychlorinated biphenyls but not by methylcholanthrene. The fluoride release occurs only under low O2 tension, while high O2 tension results in the oxidation of halothane to trifluoroacetic acid, inorganic bromide, and chloride. The release of the inorganic fluoride is linear up to 60 min. Because the conditions required for fluoride release and the binding of a halothane metabolite to microsomal phospholipids are similar, the defluorinated halothane molecule is assumed to be involved with this binding. However, based on the amount of fluoride released, the defluorinated halothane metabolite represents only approximately 60% of the total amount of halothane metabolite bound, which suggests that more than one metabolite may be involved in the binding."}
{"id": "PMID:3401", "title": "Microsomal spectral properties and narcotic N-demethylase activity in methadone-dependent rats.", "content": "Rats were given access ad lib. to various concentrations (0.3 to 1.0 mg/ml) of methadone hydrochloride dissolved in sucrose solution. The N-demethylation of various narcotics was studied in hepatic preparations from methadone-consuming rats in order to determine if there was substrate specificity for the microsomal demethylase system. The Vmax for the N-demethylation of methadone, ethylmorphine, and meperidine was increased by 40-65%, whereas that for morphine N-demethylation was reduced to 55% of the control value. Additive or synergistic effects on microsomal cytochrome P-450 content were seen when methadone consumption was supplemented by administration of maximally inducing doses of either 3-methylcholanthrene (3-MC) or phenobarbital (PB). This suggested that there was an increase in a type of cytochrome P-450 which was independent of that induced by PB or 3-MC. The qualitative change in cytochrome P-450 reflected in the ethylisocyanide binding spectrum was also apparent after treatment with methadone, PB, or 3-MC, and the combination of methadone and PB exhibited effects that differed from PB alone. Two-substrate kinetic analysis with methadone and morphine as substrates indicated that more than one enzymic system may be involved in the N-demethylation reaction and that a common component of this N-demethylase system could not be induced with phenobarbital. However, methadone and meperidine seem to be demethylated by the same enzymic system.", "contents": "Microsomal spectral properties and narcotic N-demethylase activity in methadone-dependent rats. Rats were given access ad lib. to various concentrations (0.3 to 1.0 mg/ml) of methadone hydrochloride dissolved in sucrose solution. The N-demethylation of various narcotics was studied in hepatic preparations from methadone-consuming rats in order to determine if there was substrate specificity for the microsomal demethylase system. The Vmax for the N-demethylation of methadone, ethylmorphine, and meperidine was increased by 40-65%, whereas that for morphine N-demethylation was reduced to 55% of the control value. Additive or synergistic effects on microsomal cytochrome P-450 content were seen when methadone consumption was supplemented by administration of maximally inducing doses of either 3-methylcholanthrene (3-MC) or phenobarbital (PB). This suggested that there was an increase in a type of cytochrome P-450 which was independent of that induced by PB or 3-MC. The qualitative change in cytochrome P-450 reflected in the ethylisocyanide binding spectrum was also apparent after treatment with methadone, PB, or 3-MC, and the combination of methadone and PB exhibited effects that differed from PB alone. Two-substrate kinetic analysis with methadone and morphine as substrates indicated that more than one enzymic system may be involved in the N-demethylation reaction and that a common component of this N-demethylase system could not be induced with phenobarbital. However, methadone and meperidine seem to be demethylated by the same enzymic system."}
{"id": "PMID:3402", "title": "Metabolism of 2-(3-chloro-4(4-chlorobenzoyl)-phenyl)-as-triazine-3,5(2H,4H)-dione by the chicken.", "content": "The metabolism of the anticoccidial 2-[3-chloro-4-(4-chlorobenzoyl)phenyl]-as-triazine-3,-5(2H,4H)-dione (CP-25,415) was investigated in the chicken. It was shown that the predominant residue present in the chicken was 2-[3-chloro-4-(alpha-hydroxy-4-chlorobenzoyl)phenyl]-as-triazine-3,5(2H,4H)-dione (CP-25,641). A gas-liquid chromatographic assay for the analysis of CP-25,641 in biological fluids and tissues was developed which was rapid, accurate, and reproducible. Results of the analytical method correlated well with radiochemical measurements and were indicative of the total drug-related residues. The half-life of CP-25,641 in tissues was approximately 32 hr except in the kidney, where the half-life was approximately 40 hr due to urine retention by the kidneys. CP-25,641 was excreted without further change.", "contents": "Metabolism of 2-(3-chloro-4(4-chlorobenzoyl)-phenyl)-as-triazine-3,5(2H,4H)-dione by the chicken. The metabolism of the anticoccidial 2-[3-chloro-4-(4-chlorobenzoyl)phenyl]-as-triazine-3,-5(2H,4H)-dione (CP-25,415) was investigated in the chicken. It was shown that the predominant residue present in the chicken was 2-[3-chloro-4-(alpha-hydroxy-4-chlorobenzoyl)phenyl]-as-triazine-3,5(2H,4H)-dione (CP-25,641). A gas-liquid chromatographic assay for the analysis of CP-25,641 in biological fluids and tissues was developed which was rapid, accurate, and reproducible. Results of the analytical method correlated well with radiochemical measurements and were indicative of the total drug-related residues. The half-life of CP-25,641 in tissues was approximately 32 hr except in the kidney, where the half-life was approximately 40 hr due to urine retention by the kidneys. CP-25,641 was excreted without further change."}
{"id": "PMID:3403", "title": "Physiological disposition and metabolism of N-t-butylarterenol and its di-p-toluate ester (bitolterol) in the rat.", "content": "The metabolism and disposition of the bronchodilator, N-t-butylarterenol (tBA) and its di-p-toluate ester (bitolterol) were compared in the rat. Radioactivity was preferentially retained in lungs of rats compared with heart and blood after iv medication with tritium-labeled bitolterol, but was not retained in tissues after iv medication with [3H]tBA. After oral and iv medication with [3H]bitolterol, fecal radioactivity accounted for 24% of the dose and 65 and 79% of the radioactivity, respectively, was excreted in urine (0-72 hr). In comparison, urine radioactivity after oral and iv medication with [3H]tBA was 43 and 83% of the dose, respectively, and fecal radioactivity accounted for 43 or 23% of the dose, respectively (0-72 hr). Bitolterol was hydrolyzed in vitro to tBA by esterases found in various tissues including small intestine, liver, and plasma. Moreover, tBA was a substrate for catecholamine O-methyltransferase but not for monoamine oxidase. Similar metabolites were observed in urine samples of rats given either [3H]tBA or [3H]bitolterol. Urine metabolites were identified as free and conjugated forms of both tBA and 3-O-methyl-tBA.", "contents": "Physiological disposition and metabolism of N-t-butylarterenol and its di-p-toluate ester (bitolterol) in the rat. The metabolism and disposition of the bronchodilator, N-t-butylarterenol (tBA) and its di-p-toluate ester (bitolterol) were compared in the rat. Radioactivity was preferentially retained in lungs of rats compared with heart and blood after iv medication with tritium-labeled bitolterol, but was not retained in tissues after iv medication with [3H]tBA. After oral and iv medication with [3H]bitolterol, fecal radioactivity accounted for 24% of the dose and 65 and 79% of the radioactivity, respectively, was excreted in urine (0-72 hr). In comparison, urine radioactivity after oral and iv medication with [3H]tBA was 43 and 83% of the dose, respectively, and fecal radioactivity accounted for 43 or 23% of the dose, respectively (0-72 hr). Bitolterol was hydrolyzed in vitro to tBA by esterases found in various tissues including small intestine, liver, and plasma. Moreover, tBA was a substrate for catecholamine O-methyltransferase but not for monoamine oxidase. Similar metabolites were observed in urine samples of rats given either [3H]tBA or [3H]bitolterol. Urine metabolites were identified as free and conjugated forms of both tBA and 3-O-methyl-tBA."}
{"id": "PMID:3404", "title": "Physiological disposition and metabolism of (3H)bitolterol in man and dog.", "content": "The metabolism and disposition of bitolterol, the di-p-toluate ester of N-t-butylarterenol (tBA) was studied in man after a single oral dose and in dog after intraduodenal, iv, or oral administration. The mean (+/- SE) peak plasma radioactivity in man (dose, 70 mug/kg) was 180 +/- 18 ng equivalents of [3H]bitolterol per ml or approximately 11% of the dose, whereas peak plasma radioactivity in dog (dose, 200 mug/kg) was 144 +/- 23 ng equivalents per ml or approximately 4% of the dose. For both man and dog, the time for maximum plasma level of radioactivity varied from 0.5 to 2 hr. In man, only 1% of the plasma radioactivity represented intact [3H]bitolterol 1.0 hr after medication. In the dog, radioactivity was concentrated in lung tissue after iv administration of [3H]bitolterol. Recovery of intact [3H]bitolterol in lung at 4.5 hr ranged from 26 to 46% of total tissue radioactivity after iv dosage and from 4 to 14% total tissue radioactivity after intraduodenal administration. Radioactivity recovered in human urine and feces (0-72 hr) accounted for 86 and 8.1% of the dose, respectively. Recovery of radioactivity in dog urine and feces accounted for 58 and 23% of the dose, respectively, in the same time period. Radiochromatograms of urine samples from man and dog revealed similar patterns of metabolites including free and conjugated forms of both tBA and the 3-O-methyl metabolite, N-t-butylmetarterenol. The major radioactive components of the feces were bitolterol and tBA. The results indicate that bitolterol is absorbed orally and retained as the intact ester in lung. The prolonged bronchodilator activity of bitolterol is due to the slow release of the ester from lung and hydrolysis to tBA, an active beta2-adrenoceptor agonist. Pharmacological activity is terminated by metabolism of tBA via conjugation or 3-O-methylation.", "contents": "Physiological disposition and metabolism of (3H)bitolterol in man and dog. The metabolism and disposition of bitolterol, the di-p-toluate ester of N-t-butylarterenol (tBA) was studied in man after a single oral dose and in dog after intraduodenal, iv, or oral administration. The mean (+/- SE) peak plasma radioactivity in man (dose, 70 mug/kg) was 180 +/- 18 ng equivalents of [3H]bitolterol per ml or approximately 11% of the dose, whereas peak plasma radioactivity in dog (dose, 200 mug/kg) was 144 +/- 23 ng equivalents per ml or approximately 4% of the dose. For both man and dog, the time for maximum plasma level of radioactivity varied from 0.5 to 2 hr. In man, only 1% of the plasma radioactivity represented intact [3H]bitolterol 1.0 hr after medication. In the dog, radioactivity was concentrated in lung tissue after iv administration of [3H]bitolterol. Recovery of intact [3H]bitolterol in lung at 4.5 hr ranged from 26 to 46% of total tissue radioactivity after iv dosage and from 4 to 14% total tissue radioactivity after intraduodenal administration. Radioactivity recovered in human urine and feces (0-72 hr) accounted for 86 and 8.1% of the dose, respectively. Recovery of radioactivity in dog urine and feces accounted for 58 and 23% of the dose, respectively, in the same time period. Radiochromatograms of urine samples from man and dog revealed similar patterns of metabolites including free and conjugated forms of both tBA and the 3-O-methyl metabolite, N-t-butylmetarterenol. The major radioactive components of the feces were bitolterol and tBA. The results indicate that bitolterol is absorbed orally and retained as the intact ester in lung. The prolonged bronchodilator activity of bitolterol is due to the slow release of the ester from lung and hydrolysis to tBA, an active beta2-adrenoceptor agonist. Pharmacological activity is terminated by metabolism of tBA via conjugation or 3-O-methylation."}
{"id": "PMID:3405", "title": "Adriamycin metabolism in man. Evidence from urinary metabolites.", "content": "We studied the human metabolism of adriamycin by isolating and identifying urinary metabolites which retain adriamycin's specific fluorescence properties. Metabolites were extracted by adsorption to polystyrene polymeric sorbants, separated on silicic acid columns and purified by thin-layer chromatography. Structures were determined by comparative chromatography; infrared, fluorescence, and mass spectroscopy; and enzymatic and chemical degradation. Substances identified were adriamycinol, adriamycinol aglycone, adriamycin aglycone, deoxyadriamycin aglycone, deoxyadriamycinol aglycone, demethyldeoxyadriamycinol aglycone, demethyldeoxyadriamycinol aglycone 4-O-sulfate, and demethyldeoxyadriamycinol aglycone 4-O-beta-glucuronide. Other metabolites have been purified but not identified. Human metabolism of adriamycin involved carbonyl reduction, reductive glycosidic cleavage, hydrolytic glycosidic cleavage, O-demethylation, O-sulfation, and O-beta-glucuronidation. Carbonyl reduction was the major enzymatic conversion occurring in the human.", "contents": "Adriamycin metabolism in man. Evidence from urinary metabolites. We studied the human metabolism of adriamycin by isolating and identifying urinary metabolites which retain adriamycin's specific fluorescence properties. Metabolites were extracted by adsorption to polystyrene polymeric sorbants, separated on silicic acid columns and purified by thin-layer chromatography. Structures were determined by comparative chromatography; infrared, fluorescence, and mass spectroscopy; and enzymatic and chemical degradation. Substances identified were adriamycinol, adriamycinol aglycone, adriamycin aglycone, deoxyadriamycin aglycone, deoxyadriamycinol aglycone, demethyldeoxyadriamycinol aglycone, demethyldeoxyadriamycinol aglycone 4-O-sulfate, and demethyldeoxyadriamycinol aglycone 4-O-beta-glucuronide. Other metabolites have been purified but not identified. Human metabolism of adriamycin involved carbonyl reduction, reductive glycosidic cleavage, hydrolytic glycosidic cleavage, O-demethylation, O-sulfation, and O-beta-glucuronidation. Carbonyl reduction was the major enzymatic conversion occurring in the human."}
{"id": "PMID:3411", "title": "[Termination of pregnancy and perinatal mortality (author's transl)].", "content": "Elective induction was practised in 1875 of 10 537 deliveries (17.8%). Duration of delivery was, if anything, shortened after elective induction, compared with spontaneous delivery. There was no evidence of soft-tissue dystocias after elective induction. The Apgar score was 8-10 in 95.7% of children born after elective induction. pH of umbilical-artery blood in 95.7% of children after elective induction was greater than or equal to 7.2. There was a striking increase in the incidence of occiput posterior position with elective induction (2.7% of cases). The incidence of operative vaginal delivery was as frequent after elective as after all other forms of delivery. The incidence of section was 4.7% after elective induction, 11.5% in the entire series, intra-uterine asphyxia being an indication in 1.7%, compared with 2.5% for the total group. The frequency of operations was inversely proportional to the cervical index. Perinatal mortality was 0.53 per thousand (one case) after elective induction, 10.15 per thousand in the total group, 5.9 per thousand in those with indication for early induction. Perinatal mortality decreased from 23.0 per thousand to 7.2 per thousand from 1967 to 1974.", "contents": "[Termination of pregnancy and perinatal mortality (author's transl)]. Elective induction was practised in 1875 of 10 537 deliveries (17.8%). Duration of delivery was, if anything, shortened after elective induction, compared with spontaneous delivery. There was no evidence of soft-tissue dystocias after elective induction. The Apgar score was 8-10 in 95.7% of children born after elective induction. pH of umbilical-artery blood in 95.7% of children after elective induction was greater than or equal to 7.2. There was a striking increase in the incidence of occiput posterior position with elective induction (2.7% of cases). The incidence of operative vaginal delivery was as frequent after elective as after all other forms of delivery. The incidence of section was 4.7% after elective induction, 11.5% in the entire series, intra-uterine asphyxia being an indication in 1.7%, compared with 2.5% for the total group. The frequency of operations was inversely proportional to the cervical index. Perinatal mortality was 0.53 per thousand (one case) after elective induction, 10.15 per thousand in the total group, 5.9 per thousand in those with indication for early induction. Perinatal mortality decreased from 23.0 per thousand to 7.2 per thousand from 1967 to 1974."}
{"id": "PMID:3406", "title": "Binding of organic compounds to rat liver and lung.", "content": "The binding of various radioisotopically labeled organic compounds to rat liver and lung was investigated in vitro. Pieces of rat lung and slices of rat liver were incubated at 37 degrees C under a nitrogen atmosphere in a modified Krebs-Ringer phosphate solution (pH 7.4) CONTAININg the compound to be studied. Of the neutral compounds investigated, digitoxin, digoxin and dexamethasone were highly bound to both liver and lung tissue, whereas the degree of binding of amitrole, erythritol, and ouabain was 20% or less. The weak acids which were bound to the greatest extent in both liver and lung were phenobarbital, pentobarbital, and diphenylhydantoin. Barbital was poorly bound, and there was no evidence for the binding of 5,5-dimethyloxazolidine-2,4-dione or p-aminohippuric acid in either tissue. Binding of the cardiac glycosides and the barbiturates directly paralleled their lipid solubilities. The degree of binding of neutral compounds and weak acids to lung and liver tissue did not vary greatly with concentration, even though broad concentration ranges were studied. This was also true of the weak base morphine. On the other hand, the binding to liver and lung of the organic bases nicotine, pilocarpine, d-amphetamine, lidocaine, erythromycin, and chloroquine, did vary with concentration. The quaternary ammonium compound decamethonium was bound only to liver, and this binding also varied with concentration. Two additional quaternary ammonium compounds, tetraethylammonium and N1-methylnicotinamide, were not significantly bound to either tissue. Comparisons on the basis of equal content of solids revealed that the binding of diverse organic compounds in liver is greater than or equal to that in lung.", "contents": "Binding of organic compounds to rat liver and lung. The binding of various radioisotopically labeled organic compounds to rat liver and lung was investigated in vitro. Pieces of rat lung and slices of rat liver were incubated at 37 degrees C under a nitrogen atmosphere in a modified Krebs-Ringer phosphate solution (pH 7.4) CONTAININg the compound to be studied. Of the neutral compounds investigated, digitoxin, digoxin and dexamethasone were highly bound to both liver and lung tissue, whereas the degree of binding of amitrole, erythritol, and ouabain was 20% or less. The weak acids which were bound to the greatest extent in both liver and lung were phenobarbital, pentobarbital, and diphenylhydantoin. Barbital was poorly bound, and there was no evidence for the binding of 5,5-dimethyloxazolidine-2,4-dione or p-aminohippuric acid in either tissue. Binding of the cardiac glycosides and the barbiturates directly paralleled their lipid solubilities. The degree of binding of neutral compounds and weak acids to lung and liver tissue did not vary greatly with concentration, even though broad concentration ranges were studied. This was also true of the weak base morphine. On the other hand, the binding to liver and lung of the organic bases nicotine, pilocarpine, d-amphetamine, lidocaine, erythromycin, and chloroquine, did vary with concentration. The quaternary ammonium compound decamethonium was bound only to liver, and this binding also varied with concentration. Two additional quaternary ammonium compounds, tetraethylammonium and N1-methylnicotinamide, were not significantly bound to either tissue. Comparisons on the basis of equal content of solids revealed that the binding of diverse organic compounds in liver is greater than or equal to that in lung."}
{"id": "PMID:3407", "title": "Pharmacokinetics of digoxin in the rat.", "content": "Previous studies on the pharmacokinetics of 3H-digoxin in the rat have been based on total radioactivity in the plasma, even though the drug is extensively metabolized in this species. A comparison of total radioactivity vs. unchanged drug in rat plasma after administration of 3H-digoxin clearly showed the need to separate digoxin from its metabolites. The pharmacokinetics of digoxin were therefore examined using solvent extraction and thin-layer chromatography to isolate unchanged drug. Digoxin levels after a 1 mg/kg iv dose were measured in the plasma and urine of adult male rats in which the bile duct or the ureters had been ligated, as well as in sham-operated controls. In all cases, digoxin concentrations were best described by a two-compartment open model. Digoxin was rapidly eliminated from the plasma of controls, with a half-life of 2.5 hr, a volume of distribution of 3.6 liter/kg, and a renal clearance somewhat lower than the glomerular filtration rate. No significant change in these parameters was observed in rats with bile duct ligation. The total body clearance of 5.77 ml/min in the controls was reduced by only 10% in the bile duct-ligated rats. In animals with bilateral ureter ligation, the body clearance was reduced by 30% and the plasma half-life of digoxin was increased to 4 hr, although no significant change in the apparent volume of distribution was noted. Approximately 60% of the total body clearance was unaffected by bile duct and ureter ligations, and was assumed to be due to biotransformation. Biliary excretion was found to be important for digoxigenin bisdigitoxoside, inasmuch as rats with bile duct ligation showed elevated metabolite levels in the plasma as well as a 3-fold increase in renal excretion of the bisglycoside.", "contents": "Pharmacokinetics of digoxin in the rat. Previous studies on the pharmacokinetics of 3H-digoxin in the rat have been based on total radioactivity in the plasma, even though the drug is extensively metabolized in this species. A comparison of total radioactivity vs. unchanged drug in rat plasma after administration of 3H-digoxin clearly showed the need to separate digoxin from its metabolites. The pharmacokinetics of digoxin were therefore examined using solvent extraction and thin-layer chromatography to isolate unchanged drug. Digoxin levels after a 1 mg/kg iv dose were measured in the plasma and urine of adult male rats in which the bile duct or the ureters had been ligated, as well as in sham-operated controls. In all cases, digoxin concentrations were best described by a two-compartment open model. Digoxin was rapidly eliminated from the plasma of controls, with a half-life of 2.5 hr, a volume of distribution of 3.6 liter/kg, and a renal clearance somewhat lower than the glomerular filtration rate. No significant change in these parameters was observed in rats with bile duct ligation. The total body clearance of 5.77 ml/min in the controls was reduced by only 10% in the bile duct-ligated rats. In animals with bilateral ureter ligation, the body clearance was reduced by 30% and the plasma half-life of digoxin was increased to 4 hr, although no significant change in the apparent volume of distribution was noted. Approximately 60% of the total body clearance was unaffected by bile duct and ureter ligations, and was assumed to be due to biotransformation. Biliary excretion was found to be important for digoxigenin bisdigitoxoside, inasmuch as rats with bile duct ligation showed elevated metabolite levels in the plasma as well as a 3-fold increase in renal excretion of the bisglycoside."}
{"id": "PMID:3408", "title": "N-acetylation of drugs. Pharmacogenetic studies in rabbits selected for their acetylator characteristics.", "content": "Studies on acetylation of sulfadiazine, isoniazid, and p-aminobenzoic acid in selected lines of slow and rapid acetylator rabbits are described. Pedigree analysis of rabbits classified as slow or rapid sulfadiazine acetylators confirmed previous studies that the rate of sulfadiazine elimination (acetylation) is genetically controlled, with rapid elimination dominant over slow elimination of the drug. Pharmacokinetic studies in rabbits of specified sulfadiazine acetylator genotypes with isoniazid and p-aminobenzoic acid show that the rate of isoniazid elimination is under the same genetic control as is sulfadiazine, whereas the rate of p-aminobenzoic acid elimination is not. A new drug acetylation polymorphism, which controls the rate of enzymatic acetylation of p-aminobenzoic acid in peripheral blood cells and which is related to the sulfadiazine acetylation polymorphism, is described.", "contents": "N-acetylation of drugs. Pharmacogenetic studies in rabbits selected for their acetylator characteristics. Studies on acetylation of sulfadiazine, isoniazid, and p-aminobenzoic acid in selected lines of slow and rapid acetylator rabbits are described. Pedigree analysis of rabbits classified as slow or rapid sulfadiazine acetylators confirmed previous studies that the rate of sulfadiazine elimination (acetylation) is genetically controlled, with rapid elimination dominant over slow elimination of the drug. Pharmacokinetic studies in rabbits of specified sulfadiazine acetylator genotypes with isoniazid and p-aminobenzoic acid show that the rate of isoniazid elimination is under the same genetic control as is sulfadiazine, whereas the rate of p-aminobenzoic acid elimination is not. A new drug acetylation polymorphism, which controls the rate of enzymatic acetylation of p-aminobenzoic acid in peripheral blood cells and which is related to the sulfadiazine acetylation polymorphism, is described."}
{"id": "PMID:3414", "title": "Histidyl transfer ribonucleic acid synthetase from Salmonella typhimurium. Interaction with substrates and ATP analogues.", "content": "Structural requirements for substrate binding to histidyl-tRNA synthetase from Salmonella typhimurium have been investigated using ATP analogues. Ki values and the relative binding affinity of the enzyme for these analogues have been determined in the tRNA aminoacylation reaction. The enzyme is highly specific for ATP: no binding was found for GTP, CTP, TTP and UTP. dATP is a very poor substrate for acylation of tRNA, with a Km 40-fold higher than that of ATP. Binding of adenosine 5'-triphosphate requires interactions of the amino group of adenosine and the sugar moiety; the 2' and the 5' positions of the ribose appear to be essential for recognition; the phosphate groups enhance the binding. AMP is a noncompetitive inhibitor with ATP. The interaction of histidyl-tRNA synthetase, a dimeric enzyme, with histidine and ATP was examined by fluorescence measurements at equilibrium and by equilibrium dialysis. Binding with L-histidine is significantly tighter at pH 6 than at pH 7, while the ATP binding is independent of pH. The stoichiometry was measured at pH 6 than at pH 7, while the ATP binding is independent of pH. The stoichiometry was measured at pH 7.5 by equilibrium dialysis and is 1 mol ATP/mol enzyme and, variably, close to 2 or 1 mol histidine/mol enzyme.", "contents": "Histidyl transfer ribonucleic acid synthetase from Salmonella typhimurium. Interaction with substrates and ATP analogues. Structural requirements for substrate binding to histidyl-tRNA synthetase from Salmonella typhimurium have been investigated using ATP analogues. Ki values and the relative binding affinity of the enzyme for these analogues have been determined in the tRNA aminoacylation reaction. The enzyme is highly specific for ATP: no binding was found for GTP, CTP, TTP and UTP. dATP is a very poor substrate for acylation of tRNA, with a Km 40-fold higher than that of ATP. Binding of adenosine 5'-triphosphate requires interactions of the amino group of adenosine and the sugar moiety; the 2' and the 5' positions of the ribose appear to be essential for recognition; the phosphate groups enhance the binding. AMP is a noncompetitive inhibitor with ATP. The interaction of histidyl-tRNA synthetase, a dimeric enzyme, with histidine and ATP was examined by fluorescence measurements at equilibrium and by equilibrium dialysis. Binding with L-histidine is significantly tighter at pH 6 than at pH 7, while the ATP binding is independent of pH. The stoichiometry was measured at pH 6 than at pH 7, while the ATP binding is independent of pH. The stoichiometry was measured at pH 7.5 by equilibrium dialysis and is 1 mol ATP/mol enzyme and, variably, close to 2 or 1 mol histidine/mol enzyme."}
{"id": "PMID:3415", "title": "[The coupling of beta1-24-corticotropin to the adenylate-cylase system in rat adipocytes. Evidence for hormone-nucleotides interaction (author's transl)].", "content": "The general aim was to define some of the most important parameters involved in the coupling step between the synthetic analog of adrenocoricotropin hormone  (beta1-24-corticotropin tetracosa peptide) and the catalytic unit of the adenylate-cyclase system of fat cells.  These studies were performed with a purified plasma membrane fraction from rat adipose tissue.  In this regard, some effects of ions, pH, and nucleotides (ATP nad GTP) on this hormone sensitive system were studied A simple model based on a random association process of reactants yeilded a statisfactory approximation of the kinetic data.  In contract to results obtained by two other groups, which were analyzed by De Haen, no evidence was found for a regulation of the adenylate-cyclase activity by the adenosine triphosphate which was not complexed to magnesium...", "contents": "[The coupling of beta1-24-corticotropin to the adenylate-cylase system in rat adipocytes. Evidence for hormone-nucleotides interaction (author's transl)]. The general aim was to define some of the most important parameters involved in the coupling step between the synthetic analog of adrenocoricotropin hormone  (beta1-24-corticotropin tetracosa peptide) and the catalytic unit of the adenylate-cyclase system of fat cells.  These studies were performed with a purified plasma membrane fraction from rat adipose tissue.  In this regard, some effects of ions, pH, and nucleotides (ATP nad GTP) on this hormone sensitive system were studied A simple model based on a random association process of reactants yeilded a statisfactory approximation of the kinetic data.  In contract to results obtained by two other groups, which were analyzed by De Haen, no evidence was found for a regulation of the adenylate-cyclase activity by the adenosine triphosphate which was not complexed to magnesium..."}
{"id": "PMID:3416", "title": "Ion-binding to phospholipids. Interaction of calcium with phosphatidylserine.", "content": "The binding of Ca2+ to monolayers and bilayers of phosphatidylserine has been investigated as a function of pH, ionic strength (NaCl concentration) and Ca2+ concentration using surface and colloid chemical techniques. The molar ratio of lipid to bound calcium decreases to 2 as the Ca2+ concentration is increased to about 0.1 mM. At [Ca2+] greater than 0.1 mM a 1:1 complex is formed. The apparent binding constant Ka ranges from about approximately 10(6) - 10(4) l/mol depending on the Ca2+ concentration. After allowing for electrostatic effects and neighbour group interactions, the intrinsic binding constant Ki of the phosphorylserine polar group at pH 7 (I = 0.01 M), where it carries a net negative charge of one, is approximately 10(4) l/mol; consistent values for Ki were obtained using several independent approaches. Ka for Ca2+ binding decreases with increasing NaCl concentration because the monovalent cations compete with Ca2+ for the same binding site. Na+ and K+ are equally effective in displacing 45Ca2+ adsorbed to monolayers of phosphatidylserine, both with respect to the kinetics and the equilibrium of the displacement. Ka for the reaction between phosphatidylserine and monovalent cations is about 10(3)-fold smaller than that of Ca2+. An investigation of the binding of Mn2+ to phosphatidylserine by both surface chemical and nuclear magnetic resonance methods shows that this cation has a similar binding constant to that of Ca2+. The Ca2+-binding capabilities of monolayers containing only carboxyl groups (i.e. arachidic acid) and phosphodiester groups (i.e. dicetyl phosphate) have also been determined; the apparent pK for the - COOH group in monolayers is larger than or equal to 9 and that for the phosphodiester group is less than 4. Since these groups do not retain the same pK values when they are in close proximity in the phosphorylserine group, the relative contributions of the two groups to the binding of Ca2+ to phosphatidylserine is not obvious.", "contents": "Ion-binding to phospholipids. Interaction of calcium with phosphatidylserine. The binding of Ca2+ to monolayers and bilayers of phosphatidylserine has been investigated as a function of pH, ionic strength (NaCl concentration) and Ca2+ concentration using surface and colloid chemical techniques. The molar ratio of lipid to bound calcium decreases to 2 as the Ca2+ concentration is increased to about 0.1 mM. At [Ca2+] greater than 0.1 mM a 1:1 complex is formed. The apparent binding constant Ka ranges from about approximately 10(6) - 10(4) l/mol depending on the Ca2+ concentration. After allowing for electrostatic effects and neighbour group interactions, the intrinsic binding constant Ki of the phosphorylserine polar group at pH 7 (I = 0.01 M), where it carries a net negative charge of one, is approximately 10(4) l/mol; consistent values for Ki were obtained using several independent approaches. Ka for Ca2+ binding decreases with increasing NaCl concentration because the monovalent cations compete with Ca2+ for the same binding site. Na+ and K+ are equally effective in displacing 45Ca2+ adsorbed to monolayers of phosphatidylserine, both with respect to the kinetics and the equilibrium of the displacement. Ka for the reaction between phosphatidylserine and monovalent cations is about 10(3)-fold smaller than that of Ca2+. An investigation of the binding of Mn2+ to phosphatidylserine by both surface chemical and nuclear magnetic resonance methods shows that this cation has a similar binding constant to that of Ca2+. The Ca2+-binding capabilities of monolayers containing only carboxyl groups (i.e. arachidic acid) and phosphodiester groups (i.e. dicetyl phosphate) have also been determined; the apparent pK for the - COOH group in monolayers is larger than or equal to 9 and that for the phosphodiester group is less than 4. Since these groups do not retain the same pK values when they are in close proximity in the phosphorylserine group, the relative contributions of the two groups to the binding of Ca2+ to phosphatidylserine is not obvious."}
{"id": "PMID:3419", "title": "Action of H1 and H2 inhibitors on the response of histamine sensitive adenyly cyclase from guinea-pig mucosa.", "content": "In the guinea-pig, it has been shown that homogenates of mucosa from the fundus contain an adenylyl cyclase system that is activated by histamine as well as by prostaglandins PGE1 and PGA1. The effects of burimamide, an H2-inhibitor, and mepyramine and chlorpheniramide, both H1-inhibitors, were tested. Both H1 and H2 inhibitors behaved kinetically as competitive inhibitors of histamine, but the Km derived for burimamide (2.5 - 4.1 . 10(-5)) was significantly lower than that for either chlorpheniramine (0.9 - 1.9 . 10(-4)) or mepyramine (1.3 - 1.4 . 10(-4)). On the other hand none of the three inhibitors influenced the cyclase activation by PGE1 and PGA1. These results suggest that there are at least two types of receptors in the preparation studied, one responsive to histamine and the other to the prostaglandins, and that the specificity of H1- and H2-receptors is not absolute in the broken cell preparation.", "contents": "Action of H1 and H2 inhibitors on the response of histamine sensitive adenyly cyclase from guinea-pig mucosa. In the guinea-pig, it has been shown that homogenates of mucosa from the fundus contain an adenylyl cyclase system that is activated by histamine as well as by prostaglandins PGE1 and PGA1. The effects of burimamide, an H2-inhibitor, and mepyramine and chlorpheniramide, both H1-inhibitors, were tested. Both H1 and H2 inhibitors behaved kinetically as competitive inhibitors of histamine, but the Km derived for burimamide (2.5 - 4.1 . 10(-5)) was significantly lower than that for either chlorpheniramine (0.9 - 1.9 . 10(-4)) or mepyramine (1.3 - 1.4 . 10(-4)). On the other hand none of the three inhibitors influenced the cyclase activation by PGE1 and PGA1. These results suggest that there are at least two types of receptors in the preparation studied, one responsive to histamine and the other to the prostaglandins, and that the specificity of H1- and H2-receptors is not absolute in the broken cell preparation."}
{"id": "PMID:3420", "title": "Anti-arrhythmic action of nadolol, a beta-adrenergic receptor blocking agent.", "content": "The anti-arrhythmic action of 2,3-cis-1,2,3,4-tetrahydro-5-[(2-hydroxy-3-tert-butylamino)propoxy]2,3-naphthalenediol (nadolol) was evaluated and compared with that of propranolol in several experimental models of cardiac arrhythmias. Both nadolol and propranolol antagonized isoproterenol-induced tachycardia and ouabain-induced arrhythmias in cats, antagonized coronary artery ligation-induced ventricular fibrillation and suppressed ventricular ectopic activity during vagal stimulation in dogs. In contrast to propranolol, nadolol was considerably weaker in suppressing existing digoxin-induced arrhythmias, lacked local anesthetic activity and did not depress the heart in dogs. Because of these findings, it is concluded that the anti-arrhythmic activity of nadolol is apparently related to blockade of beta-adrenergic receptors.", "contents": "Anti-arrhythmic action of nadolol, a beta-adrenergic receptor blocking agent. The anti-arrhythmic action of 2,3-cis-1,2,3,4-tetrahydro-5-[(2-hydroxy-3-tert-butylamino)propoxy]2,3-naphthalenediol (nadolol) was evaluated and compared with that of propranolol in several experimental models of cardiac arrhythmias. Both nadolol and propranolol antagonized isoproterenol-induced tachycardia and ouabain-induced arrhythmias in cats, antagonized coronary artery ligation-induced ventricular fibrillation and suppressed ventricular ectopic activity during vagal stimulation in dogs. In contrast to propranolol, nadolol was considerably weaker in suppressing existing digoxin-induced arrhythmias, lacked local anesthetic activity and did not depress the heart in dogs. Because of these findings, it is concluded that the anti-arrhythmic activity of nadolol is apparently related to blockade of beta-adrenergic receptors."}
{"id": "PMID:3421", "title": "Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity.", "content": "The effects of local injections of drugs into terminal areas of the mesolimbic dopamine system were investigated. Bilateral administration of dopamine, but not of noradrenaline and serotonin, into the nucleus accumbens of non-pretreated rats resulted in stimulation of locomotor activity. No clear or only minor effects were seen after injections of the dopamine metabolites 3-methoxytyramine, DOPAC and HVA and after injections of media with different pH and osmolality. d-Amphetamine proved more effective than dopamine in producing locomotor stimulation, whereas both stimulant and depressant effects were observed following injection of apomorphine into the nucleus accumbens. ET 495 and the noradrenaline agonists clonidine, phenylephrine and isoprenaline did not enhance locomotor activity, but theophylline was effective. Pretreatment with haloperidol, but not with clozapine, significantly reduced the effects of dopamine and theophylline. Locomotor stimulation was also found following bilateral administration of dopamine, d-amphetamine and apomorphine into the tuberculum olfactorium, whereas noradrenaline, serotonin and ET 495 produced no, or rather depressant effects. These results provide further evidence for an important role of the mesolimbic dopamine system with respect to locomotor activity.", "contents": "Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. The effects of local injections of drugs into terminal areas of the mesolimbic dopamine system were investigated. Bilateral administration of dopamine, but not of noradrenaline and serotonin, into the nucleus accumbens of non-pretreated rats resulted in stimulation of locomotor activity. No clear or only minor effects were seen after injections of the dopamine metabolites 3-methoxytyramine, DOPAC and HVA and after injections of media with different pH and osmolality. d-Amphetamine proved more effective than dopamine in producing locomotor stimulation, whereas both stimulant and depressant effects were observed following injection of apomorphine into the nucleus accumbens. ET 495 and the noradrenaline agonists clonidine, phenylephrine and isoprenaline did not enhance locomotor activity, but theophylline was effective. Pretreatment with haloperidol, but not with clozapine, significantly reduced the effects of dopamine and theophylline. Locomotor stimulation was also found following bilateral administration of dopamine, d-amphetamine and apomorphine into the tuberculum olfactorium, whereas noradrenaline, serotonin and ET 495 produced no, or rather depressant effects. These results provide further evidence for an important role of the mesolimbic dopamine system with respect to locomotor activity."}
{"id": "PMID:3426", "title": "Effect of PGE1 on lipogenesis in perfused rat liver.", "content": "In perfused livers of 24 hour-fasted rats, PGE1 (prostaglandin E1) infused continuously into the perfusate, was found to cause a 45% increase in the incorporation of 1-14C acetate into liver fatty acids. PGE1 was found to have no effect, however, on the activity of the key lipogenic enzymes.", "contents": "Effect of PGE1 on lipogenesis in perfused rat liver. In perfused livers of 24 hour-fasted rats, PGE1 (prostaglandin E1) infused continuously into the perfusate, was found to cause a 45% increase in the incorporation of 1-14C acetate into liver fatty acids. PGE1 was found to have no effect, however, on the activity of the key lipogenic enzymes."}
{"id": "PMID:3428", "title": "Influence of mono- and multivalent cations on the electrokinetic properties of normal human lymphoid and burkitt lymphoma cells.", "content": "Various mono- and multivalent cations, at constant ionic strength, affected the surface electrokinetic properties of normal human lymphoid and Burkitt lymphoma cells in a manner which reflected more the physicochemical properties and binding affinities of the cation than its valence. The effect was expressed in the changes of the magnitude of the net surface charge and in the shift of the isoelectric point of the surface. These changes were greater at the surface of Burkitt's lymphoma cells than at the surface of their normal cell-line counterparts.", "contents": "Influence of mono- and multivalent cations on the electrokinetic properties of normal human lymphoid and burkitt lymphoma cells. Various mono- and multivalent cations, at constant ionic strength, affected the surface electrokinetic properties of normal human lymphoid and Burkitt lymphoma cells in a manner which reflected more the physicochemical properties and binding affinities of the cation than its valence. The effect was expressed in the changes of the magnitude of the net surface charge and in the shift of the isoelectric point of the surface. These changes were greater at the surface of Burkitt's lymphoma cells than at the surface of their normal cell-line counterparts."}
{"id": "PMID:3435", "title": "1,8-naphthyridine derivatives: synthesis and pharmacological evaluation of beta-receptor blocking activity.", "content": "The synthesis of a number of 1-alkyl-7-(2-hydroxy-3-alkylaminopropoxy)-1,8-naphthyridin-2-ones is described. The compounds studied were prepared by reaction of 1-alkyl-7-hydroxy-1,8-naphthyridin-2-ones with epichlorohydrin. The substituted epoxy intermediates obtained were allowed to react with amines and gave the desired products. All the compunds prepared were devoid of beta-blocking activity.", "contents": "1,8-naphthyridine derivatives: synthesis and pharmacological evaluation of beta-receptor blocking activity. The synthesis of a number of 1-alkyl-7-(2-hydroxy-3-alkylaminopropoxy)-1,8-naphthyridin-2-ones is described. The compounds studied were prepared by reaction of 1-alkyl-7-hydroxy-1,8-naphthyridin-2-ones with epichlorohydrin. The substituted epoxy intermediates obtained were allowed to react with amines and gave the desired products. All the compunds prepared were devoid of beta-blocking activity."}
{"id": "PMID:3433", "title": "[Pharmacology of methvin--a new ganglionic blocking preparation of short-term effect].", "content": "Methvin (vincanin chlormethylate) is an active ganglion blocking agent of a short-term action. As regards its gangliolytic action it is approximately 6 times superior to afronad. In test animals the drug produces a well-marked and short-term (easily controllable) hypotensive effect, without causing any histamine-like and direct vasodilation action. When used in relatively high doses methvin blocks the neuro-muscular conduction, potentiates the action of major muscle relaxants. A study of methvin in clinical conditions confirmed its high gangliolytic activity previously revealed in experiments.", "contents": "[Pharmacology of methvin--a new ganglionic blocking preparation of short-term effect]. Methvin (vincanin chlormethylate) is an active ganglion blocking agent of a short-term action. As regards its gangliolytic action it is approximately 6 times superior to afronad. In test animals the drug produces a well-marked and short-term (easily controllable) hypotensive effect, without causing any histamine-like and direct vasodilation action. When used in relatively high doses methvin blocks the neuro-muscular conduction, potentiates the action of major muscle relaxants. A study of methvin in clinical conditions confirmed its high gangliolytic activity previously revealed in experiments."}
{"id": "PMID:3434", "title": "[Heightened anticholinesterase activity of chlorophos in its interaction with the TMB-4 reactivator in vitro].", "content": "Experiments in vitro demonstrated that a thermostatic treatment of an aqueous chlorophos solution at 38 degrees is attended by its increased cholinesterase activity. The speed of the process is much higher in an alkaline medium. A joint incubation of chlorophos with the TMB-4 reactivator of pH of 7.5 and 38 degrees not only fails to result in decomposition of the poison, but on the contrary, tends to speed up the progressive accretion of the inhibitory properties of this organophosphorus compound. The author considers the data obtained as one of the proofs pointing to the formation during direct interaction of TMB-4 with chlorophos or the product of its transformation of a stable complex appearing to be a powerful anticholinesterase agent.", "contents": "[Heightened anticholinesterase activity of chlorophos in its interaction with the TMB-4 reactivator in vitro]. Experiments in vitro demonstrated that a thermostatic treatment of an aqueous chlorophos solution at 38 degrees is attended by its increased cholinesterase activity. The speed of the process is much higher in an alkaline medium. A joint incubation of chlorophos with the TMB-4 reactivator of pH of 7.5 and 38 degrees not only fails to result in decomposition of the poison, but on the contrary, tends to speed up the progressive accretion of the inhibitory properties of this organophosphorus compound. The author considers the data obtained as one of the proofs pointing to the formation during direct interaction of TMB-4 with chlorophos or the product of its transformation of a stable complex appearing to be a powerful anticholinesterase agent."}
{"id": "PMID:3445", "title": "The temperature, pH, and partial pressure of oxygen in the cervix and uterus of women and uterus of rats during the cycle.", "content": "Changes in the temperature, pH, and partial pressure of oxygen (PO2) in the cervical canal and cavum uteri were measured in women with or without an intrauterine device and in the uteri of rats throughout the cycle. Only the PO2 exhibited significant variations, rising during the ovulatory phase in both cervices of women and uteri in rats. It is speculated that the rise in PO2 is related to the function of these organs as reservoirs for spermatozoa.", "contents": "The temperature, pH, and partial pressure of oxygen in the cervix and uterus of women and uterus of rats during the cycle. Changes in the temperature, pH, and partial pressure of oxygen (PO2) in the cervical canal and cavum uteri were measured in women with or without an intrauterine device and in the uteri of rats throughout the cycle. Only the PO2 exhibited significant variations, rising during the ovulatory phase in both cervices of women and uteri in rats. It is speculated that the rise in PO2 is related to the function of these organs as reservoirs for spermatozoa."}
{"id": "PMID:3446", "title": "[Responses of small intestine tissue chemoreceptors to change in the pCO2, pH and (HCO3-) in perfusion solutions].", "content": "Perfusion of the small intestine of anesthetized cats with a solution having excessive CO2 and H+ concentration (pCO2 60 mm Hg; pH; 7.2; [HCO3-] 25 MM) produced a threshold reflex increase in the blood pressure. The subsequent increase of pCO2 to 380 mm Hg and decrease of pH to 6.4 evoked a gradual raise of the blood pressure (8.0+/-0.6 mm Hg) followed by the sharp increase of pressor reflexes amplitude within the range of pH 6.4--6.1. Tissue receptors were found to be essentially sensitive to solutions imitating metabolic acidosis (decrease of [HCO3-] within the physiological range of pH changes (pH 7.1--6.8). Solutions with pH 6.4--6.1 imitating respiratory acidosis (increase of pCO2) were more effective than those imitating metabolic acidosis. The possible role of interstitial pH changes in responses of the tissue chemoreceptors to CO2, is discussed.", "contents": "[Responses of small intestine tissue chemoreceptors to change in the pCO2, pH and (HCO3-) in perfusion solutions]. Perfusion of the small intestine of anesthetized cats with a solution having excessive CO2 and H+ concentration (pCO2 60 mm Hg; pH; 7.2; [HCO3-] 25 MM) produced a threshold reflex increase in the blood pressure. The subsequent increase of pCO2 to 380 mm Hg and decrease of pH to 6.4 evoked a gradual raise of the blood pressure (8.0+/-0.6 mm Hg) followed by the sharp increase of pressor reflexes amplitude within the range of pH 6.4--6.1. Tissue receptors were found to be essentially sensitive to solutions imitating metabolic acidosis (decrease of [HCO3-] within the physiological range of pH changes (pH 7.1--6.8). Solutions with pH 6.4--6.1 imitating respiratory acidosis (increase of pCO2) were more effective than those imitating metabolic acidosis. The possible role of interstitial pH changes in responses of the tissue chemoreceptors to CO2, is discussed."}
{"id": "PMID:3448", "title": "Identification of dimethylnitrosoamine metabolites in vitro.", "content": "The incubation of dimethylnitrosoamine (DMNA) in the presence of rat liver microsomes leads to production of formaldehyde, formic acid, methylamine, and N-methylhydrazine. When pH 5-enzymes are added to the medium there is also the formation of N-methylhydroxylamide and N,N-dimethylhydrazine. The last compound is the only metabolite produced, to a lesser extent, by the pH 5-enzymes. Thus, the denitrosated or non-denitrosated metabolites are produced either by an oxidative dealkylation and by a reduction of DMNA, catalysed by microsomal and cellular soluble enzymes.", "contents": "Identification of dimethylnitrosoamine metabolites in vitro. The incubation of dimethylnitrosoamine (DMNA) in the presence of rat liver microsomes leads to production of formaldehyde, formic acid, methylamine, and N-methylhydrazine. When pH 5-enzymes are added to the medium there is also the formation of N-methylhydroxylamide and N,N-dimethylhydrazine. The last compound is the only metabolite produced, to a lesser extent, by the pH 5-enzymes. Thus, the denitrosated or non-denitrosated metabolites are produced either by an oxidative dealkylation and by a reduction of DMNA, catalysed by microsomal and cellular soluble enzymes."}
{"id": "PMID:3449", "title": "Degradation of dimethylnitrosoamine catalysed by physical and chemical agents.", "content": "Decomposition of dimethylnitrosoamine (DMNA) by chemical and physical agents was further investigated. Both photoirradiation with sunlight or ultraviolet ray and reductive reactions under acid conditions (likely occurring in the stomach) led to the formation of formaldehyde, formic acid, and N-methydrazine, in addition to denitrosated compounds such as methylamine, dimethylamine, and N-methylhydroxylamine. N-Methylhydrazine was the only compound which was not detected by photoirradiation under neutral conditions. The agreement between physiochemical and metabolic degradation products and the possible biological meaning are discussed together with the problem of environmental contamination by the nitroso compound.", "contents": "Degradation of dimethylnitrosoamine catalysed by physical and chemical agents. Decomposition of dimethylnitrosoamine (DMNA) by chemical and physical agents was further investigated. Both photoirradiation with sunlight or ultraviolet ray and reductive reactions under acid conditions (likely occurring in the stomach) led to the formation of formaldehyde, formic acid, and N-methydrazine, in addition to denitrosated compounds such as methylamine, dimethylamine, and N-methylhydroxylamine. N-Methylhydrazine was the only compound which was not detected by photoirradiation under neutral conditions. The agreement between physiochemical and metabolic degradation products and the possible biological meaning are discussed together with the problem of environmental contamination by the nitroso compound."}
{"id": "PMID:3450", "title": "Properties of aryl hydrocarbon hydroxylase in microsomes of Morris hepatoma 5123D and the host liver.", "content": "Properties of aryl hydrocarbon hydroxylase in the microsomes were compared between Morris hepatoma 5123D and the host liver from rats bearing this tumor. Requirement of NADPH for the assay of the enzyme activity was observed, compared to that of NADH, and also the additive effect of NADH on the requirement of NADPH was found in the tumor and liver. Curve of pH optimum of the enzyme activity in tumor and liver differed between the rats treated with corn oil and those with 3-methylcholanthrene, indicating a slight shift of the peak value to alkaline pH in the latter. The same values of the apparent Km for NADPH and NADH were shown for the enzyme from the liver and tumor even 24 hr after the treatment with 3-methylcholanthrene, but a difference in the apparent Km for benzo[a]pyrene was demonstrated between the tumor and the host liver, showing 3.6 approximately 6.6 muM in the former and 9.1 approximately 20 muM in the latter. By the addition of 7,8- or 5,6-benzoflavone to the assay medium for the tumor, the induced enzyme was inhibited noncompetitively, and the constitutive enzyme was enhanced, as demonstrated in the host liver. As observed in the induced enzyme in both tissues, cyclohexene oxide and 1,1,1-trichloropropane oxide slightly increased the activity of the constitutive enzyme in the tumor, in contrast to its inhibition in the host liver.", "contents": "Properties of aryl hydrocarbon hydroxylase in microsomes of Morris hepatoma 5123D and the host liver. Properties of aryl hydrocarbon hydroxylase in the microsomes were compared between Morris hepatoma 5123D and the host liver from rats bearing this tumor. Requirement of NADPH for the assay of the enzyme activity was observed, compared to that of NADH, and also the additive effect of NADH on the requirement of NADPH was found in the tumor and liver. Curve of pH optimum of the enzyme activity in tumor and liver differed between the rats treated with corn oil and those with 3-methylcholanthrene, indicating a slight shift of the peak value to alkaline pH in the latter. The same values of the apparent Km for NADPH and NADH were shown for the enzyme from the liver and tumor even 24 hr after the treatment with 3-methylcholanthrene, but a difference in the apparent Km for benzo[a]pyrene was demonstrated between the tumor and the host liver, showing 3.6 approximately 6.6 muM in the former and 9.1 approximately 20 muM in the latter. By the addition of 7,8- or 5,6-benzoflavone to the assay medium for the tumor, the induced enzyme was inhibited noncompetitively, and the constitutive enzyme was enhanced, as demonstrated in the host liver. As observed in the induced enzyme in both tissues, cyclohexene oxide and 1,1,1-trichloropropane oxide slightly increased the activity of the constitutive enzyme in the tumor, in contrast to its inhibition in the host liver."}
{"id": "PMID:3451", "title": "Electronic interaction of carcinogenic and noncarcinogenic benz(c)acridines and DNA.", "content": "Electronic interaction of DNA with nine benzacridine derivatives was studied. The interaction system of these benzacridines and DNA was found to show a marked hypochromism in the ultraviolet region. The orderly double helical structure of DNA was found to play an essential role in this spectroscopic change. A high concentration of the interactant, low environmental ionic strength, low pH, and low temperature were beneficial in this interaction. The degree of hypochromism expressed by the integrated and pKa of the benzacridines were found to be in parallel. The hypochromism of the interaction system, in which the carcinogenic benz[c]acridine derivatives took part, was larger than that of the system in which the noncarcinogenic derivatives were involved.", "contents": "Electronic interaction of carcinogenic and noncarcinogenic benz(c)acridines and DNA. Electronic interaction of DNA with nine benzacridine derivatives was studied. The interaction system of these benzacridines and DNA was found to show a marked hypochromism in the ultraviolet region. The orderly double helical structure of DNA was found to play an essential role in this spectroscopic change. A high concentration of the interactant, low environmental ionic strength, low pH, and low temperature were beneficial in this interaction. The degree of hypochromism expressed by the integrated and pKa of the benzacridines were found to be in parallel. The hypochromism of the interaction system, in which the carcinogenic benz[c]acridine derivatives took part, was larger than that of the system in which the noncarcinogenic derivatives were involved."}
{"id": "PMID:3452", "title": "Purification of an immunosuppressive principle from Ehrlich carcinoma ascites.", "content": "An immunosuppressive factor was purified from Ehrlich carcinoma ascites by the combination of ultrafiltration and Sephadex chromatography. The resulting product showed 50% reduction in the number of splenic plaque-forming cells in mice immunized with sheep red blood cells when as low as 50 mug dose was given twice intraperitoneally before erythrocyte injection. The molecular size of the product was between 30,000 and 100,000, and it was relatively heat unstable.", "contents": "Purification of an immunosuppressive principle from Ehrlich carcinoma ascites. An immunosuppressive factor was purified from Ehrlich carcinoma ascites by the combination of ultrafiltration and Sephadex chromatography. The resulting product showed 50% reduction in the number of splenic plaque-forming cells in mice immunized with sheep red blood cells when as low as 50 mug dose was given twice intraperitoneally before erythrocyte injection. The molecular size of the product was between 30,000 and 100,000, and it was relatively heat unstable."}
{"id": "PMID:3453", "title": "[Inhalation analgesia with methoxyfluran (penthrane) in obstetrics (author's transl)].", "content": "In 105 normal spontaneous deliveries the effect of inhalation analgesia with Methoxyfluran (Penthrane) was studied. Penthrane was administered intermittently with the Penthrane oxilator (Rod inhalator of Abbott). The initial concentration was 0.25 volume%. The maximal concentration was 0.35 volume% of Penthrane. Fetal monitoring records were obtained in all deliveries. In 49 cases (46.7%) intra- and post-partum microblood studies were obtained. In 85 women (81.0%) the result of the analgesia was good. Nausea occurred in 21 women (20%). There were no abnormal fetal monitoring patterns. The Apgar scores of the newborns were between 8 and 10. The actual pH's were between 7.24 and 7.41. The third stage of labour was normal in all cases.", "contents": "[Inhalation analgesia with methoxyfluran (penthrane) in obstetrics (author's transl)]. In 105 normal spontaneous deliveries the effect of inhalation analgesia with Methoxyfluran (Penthrane) was studied. Penthrane was administered intermittently with the Penthrane oxilator (Rod inhalator of Abbott). The initial concentration was 0.25 volume%. The maximal concentration was 0.35 volume% of Penthrane. Fetal monitoring records were obtained in all deliveries. In 49 cases (46.7%) intra- and post-partum microblood studies were obtained. In 85 women (81.0%) the result of the analgesia was good. Nausea occurred in 21 women (20%). There were no abnormal fetal monitoring patterns. The Apgar scores of the newborns were between 8 and 10. The actual pH's were between 7.24 and 7.41. The third stage of labour was normal in all cases."}
{"id": "PMID:3456", "title": "Post-prandial changes in PH and electrolyte concentration, in the upper jejunum after truncal vagotomy and drainage in man.", "content": "The changes in pH and concentration of electrolytes in the jejunal lumen after a hypertonic fluid meal have been studied after truncal vagotomy and drainage, with and without diarrhoea. The results show that, in these respects, there are no specific changes in the jejunal content associated with post-vagotomy diarrhoea, but that these measurements are markedly affected by the completeness of vagotomy, as judged by the insulin test.", "contents": "Post-prandial changes in PH and electrolyte concentration, in the upper jejunum after truncal vagotomy and drainage in man. The changes in pH and concentration of electrolytes in the jejunal lumen after a hypertonic fluid meal have been studied after truncal vagotomy and drainage, with and without diarrhoea. The results show that, in these respects, there are no specific changes in the jejunal content associated with post-vagotomy diarrhoea, but that these measurements are markedly affected by the completeness of vagotomy, as judged by the insulin test."}
{"id": "PMID:3457", "title": "Vitamin B12 absorption--a study of intraluminal events in control subjects and patients with tropical sprue.", "content": "The intraluminal fate of orally administered radioactive vitamin B12 has been studied in control subjects with normal vitamin B12 absorption and those with vitamin B12 malabsorption due to tropical sprue. In control subjects 1 to 21% of the dose was bound to sedimentable material and 37 to 75% was bound to immunoreactive intrinsic factor. In subjects with vitamin B12 malabsorption due to tropical sprue, the results were identical with the control subjects. Bacteriological studies showed a statistically significant correlation between both the number of flora in the jejunum and the number of bacteroides in both the jejunum and ileum and vitamin B12 malabsorption. In patients with tropical sprue who have normal intrinsic factor secretion, the vitamin B12 absorptive defect is not due to binding of the vitamin to bacteria or to alteration to the intrinsic factor vitamin B12 complex in the intestinal lumen. The lesion appears to be one of the mucosal cell receptors or of the cells themselves, possibly caused by bacterial toxins.", "contents": "Vitamin B12 absorption--a study of intraluminal events in control subjects and patients with tropical sprue. The intraluminal fate of orally administered radioactive vitamin B12 has been studied in control subjects with normal vitamin B12 absorption and those with vitamin B12 malabsorption due to tropical sprue. In control subjects 1 to 21% of the dose was bound to sedimentable material and 37 to 75% was bound to immunoreactive intrinsic factor. In subjects with vitamin B12 malabsorption due to tropical sprue, the results were identical with the control subjects. Bacteriological studies showed a statistically significant correlation between both the number of flora in the jejunum and the number of bacteroides in both the jejunum and ileum and vitamin B12 malabsorption. In patients with tropical sprue who have normal intrinsic factor secretion, the vitamin B12 absorptive defect is not due to binding of the vitamin to bacteria or to alteration to the intrinsic factor vitamin B12 complex in the intestinal lumen. The lesion appears to be one of the mucosal cell receptors or of the cells themselves, possibly caused by bacterial toxins."}
{"id": "PMID:3461", "title": "[Experimental testing of a new gastrotherapeutic agent].", "content": "A new gastrotherapeutical preparation, AcT 72, has been evaluated. This preparation contains the anticholinergic drug propantheline bromide, the psychotherapeutical agent perazine, and antacids. In two different series of tests it was demonstrated that after a peroral dose of ACT72, gastric motility was significantly reduced when compared with the control situation. Dosages used were in accordance with normal therapeutic doses, and, because of the influence on gastric motility, the duration of action in the stomach was prolonged, thus reducing daily dose requirements. Reduction of stomach motility per se, has therapeutic value in patients with gastric ulcers.", "contents": "[Experimental testing of a new gastrotherapeutic agent]. A new gastrotherapeutical preparation, AcT 72, has been evaluated. This preparation contains the anticholinergic drug propantheline bromide, the psychotherapeutical agent perazine, and antacids. In two different series of tests it was demonstrated that after a peroral dose of ACT72, gastric motility was significantly reduced when compared with the control situation. Dosages used were in accordance with normal therapeutic doses, and, because of the influence on gastric motility, the duration of action in the stomach was prolonged, thus reducing daily dose requirements. Reduction of stomach motility per se, has therapeutic value in patients with gastric ulcers."}
{"id": "PMID:3462", "title": "[The disulfide bridges of the trypsin-kallikrein inhibitor K from snails (Helix pomatia). Thermal inactivation and proteolysis by thermolysin (author's transl)].", "content": "Isoinhibitor K is the main component of the complex mixture of isoinhibitors of broad specificity secreted into the mucus by the Roman snail (Helix pomatia). The disulfide pairing was determined after the amino acid sequence had been elucidated. Two cystine-containing peptides with the disulfide bridges Cys32-Cys53 and Cys32-Cys53 plus Cys7-Cys57 were obtained after thermolytic hydrolysis of the native inhibitor at 80 degrees C and chromatographic separation of the peptides using SE-Sephadex. The Cys16-Cys40 disulfide bridge could be reduced selectively by sodium borohydride with no loss in biological activity. This property and the covalent structure correspond to that of the intracellular inhibitor from bovine organs, which is largely homologous in its amino acid sequence to the secretory inhibitor from the snail. The complete covalent structure of isoinhibitor K will be presented. The snail inhibitor is less stable against proteolytic inactivation by thermolysin and against thermal denaturation at pH 8.0 than the inhibitor from bovine organs (Kunitz inhibitor).", "contents": "[The disulfide bridges of the trypsin-kallikrein inhibitor K from snails (Helix pomatia). Thermal inactivation and proteolysis by thermolysin (author's transl)]. Isoinhibitor K is the main component of the complex mixture of isoinhibitors of broad specificity secreted into the mucus by the Roman snail (Helix pomatia). The disulfide pairing was determined after the amino acid sequence had been elucidated. Two cystine-containing peptides with the disulfide bridges Cys32-Cys53 and Cys32-Cys53 plus Cys7-Cys57 were obtained after thermolytic hydrolysis of the native inhibitor at 80 degrees C and chromatographic separation of the peptides using SE-Sephadex. The Cys16-Cys40 disulfide bridge could be reduced selectively by sodium borohydride with no loss in biological activity. This property and the covalent structure correspond to that of the intracellular inhibitor from bovine organs, which is largely homologous in its amino acid sequence to the secretory inhibitor from the snail. The complete covalent structure of isoinhibitor K will be presented. The snail inhibitor is less stable against proteolytic inactivation by thermolysin and against thermal denaturation at pH 8.0 than the inhibitor from bovine organs (Kunitz inhibitor)."}
{"id": "PMID:3463", "title": "[The inter-alpha-trypsin inhibitor as precursor of the acid-stable proteinase inhibitors in human serum and urine].", "content": "A small amount of antitryptic activity is detectable in the supernatant of deproteinized human serum. Preincubation of serum with trypsin causes an increase in acid-stable antitryptic activity. This rise in activity depends on the inter alpha-trypsin inhibitor concentration. The native inhibitor present in normal sera, and in higher concentrations in sera of patients with nephropathies, and the trypsin-liberated inhibitor show immunological cross reaction with antibodies to the serum inter-alpha-trypsin inhibitor. The two inhibitors differ in molecular weight and electrophoretic mobility. The physiological inhibitor (I-34), with a molecular weight of 34 000 and a high carbohydrate content, can be transformed by trypsin into an inhibitor (I-17) with a molecular weight of 17 000. This inhibitor is identical with the inhibitors liberated by trypsin from serum or from purified inter-alpha-trypsin inhibitor. The acid-stable inhibitor from urine is identical with the physiological serum inhibitor. Analogously, this inhibitor is transformed by trypsin into the inhibitor with a molecular weight of 17 000. We conclude that the inter-alpha-trypsin inhibitor is the precursor of both the physiological and the trypsin-liberated inhibitor. By a mechanism as yet unknown, but most likely a limited proteolysis, the secreted inhibitor is liberated from the high molecular weight precursor. In contrast to the monospecific trypsin-inhibiting precursor, the physiological and artificially liberated inhibitors are trypsin/chymotrypsin/plasmin inhibitors.", "contents": "[The inter-alpha-trypsin inhibitor as precursor of the acid-stable proteinase inhibitors in human serum and urine]. A small amount of antitryptic activity is detectable in the supernatant of deproteinized human serum. Preincubation of serum with trypsin causes an increase in acid-stable antitryptic activity. This rise in activity depends on the inter alpha-trypsin inhibitor concentration. The native inhibitor present in normal sera, and in higher concentrations in sera of patients with nephropathies, and the trypsin-liberated inhibitor show immunological cross reaction with antibodies to the serum inter-alpha-trypsin inhibitor. The two inhibitors differ in molecular weight and electrophoretic mobility. The physiological inhibitor (I-34), with a molecular weight of 34 000 and a high carbohydrate content, can be transformed by trypsin into an inhibitor (I-17) with a molecular weight of 17 000. This inhibitor is identical with the inhibitors liberated by trypsin from serum or from purified inter-alpha-trypsin inhibitor. The acid-stable inhibitor from urine is identical with the physiological serum inhibitor. Analogously, this inhibitor is transformed by trypsin into the inhibitor with a molecular weight of 17 000. We conclude that the inter-alpha-trypsin inhibitor is the precursor of both the physiological and the trypsin-liberated inhibitor. By a mechanism as yet unknown, but most likely a limited proteolysis, the secreted inhibitor is liberated from the high molecular weight precursor. In contrast to the monospecific trypsin-inhibiting precursor, the physiological and artificially liberated inhibitors are trypsin/chymotrypsin/plasmin inhibitors."}
{"id": "PMID:3464", "title": "Plant microbody proteins, I. Purification and characterization of catalase from leaves of lens culinaris.", "content": "1) Catalase from green leaves of Lens culinaris (lentils) was investigated with respect to isoenzyme patterns. In contrast to other plants, which have been reported to contain multiple forms of catalase, only one form of this enzyme was revealed when crude extracts were subjected to starch gel electrophoresis or to polyacrylamide disc-gel electrophoresis. Furthermore, catalases from leaves, stems and cotyledons were electrophoretically identical. 2) The leaf enzyme has been purified by conventional methods to apparent homogeneity. It has a molecular weight of 225 000 (ultracentrifuge) and is composed of four identical subunits of molecular weight 54 000 (sodium dodecylsulphate gel electrophoresis). The ratio A280/A405 of the pure enzyme was found to be 1.5. The isoelectric point is at pH 5.5. The enzyme, very labile at pH-values below 7.0, is stable in Tris chloride and potassium phosphate buffers between pH 7.5 and 9.5. It is slowly inactivated by 1mM dithiothreitol and is rapidly inactivated by 1mM mercaptoethanol. 3) The catalase was shown to be the major protein component of the peroxisomal matrix. It could not be detected at the membranes of the leaf peroxisomes.", "contents": "Plant microbody proteins, I. Purification and characterization of catalase from leaves of lens culinaris. 1) Catalase from green leaves of Lens culinaris (lentils) was investigated with respect to isoenzyme patterns. In contrast to other plants, which have been reported to contain multiple forms of catalase, only one form of this enzyme was revealed when crude extracts were subjected to starch gel electrophoresis or to polyacrylamide disc-gel electrophoresis. Furthermore, catalases from leaves, stems and cotyledons were electrophoretically identical. 2) The leaf enzyme has been purified by conventional methods to apparent homogeneity. It has a molecular weight of 225 000 (ultracentrifuge) and is composed of four identical subunits of molecular weight 54 000 (sodium dodecylsulphate gel electrophoresis). The ratio A280/A405 of the pure enzyme was found to be 1.5. The isoelectric point is at pH 5.5. The enzyme, very labile at pH-values below 7.0, is stable in Tris chloride and potassium phosphate buffers between pH 7.5 and 9.5. It is slowly inactivated by 1mM dithiothreitol and is rapidly inactivated by 1mM mercaptoethanol. 3) The catalase was shown to be the major protein component of the peroxisomal matrix. It could not be detected at the membranes of the leaf peroxisomes."}
{"id": "PMID:3465", "title": "The activator of human cerebroside sulphatase. Activating effect on the acidic forms of the sulphatases from invertebrates.", "content": "1) Acidic forms of the sulphatase were partially purified from the following invertebrate species: Tethya aurantium (Porifera), Patella vulgata (mollusca), Maja squinado (Arthropoda), Marthasterias glacialis (Echinodermata) and Microcosmus sulcatus (Tunicata). Enzyme preparations thus obtained cleaved cerebroside sulphates (sulphatides) only in the presence of either specific detergents (e.g. taurodeoxycholate) or an activator protein isolated from human liver. This corresponds to the findings on purified sulphatase A of human origin. 2) At low concentrations, the activating effect was proportional to the amount of activator protein applied; at higher concentrations, proportionality was obtained only in some cases. On a molar basis, less of the activator protein was required to achieve the same activation as taurodeoxycholate. At optimum concentrations of the detergent however, the activation was much higher. 3) The enzyme specificity of the activator and some evolutionary implications are discussed.", "contents": "The activator of human cerebroside sulphatase. Activating effect on the acidic forms of the sulphatases from invertebrates. 1) Acidic forms of the sulphatase were partially purified from the following invertebrate species: Tethya aurantium (Porifera), Patella vulgata (mollusca), Maja squinado (Arthropoda), Marthasterias glacialis (Echinodermata) and Microcosmus sulcatus (Tunicata). Enzyme preparations thus obtained cleaved cerebroside sulphates (sulphatides) only in the presence of either specific detergents (e.g. taurodeoxycholate) or an activator protein isolated from human liver. This corresponds to the findings on purified sulphatase A of human origin. 2) At low concentrations, the activating effect was proportional to the amount of activator protein applied; at higher concentrations, proportionality was obtained only in some cases. On a molar basis, less of the activator protein was required to achieve the same activation as taurodeoxycholate. At optimum concentrations of the detergent however, the activation was much higher. 3) The enzyme specificity of the activator and some evolutionary implications are discussed."}
{"id": "PMID:3466", "title": "Multiple forms of boar acrosin and their relationship to proenzyme activation.", "content": "Further evidence is presented that the acrosomal proteinase acrosin exists as a zymogen precursor in freshly ejaculated boar spermatozoa. Autoactivation of proacrosin to acrosin takes place optimally at slightly alkaline pH and in the presence of calcium ions. Activation is considerably accelerated by catalytic amounts of trypsin or highly purified acrosin. A significant acceleration of the activation is also achieved by porcine pancreatic and urinary kallikrein, whereas chymotrypsin, plasmin, thrombin or urokinase showed no effect. Activation can be inhibited by p-amino-benzamidine and p-nitrophenyl p'-guanidino-benzoate. Electrophoretic analysis at different stages of activation revealed that during this process various molecular forms of acrosin are produced, apparently by limited proteolysis.", "contents": "Multiple forms of boar acrosin and their relationship to proenzyme activation. Further evidence is presented that the acrosomal proteinase acrosin exists as a zymogen precursor in freshly ejaculated boar spermatozoa. Autoactivation of proacrosin to acrosin takes place optimally at slightly alkaline pH and in the presence of calcium ions. Activation is considerably accelerated by catalytic amounts of trypsin or highly purified acrosin. A significant acceleration of the activation is also achieved by porcine pancreatic and urinary kallikrein, whereas chymotrypsin, plasmin, thrombin or urokinase showed no effect. Activation can be inhibited by p-amino-benzamidine and p-nitrophenyl p'-guanidino-benzoate. Electrophoretic analysis at different stages of activation revealed that during this process various molecular forms of acrosin are produced, apparently by limited proteolysis."}
{"id": "PMID:3471", "title": "[Conditions for the efficacy of nutritional therapy].", "content": "This is to discuss regulatory mechanisms which enable the organism to respond optimally to special nutritive conditions. Those regulatory mechanisms are often in disorder with patients who need nutritive therapy. However, normal functions of the body are required for nutrition. Disarrangements in microcirculation, oxygen supply, water and electrolyte metabolism and acid-base metabolism are described and the way they will influence nutrition therapy. Furthermore, we try to describe special conditions of metabolism in stress and its influence to efficiency of nutritive therapy.", "contents": "[Conditions for the efficacy of nutritional therapy]. This is to discuss regulatory mechanisms which enable the organism to respond optimally to special nutritive conditions. Those regulatory mechanisms are often in disorder with patients who need nutritive therapy. However, normal functions of the body are required for nutrition. Disarrangements in microcirculation, oxygen supply, water and electrolyte metabolism and acid-base metabolism are described and the way they will influence nutrition therapy. Furthermore, we try to describe special conditions of metabolism in stress and its influence to efficiency of nutritive therapy."}
{"id": "PMID:3472", "title": "[Clinical testing of bronchospasmolytics in combined alternating test schedules].", "content": "NAB 365, a new beta2-adrenergic bronchodilator was tested in oral doses of 0.01, 0.02, 0.03 and 0.04 mg. An acute trial was carried out in outpatients suffering from chronic obstructive airways disease. Airway resistance was measured by bodyplethysmography. For doses from 0.02 to 0.04 mg NAB 365 a quick, dose related and statistically significant bronchodliation without remarkable side effects could be found. The application of Fenoterol and Sch 1000 (ipratropiumbromide) by a metered dose inhaler was followed by a further and finally equal bronchodilation. To avoid adrenergic side effects the combination of NAB 365 with Sch 1000 should be preferred to the combination of NAB 365 with Fenoterol.", "contents": "[Clinical testing of bronchospasmolytics in combined alternating test schedules]. NAB 365, a new beta2-adrenergic bronchodilator was tested in oral doses of 0.01, 0.02, 0.03 and 0.04 mg. An acute trial was carried out in outpatients suffering from chronic obstructive airways disease. Airway resistance was measured by bodyplethysmography. For doses from 0.02 to 0.04 mg NAB 365 a quick, dose related and statistically significant bronchodliation without remarkable side effects could be found. The application of Fenoterol and Sch 1000 (ipratropiumbromide) by a metered dose inhaler was followed by a further and finally equal bronchodilation. To avoid adrenergic side effects the combination of NAB 365 with Sch 1000 should be preferred to the combination of NAB 365 with Fenoterol."}
{"id": "PMID:3473", "title": "The first transplantation of a Fallopian tube of frozen material in woman.", "content": "There is an ever-present possibility that the children or husband of a sterilized woman may die. In the latter case, and after remarriage, she and her new husband may want children of their own, which presents difficulties, as the low success rate of reconstructive surgery in the sterilised woman is well known. A case history is presented of the first sterilized woman to undergo Fallopian tube transplantation.", "contents": "The first transplantation of a Fallopian tube of frozen material in woman. There is an ever-present possibility that the children or husband of a sterilized woman may die. In the latter case, and after remarriage, she and her new husband may want children of their own, which presents difficulties, as the low success rate of reconstructive surgery in the sterilised woman is well known. A case history is presented of the first sterilized woman to undergo Fallopian tube transplantation."}
{"id": "PMID:3474", "title": "An objective method for evaluating Angus and Hereford sperm motility.", "content": "Angus and Hereford sperm motility was evaluated by an objective spectrophotometric procedure and by a conventional subjective ranking system. Semen was collected by electroejaculation and divided so that one group contained 6 Angus samples and one group contained 12 Hereford samples. Objective procedures indicated that Angus sperm was twice motile as Hereford sperm in 2.9% sodium citrate. This objective procedure depends on the orientation of sperm in a flowing liquid and then spectrophotometrically measuring the sperm's ability to return to randomness when the flow is stopped. During preparation for freezing with liquid nitrogen, microscopic subjective ranking of sperm motility was carried out. Three conditions were studied subjectively: (I) arrival at the laboratory, (II) pre-freeze, and (III) thawed samples. No significant differences in subjective evaluation of sperm motility was found between conditions or breeds. Preliminary results indicate that this objective procedure can distinguish between the sperm motility in 2.9% sodium citrate from two breeds of cattle. Use of this objective procedure for studies relating to fertilization and artificial insemination is evident and there is no theoretical reason why the procedure can not be used with other species.", "contents": "An objective method for evaluating Angus and Hereford sperm motility. Angus and Hereford sperm motility was evaluated by an objective spectrophotometric procedure and by a conventional subjective ranking system. Semen was collected by electroejaculation and divided so that one group contained 6 Angus samples and one group contained 12 Hereford samples. Objective procedures indicated that Angus sperm was twice motile as Hereford sperm in 2.9% sodium citrate. This objective procedure depends on the orientation of sperm in a flowing liquid and then spectrophotometrically measuring the sperm's ability to return to randomness when the flow is stopped. During preparation for freezing with liquid nitrogen, microscopic subjective ranking of sperm motility was carried out. Three conditions were studied subjectively: (I) arrival at the laboratory, (II) pre-freeze, and (III) thawed samples. No significant differences in subjective evaluation of sperm motility was found between conditions or breeds. Preliminary results indicate that this objective procedure can distinguish between the sperm motility in 2.9% sodium citrate from two breeds of cattle. Use of this objective procedure for studies relating to fertilization and artificial insemination is evident and there is no theoretical reason why the procedure can not be used with other species."}
{"id": "PMID:3475", "title": "Sperm antibodies in men from infertile couples. Analysis of sperm agglutinins and immunofluorescent antibodies in 657 men.", "content": "Sera from 657 men from infertile couples were tested for sperm agglutinins and spermatozoal antibodies detectable by the indirect immunofluorescense technique (IFT), and the results were correlated to the clinical examinations of the couples. Sperm agglutinins were found in 6.7%. Spontaneous agglutination of the ejaculated spermatozoa was observed only among these men, most commonly among those with high serum titres. IF-antibodies against the four spermatozoal antigens located beneath the cell membrane occurred in 15.2% of the patients. Antibodies against the front part of the acrosome and the postnuclear cap were mainly IgM. Antibodies against the equatorial segment of the acrosome were predominantly IgG and in a few cases IgA, whereas straining of the main tail piece was caused by IgG antibodies. Considering the clinical fertility status of the couples, sperm agglutinins in high titres (greater than or equal to 10) against the equatorial segment and the main tail piece of the spermatozoa were found significantly more often among men from couples with unexplained infertility than among clinically normal men from couples where the findings in the women could be assumed to cause infertility. These results support the view that sperm agglutinins can cause infertility, whereas the significance of the IF-antibodies is still unclarified as, in some cases, these can be found even in high titres in men with proven fertility. The possible mechanism of autosensitization were evaluated by means of an anamnestic study.", "contents": "Sperm antibodies in men from infertile couples. Analysis of sperm agglutinins and immunofluorescent antibodies in 657 men. Sera from 657 men from infertile couples were tested for sperm agglutinins and spermatozoal antibodies detectable by the indirect immunofluorescense technique (IFT), and the results were correlated to the clinical examinations of the couples. Sperm agglutinins were found in 6.7%. Spontaneous agglutination of the ejaculated spermatozoa was observed only among these men, most commonly among those with high serum titres. IF-antibodies against the four spermatozoal antigens located beneath the cell membrane occurred in 15.2% of the patients. Antibodies against the front part of the acrosome and the postnuclear cap were mainly IgM. Antibodies against the equatorial segment of the acrosome were predominantly IgG and in a few cases IgA, whereas straining of the main tail piece was caused by IgG antibodies. Considering the clinical fertility status of the couples, sperm agglutinins in high titres (greater than or equal to 10) against the equatorial segment and the main tail piece of the spermatozoa were found significantly more often among men from couples with unexplained infertility than among clinically normal men from couples where the findings in the women could be assumed to cause infertility. These results support the view that sperm agglutinins can cause infertility, whereas the significance of the IF-antibodies is still unclarified as, in some cases, these can be found even in high titres in men with proven fertility. The possible mechanism of autosensitization were evaluated by means of an anamnestic study."}
{"id": "PMID:3476", "title": "The value of the basal temperature chart in the management of infertility.", "content": "The basal temperature chart (BTC) has been used as a means of screening the ovarian function of infertile patients and for monitoring their response to ovarian stimulation. During three years in a busy infertility clinic, specifically designated for cases of functional infertility, 491 patients were seen and 96 per cent of them kept valid basal temperature charts. The use of the BTC enabled therapy to be instituted early on in the course of investigations in those cases of infertility in which there was an endocrine factor. There were 420 patients in this category; of those who received treatment a high percentage became pregnant in contrast to those who were being observed. It is recommended that the BTC should be used early and more frequently in the management of cases of infertility, since it has been shown to serve as an inexpensive and convenient parameter of ovarian function.", "contents": "The value of the basal temperature chart in the management of infertility. The basal temperature chart (BTC) has been used as a means of screening the ovarian function of infertile patients and for monitoring their response to ovarian stimulation. During three years in a busy infertility clinic, specifically designated for cases of functional infertility, 491 patients were seen and 96 per cent of them kept valid basal temperature charts. The use of the BTC enabled therapy to be instituted early on in the course of investigations in those cases of infertility in which there was an endocrine factor. There were 420 patients in this category; of those who received treatment a high percentage became pregnant in contrast to those who were being observed. It is recommended that the BTC should be used early and more frequently in the management of cases of infertility, since it has been shown to serve as an inexpensive and convenient parameter of ovarian function."}
{"id": "PMID:3477", "title": "Absorption activity of the blood group substances in various fractions of split ejaculates from man.", "content": "Antigens of the ABO system have been determined in the various fractions of split ejaculates from three A and two O (H) men who were secretors. The activity of the antigen was determined by a hemagglutination inhibition test. Within a split ejaculate the various fractions contained almost the same antigen activity, indicating that the antigens were secreted from all the glands contributing to the seminal plasma.", "contents": "Absorption activity of the blood group substances in various fractions of split ejaculates from man. Antigens of the ABO system have been determined in the various fractions of split ejaculates from three A and two O (H) men who were secretors. The activity of the antigen was determined by a hemagglutination inhibition test. Within a split ejaculate the various fractions contained almost the same antigen activity, indicating that the antigens were secreted from all the glands contributing to the seminal plasma."}
{"id": "PMID:3478", "title": "The polycystic ovary. I. Estradiol/testosterone ratio and the use of antiestrogens.", "content": "Several treatments have been used to induce ovulation in the polycystic ovary. In the following study, estradiol and testosterone plasma concentration were measured and evaluated in 18 women with polycystic ovaries, as one of the factors involved in the antiestrogenic response to Clomiphene Citrate. An estrogen plasma concentration baseline of 50 pg/ml is proposed in order to obtain the antiestrogenic effects. Nevertheless, induction of ovulation was achieved when the estradiol/testosterone ratio was 0.09 or higher (P less than 0.001).", "contents": "The polycystic ovary. I. Estradiol/testosterone ratio and the use of antiestrogens. Several treatments have been used to induce ovulation in the polycystic ovary. In the following study, estradiol and testosterone plasma concentration were measured and evaluated in 18 women with polycystic ovaries, as one of the factors involved in the antiestrogenic response to Clomiphene Citrate. An estrogen plasma concentration baseline of 50 pg/ml is proposed in order to obtain the antiestrogenic effects. Nevertheless, induction of ovulation was achieved when the estradiol/testosterone ratio was 0.09 or higher (P less than 0.001)."}
{"id": "PMID:3479", "title": "The polycystic ovary. II. Progesterone plasma levels after the use of antiestrogens.", "content": "In the present study, the changes observed in the length of the cycle, basal body temperatures, endometrial histology and plasma progesterone in a group of 18 patients with polycystic ovaries, treated with Clomiphene Citrate, is reported. Two distinctive responses were observed depending on the estradiol/testosterone mean concentration found. Regardless of the induction of ovulation, a clear change in the length of the cycle was observed. Progesterone concentration of 2.1-2.9 ng/ml gave a definite rise in BBT, but no endometrial secretory changes were found in parallel with that concentration. Progesterone concentration above 6.1 ng/ml did induce secretory changes in the endometrium.", "contents": "The polycystic ovary. II. Progesterone plasma levels after the use of antiestrogens. In the present study, the changes observed in the length of the cycle, basal body temperatures, endometrial histology and plasma progesterone in a group of 18 patients with polycystic ovaries, treated with Clomiphene Citrate, is reported. Two distinctive responses were observed depending on the estradiol/testosterone mean concentration found. Regardless of the induction of ovulation, a clear change in the length of the cycle was observed. Progesterone concentration of 2.1-2.9 ng/ml gave a definite rise in BBT, but no endometrial secretory changes were found in parallel with that concentration. Progesterone concentration above 6.1 ng/ml did induce secretory changes in the endometrium."}
{"id": "PMID:3480", "title": "Offspring of subfertile parents. A preliminary survey.", "content": "This preliminary survey reports findings among offspring of subfertile parents. Combining neonatal death, low birth weight and major anomalies, 11 of 60 livebirths (18%) were affected, indicating that subfertility adversely influences neonatal morbidity and mortality. Information was available for 49 of 56 children and there were none with developmental delay nor was there an increase in malformations or minor behavioral or learning disorders. Although numbers are small, these observations suggest that children of subfertile parents who survive the neonatal period do not differ from the normal population.", "contents": "Offspring of subfertile parents. A preliminary survey. This preliminary survey reports findings among offspring of subfertile parents. Combining neonatal death, low birth weight and major anomalies, 11 of 60 livebirths (18%) were affected, indicating that subfertility adversely influences neonatal morbidity and mortality. Information was available for 49 of 56 children and there were none with developmental delay nor was there an increase in malformations or minor behavioral or learning disorders. Although numbers are small, these observations suggest that children of subfertile parents who survive the neonatal period do not differ from the normal population."}
{"id": "PMID:3481", "title": "Increased fibrinolytic activity in the endometrium of patients using copper-iud (gravigard).", "content": "The use of an IUD often causes an increase in the menstrual blood loss, and this is the most common reason for removing the device. The fibrinolytic activity of the endometrium was studied histochemically in 15 women before and after the use of copper-IUD for 2-5 as well as for 8-12 months. The fibrinolytic activity in the endometrium was found to be increased at both examinations. This increase is probably a contributory cause of the menorrhagia in patients with IUD. No significant difference in fibrinolytic activity was found between the two examinations after insertion of the IUD, which thus suggests that the increase in endometrial fibrinolytic activity was steady.", "contents": "Increased fibrinolytic activity in the endometrium of patients using copper-iud (gravigard). The use of an IUD often causes an increase in the menstrual blood loss, and this is the most common reason for removing the device. The fibrinolytic activity of the endometrium was studied histochemically in 15 women before and after the use of copper-IUD for 2-5 as well as for 8-12 months. The fibrinolytic activity in the endometrium was found to be increased at both examinations. This increase is probably a contributory cause of the menorrhagia in patients with IUD. No significant difference in fibrinolytic activity was found between the two examinations after insertion of the IUD, which thus suggests that the increase in endometrial fibrinolytic activity was steady."}
{"id": "PMID:3482", "title": "Effects of aminophylline, imidazole and indomethacin on spontaneous and prostaglandin induced ovarian contractions in vitro.", "content": "Imidazole, acetylcholine, phenylephrine prostaglandin F2alpha, and methyl prostaglandin F2alpha increased the contractility of guinea pig and human ovaries in vitro. This effect was suppressed by aminophylline. Indomethacin inhibited ovarian contractions. The inhibitory effect of indomethacin was reversed by prostaglandin F2alpha or by its methyl derivative. Prostaglandin E2 decreased the amplitude and frequency of the spontaneous and prostaglandin F2alpha induced contractions of guinea pig ovaries in vitro. The study shows that compounds which interfere with cyclic AMP and prostaglandin metabolism affect ovarian contractility in vitro.", "contents": "Effects of aminophylline, imidazole and indomethacin on spontaneous and prostaglandin induced ovarian contractions in vitro. Imidazole, acetylcholine, phenylephrine prostaglandin F2alpha, and methyl prostaglandin F2alpha increased the contractility of guinea pig and human ovaries in vitro. This effect was suppressed by aminophylline. Indomethacin inhibited ovarian contractions. The inhibitory effect of indomethacin was reversed by prostaglandin F2alpha or by its methyl derivative. Prostaglandin E2 decreased the amplitude and frequency of the spontaneous and prostaglandin F2alpha induced contractions of guinea pig ovaries in vitro. The study shows that compounds which interfere with cyclic AMP and prostaglandin metabolism affect ovarian contractility in vitro."}
{"id": "PMID:3483", "title": "Effect of low doses of alpha-chlorohydrin on fertility and semen characteristics and binding of the drug of spermatozoa in swine.", "content": "Daily feeding of 1 mg of alpha-chlorohydrin per kg body weight to boars prevented fertility completely when the ejaculate was used for insemination. The semen charactreated than in untreated boars, but the sperm morphology was otherwise normal. In vitro addition of 5 mg/epididymal contents from the treated boars revealed normal Na+, K+ and glycerylphosphorylcholine concentrations. The movement of sperm cytoplasmic droplets was completed on all spermatozoa more distally in treated than in untreated boars, but the sperm morphology was otherwise normal. In vitro addition of 5 mg/100 ml of alpha-chlorohydrin to ejaculate boar semen completely inhibited and 2.5 mg/100 ml decreased fertility. Removal of the alpha-chlorohydrin prior to insemination partially restored fertility. 14C-alpha-chlorohydrin was shown to be more firmly bound to boar spermatozoa than 14C-carboxyinulin and could not be removed from the spermatozoa with 3 washings. The contraceptive mechanism of the drug is suggested to be alkylation of the sperm membrane by free alpha-chlorohydrin in the epididymis.", "contents": "Effect of low doses of alpha-chlorohydrin on fertility and semen characteristics and binding of the drug of spermatozoa in swine. Daily feeding of 1 mg of alpha-chlorohydrin per kg body weight to boars prevented fertility completely when the ejaculate was used for insemination. The semen charactreated than in untreated boars, but the sperm morphology was otherwise normal. In vitro addition of 5 mg/epididymal contents from the treated boars revealed normal Na+, K+ and glycerylphosphorylcholine concentrations. The movement of sperm cytoplasmic droplets was completed on all spermatozoa more distally in treated than in untreated boars, but the sperm morphology was otherwise normal. In vitro addition of 5 mg/100 ml of alpha-chlorohydrin to ejaculate boar semen completely inhibited and 2.5 mg/100 ml decreased fertility. Removal of the alpha-chlorohydrin prior to insemination partially restored fertility. 14C-alpha-chlorohydrin was shown to be more firmly bound to boar spermatozoa than 14C-carboxyinulin and could not be removed from the spermatozoa with 3 washings. The contraceptive mechanism of the drug is suggested to be alkylation of the sperm membrane by free alpha-chlorohydrin in the epididymis."}
{"id": "PMID:3484", "title": "Active transport system in human spermatozoa.", "content": "The presence of potassium influx into human spermatozoa was investigated through the use of radioactive K42 and Rb86. A gradient of potassium and sodium has been found between the spermatozoal midpiece-tail region and seminal plasma. The influx of potassium seemed to correlate with spermatozoal motility.", "contents": "Active transport system in human spermatozoa. The presence of potassium influx into human spermatozoa was investigated through the use of radioactive K42 and Rb86. A gradient of potassium and sodium has been found between the spermatozoal midpiece-tail region and seminal plasma. The influx of potassium seemed to correlate with spermatozoal motility."}
{"id": "PMID:3485", "title": "Sperm antibodies in serum and seminal plasma.", "content": "The relation between sperm antibodies (agglutinins and IF-antibodies) in serum and seminal plasma was studied in three selected groups of male partners in infertile couples with respect to specificity, concentrations and immunoglobulin classes. Agglutinins were found in seminal plasma only when they were also present in serum, but there was no strict correlation between the titres in seminal plasma and serum although serum titres were always the higher ones. However, in cases with tail-to-tail agglutinins a difference of more than 2 fourfold steps between the titres was never found; spontaneous agglutination in the ejaculate generally occurred when the seminal plasma titre was 64 or more, and in 6 patients with high seminal plasma titres IgA was detected in the midpiece region of ejaculated spermatozoa. In contrast, head-to-head agglutinins were found in seminal plasma in only one of 3 patients with these agglutinins in serum, and only in a low titre. Absorption of IgG of IgG with protein-A-producing Staphylococcus aureus showed that tail-to-tail agglutinins in serum were IgG antibodies, whereas they could be characterized as \"non-IgA-in seminal plasma, suggesting a local production of these antibodies. IF-antibodies were rarely found in seminal plasma and seemed to be of little significance in relation to infertility in men.", "contents": "Sperm antibodies in serum and seminal plasma. The relation between sperm antibodies (agglutinins and IF-antibodies) in serum and seminal plasma was studied in three selected groups of male partners in infertile couples with respect to specificity, concentrations and immunoglobulin classes. Agglutinins were found in seminal plasma only when they were also present in serum, but there was no strict correlation between the titres in seminal plasma and serum although serum titres were always the higher ones. However, in cases with tail-to-tail agglutinins a difference of more than 2 fourfold steps between the titres was never found; spontaneous agglutination in the ejaculate generally occurred when the seminal plasma titre was 64 or more, and in 6 patients with high seminal plasma titres IgA was detected in the midpiece region of ejaculated spermatozoa. In contrast, head-to-head agglutinins were found in seminal plasma in only one of 3 patients with these agglutinins in serum, and only in a low titre. Absorption of IgG of IgG with protein-A-producing Staphylococcus aureus showed that tail-to-tail agglutinins in serum were IgG antibodies, whereas they could be characterized as \"non-IgA-in seminal plasma, suggesting a local production of these antibodies. IF-antibodies were rarely found in seminal plasma and seemed to be of little significance in relation to infertility in men."}
{"id": "PMID:3489", "title": "[Clinical and experimental observations on idiopathic urticaria due to the contact with heat].", "content": "This study describes the probably eleventh case, mentioned in literature, of acquired heat contact uticaria in an otherwise healthy young woman. With regard to true contact induction heat contact urticaria clearly differs from the more common cholinergic uticaria. On the other hand, heat contact urticaria is completely analogous to cold uticaria because of the exposure area, reversible blocking by unphysiological prolonged heating of the skin, sensitivity to antihistamines and resistance to corticosteroids. In this case, whealing of the skin occurred on exposure to heating of 39 degrees C for 5 min. With a temperature of 44-46 degrees C, The shortest time for wheal induction was 3-5 sec. At 70 degrees C, the shortest time for maximal reaction was only a split second. An \"optimal temperature\" for wheal induction could not be determined. Local anaesthesia with 2% Xylocain caused a considerable blocking of wheals. Histamine and cholinergic drugs showed normal skin reactions after intradermal injection. Antihistamines administered parenterally or perorally were highly effective. Corticosteroids, however, given systemically in high doses proved to be ineffective. During our observations, a spontaneous remission appeared with a clinical symptom-free state; on unphysiological high temperature stimulus, however, contact uticaria could still be demonstrated. The pathogenetic uniformity of sporadic heat contact urticaria and problems of therapeutical controls are discussed.", "contents": "[Clinical and experimental observations on idiopathic urticaria due to the contact with heat]. This study describes the probably eleventh case, mentioned in literature, of acquired heat contact uticaria in an otherwise healthy young woman. With regard to true contact induction heat contact urticaria clearly differs from the more common cholinergic uticaria. On the other hand, heat contact urticaria is completely analogous to cold uticaria because of the exposure area, reversible blocking by unphysiological prolonged heating of the skin, sensitivity to antihistamines and resistance to corticosteroids. In this case, whealing of the skin occurred on exposure to heating of 39 degrees C for 5 min. With a temperature of 44-46 degrees C, The shortest time for wheal induction was 3-5 sec. At 70 degrees C, the shortest time for maximal reaction was only a split second. An \"optimal temperature\" for wheal induction could not be determined. Local anaesthesia with 2% Xylocain caused a considerable blocking of wheals. Histamine and cholinergic drugs showed normal skin reactions after intradermal injection. Antihistamines administered parenterally or perorally were highly effective. Corticosteroids, however, given systemically in high doses proved to be ineffective. During our observations, a spontaneous remission appeared with a clinical symptom-free state; on unphysiological high temperature stimulus, however, contact uticaria could still be demonstrated. The pathogenetic uniformity of sporadic heat contact urticaria and problems of therapeutical controls are discussed."}
{"id": "PMID:3487", "title": "Fluorescence polarization studies on the binding between glutamate dehydrogenase and cytoplasmic aspartate aminotransferase.", "content": "Polarization of fluorescence measurements on aspartate aminotransferase (from pig heart cytosol) labeled with fluorescein isothiocyanate have been used to detect the formation of a soluble complex of this protein wich glutamate dehydrogenase from bovine liver. The binding of the labeled transaminase to dehydrogenase is detectable at catalytic concentrations of the enzymes.", "contents": "Fluorescence polarization studies on the binding between glutamate dehydrogenase and cytoplasmic aspartate aminotransferase. Polarization of fluorescence measurements on aspartate aminotransferase (from pig heart cytosol) labeled with fluorescein isothiocyanate have been used to detect the formation of a soluble complex of this protein wich glutamate dehydrogenase from bovine liver. The binding of the labeled transaminase to dehydrogenase is detectable at catalytic concentrations of the enzymes."}
{"id": "PMID:3490", "title": "Lubrication and cartilage.", "content": "Mechanisms of lubrication of human synovial joints have been analysed in terms of the operating conditions of the joint, the synovial fluid and articular cartilage. In the hip and knee during a walking cycle the load may rise up to four times body weight. In the knee on dropping one metre the load may go up to 25 time body weight. The elastic modulus of cartilage is similar to that of the synthetic rubber of a car tyre. The cartilage surface is rough and in elderly specimens the centre line average is 2-75 mum. The friction force generated in reciprocating tests shows that both cartilage and synovial fluid are important in lubrication. The viscosity-shear rate relationships of normal synovial fluid show that it is non-Newtonian. Osteoarthrosic fluid is less so and rheumatoid fluid is more nearly Newtonian. Experiments with hip joints in a pendulum machine show that fluid film lubrication obtains at some phases of joint action. Boundary lubrication prevails under certain conditions and has been examined with a reciprocating friction machine. Digestion of hyaluronate does not alter the boundary lubrication, but trypsin digestion does. Surface active substances (lauryl sulphate and cetyl 3-ammonium bromide) give a lubricating ability similar to that of synovial fluid. The effectiveness of the two substances varies with pH.", "contents": "Lubrication and cartilage. Mechanisms of lubrication of human synovial joints have been analysed in terms of the operating conditions of the joint, the synovial fluid and articular cartilage. In the hip and knee during a walking cycle the load may rise up to four times body weight. In the knee on dropping one metre the load may go up to 25 time body weight. The elastic modulus of cartilage is similar to that of the synthetic rubber of a car tyre. The cartilage surface is rough and in elderly specimens the centre line average is 2-75 mum. The friction force generated in reciprocating tests shows that both cartilage and synovial fluid are important in lubrication. The viscosity-shear rate relationships of normal synovial fluid show that it is non-Newtonian. Osteoarthrosic fluid is less so and rheumatoid fluid is more nearly Newtonian. Experiments with hip joints in a pendulum machine show that fluid film lubrication obtains at some phases of joint action. Boundary lubrication prevails under certain conditions and has been examined with a reciprocating friction machine. Digestion of hyaluronate does not alter the boundary lubrication, but trypsin digestion does. Surface active substances (lauryl sulphate and cetyl 3-ammonium bromide) give a lubricating ability similar to that of synovial fluid. The effectiveness of the two substances varies with pH."}
{"id": "PMID:3491", "title": "Urea transport-defective strains of Saccharomyces cerevisiae.", "content": "Experiments characterizing the urea active transport system in Saccharomyces cerevisiae indicate that (i) formamide and acetamide are strong competitive inhibitors of urea accumulation, (ii) uptake is maximal at pH 3.3 and is 80% inhibited at pH 6.0, and (iii) adenosine 5'-triphosphate generated by glycolysis in conjunction with formation of an ion gradient is likely the driving force behind urea transport. Mutant strains were isolated that are unable to accumulate urea at external concentrations of 0.25 mM. These strains also exhibit a depressed growth rate on 10 mM urea, indicating existence of a relationship between the active transport and facilitated diffusion modes of urea uptake.", "contents": "Urea transport-defective strains of Saccharomyces cerevisiae. Experiments characterizing the urea active transport system in Saccharomyces cerevisiae indicate that (i) formamide and acetamide are strong competitive inhibitors of urea accumulation, (ii) uptake is maximal at pH 3.3 and is 80% inhibited at pH 6.0, and (iii) adenosine 5'-triphosphate generated by glycolysis in conjunction with formation of an ion gradient is likely the driving force behind urea transport. Mutant strains were isolated that are unable to accumulate urea at external concentrations of 0.25 mM. These strains also exhibit a depressed growth rate on 10 mM urea, indicating existence of a relationship between the active transport and facilitated diffusion modes of urea uptake."}
{"id": "PMID:3492", "title": "Physiological factors affecting transformation of Azotobacter vinelandii.", "content": "Cells of Azotobacter vinelandii (ATCC 12837) can be transformed by exogenous deoxyribonucleic acid towards the end of exponential growth. Transformation occurs at very low frequencies when the deoxyribonucleic acid is purified or when the transformation is carried out in liquid medium. Optimal transformation occurs on plates of Burk nitrogen-free glucose medium containing either high phosphate (10 mM) or low calcium (0 to 0.29 mM) content. Higher levels of calcium are inhibitory, whereas magnesium ions are essential for transformation and growth. Extracellular polymer and capsule are increasingly inhibitory to transformation and are most abundant when the calcium content of the medium is high. Transformation is optimal at pH 7.0 to 7.1 and at 30 C, conditions which also coincide with minimal extracellular polymer production. Nonencapsulated strains are excellent transformation recipients. Glycine-induced pleomorphism reduces the transformation frequency and the degree of inhibition is dependent on the phosphate concentration of the medium. Rifampin resistance and shifts from adenine, hypoxanthine, uracil, and nitrogenase auxotrophy to prototrophy can be achieved. Although single marker transfer is always greater than double marker transfer, the data suggest that rifampin resistance is linked to hypoxanthine, adenine and uracil protorophy at intervals of increasing distance. Rifampin resistance did not appear to be linked to nitrogenase.", "contents": "Physiological factors affecting transformation of Azotobacter vinelandii. Cells of Azotobacter vinelandii (ATCC 12837) can be transformed by exogenous deoxyribonucleic acid towards the end of exponential growth. Transformation occurs at very low frequencies when the deoxyribonucleic acid is purified or when the transformation is carried out in liquid medium. Optimal transformation occurs on plates of Burk nitrogen-free glucose medium containing either high phosphate (10 mM) or low calcium (0 to 0.29 mM) content. Higher levels of calcium are inhibitory, whereas magnesium ions are essential for transformation and growth. Extracellular polymer and capsule are increasingly inhibitory to transformation and are most abundant when the calcium content of the medium is high. Transformation is optimal at pH 7.0 to 7.1 and at 30 C, conditions which also coincide with minimal extracellular polymer production. Nonencapsulated strains are excellent transformation recipients. Glycine-induced pleomorphism reduces the transformation frequency and the degree of inhibition is dependent on the phosphate concentration of the medium. Rifampin resistance and shifts from adenine, hypoxanthine, uracil, and nitrogenase auxotrophy to prototrophy can be achieved. Although single marker transfer is always greater than double marker transfer, the data suggest that rifampin resistance is linked to hypoxanthine, adenine and uracil protorophy at intervals of increasing distance. Rifampin resistance did not appear to be linked to nitrogenase."}
{"id": "PMID:3493", "title": "Role of D-tryptophan oxidase in D-tryptophan utilization by Escherichia coli.", "content": "Mutants of Escherichia coli K-12 that require L-tryptophan (trp) are normally unable to utilize D-tryptophan to fulfill their requirement. However, secondary mutations (dadR) that confer this ability can be isolated. In such strains two distinct enzymes are found to be produced at high levels: D-amino acid oxidase (EC 1.4.3.3) and D-tryptophan oxidase. A convenient assay procedure for D-tryptophan oxidase is described. The two enzymes could be distinguished on the basis of their sensitivity to inhibition by L-phenylalanine and L-tyrosine. Strains that were trp dadR could not grow with D-tryptophan in the presence of L-phenylalanine, but further mutations, Fyo, could be isolated that allowed growth under these conditions. Some of them were characterized by further increases in the level of D-tryptophan oxidase activity and a sharp decrease in D-amino acid oxidase. These kinds of Fyo mutations lay in or near the dadR gene. The substrate specificity of the two enzymes toward a large number of compounds was examined. The transamination of aromatic keto acids was investigated. In the wild-type strain only a single enzyme, transaminase A (EC 2.6.1.5), was found, and it was irreversibly activated when subjected to elevated temperatures. The present state of our knowledge on D-amino acid utilization in E. coli is summarized.", "contents": "Role of D-tryptophan oxidase in D-tryptophan utilization by Escherichia coli. Mutants of Escherichia coli K-12 that require L-tryptophan (trp) are normally unable to utilize D-tryptophan to fulfill their requirement. However, secondary mutations (dadR) that confer this ability can be isolated. In such strains two distinct enzymes are found to be produced at high levels: D-amino acid oxidase (EC 1.4.3.3) and D-tryptophan oxidase. A convenient assay procedure for D-tryptophan oxidase is described. The two enzymes could be distinguished on the basis of their sensitivity to inhibition by L-phenylalanine and L-tyrosine. Strains that were trp dadR could not grow with D-tryptophan in the presence of L-phenylalanine, but further mutations, Fyo, could be isolated that allowed growth under these conditions. Some of them were characterized by further increases in the level of D-tryptophan oxidase activity and a sharp decrease in D-amino acid oxidase. These kinds of Fyo mutations lay in or near the dadR gene. The substrate specificity of the two enzymes toward a large number of compounds was examined. The transamination of aromatic keto acids was investigated. In the wild-type strain only a single enzyme, transaminase A (EC 2.6.1.5), was found, and it was irreversibly activated when subjected to elevated temperatures. The present state of our knowledge on D-amino acid utilization in E. coli is summarized."}
{"id": "PMID:3494", "title": "Transduction of chromosomal genes between enteric bacteria by bacteriophage P1.", "content": "We have used P1 transduction to create intergeneric hybrid strains of enteric bacteria by moving the genA and hut genes between Klebsiella aerogenes, Escherichia coli and Salmonella typhimurium. The use of E. coli as the recipient in such transductions permits the construction of episomes and specialized transducing phage containing non-E. coli material. The effect of host restriction modification and deoxyribonucleic acid homology on the frequency of intergeneric transduction of these loci has been examined.", "contents": "Transduction of chromosomal genes between enteric bacteria by bacteriophage P1. We have used P1 transduction to create intergeneric hybrid strains of enteric bacteria by moving the genA and hut genes between Klebsiella aerogenes, Escherichia coli and Salmonella typhimurium. The use of E. coli as the recipient in such transductions permits the construction of episomes and specialized transducing phage containing non-E. coli material. The effect of host restriction modification and deoxyribonucleic acid homology on the frequency of intergeneric transduction of these loci has been examined."}
{"id": "PMID:3495", "title": "Galactoside accumulation by Escherichia coli, driven by a pH gradient.", "content": "Acidification of the external medium results in thiomethylgalactoside accumulation in an energy-depleted adenosine triphosphatase-negative mutant of Escherichia coli.", "contents": "Galactoside accumulation by Escherichia coli, driven by a pH gradient. Acidification of the external medium results in thiomethylgalactoside accumulation in an energy-depleted adenosine triphosphatase-negative mutant of Escherichia coli."}
{"id": "PMID:3496", "title": "Adenosine 5'-monophosphate-stimulated cyanide-insensitive respiration in mitochondria of Moniliella tomentosa.", "content": "Mitochondria of the yeastlike fungus Moniliella tomentosa oxidize reduced nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate, succinate, isocitrate, and lactate. These oxidations are completely inhibited by cyanide or antimycin A in mitochondria isolated from cells grown in the standard medium. On the other hand, the oxidation of all substrates, except lactate, is almost completely insensitive to cyanide or antimycin A in mitochondria from cells grown in the presence of ethidium bromide. In this instance, the oxidation is mainly mediated by an alternate oxidase which can be blocked by salicyl hydroxamic acid. The alternate oxidase can be specifically stimulated by adenosine 5'-monophosphate and this provides a new method for the characterization of the alternate oxidase in mitochondria of M. tomentosa.", "contents": "Adenosine 5'-monophosphate-stimulated cyanide-insensitive respiration in mitochondria of Moniliella tomentosa. Mitochondria of the yeastlike fungus Moniliella tomentosa oxidize reduced nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate, succinate, isocitrate, and lactate. These oxidations are completely inhibited by cyanide or antimycin A in mitochondria isolated from cells grown in the standard medium. On the other hand, the oxidation of all substrates, except lactate, is almost completely insensitive to cyanide or antimycin A in mitochondria from cells grown in the presence of ethidium bromide. In this instance, the oxidation is mainly mediated by an alternate oxidase which can be blocked by salicyl hydroxamic acid. The alternate oxidase can be specifically stimulated by adenosine 5'-monophosphate and this provides a new method for the characterization of the alternate oxidase in mitochondria of M. tomentosa."}
{"id": "PMID:3497", "title": "Sulfate-reducing pathway in Escherichia coli involving bound intermediates.", "content": "Although a sulfate-reducing pathway in Escherichia coli involving free sulfite and sulfide has been suggested, it is shown that, as in Chlorella, a pathway involving bound intermediates is also present. E. coli extracts contained a sulfotransferase that transferred the sulfonyl group from a nucleosidephosphosulfate to an acceptor to form an organic thiosulfate. This enzyme was specific for adenosine 3'-phosphate 5'-phosphosulfate, did not utilize adenine 5'-phosphosulfate, and transferred to a carrier molecule that was identical with thioredoxin in molecular weight and amino acid composition. In the absence of thioredoxin, only very low levels of the transfer of the sulfo group to thiols was observed. As in Chlorella, thiosulfonate reductase activity that reduced glutathione-S-SO3- to bound sulfide could be detected. In E. coli, this enzyme used reduced nicotinamide adenine dinucleotide phosphate and Mg2+, but did not require the addition of ferredoxin or ferredoxin nicotinamide adenine dinucleotide phosphate reductase. Although in Chlorella the thiosulfonate reductase appears to be a different enzyme from the sulfite reductase, the E. coli thiosulfonate reductase and sulfite reductase may be activities of the same enzyme.", "contents": "Sulfate-reducing pathway in Escherichia coli involving bound intermediates. Although a sulfate-reducing pathway in Escherichia coli involving free sulfite and sulfide has been suggested, it is shown that, as in Chlorella, a pathway involving bound intermediates is also present. E. coli extracts contained a sulfotransferase that transferred the sulfonyl group from a nucleosidephosphosulfate to an acceptor to form an organic thiosulfate. This enzyme was specific for adenosine 3'-phosphate 5'-phosphosulfate, did not utilize adenine 5'-phosphosulfate, and transferred to a carrier molecule that was identical with thioredoxin in molecular weight and amino acid composition. In the absence of thioredoxin, only very low levels of the transfer of the sulfo group to thiols was observed. As in Chlorella, thiosulfonate reductase activity that reduced glutathione-S-SO3- to bound sulfide could be detected. In E. coli, this enzyme used reduced nicotinamide adenine dinucleotide phosphate and Mg2+, but did not require the addition of ferredoxin or ferredoxin nicotinamide adenine dinucleotide phosphate reductase. Although in Chlorella the thiosulfonate reductase appears to be a different enzyme from the sulfite reductase, the E. coli thiosulfonate reductase and sulfite reductase may be activities of the same enzyme."}
{"id": "PMID:3498", "title": "An endonuclease from Escherichia coli that introduces single polynucleotide chain scissions in ultraviolet-irradiated DNA.", "content": "An endonuclease that makes single polynucleotide chain scissions in ultraviolet-irradiated DNA has been purified from Escherichia coli. The activity has the following properties: (a) unirradiated DNA is attacked very little if at all; (b) single strand DNA is not attacked, whether irradiated or not; (c) there is no requirement for divalent cations and the activity is not affected by the addition of EDTA; (d) the pH optimum is approximately 7; (e) the activity is inhibited by 1 M NaCl, single strand DNA, transfer RNA and double strand DNA; (f) the sedimentation coefficient, S20,w, is approximately 2.6; (g) it is a basic protein. The enzyme is tentatively named E. coli endonuclease III. The physiological function of the endonuclease has not yet been established.", "contents": "An endonuclease from Escherichia coli that introduces single polynucleotide chain scissions in ultraviolet-irradiated DNA. An endonuclease that makes single polynucleotide chain scissions in ultraviolet-irradiated DNA has been purified from Escherichia coli. The activity has the following properties: (a) unirradiated DNA is attacked very little if at all; (b) single strand DNA is not attacked, whether irradiated or not; (c) there is no requirement for divalent cations and the activity is not affected by the addition of EDTA; (d) the pH optimum is approximately 7; (e) the activity is inhibited by 1 M NaCl, single strand DNA, transfer RNA and double strand DNA; (f) the sedimentation coefficient, S20,w, is approximately 2.6; (g) it is a basic protein. The enzyme is tentatively named E. coli endonuclease III. The physiological function of the endonuclease has not yet been established."}
{"id": "PMID:3499", "title": "Quaternary conformational changes in human hemoglobin studied by laser photolysis of carboxyhemoglobin.", "content": "These experiments indicate that absorbance changes observed at the 425 nm isosbestic point of the Hb and HbCO following laser photolysis of HbCO provide a direct measure of the rates of quaternary conformational changes between rapidly reacting Hb (the immediate product of full photolysis) and slowly reacting normal deoxyhemoglobin. Hb, first observed by Gibson (Gibson, Q.H. (1959) Biochem. J. 71, 293-303), Has been interpreted as deoxyhemoglobin remaining in the liganded quaternary conformation following rapid removal of ligand by a light pulse. In borate buffers between pH 8.4 and 9.6 particularly simple pH-independent results were obtained which allowed the use of a Monod. Wyman, and Changeux model (Monod, J., Wyman, J., and Changeux, J (1965) J. Mol. Biol. 12, 88-118) to fit the data. In this case Hb is taken to be R state deoxyhemoglobin. Partial photolysis experiments at 425 nm show that the rate of the R - T conformational change at 20 degrees decreases by about a factor of 2 for each additional bound ligand. The rate of the ligand-free conformational change is found to be 920 +/- 60s(-1), 6400 +/- 600s(-1), and 15,700 +/- 700(-1) respectively at 3 degrees, 20 degrees, and 30 degrees. The previously uninterpreted effects of flash length and partial photolysis on the CO recombination kinetics can be explained in terms of the present model. Kinetic results obtained below pH 8 are found to be inconsistent with a two-state model. It appears that binding of inositol hexaphosphate produces a new rapidly reacting quaternary conformation of HbCO.", "contents": "Quaternary conformational changes in human hemoglobin studied by laser photolysis of carboxyhemoglobin. These experiments indicate that absorbance changes observed at the 425 nm isosbestic point of the Hb and HbCO following laser photolysis of HbCO provide a direct measure of the rates of quaternary conformational changes between rapidly reacting Hb (the immediate product of full photolysis) and slowly reacting normal deoxyhemoglobin. Hb, first observed by Gibson (Gibson, Q.H. (1959) Biochem. J. 71, 293-303), Has been interpreted as deoxyhemoglobin remaining in the liganded quaternary conformation following rapid removal of ligand by a light pulse. In borate buffers between pH 8.4 and 9.6 particularly simple pH-independent results were obtained which allowed the use of a Monod. Wyman, and Changeux model (Monod, J., Wyman, J., and Changeux, J (1965) J. Mol. Biol. 12, 88-118) to fit the data. In this case Hb is taken to be R state deoxyhemoglobin. Partial photolysis experiments at 425 nm show that the rate of the R - T conformational change at 20 degrees decreases by about a factor of 2 for each additional bound ligand. The rate of the ligand-free conformational change is found to be 920 +/- 60s(-1), 6400 +/- 600s(-1), and 15,700 +/- 700(-1) respectively at 3 degrees, 20 degrees, and 30 degrees. The previously uninterpreted effects of flash length and partial photolysis on the CO recombination kinetics can be explained in terms of the present model. Kinetic results obtained below pH 8 are found to be inconsistent with a two-state model. It appears that binding of inositol hexaphosphate produces a new rapidly reacting quaternary conformation of HbCO."}
{"id": "PMID:3500", "title": "Muscarinic acetylcholine receptor from rat brain. Partial purification and characterization.", "content": "A protein capable of binding atropine and (3H)propylbenzilylcholine mustard was solubilized and purified (200-fold) from rat brain. Pronase and trypsin, but not phospholipases, diminished the binding capacity of the solubilized receptor. The molecular weight of the salt-solubilized receptor as determined by gel filtration in the absence of detergents is 30,000. The purified protein showed specificity of binding toward muscarinic ligands. the high and low affinity dissociation constants of the receptor.atropine complex are 0.3 nM and 0.15 muM. Binding of atropine is pH-dependent with an optimum at 7.1. Ca2+ influences the binding of atropine and maximal binding occurs at 0.5 mM Ca2+. The subcellular distribution of the receptor was also examined.", "contents": "Muscarinic acetylcholine receptor from rat brain. Partial purification and characterization. A protein capable of binding atropine and (3H)propylbenzilylcholine mustard was solubilized and purified (200-fold) from rat brain. Pronase and trypsin, but not phospholipases, diminished the binding capacity of the solubilized receptor. The molecular weight of the salt-solubilized receptor as determined by gel filtration in the absence of detergents is 30,000. The purified protein showed specificity of binding toward muscarinic ligands. the high and low affinity dissociation constants of the receptor.atropine complex are 0.3 nM and 0.15 muM. Binding of atropine is pH-dependent with an optimum at 7.1. Ca2+ influences the binding of atropine and maximal binding occurs at 0.5 mM Ca2+. The subcellular distribution of the receptor was also examined."}
{"id": "PMID:3501", "title": "Quantitative relationships between phosphorylation, electron flow, and internal hydrogen ion concentrations in spinach chloroplasts.", "content": "1. Further evidence that the uptake of [14C]hexylamine, determined by centrifugal filtration of spinach chloroplast thylakoids through silicone fluid layers, gives precise estimations of light-induced H+ concentration gradients (deltapH) is presented. DeltapH was independent of the amount of thylakoids used or of the concentration of hexylamine. Moreover, hexylamine uptake was sensitive to the osmolarity of the suspending medium. 2. Internal H+ concentration ([H+]in) is proportional to the rate of electron flow when light intensity was used to vary these parameters. Proportionality was still observed in the presence of 0.1 and 1.0 muM gramicidin D. When, however, [H+]in and electron flow were varied by increasing the concentration of gramicidin D, at constant light intensity the rate of electron flow was approximately proportional to 1/[H]in. 3. The phosphorylation efficiency (P/e2 ratio) falls with decreasing light intensity or increasing concentrations of the phosphorylation inhibitor, 4'-deoxyphlorizin. The proportionality between the rate of electron flow and [H+]in allows the calculation of the rate of nonphosphorylating (basal) electron flow if [H+]in under phosphorylating conditions is known. The contribution of basal electron flow, a consequence of passive efflux of H+ from the thylakoids, to the overall rate of electron flow increases as the rate of phosphorylation decreases. P/e2 ratios calculated using rates of electron flow from which the basal component has been subtracted are constant. A calculated P/e2 ratio of about 1.3 is obtained. 4. It is shown that the reciprocal of the phosphorylation efficiency should be proportional to 1/[H+]in2 when these parameters are varied using light intensity. This relationship was verified and provided an estimate of the P/e2 at infinite [H+]in. This value was 1.3. These results provide further evidence that a H+ electrochemical gradient serves to couple photophosphorylation to electron flow and that the rate of phosphorylation is proportional to [H+]in3. That is, three H+ are translocated out of thylakoids for each adenosine triphosphate formed.", "contents": "Quantitative relationships between phosphorylation, electron flow, and internal hydrogen ion concentrations in spinach chloroplasts. 1. Further evidence that the uptake of [14C]hexylamine, determined by centrifugal filtration of spinach chloroplast thylakoids through silicone fluid layers, gives precise estimations of light-induced H+ concentration gradients (deltapH) is presented. DeltapH was independent of the amount of thylakoids used or of the concentration of hexylamine. Moreover, hexylamine uptake was sensitive to the osmolarity of the suspending medium. 2. Internal H+ concentration ([H+]in) is proportional to the rate of electron flow when light intensity was used to vary these parameters. Proportionality was still observed in the presence of 0.1 and 1.0 muM gramicidin D. When, however, [H+]in and electron flow were varied by increasing the concentration of gramicidin D, at constant light intensity the rate of electron flow was approximately proportional to 1/[H]in. 3. The phosphorylation efficiency (P/e2 ratio) falls with decreasing light intensity or increasing concentrations of the phosphorylation inhibitor, 4'-deoxyphlorizin. The proportionality between the rate of electron flow and [H+]in allows the calculation of the rate of nonphosphorylating (basal) electron flow if [H+]in under phosphorylating conditions is known. The contribution of basal electron flow, a consequence of passive efflux of H+ from the thylakoids, to the overall rate of electron flow increases as the rate of phosphorylation decreases. P/e2 ratios calculated using rates of electron flow from which the basal component has been subtracted are constant. A calculated P/e2 ratio of about 1.3 is obtained. 4. It is shown that the reciprocal of the phosphorylation efficiency should be proportional to 1/[H+]in2 when these parameters are varied using light intensity. This relationship was verified and provided an estimate of the P/e2 at infinite [H+]in. This value was 1.3. These results provide further evidence that a H+ electrochemical gradient serves to couple photophosphorylation to electron flow and that the rate of phosphorylation is proportional to [H+]in3. That is, three H+ are translocated out of thylakoids for each adenosine triphosphate formed."}
{"id": "PMID:3502", "title": "Kinetic properties of human placental aromatase. Application of an assay measuring 3H2O release from 1beta,2beta-3H-androgens.", "content": "The rapid and sensitive assay of 1beta,2beta-3H-androgen aromatization by measurement of 3H2O release (Thompson, E.A., Jr., and Siiteri, P.K. (1974) J. Biol. Chem. 249, 5364-5372) has been analyzed to determine its applicability to initial rate studies. It was found that aromatization is the sole reaction catalyzed by lyophilized placental microsomes that causes a loss of tritium from position 1 or 2 of androstenedione and testosterone. Tritium is, however, removed from position 2 of the estrogen products, presumably in 2-hydroxylation, but this does not invalidate use of the assay for initial rate measurements; it was therefore used to characterize the catalytic properties of aromatase. Aromatization by the freeze-dried preparation was stimulated by K+, EDTA, and dithiothreitol, and was maximally active at pH 7.5 TO 8.0. With incubation conditions optimized for these factors, the apparent Km for NADPH is approximately 1 muM. The maximum velocity of androstenedione aromatization exceeds that of testosterone, and the affinity of the substrate binding site is higher for the former substrate, the apparent Km values being 0.1 muM and 0.4 muM, respectively. Mutual competition experiments with the androgen substrates showed that each gives simple competitive inhibition of the other's aromatization; furthermore, the apparent Ki values for each are in close agreement with their respective Km values. Androst-1,4,6-triene-3,17-dione competitively inhibits the aromatization of both androstenedione and testosterone, the apparent Ki, in both cases being 0.2 muM. It is concluded that the two androgen substrates are aromatized at a single, identical site.", "contents": "Kinetic properties of human placental aromatase. Application of an assay measuring 3H2O release from 1beta,2beta-3H-androgens. The rapid and sensitive assay of 1beta,2beta-3H-androgen aromatization by measurement of 3H2O release (Thompson, E.A., Jr., and Siiteri, P.K. (1974) J. Biol. Chem. 249, 5364-5372) has been analyzed to determine its applicability to initial rate studies. It was found that aromatization is the sole reaction catalyzed by lyophilized placental microsomes that causes a loss of tritium from position 1 or 2 of androstenedione and testosterone. Tritium is, however, removed from position 2 of the estrogen products, presumably in 2-hydroxylation, but this does not invalidate use of the assay for initial rate measurements; it was therefore used to characterize the catalytic properties of aromatase. Aromatization by the freeze-dried preparation was stimulated by K+, EDTA, and dithiothreitol, and was maximally active at pH 7.5 TO 8.0. With incubation conditions optimized for these factors, the apparent Km for NADPH is approximately 1 muM. The maximum velocity of androstenedione aromatization exceeds that of testosterone, and the affinity of the substrate binding site is higher for the former substrate, the apparent Km values being 0.1 muM and 0.4 muM, respectively. Mutual competition experiments with the androgen substrates showed that each gives simple competitive inhibition of the other's aromatization; furthermore, the apparent Ki values for each are in close agreement with their respective Km values. Androst-1,4,6-triene-3,17-dione competitively inhibits the aromatization of both androstenedione and testosterone, the apparent Ki, in both cases being 0.2 muM. It is concluded that the two androgen substrates are aromatized at a single, identical site."}
{"id": "PMID:3503", "title": "Apparent oxidation-reduction potential of Clostridium acidi-urici ferredoxin. Effect of pH, ionic strength, and amino acid replacements.", "content": "The effects of pH and ionic strength on the midpoint reduction potential (Emp) of Clostridium acidi-urici ferredoxin were determined using hydrogen gas and hydrogenase. The Emp of native ferredoxin at 24-25 degrees in 0.1 M Tris-chloride buffer, pH 7.0, is--0.434 V. In the pH range examined, the Emp becomes approximately 13 mv more negative per each pH unit increase. A plot of the log of ionic strength versus the apparent Emp of ferredoxin in 0.1 M Tris-chloride buffer, pH 7.5, Was linear over the range of 1.0 to 0.01 ionic strength with Emp values of--0.414 and--0.475 V, respectively, at these extremes. This effect is the same with sodium chloride, sodium bromide, or ammonium sulfate. Potassium phosphate buffer caused a similar change, but the absolute values of Emp differed from those obtained in the presence of the other salts. This effect of pH and ionic strength on Emp may be general for clostridial-type (Fe4S4)2-ferredoxins, since the apparent Emp of Clostridium pasteurianum ferredoxin is affected in a similar manner by these two variables. The Emp of this ferredoxin in 0.1 M Tris-chloride buffer pH 7.0, is--0.405 V. Since the NH2-terminal amino acid residue, Ala1, and Tyr2 of C. acidi urici ferredoxin are near an (Fe4S4)2-cluster in the protein, the apparent Emp of derivatives that contained amino acid replacements in these two positions were determined. Under similar conditions, the Emp of most of the 13 derivatives examined, including those of [Leu2]- and[3-NH2-Tyr30]ferredoxin, is approximately the same as that of native ferredoxin. However, the Emp of [His2]ferredoxin is approximately 15 mv more positive, whereas that of [Trp2]ferredoxin is 22 mv more negative than that of native C. acidi-urici ferredoxin. Variations in sodium chloride concentration and pH also affected the apparent Emp of the derivatives. It is suggested that the changes observed in the Emp of C. acidi-urici ferredoxin are caused by protein conformational changes.", "contents": "Apparent oxidation-reduction potential of Clostridium acidi-urici ferredoxin. Effect of pH, ionic strength, and amino acid replacements. The effects of pH and ionic strength on the midpoint reduction potential (Emp) of Clostridium acidi-urici ferredoxin were determined using hydrogen gas and hydrogenase. The Emp of native ferredoxin at 24-25 degrees in 0.1 M Tris-chloride buffer, pH 7.0, is--0.434 V. In the pH range examined, the Emp becomes approximately 13 mv more negative per each pH unit increase. A plot of the log of ionic strength versus the apparent Emp of ferredoxin in 0.1 M Tris-chloride buffer, pH 7.5, Was linear over the range of 1.0 to 0.01 ionic strength with Emp values of--0.414 and--0.475 V, respectively, at these extremes. This effect is the same with sodium chloride, sodium bromide, or ammonium sulfate. Potassium phosphate buffer caused a similar change, but the absolute values of Emp differed from those obtained in the presence of the other salts. This effect of pH and ionic strength on Emp may be general for clostridial-type (Fe4S4)2-ferredoxins, since the apparent Emp of Clostridium pasteurianum ferredoxin is affected in a similar manner by these two variables. The Emp of this ferredoxin in 0.1 M Tris-chloride buffer pH 7.0, is--0.405 V. Since the NH2-terminal amino acid residue, Ala1, and Tyr2 of C. acidi urici ferredoxin are near an (Fe4S4)2-cluster in the protein, the apparent Emp of derivatives that contained amino acid replacements in these two positions were determined. Under similar conditions, the Emp of most of the 13 derivatives examined, including those of [Leu2]- and[3-NH2-Tyr30]ferredoxin, is approximately the same as that of native ferredoxin. However, the Emp of [His2]ferredoxin is approximately 15 mv more positive, whereas that of [Trp2]ferredoxin is 22 mv more negative than that of native C. acidi-urici ferredoxin. Variations in sodium chloride concentration and pH also affected the apparent Emp of the derivatives. It is suggested that the changes observed in the Emp of C. acidi-urici ferredoxin are caused by protein conformational changes."}
{"id": "PMID:3504", "title": "A deoxyribonucleic acid kinase from nuclei of rat liver. Purification and properties.", "content": "A DNA kinase has been partially purified from rat liver nuclei by a procedure which also yields DNA ligase. The kinase uses ATP to phosphorylate specifically the 5'-hydroxyl termini of oligodeoxynucleotides and of single- or double-stranded DNA, yielding 5'-phosphate termini and ADP. The kinase is inactive on RNA, or on oligodeoxynucleotides of chain length less than approximately 10 to 12 residues. The kinase requires a divalent cation (Mg2+, Mn2+, Co2+, Zn2+, Ni2+, or Ca2+) for activity and has an acidic pH optimum. It is inhibited by a variety of nucleotides as well as by very low levels of inorganic and organic sulfate compounds and sulfate analogues. The molecular weight of the kinase is estimated to be 8 times 10(4) from gel filtration.", "contents": "A deoxyribonucleic acid kinase from nuclei of rat liver. Purification and properties. A DNA kinase has been partially purified from rat liver nuclei by a procedure which also yields DNA ligase. The kinase uses ATP to phosphorylate specifically the 5'-hydroxyl termini of oligodeoxynucleotides and of single- or double-stranded DNA, yielding 5'-phosphate termini and ADP. The kinase is inactive on RNA, or on oligodeoxynucleotides of chain length less than approximately 10 to 12 residues. The kinase requires a divalent cation (Mg2+, Mn2+, Co2+, Zn2+, Ni2+, or Ca2+) for activity and has an acidic pH optimum. It is inhibited by a variety of nucleotides as well as by very low levels of inorganic and organic sulfate compounds and sulfate analogues. The molecular weight of the kinase is estimated to be 8 times 10(4) from gel filtration."}
{"id": "PMID:3505", "title": "Hydrogen exchange at the amide group of reduced pyridine nucleotides and the inhibition of that reaction by dehydrogenases.", "content": "Stopped flow ultraviolet spectroscopy has been used to measure the rate of hydrogen exchange with solvent at the amide group of reduced nicotinamide nucleotide coenzymes. Several mechanisms for the exchange reaction are considered in the light of the kinetic data. Complex formation between the coenzyme and any of four dehydrogenases markedly slows the rate of hydrogen exchange. Hydrogen bond formation and/or hydrophobic interactions within these complexes are thought to be the reasons for the decreased rate of exchange.", "contents": "Hydrogen exchange at the amide group of reduced pyridine nucleotides and the inhibition of that reaction by dehydrogenases. Stopped flow ultraviolet spectroscopy has been used to measure the rate of hydrogen exchange with solvent at the amide group of reduced nicotinamide nucleotide coenzymes. Several mechanisms for the exchange reaction are considered in the light of the kinetic data. Complex formation between the coenzyme and any of four dehydrogenases markedly slows the rate of hydrogen exchange. Hydrogen bond formation and/or hydrophobic interactions within these complexes are thought to be the reasons for the decreased rate of exchange."}
{"id": "PMID:3508", "title": "A Dacron wool packed-bed extracorporeal reactor: a kinetic study of immobilized Escherichia coli II L-asparaginase.", "content": "An extracorporeal reactor containing a packed bed of Dacron fibers has been developed. Escherichia coli II L-asparaginase was coupled to the Dacron using gamma-aminopropyltriethoxysilane and glutaraldehyde. The preparation had an activity of 37 IU per gram of Dacron (37 degrees C). The apparent Km was studied as a function of the flow rate. The data indicated that the apparent Km approached the Km of the native enzyme at flow rates of about 300 mg/min. In vivo use of L-asparaginase immobilized on the Dacron indicated effective lowering of plasmatic L-asparagine levels.", "contents": "A Dacron wool packed-bed extracorporeal reactor: a kinetic study of immobilized Escherichia coli II L-asparaginase. An extracorporeal reactor containing a packed bed of Dacron fibers has been developed. Escherichia coli II L-asparaginase was coupled to the Dacron using gamma-aminopropyltriethoxysilane and glutaraldehyde. The preparation had an activity of 37 IU per gram of Dacron (37 degrees C). The apparent Km was studied as a function of the flow rate. The data indicated that the apparent Km approached the Km of the native enzyme at flow rates of about 300 mg/min. In vivo use of L-asparaginase immobilized on the Dacron indicated effective lowering of plasmatic L-asparagine levels."}
{"id": "PMID:3509", "title": "Isolation of intact megakaryocytes from guinea pig femoral marrow. Successful harvest made possible with inhibitions of platelet aggregation; enrichment achieved with a two-step separation technique.", "content": "Methods have been devised to harvest megakaryocytes from guinea pig femoral marrow and to isolate them in high yield. When marrow tissue was disaggregated the megakaryocytes underwent degenerative changes characterized by the loss of cytoplasmic granules and alterations in membrane topography, similar to the changes seen in aggregating platelets. These morphologic changes were interpreted to mean that megakaryocytes possessed functional attributes of platelets. The use of agents which inhibit platelt aggregation (0.38% sodium citrate. 10(-3) M adenosine, and 2 x 10(-3) M theophylline) in a medium free of bivalent cations prevented these changes. This solution resulted in both an excellent morphologic preservation and a significantly increased recovery of megakaryocytes from marrow tissue. A two-step purification of the intact megakaryocytes was carried out on the basis of their low density and large size, with equilibrium density gradient centrifugation followed by velocity sedimentation. This sequence gave approximately a 100-fold enrichment of megakaryocytes, significantly better than that achieved with either method alone. These techniques for harvesting and concentrating megakaryocytes make it possible for the first time to study megakaryocytes in vitro.", "contents": "Isolation of intact megakaryocytes from guinea pig femoral marrow. Successful harvest made possible with inhibitions of platelet aggregation; enrichment achieved with a two-step separation technique. Methods have been devised to harvest megakaryocytes from guinea pig femoral marrow and to isolate them in high yield. When marrow tissue was disaggregated the megakaryocytes underwent degenerative changes characterized by the loss of cytoplasmic granules and alterations in membrane topography, similar to the changes seen in aggregating platelets. These morphologic changes were interpreted to mean that megakaryocytes possessed functional attributes of platelets. The use of agents which inhibit platelt aggregation (0.38% sodium citrate. 10(-3) M adenosine, and 2 x 10(-3) M theophylline) in a medium free of bivalent cations prevented these changes. This solution resulted in both an excellent morphologic preservation and a significantly increased recovery of megakaryocytes from marrow tissue. A two-step purification of the intact megakaryocytes was carried out on the basis of their low density and large size, with equilibrium density gradient centrifugation followed by velocity sedimentation. This sequence gave approximately a 100-fold enrichment of megakaryocytes, significantly better than that achieved with either method alone. These techniques for harvesting and concentrating megakaryocytes make it possible for the first time to study megakaryocytes in vitro."}
{"id": "PMID:3510", "title": "The polymerization of actin. III. Aggregates of nonfilamentous actin and its associated proteins: a storage form of actin.", "content": "When echinoderm sperm are treated with the detergent Triton X-100 at pH 6.4 in 10 mM phosphate buffer, the membranes are solubilized, but the actin which is located in the periacrosomal region remains as a phase-dense cup. These cups can be isolated free from the flagella and chromatin and can be solubilized by increasing the pH to 8.0 and by changing the ionic strength and type of buffer used. Since the actin does not exist in the \"F\" state in unreacted sperm, and since the actin remains as a unit that does not diffuse away, it must be present in the mature sperm in a bound or storage state. The actin is, in fact, associated with a pair of proteins whose mol wt are 250,000 and 230,000. When the isolated cups are digested with trypsin, these high molecular weight proteins are digested, thereby liberating the actin. The actin will polymerize if heavy meromyosin or subfragment 1 is added to a preparation of isolated cups. Evidence is presented that this pair of high molecular weight proteins is similar in molecular weight and properties to erythrocyte spectrin. Attempts at transforming the storage form of actin in the cup into filaments were only moderately successful. The best conditions for filament formation involve incubating the cup in ATP and divalent salts. Careful examination of these cups reveals that the actin polymerized preferentially on either end of oriented filaments that already exist in the cup, indicating that self-nucleation is inefficacious. I conclude that the actin can exist in the storage form by its association with spectrin-like molecules and that the actin in this state polymerizes preferentially onto existing filaments.", "contents": "The polymerization of actin. III. Aggregates of nonfilamentous actin and its associated proteins: a storage form of actin. When echinoderm sperm are treated with the detergent Triton X-100 at pH 6.4 in 10 mM phosphate buffer, the membranes are solubilized, but the actin which is located in the periacrosomal region remains as a phase-dense cup. These cups can be isolated free from the flagella and chromatin and can be solubilized by increasing the pH to 8.0 and by changing the ionic strength and type of buffer used. Since the actin does not exist in the \"F\" state in unreacted sperm, and since the actin remains as a unit that does not diffuse away, it must be present in the mature sperm in a bound or storage state. The actin is, in fact, associated with a pair of proteins whose mol wt are 250,000 and 230,000. When the isolated cups are digested with trypsin, these high molecular weight proteins are digested, thereby liberating the actin. The actin will polymerize if heavy meromyosin or subfragment 1 is added to a preparation of isolated cups. Evidence is presented that this pair of high molecular weight proteins is similar in molecular weight and properties to erythrocyte spectrin. Attempts at transforming the storage form of actin in the cup into filaments were only moderately successful. The best conditions for filament formation involve incubating the cup in ATP and divalent salts. Careful examination of these cups reveals that the actin polymerized preferentially on either end of oriented filaments that already exist in the cup, indicating that self-nucleation is inefficacious. I conclude that the actin can exist in the storage form by its association with spectrin-like molecules and that the actin in this state polymerizes preferentially onto existing filaments."}
{"id": "PMID:3511", "title": "Degradation of abnormal proteins in HeLa cells.", "content": "The experiments show that abnoramal proteins are degraded faster than normal ones in HeLa cells. Among the fragmentary proteins made in the presence of puromycin, those with low molecular weight are least stable. Proteins made after incubation with 5-fluorouracil or in the presence of some amino acid analogues are also unstable. Breakdown of proteins made in the presence or absence of puromycin is nearly unaffected by cycloheximide and is independent of pH between 7 and 8.", "contents": "Degradation of abnormal proteins in HeLa cells. The experiments show that abnoramal proteins are degraded faster than normal ones in HeLa cells. Among the fragmentary proteins made in the presence of puromycin, those with low molecular weight are least stable. Proteins made after incubation with 5-fluorouracil or in the presence of some amino acid analogues are also unstable. Breakdown of proteins made in the presence or absence of puromycin is nearly unaffected by cycloheximide and is independent of pH between 7 and 8."}
{"id": "PMID:3512", "title": "The effect of pH on incorporation of galactose by a normal human cell line and cell lines from patients with defective galactose metabolism.", "content": "Incorporation of radioactive galactose into TCA-insoluble material of galactosemic fibroblasts is more sensitive to low pH than is the incorporation by normal human fibroblasts. This study was undertaken to determine (1) whether there was any pH which could correct or counteract the galactosemic defect relative to galactose incorporation, and (2) whether the low pH effect was specific for galactose metabolism or whether general cellular metabolism in galactosemic cells was more sensitive to low pH than that in normal cells. The pH dependencies of incorporation of radioactive galactose and glucose into cellular macromolecules were investigated in galactosemic and normal cells. Normal cells have a biphasic curve with respect to galactose incorporation with peaks at pH 7.0 and 8.5. Galactosemic cells have only the high pH peak. The maximum incorporation by galactosemic cells was never more than about 30% that seen by normal cells under the conditions of these experiments. Thus manipulation of the pH alone cannot correct the galactosemic defect. The rate of incorporation of radioactive galactose was studied in normal, galactosemic and galactokinase deficient cells, at pH 7.2 and at pH 6.3. At pH 7.2, galactosemic cells incorporate galactose at a linear rate which is 30 to 40% that of normal cells while incorporation by kinase-deficient cells is between 5 and 10% of normal. At pH 6.3, the incorporation is also linear. However, galactosemic cells now exhibit the same rate as kinase-deficient cells in which the low level of incorporation is unaffected by pH. These results suggest that incorporation of galactose by galactosemic cells at low pH is not due to metabolic death of the cells, but may be due to the inhibition of some specific step or steps along a metabolic route of galactose metabolism other than the Leloir pathway.", "contents": "The effect of pH on incorporation of galactose by a normal human cell line and cell lines from patients with defective galactose metabolism. Incorporation of radioactive galactose into TCA-insoluble material of galactosemic fibroblasts is more sensitive to low pH than is the incorporation by normal human fibroblasts. This study was undertaken to determine (1) whether there was any pH which could correct or counteract the galactosemic defect relative to galactose incorporation, and (2) whether the low pH effect was specific for galactose metabolism or whether general cellular metabolism in galactosemic cells was more sensitive to low pH than that in normal cells. The pH dependencies of incorporation of radioactive galactose and glucose into cellular macromolecules were investigated in galactosemic and normal cells. Normal cells have a biphasic curve with respect to galactose incorporation with peaks at pH 7.0 and 8.5. Galactosemic cells have only the high pH peak. The maximum incorporation by galactosemic cells was never more than about 30% that seen by normal cells under the conditions of these experiments. Thus manipulation of the pH alone cannot correct the galactosemic defect. The rate of incorporation of radioactive galactose was studied in normal, galactosemic and galactokinase deficient cells, at pH 7.2 and at pH 6.3. At pH 7.2, galactosemic cells incorporate galactose at a linear rate which is 30 to 40% that of normal cells while incorporation by kinase-deficient cells is between 5 and 10% of normal. At pH 6.3, the incorporation is also linear. However, galactosemic cells now exhibit the same rate as kinase-deficient cells in which the low level of incorporation is unaffected by pH. These results suggest that incorporation of galactose by galactosemic cells at low pH is not due to metabolic death of the cells, but may be due to the inhibition of some specific step or steps along a metabolic route of galactose metabolism other than the Leloir pathway."}
{"id": "PMID:3514", "title": "Chromatography of hemoglobins on CM-cellulose with bis-tris and sodium chloride developers.", "content": "CM-Cellulose as an ion-exchange medium with Bis-tris as buffer and a gradient of sodium chloride provides a versatile system for the chromatography of hemoglobins. Changes in pH, Bis-tris concentration, and slope of the sodium chloride grandient provide means for markedly altering chromatographic behavior for special separations. Examples are given of the application of the method to normal samples and to those with hemoglobinopathies.", "contents": "Chromatography of hemoglobins on CM-cellulose with bis-tris and sodium chloride developers. CM-Cellulose as an ion-exchange medium with Bis-tris as buffer and a gradient of sodium chloride provides a versatile system for the chromatography of hemoglobins. Changes in pH, Bis-tris concentration, and slope of the sodium chloride grandient provide means for markedly altering chromatographic behavior for special separations. Examples are given of the application of the method to normal samples and to those with hemoglobinopathies."}
{"id": "PMID:3515", "title": "The determination of phanquone in biological material by gas-liquid chromatography.", "content": "A gas-liquid chromatographic method for the quantitative determination of phanquone is described, based on the formation of a dimethoxine prior to its extraction from biological material. The sensitivity of the procedure is about 15 ng/ml in biological fluid.", "contents": "The determination of phanquone in biological material by gas-liquid chromatography. A gas-liquid chromatographic method for the quantitative determination of phanquone is described, based on the formation of a dimethoxine prior to its extraction from biological material. The sensitivity of the procedure is about 15 ng/ml in biological fluid."}
{"id": "PMID:3516", "title": "Stability of fluorescent antibody conjugates stored under various conditions.", "content": "Two experiments were carried out to determine the stability of fluorescent antibody conjugates. In experiment 1, Francisella tularemia conjugates in the lyophilized state retained their original staining titer for 1,294 days when stored at 25, 4 to 5, and -20 C; at 37 C the conjugates were stable for at least 65 days. In the liquid state at pH 7.4 and 8.0 these conjugates were stable for 1,294 days at 4 to 5 and -20 C, whereas those stored at 25 C remained stable through days 473 and 160 of storage, respectively, after which the staining titer gradually dropped. In experiment 2 five previously lyophilized conjugates were rehydrated with three different diluents and stored at 4 to 5 C for up to 600 days at their working dilutions. All of these conjugates retained their original staining titer during the test period except an anti-human globulin conjugate rehydrated with phosphate-buffered saline. Recommendations are made for the long-term storage of fluorescent antibody conjugates.", "contents": "Stability of fluorescent antibody conjugates stored under various conditions. Two experiments were carried out to determine the stability of fluorescent antibody conjugates. In experiment 1, Francisella tularemia conjugates in the lyophilized state retained their original staining titer for 1,294 days when stored at 25, 4 to 5, and -20 C; at 37 C the conjugates were stable for at least 65 days. In the liquid state at pH 7.4 and 8.0 these conjugates were stable for 1,294 days at 4 to 5 and -20 C, whereas those stored at 25 C remained stable through days 473 and 160 of storage, respectively, after which the staining titer gradually dropped. In experiment 2 five previously lyophilized conjugates were rehydrated with three different diluents and stored at 4 to 5 C for up to 600 days at their working dilutions. All of these conjugates retained their original staining titer during the test period except an anti-human globulin conjugate rehydrated with phosphate-buffered saline. Recommendations are made for the long-term storage of fluorescent antibody conjugates."}
{"id": "PMID:3517", "title": "Inactivation of viruses in serum with binary ethyleneimine.", "content": "The inactivation os six strains from three different groups of viruses with 0.001 M binary ethyleneimine at 37 C proceeded at the same rate in either bovine serum or cell culture medium. The inactivant did not impair the growth-promoting capacity of bovine serum used in cell culture, nor did it affect the antibody activity of guinea pig hyperimmune serum.", "contents": "Inactivation of viruses in serum with binary ethyleneimine. The inactivation os six strains from three different groups of viruses with 0.001 M binary ethyleneimine at 37 C proceeded at the same rate in either bovine serum or cell culture medium. The inactivant did not impair the growth-promoting capacity of bovine serum used in cell culture, nor did it affect the antibody activity of guinea pig hyperimmune serum."}
{"id": "PMID:3518", "title": "Inorganic phosphate homeostasis. Renal adaptation to the dietary intake in intact and thyroparathyroidectomized rats.", "content": "The possibility of renal tubular adaptation to variations in dietary inorganic phosphate (Pi) was investigated in intact and thyroparathyroidectomized (TPTX) rats pair-fed diets containing low, normal, and high amounts of Pi for periods up to 10 days. Clearances were measured before and during active i.v. infusions with Pi in conscious animals. Thus tubular reabsorption of phosphate (TRPi) could be assessed over a wide range of plasma phosphate concentrations ([Pi]P1). It was found that the renal tubule could adapt its capacity to transport Pi according to the dietary Pi: TRPi was always higher, for a given [Pi]P1, in the animals fed low than in those fed higher Pi diets. This diet-induced modification also occurred in the absence of thyroparathyroid glands, in the presence of the same calcemia and urinary pH, and during marked extracellular volume expansion. A time-course study in rats TPTX both before and during the administration of the experimental diets showed that a difference in the tubular handling of Pi was detectable as early as 3 days after switching the animals from a normal to low- or high-Pi diets. These results indicate that factors other than parathyroid hormone are implicated in the tubular response to variations in the dietary intake of inorganic phosphate.", "contents": "Inorganic phosphate homeostasis. Renal adaptation to the dietary intake in intact and thyroparathyroidectomized rats. The possibility of renal tubular adaptation to variations in dietary inorganic phosphate (Pi) was investigated in intact and thyroparathyroidectomized (TPTX) rats pair-fed diets containing low, normal, and high amounts of Pi for periods up to 10 days. Clearances were measured before and during active i.v. infusions with Pi in conscious animals. Thus tubular reabsorption of phosphate (TRPi) could be assessed over a wide range of plasma phosphate concentrations ([Pi]P1). It was found that the renal tubule could adapt its capacity to transport Pi according to the dietary Pi: TRPi was always higher, for a given [Pi]P1, in the animals fed low than in those fed higher Pi diets. This diet-induced modification also occurred in the absence of thyroparathyroid glands, in the presence of the same calcemia and urinary pH, and during marked extracellular volume expansion. A time-course study in rats TPTX both before and during the administration of the experimental diets showed that a difference in the tubular handling of Pi was detectable as early as 3 days after switching the animals from a normal to low- or high-Pi diets. These results indicate that factors other than parathyroid hormone are implicated in the tubular response to variations in the dietary intake of inorganic phosphate."}
{"id": "PMID:3519", "title": "Effect of beta adrenergic blockade on renin response to renal nerve stimulation.", "content": "The ability of d,l-propranolol to block renin secretion in response to various extrarenal stimuli, such as hemorrhage and hypoglycemia, has been interpreted to indicate the presence of an intrarenal beta receptor regulating renin release. However, two problems complicate this interpretation: (a) the stimuli have effects outside the kidney, and (b) d,l-propranolol has a local anesthetic, as well as a beta adrenergic blocking, action. In the present study, the effects of a purely intrarenal stimulus, in the form of renal nerve stimulation (RNS), on renin secretion was examined. The effects of d,l-propranolol (anesthetic and beta-blocking activity), l-propranolol (beta-blocking activity only), and d-propranolol (local anesthetic activity only) on the renin response to RNS were examined. In a control group of animals, two sequential RNS increased mean renin secretion from 401 to 1,255 U/min (P less than 0.25) and from 220 to 2,179 U/min (P less than 0.01). In a second group the first RNS increased renin secretion from 201 to 1,181 U/min (P less than 0.01), but after d,l-propranolol was given RNS did not significantly alter renin secretion (33 to 55 U/min). In a third group the initial RNS increased renin secretion from 378 to 1,802 U/min (P less than 0.025), but after l-propranolol was given RNS had no significant effect on renin secretion (84 to 51 U/min). A fourth group of dogs showed a rise in renin secretion from 205 to 880 U/min (P less than 0.001) in response to the first RNS, while the second RNS, given after an infusion of d-propranolol, caused a rise in renin secretion from 80 to 482 (P less than 0.005). The nature of the electrical stimulus was consistent in all groups and caused no detectable changes in renal or systemic hemodynamics or in urinary electrolyte excretion. The results, therefore, indicate that renin secretion can be stimulated through intrarenal beta receptors independent of changes in systemic or renal hemodynamics or in tubular sodium reabsorption. Hence the effect of beta stimulation on renin secretion would appear to result from a direct action on the renin-secreting cells of the juxtaglomerular apparatus.", "contents": "Effect of beta adrenergic blockade on renin response to renal nerve stimulation. The ability of d,l-propranolol to block renin secretion in response to various extrarenal stimuli, such as hemorrhage and hypoglycemia, has been interpreted to indicate the presence of an intrarenal beta receptor regulating renin release. However, two problems complicate this interpretation: (a) the stimuli have effects outside the kidney, and (b) d,l-propranolol has a local anesthetic, as well as a beta adrenergic blocking, action. In the present study, the effects of a purely intrarenal stimulus, in the form of renal nerve stimulation (RNS), on renin secretion was examined. The effects of d,l-propranolol (anesthetic and beta-blocking activity), l-propranolol (beta-blocking activity only), and d-propranolol (local anesthetic activity only) on the renin response to RNS were examined. In a control group of animals, two sequential RNS increased mean renin secretion from 401 to 1,255 U/min (P less than 0.25) and from 220 to 2,179 U/min (P less than 0.01). In a second group the first RNS increased renin secretion from 201 to 1,181 U/min (P less than 0.01), but after d,l-propranolol was given RNS did not significantly alter renin secretion (33 to 55 U/min). In a third group the initial RNS increased renin secretion from 378 to 1,802 U/min (P less than 0.025), but after l-propranolol was given RNS had no significant effect on renin secretion (84 to 51 U/min). A fourth group of dogs showed a rise in renin secretion from 205 to 880 U/min (P less than 0.001) in response to the first RNS, while the second RNS, given after an infusion of d-propranolol, caused a rise in renin secretion from 80 to 482 (P less than 0.005). The nature of the electrical stimulus was consistent in all groups and caused no detectable changes in renal or systemic hemodynamics or in urinary electrolyte excretion. The results, therefore, indicate that renin secretion can be stimulated through intrarenal beta receptors independent of changes in systemic or renal hemodynamics or in tubular sodium reabsorption. Hence the effect of beta stimulation on renin secretion would appear to result from a direct action on the renin-secreting cells of the juxtaglomerular apparatus."}
{"id": "PMID:3520", "title": "Identification and characterization of a bile acid receptor in isolated liver surface membranes.", "content": "It is generally assumed that hepatic transport of bile acids is a carrier-mediated process. However, the basic mechanisms by which these organic anions are translocated across the liver cell surface membrane are not well understood. Since carrier-mediated transport involved binding of the transported molecule to specific receptor sites, we have investigated the possibility that bile acid receptors are present in liver surface membranes. Isolated liver surface membranes were incubated at 4 degrees C with [14C]cholic acid and [14C]taurocholic acid, and membrane-boudn bile acid was separated from free by a rapid ultrafiltration technique through glass-fiber filters. Specific bile acid binding is rapid and reversible and represents approximately 80% of the total bile acid bound to liver surface membranes. Taurocholic acid binding is independent of the medium pH, while cholic acid binding demonstrates an optimum at pH 6.0. Analysis of equilibrium data for both cholic and taurocholic acid binding indicates that specific binding is saturable and consistent with Michaelis-Menten kinetics, while nonspecific binding is nonsaturable. Apparent maximal binding capacity and dissociation constant values indicate a large capacity system of receptors that have an affinity for bile acids comparable to that of the hepatic transport mechanism. Scatchard analysis of the saturation kinetics as well as inhibition studies suggest that bile acids bind to a single and noninteracting class of anion that competes with bile acids for hepatic uptake, also inhibits cholic acid binding. In contrast, no inhibition was demonstrated with indocyanine green and probenecid. Specific bile acid binding is enriched and primarily located in liver surface membranes and found only in tissues involved in bile acid transport. Specific bile acid binding is independnet of Na+, Ca2+, and Mg2+ and does not require metabolic energy. In addition, thiol groups and disulfide are not required for activity at the binding site. However, specific bile acid binding is markedly decreased by low concentrations of proteolytic enzymes and is also decreased by the action of neuraminidase and phospholipases A and C. These results are consistent with the existence of a homogeneous bile acid receptor protein in liver surface membranes. The primary surface membrane location of this receptor, its binding properties, and its ligand specificity suggest that bile acid binding to this receptor may represent the initial interaction in bile acid transport across liver surface membranes.", "contents": "Identification and characterization of a bile acid receptor in isolated liver surface membranes. It is generally assumed that hepatic transport of bile acids is a carrier-mediated process. However, the basic mechanisms by which these organic anions are translocated across the liver cell surface membrane are not well understood. Since carrier-mediated transport involved binding of the transported molecule to specific receptor sites, we have investigated the possibility that bile acid receptors are present in liver surface membranes. Isolated liver surface membranes were incubated at 4 degrees C with [14C]cholic acid and [14C]taurocholic acid, and membrane-boudn bile acid was separated from free by a rapid ultrafiltration technique through glass-fiber filters. Specific bile acid binding is rapid and reversible and represents approximately 80% of the total bile acid bound to liver surface membranes. Taurocholic acid binding is independent of the medium pH, while cholic acid binding demonstrates an optimum at pH 6.0. Analysis of equilibrium data for both cholic and taurocholic acid binding indicates that specific binding is saturable and consistent with Michaelis-Menten kinetics, while nonspecific binding is nonsaturable. Apparent maximal binding capacity and dissociation constant values indicate a large capacity system of receptors that have an affinity for bile acids comparable to that of the hepatic transport mechanism. Scatchard analysis of the saturation kinetics as well as inhibition studies suggest that bile acids bind to a single and noninteracting class of anion that competes with bile acids for hepatic uptake, also inhibits cholic acid binding. In contrast, no inhibition was demonstrated with indocyanine green and probenecid. Specific bile acid binding is enriched and primarily located in liver surface membranes and found only in tissues involved in bile acid transport. Specific bile acid binding is independnet of Na+, Ca2+, and Mg2+ and does not require metabolic energy. In addition, thiol groups and disulfide are not required for activity at the binding site. However, specific bile acid binding is markedly decreased by low concentrations of proteolytic enzymes and is also decreased by the action of neuraminidase and phospholipases A and C. These results are consistent with the existence of a homogeneous bile acid receptor protein in liver surface membranes. The primary surface membrane location of this receptor, its binding properties, and its ligand specificity suggest that bile acid binding to this receptor may represent the initial interaction in bile acid transport across liver surface membranes."}
{"id": "PMID:3521", "title": "A brief anxiety rating scale in evaluating anxiolytics.", "content": "The Wang Anxiety Rating Scale (WARS) was designed to evaluate degrees of anxiety in patients receiving anxiolytic medication. WARS contains 12 pertinent symptoms of anxiety: nervousness, restlessness, excitability, irritability, worrying, disturbed concentration, palpitation, insomnia, hostility, tremors, smoking, and excessive perspiration. Frequently encountered side effects of anxiolytic medications are excluded. The validity of the WARS was determined by correlation with the Hamilton Anxiety Rating Scale (HARS) in a single-blind study in which 20 chronically anxious patients consecutively received placebo (three days), 15 mg clorazepate dipotassium (two weeks), and 22.5 mg clorazepate dipotassium (two weeks). Both anxiety scales, a side effect scale, and a global assessment were completed at regular intervals (periods 0-6). Results show (1) highly significant correlation (P less than 0.001) between WARS and HARS for periods 1-6; (2) greater correlation between HARS and side effect scale than between WARS and side effect scale; (3) greater correlation between WARS and global assessment than between HARS and global assessment; correlated changes in scores for WARS, HARS, and global assessment demonstrate efficacy of active medication.", "contents": "A brief anxiety rating scale in evaluating anxiolytics. The Wang Anxiety Rating Scale (WARS) was designed to evaluate degrees of anxiety in patients receiving anxiolytic medication. WARS contains 12 pertinent symptoms of anxiety: nervousness, restlessness, excitability, irritability, worrying, disturbed concentration, palpitation, insomnia, hostility, tremors, smoking, and excessive perspiration. Frequently encountered side effects of anxiolytic medications are excluded. The validity of the WARS was determined by correlation with the Hamilton Anxiety Rating Scale (HARS) in a single-blind study in which 20 chronically anxious patients consecutively received placebo (three days), 15 mg clorazepate dipotassium (two weeks), and 22.5 mg clorazepate dipotassium (two weeks). Both anxiety scales, a side effect scale, and a global assessment were completed at regular intervals (periods 0-6). Results show (1) highly significant correlation (P less than 0.001) between WARS and HARS for periods 1-6; (2) greater correlation between HARS and side effect scale than between WARS and side effect scale; (3) greater correlation between WARS and global assessment than between HARS and global assessment; correlated changes in scores for WARS, HARS, and global assessment demonstrate efficacy of active medication."}
{"id": "PMID:3545", "title": "The changing pattern of bacterial sepsis since the introduction of antibiotic therapy.", "content": "During the six-year period, 1968-1973, sepsis developed in 1 of every 80 patients admitted to the Presbyterian Hospital, New York. In 1 of 133 patients the sepsis was due to Gram-positive organisms, and in 1 of 188 patients to Gram-negative organisms. The mortality rate for Gram-positive cases was 4.4 percent, for Gram-negative cases 19.1 percent, and for urologic cases 15.3 percent (versus 56.25 percent in 1959-1964). Data are presented on the relative incidences of involved pathogens in 1740 cases of Gram-positive sepsis /78 deaths), and in 1236 cases of Gram-negative sepsis (205 deaths). The lowering of the sepsis mortality rate has been the result of preventative measures, early diagnosis, and vigorous treatment. Treatment includes the correction of acidosis and anoxia, early administration of bactericidal antibiotics, and restoration of the microcirculation by administration of corticosteroids, beta-adrenergic drugs, and appropriate diuretics.", "contents": "The changing pattern of bacterial sepsis since the introduction of antibiotic therapy. During the six-year period, 1968-1973, sepsis developed in 1 of every 80 patients admitted to the Presbyterian Hospital, New York. In 1 of 133 patients the sepsis was due to Gram-positive organisms, and in 1 of 188 patients to Gram-negative organisms. The mortality rate for Gram-positive cases was 4.4 percent, for Gram-negative cases 19.1 percent, and for urologic cases 15.3 percent (versus 56.25 percent in 1959-1964). Data are presented on the relative incidences of involved pathogens in 1740 cases of Gram-positive sepsis /78 deaths), and in 1236 cases of Gram-negative sepsis (205 deaths). The lowering of the sepsis mortality rate has been the result of preventative measures, early diagnosis, and vigorous treatment. Treatment includes the correction of acidosis and anoxia, early administration of bactericidal antibiotics, and restoration of the microcirculation by administration of corticosteroids, beta-adrenergic drugs, and appropriate diuretics."}
{"id": "PMID:3546", "title": "[Has the pH meter replaced the Apgar score?].", "content": "The introduction of measuring the pH appears to place it in competition with Apgar scoring because of its precision. A study of this which has been carried out has illustrated that there are two different criteria for assessing the state of the infant at birth. The usual agreement between pH values and Apgar scoring can be broken when clinical fetal distress has become established before metabolic equilibrium of the infant has become modified. In these circumstances the Apgar score will be bad while the pH will be good.", "contents": "[Has the pH meter replaced the Apgar score?]. The introduction of measuring the pH appears to place it in competition with Apgar scoring because of its precision. A study of this which has been carried out has illustrated that there are two different criteria for assessing the state of the infant at birth. The usual agreement between pH values and Apgar scoring can be broken when clinical fetal distress has become established before metabolic equilibrium of the infant has become modified. In these circumstances the Apgar score will be bad while the pH will be good."}
{"id": "PMID:3604", "title": "Kinetics of the antibody response to type III pneumococcal polysaccharide. I. Evidence that suppressor cells function by inhibiting the recruitment and proliferation of antibody-producing cells.", "content": "For the first 126 hr after immunization of mice with an optimally immunogenic dose (0.5 mug) of Type III pneumococcal polysaccharide (SSS-III), splenic antibody-forming PFC and serum antibody levels were measured at 2- and 8-hr intervals, respectively. PFC were detected at 28 hr after immunization and then increased through 86 hr after immunization; thereafter, the number of PFC remained nearly constant for the next 20 to 24 hr, and then began to decline. In contrast, serum antibody was first detected 60 hr after immunization. The accumulation of serum antibody continued to lag behind the increase in numbers of PFC by 16 to 20 hr until maximal serum antibody levels were attained; curves fitted to the values obtained for each parameter were nearly parallel.", "contents": "Kinetics of the antibody response to type III pneumococcal polysaccharide. I. Evidence that suppressor cells function by inhibiting the recruitment and proliferation of antibody-producing cells. For the first 126 hr after immunization of mice with an optimally immunogenic dose (0.5 mug) of Type III pneumococcal polysaccharide (SSS-III), splenic antibody-forming PFC and serum antibody levels were measured at 2- and 8-hr intervals, respectively. PFC were detected at 28 hr after immunization and then increased through 86 hr after immunization; thereafter, the number of PFC remained nearly constant for the next 20 to 24 hr, and then began to decline. In contrast, serum antibody was first detected 60 hr after immunization. The accumulation of serum antibody continued to lag behind the increase in numbers of PFC by 16 to 20 hr until maximal serum antibody levels were attained; curves fitted to the values obtained for each parameter were nearly parallel."}
{"id": "PMID:3605", "title": "Influence of protein restriction on immune functions in NZB mice.", "content": "The influence of a low protein (6%) diet on the immunologic function of NZB mice was investigated. The low protein intake was associated with decreased weight gain in both male and female NZB mice. The mice fed the low protein diet did not develop splenomegaly, which generally occurs by 7 to 10 months of age in NZB mice fed a normal amount of protein. Further, 7- to 10-month-old NZB mice fed the low protein(6%) diet, maintained: 1) more vigorous antibody production to sheep red blood cells; 2) greater capacity to produce graft-vs-host reactions, and 3) more vigorous cell-mediated \"killer\" cell immunity after immunization against DBA/2 mastocytoma cells than did NZB mice on a normal (22%) protein diet. The decrease of PHA and Con A response which normally occurs with aging in NZB mice was abrogated to some degree by protein restriction. However, response to LPS, which also declines with age in NZB mice, did not appear to be influenced by diet.", "contents": "Influence of protein restriction on immune functions in NZB mice. The influence of a low protein (6%) diet on the immunologic function of NZB mice was investigated. The low protein intake was associated with decreased weight gain in both male and female NZB mice. The mice fed the low protein diet did not develop splenomegaly, which generally occurs by 7 to 10 months of age in NZB mice fed a normal amount of protein. Further, 7- to 10-month-old NZB mice fed the low protein(6%) diet, maintained: 1) more vigorous antibody production to sheep red blood cells; 2) greater capacity to produce graft-vs-host reactions, and 3) more vigorous cell-mediated \"killer\" cell immunity after immunization against DBA/2 mastocytoma cells than did NZB mice on a normal (22%) protein diet. The decrease of PHA and Con A response which normally occurs with aging in NZB mice was abrogated to some degree by protein restriction. However, response to LPS, which also declines with age in NZB mice, did not appear to be influenced by diet."}
{"id": "PMID:3606", "title": "Characterization of cells that suppress the cytotoxic activity of T lymphocytes. I. Quantitative measurement of inhibitor cells.", "content": "Target cell lysis by sensitized cytolytic T lymphocytes (CTL) may be conveniently quantitated by 51Cr release. By fitting to the formula, P (% specfic release) = 100 (1-e-Nat) one obtains alpha, the relative frequency of CTL in N lymphoid cells. Using a microassay and murine sarcoma target cells, we observed an unexpected decrease in lysis whenever effectors obtained from a graft-vs-host reaction were tested at high concentrations. This inhibition was not observed with CTL generated by an MLC reaction. Inhibition could not be explained by nonspecific mechanical 'crowding', reutilization of released isotope, suppression of release from dead target cells, or the particular strain combination and target used. By modifying the formula to allow suppression of CTL by a stochastic cell-cell interaction with suppessor cell, we found that P = 100 (1-e-Nate-Ngamma) adequately fitted the data, where Ngamma is proportional to inhibitor content. An 18- to 24-hr incubation at 37 degrees C but not 4 degrees C allowed selective depletion or enrichment of inhibitors; in mixing experiments, both parameters Nalpha t and Ngamma behaved stoichiometrically as independent cellular properties. The inhibitor was resistant to concentrations of anti-T cell (RAMG) serum + complement which killed -TL. A similar inhibitor arose in vivo during an anti-tumour allograft response. The ability to quantitate CTL and inhibitor activities from titration curves provides a technique for studying the identity and mechanism of suppressor cells acting at the effector stage of cell-mediated immunity.", "contents": "Characterization of cells that suppress the cytotoxic activity of T lymphocytes. I. Quantitative measurement of inhibitor cells. Target cell lysis by sensitized cytolytic T lymphocytes (CTL) may be conveniently quantitated by 51Cr release. By fitting to the formula, P (% specfic release) = 100 (1-e-Nat) one obtains alpha, the relative frequency of CTL in N lymphoid cells. Using a microassay and murine sarcoma target cells, we observed an unexpected decrease in lysis whenever effectors obtained from a graft-vs-host reaction were tested at high concentrations. This inhibition was not observed with CTL generated by an MLC reaction. Inhibition could not be explained by nonspecific mechanical 'crowding', reutilization of released isotope, suppression of release from dead target cells, or the particular strain combination and target used. By modifying the formula to allow suppression of CTL by a stochastic cell-cell interaction with suppessor cell, we found that P = 100 (1-e-Nate-Ngamma) adequately fitted the data, where Ngamma is proportional to inhibitor content. An 18- to 24-hr incubation at 37 degrees C but not 4 degrees C allowed selective depletion or enrichment of inhibitors; in mixing experiments, both parameters Nalpha t and Ngamma behaved stoichiometrically as independent cellular properties. The inhibitor was resistant to concentrations of anti-T cell (RAMG) serum + complement which killed -TL. A similar inhibitor arose in vivo during an anti-tumour allograft response. The ability to quantitate CTL and inhibitor activities from titration curves provides a technique for studying the identity and mechanism of suppressor cells acting at the effector stage of cell-mediated immunity."}
{"id": "PMID:3607", "title": "IgM-mediated, T cell-independent suppression of humoral immunity.", "content": "The immunological unreactive state occurring in (T,G)-A-L nonresponder mice after secondary antigen challenge was investigated. Syngeneic IgM anti-(T,G)-A-L antibody-containing plasma, transferred at the time of the time of primary challenge, induced persistent suppression of autologous specific antibody production. Removal of plasma IgM with goat anti-mu antisera removed the ability of the plasma to supress. The induction and maintenance of the suppressed state were not different in thymectomized or sham-thymectomized animals. Primed animals subjected to graft-vs-host reaction (GVHR) at the time of secondary challenge switched over to IgG production. Animals suppressed by passive antibody transfer reacted to GVHR, at the time of secondary challenge, with specific IgM but not IgG antibody production. Transfused normal spleen cells partially abrogated suppression only when (suppressed) hosts had been lethally irradiated. Spleen cells from antigen-plus-antibody suppressed donors, upon transfer to previously normal, syngeneic hosts, were less immunocompetent than spleen cells from untreated donors. These data are consistent with a model of IgM mediated, T cell-independent persistent suppression of humoral immunity.", "contents": "IgM-mediated, T cell-independent suppression of humoral immunity. The immunological unreactive state occurring in (T,G)-A-L nonresponder mice after secondary antigen challenge was investigated. Syngeneic IgM anti-(T,G)-A-L antibody-containing plasma, transferred at the time of the time of primary challenge, induced persistent suppression of autologous specific antibody production. Removal of plasma IgM with goat anti-mu antisera removed the ability of the plasma to supress. The induction and maintenance of the suppressed state were not different in thymectomized or sham-thymectomized animals. Primed animals subjected to graft-vs-host reaction (GVHR) at the time of secondary challenge switched over to IgG production. Animals suppressed by passive antibody transfer reacted to GVHR, at the time of secondary challenge, with specific IgM but not IgG antibody production. Transfused normal spleen cells partially abrogated suppression only when (suppressed) hosts had been lethally irradiated. Spleen cells from antigen-plus-antibody suppressed donors, upon transfer to previously normal, syngeneic hosts, were less immunocompetent than spleen cells from untreated donors. These data are consistent with a model of IgM mediated, T cell-independent persistent suppression of humoral immunity."}
{"id": "PMID:3609", "title": "Secondary IgG responses to type III pneumococcal polysaccharide. II. Different cellular requirements for induction and elicitation.", "content": "Mice primed with a thymus- (T) dependent form of Type III pneumococcal polysaccharide (S3), i.e., S3 coupled to erythrocytes (S3-RBC) produce S3-specific IgG antibody after secondary challenge with either S3 or S3-RBC. The production of IgG antibody by mice challenged with S3 was shown to be T independent since secondary responses were enhanced when mice were treated with anti-lymphocyte serum (ALS) at the time of secondary challenge with S3 and T-depleted spleen cells responded as well as unfractionated spleen cells to S3 in an adoptive transfer system. Secondary S3-specific IgG responses in mice challenged with S3-RBC were shown to be T dependent by the same criteria. The results obtained by using S3 as the antigen indicate that IgG-producing B cells (B lambda cells) can recognize and respond to antigen in the absence of helper T cells. On the other hand, T cells were required for the induction of S3-specific memory B lambda cells since mice depleted of T cells by treatment with ALS at the time of priming with S3-RBC failed to produce S3-specific IgG antibody after secondary challenge with either S3-specific IgG antibody after secondary chall-nge with either S3 or S3rbc. Since RBC-specific memory cells were induced in T-deprived mice the results suggest that T cell regulation of IgG antibody production may vary for different antigens.", "contents": "Secondary IgG responses to type III pneumococcal polysaccharide. II. Different cellular requirements for induction and elicitation. Mice primed with a thymus- (T) dependent form of Type III pneumococcal polysaccharide (S3), i.e., S3 coupled to erythrocytes (S3-RBC) produce S3-specific IgG antibody after secondary challenge with either S3 or S3-RBC. The production of IgG antibody by mice challenged with S3 was shown to be T independent since secondary responses were enhanced when mice were treated with anti-lymphocyte serum (ALS) at the time of secondary challenge with S3 and T-depleted spleen cells responded as well as unfractionated spleen cells to S3 in an adoptive transfer system. Secondary S3-specific IgG responses in mice challenged with S3-RBC were shown to be T dependent by the same criteria. The results obtained by using S3 as the antigen indicate that IgG-producing B cells (B lambda cells) can recognize and respond to antigen in the absence of helper T cells. On the other hand, T cells were required for the induction of S3-specific memory B lambda cells since mice depleted of T cells by treatment with ALS at the time of priming with S3-RBC failed to produce S3-specific IgG antibody after secondary challenge with either S3-specific IgG antibody after secondary chall-nge with either S3 or S3rbc. Since RBC-specific memory cells were induced in T-deprived mice the results suggest that T cell regulation of IgG antibody production may vary for different antigens."}
{"id": "PMID:3610", "title": "The effect of Bordetella pertussis on the antibody response in mice to type III pneumococcal polysaccharide.", "content": "The effect of an i.p. injection of Bordetella pertussis on the primary humoral immune response in mice to the thymus-independent antigen SIII has been studied. Suppression of the antibody response occurred when pertussis cells were injected at the same time as an optimal immunizing dose of SIII. In contrast, the antibody response to high doses of SIII was enhanced by B. pertussis. When SIII alone was injected, only 19S antibody was detected. However, when B. pertussis was administered with either optimal or high doses of SIII, 7S as well as 19S antibody against SIII was produced.", "contents": "The effect of Bordetella pertussis on the antibody response in mice to type III pneumococcal polysaccharide. The effect of an i.p. injection of Bordetella pertussis on the primary humoral immune response in mice to the thymus-independent antigen SIII has been studied. Suppression of the antibody response occurred when pertussis cells were injected at the same time as an optimal immunizing dose of SIII. In contrast, the antibody response to high doses of SIII was enhanced by B. pertussis. When SIII alone was injected, only 19S antibody was detected. However, when B. pertussis was administered with either optimal or high doses of SIII, 7S as well as 19S antibody against SIII was produced."}
{"id": "PMID:3611", "title": "Immunology of DNA. I. The influence of reaction conditions on the Farr assay as used for the detection of anti-ds DNA.", "content": "The sensitivity and the specificity of the Farr assay for the detection of antibodies to double stranded (ds) DNA depends very much on the reaction conditions. The interaction between ds DNA and anti-ds DNA is inhibited when ionic strength and pH are increased. ds DNA is bound by normal sera at ionic strength lower than 0.11 M NaCl and at physiological ionic strength when the pH is lower than 7.2. Substantial binding of DNA by normal serum takes place in barbitone, borate or Tris-HCl buffers at concentrations of 30 mM or higher, even at a pH higher than 7.2. Such binding is due to Clq and is only partially prevented by heating the serum for 30 min at 56 degrees C, but 10 mM phosphate in the incubation mixture completely prevents it. Standardization of ionic strength, pH, phosphate concentration, incubation volume and DNA-serum ratio enhances the diagnostic usefulness of the Farr assay.", "contents": "Immunology of DNA. I. The influence of reaction conditions on the Farr assay as used for the detection of anti-ds DNA. The sensitivity and the specificity of the Farr assay for the detection of antibodies to double stranded (ds) DNA depends very much on the reaction conditions. The interaction between ds DNA and anti-ds DNA is inhibited when ionic strength and pH are increased. ds DNA is bound by normal sera at ionic strength lower than 0.11 M NaCl and at physiological ionic strength when the pH is lower than 7.2. Substantial binding of DNA by normal serum takes place in barbitone, borate or Tris-HCl buffers at concentrations of 30 mM or higher, even at a pH higher than 7.2. Such binding is due to Clq and is only partially prevented by heating the serum for 30 min at 56 degrees C, but 10 mM phosphate in the incubation mixture completely prevents it. Standardization of ionic strength, pH, phosphate concentration, incubation volume and DNA-serum ratio enhances the diagnostic usefulness of the Farr assay."}
{"id": "PMID:3612", "title": "A Doppler assay for the antigen--antibody reaction.", "content": "The specific combination of antigen with antibody was detected rapidly and with high sensitivity by an assay based on particle electrophoresis and laser light scattering. Antibody attachment to dilute suspensions of submicroscopic polystyrene spheres coated with antigen was detected as changes in the Doppler shift of scattered laser light when the suspended particles were subjected to an electric field. Antibody or antigen concentrations in the range of 5--10 nanograms per ml can be detected in 30 min. The principal experimental features of the technique are described and include: a) choice of particles; b) coating procedures; c) treatment for non-specificity; d) choice of measurement medium.", "contents": "A Doppler assay for the antigen--antibody reaction. The specific combination of antigen with antibody was detected rapidly and with high sensitivity by an assay based on particle electrophoresis and laser light scattering. Antibody attachment to dilute suspensions of submicroscopic polystyrene spheres coated with antigen was detected as changes in the Doppler shift of scattered laser light when the suspended particles were subjected to an electric field. Antibody or antigen concentrations in the range of 5--10 nanograms per ml can be detected in 30 min. The principal experimental features of the technique are described and include: a) choice of particles; b) coating procedures; c) treatment for non-specificity; d) choice of measurement medium."}
{"id": "PMID:3613", "title": "California arbovirus (La Crosse) infections. III. Epidemiology of California encephalitis in Minnesota.", "content": "Mosquitoes (eggs, larvae, and adults), small woodland animals, and residents of an area where California encephalitis is endemic were studied to elucidate the host-vector cycle of La Crosse virus. Elementary schoolchildren from surrounding communities and gray squirrels from another area were tested to compare the prevelence of serum antibodies to La Crosse virus in areas where the disease is endemic with the prevalence of these antibodies in areas where the disease is not endemic. From 1971 to 1974, eight isolations of La Crosse virus were made. Three of the isolates were from adult mosquitoes, one from Aedes triseriatus eggs, and four from A. triseriatus larvae. The isolation of virus from field-collected eggs and larvae confirms previous studies from Wisconsin that suggest that La Crosse virus overwinters in eggs of the mosquite A. triseriatus. In an area where California encephalitis is endemic, 10 of 19 small woodland animals (53%), which are the natural hosts of A. triseriatus, had hemagglutination-inhibiting and neutralizing antibodies to La Crosse virus. In contrast, none of 10 squirrels from an area where the disease is not endemic had such antibodies. Fourteen of 79 residents of this area (17.7%) had both types of antibody. Eleven of the 14 seropositive residents lived in one small sector of the community studied, an indication that foci of La Crosse virus activity may be very localized. Elementary schoolchildren from surrounding communitites had a significantly lower prevalence of hemagglutination-inhibiting antibody to La Crosse virus than did the residents of the area where California encephalitis was endemic.", "contents": "California arbovirus (La Crosse) infections. III. Epidemiology of California encephalitis in Minnesota. Mosquitoes (eggs, larvae, and adults), small woodland animals, and residents of an area where California encephalitis is endemic were studied to elucidate the host-vector cycle of La Crosse virus. Elementary schoolchildren from surrounding communities and gray squirrels from another area were tested to compare the prevelence of serum antibodies to La Crosse virus in areas where the disease is endemic with the prevalence of these antibodies in areas where the disease is not endemic. From 1971 to 1974, eight isolations of La Crosse virus were made. Three of the isolates were from adult mosquitoes, one from Aedes triseriatus eggs, and four from A. triseriatus larvae. The isolation of virus from field-collected eggs and larvae confirms previous studies from Wisconsin that suggest that La Crosse virus overwinters in eggs of the mosquite A. triseriatus. In an area where California encephalitis is endemic, 10 of 19 small woodland animals (53%), which are the natural hosts of A. triseriatus, had hemagglutination-inhibiting and neutralizing antibodies to La Crosse virus. In contrast, none of 10 squirrels from an area where the disease is not endemic had such antibodies. Fourteen of 79 residents of this area (17.7%) had both types of antibody. Eleven of the 14 seropositive residents lived in one small sector of the community studied, an indication that foci of La Crosse virus activity may be very localized. Elementary schoolchildren from surrounding communitites had a significantly lower prevalence of hemagglutination-inhibiting antibody to La Crosse virus than did the residents of the area where California encephalitis was endemic."}
{"id": "PMID:3614", "title": "Characterization of fatty acid desaturase activity in rat lung microsomes.", "content": "Preparations of rat lung microsomes containing 0.030-0.050 nmole of cytochromes P-450 and b5 per mg microsomal protein have been observed to contain significant levels of fatty acid desaturase activity. Both stearoyl CoA and palmitoyl CoA are desaturated to their monounsaturated analogues, oleic acid and palmitoleic acid, respectively. Activity (per mg microsomal protein) of the lung preparations varied according to the diet of the animals prior to killing in the order: fat free diet greater than normal rat chow greater than starvation. All preparations exhibited approximately 50% inhibition when incubated in the presence of 0.10 mM CN-. Maximal activity was obtained with the 0.50 mM NADH less activity with equal amounts of NADPH, and there was no synergistic interaction of NADH and NADPH together. The rate of desaturation was linear with protein concentrations between 0.15-1.5 mg microsomal protein/incubation at incubation times up to 8 min. A pH optimum range of 7.0-7.4 was observed. For all variables of fatty acid desaturase activity which were examined, the rate of desaturation of stearoyl CoA was approximately twice that for palmitoyl CoA. These results indicate that the same fatty acid desaturation system which is functional in the liver is also present in significant amounts in mammalian lungs.", "contents": "Characterization of fatty acid desaturase activity in rat lung microsomes. Preparations of rat lung microsomes containing 0.030-0.050 nmole of cytochromes P-450 and b5 per mg microsomal protein have been observed to contain significant levels of fatty acid desaturase activity. Both stearoyl CoA and palmitoyl CoA are desaturated to their monounsaturated analogues, oleic acid and palmitoleic acid, respectively. Activity (per mg microsomal protein) of the lung preparations varied according to the diet of the animals prior to killing in the order: fat free diet greater than normal rat chow greater than starvation. All preparations exhibited approximately 50% inhibition when incubated in the presence of 0.10 mM CN-. Maximal activity was obtained with the 0.50 mM NADH less activity with equal amounts of NADPH, and there was no synergistic interaction of NADH and NADPH together. The rate of desaturation was linear with protein concentrations between 0.15-1.5 mg microsomal protein/incubation at incubation times up to 8 min. A pH optimum range of 7.0-7.4 was observed. For all variables of fatty acid desaturase activity which were examined, the rate of desaturation of stearoyl CoA was approximately twice that for palmitoyl CoA. These results indicate that the same fatty acid desaturation system which is functional in the liver is also present in significant amounts in mammalian lungs."}
{"id": "PMID:3615", "title": "Effect of unilateral and bilateral castration and cryptorchidism on serum gonadotrophins in the rat.", "content": "The effects of unilateral and bilateral cryptorchidism and castration on serum concentrations of testosterone, FSH and LH in adult male rats were examined. The results provide no evidence for compensatory growth or development of the remaining scrotal testes up to 32 days after unilateral castration, although the scrotal testis of unilaterally cryptorchid rats showed enlargement when compared with those of control rats (P less than 0 - 05) at 32 days. Unilateral treatments had few significant effects on serum hormones, but testosterone was increased on day 4 (P less than 0 - 05) in unilaterally cryptorchid rats and on day 32 (P less than 0 - 05) in unilaterally castrated rats, compared with controls, and FSH levels were higher in unilaterally castrated rats on day 16 (P less than 0 - 05). Bilateral cryptorchidism caused an increase in serum FSH within 4 days (P less than 0 - 05) and in serum LH by 8 days (P less than 0-05) after surgery, with both hormones reaching levels double those found in control rats (P less than 0 - 01) by day 16, while testosterone levels were maintained at or above control values. Bilateral castration resulted in a marked decrease in testosterone levels (P less than 0 - 01) and a sharp increase in serum gonadotrophins. FSH had nearly doubled (P less than 0 - 01) and LH had increased fourfold (P less than 0 - 01) 4 days after castration, their levels reaching 773% (LH) and 287% (FSH) of control values by 32 days (P less than 0 - 01). The observations support the hypothesis of a separate, testosterone-independent feedback system of the testis on the hypophysis.", "contents": "Effect of unilateral and bilateral castration and cryptorchidism on serum gonadotrophins in the rat. The effects of unilateral and bilateral cryptorchidism and castration on serum concentrations of testosterone, FSH and LH in adult male rats were examined. The results provide no evidence for compensatory growth or development of the remaining scrotal testes up to 32 days after unilateral castration, although the scrotal testis of unilaterally cryptorchid rats showed enlargement when compared with those of control rats (P less than 0 - 05) at 32 days. Unilateral treatments had few significant effects on serum hormones, but testosterone was increased on day 4 (P less than 0 - 05) in unilaterally cryptorchid rats and on day 32 (P less than 0 - 05) in unilaterally castrated rats, compared with controls, and FSH levels were higher in unilaterally castrated rats on day 16 (P less than 0 - 05). Bilateral cryptorchidism caused an increase in serum FSH within 4 days (P less than 0 - 05) and in serum LH by 8 days (P less than 0-05) after surgery, with both hormones reaching levels double those found in control rats (P less than 0 - 01) by day 16, while testosterone levels were maintained at or above control values. Bilateral castration resulted in a marked decrease in testosterone levels (P less than 0 - 01) and a sharp increase in serum gonadotrophins. FSH had nearly doubled (P less than 0 - 01) and LH had increased fourfold (P less than 0 - 01) 4 days after castration, their levels reaching 773% (LH) and 287% (FSH) of control values by 32 days (P less than 0 - 01). The observations support the hypothesis of a separate, testosterone-independent feedback system of the testis on the hypophysis."}
{"id": "PMID:3616", "title": "Further evidence for histamine facilitating oestrogen action in the uterus.", "content": "The effect of doses of estradiol ranging from 0-0125 to 1-6 mug on the uterine weight of the spayed rat was studied 24 h after a single s.c. injection of the hormone. The lowest dose inducing a significant increase in uterine weight was 0-32 mug. When histamine dihydrochloride (50 mg) was simultaneously injected with the hormone, the effect of small doses of oestradiol (0-0125--0-2 mug) was significantly increased. When oestradiol and histamine were administered for 3 successive days, the uterine weight of animals receiving 0-0125 mug oestradiol, if compared with untreated controls, was increased only in the histamine-treated group. When 0-05 mug oestradiol was administered histamine did not modify the increase already produced by the hormone. Spermidine and burimamide, two substances structurally related to histamine, increased [3H]oestradiol uptake by the spayed rat uterus. The latter (an antihistamine drug acting on H2-receptors) as well as pyrathiazine (a histamine releaser having antihistamine properties) decreased the effect of histamine on oestradiol uptake whereas diphenhydramine (an antihistamine drug blocking H1-receptors) did not modify it. Pyrathiazine was itself able to diminish oestradiol uptake.", "contents": "Further evidence for histamine facilitating oestrogen action in the uterus. The effect of doses of estradiol ranging from 0-0125 to 1-6 mug on the uterine weight of the spayed rat was studied 24 h after a single s.c. injection of the hormone. The lowest dose inducing a significant increase in uterine weight was 0-32 mug. When histamine dihydrochloride (50 mg) was simultaneously injected with the hormone, the effect of small doses of oestradiol (0-0125--0-2 mug) was significantly increased. When oestradiol and histamine were administered for 3 successive days, the uterine weight of animals receiving 0-0125 mug oestradiol, if compared with untreated controls, was increased only in the histamine-treated group. When 0-05 mug oestradiol was administered histamine did not modify the increase already produced by the hormone. Spermidine and burimamide, two substances structurally related to histamine, increased [3H]oestradiol uptake by the spayed rat uterus. The latter (an antihistamine drug acting on H2-receptors) as well as pyrathiazine (a histamine releaser having antihistamine properties) decreased the effect of histamine on oestradiol uptake whereas diphenhydramine (an antihistamine drug blocking H1-receptors) did not modify it. Pyrathiazine was itself able to diminish oestradiol uptake."}
{"id": "PMID:3617", "title": "Prolactin stimulation test with perphenazine: an evaluation of plasma prolactin levels and pituitary secretory activity in the rat.", "content": "Many investigations of the regulation of prolactin synthesis and release are based on single plasma prolactin determinations. The purpose of the present experiment was to ascertain whether groups of rats (i.e. young or adult, male or female animals, being either intact, gonadectomized or gonadectomized and treated with oestrone), differing  in age and/or endocrine status, will react to a single dose of perphenazine by an acute release of pituitary prolactin in proportion to their initial plasma prolactin levels. No consistent relation existed between the classification of the twelve groups of rats into three categories of basal plasma prolactin levels (i.e. less than 20, 25-50, greater than 125 ng/ml) and their response to perphenazine. Even though all groups showed a highly significant increase of plasma prolactin levels the magnitude of the maximum prolactin response at 30 min varied greatly within the groups of one category and thus was not related to the initial prolactin levels. The effect of 14 days of oestrone treatment in increasing plasma prolactin levels in gonadectomized animals was greatest in young and adult male rats, less in young females and not significant in adult females. The results obtained after perphenazine treatment in the latter group made it clear that the effect of oestrogen treatment on prolactin release can be completely blocked by increasing synthesis and/or release of the prolactin-release inhibiting factor (PIF). Since perphenazine induces decrease of pituitary prolactin and a concomitant increase of plasma prolactin levels through lowered PIF-action, the positive effect of oestrogens on prolactin release (as observed in gonadectomized male and young female rats) apparently is caused by a different mode of action. The implications of these findings for the regulation of prolactin release, as affected by the endocrine status of the rat, is discussed. Moreover, comparison of prolactin lost from the pituitary and gained in the circulation of the experimental animals, with amounts of prolactin that were observed to disappear from plasma during the experiment, provided suggestive evidence that the capacity to synthesize and/or eliminate prolactin, after a sudden provoked release of the hormone, differed among the groups. The rates of synthesis by the pituitary, of release from the pituitary into the circulation as well as of elimination of the hormone from the circulation (equally involved in determing actual plasma levels) are thought, therefore, to be far more important for the elucidation of prolactin regulation than single plasma prolactin determinations.", "contents": "Prolactin stimulation test with perphenazine: an evaluation of plasma prolactin levels and pituitary secretory activity in the rat. Many investigations of the regulation of prolactin synthesis and release are based on single plasma prolactin determinations. The purpose of the present experiment was to ascertain whether groups of rats (i.e. young or adult, male or female animals, being either intact, gonadectomized or gonadectomized and treated with oestrone), differing  in age and/or endocrine status, will react to a single dose of perphenazine by an acute release of pituitary prolactin in proportion to their initial plasma prolactin levels. No consistent relation existed between the classification of the twelve groups of rats into three categories of basal plasma prolactin levels (i.e. less than 20, 25-50, greater than 125 ng/ml) and their response to perphenazine. Even though all groups showed a highly significant increase of plasma prolactin levels the magnitude of the maximum prolactin response at 30 min varied greatly within the groups of one category and thus was not related to the initial prolactin levels. The effect of 14 days of oestrone treatment in increasing plasma prolactin levels in gonadectomized animals was greatest in young and adult male rats, less in young females and not significant in adult females. The results obtained after perphenazine treatment in the latter group made it clear that the effect of oestrogen treatment on prolactin release can be completely blocked by increasing synthesis and/or release of the prolactin-release inhibiting factor (PIF). Since perphenazine induces decrease of pituitary prolactin and a concomitant increase of plasma prolactin levels through lowered PIF-action, the positive effect of oestrogens on prolactin release (as observed in gonadectomized male and young female rats) apparently is caused by a different mode of action. The implications of these findings for the regulation of prolactin release, as affected by the endocrine status of the rat, is discussed. Moreover, comparison of prolactin lost from the pituitary and gained in the circulation of the experimental animals, with amounts of prolactin that were observed to disappear from plasma during the experiment, provided suggestive evidence that the capacity to synthesize and/or eliminate prolactin, after a sudden provoked release of the hormone, differed among the groups. The rates of synthesis by the pituitary, of release from the pituitary into the circulation as well as of elimination of the hormone from the circulation (equally involved in determing actual plasma levels) are thought, therefore, to be far more important for the elucidation of prolactin regulation than single plasma prolactin determinations."}
{"id": "PMID:3618", "title": "Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response.", "content": "The secretion of vasoactive amines from rabbit platelets induced by the platelet-activating factor (PAF) derived from IgE-sensitized rabbit basophils, was examined. The secretion required calcium has previously been shown to be noncytotoxic and was optimal in both rate and extent at 37 degrees C and pH 7.2. Different temperature-sensitive steps were rate limiting for secretion above or below 20 degrees C. The rate of secretion was dependent upon the concentration of PAF and also of platelets. Maximal rates were observed with relatively low concentrations of platelets (2.5 X 10(8)/ml), sharply contrasting with other platelet stimuli such as C3 or thrombin. The extent of secretion was dependent upon PAF concentration until a maximum of 50 or 60% of the serotonin was released and then declined with increasing amounts of PAF. This was interpreted to result from the platelets becoming desensitized to the PAF, a process that shuts off the secretion. Such a desensitization was demonstrated and was shown to be stimulus specific, i.e., other stimuli could still induce secretion from PAF-desensitized platelets. PAF extracted with ethanol from the albumin to which it is usually bound during preparation, exhibited similar characteristics, except that secretion of up to 90% of the serotonin was induced. The extracted PAF thus seemed less able to induce the desensitization. Its use did provide important evidence that populations of rabbit platelets are relatively homogenous in their ability to respond to PAF.", "contents": "Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response. The secretion of vasoactive amines from rabbit platelets induced by the platelet-activating factor (PAF) derived from IgE-sensitized rabbit basophils, was examined. The secretion required calcium has previously been shown to be noncytotoxic and was optimal in both rate and extent at 37 degrees C and pH 7.2. Different temperature-sensitive steps were rate limiting for secretion above or below 20 degrees C. The rate of secretion was dependent upon the concentration of PAF and also of platelets. Maximal rates were observed with relatively low concentrations of platelets (2.5 X 10(8)/ml), sharply contrasting with other platelet stimuli such as C3 or thrombin. The extent of secretion was dependent upon PAF concentration until a maximum of 50 or 60% of the serotonin was released and then declined with increasing amounts of PAF. This was interpreted to result from the platelets becoming desensitized to the PAF, a process that shuts off the secretion. Such a desensitization was demonstrated and was shown to be stimulus specific, i.e., other stimuli could still induce secretion from PAF-desensitized platelets. PAF extracted with ethanol from the albumin to which it is usually bound during preparation, exhibited similar characteristics, except that secretion of up to 90% of the serotonin was induced. The extracted PAF thus seemed less able to induce the desensitization. Its use did provide important evidence that populations of rabbit platelets are relatively homogenous in their ability to respond to PAF."}
{"id": "PMID:3619", "title": "Activation of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. II. The role of serine proteases, cyclic nucleotides, and contractile elements in PAF-induced secretion.", "content": "Secretion of serotonin from platelets induced by platelet-activating factor (PAF) derived from antigen-stimulated, IgE-sensitized rabbit basophils was studied to further characterize the biochemical requirements. Inhibition of secretion with diisopropylphosphofluoridate (DFP) was observed if the DFP was present during the reaction, but not if platelets or PAF were pretreated with the inhibitor. This suggested a role for an activatable serine protease in the secretion. Supporting evidence came from the observation that other protease inhibitors and a variety of low molecular weight amino acid esters were also inhibitory. TAMe was most effective, and AGLMe and LeuMe were inactive, indicating a specificity for different esters. Secretion was reduced by agents that increased intracellular cyclic AMP (cAMP), but enhanced by alpha-adrenergic stimulation, which reduced the levels of cAMP. Concurrent with PAF-induced secretion, a reduction in cAMP levels was observed. No effect of cyclic GMP or cholinergic stimulation was found. Secretion was inhibited by colchicine and enhanced by cytochalasin B, suggesting a role for microfilaments and microtubules. The effects of these three systems on PAF-induced secretion indicate the basic uniformity of the secretory process in platelets (and other cells) whatever the stimulus. The uniqueness of the reaction apparently lies in the stimulus-receptor interaction and the nature of the serine protease which is activated.", "contents": "Activation of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. II. The role of serine proteases, cyclic nucleotides, and contractile elements in PAF-induced secretion. Secretion of serotonin from platelets induced by platelet-activating factor (PAF) derived from antigen-stimulated, IgE-sensitized rabbit basophils was studied to further characterize the biochemical requirements. Inhibition of secretion with diisopropylphosphofluoridate (DFP) was observed if the DFP was present during the reaction, but not if platelets or PAF were pretreated with the inhibitor. This suggested a role for an activatable serine protease in the secretion. Supporting evidence came from the observation that other protease inhibitors and a variety of low molecular weight amino acid esters were also inhibitory. TAMe was most effective, and AGLMe and LeuMe were inactive, indicating a specificity for different esters. Secretion was reduced by agents that increased intracellular cyclic AMP (cAMP), but enhanced by alpha-adrenergic stimulation, which reduced the levels of cAMP. Concurrent with PAF-induced secretion, a reduction in cAMP levels was observed. No effect of cyclic GMP or cholinergic stimulation was found. Secretion was inhibited by colchicine and enhanced by cytochalasin B, suggesting a role for microfilaments and microtubules. The effects of these three systems on PAF-induced secretion indicate the basic uniformity of the secretory process in platelets (and other cells) whatever the stimulus. The uniqueness of the reaction apparently lies in the stimulus-receptor interaction and the nature of the serine protease which is activated."}
{"id": "PMID:3620", "title": "Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease.", "content": "Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: \"acid\" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, alpha-arabinosidase, alpha-mannosidase, alpha-glucosidase, beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and acid phosphatase. Enzymatic activity varied greatly with cell type and the enzyme being measured; the importance of assaying pure preparations especially for heterozygote detection is emphasized. Gaucher's disease patients' cells were found to be deficient in the pH 4.0 acid beta-glucosidase, variable in the pH 5.0 beta-glucosidase, and normal in all other acid hydrolases tested, including acid phosphatase, the activity of which is known to be elevated in plasma. Blood cells of a patient with Fabry's disease were deficient in alpha-galactosidase and normal in all other acid hydrolases tested.", "contents": "Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease. Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: \"acid\" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, alpha-arabinosidase, alpha-mannosidase, alpha-glucosidase, beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and acid phosphatase. Enzymatic activity varied greatly with cell type and the enzyme being measured; the importance of assaying pure preparations especially for heterozygote detection is emphasized. Gaucher's disease patients' cells were found to be deficient in the pH 4.0 acid beta-glucosidase, variable in the pH 5.0 beta-glucosidase, and normal in all other acid hydrolases tested, including acid phosphatase, the activity of which is known to be elevated in plasma. Blood cells of a patient with Fabry's disease were deficient in alpha-galactosidase and normal in all other acid hydrolases tested."}
{"id": "PMID:3621", "title": "Regulation of the oxidative NADP-enzyme tissue levels in Drosophila melanogaster. I. Modulation by dietary carbohydrate and lipid.", "content": "Wild-type third instar larvae of Drosophilia melanogaster fed a casein-sucrose synthetic diet supplemented with phosphatidylcholine (4 mg/ml) possessed 33% more tissue lipid and a modified fatty acid profile compared to larvae fed a fat free-sucrose diet. The rates of lipid synthesis and pentose shunt activity were 2.1 and 2.2 times greater respectively in larvae fed the fat free-sucrose diet than in fat-sucrose fed animals. The tissue concentrations of acetyl-CoA and acyl-CoA were 80 and 61% higher respectively, CoA 49% lower, and the NADPH/NADP+ ratio greater in fat-sucrose fed larvae than in larvae fed a fat free-sucrose diet. Thus, larvae effectively utilized dietary lipid for lipid synthesis and as a supplementary energy source to carbohydrate.", "contents": "Regulation of the oxidative NADP-enzyme tissue levels in Drosophila melanogaster. I. Modulation by dietary carbohydrate and lipid. Wild-type third instar larvae of Drosophilia melanogaster fed a casein-sucrose synthetic diet supplemented with phosphatidylcholine (4 mg/ml) possessed 33% more tissue lipid and a modified fatty acid profile compared to larvae fed a fat free-sucrose diet. The rates of lipid synthesis and pentose shunt activity were 2.1 and 2.2 times greater respectively in larvae fed the fat free-sucrose diet than in fat-sucrose fed animals. The tissue concentrations of acetyl-CoA and acyl-CoA were 80 and 61% higher respectively, CoA 49% lower, and the NADPH/NADP+ ratio greater in fat-sucrose fed larvae than in larvae fed a fat free-sucrose diet. Thus, larvae effectively utilized dietary lipid for lipid synthesis and as a supplementary energy source to carbohydrate."}
{"id": "PMID:3622", "title": "Analysis of acetate non-utilizing (acu) mutants in Aspergillus nidulans.", "content": "Genetic analysis of 119 acetate non-utilizing (acu) mutants in Aspergillus nidulans revealed ten new loci affecting acetate metabolism in addition to the three previously recognized on the basis of resistance to fluoroacetate and acetate non-utilization. The enzyme lesions associated with mutations at seven of the acu loci are described. These are: facA (= acuA), acetyl-CoA synthase; acuD, isocitrate lyase; acuE, malate synthase; acuF, phosphoenolpyruvate carboxykinase; acuG, fructose 1,6-diphosphatase; acuK and acuM, malic enzyme. The acu loci have been mapped and are widely distributed over the genome of A. nidulans. Close linkage has only been found between acuA and acuD (less than 1% recombination). There is no evidence for any pleiotropic mutation in that region affecting the expression of both these genes. Poor induction of the enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase in mutants lacking acetyl-CoA synthase, and also in the other two classes of fluoroacetate-resistant mutants, indicates that the inducer, acetate, may be metabolized to a true metabolic inducer, perhaps acetyl-CoA, to effect formation of the enzymes. There is no evidence of any other class of pleiotropic recessive acu mutations affecting the expression of the acuD and acuE genes, which are therefore thought to be subject to negative rather than positive control.", "contents": "Analysis of acetate non-utilizing (acu) mutants in Aspergillus nidulans. Genetic analysis of 119 acetate non-utilizing (acu) mutants in Aspergillus nidulans revealed ten new loci affecting acetate metabolism in addition to the three previously recognized on the basis of resistance to fluoroacetate and acetate non-utilization. The enzyme lesions associated with mutations at seven of the acu loci are described. These are: facA (= acuA), acetyl-CoA synthase; acuD, isocitrate lyase; acuE, malate synthase; acuF, phosphoenolpyruvate carboxykinase; acuG, fructose 1,6-diphosphatase; acuK and acuM, malic enzyme. The acu loci have been mapped and are widely distributed over the genome of A. nidulans. Close linkage has only been found between acuA and acuD (less than 1% recombination). There is no evidence for any pleiotropic mutation in that region affecting the expression of both these genes. Poor induction of the enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase in mutants lacking acetyl-CoA synthase, and also in the other two classes of fluoroacetate-resistant mutants, indicates that the inducer, acetate, may be metabolized to a true metabolic inducer, perhaps acetyl-CoA, to effect formation of the enzymes. There is no evidence of any other class of pleiotropic recessive acu mutations affecting the expression of the acuD and acuE genes, which are therefore thought to be subject to negative rather than positive control."}
{"id": "PMID:3623", "title": "Predicting individual responses to drug treatment in schizophrenia: a test dose model.", "content": "The literature and the findings from the Camarillo Schizophrenia Research Project reported in this paper indicate that a satisfactory method for predicting the response of an individual schizophrenic patient to antipsychotic drugs has yet to be devised. A test dose procedure is described which offers promise of a practical approach to selecting the most appropriate drug and dosage for a particular patient and tailoring blood concentrations to the needs of the individual case. Preliminary findings indicate that the test dose procedure is feasible; that detectable changes occur after a single test dose; and that measurements made during the test dose period may be predictive of eventual outcome. These findings are, of course, only a report of a preliminary pilot experiment, subject to important caveats about small number of cases, interpretation of large numbers of correlation coefficients, and need for cross-validation. Nevertheless, they are encouraging and suggest that the test dose approach has considerable potential for further research.", "contents": "Predicting individual responses to drug treatment in schizophrenia: a test dose model. The literature and the findings from the Camarillo Schizophrenia Research Project reported in this paper indicate that a satisfactory method for predicting the response of an individual schizophrenic patient to antipsychotic drugs has yet to be devised. A test dose procedure is described which offers promise of a practical approach to selecting the most appropriate drug and dosage for a particular patient and tailoring blood concentrations to the needs of the individual case. Preliminary findings indicate that the test dose procedure is feasible; that detectable changes occur after a single test dose; and that measurements made during the test dose period may be predictive of eventual outcome. These findings are, of course, only a report of a preliminary pilot experiment, subject to important caveats about small number of cases, interpretation of large numbers of correlation coefficients, and need for cross-validation. Nevertheless, they are encouraging and suggest that the test dose approach has considerable potential for further research."}
{"id": "PMID:3624", "title": "On the bimodality of the distribution of electrodermal orienting responses in schizophrenic patients.", "content": "Data are presented from four of the author's studies on the electrodermal orienting responss which fail to confirm the findings of Gruzelier and Venables of a markedly bimodal distribution of ORs in schizophrenic populations. A review of the findings of other earlier studies, none of which confirm the bimodal hypothesis although some used patients taking phenothiazines, shows that differential effects of drugs, although probably an important factor, by itself cannot account entirely for the discrepancies in results. It is hypothesized that due to changes in hospital discharge policies, the groups of patients tested by Gruzelier and Venables, compared to those tested in earlier studies, were more heavily weighted with patients whose symptoms were resistant to phenothiazines. These patients may either have come from the extremes of the responsivity distribution or have atypical reactions to neuroleptic drugs.", "contents": "On the bimodality of the distribution of electrodermal orienting responses in schizophrenic patients. Data are presented from four of the author's studies on the electrodermal orienting responss which fail to confirm the findings of Gruzelier and Venables of a markedly bimodal distribution of ORs in schizophrenic populations. A review of the findings of other earlier studies, none of which confirm the bimodal hypothesis although some used patients taking phenothiazines, shows that differential effects of drugs, although probably an important factor, by itself cannot account entirely for the discrepancies in results. It is hypothesized that due to changes in hospital discharge policies, the groups of patients tested by Gruzelier and Venables, compared to those tested in earlier studies, were more heavily weighted with patients whose symptoms were resistant to phenothiazines. These patients may either have come from the extremes of the responsivity distribution or have atypical reactions to neuroleptic drugs."}
{"id": "PMID:3632", "title": "Sudden hemorrhage in metastatic thyroid carcinoma of the brain during treatment with iodine-131.", "content": "A patient with papillary--follicular carcinoma of the thyroid, with metastases to the lungs, skeleton, and brain was treated 5 weeks after thyroidectomy with 135 mCi of 131I. Although preliminary studies with 1 mCi had not shown any iodine uptake by the brain metastasis, this lesion showed intense concentration at the time of the larger therapeutic dose. Four days later, acute hemorrhage of the tumor occurred, requiring surgical removal. Although 131I therapy would seem an unlikely cause of acute necrosis and hemorrhage in these lesions, the association of therapeutic radioiodine and hemorrhage is interesting. Since recent reports suggest that brain metastasis may be somewhat more common than previously suspected, we suggest that brain imaging be included in the workup prior to radioiodine therapy of patients with advanced metastatic disease or neurologic symptoms.", "contents": "Sudden hemorrhage in metastatic thyroid carcinoma of the brain during treatment with iodine-131. A patient with papillary--follicular carcinoma of the thyroid, with metastases to the lungs, skeleton, and brain was treated 5 weeks after thyroidectomy with 135 mCi of 131I. Although preliminary studies with 1 mCi had not shown any iodine uptake by the brain metastasis, this lesion showed intense concentration at the time of the larger therapeutic dose. Four days later, acute hemorrhage of the tumor occurred, requiring surgical removal. Although 131I therapy would seem an unlikely cause of acute necrosis and hemorrhage in these lesions, the association of therapeutic radioiodine and hemorrhage is interesting. Since recent reports suggest that brain metastasis may be somewhat more common than previously suspected, we suggest that brain imaging be included in the workup prior to radioiodine therapy of patients with advanced metastatic disease or neurologic symptoms."}
{"id": "PMID:3635", "title": "Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis.", "content": "Concentrations of bacteria in cerebrospinal fluid ranged from 4.5 X 10(3) to 3 X 10(8) colony-forming units/ml in 27 patients with bacterial meningitis before antibiotic therapy and from 4 X 10(1) to 1.4 X 10(6) CFU/ml in four patients after one to two days of antibiotic therapy. All patients with persistent positive cultures had pretreatment concentrations of 10(7) CFU/ml or greater. A significant association was observed between cerebrospinal fluid lactic acid dehydrogenase activity and concentrations of bacteria (p less than 0.01). Large inocula of Hemophilus influenzae type b (10(7)) increased the minimal inhibitory concentration for penicillin and ampicillin but not for chloramphenicol. The minimal inhibitory concentration of each of the three antibiotics increased when group B streptococci were assayed. These data indicate that persistence of a positive culture may be related to large initial concentrations of bacteria. The relative \"resistance\" in vitro of large inocula possibly contributes to this persistence. These observations are also consistent with the hypothesis that lactic acid dehydrogenase activity in cerebrospinal fluid is derived from bacteria.", "contents": "Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis. Concentrations of bacteria in cerebrospinal fluid ranged from 4.5 X 10(3) to 3 X 10(8) colony-forming units/ml in 27 patients with bacterial meningitis before antibiotic therapy and from 4 X 10(1) to 1.4 X 10(6) CFU/ml in four patients after one to two days of antibiotic therapy. All patients with persistent positive cultures had pretreatment concentrations of 10(7) CFU/ml or greater. A significant association was observed between cerebrospinal fluid lactic acid dehydrogenase activity and concentrations of bacteria (p less than 0.01). Large inocula of Hemophilus influenzae type b (10(7)) increased the minimal inhibitory concentration for penicillin and ampicillin but not for chloramphenicol. The minimal inhibitory concentration of each of the three antibiotics increased when group B streptococci were assayed. These data indicate that persistence of a positive culture may be related to large initial concentrations of bacteria. The relative \"resistance\" in vitro of large inocula possibly contributes to this persistence. These observations are also consistent with the hypothesis that lactic acid dehydrogenase activity in cerebrospinal fluid is derived from bacteria."}
{"id": "PMID:3638", "title": "Quantitative determination of resorcinol in presence of phenol.", "content": "A simple and accurate method for the quantitative determination of resorcinol in the presence of phenol is reported. The method is based on the formation of indophenol by reacting resorcinol with 2, 6-dibromoquinone-4-chlorimide. The concentration of indophenol can be measured spectrophotometrically. This method is recommended for the determination of resorcinol in resorcinol-phenol-boric acid solution and carbol-fuchsin solution. The decomposition products of resorcinol and phenol, e.g., colored quinones, do not interfere with the assay procedure.", "contents": "Quantitative determination of resorcinol in presence of phenol. A simple and accurate method for the quantitative determination of resorcinol in the presence of phenol is reported. The method is based on the formation of indophenol by reacting resorcinol with 2, 6-dibromoquinone-4-chlorimide. The concentration of indophenol can be measured spectrophotometrically. This method is recommended for the determination of resorcinol in resorcinol-phenol-boric acid solution and carbol-fuchsin solution. The decomposition products of resorcinol and phenol, e.g., colored quinones, do not interfere with the assay procedure."}
{"id": "PMID:3639", "title": "Oil-water distribution of p-alkylpyridines.", "content": "The distribution of a homologous series of p-alkylpyridines between water and six organic solvents with varying degrees of polarity was investigated. The distribution coefficients were considered as reflections of the strength of net interactions involved in the solvents. The order was chloroform greater than octanol greater than carbon tetrachloride greater than butyl ether greater than hexadecane greater than octane. The effect of the methylene group upon the distribution coefficients differed little among the six solvents. The relative constancy was attributed to the predominance of the dispersion forces in the incremental effect.", "contents": "Oil-water distribution of p-alkylpyridines. The distribution of a homologous series of p-alkylpyridines between water and six organic solvents with varying degrees of polarity was investigated. The distribution coefficients were considered as reflections of the strength of net interactions involved in the solvents. The order was chloroform greater than octanol greater than carbon tetrachloride greater than butyl ether greater than hexadecane greater than octane. The effect of the methylene group upon the distribution coefficients differed little among the six solvents. The relative constancy was attributed to the predominance of the dispersion forces in the incremental effect."}
{"id": "PMID:3640", "title": "Neurogenic influences of bilateral adrenalectomy on monoamine oxidase.", "content": "Bilateral adrenalectomy (10 days) increased the monoamine oxidase activity of the rat heart, vas deferens, spleen, superior cervical ganglion, and hypothalamus but not that of the rest of the brain, kidney, and liver. Experiments were made to determine whether the increased activity was due to neurogenic influences and whether the enhanced activity of monoamine oxidase was intra- or extraneuronally located. Ganglionic blockade with chlorisondamine failed to alter the rise in cardiac monoamine oxidase. Likewise, superior cervical ganglion monoamine oxidase was unaffected by surgical denervation. 6-Hydroxydopamine abolished the increase in monoamine oxidase activity of the vas deferens, spleen, and superior cervical ganglion but failed to alter that of the kidney, hypothalamus, and the rest of the brain. Cardiac monoamine oxidase was reduced markedly by 6-hydroxydopamine, but the remaining activity was still significantly elevated over the respective control values. The data suggest that the increase in organ monoamine oxidase is predominantly of neuronal origin and that this increase is not due to transsynaptic induction.", "contents": "Neurogenic influences of bilateral adrenalectomy on monoamine oxidase. Bilateral adrenalectomy (10 days) increased the monoamine oxidase activity of the rat heart, vas deferens, spleen, superior cervical ganglion, and hypothalamus but not that of the rest of the brain, kidney, and liver. Experiments were made to determine whether the increased activity was due to neurogenic influences and whether the enhanced activity of monoamine oxidase was intra- or extraneuronally located. Ganglionic blockade with chlorisondamine failed to alter the rise in cardiac monoamine oxidase. Likewise, superior cervical ganglion monoamine oxidase was unaffected by surgical denervation. 6-Hydroxydopamine abolished the increase in monoamine oxidase activity of the vas deferens, spleen, and superior cervical ganglion but failed to alter that of the kidney, hypothalamus, and the rest of the brain. Cardiac monoamine oxidase was reduced markedly by 6-hydroxydopamine, but the remaining activity was still significantly elevated over the respective control values. The data suggest that the increase in organ monoamine oxidase is predominantly of neuronal origin and that this increase is not due to transsynaptic induction."}
{"id": "PMID:3641", "title": "Binding study of tetracyclines to human serum albumin using difference spectrophotometry.", "content": "The binding of several tetracyclines to human serum albumin was studied using difference spectrophotometry and a spectrophotometric probe, 2-(4'-hydroxybenzeneazo)benzoic acid. Difference spectra observed for the interaction between the probe and human serum albumin were similar to probe-bovine serum albumin spectra but were less intense for a given concentration of probe and did not reach saturation as quickly. Difference spectra for the tetracyclines were dependent on the characteristics of the ring substituents. More hydrophobic substituents on the D and C rings tended to give more intense difference spectra, but charge-transfer complexing may also have been involved since methacycline with a methylene group in the 6-position showed the most intense spectra of the compounds studied. Solvent perturbation, pH, and urea studies tended to confirm that something other than hydrophobic binding of the tetracyclines was involved. Drug-probe displacement studies showed that methacycline gave the greatest probe displacement followed by doxycycline, chlortetracycline, oxytetracycline, and tetracycline. This order of displacement of the anionic probe indicates that both hydrophobic and charge-transfer binding are involved. Experiments with calcium ion and ethylenediaminetetraacetic acid showed that the difference spectra obtained with the tetracyclines and human serum albumin were not the result of metallic bridge-chelate formation.", "contents": "Binding study of tetracyclines to human serum albumin using difference spectrophotometry. The binding of several tetracyclines to human serum albumin was studied using difference spectrophotometry and a spectrophotometric probe, 2-(4'-hydroxybenzeneazo)benzoic acid. Difference spectra observed for the interaction between the probe and human serum albumin were similar to probe-bovine serum albumin spectra but were less intense for a given concentration of probe and did not reach saturation as quickly. Difference spectra for the tetracyclines were dependent on the characteristics of the ring substituents. More hydrophobic substituents on the D and C rings tended to give more intense difference spectra, but charge-transfer complexing may also have been involved since methacycline with a methylene group in the 6-position showed the most intense spectra of the compounds studied. Solvent perturbation, pH, and urea studies tended to confirm that something other than hydrophobic binding of the tetracyclines was involved. Drug-probe displacement studies showed that methacycline gave the greatest probe displacement followed by doxycycline, chlortetracycline, oxytetracycline, and tetracycline. This order of displacement of the anionic probe indicates that both hydrophobic and charge-transfer binding are involved. Experiments with calcium ion and ethylenediaminetetraacetic acid showed that the difference spectra obtained with the tetracyclines and human serum albumin were not the result of metallic bridge-chelate formation."}
{"id": "PMID:3642", "title": "Fluorescence of hydralazine in concentrated sulfuric acid.", "content": "Hydralazine shows intense fluorescence at 353 nm in concentrated sulfuric acid when excited at 320 nm. This fluorescence can be utilized for the quantitative analysis of the drug in dosage forms.", "contents": "Fluorescence of hydralazine in concentrated sulfuric acid. Hydralazine shows intense fluorescence at 353 nm in concentrated sulfuric acid when excited at 320 nm. This fluorescence can be utilized for the quantitative analysis of the drug in dosage forms."}
{"id": "PMID:3643", "title": "The antiarrhythmic and cardiovascular properties of 1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride, UM-424.", "content": "The quarternary ammonium compound, UM-424 [1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride], was evaluated for its antiarrhythmic and hemodynamic effects. UM-424 converted ouabain-induced ventricular tachycardia in the anesthetized dog when administered in an average dose of 4.6 mg/kg i.v. Pretreatment of anesthetized dogs with UM-424, 10 mg/kg, provided complete protection against the development of premature beats and ventricular fibrillation when the left anterior descending coronary artery was occluded for 20 minutes and then released. UM-424 was effective in reversing ventricular arrhythmias in conscious animals which had been subjected to a two-stage ligation of the anterior descending coronary artery. The mean ectopic rate in a group of five dogs was 143 +/- 4.0 (S.E.M.) beats/min 24 hours after coronary ligation. Normal sinus rhythm was restored with a mean dose of 9.5 mg/kg of UM-424 and was maintained for a period in excess of 60 minutes. The ventricular fibrillation threshold was increased from a control value of 4.0 +/- 0.4 to 26.2 +/- 8.6 mA (P less than .05) 30 minutes after pretreatment with UM-424, 10 mg/kg. Inotropic and chronotropic dose-response studies to isoproterenol in the anesthetized dog demonstrated that the quarternary compound lacked beta adrenergic receptor blocking properties. UM-424, 10 mg/kg, did not produce any persistent changes in spontaneous heart rate, cardiac contractile force, left ventricular dP/ct, mean arterial blood pressure, cardiac output and mean pulmonary arterial pressure.", "contents": "The antiarrhythmic and cardiovascular properties of 1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride, UM-424. The quarternary ammonium compound, UM-424 [1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride], was evaluated for its antiarrhythmic and hemodynamic effects. UM-424 converted ouabain-induced ventricular tachycardia in the anesthetized dog when administered in an average dose of 4.6 mg/kg i.v. Pretreatment of anesthetized dogs with UM-424, 10 mg/kg, provided complete protection against the development of premature beats and ventricular fibrillation when the left anterior descending coronary artery was occluded for 20 minutes and then released. UM-424 was effective in reversing ventricular arrhythmias in conscious animals which had been subjected to a two-stage ligation of the anterior descending coronary artery. The mean ectopic rate in a group of five dogs was 143 +/- 4.0 (S.E.M.) beats/min 24 hours after coronary ligation. Normal sinus rhythm was restored with a mean dose of 9.5 mg/kg of UM-424 and was maintained for a period in excess of 60 minutes. The ventricular fibrillation threshold was increased from a control value of 4.0 +/- 0.4 to 26.2 +/- 8.6 mA (P less than .05) 30 minutes after pretreatment with UM-424, 10 mg/kg. Inotropic and chronotropic dose-response studies to isoproterenol in the anesthetized dog demonstrated that the quarternary compound lacked beta adrenergic receptor blocking properties. UM-424, 10 mg/kg, did not produce any persistent changes in spontaneous heart rate, cardiac contractile force, left ventricular dP/ct, mean arterial blood pressure, cardiac output and mean pulmonary arterial pressure."}
{"id": "PMID:3644", "title": "Acid secretion by guinea-pig isolated stomach.", "content": "An isolated stomach preparation from the guinea-pig is described. 2. Both histamine acid phosphate (1-4 mug/ml.) and theophylline hydrate (0-2-3-2 mg/ml.) separately stimulated hydrochloric acid, HCl, secretion from the guinea-pig stomach preparation. A linear dose-response relationship was obtained for theophylline. 3. Addition of theophylline (0-2 and 1-6 mg/ml.) during maximal response to histamine increased the secretion further, whereas addition of histamine during maximal response to theophylline did not cause further secretion. 4. The secretory activities of Nalpha-MeH (0-3-5-0 muM), Nalpha-Me2H (1-2-9-5 muM) and 5-MeH (1-5-12 muM) were compared with histamine (0-9-13 muM) on a threshold background secretion induced by theophylline (0-2 mg/ml.). Linear log.-dose response relationships were obtained for each test drug. The results confirm that Nalpha-MeH is a more potent secretagogue than histamine. 5. Pentagastrin (0-3-1-0 mug/ml.) stimulated HCl secretion in approximately half the experiments. The response was often transitory. In the other experiments, pentagastrin had no effect on HCl secretion although subsequent administration of histamine did stimulate HCl secretion.", "contents": "Acid secretion by guinea-pig isolated stomach. An isolated stomach preparation from the guinea-pig is described. 2. Both histamine acid phosphate (1-4 mug/ml.) and theophylline hydrate (0-2-3-2 mg/ml.) separately stimulated hydrochloric acid, HCl, secretion from the guinea-pig stomach preparation. A linear dose-response relationship was obtained for theophylline. 3. Addition of theophylline (0-2 and 1-6 mg/ml.) during maximal response to histamine increased the secretion further, whereas addition of histamine during maximal response to theophylline did not cause further secretion. 4. The secretory activities of Nalpha-MeH (0-3-5-0 muM), Nalpha-Me2H (1-2-9-5 muM) and 5-MeH (1-5-12 muM) were compared with histamine (0-9-13 muM) on a threshold background secretion induced by theophylline (0-2 mg/ml.). Linear log.-dose response relationships were obtained for each test drug. The results confirm that Nalpha-MeH is a more potent secretagogue than histamine. 5. Pentagastrin (0-3-1-0 mug/ml.) stimulated HCl secretion in approximately half the experiments. The response was often transitory. In the other experiments, pentagastrin had no effect on HCl secretion although subsequent administration of histamine did stimulate HCl secretion."}
{"id": "PMID:3645", "title": "Two components of the calcium current in the egg cell membrane of the tunicate.", "content": "The Ca current of the egg cell membrane of a certain tunicate, Halocynthia roretzi Drasche, was studied by the voltage-clamp technique. 2. The Ca current in the standard artificial sea water (ASW) was produced at the critical membrane potential of -10 mV after inactivating the Na current by conditioning depolarization, -30 to -15 mV. The Ca current was abolished by replacing Ca in ASW with Mg2+ or Mn2+. The Ca current was not significantly influenced by replacing Na in ASW with choline or Cs. 3. The relation of Ca current to the external Ca concentration was a monotonously increasing function, but was not linear. The current tended to saturate above 50 mM-Ca. In 100 mM-Ca ASW, the maximum peak inward current of Ca ranged from 1 to 7 X 10(-9) A. 4. The kinetics of Ca current was accurately analysed because of the small contribution of K outward current and was found to be relatively slow in comparison with the Na current. The peak time and the half-decay time of the maximum Ca current at about 25 mV were about 25 and 100 msec respectively in 100 mM-Ca ASW at 15 degrees C. 5. Addition of 20 mM-Co2+ to 100 mM-Ca ASW reduced Ca current to one fourth and 1 mM-La3+ to 100 mM-Ca ASW abolished the current. 6. Sr and Ba could substitute for Ca in Ca channels. The selectivity ratios for the 'Ca channels's were Ca (1-00):Sr(1-17):Ba(0-71) at a potential level of +40 mV. The Ca current in the egg cell membrane appeared to be essentially the same as the Ca current in the common excitable membranes, such as the crustacean muscle fibre. 7. The polyvalent cations including Ca ion and monovalent H+ ion showed the stabilizing effect upon both Na and Ca currents, by shifting V-I relations along the voltage axis. From the prediction of a theory of the diffuse double layer, the shift in the V-I relation induced by those cations should be directly related to their binding powers to the membrane. Thus, the sequence of the binding powers was inferred as H+ greater than La3+ greater than Co2+ greater than Mn2+ greater than Ca2+ greater than Sr2+ larger than or equal to Ba2+ greater than Mg2+. 9. In Na-free ASW, such as isotonic Ca ASW, Ca current was composed of two components. The one component was the Ca current described in 1 to 6. The other was also dependent upon the external Ca concentration, but showed the more negative critical membrane potential and the faster kinetics. It was concluded that this component should be the Ca current through Na channels. 10. The selectivity among Ca, Sr and Ba for 'Ca' current through 'Na channels' was significantly different from that of 'Ca' current through 'Ca channels', being Ca greater than Sr larger than or equal to Ba = 0.", "contents": "Two components of the calcium current in the egg cell membrane of the tunicate. The Ca current of the egg cell membrane of a certain tunicate, Halocynthia roretzi Drasche, was studied by the voltage-clamp technique. 2. The Ca current in the standard artificial sea water (ASW) was produced at the critical membrane potential of -10 mV after inactivating the Na current by conditioning depolarization, -30 to -15 mV. The Ca current was abolished by replacing Ca in ASW with Mg2+ or Mn2+. The Ca current was not significantly influenced by replacing Na in ASW with choline or Cs. 3. The relation of Ca current to the external Ca concentration was a monotonously increasing function, but was not linear. The current tended to saturate above 50 mM-Ca. In 100 mM-Ca ASW, the maximum peak inward current of Ca ranged from 1 to 7 X 10(-9) A. 4. The kinetics of Ca current was accurately analysed because of the small contribution of K outward current and was found to be relatively slow in comparison with the Na current. The peak time and the half-decay time of the maximum Ca current at about 25 mV were about 25 and 100 msec respectively in 100 mM-Ca ASW at 15 degrees C. 5. Addition of 20 mM-Co2+ to 100 mM-Ca ASW reduced Ca current to one fourth and 1 mM-La3+ to 100 mM-Ca ASW abolished the current. 6. Sr and Ba could substitute for Ca in Ca channels. The selectivity ratios for the 'Ca channels's were Ca (1-00):Sr(1-17):Ba(0-71) at a potential level of +40 mV. The Ca current in the egg cell membrane appeared to be essentially the same as the Ca current in the common excitable membranes, such as the crustacean muscle fibre. 7. The polyvalent cations including Ca ion and monovalent H+ ion showed the stabilizing effect upon both Na and Ca currents, by shifting V-I relations along the voltage axis. From the prediction of a theory of the diffuse double layer, the shift in the V-I relation induced by those cations should be directly related to their binding powers to the membrane. Thus, the sequence of the binding powers was inferred as H+ greater than La3+ greater than Co2+ greater than Mn2+ greater than Ca2+ greater than Sr2+ larger than or equal to Ba2+ greater than Mg2+. 9. In Na-free ASW, such as isotonic Ca ASW, Ca current was composed of two components. The one component was the Ca current described in 1 to 6. The other was also dependent upon the external Ca concentration, but showed the more negative critical membrane potential and the faster kinetics. It was concluded that this component should be the Ca current through Na channels. 10. The selectivity among Ca, Sr and Ba for 'Ca' current through 'Na channels' was significantly different from that of 'Ca' current through 'Ca channels', being Ca greater than Sr larger than or equal to Ba = 0."}
{"id": "PMID:3646", "title": "Oestrogenic sensitivity of rat uterine secretion.", "content": "Ovariectomized adult rats with closed uteri were treated for 7 days with different oral and s..c. doses of oestradiol, oestrone, oestriol and ethinyl oestradiol. All treatments elicited the production of uterine fluid and the potencies of oestrogens were related to the amount of fluid secreted. Ethinyl oestradiol and oestradiol displayed similar activity when given s.c. A daily dose of 0-003 mg oestradiol/kg resulted in about 700 mg fluid. Oestrone was 3-10 times and oestriol about 100 times less active. Orally, ethinyl oestradiol was the most potent substance and 700 mg secretion was obtained with a dose of 0-03 mg/kg daily. Oestradiol was about 30 times, oestrone about 100 times and oestriol 50 times less active than ethinyl oestradiol by this route. The viscosity of the secretion was unaffected, remaining between 1-6 and 2-4 cP. The pH of the fluid did not change, but that of the uterine lumen diminished slightly. These effects of oestrogens were associated with an increase in the weight of the empty uterus and a decrease in body weight.", "contents": "Oestrogenic sensitivity of rat uterine secretion. Ovariectomized adult rats with closed uteri were treated for 7 days with different oral and s..c. doses of oestradiol, oestrone, oestriol and ethinyl oestradiol. All treatments elicited the production of uterine fluid and the potencies of oestrogens were related to the amount of fluid secreted. Ethinyl oestradiol and oestradiol displayed similar activity when given s.c. A daily dose of 0-003 mg oestradiol/kg resulted in about 700 mg fluid. Oestrone was 3-10 times and oestriol about 100 times less active. Orally, ethinyl oestradiol was the most potent substance and 700 mg secretion was obtained with a dose of 0-03 mg/kg daily. Oestradiol was about 30 times, oestrone about 100 times and oestriol 50 times less active than ethinyl oestradiol by this route. The viscosity of the secretion was unaffected, remaining between 1-6 and 2-4 cP. The pH of the fluid did not change, but that of the uterine lumen diminished slightly. These effects of oestrogens were associated with an increase in the weight of the empty uterus and a decrease in body weight."}
{"id": "PMID:3647", "title": "A new series of cardioselective adrenergic beta-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols.", "content": "A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor.", "contents": "A new series of cardioselective adrenergic beta-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols. A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor."}
{"id": "PMID:3648", "title": "Teaching interviewing for pediatrics.", "content": "This paper describes a structured course for teaching interviewing which focuses on the interaction between the patient and the practitioner. Three main areas of learning were selected because of their universal application: relationship, communication, and feelings. Theoretical material is related to positive and negative interactions with patients, and these are described behaviorally in a checklist form. The development of good interviewing techniques consists of increasing the positive interactions and learning to use them as diagnostic and therapeutic tools. Different methods are utilized to help students apply these skills in clinical situations. Although this course was developed for a specific group of pediatric practitioners, it can be utilized by all types of health care professionals.", "contents": "Teaching interviewing for pediatrics. This paper describes a structured course for teaching interviewing which focuses on the interaction between the patient and the practitioner. Three main areas of learning were selected because of their universal application: relationship, communication, and feelings. Theoretical material is related to positive and negative interactions with patients, and these are described behaviorally in a checklist form. The development of good interviewing techniques consists of increasing the positive interactions and learning to use them as diagnostic and therapeutic tools. Different methods are utilized to help students apply these skills in clinical situations. Although this course was developed for a specific group of pediatric practitioners, it can be utilized by all types of health care professionals."}
{"id": "PMID:3652", "title": "Effect of calcium on the membrane potential of Amphiuma red cells.", "content": "An increase in extracellular Ca concentration causes the membrane of giant red cells of the salamander, Amphiuma means, to undergo a marked, transient hyperpolarization. This hyperpolarization is caused by an increase in K permeability of the membrane as judged from the K sensitivity of the membrane potential and from the rate of K loss under influence of raised extracellular Ca concentration. At constant external pH, the induction of hyperpolarization by increased extracellular Ca has a relatively well-defined threshold concentration. Furthermore the phenomenon is of an \"all or none\" type with most of the cells having membrane potential values either in the normal range (about -15 mV) or in the range -40 to -70mV. Shortly after suspension in Ringer's with 15 mm Ca, most if not all of the individual cells are hyperpolarized. Upon continued exposure (5-20 min) to the higher Ca concentration the membrane potential returns to the normal value in a fashion compatible with an \"all or none\" response. The observed Ca effect is sensitive to the pH of the suspending medium. At pH 6.2 the response is absent whereas the hyperpolarization is markedly stronger at pH 8.2 than at PH 7.2. It is argued that a reliable transport number for K under influence of Ca cannot be estimated from the slope of membrane potential vs. log (extracellular K concentration). This is probably related to the fact that the membrane potentials of the cells in the population do not stay constant in time. The above phenomenon is compared with the Ca-induced K permeability in poisoned human red cells or red cell ghosts. It is important to note that the cells employed in the present study are neither poisoned nor mechanically disrupted. This study emphasizes that the role of Ca in regulating cell membrane permeability to K seems to be a general feature.", "contents": "Effect of calcium on the membrane potential of Amphiuma red cells. An increase in extracellular Ca concentration causes the membrane of giant red cells of the salamander, Amphiuma means, to undergo a marked, transient hyperpolarization. This hyperpolarization is caused by an increase in K permeability of the membrane as judged from the K sensitivity of the membrane potential and from the rate of K loss under influence of raised extracellular Ca concentration. At constant external pH, the induction of hyperpolarization by increased extracellular Ca has a relatively well-defined threshold concentration. Furthermore the phenomenon is of an \"all or none\" type with most of the cells having membrane potential values either in the normal range (about -15 mV) or in the range -40 to -70mV. Shortly after suspension in Ringer's with 15 mm Ca, most if not all of the individual cells are hyperpolarized. Upon continued exposure (5-20 min) to the higher Ca concentration the membrane potential returns to the normal value in a fashion compatible with an \"all or none\" response. The observed Ca effect is sensitive to the pH of the suspending medium. At pH 6.2 the response is absent whereas the hyperpolarization is markedly stronger at pH 8.2 than at PH 7.2. It is argued that a reliable transport number for K under influence of Ca cannot be estimated from the slope of membrane potential vs. log (extracellular K concentration). This is probably related to the fact that the membrane potentials of the cells in the population do not stay constant in time. The above phenomenon is compared with the Ca-induced K permeability in poisoned human red cells or red cell ghosts. It is important to note that the cells employed in the present study are neither poisoned nor mechanically disrupted. This study emphasizes that the role of Ca in regulating cell membrane permeability to K seems to be a general feature."}
{"id": "PMID:3653", "title": "Transitory postnatal hemolysis of calf red cells by amino acids.", "content": "Among the amino acids which can be solubilized to give a concentration of 300 mm at near physiological pH, histidine and proline caused a complete hemolysis of newborn calf but not of adult cow red cells within 20 to 30 minutes at 38 degrees C. While hydroxyproline, valine, and serine resulted in a partial lysis of calf cells, threonine, glutamine, and glycine were ineffective. In this communication, emphasis has been focused on the mode of the lytic process by histidine which was found to be affected by several governing parameters including the pH, temperature and the extracellular salts in the solution. Unlike human red cells suspended in isotonic histidine, both calf and cow cells lost little Na and K ions. In the presence of 300 mm histidine, both calf and cow cells displayed an instantaneous uptake of histidine amounting to 20 to 45 mumoles/ml RBC followed by a slow influx rate of 0.25 to 0.5 mumoles/ml RBC X min. The extent to which histidine entry was allowed by the cell was counterbalanced by Cl- efflux, resulting in little change in cell volume prior to hemolysis. Moreover, histidine-induced hemolysis can be prevented by 1 mm or lower PCMBS without a discernible effect on histidine influx suggesting a possible membrane lesion or damage at the outer surface of the cell. Hemolysis induced by histidine decreased substantially when a calf reached two months of age at which time the red cells containing the fetal hemoglobin are virtually depleted. The results of hemoglobin electrophoresis obtained during this postnatal period revealed that those cells resistant to histidine hemolysis almost invariably contain the adult type hemoglobin suggesting a selective, specific action of the amino acids on the fetal cells.", "contents": "Transitory postnatal hemolysis of calf red cells by amino acids. Among the amino acids which can be solubilized to give a concentration of 300 mm at near physiological pH, histidine and proline caused a complete hemolysis of newborn calf but not of adult cow red cells within 20 to 30 minutes at 38 degrees C. While hydroxyproline, valine, and serine resulted in a partial lysis of calf cells, threonine, glutamine, and glycine were ineffective. In this communication, emphasis has been focused on the mode of the lytic process by histidine which was found to be affected by several governing parameters including the pH, temperature and the extracellular salts in the solution. Unlike human red cells suspended in isotonic histidine, both calf and cow cells lost little Na and K ions. In the presence of 300 mm histidine, both calf and cow cells displayed an instantaneous uptake of histidine amounting to 20 to 45 mumoles/ml RBC followed by a slow influx rate of 0.25 to 0.5 mumoles/ml RBC X min. The extent to which histidine entry was allowed by the cell was counterbalanced by Cl- efflux, resulting in little change in cell volume prior to hemolysis. Moreover, histidine-induced hemolysis can be prevented by 1 mm or lower PCMBS without a discernible effect on histidine influx suggesting a possible membrane lesion or damage at the outer surface of the cell. Hemolysis induced by histidine decreased substantially when a calf reached two months of age at which time the red cells containing the fetal hemoglobin are virtually depleted. The results of hemoglobin electrophoresis obtained during this postnatal period revealed that those cells resistant to histidine hemolysis almost invariably contain the adult type hemoglobin suggesting a selective, specific action of the amino acids on the fetal cells."}
{"id": "PMID:3650", "title": "ATP synthesis driven by a protonmotive force in Streptococcus lactis.", "content": "An electrochemical potential difference for hydrogen ions ( a protonmotive force) was artifically imposed across the membrane of the anaerobic bacterium Streptococcus lactis. When cells were exposed to the ionophore, valinomycin, the electrical gradient was established by a potassium diffusion potential. A chemical gradient of protons was established by manipulating the transmembrane pH gradient. When the protonmotive force attained a value of 215 mV or greater, net ATP synthesis was catalyzed by the membrane-bound Ca++, Mg++ -stimulated ATPase. This was true whether the protonmotive force was dominated by the membrane potential (negative inside) or the pH gradient (alkaline inside). Under these conditions, ATP synthesis could be blocked by the ATPase inhibitor, dicyclohexylcarbodiimide, or by ionophores which rendered the membrane specifically permeable to protons. These observations provide strong evidence in support of the chemiosmotic hypothesis, which states that the membrane-bound ATPase couples the inward movement of protons to the synthesis of ATP.", "contents": "ATP synthesis driven by a protonmotive force in Streptococcus lactis. An electrochemical potential difference for hydrogen ions ( a protonmotive force) was artifically imposed across the membrane of the anaerobic bacterium Streptococcus lactis. When cells were exposed to the ionophore, valinomycin, the electrical gradient was established by a potassium diffusion potential. A chemical gradient of protons was established by manipulating the transmembrane pH gradient. When the protonmotive force attained a value of 215 mV or greater, net ATP synthesis was catalyzed by the membrane-bound Ca++, Mg++ -stimulated ATPase. This was true whether the protonmotive force was dominated by the membrane potential (negative inside) or the pH gradient (alkaline inside). Under these conditions, ATP synthesis could be blocked by the ATPase inhibitor, dicyclohexylcarbodiimide, or by ionophores which rendered the membrane specifically permeable to protons. These observations provide strong evidence in support of the chemiosmotic hypothesis, which states that the membrane-bound ATPase couples the inward movement of protons to the synthesis of ATP."}
{"id": "PMID:3651", "title": "Effect of local anesthetics on chloride transport in erythrocytes.", "content": "The self-exchange of chloride isotopes across the human erythrocyte membrane was inhibited by tetracaine, benzocaine, and lidocaine. The inhibition by tetracaine was increased at higher pH values, but was not exclusively due to the uncharged form of tetracaine. The inhibition was effective within 5 seconds, was reversible, was non competitive with chloride ions, and was not reversed by calcium ions. These findings indicate that local anesthetics react with the erythrocyte chloride carrier at a site separate from the chloride site and cause inhibition of anion transport by a specific mechanism not involving changes in the surface charge density on the erythrocyte membrane.", "contents": "Effect of local anesthetics on chloride transport in erythrocytes. The self-exchange of chloride isotopes across the human erythrocyte membrane was inhibited by tetracaine, benzocaine, and lidocaine. The inhibition by tetracaine was increased at higher pH values, but was not exclusively due to the uncharged form of tetracaine. The inhibition was effective within 5 seconds, was reversible, was non competitive with chloride ions, and was not reversed by calcium ions. These findings indicate that local anesthetics react with the erythrocyte chloride carrier at a site separate from the chloride site and cause inhibition of anion transport by a specific mechanism not involving changes in the surface charge density on the erythrocyte membrane."}
{"id": "PMID:3660", "title": "Biochemical properties of cyclic nucleotide phosphodiesterase in metastasizing and nonmetastasizing rat mammary carcinomas.", "content": "The biochemical properties of cyclic nucleotide phosphodiesterases in a nonmetastasizing and a spontaneously metastasizing rat mammary carcinoma were compared. The phosphooiesterases in both tumors had a pH optimum of around 8.0 and preferentially hydrolysed cyclic purine nucleotides. The rate of hydrolysis of purine nucleotides in the nonmetastasizing tumor was two times higher than in the metastasizing tumor, but the rate of pyrimidine nucleotide hydrolysis was equal in both tumors. Theophylline, caffeine, and D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro20-1724) inhibited the enzyme activity in both tumors; the percent inhibition was the same by each inhibitor. The cyclic nucleotie phosphodiesterase activity in either tumor was stimulated by Mg++, Mn++, and Co++ and suppressed by Ca++, Zn,++, and Ni++. EDTA inhibited the activity below the basal level (activity in the absence of added cation), an this inhibition could be recovered up to the basal level by an equimolar quantity of either Mn++ or Mg++. Further stimulation of the enzyme activity with increasing concentrations of divalent cations was observed only with Mn++. Similar effects were observe with ethylene glycol bis(beta-aminoethyl ether)-tn,n-tetraacetic acid. The stimulatory cations affected both the low and high Michaelis constant (tkm) enzymes in these tumors by increasing the maximum velocity. In the low Km enzyme, the Km was also slightly increased. Neither guanosine 3',5'-cyclic monophosphate nor adenosine 3',5'-cyclic monophosphate had any effect on the hydrolysis of the other at physiologic levels.", "contents": "Biochemical properties of cyclic nucleotide phosphodiesterase in metastasizing and nonmetastasizing rat mammary carcinomas. The biochemical properties of cyclic nucleotide phosphodiesterases in a nonmetastasizing and a spontaneously metastasizing rat mammary carcinoma were compared. The phosphooiesterases in both tumors had a pH optimum of around 8.0 and preferentially hydrolysed cyclic purine nucleotides. The rate of hydrolysis of purine nucleotides in the nonmetastasizing tumor was two times higher than in the metastasizing tumor, but the rate of pyrimidine nucleotide hydrolysis was equal in both tumors. Theophylline, caffeine, and D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro20-1724) inhibited the enzyme activity in both tumors; the percent inhibition was the same by each inhibitor. The cyclic nucleotie phosphodiesterase activity in either tumor was stimulated by Mg++, Mn++, and Co++ and suppressed by Ca++, Zn,++, and Ni++. EDTA inhibited the activity below the basal level (activity in the absence of added cation), an this inhibition could be recovered up to the basal level by an equimolar quantity of either Mn++ or Mg++. Further stimulation of the enzyme activity with increasing concentrations of divalent cations was observed only with Mn++. Similar effects were observe with ethylene glycol bis(beta-aminoethyl ether)-tn,n-tetraacetic acid. The stimulatory cations affected both the low and high Michaelis constant (tkm) enzymes in these tumors by increasing the maximum velocity. In the low Km enzyme, the Km was also slightly increased. Neither guanosine 3',5'-cyclic monophosphate nor adenosine 3',5'-cyclic monophosphate had any effect on the hydrolysis of the other at physiologic levels."}
{"id": "PMID:3661", "title": "Hybrid-versus-parental strain reaction. III. Comparative mortality in parental strain mice of the H-2k genotype.", "content": "Lethally irradiated parental strain male and female mice were inoculated with marrow from reciprocal hybrid donors of the same sex. Hybrid cells homozygous for the H-2k genotype could recognize the quantitatively greater antigenicity of the parental strain CBA male recipients only. The more severe reaction occurred when the maternal strain of the hybrid donor was allogeneic to the recipient, which indicates the maternal effect on the antigen recognition system. This demonstration of a maternal influence on the expression of paternally derived tissue antigens made it possible to attribute the secondary disease syndrome to a hybrid-versus-parental strain reaction. The apparent differences in mortality between male and female recipients could not be attributable to X or Y chromosome disparity without additional transfers of appropriate marrow from males to females and females to males. In all cases, the parental strain-versus-hybrid reaction resulted in greater mortality than that observed in the hybrid-versus-parental strain reaction.", "contents": "Hybrid-versus-parental strain reaction. III. Comparative mortality in parental strain mice of the H-2k genotype. Lethally irradiated parental strain male and female mice were inoculated with marrow from reciprocal hybrid donors of the same sex. Hybrid cells homozygous for the H-2k genotype could recognize the quantitatively greater antigenicity of the parental strain CBA male recipients only. The more severe reaction occurred when the maternal strain of the hybrid donor was allogeneic to the recipient, which indicates the maternal effect on the antigen recognition system. This demonstration of a maternal influence on the expression of paternally derived tissue antigens made it possible to attribute the secondary disease syndrome to a hybrid-versus-parental strain reaction. The apparent differences in mortality between male and female recipients could not be attributable to X or Y chromosome disparity without additional transfers of appropriate marrow from males to females and females to males. In all cases, the parental strain-versus-hybrid reaction resulted in greater mortality than that observed in the hybrid-versus-parental strain reaction."}
{"id": "PMID:3662", "title": "Cryptorchidism, hernia, and cancer of the testis.", "content": "Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia.", "contents": "Cryptorchidism, hernia, and cancer of the testis. Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia."}
{"id": "PMID:3664", "title": "Hemodynamic and respiratory responses of conscious swine to E. coli endotoxin.", "content": "The injection of a sublethal bolus of E. coli into conscious swine produces an early increase in PAP and a decrease in LAP. This hemodynamic effect may be secondary to the pulmonary venous constriction seen in other species, or may relate to demonstrated multiple pulmonary microemboli. Hypoxemia developed in only four of 17 animals although all endotoxin-treated swine showed interstitial edema and elevated wet/dry weight ratios with normal pulmonary surfactant. In addition, endotoxin-treated swine developed signs of disseminated intravascular coagulation, with renal cortical infarcts in 44%, and coronary arterial thrombi in 28% including one transmural myocardial infarction. This effect was observed in the absence of prolonged hypotension in swine and should provide a useful model for further study of the relationship of endotoxin to disseminated intravascular coagulation.", "contents": "Hemodynamic and respiratory responses of conscious swine to E. coli endotoxin. The injection of a sublethal bolus of E. coli into conscious swine produces an early increase in PAP and a decrease in LAP. This hemodynamic effect may be secondary to the pulmonary venous constriction seen in other species, or may relate to demonstrated multiple pulmonary microemboli. Hypoxemia developed in only four of 17 animals although all endotoxin-treated swine showed interstitial edema and elevated wet/dry weight ratios with normal pulmonary surfactant. In addition, endotoxin-treated swine developed signs of disseminated intravascular coagulation, with renal cortical infarcts in 44%, and coronary arterial thrombi in 28% including one transmural myocardial infarction. This effect was observed in the absence of prolonged hypotension in swine and should provide a useful model for further study of the relationship of endotoxin to disseminated intravascular coagulation."}
{"id": "PMID:3665", "title": "Isoaccepting species of serine tRNA coded by bacteriophage T5sto.", "content": "By aminoacyl-tRNA-DNA hybridization and chromatographic analysis, evidence was provided that the bacteriophage T5stO codes for two tRNAser species. Trinucleotide- or polynucleotide-stimulated binding experiments assigned the codons UCC or UCU to these two tRNAser species. They also suggested that the synthesis of these two tRNAser species does not modify the reading capacity for codons less used in Escherichia coli F and corresponds to a different situation compared with the T4-coded tRNA's.", "contents": "Isoaccepting species of serine tRNA coded by bacteriophage T5sto. By aminoacyl-tRNA-DNA hybridization and chromatographic analysis, evidence was provided that the bacteriophage T5stO codes for two tRNAser species. Trinucleotide- or polynucleotide-stimulated binding experiments assigned the codons UCC or UCU to these two tRNAser species. They also suggested that the synthesis of these two tRNAser species does not modify the reading capacity for codons less used in Escherichia coli F and corresponds to a different situation compared with the T4-coded tRNA's."}
{"id": "PMID:3666", "title": "Purification and characterization of mouse interferon with novel affinity sorbents.", "content": "Several novel selective sorbents for mouse interferon are described that exploit the hydrophobic property and glycoprotein nature of this molecule. Low-molecular-weight ligands (hydrocarbons) and high-molecular-weight ligands (bovine serum albumin) immobilized on agarose bind selectively mouse L-cell interferon. The high selectivity of binding is due primarily to a hydrophobic effect, although electrostatic forces are also apparently involved. Mouse L-cell interferon binds to immobilized serum albumin and can be completely recovered by raising the ionic strength of the eluant. The specific activity of interferon preparations can be increased 2,000-fold to a value of 3 x 10(8) reference units per mg of protein in a single step with full recovery of the antiviral activity. A selective adsorption, although to a lesser degree, can be also obtained on hydrocarbon-coated agarose (Affi-Gel 202), resulting in 300-fold purification on desorption. The existence of two major components of mouse interferon was revealed upon its chromatography on the following sorbents: (i) bovine serum albumin-agarose, (ii) omega-carboxypentyl-agarose; and (iii) Bandeiraea simplicifolia lectin-agarose. This report thus provides for the first time a means for efficient and clear-cut separation of interferon components, thus enabling their further characterization.", "contents": "Purification and characterization of mouse interferon with novel affinity sorbents. Several novel selective sorbents for mouse interferon are described that exploit the hydrophobic property and glycoprotein nature of this molecule. Low-molecular-weight ligands (hydrocarbons) and high-molecular-weight ligands (bovine serum albumin) immobilized on agarose bind selectively mouse L-cell interferon. The high selectivity of binding is due primarily to a hydrophobic effect, although electrostatic forces are also apparently involved. Mouse L-cell interferon binds to immobilized serum albumin and can be completely recovered by raising the ionic strength of the eluant. The specific activity of interferon preparations can be increased 2,000-fold to a value of 3 x 10(8) reference units per mg of protein in a single step with full recovery of the antiviral activity. A selective adsorption, although to a lesser degree, can be also obtained on hydrocarbon-coated agarose (Affi-Gel 202), resulting in 300-fold purification on desorption. The existence of two major components of mouse interferon was revealed upon its chromatography on the following sorbents: (i) bovine serum albumin-agarose, (ii) omega-carboxypentyl-agarose; and (iii) Bandeiraea simplicifolia lectin-agarose. This report thus provides for the first time a means for efficient and clear-cut separation of interferon components, thus enabling their further characterization."}
{"id": "PMID:3667", "title": "Induction of prophage SPO2 in Bacillus subtilis: isolation of excised prophage DNA as a covently closed circle.", "content": "Bacillus subtilis tryC2, thyA, thyB, lysogenic for the phage DNA polymerase negative mutant SPO2 susL244, was induced under conditions preventing phage and bacterial DNA synthesis. The biological activity of DNA from induced cells and from uninduced controls was assayed by transformation and transfection, respectively. About 50% of the phage DNA biological activity in DNA extracted from induced cells was resistant to exposure to pH 11.8 TO 11.9. This DNA was operationally defined as alkali-resistant phage DNA. Transforming bacterial DNA from uninduced or induced cells and transfecting DNA from uninduced cells were more than 95% inactivated after exposure to high pH. The alkali-resistant phage DNA was characterized by sucrose gradient centrifugation, by centrifugation in cesium chloride-propidium iodide, and by electron microscopy. It was found to consist of a majority of covalently closed circular DNA molecules. Length measurements of a few relaxed circular molecules indicate a molecular weight of these similar to that previously found for mature SPO2DNA. Attempts to isolate similar covalently closed circular phage DNA from induced bacteria lysogenic for SPO2 phage with a functional DNA polymerase gene were unsuccessful. The gene order in mature and prophage SPO2 was determined by rescue of single and double markers from the respective type of DNA. The data obtained show that prophage DNA is (genetically) permuted relative to mature DNA. The phage attachment site is suggested to be located between genes I and J.", "contents": "Induction of prophage SPO2 in Bacillus subtilis: isolation of excised prophage DNA as a covently closed circle. Bacillus subtilis tryC2, thyA, thyB, lysogenic for the phage DNA polymerase negative mutant SPO2 susL244, was induced under conditions preventing phage and bacterial DNA synthesis. The biological activity of DNA from induced cells and from uninduced controls was assayed by transformation and transfection, respectively. About 50% of the phage DNA biological activity in DNA extracted from induced cells was resistant to exposure to pH 11.8 TO 11.9. This DNA was operationally defined as alkali-resistant phage DNA. Transforming bacterial DNA from uninduced or induced cells and transfecting DNA from uninduced cells were more than 95% inactivated after exposure to high pH. The alkali-resistant phage DNA was characterized by sucrose gradient centrifugation, by centrifugation in cesium chloride-propidium iodide, and by electron microscopy. It was found to consist of a majority of covalently closed circular DNA molecules. Length measurements of a few relaxed circular molecules indicate a molecular weight of these similar to that previously found for mature SPO2DNA. Attempts to isolate similar covalently closed circular phage DNA from induced bacteria lysogenic for SPO2 phage with a functional DNA polymerase gene were unsuccessful. The gene order in mature and prophage SPO2 was determined by rescue of single and double markers from the respective type of DNA. The data obtained show that prophage DNA is (genetically) permuted relative to mature DNA. The phage attachment site is suggested to be located between genes I and J."}
{"id": "PMID:3668", "title": "Escherichia coli capsule bacteriophages. VIII. Fragments of bacteriophage 28-1.", "content": "As described previously, a host capsule depolymerase activity is associated with the particles of Escherichia coli capsule bacteriophage 28-1. This is a large virus with a long, contractile tail terminating in a base plate with spikes. In the present work, isolated virions were exposed to a variety of dissociative reagents and conditions. They were then tested for residual infectivity and depolymerase activity, as well as inspected under an electron microscope. Very mild acid treatment (10 to 15 min at pH 4.0 and 37 C) was found to cause a specific detachment of some phage spikes, together with a moderate drop in both infectivity and depolymerase activity. Large batches of viruses were fragmented in this manner, and the detached spikes were isolated. The host capsule depolymerase activity was found to be associated with these organelles. In negatively stained preparations, the spikes exhibited a length of approximately 18 nm and a thickness of about 5 nm. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, they were found to contain polypeptides with molecular weights of 80,000 and 145, 000.", "contents": "Escherichia coli capsule bacteriophages. VIII. Fragments of bacteriophage 28-1. As described previously, a host capsule depolymerase activity is associated with the particles of Escherichia coli capsule bacteriophage 28-1. This is a large virus with a long, contractile tail terminating in a base plate with spikes. In the present work, isolated virions were exposed to a variety of dissociative reagents and conditions. They were then tested for residual infectivity and depolymerase activity, as well as inspected under an electron microscope. Very mild acid treatment (10 to 15 min at pH 4.0 and 37 C) was found to cause a specific detachment of some phage spikes, together with a moderate drop in both infectivity and depolymerase activity. Large batches of viruses were fragmented in this manner, and the detached spikes were isolated. The host capsule depolymerase activity was found to be associated with these organelles. In negatively stained preparations, the spikes exhibited a length of approximately 18 nm and a thickness of about 5 nm. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, they were found to contain polypeptides with molecular weights of 80,000 and 145, 000."}
{"id": "PMID:3674", "title": "Studies on mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (I). Beta-blocking action of mescaline and its derivatives.", "content": "In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 values of propranolol (PR) and certain trimethoxybenzene derivatives were measured, using isolated guinea pig tracheal chains. Each of PR, mescaline (MES) and its derivatives gave almost the same pA2 values for TMQ and ISO. Introduction of an alkyl group into the N atom of MES increased the affinity to the receptor in the order of methyl and isopropyl as well as the structureactivity relationship of catecholamines, while that of hydroxyl group in the beta-position of the side chain decreased pA2 values. The slopes of the regression lines for anti-TMQ action of MES derivatives as well as PR were almost one, but those for their anti-ISO action were less than 0.3. 3,4,5-Trimethoxyaniline and 3,4,5-trimethoxybenzoic acid had little activity as beta-blocking agents. These results suggest the possibility that TMQ and ISO would interact with the same receptor sites. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed.", "contents": "Studies on mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (I). Beta-blocking action of mescaline and its derivatives. In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 values of propranolol (PR) and certain trimethoxybenzene derivatives were measured, using isolated guinea pig tracheal chains. Each of PR, mescaline (MES) and its derivatives gave almost the same pA2 values for TMQ and ISO. Introduction of an alkyl group into the N atom of MES increased the affinity to the receptor in the order of methyl and isopropyl as well as the structureactivity relationship of catecholamines, while that of hydroxyl group in the beta-position of the side chain decreased pA2 values. The slopes of the regression lines for anti-TMQ action of MES derivatives as well as PR were almost one, but those for their anti-ISO action were less than 0.3. 3,4,5-Trimethoxyaniline and 3,4,5-trimethoxybenzoic acid had little activity as beta-blocking agents. These results suggest the possibility that TMQ and ISO would interact with the same receptor sites. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed."}
{"id": "PMID:3675", "title": "Regulation of tyrosine hydroxylase activity by prostaglandin E1 in guinea pig adrenal gland.", "content": "The action of prostaglandin E1 on tyrosine hydroxylase activity in adrenal slices of guinea pig was studied. The activity of tyrosine hydroxylase and was decreased by the incubation of adrenal slices with prostaglandin E1 at concentrations beyond 2 mug per ml for 2 hours. The activity of tyrosine hydroxylase was stimulated by dibutyryl adenosine 3',5'-monophosphate in slices of guinea pig adrenal glands. Incubation of adrenal slices wtth the combination of PGE1 and DBc-AMP lead to a tyrosine hydroxylase activity higher than that with PGE1 alone, but not as great as DBc-AMP alone. It was suggested that PGE1 inhibited the enzyme activity independently of the cyclic AMP level. Other prostaglandins such as PGA1 and PGB1 were deficient to the extent that the tyrosine hydroxylase activity was decreased. PGE1 inhibited the enzyme activity much to the same extent seen with protein synthesis inhibitors such as cycloheximide and actinomycin D. However, PGE1 did not influence the incorporation of L-leucine-14C into acid insoluble protein. The studies reported here showed that PGE1 inhibited the synthesis of tyrosine hydroxylase.", "contents": "Regulation of tyrosine hydroxylase activity by prostaglandin E1 in guinea pig adrenal gland. The action of prostaglandin E1 on tyrosine hydroxylase activity in adrenal slices of guinea pig was studied. The activity of tyrosine hydroxylase and was decreased by the incubation of adrenal slices with prostaglandin E1 at concentrations beyond 2 mug per ml for 2 hours. The activity of tyrosine hydroxylase was stimulated by dibutyryl adenosine 3',5'-monophosphate in slices of guinea pig adrenal glands. Incubation of adrenal slices wtth the combination of PGE1 and DBc-AMP lead to a tyrosine hydroxylase activity higher than that with PGE1 alone, but not as great as DBc-AMP alone. It was suggested that PGE1 inhibited the enzyme activity independently of the cyclic AMP level. Other prostaglandins such as PGA1 and PGB1 were deficient to the extent that the tyrosine hydroxylase activity was decreased. PGE1 inhibited the enzyme activity much to the same extent seen with protein synthesis inhibitors such as cycloheximide and actinomycin D. However, PGE1 did not influence the incorporation of L-leucine-14C into acid insoluble protein. The studies reported here showed that PGE1 inhibited the synthesis of tyrosine hydroxylase."}
{"id": "PMID:3681", "title": "[The role of HCO3- ATPase in H+ /HCO3-Secretion (author's transl)].", "content": "Active buffer transport, e.g. H+ -secretion by stomach and kidney and HCO3--secretion by pancreas and salivary glands, is linked with the presence of a HCO3-stimulated ATP-Phosphohydrolase. In contrast to (Na+ -k+)-ATPase which is considered to be equivalent to the Na+ pump, the HCO3--ATPase requires only one ion for activation and is insensitive to ouabain. The HCO3--ATPase is found in the plasma membrane of the epithelia, but in contrast to the (Na+ -k+)-ATPase it is located in the luminal cell border. The activity of the HCO3--ATPase changes in parallel along with the rate of active buffer transport, a finding which underlines its importance as a transport enzyme. Several disorders of buffer transport are described which are possibly associated with a defect of the HCO3--ATPase system.", "contents": "[The role of HCO3- ATPase in H+ /HCO3-Secretion (author's transl)]. Active buffer transport, e.g. H+ -secretion by stomach and kidney and HCO3--secretion by pancreas and salivary glands, is linked with the presence of a HCO3-stimulated ATP-Phosphohydrolase. In contrast to (Na+ -k+)-ATPase which is considered to be equivalent to the Na+ pump, the HCO3--ATPase requires only one ion for activation and is insensitive to ouabain. The HCO3--ATPase is found in the plasma membrane of the epithelia, but in contrast to the (Na+ -k+)-ATPase it is located in the luminal cell border. The activity of the HCO3--ATPase changes in parallel along with the rate of active buffer transport, a finding which underlines its importance as a transport enzyme. Several disorders of buffer transport are described which are possibly associated with a defect of the HCO3--ATPase system."}
{"id": "PMID:3684", "title": "[Interlocking medullary nailing. Indications, technic with a new guiding instrument. Analysis of the 1st 50 operations].", "content": "After a review of K\u00fcntsher's intramedullary nailing, the author resumed the informations about the interlocking medullary nail and its technique. A new device, as a guide instrument for easier application of the transverse bolts was constructed on the basis of authors concept. Using the new technique and guide instrument X-ray television controll is not necessary for placing the bolts in their right places through a small incision. The time of operation and the risk of infection was also diminished by the new technique. The indications for the interlocking medullary nailing have been completed by the author with the pathologic fractures. The first 50 cases, treated by the new technique of the interlocking medullary nailing are analysed and a few cases are reported in detail. Good results have been obtained as regards both the bone union and the functional results. Based on the good results the new technique of the interlocking medullary nailing is recommended by the author.", "contents": "[Interlocking medullary nailing. Indications, technic with a new guiding instrument. Analysis of the 1st 50 operations]. After a review of K\u00fcntsher's intramedullary nailing, the author resumed the informations about the interlocking medullary nail and its technique. A new device, as a guide instrument for easier application of the transverse bolts was constructed on the basis of authors concept. Using the new technique and guide instrument X-ray television controll is not necessary for placing the bolts in their right places through a small incision. The time of operation and the risk of infection was also diminished by the new technique. The indications for the interlocking medullary nailing have been completed by the author with the pathologic fractures. The first 50 cases, treated by the new technique of the interlocking medullary nailing are analysed and a few cases are reported in detail. Good results have been obtained as regards both the bone union and the functional results. Based on the good results the new technique of the interlocking medullary nailing is recommended by the author."}
{"id": "PMID:3682", "title": "[Tissue specific inhibition of lymphocyte proliferation by spleen extract (lymphocyte chalone) (author's transl)].", "content": "Aqueous spleen extracts were purified using acetone precipitation, membrane filtration, affinity chromatography, and dialysis. These extracts were able to inhibit thymidine incorporation into lymphoid cells (MKT-CH and PHA-stimulated lymphocyte cultures). They did not influence non lymphoid tissue (melanoma cells Mel Ei 78 and Ehrlich ascites cells). The inhibition was reversible and the purified extracts were not cytotoxic. The extracts correspond to a chalone. Their importance for prevention of graft versus host reaction and for treatment of lymphoproliferative diseases is discussed.", "contents": "[Tissue specific inhibition of lymphocyte proliferation by spleen extract (lymphocyte chalone) (author's transl)]. Aqueous spleen extracts were purified using acetone precipitation, membrane filtration, affinity chromatography, and dialysis. These extracts were able to inhibit thymidine incorporation into lymphoid cells (MKT-CH and PHA-stimulated lymphocyte cultures). They did not influence non lymphoid tissue (melanoma cells Mel Ei 78 and Ehrlich ascites cells). The inhibition was reversible and the purified extracts were not cytotoxic. The extracts correspond to a chalone. Their importance for prevention of graft versus host reaction and for treatment of lymphoproliferative diseases is discussed."}
{"id": "PMID:3685", "title": "[Supporting role of the fibula in tibial fractures].", "content": "The possibilities of the supporting effect of the fibula and of its preclusion are discussed. The indication of the fibulotomia is dealt with. According to the authors' standpoint in the case of the anatomical reposition of the tibial fracture and after its staple synthesis the supporting effect of the fibula is not be be feared. In these cases the reposition and the osteosynthesis of the fibula neutralize fairly well also the motive forces acting on the tibial fracture.", "contents": "[Supporting role of the fibula in tibial fractures]. The possibilities of the supporting effect of the fibula and of its preclusion are discussed. The indication of the fibulotomia is dealt with. According to the authors' standpoint in the case of the anatomical reposition of the tibial fracture and after its staple synthesis the supporting effect of the fibula is not be be feared. In these cases the reposition and the osteosynthesis of the fibula neutralize fairly well also the motive forces acting on the tibial fracture."}
{"id": "PMID:3686", "title": "[Clinical aspects and pathology of traumatic lesions of the optic nerve].", "content": "The cause of the unilateral complete blindness (amaurosis traumatica) occurring in the case of closed cranial injury has been sought for in the optic nerve canal (canalis opticus syndrome). For the decompression of the optic nerve surgical approach has been performed in several institutes and by various neurosurgeons. These interventions lead to no result, irrespective of the time of the operation or the surgical technique. On the basis of the data of the literature and their material the authors came to the conclusion that since the alteration of the optic nerve has been histologically observed not only in the area of the optic nerve, but also in the free intracranial and intraorbital sector, this was the cause of the failure. The authors' five cases are demonstrated with light and electron microscopic examinations.", "contents": "[Clinical aspects and pathology of traumatic lesions of the optic nerve]. The cause of the unilateral complete blindness (amaurosis traumatica) occurring in the case of closed cranial injury has been sought for in the optic nerve canal (canalis opticus syndrome). For the decompression of the optic nerve surgical approach has been performed in several institutes and by various neurosurgeons. These interventions lead to no result, irrespective of the time of the operation or the surgical technique. On the basis of the data of the literature and their material the authors came to the conclusion that since the alteration of the optic nerve has been histologically observed not only in the area of the optic nerve, but also in the free intracranial and intraorbital sector, this was the cause of the failure. The authors' five cases are demonstrated with light and electron microscopic examinations."}
{"id": "PMID:3687", "title": "[Preservation of crushed extremities].", "content": "For the conservation of crushed extremities all achievements of up-to-date traumatology are to be used. The impairement of the seriously crushed extremity displays a certain similarity to the polytraumatism involving the whole organism. This is to be taken into consideration in the surgical treatment. Conserving the vitality of the extremity deferred treatment and reconstructive operations at a later date become possible. As absolute rule must be in view that all cases are to be examined with the greatest care and individually, as regards the surgical treatment.", "contents": "[Preservation of crushed extremities]. For the conservation of crushed extremities all achievements of up-to-date traumatology are to be used. The impairement of the seriously crushed extremity displays a certain similarity to the polytraumatism involving the whole organism. This is to be taken into consideration in the surgical treatment. Conserving the vitality of the extremity deferred treatment and reconstructive operations at a later date become possible. As absolute rule must be in view that all cases are to be examined with the greatest care and individually, as regards the surgical treatment."}
{"id": "PMID:3689", "title": "[Experience with the management of subtalar dislocation].", "content": "In 10 and 3 years resp., material of two surgical departments - with great material - 10 cases of luxation - without fracture - occurred in the subtaler joint have been treated. All 10 patients suffered covered, subtaler dislocations. After conservative treatment all 10 patients recovered and are back at work.", "contents": "[Experience with the management of subtalar dislocation]. In 10 and 3 years resp., material of two surgical departments - with great material - 10 cases of luxation - without fracture - occurred in the subtaler joint have been treated. All 10 patients suffered covered, subtaler dislocations. After conservative treatment all 10 patients recovered and are back at work."}
{"id": "PMID:3690", "title": "[Treatment of contracture of the finger joints by capsulectomy and spring-splints].", "content": "The treatment performed in 84 cases of contracted PIP articulations is reported, -in 50 cases the treatment has been carried out with spring-actuated splint and in 34 cases with capsulectomy. It has been found by the authors that the results of the physico-therapeutic treatment used so-far may be still more improved, -satisfactory result has been obtained in more than the half of the author's cases. The advantages of the use of the spring-acutatd splint as against Quengel's method are emphasized. Capsulectomy performed in very serious cases resulted in improvement of the articulation motion in 50% of the cases.", "contents": "[Treatment of contracture of the finger joints by capsulectomy and spring-splints]. The treatment performed in 84 cases of contracted PIP articulations is reported, -in 50 cases the treatment has been carried out with spring-actuated splint and in 34 cases with capsulectomy. It has been found by the authors that the results of the physico-therapeutic treatment used so-far may be still more improved, -satisfactory result has been obtained in more than the half of the author's cases. The advantages of the use of the spring-acutatd splint as against Quengel's method are emphasized. Capsulectomy performed in very serious cases resulted in improvement of the articulation motion in 50% of the cases."}
{"id": "PMID:3691", "title": "[Experimental single-stage reconstruction of the tendon sheath and flexor tendon (free tendon graft, using a vein for sheath on the flexor tendon in dogs)].", "content": "In dog experiments the flexor tendons of the 2nd toe together with their tendon sheaths have been extirpated by the authors. Then on the place of the tendon sheath complex-resembling the human hand's \"no man's land\" -for the substitution of the tendon sheath-free inautotransplants with long vein-segments have been grafted in one sitting. Resuming the results of the macroscopic and light microscopic examinations carried out in definite times it has been found by the authors that while the vein segment was revascularized in the course of one or two weeks, the regeneration of the tendon transplant was slightly retarded. Between the vein and the tendon but adhesion of medium degree were found. The possibilities of the clinical use of the method are discussed.", "contents": "[Experimental single-stage reconstruction of the tendon sheath and flexor tendon (free tendon graft, using a vein for sheath on the flexor tendon in dogs)]. In dog experiments the flexor tendons of the 2nd toe together with their tendon sheaths have been extirpated by the authors. Then on the place of the tendon sheath complex-resembling the human hand's \"no man's land\" -for the substitution of the tendon sheath-free inautotransplants with long vein-segments have been grafted in one sitting. Resuming the results of the macroscopic and light microscopic examinations carried out in definite times it has been found by the authors that while the vein segment was revascularized in the course of one or two weeks, the regeneration of the tendon transplant was slightly retarded. Between the vein and the tendon but adhesion of medium degree were found. The possibilities of the clinical use of the method are discussed."}
{"id": "PMID:3692", "title": "[Reconstruction of the injured flexor tendon in the proximal half of the \"no man's land\" by a modified method (tendon sheath reconstruction using a vein graft)].", "content": "On the basis of long years' experiences the \"no man's land\" has been divided by the author into 2 parts: the proximal and the distal part. For the treatment of the flexor tendon lesions occurred in the distal part of the author advocates his method already published: in the \"tendon sheath\" formed from the vein its \"bridging\" by free tendon transplant. If the lesion occurred in the proximal part, the formation of a long \"tendon sheath\" from a vein and then its \"bridging\" by long tendon transplant are advocated by the author.", "contents": "[Reconstruction of the injured flexor tendon in the proximal half of the \"no man's land\" by a modified method (tendon sheath reconstruction using a vein graft)]. On the basis of long years' experiences the \"no man's land\" has been divided by the author into 2 parts: the proximal and the distal part. For the treatment of the flexor tendon lesions occurred in the distal part of the author advocates his method already published: in the \"tendon sheath\" formed from the vein its \"bridging\" by free tendon transplant. If the lesion occurred in the proximal part, the formation of a long \"tendon sheath\" from a vein and then its \"bridging\" by long tendon transplant are advocated by the author."}
{"id": "PMID:3693", "title": "[Isolated luxation of the trapezium bone].", "content": "The luxation of the os trapezium without fracture - a very rare lesion - is reported. This is the first publication in the Hungarian literature of this sort. Proper diagnosis was established after the patient's admission. Covered reduction of the luxation was made, and the luxated bone was fixed by percutaneous wiring and plaster-bandage. The patient recovered without complications.", "contents": "[Isolated luxation of the trapezium bone]. The luxation of the os trapezium without fracture - a very rare lesion - is reported. This is the first publication in the Hungarian literature of this sort. Proper diagnosis was established after the patient's admission. Covered reduction of the luxation was made, and the luxated bone was fixed by percutaneous wiring and plaster-bandage. The patient recovered without complications."}
{"id": "PMID:3694", "title": "[Amputation and rehabilitation].", "content": "Amputation is maybe the oldest and most frequent surgical intervention. After the review of the concept of rehabilitation, its methods and the improvement of the rehabilitation technique the earling opinions in respect of the height of the amputation, the surgical technique and the post-operative treatment - the use of a prosthesis included - are discussed by the author.", "contents": "[Amputation and rehabilitation]. Amputation is maybe the oldest and most frequent surgical intervention. After the review of the concept of rehabilitation, its methods and the improvement of the rehabilitation technique the earling opinions in respect of the height of the amputation, the surgical technique and the post-operative treatment - the use of a prosthesis included - are discussed by the author."}
{"id": "PMID:3695", "title": "[Special care of injured patients after returning to work].", "content": "The changes in the type of injury, as well as in the treatment, and the consequences observed during the check-up of the injured patients set the problem of the prolonged care of the patients after the articular fractions of the lower extremity, amputation, arthroplasty, and severe lesions of the hand. Systematic observation, eventual change of the life and work conditions, temporary rest, conservative treatment or surgical intervention performed in due time allow the prevention of serious complications and assure lasting recovery.", "contents": "[Special care of injured patients after returning to work]. The changes in the type of injury, as well as in the treatment, and the consequences observed during the check-up of the injured patients set the problem of the prolonged care of the patients after the articular fractions of the lower extremity, amputation, arthroplasty, and severe lesions of the hand. Systematic observation, eventual change of the life and work conditions, temporary rest, conservative treatment or surgical intervention performed in due time allow the prevention of serious complications and assure lasting recovery."}
{"id": "PMID:3697", "title": "Chemical injuries of the upper extremity.", "content": "The prompt recognition and management (Tables 8-1 and 8-2) of chemical burns of the upper extremity may prevent injury to the deep structures of the hand and may make the difference between satisfactory rehabilitation and crippling deformities. Immediate irrigation with water is the single most important treatment that can be carried out, and should be continued for at least an hour and often for several hours, depending on the severity of the injury. Precious time should not be wasted hunting for a specific neutralizing agent. Hydrofluoric acid injuries and phosphorus injuries are the two exceptions to this principle. After copious irrigation and d\u00e9bridement, small superficial burns may be treated without dressings or topical therapy. Large partial-thickness burns are best treated with Sulfamylon burn cream and then with with biologic dressings until healing is achieved. Full-thickness injuries of limited extent should be excised and skin-grafted to regain maximum function, and more extensive burns treated in a nonexicisional regimen.", "contents": "Chemical injuries of the upper extremity. The prompt recognition and management (Tables 8-1 and 8-2) of chemical burns of the upper extremity may prevent injury to the deep structures of the hand and may make the difference between satisfactory rehabilitation and crippling deformities. Immediate irrigation with water is the single most important treatment that can be carried out, and should be continued for at least an hour and often for several hours, depending on the severity of the injury. Precious time should not be wasted hunting for a specific neutralizing agent. Hydrofluoric acid injuries and phosphorus injuries are the two exceptions to this principle. After copious irrigation and d\u00e9bridement, small superficial burns may be treated without dressings or topical therapy. Large partial-thickness burns are best treated with Sulfamylon burn cream and then with with biologic dressings until healing is achieved. Full-thickness injuries of limited extent should be excised and skin-grafted to regain maximum function, and more extensive burns treated in a nonexicisional regimen."}
{"id": "PMID:3698", "title": "Intraspecific variations in the hemolymph of Biomphalaria glabrata, a snail host of Schistosoma mansoni.", "content": "An attempt was made to characterize the hemolymph of Biomphalaria glabrata with reference to \"normal\" intra-specific variation, i.e., both inter- and intra-strain differences. Total protein concentration, per cent hemoglobin, pH, and osmolarity were studied. Seven geographic strains of B, glabrata were examined. In addition, observations were made on the hemolymph of Biomphalaria straminea, several strains of Helisoma caribaeum, and on B. glabrata subjected to infection with Schistosoma mansoni or to periods of starvation. Intra-strain differences in total protein concentration and total hemoglobin concentration in B. glabrata appeared to be more closely related with snail size than with absolute age. Inter-strain variation in B. glabrata was also noted, but the differences were of the same magnitude as those from intra-strain samples. Significant differences in total protein concentration were observed, however, between the means of similar size B. glabrata, B. straminea and H. caribaeum. The osmolatity of the hemolymph from different size B. glabrata was similar as were the osmolalities of the hemolymph from similar size snails of different strains. However, all B. glabrata strains exhibited hemolymph osmolalities lower than observed in strains of H. caribaeum. Infection with S. mansoni reduced the protein concentration of B. glabrata hemolymph. Differences were noted as early as 1.5-24 hr post-infection, with significant alterations occurring at about 11 days post-infection. To a lesser extent, starvation also depleted the protein content of the hemolymph.", "contents": "Intraspecific variations in the hemolymph of Biomphalaria glabrata, a snail host of Schistosoma mansoni. An attempt was made to characterize the hemolymph of Biomphalaria glabrata with reference to \"normal\" intra-specific variation, i.e., both inter- and intra-strain differences. Total protein concentration, per cent hemoglobin, pH, and osmolarity were studied. Seven geographic strains of B, glabrata were examined. In addition, observations were made on the hemolymph of Biomphalaria straminea, several strains of Helisoma caribaeum, and on B. glabrata subjected to infection with Schistosoma mansoni or to periods of starvation. Intra-strain differences in total protein concentration and total hemoglobin concentration in B. glabrata appeared to be more closely related with snail size than with absolute age. Inter-strain variation in B. glabrata was also noted, but the differences were of the same magnitude as those from intra-strain samples. Significant differences in total protein concentration were observed, however, between the means of similar size B. glabrata, B. straminea and H. caribaeum. The osmolatity of the hemolymph from different size B. glabrata was similar as were the osmolalities of the hemolymph from similar size snails of different strains. However, all B. glabrata strains exhibited hemolymph osmolalities lower than observed in strains of H. caribaeum. Infection with S. mansoni reduced the protein concentration of B. glabrata hemolymph. Differences were noted as early as 1.5-24 hr post-infection, with significant alterations occurring at about 11 days post-infection. To a lesser extent, starvation also depleted the protein content of the hemolymph."}
{"id": "PMID:3720", "title": "[Relevance of biochemistry in diagnosis and development of alcoholic liver disease (author's transl)].", "content": "In a group of 205 patients with alcoholic diseases of liver the diagnostic relevance of biochemical tests (GOT, GPT, AP, GGTP, BSP) was reconsidered with discriminatory process (separation of diagnosis). The group contained 16 patients with nutritional-caused and 41 cases with alcoholic-caused fatty-infiltration of liver. 148 patients showed a toxic chronic liver disease; 52 a chronic hepatitis and 96 cirrhosis of liver. Laparoscopy and morphology guaranteed the clinical diagnosis and therefore the accuracy of biochemistry in separation of diagnosis was given. The biochemical tests were not able to offer a separation of fatty-infiltration with reference to cause, changes of the process in toxic hepatitis and cirrhosis were announced. Intersection in several cases was noticed and biochemical tests were not able to substitute endoscopy and morphology for clinical and diagnostic use in all cases. In every regard the enzyme-tests,--above mentioned--, and determination of sulfobromthalein are aptly to development of diseases and deficiency of alcohol.", "contents": "[Relevance of biochemistry in diagnosis and development of alcoholic liver disease (author's transl)]. In a group of 205 patients with alcoholic diseases of liver the diagnostic relevance of biochemical tests (GOT, GPT, AP, GGTP, BSP) was reconsidered with discriminatory process (separation of diagnosis). The group contained 16 patients with nutritional-caused and 41 cases with alcoholic-caused fatty-infiltration of liver. 148 patients showed a toxic chronic liver disease; 52 a chronic hepatitis and 96 cirrhosis of liver. Laparoscopy and morphology guaranteed the clinical diagnosis and therefore the accuracy of biochemistry in separation of diagnosis was given. The biochemical tests were not able to offer a separation of fatty-infiltration with reference to cause, changes of the process in toxic hepatitis and cirrhosis were announced. Intersection in several cases was noticed and biochemical tests were not able to substitute endoscopy and morphology for clinical and diagnostic use in all cases. In every regard the enzyme-tests,--above mentioned--, and determination of sulfobromthalein are aptly to development of diseases and deficiency of alcohol."}
{"id": "PMID:3727", "title": "Proline endopeptidase and exopeptidase activity in polymorphonuclear granulocytes.", "content": "Peptidases capable of releasing proline residues from polypeptides are present in the cytoplasmic fraction of rabbit polymorphonuclear granulocytes. This was shown with peptide substrates where proline is present either at the carboxy-terminal or within the polypeptide chain. Lysosomal and plasma membrane enzymes were inactive towards such polypeptides. The proline residue was hydrolyzed at either its amino end or its carboxy end. It is noteworthy that a Pro:Pro bond was cleaved both in the pentapeptide Thr-Lys-Pro-Arg and the dipeptide Pro:Pro.", "contents": "Proline endopeptidase and exopeptidase activity in polymorphonuclear granulocytes. Peptidases capable of releasing proline residues from polypeptides are present in the cytoplasmic fraction of rabbit polymorphonuclear granulocytes. This was shown with peptide substrates where proline is present either at the carboxy-terminal or within the polypeptide chain. Lysosomal and plasma membrane enzymes were inactive towards such polypeptides. The proline residue was hydrolyzed at either its amino end or its carboxy end. It is noteworthy that a Pro:Pro bond was cleaved both in the pentapeptide Thr-Lys-Pro-Arg and the dipeptide Pro:Pro."}
{"id": "PMID:3728", "title": "[A compact form of DNA in solution. 2. Peculiarities of acidic titration of double-stranded DNA in PEG-containing water-salt solutions].", "content": "The formation of compact double-stranded DNA molecules in PEG-containing watersalt solutions (0.3 M NaCl) may be observed within the pH-range 3-10; i.e. under conditions at which parameters of double-stranded DNA helices are not strongly different from those of B-form. At pH less than 3, when regularity of double helices is significantly changed, the formation of the specific compact particles of DNA in PEG-containing solutions does not take place. Denaturation of the compact form of DNA in PEG-containing solution is accompanied by disappearance of the negative band in CD spectrum. Hyperchromic effect of denaturation of DNA compact form is uninformative because of the influence of the light-scattering by compact DNA molecules.", "contents": "[A compact form of DNA in solution. 2. Peculiarities of acidic titration of double-stranded DNA in PEG-containing water-salt solutions]. The formation of compact double-stranded DNA molecules in PEG-containing watersalt solutions (0.3 M NaCl) may be observed within the pH-range 3-10; i.e. under conditions at which parameters of double-stranded DNA helices are not strongly different from those of B-form. At pH less than 3, when regularity of double helices is significantly changed, the formation of the specific compact particles of DNA in PEG-containing solutions does not take place. Denaturation of the compact form of DNA in PEG-containing solution is accompanied by disappearance of the negative band in CD spectrum. Hyperchromic effect of denaturation of DNA compact form is uninformative because of the influence of the light-scattering by compact DNA molecules."}
{"id": "PMID:3729", "title": "[Changes in the chemical composition and physico-chemical characteristics of chromatin from spleens of mice during immunogenesis].", "content": "Comparative studies have been carried out for the chemical composition and physico-chemical characteristics of chromatin isolated from spleens of non-immunized and immunized mice. It is found that the chromatin from spleens of immunized mice contains significantly more non-histone proteins and RNA, while the quantity of histone proteins is unaltered. The melting temperatures of chromatin from spleens of non-immunized and immunized mice in 2.5-10(-4) M EDTA (pH 8.0) are 76.8+/-1.50 degrees and 74.4+/-1.10 degrees, respectively. DNA isolated from chromatin melts at 40 degrees. The melting of chromatin was followed in 5 mM sodium-cacodylate buffer (pH 7.0)+1.5-10(-4) M EDTA containing increasing concentrations of urea. The results show that during immunogenesis the changes of the chemical composition of the chromatin are accompanied by certain destabilisation of DNP complex.", "contents": "[Changes in the chemical composition and physico-chemical characteristics of chromatin from spleens of mice during immunogenesis]. Comparative studies have been carried out for the chemical composition and physico-chemical characteristics of chromatin isolated from spleens of non-immunized and immunized mice. It is found that the chromatin from spleens of immunized mice contains significantly more non-histone proteins and RNA, while the quantity of histone proteins is unaltered. The melting temperatures of chromatin from spleens of non-immunized and immunized mice in 2.5-10(-4) M EDTA (pH 8.0) are 76.8+/-1.50 degrees and 74.4+/-1.10 degrees, respectively. DNA isolated from chromatin melts at 40 degrees. The melting of chromatin was followed in 5 mM sodium-cacodylate buffer (pH 7.0)+1.5-10(-4) M EDTA containing increasing concentrations of urea. The results show that during immunogenesis the changes of the chemical composition of the chromatin are accompanied by certain destabilisation of DNP complex."}
{"id": "PMID:3737", "title": "Correction of severe combined immunodeficiency by fetal liver cells.", "content": "As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin A by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. Chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency.", "contents": "Correction of severe combined immunodeficiency by fetal liver cells. As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin A by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. Chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency."}
{"id": "PMID:3730", "title": "[Kinetics and mechanism of the 3H to 1H in C(8)H groups of purine derivatives].", "content": "The pH-dependence of the 3H to 1H exchange between water and C(8)H groups of purine, adenine, 9-methyladenine, 7-methyladenine, hypoxanthine, guanine, xanthine as well as C(2)H groups of imidazole and benzimidazole was studied. It was shown  that within the pH-ranges, where the majority of molecules under study are non-ionized, the values of observed rate constant (kobs) do not depend on pH. Beyond these ranges the values of k(obs) are increased or decreased depending on the type of ionizaiton of the compound under study in appropriate pH range. The observed pH dependence of the 3H to 1H exchange is in a good quantitative agreement with ylide mechanism of the exchange reaction. According to this mechanism the 3H--1H exchange takes place in N(7)-protonated forms of the purine derivatives and in zwitterions with positive charge on N(7). The ylide mechanism of the exchange reaction is also suggested by the fact that the true exchange rate constants (k+) of protonated forms of the studied compounds, calculated from the values of k(ods), rises linearly with the increase of their protonation constant (Ka1)--the tenfold increase of Ka1 leads to about four-fold rise of k+. The knowledge of 1h to 3H exchange mechanism in C(8)H groups of purine derivatives allows to estimate alterations of reactivity of the purine residues in polynucleotides and nucleic acids depending on their conformation.", "contents": "[Kinetics and mechanism of the 3H to 1H in C(8)H groups of purine derivatives]. The pH-dependence of the 3H to 1H exchange between water and C(8)H groups of purine, adenine, 9-methyladenine, 7-methyladenine, hypoxanthine, guanine, xanthine as well as C(2)H groups of imidazole and benzimidazole was studied. It was shown  that within the pH-ranges, where the majority of molecules under study are non-ionized, the values of observed rate constant (kobs) do not depend on pH. Beyond these ranges the values of k(obs) are increased or decreased depending on the type of ionizaiton of the compound under study in appropriate pH range. The observed pH dependence of the 3H to 1H exchange is in a good quantitative agreement with ylide mechanism of the exchange reaction. According to this mechanism the 3H--1H exchange takes place in N(7)-protonated forms of the purine derivatives and in zwitterions with positive charge on N(7). The ylide mechanism of the exchange reaction is also suggested by the fact that the true exchange rate constants (k+) of protonated forms of the studied compounds, calculated from the values of k(ods), rises linearly with the increase of their protonation constant (Ka1)--the tenfold increase of Ka1 leads to about four-fold rise of k+. The knowledge of 1h to 3H exchange mechanism in C(8)H groups of purine derivatives allows to estimate alterations of reactivity of the purine residues in polynucleotides and nucleic acids depending on their conformation."}
{"id": "PMID:3753", "title": "Cyclic AMP and neuroendocrine influence upon forelimb regeneration in the adult newt, Notophthalmus viridescens.", "content": "The influence of the nervous and endocrine systems upon successive stages of limb regeneration suggest possible neuroendocrine interaction(s). Intraperitoneal injections of various agents had no effects upon blastema formation. Chlorpromazine, administered alone or with hormones, retarded morphogenesis. Prolactin, dibutyryl cAMP (db-cAMP), theophylline, and acetylcholine accelerated morphogenesis. 5'-AMP had no effect. Only db-cAMP countered the chlorpromazine-induced retardation of morphogenesis. These results suggest that neuroendocrine influences, possibly cAMP-mediated, direct, in part, the morphogenesis of the regeneration blastema.", "contents": "Cyclic AMP and neuroendocrine influence upon forelimb regeneration in the adult newt, Notophthalmus viridescens. The influence of the nervous and endocrine systems upon successive stages of limb regeneration suggest possible neuroendocrine interaction(s). Intraperitoneal injections of various agents had no effects upon blastema formation. Chlorpromazine, administered alone or with hormones, retarded morphogenesis. Prolactin, dibutyryl cAMP (db-cAMP), theophylline, and acetylcholine accelerated morphogenesis. 5'-AMP had no effect. Only db-cAMP countered the chlorpromazine-induced retardation of morphogenesis. These results suggest that neuroendocrine influences, possibly cAMP-mediated, direct, in part, the morphogenesis of the regeneration blastema."}
{"id": "PMID:3759", "title": "Impaired urinary acidification in the hypothyroid rat.", "content": "Since abnormalities in the renal handling of sodium and water in both the proximal and distal tubule have been described in primary hypothyroidism, this study was undertaken to examine renal tubular hydrogen secretion in this disorder. Metabolic acidosis was induced in hypothyroid rats (H) and their age matched controls (C) by the administration of an oral ammonium chloride load of 0.15 g/24 h/kg for three days. On day 3 animals were prepared for clearance and acid-base studies, receiving an infusion of Ringer's solution of 0.6 ml/hr/100 g during surgery and the experimental procedure. A 26% decrease in GFR (P less than 0.005) and a doubling in fractional excretion of sodium (P less than 0.02) were observed in H rats. The lowest blood pH and average bicarbonate concentration and the excretion of chloride were similar in the two groups, indicating that the acid load was reabsorbed and led to similar degrees of systemic acidification. Urine flow also was comparable in the two groups. Minimal urine pH after NH4Cl was 6.21 +/- 0.06 in H and 5.68 +/- 0.09 in C (P less than 0.001). Ammonium excretion was 28% (P less than 0.05) lower in H than in C. The defect in urine acidification in H was only partially corrected after 5 days on a low sodium diet and DOCA administration for 2 days. Fractional bicarbonate excretion at normal blood pH and bicarbonate concentration was not different in the two groups. These data indicate that hypothyroid rats have a mild defect in urine acidification and that it is localized predominantly in the distal tubule.", "contents": "Impaired urinary acidification in the hypothyroid rat. Since abnormalities in the renal handling of sodium and water in both the proximal and distal tubule have been described in primary hypothyroidism, this study was undertaken to examine renal tubular hydrogen secretion in this disorder. Metabolic acidosis was induced in hypothyroid rats (H) and their age matched controls (C) by the administration of an oral ammonium chloride load of 0.15 g/24 h/kg for three days. On day 3 animals were prepared for clearance and acid-base studies, receiving an infusion of Ringer's solution of 0.6 ml/hr/100 g during surgery and the experimental procedure. A 26% decrease in GFR (P less than 0.005) and a doubling in fractional excretion of sodium (P less than 0.02) were observed in H rats. The lowest blood pH and average bicarbonate concentration and the excretion of chloride were similar in the two groups, indicating that the acid load was reabsorbed and led to similar degrees of systemic acidification. Urine flow also was comparable in the two groups. Minimal urine pH after NH4Cl was 6.21 +/- 0.06 in H and 5.68 +/- 0.09 in C (P less than 0.001). Ammonium excretion was 28% (P less than 0.05) lower in H than in C. The defect in urine acidification in H was only partially corrected after 5 days on a low sodium diet and DOCA administration for 2 days. Fractional bicarbonate excretion at normal blood pH and bicarbonate concentration was not different in the two groups. These data indicate that hypothyroid rats have a mild defect in urine acidification and that it is localized predominantly in the distal tubule."}
{"id": "PMID:3757", "title": "[2 new species of microsporidians (Protozoa, Microsporidia) from mosquitoes of the family Chironomidae].", "content": "Two new species of microsporidians are described from the mosquitoes of the genus Chironomus collected in water bodies of the north-eastern USSR. Bacillidium chironomi sp. n. injuring the adipose tissue of the fourth stage larvae of Chironomus dorsalis Mg. has rod-shaped spores 15 (11 to 19) x 0.7 (0.6 to 0.9) mu in size. Duboscqia chironomi sp. n. injures the adipose tissue of the fourth stage larvae of Chironomus plumosus L. Fresh spores of this species are egg-shaped, 6.2 (5.8 to 6.5) x 3.8 (3.6 to 4.0) mu in size. When stained according to the Romanovsky-Gimza method the spores are 5.4 (4.9 to 5.8) x 3.8 (3.6 to 4.1) mu in size. Some peculiarities of the nuclei fission in the sporants of Duboscqia chironomi sp. n., are discussed.", "contents": "[2 new species of microsporidians (Protozoa, Microsporidia) from mosquitoes of the family Chironomidae]. Two new species of microsporidians are described from the mosquitoes of the genus Chironomus collected in water bodies of the north-eastern USSR. Bacillidium chironomi sp. n. injuring the adipose tissue of the fourth stage larvae of Chironomus dorsalis Mg. has rod-shaped spores 15 (11 to 19) x 0.7 (0.6 to 0.9) mu in size. Duboscqia chironomi sp. n. injures the adipose tissue of the fourth stage larvae of Chironomus plumosus L. Fresh spores of this species are egg-shaped, 6.2 (5.8 to 6.5) x 3.8 (3.6 to 4.0) mu in size. When stained according to the Romanovsky-Gimza method the spores are 5.4 (4.9 to 5.8) x 3.8 (3.6 to 4.1) mu in size. Some peculiarities of the nuclei fission in the sporants of Duboscqia chironomi sp. n., are discussed."}
{"id": "PMID:3760", "title": "Electrical responses of isolated Nitella protoplasm--excitations or artifacts?", "content": "Isolated protoplasmic droplets of the alga Nitella were investigated with microelectrodes under current clamp conditions. The following observations were made: 1. Long pulses of either polarity yielded almost symmetric current-voltage relations. Near the rather small resting potential (inside negative) the measuring points lay on a straight line corresponding to an apparent surface membrane resistance of 1.7 +/- 0.45 komega (mean +/- S.E.M., n=5). 2. Experiments with various pulse programs revealed no mechanism comparable to Na inactivation but stressed the electrical symmetry of the droplet with respect to the resting potential. 3. Changes of the [Ca2+] in the bathing medium between 0 to 10 mM as well as of the pH between 5 and 9 did not influence the responses. Replacing K+ by Na+ (or vice versa) or exchanging NO3 for acetylglycine or Cl- was also ineffective. These observations are not consistent with a normal excitable surface membrane. Similar responses are obtained with a RC network which is described and which may have its substrate in histological peculiarities of the protoplasmic droplet.", "contents": "Electrical responses of isolated Nitella protoplasm--excitations or artifacts? Isolated protoplasmic droplets of the alga Nitella were investigated with microelectrodes under current clamp conditions. The following observations were made: 1. Long pulses of either polarity yielded almost symmetric current-voltage relations. Near the rather small resting potential (inside negative) the measuring points lay on a straight line corresponding to an apparent surface membrane resistance of 1.7 +/- 0.45 komega (mean +/- S.E.M., n=5). 2. Experiments with various pulse programs revealed no mechanism comparable to Na inactivation but stressed the electrical symmetry of the droplet with respect to the resting potential. 3. Changes of the [Ca2+] in the bathing medium between 0 to 10 mM as well as of the pH between 5 and 9 did not influence the responses. Replacing K+ by Na+ (or vice versa) or exchanging NO3 for acetylglycine or Cl- was also ineffective. These observations are not consistent with a normal excitable surface membrane. Similar responses are obtained with a RC network which is described and which may have its substrate in histological peculiarities of the protoplasmic droplet."}
{"id": "PMID:3761", "title": "The action of Ca2+ , Mg2+ and H+ on the contraction threshold of frog skeletal muscle: Evidence for surface charges controlling electro-mechanical coupling.", "content": "The dependence of the threshold potential for contraction of pH and the concentration of Ca2+ and Mg2+ in the bathing solution was measured in frog skeletal muscle. Decreasing the pH from 10.3 to 4.65 resulted in a threshold shift to more positive potentials. Between pH 6.5 and 8.5 the concentration threshold was almost pH -independent. Increasing [Ca2+]o (in the concentration range 0.5-50 mM) shifted the curves relating contraction threshold to pH to less negative potentials and diminished the overall pH-dependence. The contraction threshold exhibited a similar dependence on [Ca2+]o and [Mg2+]o, the two curves running parallel in the concentration range of 5-50 mM, but Mg2+ was only c. 0.6 as effective as Ca2+. To explain these results a surface charge model is proposed which assumes that two acidic groups, sigma1 and sigma2, and one basic group, sigma3, reside at the outer surface of the membrane of the T-system. Alterations in the extracellular medium exert their influence on the electro-mechanical coupling process by changing the surface potential. The groups will be titrated by protons and their charges screened off by the divalent cations. In addition, Ca2+ was supposed to bind with a weak dissociation constant (23 M) to the two acidic groups. The chosen charge densities are: sigma1 = -0.0085/A2 [= -1e/(10.8 A)2], sigma2 = -0.0037/A2 [= -1e/(16.4 A)2], sigma3 = 0.0028/A2 [= + 1e/(18.9 A)2] with intrinsic dissociation constants KH1 = 10(-2.0)M, KH2 = 10(-4.1)M, and KH3 = 10(-8.5) M. The measured threshold values are satisfactorily described by this model except at extreme alkaline and acid pH values.", "contents": "The action of Ca2+ , Mg2+ and H+ on the contraction threshold of frog skeletal muscle: Evidence for surface charges controlling electro-mechanical coupling. The dependence of the threshold potential for contraction of pH and the concentration of Ca2+ and Mg2+ in the bathing solution was measured in frog skeletal muscle. Decreasing the pH from 10.3 to 4.65 resulted in a threshold shift to more positive potentials. Between pH 6.5 and 8.5 the concentration threshold was almost pH -independent. Increasing [Ca2+]o (in the concentration range 0.5-50 mM) shifted the curves relating contraction threshold to pH to less negative potentials and diminished the overall pH-dependence. The contraction threshold exhibited a similar dependence on [Ca2+]o and [Mg2+]o, the two curves running parallel in the concentration range of 5-50 mM, but Mg2+ was only c. 0.6 as effective as Ca2+. To explain these results a surface charge model is proposed which assumes that two acidic groups, sigma1 and sigma2, and one basic group, sigma3, reside at the outer surface of the membrane of the T-system. Alterations in the extracellular medium exert their influence on the electro-mechanical coupling process by changing the surface potential. The groups will be titrated by protons and their charges screened off by the divalent cations. In addition, Ca2+ was supposed to bind with a weak dissociation constant (23 M) to the two acidic groups. The chosen charge densities are: sigma1 = -0.0085/A2 [= -1e/(10.8 A)2], sigma2 = -0.0037/A2 [= -1e/(16.4 A)2], sigma3 = 0.0028/A2 [= + 1e/(18.9 A)2] with intrinsic dissociation constants KH1 = 10(-2.0)M, KH2 = 10(-4.1)M, and KH3 = 10(-8.5) M. The measured threshold values are satisfactorily described by this model except at extreme alkaline and acid pH values."}
{"id": "PMID:3766", "title": "[Comparison of the pA2 of various beta blocking agents].", "content": "The drug industry is now putting out specific beta 1 or beta 2 beta-blocking agents. The pA2 of various beta-blocking agents were determined on isolated organs-guinea pig atrium and trachea: practolol and acebutolol were considered as specific beta-1 inhibitors; butoxamine was a specific beta-2 inhibitor, while pindolol, oxprenolol, propranolol and alprenolol were specificity free. The pA2 quantifies the action exerted by an inhibitor. Cardioselectivity is expressed by the pA2 left atrium/pA2 trachea ratio. It exceeds 1 000 for practolol, it equals 30 for acebutolol, and is very slight for butoxamine. The pA2 therefore gives a good idea of the potential of the various drugs on the animal's isolated organ. However, these data cannot safely be extrapolated to man. Hence the necessity of conducting clinical pharmacological studies.", "contents": "[Comparison of the pA2 of various beta blocking agents]. The drug industry is now putting out specific beta 1 or beta 2 beta-blocking agents. The pA2 of various beta-blocking agents were determined on isolated organs-guinea pig atrium and trachea: practolol and acebutolol were considered as specific beta-1 inhibitors; butoxamine was a specific beta-2 inhibitor, while pindolol, oxprenolol, propranolol and alprenolol were specificity free. The pA2 quantifies the action exerted by an inhibitor. Cardioselectivity is expressed by the pA2 left atrium/pA2 trachea ratio. It exceeds 1 000 for practolol, it equals 30 for acebutolol, and is very slight for butoxamine. The pA2 therefore gives a good idea of the potential of the various drugs on the animal's isolated organ. However, these data cannot safely be extrapolated to man. Hence the necessity of conducting clinical pharmacological studies."}
{"id": "PMID:3767", "title": "[Effects of adrenergic blockade on adipose tissue lipolysis provoked in cats and humans by intravenous perfusion of isoprenaline].", "content": "An intravenous infusion of isoprenaline (1 mug/kg/mn during 4 h) elicited a rise in serum free fatty acids (FFA) and glucose in anaesthetised cats. The effect reached a peak in 1 h and was then maintained at a plateau level for the remainder of the infusion. Acebutolol and practolol (0,1-10 mg/kg, p.o.) were more potent in reducing the concentration of free fatty acids (FFA) than in lowering glucose. Propranolol was roughly equipotent on FFA and glucose. In 6 fasted human volunteers, an intravenous infusion of isoprenaline (0,03 mug/kg/mn during 15 min) stimulated a rise in serum FFA. Peak values were attained rapidly and FFA levels began to fall soon after the end of the infusion. Blood glucose concentration was not changed. A placebo, given after the first infusion of isoprenaline, did not significantly affect the response to 2 further infusions at 2 and 4 h later. An oral dose of acebutolol (300 mg) largely suppressed the lipolytic effect of the 2nd and 3rd isoprenaline infusions, the degrees of inhibition being 70 p.cent and 85 p.cent respectively. The same dose of practolol was considerably less effective in inhibiting lipolysis (37 p.cent and 25 p.cent inhibition).", "contents": "[Effects of adrenergic blockade on adipose tissue lipolysis provoked in cats and humans by intravenous perfusion of isoprenaline]. An intravenous infusion of isoprenaline (1 mug/kg/mn during 4 h) elicited a rise in serum free fatty acids (FFA) and glucose in anaesthetised cats. The effect reached a peak in 1 h and was then maintained at a plateau level for the remainder of the infusion. Acebutolol and practolol (0,1-10 mg/kg, p.o.) were more potent in reducing the concentration of free fatty acids (FFA) than in lowering glucose. Propranolol was roughly equipotent on FFA and glucose. In 6 fasted human volunteers, an intravenous infusion of isoprenaline (0,03 mug/kg/mn during 15 min) stimulated a rise in serum FFA. Peak values were attained rapidly and FFA levels began to fall soon after the end of the infusion. Blood glucose concentration was not changed. A placebo, given after the first infusion of isoprenaline, did not significantly affect the response to 2 further infusions at 2 and 4 h later. An oral dose of acebutolol (300 mg) largely suppressed the lipolytic effect of the 2nd and 3rd isoprenaline infusions, the degrees of inhibition being 70 p.cent and 85 p.cent respectively. The same dose of practolol was considerably less effective in inhibiting lipolysis (37 p.cent and 25 p.cent inhibition)."}
{"id": "PMID:3769", "title": "Bone marrow transplantation in children.", "content": "Bone marrow transplantation is a new concept in the treatment of leukemia and aplastic anemia. The problems seen in the transplanted patient are abundant and often life-threatening. Caring for these patients offers one of the most exciting challenges of nursing. The nurse not only acquires skill in caring for a patient with leukemia and aplastic anemia, but also becomes knowledgeable in infectious diseases, immunology, fluid and electrolyte balance, and cardiac, respiratory, and renal diseases. The complexity of these patients allows the nurse more direct, comsistent contact with them. As she becomes involved, she is given excellent opportunities for supporting the patient and family through this stressful time. Althoug bone marrow transplantation is an experimental procedure with problems still to be solved, results indicate its value in the treatment of refractory leukemia and aplastic anemia.", "contents": "Bone marrow transplantation in children. Bone marrow transplantation is a new concept in the treatment of leukemia and aplastic anemia. The problems seen in the transplanted patient are abundant and often life-threatening. Caring for these patients offers one of the most exciting challenges of nursing. The nurse not only acquires skill in caring for a patient with leukemia and aplastic anemia, but also becomes knowledgeable in infectious diseases, immunology, fluid and electrolyte balance, and cardiac, respiratory, and renal diseases. The complexity of these patients allows the nurse more direct, comsistent contact with them. As she becomes involved, she is given excellent opportunities for supporting the patient and family through this stressful time. Althoug bone marrow transplantation is an experimental procedure with problems still to be solved, results indicate its value in the treatment of refractory leukemia and aplastic anemia."}
{"id": "PMID:3780", "title": "Control of adenylate cyclase from secretory vesicle membranes by beta-adrenergic agents and nerve growth factor.", "content": "Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of purified secretory vesicle membranes from the adrenal medulla is inhibited by I-isoproterenol and I-epinephrine, as well as by nerve growth factor (NGF). The effect of these agents was found to be dose-dependent and, in the case of the catecholamines, saturable. NGF was active at concentrations as low as 10(-8) M. Oxidized NGF was only minimally active, and insulin was completely inactive. Neither dopamine nor phenylephrine had activity. Inhibition of cyclase by either isoproterenol or epinephrine was blocked by I-propranolol, a specific beta-antagonist, but propranolol by itself had no effect on adenylate cyclase activity. The data indicate that the secretory vesicle membrane has beta-adrenergic receptors coupled to the adenylate cyclase. Propranolol was also found to block the NGF-induced inhibition of cyclase. We conclude that the granule membrane has beta-adrenergic receptors as well as NGF-reactive sites, and that the two may be functionally linked.", "contents": "Control of adenylate cyclase from secretory vesicle membranes by beta-adrenergic agents and nerve growth factor. Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of purified secretory vesicle membranes from the adrenal medulla is inhibited by I-isoproterenol and I-epinephrine, as well as by nerve growth factor (NGF). The effect of these agents was found to be dose-dependent and, in the case of the catecholamines, saturable. NGF was active at concentrations as low as 10(-8) M. Oxidized NGF was only minimally active, and insulin was completely inactive. Neither dopamine nor phenylephrine had activity. Inhibition of cyclase by either isoproterenol or epinephrine was blocked by I-propranolol, a specific beta-antagonist, but propranolol by itself had no effect on adenylate cyclase activity. The data indicate that the secretory vesicle membrane has beta-adrenergic receptors coupled to the adenylate cyclase. Propranolol was also found to block the NGF-induced inhibition of cyclase. We conclude that the granule membrane has beta-adrenergic receptors as well as NGF-reactive sites, and that the two may be functionally linked."}
{"id": "PMID:3781", "title": "Preliminary characterization of the acrasin of the cellular slime mold Polysphondylium violaceum.", "content": "Some species of cellular slime mold do not respond to cyclic AMP as an acrasin, or chemoattractant. In one such species, Polysphondylium violaceum, we have isolated and purified its acrasin and determined some of its chemical properties, which lead us to believe it is a small molecule of less than 1500 daltons. One possibility is that it might be a peptide. The acrasin specifically attracts the amoebae of P. violaceum and P. pallidum and fails to do so for six species of Dictyostelium tested. We also have evidence for a specific acrasinase that inactivates the Polysphondylium acrasin.", "contents": "Preliminary characterization of the acrasin of the cellular slime mold Polysphondylium violaceum. Some species of cellular slime mold do not respond to cyclic AMP as an acrasin, or chemoattractant. In one such species, Polysphondylium violaceum, we have isolated and purified its acrasin and determined some of its chemical properties, which lead us to believe it is a small molecule of less than 1500 daltons. One possibility is that it might be a peptide. The acrasin specifically attracts the amoebae of P. violaceum and P. pallidum and fails to do so for six species of Dictyostelium tested. We also have evidence for a specific acrasinase that inactivates the Polysphondylium acrasin."}
{"id": "PMID:3778", "title": "[The effect of hydrocortisone and insulin on the activity and isoenzymes of typrosine-alpha-ketoglutarate transaminase in the ctyostructures of the livers of rats of different ages].", "content": "Administration of hydrocortisone or insulin and also a simultaneous use of these hormones in a high dose caused a marked elevation of the total activity of tyrosine-alpha-ketoglutaric transaminase and its anode and cathode isoenzymes in the soluble fraction of the liver in the sexually immature (weighing 100-110 g) and mature (weighing 180-200 g) male rats. The stimulating effect of insulin was sharper in the young in comparison with adult animals. Administration of hydrocortisone caused a more pronounced elevation of the total tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria of young rats than in adult animals. Insulin administration increased the activity of tyrosine-alpha-ketoglutaric transaminase in the mitochondria of the liver of the sexually mature male rats without significant changes of this enzyme in the sexually imature rats. A simultaneous injection of hydrocortisone and insulin to the sexaully mature male rats caused the same increase in the tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria as after the administration of glucocorticosteriod alone. As to the sexaully immature males, the activity of the enzyme fell to the normal level. It is supposed that androgens played a significant role in the realization of the inducing action of glucocorticoids and insulin influencing the synthesis of tyrosine-alpha-ketoglutaric transaminase in different directions in the mitochondria of the liver of young and sexually mature animals.", "contents": "[The effect of hydrocortisone and insulin on the activity and isoenzymes of typrosine-alpha-ketoglutarate transaminase in the ctyostructures of the livers of rats of different ages]. Administration of hydrocortisone or insulin and also a simultaneous use of these hormones in a high dose caused a marked elevation of the total activity of tyrosine-alpha-ketoglutaric transaminase and its anode and cathode isoenzymes in the soluble fraction of the liver in the sexually immature (weighing 100-110 g) and mature (weighing 180-200 g) male rats. The stimulating effect of insulin was sharper in the young in comparison with adult animals. Administration of hydrocortisone caused a more pronounced elevation of the total tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria of young rats than in adult animals. Insulin administration increased the activity of tyrosine-alpha-ketoglutaric transaminase in the mitochondria of the liver of the sexually mature male rats without significant changes of this enzyme in the sexually imature rats. A simultaneous injection of hydrocortisone and insulin to the sexaully mature male rats caused the same increase in the tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria as after the administration of glucocorticosteriod alone. As to the sexaully immature males, the activity of the enzyme fell to the normal level. It is supposed that androgens played a significant role in the realization of the inducing action of glucocorticoids and insulin influencing the synthesis of tyrosine-alpha-ketoglutaric transaminase in different directions in the mitochondria of the liver of young and sexually mature animals."}
{"id": "PMID:3797", "title": "Effects of dietary vitamin D and calcium on lysyl oxidase activity in chick bone metaphyses.", "content": "Activity of lysyl oxidase, an enzyme responsible for production of aldehydic precursors for lysine-derived collagen crosslinks, was measured in tibial metaphyses from chicks receiving different dietary levels of vitamin D and Ca for 2 weeks after hatching. Enzyme activities were increased twofold in D-deficient chicks compared to activities from chicks receiving control levels of vitamin D. Addition of Ca to the D-deficient diet had no effect on lysyl oxidase activity. It is suggested that vitamin D may play a role in the age-related decrease in lysyl oxidase activity that normally occurs in chick bone.", "contents": "Effects of dietary vitamin D and calcium on lysyl oxidase activity in chick bone metaphyses. Activity of lysyl oxidase, an enzyme responsible for production of aldehydic precursors for lysine-derived collagen crosslinks, was measured in tibial metaphyses from chicks receiving different dietary levels of vitamin D and Ca for 2 weeks after hatching. Enzyme activities were increased twofold in D-deficient chicks compared to activities from chicks receiving control levels of vitamin D. Addition of Ca to the D-deficient diet had no effect on lysyl oxidase activity. It is suggested that vitamin D may play a role in the age-related decrease in lysyl oxidase activity that normally occurs in chick bone."}
{"id": "PMID:3798", "title": "Factors influencing nonspecific binding of glucocorticoids in myocardial tissue.", "content": "Myocardial slices from the left ventricle of cat hearts were incubated in Krebs-Henseleit buffer containing 10 mM glucose which were gassed with 95% O2 and 5% CO2. Tritiated dexamethasone (DEXA 0.171 MM) or methylprednisolone (MP 0.805 mM) was added under varying conditions of temperature, pH, and in the presence of various metabolic inhibitors. Glucocorticoid uptake by myocardial tissue was found to be temperature-dependent, plateauting after 60 min of incubation at 0.21 mumole of DEXA/g of tissue and 0.95 mumole of MP/g of tissue at 37 degrees. Steroid uptake was retarded about 50% at 0 degrees. Increasing the concentration of either steroid resulted in a linear increase in the uptake of that steroid. Incubation in the presence of metabolic or SH-inhibitors produced no significant changes in glucocorticoid uptake. Optimal glucocorticoid uptake occurred between pH 7.3-7.4. Thus, myocardial cells appear to be able to take up large quantities of glucocorticoids, but the uptake process does not appear to be energy-dependent.", "contents": "Factors influencing nonspecific binding of glucocorticoids in myocardial tissue. Myocardial slices from the left ventricle of cat hearts were incubated in Krebs-Henseleit buffer containing 10 mM glucose which were gassed with 95% O2 and 5% CO2. Tritiated dexamethasone (DEXA 0.171 MM) or methylprednisolone (MP 0.805 mM) was added under varying conditions of temperature, pH, and in the presence of various metabolic inhibitors. Glucocorticoid uptake by myocardial tissue was found to be temperature-dependent, plateauting after 60 min of incubation at 0.21 mumole of DEXA/g of tissue and 0.95 mumole of MP/g of tissue at 37 degrees. Steroid uptake was retarded about 50% at 0 degrees. Increasing the concentration of either steroid resulted in a linear increase in the uptake of that steroid. Incubation in the presence of metabolic or SH-inhibitors produced no significant changes in glucocorticoid uptake. Optimal glucocorticoid uptake occurred between pH 7.3-7.4. Thus, myocardial cells appear to be able to take up large quantities of glucocorticoids, but the uptake process does not appear to be energy-dependent."}
{"id": "PMID:3799", "title": "Arylamidase and cathepsin-A activity of normal and dystrophic human muscle.", "content": "Human skeletal muscle homogenate has been shown to contain enzymes that catalyze the hydrolysis of L-leucyl p-nitroanilide and carbobenzoxyglutamyl-L-tyrosine, known substrates, respectively, for arylamidase and cathepsin A. The muscle arylamidase was found to be inhibited by p-chloromercuribenzoate. Addition of Co2+ resulted in slight stimulation of its activity. Neither ethylenediamine tetraacetate nor thiol compounds had any appreciable effect on the enzyme. When compared to controls, no significant differences in muscle arylamidase levels were observed in patients with muscular dystrophies and certain selected neuromuscular diseases. Cathepsin A was, however, increased in muscles moderately affected by muscular dystrophy and denervating diseases.", "contents": "Arylamidase and cathepsin-A activity of normal and dystrophic human muscle. Human skeletal muscle homogenate has been shown to contain enzymes that catalyze the hydrolysis of L-leucyl p-nitroanilide and carbobenzoxyglutamyl-L-tyrosine, known substrates, respectively, for arylamidase and cathepsin A. The muscle arylamidase was found to be inhibited by p-chloromercuribenzoate. Addition of Co2+ resulted in slight stimulation of its activity. Neither ethylenediamine tetraacetate nor thiol compounds had any appreciable effect on the enzyme. When compared to controls, no significant differences in muscle arylamidase levels were observed in patients with muscular dystrophies and certain selected neuromuscular diseases. Cathepsin A was, however, increased in muscles moderately affected by muscular dystrophy and denervating diseases."}
{"id": "PMID:3808", "title": "Synthesis of some new phenothiazine derivatives of expected medicinal value.", "content": "2-Chloroacetyl phenothiazines were reacted with certain phenols and salts of some acids under different conditions to yield 2-substituted acetylphenothiazines. Another series of 10-substituted phenothiazines was synthesized by treatment of 10-chloroacetylphenothiazine with either the appropriate amines or salts of the respective acids. The optimum experimental conditions for the preparation of 2-chloroacetyl-10-acetyl-phenothiazine by Friedel-Crafts reaction were studied. Also N-chloroacetyl-o-aminophenol was synthesized in high yield by a simple method. The preliminary pharmacological screening showed that two of these compounds possess a low order of tranquillizing activity.", "contents": "Synthesis of some new phenothiazine derivatives of expected medicinal value. 2-Chloroacetyl phenothiazines were reacted with certain phenols and salts of some acids under different conditions to yield 2-substituted acetylphenothiazines. Another series of 10-substituted phenothiazines was synthesized by treatment of 10-chloroacetylphenothiazine with either the appropriate amines or salts of the respective acids. The optimum experimental conditions for the preparation of 2-chloroacetyl-10-acetyl-phenothiazine by Friedel-Crafts reaction were studied. Also N-chloroacetyl-o-aminophenol was synthesized in high yield by a simple method. The preliminary pharmacological screening showed that two of these compounds possess a low order of tranquillizing activity."}
{"id": "PMID:3810", "title": "Morphological changes in the thymus of young and adult red-billed queleas Quelea quelea (aves).", "content": "In a wild population of red-billed queleas Quelea quelea L. (Ploceidae: weaver-birds) sampled throughout the year in East Africa, the thymus was found to enlarge in young birds shortly after hatching, remain enlarged during the juvenile stage, and regress towards the end of the postjuvenile moult. In adults, recrudescence occurred in many individuals during the prenuptial and postnuptial moults, and also in most if not all individuals, of both sexes, for a brief period during a breeding session. Thymus enlargement in both young and adults has been found to be accompanied by marked erythropoietic activity within the gland, and it is suggested that this activity is related to an increased demand for erythrocytes which may occur during moult and breeding.", "contents": "Morphological changes in the thymus of young and adult red-billed queleas Quelea quelea (aves). In a wild population of red-billed queleas Quelea quelea L. (Ploceidae: weaver-birds) sampled throughout the year in East Africa, the thymus was found to enlarge in young birds shortly after hatching, remain enlarged during the juvenile stage, and regress towards the end of the postjuvenile moult. In adults, recrudescence occurred in many individuals during the prenuptial and postnuptial moults, and also in most if not all individuals, of both sexes, for a brief period during a breeding session. Thymus enlargement in both young and adults has been found to be accompanied by marked erythropoietic activity within the gland, and it is suggested that this activity is related to an increased demand for erythrocytes which may occur during moult and breeding."}
{"id": "PMID:3811", "title": "Histological changes associated with enlargement and regression of the thymus glands of the red-billed quelea Quelea quelea L. (Ploceidae: weaver-birds).", "content": "Thymic lobes form over 200 red-billed queleas, Quelea quelea L., were examined histologically. Samples were taken from embryos about to hatch, juveniles and adults. The lobes varied in size from very small to very enlarged (1- greater than 5 mm long). The constituent cell types are described in detail and the occurrence of these cells in different sized lobes is discussed. A cycle of events is proposed which accounts for the observations presented here. It is suggested that the large numbers of erythroid cells found in the cortex of some individuals were developing in situ. The significance of erythropoiesis within the thymus is discussed.", "contents": "Histological changes associated with enlargement and regression of the thymus glands of the red-billed quelea Quelea quelea L. (Ploceidae: weaver-birds). Thymic lobes form over 200 red-billed queleas, Quelea quelea L., were examined histologically. Samples were taken from embryos about to hatch, juveniles and adults. The lobes varied in size from very small to very enlarged (1- greater than 5 mm long). The constituent cell types are described in detail and the occurrence of these cells in different sized lobes is discussed. A cycle of events is proposed which accounts for the observations presented here. It is suggested that the large numbers of erythroid cells found in the cortex of some individuals were developing in situ. The significance of erythropoiesis within the thymus is discussed."}
{"id": "PMID:3812", "title": "EMMA-4 analysis of iron in cells of the thymic cortex of a weaver-bird (Quelea quelea).", "content": "Combined morphological and analytical studies with the EMMA-4 analytical electron microscope have enabled very early erythroid cells to be identified within the cortex of enlarging thymic lobes of Quelea quelea. These early erythroid cells have pale cytoplasm (sometimes with ferritin-like crystals present), slightly pachychromatic nuclei and have fewer cell organelles (mitochondria) than lymphocytes. Counts for iron were approximately 70% lower than counts from mature erythrocytes found free in the cortex. Iron was also recorded from some epithelial reticular cells and pyknotic nuclei; no iron was recorded from small lymphocytes (thymocytes) in the cortex. The presence of very early erythroid cells is a further indication that erythropoiesis occurs in situ in the avian thymus.", "contents": "EMMA-4 analysis of iron in cells of the thymic cortex of a weaver-bird (Quelea quelea). Combined morphological and analytical studies with the EMMA-4 analytical electron microscope have enabled very early erythroid cells to be identified within the cortex of enlarging thymic lobes of Quelea quelea. These early erythroid cells have pale cytoplasm (sometimes with ferritin-like crystals present), slightly pachychromatic nuclei and have fewer cell organelles (mitochondria) than lymphocytes. Counts for iron were approximately 70% lower than counts from mature erythrocytes found free in the cortex. Iron was also recorded from some epithelial reticular cells and pyknotic nuclei; no iron was recorded from small lymphocytes (thymocytes) in the cortex. The presence of very early erythroid cells is a further indication that erythropoiesis occurs in situ in the avian thymus."}
{"id": "PMID:3813", "title": "The postcranial skeletons of the Triassic mammals Eozostrodon, Megazostrodon and Erythrotherium.", "content": "The purposes of this monograph are to describe the postcranial skeletons of the earliest known mammals, and to probe, in so far as possible by osteological study, biological questions concerning the habits and adaptations of these late Triassic forms. In this context, information on the background of this investigation is useful. Studies of Mesozoic mammals, begun some 150 years ago, are based on rare and fragmentary fossils, principally jaws and teeth. These investigations have yielded a bare outline of some 120 million years of mammalian evolution-about two-thirds of mammalian history. No assessment of the important biological changes occurring during this time can ever be complete, but major advances are possible as new discoveries provide material that is more complete or that represents a previously unknown evolutionary stage. So tenuous is the evidence that at least some concepts are re-evaluated with each discovery. Postcranial anatomy offers especially intriguing prospects for investigation because associated material (that can be positively assigned to a taxon below subclass) has been for the most part unknown, and indeed even dissociated bones are a rarity. Since G.G. Simpson's monographs of 1928 and 1929, progress in the study of Mesozoic mammals has been largely dependent on new finds. A major impetus to renewed investigation came from the discoveries of Mesozoic mammals by Walter K\u00fchne in 1939 and during the immediate post-war years. K\u00fchne first worked on fissures in the Carboniferous limestone quarries at Frome, Somerset, in southwest England where he collected a series of teeth of the problematical form Haramiya and two triconodont teeth which were placed in the genus Eozostrodon (Parrington 1941, 1946). The fissure faunas are generally thought to be of Upper Triassic (Rhaetic) age (K\u00fchne 1946), although Kermack, Musset & Rigney (1973) believe that the evidence is insufficient to determine whether the deposits are Rhaetic or Lower Liassic. After the war K\u00fchne carried his explorations farther west, eventually reaching the quarries at Bridgend in Glamorgan, Wales, where he not only found more triconodont teeth in some quantity (K\u00fchne 1958) but also a symmetrodont tooth (K\u00fchne 1950). Shortly after making these discoveries, K\u00fchne returned to Germany and the work was continued by a team from University College, London, under the leadership of Dr K.A. Kermack.", "contents": "The postcranial skeletons of the Triassic mammals Eozostrodon, Megazostrodon and Erythrotherium. The purposes of this monograph are to describe the postcranial skeletons of the earliest known mammals, and to probe, in so far as possible by osteological study, biological questions concerning the habits and adaptations of these late Triassic forms. In this context, information on the background of this investigation is useful. Studies of Mesozoic mammals, begun some 150 years ago, are based on rare and fragmentary fossils, principally jaws and teeth. These investigations have yielded a bare outline of some 120 million years of mammalian evolution-about two-thirds of mammalian history. No assessment of the important biological changes occurring during this time can ever be complete, but major advances are possible as new discoveries provide material that is more complete or that represents a previously unknown evolutionary stage. So tenuous is the evidence that at least some concepts are re-evaluated with each discovery. Postcranial anatomy offers especially intriguing prospects for investigation because associated material (that can be positively assigned to a taxon below subclass) has been for the most part unknown, and indeed even dissociated bones are a rarity. Since G.G. Simpson's monographs of 1928 and 1929, progress in the study of Mesozoic mammals has been largely dependent on new finds. A major impetus to renewed investigation came from the discoveries of Mesozoic mammals by Walter K\u00fchne in 1939 and during the immediate post-war years. K\u00fchne first worked on fissures in the Carboniferous limestone quarries at Frome, Somerset, in southwest England where he collected a series of teeth of the problematical form Haramiya and two triconodont teeth which were placed in the genus Eozostrodon (Parrington 1941, 1946). The fissure faunas are generally thought to be of Upper Triassic (Rhaetic) age (K\u00fchne 1946), although Kermack, Musset & Rigney (1973) believe that the evidence is insufficient to determine whether the deposits are Rhaetic or Lower Liassic. After the war K\u00fchne carried his explorations farther west, eventually reaching the quarries at Bridgend in Glamorgan, Wales, where he not only found more triconodont teeth in some quantity (K\u00fchne 1958) but also a symmetrodont tooth (K\u00fchne 1950). Shortly after making these discoveries, K\u00fchne returned to Germany and the work was continued by a team from University College, London, under the leadership of Dr K.A. Kermack."}
{"id": "PMID:3815", "title": "Classical conditioning in the sea anemone, Cribrina xanthogrammica.", "content": "Earlier attempts to classically condition sea anemones have yielded inconclusive results. Using light as CS and shock as US, conditioning as distinguished from sensitization and pseudoconditioning was demonstrated in anemones. Procedural controls included substitution of light alone, shock alone, and random light and shock in place of paired light-shock trials. Responses measured were electrical output and folding of the oral disc. The conditioned response was distinguished from the unconditioned response to light and the unconditioned response to shock in terms of response latency of both electrical and behavioral measures.", "contents": "Classical conditioning in the sea anemone, Cribrina xanthogrammica. Earlier attempts to classically condition sea anemones have yielded inconclusive results. Using light as CS and shock as US, conditioning as distinguished from sensitization and pseudoconditioning was demonstrated in anemones. Procedural controls included substitution of light alone, shock alone, and random light and shock in place of paired light-shock trials. Responses measured were electrical output and folding of the oral disc. The conditioned response was distinguished from the unconditioned response to light and the unconditioned response to shock in terms of response latency of both electrical and behavioral measures."}
{"id": "PMID:3816", "title": "Performance enhancement effects of d-amphetamine, methylphenidate, pipradrol and phenindamine in rats.", "content": "A multiple behavioral schedule with food reinforcement was designed to measure the drug-induced performance enhancement and non-effective activity in rats. The schedule, 20 min in duration, had CRF components in the 33 trials and extinction components in the inter-trial periods. During each trial, food reinforcement was present in the limited period (8 sec each) which was preceded by a discriminative stimulus (1 sec, either a light or a footshock). The rats generated a high rate of lever pressing during the limited period and a low rate of lever pressing during the inter-trial period. The drugs studied were d-amphetamine, methylphenidate, pipradrol and phenindamine. At low dosages, these drugs increased further the high rate of lever pressing. This was considered to be the performance enhancement effect. At higher doses, the drugs increased the low rate of lever pressing, decreased the high rate of lever pressing, and decreased responding of the rats to the discriminative stimulus. This latter pattern was considered to be the non-effective activity caused by the drugs. As expected, d-amphetamine was the most potent. Minor differences in drug effects were seen between the group of rats having light and that group having footshock as discriminative stimulus.", "contents": "Performance enhancement effects of d-amphetamine, methylphenidate, pipradrol and phenindamine in rats. A multiple behavioral schedule with food reinforcement was designed to measure the drug-induced performance enhancement and non-effective activity in rats. The schedule, 20 min in duration, had CRF components in the 33 trials and extinction components in the inter-trial periods. During each trial, food reinforcement was present in the limited period (8 sec each) which was preceded by a discriminative stimulus (1 sec, either a light or a footshock). The rats generated a high rate of lever pressing during the limited period and a low rate of lever pressing during the inter-trial period. The drugs studied were d-amphetamine, methylphenidate, pipradrol and phenindamine. At low dosages, these drugs increased further the high rate of lever pressing. This was considered to be the performance enhancement effect. At higher doses, the drugs increased the low rate of lever pressing, decreased the high rate of lever pressing, and decreased responding of the rats to the discriminative stimulus. This latter pattern was considered to be the non-effective activity caused by the drugs. As expected, d-amphetamine was the most potent. Minor differences in drug effects were seen between the group of rats having light and that group having footshock as discriminative stimulus."}
{"id": "PMID:3821", "title": "[Automatic method for determination of serum antistreptolysin].", "content": "The AA. describe a method of determination of serum antistreptolysin employing \"Technicon\" AutoAnalyzer, this method permitting the execution of 40 determinations in an hour, with a time of analysis of about 16 minutes. The procedure of analysis is very easy, with a very high selectivity of values; a variation coefficient of 5,3% and an accuracy index of 4,4% were found. Since the amount of serum employed is 50 mul this method appears to be particularly suitable in paediatry and in serological screening.", "contents": "[Automatic method for determination of serum antistreptolysin]. The AA. describe a method of determination of serum antistreptolysin employing \"Technicon\" AutoAnalyzer, this method permitting the execution of 40 determinations in an hour, with a time of analysis of about 16 minutes. The procedure of analysis is very easy, with a very high selectivity of values; a variation coefficient of 5,3% and an accuracy index of 4,4% were found. Since the amount of serum employed is 50 mul this method appears to be particularly suitable in paediatry and in serological screening."}
{"id": "PMID:3823", "title": "On the influence of prostaglandin F2alpha-induced labor at term on the metabolism and coagulation of mother and fetus.", "content": "11 pregnancies at term were terminated by dilatation of the uterine cervix, low amniotomy, and by intravenous administration of PGF2alpha. The average infusion time was 3 hours 55 minutes, and the average total dose of PGF2alpha amounted to 2.0 mg. Parameters of acid-base changes, carbohydrate and energic state changes, gas metabolism, and changes in coagulation and fibrinolysis in mother and in fetus were analyzed during labor and after birth. Labor activity and fetal cardiac action were monitored cardiotocographically. Checked against 50 uncomplicated spontaneous deliveries, we found no disadvantageous changes in the parameters investigated.", "contents": "On the influence of prostaglandin F2alpha-induced labor at term on the metabolism and coagulation of mother and fetus. 11 pregnancies at term were terminated by dilatation of the uterine cervix, low amniotomy, and by intravenous administration of PGF2alpha. The average infusion time was 3 hours 55 minutes, and the average total dose of PGF2alpha amounted to 2.0 mg. Parameters of acid-base changes, carbohydrate and energic state changes, gas metabolism, and changes in coagulation and fibrinolysis in mother and in fetus were analyzed during labor and after birth. Labor activity and fetal cardiac action were monitored cardiotocographically. Checked against 50 uncomplicated spontaneous deliveries, we found no disadvantageous changes in the parameters investigated."}
{"id": "PMID:3824", "title": "Pulmonary microembolism: attenuated pulmonary vasoconstriction with prostaglandin inhibitors and antihistamines.", "content": "The mechanism(s) involved in the pulmonary vascular and airway responses to pulmonary microembolism have not been clearly defined. Therefore, we determined the effects of specific prostaglandin and histamine blockade on the hemodynamic and arterial blood gas tension responses to particulate microembolism (200 mu glass beads) in intact anesthetized dogs. The marked increases in pulmonary arterial pressure and pulmonary vascular resistance observed in the untreated dogs were attenuated, but not abolished, following both prostaglandin blockade (with either meclofenamate or polyphloretin phosphate) and histamine blockade (with chlorpheniramine and metiamide) at 5 minutes, and were still attenuated 30 minutes post embolization. Combined prostaglandin and histamine blockade further attenuated, but again did not abolish, the pulmonary vascular responses. Cardiac outputs and systemic arterial pressures were unchanged from control by embolism. The alveolar hypoventilation (decreased arterial oxygen tension and increased carbon dioxide tension) observed in the untreated embolized dogs was prevented only with the prostaglandin inhibitors. Pulmonary microembolism in intact dogs, therefore, appears to induce vasoconstriction mediated partially by prostaglandin and histamine action, and alveolar hypoventilation mediated by prostaglandin, but not histamine, action.", "contents": "Pulmonary microembolism: attenuated pulmonary vasoconstriction with prostaglandin inhibitors and antihistamines. The mechanism(s) involved in the pulmonary vascular and airway responses to pulmonary microembolism have not been clearly defined. Therefore, we determined the effects of specific prostaglandin and histamine blockade on the hemodynamic and arterial blood gas tension responses to particulate microembolism (200 mu glass beads) in intact anesthetized dogs. The marked increases in pulmonary arterial pressure and pulmonary vascular resistance observed in the untreated dogs were attenuated, but not abolished, following both prostaglandin blockade (with either meclofenamate or polyphloretin phosphate) and histamine blockade (with chlorpheniramine and metiamide) at 5 minutes, and were still attenuated 30 minutes post embolization. Combined prostaglandin and histamine blockade further attenuated, but again did not abolish, the pulmonary vascular responses. Cardiac outputs and systemic arterial pressures were unchanged from control by embolism. The alveolar hypoventilation (decreased arterial oxygen tension and increased carbon dioxide tension) observed in the untreated embolized dogs was prevented only with the prostaglandin inhibitors. Pulmonary microembolism in intact dogs, therefore, appears to induce vasoconstriction mediated partially by prostaglandin and histamine action, and alveolar hypoventilation mediated by prostaglandin, but not histamine, action."}
{"id": "PMID:3828", "title": "Carotid body control of coronary flow, myocardial oxidative metabolism, and cardiac catecholamines in the dog.", "content": "In a series of 11 dogs, selective stimulation of the carotid body receptors by hypoxic, hypercapnic, acidotic blood produces bradycardia, an increase of coronary flow, and greater release of norepinephrine from the heart; the coronary resistances are decreased. The same stimulation after vagotomy is no longer accompanied by bradycardia; the decrease of coronary resistance is less marked and the release of norephinephrine is increased.", "contents": "Carotid body control of coronary flow, myocardial oxidative metabolism, and cardiac catecholamines in the dog. In a series of 11 dogs, selective stimulation of the carotid body receptors by hypoxic, hypercapnic, acidotic blood produces bradycardia, an increase of coronary flow, and greater release of norepinephrine from the heart; the coronary resistances are decreased. The same stimulation after vagotomy is no longer accompanied by bradycardia; the decrease of coronary resistance is less marked and the release of norephinephrine is increased."}
{"id": "PMID:3831", "title": "Noradrenergic subsensitivity of rat liver homogenates during chronic ethanol ingestion.", "content": "Prior studies indicated that chronic ethanol feeding induced noradrenergic subsensitivity of the cerebral cortex. Sensitivity was measured using the cAMP response of brain slices to norepinephrine (NE). In the present report we investigated the possibility that noradrenergic receptors in a visceral organ might be similarly affected by ethanol feeding. The cAMP response of liver homogenates to NE was measured. Chronic ethanol ingestion induced subsensitivity of the liver to NE similar to that observed in the brain. The ED50 was shifted to the right from 2.1 X 10(-5) M to 1.3 X 10(-4) M NE. By 3 days of ethanol withdrawal the cAMP response returned to control levels.", "contents": "Noradrenergic subsensitivity of rat liver homogenates during chronic ethanol ingestion. Prior studies indicated that chronic ethanol feeding induced noradrenergic subsensitivity of the cerebral cortex. Sensitivity was measured using the cAMP response of brain slices to norepinephrine (NE). In the present report we investigated the possibility that noradrenergic receptors in a visceral organ might be similarly affected by ethanol feeding. The cAMP response of liver homogenates to NE was measured. Chronic ethanol ingestion induced subsensitivity of the liver to NE similar to that observed in the brain. The ED50 was shifted to the right from 2.1 X 10(-5) M to 1.3 X 10(-4) M NE. By 3 days of ethanol withdrawal the cAMP response returned to control levels."}
{"id": "PMID:3832", "title": "Interactions between drugs and saliva-stimulating parafilm and their implications in measurements of saliva drug levels.", "content": "The interaction between Parafilm and four tranquilizers in their neutral phosphate buffer solutions resulted in various degrees of loss of the drugs from the solutions. The values of loss ranged from 15 to 34% for chlorpromazine and 8 to 42% for butaperazine at the initial concentration range of 2 to 20 mug/ml at room temperature (22 +/- 1 degree C). Under the same conditions, the values of loss from saliva for these two drugs were fairly constant; about 25% and 17%, respectively. For diazepam and chlordiazepoxide, the losses from the buffer solution were below 5%.", "contents": "Interactions between drugs and saliva-stimulating parafilm and their implications in measurements of saliva drug levels. The interaction between Parafilm and four tranquilizers in their neutral phosphate buffer solutions resulted in various degrees of loss of the drugs from the solutions. The values of loss ranged from 15 to 34% for chlorpromazine and 8 to 42% for butaperazine at the initial concentration range of 2 to 20 mug/ml at room temperature (22 +/- 1 degree C). Under the same conditions, the values of loss from saliva for these two drugs were fairly constant; about 25% and 17%, respectively. For diazepam and chlordiazepoxide, the losses from the buffer solution were below 5%."}
{"id": "PMID:3847", "title": "Acid hydrolases in the odontoblast-predentin region of dentinogenically active teeth.", "content": "The presence of hyaluronoglucosidase (EC 3.2.1.35; hyaluronidase), beta-N-acetylglucosaminidase (EC 3.2.1.30), exo-1,4-beta-xylosidase (EC 3.2.1.37), and arylsulfatase (EC 3.1.6.1) in dentinogenically active odontoblasts isolated from the rat incisor has been demonstrated by means of biochemical methods. The possible function of these enzymes in relation to the calcification process is discussed.", "contents": "Acid hydrolases in the odontoblast-predentin region of dentinogenically active teeth. The presence of hyaluronoglucosidase (EC 3.2.1.35; hyaluronidase), beta-N-acetylglucosaminidase (EC 3.2.1.30), exo-1,4-beta-xylosidase (EC 3.2.1.37), and arylsulfatase (EC 3.1.6.1) in dentinogenically active odontoblasts isolated from the rat incisor has been demonstrated by means of biochemical methods. The possible function of these enzymes in relation to the calcification process is discussed."}
{"id": "PMID:3848", "title": "N-acetyl-beta-D-hexosaminidase system in synovial fluid.", "content": "The present study was undertaken with the object of examining the N-Acetyl-beta-D-hexosaminidase activity in joint effusions from non-inflammatory (osteoarthrosis) and inflammatory (rheumatoid arthritis, gouty arthritis and chondrocalcinosis) joint diseases. The biochemical properties of four purified molecular forms were investigated. They were separated on the basis of their net charge, using DEAE-cellulose anion-exchangers. In the order of their outcome from the anion exchanger the four enzymes (B, I1, I2 and A) were found to have pH optima at 4.5-4.75, 4.20, 4.00 and 4.75, respectively. The first three enzymes proved to be heat-stable and the fourth enzyme fraction was a heat-labile form. By means of gel-filtration techniques, the enzymes were eluted into two fractions. The first contained the thermolabile A form and the molecular weight of this enzyme was estimated at 162000. The second fraction included the three thermostable enzymes. Their molecular weight was estimated at 135000. As described by Ikonne & Ellis (6) the hexosaminidase A from sera was less tightly held by the anion-exchanger than was the hexosaminidase A from tissues (polymorphonuclear cells, synovial membrane tissue, cartilage). Thus the serum type (As) must be distinct from the tissue type (At). The activity of the tissue type probably originating from the leukocytes and from the synovial membrane was more pronounced in the synovial effusions of the patients with inflammatory joint diseases. The hexosaminidase A fraction from synovial fluids of patients with osteoarthrosis contained only the serum type of enzyme.", "contents": "N-acetyl-beta-D-hexosaminidase system in synovial fluid. The present study was undertaken with the object of examining the N-Acetyl-beta-D-hexosaminidase activity in joint effusions from non-inflammatory (osteoarthrosis) and inflammatory (rheumatoid arthritis, gouty arthritis and chondrocalcinosis) joint diseases. The biochemical properties of four purified molecular forms were investigated. They were separated on the basis of their net charge, using DEAE-cellulose anion-exchangers. In the order of their outcome from the anion exchanger the four enzymes (B, I1, I2 and A) were found to have pH optima at 4.5-4.75, 4.20, 4.00 and 4.75, respectively. The first three enzymes proved to be heat-stable and the fourth enzyme fraction was a heat-labile form. By means of gel-filtration techniques, the enzymes were eluted into two fractions. The first contained the thermolabile A form and the molecular weight of this enzyme was estimated at 162000. The second fraction included the three thermostable enzymes. Their molecular weight was estimated at 135000. As described by Ikonne & Ellis (6) the hexosaminidase A from sera was less tightly held by the anion-exchanger than was the hexosaminidase A from tissues (polymorphonuclear cells, synovial membrane tissue, cartilage). Thus the serum type (As) must be distinct from the tissue type (At). The activity of the tissue type probably originating from the leukocytes and from the synovial membrane was more pronounced in the synovial effusions of the patients with inflammatory joint diseases. The hexosaminidase A fraction from synovial fluids of patients with osteoarthrosis contained only the serum type of enzyme."}
{"id": "PMID:3849", "title": "[Gastroenterology yesterday and today].", "content": "In the 40 years since the foundation of the \"Schweizerische Gesellschaft fur Gastroenterologie\", medicine - and with it gastroenterology - have markedly changed. New diseases and syndromes have been discovered and others have disappeared. New knowledge in basic sciences influences progress in diagnosis and therapy. In diagnostic methods the most evident advances are fiberendoscopy, endophotography and biopsy, and progress in roentgenology and immunology. New drugs, new surgical methods and controlled trials have improved treatment. However, each advance has its drawbacks: the growing incidence of iatrogenic diseases, the overwhelming literature, the flood of congresses, the record-breaking mentality of many clinicians and the hunting and collecting instinct for \"interesting cases\". \"Medical art\", a notion difficult to define, is in danger of disappearing. It means a harmony of knowledge, skill experience, intuition and the predominant desire to help the patient. This means individualized medicine, which is only possible by sympathetic dialogue with the patient - not only by specialists in psychiatry or psychosomatics, but by every doctor. will be able to preserve medicine from inhumanity in spite of technology, rationalization and the computer?", "contents": "[Gastroenterology yesterday and today]. In the 40 years since the foundation of the \"Schweizerische Gesellschaft fur Gastroenterologie\", medicine - and with it gastroenterology - have markedly changed. New diseases and syndromes have been discovered and others have disappeared. New knowledge in basic sciences influences progress in diagnosis and therapy. In diagnostic methods the most evident advances are fiberendoscopy, endophotography and biopsy, and progress in roentgenology and immunology. New drugs, new surgical methods and controlled trials have improved treatment. However, each advance has its drawbacks: the growing incidence of iatrogenic diseases, the overwhelming literature, the flood of congresses, the record-breaking mentality of many clinicians and the hunting and collecting instinct for \"interesting cases\". \"Medical art\", a notion difficult to define, is in danger of disappearing. It means a harmony of knowledge, skill experience, intuition and the predominant desire to help the patient. This means individualized medicine, which is only possible by sympathetic dialogue with the patient - not only by specialists in psychiatry or psychosomatics, but by every doctor. will be able to preserve medicine from inhumanity in spite of technology, rationalization and the computer?"}
{"id": "PMID:3851", "title": "Sperm diaphorase: genetic polymorphism of a sperm-specific enzyme in man.", "content": "Human sperm contains en enzyme with diaphorase activity that appears to be unique to sperm. Electrophoretic analysis of the diaphorase activity in sperm of different individuals reveals three phenotypic patterns. This polymorphism can be explained in terms of two alleles segregating at an autosomal locus; the allele frequencies have been determined to be 0.71 and 0.29. This appears to be the first reported example of a sperm-specific genetic polymorphism in man; its existence raises a number of genetic and biochemical questions.", "contents": "Sperm diaphorase: genetic polymorphism of a sperm-specific enzyme in man. Human sperm contains en enzyme with diaphorase activity that appears to be unique to sperm. Electrophoretic analysis of the diaphorase activity in sperm of different individuals reveals three phenotypic patterns. This polymorphism can be explained in terms of two alleles segregating at an autosomal locus; the allele frequencies have been determined to be 0.71 and 0.29. This appears to be the first reported example of a sperm-specific genetic polymorphism in man; its existence raises a number of genetic and biochemical questions."}
{"id": "PMID:3852", "title": "Acid precipitation and embryonic mortality of spotted salamanders, Ambystoma maculatum.", "content": "Spotted salamanders breed in temporary pools formed in early spring by melted snow and rain. Many of these pools reflect the low pH of precipitation in the northeastern United States. Egg mortality is low (less than 1 percent) in pools near neutrality, but high (greater than 60 percent) in pools more acid than pH 6. Developmental anomalies and the embryonic stage at which death occurs are the same in field situations as at corresponding pH's in laboratory experiments.", "contents": "Acid precipitation and embryonic mortality of spotted salamanders, Ambystoma maculatum. Spotted salamanders breed in temporary pools formed in early spring by melted snow and rain. Many of these pools reflect the low pH of precipitation in the northeastern United States. Egg mortality is low (less than 1 percent) in pools near neutrality, but high (greater than 60 percent) in pools more acid than pH 6. Developmental anomalies and the embryonic stage at which death occurs are the same in field situations as at corresponding pH's in laboratory experiments."}
{"id": "PMID:3853", "title": "Antibodies to histones and histone-histone complexes: immunochemical evidence for secondary structure in histone 1.", "content": "Highly specific antibodies were raised to histone 1 (H 1) and the histone complexes H32-H42 AND H2A-H2B, isolated by salt extraction. Antibody to H1 could detect irreversible conformational changes in acid- or urea-treated H1. The antibodies showed different reactivities with chromosomes as compared to antibodies in acid-extracted histones and should be useful in studies of native chromatin and chromosome structure.", "contents": "Antibodies to histones and histone-histone complexes: immunochemical evidence for secondary structure in histone 1. Highly specific antibodies were raised to histone 1 (H 1) and the histone complexes H32-H42 AND H2A-H2B, isolated by salt extraction. Antibody to H1 could detect irreversible conformational changes in acid- or urea-treated H1. The antibodies showed different reactivities with chromosomes as compared to antibodies in acid-extracted histones and should be useful in studies of native chromatin and chromosome structure."}
{"id": "PMID:3854", "title": "Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs.", "content": "Tritiated haloperidol and tritiated dopamine label postsynaptic dopamine receptors in mammalian brain. Clinical potencies of butyrophenones, phenothiazines, and related drugs correlate closely with their ability to inhibit tritiated haloperidol binding. These binding methods provide a simple in vitro means for evaluating new drugs as potential antischizophrenic agents.", "contents": "Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Tritiated haloperidol and tritiated dopamine label postsynaptic dopamine receptors in mammalian brain. Clinical potencies of butyrophenones, phenothiazines, and related drugs correlate closely with their ability to inhibit tritiated haloperidol binding. These binding methods provide a simple in vitro means for evaluating new drugs as potential antischizophrenic agents."}
{"id": "PMID:3855", "title": "Vector control of filariasis in the Solomon Islands.", "content": "In Solomon Islands, filariasis is caused by the nocturnally perodic form of Wuchereria bancrofti and is transmitted by the same vectors of malaria. This study explores the control of this disease as an additional effect of the Malaria Eradication Programme.", "contents": "Vector control of filariasis in the Solomon Islands. In Solomon Islands, filariasis is caused by the nocturnally perodic form of Wuchereria bancrofti and is transmitted by the same vectors of malaria. This study explores the control of this disease as an additional effect of the Malaria Eradication Programme."}
{"id": "PMID:3857", "title": "Standardisation of the preparation of platelet concentrates.", "content": "Platelet concentrates with a yield of 80,8% and an absolute number of platelets per pack of 0,86 X 10(11) were obtained, using an optimised harvesting method. This method involved standardised collection of whole blood with constant mixing of blood and anticoagulant, a first centrifugation at 750 g for 6 minutes at 22 degrees C (full brake) and a second centrifugation at 2 0000 g for 20 minutes at 22 degrees C (half brake). Resuspension of the platelet pellet in plasma was effected by leaving the pack at room temperature for 30 minutes. Platelet concentrates of 25 ml and 50 ml volume displayed satisfactory pH and count characteristics after 72-hour storage both at room temperature and at 2 - 10 degrees C.", "contents": "Standardisation of the preparation of platelet concentrates. Platelet concentrates with a yield of 80,8% and an absolute number of platelets per pack of 0,86 X 10(11) were obtained, using an optimised harvesting method. This method involved standardised collection of whole blood with constant mixing of blood and anticoagulant, a first centrifugation at 750 g for 6 minutes at 22 degrees C (full brake) and a second centrifugation at 2 0000 g for 20 minutes at 22 degrees C (half brake). Resuspension of the platelet pellet in plasma was effected by leaving the pack at room temperature for 30 minutes. Platelet concentrates of 25 ml and 50 ml volume displayed satisfactory pH and count characteristics after 72-hour storage both at room temperature and at 2 - 10 degrees C."}
{"id": "PMID:3858", "title": "Suppression of postpartum lactation with furosemide.", "content": "A regimen of fursemide and moderate restriction of fluid intake was followed in 120 postpartum women to suppress lactation. The methods and results are presented, and possible mechanisms whereby furosemide may suppress lactation are discussed.", "contents": "Suppression of postpartum lactation with furosemide. A regimen of fursemide and moderate restriction of fluid intake was followed in 120 postpartum women to suppress lactation. The methods and results are presented, and possible mechanisms whereby furosemide may suppress lactation are discussed."}
{"id": "PMID:3868", "title": "[Changes of protein metabolism following irradiation. II. Protease activity, protease pattern, protein and free amino acids in the cytoplasm and cell organelles of the rat liver following 600 R whole-body irradiation].", "content": "The protease activity of cytoplasm and cell organelles of the rat liver against liver protein and hemoglobin as a substrate increases during an initial reaction phase on the first day after 600 R whole body X-irradiation. This is probably a consequence of the degradation of cellular debris. The protein, the protease activity and the free amino acids of the cytoplasm and the cell organelles decrease during the disease phase on day 3 and 4 after irradiation. The protein loss of the liver is therefore not explained by an increased protease activity. The protease activity and the free amino acids are increased in the cytoplasm and the cell organelles during the regeneration phase of the organism between day 15 and 18 after irradiation.", "contents": "[Changes of protein metabolism following irradiation. II. Protease activity, protease pattern, protein and free amino acids in the cytoplasm and cell organelles of the rat liver following 600 R whole-body irradiation]. The protease activity of cytoplasm and cell organelles of the rat liver against liver protein and hemoglobin as a substrate increases during an initial reaction phase on the first day after 600 R whole body X-irradiation. This is probably a consequence of the degradation of cellular debris. The protein, the protease activity and the free amino acids of the cytoplasm and the cell organelles decrease during the disease phase on day 3 and 4 after irradiation. The protein loss of the liver is therefore not explained by an increased protease activity. The protease activity and the free amino acids are increased in the cytoplasm and the cell organelles during the regeneration phase of the organism between day 15 and 18 after irradiation."}
{"id": "PMID:3869", "title": "Dynamics of the changes in the tissular levels of cyclic AMP after cobalt-60 gamma-irradiation.", "content": "The total amounts of cyclic AMP in liver, brain and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation. This radiation, even in a lethal dose, was found to induce no significant changes in the hepatic levels of cAMP. In contrast, an abrupt short-lasting increase in the levels of cAMP was observed in brain and intestinal mucosa after a 500-rd-irradiation, and a progressive long-lasting increase in its levels in the intestinal mucosa and, especially, in the brain was found after a 750-rd-irradiation. It is concluded that these organs contain different cAMP systems, which would explain, at least in part, their dissimilar responses to the ionizing rays.", "contents": "Dynamics of the changes in the tissular levels of cyclic AMP after cobalt-60 gamma-irradiation. The total amounts of cyclic AMP in liver, brain and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation. This radiation, even in a lethal dose, was found to induce no significant changes in the hepatic levels of cAMP. In contrast, an abrupt short-lasting increase in the levels of cAMP was observed in brain and intestinal mucosa after a 500-rd-irradiation, and a progressive long-lasting increase in its levels in the intestinal mucosa and, especially, in the brain was found after a 750-rd-irradiation. It is concluded that these organs contain different cAMP systems, which would explain, at least in part, their dissimilar responses to the ionizing rays."}
{"id": "PMID:3871", "title": "Changes in the composition of milk and rumen contents in cows exposed to a high ambient temperature with controlled feeding.", "content": "Two pairs of Jersey cows were exposed to either 15 or 30 degrees C air temperature; intake of dried grass was controlled, to be equal at both temperatures. Exposure to 30 degrees C caused increases in rectal temperature and in respiratory rates, and decreases infood intakes in both cows. Milk yield decreased by similar amounts at both temperatures, in association with the decreases in food intakes. The fat and protein content of milk decreased significantly at 30 degrees C; the proportion of shorter chain fatty acids (C6-C14) IN THE milk fat also decreased at 30 degrees C. The proportion of acetic acid in the rumen contents decreased significantly at 30 degrees C, in association with a small decrease in pH. The results indicate that changes in the metabolism of cows occurred at 30 degrees C, independently of changes in food intake.", "contents": "Changes in the composition of milk and rumen contents in cows exposed to a high ambient temperature with controlled feeding. Two pairs of Jersey cows were exposed to either 15 or 30 degrees C air temperature; intake of dried grass was controlled, to be equal at both temperatures. Exposure to 30 degrees C caused increases in rectal temperature and in respiratory rates, and decreases infood intakes in both cows. Milk yield decreased by similar amounts at both temperatures, in association with the decreases in food intakes. The fat and protein content of milk decreased significantly at 30 degrees C; the proportion of shorter chain fatty acids (C6-C14) IN THE milk fat also decreased at 30 degrees C. The proportion of acetic acid in the rumen contents decreased significantly at 30 degrees C, in association with a small decrease in pH. The results indicate that changes in the metabolism of cows occurred at 30 degrees C, independently of changes in food intake."}
{"id": "PMID:3870", "title": "Brain microvascular hemodynamic responses to induced seizures.", "content": "Arteriolar diameters and venular erythrocyte velocities in the small pial vessels on the surface of the cat brain were measured by TV methods during induced epileptic seizures through a cranial window. Grand mal seizures maximally dilated arterioles and increased venular erythrocyte velocity up to 400%. High positive correlation existed between changes in CSF hydrogen ion concentration and pial arteriolar diameter, suggesting metabolic regulation of CBF through CSF/interstitial fluid hydrogen ion alterations during the seizure.", "contents": "Brain microvascular hemodynamic responses to induced seizures. Arteriolar diameters and venular erythrocyte velocities in the small pial vessels on the surface of the cat brain were measured by TV methods during induced epileptic seizures through a cranial window. Grand mal seizures maximally dilated arterioles and increased venular erythrocyte velocity up to 400%. High positive correlation existed between changes in CSF hydrogen ion concentration and pial arteriolar diameter, suggesting metabolic regulation of CBF through CSF/interstitial fluid hydrogen ion alterations during the seizure."}
{"id": "PMID:3872", "title": "[Characteristics of heterogeneity of serum albumin in heterosis-hybrid chickens].", "content": "A comparative study was performed for isoelectric and electrophoretic spectra blood serum albumin of parental breeds of chickens and their heterosis hybrids --broiler cocks. The method of isoelectric focusing within the surcrose density gradient and pH 4-6 created by the gradient of sucrose, mannitol and boron-borate buffer (pH 8.5) concentrations was applied. The electrophoretic spectrum of the serum albumin fraction homogeneous in the agar gel was obtained by electrophoresis in 7% polyacrylamide gel. The isoelectric spectrum of heterosis hybrid albumin is established to be more heterogeneous and during isoelectric focusing it is divided within a range of pH 4.6-5.2 into seven fractions against four-five components of the parent breed albumin. Among them it is possible to distinguish the fraction involving more than 50% of the total protein (the great component) and some small components with different protein content and belonging wither to a more acid or more basic region as compared to pI of the great component. The pI value of the great component for hybrid albumin is shifted towards the acid region (4.76 against 4.85 and 5.07 in albumin of the parent breeds). Small component of hybrid albumin are characterized by an increase in their amount, but pI of the fraction is within the range of values peculiar to albumin of the maternal and paternal lines. The albumin preparations of all the studied chicken breeds isolated from blood serum by electrophoresis in the agar gel manifest multiplicity of the protein bands in a 7% polyacrylamide gel. The electric spectra of hybrid albumin and parent breeds albumin differ in the distribution pattern of the components and their quantitative composition. A relative electrophoretic mobility of the intensively stained dense band which represents the main electrophoretic component is increased in hydrid albumin with the respect to albumin of the maternal line but is identical to the paternal line.", "contents": "[Characteristics of heterogeneity of serum albumin in heterosis-hybrid chickens]. A comparative study was performed for isoelectric and electrophoretic spectra blood serum albumin of parental breeds of chickens and their heterosis hybrids --broiler cocks. The method of isoelectric focusing within the surcrose density gradient and pH 4-6 created by the gradient of sucrose, mannitol and boron-borate buffer (pH 8.5) concentrations was applied. The electrophoretic spectrum of the serum albumin fraction homogeneous in the agar gel was obtained by electrophoresis in 7% polyacrylamide gel. The isoelectric spectrum of heterosis hybrid albumin is established to be more heterogeneous and during isoelectric focusing it is divided within a range of pH 4.6-5.2 into seven fractions against four-five components of the parent breed albumin. Among them it is possible to distinguish the fraction involving more than 50% of the total protein (the great component) and some small components with different protein content and belonging wither to a more acid or more basic region as compared to pI of the great component. The pI value of the great component for hybrid albumin is shifted towards the acid region (4.76 against 4.85 and 5.07 in albumin of the parent breeds). Small component of hybrid albumin are characterized by an increase in their amount, but pI of the fraction is within the range of values peculiar to albumin of the maternal and paternal lines. The albumin preparations of all the studied chicken breeds isolated from blood serum by electrophoresis in the agar gel manifest multiplicity of the protein bands in a 7% polyacrylamide gel. The electric spectra of hybrid albumin and parent breeds albumin differ in the distribution pattern of the components and their quantitative composition. A relative electrophoretic mobility of the intensively stained dense band which represents the main electrophoretic component is increased in hydrid albumin with the respect to albumin of the maternal line but is identical to the paternal line."}
{"id": "PMID:3876", "title": "Metomidate as sole anaesthetic agent in tawny owls.", "content": "Metomidate 1 per cent was administered intramuscularly as the sole anaesthetic agent on 22 occasions to seven tawny owls (Strix aluco). Four deaths occurred, none on the first administration. ECG findings and details of dosage are provided. The possible causes of death are discussed.", "contents": "Metomidate as sole anaesthetic agent in tawny owls. Metomidate 1 per cent was administered intramuscularly as the sole anaesthetic agent on 22 occasions to seven tawny owls (Strix aluco). Four deaths occurred, none on the first administration. ECG findings and details of dosage are provided. The possible causes of death are discussed."}
{"id": "PMID:3873", "title": "[Peculiarities of acid-base reserves in aging].", "content": "The age-dependent peculiarities of the acid-base balance at rest and with standard loads were studied in 466 rats. It was found that with age the pH value of blood decreases, the tension of the carbonic acid increases, but the values of BB, BE, SB, and AB do not undergo any significant changes. With loads, old animals showed more profound changes in the system and these changes were of decompensated character. The maximal changes in young animals were registered 1.5 hours after loading, in old rats--3 hours after. The normalization of the shifts in old rats occurred much more slowly than in young animals, and it does not reached the initial value by 24 hours after loading. The analysis of the data obtained shows that with aging the reserve potentialities of the organism's mechanisms of the acid-base balance regulation greatly decrease, which under certain conditions results in disturbance of the given system compensation, thus exerting a negative effect on the body vital processes.", "contents": "[Peculiarities of acid-base reserves in aging]. The age-dependent peculiarities of the acid-base balance at rest and with standard loads were studied in 466 rats. It was found that with age the pH value of blood decreases, the tension of the carbonic acid increases, but the values of BB, BE, SB, and AB do not undergo any significant changes. With loads, old animals showed more profound changes in the system and these changes were of decompensated character. The maximal changes in young animals were registered 1.5 hours after loading, in old rats--3 hours after. The normalization of the shifts in old rats occurred much more slowly than in young animals, and it does not reached the initial value by 24 hours after loading. The analysis of the data obtained shows that with aging the reserve potentialities of the organism's mechanisms of the acid-base balance regulation greatly decrease, which under certain conditions results in disturbance of the given system compensation, thus exerting a negative effect on the body vital processes."}
{"id": "PMID:3884", "title": "[Dynamics of production and various properties of interferon-like inhibitors formed under the influence of AET and cystaphos in vivo and in cell cultures].", "content": "Interferon-like virus inhibitors appeared in the blood serum of animals and in the culture fluid 15 min.--1 hour and 4-6 hours after administration of AET (S, beta-amino-ethylisotiuronium) and cystaphos (monosodium salt of beta-aminoethylthiophosphorus acid). These inhibitors showed species-specificity, were inactivated by trypsin and by heating at 37 degrees C for 2 hours and at 56 degrees C for 1 hour, did not sediment at 100,000 g. It is assumed that these are two different inhibitors of which the one forming the early peak pre-exists in the cell. It is probably associated with cell membranes and is released as a result of chemical effect of aminothyols. The late peak of inhibitor is synthesized de novo as inducated by its sensitivity to the effect of puromycin and cycloheximide.", "contents": "[Dynamics of production and various properties of interferon-like inhibitors formed under the influence of AET and cystaphos in vivo and in cell cultures]. Interferon-like virus inhibitors appeared in the blood serum of animals and in the culture fluid 15 min.--1 hour and 4-6 hours after administration of AET (S, beta-amino-ethylisotiuronium) and cystaphos (monosodium salt of beta-aminoethylthiophosphorus acid). These inhibitors showed species-specificity, were inactivated by trypsin and by heating at 37 degrees C for 2 hours and at 56 degrees C for 1 hour, did not sediment at 100,000 g. It is assumed that these are two different inhibitors of which the one forming the early peak pre-exists in the cell. It is probably associated with cell membranes and is released as a result of chemical effect of aminothyols. The late peak of inhibitor is synthesized de novo as inducated by its sensitivity to the effect of puromycin and cycloheximide."}
{"id": "PMID:3890", "title": "[Lipolysis in human adipose tissue (author's transl)].", "content": "Lipolytic activity was measured under different conditions in isolated fat cells and homogenates of human adipose tissue of the greater omentum. It was demonstrated that lipolysis took place in isolated fat cells at an optimum pH of 7.4 and was markedly stimulated by noradrenaline, but not by blood serum. By contrast lipolysis was significantly stimulated by blood serum, but not by noradrenaline, in homogenates of adipose tissue. Serum-stimulated lipolysis exhibited optimum activity at pH 8 and was inhibited by 1M sodium chloride. It is concluded that lipolytic activity in isolated fat cells can mainly be ascribed to the action of hormone-sensitive lipase, whereas lipolysis in homogenates of adipose tissue in the presence of serum is mostly regulated by lipoprotein lipase.", "contents": "[Lipolysis in human adipose tissue (author's transl)]. Lipolytic activity was measured under different conditions in isolated fat cells and homogenates of human adipose tissue of the greater omentum. It was demonstrated that lipolysis took place in isolated fat cells at an optimum pH of 7.4 and was markedly stimulated by noradrenaline, but not by blood serum. By contrast lipolysis was significantly stimulated by blood serum, but not by noradrenaline, in homogenates of adipose tissue. Serum-stimulated lipolysis exhibited optimum activity at pH 8 and was inhibited by 1M sodium chloride. It is concluded that lipolytic activity in isolated fat cells can mainly be ascribed to the action of hormone-sensitive lipase, whereas lipolysis in homogenates of adipose tissue in the presence of serum is mostly regulated by lipoprotein lipase."}
{"id": "PMID:3891", "title": "[Study of the influence of the beta-sympatholytic drug KO 1366 (Bunitrolol on lung function (author's transl)].", "content": "20 untreated outpatients suffering from chronic obstructive airway disease were tested with a new beta-sympatholytic agent, K\u00f6 1366 (bunitrolol) or placebo in a randomized symptoms of bronchitis, but hacetylcholine inhalation was followed by severe bronchospastic hyperreactivity. The intravenous administration of 2.5 mg K\u00f6 1366 resulted in a rapid and statistically significant (p less than 0.001) marked decrease in heart rate due to the beta-sympatholytic effect. Airway resistance, however, measured by whole-body plethysmography, was not affected. K\u00f6 1366 can be regarded as a cardio-selective beta-sympatholytic drug in so far as i.v. administration is possible in patients with airway disease during a non-obstructive period. Moreover, should a bronchospastic reaction occur immediate control by inhalation of adrenergic or vagolytic drugs is possible.", "contents": "[Study of the influence of the beta-sympatholytic drug KO 1366 (Bunitrolol on lung function (author's transl)]. 20 untreated outpatients suffering from chronic obstructive airway disease were tested with a new beta-sympatholytic agent, K\u00f6 1366 (bunitrolol) or placebo in a randomized symptoms of bronchitis, but hacetylcholine inhalation was followed by severe bronchospastic hyperreactivity. The intravenous administration of 2.5 mg K\u00f6 1366 resulted in a rapid and statistically significant (p less than 0.001) marked decrease in heart rate due to the beta-sympatholytic effect. Airway resistance, however, measured by whole-body plethysmography, was not affected. K\u00f6 1366 can be regarded as a cardio-selective beta-sympatholytic drug in so far as i.v. administration is possible in patients with airway disease during a non-obstructive period. Moreover, should a bronchospastic reaction occur immediate control by inhalation of adrenergic or vagolytic drugs is possible."}
{"id": "PMID:3892", "title": "[Cerebral manifestations in the hepatic coma syndrome (author's transl)].", "content": "The pathogenesis of hepatic encephalopathy has been investigated in a two-stage devascularization model in the rat with portavacal shunt and hepatic artery ligation. There is a significant increase in brain octopamine and phenylethanolamine and a decrease in brain norepinephrine (NE) 6 to 9 hours after hepatic artery ligation. The depletion of NE seems the sequel of diminished synthesis in the presence of an unaltered turnover rate, due to a blockade of tyrosine hydroxylase either by accumulation of false neurochemical transmitters or by phenylalanine. It is most marked in the cortex and midbrain. The high-energy phosphate compounds, ATP, phosphocreatine and glucose-6-phosphate are not diminished in hepatic coma, nor is glucose, indicating that other mechanism are involved in the pathogenesis of metabolic state by the increased ammonia level. \"intestinal sterilization\" and total colectomy have no significant effect on the ammonia level, but cause a decrease in the level or aromatic precursor amino acids in the plasma and brain, with normalization of the level of cerebral transmitters. These results permit the formulation of a unified concept of the hepatic coma syndrome and its clinical manifestations such as flapping tremor, the hyperdynamic cardiovascular state and the hepatorenal syndrome. Moreover, they form the basis for the introduction of a new therapeutic principle in the management of hepatic encephalopathy by L-dopa or modified amino acid solutions, which act by altering the central and peripheral neurotransmitters.", "contents": "[Cerebral manifestations in the hepatic coma syndrome (author's transl)]. The pathogenesis of hepatic encephalopathy has been investigated in a two-stage devascularization model in the rat with portavacal shunt and hepatic artery ligation. There is a significant increase in brain octopamine and phenylethanolamine and a decrease in brain norepinephrine (NE) 6 to 9 hours after hepatic artery ligation. The depletion of NE seems the sequel of diminished synthesis in the presence of an unaltered turnover rate, due to a blockade of tyrosine hydroxylase either by accumulation of false neurochemical transmitters or by phenylalanine. It is most marked in the cortex and midbrain. The high-energy phosphate compounds, ATP, phosphocreatine and glucose-6-phosphate are not diminished in hepatic coma, nor is glucose, indicating that other mechanism are involved in the pathogenesis of metabolic state by the increased ammonia level. \"intestinal sterilization\" and total colectomy have no significant effect on the ammonia level, but cause a decrease in the level or aromatic precursor amino acids in the plasma and brain, with normalization of the level of cerebral transmitters. These results permit the formulation of a unified concept of the hepatic coma syndrome and its clinical manifestations such as flapping tremor, the hyperdynamic cardiovascular state and the hepatorenal syndrome. Moreover, they form the basis for the introduction of a new therapeutic principle in the management of hepatic encephalopathy by L-dopa or modified amino acid solutions, which act by altering the central and peripheral neurotransmitters."}
{"id": "PMID:3893", "title": "[Urinary enzymes in the early detection of rejection reactions after renal transplantation (author's transl)].", "content": "Urinary enzymes were studied in 15 patients subjected to kidney transplantation. The investigation was initiated immediately after operation and was continued for a period of between 2 and 8 weeks. There was a significant increase in urinary MDH activity in 94.2% of cases, of LDH activity in 95,65% and of gamma-GT activity in 95,17% of the cases. This detected increase in urinary enzyme activities preceded the clinical diagnosis of rejection by activities preceded the clinical diagnosis of rejection by at least 24 hours. Determination of these enzymes provides a reliable tool for the early detection of rejection crises.", "contents": "[Urinary enzymes in the early detection of rejection reactions after renal transplantation (author's transl)]. Urinary enzymes were studied in 15 patients subjected to kidney transplantation. The investigation was initiated immediately after operation and was continued for a period of between 2 and 8 weeks. There was a significant increase in urinary MDH activity in 94.2% of cases, of LDH activity in 95,65% and of gamma-GT activity in 95,17% of the cases. This detected increase in urinary enzyme activities preceded the clinical diagnosis of rejection by activities preceded the clinical diagnosis of rejection by at least 24 hours. Determination of these enzymes provides a reliable tool for the early detection of rejection crises."}
{"id": "PMID:3889", "title": "[Extracardiac factors in the development of arrhythmias (author's transl)].", "content": "A brief survey is given of some of the most frequent extracardiac causes which may provoke disturbances of rhythm. The importance of psychogenic and metabolic factors is emphasized. Additional organic lesions cannot be excluded in every case.", "contents": "[Extracardiac factors in the development of arrhythmias (author's transl)]. A brief survey is given of some of the most frequent extracardiac causes which may provoke disturbances of rhythm. The importance of psychogenic and metabolic factors is emphasized. Additional organic lesions cannot be excluded in every case."}
{"id": "PMID:3895", "title": "[Inducible accumulation of alpha-ketoglutaric acid in cultures of Streptomyces hygroscopicus JA 6599 producing a macrolide antibiotic].", "content": "The excessive production of pyruvic and 2-oxoglutaric acid by S. hygroscopicus JA 6599 grown on a medium rich in complex carbon and nitrogen sources was studied. Towards the end of the first day of batch cultivation a maximum level of both keto acids in the medium was observed. By diluting the complete culture with water at 22nd hour, however, a further increase in 2-oxoglutarate concentration was induced and the antibiotic production was slightly stimulated. In diluted cultures the oxygen saturation was found to be distinctly higher than in non-diluted ones and, on the other hand, the mycelial activities of both pyruvate and 2-oxoglutarate decarboxylases were decreased. Since the 2-oxoglutarate level was strongly influenced by inhibitors of glycolysis and of citric acid cycle, it is suggested that the metabolite accumulation in diluted cultures is mainly caused by modifications of the metabolic control of carbohydrate catabolism due to an improved aeration. Furthermore, the macrolide antibiotic A 6599 produced by S. hygroscopicus JA 6599 itself was shown to interfere with the accumulation of 2-oxoglutaric acid.", "contents": "[Inducible accumulation of alpha-ketoglutaric acid in cultures of Streptomyces hygroscopicus JA 6599 producing a macrolide antibiotic]. The excessive production of pyruvic and 2-oxoglutaric acid by S. hygroscopicus JA 6599 grown on a medium rich in complex carbon and nitrogen sources was studied. Towards the end of the first day of batch cultivation a maximum level of both keto acids in the medium was observed. By diluting the complete culture with water at 22nd hour, however, a further increase in 2-oxoglutarate concentration was induced and the antibiotic production was slightly stimulated. In diluted cultures the oxygen saturation was found to be distinctly higher than in non-diluted ones and, on the other hand, the mycelial activities of both pyruvate and 2-oxoglutarate decarboxylases were decreased. Since the 2-oxoglutarate level was strongly influenced by inhibitors of glycolysis and of citric acid cycle, it is suggested that the metabolite accumulation in diluted cultures is mainly caused by modifications of the metabolic control of carbohydrate catabolism due to an improved aeration. Furthermore, the macrolide antibiotic A 6599 produced by S. hygroscopicus JA 6599 itself was shown to interfere with the accumulation of 2-oxoglutaric acid."}
{"id": "PMID:3898", "title": "[Immunosuppressive treatment in autoimmune vasculities].", "content": "From own experiences the observations of 3 patients were reported who were immunosuppressively treated with purine antagonists (azathioprine and 6-mercaptopurine). Hereby in a severe allergic vasculitis in a 22-year-old patient and in a granulomatous arteritis during Wegener's granulomatosis in a 51-year-old patient remissions for more than 1 and 7 years, respectively, could be achieved under immunosuppressive long-term therapy. In the case of a periarteriitis nodosa death took place 2 months after administration of 6-mercaptopurine.", "contents": "[Immunosuppressive treatment in autoimmune vasculities]. From own experiences the observations of 3 patients were reported who were immunosuppressively treated with purine antagonists (azathioprine and 6-mercaptopurine). Hereby in a severe allergic vasculitis in a 22-year-old patient and in a granulomatous arteritis during Wegener's granulomatosis in a 51-year-old patient remissions for more than 1 and 7 years, respectively, could be achieved under immunosuppressive long-term therapy. In the case of a periarteriitis nodosa death took place 2 months after administration of 6-mercaptopurine."}
{"id": "PMID:3899", "title": "[Possibilities and limits of the intrauterine reanimation (author's transl)].", "content": "Intrauterine reanimation means the removal of acute maternal or fetal distress. Beside of maternal shock (traumatic, hoaemorrhagic, supine hypotension syndrome) all acute distress situation are seen during labour. The therapeutical possibilities and premises on the one side, the limits and dangers on the other are discussed. There are the change of position in bed, infusion of low molecular dextrane, O2- breathing, buffering of the mother, infusion of vasodilatators and beta-stimulators to the mother. The main therapeutical principle for intrauterine reanimation are change of side position and beta-stimulator therapy in case of disturbances in feto-maternal respiration because of an acute utero-placental insufficiency or a cord complication. As to an own patient group with intrauterine reanimation with the beta-stimulator \"Partusisten\" in 174 deliveries with cardiotocographic signs of fetal distress in the first stage of labour there is shown that threatened fetal distress because of uterine hyperactivity and cord complication is successfully treated by tocolysis. In case of chronic placental insufficiency there is no therapeutical success by intra partum tocolysis in 30%.", "contents": "[Possibilities and limits of the intrauterine reanimation (author's transl)]. Intrauterine reanimation means the removal of acute maternal or fetal distress. Beside of maternal shock (traumatic, hoaemorrhagic, supine hypotension syndrome) all acute distress situation are seen during labour. The therapeutical possibilities and premises on the one side, the limits and dangers on the other are discussed. There are the change of position in bed, infusion of low molecular dextrane, O2- breathing, buffering of the mother, infusion of vasodilatators and beta-stimulators to the mother. The main therapeutical principle for intrauterine reanimation are change of side position and beta-stimulator therapy in case of disturbances in feto-maternal respiration because of an acute utero-placental insufficiency or a cord complication. As to an own patient group with intrauterine reanimation with the beta-stimulator \"Partusisten\" in 174 deliveries with cardiotocographic signs of fetal distress in the first stage of labour there is shown that threatened fetal distress because of uterine hyperactivity and cord complication is successfully treated by tocolysis. In case of chronic placental insufficiency there is no therapeutical success by intra partum tocolysis in 30%."}
{"id": "PMID:3900", "title": "Graft-versus-host reaction: a pathogenetic principle for the development of drug allergy, autoimmunity, and malignant lymphoma in non-chimeric individuals. Hypothesis.", "content": "It is proposed that the same diseases as those induced by the graft-versus-host reaction (GVHR) will arise in nonchimeric individuals, if structures of the major histocompatibility complex (MHC) on lymphocytes are altered, either by viral infection or by chemicals, in such a way that autologous T lymphocytes react against them as the react in the GVHR to semiallogeneic (F1) lymphocytes differing at the MHC. Diseases in which a GVHR-like pathogenesis is suspected will be discussed.", "contents": "Graft-versus-host reaction: a pathogenetic principle for the development of drug allergy, autoimmunity, and malignant lymphoma in non-chimeric individuals. Hypothesis. It is proposed that the same diseases as those induced by the graft-versus-host reaction (GVHR) will arise in nonchimeric individuals, if structures of the major histocompatibility complex (MHC) on lymphocytes are altered, either by viral infection or by chemicals, in such a way that autologous T lymphocytes react against them as the react in the GVHR to semiallogeneic (F1) lymphocytes differing at the MHC. Diseases in which a GVHR-like pathogenesis is suspected will be discussed."}
{"id": "PMID:3901", "title": "[Studies on the hatching of miracidia of Dicrocoelium dendriticum (author's transl)].", "content": "The eggs of Dicrocoelium dendriticum were induced to open by solutions of formic acid and caproic acid (Table 1). The miracidia hatched in O2-free water after the eggs had been dried with N2 or in vacuum. The miracidia were able to live for 3 hours if water contained 20 mM NaCl, 10 mM KCl, and 1 mM CaCl2. Ca++-ions are obviously necessary for the mobility of miracidia. The experimental use of intestinal juice of the Roman snail Helix pomatia gave hatching results which were dependent on the absence of O2 (exposure to N2) and the presence of bacteria with a still unknown function. The dependence on pH seems to be indirect (Abb. 2). Studies on the permeabilities of the egg shell and the embryonic membrane (\"vitelline membrane\"), the evidence of an oligosaccharide (Abb. 3) liberated from the \"spaltraum\" (Abb. 1) during egg-opening, and the determination of the osmotic pressure of the hatching process (50% hatching in 1.2--14. Osmols sucrose/1000 ml H2O; Abb. 4) led to the following hypothesis of hatching mechanism: After the activation of the granular gland of the miracidium an enzyme is released into the extra-embryonic \"spaltraum\". A polysaccharide is digested to an oligosaccharide which cannot permeate the egg shell and the embryonic membrane. The rising osmotic pressure bursts off the operculum.", "contents": "[Studies on the hatching of miracidia of Dicrocoelium dendriticum (author's transl)]. The eggs of Dicrocoelium dendriticum were induced to open by solutions of formic acid and caproic acid (Table 1). The miracidia hatched in O2-free water after the eggs had been dried with N2 or in vacuum. The miracidia were able to live for 3 hours if water contained 20 mM NaCl, 10 mM KCl, and 1 mM CaCl2. Ca++-ions are obviously necessary for the mobility of miracidia. The experimental use of intestinal juice of the Roman snail Helix pomatia gave hatching results which were dependent on the absence of O2 (exposure to N2) and the presence of bacteria with a still unknown function. The dependence on pH seems to be indirect (Abb. 2). Studies on the permeabilities of the egg shell and the embryonic membrane (\"vitelline membrane\"), the evidence of an oligosaccharide (Abb. 3) liberated from the \"spaltraum\" (Abb. 1) during egg-opening, and the determination of the osmotic pressure of the hatching process (50% hatching in 1.2--14. Osmols sucrose/1000 ml H2O; Abb. 4) led to the following hypothesis of hatching mechanism: After the activation of the granular gland of the miracidium an enzyme is released into the extra-embryonic \"spaltraum\". A polysaccharide is digested to an oligosaccharide which cannot permeate the egg shell and the embryonic membrane. The rising osmotic pressure bursts off the operculum."}
{"id": "PMID:3903", "title": "[Long-term treatment of chronic polyarthritis using benorylate].", "content": "The antiphlogistic and analgesic effect and the compatibility of benorylate, a acetamidophenyl-acetoxy-benzoate, was tested in 33 patients with rheumatoid arthritis in an open study over a period of 6 months. Benorylate is particularly qualified for treatment of a beginning rheumatoid arthritis and for diseases with a low inflammatory activity. For patients with high inflammatory activity treatment with this substance alone is not sufficient. Side effects are mainly subjective troubles. Severe side effects were not observed. Besides the usual laboratory investigations a regular control of the blood count is advisable during long term treatment. Like with other antirheumatic drugs occasional investigations of the stool for occult blood are recommended.", "contents": "[Long-term treatment of chronic polyarthritis using benorylate]. The antiphlogistic and analgesic effect and the compatibility of benorylate, a acetamidophenyl-acetoxy-benzoate, was tested in 33 patients with rheumatoid arthritis in an open study over a period of 6 months. Benorylate is particularly qualified for treatment of a beginning rheumatoid arthritis and for diseases with a low inflammatory activity. For patients with high inflammatory activity treatment with this substance alone is not sufficient. Side effects are mainly subjective troubles. Severe side effects were not observed. Besides the usual laboratory investigations a regular control of the blood count is advisable during long term treatment. Like with other antirheumatic drugs occasional investigations of the stool for occult blood are recommended."}
{"id": "PMID:3925", "title": "[Studies of Nocardia pellegrino SN 5108 pigment mutants: reasons for differences in pigmentation (author's transl)].", "content": "Yellow and white mutants of the strains Nocardia pellegrino SN 5108 R have been isolated. Regarding their morphological and physiological properties, the mutants are identical with the wild type bacteria with the exception of their pigmentation and lipid composition. However, the pigment composition (number, Rf-values and spectra of the pigment components) of the yellow mutant is identical with that of the wild type; as a consequence, the modified pigmentation of the yellow mutant cannot be explained by an altered pigment synthesis. The wild type cells and the mutant SN 5108 G contain three main pigment components designated as I, II and III. Components II and III posses a marked indicator character and show a bathochromic shift in solutions of pH 12 or higher. Components II and III contain functional groups which are able to react with acetic acid yielding acetylated products; after acetylating, no bathochromic shift in alkali occurs. Intact cells of the wild type retain their orange-red pigmentation in buffer solution with a pH-value of 12 or higher. Cells of the yellow mutant, however, change the yellow color immediately after the alkali treatment to orange-red; this new color is identical with that of the wild type and can be changed to yellow by placing the cells into 1 N HCl. Regarding these facts it seems to be very probable that the functional groups of the pigment components II and III are differently bound in the wild type and mutant cells. In the mutant, they are accessible to OH- ions yielding a bathochromic shift while in the wild type cells, OH- ions are unable to provoke this shift. It seems to be also probable that different lipids in the two strains are responsible for the binding of the pigments. So far known, this is the first observation about the occurence of pigment mutants with an altered pigment binding site in the cells.", "contents": "[Studies of Nocardia pellegrino SN 5108 pigment mutants: reasons for differences in pigmentation (author's transl)]. Yellow and white mutants of the strains Nocardia pellegrino SN 5108 R have been isolated. Regarding their morphological and physiological properties, the mutants are identical with the wild type bacteria with the exception of their pigmentation and lipid composition. However, the pigment composition (number, Rf-values and spectra of the pigment components) of the yellow mutant is identical with that of the wild type; as a consequence, the modified pigmentation of the yellow mutant cannot be explained by an altered pigment synthesis. The wild type cells and the mutant SN 5108 G contain three main pigment components designated as I, II and III. Components II and III posses a marked indicator character and show a bathochromic shift in solutions of pH 12 or higher. Components II and III contain functional groups which are able to react with acetic acid yielding acetylated products; after acetylating, no bathochromic shift in alkali occurs. Intact cells of the wild type retain their orange-red pigmentation in buffer solution with a pH-value of 12 or higher. Cells of the yellow mutant, however, change the yellow color immediately after the alkali treatment to orange-red; this new color is identical with that of the wild type and can be changed to yellow by placing the cells into 1 N HCl. Regarding these facts it seems to be very probable that the functional groups of the pigment components II and III are differently bound in the wild type and mutant cells. In the mutant, they are accessible to OH- ions yielding a bathochromic shift while in the wild type cells, OH- ions are unable to provoke this shift. It seems to be also probable that different lipids in the two strains are responsible for the binding of the pigments. So far known, this is the first observation about the occurence of pigment mutants with an altered pigment binding site in the cells."}
{"id": "PMID:3926", "title": "Formation and some factors influencing the activity of progesterone hydroxylases by Aspergillus niger.", "content": "The formation of progesterone hydroxylases by Aspergillus niger 173 was investigated. The constitution of the fermentation medium influenced both the yield and the type of enzymes catalyzing the transformation of progesterone. The enzyme yield also varied with the pH value at which induction was performed as well as with the buffer used. The transformation activity of progesterone was more pronounced with mycelia induced in citrate-phosphate than in phosphate buffer. The results demonstrated that induction of 6beta-hydroxylase was favoured at pH values near neutrality while that of 11alpha-hydroxylase in the presence of citrate ions. The transformation activity of progesterone was optimal at pH 5.0. The action of 11alpha-hydroxylase was also optimal at pH 5.0, but other hydroxylase showed pH optima between 2.2 and 4.0. Progesterone concentrations higher than 6 mg in 50 ml reaction mixture was a limiting factor for the rate of transformation activity.", "contents": "Formation and some factors influencing the activity of progesterone hydroxylases by Aspergillus niger. The formation of progesterone hydroxylases by Aspergillus niger 173 was investigated. The constitution of the fermentation medium influenced both the yield and the type of enzymes catalyzing the transformation of progesterone. The enzyme yield also varied with the pH value at which induction was performed as well as with the buffer used. The transformation activity of progesterone was more pronounced with mycelia induced in citrate-phosphate than in phosphate buffer. The results demonstrated that induction of 6beta-hydroxylase was favoured at pH values near neutrality while that of 11alpha-hydroxylase in the presence of citrate ions. The transformation activity of progesterone was optimal at pH 5.0. The action of 11alpha-hydroxylase was also optimal at pH 5.0, but other hydroxylase showed pH optima between 2.2 and 4.0. Progesterone concentrations higher than 6 mg in 50 ml reaction mixture was a limiting factor for the rate of transformation activity."}
{"id": "PMID:3927", "title": "[Preparation of the lectin B component from the hemagglutinin of Lens culinaris].", "content": "Out of a mixture of both lectins of the lentil (Lens culinaris) the component B may be separated rapidly and easily because of the different temperature sensitivity of haptene protected isolectins A and B.", "contents": "[Preparation of the lectin B component from the hemagglutinin of Lens culinaris]. Out of a mixture of both lectins of the lentil (Lens culinaris) the component B may be separated rapidly and easily because of the different temperature sensitivity of haptene protected isolectins A and B."}
{"id": "PMID:3940", "title": "Alanine formation and alanine aminotransferase activity in the nerve tissue with proliferating macroglia.", "content": "In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate saturation curves, apparent Km and pH optimum values in the tissue with proliferating macroglia and in the control did not differ from one another. The authors assume that a higher alanine aminotransferase activity in the tissue with macroglia proliferation can reflect either a higher synthesis of the enzyme in the altered tissue, or a predominance of glial elements in the altered tissue possessing a higher alanine aminotransferase activity than the nerve cells.", "contents": "Alanine formation and alanine aminotransferase activity in the nerve tissue with proliferating macroglia. In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate saturation curves, apparent Km and pH optimum values in the tissue with proliferating macroglia and in the control did not differ from one another. The authors assume that a higher alanine aminotransferase activity in the tissue with macroglia proliferation can reflect either a higher synthesis of the enzyme in the altered tissue, or a predominance of glial elements in the altered tissue possessing a higher alanine aminotransferase activity than the nerve cells."}
{"id": "PMID:3941", "title": "Influence of sugar content in soft bread on pH of human dental plaque.", "content": "Quantitative determination of monosaccharides, disaccharides and sorbitol by use of gas-liquid chromatography (GLC) was performed on thirty-three samples of different commercial soft bread. Maltose was found in all the bread samples. Fructose and glucose were found only in samples of sweetened bread. Sucrose was detected in 5 samples, lactose in 2, and sorbitol in 2. Up to 20 per cent of the fresh bread weight was found to be low-molecular weight carbohydrates. Plaque pH-changes were studied in 18 persons following a 30-second month rinse with each of 3 solutions: (1) 50% sucrose, (2) water extract of sweetened bread, and (3) water extract of unsweetened bread. Mouth rinsing with the extract of sweetened wheat bread (sucrose 7.7 per cent of the dough weight) caused pH-decreases in plaque which were significantly more pronounced than those induced by the water extract of unsweetened wheat bread.", "contents": "Influence of sugar content in soft bread on pH of human dental plaque. Quantitative determination of monosaccharides, disaccharides and sorbitol by use of gas-liquid chromatography (GLC) was performed on thirty-three samples of different commercial soft bread. Maltose was found in all the bread samples. Fructose and glucose were found only in samples of sweetened bread. Sucrose was detected in 5 samples, lactose in 2, and sorbitol in 2. Up to 20 per cent of the fresh bread weight was found to be low-molecular weight carbohydrates. Plaque pH-changes were studied in 18 persons following a 30-second month rinse with each of 3 solutions: (1) 50% sucrose, (2) water extract of sweetened bread, and (3) water extract of unsweetened bread. Mouth rinsing with the extract of sweetened wheat bread (sucrose 7.7 per cent of the dough weight) caused pH-decreases in plaque which were significantly more pronounced than those induced by the water extract of unsweetened wheat bread."}
{"id": "PMID:3939", "title": "Preliminary study of parenteral lorazepam in status epilepticus.", "content": "The authors report their experience with parenteral lorazepam in the acute treatment of 11 patients with EEG-confirmed status epilepticus. Ten adults and one 6-year-old child were injected respectively with 5 mg and 2.5 mg lorazepam. All of these patients exhibited prompt cessation of seizures both electrical and clinical. Some data indicate a longer lasting relief than that provided by an equal dose of diazepam.", "contents": "Preliminary study of parenteral lorazepam in status epilepticus. The authors report their experience with parenteral lorazepam in the acute treatment of 11 patients with EEG-confirmed status epilepticus. Ten adults and one 6-year-old child were injected respectively with 5 mg and 2.5 mg lorazepam. All of these patients exhibited prompt cessation of seizures both electrical and clinical. Some data indicate a longer lasting relief than that provided by an equal dose of diazepam."}
{"id": "PMID:3943", "title": "Structure-basicity and structure-affinity relationships of beta-adrenergic blocking agents.", "content": "pKa's of fourteen beta-receptor blockers, isoproterenol and norepinephrine, were determined potentiometrically. A Hammett analysis indicated that the influence of ring substituents on the basicity of the amines is attenuated by the ethanolic chain and abolished by the propranoloxy chain of beta-receptor blockers. The effect of ring substituents in phenoxypropranolamines upon affinity for the beta-adrengeric receptors is therefore unrelated to the strength of the bases. Two alterantive hypotheses are fowarded to explain why phenoxypropranolamines have greater affinities for the beta-receptors than phenethanolamines.", "contents": "Structure-basicity and structure-affinity relationships of beta-adrenergic blocking agents. pKa's of fourteen beta-receptor blockers, isoproterenol and norepinephrine, were determined potentiometrically. A Hammett analysis indicated that the influence of ring substituents on the basicity of the amines is attenuated by the ethanolic chain and abolished by the propranoloxy chain of beta-receptor blockers. The effect of ring substituents in phenoxypropranolamines upon affinity for the beta-adrengeric receptors is therefore unrelated to the strength of the bases. Two alterantive hypotheses are fowarded to explain why phenoxypropranolamines have greater affinities for the beta-receptors than phenethanolamines."}
{"id": "PMID:3944", "title": "Inhibition by acidosis of adenosine 3',5'-cyclic monophosphate accumulation and lipolysis in isolated rat fat cells.", "content": "Lipolysis and cyclic AMP accumulation were studied in isolated rat fat cells at normal (7.4) and decreased (7.0, 6.6) pH. Acidosis inhibited lipolysis and cyclic AMP accumulation due to NA non-competetively. Maximal lipolysis (3 muM NA) was inhibited by 25% at pH 7.0 and by 61% at pH 6.6 Cyclic AMP accumulation 5 min after 3 muM NA was inhibited by 57% at pH 7.0 and by 83% at pH 6.6. Between 10 and 60 minutes of incubation NA-stimulated lipolysis was linear at pH 7.4, whereas a progressively increasing inhibition was seen at lower pH. The FFA production was inhibited to the same degree as glycerol production by acidosis. The fraction of FFA associated with the cells was the same at all pHs. Thus, we have no evidence that acidosis inhibits lipolysis via accumulation of FFA intracellularly. NA-induced accumulation of 3H-cAMP from 3H-ATP, endogenously formed by prelabelling the cells with 3H-adenine, was inhibited by acidosis both in the presence and absence of theophylline in the incubation medium (by 48 and 44% respectively at pH 7.0 and by 74 and 68% at pH 6.6). Cyclic nucleotide phosphodiesterase in homogenates of fat cells was inhibited by decreasing the pH, whether measured at high or low substrate concentrations. Basal adenylyl cyclase activity in a cell membrane fraction from fat cells was affected to a minor degree, while NA-stimulated activity was inhibited by decreased pH. The response to 3 muM NA at pH 6.6 was inhibited by 43% relative to control. The results show that acidosis inhibits NA-induced cyclic AMP accumulation by interfering with the formation, rather than the inactivation of the nucleotide. Since NA-induced lipolysis is a cyclic AMP-mediated process it is suggested that at least part of the antilipolytic effect of acidosis is due to inhibition of cyclic AMP formation.", "contents": "Inhibition by acidosis of adenosine 3',5'-cyclic monophosphate accumulation and lipolysis in isolated rat fat cells. Lipolysis and cyclic AMP accumulation were studied in isolated rat fat cells at normal (7.4) and decreased (7.0, 6.6) pH. Acidosis inhibited lipolysis and cyclic AMP accumulation due to NA non-competetively. Maximal lipolysis (3 muM NA) was inhibited by 25% at pH 7.0 and by 61% at pH 6.6 Cyclic AMP accumulation 5 min after 3 muM NA was inhibited by 57% at pH 7.0 and by 83% at pH 6.6. Between 10 and 60 minutes of incubation NA-stimulated lipolysis was linear at pH 7.4, whereas a progressively increasing inhibition was seen at lower pH. The FFA production was inhibited to the same degree as glycerol production by acidosis. The fraction of FFA associated with the cells was the same at all pHs. Thus, we have no evidence that acidosis inhibits lipolysis via accumulation of FFA intracellularly. NA-induced accumulation of 3H-cAMP from 3H-ATP, endogenously formed by prelabelling the cells with 3H-adenine, was inhibited by acidosis both in the presence and absence of theophylline in the incubation medium (by 48 and 44% respectively at pH 7.0 and by 74 and 68% at pH 6.6). Cyclic nucleotide phosphodiesterase in homogenates of fat cells was inhibited by decreasing the pH, whether measured at high or low substrate concentrations. Basal adenylyl cyclase activity in a cell membrane fraction from fat cells was affected to a minor degree, while NA-stimulated activity was inhibited by decreased pH. The response to 3 muM NA at pH 6.6 was inhibited by 43% relative to control. The results show that acidosis inhibits NA-induced cyclic AMP accumulation by interfering with the formation, rather than the inactivation of the nucleotide. Since NA-induced lipolysis is a cyclic AMP-mediated process it is suggested that at least part of the antilipolytic effect of acidosis is due to inhibition of cyclic AMP formation."}
{"id": "PMID:3945", "title": "Cyclic AMP-dependent and independent inhibition of lipolysis by adenosine and decreased pH.", "content": "NA-stimulated lipolysis and cAMP formation in isolated rat fat cells is inhibited by acidosis. In the present report we have examined the quantitative relationship between lipolysis and cAMP formation at normal and reduced pH and the possible involvement of adenosine, an endogenous inhibitor of cAMP formation. Adenosine antagonized cAMP accumulation and to a considerably lower degree lipolysis, effects potentiated by acidosis. Theophylline, an antagonist of adenosine effects, stimulated lipolysis and cAMP-accumulation, and potentiated responses to NA. Adenosine deaminase (ADA) had theophylline-like effects. Acidosis inhibited lipolysis and cAMP accumulation induced by ADA and theophylline to a larger extent than those induced by NA. It is suggested that adenosine modulates fat cell cAMP production and may contribute to the antilipolytic effect of acidosis. There was a curvilinear relationship between cAMP elevation and glycerol production in fat cell suspensions, which was different at pH 7.4 and at pH 6.6. The amount of cAMP needed for half-maximal activation of lipolysis increased from 1.3 (pH 7.4) to 3.1 pMol X 10(-5) cells (pH 6.6). The maximal glycerol production was reduced from 1 300 to 900 nMol X 10(-5) cells. The antilipolytic effect of acidosis is apparently due partly to an inhibition of cAMP formation and partly to inhibition of subsequent step(s) in the activation sequence.", "contents": "Cyclic AMP-dependent and independent inhibition of lipolysis by adenosine and decreased pH. NA-stimulated lipolysis and cAMP formation in isolated rat fat cells is inhibited by acidosis. In the present report we have examined the quantitative relationship between lipolysis and cAMP formation at normal and reduced pH and the possible involvement of adenosine, an endogenous inhibitor of cAMP formation. Adenosine antagonized cAMP accumulation and to a considerably lower degree lipolysis, effects potentiated by acidosis. Theophylline, an antagonist of adenosine effects, stimulated lipolysis and cAMP-accumulation, and potentiated responses to NA. Adenosine deaminase (ADA) had theophylline-like effects. Acidosis inhibited lipolysis and cAMP accumulation induced by ADA and theophylline to a larger extent than those induced by NA. It is suggested that adenosine modulates fat cell cAMP production and may contribute to the antilipolytic effect of acidosis. There was a curvilinear relationship between cAMP elevation and glycerol production in fat cell suspensions, which was different at pH 7.4 and at pH 6.6. The amount of cAMP needed for half-maximal activation of lipolysis increased from 1.3 (pH 7.4) to 3.1 pMol X 10(-5) cells (pH 6.6). The maximal glycerol production was reduced from 1 300 to 900 nMol X 10(-5) cells. The antilipolytic effect of acidosis is apparently due partly to an inhibition of cAMP formation and partly to inhibition of subsequent step(s) in the activation sequence."}
{"id": "PMID:3946", "title": "Modification of the gastric secretory response to sham feeding by acidification of the antrum and the duodenum in dogs.", "content": "The effect of closure of a gastric cannula on the acid response to sham feeding was studied in Pavlov-pouch dogs with intact antro-duodenal regions as well as in antrectomized dogs with gastroduodenostomies. In the latter dogs, the sham feeding response was augmented by infusions of low doses of exogenous gastrin. The acid output after sham feeding in intact dogs was reduced on average by 59% by closure of the gastric cannula. In antrectomized dogs receiving a back-ground stimulation with gastrin, the response to ham feeding was not inhibited by closure of the cannula. The results suggest that the observed hypersecretory response to sham feeding after diversion of gastric acid from antrum and duodenum is mainly due to inactivation of antral inhibitory mechanisms. The pepsin secretion following sham feeding was not consistently changed by closure of the gastric cannula.", "contents": "Modification of the gastric secretory response to sham feeding by acidification of the antrum and the duodenum in dogs. The effect of closure of a gastric cannula on the acid response to sham feeding was studied in Pavlov-pouch dogs with intact antro-duodenal regions as well as in antrectomized dogs with gastroduodenostomies. In the latter dogs, the sham feeding response was augmented by infusions of low doses of exogenous gastrin. The acid output after sham feeding in intact dogs was reduced on average by 59% by closure of the gastric cannula. In antrectomized dogs receiving a back-ground stimulation with gastrin, the response to ham feeding was not inhibited by closure of the cannula. The results suggest that the observed hypersecretory response to sham feeding after diversion of gastric acid from antrum and duodenum is mainly due to inactivation of antral inhibitory mechanisms. The pepsin secretion following sham feeding was not consistently changed by closure of the gastric cannula."}
{"id": "PMID:3947", "title": "Beta adrenergic dilator component of the sympathetic vascular response in skeletal muscle. Influence on the micro-circulation and on transcapillary exchange.", "content": "A neurogenic beta-adrenergic vasodilatation in skeletal muscle has been indicated by some recent investigations. The present study describes the extent to which this neurogenic beta-dilator mechanism contributes to the integrated vascular response in consecutive sections of the muscle vascular bed during sympathetic nerve activation. This was done by studying the vascular reactions to graded sympathetic stimulation (1-16 Hz) before and after beta-adrenoceptor blockade. Beta-blockade did not influence significantly the sympathetically induced changes of total muscle vascular resistance or capacitance. Vascular tone in the \"micro-vessels\" during stimulation was, however, clearly more pronounced in the beta-blocked than in the non-blocked region, as revealed by segmental resistance analysis and by determination of precapillary sphincter tone (CFC). In addition, beta-blockade markedly reduced the net transcapillary absorption of extravascular fluid evoked by nerve activation. This effect could be ascribed to the mentioned influence on the precapillary sphincters, leading to a decrease of the number of capillaries available for transcapillary exchange, and to a limitation of the nerve induced fall of capillary hydrostatic pressure. The described effects of alpha-blockade were observed at all rates of sympathetic stimulation.--The conclusion was reached that the beta-adrenergic dilator component of the sympathetic vascular response in skeletal muscle significantly modifies the alpha-adrenergic constriction in the micro-vessels. It is suggested that, in the intact organism, this neurogenic beta-dilator mechanism is primarily aimed at improving the transcapillary exchange.", "contents": "Beta adrenergic dilator component of the sympathetic vascular response in skeletal muscle. Influence on the micro-circulation and on transcapillary exchange. A neurogenic beta-adrenergic vasodilatation in skeletal muscle has been indicated by some recent investigations. The present study describes the extent to which this neurogenic beta-dilator mechanism contributes to the integrated vascular response in consecutive sections of the muscle vascular bed during sympathetic nerve activation. This was done by studying the vascular reactions to graded sympathetic stimulation (1-16 Hz) before and after beta-adrenoceptor blockade. Beta-blockade did not influence significantly the sympathetically induced changes of total muscle vascular resistance or capacitance. Vascular tone in the \"micro-vessels\" during stimulation was, however, clearly more pronounced in the beta-blocked than in the non-blocked region, as revealed by segmental resistance analysis and by determination of precapillary sphincter tone (CFC). In addition, beta-blockade markedly reduced the net transcapillary absorption of extravascular fluid evoked by nerve activation. This effect could be ascribed to the mentioned influence on the precapillary sphincters, leading to a decrease of the number of capillaries available for transcapillary exchange, and to a limitation of the nerve induced fall of capillary hydrostatic pressure. The described effects of alpha-blockade were observed at all rates of sympathetic stimulation.--The conclusion was reached that the beta-adrenergic dilator component of the sympathetic vascular response in skeletal muscle significantly modifies the alpha-adrenergic constriction in the micro-vessels. It is suggested that, in the intact organism, this neurogenic beta-dilator mechanism is primarily aimed at improving the transcapillary exchange."}
{"id": "PMID:3948", "title": "Haematologic adaptation in patients with chronic bronchitis and pulmonary insufficiency.", "content": "The relationship between respiratory insufficiency, expressed by gas tensions in blood and bone marrow, and haematologic adaptation has been studied in 82 men with chronic bronchitis and persistent breathlessness for at least one year. For the group as a whole and for various subgroups, a linear correlation was demonstrated between arterial hypoxia and Hb concentration, haematocrit, blood volume, Hb mass and erythrocyte volume, respectively. The increase in Hb concentration compensated for the fall in arterial oxygen saturation. Only for one subgroup, with a pH difference between arterial and venous blood larger than or equal to 0.08, was no correlation found between the degree of hypoxia and Hb concentration. The haematologic parameters correlated significantly better with arterial oxygen tensions than with oxygen tensions in the bone marrow. There was no indication that decreased oxygen supply to the bone marrow led to the increased erythrocyte and Hb production in patients with arterial hypoxia caused by chronic bronchitis.", "contents": "Haematologic adaptation in patients with chronic bronchitis and pulmonary insufficiency. The relationship between respiratory insufficiency, expressed by gas tensions in blood and bone marrow, and haematologic adaptation has been studied in 82 men with chronic bronchitis and persistent breathlessness for at least one year. For the group as a whole and for various subgroups, a linear correlation was demonstrated between arterial hypoxia and Hb concentration, haematocrit, blood volume, Hb mass and erythrocyte volume, respectively. The increase in Hb concentration compensated for the fall in arterial oxygen saturation. Only for one subgroup, with a pH difference between arterial and venous blood larger than or equal to 0.08, was no correlation found between the degree of hypoxia and Hb concentration. The haematologic parameters correlated significantly better with arterial oxygen tensions than with oxygen tensions in the bone marrow. There was no indication that decreased oxygen supply to the bone marrow led to the increased erythrocyte and Hb production in patients with arterial hypoxia caused by chronic bronchitis."}
{"id": "PMID:3949", "title": "Pattern of enzyme activity following acute myocardial infarction with special reference to gamma-glutamyl transpeptidase.", "content": "The present study on 55 consecutive patients with acute myocardial infarction (AMI) draws attention to the relationship between different enzyme maxima in AMI, with special reference to serum gamma-glutamyl transpeptidase (S-GT). In more than 60% of the patients the S-GT was increased during the hospital stay. The S-GT rise nearly always began during the first days,  reached a maximum within 5--8 days and normalized with 2--3 weeks. We failed to find the late increase in S-GT reported by others. The rise of S-GT is particularly common in patients with inferior infarction, with or without right ventricular involvement. We conclude that S-GT activity is not a useful early or late indicator of AMI but a very sensitive test for hepatic dysfunction in patients with AMI.", "contents": "Pattern of enzyme activity following acute myocardial infarction with special reference to gamma-glutamyl transpeptidase. The present study on 55 consecutive patients with acute myocardial infarction (AMI) draws attention to the relationship between different enzyme maxima in AMI, with special reference to serum gamma-glutamyl transpeptidase (S-GT). In more than 60% of the patients the S-GT was increased during the hospital stay. The S-GT rise nearly always began during the first days,  reached a maximum within 5--8 days and normalized with 2--3 weeks. We failed to find the late increase in S-GT reported by others. The rise of S-GT is particularly common in patients with inferior infarction, with or without right ventricular involvement. We conclude that S-GT activity is not a useful early or late indicator of AMI but a very sensitive test for hepatic dysfunction in patients with AMI."}
{"id": "PMID:3954", "title": "Diamine oxydase in rabbit small intestine: separations from a soluble monoamine oxidase, properties and pathophysiological significance in intestinal ischemia.", "content": "From all mammals investigated so far only in rabbits diamine oxidase could not be detected in any tissue except the gut. Thus this species was chosen for studying the physiological and pathophysiological function of this enzyme in the gastrointestinal tract. By gel filtration on Sephadex G 50 and G 200 the enzyme was purified 100-fold, separated from a soluble monoamine oxidase, and the properties of the two enzymes were determined. Diamine oxidase from rabbit small intestine deaminated putrecine (Km = 1.3 times 10(-4) M, pH-optimum 6.4-6.9) and histamine (Km = 8 times 10(-5) M, pH-optimum 7.5), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. Soluble monoamine oxidase from rabbit small intestine catabolized serotonin (Km = 1.8 times 10(-4) M, pH-optimum 8.8) but not putrescine and histamine, and was inhibited by pargyline, but not by aminoguanidine. Based on its properties in vitro intestinal diamine oxidase could inactivate the vasoactive biogenic amine histamine in vivo. To confirm this hypothesis, in rabbits the small intestine was damaged severely by inducing total intestinal ischemia, which occurs as mesenteric infarction also in human subjects and is accompanied by histamine release. Treatment with aminoguanidine and ischemia killed the animals 3-times faster than ischemia alone, which supported our hypothesis on a protective role of intestinal diamine oxidase against histamine.", "contents": "Diamine oxydase in rabbit small intestine: separations from a soluble monoamine oxidase, properties and pathophysiological significance in intestinal ischemia. From all mammals investigated so far only in rabbits diamine oxidase could not be detected in any tissue except the gut. Thus this species was chosen for studying the physiological and pathophysiological function of this enzyme in the gastrointestinal tract. By gel filtration on Sephadex G 50 and G 200 the enzyme was purified 100-fold, separated from a soluble monoamine oxidase, and the properties of the two enzymes were determined. Diamine oxidase from rabbit small intestine deaminated putrecine (Km = 1.3 times 10(-4) M, pH-optimum 6.4-6.9) and histamine (Km = 8 times 10(-5) M, pH-optimum 7.5), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. Soluble monoamine oxidase from rabbit small intestine catabolized serotonin (Km = 1.8 times 10(-4) M, pH-optimum 8.8) but not putrescine and histamine, and was inhibited by pargyline, but not by aminoguanidine. Based on its properties in vitro intestinal diamine oxidase could inactivate the vasoactive biogenic amine histamine in vivo. To confirm this hypothesis, in rabbits the small intestine was damaged severely by inducing total intestinal ischemia, which occurs as mesenteric infarction also in human subjects and is accompanied by histamine release. Treatment with aminoguanidine and ischemia killed the animals 3-times faster than ischemia alone, which supported our hypothesis on a protective role of intestinal diamine oxidase against histamine."}
{"id": "PMID:3959", "title": "Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition.", "content": "Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.", "contents": "Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition. Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein."}
{"id": "PMID:3960", "title": "Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction.", "content": "With use of a canine model of occlusion of the left anterior descending coronary artery and an intracellular lactic dehydrogenase stain to measure infarct size directly, the effects of allopurinol, methylprednisolone sodium succinate and propranolol were studied. Allopurinol did not influence the extent of myocardial necrosis, whereas both methylprednisolone and propranolol significantly reduced myocardial infarct size. Possible mechanisms of action and clinical applicability of these agents are discussed.", "contents": "Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction. With use of a canine model of occlusion of the left anterior descending coronary artery and an intracellular lactic dehydrogenase stain to measure infarct size directly, the effects of allopurinol, methylprednisolone sodium succinate and propranolol were studied. Allopurinol did not influence the extent of myocardial necrosis, whereas both methylprednisolone and propranolol significantly reduced myocardial infarct size. Possible mechanisms of action and clinical applicability of these agents are discussed."}
{"id": "PMID:3961", "title": "Effects of cedilanid-D in combination with metoprolol on exercise tolerance and systolic time intervals in angina pectoris.", "content": "The interaction between cedilanid-D and metoprolol, a selective beta receptor blocking agent, on exercise tolerance and systolic intervals was studied in 15 patients with angina pectoris. The patients had been treated with metoprolol for several months in a dose of 50 mg, three times daily (one patient received 25 mg three times daily). Each patient participated in two studies separated by at least 1 week. After arriving at the laboratory each received 50 mg of metoprolol orally; thereafter, either cedilanid-D or placebo was infused intravenously in a double-blind study performed in randomized order. When the effect of the drugs was maximal, the systolic intervals and the heart volume were recorded at rest, and the exercise tolerance was tested with a bicycle ergometer. The mean maximal value of plasma concentrations of metoprolol assessed during the study was about 50 ng/ml but the variation among subjects was great (20 to 187 ng/ml). After administration of cedilanid-D there was a shortening of the pre-ejection period and left ventricular ejection time compared with results after placebo; the reduction was similar to that found after administration  of cedilanid-D without beta blocking drugs. The total heart volume decreased by an average of 55 ml, but the individual variation was great. The patients' average work capacity, expressed as total work, was not altered by cedilanid-D when compared with results after placebo. No relation was found between initial heart size and the effect of cedilanid-D on capacity for physical work. It therefore appears that there is no indication for the routine use of digitalis during beta blocking therapy in patients with angina pectoris who do not have cardiac failure.", "contents": "Effects of cedilanid-D in combination with metoprolol on exercise tolerance and systolic time intervals in angina pectoris. The interaction between cedilanid-D and metoprolol, a selective beta receptor blocking agent, on exercise tolerance and systolic intervals was studied in 15 patients with angina pectoris. The patients had been treated with metoprolol for several months in a dose of 50 mg, three times daily (one patient received 25 mg three times daily). Each patient participated in two studies separated by at least 1 week. After arriving at the laboratory each received 50 mg of metoprolol orally; thereafter, either cedilanid-D or placebo was infused intravenously in a double-blind study performed in randomized order. When the effect of the drugs was maximal, the systolic intervals and the heart volume were recorded at rest, and the exercise tolerance was tested with a bicycle ergometer. The mean maximal value of plasma concentrations of metoprolol assessed during the study was about 50 ng/ml but the variation among subjects was great (20 to 187 ng/ml). After administration of cedilanid-D there was a shortening of the pre-ejection period and left ventricular ejection time compared with results after placebo; the reduction was similar to that found after administration  of cedilanid-D without beta blocking drugs. The total heart volume decreased by an average of 55 ml, but the individual variation was great. The patients' average work capacity, expressed as total work, was not altered by cedilanid-D when compared with results after placebo. No relation was found between initial heart size and the effect of cedilanid-D on capacity for physical work. It therefore appears that there is no indication for the routine use of digitalis during beta blocking therapy in patients with angina pectoris who do not have cardiac failure."}
{"id": "PMID:3963", "title": "Beta adrenergic blockade and diuretic therapy in benign essential hypertension: A dynamic assessment.", "content": "Beta adrenergic receptor antagonists (beta blockers) differ greatly in their cardioselectivity and intrinsic sympathomimetic activity, and these differences may have important therapeutic consequences. We have therefore studied the effect on blood pressure, heart rate and plasma renin activity of the beta blocking drug oxprenolol (Trasicor) which has considerable intrinsic sympathomimetic activity, both alone and in combination with the benzothiadiazine cyclopenthiazide. Eleven patients with mild to moderate benign essential hypertension were randomly allocated to one of two treatment groups. Oxprenolol was given as the first drug to Group 1, and cyclopenthiazide as the first drug to Group 2. The patients were assessed before the start of treatment, after 2 to 3 weeks of treatment with one drug and after a further 2 to 3 weeks of treatment with both drugs. Heart rate, blood pressure and plasma renin activity were measured with the patients recumbent and after a standardized tilt to 85 degrees to provide a reflection of day to day cardiovascular stress. Oxprenolol reduced arterial blood pressure without inducing significant bradycardia. The addition of cyclopenthiazide had little further effect. Oxprenolol alone suppressed plasma renin activity both at rest and during tilt and also abolished the increase in plasma renin activity after administration of cyclopenthiazide. The combination of (1) moderate reduction of blood pressure. (2) inhibition of the otherwise inevitable increase in plasma renin activity with the use of a diuretic drug, and (3) only moderate inhibition of overall sympathetic activity indicates that it is possible to achieve physiologic balance with the appropriate beta blocking drug.", "contents": "Beta adrenergic blockade and diuretic therapy in benign essential hypertension: A dynamic assessment. Beta adrenergic receptor antagonists (beta blockers) differ greatly in their cardioselectivity and intrinsic sympathomimetic activity, and these differences may have important therapeutic consequences. We have therefore studied the effect on blood pressure, heart rate and plasma renin activity of the beta blocking drug oxprenolol (Trasicor) which has considerable intrinsic sympathomimetic activity, both alone and in combination with the benzothiadiazine cyclopenthiazide. Eleven patients with mild to moderate benign essential hypertension were randomly allocated to one of two treatment groups. Oxprenolol was given as the first drug to Group 1, and cyclopenthiazide as the first drug to Group 2. The patients were assessed before the start of treatment, after 2 to 3 weeks of treatment with one drug and after a further 2 to 3 weeks of treatment with both drugs. Heart rate, blood pressure and plasma renin activity were measured with the patients recumbent and after a standardized tilt to 85 degrees to provide a reflection of day to day cardiovascular stress. Oxprenolol reduced arterial blood pressure without inducing significant bradycardia. The addition of cyclopenthiazide had little further effect. Oxprenolol alone suppressed plasma renin activity both at rest and during tilt and also abolished the increase in plasma renin activity after administration of cyclopenthiazide. The combination of (1) moderate reduction of blood pressure. (2) inhibition of the otherwise inevitable increase in plasma renin activity with the use of a diuretic drug, and (3) only moderate inhibition of overall sympathetic activity indicates that it is possible to achieve physiologic balance with the appropriate beta blocking drug."}
{"id": "PMID:3964", "title": "Control of renin release: a review of experimental evidence and clinical implications.", "content": "Present knowledge of the mechanisms regulating release of renin is reviewed with particular emphasis on neural factors. Evidence is given for a direct effect of renal innervation on beta adrenergic receptors in juxtaglomerular cells, and for the involvement of reflex release of renin in conditions such as tilting and acute salt depletion. Participation of neural and nonneural mechanisms of control is also shown to occur in other conditions, such as aortic constriction and hemorrhage. The view is held that neural sympathetic factors might explain some of the renin disturbances found in essential hypertension. First, in patients with high renin hypertension part of the hypertension is renin-dependent, and these pressor levels of renin seem to be neurally induced since they can commonly be suppressed by beta adrenoreceptor blocking agents. Second, the hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release. Therefore a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension and as a better guide to therapeutic management. Indeed, most of the available antihypertensive drugs act on sympathetic activity, body fluid volume or renin, and this multifaceted profile would provide more rational guidelines for treatment.", "contents": "Control of renin release: a review of experimental evidence and clinical implications. Present knowledge of the mechanisms regulating release of renin is reviewed with particular emphasis on neural factors. Evidence is given for a direct effect of renal innervation on beta adrenergic receptors in juxtaglomerular cells, and for the involvement of reflex release of renin in conditions such as tilting and acute salt depletion. Participation of neural and nonneural mechanisms of control is also shown to occur in other conditions, such as aortic constriction and hemorrhage. The view is held that neural sympathetic factors might explain some of the renin disturbances found in essential hypertension. First, in patients with high renin hypertension part of the hypertension is renin-dependent, and these pressor levels of renin seem to be neurally induced since they can commonly be suppressed by beta adrenoreceptor blocking agents. Second, the hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release. Therefore a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension and as a better guide to therapeutic management. Indeed, most of the available antihypertensive drugs act on sympathetic activity, body fluid volume or renin, and this multifaceted profile would provide more rational guidelines for treatment."}
{"id": "PMID:3965", "title": "Syncope with prolonged QT interval.", "content": "Four children with syncope had a prolonged QT interval on the electrocardiogram. Neurologic studies were negative. One patient had associated deaf mutism, one had a family history of sudden death and prolonged QT interval, and two had ventricular arrhythmias while being monitored in the hospital. Treatment with propranolol hydrochloride eliminated the syncope in all patients, although the ECGs remained abnormal.", "contents": "Syncope with prolonged QT interval. Four children with syncope had a prolonged QT interval on the electrocardiogram. Neurologic studies were negative. One patient had associated deaf mutism, one had a family history of sudden death and prolonged QT interval, and two had ventricular arrhythmias while being monitored in the hospital. Treatment with propranolol hydrochloride eliminated the syncope in all patients, although the ECGs remained abnormal."}
{"id": "PMID:3967", "title": "Quantitative determination of piperazine citrate in piperazine citrate syrup USP.", "content": "An assay for piperazine citrate in Piperazine Citrate Syrup USP is described. The assay method is based on the formation of a complex of piperazine with an acid dye, bromothymol blue. The complex can be extracted with chloroform and measured spectrophotometrically. The method is accurate and requires only 15 minutes for analysis, compared to four to five hours by the USP method.", "contents": "Quantitative determination of piperazine citrate in piperazine citrate syrup USP. An assay for piperazine citrate in Piperazine Citrate Syrup USP is described. The assay method is based on the formation of a complex of piperazine with an acid dye, bromothymol blue. The complex can be extracted with chloroform and measured spectrophotometrically. The method is accurate and requires only 15 minutes for analysis, compared to four to five hours by the USP method."}
{"id": "PMID:3968", "title": "Personality and job satisfaction of medical technologists.", "content": "The personality characteristics and job satisfaction patterns of a volunteer group of practicing medical technologists were measured by the Myers-Briggs Type Indicator and the Job Description Index. Data analysis was based on three groups of female subjects: clinical practitioners, educators, and administrators. There was little primary impact of personality upon job satisfaction, although definite patterns of personality are identifiable in the three groups. Implications for counseling students and placing practitioners in satisfying jobs were suggested, and additional studies to be conducted were identified.", "contents": "Personality and job satisfaction of medical technologists. The personality characteristics and job satisfaction patterns of a volunteer group of practicing medical technologists were measured by the Myers-Briggs Type Indicator and the Job Description Index. Data analysis was based on three groups of female subjects: clinical practitioners, educators, and administrators. There was little primary impact of personality upon job satisfaction, although definite patterns of personality are identifiable in the three groups. Implications for counseling students and placing practitioners in satisfying jobs were suggested, and additional studies to be conducted were identified."}
{"id": "PMID:3971", "title": "Ventilatory and blood gas changes during laparoscopy with local anesthesia.", "content": "A study was performed on a series of healthy patients undergoing laparoscopy for tubal ligation with local anesthesia in a non-operating room setting. Ventilatory parameters, blood gas, pH, blood pressure, and pulse were monitored. The results revealed that no adverse effect on hemoglobin saturation or carbon dioxide exchange were found when fentanyl alone was used as a supplementary analgesic. An occasional vagal reflex was observed, and it is recommended that an intravenous line be established in the event that pharmacologic intervention should become necessary. Nitrous oxide produced les with this minimal analgesia.", "contents": "Ventilatory and blood gas changes during laparoscopy with local anesthesia. A study was performed on a series of healthy patients undergoing laparoscopy for tubal ligation with local anesthesia in a non-operating room setting. Ventilatory parameters, blood gas, pH, blood pressure, and pulse were monitored. The results revealed that no adverse effect on hemoglobin saturation or carbon dioxide exchange were found when fentanyl alone was used as a supplementary analgesic. An occasional vagal reflex was observed, and it is recommended that an intravenous line be established in the event that pharmacologic intervention should become necessary. Nitrous oxide produced les with this minimal analgesia."}
{"id": "PMID:3969", "title": "Bactericidal activity and pharmacology of flucloxacillin.", "content": "Flucloxacillin, a recent addition to the group of isoxazolyl penicillins, was studied in vitro and in normal volunteers. The bactericidal activity of the drug against most strains of gram-positive bacteria including penicillin-resistant Staphylococcus aureus was similar to that of oxacillin and approximately fourfold greater than that of cloxacillin. Each of the three penicillins was administered orally to a group of ten volunteers for eight days in a dose of 500 mg four times a day. The mean concentrations of flucloxacillin in the serum were two- to sixfold higher than those of the other two agents on the first, fourth and eighth days of therapy. The percentage of flucloxacillin bound by serum protein was 94.6 per cent; for cloxacillin and oxacillin the values were 93.5 and 91.5 per cent, respectively. Using these data, the concentrations of free flucloxacillin in serum were found to be twice as high as those of cloxacillin and oxacillin. These findings suggest that, when administered orally, this new agent may offer some therapeutic advantage over oxacillin and cloxacillin.", "contents": "Bactericidal activity and pharmacology of flucloxacillin. Flucloxacillin, a recent addition to the group of isoxazolyl penicillins, was studied in vitro and in normal volunteers. The bactericidal activity of the drug against most strains of gram-positive bacteria including penicillin-resistant Staphylococcus aureus was similar to that of oxacillin and approximately fourfold greater than that of cloxacillin. Each of the three penicillins was administered orally to a group of ten volunteers for eight days in a dose of 500 mg four times a day. The mean concentrations of flucloxacillin in the serum were two- to sixfold higher than those of the other two agents on the first, fourth and eighth days of therapy. The percentage of flucloxacillin bound by serum protein was 94.6 per cent; for cloxacillin and oxacillin the values were 93.5 and 91.5 per cent, respectively. Using these data, the concentrations of free flucloxacillin in serum were found to be twice as high as those of cloxacillin and oxacillin. These findings suggest that, when administered orally, this new agent may offer some therapeutic advantage over oxacillin and cloxacillin."}
{"id": "PMID:3970", "title": "Nephrology rounds, University of Iowa Hospitals: renal tubular acidosis.", "content": "We have discussed two patients who had renal tubular acidosis complicated by hypokalemia. The first patient had a distal acidifying defect. Circumstantial evidence has been presented suggesting that exposure to toluene-diisocyanate or toluene-diamine played a role in the pathogenesis. The acidosis and the hypokalemia of this patient were easily corrected by the administration of small amounts of sodium bicarbonate without potassium supplementation. The second patient had an interstitial nephritis of unknown etiology and presented with moderate renal insufficiency, renal tubular acidosis, and proximal as well as distal acidifying defects. The proximal tubular dysfunction was associated with general aminoaciduria and glucosuria. This patient required large quantities of both alkali and potassium to correct the electrolyte abnormalities. The mechanisms of potassium wasting in proximal and distal renal tubular acidosis are reviewed. A classification is presented of cellular defects that may underlie the different renal acidifying defects. Attempts to distinguish between pump and permeability defects from urinary pCO2 levels must take into account the simultaneous HCO-3 concentration, since large pCO2 elevations require the presence of ample HCO-3 in the urine. Permeability defects may impair urinary acidification by either abnormal back flux of H+ out of the lumen or increased influx of HCO-3 into the lumen. In studies of acidification in vitro, amphotericin B causes increased H+ permeability and has little effect on HCO-3 permeability. Toluene-diamine causes a marked permeability defect which is reversible, but remains to be defined in terms of the ion species, HCO-3 or H+, affected. At times, hyperchloremic acidosis is caused by distal defects in net acid excretion that occur without impairment of the H+ gradient. In certain patients with hypoaldosteronism, for example, distal H+ secretion may be reduced without change in the force of the H+ pump.", "contents": "Nephrology rounds, University of Iowa Hospitals: renal tubular acidosis. We have discussed two patients who had renal tubular acidosis complicated by hypokalemia. The first patient had a distal acidifying defect. Circumstantial evidence has been presented suggesting that exposure to toluene-diisocyanate or toluene-diamine played a role in the pathogenesis. The acidosis and the hypokalemia of this patient were easily corrected by the administration of small amounts of sodium bicarbonate without potassium supplementation. The second patient had an interstitial nephritis of unknown etiology and presented with moderate renal insufficiency, renal tubular acidosis, and proximal as well as distal acidifying defects. The proximal tubular dysfunction was associated with general aminoaciduria and glucosuria. This patient required large quantities of both alkali and potassium to correct the electrolyte abnormalities. The mechanisms of potassium wasting in proximal and distal renal tubular acidosis are reviewed. A classification is presented of cellular defects that may underlie the different renal acidifying defects. Attempts to distinguish between pump and permeability defects from urinary pCO2 levels must take into account the simultaneous HCO-3 concentration, since large pCO2 elevations require the presence of ample HCO-3 in the urine. Permeability defects may impair urinary acidification by either abnormal back flux of H+ out of the lumen or increased influx of HCO-3 into the lumen. In studies of acidification in vitro, amphotericin B causes increased H+ permeability and has little effect on HCO-3 permeability. Toluene-diamine causes a marked permeability defect which is reversible, but remains to be defined in terms of the ion species, HCO-3 or H+, affected. At times, hyperchloremic acidosis is caused by distal defects in net acid excretion that occur without impairment of the H+ gradient. In certain patients with hypoaldosteronism, for example, distal H+ secretion may be reduced without change in the force of the H+ pump."}
{"id": "PMID:3973", "title": "Effects of salicylate and bile salt on ion transport by isolated gastric mucosa of the rabbit.", "content": "The effects of luminal addition of salicylate and taurocholate on ion transport by fundic mucosa were examined in vitro using isotopic and pH stat techniques. Salicylate, 3 mM, did not alter, but 20 mM caused a 40% decrease in, the acid secretory rate. Taurocholate, 20 mM, caused a transient, apparent cessation of acid secretion followed by stimulation. Salicylate, 3 or 20 mM, increased Na+ but not Cl- permeability at luminal pH 7. At luminal pH 4, however, salicylate increased Cl- in addition to Na+ and H+ permeability. Taurocholate, 10 or 20 mM, increased both cation and anion permeability at pH 7 and 4. Addition of salicylate or taurocholate results in stimulation of net Na+ transport. While salicylate and taurocholate increase cation permeability at pH 7, they have differing effects on acid secretion and anion permeability. The data suggest that salicylate and taurocholate alter cation permeability by different mechanisms and are consistent with the concept that enhanced diffusion of H+ into the tissue causes a nonspecific alteration in the permeability pathway.", "contents": "Effects of salicylate and bile salt on ion transport by isolated gastric mucosa of the rabbit. The effects of luminal addition of salicylate and taurocholate on ion transport by fundic mucosa were examined in vitro using isotopic and pH stat techniques. Salicylate, 3 mM, did not alter, but 20 mM caused a 40% decrease in, the acid secretory rate. Taurocholate, 20 mM, caused a transient, apparent cessation of acid secretion followed by stimulation. Salicylate, 3 or 20 mM, increased Na+ but not Cl- permeability at luminal pH 7. At luminal pH 4, however, salicylate increased Cl- in addition to Na+ and H+ permeability. Taurocholate, 10 or 20 mM, increased both cation and anion permeability at pH 7 and 4. Addition of salicylate or taurocholate results in stimulation of net Na+ transport. While salicylate and taurocholate increase cation permeability at pH 7, they have differing effects on acid secretion and anion permeability. The data suggest that salicylate and taurocholate alter cation permeability by different mechanisms and are consistent with the concept that enhanced diffusion of H+ into the tissue causes a nonspecific alteration in the permeability pathway."}
{"id": "PMID:3974", "title": "Characteristics of intestinal phase of gastric secretion.", "content": "In four dogs provided with special gastroduodenal fistulas allowing for the complete separation of stomach and duodenum without interrupting the vagal connections between them, the magnitude of the gastric and intestinal phases was compared and their contribution to the total gastric response to a meal was established. A liver extract (LE) meal, confined to the stomach and maintained at pH 5.0 by an intragastric titration technique, produced acid output reaching 66% of the maximal response to histamine (MRH). Perfusion of the LE meal into the duodenum resulted in acid secretion amounting to 57% of MRH. The combination of the gastric and intestinal phases caused the highest acid output, amounting to about 90% of MRH. Gastric and intestinal phases induced separately were accompanied by a significant elevation in serum gastrin concentrations which reached the highest values when both phases were evoked simultaneously. Acidification of the intestinal meal resulted in pH-dependent inhibition of gastric secretion falling to the basal values at pH 1.0. These secretory changes were mimicked by exogenous secretin. Serum gastrin levels remained essentially unaffected by the acidification of the intestinal meal while exogenous secretin significantly lowered them. In conclusion, in the intact stomach with undisturbed nervous connections between the stomach and duodenum, a peptone meal in the intestine is capable of evoking a potent gastric acid and pepsin stimulation by a mechanism involving the release of antral hormone.", "contents": "Characteristics of intestinal phase of gastric secretion. In four dogs provided with special gastroduodenal fistulas allowing for the complete separation of stomach and duodenum without interrupting the vagal connections between them, the magnitude of the gastric and intestinal phases was compared and their contribution to the total gastric response to a meal was established. A liver extract (LE) meal, confined to the stomach and maintained at pH 5.0 by an intragastric titration technique, produced acid output reaching 66% of the maximal response to histamine (MRH). Perfusion of the LE meal into the duodenum resulted in acid secretion amounting to 57% of MRH. The combination of the gastric and intestinal phases caused the highest acid output, amounting to about 90% of MRH. Gastric and intestinal phases induced separately were accompanied by a significant elevation in serum gastrin concentrations which reached the highest values when both phases were evoked simultaneously. Acidification of the intestinal meal resulted in pH-dependent inhibition of gastric secretion falling to the basal values at pH 1.0. These secretory changes were mimicked by exogenous secretin. Serum gastrin levels remained essentially unaffected by the acidification of the intestinal meal while exogenous secretin significantly lowered them. In conclusion, in the intact stomach with undisturbed nervous connections between the stomach and duodenum, a peptone meal in the intestine is capable of evoking a potent gastric acid and pepsin stimulation by a mechanism involving the release of antral hormone."}
{"id": "PMID:3975", "title": "Inhibition of gastric secretion in the dog by 16,16-dimethyl prostaglandin E2.", "content": "The synthetic prostaglandin 16,16-dimethyl E2 (PGE2) given by intravenous infusion at 0.4 mug/kg-h inhibited gastric secretion of H+, K+, Cl-, and pepsin in four fistula dogs stimulated by histamine (H), pentagastrin (P), urecholine (U), and 2-deoxy-D-glucose (2-DG). When given for 90 min during steady infusions of near-maximal doses of H, P, and U, PG-E2 caused 75% inhibition of H+ maximally at 90 min and over 85% inhibition of pepsin secretion maximally at 45 min. Recovery of secretion took 1-2 h after infusion of PGE2 was stopped. Injection of KCl, 1 meq/kg, during inhibition of histamine by PGE2 gave only a 15-min transient reversal in inhibition. When PGE2 was given as background to 45-min step-dose responses, 0.1 mug/kg competitively inhibited histamine stimulation and 0.4 mug/kg-h gave 100% inhibition. Against pentagastrin, 0.1 mug PGE2/kg-h had no effect and 0.4 mug caused uncompetitive inhibition; against urecholine, 0.4 mug PGE2/kg-h caused competitive inhibition of H+ secretion. Pepsin was more markedly inhibited in each case. There were no side effects at either dose of PGE2, which is a potent inhibitor of gastric secretion with all forms of stimuli.", "contents": "Inhibition of gastric secretion in the dog by 16,16-dimethyl prostaglandin E2. The synthetic prostaglandin 16,16-dimethyl E2 (PGE2) given by intravenous infusion at 0.4 mug/kg-h inhibited gastric secretion of H+, K+, Cl-, and pepsin in four fistula dogs stimulated by histamine (H), pentagastrin (P), urecholine (U), and 2-deoxy-D-glucose (2-DG). When given for 90 min during steady infusions of near-maximal doses of H, P, and U, PG-E2 caused 75% inhibition of H+ maximally at 90 min and over 85% inhibition of pepsin secretion maximally at 45 min. Recovery of secretion took 1-2 h after infusion of PGE2 was stopped. Injection of KCl, 1 meq/kg, during inhibition of histamine by PGE2 gave only a 15-min transient reversal in inhibition. When PGE2 was given as background to 45-min step-dose responses, 0.1 mug/kg competitively inhibited histamine stimulation and 0.4 mug/kg-h gave 100% inhibition. Against pentagastrin, 0.1 mug PGE2/kg-h had no effect and 0.4 mug caused uncompetitive inhibition; against urecholine, 0.4 mug PGE2/kg-h caused competitive inhibition of H+ secretion. Pepsin was more markedly inhibited in each case. There were no side effects at either dose of PGE2, which is a potent inhibitor of gastric secretion with all forms of stimuli."}
{"id": "PMID:3976", "title": "Effect of carbon monoxide on equilibrium between oxygen and hemoglobin.", "content": "Oxygen dissociation curves of partially CO-saturated human whole blood drawn freshly or preserved more than 3 wk were studied. With increasing CO-hemoglobin concentrations, oxygen affinity of the blood increased and the Hill coefficient, n, fell and gradually approached unity. The changes induced by CO-hemoglobin showed practically no difference in the presence or absence of 2,3-diphosphoglycerate. The Bohr coefficient, deltalog P50/deltapH, was determined as a function of oxygen saturation for various concentrations of CO-hemoglobin. The coefficient remained essentially unchanged in the presence of CO-hemoglobin. In the presence of less than 50% CO-hemoglobin, a good agreement was observed between the observed oxygen dissociation curves and the curves calculated according to Roughton and Darling (Am. J. Physiol. 141: 17-31, 1944). Based on these results, physiological implications of carboxyhemoglobinemia are discussed quantitatively in comparison with methemoglobinemia.", "contents": "Effect of carbon monoxide on equilibrium between oxygen and hemoglobin. Oxygen dissociation curves of partially CO-saturated human whole blood drawn freshly or preserved more than 3 wk were studied. With increasing CO-hemoglobin concentrations, oxygen affinity of the blood increased and the Hill coefficient, n, fell and gradually approached unity. The changes induced by CO-hemoglobin showed practically no difference in the presence or absence of 2,3-diphosphoglycerate. The Bohr coefficient, deltalog P50/deltapH, was determined as a function of oxygen saturation for various concentrations of CO-hemoglobin. The coefficient remained essentially unchanged in the presence of CO-hemoglobin. In the presence of less than 50% CO-hemoglobin, a good agreement was observed between the observed oxygen dissociation curves and the curves calculated according to Roughton and Darling (Am. J. Physiol. 141: 17-31, 1944). Based on these results, physiological implications of carboxyhemoglobinemia are discussed quantitatively in comparison with methemoglobinemia."}
{"id": "PMID:3977", "title": "Erythropoietin production after renal denervation or beta-adrenergic blockade.", "content": "The ability of either beta-adrenergic blockade or bilateral renal denervation to alter erythropoietin (ESF) production in rabbits exposed to hypobaric hypoxia was studied. ESF elaboration during 5 h of exposure to hypoxia was not affected by beta-blockade, but was markedly reduced by prior surgical denervation of both kidneys. After 18 h of hypoxia plasma ESF levels in renal denervated rabbits did not differ significantly from those of sham-operated controls. Previous studies have shown that ESF production during this more prolonged exposure to hypoxia was significantly inhibited by some beta-adrenergic blocking agents. Combined renal denervation and beta-blockade were more effective than renal denervation alone in attenuating ESF production during 5 h of exposure to hypoxia. However, ESF elaboration during 18 h of hypoxia was significantly greater in animals with combined denervation and beta-blockade than in control rabbits. These results suggest the existence of two distinct mechanisms for ESF production in rabbits exposed to hypobaric hypoxia.", "contents": "Erythropoietin production after renal denervation or beta-adrenergic blockade. The ability of either beta-adrenergic blockade or bilateral renal denervation to alter erythropoietin (ESF) production in rabbits exposed to hypobaric hypoxia was studied. ESF elaboration during 5 h of exposure to hypoxia was not affected by beta-blockade, but was markedly reduced by prior surgical denervation of both kidneys. After 18 h of hypoxia plasma ESF levels in renal denervated rabbits did not differ significantly from those of sham-operated controls. Previous studies have shown that ESF production during this more prolonged exposure to hypoxia was significantly inhibited by some beta-adrenergic blocking agents. Combined renal denervation and beta-blockade were more effective than renal denervation alone in attenuating ESF production during 5 h of exposure to hypoxia. However, ESF elaboration during 18 h of hypoxia was significantly greater in animals with combined denervation and beta-blockade than in control rabbits. These results suggest the existence of two distinct mechanisms for ESF production in rabbits exposed to hypobaric hypoxia."}
{"id": "PMID:3978", "title": "The current status of behavioral psychotherapy: theory and practice.", "content": "Behavioral psychotherapy has become one of the definitive treatments available for the relief of psychiatric suffering. Although hardly a panacea for all ills, the behavioral approach is the treatment of choice for certain selected problems. Behavioral methods make their contribution in the context of general psychiatric management and often must be used in conjunction with other treatment. The theoretical and practical aspects of behavioral psychotherapy have changed a great deal over the past few years and continue to evolve rapidly. Although useful molecular theories are emerging to guide the discipline, no global theory is likely to be satisfactory in the foreseeable future.", "contents": "The current status of behavioral psychotherapy: theory and practice. Behavioral psychotherapy has become one of the definitive treatments available for the relief of psychiatric suffering. Although hardly a panacea for all ills, the behavioral approach is the treatment of choice for certain selected problems. Behavioral methods make their contribution in the context of general psychiatric management and often must be used in conjunction with other treatment. The theoretical and practical aspects of behavioral psychotherapy have changed a great deal over the past few years and continue to evolve rapidly. Although useful molecular theories are emerging to guide the discipline, no global theory is likely to be satisfactory in the foreseeable future."}
{"id": "PMID:3979", "title": "Effect of drug ritual changes on schizophrenic patients.", "content": "The author evaluated the charts of 115 chronic schizophrenic patients who regularly attended a follow-up group to determine whether changes in long-standing medication regimens produced an increased dropout rate, decreased attendance, or psychotic decompensation. He found that although there were nonsignificant trends showing a relationship between medication change and group attendance for individual patients, there were no significant difference between group attendance and change or no change in medication routine for the group of patients as a whole. He concludes that necessary changes in medication routines for chronic schizophrenic patients are safe.", "contents": "Effect of drug ritual changes on schizophrenic patients. The author evaluated the charts of 115 chronic schizophrenic patients who regularly attended a follow-up group to determine whether changes in long-standing medication regimens produced an increased dropout rate, decreased attendance, or psychotic decompensation. He found that although there were nonsignificant trends showing a relationship between medication change and group attendance for individual patients, there were no significant difference between group attendance and change or no change in medication routine for the group of patients as a whole. He concludes that necessary changes in medication routines for chronic schizophrenic patients are safe."}
{"id": "PMID:3980", "title": "A simple technique for demonstrating transmission of dengue virus by mosquitoes without the use of vertebrate hosts.", "content": "Aedes albopictus mosquitoes infected with dengue type 2 virus transmitted virus to measured small amounts of fluid which could be titrated readily for virus content. It was found that the percentage of mosquitoes transmitting was related to the extent of salivary gland infection. It was not uncommon for mosquitoes to transmit as much as 10(4) mosquito infectious doses50 of virus and transmission of significant amounts of virus was observed even though an insect only probed the test suspension without feeding to repletion. Transmission of virus was demonstrated as early as 10 days after oral infection when mosquitoes were held at 32 degrees C.", "contents": "A simple technique for demonstrating transmission of dengue virus by mosquitoes without the use of vertebrate hosts. Aedes albopictus mosquitoes infected with dengue type 2 virus transmitted virus to measured small amounts of fluid which could be titrated readily for virus content. It was found that the percentage of mosquitoes transmitting was related to the extent of salivary gland infection. It was not uncommon for mosquitoes to transmit as much as 10(4) mosquito infectious doses50 of virus and transmission of significant amounts of virus was observed even though an insect only probed the test suspension without feeding to repletion. Transmission of virus was demonstrated as early as 10 days after oral infection when mosquitoes were held at 32 degrees C."}
{"id": "PMID:3981", "title": "Ecologic studies of Venezuelan encephalitis virus and isolations of Nepuyo and Patois viruses during 1968-1973 at a marsh habitat near the epicenter of the 1969 outbreak in Guatemala.", "content": "Ecologic studies of Venezuelan encephalitis (VE) virus at a marsh habitat near the epicenter of the 1969 outbreak in Guatemala revealed that the virus was enzootic there. VE virus was isolated yearly during 1968-1973 from sentinel hamsters exposed during the rainy seasons and from mosquitoes collected during July and August 1970. Hamsters yielded 41 strains of VE virus and virus was detected within 2 km of the edge of the marsh, in its interior, and at its western extreme 18 km from the central study site at La Avellana. One strain of virus came from a hamster that died in the dry season of January 1970. Culex mosquitoes yielded 20 strains of VE virus and Mansonia and Aedes one each. Culex (Melanoconion) and Aedes taeniorhynchus were most prevalent near the marsh. Hemagglutination-inhitibion (HI) and neutralization antibody tests of sera showed that wild terrestrial mammals (opossums and rodents), humans, and dogs, but not wild birds, were frequently infected. Seven of 16 susceptible residents of villages at the edge of the marsh developed antibodies without symptoms during an 18-month period between September 1971 and February 1973. Only 1 of 5 sentinel rabbits, and none of 30 sentinel chickens developed VE HI antibody during August-September 1971, a period when virus activity was readily detected by the use of sentinel hamsters. Five strains of group C arbovirus (one identified as Nepuyo) were recovered from sentinel hamsters during 1968 to 1970, and one strain of Nepuyo virus was isolated from the blood of a person with a febrile illness during 1972. Two strains of Patois group arboviruses were isolated from Culex mosquitoes during 1970.", "contents": "Ecologic studies of Venezuelan encephalitis virus and isolations of Nepuyo and Patois viruses during 1968-1973 at a marsh habitat near the epicenter of the 1969 outbreak in Guatemala. Ecologic studies of Venezuelan encephalitis (VE) virus at a marsh habitat near the epicenter of the 1969 outbreak in Guatemala revealed that the virus was enzootic there. VE virus was isolated yearly during 1968-1973 from sentinel hamsters exposed during the rainy seasons and from mosquitoes collected during July and August 1970. Hamsters yielded 41 strains of VE virus and virus was detected within 2 km of the edge of the marsh, in its interior, and at its western extreme 18 km from the central study site at La Avellana. One strain of virus came from a hamster that died in the dry season of January 1970. Culex mosquitoes yielded 20 strains of VE virus and Mansonia and Aedes one each. Culex (Melanoconion) and Aedes taeniorhynchus were most prevalent near the marsh. Hemagglutination-inhitibion (HI) and neutralization antibody tests of sera showed that wild terrestrial mammals (opossums and rodents), humans, and dogs, but not wild birds, were frequently infected. Seven of 16 susceptible residents of villages at the edge of the marsh developed antibodies without symptoms during an 18-month period between September 1971 and February 1973. Only 1 of 5 sentinel rabbits, and none of 30 sentinel chickens developed VE HI antibody during August-September 1971, a period when virus activity was readily detected by the use of sentinel hamsters. Five strains of group C arbovirus (one identified as Nepuyo) were recovered from sentinel hamsters during 1968 to 1970, and one strain of Nepuyo virus was isolated from the blood of a person with a febrile illness during 1972. Two strains of Patois group arboviruses were isolated from Culex mosquitoes during 1970."}
{"id": "PMID:3982", "title": "Studies of possible movement of Venezuelan encephalitis virus from an enzootic focus in Guatemala during 1971-1974.", "content": "During the wet seasons of 1972 and possibly 1971, sentinel horses became infected by Venezuelan encephalitis (VE) virus in a temporally and geographically progressive manner inland from an enzootic marsh focus of virus on the Pacific couast of southeastern Guatemala. During the wet seasons of 1972 and 1973, VE virus was detected by sentinel horses (and a sentinel hamster in 1972) in a small woods 10 km north of the marsh, but virus was undetectable there during the dry seasons of 1973 and 1974 and the wet season of 1974. Culex (Melanoconion) mosquitoes were found in this woods and at the marsh during August 1973. These observations are compatible with movement of VE virus from the marsh habitat during some wet seasons. However, virus activity in this region adjacent to the marsh was quantitatively unpredictable on a yearly basis and occurred in only very focal habitats during 1971 to 1974. Mechanisms of VE virus movement from the marsh are currently unknown, but bats are under study as a likely possibility.", "contents": "Studies of possible movement of Venezuelan encephalitis virus from an enzootic focus in Guatemala during 1971-1974. During the wet seasons of 1972 and possibly 1971, sentinel horses became infected by Venezuelan encephalitis (VE) virus in a temporally and geographically progressive manner inland from an enzootic marsh focus of virus on the Pacific couast of southeastern Guatemala. During the wet seasons of 1972 and 1973, VE virus was detected by sentinel horses (and a sentinel hamster in 1972) in a small woods 10 km north of the marsh, but virus was undetectable there during the dry seasons of 1973 and 1974 and the wet season of 1974. Culex (Melanoconion) mosquitoes were found in this woods and at the marsh during August 1973. These observations are compatible with movement of VE virus from the marsh habitat during some wet seasons. However, virus activity in this region adjacent to the marsh was quantitatively unpredictable on a yearly basis and occurred in only very focal habitats during 1971 to 1974. Mechanisms of VE virus movement from the marsh are currently unknown, but bats are under study as a likely possibility."}
{"id": "PMID:3983", "title": "Hepatitis B surface antigen (Australia antigen) in mosquitoes collected in Senegal, West Africa.", "content": "During July and August of 1973, 9,198 mosquitoes were collected in the Republic of Senegal. Eight species of mosquitoes were found in the collections: Culex thalassius, Culex pipiens quinquefasciatus, Culex trigripes, Culex phillipi, Aedes irritans, Aedes aegypti, Anopheles gambiae, and Mansonia sp. Specimens were sorted by biological condition; those obviously engorged were designated as (E), females with swollen abdomens not conspicuously blooded were considered gravid (G), and those with normal or shrunken abdomens were considered neither blooded nor gravid (U). Representative samples of each species were tested by solid phase radioimmunoassay for hepatitis B surface antigen (HBSAg, Australia antigen). A total of 12 mosquitoes were found to be HBSAg positive out of 1,658 individuals tested. These were: 9 Culex thalassius, 1 (E), 5 (G), 3 (U); 2 Culex pipiens quinquefasciatus, 1 (E), 1 (U); and Aedes irritans, 1 (U).", "contents": "Hepatitis B surface antigen (Australia antigen) in mosquitoes collected in Senegal, West Africa. During July and August of 1973, 9,198 mosquitoes were collected in the Republic of Senegal. Eight species of mosquitoes were found in the collections: Culex thalassius, Culex pipiens quinquefasciatus, Culex trigripes, Culex phillipi, Aedes irritans, Aedes aegypti, Anopheles gambiae, and Mansonia sp. Specimens were sorted by biological condition; those obviously engorged were designated as (E), females with swollen abdomens not conspicuously blooded were considered gravid (G), and those with normal or shrunken abdomens were considered neither blooded nor gravid (U). Representative samples of each species were tested by solid phase radioimmunoassay for hepatitis B surface antigen (HBSAg, Australia antigen). A total of 12 mosquitoes were found to be HBSAg positive out of 1,658 individuals tested. These were: 9 Culex thalassius, 1 (E), 5 (G), 3 (U); 2 Culex pipiens quinquefasciatus, 1 (E), 1 (U); and Aedes irritans, 1 (U)."}
{"id": "PMID:3984", "title": "Hemorrhagic shock in dogs. Comparison of treatment with shed blood alone versus shed blood plus Ringer's lactate: intravascular pressures, cardiac output, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2, electrolyte changes, and survival rates.", "content": "The purpose of our study of hemorrhagic shock in dogs was to examine the efficacy of adding Ringer's lactate to shed blood replacement in increasing animal rates. The standard Wiggers' hemorrhagic shock technic was used in two groups of ten animals each. Intravascular pressures, cardiac outut, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2 and pH, electrolyte changes, and survival rates were determined. There was a positive correlation between changes in cardiac output, central venous oxygen content, and PO2 and extracellular fluid PO2 as measured using subcutaneously implanted Silastic tubing and perforated plastic balls. Four of the dogs that received shed blood alone survived, whereas five of the dogs that received shed blood plus Ringer's lactate survived. This difference was not statistically significant.", "contents": "Hemorrhagic shock in dogs. Comparison of treatment with shed blood alone versus shed blood plus Ringer's lactate: intravascular pressures, cardiac output, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2, electrolyte changes, and survival rates. The purpose of our study of hemorrhagic shock in dogs was to examine the efficacy of adding Ringer's lactate to shed blood replacement in increasing animal rates. The standard Wiggers' hemorrhagic shock technic was used in two groups of ten animals each. Intravascular pressures, cardiac outut, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2 and pH, electrolyte changes, and survival rates were determined. There was a positive correlation between changes in cardiac output, central venous oxygen content, and PO2 and extracellular fluid PO2 as measured using subcutaneously implanted Silastic tubing and perforated plastic balls. Four of the dogs that received shed blood alone survived, whereas five of the dogs that received shed blood plus Ringer's lactate survived. This difference was not statistically significant."}
{"id": "PMID:3986", "title": "[Conformational changes of hyaluronic acid in acid medium (author's transl)].", "content": "Both vitreous body homogenate and a fibrous product containing hyaluronic acid and collagen isolated from vitreous humor by acetone precipitation were investigated to elucidate the liquefaction of vitreous body by acids. Graphic evaluation of the titration with hydrochlorid acid and viscosity measurements suggest a changed of the hyaluronic acid molecule in the pH-range between 5.2 and 4.1. Between these pH-values the ionization of carboxyl groups is decreased accompanied by conformational changes of the hyaluronic acid molecule. These results are in agreement with the conclusion of other authors that by lowering the pH of hyaluronic acid solutions a random coil to double helix transition of hyaluronic acid occurs.", "contents": "[Conformational changes of hyaluronic acid in acid medium (author's transl)]. Both vitreous body homogenate and a fibrous product containing hyaluronic acid and collagen isolated from vitreous humor by acetone precipitation were investigated to elucidate the liquefaction of vitreous body by acids. Graphic evaluation of the titration with hydrochlorid acid and viscosity measurements suggest a changed of the hyaluronic acid molecule in the pH-range between 5.2 and 4.1. Between these pH-values the ionization of carboxyl groups is decreased accompanied by conformational changes of the hyaluronic acid molecule. These results are in agreement with the conclusion of other authors that by lowering the pH of hyaluronic acid solutions a random coil to double helix transition of hyaluronic acid occurs."}
{"id": "PMID:3987", "title": "Treatment of the diving casualty.", "content": "In a diving emergency a number of specific conditions are possible in addition to those which would ordinarily be considered in a life-threatening situation. There are many separate factors which, underwater, can lead by some unfortunate combination of circumstances towards death usually, but not always, by drowning. The other major category of accidents are those resulting from the ascent of the diver to the surface. These must be considered as medical emergencies and the majority respond to immediate recompression. In the absence of readily available recompression facilities,various measures may ameliorate the condition pending transfer to a suitable compression chamber.", "contents": "Treatment of the diving casualty. In a diving emergency a number of specific conditions are possible in addition to those which would ordinarily be considered in a life-threatening situation. There are many separate factors which, underwater, can lead by some unfortunate combination of circumstances towards death usually, but not always, by drowning. The other major category of accidents are those resulting from the ascent of the diver to the surface. These must be considered as medical emergencies and the majority respond to immediate recompression. In the absence of readily available recompression facilities,various measures may ameliorate the condition pending transfer to a suitable compression chamber."}
{"id": "PMID:3992", "title": "Scanning electron microscopic study of chylomicrons incubated with lipoprotein lipase.", "content": "The effects of lipolysis on the structure of chylomicrons were studied with the scanning electron microscope using rat chylomicrons incubated with purified bovine milk lipoprotein lipase for 20 minutes at pH 8.1. Since the amount of albumin added to the medium was limited, some of the free fatty acids and partial glycerides formed by lipolysis accumulated in the chylomicrons. Lipolyzed chylomicrons fixed with OSO4 at pH 7.4 appeared in scanning electron micrographs as spheres with multiply idented irregular surfaces, while those fixed at pH 5.5, AS WELL AS CONTROL CHYLOMICRONS FIXED AT BOTH PHs, appeared as spheres with smooth surfaces. Sections of OSO4-fixed specimens, viewed with the transmission electron microscope, showed that the core of lipolyzed chylomicrons fixed at pH 7.4 contained numerous circular electron-lucent areas at the periphery, thus accounting for the indented surfaces observed above, while the core surfaces of the other specimens were circular and smooth. These findings confirm an earlier report that aqueous spaces form in chylomicrons during lipolysis when albumin in the medium is limited, and that the aqueous spaces disappear when specimens are prepared at pH 5.5 for microscopy. Thin sections of specimens that had been prepared for scanning electron microscopy showed that the gold-palladium coating was desposited directly on the indented surface of the lipid core of lipolyzed chylomicrons fixed at pH 7.4. It is concluded that vacuum dehydration during specimen preparation ruptures the outer wall of the aqueous spaces in lipolyzed chylomicrons and thereby exposes the interior of the spaces to gold-palladium coating and viewing with the scanning electron microscope.", "contents": "Scanning electron microscopic study of chylomicrons incubated with lipoprotein lipase. The effects of lipolysis on the structure of chylomicrons were studied with the scanning electron microscope using rat chylomicrons incubated with purified bovine milk lipoprotein lipase for 20 minutes at pH 8.1. Since the amount of albumin added to the medium was limited, some of the free fatty acids and partial glycerides formed by lipolysis accumulated in the chylomicrons. Lipolyzed chylomicrons fixed with OSO4 at pH 7.4 appeared in scanning electron micrographs as spheres with multiply idented irregular surfaces, while those fixed at pH 5.5, AS WELL AS CONTROL CHYLOMICRONS FIXED AT BOTH PHs, appeared as spheres with smooth surfaces. Sections of OSO4-fixed specimens, viewed with the transmission electron microscope, showed that the core of lipolyzed chylomicrons fixed at pH 7.4 contained numerous circular electron-lucent areas at the periphery, thus accounting for the indented surfaces observed above, while the core surfaces of the other specimens were circular and smooth. These findings confirm an earlier report that aqueous spaces form in chylomicrons during lipolysis when albumin in the medium is limited, and that the aqueous spaces disappear when specimens are prepared at pH 5.5 for microscopy. Thin sections of specimens that had been prepared for scanning electron microscopy showed that the gold-palladium coating was desposited directly on the indented surface of the lipid core of lipolyzed chylomicrons fixed at pH 7.4. It is concluded that vacuum dehydration during specimen preparation ruptures the outer wall of the aqueous spaces in lipolyzed chylomicrons and thereby exposes the interior of the spaces to gold-palladium coating and viewing with the scanning electron microscope."}
{"id": "PMID:3995", "title": "Effects of training on biochemical values in standardbred horses.", "content": "Effects of training at a regular, fixed, standard exercise load on venous lactic acid, mixed venous and arterial blood gases and pH, and serum muscle enzymes were determined on previously unconditioned, healthy, adult, Standardbred horses. Arterial and mixed venous blood gases, pH, and serum muscle enzymes did not change in a consistent manner during training. Venous lactic acid concentrations did increase significantly with training and may be of value for the biochemical evaluation of fitness in horses.", "contents": "Effects of training on biochemical values in standardbred horses. Effects of training at a regular, fixed, standard exercise load on venous lactic acid, mixed venous and arterial blood gases and pH, and serum muscle enzymes were determined on previously unconditioned, healthy, adult, Standardbred horses. Arterial and mixed venous blood gases, pH, and serum muscle enzymes did not change in a consistent manner during training. Venous lactic acid concentrations did increase significantly with training and may be of value for the biochemical evaluation of fitness in horses."}
{"id": "PMID:3996", "title": "Acid-base values of standardbred horses recovering from strenuous exercise.", "content": "Blood gases, lactic acid concentrations, and pH were measured in arterial and mixed venous blood in moderately conditioned Standardbred horses after a standardized exercise load of 1.6 km in 2 minutes, 40 seconds. Samples were obtained at rest, immediately after exercise, and at 3, 6, 15, 30, and 60 minutes after exercise. Arterial oxygen tension and mixed venous oxygen tension increased after exercise, reaching peak values at 6 minutes. Arterial oxygen tension returned to the resting (preexercise) value by 15 minutes, and mixed venous oxygen tension by 30 minutes. Arterial carbon dioxide tension decreased immediately after exercise, reaching its lowest value at 6 minutes, and returned to resting value by 30 minutes. Mixed venous carbon dioxide tension reached its highest value immediately after exercise, then decreased to less than the resting value, reaching its lowest value by 15 minutes, and returned to normal by 60 minutes. Lactic acid concentration increased immediately after exercise, reaching its highest value at 6 minutes, and returned toward normal by 60 minutes. Arterial pH decreased immediately after exercise, reaching its lowest value at 6 minutes, and returned to normal by 60 minutes. Mixed venous pH reached its lowest value immediately after exercise, then began to increase, and returned to normal by 60 minutes. The decrease in mixed venous pH was more pronounced than that in arterial blood since, in addition to the increase in lartic acid, there was a considerable increase in mixed venous carbon dioxide tension.", "contents": "Acid-base values of standardbred horses recovering from strenuous exercise. Blood gases, lactic acid concentrations, and pH were measured in arterial and mixed venous blood in moderately conditioned Standardbred horses after a standardized exercise load of 1.6 km in 2 minutes, 40 seconds. Samples were obtained at rest, immediately after exercise, and at 3, 6, 15, 30, and 60 minutes after exercise. Arterial oxygen tension and mixed venous oxygen tension increased after exercise, reaching peak values at 6 minutes. Arterial oxygen tension returned to the resting (preexercise) value by 15 minutes, and mixed venous oxygen tension by 30 minutes. Arterial carbon dioxide tension decreased immediately after exercise, reaching its lowest value at 6 minutes, and returned to resting value by 30 minutes. Mixed venous carbon dioxide tension reached its highest value immediately after exercise, then decreased to less than the resting value, reaching its lowest value by 15 minutes, and returned to normal by 60 minutes. Lactic acid concentration increased immediately after exercise, reaching its highest value at 6 minutes, and returned toward normal by 60 minutes. Arterial pH decreased immediately after exercise, reaching its lowest value at 6 minutes, and returned to normal by 60 minutes. Mixed venous pH reached its lowest value immediately after exercise, then began to increase, and returned to normal by 60 minutes. The decrease in mixed venous pH was more pronounced than that in arterial blood since, in addition to the increase in lartic acid, there was a considerable increase in mixed venous carbon dioxide tension."}
{"id": "PMID:3993", "title": "[Metabolic acidosis and intravenous injections of fat emulsions (role of phospholipids. Experimental study)].", "content": "In explanation of metabolic acidosis during parenteral nutrition, the authors considered the supply of H+ ions by fat emulsion, containing phospholipids of egg or soy. During intravenous infusions of 24 grams of lecithins to two healthy subjects, they observed an increased output H+ ions in urine, about 74,05 and 75,88 mEq, and a metabolic acidosis of the plasma. The theorically forcasted supply of production was 74,6 mEq. Indeed the metabolism of phospholipids supplies phosphoric ions (PO4H3), giving H+ ions at pH 7,40. The most used fat emulsions are able to give between 37 (intralipid 10%) and 61 (lipihysan 15%) mEq of H+ ions/liter.", "contents": "[Metabolic acidosis and intravenous injections of fat emulsions (role of phospholipids. Experimental study)]. In explanation of metabolic acidosis during parenteral nutrition, the authors considered the supply of H+ ions by fat emulsion, containing phospholipids of egg or soy. During intravenous infusions of 24 grams of lecithins to two healthy subjects, they observed an increased output H+ ions in urine, about 74,05 and 75,88 mEq, and a metabolic acidosis of the plasma. The theorically forcasted supply of production was 74,6 mEq. Indeed the metabolism of phospholipids supplies phosphoric ions (PO4H3), giving H+ ions at pH 7,40. The most used fat emulsions are able to give between 37 (intralipid 10%) and 61 (lipihysan 15%) mEq of H+ ions/liter."}
{"id": "PMID:3997", "title": "Identification of immunoglobulins associated with complement fixation, agglutination, and low pH buffered antigen tests for brucellosis.", "content": "Serums from infected cattle, cattle with persistent postvaccinal antibody, and serologically \"positive\" noninfected cattle were fractionated into major immunoglobulin classes by diethylaminoethyl (DEAE)-cellulose chromatography and by sucrose density gradient centrifugation. Each fraction was assayed for anti-Brucella activity by standard tube-agglutination test (STT), buffered tube-agglutination test (BTT), and complement-fixation test (CF). In the serums from experimentally infected cattle, anti-Brucella antibody could be found by all tests in 6 DEAE fractions and in slow, fast, and sediment regions of the density gradient. Serums from cattle with persistent postvaccinal titers had STT activity in all 6 DEAE fractions, BTT activity in 5 fractions, and CF activity in only 1 fraction. The STT and BTT activities were found in the slow and the sediment regions of the gradient, whereas the CF activity was found only in the slow region. Serums from a chronically infected animal had STT and BTT activities in 2 DEAE fractions and CF activity in only 1. The STT, BTT, and CF activities were found in the slow and the sediment regions of the gradient. The principal antibody in serums from noninfected cattle was immunoglobulin M, which had all of the CF activity and most of the STT and BTT activities. Low levels of STT and BTT activities were found in 3 other DEAE fractions. Only STT and BTT activities were found in the fast and the sediment regions of the gradient.", "contents": "Identification of immunoglobulins associated with complement fixation, agglutination, and low pH buffered antigen tests for brucellosis. Serums from infected cattle, cattle with persistent postvaccinal antibody, and serologically \"positive\" noninfected cattle were fractionated into major immunoglobulin classes by diethylaminoethyl (DEAE)-cellulose chromatography and by sucrose density gradient centrifugation. Each fraction was assayed for anti-Brucella activity by standard tube-agglutination test (STT), buffered tube-agglutination test (BTT), and complement-fixation test (CF). In the serums from experimentally infected cattle, anti-Brucella antibody could be found by all tests in 6 DEAE fractions and in slow, fast, and sediment regions of the density gradient. Serums from cattle with persistent postvaccinal titers had STT activity in all 6 DEAE fractions, BTT activity in 5 fractions, and CF activity in only 1 fraction. The STT and BTT activities were found in the slow and the sediment regions of the gradient, whereas the CF activity was found only in the slow region. Serums from a chronically infected animal had STT and BTT activities in 2 DEAE fractions and CF activity in only 1. The STT, BTT, and CF activities were found in the slow and the sediment regions of the gradient. The principal antibody in serums from noninfected cattle was immunoglobulin M, which had all of the CF activity and most of the STT and BTT activities. Low levels of STT and BTT activities were found in 3 other DEAE fractions. Only STT and BTT activities were found in the fast and the sediment regions of the gradient."}
{"id": "PMID:3994", "title": "Theoretic significance of pH dependence of narcotics and narcotic antagonists in clinical anesthesia.", "content": "Determination of the effect of pH and temperature on pKa partition, and drug distribution coefficients in a series of common narcotics and their antagonists has shown that within the range of blood pH (7.1 to 7.7) encountered in the practice of anesthesiology, marked differences of distribution of the drugs between a model lipid (octanol) and water can occur. When these data are considered in the light of clinical experience with narcotics used in patients undergoing or recovering from surgical procedures, a correlation between the depth and duration of narcosis or the efficacy of narcotic antidotes and ventilatory status is seen. This correlation can be explained in part if the influence of blood pH on the probable CNS/blood distribution of a given drug is taken into consideration. Support is given to this proposal by representative studies in the literature. The very different drug distribution coefficients of two closely related narcotic antagonists, naloxone and naltrexone, correctly predicted the faster onset and shorter duration of the former, which was confirmed by reported clinical observations.", "contents": "Theoretic significance of pH dependence of narcotics and narcotic antagonists in clinical anesthesia. Determination of the effect of pH and temperature on pKa partition, and drug distribution coefficients in a series of common narcotics and their antagonists has shown that within the range of blood pH (7.1 to 7.7) encountered in the practice of anesthesiology, marked differences of distribution of the drugs between a model lipid (octanol) and water can occur. When these data are considered in the light of clinical experience with narcotics used in patients undergoing or recovering from surgical procedures, a correlation between the depth and duration of narcosis or the efficacy of narcotic antidotes and ventilatory status is seen. This correlation can be explained in part if the influence of blood pH on the probable CNS/blood distribution of a given drug is taken into consideration. Support is given to this proposal by representative studies in the literature. The very different drug distribution coefficients of two closely related narcotic antagonists, naloxone and naltrexone, correctly predicted the faster onset and shorter duration of the former, which was confirmed by reported clinical observations."}
{"id": "PMID:3999", "title": "\"Aspiration disease\".", "content": "Aspiration disease, a term used to define both an acute and chronic form of a disease entity, is described. Etiological factors, pathophysiology and therapy are discussed with emphasis on aspiration of gastric juice. A brief mention of a small clinical experience is included.", "contents": "\"Aspiration disease\". Aspiration disease, a term used to define both an acute and chronic form of a disease entity, is described. Etiological factors, pathophysiology and therapy are discussed with emphasis on aspiration of gastric juice. A brief mention of a small clinical experience is included."}
{"id": "PMID:4010", "title": "Plasmid-mediated penicillin beta-lactamases in Pseudomonas aeruginosa.", "content": "A penicillin beta-lactamase (PCase) was extracted from Pseudomonas aeruginosa Rms139(+) and purified by means of column chromatography. The isoelectric point of Rms139 PCase was 5.7 and its molecular weight was 22,500 +/- 1,000. The optimal pH for the hydrolysis of benzylpenicillin was 7.0 to 7.5 and the optimal temperature was 45 C, with the PCase also showing high activity against carbenicillin. It is concluded that this enzyme is a new type of penicillin beta-lactamase different from the type I, II, or III R plasmid-mediated PCases reported previously.", "contents": "Plasmid-mediated penicillin beta-lactamases in Pseudomonas aeruginosa. A penicillin beta-lactamase (PCase) was extracted from Pseudomonas aeruginosa Rms139(+) and purified by means of column chromatography. The isoelectric point of Rms139 PCase was 5.7 and its molecular weight was 22,500 +/- 1,000. The optimal pH for the hydrolysis of benzylpenicillin was 7.0 to 7.5 and the optimal temperature was 45 C, with the PCase also showing high activity against carbenicillin. It is concluded that this enzyme is a new type of penicillin beta-lactamase different from the type I, II, or III R plasmid-mediated PCases reported previously."}
{"id": "PMID:4011", "title": "Immunosuppressant activity of the ansamycins.", "content": "The immunosuppressive effect of four analogues of rifampin and two streptovaracins on cell-mediated immunity has been determined. Tuberculin hypersensitivity in the footpads of immunized mice was inhibited by three of the rifampin analogues and by both streptovaracins. The observed in vivo immunosuppressive activity of the compounds tested was not correlated with their in vitro activity against mycobacterial growth but was associated with their toxicity in mice. These data indicate that some of the analogues of rifampin and the streptovaracins can significantly suppress cell-mediated immunity and suggest that other ansamycins may have significant immunosuppressant activity.", "contents": "Immunosuppressant activity of the ansamycins. The immunosuppressive effect of four analogues of rifampin and two streptovaracins on cell-mediated immunity has been determined. Tuberculin hypersensitivity in the footpads of immunized mice was inhibited by three of the rifampin analogues and by both streptovaracins. The observed in vivo immunosuppressive activity of the compounds tested was not correlated with their in vitro activity against mycobacterial growth but was associated with their toxicity in mice. These data indicate that some of the analogues of rifampin and the streptovaracins can significantly suppress cell-mediated immunity and suggest that other ansamycins may have significant immunosuppressant activity."}
{"id": "PMID:4012", "title": "In vitro susceptibility studies with josamycin and erythromycin.", "content": "The in vitro activity of josamycin and erythromycin against five bacterial species was compared. In general, erythromycin was slightly more active by weight than josamycin, although both agents had a similar range of activity.", "contents": "In vitro susceptibility studies with josamycin and erythromycin. The in vitro activity of josamycin and erythromycin against five bacterial species was compared. In general, erythromycin was slightly more active by weight than josamycin, although both agents had a similar range of activity."}
{"id": "PMID:4036", "title": "Two XX males diagnosed in childhood. Endocrine, renal, and laboratory findings.", "content": "Two prepubertal boys with bilateral cryptorchidism were identified as 46,XX after nuclear sexing studies in several tissues. Gonadal histology and chromosome studies suggested that true hermaphroditism or mosaicism were unlikely. Xg blood grouping was informative in one patient. Accepting paternity, this suggested either that both Xs were maternal, with loss, for example, of the male determining Y chromosome, or that the paternal X chromosome did not express, probably because of a deletion, the allele for the positive Xg blood group. The patients had normal thyroid stimulating hormone reserves but subnormal responses to human chorionic gonadotrophin stimulation, and may need hormonal replacement at puberty. Both had renal anomalies. We suggest that chromosome analysis is essential when cryptorchidism, hypospadias, or microgenitalia are found and that an intravenous pyelogram is desirable.", "contents": "Two XX males diagnosed in childhood. Endocrine, renal, and laboratory findings. Two prepubertal boys with bilateral cryptorchidism were identified as 46,XX after nuclear sexing studies in several tissues. Gonadal histology and chromosome studies suggested that true hermaphroditism or mosaicism were unlikely. Xg blood grouping was informative in one patient. Accepting paternity, this suggested either that both Xs were maternal, with loss, for example, of the male determining Y chromosome, or that the paternal X chromosome did not express, probably because of a deletion, the allele for the positive Xg blood group. The patients had normal thyroid stimulating hormone reserves but subnormal responses to human chorionic gonadotrophin stimulation, and may need hormonal replacement at puberty. Both had renal anomalies. We suggest that chromosome analysis is essential when cryptorchidism, hypospadias, or microgenitalia are found and that an intravenous pyelogram is desirable."}
{"id": "PMID:4039", "title": "Establishment of a viable homograft cardiac valve bank: a rapid method of determining homograft viability.", "content": "A method for determining the viability of homograft valves has been developed based on sequential measurements of glucose and pH levels of the culture medium in which cardiac valves have been maintained for short periods at 37 degrees C. Viable valves, as determined by tissue culture, showed a characteristic pattern of glucose utilization and pH reduction that was absent in nonviable valves. Upon explantation of valve leaflet fragments into tissue culture, only fragments from valves that metabolized glucose produced viable fibroblast cultures. The method reported here is rapid, requires no specialized equipment, is nondestructive, and can directly determine the viability of the valve homograft within 24 to 48 hours.", "contents": "Establishment of a viable homograft cardiac valve bank: a rapid method of determining homograft viability. A method for determining the viability of homograft valves has been developed based on sequential measurements of glucose and pH levels of the culture medium in which cardiac valves have been maintained for short periods at 37 degrees C. Viable valves, as determined by tissue culture, showed a characteristic pattern of glucose utilization and pH reduction that was absent in nonviable valves. Upon explantation of valve leaflet fragments into tissue culture, only fragments from valves that metabolized glucose produced viable fibroblast cultures. The method reported here is rapid, requires no specialized equipment, is nondestructive, and can directly determine the viability of the valve homograft within 24 to 48 hours."}
{"id": "PMID:4040", "title": "Resin hemoperfusion for acute drug intoxication.", "content": "Eight patients with drug intoxication were hemoperfused on ten occasions at a blood-flow rate of 300 ml/min with a 650gm column of Amberlite XAD-4 resin, which is a macroreticular resin with a specific adsorptive attraction for lipid-soluble organic molecules. Column clearances of glutethimide and a variety of barbiturates ranged from 207 to 300 ml/min for treatment sessions extending from 2 1/2 to ten hours. After ingestion of 75 gm of glutethimide, one patient received hemoperfusion on three successive days for nine, ten, and eight hours, respectively. She recovered after the column removed over 30 gm of drug. The patients demonstrated dramatic clinical responses with no evidence of meaningful toxic reactions. Column hemoperfusion with Amberlite XAD-4 resin was simpler and more effective than any known method of removing barbiturates and glutethimide from the blood of patients with drug overdoses.", "contents": "Resin hemoperfusion for acute drug intoxication. Eight patients with drug intoxication were hemoperfused on ten occasions at a blood-flow rate of 300 ml/min with a 650gm column of Amberlite XAD-4 resin, which is a macroreticular resin with a specific adsorptive attraction for lipid-soluble organic molecules. Column clearances of glutethimide and a variety of barbiturates ranged from 207 to 300 ml/min for treatment sessions extending from 2 1/2 to ten hours. After ingestion of 75 gm of glutethimide, one patient received hemoperfusion on three successive days for nine, ten, and eight hours, respectively. She recovered after the column removed over 30 gm of drug. The patients demonstrated dramatic clinical responses with no evidence of meaningful toxic reactions. Column hemoperfusion with Amberlite XAD-4 resin was simpler and more effective than any known method of removing barbiturates and glutethimide from the blood of patients with drug overdoses."}
{"id": "PMID:4037", "title": "Increased mucociliary transport by adrenergic stimulation.", "content": "Tracheobronchial clearance of inhaled 6mum Teflon particles (density 2 gm/cu cm) tagged with technetium 99m was studied in healthy subjects by external measurement of the radioactivity in the lungs for two hours. Clearance, salivary secretion, blood pressure, and heart rate were determined in eight subjects after double-blind, subcutaneous administration of 0.25 mg terbutaline sulfate, a beta-adrenoceptor stimulating compound and vehicle, respectively, in a crossover study. Terbutaline produced a marked increase in clearance and a slight increase in heart rate, but had no important effect on salivary secretion or blood pressure. The result indicates that the blood concentrations of catecholamines might be of importance for the regulation of the mucociliary transport rate.", "contents": "Increased mucociliary transport by adrenergic stimulation. Tracheobronchial clearance of inhaled 6mum Teflon particles (density 2 gm/cu cm) tagged with technetium 99m was studied in healthy subjects by external measurement of the radioactivity in the lungs for two hours. Clearance, salivary secretion, blood pressure, and heart rate were determined in eight subjects after double-blind, subcutaneous administration of 0.25 mg terbutaline sulfate, a beta-adrenoceptor stimulating compound and vehicle, respectively, in a crossover study. Terbutaline produced a marked increase in clearance and a slight increase in heart rate, but had no important effect on salivary secretion or blood pressure. The result indicates that the blood concentrations of catecholamines might be of importance for the regulation of the mucociliary transport rate."}
{"id": "PMID:4041", "title": "Platelet aggregation in portal cirrhosis.", "content": "Primary and secondary platelet aggregation in response to adenosine diphosphate was studied in 24 patients with portal (La\u00ebnnec) cirrhosis and compared with platelet aggregation in 14 normal subjects. In 12 patients with cirrhosis, platelet aggregation was diminished when compared to controls. Of the 12 patients with impaired aggregation, 6 had elevated levels of fibrinogen-fibrin degradation products (FDPs), 11 had thrombocytopenia, 10 had shortened euglobulin lysis times, 11 had prolonged bleeding times, 4 had hypofibrinogenemia, and all had prolonged thrombin clotting times. The data suggest that elevated levels of serum FDPs do not explain fully the impairment of platelet aggregation or the prolongation of the thrombin clotting time that was noted in patients with advanced liver disease. A possible explanation for the prolongation of the thrombin clotting time is the presence of \"altered\" plasma fibrinogen.", "contents": "Platelet aggregation in portal cirrhosis. Primary and secondary platelet aggregation in response to adenosine diphosphate was studied in 24 patients with portal (La\u00ebnnec) cirrhosis and compared with platelet aggregation in 14 normal subjects. In 12 patients with cirrhosis, platelet aggregation was diminished when compared to controls. Of the 12 patients with impaired aggregation, 6 had elevated levels of fibrinogen-fibrin degradation products (FDPs), 11 had thrombocytopenia, 10 had shortened euglobulin lysis times, 11 had prolonged bleeding times, 4 had hypofibrinogenemia, and all had prolonged thrombin clotting times. The data suggest that elevated levels of serum FDPs do not explain fully the impairment of platelet aggregation or the prolongation of the thrombin clotting time that was noted in patients with advanced liver disease. A possible explanation for the prolongation of the thrombin clotting time is the presence of \"altered\" plasma fibrinogen."}
{"id": "PMID:4038", "title": "Study of guinea pigs fed Swiss chard grown on municipal sludge-amended soil. Multi-element content of tissues.", "content": "Swiss chard, field-grown on soil amended with 100 dry tons per acre of municipal sewage sludge from Washington, DC, was fed to guinea pigs for 28 days. Control animals were fed Swiss chard grown on unfortified soi. Forty-one elements were determined in the sludge, the plant material, and liver, kidney, muscle, adrenal, and spleen tissues by neutron activation and other methods. Elevated concentrations of several elements found in the Swiss chard grown on the sludge-soil mixture also appeared at higher levels in certain of the animal tissues. These included antimony in adrenal, cadmium in kidney, manganese in liver tissues, and tin in several tissues. The animals showed no observable toxicological effects.", "contents": "Study of guinea pigs fed Swiss chard grown on municipal sludge-amended soil. Multi-element content of tissues. Swiss chard, field-grown on soil amended with 100 dry tons per acre of municipal sewage sludge from Washington, DC, was fed to guinea pigs for 28 days. Control animals were fed Swiss chard grown on unfortified soi. Forty-one elements were determined in the sludge, the plant material, and liver, kidney, muscle, adrenal, and spleen tissues by neutron activation and other methods. Elevated concentrations of several elements found in the Swiss chard grown on the sludge-soil mixture also appeared at higher levels in certain of the animal tissues. These included antimony in adrenal, cadmium in kidney, manganese in liver tissues, and tin in several tissues. The animals showed no observable toxicological effects."}
{"id": "PMID:4042", "title": "[Counter-immunoelectrophoresis in the diagnosis of meningoencephalitis by Diplococcus pneumoniae and Hemophilus influenzae].", "content": "The presence of antigen of D. pneumoniae and H. influenzae was detected by counter-immunoelectrophoresis (CIE) in 113 LCR of children with central nervous system (CNS) infection (17 viral, 70 bacterial and 6 tuberculous). From 41 normal children spinal fluid was obtained and used as control. Precipitation band was not observed in normal children cases of viral and tuberculosis meningitis. In 21 cases of bacterial meningitis, D. pneumoniae and H. influenzae was isolated in six cases each. In six cases of bacterial meningitis were positive both bacteriological study and CIE. In 49 cases in which culture was negative only 13 gave positive CIE. When other strains of bacteria were isolated, no positive band was detected with CIE. This technic was regarded as useful for detecting etiologic agent in purulent meningitis.", "contents": "[Counter-immunoelectrophoresis in the diagnosis of meningoencephalitis by Diplococcus pneumoniae and Hemophilus influenzae]. The presence of antigen of D. pneumoniae and H. influenzae was detected by counter-immunoelectrophoresis (CIE) in 113 LCR of children with central nervous system (CNS) infection (17 viral, 70 bacterial and 6 tuberculous). From 41 normal children spinal fluid was obtained and used as control. Precipitation band was not observed in normal children cases of viral and tuberculosis meningitis. In 21 cases of bacterial meningitis, D. pneumoniae and H. influenzae was isolated in six cases each. In six cases of bacterial meningitis were positive both bacteriological study and CIE. In 49 cases in which culture was negative only 13 gave positive CIE. When other strains of bacteria were isolated, no positive band was detected with CIE. This technic was regarded as useful for detecting etiologic agent in purulent meningitis."}
{"id": "PMID:4043", "title": "Alanine dehydrogenase of the N2-fixing blue-green alga, Anabaena cylindrica.", "content": "The L-alanine dehydrogenase (ADH) of Anabaena cylindrica has been purified 700-fold. It has a molecular weight of approximately 270,000, has 6 sub-units, each of molecular weight approximately 43,000, and shows activity both in the aminating and deaminating directions. The enzyme is NADH/NAD+ specific and oxaloacetate can partially substitute for pyruvate. The Kampp for NAD+ is 14 muM and 60 muM at low and high NAD concentrations respectively.", "contents": "Alanine dehydrogenase of the N2-fixing blue-green alga, Anabaena cylindrica. The L-alanine dehydrogenase (ADH) of Anabaena cylindrica has been purified 700-fold. It has a molecular weight of approximately 270,000, has 6 sub-units, each of molecular weight approximately 43,000, and shows activity both in the aminating and deaminating directions. The enzyme is NADH/NAD+ specific and oxaloacetate can partially substitute for pyruvate. The Kampp for NAD+ is 14 muM and 60 muM at low and high NAD concentrations respectively."}
{"id": "PMID:4044", "title": "Aromatic amino acid biosynthesis in Alcaligenes eutrophus H 16 III. Properites and regulation of anthranilate synthase.", "content": "Properties and regulation of anthranilate synthase from Alcaligenes eutrophus H 16 were investigated. Anthranilate synthase was partially purified from crude extracts by affinity chromatography on tryptophan-substituted Sepharose, and was used for kinetic measurements. During the purification procedure the enzyme was stabilized by 50 mM L-glutamine or during chromatography on DEAE- cellulose and Sephadex G-200 with 30% glucerol, respectively.", "contents": "Aromatic amino acid biosynthesis in Alcaligenes eutrophus H 16 III. Properites and regulation of anthranilate synthase. Properties and regulation of anthranilate synthase from Alcaligenes eutrophus H 16 were investigated. Anthranilate synthase was partially purified from crude extracts by affinity chromatography on tryptophan-substituted Sepharose, and was used for kinetic measurements. During the purification procedure the enzyme was stabilized by 50 mM L-glutamine or during chromatography on DEAE- cellulose and Sephadex G-200 with 30% glucerol, respectively."}
{"id": "PMID:4046", "title": "Influence of industrial toxic compounds on pregnancy. VI. Some tissue enzymes in pregnant guinea pigs exposed to the action of triethylenetetramine.", "content": "Gamma-glutamyl transpeptidase activity in kidney homogenates, aspartate and alanine aminotransferase activities in liver homogenates, and cholinesterase activity in brain homogenates were determined in nonpregnant and pregnant guinea pigs exposed to absorption through the skin of the epoxy resin triethylenetetramine. Elevated activity of gamma-glutamyl transpeptidase in the kidneys of pregnant animals, and aspartate aminotransferase in the liver of nonpregnant guinea pigs were observed.", "contents": "Influence of industrial toxic compounds on pregnancy. VI. Some tissue enzymes in pregnant guinea pigs exposed to the action of triethylenetetramine. Gamma-glutamyl transpeptidase activity in kidney homogenates, aspartate and alanine aminotransferase activities in liver homogenates, and cholinesterase activity in brain homogenates were determined in nonpregnant and pregnant guinea pigs exposed to absorption through the skin of the epoxy resin triethylenetetramine. Elevated activity of gamma-glutamyl transpeptidase in the kidneys of pregnant animals, and aspartate aminotransferase in the liver of nonpregnant guinea pigs were observed."}
{"id": "PMID:4051", "title": "[Histology and histochemistry of the seal ovaries and the age-related changes in the ovaries of the Greenland seal].", "content": "Histological and histochemical methods were used to study the ovaries of Greenland seal (Pagophoca groenlandica) from birth-time up to 30 years of age and mature females of Phoca vitulina and Erignathus barbatus. The ovary of the new-born Greenland seal has fetal medullary substance which is a provisory endocrinous gland producing not only sex hormones but also corticosteron. In other species of seals the intestinal cells of the medullary substance are the equivalent of this gland. Within 3-4 weeks after birth the reduction of the fetal medullary substance is completed, it is substituted by the connective tissue and the ovary acquires its typical structure. The rest of the fetal medullary substance is in the depth of the cortex and near the infundibulum of the ovary as lipofuscincontaining cells. When the maturation period approaches, the process of the follicle atresia regularly changes: the epithelium dies quicker, and the multiplication of intestinal cells increases. The ovaries of seals are rich in interstitial cells. Their amount cyclically changes. The cells producing steroid hormones always well hydrolize AS naphthyl-phosphates, the reaction with glycerophosphate is more variable. The connective tissue is poor in acid mucopolysaccharides, its amorphous substance in the ovary cortex is rich in protein. Senile changes of the ovary are noticed in the seal beginning from 20 years of age.", "contents": "[Histology and histochemistry of the seal ovaries and the age-related changes in the ovaries of the Greenland seal]. Histological and histochemical methods were used to study the ovaries of Greenland seal (Pagophoca groenlandica) from birth-time up to 30 years of age and mature females of Phoca vitulina and Erignathus barbatus. The ovary of the new-born Greenland seal has fetal medullary substance which is a provisory endocrinous gland producing not only sex hormones but also corticosteron. In other species of seals the intestinal cells of the medullary substance are the equivalent of this gland. Within 3-4 weeks after birth the reduction of the fetal medullary substance is completed, it is substituted by the connective tissue and the ovary acquires its typical structure. The rest of the fetal medullary substance is in the depth of the cortex and near the infundibulum of the ovary as lipofuscincontaining cells. When the maturation period approaches, the process of the follicle atresia regularly changes: the epithelium dies quicker, and the multiplication of intestinal cells increases. The ovaries of seals are rich in interstitial cells. Their amount cyclically changes. The cells producing steroid hormones always well hydrolize AS naphthyl-phosphates, the reaction with glycerophosphate is more variable. The connective tissue is poor in acid mucopolysaccharides, its amorphous substance in the ovary cortex is rich in protein. Senile changes of the ovary are noticed in the seal beginning from 20 years of age."}
{"id": "PMID:4052", "title": "[Endocrine cells of the gastric mucous membrane].", "content": "In order to obtain an additional information concerning a possible functional role of the main types of the endocrine cells (EC and ECL) on investigation of aspiration biopsy specimens taken from the middle third of the stomach in patients with ulcerative disease of the duodenum and chronic gastritis was carried out. Changes in morphology, distribution and number of the endocrine cells in pathology of the mucosa and in various acidity of the gastric juice were followed up. On the basis of the data obtained the conclusion is made that serotonin-producing (EC) cells seem to have nothing to do with the regulation of the activity of the fundal glands, whereas the enterochromaffin-like cells (ECL) influence the production of hydrochloric acid by pavement cells.", "contents": "[Endocrine cells of the gastric mucous membrane]. In order to obtain an additional information concerning a possible functional role of the main types of the endocrine cells (EC and ECL) on investigation of aspiration biopsy specimens taken from the middle third of the stomach in patients with ulcerative disease of the duodenum and chronic gastritis was carried out. Changes in morphology, distribution and number of the endocrine cells in pathology of the mucosa and in various acidity of the gastric juice were followed up. On the basis of the data obtained the conclusion is made that serotonin-producing (EC) cells seem to have nothing to do with the regulation of the activity of the fundal glands, whereas the enterochromaffin-like cells (ECL) influence the production of hydrochloric acid by pavement cells."}
{"id": "PMID:4053", "title": "Tranquilizers or anti-depressants for chronic schizophrenics: a long term study.", "content": "The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years (mean). The role of adding an anti-depressant was also studied. Following a 4 week placebo period, high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks. Statistical analyses of the various change measures revealed that patients worsened significantly on placebo, all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration. No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage.", "contents": "Tranquilizers or anti-depressants for chronic schizophrenics: a long term study. The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years (mean). The role of adding an anti-depressant was also studied. Following a 4 week placebo period, high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks. Statistical analyses of the various change measures revealed that patients worsened significantly on placebo, all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration. No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage."}
{"id": "PMID:4054", "title": "Physiological index as an aid in developing airline pilot scheduling patterns.", "content": "A multiplicative and additive formula has been developed for assisting in the development of schedules for airline pilots and flight engineers. The formula is based on freshness/tiredness data derived from aircrews on world flights. It should materially assist those who develop the schedules to avoid, where possible, finalizing those crew patterns that would impose a severe physiologic load on cockpit personnel. The objective of the application of the formula is to assure that crew members retain adequate \"physiologic reserve\" in the course of flying various segments of a pattern. This enables them to absorb the stresses of schedule delays or disruptions, as well as unforeseen operational problems and flight emergencies.", "contents": "Physiological index as an aid in developing airline pilot scheduling patterns. A multiplicative and additive formula has been developed for assisting in the development of schedules for airline pilots and flight engineers. The formula is based on freshness/tiredness data derived from aircrews on world flights. It should materially assist those who develop the schedules to avoid, where possible, finalizing those crew patterns that would impose a severe physiologic load on cockpit personnel. The objective of the application of the formula is to assure that crew members retain adequate \"physiologic reserve\" in the course of flying various segments of a pattern. This enables them to absorb the stresses of schedule delays or disruptions, as well as unforeseen operational problems and flight emergencies."}
{"id": "PMID:4057", "title": "A neutral collagenase from human gastric mucosa.", "content": "Biopsy specimens of human gastric mucosa, maintained in culture for 7 days in the absence of serum, released a collagen-degrading enzyme into the medium. The yield of active enzyme reached a maximum after 2-3 days, and viable tissue, capable of protein synthesis, was essential for its production. 2. At 25 degrees C the enzyme attacked undenatured collagen in solution, resulting in a 55% loss of specific viscosity and producing the two products TCA and TCB characteristic of neutral-collagenase action. 3. Electron microscopy of segment-long-spacing crystallites of these reaction products showed the exact cleavage locus of the collagen molecules to be between bands 43 and 44 (I-43). The larger TCA and smaller TCB products were fragments representing 77 and 23% respectively of the length of the collagen molecule. 4. Optimal enzyme activity was observed over the pH range 7.5-8.5 and a mol.wt. of approx. 38000 was derived from gel-filtration studies. 5. The enzyme was shown to be inhibited by the human serum proteins alpha2-macroglobulin and a smaller component of mol.wt. approx. 40000; alpha1-anti-trypsin was not inhibitory. 6. EDTA, 1, 10-phenanthroline, cysteine and dithiothreitol all inhibited collagenase activity. 7. The gastric enzyme has properties similar to other well characterized collagenases, but differences exist with respect to its molecular size and the site of attack on the collagen molecule.", "contents": "A neutral collagenase from human gastric mucosa. Biopsy specimens of human gastric mucosa, maintained in culture for 7 days in the absence of serum, released a collagen-degrading enzyme into the medium. The yield of active enzyme reached a maximum after 2-3 days, and viable tissue, capable of protein synthesis, was essential for its production. 2. At 25 degrees C the enzyme attacked undenatured collagen in solution, resulting in a 55% loss of specific viscosity and producing the two products TCA and TCB characteristic of neutral-collagenase action. 3. Electron microscopy of segment-long-spacing crystallites of these reaction products showed the exact cleavage locus of the collagen molecules to be between bands 43 and 44 (I-43). The larger TCA and smaller TCB products were fragments representing 77 and 23% respectively of the length of the collagen molecule. 4. Optimal enzyme activity was observed over the pH range 7.5-8.5 and a mol.wt. of approx. 38000 was derived from gel-filtration studies. 5. The enzyme was shown to be inhibited by the human serum proteins alpha2-macroglobulin and a smaller component of mol.wt. approx. 40000; alpha1-anti-trypsin was not inhibitory. 6. EDTA, 1, 10-phenanthroline, cysteine and dithiothreitol all inhibited collagenase activity. 7. The gastric enzyme has properties similar to other well characterized collagenases, but differences exist with respect to its molecular size and the site of attack on the collagen molecule."}
{"id": "PMID:4058", "title": "Adsorption of glyceraldehyde 3-phosphate dehydrogenase on condensed monolayers of phospholipid.", "content": "The adsorption of [14C] alkylated glyceraldehyde 3-phosphate dehydrogenase from rabbit muscle to condensed monolayers of phosphatidic acid was investigated under a variety of conditions. 2. The rate constant for association at 20 degrees C depended on ionic strength. At I/2=60mM the rate constant was 0.39min-1. At I/2=260mM it decreased to 0.27min-1. 3. The apparent association constant (Kass.) for adsorption at I/2=60mM was 1.06 X 10(6)M-1 and was strongly influenced by subphase changes in pH and ionic strength. Measurements of Kass. at 20 degrees and 5 degrees C gave a value for the apparent enthalpy change on adsorption of -33kJ-mol-1. Calculations of the apparent change in free energy  and apparent entropy change for the adsorption process gave values of -34kJ-mol-1 and +2J-K-1-mol-1 respectively. 4. Decreasing the amount of phosphatidic acid in the monolayer by replacement with phosphatidylcholine caused the shape of the adsorption isotherm to change from apparent hyperbolic to sigmoid. Subphase changes in pH or ionic strength did not affect the shape of the adsorption isotherm. However, adsorption of enzyme on monolayers of 100% phosphatidic acid in the presence of 1mM-CaCl2 was sigmoid in nature. 5. It is concluded that glyceraldehyde 3-phosphate dehydrogenase binds to condensed charged monolayers by multiple electrostatic interactions. At low concentrations of phosphatidic acid in the monolayer or in the presence of Ca2+, this occurs in a two-step process and depends on lateral diffusion of phosphatidic acid for strong binding to take place.", "contents": "Adsorption of glyceraldehyde 3-phosphate dehydrogenase on condensed monolayers of phospholipid. The adsorption of [14C] alkylated glyceraldehyde 3-phosphate dehydrogenase from rabbit muscle to condensed monolayers of phosphatidic acid was investigated under a variety of conditions. 2. The rate constant for association at 20 degrees C depended on ionic strength. At I/2=60mM the rate constant was 0.39min-1. At I/2=260mM it decreased to 0.27min-1. 3. The apparent association constant (Kass.) for adsorption at I/2=60mM was 1.06 X 10(6)M-1 and was strongly influenced by subphase changes in pH and ionic strength. Measurements of Kass. at 20 degrees and 5 degrees C gave a value for the apparent enthalpy change on adsorption of -33kJ-mol-1. Calculations of the apparent change in free energy  and apparent entropy change for the adsorption process gave values of -34kJ-mol-1 and +2J-K-1-mol-1 respectively. 4. Decreasing the amount of phosphatidic acid in the monolayer by replacement with phosphatidylcholine caused the shape of the adsorption isotherm to change from apparent hyperbolic to sigmoid. Subphase changes in pH or ionic strength did not affect the shape of the adsorption isotherm. However, adsorption of enzyme on monolayers of 100% phosphatidic acid in the presence of 1mM-CaCl2 was sigmoid in nature. 5. It is concluded that glyceraldehyde 3-phosphate dehydrogenase binds to condensed charged monolayers by multiple electrostatic interactions. At low concentrations of phosphatidic acid in the monolayer or in the presence of Ca2+, this occurs in a two-step process and depends on lateral diffusion of phosphatidic acid for strong binding to take place."}
{"id": "PMID:4055", "title": "Blood pH and PaCO2 as chemical factors in myocardial blood flow control.", "content": "The effect of metabolic and hypercapnic acidosis on myocardial blood flow was studied during intravenous infusions of hydrochloric acid solutions (n = 12) and during passive ventilation with 5% CO2 (n = 5) in anaesthetized, closed chest dogs. Below a pH of 7.2 metabolic acidosis at normal arterial CO2-tensions caused an increase of coronary blood flow and a decrease of coronary vascular resistance associated with a narrowed myocardial arteriovenous O2-difference, indicating vasodilation at unchanged myocardial oxygen consumption. In propranolol-pretreated dogs myocardial blood flow and coronary oxygen AV difference remained unaffected, suggesting that the coronary dilatory effect of metabolic acidemia involves beta adrenergic stimulation. Coronary vasodilation induced by increasing arterial pCO2 was found to the significantly greater as compared with the dilatory effect of metabolic acidosis at the same blood pH level. Blocking of beta receptors did not reduce the coronary response to increased arterial CO2-tensions. It is concluded that the coronary vasodilation observed during hypercapnic acidosis is neither mediated by a beta adrenergic stimulation nor dependent of the concomitant change in blood pH. The possible sites of the coronary dilatory actions of increased arterial CO2-tensions are discussed.", "contents": "Blood pH and PaCO2 as chemical factors in myocardial blood flow control. The effect of metabolic and hypercapnic acidosis on myocardial blood flow was studied during intravenous infusions of hydrochloric acid solutions (n = 12) and during passive ventilation with 5% CO2 (n = 5) in anaesthetized, closed chest dogs. Below a pH of 7.2 metabolic acidosis at normal arterial CO2-tensions caused an increase of coronary blood flow and a decrease of coronary vascular resistance associated with a narrowed myocardial arteriovenous O2-difference, indicating vasodilation at unchanged myocardial oxygen consumption. In propranolol-pretreated dogs myocardial blood flow and coronary oxygen AV difference remained unaffected, suggesting that the coronary dilatory effect of metabolic acidemia involves beta adrenergic stimulation. Coronary vasodilation induced by increasing arterial pCO2 was found to the significantly greater as compared with the dilatory effect of metabolic acidosis at the same blood pH level. Blocking of beta receptors did not reduce the coronary response to increased arterial CO2-tensions. It is concluded that the coronary vasodilation observed during hypercapnic acidosis is neither mediated by a beta adrenergic stimulation nor dependent of the concomitant change in blood pH. The possible sites of the coronary dilatory actions of increased arterial CO2-tensions are discussed."}
{"id": "PMID:4059", "title": "Enzymic hydrolysis of acetylcarnitine in liver from rats, sheep and cows.", "content": "1. The enzymic utilization of O-acetyl-l-carnitine other than via carnitine acetyltransferase (EC 2.3.1.7) was investigated in liver homogenates from rats, sheep and dry cows. 2. An enzymic utilization of O-acetyl-l-carnitine via hydrolysis of the ester bond to yield stoicheiometric quantities of acetate and l-carnitine was demonstrated; 0.55, 0.53 and 0.30mumol of acetyl-l-carnitine were utilized/min per g fresh wt. of liver homogenates from rats, sheep and dry cows respectively. 3. The acetylcarnitine hydrolysis activity was not due to a non-specific esterase or non-specific cholinesterase. O-Acetyl-d-carnitine was not utilized. 4. The activity was associated with the enriched outer mitochondrial membrane fraction from rat liver. Isolation of this fraction resulted in an eightfold purification of acetylcarnitine hydrolase activity. 4. The K(m) for this acetylcarnitine utilization was 2mm and 1.5mm for rat and sheep liver homogenates respectively. 6. There was a significant increase in acetylcarnitine hydrolase in rats on starvation and cows on lactation and a significant decrease in sheep that were severely alloxan-diabetic. 7. The physiological role of an acetylcarnitine hydrolase is discussed in relation to coupling with carnitine acetyltransferase for the relief of ;acetyl pressure'.", "contents": "Enzymic hydrolysis of acetylcarnitine in liver from rats, sheep and cows. 1. The enzymic utilization of O-acetyl-l-carnitine other than via carnitine acetyltransferase (EC 2.3.1.7) was investigated in liver homogenates from rats, sheep and dry cows. 2. An enzymic utilization of O-acetyl-l-carnitine via hydrolysis of the ester bond to yield stoicheiometric quantities of acetate and l-carnitine was demonstrated; 0.55, 0.53 and 0.30mumol of acetyl-l-carnitine were utilized/min per g fresh wt. of liver homogenates from rats, sheep and dry cows respectively. 3. The acetylcarnitine hydrolysis activity was not due to a non-specific esterase or non-specific cholinesterase. O-Acetyl-d-carnitine was not utilized. 4. The activity was associated with the enriched outer mitochondrial membrane fraction from rat liver. Isolation of this fraction resulted in an eightfold purification of acetylcarnitine hydrolase activity. 4. The K(m) for this acetylcarnitine utilization was 2mm and 1.5mm for rat and sheep liver homogenates respectively. 6. There was a significant increase in acetylcarnitine hydrolase in rats on starvation and cows on lactation and a significant decrease in sheep that were severely alloxan-diabetic. 7. The physiological role of an acetylcarnitine hydrolase is discussed in relation to coupling with carnitine acetyltransferase for the relief of ;acetyl pressure'."}
{"id": "PMID:4060", "title": "Creatine kinase equilibrium and lactate content compared with muscle pH in tissue samples obtained after isometric exercise.", "content": "Muscle biopsies taken from the musculus quadriceps femoris of man were analysed for pH, ATP, ADP, AMP, creatine phosphate, creatine, lactate and pyruvate. Biopsies were taken at rest, after circulatory occlusion and after isometric contraction. Muscle pH decreased from 7.09 at rest to 6.56 after isometric exercise to fatigue. Decrease in muscle pH was linearly related to accumulation of lactate plus pyruvate. An increase of 22mumol of lactate plus pyruvate per g of muscle resulted in a fall of 0.5pH unit. The apparent equilibrium constant of the creatine kinase reaction (apparent K(CK)) increased after isometric contraction and a linear relationship between log(apparent K(CK)) and muscle pH was obtained. The low content of creatine phosphate in muscle after contraction as analysed from needle-biopsy samples is believed to be a consequence of an altered equilibrium state of the creatine kinase reaction. This in turn is attributed mainly to a change in intracellular pH.", "contents": "Creatine kinase equilibrium and lactate content compared with muscle pH in tissue samples obtained after isometric exercise. Muscle biopsies taken from the musculus quadriceps femoris of man were analysed for pH, ATP, ADP, AMP, creatine phosphate, creatine, lactate and pyruvate. Biopsies were taken at rest, after circulatory occlusion and after isometric contraction. Muscle pH decreased from 7.09 at rest to 6.56 after isometric exercise to fatigue. Decrease in muscle pH was linearly related to accumulation of lactate plus pyruvate. An increase of 22mumol of lactate plus pyruvate per g of muscle resulted in a fall of 0.5pH unit. The apparent equilibrium constant of the creatine kinase reaction (apparent K(CK)) increased after isometric contraction and a linear relationship between log(apparent K(CK)) and muscle pH was obtained. The low content of creatine phosphate in muscle after contraction as analysed from needle-biopsy samples is believed to be a consequence of an altered equilibrium state of the creatine kinase reaction. This in turn is attributed mainly to a change in intracellular pH."}
{"id": "PMID:4061", "title": "The microbial metabolism of acetophenone. Metabolism of acetophenone and some chloroacetophenones by an Arthrobacter species.", "content": "1. An organism that utilizes acetophenone as sole source of carbon and energy was isolated in pure culture and tentatively identified as an Arthrobacter sp. 2. Cell-free extracts of the acetophenone-grown organism contained an enzyme, acetophenone oxygenase, that catalysed an NADPH-dependent consumption of O(2) in the presence of the growth substrate; approx. 1mol of O(2) and 1mol of NADPH were consumed per mol of acetophenone oxidized. 3. Cell-free extracts also contained an enzyme capable of the hydrolysis of phenyl acetate to phenol and acetate. The amount of this esterase was increased markedly by growth on acetophenone. 4. The observed products of the acetophenone oxygenase reaction by crude cell-free extracts were phenol and acetate. However, inhibition of the phenyl acetate esterase by paraoxon resulted in the formation of phenyl acetate from acetophenone. 5. A degradative sequence is proposed in which acetophenone is metabolized by an oxygen-insertion reaction to form phenyl acetate. Further metabolism occurs by hydrolysis of this ester. 6. The organism and extracts were shown to metabolize chlorinated acetophenones. The environmental implications of this observation are discussed.", "contents": "The microbial metabolism of acetophenone. Metabolism of acetophenone and some chloroacetophenones by an Arthrobacter species. 1. An organism that utilizes acetophenone as sole source of carbon and energy was isolated in pure culture and tentatively identified as an Arthrobacter sp. 2. Cell-free extracts of the acetophenone-grown organism contained an enzyme, acetophenone oxygenase, that catalysed an NADPH-dependent consumption of O(2) in the presence of the growth substrate; approx. 1mol of O(2) and 1mol of NADPH were consumed per mol of acetophenone oxidized. 3. Cell-free extracts also contained an enzyme capable of the hydrolysis of phenyl acetate to phenol and acetate. The amount of this esterase was increased markedly by growth on acetophenone. 4. The observed products of the acetophenone oxygenase reaction by crude cell-free extracts were phenol and acetate. However, inhibition of the phenyl acetate esterase by paraoxon resulted in the formation of phenyl acetate from acetophenone. 5. A degradative sequence is proposed in which acetophenone is metabolized by an oxygen-insertion reaction to form phenyl acetate. Further metabolism occurs by hydrolysis of this ester. 6. The organism and extracts were shown to metabolize chlorinated acetophenones. The environmental implications of this observation are discussed."}
{"id": "PMID:4062", "title": "Permeability to calcium of pigeon erythrocyte 'ghosts' studied by using the calcium-activated luminescent protein, obelin.", "content": "1. Obelin, the Ca(2+)-activated luminescent protein from the hydroid Obelia geniculata, was sealed inside pigeon erythrocyte ;ghosts' in order to investigate effects on their permeability of different methods of preparation and of the bivalent cation ionophore A23187. 2. Changes in free Ca(2+) within the ;ghosts' were studied by following the rate of luminescence of obelin. The possibility that the obelin might have been released from the ;ghosts' during an experiment was investigated by studying the release of inulin and pyruvate kinase from the ;ghosts'. Less than 10% of the inulin or pyruvate kinase sealed within the ;ghosts' was released under any of the experimental conditions. 3. Triton X-100 (0.1-10%, v/v) made the ;ghosts' highly permeable to Ca(2+). In the presence of 1mm-Ca(2+) and Triton, 95-100% of the obelin was utilized within 10-20s. 4. A time-course of resealing ;ghosts' at 37 degrees C showed that over a period of 90min, the ;ghosts' became gradually less permeable to Ca(2+). ;Ghosts' which remained at 0 degrees C retained only a small concentration of obelin and ATP, and were highly permeable to Ca(2+). 5. Erythrocyte ;ghosts' resealed for 30min at 20 degrees C rather than 37 degrees C were more permeable to Ca(2+), as shown by the fact that 92% of the obelin in the ;ghosts' was utilized during the first 60s after the addition of 1mm-Ca(2+), as opposed to 44% for ;ghosts' resealed at 37 degrees C. 6. Haemolysis at pH6.0 rather than 7.0 resulted in ;ghosts' which were highly permeable to Ca(2+) after resealing for 60min at 37 degrees C. Of the obelin in the ;ghosts', produced by haemolysis at pH6.0, 90% was utilized in the first 60s after the addition of 1mm-Ca(2+) compared with 23% for ;ghosts' produced at pH7.0. 7. The bivalent cation ionophore A23187 increased the permeability of the ;ghosts' to Ca(2+). Maximum effects of the ionophore (16mug/ml) were obtained by preincubating the ;ghosts' with the ionophore A23187 (16mug/ml) in the presence of a low concentration of Mg(2+) and in the absence of Ca(2+).", "contents": "Permeability to calcium of pigeon erythrocyte 'ghosts' studied by using the calcium-activated luminescent protein, obelin. 1. Obelin, the Ca(2+)-activated luminescent protein from the hydroid Obelia geniculata, was sealed inside pigeon erythrocyte ;ghosts' in order to investigate effects on their permeability of different methods of preparation and of the bivalent cation ionophore A23187. 2. Changes in free Ca(2+) within the ;ghosts' were studied by following the rate of luminescence of obelin. The possibility that the obelin might have been released from the ;ghosts' during an experiment was investigated by studying the release of inulin and pyruvate kinase from the ;ghosts'. Less than 10% of the inulin or pyruvate kinase sealed within the ;ghosts' was released under any of the experimental conditions. 3. Triton X-100 (0.1-10%, v/v) made the ;ghosts' highly permeable to Ca(2+). In the presence of 1mm-Ca(2+) and Triton, 95-100% of the obelin was utilized within 10-20s. 4. A time-course of resealing ;ghosts' at 37 degrees C showed that over a period of 90min, the ;ghosts' became gradually less permeable to Ca(2+). ;Ghosts' which remained at 0 degrees C retained only a small concentration of obelin and ATP, and were highly permeable to Ca(2+). 5. Erythrocyte ;ghosts' resealed for 30min at 20 degrees C rather than 37 degrees C were more permeable to Ca(2+), as shown by the fact that 92% of the obelin in the ;ghosts' was utilized during the first 60s after the addition of 1mm-Ca(2+), as opposed to 44% for ;ghosts' resealed at 37 degrees C. 6. Haemolysis at pH6.0 rather than 7.0 resulted in ;ghosts' which were highly permeable to Ca(2+) after resealing for 60min at 37 degrees C. Of the obelin in the ;ghosts', produced by haemolysis at pH6.0, 90% was utilized in the first 60s after the addition of 1mm-Ca(2+) compared with 23% for ;ghosts' produced at pH7.0. 7. The bivalent cation ionophore A23187 increased the permeability of the ;ghosts' to Ca(2+). Maximum effects of the ionophore (16mug/ml) were obtained by preincubating the ;ghosts' with the ionophore A23187 (16mug/ml) in the presence of a low concentration of Mg(2+) and in the absence of Ca(2+)."}
{"id": "PMID:4063", "title": "The action of tributyltin on energy coupling in coupling-factor-deficient submitochondrial particles.", "content": "1. Tributyltin at concentrations of approx. 1nmol/mg of protein induces respiratory control and lessens the protein permeability of coupling-factor-deficient submitochondrial particles. 2. At these concentrations or lower, it increases the P/O ratio of the particles to a small extent and inhibits the adenosine triphosphatase activity without greatly increasing its sensitivity to uncoupling agents. 3. It fails to stimulate ATP-driven reversed electron transport or transhydrogenase, but stimulates the transhydrogenase driven by aerobic succinate oxidation. 4. The results indicate that, unlike oligomycin, tributyltin does not discriminate between damaged and intact ATP-synthesizing complexes. 5. The relationship between the oligomycin- and tributyltin-binding sites is discussed.", "contents": "The action of tributyltin on energy coupling in coupling-factor-deficient submitochondrial particles. 1. Tributyltin at concentrations of approx. 1nmol/mg of protein induces respiratory control and lessens the protein permeability of coupling-factor-deficient submitochondrial particles. 2. At these concentrations or lower, it increases the P/O ratio of the particles to a small extent and inhibits the adenosine triphosphatase activity without greatly increasing its sensitivity to uncoupling agents. 3. It fails to stimulate ATP-driven reversed electron transport or transhydrogenase, but stimulates the transhydrogenase driven by aerobic succinate oxidation. 4. The results indicate that, unlike oligomycin, tributyltin does not discriminate between damaged and intact ATP-synthesizing complexes. 5. The relationship between the oligomycin- and tributyltin-binding sites is discussed."}
{"id": "PMID:4080", "title": "Effects of the cardioselective beta-adrenergic receptor blocking agent metoprolol in angina pectoris. Subacute study with exercise tests.", "content": "The effect of a cardioselective beta-adrenergic blocking agent, metoprolol, on symptoms and exercise tolerance was studied in 16 patients with angina pectoris. Metroprolol was compared with placebo at two dose levels (20 mg t.d.s. and 50 mg t.d.s.) in a double-blind trial in 14 patients. Compared with placebo, metroprolol caused a significant reduction of heart rate and systolic blood pressure during exercise, and consequently a reduction of the rate-pressure product. The reduction was greater with 50 mg t.d.s. than with 20 mg t.d.s. The exercise tolerance measured as total work increased significantly by 21 per cent during treatment with metroprolol 20 mg t.d.s., and by 17 per cent during treatment with 50 mg t.d.s. There was a reduction in the number of anginal attacks and in nitroglycerin consumption, and subjective improvement of angina pectoris at both dose levels of metroprolol. No signs of cardiac failure appeared during any of the four treatment periods. Heart volume showed no significant change. Unwanted effects were of the same frequency and severity during treatment with metroprolol at both dose levels as with placebo.", "contents": "Effects of the cardioselective beta-adrenergic receptor blocking agent metoprolol in angina pectoris. Subacute study with exercise tests. The effect of a cardioselective beta-adrenergic blocking agent, metoprolol, on symptoms and exercise tolerance was studied in 16 patients with angina pectoris. Metroprolol was compared with placebo at two dose levels (20 mg t.d.s. and 50 mg t.d.s.) in a double-blind trial in 14 patients. Compared with placebo, metroprolol caused a significant reduction of heart rate and systolic blood pressure during exercise, and consequently a reduction of the rate-pressure product. The reduction was greater with 50 mg t.d.s. than with 20 mg t.d.s. The exercise tolerance measured as total work increased significantly by 21 per cent during treatment with metroprolol 20 mg t.d.s., and by 17 per cent during treatment with 50 mg t.d.s. There was a reduction in the number of anginal attacks and in nitroglycerin consumption, and subjective improvement of angina pectoris at both dose levels of metroprolol. No signs of cardiac failure appeared during any of the four treatment periods. Heart volume showed no significant change. Unwanted effects were of the same frequency and severity during treatment with metroprolol at both dose levels as with placebo."}
{"id": "PMID:4083", "title": "The availability of folates in man: effect of orange juice supplement on intestinal conjugase.", "content": "The mechanisms of the low availability of endogenous folates in orange juice and the inhibitory effects on the availability of pteroylheptaglutamate (PteGlu7) caused by orange juice supplements were investigated in man by the use of simulated orange juice (containing the principal components: citric acid, malic acid, etc.) with several different pHs. The endogenous folates in orange juice were identified as mainly 5-methyl reduced derivatives of pteroylpolyglutamates (40-45% pentaglutamate, 10-15% tetraglutamate, 30-40% monoglutamate, and the rest were tri-and diglutamates). The availability of PteGlu7 is decreased to 54% by supplementation with 600 g concentrated orange juice (pH 3.7) and to 39% and 66% by the supplement of 24 g and 12 g citric acid (pH 3.7), respectively. Neutralization of 12 g citric acid to pH 6.4 largely reverses the inhibitory effect. On the other hand, the availability of pteroylmonoglutamate (PteGlu) is not influenced by a supplement of orange juice or citric acid. The results suggest that the low availability of PteGlu7 is due to the inhibition of intestinal conjugase caused by the low pH. These observations suggest that pH of foodstuffs may be an important factor in the absorption of polyglutamate forms of folate.", "contents": "The availability of folates in man: effect of orange juice supplement on intestinal conjugase. The mechanisms of the low availability of endogenous folates in orange juice and the inhibitory effects on the availability of pteroylheptaglutamate (PteGlu7) caused by orange juice supplements were investigated in man by the use of simulated orange juice (containing the principal components: citric acid, malic acid, etc.) with several different pHs. The endogenous folates in orange juice were identified as mainly 5-methyl reduced derivatives of pteroylpolyglutamates (40-45% pentaglutamate, 10-15% tetraglutamate, 30-40% monoglutamate, and the rest were tri-and diglutamates). The availability of PteGlu7 is decreased to 54% by supplementation with 600 g concentrated orange juice (pH 3.7) and to 39% and 66% by the supplement of 24 g and 12 g citric acid (pH 3.7), respectively. Neutralization of 12 g citric acid to pH 6.4 largely reverses the inhibitory effect. On the other hand, the availability of pteroylmonoglutamate (PteGlu) is not influenced by a supplement of orange juice or citric acid. The results suggest that the low availability of PteGlu7 is due to the inhibition of intestinal conjugase caused by the low pH. These observations suggest that pH of foodstuffs may be an important factor in the absorption of polyglutamate forms of folate."}
{"id": "PMID:4084", "title": "The use of a single venous blood sample to assess oxygen binding in haemoglobin.", "content": "The measurement of pH, PO2, PCO2 and SO2 in a single venous blood sample can be used to determine the P50 at standard or at in vivo conditions. This technique makes it feasible for a physician, firstly, to make an assessment of the net adaptation of the red cell to reductions in blood oxygen content or flow and, secondly, to make an initial assessment of whether a haemoglobin with altered affinity for oxygen is present in subjects with polycythaemia or anaemia.", "contents": "The use of a single venous blood sample to assess oxygen binding in haemoglobin. The measurement of pH, PO2, PCO2 and SO2 in a single venous blood sample can be used to determine the P50 at standard or at in vivo conditions. This technique makes it feasible for a physician, firstly, to make an assessment of the net adaptation of the red cell to reductions in blood oxygen content or flow and, secondly, to make an initial assessment of whether a haemoglobin with altered affinity for oxygen is present in subjects with polycythaemia or anaemia."}
{"id": "PMID:4085", "title": "The state of energization of the membrane of Escherichia coli as affected by physiological conditions and colicin K.", "content": "The bacterial protein colicin K, when added to sensitive Escherichia coli in the presence of 3,3'-dihexyloxacarbocyanine, cuases a doubling in fluorescence of the probe. Glucose and oxygen cause a decreased fluorescence while anoxia and cyanide cause a rise in fluorescence. These results in conjunction with the work of other laboratories suggest that colicin K causes a depolarization of the transmembrane electrical potential. Fluorescence in the absence of colicin K was relatively independent of KCl, NaCl, and MgCl2 concentrations below 0.1 M. Although colicin K caused rapid efflux of the K+ analogue 86Rb+, the fluorescence rise was only partially blocked by 0.13 M KCl. The level of fluorescence caused by the action of colcin K was inversely proportional to the logarithm of the concentration of MgCl2 over the range of 2 muM to 4 mM. This suggests that a Nernst electrochemical potential for an anion can counteract a membrane depolarization caused by colcin. After colcin K action, the fluorescence of the carbocyanine could be further increased by anoxia or cyanide. The distribution of the weak base dimethyloxazolidinedione indicated that the pH in the interior of aerobic E. coli supplied with lactate was alkaline by 0.1 unit and unaffected by colicin. These results suggest that colicin K does not completely depolarize the membrane potential and does not interfere with the component of membrane energization generated by electron transport. Colicin K does not act as a cationophore. The partial depolarization of the membrane may account for the inhibition of active solute transport caused by colicin K.", "contents": "The state of energization of the membrane of Escherichia coli as affected by physiological conditions and colicin K. The bacterial protein colicin K, when added to sensitive Escherichia coli in the presence of 3,3'-dihexyloxacarbocyanine, cuases a doubling in fluorescence of the probe. Glucose and oxygen cause a decreased fluorescence while anoxia and cyanide cause a rise in fluorescence. These results in conjunction with the work of other laboratories suggest that colicin K causes a depolarization of the transmembrane electrical potential. Fluorescence in the absence of colicin K was relatively independent of KCl, NaCl, and MgCl2 concentrations below 0.1 M. Although colicin K caused rapid efflux of the K+ analogue 86Rb+, the fluorescence rise was only partially blocked by 0.13 M KCl. The level of fluorescence caused by the action of colcin K was inversely proportional to the logarithm of the concentration of MgCl2 over the range of 2 muM to 4 mM. This suggests that a Nernst electrochemical potential for an anion can counteract a membrane depolarization caused by colcin. After colcin K action, the fluorescence of the carbocyanine could be further increased by anoxia or cyanide. The distribution of the weak base dimethyloxazolidinedione indicated that the pH in the interior of aerobic E. coli supplied with lactate was alkaline by 0.1 unit and unaffected by colicin. These results suggest that colicin K does not completely depolarize the membrane potential and does not interfere with the component of membrane energization generated by electron transport. Colicin K does not act as a cationophore. The partial depolarization of the membrane may account for the inhibition of active solute transport caused by colicin K."}
{"id": "PMID:4086", "title": "The acid-catalyzed decompostion of phenacylcobalamin: evidence for the formation of an enol-Co(III) pi-complex intermediate.", "content": "Phenacylcobalamin has been synthesized and characterized by thin-layer chromatography and uv-visible spectroscopy, as well as identification of the cobalt-containing and organic products of its cleavage in acid and base and by aerobic photolysis. The major organic product from all three cleavage reactions is acetophenone and the cobalt-containing product is aquacobalamin (or hydroxocobalamin, its conjugate base). In aqueous acidic solution (pH 0 to 7.3, ionic strength 1.0 M, and 25.0 degrees C), the kinetics of the formation of aquacobalamin are biphasic representing the linear sum of two exponential terms. The pH dependence of the first-order rate constant of both phases shows a first-order dependence on proton concentration but with an inflection point ot pH 3.55 for the faster phase and at pH 4.03 for the slower phase. This behavior is interpreted in terms of the specific acid catalyzed formation of an intermediate from both \"base on\" and \"base off\" phenacylcobalamin with different second-order rate constants for each form, followed by an intermediate decompotion step with a similar formal mechanism. The nature of the intermediate is discussed and it is concluded to be a pi-complex between cob(III)alamin and the enol of acetophenone.", "contents": "The acid-catalyzed decompostion of phenacylcobalamin: evidence for the formation of an enol-Co(III) pi-complex intermediate. Phenacylcobalamin has been synthesized and characterized by thin-layer chromatography and uv-visible spectroscopy, as well as identification of the cobalt-containing and organic products of its cleavage in acid and base and by aerobic photolysis. The major organic product from all three cleavage reactions is acetophenone and the cobalt-containing product is aquacobalamin (or hydroxocobalamin, its conjugate base). In aqueous acidic solution (pH 0 to 7.3, ionic strength 1.0 M, and 25.0 degrees C), the kinetics of the formation of aquacobalamin are biphasic representing the linear sum of two exponential terms. The pH dependence of the first-order rate constant of both phases shows a first-order dependence on proton concentration but with an inflection point ot pH 3.55 for the faster phase and at pH 4.03 for the slower phase. This behavior is interpreted in terms of the specific acid catalyzed formation of an intermediate from both \"base on\" and \"base off\" phenacylcobalamin with different second-order rate constants for each form, followed by an intermediate decompotion step with a similar formal mechanism. The nature of the intermediate is discussed and it is concluded to be a pi-complex between cob(III)alamin and the enol of acetophenone."}
{"id": "PMID:4087", "title": "A quantitative treatment of the kinetics of the folding transition of ribonuclease A.", "content": "New experimental data and a quantitative theoretical treatment are given for the kinetics of the thermal folding transition of ribonuclease A at pH 3.0. A three-species mechanism is used as a starting point for the analysis: U1 (slow) in equilibrium U2(fast) in equilibrium N, where U1 and U2 are two forms of the unfolded enzyme with markedly different rates of refolding and N is the native enzyme. This mechanism is based on certain facts established in previous studies of refolding. The kinetics of unfolding and refolding show two phases a fast phase and a slow phase, over a range of temperatures extending above the transition midpoint, Tm. The three-species mechanism can be used in this range. At higher temperatures a new much faster kinetic phase is also observed corresponding to the transient formation of a new intermediate (I). Although the general solution for a four-species mechanism is complex it is not difficult to extend the three-species analysis for the special case found here, in which the fast reaction (I in equilibrium N) is well separated from the other two reactions. At temperatures below the transition zone the slow phase of refolding becomes kinetically complex. No attempt has been made to extend the analysis to include this effect. The basic test of the three-state analysis is the prediction as a function of temperature of alpha2, the relative amplitude of the fast phase, both for unfolding and refolding. At temperatures above Tm for which the three-state analysis must be extended to include the new intermediate I, a crresponding quanitity alpha2(cor) is predicted and compared with measured values. Data used in the three-state prediction are values of tau2 and tau1, the time constants of the fast and slow kinetic phases, plus a single value of alpha2 measured when tau2 and tau1 are well separated. The observed and predicted values of alpha2 agree within experimental error. The analysis predicts correctly that, for these experiments, alpha2 should have the same value in unfolding as in refolding in the final conditions. The analysis also predicts satisfactorily the equilibrium transition curve from kinetic data alone. Four striking properties of the kinetics are  explained or correlated by the analysis: (a) the drop in alpha2 to a minimum near Tm as well as the delayed rise in alpha2 above Tm;(b) the vanishing of alpha1 above the transition zone; (c) the sharp drop in tau1 inside the transition zone followed by a partial leveling off outside this zone; and (d) the passage of tau2 through a maximum near Tm. Through a comparison of observed and predicted values of alpha2, the analysis also rules out the alternative three-species mechanism U1 (slow) in equilibrium N (fast) in equilibrium U2. Finally, the temperature dependence of the amplitude for the fast reaction (I in equilibrium N) is discussed; the behavior of I is like that of U2 and I may be an unfolded species populated at equilibrium...", "contents": "A quantitative treatment of the kinetics of the folding transition of ribonuclease A. New experimental data and a quantitative theoretical treatment are given for the kinetics of the thermal folding transition of ribonuclease A at pH 3.0. A three-species mechanism is used as a starting point for the analysis: U1 (slow) in equilibrium U2(fast) in equilibrium N, where U1 and U2 are two forms of the unfolded enzyme with markedly different rates of refolding and N is the native enzyme. This mechanism is based on certain facts established in previous studies of refolding. The kinetics of unfolding and refolding show two phases a fast phase and a slow phase, over a range of temperatures extending above the transition midpoint, Tm. The three-species mechanism can be used in this range. At higher temperatures a new much faster kinetic phase is also observed corresponding to the transient formation of a new intermediate (I). Although the general solution for a four-species mechanism is complex it is not difficult to extend the three-species analysis for the special case found here, in which the fast reaction (I in equilibrium N) is well separated from the other two reactions. At temperatures below the transition zone the slow phase of refolding becomes kinetically complex. No attempt has been made to extend the analysis to include this effect. The basic test of the three-state analysis is the prediction as a function of temperature of alpha2, the relative amplitude of the fast phase, both for unfolding and refolding. At temperatures above Tm for which the three-state analysis must be extended to include the new intermediate I, a crresponding quanitity alpha2(cor) is predicted and compared with measured values. Data used in the three-state prediction are values of tau2 and tau1, the time constants of the fast and slow kinetic phases, plus a single value of alpha2 measured when tau2 and tau1 are well separated. The observed and predicted values of alpha2 agree within experimental error. The analysis predicts correctly that, for these experiments, alpha2 should have the same value in unfolding as in refolding in the final conditions. The analysis also predicts satisfactorily the equilibrium transition curve from kinetic data alone. Four striking properties of the kinetics are  explained or correlated by the analysis: (a) the drop in alpha2 to a minimum near Tm as well as the delayed rise in alpha2 above Tm;(b) the vanishing of alpha1 above the transition zone; (c) the sharp drop in tau1 inside the transition zone followed by a partial leveling off outside this zone; and (d) the passage of tau2 through a maximum near Tm. Through a comparison of observed and predicted values of alpha2, the analysis also rules out the alternative three-species mechanism U1 (slow) in equilibrium N (fast) in equilibrium U2. Finally, the temperature dependence of the amplitude for the fast reaction (I in equilibrium N) is discussed; the behavior of I is like that of U2 and I may be an unfolded species populated at equilibrium..."}
{"id": "PMID:4088", "title": "Rate enhancement specificity with alpha-chymotrypsin: temperature dependence of deacylation.", "content": "The relative rate of the hydrolysis of 2-(5-n-alkyl)furoyl-alpha-chymotrypsin reaches a maximum with the propyl derivative. The Arrhenius plots for the hydrolyses of the 2-furoyl-, 2-(5-ethyl)furoyl-, and 2-(5-n-propyl)furoyl-alpha-chymotrypsins display a discontinuity, while the plots obtained with the ramaining furoyl derivatives 5-methyl, 5-n-butyl, and 5-n-amyl are linear. We conclude that the deacylation of the furoyl derivatives of alpha-chymotrypsin involves a minimum of two elementary reaction steps. Depending upon the reaction conditions, rate enhancement specificity appears to be either entropy or enthalpy controlled.", "contents": "Rate enhancement specificity with alpha-chymotrypsin: temperature dependence of deacylation. The relative rate of the hydrolysis of 2-(5-n-alkyl)furoyl-alpha-chymotrypsin reaches a maximum with the propyl derivative. The Arrhenius plots for the hydrolyses of the 2-furoyl-, 2-(5-ethyl)furoyl-, and 2-(5-n-propyl)furoyl-alpha-chymotrypsins display a discontinuity, while the plots obtained with the ramaining furoyl derivatives 5-methyl, 5-n-butyl, and 5-n-amyl are linear. We conclude that the deacylation of the furoyl derivatives of alpha-chymotrypsin involves a minimum of two elementary reaction steps. Depending upon the reaction conditions, rate enhancement specificity appears to be either entropy or enthalpy controlled."}
{"id": "PMID:4089", "title": "Optimal conditions and specificity of interaction of a distinct class of nonhistone chromosomal proteins with DNA.", "content": "A subclass of nonhistone chromatin proteins with high DNA affinity has been isolated from rat liver. The interaction of the isolated proteins with DNA in vitro was characterized utilizing a nitrocellulose filter binding technique. The temperature, time, concentration, ionic strength, and pH dependence were characterized. Optimal interaction was observed at 0.19 M naCl, pH 7.5 with a protein to DNA ratio of 13 (w/w). Equilibrium and kinetic competition experiments indicated that these proteins interact optimally with A-T rich and single-stranded DNA. The data also suggest that these proteins might affect the helixcoil transiton of DNA.", "contents": "Optimal conditions and specificity of interaction of a distinct class of nonhistone chromosomal proteins with DNA. A subclass of nonhistone chromatin proteins with high DNA affinity has been isolated from rat liver. The interaction of the isolated proteins with DNA in vitro was characterized utilizing a nitrocellulose filter binding technique. The temperature, time, concentration, ionic strength, and pH dependence were characterized. Optimal interaction was observed at 0.19 M naCl, pH 7.5 with a protein to DNA ratio of 13 (w/w). Equilibrium and kinetic competition experiments indicated that these proteins interact optimally with A-T rich and single-stranded DNA. The data also suggest that these proteins might affect the helixcoil transiton of DNA."}
{"id": "PMID:4090", "title": "The subcellular distribution of adenylate and guanylate cyclases in murine lymphoid cells.", "content": "Membrane vesicles can be prepared from murine lymphoid cells by nitrogen cavitation and fractionated by sedimentation through nonlinear sucrose density gradients. Two subpopulations of membrane vesicles, PMI and PMII, can be distinguished on the basis of sedimentation rate. The subcellular distribution of adenylate and guanylate cyclases in these membrane subpopulations have been compared with the distribution of a number of marker enzymes. Approximately 20-30% of the total adenylate and guanylate cyclase activity is located at the top of the sucrose gradient (soluble enzyme), the remainder of the activity being distributed in the PMI and PMII fractions (membrane-bound enzyme). More than 90% of the 5'-nucleotidase and NADH oxidase activities detected in lymphoid cell homogenates are located in PMI and PMII fractions, whereas succinate cytochrome c reductase activity is detected only in the PMII fractions. In addition, beta-galactosidase activity is distributed in the soluble and PMII fractions of the sucrose density gradients. On the basis of the fractionation patterns of these various enzyme activities, it appears that PMI fractions contain vesicles of plasma membrane and endoplasmic reticulum, whereas PMII fractions contain mitochondria, lysomes, and plasma membrane vesicles. Approximately 30-40% of the adenylate and guanylate cyclase activities in PMII can be converted to a PMI-like form following dialysis and resedimentation through a second nonlinear sucrose gradient. Adenylate and guanulate cyclases can be distinguished on the basis of sensitivity to nonionic detergents.", "contents": "The subcellular distribution of adenylate and guanylate cyclases in murine lymphoid cells. Membrane vesicles can be prepared from murine lymphoid cells by nitrogen cavitation and fractionated by sedimentation through nonlinear sucrose density gradients. Two subpopulations of membrane vesicles, PMI and PMII, can be distinguished on the basis of sedimentation rate. The subcellular distribution of adenylate and guanylate cyclases in these membrane subpopulations have been compared with the distribution of a number of marker enzymes. Approximately 20-30% of the total adenylate and guanylate cyclase activity is located at the top of the sucrose gradient (soluble enzyme), the remainder of the activity being distributed in the PMI and PMII fractions (membrane-bound enzyme). More than 90% of the 5'-nucleotidase and NADH oxidase activities detected in lymphoid cell homogenates are located in PMI and PMII fractions, whereas succinate cytochrome c reductase activity is detected only in the PMII fractions. In addition, beta-galactosidase activity is distributed in the soluble and PMII fractions of the sucrose density gradients. On the basis of the fractionation patterns of these various enzyme activities, it appears that PMI fractions contain vesicles of plasma membrane and endoplasmic reticulum, whereas PMII fractions contain mitochondria, lysomes, and plasma membrane vesicles. Approximately 30-40% of the adenylate and guanylate cyclase activities in PMII can be converted to a PMI-like form following dialysis and resedimentation through a second nonlinear sucrose gradient. Adenylate and guanulate cyclases can be distinguished on the basis of sensitivity to nonionic detergents."}
{"id": "PMID:4091", "title": "Fluorine-19 nuclear magnetic resonance study of fluorotyrosine alkaline phosphatase: the influence of zinc on protein structure and a conformational change induced by phosphate binding.", "content": "19F nuclear magnetic resonance (NMR) spectroscopy has been used to study a fully active E. coli fluorotyrosine alkaline phosphatase. The fluorotyrosine resonances provide sensitive probes of the conformational states of the protein. They were used to follow the addition of zinc or cobalt to the apoprotein, and the titration of the protein with inorganic phosphate or the inhibitor 2-hydroxy-5-nitrobenzylphosphonate. The results indicate that 2 molecules of inorganic phosphate per dimer of alkaline phosphatase are required to complete a general conformational change in the protein involving perturbations to the environment of several tyrosines. Spectra of the cobalt enzyme indicate that on specific tyrosine per subunit may be near the metal site. The 19F NMR results, combined with the 31P NMR results in the accompanying paper, lead directly to the conclusion  that dissociation of noncovalently bound inorganic phosphate from the enzyme is the rate-limiting process in enzyme catalysis at high pH. The local environment of the individual fluorotyrosines is also discussed.", "contents": "Fluorine-19 nuclear magnetic resonance study of fluorotyrosine alkaline phosphatase: the influence of zinc on protein structure and a conformational change induced by phosphate binding. 19F nuclear magnetic resonance (NMR) spectroscopy has been used to study a fully active E. coli fluorotyrosine alkaline phosphatase. The fluorotyrosine resonances provide sensitive probes of the conformational states of the protein. They were used to follow the addition of zinc or cobalt to the apoprotein, and the titration of the protein with inorganic phosphate or the inhibitor 2-hydroxy-5-nitrobenzylphosphonate. The results indicate that 2 molecules of inorganic phosphate per dimer of alkaline phosphatase are required to complete a general conformational change in the protein involving perturbations to the environment of several tyrosines. Spectra of the cobalt enzyme indicate that on specific tyrosine per subunit may be near the metal site. The 19F NMR results, combined with the 31P NMR results in the accompanying paper, lead directly to the conclusion  that dissociation of noncovalently bound inorganic phosphate from the enzyme is the rate-limiting process in enzyme catalysis at high pH. The local environment of the individual fluorotyrosines is also discussed."}
{"id": "PMID:4092", "title": "31P nuclear magnetic resonance study of alkaline phosphatase: the role of inorganic phosphate in limiting the enzyme turnover rate at alkaline pH.", "content": "31P nuclear magnetic resonance (NMR) was used to directly observe the binding of inorganic phosphate to alkaline phosphatase. Evidencq for the tight binding of 1.5-2.0 mol of inorganic phosphate per dimer of alkaline phosphatase is presented. Two distinct forms of bound phosphate are observed, one predominating above pH 7 and representing the non-covalent E-P1 complex and the other predominating below pH 5 and representing the covalent E-P1 complex. The 31P NMR line width of the E-P1 complex indicates that the dissociation of noncovalent phosphate is the rate-limiting step in the turnover of the enzyme at high pH.", "contents": "31P nuclear magnetic resonance study of alkaline phosphatase: the role of inorganic phosphate in limiting the enzyme turnover rate at alkaline pH. 31P nuclear magnetic resonance (NMR) was used to directly observe the binding of inorganic phosphate to alkaline phosphatase. Evidencq for the tight binding of 1.5-2.0 mol of inorganic phosphate per dimer of alkaline phosphatase is presented. Two distinct forms of bound phosphate are observed, one predominating above pH 7 and representing the non-covalent E-P1 complex and the other predominating below pH 5 and representing the covalent E-P1 complex. The 31P NMR line width of the E-P1 complex indicates that the dissociation of noncovalent phosphate is the rate-limiting step in the turnover of the enzyme at high pH."}
{"id": "PMID:4093", "title": "An analysis of the autophosphorylation of rabbit and human erythrocyte membranes.", "content": "The autophosphorylation of rabbit and human erythrocyte membranes has been studied under various experimental conditions. The phosphopeptides of the erythocyte membranes were identified using sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis followed by ratioautography. The pattern of phosphorylatiion of membrane components differs with respect to the phosphoryl donor used (ATP or GTP) and to the pH at which the reaction is carried out. Both species appear to contain at least two distinct membrane-bound protein kinases. The human erythrocyte membrane contains a cyclic adenosine 3'5'-monophosphate (cyclic AMP)-dependent protein kinase and several substrates for this kinase. Only ATP can be used as a phosphoryl donor for this kinase. In contrast, the rabbit erythrocyte membrane does not contain a cyclic AMP dependent protein kinase but does contain a kinase which utilizes only ATP as the phosphoryl donor and is specific for certain endogenous substrates at low pH. Both the human and  rabbit erythrocyte membranes contain a kinase which utilizes GTP, perhaps also ATP, as the phosphoryl donor. The substrates of these kinases are similar in both species.", "contents": "An analysis of the autophosphorylation of rabbit and human erythrocyte membranes. The autophosphorylation of rabbit and human erythrocyte membranes has been studied under various experimental conditions. The phosphopeptides of the erythocyte membranes were identified using sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis followed by ratioautography. The pattern of phosphorylatiion of membrane components differs with respect to the phosphoryl donor used (ATP or GTP) and to the pH at which the reaction is carried out. Both species appear to contain at least two distinct membrane-bound protein kinases. The human erythrocyte membrane contains a cyclic adenosine 3'5'-monophosphate (cyclic AMP)-dependent protein kinase and several substrates for this kinase. Only ATP can be used as a phosphoryl donor for this kinase. In contrast, the rabbit erythrocyte membrane does not contain a cyclic AMP dependent protein kinase but does contain a kinase which utilizes only ATP as the phosphoryl donor and is specific for certain endogenous substrates at low pH. Both the human and  rabbit erythrocyte membranes contain a kinase which utilizes GTP, perhaps also ATP, as the phosphoryl donor. The substrates of these kinases are similar in both species."}
{"id": "PMID:4094", "title": "Glutamine synthetase adenylyltransferase from Escherichia coli: purification and physical and chemical properties.", "content": "The glutamine synthetase adenylyltransferase (EC 2.7.7.42), WHIch catalyzes the adenylylation and deadenylylation of glutamine synthetase in E. coli, has been stabilized and purified 2200-fold to apparent homogeneity. Sedimentation and electrophoresis studies show that the native enzyme is a single polypeptide chain of 115,000 +/- 5000 molecular weight with an isoelectric pH (PL) OF 4.98, a sedimentation coefficient (S20.w0) of 5.6S, and a molar frictional coefficient (f/f0) of 1.52. An alpha-helical content of approximately equal to 25% and approximately equal to 28% beta-pleated sheet and approximately equal to 47% random coil structures were estimated from circular dichroism measurements. The amino acid composition of the protein has been determined. The intrinsic tryptophanyl residue flourescence of adenylyltransferase is two fold greater than that of L-tryptophan; this property has been used to monitor ligand-induced conformational changes in the enzyme. Activators of the adenylylation reaction (ATP, L-glutamine, or the E. coli PII regulatory protein) produced an enhancement of fluorescence; alpha-ketoglutarate, an inhibitor of adenylylation and an activator of deadenulylation, caused a net decrease in fluorescence. The adenylytransferase has separate interaction sites for L-glutamine and the regulatory PII protein.", "contents": "Glutamine synthetase adenylyltransferase from Escherichia coli: purification and physical and chemical properties. The glutamine synthetase adenylyltransferase (EC 2.7.7.42), WHIch catalyzes the adenylylation and deadenylylation of glutamine synthetase in E. coli, has been stabilized and purified 2200-fold to apparent homogeneity. Sedimentation and electrophoresis studies show that the native enzyme is a single polypeptide chain of 115,000 +/- 5000 molecular weight with an isoelectric pH (PL) OF 4.98, a sedimentation coefficient (S20.w0) of 5.6S, and a molar frictional coefficient (f/f0) of 1.52. An alpha-helical content of approximately equal to 25% and approximately equal to 28% beta-pleated sheet and approximately equal to 47% random coil structures were estimated from circular dichroism measurements. The amino acid composition of the protein has been determined. The intrinsic tryptophanyl residue flourescence of adenylyltransferase is two fold greater than that of L-tryptophan; this property has been used to monitor ligand-induced conformational changes in the enzyme. Activators of the adenylylation reaction (ATP, L-glutamine, or the E. coli PII regulatory protein) produced an enhancement of fluorescence; alpha-ketoglutarate, an inhibitor of adenylylation and an activator of deadenulylation, caused a net decrease in fluorescence. The adenylytransferase has separate interaction sites for L-glutamine and the regulatory PII protein."}
{"id": "PMID:4095", "title": "The esterification of dolichol by rat liver microsomes.", "content": "The incubation of 1-[3H)dolichols with cell-free preparations from various rat tissues resulted in the formation of a labeled material which possessed the characteristics of synthetic dolichol palmitate. Rat liver microsomes were found to be a good source of the acyltransferase activity, and the properties of the reaction were investigated using microsomal preparations. The reaction did not require ATP, CoA, or Mg2+ and was stimulated by the addition of phosphatidylcholine. The esterification of dolichol appears to be similar to the esterification of retinol. The fact that the esterification of dolichol is not depressed even in the presence of a several-fold excess of retinol is evidence that the two reactions are catalyzed by different enzymes.", "contents": "The esterification of dolichol by rat liver microsomes. The incubation of 1-[3H)dolichols with cell-free preparations from various rat tissues resulted in the formation of a labeled material which possessed the characteristics of synthetic dolichol palmitate. Rat liver microsomes were found to be a good source of the acyltransferase activity, and the properties of the reaction were investigated using microsomal preparations. The reaction did not require ATP, CoA, or Mg2+ and was stimulated by the addition of phosphatidylcholine. The esterification of dolichol appears to be similar to the esterification of retinol. The fact that the esterification of dolichol is not depressed even in the presence of a several-fold excess of retinol is evidence that the two reactions are catalyzed by different enzymes."}
{"id": "PMID:4096", "title": "Preparation of Fv fragment from the mouse myeloma XRPC-25 immunoglobulin possessing anti-dinitrophenyl activity.", "content": "The myeloma IgA protein produced by plasmacytoma XRPC-25, was isolated by affinity chromatography on dinitrophenyllysine-Sepharose. The affinity constant of the intact protein or its Fab' toward 2,4-dinitrophenyl-L-lysine (Dnp) was found to be 2.6 X 10(5) M-1. In order to prepare an Fv fragment (Hochman, J., Inbar, D., and Givol, D. (1973), Biochemistry 12, 1130) from this protein, the heavy and light chains were separated and the light chain was digested with trypsin at pH 8.2 to yield half a light chain. This digest was reassociated with the heavy chain and the recombinant was digested with papain at pH 5.7. Fractionation of this digest on a Sephadex G-75 column and Dnp-lysine-Sepharose resulted in the isolation of an Fv fragment which possesses one binding site for Dnplysine (Ka = 2.0 X 10(5) M-1). The active Fv fragment has a molecular weight of 23,400 and is composed of two peptide chains, each having a molecular weight of approximately 12,000. The N-terminal residues of these chains are aspartic and glutamic acids, which are also N-terminal in the heavy and light chains, indicating that the Fv is composed of VL and VH.", "contents": "Preparation of Fv fragment from the mouse myeloma XRPC-25 immunoglobulin possessing anti-dinitrophenyl activity. The myeloma IgA protein produced by plasmacytoma XRPC-25, was isolated by affinity chromatography on dinitrophenyllysine-Sepharose. The affinity constant of the intact protein or its Fab' toward 2,4-dinitrophenyl-L-lysine (Dnp) was found to be 2.6 X 10(5) M-1. In order to prepare an Fv fragment (Hochman, J., Inbar, D., and Givol, D. (1973), Biochemistry 12, 1130) from this protein, the heavy and light chains were separated and the light chain was digested with trypsin at pH 8.2 to yield half a light chain. This digest was reassociated with the heavy chain and the recombinant was digested with papain at pH 5.7. Fractionation of this digest on a Sephadex G-75 column and Dnp-lysine-Sepharose resulted in the isolation of an Fv fragment which possesses one binding site for Dnplysine (Ka = 2.0 X 10(5) M-1). The active Fv fragment has a molecular weight of 23,400 and is composed of two peptide chains, each having a molecular weight of approximately 12,000. The N-terminal residues of these chains are aspartic and glutamic acids, which are also N-terminal in the heavy and light chains, indicating that the Fv is composed of VL and VH."}
{"id": "PMID:4097", "title": "Purification and properties of a low molecular weight protein factor of mitochondrial energy-linked functions.", "content": "1. A soluble protein with a molecular weight of 11-12-10(3) has been isolated from bovine-heart mitochondria, which stimulates the following ATP-dependent reactions of submitochondrial particles treated with 0.6 mM EDTA and 1 M NH4OH: reverse electron transfer from succinate to NAD, transhydrogenation from NADH to NADP, and ATP-Pi exchange. The factor has no effect on the NADH oxidase, succinate oxidase and ATPase activities of the particles. 2. The stimulatory effect of the factor in the ATP-dependent reduction of NAD by succinate is 12 mumol-min-1-mg-1 of the factor protein. However, the NH4OH-EDTA treated particles are saturated for maximal activation of the above reaction by very small amounts of the factor (about 20-40 mug factor per mg particle). 3. Electrophoresis of the factor preparation on polyacrylamide gels showed a single protein band plus a nonprotein material which moved at the dye front and was weakly stained with Coomassie Blue. The protein was shown to be required for activation of the particles; whether the fast-moving, nonprotein material is also required is not known. 4. The factor is inhibited by mercurials and N-ethylmaleimide. The former, but not the latter, inhibition is completely reversed by 1,4-dithiothreitol. 5. The NH4OH-EDTA treated particles are also stimulated by rutamycin up to about 0.1 nmol of rutamycin per mg particle; higher rutamycin concentrations inhibit. Depending on the particle preparation, the factor stimulates up to about 3 nmol per mg particle, but does not inhibit at higher concentrations. In addition, under certain conditions in which appropriate concentrations of rutamycin fail to stimulate the particles, the factor still does.", "contents": "Purification and properties of a low molecular weight protein factor of mitochondrial energy-linked functions. 1. A soluble protein with a molecular weight of 11-12-10(3) has been isolated from bovine-heart mitochondria, which stimulates the following ATP-dependent reactions of submitochondrial particles treated with 0.6 mM EDTA and 1 M NH4OH: reverse electron transfer from succinate to NAD, transhydrogenation from NADH to NADP, and ATP-Pi exchange. The factor has no effect on the NADH oxidase, succinate oxidase and ATPase activities of the particles. 2. The stimulatory effect of the factor in the ATP-dependent reduction of NAD by succinate is 12 mumol-min-1-mg-1 of the factor protein. However, the NH4OH-EDTA treated particles are saturated for maximal activation of the above reaction by very small amounts of the factor (about 20-40 mug factor per mg particle). 3. Electrophoresis of the factor preparation on polyacrylamide gels showed a single protein band plus a nonprotein material which moved at the dye front and was weakly stained with Coomassie Blue. The protein was shown to be required for activation of the particles; whether the fast-moving, nonprotein material is also required is not known. 4. The factor is inhibited by mercurials and N-ethylmaleimide. The former, but not the latter, inhibition is completely reversed by 1,4-dithiothreitol. 5. The NH4OH-EDTA treated particles are also stimulated by rutamycin up to about 0.1 nmol of rutamycin per mg particle; higher rutamycin concentrations inhibit. Depending on the particle preparation, the factor stimulates up to about 3 nmol per mg particle, but does not inhibit at higher concentrations. In addition, under certain conditions in which appropriate concentrations of rutamycin fail to stimulate the particles, the factor still does."}
{"id": "PMID:4098", "title": "Effect of the transmembrane electric field on the photochemical and quenching properties of photosystem II in vivo.", "content": "The intermediate phase of fluorescence relaxation (lms-ls) (Joliot, P., Joliot, A., Bouges, B, and Barbieri, G. (1971) Photochem. Photobiol. 14, 287-305), following a single saturating flash, is shown to be controlled by a slow phase of the reoxidation of Q- by a secondary acceptor and, in vivo, by the transmembrane electric field. The kinetics of reoxidation of Q- are slowed by lowering the pH. This slowing effect is interpreted in terms of the reversible formation at low pH of QH which is not oxidizable by the secondary acceptor. The electric field transforms Photosystem II centers into a non-quenching photochemically inactive state that cannot be attributed to an accumulation of Q-. Centers are unequally sensitive to the field. A critical field strength can be defined for each center above which that center is blocked and below which the center is photochemically active. The transformation from the active to inactive state occurs over a narrow range of field strength. Sensitive centers are blocked by the field in less than 1 ms and become active again in less than 10 ms as the field strength falls. Two hypotheses are proposed for the mechanism of blockage of centers by the field: (1) a field induced conformational change in the centers, (2) the formation or suppression of a dipole critical to the function of a center. The activity of the ATP synthetase, determining the rate of relaxation of the field, was controlled by a light-dark treatment or by a chemical method using p-benzoquinone.", "contents": "Effect of the transmembrane electric field on the photochemical and quenching properties of photosystem II in vivo. The intermediate phase of fluorescence relaxation (lms-ls) (Joliot, P., Joliot, A., Bouges, B, and Barbieri, G. (1971) Photochem. Photobiol. 14, 287-305), following a single saturating flash, is shown to be controlled by a slow phase of the reoxidation of Q- by a secondary acceptor and, in vivo, by the transmembrane electric field. The kinetics of reoxidation of Q- are slowed by lowering the pH. This slowing effect is interpreted in terms of the reversible formation at low pH of QH which is not oxidizable by the secondary acceptor. The electric field transforms Photosystem II centers into a non-quenching photochemically inactive state that cannot be attributed to an accumulation of Q-. Centers are unequally sensitive to the field. A critical field strength can be defined for each center above which that center is blocked and below which the center is photochemically active. The transformation from the active to inactive state occurs over a narrow range of field strength. Sensitive centers are blocked by the field in less than 1 ms and become active again in less than 10 ms as the field strength falls. Two hypotheses are proposed for the mechanism of blockage of centers by the field: (1) a field induced conformational change in the centers, (2) the formation or suppression of a dipole critical to the function of a center. The activity of the ATP synthetase, determining the rate of relaxation of the field, was controlled by a light-dark treatment or by a chemical method using p-benzoquinone."}
{"id": "PMID:4099", "title": "Determination of H+/e- ratios in chloroplasts with flashing light.", "content": "Using a rapid pH electrode, measurements were made of the flash-induced proton transport in isolated spinach chloroplasts. To calibrate the system, we assumed that in the presence of ferricyanide and in steady-state flashing light, each flash liberates from water one proton per reaction chain. We concluded that with both ferricyanide and methylviologen as acceptors two protons per electron are translocated by the electron transport chain connecting Photosystem II and I. With methyl viologen but not with ferricyanide as an acceptor, two additional protons per electron are taken up due to Photosystem I activity. One of these latter protons is translocated to the inside of the thylakoid while the other is taken up in H2O2 formation. Assuming that the proton released during water splitting remains inside the thylakoid, we compute H+/e- ratios of 3 and 4 for ferricyanide and methylviologen, respectively. In continuous light of low intensity, we obtained the same H+/e- ratios. However, with higher intensities where electron transport becomes rate limited by the internal pH, the H+/e- ratio approached 2 as a limit for both acceptors. A working model is presented which includes two sites of proton translocation, one between the photoacts, the other connected to Photosystem I, each of which translocates two protons per electron. Each site presents a approximately 30 ms diffusion barrier to proton passage which can be lowered by uncouplers to 6-10 ms.", "contents": "Determination of H+/e- ratios in chloroplasts with flashing light. Using a rapid pH electrode, measurements were made of the flash-induced proton transport in isolated spinach chloroplasts. To calibrate the system, we assumed that in the presence of ferricyanide and in steady-state flashing light, each flash liberates from water one proton per reaction chain. We concluded that with both ferricyanide and methylviologen as acceptors two protons per electron are translocated by the electron transport chain connecting Photosystem II and I. With methyl viologen but not with ferricyanide as an acceptor, two additional protons per electron are taken up due to Photosystem I activity. One of these latter protons is translocated to the inside of the thylakoid while the other is taken up in H2O2 formation. Assuming that the proton released during water splitting remains inside the thylakoid, we compute H+/e- ratios of 3 and 4 for ferricyanide and methylviologen, respectively. In continuous light of low intensity, we obtained the same H+/e- ratios. However, with higher intensities where electron transport becomes rate limited by the internal pH, the H+/e- ratio approached 2 as a limit for both acceptors. A working model is presented which includes two sites of proton translocation, one between the photoacts, the other connected to Photosystem I, each of which translocates two protons per electron. Each site presents a approximately 30 ms diffusion barrier to proton passage which can be lowered by uncouplers to 6-10 ms."}
{"id": "PMID:4100", "title": "[Study of the mechanism of the effect of extracellular pH on the synthesis of the oxidative complex (cytochrome a+a3) of Bacillus coagulans: relationship to the \"glucose effect\" and role of excreted coproporphyrin III (author's transl)].", "content": "During the \"respiratory adaptation\" of Bacillus coagulans, it was possible to dissociate the kinetics of cytochrome a and a3 synthesis with carbon monoxide. The synthesis of cytochrome a3 is preferentially repressed when the pH of the incubation medium is pH 6.5 instead of pH 5.5. However, though the total synthesis of tetrapyrrole compounds is the same at both pH values, the excretion of coproporphyrin III is much increased at pH 6.5. Bacillus coagulans, sensitive to the \"glucose effect\", shows the \"pH effect\" only in the presence of high glucose concentrations. The repression of the oxidase complex synthesis by a slight increase of the extracellular pH appears directly related to the increase of the extracellular coproporphyrin III.", "contents": "[Study of the mechanism of the effect of extracellular pH on the synthesis of the oxidative complex (cytochrome a+a3) of Bacillus coagulans: relationship to the \"glucose effect\" and role of excreted coproporphyrin III (author's transl)]. During the \"respiratory adaptation\" of Bacillus coagulans, it was possible to dissociate the kinetics of cytochrome a and a3 synthesis with carbon monoxide. The synthesis of cytochrome a3 is preferentially repressed when the pH of the incubation medium is pH 6.5 instead of pH 5.5. However, though the total synthesis of tetrapyrrole compounds is the same at both pH values, the excretion of coproporphyrin III is much increased at pH 6.5. Bacillus coagulans, sensitive to the \"glucose effect\", shows the \"pH effect\" only in the presence of high glucose concentrations. The repression of the oxidase complex synthesis by a slight increase of the extracellular pH appears directly related to the increase of the extracellular coproporphyrin III."}
{"id": "PMID:4101", "title": "The effect of retinol and retinoic acid on the testicular phospholipase a activity in retinol-deficient rats.", "content": "Both phospholipases A1 and A2 activities (EC 3.1.1.4) at pH 7.4 were found to be significantly decreased in retinol-deficient rat testes supplemented with retinoic acid as compared to retinol-fed controls using 1-acyl-2-[1-(14)C]-oleoyl-sn-glycero-3-phosphocholine as substrate. However, little or no difference was observed in phospholipase A1 activity at pH 3.0 in both groups of rats.", "contents": "The effect of retinol and retinoic acid on the testicular phospholipase a activity in retinol-deficient rats. Both phospholipases A1 and A2 activities (EC 3.1.1.4) at pH 7.4 were found to be significantly decreased in retinol-deficient rat testes supplemented with retinoic acid as compared to retinol-fed controls using 1-acyl-2-[1-(14)C]-oleoyl-sn-glycero-3-phosphocholine as substrate. However, little or no difference was observed in phospholipase A1 activity at pH 3.0 in both groups of rats."}
{"id": "PMID:4102", "title": "Enzymatic properties of cloacin DF13 and kinetics of ribosome inactivation.", "content": "1. The cloacin DF13-induced inactivation of ribosomes in vitro can be described as an enzyme-catalyzed reaction according to the Michaelis-Menten equation. Most probably the cloacin acts as a unique endoribonuclease. 2. At pH 7.8 and 37 degrees C the Km value for the reaction of cloacin DF13 with ribosomes is 13.2 - 10(-6) M. If under these conditions the reaction mixture is supplemented with all components necessary for protein synthesis, the Km changes to 17.7 - 10(-6) M. 3. The in vitro activity of cloacin DF13 has a temperature optimum of 43 degrees C at pH 7.8 and a pH optimum of 8.4 at 37 degtees C. 4. Experiments with cloacin DF13-immunity protein as an inhibitor of the cloacin activity in vitro have indicated that the immunity protein might be considered as a non-competitive and virtually \"irreversible\" inhibitor.", "contents": "Enzymatic properties of cloacin DF13 and kinetics of ribosome inactivation. 1. The cloacin DF13-induced inactivation of ribosomes in vitro can be described as an enzyme-catalyzed reaction according to the Michaelis-Menten equation. Most probably the cloacin acts as a unique endoribonuclease. 2. At pH 7.8 and 37 degrees C the Km value for the reaction of cloacin DF13 with ribosomes is 13.2 - 10(-6) M. If under these conditions the reaction mixture is supplemented with all components necessary for protein synthesis, the Km changes to 17.7 - 10(-6) M. 3. The in vitro activity of cloacin DF13 has a temperature optimum of 43 degrees C at pH 7.8 and a pH optimum of 8.4 at 37 degtees C. 4. Experiments with cloacin DF13-immunity protein as an inhibitor of the cloacin activity in vitro have indicated that the immunity protein might be considered as a non-competitive and virtually \"irreversible\" inhibitor."}
{"id": "PMID:4103", "title": "Transfer RNA methyltransferase activity in paramecium aurelia.", "content": "The tRNA methyltransferases from Paramecium aurelia were investigated. The effects of varying the Mg2+ and NH4+ concentrations, pH, and temperature on the methylation of Escherichia coli B tRNA using extracts from P. aurelia were determined. Optimum tRNA methyltransferase activity was observed at pH 7.8 and 37 degrees C. The Mg2+ optimum occurred at 0.66 mM in the absence of NH4+ while the NH4+ optimum occurred at 100 mM in the absence of Mg2+. Analysis of the bases methylated in (E. coli B) tRNA by extracts of P. aurelia showed the presence of 1-methyladenine, 1-methylguanine, N2-methylguanine, N2,N2-dimethylguanine and methylated pyrimidine nucleotides. In comparison, an analysis of the in vivo methylation of tRNA from P. aurelia showed the presence of 1-methyladenine, 6-methyladenine, 6,6-dimethyladenine, 1-methylguanine, N2-methylguanine, N2,N2-dimethylguanine, 7-methylguanine, and methylated pyrimidine nucleotides. The pattern of methylation of tRNA in P. aurelia is similar to that observed in other eukaryotes.", "contents": "Transfer RNA methyltransferase activity in paramecium aurelia. The tRNA methyltransferases from Paramecium aurelia were investigated. The effects of varying the Mg2+ and NH4+ concentrations, pH, and temperature on the methylation of Escherichia coli B tRNA using extracts from P. aurelia were determined. Optimum tRNA methyltransferase activity was observed at pH 7.8 and 37 degrees C. The Mg2+ optimum occurred at 0.66 mM in the absence of NH4+ while the NH4+ optimum occurred at 100 mM in the absence of Mg2+. Analysis of the bases methylated in (E. coli B) tRNA by extracts of P. aurelia showed the presence of 1-methyladenine, 1-methylguanine, N2-methylguanine, N2,N2-dimethylguanine and methylated pyrimidine nucleotides. In comparison, an analysis of the in vivo methylation of tRNA from P. aurelia showed the presence of 1-methyladenine, 6-methyladenine, 6,6-dimethyladenine, 1-methylguanine, N2-methylguanine, N2,N2-dimethylguanine, 7-methylguanine, and methylated pyrimidine nucleotides. The pattern of methylation of tRNA in P. aurelia is similar to that observed in other eukaryotes."}
{"id": "PMID:4104", "title": "The effect of silver ion binding and pH on the buoyant density of DNA and its use in fractionating heterogeneous DNA.", "content": "1. The effect of pH on the buoyant density of the complexes of Ag+ with DNA has been studied using 3H-labeled human DNA and several bacterial DNAs to determine the conditions necessary for the maximum resolution of compositional heterogeneity. In neutral CS2SO4 density gradients, Ag+ complexes with (G - C)-rich components are always denser than those with (A - T)-rich components, since (G - C)rich DNAs have a larger affinity for Ag+ than (A - T)-rich DNAs and their complexes are denser than (A - T)-rich complexes. In alkaline (pH greater than 9) CS2SO4 gradients, the buoyant density of the Ag+ - DNA complex is not a simple function of base composition. The Ag+ affinity of (A - T)-rich DNA is larger than that of (G - C)-rich DNA but the density of a (G - C)-rich complex is larger. Thus the ordering of the buoyant density changes depends on the amount of added Ag+. 2. The problem of resolving the density heterogeneity within a tracer DNA, and minor components of DNA, is explored and useful fractionation techniques are developed.", "contents": "The effect of silver ion binding and pH on the buoyant density of DNA and its use in fractionating heterogeneous DNA. 1. The effect of pH on the buoyant density of the complexes of Ag+ with DNA has been studied using 3H-labeled human DNA and several bacterial DNAs to determine the conditions necessary for the maximum resolution of compositional heterogeneity. In neutral CS2SO4 density gradients, Ag+ complexes with (G - C)-rich components are always denser than those with (A - T)-rich components, since (G - C)rich DNAs have a larger affinity for Ag+ than (A - T)-rich DNAs and their complexes are denser than (A - T)-rich complexes. In alkaline (pH greater than 9) CS2SO4 gradients, the buoyant density of the Ag+ - DNA complex is not a simple function of base composition. The Ag+ affinity of (A - T)-rich DNA is larger than that of (G - C)-rich DNA but the density of a (G - C)-rich complex is larger. Thus the ordering of the buoyant density changes depends on the amount of added Ag+. 2. The problem of resolving the density heterogeneity within a tracer DNA, and minor components of DNA, is explored and useful fractionation techniques are developed."}
{"id": "PMID:4105", "title": "Comparison of purple membrane from Halobacterium cutirubrum and Halobacterium halabium.", "content": "Direct comparison of purple membrane preparations from Halobacterium cutirubrum and Halobacterium halobium was carried out. Both preparations were found to be essentially identical with respect to their molecular weight, retinal content, lipid composition, fingerprinting of peptides from peptide digestion, electron micrographs and X-ray diffraction patterns, and behaviour as a light-activated proton pump. Thus, there would appear to be no species differences in the purple membranes from these two bacteria.", "contents": "Comparison of purple membrane from Halobacterium cutirubrum and Halobacterium halabium. Direct comparison of purple membrane preparations from Halobacterium cutirubrum and Halobacterium halobium was carried out. Both preparations were found to be essentially identical with respect to their molecular weight, retinal content, lipid composition, fingerprinting of peptides from peptide digestion, electron micrographs and X-ray diffraction patterns, and behaviour as a light-activated proton pump. Thus, there would appear to be no species differences in the purple membranes from these two bacteria."}
{"id": "PMID:4106", "title": "Kinetics of ion translocation across charged membranes mediated by a two-site transport mechanism. Effects of polyvalent cations upon rubidium uptake into yeast cells.", "content": "(1) The effect of surface charge upon the kinetics of monovalent cation translocation via a two-site mechanism is investigated theroretically. (2) According to the model dealt with, typical relations are expected for the dependence of the kinetic parameters of the translocation process upon the concentration of a polyvalent cation, differing essentially from those derived for the case in which the membrane carries no excess charge. (3) Even when a polyvalent cation does not compete with the substrate cation for binding to the translocation sites, apparently competitive inhibition may occur when the membrane is negatively charged. (4) The model is tested experimentally by studying the effects of the polyvalent cations Mg2+, Sr2+, Ca2+, Ba2+ and Al3+ upon Rb+ uptake into yeast cells at pH 4.5 A good applicability is found. (5) Equimolar concentrations of polyvalent cations reduce the rate of the Rb+ uptake into yeast cells in the order Mg2+ less than Sr2+ less than Ca2+ less than Ba2+ less than Al3+. (6) The conclusion is reached that the reduction in the rate of Rb+ uptake caused by the polyvalent cations applied results mainly from screening of the negative fixed charges on the membrane surface and binding to these negative sites rather than competition with Rb+ for the transport sites. (7) The results of our investigation indicate the affinity of the alkaline-earth cations for the negative fixed charges on the surface to the yeast cell membrane increases in the orther Mg2+ less than Sr2 less than Ca2+ less than Ba2+. (8) Probably mainly phosphoryl groups determine the net charge on the membrane of the yeast cell at a medium pH of 4.5.", "contents": "Kinetics of ion translocation across charged membranes mediated by a two-site transport mechanism. Effects of polyvalent cations upon rubidium uptake into yeast cells. (1) The effect of surface charge upon the kinetics of monovalent cation translocation via a two-site mechanism is investigated theroretically. (2) According to the model dealt with, typical relations are expected for the dependence of the kinetic parameters of the translocation process upon the concentration of a polyvalent cation, differing essentially from those derived for the case in which the membrane carries no excess charge. (3) Even when a polyvalent cation does not compete with the substrate cation for binding to the translocation sites, apparently competitive inhibition may occur when the membrane is negatively charged. (4) The model is tested experimentally by studying the effects of the polyvalent cations Mg2+, Sr2+, Ca2+, Ba2+ and Al3+ upon Rb+ uptake into yeast cells at pH 4.5 A good applicability is found. (5) Equimolar concentrations of polyvalent cations reduce the rate of the Rb+ uptake into yeast cells in the order Mg2+ less than Sr2+ less than Ca2+ less than Ba2+ less than Al3+. (6) The conclusion is reached that the reduction in the rate of Rb+ uptake caused by the polyvalent cations applied results mainly from screening of the negative fixed charges on the membrane surface and binding to these negative sites rather than competition with Rb+ for the transport sites. (7) The results of our investigation indicate the affinity of the alkaline-earth cations for the negative fixed charges on the surface to the yeast cell membrane increases in the orther Mg2+ less than Sr2 less than Ca2+ less than Ba2+. (8) Probably mainly phosphoryl groups determine the net charge on the membrane of the yeast cell at a medium pH of 4.5."}
{"id": "PMID:4107", "title": "The structure of monellin and its relation to the sweetness of the protein.", "content": "The sweet protein monellin [1-3] has been shown to consist of two non-identical subunits of 50 and 42 amino acid residues, which were separated electrophoretically and chromatographically. Automatic sequential Edman degradation gave the complete sequence of the longer subunit, and a partial sequency of the shorter one. It was found that the sweetness of monellin requires the undissociated molecule. The individual subunits were not sweet, neither did they block the sweet sensation of sucrose or monellin. Blocking of the single SH of monellin abolished its sweetness as did reaction of the single methionyl residue with CNBr. Since the cysteinyl and methionyl residues appear to be adjacent, it is suggested that this part of the molecule is essential for its sweetness.", "contents": "The structure of monellin and its relation to the sweetness of the protein. The sweet protein monellin [1-3] has been shown to consist of two non-identical subunits of 50 and 42 amino acid residues, which were separated electrophoretically and chromatographically. Automatic sequential Edman degradation gave the complete sequence of the longer subunit, and a partial sequency of the shorter one. It was found that the sweetness of monellin requires the undissociated molecule. The individual subunits were not sweet, neither did they block the sweet sensation of sucrose or monellin. Blocking of the single SH of monellin abolished its sweetness as did reaction of the single methionyl residue with CNBr. Since the cysteinyl and methionyl residues appear to be adjacent, it is suggested that this part of the molecule is essential for its sweetness."}
{"id": "PMID:4108", "title": "Anomalous fluorescence of yeast 3-phosphoglucerate kinase.", "content": "The 3-phosphoglycerate kinase (EC 2.7.2.3) of yeast which contains two tryptophyl and eight tyrosyl residues per molecule, displayed an unusualy fluorescence emission spectrum with a maximum at 308 nm when excited at 280 nm. The emission peak shifted to 329 nm when excited at 295 nm. We could confirm that it was due to the efficient quenching of tryptophyl fluorescence as well as to the incomplete energy transfer from tyrosyl to tryptophyl residues. The average fluorescence quantum yield of this protein was 0.076 (excitation at 280 nm) and that of tryptophyl residues was 0.046 (excitation at 295 nm). As the pH of the solution was lowered, the fluorescence intensity of phosphoglycerate kinase at 329 nm dramatically increased between pH 5 and 4, while the position of the peak remained unchanged. When denatured in 4 M guanidine hydrochloride, the protein showed two emission peaks, one at 343 nm and the other at 303 nm.", "contents": "Anomalous fluorescence of yeast 3-phosphoglucerate kinase. The 3-phosphoglycerate kinase (EC 2.7.2.3) of yeast which contains two tryptophyl and eight tyrosyl residues per molecule, displayed an unusualy fluorescence emission spectrum with a maximum at 308 nm when excited at 280 nm. The emission peak shifted to 329 nm when excited at 295 nm. We could confirm that it was due to the efficient quenching of tryptophyl fluorescence as well as to the incomplete energy transfer from tyrosyl to tryptophyl residues. The average fluorescence quantum yield of this protein was 0.076 (excitation at 280 nm) and that of tryptophyl residues was 0.046 (excitation at 295 nm). As the pH of the solution was lowered, the fluorescence intensity of phosphoglycerate kinase at 329 nm dramatically increased between pH 5 and 4, while the position of the peak remained unchanged. When denatured in 4 M guanidine hydrochloride, the protein showed two emission peaks, one at 343 nm and the other at 303 nm."}
{"id": "PMID:4109", "title": "Binding of norgestrel to human plasma proteins.", "content": "Binding of [14, 15-3H](+/-)-norgestrel to human plasma proteins has been investigated. Norgestrel showed greater affinity to plasma than to human serum albumin indicating specific norgestrel binding protein(s) in the plasma. alpha1-acid glycoprotein showed high affinity for norgestrel when compared with human serum albumin. The binding protein was eluted at pH 5.8 by step by step elution on a DEAE-cellulose column. Norgestrel binding to plasma proteins was not affected at 60 degrees C. The optimal binding occurred between pH 7 and 8. Ligand specificity of the binding protein revealed that progesterone was able to compete for the norgestrel binding sites, whereas corticosterone, testosterone, oestradiol, and norethindrone acetate did not show much competition. The molecular weight of the binding protein was found to be approximately 43 000. Sucrose density gradient analysis indicated that norgestrel bound to a macromolecular component of sedimentation coefficient 2.9 S. The association constant (Kass) and dissociation constant (Kdiss) of norgestrel-binding plasma protein was found to be 1.4-10(6) M-1 and 0.7-10(-6) M respectively. The number of binding sites was 0.5-10(-9) mol/mg protein. Norgestrel-binding protein in the plasma appeared to be a protein different from human serum albumin, corticosteroid-binding globulin and sex-steroid-binding protein. This binding protein showed some similarities to alpha1-acid glycoprotein.", "contents": "Binding of norgestrel to human plasma proteins. Binding of [14, 15-3H](+/-)-norgestrel to human plasma proteins has been investigated. Norgestrel showed greater affinity to plasma than to human serum albumin indicating specific norgestrel binding protein(s) in the plasma. alpha1-acid glycoprotein showed high affinity for norgestrel when compared with human serum albumin. The binding protein was eluted at pH 5.8 by step by step elution on a DEAE-cellulose column. Norgestrel binding to plasma proteins was not affected at 60 degrees C. The optimal binding occurred between pH 7 and 8. Ligand specificity of the binding protein revealed that progesterone was able to compete for the norgestrel binding sites, whereas corticosterone, testosterone, oestradiol, and norethindrone acetate did not show much competition. The molecular weight of the binding protein was found to be approximately 43 000. Sucrose density gradient analysis indicated that norgestrel bound to a macromolecular component of sedimentation coefficient 2.9 S. The association constant (Kass) and dissociation constant (Kdiss) of norgestrel-binding plasma protein was found to be 1.4-10(6) M-1 and 0.7-10(-6) M respectively. The number of binding sites was 0.5-10(-9) mol/mg protein. Norgestrel-binding protein in the plasma appeared to be a protein different from human serum albumin, corticosteroid-binding globulin and sex-steroid-binding protein. This binding protein showed some similarities to alpha1-acid glycoprotein."}
{"id": "PMID:4110", "title": "Equilbrium and kinetics of the unfolding of alpha-lactalbumin by guanidine hydrochloride (II).", "content": "The reversible unfolding of alpha-lactalbumin by guanidine hydrochloride, was studied at 25.0 degrees C in a relatively low concentration range of the denaturant (0.80-2.00 mol/l) by means of difference spectra and pH-jump measurements. The unfolding was shown to occur between two states, N and D, because apparent rate-constants of the unfolding and the refolding reactions depended only on pH. All curves plotted as the logarithmical equilibrium constant log KD against pH could fall on the same base curve by shifting each curve along the log KD axis. From the dependence of the logarithmic rate constant on pH, master curves could also be made for the forward and the backward reactions. The dependence of these master curves on pH indicates that the groups affecting the pH dependence of the unfolding are three residues with pKN = 3.3 and pKA = pKD = 4.4, one residue with pKN = pKA = 3.8 and pKD = 4.4, and one residue with pKN = 5.8 and pKA = pKD = 6.3, where A indicates the activated state. On the other hand, from the denaturant activity dependence of the shift factors required for making the master curves, the value of the intrinsic binding constant of the denaturant to the protein was found to be similar to that obtained from previous measurements at pH 5.5. Differences between the numbers of the binding sites of the denaturant on the denaturated and the native proteins, and between those on the activated and the native proteins were shown to be 5.3 and 2.1, respectively. The free energy of stabilization in the native-like environment also shows that the protein in the native state is more unstable than lysozyme.", "contents": "Equilbrium and kinetics of the unfolding of alpha-lactalbumin by guanidine hydrochloride (II). The reversible unfolding of alpha-lactalbumin by guanidine hydrochloride, was studied at 25.0 degrees C in a relatively low concentration range of the denaturant (0.80-2.00 mol/l) by means of difference spectra and pH-jump measurements. The unfolding was shown to occur between two states, N and D, because apparent rate-constants of the unfolding and the refolding reactions depended only on pH. All curves plotted as the logarithmical equilibrium constant log KD against pH could fall on the same base curve by shifting each curve along the log KD axis. From the dependence of the logarithmic rate constant on pH, master curves could also be made for the forward and the backward reactions. The dependence of these master curves on pH indicates that the groups affecting the pH dependence of the unfolding are three residues with pKN = 3.3 and pKA = pKD = 4.4, one residue with pKN = pKA = 3.8 and pKD = 4.4, and one residue with pKN = 5.8 and pKA = pKD = 6.3, where A indicates the activated state. On the other hand, from the denaturant activity dependence of the shift factors required for making the master curves, the value of the intrinsic binding constant of the denaturant to the protein was found to be similar to that obtained from previous measurements at pH 5.5. Differences between the numbers of the binding sites of the denaturant on the denaturated and the native proteins, and between those on the activated and the native proteins were shown to be 5.3 and 2.1, respectively. The free energy of stabilization in the native-like environment also shows that the protein in the native state is more unstable than lysozyme."}
{"id": "PMID:4111", "title": "Fluorimetric studies of tryptophyl exposure in concanavalin A.", "content": "Studies of the iodide ion quenching of the intrinsic fluorescence of Concanavalin A indicate that 50% of the tryptophyl fluorescence originates from exposed residues. This agrees with the X-ray crystallographic determination that two of the four tryptophan residues in a Concanavalin A monomer are on the surface. Previous studies have indicated that conformational changes induced by sugar binding alter the environment of aromatic residues. The present investigation finds that neither the specific binding of alpha-methyl-D-mannoside nor alteration of the Concanavalin A quaternary structure changes the number or accessibility of the solvent-exposed tryptophan residues. It therefore appears that the major conformational transitions in Concanavalin A do not affect steric access to the surface tryptophans and the effects previously observed may be ascribed to structurally internal tryptophan residues.", "contents": "Fluorimetric studies of tryptophyl exposure in concanavalin A. Studies of the iodide ion quenching of the intrinsic fluorescence of Concanavalin A indicate that 50% of the tryptophyl fluorescence originates from exposed residues. This agrees with the X-ray crystallographic determination that two of the four tryptophan residues in a Concanavalin A monomer are on the surface. Previous studies have indicated that conformational changes induced by sugar binding alter the environment of aromatic residues. The present investigation finds that neither the specific binding of alpha-methyl-D-mannoside nor alteration of the Concanavalin A quaternary structure changes the number or accessibility of the solvent-exposed tryptophan residues. It therefore appears that the major conformational transitions in Concanavalin A do not affect steric access to the surface tryptophans and the effects previously observed may be ascribed to structurally internal tryptophan residues."}
{"id": "PMID:4112", "title": "A study of Folch-Pi apoprotein. II. Relation between polymerization state and conformation.", "content": "A comparison of the conformation of Folch-Pi apoprotein in organic solvent and in aqueous solutions has been made by ESR, infrared and circular dichroism spectroscopy studies. Electrophoresis and ultracentrifugation have been carried out in order to correlate molecular weight and charge of the molecule with its conformation. It appears that the protein is monomeric in organic solution. In water, only one component is present but the molecules behave as a polydisperse system of associating molecules. Hydrophobic interacitons seem to be important for this polymerisation which does not appear to be accompanied by the formation of beta-structure. After the transfer of the protein from organic solution to water, the ESR spectra of the protein labelled on the free SH groups show an heterogeneity in the motional environment of the label which permits to assume that different areas of association exist in the polymeric molecule.", "contents": "A study of Folch-Pi apoprotein. II. Relation between polymerization state and conformation. A comparison of the conformation of Folch-Pi apoprotein in organic solvent and in aqueous solutions has been made by ESR, infrared and circular dichroism spectroscopy studies. Electrophoresis and ultracentrifugation have been carried out in order to correlate molecular weight and charge of the molecule with its conformation. It appears that the protein is monomeric in organic solution. In water, only one component is present but the molecules behave as a polydisperse system of associating molecules. Hydrophobic interacitons seem to be important for this polymerisation which does not appear to be accompanied by the formation of beta-structure. After the transfer of the protein from organic solution to water, the ESR spectra of the protein labelled on the free SH groups show an heterogeneity in the motional environment of the label which permits to assume that different areas of association exist in the polymeric molecule."}
{"id": "PMID:4113", "title": "Response of the glycolysis of human erythrocytes to the transition from the oxygenated to the deoxygenated state at constant intracellular pH.", "content": "The time course of the rate of the glycolysis of human erythrocytes and of some metabolites were determined before and after rapid deoxygenation at constant intracellular pH. For this purpose stripped deoxygenated haemoglobin was used as a rapid oxygen acceptor. Deoxygenation causes an increase of the glycolytic rate by 26%. Glucose 6-phosphate is decreased while the adenine nucleotides and 2,3-bisphosphoglycerate remain constant. Fructose 1,6-bisphosphate and the triose phosphates decrease transiently before rising. The data can be explained by increased binding of phosphocompounds to deoxygenated as compared with oxygenated haemoglobin. Thereby the control enzymes hexokinase and phosphofructokinase are influenced. It is concluded that under physiological conditions changes in the oxygenation state of haemoglobin per se alter the glycolytic rate.", "contents": "Response of the glycolysis of human erythrocytes to the transition from the oxygenated to the deoxygenated state at constant intracellular pH. The time course of the rate of the glycolysis of human erythrocytes and of some metabolites were determined before and after rapid deoxygenation at constant intracellular pH. For this purpose stripped deoxygenated haemoglobin was used as a rapid oxygen acceptor. Deoxygenation causes an increase of the glycolytic rate by 26%. Glucose 6-phosphate is decreased while the adenine nucleotides and 2,3-bisphosphoglycerate remain constant. Fructose 1,6-bisphosphate and the triose phosphates decrease transiently before rising. The data can be explained by increased binding of phosphocompounds to deoxygenated as compared with oxygenated haemoglobin. Thereby the control enzymes hexokinase and phosphofructokinase are influenced. It is concluded that under physiological conditions changes in the oxygenation state of haemoglobin per se alter the glycolytic rate."}
{"id": "PMID:4114", "title": "Intracellular pH of frog sartorius muscle.", "content": "A weak base, morpholine, has been labelled with 3H and tested for its suitability as an indicator for intracellular pH, by distribution in the tissue water of frog sartorius muscle in the species Hyla litoria. Its pK'a at 20 degrees C in a solution of the same ionic strength as frog Ringer was found to be 8.45 +/- 0.02, which is in the range of maximal sensitivity. Morpholine equilibrated with the tissue in 17 h; it was shown that it was not bound to intracellular constituents, that it was not metabolised nor toxic in the concentrations used; it was therefore judged suitable as a pH indcator. Intracellular pH was then measured by distribution of morpholine (6.985 +/- 0.08), nicotine (6.915 +/- 0.03) and the weak acid 5,5'-dimethyl-2,4-oxazolidinedione (7.10 +/- 0.05) and the pH-sensitive microelectrodes (5.9, the equilibrium value). It was shown that the four significantly different values could not be reconciled in terms of experimental error, heterogeneity of intracellular pH, liquid junction potential differences, or binding of indicator molecules inside the fibre. They could, however, be reconciled if the fibre water had different structure and solvent properties from the extracellular water and all ions were distributed across the membrane as between two liquid phases containing different solvents. Then the H+ would be in equilibrium, as shown by the microelectrode measurement, but intracellular pH would be indeterminable and probably greater than 6.", "contents": "Intracellular pH of frog sartorius muscle. A weak base, morpholine, has been labelled with 3H and tested for its suitability as an indicator for intracellular pH, by distribution in the tissue water of frog sartorius muscle in the species Hyla litoria. Its pK'a at 20 degrees C in a solution of the same ionic strength as frog Ringer was found to be 8.45 +/- 0.02, which is in the range of maximal sensitivity. Morpholine equilibrated with the tissue in 17 h; it was shown that it was not bound to intracellular constituents, that it was not metabolised nor toxic in the concentrations used; it was therefore judged suitable as a pH indcator. Intracellular pH was then measured by distribution of morpholine (6.985 +/- 0.08), nicotine (6.915 +/- 0.03) and the weak acid 5,5'-dimethyl-2,4-oxazolidinedione (7.10 +/- 0.05) and the pH-sensitive microelectrodes (5.9, the equilibrium value). It was shown that the four significantly different values could not be reconciled in terms of experimental error, heterogeneity of intracellular pH, liquid junction potential differences, or binding of indicator molecules inside the fibre. They could, however, be reconciled if the fibre water had different structure and solvent properties from the extracellular water and all ions were distributed across the membrane as between two liquid phases containing different solvents. Then the H+ would be in equilibrium, as shown by the microelectrode measurement, but intracellular pH would be indeterminable and probably greater than 6."}
{"id": "PMID:4115", "title": "Activation of murine lymphocytes by cyclic guanosine 3',5'-monophosphate: specificity and role in mitogen activity.", "content": "Cyclic guanosine 3',5'-monophosphate (cyclic GMP) stimulates nucleic acid synthesis in lymphocytes, and has been implicated as the intracellular effector of the actions of mitogenic agents on these cells. In the present study, we examined the specificity of the mitogenic activity of cyclic GMP and of its 8-bromo (Br) derivatives, and the effects of the T cell mitogens, concanavalin A, phytohemagglutinin, and staphylococcal entertoxin B (SEB) on the cyclic GMP content and guanylate cyclase activity of mouse splenic lymphocytes. Cyclic GMP and guanosine modestly increased the incorporation of [3H] thymidine into DNA by cultured lymphocytes, but were far less effective than their 8-Br-guanosine and 8-Br-5'-GMP exceeded that of 8-Br-cyclic GMP, when tested in the presence and absence of serum in the culture media. Combined addition of maximal doses of these nucleotides did not give additive stimulatory effects, suggesting an action on a common subpopulation of cells, and possibly a common mechanism. By contrast, cyclic AMP, 8-Br-cyclic AMP, 8-Br-adenosine, cholera toxin and prostaglandin E1 suppressed both basal [3H]thymidine incorporation and stimulation of this parameter by T-cell mitogens and the guanine nucleotides. Rapid effects of concanavalin A, phytohemagglutinin, SEB, guanosine, 5'-GMP, 8-Br-guanosine, and 8-Br-5'-GMP on the cyclic GMP content of murine lymphocytes could not be demonstrated. Similarly, concanavalin A, phytohemagglutinin and SEB failed to alter guanylate cyclase activity when added directly to cellular homogenates or pre-incubated with intact cells. Conversely, carbamylcholine rapidly increased lymphocyte cyclic GMP but was not mitogenic. These results are consistent with the hypothesis that cyclic GMP and cyclic AMP are antagonistic in their influence on lymphocyte mitogenesis. However, they also demonstrate that related nucleotides are more potent mitogens than cyclic GMP itself and suggest that activation of murine lymphocytes by concanavalin A, phytohemagglutinin and SEB may not be mediated by rapid increases in cellular cyclic GMP content. Since high concentrations of exogenous cyclic GMP and related nucleotides must be used to influence DNA synthesis, the biologic significance of this effect remains uncertain.", "contents": "Activation of murine lymphocytes by cyclic guanosine 3',5'-monophosphate: specificity and role in mitogen activity. Cyclic guanosine 3',5'-monophosphate (cyclic GMP) stimulates nucleic acid synthesis in lymphocytes, and has been implicated as the intracellular effector of the actions of mitogenic agents on these cells. In the present study, we examined the specificity of the mitogenic activity of cyclic GMP and of its 8-bromo (Br) derivatives, and the effects of the T cell mitogens, concanavalin A, phytohemagglutinin, and staphylococcal entertoxin B (SEB) on the cyclic GMP content and guanylate cyclase activity of mouse splenic lymphocytes. Cyclic GMP and guanosine modestly increased the incorporation of [3H] thymidine into DNA by cultured lymphocytes, but were far less effective than their 8-Br-guanosine and 8-Br-5'-GMP exceeded that of 8-Br-cyclic GMP, when tested in the presence and absence of serum in the culture media. Combined addition of maximal doses of these nucleotides did not give additive stimulatory effects, suggesting an action on a common subpopulation of cells, and possibly a common mechanism. By contrast, cyclic AMP, 8-Br-cyclic AMP, 8-Br-adenosine, cholera toxin and prostaglandin E1 suppressed both basal [3H]thymidine incorporation and stimulation of this parameter by T-cell mitogens and the guanine nucleotides. Rapid effects of concanavalin A, phytohemagglutinin, SEB, guanosine, 5'-GMP, 8-Br-guanosine, and 8-Br-5'-GMP on the cyclic GMP content of murine lymphocytes could not be demonstrated. Similarly, concanavalin A, phytohemagglutinin and SEB failed to alter guanylate cyclase activity when added directly to cellular homogenates or pre-incubated with intact cells. Conversely, carbamylcholine rapidly increased lymphocyte cyclic GMP but was not mitogenic. These results are consistent with the hypothesis that cyclic GMP and cyclic AMP are antagonistic in their influence on lymphocyte mitogenesis. However, they also demonstrate that related nucleotides are more potent mitogens than cyclic GMP itself and suggest that activation of murine lymphocytes by concanavalin A, phytohemagglutinin and SEB may not be mediated by rapid increases in cellular cyclic GMP content. Since high concentrations of exogenous cyclic GMP and related nucleotides must be used to influence DNA synthesis, the biologic significance of this effect remains uncertain."}
{"id": "PMID:4116", "title": "Characterization of protein kinases from bovine parotid glands. The effect of tolbutamide and its derivative on these partially purified enzymes.", "content": "1. Four fractions of protein kinase (EC 2.7.1.37) activity (Peak IH, IIH, IIIC and IVC) have been resolved and partially purified from the 100 000 X g supernatant fraction of bovine parotid glands by DEAE-cellulose and phosphocellulose chromatographies. 2. The protein kinases of Peak IH and IIH were adenosine 3',5'-monophosphate (cyclic AMP) -dependent and had similar enzymic properties. The enzyme activities of Peak IIIC and IVC were cyclic-AMP independent, but there were some distinct differences between their properties. The protein kinase in Peak IIIC was activated by 0.2 M NaCl or KCl and phosphorylated casein preferentially as the substrate, utilizing only ATP as a phosphate donor. On the other hand, the protein kinase in Peak IVC was inhibited by univalent salts and preferred phosvitin to casein, utilizing either ATP or GTP as a phosphate donor. 3. Tolbutamide increased the Km value for ATP and the dissociation constant for cyclic AMP, resulting in the inhibition of cyclic-AMP dependent protein kinase activity in the presence of cyclic AMP. Tolbtamide and its carboxy derivative, 1-butyl-3-p-carboxyphenylsulfonylurea, exerted almost no inhibitory effect on either the cyclic-AMP dependent protein kinase activities in the absence of cyclic AMP or on the cyclic-AMP independent protein kinase activities.", "contents": "Characterization of protein kinases from bovine parotid glands. The effect of tolbutamide and its derivative on these partially purified enzymes. 1. Four fractions of protein kinase (EC 2.7.1.37) activity (Peak IH, IIH, IIIC and IVC) have been resolved and partially purified from the 100 000 X g supernatant fraction of bovine parotid glands by DEAE-cellulose and phosphocellulose chromatographies. 2. The protein kinases of Peak IH and IIH were adenosine 3',5'-monophosphate (cyclic AMP) -dependent and had similar enzymic properties. The enzyme activities of Peak IIIC and IVC were cyclic-AMP independent, but there were some distinct differences between their properties. The protein kinase in Peak IIIC was activated by 0.2 M NaCl or KCl and phosphorylated casein preferentially as the substrate, utilizing only ATP as a phosphate donor. On the other hand, the protein kinase in Peak IVC was inhibited by univalent salts and preferred phosvitin to casein, utilizing either ATP or GTP as a phosphate donor. 3. Tolbutamide increased the Km value for ATP and the dissociation constant for cyclic AMP, resulting in the inhibition of cyclic-AMP dependent protein kinase activity in the presence of cyclic AMP. Tolbtamide and its carboxy derivative, 1-butyl-3-p-carboxyphenylsulfonylurea, exerted almost no inhibitory effect on either the cyclic-AMP dependent protein kinase activities in the absence of cyclic AMP or on the cyclic-AMP independent protein kinase activities."}
{"id": "PMID:4117", "title": "A study of the single polypeptide nature of rhodanese. A comparison of different preparations.", "content": "The enzyme rhodanese (EC 2.8.1.1) appears as a single polypeptide chain protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of this species is approx. 33 000. This contrasts with previous reports that rhodanese behaves on gel filtration chromatography as a rapidly equilibrating monomer-dimer system composed of identical subunits with a molecular weight of 18 500. We have investigated this apparent discrepancy by isolating the enzyme by the two different preparative procedures used in the above investigations. The two crystalline samples were subjected to gel filtration chromatography under a wide variety of conditions and to sodium dodecyl sulfate disc gel electrophoresis. The two preparations yielded rhodanese which behaved identically and no evidence for the monomeric species was obtained under any experimental condition tested. Thin-layer gel chromatography of clarified liver homogenates gave no evidence of rhodanese species other than that present in the purified samples. The variation in molecular weights observed in gel filtration chromatography may be a reflection of the conformational mobility of the enzyme leading to solvent-dependent changes in Stokes radius. If rhodanese is dimeric, special interactions must stabilize it under the conditions tested here.", "contents": "A study of the single polypeptide nature of rhodanese. A comparison of different preparations. The enzyme rhodanese (EC 2.8.1.1) appears as a single polypeptide chain protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of this species is approx. 33 000. This contrasts with previous reports that rhodanese behaves on gel filtration chromatography as a rapidly equilibrating monomer-dimer system composed of identical subunits with a molecular weight of 18 500. We have investigated this apparent discrepancy by isolating the enzyme by the two different preparative procedures used in the above investigations. The two crystalline samples were subjected to gel filtration chromatography under a wide variety of conditions and to sodium dodecyl sulfate disc gel electrophoresis. The two preparations yielded rhodanese which behaved identically and no evidence for the monomeric species was obtained under any experimental condition tested. Thin-layer gel chromatography of clarified liver homogenates gave no evidence of rhodanese species other than that present in the purified samples. The variation in molecular weights observed in gel filtration chromatography may be a reflection of the conformational mobility of the enzyme leading to solvent-dependent changes in Stokes radius. If rhodanese is dimeric, special interactions must stabilize it under the conditions tested here."}
{"id": "PMID:4118", "title": "Characterization of intracellular esterase A from Bacillus subtilis.", "content": "Esterase A (EC 3.1.1.1) obtained by sonic disruption of Bacillus subtilis SR22 (spoA12, trpC2) was purified approximately 400-fold by differential chemical and heating precipitation, DEAE-cellulose chromatography, and Bio-Rad P-150 gel filtration chromatography, with an overall yield of 59%. The purified enzyme hydrolyzed both aliphatic and aromatic acetate esters at substrate concentrations of 0.25 M but did not hydrolyze amino acid esters. Aliphatic alcohols did not inhibit the hydrolysis of p-nitrophenyl acetate; the most potent inhibitors of esterase activity were mercuric chloride, diisopropylfluorophosphate, eserine, and sodium fluoride.", "contents": "Characterization of intracellular esterase A from Bacillus subtilis. Esterase A (EC 3.1.1.1) obtained by sonic disruption of Bacillus subtilis SR22 (spoA12, trpC2) was purified approximately 400-fold by differential chemical and heating precipitation, DEAE-cellulose chromatography, and Bio-Rad P-150 gel filtration chromatography, with an overall yield of 59%. The purified enzyme hydrolyzed both aliphatic and aromatic acetate esters at substrate concentrations of 0.25 M but did not hydrolyze amino acid esters. Aliphatic alcohols did not inhibit the hydrolysis of p-nitrophenyl acetate; the most potent inhibitors of esterase activity were mercuric chloride, diisopropylfluorophosphate, eserine, and sodium fluoride."}
{"id": "PMID:4119", "title": "[Cow's milk alkaline phospharase. II. Subunit structure, metalloproteic nature and kinetic parameters (author's transl)].", "content": "Alkaline phosphatase (EC 3.1.3.1) from cow's milk as a dimer comprising two identical or very similar subunits of about 85 000 molecular weight. The enzyme contains 4.9 +/- 0.6 gatoms of zinc per mol of protein. The essential kinetic properties are the same as those of other alkaline phosphatases: variation of pH optimum value, the lack of specificity, increase of Km and V with pH value. The phosphotransferase activity is enlarged, at constant concentration of acceptor, with an increasing concentration of donor. The small size of molecules and the presence of hydroxyls and amino groups increase the percentage of transfer phosphate. The phosphotransferase reaction is better with the D-isomer of serine and the enzyme possesses a more important affinity for the D-phosphoserine.", "contents": "[Cow's milk alkaline phospharase. II. Subunit structure, metalloproteic nature and kinetic parameters (author's transl)]. Alkaline phosphatase (EC 3.1.3.1) from cow's milk as a dimer comprising two identical or very similar subunits of about 85 000 molecular weight. The enzyme contains 4.9 +/- 0.6 gatoms of zinc per mol of protein. The essential kinetic properties are the same as those of other alkaline phosphatases: variation of pH optimum value, the lack of specificity, increase of Km and V with pH value. The phosphotransferase activity is enlarged, at constant concentration of acceptor, with an increasing concentration of donor. The small size of molecules and the presence of hydroxyls and amino groups increase the percentage of transfer phosphate. The phosphotransferase reaction is better with the D-isomer of serine and the enzyme possesses a more important affinity for the D-phosphoserine."}
{"id": "PMID:4120", "title": "Kinetic properties of pulmonary angiotensin-converting enzyme. Hydrolysis of hippurylglycylglycine.", "content": "Some of the kinetic properties of angiotensin-converting enzyme (peptidyl-dipeptide hydrolase, EC 3.4.15.1) purified from hog lung have been determined using hippurylglycylglycine as substrate. The effects of pH and ionic environment on enzyme activity are complex and interdependent. At 0.1 M NaCl, the pH-activity curve shows an abrupt decrease in V/Km as the pH rises from 6 to 6.5, implying that ionization of a group in the enzyme with a pK in this range aids in binding of the substrate. Chloride is required for enzyme activity; there are two phases in the effect of NaCl. At both pH 6 AND 8, THE FIRST PHASE (UP TO 0.1 M NaCl) is activation. The second phase (above 0.1 M) at pH 6 is inhibition, while at pH 8 there is further activation which appears to be dependent upon ionic strength rather than a specific Cl-effect. Activation by cobalt and inhibition by EDTA are somewhat more effective at pH 6 than at pH 8. The nonapeptide inhibitor less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro is nearly equipotent at both pH 6 and 8, but Arg-Pro-Pro is more inhibitory at pH 8 than at pH 6.", "contents": "Kinetic properties of pulmonary angiotensin-converting enzyme. Hydrolysis of hippurylglycylglycine. Some of the kinetic properties of angiotensin-converting enzyme (peptidyl-dipeptide hydrolase, EC 3.4.15.1) purified from hog lung have been determined using hippurylglycylglycine as substrate. The effects of pH and ionic environment on enzyme activity are complex and interdependent. At 0.1 M NaCl, the pH-activity curve shows an abrupt decrease in V/Km as the pH rises from 6 to 6.5, implying that ionization of a group in the enzyme with a pK in this range aids in binding of the substrate. Chloride is required for enzyme activity; there are two phases in the effect of NaCl. At both pH 6 AND 8, THE FIRST PHASE (UP TO 0.1 M NaCl) is activation. The second phase (above 0.1 M) at pH 6 is inhibition, while at pH 8 there is further activation which appears to be dependent upon ionic strength rather than a specific Cl-effect. Activation by cobalt and inhibition by EDTA are somewhat more effective at pH 6 than at pH 8. The nonapeptide inhibitor less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro is nearly equipotent at both pH 6 and 8, but Arg-Pro-Pro is more inhibitory at pH 8 than at pH 6."}
{"id": "PMID:4121", "title": "Separation and properties of the NAD-linked and NADP-linked isozymes of succinic semialdehyde dehydrogenase in Euglena gracilis z.", "content": "Euglena gracilis z contained two succinic semialdehyde dehydrogenases (EC 1.2.1.16), one requiring NAD and the other NADP, and these isozymes were separated from each other and partially purified. The NAD-linked isozyme was relatively stable on storage at 5 degrees C whereas the NADP-linked one was extremely unstable unless 30% glycerol or ethyleneglycol was added. The optimum pH was 8.7 and optimum temperature 35-45 degrees C for both isozymes. They were inhibited by Zn2+ and activated, particularly the NAD-linked enzyme, by K+. Sulfhydryl reagents activated both isozymes. The Km values for succinic semialdehyde were 1.66 - 10(-4) M with the NAD-linked isozyme and 1.06 - 10(-3) M with the NADP-linked one. The NADP-linked isozyme was induced by glutamate while the NAD-linked one was not. Probable roles of these isozymes in the physiology of Euglena gracilis are discussed.", "contents": "Separation and properties of the NAD-linked and NADP-linked isozymes of succinic semialdehyde dehydrogenase in Euglena gracilis z. Euglena gracilis z contained two succinic semialdehyde dehydrogenases (EC 1.2.1.16), one requiring NAD and the other NADP, and these isozymes were separated from each other and partially purified. The NAD-linked isozyme was relatively stable on storage at 5 degrees C whereas the NADP-linked one was extremely unstable unless 30% glycerol or ethyleneglycol was added. The optimum pH was 8.7 and optimum temperature 35-45 degrees C for both isozymes. They were inhibited by Zn2+ and activated, particularly the NAD-linked enzyme, by K+. Sulfhydryl reagents activated both isozymes. The Km values for succinic semialdehyde were 1.66 - 10(-4) M with the NAD-linked isozyme and 1.06 - 10(-3) M with the NADP-linked one. The NADP-linked isozyme was induced by glutamate while the NAD-linked one was not. Probable roles of these isozymes in the physiology of Euglena gracilis are discussed."}
{"id": "PMID:4122", "title": "Activation of tyrosine hydroxylase by polyanions and salts. An electrostatic effect.", "content": "The activity of a partially purified preparation of tyrosine hydroxylase (EC 1.14.16.2) from the bovine caudate nucleus was increased by heparin, chondroitin sulfate, phosphatidylserine, polyacrylic acid, polyvinyl sulfuric acid and both poly-D-, and poly-L-glutamic acids, all polyanions. A variety of salts both activated the enzyme and prevented the activation by the polyanions. The observations that activity is increased when the enzyme interacts with salts and with macromolecules of high negative charge density are used to infer a model for these interactions and for the structural change in the enzyme that accompanies activation.", "contents": "Activation of tyrosine hydroxylase by polyanions and salts. An electrostatic effect. The activity of a partially purified preparation of tyrosine hydroxylase (EC 1.14.16.2) from the bovine caudate nucleus was increased by heparin, chondroitin sulfate, phosphatidylserine, polyacrylic acid, polyvinyl sulfuric acid and both poly-D-, and poly-L-glutamic acids, all polyanions. A variety of salts both activated the enzyme and prevented the activation by the polyanions. The observations that activity is increased when the enzyme interacts with salts and with macromolecules of high negative charge density are used to infer a model for these interactions and for the structural change in the enzyme that accompanies activation."}
{"id": "PMID:4123", "title": "Glycolipid glycosyl transferases of a hamster cell line in culture. I. Kinetic constants, substrate and donor nucleotide sugar specificities.", "content": "The properties of enzymes catalysing the transfer of a galactose from UDP-galactose to exogenous ceramide monohexoside and ceramide di-hexoside derived from the Syrian hamster cell line NIL 2 were studied. The products of these enzymes were characterized by chemical and enzymatic methods. Kinetic analyses showed that the enzymes are susceptible to inhibition and activation by a number of substrate analogues. The kinetic and inhibition constants, glycolipid substrate specificity and nucleotide sugar donor specificity have been studied.", "contents": "Glycolipid glycosyl transferases of a hamster cell line in culture. I. Kinetic constants, substrate and donor nucleotide sugar specificities. The properties of enzymes catalysing the transfer of a galactose from UDP-galactose to exogenous ceramide monohexoside and ceramide di-hexoside derived from the Syrian hamster cell line NIL 2 were studied. The products of these enzymes were characterized by chemical and enzymatic methods. Kinetic analyses showed that the enzymes are susceptible to inhibition and activation by a number of substrate analogues. The kinetic and inhibition constants, glycolipid substrate specificity and nucleotide sugar donor specificity have been studied."}
{"id": "PMID:4124", "title": "Pigeon liver diacetyl reductase. Effects of pH on the kinetic parameters of the reaction.", "content": "(1) The pH dependence of the kinetic parameters of the reaction catalyzed by pigeon liver diacetyl reductase (EC 1.1.1.5) was investigated in the pH range 5.1-8.6. (2) From the results obtained it is postulated that: (a), a group of pK around 7, active in the protonated form, participates in the interaction of the enzyme with NADH and NAD. (b), a second group with a pK of 8.4, active in the protonated form too, takes part in the binding of diacetyl to E-NADH. (c) A third group of pK about 4.7-5, active in the unprotonated form, is involved at least in the dissociation of the complex E-NAD and in the attachment of diacetyl to E-NADH.", "contents": "Pigeon liver diacetyl reductase. Effects of pH on the kinetic parameters of the reaction. (1) The pH dependence of the kinetic parameters of the reaction catalyzed by pigeon liver diacetyl reductase (EC 1.1.1.5) was investigated in the pH range 5.1-8.6. (2) From the results obtained it is postulated that: (a), a group of pK around 7, active in the protonated form, participates in the interaction of the enzyme with NADH and NAD. (b), a second group with a pK of 8.4, active in the protonated form too, takes part in the binding of diacetyl to E-NADH. (c) A third group of pK about 4.7-5, active in the unprotonated form, is involved at least in the dissociation of the complex E-NAD and in the attachment of diacetyl to E-NADH."}
{"id": "PMID:4125", "title": "Alkylation of cysteinyl residues of pig heart NAD-specific isocitrate dehydrogenase by iodoacetate.", "content": "Pig heart NAD-specific isocitrate dehydrogenase is inactivated by reaction with iodoacetate at pH 6.0. Loss of activity can be attributed to the formation of 1-2 mol of carboxymethyl-cysteine per peptide chain. The rate of inactivation is markedly decreased by the combined addition of Mn2+ and isocitrate, but not by alpha-ketoglutarate, the coenzyme NAD or the allosteric activator ADP. The substrate concentration dependence of the decreased rate of inactivation yields a dissociation constant of 1.6 mM for the enzyme-manganous-dibasic isocitrate complex, a value that is 50 times higher than the Km for this substrate. This result suggests that in protecting the enzyme against iodoacetate, isocitrate may bind to a region distinct from the catalytic site. Isocitrate and Mn2+ also prevent thermal denaturation, with an affinity for the enzyme close to that observed for the iodoacetate-sensitive site. The alkylatable cysteine residues may contribute to a manganous-isocitrate binding site which is responsible for stabilizing an active conformation of the enzyme.", "contents": "Alkylation of cysteinyl residues of pig heart NAD-specific isocitrate dehydrogenase by iodoacetate. Pig heart NAD-specific isocitrate dehydrogenase is inactivated by reaction with iodoacetate at pH 6.0. Loss of activity can be attributed to the formation of 1-2 mol of carboxymethyl-cysteine per peptide chain. The rate of inactivation is markedly decreased by the combined addition of Mn2+ and isocitrate, but not by alpha-ketoglutarate, the coenzyme NAD or the allosteric activator ADP. The substrate concentration dependence of the decreased rate of inactivation yields a dissociation constant of 1.6 mM for the enzyme-manganous-dibasic isocitrate complex, a value that is 50 times higher than the Km for this substrate. This result suggests that in protecting the enzyme against iodoacetate, isocitrate may bind to a region distinct from the catalytic site. Isocitrate and Mn2+ also prevent thermal denaturation, with an affinity for the enzyme close to that observed for the iodoacetate-sensitive site. The alkylatable cysteine residues may contribute to a manganous-isocitrate binding site which is responsible for stabilizing an active conformation of the enzyme."}
{"id": "PMID:4126", "title": "Purification and properties of NADP-dependent glutamate dehydrogenase from yeast nuclear fractions.", "content": "1. NADP-dependent glutamate dehydrogenase (EC 1.4.1.4) extracted from nuclear fractions of Saccharomyces cerevisiae was partially purified. The final purification achieved was over 100-fold over the initial extract. 2. Cellulose acetate electrophoresis shows that the preparation is close to homogeneity and that the enzyme is slightly more anionic than cytoplasmic glutamate dehydrogenase. 3. The response of the nuclear activity to variation of pH, of inorganic phosphate and other electrolyte concentration and of the concentration of the reaction substrates has been investigated. Several differences were detected in comparison with cytoplasmic glutamate dehydrogenase.", "contents": "Purification and properties of NADP-dependent glutamate dehydrogenase from yeast nuclear fractions. 1. NADP-dependent glutamate dehydrogenase (EC 1.4.1.4) extracted from nuclear fractions of Saccharomyces cerevisiae was partially purified. The final purification achieved was over 100-fold over the initial extract. 2. Cellulose acetate electrophoresis shows that the preparation is close to homogeneity and that the enzyme is slightly more anionic than cytoplasmic glutamate dehydrogenase. 3. The response of the nuclear activity to variation of pH, of inorganic phosphate and other electrolyte concentration and of the concentration of the reaction substrates has been investigated. Several differences were detected in comparison with cytoplasmic glutamate dehydrogenase."}
{"id": "PMID:4127", "title": "Comparative kinetic studies on the L-type pyruvate kinase from rat liver and the enzyme phosphorylated by cyclic 3', 5'-AMP-stimulated protein kinase.", "content": "The kinetics of rat liver L-type pyruvate kinase (EC 2.7.1.40), phosphorylated with cyclic AMP-stimulated protein kinase from the same source, and the unphosphorylated enzyme have been compared. The effects of pH and various concentrations of substrates, Mg2+, K+ and modifiers were studied. In the absence of fructose 1, 6-diphosphate at pH 7.3, the phosphorylated pyruvate kinase appeared to have a lower affinity for phosphoenolpyruvate (K0.5=0.8 mM) than the unphosphorylated enzyme (K0.5=0.3 mM). The enzyme activity vs. phosphoenolpyruvate concentration curve was more sigmoidal for the phosphorylated enzyme with a Hill coefficient of 2.6 compared to 1.6 for the unphosphorylated enzyme. Fructose 1, 6-diphosphate increased the apparent affinity of both enzyme forms for phosphoenolpyruvate. At saturating concentrations of this activator, the kinetics of both enzyme forms were transformed to approximately the same hyperbolic curve, with a Hill coefficient of 1.0 and K0.5 of about 0.04 mM for phosphoenolpyruvate. The apparent affinity of the enzyme for fructose 1, 6-diphosphate was high at 0.2 mM phosphoenolpyruvate with a K0.5=0.06 muM for the unphosphorylated pyruvate kinase and 0.13 muM for the phosphorylated enzyme. However, in the presence of 0.5 mM alanine plus 1.5 mM ATP, a higher fructose 1, 6-diphosphate concentration was needed for activation, with K0.5 of 0.4 muM for the unphosphorylated enzyme and of 1.4 muM for the phosphorylated enzyme. The results obtained strongly indicate that phosphorylation of pyruvate kinase may also inhibit the enzyme in vivo. Such an inhibition should be important during gluconeogenesis.", "contents": "Comparative kinetic studies on the L-type pyruvate kinase from rat liver and the enzyme phosphorylated by cyclic 3', 5'-AMP-stimulated protein kinase. The kinetics of rat liver L-type pyruvate kinase (EC 2.7.1.40), phosphorylated with cyclic AMP-stimulated protein kinase from the same source, and the unphosphorylated enzyme have been compared. The effects of pH and various concentrations of substrates, Mg2+, K+ and modifiers were studied. In the absence of fructose 1, 6-diphosphate at pH 7.3, the phosphorylated pyruvate kinase appeared to have a lower affinity for phosphoenolpyruvate (K0.5=0.8 mM) than the unphosphorylated enzyme (K0.5=0.3 mM). The enzyme activity vs. phosphoenolpyruvate concentration curve was more sigmoidal for the phosphorylated enzyme with a Hill coefficient of 2.6 compared to 1.6 for the unphosphorylated enzyme. Fructose 1, 6-diphosphate increased the apparent affinity of both enzyme forms for phosphoenolpyruvate. At saturating concentrations of this activator, the kinetics of both enzyme forms were transformed to approximately the same hyperbolic curve, with a Hill coefficient of 1.0 and K0.5 of about 0.04 mM for phosphoenolpyruvate. The apparent affinity of the enzyme for fructose 1, 6-diphosphate was high at 0.2 mM phosphoenolpyruvate with a K0.5=0.06 muM for the unphosphorylated pyruvate kinase and 0.13 muM for the phosphorylated enzyme. However, in the presence of 0.5 mM alanine plus 1.5 mM ATP, a higher fructose 1, 6-diphosphate concentration was needed for activation, with K0.5 of 0.4 muM for the unphosphorylated enzyme and of 1.4 muM for the phosphorylated enzyme. The results obtained strongly indicate that phosphorylation of pyruvate kinase may also inhibit the enzyme in vivo. Such an inhibition should be important during gluconeogenesis."}
{"id": "PMID:4128", "title": "Denaturation-induced disulfide formation in the enzyme rhodanese.", "content": "The effect of denaturants on the quantitation of free sulfhydryl groups in the enzyme rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) has been reinvestigated in some detail. The sulfhydryl assay with the colorimetric reagent 5, 5'-dithio-bis (2-nitrobenzoic acid) Nbs2 shows four sulfhydryl groups per enzyme molecule (mol. wt. 32 300) when the colorimetric reagent is added to the assay mixture before the denaturant, sodium dodecyl sulfate. On the other hand, only two sulfhydryl groups per molecule are observed when Nbs2 is added after denaturation has been initiated. The time dependence observed in this latter procedure indicates that the loss of the two groups is rapid and permanent. The results depend on the denaturant used: urea acts like sodium dodecyl sulfate while guanidine reveals four sulfhydryl groups independent of reagent order. The assay also gives four sulfhydryl groups independent of reagent order. The assay also gives four sulfhydryl groups independent of reagent order with urea or sodium dodecyl sulfate under conditions which are expected to limit metal ion-catalyzed oxidation of sulfhydryl groups (e.g. oxygen exclusion or metal ion chelation). Recent studies have shown that rhodanese has a molecular weight of 32 600, no disulfides and four sulfhydryl groups per molecule. These results together with the observations reported here are taken to indicate that a disulfide can be formed during denaturation of rhodanese and that the pathway of denaturation determines the result obtained.", "contents": "Denaturation-induced disulfide formation in the enzyme rhodanese. The effect of denaturants on the quantitation of free sulfhydryl groups in the enzyme rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) has been reinvestigated in some detail. The sulfhydryl assay with the colorimetric reagent 5, 5'-dithio-bis (2-nitrobenzoic acid) Nbs2 shows four sulfhydryl groups per enzyme molecule (mol. wt. 32 300) when the colorimetric reagent is added to the assay mixture before the denaturant, sodium dodecyl sulfate. On the other hand, only two sulfhydryl groups per molecule are observed when Nbs2 is added after denaturation has been initiated. The time dependence observed in this latter procedure indicates that the loss of the two groups is rapid and permanent. The results depend on the denaturant used: urea acts like sodium dodecyl sulfate while guanidine reveals four sulfhydryl groups independent of reagent order. The assay also gives four sulfhydryl groups independent of reagent order. The assay also gives four sulfhydryl groups independent of reagent order with urea or sodium dodecyl sulfate under conditions which are expected to limit metal ion-catalyzed oxidation of sulfhydryl groups (e.g. oxygen exclusion or metal ion chelation). Recent studies have shown that rhodanese has a molecular weight of 32 600, no disulfides and four sulfhydryl groups per molecule. These results together with the observations reported here are taken to indicate that a disulfide can be formed during denaturation of rhodanese and that the pathway of denaturation determines the result obtained."}
{"id": "PMID:4129", "title": "Studies on a 3beta-hydroxysteroid sulphotransferase from rat liver.", "content": "A steroid sulphotransferase (EC 2.8.2.2) was partially purified from female rat liver. The enzyme was active towards the substrates, dehydroepiandrosterone, epiandrosterone and pregnenolone but was inactive towards oestrogens, cholesterol and ergocalciferol. A pH optimum of 5.0 was recorded but the enzyme was unstable at low pH. The enzyme was stimulated slightly by the addition of reducing agents and inhibited by p-chloromercuribenzoate and HgCl2. Crude enzyme activity was markedly stimulated by divalent cations but this effect was not observed with purified enzyme. A Km of 13 muM was calculated for the donor substrate 3'-phosphoadenylyl sulphate and the acceptor substrate, dehydroepiandrosterone had a Km value of 6 muM. The enzyme appeared to be highly susceptible to product inhibition by adenosine 3', 5'-diphosphate.", "contents": "Studies on a 3beta-hydroxysteroid sulphotransferase from rat liver. A steroid sulphotransferase (EC 2.8.2.2) was partially purified from female rat liver. The enzyme was active towards the substrates, dehydroepiandrosterone, epiandrosterone and pregnenolone but was inactive towards oestrogens, cholesterol and ergocalciferol. A pH optimum of 5.0 was recorded but the enzyme was unstable at low pH. The enzyme was stimulated slightly by the addition of reducing agents and inhibited by p-chloromercuribenzoate and HgCl2. Crude enzyme activity was markedly stimulated by divalent cations but this effect was not observed with purified enzyme. A Km of 13 muM was calculated for the donor substrate 3'-phosphoadenylyl sulphate and the acceptor substrate, dehydroepiandrosterone had a Km value of 6 muM. The enzyme appeared to be highly susceptible to product inhibition by adenosine 3', 5'-diphosphate."}
{"id": "PMID:4130", "title": "An ESR study of the influence of some physico-chemical factors on the conformation of a postsynaptic acetylcholinesterase.", "content": "1. In a previous ESR study of a membrane acetylcholinesterase (EC 3.1.1.7) we found, contrary to observations by other authors, spectra indicating that the active serine might be located in a pocket of the enzyme surface. In order to inquire into this possibility, ESR spectra were studied under the influence of different physico-chemical factors known to cause an unfolding of proteins. 2. The active serine of the postsynaptic membrane acetylcholinesterase of Torpedo marmorata electric organ was spin labeled using 1-oxyl-2, 2, 6, 6-tetramethyl-4-piperidinyletoxyphosphonofluoridate. 3. The effect of the chosen physico-chemical factors was an increase in the rotational freedom of spin labels; this result corroborates the suggestion that the active center of our acetylcholinesterase preparation is located in a pocket.", "contents": "An ESR study of the influence of some physico-chemical factors on the conformation of a postsynaptic acetylcholinesterase. 1. In a previous ESR study of a membrane acetylcholinesterase (EC 3.1.1.7) we found, contrary to observations by other authors, spectra indicating that the active serine might be located in a pocket of the enzyme surface. In order to inquire into this possibility, ESR spectra were studied under the influence of different physico-chemical factors known to cause an unfolding of proteins. 2. The active serine of the postsynaptic membrane acetylcholinesterase of Torpedo marmorata electric organ was spin labeled using 1-oxyl-2, 2, 6, 6-tetramethyl-4-piperidinyletoxyphosphonofluoridate. 3. The effect of the chosen physico-chemical factors was an increase in the rotational freedom of spin labels; this result corroborates the suggestion that the active center of our acetylcholinesterase preparation is located in a pocket."}
{"id": "PMID:4131", "title": "Presence and androgen control of an alkaline phosphatase in the nucleus of rat ventral prostate.", "content": "The presence of alkaline phosphatase (EC 3.1.3.1) activity has been demonstrated in nuclei of rat ventral prostate. This enzyme activity remained after washing of isolated nuclei with 0.5% Triton X-100; an acid phosphatase initially present with the nuclear fraction was removed by this treatment. The nuclear alkaline phosphatase, examined by utilizing p-nitrophenyl phosphate as substrate, had a pH optimum of 9.5-10.3, and a broad substrate specificity: p-nitrophenyl phosphate greater than phosphothreonine greater than beta-glycerophosphate greater than phosphoserine. The nuclear phosphatase was sensitive to denaturation by heat or urea treatments and was also inhibited by Pi, L-phenylalanine, homoarginine, dithiothreitol, and EDTA. The EDTA-inhibited enzyme was maximally reactivated by Zn2+, although Mg2+, or Ca2+ were also effective at somewhat higher concentrations. Orchiectomy of adult rats resulted in an increase in the nuclear alkaline phosphatase activity (2-3-fold at 24 or 48 h postorchiectomy). A decline in the protein: DNA ratio also occurred following orchiectomy, but the increase in phosphatase specific activity was evident whether expressed per unit of protein or per unit of DNA. Testosterone replacement following orchiectomy abolished the increase in nuclear phosphatase activity. The results suggest that the prostatic nuclear alkaline phosphatase may be involved in events related to inactivation of the prostate nucleus following androgen deprivation.", "contents": "Presence and androgen control of an alkaline phosphatase in the nucleus of rat ventral prostate. The presence of alkaline phosphatase (EC 3.1.3.1) activity has been demonstrated in nuclei of rat ventral prostate. This enzyme activity remained after washing of isolated nuclei with 0.5% Triton X-100; an acid phosphatase initially present with the nuclear fraction was removed by this treatment. The nuclear alkaline phosphatase, examined by utilizing p-nitrophenyl phosphate as substrate, had a pH optimum of 9.5-10.3, and a broad substrate specificity: p-nitrophenyl phosphate greater than phosphothreonine greater than beta-glycerophosphate greater than phosphoserine. The nuclear phosphatase was sensitive to denaturation by heat or urea treatments and was also inhibited by Pi, L-phenylalanine, homoarginine, dithiothreitol, and EDTA. The EDTA-inhibited enzyme was maximally reactivated by Zn2+, although Mg2+, or Ca2+ were also effective at somewhat higher concentrations. Orchiectomy of adult rats resulted in an increase in the nuclear alkaline phosphatase activity (2-3-fold at 24 or 48 h postorchiectomy). A decline in the protein: DNA ratio also occurred following orchiectomy, but the increase in phosphatase specific activity was evident whether expressed per unit of protein or per unit of DNA. Testosterone replacement following orchiectomy abolished the increase in nuclear phosphatase activity. The results suggest that the prostatic nuclear alkaline phosphatase may be involved in events related to inactivation of the prostate nucleus following androgen deprivation."}
{"id": "PMID:4132", "title": "Removal of phosphate groups from casein with potato acid phosphatase.", "content": "Potato acid phosphatase (EC 3.1.3.2) was used to remove the eight phosphate groups from alphas1-casein. Unlike most acid phosphatases, which are active at pH 6.0 or below, potato acid phosphatase can catalyze the dephosphorylation of alphas1-casein at pH 7.0. Although phosphate inhibition is considerable (K1=0.42 mM phosphate), the phosphate ions produced by the dephosphorylation of casein can be removed by dialysis, allowing the reaction to go to completion. The dephosphorylated alphas1-casein is homogeneous on gel electrophoresis with a slower mobility than native alphas1-casein and has an amino acid composition which is identical to native alphas1-casein. Thus the removal of phosphate groups from casein does not alter its primary structure. Potato acid phosphatase also removed the phosphate groups from other phosphoproteins, such as beta-casein, riboflavin binding protein, pepsinogen, ovalbumin, and phosvitin.", "contents": "Removal of phosphate groups from casein with potato acid phosphatase. Potato acid phosphatase (EC 3.1.3.2) was used to remove the eight phosphate groups from alphas1-casein. Unlike most acid phosphatases, which are active at pH 6.0 or below, potato acid phosphatase can catalyze the dephosphorylation of alphas1-casein at pH 7.0. Although phosphate inhibition is considerable (K1=0.42 mM phosphate), the phosphate ions produced by the dephosphorylation of casein can be removed by dialysis, allowing the reaction to go to completion. The dephosphorylated alphas1-casein is homogeneous on gel electrophoresis with a slower mobility than native alphas1-casein and has an amino acid composition which is identical to native alphas1-casein. Thus the removal of phosphate groups from casein does not alter its primary structure. Potato acid phosphatase also removed the phosphate groups from other phosphoproteins, such as beta-casein, riboflavin binding protein, pepsinogen, ovalbumin, and phosvitin."}
{"id": "PMID:4133", "title": "Multiple forms of cyclic nucleotide phosphodiesterase in pig epidermis.", "content": "Pig epidermal cyclic nucleotide phosphodiesterases (EC 3.1.4.16) have been partially purified by DEAE-cellulose column chromatography. At least three different forms of the epidermal phosphodiesterases were identified. They were cyclic GMP-specific, cyclic GMP- and cyclic AMP-hydrolyzing and apparently a cyclic AMP-specific enzyme: the first two forms were soluble and the last was the particulate enzyme. The cyclic GMP-specific soluble fraction had a relatively low Km, the cyclic GMP- and cyclic AMP-hydrolyzing fraction had a high Km for the respective substrates and the third particulate enzyme had both high and low Km values for cyclic AMP. The cyclic GMP-hydrolyzing enzyme was localized almost entirely in the soluble fraction, whereas cyclic AMP-hydrolyzing enzyme was distributed to both soluble and particulate fractions. Thus, our studies show that the multiple forms of pig epidermal enzyme differ distinctly in their substrate affinity, specificity and subcellular distribution.", "contents": "Multiple forms of cyclic nucleotide phosphodiesterase in pig epidermis. Pig epidermal cyclic nucleotide phosphodiesterases (EC 3.1.4.16) have been partially purified by DEAE-cellulose column chromatography. At least three different forms of the epidermal phosphodiesterases were identified. They were cyclic GMP-specific, cyclic GMP- and cyclic AMP-hydrolyzing and apparently a cyclic AMP-specific enzyme: the first two forms were soluble and the last was the particulate enzyme. The cyclic GMP-specific soluble fraction had a relatively low Km, the cyclic GMP- and cyclic AMP-hydrolyzing fraction had a high Km for the respective substrates and the third particulate enzyme had both high and low Km values for cyclic AMP. The cyclic GMP-hydrolyzing enzyme was localized almost entirely in the soluble fraction, whereas cyclic AMP-hydrolyzing enzyme was distributed to both soluble and particulate fractions. Thus, our studies show that the multiple forms of pig epidermal enzyme differ distinctly in their substrate affinity, specificity and subcellular distribution."}
{"id": "PMID:4134", "title": "Ascorbic acid-2-sulfate sulfhohydrolase activity of human arylsulfatase A.", "content": "Pure human arylsulfatase A (EC 3.1.6.1) was found to hydrolyze ascorbic acid 2-sulfate to ascorbic acid and inorganic sulfate at rates from 200 to 2000 mumol/mg per h depending on the method of assay. This rate was lower than that observed with the synthetic substrate 4-nitrocatechol sulfate, but higher than that seen with the physiological substrate cerebroside sulfate. Extracts of cultured fibroblasts from normal subjects were also shown to hydrolyze ascorbic acid 2-sulfate; extracts of fibroblasts from patients with metachromatic leukodystrophy, known to be deficient in arylsulfatase A, did not. Similarly, hydrolysis of ascorbic acid 2-sulfate was not observed when a partially purified preparation of human arylsulfatase B was tested under a variety of conditions. Thus, in the human, arylsulfatase A appears to be the major, if not the only, ascorbic acid-2-sulfate sulfohydrolase.", "contents": "Ascorbic acid-2-sulfate sulfhohydrolase activity of human arylsulfatase A. Pure human arylsulfatase A (EC 3.1.6.1) was found to hydrolyze ascorbic acid 2-sulfate to ascorbic acid and inorganic sulfate at rates from 200 to 2000 mumol/mg per h depending on the method of assay. This rate was lower than that observed with the synthetic substrate 4-nitrocatechol sulfate, but higher than that seen with the physiological substrate cerebroside sulfate. Extracts of cultured fibroblasts from normal subjects were also shown to hydrolyze ascorbic acid 2-sulfate; extracts of fibroblasts from patients with metachromatic leukodystrophy, known to be deficient in arylsulfatase A, did not. Similarly, hydrolysis of ascorbic acid 2-sulfate was not observed when a partially purified preparation of human arylsulfatase B was tested under a variety of conditions. Thus, in the human, arylsulfatase A appears to be the major, if not the only, ascorbic acid-2-sulfate sulfohydrolase."}
{"id": "PMID:4135", "title": "Human alpha-fucosidase. Single residual enzymatic form in fucosidosis.", "content": "Four major forms of alpha-fucosidase (EC 3.2.1.51) activity were separated by isoelectrofocusing from sera of normal control individuals. All forms shifted towards less acidic pI values after neuraminidase treatment. In two patients affected with fucosidosis, only a single major acidic peak was observed and this was affected to a lesser degree by neuraminidase treatment. The kinetics of heat inactivation of the residual activity found in these two patients showed two decay rates while the controls showed only one rate. These data are considered in relation to the hypothesis of the existence of interconvertible thermolabile and thermostable forms of the enzyme which has been discussed in the preceeding paper. The residual alpha-fucosidase found in patients could be structurally altered so that its ability to form the thermostable higher molecular weight aggregates is impaired.", "contents": "Human alpha-fucosidase. Single residual enzymatic form in fucosidosis. Four major forms of alpha-fucosidase (EC 3.2.1.51) activity were separated by isoelectrofocusing from sera of normal control individuals. All forms shifted towards less acidic pI values after neuraminidase treatment. In two patients affected with fucosidosis, only a single major acidic peak was observed and this was affected to a lesser degree by neuraminidase treatment. The kinetics of heat inactivation of the residual activity found in these two patients showed two decay rates while the controls showed only one rate. These data are considered in relation to the hypothesis of the existence of interconvertible thermolabile and thermostable forms of the enzyme which has been discussed in the preceeding paper. The residual alpha-fucosidase found in patients could be structurally altered so that its ability to form the thermostable higher molecular weight aggregates is impaired."}
{"id": "PMID:4136", "title": "Separation of two PZ-peptidases from bovine dental follicle.", "content": "Two PZ-peptidases (EC 3.4.-) (A and B) cleaving a synthetic substrate for collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (PZ-peptide) have been separated from the particulate fraction of bovine dental follicle. PZ-peptidase A had a molecular weight of 220 000, an optimum pH at 8.0-8.5, and a Km value of 67 muM toward PZ-peptide at pH 7.1, whereas PZ-peptidase B had a molecular weight of 20 000, an optimum pH at 6.5-6.7, and a Km value of 400 muM toward PZ-peptide at pH 7.1. Two similar enzymes were also isolated from the soluble fraction. Since the pH-activity curve of the crude tissue preparations such as homogenate, microsomes and soluble supernatant had two peaks at 6.5-6.7 and 8.0-8.5, both PZ-peptidase A and B may exist in situ as two independent active enzymes.", "contents": "Separation of two PZ-peptidases from bovine dental follicle. Two PZ-peptidases (EC 3.4.-) (A and B) cleaving a synthetic substrate for collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (PZ-peptide) have been separated from the particulate fraction of bovine dental follicle. PZ-peptidase A had a molecular weight of 220 000, an optimum pH at 8.0-8.5, and a Km value of 67 muM toward PZ-peptide at pH 7.1, whereas PZ-peptidase B had a molecular weight of 20 000, an optimum pH at 6.5-6.7, and a Km value of 400 muM toward PZ-peptide at pH 7.1. Two similar enzymes were also isolated from the soluble fraction. Since the pH-activity curve of the crude tissue preparations such as homogenate, microsomes and soluble supernatant had two peaks at 6.5-6.7 and 8.0-8.5, both PZ-peptidase A and B may exist in situ as two independent active enzymes."}
{"id": "PMID:4137", "title": "Properties of the major carboxypeptidase in the larvae of the webbing clothes moth, Tineola bisselliella.", "content": "The larvae of the webbing clothes moth, Tineola bisselliella contain two carboxypeptidases (EC 3.4.12-) and one of these has been purified by preparative polyacrylamide gel electrophoresis. Its pH optimum for the hydrolysis of N-benzyloxycarbonyl-glycyl-leucine was pH 7.5-7.7 and its molecular weight as judged by gel filtration was 72 000. It is strongly inhibited by disopropylfluorophosphate, thiol reagents and some metal cations and also by 1:10 phenanthroline but not EDTA. Km and V values for the hydrolysis of 13 N-acyl dipeptides were determined. The enzyme has a strong preference for neutral aliphatic amino acid residues and does not hydrolyse C-terminal proline, arginine or lysine. It is a true carboxypeptidase, requiring an L-amino acid in the C-terminal position, with a free carboxyl group and hydrolysing peptide substrates consecutively from the C-terminal end. Dipeptides are cleaved much more slosly than tripeptides or N-acyl dipeptides.", "contents": "Properties of the major carboxypeptidase in the larvae of the webbing clothes moth, Tineola bisselliella. The larvae of the webbing clothes moth, Tineola bisselliella contain two carboxypeptidases (EC 3.4.12-) and one of these has been purified by preparative polyacrylamide gel electrophoresis. Its pH optimum for the hydrolysis of N-benzyloxycarbonyl-glycyl-leucine was pH 7.5-7.7 and its molecular weight as judged by gel filtration was 72 000. It is strongly inhibited by disopropylfluorophosphate, thiol reagents and some metal cations and also by 1:10 phenanthroline but not EDTA. Km and V values for the hydrolysis of 13 N-acyl dipeptides were determined. The enzyme has a strong preference for neutral aliphatic amino acid residues and does not hydrolyse C-terminal proline, arginine or lysine. It is a true carboxypeptidase, requiring an L-amino acid in the C-terminal position, with a free carboxyl group and hydrolysing peptide substrates consecutively from the C-terminal end. Dipeptides are cleaved much more slosly than tripeptides or N-acyl dipeptides."}
{"id": "PMID:4138", "title": "Cathepsins B1 from human fetal membranes.", "content": "Cathepsins B1 (EC 3.4.22.1) were isolated from fetal membranes of human placenta, i.e. amnion and chorion-decidua. Purification of the enzymes was achieved by the freezing-thawing technique, ammonium sulphate fractionation and Sephadex gel filtration. Cathepsis B1 separated either from amnion or from chorion-decidua exhibited optimum activity at pH 6.2, and an optimum temperature between 42-45 degrees C. They were inhibited by heavy metals, and compounds which react with the thiol groups. Isoelectric focusing demonstrated three isoenzymes of cathepsin B1 originating from chorion-decidua, while only one band was found for the enzyme from amnion.", "contents": "Cathepsins B1 from human fetal membranes. Cathepsins B1 (EC 3.4.22.1) were isolated from fetal membranes of human placenta, i.e. amnion and chorion-decidua. Purification of the enzymes was achieved by the freezing-thawing technique, ammonium sulphate fractionation and Sephadex gel filtration. Cathepsis B1 separated either from amnion or from chorion-decidua exhibited optimum activity at pH 6.2, and an optimum temperature between 42-45 degrees C. They were inhibited by heavy metals, and compounds which react with the thiol groups. Isoelectric focusing demonstrated three isoenzymes of cathepsin B1 originating from chorion-decidua, while only one band was found for the enzyme from amnion."}
{"id": "PMID:4139", "title": "Purification of multiple forms of adenosine deaminase from rabbit intestine.", "content": "Two forms of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), differing in molecular size, have been purified and obtained in homogeneous form from rabbit intestine. The purification procedures involved extraction with acetate buffer, pH 5.5, precipitation and fractional reextraction with (NH4)2SO4, ion-exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-75 and Sephadex G-200. Gel filtrations analysis gave molecular weight estimates of 265 000 and 32 000 for the large and small deaminases respectively. The two enzymes forms had similar pH optima and pH stability ranges.", "contents": "Purification of multiple forms of adenosine deaminase from rabbit intestine. Two forms of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), differing in molecular size, have been purified and obtained in homogeneous form from rabbit intestine. The purification procedures involved extraction with acetate buffer, pH 5.5, precipitation and fractional reextraction with (NH4)2SO4, ion-exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-75 and Sephadex G-200. Gel filtrations analysis gave molecular weight estimates of 265 000 and 32 000 for the large and small deaminases respectively. The two enzymes forms had similar pH optima and pH stability ranges."}
{"id": "PMID:4140", "title": "Stimulation of photosystem I-induced oxidation of chloroplast cytochrome b-559 by pre-illumination and by low pH.", "content": "(1) The proportion of higher plant chloroplast cytochrome b-559 oxidizable during illumination by low intensity 732 nm light increases as the pH is decreased below 6.5. At pH 5.0-5.3 total oxidation is seen and subsequent red light can cause reduction of up to 2/3 of the oxidized cytochrome. The oxidation by far red light at pH 5 is inhibited by 2 muM 2,5-dibromo-3-methyl-6-isopropyl-rho-benzoquinone whereas the red light-induced reduction is inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea. In this pH range ferricyanide-oxidized cytochrome b-559 exists in a form not reducible by ferrocyanide. (2) An increase in the amplitude of far-red induced oxidation also occurs at higher pH (up to pH 7.8) after pre-treatment of chloroplasts with substantially higher levels of light (approx. 10(6) ergs-cm-2-s-1). The degree of light activation is pH dependent, being more pronounced at lower pH. After light activation, cytochrome b-559 can be completely oxidized by far-red light in a manner reversible by red light up to pH values of 6, and the curve describing the amplitude of far-red oxidation as a function of pH is shifted by 0.5-1.0 pH unit toward higher pH. Far-red oxidation and red light reduction are again inhibited by 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone and 3-(3,4-dichlorophenyl)-1,1-dimethylurea, respectively. (3) Light activation at pH 5.2-6.0 is also manifested in a small decrease in the amplitude of subsequent dark ferrocyanide reduction, and this decrease is inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (10 muM). (4) The effect of intramembranal acidity on the effective redox potential of cytochrome b-559 and its function is discussed.", "contents": "Stimulation of photosystem I-induced oxidation of chloroplast cytochrome b-559 by pre-illumination and by low pH. (1) The proportion of higher plant chloroplast cytochrome b-559 oxidizable during illumination by low intensity 732 nm light increases as the pH is decreased below 6.5. At pH 5.0-5.3 total oxidation is seen and subsequent red light can cause reduction of up to 2/3 of the oxidized cytochrome. The oxidation by far red light at pH 5 is inhibited by 2 muM 2,5-dibromo-3-methyl-6-isopropyl-rho-benzoquinone whereas the red light-induced reduction is inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea. In this pH range ferricyanide-oxidized cytochrome b-559 exists in a form not reducible by ferrocyanide. (2) An increase in the amplitude of far-red induced oxidation also occurs at higher pH (up to pH 7.8) after pre-treatment of chloroplasts with substantially higher levels of light (approx. 10(6) ergs-cm-2-s-1). The degree of light activation is pH dependent, being more pronounced at lower pH. After light activation, cytochrome b-559 can be completely oxidized by far-red light in a manner reversible by red light up to pH values of 6, and the curve describing the amplitude of far-red oxidation as a function of pH is shifted by 0.5-1.0 pH unit toward higher pH. Far-red oxidation and red light reduction are again inhibited by 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone and 3-(3,4-dichlorophenyl)-1,1-dimethylurea, respectively. (3) Light activation at pH 5.2-6.0 is also manifested in a small decrease in the amplitude of subsequent dark ferrocyanide reduction, and this decrease is inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (10 muM). (4) The effect of intramembranal acidity on the effective redox potential of cytochrome b-559 and its function is discussed."}
{"id": "PMID:4141", "title": "The effect of formate on cytochrome aa3 and on electron transport in the intact respiratory chain.", "content": "1. Formate inhibits cytochrome c oxidase activity both in intact mitochondria and submitochondrial particles, and in isolated cytochrome aa3. The inhibition increases with decreasing pH, indicating that HCOOH may be the inhibitory species. 2. Formate induces a blue shift in the absorption spectrum of oxidized cytochrome aa3 (a3 + a33+) and in the half-reduced species (a2 + a33+). Comparison with cyanide-induced spectral shifts, towards the red, indicates that formate and cyanide have opposite effects on the aa3 spectrum, both in the fully oxidized and the half-reduced states. The formate spectra provide a new method of obtaining the difference spectrum of a32+ minus a33+, free of the difficulties with cyanide (which induces marked high leads to low spin spectral shifts in cytochrome a33+) and azide (which induces peak shifts of cytochrome a2+ towards the blue in both alpha- and Soret regions). 3. The rate of formate dissociation from cytochrome a2+ a33+ -HCOOH is faster than its rate of dissociation from a3+ a33+ -HCOOH, especially in the presence of cytochrome c. The Ki for formate inhibition of respiration is a function of the reduction state of the system, varying from 30 mM (100% reduction) to 1 mM (100% oxidation) at pH 7.4, 30 degrees C. 4. Succinate-cytochrome c reductase activity is also inhibited by formate, in a reaction competitive with succinate and dependent on [formate]2. 5. Formate inhibition of ascorbate plus N, N, N', N'-tetramethyl-p-phenylenediamine oxidation by intact rat liver mitochondria is partially released by uncoupler addition. Formate is permeable through the inner mitochondrial membrane and no differences in 'on' or 'off' inhibition rates were observed when intact mitochondria were compared with submitochondrial particles. 6. NADH-cytochrome c reductase activity is unaffected by formate in submitochondrial particles, but mitochondrial oxidation of glutamate plus malate is subject both to terminal inhibition at the cytochrome aa3 level and to a slow extra inhibition by formate following uncoupler addition, indicating a third site of formate action in the intact mitochondrion.", "contents": "The effect of formate on cytochrome aa3 and on electron transport in the intact respiratory chain. 1. Formate inhibits cytochrome c oxidase activity both in intact mitochondria and submitochondrial particles, and in isolated cytochrome aa3. The inhibition increases with decreasing pH, indicating that HCOOH may be the inhibitory species. 2. Formate induces a blue shift in the absorption spectrum of oxidized cytochrome aa3 (a3 + a33+) and in the half-reduced species (a2 + a33+). Comparison with cyanide-induced spectral shifts, towards the red, indicates that formate and cyanide have opposite effects on the aa3 spectrum, both in the fully oxidized and the half-reduced states. The formate spectra provide a new method of obtaining the difference spectrum of a32+ minus a33+, free of the difficulties with cyanide (which induces marked high leads to low spin spectral shifts in cytochrome a33+) and azide (which induces peak shifts of cytochrome a2+ towards the blue in both alpha- and Soret regions). 3. The rate of formate dissociation from cytochrome a2+ a33+ -HCOOH is faster than its rate of dissociation from a3+ a33+ -HCOOH, especially in the presence of cytochrome c. The Ki for formate inhibition of respiration is a function of the reduction state of the system, varying from 30 mM (100% reduction) to 1 mM (100% oxidation) at pH 7.4, 30 degrees C. 4. Succinate-cytochrome c reductase activity is also inhibited by formate, in a reaction competitive with succinate and dependent on [formate]2. 5. Formate inhibition of ascorbate plus N, N, N', N'-tetramethyl-p-phenylenediamine oxidation by intact rat liver mitochondria is partially released by uncoupler addition. Formate is permeable through the inner mitochondrial membrane and no differences in 'on' or 'off' inhibition rates were observed when intact mitochondria were compared with submitochondrial particles. 6. NADH-cytochrome c reductase activity is unaffected by formate in submitochondrial particles, but mitochondrial oxidation of glutamate plus malate is subject both to terminal inhibition at the cytochrome aa3 level and to a slow extra inhibition by formate following uncoupler addition, indicating a third site of formate action in the intact mitochondrion."}
{"id": "PMID:4142", "title": "The coupling factor of photophosphorylation and the electric properties of the thylakoid membrane.", "content": "The rate of ATP synthesis of illuminated chloroplasts is correlated with the electric conductance of their inner membranes. In agreement with previous studies it is shown that ATP synthesis is paralleled by an increased conductance of the thylakoid membrane. This conductance together with the ability to form ATP is abolished if chloroplasts are treated with an antibody against the coupling factor CF1. It is not influenced by the fragmented monovalent antibody. This parallels the lack of influence of the fragmented antibody on ATP synthesis in contrast to its influence on hydrolysis and exchange reactions. We conclude that there are different sites for the interaction of the coupling factor with adenine nucleotides. Extraction of the coupling factor is shown to increase the membrane conductance by more than two orders of magnitude. Reincorporation of the crude coupling factor partially restores the net conductance of the membrane (increase in resistance by a factor of 2.5), while a higher degree of restoration was observed for ATP synthesis and the proton conductivity of the membrane. We conclude that the extraction procedure opens different conductive channels in the membrane; a proton specific one, possibly associated with the binding protein for the coupling factor, plus other channels for \"non-protons\" which in contrast to the proton channel cannot be plugged by reincorporation of the coupling factor.", "contents": "The coupling factor of photophosphorylation and the electric properties of the thylakoid membrane. The rate of ATP synthesis of illuminated chloroplasts is correlated with the electric conductance of their inner membranes. In agreement with previous studies it is shown that ATP synthesis is paralleled by an increased conductance of the thylakoid membrane. This conductance together with the ability to form ATP is abolished if chloroplasts are treated with an antibody against the coupling factor CF1. It is not influenced by the fragmented monovalent antibody. This parallels the lack of influence of the fragmented antibody on ATP synthesis in contrast to its influence on hydrolysis and exchange reactions. We conclude that there are different sites for the interaction of the coupling factor with adenine nucleotides. Extraction of the coupling factor is shown to increase the membrane conductance by more than two orders of magnitude. Reincorporation of the crude coupling factor partially restores the net conductance of the membrane (increase in resistance by a factor of 2.5), while a higher degree of restoration was observed for ATP synthesis and the proton conductivity of the membrane. We conclude that the extraction procedure opens different conductive channels in the membrane; a proton specific one, possibly associated with the binding protein for the coupling factor, plus other channels for \"non-protons\" which in contrast to the proton channel cannot be plugged by reincorporation of the coupling factor."}
{"id": "PMID:4143", "title": "Evidence against proton gradient formation being the cause of chlorophyll fluorescence quenching by N-methylphenazonium methosulfate.", "content": "In strong illumination, 3-(3, 4-dichlorophenyl)-1,1-dimethylurea (DCMU)-poisoned chloroplasts exhibit a high yield of chlorophyll fluorescence while P-700 turnover, proton uptake, and phosphorylation are inhibited and a pH gradient is undectectable. When 10muM N-methylphenazonium methosulfate (PMS) is included, the fluorescence yield in light is substantially reduced, and when 100 muM ascorbate is also included, the yield is diminished approximately to the level in darkness. Only very slight increases in P-700 turnover and proton uptake (but no detectable pH gradient) accompany the fluorescence yield decline. When 10muM PMS and 15 mM ascorbate are added to poisoned chloroplasts (the oxygen concentration being greatly reduced), P-700 turnover, proton uptake, the pH gradient and phosphorylation all reach high levels. In this case, the yield of chlorophyll fluorescence is low and is the same in both light and dark. Further addition of an uncoupler eliminates proton uptake, the pH gradient and phosphorylation but does not significantly elevate the fluorescence yield. From these observations we suggest that, in DCMU-poisoned chloroplasts, the fluorescence quenching with PMS occurrs by a mechanism unrelated to the generation of a phosphyorylation potential. With chloroplasts unpoisoned by DCMU, PMS quenches fluorescence and considerably stimulates proton uptake, the pH gradient and phosphorylation. However, in this case, PMS serves to restore net electron transport.", "contents": "Evidence against proton gradient formation being the cause of chlorophyll fluorescence quenching by N-methylphenazonium methosulfate. In strong illumination, 3-(3, 4-dichlorophenyl)-1,1-dimethylurea (DCMU)-poisoned chloroplasts exhibit a high yield of chlorophyll fluorescence while P-700 turnover, proton uptake, and phosphorylation are inhibited and a pH gradient is undectectable. When 10muM N-methylphenazonium methosulfate (PMS) is included, the fluorescence yield in light is substantially reduced, and when 100 muM ascorbate is also included, the yield is diminished approximately to the level in darkness. Only very slight increases in P-700 turnover and proton uptake (but no detectable pH gradient) accompany the fluorescence yield decline. When 10muM PMS and 15 mM ascorbate are added to poisoned chloroplasts (the oxygen concentration being greatly reduced), P-700 turnover, proton uptake, the pH gradient and phosphorylation all reach high levels. In this case, the yield of chlorophyll fluorescence is low and is the same in both light and dark. Further addition of an uncoupler eliminates proton uptake, the pH gradient and phosphorylation but does not significantly elevate the fluorescence yield. From these observations we suggest that, in DCMU-poisoned chloroplasts, the fluorescence quenching with PMS occurrs by a mechanism unrelated to the generation of a phosphyorylation potential. With chloroplasts unpoisoned by DCMU, PMS quenches fluorescence and considerably stimulates proton uptake, the pH gradient and phosphorylation. However, in this case, PMS serves to restore net electron transport."}
{"id": "PMID:4144", "title": "The accumulation of superoxide radical during the aerobic action of xanthine oxidase. A requiem for H2O4.", "content": "The action of xanthine oxidase upon acetaldehyde or xanthine at pH 10.2 has been shown to be accompanied by substantial accumulation of O2- during the first few minutes of the reaction. H2O2 decreases this accumulation of O2- presumably because of the Haber-Weiss reaction (H2O2+O2- leads to OH- +OH+O2) and very small amounts of superoxide dismutase eliminate it. This accumulation of O2- was demonstrated in terms of a burst of reduction of cytochrome c, seen when the latter compound was added after aerobic preincubation of xanthine oxidase with its substrate. The kinetic peculiarities of the luminescence seen in the presence of luminol, which previously led to the proposal of H2O4-, can now be satisfactorily explained entirely on the basis of known radical intermediates.", "contents": "The accumulation of superoxide radical during the aerobic action of xanthine oxidase. A requiem for H2O4. The action of xanthine oxidase upon acetaldehyde or xanthine at pH 10.2 has been shown to be accompanied by substantial accumulation of O2- during the first few minutes of the reaction. H2O2 decreases this accumulation of O2- presumably because of the Haber-Weiss reaction (H2O2+O2- leads to OH- +OH+O2) and very small amounts of superoxide dismutase eliminate it. This accumulation of O2- was demonstrated in terms of a burst of reduction of cytochrome c, seen when the latter compound was added after aerobic preincubation of xanthine oxidase with its substrate. The kinetic peculiarities of the luminescence seen in the presence of luminol, which previously led to the proposal of H2O4-, can now be satisfactorily explained entirely on the basis of known radical intermediates."}
{"id": "PMID:4145", "title": "The 520 nm absorbance changes in Scenedesmus obliquus and its relation to photosystem I.", "content": "The kinetics (region of seconds) of the light-induced 520 nm absorbance changes and its dark reversal have been studied in detail in the wild type and in some pigment and photosynthetic mutants of Scenedesmus obliquus. The following 5 lines of evidence led us to conclude that the signal is entirely due to the photosystem I reaction modified by electron flow from Photosystem II. Gradual blocking of the electron transport with 3(3,4-dichlorophenyl)-1,1-dimethylurea resulted in diminution and ultimate elimination of the biphasic nature of the signal without reducing the extent of the absorbance change or of the dark kinetics. On the contrary, blocking electron flow at the oxidizing side of plastoquinone with 2,5-dibromo-3-methyl-6-isoprophyl-p-benzoquinone or inactivating the plastocyanin with KCN, prolonged the dark reversal of the absorbance change apart from abolishing the biphasic nature of the signal. Action spectra clearly indicate that the main signal (I) is due to electron flow in Photosystem I and that its modification (Signal II) is due to the action of Photosystem II. Signal I is pH independent, whereas Signal II demonstrates a strong pH dependence, parallel to the O2-evolving capacity of the cells. Chloroplast particles isolated from the wild type Scenedesmus cells demonstrated in the absence of any added artificial electron donor or acceptor and also under non-phosphorylation conditions the 520 nm absorbance change with approximately the same magnitude as whole cells. The dark kinetics of the particles were comparatively slower. Removal of plastocyanin and other electron carriers by washing with Triton X-100 slowed down the kinetics of the dark reversal reaction to a greater extent. A similar positive absorbance change at 520 nm and slow dark reversal  was also observed in the Photosystem I particles prepared by the Triton method. Mutant C-6E, which contains neither carotenoids nor chlorophyll b and lacks Photosystem II activity, demonstrates a normal signal I of the 520 nm absorbance change. This latter result contradicts the postulate that carotenoids are the possible cause of the 520 nm absorbance change.", "contents": "The 520 nm absorbance changes in Scenedesmus obliquus and its relation to photosystem I. The kinetics (region of seconds) of the light-induced 520 nm absorbance changes and its dark reversal have been studied in detail in the wild type and in some pigment and photosynthetic mutants of Scenedesmus obliquus. The following 5 lines of evidence led us to conclude that the signal is entirely due to the photosystem I reaction modified by electron flow from Photosystem II. Gradual blocking of the electron transport with 3(3,4-dichlorophenyl)-1,1-dimethylurea resulted in diminution and ultimate elimination of the biphasic nature of the signal without reducing the extent of the absorbance change or of the dark kinetics. On the contrary, blocking electron flow at the oxidizing side of plastoquinone with 2,5-dibromo-3-methyl-6-isoprophyl-p-benzoquinone or inactivating the plastocyanin with KCN, prolonged the dark reversal of the absorbance change apart from abolishing the biphasic nature of the signal. Action spectra clearly indicate that the main signal (I) is due to electron flow in Photosystem I and that its modification (Signal II) is due to the action of Photosystem II. Signal I is pH independent, whereas Signal II demonstrates a strong pH dependence, parallel to the O2-evolving capacity of the cells. Chloroplast particles isolated from the wild type Scenedesmus cells demonstrated in the absence of any added artificial electron donor or acceptor and also under non-phosphorylation conditions the 520 nm absorbance change with approximately the same magnitude as whole cells. The dark kinetics of the particles were comparatively slower. Removal of plastocyanin and other electron carriers by washing with Triton X-100 slowed down the kinetics of the dark reversal reaction to a greater extent. A similar positive absorbance change at 520 nm and slow dark reversal  was also observed in the Photosystem I particles prepared by the Triton method. Mutant C-6E, which contains neither carotenoids nor chlorophyll b and lacks Photosystem II activity, demonstrates a normal signal I of the 520 nm absorbance change. This latter result contradicts the postulate that carotenoids are the possible cause of the 520 nm absorbance change."}
{"id": "PMID:4147", "title": "Pyruvate flux into resealed ghosts from human erythrocytes.", "content": "The kinetics of pyruvate transport across the isolated red blood cell membrane were studied by a simple and precise spectrophotometric method: following the oxidation of NADH via lactate dehydrogenase trapped within resealed ghosts. The initial rate of pyruvate entry was linear. Influx was limited by saturation at high pyruvate concentration. Pyruvate influx was greatly stimulated by increasing ionic strength in the outer but not the inner aqueous compartment. The Km ranged from 15.0 mM at mu = 0.05 to 3.7 mM at mu = 0.01, while the V went from 0.611 - 10(15) to 0.137 - 10(-15) mol - min-1 - ghost-1. Ionic strength was shown to affect the translocation step and not pyruvate binding. The energy of activation of pyruvate flux into resealed ghosts was 25 kcal/mol, similar to that found in intact red blood cells. Inhibitors of pyruvate influx included such anions as thiocyanate, chloride, bicarbonate, alpha-cyanocinnamate, salicylate and ketomalonate (but not acetate); noncompetitive inhibitors were phloretin, 1-fluoro-2,4-dinitrobenzene, 4-acetamido-4'-isothiocyanate-stilbene-2,2'-disulfonic acid and o-phenanthroline/CuSO4 mixtures. The last reagent, known to induce disulfide links in certain membrane proteins, blocked the ionic strength stimulation of pyruvate influx in this study.", "contents": "Pyruvate flux into resealed ghosts from human erythrocytes. The kinetics of pyruvate transport across the isolated red blood cell membrane were studied by a simple and precise spectrophotometric method: following the oxidation of NADH via lactate dehydrogenase trapped within resealed ghosts. The initial rate of pyruvate entry was linear. Influx was limited by saturation at high pyruvate concentration. Pyruvate influx was greatly stimulated by increasing ionic strength in the outer but not the inner aqueous compartment. The Km ranged from 15.0 mM at mu = 0.05 to 3.7 mM at mu = 0.01, while the V went from 0.611 - 10(15) to 0.137 - 10(-15) mol - min-1 - ghost-1. Ionic strength was shown to affect the translocation step and not pyruvate binding. The energy of activation of pyruvate flux into resealed ghosts was 25 kcal/mol, similar to that found in intact red blood cells. Inhibitors of pyruvate influx included such anions as thiocyanate, chloride, bicarbonate, alpha-cyanocinnamate, salicylate and ketomalonate (but not acetate); noncompetitive inhibitors were phloretin, 1-fluoro-2,4-dinitrobenzene, 4-acetamido-4'-isothiocyanate-stilbene-2,2'-disulfonic acid and o-phenanthroline/CuSO4 mixtures. The last reagent, known to induce disulfide links in certain membrane proteins, blocked the ionic strength stimulation of pyruvate influx in this study."}
{"id": "PMID:4148", "title": "Heme models. I. Solution behavior of a water soluble iron porphyrin.", "content": "A well-behaved water soluble iron-porphyrin system, meso-tetra-(4-carboxyphenyl) porphinato iron (III) was synthesized. Its solution behavior is described using visable and electron paramagnetic resonance (EPR) spectroscopy. The complex exists in solution as three distinct forms of bridged dimers, oxo, hydroxo and aquo, with the following pK's: oxo + H+ in equilibrium hydroxo, pK = 9.58; hydroxo + H+ in equilibrium aquo, pK = 6.72. In the presence of excess imidazole the second pK is found to be 7.05. Detailed analysis of the interaction of the hydroxo-bridged form with imidazole is presented. It is found that one dimer unit simultaneously binds two imidazole molecules, with an over-all equilibrium constant log Keq = -1.22. EPR spectra are presented for the various forms of iron-porphyrin discussed.", "contents": "Heme models. I. Solution behavior of a water soluble iron porphyrin. A well-behaved water soluble iron-porphyrin system, meso-tetra-(4-carboxyphenyl) porphinato iron (III) was synthesized. Its solution behavior is described using visable and electron paramagnetic resonance (EPR) spectroscopy. The complex exists in solution as three distinct forms of bridged dimers, oxo, hydroxo and aquo, with the following pK's: oxo + H+ in equilibrium hydroxo, pK = 9.58; hydroxo + H+ in equilibrium aquo, pK = 6.72. In the presence of excess imidazole the second pK is found to be 7.05. Detailed analysis of the interaction of the hydroxo-bridged form with imidazole is presented. It is found that one dimer unit simultaneously binds two imidazole molecules, with an over-all equilibrium constant log Keq = -1.22. EPR spectra are presented for the various forms of iron-porphyrin discussed."}
{"id": "PMID:4149", "title": "17 beta-Hydroxysteroid dehydrogenase of the sheep ovary : purification, properties and substrate binding site.", "content": "Sheep ovarian 17 beta HSDH has been purified about 1000 fold to a specific activity of 0.5 IU/mg protein, using DEAE cellulose chromatography, affinity chromatography on estrone-amino caproate-Sepharose and a second DEAE cellulose chromatography. The molecular weight is 70,000 ; the pH optimum for activity is 9.2 and the energy of activation is 16.5 Kcal/mole. The kinetics of the oxidation of estradiol and many analogues have been studied at various concentrations and in the presence of different amounts of coenzyme. The data are in agreement with a compulsory order mechanism with the binding of NAD+ as the first substrate. Sheep ovarian 17 beta HSDH accepts subtituents in position C3, C11, C13 ; the substrate binding site is open in this region. On the contrary, the binding requirements are strict for the region of C10 since the presence of a C19 methyl group impairs binding and (or) oxidation of the steroid. Sheep ovarian and human placental 17 beta HSDH have close analogies : molecular weight, pH optimum, substrate binding site requirements. Their reaction mechanisms are different : random for the placental 17 beta HSDH, compulsory order for the ovarian 17 beta HSDH : this can be explained by the effect of the coenzyme upon the binding of the substrate : without effect on placental enzyme, the coenzyme fixation enhances the affinity of the ovarian 17 beta HSDH for any substrate.", "contents": "17 beta-Hydroxysteroid dehydrogenase of the sheep ovary : purification, properties and substrate binding site. Sheep ovarian 17 beta HSDH has been purified about 1000 fold to a specific activity of 0.5 IU/mg protein, using DEAE cellulose chromatography, affinity chromatography on estrone-amino caproate-Sepharose and a second DEAE cellulose chromatography. The molecular weight is 70,000 ; the pH optimum for activity is 9.2 and the energy of activation is 16.5 Kcal/mole. The kinetics of the oxidation of estradiol and many analogues have been studied at various concentrations and in the presence of different amounts of coenzyme. The data are in agreement with a compulsory order mechanism with the binding of NAD+ as the first substrate. Sheep ovarian 17 beta HSDH accepts subtituents in position C3, C11, C13 ; the substrate binding site is open in this region. On the contrary, the binding requirements are strict for the region of C10 since the presence of a C19 methyl group impairs binding and (or) oxidation of the steroid. Sheep ovarian and human placental 17 beta HSDH have close analogies : molecular weight, pH optimum, substrate binding site requirements. Their reaction mechanisms are different : random for the placental 17 beta HSDH, compulsory order for the ovarian 17 beta HSDH : this can be explained by the effect of the coenzyme upon the binding of the substrate : without effect on placental enzyme, the coenzyme fixation enhances the affinity of the ovarian 17 beta HSDH for any substrate."}
{"id": "PMID:4150", "title": "Complete purification and studies on the structural and kinetic properties of two forms of yeast valyl-tRNA synthetase.", "content": "Two forms of baker's yease valyl-tRNA synthetase have been purified to apparent homogeneity by classical methods. It was demonstrated that one of the two forms of the enzyme originates from the other by proteolysis, the respective amounts of each form depending on the physiological state of the yeast. The species mainly isolated from exponential growing yeast cells is a monomer of 130,000 daltons molecular weight. In stationary phase cells or in commercial yeast the major species is a degraded monomer of 120,000 daltons molecular weight ; however when the purification is carried out in the presence of phenylmethyl-sulphonyl fluoride, or diisopropylfluorophosphate large amounts of the not - degreded monomer can be obtained. Of great practical usefulness is the fact that large amounts of the native enzyme can be obtained pure after only two chromatographic steps on DEAE-cellulose and hydroxylapatite. The kinetic constants for valine, ATP and tRNAVal were determined, as well as the optimum aminoacylation conditions. It was found that the specific activity of the nondegraded valyl-tRNA synthetase is higher than that of the proteolysed enzyme for the aminoacylation reaction. On the contrary, both forms have the same ATP-pyroposphate exchange activity. The amino acids composition of the native enzyme was established. The tryptic fingerprints of the two valyl-tRNA synthetases were studied. Essentially similar maps were obtained. The number of the spots in the fingerprints indicates that the enzymes contain a high proportion of repeated sequences.", "contents": "Complete purification and studies on the structural and kinetic properties of two forms of yeast valyl-tRNA synthetase. Two forms of baker's yease valyl-tRNA synthetase have been purified to apparent homogeneity by classical methods. It was demonstrated that one of the two forms of the enzyme originates from the other by proteolysis, the respective amounts of each form depending on the physiological state of the yeast. The species mainly isolated from exponential growing yeast cells is a monomer of 130,000 daltons molecular weight. In stationary phase cells or in commercial yeast the major species is a degraded monomer of 120,000 daltons molecular weight ; however when the purification is carried out in the presence of phenylmethyl-sulphonyl fluoride, or diisopropylfluorophosphate large amounts of the not - degreded monomer can be obtained. Of great practical usefulness is the fact that large amounts of the native enzyme can be obtained pure after only two chromatographic steps on DEAE-cellulose and hydroxylapatite. The kinetic constants for valine, ATP and tRNAVal were determined, as well as the optimum aminoacylation conditions. It was found that the specific activity of the nondegraded valyl-tRNA synthetase is higher than that of the proteolysed enzyme for the aminoacylation reaction. On the contrary, both forms have the same ATP-pyroposphate exchange activity. The amino acids composition of the native enzyme was established. The tryptic fingerprints of the two valyl-tRNA synthetases were studied. Essentially similar maps were obtained. The number of the spots in the fingerprints indicates that the enzymes contain a high proportion of repeated sequences."}
{"id": "PMID:4151", "title": "[Rat liver plasma membrane phospholipase A].", "content": "The plasma membranes phospholipase A2 studied in situ shows very little sensitivity for pH variations ; the optimal concentration for Ca++ is 5 mM ; the enzymatic kinetics are of the Michaelis type. An inactive state of the phospholipase A2 exists : when rats are injected with heparin, their plasma membranes contain a very low phospholipase A2 activity. These membranes recover a high A2 activity if they are incubated in the presence of a rat platelets lysate. Treatment of membranes by NaCl 1 M displaces phospholipase A1 and phospholipase A2 but for the latter only when being in active state. Treatment of animals, conditions of preparation and of incubation of membranes influence the respective amounts of phospholipases A1 and A2 present in these membranes and are discussed in this paper. The localisation of these enzymatic proteins inside the membrane according to the membranous model proposed by Singer et al. [18] is also discussed.", "contents": "[Rat liver plasma membrane phospholipase A]. The plasma membranes phospholipase A2 studied in situ shows very little sensitivity for pH variations ; the optimal concentration for Ca++ is 5 mM ; the enzymatic kinetics are of the Michaelis type. An inactive state of the phospholipase A2 exists : when rats are injected with heparin, their plasma membranes contain a very low phospholipase A2 activity. These membranes recover a high A2 activity if they are incubated in the presence of a rat platelets lysate. Treatment of membranes by NaCl 1 M displaces phospholipase A1 and phospholipase A2 but for the latter only when being in active state. Treatment of animals, conditions of preparation and of incubation of membranes influence the respective amounts of phospholipases A1 and A2 present in these membranes and are discussed in this paper. The localisation of these enzymatic proteins inside the membrane according to the membranous model proposed by Singer et al. [18] is also discussed."}
{"id": "PMID:4152", "title": "Phosphate uptake in Chlorella pyrenoidosa : II. Effect of pH and of SH reagents.", "content": "The sensitivity of the phosphate transport system to pCMPS after phosphate starvation is dependent on protein synthesis. This fact is related to the development of transport activity at alkaline pH. In non-starved cells, the presence of only one peak of maximal activity for phosphate uptake at neutral pH (at low and high concentration) has been observed. However, in phosphate starved cells, two peaks of maximal activity (at low phosphate concentration) at neutral and alkaline pH are present. In starved cells, pCMPS inhibits more intensely the phosphate transport activity at alkaline pH than at neutral pH. By contrast, NEM inhibits the phosphate transport more strongly at neutral than at alkaline pH. Phosphate uptake at neutral and alkaline pH are sensitive to osmotic shock, but phosphate uptake at alkaline pH is decreased more than at neutral pH. The results could be interpreted either by assuming that the membrane surroundings change during phosphate starvation or that two transport systems are present in starved cells whereas only one transport system exists in non-starved cells.", "contents": "Phosphate uptake in Chlorella pyrenoidosa : II. Effect of pH and of SH reagents. The sensitivity of the phosphate transport system to pCMPS after phosphate starvation is dependent on protein synthesis. This fact is related to the development of transport activity at alkaline pH. In non-starved cells, the presence of only one peak of maximal activity for phosphate uptake at neutral pH (at low and high concentration) has been observed. However, in phosphate starved cells, two peaks of maximal activity (at low phosphate concentration) at neutral and alkaline pH are present. In starved cells, pCMPS inhibits more intensely the phosphate transport activity at alkaline pH than at neutral pH. By contrast, NEM inhibits the phosphate transport more strongly at neutral than at alkaline pH. Phosphate uptake at neutral and alkaline pH are sensitive to osmotic shock, but phosphate uptake at alkaline pH is decreased more than at neutral pH. The results could be interpreted either by assuming that the membrane surroundings change during phosphate starvation or that two transport systems are present in starved cells whereas only one transport system exists in non-starved cells."}
{"id": "PMID:4156", "title": "Possible occurrence for histidyl and cysteyl residues in the catalytic center of rat liver mitochondrial D (-)-beta-hydroxybutyrate dehydrogenase.", "content": "1. Rat liver mitochondrial D(-)-beta-hydroxybutyrate dehydrogenase (submitochondrial particles and partially purified preparation) is inhibited by some dicarboxylates, especially by malonate and succinate. The inhibition is reversible and competitive with beta-hydroxybutyrate while uncompetitive with acetoacetate, NAD and NADH: the inhibition is maximal at pH 6 and decrease with increasing pH. 2. Diethylpyrocarbonate (which reacts preferentially with histidyl residues at pH 6.6) inactivates the dehydrogenase at pH 6.1, beta-hydroxybutyrate protects against inactivation, this inactivation being almost completely released by hydroxylamine. The diethylpyrocarbonate-treated enzyme shows an absorbance increase at 242 nm which is characterisitic of reaction between diethylpyrocarbonate and histidyl residue. 3. The optimum pH of the enzyme for beta-hydroxybutyrate oxidation is around 8.2, while for acetoacetate reduction, the optimum pH is around 7. 4. All these results favour the existence of a histidyl residue in the catalytic center and taking into account previous results concerning the effect of thiol reagents on the same enzyme and especially, the protective effect of NAD+ and NADH against these reagents [11] we discuss the possible occurrence of, at least, one histidyl and one cysteyl residue on the catalytic center.", "contents": "Possible occurrence for histidyl and cysteyl residues in the catalytic center of rat liver mitochondrial D (-)-beta-hydroxybutyrate dehydrogenase. 1. Rat liver mitochondrial D(-)-beta-hydroxybutyrate dehydrogenase (submitochondrial particles and partially purified preparation) is inhibited by some dicarboxylates, especially by malonate and succinate. The inhibition is reversible and competitive with beta-hydroxybutyrate while uncompetitive with acetoacetate, NAD and NADH: the inhibition is maximal at pH 6 and decrease with increasing pH. 2. Diethylpyrocarbonate (which reacts preferentially with histidyl residues at pH 6.6) inactivates the dehydrogenase at pH 6.1, beta-hydroxybutyrate protects against inactivation, this inactivation being almost completely released by hydroxylamine. The diethylpyrocarbonate-treated enzyme shows an absorbance increase at 242 nm which is characterisitic of reaction between diethylpyrocarbonate and histidyl residue. 3. The optimum pH of the enzyme for beta-hydroxybutyrate oxidation is around 8.2, while for acetoacetate reduction, the optimum pH is around 7. 4. All these results favour the existence of a histidyl residue in the catalytic center and taking into account previous results concerning the effect of thiol reagents on the same enzyme and especially, the protective effect of NAD+ and NADH against these reagents [11] we discuss the possible occurrence of, at least, one histidyl and one cysteyl residue on the catalytic center."}
{"id": "PMID:4153", "title": "[Mechanism of glutaraldehyde-protein bond formation].", "content": "Commercial aqueous 25% glutaraldehyde solutions contain no stable derivative of this aldehyde, but compounds of variable molecular weight which easily revert to glutaraldehyde. The effect of pH on the reaction of glutarldehyde with amino acids and on the stability of the products under acid conditions, shows the importance of the structure modification of the dialdehyde which occurs when pH increases, and even leads to precipitation in highly alkaline solutions. This precipitate results from aldol condensation of glutaraldehyde molecules. It contains aldehyd groups conjugated with ethylenic double bonds. Such a structure reacts with amino groups to give an imino bond, stabilized by resonance with the ethylenic bond, and does not undergo Michael-type addition reactions. Therefore, glutaraldehyde does not react with proteins under its free form, but as an unsaturated polymer, which gives imino bonds stabilized by conjugation.", "contents": "[Mechanism of glutaraldehyde-protein bond formation]. Commercial aqueous 25% glutaraldehyde solutions contain no stable derivative of this aldehyde, but compounds of variable molecular weight which easily revert to glutaraldehyde. The effect of pH on the reaction of glutarldehyde with amino acids and on the stability of the products under acid conditions, shows the importance of the structure modification of the dialdehyde which occurs when pH increases, and even leads to precipitation in highly alkaline solutions. This precipitate results from aldol condensation of glutaraldehyde molecules. It contains aldehyd groups conjugated with ethylenic double bonds. Such a structure reacts with amino groups to give an imino bond, stabilized by resonance with the ethylenic bond, and does not undergo Michael-type addition reactions. Therefore, glutaraldehyde does not react with proteins under its free form, but as an unsaturated polymer, which gives imino bonds stabilized by conjugation."}
{"id": "PMID:4157", "title": "Purification and properties of cyclic AMP dependent and independent protein kinases from rat pancreas.", "content": "Three protein kinases Ko, K1, and KII have been extracted from rat pancreas homogenate, Ko is not stimulated by cyclic AMP. K1 is poorly stimulated by cyclic AMP (1.3 times), Ku is highly stimulated (6 times). The specificity of KII with respect to various nucleotides and cyclic nucleotides has been determined. K1 and KII account for the total cyclic AMP dependent protein kinase activity in the homogenate.", "contents": "Purification and properties of cyclic AMP dependent and independent protein kinases from rat pancreas. Three protein kinases Ko, K1, and KII have been extracted from rat pancreas homogenate, Ko is not stimulated by cyclic AMP. K1 is poorly stimulated by cyclic AMP (1.3 times), Ku is highly stimulated (6 times). The specificity of KII with respect to various nucleotides and cyclic nucleotides has been determined. K1 and KII account for the total cyclic AMP dependent protein kinase activity in the homogenate."}
{"id": "PMID:4158", "title": "[Decanoic acid, new precursor for in vitro biosynthesis of oleic acid by a plant subcellular fraction].", "content": "Various membraneous fractions prepared from a cauliflower homogenate synthesize radioactive oleic acid when they are incubated in a 14C-decanolate solution. The more active fraction is formed of vesicles sedimenting at 30,000 g x 20 mn (heavy microsomes). The labelled precursor is transformed by this fraction mainly into oleic acid and hydroxyacids. ATP, NADPH, CoA and oxygen are required for these reactions. Labelled fatty acids, longer than lauric and (i.e. 14C-myristic, 14C-palmitic and 14C-stearic acids) are not transformed into oleic acid by the subcellular fraction studied in this paper.", "contents": "[Decanoic acid, new precursor for in vitro biosynthesis of oleic acid by a plant subcellular fraction]. Various membraneous fractions prepared from a cauliflower homogenate synthesize radioactive oleic acid when they are incubated in a 14C-decanolate solution. The more active fraction is formed of vesicles sedimenting at 30,000 g x 20 mn (heavy microsomes). The labelled precursor is transformed by this fraction mainly into oleic acid and hydroxyacids. ATP, NADPH, CoA and oxygen are required for these reactions. Labelled fatty acids, longer than lauric and (i.e. 14C-myristic, 14C-palmitic and 14C-stearic acids) are not transformed into oleic acid by the subcellular fraction studied in this paper."}
{"id": "PMID:4154", "title": "[Acetylcholinesterase. II. Experimental aspects of interaction with reversible effectors under conditions of high ionic strength].", "content": "Interaction of usual effectors with acetylcholinesterase (EC 3.1.1.7) from bovine erythrocytes was examined under conditions of high ionic strength (gamma/2 greater than or equal to 0,1). Detailed kinetic investigation of the hydrolysis of acetylcholine by acetylcholinesterase in the presence of modifiers shows that the effects produced by numerous quaternary nitrogen compounds on the enzyme can be explained on the basis of binding of the effectors to the anionic subsite of the active center. The various kinetic behaviors, that are observed, are dependent on the relative values of the deacetylation rate constant ak of the complex acetylated enzyme-modifier and of the rate constant k-2 defined by : (see article) with respect to the value of the deacetylation rate constant K of the acetylated enzyme. If a identical to [1--(k/k-2)]-1, it is shown that interaction of the enzyme with tetraethylammonium, pentamethonium, hexamethonium and gallamine ions is characterized by : a greater than a and k-2 greater than k therefore, these modifiers accelerate deacetylation. On the other hand, inhibition of acetylcholinestase by methylpyridinium, d-tubocurarine, tetra-n-propylammonium, tetra-n-butylammonium, decamethonium and succinylbischoline is consistent with one of the conditions : a less than a and k-2 greater than or equal to k or a greater than a and k-2 less than k and inhibition by tetramethylammonium, phenyltrimethylammonium, 3-hydroxyphenyl-triethylammonium, N-methylacridinium and bis (3-aminopyridinium)-1,10-decane ions agrees with one of the two previous conditions or with : (see article) consequently, the effect of these ligands on the deacetylation step is undetermined. However, the effects of choline chloride, thiazinamium methyl sulfate and thioridazine hydrochloride are not entirely consistent with this mechanism but support the existence of a functional peripheral anionic site which is distinct from the anionic subsite of the active center.", "contents": "[Acetylcholinesterase. II. Experimental aspects of interaction with reversible effectors under conditions of high ionic strength]. Interaction of usual effectors with acetylcholinesterase (EC 3.1.1.7) from bovine erythrocytes was examined under conditions of high ionic strength (gamma/2 greater than or equal to 0,1). Detailed kinetic investigation of the hydrolysis of acetylcholine by acetylcholinesterase in the presence of modifiers shows that the effects produced by numerous quaternary nitrogen compounds on the enzyme can be explained on the basis of binding of the effectors to the anionic subsite of the active center. The various kinetic behaviors, that are observed, are dependent on the relative values of the deacetylation rate constant ak of the complex acetylated enzyme-modifier and of the rate constant k-2 defined by : (see article) with respect to the value of the deacetylation rate constant K of the acetylated enzyme. If a identical to [1--(k/k-2)]-1, it is shown that interaction of the enzyme with tetraethylammonium, pentamethonium, hexamethonium and gallamine ions is characterized by : a greater than a and k-2 greater than k therefore, these modifiers accelerate deacetylation. On the other hand, inhibition of acetylcholinestase by methylpyridinium, d-tubocurarine, tetra-n-propylammonium, tetra-n-butylammonium, decamethonium and succinylbischoline is consistent with one of the conditions : a less than a and k-2 greater than or equal to k or a greater than a and k-2 less than k and inhibition by tetramethylammonium, phenyltrimethylammonium, 3-hydroxyphenyl-triethylammonium, N-methylacridinium and bis (3-aminopyridinium)-1,10-decane ions agrees with one of the two previous conditions or with : (see article) consequently, the effect of these ligands on the deacetylation step is undetermined. However, the effects of choline chloride, thiazinamium methyl sulfate and thioridazine hydrochloride are not entirely consistent with this mechanism but support the existence of a functional peripheral anionic site which is distinct from the anionic subsite of the active center."}
{"id": "PMID:4159", "title": "[Interactions of phosphorylethanolamine analogs with phosphorylethanolamine-citidylyltransferase].", "content": "Kinetic studies of ethanolaminephosphate-cytidylyltransferase (E.C. 2.7.7.14) from rat liver have been carried out in presence of structural analogues of ethanolaminephosphate : these compounds acted as inhibitors of the enzyme: - 2-aminoethylphosphonate behaved as a substrate and a competitive inhibitor to phosphorylethanolamine: the Km value of 2-aminoethylphosphonate was nearly the same as its Ki value, at pH = 5,5 (30 X 10(-3) M and 24 x 10(-3) M, respectively). - 3-aminopropylphosphonate was also a competitive inhibitor. It appeared to be the best inhibitor at pH optimum (pH = 7,7). - 1-aminoethylphosphonate behaved as a noncompetitive inhibitor. However, cytidylyltransferase was relatively specific, inhibitions being always weak. Inhibitory power of phosphonates was stimulated by Mg++.", "contents": "[Interactions of phosphorylethanolamine analogs with phosphorylethanolamine-citidylyltransferase]. Kinetic studies of ethanolaminephosphate-cytidylyltransferase (E.C. 2.7.7.14) from rat liver have been carried out in presence of structural analogues of ethanolaminephosphate : these compounds acted as inhibitors of the enzyme: - 2-aminoethylphosphonate behaved as a substrate and a competitive inhibitor to phosphorylethanolamine: the Km value of 2-aminoethylphosphonate was nearly the same as its Ki value, at pH = 5,5 (30 X 10(-3) M and 24 x 10(-3) M, respectively). - 3-aminopropylphosphonate was also a competitive inhibitor. It appeared to be the best inhibitor at pH optimum (pH = 7,7). - 1-aminoethylphosphonate behaved as a noncompetitive inhibitor. However, cytidylyltransferase was relatively specific, inhibitions being always weak. Inhibitory power of phosphonates was stimulated by Mg++."}
{"id": "PMID:4160", "title": "[Purification and properties of aromatic L-amino acid decarboxylase (4.1.1.28) of rat brain].", "content": "L-aromatic aminoacid decarboxylase has been purified more than thousand times from homogenates of rat brain, in several steps : centrifugation, DEAE-cellulose, CM cellulose, hydroxylapatite, DEAE sephadex. Its properties have been studied, most of them on an intermediate fraction of the purification, because of the instability of the purified enzyme in spite of the addition of different stabilizing agents : the enzyme decarboxylates 5-hydroxytryptophan (5 HTP) and DOPA in a ratio constant throughout the purification but does not decarboxylate tryptophan, tyrosine, histidine at a measurable rate. Optimum pH, Km, Vm, have been measured with 5 HTP and DOPA as substrates. The enzyme has a molecular weight of 115.000, an apparent isoelectric point of 6,4-6,5. It is inhibited by serotonin, dopamine, some cations : Cu++, Fe++, Ni++ by N-ethylmaleimide, sodium dodecylsulfate. Some pyridoxal-5 phosphate (PLP) remains strongly bound to the enzyme. For relatively weak concentrations of substrate, the enzyme is inhibited by an excess of PLP ; for weak concentrations of PLP, the enzyme in inhibited by an excess of substrate, particularly of DOPA. We also observe a spontaneous decarboxylation of the substrates that reaches a plateau and is enhanced by high concentrations of PLP, by serotonin, dopamine, Cu++ and reduced by mercaptoethanol and the presence of crude or boiled homogenates. Several possible explanations of the spontaneous decarboxylation and of the enzymic inhibitions by an excess of PLP and by the substrates are given.", "contents": "[Purification and properties of aromatic L-amino acid decarboxylase (4.1.1.28) of rat brain]. L-aromatic aminoacid decarboxylase has been purified more than thousand times from homogenates of rat brain, in several steps : centrifugation, DEAE-cellulose, CM cellulose, hydroxylapatite, DEAE sephadex. Its properties have been studied, most of them on an intermediate fraction of the purification, because of the instability of the purified enzyme in spite of the addition of different stabilizing agents : the enzyme decarboxylates 5-hydroxytryptophan (5 HTP) and DOPA in a ratio constant throughout the purification but does not decarboxylate tryptophan, tyrosine, histidine at a measurable rate. Optimum pH, Km, Vm, have been measured with 5 HTP and DOPA as substrates. The enzyme has a molecular weight of 115.000, an apparent isoelectric point of 6,4-6,5. It is inhibited by serotonin, dopamine, some cations : Cu++, Fe++, Ni++ by N-ethylmaleimide, sodium dodecylsulfate. Some pyridoxal-5 phosphate (PLP) remains strongly bound to the enzyme. For relatively weak concentrations of substrate, the enzyme is inhibited by an excess of PLP ; for weak concentrations of PLP, the enzyme in inhibited by an excess of substrate, particularly of DOPA. We also observe a spontaneous decarboxylation of the substrates that reaches a plateau and is enhanced by high concentrations of PLP, by serotonin, dopamine, Cu++ and reduced by mercaptoethanol and the presence of crude or boiled homogenates. Several possible explanations of the spontaneous decarboxylation and of the enzymic inhibitions by an excess of PLP and by the substrates are given."}
{"id": "PMID:4161", "title": "[Characterization of some hydrolase activities in digestive juice of Achatina balteata].", "content": "The digestive juice of Achatina balteata, a giant snail of the West African Coast catalyses the hydrolysis of several natural and synthetic compounds. Enzymatic activities on lactose, o- and p-nitrophenyl-beta-D-galactoside, p-nitrophenyl-beta-D-glucoside, p-nitrophenyl-beta-D (and alpha-L-) fucoside, o-nitrophenyl-beta-D-xyloside, p-nitrophenyl-N-acetyl-beta-D-glucosaminide and phenolphthalein-glucuronide have been shown to be present. The effect of pH and substrate concentration on these activities were studied. The galactosidase, glucosidase and fucosidase activities were studied with respect to temperature, heat inactivation, pH stability and incubation with trypsin. Kinetic experiments suggest the presence of several galactosidase activities. This hypothesis is confirmed by specific staining after polyacrylamide gel electrophoresis. These activities showed a broad specificity towards galactosides and glucosides. The digestive juice showed no action on acetyl-L-tyrosine and benzoyl-L-arginine ethyl esters. However a small protease activity was observed on hemoglobine. No lipase activity was found. Sulfatase content was low compared to that of Helix pomatia.", "contents": "[Characterization of some hydrolase activities in digestive juice of Achatina balteata]. The digestive juice of Achatina balteata, a giant snail of the West African Coast catalyses the hydrolysis of several natural and synthetic compounds. Enzymatic activities on lactose, o- and p-nitrophenyl-beta-D-galactoside, p-nitrophenyl-beta-D-glucoside, p-nitrophenyl-beta-D (and alpha-L-) fucoside, o-nitrophenyl-beta-D-xyloside, p-nitrophenyl-N-acetyl-beta-D-glucosaminide and phenolphthalein-glucuronide have been shown to be present. The effect of pH and substrate concentration on these activities were studied. The galactosidase, glucosidase and fucosidase activities were studied with respect to temperature, heat inactivation, pH stability and incubation with trypsin. Kinetic experiments suggest the presence of several galactosidase activities. This hypothesis is confirmed by specific staining after polyacrylamide gel electrophoresis. These activities showed a broad specificity towards galactosides and glucosides. The digestive juice showed no action on acetyl-L-tyrosine and benzoyl-L-arginine ethyl esters. However a small protease activity was observed on hemoglobine. No lipase activity was found. Sulfatase content was low compared to that of Helix pomatia."}
{"id": "PMID:4162", "title": "Characterization of the mannosyl and fucosyl transferases in the ovine anterior pituitary glands.", "content": "Ovine anterior pituitary glands contain mannosyl- and fucosyl-transferases localized in the microsomes and able to incorporate mannose or fucose as such from GDP-mannose or GDP-fucose into endogenous glycoproteins. The requirements and conditions necessary for maximum activity were investigated. The value of the Km is very similar for the two enzyme systems, 3 X 10(-7) M in the case of mannosyl-transferases and 5 X 10(-7) M in the case of fucosyl-transferases.", "contents": "Characterization of the mannosyl and fucosyl transferases in the ovine anterior pituitary glands. Ovine anterior pituitary glands contain mannosyl- and fucosyl-transferases localized in the microsomes and able to incorporate mannose or fucose as such from GDP-mannose or GDP-fucose into endogenous glycoproteins. The requirements and conditions necessary for maximum activity were investigated. The value of the Km is very similar for the two enzyme systems, 3 X 10(-7) M in the case of mannosyl-transferases and 5 X 10(-7) M in the case of fucosyl-transferases."}
{"id": "PMID:4166", "title": "Adjuvant and immunostimulating activities of water-soluble substances extracted from Mycobacterium tuberculosis (var. hominis).", "content": "Water-soluble substances have been extracted from two strains of Mycobacterium tuberculosis var. hominis: the native hydrosoluble part (polysaccharide and peptidoglycan), a substance in which the polysaccharide moiety is less abundant than in the latter, the acetylated peptidoglycan and, finally a tetrasaccharide-heptapeptide. All four types of substances, when they were injected together with Freund's incomplete adjuvant, exerted an adjuvant effect on the production of delayed-type hypersensitivity to ovalbumin in the guinea pig and on the production of anti-influenza virus antibodies in the rabbit. Injected intravenously in the mouse, they increased the number of antibody-producing cells in the spleen and enhanced the graft versus host reaction; no effect was seen on the phagocytic activity of the reticulo-endothelial system. By contrast with wax D, the water-soluble substances were devoid of arthritis-inducing activity in the rat. Altogether, these water-soluble substances seem to be endowed with at least some of the adjuvant activities of Freund's complete adjuvant and some of the immunostimulant activities of a live Mycobacterium like BCG.", "contents": "Adjuvant and immunostimulating activities of water-soluble substances extracted from Mycobacterium tuberculosis (var. hominis). Water-soluble substances have been extracted from two strains of Mycobacterium tuberculosis var. hominis: the native hydrosoluble part (polysaccharide and peptidoglycan), a substance in which the polysaccharide moiety is less abundant than in the latter, the acetylated peptidoglycan and, finally a tetrasaccharide-heptapeptide. All four types of substances, when they were injected together with Freund's incomplete adjuvant, exerted an adjuvant effect on the production of delayed-type hypersensitivity to ovalbumin in the guinea pig and on the production of anti-influenza virus antibodies in the rabbit. Injected intravenously in the mouse, they increased the number of antibody-producing cells in the spleen and enhanced the graft versus host reaction; no effect was seen on the phagocytic activity of the reticulo-endothelial system. By contrast with wax D, the water-soluble substances were devoid of arthritis-inducing activity in the rat. Altogether, these water-soluble substances seem to be endowed with at least some of the adjuvant activities of Freund's complete adjuvant and some of the immunostimulant activities of a live Mycobacterium like BCG."}
{"id": "PMID:4167", "title": "Arylsulfatases isoenzymes in metachromatic leucodystrophy/detection of a new variant by electrophoresis improvement of quantitative assay.", "content": "Arylsulfatase A and B activities were assayed in leucocytes of 43 controls, 11 cases of Metachromatic Leucodystrophy and 7 parents or siblings of patients, using a new technique implying specific inhibitors for leucocyte enzymes. Heterozygotes can be determined, with a 50% value compared to the control, in variant B. Electrophoresis of leucocytes after enzymatic staining for arylsulfatase, is a complementary technique which allowed the detection of a new form of metachromatic leucodystrophy.", "contents": "Arylsulfatases isoenzymes in metachromatic leucodystrophy/detection of a new variant by electrophoresis improvement of quantitative assay. Arylsulfatase A and B activities were assayed in leucocytes of 43 controls, 11 cases of Metachromatic Leucodystrophy and 7 parents or siblings of patients, using a new technique implying specific inhibitors for leucocyte enzymes. Heterozygotes can be determined, with a 50% value compared to the control, in variant B. Electrophoresis of leucocytes after enzymatic staining for arylsulfatase, is a complementary technique which allowed the detection of a new form of metachromatic leucodystrophy."}
{"id": "PMID:4168", "title": "Intrahepatic lymphoid tissue graft: course of the Gvh reaction induced by Peyer's patches.", "content": "To investigate the thymus-dependent immune competence of Peyer's patches, the course of splenomegaly and hepatic perivascular infiltration (PVI) was studied as criteria of graft-versus-host reaction (GvhR). Parental or F1 hybrid lymphoid tissues, were intrahepatically implanted and the ability of Peyer's patches to induce a GvhR was compared to that of spleen, lymph nodes and thymus. A slight but significant delayed increase of spleen index was observed at the 40th post operative day following Peyer's patches implantation whereas the thymus did not induce any modification of this parameter. On the other hand, the PVI was a very early and precise criterion in monitoring the Gvh reaction induced by Peyer's patches, and allowed to postulate that at least one T-cell function is present within the Peyer's patches.", "contents": "Intrahepatic lymphoid tissue graft: course of the Gvh reaction induced by Peyer's patches. To investigate the thymus-dependent immune competence of Peyer's patches, the course of splenomegaly and hepatic perivascular infiltration (PVI) was studied as criteria of graft-versus-host reaction (GvhR). Parental or F1 hybrid lymphoid tissues, were intrahepatically implanted and the ability of Peyer's patches to induce a GvhR was compared to that of spleen, lymph nodes and thymus. A slight but significant delayed increase of spleen index was observed at the 40th post operative day following Peyer's patches implantation whereas the thymus did not induce any modification of this parameter. On the other hand, the PVI was a very early and precise criterion in monitoring the Gvh reaction induced by Peyer's patches, and allowed to postulate that at least one T-cell function is present within the Peyer's patches."}
{"id": "PMID:4172", "title": "Marine sterols. III--The sterol compositions of oceanic jellyfish. The use of gas chromatographic mass spectrometric techniques to identify unresolved components.", "content": "The sterol compositions of three oceanic jellyfish have been determined using gas chromatographic mass spectrometric techniques involving the use of two separate gas chromatographic column systems. The components in overlapping peaks have been identified by comparison of the mass spectra of peaks in the two column systems using subtractive techniques. A mid-water animal, Periphylla periphylla, was found to contain a very complex and unusual sterol profile including rare 5alpha-stanols, whereas two other oceanic jellyfish Pelagia noctiluca and Atolla wyvillei contained similar mixtures of delta5 sterols to those previously isolated from coastal species.", "contents": "Marine sterols. III--The sterol compositions of oceanic jellyfish. The use of gas chromatographic mass spectrometric techniques to identify unresolved components. The sterol compositions of three oceanic jellyfish have been determined using gas chromatographic mass spectrometric techniques involving the use of two separate gas chromatographic column systems. The components in overlapping peaks have been identified by comparison of the mass spectra of peaks in the two column systems using subtractive techniques. A mid-water animal, Periphylla periphylla, was found to contain a very complex and unusual sterol profile including rare 5alpha-stanols, whereas two other oceanic jellyfish Pelagia noctiluca and Atolla wyvillei contained similar mixtures of delta5 sterols to those previously isolated from coastal species."}
{"id": "PMID:4173", "title": "The gas chromatographic mass spectrometric determination of trifluoroacetic acid in biological fluid. Application to halothane metabolism.", "content": "The methyl ester of trifluoroacetic acid was prepared by reaction with N,N'-dimethylformamide dimethylacetal and was successfully passed through a gas chromatograph. Trifluoroacetic acid was detected by the use of gas chromatography and low and high resolution gas chromatography mass spectrometry in an acidic extract of an incubation medium containing microsomes, reduced nicotinamide adenine dinucleotide phosphate, oxygen and halothane. However, trifluoroacetic acid could not be detected when nicotinamide adenine dinucleotide or oxygen was omitted from the incubation system. From these results, it was proved that halothane is oxidatively metabolized to trifluoroacetic acid by hepatic microsomes.", "contents": "The gas chromatographic mass spectrometric determination of trifluoroacetic acid in biological fluid. Application to halothane metabolism. The methyl ester of trifluoroacetic acid was prepared by reaction with N,N'-dimethylformamide dimethylacetal and was successfully passed through a gas chromatograph. Trifluoroacetic acid was detected by the use of gas chromatography and low and high resolution gas chromatography mass spectrometry in an acidic extract of an incubation medium containing microsomes, reduced nicotinamide adenine dinucleotide phosphate, oxygen and halothane. However, trifluoroacetic acid could not be detected when nicotinamide adenine dinucleotide or oxygen was omitted from the incubation system. From these results, it was proved that halothane is oxidatively metabolized to trifluoroacetic acid by hepatic microsomes."}
{"id": "PMID:4174", "title": "[Reciprocal influence of the graft vs. host reaction and pregnancy].", "content": "The graft versus host reaction (GVHR) was induced in mouse females-hybrids F1 (CBA X C57BL/6) by intravenous injection of suspension of the lymphoid cells of the spleen and of lymphoid nodes from C57BL/6 mouse females. Pregnancy resulted from interbreeding of the test females with syngenic males 1--5 days before, and 1--10, 10--20, 30--40 and more than 40 days after the moment of the lymphoid cells injection, aggravated the GVHR induced transplantation disease. At the same time the GVHR under these conditions decreased the percentage of pregnant animals and brought to child-bearing disfunction of the test animals (stillbirth, death of pregnant females, miscarriage). In some of the test mice aggravation of the GVHR was observed after delivery. Survival of the progeny decreased.", "contents": "[Reciprocal influence of the graft vs. host reaction and pregnancy]. The graft versus host reaction (GVHR) was induced in mouse females-hybrids F1 (CBA X C57BL/6) by intravenous injection of suspension of the lymphoid cells of the spleen and of lymphoid nodes from C57BL/6 mouse females. Pregnancy resulted from interbreeding of the test females with syngenic males 1--5 days before, and 1--10, 10--20, 30--40 and more than 40 days after the moment of the lymphoid cells injection, aggravated the GVHR induced transplantation disease. At the same time the GVHR under these conditions decreased the percentage of pregnant animals and brought to child-bearing disfunction of the test animals (stillbirth, death of pregnant females, miscarriage). In some of the test mice aggravation of the GVHR was observed after delivery. Survival of the progeny decreased."}
{"id": "PMID:4175", "title": "Studies on gamma-glutamyl transpeptidase in human and rabbit erythrocytes.", "content": "Gamma-glutamyl transpeptidase transfers the gamma-glutamyl moiety of glutathione to a variety of acceptor amino acids. Through the operation of the gamma-glutamyl-cyclotransferase cycle, this enzyme has been implicated in the transport of amino acids into cells, especially the cells of the proximal tubules of kidney. It has been reported to be present in rabbit erythrocytes. However, using white cell-free preparations, we have not been able to demonstrate the presence of gamma-glutamyl transpeptidase in human or rabbit erythrocytes either by measuring the utilization of GSH or by following the formation of the product. 14C-L-methionine was used as acceptor amino acid, and the formation of gamma-glutamyl-14C-L-methionine was followed. Using similar conditions, we have been able to demonstrate the presence of gamma-glutamyl transpeptidase in human and rabbit leukocytes and in human kidney. In contrast to a previous report, we were unable to find the accumulation of 5-oxoproline, an intermediate of the gamma-glutamyl-cyclotransferase pathway in human red cells incubated in Krebs-Ringer solution. Immunologic studies demonstrated that human red cell membranes contained no protein antigenically similar to kidney gamma-glutamyl transpeptidase. Thus our studies indicated that in human and rabbit erythrocytes, the gamma-glutamyl transpeptidase-cyclotransferase pathway was not operative.", "contents": "Studies on gamma-glutamyl transpeptidase in human and rabbit erythrocytes. Gamma-glutamyl transpeptidase transfers the gamma-glutamyl moiety of glutathione to a variety of acceptor amino acids. Through the operation of the gamma-glutamyl-cyclotransferase cycle, this enzyme has been implicated in the transport of amino acids into cells, especially the cells of the proximal tubules of kidney. It has been reported to be present in rabbit erythrocytes. However, using white cell-free preparations, we have not been able to demonstrate the presence of gamma-glutamyl transpeptidase in human or rabbit erythrocytes either by measuring the utilization of GSH or by following the formation of the product. 14C-L-methionine was used as acceptor amino acid, and the formation of gamma-glutamyl-14C-L-methionine was followed. Using similar conditions, we have been able to demonstrate the presence of gamma-glutamyl transpeptidase in human and rabbit leukocytes and in human kidney. In contrast to a previous report, we were unable to find the accumulation of 5-oxoproline, an intermediate of the gamma-glutamyl-cyclotransferase pathway in human red cells incubated in Krebs-Ringer solution. Immunologic studies demonstrated that human red cell membranes contained no protein antigenically similar to kidney gamma-glutamyl transpeptidase. Thus our studies indicated that in human and rabbit erythrocytes, the gamma-glutamyl transpeptidase-cyclotransferase pathway was not operative."}
{"id": "PMID:4176", "title": "The pH dependence of quantitative ristocetin-induced platelet aggregation: theoretical and practical implications-a new device for maintenance of platelet-rich plasma pH.", "content": "Quantitative ristocetin-induced platelet aggregation of normal platelet-rich plasma (PRP) decreased with time after PRP preparation. An increase in p H of the PRP with time proved to be responsible for this finding. Diffusion of CO2from the plasma is the prime determinant of the change in pH. Since a complex combination of factors influences CO2 diffusion (surface area-to-volume relationship, capping, mixing, etc.) The change in pH is variable with time. Thus, quantitative ristocetin aggregation should be pH controlled. A simple device for maintaining PRP pH constant by control of the ambient pCO2 was designed and found effective in keeping both pH and quantitative ristocetin aggregation constant over a prolonged period of time. It can be adapted for use in platelet aggregation studies employing other reagents. The pH dependence of ristocetin-induced platelet aggregation is consistent with other data supporting an elctrostatic interaction between the platelet, von Willebrand factor, and ristocetin. We favor a model wherein ristocetin neutralizes some of the platelet's negative change and permits the von Willebrand factor to bridge sites on separate platelets to induce agglutination.", "contents": "The pH dependence of quantitative ristocetin-induced platelet aggregation: theoretical and practical implications-a new device for maintenance of platelet-rich plasma pH. Quantitative ristocetin-induced platelet aggregation of normal platelet-rich plasma (PRP) decreased with time after PRP preparation. An increase in p H of the PRP with time proved to be responsible for this finding. Diffusion of CO2from the plasma is the prime determinant of the change in pH. Since a complex combination of factors influences CO2 diffusion (surface area-to-volume relationship, capping, mixing, etc.) The change in pH is variable with time. Thus, quantitative ristocetin aggregation should be pH controlled. A simple device for maintaining PRP pH constant by control of the ambient pCO2 was designed and found effective in keeping both pH and quantitative ristocetin aggregation constant over a prolonged period of time. It can be adapted for use in platelet aggregation studies employing other reagents. The pH dependence of ristocetin-induced platelet aggregation is consistent with other data supporting an elctrostatic interaction between the platelet, von Willebrand factor, and ristocetin. We favor a model wherein ristocetin neutralizes some of the platelet's negative change and permits the von Willebrand factor to bridge sites on separate platelets to induce agglutination."}
{"id": "PMID:4177", "title": "[Case of congenital megaurethra associated with bilateral renal hyperplasia].", "content": "Authors report a very rare malformation of the external genital organs in a male new-born who died 48 hours after birth. This malformation consisted in a total aplasia of the corpus cavernosum and bulbus penis with a fusiforme dilatation of the anterior urethra. The malformation was associated with an anal imperforation, bilateral cryptorchidism and renal hypoplasia.", "contents": "[Case of congenital megaurethra associated with bilateral renal hyperplasia]. Authors report a very rare malformation of the external genital organs in a male new-born who died 48 hours after birth. This malformation consisted in a total aplasia of the corpus cavernosum and bulbus penis with a fusiforme dilatation of the anterior urethra. The malformation was associated with an anal imperforation, bilateral cryptorchidism and renal hypoplasia."}
{"id": "PMID:4179", "title": "On the mechanism of action of clozapine on the adrenergic neurone.", "content": "1 The antipsychotic drug, clozapine, lowered noradrenaline and metaraminol (MA) concentrations in the rat heart. This action was blocked by the presence of a ganglionic blocking drug. 2 Other alpha-adrenoceptor blocking drugs (phenoxybenzamine, phentolamine) did not significantly lower heart amine concentrations. An inhibitor of neuronal amine uptake (desipramine) caused only a slight lowering. The combination of phentolamine and desipramine showed considerable activity, and this action was blocked by ganglionic blockade. 3 Clozapine had little or no action in blocking amine uptake, yet greatly potentiated amine release caused by the phentolamine-desipramine combination. 4 Other antipsychotic drugs (haloperidol, chlorpromazine, thioridazine) or other agents (propranolol, atropine) did not share this action of clozapine. 5 Ganglionic blockade markedly delayed amine release induced by reserpine administration. 6 It is suggested that clozapine may have an incomplete reserpine-like effect specifically on the adrenergic neurone, facilitating impulse-induced amine release.", "contents": "On the mechanism of action of clozapine on the adrenergic neurone. 1 The antipsychotic drug, clozapine, lowered noradrenaline and metaraminol (MA) concentrations in the rat heart. This action was blocked by the presence of a ganglionic blocking drug. 2 Other alpha-adrenoceptor blocking drugs (phenoxybenzamine, phentolamine) did not significantly lower heart amine concentrations. An inhibitor of neuronal amine uptake (desipramine) caused only a slight lowering. The combination of phentolamine and desipramine showed considerable activity, and this action was blocked by ganglionic blockade. 3 Clozapine had little or no action in blocking amine uptake, yet greatly potentiated amine release caused by the phentolamine-desipramine combination. 4 Other antipsychotic drugs (haloperidol, chlorpromazine, thioridazine) or other agents (propranolol, atropine) did not share this action of clozapine. 5 Ganglionic blockade markedly delayed amine release induced by reserpine administration. 6 It is suggested that clozapine may have an incomplete reserpine-like effect specifically on the adrenergic neurone, facilitating impulse-induced amine release."}
{"id": "PMID:4186", "title": "Effect of SAS (a new 10-N-acylaminophenothiazine) on gastric secretion and ulceration in rats.", "content": "The antiulcer and antisecretory activity of 2-chloro-10-[4'(N-beta-hydroxyethyl) piperazinyl-1'] acetylphenothiazine (SAS) has been investigated. At 10 and 20 mg/kg (s.c.) the drug was found to possess potent antigastric secretory and antiulcer activity (both in shay and stress ulcers) and did not exhibit any peripheral parasympathetic blocking activity. The pronounced antispasmodic activity of SAS was nonspecific rather than a specific parasympatholytic effect.", "contents": "Effect of SAS (a new 10-N-acylaminophenothiazine) on gastric secretion and ulceration in rats. The antiulcer and antisecretory activity of 2-chloro-10-[4'(N-beta-hydroxyethyl) piperazinyl-1'] acetylphenothiazine (SAS) has been investigated. At 10 and 20 mg/kg (s.c.) the drug was found to possess potent antigastric secretory and antiulcer activity (both in shay and stress ulcers) and did not exhibit any peripheral parasympathetic blocking activity. The pronounced antispasmodic activity of SAS was nonspecific rather than a specific parasympatholytic effect."}
{"id": "PMID:4187", "title": "Histamine H2-receptors in the human peripheral circulation.", "content": "Histamine (10 mug/min for 3 min) infused into the brachial artery caused an increase in forearm blood flow which was reduced by mepyramine (25 mg). This effect was most marked in the first minute of the infusion. Metiamide (25 mg) had no effect on the dilatation during the infusion but caused a quicker return of flow to the resting level. The response was abolished when both drugs were given in combination. It is concluded that the response is initiated mainly by stimulation of H1-receptors and maintained by H1- and H2-receptors; continued activity of H2-receptors may account for the slow return of flow to the pre-infusional level.", "contents": "Histamine H2-receptors in the human peripheral circulation. Histamine (10 mug/min for 3 min) infused into the brachial artery caused an increase in forearm blood flow which was reduced by mepyramine (25 mg). This effect was most marked in the first minute of the infusion. Metiamide (25 mg) had no effect on the dilatation during the infusion but caused a quicker return of flow to the resting level. The response was abolished when both drugs were given in combination. It is concluded that the response is initiated mainly by stimulation of H1-receptors and maintained by H1- and H2-receptors; continued activity of H2-receptors may account for the slow return of flow to the pre-infusional level."}
{"id": "PMID:4188", "title": "A trial of fenfluramine in the treatment of the chronic alcoholic patient.", "content": "In a double blind trial, 50 male chronic alcoholic patients were treated with either fenfluramine in a dose of 60 mg or 120 mg daily, or with identically prepared placebo tablets. Patients were interviewed on admission to the trial and then at four-weekly intervals for a period of one year and blood levels of delta-aminolaevulinic acid dehydratase (ALAD) and gamma-glutamyl transpeptidase (gammaGT) and fenfluramine were determined. The efficacy of fenfluramine at the two dose levels was compared with placebo on the basis of the number of lapses indicated by the clinical history and also by alterations in the biochemical indices. Twenty-seven patients completed the period of observation, there being 9 in each of the three groups. Those receiving 120 mg fenfluramine daily showed significantly fewer lapses than either of the other two groups (p less than 0-01) on biochemical but not on clinical criteria. Overall assessment revealed that 3 of the 9 patients receiving the high dose of fenfluramine had a good result during the period of the trial, but there were none in the 60 mg group or in those receiving placebo. More extensive trials of fenfluramine in the treatment of chronic alcoholism are indicated.", "contents": "A trial of fenfluramine in the treatment of the chronic alcoholic patient. In a double blind trial, 50 male chronic alcoholic patients were treated with either fenfluramine in a dose of 60 mg or 120 mg daily, or with identically prepared placebo tablets. Patients were interviewed on admission to the trial and then at four-weekly intervals for a period of one year and blood levels of delta-aminolaevulinic acid dehydratase (ALAD) and gamma-glutamyl transpeptidase (gammaGT) and fenfluramine were determined. The efficacy of fenfluramine at the two dose levels was compared with placebo on the basis of the number of lapses indicated by the clinical history and also by alterations in the biochemical indices. Twenty-seven patients completed the period of observation, there being 9 in each of the three groups. Those receiving 120 mg fenfluramine daily showed significantly fewer lapses than either of the other two groups (p less than 0-01) on biochemical but not on clinical criteria. Overall assessment revealed that 3 of the 9 patients receiving the high dose of fenfluramine had a good result during the period of the trial, but there were none in the 60 mg group or in those receiving placebo. More extensive trials of fenfluramine in the treatment of chronic alcoholism are indicated."}
{"id": "PMID:4189", "title": "Towards rational therapy with monoamine oxidase inhibitors.", "content": "A rational approach to the use of monoamine oxidase inhibitors (MAOIs) is outlined. Patients suitable for treatment cannot be classified adequately using conventional diagnostic labels. They include those with primary symptoms of hypochondriasis, agoraphobia and social phobias, irritability, somatic anxiety and anergia; those with primary depressed mood, guilt, ideas of reference and personality disorders seldom respond. There is great variation in the interval between the first administration of these drugs and clinical response, and this may account for the inconsistencies in published trials. The type of drug and its dose may affect rate of response, as may biochemical factors, including acetylator and monoamine oxidase status. To obtain maximum benefit, a course of therapy with MAOIs should last for several months.", "contents": "Towards rational therapy with monoamine oxidase inhibitors. A rational approach to the use of monoamine oxidase inhibitors (MAOIs) is outlined. Patients suitable for treatment cannot be classified adequately using conventional diagnostic labels. They include those with primary symptoms of hypochondriasis, agoraphobia and social phobias, irritability, somatic anxiety and anergia; those with primary depressed mood, guilt, ideas of reference and personality disorders seldom respond. There is great variation in the interval between the first administration of these drugs and clinical response, and this may account for the inconsistencies in published trials. The type of drug and its dose may affect rate of response, as may biochemical factors, including acetylator and monoamine oxidase status. To obtain maximum benefit, a course of therapy with MAOIs should last for several months."}
{"id": "PMID:4190", "title": "Urinary gamma-glutamyl transpeptidase, an indicator of renal ischaemic injury and homograft rejection.", "content": "Gammaglutamyl transpeptidase is an enzyme primarily located in the brush border of the proximal convoluted tubules of the kidney. Its unique localisation in the renal cells most easily damaged by ischaemia and its ease of assay provides the rationale for its use in the measurement of renal ischaemic injury. Using a standard experimental animal model, canine urinary gamma-GT activity was shown to be increased up to 70-fold following 90 min of unilateral renal ischaemia and was significantly raised following only 5 min ischaemia. The urinary gamma-GT was used as a measure of ischaemic injury associated with renal transplantation in man and 20 consecutive patients undergoing kidney transplant were studied by daily 24-hour urinary gamma-GT estimations and excellent correlation was obtained between raised enzyme activity and the clinical diagnosis of transplant rejection.", "contents": "Urinary gamma-glutamyl transpeptidase, an indicator of renal ischaemic injury and homograft rejection. Gammaglutamyl transpeptidase is an enzyme primarily located in the brush border of the proximal convoluted tubules of the kidney. Its unique localisation in the renal cells most easily damaged by ischaemia and its ease of assay provides the rationale for its use in the measurement of renal ischaemic injury. Using a standard experimental animal model, canine urinary gamma-GT activity was shown to be increased up to 70-fold following 90 min of unilateral renal ischaemia and was significantly raised following only 5 min ischaemia. The urinary gamma-GT was used as a measure of ischaemic injury associated with renal transplantation in man and 20 consecutive patients undergoing kidney transplant were studied by daily 24-hour urinary gamma-GT estimations and excellent correlation was obtained between raised enzyme activity and the clinical diagnosis of transplant rejection."}
{"id": "PMID:4193", "title": "Neutrophil pyruvate kinase deficiency with recurrent staphylococcal infections: first reported case.", "content": "A woman with an intracellular killing defect in the neutrophils had neutrophil pyruvate kinase deficiency. She had had recurrent staphylococcal infections throughout her life. The enzyme present was unstable and its kinetics were abnormal.", "contents": "Neutrophil pyruvate kinase deficiency with recurrent staphylococcal infections: first reported case. A woman with an intracellular killing defect in the neutrophils had neutrophil pyruvate kinase deficiency. She had had recurrent staphylococcal infections throughout her life. The enzyme present was unstable and its kinetics were abnormal."}
{"id": "PMID:4197", "title": "Tyrosine hydroxylase and dopamine-beta-hydroxylase: distribution in discrete areas of the rat limbic system.", "content": "Tyrosine hydroxylase and dopamine-beta-hydroxylase have been measured in 34 discrete areas and nuclei of the limbic system of the rat. Both enzymes showed an uneven distribution in this system. The ratio between tyrosine hydroxylase and dopamine-beta-hydroxylase activities showed a significant correlation when compared with the ratio of dopamine and norepinephrine concentrations for the areas studied. The results strongly suggest that dopaminergic terminals are present in discrete areas of the limbic cortex, and several septal and amygdaloid nuclei, and allow the precise localization of dopaminergic and noradrenergic areas in the limbic system.", "contents": "Tyrosine hydroxylase and dopamine-beta-hydroxylase: distribution in discrete areas of the rat limbic system. Tyrosine hydroxylase and dopamine-beta-hydroxylase have been measured in 34 discrete areas and nuclei of the limbic system of the rat. Both enzymes showed an uneven distribution in this system. The ratio between tyrosine hydroxylase and dopamine-beta-hydroxylase activities showed a significant correlation when compared with the ratio of dopamine and norepinephrine concentrations for the areas studied. The results strongly suggest that dopaminergic terminals are present in discrete areas of the limbic cortex, and several septal and amygdaloid nuclei, and allow the precise localization of dopaminergic and noradrenergic areas in the limbic system."}
{"id": "PMID:4199", "title": "Resolution, specificity and transphosphorylase activity of calcifying cartilage alkaline phosphatases.", "content": "The phosphate releasing activity from calf scapula cartilage was resolved by DEAE-cellulose chromatography into two distinct phosphatase activities. The activity eluted first from the column (phosphatase I) was active towards a variety of phosphate esters and several linear oligo phosphates including sodium pyrophosphate, while the second phosphatase activity (phosphatase II) was active only towards simple phosphate esters. Phosphatase I acted towards oligo phosphates in a stepwise fashion hydrolyzing one phosphate at a time. Both phosphatase are sialoproteins and can transfer phosphate from any of their substrates into other than water phosphate acceptor molecules such as glycerol. By several criteria, it can be concluded that the two phosphatases are different enzyme entities.", "contents": "Resolution, specificity and transphosphorylase activity of calcifying cartilage alkaline phosphatases. The phosphate releasing activity from calf scapula cartilage was resolved by DEAE-cellulose chromatography into two distinct phosphatase activities. The activity eluted first from the column (phosphatase I) was active towards a variety of phosphate esters and several linear oligo phosphates including sodium pyrophosphate, while the second phosphatase activity (phosphatase II) was active only towards simple phosphate esters. Phosphatase I acted towards oligo phosphates in a stepwise fashion hydrolyzing one phosphate at a time. Both phosphatase are sialoproteins and can transfer phosphate from any of their substrates into other than water phosphate acceptor molecules such as glycerol. By several criteria, it can be concluded that the two phosphatases are different enzyme entities."}
{"id": "PMID:4200", "title": "Testosterone metabolism in male rat epiphysis.", "content": "Using radioactive substrate, thin-layer chromatography and recrystallization methods as well as differential centrifugation, gel filtration and electrophoresis, testosterone metabolism was investigated in male rat epiphyseal growth plate. 5alpha-androstane 3alpha-17beta-diol was found to be a major metabolite in vitro; lesser amounts of androstenedione and androstanedione, and a very small amount of 5alpha-dihydrotestosterone were also identified. Radioactivity was recovered in epiphyseal subcellular fractions 30 minutes following in vivo administration of tritiated 5alpha-dihydrotestosterone; within 2 hours radioactivity had fallen to essentially background level in all fractions but the cytosol. A testosterone binding protein could not be identified within epiphyseal cytosol.", "contents": "Testosterone metabolism in male rat epiphysis. Using radioactive substrate, thin-layer chromatography and recrystallization methods as well as differential centrifugation, gel filtration and electrophoresis, testosterone metabolism was investigated in male rat epiphyseal growth plate. 5alpha-androstane 3alpha-17beta-diol was found to be a major metabolite in vitro; lesser amounts of androstenedione and androstanedione, and a very small amount of 5alpha-dihydrotestosterone were also identified. Radioactivity was recovered in epiphyseal subcellular fractions 30 minutes following in vivo administration of tritiated 5alpha-dihydrotestosterone; within 2 hours radioactivity had fallen to essentially background level in all fractions but the cytosol. A testosterone binding protein could not be identified within epiphyseal cytosol."}
{"id": "PMID:4201", "title": "Studies related to antitumor antibiotics. Part V. Reactions of mitomycin C with DNA examined by ethidium fluorescence assay.", "content": "The cytotoxic action of the antitumor antibiotic mitomycin C occurs primarily at the level of DNA. Using highly sensitive fluorescence assays which depend on the enhancement of ethidium fluorescence only when it intercalates duplex regions of DNA, three aspects of mitomycin C action on DNA have been studied: (a) cross-linking events, (b) alkylation without necessarily cross-linking, and (c) strand breakage. Cross-linking of DNA is determined by the return of fluorescence after a heat denaturation step at alkaline pH's. Under these conditions denatured DNA gives no fluorescence. The cross-linking was independently confirmed by S1-endonuclease (EC 3.1.4.-) digestion. At relatively high concentrations of mitomycin the suppression of ethidium fluorescence enhancement was shown not to be due to depurination but rather to alkylation, as a result of losses in potential intercalation sites. A linear relationship exists between binding ratio for mitomycin and loss of fluorescence. The proportional decrease in fluorescence with pH strongly suggests that the alkylation is due to the aziridine moiety of the antibiotic under these conditions. A parallel increase in the rate and overall efficiency of covalent cross-linking of DNA with lower pH suggests that the cross-linking event, to which the primary cytotoxic action has been linked, occurs sequentially with alkylation by aziridine and then by carbamate. Mitomycin C, reduced chemically, was shown to induce single strand cleavage as well as monoaklylation and covalent cross-linking in PM2 covalently closed circular DNA. The inhibition of this cleavage by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6), and by free radical scavengers suggests that the degradation of DNA observed to accompany the cytotoxic action of mitomycin C is largely due to the free radical O2. In contrast to the behavior of the antibiotic streptonigrin, mitomycin C does not inactivate the protective enzymes superoxide dismutase or catalase. Lastly, mitomycin C is able to cross-link DNA in the absence of reduction at pH 4. This is consistent with the postulated cross-linking mechansims.", "contents": "Studies related to antitumor antibiotics. Part V. Reactions of mitomycin C with DNA examined by ethidium fluorescence assay. The cytotoxic action of the antitumor antibiotic mitomycin C occurs primarily at the level of DNA. Using highly sensitive fluorescence assays which depend on the enhancement of ethidium fluorescence only when it intercalates duplex regions of DNA, three aspects of mitomycin C action on DNA have been studied: (a) cross-linking events, (b) alkylation without necessarily cross-linking, and (c) strand breakage. Cross-linking of DNA is determined by the return of fluorescence after a heat denaturation step at alkaline pH's. Under these conditions denatured DNA gives no fluorescence. The cross-linking was independently confirmed by S1-endonuclease (EC 3.1.4.-) digestion. At relatively high concentrations of mitomycin the suppression of ethidium fluorescence enhancement was shown not to be due to depurination but rather to alkylation, as a result of losses in potential intercalation sites. A linear relationship exists between binding ratio for mitomycin and loss of fluorescence. The proportional decrease in fluorescence with pH strongly suggests that the alkylation is due to the aziridine moiety of the antibiotic under these conditions. A parallel increase in the rate and overall efficiency of covalent cross-linking of DNA with lower pH suggests that the cross-linking event, to which the primary cytotoxic action has been linked, occurs sequentially with alkylation by aziridine and then by carbamate. Mitomycin C, reduced chemically, was shown to induce single strand cleavage as well as monoaklylation and covalent cross-linking in PM2 covalently closed circular DNA. The inhibition of this cleavage by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6), and by free radical scavengers suggests that the degradation of DNA observed to accompany the cytotoxic action of mitomycin C is largely due to the free radical O2. In contrast to the behavior of the antibiotic streptonigrin, mitomycin C does not inactivate the protective enzymes superoxide dismutase or catalase. Lastly, mitomycin C is able to cross-link DNA in the absence of reduction at pH 4. This is consistent with the postulated cross-linking mechansims."}
{"id": "PMID:4202", "title": "Acid proteases from species of Mucor. III. Interaction with concanavalin A and concanavalin A Sepharose.", "content": "The reaction of Mucor miehei protease with concanavalin A was followed by a turbidimetric assay in the pH range 5-8. At pH 4.0, no turbidity developed but binding of the enzyme to concanavalin A could be demonstrated by gel filtration. Two fractions of apparent molecular weight 65000 and 52000 were isolated, the 65000 molecular weight species apparently representing a protomer of concanavalin A (24000) bound to the enzyme. An analysis of the circular dichroism spectrum of this complex suggested that protomer binding results in a conformational change in the enzyme which is associated with a 30% increase in proteolytic activity. At pH 6.0, the enzyme was strongly bound to columns of concanavalin A Sepharose but could be removed by including alpha-methyl D-glucoside and NaC1 in the elution buffer. Some column degradation occurred at room temperature but was not detectable at 4 degrees C where rapid elution of the enzyme resulted in a greater than 90% yield of highly active protein. Periodate-oxidized Mucor miehei protease and Mucor renin did not react with concanavalin A and were not bound to the affinity column.", "contents": "Acid proteases from species of Mucor. III. Interaction with concanavalin A and concanavalin A Sepharose. The reaction of Mucor miehei protease with concanavalin A was followed by a turbidimetric assay in the pH range 5-8. At pH 4.0, no turbidity developed but binding of the enzyme to concanavalin A could be demonstrated by gel filtration. Two fractions of apparent molecular weight 65000 and 52000 were isolated, the 65000 molecular weight species apparently representing a protomer of concanavalin A (24000) bound to the enzyme. An analysis of the circular dichroism spectrum of this complex suggested that protomer binding results in a conformational change in the enzyme which is associated with a 30% increase in proteolytic activity. At pH 6.0, the enzyme was strongly bound to columns of concanavalin A Sepharose but could be removed by including alpha-methyl D-glucoside and NaC1 in the elution buffer. Some column degradation occurred at room temperature but was not detectable at 4 degrees C where rapid elution of the enzyme resulted in a greater than 90% yield of highly active protein. Periodate-oxidized Mucor miehei protease and Mucor renin did not react with concanavalin A and were not bound to the affinity column."}
{"id": "PMID:4203", "title": "Physical, chemical, and enzymatic studies on the major sucrase of honey bees (Apis mellifera).", "content": "A sucrase from honey bees (Apis mellifera) which precipitates between ammonium sulfate saturations of 50 and 70% (5 mg protein per millilitre) and which makes up the major portion of the sucrases of honey bees was purified to homogeneity as shown by several criteria. A large part of the sucrase was found in the head while most of the rest was in the abdomen (a small amount was in the thorax). The enzyme precipitated between the same values of ammonium sulfate saturation as did the sucrase in honey and honey sucrase exhibited kinetics very similar to those of this enzyme. The enzyme was found to be a relatively nonspecific alpha-glucosidase and was shown to have transglucosidase activity. The production of glucose from sucrose was rectilinear when plotted by the Hofstee method at low substrate concentrations but decreased at high sucrose concentrations. The production of fructose was rectilinear throughout the concentration range used. The production of both glucose and rho-nitrophenol when rho nitrophenyl alpha-D-glucoside was the substrate was linear by the Hofstee plot. These effects were found to be due to transglucolysis and a mechanism of action is proposed. Amino acid and amino sugar analyses indicated that the sucrase was a glycoprotein. The molecular weight was found to be between 51000 and 82000 by three different methods and an so20.w value of 4.0 S was obtained. There was no evidence for subunit structure. Tests of the enzyme under various denaturation conditions did not reveal any unusual stabilities. The sucrase bound very tightly to a hydrophobic column. Iodoacetic acid decreased the activity of the sucrase but a large concentration was needed to bring about a 50% activity loss. Reducing agents caused some activity declines. Diethyl pyrocarbonate activated the enzyme.", "contents": "Physical, chemical, and enzymatic studies on the major sucrase of honey bees (Apis mellifera). A sucrase from honey bees (Apis mellifera) which precipitates between ammonium sulfate saturations of 50 and 70% (5 mg protein per millilitre) and which makes up the major portion of the sucrases of honey bees was purified to homogeneity as shown by several criteria. A large part of the sucrase was found in the head while most of the rest was in the abdomen (a small amount was in the thorax). The enzyme precipitated between the same values of ammonium sulfate saturation as did the sucrase in honey and honey sucrase exhibited kinetics very similar to those of this enzyme. The enzyme was found to be a relatively nonspecific alpha-glucosidase and was shown to have transglucosidase activity. The production of glucose from sucrose was rectilinear when plotted by the Hofstee method at low substrate concentrations but decreased at high sucrose concentrations. The production of fructose was rectilinear throughout the concentration range used. The production of both glucose and rho-nitrophenol when rho nitrophenyl alpha-D-glucoside was the substrate was linear by the Hofstee plot. These effects were found to be due to transglucolysis and a mechanism of action is proposed. Amino acid and amino sugar analyses indicated that the sucrase was a glycoprotein. The molecular weight was found to be between 51000 and 82000 by three different methods and an so20.w value of 4.0 S was obtained. There was no evidence for subunit structure. Tests of the enzyme under various denaturation conditions did not reveal any unusual stabilities. The sucrase bound very tightly to a hydrophobic column. Iodoacetic acid decreased the activity of the sucrase but a large concentration was needed to bring about a 50% activity loss. Reducing agents caused some activity declines. Diethyl pyrocarbonate activated the enzyme."}
{"id": "PMID:4204", "title": "Studies on the formation by rat brain preparations of CDP-diglyceride from CTP and phosphatidic acids of varying fatty acid compositions.", "content": "The enzyme, CTP:phosphatidate cytidylyltransferase (EC2.7.7.41) which catalyses formation of CDP-diglyceride from CTP and phosphatidic acid has been studied in rat brain preparations and other tissues. Improvement, as judged by the higher tissue activities obtained, in the assay method for this enzyme was achieved through use of phosphatidic acids sonicated in buffer-detergent solution saturated with ether and containing bovine serum albumin and use of short incubation times which essentially provided a measure of initial rates. The enzyme of rat brain microsomes yielded with 1,2-dioleolphosphatidic acid as substrate a pH optimum of 6.8 with maleate buffer and optimal concentrations of 60mM for MG2+, 6MM for CTP and 250 mug per 0.8 ml for phosphatidic acid. Enzyme activity was mainly located in the 90,000 X g fraction (microsomal) with small but significant activity in the 12,000 X g fraction. Comparison of activities (nanomoles CTP incorporated per milligram protein per minute) amongst tissues showed the following order: brain, 1.87; liver, 1.32; lung, 1.19; small intestine, 1.00; kidney, 0.69; heart, 0.41; diaphragm, 0.07; skeletal muscle, 0.02. Examination of the effect of varying the fatty acid composition in the phosphatidic acids added exogenously gave the following order (activities in parentheses); 1-stearoyl-2-oleoyl- (5.58), 1-oleoyl-2-stearoyl- (5.37), 1,2-dioleoyl- (4.49) 1-palmitoyl-2-oleoyl-(3.85), 1-stearoyl-2-arachidonoyl-(3.31), 1-arachidonoyl-2-stearoyl-(3.16), 1,2-diarachidonoyl-(0.72), 1,2-dicaproyl-(0.67), 1,2-dipalmitoyl-(0.67) and 1,2-distearoyl-(0.18). The single bis- and lysophosphatidic acids tested were inactive as substrates. Apart from a possible preference for one or more unsaturated fatty acids the transferase enzyme showed no selectivity in respect to the fatty acid distribution of phosphatidic acids.", "contents": "Studies on the formation by rat brain preparations of CDP-diglyceride from CTP and phosphatidic acids of varying fatty acid compositions. The enzyme, CTP:phosphatidate cytidylyltransferase (EC2.7.7.41) which catalyses formation of CDP-diglyceride from CTP and phosphatidic acid has been studied in rat brain preparations and other tissues. Improvement, as judged by the higher tissue activities obtained, in the assay method for this enzyme was achieved through use of phosphatidic acids sonicated in buffer-detergent solution saturated with ether and containing bovine serum albumin and use of short incubation times which essentially provided a measure of initial rates. The enzyme of rat brain microsomes yielded with 1,2-dioleolphosphatidic acid as substrate a pH optimum of 6.8 with maleate buffer and optimal concentrations of 60mM for MG2+, 6MM for CTP and 250 mug per 0.8 ml for phosphatidic acid. Enzyme activity was mainly located in the 90,000 X g fraction (microsomal) with small but significant activity in the 12,000 X g fraction. Comparison of activities (nanomoles CTP incorporated per milligram protein per minute) amongst tissues showed the following order: brain, 1.87; liver, 1.32; lung, 1.19; small intestine, 1.00; kidney, 0.69; heart, 0.41; diaphragm, 0.07; skeletal muscle, 0.02. Examination of the effect of varying the fatty acid composition in the phosphatidic acids added exogenously gave the following order (activities in parentheses); 1-stearoyl-2-oleoyl- (5.58), 1-oleoyl-2-stearoyl- (5.37), 1,2-dioleoyl- (4.49) 1-palmitoyl-2-oleoyl-(3.85), 1-stearoyl-2-arachidonoyl-(3.31), 1-arachidonoyl-2-stearoyl-(3.16), 1,2-diarachidonoyl-(0.72), 1,2-dicaproyl-(0.67), 1,2-dipalmitoyl-(0.67) and 1,2-distearoyl-(0.18). The single bis- and lysophosphatidic acids tested were inactive as substrates. Apart from a possible preference for one or more unsaturated fatty acids the transferase enzyme showed no selectivity in respect to the fatty acid distribution of phosphatidic acids."}
{"id": "PMID:4205", "title": "Effect of metiamide on acid secretion from isolated kitten fundic mucosa.", "content": "Isolated kitten fundic mucosa demonstrates low rates of spontaneous acid secretion in vitro when bathed in Krebs-Henseleit solution, and responds consistently to histamine, pentagastrin, and acetylcholine placed in the bath. High rates of spontaneous secretion or secretion in response to histamine and pentagastrin were significantly inhibited by addition of metiamide (5 X 10(-3) M); but mucosa stimulated by constant addition of acetylcholine chloride (10(-4) M) was not inhibited by metiamide at the same concentration.", "contents": "Effect of metiamide on acid secretion from isolated kitten fundic mucosa. Isolated kitten fundic mucosa demonstrates low rates of spontaneous acid secretion in vitro when bathed in Krebs-Henseleit solution, and responds consistently to histamine, pentagastrin, and acetylcholine placed in the bath. High rates of spontaneous secretion or secretion in response to histamine and pentagastrin were significantly inhibited by addition of metiamide (5 X 10(-3) M); but mucosa stimulated by constant addition of acetylcholine chloride (10(-4) M) was not inhibited by metiamide at the same concentration."}
{"id": "PMID:4206", "title": "Myoplasmic impedance of the barnacle muscle fiber.", "content": "Myoplasmic impedance was measured on a barnacle (Balanus nubilus) single muscle fiber that was placed in a cylindrical cavity to limit the volume and prevent the hydration of the myoplasm. At both ends of the cavity, the myoplasm was in direct contact with an electrolyte solution. When equilibrium with the external medium was reached, the myoplasmic impedance was measured at 10 degrees C with an impedance bridge at 1000 Hz. The results indicated that the myoplasmic impedance of the muscle fiber is mainly resistive. Treating the myoplasm as a suspension of small conductive particles, we deduced the specific conductivity of the contractile filaments kf and their volume fraction rho (kf = 2.78 X 10(-3) omega-1cm-1, and rho = 0.48). The experimental technique permits an estimate of the specific myoplasmic conductivity in vivo (6.27 X 10(-3) omega-1cm-1). Finally, a decrease in the pH of the external solution from 10.1 to 4.0 lowered the myoplasmic conductivity by 16%. This may be considered as indirect evidence that the conductivity of the contractile filaments is associated with the protein counter-ions, since Hinke et al. (1973. Ann. N.Y. Acad. Sci. 204, 274-296.) reported evidence that a lowering of pH decreases the number of counter-ions.", "contents": "Myoplasmic impedance of the barnacle muscle fiber. Myoplasmic impedance was measured on a barnacle (Balanus nubilus) single muscle fiber that was placed in a cylindrical cavity to limit the volume and prevent the hydration of the myoplasm. At both ends of the cavity, the myoplasm was in direct contact with an electrolyte solution. When equilibrium with the external medium was reached, the myoplasmic impedance was measured at 10 degrees C with an impedance bridge at 1000 Hz. The results indicated that the myoplasmic impedance of the muscle fiber is mainly resistive. Treating the myoplasm as a suspension of small conductive particles, we deduced the specific conductivity of the contractile filaments kf and their volume fraction rho (kf = 2.78 X 10(-3) omega-1cm-1, and rho = 0.48). The experimental technique permits an estimate of the specific myoplasmic conductivity in vivo (6.27 X 10(-3) omega-1cm-1). Finally, a decrease in the pH of the external solution from 10.1 to 4.0 lowered the myoplasmic conductivity by 16%. This may be considered as indirect evidence that the conductivity of the contractile filaments is associated with the protein counter-ions, since Hinke et al. (1973. Ann. N.Y. Acad. Sci. 204, 274-296.) reported evidence that a lowering of pH decreases the number of counter-ions."}
{"id": "PMID:4207", "title": "Pulmonary edema and ascorbic acid loss.", "content": "Loss of ascorbic acid from lung and pulmonary edema were produced in mice by intravenous injection of either adrenaline or noradrenaline (5 mumol/kg). While adrenalectomy performed before noradrenaline administration reduced the degree of pulmonary edema, a prior dose of hexamethonium accentuated this effect. Given alone, hexamethonium caused both loss of ascorbic acid and pulmonary edema. The results show that although endogenous catecholamines can potentiate the pulmonary edema produced by either adrenaline or noradrenaline, they play no specific role in the ascorbic acid loss. The evidence suggests that lung ascorbic acid levels are decreased following the development of pulmonary edema, irrespective of how it was caused.", "contents": "Pulmonary edema and ascorbic acid loss. Loss of ascorbic acid from lung and pulmonary edema were produced in mice by intravenous injection of either adrenaline or noradrenaline (5 mumol/kg). While adrenalectomy performed before noradrenaline administration reduced the degree of pulmonary edema, a prior dose of hexamethonium accentuated this effect. Given alone, hexamethonium caused both loss of ascorbic acid and pulmonary edema. The results show that although endogenous catecholamines can potentiate the pulmonary edema produced by either adrenaline or noradrenaline, they play no specific role in the ascorbic acid loss. The evidence suggests that lung ascorbic acid levels are decreased following the development of pulmonary edema, irrespective of how it was caused."}
{"id": "PMID:4208", "title": "Development of amino acid uptake activity in Neurospora.", "content": "During the germination and growth of Neurospora conidia, amino acid permease systems I (neutral) and II (general) increase in specific activity. System III (basic) decreases in specific activity with the onset of germination. System I shows two peaks of activity during the logarithmic phase of growth. One peak occurs at 6 h, the other at 12 h of growth. Both peaks are abolished in the mtr mutant. Both peaks have a Km for phenylalanine of 40 muM. The peaks of system I activity appear to correlate with morphological changes.", "contents": "Development of amino acid uptake activity in Neurospora. During the germination and growth of Neurospora conidia, amino acid permease systems I (neutral) and II (general) increase in specific activity. System III (basic) decreases in specific activity with the onset of germination. System I shows two peaks of activity during the logarithmic phase of growth. One peak occurs at 6 h, the other at 12 h of growth. Both peaks are abolished in the mtr mutant. Both peaks have a Km for phenylalanine of 40 muM. The peaks of system I activity appear to correlate with morphological changes."}
{"id": "PMID:4209", "title": "Production, purification and characterization of thermomycolase, the extracellular serine protease of the thermophilic fungus Malbranchea pulchella var. sulfurea.", "content": "The thermophilic fungus Malbranchea pulchella produces a single extracellular, alkaline, serine protease when grown at 45 degrees C, on 2% casein as sole carbon source. The growth-associated production of protease in submerged cultures was inhibited by addition of glucose, amino acids, or yeast extract. A simple four-step purification which yields homogeneous protease in 78% yield is described. The protease has an isoelectric point of 6.0, a pH optimum of 8.5, and is completely inhibited by serine protease inhibitors. A specificity study with small synthetic ester substrates indicated that the protease preferentially hydrolyzed bonds situated on the carboxyl side of aromatic or apolar amino acid residues which are not beta-branched, positively charged or of the D configuration. Peptidase substrates and others such as N-acetyl-L-tyrosine-ethyl ester were not hydrolyzed. The protease was stable over a broad range of pH (6.5-9.5 at 30 degrees C, 20 h), and was particularly thermostable (t1/2 = 110 min at 73 degrees C, pH 7.4) in the presence of Ca2+ (10 mM). Macromolecules and Ca2+ also provide protection against the significant autolysis which occurs at pure protease concentrations greater than 0.01 mg/mo, as well as against surface denaturation which is enhanced by the presence of a silicone antifoam agent. Hence the stability of protease in submerged cultures is rationalized.", "contents": "Production, purification and characterization of thermomycolase, the extracellular serine protease of the thermophilic fungus Malbranchea pulchella var. sulfurea. The thermophilic fungus Malbranchea pulchella produces a single extracellular, alkaline, serine protease when grown at 45 degrees C, on 2% casein as sole carbon source. The growth-associated production of protease in submerged cultures was inhibited by addition of glucose, amino acids, or yeast extract. A simple four-step purification which yields homogeneous protease in 78% yield is described. The protease has an isoelectric point of 6.0, a pH optimum of 8.5, and is completely inhibited by serine protease inhibitors. A specificity study with small synthetic ester substrates indicated that the protease preferentially hydrolyzed bonds situated on the carboxyl side of aromatic or apolar amino acid residues which are not beta-branched, positively charged or of the D configuration. Peptidase substrates and others such as N-acetyl-L-tyrosine-ethyl ester were not hydrolyzed. The protease was stable over a broad range of pH (6.5-9.5 at 30 degrees C, 20 h), and was particularly thermostable (t1/2 = 110 min at 73 degrees C, pH 7.4) in the presence of Ca2+ (10 mM). Macromolecules and Ca2+ also provide protection against the significant autolysis which occurs at pure protease concentrations greater than 0.01 mg/mo, as well as against surface denaturation which is enhanced by the presence of a silicone antifoam agent. Hence the stability of protease in submerged cultures is rationalized."}
{"id": "PMID:4210", "title": "Biosynthesis of chloramphenicol in Streptomyces sp. 3022a. Identification of p-amino-L-phenylalanine as a product from the action of arylamine synthetase on chorismic acid.", "content": "Products obtained from the action of arylamine synthetase on [G-14C]chorismic acid were fractionated by gel filtration and ion exchange column chromatography to yield a partially purified radioactive component with an arylamine function. From its ultraviolet absorption spectrum and thin-layer chromatographic behaviour the product was considered to be p-aminophenylalanine and the identification was confirmed by co-crystallization with an authentic specimen. Specific deamination of the product with L-amino-acid oxidase indicated that it was the L-epimer. These results strengthen previous evidence that arylamine synthetase is at a branch point in the shikimic acid pathway, specifically diverting intermediates to the synthesis of chloramphenicol.", "contents": "Biosynthesis of chloramphenicol in Streptomyces sp. 3022a. Identification of p-amino-L-phenylalanine as a product from the action of arylamine synthetase on chorismic acid. Products obtained from the action of arylamine synthetase on [G-14C]chorismic acid were fractionated by gel filtration and ion exchange column chromatography to yield a partially purified radioactive component with an arylamine function. From its ultraviolet absorption spectrum and thin-layer chromatographic behaviour the product was considered to be p-aminophenylalanine and the identification was confirmed by co-crystallization with an authentic specimen. Specific deamination of the product with L-amino-acid oxidase indicated that it was the L-epimer. These results strengthen previous evidence that arylamine synthetase is at a branch point in the shikimic acid pathway, specifically diverting intermediates to the synthesis of chloramphenicol."}
{"id": "PMID:4211", "title": "Uptake and efflux of succinic acid by uninduced mycelium of Claviceps purpurea.", "content": "Claviceps purpurea PRL 1980 grew on partially dissociated succinic acid (pH 4) but not on fully dissociated succinic acid (pH 7.2). Myeclium suspended in 42 mM solution of partially ionized succinic acid (pH 4; 60.1% nonionized, 39% monoanion, and 0.9% dianion, K+ salt) over a period of 25 min accumulated more succinic acid carbon than mycelium suspended in highly ionized solution (pH 6.8; 0.01% nonionized, 4.8% monoanion, and 95% dianion). The greater accumulation from partially ionized solution was not attributable solely to metabolism of succinic acid nor to the lower external concentration of potassium ion. Rate of uptake by sodium azide and iodoacetate-treated mycelium was proportional to external concentration at least up to 200 mumol/ml. External potassium or sodium ion was not required for uptake by inhibited or uninhibited mycelium and external sodium ion and glucose did not allow concentration of succinic acid. The internal concentrations of succinic acid carbon expressed as succinic acid in cell water were about the same as the external concentrations. Uptake was not appreciably affected by extent of ionization of external succinic acid but accumulation was markedly affected. A plot of accumulated succinic acid carbon against external pH produced a bimodal curve with the two maxima corresponding to the maximal concentrations of nonionized and monoanion succinic acid. The bimodal curve probably results from overlapping of two separate curves; the nonionized form accumulating efficiently because of one interaction with the cell and the monoanion form accumulating efficiently because of another interaction. Uptake from concentrated solution is by diffusion and efflux is rapid but not complete. Efflux is not retarded by presence of phosphate in the external solution.", "contents": "Uptake and efflux of succinic acid by uninduced mycelium of Claviceps purpurea. Claviceps purpurea PRL 1980 grew on partially dissociated succinic acid (pH 4) but not on fully dissociated succinic acid (pH 7.2). Myeclium suspended in 42 mM solution of partially ionized succinic acid (pH 4; 60.1% nonionized, 39% monoanion, and 0.9% dianion, K+ salt) over a period of 25 min accumulated more succinic acid carbon than mycelium suspended in highly ionized solution (pH 6.8; 0.01% nonionized, 4.8% monoanion, and 95% dianion). The greater accumulation from partially ionized solution was not attributable solely to metabolism of succinic acid nor to the lower external concentration of potassium ion. Rate of uptake by sodium azide and iodoacetate-treated mycelium was proportional to external concentration at least up to 200 mumol/ml. External potassium or sodium ion was not required for uptake by inhibited or uninhibited mycelium and external sodium ion and glucose did not allow concentration of succinic acid. The internal concentrations of succinic acid carbon expressed as succinic acid in cell water were about the same as the external concentrations. Uptake was not appreciably affected by extent of ionization of external succinic acid but accumulation was markedly affected. A plot of accumulated succinic acid carbon against external pH produced a bimodal curve with the two maxima corresponding to the maximal concentrations of nonionized and monoanion succinic acid. The bimodal curve probably results from overlapping of two separate curves; the nonionized form accumulating efficiently because of one interaction with the cell and the monoanion form accumulating efficiently because of another interaction. Uptake from concentrated solution is by diffusion and efflux is rapid but not complete. Efflux is not retarded by presence of phosphate in the external solution."}
{"id": "PMID:4212", "title": "Characterization of a nitrogen-fixing bacterial strain from the roots of Digitaria sanguinalis.", "content": "Rates of nitrogen fixation of 3 to 10 g of N2 fixed per hectare per day were associated with root systems of Digitaria sanguinalis. A Gram-negative motile aerobic bacterial strain that was capable of N2 fixation was isolated from a washed root sample of one of these plants. Optimal growth and N2 fixation occurred at a pH of about 6.5, a temperature of 30-37 degrees C, and at a pO2 of about 0.01 atm. Increased rates of N2 fixation resulted when this strain was grown in mixed cultures with aerobic or facultative bacteria. Observations of cellular and cultural morphology and results of biochemical and physiological studies indicate that the isolate may be related to the Azotobacteraceae but that it is not identical with any of the members of this family. The importance of N2 fixation by this isolate in nature is unknown.", "contents": "Characterization of a nitrogen-fixing bacterial strain from the roots of Digitaria sanguinalis. Rates of nitrogen fixation of 3 to 10 g of N2 fixed per hectare per day were associated with root systems of Digitaria sanguinalis. A Gram-negative motile aerobic bacterial strain that was capable of N2 fixation was isolated from a washed root sample of one of these plants. Optimal growth and N2 fixation occurred at a pH of about 6.5, a temperature of 30-37 degrees C, and at a pO2 of about 0.01 atm. Increased rates of N2 fixation resulted when this strain was grown in mixed cultures with aerobic or facultative bacteria. Observations of cellular and cultural morphology and results of biochemical and physiological studies indicate that the isolate may be related to the Azotobacteraceae but that it is not identical with any of the members of this family. The importance of N2 fixation by this isolate in nature is unknown."}
{"id": "PMID:4213", "title": "Beta-glucanases in the yeast Cryptococcus albidus var. aerius. Production and separation of beta-glucanases in asynchronous cultures.", "content": "beta-Glucanases were detected in cell-free extracts of the yeast Cryptococcus albidus var. aerius when grown on glucose as the sole carbon source. The production of beta-glucanases was followed in log-phase cells and stationary-phase cells; the maximal production of beta-(1 leads to 3) and beta-(1 leads to 6) glucanases takes place respectively in log-phase and stationary-phase cells. The results show that there are marked differences in the elution profiles on Sephadex G-50 of fractions containing beta-glucanase from cells grown for 12, 24, 48, 72, and 96 h. The possibility either of replacement changes in fractions containing beta-glucanase activity or of a different synthesis of each beta-glucanase during the growth of the yeast is discussed. The results suggest that all fractions containing beta-glucanases hydrolyze both beta-(1 leads to 3) and beta-(1 leads to 6) linkages. Evidence in support of the conclusion that a low molecular form of beta-glucanase has a molecular weight of 2100 +/- 100 is also shown.", "contents": "Beta-glucanases in the yeast Cryptococcus albidus var. aerius. Production and separation of beta-glucanases in asynchronous cultures. beta-Glucanases were detected in cell-free extracts of the yeast Cryptococcus albidus var. aerius when grown on glucose as the sole carbon source. The production of beta-glucanases was followed in log-phase cells and stationary-phase cells; the maximal production of beta-(1 leads to 3) and beta-(1 leads to 6) glucanases takes place respectively in log-phase and stationary-phase cells. The results show that there are marked differences in the elution profiles on Sephadex G-50 of fractions containing beta-glucanase from cells grown for 12, 24, 48, 72, and 96 h. The possibility either of replacement changes in fractions containing beta-glucanase activity or of a different synthesis of each beta-glucanase during the growth of the yeast is discussed. The results suggest that all fractions containing beta-glucanases hydrolyze both beta-(1 leads to 3) and beta-(1 leads to 6) linkages. Evidence in support of the conclusion that a low molecular form of beta-glucanase has a molecular weight of 2100 +/- 100 is also shown."}
{"id": "PMID:4214", "title": "Temperature-pH effect upon germination of bacterial spores.", "content": "Using several kinds of criteria for the germination of bacterial spores, germination-pH curves were drawn for Bacillus subtilis spores observed at different temperatures. The experiments revealed that optimum pH for spore germination was markedly changed by changing the incubation temperature; the optimum pH for germination was 7.4 at 37 degrees C and 5.4 at 10 degrees C. A possible mechanism involved in this phenomenon is discussed.", "contents": "Temperature-pH effect upon germination of bacterial spores. Using several kinds of criteria for the germination of bacterial spores, germination-pH curves were drawn for Bacillus subtilis spores observed at different temperatures. The experiments revealed that optimum pH for spore germination was markedly changed by changing the incubation temperature; the optimum pH for germination was 7.4 at 37 degrees C and 5.4 at 10 degrees C. A possible mechanism involved in this phenomenon is discussed."}
{"id": "PMID:4215", "title": "Effect of variou cultural conditions on the fatty acid and lipid composition of Choanephora cucurbitarum.", "content": "The fatty acid composition of the total and polar lipid fractions of Choanephora cucurbitarum grown under different cultural conditions were analyzed by thin-layer and gas-liquid chromatography. It was observed that temperature, age, pH, and light influenced the degree of unsaturation, this being due mainly to changes in the gamma-linolenic acid concentration. The conditions used in this study did not alter the qualitative profile of fatty acids normally present in the organism. Neither did these conditions stimulate the production of further long-chain fatty acids (C20-C26) beyond gamma-linolenic acid (C18:3) as reported earlier using growth media containing glutamic acid. The fatty acid pattern of lipid fractions though the same qualitatively, differed quantitatively. The polar lipid fractions, phosphatidyl choline, phosphatidyl ethanolamine, and diphosphatidyl glycerol showed an appreciable variation in gamma-linolenic acid content under different cultural conditions. The degree of unsaturation of the various lipid fractions decreased with increases in temperature, light intensity, and pH, but within each treatment the same pattern of decreasing degree of unsaturation with increasing age was observed. The significance of these observations is discussed.", "contents": "Effect of variou cultural conditions on the fatty acid and lipid composition of Choanephora cucurbitarum. The fatty acid composition of the total and polar lipid fractions of Choanephora cucurbitarum grown under different cultural conditions were analyzed by thin-layer and gas-liquid chromatography. It was observed that temperature, age, pH, and light influenced the degree of unsaturation, this being due mainly to changes in the gamma-linolenic acid concentration. The conditions used in this study did not alter the qualitative profile of fatty acids normally present in the organism. Neither did these conditions stimulate the production of further long-chain fatty acids (C20-C26) beyond gamma-linolenic acid (C18:3) as reported earlier using growth media containing glutamic acid. The fatty acid pattern of lipid fractions though the same qualitatively, differed quantitatively. The polar lipid fractions, phosphatidyl choline, phosphatidyl ethanolamine, and diphosphatidyl glycerol showed an appreciable variation in gamma-linolenic acid content under different cultural conditions. The degree of unsaturation of the various lipid fractions decreased with increases in temperature, light intensity, and pH, but within each treatment the same pattern of decreasing degree of unsaturation with increasing age was observed. The significance of these observations is discussed."}
{"id": "PMID:4216", "title": "Superficial cell-wall layers on Spirillum \"Ordal\" and their in vitro reassembly.", "content": "The cell envelope of Sporillum sp. strain \"Ordal\" (possibly a variety of S. anulus) demonstrated multiple superficial wall layers which were diverse in their macromolecular arrays. Negative staining and freeze-etching techniques revealed an outer hexagonally packed layer and an inner tetragonally packed layer. However, both thin sections and freeze-etched cleavages of the wall showed that each of these regular structures rested upon a backing layer, and that there was a delicate amorphous layer overlying the outer hexagonal array. Rotary integration, optical deffraction, and reconstruction of image were used to clarify measurements of each array and to verify the validity of a diagrammatic model of the outer hexagonal system. The integrity of these layers required suitable cations (Ca2+ appeared essential) and pH (pH less than or equal to 4.6 dissociated most superficial layers). These observations aided in the development of a low-pH cationic-substitution technique, in which Na+ replaced essential Ca2+, for extraction of the layers from the cell surface. Dialysis to remove Na+ and restoration of Ca2+ initiated in vitro reassembly of the superficial layer components until regularly structured assembly products were formed.", "contents": "Superficial cell-wall layers on Spirillum \"Ordal\" and their in vitro reassembly. The cell envelope of Sporillum sp. strain \"Ordal\" (possibly a variety of S. anulus) demonstrated multiple superficial wall layers which were diverse in their macromolecular arrays. Negative staining and freeze-etching techniques revealed an outer hexagonally packed layer and an inner tetragonally packed layer. However, both thin sections and freeze-etched cleavages of the wall showed that each of these regular structures rested upon a backing layer, and that there was a delicate amorphous layer overlying the outer hexagonal array. Rotary integration, optical deffraction, and reconstruction of image were used to clarify measurements of each array and to verify the validity of a diagrammatic model of the outer hexagonal system. The integrity of these layers required suitable cations (Ca2+ appeared essential) and pH (pH less than or equal to 4.6 dissociated most superficial layers). These observations aided in the development of a low-pH cationic-substitution technique, in which Na+ replaced essential Ca2+, for extraction of the layers from the cell surface. Dialysis to remove Na+ and restoration of Ca2+ initiated in vitro reassembly of the superficial layer components until regularly structured assembly products were formed."}
{"id": "PMID:4217", "title": "Premature labour.", "content": "Prematurity is by far the commonest cause of neonatal morbidity and mortality. The management of premature labour is empirical because little is understood about the mechanism of labour. Effective uterine relaxant drugs have an important, albeit minor role. Phototherapy has reduced the complications of neonatal hyperbilirubinemia, and the beneficial effect of antepartum corticosteroid therapy in minimizing the risk of respiratory distress syndrome is now convincing. Prophylactic antibiotic therapy in premature rupture of the membranes does not alter perinatal mortality, although postpartum maternal morbidity is reduced. The introduction of neonatal intensive care units has improved the survival rate of premature infants. Sound clinical judgement remains the mainstay in the management of premature labour.", "contents": "Premature labour. Prematurity is by far the commonest cause of neonatal morbidity and mortality. The management of premature labour is empirical because little is understood about the mechanism of labour. Effective uterine relaxant drugs have an important, albeit minor role. Phototherapy has reduced the complications of neonatal hyperbilirubinemia, and the beneficial effect of antepartum corticosteroid therapy in minimizing the risk of respiratory distress syndrome is now convincing. Prophylactic antibiotic therapy in premature rupture of the membranes does not alter perinatal mortality, although postpartum maternal morbidity is reduced. The introduction of neonatal intensive care units has improved the survival rate of premature infants. Sound clinical judgement remains the mainstay in the management of premature labour."}
{"id": "PMID:4218", "title": "Liver metastases found by follow-up of patients operated on for colorectal cancer.", "content": "One hundred and twenty-six patients earlier operated on for colorectal cancer were followed-up once yearly with serum screening tests. The activities of alkaline phosphatase (AP) and gammaglutamyltranspeptidase (GT) were recorded. 58 patients had positive tests. The majority of the patients with liver metastases (20/21) was possible to encircle with these simple serum tests. 38 of the 58 \"screening positive patients\" were further investigated with celiac angiography and/or liver scintigraphy and liver metastases were very suspect in 29 of these patients. 18 of them were laparotomized and the suspicion was verified in 8.7 of these patients could be subjected to surgery against their liver tumours and 2 of them have then survived more than 2 years. The authors suggest a follow-up system with shorter interval between the examinations.", "contents": "Liver metastases found by follow-up of patients operated on for colorectal cancer. One hundred and twenty-six patients earlier operated on for colorectal cancer were followed-up once yearly with serum screening tests. The activities of alkaline phosphatase (AP) and gammaglutamyltranspeptidase (GT) were recorded. 58 patients had positive tests. The majority of the patients with liver metastases (20/21) was possible to encircle with these simple serum tests. 38 of the 58 \"screening positive patients\" were further investigated with celiac angiography and/or liver scintigraphy and liver metastases were very suspect in 29 of these patients. 18 of them were laparotomized and the suspicion was verified in 8.7 of these patients could be subjected to surgery against their liver tumours and 2 of them have then survived more than 2 years. The authors suggest a follow-up system with shorter interval between the examinations."}
{"id": "PMID:4219", "title": "Carcinoembryonic antigen and phosphohexose isomerase, gammaglutamyl transpeptidase and lactate dehydorgenase levels in patients with and without liver metastases.", "content": "Plasma carcinoembryonic antigen (CEA) and serum enzyme levels of phosphohexose isomerase (PHI), gamma-glutamyl transpeptidase (psi-GTP), and lactate dehydrogenase (LDH) were measured in 147 patients with malignancy. Levels were higher in patients (particularly with G.I., breast and lung cancers) than in normals or in patients with cancer in clinical remission. Elevations of CEA and of all three enzymes in blood were most frequent in patients with hepatic metastases. CEA elevations correlated directly with PHI levels. Seventy-eight percent of patients with metastatic G.I. cancer could be identified by CEA (greater than 5 ng/ml) alone, as well as 38% with breast cancer and 85% with lung cancer; but only 17% of other cancers could be identified by CEA alone. CEA or one or more enzymes was elevated in 64% of metastatic breast cancer patients, 92% of lung cancer and 41% of other cancers, but enzyme measurement did not increase identification of G.I. cancer over that achieved by CEA alone. These findings suggest that circulating levels of CEA, PHI, psi-GTP and LDH may reflect a direct contribution from the malignant tissue and/or liver malfunction secondary to liver replacement.", "contents": "Carcinoembryonic antigen and phosphohexose isomerase, gammaglutamyl transpeptidase and lactate dehydorgenase levels in patients with and without liver metastases. Plasma carcinoembryonic antigen (CEA) and serum enzyme levels of phosphohexose isomerase (PHI), gamma-glutamyl transpeptidase (psi-GTP), and lactate dehydrogenase (LDH) were measured in 147 patients with malignancy. Levels were higher in patients (particularly with G.I., breast and lung cancers) than in normals or in patients with cancer in clinical remission. Elevations of CEA and of all three enzymes in blood were most frequent in patients with hepatic metastases. CEA elevations correlated directly with PHI levels. Seventy-eight percent of patients with metastatic G.I. cancer could be identified by CEA (greater than 5 ng/ml) alone, as well as 38% with breast cancer and 85% with lung cancer; but only 17% of other cancers could be identified by CEA alone. CEA or one or more enzymes was elevated in 64% of metastatic breast cancer patients, 92% of lung cancer and 41% of other cancers, but enzyme measurement did not increase identification of G.I. cancer over that achieved by CEA alone. These findings suggest that circulating levels of CEA, PHI, psi-GTP and LDH may reflect a direct contribution from the malignant tissue and/or liver malfunction secondary to liver replacement."}
{"id": "PMID:4220", "title": "Controlled environment culture of bone marrow explants from human myeloma.", "content": "Bone marrow biopsy specimens from patients with myeloma were cultured in either 1 of 2 thin-film culture systems, a controlled environment steady state system or a rocker tube configuration of the system, for periods up to 42 days. Both functional and morphological characteristics of the myeloma cells were well-maintained in these systems. Cytocentrifuge preparations of the culture media disclosed hematopoietic cells that included from 5% to almost 100% plasma cells. Histological examination of the cultured specimens disclosed infiltration of the marrow with myeloma cells. Myeloma proteins were released at a steady rate throughout the period of culture after the 1st 4 days. Bone-resorbing activity was demonstrated in the culture media in 7 of 9 myeloma culture media and was well maintained, particularly during the 1st week of culture. This activity was associated with severe osteolytic lesions in the donor patient and marked infiltration of the cultured specimen by myeloma cells. The potential use of these organ culture systems for the further definitive identification of the factor responsible for bone destruction in myeloma is discussed.", "contents": "Controlled environment culture of bone marrow explants from human myeloma. Bone marrow biopsy specimens from patients with myeloma were cultured in either 1 of 2 thin-film culture systems, a controlled environment steady state system or a rocker tube configuration of the system, for periods up to 42 days. Both functional and morphological characteristics of the myeloma cells were well-maintained in these systems. Cytocentrifuge preparations of the culture media disclosed hematopoietic cells that included from 5% to almost 100% plasma cells. Histological examination of the cultured specimens disclosed infiltration of the marrow with myeloma cells. Myeloma proteins were released at a steady rate throughout the period of culture after the 1st 4 days. Bone-resorbing activity was demonstrated in the culture media in 7 of 9 myeloma culture media and was well maintained, particularly during the 1st week of culture. This activity was associated with severe osteolytic lesions in the donor patient and marked infiltration of the cultured specimen by myeloma cells. The potential use of these organ culture systems for the further definitive identification of the factor responsible for bone destruction in myeloma is discussed."}
{"id": "PMID:4221", "title": "Binding of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea to L1210 cell nuclear proteins.", "content": "The binding of 1-(2-chloroethyl)-3-(cyclohexyl)-1-nitrosourea (CCNU) to the proteins of the L1210 cell nucleus has been studied using both [cyclohexyl-14C]CCNU and [chloroethyl-14C]CCNU. Most of the bound [cyclohexyl-14C] moiety of CCNU was found to exist in a form that was stable in acid solution but labile and dialyzable in alkaline solution. A small amount of the cyclohexyl moiety was bound to histones in a stable, nondialyzable form. The drug/protein ratio for the H1 histone was about 0.01 to 0.02 mole/mole. No binding of the cyclohexyl group to acidic proteins or of the chloroethyl group to either histones or acidic proteins was observed. Thus, the interaction of CCNU with the proteins of the cell nucleus can be defined in terms of the modification of histones by the cyclohexyl moiety.", "contents": "Binding of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea to L1210 cell nuclear proteins. The binding of 1-(2-chloroethyl)-3-(cyclohexyl)-1-nitrosourea (CCNU) to the proteins of the L1210 cell nucleus has been studied using both [cyclohexyl-14C]CCNU and [chloroethyl-14C]CCNU. Most of the bound [cyclohexyl-14C] moiety of CCNU was found to exist in a form that was stable in acid solution but labile and dialyzable in alkaline solution. A small amount of the cyclohexyl moiety was bound to histones in a stable, nondialyzable form. The drug/protein ratio for the H1 histone was about 0.01 to 0.02 mole/mole. No binding of the cyclohexyl group to acidic proteins or of the chloroethyl group to either histones or acidic proteins was observed. Thus, the interaction of CCNU with the proteins of the cell nucleus can be defined in terms of the modification of histones by the cyclohexyl moiety."}
{"id": "PMID:4222", "title": "31P nuclear magnetic resonance-pH titrations of myo-inositol hexaphosphate.", "content": "With the use of 31P n.m.r. spectroscopy, the separate pKa values of each of the six phosphoric monoester groups of myo-inositol hexaphosphate were determined. The range of hydrogen-ion concentrations covered extended from that required for the phosphonium salts to that for the full dodecyl anion, and the determinations were carried out in the presence of sodium and tetrabutylammonium cations. The pKa for each phosphate grouping in the transition from the free acid forms of each group to the monoanion form of each group was determined to be: 1.1, C-2; 1.5, C-1 and C-3; 2.1, C-4 and C-6; and 1.7, C-5. In the mono- to di-anion transition, the pKa values were: 6.85, C-2; 7.60, C-5; 5.70 and 12.0, C-1 and C-3; and 10.0, C-4 and C-6. These data and the appearance of the 31P hexaphosphate n.m.r. multiplet are discussed in terms of conformations of myo-inositol hexaphosphate.", "contents": "31P nuclear magnetic resonance-pH titrations of myo-inositol hexaphosphate. With the use of 31P n.m.r. spectroscopy, the separate pKa values of each of the six phosphoric monoester groups of myo-inositol hexaphosphate were determined. The range of hydrogen-ion concentrations covered extended from that required for the phosphonium salts to that for the full dodecyl anion, and the determinations were carried out in the presence of sodium and tetrabutylammonium cations. The pKa for each phosphate grouping in the transition from the free acid forms of each group to the monoanion form of each group was determined to be: 1.1, C-2; 1.5, C-1 and C-3; 2.1, C-4 and C-6; and 1.7, C-5. In the mono- to di-anion transition, the pKa values were: 6.85, C-2; 7.60, C-5; 5.70 and 12.0, C-1 and C-3; and 10.0, C-4 and C-6. These data and the appearance of the 31P hexaphosphate n.m.r. multiplet are discussed in terms of conformations of myo-inositol hexaphosphate."}
{"id": "PMID:4224", "title": "Age dependence of the number of the stem cells in haemopoietic tissues of rats.", "content": "The number and concentration of haemopoietic stem cells in the femoral bone marrow and spleen of Wistar rats of different ages were investigated. Stem cells were assayed by the spleen colony technique in irradiated rat recipients. The ability of the recipient spleen to harvest transplanted tissue as a macroscopic colony was found to be dependent on the recipient's age. Changes with senescence were observed also in the concentration and the size of the stem cell compartment both in the marrow and spleen. No differences were demonstrated in the seeding of transplanted colony-forming units into the spleen of recipients of 1 and 4 months of age. A rats-mice strain difference in the effect of senescence on the haemopoietic stem cells is discussed.", "contents": "Age dependence of the number of the stem cells in haemopoietic tissues of rats. The number and concentration of haemopoietic stem cells in the femoral bone marrow and spleen of Wistar rats of different ages were investigated. Stem cells were assayed by the spleen colony technique in irradiated rat recipients. The ability of the recipient spleen to harvest transplanted tissue as a macroscopic colony was found to be dependent on the recipient's age. Changes with senescence were observed also in the concentration and the size of the stem cell compartment both in the marrow and spleen. No differences were demonstrated in the seeding of transplanted colony-forming units into the spleen of recipients of 1 and 4 months of age. A rats-mice strain difference in the effect of senescence on the haemopoietic stem cells is discussed."}
{"id": "PMID:4225", "title": "Kinetics of haemopoietic recovery in endotoxin-treated mice.", "content": "Kinetics of mouse spleen colony forming units were studied after intra-peritoneal injection of 1 mug/blody weight bacterial endotoxin S. typhosa. When these mice were used as unirradiated and sublethally irradiated donors, it was possible to study the effect of the endotoxin injection upon the cells. Use of the treated mice as irradiated recipients of normal cells gave information about the host effect. In treated unirradiated mice, the total nucleated cell and the CFU counts were disturbed, and 2 days later a large fraction of the CFU were found in the DNA synthesis (S) phase. This meant that injection of endotoxin generated factors affecting the kinetics of the CFU and triggering the resting CFU into the proliferative cycle. If then the mice were given supralethal irradiation and used as recipients of normal bone marrow cells, more CFU seeded to the spleen as compared to normal recipients; but the dip and the growth rate of the CFU were not changed. Hence the endotoxin-generated factors had been eliminated in 2 days. A total body sublethal irradiation by 400 rad X-ray 2 days after endotoxin injection reduced the post-irradiation dip in the recovery curve of the CFU, indicating that though the factors affecting the cell kinetics had been eliminated, the cycling CFU behaved like a growing population. During the first week, the growth rate of the CFU remained the same as in control irradiated mice. The growth rate of the spleen CFU of the endotoxin-treated mice slowed down during the second week, and their self-replicating ability was low. Fluctuations in the DNA synthesizing fraction of the spleen CFU suggested a variability in the ratio of the length of the S phase and the cell generation time.", "contents": "Kinetics of haemopoietic recovery in endotoxin-treated mice. Kinetics of mouse spleen colony forming units were studied after intra-peritoneal injection of 1 mug/blody weight bacterial endotoxin S. typhosa. When these mice were used as unirradiated and sublethally irradiated donors, it was possible to study the effect of the endotoxin injection upon the cells. Use of the treated mice as irradiated recipients of normal cells gave information about the host effect. In treated unirradiated mice, the total nucleated cell and the CFU counts were disturbed, and 2 days later a large fraction of the CFU were found in the DNA synthesis (S) phase. This meant that injection of endotoxin generated factors affecting the kinetics of the CFU and triggering the resting CFU into the proliferative cycle. If then the mice were given supralethal irradiation and used as recipients of normal bone marrow cells, more CFU seeded to the spleen as compared to normal recipients; but the dip and the growth rate of the CFU were not changed. Hence the endotoxin-generated factors had been eliminated in 2 days. A total body sublethal irradiation by 400 rad X-ray 2 days after endotoxin injection reduced the post-irradiation dip in the recovery curve of the CFU, indicating that though the factors affecting the cell kinetics had been eliminated, the cycling CFU behaved like a growing population. During the first week, the growth rate of the CFU remained the same as in control irradiated mice. The growth rate of the spleen CFU of the endotoxin-treated mice slowed down during the second week, and their self-replicating ability was low. Fluctuations in the DNA synthesizing fraction of the spleen CFU suggested a variability in the ratio of the length of the S phase and the cell generation time."}
{"id": "PMID:4231", "title": "[New interpretation of the symmetry of Cereus pedunculatus (Actiniaria) during embryonic development].", "content": "A spatial reconstitution is used to determine with precision the relative position of pharynx and mesenteries during the embryonic development of Cereus pedunculatus. Three successive stages are described for embryonic symmetrisation.", "contents": "[New interpretation of the symmetry of Cereus pedunculatus (Actiniaria) during embryonic development]. A spatial reconstitution is used to determine with precision the relative position of pharynx and mesenteries during the embryonic development of Cereus pedunculatus. Three successive stages are described for embryonic symmetrisation."}
{"id": "PMID:4232", "title": "[Effect of ligating the pancreatic duct on the intestinal pH in rabbits].", "content": "In rabbits whose pancreatic ducts were ligatured, significant pH changes were observed in the anterior parts of the digestive tract (antrum and duodenum) but not in the posterior parts (jejunum and ileum) as could have been expected. These changes do not seem to be directly related to the lack of pancreatic juice, which leads one to think that, in the rabbit this secretion only plays a very limited role in the neutralisation processes.", "contents": "[Effect of ligating the pancreatic duct on the intestinal pH in rabbits]. In rabbits whose pancreatic ducts were ligatured, significant pH changes were observed in the anterior parts of the digestive tract (antrum and duodenum) but not in the posterior parts (jejunum and ileum) as could have been expected. These changes do not seem to be directly related to the lack of pancreatic juice, which leads one to think that, in the rabbit this secretion only plays a very limited role in the neutralisation processes."}
{"id": "PMID:4233", "title": "[Demonstration of acidophilic neurosecretory cells in Crepidula fornicata Phil. (Mollusca, Gasteropoda, Prosobranchia) using the fluorescent dye, Geranine G].", "content": "The Fluorochrome Geranine G binds to acidophilic neurosecretory cells and produces red orange fluorescence. Chromolipids and pigments show green fluorescence. This method is easy and sensitive. Fluorescence fading during irradiation is low.", "contents": "[Demonstration of acidophilic neurosecretory cells in Crepidula fornicata Phil. (Mollusca, Gasteropoda, Prosobranchia) using the fluorescent dye, Geranine G]. The Fluorochrome Geranine G binds to acidophilic neurosecretory cells and produces red orange fluorescence. Chromolipids and pigments show green fluorescence. This method is easy and sensitive. Fluorescence fading during irradiation is low."}
{"id": "PMID:4234", "title": "[A glycoprotein: galactosyltransferase activity in the ascitic fluid and serum of mice with the YC8 tumor].", "content": "Tranfer of (14C)-gal from exogenous UDP(14C)-gal has been demonstrated with ovomucoid as glycoprotein acceptor in ascitic fluid sera from Balb/c mice bearing isogenic YC8 tumor. Transfer exists without ovomucoid, in great ratio in ascitic fluid and in sera from ascitic mice too, showing occurrence of endogenous acceptors, the origin of which has to be proved.", "contents": "[A glycoprotein: galactosyltransferase activity in the ascitic fluid and serum of mice with the YC8 tumor]. Tranfer of (14C)-gal from exogenous UDP(14C)-gal has been demonstrated with ovomucoid as glycoprotein acceptor in ascitic fluid sera from Balb/c mice bearing isogenic YC8 tumor. Transfer exists without ovomucoid, in great ratio in ascitic fluid and in sera from ascitic mice too, showing occurrence of endogenous acceptors, the origin of which has to be proved."}
{"id": "PMID:4235", "title": "Activity of gamma-glutamyl transpeptidase in serum of patients receiving anticonvulsant of anticoagulant therapy.", "content": "1. Effects of chronic anticoagulant therapy in heart patients and anticonvulsant therapy in epileptics on gamma-glutamyl transpeptidase activity in serum were investigated. 2. The enzyme was elevated in 22% of 18 patients receiving anticoagulants. In these patients prothrombin time was also abnormally high. 3. 84% of 65 epileptics exhibited elevated gamma-glutamyl transpeptidase activity, 67% of which were not associated with elevated alkaline phosphatase or aspartate aminotransferase activities. In these latter cases, involvement of the liver was not apparent. 4. Possible relationships of anticonvulsant mediated enzyme induction or hepatic toxicity to elevated gamma-glutamyl transpeptidase activity in serum in epileptics is discussed.", "contents": "Activity of gamma-glutamyl transpeptidase in serum of patients receiving anticonvulsant of anticoagulant therapy. 1. Effects of chronic anticoagulant therapy in heart patients and anticonvulsant therapy in epileptics on gamma-glutamyl transpeptidase activity in serum were investigated. 2. The enzyme was elevated in 22% of 18 patients receiving anticoagulants. In these patients prothrombin time was also abnormally high. 3. 84% of 65 epileptics exhibited elevated gamma-glutamyl transpeptidase activity, 67% of which were not associated with elevated alkaline phosphatase or aspartate aminotransferase activities. In these latter cases, involvement of the liver was not apparent. 4. Possible relationships of anticonvulsant mediated enzyme induction or hepatic toxicity to elevated gamma-glutamyl transpeptidase activity in serum in epileptics is discussed."}
{"id": "PMID:4236", "title": "Human saliva peroxidase: microanalytical isoelectric fractionation and properties in normal persons and in cases with neuronal ceroid-lipofuscinosis.", "content": "Human saliva contains a high peroxidase activity that can be estimated spectrophotometrically with the hydrogen donor p-phenylenediamine and the substrate hydrogen peroxide from 20 mul of material. The pH optimum of the enzyme with citrate-phosphate buffer is 5.5. After microanalytical isoelectric fractionation 3 main isoenzyme components at pI 8.6, 6.5 and 4.3, and a number of isoenzyme subfractions at pI 9.5, 7.3 and 3.8 are detectable. In 3 patients with the juvenile form of neuronal ceroid-lipofuscinosis (type Spielmeyer-Vogt), in which a deficiency of leukocyte peroxidase had been reported by other authors, both the total activity of saliva peroxidase and the activity of individual isoenzymes were found to be within normal limits. These findings are not consistent with a generalized peroxidase deficiency in this disease.", "contents": "Human saliva peroxidase: microanalytical isoelectric fractionation and properties in normal persons and in cases with neuronal ceroid-lipofuscinosis. Human saliva contains a high peroxidase activity that can be estimated spectrophotometrically with the hydrogen donor p-phenylenediamine and the substrate hydrogen peroxide from 20 mul of material. The pH optimum of the enzyme with citrate-phosphate buffer is 5.5. After microanalytical isoelectric fractionation 3 main isoenzyme components at pI 8.6, 6.5 and 4.3, and a number of isoenzyme subfractions at pI 9.5, 7.3 and 3.8 are detectable. In 3 patients with the juvenile form of neuronal ceroid-lipofuscinosis (type Spielmeyer-Vogt), in which a deficiency of leukocyte peroxidase had been reported by other authors, both the total activity of saliva peroxidase and the activity of individual isoenzymes were found to be within normal limits. These findings are not consistent with a generalized peroxidase deficiency in this disease."}
{"id": "PMID:4237", "title": "Theoretical approaches to estimation of plasma renin activity: a review and some original observations.", "content": "Performance of accurrate, reproducible, and interpretable assays for plasma renin activity and other components of the renin/angiotensin system in the clinical setting requires a clear understanding of the various reactions in the renin/angiotensin cascade and the nature of their interactions. Plasma renin activity, the rate of angiotensin generations from plasma incubated in vitro, is the most commonly used clinical index of function in the renin/angiotensin system. Renin activity is measured by radioimmunoassay of angiotensin I generated in vitro under carefully controlled conditions. The value obtained for plasma renin activity depends on pH and duration of incubation and on the method used to protect the angiotensin I generated. We recommend incubation at neutral pH in buffered plasma for three hours in the presence of either ethylenediaminetetraacetate + 8-hydroxyquinolone + dimercaprol or ethylenediaminetetraacetate + phenylmethylsulfonylfluoride. Addition of a standard preparation of human renin to the plasma incubation step of the renin activity assay serves the dual purpose of permitting measurement of renin activity and furnishing an internal standard for comparison of assay procedures. The many variables among renin assay methods can be cancelled by referring to a common internal renin standard.", "contents": "Theoretical approaches to estimation of plasma renin activity: a review and some original observations. Performance of accurrate, reproducible, and interpretable assays for plasma renin activity and other components of the renin/angiotensin system in the clinical setting requires a clear understanding of the various reactions in the renin/angiotensin cascade and the nature of their interactions. Plasma renin activity, the rate of angiotensin generations from plasma incubated in vitro, is the most commonly used clinical index of function in the renin/angiotensin system. Renin activity is measured by radioimmunoassay of angiotensin I generated in vitro under carefully controlled conditions. The value obtained for plasma renin activity depends on pH and duration of incubation and on the method used to protect the angiotensin I generated. We recommend incubation at neutral pH in buffered plasma for three hours in the presence of either ethylenediaminetetraacetate + 8-hydroxyquinolone + dimercaprol or ethylenediaminetetraacetate + phenylmethylsulfonylfluoride. Addition of a standard preparation of human renin to the plasma incubation step of the renin activity assay serves the dual purpose of permitting measurement of renin activity and furnishing an internal standard for comparison of assay procedures. The many variables among renin assay methods can be cancelled by referring to a common internal renin standard."}
{"id": "PMID:4238", "title": "Improved specificity of serum albumin determination and estimation of \"acute phase reactants\" by use of the bromcresol green reaction.", "content": "The reaction of serum samples with bromcresol green proceeds in two steps. Albumin is responsible for the faster (less than 1 min) reaction; the slower (30-min) reaction is a measure of \"acute phase reactant(s)\" in serum. Serum is simply mixed with bromcresol green reagent and the absorbance is measured twice, immediately and at 60 min. Albumin concentrations, determined from the absorbance at 0 min, correlate well with those determined by Laurell \"rocket\" immunoelectrophoresis; r = 0.95 with no certain deviation from unity for the slope and with a negligible difference at zero concentration. The slow reaction was expressed as deltaA% = 100 (deltaAs/deltaAv) where deltaAs and delta Av are the changes in absorbance between 60 and 0 min for the sample and a commercial control serum, respectively. The value for deltaA% correlates well with the percentage of alpha2-fraction as determined by electrophoresis on cellulose acetate, as well as with orosomucoid and ceruloplasmin, all of which are acute phase reactant(s). Whether these proteins or other acute phase reactant(s) actually cause the slow reaction has not yet been established.", "contents": "Improved specificity of serum albumin determination and estimation of \"acute phase reactants\" by use of the bromcresol green reaction. The reaction of serum samples with bromcresol green proceeds in two steps. Albumin is responsible for the faster (less than 1 min) reaction; the slower (30-min) reaction is a measure of \"acute phase reactant(s)\" in serum. Serum is simply mixed with bromcresol green reagent and the absorbance is measured twice, immediately and at 60 min. Albumin concentrations, determined from the absorbance at 0 min, correlate well with those determined by Laurell \"rocket\" immunoelectrophoresis; r = 0.95 with no certain deviation from unity for the slope and with a negligible difference at zero concentration. The slow reaction was expressed as deltaA% = 100 (deltaAs/deltaAv) where deltaAs and delta Av are the changes in absorbance between 60 and 0 min for the sample and a commercial control serum, respectively. The value for deltaA% correlates well with the percentage of alpha2-fraction as determined by electrophoresis on cellulose acetate, as well as with orosomucoid and ceruloplasmin, all of which are acute phase reactant(s). Whether these proteins or other acute phase reactant(s) actually cause the slow reaction has not yet been established."}
{"id": "PMID:4239", "title": "Evaluation of lipase activity in serum by radial enzyme diffusion.", "content": "Results of determination of serum lipase by radial enzyme diffusion correlate well with those by a titrimetric reference method in the abnormal range. The specificity of the diffusion assay allows the differentiation of patients with pancreatic disease, even when the lipase activity of the serum is within the normal limits of the tritrimetric assay. Pancreatic lipase is not detectable by the diffusion assay in the serum of individuals who are free from pancreatic disease.", "contents": "Evaluation of lipase activity in serum by radial enzyme diffusion. Results of determination of serum lipase by radial enzyme diffusion correlate well with those by a titrimetric reference method in the abnormal range. The specificity of the diffusion assay allows the differentiation of patients with pancreatic disease, even when the lipase activity of the serum is within the normal limits of the tritrimetric assay. Pancreatic lipase is not detectable by the diffusion assay in the serum of individuals who are free from pancreatic disease."}
{"id": "PMID:4240", "title": "Creatine kinase in serum: 1. Determination of optimum reaction conditions.", "content": "To establish optimum conditions for creatine kinase (EC 2.7.3.2) activity measurement with the creatine phosphate in equilibrium creatine reaction, we re-examined all kinetics factors relevant to an optimal and standardized enzyme assay at 30 and 25 degrees C. We determined the pH optimum in vaious buffers, considering the effect of the type and concentration of the buffer, as well as the influence of various buffer anions on the activity. The relation between activity and substrate concentration was shown and the apparent Michaelis constants of creatine kinase for creatine phosphate and ADP were evaluated. We tested the effect on creatine kinase measurement of the concentration of substrates (glucose and NADP+) in the auxillary and indicator reactions, especially the influence of the added auxiliary (hexokinase) and indicator (glucose-6-phosphate dehydrogenase) enzymes on the lag phase, at different temperatures. The NADP+ concentration proved to be the factor limiting the duration of constant reaction rate. We studied the inhibition of creatine kinase and adenylate kinase by AMP and established a convenient AMP concentration. For reactivation of creatine kinase, N-acetyl cysteine as sulfhydryl compound was introduced. Finally, we examined the relationship between activity and temperature.", "contents": "Creatine kinase in serum: 1. Determination of optimum reaction conditions. To establish optimum conditions for creatine kinase (EC 2.7.3.2) activity measurement with the creatine phosphate in equilibrium creatine reaction, we re-examined all kinetics factors relevant to an optimal and standardized enzyme assay at 30 and 25 degrees C. We determined the pH optimum in vaious buffers, considering the effect of the type and concentration of the buffer, as well as the influence of various buffer anions on the activity. The relation between activity and substrate concentration was shown and the apparent Michaelis constants of creatine kinase for creatine phosphate and ADP were evaluated. We tested the effect on creatine kinase measurement of the concentration of substrates (glucose and NADP+) in the auxillary and indicator reactions, especially the influence of the added auxiliary (hexokinase) and indicator (glucose-6-phosphate dehydrogenase) enzymes on the lag phase, at different temperatures. The NADP+ concentration proved to be the factor limiting the duration of constant reaction rate. We studied the inhibition of creatine kinase and adenylate kinase by AMP and established a convenient AMP concentration. For reactivation of creatine kinase, N-acetyl cysteine as sulfhydryl compound was introduced. Finally, we examined the relationship between activity and temperature."}
{"id": "PMID:4242", "title": "Radioiodination of human low density lipoprotein: a comparison of four methods.", "content": "A comparison has been made of four labelling techniques used to radioiodinate human low density lipoprotein (LDL). (1) Chloramine T iodination at pH 7.4 was 20-25% efficient and gave a product immunologically indistinguishable from native LDL. Approximately 30% of the incorporated radioactivity, however, was found in LDL lipids, and the metabolic decay of the labelled complex in rats did not obey first order kinetics. Radiolabelling at pH 10 reduced the uptake of 125I into lipids to 10% but also cut the overall incorporation of radioiodine by a factor of 7. (2) Lactoperoxidase labelling and (3) conjugation with iodinated N-succinimidyl-3-(4-hydroxyphenyl)propionate were highly efficient (100%), but incorporation of radioactivity into the lipid moiety was unacceptably high (approximately 30%). (4) The efficiency of iodine monochloride labelling was highly reproducible and the product was immunologically indistinguishable from native LDL. Incorporation of radioactivity into the lipid moiety was less than 4% when the I/protein ratio of the product was kept at or below 1 : 1. Decay of the radiolabelled LDL in rats was monoexponential.", "contents": "Radioiodination of human low density lipoprotein: a comparison of four methods. A comparison has been made of four labelling techniques used to radioiodinate human low density lipoprotein (LDL). (1) Chloramine T iodination at pH 7.4 was 20-25% efficient and gave a product immunologically indistinguishable from native LDL. Approximately 30% of the incorporated radioactivity, however, was found in LDL lipids, and the metabolic decay of the labelled complex in rats did not obey first order kinetics. Radiolabelling at pH 10 reduced the uptake of 125I into lipids to 10% but also cut the overall incorporation of radioiodine by a factor of 7. (2) Lactoperoxidase labelling and (3) conjugation with iodinated N-succinimidyl-3-(4-hydroxyphenyl)propionate were highly efficient (100%), but incorporation of radioactivity into the lipid moiety was unacceptably high (approximately 30%). (4) The efficiency of iodine monochloride labelling was highly reproducible and the product was immunologically indistinguishable from native LDL. Incorporation of radioactivity into the lipid moiety was less than 4% when the I/protein ratio of the product was kept at or below 1 : 1. Decay of the radiolabelled LDL in rats was monoexponential."}
{"id": "PMID:4243", "title": "Purification and properties of human acid-thermostable ribonucleases, and diagnosis of childhood pancreatic fibrosis.", "content": "Acid-thermostable ribonucleases were isolated from human pancreas, duodenal contents, liver, spleen, serum and urine, and purified 15--1000-fold. The pH optima, ionic requirements, and some of the specificity requirements, of these enzymes were investigated. The isolated enzymes formed two distinct groups: (a) The ribonucleases of the pancreas, duodenal contents and fraction A of serum and urine exhibit a pH optimum of 8.5, are inhibited by An2+ and Cu2+, and relatively rapidly hydrolyze the synthetic substrate uridine 3'-(alpha-naphthylphosphate); (b) the ribonucleases of the liver and spleen, and of fractions B of the serum and urine, with a pH optimum of 7, are less sensitive to An2+ and Cu2+, and exhibit negligible activity versus uridine 3'-(alpha-naphthylphosphate). Determination of the serum level of pancreatic-type ribonuclease activity, with the use of uridine 3'-(alpha-naphthylphosphate) or RNA as substrates, appears to be a valid diagnostic tool for pancreatic fibrosis in children.", "contents": "Purification and properties of human acid-thermostable ribonucleases, and diagnosis of childhood pancreatic fibrosis. Acid-thermostable ribonucleases were isolated from human pancreas, duodenal contents, liver, spleen, serum and urine, and purified 15--1000-fold. The pH optima, ionic requirements, and some of the specificity requirements, of these enzymes were investigated. The isolated enzymes formed two distinct groups: (a) The ribonucleases of the pancreas, duodenal contents and fraction A of serum and urine exhibit a pH optimum of 8.5, are inhibited by An2+ and Cu2+, and relatively rapidly hydrolyze the synthetic substrate uridine 3'-(alpha-naphthylphosphate); (b) the ribonucleases of the liver and spleen, and of fractions B of the serum and urine, with a pH optimum of 7, are less sensitive to An2+ and Cu2+, and exhibit negligible activity versus uridine 3'-(alpha-naphthylphosphate). Determination of the serum level of pancreatic-type ribonuclease activity, with the use of uridine 3'-(alpha-naphthylphosphate) or RNA as substrates, appears to be a valid diagnostic tool for pancreatic fibrosis in children."}
{"id": "PMID:4245", "title": "Physico-chemical and immunological properties of acid alpha-glucosidase from various human tissues in relation to glycogenosis type II (Pompe's disease).", "content": "The physico-chemical and immunological properties of acid alpha-glucosidase from various human tissues have been studied. Heat stability of acid alpha-glucosidase from heart, liver and skeletal muscle is identical, but for kidney some different results are obtained. Identical isoelectrofocussing patterns are found for heart, liver and skeletal muscle. Furthermore, the effect of antiserum against human liver acid alpha-glucosidase on the activity of acid alpha-glucosidase from various tissues is studied. The results are discussed in relation to glycogenosis type II (Pompe's disease).", "contents": "Physico-chemical and immunological properties of acid alpha-glucosidase from various human tissues in relation to glycogenosis type II (Pompe's disease). The physico-chemical and immunological properties of acid alpha-glucosidase from various human tissues have been studied. Heat stability of acid alpha-glucosidase from heart, liver and skeletal muscle is identical, but for kidney some different results are obtained. Identical isoelectrofocussing patterns are found for heart, liver and skeletal muscle. Furthermore, the effect of antiserum against human liver acid alpha-glucosidase on the activity of acid alpha-glucosidase from various tissues is studied. The results are discussed in relation to glycogenosis type II (Pompe's disease)."}
{"id": "PMID:4246", "title": "Partial purification and properties of ovine liver Echinococcus granulosus protoscolices phospholgucose isomerase.", "content": "Echinococcus granulosus protoscolex is the actual larval stage of the cestode causing echinococcosis both in man and animals. In the present report, certain properties of phosphoglucose isomerase from the ovine liver E. granulosus protoscolices have been studied and compared with those of the hydatid cyst fluid and the healthy ovine liver enzymes. The protoscolices enzyme prepared in a manner similar to the hydatid cyst fluid and the ovine liver enzymes exhibited the following properties: (1) pH optimum of 8.2 (2) KM value of 0.23 mM, (3) the enzyme was inhibited in the presence of high concentrations of alpha-D-glucose 6-phosphate, (4) no detectable inhibition of the enzyme was observed in the presence of phosphate ion up to 4.1 mM, (5) the protoscolices enzyme was less thermostable as compared to the hydatid cyst fluid and the ovine liver enzymes, (6) the protoscolices enzyme had a lower Ki value (0.7 mM) as compared to either the hydatid cyst fluid (1.1 mM) or the ovine liver enzymes (4.6 mM) when 6-phosphogluconic acid was used as a competitive inhibitor.", "contents": "Partial purification and properties of ovine liver Echinococcus granulosus protoscolices phospholgucose isomerase. Echinococcus granulosus protoscolex is the actual larval stage of the cestode causing echinococcosis both in man and animals. In the present report, certain properties of phosphoglucose isomerase from the ovine liver E. granulosus protoscolices have been studied and compared with those of the hydatid cyst fluid and the healthy ovine liver enzymes. The protoscolices enzyme prepared in a manner similar to the hydatid cyst fluid and the ovine liver enzymes exhibited the following properties: (1) pH optimum of 8.2 (2) KM value of 0.23 mM, (3) the enzyme was inhibited in the presence of high concentrations of alpha-D-glucose 6-phosphate, (4) no detectable inhibition of the enzyme was observed in the presence of phosphate ion up to 4.1 mM, (5) the protoscolices enzyme was less thermostable as compared to the hydatid cyst fluid and the ovine liver enzymes, (6) the protoscolices enzyme had a lower Ki value (0.7 mM) as compared to either the hydatid cyst fluid (1.1 mM) or the ovine liver enzymes (4.6 mM) when 6-phosphogluconic acid was used as a competitive inhibitor."}
{"id": "PMID:4247", "title": "Biochemical differences between the MB and MM isoenzymes of creatine kinase.", "content": "The biochemical properties of partially purified preparations of human myocardial MB and MM iosenzymes of creatine kinase have been compared with one another. Differences in substrate affinity, behaviour with inhibitors, and heat denaturation have been demonstrated. It is doubtful if the differences we have shown are sufficiently great to form the basis of a practical routine procedure for measuring serum levels of the MB isoenzyme.", "contents": "Biochemical differences between the MB and MM isoenzymes of creatine kinase. The biochemical properties of partially purified preparations of human myocardial MB and MM iosenzymes of creatine kinase have been compared with one another. Differences in substrate affinity, behaviour with inhibitors, and heat denaturation have been demonstrated. It is doubtful if the differences we have shown are sufficiently great to form the basis of a practical routine procedure for measuring serum levels of the MB isoenzyme."}
{"id": "PMID:4248", "title": "The estimation of phospholipids in bile.", "content": "Total and lipid phosphorus were measured in the duodenal aspirate of 24 fasting subjects following an injection of cholecystokinin. The lipid phosphorus values were lower than the total phosphorus, a difference most pronounced in dilute samples. Storage at -20 degrees C over 4 weeks resulted in a loss of over 50% lipid phosphorus. Such alterations in the lipid phosphorus affected the calculation of biliary phospholipid and hence the saturation index of cholesterol in bile causing it to be erroneously elevated. It is concluded that analysis of bile samples should be undertaken on freshly obtained samples and include a preliminary step for the extraction of lipids.", "contents": "The estimation of phospholipids in bile. Total and lipid phosphorus were measured in the duodenal aspirate of 24 fasting subjects following an injection of cholecystokinin. The lipid phosphorus values were lower than the total phosphorus, a difference most pronounced in dilute samples. Storage at -20 degrees C over 4 weeks resulted in a loss of over 50% lipid phosphorus. Such alterations in the lipid phosphorus affected the calculation of biliary phospholipid and hence the saturation index of cholesterol in bile causing it to be erroneously elevated. It is concluded that analysis of bile samples should be undertaken on freshly obtained samples and include a preliminary step for the extraction of lipids."}
{"id": "PMID:4249", "title": "Two alpha-glucosidases in cultured amniotic fluid cells and their differentiation in the prenatal diagnosis of Pompe's disease.", "content": "A sensitive fluorometric assay utilizing 4-methylumbelliferyl-alpha-D-glucopyranoside has been developed for the determination of alpha-glucosidase. The enhanced sensitivity was achieved by increasing the solubility of the substrate with a water miscible organic solvent. With this system, cultured amniotic fluid cells were found to have two major forms of alpha-glucosidase with somewhat overlapping acidic pH optima; one with pH optimum at 4.5 is deficient in Pompe's disease (type II glycogenosis), while one with pH optimum at 6.0 is not affected in this disease. Specificity for the pH 4 form of alpha-glucosidase was achieved by exploiting the greater thermal lability of the pH 6 enzyme. The pH 6 form of the enzyme was also detectable in freshly prepared extracts of cultured fibroblasts. The procedure is direct and simple and has been applied to the prenatal diagnosis in two pregnancies at risk for Pompe's disease.", "contents": "Two alpha-glucosidases in cultured amniotic fluid cells and their differentiation in the prenatal diagnosis of Pompe's disease. A sensitive fluorometric assay utilizing 4-methylumbelliferyl-alpha-D-glucopyranoside has been developed for the determination of alpha-glucosidase. The enhanced sensitivity was achieved by increasing the solubility of the substrate with a water miscible organic solvent. With this system, cultured amniotic fluid cells were found to have two major forms of alpha-glucosidase with somewhat overlapping acidic pH optima; one with pH optimum at 4.5 is deficient in Pompe's disease (type II glycogenosis), while one with pH optimum at 6.0 is not affected in this disease. Specificity for the pH 4 form of alpha-glucosidase was achieved by exploiting the greater thermal lability of the pH 6 enzyme. The pH 6 form of the enzyme was also detectable in freshly prepared extracts of cultured fibroblasts. The procedure is direct and simple and has been applied to the prenatal diagnosis in two pregnancies at risk for Pompe's disease."}
{"id": "PMID:4250", "title": "X-linked ichthyosis, bilateral cryptorchidism, hypogenitalism and mental retardation in two siblings.", "content": "Two brothers showed ichthyosis, bilateral cryptorchidism, hypogenitalism and mental retardation. In addition, the younger brother had short stature associated with disorders of secretions of insulin, ACTH and GH. This is the third reported case of the syndrome of ichthyosis and hypogonadism.", "contents": "X-linked ichthyosis, bilateral cryptorchidism, hypogenitalism and mental retardation in two siblings. Two brothers showed ichthyosis, bilateral cryptorchidism, hypogenitalism and mental retardation. In addition, the younger brother had short stature associated with disorders of secretions of insulin, ACTH and GH. This is the third reported case of the syndrome of ichthyosis and hypogonadism."}
{"id": "PMID:4251", "title": "A simple method for the cryopreservation of lymphocytes. Retention of specific immune effector functions by frozen-stored cells.", "content": "A simple, quick and inexpensive method for cryostorage of lymphocytes is discribed. When injected into appropriate normal recipients, frozen-stored rat and sheep lymphocytes caused GVH and NLT reactions respectively. Sheep lymphocytes remained viable after several months storage and functioned satisfactorily as 51Cr-labelled target cells in assays for cytotoxic antibodies. Lymphocytes, including immunoblasts, drained from sheep efferent lymphatics during immune responses to injected murine P815 cells or allogeneic lymphocytes survived freezing; when thawed the cells retained specific immune cytotoxic effector functions including the ability to secrete complement-dependent and leucocyte-dependent antibodies", "contents": "A simple method for the cryopreservation of lymphocytes. Retention of specific immune effector functions by frozen-stored cells. A simple, quick and inexpensive method for cryostorage of lymphocytes is discribed. When injected into appropriate normal recipients, frozen-stored rat and sheep lymphocytes caused GVH and NLT reactions respectively. Sheep lymphocytes remained viable after several months storage and functioned satisfactorily as 51Cr-labelled target cells in assays for cytotoxic antibodies. Lymphocytes, including immunoblasts, drained from sheep efferent lymphatics during immune responses to injected murine P815 cells or allogeneic lymphocytes survived freezing; when thawed the cells retained specific immune cytotoxic effector functions including the ability to secrete complement-dependent and leucocyte-dependent antibodies"}
{"id": "PMID:4252", "title": "Mechanism of post dialysis hyperventilation in  patients with chronic renal insufficiency.", "content": "Several hypotheses have been put forward to explain postdialysis hypocapnia. Three were tested in this study: impairment of tissue oxygenation by dialysis (D)-induced alkalosis (Bohr effect), the D disequilibrium syndrome, and the loss of carbon dioxide  (CO2) in D fluid. In 17 patients pre-DPCO2 was significantly correlated with plasma bicarbonate concentration (HCO3) and no disproportionate reduction of PCO2 was discernible. In 10 patients using a bath acetate concentration of 38 mEq/1 PCO2 was unchanged after D (35.4 versus 35.9 mm Hg before D), and was low relative to HCO3 whic increased from 21.2 to 28.0 mEq/1. After a dialysis using an acetate concentration of 25 mEq/1 HCO3 remained constant (20.4 versus 21.1 mEq/1 pre-D), whereas PCO2 fell from 35.3 to 30.8 mm Hg (P less than 0.001). Consequently PCO2 was again low relative to HCO3. Removal of CO2 by D fluid was excluded as a cause for low blood PCO2: addition of gaseous CO2 to the bath had no influence on arterial blood gases. Since post-D hypocapnia was not prevented when HCO3 was kept constant, it was concluded that post-D alkalosis cannot be the main reason for post-D hyperventilation, and that other factors related to the process of D are responsible.", "contents": "Mechanism of post dialysis hyperventilation in  patients with chronic renal insufficiency. Several hypotheses have been put forward to explain postdialysis hypocapnia. Three were tested in this study: impairment of tissue oxygenation by dialysis (D)-induced alkalosis (Bohr effect), the D disequilibrium syndrome, and the loss of carbon dioxide  (CO2) in D fluid. In 17 patients pre-DPCO2 was significantly correlated with plasma bicarbonate concentration (HCO3) and no disproportionate reduction of PCO2 was discernible. In 10 patients using a bath acetate concentration of 38 mEq/1 PCO2 was unchanged after D (35.4 versus 35.9 mm Hg before D), and was low relative to HCO3 whic increased from 21.2 to 28.0 mEq/1. After a dialysis using an acetate concentration of 25 mEq/1 HCO3 remained constant (20.4 versus 21.1 mEq/1 pre-D), whereas PCO2 fell from 35.3 to 30.8 mm Hg (P less than 0.001). Consequently PCO2 was again low relative to HCO3. Removal of CO2 by D fluid was excluded as a cause for low blood PCO2: addition of gaseous CO2 to the bath had no influence on arterial blood gases. Since post-D hypocapnia was not prevented when HCO3 was kept constant, it was concluded that post-D alkalosis cannot be the main reason for post-D hyperventilation, and that other factors related to the process of D are responsible."}
{"id": "PMID:4254", "title": "Duration of cardiac effects of timolol and propranolol.", "content": "The duration of the cardiac effects of single intravenous doses of the beta-antagonists, timolol and propranolol, was compared in 6 healthy male subjects. Timolol and propranolol were given in doses of 1 mg and 10 mg, respectively, and at specified times after their administration, beta-blockade was assessed by the reduction of maximal exercise-induced tachycardia and by the inhibition of the chronotropic and inotropic effects of isoproterenol. Inotropic effects were measured by changes in the pre-ejection period of left ventricular systole obtained from systolic time intervals. There was no statistically significant difference in the timolol and propranolol time-courses of beta-blockade. The change in exercise-tachycardia was maximal 5 min after beta-antagonist infusion but dissipated rapidly so that no statistically significant change was observed 9 hr later. The chronotropic and inotropic effects of isoproterenol were almost completely antagonized for 11/2 hr after beta-antagonist infusion, and significant beta-blockade could be demonstrated 9 hr later. There was no difference in the time-course of the negative chronotropic and inotropic effects of either beta-antagonist.", "contents": "Duration of cardiac effects of timolol and propranolol. The duration of the cardiac effects of single intravenous doses of the beta-antagonists, timolol and propranolol, was compared in 6 healthy male subjects. Timolol and propranolol were given in doses of 1 mg and 10 mg, respectively, and at specified times after their administration, beta-blockade was assessed by the reduction of maximal exercise-induced tachycardia and by the inhibition of the chronotropic and inotropic effects of isoproterenol. Inotropic effects were measured by changes in the pre-ejection period of left ventricular systole obtained from systolic time intervals. There was no statistically significant difference in the timolol and propranolol time-courses of beta-blockade. The change in exercise-tachycardia was maximal 5 min after beta-antagonist infusion but dissipated rapidly so that no statistically significant change was observed 9 hr later. The chronotropic and inotropic effects of isoproterenol were almost completely antagonized for 11/2 hr after beta-antagonist infusion, and significant beta-blockade could be demonstrated 9 hr later. There was no difference in the time-course of the negative chronotropic and inotropic effects of either beta-antagonist."}
{"id": "PMID:4255", "title": "Hypnotic efficacy of lorazepam and flurazepam.", "content": "In a double-blind crossover study involving 15 insomniac subjects, the hypnotic efficacy of lorazepam, 2 and 4 mg, was compared with flurazepam, 15 and 30 mg, and placebo. Five subjective measures were used: onset, length, and depth of sleep, number of times awakened, and satisfaction with the hypnotic. Lorazepam in 2- and 4-mg doses was comparable in hypnotic efficacy to flurazepam, 30 mg, according to most parameters of measurement. Side effects were minor, although relatively numerous at the 4-mg doses.", "contents": "Hypnotic efficacy of lorazepam and flurazepam. In a double-blind crossover study involving 15 insomniac subjects, the hypnotic efficacy of lorazepam, 2 and 4 mg, was compared with flurazepam, 15 and 30 mg, and placebo. Five subjective measures were used: onset, length, and depth of sleep, number of times awakened, and satisfaction with the hypnotic. Lorazepam in 2- and 4-mg doses was comparable in hypnotic efficacy to flurazepam, 30 mg, according to most parameters of measurement. Side effects were minor, although relatively numerous at the 4-mg doses."}
{"id": "PMID:4256", "title": "Acebultolol: basis for the prediction of effect on exercise tolerance.", "content": "Twelve unselected males suffering from documented coronary insufficiency and moderately severe angina submitted to graded multistage treadmill exercise testing on 3 separate days, 3.5 hr after a single dose of 0,200, or 400 mg of acebulolol, a cardioselective beta blocker. Control measures included random allocation of 2 patients to each of 6 balanced sequences of administration, standardized double-blind conditions, and variance analysis for Latin-square design with repeated measures on each subject. Performance was evaluated by measuring time elapsed until anginal pain, peak heart rate, peak product of heart rate and blood pressure, and peak oxygen consumption. Mean values for all criteria were significantly atered by 400 mg of acebutolol. Seven out of twelve patients were classified as responders (i.e., exercise duration increased 100% or more). The response after acebutolol was correlated with the performance on placebo in the base of exercise duration, peak heart rate, and peak product of heart rate and blood pressure. It is concluded that: (1) performance criteria are useful predictors of response to beta blockade and (2) acebutolol is a potent antianginal agent when judged by an objective treadmill exercise test.", "contents": "Acebultolol: basis for the prediction of effect on exercise tolerance. Twelve unselected males suffering from documented coronary insufficiency and moderately severe angina submitted to graded multistage treadmill exercise testing on 3 separate days, 3.5 hr after a single dose of 0,200, or 400 mg of acebulolol, a cardioselective beta blocker. Control measures included random allocation of 2 patients to each of 6 balanced sequences of administration, standardized double-blind conditions, and variance analysis for Latin-square design with repeated measures on each subject. Performance was evaluated by measuring time elapsed until anginal pain, peak heart rate, peak product of heart rate and blood pressure, and peak oxygen consumption. Mean values for all criteria were significantly atered by 400 mg of acebutolol. Seven out of twelve patients were classified as responders (i.e., exercise duration increased 100% or more). The response after acebutolol was correlated with the performance on placebo in the base of exercise duration, peak heart rate, and peak product of heart rate and blood pressure. It is concluded that: (1) performance criteria are useful predictors of response to beta blockade and (2) acebutolol is a potent antianginal agent when judged by an objective treadmill exercise test."}
{"id": "PMID:4257", "title": "Radiology in Mendelson's syndrome.", "content": "Four cases of Mendelson's syndrome (acid pulmonary aspiration) are presented. They all demonstrate an acute diffuse alveolar filling pattern. This appearance is by no means specific. However, in the absence of other causes for this pattern and of evidence of left ventricular failure the radiologist may alert the clinician to the correct diagnosis. Early recognition of this syndrome will result in prompt treatment which differs significantly from that of other causes of this radiographic appearance. The differential diagnosis is discussed.", "contents": "Radiology in Mendelson's syndrome. Four cases of Mendelson's syndrome (acid pulmonary aspiration) are presented. They all demonstrate an acute diffuse alveolar filling pattern. This appearance is by no means specific. However, in the absence of other causes for this pattern and of evidence of left ventricular failure the radiologist may alert the clinician to the correct diagnosis. Early recognition of this syndrome will result in prompt treatment which differs significantly from that of other causes of this radiographic appearance. The differential diagnosis is discussed."}
{"id": "PMID:4258", "title": "Growth hormone secretion in acid-base alterations at rest and during exercise.", "content": "1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of VO2 max. on three occasions when NH4C1, NaHCO3 or CaCO3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H+]) were measured at frequent intervals. 2. Ammonium chloride produced highest blood [H+] and NaHCO3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% VO2 max. and recovery lactic acid was highest with NaHCO3 and lowest with NH4C1. 3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH4C1 caused a variable elevation of HGH at rest and 33% VO2 max. At 66% VO2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% VO2 max., HGH was highest with NaHCO3. 4. An infusion of sodium L(+)-lactate producing plasma lactate concentrations of 3-5 mmol/l did not influence HGH secretion. 5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations.", "contents": "Growth hormone secretion in acid-base alterations at rest and during exercise. 1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of VO2 max. on three occasions when NH4C1, NaHCO3 or CaCO3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H+]) were measured at frequent intervals. 2. Ammonium chloride produced highest blood [H+] and NaHCO3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% VO2 max. and recovery lactic acid was highest with NaHCO3 and lowest with NH4C1. 3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH4C1 caused a variable elevation of HGH at rest and 33% VO2 max. At 66% VO2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% VO2 max., HGH was highest with NaHCO3. 4. An infusion of sodium L(+)-lactate producing plasma lactate concentrations of 3-5 mmol/l did not influence HGH secretion. 5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations."}
{"id": "PMID:4259", "title": "The intracellular pH of human leucocytes in response to acid-base changes in vitro.", "content": "1. Viable human leucocytes were isolated from venous blood and suspended in artificial media. Intracellular pH measurements were made by the dimethyloxazolidinedione technique in conditions simulating \"respiratory\" or \"metabolic\" acid-base disturbances. 2. Normal intracellular pH was 7-11 +/- 0-02 (mean +/- 2 SD) at an extracellular PCO2 of 5-8 kPa and a bicarbonate concentration of 25 mmol/l. 3. \"Respiratory\" and \"metabolic\" acidosis caused little change in pHi although increases in PCO2 led to relatively greater falls in pHi than did reduction in external bicarbonate concentration. 4. \"Respiratory\" and \"metabolic\" alkalosis caused similar and relatively greater increases in the pHi when compared with the response to an external acidosis.", "contents": "The intracellular pH of human leucocytes in response to acid-base changes in vitro. 1. Viable human leucocytes were isolated from venous blood and suspended in artificial media. Intracellular pH measurements were made by the dimethyloxazolidinedione technique in conditions simulating \"respiratory\" or \"metabolic\" acid-base disturbances. 2. Normal intracellular pH was 7-11 +/- 0-02 (mean +/- 2 SD) at an extracellular PCO2 of 5-8 kPa and a bicarbonate concentration of 25 mmol/l. 3. \"Respiratory\" and \"metabolic\" acidosis caused little change in pHi although increases in PCO2 led to relatively greater falls in pHi than did reduction in external bicarbonate concentration. 4. \"Respiratory\" and \"metabolic\" alkalosis caused similar and relatively greater increases in the pHi when compared with the response to an external acidosis."}
{"id": "PMID:4261", "title": "Marrow transplantation in aplastic anemia and leukemia.", "content": "Human marrow transplantation has resulted in observations of fundamental significance in understanding both aplastic anemia and acute leukemia. For example, the observation that transplanted marrow can grow successfully in patients with aplastic anemia indicates that the disease is due to a defect in the marrow precursor cells and not in the marrow microenvironment. Similarly, the observation of recurrent leukemia in donor cells has important implications. Nonetheless, marrow transplantation is sufficiently established therapeutically to be considered the treatment of choice for patients with severe aplastic anemia, and a realistic alternative for patients with recurrent acute leukemia. We suggest that patients be managed with regard to marrow transplantation according to the general approach outlined in Table 3. Marrow transplantation and histocompatibility typing are available at increasing numbers of institutions throughout the world. More and more patients with either severe aplastic anemia or recurrent acute leukemia should have marrow transplantation available to them when it is indicated as part of optimal management of these no longer hopeless diseases.", "contents": "Marrow transplantation in aplastic anemia and leukemia. Human marrow transplantation has resulted in observations of fundamental significance in understanding both aplastic anemia and acute leukemia. For example, the observation that transplanted marrow can grow successfully in patients with aplastic anemia indicates that the disease is due to a defect in the marrow precursor cells and not in the marrow microenvironment. Similarly, the observation of recurrent leukemia in donor cells has important implications. Nonetheless, marrow transplantation is sufficiently established therapeutically to be considered the treatment of choice for patients with severe aplastic anemia, and a realistic alternative for patients with recurrent acute leukemia. We suggest that patients be managed with regard to marrow transplantation according to the general approach outlined in Table 3. Marrow transplantation and histocompatibility typing are available at increasing numbers of institutions throughout the world. More and more patients with either severe aplastic anemia or recurrent acute leukemia should have marrow transplantation available to them when it is indicated as part of optimal management of these no longer hopeless diseases."}
{"id": "PMID:4287", "title": "The objective and timing of drug disposition studies, appendix V. A comparison of the bioavailability of three dosage forms of terfenadine.", "content": "Antagonistic effect against histamine-induced wheals was used to evaluate the bioavailability of terfenadine in monkeys. A rapidly dissolving tablet formulation of terfenadine shows essentially identical bioavailability to a liquid suspesion. A less readily dissolving capsule formulation lags considerably in time with regard to availability, and some question remains as to whether the total quantity in the capsule is available.", "contents": "The objective and timing of drug disposition studies, appendix V. A comparison of the bioavailability of three dosage forms of terfenadine. Antagonistic effect against histamine-induced wheals was used to evaluate the bioavailability of terfenadine in monkeys. A rapidly dissolving tablet formulation of terfenadine shows essentially identical bioavailability to a liquid suspesion. A less readily dissolving capsule formulation lags considerably in time with regard to availability, and some question remains as to whether the total quantity in the capsule is available."}
{"id": "PMID:4288", "title": "The difficult hypertensive.", "content": "With the wide range of medications available today it should be possible to obtain satisfactory control in the majority of hypertensive patients. However, there are various categories of patients who may present particular problems in management, as for example patients with cerebro-vascular and coronary disease, or with renal failure. A particularly important group is those presenting with severe resistant hypertension, and these patients may constitute about 5 to 10% of the hypertensive population. Considerations relevant to the management of patients presenting with such problems are discussed. Combined drug regimens employing clonidine or beta-blockers with peripheral vasodilators appear to be particularly useful.", "contents": "The difficult hypertensive. With the wide range of medications available today it should be possible to obtain satisfactory control in the majority of hypertensive patients. However, there are various categories of patients who may present particular problems in management, as for example patients with cerebro-vascular and coronary disease, or with renal failure. A particularly important group is those presenting with severe resistant hypertension, and these patients may constitute about 5 to 10% of the hypertensive population. Considerations relevant to the management of patients presenting with such problems are discussed. Combined drug regimens employing clonidine or beta-blockers with peripheral vasodilators appear to be particularly useful."}
{"id": "PMID:4289", "title": "[Our experience with the method of D'Amour and Smith].", "content": "The authors carried out studies on a group of analgetic preparations (morphine, lydol, thylidine, pentazocine and analgine) by the method of D Amour and Smith, using thermic painful stimulation. The experiments were carried out on white rats-young and adult of both sexes of the strain Wistar. The mean lethal dosis were determined as well as the mean effective doses and therapeutic indices. The experimental results showed that thylidine was the strongest analgetic agent with atherapeutic index of 67. The index of morphine was 63 and was close to that of thylidine, but without statistical significance. The remaining analgetic indices were with low indices: lyndiol-with 5, pentazocine - 12 and analgine - 2. The method used, according to our data, could be applied successfully on rats of both sexes, at various age groups and both strains. The method is convenient for testing analgetic activity of preparations from two basic types of analgetic agents-narcotic and nonnarcotic.", "contents": "[Our experience with the method of D'Amour and Smith]. The authors carried out studies on a group of analgetic preparations (morphine, lydol, thylidine, pentazocine and analgine) by the method of D Amour and Smith, using thermic painful stimulation. The experiments were carried out on white rats-young and adult of both sexes of the strain Wistar. The mean lethal dosis were determined as well as the mean effective doses and therapeutic indices. The experimental results showed that thylidine was the strongest analgetic agent with atherapeutic index of 67. The index of morphine was 63 and was close to that of thylidine, but without statistical significance. The remaining analgetic indices were with low indices: lyndiol-with 5, pentazocine - 12 and analgine - 2. The method used, according to our data, could be applied successfully on rats of both sexes, at various age groups and both strains. The method is convenient for testing analgetic activity of preparations from two basic types of analgetic agents-narcotic and nonnarcotic."}
{"id": "PMID:4286", "title": "Persisting and unaltered circadian rhythms of six healthy young men with a night-work shift every 48 hrs and a 2% CO2 atmosphere during a 4-week span.", "content": "Six apparently healthy young males (20 +/- 0.5 years of age) lived in a specially designed laboratory for a 1-week span in normal air, followed by 4 weeks in a 2% CO2 atmosphere and thereafter 1 week again in normal air. Room temperature was 24 degrees C. +/- 1 degrees C.; relative hygrometry 75% +/- 5%. With respect to socio-ecologic time clues and cues, the subjects were not isolated. The subjects' social synchronization was altered only by the shift-work schedule (light-on, 07(00); light-off, 22(30) on normal days). Every other day each subject had a 3-h night task, located between 23(00) and 07(00). Once a week, during 48 hrs (Saturday and Sunday) a set of physiologic variables was documented every 4 hrs in order to study their circadian changes: oral temperature, peak expiratory flow, grip strength, arterial blood pressure, tempo, and urinary pH, volume and potassium excretion. As far as rhythms are detectable (cosinor method) the most striking result is that both rhythm acrophases and amplitudes do not show any statistically significant changes when comparing either night-work versus day-work and/or normal air versus air with 2% CO2. Both 3 hrs of night-work every other day and an unusual amount of CO2 do not alter the parameters characterizing the circadian rhythms considered. The absence of desynchronization during night-work could be related to: 1) the speed of rotation in the shift-work; 2) the short duration of night-work; and 3) the youth of the subjects.", "contents": "Persisting and unaltered circadian rhythms of six healthy young men with a night-work shift every 48 hrs and a 2% CO2 atmosphere during a 4-week span. Six apparently healthy young males (20 +/- 0.5 years of age) lived in a specially designed laboratory for a 1-week span in normal air, followed by 4 weeks in a 2% CO2 atmosphere and thereafter 1 week again in normal air. Room temperature was 24 degrees C. +/- 1 degrees C.; relative hygrometry 75% +/- 5%. With respect to socio-ecologic time clues and cues, the subjects were not isolated. The subjects' social synchronization was altered only by the shift-work schedule (light-on, 07(00); light-off, 22(30) on normal days). Every other day each subject had a 3-h night task, located between 23(00) and 07(00). Once a week, during 48 hrs (Saturday and Sunday) a set of physiologic variables was documented every 4 hrs in order to study their circadian changes: oral temperature, peak expiratory flow, grip strength, arterial blood pressure, tempo, and urinary pH, volume and potassium excretion. As far as rhythms are detectable (cosinor method) the most striking result is that both rhythm acrophases and amplitudes do not show any statistically significant changes when comparing either night-work versus day-work and/or normal air versus air with 2% CO2. Both 3 hrs of night-work every other day and an unusual amount of CO2 do not alter the parameters characterizing the circadian rhythms considered. The absence of desynchronization during night-work could be related to: 1) the speed of rotation in the shift-work; 2) the short duration of night-work; and 3) the youth of the subjects."}
{"id": "PMID:4290", "title": "[Blood sugar and hypoxic dynamics in metabolic acidosis and alkalosis (experimental data)].", "content": "The dynamics of the glucose concentration and arterovenous glucose gradient was examined during different metabolic deviations in the acid-base balance. The metabolitic acidosis increased the level of sugar in the blood. A definite influence on the latter had the gravity of the acidosis and to a certain degree its pathogenetic form. The arterio-venous glucose difference changed from negative to positive with the increase of proton activity. The type of the peripheral hypoxic structure, formed  during the state of acidosis influenced both the glucose gradient and its quantitative relations to the acid-base and oxygen indices. The sugar content in the blood during metabolitic alcalosis was not changed significantly. There was an increase in the arterio-venous gradient and inverse correlation between the glucose level and the arterio-venous oxygen difference with the increase of the bicarbonate concentration.", "contents": "[Blood sugar and hypoxic dynamics in metabolic acidosis and alkalosis (experimental data)]. The dynamics of the glucose concentration and arterovenous glucose gradient was examined during different metabolic deviations in the acid-base balance. The metabolitic acidosis increased the level of sugar in the blood. A definite influence on the latter had the gravity of the acidosis and to a certain degree its pathogenetic form. The arterio-venous glucose difference changed from negative to positive with the increase of proton activity. The type of the peripheral hypoxic structure, formed  during the state of acidosis influenced both the glucose gradient and its quantitative relations to the acid-base and oxygen indices. The sugar content in the blood during metabolitic alcalosis was not changed significantly. There was an increase in the arterio-venous gradient and inverse correlation between the glucose level and the arterio-venous oxygen difference with the increase of the bicarbonate concentration."}
{"id": "PMID:4291", "title": "[Effect of beta-adrenergic blockaders on the bioelectrical activity of the mesenchephalic reticular formation].", "content": "The authors examined the beta-adrenergic structures in the mesencephalic formation (MSF) in view of establishing their role on the activity of MSF in view of establishing the in rols on the activity of MSF itself and the relationship of the same formation with the cerebral cortex and the lymbic system. It was established that beta-adrenergic blockers after their local application in MSF could inhibit its function. The data from the effect on the induced bioelectrical activity indicated also diminution in the functional activity of MSF. The authors found that the inhibiting influences of beta-blockers were abolished by their antagonist isoprenalite. An inference is made that there are beta-adrenergic structures, which act excitatory.", "contents": "[Effect of beta-adrenergic blockaders on the bioelectrical activity of the mesenchephalic reticular formation]. The authors examined the beta-adrenergic structures in the mesencephalic formation (MSF) in view of establishing their role on the activity of MSF in view of establishing the in rols on the activity of MSF itself and the relationship of the same formation with the cerebral cortex and the lymbic system. It was established that beta-adrenergic blockers after their local application in MSF could inhibit its function. The data from the effect on the induced bioelectrical activity indicated also diminution in the functional activity of MSF. The authors found that the inhibiting influences of beta-blockers were abolished by their antagonist isoprenalite. An inference is made that there are beta-adrenergic structures, which act excitatory."}
{"id": "PMID:4292", "title": "[Age-related changes in the content and characteristics of glycosaminoglycans in human aortas].", "content": "The vascular wall is rich in glucoseaminglicanes (GAG), which form the basic intercellular substance and determine its multiple functions. Using analytic and chromatographic methods the author examined hexauronic acid (HA), pentoses (P), sulphate groups and various derivatives of GAG (hyaluronic acid (HA), pentoses (P), sulphate groups and various derivatives of GAG (hyaluronic acid (HA), dermatan-sulfate (DS), keratansulfate (KS), chondroitinsulfate (HS), and cheransulfate (HES) in human aorta, obtained from persons at the age of 10 and over 70 years of age. Ten aortas of each group were examined. The studies showed that in the aortas of the adult persons the content of HA, P, HS, KS and sulphate groups was considerably higher than that of the aourtas, obtained form the young persons. There was an impression that the adult factor affected substantialy the qualitative characteristics of GAG--with advancement of age the lenght of polysaccharide chains was shortened and the degree of sulphatation was increased. The accumulation of acid GAG in the aorta of adult persons impaired the metabolism of substances between blood and tissue, which enhanced the infiltration of the blood vessels with lipids and proteins, especialy when there was a blood increase in their content (hyperlipemia, hypercholesterinemia, ect.)", "contents": "[Age-related changes in the content and characteristics of glycosaminoglycans in human aortas]. The vascular wall is rich in glucoseaminglicanes (GAG), which form the basic intercellular substance and determine its multiple functions. Using analytic and chromatographic methods the author examined hexauronic acid (HA), pentoses (P), sulphate groups and various derivatives of GAG (hyaluronic acid (HA), pentoses (P), sulphate groups and various derivatives of GAG (hyaluronic acid (HA), dermatan-sulfate (DS), keratansulfate (KS), chondroitinsulfate (HS), and cheransulfate (HES) in human aorta, obtained from persons at the age of 10 and over 70 years of age. Ten aortas of each group were examined. The studies showed that in the aortas of the adult persons the content of HA, P, HS, KS and sulphate groups was considerably higher than that of the aourtas, obtained form the young persons. There was an impression that the adult factor affected substantialy the qualitative characteristics of GAG--with advancement of age the lenght of polysaccharide chains was shortened and the degree of sulphatation was increased. The accumulation of acid GAG in the aorta of adult persons impaired the metabolism of substances between blood and tissue, which enhanced the infiltration of the blood vessels with lipids and proteins, especialy when there was a blood increase in their content (hyperlipemia, hypercholesterinemia, ect.)"}
{"id": "PMID:4293", "title": "[Beta blockers as psychotropic drugs].", "content": "The range of indications for beta blocking substances has extended to various fields of pathology : vascular system, endocrinology... The discovery of some of their side effects give good reasons to try to find out whether they should have a place in psychopharmacotherapy and wheter they could meet its present requirements.  The initial target symptoms were anxiety--which, being polymorphous, can be, at various degrees, reactionnal to obviously stressing surroundings, but which is also implied by structural distortions of personality--and psychosomatic manifestations. If their site of actions was initially thought peripherical, it now seems that their action is also central, genuinely psychotropic, anxiolytic, and non sedative, psychoanaleptic and, at the same time, stimulating and increasing the level of attention (we have observed in some cases a reduction of sleep time)--thymoanaleptic, increasing the incitement to action. On the other hand, they quiet certain excitation states caused by appearence of badly controled anxieties. This study contains three series of experiments conceived with a similar methodology.", "contents": "[Beta blockers as psychotropic drugs]. The range of indications for beta blocking substances has extended to various fields of pathology : vascular system, endocrinology... The discovery of some of their side effects give good reasons to try to find out whether they should have a place in psychopharmacotherapy and wheter they could meet its present requirements.  The initial target symptoms were anxiety--which, being polymorphous, can be, at various degrees, reactionnal to obviously stressing surroundings, but which is also implied by structural distortions of personality--and psychosomatic manifestations. If their site of actions was initially thought peripherical, it now seems that their action is also central, genuinely psychotropic, anxiolytic, and non sedative, psychoanaleptic and, at the same time, stimulating and increasing the level of attention (we have observed in some cases a reduction of sleep time)--thymoanaleptic, increasing the incitement to action. On the other hand, they quiet certain excitation states caused by appearence of badly controled anxieties. This study contains three series of experiments conceived with a similar methodology."}
{"id": "PMID:4294", "title": "Nuclear 3alpha-hydroxysteroid dehydrogenase (3alphaOHD) activity for 5alpha-dihydrotestosterone in the rat prostate.", "content": "The in vitro examination of adult male rat prostatic 3alpha-hydroxysteroid dehydrogenase (3alphaOHD) activity using 5alpha-dihydrotestosterone4 as substrate indicates that significant levels of enzyme activity are associated with purified nuclei as well as with the cytosol fractions. Both the purified nuclear and the cytosol fractions exhibited higher levels of 3alphaOHD activity with NADH than with NADPH. The pH activity curves for the NADH and NADPH catalyzed reactions were different for both the nuclear and cytosol fractions. The results suggest the presence of a number of 3alphaOHD enzymes in rat prostate.", "contents": "Nuclear 3alpha-hydroxysteroid dehydrogenase (3alphaOHD) activity for 5alpha-dihydrotestosterone in the rat prostate. The in vitro examination of adult male rat prostatic 3alpha-hydroxysteroid dehydrogenase (3alphaOHD) activity using 5alpha-dihydrotestosterone4 as substrate indicates that significant levels of enzyme activity are associated with purified nuclei as well as with the cytosol fractions. Both the purified nuclear and the cytosol fractions exhibited higher levels of 3alphaOHD activity with NADH than with NADPH. The pH activity curves for the NADH and NADPH catalyzed reactions were different for both the nuclear and cytosol fractions. The results suggest the presence of a number of 3alphaOHD enzymes in rat prostate."}
{"id": "PMID:4295", "title": "Inhibition of pancreatic islet monoamine oxidase by adrenergic antagonists and ethanol.", "content": "Although the alpha-adrenergic antagonist phentolamine potentiates glucose-stimulated insulin secretion of intact animals, it either does not alter, or it inhibits in vitro insulin secretion. This may be because in the higher concentration used in in vitro studies, phentolamine exerts a second pharmacological effect that counterbalances its primary effect of blocking monoamine action. We recently demonstrated that pancreatic islets contain substantial amounts of monoamine oxidase (MAO), and that MAO inhibitors such as iproniazid and tranylcypromine can alter insulin secretion. In the present study, we determined if other drugs that affect insulin secretion, alter the MAO activity of homogenates of rabbit pancreatic islets (collagenase technique) or liver. Phentolamine, phenoxybenzamine and propranolol (10 muM and 100 muM) inhibit islet and hepatic MAO. Haloperidol (10muM) inhibits hepatic but not islet MAO, while haloperidol (10muM) does not inhibit MAO in either tissue. Ethanol (270 to 2.7mM) inhibits islet MAO. Hepatic MAO is inhibited by high (270 to 180mM) but not by low (27 to 2.7mM) concentrations of ethanol. Collagenase digestion does not increase the sensitivity of islet and liver MAO to inhibition by phentolamine or ethanol. In the absence of added monoamines, phentolamine and phenoxybenzamine do not alter basal or glucose-stimulated insulin secretion from rabbit pancreas. Preincubation of rabbit pancreas with the serotonin precursor 5-hydroxytryptophan (5-HTP) increases the beta cell serotonin content and inhibits glucose-stimulated insulin secretion. Alpha adrenergic antagonists not only fail to block, but actually potentiate the serotonin inhibition of insulin secretion. We conclude that inhibition of islet MAO may cause an increase in islet monoamine content and these monoamines may alter in vitro insulin secretion. One mechanism through which adrenergic antagonists and ethanol modify in vitro insulin secretion may be by inhibiting pancreatic islet MAO.", "contents": "Inhibition of pancreatic islet monoamine oxidase by adrenergic antagonists and ethanol. Although the alpha-adrenergic antagonist phentolamine potentiates glucose-stimulated insulin secretion of intact animals, it either does not alter, or it inhibits in vitro insulin secretion. This may be because in the higher concentration used in in vitro studies, phentolamine exerts a second pharmacological effect that counterbalances its primary effect of blocking monoamine action. We recently demonstrated that pancreatic islets contain substantial amounts of monoamine oxidase (MAO), and that MAO inhibitors such as iproniazid and tranylcypromine can alter insulin secretion. In the present study, we determined if other drugs that affect insulin secretion, alter the MAO activity of homogenates of rabbit pancreatic islets (collagenase technique) or liver. Phentolamine, phenoxybenzamine and propranolol (10 muM and 100 muM) inhibit islet and hepatic MAO. Haloperidol (10muM) inhibits hepatic but not islet MAO, while haloperidol (10muM) does not inhibit MAO in either tissue. Ethanol (270 to 2.7mM) inhibits islet MAO. Hepatic MAO is inhibited by high (270 to 180mM) but not by low (27 to 2.7mM) concentrations of ethanol. Collagenase digestion does not increase the sensitivity of islet and liver MAO to inhibition by phentolamine or ethanol. In the absence of added monoamines, phentolamine and phenoxybenzamine do not alter basal or glucose-stimulated insulin secretion from rabbit pancreas. Preincubation of rabbit pancreas with the serotonin precursor 5-hydroxytryptophan (5-HTP) increases the beta cell serotonin content and inhibits glucose-stimulated insulin secretion. Alpha adrenergic antagonists not only fail to block, but actually potentiate the serotonin inhibition of insulin secretion. We conclude that inhibition of islet MAO may cause an increase in islet monoamine content and these monoamines may alter in vitro insulin secretion. One mechanism through which adrenergic antagonists and ethanol modify in vitro insulin secretion may be by inhibiting pancreatic islet MAO."}
{"id": "PMID:4296", "title": "Distribution of releasing factors, biogenic amines, and related enzymes in the bovine median eminence.", "content": "The bovine median eminence was dissected into eight different subdivisions: rostral, anterior internal, anterior external, middle external medial, middle external lateral, middle internal medial, middle internal lateral, and caudal. Thyrotropin-releasing hormone (TRH) was found in the highest concentrations in the middle external medial and lateral subdivisions; luteinizing hormone-releasing hormone (LHRH) was concentrated in the middle external lateral and anterior internal subdivisions. Among the various neurotransmitters and enzymes assayed, only dopamine and choline acetyltransferase were present in highest concentrations in the same subdivisions of the bovine median eminence found to be rich in TRH and LHRH. The distributions of norepinephrine, dopamine-beta-hydroxylase, serotonin, tryptophan hydroxylase, phenylethanolamine-N-methyltransferase, glutamic acid decarboxylase, and histamine appeared to correlate poorly with the major distributions of TRH and LHRH. These findings suggest that at the level of the median eminence, central neuroendocrine regulation of TRH and LHRH release may involve an interaction only with dopamine and acetylcholine.", "contents": "Distribution of releasing factors, biogenic amines, and related enzymes in the bovine median eminence. The bovine median eminence was dissected into eight different subdivisions: rostral, anterior internal, anterior external, middle external medial, middle external lateral, middle internal medial, middle internal lateral, and caudal. Thyrotropin-releasing hormone (TRH) was found in the highest concentrations in the middle external medial and lateral subdivisions; luteinizing hormone-releasing hormone (LHRH) was concentrated in the middle external lateral and anterior internal subdivisions. Among the various neurotransmitters and enzymes assayed, only dopamine and choline acetyltransferase were present in highest concentrations in the same subdivisions of the bovine median eminence found to be rich in TRH and LHRH. The distributions of norepinephrine, dopamine-beta-hydroxylase, serotonin, tryptophan hydroxylase, phenylethanolamine-N-methyltransferase, glutamic acid decarboxylase, and histamine appeared to correlate poorly with the major distributions of TRH and LHRH. These findings suggest that at the level of the median eminence, central neuroendocrine regulation of TRH and LHRH release may involve an interaction only with dopamine and acetylcholine."}
{"id": "PMID:4297", "title": "The effects of neurally active amino acids on prolactin secretion.", "content": "Several neurally active amino acids were injected into the third ventricle of anesthetized male rats. Two or eight mumole of GABA produced significant increases in the plasma concentrations of prolactin (PRL), indicating increased PRL release from the pituitary. Two mumole of glycine was also effective in elevating PRL levels. The intraventricular injection of the lowest dose of GABA (1.0 mumole), glutamate (0.4 or 2.3 mumole), lysine (0.2 or 2.0 mumole), or 0.9% NaCl did not alter PRL levels significantly. Plasma PRL concentrations did not increase following the injection of GABA or glycine directly into the anterior pituitary gland. The results suggest that GABA and glycine may play a role in the neural regulation of PRL secretion.", "contents": "The effects of neurally active amino acids on prolactin secretion. Several neurally active amino acids were injected into the third ventricle of anesthetized male rats. Two or eight mumole of GABA produced significant increases in the plasma concentrations of prolactin (PRL), indicating increased PRL release from the pituitary. Two mumole of glycine was also effective in elevating PRL levels. The intraventricular injection of the lowest dose of GABA (1.0 mumole), glutamate (0.4 or 2.3 mumole), lysine (0.2 or 2.0 mumole), or 0.9% NaCl did not alter PRL levels significantly. Plasma PRL concentrations did not increase following the injection of GABA or glycine directly into the anterior pituitary gland. The results suggest that GABA and glycine may play a role in the neural regulation of PRL secretion."}
{"id": "PMID:4298", "title": "Determination of D-3-hydroxybutyrate dehydrogenase in mouse pancreatic islets with a photokinetic technique using bacterial luciferase.", "content": "A sensitive assay for d-3hydroxybutrate dehydrogenase (EC 1.1.1.30) was developed for use with the minute amounts of material obtained from islets of Langerhans microdissected from freeze-dried pancreatic sections. NADH formed in the enzyme reaction was determined by photokinetic analysis of the luminescence obtained with bacterial luciferase from Achromobacter fishcherii. In this way, accurate determination was obtained with less than 0.1 mug dry weight of islet material. In obese hyperglycemic mice, the islet enzyme had an activity of 4.7 mumoles/min and g dry weight. Optimal enzyme activity was found at pH 8 for the islet enzyme. The enzyme activity was similar in pancreatic islets and acini, while considerably higher activity was found in cardiac muscle, liver and renal cortex. Normal mouse islets showed about equal enzyme activity as the islets from obese hyperglycemic mice.", "contents": "Determination of D-3-hydroxybutyrate dehydrogenase in mouse pancreatic islets with a photokinetic technique using bacterial luciferase. A sensitive assay for d-3hydroxybutrate dehydrogenase (EC 1.1.1.30) was developed for use with the minute amounts of material obtained from islets of Langerhans microdissected from freeze-dried pancreatic sections. NADH formed in the enzyme reaction was determined by photokinetic analysis of the luminescence obtained with bacterial luciferase from Achromobacter fishcherii. In this way, accurate determination was obtained with less than 0.1 mug dry weight of islet material. In obese hyperglycemic mice, the islet enzyme had an activity of 4.7 mumoles/min and g dry weight. Optimal enzyme activity was found at pH 8 for the islet enzyme. The enzyme activity was similar in pancreatic islets and acini, while considerably higher activity was found in cardiac muscle, liver and renal cortex. Normal mouse islets showed about equal enzyme activity as the islets from obese hyperglycemic mice."}
{"id": "PMID:4299", "title": "Human platelet glucose-6-phosphate dehydrogenase. Total purification, kinetic studies and relationship with enzyme from other blood cells.", "content": "Human platelet G-6-PD has been highly purified, to homogeneity, and its kinetic, electrophoretic and immunological characteristics have been studied. Platelet G-6-PD differs from erythrocyte or leukocyte enzymes by an increased Michaelis constant for G-6-P and a slow activity at the acid pHs. By electrofocusing only a main active band (band a) of platelet G-6-PD was found. The incubation at 37 degrees C in the presence of NADP+ and dithiothreitol normalize Km-G-6-P of platelet G-6-PD; the incubation with boiled and ultrafiltered leukemic granulocyte extracts led to an anodisation of G-6-PD active forms, a decrease of the molecular specific activity and a further increase of Km-G-6-P; these last modifications are the same as those undergone by G-6-PD incubated in crude extracts of normal or leukemic granulocytes.", "contents": "Human platelet glucose-6-phosphate dehydrogenase. Total purification, kinetic studies and relationship with enzyme from other blood cells. Human platelet G-6-PD has been highly purified, to homogeneity, and its kinetic, electrophoretic and immunological characteristics have been studied. Platelet G-6-PD differs from erythrocyte or leukocyte enzymes by an increased Michaelis constant for G-6-P and a slow activity at the acid pHs. By electrofocusing only a main active band (band a) of platelet G-6-PD was found. The incubation at 37 degrees C in the presence of NADP+ and dithiothreitol normalize Km-G-6-P of platelet G-6-PD; the incubation with boiled and ultrafiltered leukemic granulocyte extracts led to an anodisation of G-6-PD active forms, a decrease of the molecular specific activity and a further increase of Km-G-6-P; these last modifications are the same as those undergone by G-6-PD incubated in crude extracts of normal or leukemic granulocytes."}
{"id": "PMID:4300", "title": "Clinical evaluation of blood lactate levels in equine colic.", "content": "Blood lactate levels were evaluated in 36 horses (43 cases) presented with colic. A correlation between increasing blood lactate levels and decreasing percentage survival has been shown. An appreciable anion gap was found in 7 of 10 cases analyzed in detail but in each case the entire gap could not be accounted for by lactate alone. Proposals are offered to account for the unmeasured anions. Blood lactate determination is suggested as a prognostic rather than a diagnostic aid for the equine practitioner and should be used to augment other clinical findings in the horse exhibiting colic.", "contents": "Clinical evaluation of blood lactate levels in equine colic. Blood lactate levels were evaluated in 36 horses (43 cases) presented with colic. A correlation between increasing blood lactate levels and decreasing percentage survival has been shown. An appreciable anion gap was found in 7 of 10 cases analyzed in detail but in each case the entire gap could not be accounted for by lactate alone. Proposals are offered to account for the unmeasured anions. Blood lactate determination is suggested as a prognostic rather than a diagnostic aid for the equine practitioner and should be used to augment other clinical findings in the horse exhibiting colic."}
{"id": "PMID:4301", "title": "Equine viral encephalitis.", "content": "The most important neurotropic viral infections of the horse are the arthropod-borne encephalitides. These include Venezuelan encephalitis (VE), eastern encephalitis (EE) and western encephalitis (WE), which are found in the Americas, and Japanese B encephalitis which occurs in the Far East. All the viruses cause encephalitis in man. Between 1969 and 1972 an epidemic of VE occurred in Central America. In 1971 the disease was reported in Texas, where it was brought under control by the vaccination of susceptible horses with an attenuated live virus vaccine and by the reduction of the mosquito population with insecticides sprayed from aircraft. A high titre viraemia occurs with VE virus in the horse and epidemics are maintained by a mosquito/horse cycle; infection of man and other species is incidental. EE and WE have been recognised as separate diseases since 1933 and in the U.S.A. horses are protected by routine vaccination. Epidemics of these diseases are routine vaccination. Epidemics of these diseases are now uncommon. In contrast with VE, both EE and WE viruses are maintained by a bird/mosquito cycle. The viraemia in the horse is generally considered insufficient to infect mosquito vectors; the horse is a \"dead end host\". Several species of mosquito can act as vectors of VE, WE and EE. The extension of other arthropod-borne diseases to areas originally outside their geographical distribution (e.g. bluetongue in sheep) serves to illustrate the potential of VE, WE and EE to cause disease on other continents.", "contents": "Equine viral encephalitis. The most important neurotropic viral infections of the horse are the arthropod-borne encephalitides. These include Venezuelan encephalitis (VE), eastern encephalitis (EE) and western encephalitis (WE), which are found in the Americas, and Japanese B encephalitis which occurs in the Far East. All the viruses cause encephalitis in man. Between 1969 and 1972 an epidemic of VE occurred in Central America. In 1971 the disease was reported in Texas, where it was brought under control by the vaccination of susceptible horses with an attenuated live virus vaccine and by the reduction of the mosquito population with insecticides sprayed from aircraft. A high titre viraemia occurs with VE virus in the horse and epidemics are maintained by a mosquito/horse cycle; infection of man and other species is incidental. EE and WE have been recognised as separate diseases since 1933 and in the U.S.A. horses are protected by routine vaccination. Epidemics of these diseases are routine vaccination. Epidemics of these diseases are now uncommon. In contrast with VE, both EE and WE viruses are maintained by a bird/mosquito cycle. The viraemia in the horse is generally considered insufficient to infect mosquito vectors; the horse is a \"dead end host\". Several species of mosquito can act as vectors of VE, WE and EE. The extension of other arthropod-borne diseases to areas originally outside their geographical distribution (e.g. bluetongue in sheep) serves to illustrate the potential of VE, WE and EE to cause disease on other continents."}
{"id": "PMID:4302", "title": "The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K-12. Incubation of the enzyme in alkaline conditions: dissociation and disulfide-bridge formation.", "content": "Aspartokinase I - homoserine dehydrogenase I from Escherichia coli K-12, a homotetrameric enzyme, dissociates into dimers upon alkaline treatment. Both aspartokinase and homoserine dehydrogenase inactivation, as well as desensitazion towards L-threonine, occur in a multi-step process. Dithiothreitol stabilizes a dimeric form retaining full activity and sensitivity; L-homoserine stabilizing another dimeric form devoid of aspartokinase activity and retaining a substantial dehydrogenase activity insensitive toward L-threonine. A model is proposed showing that dissociation into dimers occurs in a first step, the resulting dimer losing both aspartokinase and homoserine dehydrogenase sensitivity in two subsequent steps involving the formation of intrachain disulfide bonds.", "contents": "The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K-12. Incubation of the enzyme in alkaline conditions: dissociation and disulfide-bridge formation. Aspartokinase I - homoserine dehydrogenase I from Escherichia coli K-12, a homotetrameric enzyme, dissociates into dimers upon alkaline treatment. Both aspartokinase and homoserine dehydrogenase inactivation, as well as desensitazion towards L-threonine, occur in a multi-step process. Dithiothreitol stabilizes a dimeric form retaining full activity and sensitivity; L-homoserine stabilizing another dimeric form devoid of aspartokinase activity and retaining a substantial dehydrogenase activity insensitive toward L-threonine. A model is proposed showing that dissociation into dimers occurs in a first step, the resulting dimer losing both aspartokinase and homoserine dehydrogenase sensitivity in two subsequent steps involving the formation of intrachain disulfide bonds."}
{"id": "PMID:4303", "title": "A calorimetric study of the CO Bohr effect of monomeric haemoglobins.", "content": "A calorimetric study has been made of the heats of CO reaction with the monomeric haemoglobins of Chironomus thummi thummi III and IV as a function of pH. The number of Bohr protons released at pH 7.1 was determined from heats of reaction in different buffers as 0.19 and 0.31 mol H+/mol CO for haemoglobin III and IV respectively. The heat of the Bohr ionization process was found to be 6 and 8 kcal/mol H+ (25 and 34 kJ/mol) for the haemoglobins III and IV. These values are consistent with values found for histidine groups. A pH-independent part of the reaction enthalpy was determined as - 19.7 kcal/mol CO (-82.4 kJ/mol). The same reaction with myoglobin is less exothermic. From the combination of deltaG0 and deltaH0 values TdeltaS0 values have been calculated. It was found for both haemoglobins that the entropy of reaction is greater by 2 cal K-1 mol-1 (8.4 JK-1 mol-1) at pH 9.5 as compared to pH 6.0.", "contents": "A calorimetric study of the CO Bohr effect of monomeric haemoglobins. A calorimetric study has been made of the heats of CO reaction with the monomeric haemoglobins of Chironomus thummi thummi III and IV as a function of pH. The number of Bohr protons released at pH 7.1 was determined from heats of reaction in different buffers as 0.19 and 0.31 mol H+/mol CO for haemoglobin III and IV respectively. The heat of the Bohr ionization process was found to be 6 and 8 kcal/mol H+ (25 and 34 kJ/mol) for the haemoglobins III and IV. These values are consistent with values found for histidine groups. A pH-independent part of the reaction enthalpy was determined as - 19.7 kcal/mol CO (-82.4 kJ/mol). The same reaction with myoglobin is less exothermic. From the combination of deltaG0 and deltaH0 values TdeltaS0 values have been calculated. It was found for both haemoglobins that the entropy of reaction is greater by 2 cal K-1 mol-1 (8.4 JK-1 mol-1) at pH 9.5 as compared to pH 6.0."}
{"id": "PMID:4304", "title": "Conformational studies of two non-histone chromosomal proteins and their interactions with DNA.", "content": "The conformational properties of two non-histone chromosomal proteins (high-mobility-group proteins 1 and 2) have been studied by spectroscopic methods. The interaction of high-mobility-group protein 1 with DNA has also been studied. 1. Circular dichroism results indicate that in the presence of salt both proteins are 40-50% helical between pH 1 and 9. Above pH 9 denaturation takes place. In the absence of salt the proteins denature below pH 4. 2. Nuclear magnetic resonance spectra show the presence of ring-current shifted peaks and perturbed aromatic resonances, demonstrating that the helix formation is accompanied by specific tertiary folding. 3. Nuclear magnetic resonance spectra of compelxes between high mobility group protein 1 and DNA demonstrate that a low ionic strength a portion of the molecule rich in lysine and containing all the aromatic residues is bound to DNA, whilst a more acidic region of the chain remains free from the DNA.", "contents": "Conformational studies of two non-histone chromosomal proteins and their interactions with DNA. The conformational properties of two non-histone chromosomal proteins (high-mobility-group proteins 1 and 2) have been studied by spectroscopic methods. The interaction of high-mobility-group protein 1 with DNA has also been studied. 1. Circular dichroism results indicate that in the presence of salt both proteins are 40-50% helical between pH 1 and 9. Above pH 9 denaturation takes place. In the absence of salt the proteins denature below pH 4. 2. Nuclear magnetic resonance spectra show the presence of ring-current shifted peaks and perturbed aromatic resonances, demonstrating that the helix formation is accompanied by specific tertiary folding. 3. Nuclear magnetic resonance spectra of compelxes between high mobility group protein 1 and DNA demonstrate that a low ionic strength a portion of the molecule rich in lysine and containing all the aromatic residues is bound to DNA, whilst a more acidic region of the chain remains free from the DNA."}
{"id": "PMID:4305", "title": "Succinylation of glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus. A reactive threonine residue in the apoenzyme.", "content": "1. Glyceraldehyde-3-phosphate dehydrogenase from bacillus stearothermophilus can be extensively succinylated in the presence of substrates and coenzyme without appreciable loss of activity. 2. The apoenzyme in the absence of substrates is rapidly inhibited by small amounts of succinic anhydride. NAD+, glyceraldehyde-3-phosphate and inorganic phosphate all afford protection from inhibition, and inhibition is slowly reversed in the presence of pyrophosphate at pH 8.5. 3. Kinetic and spectral studies have shown that the specific inhibition is associated with the succinylation of the aliphatic hydroxyl group of a serine or threonine residue. 4. The residue specifically succinylated has been identified as one of the two threonine residues, most probably Thr-150, adjacent to the activ-site cysteine residue in the primary structure. Its unusual reactivity is discussed in relation to the three-dimensional structure of the enzyme. 5. A second residue, a lysine homologous with Lys-212 in the pig muscle enzyme, can be succinylated in both holoenzyme and apoenzyme with no detectable effect upon the enzymic activity.", "contents": "Succinylation of glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus. A reactive threonine residue in the apoenzyme. 1. Glyceraldehyde-3-phosphate dehydrogenase from bacillus stearothermophilus can be extensively succinylated in the presence of substrates and coenzyme without appreciable loss of activity. 2. The apoenzyme in the absence of substrates is rapidly inhibited by small amounts of succinic anhydride. NAD+, glyceraldehyde-3-phosphate and inorganic phosphate all afford protection from inhibition, and inhibition is slowly reversed in the presence of pyrophosphate at pH 8.5. 3. Kinetic and spectral studies have shown that the specific inhibition is associated with the succinylation of the aliphatic hydroxyl group of a serine or threonine residue. 4. The residue specifically succinylated has been identified as one of the two threonine residues, most probably Thr-150, adjacent to the activ-site cysteine residue in the primary structure. Its unusual reactivity is discussed in relation to the three-dimensional structure of the enzyme. 5. A second residue, a lysine homologous with Lys-212 in the pig muscle enzyme, can be succinylated in both holoenzyme and apoenzyme with no detectable effect upon the enzymic activity."}
{"id": "PMID:4306", "title": "Membrane-reversible H+-ATPase from Micrococcus lysodeikticus.", "content": "Treatment of phosphorylating fragments of bacterial membrane from Micrococcus lysodeikticus with trypsin leads to increase ATPase activity. As a result of this treatment, the membrane fragments acquire the ability to transform the ATP energy into transmembrane difference in potential. Dithiothreitol has a similar effect to that of trypsin on the membrane fragments from M. lysodeikticus. Dicyclohexylcarbodimide inhibits ATPase of the membrane fragments of M. lysodeikticus, and also the ATPase-reaction-coupled generation of membrane potential. It has been suggested that the increased ATPase activity of membranes from M. lysodeikticus during treatment with trypsin and dithiothreitol is connected with the effect of these agents on the protein inhibitor of ATPase.", "contents": "Membrane-reversible H+-ATPase from Micrococcus lysodeikticus. Treatment of phosphorylating fragments of bacterial membrane from Micrococcus lysodeikticus with trypsin leads to increase ATPase activity. As a result of this treatment, the membrane fragments acquire the ability to transform the ATP energy into transmembrane difference in potential. Dithiothreitol has a similar effect to that of trypsin on the membrane fragments from M. lysodeikticus. Dicyclohexylcarbodimide inhibits ATPase of the membrane fragments of M. lysodeikticus, and also the ATPase-reaction-coupled generation of membrane potential. It has been suggested that the increased ATPase activity of membranes from M. lysodeikticus during treatment with trypsin and dithiothreitol is connected with the effect of these agents on the protein inhibitor of ATPase."}
{"id": "PMID:4307", "title": "Active-site-directed inhibition of the plasma-membrane carrier transporting short-chain, neutral amino acids into Trypanosoma brucei.", "content": "1. Glycine chloromethyl inhibited the active-transport of L-serine into bloodstream forms of Trypanosoma brucei. 2. Substrates of the short-chain, neutral amino acid transport system (N1), but not of other amino acid transport systems, protected the carrier protein from inhibition. 3. Inhibition was never more than 80% complete. The residual activity might have due to a proportion of N1 carrier active sites which had not reacted with the inhibitor. 4. The inhibition was highly selective for the N1 amino acid transport system. Other amino acid transport systems were not affected and the rate of respiration was only slightly affected. 5. The inhibition was first-order with respect to concentration, indicating that one molecule of the inhibitor reacted with each carrier active-site. 6. The high selectivity of this inhibitor should make it a useful labelling agent during the isolation and purification of the N1 amino acid transport carrier protein(s).", "contents": "Active-site-directed inhibition of the plasma-membrane carrier transporting short-chain, neutral amino acids into Trypanosoma brucei. 1. Glycine chloromethyl inhibited the active-transport of L-serine into bloodstream forms of Trypanosoma brucei. 2. Substrates of the short-chain, neutral amino acid transport system (N1), but not of other amino acid transport systems, protected the carrier protein from inhibition. 3. Inhibition was never more than 80% complete. The residual activity might have due to a proportion of N1 carrier active sites which had not reacted with the inhibitor. 4. The inhibition was highly selective for the N1 amino acid transport system. Other amino acid transport systems were not affected and the rate of respiration was only slightly affected. 5. The inhibition was first-order with respect to concentration, indicating that one molecule of the inhibitor reacted with each carrier active-site. 6. The high selectivity of this inhibitor should make it a useful labelling agent during the isolation and purification of the N1 amino acid transport carrier protein(s)."}
{"id": "PMID:4308", "title": "A quantitative model for partition in aqueous multiphase systems.", "content": "A model for the partition of charged molecules in aqueous multiphase systems has been developed. The partition coefficient of one component, or the overall partition coefficient of a number of components, between two arbitrary phases is expressed in terms of the difference in electrical potential between the phases (due to electrolytes present in the system), the net charges of the partitioned components and their partition coefficients in a (sometimes hypothetical) uncharged state. The fraction of material in one phase has also been described as a function of the net charges of the partitioned components. The model fits well to experimental data for partition of chromate, pyridine, ribonuclease A, two types of CO-hemoglobin and an enzyme mixture (yeast lysate) in three-phase systems consisting of poly(ethylene glycol), dextran, Ficoll and water. Minor deviations from the model are construed to be a pH-dependent uptake of ions. The data have also been used to detect differences in solvation of similar proteins, as well as the presence of several forms of some glycolytic enzymes present in yeast lysate.", "contents": "A quantitative model for partition in aqueous multiphase systems. A model for the partition of charged molecules in aqueous multiphase systems has been developed. The partition coefficient of one component, or the overall partition coefficient of a number of components, between two arbitrary phases is expressed in terms of the difference in electrical potential between the phases (due to electrolytes present in the system), the net charges of the partitioned components and their partition coefficients in a (sometimes hypothetical) uncharged state. The fraction of material in one phase has also been described as a function of the net charges of the partitioned components. The model fits well to experimental data for partition of chromate, pyridine, ribonuclease A, two types of CO-hemoglobin and an enzyme mixture (yeast lysate) in three-phase systems consisting of poly(ethylene glycol), dextran, Ficoll and water. Minor deviations from the model are construed to be a pH-dependent uptake of ions. The data have also been used to detect differences in solvation of similar proteins, as well as the presence of several forms of some glycolytic enzymes present in yeast lysate."}
{"id": "PMID:4309", "title": "Lysis of yeast cell walls. Lytic beta-(1 leads to 6)-glucanase from Bacillus circulans WL-12.", "content": "When grown in a mineral medium with yeast cell walls or yeast glucan as the sole carbon source, Bacillus circulans WL-12 produces wall-lytic enzymes in addition to non-lytic beta-(1 leads to 3) and beta-(1 leads to 6)-glucananases. The lytic enzymes were isolated from the culture liquid by adsorption on insoluble yeast glucan in batch operation. After digestion of the glucan, the mixture of enzymes was chromatographed on hydroxylapatite on which the lytic activity could be resolved into one lytic beta-(1 leads to 6)glucanase and two lytic beta-(1 leads to 3)-glucanase was further purified by chromatography over diethylamino-ehtyl-agarose and carboxymethyl cellulose. Its specific activity on pustulan was 6.2 units per mg of protein. The enzyme moved as a single protein with a molecular weight of 54000 during sodium dodecylsulphate electrophoresis in slab gels. Hydrolysis of pustulan went thorugh a series of oligosaccharides, leading to a mixture of gentiotriose, gentiobiose and glucose. The enzyme also produced small amounts of gentiobiose from laminarin and pachyman and on this basis its lytic activity on yeast cell walls,was attribut beta-(1 leads to 3)-linked oligosaccharides were not detected. The lytic beta-(1 leads to 6)-glucanase has an optimum pH of 6.0. Pustulan hydrolysis followed Michaelis-Menten kinetics. A Km of 0.29 mg pustulan per ml and a V of 9.1 micro-equivalents of glucose released/min per mg of enzyme were calculated. The enzyme has no metal ion requirement. The lytic beta-(1 leads to 6)-glucanase differs in essence from the non-lytic beta-(1 leads to 6)-glucanase of the same organism by its positive action on yeast cell walls and yeast glucan and its much lower specific activity on soluble pustulan.", "contents": "Lysis of yeast cell walls. Lytic beta-(1 leads to 6)-glucanase from Bacillus circulans WL-12. When grown in a mineral medium with yeast cell walls or yeast glucan as the sole carbon source, Bacillus circulans WL-12 produces wall-lytic enzymes in addition to non-lytic beta-(1 leads to 3) and beta-(1 leads to 6)-glucananases. The lytic enzymes were isolated from the culture liquid by adsorption on insoluble yeast glucan in batch operation. After digestion of the glucan, the mixture of enzymes was chromatographed on hydroxylapatite on which the lytic activity could be resolved into one lytic beta-(1 leads to 6)glucanase and two lytic beta-(1 leads to 3)-glucanase was further purified by chromatography over diethylamino-ehtyl-agarose and carboxymethyl cellulose. Its specific activity on pustulan was 6.2 units per mg of protein. The enzyme moved as a single protein with a molecular weight of 54000 during sodium dodecylsulphate electrophoresis in slab gels. Hydrolysis of pustulan went thorugh a series of oligosaccharides, leading to a mixture of gentiotriose, gentiobiose and glucose. The enzyme also produced small amounts of gentiobiose from laminarin and pachyman and on this basis its lytic activity on yeast cell walls,was attribut beta-(1 leads to 3)-linked oligosaccharides were not detected. The lytic beta-(1 leads to 6)-glucanase has an optimum pH of 6.0. Pustulan hydrolysis followed Michaelis-Menten kinetics. A Km of 0.29 mg pustulan per ml and a V of 9.1 micro-equivalents of glucose released/min per mg of enzyme were calculated. The enzyme has no metal ion requirement. The lytic beta-(1 leads to 6)-glucanase differs in essence from the non-lytic beta-(1 leads to 6)-glucanase of the same organism by its positive action on yeast cell walls and yeast glucan and its much lower specific activity on soluble pustulan."}
{"id": "PMID:4310", "title": "Lysis of yeast cell walls. Lytic beta-(1 leads to 3)-glucanases from Bacillus circulans WL-12.", "content": "Bacillus circulans WL-12 when grown in a mineral medium with yeast cell walls or yeast glucan as the soli carbon source, produced five beta-glucanases. Two beta-(1 leads to 3)-glucanases (I and II), which are lytic to yeast cell walls, were isolated from the culture liquid by batch adsorption on yeast glucan, and separated by chromatography on hydroxylapatite. Lytic beta-(1 leads to 3)-glucanase I was further purified by carboxymethylcellulose chromatography. The specific activity of lytic beta-(1 leads to 3)-glucanase I on laminarin was 4.1 U per mg of protein. The enzyme moved as a single protein with a molecular weight of 40000 during sodium dodecylsulfate electrophoresis in slab gels. It was specific for the beta-(1 leads to 3)-glucosidic bond but the enzyme did not hydrolyze laminaribiose. Hydrolysis of laminarin went through a series of oligosaccharides, and laminaribiose and glucose accumulated till the end of the reaction. A small amount of gentibiose was also produced from laminarin. Products from yeast cell walls and yeast glucan included laminaripentaose, laminaritriose, laminaribiose, glucose and gentiobiose, but no laminaritetraose was detected. This glucanase has an optimum pH of 5.5.", "contents": "Lysis of yeast cell walls. Lytic beta-(1 leads to 3)-glucanases from Bacillus circulans WL-12. Bacillus circulans WL-12 when grown in a mineral medium with yeast cell walls or yeast glucan as the soli carbon source, produced five beta-glucanases. Two beta-(1 leads to 3)-glucanases (I and II), which are lytic to yeast cell walls, were isolated from the culture liquid by batch adsorption on yeast glucan, and separated by chromatography on hydroxylapatite. Lytic beta-(1 leads to 3)-glucanase I was further purified by carboxymethylcellulose chromatography. The specific activity of lytic beta-(1 leads to 3)-glucanase I on laminarin was 4.1 U per mg of protein. The enzyme moved as a single protein with a molecular weight of 40000 during sodium dodecylsulfate electrophoresis in slab gels. It was specific for the beta-(1 leads to 3)-glucosidic bond but the enzyme did not hydrolyze laminaribiose. Hydrolysis of laminarin went through a series of oligosaccharides, and laminaribiose and glucose accumulated till the end of the reaction. A small amount of gentibiose was also produced from laminarin. Products from yeast cell walls and yeast glucan included laminaripentaose, laminaritriose, laminaribiose, glucose and gentiobiose, but no laminaritetraose was detected. This glucanase has an optimum pH of 5.5."}
{"id": "PMID:4311", "title": "Algal glyceraldehyde-3-phosphate dehydrogenase. Pyridine-nucleotide requirements of two enzymes purified from Scenedesmus obliquus.", "content": "Two enzymes with glyceraldehyde-3-phosphate dehydrogenase activity have been purified from heterotrophically grown Scenedesmus obliquus by ion-exchange chromatography and gel filtration. The D-enzyme has a molecular weight of 550000 and a VNADH: VNADPH ratio of 16 whereas the T-enzyme has a molecular weight of 140000 and a VNADH:VNADPH ratio of 0.15. The two enzymes, however, are very similar with regard to their Michaelis constants for the reduced pyridine nucleotides, pH optimum, subunit size and ultraviolet absorption.", "contents": "Algal glyceraldehyde-3-phosphate dehydrogenase. Pyridine-nucleotide requirements of two enzymes purified from Scenedesmus obliquus. Two enzymes with glyceraldehyde-3-phosphate dehydrogenase activity have been purified from heterotrophically grown Scenedesmus obliquus by ion-exchange chromatography and gel filtration. The D-enzyme has a molecular weight of 550000 and a VNADH: VNADPH ratio of 16 whereas the T-enzyme has a molecular weight of 140000 and a VNADH:VNADPH ratio of 0.15. The two enzymes, however, are very similar with regard to their Michaelis constants for the reduced pyridine nucleotides, pH optimum, subunit size and ultraviolet absorption."}
{"id": "PMID:4312", "title": "Multiple forms of cyclohexanone oxygenase from Nocardia globerula CL1.", "content": "The cyclohexanone 1,2-monooxygenase of Nocardia globerula CL1 exists as two electrophoretically distinct forms. These are present in crude cell extracts and are not artifacts of enzyme purification or electrophoresis. They have been separated in mg amounts by preparative polyacrylamide gel electrophoresis and shown to have essentially identical kinetic, spectral and physical characteristics. They do differ in pH-activity profile and temperature stability. Whether or not they are conformational isoenzymes or arise by gene duplication and divergent evolution has not been established. Cyclohexanone oxygenase constitutes 8% of the soluble protein of induced cells. This high level would correlate well with the presence of duplicate genes. It is proposed that the presence of a large amount of cyclohexanone oxygenase may confer an ecological advantage on the organism.", "contents": "Multiple forms of cyclohexanone oxygenase from Nocardia globerula CL1. The cyclohexanone 1,2-monooxygenase of Nocardia globerula CL1 exists as two electrophoretically distinct forms. These are present in crude cell extracts and are not artifacts of enzyme purification or electrophoresis. They have been separated in mg amounts by preparative polyacrylamide gel electrophoresis and shown to have essentially identical kinetic, spectral and physical characteristics. They do differ in pH-activity profile and temperature stability. Whether or not they are conformational isoenzymes or arise by gene duplication and divergent evolution has not been established. Cyclohexanone oxygenase constitutes 8% of the soluble protein of induced cells. This high level would correlate well with the presence of duplicate genes. It is proposed that the presence of a large amount of cyclohexanone oxygenase may confer an ecological advantage on the organism."}
{"id": "PMID:4313", "title": "Purification and properties of cyclopentanone oxygenase of Pseudomonas NCIB 9872.", "content": "1. Cyclopentanone oxygenase from Pseudomonas NCIB 9872 has been purified some 40-fold. It gives a single peak in the ultracentrifuge and a single major protein band on polyacrylamide gels contaminated with about 5% of a slower migrating impurity. Flavin dissociates from the protein during electrophoresis. 2. The enzyme has a molecular weight of about 200000 and is a homopolymeric assemblage of either three of four subunits of molecular weight 54000-58000. 3. The prosthetic group is FAD and values of about 2.5 are typically obtained for the number of moles bound to each mole of holoenzyme. Some FAD probably dissociates during purification and it seems likely that each subunit binds one FAD in the undamaged protein.", "contents": "Purification and properties of cyclopentanone oxygenase of Pseudomonas NCIB 9872. 1. Cyclopentanone oxygenase from Pseudomonas NCIB 9872 has been purified some 40-fold. It gives a single peak in the ultracentrifuge and a single major protein band on polyacrylamide gels contaminated with about 5% of a slower migrating impurity. Flavin dissociates from the protein during electrophoresis. 2. The enzyme has a molecular weight of about 200000 and is a homopolymeric assemblage of either three of four subunits of molecular weight 54000-58000. 3. The prosthetic group is FAD and values of about 2.5 are typically obtained for the number of moles bound to each mole of holoenzyme. Some FAD probably dissociates during purification and it seems likely that each subunit binds one FAD in the undamaged protein."}
{"id": "PMID:4314", "title": "Purification and properties of a methanol-oxidizing enzyme in Pseudomonas C.", "content": "A methanol-oxidizing enzyme has been purified from Pseudomonas C, grown on methanol as a sole source for carbon and energy. The purification procedure involved ammonium sulphate precipitation, ion-exchange chromatography and gel filtration and resulted in a yield of 35.4%. Enzyme activity can be coupled to phenazine methosulfate and requires the presence of ammonium ions in the assay mixtures. The enzymes possesses a broad specificity for primary alcohols. Formaldehyde is also oxidized by the purified enzyme. The Km value for methanol is 15 muM. The optimum pH for the oxidation of both methanol and formaldehyde is about 10.4. The enzyme has a molecular weight of about 128000 and consists of two subunits each having a molecular weight of 60000.", "contents": "Purification and properties of a methanol-oxidizing enzyme in Pseudomonas C. A methanol-oxidizing enzyme has been purified from Pseudomonas C, grown on methanol as a sole source for carbon and energy. The purification procedure involved ammonium sulphate precipitation, ion-exchange chromatography and gel filtration and resulted in a yield of 35.4%. Enzyme activity can be coupled to phenazine methosulfate and requires the presence of ammonium ions in the assay mixtures. The enzymes possesses a broad specificity for primary alcohols. Formaldehyde is also oxidized by the purified enzyme. The Km value for methanol is 15 muM. The optimum pH for the oxidation of both methanol and formaldehyde is about 10.4. The enzyme has a molecular weight of about 128000 and consists of two subunits each having a molecular weight of 60000."}
{"id": "PMID:4315", "title": "Temperature-dependent change in rate-limiting step of the magnesium-stimulated ITPase of myosin.", "content": "The effects of temperature on Mg-ITPase activity of heavy meromyosin and myosin subfragment 1 were measured in 0.1 M KC1. The initial burst of Pi liberation was one mol per mol of heavy meromyosin or two mol of myosin subfragment 1, i.e. one mol per two mol of myosin active sites, at 20 degrees C. However, it was almost zero mol below 8degrees C. Effects of KC1 concentration and pH on ITPase activity of heavy meromyosin at 20 degrees C were different from those below 8 degrees C, suggesting that the rate-limiting step in the Mg-ITP hydrolysis of myosin depends on temperature. The effect of temperature on the actin activation of heavy meromyosin Mg-ITPase was analyzed by measuring the temperature dependence of double-reciprocal plots of ITPase activity against actin concentration. The extent of actin activation was larger at low temperture. The results presented in this paper might be explained by assuming the existence of two kinds of active sites on a myosin molecule.", "contents": "Temperature-dependent change in rate-limiting step of the magnesium-stimulated ITPase of myosin. The effects of temperature on Mg-ITPase activity of heavy meromyosin and myosin subfragment 1 were measured in 0.1 M KC1. The initial burst of Pi liberation was one mol per mol of heavy meromyosin or two mol of myosin subfragment 1, i.e. one mol per two mol of myosin active sites, at 20 degrees C. However, it was almost zero mol below 8degrees C. Effects of KC1 concentration and pH on ITPase activity of heavy meromyosin at 20 degrees C were different from those below 8 degrees C, suggesting that the rate-limiting step in the Mg-ITP hydrolysis of myosin depends on temperature. The effect of temperature on the actin activation of heavy meromyosin Mg-ITPase was analyzed by measuring the temperature dependence of double-reciprocal plots of ITPase activity against actin concentration. The extent of actin activation was larger at low temperture. The results presented in this paper might be explained by assuming the existence of two kinds of active sites on a myosin molecule."}
{"id": "PMID:4316", "title": "Nuclear-magnetic-resonance study of the active-site structure of yeast phosphoglycerate kinase.", "content": "The enzyme 3-phosphoglycerate kinase from yeast has been studied by observation of the proton nuclear magnetic resonance spectrum at 270 MHz using Fourier transform techniques. Difference spectroscopy was used to enhance the resolution and to identify specific ligand binding effects and conformational changes. Perturbations involving single protons of amino-acid residues could thus be detected despite the relatively high molecular weight of the protein (47000), particularly in the aromatic (6-9 ppm) and methylene (2-3 ppm) regions of the spectrum.", "contents": "Nuclear-magnetic-resonance study of the active-site structure of yeast phosphoglycerate kinase. The enzyme 3-phosphoglycerate kinase from yeast has been studied by observation of the proton nuclear magnetic resonance spectrum at 270 MHz using Fourier transform techniques. Difference spectroscopy was used to enhance the resolution and to identify specific ligand binding effects and conformational changes. Perturbations involving single protons of amino-acid residues could thus be detected despite the relatively high molecular weight of the protein (47000), particularly in the aromatic (6-9 ppm) and methylene (2-3 ppm) regions of the spectrum."}
{"id": "PMID:4317", "title": "Fluroescence of proteins in 6-M guanidine hydrochloride. A method for the quantitative determination of tryptophan.", "content": "To determine the tryptophan content in proteins,an analytical ultraviolet fluroescence method is proposed based on making uniform the environment of aromatic chromophores in 6-7 M guanidine hydrochloride. The fluorescence intensity scale is calibrated using standard solutions of free tryptophan. A correlation coefficient between the fluorescence of protein tryptophanyl residues and of free tryptophan was estimated in testing 17 well characterized proteins. This method is particularly suited to proteins carrying groups absorbing in the 290-370 nm region, such as flavin, heme and pyridoxal phosphate and in the presence of substances such as 2-mercaptoethanol which prohibit the use of the spectroscopic or magnetic circular dichroism methods. It is less time-consuming than techniques requiring hydrolysis or chemical reactions.", "contents": "Fluroescence of proteins in 6-M guanidine hydrochloride. A method for the quantitative determination of tryptophan. To determine the tryptophan content in proteins,an analytical ultraviolet fluroescence method is proposed based on making uniform the environment of aromatic chromophores in 6-7 M guanidine hydrochloride. The fluorescence intensity scale is calibrated using standard solutions of free tryptophan. A correlation coefficient between the fluorescence of protein tryptophanyl residues and of free tryptophan was estimated in testing 17 well characterized proteins. This method is particularly suited to proteins carrying groups absorbing in the 290-370 nm region, such as flavin, heme and pyridoxal phosphate and in the presence of substances such as 2-mercaptoethanol which prohibit the use of the spectroscopic or magnetic circular dichroism methods. It is less time-consuming than techniques requiring hydrolysis or chemical reactions."}
{"id": "PMID:4318", "title": "An extracellular aminopeptidase from Clostridium histolyticum.", "content": "An aminopeptidase was isolated from the culture filtrate of Clostridium histolyticum and purified to homogeneity. Absence of endopeptidase activity in the purified preparation was demonstrated. Gel filtration on a calibrated column indicates an apparent molecular weight of 340000 for the native enzyme. Gel electrophoresis of the denatured enzyme in the presence of dodecylsulfate in constant acrylamide concentration and in a concentration gradient, resulted in the appearance of a single component for which a molecular weight of 51000 and 59000 respectively, was calculated. From mobilities of crosslinked and denatured protein species a molecular weight of 56000 was obtained for the monomer. Specificity studies show that the enzyme cleaves all types of N-terminel amino acid residues including proline and hydroxyproline from small peptides and from polypeptides. The peptide bond formed between an N-terminal amino acid residue and proline is not cleaved by the enzyme. The combined action of aminopeptidase-P and clostridal aminopeptidase leads to complete hydrolysis of the proline-rich nonapeptide bradykinin. Low rates of hydrolysis was observed for charged residues, and amides of amino acids. Kinetic studies with five tripeptides of the general structure X-Gly-Gly, where X stands for Leu, Phe, Val, Ala, or Pro, show a decrease in Km with the increasing size of the hydrophobic side chain of X. The highest Kcat values are observed with proline and alanine. In the series Pro-Gly, Pro-Gly-Pro, Pro-Gly-Pro-Pro, the last peptide is the best substrate, indicating an active site complementary to at least four amino acid residues. The enzymatic activity is dependent on the presence of divalent cations, maximal activation being reached with Mn2+ and Co2+. The optimal pH for the Mn2+ and Co2+- activated enzyme is 8.6 and 8.2 respectively. The optimal temperature is 40 degrees C. Inhibition of the aminopeptidase was achieved with Zn2+, Cu2+ and p-mercuribenzoate, but not with diisopropylphosphofluoridate.", "contents": "An extracellular aminopeptidase from Clostridium histolyticum. An aminopeptidase was isolated from the culture filtrate of Clostridium histolyticum and purified to homogeneity. Absence of endopeptidase activity in the purified preparation was demonstrated. Gel filtration on a calibrated column indicates an apparent molecular weight of 340000 for the native enzyme. Gel electrophoresis of the denatured enzyme in the presence of dodecylsulfate in constant acrylamide concentration and in a concentration gradient, resulted in the appearance of a single component for which a molecular weight of 51000 and 59000 respectively, was calculated. From mobilities of crosslinked and denatured protein species a molecular weight of 56000 was obtained for the monomer. Specificity studies show that the enzyme cleaves all types of N-terminel amino acid residues including proline and hydroxyproline from small peptides and from polypeptides. The peptide bond formed between an N-terminal amino acid residue and proline is not cleaved by the enzyme. The combined action of aminopeptidase-P and clostridal aminopeptidase leads to complete hydrolysis of the proline-rich nonapeptide bradykinin. Low rates of hydrolysis was observed for charged residues, and amides of amino acids. Kinetic studies with five tripeptides of the general structure X-Gly-Gly, where X stands for Leu, Phe, Val, Ala, or Pro, show a decrease in Km with the increasing size of the hydrophobic side chain of X. The highest Kcat values are observed with proline and alanine. In the series Pro-Gly, Pro-Gly-Pro, Pro-Gly-Pro-Pro, the last peptide is the best substrate, indicating an active site complementary to at least four amino acid residues. The enzymatic activity is dependent on the presence of divalent cations, maximal activation being reached with Mn2+ and Co2+. The optimal pH for the Mn2+ and Co2+- activated enzyme is 8.6 and 8.2 respectively. The optimal temperature is 40 degrees C. Inhibition of the aminopeptidase was achieved with Zn2+, Cu2+ and p-mercuribenzoate, but not with diisopropylphosphofluoridate."}
{"id": "PMID:4319", "title": "Ornithine carbamoyltransferase from Escherichia coli W. Purification, structure and steady-state kinetic analysis.", "content": "Ornithine carbamoyltransferase from Escherichia coli W was purified to homogeneity. The enzyme has a molecular weight of 105000. It is composed of three apparently identical subunits with molecular weights of 35000. The mechanism of the ornithine carbamoyltransferase enzyme system from E. coli W was investigated kinetically by using the approach of product inhibition and dead-end inhibition of both forward and reverse reactions. On the basis of the kinetic data and binding studies it appears that the mechanism of the reaction involves a compulsory sequence of substrate binding to the enzyme, in which carbamoylphosphate is the first substrate to bind to the enzyme and phosphate the last product to be released. The same studies also indicate that the mechanism involves dead-end complexes. The reaction mechanism appears consistent with that proposed by Theorell and Chance. Values have been determined for the Michaelis and dissociation constants involved in the combination of each reactant with the enzyme. Comparison of the values for the kinetic constants which are common to both forward and reverse reaction have shown that they are always of a comparable magnitude.", "contents": "Ornithine carbamoyltransferase from Escherichia coli W. Purification, structure and steady-state kinetic analysis. Ornithine carbamoyltransferase from Escherichia coli W was purified to homogeneity. The enzyme has a molecular weight of 105000. It is composed of three apparently identical subunits with molecular weights of 35000. The mechanism of the ornithine carbamoyltransferase enzyme system from E. coli W was investigated kinetically by using the approach of product inhibition and dead-end inhibition of both forward and reverse reactions. On the basis of the kinetic data and binding studies it appears that the mechanism of the reaction involves a compulsory sequence of substrate binding to the enzyme, in which carbamoylphosphate is the first substrate to bind to the enzyme and phosphate the last product to be released. The same studies also indicate that the mechanism involves dead-end complexes. The reaction mechanism appears consistent with that proposed by Theorell and Chance. Values have been determined for the Michaelis and dissociation constants involved in the combination of each reactant with the enzyme. Comparison of the values for the kinetic constants which are common to both forward and reverse reaction have shown that they are always of a comparable magnitude."}
{"id": "PMID:4320", "title": "Reactivity of the sulfhydryl groups of soluble succinate dehydrogenase.", "content": "Soluble succinate dehydrogenase prepared by butanol extraction reacts with N-ethylmaleimide according to first-order kinetics with respect to both remaining active enzyme and the inhibitor concentration. Binding of the sulfhydryl groups of the enzyme prevents its alkylation by N-ethylmaleimide and inhibition by oxaloacetate. A kinetic analysis of the inactivation of alkylating reagent in the presence of succinate or malonate suggests that N-ethylmaleimide acts as a site-directed inhibitor. The apparent first-order rate constant of alkylation increases between pH 5.8 and 7.8 indicating a pKa value for the enzyme sulfhydryl group equal to 7.0 at 22 degrees C in 50 mM Tris-sufate buffer. Certain anions (phosphate, citrate, maleate and acetate) decrease the reactivity of the enzyme towards the alkylating reagent. Succinate/phenazine methosulfate reductase activity measured in the presence of a saturating concentration of succinate shows the same pH-dependence as the alkylation rate by N-ethylmaleimide. The mechanism of the first step of succinate oxidation, including a nucleophilic attack of substrate by the active-site sulfhydryl group, is discussed.", "contents": "Reactivity of the sulfhydryl groups of soluble succinate dehydrogenase. Soluble succinate dehydrogenase prepared by butanol extraction reacts with N-ethylmaleimide according to first-order kinetics with respect to both remaining active enzyme and the inhibitor concentration. Binding of the sulfhydryl groups of the enzyme prevents its alkylation by N-ethylmaleimide and inhibition by oxaloacetate. A kinetic analysis of the inactivation of alkylating reagent in the presence of succinate or malonate suggests that N-ethylmaleimide acts as a site-directed inhibitor. The apparent first-order rate constant of alkylation increases between pH 5.8 and 7.8 indicating a pKa value for the enzyme sulfhydryl group equal to 7.0 at 22 degrees C in 50 mM Tris-sufate buffer. Certain anions (phosphate, citrate, maleate and acetate) decrease the reactivity of the enzyme towards the alkylating reagent. Succinate/phenazine methosulfate reductase activity measured in the presence of a saturating concentration of succinate shows the same pH-dependence as the alkylation rate by N-ethylmaleimide. The mechanism of the first step of succinate oxidation, including a nucleophilic attack of substrate by the active-site sulfhydryl group, is discussed."}
{"id": "PMID:4321", "title": "Identification and properties of 8-hydroxyflavin--adenine dinucleotide in electron-transferring flavoprotein from Peptostreptococcus elsdenii.", "content": "1. A new flavin prosthetic group has been isolated in pure form from the electron-transferring flavoprotein of Peptostreptococcus elsdenni. Its structure has been established as the FAD derivative of 7-methyl-8-hydroxyisoalloxazine: (see article). Proof of this structure has been obtained by chemical syntehsis of 7-methyl-8-hydroxyisoalloxazine models, and by stepwise degradation of the native compound to 7-methy-8-hydroxyalloxazine. The orange chromophore is characterized by a strong absorption band with a maximum at 472 nm (xi = 41 000 M-1 CM-1) and a pK at 4.8 due to the ionisation of the C(8)-OH group. 2. The properties of a series of functionally substituted derivatives of 8-hydroxy flavins and lumichromes have been investigated to provide a basis for interpreting the effects of pH on the spectroscopic properties of the 8-hydroxy derivatives of FAD and FMN. 3. The 8-hydroxy derivative of FAD is bound by apo-D-amino acid oxidase; the complex shows no catalytic activity. The 8-hydroxy derivative of FMN is bound by apoflavodoxin to give a complex which has catalytic activity similar to that of native flavodoxin. The complex is reversibly reduced by dithionite, first to a relatively stable semiquinone and further to the dihydroflavin form.", "contents": "Identification and properties of 8-hydroxyflavin--adenine dinucleotide in electron-transferring flavoprotein from Peptostreptococcus elsdenii. 1. A new flavin prosthetic group has been isolated in pure form from the electron-transferring flavoprotein of Peptostreptococcus elsdenni. Its structure has been established as the FAD derivative of 7-methyl-8-hydroxyisoalloxazine: (see article). Proof of this structure has been obtained by chemical syntehsis of 7-methyl-8-hydroxyisoalloxazine models, and by stepwise degradation of the native compound to 7-methy-8-hydroxyalloxazine. The orange chromophore is characterized by a strong absorption band with a maximum at 472 nm (xi = 41 000 M-1 CM-1) and a pK at 4.8 due to the ionisation of the C(8)-OH group. 2. The properties of a series of functionally substituted derivatives of 8-hydroxy flavins and lumichromes have been investigated to provide a basis for interpreting the effects of pH on the spectroscopic properties of the 8-hydroxy derivatives of FAD and FMN. 3. The 8-hydroxy derivative of FAD is bound by apo-D-amino acid oxidase; the complex shows no catalytic activity. The 8-hydroxy derivative of FMN is bound by apoflavodoxin to give a complex which has catalytic activity similar to that of native flavodoxin. The complex is reversibly reduced by dithionite, first to a relatively stable semiquinone and further to the dihydroflavin form."}
{"id": "PMID:4322", "title": "Kinetics of reassociation and reactivation of pig-muscle lactic dehydrogenase after acid dissociation.", "content": "Lactic dehydrogenase from pig skeletal muscle (M4) can be reversibly dissociated to the monomer at pH 4-5 depending on the anion applied. Using identical experimental conditions the pH-depending profiles of dissociation, denaturation, and deactivation coincide with each other. Deviations in the pH-dependence of protein fluorescence reflect changes in the microenvironment of specific chromophores rather than significant differences in the structure-function relationship as pH is changed. The dissociation state is characterized by the homogeneous inactive monomer of 35000. The reassociated material consists of up to 85% fully active tetramers, indistinguishable from the initial native enzymes, as shown by hydrodynamic, spectroscopic and enzymic properties. The rest represents a mixture of irreversibly denatured high aggregates. Under optimum conditions of reactivation both recovery of enzymic activity and native fluorescence obey strict second order kinetics with an activation energy of 44 kcal/mol (184 kJ/mol). NAD+ and NADH do not show any significant influence on the yield and kinetics of the refolding process and the recovery of enzymic activity. The kinetic results suggest the reassociation of inactive monomers to be rate-limiting in the refolding and reactivation processes being considered.", "contents": "Kinetics of reassociation and reactivation of pig-muscle lactic dehydrogenase after acid dissociation. Lactic dehydrogenase from pig skeletal muscle (M4) can be reversibly dissociated to the monomer at pH 4-5 depending on the anion applied. Using identical experimental conditions the pH-depending profiles of dissociation, denaturation, and deactivation coincide with each other. Deviations in the pH-dependence of protein fluorescence reflect changes in the microenvironment of specific chromophores rather than significant differences in the structure-function relationship as pH is changed. The dissociation state is characterized by the homogeneous inactive monomer of 35000. The reassociated material consists of up to 85% fully active tetramers, indistinguishable from the initial native enzymes, as shown by hydrodynamic, spectroscopic and enzymic properties. The rest represents a mixture of irreversibly denatured high aggregates. Under optimum conditions of reactivation both recovery of enzymic activity and native fluorescence obey strict second order kinetics with an activation energy of 44 kcal/mol (184 kJ/mol). NAD+ and NADH do not show any significant influence on the yield and kinetics of the refolding process and the recovery of enzymic activity. The kinetic results suggest the reassociation of inactive monomers to be rate-limiting in the refolding and reactivation processes being considered."}
{"id": "PMID:4323", "title": "Alkylation of estradiol 17beta-dehydrogenase from human placenta with 3-chloroacetylpyridine--adenine dinucleotide.", "content": "3-Chloroacetylpyridine--adenine dinucleotide, which is active as a hydride acceptor (Km = 0.6 mM), inactivates and alkylates estradiol 17beta-dehydrogenase. The kinetics of inactivation by 3-chloroacetylpyridine--adenine dinucleotide and the absence of inactivation by 3-chloroacetylpyridine ribose phosphate show that the alkylation follows the formation of a binary complex (Kd = 4.5 X 10(-4) M). Studies of the labelling by 3-chloro[2-14C]acetylpyridine--adenine dinucleotide and the rate of alkylation as a function of pH, give evidence to the alkylation of a cysteine, the stoichiometry being one mole per subunit. The 14C label is distributed between three chymotryptic peptides, one of which accounts for about 50% of the radioactive label.", "contents": "Alkylation of estradiol 17beta-dehydrogenase from human placenta with 3-chloroacetylpyridine--adenine dinucleotide. 3-Chloroacetylpyridine--adenine dinucleotide, which is active as a hydride acceptor (Km = 0.6 mM), inactivates and alkylates estradiol 17beta-dehydrogenase. The kinetics of inactivation by 3-chloroacetylpyridine--adenine dinucleotide and the absence of inactivation by 3-chloroacetylpyridine ribose phosphate show that the alkylation follows the formation of a binary complex (Kd = 4.5 X 10(-4) M). Studies of the labelling by 3-chloro[2-14C]acetylpyridine--adenine dinucleotide and the rate of alkylation as a function of pH, give evidence to the alkylation of a cysteine, the stoichiometry being one mole per subunit. The 14C label is distributed between three chymotryptic peptides, one of which accounts for about 50% of the radioactive label."}
{"id": "PMID:4324", "title": "Regulation of respiration and nitrogen fixation in different types of Azotobacter vinelandii.", "content": "The levels of the adenine nucleotides, pyridine nucleotides and the kinetical parameters of the enzymes of the Entner-Doudoroff pathway (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) were determined in Azotobacter vinelandii cells, grown under O2- or N2-limiting conditions. It was concluced that the levels of both the adenine nucleotides and pyridine nucleotides do not limit the rate of sucrose oxidation. Experiments with radioactive pyruvate and sucrose show that the rate of sucrose oxidation of Azotobacter cells is associated with an increase in the rate of sucrose uptake. The sites of oxidative phosphorylation and the composition of the respiratory membranes with respect to cytochromes c4 + c5, b and d differ in cells growth either O2- or N2-limited. It was possible to show that the respiration protection of the nitrogen-fixing system in Azotobacter is mainly independent of the oxidation capacity of the cells. The oxidation capacity intrinsically depends on the type of substrate and can be partly adapted. The maximum activity of the nitrogenase in Azotobacter depends on the type of substrate oxidized. Although the level of energy charge is somewhat dependent on the type of substrate used, no obvious relation can be derived between changes in energy charge and nitrogenase activity. An alternative proposal is given.", "contents": "Regulation of respiration and nitrogen fixation in different types of Azotobacter vinelandii. The levels of the adenine nucleotides, pyridine nucleotides and the kinetical parameters of the enzymes of the Entner-Doudoroff pathway (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) were determined in Azotobacter vinelandii cells, grown under O2- or N2-limiting conditions. It was concluced that the levels of both the adenine nucleotides and pyridine nucleotides do not limit the rate of sucrose oxidation. Experiments with radioactive pyruvate and sucrose show that the rate of sucrose oxidation of Azotobacter cells is associated with an increase in the rate of sucrose uptake. The sites of oxidative phosphorylation and the composition of the respiratory membranes with respect to cytochromes c4 + c5, b and d differ in cells growth either O2- or N2-limited. It was possible to show that the respiration protection of the nitrogen-fixing system in Azotobacter is mainly independent of the oxidation capacity of the cells. The oxidation capacity intrinsically depends on the type of substrate and can be partly adapted. The maximum activity of the nitrogenase in Azotobacter depends on the type of substrate oxidized. Although the level of energy charge is somewhat dependent on the type of substrate used, no obvious relation can be derived between changes in energy charge and nitrogenase activity. An alternative proposal is given."}
{"id": "PMID:4325", "title": "The proton electrochemical gradient in Escherichia coli cells.", "content": "The internal pH of Escherichia coli cells was estimated from the distribution of either 5,5-[14C]dimethyl-2,4-oxazolidinedione or [14C]methylamine. EDTA/valinomycin treatment of cells was employed to estimate delta psi from 86Rb+ distribution concomitant with the delta pH for calculation of delta muH. Respiring intact cells maintained an internal pH more alkaline by 0.63-0.75 unit than that of the milieu at extracellular pH 7, both in growth medium and KCl solutions. The delta pH decreased when respiration was inhibited by anaerobiosis or in the presence of KCN. The delta muH, established by EDTA/valinomycin-treated cells, was constant (122-129 mV) over extracellular potassium concentration of 0.01 mM-1 mM. At the lower potassium concentration delta psi (110-120 mV) was the predominant component, and at the higher concentration delta pH increased to 0.7 units (42 mV). At 150 mM potassium delta muH was reduced to 70 mV mostly due to a delta pH component of 0.89 (53 mV). The interchangeability of the delta muH components is consistent with an electronic proton pump and with potassium serving as a counter ion in the presence of valinomycin. Indeed both parameters of delta muH decreased in the presence of carbonylcyanide p-trifluoromethoxyphenylhydrazone. The highest delta pH of 2 units was observed in the intact cells at pH 6; increasing the extracellular pH decreased the delta pH to 0 at pH 7.65 and to -0.51 at pH 9. A similar pattern of dependence of delta pH on extracellular pH was observed in EDTA/valinomycin-treated cells but the delta psi was almost constant over the whole range of extracellular pH values (6-8) implying electroneutral proton movement. Potassium is specifically required for respiration of EDTA-treated E. coli K12 cells since other monovalent or divalent cations could not replace potassium and valinomycin was not required.", "contents": "The proton electrochemical gradient in Escherichia coli cells. The internal pH of Escherichia coli cells was estimated from the distribution of either 5,5-[14C]dimethyl-2,4-oxazolidinedione or [14C]methylamine. EDTA/valinomycin treatment of cells was employed to estimate delta psi from 86Rb+ distribution concomitant with the delta pH for calculation of delta muH. Respiring intact cells maintained an internal pH more alkaline by 0.63-0.75 unit than that of the milieu at extracellular pH 7, both in growth medium and KCl solutions. The delta pH decreased when respiration was inhibited by anaerobiosis or in the presence of KCN. The delta muH, established by EDTA/valinomycin-treated cells, was constant (122-129 mV) over extracellular potassium concentration of 0.01 mM-1 mM. At the lower potassium concentration delta psi (110-120 mV) was the predominant component, and at the higher concentration delta pH increased to 0.7 units (42 mV). At 150 mM potassium delta muH was reduced to 70 mV mostly due to a delta pH component of 0.89 (53 mV). The interchangeability of the delta muH components is consistent with an electronic proton pump and with potassium serving as a counter ion in the presence of valinomycin. Indeed both parameters of delta muH decreased in the presence of carbonylcyanide p-trifluoromethoxyphenylhydrazone. The highest delta pH of 2 units was observed in the intact cells at pH 6; increasing the extracellular pH decreased the delta pH to 0 at pH 7.65 and to -0.51 at pH 9. A similar pattern of dependence of delta pH on extracellular pH was observed in EDTA/valinomycin-treated cells but the delta psi was almost constant over the whole range of extracellular pH values (6-8) implying electroneutral proton movement. Potassium is specifically required for respiration of EDTA-treated E. coli K12 cells since other monovalent or divalent cations could not replace potassium and valinomycin was not required."}
{"id": "PMID:4326", "title": "[Spectral properties of porcine plasminogen: study of the acidic transition (author's transl)].", "content": "The acidic transition of porcine plasminogen, prepared by affinity chromatography, was studied by non-destructive methods. These methods are based on the analysis of the behaviour of the tryptophyls under various conditions. The perturbation of the absorption and emission spectra by pH or temperature and the dynamic quenching of the intrinsic fluorescence are used to obtain information on structural changes which affect the environment of these residues. It is shown that by decreasing pH the fluorescence emission spectra are shifted toward the long wavelengths, with a broadening of the fluorescence band. The same effect can be obtained at constant pH by heating the protein solution. In order to analyze these phenomena, it is assumed that the fluorescence intensities at 355 nm and 328 nm reflect the proportion of the tryptophans which are exposed to the solvent, and buried, respectively. The plot of the ratio of the fluorescence intensities at these wavelengths versus pH or temperature leads to a titration curve showing an unmasking of tryptophans. The proportion of exposed tryptophans is measured by the dynamic fluorescence quenching technique and the data analyzed according to Lehrer. The plot of the fraction of exposed tryptophyls versus pH also shows the unmasking of these chromophores. Thermal perturbation of a solution of plaminogen at neutral pH induces a difference absorption spectrum whose amplitudes at the maxima are proportional to the number of exposed aromatic residues. The comparison with a solution of fully denatured plasminogen in 6 M guanidium chloride, where all the tryptophyls are exposed, shows that the percentage of exposure is equal to 59%. This number is significantly higher than the percentage found by the fluorescence quenching technique (20%), indicating that some tryptophyls are located in crevices, exposed to the solvent but not to the iodide. At acidic pH the absorption difference spectra induced by thermal perturbation are not classical, since they show an inversion and a new band between 300 nm and 305 nm. This band is mentioned in the literature as a minor band of tryptophan which appears when this chromophore is located in an asymmetric environment. On plotting the maximum amplitude of these spectra obtained at acidic pH versus temperature, we obtain a curve indicating that two types of antagonistic interactions are involved in the perturbation of the chromophores spectra. The spectrophotometric titration of plasminogen gives classical absorption difference spectra. By plotting the maximum amplitude at 292 nm versus pH, we obtain a titration curve with an apparent pK of 2.9 units. This pK is acidic which respect to the pK value of a normal carboxyl. This low value can be due to a positively charged group in the neighbourhood of a carboxyl, which interacts with one or more chromophores. When the carboxyl becomes protonated, this positively charged group is free and available to perturb the environment of some chromophores...", "contents": "[Spectral properties of porcine plasminogen: study of the acidic transition (author's transl)]. The acidic transition of porcine plasminogen, prepared by affinity chromatography, was studied by non-destructive methods. These methods are based on the analysis of the behaviour of the tryptophyls under various conditions. The perturbation of the absorption and emission spectra by pH or temperature and the dynamic quenching of the intrinsic fluorescence are used to obtain information on structural changes which affect the environment of these residues. It is shown that by decreasing pH the fluorescence emission spectra are shifted toward the long wavelengths, with a broadening of the fluorescence band. The same effect can be obtained at constant pH by heating the protein solution. In order to analyze these phenomena, it is assumed that the fluorescence intensities at 355 nm and 328 nm reflect the proportion of the tryptophans which are exposed to the solvent, and buried, respectively. The plot of the ratio of the fluorescence intensities at these wavelengths versus pH or temperature leads to a titration curve showing an unmasking of tryptophans. The proportion of exposed tryptophans is measured by the dynamic fluorescence quenching technique and the data analyzed according to Lehrer. The plot of the fraction of exposed tryptophyls versus pH also shows the unmasking of these chromophores. Thermal perturbation of a solution of plaminogen at neutral pH induces a difference absorption spectrum whose amplitudes at the maxima are proportional to the number of exposed aromatic residues. The comparison with a solution of fully denatured plasminogen in 6 M guanidium chloride, where all the tryptophyls are exposed, shows that the percentage of exposure is equal to 59%. This number is significantly higher than the percentage found by the fluorescence quenching technique (20%), indicating that some tryptophyls are located in crevices, exposed to the solvent but not to the iodide. At acidic pH the absorption difference spectra induced by thermal perturbation are not classical, since they show an inversion and a new band between 300 nm and 305 nm. This band is mentioned in the literature as a minor band of tryptophan which appears when this chromophore is located in an asymmetric environment. On plotting the maximum amplitude of these spectra obtained at acidic pH versus temperature, we obtain a curve indicating that two types of antagonistic interactions are involved in the perturbation of the chromophores spectra. The spectrophotometric titration of plasminogen gives classical absorption difference spectra. By plotting the maximum amplitude at 292 nm versus pH, we obtain a titration curve with an apparent pK of 2.9 units. This pK is acidic which respect to the pK value of a normal carboxyl. This low value can be due to a positively charged group in the neighbourhood of a carboxyl, which interacts with one or more chromophores. When the carboxyl becomes protonated, this positively charged group is free and available to perturb the environment of some chromophores..."}
{"id": "PMID:4327", "title": "Comparison of the metal-ion-promoted dephosphorylation of the 5'-triphosphates of adenosine, inosine, guanosine and cytidine by Mn2+, Ni2+ and Zn2+ in binary and ternary complexes.", "content": "The dependence of the rate of dephosphorylation of ATP, ITP, GTP and CTP (= NTP), expressed as first-order rate constants (50 degrees C; I = 0.1 M, NaClO4), on pH (2 to 10), in the absence and presence of Mn2+, Ni2+, and Zn2+, was investigated. The reaction is accelerated by Zn2+ and passes through a pH optimum at about 8 for the system Zn2+-ATP or 9 for Zn2+-ITP and Zn2+-GTP; this is analogous to observations made earlier with the corresponding Cu2+ systems. By computing the pH dependence of the distribution of the several species present in these systems it is shown that the highest rates are observed in the pH regions where the concentration of Zn(ATP)2-, Zn(ITP-H)3-, or Zn(GTP-H)3- dominates. By evaluating the pH dependence evidence is given that the attacking nucleophile is OH- or H2O for Zn (ATP)2- and H2O for Zn (ITP-H)3- or Zn(GTP-H)3-. For all these complexes metal-ion/nucleic-base interactions are known, leading to the formation of macrochelates. These metal-ion/nucleic-base interactions are crucial for the observation of a metal-ion-promoted dephosphorylation; in agreement with this, and the small tendency of the cytosine moiety to coordinate, the CTP systems are rather stable towards dephosphorylation. It should be noted that these experimental results do not necessarily mean that the macrochelates usually described are the reactive complexes, but only that the active complex must be closely related to them (e.g. isomers, etc). Although for the Ni2+ systems with ATP, ITP, and GTP, and for the Mn2+-ATP system a metal-ion/nucleic-base interaction is also known, these systems are not very sensitive to hydrolytic cleavage of the terminal P-O-P bond. The only known significant structural difference between the Ni2+-NTP or the Mn2+-ATP complexes and those of Cu2+ or Zn2+ is that Ni2+ Mn2+ coordinate to all three phsophate groups, whereas Cu2+ and Zn2+ involve only the beta and gamma ones. This structure-reactivity relationship is rationalized by the suggestion that in the active species the metal ion should be coordinated to the alpha,beta-phosphate groups leaving the gamma-group open to nucleophilic attack. Obviously, an initial beta,gamma-coordination is suitable for a shift of the metal ion along the phosphate back-bone into the reactive alpha-beta-position, while for an alpha,beta,gamma-coordination only the less favorable removal of the coordinated gamma-group remains. The metal-ion/nucleic-base interaction is considered as being important for achieving this reactive structure. The connection between trans-phosphorylation in vitro and in vivo is discussed. It is also shown that the formation of mixed-ligand or ternary complexes inhibits the dephosphorylation process. This is on the one hand of interest with regard to the transport of hydrolysis-sensitive phosphates in nature, while on the other it casts doubts on conclusions based on experiments carried out in the presence of buffers, because these contain weak bases and hence potential ligands.", "contents": "Comparison of the metal-ion-promoted dephosphorylation of the 5'-triphosphates of adenosine, inosine, guanosine and cytidine by Mn2+, Ni2+ and Zn2+ in binary and ternary complexes. The dependence of the rate of dephosphorylation of ATP, ITP, GTP and CTP (= NTP), expressed as first-order rate constants (50 degrees C; I = 0.1 M, NaClO4), on pH (2 to 10), in the absence and presence of Mn2+, Ni2+, and Zn2+, was investigated. The reaction is accelerated by Zn2+ and passes through a pH optimum at about 8 for the system Zn2+-ATP or 9 for Zn2+-ITP and Zn2+-GTP; this is analogous to observations made earlier with the corresponding Cu2+ systems. By computing the pH dependence of the distribution of the several species present in these systems it is shown that the highest rates are observed in the pH regions where the concentration of Zn(ATP)2-, Zn(ITP-H)3-, or Zn(GTP-H)3- dominates. By evaluating the pH dependence evidence is given that the attacking nucleophile is OH- or H2O for Zn (ATP)2- and H2O for Zn (ITP-H)3- or Zn(GTP-H)3-. For all these complexes metal-ion/nucleic-base interactions are known, leading to the formation of macrochelates. These metal-ion/nucleic-base interactions are crucial for the observation of a metal-ion-promoted dephosphorylation; in agreement with this, and the small tendency of the cytosine moiety to coordinate, the CTP systems are rather stable towards dephosphorylation. It should be noted that these experimental results do not necessarily mean that the macrochelates usually described are the reactive complexes, but only that the active complex must be closely related to them (e.g. isomers, etc). Although for the Ni2+ systems with ATP, ITP, and GTP, and for the Mn2+-ATP system a metal-ion/nucleic-base interaction is also known, these systems are not very sensitive to hydrolytic cleavage of the terminal P-O-P bond. The only known significant structural difference between the Ni2+-NTP or the Mn2+-ATP complexes and those of Cu2+ or Zn2+ is that Ni2+ Mn2+ coordinate to all three phsophate groups, whereas Cu2+ and Zn2+ involve only the beta and gamma ones. This structure-reactivity relationship is rationalized by the suggestion that in the active species the metal ion should be coordinated to the alpha,beta-phosphate groups leaving the gamma-group open to nucleophilic attack. Obviously, an initial beta,gamma-coordination is suitable for a shift of the metal ion along the phosphate back-bone into the reactive alpha-beta-position, while for an alpha,beta,gamma-coordination only the less favorable removal of the coordinated gamma-group remains. The metal-ion/nucleic-base interaction is considered as being important for achieving this reactive structure. The connection between trans-phosphorylation in vitro and in vivo is discussed. It is also shown that the formation of mixed-ligand or ternary complexes inhibits the dephosphorylation process. This is on the one hand of interest with regard to the transport of hydrolysis-sensitive phosphates in nature, while on the other it casts doubts on conclusions based on experiments carried out in the presence of buffers, because these contain weak bases and hence potential ligands."}
{"id": "PMID:4328", "title": "Rat-liver superoxide dismutase. Purification and age-related modifications.", "content": "Cytoplasmic superoxide dismutase has been purified from livers of young (6 months) and old (27 months) rats. The enzyme purified from old animals shows an age-related reduction in the specific activity, accumulation of antigenically cross-reacting material and increased sensitivity to temperature. No differences were found in the molecular weight, electrophoretic mobility, antigenicity and Ki between enzymes purified from young and old rats. This is the first demonstration of age-related alterations in a purified form of a non-metabolic enzyme, which can be related to reduced activity. The possible role of this reduced activity in age-dependent deterioration of cellular functions is discussed.", "contents": "Rat-liver superoxide dismutase. Purification and age-related modifications. Cytoplasmic superoxide dismutase has been purified from livers of young (6 months) and old (27 months) rats. The enzyme purified from old animals shows an age-related reduction in the specific activity, accumulation of antigenically cross-reacting material and increased sensitivity to temperature. No differences were found in the molecular weight, electrophoretic mobility, antigenicity and Ki between enzymes purified from young and old rats. This is the first demonstration of age-related alterations in a purified form of a non-metabolic enzyme, which can be related to reduced activity. The possible role of this reduced activity in age-dependent deterioration of cellular functions is discussed."}
{"id": "PMID:4330", "title": "Effects of ouabain and hypoxia on the cardiac stimulation threshold in the dog (with special reference to changes in extra- and intracellular potassium concentrations).", "content": "The influence on the cardiac stimulation threshold of changes in the myocardial intra/extracellular potassium ratio induced with ouabain and hypoxia was investigated in 9 dogs with total atrioventricular block. In spite of significant elevations of extracellular potassium and reductions of intracellular potassium significant changes in stimulation threshold were not seen. It is suggested that different experimental conditions are responsible for the great variations in the results of previous studies of this subject.", "contents": "Effects of ouabain and hypoxia on the cardiac stimulation threshold in the dog (with special reference to changes in extra- and intracellular potassium concentrations). The influence on the cardiac stimulation threshold of changes in the myocardial intra/extracellular potassium ratio induced with ouabain and hypoxia was investigated in 9 dogs with total atrioventricular block. In spite of significant elevations of extracellular potassium and reductions of intracellular potassium significant changes in stimulation threshold were not seen. It is suggested that different experimental conditions are responsible for the great variations in the results of previous studies of this subject."}
{"id": "PMID:4331", "title": "The effect of fructose infusions on the oxygen transport system of human blood.", "content": "In 9 healthy subjects the erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration, which modifies the oxygen affinity of haemoglobin, decreased by more than 25 per cent within 60 minutes of the beginning of a fructose infusion (0.5 g.kg body weight-1.h-1). In contrast erythrocyte adenosine triphosphate (ATP) concentration was unchanged. In spite of the diminished 2,3-DPG concentrations the oxygen affinity of whole blood actually measured remained unaltered. However, at the same time both the arterial and the venous blood pH had fallen by 0.05 or more. In vitro experiments indicated that this fall of erythrocyte 2,3-DPG was not due to a direct effect of fructose on the intra-erythrocytic regulation of 2,3-DPG or to changes indirectly related to the intravenous administration of fructose in vivo, i.e. an increase of the blood lactate/pyruvate ratio or a decrease of plasma inorganic phosphate. It is suggested that two opposing effects on the oxygen transport system of blood are induced by fructose infusions: 1) a displacement of the oxygen dissociation curve to the right due to the Bohr effect 2) a virtually counterbalancing shift of the oxygen dissociation curve to the left due to decreased erythrocyte 2,3-DPG concentrations.", "contents": "The effect of fructose infusions on the oxygen transport system of human blood. In 9 healthy subjects the erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration, which modifies the oxygen affinity of haemoglobin, decreased by more than 25 per cent within 60 minutes of the beginning of a fructose infusion (0.5 g.kg body weight-1.h-1). In contrast erythrocyte adenosine triphosphate (ATP) concentration was unchanged. In spite of the diminished 2,3-DPG concentrations the oxygen affinity of whole blood actually measured remained unaltered. However, at the same time both the arterial and the venous blood pH had fallen by 0.05 or more. In vitro experiments indicated that this fall of erythrocyte 2,3-DPG was not due to a direct effect of fructose on the intra-erythrocytic regulation of 2,3-DPG or to changes indirectly related to the intravenous administration of fructose in vivo, i.e. an increase of the blood lactate/pyruvate ratio or a decrease of plasma inorganic phosphate. It is suggested that two opposing effects on the oxygen transport system of blood are induced by fructose infusions: 1) a displacement of the oxygen dissociation curve to the right due to the Bohr effect 2) a virtually counterbalancing shift of the oxygen dissociation curve to the left due to decreased erythrocyte 2,3-DPG concentrations."}
{"id": "PMID:4332", "title": "A comparison between a melanocyte-stimulating hormone inhibitory factor (MIF-I) and substances known to activate central dopamine receptors.", "content": "The tripeptide, prolyl-leucyl glycine amide, a melanocyte-stimulating hormone inhibitory factor (MIF-I), which has been reported to be effective in improving symptoms of Parkinson's disease, has been compared with drugs known to activate dopamine receptors in rat and mouse brain. Unlike apomorphine, amphetamine and amantadine it was incapable of producing sterotyped behaviour in the rat and unlike 1-dopa it was also ineffective in rats pretreated with the monoamineoxidase inhibitor mebanazine. Neither did it potentiate apomorphine nor amphetamine in this test. MIF-I did not antagonise chlorpromazine-induced loss of locomotor activity in mice, an effect which was antagonised by apomorphine, amphetamine and amantadine. Chlorpromazine hypothermia in the mouse was antagonised by 1-dopa but not by MIF-I; similar findings were obtained in reserpine-pretreated mice. These results suggest that the reported beneficial effect of MIF-I in Parkinson's disease is unlikely to be due to an interaction with dopamine systems in the brain.", "contents": "A comparison between a melanocyte-stimulating hormone inhibitory factor (MIF-I) and substances known to activate central dopamine receptors. The tripeptide, prolyl-leucyl glycine amide, a melanocyte-stimulating hormone inhibitory factor (MIF-I), which has been reported to be effective in improving symptoms of Parkinson's disease, has been compared with drugs known to activate dopamine receptors in rat and mouse brain. Unlike apomorphine, amphetamine and amantadine it was incapable of producing sterotyped behaviour in the rat and unlike 1-dopa it was also ineffective in rats pretreated with the monoamineoxidase inhibitor mebanazine. Neither did it potentiate apomorphine nor amphetamine in this test. MIF-I did not antagonise chlorpromazine-induced loss of locomotor activity in mice, an effect which was antagonised by apomorphine, amphetamine and amantadine. Chlorpromazine hypothermia in the mouse was antagonised by 1-dopa but not by MIF-I; similar findings were obtained in reserpine-pretreated mice. These results suggest that the reported beneficial effect of MIF-I in Parkinson's disease is unlikely to be due to an interaction with dopamine systems in the brain."}
{"id": "PMID:4334", "title": "Acute graft-versus-host reaction in mice. 3. Organ distribution of injected 51 chromium labeled lymphocytes.", "content": "The distribution of labeled lymph node cells, causing an acute GvH reaction in lethally irradiated allogeneic recipients, was studied. Lymph node cells of C57BL mice were labeled with 51Cr and injected into lethally irradiated: a) C57BL mice, b) CBA mice, c) CBA mice sensitized to C57BL antigens prior to irradiation, d) CBA mice splenectomized before irradiation. Two more experimental situations were studied in which C57BL donors of lymph node cells were: e) presensitized to CBA antigens, or f) deprived of T-lymphocytes. The amount of radioactivity was determined in the whole body, blood, liver, spleen, subcutaneous lymph nodes, lungs, femora and kidneys of the irradiated recipient at regular intervals from the time of injection to the 120th hour after it. We found that living cells lodged predominantly in the spleen and the lymph nodes, while dead and dying cells accumulated in the liver. Other organs contained very small amounts of radioactivity. All the results point to the primary role of the spleen in the acute graft-versus-host reaction.", "contents": "Acute graft-versus-host reaction in mice. 3. Organ distribution of injected 51 chromium labeled lymphocytes. The distribution of labeled lymph node cells, causing an acute GvH reaction in lethally irradiated allogeneic recipients, was studied. Lymph node cells of C57BL mice were labeled with 51Cr and injected into lethally irradiated: a) C57BL mice, b) CBA mice, c) CBA mice sensitized to C57BL antigens prior to irradiation, d) CBA mice splenectomized before irradiation. Two more experimental situations were studied in which C57BL donors of lymph node cells were: e) presensitized to CBA antigens, or f) deprived of T-lymphocytes. The amount of radioactivity was determined in the whole body, blood, liver, spleen, subcutaneous lymph nodes, lungs, femora and kidneys of the irradiated recipient at regular intervals from the time of injection to the 120th hour after it. We found that living cells lodged predominantly in the spleen and the lymph nodes, while dead and dying cells accumulated in the liver. Other organs contained very small amounts of radioactivity. All the results point to the primary role of the spleen in the acute graft-versus-host reaction."}
{"id": "PMID:4335", "title": "Mitigation of graft-versus-host disease in mice by treatment of donors with bacterial endotoxin.", "content": "Treatment of DBA/2 (H-2d) mice with bacterial endotoxin prior to transplantation of their spleen and lymph node cells into immunosuppressed AKR (H-2k) mice prevented acute mortality from graft-versus-host (GVH) disease. AKR mice that received immunocompetent cells from untreated DBA/2 mice had a median survival time (MST) of 13 days. In contrast, AKR mice that received immunocompetent cells from endotoxin-treated DBA/2 donors had an MST of 54 days. Endotoxin treatment of AKR recipients was not essential for preventing mortality from acute GVH disease. Chimerism was proved by demonstrating that the lymphoid cells of long-term surviving AKR mice had the characteristics of DBA/2 lymphoid cells as measured by their response in mixed leukocyte culture (MLC) tests. Spleen cells from endotoxin-treated DBA/2 mice were able to stimulate, and to be stimulated by, AKR spleen cells in MLC assays. Furthermore, spleen cells from endotoxin-treated DBA/2 mice did not suppress the responses of DBA/2 or AKR spleen cells in 'three-party' MLC tests.", "contents": "Mitigation of graft-versus-host disease in mice by treatment of donors with bacterial endotoxin. Treatment of DBA/2 (H-2d) mice with bacterial endotoxin prior to transplantation of their spleen and lymph node cells into immunosuppressed AKR (H-2k) mice prevented acute mortality from graft-versus-host (GVH) disease. AKR mice that received immunocompetent cells from untreated DBA/2 mice had a median survival time (MST) of 13 days. In contrast, AKR mice that received immunocompetent cells from endotoxin-treated DBA/2 donors had an MST of 54 days. Endotoxin treatment of AKR recipients was not essential for preventing mortality from acute GVH disease. Chimerism was proved by demonstrating that the lymphoid cells of long-term surviving AKR mice had the characteristics of DBA/2 lymphoid cells as measured by their response in mixed leukocyte culture (MLC) tests. Spleen cells from endotoxin-treated DBA/2 mice were able to stimulate, and to be stimulated by, AKR spleen cells in MLC assays. Furthermore, spleen cells from endotoxin-treated DBA/2 mice did not suppress the responses of DBA/2 or AKR spleen cells in 'three-party' MLC tests."}
{"id": "PMID:4341", "title": "Influence of diurnal cycles on biochemical parameters of drug sensitivity: the pineal gland as a model.", "content": "Diurnal cycles in physical parameters in the environment modulate biochemical and physiological circadian rhythms in experimental animals, including cycles in the sensitivity to external influences. Environmental lighting synchronizes cycles of indole metabolism and melatonin synthesis in the rat pineal gland by modulating the activity of postganglionic sympathetic nerves. As a consequence, the sensitivity of pineal N-acetyltransferase to stimulation by isoproterenol or by dibutyryl cyclic AMP varies diurnally. Also, the capacity of actinomycin D to inhibit this induction varies with circadian periodicity. The cycles in sensitivity to isoproterenol reflect cycles in the system that regulates cyclic AMP production, and include variation in the availability of specific B-adrenergic binding sites, and in the sensitivity of receptor-coupled adenylate cyclase to catecholamines. Further, a variation in the response to dibutyryl cyclic AMP indicates in addition the participation of intracellular controls in the regulation of the sensitivity of N-acetyltransferase to catecholamines. The varying sensitivity to actinomycin D suggests a changing requirement for the synthesis of RNA as a function of prior environmental lighting conditions. The basic nature of these sensitivity changes suggests that diurnal cycles of environmental lighting may similarly affect other systems.", "contents": "Influence of diurnal cycles on biochemical parameters of drug sensitivity: the pineal gland as a model. Diurnal cycles in physical parameters in the environment modulate biochemical and physiological circadian rhythms in experimental animals, including cycles in the sensitivity to external influences. Environmental lighting synchronizes cycles of indole metabolism and melatonin synthesis in the rat pineal gland by modulating the activity of postganglionic sympathetic nerves. As a consequence, the sensitivity of pineal N-acetyltransferase to stimulation by isoproterenol or by dibutyryl cyclic AMP varies diurnally. Also, the capacity of actinomycin D to inhibit this induction varies with circadian periodicity. The cycles in sensitivity to isoproterenol reflect cycles in the system that regulates cyclic AMP production, and include variation in the availability of specific B-adrenergic binding sites, and in the sensitivity of receptor-coupled adenylate cyclase to catecholamines. Further, a variation in the response to dibutyryl cyclic AMP indicates in addition the participation of intracellular controls in the regulation of the sensitivity of N-acetyltransferase to catecholamines. The varying sensitivity to actinomycin D suggests a changing requirement for the synthesis of RNA as a function of prior environmental lighting conditions. The basic nature of these sensitivity changes suggests that diurnal cycles of environmental lighting may similarly affect other systems."}
{"id": "PMID:4342", "title": "Nitrite, nitrosamines, and cancer.", "content": "Carcinogenic N-nitroso compounds are formed from the reaction of naturally-occurring amines and nitrites that may be added to foods or produced by bacterial reduction of nitrate. N-Nitroso compounds can be produced during processing, storage and preparation of foods and in the mammalian stomach. Factors that influence the rates of nitrosation reactions include pH, temperature, catalysts, and inhibitors. Predictions of the extent of nitrosation are complicated by these factors and ultimately the amounts and types of N-nitroso compounds present must be determined by direct analysis. Methods for detection and estimation of volatile nitrosamines are available and low levels (parts per billion) have been found in some cured meat and fish products. General methods for detection of all N-nitroso compounds are not available yet, but are under development. Evaluation of the risk to human populations from these compounds is difficult in the absence of more comprehensive data on their environmental distribution.", "contents": "Nitrite, nitrosamines, and cancer. Carcinogenic N-nitroso compounds are formed from the reaction of naturally-occurring amines and nitrites that may be added to foods or produced by bacterial reduction of nitrate. N-Nitroso compounds can be produced during processing, storage and preparation of foods and in the mammalian stomach. Factors that influence the rates of nitrosation reactions include pH, temperature, catalysts, and inhibitors. Predictions of the extent of nitrosation are complicated by these factors and ultimately the amounts and types of N-nitroso compounds present must be determined by direct analysis. Methods for detection and estimation of volatile nitrosamines are available and low levels (parts per billion) have been found in some cured meat and fish products. General methods for detection of all N-nitroso compounds are not available yet, but are under development. Evaluation of the risk to human populations from these compounds is difficult in the absence of more comprehensive data on their environmental distribution."}
{"id": "PMID:4345", "title": "Hypothalamic inactivation of thyrotrophin-releasing hormone.", "content": "Following the demonstration of peptidases in the rat hypothalamus which inactivate thyrotrophin-releasing hormone (TRH), a sensitive and specific radioimmunoassay for the releasing hormone was used to investigate the presence of similar peptidases in the rabbit hypothalamus. TRH was found to be rapidly inactivated by supernatant and particulate hypothalamic fractions, with higher peptidase activity in the supernatant than in the particulate fraction. An optimum pH of 7.3 within physiological limits was obtained for the enzymes in both the fractions examined. The results obtained confirm that the rabbit hypothalamus contains enzymes capable of inactivating TRH, and since it has been found that such peptidases interfere with studies on TRH biosynthesis, it is possible that the peptidases may play a part in controlling the releasing hormone's production. The specificity of the antiserum used in the radioimmunoassay has also suggested that the peptidases may cleave the C-terminal-ProNH2,-NH2 or both from the TRH molecule to cause inactivation.", "contents": "Hypothalamic inactivation of thyrotrophin-releasing hormone. Following the demonstration of peptidases in the rat hypothalamus which inactivate thyrotrophin-releasing hormone (TRH), a sensitive and specific radioimmunoassay for the releasing hormone was used to investigate the presence of similar peptidases in the rabbit hypothalamus. TRH was found to be rapidly inactivated by supernatant and particulate hypothalamic fractions, with higher peptidase activity in the supernatant than in the particulate fraction. An optimum pH of 7.3 within physiological limits was obtained for the enzymes in both the fractions examined. The results obtained confirm that the rabbit hypothalamus contains enzymes capable of inactivating TRH, and since it has been found that such peptidases interfere with studies on TRH biosynthesis, it is possible that the peptidases may play a part in controlling the releasing hormone's production. The specificity of the antiserum used in the radioimmunoassay has also suggested that the peptidases may cleave the C-terminal-ProNH2,-NH2 or both from the TRH molecule to cause inactivation."}
{"id": "PMID:4361", "title": "Effect of cimetidine on 24-hour intragastric acidity in normal subjects.", "content": "The effect of H2-receptor blockade on intragastric acidity was studied in nine normal males. The pH of their gastric contents was measured at hourly daytime and two hourly nighttime intervals for 48 hours. The subjects ate identical meals, drank identical volumes of fluid, and smoked the same number of cigarettes during the two study days. Their physical activity was unrestricted in a ward environment. Blood cimetidine and plasma gastrin were measured in serial blood samples. The nine subjects were treated in random sequence with cimetidine 0-8-1-0 g on one day and placebo capsules on the other. The drug was given in four divided doses: four subjects received it before, and five after, the three main meals. All took the fourth dose at bedtime. Replicate studies in an additional subject given placebo on both study days showed good reproducibility (r=0-80, P less than 0-01). Cimetidine therapy decreased intragastric acidity in all nine subjects. The decrease was similar in the two groups taking the drug before or after meals, mean 24 h intragastric hydrogen ion activity being lowered by 70 and 72% respectively. Nocturnal anacidity was recorded in only two of 45 samples. Administration of cimetidine before meals produced earlier and higher drug blood levels than post-prandial medication, but when it was taken after food the blood levels were highest at the time when the buffer capacity of the food was waning. Blood concentrations of cimetidine exceeded the secretory IC50 level for most of the time between doses. The results show that cimetidine 0-8-1-0 g/day in four divided doses produces a striking and consistent decrease of intragastric acidity. Although variation in the timing of the dose in relation to meals did not affect the decrease of acidity, the absorption data suggest that patients should take the drug after meals.", "contents": "Effect of cimetidine on 24-hour intragastric acidity in normal subjects. The effect of H2-receptor blockade on intragastric acidity was studied in nine normal males. The pH of their gastric contents was measured at hourly daytime and two hourly nighttime intervals for 48 hours. The subjects ate identical meals, drank identical volumes of fluid, and smoked the same number of cigarettes during the two study days. Their physical activity was unrestricted in a ward environment. Blood cimetidine and plasma gastrin were measured in serial blood samples. The nine subjects were treated in random sequence with cimetidine 0-8-1-0 g on one day and placebo capsules on the other. The drug was given in four divided doses: four subjects received it before, and five after, the three main meals. All took the fourth dose at bedtime. Replicate studies in an additional subject given placebo on both study days showed good reproducibility (r=0-80, P less than 0-01). Cimetidine therapy decreased intragastric acidity in all nine subjects. The decrease was similar in the two groups taking the drug before or after meals, mean 24 h intragastric hydrogen ion activity being lowered by 70 and 72% respectively. Nocturnal anacidity was recorded in only two of 45 samples. Administration of cimetidine before meals produced earlier and higher drug blood levels than post-prandial medication, but when it was taken after food the blood levels were highest at the time when the buffer capacity of the food was waning. Blood concentrations of cimetidine exceeded the secretory IC50 level for most of the time between doses. The results show that cimetidine 0-8-1-0 g/day in four divided doses produces a striking and consistent decrease of intragastric acidity. Although variation in the timing of the dose in relation to meals did not affect the decrease of acidity, the absorption data suggest that patients should take the drug after meals."}
{"id": "PMID:4366", "title": "The effects of some factors on the growth and morphology of Naegleria sp. and three strains of the genus Acanthamoeba.", "content": "The effects of various biophysical and chemical factors on the cytology of vegetative stages of Naegleria sp., Vitek strain, Acanthamoeba culbertsoni, Acanthamoeba castellanii, Neff strain and Acanthamoeba polyphaga, No. 1289, were studied. The amoebae were cultured in a liquid medium under axenic conditions. The optimum temperature was 37 degrees C for pathogenic strains of Naegleria sp. and Acanthamoeba culbertsoni and 20 degrees C for A. castellanii. No changes were observed in the growth of A. polyphaga at the temperatures 20 degrees and 37 degrees C. The strains investigated grew at pH values of 5.6 to 7.7 using Soerensen's buffer. At the limit values the growth was inhibited and the morphology of cells was markedly changed. All of the four strains grew still at pH 8.4 kept by NaHCO3. A. polyphaga grew at partial anaerobiosis. The three tested strains of the genus Acanthamoeba grew in liquid axenic medium with 0.89% NaCl. The growth of Naegleria sp., Vitek was inhibited already at 0.2% concentration of this salt. The addition of 3 X 10(-2) m KCl to the culture medium had a harmful effect on the growth and morphology of three tested strains, except A. polyphaga. In the culture medium containing 2 X 10(-3) m CaCl2 the encystment of both pathogenic strains was stimulated. The cytological changes under experimental conditions were manifested by atypical movement of trophozoits and their intracellular structure.", "contents": "The effects of some factors on the growth and morphology of Naegleria sp. and three strains of the genus Acanthamoeba. The effects of various biophysical and chemical factors on the cytology of vegetative stages of Naegleria sp., Vitek strain, Acanthamoeba culbertsoni, Acanthamoeba castellanii, Neff strain and Acanthamoeba polyphaga, No. 1289, were studied. The amoebae were cultured in a liquid medium under axenic conditions. The optimum temperature was 37 degrees C for pathogenic strains of Naegleria sp. and Acanthamoeba culbertsoni and 20 degrees C for A. castellanii. No changes were observed in the growth of A. polyphaga at the temperatures 20 degrees and 37 degrees C. The strains investigated grew at pH values of 5.6 to 7.7 using Soerensen's buffer. At the limit values the growth was inhibited and the morphology of cells was markedly changed. All of the four strains grew still at pH 8.4 kept by NaHCO3. A. polyphaga grew at partial anaerobiosis. The three tested strains of the genus Acanthamoeba grew in liquid axenic medium with 0.89% NaCl. The growth of Naegleria sp., Vitek was inhibited already at 0.2% concentration of this salt. The addition of 3 X 10(-2) m KCl to the culture medium had a harmful effect on the growth and morphology of three tested strains, except A. polyphaga. In the culture medium containing 2 X 10(-3) m CaCl2 the encystment of both pathogenic strains was stimulated. The cytological changes under experimental conditions were manifested by atypical movement of trophozoits and their intracellular structure."}
{"id": "PMID:4369", "title": "[Potassium substitutes during tocolysis].", "content": "The level of serum potassium during tokolytic therapy with Partusisten and Isoptin decreases in the first 24 hours of therapy. This decrease is not due to an increase in renal potassium elimination. During tokolytic treatment the serum level of potassium returns to its normal value after 48 hours without potassium substitution. While there is a decrease in serum potassium noticeable changes in electrocardiogram which are typial for hypopotassemia are observed. These changes disappear afer 48 hours of tokolytic treatment but never the less the initial serum potassium drop should be balanced by potassium substitution within these 48 hours.", "contents": "[Potassium substitutes during tocolysis]. The level of serum potassium during tokolytic therapy with Partusisten and Isoptin decreases in the first 24 hours of therapy. This decrease is not due to an increase in renal potassium elimination. During tokolytic treatment the serum level of potassium returns to its normal value after 48 hours without potassium substitution. While there is a decrease in serum potassium noticeable changes in electrocardiogram which are typial for hypopotassemia are observed. These changes disappear afer 48 hours of tokolytic treatment but never the less the initial serum potassium drop should be balanced by potassium substitution within these 48 hours."}
{"id": "PMID:4370", "title": "[Ambulatory therapy of trichomoniasis vaginalis. Clinical trial of a new Trichomonas-active azide substance].", "content": "Report on the results of the clinical trial of a new trichomonacide in ambulatory patients in a gynaecological practice. A report is given on a new drug for the treatment of vaginal trichomoniasis, which has been tried in 87 patients of a gynaecological practice under outpatient conditions. The rate of failures was 5.7% (5 of 87 cases). The advantages over alternative preparations is to be seen in the short duration of treatment (24 hours at the most), and in the favourable tolerance in spite of high doses.", "contents": "[Ambulatory therapy of trichomoniasis vaginalis. Clinical trial of a new Trichomonas-active azide substance]. Report on the results of the clinical trial of a new trichomonacide in ambulatory patients in a gynaecological practice. A report is given on a new drug for the treatment of vaginal trichomoniasis, which has been tried in 87 patients of a gynaecological practice under outpatient conditions. The rate of failures was 5.7% (5 of 87 cases). The advantages over alternative preparations is to be seen in the short duration of treatment (24 hours at the most), and in the favourable tolerance in spite of high doses."}
{"id": "PMID:4375", "title": "Purification and properties of Klebsiella pneumoniae heat-stable enterotoxin.", "content": "The enterotoxic material in cell-free growth preparations of Klebsiella pneumoniae serotype 5 was purified by sequential ultrafiltration and gel filtration (GF) procedures and the fractions were assayed for enterotoxic activity by determining their ability to induce in vivo net water secretion in the rat jejunum. Whole-cell lysates were inactive. Anaerobic broth culture conditions yielded a 10-fold increase in toxin production over aerobic conditions. Enterotoxic activity was absent in the UM-10 retentate of the broth filtrate but present in both the retentate and filtrate of the UM-2 membrane. GF of the two UM-2 ultrafiltration fractions through a Sephadex G-25 column yielded an active eluate, whose potency was increased by 10- or 200-fold, in or adjacent to the void volume. When subsequently passed through a G-50 column, these pools eluted at a Kav of between 0.4 and 0.6 and were further increased in potency by two- or fivefold. A second equally potent fraction was also recovered in the void volume of the G-50 eluate of the UM-2 filtrate; this may represent a polymer. Progressive purification by GF was associated with an increased protein and decreased carbohydrate content of the most active fractions. The most active G-50 eluate of the UM-2 retentate had a minimal effective enterotoxic dose of 5 mug/ml and that of the filtrate was less than 0.1 mug/ml. Heating the active GF eluates to 100 C for 30 min did not abolish enterotoxic activity and lowering the pH to 1 or incubation with either Pronase or trypsin had no effect on activity. These observations indicate that K. pneumoniae heat-stable enterotoxin is probably a single toxin with an apparent molecular weight in the range of 5,000. The elution characteristics during GF as well as the chemical composition of the most purified enterotoxin fractions indicate that the toxin is not associated with endotoxin.", "contents": "Purification and properties of Klebsiella pneumoniae heat-stable enterotoxin. The enterotoxic material in cell-free growth preparations of Klebsiella pneumoniae serotype 5 was purified by sequential ultrafiltration and gel filtration (GF) procedures and the fractions were assayed for enterotoxic activity by determining their ability to induce in vivo net water secretion in the rat jejunum. Whole-cell lysates were inactive. Anaerobic broth culture conditions yielded a 10-fold increase in toxin production over aerobic conditions. Enterotoxic activity was absent in the UM-10 retentate of the broth filtrate but present in both the retentate and filtrate of the UM-2 membrane. GF of the two UM-2 ultrafiltration fractions through a Sephadex G-25 column yielded an active eluate, whose potency was increased by 10- or 200-fold, in or adjacent to the void volume. When subsequently passed through a G-50 column, these pools eluted at a Kav of between 0.4 and 0.6 and were further increased in potency by two- or fivefold. A second equally potent fraction was also recovered in the void volume of the G-50 eluate of the UM-2 filtrate; this may represent a polymer. Progressive purification by GF was associated with an increased protein and decreased carbohydrate content of the most active fractions. The most active G-50 eluate of the UM-2 retentate had a minimal effective enterotoxic dose of 5 mug/ml and that of the filtrate was less than 0.1 mug/ml. Heating the active GF eluates to 100 C for 30 min did not abolish enterotoxic activity and lowering the pH to 1 or incubation with either Pronase or trypsin had no effect on activity. These observations indicate that K. pneumoniae heat-stable enterotoxin is probably a single toxin with an apparent molecular weight in the range of 5,000. The elution characteristics during GF as well as the chemical composition of the most purified enterotoxin fractions indicate that the toxin is not associated with endotoxin."}
{"id": "PMID:4376", "title": "Activity of two Streptococcus mutans bacteriocins in the presence of saliva, levan, and dextran.", "content": "The extracellular dextrans produced from sucrose by Streptococcus mutans strains BHT and GS-5 did not prevent the synthesis or release of active bacteriocins by these two strains. In addition, several streptococci that were genetically sensitive to these bacteriocins, and that could synthesize a variety of extracellular dextrans and levans from sucrose, remained phenotypically sensitive when grown in the presence of sucrose. Bacteriocin activity was not altered by treatment with high-molecular-weight dextran or by human saliva. The bacteriocins produced by, and active against, S. mutans thus appear to be capable of acting in vivo and may play a role in regulating the bacterial ecology of the oral cavity.", "contents": "Activity of two Streptococcus mutans bacteriocins in the presence of saliva, levan, and dextran. The extracellular dextrans produced from sucrose by Streptococcus mutans strains BHT and GS-5 did not prevent the synthesis or release of active bacteriocins by these two strains. In addition, several streptococci that were genetically sensitive to these bacteriocins, and that could synthesize a variety of extracellular dextrans and levans from sucrose, remained phenotypically sensitive when grown in the presence of sucrose. Bacteriocin activity was not altered by treatment with high-molecular-weight dextran or by human saliva. The bacteriocins produced by, and active against, S. mutans thus appear to be capable of acting in vivo and may play a role in regulating the bacterial ecology of the oral cavity."}
{"id": "PMID:4377", "title": "Cephacetrile, a new cephalosporin: in vitro, pharmacological and clinical evaluation.", "content": "Cephacetrile, a parenteral cephalosporin, was evaluated for in vitro antibacterial activity, clinical pharmacology and effectiveness in the treatment of severe infections. The antibacterial activity against 187 isolates was determined by an agar-dilution technique. The MICs were 0.06 to 0.5 mug/ml for Group A Streptococcus, D. pneumoniae, and Staph. aureus, 4-6 mug/ml for E. coli and Klebsiella-Enterobacter 8-32 mug/ml for Pr. mirabilis and more than 500 mug/ml for Ps. aeruginosa. A few strains of Klebsiella and E. coli had MICs of more than 125 mcg/ml. Serum levels after 0.5 and 1 g of i.m. cephacetrile were respectively 14.6 and 18.6 mug/ml after 1 hr, and 1.5 and 2.5 mug/ml after 6 hr. Serum levels after i.v. infusion of 0.5 and 1 g were respectively 16 and 25 mug/ml after 1 hr., and 1 and 2 mug/ml after 6 hr. Urine levels after 0.5 and 1 g i.m. cephacetrile were respectively 500 and 650 mug/ml in the 0-3 hr period, and 250 and 300 mug/ml in the 3-6 hr period. Renal clearance was 166 +/- 5 ml/min/1.73 m2; renal excretion was about 20% of the dose 6 hr after i.m. injection. Cephacetrile was well tolerated when administered i.m. with lidocaine. Mild phlebitis occurred sometimes after i.v. infusions. The clinical response, evaluated in 36 patients with severe systemic, respiratory and urinary infections, was good in all but two cases.", "contents": "Cephacetrile, a new cephalosporin: in vitro, pharmacological and clinical evaluation. Cephacetrile, a parenteral cephalosporin, was evaluated for in vitro antibacterial activity, clinical pharmacology and effectiveness in the treatment of severe infections. The antibacterial activity against 187 isolates was determined by an agar-dilution technique. The MICs were 0.06 to 0.5 mug/ml for Group A Streptococcus, D. pneumoniae, and Staph. aureus, 4-6 mug/ml for E. coli and Klebsiella-Enterobacter 8-32 mug/ml for Pr. mirabilis and more than 500 mug/ml for Ps. aeruginosa. A few strains of Klebsiella and E. coli had MICs of more than 125 mcg/ml. Serum levels after 0.5 and 1 g of i.m. cephacetrile were respectively 14.6 and 18.6 mug/ml after 1 hr, and 1.5 and 2.5 mug/ml after 6 hr. Serum levels after i.v. infusion of 0.5 and 1 g were respectively 16 and 25 mug/ml after 1 hr., and 1 and 2 mug/ml after 6 hr. Urine levels after 0.5 and 1 g i.m. cephacetrile were respectively 500 and 650 mug/ml in the 0-3 hr period, and 250 and 300 mug/ml in the 3-6 hr period. Renal clearance was 166 +/- 5 ml/min/1.73 m2; renal excretion was about 20% of the dose 6 hr after i.m. injection. Cephacetrile was well tolerated when administered i.m. with lidocaine. Mild phlebitis occurred sometimes after i.v. infusions. The clinical response, evaluated in 36 patients with severe systemic, respiratory and urinary infections, was good in all but two cases."}
{"id": "PMID:4378", "title": "Pituitary gonadotropin response to luteinizing hormone-releasing hormone (LH-RH) in males with azo- and oligospermia.", "content": "Twenty-one males with azo- or oligospermia presenting with infertility and with no evidence of organic disease were studied with luteinizing hormone - releasing hormone (LH-RH). A pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) response was present in all cases and was normal in the majority of the subjects. Serum testosterone and 17 beta estradiol levels were normal in all cases studied. No significant correlations were found between the gonadotropin estimations and sperm count, basal serum testosterone or testosterone response to human chorionic gonadotropin. It is concluded that LH-RH is of limited diagnostic use in the investigation of this group of patients with male infertility and provides no further insight into the pathogenesis of this condition.", "contents": "Pituitary gonadotropin response to luteinizing hormone-releasing hormone (LH-RH) in males with azo- and oligospermia. Twenty-one males with azo- or oligospermia presenting with infertility and with no evidence of organic disease were studied with luteinizing hormone - releasing hormone (LH-RH). A pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) response was present in all cases and was normal in the majority of the subjects. Serum testosterone and 17 beta estradiol levels were normal in all cases studied. No significant correlations were found between the gonadotropin estimations and sperm count, basal serum testosterone or testosterone response to human chorionic gonadotropin. It is concluded that LH-RH is of limited diagnostic use in the investigation of this group of patients with male infertility and provides no further insight into the pathogenesis of this condition."}
{"id": "PMID:4380", "title": "Age at the menopause and onset of the climacteric in women of Martin District, Czechoslovkia. Statistical survey and some biological and social correlations.", "content": "In this study, 6877 women were analysed whose ages ranged between 38 and 58 (born between 1909 and 1929) and who had had no artificial menopause. This is 88.04% of the total female population in this actual period of life, living in Martin District in 1967. The mean age at the menopause was found, by status quo method, to be 51.21 years (standard deviation 4.4), and by the method of weighted arithmetical means, 48.81 years, (standard deviation 3.9). The mean age at the onset of the climacteric, calculated by the same methods, was 47.55 years, or 46.74 years, respectively. The mean age at menarche was 14.6 years. The average birth-rate was 2.8. The mean period of fertility for the series as a whole was 36.6 years. Women with menstrual disturbances had their menopause about 1 year earlier. We have noted a similar tendency in nulliparas and primiparas. We could find no great difference in the age at menopause between those who had had an early or a late menarche. Menstrual disturbances also influenced the onset of the climacteric. It was at least one year earlier than with regular menstruation. Age at menarche and parity had no effect on the age at the onset of climacteric. Women working in agriculture and housewives had their menopause a little later than mean age of the series, whereas manual workers and those in other occupational categories had their menopause and onset of the climacteric about 1 year earlier. Furthermore, single women had their menopause about one year earlier than the married ones. Widows had their menopause twice so often as the married women and they got it very soon after the husbands's death.", "contents": "Age at the menopause and onset of the climacteric in women of Martin District, Czechoslovkia. Statistical survey and some biological and social correlations. In this study, 6877 women were analysed whose ages ranged between 38 and 58 (born between 1909 and 1929) and who had had no artificial menopause. This is 88.04% of the total female population in this actual period of life, living in Martin District in 1967. The mean age at the menopause was found, by status quo method, to be 51.21 years (standard deviation 4.4), and by the method of weighted arithmetical means, 48.81 years, (standard deviation 3.9). The mean age at the onset of the climacteric, calculated by the same methods, was 47.55 years, or 46.74 years, respectively. The mean age at menarche was 14.6 years. The average birth-rate was 2.8. The mean period of fertility for the series as a whole was 36.6 years. Women with menstrual disturbances had their menopause about 1 year earlier. We have noted a similar tendency in nulliparas and primiparas. We could find no great difference in the age at menopause between those who had had an early or a late menarche. Menstrual disturbances also influenced the onset of the climacteric. It was at least one year earlier than with regular menstruation. Age at menarche and parity had no effect on the age at the onset of climacteric. Women working in agriculture and housewives had their menopause a little later than mean age of the series, whereas manual workers and those in other occupational categories had their menopause and onset of the climacteric about 1 year earlier. Furthermore, single women had their menopause about one year earlier than the married ones. Widows had their menopause twice so often as the married women and they got it very soon after the husbands's death."}
{"id": "PMID:4381", "title": "Fibrinolytic activity of the rat ovum, appearance during tubal passage and disappearance at implantation.", "content": "Fertilized rat ova were histochemically examined for their fibrinolytic activity. Activity was found during tubal passage, which disappeared at implantation. Simultaneously the fibrinolytic activity of the endometrium disappeared at deciduation. These changes might be a prerequisite for implantation of the zygote.", "contents": "Fibrinolytic activity of the rat ovum, appearance during tubal passage and disappearance at implantation. Fertilized rat ova were histochemically examined for their fibrinolytic activity. Activity was found during tubal passage, which disappeared at implantation. Simultaneously the fibrinolytic activity of the endometrium disappeared at deciduation. These changes might be a prerequisite for implantation of the zygote."}
{"id": "PMID:4382", "title": "Juvenile diabetes and human sperm quality.", "content": "Spermiological findings in 25 juvenile diabetics in the age range 16 to 22 years (average 18.5) have been compared with normal spermiological findings in 24 individuals of the same age (16 to 22 years, average 18.7). A drift to lower sperm values in the group of the juvenile diabetics became evident in all parameters observed. As concerns motility and morphology, the differences between the groups reached statistically significant values.", "contents": "Juvenile diabetes and human sperm quality. Spermiological findings in 25 juvenile diabetics in the age range 16 to 22 years (average 18.5) have been compared with normal spermiological findings in 24 individuals of the same age (16 to 22 years, average 18.7). A drift to lower sperm values in the group of the juvenile diabetics became evident in all parameters observed. As concerns motility and morphology, the differences between the groups reached statistically significant values."}
{"id": "PMID:4383", "title": "On round-headed human spermatozoa.", "content": "In an infertile man and his only, likewise infertile, brother the sperm contained only round-headed spermatozoa. Electron microscopic examination of embedded ejaculate revealed a malformation, viz. absence of acrosomes in all the spermatozoa with consequent lack of normal development of the heads of the spermatozoa. Acrosomeless spermatozoa were also found in the testicular tubuli. No disturbance of the endocrine functions could be demonstrated. The blood cells were of normal male karyotype. Investigation of meiosis, on the other hand, showed rudimentary second division. Two other unrelated infertile men showed the same isolated disturbance in their spermiogram. Treatment with chlomiphene had no effect on the structure of the spermatozoa or on the infertility. The rare disorder, which seems to be a special syndrome, the first hitherto distinguishable among the various types of teratospermia, and its probable background are discussed.", "contents": "On round-headed human spermatozoa. In an infertile man and his only, likewise infertile, brother the sperm contained only round-headed spermatozoa. Electron microscopic examination of embedded ejaculate revealed a malformation, viz. absence of acrosomes in all the spermatozoa with consequent lack of normal development of the heads of the spermatozoa. Acrosomeless spermatozoa were also found in the testicular tubuli. No disturbance of the endocrine functions could be demonstrated. The blood cells were of normal male karyotype. Investigation of meiosis, on the other hand, showed rudimentary second division. Two other unrelated infertile men showed the same isolated disturbance in their spermiogram. Treatment with chlomiphene had no effect on the structure of the spermatozoa or on the infertility. The rare disorder, which seems to be a special syndrome, the first hitherto distinguishable among the various types of teratospermia, and its probable background are discussed."}
{"id": "PMID:4384", "title": "Assessment of the therapeutic effect of epimestrol and epimestrol associated with clomiphene in female sterility.", "content": "In 24 women with disturbances of ovulation treated for sterility with Epimestrol, ovulation was achieved in 3 patients but none of these became pregnant after therapy. Since it has been suggested that the association of Clomiphene with a weak estrogen might improve the pregnancy rate, we decided to administer Clomiphene associated with Epimestrol. Using this combined therapy in 58 patients, 32 out of the 58 women ovulated and 17 conceived. The overall rate of pregnancy using the combined therapy was no better than that obtained when Clomiphene alone is administered. From this study it is concluded that: (1) Epimestrol is not an effective method for the induction of ovulation, and (2) addition of Epimestrol to Clomiphene is of no clinical benefit.", "contents": "Assessment of the therapeutic effect of epimestrol and epimestrol associated with clomiphene in female sterility. In 24 women with disturbances of ovulation treated for sterility with Epimestrol, ovulation was achieved in 3 patients but none of these became pregnant after therapy. Since it has been suggested that the association of Clomiphene with a weak estrogen might improve the pregnancy rate, we decided to administer Clomiphene associated with Epimestrol. Using this combined therapy in 58 patients, 32 out of the 58 women ovulated and 17 conceived. The overall rate of pregnancy using the combined therapy was no better than that obtained when Clomiphene alone is administered. From this study it is concluded that: (1) Epimestrol is not an effective method for the induction of ovulation, and (2) addition of Epimestrol to Clomiphene is of no clinical benefit."}
{"id": "PMID:4385", "title": "Improvement of fertility and semen quality in men treated with a combination of anticongestive and antibiotic drugs.", "content": "The effects of a combined therapy of antibiotics and antiinflammatory drugs was evaluated in 344 men referred to our clinic for treatment of infertility. Physical signs of congestion, usually not severe, were detected in 244 men. The treatment caused significant improvement in semen quality, especially in sperm concentration, morphology and motility. Forty percent of the wives became pregnant. There was a striking relationship between increase in morphologically normal spermatozoa and incidence of pregnancy. It is speculated that the therapy had its major effect at the level of the epididymis and/or testis.", "contents": "Improvement of fertility and semen quality in men treated with a combination of anticongestive and antibiotic drugs. The effects of a combined therapy of antibiotics and antiinflammatory drugs was evaluated in 344 men referred to our clinic for treatment of infertility. Physical signs of congestion, usually not severe, were detected in 244 men. The treatment caused significant improvement in semen quality, especially in sperm concentration, morphology and motility. Forty percent of the wives became pregnant. There was a striking relationship between increase in morphologically normal spermatozoa and incidence of pregnancy. It is speculated that the therapy had its major effect at the level of the epididymis and/or testis."}
{"id": "PMID:4386", "title": "Genital organs. Auto and homotransplantation in forty dogs.", "content": "Auto and homo transplantation of the uterus and ovaries was studied in 40 bitches divided into four groups. Group A served as a control. In group B the omentopexy technique of auto-transplantation was used. This method did not prove very rewarding and all 12 grafts were found to have degenerated and were non-functioning when relaparotomy was performed, 3 months after transplantation. In group C, auto transplantation with vascular anastomosis was performed in 12 dogs, yielding satisfactory results including one successful pregnancy and the delivery of 3 healthy puppies. In group D homotransplantation of the internal genital organs was performed in two sets of twin dogs. No immunosuppressive treatment was used. These grafts survived for a limited period as proved by the functional tests and X-ray examination but after 3 months were found to be necrotic and degenerated. Graft function and viability was established by: X-ray examination, cytology of vaginal smears, the effect of gonadotropins on the grafted ovaries and finally relaparotomy undertaken after 3 weeks and 3 months.", "contents": "Genital organs. Auto and homotransplantation in forty dogs. Auto and homo transplantation of the uterus and ovaries was studied in 40 bitches divided into four groups. Group A served as a control. In group B the omentopexy technique of auto-transplantation was used. This method did not prove very rewarding and all 12 grafts were found to have degenerated and were non-functioning when relaparotomy was performed, 3 months after transplantation. In group C, auto transplantation with vascular anastomosis was performed in 12 dogs, yielding satisfactory results including one successful pregnancy and the delivery of 3 healthy puppies. In group D homotransplantation of the internal genital organs was performed in two sets of twin dogs. No immunosuppressive treatment was used. These grafts survived for a limited period as proved by the functional tests and X-ray examination but after 3 months were found to be necrotic and degenerated. Graft function and viability was established by: X-ray examination, cytology of vaginal smears, the effect of gonadotropins on the grafted ovaries and finally relaparotomy undertaken after 3 weeks and 3 months."}
{"id": "PMID:4387", "title": "Crossed immunoelectrophoresis of sperm antibodies in human serum and cervical mucus.", "content": "Sperm agglutinating antibodies are purified from sera and cervical mucus of women with unexplained causes of infertility which were positive in the FD-test. Fractionation was performed by affinity-chromatography in a batch device and the sperm agglutinating activity controlled by the Franklin and Dukes test. This sperm antibody fraction was determined via crossed immunoelectrophoresis by migration into an anti-human serum containing gel. In all cases only one big peak resulted. The negative control serum and mucus samples demonstrated no precipitation peaks. By absorption studies it was shown that the sperm agglutinating antibodies in sera were IgM and in cervical mucus IgA. The concentration of IgA and IgM was determined by comparison with standard human IgA and IgM. Thus only one serum- and one cervical mucus antibody seems to be responsible for agglutination. The number of experiments, however, is still too small for general conclusions. This method is easily and quickly performed and can therefore be used as a routine method for the determination of sperm agglutinating antibodies. Its application for sperm-immobilizing or cytotoxic activity remains to be tested.", "contents": "Crossed immunoelectrophoresis of sperm antibodies in human serum and cervical mucus. Sperm agglutinating antibodies are purified from sera and cervical mucus of women with unexplained causes of infertility which were positive in the FD-test. Fractionation was performed by affinity-chromatography in a batch device and the sperm agglutinating activity controlled by the Franklin and Dukes test. This sperm antibody fraction was determined via crossed immunoelectrophoresis by migration into an anti-human serum containing gel. In all cases only one big peak resulted. The negative control serum and mucus samples demonstrated no precipitation peaks. By absorption studies it was shown that the sperm agglutinating antibodies in sera were IgM and in cervical mucus IgA. The concentration of IgA and IgM was determined by comparison with standard human IgA and IgM. Thus only one serum- and one cervical mucus antibody seems to be responsible for agglutination. The number of experiments, however, is still too small for general conclusions. This method is easily and quickly performed and can therefore be used as a routine method for the determination of sperm agglutinating antibodies. Its application for sperm-immobilizing or cytotoxic activity remains to be tested."}
{"id": "PMID:4388", "title": "Microbiopsy of the fallopian tube as a method for clinical investigation of tubal function in infertility.", "content": "Microbiopsy of the fimbrial end of the fallopian tube may prove to be a valuable method for investigating the tubal pick-up and transport mechanism in infertility patients. Counting of the percentage of ciliated cells on semithin sections shows that in normal fertile women a percentage of such cells is present that is higher than in abnormal conditions such as peritubal adhesions, ectopic pregnancy and amenorrhoea following prolonged progestogen treatment. It is also suggested that ultrastructural examination of the biopsy may provide additional valuable information.", "contents": "Microbiopsy of the fallopian tube as a method for clinical investigation of tubal function in infertility. Microbiopsy of the fimbrial end of the fallopian tube may prove to be a valuable method for investigating the tubal pick-up and transport mechanism in infertility patients. Counting of the percentage of ciliated cells on semithin sections shows that in normal fertile women a percentage of such cells is present that is higher than in abnormal conditions such as peritubal adhesions, ectopic pregnancy and amenorrhoea following prolonged progestogen treatment. It is also suggested that ultrastructural examination of the biopsy may provide additional valuable information."}
{"id": "PMID:4389", "title": "Improvement of sperm motility in patients with asthenozoospermia by kallikrein treatment.", "content": "Parenteral and oral application of kallikrein (EC 3.4.21.8)--a kinin-releasing proteinase from porcine pancreatic tissue--significantly stimulates quantitative and qualitative sperm motility in subfertile males with semen criteria of asthenozoospermia. Improvement of sperm motility was found to exist for at least 3 months following termination of the 7 week duration kallikrein treatment. Additionally, a significant increase in the number of spermatozoa was observed 3 and 5 months after starting parenteral application of kallikrein.", "contents": "Improvement of sperm motility in patients with asthenozoospermia by kallikrein treatment. Parenteral and oral application of kallikrein (EC 3.4.21.8)--a kinin-releasing proteinase from porcine pancreatic tissue--significantly stimulates quantitative and qualitative sperm motility in subfertile males with semen criteria of asthenozoospermia. Improvement of sperm motility was found to exist for at least 3 months following termination of the 7 week duration kallikrein treatment. Additionally, a significant increase in the number of spermatozoa was observed 3 and 5 months after starting parenteral application of kallikrein."}
{"id": "PMID:4390", "title": "Oligozoospermia: a seven-year survey of the incidence, chromosomal aberrations, treatment and pregnancy rate.", "content": "No sperm count should be regarded too low to consider extensive treatment in order to improve semen or to correct any possible abnormalities in femal partners. The infertile couple should be given devoted care and advice to improve their sexual relations and their psychological attitude towards the problem of infertility. A pregnancy rate of 51.9% where the husband's count was less than 10 million/ml, offers adequate support for this statement. In cases of mental trauma inflicted on patients by a verdict of inability to achieve parenthood--on people who have already suffered severe psychological shock and tension resulting from a period of infertility--discouragement lessens the already doubtful chances of achieving pregnancy. In no circumstance should oligozoospermic patients receive treatment for infertility unless a chromosomal analysis has been completed and found normal, since our rate of chromosomal anomalies (11.4%) in a group of oligozoospermic patients is considered to be too high.", "contents": "Oligozoospermia: a seven-year survey of the incidence, chromosomal aberrations, treatment and pregnancy rate. No sperm count should be regarded too low to consider extensive treatment in order to improve semen or to correct any possible abnormalities in femal partners. The infertile couple should be given devoted care and advice to improve their sexual relations and their psychological attitude towards the problem of infertility. A pregnancy rate of 51.9% where the husband's count was less than 10 million/ml, offers adequate support for this statement. In cases of mental trauma inflicted on patients by a verdict of inability to achieve parenthood--on people who have already suffered severe psychological shock and tension resulting from a period of infertility--discouragement lessens the already doubtful chances of achieving pregnancy. In no circumstance should oligozoospermic patients receive treatment for infertility unless a chromosomal analysis has been completed and found normal, since our rate of chromosomal anomalies (11.4%) in a group of oligozoospermic patients is considered to be too high."}
{"id": "PMID:4391", "title": "Further studies on the fertility promoting factor from human seminal plasma.", "content": "A small molecular weight substance from human seminal plasma has been further purified by chromatography. The fertility promoting action of this factor on epididymal sperm has been confirmed in mouse in vitro and in vivo. Experimental evidence indicates that the factor acts on the sperm and not on the eggs. Its possible mode of action is by improving the motility and survival of the epididymal sperm.", "contents": "Further studies on the fertility promoting factor from human seminal plasma. A small molecular weight substance from human seminal plasma has been further purified by chromatography. The fertility promoting action of this factor on epididymal sperm has been confirmed in mouse in vitro and in vivo. Experimental evidence indicates that the factor acts on the sperm and not on the eggs. Its possible mode of action is by improving the motility and survival of the epididymal sperm."}
{"id": "PMID:4392", "title": "The presence of paternal H-2 antigens on hybrid mouse blastocysts during experimental delay of implantation and the disappearance of these antigens after onset of implantation.", "content": "The presence of paternal H-2 antigens on hybrid mouse blastocysts before and during implantation was investigated by means of the isotope anti-globulin technique. It was found that experimentally delayed blastocysts possess paternal H-2 antigens whereas these antigens can no longer be detected 14 hours after estradiol activation of delayed blastocysts.", "contents": "The presence of paternal H-2 antigens on hybrid mouse blastocysts during experimental delay of implantation and the disappearance of these antigens after onset of implantation. The presence of paternal H-2 antigens on hybrid mouse blastocysts before and during implantation was investigated by means of the isotope anti-globulin technique. It was found that experimentally delayed blastocysts possess paternal H-2 antigens whereas these antigens can no longer be detected 14 hours after estradiol activation of delayed blastocysts."}
{"id": "PMID:4394", "title": "Effect of copper and plastic intra-uterine devices on the fibrinolytic activity of the endometrium in the rat.", "content": "The effect of copper and plastic intrauterine devices (IUD) on the fibrinolytic activity of the endometrium was studied in the rat. A copper or a plastic device was placed in one of the uterine horns, while the other horn served as a control. Biopsy specimens were obtained from both horns and examined histochemically. The copper concentration was determined by atomic absorption spectroscopy. The fibrinolytic activity of the control horn was found to be localized to small vessels in the outer layer of the uterine wall, while that of the endometrium was low. Plastic as well as copper IUDs increased the fibrinolytic activity which, in contrast with what was seen in the controls, was localized to the endometrium. Compared with the effect of the plastic device, the increase in the fibrinolytic activity induced by the copper device was more widespread in the endometrial area and was accompanied by an increase in the concentration of copper. These findings might help to explain why the contraceptive effect of IUDs is more reliable when they are partly coated with copper.", "contents": "Effect of copper and plastic intra-uterine devices on the fibrinolytic activity of the endometrium in the rat. The effect of copper and plastic intrauterine devices (IUD) on the fibrinolytic activity of the endometrium was studied in the rat. A copper or a plastic device was placed in one of the uterine horns, while the other horn served as a control. Biopsy specimens were obtained from both horns and examined histochemically. The copper concentration was determined by atomic absorption spectroscopy. The fibrinolytic activity of the control horn was found to be localized to small vessels in the outer layer of the uterine wall, while that of the endometrium was low. Plastic as well as copper IUDs increased the fibrinolytic activity which, in contrast with what was seen in the controls, was localized to the endometrium. Compared with the effect of the plastic device, the increase in the fibrinolytic activity induced by the copper device was more widespread in the endometrial area and was accompanied by an increase in the concentration of copper. These findings might help to explain why the contraceptive effect of IUDs is more reliable when they are partly coated with copper."}
{"id": "PMID:4395", "title": "Participation of vitamin A in the maturation of rabbit spermatozoa.", "content": "Vitamin A concentration was fluorometrically measured in epididymal and ejaculated rabbit spermatozoa and in some of the sperm cells subcellular components. The concentration of vitamin A in the epididymal cells was about one-half that observed in the ejaculated spermatozoa (2.68 as against 1.05 mug/10(8) cells) and seemed to be the same in the sperms obtained from both the head and the tail of the epididymus. The concentration of vitamin A was also found to be significantly higher in the seminal plasma than in the epididymal secretion (0.06 as against 0.039 mug/mg protein respectively). Practically all the vitamin A was found in the fractions obtained by treatment with hypotonic MgCl2 (acrosomal region) and/or with hyamine and dithiothreitol (plasma membrane). It was concluded that the sudden increase in the sperm concentration of vitamin A that occurs upon ejaculation may be required for the stabilization of the acrosomal and plasma membranes.", "contents": "Participation of vitamin A in the maturation of rabbit spermatozoa. Vitamin A concentration was fluorometrically measured in epididymal and ejaculated rabbit spermatozoa and in some of the sperm cells subcellular components. The concentration of vitamin A in the epididymal cells was about one-half that observed in the ejaculated spermatozoa (2.68 as against 1.05 mug/10(8) cells) and seemed to be the same in the sperms obtained from both the head and the tail of the epididymus. The concentration of vitamin A was also found to be significantly higher in the seminal plasma than in the epididymal secretion (0.06 as against 0.039 mug/mg protein respectively). Practically all the vitamin A was found in the fractions obtained by treatment with hypotonic MgCl2 (acrosomal region) and/or with hyamine and dithiothreitol (plasma membrane). It was concluded that the sudden increase in the sperm concentration of vitamin A that occurs upon ejaculation may be required for the stabilization of the acrosomal and plasma membranes."}
{"id": "PMID:4396", "title": "Evaluation of d-norgestrel 1.0 mg as a post-coital contraceptive.", "content": "Two hundred and ninety-eight women were followed for 2578 months (2739 'bleeding intervals') of treatment with d-Norgestrel 1.0 mg given as a post-coital oral contraceptive. Fourteen pregnancies were recorded (general failure rate, 6.5 per 100 woman/years); at least 6 of these patients did not miss any tablet (corrected failure rate, 2.8). The acceptability rates (life table method) were 0.58 and 0.40 after 6 and 12 months of follow-up. The most important medical reason for drop-out was cycle irregularities. The cycle pattern is deeply disturbed by this method of oral contraception.", "contents": "Evaluation of d-norgestrel 1.0 mg as a post-coital contraceptive. Two hundred and ninety-eight women were followed for 2578 months (2739 'bleeding intervals') of treatment with d-Norgestrel 1.0 mg given as a post-coital oral contraceptive. Fourteen pregnancies were recorded (general failure rate, 6.5 per 100 woman/years); at least 6 of these patients did not miss any tablet (corrected failure rate, 2.8). The acceptability rates (life table method) were 0.58 and 0.40 after 6 and 12 months of follow-up. The most important medical reason for drop-out was cycle irregularities. The cycle pattern is deeply disturbed by this method of oral contraception."}
{"id": "PMID:4397", "title": "\"Genital dyscrinism\" as a cause of subfertility in mice of the CBA strain.", "content": "Following four generations of inbred mating (brother-sister) in three direct lineages of CBA strain mice, sterility appeared which from that generation forward became more frequent. The genital organs in animals of both sexes were altered. There was a noticeable occurrence of cysts in the ovaries of female animals already following the third month; in mice approximately one year of age this condition was followed by cystic glandular hyperplasia of the endometrium, sometimes complicated by disturbances in blood circulation, inflammation or even malignancy. In some female animals, manifesting, due to cysts, completely degenerated ovaries, the rest of the genital system was severely atrophic. Male animals frequently showed severe atrophy of the seminiferous epithelium along with preserved interstitial cells and hypertrophic seminal vesicles. These pathological changes represent an independent nosologic unit, for which the label \"genital dyscrinism\" has been proposed. The authors have considered an endocrine mechanism as the possible cause of these pathological changes which are presumed to be genetically conditioned.", "contents": "\"Genital dyscrinism\" as a cause of subfertility in mice of the CBA strain. Following four generations of inbred mating (brother-sister) in three direct lineages of CBA strain mice, sterility appeared which from that generation forward became more frequent. The genital organs in animals of both sexes were altered. There was a noticeable occurrence of cysts in the ovaries of female animals already following the third month; in mice approximately one year of age this condition was followed by cystic glandular hyperplasia of the endometrium, sometimes complicated by disturbances in blood circulation, inflammation or even malignancy. In some female animals, manifesting, due to cysts, completely degenerated ovaries, the rest of the genital system was severely atrophic. Male animals frequently showed severe atrophy of the seminiferous epithelium along with preserved interstitial cells and hypertrophic seminal vesicles. These pathological changes represent an independent nosologic unit, for which the label \"genital dyscrinism\" has been proposed. The authors have considered an endocrine mechanism as the possible cause of these pathological changes which are presumed to be genetically conditioned."}
{"id": "PMID:4398", "title": "Motility of the rat oviductal tract isolated in different stages of the sex cycle. Effects of catecholamines.", "content": "Physiological and pharmacological characteristics of the spontaneous motility of rat oviductal tracts (the coiled oviduct plus its mesosalpinx), isolated in proestrus, estrus or metestrus, are described. The initial contractile tension (recorded following isolation) was comparable in the three stages of the cycle, but its decrement with time was greater in metestrus than in proestrus; the opposite being observed regarding the rate of contractions. Norepinephrine and phenylephrine depress motility in proestrus and metestrus, but not in estrus. The inhibition of motility during proestrus, produced by added norepinephrine, phenylephrine or isoproterenol was not modified by phenotolamine but was abolished by propranolol. During estrus, norepinephrine and phenylephrine inhibited tubal contractions of preparations incubated with phentolamine, whereas it produced a distinct stimulation in the presence of propranolol. It is concluded that: (a) the rat mesosalpinx might play some role in the motility of the whole isolated oviductal tract; (b) there are variations in the decrement with time of contractile tension and frequency of contractions in different stages of the sex cycle; (c) the effects of catecholamines upon the rat oviductal tract also varies within the cycle, probably due to influences imposed by sex hormones.", "contents": "Motility of the rat oviductal tract isolated in different stages of the sex cycle. Effects of catecholamines. Physiological and pharmacological characteristics of the spontaneous motility of rat oviductal tracts (the coiled oviduct plus its mesosalpinx), isolated in proestrus, estrus or metestrus, are described. The initial contractile tension (recorded following isolation) was comparable in the three stages of the cycle, but its decrement with time was greater in metestrus than in proestrus; the opposite being observed regarding the rate of contractions. Norepinephrine and phenylephrine depress motility in proestrus and metestrus, but not in estrus. The inhibition of motility during proestrus, produced by added norepinephrine, phenylephrine or isoproterenol was not modified by phenotolamine but was abolished by propranolol. During estrus, norepinephrine and phenylephrine inhibited tubal contractions of preparations incubated with phentolamine, whereas it produced a distinct stimulation in the presence of propranolol. It is concluded that: (a) the rat mesosalpinx might play some role in the motility of the whole isolated oviductal tract; (b) there are variations in the decrement with time of contractile tension and frequency of contractions in different stages of the sex cycle; (c) the effects of catecholamines upon the rat oviductal tract also varies within the cycle, probably due to influences imposed by sex hormones."}
{"id": "PMID:4399", "title": "The effect of prostaglandins and prostaglandin inhibitors on spermatogenesis.", "content": "The effect of the prostaglandin inhibitors, aspirin and indomethacin and of prostaglandins PGE1 and PGE2 on spermatogenesis in the mature male mouse has been studied. Aspirin at 100 mg/kg and at 200 mg/kg, and indomethacin at 1.0 mg/kg given orally twice a day for fifteen days produced a marked increase in spermatogenesis. The number of step 7 spermatids increased significantly over controls at about the same rate in all three groups. No significant changes in seminal vesicle weight or testicular weight was noted, although testicular weight did show an increase. Administration of prostaglandins E1 and E2 subcutaneously in doses of either 2 mg/kg or 3 mg/kg once a day for fifteen days produced a marked decrease in spermatogenesis. Step 7 spermatids decreased significantly at both dosage levels of PGE2 and at the higher dosage level of PGE1. Spermatocyte showed a significant decrease at the higher dose of PGE2. Testicular weight showed a significant decrease at the higher dose of PGE2. Seminal vesicle weight showed a significant decrease at the lower dose of PGE1 and at the higher dose of PGE2. Epididymal weight decreased at the higher dose of PGE2. Increased numbers of exfoliated immature germ cells and mature spermatozoa were observed in the epididymus of both the PGE1 and PGE2 treated animals.", "contents": "The effect of prostaglandins and prostaglandin inhibitors on spermatogenesis. The effect of the prostaglandin inhibitors, aspirin and indomethacin and of prostaglandins PGE1 and PGE2 on spermatogenesis in the mature male mouse has been studied. Aspirin at 100 mg/kg and at 200 mg/kg, and indomethacin at 1.0 mg/kg given orally twice a day for fifteen days produced a marked increase in spermatogenesis. The number of step 7 spermatids increased significantly over controls at about the same rate in all three groups. No significant changes in seminal vesicle weight or testicular weight was noted, although testicular weight did show an increase. Administration of prostaglandins E1 and E2 subcutaneously in doses of either 2 mg/kg or 3 mg/kg once a day for fifteen days produced a marked decrease in spermatogenesis. Step 7 spermatids decreased significantly at both dosage levels of PGE2 and at the higher dosage level of PGE1. Spermatocyte showed a significant decrease at the higher dose of PGE2. Testicular weight showed a significant decrease at the higher dose of PGE2. Seminal vesicle weight showed a significant decrease at the lower dose of PGE1 and at the higher dose of PGE2. Epididymal weight decreased at the higher dose of PGE2. Increased numbers of exfoliated immature germ cells and mature spermatozoa were observed in the epididymus of both the PGE1 and PGE2 treated animals."}
{"id": "PMID:4400", "title": "Low fertility rate in vasovasostomized males and its possible immunologic mechanism.", "content": "Contradictory views have been expressed about the role of the various antisperm antibodies which develop after vasoligation. The present study was conducted in 50 normal fertile males, 50 vasectomized subjects and 25 subjects after recanalization of their vas deferens in order to investigate the development of various anti-sperm antibodies after vasectomy, along with their incidence, their persistence after successful relief of vaso-obstruction by vasovasostomy and their role in the causation of infertility in vasoanatomized normospermia males. Sperm agglutinating, immobilizing and haemagglutinating antibodies showed rises in titres with increase during the post-vasectomy period, indicating continuous antigenic stimulus. Age, post-operative complications and blood group did not seem to alter the results. 86% of subjects developed antisperm agglutinins, mostly tail-to-tail type (54.5%), 1-12 years after vasoligation, while only 2% of fertile men had circulating spermagglutinins. A lower incidence of positive sperm in the immobilization test than in the agglutination test suggests either that different antibodies are detected by these two tests or these tests have differing sensitivities. Of the 25 vasovasostomized subject, 13 (52%) cases became normospermic and 4 (16%) oligospermic while 8 (32%) remained azoospermics. Except for 3 oligospermic subjects, all had circulating spermagglutinins. Among the 13 normospermic vasovasostomized persons, a significant correlation was found between the titres of circulating antisperm agglutinins and autoagglutination of spermatozoa in their ejaculates; and also between the sperm immobilization values of their sera and the degree of their sperm motility. Three normospermic recanalized men, having low levels of sperm agglutinins and haemagglutinins with normal seminogram and no sperm immobilizing antibody, successfully impregnated their wives. Another 10 vasovasotomized infertile subjects had sperm agglutinins in significant titre; 5 showed positive sperm immobilization values, a similar number showed autoagglutination of sperm, while a decreased degree of motility of sperms was noted in 6 cases. Thus there was a significant correlation between the titres of anti-sperm antibodies and autoagglutination of spermatozoa, which might be an important cause of male infertility after successful anatomic relief of vasoobstruction. Histological studies of testicular biopsy showed normal spermatogenesis in azoospermic recanalized subjects, although they had high levels of antisperm antibodies. This suggests that these antibodies do not affect normal spermatogenesis, and sperm counts.", "contents": "Low fertility rate in vasovasostomized males and its possible immunologic mechanism. Contradictory views have been expressed about the role of the various antisperm antibodies which develop after vasoligation. The present study was conducted in 50 normal fertile males, 50 vasectomized subjects and 25 subjects after recanalization of their vas deferens in order to investigate the development of various anti-sperm antibodies after vasectomy, along with their incidence, their persistence after successful relief of vaso-obstruction by vasovasostomy and their role in the causation of infertility in vasoanatomized normospermia males. Sperm agglutinating, immobilizing and haemagglutinating antibodies showed rises in titres with increase during the post-vasectomy period, indicating continuous antigenic stimulus. Age, post-operative complications and blood group did not seem to alter the results. 86% of subjects developed antisperm agglutinins, mostly tail-to-tail type (54.5%), 1-12 years after vasoligation, while only 2% of fertile men had circulating spermagglutinins. A lower incidence of positive sperm in the immobilization test than in the agglutination test suggests either that different antibodies are detected by these two tests or these tests have differing sensitivities. Of the 25 vasovasostomized subject, 13 (52%) cases became normospermic and 4 (16%) oligospermic while 8 (32%) remained azoospermics. Except for 3 oligospermic subjects, all had circulating spermagglutinins. Among the 13 normospermic vasovasostomized persons, a significant correlation was found between the titres of circulating antisperm agglutinins and autoagglutination of spermatozoa in their ejaculates; and also between the sperm immobilization values of their sera and the degree of their sperm motility. Three normospermic recanalized men, having low levels of sperm agglutinins and haemagglutinins with normal seminogram and no sperm immobilizing antibody, successfully impregnated their wives. Another 10 vasovasotomized infertile subjects had sperm agglutinins in significant titre; 5 showed positive sperm immobilization values, a similar number showed autoagglutination of sperm, while a decreased degree of motility of sperms was noted in 6 cases. Thus there was a significant correlation between the titres of anti-sperm antibodies and autoagglutination of spermatozoa, which might be an important cause of male infertility after successful anatomic relief of vasoobstruction. Histological studies of testicular biopsy showed normal spermatogenesis in azoospermic recanalized subjects, although they had high levels of antisperm antibodies. This suggests that these antibodies do not affect normal spermatogenesis, and sperm counts."}
{"id": "PMID:4403", "title": "Studies on urinary arylsulphatase activity in vitamin A deficient rats.", "content": "Urinary arylsulphatases (E.C.3.1.6.1) A and B were increased in male rats fasted for 24 hours. Excretion of non dialysable protein nitrogen decreased whereas creatinine excretion increased. On refeeding diet arylsulphatase A activity was restored to normal whereas arylsulphatase B was not normalised. A single oral supplementation of vitamin A acetate (20 000 IU) to rats fasted for 24 hours resulted in a significant reduction of both arylsulphatase A and B eventhough no further reduction of protein nitrogen excretion was evident. In vitamin A deficient male rats significant reduction in urinary excretion of both arylsulphatases A and B occured. In a smaller number of female rats depression of only arylsulphatase A was observed. This effect of vitamin A deficiency leading to reduced urinary arylsulphatase activity was evident even at the \"weight plateau\" stage when no reduction in food intake or growth had  occurred. These results suggest a possible direct or indirect role for vitamin A on urinary excretion pattern of arylsulphatases presumably released from lysosomes of tissues.", "contents": "Studies on urinary arylsulphatase activity in vitamin A deficient rats. Urinary arylsulphatases (E.C.3.1.6.1) A and B were increased in male rats fasted for 24 hours. Excretion of non dialysable protein nitrogen decreased whereas creatinine excretion increased. On refeeding diet arylsulphatase A activity was restored to normal whereas arylsulphatase B was not normalised. A single oral supplementation of vitamin A acetate (20 000 IU) to rats fasted for 24 hours resulted in a significant reduction of both arylsulphatase A and B eventhough no further reduction of protein nitrogen excretion was evident. In vitamin A deficient male rats significant reduction in urinary excretion of both arylsulphatases A and B occured. In a smaller number of female rats depression of only arylsulphatase A was observed. This effect of vitamin A deficiency leading to reduced urinary arylsulphatase activity was evident even at the \"weight plateau\" stage when no reduction in food intake or growth had  occurred. These results suggest a possible direct or indirect role for vitamin A on urinary excretion pattern of arylsulphatases presumably released from lysosomes of tissues."}
{"id": "PMID:4404", "title": "Effect of long-term starvation on the rat liver lysosomes.", "content": "The effect of 120- and 240-h starvation on rats hepatocytes ultrastructure and particularly the changes of the lysosomes were studied. Eelectronmicroscopically and cytochemically there have been observed diminution of the number of mitochondria and degranulation and vacuolzation of the ER. At the same time Golgi complex was hypertrophied and the number of lysosomes was much increased, mainly those of the autophagic type. Biochemically was shown, that the activity of some acid hydrolases (beta-glucosidase, alpha- and beta-galactosidases, beta-N-acetylglucosaminidase, beta-glucuronidase and arylsulphatases A and B) in the liver of starved rats was markedly expressed. The sedimentation properties of the lysosomes and the lysosomal membrane stability was damaged as well. The data received have been discussed in the light of the reconstructive role of lysosomes.", "contents": "Effect of long-term starvation on the rat liver lysosomes. The effect of 120- and 240-h starvation on rats hepatocytes ultrastructure and particularly the changes of the lysosomes were studied. Eelectronmicroscopically and cytochemically there have been observed diminution of the number of mitochondria and degranulation and vacuolzation of the ER. At the same time Golgi complex was hypertrophied and the number of lysosomes was much increased, mainly those of the autophagic type. Biochemically was shown, that the activity of some acid hydrolases (beta-glucosidase, alpha- and beta-galactosidases, beta-N-acetylglucosaminidase, beta-glucuronidase and arylsulphatases A and B) in the liver of starved rats was markedly expressed. The sedimentation properties of the lysosomes and the lysosomal membrane stability was damaged as well. The data received have been discussed in the light of the reconstructive role of lysosomes."}
{"id": "PMID:4405", "title": "Hypogastric carotid bypass for Takayasu's disease.", "content": "Two cases of Takayasu's disease are presented which were successfully resolved by a Dacron graft from the right hypogastric artery to the right internal carotid artery. We recommend this bypass procedure of connecting the hypogastric artery to one of the aortic branches. Medical treatment with antibiotics, steroids and anti-coagulants has not been satisfactory.", "contents": "Hypogastric carotid bypass for Takayasu's disease. Two cases of Takayasu's disease are presented which were successfully resolved by a Dacron graft from the right hypogastric artery to the right internal carotid artery. We recommend this bypass procedure of connecting the hypogastric artery to one of the aortic branches. Medical treatment with antibiotics, steroids and anti-coagulants has not been satisfactory."}
{"id": "PMID:4406", "title": "Psychopharmacology research ward. Ten years' experience.", "content": "The differences between the results of controlled clinical research and the experiences of the practitioners can be attributed to a certain extent to the artificiality of the setting in which controlled studies are performed. The system developed in the wards of the Department of Psychopharmacology of the Institute of Psychiatry in Prague is an attempt to overcome some of these difficulties. Certain similarities exist between this system called continuous controlled trial and 'silent' trial proposed by Ross et al. The main characteristics of the system are: (1) all patients admitted to the ward are assigned to the trial without exception; (2) the trial goes on continuously without interruption for more than 10 years; (3) except that the patients do not know the quality of drugs administered they do not realize any difference between this research setting and the usual routine treatment. The advantages of this system are: reduction of artificiality; the possibility to perform early clinical trials in controlled conditions and to shorten the usual three-phase testing of a new drug; the possibility to perform long-term, longitudinal studies with individual patients admitted several times in double-blind conditions.", "contents": "Psychopharmacology research ward. Ten years' experience. The differences between the results of controlled clinical research and the experiences of the practitioners can be attributed to a certain extent to the artificiality of the setting in which controlled studies are performed. The system developed in the wards of the Department of Psychopharmacology of the Institute of Psychiatry in Prague is an attempt to overcome some of these difficulties. Certain similarities exist between this system called continuous controlled trial and 'silent' trial proposed by Ross et al. The main characteristics of the system are: (1) all patients admitted to the ward are assigned to the trial without exception; (2) the trial goes on continuously without interruption for more than 10 years; (3) except that the patients do not know the quality of drugs administered they do not realize any difference between this research setting and the usual routine treatment. The advantages of this system are: reduction of artificiality; the possibility to perform early clinical trials in controlled conditions and to shorten the usual three-phase testing of a new drug; the possibility to perform long-term, longitudinal studies with individual patients admitted several times in double-blind conditions."}
{"id": "PMID:4407", "title": "[Comparative study of three psychotropics for treatment of depressions].", "content": "The effect of three anti-depressive psychotropes (Clorimipramine, Doxepine and Dibenzepine) was studied in 107 depressed patients. In each patient the mean value of twelve symptoms was evaluated and compared weekly (for 4 weeks), by statistical methods. In addition, the effect of each drug was analysed in personality stratus. A thymeretic and thymoanaleptic rapid action on 'corporality' and 'endotimic-vital' layer was found with Clorimipramine. Doxepine acts rapidly with sedative and anxiolitic actions on reactive symptoms related with personality super-structures having long term anti-depressive effects. Dibenzepine has a thymeretic rapid and intensive action and a slow thymoanaleptic effect on the same personality stratus of Clorimipramine.", "contents": "[Comparative study of three psychotropics for treatment of depressions]. The effect of three anti-depressive psychotropes (Clorimipramine, Doxepine and Dibenzepine) was studied in 107 depressed patients. In each patient the mean value of twelve symptoms was evaluated and compared weekly (for 4 weeks), by statistical methods. In addition, the effect of each drug was analysed in personality stratus. A thymeretic and thymoanaleptic rapid action on 'corporality' and 'endotimic-vital' layer was found with Clorimipramine. Doxepine acts rapidly with sedative and anxiolitic actions on reactive symptoms related with personality super-structures having long term anti-depressive effects. Dibenzepine has a thymeretic rapid and intensive action and a slow thymoanaleptic effect on the same personality stratus of Clorimipramine."}
{"id": "PMID:4411", "title": "Properties of rat lens phosphofructokinase.", "content": "Two interconvertible forms of phosphofructokinase (PFK) have been eluted from a DEAE-cellulose column from the supernatant fraction of rat lens homogenates centrifuged at 96,000 x g for 1 hour at 0 to 4 degrees C. The interconversion can be manipulated by a change in the pH of the extracting and eluting buffers. PFK-I is the dominant form at pH between 7.4 to 7.05, while PFK-II dominates at pH 7.4 to 8.2. PFK-II is believed to be the functional form; it is inhibited by high concentrations of ATP and the inhibitory effect is enhanced by more acidic pH. Fructose-6-phosphate counteracts ATP inhibition, but the most potent de-inhibitors are ADP and AMP. Among the inorganic ions tested, sulfate, phosphate, ammonium, and potassium also de-inhibit, whereas calcium further inhibits the enzyme. The behavior of PFK under physiologic conditions and the significance of the presence of two forms of PFK in the lens are discussed.", "contents": "Properties of rat lens phosphofructokinase. Two interconvertible forms of phosphofructokinase (PFK) have been eluted from a DEAE-cellulose column from the supernatant fraction of rat lens homogenates centrifuged at 96,000 x g for 1 hour at 0 to 4 degrees C. The interconversion can be manipulated by a change in the pH of the extracting and eluting buffers. PFK-I is the dominant form at pH between 7.4 to 7.05, while PFK-II dominates at pH 7.4 to 8.2. PFK-II is believed to be the functional form; it is inhibited by high concentrations of ATP and the inhibitory effect is enhanced by more acidic pH. Fructose-6-phosphate counteracts ATP inhibition, but the most potent de-inhibitors are ADP and AMP. Among the inorganic ions tested, sulfate, phosphate, ammonium, and potassium also de-inhibit, whereas calcium further inhibits the enzyme. The behavior of PFK under physiologic conditions and the significance of the presence of two forms of PFK in the lens are discussed."}
{"id": "PMID:4412", "title": "Effects of pregnancy on the development of acute uremic syndrome in the rat.", "content": "We evaluated the contributory role which gestational metabolic adaptions may play in the development of acute uremic syndrome in rats by studying the effects of nephrectomy in pregnant and nonpregnant animals. Whereas no significant differences in creatinine and uric acid concentrations were found between control and pregnant rats, urea concentrations were significantly lower in the pregnant animals before, as well as well as 6, 12 and 24 h after, bilateral nephrectomy. It is suggested that creatinine production, which is related to muscle mass, is not altered during late gestation, whereas urea synthesis, which is affected by catabolic and anabolic factors, is significantly reduced.", "contents": "Effects of pregnancy on the development of acute uremic syndrome in the rat. We evaluated the contributory role which gestational metabolic adaptions may play in the development of acute uremic syndrome in rats by studying the effects of nephrectomy in pregnant and nonpregnant animals. Whereas no significant differences in creatinine and uric acid concentrations were found between control and pregnant rats, urea concentrations were significantly lower in the pregnant animals before, as well as well as 6, 12 and 24 h after, bilateral nephrectomy. It is suggested that creatinine production, which is related to muscle mass, is not altered during late gestation, whereas urea synthesis, which is affected by catabolic and anabolic factors, is significantly reduced."}
{"id": "PMID:4414", "title": "Blood-gas analysis and the assessment of acid-base status.", "content": "In this article the more common kinds of acid-base disorders have been discussed. To accurately assess the kind of acid-base disturbance found in a patient, the clinician must know the arterial pH, PaCO2, and the [HCO-3] in arterial blood. Acid-base disturbances are associated with fluid and electrolyte disturbances. Potassium balance is often upset in acid-base disturbances. Accurate determination of K+ balance requires serial or repeated determinations of plasma K+ concentration as well as careful clinical monitoring.", "contents": "Blood-gas analysis and the assessment of acid-base status. In this article the more common kinds of acid-base disorders have been discussed. To accurately assess the kind of acid-base disturbance found in a patient, the clinician must know the arterial pH, PaCO2, and the [HCO-3] in arterial blood. Acid-base disturbances are associated with fluid and electrolyte disturbances. Potassium balance is often upset in acid-base disturbances. Accurate determination of K+ balance requires serial or repeated determinations of plasma K+ concentration as well as careful clinical monitoring."}
{"id": "PMID:4418", "title": "Intracellular distinction between peroxidase and catalase in exocrine cells of rat lacrimal gland: a biochemical and cytochemical study.", "content": "The lacrimal gland (Glandula orbitalis externa) of rat contains both peroxidase and catalase and was used as a model for biochemical and cytochemical distinction between peroxidase and catalase. Both enzymes were isolated by ammonium sulfate precipitation from tissue homogenates, and the effects of fixation with glutaraldehyde and various conditions of incubation were investigated colorimetrically using DAB as hydrogen donor. The lacrimal gland peroxidase is strongly inhibited by glutaraldehyde treatment. In contrast, for catalase the fixation with glutaraldehyde is the prerequistie for demonstration of its peroxidatic activity. The maximal peroxidatic activity was obtained after treatment of catalase with 3% glutaraldehyde, higher concentrations being inhibitory. For lacrimal gland peroxidase, the maximal rate of oxidation of DAB is at pH 6.5, whereas for catalase it is at pH 10.5. The optimal concentration of H2O2 for lacrimal gland peroxidase is at 10(-3)M and for peroxidatic activity of catalase at 10(-1)M. These optimal conditions obtained biochemically were applied to tissue sections of rat lacrimal gland. After the fixation of tissue with a low concentration of glutaraldehyde and incubation in the DAB medium at neutral pH containing 10(-3)M H2O2 (Peroxidase medium), the reaction product was localized in the cisternae of the rough endoplasmic reticulum, in elements of the Golgi apparatus, and in secretory granules. After the fixation of tissue with 3% glutaraldehyde and incubation in the DAB-medium containing 10(-1)M H2O2 and at pH 10.5 (catalase medium), the staining in the endoplasmic reticulum, the Golgi-apparatus and in secretory granules was completely inhibited and reaction product was localized exclusively in small (0.2-0.5 mu) particles similar to small peroxisomes described in various other cell-types.", "contents": "Intracellular distinction between peroxidase and catalase in exocrine cells of rat lacrimal gland: a biochemical and cytochemical study. The lacrimal gland (Glandula orbitalis externa) of rat contains both peroxidase and catalase and was used as a model for biochemical and cytochemical distinction between peroxidase and catalase. Both enzymes were isolated by ammonium sulfate precipitation from tissue homogenates, and the effects of fixation with glutaraldehyde and various conditions of incubation were investigated colorimetrically using DAB as hydrogen donor. The lacrimal gland peroxidase is strongly inhibited by glutaraldehyde treatment. In contrast, for catalase the fixation with glutaraldehyde is the prerequistie for demonstration of its peroxidatic activity. The maximal peroxidatic activity was obtained after treatment of catalase with 3% glutaraldehyde, higher concentrations being inhibitory. For lacrimal gland peroxidase, the maximal rate of oxidation of DAB is at pH 6.5, whereas for catalase it is at pH 10.5. The optimal concentration of H2O2 for lacrimal gland peroxidase is at 10(-3)M and for peroxidatic activity of catalase at 10(-1)M. These optimal conditions obtained biochemically were applied to tissue sections of rat lacrimal gland. After the fixation of tissue with a low concentration of glutaraldehyde and incubation in the DAB medium at neutral pH containing 10(-3)M H2O2 (Peroxidase medium), the reaction product was localized in the cisternae of the rough endoplasmic reticulum, in elements of the Golgi apparatus, and in secretory granules. After the fixation of tissue with 3% glutaraldehyde and incubation in the DAB-medium containing 10(-1)M H2O2 and at pH 10.5 (catalase medium), the staining in the endoplasmic reticulum, the Golgi-apparatus and in secretory granules was completely inhibited and reaction product was localized exclusively in small (0.2-0.5 mu) particles similar to small peroxisomes described in various other cell-types."}
{"id": "PMID:4415", "title": "Arterial blood-gas interpretations in the respiratory intensive-care unit.", "content": "The role of the nurse in the respiratory intensive-care unit requires increased sophistication as our knowledge of the patient becomes more complex. This expanded role should include a thorough understanding of disturbances in acid-base balance, the relationship of PaCO2 to ventilation, the difference in acute and chronic respiratory problems, and the causes and treatment of hypoxemia. The ability to analyze and evaluate blood-gas determinations is simply one more important tool the nurse may utilize in the care and treatment of the critically ill patient.", "contents": "Arterial blood-gas interpretations in the respiratory intensive-care unit. The role of the nurse in the respiratory intensive-care unit requires increased sophistication as our knowledge of the patient becomes more complex. This expanded role should include a thorough understanding of disturbances in acid-base balance, the relationship of PaCO2 to ventilation, the difference in acute and chronic respiratory problems, and the causes and treatment of hypoxemia. The ability to analyze and evaluate blood-gas determinations is simply one more important tool the nurse may utilize in the care and treatment of the critically ill patient."}
{"id": "PMID:4419", "title": "Antimycin A fermentation. II. Fermentation in aerated-agitated fermenters.", "content": "Fermentation characteristics, previously studied in shake flasks, were reproduced in aerated-agitated fermenters, using three strains of Streptomyces sp. which had been selected for their high antimycin A productivity in shake flasks. Fermentation in fermenters was run in three stages. The medium consisted of soy flour, glucose, ammonium sulfate and calcium carbonate; initial pH was 7.2 approximately 7.5, and temperature 25 degrees C. The course of fermentation was then modified to encourage maximal growth and eliminate the intermediate lag period observed in shake flasks. Useful corrections included continuous addition of soybean oil at 1.25 %/day and maintenance of pH at 6 by addition of ammonium hydroxide on demand. The ammonium hydroxide added also served as a rapidly utilized nitrogen source and could not be replace by NaOH or KOH. Under optimal conditions antimycin A was produced at constant rate from the second to the sixth day, when maximum yields of more than 9 g/liter were attained. A procedure for antimycin A extraction is described.", "contents": "Antimycin A fermentation. II. Fermentation in aerated-agitated fermenters. Fermentation characteristics, previously studied in shake flasks, were reproduced in aerated-agitated fermenters, using three strains of Streptomyces sp. which had been selected for their high antimycin A productivity in shake flasks. Fermentation in fermenters was run in three stages. The medium consisted of soy flour, glucose, ammonium sulfate and calcium carbonate; initial pH was 7.2 approximately 7.5, and temperature 25 degrees C. The course of fermentation was then modified to encourage maximal growth and eliminate the intermediate lag period observed in shake flasks. Useful corrections included continuous addition of soybean oil at 1.25 %/day and maintenance of pH at 6 by addition of ammonium hydroxide on demand. The ammonium hydroxide added also served as a rapidly utilized nitrogen source and could not be replace by NaOH or KOH. Under optimal conditions antimycin A was produced at constant rate from the second to the sixth day, when maximum yields of more than 9 g/liter were attained. A procedure for antimycin A extraction is described."}
{"id": "PMID:4421", "title": "Nutritionally defined conditions for germination of Streptomyces viridochromogenes spores.", "content": "Spores of Streptomyces viridochromogenes were removed from the surface of solid media with glass beads and suspended in a buffer-detergent solution. Addition of yeast extract and glucose resulted in rapid loss of refractility of the spores. Appearance of germ tubes followed. Germination was accompanied by a decrease in the optical density (OD) of the suspension. The OD decrease was used as an assay for germination. A defined germination medium (DGM) comprised of L-alanine, L-glutamic acid, adenosine, para-aminobenzoic acid, and calcium and magnesium ions provided a germination rate nearly equal to that of complex media. The germination rate was essentially the same if D-alanine and D-glutamate replaced the L-isomers. The optimum pH and temperature for germination were 7.0 and 35 C. Germination was absolutely dependent on the presence of CO2. Spores harvested after growth for longer periods than the usual time (10 days) became less germinable in DGM. The same was observed for spores grown at 37 C as compared with 30 C. Spores incubated in DGM for various time periods before being transferred to a buffer solution did not continue to germinate. Spores harvested after growth of eight species of Streptomyces did not show a decrease in OD when incubated in yeast extract medium. Another strain of S. viridochromogenes did exhibit an OD decrease in the medium. Comparative properties of spores of streptomycetes, fungi, and bacilli are discussed.", "contents": "Nutritionally defined conditions for germination of Streptomyces viridochromogenes spores. Spores of Streptomyces viridochromogenes were removed from the surface of solid media with glass beads and suspended in a buffer-detergent solution. Addition of yeast extract and glucose resulted in rapid loss of refractility of the spores. Appearance of germ tubes followed. Germination was accompanied by a decrease in the optical density (OD) of the suspension. The OD decrease was used as an assay for germination. A defined germination medium (DGM) comprised of L-alanine, L-glutamic acid, adenosine, para-aminobenzoic acid, and calcium and magnesium ions provided a germination rate nearly equal to that of complex media. The germination rate was essentially the same if D-alanine and D-glutamate replaced the L-isomers. The optimum pH and temperature for germination were 7.0 and 35 C. Germination was absolutely dependent on the presence of CO2. Spores harvested after growth for longer periods than the usual time (10 days) became less germinable in DGM. The same was observed for spores grown at 37 C as compared with 30 C. Spores incubated in DGM for various time periods before being transferred to a buffer solution did not continue to germinate. Spores harvested after growth of eight species of Streptomyces did not show a decrease in OD when incubated in yeast extract medium. Another strain of S. viridochromogenes did exhibit an OD decrease in the medium. Comparative properties of spores of streptomycetes, fungi, and bacilli are discussed."}
{"id": "PMID:4422", "title": "Effect of pH on competence development and deoxyribonucleic acid uptake in Streptococcus sanguis (Wicky).", "content": "Streptococcus sanguis (Wicky) cells, strain WE4, developed little or no competence and failed to autolyze in permissive conditions when treated with competence factor (CF) below PH 7.0. This lack of activity was directly correlated with the inability of the cells to bind or take up CF at pH values of 5.5, 6.0, and 6.5. On the other hand, competent cells bound deoxyribonucleic acid molecules maximally below pH 7.0 and transformed maximally at pH 6.5. Deoxyribonucleic acid was optimally bound to cells in a deoxyribonuclease-resistant form at pH values between 7.0 and 8.5. Concomitant with this binding, undefined acid-soluble DNA fragments appeared in the culture menstrua. CF binding and uptake by cells was not only influenced by low pH but also by low temperature. At 0 C, WE4 cells bound only 4% of the input CF and took up less than 1% into a trypsin-insensitive state compared to cells treated at 37 C. Cells treated with CF at 0 C did not autolyze when transferred to permissive conditions. The results presented in this report extend earlier findings that showed that competence development and autolysis are related to the uptake of CF.", "contents": "Effect of pH on competence development and deoxyribonucleic acid uptake in Streptococcus sanguis (Wicky). Streptococcus sanguis (Wicky) cells, strain WE4, developed little or no competence and failed to autolyze in permissive conditions when treated with competence factor (CF) below PH 7.0. This lack of activity was directly correlated with the inability of the cells to bind or take up CF at pH values of 5.5, 6.0, and 6.5. On the other hand, competent cells bound deoxyribonucleic acid molecules maximally below pH 7.0 and transformed maximally at pH 6.5. Deoxyribonucleic acid was optimally bound to cells in a deoxyribonuclease-resistant form at pH values between 7.0 and 8.5. Concomitant with this binding, undefined acid-soluble DNA fragments appeared in the culture menstrua. CF binding and uptake by cells was not only influenced by low pH but also by low temperature. At 0 C, WE4 cells bound only 4% of the input CF and took up less than 1% into a trypsin-insensitive state compared to cells treated at 37 C. Cells treated with CF at 0 C did not autolyze when transferred to permissive conditions. The results presented in this report extend earlier findings that showed that competence development and autolysis are related to the uptake of CF."}
{"id": "PMID:4423", "title": "Control of inositol biosynthesis in Saccharomyces cerevisiae: properties of a repressible enzyme system in extracts of wild-type (Ino+) cells.", "content": "Inositol biosynthesis was studied in soluble, cell extracts of a wild-type (Ino) strain of Saccharomyces cerevisiae.  Two reactions were detected: (i) conversion of D-glucose-6-phosphate to a phosphorylated form of inositol, presumably inositol-1-phosphate (IP synthethase, EC5.5.1.4), and (ii) conversion of phosphorylated inositol to inositol (IP phosphatase, EC3.1.3.25).  The in vitro rate of conversion of glucose-6-phosphate to inositol was proportional to incubaion time and enzyme concentration.  The pH optimum was 7.0.  The synthesis of inositol required oxidized nicotinamide adenine dinucleotide (NAD) and was stimulated byNH4C1 and MgC12.  NADP substituted poorly for NAD, and NADH inhibitedthe reaction.  Phosphorylated inositol accumulated in the absence of MgC12, suggesting that inositol-phosphate is an intermediate in the pathway and that Mg ions stimulate the dephosphorylation of inositol-phosphate.  IP synthetase was inhibited approximately 20% in the presence of inositol in the reaction mixture at concentrations exceeding 1 mM.  The enzyme was repressed approximately 50-fold when inositol was present in the growth medium at concentrations exceeding 50 muM.  IP synthetase reached the fully repressed level approximately 10 h after the addition of inositol to logarithmic cultures grown in the absence of inositol.  The specific activity of the enzyme increased with time in logarithmically growing cultures lacking inositol andapproached the fully depressed level as the cells entered stationary phase.", "contents": "Control of inositol biosynthesis in Saccharomyces cerevisiae: properties of a repressible enzyme system in extracts of wild-type (Ino+) cells. Inositol biosynthesis was studied in soluble, cell extracts of a wild-type (Ino) strain of Saccharomyces cerevisiae.  Two reactions were detected: (i) conversion of D-glucose-6-phosphate to a phosphorylated form of inositol, presumably inositol-1-phosphate (IP synthethase, EC5.5.1.4), and (ii) conversion of phosphorylated inositol to inositol (IP phosphatase, EC3.1.3.25).  The in vitro rate of conversion of glucose-6-phosphate to inositol was proportional to incubaion time and enzyme concentration.  The pH optimum was 7.0.  The synthesis of inositol required oxidized nicotinamide adenine dinucleotide (NAD) and was stimulated byNH4C1 and MgC12.  NADP substituted poorly for NAD, and NADH inhibitedthe reaction.  Phosphorylated inositol accumulated in the absence of MgC12, suggesting that inositol-phosphate is an intermediate in the pathway and that Mg ions stimulate the dephosphorylation of inositol-phosphate.  IP synthetase was inhibited approximately 20% in the presence of inositol in the reaction mixture at concentrations exceeding 1 mM.  The enzyme was repressed approximately 50-fold when inositol was present in the growth medium at concentrations exceeding 50 muM.  IP synthetase reached the fully repressed level approximately 10 h after the addition of inositol to logarithmic cultures grown in the absence of inositol.  The specific activity of the enzyme increased with time in logarithmically growing cultures lacking inositol andapproached the fully depressed level as the cells entered stationary phase."}
{"id": "PMID:4424", "title": "Heat activation of Streptomyces viridochromogenes spores.", "content": "The lag period preceding germination of Streptomyces viridochromogenes spores during incubation in a defined germination medium was completely eliminated by a gentle heat shock. The rate of germination was not affected. The optimum pH for activation extended from 6.0 to 9.6. The time of heating required for maximum activation was 1 min at 60 C, 2 to 5 min at 55 C, 20 min at 50 C, and 40 to 50 min at 45 C. Activated spores had the same temperature and pH optima and nutritional requirements for germination as unactivated spores. Activated spores deactivated during incubation for 8 h at 25 C and were activated again by a second heat shock. Spores that had been aged for 4 weeks or longer did not germinate in the defined germination medium unless they were first heat activated.", "contents": "Heat activation of Streptomyces viridochromogenes spores. The lag period preceding germination of Streptomyces viridochromogenes spores during incubation in a defined germination medium was completely eliminated by a gentle heat shock. The rate of germination was not affected. The optimum pH for activation extended from 6.0 to 9.6. The time of heating required for maximum activation was 1 min at 60 C, 2 to 5 min at 55 C, 20 min at 50 C, and 40 to 50 min at 45 C. Activated spores had the same temperature and pH optima and nutritional requirements for germination as unactivated spores. Activated spores deactivated during incubation for 8 h at 25 C and were activated again by a second heat shock. Spores that had been aged for 4 weeks or longer did not germinate in the defined germination medium unless they were first heat activated."}
{"id": "PMID:4425", "title": "Glucose transport in isolated prosthecae of Asticcacaulis biprosthecum.", "content": "Active transport of glucose in prosthecae isolated from cells of Asticcacaulis biprosthecum was stimulated by the non-physiological electron donor N, N, N', N'-tetramethyl-p-phenylenediamine dihydrochloride. Glucose uptake was mediated by two transport systems; the apparent Km of the high-affinity system was 1.8 muM and that of the low-affinity system was 34 muM. Free glucose accumulated within prosthecae at a concentration 60 to 200 times above that present externally, depending on the Km of the system being observed. The glucose transport system in prosthecae was stereospecific for D-glucose, and neither methyl alpha-D-glucopyranoside nor 2-deoxyglucose was transported. Uptake of glucose was inhibited by N-ethylmaleimide (NEM) and p-chloromercuribenzoate (PCMB), and the inhibition by PCMB but not by NEM was reversed by dithiothreitol. Glucose uptake was also inhibited by the uncoupling agents 5-chloro-3-t-butyl-2'-nitrosalicylanilide (S-13), 5-chloro-3-(p-chlorophenyl)-4'-chlorosalicylanilide (S-6), and carbonyl-cyanide m-chlorophenylhydrazone (CCCP) and by the respiratory inhibitor KCN. Efflux of glucose from preloaded prosthecae was induced by PCMB and KCN, but not by S-13 or CCCP. Glucose uptake was not affected by arsenate or an inhibitor of membrane-bound adenosine triphosphatases, N, N'-dicyclohexylcarbodiimide. The lack of inhibition by these two compounds, combined with the extremely low levels of adenosine 5'-triphosphate present in prosthecae, indicates that adenosine 5'-triphosphate is not involved in the transport of glucose by prosthecae.", "contents": "Glucose transport in isolated prosthecae of Asticcacaulis biprosthecum. Active transport of glucose in prosthecae isolated from cells of Asticcacaulis biprosthecum was stimulated by the non-physiological electron donor N, N, N', N'-tetramethyl-p-phenylenediamine dihydrochloride. Glucose uptake was mediated by two transport systems; the apparent Km of the high-affinity system was 1.8 muM and that of the low-affinity system was 34 muM. Free glucose accumulated within prosthecae at a concentration 60 to 200 times above that present externally, depending on the Km of the system being observed. The glucose transport system in prosthecae was stereospecific for D-glucose, and neither methyl alpha-D-glucopyranoside nor 2-deoxyglucose was transported. Uptake of glucose was inhibited by N-ethylmaleimide (NEM) and p-chloromercuribenzoate (PCMB), and the inhibition by PCMB but not by NEM was reversed by dithiothreitol. Glucose uptake was also inhibited by the uncoupling agents 5-chloro-3-t-butyl-2'-nitrosalicylanilide (S-13), 5-chloro-3-(p-chlorophenyl)-4'-chlorosalicylanilide (S-6), and carbonyl-cyanide m-chlorophenylhydrazone (CCCP) and by the respiratory inhibitor KCN. Efflux of glucose from preloaded prosthecae was induced by PCMB and KCN, but not by S-13 or CCCP. Glucose uptake was not affected by arsenate or an inhibitor of membrane-bound adenosine triphosphatases, N, N'-dicyclohexylcarbodiimide. The lack of inhibition by these two compounds, combined with the extremely low levels of adenosine 5'-triphosphate present in prosthecae, indicates that adenosine 5'-triphosphate is not involved in the transport of glucose by prosthecae."}
{"id": "PMID:4426", "title": "Defective synthesis of lipid intermediates for peptidoglycan formation in a stabilized L-form of Streptococcus pyogenes.", "content": "Membrane preparations obtained from a stabilized L-form of Streptococcus pyogenes are incapable of synthesizing peptidoglycan from uridine-5'-diphospho-N-acetyl-D-muramyl-L-Ala-D-iso-Glu-L-Lys-D-Ala-D-Ala and uridine-5'-diphospho-N-acetyl-D-glucosamine, in contrast with similar preparations from the parental streptococcus. Furthermore, 50-fold higher levels of lipid intermediates which serve as membrane-bound substrates for peptidoglycan synthesis are synthesized in reaction mixtures containing streptococcal membranes than with similar preparations from the L-form. These observations suggest that the inability of this stabilized L-form to form a cell wall in vivo lies, at least in part, in its failure to synthesize significant quantities of the lipid substrates for peptidoglycan synthesis.", "contents": "Defective synthesis of lipid intermediates for peptidoglycan formation in a stabilized L-form of Streptococcus pyogenes. Membrane preparations obtained from a stabilized L-form of Streptococcus pyogenes are incapable of synthesizing peptidoglycan from uridine-5'-diphospho-N-acetyl-D-muramyl-L-Ala-D-iso-Glu-L-Lys-D-Ala-D-Ala and uridine-5'-diphospho-N-acetyl-D-glucosamine, in contrast with similar preparations from the parental streptococcus. Furthermore, 50-fold higher levels of lipid intermediates which serve as membrane-bound substrates for peptidoglycan synthesis are synthesized in reaction mixtures containing streptococcal membranes than with similar preparations from the L-form. These observations suggest that the inability of this stabilized L-form to form a cell wall in vivo lies, at least in part, in its failure to synthesize significant quantities of the lipid substrates for peptidoglycan synthesis."}
{"id": "PMID:4427", "title": "Protonmotive force as the source of energy for adenosine 5'-triphosphate synthesis in Escherichia coli.", "content": "Net synthesis of adenosine 5'-triphosphate (ATP) in energy-depleted cells of Escherichia coli was observed when an inwardly directed protonmotive force was artificially imposed. In wild-type cells, ATP synthesis occurred whether the protonmotive force was dominated by the membrane potential (negative inside) or the pH gradient (alkaline inside). Formation of ATP did not occur unless the protonmotive force exceeded a value of 200 mV. Under these conditions, no ATP synthesis was found when cells were exposed to an inhibitor of the membrane-bound Ca2+- and Mg2+- stimulated adenosine triphosphatase (EC 3.6.1.3), dicyclohexylcarbodiimide, or to a proton conductor, carbonylcyanide-p-trifluoromethoxyphenyl-hydrazone. Adenosine triphosphatase-negative mutants failed to show ATP synthesis in response to either a membrane potential or a pH gradient. ATP synthesis driven by a protonmotive force was observed in a cytochrome-deficient mutant. These observations are consistent with the chemiosmotic hypothesis of Mitchell (1961, 1966, 1974).", "contents": "Protonmotive force as the source of energy for adenosine 5'-triphosphate synthesis in Escherichia coli. Net synthesis of adenosine 5'-triphosphate (ATP) in energy-depleted cells of Escherichia coli was observed when an inwardly directed protonmotive force was artificially imposed. In wild-type cells, ATP synthesis occurred whether the protonmotive force was dominated by the membrane potential (negative inside) or the pH gradient (alkaline inside). Formation of ATP did not occur unless the protonmotive force exceeded a value of 200 mV. Under these conditions, no ATP synthesis was found when cells were exposed to an inhibitor of the membrane-bound Ca2+- and Mg2+- stimulated adenosine triphosphatase (EC 3.6.1.3), dicyclohexylcarbodiimide, or to a proton conductor, carbonylcyanide-p-trifluoromethoxyphenyl-hydrazone. Adenosine triphosphatase-negative mutants failed to show ATP synthesis in response to either a membrane potential or a pH gradient. ATP synthesis driven by a protonmotive force was observed in a cytochrome-deficient mutant. These observations are consistent with the chemiosmotic hypothesis of Mitchell (1961, 1966, 1974)."}
{"id": "PMID:4428", "title": "Inhibition of dimethyl ether and methane oxidation in Methylococcus capsulatus and Methylosinus trichosporium.", "content": "Metal-chelating or -binding agents inhibited the oxidation of dimethyl ether and methane, but not methanol, by cell suspensions of Methylococcus capsulatus and Methylosinus trichosporium. Evidence suggests that the involvement of metal-containing enzymatic systems in the initial step of oxidation of dimethyl ether and methane.", "contents": "Inhibition of dimethyl ether and methane oxidation in Methylococcus capsulatus and Methylosinus trichosporium. Metal-chelating or -binding agents inhibited the oxidation of dimethyl ether and methane, but not methanol, by cell suspensions of Methylococcus capsulatus and Methylosinus trichosporium. Evidence suggests that the involvement of metal-containing enzymatic systems in the initial step of oxidation of dimethyl ether and methane."}
{"id": "PMID:4429", "title": "Effect of colicin K on a membrane-associated, energy-linked function.", "content": "The purpose of this work was in investigate the capability of cell extracts of Escherichia coli and E. coli treated with colicin K to catalyze the following energy-dependent reverse transhydrogenase reaction: NADP + NADH + ATP in equilibrium NADPH + NAD +ADP + Pi. Under anaerobic conditions this reaction requires the presence of a specific portion of the electron transport chain, a functional energy coupling system, including an adenosine triphosphatase, enzyme, and ATP as energy source. The ATP-linked reaction was partially inhibited in French press extracts of E. coli K-12 C600 cells that had been pretreated with colicin K but not in extracts from similarly treated cells of a colicin-tolerant mutant. Ultracentrifugation of extracts yielded particulate fractions competent in catalyzing the reaction; this reaction is substantially inhibited in fractions from colicin-treated cells. The extent of inhibition increased with increasing concentration of colicin. Supernatants also supported ATP-linked formation of NADPH, but this reaction was insensitive to the colicin effect. A comparison between the requirement of the reaction in supernatant and particulate fractions suggests that the reaction in the supernatant is different from the one inhibited by colicin. The ATP-hydrolyzing ability of particulate fractions from the control or treated bacteria was identical. Likewise, the electron transport chain was not affected by colicin treatment, as evidenced from lack of effect on NADH oxidase, succinic dehydrogenase, and NADPH-NAD transhydrogenase. It is concluded that colicin K interferes with the coupling of ATP the utilization of the intermediate for the ATP-linked transdehydrogenase reaction.", "contents": "Effect of colicin K on a membrane-associated, energy-linked function. The purpose of this work was in investigate the capability of cell extracts of Escherichia coli and E. coli treated with colicin K to catalyze the following energy-dependent reverse transhydrogenase reaction: NADP + NADH + ATP in equilibrium NADPH + NAD +ADP + Pi. Under anaerobic conditions this reaction requires the presence of a specific portion of the electron transport chain, a functional energy coupling system, including an adenosine triphosphatase, enzyme, and ATP as energy source. The ATP-linked reaction was partially inhibited in French press extracts of E. coli K-12 C600 cells that had been pretreated with colicin K but not in extracts from similarly treated cells of a colicin-tolerant mutant. Ultracentrifugation of extracts yielded particulate fractions competent in catalyzing the reaction; this reaction is substantially inhibited in fractions from colicin-treated cells. The extent of inhibition increased with increasing concentration of colicin. Supernatants also supported ATP-linked formation of NADPH, but this reaction was insensitive to the colicin effect. A comparison between the requirement of the reaction in supernatant and particulate fractions suggests that the reaction in the supernatant is different from the one inhibited by colicin. The ATP-hydrolyzing ability of particulate fractions from the control or treated bacteria was identical. Likewise, the electron transport chain was not affected by colicin treatment, as evidenced from lack of effect on NADH oxidase, succinic dehydrogenase, and NADPH-NAD transhydrogenase. It is concluded that colicin K interferes with the coupling of ATP the utilization of the intermediate for the ATP-linked transdehydrogenase reaction."}
{"id": "PMID:4430", "title": "Ribonucleic acid synthesized in meiotic cells of Saccharomyces cerevisiae: effect of culture medium pH.", "content": "Pulse-labeled ribonucleic acid (RNA) was extracted from polysomes of sporulating cells of Saccharomyces cerevisiae and characterized in sucrose gradients and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Transfer RNA, ribosomal RNA, and heterodisperse RNA, presumed to be messenger RNA, were synthesized during a 20-min pulse at T4 and T6 when labeling was performed in sporulation medium adjusted to pH 6.0. Furthermore, ribosomal RNA was processed into functional ribosomes during the pulse. The specific activity of pulse-labeled RNA of cells labeled in sporulation medium where the pH was unadjusted at T4 (pH 7.8) and T9 (pH 8.6) was 20- to 50-fold lower than RNA from cells labeled at pH 6.0. The low specific activity resulted from a 50-fold reduction in uptake of labeled precursors when the medium pH was greater than 7.2. However, heterodisperse RNA ranging from 4-17S in size and transfer RNA were synthesized during the pulse at T4 (pH 7.8),but the low specific activity of ribosomal RNA prevented a thorough analysis of its synthesis. Cellular impermeability at T9 (pH 8.6) resulted in minimal uptake of label, and an analysis of pulse-labeled transcripts was impossible. A comparison of the percantage of polysomal material indicate, however, that these cells were at least as active in translation as cells pulse-labeled at pH 6.0.", "contents": "Ribonucleic acid synthesized in meiotic cells of Saccharomyces cerevisiae: effect of culture medium pH. Pulse-labeled ribonucleic acid (RNA) was extracted from polysomes of sporulating cells of Saccharomyces cerevisiae and characterized in sucrose gradients and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Transfer RNA, ribosomal RNA, and heterodisperse RNA, presumed to be messenger RNA, were synthesized during a 20-min pulse at T4 and T6 when labeling was performed in sporulation medium adjusted to pH 6.0. Furthermore, ribosomal RNA was processed into functional ribosomes during the pulse. The specific activity of pulse-labeled RNA of cells labeled in sporulation medium where the pH was unadjusted at T4 (pH 7.8) and T9 (pH 8.6) was 20- to 50-fold lower than RNA from cells labeled at pH 6.0. The low specific activity resulted from a 50-fold reduction in uptake of labeled precursors when the medium pH was greater than 7.2. However, heterodisperse RNA ranging from 4-17S in size and transfer RNA were synthesized during the pulse at T4 (pH 7.8),but the low specific activity of ribosomal RNA prevented a thorough analysis of its synthesis. Cellular impermeability at T9 (pH 8.6) resulted in minimal uptake of label, and an analysis of pulse-labeled transcripts was impossible. A comparison of the percantage of polysomal material indicate, however, that these cells were at least as active in translation as cells pulse-labeled at pH 6.0."}
{"id": "PMID:4431", "title": "An enzyme common to histidine and aromatic amino acid biosynthesis in Bacillus subtilis.", "content": "Two transaminases exist for tyrosine and phenylalanine synthesis in Bacillus subtilis. One enzyme is also responsible for the transamination of imidazole acetol phosphate to histidinol phosphate, an obligatory reaction in the synthesis of histidine. The gene involved in the synthesis of this enzyme lies in the middle of a cluster of genes, all of which are concerned with the synthesis of the aromatic amino acids. The other gene has not yet been mapped. Mutants have been isolated that lack one or the other enzyme activity. These mutants are prototrophic for tyrosine and phenylalanine. However, both classes of mutants are more sensitive than the wild-type strain to the phenylalanine analogue, fluorophenylalanine, suggesting that each of these mutants synthesizes less phenylalanine than does the wild-type strain. The two enzymes can be separated from one another by ion-exchange chromatography and glycerol-gradient centrifugation. The significance of the observation that an enzyme of histidine synthesis also plays a role in the synthesis of the aromatic acids is considered in light of cross-pathways regulation between the two pathways.", "contents": "An enzyme common to histidine and aromatic amino acid biosynthesis in Bacillus subtilis. Two transaminases exist for tyrosine and phenylalanine synthesis in Bacillus subtilis. One enzyme is also responsible for the transamination of imidazole acetol phosphate to histidinol phosphate, an obligatory reaction in the synthesis of histidine. The gene involved in the synthesis of this enzyme lies in the middle of a cluster of genes, all of which are concerned with the synthesis of the aromatic amino acids. The other gene has not yet been mapped. Mutants have been isolated that lack one or the other enzyme activity. These mutants are prototrophic for tyrosine and phenylalanine. However, both classes of mutants are more sensitive than the wild-type strain to the phenylalanine analogue, fluorophenylalanine, suggesting that each of these mutants synthesizes less phenylalanine than does the wild-type strain. The two enzymes can be separated from one another by ion-exchange chromatography and glycerol-gradient centrifugation. The significance of the observation that an enzyme of histidine synthesis also plays a role in the synthesis of the aromatic acids is considered in light of cross-pathways regulation between the two pathways."}
{"id": "PMID:4432", "title": "Regulation of Chorismate mutase-prephenate dehydratase and prephenate dehydrogenase from alcaligenes eutrophus.", "content": "Highly purified enzymes from Alcaligenes eutrophus H 16 were used for kinetic studies. Chorismate mutase was feedback inhibited by phenylalanine. In the absence of the inhibitor, the double-reciprocal plot was linear, yielding a Km for chorismate of 0.2 mM. When phenylalanine was present, a pronounced deviation from the Michaelis-Menten hyperbola occurred. The Hill coefficient (n) was 1.7, and Hill plots of velocity versus inhibitor concentrations resulted in a value of n' = 2.3, indicating positive cooperativity. Chorismate mutase was also inhibited by prephenate, which caused downward double-reciprocal plots and a Hill coefficient of n = 0.7, evidence for negative cooperativity. The pH optimum of chorismate mutase ranged from 7.8 to 8.2; its temperature optimum was 47 C. Prephenate dehydratase was competitively inhibited by phenylalanine and activated by tyrosine. Tyrosine stimulated its activity up to 10-fold and decreased the Km for prephenate, which was 0.67 mM without effectors. Tryptophan inhibited the enzyme competitively. Its inhibition constant (Ki = 23 muM) was almost 10-fold higher than that determined for phenylalanine (Ki = 2.6 muM). The pH optimum of prephenate dehydratase was pH 5.7; the temperature optimum was 48 C. Prephenate dehydrogenase was feedback inhibited by tyrosine. Inhibition was competitive with prephenate (Ki = 0.06 mM) and noncompetitive with nicotinamide adenine dinucleotide. The enzyme was further subject to product inhibition by p-hydroxyphenylpyruvate (Ki = 0.13 mM). Its Km for prephenate was 0.045 mM, and that for nicotinamide adenine dinucleotide was 0.14 mM. The pH optimum ranged between 7.0 and 7.6; the temperature optimum was 38 C. It is shown how the sensitive regulation of the entire enzyme system leads to a well-balanced amino acid production.", "contents": "Regulation of Chorismate mutase-prephenate dehydratase and prephenate dehydrogenase from alcaligenes eutrophus. Highly purified enzymes from Alcaligenes eutrophus H 16 were used for kinetic studies. Chorismate mutase was feedback inhibited by phenylalanine. In the absence of the inhibitor, the double-reciprocal plot was linear, yielding a Km for chorismate of 0.2 mM. When phenylalanine was present, a pronounced deviation from the Michaelis-Menten hyperbola occurred. The Hill coefficient (n) was 1.7, and Hill plots of velocity versus inhibitor concentrations resulted in a value of n' = 2.3, indicating positive cooperativity. Chorismate mutase was also inhibited by prephenate, which caused downward double-reciprocal plots and a Hill coefficient of n = 0.7, evidence for negative cooperativity. The pH optimum of chorismate mutase ranged from 7.8 to 8.2; its temperature optimum was 47 C. Prephenate dehydratase was competitively inhibited by phenylalanine and activated by tyrosine. Tyrosine stimulated its activity up to 10-fold and decreased the Km for prephenate, which was 0.67 mM without effectors. Tryptophan inhibited the enzyme competitively. Its inhibition constant (Ki = 23 muM) was almost 10-fold higher than that determined for phenylalanine (Ki = 2.6 muM). The pH optimum of prephenate dehydratase was pH 5.7; the temperature optimum was 48 C. Prephenate dehydrogenase was feedback inhibited by tyrosine. Inhibition was competitive with prephenate (Ki = 0.06 mM) and noncompetitive with nicotinamide adenine dinucleotide. The enzyme was further subject to product inhibition by p-hydroxyphenylpyruvate (Ki = 0.13 mM). Its Km for prephenate was 0.045 mM, and that for nicotinamide adenine dinucleotide was 0.14 mM. The pH optimum ranged between 7.0 and 7.6; the temperature optimum was 38 C. It is shown how the sensitive regulation of the entire enzyme system leads to a well-balanced amino acid production."}
{"id": "PMID:4433", "title": "Role of deoxyribonucleic acid ligase in a doxyribonucleic acid membrane fraction extracted from pneumococci.", "content": "Deoxyribonucleic acid (DNA) ligase has been detected in a DNA membrane fraction extracted from Pneumococcus. The specific activity of the enzyme in this fraction is 10-fold greater than in the remaining cell extract. It remains firmly bound (with other enzymes) to the complex after a purification procedure in which a considerable percentage of the macromolecules are dissociated. The ligase acts in two ways in the DNA membrane fraction in vitro. One, it catalyzes the linkage of small-molecular-weight pieces of newly synthesized DNA into heavier-molecular-weight DNA strands as shown by others (M Gellert, 1976; R. Okazaki, A. Sugino, S. Hirose, T. Okazaki, Y. Imae, R. Kainuma-Kuroda, T. Ogawa, M. Arisawa, and Y. Kurosowa, 1973; B. Olivera and I. Lehman, 14; and A. Sugino, S. Hirose, and R. Okazaki, 1972) and, two, it protects DNA from degradation by deoxyribonucleases. This latter effect is due to a competition between the ability of the nucleases to degrade DNA and the ability of DNA ligase to seal the nicks produced by these degradative enzymes. The ligase acts cooperatively with other enzymes in the DNA membrane fraction to synthesize DNA.", "contents": "Role of deoxyribonucleic acid ligase in a doxyribonucleic acid membrane fraction extracted from pneumococci. Deoxyribonucleic acid (DNA) ligase has been detected in a DNA membrane fraction extracted from Pneumococcus. The specific activity of the enzyme in this fraction is 10-fold greater than in the remaining cell extract. It remains firmly bound (with other enzymes) to the complex after a purification procedure in which a considerable percentage of the macromolecules are dissociated. The ligase acts in two ways in the DNA membrane fraction in vitro. One, it catalyzes the linkage of small-molecular-weight pieces of newly synthesized DNA into heavier-molecular-weight DNA strands as shown by others (M Gellert, 1976; R. Okazaki, A. Sugino, S. Hirose, T. Okazaki, Y. Imae, R. Kainuma-Kuroda, T. Ogawa, M. Arisawa, and Y. Kurosowa, 1973; B. Olivera and I. Lehman, 14; and A. Sugino, S. Hirose, and R. Okazaki, 1972) and, two, it protects DNA from degradation by deoxyribonucleases. This latter effect is due to a competition between the ability of the nucleases to degrade DNA and the ability of DNA ligase to seal the nicks produced by these degradative enzymes. The ligase acts cooperatively with other enzymes in the DNA membrane fraction to synthesize DNA."}
{"id": "PMID:4434", "title": "Relationship between hemagglutinin and sialidase from Clostridium perfringens CN3870: chromatographic characterization of the biologically active proteins.", "content": "Biochemical characterization of hemagglutinin and sialidase activities from Clostridium perfringens strain CN3870 revealed that this strain produced three sialidase enzymes that were separable to gel filtration, ion exchange chromatography, and polyacrylamide gel electrophoresis. The molecular weights of sialidase I, II, and III activities were 310,000 +/- 10,000, 105,000 +/- 4,000 and 64,000 +/- 2,000, respectively, the first figure being an approximate value only.", "contents": "Relationship between hemagglutinin and sialidase from Clostridium perfringens CN3870: chromatographic characterization of the biologically active proteins. Biochemical characterization of hemagglutinin and sialidase activities from Clostridium perfringens strain CN3870 revealed that this strain produced three sialidase enzymes that were separable to gel filtration, ion exchange chromatography, and polyacrylamide gel electrophoresis. The molecular weights of sialidase I, II, and III activities were 310,000 +/- 10,000, 105,000 +/- 4,000 and 64,000 +/- 2,000, respectively, the first figure being an approximate value only."}
{"id": "PMID:4435", "title": "Relationship between hemagglutinin and sialidase from Clostridium perfringens CN3870: gel filtration of mutant and reverant activities.", "content": "Gel filtration of supernatant fluids, from the wild-type Clostridium perfringens, strain CN3870, and several of the mutants and reverants derived from this strain, showed that these mutants failed to product detectable amounts of still produced sialidase III activity. The reverants tested had regained the ability to produce approximately wild-type levels of the I and II forms of both activities. These results showthat there is a direct relationship between the production of the I form and hemagglutinin and sialidase activities and the production of the II form of these biologically active proteins. Models that explain the genetic basis for these results are discussed.", "contents": "Relationship between hemagglutinin and sialidase from Clostridium perfringens CN3870: gel filtration of mutant and reverant activities. Gel filtration of supernatant fluids, from the wild-type Clostridium perfringens, strain CN3870, and several of the mutants and reverants derived from this strain, showed that these mutants failed to product detectable amounts of still produced sialidase III activity. The reverants tested had regained the ability to produce approximately wild-type levels of the I and II forms of both activities. These results showthat there is a direct relationship between the production of the I form and hemagglutinin and sialidase activities and the production of the II form of these biologically active proteins. Models that explain the genetic basis for these results are discussed."}
{"id": "PMID:4436", "title": "Development of Microbodies in the yeast Kloeckera growing on methanol.", "content": "A number of microbodies appear regularly in methanol-grown yeast cells, but rarely in ethanol- or glucose-grown cells. When one of representative methanol-utilizing yeasts, Kloeckera sp.no. 2201 (also known as Candida bodinii), was cultured on glucose and then transferred into a methanol medium, microbodies of small size could be observed in 2-h old cells. The number of microbodies per sectioned cell reached five to six after 4 h of cultivation. Though the number of microbodies did not change during prolonged cultivation, their size became larger with the passage of cultivation time. The activities of catalase and alcohol oxidase were confirmed in the particulate fractions throughout the cultivation period, whereas the activities of formaldehyde dehydrogenase and formate dehydrogenase were not detected in the particles. The activity of isocitrate lyase was detected in the particulate fractions only at the early growth phase.", "contents": "Development of Microbodies in the yeast Kloeckera growing on methanol. A number of microbodies appear regularly in methanol-grown yeast cells, but rarely in ethanol- or glucose-grown cells. When one of representative methanol-utilizing yeasts, Kloeckera sp.no. 2201 (also known as Candida bodinii), was cultured on glucose and then transferred into a methanol medium, microbodies of small size could be observed in 2-h old cells. The number of microbodies per sectioned cell reached five to six after 4 h of cultivation. Though the number of microbodies did not change during prolonged cultivation, their size became larger with the passage of cultivation time. The activities of catalase and alcohol oxidase were confirmed in the particulate fractions throughout the cultivation period, whereas the activities of formaldehyde dehydrogenase and formate dehydrogenase were not detected in the particles. The activity of isocitrate lyase was detected in the particulate fractions only at the early growth phase."}
{"id": "PMID:4437", "title": "Phosphatase of Chlamydomonas reinhardi: biochemical and cytochemical approach with specific mutants.", "content": "The unicellular alga Chlamydomonas reinhardi produces two constitutive acid phosphatases and three depressible phosphatases (a neutral and two alkaline ones) that can utilize napthyl phosphate as a substrate. Specific mutants depressible phosphatase were used to investigate biochemical properties and the cytochemical localization of these enzymes. The two constitutive phosphatases show similar pH optima (about 5.0) and Km values (2 x 10(-3) to 3.3 x 10(-3) M) but differ in their heat sensitivity and affinity for glycerophosphate.", "contents": "Phosphatase of Chlamydomonas reinhardi: biochemical and cytochemical approach with specific mutants. The unicellular alga Chlamydomonas reinhardi produces two constitutive acid phosphatases and three depressible phosphatases (a neutral and two alkaline ones) that can utilize napthyl phosphate as a substrate. Specific mutants depressible phosphatase were used to investigate biochemical properties and the cytochemical localization of these enzymes. The two constitutive phosphatases show similar pH optima (about 5.0) and Km values (2 x 10(-3) to 3.3 x 10(-3) M) but differ in their heat sensitivity and affinity for glycerophosphate."}
{"id": "PMID:4438", "title": "Autolysis of Neisseria gonorrhoeae.", "content": "Autolysis of Neisseria gonorrhoeae was studied under different conditions. It was found that low pH and temperature, as well as the presence of divalent cations, spermine, sucrose, and polyvinylpyrrolidone, stabilized nongrowing gonococci. Ethylenediaminetetraacetic acid alone promoted lysis, whereas lysozyme had only a limited additive effect. The autolytic behavior of gonococci appears to be connected with their prolonged cell division process. The relative dependence on the outer membrane and the peptidoglycan layer for the mechanical stability of gonococci is discussed.", "contents": "Autolysis of Neisseria gonorrhoeae. Autolysis of Neisseria gonorrhoeae was studied under different conditions. It was found that low pH and temperature, as well as the presence of divalent cations, spermine, sucrose, and polyvinylpyrrolidone, stabilized nongrowing gonococci. Ethylenediaminetetraacetic acid alone promoted lysis, whereas lysozyme had only a limited additive effect. The autolytic behavior of gonococci appears to be connected with their prolonged cell division process. The relative dependence on the outer membrane and the peptidoglycan layer for the mechanical stability of gonococci is discussed."}
{"id": "PMID:4439", "title": "Glucose-6-phosphate dehydrogenase. Purification and partial characterization.", "content": "Glucose-6-phosphate dehydrogenase has been purified 1000-fold from pig liver. This enzyme exists as an active dimer of molecular weight 133,000 and an inactive monomer of molecular weight 67,500. The pH of maximum activity is 8.5 and the ionic strength maximum is 0.1 to 0.5 M. Glucose-6-phosphate dehydrogenase is highly specific for NADP+ and glucose 6-phosphate. Apparent Km values of 3.6 muM and 5.4 muM were obtained for glucose 6-phosphate and NADP+. This enzyme is located almost entirely within the soluble portion of the cellular cytoplasm.", "contents": "Glucose-6-phosphate dehydrogenase. Purification and partial characterization. Glucose-6-phosphate dehydrogenase has been purified 1000-fold from pig liver. This enzyme exists as an active dimer of molecular weight 133,000 and an inactive monomer of molecular weight 67,500. The pH of maximum activity is 8.5 and the ionic strength maximum is 0.1 to 0.5 M. Glucose-6-phosphate dehydrogenase is highly specific for NADP+ and glucose 6-phosphate. Apparent Km values of 3.6 muM and 5.4 muM were obtained for glucose 6-phosphate and NADP+. This enzyme is located almost entirely within the soluble portion of the cellular cytoplasm."}
{"id": "PMID:4440", "title": "A kinetic study of glucose-6-phosphate dehydrogenase.", "content": "The steady state kinetics of pig liver glucose-6-phosphate dehydrogenase is consistent with an ordered, sequential mechanism in which NADP is bound first and NADPH released last. Kia is 9.0 muM, Ka is 4.8 muM, and Kb is 36 muM. Glucosamine 6-phosphate, a substrate analogue and competitive inhibitor, is used to help rule out a possible random mechanism. ADP is seen to form a complex with the free form of the enzyme whereas ATP forms a complex with both the free and E-NADP forms of the enzyme. The KI for the E-ADP complex is 1.9 mM, while the Ki values for the E-ATP and E-NADP-ATP complexes are 7.2 and 4.5 mM, respectively.", "contents": "A kinetic study of glucose-6-phosphate dehydrogenase. The steady state kinetics of pig liver glucose-6-phosphate dehydrogenase is consistent with an ordered, sequential mechanism in which NADP is bound first and NADPH released last. Kia is 9.0 muM, Ka is 4.8 muM, and Kb is 36 muM. Glucosamine 6-phosphate, a substrate analogue and competitive inhibitor, is used to help rule out a possible random mechanism. ADP is seen to form a complex with the free form of the enzyme whereas ATP forms a complex with both the free and E-NADP forms of the enzyme. The KI for the E-ADP complex is 1.9 mM, while the Ki values for the E-ATP and E-NADP-ATP complexes are 7.2 and 4.5 mM, respectively."}
{"id": "PMID:4441", "title": "alpha-Aminomethylglutarate, a beta-amino analog of glutamate that interacts with glutamine synthetase and the enzymes that catalyze glutathione synthesis.", "content": "The glutamate analog, alpha-aminomethylglutaric acid, was synthetized by Michael addition of ammonia to 2-methylene glutaronitrile followed by hydrolysis of the intermediate alpha-aminomethylglutaryl nitrile; the analog cyclizes readily on heating to 2-piperidone-5-carboxylic acid. Sheep brain glutamine synthetase utilizes one isomer of DL-alpha-aminomethylglutarate at about 10% of the rate with L-glutamate. gamma-Glutamylcysteine synthetase uses both isomers of DL-alpha-aminomethylglutarate, preferentially acting on the same isomer used by glutamine synthetase. gamma-(alpha-Aminomethyl)glutaryl-alpha-aminobutyrate, prepared enzymatically with gamma-glutamylcysteine synthetase, was found to be a substrate and an inhibitor of glutathione synthetase. alpha-Aminomethylglutarate does not inhibit gamma-glutamyl cyclotransferase and gamma-glutamyl transpeptidase appreciably. When alpha-aminomethylglutarate was administered to mice, there were substantial decreases in the levels of glutamine, glutathione, glutamate, and glycine in the kidney, and of glutamine and glutamate in the liver, indicating that this glutamate analog is effective as an inhibitor of glutamine and glutathione synthesis in vivo, and suggesting that it may also inhibit other enzymes.", "contents": "alpha-Aminomethylglutarate, a beta-amino analog of glutamate that interacts with glutamine synthetase and the enzymes that catalyze glutathione synthesis. The glutamate analog, alpha-aminomethylglutaric acid, was synthetized by Michael addition of ammonia to 2-methylene glutaronitrile followed by hydrolysis of the intermediate alpha-aminomethylglutaryl nitrile; the analog cyclizes readily on heating to 2-piperidone-5-carboxylic acid. Sheep brain glutamine synthetase utilizes one isomer of DL-alpha-aminomethylglutarate at about 10% of the rate with L-glutamate. gamma-Glutamylcysteine synthetase uses both isomers of DL-alpha-aminomethylglutarate, preferentially acting on the same isomer used by glutamine synthetase. gamma-(alpha-Aminomethyl)glutaryl-alpha-aminobutyrate, prepared enzymatically with gamma-glutamylcysteine synthetase, was found to be a substrate and an inhibitor of glutathione synthetase. alpha-Aminomethylglutarate does not inhibit gamma-glutamyl cyclotransferase and gamma-glutamyl transpeptidase appreciably. When alpha-aminomethylglutarate was administered to mice, there were substantial decreases in the levels of glutamine, glutathione, glutamate, and glycine in the kidney, and of glutamine and glutamate in the liver, indicating that this glutamate analog is effective as an inhibitor of glutamine and glutathione synthesis in vivo, and suggesting that it may also inhibit other enzymes."}
{"id": "PMID:4442", "title": "Studies of human kidney gamma-glutamyl transpeptidase. Purification and structural, kinetic and immunological properties.", "content": "gamma-Glutamyl transpeptidase, present in various mammalian tissues, transfers the gamma-glutamyl moiety of glutathione to a variety of acceptor amino acids and peptides. This enzyme has been purified from human kidney cortex about 740-fold to a specific activity of 200 units/mg of protein. The purification steps involved incubation of the homogenate at 37 degrees followed by centrifugation and extraction of the sediment with 0.1 M Tris-HCl buffer, pH 8.0, containing 1% sodium deoxycholate; batchwise absorption on DEAE-cellulose; DEAE-cellulose (DE52) column chromatography; Sephadex G-200 gel filtration; and affinity chromatography using concanavalin A insolubilized on beaded Agarose. Detergents were used throughout the purification of the enzyme. The purified enzyme separated into three protein bands, all of which had enzyme activity, on polyacrylamide disc electrophoresis in the presence of Triton X-100. The enzyme has an apparent molecular weight of about 90,000 as shown by Sephadex G-200 gel filtration, and appears to be a tetramer with subunits of molecular weights of about 21,000. The Km for gamma-glutamyl transpeptidase using the artificial substrate, gamma-glutamyl-p-nitroanilide, with glycylglycine as the acceptor amino acid was found to be about 0.8 mM. The optimum pH for the enzyme activity is 8.2 and the isoelectric point is 4.5. Both GSH and GSSG competitively inhibited the activity of gamma-glutamyl transpeptidase when gamma-glutamyl-p-nitroanilide was used as the substrate. Treatment of the purified enzyme with papain has no effect on the enzyme activity or mobility on polyacrylamide disc electrophoresis. The purified gamma-glutamyl transpeptidase had no phosphate-independent glutaminase activity. The ratio of gamma-glutamyl transpeptidase to phosphate-independent glutaminase changed significantly through the initial steps of gamma-glutamyl transpeptidase purification. These studies indicate that the transpeptidase and phosphate-independent glutaminase activities are not exhibited by the same protein in human kidney.", "contents": "Studies of human kidney gamma-glutamyl transpeptidase. Purification and structural, kinetic and immunological properties. gamma-Glutamyl transpeptidase, present in various mammalian tissues, transfers the gamma-glutamyl moiety of glutathione to a variety of acceptor amino acids and peptides. This enzyme has been purified from human kidney cortex about 740-fold to a specific activity of 200 units/mg of protein. The purification steps involved incubation of the homogenate at 37 degrees followed by centrifugation and extraction of the sediment with 0.1 M Tris-HCl buffer, pH 8.0, containing 1% sodium deoxycholate; batchwise absorption on DEAE-cellulose; DEAE-cellulose (DE52) column chromatography; Sephadex G-200 gel filtration; and affinity chromatography using concanavalin A insolubilized on beaded Agarose. Detergents were used throughout the purification of the enzyme. The purified enzyme separated into three protein bands, all of which had enzyme activity, on polyacrylamide disc electrophoresis in the presence of Triton X-100. The enzyme has an apparent molecular weight of about 90,000 as shown by Sephadex G-200 gel filtration, and appears to be a tetramer with subunits of molecular weights of about 21,000. The Km for gamma-glutamyl transpeptidase using the artificial substrate, gamma-glutamyl-p-nitroanilide, with glycylglycine as the acceptor amino acid was found to be about 0.8 mM. The optimum pH for the enzyme activity is 8.2 and the isoelectric point is 4.5. Both GSH and GSSG competitively inhibited the activity of gamma-glutamyl transpeptidase when gamma-glutamyl-p-nitroanilide was used as the substrate. Treatment of the purified enzyme with papain has no effect on the enzyme activity or mobility on polyacrylamide disc electrophoresis. The purified gamma-glutamyl transpeptidase had no phosphate-independent glutaminase activity. The ratio of gamma-glutamyl transpeptidase to phosphate-independent glutaminase changed significantly through the initial steps of gamma-glutamyl transpeptidase purification. These studies indicate that the transpeptidase and phosphate-independent glutaminase activities are not exhibited by the same protein in human kidney."}
{"id": "PMID:4443", "title": "Kinetics of the hemerythrin-oxygen interaction.", "content": "The kinetics of the reaction of Golfingia gouldii hemerythrin with O2 have been studied by stopped flow spectrophotometry. For the second order oxygenation process, k1 = 7.4 X 10(6) M-1 s-1, deltaH1++ = 8.2 kcal-mol-1 and deltaS1++ = +1 e.u. at 25 degrees, pH 8.2, and I = 0.015 M. The rate constant is unchanged when protein concentration is varied from 3 to 25 muM, the ionic strength is increased to 0.07 M, and the pH moved to 6.8. The deoxygenation of oxyhemerythrin is studied with stopped flow by scavenging liberated O2 with S2O4(2-). For the first order dissociation, k-1 = 51 s-1, deltaH-1++ = 20.6 kcal-mol-1 and deltaS-1++ = +19 e.u. at 25 degrees, pH 8.2, and I = 0.015 M. The value of k-1 is independent of [protein] = 50 to 200 muM, [S2O4(2-)] = 5 to 100 mM I = 0.015 to 0.30 M and pH 6.8 to 9.0. Using myoglobin instead of S2O4(2-) as scavenger gives similar results. Combination of activation parameters for the oxygenation and deoxygenation processes gives K1 = 1.5 X 10(5) M-1, deltaH = -12.4 kcal-mol-1, and deltaS = -18 e.u., values in good agreement with independent thermodynamic data. Perchlorate ion (0.05 M) enhances k-1 about 3-fold and hardly effects k1. There is no sign of other than a single reaction in either direction, and octameric hemerythrin apparently behaves kinetically as eight single units.", "contents": "Kinetics of the hemerythrin-oxygen interaction. The kinetics of the reaction of Golfingia gouldii hemerythrin with O2 have been studied by stopped flow spectrophotometry. For the second order oxygenation process, k1 = 7.4 X 10(6) M-1 s-1, deltaH1++ = 8.2 kcal-mol-1 and deltaS1++ = +1 e.u. at 25 degrees, pH 8.2, and I = 0.015 M. The rate constant is unchanged when protein concentration is varied from 3 to 25 muM, the ionic strength is increased to 0.07 M, and the pH moved to 6.8. The deoxygenation of oxyhemerythrin is studied with stopped flow by scavenging liberated O2 with S2O4(2-). For the first order dissociation, k-1 = 51 s-1, deltaH-1++ = 20.6 kcal-mol-1 and deltaS-1++ = +19 e.u. at 25 degrees, pH 8.2, and I = 0.015 M. The value of k-1 is independent of [protein] = 50 to 200 muM, [S2O4(2-)] = 5 to 100 mM I = 0.015 to 0.30 M and pH 6.8 to 9.0. Using myoglobin instead of S2O4(2-) as scavenger gives similar results. Combination of activation parameters for the oxygenation and deoxygenation processes gives K1 = 1.5 X 10(5) M-1, deltaH = -12.4 kcal-mol-1, and deltaS = -18 e.u., values in good agreement with independent thermodynamic data. Perchlorate ion (0.05 M) enhances k-1 about 3-fold and hardly effects k1. There is no sign of other than a single reaction in either direction, and octameric hemerythrin apparently behaves kinetically as eight single units."}
{"id": "PMID:4444", "title": "Guanylate cyclase and cyclic guanosine 3':5'-monophosphate phosphodiesterase activities and cyclic guanosine 3':5'-monophosphate levels in normal and transformed fibroblasts in culture.", "content": "To investigate the role of guanosine 3':5'-monophosphate (cyclic GMP) in cultured cells we have measured guanylate cyclase and cyclic GMP phosphodiesterase activities and cyclic GMP levels in normal and transformed fibroblastic cells. Guanylate cyclase activity is found almost exclusively in the particulate fraction of normal rat kidney (NRK) and BALB 3T3 cells. Enzyme activity is stimulated 3- to 10-fold by treatment with the detergent Lubrol PX. However, enhancement of guanylate cyclase by fibroblast growth factor could not be demonstrated under a variety of assay conditions. In both NRK and BALB 3T3 cells guanylate cyclase activity is low during logarithmic growth and increases as the cells crowd together and growth slows. Guanylate cyclase activity is undetectable in homogenates of NRK cells transformed by the Kirsten sarcoma virus (KNRK cells) either in the presence or absence of Lubrol PX. Guanylate cyclase activity is also greatly decreased in NRK cells transformed by Moloney, Schmidt-Ruppin, or Harvey viruses. BALB 3T3 cells transformed by RNA viruses (Kirsten, Harvey, or Moloney), by a DNA virus (SV40), by methylcholanthrene, or spontaneously, all have diminished but readily detectable guanylate cyclase activity. Cyclic GMP phosphodiesterase activity is found predominately in the soluble fraction of NRK cells. This activity increases slightly as NRK cells enter the stationary growth phase. Cyclic GMP phosphodiesterase activity is undetectable in two clones of KNRK cells under a variety of assay conditions, and is decreased relative to the level present in NRK cells in a third KNRK clone. However, both Moloney- and Schmidt-Ruppin-transformed NRK cells have a phosphodiesterase activity similar to that found in NRK cells. Boiled supernatant from both NRK and KNRK cells is observed to appreciably enhance the activity of activator-deficient phosphodiesterase from bovine heart. This result indicates that the absence of cyclic GMP phosphodiesterase activity in KNRK cells is not due to a loss of the phosphodiesterase activator. The intracellular concentration of cyclic GMP is found to be very low in transformed NRK cells when compared to levels measured in confluent NRK cells. The low levels of cyclic GMP in transformed NRK cells reflect the greatly decreased guanylate cyclase activity observed in these cells. These results do not appear to support the suggestion that cyclic GMP promotes the growth of fibroblastic cells.", "contents": "Guanylate cyclase and cyclic guanosine 3':5'-monophosphate phosphodiesterase activities and cyclic guanosine 3':5'-monophosphate levels in normal and transformed fibroblasts in culture. To investigate the role of guanosine 3':5'-monophosphate (cyclic GMP) in cultured cells we have measured guanylate cyclase and cyclic GMP phosphodiesterase activities and cyclic GMP levels in normal and transformed fibroblastic cells. Guanylate cyclase activity is found almost exclusively in the particulate fraction of normal rat kidney (NRK) and BALB 3T3 cells. Enzyme activity is stimulated 3- to 10-fold by treatment with the detergent Lubrol PX. However, enhancement of guanylate cyclase by fibroblast growth factor could not be demonstrated under a variety of assay conditions. In both NRK and BALB 3T3 cells guanylate cyclase activity is low during logarithmic growth and increases as the cells crowd together and growth slows. Guanylate cyclase activity is undetectable in homogenates of NRK cells transformed by the Kirsten sarcoma virus (KNRK cells) either in the presence or absence of Lubrol PX. Guanylate cyclase activity is also greatly decreased in NRK cells transformed by Moloney, Schmidt-Ruppin, or Harvey viruses. BALB 3T3 cells transformed by RNA viruses (Kirsten, Harvey, or Moloney), by a DNA virus (SV40), by methylcholanthrene, or spontaneously, all have diminished but readily detectable guanylate cyclase activity. Cyclic GMP phosphodiesterase activity is found predominately in the soluble fraction of NRK cells. This activity increases slightly as NRK cells enter the stationary growth phase. Cyclic GMP phosphodiesterase activity is undetectable in two clones of KNRK cells under a variety of assay conditions, and is decreased relative to the level present in NRK cells in a third KNRK clone. However, both Moloney- and Schmidt-Ruppin-transformed NRK cells have a phosphodiesterase activity similar to that found in NRK cells. Boiled supernatant from both NRK and KNRK cells is observed to appreciably enhance the activity of activator-deficient phosphodiesterase from bovine heart. This result indicates that the absence of cyclic GMP phosphodiesterase activity in KNRK cells is not due to a loss of the phosphodiesterase activator. The intracellular concentration of cyclic GMP is found to be very low in transformed NRK cells when compared to levels measured in confluent NRK cells. The low levels of cyclic GMP in transformed NRK cells reflect the greatly decreased guanylate cyclase activity observed in these cells. These results do not appear to support the suggestion that cyclic GMP promotes the growth of fibroblastic cells."}
{"id": "PMID:4445", "title": "Specificity of alpha-chymotrypsin with exposed carboxyl groups blocked.", "content": "The 15 exposed carboxyl groups of alpha-chymotrypsin were modified with glycine ethyl ester at low pH using barbodiimide reagent. The specificity of the modified enzyme (Chy-15) was studied over the pH range of 4 to 9 with both N-acylated and non-N-acylated amino acid esters. The modified enzyme had lower reactivity toward N-acylated esters than non-N-acylated esters compared to the native enzyme. Typical substances such as acetyl- and benzoyl-L-tyrosine ethyl esters retained 4 and 9% activity, whereas phenylalanine ethyl ester was slightly more reactive with the modified than with the native enzyme. The pH-rate profiles of acetyl-L-phenylalanine ethyl ester and tryptophan ethyl and benzyl esters were investigated in detail. Analysis of these profiles revealed three pKa values of approximately 5, 7, and 9 related to a functional carboxyl, imidazoyl, and an amino group, respectively. Since similar pKa values occur for the native enzyme, modification did not block the carboxyl corresponding to pKa 5. A mechanism is proposed for catalysis which includes both the protonated and unprotonated form of the imidazoyl (His-57) and utilizes water rather than a carboxyl (Asp-102) as the proton sink.", "contents": "Specificity of alpha-chymotrypsin with exposed carboxyl groups blocked. The 15 exposed carboxyl groups of alpha-chymotrypsin were modified with glycine ethyl ester at low pH using barbodiimide reagent. The specificity of the modified enzyme (Chy-15) was studied over the pH range of 4 to 9 with both N-acylated and non-N-acylated amino acid esters. The modified enzyme had lower reactivity toward N-acylated esters than non-N-acylated esters compared to the native enzyme. Typical substances such as acetyl- and benzoyl-L-tyrosine ethyl esters retained 4 and 9% activity, whereas phenylalanine ethyl ester was slightly more reactive with the modified than with the native enzyme. The pH-rate profiles of acetyl-L-phenylalanine ethyl ester and tryptophan ethyl and benzyl esters were investigated in detail. Analysis of these profiles revealed three pKa values of approximately 5, 7, and 9 related to a functional carboxyl, imidazoyl, and an amino group, respectively. Since similar pKa values occur for the native enzyme, modification did not block the carboxyl corresponding to pKa 5. A mechanism is proposed for catalysis which includes both the protonated and unprotonated form of the imidazoyl (His-57) and utilizes water rather than a carboxyl (Asp-102) as the proton sink."}
{"id": "PMID:4446", "title": "Evidence for the coordinate control of activity of liver glycogen synthase and phosphorylase by a single protein phosphatase.", "content": "Homogeneous rabbit liver phosphorylase phosphatase (Brandt, H., Capulong, Z. L., and Lee, E. Y. C. (1975) J. Biol. Chem. 250, 8038-8044) also dephosphorylates glycogen synthase b. During purification, phosphorylase phosphatase and glycogen synthase phosphatase co-purified with a constant ratio of activities. The two activities co-migrated on disc gel electrophoresis. Both substrates competed with each other for the phosphatase, and both phosphatase activities were inhibited by lysine ethyl ester. It is concluded that liver phosphorylase phosphatase and glycogen synthase phosphatase have a common identity and that coordinate regulation of the phosphatase-catalyzed activation of glycogen synthase and inactivation of phosphorylase occurs in vivo. This provides a parallel and opposing mechanism to that mediated by adenosine 3':5'-monophosphate-dependent protein kinase, which coordinately inactivates glycogen synthase and, via phosphorylase kinase, activates phosphorylase. Maximal glycogen synthase phosphatase activity was observed near neutrality. Mg2+ and glucose-6-P activated the glycogen synthase phosphatase reaction and this activation was pH-dependent. The Km for glycogen synthase b was 0.12 muM.", "contents": "Evidence for the coordinate control of activity of liver glycogen synthase and phosphorylase by a single protein phosphatase. Homogeneous rabbit liver phosphorylase phosphatase (Brandt, H., Capulong, Z. L., and Lee, E. Y. C. (1975) J. Biol. Chem. 250, 8038-8044) also dephosphorylates glycogen synthase b. During purification, phosphorylase phosphatase and glycogen synthase phosphatase co-purified with a constant ratio of activities. The two activities co-migrated on disc gel electrophoresis. Both substrates competed with each other for the phosphatase, and both phosphatase activities were inhibited by lysine ethyl ester. It is concluded that liver phosphorylase phosphatase and glycogen synthase phosphatase have a common identity and that coordinate regulation of the phosphatase-catalyzed activation of glycogen synthase and inactivation of phosphorylase occurs in vivo. This provides a parallel and opposing mechanism to that mediated by adenosine 3':5'-monophosphate-dependent protein kinase, which coordinately inactivates glycogen synthase and, via phosphorylase kinase, activates phosphorylase. Maximal glycogen synthase phosphatase activity was observed near neutrality. Mg2+ and glucose-6-P activated the glycogen synthase phosphatase reaction and this activation was pH-dependent. The Km for glycogen synthase b was 0.12 muM."}
{"id": "PMID:4447", "title": "Solubilization and characterization of the beta-adrenergic receptor binding sites of frog erythrocytes.", "content": "Specific beta-adrenergic receptors present in membrane preparations of frog erythrocytes were identified by binding of (-)-[3H]dihydroalprenolol, a potent competitive beta-adrenergic antagonist. The (-)-[3H]dihydroalprenolol binding sites could be solubilized by treatment of a purified erythrocyte membrane fraction with the plant glycoside digitonin but not by treatment with a wide variety of other detergents. The binding sites appeared to be soluble by several independent experimental criteria including (a) failure to sediment of 105,000 X g for 2 hours; (b) passage through 0.22-mu Millipore filters; (c) chromatography on Sepharose 6B gels; and (d) electron microscopy. The soluble receptor sites retained all of the essential characteristics of the membrane-bound sites, namely rapid and reversible binding of beta-adrenergic agonists and antagonists; strict stereospecificity toward both beta-adrenergic agonists and antagonists; appropriate structure-activity relationships; saturability of the sites at low concentrations of ligand; no affinity for alpha-adrenergic drugs, nonphysiologically active catechol compounds, and catecholamine metabolites. Based on gel chromatography in the presence of detergent, the molecular weight of the soluble receptor is estimated to be no greater than 130,000 to 150,000. Equilibrium binding studies indicated a KD for the soluble receptor of 2 nM. Hill coefficients (nH) of 0.77 and curved Scatchard plots suggested the presence of negatively cooperative interactions among the solubilized receptors in agreement with previous findings with the membrane-bound sites. Kinetic studies indicated an association rate constant K1 = 3.8 X 10(6) M-1 min-1 and a reverse rate constant k2 = 2.3 X 10(-3) min-1 at 4 degrees. The kinetically derived KD (k2/k1) of 0.6 nM is in reasonable agreement with that determined by equilibrium studies. The soluble receptors were labile at temperature greater than 4 degrees but could be stabilized with high concentrations of EDTA. Guanidine hydrochloride and urea produced concentration-dependent losses of binding activity which were partially reversible upon dialysis. Trypsin and phospholipase A both degraded the soluble receptors but a variety of other proteases and phospholipases as well as DNase and RNase were without effect. Experiments with group-specific reagents indicated that free lysine, tryptophan, serine, and sulfhydryl groups may be important for receptor binding. These studies suggest that the receptor is probably a protein which requires lipids for functional integrity. Data obtained with the solubilized binding sites are consistent with the contention that these sites represent the physiologically relevant beta-adrenergic receptors which have been extracted from the membranes with full retention of their properties.", "contents": "Solubilization and characterization of the beta-adrenergic receptor binding sites of frog erythrocytes. Specific beta-adrenergic receptors present in membrane preparations of frog erythrocytes were identified by binding of (-)-[3H]dihydroalprenolol, a potent competitive beta-adrenergic antagonist. The (-)-[3H]dihydroalprenolol binding sites could be solubilized by treatment of a purified erythrocyte membrane fraction with the plant glycoside digitonin but not by treatment with a wide variety of other detergents. The binding sites appeared to be soluble by several independent experimental criteria including (a) failure to sediment of 105,000 X g for 2 hours; (b) passage through 0.22-mu Millipore filters; (c) chromatography on Sepharose 6B gels; and (d) electron microscopy. The soluble receptor sites retained all of the essential characteristics of the membrane-bound sites, namely rapid and reversible binding of beta-adrenergic agonists and antagonists; strict stereospecificity toward both beta-adrenergic agonists and antagonists; appropriate structure-activity relationships; saturability of the sites at low concentrations of ligand; no affinity for alpha-adrenergic drugs, nonphysiologically active catechol compounds, and catecholamine metabolites. Based on gel chromatography in the presence of detergent, the molecular weight of the soluble receptor is estimated to be no greater than 130,000 to 150,000. Equilibrium binding studies indicated a KD for the soluble receptor of 2 nM. Hill coefficients (nH) of 0.77 and curved Scatchard plots suggested the presence of negatively cooperative interactions among the solubilized receptors in agreement with previous findings with the membrane-bound sites. Kinetic studies indicated an association rate constant K1 = 3.8 X 10(6) M-1 min-1 and a reverse rate constant k2 = 2.3 X 10(-3) min-1 at 4 degrees. The kinetically derived KD (k2/k1) of 0.6 nM is in reasonable agreement with that determined by equilibrium studies. The soluble receptors were labile at temperature greater than 4 degrees but could be stabilized with high concentrations of EDTA. Guanidine hydrochloride and urea produced concentration-dependent losses of binding activity which were partially reversible upon dialysis. Trypsin and phospholipase A both degraded the soluble receptors but a variety of other proteases and phospholipases as well as DNase and RNase were without effect. Experiments with group-specific reagents indicated that free lysine, tryptophan, serine, and sulfhydryl groups may be important for receptor binding. These studies suggest that the receptor is probably a protein which requires lipids for functional integrity. Data obtained with the solubilized binding sites are consistent with the contention that these sites represent the physiologically relevant beta-adrenergic receptors which have been extracted from the membranes with full retention of their properties."}
{"id": "PMID:4448", "title": "Reconstitution and characterization of the adenine nucleotide transporter derived from bovine heart mitochondria.", "content": "1. Adenine nucleotide exchange-transport was reconstituted in vesicles prepared from phospholipids and protein fractions derived from bovine heart submitochondrial particles. The transport, which was specific for ATP and ADP was measured either as ADP/ADP, ATP/ATP, or ADP/ATP exchange. The highest specific activity (370 nanomoles of ADP/ADP exchange/min/mg of protein at room temperature) was obtained with a protein fraction prepared by cholate extraction of partly resolved submitochondrial particles followed by ammonium sulfate fractionation. 2. At 200 muM external nucleotide, the exchange reactions were inhibited by low concentrations of bongkrekate, atractyloside, and palmitoyl-CoA, with Ki values of 1.8, 3.0, and 7.5 muM, respectively. The ADP/ADP nucleotide exchange was stimulated about 5-fold by 500 muM MgCl2 or MnCl2(km of 40 muM) and about 3-fold by 500 muM CaCl2(Km of 90 muM). It was optimal between pH 6.0 and 7.0 and decreased rapidly above pH 7.5. Arrhenius plots between 0 degrees and 40 degrees showed a break point at 15 degrees with soybean phospholipids and an activation energy of 29.5 kcal/mole from 0 degrees-15 degrees and 9.0 kcal/mole from 15 degrees-40 degrees. With mitochondrial phospholipids the break point was at 9 degrees and activation energies were 42.4 kcal/mole from 0 degrees-9 degrees and 7.6 kcal/mole from 9 degrees-40 degrees. 3. The phospholipid requirements for adenine nucleotide exchange were similar to those of oxidative phosphorylation. Optimal rates were observed with a phosphatidylethanolamine to phosphatidylcholine ratio of 4:1. Cardiolipin had a slight stimulatory effect. 4. The uptake of ADP into vesicles containing ATP was stimulated by KCl or by KPi as well as by hexafluoracetonylacetone, and uncoupler of oxidative phosphorylation. The uptake of ATP into vesicles containing ADP was inhibited by KCl or by KPi, but was also stimulated by hexafluoracetonylacetone. In both cases valinomycin reversed the effects of KCl, while mersalyl or N-ethylmaleimide prevented the effects of KPi. In contrast, none of these salts nor hexafluoracetonylactone affected the ADP/ADP or ATP/ATP exchange. These findings suggest that in the reconstituted system the ADP/ATP exchange is electrogenic.", "contents": "Reconstitution and characterization of the adenine nucleotide transporter derived from bovine heart mitochondria. 1. Adenine nucleotide exchange-transport was reconstituted in vesicles prepared from phospholipids and protein fractions derived from bovine heart submitochondrial particles. The transport, which was specific for ATP and ADP was measured either as ADP/ADP, ATP/ATP, or ADP/ATP exchange. The highest specific activity (370 nanomoles of ADP/ADP exchange/min/mg of protein at room temperature) was obtained with a protein fraction prepared by cholate extraction of partly resolved submitochondrial particles followed by ammonium sulfate fractionation. 2. At 200 muM external nucleotide, the exchange reactions were inhibited by low concentrations of bongkrekate, atractyloside, and palmitoyl-CoA, with Ki values of 1.8, 3.0, and 7.5 muM, respectively. The ADP/ADP nucleotide exchange was stimulated about 5-fold by 500 muM MgCl2 or MnCl2(km of 40 muM) and about 3-fold by 500 muM CaCl2(Km of 90 muM). It was optimal between pH 6.0 and 7.0 and decreased rapidly above pH 7.5. Arrhenius plots between 0 degrees and 40 degrees showed a break point at 15 degrees with soybean phospholipids and an activation energy of 29.5 kcal/mole from 0 degrees-15 degrees and 9.0 kcal/mole from 15 degrees-40 degrees. With mitochondrial phospholipids the break point was at 9 degrees and activation energies were 42.4 kcal/mole from 0 degrees-9 degrees and 7.6 kcal/mole from 9 degrees-40 degrees. 3. The phospholipid requirements for adenine nucleotide exchange were similar to those of oxidative phosphorylation. Optimal rates were observed with a phosphatidylethanolamine to phosphatidylcholine ratio of 4:1. Cardiolipin had a slight stimulatory effect. 4. The uptake of ADP into vesicles containing ATP was stimulated by KCl or by KPi as well as by hexafluoracetonylacetone, and uncoupler of oxidative phosphorylation. The uptake of ATP into vesicles containing ADP was inhibited by KCl or by KPi, but was also stimulated by hexafluoracetonylacetone. In both cases valinomycin reversed the effects of KCl, while mersalyl or N-ethylmaleimide prevented the effects of KPi. In contrast, none of these salts nor hexafluoracetonylactone affected the ADP/ADP or ATP/ATP exchange. These findings suggest that in the reconstituted system the ADP/ATP exchange is electrogenic."}
{"id": "PMID:4449", "title": "Solubilization of thyroid peroxidase by nonionic detergents.", "content": "We have examined the ability of nonionic detergents to solubilize thyroid peroxidase from a porcine thyroid particulate fraction, as measured by the release of peroxidase activity into the supernatant fraction after centrifugation at 105,000 X g for 1 hour and the retardation of the supernatant peroxidase of Sepharose 6B. The parameters of peroxidase solubilization by Triton X-100 have been investigated in detail. Under optimum conditions, 60 to 95% of the thryoid peroxidase and about 50% of the total protein is released into the 105,000 X g, 1-hour supernatant. Under the optimum conditions established with Triton X-100, a series of Brij detergents of different chemical structure were equally effective in releasing peroxidase and protein. The protein patterns of the supernatants obtained with these detergents were similar on sodium dodecyl sulfate-polyacrylamide electrophoresis gels, suggesting that the detergents studied release similar membrane proteins. The Triton X-100 and Brij 58 supernatants were chromatographed separately on Sepharose 6B equilibrated with 0.1% Triton X-100 or Brij 58, respectively. In both cases, 75 to 80% of the peroxidase activity was retarded, thereby indicating that the nonionic detergents effect solubilization of the peroxidase rather than dispersal of nonsedimentable membrane fragments. These studies report the first successful solubilization of thyroid peroxidase by nonionic detergents. Together with previous evidence from our laboratory, these experiments indicate that thyroid peroxidase is an integral membrane protein.", "contents": "Solubilization of thyroid peroxidase by nonionic detergents. We have examined the ability of nonionic detergents to solubilize thyroid peroxidase from a porcine thyroid particulate fraction, as measured by the release of peroxidase activity into the supernatant fraction after centrifugation at 105,000 X g for 1 hour and the retardation of the supernatant peroxidase of Sepharose 6B. The parameters of peroxidase solubilization by Triton X-100 have been investigated in detail. Under optimum conditions, 60 to 95% of the thryoid peroxidase and about 50% of the total protein is released into the 105,000 X g, 1-hour supernatant. Under the optimum conditions established with Triton X-100, a series of Brij detergents of different chemical structure were equally effective in releasing peroxidase and protein. The protein patterns of the supernatants obtained with these detergents were similar on sodium dodecyl sulfate-polyacrylamide electrophoresis gels, suggesting that the detergents studied release similar membrane proteins. The Triton X-100 and Brij 58 supernatants were chromatographed separately on Sepharose 6B equilibrated with 0.1% Triton X-100 or Brij 58, respectively. In both cases, 75 to 80% of the peroxidase activity was retarded, thereby indicating that the nonionic detergents effect solubilization of the peroxidase rather than dispersal of nonsedimentable membrane fragments. These studies report the first successful solubilization of thyroid peroxidase by nonionic detergents. Together with previous evidence from our laboratory, these experiments indicate that thyroid peroxidase is an integral membrane protein."}
{"id": "PMID:4450", "title": "Carbon 13 magnetic resonance studies of DL-2-(alpha-hydroxyethyl) thiamin and related compounds. Relation of kinetic acidity to electronic factors in thiamin catalysis.", "content": "Carbon 13 NMR spectra have been obtained for aqueous solutions of DL-2-(alpha-hydroxyethyl)thiamin, DL-2-(alpha-hydroxybenzyl)thiamin, DL-2-(alpha-hydroxybenzyl)oxythiamin, and related N-3 methyl and N-3 benzyl analogs. The unusually large downfield shift of the 13C resonance of C-2 of hydroxyethylthiamin suggests that this carbon bears a partial positive charge. This result stands in contrast to results of x-ray crystallographic studies of hydroxyethylthiamin, which place a partial negative charge on C-2 (Pletcher, J., and Sax, M. (1974) J. Am. Chem. Soc. 96, 155-165). A partial positive charge on C-2 helps to explain the facility of carbanion formation at the alpha carbon both enzymatically and in model systems. The rates of proton-deuteron exchange of (C-alpha)-H with solvent deuterium, and of release of aldehyde to regenerate thiamin have been measured for hydroxyethylthiamin and analogs. The differences in kinetic acidity of (C-alpha)-H and of rates of aldehyde release are rationalized in terms of differing electron-withdrawing abilities of the substituents attached to N-3, and appear not to be related to intramolecular basic catalysis of these processes by the C-4' amino group.", "contents": "Carbon 13 magnetic resonance studies of DL-2-(alpha-hydroxyethyl) thiamin and related compounds. Relation of kinetic acidity to electronic factors in thiamin catalysis. Carbon 13 NMR spectra have been obtained for aqueous solutions of DL-2-(alpha-hydroxyethyl)thiamin, DL-2-(alpha-hydroxybenzyl)thiamin, DL-2-(alpha-hydroxybenzyl)oxythiamin, and related N-3 methyl and N-3 benzyl analogs. The unusually large downfield shift of the 13C resonance of C-2 of hydroxyethylthiamin suggests that this carbon bears a partial positive charge. This result stands in contrast to results of x-ray crystallographic studies of hydroxyethylthiamin, which place a partial negative charge on C-2 (Pletcher, J., and Sax, M. (1974) J. Am. Chem. Soc. 96, 155-165). A partial positive charge on C-2 helps to explain the facility of carbanion formation at the alpha carbon both enzymatically and in model systems. The rates of proton-deuteron exchange of (C-alpha)-H with solvent deuterium, and of release of aldehyde to regenerate thiamin have been measured for hydroxyethylthiamin and analogs. The differences in kinetic acidity of (C-alpha)-H and of rates of aldehyde release are rationalized in terms of differing electron-withdrawing abilities of the substituents attached to N-3, and appear not to be related to intramolecular basic catalysis of these processes by the C-4' amino group."}
{"id": "PMID:4451", "title": "Oxygen and carbon monoxide kinetics of Glycera dibranchiata monomeric hemoglobin.", "content": "Oxygen and carbon monoxide kinetics of Glycera dibranchiata monomeric hemoglobin have been studied using laser photolysis, air flash, and stopped flow techniques. The reactions of this hemoglobin with both ligands were found to be more rapid than the corresponding reactions involving myoglobin and were also biphasic in nature, the rate constants being approximately an order of magnitude different for the fast and slow phases in each case. No pH or hemoglobin concentration dependence of the pseudo-first order rate constants was apparent between pH 6 and 9 and in the concentration range of 1.25 to 40 muM heme. Both fast and slow pseudo-first order oxygen combination rate constants varied linearly with oxygen concentration between 16 and 1300 muM. A first order slow relaxation was also noted which was linearly dependent on heme concentration and inversely dependent on oxygen concentration. This reaction has been shown to be due to a replacement of oxygen by carbon monoxide. The presence of this reaction is a result of the high affinity of Glycera monomer for carbon monoxide as shown by the partition coefficient Mr = approximately 20,000 ana an equilibrium dissociation constant of the order L = 1.1 X 10(-9) M.", "contents": "Oxygen and carbon monoxide kinetics of Glycera dibranchiata monomeric hemoglobin. Oxygen and carbon monoxide kinetics of Glycera dibranchiata monomeric hemoglobin have been studied using laser photolysis, air flash, and stopped flow techniques. The reactions of this hemoglobin with both ligands were found to be more rapid than the corresponding reactions involving myoglobin and were also biphasic in nature, the rate constants being approximately an order of magnitude different for the fast and slow phases in each case. No pH or hemoglobin concentration dependence of the pseudo-first order rate constants was apparent between pH 6 and 9 and in the concentration range of 1.25 to 40 muM heme. Both fast and slow pseudo-first order oxygen combination rate constants varied linearly with oxygen concentration between 16 and 1300 muM. A first order slow relaxation was also noted which was linearly dependent on heme concentration and inversely dependent on oxygen concentration. This reaction has been shown to be due to a replacement of oxygen by carbon monoxide. The presence of this reaction is a result of the high affinity of Glycera monomer for carbon monoxide as shown by the partition coefficient Mr = approximately 20,000 ana an equilibrium dissociation constant of the order L = 1.1 X 10(-9) M."}
{"id": "PMID:4452", "title": "Analysis of phosphate metabolites, the intracellular pH, and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic resonance.", "content": "31P nuclear magnetic resonance spectra recorded from intact muophosphate, and the sugar phosphates. Quantitation of these metabolites by 31P nuclear magnetic resonance was in good agreement with values obtained by chemical analyses. The spectra obtained from various muscles showed considerable variation in their phosphorus profile. Thus, differences could be detected between (a) normal and diseased muscle; (b) vertebrates and invertebrates; (c) different species of the same animal. The time course of change in phosphate metabolites in frog muscle showed that ATP level remains unchanged until phosphocreatine is nearly depleted. Comparative studies revealed that under anaerobic conditions the Northern frog maintains its ATP content for 7 hours, while other types of amphibian, bird, and mammalian muscles begin to show an appreciable decay in ATP after 2 hours. Several lines of evidence indicated that ATP forms a complex with magnesium in the muscle water: (a) the phosphate resonances of ATP in the muscle were shifted downfield as compared to those in the alkaline earth metal-free perchloric acid extract of the muscle; (b) the coupling constants of ATP measured in various live muscles closely corresponded to those for MgATP in a solution resembling the composition of the muscle water; (c) in the muscle the gamma-phosphate group of ATP exhibited no shift change over a period of 10 hours under conditions where resonances of other phosphate compounds could be titrated. This behavior is similar to that of MgATP in model solutions in the physiological pH range, and it is different from that of CaATP. The chemical shifts of the phosphate metabolites were determined in several relevant solutions as a function of pH. Under all conditions only inorganic orthophosphate showed an invariant titration curve. From the chemical shift of inorganic phosphate observed during aging of intact muscle the intracellular pH of frog muscle was estimated to be 7.2.", "contents": "Analysis of phosphate metabolites, the intracellular pH, and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic resonance. 31P nuclear magnetic resonance spectra recorded from intact muophosphate, and the sugar phosphates. Quantitation of these metabolites by 31P nuclear magnetic resonance was in good agreement with values obtained by chemical analyses. The spectra obtained from various muscles showed considerable variation in their phosphorus profile. Thus, differences could be detected between (a) normal and diseased muscle; (b) vertebrates and invertebrates; (c) different species of the same animal. The time course of change in phosphate metabolites in frog muscle showed that ATP level remains unchanged until phosphocreatine is nearly depleted. Comparative studies revealed that under anaerobic conditions the Northern frog maintains its ATP content for 7 hours, while other types of amphibian, bird, and mammalian muscles begin to show an appreciable decay in ATP after 2 hours. Several lines of evidence indicated that ATP forms a complex with magnesium in the muscle water: (a) the phosphate resonances of ATP in the muscle were shifted downfield as compared to those in the alkaline earth metal-free perchloric acid extract of the muscle; (b) the coupling constants of ATP measured in various live muscles closely corresponded to those for MgATP in a solution resembling the composition of the muscle water; (c) in the muscle the gamma-phosphate group of ATP exhibited no shift change over a period of 10 hours under conditions where resonances of other phosphate compounds could be titrated. This behavior is similar to that of MgATP in model solutions in the physiological pH range, and it is different from that of CaATP. The chemical shifts of the phosphate metabolites were determined in several relevant solutions as a function of pH. Under all conditions only inorganic orthophosphate showed an invariant titration curve. From the chemical shift of inorganic phosphate observed during aging of intact muscle the intracellular pH of frog muscle was estimated to be 7.2."}
{"id": "PMID:4453", "title": "5' leads to 3'-Exonucleases of bacteriophage T4.", "content": "Two enzyme activities which release nucleotides preferentially from the 5' termini of DNA were found in T4-infected Escherichia coli. Since no corresponding activities were found in uninfected cells, the activities appeared to be induced by T4. Both activities are capable of excising pyrimidine dimers from ultraviolet-irradiated DNA which has been treated with T4 endonuclease V. One of the activities , referred to as T4 exonuclease B, was purified 400-fold from an extract of T4v 1- infected cells. The enzyme initiates hydrolysis of DNA specifically at the 5' termini to yield products which are mainly oligonucleotides of varying length. The hydrolysis reaction proceeds in a limited manner. The enzyme shows optimal activity at pH 7.0 and absolutely requires Mg2+. The molecular weight of the enzyme , as estimated by gel filtration, is approximately 35,000. Another activity, referred to as T4 exonuclease C, was purified 240-fold from the extract. This activity also excises pyrimidine dimers from ultraviolet-irradiated, incised DNA and releases nucleotides at 5' termini. It has a pH optimum at 7.5 and requires Mg2+. The molecular weight of the enzyme is approximately 20,000.", "contents": "5' leads to 3'-Exonucleases of bacteriophage T4. Two enzyme activities which release nucleotides preferentially from the 5' termini of DNA were found in T4-infected Escherichia coli. Since no corresponding activities were found in uninfected cells, the activities appeared to be induced by T4. Both activities are capable of excising pyrimidine dimers from ultraviolet-irradiated DNA which has been treated with T4 endonuclease V. One of the activities , referred to as T4 exonuclease B, was purified 400-fold from an extract of T4v 1- infected cells. The enzyme initiates hydrolysis of DNA specifically at the 5' termini to yield products which are mainly oligonucleotides of varying length. The hydrolysis reaction proceeds in a limited manner. The enzyme shows optimal activity at pH 7.0 and absolutely requires Mg2+. The molecular weight of the enzyme , as estimated by gel filtration, is approximately 35,000. Another activity, referred to as T4 exonuclease C, was purified 240-fold from the extract. This activity also excises pyrimidine dimers from ultraviolet-irradiated, incised DNA and releases nucleotides at 5' termini. It has a pH optimum at 7.5 and requires Mg2+. The molecular weight of the enzyme is approximately 20,000."}
{"id": "PMID:4454", "title": "Nuclear magnetic resonance titration curves of histidine ring protons. A direct assignment of the resonances of the active site histidine residues of ribonuclease.", "content": "One of the four titrating histidine ring C-2 proton resonances of bovine pancreatic ribonuclease has been assigned to histidine residue 12. This was accomplished by a direct comparison of the rate of tritium incorporation into position C-2 of histidine 12 of S-peptide (residues 1 to 20) derived from ribonuclease S, with the rates of deuterium exchange of the four histidine C-2 proton resonances of ribonuclease S under the same experimental conditions. The same assignment was obtained by a comparison of the NMR titration curves of ribonuclease S, the noncovalent complex of S-peptide and S-protein (residues 21 to 124) with the results for the recombined complex in which position C-2 of histidine 12 was fully deuterated. The second active site histidine resonance was assigned to histidine residue 119 by consideration of the NMR titration results fro carboxymethylated histidines and 1-carboxymethylhistidine 119 ribonuclease. This assignment is a reversal of that originally reported, and has important implications for the interpretation of NMR titration data of ribonuclease.", "contents": "Nuclear magnetic resonance titration curves of histidine ring protons. A direct assignment of the resonances of the active site histidine residues of ribonuclease. One of the four titrating histidine ring C-2 proton resonances of bovine pancreatic ribonuclease has been assigned to histidine residue 12. This was accomplished by a direct comparison of the rate of tritium incorporation into position C-2 of histidine 12 of S-peptide (residues 1 to 20) derived from ribonuclease S, with the rates of deuterium exchange of the four histidine C-2 proton resonances of ribonuclease S under the same experimental conditions. The same assignment was obtained by a comparison of the NMR titration curves of ribonuclease S, the noncovalent complex of S-peptide and S-protein (residues 21 to 124) with the results for the recombined complex in which position C-2 of histidine 12 was fully deuterated. The second active site histidine resonance was assigned to histidine residue 119 by consideration of the NMR titration results fro carboxymethylated histidines and 1-carboxymethylhistidine 119 ribonuclease. This assignment is a reversal of that originally reported, and has important implications for the interpretation of NMR titration data of ribonuclease."}
{"id": "PMID:4455", "title": "Nuclear magnetic resonance titration curves of histidine ring protons. Ribonuclease S-peptide and S-proteins.", "content": "The histidine C-2 proton NMR titration curves of ribonuclease S-peptide (residues 1 to 20) and S-protein (residues 21 to 124) are reported. Although S-protein contains 3 histidine residues, four discrete resonances are observed to titrate. One of these arises from the equivalent histidine residues of unfolded S-protein. The variation in area of the four resonances indicate that there is a reversible pH-dependent equilibrium between the folded and unfolded forms of S-protein, with some unfolded material being present at most pH values. Two of the resonances of the folded S-protein can be assigned to 2 of the histidine residues, 48 and 105, from the close similarity of their titration curves to those in ribonuclease. These similarities indicate a homology of portions of the folded conformation of S-protein to that of ribonuclease in solution. These results indicate that the complete amino acid sequence is not required to produce a folded conformation similar to the native globular protein, and they appear to eliminate the possibility that proteins fold from their NH2 terminus during protein synthesis. The low pH inflection present in the titration curve assigned to histidine residue 48 in ribonuclease is absent from this curve in S-protein. This is consistent with our previous conclusion that this inflection arises from the interaction of histidine 48 with aspartic acid residue 14, which is also absent in S-protein. The third titrating resonance of native S-protein is assigned to the remaining histidine residue at position 119. The properties of this resonance are not identical with either of the titration curves of the active site histidine residues 12 and 119 of ribonuclease. The resonance assigned to histidine 119 is the only one significantly affected on the addition of sodium phosphate to S-protein, indicating that some degree of phosphate binding occurs. In both the absence and presence of phosphate this curve also lacks the low pH inflection observed in the histidine 119 NMR titration curve in ribonuclease. This difference presumably arise from a conformational between ribonuclease and the folded S-protein involving a carboxyl group.", "contents": "Nuclear magnetic resonance titration curves of histidine ring protons. Ribonuclease S-peptide and S-proteins. The histidine C-2 proton NMR titration curves of ribonuclease S-peptide (residues 1 to 20) and S-protein (residues 21 to 124) are reported. Although S-protein contains 3 histidine residues, four discrete resonances are observed to titrate. One of these arises from the equivalent histidine residues of unfolded S-protein. The variation in area of the four resonances indicate that there is a reversible pH-dependent equilibrium between the folded and unfolded forms of S-protein, with some unfolded material being present at most pH values. Two of the resonances of the folded S-protein can be assigned to 2 of the histidine residues, 48 and 105, from the close similarity of their titration curves to those in ribonuclease. These similarities indicate a homology of portions of the folded conformation of S-protein to that of ribonuclease in solution. These results indicate that the complete amino acid sequence is not required to produce a folded conformation similar to the native globular protein, and they appear to eliminate the possibility that proteins fold from their NH2 terminus during protein synthesis. The low pH inflection present in the titration curve assigned to histidine residue 48 in ribonuclease is absent from this curve in S-protein. This is consistent with our previous conclusion that this inflection arises from the interaction of histidine 48 with aspartic acid residue 14, which is also absent in S-protein. The third titrating resonance of native S-protein is assigned to the remaining histidine residue at position 119. The properties of this resonance are not identical with either of the titration curves of the active site histidine residues 12 and 119 of ribonuclease. The resonance assigned to histidine 119 is the only one significantly affected on the addition of sodium phosphate to S-protein, indicating that some degree of phosphate binding occurs. In both the absence and presence of phosphate this curve also lacks the low pH inflection observed in the histidine 119 NMR titration curve in ribonuclease. This difference presumably arise from a conformational between ribonuclease and the folded S-protein involving a carboxyl group."}
{"id": "PMID:4456", "title": "Effects of formylation of vinyl side chains of heme on optical and ligand binding properties of horse heart ferric myoglobin.", "content": "Effects of substitution of vinyl groups of hemin with formyl groups on the optical and ligand binding properties of horse heart ferric myoglobin were investigated. The peak positions as well as the line shapes of the absorption spectra of the ferric derivatives of three kinds of formylmyoglobin, 2-vinyl-4-formyl-, 2-formyl-4-vinyl-, and 2,4-diformylmyoglobins depend on the number and the position of the formyl groups. Absorption maxima in the Soret region of the acid forms of these ferric formylmyoglobins in 0.1 M potassium phosphate buffer, pH 6.0, at 20 degrees were 415.2, 422, and 429 nm, respectively. The acid forms of these formylmyoglobins exhibit absorption spectra of the mixture of high- and low spin states at ambient temperature. Since proto-, deutero- and mesomyoglobins have a high spin state under the same condition, the increase of the low spin iron in these formylmyoglobins may be due to the strong electron withdrawal by the formyl groups toward the periphery of the porphyrin ring. The affinities of these ferric formylmyoglobins and protomyoglobin for N3-, F-, OCN-, and SCN- increased in the order of proto-, monoformyl-monovinyl-, 2,4-diformyl-myoglobin, which corresponds to the increasing order of electron-withdrawing power of the porphyrin side chains. The pKa values of the acid-alkaline transition decreased in the same order. Although the ferric forms of the two isomeric monoformyl-monovinylmyoglobins exhibited different optical spectra, the dissociation constants of the complexes of these isomers for various ligands were similar to each other. The pKa values of the acid-alkaline transition were also similar. These results indicate that affinities of ferric myoglobin for ligands, in contrast to those of the ferrous form for oxygen and carbon monoxide (Sono, M., and Asakura, T. (1975) J. Biol. Chem. 250, 5527-5232 and Sono, M., Smith, P.D., McCray, J.A., and Asakura, T. (1976) J. Biol. Chem 251, 1418-1426), are not affected by the position of modifications at the two vinyl groups, but are determinedby the number of the formyl groups and that two vinyl groups at position 2 and 4 are equivalent in the binding of various ligands by ferric myoglobin. The electron density of the ferric iron appears to be similar for the two isomeric monoformyl-monovinylmyoglobins.", "contents": "Effects of formylation of vinyl side chains of heme on optical and ligand binding properties of horse heart ferric myoglobin. Effects of substitution of vinyl groups of hemin with formyl groups on the optical and ligand binding properties of horse heart ferric myoglobin were investigated. The peak positions as well as the line shapes of the absorption spectra of the ferric derivatives of three kinds of formylmyoglobin, 2-vinyl-4-formyl-, 2-formyl-4-vinyl-, and 2,4-diformylmyoglobins depend on the number and the position of the formyl groups. Absorption maxima in the Soret region of the acid forms of these ferric formylmyoglobins in 0.1 M potassium phosphate buffer, pH 6.0, at 20 degrees were 415.2, 422, and 429 nm, respectively. The acid forms of these formylmyoglobins exhibit absorption spectra of the mixture of high- and low spin states at ambient temperature. Since proto-, deutero- and mesomyoglobins have a high spin state under the same condition, the increase of the low spin iron in these formylmyoglobins may be due to the strong electron withdrawal by the formyl groups toward the periphery of the porphyrin ring. The affinities of these ferric formylmyoglobins and protomyoglobin for N3-, F-, OCN-, and SCN- increased in the order of proto-, monoformyl-monovinyl-, 2,4-diformyl-myoglobin, which corresponds to the increasing order of electron-withdrawing power of the porphyrin side chains. The pKa values of the acid-alkaline transition decreased in the same order. Although the ferric forms of the two isomeric monoformyl-monovinylmyoglobins exhibited different optical spectra, the dissociation constants of the complexes of these isomers for various ligands were similar to each other. The pKa values of the acid-alkaline transition were also similar. These results indicate that affinities of ferric myoglobin for ligands, in contrast to those of the ferrous form for oxygen and carbon monoxide (Sono, M., and Asakura, T. (1975) J. Biol. Chem. 250, 5527-5232 and Sono, M., Smith, P.D., McCray, J.A., and Asakura, T. (1976) J. Biol. Chem 251, 1418-1426), are not affected by the position of modifications at the two vinyl groups, but are determinedby the number of the formyl groups and that two vinyl groups at position 2 and 4 are equivalent in the binding of various ligands by ferric myoglobin. The electron density of the ferric iron appears to be similar for the two isomeric monoformyl-monovinylmyoglobins."}
{"id": "PMID:4457", "title": "An essential residue at the active site of aspartate transcarbamylase.", "content": "Reaction of phenylglyoxal with aspartate transcarbamylase and its isolated catalytic subunit results in complete loss of enzymatic activity. This modification reaction is markedly influenced by pH and is partially reversible upon dialysis. Carbamyl phosphate or carbamyl phosphate with succinate partially protect the catalytic subunit and the native enzyme from inactivation by phenylglyoxal. In the native enzyme complete protection from inactivation is afforded by N-(phosphonacetyl)-L-aspartate. The decrease in enzymatic activity correlates with the modification of 6 arginine residues on each aspartate transcarbamylase molecule, i.e. 1 arginine per catalytic site. The data suggest that the essential arginine is involved in the binding of carbamyl phosphate to the enzyme. Reaction of the single thiol on the catalytic chain with 2-chloromercuri-4-nitrophenol does not prevent subsequent reaction with phenylglyoxal. If N-(phosphonacetyl)-L-aspartate is used to protect the active site we find that phenylglyoxal also causes the loss of activation of ATP and inhibition by CTP. The rate of loss of heterotropic effects is exactly the same for both nucleotides indicating that the two opposite regulatory effects originate at the same location on the enzyme, or are transmitted by the same mechanism between the subunits, or both.", "contents": "An essential residue at the active site of aspartate transcarbamylase. Reaction of phenylglyoxal with aspartate transcarbamylase and its isolated catalytic subunit results in complete loss of enzymatic activity. This modification reaction is markedly influenced by pH and is partially reversible upon dialysis. Carbamyl phosphate or carbamyl phosphate with succinate partially protect the catalytic subunit and the native enzyme from inactivation by phenylglyoxal. In the native enzyme complete protection from inactivation is afforded by N-(phosphonacetyl)-L-aspartate. The decrease in enzymatic activity correlates with the modification of 6 arginine residues on each aspartate transcarbamylase molecule, i.e. 1 arginine per catalytic site. The data suggest that the essential arginine is involved in the binding of carbamyl phosphate to the enzyme. Reaction of the single thiol on the catalytic chain with 2-chloromercuri-4-nitrophenol does not prevent subsequent reaction with phenylglyoxal. If N-(phosphonacetyl)-L-aspartate is used to protect the active site we find that phenylglyoxal also causes the loss of activation of ATP and inhibition by CTP. The rate of loss of heterotropic effects is exactly the same for both nucleotides indicating that the two opposite regulatory effects originate at the same location on the enzyme, or are transmitted by the same mechanism between the subunits, or both."}
{"id": "PMID:4458", "title": "Physical and kinetic properties of homogenous bovine lens aldose reductase.", "content": "Aldose reductase from calf lens was purified 15,000-fold. The homogeneity of the final preparation was demonstrated by molecular sieve chromatography, analytical ultracentrifugation, sodium dodecyl sulfate gel electrophoresis, Ouchterlony immunodiffusion, and polyacrylamide gel electrophoresis at three pH values. The monomeric nature of the enzyme is suggested by the molecular weight of 37,000 from both molecular sieve chromatography and sodium dodecyl sulfate-gel electrophoresis with beta-mercaptoethanol. This closely corresponds with a molecular weight of 40,400 estimated by using calculate physical constants in the Svedberg equation. The S20,w was 3.6 to 3.7 as determined from ultracentrifuge and sucrose density gradient data. The Stokes radius was found to be 2.5 +/- 0.2 nm and 2.75 +/- 0.15 nm by two different methods. The diffusion constant D20,w is (7.8 +/- 10(-7) +/- 0.45 X 10(-7) cm2/s). The molecule is nearly spherical as indicated by a frictional ratio f/fo = 1.14. The alpha-helical content was estimated from circular dichroism data to be 5% and did not change in the presence of added substrates, products, and some enzyme inhibitors. Homotropic cooperative effects were observed as shown by the concave downward curvature of the reciprocal plots.", "contents": "Physical and kinetic properties of homogenous bovine lens aldose reductase. Aldose reductase from calf lens was purified 15,000-fold. The homogeneity of the final preparation was demonstrated by molecular sieve chromatography, analytical ultracentrifugation, sodium dodecyl sulfate gel electrophoresis, Ouchterlony immunodiffusion, and polyacrylamide gel electrophoresis at three pH values. The monomeric nature of the enzyme is suggested by the molecular weight of 37,000 from both molecular sieve chromatography and sodium dodecyl sulfate-gel electrophoresis with beta-mercaptoethanol. This closely corresponds with a molecular weight of 40,400 estimated by using calculate physical constants in the Svedberg equation. The S20,w was 3.6 to 3.7 as determined from ultracentrifuge and sucrose density gradient data. The Stokes radius was found to be 2.5 +/- 0.2 nm and 2.75 +/- 0.15 nm by two different methods. The diffusion constant D20,w is (7.8 +/- 10(-7) +/- 0.45 X 10(-7) cm2/s). The molecule is nearly spherical as indicated by a frictional ratio f/fo = 1.14. The alpha-helical content was estimated from circular dichroism data to be 5% and did not change in the presence of added substrates, products, and some enzyme inhibitors. Homotropic cooperative effects were observed as shown by the concave downward curvature of the reciprocal plots."}
{"id": "PMID:4459", "title": "L-Asparaginase of Klebsiella aerogenes. Activation of its synthesis by glutamine synthetase.", "content": "An L-asparaginase has been purified some 250-fold from extracts of Klebsiella aerogenes to near homogeneity. The enzyme has a molecular weight of 141,000 as measured by gel filtration and appears to consist of four subunits of molecular weight 37,000. The enzyme has high affinity for L-asparagine, with a Km below 10(-5) M, and hydrolyzes glutamine at a 20-fold lower rate, with a Km of 10(-3) M. Interestingly, the enzyme exhibits marked gamma-glutamyltransferase activity but comparatively little beta-aspartyl-transferase activity. A mutant strain lacking this asparaginase has been isolated and grows at 1/2 to 1/3 the rate of the parent strain when asparagine is provided in the medium as the sole source of nitrogen. This strain grows as well as the wild type when the medium is supplemented with histidine or ammonia. Glutamine synthetase activates the formation of L-asparaginase. Mutants lacking glutamine synthetase fail to produce the asparaginase, and mutants with a high constitutive level of glutamine synthetase also contain the asparaginase at a high level. Thus, the formation of asparaginase is regulated in parallel with that of other enzymes capable of supplying the cell with ammonia or glutamate, such as histidase and proline oxidase. Formation of the asparaginase does not require induction by asparaginase and is not subject to catabolite repression.", "contents": "L-Asparaginase of Klebsiella aerogenes. Activation of its synthesis by glutamine synthetase. An L-asparaginase has been purified some 250-fold from extracts of Klebsiella aerogenes to near homogeneity. The enzyme has a molecular weight of 141,000 as measured by gel filtration and appears to consist of four subunits of molecular weight 37,000. The enzyme has high affinity for L-asparagine, with a Km below 10(-5) M, and hydrolyzes glutamine at a 20-fold lower rate, with a Km of 10(-3) M. Interestingly, the enzyme exhibits marked gamma-glutamyltransferase activity but comparatively little beta-aspartyl-transferase activity. A mutant strain lacking this asparaginase has been isolated and grows at 1/2 to 1/3 the rate of the parent strain when asparagine is provided in the medium as the sole source of nitrogen. This strain grows as well as the wild type when the medium is supplemented with histidine or ammonia. Glutamine synthetase activates the formation of L-asparaginase. Mutants lacking glutamine synthetase fail to produce the asparaginase, and mutants with a high constitutive level of glutamine synthetase also contain the asparaginase at a high level. Thus, the formation of asparaginase is regulated in parallel with that of other enzymes capable of supplying the cell with ammonia or glutamate, such as histidase and proline oxidase. Formation of the asparaginase does not require induction by asparaginase and is not subject to catabolite repression."}
{"id": "PMID:4460", "title": "Binding and degradation of insulin by human peripheral granulocytes. Demonstration of specific receptors with high affinity.", "content": "The interaction of insulin with human circulating granulocytes was studied with the use of 125I-insulin. Human granulocytes, isolated from blood by the B\u00f6yum technique, showed high insulin-degrading activity in vitro which almost obscured the presence of specific, high affinity binding sites. Degradation, measured by trichloroacetic acid precipitation and by binding to well characterized insulin receptors on cultured human lymphocytes (IM-9 line), was due to extracellular as well as cell-bound enzymes. Degradation was enhanced by Ca2+ and thiols and inhibited by various protease inhibitors and sulfhydryl-blocking reagents. Phenylmethylsulfonyl fluoride (5 X 10(-4) M), a serine protease inhibitor, was the most potent and inhibited 125I-insulin degradation by 80 to 90%. Tert-butyl hydroperoxide (2 X 10(-3) M), a glutathione-oxidizing reagent, inhibited degradation by 35 to 50%, possibly due to an effect on a glutathione-insulin transhydrogenase. Neither of the inhibitors affected cell viability. In the presence of inhibitors of degradation, binding sites for insulin with high affinity were detected, which by multiple criteria were true insulin receptors. Binding to these sites was rapid, saturable, and reversible with about 1000 sites/cell. The Hill coefficient for binding was 0.7, and the Scatchard plot of B/F versus B was curvilinear, due to site-site interactions of the negative cooperative type; the latter were demonstrated directly by kinetic studies. As shown previously for all other insulin receptors, binding was highly pH-dependent, and insulin analogues had affinities for these sites that closely correlated with their biological potencies.", "contents": "Binding and degradation of insulin by human peripheral granulocytes. Demonstration of specific receptors with high affinity. The interaction of insulin with human circulating granulocytes was studied with the use of 125I-insulin. Human granulocytes, isolated from blood by the B\u00f6yum technique, showed high insulin-degrading activity in vitro which almost obscured the presence of specific, high affinity binding sites. Degradation, measured by trichloroacetic acid precipitation and by binding to well characterized insulin receptors on cultured human lymphocytes (IM-9 line), was due to extracellular as well as cell-bound enzymes. Degradation was enhanced by Ca2+ and thiols and inhibited by various protease inhibitors and sulfhydryl-blocking reagents. Phenylmethylsulfonyl fluoride (5 X 10(-4) M), a serine protease inhibitor, was the most potent and inhibited 125I-insulin degradation by 80 to 90%. Tert-butyl hydroperoxide (2 X 10(-3) M), a glutathione-oxidizing reagent, inhibited degradation by 35 to 50%, possibly due to an effect on a glutathione-insulin transhydrogenase. Neither of the inhibitors affected cell viability. In the presence of inhibitors of degradation, binding sites for insulin with high affinity were detected, which by multiple criteria were true insulin receptors. Binding to these sites was rapid, saturable, and reversible with about 1000 sites/cell. The Hill coefficient for binding was 0.7, and the Scatchard plot of B/F versus B was curvilinear, due to site-site interactions of the negative cooperative type; the latter were demonstrated directly by kinetic studies. As shown previously for all other insulin receptors, binding was highly pH-dependent, and insulin analogues had affinities for these sites that closely correlated with their biological potencies."}
{"id": "PMID:4461", "title": "Triiodothyronine effects on some electrogenic properties of frog sartorius.", "content": "At 21 degrees C in vitro, 0.2 and 2.0 muM of triiodothyronine (T3) produced an increase in resting membrane potential (RMP) of Rana pipens sartorius when the pH of the external solution was 7.4. The RMP was increased by 2.0 muM T3 in the presence of 10(-4) and 10(-3) M ouabain but not in 10(-3) M of 2,4 dinitrophenol. Small increases in RMP were observed with 2.0 muM T3 in solutions with low external Na. At pH 7.1 0.2 muM T3 produced a small transient increase in RMP. Membrane resistance (Rm) was found to decline gradually during exposure to 0.2 muM at a pH of 7.4. Treatment with 2.0 muM T3 at pH 7.4 was accompanied by a transient reduction in Rm. Similar transient changes in Rm were produced by 0.2 and 2.0 muM T3 at pH of 7.1 T3 reduced membrane resistance in isotonic K2SO4 and tris-buffered Mn (20 mM) solutions indicating that T3 increases potassium permeability. Direct action potentials were studied at pH 7.1. Overshoot, amplitude and rate of rise of the action potential underwent a gradual decrease in the presence of 0.2 muM T3 while thresholds remained unchanged. Thresholds were increased during exposure to 2.0 muM T3 whereas overshoot, amplitude and rate of rise underwent transient decreases followed by a return toward control levels.", "contents": "Triiodothyronine effects on some electrogenic properties of frog sartorius. At 21 degrees C in vitro, 0.2 and 2.0 muM of triiodothyronine (T3) produced an increase in resting membrane potential (RMP) of Rana pipens sartorius when the pH of the external solution was 7.4. The RMP was increased by 2.0 muM T3 in the presence of 10(-4) and 10(-3) M ouabain but not in 10(-3) M of 2,4 dinitrophenol. Small increases in RMP were observed with 2.0 muM T3 in solutions with low external Na. At pH 7.1 0.2 muM T3 produced a small transient increase in RMP. Membrane resistance (Rm) was found to decline gradually during exposure to 0.2 muM at a pH of 7.4. Treatment with 2.0 muM T3 at pH 7.4 was accompanied by a transient reduction in Rm. Similar transient changes in Rm were produced by 0.2 and 2.0 muM T3 at pH of 7.1 T3 reduced membrane resistance in isotonic K2SO4 and tris-buffered Mn (20 mM) solutions indicating that T3 increases potassium permeability. Direct action potentials were studied at pH 7.1. Overshoot, amplitude and rate of rise of the action potential underwent a gradual decrease in the presence of 0.2 muM T3 while thresholds remained unchanged. Thresholds were increased during exposure to 2.0 muM T3 whereas overshoot, amplitude and rate of rise underwent transient decreases followed by a return toward control levels."}
{"id": "PMID:4462", "title": "[Acute amebic abscess of the liver followed by colonic ulcers. Report  of 2 cases].", "content": "Two unusual cases of ruptured acute amebic liver abcess are presented one with inferior vena caval compression. Surgical drainage was followed by the development of colonic complications (haemorrhage and perforation) although the patients were under specific therapy. After a new surgical operation both cases were cured. The relation with amebiasis is discussed. The possibility of such an association must always be kept in mind. The value of immunofluorescence test in the diagnosis is emphasised.", "contents": "[Acute amebic abscess of the liver followed by colonic ulcers. Report  of 2 cases]. Two unusual cases of ruptured acute amebic liver abcess are presented one with inferior vena caval compression. Surgical drainage was followed by the development of colonic complications (haemorrhage and perforation) although the patients were under specific therapy. After a new surgical operation both cases were cured. The relation with amebiasis is discussed. The possibility of such an association must always be kept in mind. The value of immunofluorescence test in the diagnosis is emphasised."}
{"id": "PMID:4463", "title": "High-performance ion-pair partition chromatography of sulfa drugs. Study and optimization of chemical parameters.", "content": "High-performance ion-pair partition chromatography is shown to be a versatile, efficient method for separating sulfonamides. For a group of fourteen sulfa drugs varying widely in pKA and hydrophobicity, the effect of mobile phase composition, counterion composition, pH, and ionic strength on their ion-pair partition chromatographic separation using tetrabutylammonium as the counterion and n-butanol-n-heptane as the mobile phase is shown. Wide variation in k' and a is possible by changing these parameters. Silica columns coated with buffered aqueous solutions of tetrabutylammonium sulfate resulted in efficiencies of 4000-6000 theoretical plates per 25 cm. These columns are stable for long periods of time, and can be stripped and re-used in the adsorption mode with little or no loss in efficiency. Several chromatograms are presented in order to illustrate the performance of ion-pair partition chromatography.", "contents": "High-performance ion-pair partition chromatography of sulfa drugs. Study and optimization of chemical parameters. High-performance ion-pair partition chromatography is shown to be a versatile, efficient method for separating sulfonamides. For a group of fourteen sulfa drugs varying widely in pKA and hydrophobicity, the effect of mobile phase composition, counterion composition, pH, and ionic strength on their ion-pair partition chromatographic separation using tetrabutylammonium as the counterion and n-butanol-n-heptane as the mobile phase is shown. Wide variation in k' and a is possible by changing these parameters. Silica columns coated with buffered aqueous solutions of tetrabutylammonium sulfate resulted in efficiencies of 4000-6000 theoretical plates per 25 cm. These columns are stable for long periods of time, and can be stripped and re-used in the adsorption mode with little or no loss in efficiency. Several chromatograms are presented in order to illustrate the performance of ion-pair partition chromatography."}
{"id": "PMID:4464", "title": "Gas chromatographic determination of carboxylic acid chlorides and residual carboxylic acid precursors used in the production of some penicillins.", "content": "An improved gas chromatographic method is described for the simultaneous determination of carboxylic acid chlorides and related carboxylic acids used in the production of some commercial semisynthetic penicillins. The acid chloride reacts with diethylamine to form the corresponding diethylamide. Carboxylic acid impurities are converted to trimethylsilyl esters. The two derivatives are separated and quantitated in the same chromatographic run. This method, an extension of the earlier procedure of Hishta and Bomstein (1), has been applied to the acid chlorides used to make oxacillin, cloxacillin, dicloxacillin, and methicillin (Figure 1); it shows promise of application to other acid chlorides. The determination is more selective than the usual titration methods, which do not differentiate among acids with similar pK's. Relative standard deviations of the acid chloride determination are 1.0-2.5%. Residual carboxylic acid can be repetitively determined within a range of 0.6% absolute.", "contents": "Gas chromatographic determination of carboxylic acid chlorides and residual carboxylic acid precursors used in the production of some penicillins. An improved gas chromatographic method is described for the simultaneous determination of carboxylic acid chlorides and related carboxylic acids used in the production of some commercial semisynthetic penicillins. The acid chloride reacts with diethylamine to form the corresponding diethylamide. Carboxylic acid impurities are converted to trimethylsilyl esters. The two derivatives are separated and quantitated in the same chromatographic run. This method, an extension of the earlier procedure of Hishta and Bomstein (1), has been applied to the acid chlorides used to make oxacillin, cloxacillin, dicloxacillin, and methicillin (Figure 1); it shows promise of application to other acid chlorides. The determination is more selective than the usual titration methods, which do not differentiate among acids with similar pK's. Relative standard deviations of the acid chloride determination are 1.0-2.5%. Residual carboxylic acid can be repetitively determined within a range of 0.6% absolute."}
{"id": "PMID:4465", "title": "Demonstration and some properties of cytosol-binding proteins for thyroxine and triiodothyronine in human liver.", "content": "Cytosol-binding proteins for L-thyroxine (T4) and triiodo-L-thyronine (T3) were studied in human liver specimens obtained at autopsy from 5 male and 2 female subjects. The liver cytosol containing 131I-T4 or T3, together with or without added stable hormones, was fractionated by Pevikon thin-layer electrophoresis at pH 8.6, 8.0, and7.4. It was demonstrated in all the specimens that besides a small amount of serum T4-binding globulin, there existed three T4-binding proteins, termed hT4-1, hT4-2 and hT4-3, with the electrophoretic mobilities of alpha2- and beta-globulins, and two T3-binding proteins, termed hT3-1 and hT3-2, with the mobilities of gamma-globulin. Binding of hormones by the cytosol proteins was pH-dependent, and a preliminary dialysis had no effect on the hormone binding. The major band of T4, hT4-2, bound more than half the tracer T4, and possessed the maximal binding capacity of 110 mug/100 ml of 33% cytosol at pH 7.4. However, it showed no apparent affinity for T3, because the bound T4 could not be displaced with a T3 load of 600 mug/100 ml. The major band of T3, hT3-2, bound more than 70% of the tracer T3, and appeared to have a large capacity for the hormone although secondary binding sites on the same molecule might be responsible for the large capacity. The binding sites appeared almost specific for T3, because only a small, insignificant displacement was noted with a T4 load of 600 mug/100 ml. The results provide evidence for distinct binding proteins for T4 and T3 in the human liver cytosol, though their physiological roles remain to be elucidated.", "contents": "Demonstration and some properties of cytosol-binding proteins for thyroxine and triiodothyronine in human liver. Cytosol-binding proteins for L-thyroxine (T4) and triiodo-L-thyronine (T3) were studied in human liver specimens obtained at autopsy from 5 male and 2 female subjects. The liver cytosol containing 131I-T4 or T3, together with or without added stable hormones, was fractionated by Pevikon thin-layer electrophoresis at pH 8.6, 8.0, and7.4. It was demonstrated in all the specimens that besides a small amount of serum T4-binding globulin, there existed three T4-binding proteins, termed hT4-1, hT4-2 and hT4-3, with the electrophoretic mobilities of alpha2- and beta-globulins, and two T3-binding proteins, termed hT3-1 and hT3-2, with the mobilities of gamma-globulin. Binding of hormones by the cytosol proteins was pH-dependent, and a preliminary dialysis had no effect on the hormone binding. The major band of T4, hT4-2, bound more than half the tracer T4, and possessed the maximal binding capacity of 110 mug/100 ml of 33% cytosol at pH 7.4. However, it showed no apparent affinity for T3, because the bound T4 could not be displaced with a T3 load of 600 mug/100 ml. The major band of T3, hT3-2, bound more than 70% of the tracer T3, and appeared to have a large capacity for the hormone although secondary binding sites on the same molecule might be responsible for the large capacity. The binding sites appeared almost specific for T3, because only a small, insignificant displacement was noted with a T4 load of 600 mug/100 ml. The results provide evidence for distinct binding proteins for T4 and T3 in the human liver cytosol, though their physiological roles remain to be elucidated."}
{"id": "PMID:4466", "title": "Glucagon-sensitive adenylate cyclase in human renal medulla.", "content": "In cell-free preparations (washed 600 x g pellets) of human renal medulla, glucagon produced a dose-dependent stimulation of adenylate cyclase. The stimulation of renal medullary adenylate cyclase by saturating concentrations of glucagon was additive to the saturating doses of vasopressin. Furthermore, L-isoproterenol stimulated renal medullary adenylate cyclase in a dose-dependent manner, and this stimulation was blocked by DL-propranolol. Stimulation of the renal medullary adenylate cyclase by maximal doses of glucagon and L-isoproterenol was additive. DL-Propranolol did not inhibit stimulation of glucagon. Thus, the results indicate the existence of a specific adenylate cyclase that is responsive to glucagon--distinct from the isoproterenol-sensitive adenylate cyclase and the previously described vasopressin-sensitive adenylate cyclase in human renal medulla. We suggest that the renal tubular effect of glucagon may be mediated by glucagon-dependent cyclic-AMP production in renal tissue.", "contents": "Glucagon-sensitive adenylate cyclase in human renal medulla. In cell-free preparations (washed 600 x g pellets) of human renal medulla, glucagon produced a dose-dependent stimulation of adenylate cyclase. The stimulation of renal medullary adenylate cyclase by saturating concentrations of glucagon was additive to the saturating doses of vasopressin. Furthermore, L-isoproterenol stimulated renal medullary adenylate cyclase in a dose-dependent manner, and this stimulation was blocked by DL-propranolol. Stimulation of the renal medullary adenylate cyclase by maximal doses of glucagon and L-isoproterenol was additive. DL-Propranolol did not inhibit stimulation of glucagon. Thus, the results indicate the existence of a specific adenylate cyclase that is responsive to glucagon--distinct from the isoproterenol-sensitive adenylate cyclase and the previously described vasopressin-sensitive adenylate cyclase in human renal medulla. We suggest that the renal tubular effect of glucagon may be mediated by glucagon-dependent cyclic-AMP production in renal tissue."}
{"id": "PMID:4467", "title": "Simultaneous comparison of delta 5-3beta-hydroxysteroid levels in the fetoplacental circulation of normal pregnancy in labor and not in labor.", "content": "Concentrations of pregnenolone (delta5P), dehydroepiandrosterone (DHEA), 16alpha-hydroxydehydroepiandrosterone (16alpha-OH DHEA), pregnenolone sulfate (delta5P-S), and dehydroepiandrosterone sulfate (DHEA-S) were measured simultaneously by radioimmunoassay in individual, paired umbilical artery (UA) and vein (UV) sera from 18 normal term pregnancies, 6 in labor, 12 not in labor. Mean UA and UV levels +/- SEM (ng/ml) were for delta5P: 30.39 +/- 1.69, 35.55 +/- 3.06; DHEA: 12.31 +/- 2.34, 3.66 +/- 0.38; 16alpha-OH DHEA: 7.48 +/- 0.63, 10.59 +/- 0.78; delta5P-S: 1,652 +/- 154, 1,486 +/- 130; DHEA-S: 2,122 +/- 134, +/- 134, 1,906 +/- 134. Umbilical artery delta5P-S, DHEA-S, and DHEA levels were significantly higher than UV levels, whereas the reverse was true for delta5P and 16alpha-OH DHEA. The inverse arterio-venous (A-V) gradient for 16alpha-OH DHEA was contrary to previous published reports using pooled samples. Comparison by linear regression of paired UA and UV steroid concentrations of delta5P, delta5P-S, DHEA, and DHEA-S revealed a significant correlation (P less than 0.01) for each steroid. Labor was associated with a significant increase in UA levels of DHEA-S and a smaller, but not quite significant, increase in UA levels of delta5P-S, while similar changes for unconjugated delta5-3beta-hydroxysteroids were not observed. Mean A-V gradients between the group of patients in labor and those not in labor were not significantly different. These data demonstrate that: 1) a significant difference between UA and UV concentrations exists for delta5P, DHEA, 16alpha-OH DHEA, delta5P-S, and DHEA-S; 2) there is a significant correlation between UA and UV concentrations for delta5P, DHEA, delta5P-S, and DHEA-S, implying that each fetoplacental unit maintains an equilibrium relative to these steroid concentrations in the umbilical circulation; 3) labor is associated with a significant increase in UA levels of DHEA-S and probably of delta5P-S.", "contents": "Simultaneous comparison of delta 5-3beta-hydroxysteroid levels in the fetoplacental circulation of normal pregnancy in labor and not in labor. Concentrations of pregnenolone (delta5P), dehydroepiandrosterone (DHEA), 16alpha-hydroxydehydroepiandrosterone (16alpha-OH DHEA), pregnenolone sulfate (delta5P-S), and dehydroepiandrosterone sulfate (DHEA-S) were measured simultaneously by radioimmunoassay in individual, paired umbilical artery (UA) and vein (UV) sera from 18 normal term pregnancies, 6 in labor, 12 not in labor. Mean UA and UV levels +/- SEM (ng/ml) were for delta5P: 30.39 +/- 1.69, 35.55 +/- 3.06; DHEA: 12.31 +/- 2.34, 3.66 +/- 0.38; 16alpha-OH DHEA: 7.48 +/- 0.63, 10.59 +/- 0.78; delta5P-S: 1,652 +/- 154, 1,486 +/- 130; DHEA-S: 2,122 +/- 134, +/- 134, 1,906 +/- 134. Umbilical artery delta5P-S, DHEA-S, and DHEA levels were significantly higher than UV levels, whereas the reverse was true for delta5P and 16alpha-OH DHEA. The inverse arterio-venous (A-V) gradient for 16alpha-OH DHEA was contrary to previous published reports using pooled samples. Comparison by linear regression of paired UA and UV steroid concentrations of delta5P, delta5P-S, DHEA, and DHEA-S revealed a significant correlation (P less than 0.01) for each steroid. Labor was associated with a significant increase in UA levels of DHEA-S and a smaller, but not quite significant, increase in UA levels of delta5P-S, while similar changes for unconjugated delta5-3beta-hydroxysteroids were not observed. Mean A-V gradients between the group of patients in labor and those not in labor were not significantly different. These data demonstrate that: 1) a significant difference between UA and UV concentrations exists for delta5P, DHEA, 16alpha-OH DHEA, delta5P-S, and DHEA-S; 2) there is a significant correlation between UA and UV concentrations for delta5P, DHEA, delta5P-S, and DHEA-S, implying that each fetoplacental unit maintains an equilibrium relative to these steroid concentrations in the umbilical circulation; 3) labor is associated with a significant increase in UA levels of DHEA-S and probably of delta5P-S."}
{"id": "PMID:4468", "title": "Isolation of human eosinophil phospholipase D.", "content": "Phospholipase D preferentially contained in human eosinophil polymorphonuclear leukocytes as compared to other leukocytes was isolated by sequential asion and cation exchange chromatography and gel filtration. The purified eosinophil enzyme specifically liberated choline from I-alpha-phosphatidyl choline with a pH optimum of 4.5-6.0 and exhibited a pI of 5.8-6.2 on polyacrylamide-gel isoelectric focusing, which are properties shared by phospholipase D from plant sources; however, its apparent mol wt of 60,000 is approximately one-half that of the plant enzymes. Eosinophil and cabbage phospholipase D inactivated a partially purified rat platelet-activating factor (PAF) in a time- and dose-dependent reaction. The cleavage of this PAF activity was attributed to the inherent phospholipase D activity of the eosinophil enzyme since the two activities chromatographed together at each purification step, and there was apparent reciprocal inhibition of choline-generating activity by PAF and of PAF-inactivating activity by phosphatidyl choline. Thus, possible regulatory functions of the eosinophil in immediate hypersensitivity reactions include inactivation of a PAF by phospholipase D as well as degradation of slow-reacting substance of anaphylaxis by arylsulfatase B.", "contents": "Isolation of human eosinophil phospholipase D. Phospholipase D preferentially contained in human eosinophil polymorphonuclear leukocytes as compared to other leukocytes was isolated by sequential asion and cation exchange chromatography and gel filtration. The purified eosinophil enzyme specifically liberated choline from I-alpha-phosphatidyl choline with a pH optimum of 4.5-6.0 and exhibited a pI of 5.8-6.2 on polyacrylamide-gel isoelectric focusing, which are properties shared by phospholipase D from plant sources; however, its apparent mol wt of 60,000 is approximately one-half that of the plant enzymes. Eosinophil and cabbage phospholipase D inactivated a partially purified rat platelet-activating factor (PAF) in a time- and dose-dependent reaction. The cleavage of this PAF activity was attributed to the inherent phospholipase D activity of the eosinophil enzyme since the two activities chromatographed together at each purification step, and there was apparent reciprocal inhibition of choline-generating activity by PAF and of PAF-inactivating activity by phosphatidyl choline. Thus, possible regulatory functions of the eosinophil in immediate hypersensitivity reactions include inactivation of a PAF by phospholipase D as well as degradation of slow-reacting substance of anaphylaxis by arylsulfatase B."}
{"id": "PMID:4469", "title": "Role of expectancy set in the systematic desensitization of speech anxiety: an extension of prior research.", "content": "The influence of expectancy set with regard to therapy outcome on the effectiveness of systematic desensitization (SD) for reducing public speaking anxiety was investigated. The 7 Ss given a high expectancy set for favorable therapy outcome were informed about psychological research that indicates that SD is effective to reduce public speaking fears. SD was administered with the standard instructions to the 11 Ss given a neutral expectancy set. This expectancy manipulation did not require deception and perhaps could be used with actual SD therapy clients. As in previous research by Woy and Efran, the expectancy set manipulation significantly modified Ss' self-report of subjective perceptions of anxiety from pretreatment to posttreatment speeches, but did not affect overt behavioral or physiological indices of anxiety. Since subjective perceptions of anxiety responses are psychologically significant behaviors, these data suggest the importance of conveying a high expectation of improvement to SD and perhaps also to other types of therapy clients. SD sessions administered to small groups of clients on consecutive days, as in this study, appeared to be as effective to reduce speech anxiety as SD sessions administered to each client individually at 1-week intervals, as in the Woy and Efran study.", "contents": "Role of expectancy set in the systematic desensitization of speech anxiety: an extension of prior research. The influence of expectancy set with regard to therapy outcome on the effectiveness of systematic desensitization (SD) for reducing public speaking anxiety was investigated. The 7 Ss given a high expectancy set for favorable therapy outcome were informed about psychological research that indicates that SD is effective to reduce public speaking fears. SD was administered with the standard instructions to the 11 Ss given a neutral expectancy set. This expectancy manipulation did not require deception and perhaps could be used with actual SD therapy clients. As in previous research by Woy and Efran, the expectancy set manipulation significantly modified Ss' self-report of subjective perceptions of anxiety from pretreatment to posttreatment speeches, but did not affect overt behavioral or physiological indices of anxiety. Since subjective perceptions of anxiety responses are psychologically significant behaviors, these data suggest the importance of conveying a high expectation of improvement to SD and perhaps also to other types of therapy clients. SD sessions administered to small groups of clients on consecutive days, as in this study, appeared to be as effective to reduce speech anxiety as SD sessions administered to each client individually at 1-week intervals, as in the Woy and Efran study."}
{"id": "PMID:4470", "title": "Graduated approach modeling in an aversive task.", "content": "Sixty female Ss were assigned randomly to six conditions that involved self-administration of electrical shock. These were: (1) no model-one trial S response; (2) no model-graduated trial S response; (3) one trial model-one trial S response; (4) one trial model-graduated S response; (5) graduated model-one trial response; and (6) graduated model-graduated response. Results indicated that graduated exposure of S to an aversive stimuli was more effective than a single such exposure and that type of exposure provided by a model had little effect.", "contents": "Graduated approach modeling in an aversive task. Sixty female Ss were assigned randomly to six conditions that involved self-administration of electrical shock. These were: (1) no model-one trial S response; (2) no model-graduated trial S response; (3) one trial model-one trial S response; (4) one trial model-graduated S response; (5) graduated model-one trial response; and (6) graduated model-graduated response. Results indicated that graduated exposure of S to an aversive stimuli was more effective than a single such exposure and that type of exposure provided by a model had little effect."}
{"id": "PMID:4471", "title": "Cephradine excretion in humans with pH-altered urine.", "content": "In a random crossover study, ten healthy men were pretreated with ammonium chloride or sodium bicarbonate to alter urinary pH, and then were given a single 1-Gm dose of cephradine, either orally or intravenously. No significant changes were found in the terminal phase rate constant nor in the time or magnitude of peak concentration. Total recovery was greater than 90 per cent whenever degradation of cephradine did not occur. An unexplained but significant reduction in area under curve was present in data for prealkalinized subjects and for all subjects who took cephradine orally. Trapping of cephradine was not significant in the excretory pathway.", "contents": "Cephradine excretion in humans with pH-altered urine. In a random crossover study, ten healthy men were pretreated with ammonium chloride or sodium bicarbonate to alter urinary pH, and then were given a single 1-Gm dose of cephradine, either orally or intravenously. No significant changes were found in the terminal phase rate constant nor in the time or magnitude of peak concentration. Total recovery was greater than 90 per cent whenever degradation of cephradine did not occur. An unexplained but significant reduction in area under curve was present in data for prealkalinized subjects and for all subjects who took cephradine orally. Trapping of cephradine was not significant in the excretory pathway."}
{"id": "PMID:4472", "title": "Partial agonist properties and toxicity of oral oxilorphan.", "content": "Alternative pharmacologic adjuncts are needed for the management of opiate abuse. Oxilorphan, a narcotic antagonist, was studied at 5 different dose levels (1, 2, 4, 6, and 8 mg) in 30 normal subjects to determine the relation of single oral doses and toxicity. The drug causes pupillary constriction and mild central nervous system side effects (nausea, dizziness) at all doses. Mean urine volume increased (P less than 0.05) during the 12 hours after 1 and 2 mg. Oxilorphan has partial agonist properties similar to dl-cyclazocine.", "contents": "Partial agonist properties and toxicity of oral oxilorphan. Alternative pharmacologic adjuncts are needed for the management of opiate abuse. Oxilorphan, a narcotic antagonist, was studied at 5 different dose levels (1, 2, 4, 6, and 8 mg) in 30 normal subjects to determine the relation of single oral doses and toxicity. The drug causes pupillary constriction and mild central nervous system side effects (nausea, dizziness) at all doses. Mean urine volume increased (P less than 0.05) during the 12 hours after 1 and 2 mg. Oxilorphan has partial agonist properties similar to dl-cyclazocine."}
{"id": "PMID:4474", "title": "Characteristics of the release of adenosine 3':5'-monophosphate from micropipets by microiontophoresis.", "content": "The transfer number for radio-labelled cyclic AMP released from microiontophoretic pipets into brain pieces was determined for a large number of samples by radioassay. Release of cyclic AMP was linearly related to both iontophoretic current intensity and time as predicted by Faraday's Law. The results revealed that cyclic AMP has a rather low transfer number. In addition, an unusually large amount of variation of release, both within and among pipets was found under a variety of times and currents. The cause of the variation is not known but could be due to the unusual structure of the cyclic AMP molecule and the fact that it must be iontophoresed as a negative ion. These characteristics of cyclic AMP release may contribute to the difficulty in obtaining positive responses from appropriate neuronal target cells in vivo.", "contents": "Characteristics of the release of adenosine 3':5'-monophosphate from micropipets by microiontophoresis. The transfer number for radio-labelled cyclic AMP released from microiontophoretic pipets into brain pieces was determined for a large number of samples by radioassay. Release of cyclic AMP was linearly related to both iontophoretic current intensity and time as predicted by Faraday's Law. The results revealed that cyclic AMP has a rather low transfer number. In addition, an unusually large amount of variation of release, both within and among pipets was found under a variety of times and currents. The cause of the variation is not known but could be due to the unusual structure of the cyclic AMP molecule and the fact that it must be iontophoresed as a negative ion. These characteristics of cyclic AMP release may contribute to the difficulty in obtaining positive responses from appropriate neuronal target cells in vivo."}
{"id": "PMID:4475", "title": "Effects of egg factors on cyclic nucleotide metabolism in sea urchin sperm.", "content": "Cyclic AMP in Strongylocentrotus purpuratus sperm was elevated approximately 2-fold by theophylline or 1-methyl-3-isobutylxanthine. Factors released from sea urchin eggs (FRE) elevated sperm cyclic AMP by about 7-fold within 1 min, and the combination of FRE with theophylline increased sperm cyclic AMP up to 100-fold within 1 min. Cyclic GMP in sea urchin sperm was slightly elevated by theophylline, but was lowered by FRE. Cyclic GMP in sperm treated with FRE plus theophylline was not higher than in sperm treated with theophylline alone. The ability of FRE-containing sea water to increase sperm cyclic AMP in the presence of theophylline was altered only slightly if at all by boiling, but it was decreased by about 50% by dialysis and destroyed by ashing. Filtration of FRE on Sephadex G-50 columns yielded two peaks of cyclic AMP-elevating activity. One peak (peak I) was eluted at the column void volume, and the other (peak II) was retained by the column. The cyclic GMP-lowering activity was located in fractions approximately corresponding to peak I of cyclic AMP-elevating activity. Dialysis of FRE-containing sea water before its application to the G-50 column virtually eliminated peak II of the cyclic AMP-elevating activity. When the cyclic AMP-elevating activity in peak I was filtered on Bio Gel A-5m columns, it also migrated at or near the column void volume. Fractions corresponding to peak I contained material that inhibited both guanylate and adenylate cyclase activities in broken cell preparations of sperm and guanylate cyclase from rat lung. The inhibitory material was stable to boiling, non-dialyzable, and destroyed by ashing. Under a variety of conditions, FRE-containing sea water or cyclic AMP-elevating peaks I or II did not stimulate sperm adenylate cyclase activity in broken cell preparations.", "contents": "Effects of egg factors on cyclic nucleotide metabolism in sea urchin sperm. Cyclic AMP in Strongylocentrotus purpuratus sperm was elevated approximately 2-fold by theophylline or 1-methyl-3-isobutylxanthine. Factors released from sea urchin eggs (FRE) elevated sperm cyclic AMP by about 7-fold within 1 min, and the combination of FRE with theophylline increased sperm cyclic AMP up to 100-fold within 1 min. Cyclic GMP in sea urchin sperm was slightly elevated by theophylline, but was lowered by FRE. Cyclic GMP in sperm treated with FRE plus theophylline was not higher than in sperm treated with theophylline alone. The ability of FRE-containing sea water to increase sperm cyclic AMP in the presence of theophylline was altered only slightly if at all by boiling, but it was decreased by about 50% by dialysis and destroyed by ashing. Filtration of FRE on Sephadex G-50 columns yielded two peaks of cyclic AMP-elevating activity. One peak (peak I) was eluted at the column void volume, and the other (peak II) was retained by the column. The cyclic GMP-lowering activity was located in fractions approximately corresponding to peak I of cyclic AMP-elevating activity. Dialysis of FRE-containing sea water before its application to the G-50 column virtually eliminated peak II of the cyclic AMP-elevating activity. When the cyclic AMP-elevating activity in peak I was filtered on Bio Gel A-5m columns, it also migrated at or near the column void volume. Fractions corresponding to peak I contained material that inhibited both guanylate and adenylate cyclase activities in broken cell preparations of sperm and guanylate cyclase from rat lung. The inhibitory material was stable to boiling, non-dialyzable, and destroyed by ashing. Under a variety of conditions, FRE-containing sea water or cyclic AMP-elevating peaks I or II did not stimulate sperm adenylate cyclase activity in broken cell preparations."}
{"id": "PMID:4476", "title": "Dephosphorylation of bovine casein by milk alkaline phosphatase.", "content": "The pH of optimum activity of alkaline phosphatase from cow's milk depended on the substrate, being 10-1 for rho-nitrophenylphosphate, 8-6 for phosphoserine, 8-0 for phosvitin and 6-8 for casein. Individual casein components were dephosphorylated more rapidly than mixtures of alphas- and beta-caseins or of alphas-, beta-and kappa-caseins and micellar casein. Mixtures of 2 components involving kappa-casein were more readily dephosphorylated than alphas- and beta-casein mixtures. At pH 6-8, lactose, whey proteins and phosphate ions had an inhibitory effect. beta-Lactoglobulin had an inhibitory effect only when the pH of the reaction was lower than the optimum pH value of the enzyme. Mg2+ and Zn2+ were not inhibitory. The optimum conditions for dephosphorylation of casein are described.", "contents": "Dephosphorylation of bovine casein by milk alkaline phosphatase. The pH of optimum activity of alkaline phosphatase from cow's milk depended on the substrate, being 10-1 for rho-nitrophenylphosphate, 8-6 for phosphoserine, 8-0 for phosvitin and 6-8 for casein. Individual casein components were dephosphorylated more rapidly than mixtures of alphas- and beta-caseins or of alphas-, beta-and kappa-caseins and micellar casein. Mixtures of 2 components involving kappa-casein were more readily dephosphorylated than alphas- and beta-casein mixtures. At pH 6-8, lactose, whey proteins and phosphate ions had an inhibitory effect. beta-Lactoglobulin had an inhibitory effect only when the pH of the reaction was lower than the optimum pH value of the enzyme. Mg2+ and Zn2+ were not inhibitory. The optimum conditions for dephosphorylation of casein are described."}
{"id": "PMID:4473", "title": "Effect of flurazepam on common clinical laboratory tests.", "content": "Twenty-two clinical laboratory tests performed on blood samples from 16 normal subjects following one week of either flurazepam or placebo administered in a double-blind method showed no apparent chemical interference by flurazepam on any of the testing procedures.", "contents": "Effect of flurazepam on common clinical laboratory tests. Twenty-two clinical laboratory tests performed on blood samples from 16 normal subjects following one week of either flurazepam or placebo administered in a double-blind method showed no apparent chemical interference by flurazepam on any of the testing procedures."}
{"id": "PMID:4477", "title": "A kinetic concepto of lipid transport in ruminants.", "content": "Summarization of the literature shows a strong correlation between dietary fatty acid intake and total lipid concentration in plasma in lactating cows whereas total milk fat secreted is related to neither of these. In the process of plasma triglyceride removal, chylomicra and very low density lipoproteins are converted to low density lipoproteins. Limited kinetic data indicate that the fractional removal rates for chulomicra and very low density lipoproteins are rapid in lactating cows whereas fractional removal of low density lipoproteins is slower, resulting in accumulation of the latter in plasma. Under such conditions, low density lipoprotein concentrations of plasma would not be expected to reflect quantitatively the transfer of plasma triglyceride fatty acids to milk fat. Quantitative analysis or triglyceride fatty acid turnover in density less than 1.006 lipoproteins should delineate the role of plasma lipid transport in milk fat synthesis. High fat diets protected from rumen biohydrogenation have proven to be a useful approach in studying ruminant fat metabolism and may be used more extensively to elucidate the role of cholesterol in plasma lipid transport and the metabolism of essential fatty acids in ruminants.", "contents": "A kinetic concepto of lipid transport in ruminants. Summarization of the literature shows a strong correlation between dietary fatty acid intake and total lipid concentration in plasma in lactating cows whereas total milk fat secreted is related to neither of these. In the process of plasma triglyceride removal, chylomicra and very low density lipoproteins are converted to low density lipoproteins. Limited kinetic data indicate that the fractional removal rates for chulomicra and very low density lipoproteins are rapid in lactating cows whereas fractional removal of low density lipoproteins is slower, resulting in accumulation of the latter in plasma. Under such conditions, low density lipoprotein concentrations of plasma would not be expected to reflect quantitatively the transfer of plasma triglyceride fatty acids to milk fat. Quantitative analysis or triglyceride fatty acid turnover in density less than 1.006 lipoproteins should delineate the role of plasma lipid transport in milk fat synthesis. High fat diets protected from rumen biohydrogenation have proven to be a useful approach in studying ruminant fat metabolism and may be used more extensively to elucidate the role of cholesterol in plasma lipid transport and the metabolism of essential fatty acids in ruminants."}
{"id": "PMID:4478", "title": "Bovine pancreatic lipase.I.Isolation, homogeneity, and characterization.", "content": "Bovine pancreatic lipase was isolated in pure form by lyophilization of fresh bovine pancreas, extraction of the enzyme with sucrose solution, fractional precipitation with ammonium sulfate and acetone, followed by chromatography on Sephadex G-100. The specific activity of the purest lipase fraction was 1750 micromoles fatty acid, liberated in 30 min per milligram of protein, indicating a purification of approximately 473-fold, with an overall yield of about 42%. Homogeneity of the enzyme was confirmed by rechromatography on Sephadex G-100 as well as with the gel electrophoretic and ultracentrifugal techniques. The purified enzyme gave a typical protein ultraviolet absorption spectrum with maximum absorption at 276 nm and minimum at 252 nm. The purified enzyme exhibited a single pH optimum of 8.8 and an isoelectric point near pH 5.5. Its optimum temperature was 37 C, and its optimum substrate concentration was 10%. These properties resembled those of milk lipase.", "contents": "Bovine pancreatic lipase.I.Isolation, homogeneity, and characterization. Bovine pancreatic lipase was isolated in pure form by lyophilization of fresh bovine pancreas, extraction of the enzyme with sucrose solution, fractional precipitation with ammonium sulfate and acetone, followed by chromatography on Sephadex G-100. The specific activity of the purest lipase fraction was 1750 micromoles fatty acid, liberated in 30 min per milligram of protein, indicating a purification of approximately 473-fold, with an overall yield of about 42%. Homogeneity of the enzyme was confirmed by rechromatography on Sephadex G-100 as well as with the gel electrophoretic and ultracentrifugal techniques. The purified enzyme gave a typical protein ultraviolet absorption spectrum with maximum absorption at 276 nm and minimum at 252 nm. The purified enzyme exhibited a single pH optimum of 8.8 and an isoelectric point near pH 5.5. Its optimum temperature was 37 C, and its optimum substrate concentration was 10%. These properties resembled those of milk lipase."}
{"id": "PMID:4479", "title": "Distribution and removal of cadmium from milk.", "content": "Distribution of added cadmium in milk systems and the feasibility of removing cadmium were investigated. In milk containing 1 ppm cadmium, 96% of the added cadmium chloride was dispersed in the skim milk fraction, and 3% was associated with the cream fraction. Cadmium was not bound strongly to any protein fraction. The association of cadmium with acid casein, whey proteins, and the fat globule membrane was 18,6, and .5% of total added cadmium. With a 5-min exposure thiosuccinylated amino-ethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced human hair removed 72, 70, and 30%, respectively, of added cadmium in skim milk previously equilibrated for 2 h at 37 C. Increasing equilibration time beyond 24 h had no effect on removal efficiency whereas increasing pH decreased cadmium removal markedly.", "contents": "Distribution and removal of cadmium from milk. Distribution of added cadmium in milk systems and the feasibility of removing cadmium were investigated. In milk containing 1 ppm cadmium, 96% of the added cadmium chloride was dispersed in the skim milk fraction, and 3% was associated with the cream fraction. Cadmium was not bound strongly to any protein fraction. The association of cadmium with acid casein, whey proteins, and the fat globule membrane was 18,6, and .5% of total added cadmium. With a 5-min exposure thiosuccinylated amino-ethyl cellulose, thionitrocarboxyphenylated aminoethyl cellulose, and reduced human hair removed 72, 70, and 30%, respectively, of added cadmium in skim milk previously equilibrated for 2 h at 37 C. Increasing equilibration time beyond 24 h had no effect on removal efficiency whereas increasing pH decreased cadmium removal markedly."}
{"id": "PMID:4480", "title": "Influence of viable yogurt microflora on digestion of lactose by the rat.", "content": "Laboratory rats were fed experimental diets including yogurt, pasteurized yogurt, and simulated yogurt with sucrose or lactose for 7 days followed by a single experimental meal of yogurt, pasteurized yogurt, or simulated yogurt. Assays of blood galactose demonstrated that animals fed natural yogurt containing the viable culture microflora were able to absorb galactose more efficiently. Intestinal lactase activity of yogurt-fed animals was greater than in animals fed other experimental diets including pasteurized yogurt. Gastrointestinal survival of culture organisms was demonstrated in vivo up to 3 h after feeding, and thus, the viable cells resulted in more efficient hydrolysis which favored lactose digestion in natural yogurt.", "contents": "Influence of viable yogurt microflora on digestion of lactose by the rat. Laboratory rats were fed experimental diets including yogurt, pasteurized yogurt, and simulated yogurt with sucrose or lactose for 7 days followed by a single experimental meal of yogurt, pasteurized yogurt, or simulated yogurt. Assays of blood galactose demonstrated that animals fed natural yogurt containing the viable culture microflora were able to absorb galactose more efficiently. Intestinal lactase activity of yogurt-fed animals was greater than in animals fed other experimental diets including pasteurized yogurt. Gastrointestinal survival of culture organisms was demonstrated in vivo up to 3 h after feeding, and thus, the viable cells resulted in more efficient hydrolysis which favored lactose digestion in natural yogurt."}
{"id": "PMID:4481", "title": "Nonimmunologic aspects of caries resistance.", "content": "A variety of components provide salivary secretions with an array of potentially effective means of combating cariogenic challenges. These defense factors range from a laissez-faire mechanical cleansing to exquisitely controlled production of highly specific antibodies. In between the two extremes are antibacterial systems whose operating characteristics are only beginning to be understood. These systems are well worth our attention. They may be the key to our understanding of variations in individual susceptibility, and could provide valuable leads for development of anticaries agents.", "contents": "Nonimmunologic aspects of caries resistance. A variety of components provide salivary secretions with an array of potentially effective means of combating cariogenic challenges. These defense factors range from a laissez-faire mechanical cleansing to exquisitely controlled production of highly specific antibodies. In between the two extremes are antibacterial systems whose operating characteristics are only beginning to be understood. These systems are well worth our attention. They may be the key to our understanding of variations in individual susceptibility, and could provide valuable leads for development of anticaries agents."}
{"id": "PMID:4482", "title": "Adherence of serotype e Streptococcus mutans and the inhibitory effect of Lancefield group E and S mutans type e antiserum.", "content": "S mutans strain MT703 from an active carious lesion in the tooth of a child had type e specificity and showed a cross-reaction with the Lancefield group E cell wall streptococcal polysaccharide antigen. Heat-killed cells MT703 adhered to a glass surface in the presence of CGT MT703 and sucrose. Pretreatment of the cells with anti-MT703 whole cell serums inhibited adherecne. The removal of glycerol teichoic acid antibody and group E antibody from the MT703 serum did not result in a loss of inhibitory activity. Antiserum with or without adsorption significantly inhibited glucan synthesis by CGT from sucrose. Antibodies specific for the polyglycerol phosphate of teichoic acid did not inhibit adherence. Anti-group E serum and serums specific for other types of S mutans, did not show adherence inhibitory activity except for an occasional type c specific antiserum. Antibody specific for the type e antigen produced significant inhibition of the binding of CGT to the MT703 cell wall, and adherence of these cells did not occur. Antibody to CGT inhibited glucan synthesis. Treatment of the cells with dextranase, dextran antibody, or trypsin caused a significant reduction in adherence. The results suggest that the type antigen and dextran on the surface of the S mutans type e cell are functional in adherence, and that these polymers are associated with cell wall protein.", "contents": "Adherence of serotype e Streptococcus mutans and the inhibitory effect of Lancefield group E and S mutans type e antiserum. S mutans strain MT703 from an active carious lesion in the tooth of a child had type e specificity and showed a cross-reaction with the Lancefield group E cell wall streptococcal polysaccharide antigen. Heat-killed cells MT703 adhered to a glass surface in the presence of CGT MT703 and sucrose. Pretreatment of the cells with anti-MT703 whole cell serums inhibited adherecne. The removal of glycerol teichoic acid antibody and group E antibody from the MT703 serum did not result in a loss of inhibitory activity. Antiserum with or without adsorption significantly inhibited glucan synthesis by CGT from sucrose. Antibodies specific for the polyglycerol phosphate of teichoic acid did not inhibit adherence. Anti-group E serum and serums specific for other types of S mutans, did not show adherence inhibitory activity except for an occasional type c specific antiserum. Antibody specific for the type e antigen produced significant inhibition of the binding of CGT to the MT703 cell wall, and adherence of these cells did not occur. Antibody to CGT inhibited glucan synthesis. Treatment of the cells with dextranase, dextran antibody, or trypsin caused a significant reduction in adherence. The results suggest that the type antigen and dextran on the surface of the S mutans type e cell are functional in adherence, and that these polymers are associated with cell wall protein."}
{"id": "PMID:4483", "title": "The effect of beta adrenergic blockade on bronchial sensitivity to acetyl-beta-methacholine in normal and allergic rhinitis subjects.", "content": "The effect of propranolol inhalation on sensitivity to methacholine inhalation was studied in normal and allergic rhinitis subjects to determine whether beta adrenergic blockade alters sensitivity to mediators in nonasthmatic atopic individuals. A partial beta adrenergic blockade is suggested as being instrumental in asthma. Hay fever patients studied showed similar effects and also developed asthma for the first time.", "contents": "The effect of beta adrenergic blockade on bronchial sensitivity to acetyl-beta-methacholine in normal and allergic rhinitis subjects. The effect of propranolol inhalation on sensitivity to methacholine inhalation was studied in normal and allergic rhinitis subjects to determine whether beta adrenergic blockade alters sensitivity to mediators in nonasthmatic atopic individuals. A partial beta adrenergic blockade is suggested as being instrumental in asthma. Hay fever patients studied showed similar effects and also developed asthma for the first time."}
{"id": "PMID:4484", "title": "Effect of beta adrenergic stimulation and blockade on cutaneous reactivity to histamine.", "content": "It has been previously demonstrated that iontophoresis of beta adrenergic agents will alter the size of immediate hypersensitivity skin tests. It was unclear whether this alteration was due to an effect on the dermal mast cell (inhibition of histamine release) or on the cutaneous vasculature (inhibition of capillary permeability). For this reason isoproterenol, propranolol, diphenhydramine as a positive control, and saline as a negative control were iontophoresed onto the forearm of 10 atopic and 10 nonatopic adult subjects. In order to bypass histamine release from mast cells the patients were then challenged directly with histamine by the \"prick\" technique. The size of the resultant wheals was noted. The data obtained allowed the following conclusions: (1) The atopic group responded to histamine with greater wheal size than the nonatopic group. (2) Iontophoresis of diphyenhydramine effectively reduced the magnitude of the histamine wheal in both groups. (3) Isoproterenol decreased the wheal size in both groups. (4) Propranolol increased the wheal size in only the nonatopic group. (5) The successful modulation of the histamine-induced wheal and flare indicated that these drugs, regardless of their effect on the dermal mast cell, exert a measurable effect on the target organ (vasculature).", "contents": "Effect of beta adrenergic stimulation and blockade on cutaneous reactivity to histamine. It has been previously demonstrated that iontophoresis of beta adrenergic agents will alter the size of immediate hypersensitivity skin tests. It was unclear whether this alteration was due to an effect on the dermal mast cell (inhibition of histamine release) or on the cutaneous vasculature (inhibition of capillary permeability). For this reason isoproterenol, propranolol, diphenhydramine as a positive control, and saline as a negative control were iontophoresed onto the forearm of 10 atopic and 10 nonatopic adult subjects. In order to bypass histamine release from mast cells the patients were then challenged directly with histamine by the \"prick\" technique. The size of the resultant wheals was noted. The data obtained allowed the following conclusions: (1) The atopic group responded to histamine with greater wheal size than the nonatopic group. (2) Iontophoresis of diphyenhydramine effectively reduced the magnitude of the histamine wheal in both groups. (3) Isoproterenol decreased the wheal size in both groups. (4) Propranolol increased the wheal size in only the nonatopic group. (5) The successful modulation of the histamine-induced wheal and flare indicated that these drugs, regardless of their effect on the dermal mast cell, exert a measurable effect on the target organ (vasculature)."}
{"id": "PMID:4573", "title": "Further observations on the potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.", "content": "The use of methenamine in the treatment of urinary tract infections due to Proteus species is limited by urine alkalinity. Acetohydroxamic acid, an inhibitor of urease, maintains acidity despite growth of Proteus in urine. Easily achievable concentrations of acetohydroxamic acid in vitro systems that simulated the dynamics of the urinary tract potentiated the antibacterial effect of methenamine against Proteus species. The combined use of a urease inhibitor and methenamine may be effective in the treatment of urinary infection caused by these organisms.", "contents": "Further observations on the potentiation of the antibacterial effect of methenamine by acetohydroxamic acid. The use of methenamine in the treatment of urinary tract infections due to Proteus species is limited by urine alkalinity. Acetohydroxamic acid, an inhibitor of urease, maintains acidity despite growth of Proteus in urine. Easily achievable concentrations of acetohydroxamic acid in vitro systems that simulated the dynamics of the urinary tract potentiated the antibacterial effect of methenamine against Proteus species. The combined use of a urease inhibitor and methenamine may be effective in the treatment of urinary infection caused by these organisms."}
{"id": "PMID:4575", "title": "Hematopoietic thymocyte precursors. I. Assay and kinetics of the appearance of progeny.", "content": "A quantitative assay for the hematopoietic precursor of thymocytes has been developed. Using this assay the kinetics of appearance of the progeny of transfused bone marrow and spleen cells in the thymus of irradiated (760 R) mice has been studied. Precursor cells are seven to eightfold more common in bone marrow than in spleen and are absent from peripheral lymph nodes. They decline in number as the animals age. When hematopoietic cells are injected immediately after lethal irradiation only a small number of cells actually enter the gland. Their progeny are not detectable in the thymus for 8-12 days. The time of their detection depends both upon the size of the residual endogenous thymocyte population and the number of progenitor cells injected. Evidence has been presented that excludes thymic injury as the basis for the delay in the appearance of donor type cells and indicates that neither the production of a \"homing\" signal in the irradiated animal nor the development of precursor cells are limiting factors in the rate of thymic repopulation. These studies indicate that only an exceedingly small number (less than 100) of prothymocytes are required to repopulate the thymus of an irradiated mouse. This restricted number of progenitors must produce the entire repertory of T-cell immunologic responsiveness seen in the first weeks after repopulation.", "contents": "Hematopoietic thymocyte precursors. I. Assay and kinetics of the appearance of progeny. A quantitative assay for the hematopoietic precursor of thymocytes has been developed. Using this assay the kinetics of appearance of the progeny of transfused bone marrow and spleen cells in the thymus of irradiated (760 R) mice has been studied. Precursor cells are seven to eightfold more common in bone marrow than in spleen and are absent from peripheral lymph nodes. They decline in number as the animals age. When hematopoietic cells are injected immediately after lethal irradiation only a small number of cells actually enter the gland. Their progeny are not detectable in the thymus for 8-12 days. The time of their detection depends both upon the size of the residual endogenous thymocyte population and the number of progenitor cells injected. Evidence has been presented that excludes thymic injury as the basis for the delay in the appearance of donor type cells and indicates that neither the production of a \"homing\" signal in the irradiated animal nor the development of precursor cells are limiting factors in the rate of thymic repopulation. These studies indicate that only an exceedingly small number (less than 100) of prothymocytes are required to repopulate the thymus of an irradiated mouse. This restricted number of progenitors must produce the entire repertory of T-cell immunologic responsiveness seen in the first weeks after repopulation."}
{"id": "PMID:4576", "title": "Frog lysozyme. I. Its identification, occurrence as isozymes, and quantitative distribution in tissues of the leopard frog, Rana pipiens.", "content": "In the course of examining the etiology of the Luck\u00e9 renal adenocarcinoma of the frog, Rana pipiens, it was found that organs of the normal adult contain bacteriolytic enzymes. These enzymes all satisfied the six criteria for the identification of lysozymes and at least eight forms were separable by polyacrylamide gel electrophoresis. Their qualitative and quantitative distribution was organ-specific. All eight isozymes were found in normal kidney, while liver and spleen contained seven forms; skin, six; ovarian egg, five; and serum, two. In quantitative assays using a radial diffusion test, spleen had the greatest lysozyme concentration, followed in descending order by kidney, liver, skin, and ovary. Serum contained very low amounts. In terms of enzyme activity per animal, ovary was the highest ranking organ. As such a large number of lysozyme isozymes has not been reported in any other organism, their origins and functions are considered in the context of their presence in an ectotherm.", "contents": "Frog lysozyme. I. Its identification, occurrence as isozymes, and quantitative distribution in tissues of the leopard frog, Rana pipiens. In the course of examining the etiology of the Luck\u00e9 renal adenocarcinoma of the frog, Rana pipiens, it was found that organs of the normal adult contain bacteriolytic enzymes. These enzymes all satisfied the six criteria for the identification of lysozymes and at least eight forms were separable by polyacrylamide gel electrophoresis. Their qualitative and quantitative distribution was organ-specific. All eight isozymes were found in normal kidney, while liver and spleen contained seven forms; skin, six; ovarian egg, five; and serum, two. In quantitative assays using a radial diffusion test, spleen had the greatest lysozyme concentration, followed in descending order by kidney, liver, skin, and ovary. Serum contained very low amounts. In terms of enzyme activity per animal, ovary was the highest ranking organ. As such a large number of lysozyme isozymes has not been reported in any other organism, their origins and functions are considered in the context of their presence in an ectotherm."}
{"id": "PMID:4577", "title": "Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle.", "content": "Na channels of frog skeletal muscle are studied under voltage clamp and their properties compared with those of frog myelinated nerve. A standard mathematical model is fitted to the sodium currents measured in nerve and in muscle to obtain a quantitative description of the gating kinetics. At 5 degrees C the kinetics in frog nerve and skeletal muscle are similar except that activation proceeds five times faster in nerve. Block of Na channels by saxitoxin is measured in nerve and in muscle. The apparent dissociation constants for the inhibitory complex are about 1 nM and not significantly different in nerve and muscle. Block of Na channels by external protons in muscle is found to have an apparent pKalpha of 5.33 and a voltage dependence corresponding to action of 27% of the membrane potential drop. Both values are like those for nerve. Shift of the peak sodium permeability-membrane potential curve with changes of external pH and Ca++ are found to be the same in nerve and muscle. It is concluded that Na channels of nerve and muscle are nearly the same.", "contents": "Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle. Na channels of frog skeletal muscle are studied under voltage clamp and their properties compared with those of frog myelinated nerve. A standard mathematical model is fitted to the sodium currents measured in nerve and in muscle to obtain a quantitative description of the gating kinetics. At 5 degrees C the kinetics in frog nerve and skeletal muscle are similar except that activation proceeds five times faster in nerve. Block of Na channels by saxitoxin is measured in nerve and in muscle. The apparent dissociation constants for the inhibitory complex are about 1 nM and not significantly different in nerve and muscle. Block of Na channels by external protons in muscle is found to have an apparent pKalpha of 5.33 and a voltage dependence corresponding to action of 27% of the membrane potential drop. Both values are like those for nerve. Shift of the peak sodium permeability-membrane potential curve with changes of external pH and Ca++ are found to be the same in nerve and muscle. It is concluded that Na channels of nerve and muscle are nearly the same."}
{"id": "PMID:4578", "title": "Cation transport in Escherichia coli. VIII. Potassium transport mutants.", "content": "Analysis of K transport mutants indicates the existence of four separate K uptake systems in Escherichia coli K-12. A high affinity system called Kdp has a Km of 2 muM, and Vmax at 37 degrees C of 150 mumol/g min. This system is repressed by growth in high concentrations of K. Two constitutive systems, TrkA and TrkD, have Km's of 1.5 and 0.5 mM and Vmax's of 550 and 40 at 37 and 30 degrees C, respectively. Mutants lacking all three of these saturable systems take up K slowly by a process, called TrkF, whose rate of transport is linearly dependent on K concentration up to 105 mM. On the whole, each of these systems appears to function as an independent path for K uptake since the kinetics of uptake when two are present is the sum of each operating alone. This is not true for strains having both the TrkD and Kdp systems, where presence of the latter results in K uptake which saturates at a K concentration well below 0.1 mM. This result indicates some interaction between these systems so that uptake now has the affinity characteristic of the Kdp system. All transport systems are able to extrude Na during K uptake. The measurements of cell Na suggest that growing cells of E. coli have very low concentrations of Na, considerably lower than indicated by earlier studies.", "contents": "Cation transport in Escherichia coli. VIII. Potassium transport mutants. Analysis of K transport mutants indicates the existence of four separate K uptake systems in Escherichia coli K-12. A high affinity system called Kdp has a Km of 2 muM, and Vmax at 37 degrees C of 150 mumol/g min. This system is repressed by growth in high concentrations of K. Two constitutive systems, TrkA and TrkD, have Km's of 1.5 and 0.5 mM and Vmax's of 550 and 40 at 37 and 30 degrees C, respectively. Mutants lacking all three of these saturable systems take up K slowly by a process, called TrkF, whose rate of transport is linearly dependent on K concentration up to 105 mM. On the whole, each of these systems appears to function as an independent path for K uptake since the kinetics of uptake when two are present is the sum of each operating alone. This is not true for strains having both the TrkD and Kdp systems, where presence of the latter results in K uptake which saturates at a K concentration well below 0.1 mM. This result indicates some interaction between these systems so that uptake now has the affinity characteristic of the Kdp system. All transport systems are able to extrude Na during K uptake. The measurements of cell Na suggest that growing cells of E. coli have very low concentrations of Na, considerably lower than indicated by earlier studies."}
{"id": "PMID:4579", "title": "Some properties of the pyruvate carboxylase from Pseudomonas fluorescens.", "content": "The pyruvate carboxylase of Pseudonomas fluorescens was purified 160-fold  from cells grown on glucose at 20 degrees C. The activity of this purified enzyme was not affected by acetyl-coenzyme A or L-aspartate, but was strongly inhibited by ADP, which was competitive towards ATP. Pyruvate gave a broken double reciprocal plot, from which two apparent Km values could be determined, namely 0-08 and 0-21 mM, from the lower and the higher concentration ranges, respectively. The apparent Km for HCO3 at pH 6-9, in the presence of the manganese ATP ion (MnATP2-), was 3-1 mM. The enzyme reaction had an optimum pH value of 7-1 or 9-0 depending on the use of MnATP2- or MgATP2-, respectively, as substrate. Free Mg2+ was an activator at pH values below 9-0. The enzyme was strongly activated by monovalent cations; NH4+ and K+ were the better activators, with apparent Ka values of 0-7 and 1-6 mM, respectively. Partially purified enzymes from cells grown on glucose at 1 or 20 degrees C had the same properties, including the thermal stability. In both cases 50% of the enzyme activity was lost after pre-incubation for 10 min at 46 degrees C. The molecular weight was estimated to be about 300000 daltons by gel filtration on Sephadex G-200. The regulatory properties and molecular weight are thus similar to those determined for the pyruvate carboxylases from Pseudomonas citronellolis and Azotobacter vinelandii.", "contents": "Some properties of the pyruvate carboxylase from Pseudomonas fluorescens. The pyruvate carboxylase of Pseudonomas fluorescens was purified 160-fold  from cells grown on glucose at 20 degrees C. The activity of this purified enzyme was not affected by acetyl-coenzyme A or L-aspartate, but was strongly inhibited by ADP, which was competitive towards ATP. Pyruvate gave a broken double reciprocal plot, from which two apparent Km values could be determined, namely 0-08 and 0-21 mM, from the lower and the higher concentration ranges, respectively. The apparent Km for HCO3 at pH 6-9, in the presence of the manganese ATP ion (MnATP2-), was 3-1 mM. The enzyme reaction had an optimum pH value of 7-1 or 9-0 depending on the use of MnATP2- or MgATP2-, respectively, as substrate. Free Mg2+ was an activator at pH values below 9-0. The enzyme was strongly activated by monovalent cations; NH4+ and K+ were the better activators, with apparent Ka values of 0-7 and 1-6 mM, respectively. Partially purified enzymes from cells grown on glucose at 1 or 20 degrees C had the same properties, including the thermal stability. In both cases 50% of the enzyme activity was lost after pre-incubation for 10 min at 46 degrees C. The molecular weight was estimated to be about 300000 daltons by gel filtration on Sephadex G-200. The regulatory properties and molecular weight are thus similar to those determined for the pyruvate carboxylases from Pseudomonas citronellolis and Azotobacter vinelandii."}
{"id": "PMID:4588", "title": "Cyanide intoxication in the rat: physiological and neuropathological aspects.", "content": "Sodium cyanide was given to rats by intravenous infusion at a rate that would avert apnoea (the first sign of overdosage) in the majority. There was full physiological monitoring in a group under anaesthesia and more limited monitoring in an unanaesthetized group. White matter was damaged in six animals and grey matter additionally in only one. It was concluded that cyanide can damage neurones only through the medium of secondary effects on circulation and respiration.", "contents": "Cyanide intoxication in the rat: physiological and neuropathological aspects. Sodium cyanide was given to rats by intravenous infusion at a rate that would avert apnoea (the first sign of overdosage) in the majority. There was full physiological monitoring in a group under anaesthesia and more limited monitoring in an unanaesthetized group. White matter was damaged in six animals and grey matter additionally in only one. It was concluded that cyanide can damage neurones only through the medium of secondary effects on circulation and respiration."}
{"id": "PMID:4595", "title": "Summer sequential graduate programs in nursing.", "content": "In 1970 Texas Woman's University, College of Nursing instituted summer sequential programs in nursing whereby a student could study for a master's degree by attending the University for three summers. A different clinical focus was added each year from 1970 to 1973. Three sequences have been completed, i.e., clinical focuses of psychiatric-mental health nursing, medical-surgical nursing, and maternal-child nursing. Community health nursing is still in progress. Table II is a tabulation of the number and percentage of students who have entered, have withdrawn, are incomplete, or have graduated. Faculty and students think that the program is successful. Enrollment for the first summer of a three-summer sequence beginning the summer of 1974 was twenty-five students in medical-surgical nursing and fifteen students in psychiatric-mental health nursing.", "contents": "Summer sequential graduate programs in nursing. In 1970 Texas Woman's University, College of Nursing instituted summer sequential programs in nursing whereby a student could study for a master's degree by attending the University for three summers. A different clinical focus was added each year from 1970 to 1973. Three sequences have been completed, i.e., clinical focuses of psychiatric-mental health nursing, medical-surgical nursing, and maternal-child nursing. Community health nursing is still in progress. Table II is a tabulation of the number and percentage of students who have entered, have withdrawn, are incomplete, or have graduated. Faculty and students think that the program is successful. Enrollment for the first summer of a three-summer sequence beginning the summer of 1974 was twenty-five students in medical-surgical nursing and fifteen students in psychiatric-mental health nursing."}
{"id": "PMID:4598", "title": "The multiple assignment: an effective alternative for laboratory experiences.", "content": "The purpose of the study was to test out the efficacy of both the Traditional and the Multiple Assignment approaches to the laboratory experiences of students of nursing. The subjects were 22 students enrolled in the first quarter of an Associate Degree Nursing Program and placed in either the multiple or the traditional laboratory assignment. Results showed the students in the peer experience to be superior in overall performance on tests of Nursing Knowledge, Concept Usage and Self-Esteem. It was concluded that the Multiple Assignment approach to laboratory experiences is a viable and useful method for the education of student nurses.", "contents": "The multiple assignment: an effective alternative for laboratory experiences. The purpose of the study was to test out the efficacy of both the Traditional and the Multiple Assignment approaches to the laboratory experiences of students of nursing. The subjects were 22 students enrolled in the first quarter of an Associate Degree Nursing Program and placed in either the multiple or the traditional laboratory assignment. Results showed the students in the peer experience to be superior in overall performance on tests of Nursing Knowledge, Concept Usage and Self-Esteem. It was concluded that the Multiple Assignment approach to laboratory experiences is a viable and useful method for the education of student nurses."}
{"id": "PMID:4599", "title": "Stability of some pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats.", "content": "The effects of lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme.", "contents": "Stability of some pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. The effects of lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme."}
{"id": "PMID:4601", "title": "Adsorption sites of kaolin.", "content": "The electrophoretic mobility and adsorptive properties of kaolin and kaolin pretreated with anionic and cationic materials were examined over a range of pH values. Pretreatment with anionic compounds had little effect on mobility, while adsorption of cationic species markedly reduced mobility. These results are explained by reference to the structure of kaolin, and the interdependence of adsorption properties and electrophoretic mobility are discussed.", "contents": "Adsorption sites of kaolin. The electrophoretic mobility and adsorptive properties of kaolin and kaolin pretreated with anionic and cationic materials were examined over a range of pH values. Pretreatment with anionic compounds had little effect on mobility, while adsorption of cationic species markedly reduced mobility. These results are explained by reference to the structure of kaolin, and the interdependence of adsorption properties and electrophoretic mobility are discussed."}
{"id": "PMID:4602", "title": "Electrode sensitive to sulfa drugs.", "content": "An electrode sensitive to sulfa drugs was constructed by using the iron(II)-bathophenanthroline chelate embedded in a liquid membrane. Rapid and Nernstian responses were exhibited against solutions of sulfamerazine and sulfisomidine ranging between 10(-3) and 10(-1) M in concentration. High selectivity was observed in the presence of urea, glycine, aminopyrine, or p-amino-benzoic acid. These chemicals are known to interfere in the usual colorimetric analysis of sulfa drugs.", "contents": "Electrode sensitive to sulfa drugs. An electrode sensitive to sulfa drugs was constructed by using the iron(II)-bathophenanthroline chelate embedded in a liquid membrane. Rapid and Nernstian responses were exhibited against solutions of sulfamerazine and sulfisomidine ranging between 10(-3) and 10(-1) M in concentration. High selectivity was observed in the presence of urea, glycine, aminopyrine, or p-amino-benzoic acid. These chemicals are known to interfere in the usual colorimetric analysis of sulfa drugs."}
{"id": "PMID:4603", "title": "Liquid-solid chromatographic determination of 6-demethylgriseofulvin in urine.", "content": "A specific and quantitative liquid-solid chromatographic method for the determination of 6-demethylgriseofulvin in human urine is reported. The method consists of extraction into an organic solvent, addition of internal standard, and analysis by liquid-solid chromatography using a UV detector. Griseofulvin, if present, can be determined simultaneously. The sensitivity of the method is 6 mug/ml of urine. Total 6-demethylgrisefulvin is determined after hydrolysis of the glucuronide conjugate with glucuronidase-sulfatase enzyme solution. The method is well suited for the analysis of a large number of samples.", "contents": "Liquid-solid chromatographic determination of 6-demethylgriseofulvin in urine. A specific and quantitative liquid-solid chromatographic method for the determination of 6-demethylgriseofulvin in human urine is reported. The method consists of extraction into an organic solvent, addition of internal standard, and analysis by liquid-solid chromatography using a UV detector. Griseofulvin, if present, can be determined simultaneously. The sensitivity of the method is 6 mug/ml of urine. Total 6-demethylgrisefulvin is determined after hydrolysis of the glucuronide conjugate with glucuronidase-sulfatase enzyme solution. The method is well suited for the analysis of a large number of samples."}
{"id": "PMID:4605", "title": "Mass fragmentography of morphine: relationship between brain levels and analgesic activity.", "content": "Morphine levels in rat brain were measured by the multiple ion detection method (mass fragmentography), using a computer-controlled gas chromatograph-mass spectrometer, and were correlated with the analgesic activity of the narcotic at intervals up to 6 hours after the injection. Morphine levels in brain reached a peak of 346 ng/g of tissue wet weight 30 minutes after the subcutaneous injection of 10 mg/kg of morphine sulfate and then declined rapidly over the next 3 hours. Between 3 and 6 hours after the injection of morphine, the brain concentration decreased slightly but was still readily detectable at 6 hours after injection. An excellent correlation (r = 0.923) was found between the concentration of morphine in brain and analgesic activity, as measured by the hot plate method. The multiple ion detection method for the measurement of morphine appears to meet all of the criteria necessary for any drug assay: sensitivity, specificity and ease of analysis.", "contents": "Mass fragmentography of morphine: relationship between brain levels and analgesic activity. Morphine levels in rat brain were measured by the multiple ion detection method (mass fragmentography), using a computer-controlled gas chromatograph-mass spectrometer, and were correlated with the analgesic activity of the narcotic at intervals up to 6 hours after the injection. Morphine levels in brain reached a peak of 346 ng/g of tissue wet weight 30 minutes after the subcutaneous injection of 10 mg/kg of morphine sulfate and then declined rapidly over the next 3 hours. Between 3 and 6 hours after the injection of morphine, the brain concentration decreased slightly but was still readily detectable at 6 hours after injection. An excellent correlation (r = 0.923) was found between the concentration of morphine in brain and analgesic activity, as measured by the hot plate method. The multiple ion detection method for the measurement of morphine appears to meet all of the criteria necessary for any drug assay: sensitivity, specificity and ease of analysis."}
{"id": "PMID:4606", "title": "Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat.", "content": "Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals.", "contents": "Vasoconstrictor actions of delta8- and delta9-tetrahydrocannabinol in the rat. Cardiovascular effects of delta8- and delta9-tetrahydrocannabinol (THC) were studied after systemic intravenous administration and intra-arterial administration into a perfused vascular bed in the urethane-anesthetized rat. Intravenous administration of delta8- and delta9-THC produced dose-related transient increases in blood pressure followed by more prolonged hypotensive responses and bradycardia. Intra-arterial administration of delta8- and delta9-THC into the perfused hindquarters of the rat produced an increase in perfusion pressure indicative of vasoconstriction. The vasoconstrictor response to the cannabinoids corresponded temporally to a similar response produced by i.a. norepinephrine and was in contrast to the more prolonged vasoconstrictor responses produced by vasopressin. Phentolamine, in a dose which reduced the vasoconstrictor effect of norepinephrine by 90%, significantly reduced the response to i.a. delta9-THC while having no effect on the actions of i.a. vasopressin. It was demonstrated that reserpine pretreatment significantly reduced vasoconstrictor actions of i.a. tyramine and delta9-THC but did not alter the responses to norepinephrine. These data suggest that delta8- and delta9-THC have peripheral vasoconstrictor activity in the rat which may be mediated, in part, through a tyramine-like action on adrenergic nerve terminals."}
{"id": "PMID:4607", "title": "Possible involvement of a transmitter different from norepinephrine in the residual responses to nerve stimulation of the cat nictitating membrane after pretreatment with reserpine.", "content": "Pretreatment with reserpine (0.3 or 3 mg/kg, 24 hours before the experiment) reduced the norepinephrine (NE) levels in the medial muscle of the cat nictitating membrane to approximately 2% of the control values. Under these experimental conditions, the responses to postganglionic nerve stimulation were not abolished, reaching up to 50% of the maximum development of tension to exogenous sympathomimetic amines both in vivo and in vitro. In contrast to the responses to nerve stimulation obtained in normal nictitating membranes, the residual responses to nerve stimulation obtained after pretreatment with reserpine were not blocked by phentolamine (3.1 and 31 muM) or by 0.29 muM phenoxybenzamine. The effectiveness of phentolamine and phenoxybenzamine in blocking responses to exogenous NE was the same when the normal nictitating membrane was compared to the smooth muscle obtained from cats pretreated with reserpine. The residual responses to nerve stimulation were reduced when the calcium concentration in the medium was decreased to 0.65 mM. These residual responses were abolished in the presence of tetrodotoxin. Scopolamine, 0.078 muM, did not reduce the residual responses to nerve stimulation while it antagonized the responses to exogenous acetylcholine, indicating that a cholinergic mechanism is not involved in this phenomenon. Adenosine triphosphate (ATP) and adenosine diphosphosphate (ADP) behaved as agonists on the smooth muscle of the normal and of the reserpine-pretreated nictitating membrane and the responses to ATP were not blocked by phentolamine. It is concluded that the residual responses to nerve stimulation obtained after pretreatment with reserpine could be due to the release of a transmitter different from NE. The possibility that ATP or ADP might be involved in these residual responses to nerve stimulation is discussed.", "contents": "Possible involvement of a transmitter different from norepinephrine in the residual responses to nerve stimulation of the cat nictitating membrane after pretreatment with reserpine. Pretreatment with reserpine (0.3 or 3 mg/kg, 24 hours before the experiment) reduced the norepinephrine (NE) levels in the medial muscle of the cat nictitating membrane to approximately 2% of the control values. Under these experimental conditions, the responses to postganglionic nerve stimulation were not abolished, reaching up to 50% of the maximum development of tension to exogenous sympathomimetic amines both in vivo and in vitro. In contrast to the responses to nerve stimulation obtained in normal nictitating membranes, the residual responses to nerve stimulation obtained after pretreatment with reserpine were not blocked by phentolamine (3.1 and 31 muM) or by 0.29 muM phenoxybenzamine. The effectiveness of phentolamine and phenoxybenzamine in blocking responses to exogenous NE was the same when the normal nictitating membrane was compared to the smooth muscle obtained from cats pretreated with reserpine. The residual responses to nerve stimulation were reduced when the calcium concentration in the medium was decreased to 0.65 mM. These residual responses were abolished in the presence of tetrodotoxin. Scopolamine, 0.078 muM, did not reduce the residual responses to nerve stimulation while it antagonized the responses to exogenous acetylcholine, indicating that a cholinergic mechanism is not involved in this phenomenon. Adenosine triphosphate (ATP) and adenosine diphosphosphate (ADP) behaved as agonists on the smooth muscle of the normal and of the reserpine-pretreated nictitating membrane and the responses to ATP were not blocked by phentolamine. It is concluded that the residual responses to nerve stimulation obtained after pretreatment with reserpine could be due to the release of a transmitter different from NE. The possibility that ATP or ADP might be involved in these residual responses to nerve stimulation is discussed."}
{"id": "PMID:4608", "title": "Pineal beta adrenergic receptor: correlation of binding of 3H-l-alprenolol with stimulation of adenylate cyclase.", "content": "3H-l-Alprenolol, a potent competitive beta adrenergic antagonist, binds to sites in rat pineal gland membranes. The properties of these binding sites were compared to those of the receptors which mediate the beta adrenergic activation of pineal adenylate cyclase. Both sites are highly stereospecific. The l-stereoisomers of alprenolol and propranolol were at least two orders of magnitude more potent than the d-stereoisomers in inhibiting isoproterenol-stimulated adenylate cyclase or 3H-l-alprenolol binding. The dissociation constants (Kd) of the l-stereoisomers of both alprenolol and propranolol were 10 to 22 nM as determined by competition for binding sites or by inhibition of isoproternol-stimulated adenylate cyclase. Beta adrenergic agonists which stimulated adenylate cyclase also competitively inhibited the binding of 3H-l-alprenolol. They showed the same order of potency (isoproterenol greater than norepinephrine greater than or equal to epinephrine) and the same individual affinities in the two systems. Alpha adrenergic blockers were ineffective in inhibiting either adenylate cyclase stimulation or 3H-l-alprenolol binding. Isoproternol stimulation of adenylate cyclase acrivity, and 3H-l-alprenolol binding, were rapid and rapidly reversible. The 3H-l-alprenolol binding sites were saturable and bound 0.6 pmol of ligand per mg of added protein. The data suggest that the binding of 3H-l-alprenolol occurs at sites indistinguishable from the pineal beta adrenergic receptor.", "contents": "Pineal beta adrenergic receptor: correlation of binding of 3H-l-alprenolol with stimulation of adenylate cyclase. 3H-l-Alprenolol, a potent competitive beta adrenergic antagonist, binds to sites in rat pineal gland membranes. The properties of these binding sites were compared to those of the receptors which mediate the beta adrenergic activation of pineal adenylate cyclase. Both sites are highly stereospecific. The l-stereoisomers of alprenolol and propranolol were at least two orders of magnitude more potent than the d-stereoisomers in inhibiting isoproterenol-stimulated adenylate cyclase or 3H-l-alprenolol binding. The dissociation constants (Kd) of the l-stereoisomers of both alprenolol and propranolol were 10 to 22 nM as determined by competition for binding sites or by inhibition of isoproternol-stimulated adenylate cyclase. Beta adrenergic agonists which stimulated adenylate cyclase also competitively inhibited the binding of 3H-l-alprenolol. They showed the same order of potency (isoproterenol greater than norepinephrine greater than or equal to epinephrine) and the same individual affinities in the two systems. Alpha adrenergic blockers were ineffective in inhibiting either adenylate cyclase stimulation or 3H-l-alprenolol binding. Isoproternol stimulation of adenylate cyclase acrivity, and 3H-l-alprenolol binding, were rapid and rapidly reversible. The 3H-l-alprenolol binding sites were saturable and bound 0.6 pmol of ligand per mg of added protein. The data suggest that the binding of 3H-l-alprenolol occurs at sites indistinguishable from the pineal beta adrenergic receptor."}
{"id": "PMID:4609", "title": "A pharmacological analysis of neurally induced inhibition of carotid body chemoreceptor activity in cats.", "content": "Experiments were performed to determine the mechanism by which centrifugal impulses in the carotid sinus nerve (CSN) reduce the frequency of impulse traffic in afferent chemoreceptor fibers from the carotid body in cats. Recordings of chemoreceptor activity were made from single- or few-fiber preparations dissected off the CSN, while the remainder of the CSN was stimulated electrically to produce neurally induced inhibition of chemoreceptor activity. Various drugs were injected either intravenously or directly into the arterial blood supply to the carotid body. We found that catecholamines (dopamine, norepinephrine and epinephrine) inhibited spontaneous chemoreceptor activity, and that alpha adrenergic antagonists abolished both this inhibition and that produced by electrical stimulation of the CSN in the same preparation. Atropine, but not nicotinic antagonists of acetylcholine, consistently blocked neurally induced inhibition but not that produced by catecholamines. Muscarinic agonists had no effect on spontaneous chemoreceptor activity. We conclude that centrifugal activity in the CSN causes release of endogenous catecholamines in the carotid body, and that these catecholamines mediate neurally induced inhibition of chemoreceptor activity is due to the vasomotor effects of acetylcholine.", "contents": "A pharmacological analysis of neurally induced inhibition of carotid body chemoreceptor activity in cats. Experiments were performed to determine the mechanism by which centrifugal impulses in the carotid sinus nerve (CSN) reduce the frequency of impulse traffic in afferent chemoreceptor fibers from the carotid body in cats. Recordings of chemoreceptor activity were made from single- or few-fiber preparations dissected off the CSN, while the remainder of the CSN was stimulated electrically to produce neurally induced inhibition of chemoreceptor activity. Various drugs were injected either intravenously or directly into the arterial blood supply to the carotid body. We found that catecholamines (dopamine, norepinephrine and epinephrine) inhibited spontaneous chemoreceptor activity, and that alpha adrenergic antagonists abolished both this inhibition and that produced by electrical stimulation of the CSN in the same preparation. Atropine, but not nicotinic antagonists of acetylcholine, consistently blocked neurally induced inhibition but not that produced by catecholamines. Muscarinic agonists had no effect on spontaneous chemoreceptor activity. We conclude that centrifugal activity in the CSN causes release of endogenous catecholamines in the carotid body, and that these catecholamines mediate neurally induced inhibition of chemoreceptor activity is due to the vasomotor effects of acetylcholine."}
{"id": "PMID:4610", "title": "On the ability of narcotic antagonists to produce the narcotic cue.", "content": "The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability.", "contents": "On the ability of narcotic antagonists to produce the narcotic cue. The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability."}
{"id": "PMID:4611", "title": "Effect of para-aminohippurate on renal glutamine metabolism in the rat.", "content": "After para-aminohippurate (PAH) infusion into rats, urine pH decreased and urine ammonium excretion increased. Because augmented urine flow and decreased urine pH could not explain entirely the enhanced ammonium excretion, an increased ammonia production was postulated as a contributing influence. This was supported by the in vitro findings that PAH could increase slice ammoniagenesis from glutamine. The ability of PAH to stimulate ammoniagenesis in vitro was attributed to enhanced phosphate-dependent glutaminase activity. We conclude that PAH infusions at certain concentrations in vivo can alter ammonium excretion through increased renal ammonia production. The latter may be secondary to enhanced phosphate-dependent glutaminase activity.", "contents": "Effect of para-aminohippurate on renal glutamine metabolism in the rat. After para-aminohippurate (PAH) infusion into rats, urine pH decreased and urine ammonium excretion increased. Because augmented urine flow and decreased urine pH could not explain entirely the enhanced ammonium excretion, an increased ammonia production was postulated as a contributing influence. This was supported by the in vitro findings that PAH could increase slice ammoniagenesis from glutamine. The ability of PAH to stimulate ammoniagenesis in vitro was attributed to enhanced phosphate-dependent glutaminase activity. We conclude that PAH infusions at certain concentrations in vivo can alter ammonium excretion through increased renal ammonia production. The latter may be secondary to enhanced phosphate-dependent glutaminase activity."}
{"id": "PMID:4612", "title": "Inhibition by sulfobromophthalein of mitochondrial translocation of anions and adenine nucleotides: effects upon liver adenosine triphosphate and possible correlation with inhibition of bile flow in the rat.", "content": "Unconjugated sulfobromophthalein (BSP) inhibits state III respiration of rat liver mitochondria. It competitively inhibits the translocation into mitochondria of citrate, malate, phosphate and adenosine diphosphate, as studied by the inhibitor stop method. A double-beam spectrophotometric study strongly suggests that glutamate translocation is similarly inhibited. After perfusion of 65 mumol/hr/100 g for 90 minutes, bile flow is inhibited by 82% and liver adenosine triphosphate (ATP) falls by 60%. The amount of mitochondrial BSP can be computed form the amount of [35S] BSP still bound to mitochondria that are prepared at the end of such experiments; the amount of BSP lost during the isolation procedure is estimated from parallel experiments following binding of BSP in vitro. Comparison of the kinetic constants of mitochondrial transport and of their inhibition by BSP on the one hand and of liver concentration of substrates and BSP on the other gives rise to the conclusion that a strong inhibition of transports, mainly of phosphate, occurs in vivo and is responsible for the concomitant decrease in bile flow.", "contents": "Inhibition by sulfobromophthalein of mitochondrial translocation of anions and adenine nucleotides: effects upon liver adenosine triphosphate and possible correlation with inhibition of bile flow in the rat. Unconjugated sulfobromophthalein (BSP) inhibits state III respiration of rat liver mitochondria. It competitively inhibits the translocation into mitochondria of citrate, malate, phosphate and adenosine diphosphate, as studied by the inhibitor stop method. A double-beam spectrophotometric study strongly suggests that glutamate translocation is similarly inhibited. After perfusion of 65 mumol/hr/100 g for 90 minutes, bile flow is inhibited by 82% and liver adenosine triphosphate (ATP) falls by 60%. The amount of mitochondrial BSP can be computed form the amount of [35S] BSP still bound to mitochondria that are prepared at the end of such experiments; the amount of BSP lost during the isolation procedure is estimated from parallel experiments following binding of BSP in vitro. Comparison of the kinetic constants of mitochondrial transport and of their inhibition by BSP on the one hand and of liver concentration of substrates and BSP on the other gives rise to the conclusion that a strong inhibition of transports, mainly of phosphate, occurs in vivo and is responsible for the concomitant decrease in bile flow."}
{"id": "PMID:4613", "title": "Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta.", "content": "The dissociation constants (KA values) of l-norepinephrine (l-NE) and seven other agonists acting on alpha adrenergic receptors in rabbit aorta strips were determined by analysis of concentration-response data before and after fractional inactivation of receptors with Dibenamine. In experiments to determine KA values, propranolol was added to block activation of beta receptors and cocaine to block the neuronal uptake mechanism. The KA of l-NE and the KA of a second agonist, when determined on paired strips from the same aorta, were used to calculate the relative affinity and the relative efficacy (er) of the second agonist as compared to l-NE. The validity of the method used for determining KA and er values was supported by the following findings. 1) The dissociation constant (KB) of the competitive antagonist, phentolamine, determined with each of the agonists, was the same as that determined with l-NE. 2) The KA determined for l-NE was independent of the fraction of active receptors remaining (q) after pretreatment with different concentrations of Dibenamine. 3) The KB of phentolamine determined with l-NE as the agonist was the same before and after fractional inactivation of receptors. 4) After inactivation in paired strips by equal exposures to Dibenamine, the q value determined with each agonist was the same as that determined with l-NE. The mean KA value for l-NE was 3.39 +/- 0.15 X 10(-7) M. The mean relative affinities of the agonists for the alpha receptor were: l-NE, 1;L-EPINEPHRINE, 1.25; L-PHENYLEPHRINE, 0.200; L-norphenylephrine, 0.217; epinine, 0.136; dopamine, 0.0055; l-alpha-methylnorepinephrine, 0.095; dl-alpha-ethylnorepinephrine, 0.0048. The mean er of each agonist was not significantly different from that of l-NE, except for l-norphenylephrine with an e of 0.71, and dl-alpha-ethylnorepinephrine with an er of 0.41. The results are discussed from the standpoint of structure-activity relationships.", "contents": "Dissociation constants and relative efficacies of agonists acting on alpha adrenergic receptors in rabbit aorta. The dissociation constants (KA values) of l-norepinephrine (l-NE) and seven other agonists acting on alpha adrenergic receptors in rabbit aorta strips were determined by analysis of concentration-response data before and after fractional inactivation of receptors with Dibenamine. In experiments to determine KA values, propranolol was added to block activation of beta receptors and cocaine to block the neuronal uptake mechanism. The KA of l-NE and the KA of a second agonist, when determined on paired strips from the same aorta, were used to calculate the relative affinity and the relative efficacy (er) of the second agonist as compared to l-NE. The validity of the method used for determining KA and er values was supported by the following findings. 1) The dissociation constant (KB) of the competitive antagonist, phentolamine, determined with each of the agonists, was the same as that determined with l-NE. 2) The KA determined for l-NE was independent of the fraction of active receptors remaining (q) after pretreatment with different concentrations of Dibenamine. 3) The KB of phentolamine determined with l-NE as the agonist was the same before and after fractional inactivation of receptors. 4) After inactivation in paired strips by equal exposures to Dibenamine, the q value determined with each agonist was the same as that determined with l-NE. The mean KA value for l-NE was 3.39 +/- 0.15 X 10(-7) M. The mean relative affinities of the agonists for the alpha receptor were: l-NE, 1;L-EPINEPHRINE, 1.25; L-PHENYLEPHRINE, 0.200; L-norphenylephrine, 0.217; epinine, 0.136; dopamine, 0.0055; l-alpha-methylnorepinephrine, 0.095; dl-alpha-ethylnorepinephrine, 0.0048. The mean er of each agonist was not significantly different from that of l-NE, except for l-norphenylephrine with an e of 0.71, and dl-alpha-ethylnorepinephrine with an er of 0.41. The results are discussed from the standpoint of structure-activity relationships."}
{"id": "PMID:4614", "title": "The effect of carbon dioxide on the intracellular pH and buffering power of snail neurones.", "content": "1. Intracellular pH (pHi) was measured using pH-sensitive glass micro-electrodes. The effects on pHi of CO2 applied externally and HCO3-, H+ and NH4+ injected iontophoretically, were investigated. 2. The transport numbers for iontophoretic injection into aqueous micro-droples were found by potentiometric titration to be 0-3 for HCO3- and 0-94 for H+. 3. Exposure to Ringer, pH 7-5, equilibrated with 2-2% CO2 caused a rapid, but only transient, fall in pHi. Within 1 or 2 min pHi began to return exponentially to normal, with a time constant of about 5 min. 4. When external CO2 was removed, pHi rapidly increased, and then slowly returned to normal. The pHi changes with CO2 application or removal gave a calculated intracellular buffer value of about 30 m-equiv H+/pH unit per litre. 5. Injection of HCO3- caused a rise in pHi very similar to that seen on removal of external CO2. 6. The pHi responses to CO2 application, CO2 removal and HCO3- injection were slowed by the carbonic anhydrase inhibitor acetazolamide. 7. H+ injection caused a transient fall in pHi. In CO2 Ringer pHi fell less and recovered faster than in CO2-free Ringer. Calculation of the internal buffer value from the pHi responses to H+ and HCO3- injection gave very similar values. 8. The internal buffer value (measured by H+ injection) was greatly increased by exposure to CO2 Ringer. Acetazolamide reduced this effect of CO2, suggesting that the function of intracellular carbonic anhydrase may be to maximize the internal buffering power in CO2. 9. It was concluded that the internal HCO3- was determined primarily by the CO2 level and pHi, that internal HCO3- made a large contribution to the buffering power, and that after internal acidfication pHi was restored to normal by active transport of H+, OH- or HCO3- across the cell membrane. The active transport was much faster in CO2 than in CO2-free Ringer.", "contents": "The effect of carbon dioxide on the intracellular pH and buffering power of snail neurones. 1. Intracellular pH (pHi) was measured using pH-sensitive glass micro-electrodes. The effects on pHi of CO2 applied externally and HCO3-, H+ and NH4+ injected iontophoretically, were investigated. 2. The transport numbers for iontophoretic injection into aqueous micro-droples were found by potentiometric titration to be 0-3 for HCO3- and 0-94 for H+. 3. Exposure to Ringer, pH 7-5, equilibrated with 2-2% CO2 caused a rapid, but only transient, fall in pHi. Within 1 or 2 min pHi began to return exponentially to normal, with a time constant of about 5 min. 4. When external CO2 was removed, pHi rapidly increased, and then slowly returned to normal. The pHi changes with CO2 application or removal gave a calculated intracellular buffer value of about 30 m-equiv H+/pH unit per litre. 5. Injection of HCO3- caused a rise in pHi very similar to that seen on removal of external CO2. 6. The pHi responses to CO2 application, CO2 removal and HCO3- injection were slowed by the carbonic anhydrase inhibitor acetazolamide. 7. H+ injection caused a transient fall in pHi. In CO2 Ringer pHi fell less and recovered faster than in CO2-free Ringer. Calculation of the internal buffer value from the pHi responses to H+ and HCO3- injection gave very similar values. 8. The internal buffer value (measured by H+ injection) was greatly increased by exposure to CO2 Ringer. Acetazolamide reduced this effect of CO2, suggesting that the function of intracellular carbonic anhydrase may be to maximize the internal buffering power in CO2. 9. It was concluded that the internal HCO3- was determined primarily by the CO2 level and pHi, that internal HCO3- made a large contribution to the buffering power, and that after internal acidfication pHi was restored to normal by active transport of H+, OH- or HCO3- across the cell membrane. The active transport was much faster in CO2 than in CO2-free Ringer."}
{"id": "PMID:4615", "title": "[Blood acid-base changes produced by variations of water oxygenation in the crab Carcinus maenas (author's transl)].", "content": "10 Blood acid-base changes were studied at 17 degrees C in immersed crabs (Carcinus maenas) exposed to hypoxic and hyperoxic conditions, by measuring the pH and the CO2 partial pressure, PbCO2, and by calculating the bicarbonate concentration. 20 Hyperoxia first induces a marked respiratory acidosis with a rise of PbCO2. This acidosis is compensated thereafter by a non-ventilatory increase of the blood buffer base concentration. These results are discussed in relation to the general problems concerning the control of the blood acid-base balance in aquatic animals.", "contents": "[Blood acid-base changes produced by variations of water oxygenation in the crab Carcinus maenas (author's transl)]. 10 Blood acid-base changes were studied at 17 degrees C in immersed crabs (Carcinus maenas) exposed to hypoxic and hyperoxic conditions, by measuring the pH and the CO2 partial pressure, PbCO2, and by calculating the bicarbonate concentration. 20 Hyperoxia first induces a marked respiratory acidosis with a rise of PbCO2. This acidosis is compensated thereafter by a non-ventilatory increase of the blood buffer base concentration. These results are discussed in relation to the general problems concerning the control of the blood acid-base balance in aquatic animals."}
{"id": "PMID:4617", "title": "The diagnosis and treatment of acid-base deranged dogs infected with Babesia canis.", "content": "A study was made of the acid-base status of Babesia canis infected dogs judged unlikely to recover after specific babesicidal drug therapy despite the use of blood transfusion and other conventional supportive measures. Such cases were invariably acidotic and responded well and often dramatically to supportive intravenous sodium bicarbonate administration. Elevated blood urea nitrogen, also responded gratifyingly to this procedure. The rationale is discussed in some detail.", "contents": "The diagnosis and treatment of acid-base deranged dogs infected with Babesia canis. A study was made of the acid-base status of Babesia canis infected dogs judged unlikely to recover after specific babesicidal drug therapy despite the use of blood transfusion and other conventional supportive measures. Such cases were invariably acidotic and responded well and often dramatically to supportive intravenous sodium bicarbonate administration. Elevated blood urea nitrogen, also responded gratifyingly to this procedure. The rationale is discussed in some detail."}
{"id": "PMID:4624", "title": "Regulation of cell volume and ion concentrations in a Halobacterium.", "content": "Changes in cell volume and ion content of a Halobacterium species are described in terms of the NaCl concentration (0.5--3.5M) and pH(4-8) of the suspending medium. Cell volume, per unit content of protein of bacteria in stationary phase cultures, rose as the [NaCl] of the growth medium was increased. Logarithmic-phase bacteria shrank as the pH fell from 7 to 5.5. These changes are characteristic of bacteria with a moderate or rapid rate of O2 consumption. Starving (i.e. nonmetabolizing) bacteria, on the other hand, did not change in size within the above ranges of [NaCl] and pH. At lower values, however, such bacteria swelled and eventually lysed. Effects of low pH on cell ions are compared in metabolizing and starving bacteria, and it is shown that changes in the state of the cell K are correlated with movements of cell Na. It appears that the cell K is used to maintain cell [Na] below the NaCl concentration of the medium. The results are explained in terms of a model involving interactions between polyelectrolytes, salts and water in the concentrated cytoplasm of these halophilic organisms.", "contents": "Regulation of cell volume and ion concentrations in a Halobacterium. Changes in cell volume and ion content of a Halobacterium species are described in terms of the NaCl concentration (0.5--3.5M) and pH(4-8) of the suspending medium. Cell volume, per unit content of protein of bacteria in stationary phase cultures, rose as the [NaCl] of the growth medium was increased. Logarithmic-phase bacteria shrank as the pH fell from 7 to 5.5. These changes are characteristic of bacteria with a moderate or rapid rate of O2 consumption. Starving (i.e. nonmetabolizing) bacteria, on the other hand, did not change in size within the above ranges of [NaCl] and pH. At lower values, however, such bacteria swelled and eventually lysed. Effects of low pH on cell ions are compared in metabolizing and starving bacteria, and it is shown that changes in the state of the cell K are correlated with movements of cell Na. It appears that the cell K is used to maintain cell [Na] below the NaCl concentration of the medium. The results are explained in terms of a model involving interactions between polyelectrolytes, salts and water in the concentrated cytoplasm of these halophilic organisms."}
{"id": "PMID:4627", "title": "Behavioral and psychodynamic dimensions of the new sex therapy.", "content": "The new sexual therapy, a brief outpatient treatment of sexual dysfunction consisting of structured sexual exercises and conjoint therapeutic sessions, is a systematic intergration of behavioral and psychodynamic elements. Formally consisting of many defining characteristics of a behavior therapy including the direct treatment of a specified problem and the application of behavioral principles, the new sex therapy also relies on psychodynamic understanding. The result is synergistic. Psychodynamic understanding underlies appropriate behavioral intervention, and psychodynamic exploration of resistance enhances the effectiveness of behavioral methods. Behavioral techniques facilitate the most rapid implementation of therapeutic insight. The integration of approaches in the new sex therapy has general significance for psychotherapeutic theory and practice.", "contents": "Behavioral and psychodynamic dimensions of the new sex therapy. The new sexual therapy, a brief outpatient treatment of sexual dysfunction consisting of structured sexual exercises and conjoint therapeutic sessions, is a systematic intergration of behavioral and psychodynamic elements. Formally consisting of many defining characteristics of a behavior therapy including the direct treatment of a specified problem and the application of behavioral principles, the new sex therapy also relies on psychodynamic understanding. The result is synergistic. Psychodynamic understanding underlies appropriate behavioral intervention, and psychodynamic exploration of resistance enhances the effectiveness of behavioral methods. Behavioral techniques facilitate the most rapid implementation of therapeutic insight. The integration of approaches in the new sex therapy has general significance for psychotherapeutic theory and practice."}
{"id": "PMID:4628", "title": "The use of microchemical techniques for the identification of new transmitter molecules in neurons.", "content": "The author reviews available microtechniques and results on cellular analysis of single neurons emphasizing the identification of putative neurotransmitter molecules. Highly sensitive microquantitative methods for identification and assay of known and putative neurotransmitters have been developed within the last 15 years. Several of the methods reported in the article fulfill the requirements of both specificity and sensitivity for exploring and measuring the level of transmitter molecules in single neurons. Some of the available techniques, mostly those which associate GC or TLC with MS, have been able to unambiguously demonstrate the presence of putative neurotransmitter molecules, or at least of substances which are strongly suspected of fulfilling a functional role in the nervous system.", "contents": "The use of microchemical techniques for the identification of new transmitter molecules in neurons. The author reviews available microtechniques and results on cellular analysis of single neurons emphasizing the identification of putative neurotransmitter molecules. Highly sensitive microquantitative methods for identification and assay of known and putative neurotransmitters have been developed within the last 15 years. Several of the methods reported in the article fulfill the requirements of both specificity and sensitivity for exploring and measuring the level of transmitter molecules in single neurons. Some of the available techniques, mostly those which associate GC or TLC with MS, have been able to unambiguously demonstrate the presence of putative neurotransmitter molecules, or at least of substances which are strongly suspected of fulfilling a functional role in the nervous system."}
{"id": "PMID:4631", "title": "Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa.", "content": "Normal vaginal fluid from premenopausal volunteers was inoculated with 10 strains of Proteus mirabilis and 14 strains of Pseudomonas aeruginosa at pH's of 4.3, 4.6 and 4.9. All bacteria were killed at pH 4.3. Nine of 10 strains of Proteus mirabilis and 12 of 14 Pseudomonas aeruginosa were killed at pH 4.6. Only 4 of 14 strains of Pseudomonas aeruginosa were killed at pH 4.9, while 8 of 10 strains of Proteus mirabilis were killed at the same pH. We conclude that in comparison to the common 0 group strains of Escherichia coli, vaginal fluid is more bactericidal to Proteus mirabilis and Pseudomonas aeruginosa and that these observations may help explain the relative infrequency of bacteriuria owing to the organisms.", "contents": "Studies of introital colonization in women with recurrent urinary infections. V. The inhibitory activity of normal vaginal fluid on Proteus mirabilis and Pseudomonas aeruginosa. Normal vaginal fluid from premenopausal volunteers was inoculated with 10 strains of Proteus mirabilis and 14 strains of Pseudomonas aeruginosa at pH's of 4.3, 4.6 and 4.9. All bacteria were killed at pH 4.3. Nine of 10 strains of Proteus mirabilis and 12 of 14 Pseudomonas aeruginosa were killed at pH 4.6. Only 4 of 14 strains of Pseudomonas aeruginosa were killed at pH 4.9, while 8 of 10 strains of Proteus mirabilis were killed at the same pH. We conclude that in comparison to the common 0 group strains of Escherichia coli, vaginal fluid is more bactericidal to Proteus mirabilis and Pseudomonas aeruginosa and that these observations may help explain the relative infrequency of bacteriuria owing to the organisms."}
{"id": "PMID:4632", "title": "Successful autotransplantation of an intra-abdominal testis to the scrotum by microvascular technique.", "content": "An intra-abdominal testis in a child with prune belly syndrome was successfully transplanted to the scrotum by a microvascular technique. Immediate results were good with no palpable atrophy of the testis. Long-term results (fertility) will not be known for many years. The technique of microvascular anastomosis and its application to orchiopexy are described.", "contents": "Successful autotransplantation of an intra-abdominal testis to the scrotum by microvascular technique. An intra-abdominal testis in a child with prune belly syndrome was successfully transplanted to the scrotum by a microvascular technique. Immediate results were good with no palpable atrophy of the testis. Long-term results (fertility) will not be known for many years. The technique of microvascular anastomosis and its application to orchiopexy are described."}
{"id": "PMID:4633", "title": "Two rare cases of ectopic testis.", "content": "A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy.", "contents": "Two rare cases of ectopic testis. A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy."}
{"id": "PMID:4634", "title": "Familial persistent M\u00fcllerian duct syndrome.", "content": "Two phenotypically normal pre-adolescent brothers with bilateral undescended testes were found to have bilateral fallopian tubes, a uterus and a vagina that drained into the prostatic utricle. We have documented this condition radiographically for the first time, gained some insight into the pattern of inheritance and made recommendations for surgical management.", "contents": "Familial persistent M\u00fcllerian duct syndrome. Two phenotypically normal pre-adolescent brothers with bilateral undescended testes were found to have bilateral fallopian tubes, a uterus and a vagina that drained into the prostatic utricle. We have documented this condition radiographically for the first time, gained some insight into the pattern of inheritance and made recommendations for surgical management."}
{"id": "PMID:4640", "title": "Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (II). Analysis by the uptake saturation model.", "content": "Curves of experimentally plotted log (dose ratio-1) vs.-log [B] for the antagonism between adrenergic beta-mimetics, isoproterenol (ISO) and trimetoquinol (TMQ), and various beta-antagonists in relaxation of guinea-pig trachea could not be reasonably fitted to Schild's equation which has been commonly used in the analysis of drug-antagonism. Taking into consideration the saturable uptake process of the drug used herein, the equation presented in this paper fitted fairly well to the experimental curves and explains the following results: 1, TMQ was more strongly antagonized than ISO by all the blocking agents tested, that is, the apparent modes of antagonism were different between ISO and TMQ although they are considered to interact with the same receptor site. 2, The slope of the curve for a given antagonist markedly differed between ISO and TMQ. It is hypothesized that ISO is more easily taken up than TMQ. This was experimentally confirmed: i.e., ISO was potentiated about 8 fold by inhibiting the uptake process with dibenamine while TMQ was not. By pretreatment with dibenamine, the log (dose ratio-1) vs.-log [B] curve for the ISO-propranolol antagonism was shifted upward and superimposed with the theoretical curve of antagonism in which uptake of the agonist was neglected.", "contents": "Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (II). Analysis by the uptake saturation model. Curves of experimentally plotted log (dose ratio-1) vs.-log [B] for the antagonism between adrenergic beta-mimetics, isoproterenol (ISO) and trimetoquinol (TMQ), and various beta-antagonists in relaxation of guinea-pig trachea could not be reasonably fitted to Schild's equation which has been commonly used in the analysis of drug-antagonism. Taking into consideration the saturable uptake process of the drug used herein, the equation presented in this paper fitted fairly well to the experimental curves and explains the following results: 1, TMQ was more strongly antagonized than ISO by all the blocking agents tested, that is, the apparent modes of antagonism were different between ISO and TMQ although they are considered to interact with the same receptor site. 2, The slope of the curve for a given antagonist markedly differed between ISO and TMQ. It is hypothesized that ISO is more easily taken up than TMQ. This was experimentally confirmed: i.e., ISO was potentiated about 8 fold by inhibiting the uptake process with dibenamine while TMQ was not. By pretreatment with dibenamine, the log (dose ratio-1) vs.-log [B] curve for the ISO-propranolol antagonism was shifted upward and superimposed with the theoretical curve of antagonism in which uptake of the agonist was neglected."}
{"id": "PMID:4645", "title": "pH of sweat of patients with cystic fibrosis.", "content": "pH of the sweat from patients with cystic fibrosis and in controls was measured as a function of the sweat-rate using a fluorescence-pH-indicator (umbelliferone). In both populations sweat is acid at low sweat-rates and alkaline at high ones. The results do not favour an abnormality of the ductal H+-secretion as the pathomechanism of cystic fibrosis.", "contents": "pH of sweat of patients with cystic fibrosis. pH of the sweat from patients with cystic fibrosis and in controls was measured as a function of the sweat-rate using a fluorescence-pH-indicator (umbelliferone). In both populations sweat is acid at low sweat-rates and alkaline at high ones. The results do not favour an abnormality of the ductal H+-secretion as the pathomechanism of cystic fibrosis."}
{"id": "PMID:4649", "title": "Morphologic and biochemical changes in autolysing dog heart muscle.", "content": "The progressive changes in pH, lactate content, and light and electron microscopic appearances were studied in dog myocardium undergoing a 6-hour period of autolysis in vitro at 37 degrees C. and at room temperature. At 37 degrees C. there was a rapid cumulative fall in pH during the 1st hour after excision of the heart and a corresponding increase in lactate content, but little additional change in either subsequently. The nature and sequence of the morphologic alterations at this temperature were generally similar to those which occur in ischemic myocardium in vivo. At room temperature, a much slower cumulative decrease in pH and increase in lactate content took place throughout the whole period of investigation and was paralleled by a slower rate of development of morphologic change.", "contents": "Morphologic and biochemical changes in autolysing dog heart muscle. The progressive changes in pH, lactate content, and light and electron microscopic appearances were studied in dog myocardium undergoing a 6-hour period of autolysis in vitro at 37 degrees C. and at room temperature. At 37 degrees C. there was a rapid cumulative fall in pH during the 1st hour after excision of the heart and a corresponding increase in lactate content, but little additional change in either subsequently. The nature and sequence of the morphologic alterations at this temperature were generally similar to those which occur in ischemic myocardium in vivo. At room temperature, a much slower cumulative decrease in pH and increase in lactate content took place throughout the whole period of investigation and was paralleled by a slower rate of development of morphologic change."}
{"id": "PMID:4648", "title": "[Conditioning of water regenerated from moisture-containing wastes].", "content": "Conditioning of reclaimed water with minerals and trace elements by means of filters made of silver-plated natural minerals containing calcium, magnesium, fluoride and iodine ions has been investigated. On the basis of the investigations a complex filter made of silver plated minerals--dolomite and fluorite--has been developed. This filter allows simultaneous mineralization and decontamination of reclaimed water and preparation of biologically complete potable water.", "contents": "[Conditioning of water regenerated from moisture-containing wastes]. Conditioning of reclaimed water with minerals and trace elements by means of filters made of silver-plated natural minerals containing calcium, magnesium, fluoride and iodine ions has been investigated. On the basis of the investigations a complex filter made of silver plated minerals--dolomite and fluorite--has been developed. This filter allows simultaneous mineralization and decontamination of reclaimed water and preparation of biologically complete potable water."}
{"id": "PMID:4647", "title": "[Problem of \"biological compatibility\" of crew members during prolonged space flight and possible directions for its solution].", "content": "The concept of biological compatibility of men can be defined as a phenomenon which includes an effect (that might be favorable or unfavorable) of one individuum on the other via trace amounts of chemicals released into their environment and micro-organisms. The paper presents the main results of studies of biological compatibility of crewmembers of space vehicles and outlines possible directions of research to be carried out in this area.", "contents": "[Problem of \"biological compatibility\" of crew members during prolonged space flight and possible directions for its solution]. The concept of biological compatibility of men can be defined as a phenomenon which includes an effect (that might be favorable or unfavorable) of one individuum on the other via trace amounts of chemicals released into their environment and micro-organisms. The paper presents the main results of studies of biological compatibility of crewmembers of space vehicles and outlines possible directions of research to be carried out in this area."}
{"id": "PMID:4657", "title": "Proteins of the hepatoma tissue culture cell plasma membrane.", "content": "The specificity of lactoperoxidase-catalyzed iodination for the proteins of the hepatoma tissue culture cell plasma membrane was examined by histochemical, biochemical, and cell fractionation techniques. Light microscope autoradiography of sectioned cells shows the incorporated label to be localized primarily at the periphery of the cell. Most of this label can be released from the cell by trypsin but not by collagenase or hyaluronidase. The label is recovered from the cells as either monoiodotyrosine or diiodotyrosine after hydrolysis of cell extracts with a mixture of proteolytic enzymes. The label co-purifies during cell fractionation with an authentic liver cell plasma membrane marker enzyme, 5'-nucleotidase. Thus, the incorporated iodide is itself a valid marker for those membrane polypeptides having tyrosine residues accessible to the lactoperoxidase. The polypeptide complexity of the purified plasma membrane was examined by high resolution dodecyl sulfate-polyacrylamide gel electrophoresis. At least 50 polypeptides in the membrane are accessible to iodination. These polypeptides probably represent the bulk of the protein mass of the membrane and iodinating them does not affect cell viability, growth rate, or cell function. Labeling experiments with fucose and glucosamine show that at least nine of the iodinated peptides may be glycoproteins.", "contents": "Proteins of the hepatoma tissue culture cell plasma membrane. The specificity of lactoperoxidase-catalyzed iodination for the proteins of the hepatoma tissue culture cell plasma membrane was examined by histochemical, biochemical, and cell fractionation techniques. Light microscope autoradiography of sectioned cells shows the incorporated label to be localized primarily at the periphery of the cell. Most of this label can be released from the cell by trypsin but not by collagenase or hyaluronidase. The label is recovered from the cells as either monoiodotyrosine or diiodotyrosine after hydrolysis of cell extracts with a mixture of proteolytic enzymes. The label co-purifies during cell fractionation with an authentic liver cell plasma membrane marker enzyme, 5'-nucleotidase. Thus, the incorporated iodide is itself a valid marker for those membrane polypeptides having tyrosine residues accessible to the lactoperoxidase. The polypeptide complexity of the purified plasma membrane was examined by high resolution dodecyl sulfate-polyacrylamide gel electrophoresis. At least 50 polypeptides in the membrane are accessible to iodination. These polypeptides probably represent the bulk of the protein mass of the membrane and iodinating them does not affect cell viability, growth rate, or cell function. Labeling experiments with fucose and glucosamine show that at least nine of the iodinated peptides may be glycoproteins."}
{"id": "PMID:4658", "title": "Lesion-induced synaptogenesis in brain: a study of dynamic changes in neuronal membrane specializations.", "content": "When incoming fibers to a given brain region are damaged and degenerate, the remaining undamaged fibers can, in some cases, form new synapses, and restore physiologically functional circuitry. Synaptic membrane events underlie this reconstruction: the connection between membranes is broken and reformed.", "contents": "Lesion-induced synaptogenesis in brain: a study of dynamic changes in neuronal membrane specializations. When incoming fibers to a given brain region are damaged and degenerate, the remaining undamaged fibers can, in some cases, form new synapses, and restore physiologically functional circuitry. Synaptic membrane events underlie this reconstruction: the connection between membranes is broken and reformed."}
{"id": "PMID:4659", "title": "Preliminary characterization of the acetylcholine receptor in human erythrocytes.", "content": "The response of human erythrocytes to cholinergic ligands was studied with an electron spin resonance assay. The membrane response to carbamyl choline was found to be antagonized by atropine and, in the absence of calcium, by tetrodotoxin. Experiments with resealed ghosts showed that the membrane response to carbamyl choline required ATP and calcium. Reductive alkylation of intact cells eliminated the cholinergic response, but the presence of saturating amounts of carbamyl choline protected the putative receptor against inactivation. Affinity labeling was used to demonstrate an apparent molecular weight of 41,000 for the carbamyl choline-binding species. A lipid vesicle extraction technique was used to induce a specific cation permeability defect in intact cells. Preliminary investigation of this phenomenon is described.", "contents": "Preliminary characterization of the acetylcholine receptor in human erythrocytes. The response of human erythrocytes to cholinergic ligands was studied with an electron spin resonance assay. The membrane response to carbamyl choline was found to be antagonized by atropine and, in the absence of calcium, by tetrodotoxin. Experiments with resealed ghosts showed that the membrane response to carbamyl choline required ATP and calcium. Reductive alkylation of intact cells eliminated the cholinergic response, but the presence of saturating amounts of carbamyl choline protected the putative receptor against inactivation. Affinity labeling was used to demonstrate an apparent molecular weight of 41,000 for the carbamyl choline-binding species. A lipid vesicle extraction technique was used to induce a specific cation permeability defect in intact cells. Preliminary investigation of this phenomenon is described."}
{"id": "PMID:4660", "title": "Effect of alcohol on elicited male sexual response.", "content": "Sixteen young men drunk three doses of alcohol and their sexual arousal was measured by the changes in penile diameter. The lowest alcohol dose (BAC of 0.025%) was associated with maximum penile diameter increase; marked suppression of response was found at BACs of 0.05% and above.", "contents": "Effect of alcohol on elicited male sexual response. Sixteen young men drunk three doses of alcohol and their sexual arousal was measured by the changes in penile diameter. The lowest alcohol dose (BAC of 0.025%) was associated with maximum penile diameter increase; marked suppression of response was found at BACs of 0.05% and above."}
{"id": "PMID:4661", "title": "\"Feeling no pain\" differential responses to pain by alcoholics and nonalcoholics before and after drinking.", "content": "Whisky reduced the level of pain reported by alcoholics but had no effect on that reported by nonalcoholics. The results appear to be based on the joint effects of the alcoholic's expectation that alcohol has an analgesic effect and the physiological cues accompanying alcohol consumption.", "contents": "\"Feeling no pain\" differential responses to pain by alcoholics and nonalcoholics before and after drinking. Whisky reduced the level of pain reported by alcoholics but had no effect on that reported by nonalcoholics. The results appear to be based on the joint effects of the alcoholic's expectation that alcohol has an analgesic effect and the physiological cues accompanying alcohol consumption."}
{"id": "PMID:4662", "title": "Decrease of iconic memory after alcohol.", "content": "Alcohol did not alter the rate of information loss from iconic memory. However, there was a dose-related decrease in the total amount of information reported which was independent of the rate of information loss.", "contents": "Decrease of iconic memory after alcohol. Alcohol did not alter the rate of information loss from iconic memory. However, there was a dose-related decrease in the total amount of information reported which was independent of the rate of information loss."}
{"id": "PMID:4663", "title": "The relationship between alcohol dosage and performance decrement in humans.", "content": "The effects of alcohol on human perceptual, cognitive and motor performance was assessed in a battery of tests, and the dose-response relationships for alcohol, important for the study of drug-alcohol interactions, established.", "contents": "The relationship between alcohol dosage and performance decrement in humans. The effects of alcohol on human perceptual, cognitive and motor performance was assessed in a battery of tests, and the dose-response relationships for alcohol, important for the study of drug-alcohol interactions, established."}
{"id": "PMID:4664", "title": "Personality impairment in alcoholism. Its relation to regional cerebral blood flow and psychometric performance.", "content": "The psychiatric symptoms constituting three main syndromes of personality impairment (\"defense,\" \"low vitality\" and \"emotional deficiency\") were homogeneous in alcoholic patients. Only the \"low vitality\" syndrome was associated with impaired psychometric performance and reduced cerebral blood flow.", "contents": "Personality impairment in alcoholism. Its relation to regional cerebral blood flow and psychometric performance. The psychiatric symptoms constituting three main syndromes of personality impairment (\"defense,\" \"low vitality\" and \"emotional deficiency\") were homogeneous in alcoholic patients. Only the \"low vitality\" syndrome was associated with impaired psychometric performance and reduced cerebral blood flow."}
{"id": "PMID:4665", "title": "Group assertiveness training for alcoholics.", "content": "Six men alcoholics showed increased assertiveness and improvement in social and occupational status after attending a group assertiveness training program.", "contents": "Group assertiveness training for alcoholics. Six men alcoholics showed increased assertiveness and improvement in social and occupational status after attending a group assertiveness training program."}
{"id": "PMID:4666", "title": "Viability of cells in ethanol. Role of alcohol dehydrogenase.", "content": "Rodent cells were found to contain a high level of alcohol dehydrogenase activity which was not inducible. Other hepatoma and nonhepatoma cell lines were tested and found to contain lower but measurable levels of alcohol dehydrogenase.", "contents": "Viability of cells in ethanol. Role of alcohol dehydrogenase. Rodent cells were found to contain a high level of alcohol dehydrogenase activity which was not inducible. Other hepatoma and nonhepatoma cell lines were tested and found to contain lower but measurable levels of alcohol dehydrogenase."}
{"id": "PMID:4668", "title": "Alcohol-induced conditioned taste aversion in rats. Effect of concentration and prior exposure to alcohol.", "content": "The effects of prior opportunities to drink alcohol solutions on the subsequent production of conditioned taste aversion by the oral ingestion of alcohol were evaluated. The consumption of 5 and 7% alcohol solutions produced conditioned aversion; the consumption of 3% alcohol solution did not result in aversion. Prior exposure to alcohol did not alter the extent of the aversion.", "contents": "Alcohol-induced conditioned taste aversion in rats. Effect of concentration and prior exposure to alcohol. The effects of prior opportunities to drink alcohol solutions on the subsequent production of conditioned taste aversion by the oral ingestion of alcohol were evaluated. The consumption of 5 and 7% alcohol solutions produced conditioned aversion; the consumption of 3% alcohol solution did not result in aversion. Prior exposure to alcohol did not alter the extent of the aversion."}
{"id": "PMID:4667", "title": "Plasma immunoreactive insulin and somatotropin in delirium tremens and alcoholic hallucinosis.", "content": "The glucose tolerance curve in alcoholics in delirium tremens was similar to that seen in hepatogenic diabetes. The secretion of immunoreactive insulin and somatotropin after glucose was similar in patients with delirium tremens and alcoholic hallucinosis.", "contents": "Plasma immunoreactive insulin and somatotropin in delirium tremens and alcoholic hallucinosis. The glucose tolerance curve in alcoholics in delirium tremens was similar to that seen in hepatogenic diabetes. The secretion of immunoreactive insulin and somatotropin after glucose was similar in patients with delirium tremens and alcoholic hallucinosis."}
{"id": "PMID:4669", "title": "Alcohol toxicity, blood alcohol concentration and body water in young and adult rats.", "content": "Young rats, with more body water, had lower blood alcohol concentrations than did older ones at several times after various doses. The young also recovered sooner from intoxication. The age difference in recovery increased with increasing dose.", "contents": "Alcohol toxicity, blood alcohol concentration and body water in young and adult rats. Young rats, with more body water, had lower blood alcohol concentrations than did older ones at several times after various doses. The young also recovered sooner from intoxication. The age difference in recovery increased with increasing dose."}
{"id": "PMID:4670", "title": "Estimated U.S. alcoholic beverage consumption, 1790-1860.", "content": "From 1790 to 1830 American consumption of alcoholic beverages generally rose, with an increased use of spirits, a high but declining consumption of hard cider, and a negligible intake of wine and beer. Intake of absolute alcohol peaked in 1830, at a rate twice that estimated for 1970. From 1830 to 1860 consumption fell sharply, but since 1860 consumption has fluctuated much less.", "contents": "Estimated U.S. alcoholic beverage consumption, 1790-1860. From 1790 to 1830 American consumption of alcoholic beverages generally rose, with an increased use of spirits, a high but declining consumption of hard cider, and a negligible intake of wine and beer. Intake of absolute alcohol peaked in 1830, at a rate twice that estimated for 1970. From 1830 to 1860 consumption fell sharply, but since 1860 consumption has fluctuated much less."}
{"id": "PMID:4671", "title": "Philosophies for educating about alcohol and other mood-modifying substance. Personal or social controls.", "content": "Groups of students, teachers, adult advisers to youth, civil-service supervisors and occupational-program consultants were in basic agreement on philosophies for educating about alcohol, marihuana, lysergide (LSD) and heroin.", "contents": "Philosophies for educating about alcohol and other mood-modifying substance. Personal or social controls. Groups of students, teachers, adult advisers to youth, civil-service supervisors and occupational-program consultants were in basic agreement on philosophies for educating about alcohol, marihuana, lysergide (LSD) and heroin."}
{"id": "PMID:4672", "title": "Drinking during pregnancy.", "content": "Pregnant women reported a decrease in the use of alcoholic beverages during pregnancy, often citing adverse physiological effects as a reason for the decline.", "contents": "Drinking during pregnancy. Pregnant women reported a decrease in the use of alcoholic beverages during pregnancy, often citing adverse physiological effects as a reason for the decline."}
{"id": "PMID:4676", "title": "The APUD cell concept.", "content": "Embryonic neural crest cells have been traced to the primitive entoderm where they differentiate into a family of hormone-producing cells, APUD cells. The APUD cell concept explains many otherwise seemingly dissociated clinical circumstances involving endocrine glands and hormone production by tumors.", "contents": "The APUD cell concept. Embryonic neural crest cells have been traced to the primitive entoderm where they differentiate into a family of hormone-producing cells, APUD cells. The APUD cell concept explains many otherwise seemingly dissociated clinical circumstances involving endocrine glands and hormone production by tumors."}
{"id": "PMID:4679", "title": "Effect of narcotic analgesics on the striatal homovanillic acid content in mice; relation to antinociceptive effect.", "content": "The effects of various narcotic analgesics on striatal homovanillic acid (HVA) content, hot plate time and rectal temperature in mice were compared in relation to dose and time. The hypothermia induced by narcotic analgesics did not correlate with the striat\"al HVA increase. Pentazocine, cyclazocine and thebaine had no effect on the hot plate time. The maximum prolongation of hot plate time induced by morphine, methadone or piminodine occurred before the highest HVA increase. The highest increase induced by narcotic analgesics in striatal HVA content was twice the original concentration. This occurred 2 hr after 40 mg/kg of morphine; 2 hr after 20 mg/kg of methadone; 1/2 hr after 20 mg/kg of piminodine; and 1 hr after 60 mg/kg of pentazocine. Cyclacozine (10 and 20 mg/kg) and thebaine (10 mg/kg) did not alter the HVA content. With the exception of pentazocine, those doses of narcotic analgesics that caused equal increases in striatal HVA content were also equianalgesic. These results suggest that there are similarities in the structural requirements for antinociceptive and striatal HVA-increasing effects of narcotic analgesics. The neuroleptic compound haloperidol (0.5 mg/kg) caused a fourfold increase in striatal HVA content making it twice as efficient as narcotic analgesics. This finding suggests that narcotic analgesics do not act on the same sites as neuroleptics when causing an increase in striatal HVA content.", "contents": "Effect of narcotic analgesics on the striatal homovanillic acid content in mice; relation to antinociceptive effect. The effects of various narcotic analgesics on striatal homovanillic acid (HVA) content, hot plate time and rectal temperature in mice were compared in relation to dose and time. The hypothermia induced by narcotic analgesics did not correlate with the striat\"al HVA increase. Pentazocine, cyclazocine and thebaine had no effect on the hot plate time. The maximum prolongation of hot plate time induced by morphine, methadone or piminodine occurred before the highest HVA increase. The highest increase induced by narcotic analgesics in striatal HVA content was twice the original concentration. This occurred 2 hr after 40 mg/kg of morphine; 2 hr after 20 mg/kg of methadone; 1/2 hr after 20 mg/kg of piminodine; and 1 hr after 60 mg/kg of pentazocine. Cyclacozine (10 and 20 mg/kg) and thebaine (10 mg/kg) did not alter the HVA content. With the exception of pentazocine, those doses of narcotic analgesics that caused equal increases in striatal HVA content were also equianalgesic. These results suggest that there are similarities in the structural requirements for antinociceptive and striatal HVA-increasing effects of narcotic analgesics. The neuroleptic compound haloperidol (0.5 mg/kg) caused a fourfold increase in striatal HVA content making it twice as efficient as narcotic analgesics. This finding suggests that narcotic analgesics do not act on the same sites as neuroleptics when causing an increase in striatal HVA content."}
{"id": "PMID:4680", "title": "The role of new health practitioners in a prepaid group practice: provider differences in process and outcomes of medical care.", "content": "Practice patterns and patient-reported outcomes of care are compared in detail for ten physicians and 12 new health practitioners delivering ambulatory care in two departments of a prepaid group practice, the Columbia Medical Plan (CMP). All providers completed questionnaires for a 50 per cent random sample of patients seen during a two-week period. Patients completed questionnaires prior to receiving care and were interviewed one week and one month after their clinic visits. New health practitioners deliver approximately 75 per cent of well-person care, 56 per cent of problem-oriented care in adult medicine, and 29 per cent of problem care in pediatrics. They have become increasingly involved over time in the treatment of acute conditions and injuries while physicians have retained their predominant role in treating patients with chronic conditions. Thirty-two per cent of visits with new healh providers involved a physician in one or more of the following: decision-making, direct supervision, consultation, or seeing the patient as a second provider of care. Degree of autonomy varied by type of task performed, category of problem treated, and specialty. The following outcomes of care were examined by type of provider: patient-reported change in problem status,including frequency and intensity of pain or discomfort, level of anxiety, and degree of activity limitation; the degree to which physician-specified criteria for the most commonly occurring conditions were met with respect to change in problem status; and patient satisfaction with a number of dimensions of the clinic visit. The analysis suggests that the new health practitioners at the CMP are providing care, within their areas of responsibility, of comparable quality to that delivered by physicians.", "contents": "The role of new health practitioners in a prepaid group practice: provider differences in process and outcomes of medical care. Practice patterns and patient-reported outcomes of care are compared in detail for ten physicians and 12 new health practitioners delivering ambulatory care in two departments of a prepaid group practice, the Columbia Medical Plan (CMP). All providers completed questionnaires for a 50 per cent random sample of patients seen during a two-week period. Patients completed questionnaires prior to receiving care and were interviewed one week and one month after their clinic visits. New health practitioners deliver approximately 75 per cent of well-person care, 56 per cent of problem-oriented care in adult medicine, and 29 per cent of problem care in pediatrics. They have become increasingly involved over time in the treatment of acute conditions and injuries while physicians have retained their predominant role in treating patients with chronic conditions. Thirty-two per cent of visits with new healh providers involved a physician in one or more of the following: decision-making, direct supervision, consultation, or seeing the patient as a second provider of care. Degree of autonomy varied by type of task performed, category of problem treated, and specialty. The following outcomes of care were examined by type of provider: patient-reported change in problem status,including frequency and intensity of pain or discomfort, level of anxiety, and degree of activity limitation; the degree to which physician-specified criteria for the most commonly occurring conditions were met with respect to change in problem status; and patient satisfaction with a number of dimensions of the clinic visit. The analysis suggests that the new health practitioners at the CMP are providing care, within their areas of responsibility, of comparable quality to that delivered by physicians."}
{"id": "PMID:4681", "title": "Communication patterns of doctors and their assistants.", "content": "Communication patterns between physicians and their assistants (Medex) were observed in 19 practices to describe and evaluated the nature of their relationship. Observations demonstrated that interaction around patient problems was approximately 30 minures per day and informal, with the Medex more often initiating the contact. Medex were more likely to ask for, and physicians were more likely to give, suggestions. Physicians appeared to regard the accomplishment of the immediate task as more important than maintaining good relations. In most practices, supervision was available when requested. Generally, both the physician and the Medex show a striking similarity in communication styles.", "contents": "Communication patterns of doctors and their assistants. Communication patterns between physicians and their assistants (Medex) were observed in 19 practices to describe and evaluated the nature of their relationship. Observations demonstrated that interaction around patient problems was approximately 30 minures per day and informal, with the Medex more often initiating the contact. Medex were more likely to ask for, and physicians were more likely to give, suggestions. Physicians appeared to regard the accomplishment of the immediate task as more important than maintaining good relations. In most practices, supervision was available when requested. Generally, both the physician and the Medex show a striking similarity in communication styles."}
{"id": "PMID:4689", "title": "Sterol synthesis in the liver, intestine, and lung of the guinea pig.", "content": "The relative rates of sterol synthesis in the liver, ileum, and lung of the guinea pig have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into digitonin-precipitable sterols. The liver showed maximum incorporation of acetate at pH 6.5, the ileum at pH 7.5, and the lung at pH 6.0. The incorporation of acetate approached the maximum rate at a concentration of 10 mM with the liver and lung and 5 mM with the ileum. Using these conditions of assay, sterol synthesis was measured in the liver, ileum, and lung of four groups of guinea pigs killed at 6-hourly intervals. Depending on the time of day, the rate of sterol synthesis in the ileum was from 6 to 14 times that in the liver, while in the lung the rate was up to 3 times that shown by the liver, Additional studies showed that all regions of the small intestine synthesized sterol at a higher rate than the liver, with the highest rate of synthesis occurring in the ileum. The rates observed in the adrenal, testis, muscle, adipose tissue, and skin indicated that these tissues are not quantitatively important sites of sterol synthesis in the guinea pig.", "contents": "Sterol synthesis in the liver, intestine, and lung of the guinea pig. The relative rates of sterol synthesis in the liver, ileum, and lung of the guinea pig have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into digitonin-precipitable sterols. The liver showed maximum incorporation of acetate at pH 6.5, the ileum at pH 7.5, and the lung at pH 6.0. The incorporation of acetate approached the maximum rate at a concentration of 10 mM with the liver and lung and 5 mM with the ileum. Using these conditions of assay, sterol synthesis was measured in the liver, ileum, and lung of four groups of guinea pigs killed at 6-hourly intervals. Depending on the time of day, the rate of sterol synthesis in the ileum was from 6 to 14 times that in the liver, while in the lung the rate was up to 3 times that shown by the liver, Additional studies showed that all regions of the small intestine synthesized sterol at a higher rate than the liver, with the highest rate of synthesis occurring in the ileum. The rates observed in the adrenal, testis, muscle, adipose tissue, and skin indicated that these tissues are not quantitatively important sites of sterol synthesis in the guinea pig."}
{"id": "PMID:4693", "title": "Autoregulatory system of insulin degradation in liver. II. Relationship between blood insulin levels and GSH-dependent insulin degrading activity in liver and blood.", "content": "An autoregulatory system of insulin degradation in the liver in which the rate of insulin metabolism changes in response to fluctuation in its blood levels, was investigated. In the plasma of rats and man in the absence of reduced glutathione (GSH), insulin degradation was not observed, but when a sufficient amount of reduced glutathione was added, the plasma did degrade insulin. This GSH-dependent insulin degrading activity in plasma was quite similar to that in liver in its nature. In rats, this GSH-dependent insulin degrading activity in the liver and plasma was fluctuated in  response to fluctuation in the blood insulin levels, and the GSH-dependent insulin degrading activity in plasma was well correlated with that in the liver. Similarly, in man the GSH-dependent insulin degrading activity in plasma was changed in response to fluctuation in the blood insulin levels. In plasma under the physiologic conditions, there is an insufficient amount of reduced glutathione to elicit the insulin degrading activity, but in the liver there is a sufficient amount of reduced glutathione to manifest this activity. This evidence further supports the concept that an autoregulatory system of insulin degradation in the liver exists in man.", "contents": "Autoregulatory system of insulin degradation in liver. II. Relationship between blood insulin levels and GSH-dependent insulin degrading activity in liver and blood. An autoregulatory system of insulin degradation in the liver in which the rate of insulin metabolism changes in response to fluctuation in its blood levels, was investigated. In the plasma of rats and man in the absence of reduced glutathione (GSH), insulin degradation was not observed, but when a sufficient amount of reduced glutathione was added, the plasma did degrade insulin. This GSH-dependent insulin degrading activity in plasma was quite similar to that in liver in its nature. In rats, this GSH-dependent insulin degrading activity in the liver and plasma was fluctuated in  response to fluctuation in the blood insulin levels, and the GSH-dependent insulin degrading activity in plasma was well correlated with that in the liver. Similarly, in man the GSH-dependent insulin degrading activity in plasma was changed in response to fluctuation in the blood insulin levels. In plasma under the physiologic conditions, there is an insufficient amount of reduced glutathione to elicit the insulin degrading activity, but in the liver there is a sufficient amount of reduced glutathione to manifest this activity. This evidence further supports the concept that an autoregulatory system of insulin degradation in the liver exists in man."}
{"id": "PMID:4722", "title": "Envelope mutation promoting autolysis in Salmonella typhimurium.", "content": "Two strains independently isolated in Salmonella typhimurium display abnormal autolytic activity when nutrient broth becomes alkaline. They also show increased sensitivity to deoxycholate, EDTA, and sodium dodecyl sulfate. Response to acridine orange remains normal. In both strains a single stable mutation is responsible for all the changes. The same gene, called envD, appears to be involved in both mutant strains. envD has been located at minute 33 of the Salmonella genetic map, between markers sucA and nadA, very close to the latter. envD also affects morphological characteristics of the cells. Many mutant cells are shorter than wild type bacteria, and appear frequently associated in short chains of 4 to 10 cells. Furthermore, envD mutants display division by septation under conditions that preclude its observation in wild type strains.", "contents": "Envelope mutation promoting autolysis in Salmonella typhimurium. Two strains independently isolated in Salmonella typhimurium display abnormal autolytic activity when nutrient broth becomes alkaline. They also show increased sensitivity to deoxycholate, EDTA, and sodium dodecyl sulfate. Response to acridine orange remains normal. In both strains a single stable mutation is responsible for all the changes. The same gene, called envD, appears to be involved in both mutant strains. envD has been located at minute 33 of the Salmonella genetic map, between markers sucA and nadA, very close to the latter. envD also affects morphological characteristics of the cells. Many mutant cells are shorter than wild type bacteria, and appear frequently associated in short chains of 4 to 10 cells. Furthermore, envD mutants display division by septation under conditions that preclude its observation in wild type strains."}
{"id": "PMID:4727", "title": "Ferredoxin-dependent photosynthetic reduction of nitrate and nitrite by particles of Anacystis nidulans.", "content": "The dark and light reduction of nitrate and nitrite by cell-free preparations of the blue-green alga Anacystis nidulans has been investigated. The three following methods have been successfully applied to the preparation of active particulate fractions from the alga cells: (a) shaking with glass beads, (b) lysozyme treatment and lysis of the resulting protoplasts, and (c) sonication. The two enzymes of the nitrate-reducing system-namely, nitrate reductase and nitrite reductase-are firmly bound to the isolated pigment-containing particles, and can be easily solubilized by prolonging the vibration or sonication time. Both enzymes-whether solubilized or bound to the particles-depend on reduced ferredoxin as the immediate electron donor. In its presence, the alga particles catalyze the gradual photoreduction of nitrate to nitrite and ammonia, a process that can thus be considered as one of the most simple and relevant examples of Photosynthesis. Some of the properties of nitrate reductase have been studied. Nitrate reductase as well as nitrite reductase are adaptive enzymes repressed by ammonia.", "contents": "Ferredoxin-dependent photosynthetic reduction of nitrate and nitrite by particles of Anacystis nidulans. The dark and light reduction of nitrate and nitrite by cell-free preparations of the blue-green alga Anacystis nidulans has been investigated. The three following methods have been successfully applied to the preparation of active particulate fractions from the alga cells: (a) shaking with glass beads, (b) lysozyme treatment and lysis of the resulting protoplasts, and (c) sonication. The two enzymes of the nitrate-reducing system-namely, nitrate reductase and nitrite reductase-are firmly bound to the isolated pigment-containing particles, and can be easily solubilized by prolonging the vibration or sonication time. Both enzymes-whether solubilized or bound to the particles-depend on reduced ferredoxin as the immediate electron donor. In its presence, the alga particles catalyze the gradual photoreduction of nitrate to nitrite and ammonia, a process that can thus be considered as one of the most simple and relevant examples of Photosynthesis. Some of the properties of nitrate reductase have been studied. Nitrate reductase as well as nitrite reductase are adaptive enzymes repressed by ammonia."}
{"id": "PMID:4728", "title": "Appearance of a syndrome similar to graft versus host reaction in C57 B1/6 mice bearing skin allogenic graft.", "content": "A syndrome similar to GVHR is described in mice of C57B1/6 strain during the WHT/Ht skin allografts rejection period. In all the cases the described thymus involution was associated with the hypertrophy of lymph nodes. Their volume increase is due to the high number of blastic pyroninophilic and plasma cells concomitant with small lymphocytes depletion in the cortical area, and with a very pronounced hypertrophy of medullary cords by presence of a high number of plasmocytes and blastic cells. These changes have been noticed only in some animals sacrified during the first days after grafting and never later one. In agreement with the scarce data of the literature, we think that the immunocompetent passenger lymphocyte comprised in the skin grafts constitute an immunologic organ able to induce a GVHR at the beginning of the period of graft survival on the host. This GVHR, generally mild and without clinical and microscopic signs, becomes obvious only in animals which, for unknown reasons, present a low immunologic defense capacity. In these animals the described process seems to be reversible.", "contents": "Appearance of a syndrome similar to graft versus host reaction in C57 B1/6 mice bearing skin allogenic graft. A syndrome similar to GVHR is described in mice of C57B1/6 strain during the WHT/Ht skin allografts rejection period. In all the cases the described thymus involution was associated with the hypertrophy of lymph nodes. Their volume increase is due to the high number of blastic pyroninophilic and plasma cells concomitant with small lymphocytes depletion in the cortical area, and with a very pronounced hypertrophy of medullary cords by presence of a high number of plasmocytes and blastic cells. These changes have been noticed only in some animals sacrified during the first days after grafting and never later one. In agreement with the scarce data of the literature, we think that the immunocompetent passenger lymphocyte comprised in the skin grafts constitute an immunologic organ able to induce a GVHR at the beginning of the period of graft survival on the host. This GVHR, generally mild and without clinical and microscopic signs, becomes obvious only in animals which, for unknown reasons, present a low immunologic defense capacity. In these animals the described process seems to be reversible."}
{"id": "PMID:4729", "title": "[Mycoplasma-like micro-organisms in malignant tumors and non-tumours dermatovenerological diseases. Electron microscopic investigations (author's transl)].", "content": "In examination of the ultrastructure of excised tissue and other material from patients with various diseases, principally dermatovenerological affections and with malignant tumors, and in healthy control subjects, patterns suggesting mycoplasma were repeatedly found in certain diseases only. Specific attempts to isolate mycoplasma from the material were made, in which previously patterns of a mycoplasma type had frequently been seen. It was possible to culture mycoplasma-like organisms in vitro from patients with the following diseases: malignant melanoma, mycosis fungoides, prickle cell carcinoma, squamous cell carcinoma, non-specific urethritis, pemphigus erythematosus, panarteritis nodosa and vasculitis allergica cutis.", "contents": "[Mycoplasma-like micro-organisms in malignant tumors and non-tumours dermatovenerological diseases. Electron microscopic investigations (author's transl)]. In examination of the ultrastructure of excised tissue and other material from patients with various diseases, principally dermatovenerological affections and with malignant tumors, and in healthy control subjects, patterns suggesting mycoplasma were repeatedly found in certain diseases only. Specific attempts to isolate mycoplasma from the material were made, in which previously patterns of a mycoplasma type had frequently been seen. It was possible to culture mycoplasma-like organisms in vitro from patients with the following diseases: malignant melanoma, mycosis fungoides, prickle cell carcinoma, squamous cell carcinoma, non-specific urethritis, pemphigus erythematosus, panarteritis nodosa and vasculitis allergica cutis."}
{"id": "PMID:4730", "title": "[Chemical Investigation of Chronic Pancreatitis].", "content": "We differentiate indirect and direct methods. The indirect methods include the examination of the blood (ESR, blood picture, electrolytes, especially calcium, for the exclusion of hyperparathyroidism, status of fat and liver enzymes, activity of alpha-amylase and lipase. More informative than a serum determination is the measurement of the amylase activity in the 24-hour urine. The detection of chymotrypsin in the stool can be recommended as an investigative test also for use in general practive in collaboration with a central laboratory.- The direct methods include investigation of the duodenal juice with measurement of pH, bicarbonate, of the activities of chymotrypsin, trypsin, lipase and amylase. For excluding of a disturbance of the carbohydrate metabolism in addition to blood sugar determinations, glucose tolerance and tolbutamide tests, the determination of insulin activity is indicated.", "contents": "[Chemical Investigation of Chronic Pancreatitis]. We differentiate indirect and direct methods. The indirect methods include the examination of the blood (ESR, blood picture, electrolytes, especially calcium, for the exclusion of hyperparathyroidism, status of fat and liver enzymes, activity of alpha-amylase and lipase. More informative than a serum determination is the measurement of the amylase activity in the 24-hour urine. The detection of chymotrypsin in the stool can be recommended as an investigative test also for use in general practive in collaboration with a central laboratory.- The direct methods include investigation of the duodenal juice with measurement of pH, bicarbonate, of the activities of chymotrypsin, trypsin, lipase and amylase. For excluding of a disturbance of the carbohydrate metabolism in addition to blood sugar determinations, glucose tolerance and tolbutamide tests, the determination of insulin activity is indicated."}
{"id": "PMID:4733", "title": "Huntington's chorea. Changes in neurotransmitter receptors in the brain.", "content": "Neurotransmitter-receptor binding sites for apparent muscarinic cholinergic, beta-adrenergic, gamma-aminobutyric acid and serotonin receptors were measured in the caudate nucleus and frontal cerebral cortex from post-mortem brains of 16 patients with Huntington's chorea and 16 controls. In addition, the samples were assayed for the gamma-aminobutyric-acid-synthesizing enzyme, glutamic acid decarboxylase, and for the acetylcholine-synthesizing enzyme, choline acetyltransferase. In the caudate nucleus of choreic brain, both enzyme activities were markedly lower, with significant decreases in muscarinic cholinergic and serotonin receptor binding, whereas enzyme activities and receptor binding were unchanged in the cerebral cortex. By contrast, gamma-aminobutyric acid and beta-adrenergic receptor binding were not significantly different in choreic and control caudate nucleus or cortex, suggesting that, despite the loss of gamma-aminobutyric-acid-synthesizing ability in the corpus striatum, gamma-aminobuytric acid mimetic drugs might alleviate the movement disorders in Huntington's chorea.", "contents": "Huntington's chorea. Changes in neurotransmitter receptors in the brain. Neurotransmitter-receptor binding sites for apparent muscarinic cholinergic, beta-adrenergic, gamma-aminobutyric acid and serotonin receptors were measured in the caudate nucleus and frontal cerebral cortex from post-mortem brains of 16 patients with Huntington's chorea and 16 controls. In addition, the samples were assayed for the gamma-aminobutyric-acid-synthesizing enzyme, glutamic acid decarboxylase, and for the acetylcholine-synthesizing enzyme, choline acetyltransferase. In the caudate nucleus of choreic brain, both enzyme activities were markedly lower, with significant decreases in muscarinic cholinergic and serotonin receptor binding, whereas enzyme activities and receptor binding were unchanged in the cerebral cortex. By contrast, gamma-aminobutyric acid and beta-adrenergic receptor binding were not significantly different in choreic and control caudate nucleus or cortex, suggesting that, despite the loss of gamma-aminobutyric-acid-synthesizing ability in the corpus striatum, gamma-aminobuytric acid mimetic drugs might alleviate the movement disorders in Huntington's chorea."}
{"id": "PMID:4739", "title": "[The effect of changes in the pH of the external solution on the afterpotentials of individual frog nodes of Ranvier].", "content": "A decrease in pH to 5 elicited a small increase in afterdepolarization of a single Ranvier node and an increase in pH to 9 had no effect. Post-tetanic hyperpolarization decreases at pH 5 and its duration somewhat increases. An increase in pH to 9 also had no effect. Similar changes in afterdepolarization and post-tetanic hyperpolarization were observed in potassium free solutions. A conclusion is made that changes in afterpotentials are determined by changes in kinetics of the membrane potassium permeability.", "contents": "[The effect of changes in the pH of the external solution on the afterpotentials of individual frog nodes of Ranvier]. A decrease in pH to 5 elicited a small increase in afterdepolarization of a single Ranvier node and an increase in pH to 9 had no effect. Post-tetanic hyperpolarization decreases at pH 5 and its duration somewhat increases. An increase in pH to 9 also had no effect. Similar changes in afterdepolarization and post-tetanic hyperpolarization were observed in potassium free solutions. A conclusion is made that changes in afterpotentials are determined by changes in kinetics of the membrane potassium permeability."}
{"id": "PMID:4744", "title": "Prolonged clinical and experimental follow-up of hospitalized schizophrenics.", "content": "148 chronic schizophrenics admitted between 1938 and 1961 had previously been followed up. In 1972, they were re-examined, on the average 10 years after the first follow-up. 44 belonged to a series of patients studied between 1955 and 1957 with a battery of conditional reflex tests. The patients belonging to the experimental series were retested with word associations. From an experimental point of view the patients performed better over the prolonged observation period. The clinical state also showed improvement. A comparison of the chronic hospital population during 1955-57 and 1972-74 suggests that the new chronics present much less of the severe schizophrenic deterioration than the old ones. They also have remarkably better verbal functions these changes are assumed to be mainly due to drug treatment. The beneficial effects of drugs appear to come mainly within the first 2 years.", "contents": "Prolonged clinical and experimental follow-up of hospitalized schizophrenics. 148 chronic schizophrenics admitted between 1938 and 1961 had previously been followed up. In 1972, they were re-examined, on the average 10 years after the first follow-up. 44 belonged to a series of patients studied between 1955 and 1957 with a battery of conditional reflex tests. The patients belonging to the experimental series were retested with word associations. From an experimental point of view the patients performed better over the prolonged observation period. The clinical state also showed improvement. A comparison of the chronic hospital population during 1955-57 and 1972-74 suggests that the new chronics present much less of the severe schizophrenic deterioration than the old ones. They also have remarkably better verbal functions these changes are assumed to be mainly due to drug treatment. The beneficial effects of drugs appear to come mainly within the first 2 years."}
{"id": "PMID:4759", "title": "[The state of prothrombin, plasminogen and fibrinogen in the newborn infant].", "content": "The esterase activity of thrombin and plasmin on artificial substrates was used to study the kinetics of these enzymes by Lineweaver and Burk's method. In the plasma of new-born infants, plasmin obtained from streptokinase has an avidity comparable with that in adults. Thrombin is obtained by the action of staphylocoagulase and taipan venom. Its avidity has important individual variations and is different from that in adults. An inhibitor is present both in the plasma and in the serum of the new-born. Fibrinogen was studied by variations in absorption of light during coagulation by thrombin. The abnormalities observed depend on the physical and clinical conditions of the medium (ph, osmolality). These characteristics depend on the age of the infant, but also seem to depend on the conditions of the sample and, in particular, on fibrinolytic reactions. The existence of foetal fibrinogen is discussed.", "contents": "[The state of prothrombin, plasminogen and fibrinogen in the newborn infant]. The esterase activity of thrombin and plasmin on artificial substrates was used to study the kinetics of these enzymes by Lineweaver and Burk's method. In the plasma of new-born infants, plasmin obtained from streptokinase has an avidity comparable with that in adults. Thrombin is obtained by the action of staphylocoagulase and taipan venom. Its avidity has important individual variations and is different from that in adults. An inhibitor is present both in the plasma and in the serum of the new-born. Fibrinogen was studied by variations in absorption of light during coagulation by thrombin. The abnormalities observed depend on the physical and clinical conditions of the medium (ph, osmolality). These characteristics depend on the age of the infant, but also seem to depend on the conditions of the sample and, in particular, on fibrinolytic reactions. The existence of foetal fibrinogen is discussed."}
{"id": "PMID:4760", "title": "Local renal graft-versus-host reaction: sequential ultrastructural study.", "content": "A sequential study has been made of the ultrastructure of local renal graft-versus-host reactions produced in cyclophosphamide-pretreated rats by injection of either allogeneic or xenogeneic (mouse) spleen cells beneath the renal capsule. Early in the reaction, immunoblasts were seen between the outer cortical tubules, and there was associated interstitial oedema and tubular degeneration. In places, several small lymphocytes were observed clustered around and in close cytoplasmic contact with individual immunoblasts, perhaps representing interaction between donor and host cells. As the reaction proceeded, the number of lymphoid cells increased by immigration from peritubular vessels. Some tubules were invaded by lymphocytes but this was not closely related to the development of tubular injury. The reaction was maximum at one week and then decreased. Now, there was greater diversity of cells including macrophages, plasma cells and eosinophils, while many lymphoid cells became necrotic. It is concluded that most of the renal parenchymal injury is due to chemical mediators liberated from the infiltrating cells rather than to ischaemia or direct cytoplasmic interaction between leucocytes and tubular epithelium.", "contents": "Local renal graft-versus-host reaction: sequential ultrastructural study. A sequential study has been made of the ultrastructure of local renal graft-versus-host reactions produced in cyclophosphamide-pretreated rats by injection of either allogeneic or xenogeneic (mouse) spleen cells beneath the renal capsule. Early in the reaction, immunoblasts were seen between the outer cortical tubules, and there was associated interstitial oedema and tubular degeneration. In places, several small lymphocytes were observed clustered around and in close cytoplasmic contact with individual immunoblasts, perhaps representing interaction between donor and host cells. As the reaction proceeded, the number of lymphoid cells increased by immigration from peritubular vessels. Some tubules were invaded by lymphocytes but this was not closely related to the development of tubular injury. The reaction was maximum at one week and then decreased. Now, there was greater diversity of cells including macrophages, plasma cells and eosinophils, while many lymphoid cells became necrotic. It is concluded that most of the renal parenchymal injury is due to chemical mediators liberated from the infiltrating cells rather than to ischaemia or direct cytoplasmic interaction between leucocytes and tubular epithelium."}
{"id": "PMID:4765", "title": "Functional abnormalities in renal cystic diseases.", "content": "The functions of a kidney, whether normal or cystic, can be conceptualized in terms of anatomy (glomerulus, proximal tubule, loop of Henle, distal convolution, and collecting duct), activity (volume regulation, dilution and concentration, acid-base regulation, potassium excretion, transport of organic molecules, and calcium and phosphate excretion), and the integration of anatomic organization to meet functional demand. Our discussion of renal cystic disorders follows this conceptual outline. For discussions of normal renal physiology, the reader is referred to any one of several recent, excellent reviews (1-3). Systematic evaluation of renal function in cystic diseases of the kidney (medullary sponge kidney, medullary cystic disease, and polycystic kidney disease) has only rarely been performed. The available information suggests that the earliest detectable lesions consist primarily of tubular dysfunction. With time, however, significant reduction of glomerular filtration occurs and the resultant accumulation of uremic toxins dominates the clinical picture in polycystic and medullary cystic disease. Significant changes in glomerular function are unusual in medullary sponge kidney. This review represents an attempt to summarize the large body of literature that has accumulated on functional abnormalities in these disorders, and to point out those areas where further investigations are needed.", "contents": "Functional abnormalities in renal cystic diseases. The functions of a kidney, whether normal or cystic, can be conceptualized in terms of anatomy (glomerulus, proximal tubule, loop of Henle, distal convolution, and collecting duct), activity (volume regulation, dilution and concentration, acid-base regulation, potassium excretion, transport of organic molecules, and calcium and phosphate excretion), and the integration of anatomic organization to meet functional demand. Our discussion of renal cystic disorders follows this conceptual outline. For discussions of normal renal physiology, the reader is referred to any one of several recent, excellent reviews (1-3). Systematic evaluation of renal function in cystic diseases of the kidney (medullary sponge kidney, medullary cystic disease, and polycystic kidney disease) has only rarely been performed. The available information suggests that the earliest detectable lesions consist primarily of tubular dysfunction. With time, however, significant reduction of glomerular filtration occurs and the resultant accumulation of uremic toxins dominates the clinical picture in polycystic and medullary cystic disease. Significant changes in glomerular function are unusual in medullary sponge kidney. This review represents an attempt to summarize the large body of literature that has accumulated on functional abnormalities in these disorders, and to point out those areas where further investigations are needed."}
{"id": "PMID:4766", "title": "Phosphate transport by isolated renal brush border vesicles.", "content": "A sodium dependent specific transport system for phosphate is present in the brush border microvilli but absent from the basal-lateral plasma membranes. The apparent affinity of this transport system for phosphate is 0.08 mM at 100 mM sodium and pH 7.4. It is inhibited competitively by arsenate with an apparent inhibitor constant of 1.1 mM (100 mM sodium, pH 7.4). Sodium dependent phosphate uptake is two times higher at pH 8 compared to the uptake observed at pH 6. The apparent affinity of the transport system for sodium is also pH-dependent, half-maximal stimulation of uptake is found at pH 6 with 129 mM sodium, at pH 7.4 with 60 mM sodium and at pH 8 with 50 mM sodium. Under all conditions a nonhyperbolic dependence of phosphate uptake on the sodium concentration is observed. The uptake of phosphate by brush border microvilli vesicles shows a typical overshoot phenomenon in the presence of sodium gradient across the membrane (CNao greater than CNai). The amount of pohsphate taken up after 2 min is about twice the equilibrium value reached after 2 h of incubation. At pH 7.4 the initial rate of uptake is increased only slighyly (12%) by inside negative membrane diffusion potentials and inhibited to the same extent by inside positive membrane diffusion potentials. These results indicate that the entry of phosphate across the brush border membrane into the epithelial cell of the proximal tubule is coupled to the entry of sodium. The transfer of phosphate is dependent on its concentration gradient and on the concentration difference of sodium. The data are best explained by the following hypothesis: Both the primary phosphate as well as the secondary phosphate are transported in cotransport with sodium. The divalent form however seems to be transported preferentially. Its transport occurs electroneutral with 2 sodium ions; the monovalent phosphate also enters the cell together with 2 sodium ions but as a positively charged complex. The exit of phosphate across the contraluminal cell border is sodium independent and is favoured by the high intracellular phosphate concentration and the inside negative membrane potential.", "contents": "Phosphate transport by isolated renal brush border vesicles. A sodium dependent specific transport system for phosphate is present in the brush border microvilli but absent from the basal-lateral plasma membranes. The apparent affinity of this transport system for phosphate is 0.08 mM at 100 mM sodium and pH 7.4. It is inhibited competitively by arsenate with an apparent inhibitor constant of 1.1 mM (100 mM sodium, pH 7.4). Sodium dependent phosphate uptake is two times higher at pH 8 compared to the uptake observed at pH 6. The apparent affinity of the transport system for sodium is also pH-dependent, half-maximal stimulation of uptake is found at pH 6 with 129 mM sodium, at pH 7.4 with 60 mM sodium and at pH 8 with 50 mM sodium. Under all conditions a nonhyperbolic dependence of phosphate uptake on the sodium concentration is observed. The uptake of phosphate by brush border microvilli vesicles shows a typical overshoot phenomenon in the presence of sodium gradient across the membrane (CNao greater than CNai). The amount of pohsphate taken up after 2 min is about twice the equilibrium value reached after 2 h of incubation. At pH 7.4 the initial rate of uptake is increased only slighyly (12%) by inside negative membrane diffusion potentials and inhibited to the same extent by inside positive membrane diffusion potentials. These results indicate that the entry of phosphate across the brush border membrane into the epithelial cell of the proximal tubule is coupled to the entry of sodium. The transfer of phosphate is dependent on its concentration gradient and on the concentration difference of sodium. The data are best explained by the following hypothesis: Both the primary phosphate as well as the secondary phosphate are transported in cotransport with sodium. The divalent form however seems to be transported preferentially. Its transport occurs electroneutral with 2 sodium ions; the monovalent phosphate also enters the cell together with 2 sodium ions but as a positively charged complex. The exit of phosphate across the contraluminal cell border is sodium independent and is favoured by the high intracellular phosphate concentration and the inside negative membrane potential."}
{"id": "PMID:4767", "title": "The effect of carbonic anhydrase inhibition on bicarbonate reabsorption.", "content": "Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion.", "contents": "The effect of carbonic anhydrase inhibition on bicarbonate reabsorption. Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion."}
{"id": "PMID:4779", "title": "Atherosclerotic cerebral infarction: pathophysiologic aspects.", "content": "When the supply of substrate to the brain is threatened, homeostatic mechanisms induce cerebral vasodilatation to compensate for the insufficiency. When a region of the brain is rendered completely ischemic, local infarction occurs. The size of the infarct depends partly on the availability of collateral circulation and the adequacy of the homeostatic mechanisms controlling blood flow in stillpatent vessels. Several approaches to acute-phase treatment of stroke derive from clinical and experimental studies of cerebral blood flow and metabolism. We must conclude that both surgical and nonsurgical therapeutic measures have been of limited value in the treatment of cerebral infarction and that the basic therapy for completed stroke remains good medical management of complications and attentive nursing care.", "contents": "Atherosclerotic cerebral infarction: pathophysiologic aspects. When the supply of substrate to the brain is threatened, homeostatic mechanisms induce cerebral vasodilatation to compensate for the insufficiency. When a region of the brain is rendered completely ischemic, local infarction occurs. The size of the infarct depends partly on the availability of collateral circulation and the adequacy of the homeostatic mechanisms controlling blood flow in stillpatent vessels. Several approaches to acute-phase treatment of stroke derive from clinical and experimental studies of cerebral blood flow and metabolism. We must conclude that both surgical and nonsurgical therapeutic measures have been of limited value in the treatment of cerebral infarction and that the basic therapy for completed stroke remains good medical management of complications and attentive nursing care."}
{"id": "PMID:4780", "title": "Pharmacologic therapy of asthma.", "content": "Asthma is treated by avoiding the precipitants of symptoms, by a trial of hyposensitization (immunotherapy) if the precipitant cannot be avoided, and principally by pharmacologic therapy. Acute attacks have been most widely treated with epinephrine, but adrenergic aerosol bronchodilators and aminophylline are being used increasingly. When an acute attack of asthma does not respond to treatment, a diagnosis of status asthmaticus should be considered and the patient treated in a hospital intensive care unit because of the potentially life-threatening sequela of respiratory failure. Periodic mild episodes of asthma usually respond to administration of an oral bronchodilator. Chronic low-grade asthma is best treated with an around-the-clock regimen of theophylline. Patients whose asthma is not under satisfactory control with conventional bronchodilators may be given a trial of cromolyn sodium. Chronic severe cases may be treated with corticosteroids, but these drugs must be skillfully administered to avoid adverse effects.", "contents": "Pharmacologic therapy of asthma. Asthma is treated by avoiding the precipitants of symptoms, by a trial of hyposensitization (immunotherapy) if the precipitant cannot be avoided, and principally by pharmacologic therapy. Acute attacks have been most widely treated with epinephrine, but adrenergic aerosol bronchodilators and aminophylline are being used increasingly. When an acute attack of asthma does not respond to treatment, a diagnosis of status asthmaticus should be considered and the patient treated in a hospital intensive care unit because of the potentially life-threatening sequela of respiratory failure. Periodic mild episodes of asthma usually respond to administration of an oral bronchodilator. Chronic low-grade asthma is best treated with an around-the-clock regimen of theophylline. Patients whose asthma is not under satisfactory control with conventional bronchodilators may be given a trial of cromolyn sodium. Chronic severe cases may be treated with corticosteroids, but these drugs must be skillfully administered to avoid adverse effects."}
{"id": "PMID:4781", "title": "Managing acute urticaria.", "content": "The physician should be familiar with preventive measures for acute urticaria or its most severe form, anaphylaxis, and with the general principles of management. Treatment does not differ basically whether given in a nonmedical setting, the emergency room, or the office, except for the availability of special supplies and equipment, such as oxygen, if needed. In all cases, a history should be obtained quickly, the patient should be examined to confirm the diagnosis, and epinephrine should be administered. Hospitalization is indicated in severe cases with systemic symptoms. Once the acute episode has been treated, the physician must decide whether further investigation is necessary. Quite often a presumptive etiologic diagnosis is made on the basis of the history. Allergy testing is not part of the routine evaluation of the patient with urticaria.", "contents": "Managing acute urticaria. The physician should be familiar with preventive measures for acute urticaria or its most severe form, anaphylaxis, and with the general principles of management. Treatment does not differ basically whether given in a nonmedical setting, the emergency room, or the office, except for the availability of special supplies and equipment, such as oxygen, if needed. In all cases, a history should be obtained quickly, the patient should be examined to confirm the diagnosis, and epinephrine should be administered. Hospitalization is indicated in severe cases with systemic symptoms. Once the acute episode has been treated, the physician must decide whether further investigation is necessary. Quite often a presumptive etiologic diagnosis is made on the basis of the history. Allergy testing is not part of the routine evaluation of the patient with urticaria."}
{"id": "PMID:4782", "title": "Myocardial ischemia from coronary arterial spasm.", "content": "Spasm of coronary arteries can cause chest pain indistinguishable from classic angina pectoris in patients without atherosclerosis of these vessels or recognizable heart disease. Associated electrocardiographic changes usually correspond to the coronary artery affected and disappear when the attack of pain ends. Sublingual nitrates are excellent agents for the control of the episodic anginal symptoms. There have been scattered reports of myocardial infarction occurring in patients with normal coronary arteries; a role of arterial spasm in these cases in speculative.", "contents": "Myocardial ischemia from coronary arterial spasm. Spasm of coronary arteries can cause chest pain indistinguishable from classic angina pectoris in patients without atherosclerosis of these vessels or recognizable heart disease. Associated electrocardiographic changes usually correspond to the coronary artery affected and disappear when the attack of pain ends. Sublingual nitrates are excellent agents for the control of the episodic anginal symptoms. There have been scattered reports of myocardial infarction occurring in patients with normal coronary arteries; a role of arterial spasm in these cases in speculative."}
{"id": "PMID:4777", "title": "Preparation of drugs used in hyperacidity. Part I. Effects of pH of precipitation on the neutralizing properties of alumina gels.", "content": "Alumina gels were obtained from sodium aluminate by addition of 3 N HNO3, HCl or H2SO4 solutions or by saturation with gaseous CO2. The effect of several physicochemical factors (pH of precipitation, kind and concentration of precipitating agent, temperature) on the neutralizing properties of the obtained forms of Al(OH)3 was investigated. The linear correlation between the pH of precipitation and the neutralizing properties was found. The effect of different precipitating anions on the acid-consuming capacity and the rate of neutralization of 0-1 N HCl was established.", "contents": "Preparation of drugs used in hyperacidity. Part I. Effects of pH of precipitation on the neutralizing properties of alumina gels. Alumina gels were obtained from sodium aluminate by addition of 3 N HNO3, HCl or H2SO4 solutions or by saturation with gaseous CO2. The effect of several physicochemical factors (pH of precipitation, kind and concentration of precipitating agent, temperature) on the neutralizing properties of the obtained forms of Al(OH)3 was investigated. The linear correlation between the pH of precipitation and the neutralizing properties was found. The effect of different precipitating anions on the acid-consuming capacity and the rate of neutralization of 0-1 N HCl was established."}
{"id": "PMID:4778", "title": "Nephron function in acute glycerol-induced renal insufficiency in rabbits.", "content": "The effect of acute experimentally induced renal failure after intramuscular injection of glycerol on serum and urine GGTP, LAP and AP activities was studied in 30 rabbits. High doses of glycerol caused shock, myolysis and hemolysis, leading to acute renal insufficiency. Serum urea and creatinine levels significantly increased, there was proteinuria, and significant decrease in 24-hr diuresis, glomerular filtration, and urinary urea excretion. The changes in LAP and AP activities were significant, and in GGTP-nonsignificant. In the urine GGTP and LAP increased significantly, and AP nonsignificantly. Urinary excretion of AP increased significantly, and GGTP and LAP nonsignificantly. The highest activity and urinary excretion of GGTP and LAP were observed on the 2nd day, and of AP--on the 5th day of renal failure.", "contents": "Nephron function in acute glycerol-induced renal insufficiency in rabbits. The effect of acute experimentally induced renal failure after intramuscular injection of glycerol on serum and urine GGTP, LAP and AP activities was studied in 30 rabbits. High doses of glycerol caused shock, myolysis and hemolysis, leading to acute renal insufficiency. Serum urea and creatinine levels significantly increased, there was proteinuria, and significant decrease in 24-hr diuresis, glomerular filtration, and urinary urea excretion. The changes in LAP and AP activities were significant, and in GGTP-nonsignificant. In the urine GGTP and LAP increased significantly, and AP nonsignificantly. Urinary excretion of AP increased significantly, and GGTP and LAP nonsignificantly. The highest activity and urinary excretion of GGTP and LAP were observed on the 2nd day, and of AP--on the 5th day of renal failure."}
{"id": "PMID:4783", "title": "Angina pectoris. Diagnosis and treatment.", "content": "The physician who understands the pathophysiology of angina pectoris can apply rational therapeutic measures based on an appreciation of the determinants of myocardial oxygen supply and demand. Most patients with angina secondary to coronary atherosclerosis can be treated conservatively using a systematic approach that includes correction or removal of underlying causes or precipitating factors and the judicious use of sublingual nitroglycerin. In patients with more resistant angina, use of oral or topical nitroglycerin or sublingual isosorbide dinitrite as well as propranolol can be advised. Aortocoronary bypass surgery can offer significant improvement in carefully selected patients with frequent angina poorly controlled by medical therapy. The most important consideration in the treatment of angina is protection of coronary blood flow reserve by primary prevention of the atherosclerotic process itself. All individuals from families prone to coronary artery disease should be evaluated for alterable risk factors, the most important being cigarette smoking, hypertension, and hypercholesterolemia. Considering the high risk of unheralded sudden death in previously asymptomatic patients with coronary atherosclerosis, angina can, in a sense, be considered a fortunate harbinger of coronary stenosis, identifying candidates for secondary preventive measures aimed at retarding the progression of vascular disease. More importantly, angina serves as an index for detecting families at high risk of coronary artery disease, in whom early application of primary prevention may afford a more promising outlook.", "contents": "Angina pectoris. Diagnosis and treatment. The physician who understands the pathophysiology of angina pectoris can apply rational therapeutic measures based on an appreciation of the determinants of myocardial oxygen supply and demand. Most patients with angina secondary to coronary atherosclerosis can be treated conservatively using a systematic approach that includes correction or removal of underlying causes or precipitating factors and the judicious use of sublingual nitroglycerin. In patients with more resistant angina, use of oral or topical nitroglycerin or sublingual isosorbide dinitrite as well as propranolol can be advised. Aortocoronary bypass surgery can offer significant improvement in carefully selected patients with frequent angina poorly controlled by medical therapy. The most important consideration in the treatment of angina is protection of coronary blood flow reserve by primary prevention of the atherosclerotic process itself. All individuals from families prone to coronary artery disease should be evaluated for alterable risk factors, the most important being cigarette smoking, hypertension, and hypercholesterolemia. Considering the high risk of unheralded sudden death in previously asymptomatic patients with coronary atherosclerosis, angina can, in a sense, be considered a fortunate harbinger of coronary stenosis, identifying candidates for secondary preventive measures aimed at retarding the progression of vascular disease. More importantly, angina serves as an index for detecting families at high risk of coronary artery disease, in whom early application of primary prevention may afford a more promising outlook."}
{"id": "PMID:4785", "title": "Intranasal beclomethasone dipropionate in seasonal rhinitis in general practice.", "content": "Thirty-five patients with seasonal allergic rhinitis were treated in a double-blind comparative trial in and East London Group Practice with either beclomethasone dipropionate (50 micrograms in each nostril four times a day) or a placebo aerosol preparation identical in appearance. There was a statistically significant difference in favour of intranasal beclomethasone dipropionate (P less than 0-05).", "contents": "Intranasal beclomethasone dipropionate in seasonal rhinitis in general practice. Thirty-five patients with seasonal allergic rhinitis were treated in a double-blind comparative trial in and East London Group Practice with either beclomethasone dipropionate (50 micrograms in each nostril four times a day) or a placebo aerosol preparation identical in appearance. There was a statistically significant difference in favour of intranasal beclomethasone dipropionate (P less than 0-05)."}
{"id": "PMID:4786", "title": "[Cerebral palsy--early diagnosis and treatment (author's transl)].", "content": "The main aim of the present Conference has been to debate that early diagnosis and treatment of cerebral palsy. The Conference was attended by specialists taking care of the child with cerebral palsy (C.P.): child neurologists, surgeons--orthopedists, psychologists, rehabilitants, pediatricians. In connection with the fact that the Conference was devoted to the early diagnosis and therapy of C.P., problems concerning the lower age groups of children were debated. The Conference discussed the definitions of \"cerebral palsy\" used in the literature, the clinical forms, the auxiliary diagnostic methods and their significance in the diagnosing of this pathological syndrome. Early clinical symptoms, enabling to establish the diagnosis of cerebral palsy were particularly extensively debated. In the latter problem particular attention was paid to the diagnostic value of kinetic automatisms of the group of tonic posture reflexes and dysfunctions of the kinetic pattern in children. It was underlined in the debate the C.P. was no separate clinical disease, but a pathological syndrome arisen as a result of the negative influence of different factors and yielding very diverse clinical and neurolopathologic symptoms, according to the kind of noxious factors and the period and degree of maturity of the nervous system in which they acted. The participants in the debate also sressed that, as the child develops and is observed for a longer period it is fairly often necessary to check this diagnosis, as C.P. may prove, as the time passes, to be a degenerative syndrome, a pressure syndrome etc. The psychologists participating in the Conference discussed the psychological problems of the child with C.P. and also the early diagnosis of the pathological syndrome debated. The diversity of the symptoms of the C.N.S. in children suffering from C.P. was underscored, as--apart from dysfunctions within the kinetic area, there can be present sight, hearing and speech dysfunctions, those of sensory perceptions and mental development. These children require multispecialist care, as everyone of dysfunctions mentioned may present a complicated diagnostic problem. Plenty of place was devoted to the discussion of problems connected with epilepsy in children with C.P. Also extensively debated were the general principles of the medical procedure in children with C.P. As a result of the discussion it was decided that children with severer forms of C.P. and those from poor social conditions should be subjected to long-lasting sanatorium rehabilitation. Keeping the child in its family environment should, however, be the generally adopted principle of the rehabilitation of a little child. The parents of the child should be trained in the proper rearing of the child under household conditions, a manner to secure all the needs resulting from the then stage of its development. In connection with this problem the project of the programme of sensoric-and-kinetic rehabilitation was debated, as presented by psychologists and rehabilitants (kinesitherapeuts).", "contents": "[Cerebral palsy--early diagnosis and treatment (author's transl)]. The main aim of the present Conference has been to debate that early diagnosis and treatment of cerebral palsy. The Conference was attended by specialists taking care of the child with cerebral palsy (C.P.): child neurologists, surgeons--orthopedists, psychologists, rehabilitants, pediatricians. In connection with the fact that the Conference was devoted to the early diagnosis and therapy of C.P., problems concerning the lower age groups of children were debated. The Conference discussed the definitions of \"cerebral palsy\" used in the literature, the clinical forms, the auxiliary diagnostic methods and their significance in the diagnosing of this pathological syndrome. Early clinical symptoms, enabling to establish the diagnosis of cerebral palsy were particularly extensively debated. In the latter problem particular attention was paid to the diagnostic value of kinetic automatisms of the group of tonic posture reflexes and dysfunctions of the kinetic pattern in children. It was underlined in the debate the C.P. was no separate clinical disease, but a pathological syndrome arisen as a result of the negative influence of different factors and yielding very diverse clinical and neurolopathologic symptoms, according to the kind of noxious factors and the period and degree of maturity of the nervous system in which they acted. The participants in the debate also sressed that, as the child develops and is observed for a longer period it is fairly often necessary to check this diagnosis, as C.P. may prove, as the time passes, to be a degenerative syndrome, a pressure syndrome etc. The psychologists participating in the Conference discussed the psychological problems of the child with C.P. and also the early diagnosis of the pathological syndrome debated. The diversity of the symptoms of the C.N.S. in children suffering from C.P. was underscored, as--apart from dysfunctions within the kinetic area, there can be present sight, hearing and speech dysfunctions, those of sensory perceptions and mental development. These children require multispecialist care, as everyone of dysfunctions mentioned may present a complicated diagnostic problem. Plenty of place was devoted to the discussion of problems connected with epilepsy in children with C.P. Also extensively debated were the general principles of the medical procedure in children with C.P. As a result of the discussion it was decided that children with severer forms of C.P. and those from poor social conditions should be subjected to long-lasting sanatorium rehabilitation. Keeping the child in its family environment should, however, be the generally adopted principle of the rehabilitation of a little child. The parents of the child should be trained in the proper rearing of the child under household conditions, a manner to secure all the needs resulting from the then stage of its development. In connection with this problem the project of the programme of sensoric-and-kinetic rehabilitation was debated, as presented by psychologists and rehabilitants (kinesitherapeuts)."}
{"id": "PMID:4787", "title": "[Congenital heart malformations in neonates, infants and young children (author's transl)].", "content": "Congenital heart malformations in neonates, infants and young children represent the main problem of paediatric cardiology in Poland. Congenital cardiovascular diseases (incidence also approximately 8 per 1000 in liveborn infants) cause very high mortality, particularly in the neonatal and infantile period. Approximately 5000 live-born children are affected every year by serious heart malformations. For at least two thirds of these previously hopelessly ill infants there are real possibilities of effective medical and surgical treatment. Not only a considerable drop in mortality in the earliest infancy would be achieved, but: a further normal physical and psychical growth and development of these children would be possible. At present, however, the available possibilities are by far not sufficient, as in all hitherto functioning centres we were able to manage 200-300 children yearly, whereas the real needs are at leasttenfold greater. Therefore it is necessary to: Increase the number and capacity of hospital wards capable enough to provide the intensive cardiopulmonary care; to execute appropriate reorganization aimed to concentrating the appropriate specialists (pediatric cardiologists, radiologists, surgeons, anesthesiologists, nurses) and equipment (cardiological and cardiosurgical appliances, X-ray equipment, intensive care units etc.) in centres designated for the above tasks. At least 7 paediatric intensive care and cardiosurgical centres should be instituted in Poland for a satisfactory management of congenital heart diseases.", "contents": "[Congenital heart malformations in neonates, infants and young children (author's transl)]. Congenital heart malformations in neonates, infants and young children represent the main problem of paediatric cardiology in Poland. Congenital cardiovascular diseases (incidence also approximately 8 per 1000 in liveborn infants) cause very high mortality, particularly in the neonatal and infantile period. Approximately 5000 live-born children are affected every year by serious heart malformations. For at least two thirds of these previously hopelessly ill infants there are real possibilities of effective medical and surgical treatment. Not only a considerable drop in mortality in the earliest infancy would be achieved, but: a further normal physical and psychical growth and development of these children would be possible. At present, however, the available possibilities are by far not sufficient, as in all hitherto functioning centres we were able to manage 200-300 children yearly, whereas the real needs are at leasttenfold greater. Therefore it is necessary to: Increase the number and capacity of hospital wards capable enough to provide the intensive cardiopulmonary care; to execute appropriate reorganization aimed to concentrating the appropriate specialists (pediatric cardiologists, radiologists, surgeons, anesthesiologists, nurses) and equipment (cardiological and cardiosurgical appliances, X-ray equipment, intensive care units etc.) in centres designated for the above tasks. At least 7 paediatric intensive care and cardiosurgical centres should be instituted in Poland for a satisfactory management of congenital heart diseases."}
{"id": "PMID:4788", "title": "[Ribonuclease activity in the serum of children of various ages (author's transl)].", "content": "The normal levels of ribonuclease activity in the serum of children of both sexes of various ages. The children into four age groups: thee 1st grous--from 1 to 7 days of age, the 2nd--from 1 to 12 months, 3rd--from 1 to 3 years, 4th--from 7 to 14 years of age. The ribonuclease activity amounted, in the various age groups, respectively tto: 1st group--0.27+0.07 ug/ml of serum, 2nd--0.21+0.06 ug/ml, 3rd--0.15+0.04 ug/ml, 4th--0.14+0.04 ug/ml.", "contents": "[Ribonuclease activity in the serum of children of various ages (author's transl)]. The normal levels of ribonuclease activity in the serum of children of both sexes of various ages. The children into four age groups: thee 1st grous--from 1 to 7 days of age, the 2nd--from 1 to 12 months, 3rd--from 1 to 3 years, 4th--from 7 to 14 years of age. The ribonuclease activity amounted, in the various age groups, respectively tto: 1st group--0.27+0.07 ug/ml of serum, 2nd--0.21+0.06 ug/ml, 3rd--0.15+0.04 ug/ml, 4th--0.14+0.04 ug/ml."}
{"id": "PMID:4793", "title": "Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase.", "content": "The tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally). This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr. A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats.", "contents": "Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. The tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally). This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr. A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection. Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats."}
{"id": "PMID:4794", "title": "A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney.", "content": "Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme. In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway.", "contents": "A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney. Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme. In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway."}
{"id": "PMID:4795", "title": "Specific positions involved in enzyme catalyzed covalent binding of benzo[a]pyrene to poly(G).", "content": "Covalent binding of benzo[a]pyrene to poly(G) was studied with the use of a radioactive assay and specifically labeled substrates to define the role of the 1, 3- and 6-positions of the hydrocarbon during this process. Binding was shown to be dependent on microsomes, NADPH, O2 and poly(G). 7, 8-Benzoflavone and 2', 2'-diethylaminoethyl-2, 2-diphenyl valerate were inhibitory w.hereas modulators of epoxide hydrase activity had little effect. 3H and 14C studies suggested a possible loss of one to two protons. Incorporation of [6-3H1]benzo[a]pyrene provided evidence that the 6-position of the hydrocarbon was not metabolized during covalent attachment to poly(G) and, furthermore, results with [1, 3, 6-3H]benzo[a]pyrene suggest that the 1- and 3-positions may not be involved either. After scaling up of the standard assay 20-fold, characterization of the tritiated BaP-poly(G) complex was carried out by hydrolysis and subsequent chromatography. Thin-layer chromatography of the isolated hydrolysis products treated with HCl or alkaline phosphatase indicated that the complex formed between BaP and poly(G) was covalently linked and composed of hydrocarbon-nucleotide(s).", "contents": "Specific positions involved in enzyme catalyzed covalent binding of benzo[a]pyrene to poly(G). Covalent binding of benzo[a]pyrene to poly(G) was studied with the use of a radioactive assay and specifically labeled substrates to define the role of the 1, 3- and 6-positions of the hydrocarbon during this process. Binding was shown to be dependent on microsomes, NADPH, O2 and poly(G). 7, 8-Benzoflavone and 2', 2'-diethylaminoethyl-2, 2-diphenyl valerate were inhibitory w.hereas modulators of epoxide hydrase activity had little effect. 3H and 14C studies suggested a possible loss of one to two protons. Incorporation of [6-3H1]benzo[a]pyrene provided evidence that the 6-position of the hydrocarbon was not metabolized during covalent attachment to poly(G) and, furthermore, results with [1, 3, 6-3H]benzo[a]pyrene suggest that the 1- and 3-positions may not be involved either. After scaling up of the standard assay 20-fold, characterization of the tritiated BaP-poly(G) complex was carried out by hydrolysis and subsequent chromatography. Thin-layer chromatography of the isolated hydrolysis products treated with HCl or alkaline phosphatase indicated that the complex formed between BaP and poly(G) was covalently linked and composed of hydrocarbon-nucleotide(s)."}
{"id": "PMID:4796", "title": "Simple model for hormone-activated adenylate cyclase systems.", "content": "A simple model is developed to explain the activation of rat liver plasma membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by guanosine nucleotides and glucagon and the dependence of the cATALYTIC RATE ON Mg2+, H+, and substrate concentrations. The basic model proposes that the adenylate cyclase system can exist in two states, A and B; that activating ligands bind preferentially to the B state; and that only the B state is active. Kinetic data are quantitatively fit to this model, and the binding constants for the interaction of the A and B states with glucagon, GTP, and guanyl-5'-ylimidodiphosphate are obtinaed. The substrates ATP and adenyl-5'-ylimidodiphosphate appear to show little preference between the A and B states, and simple Michaelis-Menten kinetics are sufficient to describe the dependence of the catalytic rate on substrate concentration under optimal conditions. The dependence of the rate on pH can be explained by postulating that one ionizable group in its acid form and one ionizable group in its basic form must be present at the active site in order for catalysis to occur. The activation and inhibition of the activity by Mg2+ can be explained by a similar mechanism with Mg2+ binding to activating and inhibiting sites. Glucagon and guanosine nucleotides appear to influence the dependence of the rate on Mg2+ and glucagon. The Mg2+ also may display some preference for the B state. A comparison of this model with others that have been proposed is given. The proposed model appears to provide a simple conceptual frame-work that is applicable to many adenylate cyclase systems.", "contents": "Simple model for hormone-activated adenylate cyclase systems. A simple model is developed to explain the activation of rat liver plasma membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by guanosine nucleotides and glucagon and the dependence of the cATALYTIC RATE ON Mg2+, H+, and substrate concentrations. The basic model proposes that the adenylate cyclase system can exist in two states, A and B; that activating ligands bind preferentially to the B state; and that only the B state is active. Kinetic data are quantitatively fit to this model, and the binding constants for the interaction of the A and B states with glucagon, GTP, and guanyl-5'-ylimidodiphosphate are obtinaed. The substrates ATP and adenyl-5'-ylimidodiphosphate appear to show little preference between the A and B states, and simple Michaelis-Menten kinetics are sufficient to describe the dependence of the catalytic rate on substrate concentration under optimal conditions. The dependence of the rate on pH can be explained by postulating that one ionizable group in its acid form and one ionizable group in its basic form must be present at the active site in order for catalysis to occur. The activation and inhibition of the activity by Mg2+ can be explained by a similar mechanism with Mg2+ binding to activating and inhibiting sites. Glucagon and guanosine nucleotides appear to influence the dependence of the rate on Mg2+ and glucagon. The Mg2+ also may display some preference for the B state. A comparison of this model with others that have been proposed is given. The proposed model appears to provide a simple conceptual frame-work that is applicable to many adenylate cyclase systems."}
{"id": "PMID:4797", "title": "Heat mutagenesis in bacteriophage T4: the transition pathway.", "content": "G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis. Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation.", "contents": "Heat mutagenesis in bacteriophage T4: the transition pathway. G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis. Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation."}
{"id": "PMID:4798", "title": "beta-adrenergic receptors in rat liver: effects of adrenalectomy.", "content": "The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist. Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors. The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone. The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy.", "contents": "beta-adrenergic receptors in rat liver: effects of adrenalectomy. The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist. Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors. The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone. The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy."}
{"id": "PMID:4799", "title": "Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin.", "content": "Solubilities of deoxygenated sickle cell hemoglobin (deoxy-Hb S), at varying pH and temperature over a range of concentrations encompassing those found in erythrocytes, were measured. The technique involved ultracentrifugation, which gave values of the supernatant concentration and the mass of the sedimented material. The data establish that the solubility of doexy-Hb S is the saturation concentration and is independent of initial concentration. The mass of the pellet phase increases linearly with initial concentration. Moreover, the saturation concentration represents the critical concentration above which monomers are in equilibrium with polymers. These polymers are the putative cause of erythrocytes deformation associated with sickle cell anemia. The solubility-pH profiles of deoxy-Hb S at various temperatures, unlike those of other proteins, show no minima at the isoelectric pH but instead show a marked decrease in solubility below pH 7.0, indicating the predominance of polymerization over the expected increase in solubility. Deoxy-Hb S, within specified ranges of temperature and pH, possesses a negative temperature coefficient of solubility, a property characteristic of hydrophobic interactions. The saturation concentration is, however, temperature independent at conditions close to physiological. The enthalpy of polymerization (3.5 kcal/mol) is temperature independent from 6 degrees to 22 degrees for all pH values between 6.45 and 7.40. In the range of 22 degrees to 38 degrees, this parameter becomes less endothermic, having a value of 2.5 kcal/mol at pH 6.45 and a value of zero at pH 7.20. Such behavior of the system suggests a phase transition near 22 degreas. Within the range of conditions examined the polymerization is entropically driven.", "contents": "Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin. Solubilities of deoxygenated sickle cell hemoglobin (deoxy-Hb S), at varying pH and temperature over a range of concentrations encompassing those found in erythrocytes, were measured. The technique involved ultracentrifugation, which gave values of the supernatant concentration and the mass of the sedimented material. The data establish that the solubility of doexy-Hb S is the saturation concentration and is independent of initial concentration. The mass of the pellet phase increases linearly with initial concentration. Moreover, the saturation concentration represents the critical concentration above which monomers are in equilibrium with polymers. These polymers are the putative cause of erythrocytes deformation associated with sickle cell anemia. The solubility-pH profiles of deoxy-Hb S at various temperatures, unlike those of other proteins, show no minima at the isoelectric pH but instead show a marked decrease in solubility below pH 7.0, indicating the predominance of polymerization over the expected increase in solubility. Deoxy-Hb S, within specified ranges of temperature and pH, possesses a negative temperature coefficient of solubility, a property characteristic of hydrophobic interactions. The saturation concentration is, however, temperature independent at conditions close to physiological. The enthalpy of polymerization (3.5 kcal/mol) is temperature independent from 6 degrees to 22 degrees for all pH values between 6.45 and 7.40. In the range of 22 degrees to 38 degrees, this parameter becomes less endothermic, having a value of 2.5 kcal/mol at pH 6.45 and a value of zero at pH 7.20. Such behavior of the system suggests a phase transition near 22 degreas. Within the range of conditions examined the polymerization is entropically driven."}
{"id": "PMID:4812", "title": "Difference in the number of insulin binding sites between cortisol-sensitive and cortisol-resistant lymphoma P1798 cells.", "content": "Cortisol-sensitive and cortisol-resistant lymphoma P1798 cells specifically bind [25I]insulin. Resistant lymphocytes bind 40% less insulin than sensitive cells. These results suggest that insulin (or insulin-like substances) may play a role in growth regulation and/or response of this tumor to glucocorticoid therapy.", "contents": "Difference in the number of insulin binding sites between cortisol-sensitive and cortisol-resistant lymphoma P1798 cells. Cortisol-sensitive and cortisol-resistant lymphoma P1798 cells specifically bind [25I]insulin. Resistant lymphocytes bind 40% less insulin than sensitive cells. These results suggest that insulin (or insulin-like substances) may play a role in growth regulation and/or response of this tumor to glucocorticoid therapy."}
{"id": "PMID:4813", "title": "Action of histamine and its receptor blockers on uterine circulation in sheep.", "content": "Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes. Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors. The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide.", "contents": "Action of histamine and its receptor blockers on uterine circulation in sheep. Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes. Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors. The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide."}
{"id": "PMID:4814", "title": "Alpha-MSH and MIF-2 effects on serotonin levels and accumulation in various rat brain areas.", "content": "Levels as well as accumulation of serotonin (5-HT) were measured in various brain regions of the rat after administration of alpha-melanocyte-stimulating hormone (MSH) and Pro-Leu-Gly-NH2 (MIF-I). The method used in determining the serotonin measured both 5-OH-tryptamine (5-HT) and 5-methoxytryptamine (5-MT). No statistically significant changes in levels or accumulation of serotonin after pargyline injection were found when unoperated control rats were treated with either MSH or MIF-I. Similar treatment of hypophysectomized rats indicated that both peptides significantly (p less than 0.05) lowered serotonin accumulation only in the area of the frontal cortex; a similar but smaller, not statistically significant, decrease was seen in the hypothalamus and hippocampus of the hypophysectomized rat. Since only hypophysectomized rats were affected, no correlation between the behavioral effects of these peptides (which has been found to occur in both unoperated and hypophysectomized rats) and the biochemical changes could be made.", "contents": "Alpha-MSH and MIF-2 effects on serotonin levels and accumulation in various rat brain areas. Levels as well as accumulation of serotonin (5-HT) were measured in various brain regions of the rat after administration of alpha-melanocyte-stimulating hormone (MSH) and Pro-Leu-Gly-NH2 (MIF-I). The method used in determining the serotonin measured both 5-OH-tryptamine (5-HT) and 5-methoxytryptamine (5-MT). No statistically significant changes in levels or accumulation of serotonin after pargyline injection were found when unoperated control rats were treated with either MSH or MIF-I. Similar treatment of hypophysectomized rats indicated that both peptides significantly (p less than 0.05) lowered serotonin accumulation only in the area of the frontal cortex; a similar but smaller, not statistically significant, decrease was seen in the hypothalamus and hippocampus of the hypophysectomized rat. Since only hypophysectomized rats were affected, no correlation between the behavioral effects of these peptides (which has been found to occur in both unoperated and hypophysectomized rats) and the biochemical changes could be made."}
{"id": "PMID:4815", "title": "Alpha-MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas.", "content": "Attempts were made to find a biochemical correlate with previously observed behavioral alterations after administration of alpha-melanocyte-stimulating hormone (MSH) and MSH release-inhibiting factor (MIF-I). Brains of intact and hypophysectomized (hypox) rats were analyzed for endogenous catecholamine levels and the disappearance rate of endogenous norepinephrine (NE) after treatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). The studies undertaken show the following: (1) After the injection of MSH (100 mug/kg IP daily x 3) and AMPT, samples in different groups of intact and hypox rats were taken at 0, 1, 2, 4 and 6 hrs in 7 different brain areas. In the mid-brain area for the intact group of rats, the rate of disappearance of NE was faster and for the hypox rats it was slower than the rate for control rats not treated with the peptides. NE levels in the same area at time 0 were 11 percent lower than controls in hypox rats and unchanged in unoperated animals. (2) After the injection of MIF-I (20 mg/kg IP daily x 3) in similar experiments as with MSH, a reduced rate (p less than 0.05) of NE disappearance for the first 4 hr and an increased rate (p less than 0.05) of NE disappearance for the last 2 hr of the experiments occurred for both the intact and hypox rats in the mid-brain area where endogenous NE levels were lowered by 11 and 12 percent at 0 min. In no other brain areas were alterations in NE breakdown found in both the intact and hypox rat groups. Behavioral changes have been found previously under similar experimental conditions in both intact and hypox rats. (3) Rates of dopamine disappearance in experiments similar to those described for NE disappearance indicated that in the striatal brain area no change was found in the intact rats after either MSH or MIF-I, whereas a decrease in DA disappearance was found for hypox rats during the six hour experimental period only after MSH. The results indicate that a correlation between behavioral changes, rates of disappearance and endogenous levels of NE in the mid-brain area may occur after MIF-I at the times examined but that a similar correlation for MSH did not appear likely.", "contents": "Alpha-MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas. Attempts were made to find a biochemical correlate with previously observed behavioral alterations after administration of alpha-melanocyte-stimulating hormone (MSH) and MSH release-inhibiting factor (MIF-I). Brains of intact and hypophysectomized (hypox) rats were analyzed for endogenous catecholamine levels and the disappearance rate of endogenous norepinephrine (NE) after treatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). The studies undertaken show the following: (1) After the injection of MSH (100 mug/kg IP daily x 3) and AMPT, samples in different groups of intact and hypox rats were taken at 0, 1, 2, 4 and 6 hrs in 7 different brain areas. In the mid-brain area for the intact group of rats, the rate of disappearance of NE was faster and for the hypox rats it was slower than the rate for control rats not treated with the peptides. NE levels in the same area at time 0 were 11 percent lower than controls in hypox rats and unchanged in unoperated animals. (2) After the injection of MIF-I (20 mg/kg IP daily x 3) in similar experiments as with MSH, a reduced rate (p less than 0.05) of NE disappearance for the first 4 hr and an increased rate (p less than 0.05) of NE disappearance for the last 2 hr of the experiments occurred for both the intact and hypox rats in the mid-brain area where endogenous NE levels were lowered by 11 and 12 percent at 0 min. In no other brain areas were alterations in NE breakdown found in both the intact and hypox rat groups. Behavioral changes have been found previously under similar experimental conditions in both intact and hypox rats. (3) Rates of dopamine disappearance in experiments similar to those described for NE disappearance indicated that in the striatal brain area no change was found in the intact rats after either MSH or MIF-I, whereas a decrease in DA disappearance was found for hypox rats during the six hour experimental period only after MSH. The results indicate that a correlation between behavioral changes, rates of disappearance and endogenous levels of NE in the mid-brain area may occur after MIF-I at the times examined but that a similar correlation for MSH did not appear likely."}
{"id": "PMID:4818", "title": "Self-administration of psychomotor stimulant drugs: the effects of unlimited access.", "content": "Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.", "contents": "Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake."}
{"id": "PMID:4819", "title": "Rate-dependent effects of drugs: a review of the literature.", "content": "It has been claimed that the effects of amphetamines on schedule-controlled behavior depend to a large extent on the rate of responding in control conditions. A review of the literature shows that there is considerable support for this hypothesis if the behavior is not suppressed by aversive procedures, is not under the control of powerful external stimuli or is not occurring very infrequently. The extension of a rate-dependency hypothesis to the effects of other drugs has less empirical support, however. It is argued that many of the procedures used for studying rate-dependent drug effects do not provide critical tests of the hypothesis. If it is to be shown unequivocally that it is rate of operant responding which determines the behavioral effects of drugs, procedures are needed in which other varibles such as reinforcement frequency are more adequately controlled.", "contents": "Rate-dependent effects of drugs: a review of the literature. It has been claimed that the effects of amphetamines on schedule-controlled behavior depend to a large extent on the rate of responding in control conditions. A review of the literature shows that there is considerable support for this hypothesis if the behavior is not suppressed by aversive procedures, is not under the control of powerful external stimuli or is not occurring very infrequently. The extension of a rate-dependency hypothesis to the effects of other drugs has less empirical support, however. It is argued that many of the procedures used for studying rate-dependent drug effects do not provide critical tests of the hypothesis. If it is to be shown unequivocally that it is rate of operant responding which determines the behavioral effects of drugs, procedures are needed in which other varibles such as reinforcement frequency are more adequately controlled."}
{"id": "PMID:4816", "title": "Effect of various 6-hydroxydopamine treatments during development on growth and ingestive behavior.", "content": "Destruction of catecholamine-containing fibers in brain at 5 days of age with intracisternal injection of 6-hydroxydopamine reduced body growth, intake of a sucrose solution, and acquisition of an active avoidance response. Further characterization of behavioral deficits indicated that treated animals also showed reduced ingestion of saline solution when injected with desoxycorticosterone and a decreased eating response to insulin. In addition, all of these deficits produced by catecholamine depletion with 6-hydroxydopamine were observed in rats in which brain dopamine was preferentially reduced but not in rats having preferential destruction of noradrenergic fibers, suggesting that dopamine depletion amounts for the observed alterations in developing animals. Although animals treated with 6-hydroxydopamine at 14 days showed reduced intake of a sucrose solution, they did not have reduced growth. Since early malnourishment reduced growth, it seems possible that the reduced growth observed after destruction of dopaminergeic fibers may be related to an acute reduction of food intake which is perpetuated by persistent deficits in ingestive behavior. Evidence implicating malnourishment in other deficits produced by 6-hydroxydopamine could not be obtained.", "contents": "Effect of various 6-hydroxydopamine treatments during development on growth and ingestive behavior. Destruction of catecholamine-containing fibers in brain at 5 days of age with intracisternal injection of 6-hydroxydopamine reduced body growth, intake of a sucrose solution, and acquisition of an active avoidance response. Further characterization of behavioral deficits indicated that treated animals also showed reduced ingestion of saline solution when injected with desoxycorticosterone and a decreased eating response to insulin. In addition, all of these deficits produced by catecholamine depletion with 6-hydroxydopamine were observed in rats in which brain dopamine was preferentially reduced but not in rats having preferential destruction of noradrenergic fibers, suggesting that dopamine depletion amounts for the observed alterations in developing animals. Although animals treated with 6-hydroxydopamine at 14 days showed reduced intake of a sucrose solution, they did not have reduced growth. Since early malnourishment reduced growth, it seems possible that the reduced growth observed after destruction of dopaminergeic fibers may be related to an acute reduction of food intake which is perpetuated by persistent deficits in ingestive behavior. Evidence implicating malnourishment in other deficits produced by 6-hydroxydopamine could not be obtained."}
{"id": "PMID:4820", "title": "Schedule-induced oral self administration of etonitazene.", "content": "Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water. When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution.", "contents": "Schedule-induced oral self administration of etonitazene. Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water. When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution."}
{"id": "PMID:4817", "title": "Enzyme activity in sleep and sleep deprivation.", "content": "Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night. That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats. However, in these rats the enzyme activity did not become low in the sleep-deprived-sleeping condition. Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis.", "contents": "Enzyme activity in sleep and sleep deprivation. Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night. That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats. However, in these rats the enzyme activity did not become low in the sleep-deprived-sleeping condition. Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis."}
{"id": "PMID:4830", "title": "The genetics of the mimetic butterfly Hypolimnas bolina (L.).", "content": "Hypolimnas bolina is a Nymphalid butterfly having a west to east distribution from Madagascar to Easter Island, and a north to south one from Japan to Australasia. It is highly migratory in some areas. In much of the western part of its range the female is both monomorphic and a mimic of Euploea. Further east it is frequently polymorphic with the majority of the forms being non-mimetic. The polymorphism is sex-limited to the female and controlled by two unlinked loci, one with two allelomorphs, E and e, determining the extent of the dark pigmentation, the other with three allelomorphs, P, Pn and p, determining the presence and distribution of orange-brown. Only butterflies of the genotypes EEpp and to a lesser extent Eepp are satisfactory Batesian mimics of their Euploea models. The details of the mimetic pattern are under multifactorial control, following those of their local model, as is much of the variation within the non-mimetic forms, particularly with regard to the distribution of white and blue scaling.", "contents": "The genetics of the mimetic butterfly Hypolimnas bolina (L.). Hypolimnas bolina is a Nymphalid butterfly having a west to east distribution from Madagascar to Easter Island, and a north to south one from Japan to Australasia. It is highly migratory in some areas. In much of the western part of its range the female is both monomorphic and a mimic of Euploea. Further east it is frequently polymorphic with the majority of the forms being non-mimetic. The polymorphism is sex-limited to the female and controlled by two unlinked loci, one with two allelomorphs, E and e, determining the extent of the dark pigmentation, the other with three allelomorphs, P, Pn and p, determining the presence and distribution of orange-brown. Only butterflies of the genotypes EEpp and to a lesser extent Eepp are satisfactory Batesian mimics of their Euploea models. The details of the mimetic pattern are under multifactorial control, following those of their local model, as is much of the variation within the non-mimetic forms, particularly with regard to the distribution of white and blue scaling."}
{"id": "PMID:4831", "title": "Terrestrial vertebrates of the New Hebrides: origin and distribution.", "content": "The known terrestrial vertebrate fauna of the New Hebrides consists of 16 species of mammals (excluding feral domestic stock), 61 species of resident land- and freshwater birds, 20 species of reptiles and one amphibian. Of these, three, five, four and one species respectively have apparently been introduced by man. The non-introduced fauna is clearly Indo-Australian in origin, but some species have an exclusively Pacific island distribution and others (two bats, seven birds, and four lizards) are endemic. On the six islands visited 95 out of the possible 98 vertebrate species occur. Santo, the largest and most northerly island, supports the richest fauna. The comparative impoverishment of more southerly islands is not directly attributable to the progressive increase in isolation and distance from presumptive source area, nor to decrease in island area or maximum height.", "contents": "Terrestrial vertebrates of the New Hebrides: origin and distribution. The known terrestrial vertebrate fauna of the New Hebrides consists of 16 species of mammals (excluding feral domestic stock), 61 species of resident land- and freshwater birds, 20 species of reptiles and one amphibian. Of these, three, five, four and one species respectively have apparently been introduced by man. The non-introduced fauna is clearly Indo-Australian in origin, but some species have an exclusively Pacific island distribution and others (two bats, seven birds, and four lizards) are endemic. On the six islands visited 95 out of the possible 98 vertebrate species occur. Santo, the largest and most northerly island, supports the richest fauna. The comparative impoverishment of more southerly islands is not directly attributable to the progressive increase in isolation and distance from presumptive source area, nor to decrease in island area or maximum height."}
{"id": "PMID:4832", "title": "5-Aminolaevulinic acid dehydratase: structure, function, and mechanism.", "content": "delta-Aminolaevulinic acid dehydratase catalyses the synthesis of porphobilinogen. The enzyme has a molecular mass of 285000 and is composed of eight similar subunits of molecular mass 35000. The N-terminal amino acid is acylated, and the number of peptides found on tryptic digestion equals the number of lysine and arginine residues per mass of 35000. The eight subunits are apparently arranged at the corners of a cube and therefore have dihedral (D4) symmetry. The bovine liver enzyme which has been cystallized contains 4--6 atoms of zinc per mole of enzyme. The apo-enzyme obtained on prolonged hydrolysis can be reactivated by the addition of zinc or cadmium ions. The dialysed enzyme must be first treated with dithiothreitol. There are two very active SH groups in a total of 6--7-SH groups per subunit. The substrate forms a Schiff base with the epsilon-amino group of a lysine residue. Reduction of the Schiff base with NaBH4 should reveal the number of active sites per mole of enzyme. It appears that only four of the eight subunits form a Schiff base with the substrate indicating that the enzyme exhibits the phenomenon of either half-site reactivity or negative cooperativity. The enzyme appears to have a strong subunit-subunit interaction for an immobilized preparation remained stable for at least a month. An immobilized enzyme preparation was treated in a manner so that it dissociated into tetramers. Both the eluate and protein still attached to the Sepharose on a column were enzymically active. The bound enzyme could not reassociate under assay conditions but still contained about 50% of the original enzyme activity. It would seem that the enzyme is active when composed with less than eight subunits.", "contents": "5-Aminolaevulinic acid dehydratase: structure, function, and mechanism. delta-Aminolaevulinic acid dehydratase catalyses the synthesis of porphobilinogen. The enzyme has a molecular mass of 285000 and is composed of eight similar subunits of molecular mass 35000. The N-terminal amino acid is acylated, and the number of peptides found on tryptic digestion equals the number of lysine and arginine residues per mass of 35000. The eight subunits are apparently arranged at the corners of a cube and therefore have dihedral (D4) symmetry. The bovine liver enzyme which has been cystallized contains 4--6 atoms of zinc per mole of enzyme. The apo-enzyme obtained on prolonged hydrolysis can be reactivated by the addition of zinc or cadmium ions. The dialysed enzyme must be first treated with dithiothreitol. There are two very active SH groups in a total of 6--7-SH groups per subunit. The substrate forms a Schiff base with the epsilon-amino group of a lysine residue. Reduction of the Schiff base with NaBH4 should reveal the number of active sites per mole of enzyme. It appears that only four of the eight subunits form a Schiff base with the substrate indicating that the enzyme exhibits the phenomenon of either half-site reactivity or negative cooperativity. The enzyme appears to have a strong subunit-subunit interaction for an immobilized preparation remained stable for at least a month. An immobilized enzyme preparation was treated in a manner so that it dissociated into tetramers. Both the eluate and protein still attached to the Sepharose on a column were enzymically active. The bound enzyme could not reassociate under assay conditions but still contained about 50% of the original enzyme activity. It would seem that the enzyme is active when composed with less than eight subunits."}
{"id": "PMID:4833", "title": "Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis.", "content": "5-Aminolaevulinate synthetase cataylses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C--C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate (a) undergoes decarboxylation to give the carbanion (b) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine. In pathway B, loss of a C2 hydrogen atom gives another type of carbanion (c) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C--C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine. Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.(Carticle) Several mechanistic alternatices for the formation of the two vinyl groups of haem from the propionate residues of the precursor, coproporphyrinogen III, have been examined. (see article). It is shown that during the biosynthesis both the hydrogen atoms resident at the alpha positions of the propionate side chains remain undisturbed thus eliminating mechanisms which predict the involvement of acrylic acid intermediates. Biosynthetic experiments performed with precursors containing stereospecific labels have shown that the two vinyl groups of haem are formed through the loss of pro S hydrogen atoms from the beta-positions of the propionate side chains. In the light of these results, three related mechanisms for the conversion, propionate leads to vinyl, have been considered. In order to study the mechanism of porphyrinogen carboxy-lyase reaction, stereo-specifically deuterated, tritiated-succinate was incorporated into the acetate residues of uroporphyrinogen III which on decarboxylation generated asymmetric methyl groups in coproporphyrinogen III and then in haem. Degradation of the latter yielded chiral acetate deriving from C and D rings of haem. Configurational analysis of this derivate acetate shows that the carboxy-lyase reaction proceeds with a retention of configuration.", "contents": "Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis. 5-Aminolaevulinate synthetase cataylses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C--C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate (a) undergoes decarboxylation to give the carbanion (b) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine. In pathway B, loss of a C2 hydrogen atom gives another type of carbanion (c) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C--C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine. Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.(Carticle) Several mechanistic alternatices for the formation of the two vinyl groups of haem from the propionate residues of the precursor, coproporphyrinogen III, have been examined. (see article). It is shown that during the biosynthesis both the hydrogen atoms resident at the alpha positions of the propionate side chains remain undisturbed thus eliminating mechanisms which predict the involvement of acrylic acid intermediates. Biosynthetic experiments performed with precursors containing stereospecific labels have shown that the two vinyl groups of haem are formed through the loss of pro S hydrogen atoms from the beta-positions of the propionate side chains. In the light of these results, three related mechanisms for the conversion, propionate leads to vinyl, have been considered. In order to study the mechanism of porphyrinogen carboxy-lyase reaction, stereo-specifically deuterated, tritiated-succinate was incorporated into the acetate residues of uroporphyrinogen III which on decarboxylation generated asymmetric methyl groups in coproporphyrinogen III and then in haem. Degradation of the latter yielded chiral acetate deriving from C and D rings of haem. Configurational analysis of this derivate acetate shows that the carboxy-lyase reaction proceeds with a retention of configuration."}
{"id": "PMID:4834", "title": "Biosynthesis of uroporphyrinogens from porphobilinogen: mechanism and the nature of the process.", "content": "The enzymic self-polymerization of prophobilinogen gives rise to the cyclic tetrapyrroles uroporphyrinogen III and uroporphyrinogen I. The former is the precursor of all the natural porphyrins and chlorins. The formation of uroporphyrinogen III is catalysed by a dual enzymic system, porphobilinogen deaminase and uroporphyrinogen III cosynthase. Deaminase polymerizes four porphobilinogen units on the enzymic surface, without liberation of free intermediates into the reaction medium, and forms uroporphyrinogen I. Cosynthase enters into association with the deaminase, and acts as a 'specifier protein' of the latter, changing the mode of porphobilinogen condensation on the enzymic surface. The association is independent of the presence of substrate. While deaminase catalyses the head-to-tail condensation of the porphobilinogen units, the association deaminase-cosynthase catalyses the head-to-head condensation of the same units. As a result different enzyme-bound dipyrrylmethanes are formed form the beginning of the process, and this can be demonstrated by using synthetic dipyrrylmethanes and tripyrranes.", "contents": "Biosynthesis of uroporphyrinogens from porphobilinogen: mechanism and the nature of the process. The enzymic self-polymerization of prophobilinogen gives rise to the cyclic tetrapyrroles uroporphyrinogen III and uroporphyrinogen I. The former is the precursor of all the natural porphyrins and chlorins. The formation of uroporphyrinogen III is catalysed by a dual enzymic system, porphobilinogen deaminase and uroporphyrinogen III cosynthase. Deaminase polymerizes four porphobilinogen units on the enzymic surface, without liberation of free intermediates into the reaction medium, and forms uroporphyrinogen I. Cosynthase enters into association with the deaminase, and acts as a 'specifier protein' of the latter, changing the mode of porphobilinogen condensation on the enzymic surface. The association is independent of the presence of substrate. While deaminase catalyses the head-to-tail condensation of the porphobilinogen units, the association deaminase-cosynthase catalyses the head-to-head condensation of the same units. As a result different enzyme-bound dipyrrylmethanes are formed form the beginning of the process, and this can be demonstrated by using synthetic dipyrrylmethanes and tripyrranes."}
{"id": "PMID:4835", "title": "Biosynthesis of porphyrins and corrins.", "content": "Haem, chlorophyll and vitamin B12 are all derived ultimately from four molecules of the pyrrole porphobilinogen (PBG) and the initial enzyme catalysed condensation of PBG leads to the unsymmetrical type III isomer of uroporphyrinogen. On the basis of straightforward chemical considerations the type I isomer should be formed and so the porphyrinogen-forming enzymes of all living systems must catalyse a highly specific rearrangement process. The nature and chemical mechanism of this rearrangement poses one of the most fascinating problems in the porphyrin field and so it is not surprising that over 20 hypothetical schemes have been proposed to account for it. Analysis of the problem suggested that the incorporation of doubly 13C-labelled precursors into the rearranged macrocyclic rings would give valuable new information on the nature of the rearrangement process. In this approach the meso=bridge atoms are of crucial importance, and several unambiguous syntheses of 13C-labelled pyrroles and porphyrins were developed to allow rigorous n.m.r. assignments to be made, and also to provide substrates for enzymic experiments. Studies carried out with enzymes from both avian blood and from Euglena gracilis have revealed the precise nature of the assembly of four PBG molecules into the type-III macrocycle: it is the same in both systems despite their vastly different evolutionary development. Complementary studies are in progress in order to determine the intermediates involved in the conversion of PBG into uroporphyrinogen III. The synthesis of amino methyl pyrromethanes and their interaction in the presence of PBG with the appropriate enzyme systems are described. It is important for the work to be able to separate not only isomeric pyrromethanes but also the four isomeric coproporphyrins. Powerful methods are described which make use of high pressure liquid chromatography for both types of separation process. Once uroporhyrinogen III has been built enzymically, there is a stepwise enzymic decarboxylation of the four acetic acid residues. A heptacarboxylic porphyrin shown to be a type-III porphyrin is isolated from the action of avian blood enzymes on porphobilinogen. Spectroscopic studies with 13C-labelling limit the possible structures to two and total synthesis of these substances shows that the natural product carries its methyl group on ring D. An isomeric heptacarboxylic porphyrin having its methyl group on ring C is of particular interest in relation to the biosynthesis of vitamin B12. This substance is synthesized together with uroporphyrin III, 14C-labelled specifically in ring C. This latter product is used to settle one of the key questions concerning nature's route to vitamin B12 - that is, does the corrin macrocycle arise from uroporphyrinogen III? Incorporation studies and specific degradations prove specific incorporation of uroporphyrinogen III into cobyrinic acid, which is the known precursor of vitamin B12.", "contents": "Biosynthesis of porphyrins and corrins. Haem, chlorophyll and vitamin B12 are all derived ultimately from four molecules of the pyrrole porphobilinogen (PBG) and the initial enzyme catalysed condensation of PBG leads to the unsymmetrical type III isomer of uroporphyrinogen. On the basis of straightforward chemical considerations the type I isomer should be formed and so the porphyrinogen-forming enzymes of all living systems must catalyse a highly specific rearrangement process. The nature and chemical mechanism of this rearrangement poses one of the most fascinating problems in the porphyrin field and so it is not surprising that over 20 hypothetical schemes have been proposed to account for it. Analysis of the problem suggested that the incorporation of doubly 13C-labelled precursors into the rearranged macrocyclic rings would give valuable new information on the nature of the rearrangement process. In this approach the meso=bridge atoms are of crucial importance, and several unambiguous syntheses of 13C-labelled pyrroles and porphyrins were developed to allow rigorous n.m.r. assignments to be made, and also to provide substrates for enzymic experiments. Studies carried out with enzymes from both avian blood and from Euglena gracilis have revealed the precise nature of the assembly of four PBG molecules into the type-III macrocycle: it is the same in both systems despite their vastly different evolutionary development. Complementary studies are in progress in order to determine the intermediates involved in the conversion of PBG into uroporphyrinogen III. The synthesis of amino methyl pyrromethanes and their interaction in the presence of PBG with the appropriate enzyme systems are described. It is important for the work to be able to separate not only isomeric pyrromethanes but also the four isomeric coproporphyrins. Powerful methods are described which make use of high pressure liquid chromatography for both types of separation process. Once uroporhyrinogen III has been built enzymically, there is a stepwise enzymic decarboxylation of the four acetic acid residues. A heptacarboxylic porphyrin shown to be a type-III porphyrin is isolated from the action of avian blood enzymes on porphobilinogen. Spectroscopic studies with 13C-labelling limit the possible structures to two and total synthesis of these substances shows that the natural product carries its methyl group on ring D. An isomeric heptacarboxylic porphyrin having its methyl group on ring C is of particular interest in relation to the biosynthesis of vitamin B12. This substance is synthesized together with uroporphyrin III, 14C-labelled specifically in ring C. This latter product is used to settle one of the key questions concerning nature's route to vitamin B12 - that is, does the corrin macrocycle arise from uroporphyrinogen III? Incorporation studies and specific degradations prove specific incorporation of uroporphyrinogen III into cobyrinic acid, which is the known precursor of vitamin B12."}
{"id": "PMID:4836", "title": "Synthesis of probable and improbable precursors for porphyrin biosynthesis.", "content": "Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control. Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated.", "contents": "Synthesis of probable and improbable precursors for porphyrin biosynthesis. Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control. Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated."}
{"id": "PMID:4837", "title": "Macrocyclic intermediates in the biosynthesis of porphyrins.", "content": "The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners.", "contents": "Macrocyclic intermediates in the biosynthesis of porphyrins. The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners."}
{"id": "PMID:4838", "title": "Neovitamin B12 (cyano-13-epicobalamin).", "content": "Beta-Epimerization in the corrinoid system has recently emerged as a complicating factor in the latter stages of the total synthesis of vitamin B12 (Eschenmoser 1971; Woodward 1973). It has also found some application in biosynthetic studies on the origin of the methyl groups in ring C (Scott, Townsend & Cushley 1973; Scott, this Discussion p. 303). This paper sets out to review briefly the beta-epimerization of corrinoid polyamides, with particular reference to our work on the neo-series which provided the first established example of this phenomenon.", "contents": "Neovitamin B12 (cyano-13-epicobalamin). Beta-Epimerization in the corrinoid system has recently emerged as a complicating factor in the latter stages of the total synthesis of vitamin B12 (Eschenmoser 1971; Woodward 1973). It has also found some application in biosynthetic studies on the origin of the methyl groups in ring C (Scott, Townsend & Cushley 1973; Scott, this Discussion p. 303). This paper sets out to review briefly the beta-epimerization of corrinoid polyamides, with particular reference to our work on the neo-series which provided the first established example of this phenomenon."}
{"id": "PMID:4839", "title": "The biosynthesis of vitamin B12.", "content": "The use of 13C-Fourier transform nuclear magnetic resonance (F.t.-n.m.r.) has led to the observation that while 8 molecules of [2-13C]ALA are incorporated into vitamin B12 in P. shermanii, [5-13C]ALA labels only seven of the carbon atoms of cyanocobalamin, i.e. one of the amino methyl groups of ALA is \"lost\" in the process. It has also been confirmed that seven of the methyl groups of B12 are derived from 13CH3-enriched methionine and further that the chirality of the gemdimethyl grouping at C12 labelled with [13CH3]methionine is R. A soluble enzyme mixture from the 37000 or 100000 g supernatant of disrupted cells of P. shermanii converts both 14 C-labelled ALA and [14C]uro'gen III to cobyrinic acid, the simplest corrinoid material on the pathway to vitamin B12 and the coenzyme, in presence of NADPH, Co2+, Mg2+, S-adenosyl-methionine and glutathione. Multiply-labelled uro'gens (13C, 14C and 3H) have been used to show that incorporation takes place without randomization. A sequence for corrin synthesis from uro'gen III is presented.", "contents": "The biosynthesis of vitamin B12. The use of 13C-Fourier transform nuclear magnetic resonance (F.t.-n.m.r.) has led to the observation that while 8 molecules of [2-13C]ALA are incorporated into vitamin B12 in P. shermanii, [5-13C]ALA labels only seven of the carbon atoms of cyanocobalamin, i.e. one of the amino methyl groups of ALA is \"lost\" in the process. It has also been confirmed that seven of the methyl groups of B12 are derived from 13CH3-enriched methionine and further that the chirality of the gemdimethyl grouping at C12 labelled with [13CH3]methionine is R. A soluble enzyme mixture from the 37000 or 100000 g supernatant of disrupted cells of P. shermanii converts both 14 C-labelled ALA and [14C]uro'gen III to cobyrinic acid, the simplest corrinoid material on the pathway to vitamin B12 and the coenzyme, in presence of NADPH, Co2+, Mg2+, S-adenosyl-methionine and glutathione. Multiply-labelled uro'gens (13C, 14C and 3H) have been used to show that incorporation takes place without randomization. A sequence for corrin synthesis from uro'gen III is presented."}
{"id": "PMID:4840", "title": "Synthesis of corrins and related macrocycles based on pyrrolic intermediates.", "content": "Intermediate in structure between porphyrins and corrins are the corroles and 1-methyltetradehydrocorrins. These ring systems, like the porphyrins, can be obtained by cyclization of linear tetrapyrrolic compounds, reactions which have been shown to proceed by orbital symmetry-allowed electrocyclic processes, and examples will be quoted. Thermolysis of nickel 1-methyltetradehydrocorrins causes a migration of the methyl group whereas similar treatment of nickel 1,19-dimethyltetradehydrocorrin salts yields porphyrin derivatives; the mechanisms of these transformations have been elucidated. Stepwise hydrogenation of metal tetradehydrocorrin salts (10 double bonds) yields a series of macrocycles containing 9, 8, 7, 6 and 5 double bonds and conditions necessary to obtain corrins have been established.", "contents": "Synthesis of corrins and related macrocycles based on pyrrolic intermediates. Intermediate in structure between porphyrins and corrins are the corroles and 1-methyltetradehydrocorrins. These ring systems, like the porphyrins, can be obtained by cyclization of linear tetrapyrrolic compounds, reactions which have been shown to proceed by orbital symmetry-allowed electrocyclic processes, and examples will be quoted. Thermolysis of nickel 1-methyltetradehydrocorrins causes a migration of the methyl group whereas similar treatment of nickel 1,19-dimethyltetradehydrocorrin salts yields porphyrin derivatives; the mechanisms of these transformations have been elucidated. Stepwise hydrogenation of metal tetradehydrocorrin salts (10 double bonds) yields a series of macrocycles containing 9, 8, 7, 6 and 5 double bonds and conditions necessary to obtain corrins have been established."}
{"id": "PMID:4841", "title": "Chemical behavior of dicyanocob(III)yrinic acid heptamethyl ester and cob(I)yrinic acid heptamethyl ester in some preparative experiments.", "content": "Preparations of C10 acetate, trifluoroacetate, and chloro derivatives of dicyanocobyrinic acid heptamethyl ester ('cobester') are described. The nature and properties of intermediates in the synthesis of the 10-chloro derivative are discussed, and the electronic absorption spectra of the products are presented.", "contents": "Chemical behavior of dicyanocob(III)yrinic acid heptamethyl ester and cob(I)yrinic acid heptamethyl ester in some preparative experiments. Preparations of C10 acetate, trifluoroacetate, and chloro derivatives of dicyanocobyrinic acid heptamethyl ester ('cobester') are described. The nature and properties of intermediates in the synthesis of the 10-chloro derivative are discussed, and the electronic absorption spectra of the products are presented."}
{"id": "PMID:4842", "title": "Chemical reactivities of tetrapyrrole pigments: a comparison of experimentalbehaviour with the results of s.c.f.-pi-m.o. calculations.", "content": "Porphyrins are highly sigma-electron donating bases and very weak pi-acids. Hence they increase the electron density  on central metal ions, e.g. iron, which leads to the specific reactivity of haem cytochromes, haemoglobin and oxidizing enzymes. The macrocyclic chlorin ligand behaves similarly but to a lesser degree which explains the comparably low oxidation potential of chlorophyll. Phlorins, oxophlorins, oxa- and aza-orphyrins, tetradehydrocorrins, corrins and biliverdins all produce metal complexes which have a similar geometry to that of metalloporphyrins, but their reactivity patterns are different. In contrast to the metalloporphyrins which undergo many fully reversible reactions, these compounds tend to irreversible addition and cleavage reactions. The tetrapyrrole ligands are stronger pi-acids than porphyrins. Results of some recent experimental work and pi-electron s.c.f. calculations are presented in support of these generalizations.", "contents": "Chemical reactivities of tetrapyrrole pigments: a comparison of experimentalbehaviour with the results of s.c.f.-pi-m.o. calculations. Porphyrins are highly sigma-electron donating bases and very weak pi-acids. Hence they increase the electron density  on central metal ions, e.g. iron, which leads to the specific reactivity of haem cytochromes, haemoglobin and oxidizing enzymes. The macrocyclic chlorin ligand behaves similarly but to a lesser degree which explains the comparably low oxidation potential of chlorophyll. Phlorins, oxophlorins, oxa- and aza-orphyrins, tetradehydrocorrins, corrins and biliverdins all produce metal complexes which have a similar geometry to that of metalloporphyrins, but their reactivity patterns are different. In contrast to the metalloporphyrins which undergo many fully reversible reactions, these compounds tend to irreversible addition and cleavage reactions. The tetrapyrrole ligands are stronger pi-acids than porphyrins. Results of some recent experimental work and pi-electron s.c.f. calculations are presented in support of these generalizations."}
{"id": "PMID:4843", "title": "The structures of some cobalamins in solution.", "content": "Nuclear magnetic resonance spectroscopy has been used to examine the conformations of cobalamins in solution. The perturbation of the resonances in the n.m.r. spectra by lanthanide probes provided particularly valuable information. Except for minor details the conformations are the same as those in the crystalline state. The temperature dependence of the conformation has been reassessed.", "contents": "The structures of some cobalamins in solution. Nuclear magnetic resonance spectroscopy has been used to examine the conformations of cobalamins in solution. The perturbation of the resonances in the n.m.r. spectra by lanthanide probes provided particularly valuable information. Except for minor details the conformations are the same as those in the crystalline state. The temperature dependence of the conformation has been reassessed."}
{"id": "PMID:4844", "title": "Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides.", "content": "Rhodopseudomonas spheroides can grow in a defined medium with either light or oxygen as an energy source. Cells grown anaerobically or at very low oxygen tensions are rich in the photosynthetic pigment bacteriochlorophyll, whereas this pigment is virtually absent in cells grown under high oxygen tensions. Aminolaevulinate synthetase, the first enzyme on the pathway to bacteriochlorophyll, appears to play an important role in the control of bacteriochlorophyll synthesis. Thus, the enzyme has a high activity in extracts of pigmented cells and a low activity in extracts of non-pigmented cells. Further, oxygenation of a pigmented culture causes immediate cessation of pigment synthesis and produces a rapid fall in the activity of aminolaevulinate synthetase. This loss of activity appears to be due to the loss of an endogenous activator of the enzyme. Thus, pigmented cells contain cystine trisulphide, which at muM concentrations is an activator of aminolaevulinate synthetase, while oxygenation causes a rapid fall in the cellular content of this trisulphide. Cystathionase (EC 4.2.1.15) extracted from pigmented cells can catalyse the formation of cystine trisulphide from cystine, while rhodanese (EC 2.8.1.1) extracted from the same cells can catalyse the degradation of cystine trisulphide in the presence of sulphite to form cystine and thiosulphate. It is proposed that the cellular content of cystine trisulphide is controlled by changes in the levels of substrates for cystathionase and possibly rhodanese rather than changes in the amounts of these enzymes. Cystine trisulphide controls the activity of aminolaevulinate synthetase by converting a low-activity form of the enzyme (b-form) into a high-activity form (a-form). The fall in aminolaevulinate synthetase activity on oxygenation appears to be the result of cessation of conversion of b-form into a-form, along with a conversion of a-form into b-form. Factors affecting the equilibrium between the forms and the possible mechanisms for their interconversion are discussed.", "contents": "Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides. Rhodopseudomonas spheroides can grow in a defined medium with either light or oxygen as an energy source. Cells grown anaerobically or at very low oxygen tensions are rich in the photosynthetic pigment bacteriochlorophyll, whereas this pigment is virtually absent in cells grown under high oxygen tensions. Aminolaevulinate synthetase, the first enzyme on the pathway to bacteriochlorophyll, appears to play an important role in the control of bacteriochlorophyll synthesis. Thus, the enzyme has a high activity in extracts of pigmented cells and a low activity in extracts of non-pigmented cells. Further, oxygenation of a pigmented culture causes immediate cessation of pigment synthesis and produces a rapid fall in the activity of aminolaevulinate synthetase. This loss of activity appears to be due to the loss of an endogenous activator of the enzyme. Thus, pigmented cells contain cystine trisulphide, which at muM concentrations is an activator of aminolaevulinate synthetase, while oxygenation causes a rapid fall in the cellular content of this trisulphide. Cystathionase (EC 4.2.1.15) extracted from pigmented cells can catalyse the formation of cystine trisulphide from cystine, while rhodanese (EC 2.8.1.1) extracted from the same cells can catalyse the degradation of cystine trisulphide in the presence of sulphite to form cystine and thiosulphate. It is proposed that the cellular content of cystine trisulphide is controlled by changes in the levels of substrates for cystathionase and possibly rhodanese rather than changes in the amounts of these enzymes. Cystine trisulphide controls the activity of aminolaevulinate synthetase by converting a low-activity form of the enzyme (b-form) into a high-activity form (a-form). The fall in aminolaevulinate synthetase activity on oxygenation appears to be the result of cessation of conversion of b-form into a-form, along with a conversion of a-form into b-form. Factors affecting the equilibrium between the forms and the possible mechanisms for their interconversion are discussed."}
{"id": "PMID:4847", "title": "The structural subunit of glucose-6-phosphate dehydrogenase (baker's yeast).", "content": "The subunit molecular weight of glucose-6-phosphate dehydrogenase (G6PD) from baker's yeast has been evaluated. The subunit molecular weight value is shown to be 25,500 daltons by analytical ultracentrifugation, SDS-polyacrylamide gel electrophoresis, and the number of peptides produced by CNBr cleavage. The number of NADP binding sites was determined to be one per 25,500 dalton unit.", "contents": "The structural subunit of glucose-6-phosphate dehydrogenase (baker's yeast). The subunit molecular weight of glucose-6-phosphate dehydrogenase (G6PD) from baker's yeast has been evaluated. The subunit molecular weight value is shown to be 25,500 daltons by analytical ultracentrifugation, SDS-polyacrylamide gel electrophoresis, and the number of peptides produced by CNBr cleavage. The number of NADP binding sites was determined to be one per 25,500 dalton unit."}
{"id": "PMID:4848", "title": "Study of cystinaminopeptidase heterogeneity in animal sera by the isoelectric focusing method.", "content": "Study of the quantitative distribution of cystinaminopeptidase activity in the serum of pregnant and control animals (cow, sheep and rat) by the isoelectric focusing method showed heterogeneity of the cystinaminopeptidase activity of the animals' serum enzymatic system, which was well pronounced in the cow and rat and less pronounced in the sheep. The authors assume from their results that the principal difference between the pregnant and control animals is not the total increase in the level of activity of the enzyme in question, but the shift in its incidence, or the increase in activity at a given pH. It is possible that pregnancy, in man and animals, produces in the serum cystinaminopeptidase system (which is evidently heterogeneous even under normal, physiological conditions) given changes, i.e. the formation of new fractions with a different pI from the controls; other fractions disappear, or their activity diminishes.", "contents": "Study of cystinaminopeptidase heterogeneity in animal sera by the isoelectric focusing method. Study of the quantitative distribution of cystinaminopeptidase activity in the serum of pregnant and control animals (cow, sheep and rat) by the isoelectric focusing method showed heterogeneity of the cystinaminopeptidase activity of the animals' serum enzymatic system, which was well pronounced in the cow and rat and less pronounced in the sheep. The authors assume from their results that the principal difference between the pregnant and control animals is not the total increase in the level of activity of the enzyme in question, but the shift in its incidence, or the increase in activity at a given pH. It is possible that pregnancy, in man and animals, produces in the serum cystinaminopeptidase system (which is evidently heterogeneous even under normal, physiological conditions) given changes, i.e. the formation of new fractions with a different pI from the controls; other fractions disappear, or their activity diminishes."}
{"id": "PMID:4849", "title": "Thiopental anaesthesia and the acid-base balance in the blood of experimental dogs.", "content": "An analysis of basic parameters representative of the acid-base balance was made in arterial blood samples from 140 clinically healthy dogs, under a general intravenous Thiopental anaesthesia. The following mean values +/- S.E.M. were obtained: pH = 7.33 +/- 0.01; pCO2 = 47.16 +/- 0.95; base excess = -2.12 +/- 0.27; buffer base = 46.63 +/- 0.37. The results showed a prevalent trend of lower values of pH, base excess and buffer base and higher values of pCO2 than those found commonly in human clinical practice. Special attention was paid to the respiratory component of the acid-base balance (ABB) revealing certain undesirable side effect of Thiopental anaesthesia.", "contents": "Thiopental anaesthesia and the acid-base balance in the blood of experimental dogs. An analysis of basic parameters representative of the acid-base balance was made in arterial blood samples from 140 clinically healthy dogs, under a general intravenous Thiopental anaesthesia. The following mean values +/- S.E.M. were obtained: pH = 7.33 +/- 0.01; pCO2 = 47.16 +/- 0.95; base excess = -2.12 +/- 0.27; buffer base = 46.63 +/- 0.37. The results showed a prevalent trend of lower values of pH, base excess and buffer base and higher values of pCO2 than those found commonly in human clinical practice. Special attention was paid to the respiratory component of the acid-base balance (ABB) revealing certain undesirable side effect of Thiopental anaesthesia."}
{"id": "PMID:4853", "title": "Fast neutron and x-ray induced single strand DNA breaks in cultured mammalian cells.", "content": "The relative biologic effectiveness (RBE) of fast neutrons in the production of single strand DNA breaks is 1.6 as compared to that of 250 kVp x rays. Monolayers of L-929 cells were treated with dinitrophenol during irradiation to prevent the DNA strands from rejoining; the extent of DNA damage was measured by the alkaline sucrose sedimentation method. The RBE for DNA damage is essentially the same as the RBE measured by cell survival methods.", "contents": "Fast neutron and x-ray induced single strand DNA breaks in cultured mammalian cells. The relative biologic effectiveness (RBE) of fast neutrons in the production of single strand DNA breaks is 1.6 as compared to that of 250 kVp x rays. Monolayers of L-929 cells were treated with dinitrophenol during irradiation to prevent the DNA strands from rejoining; the extent of DNA damage was measured by the alkaline sucrose sedimentation method. The RBE for DNA damage is essentially the same as the RBE measured by cell survival methods."}
{"id": "PMID:4854", "title": "Inhibition of prostaglandin biosynthesis by sulphasalazine and its metabolites.", "content": "Sulphasalazine (SZ) inhibits prostaglandin (PG) biosynthesis in vitro with a potency comparable to that of aceylsalicylate. The metabolites of SZ, sulphapyridine and 5-aminosalicylic acid, were of considerably lower potency as inhibitors of PG biosynthesis in the synthetase preparations used. Th inhibition of prostaglandin production by SZ could at least partly account for the clinical utility of sulphasalazine in ulcerative colitis. Sulphapyridine may help to maintain inhibitory concentrations of SZ by restraining bacterial breakdown of the active drug.", "contents": "Inhibition of prostaglandin biosynthesis by sulphasalazine and its metabolites. Sulphasalazine (SZ) inhibits prostaglandin (PG) biosynthesis in vitro with a potency comparable to that of aceylsalicylate. The metabolites of SZ, sulphapyridine and 5-aminosalicylic acid, were of considerably lower potency as inhibitors of PG biosynthesis in the synthetase preparations used. Th inhibition of prostaglandin production by SZ could at least partly account for the clinical utility of sulphasalazine in ulcerative colitis. Sulphapyridine may help to maintain inhibitory concentrations of SZ by restraining bacterial breakdown of the active drug."}
{"id": "PMID:4855", "title": "Partial characterization of prostaglandin synthetase in the reproductive tract of the male house cricket, Acheta domesticus.", "content": "An active prostaglandin (PG) synthetase was found in the 12100 g pellet of reproductive tract homogenates of the male house cricket, Acheta domesticus. Comparatively, the 12100 g supernatant and the microsomal fractions were inactive. The PG synthetase in the pellet fraction was characterized in terms of cofactor, temperature, pH, and incubation time requirements. Indomethacin, a known inhibitor of mammalian PG synthetase, was not inhibitory to the cricket synthetase. The procedure and findings are relevant to PG synthetase studies of any organism or tissue.", "contents": "Partial characterization of prostaglandin synthetase in the reproductive tract of the male house cricket, Acheta domesticus. An active prostaglandin (PG) synthetase was found in the 12100 g pellet of reproductive tract homogenates of the male house cricket, Acheta domesticus. Comparatively, the 12100 g supernatant and the microsomal fractions were inactive. The PG synthetase in the pellet fraction was characterized in terms of cofactor, temperature, pH, and incubation time requirements. Indomethacin, a known inhibitor of mammalian PG synthetase, was not inhibitory to the cricket synthetase. The procedure and findings are relevant to PG synthetase studies of any organism or tissue."}
{"id": "PMID:4857", "title": "Hydroxyzine hydrochloride: possible adverse cardiac interactions.", "content": "Hydroxyzine hydrochloride may produce abnormal ventricular repolarization when given in substratial doses or to susceptible individuals. Phenothiazines, such as thioridazine, tricyclic antidepressants, or antiparkinson drugs, any of which may be given concurrently to psychiatric patients, may augment this effect as well as atropine, quinidine or procainamide. Such EKG abnormalities may increase the likelihood of dysrhythmias and sudden death.", "contents": "Hydroxyzine hydrochloride: possible adverse cardiac interactions. Hydroxyzine hydrochloride may produce abnormal ventricular repolarization when given in substratial doses or to susceptible individuals. Phenothiazines, such as thioridazine, tricyclic antidepressants, or antiparkinson drugs, any of which may be given concurrently to psychiatric patients, may augment this effect as well as atropine, quinidine or procainamide. Such EKG abnormalities may increase the likelihood of dysrhythmias and sudden death."}
{"id": "PMID:4858", "title": "Assessment of antipsychotic activity of an unique agent: SU-23397.", "content": "SU-23397 is a unique new hybrid molecule, the animal profile being characteristic of neuroleptic activity. Although the trial was uncontrolled, there appears to be no doubt that SU-23397 exerts antipsychotic activity between 20 mg and 250 mg daily in severely ill schizophrenic patients. Seven of the ten subjects required at least transient antiparkinson medication. Two patients demonstrated premature ventricular contractions. One patient had infrequent PVCs at baseline which increased in frequency with rising dosage. The other patient developed frequent premature ventricular contractions only after active and medication was initiated and was subsequently withdrawn from the study.", "contents": "Assessment of antipsychotic activity of an unique agent: SU-23397. SU-23397 is a unique new hybrid molecule, the animal profile being characteristic of neuroleptic activity. Although the trial was uncontrolled, there appears to be no doubt that SU-23397 exerts antipsychotic activity between 20 mg and 250 mg daily in severely ill schizophrenic patients. Seven of the ten subjects required at least transient antiparkinson medication. Two patients demonstrated premature ventricular contractions. One patient had infrequent PVCs at baseline which increased in frequency with rising dosage. The other patient developed frequent premature ventricular contractions only after active and medication was initiated and was subsequently withdrawn from the study."}
{"id": "PMID:4859", "title": "The effect of various chlorpromazine derivatives on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity.", "content": "The effects of chlorpromazine and of some metabolites of chlorpromazine on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity were investigated. Chlorpromazine, nor1-chlorpromazine and 7-hydroxychlorpromazine reverse the apomorphine-elicited inhibition of tyrosine hydroxylase activity while nor1-chlorpromazine sulfoxide and nor2-chlorpromazine sulfoxide have no effect on this inhibition. 6-Hydroxychlorpromazine and promethazine also reverse the enzyme inhibition by apomorphine but are less potent than chlorpromazine or 7-hydroxychlorpromazine. These results show that chlorpromazine and its metabolites with antipsychotic activity are more effective in reversing the apomorphine-elicited inhibition of tyrosine hydroxylase than those metabolites which are devoid of antipsychotic activity.", "contents": "The effect of various chlorpromazine derivatives on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. The effects of chlorpromazine and of some metabolites of chlorpromazine on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity were investigated. Chlorpromazine, nor1-chlorpromazine and 7-hydroxychlorpromazine reverse the apomorphine-elicited inhibition of tyrosine hydroxylase activity while nor1-chlorpromazine sulfoxide and nor2-chlorpromazine sulfoxide have no effect on this inhibition. 6-Hydroxychlorpromazine and promethazine also reverse the enzyme inhibition by apomorphine but are less potent than chlorpromazine or 7-hydroxychlorpromazine. These results show that chlorpromazine and its metabolites with antipsychotic activity are more effective in reversing the apomorphine-elicited inhibition of tyrosine hydroxylase than those metabolites which are devoid of antipsychotic activity."}
{"id": "PMID:4860", "title": "Effects of benzodiazepines on the binding of tryptophan in serum. Consequences on 5-hydroxyindoles concentrations in the rat brain.", "content": "Benzodiazepines (diazepam, oxazepam, chlordiazepoxide) inhibited competitively the binding of tryptophan onto rat serum albumin. As a result, in vivo treatment with one of these compounds (chlordiazepoxide for instance) induced a significant increase in the concentration of free tryptophan in serum. These observations suggest that the high levels of both 5-hydroxyindoles and tryptophan which occurred in the rat brain after any benzodiazepine administration could be at least partly the consequence of its effect on tryptophan binding in blood.", "contents": "Effects of benzodiazepines on the binding of tryptophan in serum. Consequences on 5-hydroxyindoles concentrations in the rat brain. Benzodiazepines (diazepam, oxazepam, chlordiazepoxide) inhibited competitively the binding of tryptophan onto rat serum albumin. As a result, in vivo treatment with one of these compounds (chlordiazepoxide for instance) induced a significant increase in the concentration of free tryptophan in serum. These observations suggest that the high levels of both 5-hydroxyindoles and tryptophan which occurred in the rat brain after any benzodiazepine administration could be at least partly the consequence of its effect on tryptophan binding in blood."}
{"id": "PMID:4861", "title": "The search for the dopamine receptor: tribulations.", "content": "In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect.", "contents": "The search for the dopamine receptor: tribulations. In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect."}
{"id": "PMID:4862", "title": "Functional heterogeneity within neurotransmitter systems.", "content": "This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising.", "contents": "Functional heterogeneity within neurotransmitter systems. This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising."}
{"id": "PMID:4863", "title": "Benzodiazepines and reproduction of swiss-webster mice.", "content": "Chronic dietary administration of 6 different benzodiazepine tranquilizers (chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, and nitrazepam) to breeding pairs of Swiss-Webster mice resulted in alterations of the normal patterns of reproductive behavior and fetal growth. Significant decreases in mating performance were seen among mice given diets containing 0.15% chlordiazepoxide, 0.05% diazepam, 0.05 and 0.15% oxazepam, 0.02 and 0.10% prazepam, 0.10% flurazepam, and 0.025% nitrazepam. Offspring in all drug treatments showed significantly depressed body weights at birth.", "contents": "Benzodiazepines and reproduction of swiss-webster mice. Chronic dietary administration of 6 different benzodiazepine tranquilizers (chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, and nitrazepam) to breeding pairs of Swiss-Webster mice resulted in alterations of the normal patterns of reproductive behavior and fetal growth. Significant decreases in mating performance were seen among mice given diets containing 0.15% chlordiazepoxide, 0.05% diazepam, 0.05 and 0.15% oxazepam, 0.02 and 0.10% prazepam, 0.10% flurazepam, and 0.025% nitrazepam. Offspring in all drug treatments showed significantly depressed body weights at birth."}
{"id": "PMID:4864", "title": "In vitro and in vivo studies of (1-sarcosine, 8-threonine) angiotensin II.", "content": "The capacity of (1-Sarcosine, 8-Threonine) angiotensin II to block the contractile and pressor effects of exogenous and endogenous angiotensin II was examined. In isolated rabbit aorta, the pA2 value (from pA2 plots) for the analog was 8.75 +/- 0.11. Both the maximum response and the slope of the dose-response curve to angiotensin II were unchanged by the analog. In ganglion-blocked vagotomized rats, infusion of the analog produced a dose-dependent blockage of the angiotensin II pressor effect. In these rats, the analog displayed less agonistic activity than that of (1-Sarcosine, 8-Isoleucine) and (1-Sarcosine, 8-Alanine) angiotensin II. In two-kidney hypertensive rats, the angiotensin II antagonist significantly reduced the arterial blood pressure. The results indicate that (1-Sar, 8-Thr) angiotensin II is a potent antagonist of angiotensin II with less inherent agonistic activity than previously reported analogs.", "contents": "In vitro and in vivo studies of (1-sarcosine, 8-threonine) angiotensin II. The capacity of (1-Sarcosine, 8-Threonine) angiotensin II to block the contractile and pressor effects of exogenous and endogenous angiotensin II was examined. In isolated rabbit aorta, the pA2 value (from pA2 plots) for the analog was 8.75 +/- 0.11. Both the maximum response and the slope of the dose-response curve to angiotensin II were unchanged by the analog. In ganglion-blocked vagotomized rats, infusion of the analog produced a dose-dependent blockage of the angiotensin II pressor effect. In these rats, the analog displayed less agonistic activity than that of (1-Sarcosine, 8-Isoleucine) and (1-Sarcosine, 8-Alanine) angiotensin II. In two-kidney hypertensive rats, the angiotensin II antagonist significantly reduced the arterial blood pressure. The results indicate that (1-Sar, 8-Thr) angiotensin II is a potent antagonist of angiotensin II with less inherent agonistic activity than previously reported analogs."}
{"id": "PMID:4865", "title": "The effect of mercuric chloride intoxication on urinary psi-glutamyl transpeptidase excretion in the sheep.", "content": "The activity of the enzyme psi-glutamyl transpeptidase (psi-GT) was measured in the urine of sheep. In clinically normal animals the mean value was 6-3+/-0-6 mU/ml. In sheep with  kidney damage induced by the administration of mercuric chloride there were marked increases in urinary concentrations of psi-GT, in some cases values in excess of 1000 mU/ml were recorded. This enzyme may be of value in the diagnosis of certain forms of renal disease.", "contents": "The effect of mercuric chloride intoxication on urinary psi-glutamyl transpeptidase excretion in the sheep. The activity of the enzyme psi-glutamyl transpeptidase (psi-GT) was measured in the urine of sheep. In clinically normal animals the mean value was 6-3+/-0-6 mU/ml. In sheep with  kidney damage induced by the administration of mercuric chloride there were marked increases in urinary concentrations of psi-GT, in some cases values in excess of 1000 mU/ml were recorded. This enzyme may be of value in the diagnosis of certain forms of renal disease."}
{"id": "PMID:4880", "title": "Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease.", "content": "Nucleotide pyrophosphatase activity with uridine diphosphoglucose and dephospho-CoA as substrates was demonstrated in normal human serum. The enzyme has a pH-optimum of about 9.6 and is inhibited by EDTA. Phosphodiesterase I (hydrolysis of thymidine-5'-monophospho-p-nitrophenylester) was also found in normal human serum, with a pH-optimum of about 9.8 and a Km of 0.20-0.25 mM. Probably both activities should be attributed to one enzyme. Different isoenzymes may exist, however. The activity of nucleotide pyrophosphatase/phosphodiesterase I in normal serum in many respects resembles an enzyme previously isolated from liver plasma membranes. Phosphodiesterase I activity was increased in normal pregnancy, in primary biliary cirrhosis, and in patients with bone lesions, but not in acute viral hepatitis or active chronic hepatitis. In primary biliary cirrhosis, the activity of phosphodiesterase I paralleled an increase of alkaline phosphatases.", "contents": "Nucleotide pyrophosphatase and phosphodiesterase I. Demonstration of activity in normal serum, and an increase in cholestatic liver disease. Nucleotide pyrophosphatase activity with uridine diphosphoglucose and dephospho-CoA as substrates was demonstrated in normal human serum. The enzyme has a pH-optimum of about 9.6 and is inhibited by EDTA. Phosphodiesterase I (hydrolysis of thymidine-5'-monophospho-p-nitrophenylester) was also found in normal human serum, with a pH-optimum of about 9.8 and a Km of 0.20-0.25 mM. Probably both activities should be attributed to one enzyme. Different isoenzymes may exist, however. The activity of nucleotide pyrophosphatase/phosphodiesterase I in normal serum in many respects resembles an enzyme previously isolated from liver plasma membranes. Phosphodiesterase I activity was increased in normal pregnancy, in primary biliary cirrhosis, and in patients with bone lesions, but not in acute viral hepatitis or active chronic hepatitis. In primary biliary cirrhosis, the activity of phosphodiesterase I paralleled an increase of alkaline phosphatases."}
{"id": "PMID:4881", "title": "[The value of renin determination in the diagnosis of hypertension].", "content": "Primary aldosteronism and renovascular hypertension are two different diseases in which renin determinations are necessary for establishment of diagnosis or therapeutic procedure. Low renin values which are not stimulated by acute stimuli combined with elevated plasma aldosterone concentrations confirm the diagnosis of primary aldosteronism. When in a patient with proven renal artery stenosis a significant difference in renal venous renin activity is observed between the two kidneys, a connection between hypertension and renal artery stenosis is likely when in addition the renin secretion of the unaffected kidney is suppressed. A favourable outcome for surgery can be predicted when the individual clinical picture in such a case is also considered. A similar view also holds for the connection between hypertension and unilateral small kidney not due to renal artery stenosis. In essential hypertension the plasma renin level makes it possible to a certain extent to predict whether a patient will benefit from diuretics or from beta-blocking agents. Despite this experience, however, renin determinations are not indicated in every case of essential hypertension. It has not been proven that the prognosis of this disease is improved by renin oriented monotherapy rather than by effective treatment with other antihypertensive agents.", "contents": "[The value of renin determination in the diagnosis of hypertension]. Primary aldosteronism and renovascular hypertension are two different diseases in which renin determinations are necessary for establishment of diagnosis or therapeutic procedure. Low renin values which are not stimulated by acute stimuli combined with elevated plasma aldosterone concentrations confirm the diagnosis of primary aldosteronism. When in a patient with proven renal artery stenosis a significant difference in renal venous renin activity is observed between the two kidneys, a connection between hypertension and renal artery stenosis is likely when in addition the renin secretion of the unaffected kidney is suppressed. A favourable outcome for surgery can be predicted when the individual clinical picture in such a case is also considered. A similar view also holds for the connection between hypertension and unilateral small kidney not due to renal artery stenosis. In essential hypertension the plasma renin level makes it possible to a certain extent to predict whether a patient will benefit from diuretics or from beta-blocking agents. Despite this experience, however, renin determinations are not indicated in every case of essential hypertension. It has not been proven that the prognosis of this disease is improved by renin oriented monotherapy rather than by effective treatment with other antihypertensive agents."}
{"id": "PMID:4894", "title": "Alpha-adrenergic receptor identification by (3H)dihydroergocryptine binding.", "content": "A radioactively labeled alpha-adrenergic antagonist, [3H]dihydroergocryptine, binds specifically to a site on rabbit uterine membranes. Binding is rapid, reaching equilibrium in less than 17 minutes at 25 degrees C. Adrenergic agonists compete for this binding site with an order of affinities identical to the pharmacological potency order of these agents as alpha-adrenergic agonists (epinephrine greater than norepinephrine greater than isoprotereonl). The (-) stereoisomers of epinephrine and norepinephrine are 30 times more potent in competing for the site than the corresponding (+) stereoisomers. alpha-Adrenergic antagonists, such as phentolamine and phenoxybenzamine, potently compete for the binding sites while the beta-adrenergic antagonist propranolol does not. Structural analogs of catecholamines that are devoid of alpha-adrenergic physiological activity do not compete for [3H]dihydroergocryptine binding sites. These data suggest that alpha-adrenergic receptors can be directly identified and studied by [3H]dihydroergocryptine binding.", "contents": "Alpha-adrenergic receptor identification by (3H)dihydroergocryptine binding. A radioactively labeled alpha-adrenergic antagonist, [3H]dihydroergocryptine, binds specifically to a site on rabbit uterine membranes. Binding is rapid, reaching equilibrium in less than 17 minutes at 25 degrees C. Adrenergic agonists compete for this binding site with an order of affinities identical to the pharmacological potency order of these agents as alpha-adrenergic agonists (epinephrine greater than norepinephrine greater than isoprotereonl). The (-) stereoisomers of epinephrine and norepinephrine are 30 times more potent in competing for the site than the corresponding (+) stereoisomers. alpha-Adrenergic antagonists, such as phentolamine and phenoxybenzamine, potently compete for the binding sites while the beta-adrenergic antagonist propranolol does not. Structural analogs of catecholamines that are devoid of alpha-adrenergic physiological activity do not compete for [3H]dihydroergocryptine binding sites. These data suggest that alpha-adrenergic receptors can be directly identified and studied by [3H]dihydroergocryptine binding."}
{"id": "PMID:4895", "title": "Aspartate: distinct receptors on Aplysia neurons.", "content": "Aplysia neurons have specific aspartate receptors that are distinct from those to glutamate. In some cells, asparate selectively increases the membrane permeability to chloride, giving rise to a hyperpolarization, while on other cells it increases the permeability to sodium, causing a depolarization. There are also specific receptors for L-glutamate which mediate sodium, chloride, or potassium conductance increases, and another class of receptors activated by both glutamate and aspartate.", "contents": "Aspartate: distinct receptors on Aplysia neurons. Aplysia neurons have specific aspartate receptors that are distinct from those to glutamate. In some cells, asparate selectively increases the membrane permeability to chloride, giving rise to a hyperpolarization, while on other cells it increases the permeability to sodium, causing a depolarization. There are also specific receptors for L-glutamate which mediate sodium, chloride, or potassium conductance increases, and another class of receptors activated by both glutamate and aspartate."}
{"id": "PMID:4896", "title": "Reduction in myocardial infarct size: prevention of heart cell death.", "content": "The course of myocardial necrosis, the clinical syndrome, and methods of treatment are presented. Heart cell death may be prevented by maintaining the balance between myocardial oxygen and energy supply and consumption. New technics of improving this balance by reducing myocardial energy demand, altering metabolism, increasing myocardial substrate supply, and protecting cellular integrity are discussed.", "contents": "Reduction in myocardial infarct size: prevention of heart cell death. The course of myocardial necrosis, the clinical syndrome, and methods of treatment are presented. Heart cell death may be prevented by maintaining the balance between myocardial oxygen and energy supply and consumption. New technics of improving this balance by reducing myocardial energy demand, altering metabolism, increasing myocardial substrate supply, and protecting cellular integrity are discussed."}
{"id": "PMID:4897", "title": "Hypo-acidity of gastric juice in chronic gastric ulceration caused by neutralisation.", "content": "Samples of gastric juice were aspirated every 15 minutes from 54 normal subjects and 31 patients with chronic gastric ulcers during a maximal histamine infusion test. The known tendency of patients with gastric ulcers to secrete a less acid gastric juice than that of normal subjects was confirmed. However, the hypo-acidity was related to the extent by which the total ionic concentration was less than the isotonic value of 328 mEq/l. On the assumption that such hypo-acidity was produced by the neutralisation of hydrogen ions by bicarbonate ions refluxing into the stomach from the duodenum, the data were corrected and resulted in a normal estimate of the hydrogen ion concentration in the gastric ulcer group. Independent corrections, according to the sodium content of refluxed duodenal juice, yielded similar results for the volume of gastric juice aspirated. It is concluded that while back-diffusion can explain the hypo-acidity of gastric juice in patients with gastric ulcers, duodenal reflux can explain both the hypo-acidity and the hypotonicity, and is therefore more likely to be the correct explanation.", "contents": "Hypo-acidity of gastric juice in chronic gastric ulceration caused by neutralisation. Samples of gastric juice were aspirated every 15 minutes from 54 normal subjects and 31 patients with chronic gastric ulcers during a maximal histamine infusion test. The known tendency of patients with gastric ulcers to secrete a less acid gastric juice than that of normal subjects was confirmed. However, the hypo-acidity was related to the extent by which the total ionic concentration was less than the isotonic value of 328 mEq/l. On the assumption that such hypo-acidity was produced by the neutralisation of hydrogen ions by bicarbonate ions refluxing into the stomach from the duodenum, the data were corrected and resulted in a normal estimate of the hydrogen ion concentration in the gastric ulcer group. Independent corrections, according to the sodium content of refluxed duodenal juice, yielded similar results for the volume of gastric juice aspirated. It is concluded that while back-diffusion can explain the hypo-acidity of gastric juice in patients with gastric ulcers, duodenal reflux can explain both the hypo-acidity and the hypotonicity, and is therefore more likely to be the correct explanation."}
{"id": "PMID:4898", "title": "Antihypertensive therapy with timolol and alpha-methyldopa. A double-blind trial in patients with moderately severe hypertension.", "content": "After 24 moderately severe hypertensive patients had been treated for 4 weeks with a placebo for timolol, alpha-methyldopa was added and titrated until control of the blood pressure or a total daily dose of 2 500 mg was achieved. At the 9th week, the dose of alpha-methyldopa was halved and either timolol or its placebo was titrated in double-blind fashion. Titration over a period of 4 weeks was followed by a further 5 weeks of stabilisation. In 22 patients whose responses were accepted for analysis, alpha-methyldopa caused a significant lowering of blood pressure, with a greater reduction in the upright posture and a reduction in pulse rate. The addition of timolol caused a highly significant further reduction in pulse rate and a significant reduction in blood pressure in 8 of 10 patients. Apart from a statistically significant increase in serum urea and creatinine with, however, retention of normal renal function, no other side-effects were attributable to timolol.", "contents": "Antihypertensive therapy with timolol and alpha-methyldopa. A double-blind trial in patients with moderately severe hypertension. After 24 moderately severe hypertensive patients had been treated for 4 weeks with a placebo for timolol, alpha-methyldopa was added and titrated until control of the blood pressure or a total daily dose of 2 500 mg was achieved. At the 9th week, the dose of alpha-methyldopa was halved and either timolol or its placebo was titrated in double-blind fashion. Titration over a period of 4 weeks was followed by a further 5 weeks of stabilisation. In 22 patients whose responses were accepted for analysis, alpha-methyldopa caused a significant lowering of blood pressure, with a greater reduction in the upright posture and a reduction in pulse rate. The addition of timolol caused a highly significant further reduction in pulse rate and a significant reduction in blood pressure in 8 of 10 patients. Apart from a statistically significant increase in serum urea and creatinine with, however, retention of normal renal function, no other side-effects were attributable to timolol."}
{"id": "PMID:4900", "title": "Iatrogenic cryptorchidism resulting from hernia repair.", "content": "Nine children have been examined for iatrogenic cryptorchidism during a four year period. Wound infection and testicular retractility appear to be factors predisposing to this complication. Routine testicular palpation for position at the completion of hernia repair and the use of orchidopexy in selected patients should aid in the prevention of this problem.", "contents": "Iatrogenic cryptorchidism resulting from hernia repair. Nine children have been examined for iatrogenic cryptorchidism during a four year period. Wound infection and testicular retractility appear to be factors predisposing to this complication. Routine testicular palpation for position at the completion of hernia repair and the use of orchidopexy in selected patients should aid in the prevention of this problem."}
{"id": "PMID:4901", "title": "The effect of antihistamines on experimental posttraumatic edema of the spinal cord.", "content": "The present experiments were designed to test the effect of antihistamines on the formation of post-traumatic edema of the spinal cord. Ten rhesus monkeys received 600 gm cm injuries to the T10 level of the spinal cord. Five animals received antihistamine treatment and five animals acted as untreated controls. Posttraumatic edema was estimated using radio-active tagged serum albumin. A significant increase in radioactivity of the injured segment was demonstrated in both groups when compared to noninjured issue, but no difference was demonstrated in the radioactivity of the injured segment in the treated versus the nontreated group.", "contents": "The effect of antihistamines on experimental posttraumatic edema of the spinal cord. The present experiments were designed to test the effect of antihistamines on the formation of post-traumatic edema of the spinal cord. Ten rhesus monkeys received 600 gm cm injuries to the T10 level of the spinal cord. Five animals received antihistamine treatment and five animals acted as untreated controls. Posttraumatic edema was estimated using radio-active tagged serum albumin. A significant increase in radioactivity of the injured segment was demonstrated in both groups when compared to noninjured issue, but no difference was demonstrated in the radioactivity of the injured segment in the treated versus the nontreated group."}
{"id": "PMID:4904", "title": "Chemical studies of marine invertebrates. XVI. Structure and absolute configuration of lobosterol, a novel polyoxygenated sterol from the alcyonacean Lobophytum pauciflorum (clelenterata, octocorallia).", "content": "Lobosterol [(24S)-24-methylcholestane-3beta,4beta,5beta,25-tetrol-6-one 25 monoacetate] has been isolated from the Alcyonacean Lobophytum pauciflorum. The structural elucidation of this novel polyoxygenated sterol was achieved by chemical and spectroscopic evidence, and by X-ray diffraction analysis.", "contents": "Chemical studies of marine invertebrates. XVI. Structure and absolute configuration of lobosterol, a novel polyoxygenated sterol from the alcyonacean Lobophytum pauciflorum (clelenterata, octocorallia). Lobosterol [(24S)-24-methylcholestane-3beta,4beta,5beta,25-tetrol-6-one 25 monoacetate] has been isolated from the Alcyonacean Lobophytum pauciflorum. The structural elucidation of this novel polyoxygenated sterol was achieved by chemical and spectroscopic evidence, and by X-ray diffraction analysis."}
{"id": "PMID:4905", "title": "Irreversible protein binding of norethisterone (norethindrone) epoxide.", "content": "14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins.", "contents": "Irreversible protein binding of norethisterone (norethindrone) epoxide. 14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins."}
{"id": "PMID:4906", "title": "Hydroxyapatite - a reagent for the separation of free and antibody-bound steroid during the radioimmunoassay.", "content": "The use of hydroxyapatite to absorb antibody-bound steroid and thus separate free and antibody-bound steroid during radioimmunoassay has been examined using three steroid antisera (to testosterone, to 17-hydroxyprogesterone and to estradiol-17beta). For all three antisera studied the separation was shown to be independent of length of time in contact with hydroxyapatite (up to 1h); temperature variations from 4 degrees -37 degrees and pH over the range 4.9-8.0. The presence of protein affected the absorption of antibody-bound steroid but this effect could be overcome by the addition of increasing amounts of hydroxyapatite. Further increase in the amount of hydroxyapatite added had no effect on the separation of free and bound steroid. Sodium phosphate buffers of molarity greater than 0.01M eluted antibody-bount steroid from hydroxyapatite, but Tris-HC1 buffers up to molarities of 0.1 M had no effect. Hydroxyapatite when used as a dry powder had the same effects as suspensions. No effect on the cross-reactivities of the antisera used could be demonstrated when hydroxyapatite was used and plasma testosterone assays on 22 plasma samples using hydroxyapatite gave essentially the same results as assays on the plasma using a coated-tube assay. Hydroxyapatite can also be successfully pumped along small bore plastic tubing without settling and can thus be used in automated immunoassay systems.", "contents": "Hydroxyapatite - a reagent for the separation of free and antibody-bound steroid during the radioimmunoassay. The use of hydroxyapatite to absorb antibody-bound steroid and thus separate free and antibody-bound steroid during radioimmunoassay has been examined using three steroid antisera (to testosterone, to 17-hydroxyprogesterone and to estradiol-17beta). For all three antisera studied the separation was shown to be independent of length of time in contact with hydroxyapatite (up to 1h); temperature variations from 4 degrees -37 degrees and pH over the range 4.9-8.0. The presence of protein affected the absorption of antibody-bound steroid but this effect could be overcome by the addition of increasing amounts of hydroxyapatite. Further increase in the amount of hydroxyapatite added had no effect on the separation of free and bound steroid. Sodium phosphate buffers of molarity greater than 0.01M eluted antibody-bount steroid from hydroxyapatite, but Tris-HC1 buffers up to molarities of 0.1 M had no effect. Hydroxyapatite when used as a dry powder had the same effects as suspensions. No effect on the cross-reactivities of the antisera used could be demonstrated when hydroxyapatite was used and plasma testosterone assays on 22 plasma samples using hydroxyapatite gave essentially the same results as assays on the plasma using a coated-tube assay. Hydroxyapatite can also be successfully pumped along small bore plastic tubing without settling and can thus be used in automated immunoassay systems."}
{"id": "PMID:4907", "title": "Influence of adrenergic receptor blockade on circulatory and metabolic effects of disordered neurotransmitter function in stroke patients.", "content": "Cerebral hemispheric blood flow and metabolism were measured before and after therapy with intracarotid infusion of combined PBZ and PPL in 15 patients with recent cerebral infarction. HBF was unaltered despite decrease in cerebral perfusion pressure. Cerebral hemispheric oxygen comsumption and carbon dioxide production decreased while cerebral hemispheric lactate production increased. Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion. CSF HVA increased, indicating altered DA turnover. CSF 5HIAA levels also increased, suggesting altered 5HT turnover after PBZ and PPL. Release of cyclic AMP from ischemic brain into cerebral venous blood seen in the steady state was abolished after therapy. Cerebral hemodynamic studies suggest a functional balance between monaminergic neurogenic influences in the control of cerebral circulation. Imbalance of such controlling factors in ischemic brain may lead to paradoxical vascular responses to induced hypertension and hypotension. PBZ and PPL enhance such responses perhaps by increasing central neurotransmitter turnover and release. Further shift toward cerebral anaerobic metabolism may occur in ischemic brain following the use of phenoxybenzamine and propranolol. Worsening of neurological deficit occurred in four cases. Combined therapy with PBZ and PPL does not appear beneficial in the therapy of patients with recent stroke.", "contents": "Influence of adrenergic receptor blockade on circulatory and metabolic effects of disordered neurotransmitter function in stroke patients. Cerebral hemispheric blood flow and metabolism were measured before and after therapy with intracarotid infusion of combined PBZ and PPL in 15 patients with recent cerebral infarction. HBF was unaltered despite decrease in cerebral perfusion pressure. Cerebral hemispheric oxygen comsumption and carbon dioxide production decreased while cerebral hemispheric lactate production increased. Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion. CSF HVA increased, indicating altered DA turnover. CSF 5HIAA levels also increased, suggesting altered 5HT turnover after PBZ and PPL. Release of cyclic AMP from ischemic brain into cerebral venous blood seen in the steady state was abolished after therapy. Cerebral hemodynamic studies suggest a functional balance between monaminergic neurogenic influences in the control of cerebral circulation. Imbalance of such controlling factors in ischemic brain may lead to paradoxical vascular responses to induced hypertension and hypotension. PBZ and PPL enhance such responses perhaps by increasing central neurotransmitter turnover and release. Further shift toward cerebral anaerobic metabolism may occur in ischemic brain following the use of phenoxybenzamine and propranolol. Worsening of neurological deficit occurred in four cases. Combined therapy with PBZ and PPL does not appear beneficial in the therapy of patients with recent stroke."}
{"id": "PMID:4913", "title": "Action of beta-adrenergic blocking agents on the urethral pressure profile.", "content": "The action of beta-adrenergic blocking agents on the urethral pressure profile was studied. Sotalol, 20 mg, and inderal, 7 mg, were administered intravenously. Whereas the alpha-adrenergic blocking drug phentolamine, as already known, changed the maximum value of the pressure profile with an average decrease of 33%, the beta-adrenergic blocking drugs did not show any action at all. There was no difference between the results obtained with Sotalol and Inderal.", "contents": "Action of beta-adrenergic blocking agents on the urethral pressure profile. The action of beta-adrenergic blocking agents on the urethral pressure profile was studied. Sotalol, 20 mg, and inderal, 7 mg, were administered intravenously. Whereas the alpha-adrenergic blocking drug phentolamine, as already known, changed the maximum value of the pressure profile with an average decrease of 33%, the beta-adrenergic blocking drugs did not show any action at all. There was no difference between the results obtained with Sotalol and Inderal."}
{"id": "PMID:4914", "title": "[Urodynamic measurements in enuretics].", "content": "Distal urethral stenosis in girls as well as meatal and bulbar narrowed urethral segments in boys are still subjects of discussion about their pathologic value in the literature. The urodynamic findings in enuretic children by urethral pressure profile and cystometry frequently point to a outflow resistance. Calibration with bougies \u00e0 boule, urethroscopy and permictional cysturethrography disclose such urethral narrowing. The survey of our own 107 enuritic children shows that urethrotomy has given good results relative to urodynamic data. The effect of methantheline medications consists in suppressing the hyperactivity of the detrusor.", "contents": "[Urodynamic measurements in enuretics]. Distal urethral stenosis in girls as well as meatal and bulbar narrowed urethral segments in boys are still subjects of discussion about their pathologic value in the literature. The urodynamic findings in enuretic children by urethral pressure profile and cystometry frequently point to a outflow resistance. Calibration with bougies \u00e0 boule, urethroscopy and permictional cysturethrography disclose such urethral narrowing. The survey of our own 107 enuritic children shows that urethrotomy has given good results relative to urodynamic data. The effect of methantheline medications consists in suppressing the hyperactivity of the detrusor."}
{"id": "PMID:4915", "title": "Conservative bladder treatment in myelodysplasia. Differentiation of patients by cystomanometry.", "content": "Urodynamic evaluation was performed in 75 patients with congenital neuropathic bladder. Concerning treatment the most important parameters were detrusor tone, detrusor activity and bladder outlet resistance. Based on these findings individual conservative therapy was applied. Reflux or dilatation of the upper urinary tract found in 26 children could be controlled by drugs or transurethral operations in 20, urinary diversion had to be done only 4 times. 26 children were selected for intensive treatment of incontinence; in about 50% satisfying urinary control was achieved. These results still need long-term observation. The main interest, however, was to postpone irreversible surgery and to gain time for possible better treatment in the future.", "contents": "Conservative bladder treatment in myelodysplasia. Differentiation of patients by cystomanometry. Urodynamic evaluation was performed in 75 patients with congenital neuropathic bladder. Concerning treatment the most important parameters were detrusor tone, detrusor activity and bladder outlet resistance. Based on these findings individual conservative therapy was applied. Reflux or dilatation of the upper urinary tract found in 26 children could be controlled by drugs or transurethral operations in 20, urinary diversion had to be done only 4 times. 26 children were selected for intensive treatment of incontinence; in about 50% satisfying urinary control was achieved. These results still need long-term observation. The main interest, however, was to postpone irreversible surgery and to gain time for possible better treatment in the future."}
{"id": "PMID:4929", "title": "[Treatment of hypertonus in diabetes mellitus].", "content": "When pathophysiological and pathogenetic aspects of hypertension are taken into consideration with special regard to diabetes mellitus the exhaustion of the \"insulin enhancement\" within the cerebrovisceral functional systems (Baumann) are discussed and the authors enter possible connections of diabetes mellitus to the renin-angiotensin-aldosterone system. After explanation of the diabetogenic and antidiabetogenic pharmacodynamic qualities of the antihypertensive drugs adequate therapeutic recommendations are proposed summarized in a figure. The authors conclude that for the present antihypertensive therapy in diabetics taking into consideration the references reported on there are sufficient possibilities of treatment for all degrees of severity of hypertension. Such preparations as Rausedan, Disotat, Dopegyt appear as particularly suitable; moreover, the beta receptor blockers, Haemiton, Depressan as well as Guanitil and Pargylin prove to be possible or without disadvantage, respectively. Especially when diuretics are described an exact control of the metabolism should be carried out.", "contents": "[Treatment of hypertonus in diabetes mellitus]. When pathophysiological and pathogenetic aspects of hypertension are taken into consideration with special regard to diabetes mellitus the exhaustion of the \"insulin enhancement\" within the cerebrovisceral functional systems (Baumann) are discussed and the authors enter possible connections of diabetes mellitus to the renin-angiotensin-aldosterone system. After explanation of the diabetogenic and antidiabetogenic pharmacodynamic qualities of the antihypertensive drugs adequate therapeutic recommendations are proposed summarized in a figure. The authors conclude that for the present antihypertensive therapy in diabetics taking into consideration the references reported on there are sufficient possibilities of treatment for all degrees of severity of hypertension. Such preparations as Rausedan, Disotat, Dopegyt appear as particularly suitable; moreover, the beta receptor blockers, Haemiton, Depressan as well as Guanitil and Pargylin prove to be possible or without disadvantage, respectively. Especially when diuretics are described an exact control of the metabolism should be carried out."}
{"id": "PMID:4930", "title": "[The reaction of chorion epitheliums of human placentae to beta-sympathocomimetics (author's transl)].", "content": "The enzyme histochemical response of chorionic epithelium after treatment with Dilatel has been examined on 50 placentae of classified eutrophic premature and full-term births. In relation to the degree of damage to trophoblasts at the start of treatment and to dosage the response is mobilisation and further differentiation of Langhans cells and their transformation into mature plasmodium. The relevance of these results for metabolic transport and hormonal synthesis in the feto- maternal metabolic barrier and for the chance of therapeutic effects on insufficiency of the placenta is discussed.", "contents": "[The reaction of chorion epitheliums of human placentae to beta-sympathocomimetics (author's transl)]. The enzyme histochemical response of chorionic epithelium after treatment with Dilatel has been examined on 50 placentae of classified eutrophic premature and full-term births. In relation to the degree of damage to trophoblasts at the start of treatment and to dosage the response is mobilisation and further differentiation of Langhans cells and their transformation into mature plasmodium. The relevance of these results for metabolic transport and hormonal synthesis in the feto- maternal metabolic barrier and for the chance of therapeutic effects on insufficiency of the placenta is discussed."}
{"id": "PMID:4932", "title": "[PH-static pectin esterase analysis in sweet cherries (author's transl)].", "content": "For the analysis of pectin esterase (PE) activities in sweet cherries some methods, as described in literature, were tested as to their usefulness in this specific range of application. The PE activities in dependence of the methods of extraction, the pH-value and the temperature were examined and a suitable procedure was achieved. With this method the PE activities in deposited sweet cherries were analyzed.", "contents": "[PH-static pectin esterase analysis in sweet cherries (author's transl)]. For the analysis of pectin esterase (PE) activities in sweet cherries some methods, as described in literature, were tested as to their usefulness in this specific range of application. The PE activities in dependence of the methods of extraction, the pH-value and the temperature were examined and a suitable procedure was achieved. With this method the PE activities in deposited sweet cherries were analyzed."}
{"id": "PMID:4933", "title": "[Phospholipase D - a review (author's transl)].", "content": "Phospholipase D (phosphatidylcholine-phosphatidohydrolase, EC 3.1.4.4) hydrolyses lecithin into phosphatidic acid and choline. A review is given on the properties of phospholipase D described in the literature; it deals with the occurrence and distribution of phospholipase D in higher plants, with it's pH and temperature, substrate specifity, activators, inhibitors and with occurrence and properties of bacterial phospholipase D.", "contents": "[Phospholipase D - a review (author's transl)]. Phospholipase D (phosphatidylcholine-phosphatidohydrolase, EC 3.1.4.4) hydrolyses lecithin into phosphatidic acid and choline. A review is given on the properties of phospholipase D described in the literature; it deals with the occurrence and distribution of phospholipase D in higher plants, with it's pH and temperature, substrate specifity, activators, inhibitors and with occurrence and properties of bacterial phospholipase D."}
{"id": "PMID:4938", "title": "[Differential pharmacotherapy of neurotic conditions (comparative effectiveness of benzodiazepine derivatives)].", "content": "The effectiveness in treating borderline states to a certain degree depends upon the pole (sthenic or asthenic) of the corresponding disturbance. Tranquilizers are the preparations of choice in the treatment of disorders of an asthenic pole (psychopathy of the asthenic range, neurotic states). In borderline conditions of a sthenic pole the effectiveness of tranquilizers is equal or sometimes is even less than in therapy with small doses of neuroleptics. In treating neurotic conditions tranquilizers of the benzodiazepine group can be ranged in the following succession: nitrazepam, chlordiazepoxide, medazepam, oxazepam, diazepam, lorazepam. This preparation is a continuun of an increasing psychotropic activity.", "contents": "[Differential pharmacotherapy of neurotic conditions (comparative effectiveness of benzodiazepine derivatives)]. The effectiveness in treating borderline states to a certain degree depends upon the pole (sthenic or asthenic) of the corresponding disturbance. Tranquilizers are the preparations of choice in the treatment of disorders of an asthenic pole (psychopathy of the asthenic range, neurotic states). In borderline conditions of a sthenic pole the effectiveness of tranquilizers is equal or sometimes is even less than in therapy with small doses of neuroleptics. In treating neurotic conditions tranquilizers of the benzodiazepine group can be ranged in the following succession: nitrazepam, chlordiazepoxide, medazepam, oxazepam, diazepam, lorazepam. This preparation is a continuun of an increasing psychotropic activity."}
{"id": "PMID:4939", "title": "[The relationship between the state of the pulmonary circulation and indices of cerebral gas exchange in patients with acquired heart defects].", "content": "The author studied the state of hemeostasis in normals and in patients with acquired heart insufficiency. By means of bloody methods of triple probe samples of the blood inflow and outflow from the brain, and by biochemical methods they also studied 22 normals and 100 patients with acquired heart insufficiency for interrelations between the gas metabolism indices and acid-base equilibrium of the central pulmonary hemodynamics. As a results it was established that the brain blood flux in patients with acquired heart insufficiency in different degrees of pulmonary hypertension is adequate to the metabolic requirement of the brain in oxygen and corresponds to identical indices in normals. There was no relation between the state of pulmonary circulation and brain circulation.", "contents": "[The relationship between the state of the pulmonary circulation and indices of cerebral gas exchange in patients with acquired heart defects]. The author studied the state of hemeostasis in normals and in patients with acquired heart insufficiency. By means of bloody methods of triple probe samples of the blood inflow and outflow from the brain, and by biochemical methods they also studied 22 normals and 100 patients with acquired heart insufficiency for interrelations between the gas metabolism indices and acid-base equilibrium of the central pulmonary hemodynamics. As a results it was established that the brain blood flux in patients with acquired heart insufficiency in different degrees of pulmonary hypertension is adequate to the metabolic requirement of the brain in oxygen and corresponds to identical indices in normals. There was no relation between the state of pulmonary circulation and brain circulation."}
{"id": "PMID:4941", "title": "Effect of laser irradiation and immunosuppressive treatment on survival of mouse skin allotransplants.", "content": "The effect of laser beam on the survival of skin allotransplants has been studied. Irradiation of the donor skin and of the recipient graft bed improved the survival of the graft. The graft protecting effect of anti-thymocyte serum was considerably enhanced by laser irradiation.", "contents": "Effect of laser irradiation and immunosuppressive treatment on survival of mouse skin allotransplants. The effect of laser beam on the survival of skin allotransplants has been studied. Irradiation of the donor skin and of the recipient graft bed improved the survival of the graft. The graft protecting effect of anti-thymocyte serum was considerably enhanced by laser irradiation."}
{"id": "PMID:4947", "title": "Anesthesia for cesarean section III: effects of epidural analgesia on the respiratory adaptation of the newborn in elective cesarean section.", "content": "A rise in fetal Paco2 was observed after elective cesarean section in patients anesthetized both with a barbiturate and with nitrous oxide/oxygen. Epidural analgesia seemed to be a good alternative in order to attain better blood gas values in the newborn infant. Fourteen healthy mothers and their infants were studied in connection with elective cesarean section. Epidural analgesia with plain bupivacaine 0.75% was used. Doses varied between 90 and 120 mg. The time between the epidural injection and delivery was around 50 min. In six cases the fetal heart rate was registered continuously. Most of the mothers were sedated with diazepam intravenously or fully anesthetized, after delivery. The mothers were interviewed later. The respiratory adaptation of the infants was studied by blood gas and acid-base measurements in repeated arterial samples during the first 3 hours of life. A comparison was made with a group previously studied, where general anesthesia with a barbiturate, nitrous oxide/oxygen was the method used. The present material showed no differences concerning Pao2 and Paco2 but clearly indicated a tendency towards an earlier normalization of the initial metabolic acidosis. Mothers showed a respiratory alkalosis which was overcompensated by the metabolic component. Maternal blood pressure falls were observed in four cases, and fetal effects could be detected. Although epidural analgesia has a more favorable effect upon the newborn's metabolic component, both the compared methods allow good respiratory adaptation provided they are used correctly. Mothers can be given the opportunity to choose between being conscious or asleep when their child is delivered.", "contents": "Anesthesia for cesarean section III: effects of epidural analgesia on the respiratory adaptation of the newborn in elective cesarean section. A rise in fetal Paco2 was observed after elective cesarean section in patients anesthetized both with a barbiturate and with nitrous oxide/oxygen. Epidural analgesia seemed to be a good alternative in order to attain better blood gas values in the newborn infant. Fourteen healthy mothers and their infants were studied in connection with elective cesarean section. Epidural analgesia with plain bupivacaine 0.75% was used. Doses varied between 90 and 120 mg. The time between the epidural injection and delivery was around 50 min. In six cases the fetal heart rate was registered continuously. Most of the mothers were sedated with diazepam intravenously or fully anesthetized, after delivery. The mothers were interviewed later. The respiratory adaptation of the infants was studied by blood gas and acid-base measurements in repeated arterial samples during the first 3 hours of life. A comparison was made with a group previously studied, where general anesthesia with a barbiturate, nitrous oxide/oxygen was the method used. The present material showed no differences concerning Pao2 and Paco2 but clearly indicated a tendency towards an earlier normalization of the initial metabolic acidosis. Mothers showed a respiratory alkalosis which was overcompensated by the metabolic component. Maternal blood pressure falls were observed in four cases, and fetal effects could be detected. Although epidural analgesia has a more favorable effect upon the newborn's metabolic component, both the compared methods allow good respiratory adaptation provided they are used correctly. Mothers can be given the opportunity to choose between being conscious or asleep when their child is delivered."}
{"id": "PMID:4948", "title": "The effect of halothane anaesthesia upon cerebral oxygen consumption in the rat.", "content": "The influence of halothane (0.6 and 2%) upon cerebral (cortical) blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in artificially ventilated rats, using a modified technique of Kety & Schmidt (1948). The values obtained in halothane anaesthesia were compared to those recorded in nitrous oxide anaesthesia, or to those measured in unanesthetized animals given an analgesic drug (fentanyl citrate). Although it could be confirmed that halothane induces vasodilatation in the brain, there were relatively small differences in CBF between the groups. The results demonstrate that, in the rat, halothane depresses CMRo2 in a dose-dependent way. With 0.6% halothane, CMRo2 was reduced by 20-30% and, with 2% halothane, CMRo2 was reduced by about 50%. Thus, in the rat the effect of 2% halothane upon metabolic rate is comparable to that observed in barbiturate anaesthesia.", "contents": "The effect of halothane anaesthesia upon cerebral oxygen consumption in the rat. The influence of halothane (0.6 and 2%) upon cerebral (cortical) blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in artificially ventilated rats, using a modified technique of Kety & Schmidt (1948). The values obtained in halothane anaesthesia were compared to those recorded in nitrous oxide anaesthesia, or to those measured in unanesthetized animals given an analgesic drug (fentanyl citrate). Although it could be confirmed that halothane induces vasodilatation in the brain, there were relatively small differences in CBF between the groups. The results demonstrate that, in the rat, halothane depresses CMRo2 in a dose-dependent way. With 0.6% halothane, CMRo2 was reduced by 20-30% and, with 2% halothane, CMRo2 was reduced by about 50%. Thus, in the rat the effect of 2% halothane upon metabolic rate is comparable to that observed in barbiturate anaesthesia."}
{"id": "PMID:4950", "title": "Treatment of comatose patients by mechanical hyperventilation.", "content": "In case of cranial trauma, early respiratory troubles either of central or peripheral origin often accelerate the deterioration of the neurological situation. The different values of PCO2, PO2, pH and alcaline reserve measured on samples of CSF in comatose patients prove the central acidosis related to metabolic and vascular disorders in the damaged areas. Our results confirm the correlation between the importance of this disturbances and the severity of the trauma. It is thus necessary to insure patients of satisfactory respiration conditions. The tracheobronchial cleansing is applicable to intubated or tracheotomized patients by an instillation of 5ml of simple or bicarbonated physiological serum 4 to 6 times a day, followed by repeated aspirations and associated to a preventive endotracheal instillation of 80 mg of Gentamycin 4 times a day. Moreover we use controlled respiration which does not modify the gazometric parameters in the CSF but which assures patients a normoxia and moderate hypocapnia with a decrease of intracranial hypertension. Treatment by controlled hyperventilation must be precocious, because the recuperation at the level of the damaged zones is very slow.", "contents": "Treatment of comatose patients by mechanical hyperventilation. In case of cranial trauma, early respiratory troubles either of central or peripheral origin often accelerate the deterioration of the neurological situation. The different values of PCO2, PO2, pH and alcaline reserve measured on samples of CSF in comatose patients prove the central acidosis related to metabolic and vascular disorders in the damaged areas. Our results confirm the correlation between the importance of this disturbances and the severity of the trauma. It is thus necessary to insure patients of satisfactory respiration conditions. The tracheobronchial cleansing is applicable to intubated or tracheotomized patients by an instillation of 5ml of simple or bicarbonated physiological serum 4 to 6 times a day, followed by repeated aspirations and associated to a preventive endotracheal instillation of 80 mg of Gentamycin 4 times a day. Moreover we use controlled respiration which does not modify the gazometric parameters in the CSF but which assures patients a normoxia and moderate hypocapnia with a decrease of intracranial hypertension. Treatment by controlled hyperventilation must be precocious, because the recuperation at the level of the damaged zones is very slow."}
{"id": "PMID:4952", "title": "Resistant transitory epilepsy in children.", "content": "Three case histories are presented which are characterized by progressive, severe symptoms of mental and epileptic nature with EEG abnormalities of increasing severity culminating in \"hypsarhythmia\". The seizures were resistant to any treatment over a period of several months. Apparently spontaneous cures followed, and the patients remained healthy during follow-up, which ranged from 10 to 12 years. The observations confirm Lennox's remark that a miraculous cure may occasionally be expected in even severe, probably symptomatic, epilepsy. Some exogenous (infectious?) cause is suspected.", "contents": "Resistant transitory epilepsy in children. Three case histories are presented which are characterized by progressive, severe symptoms of mental and epileptic nature with EEG abnormalities of increasing severity culminating in \"hypsarhythmia\". The seizures were resistant to any treatment over a period of several months. Apparently spontaneous cures followed, and the patients remained healthy during follow-up, which ranged from 10 to 12 years. The observations confirm Lennox's remark that a miraculous cure may occasionally be expected in even severe, probably symptomatic, epilepsy. Some exogenous (infectious?) cause is suspected."}
{"id": "PMID:4951", "title": "A comparison of the cardiovascular effects of enflurane, halothane, methoxyflurane and fluroxene during open cardiac surgery.", "content": "During open heart surgery hemodynamic changes due to 1.5% enflurane, 0.75% halothane, 0.18% methoxyflurane and 3.4% fluroxene have been compared. The following parameters have been measured: arterial pressure, heart rate, cardiac output, right and left atrial pressure, left ventricular pressure and dp/dt. The strongest effects were found with enflurane and halothane. Marked reduction in cardiac index, stroke index, left ventricular dp/dt as well as reduction of peripheral resistance caused severe systemic hypotension. Because of its slow uptake methoxyflurane was followed by small hemodynamic changes in this study. The rapid acting fluroxene had caused only minor reductions of cardiac output, stroke volume and dp/dt. There was no decrease in peripheral resistance.", "contents": "A comparison of the cardiovascular effects of enflurane, halothane, methoxyflurane and fluroxene during open cardiac surgery. During open heart surgery hemodynamic changes due to 1.5% enflurane, 0.75% halothane, 0.18% methoxyflurane and 3.4% fluroxene have been compared. The following parameters have been measured: arterial pressure, heart rate, cardiac output, right and left atrial pressure, left ventricular pressure and dp/dt. The strongest effects were found with enflurane and halothane. Marked reduction in cardiac index, stroke index, left ventricular dp/dt as well as reduction of peripheral resistance caused severe systemic hypotension. Because of its slow uptake methoxyflurane was followed by small hemodynamic changes in this study. The rapid acting fluroxene had caused only minor reductions of cardiac output, stroke volume and dp/dt. There was no decrease in peripheral resistance."}
{"id": "PMID:4956", "title": "Long-term hypotensive effect of atenolol (ICI 66.082), a new beta-adrenergic blocking agent.", "content": "A report is given from an on-going multicenter trial in Sweden, in which 117 hypertensive patients have been treated with a new cardioselective beta-adrenergic blocking agent, atenolol (ICI 66.082, Tenormin) for an average of six months (range 2-21). Statistically significant reductions of BP were observed, recumbent by 29/19 mmHg (p less than 0.0001) and standing by 28/18 mmHg (p less than 0.0001). Few and comparatively mild side-effects were seen.", "contents": "Long-term hypotensive effect of atenolol (ICI 66.082), a new beta-adrenergic blocking agent. A report is given from an on-going multicenter trial in Sweden, in which 117 hypertensive patients have been treated with a new cardioselective beta-adrenergic blocking agent, atenolol (ICI 66.082, Tenormin) for an average of six months (range 2-21). Statistically significant reductions of BP were observed, recumbent by 29/19 mmHg (p less than 0.0001) and standing by 28/18 mmHg (p less than 0.0001). Few and comparatively mild side-effects were seen."}
{"id": "PMID:4953", "title": "Bacteremia after tonsillectomy and adenectomy.", "content": "40% of negative hemocultures become positive immediately after tonsillectomies and/or adenectomies. This bacteremia is asymptomatic and remains no longer than one hour.", "contents": "Bacteremia after tonsillectomy and adenectomy. 40% of negative hemocultures become positive immediately after tonsillectomies and/or adenectomies. This bacteremia is asymptomatic and remains no longer than one hour."}
{"id": "PMID:4957", "title": "Hemodynamic long-term effects of timolol at rest and during exercise in essential hypertension.", "content": "Sixteen men with previously untreated essential hypertension in WHO stage I have been studied as out-patients. Oxygen consumption, heart rate (HR), cardiac output (Q) (Cardiogreen) and intraarterial brachial pressure were recorded at rest in supine and sitting position and during steady state work at 300, 600 and 900 kpm/min. The subjects were treated with timolol as the sole drug for one year and the hemodynamic study was repeated. BP was reduced approximately 18% at rest and 14% during exercise, HR approximately 26% and the cardiac index 28% at rest supine and 32% at rest sitting. During exercise the reductions in Q were 25-30%. The calculated total peripheral resistance was significantly increased at rest as well as during exercise. The product of mean arterial pressure and HR was reduced about 40%. No severe side-effects were seen.", "contents": "Hemodynamic long-term effects of timolol at rest and during exercise in essential hypertension. Sixteen men with previously untreated essential hypertension in WHO stage I have been studied as out-patients. Oxygen consumption, heart rate (HR), cardiac output (Q) (Cardiogreen) and intraarterial brachial pressure were recorded at rest in supine and sitting position and during steady state work at 300, 600 and 900 kpm/min. The subjects were treated with timolol as the sole drug for one year and the hemodynamic study was repeated. BP was reduced approximately 18% at rest and 14% during exercise, HR approximately 26% and the cardiac index 28% at rest supine and 32% at rest sitting. During exercise the reductions in Q were 25-30%. The calculated total peripheral resistance was significantly increased at rest as well as during exercise. The product of mean arterial pressure and HR was reduced about 40%. No severe side-effects were seen."}
{"id": "PMID:4958", "title": "[Energy state of the cerebral cortex of the cat during hyperventilation (author's transl)].", "content": "Average Po2 and Pco2, local blood flow and pH values in the cerebral cortex of the cat were measured during passive hyperventilation (arterial Pco2 below 19 mm Hg). At defined intervals tissue samples were taken for metabolite analysis. The object of the study was to correlate the data obtained on the brain surface with metabolic responses. Immediately after the start of hyperventilation blood flow decreased, average cortical tissue pressures of O2 and CO2 fell, and there was a simultaneous rise in cortical pH. At a later stage in the experiment the local blood supply reverted to its resting level. Despite a fivefold rise in tissue lactate level during hyperventilation and a decrease in local O2 pressure on the brain surface to 5-10 mm Hg the degree of phosphorylation of energy rich phosphates was not less than under normal conditions of oxygenation. Our investigations showed no evidence of energy lack in cerebral cortex cells during hyperventilation. Cellular hypoxia and its characteristics are defined. The possible causes of raised tissue lactate levels during hyperventilation despite the lack of evidence of cellular hypoxia are discussed.", "contents": "[Energy state of the cerebral cortex of the cat during hyperventilation (author's transl)]. Average Po2 and Pco2, local blood flow and pH values in the cerebral cortex of the cat were measured during passive hyperventilation (arterial Pco2 below 19 mm Hg). At defined intervals tissue samples were taken for metabolite analysis. The object of the study was to correlate the data obtained on the brain surface with metabolic responses. Immediately after the start of hyperventilation blood flow decreased, average cortical tissue pressures of O2 and CO2 fell, and there was a simultaneous rise in cortical pH. At a later stage in the experiment the local blood supply reverted to its resting level. Despite a fivefold rise in tissue lactate level during hyperventilation and a decrease in local O2 pressure on the brain surface to 5-10 mm Hg the degree of phosphorylation of energy rich phosphates was not less than under normal conditions of oxygenation. Our investigations showed no evidence of energy lack in cerebral cortex cells during hyperventilation. Cellular hypoxia and its characteristics are defined. The possible causes of raised tissue lactate levels during hyperventilation despite the lack of evidence of cellular hypoxia are discussed."}
{"id": "PMID:4959", "title": "[Postoperative mental blocking in a continuous reaction task. With supplementary results showing the influence of age (author's transl)].", "content": "By means of a four colour device for measuring continuous reaction sequences the mental blockings of brain damaged patients in comparison with patients suffering from skin disease were determined. Differences due to age were also investigated. The analysis of frequency distribution of reaction times (dissection method according to Daeves and Beckel) yielded the following results: a) Brain damaged patients show a higher percentage of blockings (23%) than patients suffering from skin-disease (10%). \"Normal\" reaction times as well as \"blockings\" are not prolonged significantly. b) Older patients show prolonged normal reaction times and prolonged blockings without increase in the percentage of blockings. c) Patients with left hemisphere lesions show longer normal reaction times than those who undergo right hemisphere operations. The results are discussed with regard to their significance for theory and practice (road accidents).", "contents": "[Postoperative mental blocking in a continuous reaction task. With supplementary results showing the influence of age (author's transl)]. By means of a four colour device for measuring continuous reaction sequences the mental blockings of brain damaged patients in comparison with patients suffering from skin disease were determined. Differences due to age were also investigated. The analysis of frequency distribution of reaction times (dissection method according to Daeves and Beckel) yielded the following results: a) Brain damaged patients show a higher percentage of blockings (23%) than patients suffering from skin-disease (10%). \"Normal\" reaction times as well as \"blockings\" are not prolonged significantly. b) Older patients show prolonged normal reaction times and prolonged blockings without increase in the percentage of blockings. c) Patients with left hemisphere lesions show longer normal reaction times than those who undergo right hemisphere operations. The results are discussed with regard to their significance for theory and practice (road accidents)."}
{"id": "PMID:4963", "title": "Immunosuppression by fetal liver as a model for tolerance to self.", "content": "The embryonic liver chimera system was used as a model to study the development of tolerance to self antigens. It was found that the permanent tolerant state which was induced in (C3H/eb x C57BL/6)F1 irradiated hosts following reconstitution with parental C57BL liver cells could be due to the development of suppressor cells within the liver cell inoculum, which specifically prevent reactivity of immunocompetent cells. General suppressor activity could be found in embryonic liver cells at early stages of gestation. However, the differentiation of such cells into specific suppressor of \"self\" antigens is dependent on the presence of the thymus.", "contents": "Immunosuppression by fetal liver as a model for tolerance to self. The embryonic liver chimera system was used as a model to study the development of tolerance to self antigens. It was found that the permanent tolerant state which was induced in (C3H/eb x C57BL/6)F1 irradiated hosts following reconstitution with parental C57BL liver cells could be due to the development of suppressor cells within the liver cell inoculum, which specifically prevent reactivity of immunocompetent cells. General suppressor activity could be found in embryonic liver cells at early stages of gestation. However, the differentiation of such cells into specific suppressor of \"self\" antigens is dependent on the presence of the thymus."}
{"id": "PMID:4964", "title": "Suppressor cells in the embryonic thymus mediate allograft tolerance.", "content": "Thymus cells from non-immunized young chickens suppress the allograft rejection in lightly irradiated syngeneic or allogeneic recipients and mediate longlasting skingraft survival in a significant proportion of recipients across a strong histocompatibility difference. Suppressive activity of this kind is already found in the embryonic thymus and is therefore believed to mediate also self tolerance and neonatal allograft tolerance.", "contents": "Suppressor cells in the embryonic thymus mediate allograft tolerance. Thymus cells from non-immunized young chickens suppress the allograft rejection in lightly irradiated syngeneic or allogeneic recipients and mediate longlasting skingraft survival in a significant proportion of recipients across a strong histocompatibility difference. Suppressive activity of this kind is already found in the embryonic thymus and is therefore believed to mediate also self tolerance and neonatal allograft tolerance."}
{"id": "PMID:4970", "title": "Internal mammary artery bypass graft in reoperative myocardioal revascularization.", "content": "Thirty-two consecutive patients who earlier received indirect or direct myocardial revascularization underwent reoperation with one or more internal mammary artery grafts either alone or in combination with saphenous vein grafts. The main indication for reoperation was graft closure or progression of coronary atherosclerosis in nongrafted vessels, or both. Graft construction was performed under normothermic perfusion and anoxic arrest with interrupted suture technique. No intraoperative infarctions or hospital deaths occurred. All patients are alive after an average follow-up period of 20 months, and two thirds are asymptomatic. Arteriography after reoperation in nine patients revealed patency of eight of nine internal mammary artery and five of five secondary vein grafts. When angiographic and symptomatic indications for reoperation exist, the internal mammary artery bypass graft has become a valuable alternative, particularly for patients with small coronary vessels or previous vein graft failure.", "contents": "Internal mammary artery bypass graft in reoperative myocardioal revascularization. Thirty-two consecutive patients who earlier received indirect or direct myocardial revascularization underwent reoperation with one or more internal mammary artery grafts either alone or in combination with saphenous vein grafts. The main indication for reoperation was graft closure or progression of coronary atherosclerosis in nongrafted vessels, or both. Graft construction was performed under normothermic perfusion and anoxic arrest with interrupted suture technique. No intraoperative infarctions or hospital deaths occurred. All patients are alive after an average follow-up period of 20 months, and two thirds are asymptomatic. Arteriography after reoperation in nine patients revealed patency of eight of nine internal mammary artery and five of five secondary vein grafts. When angiographic and symptomatic indications for reoperation exist, the internal mammary artery bypass graft has become a valuable alternative, particularly for patients with small coronary vessels or previous vein graft failure."}
{"id": "PMID:4972", "title": "Evaluation of a 5-mum stainless steel filter as an intravenous inline filter or prefilter.", "content": "The suitability of a 5-mum stainless steel filter as an inline filter or a protective prefilter during simulated i.v. therapy was evaluated using flow rate measurements of two routinely used i.v. fluids and parenteral nutrition fluid. As an inline i.v. filter, the 5-mum stainless steel filter was capable of maintaining suitable flow rates. The addition of antibiotic additives decreased the flow rates slightly but not below the range required for i.v. therapy. Flow rate profiles, however, when compared to a 0.45-mum membrane filter suggest that antibiotic additives contain high numbers of particles in the less than 5-mum range. Consequently many of the particles, especially those in the less than 3-mum range will pass the 5-mum filter. As a protective prefilter, the 5-mum filter device in combination with a 0.45-mum membrane filter provided more uniform flow rates over longer periods of time when additives were employed. Using the aspiration device as a prefilter for adding antibiotics to the infusion fluid resulted in improved flow rates through a 0.45-mum membrane filter for lactated Ringer's containing cephalothin sodium, while for solutions containing ampicillin or oxytetracycline, prefilteration did not change the flow rate profiles.", "contents": "Evaluation of a 5-mum stainless steel filter as an intravenous inline filter or prefilter. The suitability of a 5-mum stainless steel filter as an inline filter or a protective prefilter during simulated i.v. therapy was evaluated using flow rate measurements of two routinely used i.v. fluids and parenteral nutrition fluid. As an inline i.v. filter, the 5-mum stainless steel filter was capable of maintaining suitable flow rates. The addition of antibiotic additives decreased the flow rates slightly but not below the range required for i.v. therapy. Flow rate profiles, however, when compared to a 0.45-mum membrane filter suggest that antibiotic additives contain high numbers of particles in the less than 5-mum range. Consequently many of the particles, especially those in the less than 3-mum range will pass the 5-mum filter. As a protective prefilter, the 5-mum filter device in combination with a 0.45-mum membrane filter provided more uniform flow rates over longer periods of time when additives were employed. Using the aspiration device as a prefilter for adding antibiotics to the infusion fluid resulted in improved flow rates through a 0.45-mum membrane filter for lactated Ringer's containing cephalothin sodium, while for solutions containing ampicillin or oxytetracycline, prefilteration did not change the flow rate profiles."}
{"id": "PMID:4973", "title": "Hyperactive children and the efficacy of psychoactive drugs as a treatment intervention.", "content": "Characteristics of hyperactive children, including speculation in regard to etiology, are reviewed. Drug effects studies and drug treatment of hyperactive behavior are examined, and unresolved issues are discussed. Conclusions indicate that individual differences in hyperative children should form the basis for treatment planning, rather than simply treating groups of children under the rubric \"hyperactivity.\"", "contents": "Hyperactive children and the efficacy of psychoactive drugs as a treatment intervention. Characteristics of hyperactive children, including speculation in regard to etiology, are reviewed. Drug effects studies and drug treatment of hyperactive behavior are examined, and unresolved issues are discussed. Conclusions indicate that individual differences in hyperative children should form the basis for treatment planning, rather than simply treating groups of children under the rubric \"hyperactivity.\""}
{"id": "PMID:4969", "title": "Experiments on the role of virus infections in the pathogenesis of bronchial asthma. The role of innate or acquired insufficiency or ergotropic adaptation in the mechanism of genesis of bronchial asthma.", "content": "The wide mosaic of congruent clinical and experimental observations led to the postulation that the cause of the pharmacological abnormality of the asthmatic patient, i.e. the immensely increased reactivity of the bronchial smooth muscles, is to be sought in an insufficiency of the beta-adrenergic receptor system. It is to be assumed that the so-called asthma diatheses is based inter alia on a genetically determined defect of the adenyl cyclase system. The role of previous infections of the respiratory tract in asthmagenesis should lie--following this working theory--not in a sensitization in the sense of an allergic reaction of the immediate type, but in the formation of a defective beta-adrenergic substance or in a blockade of the beta-receptor. A genetically determined innate defect of the beta-adrenergic receptors, or a defect acquired through infections of the respiratory tract, is hence likely to be the cause of the pathologically potentiated reactivity of the bronchia. It is likely that the infective stimuli--quite apart from this preparatory role--are later capable of triggering asthmatic paroxysms when the vegetative homeostasis is impaired. We know from the experiments of many authors that a blockade of the beta-receptors produced by chemical blocker substances, or by pertussis vaccine or various bacterial substances, results in a significant increase in bronchial reactivity towards histamine, serotonin, acetylcholine and other stimuli. We have shown in our experiments that heat-inactivated adeno viruses and influenza viruses also increase the anaphylactic shock reactivity and the histamine reactivity of the organism. On the basis of this working hypothesis, the pathomechanism of the asthmatic process is as follows in individual asthma forms: 1) In the 'purely\" allergic asthma form, the antigen-antibody reaction that occurs after sensitization (i.e. formation of skin-sensitizing allergic antibodies of the class IgE) results in re-formation and release of slow-reacting-substances. spasm of the bronchial muscles, asthmatic paroxysm. The expulsion of catecholamines that follows the release of slow-reacting-substances makes a decisive contribution to the reestablishment of the impaired homeostatic balance. It is to be assumed that this form of asthma both symptomatically and causally--using specific desensitization--can be influenced more easily than other forms of asthma with a more complicated pathogenic background. 2) In the second allergically determined form of asthma, we are confronted by the genetically fixed or acquired insufficiency of the beta-receptors in addition to the immunological mechanism. As a result of the innate or acquired blockade of the beta-receptive substance, or the relative dominance of the alpha-receptors, the catecholamines (that physiologically serve to maintain homeostasis) contribute to a protraction, intensification and perpetuation of the bronchial obstruction. In this way the asthmatic circulus vitiosus is complete...", "contents": "Experiments on the role of virus infections in the pathogenesis of bronchial asthma. The role of innate or acquired insufficiency or ergotropic adaptation in the mechanism of genesis of bronchial asthma. The wide mosaic of congruent clinical and experimental observations led to the postulation that the cause of the pharmacological abnormality of the asthmatic patient, i.e. the immensely increased reactivity of the bronchial smooth muscles, is to be sought in an insufficiency of the beta-adrenergic receptor system. It is to be assumed that the so-called asthma diatheses is based inter alia on a genetically determined defect of the adenyl cyclase system. The role of previous infections of the respiratory tract in asthmagenesis should lie--following this working theory--not in a sensitization in the sense of an allergic reaction of the immediate type, but in the formation of a defective beta-adrenergic substance or in a blockade of the beta-receptor. A genetically determined innate defect of the beta-adrenergic receptors, or a defect acquired through infections of the respiratory tract, is hence likely to be the cause of the pathologically potentiated reactivity of the bronchia. It is likely that the infective stimuli--quite apart from this preparatory role--are later capable of triggering asthmatic paroxysms when the vegetative homeostasis is impaired. We know from the experiments of many authors that a blockade of the beta-receptors produced by chemical blocker substances, or by pertussis vaccine or various bacterial substances, results in a significant increase in bronchial reactivity towards histamine, serotonin, acetylcholine and other stimuli. We have shown in our experiments that heat-inactivated adeno viruses and influenza viruses also increase the anaphylactic shock reactivity and the histamine reactivity of the organism. On the basis of this working hypothesis, the pathomechanism of the asthmatic process is as follows in individual asthma forms: 1) In the 'purely\" allergic asthma form, the antigen-antibody reaction that occurs after sensitization (i.e. formation of skin-sensitizing allergic antibodies of the class IgE) results in re-formation and release of slow-reacting-substances. spasm of the bronchial muscles, asthmatic paroxysm. The expulsion of catecholamines that follows the release of slow-reacting-substances makes a decisive contribution to the reestablishment of the impaired homeostatic balance. It is to be assumed that this form of asthma both symptomatically and causally--using specific desensitization--can be influenced more easily than other forms of asthma with a more complicated pathogenic background. 2) In the second allergically determined form of asthma, we are confronted by the genetically fixed or acquired insufficiency of the beta-receptors in addition to the immunological mechanism. As a result of the innate or acquired blockade of the beta-receptive substance, or the relative dominance of the alpha-receptors, the catecholamines (that physiologically serve to maintain homeostasis) contribute to a protraction, intensification and perpetuation of the bronchial obstruction. In this way the asthmatic circulus vitiosus is complete..."}
{"id": "PMID:4974", "title": "Ventilatory response to hypercapnia in the larger spotted dogfish Scyliorhinus stellaris.", "content": "Dogfish were exposed to sudden changes of Pco2 in inspired seawater. During hypercapnia breathing frequency remained constant, but gill ventilation was transiently increased to about 140% of control levels in the 1st h. O2 uptake was significantly increased also, but returned to the initial level before nomalization of gill ventilation. In contrast to the transient rise in gill ventilation and O2 uptake, arterial Po2 was increased for the whole period of hypercapnia. Hypercapnia results in a marked fall in pHa which returned to the initial value in 4-5 h even though hypercapnia is maintained. This rise in pHa with little change in PaCO2 was associated with an increase in plasma bicarbonate concentration. The increase of plasma bicarbonate was in part due to compensatory bicarbonate uptake from the seawater across the gills and in part was effected by transfer between intracellular tissue compartments and extracellular spaces. The compensatory bicarbonate exchange mechanism in the gills seems to have a delay both after onset and termination of hypercapnia.", "contents": "Ventilatory response to hypercapnia in the larger spotted dogfish Scyliorhinus stellaris. Dogfish were exposed to sudden changes of Pco2 in inspired seawater. During hypercapnia breathing frequency remained constant, but gill ventilation was transiently increased to about 140% of control levels in the 1st h. O2 uptake was significantly increased also, but returned to the initial level before nomalization of gill ventilation. In contrast to the transient rise in gill ventilation and O2 uptake, arterial Po2 was increased for the whole period of hypercapnia. Hypercapnia results in a marked fall in pHa which returned to the initial value in 4-5 h even though hypercapnia is maintained. This rise in pHa with little change in PaCO2 was associated with an increase in plasma bicarbonate concentration. The increase of plasma bicarbonate was in part due to compensatory bicarbonate uptake from the seawater across the gills and in part was effected by transfer between intracellular tissue compartments and extracellular spaces. The compensatory bicarbonate exchange mechanism in the gills seems to have a delay both after onset and termination of hypercapnia."}
{"id": "PMID:4975", "title": "Does hyperinsulinemia in ob/ob mice cause an insulin-stimulated adipose tissue?", "content": "After a 1-h preincubation to remove endogenous insulin, adipose tissue of obese mice (C57BL/L4 ob/ob) had a lower rate of glucose metabolism than tissue which was not preincubated. In contrast, preincubation did not change the metabolism of adipose tissue from lean mice (C57B1/6J +/+). The preincubation effect was abolished in obese mice which had had their serum insulin levels lowered toward normal by streptozotocin treatment. Injection of anti-insulin serum to obese mice caused adipose tissue removed 15 min after the injection to display a rate of glucose metabolsim lower than that of tissue removed before the injection. No such effect was seen in lean mice. These data are consistent with the hypothesis that hyperinsulinemia in the obese mice causes a chronic state of insulin stimulation of their adipose tissue, possibly contributing to their high rates of lipogenesis and their obesity. Several lipogenic enzymes were measured in adipose tissue of both lean and obese mice, and no single enzymatic abnormality was detected which might explain the hyperlipogenesis. Pyruvate dehydrogenase and acetyl-CoA carboxylase were both insulin-sensitive enzymes in lean and obese mice.", "contents": "Does hyperinsulinemia in ob/ob mice cause an insulin-stimulated adipose tissue? After a 1-h preincubation to remove endogenous insulin, adipose tissue of obese mice (C57BL/L4 ob/ob) had a lower rate of glucose metabolism than tissue which was not preincubated. In contrast, preincubation did not change the metabolism of adipose tissue from lean mice (C57B1/6J +/+). The preincubation effect was abolished in obese mice which had had their serum insulin levels lowered toward normal by streptozotocin treatment. Injection of anti-insulin serum to obese mice caused adipose tissue removed 15 min after the injection to display a rate of glucose metabolsim lower than that of tissue removed before the injection. No such effect was seen in lean mice. These data are consistent with the hypothesis that hyperinsulinemia in the obese mice causes a chronic state of insulin stimulation of their adipose tissue, possibly contributing to their high rates of lipogenesis and their obesity. Several lipogenic enzymes were measured in adipose tissue of both lean and obese mice, and no single enzymatic abnormality was detected which might explain the hyperlipogenesis. Pyruvate dehydrogenase and acetyl-CoA carboxylase were both insulin-sensitive enzymes in lean and obese mice."}
{"id": "PMID:4976", "title": "Importance of pulmonary ventilation in respiratory control in the bullfrog.", "content": "Pulmonary and cutaneous O2 consumption (Vo2) and CO2 production (Vco2) were measured simultaneously in bullfrogs Rana catesbeiana at 20 degrees C. The lungs were responsible for 77.3-91.0% of the total Vo2 and 28.5-74.9% of the total VCO2. The distribution of the total exchange between the lungs and skin depended on metabolic rate; frogs with higher rates relied more heavily on the pulmonary mode for both Vo2 and Vco2. When prevented from ventilating their lungs in an O2-rich environment, bullfrogs developed severe respiratory acidosis, demonstrating the importance of lung exchange in normal acid-base balance. When frogs were totally submerged in an O2-saturated medium, skin Vco2 increased linearly to a steady-state value which approximated the preapneic total Vco2. In these same animals, arterial Pco2 increased proportionately to the increase in skin Vco2, indicating that skin diffusion capacity for CO2 was unaffected. We conclude that the control of breathing in the bullfrog in response to changes in metabolic rate relies predominantly on changes in lung ventilation while the skin plays a more passive role.", "contents": "Importance of pulmonary ventilation in respiratory control in the bullfrog. Pulmonary and cutaneous O2 consumption (Vo2) and CO2 production (Vco2) were measured simultaneously in bullfrogs Rana catesbeiana at 20 degrees C. The lungs were responsible for 77.3-91.0% of the total Vo2 and 28.5-74.9% of the total VCO2. The distribution of the total exchange between the lungs and skin depended on metabolic rate; frogs with higher rates relied more heavily on the pulmonary mode for both Vo2 and Vco2. When prevented from ventilating their lungs in an O2-rich environment, bullfrogs developed severe respiratory acidosis, demonstrating the importance of lung exchange in normal acid-base balance. When frogs were totally submerged in an O2-saturated medium, skin Vco2 increased linearly to a steady-state value which approximated the preapneic total Vco2. In these same animals, arterial Pco2 increased proportionately to the increase in skin Vco2, indicating that skin diffusion capacity for CO2 was unaffected. We conclude that the control of breathing in the bullfrog in response to changes in metabolic rate relies predominantly on changes in lung ventilation while the skin plays a more passive role."}
{"id": "PMID:4977", "title": "Electromyographic response of respiratory muscles during elastic loading.", "content": "The response of respiratory motor neurons to graded elastic loading was assessed in anesthetized dogs by recording the electromyogram (EMG) from the diaphragm (ED) and the intercostal muscle (EIC). Elastic loads were applied for 1-20 breaths. The effects of changes in PCO2 on respiratory motor neuron output was assessed by applying loads during the course of CO2 rebreathing. On the first loaded breath, ED and EIC increased reflexly due chiefly to prolongation of inspiration. Vagotomy or vagal cooling to block the Hering-Breuer reflex eliminated the increase in ED and diminished the increase in EIC. During the second to fifth breath, the level of EMG activity was disproportionately high for the level of PCO2, suggesting an additional reflex component over and above the reflex activity present on the first loaded breath.", "contents": "Electromyographic response of respiratory muscles during elastic loading. The response of respiratory motor neurons to graded elastic loading was assessed in anesthetized dogs by recording the electromyogram (EMG) from the diaphragm (ED) and the intercostal muscle (EIC). Elastic loads were applied for 1-20 breaths. The effects of changes in PCO2 on respiratory motor neuron output was assessed by applying loads during the course of CO2 rebreathing. On the first loaded breath, ED and EIC increased reflexly due chiefly to prolongation of inspiration. Vagotomy or vagal cooling to block the Hering-Breuer reflex eliminated the increase in ED and diminished the increase in EIC. During the second to fifth breath, the level of EMG activity was disproportionately high for the level of PCO2, suggesting an additional reflex component over and above the reflex activity present on the first loaded breath."}
{"id": "PMID:4978", "title": "Plasma secretin and gastrin responses to a meat meal and duodenal acidification in dogs.", "content": "In five conscious dogs with gastric fistula and two duodenal cannulas, plasma RIA secretin and gastrin levels were determined in response to 1) infusion of 0.1 N HCl in the proximal duodenal cannula, 2) ingestion of a meal, and 3) intraduodenal infusion of 0.1 N HCl following ingestion of a meal. Significant increases in plasma RIA secretin levels occurred during duodenal acidification. However, no significant change occurred in the secretin levels after ingestion of a meal, whereas significant increase in plasma gastrin level was observed. Postprandial duodenal pH remained above 4.5 for 3 h.", "contents": "Plasma secretin and gastrin responses to a meat meal and duodenal acidification in dogs. In five conscious dogs with gastric fistula and two duodenal cannulas, plasma RIA secretin and gastrin levels were determined in response to 1) infusion of 0.1 N HCl in the proximal duodenal cannula, 2) ingestion of a meal, and 3) intraduodenal infusion of 0.1 N HCl following ingestion of a meal. Significant increases in plasma RIA secretin levels occurred during duodenal acidification. However, no significant change occurred in the secretin levels after ingestion of a meal, whereas significant increase in plasma gastrin level was observed. Postprandial duodenal pH remained above 4.5 for 3 h."}
{"id": "PMID:4979", "title": "Intracellular pH of brain: alterations in acute respiratory acidosis and alkalosis.", "content": "To evaluate the metabolic adaptations of the brain to acute respiratory acid-base disturbances, a method was developed to measure intracellular pH (pHi) in the brain of dogs under conditions in which arterial pH is rapidly altered. Brain pHi was determined by measuring the distribution of 14C-labeled dimethadione (DMO) in brain relative to cortical CSF. Brain extracellular space (ECS) was evaluated as the 35SO4 = space relative to cortical CSF, and arterial Po2 was maintained at 82-110 mmHg. In normal dogs, brain (cerebral cortex) pHi was 7.05, and after 1 h of hypercapnia (arterial pH = 7.07) it fell to 6.93. However, after 3 h with arterial Pco2 maintained at 85 mmHg brain pHi was normal (7.06), and during this time brain bicarbonate had risen from 11.3 to 24.4 meq/kg H2O. These changes were not prevented by intravenous doses of acetazolamide,", "contents": "Intracellular pH of brain: alterations in acute respiratory acidosis and alkalosis. To evaluate the metabolic adaptations of the brain to acute respiratory acid-base disturbances, a method was developed to measure intracellular pH (pHi) in the brain of dogs under conditions in which arterial pH is rapidly altered. Brain pHi was determined by measuring the distribution of 14C-labeled dimethadione (DMO) in brain relative to cortical CSF. Brain extracellular space (ECS) was evaluated as the 35SO4 = space relative to cortical CSF, and arterial Po2 was maintained at 82-110 mmHg. In normal dogs, brain (cerebral cortex) pHi was 7.05, and after 1 h of hypercapnia (arterial pH = 7.07) it fell to 6.93. However, after 3 h with arterial Pco2 maintained at 85 mmHg brain pHi was normal (7.06), and during this time brain bicarbonate had risen from 11.3 to 24.4 meq/kg H2O. These changes were not prevented by intravenous doses of acetazolamide,"}
{"id": "PMID:4980", "title": "Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions.", "content": "Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane  exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.", "contents": "Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions. Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane  exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell."}
{"id": "PMID:4981", "title": "Cardiovascular effects of cerebroventricular ouabain perfusion in the adult dog.", "content": "Cerebroventricular perfusion with artificial cerebrospinal fluid containing 10(-5) M ouabain was performed in adult dogs in order to describe the time course of the cardiovascular effect of intraventricular ouabain and to evaluate treatments to eliminate the cardiovascular effect. The central effect of ouabain caused a 56% increase in blood pressure above control values and a 35% increase in heart rate with various cardiac arrhythmias. Both alpha- and beta-adrenergic blocking drugs given intravenously.altered the pressure and rate effects ou ouabain, whereas vagotomy attenuated the effect.", "contents": "Cardiovascular effects of cerebroventricular ouabain perfusion in the adult dog. Cerebroventricular perfusion with artificial cerebrospinal fluid containing 10(-5) M ouabain was performed in adult dogs in order to describe the time course of the cardiovascular effect of intraventricular ouabain and to evaluate treatments to eliminate the cardiovascular effect. The central effect of ouabain caused a 56% increase in blood pressure above control values and a 35% increase in heart rate with various cardiac arrhythmias. Both alpha- and beta-adrenergic blocking drugs given intravenously.altered the pressure and rate effects ou ouabain, whereas vagotomy attenuated the effect."}
{"id": "PMID:4982", "title": "Effect of beta-adrenoreceptor blockade on rat cardiac and skeletal muscle pH.", "content": "The effect of catecholamines on the intracellular pH of rat cardiac and skeletal muscle during varying extracellular acid-base states was determined. Intracellualr pH (pHi) was calculated from the distribution of [14C]DMO. Acid-base disturbances were produced by placing the animals in an environmental chamber containing 10 or 20% CO2 or by administering HCL or NaHCO3. Two hours later the animals were anesthetized with sodium pentobarbital and blood and tissue samples obtained. In one series of animals, the effects of catecholamines were attenuated by administering the beta-adrenoreceptor antagonist MJ 1999 (Sotalol). In animals breathing 20% CO2, cardiac muscle pH was lower in beta-blocked than unblocked animals (6.69 vs. 6.78). During metabolic acidosis, cardiac muscle pH of beta-blocked animals was lower than that of unblocked animals (6.75 vs. 6.84). The same relationship was observed for skeletal muscle during metabolic acidosis-beta blockade pHi, 6.66; unblocked pHi, 6.77. The pHi of beta-blocked versus unblocked animals was not significantly different under normal acid-base conditions or metabolic alkalosis for cardiac or skeletal muscle. The effective buffer value of both tissue over the normal acidotic range was decreased by the beta-blocking agent. These results indicate that catecholamine release accompanying acidosis attenuates the change in pHI and increases the effective buffer value of cardiac and skeletal muscle.", "contents": "Effect of beta-adrenoreceptor blockade on rat cardiac and skeletal muscle pH. The effect of catecholamines on the intracellular pH of rat cardiac and skeletal muscle during varying extracellular acid-base states was determined. Intracellualr pH (pHi) was calculated from the distribution of [14C]DMO. Acid-base disturbances were produced by placing the animals in an environmental chamber containing 10 or 20% CO2 or by administering HCL or NaHCO3. Two hours later the animals were anesthetized with sodium pentobarbital and blood and tissue samples obtained. In one series of animals, the effects of catecholamines were attenuated by administering the beta-adrenoreceptor antagonist MJ 1999 (Sotalol). In animals breathing 20% CO2, cardiac muscle pH was lower in beta-blocked than unblocked animals (6.69 vs. 6.78). During metabolic acidosis, cardiac muscle pH of beta-blocked animals was lower than that of unblocked animals (6.75 vs. 6.84). The same relationship was observed for skeletal muscle during metabolic acidosis-beta blockade pHi, 6.66; unblocked pHi, 6.77. The pHi of beta-blocked versus unblocked animals was not significantly different under normal acid-base conditions or metabolic alkalosis for cardiac or skeletal muscle. The effective buffer value of both tissue over the normal acidotic range was decreased by the beta-blocking agent. These results indicate that catecholamine release accompanying acidosis attenuates the change in pHI and increases the effective buffer value of cardiac and skeletal muscle."}
{"id": "PMID:4983", "title": "Biliary secretion in elasmobranchs. I. Bile collection and composition.", "content": "Bile composition and secretion were studied in tow elasmobranch species, Squalus acanthias (spiny dogfish shark) and Raja erinacea (small skate), after ligation of the common duct and insertion of cannulas into the gallbladder lumen. Fish were then allowed to swim freely in large pools and bile was collected in balloons attached to the externalized cannulas. Both species secreted bile for periods of 4-7 days at a maximum rate of 1.77 +/- .89 ml/kg per 24 h in Squalus acanthias and 2.66 +/- .89 ml/kg per 24 h in Raja erinacea. Comparison of the composition of cannula and gallbladder bile indicated that hepatic bile could be collected by this technique in both species without effective contact with gallbladder epithelium. The low concentrations of HCO3- and CL- and the gigh bile salt levels in dogfish gallbladder bile indicate that mechanisms for concentration and acidification of bile in the gallbladder developed early in vertebrate evolution. These results indicate that gallbladder cannulation in free-swimming elasmobranchs is a useful technique for the study of bile secretory and excretory function in marine species.", "contents": "Biliary secretion in elasmobranchs. I. Bile collection and composition. Bile composition and secretion were studied in tow elasmobranch species, Squalus acanthias (spiny dogfish shark) and Raja erinacea (small skate), after ligation of the common duct and insertion of cannulas into the gallbladder lumen. Fish were then allowed to swim freely in large pools and bile was collected in balloons attached to the externalized cannulas. Both species secreted bile for periods of 4-7 days at a maximum rate of 1.77 +/- .89 ml/kg per 24 h in Squalus acanthias and 2.66 +/- .89 ml/kg per 24 h in Raja erinacea. Comparison of the composition of cannula and gallbladder bile indicated that hepatic bile could be collected by this technique in both species without effective contact with gallbladder epithelium. The low concentrations of HCO3- and CL- and the gigh bile salt levels in dogfish gallbladder bile indicate that mechanisms for concentration and acidification of bile in the gallbladder developed early in vertebrate evolution. These results indicate that gallbladder cannulation in free-swimming elasmobranchs is a useful technique for the study of bile secretory and excretory function in marine species."}
{"id": "PMID:4984", "title": "Film screening by physician assistants in diagnostic radiology.", "content": "Data are presented which indicate that specially selected ART students can be trained to evaluate radiographs as to the presence or absence of significant pathology with an accuracy equivalent to that of experienced staff radiologists. The methods employed in this training program-namely, stressing perceptual recognition of normal and abnormal findings-may be beneficial in the early months of training of diagnostic radiology residents to hasten achievement of an acceptable perceptual performance. Test films, used in this study as an evaluation technique, may also be useful to assess residents' progress.", "contents": "Film screening by physician assistants in diagnostic radiology. Data are presented which indicate that specially selected ART students can be trained to evaluate radiographs as to the presence or absence of significant pathology with an accuracy equivalent to that of experienced staff radiologists. The methods employed in this training program-namely, stressing perceptual recognition of normal and abnormal findings-may be beneficial in the early months of training of diagnostic radiology residents to hasten achievement of an acceptable perceptual performance. Test films, used in this study as an evaluation technique, may also be useful to assess residents' progress."}
{"id": "PMID:4985", "title": "Use of physician's assistants in a general surgical practice.", "content": "A study has been made of three PAS employed in a rural, small town, general surgical practice during a four year period. Their work was equally divided among three areas: minor trauma, obtaining and recording data for history and physical examinations, and assisting at routine surgical procedures and endoscopies. This resulted in a significant saving of time for each surgeon who was thus freed for more time in the care of the more critically ill or injured patients.", "contents": "Use of physician's assistants in a general surgical practice. A study has been made of three PAS employed in a rural, small town, general surgical practice during a four year period. Their work was equally divided among three areas: minor trauma, obtaining and recording data for history and physical examinations, and assisting at routine surgical procedures and endoscopies. This resulted in a significant saving of time for each surgeon who was thus freed for more time in the care of the more critically ill or injured patients."}
{"id": "PMID:4989", "title": "[The influence of PaCO2 on oxygen consumption during extracorporeal circulation in hypothermia (author's transl)].", "content": "Hypocapnia during extracorporeal circulation in hypothermia increases oxygen consumption. Po2 in mixed venous blood decreases. This probably reflects a decrease in tissue oxygen tension. Hyperventilation will therefore increase the risk of hypoxia in critically perfused tissues. Therefore we recommend to keep PaCO2 (T) constant at 40 mm Hg during hypothermia.", "contents": "[The influence of PaCO2 on oxygen consumption during extracorporeal circulation in hypothermia (author's transl)]. Hypocapnia during extracorporeal circulation in hypothermia increases oxygen consumption. Po2 in mixed venous blood decreases. This probably reflects a decrease in tissue oxygen tension. Hyperventilation will therefore increase the risk of hypoxia in critically perfused tissues. Therefore we recommend to keep PaCO2 (T) constant at 40 mm Hg during hypothermia."}
{"id": "PMID:4990", "title": "[Clinical studies on the use of ketalar in obstetric anesthesia (author's transl)].", "content": "26 healthy pregnant women at term were divided into 2 groups and anaesthetized with either 1 mg/kh or 2 mg/kg ketamine - N20/02 - for primary caesarean section. Maternal venous ketamine plasma levels, neonatal ketamine plasma levels (umbilical artery and umbilical vein) and blood gases were measured. Maternal venous ketamine plasma levels in group I exceeded those in group II by 2.8 (30-60 sec after injection) and 2.0 (at the time of delivery) respectively. Independent of the dose used, the plasma levels of ketamine in the umbilical artery or the umbilical vein were found to be identical in the two groups of newborn infants. Neonatal blood gases and acid base parameters did not significantly differ between the two groups, except for the oxygen tension in group II which slightly exceeded the PO2 values in group I 15, 60 and 120 min after delivery. pH and standard bicarbonate values were found to be higher (1 and 5 min) in both groups, compared to pH and standard bicarbonate levels in a group of newborns delivered spontaneously.--The results of this study show: 1. Independent of a low or high ketamine dosage, neonatal blood concentration of the drug remain low, probably due to a placental barrier effect.--2. The post partum recovery of the newborns was neither influenced by the ketamine anesthesia itself nor by different drug doses.", "contents": "[Clinical studies on the use of ketalar in obstetric anesthesia (author's transl)]. 26 healthy pregnant women at term were divided into 2 groups and anaesthetized with either 1 mg/kh or 2 mg/kg ketamine - N20/02 - for primary caesarean section. Maternal venous ketamine plasma levels, neonatal ketamine plasma levels (umbilical artery and umbilical vein) and blood gases were measured. Maternal venous ketamine plasma levels in group I exceeded those in group II by 2.8 (30-60 sec after injection) and 2.0 (at the time of delivery) respectively. Independent of the dose used, the plasma levels of ketamine in the umbilical artery or the umbilical vein were found to be identical in the two groups of newborn infants. Neonatal blood gases and acid base parameters did not significantly differ between the two groups, except for the oxygen tension in group II which slightly exceeded the PO2 values in group I 15, 60 and 120 min after delivery. pH and standard bicarbonate values were found to be higher (1 and 5 min) in both groups, compared to pH and standard bicarbonate levels in a group of newborns delivered spontaneously.--The results of this study show: 1. Independent of a low or high ketamine dosage, neonatal blood concentration of the drug remain low, probably due to a placental barrier effect.--2. The post partum recovery of the newborns was neither influenced by the ketamine anesthesia itself nor by different drug doses."}
{"id": "PMID:4998", "title": "Effect of abdominal compression on minute ventilation of patients with chronic obstructive lung disease and bronchial asthma.", "content": "The effects of manual compression of the upper lateral abdomen (C) of 73 cases of obstructive airway disease were studied in respect to the change in minute ventilation (V) 10 minutes after the procedure was performed. A mean decrease of 13% in V was found in the majority of 15 cases of bronchial asthma or chronic bronchitis and 43 patients with chronic obstructive lung disease. The use of manual compression as a therapeutic measure depends largely on the abrupt reduction of lung volume in cases of obstructive airway disease in which over-inflation of the lung is present as an acute or chronic disorder. The degree and duration of clinical benefit, i.e., relief of dyspnea, depends on such factors as the volume of air trapped in the lungs, broncho-constriction through pathologic change or bronchospasm and impairment of elastic recoil of the pulmonary parenchyma. The lowered V recorded 10 minutes after C is performed suggests that decrease in dyspnea is associated with enhanced efficiency of ventilation in some subjects with obstructive airway disease, including those with bronchial asthma as well as COLD. A brief description is presented of 10 patients with COLD in whom manual compression and other features of a rehabilitation program were employed. Mean length of life of five living subjects is 12.6 years after beginning of therapy. The mean length of life of five who died was 10.2 years after beginning of treatment.", "contents": "Effect of abdominal compression on minute ventilation of patients with chronic obstructive lung disease and bronchial asthma. The effects of manual compression of the upper lateral abdomen (C) of 73 cases of obstructive airway disease were studied in respect to the change in minute ventilation (V) 10 minutes after the procedure was performed. A mean decrease of 13% in V was found in the majority of 15 cases of bronchial asthma or chronic bronchitis and 43 patients with chronic obstructive lung disease. The use of manual compression as a therapeutic measure depends largely on the abrupt reduction of lung volume in cases of obstructive airway disease in which over-inflation of the lung is present as an acute or chronic disorder. The degree and duration of clinical benefit, i.e., relief of dyspnea, depends on such factors as the volume of air trapped in the lungs, broncho-constriction through pathologic change or bronchospasm and impairment of elastic recoil of the pulmonary parenchyma. The lowered V recorded 10 minutes after C is performed suggests that decrease in dyspnea is associated with enhanced efficiency of ventilation in some subjects with obstructive airway disease, including those with bronchial asthma as well as COLD. A brief description is presented of 10 patients with COLD in whom manual compression and other features of a rehabilitation program were employed. Mean length of life of five living subjects is 12.6 years after beginning of therapy. The mean length of life of five who died was 10.2 years after beginning of treatment."}
{"id": "PMID:5005", "title": "[Accidental peroperative hypothermia during rapid transfusion].", "content": "Six cases of grave hypothermias are reported, having arisen during surgical interventions which necessitated a rapid and abundant transfusion of badly warmed blood. The role of favouring factors, surrounding cold due to the air-conditioning, anaesthesia, extent of the area of operation, seems important. The symptomatology permits the individualization of a hypothermic syndrom neighbouring the picture described in toxic accidental hypothermias. Accidents during the warming process associate collapse and disturbances in coagulation. It is therefore necessary to consider certain signs of alarm as important and generalize the conditions for prevention of thermolysis in the operating theatre.", "contents": "[Accidental peroperative hypothermia during rapid transfusion]. Six cases of grave hypothermias are reported, having arisen during surgical interventions which necessitated a rapid and abundant transfusion of badly warmed blood. The role of favouring factors, surrounding cold due to the air-conditioning, anaesthesia, extent of the area of operation, seems important. The symptomatology permits the individualization of a hypothermic syndrom neighbouring the picture described in toxic accidental hypothermias. Accidents during the warming process associate collapse and disturbances in coagulation. It is therefore necessary to consider certain signs of alarm as important and generalize the conditions for prevention of thermolysis in the operating theatre."}
{"id": "PMID:5006", "title": "[Information science in intensive care medicine. Examples of the European approach].", "content": "The modern treatment of patients in a precarious state requires the use of technical appliances which become more complex and more numerous day by day. The data generated by these appliances, together with the conventional measurements of physiological parameters carried out by the nursing ataff during care, with the results of laboratory examinations and with medical physical examinations, represent a raw material of information which tends to increase each year. The repetitive and hand-written consigning of these data, likewise their traditional laborious consultation, no longer guarantees today the taking of rapid decisions concerning the patients. Now, this rapid decision-making is at the centre of the functioning of present-day intensive medicine, of the surveillance and optimal treatment of the patients, of the functional organization of the intensive care unit, and of the \"economic\" efficiency of the exploitation. It seems locigal, therefore, to wish to avail of the resources provided by information science to resolve these problems. The United States, Japan and certain European countries have done so. Our purpose is to give some examples of the European approach.", "contents": "[Information science in intensive care medicine. Examples of the European approach]. The modern treatment of patients in a precarious state requires the use of technical appliances which become more complex and more numerous day by day. The data generated by these appliances, together with the conventional measurements of physiological parameters carried out by the nursing ataff during care, with the results of laboratory examinations and with medical physical examinations, represent a raw material of information which tends to increase each year. The repetitive and hand-written consigning of these data, likewise their traditional laborious consultation, no longer guarantees today the taking of rapid decisions concerning the patients. Now, this rapid decision-making is at the centre of the functioning of present-day intensive medicine, of the surveillance and optimal treatment of the patients, of the functional organization of the intensive care unit, and of the \"economic\" efficiency of the exploitation. It seems locigal, therefore, to wish to avail of the resources provided by information science to resolve these problems. The United States, Japan and certain European countries have done so. Our purpose is to give some examples of the European approach."}
{"id": "PMID:5007", "title": "[Iskedyl and general anesthesia. Measurement of the systolic ejection volume and peripheral resistance using the arterial pressure curves].", "content": "ISKEDYL (PF 50), which is sold as a vasoregulator of cerebral irrigation, consists of a mixture of dihydroergocristine and raubasine. This work aims at determining possible interactions between this product and certain drugs used in anesthesia from the cardiovascular point of view. ISKEDYL does not seem to be a contraindication to anesthesia of the \"neuroleptic\" type, when injected in pre-, per- or post-operative period. A slight temporary and spontaneously reversible fall in arterial blood pressure, affecting both maximum and minimum pressure, together with a decrease in stroke volume and peripheral resistances, estimated by the study of the arterial blood pressure curve, seem to indicate that this product has peripheral vaso-dilatory properties.", "contents": "[Iskedyl and general anesthesia. Measurement of the systolic ejection volume and peripheral resistance using the arterial pressure curves]. ISKEDYL (PF 50), which is sold as a vasoregulator of cerebral irrigation, consists of a mixture of dihydroergocristine and raubasine. This work aims at determining possible interactions between this product and certain drugs used in anesthesia from the cardiovascular point of view. ISKEDYL does not seem to be a contraindication to anesthesia of the \"neuroleptic\" type, when injected in pre-, per- or post-operative period. A slight temporary and spontaneously reversible fall in arterial blood pressure, affecting both maximum and minimum pressure, together with a decrease in stroke volume and peripheral resistances, estimated by the study of the arterial blood pressure curve, seem to indicate that this product has peripheral vaso-dilatory properties."}
{"id": "PMID:5008", "title": "[Continuous peridural anesthesia in traumatological and reparative surgery of the lower extremities].", "content": "The authors give an account of their experience of peridural anaesthesia in 250 cases at the Centre for traumatological and reparative surgery. They demonstrate the advantages derived from this type of anaesthesia: in elderly subjects manifesting an organic defect, and in emergency cases with \"full stomach\".", "contents": "[Continuous peridural anesthesia in traumatological and reparative surgery of the lower extremities]. The authors give an account of their experience of peridural anaesthesia in 250 cases at the Centre for traumatological and reparative surgery. They demonstrate the advantages derived from this type of anaesthesia: in elderly subjects manifesting an organic defect, and in emergency cases with \"full stomach\"."}
{"id": "PMID:5004", "title": "[Disorders of body temperature regulation. 1. Physiopathological study].", "content": "In this work, disorders of thermo-regulation are first studied in a synthetic manner from the angle of cellular and haemodynamic disturbances. Then the particular physiopathological aspects concerning hypothermia and hyperthermia are looked at in succession. In his next work, the author will view the clinical and therapeutic study of these phenomena. Extensive bibliography.", "contents": "[Disorders of body temperature regulation. 1. Physiopathological study]. In this work, disorders of thermo-regulation are first studied in a synthetic manner from the angle of cellular and haemodynamic disturbances. Then the particular physiopathological aspects concerning hypothermia and hyperthermia are looked at in succession. In his next work, the author will view the clinical and therapeutic study of these phenomena. Extensive bibliography."}
{"id": "PMID:5014", "title": "[Physico-chemical characteristics, absorption and elimination kinetics and technics of use of enflurane].", "content": "Physical-chemical properties, uptake und elemination of enflurane are described with particular references to halothane. The ratio potency/vapor pressure, the blood and tissues solubility of this agent provide a good flexibility of uptake and elemination in response to changes in alveolar ventilation. When used with nitrous oxide, the enflurane may provide good clinical results at inspired concentration 1-2 p. 100.", "contents": "[Physico-chemical characteristics, absorption and elimination kinetics and technics of use of enflurane]. Physical-chemical properties, uptake und elemination of enflurane are described with particular references to halothane. The ratio potency/vapor pressure, the blood and tissues solubility of this agent provide a good flexibility of uptake and elemination in response to changes in alveolar ventilation. When used with nitrous oxide, the enflurane may provide good clinical results at inspired concentration 1-2 p. 100."}
{"id": "PMID:5009", "title": "[Impact of alfatesine anesthesia on cerebrospinal fluid pressure in man].", "content": "The variations in pressure of the cerebrospinal fluid was studied in 20 patients before and after induction of anesthesia with alfatesine (0.1 ml/Kg). 14 patients received no other complementary drug (group 1); in the six other cases, 1 g. of acetylsalicylic acid was administered as an analgesic complement (group II). All of the patients spontnaeously ventilated an O2 - N2O 50 p. 100 mixture. The C.S.F. pressure fell by 39 p. 100 on the average (p. less than 0.001) in group I and did not vary in group II. This fall is essentially related to cerebral vasoconstriction, therefore to the fall in cerebral blood flow caused by Alfatesine. In group II hypercapnia was noted in all of the patients; it abolishes the cerebral vasoconstriction due to Alfatesine; the cerebral blood flow did not fall neither did the C.S.F. pressure.", "contents": "[Impact of alfatesine anesthesia on cerebrospinal fluid pressure in man]. The variations in pressure of the cerebrospinal fluid was studied in 20 patients before and after induction of anesthesia with alfatesine (0.1 ml/Kg). 14 patients received no other complementary drug (group 1); in the six other cases, 1 g. of acetylsalicylic acid was administered as an analgesic complement (group II). All of the patients spontnaeously ventilated an O2 - N2O 50 p. 100 mixture. The C.S.F. pressure fell by 39 p. 100 on the average (p. less than 0.001) in group I and did not vary in group II. This fall is essentially related to cerebral vasoconstriction, therefore to the fall in cerebral blood flow caused by Alfatesine. In group II hypercapnia was noted in all of the patients; it abolishes the cerebral vasoconstriction due to Alfatesine; the cerebral blood flow did not fall neither did the C.S.F. pressure."}
{"id": "PMID:5010", "title": "[Transformation of sorbitol to mannitol when used in parenteral administration].", "content": "This was shown by the unexpected discovery of the urinary excretion of mannitol when urinary sorbitol levels were being measured in connection with the surveillance of patients suffering from malnutrition and head injury and receiving total parenteral nutrition: glucose, sorbitol, amino-acids, soya oil. The presence of mannitol in the urine would appear to result from a secondary catabolic through physiological pathway for the fructose produced by the metabolism of sortibol not metabolised during glycolysis.", "contents": "[Transformation of sorbitol to mannitol when used in parenteral administration]. This was shown by the unexpected discovery of the urinary excretion of mannitol when urinary sorbitol levels were being measured in connection with the surveillance of patients suffering from malnutrition and head injury and receiving total parenteral nutrition: glucose, sorbitol, amino-acids, soya oil. The presence of mannitol in the urine would appear to result from a secondary catabolic through physiological pathway for the fructose produced by the metabolism of sortibol not metabolised during glycolysis."}
{"id": "PMID:5015", "title": "[Clinical evaluation of the new anesthetic \"Ethrane\"].", "content": "Seventy-four patients aged 14 months to 71 years, classified as ASA I and II were anesthetised with Ethrane for surgical interventions of mean duration 117 minutes. With the exception of 5 patients who were directly anesthetised with Ethrane, the others received Ethrane after induction with Penthiobarbitone. Maintenance of anesthesia was ensured with 1 to 4p. 100 concentrations of Ethrane and 33p. 100 oxygen and 66p. 100 nitrous oxide. Tracheal intubation was facilitated by injection of 1 mg/kg of succinylcholine. Induction with enflurane is rapid with no phenomena of excitation or irritation of the ear passages. The cardiovascular apparatus is stable with no arrythmia but an increase in heart rate of 11 to 50p. 100 is noted and in 41p. 100 of the cases hypotension of 35p. 100 of the intitial value. During spontaneous ventilation, a type of rapid and superficial respiration is observed with a flow volume of 5.3 ml/kg for an average frequency of 25/min. The arterial blood gases show slight hypercapnia. Myorelaxation is significant and better than that obtained with halothane. Coming round poses few problems apart from agitation in adolescents. Response to simple orders appears at 13 minutes. Trembling and rigidity occur in 41p. 100 of the cases for 5 to 30 minutes. From the hepatic point of view, no lastin enzyme changes were noted and no renal toxicity was demonstrated. Ethrane appears to be a good anesthetic agent but the few advantages mentioned means that it does not fulfil ideal conditions.", "contents": "[Clinical evaluation of the new anesthetic \"Ethrane\"]. Seventy-four patients aged 14 months to 71 years, classified as ASA I and II were anesthetised with Ethrane for surgical interventions of mean duration 117 minutes. With the exception of 5 patients who were directly anesthetised with Ethrane, the others received Ethrane after induction with Penthiobarbitone. Maintenance of anesthesia was ensured with 1 to 4p. 100 concentrations of Ethrane and 33p. 100 oxygen and 66p. 100 nitrous oxide. Tracheal intubation was facilitated by injection of 1 mg/kg of succinylcholine. Induction with enflurane is rapid with no phenomena of excitation or irritation of the ear passages. The cardiovascular apparatus is stable with no arrythmia but an increase in heart rate of 11 to 50p. 100 is noted and in 41p. 100 of the cases hypotension of 35p. 100 of the intitial value. During spontaneous ventilation, a type of rapid and superficial respiration is observed with a flow volume of 5.3 ml/kg for an average frequency of 25/min. The arterial blood gases show slight hypercapnia. Myorelaxation is significant and better than that obtained with halothane. Coming round poses few problems apart from agitation in adolescents. Response to simple orders appears at 13 minutes. Trembling and rigidity occur in 41p. 100 of the cases for 5 to 30 minutes. From the hepatic point of view, no lastin enzyme changes were noted and no renal toxicity was demonstrated. Ethrane appears to be a good anesthetic agent but the few advantages mentioned means that it does not fulfil ideal conditions."}
{"id": "PMID:5011", "title": "[A case of acute tobacco poisoning by enema].", "content": "The authors report the case of a 5 month old child intoxicated with nicotine through an enema. A mother who wished to treat her infant for constipation had administered to him as an enema a decoction of green tobacco leaves; 15 to 20 minutes after the enema, the child showed diarrhoea and respiratory disturbances. The authors treated the respiratory disturbances by assisted respiration and bradycardia and the diarrhoea with atropine. They also caused a force diuresis using a 10 p. 100 glucose solution and Furosemide.", "contents": "[A case of acute tobacco poisoning by enema]. The authors report the case of a 5 month old child intoxicated with nicotine through an enema. A mother who wished to treat her infant for constipation had administered to him as an enema a decoction of green tobacco leaves; 15 to 20 minutes after the enema, the child showed diarrhoea and respiratory disturbances. The authors treated the respiratory disturbances by assisted respiration and bradycardia and the diarrhoea with atropine. They also caused a force diuresis using a 10 p. 100 glucose solution and Furosemide."}
{"id": "PMID:5016", "title": "[Hemodynamic effect of enflurane in man].", "content": "The following hemodynamic parameters: cardiac frequency, peripheral arterial pressure, pulmonary pressure and cardiac output were measured by direct catheterisation, as the total peripheral vascular resistance and the systolic ejection volume were calculated from the registered results. The cardiac frequency and the pulmonary arterial pressure were practically not modified in our patients, though we have observed a statistically significant decrease of systolic (-30p. 100) and diastolic (-27p. 100) arterial pressure. The total peripheral vascular resistance shows a marked diminution (-20p. 100) after giving Ethrane? for ten minutes. If it is possible that one part, surely important, of the cardiac output, is preserved under Ethrane anesthesia by a significant decrease of the total peripheral vascular resistance, a myocardial depression might be questionned, the decrease of cardiac output at 30 minutes being more important than the decrease of the total peripheral vascular resistance.", "contents": "[Hemodynamic effect of enflurane in man]. The following hemodynamic parameters: cardiac frequency, peripheral arterial pressure, pulmonary pressure and cardiac output were measured by direct catheterisation, as the total peripheral vascular resistance and the systolic ejection volume were calculated from the registered results. The cardiac frequency and the pulmonary arterial pressure were practically not modified in our patients, though we have observed a statistically significant decrease of systolic (-30p. 100) and diastolic (-27p. 100) arterial pressure. The total peripheral vascular resistance shows a marked diminution (-20p. 100) after giving Ethrane? for ten minutes. If it is possible that one part, surely important, of the cardiac output, is preserved under Ethrane anesthesia by a significant decrease of the total peripheral vascular resistance, a myocardial depression might be questionned, the decrease of cardiac output at 30 minutes being more important than the decrease of the total peripheral vascular resistance."}
{"id": "PMID:5017", "title": "[Postoperative circulatory arrest (apropos of 37 cases)].", "content": "Within five years, the authors received 37 patients who had presented a post-operative cardiac arrest. Most of them came from the Bordeaux district (from the hospital as well as the public sector) although they did not represent the totality of such accidents. The study bears first of all upon the data concerning the patients, then upon the surgical intervention, the mode of anaesthesia and ventilation, the posture and finally the treatment. In 10 cases. it was noted, as early as the admission, that the blood volume feel short of the theoretical total blood volume by one liter or more. The authors take into account how traces of previous affections, the localization in O.R.L., and, in ophthalmology, an important number of mistakes in anaesthesia, favour the progress of the genesis of the accident.", "contents": "[Postoperative circulatory arrest (apropos of 37 cases)]. Within five years, the authors received 37 patients who had presented a post-operative cardiac arrest. Most of them came from the Bordeaux district (from the hospital as well as the public sector) although they did not represent the totality of such accidents. The study bears first of all upon the data concerning the patients, then upon the surgical intervention, the mode of anaesthesia and ventilation, the posture and finally the treatment. In 10 cases. it was noted, as early as the admission, that the blood volume feel short of the theoretical total blood volume by one liter or more. The authors take into account how traces of previous affections, the localization in O.R.L., and, in ophthalmology, an important number of mistakes in anaesthesia, favour the progress of the genesis of the accident."}
{"id": "PMID:5018", "title": "[New ventilation technic in anesthesia for direct suspension laryngoscopy].", "content": "The authors bring not only the results of their experience but a solution of the respiratory problems during anaesthesia in suspension laryngoscopy, thanks to the devising of a new intubation probe and a pre-set automatic insufflator with varying volum flow.", "contents": "[New ventilation technic in anesthesia for direct suspension laryngoscopy]. The authors bring not only the results of their experience but a solution of the respiratory problems during anaesthesia in suspension laryngoscopy, thanks to the devising of a new intubation probe and a pre-set automatic insufflator with varying volum flow."}
{"id": "PMID:5019", "title": "[The second electromyographic study of surgical curarization with AH.8165, a new pachycurare derivative of azobis-arylimidazo(1-2a) pyridinium].", "content": "This second electromyographic study of AH-8165, a product derived from azobis-arymilidazo-(1-2a) pyridinium, carried out with a special apparatus which both stimulates and records, specifies the characteristics of the neuro-muscular block induced by this new non-depolarizing type curarizing substance while taking into account the usual factors of the curarimimetic variability of action. After an initial dose of 1 mg per kg of bodyweight, we notice particularly: -the lapse of time required for a complete block (90 s), its intensity and duration (normally total during at least one hour) -the morphology of the electromyogram during the curarization and the decurarization either spontaneous or induced by Neostigmin with in particular -the muscular fatigability after repeated stimulation following curarization and chiefly during decurarization, chronological data und electro-myographic aspects which are found as well after a reinjection of AH-8165 equivalent to the half of the previous one.", "contents": "[The second electromyographic study of surgical curarization with AH.8165, a new pachycurare derivative of azobis-arylimidazo(1-2a) pyridinium]. This second electromyographic study of AH-8165, a product derived from azobis-arymilidazo-(1-2a) pyridinium, carried out with a special apparatus which both stimulates and records, specifies the characteristics of the neuro-muscular block induced by this new non-depolarizing type curarizing substance while taking into account the usual factors of the curarimimetic variability of action. After an initial dose of 1 mg per kg of bodyweight, we notice particularly: -the lapse of time required for a complete block (90 s), its intensity and duration (normally total during at least one hour) -the morphology of the electromyogram during the curarization and the decurarization either spontaneous or induced by Neostigmin with in particular -the muscular fatigability after repeated stimulation following curarization and chiefly during decurarization, chronological data und electro-myographic aspects which are found as well after a reinjection of AH-8165 equivalent to the half of the previous one."}
{"id": "PMID:5020", "title": "[Contribution to the study of Trive 1000].", "content": "A glucid-lipid and protein compound nutriment: Trive 1000 was administered to 53 patients during the first three postoperative days in varying doses: -1.000 ml per day to a first group -1.500 ml per day to a second group. The local tolerance was quite good. However, a few accidents of a general character were noted: they were due to a great extent to a non-observance of the rules of preservation. A study of the glucides, in Sorbitol form, showed a good assimilation of the substratum. Glycemia remaining within normal, no glycosuria or ketonuria could be observed. The assimilation of the proteins seemed on the whole satisfactory. No important rise in the blood urea was noted. Nitrogen balances showed that, thanks to this nutriment, almost half of them were positive during the post-aggressive period. The more important the dose of Trive 1000, the more positive the nitrogen balances were. The administration of lipids did not reveal any significant change in the total lipids, triglycerides or cholesterol. A study of the graphic record of lipid levels showed chylomicrons twice. On the opposite, lipoproteins were hardly modified apart from a significant in pre-beta lipoproteins. The quantitative analysis of amino-acids proved interesting. A comparative study of amino-acids both in blood and urine before and after the administration of Trive 1000 showed very little variations in connection with essential amino-acids. If the proportions in the blood of non-essential amino-acids were comparatively but little modified before and after the treatment, on the oppostie, the urinary clearance rate of the same amino-acids after treatment was far more variable and often quite important as far as certain amino-acids were concerned.", "contents": "[Contribution to the study of Trive 1000]. A glucid-lipid and protein compound nutriment: Trive 1000 was administered to 53 patients during the first three postoperative days in varying doses: -1.000 ml per day to a first group -1.500 ml per day to a second group. The local tolerance was quite good. However, a few accidents of a general character were noted: they were due to a great extent to a non-observance of the rules of preservation. A study of the glucides, in Sorbitol form, showed a good assimilation of the substratum. Glycemia remaining within normal, no glycosuria or ketonuria could be observed. The assimilation of the proteins seemed on the whole satisfactory. No important rise in the blood urea was noted. Nitrogen balances showed that, thanks to this nutriment, almost half of them were positive during the post-aggressive period. The more important the dose of Trive 1000, the more positive the nitrogen balances were. The administration of lipids did not reveal any significant change in the total lipids, triglycerides or cholesterol. A study of the graphic record of lipid levels showed chylomicrons twice. On the opposite, lipoproteins were hardly modified apart from a significant in pre-beta lipoproteins. The quantitative analysis of amino-acids proved interesting. A comparative study of amino-acids both in blood and urine before and after the administration of Trive 1000 showed very little variations in connection with essential amino-acids. If the proportions in the blood of non-essential amino-acids were comparatively but little modified before and after the treatment, on the oppostie, the urinary clearance rate of the same amino-acids after treatment was far more variable and often quite important as far as certain amino-acids were concerned."}
{"id": "PMID:5021", "title": "[Comparative study of nitrogen savings during enteral and parenteral feeding (Trive 1000)].", "content": "Through a study of Nitrogen balances, the authors compare the effectiveness of a proteinic intake carried out per os or by intravenous route. The study involved 22 different carcinoma carriers and lasted for 9 days during which the Nitrogen intake was effected either by the digestive tract or by intravenous route supplemented by a sufficient caloric ration. In the latter case, the aminoacid intake was supplied by Trive 1000 combined with glucides and lipids which were then quantitatively deducted from the enteral intake. A study of the results showed that the assimilation of the Nitrogen injected intravenously was very similar to the one obtained by enteral route.", "contents": "[Comparative study of nitrogen savings during enteral and parenteral feeding (Trive 1000)]. Through a study of Nitrogen balances, the authors compare the effectiveness of a proteinic intake carried out per os or by intravenous route. The study involved 22 different carcinoma carriers and lasted for 9 days during which the Nitrogen intake was effected either by the digestive tract or by intravenous route supplemented by a sufficient caloric ration. In the latter case, the aminoacid intake was supplied by Trive 1000 combined with glucides and lipids which were then quantitatively deducted from the enteral intake. A study of the results showed that the assimilation of the Nitrogen injected intravenously was very similar to the one obtained by enteral route."}
{"id": "PMID:5022", "title": "[The utilization of EB 51 in parenteral feeding. Clinical, biological and anatomopathological control. Statistical study on 30 patients].", "content": "Two groups of patients (comas of central origin and serious digestive undernourished) were submitted to an exclusive or a supplementary parenteral feeding for a short or a long period of time totaling over 500 days. The catheter was placed (in 80 p. cent of the cases) in a deep vein and was tunnellized. EB 51 (Trivemil) used in those 30 patients gives amino-acids, lipids and glucides. The caloric intake was completed by 30 p. cent glucose solutes. If the average caloric intake was 3.000 calories per day, it was often above that figure since the feeding was combined with a nutri-pump enteral feeding for 60 p. cent of the days. The clinical tolerance was quite good. On a biological level, in addition to classic investigations, 40 analytic graphic records of lipid levels were made, as well as a quantitative analysis of serous triglycerides and lipurias, a study of sorbitol and 500 nitrogen balances combined with 150 chromatographies on the acidaminuria column. An hepatic biological control was also made (amnoniemia, transaminases) as well as a quantitative analysis of lactates, pyruvates and minerals: iron-phosphorus-magnesium. Some of the results were checked by statistical studies. No serious anomaly was detected. Lung and hepatic biopsies carried out upon 9 patients did not apparently reveal any lipidic overloading. The clinical and the biological investigation show that this complete nutriment is perfectly tolerated and assimilated.", "contents": "[The utilization of EB 51 in parenteral feeding. Clinical, biological and anatomopathological control. Statistical study on 30 patients]. Two groups of patients (comas of central origin and serious digestive undernourished) were submitted to an exclusive or a supplementary parenteral feeding for a short or a long period of time totaling over 500 days. The catheter was placed (in 80 p. cent of the cases) in a deep vein and was tunnellized. EB 51 (Trivemil) used in those 30 patients gives amino-acids, lipids and glucides. The caloric intake was completed by 30 p. cent glucose solutes. If the average caloric intake was 3.000 calories per day, it was often above that figure since the feeding was combined with a nutri-pump enteral feeding for 60 p. cent of the days. The clinical tolerance was quite good. On a biological level, in addition to classic investigations, 40 analytic graphic records of lipid levels were made, as well as a quantitative analysis of serous triglycerides and lipurias, a study of sorbitol and 500 nitrogen balances combined with 150 chromatographies on the acidaminuria column. An hepatic biological control was also made (amnoniemia, transaminases) as well as a quantitative analysis of lactates, pyruvates and minerals: iron-phosphorus-magnesium. Some of the results were checked by statistical studies. No serious anomaly was detected. Lung and hepatic biopsies carried out upon 9 patients did not apparently reveal any lipidic overloading. The clinical and the biological investigation show that this complete nutriment is perfectly tolerated and assimilated."}
{"id": "PMID:5026", "title": "[Effect of increasing doses of dopamine on the left ventricular function in the dog].", "content": "A study on eleven dogs of the effects of increasing doses of dopamine on the left ventricular function. A description of the method which consists of a venous shunt connected to an extra-corporeal circuit and which allows modification simply and rapidly of the state of vascular refilling of the animal. The results differ according to the pressure-level of the refilling of the left ventricule. At low pressure, the dopamine increases the arterial pressure, the cardiac output and the systolic activity of the left ventricle for a reduced tachycardic effect. At higher pressure, the average aortic pressure is only slightly increased and the systolic activity is elevated without increase in cardiac output. These facts indicate dopamine in states of shock with a low pressure of refilling.", "contents": "[Effect of increasing doses of dopamine on the left ventricular function in the dog]. A study on eleven dogs of the effects of increasing doses of dopamine on the left ventricular function. A description of the method which consists of a venous shunt connected to an extra-corporeal circuit and which allows modification simply and rapidly of the state of vascular refilling of the animal. The results differ according to the pressure-level of the refilling of the left ventricule. At low pressure, the dopamine increases the arterial pressure, the cardiac output and the systolic activity of the left ventricle for a reduced tachycardic effect. At higher pressure, the average aortic pressure is only slightly increased and the systolic activity is elevated without increase in cardiac output. These facts indicate dopamine in states of shock with a low pressure of refilling."}
{"id": "PMID:5027", "title": "[The effect of intravenous dopamine on the hemodynamics of the heart].", "content": "The pharmacological study of dopamine was conducted on 14 patients: eleven normal patients and three with incipient myocardiopathies. The dosages used were 3, 6 and 12 mug/kg/min. The \"pump\" function, the peripheral resistances, the contractility and the ventricular compliance were studied. Dopamine is a positive inotropic agent without chronotropic action at doses of 6 and 12 mug/kg/min. It acts by increasing the contractility and the venous return and by decreasing the peripheral resistances; this effect disappears with strong dosages.", "contents": "[The effect of intravenous dopamine on the hemodynamics of the heart]. The pharmacological study of dopamine was conducted on 14 patients: eleven normal patients and three with incipient myocardiopathies. The dosages used were 3, 6 and 12 mug/kg/min. The \"pump\" function, the peripheral resistances, the contractility and the ventricular compliance were studied. Dopamine is a positive inotropic agent without chronotropic action at doses of 6 and 12 mug/kg/min. It acts by increasing the contractility and the venous return and by decreasing the peripheral resistances; this effect disappears with strong dosages."}
{"id": "PMID:5028", "title": "[Hemodynamic study of dopamine used in chronic heart failures and in cardiogenic shock as a complication of acute myocardial infarct].", "content": "The object of this study is to examine the properties of dopamine at the hemodynamic and renal level in 16 patients with decompensated chronic cardiopathies or very serious cardiogenic shock due to myocardial infarction. The results show an increase in the cardiac index in 75 p. 100 of the cases with a favourable diminution of the arterio-venous difference in O2 and of the pulmonary arterial resistances. The most noticeable and the most constant effect is the recovery and increase of the diuresis. Positive chronotropic and bathmotropic effects were observed which necessitated the limitation of prescription of dopamine in those subjects showing signs of disturbances in ventricular excitability.", "contents": "[Hemodynamic study of dopamine used in chronic heart failures and in cardiogenic shock as a complication of acute myocardial infarct]. The object of this study is to examine the properties of dopamine at the hemodynamic and renal level in 16 patients with decompensated chronic cardiopathies or very serious cardiogenic shock due to myocardial infarction. The results show an increase in the cardiac index in 75 p. 100 of the cases with a favourable diminution of the arterio-venous difference in O2 and of the pulmonary arterial resistances. The most noticeable and the most constant effect is the recovery and increase of the diuresis. Positive chronotropic and bathmotropic effects were observed which necessitated the limitation of prescription of dopamine in those subjects showing signs of disturbances in ventricular excitability."}
{"id": "PMID:5029", "title": "[Studies of the variations in functional renal values induced by intravenous dopamine].", "content": "We studied, on six patients, the variations in functional renal value and urinary excretion of electrolytes during the intravenous administration of dopamine and in the hours immediately following. Two groups of patients are distinguished. In groupe I, all of whom had normal functional renal values, there was no modification of these, while we observed increases in output, in excretion of electrolytes and in the clearance of the uric acid. In group II, composed of patients with renal insufficiencies, the modifications are less definite but the diuretic and saluretic effect is present. The salidiuretic effects of the dopamine would seem to be dissociated from the cardiovascular effects.", "contents": "[Studies of the variations in functional renal values induced by intravenous dopamine]. We studied, on six patients, the variations in functional renal value and urinary excretion of electrolytes during the intravenous administration of dopamine and in the hours immediately following. Two groups of patients are distinguished. In groupe I, all of whom had normal functional renal values, there was no modification of these, while we observed increases in output, in excretion of electrolytes and in the clearance of the uric acid. In group II, composed of patients with renal insufficiencies, the modifications are less definite but the diuretic and saluretic effect is present. The salidiuretic effects of the dopamine would seem to be dissociated from the cardiovascular effects."}
{"id": "PMID:5030", "title": "[The use of dopamine during postoperative cardiogenic shock in children. Preliminary results].", "content": "Dopamine was used in a dose of 5 mug/kg/min in ten infants with congenital cardiopathy and presenting in the immediate postoperative period a syndrome of low cardiac output. The output was not measured but, based on the evolution of the clinical signs, six favourable results, with correction of the syndrome, can be reported.", "contents": "[The use of dopamine during postoperative cardiogenic shock in children. Preliminary results]. Dopamine was used in a dose of 5 mug/kg/min in ten infants with congenital cardiopathy and presenting in the immediate postoperative period a syndrome of low cardiac output. The output was not measured but, based on the evolution of the clinical signs, six favourable results, with correction of the syndrome, can be reported."}
{"id": "PMID:5031", "title": "[Use of dopamine in postoperative reanimation after heart surgery. Preliminary results].", "content": "The dopamine was used on ten patients having undergone one or several valvular replacements under extra-corporeal circulation. The essential indication was the appearance postoperatively of more or less serious circulatory failure. The dopamine was administered by drip in doses of 2.5, 5 or 10 mug/kg/min. The effects on the frequency of the cardiac rhythm were moderate. On two cases, ventricular hyperexcitability induced by isoprenaline disappeared under dopamine. The chief effects were an increase in cardiac output, in the form of an increase in the volume of systolic ejection and lowering of the peripheral resistances. A steady increase in urinary volume preceded the amelioration of clinical signs of circulatory failure.", "contents": "[Use of dopamine in postoperative reanimation after heart surgery. Preliminary results]. The dopamine was used on ten patients having undergone one or several valvular replacements under extra-corporeal circulation. The essential indication was the appearance postoperatively of more or less serious circulatory failure. The dopamine was administered by drip in doses of 2.5, 5 or 10 mug/kg/min. The effects on the frequency of the cardiac rhythm were moderate. On two cases, ventricular hyperexcitability induced by isoprenaline disappeared under dopamine. The chief effects were an increase in cardiac output, in the form of an increase in the volume of systolic ejection and lowering of the peripheral resistances. A steady increase in urinary volume preceded the amelioration of clinical signs of circulatory failure."}
{"id": "PMID:5032", "title": "[Use of dopamine in acute cardiovascular distress. Its place in comparison to isoproterenol].", "content": "Nineteen patients presenting cardiovascular distress were treated with dopamine. For seventeen of these, the accident occurred immediately after cardiac surgery. Dosages varied from 1 to 15 mug/kg/min and the duration of treatment from 10 minutes to three days. The efficacy of the treatment was judged according to the clinical and hemodynamic improvement of the cardio-circulatory function and the increase in urinary output. There were 15 favourable results. The positive effects of the dopamine seem to be limited in certain patients by the appearance of a cyanosis testifying to a rise in vascular resistances which increases the left auricular pressure and limits the inotropic effect. In these cases, isoproterenol or a combination of both isoproterenol and dopamine gives better results.", "contents": "[Use of dopamine in acute cardiovascular distress. Its place in comparison to isoproterenol]. Nineteen patients presenting cardiovascular distress were treated with dopamine. For seventeen of these, the accident occurred immediately after cardiac surgery. Dosages varied from 1 to 15 mug/kg/min and the duration of treatment from 10 minutes to three days. The efficacy of the treatment was judged according to the clinical and hemodynamic improvement of the cardio-circulatory function and the increase in urinary output. There were 15 favourable results. The positive effects of the dopamine seem to be limited in certain patients by the appearance of a cyanosis testifying to a rise in vascular resistances which increases the left auricular pressure and limits the inotropic effect. In these cases, isoproterenol or a combination of both isoproterenol and dopamine gives better results."}
{"id": "PMID:5033", "title": "[Dopamine and shock. Preliminary clinical study of 7 cases].", "content": "Seven patients presenting a state of shock were treated with dopamine. The authors remark an undeniable effect on arterial pressure which rises again and on the diuresis.", "contents": "[Dopamine and shock. Preliminary clinical study of 7 cases]. Seven patients presenting a state of shock were treated with dopamine. The authors remark an undeniable effect on arterial pressure which rises again and on the diuresis."}
{"id": "PMID:5034", "title": "[Use of dopamine in the treatment of cardiogenic shock. Preliminary results].", "content": "A study of seven patients, each of whom was treated with dopamine within three hours after suffering a myocardial infarction. For four of these, a comparative study was made with isoproterenol, glucagon and ouabaine. The average age of the subjects was 72 years, and all presented considerable myocardial lesions before the treatment was begun. Despite improvement, particularly in diuresis and cardiac output, none of the patients survived. The authors explain these results by the fact that, like all powerful inotropic agents, dopamine produces an increase in oxygen consumption of the myocardium for the ischemic cells situated in the zone contiguous to the infarct.", "contents": "[Use of dopamine in the treatment of cardiogenic shock. Preliminary results]. A study of seven patients, each of whom was treated with dopamine within three hours after suffering a myocardial infarction. For four of these, a comparative study was made with isoproterenol, glucagon and ouabaine. The average age of the subjects was 72 years, and all presented considerable myocardial lesions before the treatment was begun. Despite improvement, particularly in diuresis and cardiac output, none of the patients survived. The authors explain these results by the fact that, like all powerful inotropic agents, dopamine produces an increase in oxygen consumption of the myocardium for the ischemic cells situated in the zone contiguous to the infarct."}
{"id": "PMID:5035", "title": "[Comparison of the endocrine response under 2 kinds of anesthesia: neuroleptanalgesia of the chlorprothixene-dextromoramide type and venous anesthesia of the type alfadione-fentanyl].", "content": "In 14 patients anaesthetized before undergoing an orthopedic surgical intervention, the variations induced by anaesthesia in the 17 hydroxycorticosterone rate, catecholamine, somatotropic hormone (STH), insulin, glycemia, free fatty acids and thyrotropin (TSH), all these variations were studied before the surgery. The patients were divided into 2 groups of 7, the first one being anaesthestized by chlorprothixene dextromoramide Neurolept-Analgesia and the second one by Alfadione Fentanyl venous anaesthesia.", "contents": "[Comparison of the endocrine response under 2 kinds of anesthesia: neuroleptanalgesia of the chlorprothixene-dextromoramide type and venous anesthesia of the type alfadione-fentanyl]. In 14 patients anaesthetized before undergoing an orthopedic surgical intervention, the variations induced by anaesthesia in the 17 hydroxycorticosterone rate, catecholamine, somatotropic hormone (STH), insulin, glycemia, free fatty acids and thyrotropin (TSH), all these variations were studied before the surgery. The patients were divided into 2 groups of 7, the first one being anaesthestized by chlorprothixene dextromoramide Neurolept-Analgesia and the second one by Alfadione Fentanyl venous anaesthesia."}
{"id": "PMID:5036", "title": "[The place of enflurane in neuro-anesthesia].", "content": "In neuro-anaesthesia, anaesthetic agents must be in accordance with certain criteria necessary to the preservation of the integrity of the brain. Therefore it was in such a perspective that we re-appraised the effects of enflurane upon cortical irritability, metabolism, cerebral blood flow and intracranial pressure. We reached the following conclusions: in normocapnia, and with optimal clinical concentrations, this drug remains the best anaesthetic agent since it has no harmful effect either upon metabolism or upon cerebral blood flow. However, in hypertensive cerebral lesions, caution is called for an it seems advisable to combine Enflurane with mild doses of fentanyl. Finally, anaesthesia with enflurane is followed by a rapid and smooth return to consciousness, a valuable factor in neurosurgery where post-operative neurological watching matters very much.", "contents": "[The place of enflurane in neuro-anesthesia]. In neuro-anaesthesia, anaesthetic agents must be in accordance with certain criteria necessary to the preservation of the integrity of the brain. Therefore it was in such a perspective that we re-appraised the effects of enflurane upon cortical irritability, metabolism, cerebral blood flow and intracranial pressure. We reached the following conclusions: in normocapnia, and with optimal clinical concentrations, this drug remains the best anaesthetic agent since it has no harmful effect either upon metabolism or upon cerebral blood flow. However, in hypertensive cerebral lesions, caution is called for an it seems advisable to combine Enflurane with mild doses of fentanyl. Finally, anaesthesia with enflurane is followed by a rapid and smooth return to consciousness, a valuable factor in neurosurgery where post-operative neurological watching matters very much."}
{"id": "PMID:5039", "title": "Immunology and microbiology in acute otitis media.", "content": "Various immunological parameters were measured in serum, middle ear fluid (MEF), and lymphocytes from peripheral blood and MEF of infants with acute otitis media due to S. pneumoniae or H. influenzae. Approximately half of 131 patients had IgE specific antibody to the infecting bacterium as determined by the indirect fluorescent antibody (IFA) technique. Seventy-one percent of these IgE positive patients had IgE specific antibody in the MEF. Total IgE concentration was found to be from an average of 1.5 to 3.0 times higher in the MEF when compared to the simultaneously drawn serum. In addition, antibody to pneumococcal capsular polysaccharides and to pneumococcal C-carbohydrate was demonstrated in the MEF by radioimmunoassay. When MEF specific antibody was compared to serum antibody it appeared that antibody to C-carbohydrate was more concentrated in the MEF. That this antibody was of the IgE class was suggested by IFA but not conclusively proven. Evidence exists that conditions for enhanced IgE synthesis is concomitantly associated with a decrease in T-cell activity. T-cell function in MEF derived lymphocytes as determined by rosette formation and by phytohemagglutinin (PHA) stimulation was approximately one-tenth that of the peripheral blood lymphocytes. However, that T-cells may participate in the immune response to polysaccharides was suggested by the observation that polysaccharide stimulated peripheral blood lymphocytes from infants immunized with octavalent pneumococcal capsular vaccine underwent protein synthesis two to three times that of the PHA stimulated cells. The clinical significance of this finding as well as the nature of the cell responsible for the increased protein synthesis remains to be established. It is hypothesized that acute otitis media results from local synthesis of bacteria specific IgE antibody which is enhanced by a paucity of local T-cell activity.", "contents": "Immunology and microbiology in acute otitis media. Various immunological parameters were measured in serum, middle ear fluid (MEF), and lymphocytes from peripheral blood and MEF of infants with acute otitis media due to S. pneumoniae or H. influenzae. Approximately half of 131 patients had IgE specific antibody to the infecting bacterium as determined by the indirect fluorescent antibody (IFA) technique. Seventy-one percent of these IgE positive patients had IgE specific antibody in the MEF. Total IgE concentration was found to be from an average of 1.5 to 3.0 times higher in the MEF when compared to the simultaneously drawn serum. In addition, antibody to pneumococcal capsular polysaccharides and to pneumococcal C-carbohydrate was demonstrated in the MEF by radioimmunoassay. When MEF specific antibody was compared to serum antibody it appeared that antibody to C-carbohydrate was more concentrated in the MEF. That this antibody was of the IgE class was suggested by IFA but not conclusively proven. Evidence exists that conditions for enhanced IgE synthesis is concomitantly associated with a decrease in T-cell activity. T-cell function in MEF derived lymphocytes as determined by rosette formation and by phytohemagglutinin (PHA) stimulation was approximately one-tenth that of the peripheral blood lymphocytes. However, that T-cells may participate in the immune response to polysaccharides was suggested by the observation that polysaccharide stimulated peripheral blood lymphocytes from infants immunized with octavalent pneumococcal capsular vaccine underwent protein synthesis two to three times that of the PHA stimulated cells. The clinical significance of this finding as well as the nature of the cell responsible for the increased protein synthesis remains to be established. It is hypothesized that acute otitis media results from local synthesis of bacteria specific IgE antibody which is enhanced by a paucity of local T-cell activity."}
{"id": "PMID:5040", "title": "Otitis media in the newborn infant.", "content": "Otitis media occurs frequently in newborn infants and often is associated with systemic infection. Patients studied at the Boston City Hospital have provided preliminary data on the otoscopic findings, tympanometric patterns and etiologic agents characteristic of otitis in this age group.", "contents": "Otitis media in the newborn infant. Otitis media occurs frequently in newborn infants and often is associated with systemic infection. Patients studied at the Boston City Hospital have provided preliminary data on the otoscopic findings, tympanometric patterns and etiologic agents characteristic of otitis in this age group."}
{"id": "PMID:5041", "title": "Microorganisms in chronic otitis media with effusion.", "content": "A total of 175 effusions obtained from 172 patients suffering from chronic otitis media with effusions was examined for bacterial smear and culture. Eighty percent showed positive bacterial smear, but only 49% yielded positive bacterial culture. The mucoid effusions had positive cultures in only 37%, whereas the bacterial culture rate was higher in serous (59%) and leukocytic (64%) types. The isolation of common pathogens accounted for about 50% of the isolates, and nonpathogens accounted for the remaining 50%. The high incidence of microorganisms in the middle ear effusions in the present series raises the possibility of bacterial contribution in many cases of OME.", "contents": "Microorganisms in chronic otitis media with effusion. A total of 175 effusions obtained from 172 patients suffering from chronic otitis media with effusions was examined for bacterial smear and culture. Eighty percent showed positive bacterial smear, but only 49% yielded positive bacterial culture. The mucoid effusions had positive cultures in only 37%, whereas the bacterial culture rate was higher in serous (59%) and leukocytic (64%) types. The isolation of common pathogens accounted for about 50% of the isolates, and nonpathogens accounted for the remaining 50%. The high incidence of microorganisms in the middle ear effusions in the present series raises the possibility of bacterial contribution in many cases of OME."}
{"id": "PMID:5044", "title": "Gastro-oesophageal reflux and hiatal hernia. A re-evaluation of current data and dogma.", "content": "Various methods of investigating and treating patients with gastro-oesophageal disorders are described and the rationale of current concepts is outlined. Emphasis is placed throughout on gastro-oesophageal reflux and its sequelae rather than on sliding hiatal hernias. Symptoms of gastro-oesophageal dysfunction can be misleading, and careful studies are essential in assessing its importance and the results of various modes of therapy.", "contents": "Gastro-oesophageal reflux and hiatal hernia. A re-evaluation of current data and dogma. Various methods of investigating and treating patients with gastro-oesophageal disorders are described and the rationale of current concepts is outlined. Emphasis is placed throughout on gastro-oesophageal reflux and its sequelae rather than on sliding hiatal hernias. Symptoms of gastro-oesophageal dysfunction can be misleading, and careful studies are essential in assessing its importance and the results of various modes of therapy."}
{"id": "PMID:5046", "title": "A new look at the measurement and interpretation of enzyme assays.", "content": "Some methodological problems in clinical enzymology, including instability of enzymes in the incubation mixture and requirements for optimal reaction conditions, are highlighted. The importance of a knowledge of fundamental enzyme biochemistry and physiology as the basis for their diagnostic application is stressed, and the different behaviour of some hepatic enzymes--namely, GOT, GPT, gamma-GT, and OCT, in various pathological conditions is traced back to their characteristic biochemical and physiological properties. In the field of urinary enzymes a knowledge of the ideal requirements for the enzyme investigation of the various renal functions and of the properties of potentially valuable enzymes permits a critical selection of the really useful ones.", "contents": "A new look at the measurement and interpretation of enzyme assays. Some methodological problems in clinical enzymology, including instability of enzymes in the incubation mixture and requirements for optimal reaction conditions, are highlighted. The importance of a knowledge of fundamental enzyme biochemistry and physiology as the basis for their diagnostic application is stressed, and the different behaviour of some hepatic enzymes--namely, GOT, GPT, gamma-GT, and OCT, in various pathological conditions is traced back to their characteristic biochemical and physiological properties. In the field of urinary enzymes a knowledge of the ideal requirements for the enzyme investigation of the various renal functions and of the properties of potentially valuable enzymes permits a critical selection of the really useful ones."}
{"id": "PMID:5043", "title": "Allergic factors in management of middle ear effusions.", "content": "There is no single specific therapy for the treatment of middle ear effusions and, therefore, a holistic approach to management is necessary. Current management involves multiple therapeutic modalities of which we believe tube and allergy are most efficient.", "contents": "Allergic factors in management of middle ear effusions. There is no single specific therapy for the treatment of middle ear effusions and, therefore, a holistic approach to management is necessary. Current management involves multiple therapeutic modalities of which we believe tube and allergy are most efficient."}
{"id": "PMID:5047", "title": "[Properties of penicillin amidase covalently bound to cellulose matrices].", "content": "Properties of penicillinamidase (PA) covalently bound with the cellulose matrix were studied. The efficiency of the binding depended on the bind type and purity of the native enzyme taken for binding. Stability of the immobilized PA (IPA) was studied at wide pH ranges. The effect of the ion strength, substrate concentration and purity of the native PA on stability of IPA was also investigated. The maximum stability of the enzyme was observed at pH 6.5-7.0 Stability of IPA depended on the purity of the native enzyme. When PA of the diazotized ether of cellulose containing amino groups was used, the enzyme was destabilized. IPA prepared on chlortriazinylcellulose was more stable than the respective native PA almost by I order.", "contents": "[Properties of penicillin amidase covalently bound to cellulose matrices]. Properties of penicillinamidase (PA) covalently bound with the cellulose matrix were studied. The efficiency of the binding depended on the bind type and purity of the native enzyme taken for binding. Stability of the immobilized PA (IPA) was studied at wide pH ranges. The effect of the ion strength, substrate concentration and purity of the native PA on stability of IPA was also investigated. The maximum stability of the enzyme was observed at pH 6.5-7.0 Stability of IPA depended on the purity of the native enzyme. When PA of the diazotized ether of cellulose containing amino groups was used, the enzyme was destabilized. IPA prepared on chlortriazinylcellulose was more stable than the respective native PA almost by I order."}
{"id": "PMID:5048", "title": "[Determination of the biological activity of heliomycin by a method of diffusion in agar].", "content": "A biological method for determination of geliomycin activity using agar diffusion is described. A nutrient medium containing Hottinger broth up to 35 mg per cent of amine nitrogen, 1.5 percent of agar-agar, tap water, pH 7.8 to 8.0 was used. Bacillus subtilis ATCC 6633 served as the test-culture. Geliomycin was dissolved in 0.1 N sodium hydroxide solution.", "contents": "[Determination of the biological activity of heliomycin by a method of diffusion in agar]. A biological method for determination of geliomycin activity using agar diffusion is described. A nutrient medium containing Hottinger broth up to 35 mg per cent of amine nitrogen, 1.5 percent of agar-agar, tap water, pH 7.8 to 8.0 was used. Bacillus subtilis ATCC 6633 served as the test-culture. Geliomycin was dissolved in 0.1 N sodium hydroxide solution."}
{"id": "PMID:5049", "title": "[Study of the effect of the oxytetracycline crystallization conditions on the process indices].", "content": "Such factors as the rate of the changes in pH, temperature, mixer speed and the nature of the anions present in the solution has a significant effect on the indices of oxytetracycline dihydrate crystallization, i. e. residual content of the antibiotic in the mother solution and the specific surface of the crystalls. In this connection the effect of the above factors on the main indices of the process were studied. On the basis of the experimental data dependences were found which provided determination of the crystallization conditions securing the process indices.", "contents": "[Study of the effect of the oxytetracycline crystallization conditions on the process indices]. Such factors as the rate of the changes in pH, temperature, mixer speed and the nature of the anions present in the solution has a significant effect on the indices of oxytetracycline dihydrate crystallization, i. e. residual content of the antibiotic in the mother solution and the specific surface of the crystalls. In this connection the effect of the above factors on the main indices of the process were studied. On the basis of the experimental data dependences were found which provided determination of the crystallization conditions securing the process indices."}
{"id": "PMID:5050", "title": "[Analysis of the data in the literature on the sensitivity of cholera vibrios to tetracycline].", "content": "Variation diagrams were proposed to be used for the analysis of the published data on the study of Vibrio cholerae sensitivity to tetracycline. The diagrams provided systematization of dissimilar data of the experimental studies and a unique system of estimation was created. The analysis of the systematized data provided dividing of the Vibrio cholerae strains tested into 4 groups differing in the levels of their sensitivity to tetracycline. The groups were independent of the Vibrio cholerae biotypes and the place and period of the strain isolation.", "contents": "[Analysis of the data in the literature on the sensitivity of cholera vibrios to tetracycline]. Variation diagrams were proposed to be used for the analysis of the published data on the study of Vibrio cholerae sensitivity to tetracycline. The diagrams provided systematization of dissimilar data of the experimental studies and a unique system of estimation was created. The analysis of the systematized data provided dividing of the Vibrio cholerae strains tested into 4 groups differing in the levels of their sensitivity to tetracycline. The groups were independent of the Vibrio cholerae biotypes and the place and period of the strain isolation."}
{"id": "PMID:5051", "title": "[Toxicological characteristics of ampicillin].", "content": "Toxocity of ampicillin trihydrate was studied in acute and chronic experiments. It was shown that the antibiotic had low acute toxicity, did not cumulate and had no skin-irritating effect. On its inhalation in concentrations of 5 mg/m3 for 4 months, ampicillin induced allergization of albino rats, decreased their immunity. The general toxic effect of the drug was slightly pronounced. Ampicillin in a concentration of 0.1 mg/m3 induced tension of the immunological reactivity of the organism. The maximum permissible concentration (MPC) of ampicillin in the working premises equal to 0.1 mg/m3 is recommended. Mark \"Allergen\" is necessary.", "contents": "[Toxicological characteristics of ampicillin]. Toxocity of ampicillin trihydrate was studied in acute and chronic experiments. It was shown that the antibiotic had low acute toxicity, did not cumulate and had no skin-irritating effect. On its inhalation in concentrations of 5 mg/m3 for 4 months, ampicillin induced allergization of albino rats, decreased their immunity. The general toxic effect of the drug was slightly pronounced. Ampicillin in a concentration of 0.1 mg/m3 induced tension of the immunological reactivity of the organism. The maximum permissible concentration (MPC) of ampicillin in the working premises equal to 0.1 mg/m3 is recommended. Mark \"Allergen\" is necessary."}
{"id": "PMID:5052", "title": "Susceptibility of pneumococci and Haemophilus influenzae to antibacterial agents.", "content": "Strains of Diplococcus pneumoniae and Haemophilus influenzae were tested for susceptibility to numerous antibiotics by a twofold agar dilution method using an inocula replicator. Undiluted, fully grown broth cultures were used as inocula for both species, and cultures of pneumococci diluted 1:1,000 were also tested. The antibiotics included most of those in common use in the United States as well as some chemical modifications recently approved and others that are under investigation. The most striking aspect of the results was the marked susceptibility of the pneumococci to all the antibiotics tested except the polymyxins and most of the aminoglycoside antibiotics, although some new aminoglycosides were active in quite low concentrations. Some of the strains of pneumococci were of decreased susceptibility to penicillin G (minimal inhibitory concentrations, 0.2 to 0.4 mug/ml), but none were tetracycline resistant, although such strains had been reported previously from this laboratory. The strains of H. influenzae, which were all serologically nontypable, exhibited different patterns of susceptibility to the groups of antibiotics and to the individual chemically related ones. None of these strains (isolated early in 1972) were ampicillin resistant. The most active agents against H. influenzae were: carbenicillin and ampicillin, analogues related to each of them, rifampin, chloramphenicol, and the polymyxins. However, the tetracycline analogues other than tetracycline, some aminoglycosides, notably tobramycin, kanamycin, gentamicin, and verdamicin, erythromycin, and some new lincomycin analogues were also active in low concentrations. Trimethoprim alone was highly active, and in combination with sulfamethoxazole it was even more active and synergistic against strains of both D. pneumoniae and H. influenzae.", "contents": "Susceptibility of pneumococci and Haemophilus influenzae to antibacterial agents. Strains of Diplococcus pneumoniae and Haemophilus influenzae were tested for susceptibility to numerous antibiotics by a twofold agar dilution method using an inocula replicator. Undiluted, fully grown broth cultures were used as inocula for both species, and cultures of pneumococci diluted 1:1,000 were also tested. The antibiotics included most of those in common use in the United States as well as some chemical modifications recently approved and others that are under investigation. The most striking aspect of the results was the marked susceptibility of the pneumococci to all the antibiotics tested except the polymyxins and most of the aminoglycoside antibiotics, although some new aminoglycosides were active in quite low concentrations. Some of the strains of pneumococci were of decreased susceptibility to penicillin G (minimal inhibitory concentrations, 0.2 to 0.4 mug/ml), but none were tetracycline resistant, although such strains had been reported previously from this laboratory. The strains of H. influenzae, which were all serologically nontypable, exhibited different patterns of susceptibility to the groups of antibiotics and to the individual chemically related ones. None of these strains (isolated early in 1972) were ampicillin resistant. The most active agents against H. influenzae were: carbenicillin and ampicillin, analogues related to each of them, rifampin, chloramphenicol, and the polymyxins. However, the tetracycline analogues other than tetracycline, some aminoglycosides, notably tobramycin, kanamycin, gentamicin, and verdamicin, erythromycin, and some new lincomycin analogues were also active in low concentrations. Trimethoprim alone was highly active, and in combination with sulfamethoxazole it was even more active and synergistic against strains of both D. pneumoniae and H. influenzae."}
{"id": "PMID:5053", "title": "Comparative incidence of phlebitis due to buffered cephalothin, cephapirin, and cefamandole.", "content": "Buffered cephalothin, cefamandole, and cephapirin were compared with respect to their tendency to produce phlebitis. Two grams of each agent was administered every 6 h for 4 days to 12 healthy volunteers in a double-blind crossover fashion. Approximately 50% of intravenous sites developed mild (grade 1) phlebitis and 25% developed moderate (grade 2) phlebitis. The frequency of grade 1 inflammation did not differ significantly among the three cephalosporins. The proportion of individuals eventually exhibiting grade 2 phelebitis was highest with cefamandole, lowest with cephalothin (P = 0.07), and intermediate with cephapirin; however, cephapirin required a substantially greater number of doses to produce grade 2 phelebitis than did the other two drugs. These findings, together with the results of other reports, suggest that interpretation of the phlebitogenic potential of these antibiotics must be made with caution.", "contents": "Comparative incidence of phlebitis due to buffered cephalothin, cephapirin, and cefamandole. Buffered cephalothin, cefamandole, and cephapirin were compared with respect to their tendency to produce phlebitis. Two grams of each agent was administered every 6 h for 4 days to 12 healthy volunteers in a double-blind crossover fashion. Approximately 50% of intravenous sites developed mild (grade 1) phlebitis and 25% developed moderate (grade 2) phlebitis. The frequency of grade 1 inflammation did not differ significantly among the three cephalosporins. The proportion of individuals eventually exhibiting grade 2 phelebitis was highest with cefamandole, lowest with cephalothin (P = 0.07), and intermediate with cephapirin; however, cephapirin required a substantially greater number of doses to produce grade 2 phelebitis than did the other two drugs. These findings, together with the results of other reports, suggest that interpretation of the phlebitogenic potential of these antibiotics must be made with caution."}
{"id": "PMID:5054", "title": "Citric acid metabolism in hetero- and homofermentative lactic acid bacteria.", "content": "The effect of citrate on production of diacetyl and acetoin by four strains each of heterofermentative and homofermentative lactic acid bacteria capable of utilizing citrate was studied. Acetoin was quantitatively the more important compound. The heterofermentative bacteria produced no acetoin or diacetyl in the absence of citrate, and two strains produced traces of acetoin in its presence. Citrate stimulated the growth rate of the heterofermentative lactobacilli. Acidification of all heterofermentative cultures with citric acid resulted in acetoin production. Destruction of accumulated acetoin appeared to coincide with the disappearance of citrate. All homofermentative bacteria produced more acetoin and diacetyl in the presence of citrate than in its absence. Citrate utilization was begun immediately by the streptococci but was delayed until at least the middle of the exponential phase in the case of the lactobacilli.", "contents": "Citric acid metabolism in hetero- and homofermentative lactic acid bacteria. The effect of citrate on production of diacetyl and acetoin by four strains each of heterofermentative and homofermentative lactic acid bacteria capable of utilizing citrate was studied. Acetoin was quantitatively the more important compound. The heterofermentative bacteria produced no acetoin or diacetyl in the absence of citrate, and two strains produced traces of acetoin in its presence. Citrate stimulated the growth rate of the heterofermentative lactobacilli. Acidification of all heterofermentative cultures with citric acid resulted in acetoin production. Destruction of accumulated acetoin appeared to coincide with the disappearance of citrate. All homofermentative bacteria produced more acetoin and diacetyl in the presence of citrate than in its absence. Citrate utilization was begun immediately by the streptococci but was delayed until at least the middle of the exponential phase in the case of the lactobacilli."}
{"id": "PMID:5055", "title": "Influence of specific growth rate on biomass yield, productivity, and compostion of Candida utilis in batch and continuous culture.", "content": "Candida utilis was grown in batch and continuous culture on prickly pear juice as sole carbon and energy source. In batch culture the maximum specific growth rate (mum) and the substrate yield coefficient (Yps) varied according to sugar concentration. When the fermentation was carried out with 1% sugar, mum and Ys were 0.47/h and 42.6%, respectively. The best yields occurred in a chemostat at the pH range of 3.5 to 4.5 and temperature of 30 C. A beneficial effect on Ys was observed when the dilution rate (D) was increased. At a D of 0.55/h, the productivity was 2.38 g/liter per h. The maintenance coefficient attained a value of 0.09 g of sugar/g of biomass per h. Increases of D produced higher protein contents of the biomass. The information obtained indicates that protein production with Candida utilis, using prickly pear juice, should be carried out a high dilution rates where the Ys and protein content of the cell mass are also higher.", "contents": "Influence of specific growth rate on biomass yield, productivity, and compostion of Candida utilis in batch and continuous culture. Candida utilis was grown in batch and continuous culture on prickly pear juice as sole carbon and energy source. In batch culture the maximum specific growth rate (mum) and the substrate yield coefficient (Yps) varied according to sugar concentration. When the fermentation was carried out with 1% sugar, mum and Ys were 0.47/h and 42.6%, respectively. The best yields occurred in a chemostat at the pH range of 3.5 to 4.5 and temperature of 30 C. A beneficial effect on Ys was observed when the dilution rate (D) was increased. At a D of 0.55/h, the productivity was 2.38 g/liter per h. The maintenance coefficient attained a value of 0.09 g of sugar/g of biomass per h. Increases of D produced higher protein contents of the biomass. The information obtained indicates that protein production with Candida utilis, using prickly pear juice, should be carried out a high dilution rates where the Ys and protein content of the cell mass are also higher."}
{"id": "PMID:5056", "title": "Chemical manipulation of the heat resistance of Clostridium botulinum spores.", "content": "The chemical forms of Clostridium botulinum 62A and 213B were prepared, and their heat resistances were determined in several heating media, including some low-acid foods. The heat resistance of C. botulinum spores can be manipulated up and down by changing chemical forms between the resistant calcium form and the sensitive hydrogen form. The resistant chemical form of type B spores has about three times the classical PO4 resistance at 235 F (112.8 C). As measured in peas and asparagus, both types of C. botulinum spores came directly from the culture at only a small fraction of the potential heat resistance shown by the same spores when chemically converted to the resistant form. The resistant spore form of both types (62A and 213B), when present in a low-acid food, can be sensitized to heating at the normal pH of the food.", "contents": "Chemical manipulation of the heat resistance of Clostridium botulinum spores. The chemical forms of Clostridium botulinum 62A and 213B were prepared, and their heat resistances were determined in several heating media, including some low-acid foods. The heat resistance of C. botulinum spores can be manipulated up and down by changing chemical forms between the resistant calcium form and the sensitive hydrogen form. The resistant chemical form of type B spores has about three times the classical PO4 resistance at 235 F (112.8 C). As measured in peas and asparagus, both types of C. botulinum spores came directly from the culture at only a small fraction of the potential heat resistance shown by the same spores when chemically converted to the resistant form. The resistant spore form of both types (62A and 213B), when present in a low-acid food, can be sensitized to heating at the normal pH of the food."}
{"id": "PMID:5057", "title": "Poliovirus survival and movement in a sandy forest soil.", "content": "Movement of poliovirus I (Chat) through nonsterile core samples of a sandy forest soil was monitored, using several regimens of loading with either dechlorinated final effluent from an operating activated sludge treatment plant or distilled water. Stimulated cycles of rainfall and effluent applications, resulting in ionic gradients, were shown to affect virus movement. Such studies indicate that poliovirus applied in effluents may move considerable distances through this soil after rainfall. Survival of poliovirus in the soil at 4 and 20 C has been monitored for 84 days. During this period, the capacity of the virus to migrate is unchanged.", "contents": "Poliovirus survival and movement in a sandy forest soil. Movement of poliovirus I (Chat) through nonsterile core samples of a sandy forest soil was monitored, using several regimens of loading with either dechlorinated final effluent from an operating activated sludge treatment plant or distilled water. Stimulated cycles of rainfall and effluent applications, resulting in ionic gradients, were shown to affect virus movement. Such studies indicate that poliovirus applied in effluents may move considerable distances through this soil after rainfall. Survival of poliovirus in the soil at 4 and 20 C has been monitored for 84 days. During this period, the capacity of the virus to migrate is unchanged."}
{"id": "PMID:5058", "title": "Surface balance study of the interaction between microorganisms and lipid monolayer at the air/water interface.", "content": "Using the surface balance technique, we have compared the interaction between Acholeplasma laidlawii and some marine bacteria towards different types of monolayered lipid films. Cells from A. laidlawii and Serratia marinorubra penetrate the film, whereas cells from Psuedomonas fluorescens form a  layer underneath the film. The forces that bind microorganisms to the air/water interface are not strong enough to scatter a condensed monolayer but increase the strength of loosely packed monolayers.", "contents": "Surface balance study of the interaction between microorganisms and lipid monolayer at the air/water interface. Using the surface balance technique, we have compared the interaction between Acholeplasma laidlawii and some marine bacteria towards different types of monolayered lipid films. Cells from A. laidlawii and Serratia marinorubra penetrate the film, whereas cells from Psuedomonas fluorescens form a  layer underneath the film. The forces that bind microorganisms to the air/water interface are not strong enough to scatter a condensed monolayer but increase the strength of loosely packed monolayers."}
{"id": "PMID:5059", "title": "Toxicity of natural pyrethrins and five pyrethroids to fish.", "content": "The toxicity of natural pyrethrins and five pyrethroids was determined with coho salmon (Oncorhynchus kisutch), steelhead trout (Salmo gairdneri), fathead minnow (Pimephales promelas), channel catfish (Icatlurus punctatus), bluegill (Lepomis macrochirus), and yellow perch (Perca flavescens). The 96-hour LC50's in static tests at 12 degrees C ranged from 24.6 to 114 mug/l of natural pyrethrins and from 0.110 to 1,140 mug/l of pyrethroids. Two pyrethroids, RU-11679 and SBP-1382 (R), were over 10 times more toxic than pyrethrum extract in the flow-through tests. Coldwater species of fish were more sensitive than warmwater species to all the compunds. Temperature (12-22 degrees C) influences the toxicity of natural pyrethrin and the pyrethroids. The natural pyrethrin was more toxic to fish in pH 6.5 than in pH 9.5 water, but the toxicity of pyrethroids was not influenced in the pH range. The two most toxic pyrethroids, RU-11679 and SBP-1382, Were deactivated more rapidly in water solutions than natural pyrethrins, S-bioallethrin, dimethrin, and d-trans allethrin.", "contents": "Toxicity of natural pyrethrins and five pyrethroids to fish. The toxicity of natural pyrethrins and five pyrethroids was determined with coho salmon (Oncorhynchus kisutch), steelhead trout (Salmo gairdneri), fathead minnow (Pimephales promelas), channel catfish (Icatlurus punctatus), bluegill (Lepomis macrochirus), and yellow perch (Perca flavescens). The 96-hour LC50's in static tests at 12 degrees C ranged from 24.6 to 114 mug/l of natural pyrethrins and from 0.110 to 1,140 mug/l of pyrethroids. Two pyrethroids, RU-11679 and SBP-1382 (R), were over 10 times more toxic than pyrethrum extract in the flow-through tests. Coldwater species of fish were more sensitive than warmwater species to all the compunds. Temperature (12-22 degrees C) influences the toxicity of natural pyrethrin and the pyrethroids. The natural pyrethrin was more toxic to fish in pH 6.5 than in pH 9.5 water, but the toxicity of pyrethroids was not influenced in the pH range. The two most toxic pyrethroids, RU-11679 and SBP-1382, Were deactivated more rapidly in water solutions than natural pyrethrins, S-bioallethrin, dimethrin, and d-trans allethrin."}
{"id": "PMID:5060", "title": "Acute toxicity of selenium dioxide to freshwater fishes.", "content": "Acute toxicity tests of selenium dioxide were conducted for 96 to 336 hr in intermittent-flow bioassay systems using six species of freshwater fish. The decreasing order of species sensitivity was: fathead minnow, flagfish, brook trout, channel catfish, goldfish, and bluegil. Curves relating median lethal concentration to exposure time for each species exposed for more than 168 hr were sigmoid in shape and were characterized by a change in slope indicating a more rapid mortality rate after 96 to 168 hr toxicant exposure. The 96-hr LC50 estimates ranged from 2.9 mg/L SeO2 for fathead minnow fry to 40.0 mg/L for bluegill juveniles. Effects of brief toxicant exposure (24 hr) on fathead minnow and flagfish juveniles included limited delayed mortality and no effects on growth over a 28-day period.", "contents": "Acute toxicity of selenium dioxide to freshwater fishes. Acute toxicity tests of selenium dioxide were conducted for 96 to 336 hr in intermittent-flow bioassay systems using six species of freshwater fish. The decreasing order of species sensitivity was: fathead minnow, flagfish, brook trout, channel catfish, goldfish, and bluegil. Curves relating median lethal concentration to exposure time for each species exposed for more than 168 hr were sigmoid in shape and were characterized by a change in slope indicating a more rapid mortality rate after 96 to 168 hr toxicant exposure. The 96-hr LC50 estimates ranged from 2.9 mg/L SeO2 for fathead minnow fry to 40.0 mg/L for bluegill juveniles. Effects of brief toxicant exposure (24 hr) on fathead minnow and flagfish juveniles included limited delayed mortality and no effects on growth over a 28-day period."}
{"id": "PMID:5061", "title": "Effect of alpha and beta adrenergic blockade on epinephrine induced pulmonary insufficiency.", "content": "Recent studies demonstrated that epinephrine causes significant pulmonary A-V shunting. This study reports the effect of alpha and beta adrenergic blockade on this shunting. Sixty-three anesthetized mongrel dogs were ventilated with a mechanical respirator. Measurements of (1) the pulmonary shunt, (2) cardiac output, (3) mean pulmonary artery, pulmonary capillary wedge and systemic pressures, and (4) pulmonary and systemic vascular resistances were obtained at 5, 15 and 30 minute intervals during the first hour and hourly for 5 hours. Fifteen dogs received no treatment. All others received epinephrine hydrochloride, 2 mug/kg/min for 5 hours. Ten received epinephrine only. Ten were pretreated with propranolol hydrochloride, 250 mug/kg, 12 with phenoxybenzamine, 1 mg/kg, and 16 with phenoxybenzamine and propranolol. Propranolol significantly decreased the epinephrine induced pulmonary shunt at all times and was the most effective drug. Phenoxybenzamine decreased the early shunting, but less than propranolol, and did not decrease the late shunting. Blockade with propranolol and phenoxybenzamine was less effective than propranolol alone. Based on the observed hemodynamic changes it was suggested that beta blockade is effective in reducing epinephrine induced pulmonary insufficiency by favorably altering the flow and distribution of pulmonary blood flow which in turn decreases epinephrine induced ventilation-perfusion inequalities and capillary hypertension both of which result in shunting. Conversely phenoxybenzamine has an unfavorable effect on the pulmonary flow. These studies support previous work in animals and man which showed that beta adrenergic stimulation is important in the pathogenesis of pulmonary insufficiency. Because the amounts of epinephrine used produce blood levels observed in critical illness, these studies add support to a relationship between the increased catecholamine stimulation of critical illness and the associated and often unexplained pulmonary insufficiency.", "contents": "Effect of alpha and beta adrenergic blockade on epinephrine induced pulmonary insufficiency. Recent studies demonstrated that epinephrine causes significant pulmonary A-V shunting. This study reports the effect of alpha and beta adrenergic blockade on this shunting. Sixty-three anesthetized mongrel dogs were ventilated with a mechanical respirator. Measurements of (1) the pulmonary shunt, (2) cardiac output, (3) mean pulmonary artery, pulmonary capillary wedge and systemic pressures, and (4) pulmonary and systemic vascular resistances were obtained at 5, 15 and 30 minute intervals during the first hour and hourly for 5 hours. Fifteen dogs received no treatment. All others received epinephrine hydrochloride, 2 mug/kg/min for 5 hours. Ten received epinephrine only. Ten were pretreated with propranolol hydrochloride, 250 mug/kg, 12 with phenoxybenzamine, 1 mg/kg, and 16 with phenoxybenzamine and propranolol. Propranolol significantly decreased the epinephrine induced pulmonary shunt at all times and was the most effective drug. Phenoxybenzamine decreased the early shunting, but less than propranolol, and did not decrease the late shunting. Blockade with propranolol and phenoxybenzamine was less effective than propranolol alone. Based on the observed hemodynamic changes it was suggested that beta blockade is effective in reducing epinephrine induced pulmonary insufficiency by favorably altering the flow and distribution of pulmonary blood flow which in turn decreases epinephrine induced ventilation-perfusion inequalities and capillary hypertension both of which result in shunting. Conversely phenoxybenzamine has an unfavorable effect on the pulmonary flow. These studies support previous work in animals and man which showed that beta adrenergic stimulation is important in the pathogenesis of pulmonary insufficiency. Because the amounts of epinephrine used produce blood levels observed in critical illness, these studies add support to a relationship between the increased catecholamine stimulation of critical illness and the associated and often unexplained pulmonary insufficiency."}
{"id": "PMID:5062", "title": "Revascularization of the heart through the coronary veins.", "content": "Fifty-six dogs were used in a study to evaluate perfusion of the left anterior descending vein by the internal mammary artery in hearts with normal coronary arteries and those with ligated desending coronary arteries. Perfusion of the myocardium with arterial blood through the cardiac veins offers minimal immediate protection from infarction, as evidenced by light and electron microscopy studies. This protection is of short duration due to intimal fibrosis and luminal stenosis or obstruction of the perfused veins. Nineteen animals in which the coronary vein was perfused and the corresponding coronary artery was not ligated died within sixty hours from the time of operation. Pathological examination revealed patent grafts in all the animals. There was marked congestion of the myocardium with petechial hemorrhages over the surface of the heart. No evidence of myocardial infarction was found.", "contents": "Revascularization of the heart through the coronary veins. Fifty-six dogs were used in a study to evaluate perfusion of the left anterior descending vein by the internal mammary artery in hearts with normal coronary arteries and those with ligated desending coronary arteries. Perfusion of the myocardium with arterial blood through the cardiac veins offers minimal immediate protection from infarction, as evidenced by light and electron microscopy studies. This protection is of short duration due to intimal fibrosis and luminal stenosis or obstruction of the perfused veins. Nineteen animals in which the coronary vein was perfused and the corresponding coronary artery was not ligated died within sixty hours from the time of operation. Pathological examination revealed patent grafts in all the animals. There was marked congestion of the myocardium with petechial hemorrhages over the surface of the heart. No evidence of myocardial infarction was found."}
{"id": "PMID:5063", "title": "Dirofilaria immitis (dog heartworm) as a pulmonary lesion in humans.", "content": "Dirofilaria immitis, the dog heartworm, has been identified in the pulmonary granulomas of 5 patients from the greater Charleston area; this is the largest series of such cases from one medical center. The patients had no pulmonary symptoms. On roentgenogram the lesions were all about 2 cm in size, of uniform light opacity, and located near the pleural surface. Thoractomy was performed in each instance because of the possiblity of carcinoma. The association of granuloma formation, pulmonary infarct, and eosinophilic infiltration led to the suspicion of dirofilaria, which was confirmed in each case.", "contents": "Dirofilaria immitis (dog heartworm) as a pulmonary lesion in humans. Dirofilaria immitis, the dog heartworm, has been identified in the pulmonary granulomas of 5 patients from the greater Charleston area; this is the largest series of such cases from one medical center. The patients had no pulmonary symptoms. On roentgenogram the lesions were all about 2 cm in size, of uniform light opacity, and located near the pleural surface. Thoractomy was performed in each instance because of the possiblity of carcinoma. The association of granuloma formation, pulmonary infarct, and eosinophilic infiltration led to the suspicion of dirofilaria, which was confirmed in each case."}
{"id": "PMID:5064", "title": "Benorylate interaction with indomethacin and phenylbutazone.", "content": "The simlutaneous oral administration of benorylate (4-(acetamido) phenyl 2-acetoxybenzoate) with either indomethacin or phenylbutazone to rats suffering from Freund's adjuvant-induced arthritis leads to an anti-inflammatory effect which is significantly greater than the effect of the same drugs administered alone. Such an additive anti-inflammatory effect is not apparent when the metabolites of benorylate (paracetamol, acetylsalicylic acid) are administered with indomethacin or phenylbutazone. Paracetamol does not increase the anti-inflammatory effect of indomethacin or phenylbutazone and acetylsalicylic acid clearly antagonizes it. The molecule of benorylate itsel is therefore responsible for the additive anti-inflammatory effect. However, if antipyretic activity (yeast-induced hyperthermia) is examined instead of anti-inflammatory activity, the simultaneous oral administration of the different drugs always produces an additive effect. It is concluded that the antagonism between indomethacin or phenylbutazone and non-steroidal anti-inflammatory drugs other than benorylate is present at some receptors but not all. The clinical implications of the results are discussed.", "contents": "Benorylate interaction with indomethacin and phenylbutazone. The simlutaneous oral administration of benorylate (4-(acetamido) phenyl 2-acetoxybenzoate) with either indomethacin or phenylbutazone to rats suffering from Freund's adjuvant-induced arthritis leads to an anti-inflammatory effect which is significantly greater than the effect of the same drugs administered alone. Such an additive anti-inflammatory effect is not apparent when the metabolites of benorylate (paracetamol, acetylsalicylic acid) are administered with indomethacin or phenylbutazone. Paracetamol does not increase the anti-inflammatory effect of indomethacin or phenylbutazone and acetylsalicylic acid clearly antagonizes it. The molecule of benorylate itsel is therefore responsible for the additive anti-inflammatory effect. However, if antipyretic activity (yeast-induced hyperthermia) is examined instead of anti-inflammatory activity, the simultaneous oral administration of the different drugs always produces an additive effect. It is concluded that the antagonism between indomethacin or phenylbutazone and non-steroidal anti-inflammatory drugs other than benorylate is present at some receptors but not all. The clinical implications of the results are discussed."}
{"id": "PMID:5066", "title": "A controlled trial of amantadine in drug-induced extrapyramidal disorders.", "content": "Presently marketed antiparkinsonism drugs are potent anticholinergic agents that, while effective in treating extrapyramidal symptoms (EPS), also are productive of or can exacerbate a number of side effects associated with psychotropic drugs. Some of these include gastrointestinal disturbances, visual difficulties, and tardive dyskinesia. A double-blind study was carried out to assess the efficacy (and adverse effects) of amantadine hydrochloride--an agent without appreciable anticholinergic activity--for the treatment of drug-induced EPS. Amantadine was found to be comparable in effect to benztropine mesylate, but with fewer side effects. The potential role of amantadine may be in the treatment of patients with drug-induced EPS for whom medication with anticholinergic properties is contraindicated.", "contents": "A controlled trial of amantadine in drug-induced extrapyramidal disorders. Presently marketed antiparkinsonism drugs are potent anticholinergic agents that, while effective in treating extrapyramidal symptoms (EPS), also are productive of or can exacerbate a number of side effects associated with psychotropic drugs. Some of these include gastrointestinal disturbances, visual difficulties, and tardive dyskinesia. A double-blind study was carried out to assess the efficacy (and adverse effects) of amantadine hydrochloride--an agent without appreciable anticholinergic activity--for the treatment of drug-induced EPS. Amantadine was found to be comparable in effect to benztropine mesylate, but with fewer side effects. The potential role of amantadine may be in the treatment of patients with drug-induced EPS for whom medication with anticholinergic properties is contraindicated."}
{"id": "PMID:5067", "title": "Metabolism and ultrastructure in ovaries of alloxan-diabetic juvenile rats.", "content": "Tests were carried out on the influence of alloxan-induced diabetes mellitus on the metabolism and the ultrastructure of ovaries of juvenile rats. The diabetes mellitus caused the following changes in the metabolism: reduction in the concentration of ATP and NADPH, increase in the lactate/pyruvate quotient to above 40, reduction in the ATP/ADP quotient to below 1, reduction in the level of activity of the hydrogen-conveying enzymes G-6-P-dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase, increase in the level of activity of the alkaline phosphatase, reduction of the protein content. Ultrastructure: almost complete disappearance of the rough endoplasmic reticulum, shrinkage of the mitochondria, reduction of the cristae and condensation of the matrix. The smooth endoplasmic reticulum remains unchanged, the extent of the Golgi-complex is reduced. Easy removal of the lipid deposits.", "contents": "Metabolism and ultrastructure in ovaries of alloxan-diabetic juvenile rats. Tests were carried out on the influence of alloxan-induced diabetes mellitus on the metabolism and the ultrastructure of ovaries of juvenile rats. The diabetes mellitus caused the following changes in the metabolism: reduction in the concentration of ATP and NADPH, increase in the lactate/pyruvate quotient to above 40, reduction in the ATP/ADP quotient to below 1, reduction in the level of activity of the hydrogen-conveying enzymes G-6-P-dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase, increase in the level of activity of the alkaline phosphatase, reduction of the protein content. Ultrastructure: almost complete disappearance of the rough endoplasmic reticulum, shrinkage of the mitochondria, reduction of the cristae and condensation of the matrix. The smooth endoplasmic reticulum remains unchanged, the extent of the Golgi-complex is reduced. Easy removal of the lipid deposits."}
{"id": "PMID:5068", "title": "Human tear pH. Diurnal variations.", "content": "Using a closed chamber microelectrode system, the tear pH levels of sixteen subjects were monitored throughout the waking extent of five days. In addition to the absolute mean pH differences found among subjects, diurnal patterns of pH change could be identified for the majority. The amplitudes and periods of these cycloid patterns, however, were distinctive to each individual. Also, tear pH levels following periods of prolonged eye closure were found to be notably more acid than those associated with the waking hours.", "contents": "Human tear pH. Diurnal variations. Using a closed chamber microelectrode system, the tear pH levels of sixteen subjects were monitored throughout the waking extent of five days. In addition to the absolute mean pH differences found among subjects, diurnal patterns of pH change could be identified for the majority. The amplitudes and periods of these cycloid patterns, however, were distinctive to each individual. Also, tear pH levels following periods of prolonged eye closure were found to be notably more acid than those associated with the waking hours."}
{"id": "PMID:5069", "title": "Reactivity and ionization constants of the lysine residues in apovitellenin i of emu egg yolk low-density lipoprotein by competitive labelling.", "content": "Competitive labelling with[14C]acetic anhydride over a range of pH values has been used to explore the surface topography of the apovitellenin I moiety in emu egg yolk low-density lipoprotein. The reaction of the lysine  xi-amino groups with acetic anhydride has been related to pH in a set of titration curves; from these, the reactivities relative to alanine and the ionization constants of all but the amino terminal lysines have been determined. All lysines have near normal pKa values around 10, and lower than normal reactivities (except the amino terminal lysine). At pH values above 10, the titration curves show breaks where the epsilon-amino groups become much more reactive, except for lysine 71 which in this regard behaves like a normally ionizing lysine in not showing a discontinuity. Most of the basic residues in this apoprotein may occur clustered at the surface of the molecule. This accounts best for the observed low reactivities and pKa values. The amino terminal lysine residue is presumably completely exposed to the aqueous environment.", "contents": "Reactivity and ionization constants of the lysine residues in apovitellenin i of emu egg yolk low-density lipoprotein by competitive labelling. Competitive labelling with[14C]acetic anhydride over a range of pH values has been used to explore the surface topography of the apovitellenin I moiety in emu egg yolk low-density lipoprotein. The reaction of the lysine  xi-amino groups with acetic anhydride has been related to pH in a set of titration curves; from these, the reactivities relative to alanine and the ionization constants of all but the amino terminal lysines have been determined. All lysines have near normal pKa values around 10, and lower than normal reactivities (except the amino terminal lysine). At pH values above 10, the titration curves show breaks where the epsilon-amino groups become much more reactive, except for lysine 71 which in this regard behaves like a normally ionizing lysine in not showing a discontinuity. Most of the basic residues in this apoprotein may occur clustered at the surface of the molecule. This accounts best for the observed low reactivities and pKa values. The amino terminal lysine residue is presumably completely exposed to the aqueous environment."}
{"id": "PMID:5070", "title": "Properties and specificity of a second metal chelator-sensitive proteinase in the keratinolytic larvae of the webbing clothes moth.", "content": "The properties of a second metal chelator-sensitive proteinase (metalloproteinase 2) from the larvae of the webbing clothes moth, Tineola bisselliella, have been studied. The pH optimum for casein digestion was 9-4 and the enzyme showed high stability between pH 8 and 11, but very poor stability at acid pH. The proteinase was inhibited by EDTA, but not by an EDTA-calcium complex. EDTA inhibition could be reversed by addition of a slight excess of calcium or zinc ions. The cleavage specificity of metalloproteinase 2 against the A and B chains of S-carboxymethyl insulin was almost identical to that found previously for metalloproteinase 1.", "contents": "Properties and specificity of a second metal chelator-sensitive proteinase in the keratinolytic larvae of the webbing clothes moth. The properties of a second metal chelator-sensitive proteinase (metalloproteinase 2) from the larvae of the webbing clothes moth, Tineola bisselliella, have been studied. The pH optimum for casein digestion was 9-4 and the enzyme showed high stability between pH 8 and 11, but very poor stability at acid pH. The proteinase was inhibited by EDTA, but not by an EDTA-calcium complex. EDTA inhibition could be reversed by addition of a slight excess of calcium or zinc ions. The cleavage specificity of metalloproteinase 2 against the A and B chains of S-carboxymethyl insulin was almost identical to that found previously for metalloproteinase 1."}
{"id": "PMID:5071", "title": "Aminopeptidases in webbing clothes moth larvae. properties and specificities of enzymes of highest electrophoretic mobility.", "content": "The group of aminopeptidase bands from Tineola bisselliella larvae with highest electrophoretic mobility in polyacrylamide gels were purified further and partially separated by ion exchange chromatography. Three aminopeptidase bands were present in this material and were very similar with respect to their pH optima (7-7), their molecular weight of 94,000, their responses to metal ions and enzyme inhibitors and in their substrate specificity requirements. Kinetic constants were obtained for the hydrolysis of 17 different alpha-aminoacyl-beta-naphthylamides by these aminopeptidases, the most favoured substrates being the derivatives of alanine, methionine, proline, leucine, glycine, glutamic acid, lysine and arginine. The enzymes also hydrolyse amino acid amides, dipeptides, dipeptide amides, tripeptides and oligopeptides at the N-terminal end. These enzymes differ from the other aminopeptides in T. bisselliella in being able to hydrolyse bonds involving proline.", "contents": "Aminopeptidases in webbing clothes moth larvae. properties and specificities of enzymes of highest electrophoretic mobility. The group of aminopeptidase bands from Tineola bisselliella larvae with highest electrophoretic mobility in polyacrylamide gels were purified further and partially separated by ion exchange chromatography. Three aminopeptidase bands were present in this material and were very similar with respect to their pH optima (7-7), their molecular weight of 94,000, their responses to metal ions and enzyme inhibitors and in their substrate specificity requirements. Kinetic constants were obtained for the hydrolysis of 17 different alpha-aminoacyl-beta-naphthylamides by these aminopeptidases, the most favoured substrates being the derivatives of alanine, methionine, proline, leucine, glycine, glutamic acid, lysine and arginine. The enzymes also hydrolyse amino acid amides, dipeptides, dipeptide amides, tripeptides and oligopeptides at the N-terminal end. These enzymes differ from the other aminopeptides in T. bisselliella in being able to hydrolyse bonds involving proline."}
{"id": "PMID:5100", "title": "Anti-leukaemia activity as a bystander effect of graft-versus-host reactions.", "content": "The production of graft-versus-host (GVH) reactions in (PVGc X Wistar) F1 hybrids by the transfer of PVGc spleen cells resulted in significant resistance of these recipients to a subsequent challenge with the PVGc leukaemia. Protection was markedly dependent on dose and timing of allogeneic cell transfer and was abrogated by irradiation of the cells prior to transfer. GVH activity was shown to be a prerequisite for induction of the protective effect but was equally effective when produced by the transfer of Wistar spleen cells in place of PVGc cells. These points, plus the fact that invitro investigations of possible immune mechanisms failed to demonstrate cytotoxic immunity in treated rats, suggested a nonspecific \"bystander\" effect as the mechanism of protection. The implications of such a mechanism are discussed.", "contents": "Anti-leukaemia activity as a bystander effect of graft-versus-host reactions. The production of graft-versus-host (GVH) reactions in (PVGc X Wistar) F1 hybrids by the transfer of PVGc spleen cells resulted in significant resistance of these recipients to a subsequent challenge with the PVGc leukaemia. Protection was markedly dependent on dose and timing of allogeneic cell transfer and was abrogated by irradiation of the cells prior to transfer. GVH activity was shown to be a prerequisite for induction of the protective effect but was equally effective when produced by the transfer of Wistar spleen cells in place of PVGc cells. These points, plus the fact that invitro investigations of possible immune mechanisms failed to demonstrate cytotoxic immunity in treated rats, suggested a nonspecific \"bystander\" effect as the mechanism of protection. The implications of such a mechanism are discussed."}
{"id": "PMID:5101", "title": "The effect of aflatoxins on the incorporation of RNA and protein precursors by isolated hepatocytes.", "content": "Hepatocytes prepared by a simplified enzymatic technique were active in the incorporation of RNA and protein precursors into acid-insoluble material. The incorporation of RNA precursors was very markedly inhibited by low levels of aflatoxin B1 and G1 but not by aflatoxins B2 and G2. The activity of mixed function oxidases (MFO), the drug-metabolizing system of the endoplasmic reticulum, could be suppressed in these cells by SKF525A or stimulated by NADPH. SKF525A caused a reduction in the inhibition by aflatoxin B1 of the incorporation of RNA precursor into macromolecules. This finding suggests that a metabolite of aflatoxin B1 is the actual inhibitor of RNA synthesis in the cells. Measurement of lactate dehydrogenase activity showed these cells to be leaky on incubation at 37 degrees C and thus not suitable for studies of protein secretion.", "contents": "The effect of aflatoxins on the incorporation of RNA and protein precursors by isolated hepatocytes. Hepatocytes prepared by a simplified enzymatic technique were active in the incorporation of RNA and protein precursors into acid-insoluble material. The incorporation of RNA precursors was very markedly inhibited by low levels of aflatoxin B1 and G1 but not by aflatoxins B2 and G2. The activity of mixed function oxidases (MFO), the drug-metabolizing system of the endoplasmic reticulum, could be suppressed in these cells by SKF525A or stimulated by NADPH. SKF525A caused a reduction in the inhibition by aflatoxin B1 of the incorporation of RNA precursor into macromolecules. This finding suggests that a metabolite of aflatoxin B1 is the actual inhibitor of RNA synthesis in the cells. Measurement of lactate dehydrogenase activity showed these cells to be leaky on incubation at 37 degrees C and thus not suitable for studies of protein secretion."}
{"id": "PMID:5102", "title": "Passive serum sickness in the mouse: the role of vasoactive amines in glomerular deposition of immune complexes.", "content": "This paper reports a study of the importance of vasoactive amines in glomerular localization of passively administered immune complexes in the mouse. Two strains of mice were investigated, one sensitive and the other relatively resistant to the anaphylactogenic effect of intravenously administered immune complexes. The effect on glomerular deposition immune complexes in animals of both strains treated with either vasoactive amine depletors or antagonists leads to the conclusion that in this experimental system vasoactive amines do not play a major part in the glomerular localization of immune complexes.", "contents": "Passive serum sickness in the mouse: the role of vasoactive amines in glomerular deposition of immune complexes. This paper reports a study of the importance of vasoactive amines in glomerular localization of passively administered immune complexes in the mouse. Two strains of mice were investigated, one sensitive and the other relatively resistant to the anaphylactogenic effect of intravenously administered immune complexes. The effect on glomerular deposition immune complexes in animals of both strains treated with either vasoactive amine depletors or antagonists leads to the conclusion that in this experimental system vasoactive amines do not play a major part in the glomerular localization of immune complexes."}
{"id": "PMID:5104", "title": "Intensive care of the fetus in breech labour.", "content": "A review of 186 cases of breech presentation with a corrected perinatal mortality rate of 0-54 per cent is presented. Details of paediatric follow-up are given. Careful selection of patients for vaginal delivery and the liberal use of Caesarean section are advocated. The importance of asphyxia as the main danger of breech delivery is emphasized and the use of fetal blood sampling as a practicable method of detecting early asphyxia is discussed.", "contents": "Intensive care of the fetus in breech labour. A review of 186 cases of breech presentation with a corrected perinatal mortality rate of 0-54 per cent is presented. Details of paediatric follow-up are given. Careful selection of patients for vaginal delivery and the liberal use of Caesarean section are advocated. The importance of asphyxia as the main danger of breech delivery is emphasized and the use of fetal blood sampling as a practicable method of detecting early asphyxia is discussed."}
{"id": "PMID:5105", "title": "The effects of grass and concentrate diets on the specific activities of some enzymes of hepatic carbohydrate metabolism in sheep.", "content": "Feeding sheep a concentrate diet compared with grass diets increased the hepatic specific activities of the three glycolytic enzymes studied, and that of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and reduced the specific activity of D-fructose-I, 6-diphosphate I-phosphohydrolase (EC 3.1.3.11). The specific activities of phosphogluconate dehydrogenase (EC 1.1.1.43) and malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) were unaffected by diet.", "contents": "The effects of grass and concentrate diets on the specific activities of some enzymes of hepatic carbohydrate metabolism in sheep. Feeding sheep a concentrate diet compared with grass diets increased the hepatic specific activities of the three glycolytic enzymes studied, and that of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and reduced the specific activity of D-fructose-I, 6-diphosphate I-phosphohydrolase (EC 3.1.3.11). The specific activities of phosphogluconate dehydrogenase (EC 1.1.1.43) and malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) were unaffected by diet."}
{"id": "PMID:5106", "title": "Light-induced glutamate transport in Halobacterium halobium envelope vesicles. II. Evidence that the driving force is a light-dependent sodium gradient.", "content": "Illumination of cell envelope vesicles from H. halobium causes the development of protonmotive force and energizes the uphill transport of glutamate. Although the uncoupler, p-trifluoromethoxycarbonyl cyanide phenylhydrazone (FCCP), and the membrane-permeant cation, triphenylmethylphosphonium (TPMP+), are inhibitory to the effect of light, the time course and kinetics of the production of the energized state for transport, and its rate of decay after illumination, are inconsistent with the idea that glutamate accumulation is driven directly by the protonmotive force. Similarities between the light-induced transport and the Na+-gradient-induced transport of glutamate in these vesicles suggest that the energized state for the amino acid uptake in both cases consists of a transmembrane Na+ gradient (Na+out/Na+in greater than 1). Rapid efflux of 22Na from the envelope vesicles is induced by illumination. FCCP and TPMP+ inhibit the light-induced efflux of Na+ but accelerate the post-illumination relaxation of the Na+ gradient created, suggesting electrogenic antiport of Na+ with another cation, or electrogenic symport with an anion. The light-induced protonmotive force in the H. halobium cell envelope vesicles is thus coupled to Na+ efflux and thereby indirectly to glutamate uptake as well.", "contents": "Light-induced glutamate transport in Halobacterium halobium envelope vesicles. II. Evidence that the driving force is a light-dependent sodium gradient. Illumination of cell envelope vesicles from H. halobium causes the development of protonmotive force and energizes the uphill transport of glutamate. Although the uncoupler, p-trifluoromethoxycarbonyl cyanide phenylhydrazone (FCCP), and the membrane-permeant cation, triphenylmethylphosphonium (TPMP+), are inhibitory to the effect of light, the time course and kinetics of the production of the energized state for transport, and its rate of decay after illumination, are inconsistent with the idea that glutamate accumulation is driven directly by the protonmotive force. Similarities between the light-induced transport and the Na+-gradient-induced transport of glutamate in these vesicles suggest that the energized state for the amino acid uptake in both cases consists of a transmembrane Na+ gradient (Na+out/Na+in greater than 1). Rapid efflux of 22Na from the envelope vesicles is induced by illumination. FCCP and TPMP+ inhibit the light-induced efflux of Na+ but accelerate the post-illumination relaxation of the Na+ gradient created, suggesting electrogenic antiport of Na+ with another cation, or electrogenic symport with an anion. The light-induced protonmotive force in the H. halobium cell envelope vesicles is thus coupled to Na+ efflux and thereby indirectly to glutamate uptake as well."}
{"id": "PMID:5107", "title": "Physical studies of the nonhistone chromosomal proteins HMG-U and HMG-2.", "content": "The nonhistone chromosomal proteins, HMG-1 and HMG-2, have a folded conformation, with a high alpha-helical content, over a wide pH range. At high and low pH values, the molecules unfold. Both molecules contain cysteine and tryptophan. The tryptophans appear to be buried in the folded form. HMG-1 shows aggregation at pH 5.7, as does HMG-2 at pH 9.0. The folded form is insensitive to high concentrations of salt, suggesting that charge-charge interaction plays no role in stabilizing the tertiary structure.", "contents": "Physical studies of the nonhistone chromosomal proteins HMG-U and HMG-2. The nonhistone chromosomal proteins, HMG-1 and HMG-2, have a folded conformation, with a high alpha-helical content, over a wide pH range. At high and low pH values, the molecules unfold. Both molecules contain cysteine and tryptophan. The tryptophans appear to be buried in the folded form. HMG-1 shows aggregation at pH 5.7, as does HMG-2 at pH 9.0. The folded form is insensitive to high concentrations of salt, suggesting that charge-charge interaction plays no role in stabilizing the tertiary structure."}
{"id": "PMID:5108", "title": "Synthesis and properties of carbonylbis(methionyl)insulin, a proinsulin analogue which is convertible to insulin by cyanogen bromide cleavage.", "content": "The preparation and use of carbonylbis (L-methionine p-nitrophenyl ester) as a reversible cross-linking reagent for insulin are described. The reaction of 1 equiv of reagent with zinc insulin in dimethylformamide in the presence of triethylamine yields as one of the products NalphaA1, NepsilonB29-carbonylbis(methionyl)insulin, (CBM-insulin). The CBM-insulin was characterized by end group analysis and by the products formed on tryptic and chymotryptic cleavage. It possessed 91% of the immunological and 6.5% of the hormonal activity of insulin. Treatment of CBM-insulin with cyanogen bromide (CNBr) in 70% formic acid for 1 h resulted in nearly complete removal of the methionine bridge to yield insulin. A small amount of a side product was removed on DEAE-cellulose at pH 7.2 to give an overall recovery of insulin of 70-80%. Oxidative sulfitolyses of CBM-insulin gave the hexa(S-sulfonate) which was reduced with dithiothreitol to yield reduced CBM-insulin. The latter compound, containing 6 sulfhydryls, exhibited a pH-dependent circular dichroic spectrum. The form at pH 10 exhibited a spectrum typical of random coil which was converted to a form at pH 7.8 which was characterized by a negative extremum at 213 nm. The change in the spectrum at 213 nm with pH was characterized by an apparent pKa of 8.5. Studies on the reoxidation of reduced CBM-insulin were performed at pH values between 7.8 and 10 and at protein concentrations of 0.01-1 mg/ml. The best yields (ca. 85%) of the correctly paired disulfide bonds were obtained in reoxidations at pH 9.5-10 at protein concentration of 0.01-0.1 mg/ml. CBM-insulin, which had been isolated from reoxidation at high pH of the reduced CBM-insulin, was cleaved by CNBr to yield a fully active insulin in an overall yield of 60% from the reduced CBM-insulin.", "contents": "Synthesis and properties of carbonylbis(methionyl)insulin, a proinsulin analogue which is convertible to insulin by cyanogen bromide cleavage. The preparation and use of carbonylbis (L-methionine p-nitrophenyl ester) as a reversible cross-linking reagent for insulin are described. The reaction of 1 equiv of reagent with zinc insulin in dimethylformamide in the presence of triethylamine yields as one of the products NalphaA1, NepsilonB29-carbonylbis(methionyl)insulin, (CBM-insulin). The CBM-insulin was characterized by end group analysis and by the products formed on tryptic and chymotryptic cleavage. It possessed 91% of the immunological and 6.5% of the hormonal activity of insulin. Treatment of CBM-insulin with cyanogen bromide (CNBr) in 70% formic acid for 1 h resulted in nearly complete removal of the methionine bridge to yield insulin. A small amount of a side product was removed on DEAE-cellulose at pH 7.2 to give an overall recovery of insulin of 70-80%. Oxidative sulfitolyses of CBM-insulin gave the hexa(S-sulfonate) which was reduced with dithiothreitol to yield reduced CBM-insulin. The latter compound, containing 6 sulfhydryls, exhibited a pH-dependent circular dichroic spectrum. The form at pH 10 exhibited a spectrum typical of random coil which was converted to a form at pH 7.8 which was characterized by a negative extremum at 213 nm. The change in the spectrum at 213 nm with pH was characterized by an apparent pKa of 8.5. Studies on the reoxidation of reduced CBM-insulin were performed at pH values between 7.8 and 10 and at protein concentrations of 0.01-1 mg/ml. The best yields (ca. 85%) of the correctly paired disulfide bonds were obtained in reoxidations at pH 9.5-10 at protein concentration of 0.01-0.1 mg/ml. CBM-insulin, which had been isolated from reoxidation at high pH of the reduced CBM-insulin, was cleaved by CNBr to yield a fully active insulin in an overall yield of 60% from the reduced CBM-insulin."}
{"id": "PMID:5109", "title": "DNA-dependent RNA polymerase from the thermophilic bacterium Caldariella acidophila. Purification and basic properties of the enzyme.", "content": "A DNA-dependent RNA polymerase has been isolated from Caldariella acidophila, a thermophilic bacterium living in acidic hot springs at temperatures ranging from 63 to 89 degrees C. The enzyme was purified 180-fold and is composed of five different subunits having the following molecular weights: a = 127000, b = 120000, c = 72000, d = 65000, and e = 38000. The enzyme is activated by Mn2+ and Mg2+ and exhibits optimal activity in the presence of 0.5 mM Mn2+. The activity depends on ionic strength, with a maximum at 0.25 M KCl, and exhibits a pH optimum at 7.8 in the presence of Tris-HCl buffer. The enzyme shows a high degree of thermophilicity, its temperature optimum being 80 degrees C in the in vitro assay. The thermophilicity of C. acidophila RNA polymerase allows studies on enzyme-template interactions to be performed in a temperature range where many templates are close to their Tm.", "contents": "DNA-dependent RNA polymerase from the thermophilic bacterium Caldariella acidophila. Purification and basic properties of the enzyme. A DNA-dependent RNA polymerase has been isolated from Caldariella acidophila, a thermophilic bacterium living in acidic hot springs at temperatures ranging from 63 to 89 degrees C. The enzyme was purified 180-fold and is composed of five different subunits having the following molecular weights: a = 127000, b = 120000, c = 72000, d = 65000, and e = 38000. The enzyme is activated by Mn2+ and Mg2+ and exhibits optimal activity in the presence of 0.5 mM Mn2+. The activity depends on ionic strength, with a maximum at 0.25 M KCl, and exhibits a pH optimum at 7.8 in the presence of Tris-HCl buffer. The enzyme shows a high degree of thermophilicity, its temperature optimum being 80 degrees C in the in vitro assay. The thermophilicity of C. acidophila RNA polymerase allows studies on enzyme-template interactions to be performed in a temperature range where many templates are close to their Tm."}
{"id": "PMID:5110", "title": "Induction of stable protein-deoxyribonucleic acid adducts in Chinese hamster cell chromatin by ultraviolet light.", "content": "Ultraviolet (uv)-light-mediated formation of protein-DNA adducts in Chinese hamster cell chromatin was investigated in an attempt to compare chromatin alterations induced in vitro with those observed in vivo. Three independent methods of analysis indicated stable protein-DNA associations: (1) a membrane filter assay which retained DNA on the filter in the presence of high salt-detergent; (2) a Sepharose 4B column assay in which protein eluted cincident with DNA; and (3) a CsCl density gradient equilibrium assay which showed both protein and DNA banding at densities other than their respective native densities. Treatment of the irradiated chromatin with DNase provided further evidence that protein-DNA and not protein-protein adducts were being observed in the column assay. There is a fluence-dependent response of protein-DNA adduct formation when the chromatin is irradiated at low ionic strength and is linear for protein over the range studied. When the chromatin is exposed to differing conditions of pH, ionic strength, or divalent metal ion concentration, the quantity of adduct formed upon uv irradiation varies. Susceptibility to adduct formation can be partially explained in terms of the condensation state of the chromatin and other factors such as rearrangement, denaturation, and dissociation of the chromatin components. Besides providing information on the biological significance of these types of uv-induced lesions, this technique may be useful as a probe of chromatin structure.", "contents": "Induction of stable protein-deoxyribonucleic acid adducts in Chinese hamster cell chromatin by ultraviolet light. Ultraviolet (uv)-light-mediated formation of protein-DNA adducts in Chinese hamster cell chromatin was investigated in an attempt to compare chromatin alterations induced in vitro with those observed in vivo. Three independent methods of analysis indicated stable protein-DNA associations: (1) a membrane filter assay which retained DNA on the filter in the presence of high salt-detergent; (2) a Sepharose 4B column assay in which protein eluted cincident with DNA; and (3) a CsCl density gradient equilibrium assay which showed both protein and DNA banding at densities other than their respective native densities. Treatment of the irradiated chromatin with DNase provided further evidence that protein-DNA and not protein-protein adducts were being observed in the column assay. There is a fluence-dependent response of protein-DNA adduct formation when the chromatin is irradiated at low ionic strength and is linear for protein over the range studied. When the chromatin is exposed to differing conditions of pH, ionic strength, or divalent metal ion concentration, the quantity of adduct formed upon uv irradiation varies. Susceptibility to adduct formation can be partially explained in terms of the condensation state of the chromatin and other factors such as rearrangement, denaturation, and dissociation of the chromatin components. Besides providing information on the biological significance of these types of uv-induced lesions, this technique may be useful as a probe of chromatin structure."}
{"id": "PMID:5111", "title": "D-Mannitol dehydrogenase from Absidia glauca. Purification, metabolic role, and subunit interactions.", "content": "When Absidia glauca was grown in minimal media with D-mannitol as the only source of carbon, an NAD+ specific D-mannitol dehydrogenase (EC 1.1.1.67) was induced. The crude extract also gave evidence of mannitol kinase, mannitol-1-phosphate dehydrogenase, phosphofructokinase, and L-iditol dehydrogenase activity. The heat labile purified preparation was judged enzymically homogeneous based on evidence derived from substrate specificity studies and activity staining, following disc gel electrophoresis. The enzymic monomer, with a weight of about 67000 daltons, slowly polymerizes when stored at -20 degrees C, giving a multiplicity of protein bands on electrophoresis distributed predominantly across a spectrum from dimer to pentamer, with enzymic activity resident predominantly in even multiples of the monomer. Depolymerization occurred rapidly (hours) when a frozen preparation was brought to and held between 4 and 20 degrees C. Aggregate fragmentation with sodium dodecyl sulfate showed a time-temperature dependence, terminating in a subunit component of 13000 daltons. pH optimum for polyol oxidation occurs at 9.6 (NaOH-glycine buffer) while ketose reduction proceeded most rapidly at pH 7.0-7.2 (phosphate buffer). A regulatory role is suggested for this enzyme based on dead-end inhibition by mannitol 1-phosphate, multiple enzyme forms, and its locus at the initiation site for mannitol utilization. The physiological relevance of low-temperature aggregation to regulatory control remains to be established.", "contents": "D-Mannitol dehydrogenase from Absidia glauca. Purification, metabolic role, and subunit interactions. When Absidia glauca was grown in minimal media with D-mannitol as the only source of carbon, an NAD+ specific D-mannitol dehydrogenase (EC 1.1.1.67) was induced. The crude extract also gave evidence of mannitol kinase, mannitol-1-phosphate dehydrogenase, phosphofructokinase, and L-iditol dehydrogenase activity. The heat labile purified preparation was judged enzymically homogeneous based on evidence derived from substrate specificity studies and activity staining, following disc gel electrophoresis. The enzymic monomer, with a weight of about 67000 daltons, slowly polymerizes when stored at -20 degrees C, giving a multiplicity of protein bands on electrophoresis distributed predominantly across a spectrum from dimer to pentamer, with enzymic activity resident predominantly in even multiples of the monomer. Depolymerization occurred rapidly (hours) when a frozen preparation was brought to and held between 4 and 20 degrees C. Aggregate fragmentation with sodium dodecyl sulfate showed a time-temperature dependence, terminating in a subunit component of 13000 daltons. pH optimum for polyol oxidation occurs at 9.6 (NaOH-glycine buffer) while ketose reduction proceeded most rapidly at pH 7.0-7.2 (phosphate buffer). A regulatory role is suggested for this enzyme based on dead-end inhibition by mannitol 1-phosphate, multiple enzyme forms, and its locus at the initiation site for mannitol utilization. The physiological relevance of low-temperature aggregation to regulatory control remains to be established."}
{"id": "PMID:5112", "title": "Glutamine synthetase of Bacillus stearothermophilus. Regulation, site interactions, and functional information.", "content": "The action of various feedback modifiers on Bacillus stearothermophilus glutamine synthetase has been investigated by initial velocity kinetics, using the Mn2+-stimulated biosynthetic assay at 55 degrees C. The most potent inhibitors, used singly, are AMP, L-glutamine, and L-alanine. Other modifiers of significance include glycine, CTP, L-histidine, glucosamine 6-phosphate, and GDP. Marked synergism of action is observed for AMP in the presence of L-glutamine, L-histidine, ADP, or glucosamine 6-phosphate (glucosamine-6-P), and for CTP with ADP or GDP. Inhibition by saturating levels of many modifiers is either less than 100%, or is not overcome by elevated substrate levels, or both. This argues for modifier binding sites separate from substrate sites, notably in the cases of AMP, L-glutamine, glycine, L-alanine, glucosamine-6-P, and CTP. Glycine and L-alanine are Vmax inhibitors, whereas L-glutamine, glucosamine-6-P, GDP, and CTP alter the binding of L-glutamate. ADP and L-histidine apparently can compete directly with MnATP, but AMP alters Mn-ATP binding from a separate site. The action of several modifiers requires or is enhanced by bound substrates. Considerable antagonistic interaction is observed in experiments with modifier pairs, but the most potent inhibitors show synergistic or cumulative (independent) interactions. One may interpret antagonistic effects as due to (a) overlapping modifier domains, or (b) separate but antagonistically interacting sites. Either interpretation leads to a scheme for modifier-substrate and modifier-modifier site interactions in which the thermophilic enzyme must maintain and stabilize a great deal of complex functional information under extreme environmental conditions.", "contents": "Glutamine synthetase of Bacillus stearothermophilus. Regulation, site interactions, and functional information. The action of various feedback modifiers on Bacillus stearothermophilus glutamine synthetase has been investigated by initial velocity kinetics, using the Mn2+-stimulated biosynthetic assay at 55 degrees C. The most potent inhibitors, used singly, are AMP, L-glutamine, and L-alanine. Other modifiers of significance include glycine, CTP, L-histidine, glucosamine 6-phosphate, and GDP. Marked synergism of action is observed for AMP in the presence of L-glutamine, L-histidine, ADP, or glucosamine 6-phosphate (glucosamine-6-P), and for CTP with ADP or GDP. Inhibition by saturating levels of many modifiers is either less than 100%, or is not overcome by elevated substrate levels, or both. This argues for modifier binding sites separate from substrate sites, notably in the cases of AMP, L-glutamine, glycine, L-alanine, glucosamine-6-P, and CTP. Glycine and L-alanine are Vmax inhibitors, whereas L-glutamine, glucosamine-6-P, GDP, and CTP alter the binding of L-glutamate. ADP and L-histidine apparently can compete directly with MnATP, but AMP alters Mn-ATP binding from a separate site. The action of several modifiers requires or is enhanced by bound substrates. Considerable antagonistic interaction is observed in experiments with modifier pairs, but the most potent inhibitors show synergistic or cumulative (independent) interactions. One may interpret antagonistic effects as due to (a) overlapping modifier domains, or (b) separate but antagonistically interacting sites. Either interpretation leads to a scheme for modifier-substrate and modifier-modifier site interactions in which the thermophilic enzyme must maintain and stabilize a great deal of complex functional information under extreme environmental conditions."}
{"id": "PMID:5113", "title": "Mechanistic studies of glutamine synthetase from Escherichia coli: kinetics of ADP and orthophosphate binding to the unadenylylated enzyme.", "content": "The kinetics of protein fluorescence change exhibited by ADP or orthophosphate addition to the Mg2+-or Mn2+-activated unadenylylated glutamine synthetase from Escherichia coli were studied. The kinetic patterns of these reactions are incompatible with a simple bimolecular binding process and a mechanism which required protein isomerization prior to substrate binding. They are consistent with a mechanism in which direct substrate binding is followed by a substrate-induced conformational change step, ES in equilibrium ES. At pH 7.0 and 15 degrees C, the association constants for the direct binding (K1) of ADP to MnE1.0 and of Pi to MnE1.0ADP are 3.9 X 10(4) and 2.28 X 10(2) M(-1), respectively. The association constant for the direct binding of ADP to MnE1.0Pi is 2.3 X 10(4) M(-1) at pH 7.0 and 19 degrees C. The deltaG degrees for the substrate-induced conformational step are -3.5 and -1.3 kcal mol(-1) due to ADP binding to MnE1.0Pi and MnE1.0, respectively, and -1.4 kcal mol(-1) due to Pi binding to MnE1.0ADP. Rate constants, k2 and k(-2), for the isomerization step are: 90 and 9.5 s(-1) for ADP binding to MnE1.0, 440 and 0.36 s(-1) for ADP binding to MnE1.0Pi, and 216 and  1.8 s(-1) for Pi binding to MnE1.0ADP. Due to low substrate affinity, the association constant for direct Pi binding to MnE1.0 was roughly estimated to be 230 M(-1) and k2 = 750 s(-1), k(-2) = 250 s(-1). At 9 degrees C and pH 7.0, the estimated association constants for the direct ADP binding to MgE1.0 and MgE1.0 Pi are 1.8 X 10(4) and 1.6 X 10(4) M(-1), respectively; and the rate constants for the isomerization step associated with the corresponding reaction are k2 = 550 s(-1), k(-2) = 500 s(-1), and k2 = 210 s(-1), k(-2) = 100 s(-1). From the kinetic analysis it is evident that the inability of Mn2+ to support biosynthetic activity of the unadenylylated enzyme is due to the slow rate of ADP release from the MnE1.0PiADP complex. In contrast the large k(-2) obtained for ADP release from the MgE1.0ADP or MgE1.0PiADP complex indicates that this step is not rate limiting in the biosynthesis of glutamine since the k catalysis obtained under the same conditions is 7.2 s(-1).", "contents": "Mechanistic studies of glutamine synthetase from Escherichia coli: kinetics of ADP and orthophosphate binding to the unadenylylated enzyme. The kinetics of protein fluorescence change exhibited by ADP or orthophosphate addition to the Mg2+-or Mn2+-activated unadenylylated glutamine synthetase from Escherichia coli were studied. The kinetic patterns of these reactions are incompatible with a simple bimolecular binding process and a mechanism which required protein isomerization prior to substrate binding. They are consistent with a mechanism in which direct substrate binding is followed by a substrate-induced conformational change step, ES in equilibrium ES. At pH 7.0 and 15 degrees C, the association constants for the direct binding (K1) of ADP to MnE1.0 and of Pi to MnE1.0ADP are 3.9 X 10(4) and 2.28 X 10(2) M(-1), respectively. The association constant for the direct binding of ADP to MnE1.0Pi is 2.3 X 10(4) M(-1) at pH 7.0 and 19 degrees C. The deltaG degrees for the substrate-induced conformational step are -3.5 and -1.3 kcal mol(-1) due to ADP binding to MnE1.0Pi and MnE1.0, respectively, and -1.4 kcal mol(-1) due to Pi binding to MnE1.0ADP. Rate constants, k2 and k(-2), for the isomerization step are: 90 and 9.5 s(-1) for ADP binding to MnE1.0, 440 and 0.36 s(-1) for ADP binding to MnE1.0Pi, and 216 and  1.8 s(-1) for Pi binding to MnE1.0ADP. Due to low substrate affinity, the association constant for direct Pi binding to MnE1.0 was roughly estimated to be 230 M(-1) and k2 = 750 s(-1), k(-2) = 250 s(-1). At 9 degrees C and pH 7.0, the estimated association constants for the direct ADP binding to MgE1.0 and MgE1.0 Pi are 1.8 X 10(4) and 1.6 X 10(4) M(-1), respectively; and the rate constants for the isomerization step associated with the corresponding reaction are k2 = 550 s(-1), k(-2) = 500 s(-1), and k2 = 210 s(-1), k(-2) = 100 s(-1). From the kinetic analysis it is evident that the inability of Mn2+ to support biosynthetic activity of the unadenylylated enzyme is due to the slow rate of ADP release from the MnE1.0PiADP complex. In contrast the large k(-2) obtained for ADP release from the MgE1.0ADP or MgE1.0PiADP complex indicates that this step is not rate limiting in the biosynthesis of glutamine since the k catalysis obtained under the same conditions is 7.2 s(-1)."}
{"id": "PMID:5114", "title": "Nicotinamide adenine dinucleotide phosphate linked isocitrate dehydrogenase. Catalytic activation by the reduced coenzyme product of the reaction.", "content": "The oxidative decarboxylation of D-isocitrate catalyzed by NADP-linked isocitrate dehydrogenase is activated by NADPH, the product of the reaction. We analyzed the autocatalytic behavior exhibited by the enzyme during the steady-state kinetics. NADP acts as a competitive inhibitor toward NADPH in the catalytic activation. In a large concentration range of the reduced and oxidized coenzymes, the activity of the enzyme is proportional to the ratio (NADPH)/(NADP). The results are compared with the results of experiments done with other NADP-linked decarboxylating dehydrogenases. Two different models are presented in order to explain the mechanism of action of isocitrate dehydrogenase, according to our data.", "contents": "Nicotinamide adenine dinucleotide phosphate linked isocitrate dehydrogenase. Catalytic activation by the reduced coenzyme product of the reaction. The oxidative decarboxylation of D-isocitrate catalyzed by NADP-linked isocitrate dehydrogenase is activated by NADPH, the product of the reaction. We analyzed the autocatalytic behavior exhibited by the enzyme during the steady-state kinetics. NADP acts as a competitive inhibitor toward NADPH in the catalytic activation. In a large concentration range of the reduced and oxidized coenzymes, the activity of the enzyme is proportional to the ratio (NADPH)/(NADP). The results are compared with the results of experiments done with other NADP-linked decarboxylating dehydrogenases. Two different models are presented in order to explain the mechanism of action of isocitrate dehydrogenase, according to our data."}
{"id": "PMID:5115", "title": "Role of mannosyl lipid intermediate in the synthesis of Neurospora crassa glycoproteins.", "content": "Particulate membrane preparations from Neurospora crassa incorporated mannose from GDP-[14C] mannose into endogenous lipid and particulate protein acceptors. Synthesis of the mannosyl lipid is reversible in the presence of GDP. Chemical and chromatographic characterization of the mannosyl lipid suggest that it is a mannosylphosphorylpolyisoprenol. The other endogenous acceptor was precipitated by trichloracetic acid. Gel filtration and electrophoresis studies before and after treatment with proteolytic enzymes indicate that the second acceptor is a glycoprotein(s). beta Elimination studies on the mannosyl protein formed from GDP-[14C] mannose with Mg2+ in the reaction mixture or formed from mannosyl lipid indicate thad with the peptide chain. Several lines of evidence indicate that in Neurospora crassa the mannosyl lipid is an obligatory intermediate in the in vitro mannosylation of the protein. (a) At 15 degrees C the initial formation of the mannosyl lipid is faster than the initial formation of the mannosyl protein. (b) Exogenous partially purified mannosyl lipid can function as a mannosyl donor for the synthesis of the mannosyl protein. This reaction was also dependent on a divalent metal. The rate of this reaction was optimal at a concentration of Triton X-100 which effectively inhibited the transfer of mannose from GDP-[14C] mannose to lipid and protein, indicating that GDP-mannose was not an intermediate in the transfer of mannose from lipid to protein. The mannosyl protein formed in this reaction was indistinguishable by several criteria from the mannosyl protein formed from GDP-[14C] mannose and Mg2+. (c) The effect of a chase with an excess of unlabeled GDP-mannose on the incorporation of mannose into endogenous acceptors was immediate cessation of the synthesis and subsequent turnover of the mannosyl lipid; in contrast, however, incorporation of mannose into protein continued and was proportional to the loss of mannose from the mannosyl lipid.", "contents": "Role of mannosyl lipid intermediate in the synthesis of Neurospora crassa glycoproteins. Particulate membrane preparations from Neurospora crassa incorporated mannose from GDP-[14C] mannose into endogenous lipid and particulate protein acceptors. Synthesis of the mannosyl lipid is reversible in the presence of GDP. Chemical and chromatographic characterization of the mannosyl lipid suggest that it is a mannosylphosphorylpolyisoprenol. The other endogenous acceptor was precipitated by trichloracetic acid. Gel filtration and electrophoresis studies before and after treatment with proteolytic enzymes indicate that the second acceptor is a glycoprotein(s). beta Elimination studies on the mannosyl protein formed from GDP-[14C] mannose with Mg2+ in the reaction mixture or formed from mannosyl lipid indicate thad with the peptide chain. Several lines of evidence indicate that in Neurospora crassa the mannosyl lipid is an obligatory intermediate in the in vitro mannosylation of the protein. (a) At 15 degrees C the initial formation of the mannosyl lipid is faster than the initial formation of the mannosyl protein. (b) Exogenous partially purified mannosyl lipid can function as a mannosyl donor for the synthesis of the mannosyl protein. This reaction was also dependent on a divalent metal. The rate of this reaction was optimal at a concentration of Triton X-100 which effectively inhibited the transfer of mannose from GDP-[14C] mannose to lipid and protein, indicating that GDP-mannose was not an intermediate in the transfer of mannose from lipid to protein. The mannosyl protein formed in this reaction was indistinguishable by several criteria from the mannosyl protein formed from GDP-[14C] mannose and Mg2+. (c) The effect of a chase with an excess of unlabeled GDP-mannose on the incorporation of mannose into endogenous acceptors was immediate cessation of the synthesis and subsequent turnover of the mannosyl lipid; in contrast, however, incorporation of mannose into protein continued and was proportional to the loss of mannose from the mannosyl lipid."}
{"id": "PMID:5116", "title": "Histidine ammonia-lyase from rat liver. Purification, properties, and inhibition by substrate analogues.", "content": "Histidine ammonia-lyase (EC 4.3.1.3) from rat liver was purified more than 250-fold to near homogeneity. Electrophoretic determinations indicated a native molecular weight of approximately 200,000. The enzyme has a pH optimum of approximately pH 8.5. The minimum Km for L-histidine was 0.5 mM at pH 9.0. The Michaelis constant in the physiological pH range was, however, more than 2.0 mM. D-alpha-hydrazinoimidazolylpropionic acid was found to be a potent competitive inhibitor of liver histidine ammonia-lyase (Kis=75 muM); the L enantiomer of this compound was less effective in this regard. The enzyme was also inhibited competitively by L-histidine hydroxamate (Kis=0.4 mM), and to a lesser extent by L-histidinol, D-histidine, and glycine. Failure of a wide variety of other histidine analogues to inhibit the enzyme substantially indicates high specificity of the active site for L-histidine. No alternate substrates were identified for the enzyme. DL-alpha-Hydrazinophenylpropionic acid, the alpha-hydrzino analogue of phenylalanine, was similarly shown to be a very potent competitive inhibitor of a mechanistically similar L-phenylalanine ammonia-lyase purified from Rhodotorula glutinis. The properties of histidine ammonia-lyase from rat liver differ significantly from those of the enzyme from Pseudomonas fluorescens which has been studied most extensively to date.", "contents": "Histidine ammonia-lyase from rat liver. Purification, properties, and inhibition by substrate analogues. Histidine ammonia-lyase (EC 4.3.1.3) from rat liver was purified more than 250-fold to near homogeneity. Electrophoretic determinations indicated a native molecular weight of approximately 200,000. The enzyme has a pH optimum of approximately pH 8.5. The minimum Km for L-histidine was 0.5 mM at pH 9.0. The Michaelis constant in the physiological pH range was, however, more than 2.0 mM. D-alpha-hydrazinoimidazolylpropionic acid was found to be a potent competitive inhibitor of liver histidine ammonia-lyase (Kis=75 muM); the L enantiomer of this compound was less effective in this regard. The enzyme was also inhibited competitively by L-histidine hydroxamate (Kis=0.4 mM), and to a lesser extent by L-histidinol, D-histidine, and glycine. Failure of a wide variety of other histidine analogues to inhibit the enzyme substantially indicates high specificity of the active site for L-histidine. No alternate substrates were identified for the enzyme. DL-alpha-Hydrazinophenylpropionic acid, the alpha-hydrzino analogue of phenylalanine, was similarly shown to be a very potent competitive inhibitor of a mechanistically similar L-phenylalanine ammonia-lyase purified from Rhodotorula glutinis. The properties of histidine ammonia-lyase from rat liver differ significantly from those of the enzyme from Pseudomonas fluorescens which has been studied most extensively to date."}
{"id": "PMID:5117", "title": "Partial denaturation of mouse DNA in preparative CsCl density gradients at alkaline pH.", "content": "A new technique--partial denaturation of DNA in equilibrium CsCl density gradients at pH 11.4--is used to determine the distribution of intermediate states in the melting of mouse DNA. When the technique is applied in the preparative ultracentrifuge, the DNA is fractionated according to stability. Neutralization of the partially denatured fractions results in the recovery of most of the DNA in its native form. The individual fractions are more homogeneous than the total DNA: they have decreased density heterogeneity (smaller band widths), neutral CsCl buoyant densities that differ from the average, and more homogeneous melting profiles with melting temperatures that differ from the average.", "contents": "Partial denaturation of mouse DNA in preparative CsCl density gradients at alkaline pH. A new technique--partial denaturation of DNA in equilibrium CsCl density gradients at pH 11.4--is used to determine the distribution of intermediate states in the melting of mouse DNA. When the technique is applied in the preparative ultracentrifuge, the DNA is fractionated according to stability. Neutralization of the partially denatured fractions results in the recovery of most of the DNA in its native form. The individual fractions are more homogeneous than the total DNA: they have decreased density heterogeneity (smaller band widths), neutral CsCl buoyant densities that differ from the average, and more homogeneous melting profiles with melting temperatures that differ from the average."}
{"id": "PMID:5118", "title": "Laser Raman spectroscopic studies of the thermal unfolding of ribonuclease A.", "content": "The reversible thermal denaturation of bovine pancreatic ribonuclease A at pH 5 in 0.1 M NaCl over the range 32-70 degrees C as studied by Raman spectroscopy proceeds in a gradual manner consistent with a stepwise unfolding process rather than as a transition between two states. Conversion of residues from helical or pleated-sheet geometry to some intermediate geometry, as followed by means of the amide I and III lines, reveals that substantial amounts of the helical and pleated-sheet conformations remain at 70 degrees C. Changes in the strength of hydrogen bonding by the tyrosyl residues are indicated by the intensity ratio of the doublet at 830-850 cm(-1) and changes in the geometry of the disulfide bridges by the frequency and half-width of the Raman line near 510 cm(-1) due to the S-S vibration. Vibrations of C-S bonds in the methionines and cystines are used to monitor conformational changes in these residues. While there are small quantitative differences in temperature dependence among these probes, all agree in placing the malting temperature at or near 62 degrees C. The Raman data are quantitatively consistent with the six-stage scheme of unfolding of A.W. Burgess and H.A. Scheraga [(1975), J. Theor, Biol. 53, 403], except that no change in the environment of the tyrosines is seen until 45 degrees C.", "contents": "Laser Raman spectroscopic studies of the thermal unfolding of ribonuclease A. The reversible thermal denaturation of bovine pancreatic ribonuclease A at pH 5 in 0.1 M NaCl over the range 32-70 degrees C as studied by Raman spectroscopy proceeds in a gradual manner consistent with a stepwise unfolding process rather than as a transition between two states. Conversion of residues from helical or pleated-sheet geometry to some intermediate geometry, as followed by means of the amide I and III lines, reveals that substantial amounts of the helical and pleated-sheet conformations remain at 70 degrees C. Changes in the strength of hydrogen bonding by the tyrosyl residues are indicated by the intensity ratio of the doublet at 830-850 cm(-1) and changes in the geometry of the disulfide bridges by the frequency and half-width of the Raman line near 510 cm(-1) due to the S-S vibration. Vibrations of C-S bonds in the methionines and cystines are used to monitor conformational changes in these residues. While there are small quantitative differences in temperature dependence among these probes, all agree in placing the malting temperature at or near 62 degrees C. The Raman data are quantitatively consistent with the six-stage scheme of unfolding of A.W. Burgess and H.A. Scheraga [(1975), J. Theor, Biol. 53, 403], except that no change in the environment of the tyrosines is seen until 45 degrees C."}
{"id": "PMID:5119", "title": "Hydrogen ion titration of horse heart ferricytochrome c.", "content": "Continuous hydrogen ion titration curves of deionized solutions of horse heart ferricytochrome c have been obtained at 25 degrees C. at a constant ionic strength of 0.10 from pH 3.0 to 11.0. Titration of the oxidized protein in KCl required 28.4 equiv over that pH range, and a small hysteresis between the forward and reverse limbs was displayed. The Linderstrom-Lang approximation, which takes into account electrostatic interactions between charged groups on the protein surface, was used in a computer simulation program to analyze the forward and reverse limbs of the titration curve separately. The results indicated 1 alpha-, 12 beta- and gamma-, and 1 heme propionic carboxylic, 1 imidazole, 1 phenolic, and 18 epsilon-amino residues appear to titrate normally. Variations in the electrostatic interaction factor omega suggest conformational changes in the protein at the extremes of pH, although the relationship of the variations in omega to the magnitude of the conformational changes does not appear to be strictly quantitative for cytochrome c. These results show the acid-base behavior of cytochrome c to be complex in nature, and suggest that the Lindenstrom-Lang model may not be adequate for cytochrome c.", "contents": "Hydrogen ion titration of horse heart ferricytochrome c. Continuous hydrogen ion titration curves of deionized solutions of horse heart ferricytochrome c have been obtained at 25 degrees C. at a constant ionic strength of 0.10 from pH 3.0 to 11.0. Titration of the oxidized protein in KCl required 28.4 equiv over that pH range, and a small hysteresis between the forward and reverse limbs was displayed. The Linderstrom-Lang approximation, which takes into account electrostatic interactions between charged groups on the protein surface, was used in a computer simulation program to analyze the forward and reverse limbs of the titration curve separately. The results indicated 1 alpha-, 12 beta- and gamma-, and 1 heme propionic carboxylic, 1 imidazole, 1 phenolic, and 18 epsilon-amino residues appear to titrate normally. Variations in the electrostatic interaction factor omega suggest conformational changes in the protein at the extremes of pH, although the relationship of the variations in omega to the magnitude of the conformational changes does not appear to be strictly quantitative for cytochrome c. These results show the acid-base behavior of cytochrome c to be complex in nature, and suggest that the Lindenstrom-Lang model may not be adequate for cytochrome c."}
{"id": "PMID:5120", "title": "Isolation of brain endopeptidases: influence of size and sequence of substrates structurally related to bradykinin.", "content": "Two thiol-activated endopeptidases with pH optima near pH 7.5 were isolated from the supernatant fraction of rabbit brain homogenates by DEAE-cellulose chromatography, gel filtration and isoelectrofocusing. Peptide bond hydrolysis was measured quantitatively by ion-exchange chromatography with an amino acid analyzer. Brain kininase A hydrolyzes the Phe5-Ser6 peptide bond in bradykinin (Bk), Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9. It is isoelectric near pH 5.2 and has a molecular weight of approximately 71 000. The enzyme also hydrolyzes the Phe-Ser peptide bond in Lys-Bk, Met-Lys-Bk, des-Arg1-Bk, Lys9-Bk, Pro-Gly-Phe-Ser-Pro-Phe-Arg, and Gly-Pro-Phe-Ser-Pro-Phe-Arg, but does not hydrolyze (0.1%) this bond in des-Phe8-Arg9-Bk. Brain kininase B hydrolyzes the Pro7-Phe8 peptide bond in Bk. It is isoelectric at pH 4.9 and has a molecular weight of approximately 68 000. Brain kininase B also hydrolyzes the Pro-Phe bond in Lys-Bk, Met-Lys-Bk, Lys9-Bk, Ser-Pro-Phe-Arg, and Phe-Ser-Pro-Arg. Pretreatment of denatured kininogen with brain kininase A or B did not reduce the amount of trypsin-releasable Bk from this precursor protein, indicating that the Bk sequence, when part of a large protein, is not a substrate for either enzyme. However, kininase A and B hydrolyze the octadecapeptide Gly-Leu-Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Val-Gin-Val. The data show that a large part of the C-terminal portion of bradykinin is important for the brain kininase A activity and, for both enzymes, the size of the peptide and presumably the residues adjacent to the scissle bond are important in determining the rate of peptide bond hydrolysis by these endopeptidases.", "contents": "Isolation of brain endopeptidases: influence of size and sequence of substrates structurally related to bradykinin. Two thiol-activated endopeptidases with pH optima near pH 7.5 were isolated from the supernatant fraction of rabbit brain homogenates by DEAE-cellulose chromatography, gel filtration and isoelectrofocusing. Peptide bond hydrolysis was measured quantitatively by ion-exchange chromatography with an amino acid analyzer. Brain kininase A hydrolyzes the Phe5-Ser6 peptide bond in bradykinin (Bk), Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9. It is isoelectric near pH 5.2 and has a molecular weight of approximately 71 000. The enzyme also hydrolyzes the Phe-Ser peptide bond in Lys-Bk, Met-Lys-Bk, des-Arg1-Bk, Lys9-Bk, Pro-Gly-Phe-Ser-Pro-Phe-Arg, and Gly-Pro-Phe-Ser-Pro-Phe-Arg, but does not hydrolyze (0.1%) this bond in des-Phe8-Arg9-Bk. Brain kininase B hydrolyzes the Pro7-Phe8 peptide bond in Bk. It is isoelectric at pH 4.9 and has a molecular weight of approximately 68 000. Brain kininase B also hydrolyzes the Pro-Phe bond in Lys-Bk, Met-Lys-Bk, Lys9-Bk, Ser-Pro-Phe-Arg, and Phe-Ser-Pro-Arg. Pretreatment of denatured kininogen with brain kininase A or B did not reduce the amount of trypsin-releasable Bk from this precursor protein, indicating that the Bk sequence, when part of a large protein, is not a substrate for either enzyme. However, kininase A and B hydrolyze the octadecapeptide Gly-Leu-Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Val-Gin-Val. The data show that a large part of the C-terminal portion of bradykinin is important for the brain kininase A activity and, for both enzymes, the size of the peptide and presumably the residues adjacent to the scissle bond are important in determining the rate of peptide bond hydrolysis by these endopeptidases."}
{"id": "PMID:5121", "title": "Glucose-6-phosphate dehydrogenase from brewers' yeast. The effects of pH and temperature on the steady-state kinetic parameters of the two-chain protein species.", "content": "A systematic study has been made of the pH- and temperature-dependency of the steady-state kinetic parameters of the stabilized two-subunit enzyme species of glucose-6-phosphate dehydrogenase, in the absence of superimposed association-dissociation reactions. The Vmax(app) data obtained in several buffers between pH 5 and 10 and at 18-32 degrees C lead to the postulate that at least two sets of protonic equilibria may govern the catalysis (one near pH 5.7 AT 25 DEGREES C and another near pH 9.2); furthermore, two pathways for product formation (i.e., two Vmax's) appear to be required to explain the biphasic nature of the log Vmax(app) vs. pH curves, with Vmax(basic) greater than Vmax(acidic + neutral). Of the several buffers explored, either a uniform degree of interaction or a minimal degree of buffer species interaction could be assessed from the enthalpy changes associated with the derived values for ionization constants attributed to the protonic equilibria in the enzyme-substrates ternary complexes for the case of Tris-acetate-EDTA buffers, at constant ionic strength. With the selection of this buffer at 0.1 (T/2) and at 25 and 32 degrees C, a self-consistent kinetic mechanism has emerged which allows for the random binding of the two fully ionized substrates to the enzyme via two major pathways, and product formation by both E-A--B- and HE-A--B-. As before (Kuby et al. Arch. Biochem, Biophys. 165, 153-178, 1974), a quasi-equilibrium is presumed, with rate-limiting steps (k + 5 and k + 5') at the interconversion of the ternary complexes. Values for the two sets of protonic equilibria defined by this mechanism (viz., pKk, pKH2 for the first ionizations, and pKk', pKH' for the second) could then be estimated. From their numerical values (e.g., at 25 degrees C: pKK = 5.7 PKH2 = 5.2; and pKK' = 9.1, PKH' = 8.2) and from the values for delta H degrees ioniz (e.g., delta H degrees pKK APPROXIMATELY 5.1 KCAL/MOL; DELTA H degrees pKK' APPROXIMATELY 11 KCAL/MOL), A POSTULATE IS PRESENTED WHICH ATTRIBUTES THESE Acid dissociation constants to an imidazole and epsilon-amino group, respectively.", "contents": "Glucose-6-phosphate dehydrogenase from brewers' yeast. The effects of pH and temperature on the steady-state kinetic parameters of the two-chain protein species. A systematic study has been made of the pH- and temperature-dependency of the steady-state kinetic parameters of the stabilized two-subunit enzyme species of glucose-6-phosphate dehydrogenase, in the absence of superimposed association-dissociation reactions. The Vmax(app) data obtained in several buffers between pH 5 and 10 and at 18-32 degrees C lead to the postulate that at least two sets of protonic equilibria may govern the catalysis (one near pH 5.7 AT 25 DEGREES C and another near pH 9.2); furthermore, two pathways for product formation (i.e., two Vmax's) appear to be required to explain the biphasic nature of the log Vmax(app) vs. pH curves, with Vmax(basic) greater than Vmax(acidic + neutral). Of the several buffers explored, either a uniform degree of interaction or a minimal degree of buffer species interaction could be assessed from the enthalpy changes associated with the derived values for ionization constants attributed to the protonic equilibria in the enzyme-substrates ternary complexes for the case of Tris-acetate-EDTA buffers, at constant ionic strength. With the selection of this buffer at 0.1 (T/2) and at 25 and 32 degrees C, a self-consistent kinetic mechanism has emerged which allows for the random binding of the two fully ionized substrates to the enzyme via two major pathways, and product formation by both E-A--B- and HE-A--B-. As before (Kuby et al. Arch. Biochem, Biophys. 165, 153-178, 1974), a quasi-equilibrium is presumed, with rate-limiting steps (k + 5 and k + 5') at the interconversion of the ternary complexes. Values for the two sets of protonic equilibria defined by this mechanism (viz., pKk, pKH2 for the first ionizations, and pKk', pKH' for the second) could then be estimated. From their numerical values (e.g., at 25 degrees C: pKK = 5.7 PKH2 = 5.2; and pKK' = 9.1, PKH' = 8.2) and from the values for delta H degrees ioniz (e.g., delta H degrees pKK APPROXIMATELY 5.1 KCAL/MOL; DELTA H degrees pKK' APPROXIMATELY 11 KCAL/MOL), A POSTULATE IS PRESENTED WHICH ATTRIBUTES THESE Acid dissociation constants to an imidazole and epsilon-amino group, respectively."}
{"id": "PMID:5122", "title": "A quantitation of the factors which affect the hydrolase and transgalactosylase activities of beta-galactosidase (E. coli) on lactose.", "content": "A study was implemented to quantitate the hydrolase and transgalactosylase activities of beta-galactosidase (E. coli) with lactose as the substrate and to investigate various factors which affect these activities. At low lactose concentrations the rate of galactose production was equal to the rate of glucose production. The rate of galactose production relative to glucose, however, dropped dramatically at lactose concentrations higher than 0.05 M and production of trisaccharides and tetrasaccharides began (galactose/glucose ratios of about 2:1 and 3:1, respectively, were found for these two types of oligosaccharides). At least five different trissacharides were formed and their patterns of formation showed that they probably utilized both lactose and allolactose as galactosyl acceptors. Allolactose was produced in amounts proportional to glucose at all lactose concentrations (ratios of allolactose/glucose were about 0.88). Analyses of various data, including a reaction analyzed at very early times, showed that the major means of production of allolactose (and the only means initially) was the direct enzymatic transfer of galactose from the 4 position to the 6 position of the glucose moiety of lactose without prior release of glucose from the enzyme. It was shown, however, that allolactose could also be formed in significant quantities by the transfer of galactose to the 6 position of free glucose, and also by hydrolysis of preformed trisaccharide. A mechanism which fits the initial velocity data was proposed in which the steps involving the formation of an enzyme-gallactose-glucose complex, the formation and breakage of allolactose on the enzyme, and the release of glucose all seem to be of roughly equal magnitude and rate determining. Various factors affected the amounts of transgalactosylase and hydrolase activities occurring. At high pH values (greater than 7.8) the transgalactosylase/hydrolyase activity ratio increased dramatically while it decreased at low pH values (less than 6.0). At mid pH values the ratio was essentially constant. The absence of Mg2+ caused a large decrease in the transgalactosylase/hydrolase activity ratio while the absence of all but traces of Na+ or K+ had no effect. The anomeric configuration of lactose altered the transgalactosylase/hydrolase activity ratios, alpha-Lactose resulted in a decrease of allolactose production (transgalactosylase activity) relative to hydrolase activities (glucose production) while beta-lactose had the opposite effect.", "contents": "A quantitation of the factors which affect the hydrolase and transgalactosylase activities of beta-galactosidase (E. coli) on lactose. A study was implemented to quantitate the hydrolase and transgalactosylase activities of beta-galactosidase (E. coli) with lactose as the substrate and to investigate various factors which affect these activities. At low lactose concentrations the rate of galactose production was equal to the rate of glucose production. The rate of galactose production relative to glucose, however, dropped dramatically at lactose concentrations higher than 0.05 M and production of trisaccharides and tetrasaccharides began (galactose/glucose ratios of about 2:1 and 3:1, respectively, were found for these two types of oligosaccharides). At least five different trissacharides were formed and their patterns of formation showed that they probably utilized both lactose and allolactose as galactosyl acceptors. Allolactose was produced in amounts proportional to glucose at all lactose concentrations (ratios of allolactose/glucose were about 0.88). Analyses of various data, including a reaction analyzed at very early times, showed that the major means of production of allolactose (and the only means initially) was the direct enzymatic transfer of galactose from the 4 position to the 6 position of the glucose moiety of lactose without prior release of glucose from the enzyme. It was shown, however, that allolactose could also be formed in significant quantities by the transfer of galactose to the 6 position of free glucose, and also by hydrolysis of preformed trisaccharide. A mechanism which fits the initial velocity data was proposed in which the steps involving the formation of an enzyme-gallactose-glucose complex, the formation and breakage of allolactose on the enzyme, and the release of glucose all seem to be of roughly equal magnitude and rate determining. Various factors affected the amounts of transgalactosylase and hydrolase activities occurring. At high pH values (greater than 7.8) the transgalactosylase/hydrolyase activity ratio increased dramatically while it decreased at low pH values (less than 6.0). At mid pH values the ratio was essentially constant. The absence of Mg2+ caused a large decrease in the transgalactosylase/hydrolase activity ratio while the absence of all but traces of Na+ or K+ had no effect. The anomeric configuration of lactose altered the transgalactosylase/hydrolase activity ratios, alpha-Lactose resulted in a decrease of allolactose production (transgalactosylase activity) relative to hydrolase activities (glucose production) while beta-lactose had the opposite effect."}
{"id": "PMID:5123", "title": "The major sialoglycoprotein of the human erythrocyte membrane. Release with  a non-ionic detergent and purification.", "content": "The major sialoglycoprotein of the human erythrocyte membrane has been selectively released by the non-ionic detergent Tween 20 and further purified in detergent-free buffers by hydroxyapatite chromatography and, finally, by hydrophobic interaction chromatography on pentyl-Sepharose. The purified glycoprotein shows one main zone, PAS-1, and up to three minor zones after staining both for protein and carbohydrate in polyacrylamide gel electrophoresis in the presence of dodecyl sulfate. The relative staining intensities are concentration dependent. When the purified glycoprotein has been heated to 100 degrees C in dodecyl sulfate, more stain appears in the most rapid zone, PAS-2, and less in the slower zones, indicating a disaggregation of oligomeric forms of this glycoprotein, including a dimer, PAS-1.", "contents": "The major sialoglycoprotein of the human erythrocyte membrane. Release with  a non-ionic detergent and purification. The major sialoglycoprotein of the human erythrocyte membrane has been selectively released by the non-ionic detergent Tween 20 and further purified in detergent-free buffers by hydroxyapatite chromatography and, finally, by hydrophobic interaction chromatography on pentyl-Sepharose. The purified glycoprotein shows one main zone, PAS-1, and up to three minor zones after staining both for protein and carbohydrate in polyacrylamide gel electrophoresis in the presence of dodecyl sulfate. The relative staining intensities are concentration dependent. When the purified glycoprotein has been heated to 100 degrees C in dodecyl sulfate, more stain appears in the most rapid zone, PAS-2, and less in the slower zones, indicating a disaggregation of oligomeric forms of this glycoprotein, including a dimer, PAS-1."}
{"id": "PMID:5124", "title": "An electron paramagnetic resonance study of Mn2+ uptake by the chick chorioallantoic membrane.", "content": "Mn2+ uptake in the chick chorioallantoic membrane, an embryonic epithelial tissue which transports Ca2+ in vivo was studied using electron paramagnetic resonance (EPR). Mn2+ was used as a paramagnetic analog for Ca2+, since there is evidence that Mn2+ is accumulated by the Ca2+ transport mechanism. After 1.5 h of uptake the EPR spectrum of the Mn2+ in the membrane indicated that 89% of the Mn2+ was in a spin-exchange form, indicating close packing of Mn2+. The Mn2+ spacing was estimated from the line width to be about 4.7 A. The remaining Mn2+ was very likely Mn2+ hexahydrate. At pH 7.4 the spin-exchange spectrum tended to broaden when uptake was inhibited, while at pH 5.0 the spin-exchange spectrum was completely abolished in the presence of inhibitors. The EPR spectrum of Mn2+ in the chorioallantoic membrane had a broader line width than that of Mn2+ in isolated mitochondria, suggesting that in this tissue mitochondria are not directly involved in divalent cation transport. These EPR studies support the concept that divalent cations are sequestered in high concentrations from the rest of the cell contents during transcellular active transport.", "contents": "An electron paramagnetic resonance study of Mn2+ uptake by the chick chorioallantoic membrane. Mn2+ uptake in the chick chorioallantoic membrane, an embryonic epithelial tissue which transports Ca2+ in vivo was studied using electron paramagnetic resonance (EPR). Mn2+ was used as a paramagnetic analog for Ca2+, since there is evidence that Mn2+ is accumulated by the Ca2+ transport mechanism. After 1.5 h of uptake the EPR spectrum of the Mn2+ in the membrane indicated that 89% of the Mn2+ was in a spin-exchange form, indicating close packing of Mn2+. The Mn2+ spacing was estimated from the line width to be about 4.7 A. The remaining Mn2+ was very likely Mn2+ hexahydrate. At pH 7.4 the spin-exchange spectrum tended to broaden when uptake was inhibited, while at pH 5.0 the spin-exchange spectrum was completely abolished in the presence of inhibitors. The EPR spectrum of Mn2+ in the chorioallantoic membrane had a broader line width than that of Mn2+ in isolated mitochondria, suggesting that in this tissue mitochondria are not directly involved in divalent cation transport. These EPR studies support the concept that divalent cations are sequestered in high concentrations from the rest of the cell contents during transcellular active transport."}
{"id": "PMID:5125", "title": "Spectroscopic studies on the complex formation of suramin with bovine and human serum albumin.", "content": "The binding of suramin to bovine and human serum albumin was investigated by gel filtration and spectroscopic measurements. Besides some low-affinity binding sites suramin has, on the bovine serum albumin molecule one and on the human serum albumin molecule two, high-affinity binding sites. Spectroscopic measurements reveal that there are large differences between the albumins in the mechanism of binding to the high-affinity binding sites. Further, it is suggested that high concentrations of suramin provoke an unfolding of the albumin moleculse. In order to explain the unusual behaviour of suramin in connection with the displacement of other ligands from the albumin binding the fluorescence probe 1-anilino-8-naphthalenesulfonic acid (ANS) was employed as a reporter group molecule for fluorescence as well as circular dichroism measurements. By these measurements it could be shown that suramin greatly influences the microorganization of both albumin molecules. In the case of these measurements large differences between bovine and human serum albumin were also found.", "contents": "Spectroscopic studies on the complex formation of suramin with bovine and human serum albumin. The binding of suramin to bovine and human serum albumin was investigated by gel filtration and spectroscopic measurements. Besides some low-affinity binding sites suramin has, on the bovine serum albumin molecule one and on the human serum albumin molecule two, high-affinity binding sites. Spectroscopic measurements reveal that there are large differences between the albumins in the mechanism of binding to the high-affinity binding sites. Further, it is suggested that high concentrations of suramin provoke an unfolding of the albumin moleculse. In order to explain the unusual behaviour of suramin in connection with the displacement of other ligands from the albumin binding the fluorescence probe 1-anilino-8-naphthalenesulfonic acid (ANS) was employed as a reporter group molecule for fluorescence as well as circular dichroism measurements. By these measurements it could be shown that suramin greatly influences the microorganization of both albumin molecules. In the case of these measurements large differences between bovine and human serum albumin were also found."}
{"id": "PMID:5126", "title": "Interactions between hemoglobin and organic phosphates investigated with 31P nuclear magnetic resonance spectroscopy and ultrafiltration.", "content": "1. The chemical shifts (delta) of the phosphates of 2,3-diphosphoglycerate and adenosine triphosphate (ATP) were determined by phosphorus nuclear magnetic resonance (31P NMR) spectroscopy and were found to be displaced downfield following the addition of hemoglobin (3 mM) to a solution of either diphosphoglycerate (5 mM) or ATP (1 mM). 2. The binding of these compounds to hemoglobin was also determined by membrane ultrafiltration. A direct relationship was observed between the change in chemical shift ((delta delta) of the 2-P and 3-P of diphosphoglycerate and the percent diphosphoglycerate bound, when the latter was varied by altering pH, oxygenation state, or total diphosphoglycerate concentration. 3. In comparable studies with ATP binding, a linear relationship between the delta delta values of the gamma-, beta-, and alpha-P of ATP and the percent of ATP bound was not observed when the data from all of the experiments were plotted. NMR signals were not detectible in deoxyhemoglobin solutions containing 1 mM ATP but were seen in solutions containing 3.8 mM ATP. 4. The results indicate that 31P NMR spectroscopy is a promising tool for investigating organic phosphate interactions with hemoglobin.", "contents": "Interactions between hemoglobin and organic phosphates investigated with 31P nuclear magnetic resonance spectroscopy and ultrafiltration. 1. The chemical shifts (delta) of the phosphates of 2,3-diphosphoglycerate and adenosine triphosphate (ATP) were determined by phosphorus nuclear magnetic resonance (31P NMR) spectroscopy and were found to be displaced downfield following the addition of hemoglobin (3 mM) to a solution of either diphosphoglycerate (5 mM) or ATP (1 mM). 2. The binding of these compounds to hemoglobin was also determined by membrane ultrafiltration. A direct relationship was observed between the change in chemical shift ((delta delta) of the 2-P and 3-P of diphosphoglycerate and the percent diphosphoglycerate bound, when the latter was varied by altering pH, oxygenation state, or total diphosphoglycerate concentration. 3. In comparable studies with ATP binding, a linear relationship between the delta delta values of the gamma-, beta-, and alpha-P of ATP and the percent of ATP bound was not observed when the data from all of the experiments were plotted. NMR signals were not detectible in deoxyhemoglobin solutions containing 1 mM ATP but were seen in solutions containing 3.8 mM ATP. 4. The results indicate that 31P NMR spectroscopy is a promising tool for investigating organic phosphate interactions with hemoglobin."}
{"id": "PMID:5127", "title": "Contact-shifted resonances in the 1H NMR spectra of cytochrome b5. Resonance identification and spin density distribution in the heme group.", "content": "This paper describes the identification of some of the contact-shifted resonances in the 1H NMR spectrum of low spin ferric cytochrome b5. In these experiments comparison with cytochrome b5 which had been reconstituted with deuteroheme IX played  an important role. NMR techniques used include double resonance experiments, line width analyses, and studies of the pH-dependence of the 1H NMR chemical shifts. The electronic heme structure derived from these resonance assignments is characterized by a highly anisotropic spin density distribution. This anisotropy is most strikingly manifested in the resonances of the vinyl and propionic acid substituents of the protoheme IX. The experiments described in this paper further revealed the coexistence in aqueous solutions of two different molecular species of cytochrome b5, which can be simultaneously observed in the regions of the 1H NMR spectrum which contain the largely contact-shifted resonances.", "contents": "Contact-shifted resonances in the 1H NMR spectra of cytochrome b5. Resonance identification and spin density distribution in the heme group. This paper describes the identification of some of the contact-shifted resonances in the 1H NMR spectrum of low spin ferric cytochrome b5. In these experiments comparison with cytochrome b5 which had been reconstituted with deuteroheme IX played  an important role. NMR techniques used include double resonance experiments, line width analyses, and studies of the pH-dependence of the 1H NMR chemical shifts. The electronic heme structure derived from these resonance assignments is characterized by a highly anisotropic spin density distribution. This anisotropy is most strikingly manifested in the resonances of the vinyl and propionic acid substituents of the protoheme IX. The experiments described in this paper further revealed the coexistence in aqueous solutions of two different molecular species of cytochrome b5, which can be simultaneously observed in the regions of the 1H NMR spectrum which contain the largely contact-shifted resonances."}
{"id": "PMID:5128", "title": "Cooperative reactions of poly-L-lysine-heme complex with molecular oxygen, carbon monoxide, or cyanide ion.", "content": "The interaction of the alpha-helical poly-L-lysine-heme complex with molecular oxygen, carbon monoxide, or cyanide ion was studied. Binding equilibrium curve and activation parameters for the reactions were determined. Sigmoid responses were observed for the absorption of molecular oxygen or carbon monoxide by the complex and the cooperative parameter was found to be 2.1. This indicated a cooperative interaction between hemes situated on a cylindrical alpha-helix of poly-L-lysine. But those of other polymer-ligand-heme complexes were 1.0. The cooperative reaction mechanism, in which an alpha-helical poly-L-lysine plays an important role, was suggested.", "contents": "Cooperative reactions of poly-L-lysine-heme complex with molecular oxygen, carbon monoxide, or cyanide ion. The interaction of the alpha-helical poly-L-lysine-heme complex with molecular oxygen, carbon monoxide, or cyanide ion was studied. Binding equilibrium curve and activation parameters for the reactions were determined. Sigmoid responses were observed for the absorption of molecular oxygen or carbon monoxide by the complex and the cooperative parameter was found to be 2.1. This indicated a cooperative interaction between hemes situated on a cylindrical alpha-helix of poly-L-lysine. But those of other polymer-ligand-heme complexes were 1.0. The cooperative reaction mechanism, in which an alpha-helical poly-L-lysine plays an important role, was suggested."}
{"id": "PMID:5129", "title": "Interaction of serum albumin with normal and sickle hemoglobins.", "content": "The stability of oxyhemoglobin S during mechanical shaking was enhanced by the addition of human serum albumin. The stabilizing effect was maximum when the concentration of serum albumin approached that of oxyhemoglobin, suggesting a molecular level interaction between them. The effects of serum albumin on oxyhemoglobin A were essentially similar to those on oxyhemoglobin S. Deoxy- and methemoglobins were also stabilized by serum albumin. The addition of human serum albumin to a solution containing sickle cell oxyhemoglobin slowly formed a compound which had an absorbance peak at 620 nm. After purification by Sephadex G-200 column chromatography, this compound was identified as methemalbumin. Comparison of the rates of formation of methemalbumin from hemoglobin with various ligand states and human serum albumin showed that the rate of formation from hemichrome was much faster than from met-, oxy- and deoxyhemoglobin. About 60% of the heme was transferred from hemichrome to albumin when the mixture was kept standing at room temperature for 5 min, in contrast to only 5% from methemoglobin. This result suggests that hemichrome, rather than methemoglobin, is the intermediate in the formation of methemalbumin from oxyhemoglobin and human serum albumin. This hypothesis is supported by the finding that the rate of formation of methemalbumin was faster at alkaline pH values than at acid pH values. Serum albumin from various animal sources showed different stabilizing effects. The formation of methemalbumin from these animal albumins was far less than that from human albumin.", "contents": "Interaction of serum albumin with normal and sickle hemoglobins. The stability of oxyhemoglobin S during mechanical shaking was enhanced by the addition of human serum albumin. The stabilizing effect was maximum when the concentration of serum albumin approached that of oxyhemoglobin, suggesting a molecular level interaction between them. The effects of serum albumin on oxyhemoglobin A were essentially similar to those on oxyhemoglobin S. Deoxy- and methemoglobins were also stabilized by serum albumin. The addition of human serum albumin to a solution containing sickle cell oxyhemoglobin slowly formed a compound which had an absorbance peak at 620 nm. After purification by Sephadex G-200 column chromatography, this compound was identified as methemalbumin. Comparison of the rates of formation of methemalbumin from hemoglobin with various ligand states and human serum albumin showed that the rate of formation from hemichrome was much faster than from met-, oxy- and deoxyhemoglobin. About 60% of the heme was transferred from hemichrome to albumin when the mixture was kept standing at room temperature for 5 min, in contrast to only 5% from methemoglobin. This result suggests that hemichrome, rather than methemoglobin, is the intermediate in the formation of methemalbumin from oxyhemoglobin and human serum albumin. This hypothesis is supported by the finding that the rate of formation of methemalbumin was faster at alkaline pH values than at acid pH values. Serum albumin from various animal sources showed different stabilizing effects. The formation of methemalbumin from these animal albumins was far less than that from human albumin."}
{"id": "PMID:5130", "title": "On the separation of fibrinogen degradation products D and E.", "content": "Separation of fibrinogen degradation products D and E by means of gel chromatography cannot be achieved at neutral pH even in the presence of high ionic strength of the elution buffer. It is assumed that fragments D and E are linked together in a complex preventing the separation despite different molecular weights of both components. By means of addition of chaotropic substances like 1 M Kl to the elution buffer clear separation of degradation products D and E on Sephadex G-200 columns can be achieved.", "contents": "On the separation of fibrinogen degradation products D and E. Separation of fibrinogen degradation products D and E by means of gel chromatography cannot be achieved at neutral pH even in the presence of high ionic strength of the elution buffer. It is assumed that fragments D and E are linked together in a complex preventing the separation despite different molecular weights of both components. By means of addition of chaotropic substances like 1 M Kl to the elution buffer clear separation of degradation products D and E on Sephadex G-200 columns can be achieved."}
{"id": "PMID:5131", "title": "Affinity chromatography on hydroxyalkyl methacrylate gels. III. Adsorption of chymotrypsin to poly(hydroxyalkyl methacrylates) with covalently bound benzyloxycarbonyl-glycyl-D-phenylalanine and -D-leucine as function of pH and ionic strength.", "content": "Chymotrypsin is specifically adsorbed at low ionic strength and alkaline pH to hydroxyalkyl methacrylate gels with N-benzyloxycarbonylglycl-D-phenylalanine or N-benzyloxycarbonylglycyl-D-leucine attached through 1,6-hexanediamine. Chymotrypsin is not adsorbed either to the unmodified gel (Spheron) or to the gel with attached, 1,6-hexanediamine (NH2-Spheron). The adsorption of chymotrypsin to Z-Gly-D-Phe-NH2-Spheron was investigated as a function of pH and ionic strength. Trypsin is not adsorbed to this gel. Chymotrypsin isolated from a crude pancreatic extract by affinity chromatography on Z-Gly-D-Phe-NH2-Spheron had the same activity as the enzyme isolated on a column of Spheron, to which the naturally-occurring trypsin inhibitor had been coupled.", "contents": "Affinity chromatography on hydroxyalkyl methacrylate gels. III. Adsorption of chymotrypsin to poly(hydroxyalkyl methacrylates) with covalently bound benzyloxycarbonyl-glycyl-D-phenylalanine and -D-leucine as function of pH and ionic strength. Chymotrypsin is specifically adsorbed at low ionic strength and alkaline pH to hydroxyalkyl methacrylate gels with N-benzyloxycarbonylglycl-D-phenylalanine or N-benzyloxycarbonylglycyl-D-leucine attached through 1,6-hexanediamine. Chymotrypsin is not adsorbed either to the unmodified gel (Spheron) or to the gel with attached, 1,6-hexanediamine (NH2-Spheron). The adsorption of chymotrypsin to Z-Gly-D-Phe-NH2-Spheron was investigated as a function of pH and ionic strength. Trypsin is not adsorbed to this gel. Chymotrypsin isolated from a crude pancreatic extract by affinity chromatography on Z-Gly-D-Phe-NH2-Spheron had the same activity as the enzyme isolated on a column of Spheron, to which the naturally-occurring trypsin inhibitor had been coupled."}
{"id": "PMID:5132", "title": "Heme-linked proton dissociation of carbon monoxide complexes of myoglobin and peroxidase.", "content": "It was found from spectrophotometric titration and proton balance measurement that the pKa value of a heme-linked protonation group of horseradish ferro-peroxidase C (donor:H2O2 oxidoreductase, EC 1.11.1.7) shifted from 7.25 to 8.25 upon combination with CO. The spectrophotometric titration experiment with myoglobin also revealed the presence of a heme-linked protonation group, the pKa value being 5.57 in myoglobin and 5.67 in the CO-myoglobin complex. It was concluded that the distinct shift of the pKa value in the case of peroxidase was attributable to the presence of a hydrogen bond between the sixth ligand and the distal base. The difference in the strength of such hydrogen bonding between peroxidase and myoglobin was discussed.", "contents": "Heme-linked proton dissociation of carbon monoxide complexes of myoglobin and peroxidase. It was found from spectrophotometric titration and proton balance measurement that the pKa value of a heme-linked protonation group of horseradish ferro-peroxidase C (donor:H2O2 oxidoreductase, EC 1.11.1.7) shifted from 7.25 to 8.25 upon combination with CO. The spectrophotometric titration experiment with myoglobin also revealed the presence of a heme-linked protonation group, the pKa value being 5.57 in myoglobin and 5.67 in the CO-myoglobin complex. It was concluded that the distinct shift of the pKa value in the case of peroxidase was attributable to the presence of a hydrogen bond between the sixth ligand and the distal base. The difference in the strength of such hydrogen bonding between peroxidase and myoglobin was discussed."}
{"id": "PMID:5133", "title": "Isolation, characterization and partial sequence of cyanogen bromide fragments and thiol peptides from pig kidney D-amino-acid oxidase.", "content": "A partial characterization of the primary structure of D-amino-acid oxidase (D-Amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3.) from hog kidney has been achieved by a CNBr cleavage of the 14C-carboxymethylated protein. Four fragments have been isolated and purified and their alignment made possible by overlapping with methionine-containing peptides derived from tryptic digestion of the 14C-carboxymethylated protein. A partial sequencing of the CNBr fragments has been carried out by the automated Edman procedure and by manual sequence analysis. Chymotryptic peptides containing the 5 alkylated thiols of the monomer enzyme (Curti, B., Ronchi, S., branzoli, U., Ferri, G. and Williams, Jr., C. H. (1973) Biochim. Biophys. Acta 327, 266-273) have been isolated and their sequence determined. The present results do not show any significant homologies with the known sequences of other flavoproteins.", "contents": "Isolation, characterization and partial sequence of cyanogen bromide fragments and thiol peptides from pig kidney D-amino-acid oxidase. A partial characterization of the primary structure of D-amino-acid oxidase (D-Amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3.) from hog kidney has been achieved by a CNBr cleavage of the 14C-carboxymethylated protein. Four fragments have been isolated and purified and their alignment made possible by overlapping with methionine-containing peptides derived from tryptic digestion of the 14C-carboxymethylated protein. A partial sequencing of the CNBr fragments has been carried out by the automated Edman procedure and by manual sequence analysis. Chymotryptic peptides containing the 5 alkylated thiols of the monomer enzyme (Curti, B., Ronchi, S., branzoli, U., Ferri, G. and Williams, Jr., C. H. (1973) Biochim. Biophys. Acta 327, 266-273) have been isolated and their sequence determined. The present results do not show any significant homologies with the known sequences of other flavoproteins."}
{"id": "PMID:5134", "title": "The fluorescence decay of tryptophan residues in native and denatured proteins.", "content": "The fluorescence decay kinetics at different ranges of the emission spectrum is reported for 17 proteins. Out of eight proteins containing a single tryptophan residue per molecule, seven proteins display multiexponential decay kinetics, suggesting that variability in protein structure may exist for most proteins. Tryptophan residues whose fluorescence spectrum is red shifted may have lifetimes longer than 7 ns. Such long lifetimes have not been detected in any of the denatured proteins studied, indicating that in native proteins the tryptophans having a red-shifted spectrum are affected by the tertiary structure of the protein. The fluorescence decay kinetics of ten denatured proteins studied obey multiexponential decay functions. It is therefore concluded that the tryptophan residues in denatured proteins can be grouped in two classes. The first characterized by a relatively long lifetime of about 4 ns and the second has a short lifetime of about 1.5 ns. The emission spectrum of the group which is characterized by the longer lifetime is red shifted relative to the emission spectrum of the group characterized by the shorter lifetime. A comparison of the decay data with the quantum yield of the proteins raises the possibility that a subgroup of the tryptophan residues is fully quenched. It is noteworthy that despite this heterogeneity in  the environment of tryptophan residues in each denatured protein, almost the same decay kinetics has been obtained for all the denatured proteins studied in spite of the vastly different primary structures. It is therefore concluded that each tryptophan residue interacts in a more-or-less random manner with other groups on the polypeptide chain, and that on the average the different tryptophan residues in denatured proteins have a similar type of environment.", "contents": "The fluorescence decay of tryptophan residues in native and denatured proteins. The fluorescence decay kinetics at different ranges of the emission spectrum is reported for 17 proteins. Out of eight proteins containing a single tryptophan residue per molecule, seven proteins display multiexponential decay kinetics, suggesting that variability in protein structure may exist for most proteins. Tryptophan residues whose fluorescence spectrum is red shifted may have lifetimes longer than 7 ns. Such long lifetimes have not been detected in any of the denatured proteins studied, indicating that in native proteins the tryptophans having a red-shifted spectrum are affected by the tertiary structure of the protein. The fluorescence decay kinetics of ten denatured proteins studied obey multiexponential decay functions. It is therefore concluded that the tryptophan residues in denatured proteins can be grouped in two classes. The first characterized by a relatively long lifetime of about 4 ns and the second has a short lifetime of about 1.5 ns. The emission spectrum of the group which is characterized by the longer lifetime is red shifted relative to the emission spectrum of the group characterized by the shorter lifetime. A comparison of the decay data with the quantum yield of the proteins raises the possibility that a subgroup of the tryptophan residues is fully quenched. It is noteworthy that despite this heterogeneity in  the environment of tryptophan residues in each denatured protein, almost the same decay kinetics has been obtained for all the denatured proteins studied in spite of the vastly different primary structures. It is therefore concluded that each tryptophan residue interacts in a more-or-less random manner with other groups on the polypeptide chain, and that on the average the different tryptophan residues in denatured proteins have a similar type of environment."}
{"id": "PMID:5135", "title": "Endogenous proteolytic activity and constituent polypeptide chains of sheep and pig 19 S thyroglobulin.", "content": "Porcine and ovine 19-S thyroglobulins prepared from frozen glands in several buffers using slice extraction or homogenization, ammonium sulfate precipitation and DEAE-cellulose chromatography or Sepharose 6B gel filtration were contaminated with protease activity of pH optima 4.5 and 8.6, as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Optimum temperatures of autodigestion were 37 degrees C at pH 4.5 and 25 degrees C at pH 8.6. Thyroglobulins prepared from unfrozen glands pH 7.2 in 0.1 M sodium phosphate using slice extraction, ammonium sulfate precipitation and Sepharose 6B gel filtration were devoid of acid proteolytic activity but still underwent autodigestion at pH 8.6. Diisopropylfluorophosphate was a potent inhibitor of the alkaline protease activity of ovine thyroglobulin preparations. In contrast to thyroglobulin obtained from frozen glands the proteins purified from fresh unfrozen glands at pH 7.2 only showed the 19-S and the 12-S species by electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Very few bands migrating faster than 12-S were visible. After full reduction and S-alkylation of porcine and ovine thyroglobulins, no qualitative changes were observed in the gel electrophoresis pattern as compared to the unmodified proteins. Species of apparent mol. wt. corresponding to the native 12 S were the major component, strongly suggesting a mol. wt. of about 330 000 for the elementary peptide chains of pig and sheep thyroglobulins.", "contents": "Endogenous proteolytic activity and constituent polypeptide chains of sheep and pig 19 S thyroglobulin. Porcine and ovine 19-S thyroglobulins prepared from frozen glands in several buffers using slice extraction or homogenization, ammonium sulfate precipitation and DEAE-cellulose chromatography or Sepharose 6B gel filtration were contaminated with protease activity of pH optima 4.5 and 8.6, as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Optimum temperatures of autodigestion were 37 degrees C at pH 4.5 and 25 degrees C at pH 8.6. Thyroglobulins prepared from unfrozen glands pH 7.2 in 0.1 M sodium phosphate using slice extraction, ammonium sulfate precipitation and Sepharose 6B gel filtration were devoid of acid proteolytic activity but still underwent autodigestion at pH 8.6. Diisopropylfluorophosphate was a potent inhibitor of the alkaline protease activity of ovine thyroglobulin preparations. In contrast to thyroglobulin obtained from frozen glands the proteins purified from fresh unfrozen glands at pH 7.2 only showed the 19-S and the 12-S species by electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Very few bands migrating faster than 12-S were visible. After full reduction and S-alkylation of porcine and ovine thyroglobulins, no qualitative changes were observed in the gel electrophoresis pattern as compared to the unmodified proteins. Species of apparent mol. wt. corresponding to the native 12 S were the major component, strongly suggesting a mol. wt. of about 330 000 for the elementary peptide chains of pig and sheep thyroglobulins."}
{"id": "PMID:5136", "title": "The existence of three types of acetohydroxy acid synthetase in an isoleucine-requiring mutant of Aerobacter aerogenes.", "content": "The synthesis of the three types of acetolactate synthase (EC 4.1.3.18) which are responsible for the biosynthesis os isoleucine and valine, was observed in Aerobacter aerogenes I-12, an isoleucine-requiring mutant, when grown on the four kinds of media. When the cells were grown on isoleucine-rich medium, acetolactate synthase sensitive to feedback inhibition and having an optimum pH at 8.0 was formed. By increasing the amount of potassium phosphate in the medium, the catabolite repression of the enzyme having an optimum pH at 6.0 and which is insensitive to feedback inhibition, was released. In contrast, acetolactate synthase having an optimum pH at 8.0 and insensitive to feedback inhibition was formd when isoleucine was limited, irrespective of phosphate concentrations. Two insensitive enzymes were not regulated by isoleucine, leucine and valine, although sensitive pH 8.0 enzyme was repressed by them. Thus, it may be assumed that the synthesis of insensitive pH 8.0 enzyme were repressed by limiting the amount of isoleucine is still open.", "contents": "The existence of three types of acetohydroxy acid synthetase in an isoleucine-requiring mutant of Aerobacter aerogenes. The synthesis of the three types of acetolactate synthase (EC 4.1.3.18) which are responsible for the biosynthesis os isoleucine and valine, was observed in Aerobacter aerogenes I-12, an isoleucine-requiring mutant, when grown on the four kinds of media. When the cells were grown on isoleucine-rich medium, acetolactate synthase sensitive to feedback inhibition and having an optimum pH at 8.0 was formed. By increasing the amount of potassium phosphate in the medium, the catabolite repression of the enzyme having an optimum pH at 6.0 and which is insensitive to feedback inhibition, was released. In contrast, acetolactate synthase having an optimum pH at 8.0 and insensitive to feedback inhibition was formd when isoleucine was limited, irrespective of phosphate concentrations. Two insensitive enzymes were not regulated by isoleucine, leucine and valine, although sensitive pH 8.0 enzyme was repressed by them. Thus, it may be assumed that the synthesis of insensitive pH 8.0 enzyme were repressed by limiting the amount of isoleucine is still open."}
{"id": "PMID:5137", "title": "Identification of the chemical groups involved in the binding of periodate-oxidized NADP+ to 6-phosphogluconate dehydrogenase.", "content": "Periodate-oxidized NADP+ binds specifically and reversibly to the NADP+ binding site of 6-phosphogluconate dehydrogenase (EC 1.1.1.44) from Candida utilis. The inhibition can be stabilized by reduction with sodium borohydride. It has been shown that an aldehydic group of the inhibitor forms a Schiff base with a lysine residue of the enzyme.", "contents": "Identification of the chemical groups involved in the binding of periodate-oxidized NADP+ to 6-phosphogluconate dehydrogenase. Periodate-oxidized NADP+ binds specifically and reversibly to the NADP+ binding site of 6-phosphogluconate dehydrogenase (EC 1.1.1.44) from Candida utilis. The inhibition can be stabilized by reduction with sodium borohydride. It has been shown that an aldehydic group of the inhibitor forms a Schiff base with a lysine residue of the enzyme."}
{"id": "PMID:5138", "title": "Studies on inosine monophosphate dehydrogenase. Isotope exchange at equilibrium.", "content": "Investigations on the mechanism of the IMP dehydrogenase (IMP: NAD+ oxidoreductase, EC 1.2.1.14) reactions have been made at pH 7.0 by measuring rates of isotope exchange at chemical equilibrium with K+ maintained at a constant concentration. The results are generally in accord with the conclusions reached on the basis of the steady-state kinetic data obtained previously and confirm that there is random addition of IMP and NAD to the enzyme. The data also indicate clearly that at pH 7.0 catalysis is faster than the rate of IMP and/or XMP release which is rate limiting for the reaction sequence. The binding of IMP to the enzyme at pH 8.1 has been demonstrated to occur in the absence of both K+ and NAD and id independent of the K+ concentration.", "contents": "Studies on inosine monophosphate dehydrogenase. Isotope exchange at equilibrium. Investigations on the mechanism of the IMP dehydrogenase (IMP: NAD+ oxidoreductase, EC 1.2.1.14) reactions have been made at pH 7.0 by measuring rates of isotope exchange at chemical equilibrium with K+ maintained at a constant concentration. The results are generally in accord with the conclusions reached on the basis of the steady-state kinetic data obtained previously and confirm that there is random addition of IMP and NAD to the enzyme. The data also indicate clearly that at pH 7.0 catalysis is faster than the rate of IMP and/or XMP release which is rate limiting for the reaction sequence. The binding of IMP to the enzyme at pH 8.1 has been demonstrated to occur in the absence of both K+ and NAD and id independent of the K+ concentration."}
{"id": "PMID:5139", "title": "Oxidation of N-methyl substituted hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives by bovine milk xanthine oxidase.", "content": "1. The oxidation of six series of purines (hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives) by a highly purified bovine milk xanthine oxidase (EC 1.2.3.2) has been studied, using a variety of N-methyl derivatives. 2. N-Methyl substituents can either enhance or reduce enzymic rates. Enhancement is ascribed to blockade of groups which mediate unfavorable modes of binding of substrate to enzyme. Introduction of N-methyl groups can also inhibit enzymic oxidation, either by occluding essential binding groups or by preventing spontaneous or enzyme-induced tautomerisation processes, which create suitable binding sites in the substrates. 3. In all purines which are rapidly attacked by xanthine oxidase, proper attachment to the active center is mediated by the groupings (3) NH, (9) N or (3) N, (9) NH. 4. Reduced rates usually express lowered substrate affinity, which finds its expression in weak competitive inhibition of xanthine oxidation.", "contents": "Oxidation of N-methyl substituted hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives by bovine milk xanthine oxidase. 1. The oxidation of six series of purines (hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives) by a highly purified bovine milk xanthine oxidase (EC 1.2.3.2) has been studied, using a variety of N-methyl derivatives. 2. N-Methyl substituents can either enhance or reduce enzymic rates. Enhancement is ascribed to blockade of groups which mediate unfavorable modes of binding of substrate to enzyme. Introduction of N-methyl groups can also inhibit enzymic oxidation, either by occluding essential binding groups or by preventing spontaneous or enzyme-induced tautomerisation processes, which create suitable binding sites in the substrates. 3. In all purines which are rapidly attacked by xanthine oxidase, proper attachment to the active center is mediated by the groupings (3) NH, (9) N or (3) N, (9) NH. 4. Reduced rates usually express lowered substrate affinity, which finds its expression in weak competitive inhibition of xanthine oxidation."}
{"id": "PMID:5140", "title": "Multiple forms of histone acetyltransferases in the cytosol of calf endometrium.", "content": "The histone acetyltransferase (EC 2.3.1.-) activity of calf endometrium cytosol has been separated into three separate activities by stepwise chromatography on DEAE-cellulose. In addition to differential elution from the DEAE-cellulose, the three activities are differentiated by their pH optima, preferences for histone subfractions as substrates, and stability to heat denaturation. Peak I has an optimum of pH 8.7 and preferentially acetylates histones F2b and F3; Peak II has an optimum of pH 8.5, and preferentially acetylates histone F2al followed by histone F2b; Peak III has an optimum of pH 9.5, and had similar specificity to Peak II. Peak III is appreciably more stable at 60 degrees C than is Peak II. None of the peaks transferred acetate to other proteins tested or to tRNA. These studies suggest the presence of multiple histone acetyltransferases in tissue cytosols.", "contents": "Multiple forms of histone acetyltransferases in the cytosol of calf endometrium. The histone acetyltransferase (EC 2.3.1.-) activity of calf endometrium cytosol has been separated into three separate activities by stepwise chromatography on DEAE-cellulose. In addition to differential elution from the DEAE-cellulose, the three activities are differentiated by their pH optima, preferences for histone subfractions as substrates, and stability to heat denaturation. Peak I has an optimum of pH 8.7 and preferentially acetylates histones F2b and F3; Peak II has an optimum of pH 8.5, and preferentially acetylates histone F2al followed by histone F2b; Peak III has an optimum of pH 9.5, and had similar specificity to Peak II. Peak III is appreciably more stable at 60 degrees C than is Peak II. None of the peaks transferred acetate to other proteins tested or to tRNA. These studies suggest the presence of multiple histone acetyltransferases in tissue cytosols."}
{"id": "PMID:5141", "title": "Purification and characterization of butyrylcholine-hydrolyzing enzyme from Pseudomonas polycolor.", "content": "A butyrylcholine-hydrolyzing enzyme (EC 3.1.1.-) fo Pseudomonas polycolor IFO 3918 was purified approximately 9270-fold with a recovery of 9.9% by use of chromatographic techniques. The enzyme preparation appeared to be homogeneous when subjected to electrophoretic and ultracentrifugational analyses. The molecular weight was determined as approximately 59000 by gel filtration. Isoelectric focusing electrophoresis revealed that the enzyme had an isoelectric point around pH 5.1. The enzyme catalyzed the hydrolysis of butyrylcholine with the miximum activity among various esters tested, and split benzoylcholine, propionylcholine and some aliphatic esters, but did not attact acetylcholine. The estimated value of Km at pH 7.5 and 25 degrees C was 7-10(-4) M for butyrylcholine. The enzyme was irreversibly inhibited by organophosphorus compounds and carbamates, such as diisopropylphosphofluoridate and eserine. The enzyme was inhibited by some compounds, such as atropine and quinidine. Auaternary ammonium salts showed an inhibitory effect on the enzyme resembling co-operative inhibition.", "contents": "Purification and characterization of butyrylcholine-hydrolyzing enzyme from Pseudomonas polycolor. A butyrylcholine-hydrolyzing enzyme (EC 3.1.1.-) fo Pseudomonas polycolor IFO 3918 was purified approximately 9270-fold with a recovery of 9.9% by use of chromatographic techniques. The enzyme preparation appeared to be homogeneous when subjected to electrophoretic and ultracentrifugational analyses. The molecular weight was determined as approximately 59000 by gel filtration. Isoelectric focusing electrophoresis revealed that the enzyme had an isoelectric point around pH 5.1. The enzyme catalyzed the hydrolysis of butyrylcholine with the miximum activity among various esters tested, and split benzoylcholine, propionylcholine and some aliphatic esters, but did not attact acetylcholine. The estimated value of Km at pH 7.5 and 25 degrees C was 7-10(-4) M for butyrylcholine. The enzyme was irreversibly inhibited by organophosphorus compounds and carbamates, such as diisopropylphosphofluoridate and eserine. The enzyme was inhibited by some compounds, such as atropine and quinidine. Auaternary ammonium salts showed an inhibitory effect on the enzyme resembling co-operative inhibition."}
{"id": "PMID:5142", "title": "A phospholipase A2 with anticoagulant activity. I. Isolation from Vipera berus venom and properties.", "content": "An anticoagulant protein has been isolated by DEAE cellulose chromatography and gel filtration from the venom of the Vipera berus orientale (Eastern Europe). Purification has been completed by elution on carboxymethyl cellulose with continuous gradient at constant pH. The inhibitor of coagulation was separated from the other venom enzymes, e.g. procoagulant, fibrinogenolytic, aminoesterase and amino acid oxidase activities. It was also separated from other phospholipase components which were not related to the anticoagulant property. The inhibitor appeared as a simgle polypeptidic chain protein, formed by 119 amino acid residues, with a molecular weight of 13400 and an isoelectric point of 9.2. At low saline molarity, a monomer-trimer transition of this protein was observed. Both forms had the same amino acid composition. There were six disulfide bridges without free SH groups per phospholipase molecule. Deprived of any proteolytic activity, the clotting inhibitor displayed a high phospholipase activity in the presence of calcium. Activity did no appear with EDTA buffer deprived of cation. Finely dispersed micellar suspensions were found suitable for obtaining the highest phospholipase activity. High sodium cholate concentration or methanol/chloroform/ether solvent were effective without loss of enzymatic activity. As characteristis of phospholipase A2 (EC 3.1.1.4), the degradation products identified on thin-layer chromatography induced hemolysis of human erythrocytes. The apparent Km value 1.25 - 10(-3) M was determined on phosphatidylcholine isolated from ovolecithin. This purified berus inhibitor would be of value for investigating the involvement of phospholipids in the clotting mechanism.", "contents": "A phospholipase A2 with anticoagulant activity. I. Isolation from Vipera berus venom and properties. An anticoagulant protein has been isolated by DEAE cellulose chromatography and gel filtration from the venom of the Vipera berus orientale (Eastern Europe). Purification has been completed by elution on carboxymethyl cellulose with continuous gradient at constant pH. The inhibitor of coagulation was separated from the other venom enzymes, e.g. procoagulant, fibrinogenolytic, aminoesterase and amino acid oxidase activities. It was also separated from other phospholipase components which were not related to the anticoagulant property. The inhibitor appeared as a simgle polypeptidic chain protein, formed by 119 amino acid residues, with a molecular weight of 13400 and an isoelectric point of 9.2. At low saline molarity, a monomer-trimer transition of this protein was observed. Both forms had the same amino acid composition. There were six disulfide bridges without free SH groups per phospholipase molecule. Deprived of any proteolytic activity, the clotting inhibitor displayed a high phospholipase activity in the presence of calcium. Activity did no appear with EDTA buffer deprived of cation. Finely dispersed micellar suspensions were found suitable for obtaining the highest phospholipase activity. High sodium cholate concentration or methanol/chloroform/ether solvent were effective without loss of enzymatic activity. As characteristis of phospholipase A2 (EC 3.1.1.4), the degradation products identified on thin-layer chromatography induced hemolysis of human erythrocytes. The apparent Km value 1.25 - 10(-3) M was determined on phosphatidylcholine isolated from ovolecithin. This purified berus inhibitor would be of value for investigating the involvement of phospholipids in the clotting mechanism."}
{"id": "PMID:5143", "title": "A phospholipase A2 with anticoagulant activity. II. Inhibition of the phospholiped activity in coagulation.", "content": "An anticoagulant factor with phospholipase A2 activity has been isolated from Vipera berus venom. Phospholipase activity was studied on platelet phospholipid and on brain cephalin. The venom factor showed a potent anticoagulant activity: 1 mug impaired the clotting of 1 ml of citrated recalcified platelet-poor plasma. The anticoagulant inhibited clotting by antagonism to phospholipid. The antagonism constant (Kan = 6.8-10(-9) M) demonstrated the high affinity of the inhibitor for phospholipid. As with other phospholipases A2, the venom factor was thermoresistant but very sensitive to photo-oxidation. Both activities (anticoagulant activity and phospholipase activity) were not markedly dissociated by either denaturation or neutralization processes. Slightly different curves of photo-oxidative inactivation of both activities suggested the presence, on the molecule, of two very close sites responsible for phospholipase and anticoagulant activities. The inhibitor effect on coagulation was independent of the hydrolysis process. In fact, lysoderivatives and fatty acids, resulting from complete hydrolysis with the venom factor, were as active as the native phospholipids. Moreover phospholipase A2 from other viperidae venom, which did not have anticoagulant activity, produced similarly active lysoderivatives. This showed that the cleavage of the beta-acyl bond does not interfere with the activity of phospholipid. A possible mechanism of clotting inhibition by the venom factor was proposed. Owing to its high affinity for phospholipid, the inhibitor would complex phospholipid at its protein binding site impairing the normal arrangement of coagulation protein factors and, consequently, their activation. The positive charges of the inhibitor (pI = 9.2) could bind with phosphoryl or carboxyl groups of phospholipid, making them unavailable for protein binding. The complex formation involves a loss of dissociating capacity of the enzyme towards its substrate. This required an additional interaction of the inhibitor with a coagulation protein factor. The inhibitor could be removed from the complex by specific antibodies, permitting recovery of normal phospholipid-protein interaction. The role of calcium in the complex has not yet been elucidated. This venom factor affords a useful tool for investigating the phospholipid-clotting protein interaction.", "contents": "A phospholipase A2 with anticoagulant activity. II. Inhibition of the phospholiped activity in coagulation. An anticoagulant factor with phospholipase A2 activity has been isolated from Vipera berus venom. Phospholipase activity was studied on platelet phospholipid and on brain cephalin. The venom factor showed a potent anticoagulant activity: 1 mug impaired the clotting of 1 ml of citrated recalcified platelet-poor plasma. The anticoagulant inhibited clotting by antagonism to phospholipid. The antagonism constant (Kan = 6.8-10(-9) M) demonstrated the high affinity of the inhibitor for phospholipid. As with other phospholipases A2, the venom factor was thermoresistant but very sensitive to photo-oxidation. Both activities (anticoagulant activity and phospholipase activity) were not markedly dissociated by either denaturation or neutralization processes. Slightly different curves of photo-oxidative inactivation of both activities suggested the presence, on the molecule, of two very close sites responsible for phospholipase and anticoagulant activities. The inhibitor effect on coagulation was independent of the hydrolysis process. In fact, lysoderivatives and fatty acids, resulting from complete hydrolysis with the venom factor, were as active as the native phospholipids. Moreover phospholipase A2 from other viperidae venom, which did not have anticoagulant activity, produced similarly active lysoderivatives. This showed that the cleavage of the beta-acyl bond does not interfere with the activity of phospholipid. A possible mechanism of clotting inhibition by the venom factor was proposed. Owing to its high affinity for phospholipid, the inhibitor would complex phospholipid at its protein binding site impairing the normal arrangement of coagulation protein factors and, consequently, their activation. The positive charges of the inhibitor (pI = 9.2) could bind with phosphoryl or carboxyl groups of phospholipid, making them unavailable for protein binding. The complex formation involves a loss of dissociating capacity of the enzyme towards its substrate. This required an additional interaction of the inhibitor with a coagulation protein factor. The inhibitor could be removed from the complex by specific antibodies, permitting recovery of normal phospholipid-protein interaction. The role of calcium in the complex has not yet been elucidated. This venom factor affords a useful tool for investigating the phospholipid-clotting protein interaction."}
{"id": "PMID:5144", "title": "Steady-state enzyme kinetics of the pancreatic ribonucleases from five mannalian species.", "content": "The kinetic parameters Km, k+2 and k+2/Km of the pancreatic ribonucleases (EC 3.1.4.22) from cow, giraffe, horse, rat and lesser rorqual have been determined, using 2',3'-cyclic cytidine monophosphate and 2',3'-cuclic uridine monophosphate as substrates. No large differences were found between the activities of the five enzymes. The relative differences between the activities of the five enzymes are mainly due to differences in the rates of hydrolysis and not to differences in the affinities for the substrates.", "contents": "Steady-state enzyme kinetics of the pancreatic ribonucleases from five mannalian species. The kinetic parameters Km, k+2 and k+2/Km of the pancreatic ribonucleases (EC 3.1.4.22) from cow, giraffe, horse, rat and lesser rorqual have been determined, using 2',3'-cyclic cytidine monophosphate and 2',3'-cuclic uridine monophosphate as substrates. No large differences were found between the activities of the five enzymes. The relative differences between the activities of the five enzymes are mainly due to differences in the rates of hydrolysis and not to differences in the affinities for the substrates."}
{"id": "PMID:5145", "title": "Alpha-D-Mannosidase. Preparation and properties of free and insolubilized enzyme.", "content": "Alpha-D-Mannosidase (alpha-D-mannoside mannohydrolase, EC 3.2.1.24) has been purified to homogeneity as demonstrated by polyacrylamide gel electrophoresis and ultracentrifugation. The molecular weight of the enzyme is approx. 200000; the protein appears to contain 4 subunits, with molecular weights of 66000 and 44000. The enzyme was immobilized on Sepharose and the properties of the coupled and free enzyme were compared. Both were stable up to 70 degrees C with rapid loss of activity between 75-80 degrees C; both retained 25-30% activity in 6 M urea and 65% of the original activity could be restored in the coupled preparation by removal of the urea. The pH maximum of each form was approximately the same, with the maximum of the immobilized enzyme shifted slightly to a lower pH. The coupled alpha-D-mannosidase presented in this report offers the possibility of digesting high molecular weight substrates, such as glycoproteins, with the advantages of (1) recovering large quantities of digested substrate; (2) recovery of the active glycosidase; and (3) digestion at high temperatures and under conditions that denature many proteins.", "contents": "Alpha-D-Mannosidase. Preparation and properties of free and insolubilized enzyme. Alpha-D-Mannosidase (alpha-D-mannoside mannohydrolase, EC 3.2.1.24) has been purified to homogeneity as demonstrated by polyacrylamide gel electrophoresis and ultracentrifugation. The molecular weight of the enzyme is approx. 200000; the protein appears to contain 4 subunits, with molecular weights of 66000 and 44000. The enzyme was immobilized on Sepharose and the properties of the coupled and free enzyme were compared. Both were stable up to 70 degrees C with rapid loss of activity between 75-80 degrees C; both retained 25-30% activity in 6 M urea and 65% of the original activity could be restored in the coupled preparation by removal of the urea. The pH maximum of each form was approximately the same, with the maximum of the immobilized enzyme shifted slightly to a lower pH. The coupled alpha-D-mannosidase presented in this report offers the possibility of digesting high molecular weight substrates, such as glycoproteins, with the advantages of (1) recovering large quantities of digested substrate; (2) recovery of the active glycosidase; and (3) digestion at high temperatures and under conditions that denature many proteins."}
{"id": "PMID:5146", "title": "Isolation and partial characterization of a protease from Agave americana variegata.", "content": "A new protease was isolated from an extract of leaves of Agave americana variegata. The protease (EC 3.4.-) was purified 565-fold with a yield of 39.5%. The 43.8 mg enzyme had a specific activity of 0.44 units/mg. According to electrophoretic, ultracentrifugal and other physical characterizations the enzyme was homogeneous. The enzyme had a MR of 57000, a S20,W-value of 4.37 S, a D20, W-value of 6.8-7.0 - 10(-7) cm2sec-1, a Stokes radius of 3.18 nm, a partial specific volume of 0.735 cm3g-1, a frictional ration of 1.25, a molecular absorbancy index at 280 nm of 5.773-10(4), an isoelectric point of 5.25 and contained 8-10% carbohydrate. The enzyme contained no cysteine. Agave protease could hydrolyze a variety of protein substrates although it did have a restricted specificity. It is not a sulphhydryl protease but seems to be an alkaline \"serine\" protease with an optimum pH of 7.8-8.0 Agave protease had marked esterolytic activity and with Cbz-Tyr-ONp had an apparent Michaelis constant of 0.0345 -10(-3) M and a V of 1.24 mol substrate/mol enzyme per sec. The enzyme did not need metal ions for optimal activity, monovalent cations did not influence its kinetic parameters, but it was inhibited by cobalt, pC1HgBzO- and TosPheCH2C1. With respect to its primary specificity, as well as its pH-dependence there was a resemblance with chymotrypsin, although the rate of hydrolysis of Agave protease is much lower.", "contents": "Isolation and partial characterization of a protease from Agave americana variegata. A new protease was isolated from an extract of leaves of Agave americana variegata. The protease (EC 3.4.-) was purified 565-fold with a yield of 39.5%. The 43.8 mg enzyme had a specific activity of 0.44 units/mg. According to electrophoretic, ultracentrifugal and other physical characterizations the enzyme was homogeneous. The enzyme had a MR of 57000, a S20,W-value of 4.37 S, a D20, W-value of 6.8-7.0 - 10(-7) cm2sec-1, a Stokes radius of 3.18 nm, a partial specific volume of 0.735 cm3g-1, a frictional ration of 1.25, a molecular absorbancy index at 280 nm of 5.773-10(4), an isoelectric point of 5.25 and contained 8-10% carbohydrate. The enzyme contained no cysteine. Agave protease could hydrolyze a variety of protein substrates although it did have a restricted specificity. It is not a sulphhydryl protease but seems to be an alkaline \"serine\" protease with an optimum pH of 7.8-8.0 Agave protease had marked esterolytic activity and with Cbz-Tyr-ONp had an apparent Michaelis constant of 0.0345 -10(-3) M and a V of 1.24 mol substrate/mol enzyme per sec. The enzyme did not need metal ions for optimal activity, monovalent cations did not influence its kinetic parameters, but it was inhibited by cobalt, pC1HgBzO- and TosPheCH2C1. With respect to its primary specificity, as well as its pH-dependence there was a resemblance with chymotrypsin, although the rate of hydrolysis of Agave protease is much lower."}
{"id": "PMID:5147", "title": "Yeast aminopeptidase I. Chemical composition and catalytic properties.", "content": "An aminopeptidase (alpha-aminoacyl L-peptide hydrolase, EC 3.4.11.1) was purified to homogeneity from autolysates of brewer's yeast. The enzyme which is responsible for most of the yeast cell's aminopeptidase activity is a glycoprotein containing about 12% of conjugated carbohydrate and 0.02% Zn2+ and having a complex quaternary structure. The active species has a molecular weight of approx. 600000 and an isoelectric point of 4.7. The enzyme is remarkably stable, even in dilute solutions. All types of L-amino acid and peptide derivatives containing a free amino terminus are attacked, including amino acid amides and esters. As to its substrate specificity, the enzyme belongs to the so called leucine-aminopeptidases. It is strongly and specifically activated by Zn2+ and Cl- (or Br-) and inactivated by metal-chelating agents. The activation by Zn2+ seems to be mediated by a conformational transition which affects exclusively V and leads to a form of the enzyme which enhanced stability against heat. Halide anions, on the other hand, are acting as positive allosteric effectors, modulating both V and Km.", "contents": "Yeast aminopeptidase I. Chemical composition and catalytic properties. An aminopeptidase (alpha-aminoacyl L-peptide hydrolase, EC 3.4.11.1) was purified to homogeneity from autolysates of brewer's yeast. The enzyme which is responsible for most of the yeast cell's aminopeptidase activity is a glycoprotein containing about 12% of conjugated carbohydrate and 0.02% Zn2+ and having a complex quaternary structure. The active species has a molecular weight of approx. 600000 and an isoelectric point of 4.7. The enzyme is remarkably stable, even in dilute solutions. All types of L-amino acid and peptide derivatives containing a free amino terminus are attacked, including amino acid amides and esters. As to its substrate specificity, the enzyme belongs to the so called leucine-aminopeptidases. It is strongly and specifically activated by Zn2+ and Cl- (or Br-) and inactivated by metal-chelating agents. The activation by Zn2+ seems to be mediated by a conformational transition which affects exclusively V and leads to a form of the enzyme which enhanced stability against heat. Halide anions, on the other hand, are acting as positive allosteric effectors, modulating both V and Km."}
{"id": "PMID:5148", "title": "Preparation and enzymatic properties of subtilisin Novo chemically attached to soluble DEAE-dextran and insoluble DEAE-sephadex.", "content": "Analogous soluble and insoluble derivatives of subtilisin Novo (EC 3.4.21.14) were prepared by coupling the enzyme to CNBr-activated DEAE-dextran and DEAE-Sephadex, respectively. The DEAE-dextran-subtilisin displayed pH optima and Km values for ester hydrolysis similar to subtilisin, whereas the pH versus activity profiles obtained with DEAE-Sephadex-subtilisin were shifter towards the alkaline pH region and the Km values were increased. Compared with subtilisin, DEAE-dextran-subtilisin showed a 40-65% reduction of kcat for hydrolysis of N-acetyl-L-tyrosine ethyl ester, p-tosyl-L-arginine methyl ester and benzyloxycarbonyl-glycyl-L-tyrosinamide and its maximum velocities for digestion of casein and clupein also amounted to 40-60% of the subtilisin values. With Deae-sephadex-subtilisin, in contrast, the maximum velocity of hydrolysis decreased to a greater extent for polypeptide substrates compared to ester substrates. The present results indicate that the chemical nature of a support can effect intrinsic properties of a matrix-bound enzyme in addition to the steric and diffusional effects usually observed with polymer-attached enzymes.", "contents": "Preparation and enzymatic properties of subtilisin Novo chemically attached to soluble DEAE-dextran and insoluble DEAE-sephadex. Analogous soluble and insoluble derivatives of subtilisin Novo (EC 3.4.21.14) were prepared by coupling the enzyme to CNBr-activated DEAE-dextran and DEAE-Sephadex, respectively. The DEAE-dextran-subtilisin displayed pH optima and Km values for ester hydrolysis similar to subtilisin, whereas the pH versus activity profiles obtained with DEAE-Sephadex-subtilisin were shifter towards the alkaline pH region and the Km values were increased. Compared with subtilisin, DEAE-dextran-subtilisin showed a 40-65% reduction of kcat for hydrolysis of N-acetyl-L-tyrosine ethyl ester, p-tosyl-L-arginine methyl ester and benzyloxycarbonyl-glycyl-L-tyrosinamide and its maximum velocities for digestion of casein and clupein also amounted to 40-60% of the subtilisin values. With Deae-sephadex-subtilisin, in contrast, the maximum velocity of hydrolysis decreased to a greater extent for polypeptide substrates compared to ester substrates. The present results indicate that the chemical nature of a support can effect intrinsic properties of a matrix-bound enzyme in addition to the steric and diffusional effects usually observed with polymer-attached enzymes."}
{"id": "PMID:5149", "title": "Photocontrol of urease-collagen membrane activity.", "content": "(1) Urease (EC 3.5.1.5.) was modified with beta-1-[3,3-dimethyl-6'-nitrospiro-(indoline-2,2'-2H-benzopyrene)] propionic anhydride. Three amino acid residues of urease were modified by the anhydride at a molar ratio of 2000. (2) The activity of modified urease was decreased with ultraviolet irradiation and then restored to the initial activity with visible light irradiation. (3) Modified urease was used to prepare a urease-collagen membrane. The apparent Michaelis constant (Km) of the modified urease-collagen membrane ultraviolet light was identical to that of the membrane under visible light. (4) The optimum pH of the modified urease-collagen membrane was displaced toward lower pH values with ultraviolet irradiation. At higher ionic strength, the pH activity curve of the membrane was displaced toward higher pH values. (5) The thermostability of urease was increased with its modification.", "contents": "Photocontrol of urease-collagen membrane activity. (1) Urease (EC 3.5.1.5.) was modified with beta-1-[3,3-dimethyl-6'-nitrospiro-(indoline-2,2'-2H-benzopyrene)] propionic anhydride. Three amino acid residues of urease were modified by the anhydride at a molar ratio of 2000. (2) The activity of modified urease was decreased with ultraviolet irradiation and then restored to the initial activity with visible light irradiation. (3) Modified urease was used to prepare a urease-collagen membrane. The apparent Michaelis constant (Km) of the modified urease-collagen membrane ultraviolet light was identical to that of the membrane under visible light. (4) The optimum pH of the modified urease-collagen membrane was displaced toward lower pH values with ultraviolet irradiation. At higher ionic strength, the pH activity curve of the membrane was displaced toward higher pH values. (5) The thermostability of urease was increased with its modification."}
{"id": "PMID:5150", "title": "Fluoride inhibition of inorganic pyrophosphatase. I. Kinetic studies in a Mg2+-PPi system using a new continuous enzyme assay.", "content": "Reversible inhibition of bakers' yeast inorganic pyrophosphatase (EC 3.6.1.1) by fluoride has been studied as a function of substrate, metal-ion activator and inhibitor concentrations and pH using a new continuous enzyme assay with an automatic phosphate analyzer. The inhibition was shown to be the result of tight binding of fluoride by two catalytically active enzyme-substrate complexes. The reaction between pyrophosphatase and fluoride is relatively slow, so that the rate constants for the binding and release of the inhibitor were derived from phosphate formation curves measured on the time scale of enzyme assays. The pH-dependence of the inhibition reaction in the alkaline medium indicates that both the fluoride-enzyme interaction and the catalytic step of the pyrophosphatase reaction are controlled by the same group on the protein. In the acidic medium, the inhibition is considerably enhanced, presumably because of the protonation of another enzyme group.", "contents": "Fluoride inhibition of inorganic pyrophosphatase. I. Kinetic studies in a Mg2+-PPi system using a new continuous enzyme assay. Reversible inhibition of bakers' yeast inorganic pyrophosphatase (EC 3.6.1.1) by fluoride has been studied as a function of substrate, metal-ion activator and inhibitor concentrations and pH using a new continuous enzyme assay with an automatic phosphate analyzer. The inhibition was shown to be the result of tight binding of fluoride by two catalytically active enzyme-substrate complexes. The reaction between pyrophosphatase and fluoride is relatively slow, so that the rate constants for the binding and release of the inhibitor were derived from phosphate formation curves measured on the time scale of enzyme assays. The pH-dependence of the inhibition reaction in the alkaline medium indicates that both the fluoride-enzyme interaction and the catalytic step of the pyrophosphatase reaction are controlled by the same group on the protein. In the acidic medium, the inhibition is considerably enhanced, presumably because of the protonation of another enzyme group."}
{"id": "PMID:5151", "title": "Hydrolysis of neutral glycerides by lipases of rat brain microsomes.", "content": "The hydrolysis of monoacylglycerol and diacylglycerol by rat brain microsomes was followed by measuring the release of glycerol and monooleylglycerol from dispersions of water insoluble glyceryl esters of oleic acid. The microsomes showed three lipolytic activities. One activity, optimal at pH 4.8, catalyzed the hydrolysis of diacylglycerol but not monoacylglycerol. Two other lipolytic activities, optimal at pH 8.0-8.6, catalyzed the hydrolysis of both diacylglycerol and monoacylglycerol. The pH 8.0-8.6 activities were sensitive to heat and SH-reagents. Detergents were inhibitory in all cases. Extraction of the microsomes with KCl, KSCN, urea or Triton X-100 did not change the ratio of diacylglycerol hydrolysis at pH 4.8 and 8.0. The results of subcellular fractionation studies showed that there was no significant enrichment of the acid lipase in any fraction.", "contents": "Hydrolysis of neutral glycerides by lipases of rat brain microsomes. The hydrolysis of monoacylglycerol and diacylglycerol by rat brain microsomes was followed by measuring the release of glycerol and monooleylglycerol from dispersions of water insoluble glyceryl esters of oleic acid. The microsomes showed three lipolytic activities. One activity, optimal at pH 4.8, catalyzed the hydrolysis of diacylglycerol but not monoacylglycerol. Two other lipolytic activities, optimal at pH 8.0-8.6, catalyzed the hydrolysis of both diacylglycerol and monoacylglycerol. The pH 8.0-8.6 activities were sensitive to heat and SH-reagents. Detergents were inhibitory in all cases. Extraction of the microsomes with KCl, KSCN, urea or Triton X-100 did not change the ratio of diacylglycerol hydrolysis at pH 4.8 and 8.0. The results of subcellular fractionation studies showed that there was no significant enrichment of the acid lipase in any fraction."}
{"id": "PMID:5153", "title": "The effect of soluble rat liver proteins on the activity of microsomal stearoyl-CoA and linoleoyl-CoA desaturase.", "content": "1. The influence of bovine serum albumin and soluble rat liver proteins on the activity of rat liver microsomal delta9 and delta6 desaturases has been studied. 2. In the absence of bovine serum albumin, the delta9 desaturase which converts stearoyl-CoA into oleoyl-CoA, shows a non-linear correlation between enzyme activity and protein concentration. 3. Optimum concentrations of bovine serum albumin have three main effects on the enzyme activity: (i) establishes a linear relationship between enzyme activity and protein concentration, (ii) stimulates the enzyme activity 2--3-fold and (iii) raises the optimum substrate concentration from 10 to 100 muM. 4. A highly purified soluble liver protein of molecular weight 24 000 also stimulated the enzyme activity and brought about a linear relationship between enzyme activity and protein concentration. 5. It was concluded that the non-linear kinetics were due to limiting amounts of substrate binding protein in the microsomal preparations. 6. The delta6 desaturase which converts linoleoyl-CoA into gamma-linolenoyl-CoA was also stimulated by bovine serum albumin and soluble liver proteins. 7. The significance of the fatty acid-binding proteins is discussed.", "contents": "The effect of soluble rat liver proteins on the activity of microsomal stearoyl-CoA and linoleoyl-CoA desaturase. 1. The influence of bovine serum albumin and soluble rat liver proteins on the activity of rat liver microsomal delta9 and delta6 desaturases has been studied. 2. In the absence of bovine serum albumin, the delta9 desaturase which converts stearoyl-CoA into oleoyl-CoA, shows a non-linear correlation between enzyme activity and protein concentration. 3. Optimum concentrations of bovine serum albumin have three main effects on the enzyme activity: (i) establishes a linear relationship between enzyme activity and protein concentration, (ii) stimulates the enzyme activity 2--3-fold and (iii) raises the optimum substrate concentration from 10 to 100 muM. 4. A highly purified soluble liver protein of molecular weight 24 000 also stimulated the enzyme activity and brought about a linear relationship between enzyme activity and protein concentration. 5. It was concluded that the non-linear kinetics were due to limiting amounts of substrate binding protein in the microsomal preparations. 6. The delta6 desaturase which converts linoleoyl-CoA into gamma-linolenoyl-CoA was also stimulated by bovine serum albumin and soluble liver proteins. 7. The significance of the fatty acid-binding proteins is discussed."}
{"id": "PMID:5154", "title": "Control of the formation of extracellular ribonuclease in Neurospora crassa.", "content": "A finding was made that a species of ribonuclease is released into mycelial culture media when a wild-type strain of Neurospora crassa was grown on limiting amounts of phosphate. The ribonuclease activity in the fully derepressed state extends to about 60 to 100 fold of that in the repressed state. The synthesis of the ribonuclease was inhibited by the addition of rifampicin, cycloheximide or orthophosphate. Three molecular species of the ribonuclease were found. Two enzyme fractions showing larger molecular weights were suspected to be aggregates containing the enzyme showing the smallest molecular weight (molecular weight of 10 300). All three fractions showed pH optima of around 7, preferential hydrolysis of polyguanylic acid and poor hydrolysis of guanosine 2',3',-cyclic monophosphate. These characteristics were the same as those of ribonuclease N1, and it was suggested that ribonuclease N1 is a repressible extracellular enzyme. Mutations in the genes nuc-1 and nuc-2 caused loss of ability to derepress this enzyme, but heterokaryon between them partially restored the ability. The nuc-1 mutation was epistatic to the nuc-2 alleles which are partly constitutive in the ribonuclease production.", "contents": "Control of the formation of extracellular ribonuclease in Neurospora crassa. A finding was made that a species of ribonuclease is released into mycelial culture media when a wild-type strain of Neurospora crassa was grown on limiting amounts of phosphate. The ribonuclease activity in the fully derepressed state extends to about 60 to 100 fold of that in the repressed state. The synthesis of the ribonuclease was inhibited by the addition of rifampicin, cycloheximide or orthophosphate. Three molecular species of the ribonuclease were found. Two enzyme fractions showing larger molecular weights were suspected to be aggregates containing the enzyme showing the smallest molecular weight (molecular weight of 10 300). All three fractions showed pH optima of around 7, preferential hydrolysis of polyguanylic acid and poor hydrolysis of guanosine 2',3',-cyclic monophosphate. These characteristics were the same as those of ribonuclease N1, and it was suggested that ribonuclease N1 is a repressible extracellular enzyme. Mutations in the genes nuc-1 and nuc-2 caused loss of ability to derepress this enzyme, but heterokaryon between them partially restored the ability. The nuc-1 mutation was epistatic to the nuc-2 alleles which are partly constitutive in the ribonuclease production."}
{"id": "PMID:5156", "title": "Magnetic and spectroscopic probes for FeOFe linkages in hemin systems.", "content": "Magnetic and spectroscopic properties of mu-oxo-bis-hemins from natural and structurally related porphyrins were investigated as probes for ascertaining the presence or absence of FeIII-O-FeIII linkages between hemin moieties of hemeproteins. Magnetic susceptibilities of solids from 2.2 to 293 degrees K were investigated. The data fit the temperature variations expected for a pair of antiferromagnetically coupled S = 5/2, iron (III) porphyrins with J values of 175, 190, 195, 205, and 210 degrees K for deuterohemins with hydrogen, vinyl, 2'-ethoxycarbonylcyclopropyl, acetyl, propionyl, and ethyl 2,4-substituents, respectively. This magnetic character is reflected in PMR spectra that exhibit resonances with far less broadening and paramagnetic shift than is the case for monomeric high-spin hemins. Only impurities are seen in EPR spectra, which serve effectively in monitoring the magnetic purity of preparations. An infrared active asymmetric stretching frequency characteristic of the FeOFe linkage can be identified by substitution of 160 by 180. Electronic spectra are highly characteristic with poorly resolved absorption bands. The substituents on the porphyrin ring exert significant, but usually not large, electronic and steric effects on these properties. Solvent effects were relatively small and no firm evidence for binding of ligands trans to bridging oxygen was found. The uniqueness of these physical properties and their low sensitivity to changes in porphyrin structure or medium facilitates the identification of mu-oxo linkage in hemins or oxidized hemeproteins.", "contents": "Magnetic and spectroscopic probes for FeOFe linkages in hemin systems. Magnetic and spectroscopic properties of mu-oxo-bis-hemins from natural and structurally related porphyrins were investigated as probes for ascertaining the presence or absence of FeIII-O-FeIII linkages between hemin moieties of hemeproteins. Magnetic susceptibilities of solids from 2.2 to 293 degrees K were investigated. The data fit the temperature variations expected for a pair of antiferromagnetically coupled S = 5/2, iron (III) porphyrins with J values of 175, 190, 195, 205, and 210 degrees K for deuterohemins with hydrogen, vinyl, 2'-ethoxycarbonylcyclopropyl, acetyl, propionyl, and ethyl 2,4-substituents, respectively. This magnetic character is reflected in PMR spectra that exhibit resonances with far less broadening and paramagnetic shift than is the case for monomeric high-spin hemins. Only impurities are seen in EPR spectra, which serve effectively in monitoring the magnetic purity of preparations. An infrared active asymmetric stretching frequency characteristic of the FeOFe linkage can be identified by substitution of 160 by 180. Electronic spectra are highly characteristic with poorly resolved absorption bands. The substituents on the porphyrin ring exert significant, but usually not large, electronic and steric effects on these properties. Solvent effects were relatively small and no firm evidence for binding of ligands trans to bridging oxygen was found. The uniqueness of these physical properties and their low sensitivity to changes in porphyrin structure or medium facilitates the identification of mu-oxo linkage in hemins or oxidized hemeproteins."}
{"id": "PMID:5157", "title": "Copper (II) induced polymerization of human albumin, and its depolymerization by diglycyl-L-histidine: a pH static and ultracentrifugation study.", "content": "Copper (II) ions successively induce dimers and tetramers of human serum albumin (L) when the Cu (II) concentration is extended beyond that of 200 muM. This is shown by emf titrations and by ultracentrifugation experiments. The emf titrations, which involve a new pH static method, were performed at 25 degrees, in a 0.5 M NaCIO4 medium at pH 6.59, using glass and copper amalgam electrodes. The total concentration of Cu(II) varied from 0.14 to 2.2 mM and the albumin concentration from 0.05 to 0.7 mM. In order to evaluate the formula of the main complexes, without using any a priori assumptions regarding their compositions, a detailed graphic procedure was used. The results, in the form of equilibrium constants for the main species, were refined by the use of a general least squares computer program. The experimental data are found to be consistent with the formation of the monomeric CuL, Cu5L, and Cu6L species and the dimeric Cu3L2, Cu4L, Cu6L, and Cu8L2 species. In addition, there is some indication for a minor species, most probably the Cu12L4 tetramer. The pH static results qualitatively agree with the findings obtained by ultracentrifugation. As indicated by distinct bands and their S-values, ultracentrifugation experiments show not only monomeric and dimeric species of albumin, but also tetrameric species. The polymerization of the albumin is reversible, since diglycyl-L-histidine, a peptide designed to mimic the Cu (II) transport site of albumin, depolymerizes the Cu (II)-albumin polymers.", "contents": "Copper (II) induced polymerization of human albumin, and its depolymerization by diglycyl-L-histidine: a pH static and ultracentrifugation study. Copper (II) ions successively induce dimers and tetramers of human serum albumin (L) when the Cu (II) concentration is extended beyond that of 200 muM. This is shown by emf titrations and by ultracentrifugation experiments. The emf titrations, which involve a new pH static method, were performed at 25 degrees, in a 0.5 M NaCIO4 medium at pH 6.59, using glass and copper amalgam electrodes. The total concentration of Cu(II) varied from 0.14 to 2.2 mM and the albumin concentration from 0.05 to 0.7 mM. In order to evaluate the formula of the main complexes, without using any a priori assumptions regarding their compositions, a detailed graphic procedure was used. The results, in the form of equilibrium constants for the main species, were refined by the use of a general least squares computer program. The experimental data are found to be consistent with the formation of the monomeric CuL, Cu5L, and Cu6L species and the dimeric Cu3L2, Cu4L, Cu6L, and Cu8L2 species. In addition, there is some indication for a minor species, most probably the Cu12L4 tetramer. The pH static results qualitatively agree with the findings obtained by ultracentrifugation. As indicated by distinct bands and their S-values, ultracentrifugation experiments show not only monomeric and dimeric species of albumin, but also tetrameric species. The polymerization of the albumin is reversible, since diglycyl-L-histidine, a peptide designed to mimic the Cu (II) transport site of albumin, depolymerizes the Cu (II)-albumin polymers."}
{"id": "PMID:5158", "title": "Studies on Copper-Acetylglycylglycine System.", "content": "Reported here are studies on the copper-acetylgylcylglycine system as a function of pH and the molar ratio between the ligand and the paramagnetic ion, applying potentiometric titration, magnetic resonances (esr and nmr) and spectrophotometric techniques. The results indicate that depending on the pH of the solutions there are three distinct regions characterized by their different species and behavior. In region I (pH less than 6.5), the copper is bound to the carboxylate group of the ligand molecule (the \"blue\" complex). Precipitation of copper occurs in region II (pH-7). In region III (pH greater than 9), in the presence of excess of ligand, the copper redissolves, forming complexes in which the central copper ion binds to the peptide molecule, through the nitrogens of the deprotonated peptide groups, and to hydroxyl ions. The mutual replacement of the peptide groups of chelated AcGlyGly by OH- and the changes in the structures of the complexes are discussed.", "contents": "Studies on Copper-Acetylglycylglycine System. Reported here are studies on the copper-acetylgylcylglycine system as a function of pH and the molar ratio between the ligand and the paramagnetic ion, applying potentiometric titration, magnetic resonances (esr and nmr) and spectrophotometric techniques. The results indicate that depending on the pH of the solutions there are three distinct regions characterized by their different species and behavior. In region I (pH less than 6.5), the copper is bound to the carboxylate group of the ligand molecule (the \"blue\" complex). Precipitation of copper occurs in region II (pH-7). In region III (pH greater than 9), in the presence of excess of ligand, the copper redissolves, forming complexes in which the central copper ion binds to the peptide molecule, through the nitrogens of the deprotonated peptide groups, and to hydroxyl ions. The mutual replacement of the peptide groups of chelated AcGlyGly by OH- and the changes in the structures of the complexes are discussed."}
{"id": "PMID:5155", "title": "[Effect of pH on the separation of rat liver cells].", "content": "The effect of calcium ions, temperature and pH on the number of cells separated in the course of dispersion procedure was studied. The maximum number of separated cells corresponds to pH 6.8. Mechanical resistibility of the cells in suspension was found to grow linearly within pH interval 5.2-8.8.", "contents": "[Effect of pH on the separation of rat liver cells]. The effect of calcium ions, temperature and pH on the number of cells separated in the course of dispersion procedure was studied. The maximum number of separated cells corresponds to pH 6.8. Mechanical resistibility of the cells in suspension was found to grow linearly within pH interval 5.2-8.8."}
{"id": "PMID:5162", "title": "A method for the estimation of acetanilide, paracetamol and phenacetin in plasma and urine using mass fragmentography.", "content": "Phenacetin, paracetamol and acetanilide can be determined in a plasma or urine sample by the use of deuterium labelled analogues. These are produced by reaction of hexadeuterioacetic anhydride with the appropriate aromatic amine. The -NHCOCD3 group is stable to hydrogen exchange below pH 8. The internal standard is added to the plasma or urine after enzymatic hydrolysis of the paracetamol conjugates and an ethyl acetate extract at pH 5 is evaporated under nitrogen and the residue derivatized with N,O-bis-(trimethylsilyl)-acetamide. An aliquot of this solution is injected into a g.c.m.s. system, and one ion characteristic of the material under study and the ion from the deuterium analogue (3 mass units greater) are monitored using a voltage switching technique. In the case of phenacetin, for example, ions at 251 and 254 are monitored. Calibration curves relating different weight ratios of the hydrogen and deuterium compounds to their respective signals from the gas chromatography mass spectrometer are used to calculate the amount of a compound in a particular sample. These methods have been developed to study the oxidation of acetanilide to paracetamol and the de-ethylation of phenacetin to paracetamol. Preliminary results from experiments with phenacetin will be discussed.", "contents": "A method for the estimation of acetanilide, paracetamol and phenacetin in plasma and urine using mass fragmentography. Phenacetin, paracetamol and acetanilide can be determined in a plasma or urine sample by the use of deuterium labelled analogues. These are produced by reaction of hexadeuterioacetic anhydride with the appropriate aromatic amine. The -NHCOCD3 group is stable to hydrogen exchange below pH 8. The internal standard is added to the plasma or urine after enzymatic hydrolysis of the paracetamol conjugates and an ethyl acetate extract at pH 5 is evaporated under nitrogen and the residue derivatized with N,O-bis-(trimethylsilyl)-acetamide. An aliquot of this solution is injected into a g.c.m.s. system, and one ion characteristic of the material under study and the ion from the deuterium analogue (3 mass units greater) are monitored using a voltage switching technique. In the case of phenacetin, for example, ions at 251 and 254 are monitored. Calibration curves relating different weight ratios of the hydrogen and deuterium compounds to their respective signals from the gas chromatography mass spectrometer are used to calculate the amount of a compound in a particular sample. These methods have been developed to study the oxidation of acetanilide to paracetamol and the de-ethylation of phenacetin to paracetamol. Preliminary results from experiments with phenacetin will be discussed."}
{"id": "PMID:5168", "title": "Studies on the chemical nature of urinary chemiluminescence.", "content": "Studies on the nature of the chemicals responsible for urinary chemiluminescence have been carried out. Urinary chemiluminescence can be increased slightly by sulphatase, more by glucuronidase but most of all by boiling for 1 hour at pH 1. It is suggested that most of the chemicals responsible for urinary chemiluminescence are bound as non-chemiluminescent precursors to sulphate, glucuronic acid and in other ways. Both the chemiluminescent material and the inactive precursors are freely ultrafiltrable with molecular weights below 500. A survey of various chemicals has revealed considerable chemiluminescence in certain metabolites of naphthylamines and known to cause bladder cancer but little or no chemoluminescence in the tryptophane metabolites that have been thought to cause bladder cancer.", "contents": "Studies on the chemical nature of urinary chemiluminescence. Studies on the nature of the chemicals responsible for urinary chemiluminescence have been carried out. Urinary chemiluminescence can be increased slightly by sulphatase, more by glucuronidase but most of all by boiling for 1 hour at pH 1. It is suggested that most of the chemicals responsible for urinary chemiluminescence are bound as non-chemiluminescent precursors to sulphate, glucuronic acid and in other ways. Both the chemiluminescent material and the inactive precursors are freely ultrafiltrable with molecular weights below 500. A survey of various chemicals has revealed considerable chemiluminescence in certain metabolites of naphthylamines and known to cause bladder cancer but little or no chemoluminescence in the tryptophane metabolites that have been thought to cause bladder cancer."}
{"id": "PMID:5174", "title": "Role of the practitioner, public health officer, dermatologist, and other specialists in the teaching, investigation and treatment of STD. The situation in the Common Market countries.", "content": "The training of undergraduates and postgraduates in the original member countries of the European Community (Belgium, Federal Republic of Germany, France, Italy, Luxemburg, and the Netherlands) is outlined and compared with training in the U.K. and Ireland. It is noted that, in the European Community, training is inadequate and should be improved. Harmonizing with the U.K. will require concessions to be made on both sides.", "contents": "Role of the practitioner, public health officer, dermatologist, and other specialists in the teaching, investigation and treatment of STD. The situation in the Common Market countries. The training of undergraduates and postgraduates in the original member countries of the European Community (Belgium, Federal Republic of Germany, France, Italy, Luxemburg, and the Netherlands) is outlined and compared with training in the U.K. and Ireland. It is noted that, in the European Community, training is inadequate and should be improved. Harmonizing with the U.K. will require concessions to be made on both sides."}
{"id": "PMID:5175", "title": "Effects of axotomy on the trans-synaptic regulation of enzyme activity in adult rat superior cervical ganglia.", "content": "The effects of surgical transection of the postganglionic nerve trunk of the superior cervical ganglion on the total protein content and levels of the enzymes tyrosine hydroxylase, DOPA decarboxylase and choline acetyltransferase have been studied in the adult rat. There is a minor decrease in the total activities of these 3 enzymes accompanied by a large increase in the total protein content of the ganglion. The trans-synaptic induction of the enzyme tyrosine hydroxylase by reserpine is not affected by postganglionic axotomy. Increased activity mediated by reserpine caused no change in the total activities of either DOPA decarboxylase or choline acetyltransferase. Previously observed effects of postganglionic axotomy on preventing transmission through the ganglion are compared with these results and the possible mechanisms by which trans-synaptic induction may occur are discussed.", "contents": "Effects of axotomy on the trans-synaptic regulation of enzyme activity in adult rat superior cervical ganglia. The effects of surgical transection of the postganglionic nerve trunk of the superior cervical ganglion on the total protein content and levels of the enzymes tyrosine hydroxylase, DOPA decarboxylase and choline acetyltransferase have been studied in the adult rat. There is a minor decrease in the total activities of these 3 enzymes accompanied by a large increase in the total protein content of the ganglion. The trans-synaptic induction of the enzyme tyrosine hydroxylase by reserpine is not affected by postganglionic axotomy. Increased activity mediated by reserpine caused no change in the total activities of either DOPA decarboxylase or choline acetyltransferase. Previously observed effects of postganglionic axotomy on preventing transmission through the ganglion are compared with these results and the possible mechanisms by which trans-synaptic induction may occur are discussed."}
{"id": "PMID:5176", "title": "The effects of putative neurotransmitters on the resting membrane potential of dissociated brain neurones in culture.", "content": "Cultures established from mechanically dissociated neonatal mouse brains were found to be suitable for electrophysiological investigation of drug action. During culture most cells were aggregated into either monolayer regions or thick cords joining monolayer regions. A few cells remained isolated. The neurones in the monolayer regions were distinguished from glial cells by differential staining, and were found to be the best subject for intracellular recording. Frequency of resting membrane potentials of these cells proved to be reproducible in cultures of the same age, and were a useful index of sensitivity to bath applied drugs. Acetylcholine, dopamine, histamine, serotonin and noradrenaline depolarized various neurones; GABA caused hyperpolarization, while glutamate and glycine had no significant effect. Antagonism of the responses to acetylcholine, dopamine, serotonin and GABA was seen using atropine, pimozide, methysergide and bicuculline respectively. It is concluded that dissociated brain neurones in culture show chemosensitivity and may be useful in further pharmacological studies.", "contents": "The effects of putative neurotransmitters on the resting membrane potential of dissociated brain neurones in culture. Cultures established from mechanically dissociated neonatal mouse brains were found to be suitable for electrophysiological investigation of drug action. During culture most cells were aggregated into either monolayer regions or thick cords joining monolayer regions. A few cells remained isolated. The neurones in the monolayer regions were distinguished from glial cells by differential staining, and were found to be the best subject for intracellular recording. Frequency of resting membrane potentials of these cells proved to be reproducible in cultures of the same age, and were a useful index of sensitivity to bath applied drugs. Acetylcholine, dopamine, histamine, serotonin and noradrenaline depolarized various neurones; GABA caused hyperpolarization, while glutamate and glycine had no significant effect. Antagonism of the responses to acetylcholine, dopamine, serotonin and GABA was seen using atropine, pimozide, methysergide and bicuculline respectively. It is concluded that dissociated brain neurones in culture show chemosensitivity and may be useful in further pharmacological studies."}
{"id": "PMID:5178", "title": "A quantitative comparison of the formation of synapses in the rat superior cervical sympathetic ganglion by its own and by foreign nerve fibres.", "content": "The rat superior cervical sympathetic ganglion (SCG) has about 36,000 neurones in a volume of about 1 cu.mm. There are about 8.8 X 10(6) synapses, and 6000-9000 preganglionic axons. Section of the preganglionic chain causes a loss of 93% of the synapses. In the denervated SCG there are 0.6 X 10(6) remaining ('intrinsic') synapses, and a proportion of the synaptic sites are identifiable as vacated synaptic thickenings (3 X 10(6) per SCG, as compared with 0.5 X 10(6) in the normal intact SCG). After deducting the intrinsic synapses, this indicates that each preganglionic axon forms about 1100 (900-1400) synapses. After freezing the preganglionic chain, subsequent axonal regeneration restores synapse numbers to 85% of normal (7.5 X 10(6) synapses per SCG). After anastomotic repair by suture of the cut ends of the preganglionic chain (a necessary control for the foreign nerve anastomoses), the SCG contains only 60% of the normal complement of synapses (5.2 X 10(6) synapses per SCG). The results of this anastomosis are very variable. However, in individual ganglia the numbers of synapses are directly correlated with the numbers of axons which reach the SCG. After deducting the intrinsic synapses it can be calculated that each axon forms about 700 synapses. This is probably an underestimation of the numbers which would be achieved at longer survival times. After anastomosis of the vagal nerve into the denervated SCG there are about 4.4 X 10(6) synapses per SCG. Morphologically the majority have axon terminals with large dense cored vesicles, and it is likely that these belong to the axons of the parasympathetic preganglionic neurones in the dorsal motor nucleus of the vagus. A smaller population of axon terminals are devoid of large dense cored vesicles; their origin is unknown. The dorsal motor nucleus of the vagus has between 1000 and 2000 neurones. After deducting the intrinsic synapses, this indicates that each axon may form up to 1900-3800 synapses. To the extent that other, unidentified vagal fibres also contribute to the synapses found after this anastomosis, this figure is an overestimate. After anastomosis of the hypoglossal nerve into the denervated SCG, there are 1.5 X 10(6) synapses per SCG. A morphologically distinctive type of axon terminal is found, and it is argued that this may belong to a special category of skeletomotor neurones located in the caudoventral part of the hypoglossal nucleus and distinguished by pseudocholinesterase staining. There are about 600 of these neurones, which would indicate that they form about 1500 synapses per axon (after deducting the numbers of intrinsic synapses). The majority of the hypoglossal neurones do not form intraganglionic synapses; this suggests that although the possession of a cholinergic mechanism may be necessary for axons to be able to form ganglionic synapses, it is not in itself sufficient. For each of the types of anastomosis, the numbers of vacated thickenings are inversely proportional to the numbers of synapses...", "contents": "A quantitative comparison of the formation of synapses in the rat superior cervical sympathetic ganglion by its own and by foreign nerve fibres. The rat superior cervical sympathetic ganglion (SCG) has about 36,000 neurones in a volume of about 1 cu.mm. There are about 8.8 X 10(6) synapses, and 6000-9000 preganglionic axons. Section of the preganglionic chain causes a loss of 93% of the synapses. In the denervated SCG there are 0.6 X 10(6) remaining ('intrinsic') synapses, and a proportion of the synaptic sites are identifiable as vacated synaptic thickenings (3 X 10(6) per SCG, as compared with 0.5 X 10(6) in the normal intact SCG). After deducting the intrinsic synapses, this indicates that each preganglionic axon forms about 1100 (900-1400) synapses. After freezing the preganglionic chain, subsequent axonal regeneration restores synapse numbers to 85% of normal (7.5 X 10(6) synapses per SCG). After anastomotic repair by suture of the cut ends of the preganglionic chain (a necessary control for the foreign nerve anastomoses), the SCG contains only 60% of the normal complement of synapses (5.2 X 10(6) synapses per SCG). The results of this anastomosis are very variable. However, in individual ganglia the numbers of synapses are directly correlated with the numbers of axons which reach the SCG. After deducting the intrinsic synapses it can be calculated that each axon forms about 700 synapses. This is probably an underestimation of the numbers which would be achieved at longer survival times. After anastomosis of the vagal nerve into the denervated SCG there are about 4.4 X 10(6) synapses per SCG. Morphologically the majority have axon terminals with large dense cored vesicles, and it is likely that these belong to the axons of the parasympathetic preganglionic neurones in the dorsal motor nucleus of the vagus. A smaller population of axon terminals are devoid of large dense cored vesicles; their origin is unknown. The dorsal motor nucleus of the vagus has between 1000 and 2000 neurones. After deducting the intrinsic synapses, this indicates that each axon may form up to 1900-3800 synapses. To the extent that other, unidentified vagal fibres also contribute to the synapses found after this anastomosis, this figure is an overestimate. After anastomosis of the hypoglossal nerve into the denervated SCG, there are 1.5 X 10(6) synapses per SCG. A morphologically distinctive type of axon terminal is found, and it is argued that this may belong to a special category of skeletomotor neurones located in the caudoventral part of the hypoglossal nucleus and distinguished by pseudocholinesterase staining. There are about 600 of these neurones, which would indicate that they form about 1500 synapses per axon (after deducting the numbers of intrinsic synapses). The majority of the hypoglossal neurones do not form intraganglionic synapses; this suggests that although the possession of a cholinergic mechanism may be necessary for axons to be able to form ganglionic synapses, it is not in itself sufficient. For each of the types of anastomosis, the numbers of vacated thickenings are inversely proportional to the numbers of synapses..."}
{"id": "PMID:5179", "title": "Properties of soluble and particulate cysteine sulfinate decarboxylase of the adult and the developing rat brain.", "content": "Some properties of cysteine sulfinate decarboxylase (CSD) activity were studied in the pellet and supernatant of a 18,000 X g centrifugation of isotonic sucrose rat brain homogenates. About 50% of the enzyme activity was found associated to the particulate fraction and 16% of the activity remained particle bound after hypo-osmotic shock of the 18,000 X g pellet. The activity of the 18,000 X g supernatant showed a lower dependence on exogenous pyridoxal phosphate (PLP) than the activity in the particulate fraction. The CSD activity of these fractions also differed in optimal pH and in apparent kinetic constants. The enzyme associated to particles showed the highest Vmax and the lowest Km. The activity and kinetic characteristics of CSD were studied during brain postnatal development. In the newborn brain only a small amount of the enzyme activity was found associated to the 18,000 X g pellet. CSD in brain homogenates of immature rats was less dependent on free PLP and showed a higher Km and a lower Vmax as compared with the enzyme in the adult brain. Between birth and adulthood the enzyme activity increased more than 10-fold in the particulate fraction and 2-fold in the soluble fraction. It is concluded that the differences observed in CSD activity between newborn and adult brain are due to an increase of the particulate form of the enzyme during postnatal development.", "contents": "Properties of soluble and particulate cysteine sulfinate decarboxylase of the adult and the developing rat brain. Some properties of cysteine sulfinate decarboxylase (CSD) activity were studied in the pellet and supernatant of a 18,000 X g centrifugation of isotonic sucrose rat brain homogenates. About 50% of the enzyme activity was found associated to the particulate fraction and 16% of the activity remained particle bound after hypo-osmotic shock of the 18,000 X g pellet. The activity of the 18,000 X g supernatant showed a lower dependence on exogenous pyridoxal phosphate (PLP) than the activity in the particulate fraction. The CSD activity of these fractions also differed in optimal pH and in apparent kinetic constants. The enzyme associated to particles showed the highest Vmax and the lowest Km. The activity and kinetic characteristics of CSD were studied during brain postnatal development. In the newborn brain only a small amount of the enzyme activity was found associated to the 18,000 X g pellet. CSD in brain homogenates of immature rats was less dependent on free PLP and showed a higher Km and a lower Vmax as compared with the enzyme in the adult brain. Between birth and adulthood the enzyme activity increased more than 10-fold in the particulate fraction and 2-fold in the soluble fraction. It is concluded that the differences observed in CSD activity between newborn and adult brain are due to an increase of the particulate form of the enzyme during postnatal development."}
{"id": "PMID:5180", "title": "[Tissue lactates, pH and blood gasses in hibernating dormouse: changes during periodic arousals].", "content": "Periodic arousal in the garden dormouse is accompagnied by a rise in plasma and muscle lactate levels and a diminution of muscle glycogen. In addition, the decrease of arterial blood pH and O2 concentration agrees well with these results. All of which are in good agreement with the general stimulation of adrenergic activity observed at the onset of rewarming.", "contents": "[Tissue lactates, pH and blood gasses in hibernating dormouse: changes during periodic arousals]. Periodic arousal in the garden dormouse is accompagnied by a rise in plasma and muscle lactate levels and a diminution of muscle glycogen. In addition, the decrease of arterial blood pH and O2 concentration agrees well with these results. All of which are in good agreement with the general stimulation of adrenergic activity observed at the onset of rewarming."}
{"id": "PMID:5181", "title": "Study of the natural antihistamine-like substance in bile in mammals.", "content": "A natural antihistamine substance (NAS) present in bile has been investigated. It was found that the antihistamine activity was not due to proteins, lipids, pigments, or amino acids. On ion exchange chromatography and thin-layer chromatography, this activity was associated with bile acids. Many bile acids could, in varying degrees, inhibit this histamine induced guinea pig ileum contraction, desoxycholic acid being the most potent. However NAS activity could be separated from bile acids and their conjugates using a different solvent system. Furthermore, NAS showed a higher antihistamine activity than bile acids. This substance seems to be responsible for 15-20% of the activity of whole bile. The substance has not yet been identified.", "contents": "Study of the natural antihistamine-like substance in bile in mammals. A natural antihistamine substance (NAS) present in bile has been investigated. It was found that the antihistamine activity was not due to proteins, lipids, pigments, or amino acids. On ion exchange chromatography and thin-layer chromatography, this activity was associated with bile acids. Many bile acids could, in varying degrees, inhibit this histamine induced guinea pig ileum contraction, desoxycholic acid being the most potent. However NAS activity could be separated from bile acids and their conjugates using a different solvent system. Furthermore, NAS showed a higher antihistamine activity than bile acids. This substance seems to be responsible for 15-20% of the activity of whole bile. The substance has not yet been identified."}
{"id": "PMID:5182", "title": "Spin labels as probes for tetraphenylboron ion interaction with liposomes.", "content": "The effects of tetraphenylboron (TFB) on the molecular organization of lipids within phosphatidylcholine (PC) liposomes were investigated using the spin-labeled method. Perturbations at the surface of the lipid were probed using stearamide and cholestane spin labels; perturbations in the hydrophobic-portion were probed with spin-labeled amphiphilic fatty esters.", "contents": "Spin labels as probes for tetraphenylboron ion interaction with liposomes. The effects of tetraphenylboron (TFB) on the molecular organization of lipids within phosphatidylcholine (PC) liposomes were investigated using the spin-labeled method. Perturbations at the surface of the lipid were probed using stearamide and cholestane spin labels; perturbations in the hydrophobic-portion were probed with spin-labeled amphiphilic fatty esters."}
{"id": "PMID:5183", "title": "The subcellular distribution and properties of Crithidia sp. hydrolases with particular reference to pyrophosphate and orthophosphate monoester phosphohydrolases.", "content": "A cell fractionation scheme was developed for studying the distribution of certain hydrolases, especially phosphohydrolases in a Crithidia sp. (Trypanosomatidae). Whilst between 26-56% of the total cellular hydrolase activities were soluble (probably of flagellar pocket origin), a certain percentage, 5-40%, was sedimentable. A particulate fraction obtained after isopycnic density gradient centrifugation (p = 1.187-1.241), designated fraction FA/FB, was enriched in various acid hydrolases (relative specific activities 1.33-6.24) and displayed latent phosphohydrolase activities. The density gradient distributions of this hydrolytic enzymes were compared with reference to one another and malate dehydrogenase (mitochondrial marker). From the results obtained it appears that the sedimentable acid hydrolases of Crithidia are associated with a heterogeneous population of subcellular particles. Cytochemical observations on the FA/FB fraction supported this finding and revealed the association of acid phosphatase reaction product with subcellular elements resembling multivesicular bodies.", "contents": "The subcellular distribution and properties of Crithidia sp. hydrolases with particular reference to pyrophosphate and orthophosphate monoester phosphohydrolases. A cell fractionation scheme was developed for studying the distribution of certain hydrolases, especially phosphohydrolases in a Crithidia sp. (Trypanosomatidae). Whilst between 26-56% of the total cellular hydrolase activities were soluble (probably of flagellar pocket origin), a certain percentage, 5-40%, was sedimentable. A particulate fraction obtained after isopycnic density gradient centrifugation (p = 1.187-1.241), designated fraction FA/FB, was enriched in various acid hydrolases (relative specific activities 1.33-6.24) and displayed latent phosphohydrolase activities. The density gradient distributions of this hydrolytic enzymes were compared with reference to one another and malate dehydrogenase (mitochondrial marker). From the results obtained it appears that the sedimentable acid hydrolases of Crithidia are associated with a heterogeneous population of subcellular particles. Cytochemical observations on the FA/FB fraction supported this finding and revealed the association of acid phosphatase reaction product with subcellular elements resembling multivesicular bodies."}
{"id": "PMID:5184", "title": "Acid proteases from species of Mucor. IV. Hydrogen-tritium exchange of Mucor miehei protease.", "content": "The kinetics of hydrogen-tritium exchange were studied in the range pH-3 for both the fully and partially tritiated protein. Exchange constants for an intermediate class and slow class of hydrogens were determined and found to give a parabolic curve characteristic of acid and base catalysis about the observed pHmin of 4.03. The anomalous rate retardation on the acid portion of the curve was attributed to electrostatic interactions which could be evaluated quantitatively from the titration data. Partial tritation and pH cross-over experiments indicated that the rank order was pH-independent thus eliminating the possiblitity of a major conformational change. Consequently, the data are most likely explicable in terms of restricted solvent accessibility.", "contents": "Acid proteases from species of Mucor. IV. Hydrogen-tritium exchange of Mucor miehei protease. The kinetics of hydrogen-tritium exchange were studied in the range pH-3 for both the fully and partially tritiated protein. Exchange constants for an intermediate class and slow class of hydrogens were determined and found to give a parabolic curve characteristic of acid and base catalysis about the observed pHmin of 4.03. The anomalous rate retardation on the acid portion of the curve was attributed to electrostatic interactions which could be evaluated quantitatively from the titration data. Partial tritation and pH cross-over experiments indicated that the rank order was pH-independent thus eliminating the possiblitity of a major conformational change. Consequently, the data are most likely explicable in terms of restricted solvent accessibility."}
{"id": "PMID:5185", "title": "Some properties of acetylcholinesterase from rat retina.", "content": "Acetylcholinesterase (AChE, EC 3.1.1.7) of rat retina was studied with respect to its kinetic and other properties, and a comparison was made with the enzyme from brain. The subcellular distribution of the retinal AChE showed that the enzyme was concentrated in the synaptosomal-mitochondrial fraction although in the brain the AChE was distributed more evenly between the fractions studied. The enzyme from both retina and brain was easily solubilised and exhibited a Km of the order of 10(-4) M. The pH optimum was 8.3-8.6 for the AChE from both tissues for both the soluble and particulate enzyme.", "contents": "Some properties of acetylcholinesterase from rat retina. Acetylcholinesterase (AChE, EC 3.1.1.7) of rat retina was studied with respect to its kinetic and other properties, and a comparison was made with the enzyme from brain. The subcellular distribution of the retinal AChE showed that the enzyme was concentrated in the synaptosomal-mitochondrial fraction although in the brain the AChE was distributed more evenly between the fractions studied. The enzyme from both retina and brain was easily solubilised and exhibited a Km of the order of 10(-4) M. The pH optimum was 8.3-8.6 for the AChE from both tissues for both the soluble and particulate enzyme."}
{"id": "PMID:5188", "title": "The metabolic activation of the carcinogen 1'-hydroxysafrole in vivo and in vitro and the electrophilic reactivities of possible ultimate carcinogens.", "content": "Administration of [2',3'-3H]-1'-hydroxysafrole to rats or mice resulted in the formation of hepatic DNA-, ribosomal RNA-, and protein-bound 3H derivatives. Alkaline digestion of the 3H-protein released 0.1 to 0.3% of the 3H as a derivative that was identified as 3'-methylmercaptoisosafrole by its cochromatography in five solvent systems with the synthetic compound. 1'-Hydroxysafrole was metabolized at a low rate by rat and mouse liver cytosols in a 3'-phosphoadenosine 5'-phosphosulfate-dependent reaction to a derivative (presumably the sulfuric acid ester) that was captured by its reaction with RNA. Likewise, 1'-hydroxysafrole was oxidized at a low rate by rat and mouse liver microsomes to 1'-hydroxysafrole-2',3'-oxide in a reduced nicotinamide adenine dinucleotide phosphate-dependent reaction. Both of these electrophilic metabolites are candidate ultimate carcinogenic derivatives of 1'-hydroxysafrole. The electrophilic reactivities of various safrole derivatives with nucleosides were determined to be in the order of 1'-oxosafrole greater than 1'-acetoxysafrole greater than 1'-acetoxysafrole-2',3'-oxide greater than 1'-hydroxysafrole-2',3'-oxide greater than safrole-2',3'-oxide greater than or equal to 1'-oxosafrole-2',3'-oxide. The major reactions were generally observed with guanosine. A major reaction product of 1'-acetoxysafrole and guanosine 5'-monophosphate yielded 3'-hydroxyisosafrole under very mild acidic conditions. These data further substantiate the previous characterization of this reaction product as O-6-(isosafrol-3'-yl)guanylic acid. The syntheses of 1'-oxosafrole, 2',3'-dehydrosafrole, [2',3'-3H]-1'-hydroxysafrole, and the 2',3'-oxed.", "contents": "The metabolic activation of the carcinogen 1'-hydroxysafrole in vivo and in vitro and the electrophilic reactivities of possible ultimate carcinogens. Administration of [2',3'-3H]-1'-hydroxysafrole to rats or mice resulted in the formation of hepatic DNA-, ribosomal RNA-, and protein-bound 3H derivatives. Alkaline digestion of the 3H-protein released 0.1 to 0.3% of the 3H as a derivative that was identified as 3'-methylmercaptoisosafrole by its cochromatography in five solvent systems with the synthetic compound. 1'-Hydroxysafrole was metabolized at a low rate by rat and mouse liver cytosols in a 3'-phosphoadenosine 5'-phosphosulfate-dependent reaction to a derivative (presumably the sulfuric acid ester) that was captured by its reaction with RNA. Likewise, 1'-hydroxysafrole was oxidized at a low rate by rat and mouse liver microsomes to 1'-hydroxysafrole-2',3'-oxide in a reduced nicotinamide adenine dinucleotide phosphate-dependent reaction. Both of these electrophilic metabolites are candidate ultimate carcinogenic derivatives of 1'-hydroxysafrole. The electrophilic reactivities of various safrole derivatives with nucleosides were determined to be in the order of 1'-oxosafrole greater than 1'-acetoxysafrole greater than 1'-acetoxysafrole-2',3'-oxide greater than 1'-hydroxysafrole-2',3'-oxide greater than safrole-2',3'-oxide greater than or equal to 1'-oxosafrole-2',3'-oxide. The major reactions were generally observed with guanosine. A major reaction product of 1'-acetoxysafrole and guanosine 5'-monophosphate yielded 3'-hydroxyisosafrole under very mild acidic conditions. These data further substantiate the previous characterization of this reaction product as O-6-(isosafrol-3'-yl)guanylic acid. The syntheses of 1'-oxosafrole, 2',3'-dehydrosafrole, [2',3'-3H]-1'-hydroxysafrole, and the 2',3'-oxed."}
{"id": "PMID:5189", "title": "Intrinsic resistance to methotrexate of cultured mammalian cells in relation to the inhibition kinetics of their dihydrololate reductases.", "content": "Four cultured mammalian cell lines, differing in intrinsic resistance to methotrexate over a 70-fold range, have been compared with respect to several biochemical factors that might influence response to the drug. Cellular activity of the enzymes dihydrofolate reductase and thymidylate synthetase and the total levels of folate cofactors did not vary by more than a factor of 2 among the cell lines. All the cell types were able to transport extracellular methotrexate efficiently across the cell membrane, and at comparable rates. A kinetic study of highly purified dihydrofolate reductases from the four sources revealed small differences in the Km values for dihydrofolate and reduced nicotinamide adenine dinucleotide phosphate. A study was made of the inhibition of the four dihydrofolate reductases by methotrexate, and Ki values were obtained by fitting the Zone B equation of Goldstein (Goldstein, A., J. Gen. Physiol., 27: 529-580, 1944) to the resulting data. Values Ki determined by this method correlated with intrinsic resistance of the cell lines and showed a 25-fold range from the most sensitive to the most resistant line. It is concluded that the response of a cell to methotrexate is significantly influenced by the dissociation constant of its dihydrofolate reductase-methotrexate complex.", "contents": "Intrinsic resistance to methotrexate of cultured mammalian cells in relation to the inhibition kinetics of their dihydrololate reductases. Four cultured mammalian cell lines, differing in intrinsic resistance to methotrexate over a 70-fold range, have been compared with respect to several biochemical factors that might influence response to the drug. Cellular activity of the enzymes dihydrofolate reductase and thymidylate synthetase and the total levels of folate cofactors did not vary by more than a factor of 2 among the cell lines. All the cell types were able to transport extracellular methotrexate efficiently across the cell membrane, and at comparable rates. A kinetic study of highly purified dihydrofolate reductases from the four sources revealed small differences in the Km values for dihydrofolate and reduced nicotinamide adenine dinucleotide phosphate. A study was made of the inhibition of the four dihydrofolate reductases by methotrexate, and Ki values were obtained by fitting the Zone B equation of Goldstein (Goldstein, A., J. Gen. Physiol., 27: 529-580, 1944) to the resulting data. Values Ki determined by this method correlated with intrinsic resistance of the cell lines and showed a 25-fold range from the most sensitive to the most resistant line. It is concluded that the response of a cell to methotrexate is significantly influenced by the dissociation constant of its dihydrofolate reductase-methotrexate complex."}
{"id": "PMID:5190", "title": "Aflatoxin B1 metabolism to aflatoxicol and derivatives lethal to Bacillus subtilis GSY 1057 by rainbow trout (Salmo gairdneri) liver.", "content": "Aflatoxicol, R0, was isolated from Mt. Shasta strain rainbow trout (Salmo gairdneri), and liver homogenates were incubated with aflatoxin B1. Its identity was confirmed by mass, infrared, and ultraviolet spectrometry. The structure was identical to one of the diastereomers prepared by chemical reduction of aflatoxin B1. Aflatoxicol was apparently formed by a reduced nicotinamide adenine dinucleotide phosphate-dependent soluble enzyme of the 105,000 x g supernatant from rainbow trout. Aflatoxicol was not lethal in phosphate buffer to Bacillus subtilis GSY 1057 (metB4, hisA1, uvr-1) nor were aflatoxins B1, Q1, and B2. In the presence of reduced nicotinamide adenine dinucleotide phosphate and trout liver microsomes, aflatoxicol reduced the viability of B. subtilis. Aflatoxin B2, which lacks the vinyl ether present in the other compounds, could not be activated. The product of aflatoxin B1 activation by trout liver microsomes was sought after incubation of 14C-labeled aflatoxin B1. The radioactivity was found in unaltered aflatoxin B1 and in three extremely polar metabolites. The quantity of the new metabolites and the level of microbial lethality was reduced by addition of cytosine and cysteine to the incubation medium. The vinyl ether configuration was a structural requirement for activation, and this finding and the nature of the enzymatic reaction were consistent with the hypothesis that the compounds were metabolized to highly reactive and unstable electrophilic products which bound to nucleophiles such as cytosine and were lethal to B. subtilis. The formation of aflatoxicol as the major product of trout liver metabolism is of great significance considering that it could be activated to a lethal compound and that rainbow trout are one of the most sensitive species to aflatoxin B1-induced carcinoma.", "contents": "Aflatoxin B1 metabolism to aflatoxicol and derivatives lethal to Bacillus subtilis GSY 1057 by rainbow trout (Salmo gairdneri) liver. Aflatoxicol, R0, was isolated from Mt. Shasta strain rainbow trout (Salmo gairdneri), and liver homogenates were incubated with aflatoxin B1. Its identity was confirmed by mass, infrared, and ultraviolet spectrometry. The structure was identical to one of the diastereomers prepared by chemical reduction of aflatoxin B1. Aflatoxicol was apparently formed by a reduced nicotinamide adenine dinucleotide phosphate-dependent soluble enzyme of the 105,000 x g supernatant from rainbow trout. Aflatoxicol was not lethal in phosphate buffer to Bacillus subtilis GSY 1057 (metB4, hisA1, uvr-1) nor were aflatoxins B1, Q1, and B2. In the presence of reduced nicotinamide adenine dinucleotide phosphate and trout liver microsomes, aflatoxicol reduced the viability of B. subtilis. Aflatoxin B2, which lacks the vinyl ether present in the other compounds, could not be activated. The product of aflatoxin B1 activation by trout liver microsomes was sought after incubation of 14C-labeled aflatoxin B1. The radioactivity was found in unaltered aflatoxin B1 and in three extremely polar metabolites. The quantity of the new metabolites and the level of microbial lethality was reduced by addition of cytosine and cysteine to the incubation medium. The vinyl ether configuration was a structural requirement for activation, and this finding and the nature of the enzymatic reaction were consistent with the hypothesis that the compounds were metabolized to highly reactive and unstable electrophilic products which bound to nucleophiles such as cytosine and were lethal to B. subtilis. The formation of aflatoxicol as the major product of trout liver metabolism is of great significance considering that it could be activated to a lethal compound and that rainbow trout are one of the most sensitive species to aflatoxin B1-induced carcinoma."}
{"id": "PMID:5191", "title": "Xylanase (hemicellulase) activity in cell-free rumen fluid.", "content": "It has been shown that there is hemicellulase (xylanase) activity in cell-free filtrates of rumen liquor. This activity changes during the feeding cycle. The optimal pH and temperature for this activity have been found, as have the substrate-to-enzyme ratios. Many reagents, particularly heavy metal ions and phenols, inhibit the activity, but the activity is enhanced by reducing agents. No activity towards monosaccharides, disaccharides, or glycosides was found. The xylanase component was not stable, due to proteolytic enzymes in the rumen liquor, but could be purified by a variety of methods to give more-stable enzymes.", "contents": "Xylanase (hemicellulase) activity in cell-free rumen fluid. It has been shown that there is hemicellulase (xylanase) activity in cell-free filtrates of rumen liquor. This activity changes during the feeding cycle. The optimal pH and temperature for this activity have been found, as have the substrate-to-enzyme ratios. Many reagents, particularly heavy metal ions and phenols, inhibit the activity, but the activity is enhanced by reducing agents. No activity towards monosaccharides, disaccharides, or glycosides was found. The xylanase component was not stable, due to proteolytic enzymes in the rumen liquor, but could be purified by a variety of methods to give more-stable enzymes."}
{"id": "PMID:5194", "title": "Antitumor activity of equinatoxin.", "content": "Equinatoxin, a highly basic protein extracted from Actinia equina, causes an increase in the survival time of mice bearing the ascitic form of Ehrlich carcinoma, whereas it has no effect on L1210 leukaemia. When tested for in vitro cytotoxicity by the dye exclusion test, it shows a potent activity on both tumour cell lines, with ED50 of a few ng/ml. Higher concentrations produce an extensive lysis of the cells. The cytotoxic effects of Equinatoxin are inhibited by phospholipids, thus suggesting that its mechanism of action may be related to interactions with lipids or other charged components of cell membrane. The observed lack of in vivo activity against L1210 leukaemia presumably is due to poor systemic absorption of the protein and/or neutralization by serum factors.", "contents": "Antitumor activity of equinatoxin. Equinatoxin, a highly basic protein extracted from Actinia equina, causes an increase in the survival time of mice bearing the ascitic form of Ehrlich carcinoma, whereas it has no effect on L1210 leukaemia. When tested for in vitro cytotoxicity by the dye exclusion test, it shows a potent activity on both tumour cell lines, with ED50 of a few ng/ml. Higher concentrations produce an extensive lysis of the cells. The cytotoxic effects of Equinatoxin are inhibited by phospholipids, thus suggesting that its mechanism of action may be related to interactions with lipids or other charged components of cell membrane. The observed lack of in vivo activity against L1210 leukaemia presumably is due to poor systemic absorption of the protein and/or neutralization by serum factors."}
{"id": "PMID:5199", "title": "[Effect of ionic strength on the protection of DNA by histone F1 against the enzymatic activity of DNase I].", "content": "Studying the effect of ionic strength on DNA protection by histone F1 against DNase I has shown a maximum protection near 0,1 M NaCl. At this ionic strength, different results have been obtained by measuring the initial velocity or the amount of DNA hydrolysed at the end of the reaction.", "contents": "[Effect of ionic strength on the protection of DNA by histone F1 against the enzymatic activity of DNase I]. Studying the effect of ionic strength on DNA protection by histone F1 against DNase I has shown a maximum protection near 0,1 M NaCl. At this ionic strength, different results have been obtained by measuring the initial velocity or the amount of DNA hydrolysed at the end of the reaction."}
{"id": "PMID:5200", "title": "[Disadvantages of acid precipitation of proteins during the assay of blood glucose by the enzymatic glucose oxidase-peroxidase system].", "content": "In the enzymatic procedure for blood sugar by means of glucose oxidase, acid protein precipitation of blood by perchloric acid or trichloracetic acid liberated oxidizing substances, which enhanced the coloration density in oxidizing the reduced chromogen of the reaction mixture, independently of the hydrogen peroxide generated from glucose, and would give false high values of glycemia, if additional precautions had not been taken. These substances, increasing considerably with times and temperature of blood conservation, would be of peroxide nature, and would accumulate in red blood cells during their exposure to air.", "contents": "[Disadvantages of acid precipitation of proteins during the assay of blood glucose by the enzymatic glucose oxidase-peroxidase system]. In the enzymatic procedure for blood sugar by means of glucose oxidase, acid protein precipitation of blood by perchloric acid or trichloracetic acid liberated oxidizing substances, which enhanced the coloration density in oxidizing the reduced chromogen of the reaction mixture, independently of the hydrogen peroxide generated from glucose, and would give false high values of glycemia, if additional precautions had not been taken. These substances, increasing considerably with times and temperature of blood conservation, would be of peroxide nature, and would accumulate in red blood cells during their exposure to air."}
{"id": "PMID:5201", "title": "Evidence for a renal alpha-adrenergic receptor inhibiting renin release.", "content": "The mechanism by which clonidine suppresses renin release was investigated in conscious rats. This suppression was studied by means of selected autonomic interventions in conjunction with changes in sodium balance. Serum renin activity and direct arterial pressure were monitored. Clonidine administration suppressed basal (by 68-85%), diuretic-induced (by 89%), and sympathetic nervous system-mediated (by 75-100%) renin release. Cholinergic, ganglionic, and peripheral sympathetic neuronal blockade did not prevent this inhibitory effect of clonidine. These results indicate a peripheral site of action for suppression of renin release by clonidine. The alpha-adrenergic blocking drug phentolamine prevented clonidine suppression of renin release in sodium-depleted rats and was partially effective in normal rats. Phentolamine blocked the decrease in renin caused by clonidine in ganglion-blocked rats. Clozapine, a new neuroleptic agent with alpha-adrenergic blocking activity, or phenoxybenzamine blocked the effect of clonidine on renin release in both sodium-depleted and normal rats. After ganglionic blockade in sodium-depleted rats, clonidine caused a significantly greater suppression of renin release than did an equipressor dose of methoxamine. These data, combined with hemodynamic correlates, suggest that clonidine inhibits renin release by activation of an intrarenal alpha-adrenergic receptor.", "contents": "Evidence for a renal alpha-adrenergic receptor inhibiting renin release. The mechanism by which clonidine suppresses renin release was investigated in conscious rats. This suppression was studied by means of selected autonomic interventions in conjunction with changes in sodium balance. Serum renin activity and direct arterial pressure were monitored. Clonidine administration suppressed basal (by 68-85%), diuretic-induced (by 89%), and sympathetic nervous system-mediated (by 75-100%) renin release. Cholinergic, ganglionic, and peripheral sympathetic neuronal blockade did not prevent this inhibitory effect of clonidine. These results indicate a peripheral site of action for suppression of renin release by clonidine. The alpha-adrenergic blocking drug phentolamine prevented clonidine suppression of renin release in sodium-depleted rats and was partially effective in normal rats. Phentolamine blocked the decrease in renin caused by clonidine in ganglion-blocked rats. Clozapine, a new neuroleptic agent with alpha-adrenergic blocking activity, or phenoxybenzamine blocked the effect of clonidine on renin release in both sodium-depleted and normal rats. After ganglionic blockade in sodium-depleted rats, clonidine caused a significantly greater suppression of renin release than did an equipressor dose of methoxamine. These data, combined with hemodynamic correlates, suggest that clonidine inhibits renin release by activation of an intrarenal alpha-adrenergic receptor."}
{"id": "PMID:5202", "title": "Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia.", "content": "The rate of coronary flow reaching the oxygen-linited heart appears to be crucial in determining the myocardial tissue metabolic response. The tissue metabolic response to anoxia, well studied in hearts perfused with anoxic media, differs in many important ways from the response to ischemia. In regional ischemia (developing infarction) there is still a residual oxygen uptake which is reduced approximately to the same extent as the delivery of O2; there is also decreased delivery of substrates and decreased removal of CO2, H+, and lactate, with increased concentrations of these metabolites. Contents of hexose monophosphates rise rather than fall in anoxia. Measurements of glycolytic intermediates show an initial burst of accelerated glycolytic flux lasting less than 1 minute after coronary artery ligation; thereafter rates of flux decrease to control values or even less at 120 minutes. Relative inhibition of phosphofructokinase (PFK) activity may be explained by a slow rate of fall of ATP and a developing intracellular acidosis. In this model, glucose accounts for a greater part of the residual oxidative metabolism than does free fatty acid (FFA).", "contents": "Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia. The rate of coronary flow reaching the oxygen-linited heart appears to be crucial in determining the myocardial tissue metabolic response. The tissue metabolic response to anoxia, well studied in hearts perfused with anoxic media, differs in many important ways from the response to ischemia. In regional ischemia (developing infarction) there is still a residual oxygen uptake which is reduced approximately to the same extent as the delivery of O2; there is also decreased delivery of substrates and decreased removal of CO2, H+, and lactate, with increased concentrations of these metabolites. Contents of hexose monophosphates rise rather than fall in anoxia. Measurements of glycolytic intermediates show an initial burst of accelerated glycolytic flux lasting less than 1 minute after coronary artery ligation; thereafter rates of flux decrease to control values or even less at 120 minutes. Relative inhibition of phosphofructokinase (PFK) activity may be explained by a slow rate of fall of ATP and a developing intracellular acidosis. In this model, glucose accounts for a greater part of the residual oxidative metabolism than does free fatty acid (FFA)."}
{"id": "PMID:5203", "title": "Control of ionic permeabilities in normal and ischemic heart.", "content": "The major ionic conductances underlying electrical activity in cardiac tissues are described. The participation of electrogenic active transport in electrical phenomenon and the influence of metabolic inhibition on cardiac action potentials are briefly summarized. Some electrophysiological effects of lactate and acidosis, such as might be induced by ischemia, are described. In dog Purkinje fibers, lactate (20 mM pH 7.0) may induce transient periods of arrhythmias. Acidosis decreases rapid sodium conductance, slow calcium-sodium conductance, and anomalous and delayed rectifications in frog atrial fibers. CO2-induced acidosis (20% CO2, pH 6.6) may alter the repolarization phase of the action potential in dog Purkinje fibers, presumably because it decreases potassium conductance. Alterations consist of partial depolarizations (humps) that result in reexcitation of the fibers and lead to a maintained depolarization. It is proposed that acidosis induces a decrease in potassium conductance that can be responsible for ectopic foci causing arrhythmias during ischemia.", "contents": "Control of ionic permeabilities in normal and ischemic heart. The major ionic conductances underlying electrical activity in cardiac tissues are described. The participation of electrogenic active transport in electrical phenomenon and the influence of metabolic inhibition on cardiac action potentials are briefly summarized. Some electrophysiological effects of lactate and acidosis, such as might be induced by ischemia, are described. In dog Purkinje fibers, lactate (20 mM pH 7.0) may induce transient periods of arrhythmias. Acidosis decreases rapid sodium conductance, slow calcium-sodium conductance, and anomalous and delayed rectifications in frog atrial fibers. CO2-induced acidosis (20% CO2, pH 6.6) may alter the repolarization phase of the action potential in dog Purkinje fibers, presumably because it decreases potassium conductance. Alterations consist of partial depolarizations (humps) that result in reexcitation of the fibers and lead to a maintained depolarization. It is proposed that acidosis induces a decrease in potassium conductance that can be responsible for ectopic foci causing arrhythmias during ischemia."}
{"id": "PMID:5204", "title": "Cutaneous and muscular rasodilation in the canine hindlimb evoked by central stimulation.", "content": "Using stereotaxic procedures, we electrically stimulated specific sites in the hypothalamus and midbrain of anesthetized dogs pretreated with guanethidine and atropine methonitrate. A tract in which stimulation caused noncholinergic dilator responses in the hindlimbs was identified. The course of this trace was different from that subserving cholinergic vasodilation in the hindlimb musculature. In a number of experiments we studied the proportional distribution of blood flow to leg and paw. Responses restricted to the paw were regarded as occurring mainly in cutaneous vessels; those restricted to the leg were regarded as occurring mainly in the skeletal muscle vessels. Some dilator responses in both beds were abolished by intra-arterial administration of antihistamines: other dilator responses were abolished by intra-arterial injections of dopamine antagonists. Centrally evoked dilation of leg and paw vessels by noncholinergic pathways suggests physiological roles for these fibers in the regulation of cardiovascular function.", "contents": "Cutaneous and muscular rasodilation in the canine hindlimb evoked by central stimulation. Using stereotaxic procedures, we electrically stimulated specific sites in the hypothalamus and midbrain of anesthetized dogs pretreated with guanethidine and atropine methonitrate. A tract in which stimulation caused noncholinergic dilator responses in the hindlimbs was identified. The course of this trace was different from that subserving cholinergic vasodilation in the hindlimb musculature. In a number of experiments we studied the proportional distribution of blood flow to leg and paw. Responses restricted to the paw were regarded as occurring mainly in cutaneous vessels; those restricted to the leg were regarded as occurring mainly in the skeletal muscle vessels. Some dilator responses in both beds were abolished by intra-arterial administration of antihistamines: other dilator responses were abolished by intra-arterial injections of dopamine antagonists. Centrally evoked dilation of leg and paw vessels by noncholinergic pathways suggests physiological roles for these fibers in the regulation of cardiovascular function."}
{"id": "PMID:5205", "title": "Spinal adrenergic mechanisms regulating sympathetic outflow to blood vessels.", "content": "The role of descending spinal catecholamine (CA)-containing fibers in cardiovascular regulation was examined. Monoamine-containing fibers were visualized by fluorescence histochemical methods at the cervical, thoracic, and lumbar spinal segments. Two major groups of descending CA-containing axons were located in the lateral funiculus at the midcervical spinal level. At the thoracolumbar spinal segments CA-containing terminals were concentrated mostly around cells of the intermediolateral nucleus. In addition a distinct CA-containing fasciculus was observed at the level of the sympathetic nucleus which appeared to course toward the opposite site of the cord. To evaluate the role of the efferent CA-containing fibers, changes in heart rate, arterial pressure, femoral blood flow, and calculated peak vascular resistance were elicited by electrical stimulation of selected sites in the midcervical spinal cord. Although changes in femoral flow and arterial pressure were evoked from many midcervical sites, there was a distinct correlation between the magnitude of peak femoral resistance elevation and density of CA-containing axons activated. Furthermore, efferent spinal vasoconstrictor outflow to the hindlimbs crosses below the cervical level. This observation is in good agreement with fluorescence microscopy studies revealing CA-containing fibers which appear to decussate. Pharmacological studies also were undertaken to evaluate transmission in spinal vasopressor pathways. In these studies alpha-adrenergic receptor antagonists and agonists were perfused into the spinal subarachnoid space. Heart rate, arterial pressure, femoral flow, and femoral resistance responses elicited from efferent spinal pathways were significantly attenuated following superfusion of the spinal cord with the alpha-antagonists BE-2254 (HEAT) and phentolamine. It was shown that inhibition of the centrally evoked responses was due to actions of the alpha-antagonists at a spinal locus and not due to peripheral vascular alpha-receptor blockade. Spinal perfusion with the alpha-receptor agonist norepinephrine potentiated cardiovascular responses. Likewise, loading with the norepinephrine precursor 3,4-dihydroxy-L-phenylalanine (L-dopa) enhanced vasoconstrictor responses evoked in the cross-perfused hindlimb of p-chlorophenylalanine-pretreated cats. These observations support the idea that bulbospinal CA-containing fibers relay excitatory impulses to preganglionic vasoconstrictor neurons and that spinal alpha-adrenergic receptor activation is necessary for transmission of this information.", "contents": "Spinal adrenergic mechanisms regulating sympathetic outflow to blood vessels. The role of descending spinal catecholamine (CA)-containing fibers in cardiovascular regulation was examined. Monoamine-containing fibers were visualized by fluorescence histochemical methods at the cervical, thoracic, and lumbar spinal segments. Two major groups of descending CA-containing axons were located in the lateral funiculus at the midcervical spinal level. At the thoracolumbar spinal segments CA-containing terminals were concentrated mostly around cells of the intermediolateral nucleus. In addition a distinct CA-containing fasciculus was observed at the level of the sympathetic nucleus which appeared to course toward the opposite site of the cord. To evaluate the role of the efferent CA-containing fibers, changes in heart rate, arterial pressure, femoral blood flow, and calculated peak vascular resistance were elicited by electrical stimulation of selected sites in the midcervical spinal cord. Although changes in femoral flow and arterial pressure were evoked from many midcervical sites, there was a distinct correlation between the magnitude of peak femoral resistance elevation and density of CA-containing axons activated. Furthermore, efferent spinal vasoconstrictor outflow to the hindlimbs crosses below the cervical level. This observation is in good agreement with fluorescence microscopy studies revealing CA-containing fibers which appear to decussate. Pharmacological studies also were undertaken to evaluate transmission in spinal vasopressor pathways. In these studies alpha-adrenergic receptor antagonists and agonists were perfused into the spinal subarachnoid space. Heart rate, arterial pressure, femoral flow, and femoral resistance responses elicited from efferent spinal pathways were significantly attenuated following superfusion of the spinal cord with the alpha-antagonists BE-2254 (HEAT) and phentolamine. It was shown that inhibition of the centrally evoked responses was due to actions of the alpha-antagonists at a spinal locus and not due to peripheral vascular alpha-receptor blockade. Spinal perfusion with the alpha-receptor agonist norepinephrine potentiated cardiovascular responses. Likewise, loading with the norepinephrine precursor 3,4-dihydroxy-L-phenylalanine (L-dopa) enhanced vasoconstrictor responses evoked in the cross-perfused hindlimb of p-chlorophenylalanine-pretreated cats. These observations support the idea that bulbospinal CA-containing fibers relay excitatory impulses to preganglionic vasoconstrictor neurons and that spinal alpha-adrenergic receptor activation is necessary for transmission of this information."}
{"id": "PMID:5207", "title": "Cellular basis for increased sensitivity of vascular smooth muscle in spontaneously hypertensive rats.", "content": "There is evidence that hypersensitivity of vascular muscle to neurotransmitters contributes to the development of hypertension. Comparison of the caudal arteries of spontaneously hypertensive rats (SHR) and their genetically related Kyoto-Wistar normotensive control rats (KNR) showed that although there is no difference in membrane potential under unstimulated conditions, greater depolarization of the SHR vascular muscle cells by norepinephrine occurs at concentrations which cause greater contraction. The mechanism for the increased depolarization and resulting increase in contraction appears to be a lower intracellular potassium ion activity in SHR vascular muscle cells, which results in a lower contribution of potassium gradient to membrane potential. Experiments to determine the sensitivity of isolated, dispersed chick omphalomesenteric vascular muscle cells to neurotransmitters showed remarkably low thresholds to the neutransmitters norepinephrine, serotonin, and acetylcholine, but not potassium chloride. The high sensitivity of isolated cells to neurotransmitters suggests that factors in the intact vessel may cause thresholds to be high, possibly implying that alterations in a neurotrophic mechanism might be responsible for changes in vascular muscle sensitivity in situ.", "contents": "Cellular basis for increased sensitivity of vascular smooth muscle in spontaneously hypertensive rats. There is evidence that hypersensitivity of vascular muscle to neurotransmitters contributes to the development of hypertension. Comparison of the caudal arteries of spontaneously hypertensive rats (SHR) and their genetically related Kyoto-Wistar normotensive control rats (KNR) showed that although there is no difference in membrane potential under unstimulated conditions, greater depolarization of the SHR vascular muscle cells by norepinephrine occurs at concentrations which cause greater contraction. The mechanism for the increased depolarization and resulting increase in contraction appears to be a lower intracellular potassium ion activity in SHR vascular muscle cells, which results in a lower contribution of potassium gradient to membrane potential. Experiments to determine the sensitivity of isolated, dispersed chick omphalomesenteric vascular muscle cells to neurotransmitters showed remarkably low thresholds to the neutransmitters norepinephrine, serotonin, and acetylcholine, but not potassium chloride. The high sensitivity of isolated cells to neurotransmitters suggests that factors in the intact vessel may cause thresholds to be high, possibly implying that alterations in a neurotrophic mechanism might be responsible for changes in vascular muscle sensitivity in situ."}
{"id": "PMID:5208", "title": "Partial purification of a high molecular weight renin from hog kidney.", "content": "Previous investigators have reported finding a high molecular weight (HMW) renin in various species which is activated by acidification. Two laboratories have reported that a decrease in molecular weight of the renin accompanies the acidification step. This report describes the partial purification of an HMW renin from hog kidney extracts which had previously been acidified to pH 2.5. The HMW renin, with a molecular weight of 57,000-59,000, constitutes only a small, relatively constant fraction of the total renin isolated. Omission of the acidification step or initial acidification to pH 1.6 does not change the amount of HMW renin significantly. The HMW renin attacks the protein substrate to produce angiotensin at about one-fourth the rate expected, based upon the rate at which it cleaves the tetradecapeptide substrate or a model nonapeptide substrate. It is inactivated by antiserum to hog kidney renin prepared in dogs. It is less stable than hog renin when stored at 0 degrees C. The HMW renin has a pH optimum between 6.5 and 7.0. It is not activated by acidification to pH 3, nor by tryptic or peptic digestion. We have been unable to activate HMW renin or to change its molecular weight by procedures reported by other investigators and therefore conclude that the HMW renin differs from material previously reported and may be an isoenzyme of renin.", "contents": "Partial purification of a high molecular weight renin from hog kidney. Previous investigators have reported finding a high molecular weight (HMW) renin in various species which is activated by acidification. Two laboratories have reported that a decrease in molecular weight of the renin accompanies the acidification step. This report describes the partial purification of an HMW renin from hog kidney extracts which had previously been acidified to pH 2.5. The HMW renin, with a molecular weight of 57,000-59,000, constitutes only a small, relatively constant fraction of the total renin isolated. Omission of the acidification step or initial acidification to pH 1.6 does not change the amount of HMW renin significantly. The HMW renin attacks the protein substrate to produce angiotensin at about one-fourth the rate expected, based upon the rate at which it cleaves the tetradecapeptide substrate or a model nonapeptide substrate. It is inactivated by antiserum to hog kidney renin prepared in dogs. It is less stable than hog renin when stored at 0 degrees C. The HMW renin has a pH optimum between 6.5 and 7.0. It is not activated by acidification to pH 3, nor by tryptic or peptic digestion. We have been unable to activate HMW renin or to change its molecular weight by procedures reported by other investigators and therefore conclude that the HMW renin differs from material previously reported and may be an isoenzyme of renin."}
{"id": "PMID:5209", "title": "Vasodilator administration in the presence of beta-adrenergic blockade.", "content": "To explore the possibility that the presence of propranolol-induced beta-adrenergic blockade might have an adverse effect upon homeostatic circulatory reflexes activated by the administration of a potent vasodilator agent, arterial blood pressure and pulse rate response to rapid intravenous diazoxide injection was monitored before and after pretreatment with propranolol in ten hypertensive patients. It appeared that beta-adrenergic blockade had no clinically significant effect on the magnitude of hypotension or the degree of heart rate acceleration induced by the administration of the potent vasodilator diazoxide. This reflex vasodilator-induced cardio-acceleration after propranolol adminstration could be the result of incomplete blockade of endogenously released neurotransmitter, inhibition of the parasympathetic nervous system, or a direct pharmacologic action of diazoxide. Diazoxide administration to hypertensive patients in the presence of beta-adrenergic blockade was not associated with any clinically significant hemodynamic consequences.", "contents": "Vasodilator administration in the presence of beta-adrenergic blockade. To explore the possibility that the presence of propranolol-induced beta-adrenergic blockade might have an adverse effect upon homeostatic circulatory reflexes activated by the administration of a potent vasodilator agent, arterial blood pressure and pulse rate response to rapid intravenous diazoxide injection was monitored before and after pretreatment with propranolol in ten hypertensive patients. It appeared that beta-adrenergic blockade had no clinically significant effect on the magnitude of hypotension or the degree of heart rate acceleration induced by the administration of the potent vasodilator diazoxide. This reflex vasodilator-induced cardio-acceleration after propranolol adminstration could be the result of incomplete blockade of endogenously released neurotransmitter, inhibition of the parasympathetic nervous system, or a direct pharmacologic action of diazoxide. Diazoxide administration to hypertensive patients in the presence of beta-adrenergic blockade was not associated with any clinically significant hemodynamic consequences."}
{"id": "PMID:5210", "title": "A modified inactivation-inhibition method for determining the serum activity of alkaline phosphatase isoenzymes.", "content": "A procedure using heat inactivation and L-phenylalanine inhibition to quantitate the activities of bone, liver and intestinal alkaline phosphatase isoenzymes in human serum was confirmed by alkaline phosphatase isoenzyme analysis using an electrophoretic procedure. The results of this assay were compared with the radionuclear 85Sr test, and gamma-glutamyl transpeptidase activity in a group of patients with hepatobiliary and bone diseases.", "contents": "A modified inactivation-inhibition method for determining the serum activity of alkaline phosphatase isoenzymes. A procedure using heat inactivation and L-phenylalanine inhibition to quantitate the activities of bone, liver and intestinal alkaline phosphatase isoenzymes in human serum was confirmed by alkaline phosphatase isoenzyme analysis using an electrophoretic procedure. The results of this assay were compared with the radionuclear 85Sr test, and gamma-glutamyl transpeptidase activity in a group of patients with hepatobiliary and bone diseases."}
{"id": "PMID:5211", "title": "A sensitive automated colorimetric method for the determination of serum gamma-glutamyl transpeptidase.", "content": "A highly sensitive and accurate automated method using a Technicon Autoanalyzer AAII was developed for the determination of human serum gamma-glutamyl transpeptidase. gamma-L-Glutamyl-p-nitroanilide added as substrate was split to p-nitroaniline and the gamma-glutamyl group was trapped by glycylglycine in Ammediol/HC1 buffer solution. Liberated p-nitroaniline was diazotized and converted by Tsuda Reagent (N,N-(diethyl)-N'-(1-naphthyl) ethylendiamine) to an azo-dye possessing an absorbance maximum at 550 nm. This new method of determination, using the conversion of p-nitroaniline to azo-dye, was found to be 7 times more sensitive as compared to the conventional direct p-nitroaniline determination method [1]. This method requires only 0.1 ml lerum and permits 60 determinations per hour.", "contents": "A sensitive automated colorimetric method for the determination of serum gamma-glutamyl transpeptidase. A highly sensitive and accurate automated method using a Technicon Autoanalyzer AAII was developed for the determination of human serum gamma-glutamyl transpeptidase. gamma-L-Glutamyl-p-nitroanilide added as substrate was split to p-nitroaniline and the gamma-glutamyl group was trapped by glycylglycine in Ammediol/HC1 buffer solution. Liberated p-nitroaniline was diazotized and converted by Tsuda Reagent (N,N-(diethyl)-N'-(1-naphthyl) ethylendiamine) to an azo-dye possessing an absorbance maximum at 550 nm. This new method of determination, using the conversion of p-nitroaniline to azo-dye, was found to be 7 times more sensitive as compared to the conventional direct p-nitroaniline determination method [1]. This method requires only 0.1 ml lerum and permits 60 determinations per hour."}
{"id": "PMID:5213", "title": "Suppression of experimental allergic encephalomyelitis in guinea-pigs with poly-L-lysine.", "content": "Poly-L-lysin (PLL) given subcutaneously in a dose of 3 mg/day suppresses experimental allergic encephalomyelitis in guinea-pigs. The suppressive effect of PLL can still be demonstrated when administration is begun 8 days post-immunization. The effect is disease- and species-specific since PLL (3 mg/day) does not suppress experimental allergic orchitis in guinea-pigs, nor does it suppress EAE in rats (1-5 mg/day). PLL (0-2 mg/day) does not decrease the severity of graft-versus-host disease (GVH) in mice as judged by the spleen/body weight assay.", "contents": "Suppression of experimental allergic encephalomyelitis in guinea-pigs with poly-L-lysine. Poly-L-lysin (PLL) given subcutaneously in a dose of 3 mg/day suppresses experimental allergic encephalomyelitis in guinea-pigs. The suppressive effect of PLL can still be demonstrated when administration is begun 8 days post-immunization. The effect is disease- and species-specific since PLL (3 mg/day) does not suppress experimental allergic orchitis in guinea-pigs, nor does it suppress EAE in rats (1-5 mg/day). PLL (0-2 mg/day) does not decrease the severity of graft-versus-host disease (GVH) in mice as judged by the spleen/body weight assay."}
{"id": "PMID:5215", "title": "Reactions to cigarettes as a function of nicotine and \"tar\".", "content": "Experiments carried out to examine the effects of nicotine and \"tar\" on the extent of and subjective reactions to cigarette smoking. It was confirmed that smokers rate commercial, low-nicotine cigarettes as less \"strong\" and less \"satisfying\" than their usual brands. Since such cigarettes deliver reduced amounts of tar as well as of nicotine, an experiment to distinguish between the two was carried out with special cigarettes. Ratings of \"strength\" were directly related to nicotine but were not affected by tar. The numbers of cigarettes smoked fell slightly as their estimated delivery of nicotine increased, but tar had no effect on this index. The urinary excretion of nicotine was correlated with the rated yields of nicotine for the different cigarettes, but there was also evidence that subjects tended to adjust their manner of smoking so as to titrate their doses of nicotine. The results are interpreted as indicating a role for nicotine, but not for tar, in the maintenance of cigarette smoking behavior, and as support for the view that less harmful cigarettes should have a high yield of nicotine relative to tar.", "contents": "Reactions to cigarettes as a function of nicotine and \"tar\". Experiments carried out to examine the effects of nicotine and \"tar\" on the extent of and subjective reactions to cigarette smoking. It was confirmed that smokers rate commercial, low-nicotine cigarettes as less \"strong\" and less \"satisfying\" than their usual brands. Since such cigarettes deliver reduced amounts of tar as well as of nicotine, an experiment to distinguish between the two was carried out with special cigarettes. Ratings of \"strength\" were directly related to nicotine but were not affected by tar. The numbers of cigarettes smoked fell slightly as their estimated delivery of nicotine increased, but tar had no effect on this index. The urinary excretion of nicotine was correlated with the rated yields of nicotine for the different cigarettes, but there was also evidence that subjects tended to adjust their manner of smoking so as to titrate their doses of nicotine. The results are interpreted as indicating a role for nicotine, but not for tar, in the maintenance of cigarette smoking behavior, and as support for the view that less harmful cigarettes should have a high yield of nicotine relative to tar."}
{"id": "PMID:5251", "title": "Effect of beta-adrenergic agonists aerosolized by freon propellant on tracheal mucous velocity and cardiac output.", "content": "The present study was designed to assess the effects of two beta-adrenergic agonists, isoproterenol sulfate and carbuterol hydrochloride, and aerosolized Freon propellant (a mixture of Freon II, Freon 12, and Freon 114) on tracheal mucous velocity and cardiac output in anesthetized dogs. Five groups of ten animals each received the following dosages of aerosols: Freon, 20 puffs; isoproterenol, four puffs; carbuterol, four puffs; isoproterenol, 20 puffs; and carbuterol, 20 puffs. The puff was delivered by a standard metered aerosol; each puff of isoproterenol spray contained 75 mug of isoproterenol sulfate, and each puff of carbuterol spray contained 100 mug of carbuterol hydrochloride. Tracheal mucous velocity was not changed by receiving Freon, but administration of both isoproterenol and carbuterol caused a significant increase in this measurement, with peak increases ranging from 74 to 111 percent above control values. The duration of action for four and 20 puffs of isoproterenol and for four puffs of carbuterol was two hours. Twenty puffs of carbuterol increased tracheal mucous velocity for three hours. Administration of carbuterol effected a slightly larger increase in cardiac output than isoproterenol. The duration of action for the increased cardiac output was shorter than the duration of action for the increased tracheal mucous velocity. These studies indicate that beta-adrenergic agonists may have an important role in improving mucous transport in patients with chronic obstructive pulmonary disease in whom mucociliary clearance is depressed.", "contents": "Effect of beta-adrenergic agonists aerosolized by freon propellant on tracheal mucous velocity and cardiac output. The present study was designed to assess the effects of two beta-adrenergic agonists, isoproterenol sulfate and carbuterol hydrochloride, and aerosolized Freon propellant (a mixture of Freon II, Freon 12, and Freon 114) on tracheal mucous velocity and cardiac output in anesthetized dogs. Five groups of ten animals each received the following dosages of aerosols: Freon, 20 puffs; isoproterenol, four puffs; carbuterol, four puffs; isoproterenol, 20 puffs; and carbuterol, 20 puffs. The puff was delivered by a standard metered aerosol; each puff of isoproterenol spray contained 75 mug of isoproterenol sulfate, and each puff of carbuterol spray contained 100 mug of carbuterol hydrochloride. Tracheal mucous velocity was not changed by receiving Freon, but administration of both isoproterenol and carbuterol caused a significant increase in this measurement, with peak increases ranging from 74 to 111 percent above control values. The duration of action for four and 20 puffs of isoproterenol and for four puffs of carbuterol was two hours. Twenty puffs of carbuterol increased tracheal mucous velocity for three hours. Administration of carbuterol effected a slightly larger increase in cardiac output than isoproterenol. The duration of action for the increased cardiac output was shorter than the duration of action for the increased tracheal mucous velocity. These studies indicate that beta-adrenergic agonists may have an important role in improving mucous transport in patients with chronic obstructive pulmonary disease in whom mucociliary clearance is depressed."}
{"id": "PMID:5253", "title": "Effect of nafenopin (SU-13437) on liver function. Influence on the hepatic transport of phenolphthalein glucuronide and chlorothiazide.", "content": "In rats treated with the hypolipidemic drug, nafenopin (NP), for 2 days the biliary excretion of phenolphthalein glucuronide (PPG) was markedly decreased, while in contrast that of chlorothiazide (CTZ) was enhanced. This suggests the existence of independent hepatic transport mechanisms for these two anions. For both PPG and CTZ blood disappearance curves showed an initial, rapid phase followed by a second, slow phase. The rapid phase for both compounds is affected only slightly by pretreatment with NP. Therefore, it is inferred that suppression of biliary excretion was attributable mainly to impairment of the liver-to-bile transport process. The increased bile flow induced by NP treatment was previously shown to be related to the biliary excretion of NP and its metabolites. Inhibition of NP choleresis by PPG may involve competition for biliary transport of these compounds. The marked hepatomegaly and choleresis seen after NP pretreatment was more evident in male rats than in females.", "contents": "Effect of nafenopin (SU-13437) on liver function. Influence on the hepatic transport of phenolphthalein glucuronide and chlorothiazide. In rats treated with the hypolipidemic drug, nafenopin (NP), for 2 days the biliary excretion of phenolphthalein glucuronide (PPG) was markedly decreased, while in contrast that of chlorothiazide (CTZ) was enhanced. This suggests the existence of independent hepatic transport mechanisms for these two anions. For both PPG and CTZ blood disappearance curves showed an initial, rapid phase followed by a second, slow phase. The rapid phase for both compounds is affected only slightly by pretreatment with NP. Therefore, it is inferred that suppression of biliary excretion was attributable mainly to impairment of the liver-to-bile transport process. The increased bile flow induced by NP treatment was previously shown to be related to the biliary excretion of NP and its metabolites. Inhibition of NP choleresis by PPG may involve competition for biliary transport of these compounds. The marked hepatomegaly and choleresis seen after NP pretreatment was more evident in male rats than in females."}
{"id": "PMID:5254", "title": "Distribution and biliary excretion products of di-2-ethylhexyl phthalate in rainbow trout.", "content": "After 24-hr exposures of rainbow trout to 0.5 ppm of di-2-ethylhexyl [14C]phthalate, one-half of the radioactivity present in the fish was localized in the bile. The bile was pooled and fractionated by selective solvent extraction before and after beta-glucuronidase hydrolysis. Individual radioactive compounds were further separated and characterized by thin-layer chromatography. Gas chromatography-mass spectrometry was used to confirm the results of thin-layer chromatographic analysis. These procedures demonstrated that bile contained a number of DEHP metabolites, but only about 1% of unchanged DEHP. The major metabolite, mono-2-ethylhexyl phthalate glucuronide accounted for 72% of the total bile radioactivity. The remaining bile radioactivity was found to be present as phthalic acid glucuronide, mono-2-ethylhexyl phthalate and two partially characterized polar metabolites.", "contents": "Distribution and biliary excretion products of di-2-ethylhexyl phthalate in rainbow trout. After 24-hr exposures of rainbow trout to 0.5 ppm of di-2-ethylhexyl [14C]phthalate, one-half of the radioactivity present in the fish was localized in the bile. The bile was pooled and fractionated by selective solvent extraction before and after beta-glucuronidase hydrolysis. Individual radioactive compounds were further separated and characterized by thin-layer chromatography. Gas chromatography-mass spectrometry was used to confirm the results of thin-layer chromatographic analysis. These procedures demonstrated that bile contained a number of DEHP metabolites, but only about 1% of unchanged DEHP. The major metabolite, mono-2-ethylhexyl phthalate glucuronide accounted for 72% of the total bile radioactivity. The remaining bile radioactivity was found to be present as phthalic acid glucuronide, mono-2-ethylhexyl phthalate and two partially characterized polar metabolites."}
{"id": "PMID:5255", "title": "Binding of radioactivity from (14C)thiourea to rat lung protein.", "content": "Binding of radioactivity from [14C]thiourea (TU) to rat lung protein was found to occur in vitro. Two binding sites are present. One possesses low affinity/high capacity while the other is characterized by high affinity/low capacity. In vitro binding of [14C]TU to lung protein can be antagonized by the presence of either unlabeled congeners (alpha-napthylthiourea or phenylthiourea) or thiol-containing compounds (cysteine, reduced glutathione). Conversely, depletion of lung-reduced glutathione by means of diethyl maleate administration results in elevated protein binding. Prior administration (24 hr) of a sublethal dose of TU (which renders tolerance to a subsequent lethal dose in vivo) results in a decrease in in vitro binding of radioactivity from [14C)TU to lung protein. In addition, immature rats, which are less sensitive to the edematogenic effect of TU, bind less radioactivity from [14C]TU to lung protein when the drug is administered in vivo. These results suggest a correlation between [14C]TU binding to lung protein and the pathophysiological effect of the drug in the lung.", "contents": "Binding of radioactivity from (14C)thiourea to rat lung protein. Binding of radioactivity from [14C]thiourea (TU) to rat lung protein was found to occur in vitro. Two binding sites are present. One possesses low affinity/high capacity while the other is characterized by high affinity/low capacity. In vitro binding of [14C]TU to lung protein can be antagonized by the presence of either unlabeled congeners (alpha-napthylthiourea or phenylthiourea) or thiol-containing compounds (cysteine, reduced glutathione). Conversely, depletion of lung-reduced glutathione by means of diethyl maleate administration results in elevated protein binding. Prior administration (24 hr) of a sublethal dose of TU (which renders tolerance to a subsequent lethal dose in vivo) results in a decrease in in vitro binding of radioactivity from [14C)TU to lung protein. In addition, immature rats, which are less sensitive to the edematogenic effect of TU, bind less radioactivity from [14C]TU to lung protein when the drug is administered in vivo. These results suggest a correlation between [14C]TU binding to lung protein and the pathophysiological effect of the drug in the lung."}
{"id": "PMID:5256", "title": "Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver.", "content": "The hepatic disposition of four chlorinated biphenyls was studied in isolated perfused rat liver preparations perfused with 30% rat blood. Biliary excretion of 14C-labeled 4-chlorobiphenyl (1-CB): 4,4'-dichlorobiphenyl (2-CB): 2,4,5,2',5'-pentachlorobiphenyl (5-CB) and 2,4,5,2',5'-hexachlorobiphenyl (6-CB) appeared to be inversely related to increased chlorination. Each of the compounds was rapidly taken up by the liver from the circulating perfusate. After 4 hr of perfusion, biliary excretion of 14C from 1-CB, 2-CB, 5-CB, and 6-CB was 48.2, 29.6, 20.5, and 1.3% of total dose, respectively. For 1-CB, this rate of biliary elimination represents a maximum perfusate/bile ratio of 107. About 97% of the label in the bile from 1-CB experiments was in the form of metabolites. Biliary excretion of 1-CB was biphasic: an initial rapid phase (t 1/2 = 13 min) was followed by a slower second phase (t 1/2 = 122 min). When the metabolites of 1-CB were added to the perfusate, biliary excretion of these metabolites was monophasic; t 1/2 = 120 min, which corresponded to the slower phase observed when the parent compound was presented to the liver. 1-CB disappeared from the perfusate via a biphasic process. Metabolites of 1-CB effused into the perfusate immediately after the initial rapid uptake of 1-CB by the liver, and the recirculating pool of metabolites was eliminated in the bile by the slow postsynthetic phase of biliary elimination. Less than 2% of 1-CB was present as the parent compound in the perfusion system after 4 hr of perfusion. These findings indicate that the metabolism of 1-CB is not the limiting factor in the hepatic disposition of 1-CB and that the circulating metabolites of 1-CB effusing from the liver might be the major source for urinary excretion.", "contents": "Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver. The hepatic disposition of four chlorinated biphenyls was studied in isolated perfused rat liver preparations perfused with 30% rat blood. Biliary excretion of 14C-labeled 4-chlorobiphenyl (1-CB): 4,4'-dichlorobiphenyl (2-CB): 2,4,5,2',5'-pentachlorobiphenyl (5-CB) and 2,4,5,2',5'-hexachlorobiphenyl (6-CB) appeared to be inversely related to increased chlorination. Each of the compounds was rapidly taken up by the liver from the circulating perfusate. After 4 hr of perfusion, biliary excretion of 14C from 1-CB, 2-CB, 5-CB, and 6-CB was 48.2, 29.6, 20.5, and 1.3% of total dose, respectively. For 1-CB, this rate of biliary elimination represents a maximum perfusate/bile ratio of 107. About 97% of the label in the bile from 1-CB experiments was in the form of metabolites. Biliary excretion of 1-CB was biphasic: an initial rapid phase (t 1/2 = 13 min) was followed by a slower second phase (t 1/2 = 122 min). When the metabolites of 1-CB were added to the perfusate, biliary excretion of these metabolites was monophasic; t 1/2 = 120 min, which corresponded to the slower phase observed when the parent compound was presented to the liver. 1-CB disappeared from the perfusate via a biphasic process. Metabolites of 1-CB effused into the perfusate immediately after the initial rapid uptake of 1-CB by the liver, and the recirculating pool of metabolites was eliminated in the bile by the slow postsynthetic phase of biliary elimination. Less than 2% of 1-CB was present as the parent compound in the perfusion system after 4 hr of perfusion. These findings indicate that the metabolism of 1-CB is not the limiting factor in the hepatic disposition of 1-CB and that the circulating metabolites of 1-CB effusing from the liver might be the major source for urinary excretion."}
{"id": "PMID:5258", "title": "(14C)Methylphenidate hydrochloride. Studies on disposition in rat brain.", "content": "Studies with [14C]methylphenidate-HCl were carried out in rats administered the drug intravenously or intraperitoneally. Levels of total radioactivity and parent drug were measured in plasma, brain, and certain brain regions up to 6 hr after dosing. The intravenous route of administration was characterized by rapid entry into brain; during the first half hour, brain levels were 3- to 6-fold higher than those obtained by the intraperitoneal route. At later time periods, brain and plasma concentration for both routes were comparable, and the decline of drug concentrations in brain paralleled that in plasma. No significant variance was found in regional distribution of drug in brain. Whereas the major fraction of circulating drug consisted of metabolites, predominantly unchanged drug was found in brain. After intravenous injection of [14C]ritalinic acid (the major metabolite of methylphenidate), no substantial concentrations were found in brain.", "contents": "(14C)Methylphenidate hydrochloride. Studies on disposition in rat brain. Studies with [14C]methylphenidate-HCl were carried out in rats administered the drug intravenously or intraperitoneally. Levels of total radioactivity and parent drug were measured in plasma, brain, and certain brain regions up to 6 hr after dosing. The intravenous route of administration was characterized by rapid entry into brain; during the first half hour, brain levels were 3- to 6-fold higher than those obtained by the intraperitoneal route. At later time periods, brain and plasma concentration for both routes were comparable, and the decline of drug concentrations in brain paralleled that in plasma. No significant variance was found in regional distribution of drug in brain. Whereas the major fraction of circulating drug consisted of metabolites, predominantly unchanged drug was found in brain. After intravenous injection of [14C]ritalinic acid (the major metabolite of methylphenidate), no substantial concentrations were found in brain."}
{"id": "PMID:5257", "title": "The absorption, distribution, and excretion in mice of a quinolinemethanol antimalarial, 2,8-bis(trifluoromethyl)-4-(1-hydroxy-3-(N-t-butylamino)propyl)quinoline phosphate (WR 184,806).", "content": "Approximately 75% of the radioactivity derived from WR 184806-14C was excreted in the feces with the remainder in the urine after po administration. At least 77-85% of the dose was absorbed by 2-8 hr; lungs, liver, skeletal muscle, kidneys, small intestine (less contents) and residual carcass were major sites of deposition of total radioactivity. Within these tissues the radioactivity present was predominantly as WR 184,806 rather than its metabolites. Peak blood plasma levels of WR 184,806 occurred at 2-4 and 7-10 hr. The peak erythrocyte level of WR 184,806 occurred at 6 hr. The presence in the urine and feces of unchanged WR 184,806 was confirmed by thin-layer chromatography and inverse isotope dilution.", "contents": "The absorption, distribution, and excretion in mice of a quinolinemethanol antimalarial, 2,8-bis(trifluoromethyl)-4-(1-hydroxy-3-(N-t-butylamino)propyl)quinoline phosphate (WR 184,806). Approximately 75% of the radioactivity derived from WR 184806-14C was excreted in the feces with the remainder in the urine after po administration. At least 77-85% of the dose was absorbed by 2-8 hr; lungs, liver, skeletal muscle, kidneys, small intestine (less contents) and residual carcass were major sites of deposition of total radioactivity. Within these tissues the radioactivity present was predominantly as WR 184,806 rather than its metabolites. Peak blood plasma levels of WR 184,806 occurred at 2-4 and 7-10 hr. The peak erythrocyte level of WR 184,806 occurred at 6 hr. The presence in the urine and feces of unchanged WR 184,806 was confirmed by thin-layer chromatography and inverse isotope dilution."}
{"id": "PMID:5259", "title": "Oxisuran metabolism in pigs.", "content": "The fate of oxisuran in the pig was studied with 14C-labeled drug to quantify its biotransformation and disposition. Despite interanimal differences, it was clear that the compound absorbed rapidly and biotransformed extensively to metabolites which were excreted principally in urine rather than in feces. Direct attacks upon oxisuran involved reduction to diastereo-isomeric oxisuran alcohol sulfoxides and oxidation to oxisuran sulfone. Subsequently, the oxisuran alcohol sulfoxides were reduced to a sulfide and oxidized to a sulfone. Phase II reactions appeared to be limited to sulfation of oxisuran alcohol sulfoxides and oxisuran alcohol sulfone. Pharmacokinetics were investigated for oxisuran and its metabolites.", "contents": "Oxisuran metabolism in pigs. The fate of oxisuran in the pig was studied with 14C-labeled drug to quantify its biotransformation and disposition. Despite interanimal differences, it was clear that the compound absorbed rapidly and biotransformed extensively to metabolites which were excreted principally in urine rather than in feces. Direct attacks upon oxisuran involved reduction to diastereo-isomeric oxisuran alcohol sulfoxides and oxidation to oxisuran sulfone. Subsequently, the oxisuran alcohol sulfoxides were reduced to a sulfide and oxidized to a sulfone. Phase II reactions appeared to be limited to sulfation of oxisuran alcohol sulfoxides and oxisuran alcohol sulfone. Pharmacokinetics were investigated for oxisuran and its metabolites."}
{"id": "PMID:5261", "title": "Qualitative metabolic fate of phenoxybenzamine in rat, dog, and man. Use of 15N-labeling.", "content": "Administration of an equimolar mixture of unlabeled and 15N-labeled phenoxybenzamine to rats and dogs facilitated identification of urinary metabolites by gas chromatography/chemical-ionization mass spectrometry by virtue of the the conspicuous equal-intensity ion pairs produced. By use of this technique N-benzyl-N-phenoxyisopropylamine (III), N-benzyl-N-(p-hydroxy-phenoxyisopropyl)amine (IV), and 2-benzylamino-1-propanol (VI) were identified as metabolites in rats. Phenoxyisopropylamine (V) as well as III and IV were identified in dogs. Compound IV was identified in humans under clinical treatment with phenoxybenzamine. The metabolites were screened for cardiovascular activity in rats. Compound III had weak alpha-adrenergic blocking activity and V elicited a hypertensive response.", "contents": "Qualitative metabolic fate of phenoxybenzamine in rat, dog, and man. Use of 15N-labeling. Administration of an equimolar mixture of unlabeled and 15N-labeled phenoxybenzamine to rats and dogs facilitated identification of urinary metabolites by gas chromatography/chemical-ionization mass spectrometry by virtue of the the conspicuous equal-intensity ion pairs produced. By use of this technique N-benzyl-N-phenoxyisopropylamine (III), N-benzyl-N-(p-hydroxy-phenoxyisopropyl)amine (IV), and 2-benzylamino-1-propanol (VI) were identified as metabolites in rats. Phenoxyisopropylamine (V) as well as III and IV were identified in dogs. Compound IV was identified in humans under clinical treatment with phenoxybenzamine. The metabolites were screened for cardiovascular activity in rats. Compound III had weak alpha-adrenergic blocking activity and V elicited a hypertensive response."}
{"id": "PMID:5260", "title": "Metabolism of trans-stilbene in rabbits and rats.", "content": "The biotransformation of intramuscularly administered 14C-labeled trans-stilbene was investigated in both rabbits and rats. In rabbits radioactivity was excreted (78.8% in 17 days) almost exclusively in the urine. In rats, feces accounted for more than half of the total excretion (80.3% in 19 days). Hydroxylated metabolites in urine and feces were identified by thin-layer chromatography and quantitated by liquid scintillation counting. They were 4-hydroxy and 4,4'-dihydroxystilbene, and the two monomethyl ethers of 3,4-dihydroxystilbene and 4,4'-dihydroxybibenzyl. In addition, four polyhydroxylated metabolites of stilbene and bibenzyl were identified in rat urine by comparison of gas-liquid chromatography retention times of their silyl derivatives with synthetic reference compounds. They were 3,4,4'-trihydroxystilbene, and 3,4-dihydroxy-, 3,4,4'=trihydroxy-, and 3,4,3',4'-tetrahydroxybibenzyl. Oxidative cleavage of trans-stilbene to benzoic acid and 4-hydroxy- and 3,4-dihydroxybenzoic acid was established by the presence of both the free acids and conjugates of these compounds in both rabbit and rat urine. Their glycine conjugates were identified by thin-layer chromatography and quantitated by reverse isotope dilution procedures from unhydrolyzed rabbit and rat urine. Percentages obtained indicate that cleavage of trans-stilbene is more extensive in rabbits (9.5%) than in rats (2.7%).", "contents": "Metabolism of trans-stilbene in rabbits and rats. The biotransformation of intramuscularly administered 14C-labeled trans-stilbene was investigated in both rabbits and rats. In rabbits radioactivity was excreted (78.8% in 17 days) almost exclusively in the urine. In rats, feces accounted for more than half of the total excretion (80.3% in 19 days). Hydroxylated metabolites in urine and feces were identified by thin-layer chromatography and quantitated by liquid scintillation counting. They were 4-hydroxy and 4,4'-dihydroxystilbene, and the two monomethyl ethers of 3,4-dihydroxystilbene and 4,4'-dihydroxybibenzyl. In addition, four polyhydroxylated metabolites of stilbene and bibenzyl were identified in rat urine by comparison of gas-liquid chromatography retention times of their silyl derivatives with synthetic reference compounds. They were 3,4,4'-trihydroxystilbene, and 3,4-dihydroxy-, 3,4,4'=trihydroxy-, and 3,4,3',4'-tetrahydroxybibenzyl. Oxidative cleavage of trans-stilbene to benzoic acid and 4-hydroxy- and 3,4-dihydroxybenzoic acid was established by the presence of both the free acids and conjugates of these compounds in both rabbit and rat urine. Their glycine conjugates were identified by thin-layer chromatography and quantitated by reverse isotope dilution procedures from unhydrolyzed rabbit and rat urine. Percentages obtained indicate that cleavage of trans-stilbene is more extensive in rabbits (9.5%) than in rats (2.7%)."}
{"id": "PMID:5267", "title": "Differential dependence on NADPH concentrations of two microsomal corticosteroid 21-hydroxylation reactions.", "content": "The dependency on NADPH concentrations of the bovine adrenal cortex microsomal 21-hydroxylation of progesterone and of 17-hydroxyprogesterone was investigated. The average Km for NADPH in the 21-hydroxylation of progesterone is 10.4 muM while that for the 21-hydroxylation of 17-hydroxyprogesterone is 0.6 muM. The optimal NADPH concentrations for these two hydroxylations are, in average, one order of magnitude apart. The different affinities of the two 21-hydroxylating activities with respect to NADPH may indicate the presence of independent 21-hydroxylation reactions for these two steroid substrates. This evidence is consistent with the observed genetic data in human congenital adrenal hyperplasia.", "contents": "Differential dependence on NADPH concentrations of two microsomal corticosteroid 21-hydroxylation reactions. The dependency on NADPH concentrations of the bovine adrenal cortex microsomal 21-hydroxylation of progesterone and of 17-hydroxyprogesterone was investigated. The average Km for NADPH in the 21-hydroxylation of progesterone is 10.4 muM while that for the 21-hydroxylation of 17-hydroxyprogesterone is 0.6 muM. The optimal NADPH concentrations for these two hydroxylations are, in average, one order of magnitude apart. The different affinities of the two 21-hydroxylating activities with respect to NADPH may indicate the presence of independent 21-hydroxylation reactions for these two steroid substrates. This evidence is consistent with the observed genetic data in human congenital adrenal hyperplasia."}
{"id": "PMID:5262", "title": "Identification of the urinary metabolites of 14C-bumetanide in the rat and their excretion by rats and dogs.", "content": "Unchanged bumetanide, 3-(n-butylamino)-4-phenoxy-5-sulfamoylbenzoic acid, and five metabolites were excreted in the urine of rats given 50 mg of 14C-labeled drug per kg intravenously. The metabolites, which were identified by mass spectrometry and/or nuclear magnetic resonance spectroscopy, arose by metabolic alteration of the n-butyl sidechain. In metabolites I-V, the butylamino group was converted to -NHCH2CH2CH2COOH, -NHCH2CH2CH2CH2OH,, -NHCH2CH2CHOHCH3, -NHCH2CH2CHOHCH2OH and -NH2, respectively. The total urinary and fecal excretion of labeled drug and metabolites after iv and oral administration of 14C-bumetanide was estimated in dogs given 0.5 mg/kg and in rats given 5 mg/kg. In the dog, the primary excretion product was unchanged drug, although evidence was obtained that the acyl glucuronide of bumetanide was secreted in dog bile. The major metabolite excreted by the rat was I, and negligible quantities of intact drug were excreted in the urine after oral or iv administration. Optical activity was found for the two metabolites that contained a chiral center (III and IV), indicating that they were formed by a stereoselective hydroxylation.", "contents": "Identification of the urinary metabolites of 14C-bumetanide in the rat and their excretion by rats and dogs. Unchanged bumetanide, 3-(n-butylamino)-4-phenoxy-5-sulfamoylbenzoic acid, and five metabolites were excreted in the urine of rats given 50 mg of 14C-labeled drug per kg intravenously. The metabolites, which were identified by mass spectrometry and/or nuclear magnetic resonance spectroscopy, arose by metabolic alteration of the n-butyl sidechain. In metabolites I-V, the butylamino group was converted to -NHCH2CH2CH2COOH, -NHCH2CH2CH2CH2OH,, -NHCH2CH2CHOHCH3, -NHCH2CH2CHOHCH2OH and -NH2, respectively. The total urinary and fecal excretion of labeled drug and metabolites after iv and oral administration of 14C-bumetanide was estimated in dogs given 0.5 mg/kg and in rats given 5 mg/kg. In the dog, the primary excretion product was unchanged drug, although evidence was obtained that the acyl glucuronide of bumetanide was secreted in dog bile. The major metabolite excreted by the rat was I, and negligible quantities of intact drug were excreted in the urine after oral or iv administration. Optical activity was found for the two metabolites that contained a chiral center (III and IV), indicating that they were formed by a stereoselective hydroxylation."}
{"id": "PMID:5264", "title": "Studies of the metabolism of parathion with an apparently homogeneous preparation of rabbit liver cytochrome P-450.", "content": "The metabolism of parathion has been examined by use of a reconstituted mixed-function oxidase enzyme system isolated from the livers of phenobarbital-pretreated rabbits. The cytochrome P-450 used in these studies was apparently homogeneous as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by assay of the preparation for contaminating microsomal enzymes and enzyme activity. These studies revealed that the apparently homogeneous preparation of cytochrome P-450, in the presence of the appropriate cofactors, can catalyze the conversions of parathion to both paraoxon and diethyl phosphorothioic acid. The present studies have also shown that parathion is metabolized by the reconstituted mixed-function oxidase enzyme system to diethyl phosphoric acid, a product which, in previous studies with intact liver microsomes, had been thought to arise exclusively from the hydrolysis of paraoxon by a microsomal esterase(s). The available data suggest that all three of the products of the metabolism of parathion by the reconstituted mixed-function oxidase enzyme system, namely, paraoxon, diethyl phosphorothioic acid, and diethyl phosphoric acid, are formed nonenzymatically by breakdown by different pathways of a common enzymatically formed intermediate. This common intermediate is thought to be the sulfine derivative of parathion formed in the mixed-function oxidase-catalyzed addition of an oxygen atom to one of the unshared electron pairs of the thiono-sulfur atom.", "contents": "Studies of the metabolism of parathion with an apparently homogeneous preparation of rabbit liver cytochrome P-450. The metabolism of parathion has been examined by use of a reconstituted mixed-function oxidase enzyme system isolated from the livers of phenobarbital-pretreated rabbits. The cytochrome P-450 used in these studies was apparently homogeneous as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by assay of the preparation for contaminating microsomal enzymes and enzyme activity. These studies revealed that the apparently homogeneous preparation of cytochrome P-450, in the presence of the appropriate cofactors, can catalyze the conversions of parathion to both paraoxon and diethyl phosphorothioic acid. The present studies have also shown that parathion is metabolized by the reconstituted mixed-function oxidase enzyme system to diethyl phosphoric acid, a product which, in previous studies with intact liver microsomes, had been thought to arise exclusively from the hydrolysis of paraoxon by a microsomal esterase(s). The available data suggest that all three of the products of the metabolism of parathion by the reconstituted mixed-function oxidase enzyme system, namely, paraoxon, diethyl phosphorothioic acid, and diethyl phosphoric acid, are formed nonenzymatically by breakdown by different pathways of a common enzymatically formed intermediate. This common intermediate is thought to be the sulfine derivative of parathion formed in the mixed-function oxidase-catalyzed addition of an oxygen atom to one of the unshared electron pairs of the thiono-sulfur atom."}
{"id": "PMID:5265", "title": "Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. IX. The formation of a 455-nm metabolite-cytochrome P-450 complex.", "content": "The reconstituted liver microsomal hydroxylation system was used to study the formation of a metabolite-cytochrome P-450 complex absorbing maximally at 455 nm, with benzphetamine and N-hydroxyamphetamine as substrates. Complex formation required the presence of NADPH, substrate, NADPH-cytochrome c reductase, lipid, and cytochrome P-450, indicating that metabolism of the substrate is essential. In the presence of fixed amounts of lipid and NADPH-cytochrome c reductase, the rate of complex formation with cytochrome P-450 isolated from phenobarbital-treated rats was much greater than that observed with cytochrome P-48 from 3-methylcholanthrene-treated rats or rabbits. These results are consistent with recent studies indicating that different forms of cytochrome P-450 with distinct spectral, catalytic, and immunological properties exist in liver microsomes.", "contents": "Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. IX. The formation of a 455-nm metabolite-cytochrome P-450 complex. The reconstituted liver microsomal hydroxylation system was used to study the formation of a metabolite-cytochrome P-450 complex absorbing maximally at 455 nm, with benzphetamine and N-hydroxyamphetamine as substrates. Complex formation required the presence of NADPH, substrate, NADPH-cytochrome c reductase, lipid, and cytochrome P-450, indicating that metabolism of the substrate is essential. In the presence of fixed amounts of lipid and NADPH-cytochrome c reductase, the rate of complex formation with cytochrome P-450 isolated from phenobarbital-treated rats was much greater than that observed with cytochrome P-48 from 3-methylcholanthrene-treated rats or rabbits. These results are consistent with recent studies indicating that different forms of cytochrome P-450 with distinct spectral, catalytic, and immunological properties exist in liver microsomes."}
{"id": "PMID:5279", "title": "The response of Ca-mediated action potentials and contractile activity in mammalian ventricular myocardium towards alkalosis.", "content": "Alkalosis (pH 7.8) produced by reduction of CO2 concentration augmented both upstroke velocity of Ca action potentials and isometric contractile force of mammalian heart muscle. If the increase of pH to 7.8 was achieved by a raise of HCO3 concentration (with simultaneous reduction of CO2 concentration), the positive inotropic response was not accompanied by an augmented Ca current. Obviously, the well-known positive inotropic effect of alkalosis does not only depend upon the enhancement of transmembrane Ca influx during excitation, but can be mediated alone by affecting intracellular Ca movements as well.", "contents": "The response of Ca-mediated action potentials and contractile activity in mammalian ventricular myocardium towards alkalosis. Alkalosis (pH 7.8) produced by reduction of CO2 concentration augmented both upstroke velocity of Ca action potentials and isometric contractile force of mammalian heart muscle. If the increase of pH to 7.8 was achieved by a raise of HCO3 concentration (with simultaneous reduction of CO2 concentration), the positive inotropic response was not accompanied by an augmented Ca current. Obviously, the well-known positive inotropic effect of alkalosis does not only depend upon the enhancement of transmembrane Ca influx during excitation, but can be mediated alone by affecting intracellular Ca movements as well."}
{"id": "PMID:5282", "title": "The in vitro effect of adrenergic agents and related compounds on triglyceride levels of guinea-pig lymphoid cells.", "content": "Isoproterenol, epinephrine and norepinephrine were highly potent in decreasing the triglyceride levels of the splenic lymphoid cells from guinea-pigs in vitro, while they were quite inert upon the inguinal lymph node cells.", "contents": "The in vitro effect of adrenergic agents and related compounds on triglyceride levels of guinea-pig lymphoid cells. Isoproterenol, epinephrine and norepinephrine were highly potent in decreasing the triglyceride levels of the splenic lymphoid cells from guinea-pigs in vitro, while they were quite inert upon the inguinal lymph node cells."}
{"id": "PMID:5283", "title": "Assimilation of ammonia and growth of biotin deficient Aspergillus nidulans.", "content": "Biotin deficiency in Aspergillus nidulans has been found to increase the uptake of ammonium ions, associated with a marked increase in the activity of NADP-linked glutamate dehydrogenase, which is found to be the major route of ammonia assimilation in this culture. The results obtained are discussed with respect to the growth of Aspergillus nidulans during biotin deficiency.", "contents": "Assimilation of ammonia and growth of biotin deficient Aspergillus nidulans. Biotin deficiency in Aspergillus nidulans has been found to increase the uptake of ammonium ions, associated with a marked increase in the activity of NADP-linked glutamate dehydrogenase, which is found to be the major route of ammonia assimilation in this culture. The results obtained are discussed with respect to the growth of Aspergillus nidulans during biotin deficiency."}
{"id": "PMID:5284", "title": "[Differential properties of two molecular forms of 4-aminobutyrate-2-ketoglutarate transaminase (GABAT) from pig brain (author's transl)].", "content": "The two forms isolated exhibit some differences concerning their physicochemical and functional properties. They are identical with the previously purified molecular fomrs, GABAT I and GABAT II, separated by DEAE cellulose chromatography.", "contents": "[Differential properties of two molecular forms of 4-aminobutyrate-2-ketoglutarate transaminase (GABAT) from pig brain (author's transl)]. The two forms isolated exhibit some differences concerning their physicochemical and functional properties. They are identical with the previously purified molecular fomrs, GABAT I and GABAT II, separated by DEAE cellulose chromatography."}
{"id": "PMID:5285", "title": "Acrosomal hydrolases in buffalo spermatozoa.", "content": "Buffalo sperm acrosome resembles its counterpart in other species, being rich in hydrolytic enzymes. Of the enzyme activities estimated, acid phosphatase, beta-N-acetylglucosaminidase and hyaluronidase were low compared to those of ram semen. However, the aryl sulphatase activity was high. GOT activity estimated in sperm preparation may not be of acrosomal origin.", "contents": "Acrosomal hydrolases in buffalo spermatozoa. Buffalo sperm acrosome resembles its counterpart in other species, being rich in hydrolytic enzymes. Of the enzyme activities estimated, acid phosphatase, beta-N-acetylglucosaminidase and hyaluronidase were low compared to those of ram semen. However, the aryl sulphatase activity was high. GOT activity estimated in sperm preparation may not be of acrosomal origin."}
{"id": "PMID:5286", "title": "Ecdysome 20-hydroxylase from the midgut of the tobacco hornworm (Manduca sexta L.).", "content": "An ecdysone 20-hydroxylase enzyme system that converts alpha-ecdysone to 20-hydroxyecdysone was prepared from the midgut of the tobacco hornworm prepupa. This partially purified enzyme is NADPH dependent and is localized in the mitochondrial fraction of the midgut tissue.", "contents": "Ecdysome 20-hydroxylase from the midgut of the tobacco hornworm (Manduca sexta L.). An ecdysone 20-hydroxylase enzyme system that converts alpha-ecdysone to 20-hydroxyecdysone was prepared from the midgut of the tobacco hornworm prepupa. This partially purified enzyme is NADPH dependent and is localized in the mitochondrial fraction of the midgut tissue."}
{"id": "PMID:5287", "title": "On the regulatory properties of a halophilic malic enzyme from Halobacterium cutirubrum.", "content": "The NADP-linked malic enzyme from Halobacterium cutirubrum is strongly inhibited by acetyl-CoA and NADH, and rather weakly inhibited by oxaloacetate and glyoxylate, in the presence of very high KCl concentrations (3 M), considered physiological for the extremely halophilic bacteria.", "contents": "On the regulatory properties of a halophilic malic enzyme from Halobacterium cutirubrum. The NADP-linked malic enzyme from Halobacterium cutirubrum is strongly inhibited by acetyl-CoA and NADH, and rather weakly inhibited by oxaloacetate and glyoxylate, in the presence of very high KCl concentrations (3 M), considered physiological for the extremely halophilic bacteria."}
{"id": "PMID:5288", "title": "Fermentative digestion of food in the colobus monkey, Colobus, polykomos.", "content": "Fermentation of leafy food occurs in the enlarged saccus gastricus of the colobus monkey with the formation of volatile fatty acid, as in the rumen of ruminant animals. About half of the digestible organic matter and cellulose of the diet is digested in this way.", "contents": "Fermentative digestion of food in the colobus monkey, Colobus, polykomos. Fermentation of leafy food occurs in the enlarged saccus gastricus of the colobus monkey with the formation of volatile fatty acid, as in the rumen of ruminant animals. About half of the digestible organic matter and cellulose of the diet is digested in this way."}
{"id": "PMID:5303", "title": "Isolation, purification and properties of aortic elastase.", "content": "An elastase from pig aorta has been partially purified and characterised; it exhibits immunological cross reaction with pig pancreatic elastase. Its proteolytic (k-elastin gel and polymeric elastin substrates) and esterolytic (N-succinoyl-trialanine paranitroanilide) activities as well as its degree of inhibition by serum protease inhibitors (alpha1-antitrypsin and alpha2-macro-globulin) differ sensibly from those of pancreatic elastase [14,16].", "contents": "Isolation, purification and properties of aortic elastase. An elastase from pig aorta has been partially purified and characterised; it exhibits immunological cross reaction with pig pancreatic elastase. Its proteolytic (k-elastin gel and polymeric elastin substrates) and esterolytic (N-succinoyl-trialanine paranitroanilide) activities as well as its degree of inhibition by serum protease inhibitors (alpha1-antitrypsin and alpha2-macro-globulin) differ sensibly from those of pancreatic elastase [14,16]."}
{"id": "PMID:5312", "title": "Some chemical aspects of histamine H2-receptor antagonists.", "content": "Certain chemical properties, which may determine the biological actions of the recently discovered histamine H2-receptor antagonists burimamide and metiamide, are identified, partly by considering the derivation of these antagonists. Examples are given of attempts to design antagonists using histamine as starting point. A partial agonist was eventually obtained through modifying the side chain of histamine but retaining the imidazole ring. Further developments led to the synthesis of uncharged thioureido analogues and to the discovery of the antagonist, burimamide. Consideration of the relative concentration of imidazole tautomers led to the replacement of a methylene group (-CH2-) with an isosteric thioether (-S-) link in the side chain, and incorporation of a methyl group in the imidazole ring; these changes afforded metiamide, an orally active antagonist. These developments emphasize that the imidazole ring appears to have a special importance at H2 receptors. Burimamide and metiamide are hydrophilic molecules that resemble histamine in having an imidazole ring but differ in the side chain which, though polar, is uncharged. By contrast, the H1-receptor antihistaminic drugs are lipophilic molecules; their resemblance to histamine is in having a positively charged ammonium side chain. These substantial chemical differences between the respective antagonists probably determine their selectivity in distinguishing between the two types of histamine receptor. Furthermore, the very low lipophilicities of these H2-receptor antagonists probably account for the lack of central nervous system and local anesthetic effects normally associated with the use of antihistaminic drugs.", "contents": "Some chemical aspects of histamine H2-receptor antagonists. Certain chemical properties, which may determine the biological actions of the recently discovered histamine H2-receptor antagonists burimamide and metiamide, are identified, partly by considering the derivation of these antagonists. Examples are given of attempts to design antagonists using histamine as starting point. A partial agonist was eventually obtained through modifying the side chain of histamine but retaining the imidazole ring. Further developments led to the synthesis of uncharged thioureido analogues and to the discovery of the antagonist, burimamide. Consideration of the relative concentration of imidazole tautomers led to the replacement of a methylene group (-CH2-) with an isosteric thioether (-S-) link in the side chain, and incorporation of a methyl group in the imidazole ring; these changes afforded metiamide, an orally active antagonist. These developments emphasize that the imidazole ring appears to have a special importance at H2 receptors. Burimamide and metiamide are hydrophilic molecules that resemble histamine in having an imidazole ring but differ in the side chain which, though polar, is uncharged. By contrast, the H1-receptor antihistaminic drugs are lipophilic molecules; their resemblance to histamine is in having a positively charged ammonium side chain. These substantial chemical differences between the respective antagonists probably determine their selectivity in distinguishing between the two types of histamine receptor. Furthermore, the very low lipophilicities of these H2-receptor antagonists probably account for the lack of central nervous system and local anesthetic effects normally associated with the use of antihistaminic drugs."}
{"id": "PMID:5313", "title": "The pharmacology of burimamide and metiamide, two histamine H2-receptor antagonists.", "content": "Burimamide and metiamide are two histamine H2-receptor antagonists. Evidence is presented that indicates the competitive nature and the specificity of the antagonism. Metiamide is about ten times more potent than burimamide and is also more effective than burimamide when given orally. Both compounds inhibit gastric secretion and the evidence is consistent with this inhibition being due to competitive antagonism of H2 receptors in the gastric mucosa. Burimamide, unlike metiamide, causes release of catecholamines even at dose levels that are just sufficient to produce H2-receptor antagonism. Burimamide, but not metiamide, has alpha-adrenoceptor blocking activity. In certain models for inflammation, particularly rat paw edema induced by compound 48/80, burimamide in combination with the H1-receptor antagonist mepyramine shows anti-inflammatory activity. This may, in part, be associated with the catecholamine-releasing properties of the compound. Metiamide is less active in this respect.", "contents": "The pharmacology of burimamide and metiamide, two histamine H2-receptor antagonists. Burimamide and metiamide are two histamine H2-receptor antagonists. Evidence is presented that indicates the competitive nature and the specificity of the antagonism. Metiamide is about ten times more potent than burimamide and is also more effective than burimamide when given orally. Both compounds inhibit gastric secretion and the evidence is consistent with this inhibition being due to competitive antagonism of H2 receptors in the gastric mucosa. Burimamide, unlike metiamide, causes release of catecholamines even at dose levels that are just sufficient to produce H2-receptor antagonism. Burimamide, but not metiamide, has alpha-adrenoceptor blocking activity. In certain models for inflammation, particularly rat paw edema induced by compound 48/80, burimamide in combination with the H1-receptor antagonist mepyramine shows anti-inflammatory activity. This may, in part, be associated with the catecholamine-releasing properties of the compound. Metiamide is less active in this respect."}
{"id": "PMID:5314", "title": "Identification and blockade of vascular H2 receptors.", "content": "Experiments were conducted in anesthetized dogs to determine the nature of receptors mediating vascular actions of histamine. In the perfused gracilis muscle histamine caused vasodilatation that was attenuated in part by mepyramine, an H1-receptor blocker. Metiamide, an H2 blocker, given alone had no effect on dilatation. However, the combination of mepyramine and metiamide resulted in a large attenuation of dilatation. Histamine caused constriction of the perfused saphenous vein that was totally blocked by mepyramine suggesting that venoconstriction by histamine involves only H1 receptors. Histamine infusion caused a fall in arterial pressure and a large reduction in peripheral resistance. Mepyramine attenuated the fall in pressure but not the reduction in resistance. Combined H1- and H2-receptor blockade largely eliminated the effects of histamine infusion further documenting the existence of H1 and H2 receptors. The effects of H1 and H2 antihistamines on a variety of physiological vasodilator responses were examined. Evidence was obtained to indicate that H1- and H2-histamine receptors are involved in the active component of baroreceptor-mediated reflex vasodilatation, poststimulation vasodilatation, sympathetic vasodilatation in the guanethidine-treated dog, and vasodilator responses following compound 48/80. No evidence for the participation of either H1- or H2-histamine receptors in reactive hyperemia or the dilatation accompanying exercise was found. It is concluded that in the dog both endogenously-released and exogenous histamine exert vascular effects by activation of both H1 and H2 receptors.", "contents": "Identification and blockade of vascular H2 receptors. Experiments were conducted in anesthetized dogs to determine the nature of receptors mediating vascular actions of histamine. In the perfused gracilis muscle histamine caused vasodilatation that was attenuated in part by mepyramine, an H1-receptor blocker. Metiamide, an H2 blocker, given alone had no effect on dilatation. However, the combination of mepyramine and metiamide resulted in a large attenuation of dilatation. Histamine caused constriction of the perfused saphenous vein that was totally blocked by mepyramine suggesting that venoconstriction by histamine involves only H1 receptors. Histamine infusion caused a fall in arterial pressure and a large reduction in peripheral resistance. Mepyramine attenuated the fall in pressure but not the reduction in resistance. Combined H1- and H2-receptor blockade largely eliminated the effects of histamine infusion further documenting the existence of H1 and H2 receptors. The effects of H1 and H2 antihistamines on a variety of physiological vasodilator responses were examined. Evidence was obtained to indicate that H1- and H2-histamine receptors are involved in the active component of baroreceptor-mediated reflex vasodilatation, poststimulation vasodilatation, sympathetic vasodilatation in the guanethidine-treated dog, and vasodilator responses following compound 48/80. No evidence for the participation of either H1- or H2-histamine receptors in reactive hyperemia or the dilatation accompanying exercise was found. It is concluded that in the dog both endogenously-released and exogenous histamine exert vascular effects by activation of both H1 and H2 receptors."}
{"id": "PMID:5315", "title": "Cardiac histamine receptors.", "content": "Current evidence pertinent to the identification of cardiac histamine receptors in the guinea pig is reviewed. Pharmacological characterization has been aided by the use of selective agonists and antagonists for both types of histamine receptors. It appears that both H1 and H2 receptors mediate the cardiac effects of histamine. Histamine H2 receptors mediate the positive chronotropic and ventricular inotropic effects. H1 receptors mediate the negative dromotropic effect of histamine and possibly the atrial inotropic effect. Histamine-induced arrhythmias involve H1 receptors (arrhythmias of conduction) or H2 receptors (arrhythmias of automaticity), or both. The receptors mediating the histamine-induced increase in coronary flow are not as clearly defined: both H1 and H2 receptors might be implicated.", "contents": "Cardiac histamine receptors. Current evidence pertinent to the identification of cardiac histamine receptors in the guinea pig is reviewed. Pharmacological characterization has been aided by the use of selective agonists and antagonists for both types of histamine receptors. It appears that both H1 and H2 receptors mediate the cardiac effects of histamine. Histamine H2 receptors mediate the positive chronotropic and ventricular inotropic effects. H1 receptors mediate the negative dromotropic effect of histamine and possibly the atrial inotropic effect. Histamine-induced arrhythmias involve H1 receptors (arrhythmias of conduction) or H2 receptors (arrhythmias of automaticity), or both. The receptors mediating the histamine-induced increase in coronary flow are not as clearly defined: both H1 and H2 receptors might be implicated."}
{"id": "PMID:5322", "title": "Lack of relationship between cyclic nucleotide levels and spermatozoal function in human semen.", "content": "Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were determined in 103 samples of human semen and grouped according to the number of spermatozoa in the ejaculate. No correlation was found between cyclic AMP concentrations and the number, motility, and morphology of the spermatozoa or the fructose content, pH, and volume of the ejaculate. Similar findings were obtained with cyclic guanosine 3':5'-monophosphate levels in 24 samples of human semen. Therefore, cyclic nucleotide levels in human semen appear to be derived from sources other than spermatozoal adenylyl or guanylyl cyclase.", "contents": "Lack of relationship between cyclic nucleotide levels and spermatozoal function in human semen. Cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were determined in 103 samples of human semen and grouped according to the number of spermatozoa in the ejaculate. No correlation was found between cyclic AMP concentrations and the number, motility, and morphology of the spermatozoa or the fructose content, pH, and volume of the ejaculate. Similar findings were obtained with cyclic guanosine 3':5'-monophosphate levels in 24 samples of human semen. Therefore, cyclic nucleotide levels in human semen appear to be derived from sources other than spermatozoal adenylyl or guanylyl cyclase."}
{"id": "PMID:5325", "title": "Quality, efficiency, and cost of a physician-assistant-protocol system for managment of diabetes and hypertension.", "content": "Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The  care rendered by the protocol system was compared with care rendered by a \"traditional\" system in the same clinic in  which physicians delegated few clinical tasks. Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely.", "contents": "Quality, efficiency, and cost of a physician-assistant-protocol system for managment of diabetes and hypertension. Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The  care rendered by the protocol system was compared with care rendered by a \"traditional\" system in the same clinic in  which physicians delegated few clinical tasks. Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely."}
{"id": "PMID:5326", "title": "Suppression and stimulation mechanisms controlling glucagon secretion in a case of islet-cell tumor producing glucagon, insulin, and gastrin.", "content": "The mechanisms controlling secretion of glucagon and other pancreatic hormones were studied in a patient affected with multihormone-secreting islet-cell tumor. Fasting glucagon levels (3,000 pg./ml.) rose to 10 ng./ml. following arginine stimulation. While oral glucose load and intravenous glucose infusion did not suppress glucagon secretion, insulin administration induced a prompt depression in glucagon levels. Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase. It is suggested that only some of the stimulation-inhibition mechanisms were conserved in this case of glucagon-secreting pancreatic tumor.", "contents": "Suppression and stimulation mechanisms controlling glucagon secretion in a case of islet-cell tumor producing glucagon, insulin, and gastrin. The mechanisms controlling secretion of glucagon and other pancreatic hormones were studied in a patient affected with multihormone-secreting islet-cell tumor. Fasting glucagon levels (3,000 pg./ml.) rose to 10 ng./ml. following arginine stimulation. While oral glucose load and intravenous glucose infusion did not suppress glucagon secretion, insulin administration induced a prompt depression in glucagon levels. Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase. It is suggested that only some of the stimulation-inhibition mechanisms were conserved in this case of glucagon-secreting pancreatic tumor."}
{"id": "PMID:5335", "title": "Histamine effects on H+ permeability by isolated gastric mucosa.", "content": "This study examines the effects of histamine on mucosal permeability to acid by isolated stomach of rabbits. Histamine (9 X 10(-5) M) decreased antral luminal acid loss which could not be accounted for by active H+ secretion or appearance of organic acid. Histamine also increased antral electrical resistance and decreased the unidirectional luminal to serosal flux (Jls) of (14)c-erythritol. Histamine, theophylline, and N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate did not significantly alter secretion by fundus in the presence of salicylate (5 X 10(-3)M). However, after removal of salicylate, these agents stimulated acid secretion. Histamine decreased luminal acid loss by both antrum and fundus treated with salicylate, increased the electrical resistance of these tissues, and decreased Jls erythritol of fundic mucosa. Burimamide (1 X 10(-3) M) inhibited the permeability effects of histamine on antrum and fundus. The data indicate that histamine decreases spontaneous antral mucosal permeability as well as salicylate-induced increase in mucosal permeability of both antrum and fundus. The effects of burimamide suggest that antrum contains H2 receptor sites urelated to acid secretion and that fundus contains H2 receptor sites which also govern permeability but are independent of those related to acid secretion.", "contents": "Histamine effects on H+ permeability by isolated gastric mucosa. This study examines the effects of histamine on mucosal permeability to acid by isolated stomach of rabbits. Histamine (9 X 10(-5) M) decreased antral luminal acid loss which could not be accounted for by active H+ secretion or appearance of organic acid. Histamine also increased antral electrical resistance and decreased the unidirectional luminal to serosal flux (Jls) of (14)c-erythritol. Histamine, theophylline, and N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate did not significantly alter secretion by fundus in the presence of salicylate (5 X 10(-3)M). However, after removal of salicylate, these agents stimulated acid secretion. Histamine decreased luminal acid loss by both antrum and fundus treated with salicylate, increased the electrical resistance of these tissues, and decreased Jls erythritol of fundic mucosa. Burimamide (1 X 10(-3) M) inhibited the permeability effects of histamine on antrum and fundus. The data indicate that histamine decreases spontaneous antral mucosal permeability as well as salicylate-induced increase in mucosal permeability of both antrum and fundus. The effects of burimamide suggest that antrum contains H2 receptor sites urelated to acid secretion and that fundus contains H2 receptor sites which also govern permeability but are independent of those related to acid secretion."}
{"id": "PMID:5336", "title": "Genetics of murine liver and kidney arysulfatase b.", "content": "Mice from 12 inbred strains were surveyed for variation of kidney and liver arylsulfatase levels. Kidney variation was due to differences in the activity of arylsulfatase B. Twofold higher activities of arylsulfatase B in SWR/J kidney compared to A/HeJ kidney were determined by an autosomal gene which may be identical to the structural gene for arylsulfatase B since the SWR/J enzyme was more heat-stable than the A/HeJ enzyme. C57BL/6J mice possessed two-fold higher liver arylsulfatase levels than did A/HeJ mice. The major portion of this variation could be attributed to differences in arylsulfatase B, and appeared to be inherited in autosomal fashion. Although some evidence supports the existence of a major locus influencing liver arylsulfatase activity, this must be substantiated by further studies. Whatever the nature of the genetic factors involved, they do not appear to involve structural genes since no differences were discernible between the enzymes of the two strains relevant to Km, heat stability, electrophoretic mobility, pH optimum, activation energy, or response to several inhibitors. Furthermore, the rank ordering of strains on the basis of kidney arylsulfatase activity differed markedly from that which pertained to liver activity. Kidney arylsulfatase levels, but not brain or liver arylsulfatase activities, appear subject to androgenic influences.", "contents": "Genetics of murine liver and kidney arysulfatase b. Mice from 12 inbred strains were surveyed for variation of kidney and liver arylsulfatase levels. Kidney variation was due to differences in the activity of arylsulfatase B. Twofold higher activities of arylsulfatase B in SWR/J kidney compared to A/HeJ kidney were determined by an autosomal gene which may be identical to the structural gene for arylsulfatase B since the SWR/J enzyme was more heat-stable than the A/HeJ enzyme. C57BL/6J mice possessed two-fold higher liver arylsulfatase levels than did A/HeJ mice. The major portion of this variation could be attributed to differences in arylsulfatase B, and appeared to be inherited in autosomal fashion. Although some evidence supports the existence of a major locus influencing liver arylsulfatase activity, this must be substantiated by further studies. Whatever the nature of the genetic factors involved, they do not appear to involve structural genes since no differences were discernible between the enzymes of the two strains relevant to Km, heat stability, electrophoretic mobility, pH optimum, activation energy, or response to several inhibitors. Furthermore, the rank ordering of strains on the basis of kidney arylsulfatase activity differed markedly from that which pertained to liver activity. Kidney arylsulfatase levels, but not brain or liver arylsulfatase activities, appear subject to androgenic influences."}
{"id": "PMID:5338", "title": "[A study of H-2 mutations in mice. V. Detection of mutations M505, Hzl and M506 in the host vs transplant reaction].", "content": "H-2 mutant/normal pairs of congenic mouse strains C57BL/6equilibriumB6.M505 (H-2Kbd), C57BL/6equilibriumB6.C(Hz1) (H-2Kba) and A.CAequilibriumA.CA(M506) (H-2fa) were studied in the graft versus host assay. All the three mutations were expressed in these tests as gain and loss of H-2 antigen. The data obtained confirm an earlier suggestion that the H-2K antigenic molecule bears antigenic determinants which could be detected by a variety of immunological techniques.", "contents": "[A study of H-2 mutations in mice. V. Detection of mutations M505, Hzl and M506 in the host vs transplant reaction]. H-2 mutant/normal pairs of congenic mouse strains C57BL/6equilibriumB6.M505 (H-2Kbd), C57BL/6equilibriumB6.C(Hz1) (H-2Kba) and A.CAequilibriumA.CA(M506) (H-2fa) were studied in the graft versus host assay. All the three mutations were expressed in these tests as gain and loss of H-2 antigen. The data obtained confirm an earlier suggestion that the H-2K antigenic molecule bears antigenic determinants which could be detected by a variety of immunological techniques."}
{"id": "PMID:5339", "title": "[Description of new mutant forms of erythrocyte glucose-6-phosphate dehydrogenase in man].", "content": "9 variants of human erythrocyte glucose-6-phosphate dehydrogenase (G6PD) were isolated from erythrocytes of patients with G6PD deficiency and partially purified according to WHO program for stanartization of methods for studying G6PD. The results of physico-chemical study of these enzymes (determination of electrophoretic mobility, kappaM for G6P and NADP, pH optimum and thermostability) permit tu consider 5 of them to be new mutations of G6PD previously not described in literature. The observed high geterogeneity of variants of G6PD in Azerbaijan is discussed.", "contents": "[Description of new mutant forms of erythrocyte glucose-6-phosphate dehydrogenase in man]. 9 variants of human erythrocyte glucose-6-phosphate dehydrogenase (G6PD) were isolated from erythrocytes of patients with G6PD deficiency and partially purified according to WHO program for stanartization of methods for studying G6PD. The results of physico-chemical study of these enzymes (determination of electrophoretic mobility, kappaM for G6P and NADP, pH optimum and thermostability) permit tu consider 5 of them to be new mutations of G6PD previously not described in literature. The observed high geterogeneity of variants of G6PD in Azerbaijan is discussed."}
{"id": "PMID:5340", "title": "[The interrelationship between the inhibitory activity of milk with different types of beta-lactoglobulins and the resistance of cattle to mastitis].", "content": "In the course of the investigation of piebald (black-white) cattle it is found that 17,62% animals produce the AA type beta-lactoglobulin, 49,52%--the AB type and 32,86%--the BB type. The higher inhibitory activity of milk with the BB type beta-lactoglobulin was found which retained in dilution 1 : 32. The total flora of teat, cyst and parenchyma milk of animals with the BB type beta-lactoglobulin as well as Enterococcus bacteria were much lower than in milk of cows with the AA type homogenous form. The animals with the first type of milk protein had mastitis more rarely as compared to those with the second type. The animals with heterogenous form of beta-lactoglobulin had intermediate values in most of their characteristics.", "contents": "[The interrelationship between the inhibitory activity of milk with different types of beta-lactoglobulins and the resistance of cattle to mastitis]. In the course of the investigation of piebald (black-white) cattle it is found that 17,62% animals produce the AA type beta-lactoglobulin, 49,52%--the AB type and 32,86%--the BB type. The higher inhibitory activity of milk with the BB type beta-lactoglobulin was found which retained in dilution 1 : 32. The total flora of teat, cyst and parenchyma milk of animals with the BB type beta-lactoglobulin as well as Enterococcus bacteria were much lower than in milk of cows with the AA type homogenous form. The animals with the first type of milk protein had mastitis more rarely as compared to those with the second type. The animals with heterogenous form of beta-lactoglobulin had intermediate values in most of their characteristics."}
{"id": "PMID:5341", "title": "[Genetic control of allogenic inhibition of hematopoietic stem cells].", "content": "Adult mice of C57BL/6, CBA (CBA X C57BL/6) F1, (CBA X C57BL/6) F2, F1 X CBA and F1 X C57BL/6 strains were lethally irradiated and reconstituted with a constant dose of 3-10(5) C57BL/6 bone marrow cells. At the 9th day after the bone marrow transplantation the colony count was performed in spleen of irradiated recipients. In the spleen of F1, CBA and C57BL/6 mice were registered low (0--8, intermediate (6--18) and high (22-40) numbers of colonies respectively. The segregation ratios in F2 progeny were close to 2 (low): 1(intermediate): 1(high). The segregation ratios in backcross (F1 X CBA) were close to 1(low): 1(intermediate)numbers of colonies. Backcrosses (F1 X C57BL/6) were distributed to low and high numbers of colonies with the ratio 1:1. The number of spleen colonies of males and females was the same in all segregating progeny. The results of hybrid analysis suggest that a single pair of allelic genes is involved in genetic control of allogenic inhibition, and that the resistance (manifestation of inhibition) to C57BL/6 stem cells is conferred by the dominant allele.", "contents": "[Genetic control of allogenic inhibition of hematopoietic stem cells]. Adult mice of C57BL/6, CBA (CBA X C57BL/6) F1, (CBA X C57BL/6) F2, F1 X CBA and F1 X C57BL/6 strains were lethally irradiated and reconstituted with a constant dose of 3-10(5) C57BL/6 bone marrow cells. At the 9th day after the bone marrow transplantation the colony count was performed in spleen of irradiated recipients. In the spleen of F1, CBA and C57BL/6 mice were registered low (0--8, intermediate (6--18) and high (22-40) numbers of colonies respectively. The segregation ratios in F2 progeny were close to 2 (low): 1(intermediate): 1(high). The segregation ratios in backcross (F1 X CBA) were close to 1(low): 1(intermediate)numbers of colonies. Backcrosses (F1 X C57BL/6) were distributed to low and high numbers of colonies with the ratio 1:1. The number of spleen colonies of males and females was the same in all segregating progeny. The results of hybrid analysis suggest that a single pair of allelic genes is involved in genetic control of allogenic inhibition, and that the resistance (manifestation of inhibition) to C57BL/6 stem cells is conferred by the dominant allele."}
{"id": "PMID:5342", "title": "Inhibition of food-stimulated gastric acid secretion by cimetidine.", "content": "The effect of cimetidine, a new histamine H2-receptor antagonist, on gastric acid secretion stimulated by a homogenised meal was studied in six normal volunteers using an in vivo intragastric titration technique. The subjects were studied twice, no more than 48 h apart, receiving either cimetidine 200 mg or placebo in random order. Cimetidine administered either 32 men before (three subjects) or with the meal (three subjects) significantly inhibited gastric acid secretion in all the subjects throughout the period of study; 96 min after food, total acid secretion decreased by 67 and 57% respectively. When the drug was taken with the meal absorption was slower (mean peak blood level 2-34 mumol/l, 80-128 min after dosing) than when administered on an empty stomach (mean peak blood level 5-08 mumol/l, 48-64 min after dosing). Blood cimetidine concentration correlated significantly (P less than 0-01) with percentage inhibition of acid output and the calculated concentration resulting in 50% inhibition of gastric acid secretion (IC50) was 1-6 mumol/l. Secretion of gastrin in response to food was unaffected by cimetidine. The results suggest that 200 mg cimetidine effectively inhibits food-stimulated acid secretion and that the bioavailability of the drug may be affected by the timing of dosage in relation to meals. No unwanted effect were observed.", "contents": "Inhibition of food-stimulated gastric acid secretion by cimetidine. The effect of cimetidine, a new histamine H2-receptor antagonist, on gastric acid secretion stimulated by a homogenised meal was studied in six normal volunteers using an in vivo intragastric titration technique. The subjects were studied twice, no more than 48 h apart, receiving either cimetidine 200 mg or placebo in random order. Cimetidine administered either 32 men before (three subjects) or with the meal (three subjects) significantly inhibited gastric acid secretion in all the subjects throughout the period of study; 96 min after food, total acid secretion decreased by 67 and 57% respectively. When the drug was taken with the meal absorption was slower (mean peak blood level 2-34 mumol/l, 80-128 min after dosing) than when administered on an empty stomach (mean peak blood level 5-08 mumol/l, 48-64 min after dosing). Blood cimetidine concentration correlated significantly (P less than 0-01) with percentage inhibition of acid output and the calculated concentration resulting in 50% inhibition of gastric acid secretion (IC50) was 1-6 mumol/l. Secretion of gastrin in response to food was unaffected by cimetidine. The results suggest that 200 mg cimetidine effectively inhibits food-stimulated acid secretion and that the bioavailability of the drug may be affected by the timing of dosage in relation to meals. No unwanted effect were observed."}
{"id": "PMID:5346", "title": "[Morbus Crohn (enteritis regionalis)].", "content": "Crohn's disease (regional enteritis) is a chronic non-specific inflammatory intestinal disorder of unknown etiology. Most commonly the terminal ileum in involved, a segmentary involvement of the bowel wall is rather characteristic. Main symptoms are recurrent abdominal pain, fever, diarrhea and weight loss. Radiological and endoscopic examination confirms the diagnosis, granulomas in the biopsy specimen are pathognomonic. In differential diagnosis ulcerative and ischaemic colitis have to be ruled out. Conservative therapy with prednisolone and salazopyrin is the method of choice, however, complications like small bowel obstruction, toxic megacolon and fistulae ask for surgical intervention.", "contents": "[Morbus Crohn (enteritis regionalis)]. Crohn's disease (regional enteritis) is a chronic non-specific inflammatory intestinal disorder of unknown etiology. Most commonly the terminal ileum in involved, a segmentary involvement of the bowel wall is rather characteristic. Main symptoms are recurrent abdominal pain, fever, diarrhea and weight loss. Radiological and endoscopic examination confirms the diagnosis, granulomas in the biopsy specimen are pathognomonic. In differential diagnosis ulcerative and ischaemic colitis have to be ruled out. Conservative therapy with prednisolone and salazopyrin is the method of choice, however, complications like small bowel obstruction, toxic megacolon and fistulae ask for surgical intervention."}
{"id": "PMID:5347", "title": "[Levamisole, a chemically defined substance with immunostimulating potential--a review].", "content": "In contrast to immunosuppression, immunostimulation is still at an early stage of development. Levamisole is the first chemically defined substance with immunostimulating potential which can be applied systemically. After a short consideration of the chemistry and pharmacology of Levamisole, its effect in different animal experimental models of humoral and cell-mediated immunity are discussed in detail. Moreover, the following review deals with the influence of Levamisole on several immunological parameters in man. Finally, the therapeutical results achieved up to now by different clinical indications are reported.", "contents": "[Levamisole, a chemically defined substance with immunostimulating potential--a review]. In contrast to immunosuppression, immunostimulation is still at an early stage of development. Levamisole is the first chemically defined substance with immunostimulating potential which can be applied systemically. After a short consideration of the chemistry and pharmacology of Levamisole, its effect in different animal experimental models of humoral and cell-mediated immunity are discussed in detail. Moreover, the following review deals with the influence of Levamisole on several immunological parameters in man. Finally, the therapeutical results achieved up to now by different clinical indications are reported."}
{"id": "PMID:5345", "title": "Oral lesions caused by habits.", "content": "Oral lesions caused by habits can be of teeth only, of teeth and the soft tissues of the mouth or may be only of the soft tissues. Lesions of teeth are permanent and may remain even when there has been total destruction of soft tissues. Recognition of lesions due to habits such as betel chewing, snuff dipping, pipe smoking and certain sexual practices may help towards establishing the sex, the ethnic grouping or even the place of origin of a person or their remains. Certain dental and gingival changes may indicate a person's working circumstances and even the type of treatment received.", "contents": "Oral lesions caused by habits. Oral lesions caused by habits can be of teeth only, of teeth and the soft tissues of the mouth or may be only of the soft tissues. Lesions of teeth are permanent and may remain even when there has been total destruction of soft tissues. Recognition of lesions due to habits such as betel chewing, snuff dipping, pipe smoking and certain sexual practices may help towards establishing the sex, the ethnic grouping or even the place of origin of a person or their remains. Certain dental and gingival changes may indicate a person's working circumstances and even the type of treatment received."}
{"id": "PMID:5372", "title": "Adherence of bacterial to vaginal epithelial cells.", "content": "Vaginal epithelial cells from healthy women were washed and incubated in tissue culture medium with freshly isolated bacteria of the indigenous vaginal flora and with bacteria of species that have been discussed in conjunction with genital infections. After incubation and washing, the number of bacteria that adhered per cell was determined. The influence on the attachment rate of such factors as variations in the washing procedure, bacterial density, and incubation time was assessed. Lactobacillus acidophilus and other bacterial species that occur in the lower genital tract of healthy women, e.g., some strictly anaerobic species, adhered by significantly lower numbers per cell than Neisseria gonorrhoeae, group B streptococci, and Corynebacterium vaginale. Significantly more freshly isolated gonococci adhered per cell than gonococci that had been passaged on artificial medium. The adherence of gonococci increased with increasing acidity of the test medium.", "contents": "Adherence of bacterial to vaginal epithelial cells. Vaginal epithelial cells from healthy women were washed and incubated in tissue culture medium with freshly isolated bacteria of the indigenous vaginal flora and with bacteria of species that have been discussed in conjunction with genital infections. After incubation and washing, the number of bacteria that adhered per cell was determined. The influence on the attachment rate of such factors as variations in the washing procedure, bacterial density, and incubation time was assessed. Lactobacillus acidophilus and other bacterial species that occur in the lower genital tract of healthy women, e.g., some strictly anaerobic species, adhered by significantly lower numbers per cell than Neisseria gonorrhoeae, group B streptococci, and Corynebacterium vaginale. Significantly more freshly isolated gonococci adhered per cell than gonococci that had been passaged on artificial medium. The adherence of gonococci increased with increasing acidity of the test medium."}
{"id": "PMID:5373", "title": "Biological properties of an immunogenic pneumococcal subcellular preparation.", "content": "A subcellular fraction, designated PSP-3R, prepared from rough, type 3R Streptococcus pneumoniae is described, which affords excellent protection to mice against challenge with smooth organisms of the homologous serotype 3S and significant protection against heterologous challenge with serotypes 1S and 2S. Adjuvant enhances the protective capacity of the vaccine but is not necessary for immunogenicity. Protection induced by PSP-3R can be passively transferred tp normal mice with serum from actively immunized animals. The protective capacity can be completely absorbed out with rough or smooth type 3 organisms but not with rough type 1R or 2R cells. PSP-3R immune serum was tested in a passive hemagglutination assay against type 3 capsular polysaccharide-coated erythrocytes and found to have no detectable anticapsular antibody. The possible identity of the immunogen (s) in the vaccine is discussed.", "contents": "Biological properties of an immunogenic pneumococcal subcellular preparation. A subcellular fraction, designated PSP-3R, prepared from rough, type 3R Streptococcus pneumoniae is described, which affords excellent protection to mice against challenge with smooth organisms of the homologous serotype 3S and significant protection against heterologous challenge with serotypes 1S and 2S. Adjuvant enhances the protective capacity of the vaccine but is not necessary for immunogenicity. Protection induced by PSP-3R can be passively transferred tp normal mice with serum from actively immunized animals. The protective capacity can be completely absorbed out with rough or smooth type 3 organisms but not with rough type 1R or 2R cells. PSP-3R immune serum was tested in a passive hemagglutination assay against type 3 capsular polysaccharide-coated erythrocytes and found to have no detectable anticapsular antibody. The possible identity of the immunogen (s) in the vaccine is discussed."}
{"id": "PMID:5374", "title": "Nonspecific bactericidal activity of the lactoperoxidases-thiocyanate-hydrogen peroxide system of milk against Escherichia coli and some gram-negative pathogens.", "content": "Two strains of Escherichia coli and one strain each of Salmonella typhimurium and Pseudomonas aeruginosa were killed by the bactericidal activity of the lactoperoxidase-thiocyanate-hydrogen peroxide system in milk and in a synthetic medium. H2O2 was supplied exogenously by glucose oxidase, and glucose was produced at a level which was itself noninhibitory. Two phases were distinguished: the first phase was dependent on the oxidation of SCN(-) by lactoperoxidase and H2O2, which was reversed by reducing agent, and the second phase was dependent on the presence of accumulated H2O2, which was reversed by catalase. The latter enzyme could also reverse the first phase, but only when present in excessive and unphysiological levels. The bactericidal activity was greatest at pH 5 and below, and it depended on the SCN(-)concentration and on the number of organisms. Since raw or heated milk neutralizes the acid barrier against infection in the stomach, the bactericidal system discussed may contribute to the prevention of enteric infections in neonates.", "contents": "Nonspecific bactericidal activity of the lactoperoxidases-thiocyanate-hydrogen peroxide system of milk against Escherichia coli and some gram-negative pathogens. Two strains of Escherichia coli and one strain each of Salmonella typhimurium and Pseudomonas aeruginosa were killed by the bactericidal activity of the lactoperoxidase-thiocyanate-hydrogen peroxide system in milk and in a synthetic medium. H2O2 was supplied exogenously by glucose oxidase, and glucose was produced at a level which was itself noninhibitory. Two phases were distinguished: the first phase was dependent on the oxidation of SCN(-) by lactoperoxidase and H2O2, which was reversed by reducing agent, and the second phase was dependent on the presence of accumulated H2O2, which was reversed by catalase. The latter enzyme could also reverse the first phase, but only when present in excessive and unphysiological levels. The bactericidal activity was greatest at pH 5 and below, and it depended on the SCN(-)concentration and on the number of organisms. Since raw or heated milk neutralizes the acid barrier against infection in the stomach, the bactericidal system discussed may contribute to the prevention of enteric infections in neonates."}
{"id": "PMID:5375", "title": "Germination of Candida albicans induced by proline.", "content": "Blastospores of Candida albicans germinated in proline-biotin-buffer medium incubated at 37 C. Certain other amino acids in the glatamate, asparate, and pyruvate families also fostered germinaton but generally to a lesser extent than did proline. L-Cysteine, D-proline, and certain structural analogues of L-proline inhibited proline-stimualted germination. The concentration of phosphate and glucose was crucial to amino acid-stimulated germination of C. albicans. Clinical isolates and stock cultures varied in their response to the germ tube-inducing activity of proline or other amino acids. The proline-buffer medium cannot be used in a diagnostic test for production of germ tubes by isolates of yeasts.", "contents": "Germination of Candida albicans induced by proline. Blastospores of Candida albicans germinated in proline-biotin-buffer medium incubated at 37 C. Certain other amino acids in the glatamate, asparate, and pyruvate families also fostered germinaton but generally to a lesser extent than did proline. L-Cysteine, D-proline, and certain structural analogues of L-proline inhibited proline-stimualted germination. The concentration of phosphate and glucose was crucial to amino acid-stimulated germination of C. albicans. Clinical isolates and stock cultures varied in their response to the germ tube-inducing activity of proline or other amino acids. The proline-buffer medium cannot be used in a diagnostic test for production of germ tubes by isolates of yeasts."}
{"id": "PMID:5376", "title": "Partial purification and properties of Enterobacter cloacae heat-stable enterotoxin.", "content": "Cell free preparations of the whole-cell lysate and ultrafiltration (UF) fractions of broth cultures of a strain of Enterobacter cloacae, isolated from a Puerto Rican with tropical sprue, were assayed for their ability to induce in vivo net water secretion in the rat jejunum. The whole-cell lysate and UM-10 retentate of broth cultures were inactive. The UM-2 retentate and filtrate were active at a concentration of 100 mug/ml or more; the toxigenic activity was entirely retained, and increased to 1 mug/ml, by a UM-05 membrane; washing this retentate yielded a fraction with an activity of 10 ng/ml. Stationary aerobic culture conditions yielded the most active UF fractions when ammonium sulfate was used as the precipitating agent, whereas anaerobic culture conditions produced the most active fractions in broth cultures precipitated by acetone. Passage of the active acetone-precipitated UF fractions through a Sephadex G-25 column yielded eluate pools with enhanced toxigenic activity in, or adjacent to, the void volume, but maximum activity of the ammonium sulfate-precipitated UM-05 retentate eluated at a Kav of 0.38 to 0.52. Neither of the most active gel filtration elution fractions of the UM-05 retentates contained detectable carbohydrate, suggesting that the toxin is not associated with endotoxin. Toxigenic activity was unaltered by exposure to a temperature of 100C for 30 min, lowering the pH to 1, or incubation with either Pronase or trypsin. These observations indicate that the strain of E. cloacae under study elaborates a heat-stable enterotoxin htat has approximately the same molecular weight and shares many of the characteristics of the heat-stable enterotoxin produced by some strains of Escherichia coli and Klebsiella pneumoniae.", "contents": "Partial purification and properties of Enterobacter cloacae heat-stable enterotoxin. Cell free preparations of the whole-cell lysate and ultrafiltration (UF) fractions of broth cultures of a strain of Enterobacter cloacae, isolated from a Puerto Rican with tropical sprue, were assayed for their ability to induce in vivo net water secretion in the rat jejunum. The whole-cell lysate and UM-10 retentate of broth cultures were inactive. The UM-2 retentate and filtrate were active at a concentration of 100 mug/ml or more; the toxigenic activity was entirely retained, and increased to 1 mug/ml, by a UM-05 membrane; washing this retentate yielded a fraction with an activity of 10 ng/ml. Stationary aerobic culture conditions yielded the most active UF fractions when ammonium sulfate was used as the precipitating agent, whereas anaerobic culture conditions produced the most active fractions in broth cultures precipitated by acetone. Passage of the active acetone-precipitated UF fractions through a Sephadex G-25 column yielded eluate pools with enhanced toxigenic activity in, or adjacent to, the void volume, but maximum activity of the ammonium sulfate-precipitated UM-05 retentate eluated at a Kav of 0.38 to 0.52. Neither of the most active gel filtration elution fractions of the UM-05 retentates contained detectable carbohydrate, suggesting that the toxin is not associated with endotoxin. Toxigenic activity was unaltered by exposure to a temperature of 100C for 30 min, lowering the pH to 1, or incubation with either Pronase or trypsin. These observations indicate that the strain of E. cloacae under study elaborates a heat-stable enterotoxin htat has approximately the same molecular weight and shares many of the characteristics of the heat-stable enterotoxin produced by some strains of Escherichia coli and Klebsiella pneumoniae."}
{"id": "PMID:5377", "title": "Further studies of the physical and metabolic properties of foot-and-mouth disease virus temperature-sensitive mutants.", "content": "Three temperature-sensitive (ts) mutants of foot-and-mouth disease virus were classified as ribonucleic acid negative and as belonging to the same complementation group when measured by virus yields and [3H] uridine incorporation in paired, mixed infections at the nonpermissive temperature (38.5C). Mutant ts-22, the only mutant able to produce plaques at 38.5 C, was more sensitive to acid than were the parental wild-type or other mutant viruses. Diethylaminoethyl-dextran did not enhance the plaque-forming ability of the mutant viruses at 38.5C. All of the viruses inhibited host cell protein syntehsis at both permissive (33C) and nonpermissive (38.5C) temperatures.", "contents": "Further studies of the physical and metabolic properties of foot-and-mouth disease virus temperature-sensitive mutants. Three temperature-sensitive (ts) mutants of foot-and-mouth disease virus were classified as ribonucleic acid negative and as belonging to the same complementation group when measured by virus yields and [3H] uridine incorporation in paired, mixed infections at the nonpermissive temperature (38.5C). Mutant ts-22, the only mutant able to produce plaques at 38.5 C, was more sensitive to acid than were the parental wild-type or other mutant viruses. Diethylaminoethyl-dextran did not enhance the plaque-forming ability of the mutant viruses at 38.5C. All of the viruses inhibited host cell protein syntehsis at both permissive (33C) and nonpermissive (38.5C) temperatures."}
{"id": "PMID:5378", "title": "Interaction of cholera toxin and toxin derivatives with lymphocytes. II. Modulating effects of cholera toxin on in vivo humoral and cellular immune responses.", "content": "The in vivo effects of cholera toxin on lymphoid organ structure and function in mice were investigated. It was found that within a day following intravenous injection of 1 mug of toxin, thymus as well as spleen weight decreased but the animals remained healthy. Histological studies suggested that the involution of lymphoid organs was due to cell death. Injection of cholera toxin into adrenalectomized mice was lethal within 36 h. In these animals no decrease in lymphoid organ weight was noted. Thymus cells from toxin-treated mice were found to be much inferior to thymocytes of untreated animals in their in vitro response to Concanavalin A, whereas the response of spleen cells from toxin-treated animals to mitogens was slightly increased. 1 mug of cholera toxin increased primary antibody formation when given to mice together with antigen (sheep erythrocytes) and decreased primary antibody formation when given before or after the antigen. The toxin also increased secondary antibody formation when injected simultaneously with or after the booster antigen dose, and decreased the antibody formation when given a few days before the booster injection. Treatment of mice with toxin was found to increase the capacity of spleen cells from these animals to induce the parental effect on antibody formation and to induce graft-versus-host reactions. The mechanisms behind the observed effects are discussed. It is suggested that cholera toxin affects different types of cells involved in immune responses primarily by a direct inhibitory action on cellular proliferation but also indirectly by causing release of adrenal gland hormones.", "contents": "Interaction of cholera toxin and toxin derivatives with lymphocytes. II. Modulating effects of cholera toxin on in vivo humoral and cellular immune responses. The in vivo effects of cholera toxin on lymphoid organ structure and function in mice were investigated. It was found that within a day following intravenous injection of 1 mug of toxin, thymus as well as spleen weight decreased but the animals remained healthy. Histological studies suggested that the involution of lymphoid organs was due to cell death. Injection of cholera toxin into adrenalectomized mice was lethal within 36 h. In these animals no decrease in lymphoid organ weight was noted. Thymus cells from toxin-treated mice were found to be much inferior to thymocytes of untreated animals in their in vitro response to Concanavalin A, whereas the response of spleen cells from toxin-treated animals to mitogens was slightly increased. 1 mug of cholera toxin increased primary antibody formation when given to mice together with antigen (sheep erythrocytes) and decreased primary antibody formation when given before or after the antigen. The toxin also increased secondary antibody formation when injected simultaneously with or after the booster antigen dose, and decreased the antibody formation when given a few days before the booster injection. Treatment of mice with toxin was found to increase the capacity of spleen cells from these animals to induce the parental effect on antibody formation and to induce graft-versus-host reactions. The mechanisms behind the observed effects are discussed. It is suggested that cholera toxin affects different types of cells involved in immune responses primarily by a direct inhibitory action on cellular proliferation but also indirectly by causing release of adrenal gland hormones."}
{"id": "PMID:5380", "title": "Electron paramagnetic resonance studies on spin-labelling of pepsin: effects of temperature, pH and urea on its conformation.", "content": "Pepsin was spin-labelled with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidyl) bromoacetamide, possibly at the active site, at a beta-catboxyl group of a reactive aspartic acid. The spectrum of the spin-labelled pepsin showed that the spin probe was strongly immobilized (correlation time is greater than or equal to 10(-8) sec). Spin-labelled pepsin was thermally denatured at various temperatures and electron paramagnetic resonance (e.p.r.) spectra were taken at various times. Rates of denaturation estimated from the e.p.r. spectra at various temperatures showed that the enthalpy and entropy of thermal denaturation of spin-labelled pepsin at pH 3.5 were 48.0+/-4.9 kcal/mole and 214.7+/-14.5 e.u. respectively. Addition of conc. NaOH or 1 M acetate buffer at pH 6.0 sharpened e.p.r. spectra of the spin-labelled pepsin, indicating that the spin probe became mobilized by alkaline denaturation. Addition of urea caused unfolding of the protein which increased with the urea concentration, although only slight transition of conformational changes was observed in the e.p.r. spectra.", "contents": "Electron paramagnetic resonance studies on spin-labelling of pepsin: effects of temperature, pH and urea on its conformation. Pepsin was spin-labelled with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidyl) bromoacetamide, possibly at the active site, at a beta-catboxyl group of a reactive aspartic acid. The spectrum of the spin-labelled pepsin showed that the spin probe was strongly immobilized (correlation time is greater than or equal to 10(-8) sec). Spin-labelled pepsin was thermally denatured at various temperatures and electron paramagnetic resonance (e.p.r.) spectra were taken at various times. Rates of denaturation estimated from the e.p.r. spectra at various temperatures showed that the enthalpy and entropy of thermal denaturation of spin-labelled pepsin at pH 3.5 were 48.0+/-4.9 kcal/mole and 214.7+/-14.5 e.u. respectively. Addition of conc. NaOH or 1 M acetate buffer at pH 6.0 sharpened e.p.r. spectra of the spin-labelled pepsin, indicating that the spin probe became mobilized by alkaline denaturation. Addition of urea caused unfolding of the protein which increased with the urea concentration, although only slight transition of conformational changes was observed in the e.p.r. spectra."}
{"id": "PMID:5381", "title": "Characterization of an alkaline subtilopeptidase type Pfizer.", "content": "The physiochemical properties, amino acid composition and profile of the the tryptic peptides for an alkaline subtilopeptidase type Pfizer have been determined. The enzyme is stable in the pH range from 5 to 10, has a pH optimum of 9.5 to 10, and is relatively stable for a period of 2 h up to a temperature of 50C. Homogeneity was demonstrated by electrophoretic techniques and the mobilities indicated on isoelectric point of 8.7. The molecular weight was found to be 25,000 by gel filtration. The amino acid composition was found to be Ala32, Arg4, Aspgamma8, Glu15, Gly29, His4, Ile9, Leu13, Lys11, Met5, Phe4, Pro14, Ser31, Thr17, Tyr9, Val22, a total of 247 amino acid residues. The enzyme does not contain either disulfide bonds or cysteine, and lacks tryptophan as well. The N-terminal end-group residue is alanine: the C-terminal amino acid is arginine. Tryptic hydrolysis of the enzyme produced 15 peptides which were separated by gradient elution on Dowex 50-X2. The amino acid composition of each appropriately purified tryptic peptide was established.", "contents": "Characterization of an alkaline subtilopeptidase type Pfizer. The physiochemical properties, amino acid composition and profile of the the tryptic peptides for an alkaline subtilopeptidase type Pfizer have been determined. The enzyme is stable in the pH range from 5 to 10, has a pH optimum of 9.5 to 10, and is relatively stable for a period of 2 h up to a temperature of 50C. Homogeneity was demonstrated by electrophoretic techniques and the mobilities indicated on isoelectric point of 8.7. The molecular weight was found to be 25,000 by gel filtration. The amino acid composition was found to be Ala32, Arg4, Aspgamma8, Glu15, Gly29, His4, Ile9, Leu13, Lys11, Met5, Phe4, Pro14, Ser31, Thr17, Tyr9, Val22, a total of 247 amino acid residues. The enzyme does not contain either disulfide bonds or cysteine, and lacks tryptophan as well. The N-terminal end-group residue is alanine: the C-terminal amino acid is arginine. Tryptic hydrolysis of the enzyme produced 15 peptides which were separated by gradient elution on Dowex 50-X2. The amino acid composition of each appropriately purified tryptic peptide was established."}
{"id": "PMID:5382", "title": "Psychosomatic studies of psychiatric disorders: schizophrenia.", "content": "This paper uses some of the data on central nervous dysfunction in schizophrenic patients as a paradigm for the integration of biologic data with psychopathologic conditions. As such, a good portion of the paper emphasizes the methodologic and interpretive problems one must consider in \"psychosomatic\" studies of mental illness. A possible theory to integrate these findings is presented.", "contents": "Psychosomatic studies of psychiatric disorders: schizophrenia. This paper uses some of the data on central nervous dysfunction in schizophrenic patients as a paradigm for the integration of biologic data with psychopathologic conditions. As such, a good portion of the paper emphasizes the methodologic and interpretive problems one must consider in \"psychosomatic\" studies of mental illness. A possible theory to integrate these findings is presented."}
{"id": "PMID:5383", "title": "Biofeedback and self-control of physiological functions: clinical applications.", "content": "The parameters amenable to biofeedback learning are mentioned, including brainwaves, muscle tension, temperature, the cardiovascular system, and others. A discussion follows of the clinical application of biofeedback in the treatment of such disorders as tension headaches, neuromuscular re-education, epilepsy, \"dysponesis,\" cardiac arrhythmias, blood pressure and migraines. The usefulness of biofeedback has been demonstrated also in the field of psychotherapy for purposes of desensitization, treating anxious patients, encouraging specific personality changes, and indicating stress to patients.", "contents": "Biofeedback and self-control of physiological functions: clinical applications. The parameters amenable to biofeedback learning are mentioned, including brainwaves, muscle tension, temperature, the cardiovascular system, and others. A discussion follows of the clinical application of biofeedback in the treatment of such disorders as tension headaches, neuromuscular re-education, epilepsy, \"dysponesis,\" cardiac arrhythmias, blood pressure and migraines. The usefulness of biofeedback has been demonstrated also in the field of psychotherapy for purposes of desensitization, treating anxious patients, encouraging specific personality changes, and indicating stress to patients."}
{"id": "PMID:5384", "title": "Psychophysiology of pain.", "content": "The recent literature on pain states shows: pain thresholds are relatively constant for an individual, but pain tolerance is influenced by psychological state; the expression of pain is a function partly of ethnic membership and degree of extroversion; pain complaints are determined as well by cultural and extroversive factors, and also degree of neuroticism. Studies of pain patients reveals that those with acute pain tend to show normal personality profiles, but the degree of pain experienced is related to the degree of anxiety present. Most chronic pain patients, like those with psychogenic pain, show somatic preoccupations and reactive depression. The treatment and/or rehabilitation of pain patients has developed in three areas. In cases of peripheral neuropathy and some spinal cord lesions, electrical stimulation with \"neural pacemakers\" can often \"close the gate\" to pain signals and provide significant reduction or abolition of pain. Psychotropic medications, particularly the tricyclic antidepressants, sometimes in combination with phenothiazines and antihistamines, are effective in many instances of central pain, and help increase the pain tolerance and decrease the need for narcotics in other pain states. Operant conditioning, including the use of biofeedback, extinguishes pain behavior and increases pain-incompatible behaviors, with good long-term results.", "contents": "Psychophysiology of pain. The recent literature on pain states shows: pain thresholds are relatively constant for an individual, but pain tolerance is influenced by psychological state; the expression of pain is a function partly of ethnic membership and degree of extroversion; pain complaints are determined as well by cultural and extroversive factors, and also degree of neuroticism. Studies of pain patients reveals that those with acute pain tend to show normal personality profiles, but the degree of pain experienced is related to the degree of anxiety present. Most chronic pain patients, like those with psychogenic pain, show somatic preoccupations and reactive depression. The treatment and/or rehabilitation of pain patients has developed in three areas. In cases of peripheral neuropathy and some spinal cord lesions, electrical stimulation with \"neural pacemakers\" can often \"close the gate\" to pain signals and provide significant reduction or abolition of pain. Psychotropic medications, particularly the tricyclic antidepressants, sometimes in combination with phenothiazines and antihistamines, are effective in many instances of central pain, and help increase the pain tolerance and decrease the need for narcotics in other pain states. Operant conditioning, including the use of biofeedback, extinguishes pain behavior and increases pain-incompatible behaviors, with good long-term results."}
{"id": "PMID:5388", "title": "[Foot tendon dislocations].", "content": "Two luxations of the tendon of the Peroneus longus and one luxation of the Tibialis posterior muscle are reported. All the three cases had a traumatical cause and none of them showed symptoms of dysplasia. That is why a simple reconstruction of the retinaculum strengthened by a flap of the periost seemed to be justified. One year after the operation good results were verified by controls, therefore the method may be recommended for similar cases.", "contents": "[Foot tendon dislocations]. Two luxations of the tendon of the Peroneus longus and one luxation of the Tibialis posterior muscle are reported. All the three cases had a traumatical cause and none of them showed symptoms of dysplasia. That is why a simple reconstruction of the retinaculum strengthened by a flap of the periost seemed to be justified. One year after the operation good results were verified by controls, therefore the method may be recommended for similar cases."}
{"id": "PMID:5389", "title": "Simultaneous pH and fluoride telemetry. A supplemental report.", "content": "Simultaneous telemetry of salivary fluoride and of interproximal plaqua pH at the entrance to an interproximal space was used to investigate the effects of sucrose-containing fluoride tablets dissolving in the vicinity of the fluoride and pH sensors. The dissolving of 1.0 mg fluoride-42 mg sucrose tablets caused only slight pH depressions ranging between 6.7 and 6.0 with concurrent increases in salivary F to as high as 190 ppm. Acid formation in interproximal plaque by fluoride-free, sucrose-containing placebo tablets decreased pH to 4.2.", "contents": "Simultaneous pH and fluoride telemetry. A supplemental report. Simultaneous telemetry of salivary fluoride and of interproximal plaqua pH at the entrance to an interproximal space was used to investigate the effects of sucrose-containing fluoride tablets dissolving in the vicinity of the fluoride and pH sensors. The dissolving of 1.0 mg fluoride-42 mg sucrose tablets caused only slight pH depressions ranging between 6.7 and 6.0 with concurrent increases in salivary F to as high as 190 ppm. Acid formation in interproximal plaque by fluoride-free, sucrose-containing placebo tablets decreased pH to 4.2."}
{"id": "PMID:5385", "title": "Isolations in a mosquito (Aedes pseudoscutellaris) cell line (Mos. 61) of yellow fever virus strains from original field material.", "content": "A simple, rapid and inexpensive method of isolating yellow fever (YF) virus from naturally infected mosquitoes, human liver and the serum of a sentinel monkey by inoculation of a continuous line of mosquito cells is described. The mosquito cells were more sensitive than suckling mice and marginally better than Vero cells for primary isolation. This is the first time that mosquito cells have been successfully used for primary isolation of YF virus from field material.", "contents": "Isolations in a mosquito (Aedes pseudoscutellaris) cell line (Mos. 61) of yellow fever virus strains from original field material. A simple, rapid and inexpensive method of isolating yellow fever (YF) virus from naturally infected mosquitoes, human liver and the serum of a sentinel monkey by inoculation of a continuous line of mosquito cells is described. The mosquito cells were more sensitive than suckling mice and marginally better than Vero cells for primary isolation. This is the first time that mosquito cells have been successfully used for primary isolation of YF virus from field material."}
{"id": "PMID:5390", "title": "The effect of sorbose on pH of mixed saliva and interproximal plaque.", "content": "Stimulated mixed saliva and interproximal plaque were exposed to the ketohexose sorbose. The average pH of an in vitro 1%-sorbose/saliva mixture increased with time when compared with a highly significant pH-decrease of a sucrose/saliva mixture. In contrast to sucrose rinses, the telemetrically recorded pH of interproximal plaque did not drop below pH 5.5 during and subsequent to rinsing with sorbose solutions.", "contents": "The effect of sorbose on pH of mixed saliva and interproximal plaque. Stimulated mixed saliva and interproximal plaque were exposed to the ketohexose sorbose. The average pH of an in vitro 1%-sorbose/saliva mixture increased with time when compared with a highly significant pH-decrease of a sucrose/saliva mixture. In contrast to sucrose rinses, the telemetrically recorded pH of interproximal plaque did not drop below pH 5.5 during and subsequent to rinsing with sorbose solutions."}
{"id": "PMID:5395", "title": "Comparison of antibiotic-amended potato dextrose agar and acidified potato dextrose agar as growth substrates for fungi.", "content": "Fifteen fungal species, all isolated from food, were compared for their growth abilities on potato dextrose agar acidified to pH 3.5, and on nonacidified potato dextrose agar amended with 40 ppm chlortetracycline hydrochloride. Comparisons were made at 16, 21, 26, 32, and 37 degrees C. Of the 15 species, only Penicillium expansum exhibited better growth on the acidified medium than on the nonacidified antibiotic medium, while 9 species grew better on the nonacidified antibiotic medium. Five species grew equally well on either medium.", "contents": "Comparison of antibiotic-amended potato dextrose agar and acidified potato dextrose agar as growth substrates for fungi. Fifteen fungal species, all isolated from food, were compared for their growth abilities on potato dextrose agar acidified to pH 3.5, and on nonacidified potato dextrose agar amended with 40 ppm chlortetracycline hydrochloride. Comparisons were made at 16, 21, 26, 32, and 37 degrees C. Of the 15 species, only Penicillium expansum exhibited better growth on the acidified medium than on the nonacidified antibiotic medium, while 9 species grew better on the nonacidified antibiotic medium. Five species grew equally well on either medium."}
{"id": "PMID:5397", "title": "Luminescence and respiratory activities of Photobacterium phosphoreum. Competition for cellular reducing power.", "content": "Changes in the in vivo luminescence, respiratory activities, contents of cytochromes, extractable luciferase and NAD(P)H-FMN reductase during growth of the wild (bright) strain of Photobacterium phosphoreum and its dim mutant were determined. The intensity of the in vivo luminescence per cell increased 10 times in the wild strain and 750 times in the dim strain during logarithmic growth, while the contents of luciferase and NAD(P)H-FMN reductase remained almost constant. It is suggested that a characteristic change in the mode of competition of the luminescence reaction system with another electron transfer chain involving cytochromes for NAD(P)H take place during the growth of this bacterium.", "contents": "Luminescence and respiratory activities of Photobacterium phosphoreum. Competition for cellular reducing power. Changes in the in vivo luminescence, respiratory activities, contents of cytochromes, extractable luciferase and NAD(P)H-FMN reductase during growth of the wild (bright) strain of Photobacterium phosphoreum and its dim mutant were determined. The intensity of the in vivo luminescence per cell increased 10 times in the wild strain and 750 times in the dim strain during logarithmic growth, while the contents of luciferase and NAD(P)H-FMN reductase remained almost constant. It is suggested that a characteristic change in the mode of competition of the luminescence reaction system with another electron transfer chain involving cytochromes for NAD(P)H take place during the growth of this bacterium."}
{"id": "PMID:5398", "title": "Purification and characterization of inorganic pyrophosphatase from Bacillus stearothermophilus.", "content": "Inorganic pyrophosphatase [EC 3.6.1.1] was purified from Bacillus stearothermophilus to a homogeneous state both ultracentrifugally and electrophoretically. Ultracentrifugal analysis revealed that the molecular weight of the enzyme is 122,000 and the sedimentation coefficient (S0.34%/20, W) is 5.2S. The enzyme molecule in 0.1% sodium dodecylsulfate solution containing 1 mM 2-mercaptoethanol had an estimated molecular weight of 70,000 on the basis of SDS-polyacrylamide gel electrophoresis results, which indicates that the enzyme may consist of two subunits. Divalent cations such as Mg2+, Mn2+, and Co2+ are required for the enzymatic activity. Pyrophosphate is the only substrate for the enzyme. ATP and p-chloromercuribenzoate inhibit the enzyme reaction markedly.", "contents": "Purification and characterization of inorganic pyrophosphatase from Bacillus stearothermophilus. Inorganic pyrophosphatase [EC 3.6.1.1] was purified from Bacillus stearothermophilus to a homogeneous state both ultracentrifugally and electrophoretically. Ultracentrifugal analysis revealed that the molecular weight of the enzyme is 122,000 and the sedimentation coefficient (S0.34%/20, W) is 5.2S. The enzyme molecule in 0.1% sodium dodecylsulfate solution containing 1 mM 2-mercaptoethanol had an estimated molecular weight of 70,000 on the basis of SDS-polyacrylamide gel electrophoresis results, which indicates that the enzyme may consist of two subunits. Divalent cations such as Mg2+, Mn2+, and Co2+ are required for the enzymatic activity. Pyrophosphate is the only substrate for the enzyme. ATP and p-chloromercuribenzoate inhibit the enzyme reaction markedly."}
{"id": "PMID:5399", "title": "Studies on peroxisomes. V. Effect of ethyl p-chlorophenoxyisobutyrate on the centrifugal behavior of rat liver peroxisomes.", "content": "After Wistar male rats had been fed on a diet containing 0.25% of ethyl p-chlorophenoxyisobutyrate (CPIB) for 28 days, changes in the enzyme activities and centrifugal behavior of rat liver peroxisomes were investigated. (1) Compared with control rats fed on the basal diet, the catalase [EC 1.11.1.6] activity of rat livers after the administration of CPIB increased about 2.5-fold, while urate oxidase [EC 1.7.3.3] activity did not change significantly. Though D-amino acid oxidase [EC 1.4.3.3] activity markedly decreased to approximately one-sixth of the control, the activity of L-alpha-hydroxy acid oxidase [EC 1.1.3.15], a flavin enzyme like D-amino acid oxidase, was not affected significnatly after the administration of CPIB. (2) When the hepatic cells of CPIB-treated rats were fractionated by differential centrifugation, most of the increase of catalase activity appeared in the supernatant fraction. A decrease in the hepatic D-amino acid oxidase activity of CPIB-treated rats was observed in all the fractions. As for the subcellular distribution of the particle-bound enzymes, the specific activities of both catalase and urate oxidase of CPIB-treated rat livers were higher in the light mitochondrial fraction than in other fractions. (3) Sedimentation patterns in a sucrose density gradient did not show any difference between normal peroxisomers, and CPIB-treated ones. (4) In the case of CPIB-treated rats, studies of their sedimentation patterns by Ficoll density gradient centrifugation showed two main particulate peaks containing both catalase and urate oxidase, although only a single peak was observed in the case of control rats.", "contents": "Studies on peroxisomes. V. Effect of ethyl p-chlorophenoxyisobutyrate on the centrifugal behavior of rat liver peroxisomes. After Wistar male rats had been fed on a diet containing 0.25% of ethyl p-chlorophenoxyisobutyrate (CPIB) for 28 days, changes in the enzyme activities and centrifugal behavior of rat liver peroxisomes were investigated. (1) Compared with control rats fed on the basal diet, the catalase [EC 1.11.1.6] activity of rat livers after the administration of CPIB increased about 2.5-fold, while urate oxidase [EC 1.7.3.3] activity did not change significantly. Though D-amino acid oxidase [EC 1.4.3.3] activity markedly decreased to approximately one-sixth of the control, the activity of L-alpha-hydroxy acid oxidase [EC 1.1.3.15], a flavin enzyme like D-amino acid oxidase, was not affected significnatly after the administration of CPIB. (2) When the hepatic cells of CPIB-treated rats were fractionated by differential centrifugation, most of the increase of catalase activity appeared in the supernatant fraction. A decrease in the hepatic D-amino acid oxidase activity of CPIB-treated rats was observed in all the fractions. As for the subcellular distribution of the particle-bound enzymes, the specific activities of both catalase and urate oxidase of CPIB-treated rat livers were higher in the light mitochondrial fraction than in other fractions. (3) Sedimentation patterns in a sucrose density gradient did not show any difference between normal peroxisomers, and CPIB-treated ones. (4) In the case of CPIB-treated rats, studies of their sedimentation patterns by Ficoll density gradient centrifugation showed two main particulate peaks containing both catalase and urate oxidase, although only a single peak was observed in the case of control rats."}
{"id": "PMID:5400", "title": "Purification and characterization of pyruvate decarboxylase from sweet potato roots.", "content": "Pyruvate decarboxylase [2-oxo acid carboxy-lyase, EC 4.1.1.1] was isolated from sweet potato roots and was partially purified from healthy and diseased tissues. There was no appreciable difference in properties between the enzymes from healthy and diseased tissues. The molecular weight of the enzyme was found to be 240,000 by polyacrylamide gel electrophoresis. Since sodium dodecyl sulfate polyacrylamide gel electrophoresis gave a molecular weight of 60,000 for the monomeric form of the enzyme, it is likely that sweet potato pyruvate decarboxylase contains 4 single polypeptide chains. The optimal pH of the decarboxylation reaction was 6.1--6.6. The Lineweaver-Burk double reciprocal plot curved upward, and the Hill coefficient was more than 1, with low concentrations of pyruvate. The enzyme was localized in the cytosol fraction. The activity of the enzyme increased in response to black-rot fungus infection, but decreased in response to cutting.", "contents": "Purification and characterization of pyruvate decarboxylase from sweet potato roots. Pyruvate decarboxylase [2-oxo acid carboxy-lyase, EC 4.1.1.1] was isolated from sweet potato roots and was partially purified from healthy and diseased tissues. There was no appreciable difference in properties between the enzymes from healthy and diseased tissues. The molecular weight of the enzyme was found to be 240,000 by polyacrylamide gel electrophoresis. Since sodium dodecyl sulfate polyacrylamide gel electrophoresis gave a molecular weight of 60,000 for the monomeric form of the enzyme, it is likely that sweet potato pyruvate decarboxylase contains 4 single polypeptide chains. The optimal pH of the decarboxylation reaction was 6.1--6.6. The Lineweaver-Burk double reciprocal plot curved upward, and the Hill coefficient was more than 1, with low concentrations of pyruvate. The enzyme was localized in the cytosol fraction. The activity of the enzyme increased in response to black-rot fungus infection, but decreased in response to cutting."}
{"id": "PMID:5401", "title": "Quantitative determination of anomeric forms of sugar produced by amylases. V. Anomeric forms of maltose produced in the hydrolytic reaction of substituted phenyl alpha-maltosides catalyzed by saccharifying alpha-amylase from B. subtilis.", "content": "1. Hydrolyses of phenyl alpha-maltoside and its derivatives with various substituents (p-NO2, p-C1, p-CH3, p-C2H5, and p-C(CH3)3) catalyzed by saccharifying alpha-amylase from B. subtilis3 [EC 3.2.1.1] were studied under conditions such that the products were only maltose and the corresponding phenols (1), in order to determine quantitatively the anomeric form of the sugar produced from each substrate. 2. At the optimum pH of this enzyme (pH-5.4), maltose released from all the substituted substrates studied was entirely in the beta-form. These results are in remarkable contrast to the previous finding that alpha-maltose is exclusively produced from unsubstituted phenyl alpha-maltoside by this enzyme (2). 3. At pH 6.18 and 6.73, maltose produced from unsubstituted phenyl alpha-maltoside (\u00f8M) or p-tert-butylphenyl alpha-maltoside (PTB\u00f8M) was a mixture of alpha- and beta-anomers, the ratio being dependent on pH as follows: For \u00f8M, the percentage of alpha-anomer was 100% (pH 5.4), 80 (pH 6.18), and 55% (pH 6.73), whereas for PTB\u00f8M, the percentage of beta-anomer was 100% (pH 5.4), 75% (pH 6.18), and 60% (pH 6.73).", "contents": "Quantitative determination of anomeric forms of sugar produced by amylases. V. Anomeric forms of maltose produced in the hydrolytic reaction of substituted phenyl alpha-maltosides catalyzed by saccharifying alpha-amylase from B. subtilis. 1. Hydrolyses of phenyl alpha-maltoside and its derivatives with various substituents (p-NO2, p-C1, p-CH3, p-C2H5, and p-C(CH3)3) catalyzed by saccharifying alpha-amylase from B. subtilis3 [EC 3.2.1.1] were studied under conditions such that the products were only maltose and the corresponding phenols (1), in order to determine quantitatively the anomeric form of the sugar produced from each substrate. 2. At the optimum pH of this enzyme (pH-5.4), maltose released from all the substituted substrates studied was entirely in the beta-form. These results are in remarkable contrast to the previous finding that alpha-maltose is exclusively produced from unsubstituted phenyl alpha-maltoside by this enzyme (2). 3. At pH 6.18 and 6.73, maltose produced from unsubstituted phenyl alpha-maltoside (\u00f8M) or p-tert-butylphenyl alpha-maltoside (PTB\u00f8M) was a mixture of alpha- and beta-anomers, the ratio being dependent on pH as follows: For \u00f8M, the percentage of alpha-anomer was 100% (pH 5.4), 80 (pH 6.18), and 55% (pH 6.73), whereas for PTB\u00f8M, the percentage of beta-anomer was 100% (pH 5.4), 75% (pH 6.18), and 60% (pH 6.73)."}
{"id": "PMID:5402", "title": "Studies on a phospholipase B from Penicillium notatum. Purification, properties, and mode of action.", "content": "1. Phospholipase B which hydrolyzes both the acyl ester bonds of diacylphospholipids (diacyl-hydrolase) and the acyl ester bond of monoacylphospholipids or lysophospholipids, [monoacyl-hydrolase or lysophospholipase, EC 3.1.1.5] was purified from Penicillium notatum about 2000-fold over the crude extract. The final preparation was homogeneous on disc electrophoresis. The apparent molecular weight, determined by gel filtration on Sephadex G-200, was about 116,000. The isoelectric point was pH 4.0. 2. The purified enzyme was a glycoprotein. The carbohydrate content was approximately 30%, consisting of mannose, glucose, and glucosamine. The amino acid composition was also determined. 3. The ratio of monoacyl-hydrolase to diacyl-hydrolase activities was influenced by the physical state of the substrate in the assay system. It was about 1 : 1 or 100 : 1 in the presence of absence of Triton X-100, respectively, and the latter value remained constant throughout the purification procedures. 4. Both enzyme activities had the same pH optimum, 4.0, and were heat-labile. None of the metals tested had any effect on either activity except for Fe2+ and Fe3+. Diisopropyl fluorophosphate at relatively high concentrations completely inhibited both enzyme activities. 5. The Michaelis-Menten constants (Km) of the enzyme for egg lecithin were about 1.5 and 25 mM in the absence and presence of Triton X-100, respectively. The Km value for dicaproyllecithin was 9.8 mM in the absence of Triton X-100. 6. Using a mixture of 1-[14C]stearoyl-lecithin and 2-[14C]oleoyl-lecithin in the presence of Triton X-100 as a substrate, it was found that the P. notatum phospholipase B attacked the acyl ester bonds sequentially, first the 2-acyl and then 1-acyl groups.", "contents": "Studies on a phospholipase B from Penicillium notatum. Purification, properties, and mode of action. 1. Phospholipase B which hydrolyzes both the acyl ester bonds of diacylphospholipids (diacyl-hydrolase) and the acyl ester bond of monoacylphospholipids or lysophospholipids, [monoacyl-hydrolase or lysophospholipase, EC 3.1.1.5] was purified from Penicillium notatum about 2000-fold over the crude extract. The final preparation was homogeneous on disc electrophoresis. The apparent molecular weight, determined by gel filtration on Sephadex G-200, was about 116,000. The isoelectric point was pH 4.0. 2. The purified enzyme was a glycoprotein. The carbohydrate content was approximately 30%, consisting of mannose, glucose, and glucosamine. The amino acid composition was also determined. 3. The ratio of monoacyl-hydrolase to diacyl-hydrolase activities was influenced by the physical state of the substrate in the assay system. It was about 1 : 1 or 100 : 1 in the presence of absence of Triton X-100, respectively, and the latter value remained constant throughout the purification procedures. 4. Both enzyme activities had the same pH optimum, 4.0, and were heat-labile. None of the metals tested had any effect on either activity except for Fe2+ and Fe3+. Diisopropyl fluorophosphate at relatively high concentrations completely inhibited both enzyme activities. 5. The Michaelis-Menten constants (Km) of the enzyme for egg lecithin were about 1.5 and 25 mM in the absence and presence of Triton X-100, respectively. The Km value for dicaproyllecithin was 9.8 mM in the absence of Triton X-100. 6. Using a mixture of 1-[14C]stearoyl-lecithin and 2-[14C]oleoyl-lecithin in the presence of Triton X-100 as a substrate, it was found that the P. notatum phospholipase B attacked the acyl ester bonds sequentially, first the 2-acyl and then 1-acyl groups."}
{"id": "PMID:5403", "title": "Substrate specificity of carboxypeptidase from Watermelon.", "content": "The substrate specificity of carboxypeptidase (F-II) purified from watermelon for various synthetic peptides and esters was examined kinetically. The enzyme showed a broad substrate specificity against various carbobenzoxy- and benzyl-dipeptides. Peptides containing glycine or proline were hydrolyzed slowly by the enzyme. Peptides containing hydrophobic amino acids were hydrolyzed rapidly. The presence of hydrophobic amino acid residues, not only at the C-terminal position but also at the second position and probably the third position from the C-terminal resulted in an increase in the rate of hydrolysis. Inhibition studies with diisopropyl flurophosphate and diastereomers of carbobenzoxy-Phe-Ala demonstrated that the peptidase and esterase activities of the enzyme are both catalyzed by the same site of the enzyme molecule, but the binding sites for peptides and esters seem not to be the same. The enzyme also had amidase activity, which was optimal at pH 7.0.", "contents": "Substrate specificity of carboxypeptidase from Watermelon. The substrate specificity of carboxypeptidase (F-II) purified from watermelon for various synthetic peptides and esters was examined kinetically. The enzyme showed a broad substrate specificity against various carbobenzoxy- and benzyl-dipeptides. Peptides containing glycine or proline were hydrolyzed slowly by the enzyme. Peptides containing hydrophobic amino acids were hydrolyzed rapidly. The presence of hydrophobic amino acid residues, not only at the C-terminal position but also at the second position and probably the third position from the C-terminal resulted in an increase in the rate of hydrolysis. Inhibition studies with diisopropyl flurophosphate and diastereomers of carbobenzoxy-Phe-Ala demonstrated that the peptidase and esterase activities of the enzyme are both catalyzed by the same site of the enzyme molecule, but the binding sites for peptides and esters seem not to be the same. The enzyme also had amidase activity, which was optimal at pH 7.0."}
{"id": "PMID:5404", "title": "Further confirmation of carboxypeptidase Y as a metal-free enzyme having a reactive serine residue.", "content": "The metal content of carboxypeptidase Y was analyzed by the atomic absorption method. After exhaustive dialysis against an EDTA solution, the enzyme showed no loss of activity nor any significant content of metals (Zh,Mg,Ca,Cu,Mn,Ni,Fe, and Co). The activity was, however, rather sensitive to preincubation with various metals. The reactivity of a serine residue of the enzyme was also reevaluated. Diisopropyl fluorophosphate (DFP) and phenylmethanesulfonyl fluoride (PMSF) stoichiometrically and irreversively inhibited the enzyme. The rate of inactivation with DFP was much faster than that for typsin [EC 3.4.21.4] and chymotrypsin [EC 3.4.21.1.], while the rate with PMSF was one-fifteenth of that for chymotrypsin. The pH-dependence of the inactivation by DFP was similar to that of the enzymatic hydrolysis of acetylphenylalanine ethyl ester. The present results indicate that carboxypeptidase Y is free of metals and has a serine residue with a vital role in the catalytic process, though the functional role of this SH group remains to be clarified.", "contents": "Further confirmation of carboxypeptidase Y as a metal-free enzyme having a reactive serine residue. The metal content of carboxypeptidase Y was analyzed by the atomic absorption method. After exhaustive dialysis against an EDTA solution, the enzyme showed no loss of activity nor any significant content of metals (Zh,Mg,Ca,Cu,Mn,Ni,Fe, and Co). The activity was, however, rather sensitive to preincubation with various metals. The reactivity of a serine residue of the enzyme was also reevaluated. Diisopropyl fluorophosphate (DFP) and phenylmethanesulfonyl fluoride (PMSF) stoichiometrically and irreversively inhibited the enzyme. The rate of inactivation with DFP was much faster than that for typsin [EC 3.4.21.4] and chymotrypsin [EC 3.4.21.1.], while the rate with PMSF was one-fifteenth of that for chymotrypsin. The pH-dependence of the inactivation by DFP was similar to that of the enzymatic hydrolysis of acetylphenylalanine ethyl ester. The present results indicate that carboxypeptidase Y is free of metals and has a serine residue with a vital role in the catalytic process, though the functional role of this SH group remains to be clarified."}
{"id": "PMID:5405", "title": "Inhibition of polypeptide synthesis by tRNA fractions in rat liver cell-free systems.", "content": "The mechanism of inhibition of polypeptide synthesis by the addition of a tRNA fraction in a rat liver cell-free system was studied. The inhibition was found to occur at the step of aminoacyl-tRNA binding to ribosomes, in which aminoacyl-tRNA's were mainly responsible for the inhibition. The addition of EF-1 decreased the inhibition by the tRNA fraction. The tRNA fraction inhibited polypeptide synthesis in a polysome-S100 system under conditions in which poly U- and poly A-dependent polypeptide syntheses were not inhibited. The possibility that the aminoacyl-tRNA inhibitory activity functions through improper binding to the ribosomes in the polysome-S100 system is discussed.", "contents": "Inhibition of polypeptide synthesis by tRNA fractions in rat liver cell-free systems. The mechanism of inhibition of polypeptide synthesis by the addition of a tRNA fraction in a rat liver cell-free system was studied. The inhibition was found to occur at the step of aminoacyl-tRNA binding to ribosomes, in which aminoacyl-tRNA's were mainly responsible for the inhibition. The addition of EF-1 decreased the inhibition by the tRNA fraction. The tRNA fraction inhibited polypeptide synthesis in a polysome-S100 system under conditions in which poly U- and poly A-dependent polypeptide syntheses were not inhibited. The possibility that the aminoacyl-tRNA inhibitory activity functions through improper binding to the ribosomes in the polysome-S100 system is discussed."}
{"id": "PMID:5406", "title": "alpha-Chymotryptic hydrolysis of derivatives of the specific substrates with substituents in the nucleus.", "content": "Steady state kinetic studies of alpha-chymotrypsin [EC 3.4.21.1]-catalyzed hydrolysis of nucleus-substituted derivatives of the specific substrates were made at pH 6.5 and 7.8. Ac-Trp(NCps)-OMe was hydrolyzed more readily than Ac-Trp-OMe owing to its smaller Km value. The kcat values of Ac-Trp(CHO)-OMe and Ac-Tyr(3-no2)-ome were higher than those of the corresponding unmodified substrates, suggesting that derivatives with a substituent as large as a formyl or nitro group at the epsilon-position are stereochemically favorable to the catalytic process. Derivatives of Ac-Phe-OMe with a chain of four atoms at the 3 or 4-position of the phenyl nucleus and 2,3-dihydropyrrolo[2,3-b]indoles derived from Ac-Trp-OMe were not hydrolyzed at all.", "contents": "alpha-Chymotryptic hydrolysis of derivatives of the specific substrates with substituents in the nucleus. Steady state kinetic studies of alpha-chymotrypsin [EC 3.4.21.1]-catalyzed hydrolysis of nucleus-substituted derivatives of the specific substrates were made at pH 6.5 and 7.8. Ac-Trp(NCps)-OMe was hydrolyzed more readily than Ac-Trp-OMe owing to its smaller Km value. The kcat values of Ac-Trp(CHO)-OMe and Ac-Tyr(3-no2)-ome were higher than those of the corresponding unmodified substrates, suggesting that derivatives with a substituent as large as a formyl or nitro group at the epsilon-position are stereochemically favorable to the catalytic process. Derivatives of Ac-Phe-OMe with a chain of four atoms at the 3 or 4-position of the phenyl nucleus and 2,3-dihydropyrrolo[2,3-b]indoles derived from Ac-Trp-OMe were not hydrolyzed at all."}
{"id": "PMID:5407", "title": "Intracellular pH (pHi) of red cells stored in acid citrate dextrose medium. Effects of temperature and citrate anions.", "content": "The intracellular pH (pHi) of red cells stored in acid citrate dextrose (ACD) medium was estimated by the 5,5'-dimethyloxazoldine,-2,4-dione (DMO) method. The initial pHi at 4degrees was about 7.6 and was higher than the extracellular pH (pHe) at 4degrees. During storage, both pHi and pHe decreased, but the former was always higher than the latter and the former decreased more slowly than the latter. The high pHi of ACD blood was a results of the temperature at which the pHe and the pHi were measured (4degrees) and the presence of citrate anions in the medium, and could be explained by application of the Donnan-Gibbs equilibrium. ATP and 2,3-diphosphoglycerate (DPG) were well-maintained in heparinized blood when it was acidified and pHe and pHi at 4degrees were both about 7.4, which suggests that improvement of blood preservation may be attained by suitable adjustment of the pHi and pHe of the blood.", "contents": "Intracellular pH (pHi) of red cells stored in acid citrate dextrose medium. Effects of temperature and citrate anions. The intracellular pH (pHi) of red cells stored in acid citrate dextrose (ACD) medium was estimated by the 5,5'-dimethyloxazoldine,-2,4-dione (DMO) method. The initial pHi at 4degrees was about 7.6 and was higher than the extracellular pH (pHe) at 4degrees. During storage, both pHi and pHe decreased, but the former was always higher than the latter and the former decreased more slowly than the latter. The high pHi of ACD blood was a results of the temperature at which the pHe and the pHi were measured (4degrees) and the presence of citrate anions in the medium, and could be explained by application of the Donnan-Gibbs equilibrium. ATP and 2,3-diphosphoglycerate (DPG) were well-maintained in heparinized blood when it was acidified and pHe and pHi at 4degrees were both about 7.4, which suggests that improvement of blood preservation may be attained by suitable adjustment of the pHi and pHe of the blood."}
{"id": "PMID:5408", "title": "Purification and properties of two ribonucleases in different intracellular compartments in pea root tissue.", "content": "Two RNases in bound forms associated with the microsomal membrane and with the ribosomes or unknown particles in pea root tissue were solubilized by subjecting the membrane to sonic oscillation in the presence of EDTA and KC1 and by treating the particles with EDTA, respectively. The RNases were than purified by DEAE-cellulose and Sephadex G-75 column chromatographies. The elution profiles of RNases from the columns were very similar. No significant differences were observed in their electrophoretic mobilities in polyacrylamide gels, in molecular weight, in activation by inorganic ions, urea or phospholipid micelles or in the dependence of their activities upon pH. The purified RNASES were not different from the bound enzymes as regards activation by inorganic ions and urea and the dependence of the activity upon pH. Triton X-100 stimulated the activity only if RNase was in a bound form associated with the microsomal membrane. We propose that the two RNases may be the same molecular species and differ only in the form of association with intracellular structures.", "contents": "Purification and properties of two ribonucleases in different intracellular compartments in pea root tissue. Two RNases in bound forms associated with the microsomal membrane and with the ribosomes or unknown particles in pea root tissue were solubilized by subjecting the membrane to sonic oscillation in the presence of EDTA and KC1 and by treating the particles with EDTA, respectively. The RNases were than purified by DEAE-cellulose and Sephadex G-75 column chromatographies. The elution profiles of RNases from the columns were very similar. No significant differences were observed in their electrophoretic mobilities in polyacrylamide gels, in molecular weight, in activation by inorganic ions, urea or phospholipid micelles or in the dependence of their activities upon pH. The purified RNASES were not different from the bound enzymes as regards activation by inorganic ions and urea and the dependence of the activity upon pH. Triton X-100 stimulated the activity only if RNase was in a bound form associated with the microsomal membrane. We propose that the two RNases may be the same molecular species and differ only in the form of association with intracellular structures."}
{"id": "PMID:5409", "title": "Purification and properties of an exo-cellulase component of novel type from Trichoderma miride.", "content": "An enzyme extract from Cellulase-Onozuka, a commercial product of Trichoderma viride, was fractionated by Amberlite CG-50 column chromatography into three cellulase [EC 3.2.1.4] groups, peaks I to III. A noval enzyme, which has both beta-glucosidase [EC 3.2.1.21] and exo-carboxymethyl-cellulase (exo-CMCase) properties was obtained from peak III by extensive purification throuh consecutive column chromatography. The enzyme was homogeneous on ultracentrifugation, SDS-gel and cellulose acetate film electrophoreses and molecular sieve chromatography on Bio-Gel P-150. The molecular weight of this enzyme was estimated to be 53,000. The enzyme appeared to release cellobiose residues one by one from the nonreducing end of higher cellooligosaccharides and CM-cellulose (CMC), but to release glucosyl residues from reduced cellotriose and beta-cellobioside, resembling a beta-glucosidase in this respect. Furthermore, this exo-CMCase also attacked xylan exo-wise to produce xylobiose moleculaes one by one, but it scarcely attacked insoluble cellulose, except for a cellodextrin apparently rich in amorphous structure.", "contents": "Purification and properties of an exo-cellulase component of novel type from Trichoderma miride. An enzyme extract from Cellulase-Onozuka, a commercial product of Trichoderma viride, was fractionated by Amberlite CG-50 column chromatography into three cellulase [EC 3.2.1.4] groups, peaks I to III. A noval enzyme, which has both beta-glucosidase [EC 3.2.1.21] and exo-carboxymethyl-cellulase (exo-CMCase) properties was obtained from peak III by extensive purification throuh consecutive column chromatography. The enzyme was homogeneous on ultracentrifugation, SDS-gel and cellulose acetate film electrophoreses and molecular sieve chromatography on Bio-Gel P-150. The molecular weight of this enzyme was estimated to be 53,000. The enzyme appeared to release cellobiose residues one by one from the nonreducing end of higher cellooligosaccharides and CM-cellulose (CMC), but to release glucosyl residues from reduced cellotriose and beta-cellobioside, resembling a beta-glucosidase in this respect. Furthermore, this exo-CMCase also attacked xylan exo-wise to produce xylobiose moleculaes one by one, but it scarcely attacked insoluble cellulose, except for a cellodextrin apparently rich in amorphous structure."}
{"id": "PMID:5410", "title": "Studies on D-tetrose metabolism. VI. Crystallization and some properties of D-erythrulose reducatase from beef liver.", "content": "D-Erythrulose reductase of beef liver was crystallized from ammonium sulfate solution at pH 8.17. The crystals are needle-shaped. The enzyme protein contains 851 amino acid residues per mole of the enzyme: Lys28, His11, Arg52, Asp79, Thr58, Ser56, Glu68, Pro20, Gly80, Ala107, Val112, Met24, Ile31, Leu88, Tyr7, Phe22, Trp4, and Cys4. The enzyme is inactivated by exposure to temperatures below 12degrees. The inactivation is accelerated by increasing the salt concentration and decreasing the enzyme concentration. The pH of the medium also has a pronounced effect, the maximum stability of the enzyme is obtained at pH 8.5. NADP+ protected the enzyme from cold inactivation at all stages of the process and also afforded protection against inactivation by heat and pH. The cold inactivation of the enzyme is accompanied by dissociation of the enzyme protein to subunits.", "contents": "Studies on D-tetrose metabolism. VI. Crystallization and some properties of D-erythrulose reducatase from beef liver. D-Erythrulose reductase of beef liver was crystallized from ammonium sulfate solution at pH 8.17. The crystals are needle-shaped. The enzyme protein contains 851 amino acid residues per mole of the enzyme: Lys28, His11, Arg52, Asp79, Thr58, Ser56, Glu68, Pro20, Gly80, Ala107, Val112, Met24, Ile31, Leu88, Tyr7, Phe22, Trp4, and Cys4. The enzyme is inactivated by exposure to temperatures below 12degrees. The inactivation is accelerated by increasing the salt concentration and decreasing the enzyme concentration. The pH of the medium also has a pronounced effect, the maximum stability of the enzyme is obtained at pH 8.5. NADP+ protected the enzyme from cold inactivation at all stages of the process and also afforded protection against inactivation by heat and pH. The cold inactivation of the enzyme is accompanied by dissociation of the enzyme protein to subunits."}
{"id": "PMID:5411", "title": "Studies on phospholipases from Streptomyces. III. Purification and properties of Streptomyces hachijoensis phospholipase C.", "content": "1. Phospholipase C [EC 3.1.4.3] found in the growth medium of Streptomyces hachijoensis was purified about sixty-fold by dialysis and column chromatography on Sephadex G-50. 2. The active fraction was separated by isoelectric focusing into two fractions, phospholipase C-I (pI 6.0) and phospholipase C-II (pI 5.6). 3. Both purified phospholipases C were homogeneous by immunodiffusion and were not differentiated as regards antigencity. 4. Phospholipase C-I had maximal activity at pH 8.0 and the optimal temperature was 50degree. Phospholipase C-I was stable at 50degrees for 30 min and was stable at neutral pH. 5. The activity of phospholipase C-I was inhibited by high concentrations of various detergents such as Triton X-100, sodium, cholate, SDS and was also inhibited by Ca2+, Ba2+, Al3+, and EDTA, but was stimulated by Mg2+, and ethyl ether. 6. The Km value of phospholipase C-I was 0.9 mM, using phosphatidylcholine as a substrate. 7. By the gel filtration procedure, the molecular weights of phospholipase C-I and -II were both determined to be 18,000. 8. Phosphatidylcholine, phosphatidylinositol, cardiolipin, sphingomyelin, and lysophosphatidylcholine were hydrolyzed by phospholipase C-I, but phosphatidylethanolamine and phosphatidylserine were hydrolyzed with difficulty under the same conditions, Phospholipase C-I also hydrolyzed phosphatidic acid.", "contents": "Studies on phospholipases from Streptomyces. III. Purification and properties of Streptomyces hachijoensis phospholipase C. 1. Phospholipase C [EC 3.1.4.3] found in the growth medium of Streptomyces hachijoensis was purified about sixty-fold by dialysis and column chromatography on Sephadex G-50. 2. The active fraction was separated by isoelectric focusing into two fractions, phospholipase C-I (pI 6.0) and phospholipase C-II (pI 5.6). 3. Both purified phospholipases C were homogeneous by immunodiffusion and were not differentiated as regards antigencity. 4. Phospholipase C-I had maximal activity at pH 8.0 and the optimal temperature was 50degree. Phospholipase C-I was stable at 50degrees for 30 min and was stable at neutral pH. 5. The activity of phospholipase C-I was inhibited by high concentrations of various detergents such as Triton X-100, sodium, cholate, SDS and was also inhibited by Ca2+, Ba2+, Al3+, and EDTA, but was stimulated by Mg2+, and ethyl ether. 6. The Km value of phospholipase C-I was 0.9 mM, using phosphatidylcholine as a substrate. 7. By the gel filtration procedure, the molecular weights of phospholipase C-I and -II were both determined to be 18,000. 8. Phosphatidylcholine, phosphatidylinositol, cardiolipin, sphingomyelin, and lysophosphatidylcholine were hydrolyzed by phospholipase C-I, but phosphatidylethanolamine and phosphatidylserine were hydrolyzed with difficulty under the same conditions, Phospholipase C-I also hydrolyzed phosphatidic acid."}
{"id": "PMID:5412", "title": "Thermal denaturation and regeneration of japanese-radish peroxidase.", "content": "Thermal denaturation of Japanese-radish peroxidase [EC 1.11.1.7] was investigated with respect to its spectrophotometric properties and effect on the enzymatic activity. Inactivation of the peroxidase occurred at temperatures higher than 60degrees and involved three processes, i.e., dissociation of protohemin from the holoperoxidase, a conformation change in the apperoxidase, and the modification or degradation of protohemin. The splitting process of protohemin from holoperoxidase as followed by the change in the absorption spectrum at high temperatures coincided with the degrease in the activity, and it was found to be at least biphasic. The regeneration of peroxidase on cooling to room temperature was essentially reversible at neutral pH, while at pH 5 and pH 9 these processes were irreversible. The irreversibility at acidic pH was mainly due to an irreversible change in the conformation of the apoenzyme. The difference spectrum of heat-treated apoperoxidase exhibited a denaturation blueshift with negative maxima at 287 and 294 nm, and the total protein fluorescence quantum yield. qprotein, increased by 20% compared to that of the untreated apoenzyme. On the other hand, the irreversibility at alkaline pH was largely attributable to the modification of protohemin. Apoperoxidase was more resistnat to heat denaturation but the modification or degradation of protohemin in heated enzyme was greater at alkaline pH than at acidic pH. The pyridine-ferrohemochrome spectrum of peroxidase exhibited slight shifts of the maxima of the alpha-band to shorter wavelength on heat treatment, and the paper chromatogram showed the presence of a new derivative other than protohemin. The modified product is probably (2(4)-vinyl-4(2)-hydroxyethyldeuterohemin.", "contents": "Thermal denaturation and regeneration of japanese-radish peroxidase. Thermal denaturation of Japanese-radish peroxidase [EC 1.11.1.7] was investigated with respect to its spectrophotometric properties and effect on the enzymatic activity. Inactivation of the peroxidase occurred at temperatures higher than 60degrees and involved three processes, i.e., dissociation of protohemin from the holoperoxidase, a conformation change in the apperoxidase, and the modification or degradation of protohemin. The splitting process of protohemin from holoperoxidase as followed by the change in the absorption spectrum at high temperatures coincided with the degrease in the activity, and it was found to be at least biphasic. The regeneration of peroxidase on cooling to room temperature was essentially reversible at neutral pH, while at pH 5 and pH 9 these processes were irreversible. The irreversibility at acidic pH was mainly due to an irreversible change in the conformation of the apoenzyme. The difference spectrum of heat-treated apoperoxidase exhibited a denaturation blueshift with negative maxima at 287 and 294 nm, and the total protein fluorescence quantum yield. qprotein, increased by 20% compared to that of the untreated apoenzyme. On the other hand, the irreversibility at alkaline pH was largely attributable to the modification of protohemin. Apoperoxidase was more resistnat to heat denaturation but the modification or degradation of protohemin in heated enzyme was greater at alkaline pH than at acidic pH. The pyridine-ferrohemochrome spectrum of peroxidase exhibited slight shifts of the maxima of the alpha-band to shorter wavelength on heat treatment, and the paper chromatogram showed the presence of a new derivative other than protohemin. The modified product is probably (2(4)-vinyl-4(2)-hydroxyethyldeuterohemin."}
{"id": "PMID:5413", "title": "pH dependence of the binding constants of N-acetylglucosamine monomers to hen and turkey egg-white lysozymes.", "content": "The binding constants of N-acetylglucosamine (G1cNAc) and its methyl alpha- and beta- glycosides to hen and turkey egg-white lysozymes [EC 3.2.1.17], in the latter of which Asp 101 is replaced by Gly, were determined at various pH values by measuring changes in the circular dichroic (DC) band at 295 nm. The binding of beta-methyl-G1cNAc to turkey and hen lysozymes perturbed the pK value of Glu 35 from 6.0 to 6.5, the pK value of Asp 52 from 3.5 to 3.9, and the pK value of Asp 66 from 1.3 to 0.7. In addition, perturbation of the pK value of Asp 101 from 4.4 to 4.0 was observed in the binding of this saccharide to hen lysozyme. The binding of alpha-methyl-GlcNAc to hen and turkey lysozymes perturbed the pK value of Glu 35 to the alkaline side by about 0.5 pH unit, the pK value of Asp 66 to the acidic side by about 0.5 pH unit, and the pK value (4.4) of an ionizable group to the acidic side by about 0.6 pH unit. The last ionizable group was tentatively assigned to Asp 48. The pK value of Asp 52 was not perturbed by the binding of this saccharide. The pH dependence curves for the binding of GlcNAc to hen and turkey lysozymes were very similar and it was suggested that Asp 48, in addition to Asp 66, Asp 52, and Glu 35, is perturbed by the binding of GlcNAc.", "contents": "pH dependence of the binding constants of N-acetylglucosamine monomers to hen and turkey egg-white lysozymes. The binding constants of N-acetylglucosamine (G1cNAc) and its methyl alpha- and beta- glycosides to hen and turkey egg-white lysozymes [EC 3.2.1.17], in the latter of which Asp 101 is replaced by Gly, were determined at various pH values by measuring changes in the circular dichroic (DC) band at 295 nm. The binding of beta-methyl-G1cNAc to turkey and hen lysozymes perturbed the pK value of Glu 35 from 6.0 to 6.5, the pK value of Asp 52 from 3.5 to 3.9, and the pK value of Asp 66 from 1.3 to 0.7. In addition, perturbation of the pK value of Asp 101 from 4.4 to 4.0 was observed in the binding of this saccharide to hen lysozyme. The binding of alpha-methyl-GlcNAc to hen and turkey lysozymes perturbed the pK value of Glu 35 to the alkaline side by about 0.5 pH unit, the pK value of Asp 66 to the acidic side by about 0.5 pH unit, and the pK value (4.4) of an ionizable group to the acidic side by about 0.6 pH unit. The last ionizable group was tentatively assigned to Asp 48. The pK value of Asp 52 was not perturbed by the binding of this saccharide. The pH dependence curves for the binding of GlcNAc to hen and turkey lysozymes were very similar and it was suggested that Asp 48, in addition to Asp 66, Asp 52, and Glu 35, is perturbed by the binding of GlcNAc."}
{"id": "PMID:5414", "title": "Elementary processes in the interaction of serine protease with a possible transition state analog. Subtillisin-benzeneboronic acid system.", "content": "The interaction of benzeneboronic acid(BBA), a possible transition state analog, with subtilisin BPN' [EC 3.4.21.14] was studied by the temperature-jump method at various pH's, temperatures and in D2O as well as H2O. From analysis of the concentration dependence of the relaxation times, it was suggested that the subtillsin-BBA interactions consist of at least two elementary steps, a fast bimolecular association followed by a slow unimolecular process. Similar concentration dependence was observed at pH 6.1-6.7 at 25degrees. However, in D2O the reciprocal relaxation times generally decreased compared to those in H2O and became concentration-independent below pD 6.5. The relaxation times were influenced considerably by the temperature. From these results, the slow unimolecular process was assigned to the trigonal-tetrahedral interconversion of BBA at the active site of the enzyme.", "contents": "Elementary processes in the interaction of serine protease with a possible transition state analog. Subtillisin-benzeneboronic acid system. The interaction of benzeneboronic acid(BBA), a possible transition state analog, with subtilisin BPN' [EC 3.4.21.14] was studied by the temperature-jump method at various pH's, temperatures and in D2O as well as H2O. From analysis of the concentration dependence of the relaxation times, it was suggested that the subtillsin-BBA interactions consist of at least two elementary steps, a fast bimolecular association followed by a slow unimolecular process. Similar concentration dependence was observed at pH 6.1-6.7 at 25degrees. However, in D2O the reciprocal relaxation times generally decreased compared to those in H2O and became concentration-independent below pD 6.5. The relaxation times were influenced considerably by the temperature. From these results, the slow unimolecular process was assigned to the trigonal-tetrahedral interconversion of BBA at the active site of the enzyme."}
{"id": "PMID:5415", "title": "Kinetic studies of carboxypeptidase Y. III. Action on ester, amide, and anilide substrates and the effects of some environmental factors.", "content": "Kinetic parameters of carboxypeptidase Y are given for the hydrolyses of ester, amide, and anilide substrates. The kcat/Km values were compatible with those of chymotrypsin [EC 3.4.21.1] with a few exceptions. One ionizable group with a pK of around 5.8 was suggested to be involved in the free enzyme in hydrolyzing all the substrates, including peptide substrates. In addition, hydroxylaminolysis and the kinetic isotope effects of deuterium oxide indicated, with some reservations, a reaction mechanism which proceeds via the formation of an acyl intermediate.", "contents": "Kinetic studies of carboxypeptidase Y. III. Action on ester, amide, and anilide substrates and the effects of some environmental factors. Kinetic parameters of carboxypeptidase Y are given for the hydrolyses of ester, amide, and anilide substrates. The kcat/Km values were compatible with those of chymotrypsin [EC 3.4.21.1] with a few exceptions. One ionizable group with a pK of around 5.8 was suggested to be involved in the free enzyme in hydrolyzing all the substrates, including peptide substrates. In addition, hydroxylaminolysis and the kinetic isotope effects of deuterium oxide indicated, with some reservations, a reaction mechanism which proceeds via the formation of an acyl intermediate."}
{"id": "PMID:5417", "title": "Developmental changes in the structure and kinetic properties of myosin adenosinetriphosphatase of rabbit skeletal fast muscle.", "content": "Structural and functional changes in myosin of fast muscles during early post-natal development were studied to seek correlations with well-known physiological changes in the contraction rate. The findings were as follows: 1. It is known that fetal fast muscle myosin contains three kinds of light chains. It was confirmed that their molecular weights were the same as those of adult fast muscle myosin, but different from those of adult slow muscle myosin. The amount of the smallest light chain, g3, was confirmed to increase markedly during the postnatal period. 2. The ATPase [EC3.6.1.3] activity of fetal fast muscle myosin (-1 day) was found to be about 50% of that of adult myosin. The pH-activity curve of fetal myosin ATPase was confirmed to be similar to that of adult myosin. 3. The rate of formation of the reactive myosin-phosphate-ADP complex, MADPP, was found not to change during post-natal development. 4. It was found that the rate of decomposition of MADPP in the presence of F-actin increased markedly during the post-natal period, and that the rate of decomposition of the complex of fetal mysoin was only 1/6 to 1/4 of that of adult myosin. The change in the actomyosin ATPase activity was found to be closely correlated with the increase in the g3 content during development.", "contents": "Developmental changes in the structure and kinetic properties of myosin adenosinetriphosphatase of rabbit skeletal fast muscle. Structural and functional changes in myosin of fast muscles during early post-natal development were studied to seek correlations with well-known physiological changes in the contraction rate. The findings were as follows: 1. It is known that fetal fast muscle myosin contains three kinds of light chains. It was confirmed that their molecular weights were the same as those of adult fast muscle myosin, but different from those of adult slow muscle myosin. The amount of the smallest light chain, g3, was confirmed to increase markedly during the postnatal period. 2. The ATPase [EC3.6.1.3] activity of fetal fast muscle myosin (-1 day) was found to be about 50% of that of adult myosin. The pH-activity curve of fetal myosin ATPase was confirmed to be similar to that of adult myosin. 3. The rate of formation of the reactive myosin-phosphate-ADP complex, MADPP, was found not to change during post-natal development. 4. It was found that the rate of decomposition of MADPP in the presence of F-actin increased markedly during the post-natal period, and that the rate of decomposition of the complex of fetal mysoin was only 1/6 to 1/4 of that of adult myosin. The change in the actomyosin ATPase activity was found to be closely correlated with the increase in the g3 content during development."}
{"id": "PMID:5418", "title": "Control of rabbit liver fructose-1, 6-diphosphatase activity by magnesium ions.", "content": "EDTA at a concentration of 1 muM produced a threshold effect in the activation of purified rabbit liver fructose-1, 6-diphosphatase [EC 3.1.3.11] in the presence of 5 mM Mg2+ at pH 7.2. Without EDTA, biphasic activation curves were produced by Mg2+. A double-reciprocal plot of the data gave the Km values corresponding to the two linear regions. They were 0.19 and 0.83 mM at pH 7.5, and 0.055 and 0.83 mM at pH 9.1. In the presence of 5muM EDTA a sigmoidal curve was obtained for Mg2+ activation in the range of noninhibitory Mg2+ concentrations at pH 7.2. The apparent Km value for Mg2+ was 0.15 mM, and the Hill coefficient was 2.0. At pH 9.1 cooperativity among the Mg2+ sites disappeared, and the apparent Km value for Mg2+ was 0.055 mM. These Km values at pH 7.2 or 9.1 corresponded to the smaller of the biphasic Km values obtained without EDTA. In the absence of EDTA, no inhibition by Mg2+ was observed in the Mg2+ concentration range below 10 mM. In the presence of EDTA, the enzyme was inhibited markedly by Mg2+ at concentrations above 0.5 mM at pH 7.2, and was more sensitive to inhibition at pH 9.1. The effects of pH on the Km value for Mg2+ activation and on the Mg2+ inhibition contributed to an apparent shift of the pH optimum for activity induced by EDTA. Cooperative interaction among fructose-1, 6-diphosphate sites was observed for the enzyme in the presence of EDTA. The Hill coefficient was approximatley 1.8, and the apparent Km value for the substrate was 0.74 muM. EDTA appears to make liver fructose-1, 6-diphosphatase very sensitive to various effectors. It is suggested that Mg2+ serves as a regulator for the enzyme activity.", "contents": "Control of rabbit liver fructose-1, 6-diphosphatase activity by magnesium ions. EDTA at a concentration of 1 muM produced a threshold effect in the activation of purified rabbit liver fructose-1, 6-diphosphatase [EC 3.1.3.11] in the presence of 5 mM Mg2+ at pH 7.2. Without EDTA, biphasic activation curves were produced by Mg2+. A double-reciprocal plot of the data gave the Km values corresponding to the two linear regions. They were 0.19 and 0.83 mM at pH 7.5, and 0.055 and 0.83 mM at pH 9.1. In the presence of 5muM EDTA a sigmoidal curve was obtained for Mg2+ activation in the range of noninhibitory Mg2+ concentrations at pH 7.2. The apparent Km value for Mg2+ was 0.15 mM, and the Hill coefficient was 2.0. At pH 9.1 cooperativity among the Mg2+ sites disappeared, and the apparent Km value for Mg2+ was 0.055 mM. These Km values at pH 7.2 or 9.1 corresponded to the smaller of the biphasic Km values obtained without EDTA. In the absence of EDTA, no inhibition by Mg2+ was observed in the Mg2+ concentration range below 10 mM. In the presence of EDTA, the enzyme was inhibited markedly by Mg2+ at concentrations above 0.5 mM at pH 7.2, and was more sensitive to inhibition at pH 9.1. The effects of pH on the Km value for Mg2+ activation and on the Mg2+ inhibition contributed to an apparent shift of the pH optimum for activity induced by EDTA. Cooperative interaction among fructose-1, 6-diphosphate sites was observed for the enzyme in the presence of EDTA. The Hill coefficient was approximatley 1.8, and the apparent Km value for the substrate was 0.74 muM. EDTA appears to make liver fructose-1, 6-diphosphatase very sensitive to various effectors. It is suggested that Mg2+ serves as a regulator for the enzyme activity."}
{"id": "PMID:5419", "title": "Two molecular forms of thymidine kinase in the cytosol of regenerating rat liver.", "content": "Two forms (Peak A and Peak B) of thymidine kinase [EC 2.7.1.75] from regenerating rat liver cytosol were resolved and partially purified by Deae-cellulose chromatography. Both fractions were identical with respect to their substrate requirement, pH optima, metal requirements, and molecular weight, as judged by their sedimentation in sucrose density gradient centrifugation. Peak B differed from Peak A in heat sensitivity, inhibition by dCTP and Km for thymidine and ATP. Peak B enzyme was the only enzyme found in normal adult liver and Peak A enzyme was the form increasing predominantly in regenerating liver.", "contents": "Two molecular forms of thymidine kinase in the cytosol of regenerating rat liver. Two forms (Peak A and Peak B) of thymidine kinase [EC 2.7.1.75] from regenerating rat liver cytosol were resolved and partially purified by Deae-cellulose chromatography. Both fractions were identical with respect to their substrate requirement, pH optima, metal requirements, and molecular weight, as judged by their sedimentation in sucrose density gradient centrifugation. Peak B differed from Peak A in heat sensitivity, inhibition by dCTP and Km for thymidine and ATP. Peak B enzyme was the only enzyme found in normal adult liver and Peak A enzyme was the form increasing predominantly in regenerating liver."}
{"id": "PMID:5420", "title": "The modification of sulfhydryl groups of glutamine synthetase from Bacillus stearothermophilus with 5, 5'-dithiobis(2-nitrobenzoic acid).", "content": "The SH groups of glutamine synthetase [EC 6.3.1.2] from Bacillus stearothermophilus were modified with 5, 5'-dithiobis(2-nitrobenzoic acid) in order to determine the number of SH groups in the molecule  as well as the effect of the modification on the enzyme activity. Three SH groups per subunit were detected after complete denaturation of the enzyme with 6 M urea, one of which was essential for the enzyme activity in view of its reactivity with 5, 5'-dithiobis(2-nitrobenzoic acid) on addition of MgCl2 with loss of the activity. The CD spectra of the modified enzyme in the near ultraviolet region changed from that of the native enzyme, indicating that aromatic amino acid residues were affected by modification of the SH group. The fluorescence derived from tryptophanyl residue(s) was quenched depending on the extent of modification of the SH group, suggesting that the tryptophanyl residue(s) was located in the proximity of the SH group. The thermostability of the enzyme was remarkably decreased by modification of the SH group.", "contents": "The modification of sulfhydryl groups of glutamine synthetase from Bacillus stearothermophilus with 5, 5'-dithiobis(2-nitrobenzoic acid). The SH groups of glutamine synthetase [EC 6.3.1.2] from Bacillus stearothermophilus were modified with 5, 5'-dithiobis(2-nitrobenzoic acid) in order to determine the number of SH groups in the molecule  as well as the effect of the modification on the enzyme activity. Three SH groups per subunit were detected after complete denaturation of the enzyme with 6 M urea, one of which was essential for the enzyme activity in view of its reactivity with 5, 5'-dithiobis(2-nitrobenzoic acid) on addition of MgCl2 with loss of the activity. The CD spectra of the modified enzyme in the near ultraviolet region changed from that of the native enzyme, indicating that aromatic amino acid residues were affected by modification of the SH group. The fluorescence derived from tryptophanyl residue(s) was quenched depending on the extent of modification of the SH group, suggesting that the tryptophanyl residue(s) was located in the proximity of the SH group. The thermostability of the enzyme was remarkably decreased by modification of the SH group."}
{"id": "PMID:5421", "title": "Titration study of acetylated lysozyme.", "content": "To study the interaction between carboxyl groups and amino groups in native lysozyme [EC 3.2.1.17], and to identify the positions and the pK values of the abnormal carboxyl groups, N-acetylated lysozyme was prepared. The acetylation did not affect the molecular shape of the enzyme, but changed six amino groups to a non-ionizable form, leaving one amino group free; this was determined to be Lys 33. In addition, pH titration of the acetylated lysozyme in 0.2 or 0.02 M KCl aqueous solution indicated fewer titratable groups with pK(int) of 7.8 or 10.4 compared with the native protein, though the number of titratable carboxyl groups was not affected by the acetylation. From the pH titration results and structural considerations, the unititratable carboxyl groups were suggested to be Asp 48, Asp 66, and Asp 87. On the other hand, spectrophotometric titration in 0.2 M KCl showed that all three tyrosine residues are titratable in the acetylated protein, although an abnormal tyrosine residue exists in the native state. Tyr 20 was suggested to be untitratable in the pH range of 8-12.6.", "contents": "Titration study of acetylated lysozyme. To study the interaction between carboxyl groups and amino groups in native lysozyme [EC 3.2.1.17], and to identify the positions and the pK values of the abnormal carboxyl groups, N-acetylated lysozyme was prepared. The acetylation did not affect the molecular shape of the enzyme, but changed six amino groups to a non-ionizable form, leaving one amino group free; this was determined to be Lys 33. In addition, pH titration of the acetylated lysozyme in 0.2 or 0.02 M KCl aqueous solution indicated fewer titratable groups with pK(int) of 7.8 or 10.4 compared with the native protein, though the number of titratable carboxyl groups was not affected by the acetylation. From the pH titration results and structural considerations, the unititratable carboxyl groups were suggested to be Asp 48, Asp 66, and Asp 87. On the other hand, spectrophotometric titration in 0.2 M KCl showed that all three tyrosine residues are titratable in the acetylated protein, although an abnormal tyrosine residue exists in the native state. Tyr 20 was suggested to be untitratable in the pH range of 8-12.6."}
{"id": "PMID:5422", "title": "Isolation of a low molecular weight active fragment of potato proteinase inhibitor IIb.", "content": "A low molecular weight active fragment of potato proteinase inhibitor IIPB was obtained by incubating the inhibitor with an equimolar amount of trypsin [EC 3.4.21.4] at pH 8 and 30 degrees for 16 hr, followed by gel filtration through Sephadex G-50, treatment with trichloroacetic acid, and CM-cellulose chromatography. The purified active fragment consisted of a single peptide chain with a molecular weight of 4,300, comprising 39 amino acid residues. It retained very strong inhibitory activity against chymotrypsin [EC 3.4.21.1] and subtilisin [EC 3.4.21.14]. However, the yield of this active fragment was rather low and was variable. On further incubation with trypsin, it was converted into smaller inactive peptides.", "contents": "Isolation of a low molecular weight active fragment of potato proteinase inhibitor IIb. A low molecular weight active fragment of potato proteinase inhibitor IIPB was obtained by incubating the inhibitor with an equimolar amount of trypsin [EC 3.4.21.4] at pH 8 and 30 degrees for 16 hr, followed by gel filtration through Sephadex G-50, treatment with trichloroacetic acid, and CM-cellulose chromatography. The purified active fragment consisted of a single peptide chain with a molecular weight of 4,300, comprising 39 amino acid residues. It retained very strong inhibitory activity against chymotrypsin [EC 3.4.21.1] and subtilisin [EC 3.4.21.14]. However, the yield of this active fragment was rather low and was variable. On further incubation with trypsin, it was converted into smaller inactive peptides."}
{"id": "PMID:5423", "title": "Isolation and characterization of a proteinase from the sarcocarp of melon fruit.", "content": "A proteinase from the sarcocarp of melon (Cucumis Melo L. var. Prince) was purified by a three-step procedure involving batch-wise treatment with CM-cellulose fibers, column chromatography on CM-cellulose powder and gel filtration on Sephadex G-75. The final enzyme preparation was homogeneous on acrylamide gel electrophoresis. Its molecular weight was estimated by two different methods to be about 50,000. Anlayses indicated tha presence of 475 amino acid residues and at least 7 moles of hexose. The maximum activity was found in the alkaline pH region against casein as a substrate. The optimum temperature against casein was 70 degrees at pH 7.1. The enzyme was strongly inhibited by diisopropyl fluorophosphate, partly inhibited by HgCl2 and not inhibited by EDTA, p-chloromercuribenzoic acid, N-tosyl-L-lysine chloromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone, and soybean trypsin inhibitor. The reduced and carboxymethylated insulin B-chain was cleaved at the peptide bonds of Asn3-Gln4, Cm-Cys7-Gly8, Glu13-Ala14, Leu15-Tyr16, Cm-Cys19-Gly20, Phe25-Tyr26, Pro28-Lys29, and Lys29-Ala30 by the enzyme.", "contents": "Isolation and characterization of a proteinase from the sarcocarp of melon fruit. A proteinase from the sarcocarp of melon (Cucumis Melo L. var. Prince) was purified by a three-step procedure involving batch-wise treatment with CM-cellulose fibers, column chromatography on CM-cellulose powder and gel filtration on Sephadex G-75. The final enzyme preparation was homogeneous on acrylamide gel electrophoresis. Its molecular weight was estimated by two different methods to be about 50,000. Anlayses indicated tha presence of 475 amino acid residues and at least 7 moles of hexose. The maximum activity was found in the alkaline pH region against casein as a substrate. The optimum temperature against casein was 70 degrees at pH 7.1. The enzyme was strongly inhibited by diisopropyl fluorophosphate, partly inhibited by HgCl2 and not inhibited by EDTA, p-chloromercuribenzoic acid, N-tosyl-L-lysine chloromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone, and soybean trypsin inhibitor. The reduced and carboxymethylated insulin B-chain was cleaved at the peptide bonds of Asn3-Gln4, Cm-Cys7-Gly8, Glu13-Ala14, Leu15-Tyr16, Cm-Cys19-Gly20, Phe25-Tyr26, Pro28-Lys29, and Lys29-Ala30 by the enzyme."}
{"id": "PMID:5424", "title": "D-alpha-Hydroxyglutarate dehydrogenase of Rhodospirillum rubrum.", "content": "D-alpha-Hydroxyglutarate dehydrogenase of R. rubrum grown anaerobically in the light was partially purified and some properties were investigated. 1. The enzyme catalyze stoichiometrically the dehydrogenation reaction of D-alpha-hydroxyglutarate into alpha-oxoglutarate, coupled with the reduction of 2, 6-dichlorophenolindophenol. 2. Cytochrome c2, cytochrome c, and ferricyanide are effective as electron acceptors with the crude enzyme but not with the purified one, whereas NAD+ and NADP+ are completely ineffective. The enzyme is thought to play a role in the electron transport system of the organism. 3. D-alpha-Hydroxyglutarate is virtually the sole substrate for the enzyme. The apparent activity against L-alpha-hydroxyglutarate is presumed to be due to contamination of the L-isomer sample with the D-isomer. The enzyme shows barely detectable activity against both isomers of malate and virtually no activity against DL-lactate and glycolate. 4. Both isomers of malate and oxalate, which are presumably substrate analogues, inhibit the enzyme activity. 5. The enzyme is not an inducible enzyme but rather is a constitutive one for R. rubrum, unlike from the enzyme of Pseudomonas putida which is an inducible enzyme for the catabolism of lysine.", "contents": "D-alpha-Hydroxyglutarate dehydrogenase of Rhodospirillum rubrum. D-alpha-Hydroxyglutarate dehydrogenase of R. rubrum grown anaerobically in the light was partially purified and some properties were investigated. 1. The enzyme catalyze stoichiometrically the dehydrogenation reaction of D-alpha-hydroxyglutarate into alpha-oxoglutarate, coupled with the reduction of 2, 6-dichlorophenolindophenol. 2. Cytochrome c2, cytochrome c, and ferricyanide are effective as electron acceptors with the crude enzyme but not with the purified one, whereas NAD+ and NADP+ are completely ineffective. The enzyme is thought to play a role in the electron transport system of the organism. 3. D-alpha-Hydroxyglutarate is virtually the sole substrate for the enzyme. The apparent activity against L-alpha-hydroxyglutarate is presumed to be due to contamination of the L-isomer sample with the D-isomer. The enzyme shows barely detectable activity against both isomers of malate and virtually no activity against DL-lactate and glycolate. 4. Both isomers of malate and oxalate, which are presumably substrate analogues, inhibit the enzyme activity. 5. The enzyme is not an inducible enzyme but rather is a constitutive one for R. rubrum, unlike from the enzyme of Pseudomonas putida which is an inducible enzyme for the catabolism of lysine."}
{"id": "PMID:5425", "title": "Effects of pH indicators on various activities of chromatophroes of Rhodospirillum rubrum.", "content": "1. The effects of pH indicators on activities for ATP hydrolysis in the dark and ATP-Pi exchange in the dark were examined with chromatophores from Rhodospirillum rubrum. Of thirty-one pH indicators tested, eleven (metanil yellow, 2, 4-dinitrophenol, ethyl orange, bromocresol green, resazurin, neutral red, bromthymol blue, alpha-naphtholphthalein, o-cresolphthalein, phenolphthalein, and alizarin yellow G) almost completely inhibited the activities for ATP formation and ATP-Pi exchange at concentrations of 1 mM, and were studied in detail. 2. Of the eleven pH indicators, those other than alpha-naptholphthalein, o-cresolphthalein and phenolphthalein, when assayed at appropriate concentrations, inhibited ATP-Pi exchange, but not ATP hydrolysis. In ATP-Pi exchange, these eight pH indicators at the concentrations described above were competitive against Pi, and non-competitive against ATP. The remaining three kinds of pH indicators were non-competitive against either Pi or ATP, when assayed at concentrations of the dyes that inhibited both activities. 3. The amounts of pH indicators bound with chromatophores were measured. No correlation was found between the amounts of the bound dyes and the extents of their inhibition of either ATP formation or ATP-Pi exchange. 4. Ethyl orange (pKa=4.1) and 2, 4-dinitrophenol (pKa=3.9) stimulated ATP hydrolysis to the greatest extent. The latter dye was hardly bound with chromatophores. 5. The stimulatory effects of pH indicators on ATP hydrolysis were hardly affected by extraction of quinones from chromatophores. 6. Most of the pH indicators stimulated both succinate-cytochrome c2 and NADH-cytochrome c2 reductions in the dark. 7. The mechanism of uncoupling of the electron transfer system and the phosphorylation system by pH indicators and the mechanism of the coupling are discussed.", "contents": "Effects of pH indicators on various activities of chromatophroes of Rhodospirillum rubrum. 1. The effects of pH indicators on activities for ATP hydrolysis in the dark and ATP-Pi exchange in the dark were examined with chromatophores from Rhodospirillum rubrum. Of thirty-one pH indicators tested, eleven (metanil yellow, 2, 4-dinitrophenol, ethyl orange, bromocresol green, resazurin, neutral red, bromthymol blue, alpha-naphtholphthalein, o-cresolphthalein, phenolphthalein, and alizarin yellow G) almost completely inhibited the activities for ATP formation and ATP-Pi exchange at concentrations of 1 mM, and were studied in detail. 2. Of the eleven pH indicators, those other than alpha-naptholphthalein, o-cresolphthalein and phenolphthalein, when assayed at appropriate concentrations, inhibited ATP-Pi exchange, but not ATP hydrolysis. In ATP-Pi exchange, these eight pH indicators at the concentrations described above were competitive against Pi, and non-competitive against ATP. The remaining three kinds of pH indicators were non-competitive against either Pi or ATP, when assayed at concentrations of the dyes that inhibited both activities. 3. The amounts of pH indicators bound with chromatophores were measured. No correlation was found between the amounts of the bound dyes and the extents of their inhibition of either ATP formation or ATP-Pi exchange. 4. Ethyl orange (pKa=4.1) and 2, 4-dinitrophenol (pKa=3.9) stimulated ATP hydrolysis to the greatest extent. The latter dye was hardly bound with chromatophores. 5. The stimulatory effects of pH indicators on ATP hydrolysis were hardly affected by extraction of quinones from chromatophores. 6. Most of the pH indicators stimulated both succinate-cytochrome c2 and NADH-cytochrome c2 reductions in the dark. 7. The mechanism of uncoupling of the electron transfer system and the phosphorylation system by pH indicators and the mechanism of the coupling are discussed."}
{"id": "PMID:5426", "title": "Binding of substrate analogues to subsites D, E, and F of hen egg-white lysozyme.", "content": "The pH dependence of the binding of dye, Beibrich Scarlet, to hen egg-white lysozyme[EC 3.2.1.17] was studied at ionic strength 0.3 and 25 degrees by following circular dichroic (CD)bands originating from the bound dye. This binding involved one of the catalytic groups, Glu 35. The effect of the binding of N-acetylglucosamine (GlcNAc), its dimer or trimer on the binding of this dye was also studied at pH 7.5 by measuring changes in the CD bands of the dye bound to lysozyme. It was shown that there are two sites for simultaneous binding of these saccharides in the lysozyme molecule. The stronger binding of the saccharide was noncompetitive and the weaker binding was competitive with dye binding. The binding constants for the stronger binding site (the upper portion of lysozyme cleft) were in good agreement with those previously determined by following changes in the tryptophyl CD bands of lysozyme. The binding constants to the weaker site were about 1.1 x 10(-4), 5 x 10(2), and 5M(-1) for the trimer, dimer, and monomer of GlcNAc, respectively. Assuming that the trimer, dimer, and monomer occupy subsites D, E, and F; E and F; and E, respectively, the unitary free energies of saccharide binding were estimated to be about --1.9, --3.3, and --2.7 kcal/mole for D, E, and F, respectively.", "contents": "Binding of substrate analogues to subsites D, E, and F of hen egg-white lysozyme. The pH dependence of the binding of dye, Beibrich Scarlet, to hen egg-white lysozyme[EC 3.2.1.17] was studied at ionic strength 0.3 and 25 degrees by following circular dichroic (CD)bands originating from the bound dye. This binding involved one of the catalytic groups, Glu 35. The effect of the binding of N-acetylglucosamine (GlcNAc), its dimer or trimer on the binding of this dye was also studied at pH 7.5 by measuring changes in the CD bands of the dye bound to lysozyme. It was shown that there are two sites for simultaneous binding of these saccharides in the lysozyme molecule. The stronger binding of the saccharide was noncompetitive and the weaker binding was competitive with dye binding. The binding constants for the stronger binding site (the upper portion of lysozyme cleft) were in good agreement with those previously determined by following changes in the tryptophyl CD bands of lysozyme. The binding constants to the weaker site were about 1.1 x 10(-4), 5 x 10(2), and 5M(-1) for the trimer, dimer, and monomer of GlcNAc, respectively. Assuming that the trimer, dimer, and monomer occupy subsites D, E, and F; E and F; and E, respectively, the unitary free energies of saccharide binding were estimated to be about --1.9, --3.3, and --2.7 kcal/mole for D, E, and F, respectively."}
{"id": "PMID:5427", "title": "Purification and characterization of alkaline phosphatase from rat kidney.", "content": "Alkaline phosphatase [EC 3.1.3.1.] was purified about 250-fold from rat kidney, and its enzymological properties were studied. Kidney homogenate was extracted with n-butanol, passed through Sephadex G-200 and chromatographed on a DEAE-cellulose column. The peak from the DEAE-cellulose column was subjected to isoelectric focusing, and the alkaline phosphatase activity was separated into two peaks. The molecular weights of alkaline phosphatase in these peaks were 4.8.X10(4) and 1.0X10(5), as determined by SDS-polyacrylamide gel electrophoresis. Anti-serum against alkaline phosphatase from rat kidney was prepared, and was shown to neutralize the activity from kidney, liver or bone, but not that from intestine.", "contents": "Purification and characterization of alkaline phosphatase from rat kidney. Alkaline phosphatase [EC 3.1.3.1.] was purified about 250-fold from rat kidney, and its enzymological properties were studied. Kidney homogenate was extracted with n-butanol, passed through Sephadex G-200 and chromatographed on a DEAE-cellulose column. The peak from the DEAE-cellulose column was subjected to isoelectric focusing, and the alkaline phosphatase activity was separated into two peaks. The molecular weights of alkaline phosphatase in these peaks were 4.8.X10(4) and 1.0X10(5), as determined by SDS-polyacrylamide gel electrophoresis. Anti-serum against alkaline phosphatase from rat kidney was prepared, and was shown to neutralize the activity from kidney, liver or bone, but not that from intestine."}
{"id": "PMID:5428", "title": "Studies on a microchemical method for the determination of the degree of polymerization of neutral oligo- and polysaccharides. I. Quantitative separation of trace amounts of alditols from mixtures with a large excess of monosaccharides.", "content": "A method has been devised for the quantitative separation of trace amounts of alditols from mixtures with large amounts of monosaccharides, using a strongly basic ion-exchange resin. Ten kinds of common reducing monosaccharides used were strongly retained by a very basic anion-exchange resin in the hydroxyl form, whereas the corresponding alditols showed no significant affinity for the basic resin. Model studies showed excellent recoveries of alditol from known mixtures of alditol and the corresponding aldose at ratios in the range from 1 : 1X10(3) TO 1 : 1X10(4) (by weight). Application of this procedure to dextrans after reduction and hydrolysis resulted in quantitative separation of the terminal alditol.", "contents": "Studies on a microchemical method for the determination of the degree of polymerization of neutral oligo- and polysaccharides. I. Quantitative separation of trace amounts of alditols from mixtures with a large excess of monosaccharides. A method has been devised for the quantitative separation of trace amounts of alditols from mixtures with large amounts of monosaccharides, using a strongly basic ion-exchange resin. Ten kinds of common reducing monosaccharides used were strongly retained by a very basic anion-exchange resin in the hydroxyl form, whereas the corresponding alditols showed no significant affinity for the basic resin. Model studies showed excellent recoveries of alditol from known mixtures of alditol and the corresponding aldose at ratios in the range from 1 : 1X10(3) TO 1 : 1X10(4) (by weight). Application of this procedure to dextrans after reduction and hydrolysis resulted in quantitative separation of the terminal alditol."}
{"id": "PMID:5429", "title": "Studies on barley trypsin inhibitor. II. Structural changes induced by denaturants and their reversibility.", "content": "No change in the activity of a trypsin inhibitor from barley was observed on treatment with heat and denaturants such as urea and guanidine hydrochloride. Thus, the conformational properties of the inhibitor were investigated. CD spectra of the native inhibitor were analysed on a curve-fitting technique using the data for poly-L-lysine...", "contents": "Studies on barley trypsin inhibitor. II. Structural changes induced by denaturants and their reversibility. No change in the activity of a trypsin inhibitor from barley was observed on treatment with heat and denaturants such as urea and guanidine hydrochloride. Thus, the conformational properties of the inhibitor were investigated. CD spectra of the native inhibitor were analysed on a curve-fitting technique using the data for poly-L-lysine..."}
{"id": "PMID:5430", "title": "Isolation and some properties of NAD+ reductase of the green photosynthetic bacterium Prosthecochloris aestuarii.", "content": "NAD+ reductase of the green photosynthetic bacterium Prosthecochloris aestuarii was isolated and purified by ammonium sulfate fractionation, DEAE-cellulose column chromatography, and Sephadex G-200 gel filtration. This enzyme is an FAD-containing flavoprotein and has absorption maxima at 485 (shoulder0 452, 411, and 385 nm (the 411 nm band is due to cytochrome). The molecular weight of the enzyme as determined by gel filtration using Sephadex G-200 is 119,000. The enzyme catalyzes the reduction of NAD+ and NADP+ by photoreduced spinach ferredoxin or reduced benzyl viologen...", "contents": "Isolation and some properties of NAD+ reductase of the green photosynthetic bacterium Prosthecochloris aestuarii. NAD+ reductase of the green photosynthetic bacterium Prosthecochloris aestuarii was isolated and purified by ammonium sulfate fractionation, DEAE-cellulose column chromatography, and Sephadex G-200 gel filtration. This enzyme is an FAD-containing flavoprotein and has absorption maxima at 485 (shoulder0 452, 411, and 385 nm (the 411 nm band is due to cytochrome). The molecular weight of the enzyme as determined by gel filtration using Sephadex G-200 is 119,000. The enzyme catalyzes the reduction of NAD+ and NADP+ by photoreduced spinach ferredoxin or reduced benzyl viologen..."}
{"id": "PMID:5431", "title": "Interaction of cyclodextrins with fluorescent probes and its application to kinetic studies of amylase.", "content": "It was found that 6-p-toluidinylnaphthalene-2-sulfonate (TNS) showed pronounced fluorescence enhancement when it was added to alpha-, beta-, and gamma-cyclodextrin solutions. 2. The following results were obtained by quantitative study of the interactions of three kinds of cyclodextrins with TNS by following TNS fluorescence at pH5.3. and 25 degrees. i) alpha-Cyclodextrin forms a l : l complex with TNS. ii) beta- and gamma-Cyclodextrins form 1 : 1 and also 2 : 1 complexes; in the latter two cyclodextrin molecules bind to one TNS molecule. iii) The dissociation constants of cyclodextrin-TNS complexes were determined to be 54.9 mM for alpha-cyclodextrin, 0.65 mM for beta-cyclodextrin and 0.66 mM for gamma-cyclodextrin in the 1 : 1 complex, and the secondary dissociation constants in the 2 : 1 complex were 71.4 mM for beta-cyclodextrin in the 1 : 1 complex, and the secondary dissociation constants in the 2 : 1 complex were 71.4 mM for beta-cyclodextrin and 32.6 mM for gamma-cyclodextrin. iv)...", "contents": "Interaction of cyclodextrins with fluorescent probes and its application to kinetic studies of amylase. It was found that 6-p-toluidinylnaphthalene-2-sulfonate (TNS) showed pronounced fluorescence enhancement when it was added to alpha-, beta-, and gamma-cyclodextrin solutions. 2. The following results were obtained by quantitative study of the interactions of three kinds of cyclodextrins with TNS by following TNS fluorescence at pH5.3. and 25 degrees. i) alpha-Cyclodextrin forms a l : l complex with TNS. ii) beta- and gamma-Cyclodextrins form 1 : 1 and also 2 : 1 complexes; in the latter two cyclodextrin molecules bind to one TNS molecule. iii) The dissociation constants of cyclodextrin-TNS complexes were determined to be 54.9 mM for alpha-cyclodextrin, 0.65 mM for beta-cyclodextrin and 0.66 mM for gamma-cyclodextrin in the 1 : 1 complex, and the secondary dissociation constants in the 2 : 1 complex were 71.4 mM for beta-cyclodextrin in the 1 : 1 complex, and the secondary dissociation constants in the 2 : 1 complex were 71.4 mM for beta-cyclodextrin and 32.6 mM for gamma-cyclodextrin. iv)..."}
{"id": "PMID:5432", "title": "Fluorine-19 as a covalent active site-directed magnetic resonance probe in aspartate transaminase.", "content": "Phosphypyridoxyl trifluoroethylamine has been synthesized as an active site-directed 19F NMR probe for aspartate transaminase. This coenzyme derivative adds stoichiometrically to the apotransaminase as observed by both fluorescence and circular dichroism measurements. The fluorinated phosphypyridoxamine derivative, when bound to the apotransaminase, will not dissociate upon extensive dialysis or passage through Sephadex G-25. The compound behaves as a pyridoxamine phosphate derivative and not as a coenzyme-substrate complex, since both competing anions and dicarboxylic acid inhibitors still bind to the phosphopyridoxyl trifluoroethylamine enzyme. The 19F NMR spectra of the enzyme-bound phosphopyridoxyl trifluoroethylamine were measured as a function of pH, ionic strength, and temperature. The 19F MNR of the enzyme-bound coenzyme derivative revealed no predetermined asymmetry in the subunits of aspartate transaminase insolution in terms of differences in chemical shift or resonance line shape between the two environments. A pH-dependent chemical shift change of the single 19F resonance was observed, which is consistent with the influence of a single ionization with an apparent pKa of 8.4 in 0.10 M KCl at 30 degrees. Increasing the ionic strength resulted in increasing values for the observed pKa, the highest recorded value was 9.1 in 3.0 M KCl. The temperature dependence of the pH titration of the chemical shift gives deltaH' of ionization of 10.5 kcal/mol. The evidence suggests a possible epsilon-amino group, electrostatically affected by positive charges, being responsible for the titration effect of the active site-bound fluorine derivative of pyridoxamine phosphate.", "contents": "Fluorine-19 as a covalent active site-directed magnetic resonance probe in aspartate transaminase. Phosphypyridoxyl trifluoroethylamine has been synthesized as an active site-directed 19F NMR probe for aspartate transaminase. This coenzyme derivative adds stoichiometrically to the apotransaminase as observed by both fluorescence and circular dichroism measurements. The fluorinated phosphypyridoxamine derivative, when bound to the apotransaminase, will not dissociate upon extensive dialysis or passage through Sephadex G-25. The compound behaves as a pyridoxamine phosphate derivative and not as a coenzyme-substrate complex, since both competing anions and dicarboxylic acid inhibitors still bind to the phosphopyridoxyl trifluoroethylamine enzyme. The 19F NMR spectra of the enzyme-bound phosphopyridoxyl trifluoroethylamine were measured as a function of pH, ionic strength, and temperature. The 19F MNR of the enzyme-bound coenzyme derivative revealed no predetermined asymmetry in the subunits of aspartate transaminase insolution in terms of differences in chemical shift or resonance line shape between the two environments. A pH-dependent chemical shift change of the single 19F resonance was observed, which is consistent with the influence of a single ionization with an apparent pKa of 8.4 in 0.10 M KCl at 30 degrees. Increasing the ionic strength resulted in increasing values for the observed pKa, the highest recorded value was 9.1 in 3.0 M KCl. The temperature dependence of the pH titration of the chemical shift gives deltaH' of ionization of 10.5 kcal/mol. The evidence suggests a possible epsilon-amino group, electrostatically affected by positive charges, being responsible for the titration effect of the active site-bound fluorine derivative of pyridoxamine phosphate."}
{"id": "PMID:5433", "title": "Spot hemoglobin. Studies on the Root effect hemoglobin of a marine teleost.", "content": "The Spot, Leiostomus xanthrus, has a single tetrameric hemoglobin. Structural studies indicate the presence of alpha- and beta-like chains with COOH-terminal sequences of --Arg and --TYR-His, respectively, the same as is found in human hemoglobin. Spot hemoglobin possesses a Root effect: a heterotropic control mechanism like the Bohr effect but with more extreme pH dependence in the equilibria and kinetics of O2 and CO binding. The Root effect seems to be a molecular adaptation, in that pH- and anion-sensitive hemoglobins may help fish achieve neutral buoyancy by facilitating O2 delivery to the swim bladder. Changes in the kinetics of both \"on\" and \"off\" processes contribute to the greatly decreased ligand affinity of Spot hemoglobin at low pH. The time course ofligand combination at low pH is biphasic and wavelength dependent, suggesting a differential effect of pH on the alpha- and beta-like chains. The change in the shape of the ligand-binding curve with pH may be interpreted in terms of a proton-dependent transition between low (T) and high (R) affinity conformations. However, this may not be the only mechanism, since differential pH effects on the two types of chains may also contribute to the observed pH dependence.", "contents": "Spot hemoglobin. Studies on the Root effect hemoglobin of a marine teleost. The Spot, Leiostomus xanthrus, has a single tetrameric hemoglobin. Structural studies indicate the presence of alpha- and beta-like chains with COOH-terminal sequences of --Arg and --TYR-His, respectively, the same as is found in human hemoglobin. Spot hemoglobin possesses a Root effect: a heterotropic control mechanism like the Bohr effect but with more extreme pH dependence in the equilibria and kinetics of O2 and CO binding. The Root effect seems to be a molecular adaptation, in that pH- and anion-sensitive hemoglobins may help fish achieve neutral buoyancy by facilitating O2 delivery to the swim bladder. Changes in the kinetics of both \"on\" and \"off\" processes contribute to the greatly decreased ligand affinity of Spot hemoglobin at low pH. The time course ofligand combination at low pH is biphasic and wavelength dependent, suggesting a differential effect of pH on the alpha- and beta-like chains. The change in the shape of the ligand-binding curve with pH may be interpreted in terms of a proton-dependent transition between low (T) and high (R) affinity conformations. However, this may not be the only mechanism, since differential pH effects on the two types of chains may also contribute to the observed pH dependence."}
{"id": "PMID:5434", "title": "Site-site interactions among insulin receptors. Characterization of the negative cooperativity.", "content": "By studying the dissociation of 125I-instulin from its receptors in the absence and phe negatively cooperative type for the insulin receptors. In the present study we extend oy purified mouse and rat liver membranes as well as in human circulating monocytes and human cultured lymphocytes demonstrated negative cooperativity that was extraordinarily simn membranes more slowly than it does from its receptors on whole cells. The dissociaty a small percentage of the receptor sites (1 to 5%), are sufficient to accelerate dissociation of hormone from receptor. At these insulin concentrations insulin is entirely monomeric, and in fact at higher concentrations of insulin (greater than 10(-7) M) where insulin dimers predominate, the cooperativity effect is progressively lost. The dissociation rate of 125I-insulin alone (that is at very low fractional saturation of receptors) was markedly accelerated by dripping the pH from 8.0 to 5.0, whereas the dissociation of 125I-insulin at high receptor occupancy was only slightly accelerated by the fall in pH. The dissociation rate was directly related to temperature, but the dissociation rate of 125I-insulin at low receptor occupancy was much more affected by reduction in temperature and showed a sharp transition at 21 degrees. Urea at concentrations as low as 1 M produced a marked acceleration of 125I-insulin dissociation. Divalent cations (calcium and magnesium) appear to stabilize the insulin-receptor interaction, since higher degrees of receptor occupancy were required to achieve a given rate of dissociation of 125I-insulin. These data make it likely that the insulin receptors exist as oligomeric structures or clusters in the plasma membrane. Insulin receptor sites appear to switch from a \"slow dissociating\" state to a \"fast dissociating\" state when their occupancy increases; the proportion of sites in each state is a function of occupancy of the receptor sites by the insulin monomer as well as of the physiochemical environment. Other models which could explain apparent negative cooperativity besides site-site interactions, i.e. polymerization of the hormone, steric or electrostatic hindrance due to ligand-ligand interactions, or unstirred (Noyes-Whitney) layers are considered unlikely in the case of insulin receptors on both experimental and theoretical grounds.", "contents": "Site-site interactions among insulin receptors. Characterization of the negative cooperativity. By studying the dissociation of 125I-instulin from its receptors in the absence and phe negatively cooperative type for the insulin receptors. In the present study we extend oy purified mouse and rat liver membranes as well as in human circulating monocytes and human cultured lymphocytes demonstrated negative cooperativity that was extraordinarily simn membranes more slowly than it does from its receptors on whole cells. The dissociaty a small percentage of the receptor sites (1 to 5%), are sufficient to accelerate dissociation of hormone from receptor. At these insulin concentrations insulin is entirely monomeric, and in fact at higher concentrations of insulin (greater than 10(-7) M) where insulin dimers predominate, the cooperativity effect is progressively lost. The dissociation rate of 125I-insulin alone (that is at very low fractional saturation of receptors) was markedly accelerated by dripping the pH from 8.0 to 5.0, whereas the dissociation of 125I-insulin at high receptor occupancy was only slightly accelerated by the fall in pH. The dissociation rate was directly related to temperature, but the dissociation rate of 125I-insulin at low receptor occupancy was much more affected by reduction in temperature and showed a sharp transition at 21 degrees. Urea at concentrations as low as 1 M produced a marked acceleration of 125I-insulin dissociation. Divalent cations (calcium and magnesium) appear to stabilize the insulin-receptor interaction, since higher degrees of receptor occupancy were required to achieve a given rate of dissociation of 125I-insulin. These data make it likely that the insulin receptors exist as oligomeric structures or clusters in the plasma membrane. Insulin receptor sites appear to switch from a \"slow dissociating\" state to a \"fast dissociating\" state when their occupancy increases; the proportion of sites in each state is a function of occupancy of the receptor sites by the insulin monomer as well as of the physiochemical environment. Other models which could explain apparent negative cooperativity besides site-site interactions, i.e. polymerization of the hormone, steric or electrostatic hindrance due to ligand-ligand interactions, or unstirred (Noyes-Whitney) layers are considered unlikely in the case of insulin receptors on both experimental and theoretical grounds."}
{"id": "PMID:5435", "title": "Rabbit skeletal muscle glycogen synthase. II. Enzyme phosphorylation state and effector concentrations as interacting control parameters.", "content": "The effects of several inhibitors (ATP, ADP, AMP, UDP, and P1) and activators (Mg2+, glucose-6-P) of rabbit muscle glycogen synthase (UDP-glucose:glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11) were studied in relation to the phosphorylation state of the purified enzyme. All the modifiers had increasing effects with enzyme of increasing alkali-labile phosphate content. In experiments where combinations of effectors were present, it was apparent that (a) concentrations of modifiers in the physiological range could be significant in determining enzymic activity and (b) the sensitivity of the reaction rate to changes in phosphorylation state was critically dependent on the concentration of the small molecules. Changes in the phosphorylation of the enzyme corresponding to changes in the %I activity reported in the literature for studies in vivo were capable of producing large alterations in glycogen synthase activity. Because the magnitudes of such changes were dependent on the effector concentrations, there may be an integration of local cellular control, through small molecule effects, with hormonal control, through the phosphorylation state of glycogen synthase.", "contents": "Rabbit skeletal muscle glycogen synthase. II. Enzyme phosphorylation state and effector concentrations as interacting control parameters. The effects of several inhibitors (ATP, ADP, AMP, UDP, and P1) and activators (Mg2+, glucose-6-P) of rabbit muscle glycogen synthase (UDP-glucose:glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11) were studied in relation to the phosphorylation state of the purified enzyme. All the modifiers had increasing effects with enzyme of increasing alkali-labile phosphate content. In experiments where combinations of effectors were present, it was apparent that (a) concentrations of modifiers in the physiological range could be significant in determining enzymic activity and (b) the sensitivity of the reaction rate to changes in phosphorylation state was critically dependent on the concentration of the small molecules. Changes in the phosphorylation of the enzyme corresponding to changes in the %I activity reported in the literature for studies in vivo were capable of producing large alterations in glycogen synthase activity. Because the magnitudes of such changes were dependent on the effector concentrations, there may be an integration of local cellular control, through small molecule effects, with hormonal control, through the phosphorylation state of glycogen synthase."}
{"id": "PMID:5436", "title": "Kinetic study of the action of snake venom phospholipase A2 on human serum high density lipoprotein 3.", "content": "The hydrolysis of the phospholipids of intact human serum high density lipoprotein 3 (HDL3) by pure alpha-phospholipase A2 from Crotalus adamanteus was studied by pH-stat titration. The enzyme quantitatively hydrolyzed phosphatidylcholine and phosphatidylethanolamine and left sphinogomyelin intact, yielding a stable and water-soluble modified HDL. Lysophospholipids and free fatty acids, the products of hydrolysis, remained in the lipoprotein. When 1 mol of defatted bovine serum albumin/mol of substrate phospholipids was added to the reaction mixture, up to 60% of the fatty acids and 85% of the lysophospholipids were removed from the modified lipoprotein. The immunological reactivity of the hydrolyzed HDL remained unaltered in both the presence and absence of albumin. The changes in the physical properties of the lipoprotein during hydrolysis were rather small, the most notable being an increase in the hydrated density and in the electrophoretic mobility in alkaline buffers. The hydrolysis followed an apparent first order time course with product inhibition (KI) and yielded values of kcat/Km = 7 X 10(5 M(-1)s(-1) and KI congruent to 1 X 10(-4) M. Addition of albumin to the reaction mixture relieved the product inhibition without any alteration of the kinetic parameters. High concentrations of albumin protected some of the substrate phospholipids from hydrolysis, presumably through complexation to the lipoprotein. The Arrhenius plot for the experimental first order rate constant in the absence of albumin (kexp = kcat (KI/Km)) was linear between 15 degrees and 47 degrees, indicating the absence of any phospholipid phase transitions and yielding an activation energy of 15.2 kcal/mol. From the accessibility of the HDL phospholipids to phospholipase A2 one concludes that the phosphatidylcholine and phosphatidylethanolamine are located at, or are in rapid equilibrium with, the surface of this lipoprotein. It also appears that these phospholipids are not essential for maintaining the supramolecular properties of the lipoprotein in vitro. Thsu the study of the modified Hdl should provide valuable information concenring the structure and function of this lipoprotein particularly with regard to the role played by shiingomyelin.", "contents": "Kinetic study of the action of snake venom phospholipase A2 on human serum high density lipoprotein 3. The hydrolysis of the phospholipids of intact human serum high density lipoprotein 3 (HDL3) by pure alpha-phospholipase A2 from Crotalus adamanteus was studied by pH-stat titration. The enzyme quantitatively hydrolyzed phosphatidylcholine and phosphatidylethanolamine and left sphinogomyelin intact, yielding a stable and water-soluble modified HDL. Lysophospholipids and free fatty acids, the products of hydrolysis, remained in the lipoprotein. When 1 mol of defatted bovine serum albumin/mol of substrate phospholipids was added to the reaction mixture, up to 60% of the fatty acids and 85% of the lysophospholipids were removed from the modified lipoprotein. The immunological reactivity of the hydrolyzed HDL remained unaltered in both the presence and absence of albumin. The changes in the physical properties of the lipoprotein during hydrolysis were rather small, the most notable being an increase in the hydrated density and in the electrophoretic mobility in alkaline buffers. The hydrolysis followed an apparent first order time course with product inhibition (KI) and yielded values of kcat/Km = 7 X 10(5 M(-1)s(-1) and KI congruent to 1 X 10(-4) M. Addition of albumin to the reaction mixture relieved the product inhibition without any alteration of the kinetic parameters. High concentrations of albumin protected some of the substrate phospholipids from hydrolysis, presumably through complexation to the lipoprotein. The Arrhenius plot for the experimental first order rate constant in the absence of albumin (kexp = kcat (KI/Km)) was linear between 15 degrees and 47 degrees, indicating the absence of any phospholipid phase transitions and yielding an activation energy of 15.2 kcal/mol. From the accessibility of the HDL phospholipids to phospholipase A2 one concludes that the phosphatidylcholine and phosphatidylethanolamine are located at, or are in rapid equilibrium with, the surface of this lipoprotein. It also appears that these phospholipids are not essential for maintaining the supramolecular properties of the lipoprotein in vitro. Thsu the study of the modified Hdl should provide valuable information concenring the structure and function of this lipoprotein particularly with regard to the role played by shiingomyelin."}
{"id": "PMID:5437", "title": "Regulation of steady state level of phosphoenzyme and ATP synthesis in sarcoplasmic reticulum vesicles during reversal of the Ca2+ pump.", "content": "The role of the Ca2+ concentration gradient in ATP synthesis and membrane phosphorylation by Pi was investigated in sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle. The Pi concentration required to attain 50% of the maximal membrane phosphorylation varies significantly in the pH range of 5.5 to 4.5, the optimal being at pH 6.0. In the pH range of 6.0 to 7.0, this concentration of Pi was 4- to 10-fold higher in empty vesicles than in vesicles loaded with calcium phosphate, i.e. having transmembrane Ca2+ concentration gradient. ATP, ADP, and Ca2+ inhibit the membrane phosphorylation by Pi, the inhibition being greater at pH 7.0 than at pH 6.0. The pH profile for ATP synthesis shows a higher optimum than for membrane phosphorylation. The optimum pH for synthesis, but not for phosphorylation depends on whether the vesicles were previously loaded with calcium phosphate or with calcium oxalate. Addition of Ca2+ to the assay medium inhibits the extent of membrane phosphorylation and the rate of ATP synthesis to different extents. Evidence is presented that the rate of membrane phosphorylation by Pi is higher than the rate by which the phosphoprotein transfers its pohsphate to ADP for the ATP synthesis.", "contents": "Regulation of steady state level of phosphoenzyme and ATP synthesis in sarcoplasmic reticulum vesicles during reversal of the Ca2+ pump. The role of the Ca2+ concentration gradient in ATP synthesis and membrane phosphorylation by Pi was investigated in sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle. The Pi concentration required to attain 50% of the maximal membrane phosphorylation varies significantly in the pH range of 5.5 to 4.5, the optimal being at pH 6.0. In the pH range of 6.0 to 7.0, this concentration of Pi was 4- to 10-fold higher in empty vesicles than in vesicles loaded with calcium phosphate, i.e. having transmembrane Ca2+ concentration gradient. ATP, ADP, and Ca2+ inhibit the membrane phosphorylation by Pi, the inhibition being greater at pH 7.0 than at pH 6.0. The pH profile for ATP synthesis shows a higher optimum than for membrane phosphorylation. The optimum pH for synthesis, but not for phosphorylation depends on whether the vesicles were previously loaded with calcium phosphate or with calcium oxalate. Addition of Ca2+ to the assay medium inhibits the extent of membrane phosphorylation and the rate of ATP synthesis to different extents. Evidence is presented that the rate of membrane phosphorylation by Pi is higher than the rate by which the phosphoprotein transfers its pohsphate to ADP for the ATP synthesis."}
{"id": "PMID:5438", "title": "Acetyl coenzyme A carbosylase. Circular dichroism studies of Escherichia coli biotin carboxyl carrier protein.", "content": "The biotin carboxyl carrier protein (BCCP) component of Escherichia coli acetyl coenzyme A carboxylase and three peptides derived from BCCP by proteolytic digestion have been examined by circular dichroism spectroscopy. BCCP, which has a peptide molecular weight of 22,500, has a spectrum typical of globular proteins with negative extrema at 222 nm and 208 nm. The two smallest peptides, BCCP(SC) and BCCP(9,100), with molecular weights of 8,900 and 9,100, respectively, exhibit unusual positive CD bands centered at 237 nm and 220 nm. BCCP(10,400), with a molecular weight of 10,400, has a CD spectrum intermediate between BCCP and that of the smallest peptides. Since d-biotin exhibits a positive CD band at 233 nm, it was suspected that the biotin prosthetic group might be the chromophore responsible for the 237 nm CD band seen in BCCP(SC) and BCCP(9,100). Enzymatic carboxylation of BCCP(SC) to form CO2-BCCP(SC) caused the CD spectrum to change with a shift of the 237 nm band to 232 nm. The positive CD band at 220 nm was unaffected by carboxylation of the biotin prosthetic group. These date suggest that the 237 nm signal may be due either to the biotin which acts as a chromophore directly or to a chromophore that is perturbed by the carboxylation of biotin. A spectropolarimetric titration was carried out to investigate the possible contribution of the single tyrosine residue of BCCP(SC) to the CD spectrum of this peptide. At pH values over 9 the CD spetrum changed with the disappearance of the 237 nm band, suggesting that tyrosine might contribute to this CD band. Denaturation of BCCP(SC) or BCCP(9,100) with 8 M urea of 6 M guanidine HCl abolished the positive CD bands and resulted in spectra typical of a random coil, whereas treatment of BCCP(SC) with 1% sodium dodecyl sulfate abolished the positive bands and left a spectrum exhibiting a shoulder at 222 nm and a negative band at 205 nm, suggestive of a high degree of ordered structure. It is concluded that the CD band at 237 nm in BCCP(SC) and BCCP(9,100) is prabably due to a noncovalent interaction of biotin with an amino acid residue(s) of the protein. It is suggested that the biotin prosthetic group is partially buried in the surface of the protein, rather than swinging free at the end of the lysine side chain through which it is covalently linked to the protein, to permit this interaction to occur.", "contents": "Acetyl coenzyme A carbosylase. Circular dichroism studies of Escherichia coli biotin carboxyl carrier protein. The biotin carboxyl carrier protein (BCCP) component of Escherichia coli acetyl coenzyme A carboxylase and three peptides derived from BCCP by proteolytic digestion have been examined by circular dichroism spectroscopy. BCCP, which has a peptide molecular weight of 22,500, has a spectrum typical of globular proteins with negative extrema at 222 nm and 208 nm. The two smallest peptides, BCCP(SC) and BCCP(9,100), with molecular weights of 8,900 and 9,100, respectively, exhibit unusual positive CD bands centered at 237 nm and 220 nm. BCCP(10,400), with a molecular weight of 10,400, has a CD spectrum intermediate between BCCP and that of the smallest peptides. Since d-biotin exhibits a positive CD band at 233 nm, it was suspected that the biotin prosthetic group might be the chromophore responsible for the 237 nm CD band seen in BCCP(SC) and BCCP(9,100). Enzymatic carboxylation of BCCP(SC) to form CO2-BCCP(SC) caused the CD spectrum to change with a shift of the 237 nm band to 232 nm. The positive CD band at 220 nm was unaffected by carboxylation of the biotin prosthetic group. These date suggest that the 237 nm signal may be due either to the biotin which acts as a chromophore directly or to a chromophore that is perturbed by the carboxylation of biotin. A spectropolarimetric titration was carried out to investigate the possible contribution of the single tyrosine residue of BCCP(SC) to the CD spectrum of this peptide. At pH values over 9 the CD spetrum changed with the disappearance of the 237 nm band, suggesting that tyrosine might contribute to this CD band. Denaturation of BCCP(SC) or BCCP(9,100) with 8 M urea of 6 M guanidine HCl abolished the positive CD bands and resulted in spectra typical of a random coil, whereas treatment of BCCP(SC) with 1% sodium dodecyl sulfate abolished the positive bands and left a spectrum exhibiting a shoulder at 222 nm and a negative band at 205 nm, suggestive of a high degree of ordered structure. It is concluded that the CD band at 237 nm in BCCP(SC) and BCCP(9,100) is prabably due to a noncovalent interaction of biotin with an amino acid residue(s) of the protein. It is suggested that the biotin prosthetic group is partially buried in the surface of the protein, rather than swinging free at the end of the lysine side chain through which it is covalently linked to the protein, to permit this interaction to occur."}
{"id": "PMID:5439", "title": "Pulse radiolytic investigation of single heme group reduction in hum an methemoglobin.", "content": "Reduction of one of the four heme groups of human aquomethemoglobin A has been investigated by the pulse radiolysis method. The reactivity of e-a-q, the hydrated electron, with methemoglobin was determined by observing this species directly. The separate reactions of the hydroxy yl radical and hydrogen atom, as well as of e-a-q, were studied by observing absorbance changes in the protein spectrum over the wavelength range 290 to 600nm, with appropriate scavengers in solution...", "contents": "Pulse radiolytic investigation of single heme group reduction in hum an methemoglobin. Reduction of one of the four heme groups of human aquomethemoglobin A has been investigated by the pulse radiolysis method. The reactivity of e-a-q, the hydrated electron, with methemoglobin was determined by observing this species directly. The separate reactions of the hydroxy yl radical and hydrogen atom, as well as of e-a-q, were studied by observing absorbance changes in the protein spectrum over the wavelength range 290 to 600nm, with appropriate scavengers in solution..."}
{"id": "PMID:5440", "title": "Enzymatic attack on side chains of synthetic polymers. Chymotrypsin-catalyzed hydrolysis of specific substrate groups attached to acrylamide or acrylic acid co-polymers.", "content": "Three vinyl monomers, M-1, M-3, and M-5, in which L-phenylalanine p-nitroanilide was acylated with CH2==CHCONH(CH2)nCO--(n = 1, 3, 5) were synthesized. They were co-polymerized with a large excess of acrylamide (co-polymers PAm-1, PAm-3, and PAm-5) and with a large excess of acrylic acid (co-polymers PAc=1, PAc-3, and PCc-5). In addition, M-5 was co-polymerized with acrylamide containing 2.8 mol % of the hydrophobic monomer N-acrylyl-1-naphthylamine (co-polymer PAm-5N). The rates of the chymotrypsin-catalyzed hydrolysis of the nitroanilide groups of M-5 and the various co-polymers were determined over a range of pH. For some of the systems data were also obtained over a range of substrate concentrations to derive values for Vmax and Km. Results obtained with PAm-5 were found to be independent of the chain length of the co-polymer. At pH 7, 25 degrees and with 2.7 X 10(-6) M enzyme, Vmax values for M-5, PAm-k, PAm-5N, and PAc-5 were 5.5, 5.5, 10, and 3.6 X 10(-8) M/S, while Km values were 8.5, 16.5, 10, and 2.2 X 10(-5),respectively, With PAc-5, the pH activity profile was shifted to higher acidities as compared to the profiles obtained with M-5 and PAm-5. The susceptibility of the co-polymers to chymotrypsin attack decreases sharply with a decreasing spacing of the L-phenylalanine p-nitroanilide residue from the backbone of the polymer chains.", "contents": "Enzymatic attack on side chains of synthetic polymers. Chymotrypsin-catalyzed hydrolysis of specific substrate groups attached to acrylamide or acrylic acid co-polymers. Three vinyl monomers, M-1, M-3, and M-5, in which L-phenylalanine p-nitroanilide was acylated with CH2==CHCONH(CH2)nCO--(n = 1, 3, 5) were synthesized. They were co-polymerized with a large excess of acrylamide (co-polymers PAm-1, PAm-3, and PAm-5) and with a large excess of acrylic acid (co-polymers PAc=1, PAc-3, and PCc-5). In addition, M-5 was co-polymerized with acrylamide containing 2.8 mol % of the hydrophobic monomer N-acrylyl-1-naphthylamine (co-polymer PAm-5N). The rates of the chymotrypsin-catalyzed hydrolysis of the nitroanilide groups of M-5 and the various co-polymers were determined over a range of pH. For some of the systems data were also obtained over a range of substrate concentrations to derive values for Vmax and Km. Results obtained with PAm-5 were found to be independent of the chain length of the co-polymer. At pH 7, 25 degrees and with 2.7 X 10(-6) M enzyme, Vmax values for M-5, PAm-k, PAm-5N, and PAc-5 were 5.5, 5.5, 10, and 3.6 X 10(-8) M/S, while Km values were 8.5, 16.5, 10, and 2.2 X 10(-5),respectively, With PAc-5, the pH activity profile was shifted to higher acidities as compared to the profiles obtained with M-5 and PAm-5. The susceptibility of the co-polymers to chymotrypsin attack decreases sharply with a decreasing spacing of the L-phenylalanine p-nitroanilide residue from the backbone of the polymer chains."}
{"id": "PMID:5441", "title": "Purification and properties of a highly potent antitumor glutaminase-asparaginase from Pseudomonas 7Z.", "content": "Crystalline glutaminase-asparaginase which is effective against solid as well as ascites tumors was prepared from soil isolate organism Pseudomonas 7A. This enzyme has a ration of Vmax for L-glutamine and L-asparagine of 2.0. The presence of glutamic acid in the growth medium is essential for optimal enzyme production and glucose inhibits the production of glutaminase-asparaginase. The purification procedure provides an overall yield of 40 to 45% from crude cell extract to homogeneous glutaminase-asparaginase and is adaptable to large scale production of the enzyme. The specific activity of homogeneous enzyme is 160 +/- 15 i.u./mg of protein and the E1% 280 is 9.8. No disulfide or sulfhydryl groups appear to be present on the enzyme. The isoelectric point of glutaminase-asparaginase by isoelectric focusing on ampholine polyacrylamide gel plates is 5.8. The Km values for L-glutamine and L-asparagine are 4.6 and 4.4 X 10(-6) M, respectively. The enzyme catalyzes the hydrolysis of the D isomers of glutamine and asparagine at 87 and 69% the rate of the respective L isomers. L-Glutamic acid gamma-monohydroxamate is hydrolyzed at approximately the same rate as L-glutamine. The enzyme is not inhibited by ethylenediaminetetraacetate (0.1 mM), L-glutamate (30 mM), or L-aspartate (30 mM). Ammonium sulfate (10 mM) inhibits the enzymatic activity. The plasma half-life of Pseudomonas 7A glutaminase-asparaginase if 13 hours in normal mice and 43 hours in mice infected with the lactate dehydrogenase-elevating virus.", "contents": "Purification and properties of a highly potent antitumor glutaminase-asparaginase from Pseudomonas 7Z. Crystalline glutaminase-asparaginase which is effective against solid as well as ascites tumors was prepared from soil isolate organism Pseudomonas 7A. This enzyme has a ration of Vmax for L-glutamine and L-asparagine of 2.0. The presence of glutamic acid in the growth medium is essential for optimal enzyme production and glucose inhibits the production of glutaminase-asparaginase. The purification procedure provides an overall yield of 40 to 45% from crude cell extract to homogeneous glutaminase-asparaginase and is adaptable to large scale production of the enzyme. The specific activity of homogeneous enzyme is 160 +/- 15 i.u./mg of protein and the E1% 280 is 9.8. No disulfide or sulfhydryl groups appear to be present on the enzyme. The isoelectric point of glutaminase-asparaginase by isoelectric focusing on ampholine polyacrylamide gel plates is 5.8. The Km values for L-glutamine and L-asparagine are 4.6 and 4.4 X 10(-6) M, respectively. The enzyme catalyzes the hydrolysis of the D isomers of glutamine and asparagine at 87 and 69% the rate of the respective L isomers. L-Glutamic acid gamma-monohydroxamate is hydrolyzed at approximately the same rate as L-glutamine. The enzyme is not inhibited by ethylenediaminetetraacetate (0.1 mM), L-glutamate (30 mM), or L-aspartate (30 mM). Ammonium sulfate (10 mM) inhibits the enzymatic activity. The plasma half-life of Pseudomonas 7A glutaminase-asparaginase if 13 hours in normal mice and 43 hours in mice infected with the lactate dehydrogenase-elevating virus."}
{"id": "PMID:5442", "title": "Regulation of secretion from the adrenal medulla. Evidence for adenylate cyclase activity in secretory vesicle membranes.", "content": "Adenylate cyclase activity has been found in purified secretory vesicle membranes from the adrenal medulla. Activity was detected both by formation of radioactive cAMP from [alpha-32P]ATP and by the competitive protein binding assay for cAMP. Activity was highest at pH 8.0 to 8.5, and was stimulated by sodium fluoride and GppNHp, a GTP analogue known to stimulate adenylate cyclase activity in plasma membrane preparations. The reaction rate was strongly dependent on the molar ratio of Mg2+:ATP in the system. This is the first demonstration of adenylate cyclase in a secretory vesicle membrane.", "contents": "Regulation of secretion from the adrenal medulla. Evidence for adenylate cyclase activity in secretory vesicle membranes. Adenylate cyclase activity has been found in purified secretory vesicle membranes from the adrenal medulla. Activity was detected both by formation of radioactive cAMP from [alpha-32P]ATP and by the competitive protein binding assay for cAMP. Activity was highest at pH 8.0 to 8.5, and was stimulated by sodium fluoride and GppNHp, a GTP analogue known to stimulate adenylate cyclase activity in plasma membrane preparations. The reaction rate was strongly dependent on the molar ratio of Mg2+:ATP in the system. This is the first demonstration of adenylate cyclase in a secretory vesicle membrane."}
{"id": "PMID:5443", "title": "In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate.", "content": "Superoxide dismutase was assayed by a method which takes advantage of the inhibitory action of superoxide dismutase (or tissues which contain superoxide dismutase) on the rate of autooxidation of 6-hydroxydopamine. Incubation of pure superoxide dismutase of homogenates of brain or liver with 10(-3) M diethyldithiocarbamate for 1.5 hours resulted in total loss of superoxide dismutase activity. Inhibition of superoxide dismutase was not reversed by dialysis, but after dialysis, enzymatic activity was restored with CuSO4. When 1.5 g of diethyldithiocarbamate/kg were injected into mice, the superoxide dismutase activity at 3 hours was decreased by 86%, 71%, and 48%, respectively, in whole blood, liver, and brain. A dose of 0.5 g of diethyldithiocarbamate/kg lowered the superoxide dismutase activity by 42% in liver at 3 hours. A study of the time course for inhibiton of superoxide dismutase in liver after 1.5 g of diethyldithiocarbamate/kg, showed a maximum decrease (81%) within 1 hour, with a slow return to 64% of normal by 24 hours. Inhibition of superoxide dismutase in vivo and in vitro was confirmed with other assay systems based on the autooxidation of pyrogallol or epinephrine or on reduction of cytochrome c or intro blue tetrazolium. Treatment of animals with diethyldithiocarbamate may provide a useful experimental model to study the role of superoxide dismutase in various tissues.", "contents": "In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate. Superoxide dismutase was assayed by a method which takes advantage of the inhibitory action of superoxide dismutase (or tissues which contain superoxide dismutase) on the rate of autooxidation of 6-hydroxydopamine. Incubation of pure superoxide dismutase of homogenates of brain or liver with 10(-3) M diethyldithiocarbamate for 1.5 hours resulted in total loss of superoxide dismutase activity. Inhibition of superoxide dismutase was not reversed by dialysis, but after dialysis, enzymatic activity was restored with CuSO4. When 1.5 g of diethyldithiocarbamate/kg were injected into mice, the superoxide dismutase activity at 3 hours was decreased by 86%, 71%, and 48%, respectively, in whole blood, liver, and brain. A dose of 0.5 g of diethyldithiocarbamate/kg lowered the superoxide dismutase activity by 42% in liver at 3 hours. A study of the time course for inhibiton of superoxide dismutase in liver after 1.5 g of diethyldithiocarbamate/kg, showed a maximum decrease (81%) within 1 hour, with a slow return to 64% of normal by 24 hours. Inhibition of superoxide dismutase in vivo and in vitro was confirmed with other assay systems based on the autooxidation of pyrogallol or epinephrine or on reduction of cytochrome c or intro blue tetrazolium. Treatment of animals with diethyldithiocarbamate may provide a useful experimental model to study the role of superoxide dismutase in various tissues."}
{"id": "PMID:5444", "title": "Internal pH of isolated chromaffin vesicles.", "content": "The passive permeability of isolated chromaffin vesicles to H+ and the internal pH of the vesicles under various conditions were measured. Potentiometric measurements of K+ and H+ fluxes in the presence of selected ionophores and uncouplers indicated that the membrane is highly impermeable to both protons and potassium. deltapH across the chromaffin granule membrane was measured by [14C]methylamine distribution. At pH 6.85, The deltapH WAS 1.16 WITH THE INTRAVESICULAR SPACE BEING FOUND ACIDIC. Varying the external pH produced an equivalent change in the deltapH, WITH EXTRAPOLATION TO ZERO DEltapH yielding a value of pH  5.5, WHICH IS TAKEN AS AN INDICATION OF THE PH of the intravesicular space. The pH gradient could be enhanced or collapsed by the addition of ionophores and uncouplers under varying ionic conditions. deltapH was constant for granules suspended in various ionic media, suggesting that the deltapH did not arise secondarily due to the establishment of a Donnan equilibrium. The significance of the proton impermeability and deltapH is discussed in terms of regulation of the uptake and storage of catecholamines in bovine chromaffin granules.", "contents": "Internal pH of isolated chromaffin vesicles. The passive permeability of isolated chromaffin vesicles to H+ and the internal pH of the vesicles under various conditions were measured. Potentiometric measurements of K+ and H+ fluxes in the presence of selected ionophores and uncouplers indicated that the membrane is highly impermeable to both protons and potassium. deltapH across the chromaffin granule membrane was measured by [14C]methylamine distribution. At pH 6.85, The deltapH WAS 1.16 WITH THE INTRAVESICULAR SPACE BEING FOUND ACIDIC. Varying the external pH produced an equivalent change in the deltapH, WITH EXTRAPOLATION TO ZERO DEltapH yielding a value of pH  5.5, WHICH IS TAKEN AS AN INDICATION OF THE PH of the intravesicular space. The pH gradient could be enhanced or collapsed by the addition of ionophores and uncouplers under varying ionic conditions. deltapH was constant for granules suspended in various ionic media, suggesting that the deltapH did not arise secondarily due to the establishment of a Donnan equilibrium. The significance of the proton impermeability and deltapH is discussed in terms of regulation of the uptake and storage of catecholamines in bovine chromaffin granules."}
{"id": "PMID:5445", "title": "Triglyceride, diglyceride, monoglyceride, and cholesterol ester hydrolases in chicken adipose tissue activated by adenosine 3':5'-Monophosphate-dependent protein kinase. Chromatographic resolution and immunochemical differentiation from lipoprotein lipase.", "content": "Hormone-sensitive lipase and cholesterol ester hydrolase of chicken adipose tissue were markedly activated by adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (on the average, 235 to 275%; occasionally as much as 1000%). Diglyceride and monoglyceride hydrolases were also activated, but to a lesser extent (60 to 87%). The activation of all four hydrolases was inhibited by protein kinase inhibitor and reversed by the addition of exogenous protein kinase. Following activation by cAMP-dependent protein kinase, all four hydrolases were deactivated in a Mg2+-dependent reaction and then reactivated to or near initial levels on incubation with cAMP and Mg2+-ATP. The reversible deactivation is assumed to reflect activity of one or more protein phosphatases. The maximum activation obtainable for the four hydrolases decreased when the tissue had been previously exposed to glucagon, indicating that the glucagon-induced activation was probably similar to or identical with the activation demonstrated in cell-free preparations. The pH optima for the four hydrolase activities were similar (7.13 to 7.38). Although the absolute activities and relative degrees of kinase activation differed according to the particular emulsified substrates used, the results do not rule out the possibility that all four hydrolase activities are referable to a single hormone-sensitive hydrolase. Hormone-sensitive acyl hydrolases were separated from lipoprotein lipase by heparin-Sepharose affinity chromatography. Lipoprotein lipase was active against triolein, diolein, and monoolein, but not cholesterol oleate. Incubation of lipoprotein lipase with exogenous protein kinase, cAMP, and Mg2+ATP had no effect on any of the three hydrolase activities. Lipoprotein lipase was further purified to homogeneity and used to prepare antiserum in rabbits. The immunoglobin G fraction from these antisera completely inhibited lipoprotein lipase eluted from heparin-Sepharose columns. However, the hormone-sensitive hydrolase activities (not retained on heparin-Sepharose affinity chromatography) were not inhibited by anti-lipoprotein lipase immunoglobin G, and anti-lopoprotein lipase immunoglobin G did not affect the activation process in crude fractions. Thus, hormone-sensitive lipase and lipoprotein lipase, functionally distinct enzymes, have been physically resolved and immunochemically distinguished. Apparently lipoprotein lipase activity is not regulated, at least directly, by cAMP-dependent protein kinase.", "contents": "Triglyceride, diglyceride, monoglyceride, and cholesterol ester hydrolases in chicken adipose tissue activated by adenosine 3':5'-Monophosphate-dependent protein kinase. Chromatographic resolution and immunochemical differentiation from lipoprotein lipase. Hormone-sensitive lipase and cholesterol ester hydrolase of chicken adipose tissue were markedly activated by adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (on the average, 235 to 275%; occasionally as much as 1000%). Diglyceride and monoglyceride hydrolases were also activated, but to a lesser extent (60 to 87%). The activation of all four hydrolases was inhibited by protein kinase inhibitor and reversed by the addition of exogenous protein kinase. Following activation by cAMP-dependent protein kinase, all four hydrolases were deactivated in a Mg2+-dependent reaction and then reactivated to or near initial levels on incubation with cAMP and Mg2+-ATP. The reversible deactivation is assumed to reflect activity of one or more protein phosphatases. The maximum activation obtainable for the four hydrolases decreased when the tissue had been previously exposed to glucagon, indicating that the glucagon-induced activation was probably similar to or identical with the activation demonstrated in cell-free preparations. The pH optima for the four hydrolase activities were similar (7.13 to 7.38). Although the absolute activities and relative degrees of kinase activation differed according to the particular emulsified substrates used, the results do not rule out the possibility that all four hydrolase activities are referable to a single hormone-sensitive hydrolase. Hormone-sensitive acyl hydrolases were separated from lipoprotein lipase by heparin-Sepharose affinity chromatography. Lipoprotein lipase was active against triolein, diolein, and monoolein, but not cholesterol oleate. Incubation of lipoprotein lipase with exogenous protein kinase, cAMP, and Mg2+ATP had no effect on any of the three hydrolase activities. Lipoprotein lipase was further purified to homogeneity and used to prepare antiserum in rabbits. The immunoglobin G fraction from these antisera completely inhibited lipoprotein lipase eluted from heparin-Sepharose columns. However, the hormone-sensitive hydrolase activities (not retained on heparin-Sepharose affinity chromatography) were not inhibited by anti-lipoprotein lipase immunoglobin G, and anti-lopoprotein lipase immunoglobin G did not affect the activation process in crude fractions. Thus, hormone-sensitive lipase and lipoprotein lipase, functionally distinct enzymes, have been physically resolved and immunochemically distinguished. Apparently lipoprotein lipase activity is not regulated, at least directly, by cAMP-dependent protein kinase."}
{"id": "PMID:5446", "title": "Binding studies of polypeptide hormones to bovine neurophysins.", "content": "Experimental binding isotherms of [9-glycinamide-1-(14)C]oxytocin and [9-glycinamide-1-(14)C]arginine vasopressin to purified neurophysins I and II at pH = 4.4, 5.4, 6.5, 7.4, and 8.5 and 6 degrees, 22 degrees, and 37 degrees in aqueous buffers are reported. For purposes of comparison, binding isotherms for [4-glycine-1-(14)C]oxytocin to neurophysin II and I in aqueous buffer, and [9-glycinamide-1-(14)C]oxytocin to neurophysin II in dimethylsulfoxide under selected conditions are also reported. A brief discussion of the interpretation of binding isotherms is entered into and apparent binding constants are derived. The results indicate that the interpretations presented in the literature up to now are much too simple. There are, in contrast, multiple binding sites of oxytocin and vasopressin to the neurophysins and large temperature dependences of the number of sites and their binding constants. We find, in fact, that at 37 degrees the binding of neurohypophysial hormones to the supposed storage proteins is rather weak even at the pH of maximum binding.", "contents": "Binding studies of polypeptide hormones to bovine neurophysins. Experimental binding isotherms of [9-glycinamide-1-(14)C]oxytocin and [9-glycinamide-1-(14)C]arginine vasopressin to purified neurophysins I and II at pH = 4.4, 5.4, 6.5, 7.4, and 8.5 and 6 degrees, 22 degrees, and 37 degrees in aqueous buffers are reported. For purposes of comparison, binding isotherms for [4-glycine-1-(14)C]oxytocin to neurophysin II and I in aqueous buffer, and [9-glycinamide-1-(14)C]oxytocin to neurophysin II in dimethylsulfoxide under selected conditions are also reported. A brief discussion of the interpretation of binding isotherms is entered into and apparent binding constants are derived. The results indicate that the interpretations presented in the literature up to now are much too simple. There are, in contrast, multiple binding sites of oxytocin and vasopressin to the neurophysins and large temperature dependences of the number of sites and their binding constants. We find, in fact, that at 37 degrees the binding of neurohypophysial hormones to the supposed storage proteins is rather weak even at the pH of maximum binding."}
{"id": "PMID:5447", "title": "Inhibition of bovine hepatic fructose-1,6-diphosphatase by substrate analogs.", "content": "Purified bovine hepatic fructose-1,6-diphosphatase, which exhibits maximal activity at neutral pH, is competitively inhibited by several analogs of its substrate, fructose 1,6-diphosphate. These include glucose 1,6-diphosphate (Ki = 9.4 X 10(-5) M), hexitol 1,6-diphosphate (Ki = 2.3 X 10(-4) M), and 2,5-anhydro-D-mannitol 1,6-diphosphate (Ki = 3.3 X 10(-8) M), and 2,5-anhydro-D-glucitol 1,6-diphosphate (Ki = 5.5 X 10(-7) M). The Ki values for both 2,5-anhydro-D-mannitol 1,6-diphosphate and 2,5-anhydro-D-glucitol 1,6-diphosphate are lower than the Km of 1.4 X 10(-6) M for fructose 1,6-diphosphate. Since 2,5-anhydro-D-mannitol 1,6-diphosphate is an analog of the beta anomer of fructose 1,6-diphosphate and 2,5-anhydro-D-glucitol 1,6-diphosphate is an analog of the alpha anomer, the lower Ki for the mannitol analog may indicate that the beta anomer of fructose 1,6-diphosphate, which predominates in solution, is the true substrate. The substrate analog 1,5-pentanediol diphosphate inhibits slightly (K0.5 = 5 X 10(-3) M), but 1,4-cyclohexyldiol diphosphate does not. The Ki for product inhibition by sodium phosphate is 9.4 X 10(-3) M. 2,5-Anhydro-D-mannitol 1,6-diphosphate and alpha-D-glucose 1,6-diphosphate are substrates at pH 9.0, but not at pH 6.5.", "contents": "Inhibition of bovine hepatic fructose-1,6-diphosphatase by substrate analogs. Purified bovine hepatic fructose-1,6-diphosphatase, which exhibits maximal activity at neutral pH, is competitively inhibited by several analogs of its substrate, fructose 1,6-diphosphate. These include glucose 1,6-diphosphate (Ki = 9.4 X 10(-5) M), hexitol 1,6-diphosphate (Ki = 2.3 X 10(-4) M), and 2,5-anhydro-D-mannitol 1,6-diphosphate (Ki = 3.3 X 10(-8) M), and 2,5-anhydro-D-glucitol 1,6-diphosphate (Ki = 5.5 X 10(-7) M). The Ki values for both 2,5-anhydro-D-mannitol 1,6-diphosphate and 2,5-anhydro-D-glucitol 1,6-diphosphate are lower than the Km of 1.4 X 10(-6) M for fructose 1,6-diphosphate. Since 2,5-anhydro-D-mannitol 1,6-diphosphate is an analog of the beta anomer of fructose 1,6-diphosphate and 2,5-anhydro-D-glucitol 1,6-diphosphate is an analog of the alpha anomer, the lower Ki for the mannitol analog may indicate that the beta anomer of fructose 1,6-diphosphate, which predominates in solution, is the true substrate. The substrate analog 1,5-pentanediol diphosphate inhibits slightly (K0.5 = 5 X 10(-3) M), but 1,4-cyclohexyldiol diphosphate does not. The Ki for product inhibition by sodium phosphate is 9.4 X 10(-3) M. 2,5-Anhydro-D-mannitol 1,6-diphosphate and alpha-D-glucose 1,6-diphosphate are substrates at pH 9.0, but not at pH 6.5."}
{"id": "PMID:5448", "title": "Genetic variants of human erythrocyte glucose-6-phosphate dehydrogenase. Kinetic and thermodynamic parameters of variants A, B, and A- in relation to quaternary structure.", "content": "The values of Vmax and Km for the three genetic variants A, B, and A- of erythrocyte glucose-6-phosphate dehydrogenase have been determined at 10 different pH values in the range from 5.5 to 9.5, and at four different temperatures in the range from 18.5-40.0 degrees. The log Vmax versus pH curve for each of the enzymes shows a monotonic increase between pH 5.5 and 7, and a plateau from pH 7.5 upwards. These curves, and their temperature dependence, are compatible with the presence of a single ionizable group which, in its conjugate acid form, renders the enzyme-substrate complex inactive. The pK of this group is 6.94 at 18.5 degrees, and its enthalpy of ionization is 7.0 kcal mol-1. The log Km versus pH curves show a broad plateau between pH 6.2 and 8.2, interrupted by a sharp minimum at pH 7.2 for variant B, while variants A and A- show sharp maxima at pH 7.2 and 7.45, respectively. It is proposed that this unusual behavior depends on the dissociation of the tetrameric enzyme to dimers in this pH region. Specifically, it is shown that  a sharp maximum or minimum of Km can arise if cooperative uptake or release of protons is linked to dimer formation, and if the degree of cooperativity is different for the free enzyme compared to the enzyme-substrate complex. The pH dependence of the equilibrium between the tetrameric and the dimeric form of the enzyme has been determined by gel filtration for the same three genetic variants B, A, and A-. In agreement with previous ultracentrifugal data, the enzyme is a tetramer in acid solution and a dimer in alkaline solution. The pH at which half of the enzyme is in dimeric form, under our experimental conditions, is 7.15 +/- 0.05 for variants A and B, and 7.35 +/- 0.05 for variant A-. These pH values correspond closely, for all three variants, to the sharp extrema in the pH dependence of their Km values for glucose 6-phosphate. From the measured dissociation equilibria, it can be inferred that the tetramer-dimer transition entails cooperative release of protons. The degree of cooperativity estimated from these data agrees closely with the independent estimate based on the pH dependence of Km.", "contents": "Genetic variants of human erythrocyte glucose-6-phosphate dehydrogenase. Kinetic and thermodynamic parameters of variants A, B, and A- in relation to quaternary structure. The values of Vmax and Km for the three genetic variants A, B, and A- of erythrocyte glucose-6-phosphate dehydrogenase have been determined at 10 different pH values in the range from 5.5 to 9.5, and at four different temperatures in the range from 18.5-40.0 degrees. The log Vmax versus pH curve for each of the enzymes shows a monotonic increase between pH 5.5 and 7, and a plateau from pH 7.5 upwards. These curves, and their temperature dependence, are compatible with the presence of a single ionizable group which, in its conjugate acid form, renders the enzyme-substrate complex inactive. The pK of this group is 6.94 at 18.5 degrees, and its enthalpy of ionization is 7.0 kcal mol-1. The log Km versus pH curves show a broad plateau between pH 6.2 and 8.2, interrupted by a sharp minimum at pH 7.2 for variant B, while variants A and A- show sharp maxima at pH 7.2 and 7.45, respectively. It is proposed that this unusual behavior depends on the dissociation of the tetrameric enzyme to dimers in this pH region. Specifically, it is shown that  a sharp maximum or minimum of Km can arise if cooperative uptake or release of protons is linked to dimer formation, and if the degree of cooperativity is different for the free enzyme compared to the enzyme-substrate complex. The pH dependence of the equilibrium between the tetrameric and the dimeric form of the enzyme has been determined by gel filtration for the same three genetic variants B, A, and A-. In agreement with previous ultracentrifugal data, the enzyme is a tetramer in acid solution and a dimer in alkaline solution. The pH at which half of the enzyme is in dimeric form, under our experimental conditions, is 7.15 +/- 0.05 for variants A and B, and 7.35 +/- 0.05 for variant A-. These pH values correspond closely, for all three variants, to the sharp extrema in the pH dependence of their Km values for glucose 6-phosphate. From the measured dissociation equilibria, it can be inferred that the tetramer-dimer transition entails cooperative release of protons. The degree of cooperativity estimated from these data agrees closely with the independent estimate based on the pH dependence of Km."}
{"id": "PMID:5449", "title": "Studies on tyrosine residues in porcine muscle adenylate kinase. Circular dichroism spectra and chemical modification with tetranitromethane.", "content": "Substrate-induced conformational change of porcine muscle adenylate kinase (EC 2.7.4.3) is evidenced by a change in circular dichroism spectra in the near ultraviolet. In the absence of tryptophan in porcine muscle adenylate kinase, the spectral change may be assigned to a perturbation of tyrosine chromophore(s). The spectral change was specific for adenine nucleotide binding and was greater with ATP than with AMP. In the x-ray model, Tyr153 and Tyr154 are located at a hinge region of two domains which form a deep active site cleft and are therefore susceptible to conformational change on substrate binding. Adenylate kinase was treated with equimolar tetranitromethane. The yellow-colored product, separated from unmodified enzyme by substrate gradient elution on a phosphocellulose column, had about 1 mol of nitrotyrosine per mol of the enzyme by amino acid analysis and showed a slightly higher Km value than native enzyme for ADP (Km = 0.50 mM compared with 0.25 mM for native adenylate kinase). Spectrophotometric titration of nitroadenylate kinase gave pKa 8.4 for the dissociation constant of the nitrotyrosyl hydroxyl group. On binding ATP the pKa value increased to 9.0 while AMP binding caused very little change. By peptide mapping of the carboxypeptidase digestion product, 0.70 mol of nitro group per mol of adenylate kinase was detected on Tyr153 and a small amount of nitro group was also found on Tyr95. From these results it is proposed that Tyr153 is directly or indirectly involved in the binding of ATP.", "contents": "Studies on tyrosine residues in porcine muscle adenylate kinase. Circular dichroism spectra and chemical modification with tetranitromethane. Substrate-induced conformational change of porcine muscle adenylate kinase (EC 2.7.4.3) is evidenced by a change in circular dichroism spectra in the near ultraviolet. In the absence of tryptophan in porcine muscle adenylate kinase, the spectral change may be assigned to a perturbation of tyrosine chromophore(s). The spectral change was specific for adenine nucleotide binding and was greater with ATP than with AMP. In the x-ray model, Tyr153 and Tyr154 are located at a hinge region of two domains which form a deep active site cleft and are therefore susceptible to conformational change on substrate binding. Adenylate kinase was treated with equimolar tetranitromethane. The yellow-colored product, separated from unmodified enzyme by substrate gradient elution on a phosphocellulose column, had about 1 mol of nitrotyrosine per mol of the enzyme by amino acid analysis and showed a slightly higher Km value than native enzyme for ADP (Km = 0.50 mM compared with 0.25 mM for native adenylate kinase). Spectrophotometric titration of nitroadenylate kinase gave pKa 8.4 for the dissociation constant of the nitrotyrosyl hydroxyl group. On binding ATP the pKa value increased to 9.0 while AMP binding caused very little change. By peptide mapping of the carboxypeptidase digestion product, 0.70 mol of nitro group per mol of adenylate kinase was detected on Tyr153 and a small amount of nitro group was also found on Tyr95. From these results it is proposed that Tyr153 is directly or indirectly involved in the binding of ATP."}
{"id": "PMID:5450", "title": "Antifreeze glycoproteins from Antarctic fish. Inactivation by borate.", "content": "Antifreeze glycoprotein, which has previously been shown to be inactive in the presence of borate, migrates electrophoretically as the borate complex, presumably through formation of borate complexes with hydroxyl groups on the sugar side chains. Antifreeze glycoprotein (5 mg/ml) has been found to be completely active in the presence of 0.1 M borate at pH 7, but inactive at pH 9. A titration curve of pH versus the antifreeze activity of glycoprotein (5 mg/ml) in 0.1 M borate showed a progressive decrease in antifreeze activity as the pH was increased. Concomitant with decreases in activity were increases in binding of borate. At pH 9.0, nearly 2 mol of borate were complexed per glycotripeptide. Ultracentrifuge analyses showed similar molecular weights and laser quasi-elastic light scattering showed similar diffusions at pH 7.0 and 9.0 in borate and in the absence of borate. The binding of borate, rather than a change in conformation, is thus directly related to the loss of antifreeze activity. Alkaline borate also decreased hemagglutinating activity of Osage orange lectin and decreased the inhibition of the activity by the antifreeze glycoproteins.", "contents": "Antifreeze glycoproteins from Antarctic fish. Inactivation by borate. Antifreeze glycoprotein, which has previously been shown to be inactive in the presence of borate, migrates electrophoretically as the borate complex, presumably through formation of borate complexes with hydroxyl groups on the sugar side chains. Antifreeze glycoprotein (5 mg/ml) has been found to be completely active in the presence of 0.1 M borate at pH 7, but inactive at pH 9. A titration curve of pH versus the antifreeze activity of glycoprotein (5 mg/ml) in 0.1 M borate showed a progressive decrease in antifreeze activity as the pH was increased. Concomitant with decreases in activity were increases in binding of borate. At pH 9.0, nearly 2 mol of borate were complexed per glycotripeptide. Ultracentrifuge analyses showed similar molecular weights and laser quasi-elastic light scattering showed similar diffusions at pH 7.0 and 9.0 in borate and in the absence of borate. The binding of borate, rather than a change in conformation, is thus directly related to the loss of antifreeze activity. Alkaline borate also decreased hemagglutinating activity of Osage orange lectin and decreased the inhibition of the activity by the antifreeze glycoproteins."}
{"id": "PMID:5451", "title": "Binding of (3H)prostaglandin E1 to putative receptors linked to adenylate cyclase of cultured cell clones.", "content": "A method for assessing the binding of 3H-labeled prostaglandin E1 ([3H]PGE1) to cell membranes has been developed and used to study the interaction of [3H]PGE1 with membranes from cultured mammalian cells. Receptor sites were identified by correlation of the potency of a series of compounds to compete for [3H]PGE1 binding sites and to stimulate adenylate cyclase activity, by correlation of rates of binding and change in enzyme activity, and by the correspondence of [3H]PGE1-binding activity with the presence or absence of PGE1-sensitive adenylate cyclase in several clones. In clone B82, a murine L-cell, [3H]PGE1 binds with an activation energy of 14 kcal/mol to a class of sites with an affinity of 0.5 X 10(8) M-1 and a capacity of 150 fmol/mg of protein. Concentration dependence of adenylate cyclase activation by PGE1 (KD =30 nM) and kinetic analysis of [3H]PGE1 binding (k1 = 4 X 10(6) liters/mol/min, k-1 0.15/min) verify this affinity. Concentration dependence and specificity of binding and activation of adenylate cyclases in neuroblastoma clone N4TG1 and N18TG2 substantiate the method. In several clones that lack PGE1-responsive adenylate cyclase, no specific [3H]PGE1 binding is detectable.", "contents": "Binding of (3H)prostaglandin E1 to putative receptors linked to adenylate cyclase of cultured cell clones. A method for assessing the binding of 3H-labeled prostaglandin E1 ([3H]PGE1) to cell membranes has been developed and used to study the interaction of [3H]PGE1 with membranes from cultured mammalian cells. Receptor sites were identified by correlation of the potency of a series of compounds to compete for [3H]PGE1 binding sites and to stimulate adenylate cyclase activity, by correlation of rates of binding and change in enzyme activity, and by the correspondence of [3H]PGE1-binding activity with the presence or absence of PGE1-sensitive adenylate cyclase in several clones. In clone B82, a murine L-cell, [3H]PGE1 binds with an activation energy of 14 kcal/mol to a class of sites with an affinity of 0.5 X 10(8) M-1 and a capacity of 150 fmol/mg of protein. Concentration dependence of adenylate cyclase activation by PGE1 (KD =30 nM) and kinetic analysis of [3H]PGE1 binding (k1 = 4 X 10(6) liters/mol/min, k-1 0.15/min) verify this affinity. Concentration dependence and specificity of binding and activation of adenylate cyclases in neuroblastoma clone N4TG1 and N18TG2 substantiate the method. In several clones that lack PGE1-responsive adenylate cyclase, no specific [3H]PGE1 binding is detectable."}
{"id": "PMID:5452", "title": "The mechanism of superoxide anion generation by the interaction of phenylhydrazine with hemoglobin.", "content": "The mechanism by which superoxide anion is generated by the interaction of phenylhydrazine with either oxy- or methemoglobin was investigated. Rather than superoxide anion generation resulting from an accelerated autooxidation of oxyhemoglobin, it was found that both oxy- and methemoglobin function as peroxidases toward phenylhydrazine with the resultant oxidation of this compound to phenyldiazine. Generation of phenyldiazine from the oxidation of phenylhydrazine by hemoglobin or by the hydrolysis and subsequent decarboxylation of methyl phenylazoformate (C6H5N=NCOOCH3) resulted in the production of superoxide anion. It is suggested that under certain conditions hemoglobin may function as a drug-metabolizing peroxidase.", "contents": "The mechanism of superoxide anion generation by the interaction of phenylhydrazine with hemoglobin. The mechanism by which superoxide anion is generated by the interaction of phenylhydrazine with either oxy- or methemoglobin was investigated. Rather than superoxide anion generation resulting from an accelerated autooxidation of oxyhemoglobin, it was found that both oxy- and methemoglobin function as peroxidases toward phenylhydrazine with the resultant oxidation of this compound to phenyldiazine. Generation of phenyldiazine from the oxidation of phenylhydrazine by hemoglobin or by the hydrolysis and subsequent decarboxylation of methyl phenylazoformate (C6H5N=NCOOCH3) resulted in the production of superoxide anion. It is suggested that under certain conditions hemoglobin may function as a drug-metabolizing peroxidase."}
{"id": "PMID:5453", "title": "Affinity labeling of a previously undetected essential lysyl residue in class I fructose bisphosphate aldolase.", "content": "The affinity label N-bromoacetylethanolamine phosphate (BrAcNHEtOP) has been used previously at pH 6.5 to identify His-359 of rabbit muscle aldolase as an active site residue. We now find that the specificity of the reagent is pH-dependent. At pH 8.5, alkylation with 14C-labeled BrAcNHEtOP abolishes both fructose-1,6-P2 cleavage activity and transaldolase activity. The stoichiometry of incorporation, the kinetics of inactivation, and the protection against inactivation afforded by a competitive inhibitor or dihydroxyacetone phosphate are consistent with the involvement of an active site residue. A comparison of 14C profiles obtained from chromatography on the amino acid analyzer of acid hydrolysates of inactivated and protected samples reveals that inactivation results from the alkylation of lysyl residues. The major peptide in tryptic digests of the inactivated enzyme has been isolated. Based on its amino acid composition and the known sequence of aldolase, Lys-146 is the residue preferentially alkylated by the reagent. Aldolase modified at His-359 is still subject to alkylation of lysine; thus Lys-146 and His-359 are not mutually exclusive sites. However, aldolase modified at Lys-146 is not subject to alkylation of histidine. One explanation of these observations is that modification of Lys-146 abolishes the binding capacity of aldolase for substrates and substrate analogs (BrAcNHEtOP), whereas modification of his-359 does not. Consistent with this explanation is the ability of aldolase modified at His-359 to form a Schiff base with substrate and the inability of aldolase modified at Lys-146 to do so. Therefore, Lys-146 could be one of the cationic groups that functions in electrostatic binding of the substrate's phosphate groups.", "contents": "Affinity labeling of a previously undetected essential lysyl residue in class I fructose bisphosphate aldolase. The affinity label N-bromoacetylethanolamine phosphate (BrAcNHEtOP) has been used previously at pH 6.5 to identify His-359 of rabbit muscle aldolase as an active site residue. We now find that the specificity of the reagent is pH-dependent. At pH 8.5, alkylation with 14C-labeled BrAcNHEtOP abolishes both fructose-1,6-P2 cleavage activity and transaldolase activity. The stoichiometry of incorporation, the kinetics of inactivation, and the protection against inactivation afforded by a competitive inhibitor or dihydroxyacetone phosphate are consistent with the involvement of an active site residue. A comparison of 14C profiles obtained from chromatography on the amino acid analyzer of acid hydrolysates of inactivated and protected samples reveals that inactivation results from the alkylation of lysyl residues. The major peptide in tryptic digests of the inactivated enzyme has been isolated. Based on its amino acid composition and the known sequence of aldolase, Lys-146 is the residue preferentially alkylated by the reagent. Aldolase modified at His-359 is still subject to alkylation of lysine; thus Lys-146 and His-359 are not mutually exclusive sites. However, aldolase modified at Lys-146 is not subject to alkylation of histidine. One explanation of these observations is that modification of Lys-146 abolishes the binding capacity of aldolase for substrates and substrate analogs (BrAcNHEtOP), whereas modification of his-359 does not. Consistent with this explanation is the ability of aldolase modified at His-359 to form a Schiff base with substrate and the inability of aldolase modified at Lys-146 to do so. Therefore, Lys-146 could be one of the cationic groups that functions in electrostatic binding of the substrate's phosphate groups."}
{"id": "PMID:5454", "title": "Purification and characterization of a repressible alkaline phosphatase from Thermus aquaticus.", "content": "A repressible alkaline phosphatase has been isolated from the extreme bacterial thermophile, Thermus aquaticus. The enzyme can be derepressed more than 1,000-fold by starving the cells for phosphate. In derepressed cells, nearly 6% of the total protein in a cell-free enzyme preparation is alkaline phosphatase. The enzyme was purified to homogeneity as judged by disc acrylamide electrophoresis and sodium dodecyl sulfate electrophoresis. By sucrose gradient centrifugation it was established that the enzyme has an approximate molecular weight of 143,000 and consists of three subunits, each with a molecular weight of 51,000. Tris buffer stimulates the activity of the enzyme, which has a pH optimum of 9.2. The enzyme has a broad temperature range with an optimum of 75-80 degrees. The enzyme catalyzes the hydrolysis of a wide variety of phosphorylated compounds as do many of the mesophilic alkaline phosphatases. The Michaelis constant(Km) for the enzyme is 8.0 X 10(-4) M. Amino acid analysis of the protein revealed little in the amino acid composition to separate it from other mesophilic enzymes which have been previously studied.", "contents": "Purification and characterization of a repressible alkaline phosphatase from Thermus aquaticus. A repressible alkaline phosphatase has been isolated from the extreme bacterial thermophile, Thermus aquaticus. The enzyme can be derepressed more than 1,000-fold by starving the cells for phosphate. In derepressed cells, nearly 6% of the total protein in a cell-free enzyme preparation is alkaline phosphatase. The enzyme was purified to homogeneity as judged by disc acrylamide electrophoresis and sodium dodecyl sulfate electrophoresis. By sucrose gradient centrifugation it was established that the enzyme has an approximate molecular weight of 143,000 and consists of three subunits, each with a molecular weight of 51,000. Tris buffer stimulates the activity of the enzyme, which has a pH optimum of 9.2. The enzyme has a broad temperature range with an optimum of 75-80 degrees. The enzyme catalyzes the hydrolysis of a wide variety of phosphorylated compounds as do many of the mesophilic alkaline phosphatases. The Michaelis constant(Km) for the enzyme is 8.0 X 10(-4) M. Amino acid analysis of the protein revealed little in the amino acid composition to separate it from other mesophilic enzymes which have been previously studied."}
{"id": "PMID:5455", "title": "Association of gylcogenolysis with cardiac sarcoplasmic reticulum.", "content": "Sarcoplasmic reticulum fragments isolated from dog cardiac muscle possess a calcium-accumulating system associated with a series of enzymes linked to glycogenolysis. These enzymes include: adenylate cyclase, cyclic AMP-dependent protein kinase, phosphorylase b kinase, phosphorylase (b/a, 30/1),\"debrancher\" enzyme, and glycogen (0.3 to 0.7 mg/mg of protein). The sarcoplasmic reticulum preparation produced glucose 1-phosphate and glucose from either endogenous or exogenous glycogen. Both the calcium-accumulating and glycogenolytic enzymes sediment in a single peak at 33% sucrose on a linear continous sucrose density gradient, and the complex remains intact throughout repeated washing. Glycogen particles appear to be associated with the sarcoplasmic reticulum in situ as well as in the isolated microsomal fraction. The sarcoplasmic reticulum-glycogenolytic complex, monitored by a linked enzyme spectrophotometric assay, shows several features: (a) activation of phosphorylase activity to peak rate occurs over a very rapid time course which cannot be duplicated using combinations of purified enzymes; (b) activation is inhibited by protein kinase inhibitor; (c) phosphorylase b functions as in the purified form with respect to AMP (Km, 0.3 mM); (d) in the presence of limiting amounts of glycogen, optimal phosphorylase b activity in the sarcoplasmic reticulum requires the presence of debrancher, and the activity is sensitive to inhibitors of that enzyme such as Tris, which suggests the possiblity that the enzymes bear a specific structual relationship to the glycogen present. Phosphorylase b leads to a activation in the sarcoplasmic reticulum was completely resistant to ethylene glycol bis(beta-aminoethyl either)-N,N'-tetraacetic acid (EGTA). Inhibition of calcium accumulation by or release of bound calcium from sarcoplasmic reticulum by X537A (RO 2-2985) did not alter the EGTA resistance. These results suggest that cardiac sarcoplasmic reticulum is a complex organelle containing functions that may be related to excitation-contraction coupling and intermediary metabolism.", "contents": "Association of gylcogenolysis with cardiac sarcoplasmic reticulum. Sarcoplasmic reticulum fragments isolated from dog cardiac muscle possess a calcium-accumulating system associated with a series of enzymes linked to glycogenolysis. These enzymes include: adenylate cyclase, cyclic AMP-dependent protein kinase, phosphorylase b kinase, phosphorylase (b/a, 30/1),\"debrancher\" enzyme, and glycogen (0.3 to 0.7 mg/mg of protein). The sarcoplasmic reticulum preparation produced glucose 1-phosphate and glucose from either endogenous or exogenous glycogen. Both the calcium-accumulating and glycogenolytic enzymes sediment in a single peak at 33% sucrose on a linear continous sucrose density gradient, and the complex remains intact throughout repeated washing. Glycogen particles appear to be associated with the sarcoplasmic reticulum in situ as well as in the isolated microsomal fraction. The sarcoplasmic reticulum-glycogenolytic complex, monitored by a linked enzyme spectrophotometric assay, shows several features: (a) activation of phosphorylase activity to peak rate occurs over a very rapid time course which cannot be duplicated using combinations of purified enzymes; (b) activation is inhibited by protein kinase inhibitor; (c) phosphorylase b functions as in the purified form with respect to AMP (Km, 0.3 mM); (d) in the presence of limiting amounts of glycogen, optimal phosphorylase b activity in the sarcoplasmic reticulum requires the presence of debrancher, and the activity is sensitive to inhibitors of that enzyme such as Tris, which suggests the possiblity that the enzymes bear a specific structual relationship to the glycogen present. Phosphorylase b leads to a activation in the sarcoplasmic reticulum was completely resistant to ethylene glycol bis(beta-aminoethyl either)-N,N'-tetraacetic acid (EGTA). Inhibition of calcium accumulation by or release of bound calcium from sarcoplasmic reticulum by X537A (RO 2-2985) did not alter the EGTA resistance. These results suggest that cardiac sarcoplasmic reticulum is a complex organelle containing functions that may be related to excitation-contraction coupling and intermediary metabolism."}
{"id": "PMID:5456", "title": "Purification and properties of a virion protein kinase.", "content": "The protein kinase associated with virions of frog virus 3 was purified to apparent homogeneity by ion exchange chromatography and gel filtration. The enzyme protein appeared as a single polypeptide of molecular weight 50,000 to 55,000 as determined by gel filtration, glycerol gradient sedimentation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and comprised approximately 0.4% of the total virion protein. The activity was classified as a cyclic nucleotide-independent protein kinase as it was not effected by cyclic adenosine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate, or inhibited by a cyclic nucleotide-dependent protein kinase inhibitor protein, and utilized GTP as well as ATP as a phosphate donor. The greatest rates of phosphorylation were obtained with acidic phosphoprotein substrates such as casein or phosvitin, although potential physiological substrates for this activity included specific virion polypeptides of frog virus.", "contents": "Purification and properties of a virion protein kinase. The protein kinase associated with virions of frog virus 3 was purified to apparent homogeneity by ion exchange chromatography and gel filtration. The enzyme protein appeared as a single polypeptide of molecular weight 50,000 to 55,000 as determined by gel filtration, glycerol gradient sedimentation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and comprised approximately 0.4% of the total virion protein. The activity was classified as a cyclic nucleotide-independent protein kinase as it was not effected by cyclic adenosine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate, or inhibited by a cyclic nucleotide-dependent protein kinase inhibitor protein, and utilized GTP as well as ATP as a phosphate donor. The greatest rates of phosphorylation were obtained with acidic phosphoprotein substrates such as casein or phosvitin, although potential physiological substrates for this activity included specific virion polypeptides of frog virus."}
{"id": "PMID:5457", "title": "The interaction of macromolecular solutions with macromolecular monolayers adsorbed on a hydrophobic surface.", "content": "In order to elucidate the general patterns of intermacromolecular surface interactions that may be involved in hemocompatibility phenomena, monolayers of representative macromolecules on an octadecylsilylated glass surface were exposed to solutions of other macromolecules, and the changes in interfacial composition were characterized by zeta potential-pH titration curves, as measured by alternating flow streaming current analysis and, in some cases, by radiotracer labeling. Experiments with poly(vinylpyrrolidone) (PVP), a blood-compatible linear polymer; bovine serum albumin (BSA), a representative serum protein; whole human serum (HS), a complex mixture of proteins; and erythrocyte surface glycoprotein (GP), an extended-chain macromolecular amphiphile, showed the following: 1) Penetration of the original monolayer occurred within 24 hr in 9 of the 12 possible cases; it did not occur for BSA or HS monolayers exposed to PVP, and probably not for PVP exposed to GP. 2) In all cases, penetration was accompanied by no more than partial displacement of the original monolayer, thereby generating a mixed monolayer. Each of the six possible binary mixed monolayers could be obtained by at least one of the two possible mixing sequences. 3) In the three binary systems containing BSA, the formation of the mixed monolayer could be related to increased adsorption in the two-component system. 4) The two components of the mixed monolayers were not equally distributed across their thicknesses: thus, the outer surfaces of the PVP-BSA and (at neutral pH) the PVP-HS mixed monolayers contained only PVP; that of the BSA-HS mixtures only HS. In the PVP-HS, and probably the GP-BSA and GP-HS mixed monolayers, the composition of the outer surface appeared pH-dependent. The resultant zeta potential versus pH profiles in the latter two cases resembled those of intact blood cells. The results suggest that neither the compact monolayers of globular proteins nor the diffuse monolayers of randomly coiled water-soluble polymers can, by their prior adsorption on a synthetic surface, prevent the subsequent adsorption of other globular macromolecules. It is possible that the randomly coiled polymers may impede the adhesion of platelets to the substrate since the results indicate that the adsorption of such polymers causes a displacement of the shear plane.", "contents": "The interaction of macromolecular solutions with macromolecular monolayers adsorbed on a hydrophobic surface. In order to elucidate the general patterns of intermacromolecular surface interactions that may be involved in hemocompatibility phenomena, monolayers of representative macromolecules on an octadecylsilylated glass surface were exposed to solutions of other macromolecules, and the changes in interfacial composition were characterized by zeta potential-pH titration curves, as measured by alternating flow streaming current analysis and, in some cases, by radiotracer labeling. Experiments with poly(vinylpyrrolidone) (PVP), a blood-compatible linear polymer; bovine serum albumin (BSA), a representative serum protein; whole human serum (HS), a complex mixture of proteins; and erythrocyte surface glycoprotein (GP), an extended-chain macromolecular amphiphile, showed the following: 1) Penetration of the original monolayer occurred within 24 hr in 9 of the 12 possible cases; it did not occur for BSA or HS monolayers exposed to PVP, and probably not for PVP exposed to GP. 2) In all cases, penetration was accompanied by no more than partial displacement of the original monolayer, thereby generating a mixed monolayer. Each of the six possible binary mixed monolayers could be obtained by at least one of the two possible mixing sequences. 3) In the three binary systems containing BSA, the formation of the mixed monolayer could be related to increased adsorption in the two-component system. 4) The two components of the mixed monolayers were not equally distributed across their thicknesses: thus, the outer surfaces of the PVP-BSA and (at neutral pH) the PVP-HS mixed monolayers contained only PVP; that of the BSA-HS mixtures only HS. In the PVP-HS, and probably the GP-BSA and GP-HS mixed monolayers, the composition of the outer surface appeared pH-dependent. The resultant zeta potential versus pH profiles in the latter two cases resembled those of intact blood cells. The results suggest that neither the compact monolayers of globular proteins nor the diffuse monolayers of randomly coiled water-soluble polymers can, by their prior adsorption on a synthetic surface, prevent the subsequent adsorption of other globular macromolecules. It is possible that the randomly coiled polymers may impede the adhesion of platelets to the substrate since the results indicate that the adsorption of such polymers causes a displacement of the shear plane."}
{"id": "PMID:5458", "title": "Stimulation of ornithine decarboxylase activity in chick fibroblasts by non-suppressible insulin-like activity (NSILA), insulin and serum.", "content": "A factor isolated from human serum (nonsuppressible insulin-like activity, NSILA) stimulates multiplication of serum-starved chick embryo fibroblasts and stimulates activity of ornithine decarboxylase (ODC). Physiological doses of NSILA (200 muU/ml) and pharmacological doses of insulin (200 mU/ml) stimulate ODC 4-5-fold, 10% fetal calf serum about 18-fold. Combined addition of NSILA and insulin does not result in higher activities, suggesting a common mechanism of action. The increase in cell number obtained with NSILA, insulin or serum parallels the degree of ODC stimulation. Treatment of cells with pronase also stimulates ODC activity. A sharp increase in ODC activity occurs between 2, 5 and 5.0 hours after addition of the growth factors with a peak at 4.0-4.5 hours (\"activation period\"). As cells leave G1 phase, ODC activity decreases rapidly. To achieve maximal activity of ODC, the growth factors have to be present during the entire \"activation period.\" The potential to reactivate ODC decreases as cells pass through S phase. Results obtained using cycloheximide suggest that ODC is translated only in the second half of the \"activation period.\" Data on effects of dbcAMP and dbcGMP on ODC activation by serum are discussed.", "contents": "Stimulation of ornithine decarboxylase activity in chick fibroblasts by non-suppressible insulin-like activity (NSILA), insulin and serum. A factor isolated from human serum (nonsuppressible insulin-like activity, NSILA) stimulates multiplication of serum-starved chick embryo fibroblasts and stimulates activity of ornithine decarboxylase (ODC). Physiological doses of NSILA (200 muU/ml) and pharmacological doses of insulin (200 mU/ml) stimulate ODC 4-5-fold, 10% fetal calf serum about 18-fold. Combined addition of NSILA and insulin does not result in higher activities, suggesting a common mechanism of action. The increase in cell number obtained with NSILA, insulin or serum parallels the degree of ODC stimulation. Treatment of cells with pronase also stimulates ODC activity. A sharp increase in ODC activity occurs between 2, 5 and 5.0 hours after addition of the growth factors with a peak at 4.0-4.5 hours (\"activation period\"). As cells leave G1 phase, ODC activity decreases rapidly. To achieve maximal activity of ODC, the growth factors have to be present during the entire \"activation period.\" The potential to reactivate ODC decreases as cells pass through S phase. Results obtained using cycloheximide suggest that ODC is translated only in the second half of the \"activation period.\" Data on effects of dbcAMP and dbcGMP on ODC activation by serum are discussed."}
{"id": "PMID:5459", "title": "Gas-liquid chromotographic determination of perazine, thioridazine and thioridazine metabolites in human plasma.", "content": "A gas-liquid chromatographic method for the detection of perazine, thioridazine and its major metabolites in human plasma is presented. Repeated extraction, an internal standard and a temperature program with flame ionization detection make possible accurate and reproducible results with patients on therapeutic doses of these drugs. Examples of chromatograms after extraction of plasma are given.", "contents": "Gas-liquid chromotographic determination of perazine, thioridazine and thioridazine metabolites in human plasma. A gas-liquid chromatographic method for the detection of perazine, thioridazine and its major metabolites in human plasma is presented. Repeated extraction, an internal standard and a temperature program with flame ionization detection make possible accurate and reproducible results with patients on therapeutic doses of these drugs. Examples of chromatograms after extraction of plasma are given."}
{"id": "PMID:5460", "title": "A reversed-phase thin-layer chromotographic method for the determination of relative partition coefficients of very lipophilic compounds.", "content": "A reversed-phase thin-layer chromatographic method has been developed for the determination of partition coefficients. A support phase has been chosen, following investigation of the lack of adsorptive properties, which has a minimal effect on the pH of the buffer system. A stationary phase has been chosen to give deltaRm values of the same magnitude as Hansch pi values for a series of phenothiazines. The method can be applied to molecules of a wide range of lipophilicity following preliminary investigations of suitable phase-volume ratios and of the pH and composition of the binary mobile phase, providing adsorption on the support phase is excluded.", "contents": "A reversed-phase thin-layer chromotographic method for the determination of relative partition coefficients of very lipophilic compounds. A reversed-phase thin-layer chromatographic method has been developed for the determination of partition coefficients. A support phase has been chosen, following investigation of the lack of adsorptive properties, which has a minimal effect on the pH of the buffer system. A stationary phase has been chosen to give deltaRm values of the same magnitude as Hansch pi values for a series of phenothiazines. The method can be applied to molecules of a wide range of lipophilicity following preliminary investigations of suitable phase-volume ratios and of the pH and composition of the binary mobile phase, providing adsorption on the support phase is excluded."}
{"id": "PMID:5461", "title": "High-pressure liquid chromatography of drugs. II. An evaluation of a microparticulate cation-exchange column.", "content": "A microparticulate cation-exchange column has been evaluated for the chromatography of thirty compounds selected as representative of a wide variety of drug substances. Although the column exhibited a strong partition effect besides the expected ion-exchange mechanism, the retention of drugs could be predictably influenced by variation of the eluent ionic strength and organic solvent content. For acidic drugs the column showed little selectivity (although a salting-out effect increased retention at high eluent ionic strengths), but for basic substances Partisil SCX may afford a useful separative medium offering reasonable chromatographic efficiency (HETP is approximately 0.1 mm). The column longevity, however, is at present questionable.", "contents": "High-pressure liquid chromatography of drugs. II. An evaluation of a microparticulate cation-exchange column. A microparticulate cation-exchange column has been evaluated for the chromatography of thirty compounds selected as representative of a wide variety of drug substances. Although the column exhibited a strong partition effect besides the expected ion-exchange mechanism, the retention of drugs could be predictably influenced by variation of the eluent ionic strength and organic solvent content. For acidic drugs the column showed little selectivity (although a salting-out effect increased retention at high eluent ionic strengths), but for basic substances Partisil SCX may afford a useful separative medium offering reasonable chromatographic efficiency (HETP is approximately 0.1 mm). The column longevity, however, is at present questionable."}
{"id": "PMID:5462", "title": "Resolution in affinity chromatography. The effect of the heterogeneity of immobilized soybean trypsin inhibitor on the separation of pancreatic proteases.", "content": "By affinity chromatography, trypsins and chymotrypsins from mouse pancreas homogenates have been separated using soybean trypsin inhibitor immobilized on Sepharose. The effects of the functional heterogeneity of the adsorbent have been investigated in terms of the resolution obtained. Heterogeneity of the adsorbent have been investigated in terms of the resolution obtained. Heterogeneity has been found to originate from the following sources: heterogeneity of the ligand before immobilization; alteration of the ligand by immobilization; and modification of the ligand after immobilization by molecules to be fractionated. Only when the heterogeneity of the adsorbent was minimized could the resolution of closely related enzyme species be achieved. The elution conditions for different enzymes depended on the amount of enzyme applied, as no complete homogeneity could be obtained. In addition, it was found that the adsorbent was partly degraded by the pancreas extract, reducing its fractionating capacity.", "contents": "Resolution in affinity chromatography. The effect of the heterogeneity of immobilized soybean trypsin inhibitor on the separation of pancreatic proteases. By affinity chromatography, trypsins and chymotrypsins from mouse pancreas homogenates have been separated using soybean trypsin inhibitor immobilized on Sepharose. The effects of the functional heterogeneity of the adsorbent have been investigated in terms of the resolution obtained. Heterogeneity of the adsorbent have been investigated in terms of the resolution obtained. Heterogeneity has been found to originate from the following sources: heterogeneity of the ligand before immobilization; alteration of the ligand by immobilization; and modification of the ligand after immobilization by molecules to be fractionated. Only when the heterogeneity of the adsorbent was minimized could the resolution of closely related enzyme species be achieved. The elution conditions for different enzymes depended on the amount of enzyme applied, as no complete homogeneity could be obtained. In addition, it was found that the adsorbent was partly degraded by the pancreas extract, reducing its fractionating capacity."}
{"id": "PMID:5463", "title": "A thin-layer chromatographic method for the determination of acebutolol and its major metabolite in serum.", "content": "A sensitive and specific thin-layer chromatographic method for the simultaneous determination of acebutolol [DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane] and its major metabolite [DL-1-(2-acetyl-4-acetamidophenoxy)-2-hydroxy-3-isopropylaminopropane] is described. A 2-ml volume of serum with 350 ng of quinidine as internal standard was extracted at pH 10, the solvent was evaporated off and the residue was dissolved in 50 mul of methanol. A 10-mul volume of the solution was spotted on a thin-layer plate and after elution (ethyl acetate-methanol-ammonia, 75:20:5) the plate was dried at 90 for 15 min and, after cooling, dipped in a 10% paraffin wax solution. The fluorescence was measured using a spectrofluorimeter with a thin-layer scanning attachment. The peak-height ratios of acebutolol to internal standard and metabolite to internal standard were used to quantitate acebutolol and the metabolite, respectively.", "contents": "A thin-layer chromatographic method for the determination of acebutolol and its major metabolite in serum. A sensitive and specific thin-layer chromatographic method for the simultaneous determination of acebutolol [DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane] and its major metabolite [DL-1-(2-acetyl-4-acetamidophenoxy)-2-hydroxy-3-isopropylaminopropane] is described. A 2-ml volume of serum with 350 ng of quinidine as internal standard was extracted at pH 10, the solvent was evaporated off and the residue was dissolved in 50 mul of methanol. A 10-mul volume of the solution was spotted on a thin-layer plate and after elution (ethyl acetate-methanol-ammonia, 75:20:5) the plate was dried at 90 for 15 min and, after cooling, dipped in a 10% paraffin wax solution. The fluorescence was measured using a spectrofluorimeter with a thin-layer scanning attachment. The peak-height ratios of acebutolol to internal standard and metabolite to internal standard were used to quantitate acebutolol and the metabolite, respectively."}
{"id": "PMID:5465", "title": "Influence of L-prolyl-L-leucyl-glycine amide on growth hormone secretion in normal and acromegalic subjects.", "content": "Melanocyte Release-Inhibiting Peptide (MRIP-I) did not affect circulating levels of ACTH, LH, FSH, TSH,ORL, betaMSH and insulin when iv infused (5.0 mg in 5 min plus 0.4 mg/min for 70-115 min), while it significantly reduced serum GH response to hypoglycemia in normal subjects and lowered serum GH levels in acromegalics. There was no correlation between the fall in serum GH after MRIP and after dopaminergic drugs in acromegaly. These data are compatible with either a direct suppressive action exerted by MRIP-I at pituitary level or an extra-pituitary effect not involving dopaminergic pathways. It can be spec-lated that since labelled MRIP-I accumualtes in the pineal and melatonin blunts GH response to hypoglycemia, the pineal gland might be involved in the MRIP-I-induced suppression of GH secretion.", "contents": "Influence of L-prolyl-L-leucyl-glycine amide on growth hormone secretion in normal and acromegalic subjects. Melanocyte Release-Inhibiting Peptide (MRIP-I) did not affect circulating levels of ACTH, LH, FSH, TSH,ORL, betaMSH and insulin when iv infused (5.0 mg in 5 min plus 0.4 mg/min for 70-115 min), while it significantly reduced serum GH response to hypoglycemia in normal subjects and lowered serum GH levels in acromegalics. There was no correlation between the fall in serum GH after MRIP and after dopaminergic drugs in acromegaly. These data are compatible with either a direct suppressive action exerted by MRIP-I at pituitary level or an extra-pituitary effect not involving dopaminergic pathways. It can be spec-lated that since labelled MRIP-I accumualtes in the pineal and melatonin blunts GH response to hypoglycemia, the pineal gland might be involved in the MRIP-I-induced suppression of GH secretion."}
{"id": "PMID:5466", "title": "Use of Counter and rocket immunoelectrophoresis in acute respiratory infections due to Streptococcus pneumoniae.", "content": "The use of Counter immunoelectrophoresis (CIE) for the detection of pneumococcal capsular antigen in the sputum and serum of patients suffering from acute respiratory infections is described. The CIE of sputum gave positive results in 224 (99%) out of 225 samples in which Streptococcus pneumoniae was isolated by cultural techniques, and in 23 (9%) out of 262 samples in which no or other potential pathogens had been isolated. In the detection of capsular antigen in serum, CIE was positive in 32 (35%) out of 92 pneumonia cases and was associated with an increase in mortality.", "contents": "Use of Counter and rocket immunoelectrophoresis in acute respiratory infections due to Streptococcus pneumoniae. The use of Counter immunoelectrophoresis (CIE) for the detection of pneumococcal capsular antigen in the sputum and serum of patients suffering from acute respiratory infections is described. The CIE of sputum gave positive results in 224 (99%) out of 225 samples in which Streptococcus pneumoniae was isolated by cultural techniques, and in 23 (9%) out of 262 samples in which no or other potential pathogens had been isolated. In the detection of capsular antigen in serum, CIE was positive in 32 (35%) out of 92 pneumonia cases and was associated with an increase in mortality."}
{"id": "PMID:5467", "title": "Requirement for a macromolecular factor for sodium azide activation of guanulate cyclase.", "content": "Sodium azide, a highly nucleophilic agent and a potent metabolic inhibitor, markedly increased guanylate cyclase activity from supernatant fractions of rat liver homogenates. The effect of sodium azide was not observed with partially purified guanulate cyclase from liver or crude soluble guanylate cyclase from cerebral cortex. However, the effect of sodium azide could be restored by the readdition of a fraction isolated from rat liver homogenates. The macromolecular factor required for the sodium azide effect was separated from soluble guanylate cyclase of rat liver with DEAE-cellulose column chromatography, and some of its properties were examined. The factor was nondialyzable and heat labile.", "contents": "Requirement for a macromolecular factor for sodium azide activation of guanulate cyclase. Sodium azide, a highly nucleophilic agent and a potent metabolic inhibitor, markedly increased guanylate cyclase activity from supernatant fractions of rat liver homogenates. The effect of sodium azide was not observed with partially purified guanulate cyclase from liver or crude soluble guanylate cyclase from cerebral cortex. However, the effect of sodium azide could be restored by the readdition of a fraction isolated from rat liver homogenates. The macromolecular factor required for the sodium azide effect was separated from soluble guanylate cyclase of rat liver with DEAE-cellulose column chromatography, and some of its properties were examined. The factor was nondialyzable and heat labile."}
{"id": "PMID:5469", "title": "A rapid method for the assay of guanylate cyclase.", "content": "An extremely rapid and sensitive assay for guanylate cyclase utilizing [alpha-32P]-GTP has been developed. It involves incubation of 5-100 mug of enzyme protein with 1 mM [alpha-32P]-GTP in 40 mM Tris HC1 buffer (pH 7.4) containing 3-3 mM MnSO2, 10 mM theophylline and 1 mM cyclic GMP. The reaction is terminated by addition of EDTA, and [32P]-cyclic GMP formed is isolated by sequential chromatography on Dowex-50-H+ and alumina. Recovery of 75-85% of [3H]-cyclic GMP and a blank of 0.001-0.003% of added [32P]-GTP was routinely obtained. The [32P] radioactivity isolated was shown to be cyclic GMP by a variety of techniques. The assay has also been shown to be applicable for a variety of tissues.", "contents": "A rapid method for the assay of guanylate cyclase. An extremely rapid and sensitive assay for guanylate cyclase utilizing [alpha-32P]-GTP has been developed. It involves incubation of 5-100 mug of enzyme protein with 1 mM [alpha-32P]-GTP in 40 mM Tris HC1 buffer (pH 7.4) containing 3-3 mM MnSO2, 10 mM theophylline and 1 mM cyclic GMP. The reaction is terminated by addition of EDTA, and [32P]-cyclic GMP formed is isolated by sequential chromatography on Dowex-50-H+ and alumina. Recovery of 75-85% of [3H]-cyclic GMP and a blank of 0.001-0.003% of added [32P]-GTP was routinely obtained. The [32P] radioactivity isolated was shown to be cyclic GMP by a variety of techniques. The assay has also been shown to be applicable for a variety of tissues."}
{"id": "PMID:5468", "title": "Lysosomal enzyme secretion from human neutrophils mediated by cyclic CMP: inhibition of cyclic GMP accumulation and neutrophil function by glucocorticosteroids.", "content": "The effects of several glucocorticosteroids on cyclic GMP accumulation, guanylate cyclase activity, calcium influx, lysosomal enzyme secretion, and phagocytosis were studied in human neutrophils. Contact between neutrophils and serum-treated zymosan particles, in the presence of calcium at pH 7.4, triggered these cellular events within five minutes. Each of these neutrophil functions was markedly inhibited by methylprednisolone sodium succinate, triamcinolone acetonide hemisuccinate and paramethasone acetate but was unaffected by two mineralo-corticosteroids. Human neutrophil soluble guanylate cyclase activity was not changed by the glucocorticoids. Inhibition of phagocytosis by, and lysosomal enzyme secretion from, neutrophils by glucocorticosteroids may be the result of a reduction in cyclic GMP accumulation within these cells. The data suggest that glucocorticosteroids inhibit cyclic GMP accumulation in neutrophils by reducing the influx of extracellular calcium into the cells, thereby limiting the availability of intracellular calcium for metabolic processes associated with the accumulation of cyclic GMP.", "contents": "Lysosomal enzyme secretion from human neutrophils mediated by cyclic CMP: inhibition of cyclic GMP accumulation and neutrophil function by glucocorticosteroids. The effects of several glucocorticosteroids on cyclic GMP accumulation, guanylate cyclase activity, calcium influx, lysosomal enzyme secretion, and phagocytosis were studied in human neutrophils. Contact between neutrophils and serum-treated zymosan particles, in the presence of calcium at pH 7.4, triggered these cellular events within five minutes. Each of these neutrophil functions was markedly inhibited by methylprednisolone sodium succinate, triamcinolone acetonide hemisuccinate and paramethasone acetate but was unaffected by two mineralo-corticosteroids. Human neutrophil soluble guanylate cyclase activity was not changed by the glucocorticoids. Inhibition of phagocytosis by, and lysosomal enzyme secretion from, neutrophils by glucocorticosteroids may be the result of a reduction in cyclic GMP accumulation within these cells. The data suggest that glucocorticosteroids inhibit cyclic GMP accumulation in neutrophils by reducing the influx of extracellular calcium into the cells, thereby limiting the availability of intracellular calcium for metabolic processes associated with the accumulation of cyclic GMP."}
{"id": "PMID:5470", "title": "Cyclic AMP content and regulation of tyrosine-3-mono-oxygenase in rat striatum.", "content": "The unilateral transection of nigro striatal dopaminergic axons produced a short lasting (15-30 min) increase in the affinity of striatal tyrosine 3-mono-oxygenase (TH), for a synthetic pteridine cofactor (DMPH4). The kinetic changes of striatal TH were paralleled by an increase of striatal cAMP content. Apomorphine (10 mg/kg i.p.) failed to block the activation of TH by cerebral hemisection. Haloperidol (5 mg/kg i.p.) and reserpine (5 mg/kg i.p.) also elicited a sudden and similar change in striatal TH activity but this response occurred without an increase in the cAMP content and lasted for longer than 2 hrs. If the hemisection of nigrostriatal pathway was performed after haloperidol or reserpine injection the activation of TH produced by these two drugs was reversed rapidly (about 30 minutes). Pretreatment with haloperidol or reserpine prevented the increase of striatal cAMP following cerebral hemisection. Moreover, haloperidol injected 30 min after cerebral hemisection failed to change the TH kinetic properties in the striatum ipsilateral to the lesion but it changed striatal TH in the side contralateral to the lesion. These results suggest that the increase in the affinity of striatal TH for the pteridine cofactor elicited by cerebral hemisection is not related to a lack of stimulation  of DA autoreceptors. Moreover these experiments provide an  evidence that postsynaptic dopamine receptors play a role in the activation of striatal TH elicited by haloperidol.", "contents": "Cyclic AMP content and regulation of tyrosine-3-mono-oxygenase in rat striatum. The unilateral transection of nigro striatal dopaminergic axons produced a short lasting (15-30 min) increase in the affinity of striatal tyrosine 3-mono-oxygenase (TH), for a synthetic pteridine cofactor (DMPH4). The kinetic changes of striatal TH were paralleled by an increase of striatal cAMP content. Apomorphine (10 mg/kg i.p.) failed to block the activation of TH by cerebral hemisection. Haloperidol (5 mg/kg i.p.) and reserpine (5 mg/kg i.p.) also elicited a sudden and similar change in striatal TH activity but this response occurred without an increase in the cAMP content and lasted for longer than 2 hrs. If the hemisection of nigrostriatal pathway was performed after haloperidol or reserpine injection the activation of TH produced by these two drugs was reversed rapidly (about 30 minutes). Pretreatment with haloperidol or reserpine prevented the increase of striatal cAMP following cerebral hemisection. Moreover, haloperidol injected 30 min after cerebral hemisection failed to change the TH kinetic properties in the striatum ipsilateral to the lesion but it changed striatal TH in the side contralateral to the lesion. These results suggest that the increase in the affinity of striatal TH for the pteridine cofactor elicited by cerebral hemisection is not related to a lack of stimulation  of DA autoreceptors. Moreover these experiments provide an  evidence that postsynaptic dopamine receptors play a role in the activation of striatal TH elicited by haloperidol."}
{"id": "PMID:5471", "title": "Properties of guanylate cyclase from rat kidney cortex and transplantable kidney tumors.", "content": "The subcellular distribution and properties of guanylate cyclase was examined in preparations of normal rat renal cortex and Morris renal tumors MK2 and MK3. In normal kidney cortex about two-thirds of guanylate cyclase activity of homogenates was found in soluble fractions. With renal tumors the homogenate activity was less and the enzyme was equally divided between particulate and soluble fractions. The particulate enzyme in kidney cortex and tumors was associated with all particulate fractions. Triton X-100 increased the activity of all preparations. All preparations preferred Mn2+ as the sole cation. The stimulatory effects of Ca2+ on soluble enzyme and inhibitory effects on particulate activity were similar with preparations of renal cortex and tumors. ATP inhibited all preparations. Soluble and particulate guanylate cyclases from renal cortex were activated several-fold with 1 mM NaN3. Preparations of tumor enzymes did not respond to NaN3. Thus, compared to normal renal cortex the subcellular distribution of guanylate cyclase and some of its properties are altered in preparations of renal tumors.", "contents": "Properties of guanylate cyclase from rat kidney cortex and transplantable kidney tumors. The subcellular distribution and properties of guanylate cyclase was examined in preparations of normal rat renal cortex and Morris renal tumors MK2 and MK3. In normal kidney cortex about two-thirds of guanylate cyclase activity of homogenates was found in soluble fractions. With renal tumors the homogenate activity was less and the enzyme was equally divided between particulate and soluble fractions. The particulate enzyme in kidney cortex and tumors was associated with all particulate fractions. Triton X-100 increased the activity of all preparations. All preparations preferred Mn2+ as the sole cation. The stimulatory effects of Ca2+ on soluble enzyme and inhibitory effects on particulate activity were similar with preparations of renal cortex and tumors. ATP inhibited all preparations. Soluble and particulate guanylate cyclases from renal cortex were activated several-fold with 1 mM NaN3. Preparations of tumor enzymes did not respond to NaN3. Thus, compared to normal renal cortex the subcellular distribution of guanylate cyclase and some of its properties are altered in preparations of renal tumors."}
{"id": "PMID:5472", "title": "Reduction of enamel solubility by sodium monophosphate.", "content": "The preponderance of evidence indicates that sodium monofluorophosphate exerts a highly beneficial effect on dental caries incidence and enamel solubility. Optimal effects are obtained with a concentration of 4 X 10(3) ppm fluoride, by a four-minute application and by adjusting the pH to 4.0. The reaction of sodium monofluorophosphate with enamel is not temperature dependent. Sodium monofluorophosphate is significantly more protective than sodium fluoride in aqueous solutions at all equivalent fluoride concentrations and in pastes at concentrations exceeding 8 X 10(3) ppm fluoride.", "contents": "Reduction of enamel solubility by sodium monophosphate. The preponderance of evidence indicates that sodium monofluorophosphate exerts a highly beneficial effect on dental caries incidence and enamel solubility. Optimal effects are obtained with a concentration of 4 X 10(3) ppm fluoride, by a four-minute application and by adjusting the pH to 4.0. The reaction of sodium monofluorophosphate with enamel is not temperature dependent. Sodium monofluorophosphate is significantly more protective than sodium fluoride in aqueous solutions at all equivalent fluoride concentrations and in pastes at concentrations exceeding 8 X 10(3) ppm fluoride."}
{"id": "PMID:5478", "title": "Proxemics, locus of control, anxiety, and type of movement in emotionally disturbed and normal boys.", "content": "In order to determine the interpersonal distancing requirements for emotionally disturbed and normal children and in order to investigate the relationship of locus of control and anxiety to interpersonal space, 20 emotionally disturbed and 20 normal boys were randomly required to approach an object person and to let the object person approach them until they felt uncomfortable. Results indicated that emotionally disturbed boys required more space than normals; that subjects would approach closer than they would allow the object person to approach them; and that externals required more space than internals. There were no significant differences between high and low anxious subjects, nor between emotionally disturbed children diagnostically classified as overanxious reaction and those with other diagnosis. Finally, neither anxiety nor locus of control explained the significant normal-emotionally disturbed differences in space requirements. Theoretical and practical implications were discussed as well as the relationship between the present and previous research.", "contents": "Proxemics, locus of control, anxiety, and type of movement in emotionally disturbed and normal boys. In order to determine the interpersonal distancing requirements for emotionally disturbed and normal children and in order to investigate the relationship of locus of control and anxiety to interpersonal space, 20 emotionally disturbed and 20 normal boys were randomly required to approach an object person and to let the object person approach them until they felt uncomfortable. Results indicated that emotionally disturbed boys required more space than normals; that subjects would approach closer than they would allow the object person to approach them; and that externals required more space than internals. There were no significant differences between high and low anxious subjects, nor between emotionally disturbed children diagnostically classified as overanxious reaction and those with other diagnosis. Finally, neither anxiety nor locus of control explained the significant normal-emotionally disturbed differences in space requirements. Theoretical and practical implications were discussed as well as the relationship between the present and previous research."}
{"id": "PMID:5482", "title": "Pharmacotherapy in older depressed patients.", "content": "Treatment of depression in elderly patients is not generically different from treatment of depression in younger age cohorts. Because of certain age-related physical, physiological, and biochemical factors, however, drug prescription for geriatric patients must be modified in several respects. Tricyclic antidepressants are the principal agents in treatment, but their side effects tend to be magnified in the elderly. Dosage should initially be lower than with younger patients and increased in gradual increments. Lithium, MAO inhibitors, and neuroleptics are appropriate in some cases, but additional precautions are necessary. Because the elderly are liable to multiple system decompensation, they are likely to be prescribed multiple pharmacological agents. Drug-drug interactions involving antidepressant medication present a variety of therapeutic problems and can threaten life. Depression in late life can be treated pharmacologically, but both the therapeutic and deleterious activities of the drugs can be altered by compromised organ systems.", "contents": "Pharmacotherapy in older depressed patients. Treatment of depression in elderly patients is not generically different from treatment of depression in younger age cohorts. Because of certain age-related physical, physiological, and biochemical factors, however, drug prescription for geriatric patients must be modified in several respects. Tricyclic antidepressants are the principal agents in treatment, but their side effects tend to be magnified in the elderly. Dosage should initially be lower than with younger patients and increased in gradual increments. Lithium, MAO inhibitors, and neuroleptics are appropriate in some cases, but additional precautions are necessary. Because the elderly are liable to multiple system decompensation, they are likely to be prescribed multiple pharmacological agents. Drug-drug interactions involving antidepressant medication present a variety of therapeutic problems and can threaten life. Depression in late life can be treated pharmacologically, but both the therapeutic and deleterious activities of the drugs can be altered by compromised organ systems."}
{"id": "PMID:5560", "title": "The binding of complement by complexes formed between a rabbit antibody and oligosaccharides of increasing size.", "content": "Immune complexes formed between a homogeneous rabbit antibody to type III pneumococcal polysaccharide and a series of oligosaccharides of varying size derived from it were prepared and tested for their ability to fix guinea pig hemolytic complement. Antibody and either tetra-, hexa-, or octasaccharide formed only monomeric antibody-hapten complexes and did not show any complement binding. A dodecasaccharide and a 16-sugar residues oligomer formed dimer and trimer immune complexes. These complexes were also unable to fix complement. However, as the size of the sugar oligomers was increased to about 21 sugar residues per oligosaccharide molecule or more, the resulting complexes exhibited substantial complement binding, concomitant with the formation of antigen-antibody aggregates higher than trimers. On the other hand, an independent study carried out with the same material suggested changes in the conformation of the Fc moiety in the antibody molecule upon addition of oligosaccharide ligands as small as a 16-residue unit. Since the resulting complexes hardly ehibited any complement binding, ligand-induced conformational changes in the Fc part of the antibody molecule appears to be an insufficient condition per se for triggering complement fixation.", "contents": "The binding of complement by complexes formed between a rabbit antibody and oligosaccharides of increasing size. Immune complexes formed between a homogeneous rabbit antibody to type III pneumococcal polysaccharide and a series of oligosaccharides of varying size derived from it were prepared and tested for their ability to fix guinea pig hemolytic complement. Antibody and either tetra-, hexa-, or octasaccharide formed only monomeric antibody-hapten complexes and did not show any complement binding. A dodecasaccharide and a 16-sugar residues oligomer formed dimer and trimer immune complexes. These complexes were also unable to fix complement. However, as the size of the sugar oligomers was increased to about 21 sugar residues per oligosaccharide molecule or more, the resulting complexes exhibited substantial complement binding, concomitant with the formation of antigen-antibody aggregates higher than trimers. On the other hand, an independent study carried out with the same material suggested changes in the conformation of the Fc moiety in the antibody molecule upon addition of oligosaccharide ligands as small as a 16-residue unit. Since the resulting complexes hardly ehibited any complement binding, ligand-induced conformational changes in the Fc part of the antibody molecule appears to be an insufficient condition per se for triggering complement fixation."}
{"id": "PMID:5561", "title": "Neonatal infection with mouse thymic virus: effects on cells regulating the antibody response to type III pneumococcal polysaccharide.", "content": "Mice infected neonatally with mouse thymic virus (TA) were evaluated at different ages with respect to their ability to give a plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III), as well as the degree of amplifier and suppressor thymus-derived (T) cell activity present. B cell activity matured rapidly from 2 to 4 weeks of age and was not affected by TA infection. Amplifier T cell activity matured progressively over the first 8 weeks of life and was transiently suppressed in TA-infected mice at 4 weeks of age. Suppressor T cell activity measured at 2,4, and 6 weeks of age was unaffected by TA. The findings suggest that TA is highly tropic for T cells and has selective effects on subpopulations of T cells.", "contents": "Neonatal infection with mouse thymic virus: effects on cells regulating the antibody response to type III pneumococcal polysaccharide. Mice infected neonatally with mouse thymic virus (TA) were evaluated at different ages with respect to their ability to give a plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III), as well as the degree of amplifier and suppressor thymus-derived (T) cell activity present. B cell activity matured rapidly from 2 to 4 weeks of age and was not affected by TA infection. Amplifier T cell activity matured progressively over the first 8 weeks of life and was transiently suppressed in TA-infected mice at 4 weeks of age. Suppressor T cell activity measured at 2,4, and 6 weeks of age was unaffected by TA. The findings suggest that TA is highly tropic for T cells and has selective effects on subpopulations of T cells."}
{"id": "PMID:5483", "title": "The chromosomes of four species of the nasuta complex of Drosophila. I. Chromosome maps and inversion polymorphism.", "content": "The salivary chromosomes of four species of the nasuta complex of Drosophila, D. sulfurigaster albostrigata, D, kohkoa, D. albomicans, and D. kepulauana were studied and chromosome maps of each species are presented; the maps of the latter three species are based on the map of D. sulfurigaster albostrigata. Three of the species D. sulfurigaster albostrigata, D. albomicans, and D. kohkoa were shown to be highly polymorphic for chromosomal inversions while the available evidence indicated that D. kepulauana is much less polymorphic. These facts are correlated with the geographic distribution of the species. Transitional homoselection has not been complete in the evolution of three of the species since D. sulfurigaster albostrigata, D. kohkoa, and D. albomicans have a number of naturally occurring polymorphisms in common.", "contents": "The chromosomes of four species of the nasuta complex of Drosophila. I. Chromosome maps and inversion polymorphism. The salivary chromosomes of four species of the nasuta complex of Drosophila, D. sulfurigaster albostrigata, D, kohkoa, D. albomicans, and D. kepulauana were studied and chromosome maps of each species are presented; the maps of the latter three species are based on the map of D. sulfurigaster albostrigata. Three of the species D. sulfurigaster albostrigata, D. albomicans, and D. kohkoa were shown to be highly polymorphic for chromosomal inversions while the available evidence indicated that D. kepulauana is much less polymorphic. These facts are correlated with the geographic distribution of the species. Transitional homoselection has not been complete in the evolution of three of the species since D. sulfurigaster albostrigata, D. kohkoa, and D. albomicans have a number of naturally occurring polymorphisms in common."}
{"id": "PMID:5562", "title": "Graft-vs-host reactions in F1 mice induced by parental lymphoid cells: nature of recruited F1 cells.", "content": "Graft versus host (GVH) reactivity of parental lymph node (LN) cells was assayed by measurements of 3H-thymidine incorporation in vivo. Mitomycin (Mit.) treatment of parental cells abolished their proliferative activity but the combination of such Mit.-treated parental cells with F1 LN cells resulted in much higher proliferation than either one population alone. This recruitment into proliferation of F1 cells was prominent on days 3 and 4 after cell injection and amounted to 35 to 51% of the total activity seen after injection of untreated parental cells alone. The F1 cell sensitive to recruitment was resistant to anti-Thy 1.2 treatment, was not removed by carbonyl iron-magnet separation; and was not present in thymus. The parental cell inducing recruitment was, however, sensitive to anti-Thy 1.2. When spleen cells from hapten immune F1 donors were injected together with Mit.-treated parental LN cells and boosted with hapten on another carrier, a typical \"allogeneic effect\" was observed in the anti-hapten immune response. It was concluded that Mit.-treated parental T cells exerted a mitogenic effect on F1 B cells resulting in extensive recruitment similar to that seen in murine mixed lymphocyte reactions.", "contents": "Graft-vs-host reactions in F1 mice induced by parental lymphoid cells: nature of recruited F1 cells. Graft versus host (GVH) reactivity of parental lymph node (LN) cells was assayed by measurements of 3H-thymidine incorporation in vivo. Mitomycin (Mit.) treatment of parental cells abolished their proliferative activity but the combination of such Mit.-treated parental cells with F1 LN cells resulted in much higher proliferation than either one population alone. This recruitment into proliferation of F1 cells was prominent on days 3 and 4 after cell injection and amounted to 35 to 51% of the total activity seen after injection of untreated parental cells alone. The F1 cell sensitive to recruitment was resistant to anti-Thy 1.2 treatment, was not removed by carbonyl iron-magnet separation; and was not present in thymus. The parental cell inducing recruitment was, however, sensitive to anti-Thy 1.2. When spleen cells from hapten immune F1 donors were injected together with Mit.-treated parental LN cells and boosted with hapten on another carrier, a typical \"allogeneic effect\" was observed in the anti-hapten immune response. It was concluded that Mit.-treated parental T cells exerted a mitogenic effect on F1 B cells resulting in extensive recruitment similar to that seen in murine mixed lymphocyte reactions."}
{"id": "PMID:5563", "title": "Determinants of red cell sickling. Effects of varying pH and of increasing intracellular hemoglobin concentration by osmotic shrinkage.", "content": "The effects of varying pH and of increasing intracellular hemoglobin (Hb) concentration on red cell sickling and oxygen affinity were studied in whole blood from persons with sickle cell anemia (SS) and sickle cell trait (SA). Small increases in SS blood pH inhibited sickling, and small reductions in both SS and SA blood pH promoted sickling far more than accounted for by the Bohr effect. Sickling behavior correlated with minimum gelling concentrations (MGC) of deoxygenated hemolysates without 2,3-diphosphoglycerate. MGC values fell sharply when pH was lowered from 7.25 to 7.15 for HbS and from 7.15 to 6.90 for SA hemolysates, suggesting effects on specific ionic interactions involved in Hb gelation. Possible clinical counterparts are acute metabolic acidosis and alkalosis (prior to change in red cell 2,3-diphosphoglycerate), where the Bohr effect and oxygen affinity-independent effects of pH alterations on sickling would be additive. Osmotic shrinkage of HbS-containing red cells produced a large fall in oxygen affinity and a marked increase in sickling independent of that fall. The oxygen affinity and sickling properties of SA cells whose MCHC was raised to 40 per cent resembled those of unaltered SS cells, supporting a relationship between molecular aggregation of Hb and low oxygen affinity. Sickling of aerated SS cells in hypertonic saline depended upon partial Hb desaturation due to lowered oxygen affinity. Thus osmotic shrinkage of HbS-containing cells acts synergistically with partial deoxygenation to promote sickling. These conditions are present in the renal medulla, but may occur elsewhere in severe hyperosmolar states.", "contents": "Determinants of red cell sickling. Effects of varying pH and of increasing intracellular hemoglobin concentration by osmotic shrinkage. The effects of varying pH and of increasing intracellular hemoglobin (Hb) concentration on red cell sickling and oxygen affinity were studied in whole blood from persons with sickle cell anemia (SS) and sickle cell trait (SA). Small increases in SS blood pH inhibited sickling, and small reductions in both SS and SA blood pH promoted sickling far more than accounted for by the Bohr effect. Sickling behavior correlated with minimum gelling concentrations (MGC) of deoxygenated hemolysates without 2,3-diphosphoglycerate. MGC values fell sharply when pH was lowered from 7.25 to 7.15 for HbS and from 7.15 to 6.90 for SA hemolysates, suggesting effects on specific ionic interactions involved in Hb gelation. Possible clinical counterparts are acute metabolic acidosis and alkalosis (prior to change in red cell 2,3-diphosphoglycerate), where the Bohr effect and oxygen affinity-independent effects of pH alterations on sickling would be additive. Osmotic shrinkage of HbS-containing red cells produced a large fall in oxygen affinity and a marked increase in sickling independent of that fall. The oxygen affinity and sickling properties of SA cells whose MCHC was raised to 40 per cent resembled those of unaltered SS cells, supporting a relationship between molecular aggregation of Hb and low oxygen affinity. Sickling of aerated SS cells in hypertonic saline depended upon partial Hb desaturation due to lowered oxygen affinity. Thus osmotic shrinkage of HbS-containing cells acts synergistically with partial deoxygenation to promote sickling. These conditions are present in the renal medulla, but may occur elsewhere in severe hyperosmolar states."}
{"id": "PMID:5564", "title": "Bacterial interference as a factor in renal infection.", "content": "These experiments have investigated the role of bacterial interference as a determinant in the epidemiology of renal infection. Two unrelated strains of Escherichia coli, E. coli 08 and 075, isolated from cases of clinical pyelonephritis were used. Although both strains had identical morphology on conventional media they could be differentiated using genetically stable markers for streptomycin resistance and arabinose utilization. When the 2 strains of E. coli were introduced into the kidney simultaneously by direct inoculation mixed infections were readily established. On the other hand, although both strains of E. coli were equally invasive as individual pathogens, pyelonephritis, when induced using a retrograde challenge with a mixed culture of the same organisms was almost invariably caused by the 08 strain alone. Further experiments showed that bacterial interference occurred within the kidney and determined the pattern of infection. When unilateral renal infections were established with E. coli 08 and the animals subsequently challenged with E. coli 075, it was found that E. coli 075 infection never occurred in kidneys infected with E. coli 08 but infection was established in the contralateral kidney. The experiments have shown that mixed renal infection with E. coli are uncommon even when both pathogens are equally nephropathogenic and are introduced simultaneously into the bladder.", "contents": "Bacterial interference as a factor in renal infection. These experiments have investigated the role of bacterial interference as a determinant in the epidemiology of renal infection. Two unrelated strains of Escherichia coli, E. coli 08 and 075, isolated from cases of clinical pyelonephritis were used. Although both strains had identical morphology on conventional media they could be differentiated using genetically stable markers for streptomycin resistance and arabinose utilization. When the 2 strains of E. coli were introduced into the kidney simultaneously by direct inoculation mixed infections were readily established. On the other hand, although both strains of E. coli were equally invasive as individual pathogens, pyelonephritis, when induced using a retrograde challenge with a mixed culture of the same organisms was almost invariably caused by the 08 strain alone. Further experiments showed that bacterial interference occurred within the kidney and determined the pattern of infection. When unilateral renal infections were established with E. coli 08 and the animals subsequently challenged with E. coli 075, it was found that E. coli 075 infection never occurred in kidneys infected with E. coli 08 but infection was established in the contralateral kidney. The experiments have shown that mixed renal infection with E. coli are uncommon even when both pathogens are equally nephropathogenic and are introduced simultaneously into the bladder."}
{"id": "PMID:5565", "title": "The effect of the plasma bicarbonate level on proximal tubule sodium reabsorption in NH4Cl-loaded dogs.", "content": "In an attempt to examine the effects of mild and severe chronic metabolic acidosis on proximal tubule sodium reabsorption, 6 dogs were given 10 mEq. per kilogram per day and 5 dogs were given 20mEq. per kilogram per day of ammonium chloride for 3 days and compared to 12 normal dogs during a steady-state water diuresis and following the administration of ethacrynic acid (EA) intravenously (2 mg. per kilogram) utilizing standard clearance methodology, In the severely acidotic group (pH decrease is greater tthan 0.2) plasma pH was 7.08 +/- 0.06 and plasma bicarbonate was 6.3 +/- 1.0 Eq. per liter compared to a pH of 7.33 +/-0.02 and bicarbonate of 13.4 +/- 0.7 in mild acidosis (pH decrease is less than 0.2). During a steady-state water diuresis urine flow was 14.2 +/- 0.9 in severely acidotic compared to 10.5 +/-0.7 ml. per minute per 100 ml. glomerular filtration rate (GFR) in normal dogs (p is less than 0.01). Following EA sodium clearance increased 38.4 +/- 3.5 in severely acidotic dogs and 27.6 +/- 2.0 ml. per minute per 100 ml. GFR in normal dogs (p is less than 0.02). In mild acidosis, steady-state fractional urine flow and the increase in fractional sodium clearance following EA were not significantly different than normal dogs. We conclude that chronic metabolic acidosis leads to an increase in distal solute load and enhanced natriuretic effect of EA secondary to a decrease in proximal tubule sodium reabsorption which may be dependent upon the degree of reduction in the plasma bicarbonate level.", "contents": "The effect of the plasma bicarbonate level on proximal tubule sodium reabsorption in NH4Cl-loaded dogs. In an attempt to examine the effects of mild and severe chronic metabolic acidosis on proximal tubule sodium reabsorption, 6 dogs were given 10 mEq. per kilogram per day and 5 dogs were given 20mEq. per kilogram per day of ammonium chloride for 3 days and compared to 12 normal dogs during a steady-state water diuresis and following the administration of ethacrynic acid (EA) intravenously (2 mg. per kilogram) utilizing standard clearance methodology, In the severely acidotic group (pH decrease is greater tthan 0.2) plasma pH was 7.08 +/- 0.06 and plasma bicarbonate was 6.3 +/- 1.0 Eq. per liter compared to a pH of 7.33 +/-0.02 and bicarbonate of 13.4 +/- 0.7 in mild acidosis (pH decrease is less than 0.2). During a steady-state water diuresis urine flow was 14.2 +/- 0.9 in severely acidotic compared to 10.5 +/-0.7 ml. per minute per 100 ml. glomerular filtration rate (GFR) in normal dogs (p is less than 0.01). Following EA sodium clearance increased 38.4 +/- 3.5 in severely acidotic dogs and 27.6 +/- 2.0 ml. per minute per 100 ml. GFR in normal dogs (p is less than 0.02). In mild acidosis, steady-state fractional urine flow and the increase in fractional sodium clearance following EA were not significantly different than normal dogs. We conclude that chronic metabolic acidosis leads to an increase in distal solute load and enhanced natriuretic effect of EA secondary to a decrease in proximal tubule sodium reabsorption which may be dependent upon the degree of reduction in the plasma bicarbonate level."}
{"id": "PMID:5566", "title": "Lethal midline granuloma: a pathological spectrum.", "content": "Lethal midline granuloma is a non-specific clinical term used for different pathological entities often exhibiting some semblance to each other as they lie along a histological spectrum. Nevertheless, each entity has a specific diagnostic pattern. The histological picture with distinguishing features of each specific type is pointed out. Stress is made on the use of repeated biopsy until the specific histological diagnosis can be made so that specific treatment as breifly outlined, can be carried out to insure the best prognosis.", "contents": "Lethal midline granuloma: a pathological spectrum. Lethal midline granuloma is a non-specific clinical term used for different pathological entities often exhibiting some semblance to each other as they lie along a histological spectrum. Nevertheless, each entity has a specific diagnostic pattern. The histological picture with distinguishing features of each specific type is pointed out. Stress is made on the use of repeated biopsy until the specific histological diagnosis can be made so that specific treatment as breifly outlined, can be carried out to insure the best prognosis."}
{"id": "PMID:5567", "title": "Ganglioside biosynthesis. Characterization of uridine diphosphate galactose: GM2 galactosyltransferase in golgi apparatus from rat liver.", "content": "An enzyme that transfers galactose from UDP-Gal to ganglioside GM2 (Tay-Sachs ganglioside) was concentrated 50 times in Golgi apparatus from rat liver relative to total homogenates. This enzyme required detergents or phospholipids as dispersing agents. Of the numerous detergents tested, sodium taurocholate and Triton CF-54 were most effective in stimulating the reaction. Cardiolipin alone was more effective than any of the detergents tested in stimulating enzyme activity. The pH optimum for the reaction varied with the nature of the dispersing agent. With sodium taurocholate, Triton CF-54 and cardiolipin, the pH optima were 6.2, 5.9, and 5.6, respectively. The enzyme had a nearly absolute requirement for Mn2+, with maximum activity being attained at a concentration of 15 mM Mn2+. Other divalent or trivalent cations were either less effective than Mn2+ or inhibited the transferase reaction. The Km values calculated for UDP-Gal and GM2 were 1.1 X 10(-4) M and 9.9 X 10(-5) M, respectively. The enzyme could not be dissociated from Golgi apparatus fractions by treatment with ultrasound, indicating that it is tightly associated with the membrane and not part of the luminal contents. The newly synthesized GM2, the product of the reaction, was incorporated into or became tightly associated with the membranes of the Golgi apparatus.", "contents": "Ganglioside biosynthesis. Characterization of uridine diphosphate galactose: GM2 galactosyltransferase in golgi apparatus from rat liver. An enzyme that transfers galactose from UDP-Gal to ganglioside GM2 (Tay-Sachs ganglioside) was concentrated 50 times in Golgi apparatus from rat liver relative to total homogenates. This enzyme required detergents or phospholipids as dispersing agents. Of the numerous detergents tested, sodium taurocholate and Triton CF-54 were most effective in stimulating the reaction. Cardiolipin alone was more effective than any of the detergents tested in stimulating enzyme activity. The pH optimum for the reaction varied with the nature of the dispersing agent. With sodium taurocholate, Triton CF-54 and cardiolipin, the pH optima were 6.2, 5.9, and 5.6, respectively. The enzyme had a nearly absolute requirement for Mn2+, with maximum activity being attained at a concentration of 15 mM Mn2+. Other divalent or trivalent cations were either less effective than Mn2+ or inhibited the transferase reaction. The Km values calculated for UDP-Gal and GM2 were 1.1 X 10(-4) M and 9.9 X 10(-5) M, respectively. The enzyme could not be dissociated from Golgi apparatus fractions by treatment with ultrasound, indicating that it is tightly associated with the membrane and not part of the luminal contents. The newly synthesized GM2, the product of the reaction, was incorporated into or became tightly associated with the membranes of the Golgi apparatus."}
{"id": "PMID:5568", "title": "Effect on various putative neurotransmitters on the secretion of corticotrophin-releasing hormone from the rat hypothalamus in vitro-a model of the neurotransmitters involved.", "content": "The effect of incubating the hypothalamus of adult male rats with various neurotransmitters upon the release of corticotrophin-releasing hormone (CRH) was studied. The CRH activity in the incubation medium was assayed in 48 h median eminence-lesioned rats and the corticosteroidogenesis of excised adrenals in vitro was used as the end-point. 5-Hydroxytryptamine (100 pg/ml-10ng/ml) caused a dose-dependent release of CRH which was antagonized by methysergide (30-100 ng/ml). The response to 5-hydroxytryptamine was also inhibited by hexamethonium and atropine which indicated that it was acting through a cholinergic interneurone. Melatonin (10 ng) did not alter the basal release of CRH but inhibited the action of both 5-hydroxytryptamine (10 ng) and acetylcholine (3 pg). Thus it appears that both 5-hydroxytryptamine and melatonin play a role in the control of CRH release. Noradrenaline blocked the release of CRH induced by both acetylcholine and 5-hydroxytryptamine and presumably this inhibition was caused by direct action on the CRH neurone. gamma-Aminobutyric acid (GABA) also inhibited the release of CRH and may also be involved in the regulation of CRH secretion. The inhibitory neurotransmitters, noradrenaline, GABA and melatonin, act via independent receptor mechanisms. A model based on the above data is presented.", "contents": "Effect on various putative neurotransmitters on the secretion of corticotrophin-releasing hormone from the rat hypothalamus in vitro-a model of the neurotransmitters involved. The effect of incubating the hypothalamus of adult male rats with various neurotransmitters upon the release of corticotrophin-releasing hormone (CRH) was studied. The CRH activity in the incubation medium was assayed in 48 h median eminence-lesioned rats and the corticosteroidogenesis of excised adrenals in vitro was used as the end-point. 5-Hydroxytryptamine (100 pg/ml-10ng/ml) caused a dose-dependent release of CRH which was antagonized by methysergide (30-100 ng/ml). The response to 5-hydroxytryptamine was also inhibited by hexamethonium and atropine which indicated that it was acting through a cholinergic interneurone. Melatonin (10 ng) did not alter the basal release of CRH but inhibited the action of both 5-hydroxytryptamine (10 ng) and acetylcholine (3 pg). Thus it appears that both 5-hydroxytryptamine and melatonin play a role in the control of CRH release. Noradrenaline blocked the release of CRH induced by both acetylcholine and 5-hydroxytryptamine and presumably this inhibition was caused by direct action on the CRH neurone. gamma-Aminobutyric acid (GABA) also inhibited the release of CRH and may also be involved in the regulation of CRH secretion. The inhibitory neurotransmitters, noradrenaline, GABA and melatonin, act via independent receptor mechanisms. A model based on the above data is presented."}
{"id": "PMID:5569", "title": "Purification of canine prolactin by preparative isotachophoresis.", "content": "Preparative isotachophoresis in polyacrylamide gel using carrier ampholytes as 'spacers' has been used to purify prolactin from canine pituitary extracts. Using Ampholine pH 5-8 as spacers, a prolactin fraction was obtained which was essentially homogeneous as judged by the criteria of disc electrophoresis and isoelectric focusing. Amino acid analysis indicated a close similarity between canine and ovine prolactin. A growth hormone fraction, identified by its electrophoretic mobility, was also obtained although this was heterogeneous in disc electrophoresis at alkaline pH.", "contents": "Purification of canine prolactin by preparative isotachophoresis. Preparative isotachophoresis in polyacrylamide gel using carrier ampholytes as 'spacers' has been used to purify prolactin from canine pituitary extracts. Using Ampholine pH 5-8 as spacers, a prolactin fraction was obtained which was essentially homogeneous as judged by the criteria of disc electrophoresis and isoelectric focusing. Amino acid analysis indicated a close similarity between canine and ovine prolactin. A growth hormone fraction, identified by its electrophoretic mobility, was also obtained although this was heterogeneous in disc electrophoresis at alkaline pH."}
{"id": "PMID:5570", "title": "Acid-base balance in rainbow trout (Salmo gairdneri) subjected to acid stresses.", "content": "1. The respiratory properties of rainbow-trout blood were investigated in acid-stressed fish. In the first group acid was introduced into the bloodstream and in the second the carbon dioxide content of the ambient water was increased. 2. Initially the introduction of acid to the blood caused a decrease in blood pH and bicarbonate, and increases in oxygen uptake and ventilation volume. After 2-3 h these values had returned to the control levels. 3. Trout subjected to high ambient CO2 (about 10 mmHg) showed a decrease in blood pH while PCO2 and bicarbonate increased. After 8 h the trout began to show signs of compensation to the acidosis. 4. In each experiment the blood PO2 was little changed but blood O2 content was decreased and tended not to resume the control value even after several hours. 5. The results are discussed in terms of the various acid-base mechanisms thought to be available to the fish. These include branchial ion exchanges and the possible buffering roles of the extracellular and intracellular fluids.", "contents": "Acid-base balance in rainbow trout (Salmo gairdneri) subjected to acid stresses. 1. The respiratory properties of rainbow-trout blood were investigated in acid-stressed fish. In the first group acid was introduced into the bloodstream and in the second the carbon dioxide content of the ambient water was increased. 2. Initially the introduction of acid to the blood caused a decrease in blood pH and bicarbonate, and increases in oxygen uptake and ventilation volume. After 2-3 h these values had returned to the control levels. 3. Trout subjected to high ambient CO2 (about 10 mmHg) showed a decrease in blood pH while PCO2 and bicarbonate increased. After 8 h the trout began to show signs of compensation to the acidosis. 4. In each experiment the blood PO2 was little changed but blood O2 content was decreased and tended not to resume the control value even after several hours. 5. The results are discussed in terms of the various acid-base mechanisms thought to be available to the fish. These include branchial ion exchanges and the possible buffering roles of the extracellular and intracellular fluids."}
{"id": "PMID:5571", "title": "Connexions between hair-plate afferents and motoneurones in the cockroach leg.", "content": "1. The trochanteral hair-plate afferents in the metathoracic leg of the cockroach, Periplaneta americana, were stimulated electrically and at the same time intracellular recordings were made from either motoneurones, interneurones or afferent terminals within the methathoracic ganglion. 2. Activity in the hair-plate afferents evoked short latency excitatory postsynaptic potentials (EPSPs) in femur flexor motoneurones. The latency of the IPSPs was on average 1-8 ms longer than the latency ofthe EPSPs. 3. Intracellular recordings from terminal branches of the hair-plate afferents showed that the delay between the peak of the afferent terminal spike and the beginning of the EPSPs is about 0.4 ms. This finding, together with the observations that the amplitude of the EPSPs is increased by the passage of hyperpolarizing current and decreased following high-frequency stimulation, indicates that the EPpSPs are evoked via-monosynaptic chemical synaptic junctions. 4. The observations of the long latency of the IPSPs, the need for a number of afferents to be simultaneously acive for them to be evoked and the occasional variability in latency, all indicate that the IPSPs are evoked via a disynaptic pathway...", "contents": "Connexions between hair-plate afferents and motoneurones in the cockroach leg. 1. The trochanteral hair-plate afferents in the metathoracic leg of the cockroach, Periplaneta americana, were stimulated electrically and at the same time intracellular recordings were made from either motoneurones, interneurones or afferent terminals within the methathoracic ganglion. 2. Activity in the hair-plate afferents evoked short latency excitatory postsynaptic potentials (EPSPs) in femur flexor motoneurones. The latency of the IPSPs was on average 1-8 ms longer than the latency ofthe EPSPs. 3. Intracellular recordings from terminal branches of the hair-plate afferents showed that the delay between the peak of the afferent terminal spike and the beginning of the EPSPs is about 0.4 ms. This finding, together with the observations that the amplitude of the EPSPs is increased by the passage of hyperpolarizing current and decreased following high-frequency stimulation, indicates that the EPpSPs are evoked via-monosynaptic chemical synaptic junctions. 4. The observations of the long latency of the IPSPs, the need for a number of afferents to be simultaneously acive for them to be evoked and the occasional variability in latency, all indicate that the IPSPs are evoked via a disynaptic pathway..."}
{"id": "PMID:5572", "title": "Physiological properties of eel haemoglobin: hypoxic acclimation, phosphate effects and multiplicity.", "content": "Unlike the whole body oxygen affinity, which adapts readily to environmental oxygen tensions, haemoglobins, prepared from normoxic- and hypoxic-accimated eels (Anguilla anguilla) show no adaptive changes in oxygenation properties or in multiplicity. Hypoxic acclimation is, howeveer, accompanied by a strong decrease in red cell nucleoside triphosphates, particularly guanosine triphospphate (GTP), which depresses oxygen affinity of the composite and component haemoglobins more strongly than does the concurring ATP. The effects of pH, temperature and salts on the oxygenation properties of the (isolated) haemoglobins are reported, discussed in relation to the varying environmetal conditions encountered by eels, and compared with data on American and Japanese eels (A. rostrata and A. juponica, respectively.", "contents": "Physiological properties of eel haemoglobin: hypoxic acclimation, phosphate effects and multiplicity. Unlike the whole body oxygen affinity, which adapts readily to environmental oxygen tensions, haemoglobins, prepared from normoxic- and hypoxic-accimated eels (Anguilla anguilla) show no adaptive changes in oxygenation properties or in multiplicity. Hypoxic acclimation is, howeveer, accompanied by a strong decrease in red cell nucleoside triphosphates, particularly guanosine triphospphate (GTP), which depresses oxygen affinity of the composite and component haemoglobins more strongly than does the concurring ATP. The effects of pH, temperature and salts on the oxygenation properties of the (isolated) haemoglobins are reported, discussed in relation to the varying environmetal conditions encountered by eels, and compared with data on American and Japanese eels (A. rostrata and A. juponica, respectively."}
{"id": "PMID:5573", "title": "[LP-X in newborns: increased incidence of positive tests without cholestasis (author's transl)].", "content": "The investigation of 194 newborns has shown that during the first weeks of life the abnormal lipoprotein-X (LP-X) was present in the serum of nearly 50% of the infants, with no clinical chemical evidence of cholestasis. The percentage of LP-X positive tests was even higher in the group of immature newborns (65%). There was no correlation between the bilirubin concentration and the detection of LP-X. The activities of leucine arylamidase (EC 3.4.1.1) and gamma-glutamyltransferase (EC 2.3.2.2) as well as the concentrations of total and free cholesterol did not differ in the LP-X positive and negative infants. Except in one case, LP-X was never detectable on the first day of life. The earliest date of appearance was the second day. In the serum of some infants, who were LP-X positive shortly after birth, the lipoprotein could still be found at the age of 2--3 months. The incidence of LP-X was not higher in newborns with blood group incompatibility than in newborns with unspecific hyperbilirubinaemia. After exchange transfusions LP-X disappeared in most cases, but it could later often be detected again. In some newborns, who were LP-X negative a few days after birth LP-X was first detected at the age of 2-3 months. The LP-X test is of no use for th diagnosis of cholestasis in newborn infants. The test is specific for cholestasis only after the first year of life. The increased incidence of positive LP-X tests in newborns is discussed as a consequence of immature liver function.", "contents": "[LP-X in newborns: increased incidence of positive tests without cholestasis (author's transl)]. The investigation of 194 newborns has shown that during the first weeks of life the abnormal lipoprotein-X (LP-X) was present in the serum of nearly 50% of the infants, with no clinical chemical evidence of cholestasis. The percentage of LP-X positive tests was even higher in the group of immature newborns (65%). There was no correlation between the bilirubin concentration and the detection of LP-X. The activities of leucine arylamidase (EC 3.4.1.1) and gamma-glutamyltransferase (EC 2.3.2.2) as well as the concentrations of total and free cholesterol did not differ in the LP-X positive and negative infants. Except in one case, LP-X was never detectable on the first day of life. The earliest date of appearance was the second day. In the serum of some infants, who were LP-X positive shortly after birth, the lipoprotein could still be found at the age of 2--3 months. The incidence of LP-X was not higher in newborns with blood group incompatibility than in newborns with unspecific hyperbilirubinaemia. After exchange transfusions LP-X disappeared in most cases, but it could later often be detected again. In some newborns, who were LP-X negative a few days after birth LP-X was first detected at the age of 2-3 months. The LP-X test is of no use for th diagnosis of cholestasis in newborn infants. The test is specific for cholestasis only after the first year of life. The increased incidence of positive LP-X tests in newborns is discussed as a consequence of immature liver function."}
{"id": "PMID:5574", "title": "Neurotrophic activity of brain extracts in forelimb regeneration of the urodele, Triturus.", "content": "The loss in protein synthesis which the regenerating forelimb of the newt suffers after denervation can be recovered by infusing into it an extract of newt soluble brain protein. Moreover, the synthesis of basic protein shows a greater response to the active brain principle than does that of acidic protein. The active agent of the nervous tissue is destroyed by heat and trypsin digestion. Extracts of liver and spleen, similarly prepared, do not evoke recovery of lost protein synthesis. Synaptosomal extracts of the frog brain also cause recovery of protein synthesis in the denervated regenerate, demonstrating the likelihood that the active agent is not species-specific within these amphibians, that it is a constituent of the neuronal fraction of nervous tissue, and that it is present in axonal terminals. Additional experiments showed that the nervous agent is likely a basic protein, and that the amount of protein infused is of the order of only 1.0% of the total regenerate protein. The significance of the findings is discussed in relation to the nature of the effect on protein synthesis and the nature of the active principle.", "contents": "Neurotrophic activity of brain extracts in forelimb regeneration of the urodele, Triturus. The loss in protein synthesis which the regenerating forelimb of the newt suffers after denervation can be recovered by infusing into it an extract of newt soluble brain protein. Moreover, the synthesis of basic protein shows a greater response to the active brain principle than does that of acidic protein. The active agent of the nervous tissue is destroyed by heat and trypsin digestion. Extracts of liver and spleen, similarly prepared, do not evoke recovery of lost protein synthesis. Synaptosomal extracts of the frog brain also cause recovery of protein synthesis in the denervated regenerate, demonstrating the likelihood that the active agent is not species-specific within these amphibians, that it is a constituent of the neuronal fraction of nervous tissue, and that it is present in axonal terminals. Additional experiments showed that the nervous agent is likely a basic protein, and that the amount of protein infused is of the order of only 1.0% of the total regenerate protein. The significance of the findings is discussed in relation to the nature of the effect on protein synthesis and the nature of the active principle."}
{"id": "PMID:5575", "title": "Interaction between phloretin and the red blood cell membrane.", "content": "Phloretin binding to red blood cell components has been characterized at pH6, where binding and inhibitory potency are maximal. Binding to intact red cells and to purified hemoglobin are nonsaturated processes approximately equal in magnitude, which strongly suggests that most of the red cell binding may be ascribed to hemoglobin. This conclusion is supported by the fact that homoglobin-free red cell ghosts can bind only 10% as much phloretin as an equivalent number of red cells. The permeability of the red cell membrane to phloretin has been determined by a direct measurement at the time-course of the phloretin uptake. At a 2% hematocrit, the half time for phloretin uptake is 8.7s, corresponding to a permeability coefficient of 2 x 10(-4) cm/s. The concentration dependence of the binding to ghosts reveals two saturable components. Phloretin binds with high affinity (K diss = 1.5 muM) to about 2.5 x 10(6) sites per cell; it also binds with lower affinity (Kdiss = 54 muM) to a second (5.5 x 10(7) per cell) set of sites. In sonicated total lipid extracts of red cell ghosts, phloretin binding consists of a single, saturable component. Its affinity and total number of sites are not significantly different from those of the low affinity binding process in ghosts. No high affinity binding of phloretin is exhibited by the red cell lipid extracts. Therefore, the high affinity phloretin binding sites are related to membrane proteins, and the low affinity sites result from phloretin binding to lipid. The identification of these two types of binding sites allows phloretin effects on protein-mediated transport processes to be distinguished from effects on the lipid region of the membrane.", "contents": "Interaction between phloretin and the red blood cell membrane. Phloretin binding to red blood cell components has been characterized at pH6, where binding and inhibitory potency are maximal. Binding to intact red cells and to purified hemoglobin are nonsaturated processes approximately equal in magnitude, which strongly suggests that most of the red cell binding may be ascribed to hemoglobin. This conclusion is supported by the fact that homoglobin-free red cell ghosts can bind only 10% as much phloretin as an equivalent number of red cells. The permeability of the red cell membrane to phloretin has been determined by a direct measurement at the time-course of the phloretin uptake. At a 2% hematocrit, the half time for phloretin uptake is 8.7s, corresponding to a permeability coefficient of 2 x 10(-4) cm/s. The concentration dependence of the binding to ghosts reveals two saturable components. Phloretin binds with high affinity (K diss = 1.5 muM) to about 2.5 x 10(6) sites per cell; it also binds with lower affinity (Kdiss = 54 muM) to a second (5.5 x 10(7) per cell) set of sites. In sonicated total lipid extracts of red cell ghosts, phloretin binding consists of a single, saturable component. Its affinity and total number of sites are not significantly different from those of the low affinity binding process in ghosts. No high affinity binding of phloretin is exhibited by the red cell lipid extracts. Therefore, the high affinity phloretin binding sites are related to membrane proteins, and the low affinity sites result from phloretin binding to lipid. The identification of these two types of binding sites allows phloretin effects on protein-mediated transport processes to be distinguished from effects on the lipid region of the membrane."}
{"id": "PMID:5576", "title": "Effect of synthetic substance P on monoaminergic mechanisms in brain.", "content": "Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia.", "contents": "Effect of synthetic substance P on monoaminergic mechanisms in brain. Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N'-(DL-SERYL)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine. Substance P appears to stimulate monoaminergic neurons in the brain and to serve as an excitatory transmitter in nerve terminals impinging upon dopaminergic cell bodies. A similar stimulation of noradrenaline and 5-hydroxytryptamine indicate a similar transmitter role for noradrenergic and serotonergic neurons. These data strengthen questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia."}
{"id": "PMID:5580", "title": "Gamma-glutamyl transpeptidase. Elevated activity in myotonic dystrophy.", "content": "gamma-Glutamyl transpeptidase, a membrane-bound enzyme playing an important role in the active amino acid transport across cellular membranes, is shown to be elevated in the serum of patients with myotonic muscular dystrophy. No increase of AP, LAP, GOT and GPT activities in the sera of some of the patients studied is observed. Possible interpretations in relation to the pathogenesis of myotonic dystrophy are discussed.", "contents": "Gamma-glutamyl transpeptidase. Elevated activity in myotonic dystrophy. gamma-Glutamyl transpeptidase, a membrane-bound enzyme playing an important role in the active amino acid transport across cellular membranes, is shown to be elevated in the serum of patients with myotonic muscular dystrophy. No increase of AP, LAP, GOT and GPT activities in the sera of some of the patients studied is observed. Possible interpretations in relation to the pathogenesis of myotonic dystrophy are discussed."}
{"id": "PMID:5581", "title": "Occurrence of a trypsin inhibitor in eggplant exocarps.", "content": "A trypsin inhibitor was extracted from eggplant exocarps with several buffers. The 0.1 M acetate buffer, pH 5.5. extract had the highest specific activity. The crude inhibitor, obtained by heat treatment and salting-out from the acetate buffer extract, contained 4.5% nitrogen and 22.6% hexose. Isoelectrofocusing demonstrated that this crude inhibitor in the eggplant exocarps was composed of at least three  forms, one of which differed in its isoelectric point. The form at pH 4.7 had the strongest activity. The molecular weights of these inhibitors were estimated to be between 5,000-10,000 by gel filtration.", "contents": "Occurrence of a trypsin inhibitor in eggplant exocarps. A trypsin inhibitor was extracted from eggplant exocarps with several buffers. The 0.1 M acetate buffer, pH 5.5. extract had the highest specific activity. The crude inhibitor, obtained by heat treatment and salting-out from the acetate buffer extract, contained 4.5% nitrogen and 22.6% hexose. Isoelectrofocusing demonstrated that this crude inhibitor in the eggplant exocarps was composed of at least three  forms, one of which differed in its isoelectric point. The form at pH 4.7 had the strongest activity. The molecular weights of these inhibitors were estimated to be between 5,000-10,000 by gel filtration."}
{"id": "PMID:5583", "title": "Ruptured coronary aneurysm and valvulitis in an infant with polyarteritis nodosa.", "content": "This report describes a 4-mth-old infant with polyarteritis nodosa who had a rapidly fatal course with the diagnosis ultimately being made at necropsy. The pathological lesions consisted of diffuse arterial disease with severe coronary involvement, and additional unusual features included a ruptured coronary artery aneurysm and a valvulitis of the mitral and aortic valves similar to that seen in rheumatic fever. The aetiology of polyarteritis is briefly summarised and the possibility of an immune reaction to foreign antigens, such as drugs or viruses, is considered.", "contents": "Ruptured coronary aneurysm and valvulitis in an infant with polyarteritis nodosa. This report describes a 4-mth-old infant with polyarteritis nodosa who had a rapidly fatal course with the diagnosis ultimately being made at necropsy. The pathological lesions consisted of diffuse arterial disease with severe coronary involvement, and additional unusual features included a ruptured coronary artery aneurysm and a valvulitis of the mitral and aortic valves similar to that seen in rheumatic fever. The aetiology of polyarteritis is briefly summarised and the possibility of an immune reaction to foreign antigens, such as drugs or viruses, is considered."}
{"id": "PMID:5584", "title": "Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents.", "content": "A three-year-old boy has coarse facial features, upper respiratory congestion, profound mental retardation, hepatosplenomegaly, increased height and head circumference, cataracts, a gibbus deformity, radiographic changes of dysostosis multiplex, and vacuolized peripheral lymphocytes. These findings are the most commonly reported clinical features in the previously described patients with mannosidosis. Our patient has a severe deficiency, and his parents have intermediate levels, of the acidic component of alpha-mannosidase in their cultured fibroblasts.", "contents": "Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents. A three-year-old boy has coarse facial features, upper respiratory congestion, profound mental retardation, hepatosplenomegaly, increased height and head circumference, cataracts, a gibbus deformity, radiographic changes of dysostosis multiplex, and vacuolized peripheral lymphocytes. These findings are the most commonly reported clinical features in the previously described patients with mannosidosis. Our patient has a severe deficiency, and his parents have intermediate levels, of the acidic component of alpha-mannosidase in their cultured fibroblasts."}
{"id": "PMID:5585", "title": "Maternal and fetal plasma levels of free corticosteroids in pathological deliveries.", "content": "Does intrauterine acidosis induce increased steroid secretion? The concentration of free steroids (CS) increases in both fetal and maternal plasma during labor and delivery. Fetal levels are higher after vaginal than after cesarean section. These differences may indicate an important role of the fetal adrenal gland in the induction of labor or they may reflect merely the fetal response to the stress of delivery. During incrased intrauterine stress steroid secretion is increased as shown here. We examined 41 mothers and their infants during pathological labor. Pathology was assessed from fetal acidosis and/or a clinically obstetric disease of the mother or fetus. The 41 cases included 9 cesarean sections, 8 forceps deliveries; 24 spontaneous deliveries of which 7 were premature. At the time of delivery the pH and CS level were determined in maternal and umbilical vessels in all cases. During spontaneous labor blood samples were also taken during the different stages of labour. A competetive protein binding assay with transcortin without fractionation of the steroids was used. Progesteron was determined by the same assay. The level of this hormone, however, remains unchanged and hence any changes reflect changes in CS. The levels of CS were correlated with the pH values and compared to previously obtained normal values. During pathological deliveries CS levels in both mother and fetus are normal as long as there is no acidosis (Fig. 1). If acidosis is present the CS level in the umbilical artery is usually higher than normal. In 13 out of 18 vaginal deliveries the CS level was above normal, in the other 5 at the upper limit of normal (Fig. 1 and 2). At the same time the a--v difference becomes smaller and sometimes even negative. No changes were noted in maternal and umbilical venous blood (Tab. I and II). Similar dependence on the pH was found for cesarean sections (Tab. III). In premature deliveries without acidosis in the umbilical artery the CS levels were lower in both mother and fetus (Tab. I). These results indicate that the fetal adrenal gland reacts to acidosis, i.e., intrauterine stress, with increased corticosteroid secretion. This rise depends on the pH of fetal blood and not on the type of delivery (Fig. 3).", "contents": "Maternal and fetal plasma levels of free corticosteroids in pathological deliveries. Does intrauterine acidosis induce increased steroid secretion? The concentration of free steroids (CS) increases in both fetal and maternal plasma during labor and delivery. Fetal levels are higher after vaginal than after cesarean section. These differences may indicate an important role of the fetal adrenal gland in the induction of labor or they may reflect merely the fetal response to the stress of delivery. During incrased intrauterine stress steroid secretion is increased as shown here. We examined 41 mothers and their infants during pathological labor. Pathology was assessed from fetal acidosis and/or a clinically obstetric disease of the mother or fetus. The 41 cases included 9 cesarean sections, 8 forceps deliveries; 24 spontaneous deliveries of which 7 were premature. At the time of delivery the pH and CS level were determined in maternal and umbilical vessels in all cases. During spontaneous labor blood samples were also taken during the different stages of labour. A competetive protein binding assay with transcortin without fractionation of the steroids was used. Progesteron was determined by the same assay. The level of this hormone, however, remains unchanged and hence any changes reflect changes in CS. The levels of CS were correlated with the pH values and compared to previously obtained normal values. During pathological deliveries CS levels in both mother and fetus are normal as long as there is no acidosis (Fig. 1). If acidosis is present the CS level in the umbilical artery is usually higher than normal. In 13 out of 18 vaginal deliveries the CS level was above normal, in the other 5 at the upper limit of normal (Fig. 1 and 2). At the same time the a--v difference becomes smaller and sometimes even negative. No changes were noted in maternal and umbilical venous blood (Tab. I and II). Similar dependence on the pH was found for cesarean sections (Tab. III). In premature deliveries without acidosis in the umbilical artery the CS levels were lower in both mother and fetus (Tab. I). These results indicate that the fetal adrenal gland reacts to acidosis, i.e., intrauterine stress, with increased corticosteroid secretion. This rise depends on the pH of fetal blood and not on the type of delivery (Fig. 3)."}
{"id": "PMID:5588", "title": "Gastric acid inactivation of erythromycin stearate in solid dosage forms.", "content": "The effect of hydrochloric acid at pH 1.2-3.2 ON ERYTHROMYCIN STEARATE AND COMMERCIAL DOSAGE FORMS OF ERYTHROMYCIN STEARATE WAS STUDIED. Under all conditions examined, erythromycin was readily dissolved from the stearate as hydrochloride, and rapidly lost its biological activity in solution. The inclusion of pepsin in the test systems did not affect the results. Although formulation differences somewhat affected the rate of destruction, acid lability was exhibited by all products examined, except enteric-coated tablets. Amounts of acid considered to be normal in the fasting stomach contents of adults during the time likely for a dose to remain in the stomach caused 70-90% destruction within 15 min after the shells started to rupture. Amounts of hydrochloric acid appreciably less than 1 mEq, representing abnormally small quantities even in the fasting state, caused destruction ranging from 30 to 70% of the doses in 15 min. These results are not reconcilable with published statements that the sensitivity of erythromycin to gastric acid is overcome by providing the antibiotic in the form of stearate salt.", "contents": "Gastric acid inactivation of erythromycin stearate in solid dosage forms. The effect of hydrochloric acid at pH 1.2-3.2 ON ERYTHROMYCIN STEARATE AND COMMERCIAL DOSAGE FORMS OF ERYTHROMYCIN STEARATE WAS STUDIED. Under all conditions examined, erythromycin was readily dissolved from the stearate as hydrochloride, and rapidly lost its biological activity in solution. The inclusion of pepsin in the test systems did not affect the results. Although formulation differences somewhat affected the rate of destruction, acid lability was exhibited by all products examined, except enteric-coated tablets. Amounts of acid considered to be normal in the fasting stomach contents of adults during the time likely for a dose to remain in the stomach caused 70-90% destruction within 15 min after the shells started to rupture. Amounts of hydrochloric acid appreciably less than 1 mEq, representing abnormally small quantities even in the fasting state, caused destruction ranging from 30 to 70% of the doses in 15 min. These results are not reconcilable with published statements that the sensitivity of erythromycin to gastric acid is overcome by providing the antibiotic in the form of stearate salt."}
{"id": "PMID:5589", "title": "Synthesis and alpha-adrenolytic activity of chiral beta-haloethylamines.", "content": "Several series of N,N-diaralkyl- and N-aryloxyalkyl-N-aralkyl-beta-haloethylamines were synthesized containing centers of chirality in the aralkyl substituent and in the beta-haloethyl moiety to study the stereoselectivity of alpha-adrenolytic activity of the beta-haloethylamines. These compounds were synthesized from starting materials of known absolute configuration via synthetic schemes that did not alter the stereochemical integrity of the chiral centers. Evaluation of the alpha-adrenolytic activities of these beta-haloethylamines on rat vas deferens indicated a variable degree of stereoselectivity of adrenergic blockade, which is interpreted in terms of drug-receptor interactions.", "contents": "Synthesis and alpha-adrenolytic activity of chiral beta-haloethylamines. Several series of N,N-diaralkyl- and N-aryloxyalkyl-N-aralkyl-beta-haloethylamines were synthesized containing centers of chirality in the aralkyl substituent and in the beta-haloethyl moiety to study the stereoselectivity of alpha-adrenolytic activity of the beta-haloethylamines. These compounds were synthesized from starting materials of known absolute configuration via synthetic schemes that did not alter the stereochemical integrity of the chiral centers. Evaluation of the alpha-adrenolytic activities of these beta-haloethylamines on rat vas deferens indicated a variable degree of stereoselectivity of adrenergic blockade, which is interpreted in terms of drug-receptor interactions."}
{"id": "PMID:5590", "title": "Rapid GLC determination of fusaric acid in biological fluids.", "content": "A simple, sensitive GLC assay was developed for fusaric acid, the active metabolite of bupicomide, to follow the disposition of this investigational antihypertensive agent in patients undergoing therapy. Fusaric acid is efficiently extracted from biological samples, derivatized by on-column methylation, and chromatographed using flame-ionization detection. An internal standard is utilized to quantitate results. The procedure is rapid and specific for fusaric acid, and has a lower limit of sensitivity of 0.1 mug/ml. The method is suitable for supporting pharmacokinetic studies of bupicomide following therapeutic doses in animals and humans.", "contents": "Rapid GLC determination of fusaric acid in biological fluids. A simple, sensitive GLC assay was developed for fusaric acid, the active metabolite of bupicomide, to follow the disposition of this investigational antihypertensive agent in patients undergoing therapy. Fusaric acid is efficiently extracted from biological samples, derivatized by on-column methylation, and chromatographed using flame-ionization detection. An internal standard is utilized to quantitate results. The procedure is rapid and specific for fusaric acid, and has a lower limit of sensitivity of 0.1 mug/ml. The method is suitable for supporting pharmacokinetic studies of bupicomide following therapeutic doses in animals and humans."}
{"id": "PMID:5591", "title": "Conformational populations for antihistamines and antihypertensives in solution.", "content": "The conformations in aqueous solution were determined for the XCH2CH2N systems of some antihistamines (H1-receptor antagonists) and some adrenergic neuron blocking agents, including the antihypertensive drugs guanethidine and guanoclor. The rotameric species thought to be the pharmacologically active one is often not the only rotamer present in solution.", "contents": "Conformational populations for antihistamines and antihypertensives in solution. The conformations in aqueous solution were determined for the XCH2CH2N systems of some antihistamines (H1-receptor antagonists) and some adrenergic neuron blocking agents, including the antihypertensive drugs guanethidine and guanoclor. The rotameric species thought to be the pharmacologically active one is often not the only rotamer present in solution."}
{"id": "PMID:5592", "title": "Determination of hyoscyamine in BPC mixtures.", "content": "The hyoscyamine contents of four BPC mixtures (containing either belladonna or hyoscyamus tincture) were determined using the acid-dye technique. A sample size of 10 ml was required. The mean percentage recovery of hyoscyamine ranged from 99.73 to 101.03 from three mixtures; from the magnesium trisilicate and belladonna mixture, it was 94.8. The effects of pH and adsorption on the extraction of the alkaloid-dye complex from the mixtures examined are discussed.", "contents": "Determination of hyoscyamine in BPC mixtures. The hyoscyamine contents of four BPC mixtures (containing either belladonna or hyoscyamus tincture) were determined using the acid-dye technique. A sample size of 10 ml was required. The mean percentage recovery of hyoscyamine ranged from 99.73 to 101.03 from three mixtures; from the magnesium trisilicate and belladonna mixture, it was 94.8. The effects of pH and adsorption on the extraction of the alkaloid-dye complex from the mixtures examined are discussed."}
{"id": "PMID:5594", "title": "Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions.", "content": "Microwave irradiation of 6 kw at 2450 MHz for 300 msec was sufficient to completely inactivate mouse brain cholinesterase and choline acetyltransferase. After this method of sacrifice, the acetylcholine contents of mouse brain regions, given in nanomoles per gram, were found to be: striatum, 81; medulla-pons, 44; diencephalon-midbrain, 34; hippocampus, 31; cerebral cortex, 26; and cerebellum, 17. Sodium pentobarbital caused a dose-dependent increase in whole brain acetylcholine. A maximal increase of 81% in whole brain was seen at 15 minutes with 80 mg/kg of sodium pentobarbital. The increase in acetylcholine after sodium pentobarbital treatment was not caused by anoxia from respiratory depression or by hypothermia. All brain regions except the cerebellum exhibited an increase in acetylcholine after pentobarbital treatment. Fifteen minutes after treatment, cerebellar acetylcholine was significantly decreased. However, at the time when half of the animals had regained the righting reflex, the unconscious mice showed an increase in cerebellar acetylcholine which was statistically significant  as compared to control. The relative accumulation rate of acetylcholine calculated for cerebral cortex and hippocampus was higher than that for striatum although the absolute rate of accumulation of ACh was higher in the striatum. Thus, after sodium pentobarbital treatment, the cerebral cortex and hippocampus exhibit a greater cholinergic response than the striatum.", "contents": "Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions. Microwave irradiation of 6 kw at 2450 MHz for 300 msec was sufficient to completely inactivate mouse brain cholinesterase and choline acetyltransferase. After this method of sacrifice, the acetylcholine contents of mouse brain regions, given in nanomoles per gram, were found to be: striatum, 81; medulla-pons, 44; diencephalon-midbrain, 34; hippocampus, 31; cerebral cortex, 26; and cerebellum, 17. Sodium pentobarbital caused a dose-dependent increase in whole brain acetylcholine. A maximal increase of 81% in whole brain was seen at 15 minutes with 80 mg/kg of sodium pentobarbital. The increase in acetylcholine after sodium pentobarbital treatment was not caused by anoxia from respiratory depression or by hypothermia. All brain regions except the cerebellum exhibited an increase in acetylcholine after pentobarbital treatment. Fifteen minutes after treatment, cerebellar acetylcholine was significantly decreased. However, at the time when half of the animals had regained the righting reflex, the unconscious mice showed an increase in cerebellar acetylcholine which was statistically significant  as compared to control. The relative accumulation rate of acetylcholine calculated for cerebral cortex and hippocampus was higher than that for striatum although the absolute rate of accumulation of ACh was higher in the striatum. Thus, after sodium pentobarbital treatment, the cerebral cortex and hippocampus exhibit a greater cholinergic response than the striatum."}
{"id": "PMID:5596", "title": "A test for antinociceptive activity of narcotic and narcotic antagonist analgesics in the guinea pig.", "content": "Ethylenediamine tetraacetic acid (EDTA) was used as a nociceptive stimulus intradermally in the guinea pig. The responses evoked by EDTA included vocalization, biting and scratching at the site of injection and escape behavior. Nociception by EDTA was shown to be the result of its cation chelating activity. The suppression of EDTA-induced responses proved to be a rapid and effective antinociceptive test. The narcotic analgesics morphine, codeine, meperidine and methadone and the narcotic antagonist analgesics cyclazocine, cyclorphan, nalorphine and pentazocine were active. The slopes of the dose-response curves of the narcotic antagonist analgesics were significantly shallower than those of the narcotic analgesics. The test was highly specific for these analgesics. Antipyretic analgesics and various nonanalgesic drugs were inactive.", "contents": "A test for antinociceptive activity of narcotic and narcotic antagonist analgesics in the guinea pig. Ethylenediamine tetraacetic acid (EDTA) was used as a nociceptive stimulus intradermally in the guinea pig. The responses evoked by EDTA included vocalization, biting and scratching at the site of injection and escape behavior. Nociception by EDTA was shown to be the result of its cation chelating activity. The suppression of EDTA-induced responses proved to be a rapid and effective antinociceptive test. The narcotic analgesics morphine, codeine, meperidine and methadone and the narcotic antagonist analgesics cyclazocine, cyclorphan, nalorphine and pentazocine were active. The slopes of the dose-response curves of the narcotic antagonist analgesics were significantly shallower than those of the narcotic analgesics. The test was highly specific for these analgesics. Antipyretic analgesics and various nonanalgesic drugs were inactive."}
{"id": "PMID:5597", "title": "Pharmacological characterization of adrenergic receptors of a rabbit cerebral artery in vitro.", "content": "In the light of controversy over the functional significance of the abundant sympathetic innervation of large cerebral blood vessels, an in vitro analysis of the adrenergic receptors mediating contractile effects in the rabbit basilar artery was undertaken. Beta adrenergic stimulation had no effect, and agents that block norepinephrine (NE) uptake did not alter contractile responses to l-NE. The l-NE dose-response curve could be resolved into two components S-shaped curves: the first had an ED50 OF 10(-5) M and reached a plateau at 10(-4) M; the second component continued above 10(-3) M without reaching a plateau. Phenylephrine and epinephrine dose-response curves were also biphasic; d-NE responses corresponded to the second phase of the l-NE curve. Relative potencies for the two components were different. For the first component, these were 1:0.23:0.18:0.03 for l-NE, epinephrine, phenylephrine and d-NE, respectively; relative potencies for the second component of the curve were 1:1:0.11:0.23. Phentolamine dissociation constants were analyzed separately for each component. The value for low l-NE concentrations was 5 X 10 (-8) M and, for higher concentrations, it was 3 X 10(-6) . The insensitivity of the alpha adrenergic receptor and the poor responsiveness of the muscle to its activation with agonist concentrations below 10(-4) M can probably account for the small contractile responses to nerve stimulation of large pial arteries in spite of their abundant innervation.", "contents": "Pharmacological characterization of adrenergic receptors of a rabbit cerebral artery in vitro. In the light of controversy over the functional significance of the abundant sympathetic innervation of large cerebral blood vessels, an in vitro analysis of the adrenergic receptors mediating contractile effects in the rabbit basilar artery was undertaken. Beta adrenergic stimulation had no effect, and agents that block norepinephrine (NE) uptake did not alter contractile responses to l-NE. The l-NE dose-response curve could be resolved into two components S-shaped curves: the first had an ED50 OF 10(-5) M and reached a plateau at 10(-4) M; the second component continued above 10(-3) M without reaching a plateau. Phenylephrine and epinephrine dose-response curves were also biphasic; d-NE responses corresponded to the second phase of the l-NE curve. Relative potencies for the two components were different. For the first component, these were 1:0.23:0.18:0.03 for l-NE, epinephrine, phenylephrine and d-NE, respectively; relative potencies for the second component of the curve were 1:1:0.11:0.23. Phentolamine dissociation constants were analyzed separately for each component. The value for low l-NE concentrations was 5 X 10 (-8) M and, for higher concentrations, it was 3 X 10(-6) . The insensitivity of the alpha adrenergic receptor and the poor responsiveness of the muscle to its activation with agonist concentrations below 10(-4) M can probably account for the small contractile responses to nerve stimulation of large pial arteries in spite of their abundant innervation."}
{"id": "PMID:5598", "title": "Cation-binding property of choroid plexus peptide IIF.", "content": "Preparations of the melanotropic-lipolytic peptide IIF from bovine choroid plexus contain 3% Ca, 1% Mg and less than 0.1% Na and K. Ca and Mg were removed by gel filtration on Sephadex G-10 in 1 N acetic acid. Capacity of the resulting cation-free peptide to bind Ca++, Mg++, Na+ and K+ was examined with the method of Hummel and Dreyer (Biochim. Biophys. Acta 63: 530-532, 1962). Peptide IIF bound a maximum of 3.7 to 4.4 mEq of Ca++, Mg++, Na+ or K+ per g of peptide. For each cation, linear Scatchard plot indicated one class of binding site. Association constants (liters per mole) were Ca++, 4.3 X 10(4); Mg++, 3.6 X 10(4); Na+, 4.8 X 10(2), K+, 1.9 X 10(2). Competitive binding experiments showed that all four cations occupied the same class of binding site.", "contents": "Cation-binding property of choroid plexus peptide IIF. Preparations of the melanotropic-lipolytic peptide IIF from bovine choroid plexus contain 3% Ca, 1% Mg and less than 0.1% Na and K. Ca and Mg were removed by gel filtration on Sephadex G-10 in 1 N acetic acid. Capacity of the resulting cation-free peptide to bind Ca++, Mg++, Na+ and K+ was examined with the method of Hummel and Dreyer (Biochim. Biophys. Acta 63: 530-532, 1962). Peptide IIF bound a maximum of 3.7 to 4.4 mEq of Ca++, Mg++, Na+ or K+ per g of peptide. For each cation, linear Scatchard plot indicated one class of binding site. Association constants (liters per mole) were Ca++, 4.3 X 10(4); Mg++, 3.6 X 10(4); Na+, 4.8 X 10(2), K+, 1.9 X 10(2). Competitive binding experiments showed that all four cations occupied the same class of binding site."}
{"id": "PMID:5599", "title": "A study of the mechanism of transport of diphenylhydantoin in the rat submaxillary gland in vitro.", "content": "In vitro studies performed on rat submaxillary gland slices with diphenylhydantoin (6 X 10(-6) M) showed that variations of extracellular pH (pHe) had no significant effects on uptake and only slight effects on efflux (lowering the pHe slightly decreased efflux rates, whereas increasing pHe slightly increased efflux rates). Increasing diphenylhydantoin concentration significantly decreased uptake and slightly increased the rate of efflux. Uptake of 14C-diphenylhydantoin was significantly decreased when compared to control conditions (pH 7.40, 37 degrees C, 100% O2 aeration, 6 X 10(-6) M) by the following alterations: aeration of the incubation medium with N2 instead of O2, decrease of bath temperature from 37 degrees C to 5 degrees C and addition of the following metabolic inhibitors: iodoacetic acid (10(-3)M), 2,4-dinitrophenol (10(-3)M) and cyanide (10(-3)M). Probenecid (10(-3)M) had no significant effect on diphenylhydantoin uptake when compared to control values. No evidence of salivary biotransformation of diphenylhydantoin was seen in the in vitro system using thin-layer chromatography. These in vitro data suggest an active transport process that is concentration-dependent with a possible saturable binding site on the membrane or in the interior of the cell.", "contents": "A study of the mechanism of transport of diphenylhydantoin in the rat submaxillary gland in vitro. In vitro studies performed on rat submaxillary gland slices with diphenylhydantoin (6 X 10(-6) M) showed that variations of extracellular pH (pHe) had no significant effects on uptake and only slight effects on efflux (lowering the pHe slightly decreased efflux rates, whereas increasing pHe slightly increased efflux rates). Increasing diphenylhydantoin concentration significantly decreased uptake and slightly increased the rate of efflux. Uptake of 14C-diphenylhydantoin was significantly decreased when compared to control conditions (pH 7.40, 37 degrees C, 100% O2 aeration, 6 X 10(-6) M) by the following alterations: aeration of the incubation medium with N2 instead of O2, decrease of bath temperature from 37 degrees C to 5 degrees C and addition of the following metabolic inhibitors: iodoacetic acid (10(-3)M), 2,4-dinitrophenol (10(-3)M) and cyanide (10(-3)M). Probenecid (10(-3)M) had no significant effect on diphenylhydantoin uptake when compared to control values. No evidence of salivary biotransformation of diphenylhydantoin was seen in the in vitro system using thin-layer chromatography. These in vitro data suggest an active transport process that is concentration-dependent with a possible saturable binding site on the membrane or in the interior of the cell."}
{"id": "PMID:5600", "title": "Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction.", "content": "The effects of the compounds 2-, 3- and 4-aminopyridine and sparteine on membrane conductance changes were examined using both voltage-clamped Myxicola axons and the lobster neuromuscular junction. In Myxicola axons, the aminopyridines very specifically inhibited the potassium conductance when applied at concentrations of 0.1 mM to 5 mM without any apparent effect of resting membrane potential. Concentrations in excess of 5 mM were needed to inhibit noticeably the sodium conductance. Potassium conductance-voltage curves were shifted in the depolarized direction along the voltage axis with no significant change in shape. There were only minor changes in the kinetics of potassium activation. In high potassium solutions, both inward and outward potassium currents were equally sensitive to the aminopyridines. Sparteine was, in general, found to be a more potent, but somewhat less specific, inhibitor of the potassium conductance. In contrast to the aminopyridines, sparteine was more effective when applied at basic pH and in addition tended to produce a noticeable degree of potassium inactivation. When applied to the lobster neuromuscular junction, 2-aminopyridine and sparteine dramatically increased the amplitude of both excitatory and inhibitory postjunctional potentials, with little or no change in resting potential, resting input conductance, reversal potential, or miniature end plate potential amplitude or frequency. Quantal content per fiber was increased by approximately a factor of 3 for the excitatory responses.", "contents": "Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction. The effects of the compounds 2-, 3- and 4-aminopyridine and sparteine on membrane conductance changes were examined using both voltage-clamped Myxicola axons and the lobster neuromuscular junction. In Myxicola axons, the aminopyridines very specifically inhibited the potassium conductance when applied at concentrations of 0.1 mM to 5 mM without any apparent effect of resting membrane potential. Concentrations in excess of 5 mM were needed to inhibit noticeably the sodium conductance. Potassium conductance-voltage curves were shifted in the depolarized direction along the voltage axis with no significant change in shape. There were only minor changes in the kinetics of potassium activation. In high potassium solutions, both inward and outward potassium currents were equally sensitive to the aminopyridines. Sparteine was, in general, found to be a more potent, but somewhat less specific, inhibitor of the potassium conductance. In contrast to the aminopyridines, sparteine was more effective when applied at basic pH and in addition tended to produce a noticeable degree of potassium inactivation. When applied to the lobster neuromuscular junction, 2-aminopyridine and sparteine dramatically increased the amplitude of both excitatory and inhibitory postjunctional potentials, with little or no change in resting potential, resting input conductance, reversal potential, or miniature end plate potential amplitude or frequency. Quantal content per fiber was increased by approximately a factor of 3 for the excitatory responses."}
{"id": "PMID:5601", "title": "Effects of calcium on the local anesthetic suppression of ionic conductances in squid axon membranes.", "content": "The effects of varying the external calcium concentration on the suppression of membrane ionic conductances by procaine and benzocaine have been examined under voltage-clamped conditions. The suppression of peak conductance and steady-state conductance by procaine or benzocaine applied externally or internally was not affected by changing the external calcium concentration between 10 and 100 mM. When the calcium concentration was lowered below 10 mM (5 or 2 mM), the procaine effect was slightly potentiated. This augmentation could not be ascribed to an acceleration in the rate of penetration of procaine into the axon in low calcium solutions. The resting membrane conductance was slightly decreased by procaine in a manner independent of the external calcium concentration. The maximum effect of procaine on resting conductances was obtained at a concentration much lower than that required for maximum suppression of peak and steady-state conductances. The present results are not compatible with the hypothesis that calcium competes with local anesthetics for a negatively charged site on the membrane. It is suggested that hydrophobic interactions of local anesthetic molecules with the membrane affect the resting membrane conductance whereas coulombic interactions are responsible for the conductance changes observed during nerve activity.", "contents": "Effects of calcium on the local anesthetic suppression of ionic conductances in squid axon membranes. The effects of varying the external calcium concentration on the suppression of membrane ionic conductances by procaine and benzocaine have been examined under voltage-clamped conditions. The suppression of peak conductance and steady-state conductance by procaine or benzocaine applied externally or internally was not affected by changing the external calcium concentration between 10 and 100 mM. When the calcium concentration was lowered below 10 mM (5 or 2 mM), the procaine effect was slightly potentiated. This augmentation could not be ascribed to an acceleration in the rate of penetration of procaine into the axon in low calcium solutions. The resting membrane conductance was slightly decreased by procaine in a manner independent of the external calcium concentration. The maximum effect of procaine on resting conductances was obtained at a concentration much lower than that required for maximum suppression of peak and steady-state conductances. The present results are not compatible with the hypothesis that calcium competes with local anesthetics for a negatively charged site on the membrane. It is suggested that hydrophobic interactions of local anesthetic molecules with the membrane affect the resting membrane conductance whereas coulombic interactions are responsible for the conductance changes observed during nerve activity."}
{"id": "PMID:5602", "title": "Twitch potentiation of skeletal muscle by physostigmine at different pH.", "content": "This report extends earlier research, done with external media at pH 7.2, to new studies at pH 6.4 and 8.4 as well as 7.2, to determine the roles of the protonated and neutral forms of physostigmine (a weak base with pKalpha = 8.2) in causing twitch potentiation of the frog sartorius muscle. Physostigmine, especially at relatively high pH (8.4) and concentration (1.5 mM), considerably blocks excitation. However, the results show in general that physostigmine potentiation increased peak contraction time and thereby indicate that potentiation is occurring in terms of prolongation of the active state. At pH 6.4 and 8.4, 1 mM physostigmine causes no change in the mechanical threshold of K depolarization contractures of toe muscles, as found previously at pH 7.2. Physostigmine increasingly prolongs the action potential as pH rises, i.e., in positive correlation with the twitch potentiation, thus indicating that this electrical change is the prime determinant of the potentiation.", "contents": "Twitch potentiation of skeletal muscle by physostigmine at different pH. This report extends earlier research, done with external media at pH 7.2, to new studies at pH 6.4 and 8.4 as well as 7.2, to determine the roles of the protonated and neutral forms of physostigmine (a weak base with pKalpha = 8.2) in causing twitch potentiation of the frog sartorius muscle. Physostigmine, especially at relatively high pH (8.4) and concentration (1.5 mM), considerably blocks excitation. However, the results show in general that physostigmine potentiation increased peak contraction time and thereby indicate that potentiation is occurring in terms of prolongation of the active state. At pH 6.4 and 8.4, 1 mM physostigmine causes no change in the mechanical threshold of K depolarization contractures of toe muscles, as found previously at pH 7.2. Physostigmine increasingly prolongs the action potential as pH rises, i.e., in positive correlation with the twitch potentiation, thus indicating that this electrical change is the prime determinant of the potentiation."}
{"id": "PMID:5603", "title": "The renal blood flow and the glomerular filtration rate of anaesthetized dogs during acute changes in plasma sodium concentration.", "content": "1. The effects of acute changes in plasma Na concentration (P(Na)) on renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in anaesthetized greyhounds. Saline was infused at a constant rate (0.1 ml. kg(-1) min(-1)) either into a renal artery or into a systemic vein. Plasma Na concentration was altered by varying the Na concentration of the infused saline from 0.154 to 0.077, 0.616 or 1.232 M.2. Blood pressure (B.P.), packed cell volume (PCV), concentration of plasma solids (PS) and the plasma concentration of H(+) and K (P(K)) ions were measured but no attempt was made to contain their fluctuation.3. An infusion of hypertonic saline into a renal artery usually led to an ipsilateral increase in RBF for 5-15 min, followed by a progressive fall. Over-all, mean values of RBF fell with P(Na) throughout the range studied (120-190 m-mole l.(-1)). Glomerular filtration rate rose with P(Na) to reach maximal values at P(Na) levels of 140-160 m-mole l.(-1), but fell thereafter. The combined fall in RBF and GFR, without change in filtration fraction, at P(Na) values above 160 m-mole l.(-1) is consistent with an alteration in afferent arteriolar resistance. The fall in GFR despite a rise in RBF noted when P(Na) was reduced below 140 m-mole l.(-1) requires an additional explanation.4. Renal blood flow was independent of P(K); it was inversely related to [H(+)] and directly related to PS. Glomerular filtration rate was independent of PCV and P(K). It was also inversely related to [H(+)] and directly related to PS up to a value of 6 g 100 g(-1) plasma, after which the relationship was reversed. These results suggest that the renal vascular responses to acute changes in P(Na) may be mediated in part, at least, by concurrent change in PS and [H(+)].", "contents": "The renal blood flow and the glomerular filtration rate of anaesthetized dogs during acute changes in plasma sodium concentration. 1. The effects of acute changes in plasma Na concentration (P(Na)) on renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in anaesthetized greyhounds. Saline was infused at a constant rate (0.1 ml. kg(-1) min(-1)) either into a renal artery or into a systemic vein. Plasma Na concentration was altered by varying the Na concentration of the infused saline from 0.154 to 0.077, 0.616 or 1.232 M.2. Blood pressure (B.P.), packed cell volume (PCV), concentration of plasma solids (PS) and the plasma concentration of H(+) and K (P(K)) ions were measured but no attempt was made to contain their fluctuation.3. An infusion of hypertonic saline into a renal artery usually led to an ipsilateral increase in RBF for 5-15 min, followed by a progressive fall. Over-all, mean values of RBF fell with P(Na) throughout the range studied (120-190 m-mole l.(-1)). Glomerular filtration rate rose with P(Na) to reach maximal values at P(Na) levels of 140-160 m-mole l.(-1), but fell thereafter. The combined fall in RBF and GFR, without change in filtration fraction, at P(Na) values above 160 m-mole l.(-1) is consistent with an alteration in afferent arteriolar resistance. The fall in GFR despite a rise in RBF noted when P(Na) was reduced below 140 m-mole l.(-1) requires an additional explanation.4. Renal blood flow was independent of P(K); it was inversely related to [H(+)] and directly related to PS. Glomerular filtration rate was independent of PCV and P(K). It was also inversely related to [H(+)] and directly related to PS up to a value of 6 g 100 g(-1) plasma, after which the relationship was reversed. These results suggest that the renal vascular responses to acute changes in P(Na) may be mediated in part, at least, by concurrent change in PS and [H(+)]."}
{"id": "PMID:5604", "title": "Hydrolytic enzymes of Euglena gracilis: characterization and activity as a function of culture age and carbon deprivation.", "content": "Optimal assay conditions are described for 8 hydrolases of Euglena gracilis var. bacillaris, SM-L1 (streptomycin-bleached) strain, 7 of which have an acid pH-optimum. Acid-phosphatase, beta-galactosidase, beta-glucosidase, b-fucosidase, cathepsin D, RNase, DNase, and an esterase are active in cell homogenates. Amylase has very low activity, and beta-glucuronidase, arylsulfatase, beta, N-acetyl-glucosaminidase, alpha-fucosidase, and alpha- and beta-mannosidase are inactive.", "contents": "Hydrolytic enzymes of Euglena gracilis: characterization and activity as a function of culture age and carbon deprivation. Optimal assay conditions are described for 8 hydrolases of Euglena gracilis var. bacillaris, SM-L1 (streptomycin-bleached) strain, 7 of which have an acid pH-optimum. Acid-phosphatase, beta-galactosidase, beta-glucosidase, b-fucosidase, cathepsin D, RNase, DNase, and an esterase are active in cell homogenates. Amylase has very low activity, and beta-glucuronidase, arylsulfatase, beta, N-acetyl-glucosaminidase, alpha-fucosidase, and alpha- and beta-mannosidase are inactive."}
{"id": "PMID:5607", "title": "Adrenergic sulfonanilides. 4. Centrally active beta-adrenergic agonists.", "content": "The central nervous system (CNS) activities of a number of soterenol analogs have been investigated, and several of these compounds possessed potent morphine antagonistic and anorexiant properties. The CNS activity of these compounds was enhanced by certain lipophilic [e.g., 1,1-dimethyl-2-phenethyl (43) or cyclopropyl (40 and 44)] nitrogen substituents; however, minor structural changes on either the aromatic or side-chain moieties drastically reduced central activity. Toxicity in this series was related to the inherent alpha-adrenergic stimulating component (direct or indirect).", "contents": "Adrenergic sulfonanilides. 4. Centrally active beta-adrenergic agonists. The central nervous system (CNS) activities of a number of soterenol analogs have been investigated, and several of these compounds possessed potent morphine antagonistic and anorexiant properties. The CNS activity of these compounds was enhanced by certain lipophilic [e.g., 1,1-dimethyl-2-phenethyl (43) or cyclopropyl (40 and 44)] nitrogen substituents; however, minor structural changes on either the aromatic or side-chain moieties drastically reduced central activity. Toxicity in this series was related to the inherent alpha-adrenergic stimulating component (direct or indirect)."}
{"id": "PMID:5611", "title": "Ontogenetic development of NADH-dependent methemoglobin reductase in erythrocytes of man and rat.", "content": "Ontogenetic development of NADH-dependent methemoglobin reductase was followed in humans and rats. The human kinetic profile differs from that in the rat. The low level of methemoglobin reductase in human infants at birth and for the first months of life may provide a partial explanation of the particular susceptibility to methemoglobinemic agents of this age group.", "contents": "Ontogenetic development of NADH-dependent methemoglobin reductase in erythrocytes of man and rat. Ontogenetic development of NADH-dependent methemoglobin reductase was followed in humans and rats. The human kinetic profile differs from that in the rat. The low level of methemoglobin reductase in human infants at birth and for the first months of life may provide a partial explanation of the particular susceptibility to methemoglobinemic agents of this age group."}
{"id": "PMID:5612", "title": "Biotransformation, sex hormones, and toxicity of two volatile anesthetics in mice.", "content": "Male and female DBA 11 mice recovered from 1 hr of anesthesia with chloroform of fluoroxene apparently unharmed. However, many of the animals died within 24-48 hr after anesthesia. Pretreatment with phenobarbital increased, while pretreatment with a small dose of carbon tetrachloride decreased, this toxicity. Relatively more males than females died. Pretreatment with estradiol in males and testosterone in females reversed this ratio. We conclude that the murine toxicity of chloroform and fluoxene is dependent on biotransformation by hepatic microsomal enzymes and that the testosterone enhances postanesthetic toxicity of these agents.", "contents": "Biotransformation, sex hormones, and toxicity of two volatile anesthetics in mice. Male and female DBA 11 mice recovered from 1 hr of anesthesia with chloroform of fluoroxene apparently unharmed. However, many of the animals died within 24-48 hr after anesthesia. Pretreatment with phenobarbital increased, while pretreatment with a small dose of carbon tetrachloride decreased, this toxicity. Relatively more males than females died. Pretreatment with estradiol in males and testosterone in females reversed this ratio. We conclude that the murine toxicity of chloroform and fluoxene is dependent on biotransformation by hepatic microsomal enzymes and that the testosterone enhances postanesthetic toxicity of these agents."}
{"id": "PMID:5613", "title": "Neuronal control of neurotransmitters biosynthesis during development.", "content": "Studies on neuronal control mechanisms of neurotransmitters biosynthesis during the development of peripheral and central autonomic synapses are reviewed. Particular emphasis is placed on investigations of developing peripheral sympathetic ganglia and brain in chick embryo and chick. Studies on the development of autonomic neurons and synapses under different pharmacological conditions are reported. Principally the effect of a) the administration of drugs and precursors such as L-dopa, 3H-dopa, 6-OH dopa; b) the prenatal administration of reserpine; c) the blockade of cholinergic receptors; d) the nerve growth factor (NGF) is analyzed. Results of developmental studies on chick ciliary ganglia are summarized. The review particulary underlines the importance of combining the use of sensitive microchemical methods to pharmacological tools in exploring the development of regulatory mechanisms at the cellular level.", "contents": "Neuronal control of neurotransmitters biosynthesis during development. Studies on neuronal control mechanisms of neurotransmitters biosynthesis during the development of peripheral and central autonomic synapses are reviewed. Particular emphasis is placed on investigations of developing peripheral sympathetic ganglia and brain in chick embryo and chick. Studies on the development of autonomic neurons and synapses under different pharmacological conditions are reported. Principally the effect of a) the administration of drugs and precursors such as L-dopa, 3H-dopa, 6-OH dopa; b) the prenatal administration of reserpine; c) the blockade of cholinergic receptors; d) the nerve growth factor (NGF) is analyzed. Results of developmental studies on chick ciliary ganglia are summarized. The review particulary underlines the importance of combining the use of sensitive microchemical methods to pharmacological tools in exploring the development of regulatory mechanisms at the cellular level."}
{"id": "PMID:5614", "title": "Isolation and properties of the replicase of encephalomyocarditis virus.", "content": "The RNA-dependent RNA polymerase (replicase) of encephalomyocarditis (EMC) virus was found to be closely associated with the smooth membranes of infected BHK-21 cells. An RNA-dependent EMC replicase was extracted from the membranes with 0.15% sodium dodecyl sulfate (SDS) and 1,1,2-trichlorotri-fluoroethane (Genetron 113) and further purified by high-salt dextran-polyethylene glycol phase separation, sievorptive chromatography, and glycerol gradient sedimentation. The enzyme does not manifest strict specificity toward EMC RNA template. It can use also Qbeta RNA, rRNA of BHK cells, or poly(C). SDS-polyacrylamide gel electrophoresis of purified EMC replicase labeled with radioactive methionine revealed that, of all the stable EMC proteins, the enzyme contains predominantly the 56,000-dalton (E) polypeptide.", "contents": "Isolation and properties of the replicase of encephalomyocarditis virus. The RNA-dependent RNA polymerase (replicase) of encephalomyocarditis (EMC) virus was found to be closely associated with the smooth membranes of infected BHK-21 cells. An RNA-dependent EMC replicase was extracted from the membranes with 0.15% sodium dodecyl sulfate (SDS) and 1,1,2-trichlorotri-fluoroethane (Genetron 113) and further purified by high-salt dextran-polyethylene glycol phase separation, sievorptive chromatography, and glycerol gradient sedimentation. The enzyme does not manifest strict specificity toward EMC RNA template. It can use also Qbeta RNA, rRNA of BHK cells, or poly(C). SDS-polyacrylamide gel electrophoresis of purified EMC replicase labeled with radioactive methionine revealed that, of all the stable EMC proteins, the enzyme contains predominantly the 56,000-dalton (E) polypeptide."}
{"id": "PMID:5615", "title": "Comparative properties of bacteriophage phi6 and phi6 nucleocapsid.", "content": "Nonionic detergent treatments released a nucleocapsid from the enveloped bacteriphage phi6. The nucleocapsid sedimented at nearly the same rate as the whole phage in sucrose density gradients, but the buoyant density in Cs2S04 changed from 1.22 g/cm3 for the whole phage to 1.33 g/cm3 for the nucleocapsid. The detergent completely removed the lipid and 5 of the 10 proteins from the phage. Surface labeling of the phage and nucleocapsid with 125I revealed that protein P3 was on the outer surface of the whole phage and P8 was on the surface of the nucleocapsid. Both the phage and the nucleocapsid were stable between pH 6.0 and 9.5. Low concentrations of EDTA (10-4 M) dissociated the nucleocapsid but had no effect on the whole phage. The nucleocapsid contained all three double-stranded RNA segments, as well as RNA polymerase activity.", "contents": "Comparative properties of bacteriophage phi6 and phi6 nucleocapsid. Nonionic detergent treatments released a nucleocapsid from the enveloped bacteriphage phi6. The nucleocapsid sedimented at nearly the same rate as the whole phage in sucrose density gradients, but the buoyant density in Cs2S04 changed from 1.22 g/cm3 for the whole phage to 1.33 g/cm3 for the nucleocapsid. The detergent completely removed the lipid and 5 of the 10 proteins from the phage. Surface labeling of the phage and nucleocapsid with 125I revealed that protein P3 was on the outer surface of the whole phage and P8 was on the surface of the nucleocapsid. Both the phage and the nucleocapsid were stable between pH 6.0 and 9.5. Low concentrations of EDTA (10-4 M) dissociated the nucleocapsid but had no effect on the whole phage. The nucleocapsid contained all three double-stranded RNA segments, as well as RNA polymerase activity."}
{"id": "PMID:5616", "title": "Urologic manifestations of polyarteritis nodosa.", "content": "Polyarteritis nodosa is an unusual condition that infrequently presents with signs and symptoms essentially confined to the urinary system. Such a case necessitating bilateral nephrectomy owing to hemorrhage is described. The pathologic findings, pathophysiology and etiology of the condition as well as treatment by renal transplatation are discussed.", "contents": "Urologic manifestations of polyarteritis nodosa. Polyarteritis nodosa is an unusual condition that infrequently presents with signs and symptoms essentially confined to the urinary system. Such a case necessitating bilateral nephrectomy owing to hemorrhage is described. The pathologic findings, pathophysiology and etiology of the condition as well as treatment by renal transplatation are discussed."}
{"id": "PMID:5617", "title": "[Effects of pH on the processes of excitation-contraction coupling of bullfrog atrium (author's transl)].", "content": "It has long been demonstrated that in cardiac muscle alterations in the extracellular pH exhibit a remarkable inotropic effect, whereas the precise mechanism is not fully clarified yet in spite of many associated thories. In recent years, however, abundant informations about the processes of excitation-contraction coupling (E-C coupling) of cardiac muscle have been obtained. Accordingly, the mechanisms of inotropic actions of pH on cardiac muscles must also be re-examined on the basis of these lately developed theories of E-C coupling. In the present experiment, therefore, we attempted to elucidate the fundamental mechanism of actions of pH upon several processes of E-C coupling using the bullfrog atrium whose processes of E-C coupling have been fairly well known...", "contents": "[Effects of pH on the processes of excitation-contraction coupling of bullfrog atrium (author's transl)]. It has long been demonstrated that in cardiac muscle alterations in the extracellular pH exhibit a remarkable inotropic effect, whereas the precise mechanism is not fully clarified yet in spite of many associated thories. In recent years, however, abundant informations about the processes of excitation-contraction coupling (E-C coupling) of cardiac muscle have been obtained. Accordingly, the mechanisms of inotropic actions of pH on cardiac muscles must also be re-examined on the basis of these lately developed theories of E-C coupling. In the present experiment, therefore, we attempted to elucidate the fundamental mechanism of actions of pH upon several processes of E-C coupling using the bullfrog atrium whose processes of E-C coupling have been fairly well known..."}
{"id": "PMID:5619", "title": "[Gentamicin-susceptibility of various pathogens isolated from clinical materials].", "content": "We studied on the antibacterial activity of gentamicin against various pathogens isolated from clinical materials mainly isolated during 1974 and 1975, comparing with other antibiotics. Beta hemolytic streptococci, pneumococci and enterococci are less susceptible to gentamicin than staphylococci. Staph, aureus and Staph. epidermidis resistant to various antibiotics are very susceptible to gentamicin, and no resistant strain to this drug was found. Haemophilus influenzae, H. parainfluenzae and H. parahaemolyticus are very susceptible to gentamicin, and there is no resistant strain to this drug. Escherichia coli, Klebsiella, Citrobacter, Serratia and five species of Proteus are more susceptible to gentamicin and tobramycin than dibekacin and amikacin. A few resistant or less susceptible strains to gentamicin are found in E. coli, Citrobacerr, Serratia, Pr. morganii and Pr. rettgeri. Pr. inconstans is less susceptible to gentamicin than other species of Proteus. Antibacterial activity of gentamicin against Pseudomonas aeruginosa is very strong, but dibekacin and tobramycin are stronger. Gentamicin-resistant strains of Pseudomonas aeruginosa are now rather few.", "contents": "[Gentamicin-susceptibility of various pathogens isolated from clinical materials]. We studied on the antibacterial activity of gentamicin against various pathogens isolated from clinical materials mainly isolated during 1974 and 1975, comparing with other antibiotics. Beta hemolytic streptococci, pneumococci and enterococci are less susceptible to gentamicin than staphylococci. Staph, aureus and Staph. epidermidis resistant to various antibiotics are very susceptible to gentamicin, and no resistant strain to this drug was found. Haemophilus influenzae, H. parainfluenzae and H. parahaemolyticus are very susceptible to gentamicin, and there is no resistant strain to this drug. Escherichia coli, Klebsiella, Citrobacter, Serratia and five species of Proteus are more susceptible to gentamicin and tobramycin than dibekacin and amikacin. A few resistant or less susceptible strains to gentamicin are found in E. coli, Citrobacerr, Serratia, Pr. morganii and Pr. rettgeri. Pr. inconstans is less susceptible to gentamicin than other species of Proteus. Antibacterial activity of gentamicin against Pseudomonas aeruginosa is very strong, but dibekacin and tobramycin are stronger. Gentamicin-resistant strains of Pseudomonas aeruginosa are now rather few."}
{"id": "PMID:5621", "title": "Effects of changing levels of glucocorticosteroids on heat exposure in rabbit.", "content": "Rabbits exposed for one hour to a temperature of 40degrees Cand 35-37% humidity showed elevated plasma osmolality and pH. Most of the animals were not able to withstand the heat. Dexamethasone-treated rabbits under the same conditions withstood the heat better and their plasma pH and osmolality remained constant. Metopirone-treated rabbits withstood the heat and showed a rise in plasma osmolality and a slight change in plasma pH. The highest rise in rectal temperature was observed in the metopirone-treated rabbits. Only the untreated animals were unable to regain pre-exposure rectal temperature. The results suggest that high levels of glucocorticosteroids enhance neurogenic and metabolic mechanisms which have protective functions during acute exposure to heat.", "contents": "Effects of changing levels of glucocorticosteroids on heat exposure in rabbit. Rabbits exposed for one hour to a temperature of 40degrees Cand 35-37% humidity showed elevated plasma osmolality and pH. Most of the animals were not able to withstand the heat. Dexamethasone-treated rabbits under the same conditions withstood the heat better and their plasma pH and osmolality remained constant. Metopirone-treated rabbits withstood the heat and showed a rise in plasma osmolality and a slight change in plasma pH. The highest rise in rectal temperature was observed in the metopirone-treated rabbits. Only the untreated animals were unable to regain pre-exposure rectal temperature. The results suggest that high levels of glucocorticosteroids enhance neurogenic and metabolic mechanisms which have protective functions during acute exposure to heat."}
{"id": "PMID:5622", "title": "Changes in contractility and calcium binding of guinea pig taenia coli by treatment with enzymes which hydrolyze sialic acid.", "content": "The effects of neuraminidase and phospholipase C on the contractility and the Ca++ -binding of guinea pig taenia coli were investigated. Potassium contracture or histamine-induced contracture of taenia coli was inhibited by treatment with neuraminidase, though acetylcholine-induced contracture was not. Treatment with phospholipase C markedly inhibited the contracture induced by isotonic potassium, histamine or acetylcholine. By treatment with neuraminidase for 4 hr, about 40 mumol/100 mg wer wt of sialic acid was released from taenia coli. This corresponded to two-fifths of total content of sialic acid. By treatment with phospholipase C for 2 hr, a similar amount of sialic acid to that produced  by neuraminidase treatment was released. The Scarchard plot of Ca++-binding was a biphasic pattern indicating the presence of two types ofthe Ca++ -binding site with different affinity constants. Neuraminidase produced a 57% decrease in the amount of bound Ca++. The Scatchard plot of Ca++ -binding changed to a monophasic pattern indicating the disapperance of thel ow affinity Ca++ -binding site. Phospholipase C caused a 59% decrease of bound Ca++. The Scatchard plot also indicated the disappearance of the low affinity Ca++ -binding site. From these results, we speculated that sialicacid residue of surface membrane of the muscle cell was first site in the Ca++ -influx mechanism.", "contents": "Changes in contractility and calcium binding of guinea pig taenia coli by treatment with enzymes which hydrolyze sialic acid. The effects of neuraminidase and phospholipase C on the contractility and the Ca++ -binding of guinea pig taenia coli were investigated. Potassium contracture or histamine-induced contracture of taenia coli was inhibited by treatment with neuraminidase, though acetylcholine-induced contracture was not. Treatment with phospholipase C markedly inhibited the contracture induced by isotonic potassium, histamine or acetylcholine. By treatment with neuraminidase for 4 hr, about 40 mumol/100 mg wer wt of sialic acid was released from taenia coli. This corresponded to two-fifths of total content of sialic acid. By treatment with phospholipase C for 2 hr, a similar amount of sialic acid to that produced  by neuraminidase treatment was released. The Scarchard plot of Ca++-binding was a biphasic pattern indicating the presence of two types ofthe Ca++ -binding site with different affinity constants. Neuraminidase produced a 57% decrease in the amount of bound Ca++. The Scatchard plot of Ca++ -binding changed to a monophasic pattern indicating the disapperance of thel ow affinity Ca++ -binding site. Phospholipase C caused a 59% decrease of bound Ca++. The Scatchard plot also indicated the disappearance of the low affinity Ca++ -binding site. From these results, we speculated that sialicacid residue of surface membrane of the muscle cell was first site in the Ca++ -influx mechanism."}
{"id": "PMID:5623", "title": "[Treatment of acute respiratory insufficiency in cardiac surgery].", "content": "An analysis of the main causes of acute respiratory insufficiency as a frequently observed and severe complication of the early postoperative period after open-heart surgery is presented. To permit differentiated employment of respiratory resuscitation measures, subcompensated and decompensated forms of acute postoperative respiratory insufficiency were distinguished on the basis of clinical and laboratory data. The most efficient methods of treatment of this complication are described, including the employment of helium, ultrasonic inhalator, therapeutic intubation, bronchoscopy, long-term automated artificial pulmonary ventilation. A combined employment of the modified methods of respiratory resuscitation permitted to improve the course of acute respiratory insufficiency and to reduce the mortality nearly three-fold.", "contents": "[Treatment of acute respiratory insufficiency in cardiac surgery]. An analysis of the main causes of acute respiratory insufficiency as a frequently observed and severe complication of the early postoperative period after open-heart surgery is presented. To permit differentiated employment of respiratory resuscitation measures, subcompensated and decompensated forms of acute postoperative respiratory insufficiency were distinguished on the basis of clinical and laboratory data. The most efficient methods of treatment of this complication are described, including the employment of helium, ultrasonic inhalator, therapeutic intubation, bronchoscopy, long-term automated artificial pulmonary ventilation. A combined employment of the modified methods of respiratory resuscitation permitted to improve the course of acute respiratory insufficiency and to reduce the mortality nearly three-fold."}
{"id": "PMID:5625", "title": "[Isoenzyme differentiation of gamma-glutamyltransferase by concanavalin A and Con- A-Sepharose (author's transl)].", "content": "In this investigation a new possibility of isoenzyme-differentiation of the gamma-glutamyl-transferase (GGT) (EC Nr.2.3.2.2.) was demonstrated by Concanavalin A and Con A-Sepharose. Because of the different sugar content of the glycoproteins distinction between liver- and kidney-GGT is possible. Furthermore it was possible for the first time to show a different precipitation behaviour of one glycoprotein to Concanavalin A in certain diseases. In cases of alcoholic hepatitis GGT looses its Concanavalin A-affinity because of increased neuraminic acid concentration. The possible reasons of the different behaviour to the binding affinity of Con A and Con A-Sepharose and GGT as well as additional use for enzyme-differentiation by Con A-Sepharose affinity chromatography are discussed.", "contents": "[Isoenzyme differentiation of gamma-glutamyltransferase by concanavalin A and Con- A-Sepharose (author's transl)]. In this investigation a new possibility of isoenzyme-differentiation of the gamma-glutamyl-transferase (GGT) (EC Nr.2.3.2.2.) was demonstrated by Concanavalin A and Con A-Sepharose. Because of the different sugar content of the glycoproteins distinction between liver- and kidney-GGT is possible. Furthermore it was possible for the first time to show a different precipitation behaviour of one glycoprotein to Concanavalin A in certain diseases. In cases of alcoholic hepatitis GGT looses its Concanavalin A-affinity because of increased neuraminic acid concentration. The possible reasons of the different behaviour to the binding affinity of Con A and Con A-Sepharose and GGT as well as additional use for enzyme-differentiation by Con A-Sepharose affinity chromatography are discussed."}
{"id": "PMID:5626", "title": "Investigations on the function of the rat forestomach.", "content": "The functions of the rat forestomach and upper digestive tract were studied. The pH values, alpha-amylase activity, quantitative estimates of microorganisms, and emptying rates were higher in the forestomach than in the glandular stomach. Rats with surgically removed forestomachs lived without complications for more than 1 yr. Their alimentary hyperglycemia was higher and shorter than in controls. The significance of rich microflora present in the conventional forestomach is not known, although in this function between man and ruminants were discussed.", "contents": "Investigations on the function of the rat forestomach. The functions of the rat forestomach and upper digestive tract were studied. The pH values, alpha-amylase activity, quantitative estimates of microorganisms, and emptying rates were higher in the forestomach than in the glandular stomach. Rats with surgically removed forestomachs lived without complications for more than 1 yr. Their alimentary hyperglycemia was higher and shorter than in controls. The significance of rich microflora present in the conventional forestomach is not known, although in this function between man and ruminants were discussed."}
{"id": "PMID:5627", "title": "Removal of basement membrane in the involuting breast.", "content": "Morphologic and immunohistochemical studies by light and electron microscopy indicated that basement membrane was removed during the process of involution of the murine breast. Removal of the basement membrane started 2 days postweaning, was maximal at 4 days, and correlated with degeneration of epithelial cells. There was no evidence of phagocytosis of basement membrane, so the removal of this antigen was attributed to enzymatic hydrolysis. To determine the activity of breast homogenate on the specific basement membrane antigen, insoluble basement membrane embedded in agarose gels was incubated with breast liver and kidney homogenates. When basement membrane antigen was demonstrated by the specific antibody, it was found that breast homogenate solubilized basement membrane but liver and kidney failed to solubilize basement membrane. To quantify the reaction and determine some of the characteristics of the responsible enzyme(s), insoluble basement membrane was labeled with 125I and the release of radioactivity into the supernatant following incubation with extracts of involuting breast indicated hydrolysis of basement membrane. Extracts of breast homogenate extensively hydrolyzed labeled basement membrane if naturally occurring inhibitors were removed by previous washing, whereas liver or kidney extracts prepared in a similar manner were devoid of activity. The hydrolysis of basement membrane was time and concentration dependent and had a pH optimum. The reaction was blocked by prior heating of the extract at 100 degrees C. for 30 minutes, removal of divalent cations, and presence of diisopropylfluorophosphate (a specific serine esterase inhibitor); prolonged dialysis failed to remove the hydrolytic activity. It is concluded that an enzyme system present in the involuting breast is capable of basement membrane hydrolysis", "contents": "Removal of basement membrane in the involuting breast. Morphologic and immunohistochemical studies by light and electron microscopy indicated that basement membrane was removed during the process of involution of the murine breast. Removal of the basement membrane started 2 days postweaning, was maximal at 4 days, and correlated with degeneration of epithelial cells. There was no evidence of phagocytosis of basement membrane, so the removal of this antigen was attributed to enzymatic hydrolysis. To determine the activity of breast homogenate on the specific basement membrane antigen, insoluble basement membrane embedded in agarose gels was incubated with breast liver and kidney homogenates. When basement membrane antigen was demonstrated by the specific antibody, it was found that breast homogenate solubilized basement membrane but liver and kidney failed to solubilize basement membrane. To quantify the reaction and determine some of the characteristics of the responsible enzyme(s), insoluble basement membrane was labeled with 125I and the release of radioactivity into the supernatant following incubation with extracts of involuting breast indicated hydrolysis of basement membrane. Extracts of breast homogenate extensively hydrolyzed labeled basement membrane if naturally occurring inhibitors were removed by previous washing, whereas liver or kidney extracts prepared in a similar manner were devoid of activity. The hydrolysis of basement membrane was time and concentration dependent and had a pH optimum. The reaction was blocked by prior heating of the extract at 100 degrees C. for 30 minutes, removal of divalent cations, and presence of diisopropylfluorophosphate (a specific serine esterase inhibitor); prolonged dialysis failed to remove the hydrolytic activity. It is concluded that an enzyme system present in the involuting breast is capable of basement membrane hydrolysis"}
{"id": "PMID:5634", "title": "The effects of dopamine and isoproterenol on the pulmonary circulation.", "content": "Dopamine and isoproterenol, although used primarily for their inotropic effects, are also potent vasoactive substances. To determine their effects on the pulmonary circulation, we cannulated the left lower lobe bronchus in 20 dogs to permit ventilation with either air or a mixture of 95% nitrogen and 5% carbon dioxide; systemic oxygenation was maintained by venitlating the right lung with 95% oxygen. The lobe was perfused at a controlled flow rate and left atrial pressure was held constant. Hypoxic ventilation increased the lobar vascular resistance by 52% (p less than 0.001). Dopamine infusion (20 mcg. per kilogram per minute) during air ventilation also increased lobar vascular resistance by 50% (p less than 0.001). During hypoxic ventilation, dopamine increased the resistance by an additional 19% (p less than 0.001). In contrast, isoproterenol (0.2 mcg. per kilogram per minute) abolished the hypoxic pressor response (p less than 0.001). Combined alpha- and beta-adrenergic blockade did not alter hypoxia-induced vasoconstriction, whereas phentolamine blocked the dopamine response and propranolol abolished the isoproterenol-induced vasodilation. These results indicate the following: (1) The hypoxic pressor response is independent of sympathetic innervation; (2) dopamine in dogs is a pulmonary vasoconstrictor; and (3) isoproterenol is a pulmonary vasodilator. If these findings can be extrapolated to man, isoproterenol may be the preferred inotropic agent in patients with an elevated pulmonary vascular resistance.", "contents": "The effects of dopamine and isoproterenol on the pulmonary circulation. Dopamine and isoproterenol, although used primarily for their inotropic effects, are also potent vasoactive substances. To determine their effects on the pulmonary circulation, we cannulated the left lower lobe bronchus in 20 dogs to permit ventilation with either air or a mixture of 95% nitrogen and 5% carbon dioxide; systemic oxygenation was maintained by venitlating the right lung with 95% oxygen. The lobe was perfused at a controlled flow rate and left atrial pressure was held constant. Hypoxic ventilation increased the lobar vascular resistance by 52% (p less than 0.001). Dopamine infusion (20 mcg. per kilogram per minute) during air ventilation also increased lobar vascular resistance by 50% (p less than 0.001). During hypoxic ventilation, dopamine increased the resistance by an additional 19% (p less than 0.001). In contrast, isoproterenol (0.2 mcg. per kilogram per minute) abolished the hypoxic pressor response (p less than 0.001). Combined alpha- and beta-adrenergic blockade did not alter hypoxia-induced vasoconstriction, whereas phentolamine blocked the dopamine response and propranolol abolished the isoproterenol-induced vasodilation. These results indicate the following: (1) The hypoxic pressor response is independent of sympathetic innervation; (2) dopamine in dogs is a pulmonary vasoconstrictor; and (3) isoproterenol is a pulmonary vasodilator. If these findings can be extrapolated to man, isoproterenol may be the preferred inotropic agent in patients with an elevated pulmonary vascular resistance."}
{"id": "PMID:5635", "title": "Biochemistry of copper.", "content": "Copper, as a component of numerous cuproenzymes, plays a vital role in many physiologic functions in man and animals. From the stand-point of human health there are at least three functional areas of prime importance. Copper is involved in the development and maintenance of cardiovascular and skeletal integrity, central nervous system structure and function, and erythropoietic function including iron metabolism. Although there is no evidence for widespread copper deficiency in the human population, it does occur, owing to genetic defects and other precipitating factors. A clear understanding of the functions of copper and its mechanisms of action could prove highly beneficial in the solution of present and unforeseen problems in medicine.", "contents": "Biochemistry of copper. Copper, as a component of numerous cuproenzymes, plays a vital role in many physiologic functions in man and animals. From the stand-point of human health there are at least three functional areas of prime importance. Copper is involved in the development and maintenance of cardiovascular and skeletal integrity, central nervous system structure and function, and erythropoietic function including iron metabolism. Although there is no evidence for widespread copper deficiency in the human population, it does occur, owing to genetic defects and other precipitating factors. A clear understanding of the functions of copper and its mechanisms of action could prove highly beneficial in the solution of present and unforeseen problems in medicine."}
{"id": "PMID:5644", "title": "Effects of dietary saturated and trans fatty acids on cholesteryl ester synthesis and hydrolysis in the testes of rats.", "content": "Studies were made of the enzymic synthesis and hydrolysis of cholesteryl esters in rat testes. Weanling rats were fed for 14 weeks diets containing 5% by wt of hydrogenated coconut oil (HCO), a concentrate of ethyl elaidate and linolelaidate (TRANS), devoid of essential fatty acids (EFA), or safflower oil (SAFF). Cholesterol esterifying activity was localized in the soluble fraction, and cholesteryl ester hydrolase activity was distributed in both particulate and soluble fractions obtained from tissue homogenates. The optimum pH was 6.0 for esterification and 6.9-7.0 for hydrolysis. Neither esterifying nor hydrolytic activity was affected by freezing and thawing, but both reactions were inhibited by heat or sonication. The animals of both the HCO and TRANS groups had developed an EFA deficiency before they were sacrificed. The EFA deficiency produced upon feeding the HCO diet had no apparent effect on the synthesis and hydrolysis of cholesteryl esters in rat testes. The TRANS diet influenced the development of the testes as judged by their size, and cholesterol esterifying and cholesteryl ester hydrolyzing activities were suppressed in the testes of the animals of this group. A major difference in the effects of the HCO and TRANS diets on the lipids of the tests was the relatively minor amount of eicosatrienoic acid (20:3) and the elevated level of docosapentaenoic acid (22:5) in the cholesteryl esters of the testicular lipids of the TRANS group.", "contents": "Effects of dietary saturated and trans fatty acids on cholesteryl ester synthesis and hydrolysis in the testes of rats. Studies were made of the enzymic synthesis and hydrolysis of cholesteryl esters in rat testes. Weanling rats were fed for 14 weeks diets containing 5% by wt of hydrogenated coconut oil (HCO), a concentrate of ethyl elaidate and linolelaidate (TRANS), devoid of essential fatty acids (EFA), or safflower oil (SAFF). Cholesterol esterifying activity was localized in the soluble fraction, and cholesteryl ester hydrolase activity was distributed in both particulate and soluble fractions obtained from tissue homogenates. The optimum pH was 6.0 for esterification and 6.9-7.0 for hydrolysis. Neither esterifying nor hydrolytic activity was affected by freezing and thawing, but both reactions were inhibited by heat or sonication. The animals of both the HCO and TRANS groups had developed an EFA deficiency before they were sacrificed. The EFA deficiency produced upon feeding the HCO diet had no apparent effect on the synthesis and hydrolysis of cholesteryl esters in rat testes. The TRANS diet influenced the development of the testes as judged by their size, and cholesterol esterifying and cholesteryl ester hydrolyzing activities were suppressed in the testes of the animals of this group. A major difference in the effects of the HCO and TRANS diets on the lipids of the tests was the relatively minor amount of eicosatrienoic acid (20:3) and the elevated level of docosapentaenoic acid (22:5) in the cholesteryl esters of the testicular lipids of the TRANS group."}
{"id": "PMID:5648", "title": "Defective lipid disposal mechanisms during bacterial infection in rhesus monkeys.", "content": "Mechanisms producing hypertriglyceridemia during bacterial sepsis have not been well defined. In this study lipid disposal mechanisms were assessed in 76 infected and 19 control male rhesus monkeys by the ability to dispose of triglycerides after: (1) oral lipid loading; (2) intravenous lipid loading; and (3) by lipolytic enzyme activity tests as measured by postheparin lipolytic activity (PHLA). Studies were performed both before and 48 hr after intravenous inoculation with either Salmonella typhimurium or Diplococcus pneumoniae when illness was uniformly severe and fasting serum triglyceride elevations were increased maximally. S. typhimurium-infected monkeys demonstrated significant fasting hypertriglyceridemia (p is less than 0.001), reduced clearance of orally and intravenously administered lipid and markedly reduced PHLA. During this gram-negative sepsis, mild lethargy, slight diarrhea, and a 2% mortality were observed. During D. pneumoniae sepsis, average fasting triglyceride concentrations were slightly, but not significantly elevated. While oral lipid clearance was impaired, intravenous lipid clearance was unimpaired, and PHLA was slightly reduced. Marked lethargy, agitation, and a 20% mortality were present during this gram-positive infection. Results of this study support the concept that an impairment of lipid disposal mechanisms, particularly during gram-negative sepsis with S. typhimurium, may significantly contribute to the observed hypertriglyceridemia.", "contents": "Defective lipid disposal mechanisms during bacterial infection in rhesus monkeys. Mechanisms producing hypertriglyceridemia during bacterial sepsis have not been well defined. In this study lipid disposal mechanisms were assessed in 76 infected and 19 control male rhesus monkeys by the ability to dispose of triglycerides after: (1) oral lipid loading; (2) intravenous lipid loading; and (3) by lipolytic enzyme activity tests as measured by postheparin lipolytic activity (PHLA). Studies were performed both before and 48 hr after intravenous inoculation with either Salmonella typhimurium or Diplococcus pneumoniae when illness was uniformly severe and fasting serum triglyceride elevations were increased maximally. S. typhimurium-infected monkeys demonstrated significant fasting hypertriglyceridemia (p is less than 0.001), reduced clearance of orally and intravenously administered lipid and markedly reduced PHLA. During this gram-negative sepsis, mild lethargy, slight diarrhea, and a 2% mortality were observed. During D. pneumoniae sepsis, average fasting triglyceride concentrations were slightly, but not significantly elevated. While oral lipid clearance was impaired, intravenous lipid clearance was unimpaired, and PHLA was slightly reduced. Marked lethargy, agitation, and a 20% mortality were present during this gram-positive infection. Results of this study support the concept that an impairment of lipid disposal mechanisms, particularly during gram-negative sepsis with S. typhimurium, may significantly contribute to the observed hypertriglyceridemia."}
{"id": "PMID:5643", "title": "Sweetening agents from natural sources.", "content": "Sweetness is an important taste sensation to humans. The absence of suitable sweeteners as alternatives to cyclamates and saccharin has led to a renewed interest in sweeteners form natural sources. A brief review of the history of sweetener usage provides a basis for understanding our present heavy consumption of sweet substances. The structure of naturally-occurring compounds possessing a sweet taste range from simple sugars to complex, intensely sweet proteins. The structural types include monoterpenes, diterpenes, triterpenes, flavonoids, steroid saponins, dipeptides, and proteins. Some of these substances are not, strictly-speaking, natural but are derived from natural sources by relatively minor chemical modification. The properties of two non-sweet substances, miraculin and gymnemic acid, are included because of their close relationship to the subject of sweeteners. Miraculin causes sour substances to taste sweet and gymnemic acid selectively blocks sweet taste perception. The second part of the paper presents some of the work on monellin, the intensely sweet protein from \"serendipity berries\" (Dioscoreophyllum cumminsii). The physico-chemical studies of monellin provide convincing evidence that it is, indeed, a protein. Structural studies using denaturants and specific chemical modifications have provided a beginning of our understanding of the molecular basis of the sweet taste of monellin.", "contents": "Sweetening agents from natural sources. Sweetness is an important taste sensation to humans. The absence of suitable sweeteners as alternatives to cyclamates and saccharin has led to a renewed interest in sweeteners form natural sources. A brief review of the history of sweetener usage provides a basis for understanding our present heavy consumption of sweet substances. The structure of naturally-occurring compounds possessing a sweet taste range from simple sugars to complex, intensely sweet proteins. The structural types include monoterpenes, diterpenes, triterpenes, flavonoids, steroid saponins, dipeptides, and proteins. Some of these substances are not, strictly-speaking, natural but are derived from natural sources by relatively minor chemical modification. The properties of two non-sweet substances, miraculin and gymnemic acid, are included because of their close relationship to the subject of sweeteners. Miraculin causes sour substances to taste sweet and gymnemic acid selectively blocks sweet taste perception. The second part of the paper presents some of the work on monellin, the intensely sweet protein from \"serendipity berries\" (Dioscoreophyllum cumminsii). The physico-chemical studies of monellin provide convincing evidence that it is, indeed, a protein. Structural studies using denaturants and specific chemical modifications have provided a beginning of our understanding of the molecular basis of the sweet taste of monellin."}
{"id": "PMID:5650", "title": "[Mendelson's syndrome (author's transl)].", "content": "It is reported on 10 patients with the features of Mendelson's syndrome; 4 patients died. Diagnosis, therapy, course and prognosis of this severe complication following aspiration of gastric hydrochloric acid are discussed.", "contents": "[Mendelson's syndrome (author's transl)]. It is reported on 10 patients with the features of Mendelson's syndrome; 4 patients died. Diagnosis, therapy, course and prognosis of this severe complication following aspiration of gastric hydrochloric acid are discussed."}
{"id": "PMID:5649", "title": "The effects of nalorphine and naloxone on maternal and fetal blood gas and pH.", "content": "In the control trials on near-term pregnant women before the onset of labour, nalorphine was found to cause a mild respiratory acidosis in the mother and metabolic acidosis in the fetus. These effects were not apparent when naloxone was administered.", "contents": "The effects of nalorphine and naloxone on maternal and fetal blood gas and pH. In the control trials on near-term pregnant women before the onset of labour, nalorphine was found to cause a mild respiratory acidosis in the mother and metabolic acidosis in the fetus. These effects were not apparent when naloxone was administered."}
{"id": "PMID:5651", "title": "[Investigations of the lipase activity of a pancreatin compound (author's transl)].", "content": "In connection with the physiologic process of digestion, the requirements for an enzyme-based drug are stated. Quick release of highly active enzymes in the duodenum is a prerequisite of physiological stimulation of the pancreatic excretory function. Digestive potency is regarded as a suitable gauge for comparing of results in large-scale in vitro scanning. Our own in vitro and in vivo studies have borne out the possibility of transferring in vitro findings to the therapeutic value of this compound. As shown by our investigations, quick release of highly active enzymes in vitro is coupled with a high degree of bioavailability in Fermento duodenal. As a result, normalization or reduction of the lipid content of faeces--as a sign of therapeutic efficacy--is seen in patients with pancreatic excretory insufficiency. Statistical evaluation resulted in the following: 1 A statistically significant (p less than 0.1%) increase in lipase activity in the duodenal juice in vitro after addition of one capsule of Fermento duodenal. 2. Lipase activity in vivo after 15 minutes is significantly different from all other values. 3. A statistically significant (p less than 1%) drop in the amount and lipid content of faeces following the treatment with Fermento duodenal.", "contents": "[Investigations of the lipase activity of a pancreatin compound (author's transl)]. In connection with the physiologic process of digestion, the requirements for an enzyme-based drug are stated. Quick release of highly active enzymes in the duodenum is a prerequisite of physiological stimulation of the pancreatic excretory function. Digestive potency is regarded as a suitable gauge for comparing of results in large-scale in vitro scanning. Our own in vitro and in vivo studies have borne out the possibility of transferring in vitro findings to the therapeutic value of this compound. As shown by our investigations, quick release of highly active enzymes in vitro is coupled with a high degree of bioavailability in Fermento duodenal. As a result, normalization or reduction of the lipid content of faeces--as a sign of therapeutic efficacy--is seen in patients with pancreatic excretory insufficiency. Statistical evaluation resulted in the following: 1 A statistically significant (p less than 0.1%) increase in lipase activity in the duodenal juice in vitro after addition of one capsule of Fermento duodenal. 2. Lipase activity in vivo after 15 minutes is significantly different from all other values. 3. A statistically significant (p less than 1%) drop in the amount and lipid content of faeces following the treatment with Fermento duodenal."}
{"id": "PMID:5665", "title": "Characterisation of eukaryotic ribosomal proteins.", "content": "A simple method of two-dimensional polyacrylamide gel electrophoresis is described which affords: (1) high resolution of eukaryotic ribosomal proteins; (2) good recovery of protein in the transfer from first to second dimension; and (3) characterisation of the separated proteins in terms of molecular weights and other electrophoretic properties. Using this method, we have characterised 70 proteins in rabbit reticulocyte ribosomes, 30 from the small subunit and 40 from the large subunit. The molecular weight distribution is compared with those obtained by other authors after fractionation of the proteins in two dimensions.", "contents": "Characterisation of eukaryotic ribosomal proteins. A simple method of two-dimensional polyacrylamide gel electrophoresis is described which affords: (1) high resolution of eukaryotic ribosomal proteins; (2) good recovery of protein in the transfer from first to second dimension; and (3) characterisation of the separated proteins in terms of molecular weights and other electrophoretic properties. Using this method, we have characterised 70 proteins in rabbit reticulocyte ribosomes, 30 from the small subunit and 40 from the large subunit. The molecular weight distribution is compared with those obtained by other authors after fractionation of the proteins in two dimensions."}
{"id": "PMID:5666", "title": "Study on proteins from yeast cytoplasmic ribosomes by two-dimensional gel electrophoresis.", "content": "Proteins of yeast cytoplasmic ribosomes were analyzed by two different methods of two dimensional gel electrophoresis: run at pH 8.6 in 1-D1 and at pH 4.6 in 2-D (Method A); run at pH 5.0 in 1-D and in the presence of sodium dodecyl sulfate in 2-D (Method B). The numbers of proteins estimated were 28 (Method A) and 29 or 30 (Method B) in the 40S small subunit, and 40 (Method A) and 41 (Method B) in the 60S large subunit, respectively. Molecular weights of proteins in the small and the large subunits were found to be less than 40,000 and 60,000 respectively.", "contents": "Study on proteins from yeast cytoplasmic ribosomes by two-dimensional gel electrophoresis. Proteins of yeast cytoplasmic ribosomes were analyzed by two different methods of two dimensional gel electrophoresis: run at pH 8.6 in 1-D1 and at pH 4.6 in 2-D (Method A); run at pH 5.0 in 1-D and in the presence of sodium dodecyl sulfate in 2-D (Method B). The numbers of proteins estimated were 28 (Method A) and 29 or 30 (Method B) in the 40S small subunit, and 40 (Method A) and 41 (Method B) in the 60S large subunit, respectively. Molecular weights of proteins in the small and the large subunits were found to be less than 40,000 and 60,000 respectively."}
{"id": "PMID:5667", "title": "Conformational changes in cytochrome aa3 and ATP synthetase of the mitochondrial membrane and their role in mitochondrial energy transduction.", "content": "1. The thermodynamics and molecular basis of energy-linked conformational changes in the cytochrome aa3 and ATP synthetase complexes of the mitochondrial membrane have been studied with spectrophotometrical and fluorometrical techniques. 2. Ferric cytochrome aa3 exists in two conformations, high spin and low spin, the equilibrium between these states being controlled by the electrical potential difference across the mitochondrial membrane. The conformational change is brought about by an electrical field-driven binding of one proton per aa3 to the complex. At pH 7.2 the concentration of the two conformations is equal at a membrane potential of 170 mV corresponding to about 4 kcal/mole. 3. The high to low spin transition in ferric aa3 is also induced by hydrolysis of ATP in which case two molecules of aa3 are shifted per ATP molecule hydrolyzed. This is in accordance with translocation of two protons across the mitochondrial membrane coupled to hydrolysis of ATP as proposed in the chemiosmotic theory of oxidative phosphorylation. 4. The conformational transition in cytochrome aa3 is not an expression of the formation of a 'high-energy' intermediate or reversal of the energy-transducing pathway of oxidative phosphorylation, but is presumably the basis of allosteric control of the activity of cytochrome oxidase by the energy state of the mitochondrion. This control is exerted by a regulatory mechanism in which the electrical potential difference controls the conformation and redox properties of the heme centres and thereby the rate of oxygen consumption. 5. The synthesis of one molecule of ATP by oxidative phosphorylation is energetically equivalent to the work done in carrying two electrical charges across the entire mitochondrial membrane. 6. Fluorescence changes of aurovertin bound to ATP synthetase reveal that the electrical membrane potential induces a conformational change in the F1 portion of the enzyme which is probably associated with dissociation of the natural F1 inhibitor protein. This conformational change is energetically equivalent to the work done in carrying one electrical charge across the mitochondrial membrane. 7. A model is proposed for the mechanism of the electrical field-induced conformational changes in the cytochrome aa3 and ATP synthetase complexes, and the significance of these changes in the mechanism and control of mitochondrial energy conservation is discussed.", "contents": "Conformational changes in cytochrome aa3 and ATP synthetase of the mitochondrial membrane and their role in mitochondrial energy transduction. 1. The thermodynamics and molecular basis of energy-linked conformational changes in the cytochrome aa3 and ATP synthetase complexes of the mitochondrial membrane have been studied with spectrophotometrical and fluorometrical techniques. 2. Ferric cytochrome aa3 exists in two conformations, high spin and low spin, the equilibrium between these states being controlled by the electrical potential difference across the mitochondrial membrane. The conformational change is brought about by an electrical field-driven binding of one proton per aa3 to the complex. At pH 7.2 the concentration of the two conformations is equal at a membrane potential of 170 mV corresponding to about 4 kcal/mole. 3. The high to low spin transition in ferric aa3 is also induced by hydrolysis of ATP in which case two molecules of aa3 are shifted per ATP molecule hydrolyzed. This is in accordance with translocation of two protons across the mitochondrial membrane coupled to hydrolysis of ATP as proposed in the chemiosmotic theory of oxidative phosphorylation. 4. The conformational transition in cytochrome aa3 is not an expression of the formation of a 'high-energy' intermediate or reversal of the energy-transducing pathway of oxidative phosphorylation, but is presumably the basis of allosteric control of the activity of cytochrome oxidase by the energy state of the mitochondrion. This control is exerted by a regulatory mechanism in which the electrical potential difference controls the conformation and redox properties of the heme centres and thereby the rate of oxygen consumption. 5. The synthesis of one molecule of ATP by oxidative phosphorylation is energetically equivalent to the work done in carrying two electrical charges across the entire mitochondrial membrane. 6. Fluorescence changes of aurovertin bound to ATP synthetase reveal that the electrical membrane potential induces a conformational change in the F1 portion of the enzyme which is probably associated with dissociation of the natural F1 inhibitor protein. This conformational change is energetically equivalent to the work done in carrying one electrical charge across the mitochondrial membrane. 7. A model is proposed for the mechanism of the electrical field-induced conformational changes in the cytochrome aa3 and ATP synthetase complexes, and the significance of these changes in the mechanism and control of mitochondrial energy conservation is discussed."}
{"id": "PMID:5668", "title": "[Old and new dangers of blood transfusion (author's transl)].", "content": "The predominant danger of blood transfusion, even after the discovery of the ABO and Rh systems, is the immunological risk. This led in 1940 to a regulation of blood transfusion in Germany by official guidelines which were constantly adjusted in the light of new research results. The dangers due to deterioration on storage still receive too little attention although these may be of greater danger to the patient than immunisation risk. Also the assessment of other medical problems of transfusion is insufficiently applied to clinical routine.", "contents": "[Old and new dangers of blood transfusion (author's transl)]. The predominant danger of blood transfusion, even after the discovery of the ABO and Rh systems, is the immunological risk. This led in 1940 to a regulation of blood transfusion in Germany by official guidelines which were constantly adjusted in the light of new research results. The dangers due to deterioration on storage still receive too little attention although these may be of greater danger to the patient than immunisation risk. Also the assessment of other medical problems of transfusion is insufficiently applied to clinical routine."}
{"id": "PMID:5669", "title": "Vinyl chloride dependent mutagensis: effects of liver extracts and free radicals.", "content": "The mutagenic effects of vinyl chloride (VC) on Salmonella typhimurium strain TA1530 are enhanced by mouse or rat liver extracts. The extracts prepared from mice pretreated either with vinyl chloride or the microsomal enzyme inducer, Aroclor 1254, did not produce any greater stimulation of VC-dependent mutagenesis than extracts from untreated animals. These same extracts, however, differed markedly in their capacity to stimulate the mutagenicity of dimethylnitrosamine (DMN), a compound which is converted to a mutagen by an NADPH dependent microsomal mixed function oxidase. The order of activity of the extracts with DMN was Aroclor pretreated is greater than untreated is greater than VC pretreated. Furthermore, the stimulatory effect of the liver extracts on VC mediated mutagenesis did not require NADPH and was still evident in liver extracts in which the microsomal mixed function oxidase system had been heat inactivated. The mutagenic activity of VC also was found to be stimulated by riboflavin in the presence of light suggesting that free radicals may be involved in VC dependent mutagenesis.", "contents": "Vinyl chloride dependent mutagensis: effects of liver extracts and free radicals. The mutagenic effects of vinyl chloride (VC) on Salmonella typhimurium strain TA1530 are enhanced by mouse or rat liver extracts. The extracts prepared from mice pretreated either with vinyl chloride or the microsomal enzyme inducer, Aroclor 1254, did not produce any greater stimulation of VC-dependent mutagenesis than extracts from untreated animals. These same extracts, however, differed markedly in their capacity to stimulate the mutagenicity of dimethylnitrosamine (DMN), a compound which is converted to a mutagen by an NADPH dependent microsomal mixed function oxidase. The order of activity of the extracts with DMN was Aroclor pretreated is greater than untreated is greater than VC pretreated. Furthermore, the stimulatory effect of the liver extracts on VC mediated mutagenesis did not require NADPH and was still evident in liver extracts in which the microsomal mixed function oxidase system had been heat inactivated. The mutagenic activity of VC also was found to be stimulated by riboflavin in the presence of light suggesting that free radicals may be involved in VC dependent mutagenesis."}
{"id": "PMID:5671", "title": "Testicular function after orchiopexy for unilaterally undescended testis.", "content": "Testicular function was determined in 29 men, 21 to 35 years old, who had undergone orchiopexy for unilaterally undescended testis at four to 12 years of age. Serum testosterone and dialyzable testosterone concentrations of these men were not significantly different from those of a control group of 30 normal men, and their basal serum luteinizing hormone concentrations and serum luteinizing hormone responses to synthetic gonadotropin-releasing hormone were only slightly higher than those of the normal men. The mean sperm density of the patients, however, was only one third of that of the normal men (p less than 0.001). The mean serum follicle stimulating hormone response ro gonadotropin-releasing hormone of the patients was doubled that of the normal men (p less than 0.001). The data indicate that spermatogenesis may be abnormal after orchipexy, and suggest that men with unilaterally undescended testis may have bilateral testicular abnormality.", "contents": "Testicular function after orchiopexy for unilaterally undescended testis. Testicular function was determined in 29 men, 21 to 35 years old, who had undergone orchiopexy for unilaterally undescended testis at four to 12 years of age. Serum testosterone and dialyzable testosterone concentrations of these men were not significantly different from those of a control group of 30 normal men, and their basal serum luteinizing hormone concentrations and serum luteinizing hormone responses to synthetic gonadotropin-releasing hormone were only slightly higher than those of the normal men. The mean sperm density of the patients, however, was only one third of that of the normal men (p less than 0.001). The mean serum follicle stimulating hormone response ro gonadotropin-releasing hormone of the patients was doubled that of the normal men (p less than 0.001). The data indicate that spermatogenesis may be abnormal after orchipexy, and suggest that men with unilaterally undescended testis may have bilateral testicular abnormality."}
{"id": "PMID:5674", "title": "[Isolation and characterization of main albumin fractions of seeds from sunflower (Helianthus annuus L.) and rape (Brassica napus L.)].", "content": "The main fractions of the albumins from sunflower and rapeseeds (isolated by means of precipitation with ammonium sulphate or tannin + caffeine and subsequent gel chromatography) are low-molecular, very basic proteins. Their molecular weights range from 10 000 to 16 000, and their isoelectric points (determined by isoelectric focusing and free electrophoresis) are situated at pH greater than 10.0. From the circular dichroism in the wavelength range from 200 to 240 nm it is deduced that the main fraction of the rape albumin is a well-structured protein with 40-46% alpha-helix in aqueous and salt-containing solutions. Denaturation by heating is achieved only at temperatures about 100 degrees C and pH values greater than 9. 20% alpha-helix are left after the action of 8 M urea. This conformational stability is explained by the presence of disulphide linkages in the molecule.", "contents": "[Isolation and characterization of main albumin fractions of seeds from sunflower (Helianthus annuus L.) and rape (Brassica napus L.)]. The main fractions of the albumins from sunflower and rapeseeds (isolated by means of precipitation with ammonium sulphate or tannin + caffeine and subsequent gel chromatography) are low-molecular, very basic proteins. Their molecular weights range from 10 000 to 16 000, and their isoelectric points (determined by isoelectric focusing and free electrophoresis) are situated at pH greater than 10.0. From the circular dichroism in the wavelength range from 200 to 240 nm it is deduced that the main fraction of the rape albumin is a well-structured protein with 40-46% alpha-helix in aqueous and salt-containing solutions. Denaturation by heating is achieved only at temperatures about 100 degrees C and pH values greater than 9. 20% alpha-helix are left after the action of 8 M urea. This conformational stability is explained by the presence of disulphide linkages in the molecule."}
{"id": "PMID:5676", "title": "[Effect of acid polysaccharides on properties of pancreatic proteases].", "content": "The use of acid polysaccharides (sodium alginate, pectin, carrageenan, etc.) as gel-forming agents in the manufacture of artificial foods excites the interest in the study of their effects on the enzymes of the gastrointestinal tract. In this connection, the authors investigated the action of various acid polysaccharides on the kinetics of the hydrolysis of low-molecular substrates catalyzed by pancreatic proteinases. It was shown that the intereactions between acid polysaccharides and enzymes produce effects which can be fully explained by changes in the apparent ionization constants of the ionogenic groups which participate in the catalytic reaction. The extent of the effects observed in presumably determined by the strength of the electrostatic potential which is generated by polyanions.", "contents": "[Effect of acid polysaccharides on properties of pancreatic proteases]. The use of acid polysaccharides (sodium alginate, pectin, carrageenan, etc.) as gel-forming agents in the manufacture of artificial foods excites the interest in the study of their effects on the enzymes of the gastrointestinal tract. In this connection, the authors investigated the action of various acid polysaccharides on the kinetics of the hydrolysis of low-molecular substrates catalyzed by pancreatic proteinases. It was shown that the intereactions between acid polysaccharides and enzymes produce effects which can be fully explained by changes in the apparent ionization constants of the ionogenic groups which participate in the catalytic reaction. The extent of the effects observed in presumably determined by the strength of the electrostatic potential which is generated by polyanions."}
{"id": "PMID:5677", "title": "[Interaction between proteins and acid polysaccharides].", "content": "The intereaction between proteins and acid polysaccharides is electrostatic in nature and leads to the formation of soluble charged and insoluble neutral complexes. The complex formation in the system casein-dextran sulphate is followed by means of turbidimetric titration. It depends on the pH value and the electrolyte concentration. On free electrophoresis, complexes formed below the isoelectric point of the protein exhibit anodic mobility, whereas pure casein migrates to the cathode. The protein in the complex is not able to bind amido black. Consequently, it cannot be detected electrophoretically by dyebinding. The results from viscosity and diffusion measurements are indicative of an increased hydrodynamic volume of the complexes.", "contents": "[Interaction between proteins and acid polysaccharides]. The intereaction between proteins and acid polysaccharides is electrostatic in nature and leads to the formation of soluble charged and insoluble neutral complexes. The complex formation in the system casein-dextran sulphate is followed by means of turbidimetric titration. It depends on the pH value and the electrolyte concentration. On free electrophoresis, complexes formed below the isoelectric point of the protein exhibit anodic mobility, whereas pure casein migrates to the cathode. The protein in the complex is not able to bind amido black. Consequently, it cannot be detected electrophoretically by dyebinding. The results from viscosity and diffusion measurements are indicative of an increased hydrodynamic volume of the complexes."}
{"id": "PMID:5678", "title": "[Isolation of proteins with complex forming agents].", "content": "Taking vegetable albumins for models, the authors report of the possibilities of isolating proteins (which cannot be precipitated isoelectrically) by using their property of forming complexes with tannin or poly-anions. The precipitation of proteins with dextran sulphate or polyphosphates, which is due to electrostatic interaction, depends on the pH value and the electrolyte content of the solution. Under appropriate experimental conditions, protein yields of 100% are achieved. By means of tannin, the proteins are completely precipitated in a wide range of pH. The protein component of the poly-anion-containing complexes is isolated by precipitation with salt or by thermal coagulation after dissolving of the complexes. The isolation of protein from the tannin complexes is preferably realized by reaction with coffeine.", "contents": "[Isolation of proteins with complex forming agents]. Taking vegetable albumins for models, the authors report of the possibilities of isolating proteins (which cannot be precipitated isoelectrically) by using their property of forming complexes with tannin or poly-anions. The precipitation of proteins with dextran sulphate or polyphosphates, which is due to electrostatic interaction, depends on the pH value and the electrolyte content of the solution. Under appropriate experimental conditions, protein yields of 100% are achieved. By means of tannin, the proteins are completely precipitated in a wide range of pH. The protein component of the poly-anion-containing complexes is isolated by precipitation with salt or by thermal coagulation after dissolving of the complexes. The isolation of protein from the tannin complexes is preferably realized by reaction with coffeine."}
{"id": "PMID:5679", "title": "[Technological directions for processing rape proteins into protein concentrates and isolates].", "content": "Rape-seeds or rape-seed meal are relatively cheap, but valuable raw materials for the manufacture of protein concentrates and isolates which may be used as constituents of foodstuffs. The high content of crude fibres and also of thioglucosides leads to considerable difficulties in the development of techniques for the manufacture of high-grade protein preparations. To describe the procedure, certain production-technological properties of rape proteins are discussed, such as extraction parameters, coagulating conditions, processing temperature, amount of solvent, etc. On the basis of these data, the following techniques for the manufacture of rape protein products are presented: - protein concentration by means of the water diffusion method; - protein isolation with the aid of one or multi-stage extraction. Finally, the author reports of a fermenting procedure for the manufacture of protein biomass from coarse colza meal. Furthermore, he presents some data about the nutritional value of rape protein.", "contents": "[Technological directions for processing rape proteins into protein concentrates and isolates]. Rape-seeds or rape-seed meal are relatively cheap, but valuable raw materials for the manufacture of protein concentrates and isolates which may be used as constituents of foodstuffs. The high content of crude fibres and also of thioglucosides leads to considerable difficulties in the development of techniques for the manufacture of high-grade protein preparations. To describe the procedure, certain production-technological properties of rape proteins are discussed, such as extraction parameters, coagulating conditions, processing temperature, amount of solvent, etc. On the basis of these data, the following techniques for the manufacture of rape protein products are presented: - protein concentration by means of the water diffusion method; - protein isolation with the aid of one or multi-stage extraction. Finally, the author reports of a fermenting procedure for the manufacture of protein biomass from coarse colza meal. Furthermore, he presents some data about the nutritional value of rape protein."}
{"id": "PMID:5680", "title": "[Mass transfer in production of milk protein coprecipitates].", "content": "During the last twenty years heat coagulation has become a more important technical procedure for the isolation of milk proteins because of its very efficient utilization of raw material. Experiments are reported to get approximation equations for the mass transfer in the production of milk protein coprecipitates from skim milk and mixtures of skim milk with rennet and acid whey by means of statistical planning and interpreting of experiments. Good exactness was reached. The coagula consist of casein fractions, whey protein fractions, calcium, and phosphates. The products are thermically rather stable, sensorically indifferent and contain water insoluble protein. They are suitable to improve the fat: protein ration of sausages, but also for the protein enrichment of other foods and for dietetic purposes.", "contents": "[Mass transfer in production of milk protein coprecipitates]. During the last twenty years heat coagulation has become a more important technical procedure for the isolation of milk proteins because of its very efficient utilization of raw material. Experiments are reported to get approximation equations for the mass transfer in the production of milk protein coprecipitates from skim milk and mixtures of skim milk with rennet and acid whey by means of statistical planning and interpreting of experiments. Good exactness was reached. The coagula consist of casein fractions, whey protein fractions, calcium, and phosphates. The products are thermically rather stable, sensorically indifferent and contain water insoluble protein. They are suitable to improve the fat: protein ration of sausages, but also for the protein enrichment of other foods and for dietetic purposes."}
{"id": "PMID:5686", "title": "[The effect of novocaine on the electrical activity of nodes of Ranvier in high  and low pH solutions].", "content": "The minimal concentrations of procaine which block the action potentials of a single Ranvier node were determined under decreased and increased pH in the bathing solution. The changes in concentrations of the basic [B] and cationic [BH+] form of procaine with pH were of monotonic character: [B] drops and [BH+] grows with pH increase. The dependence of membrane excitability (fraction of channels are able to excite)  on pH was nonmonotonic; it is low under increased and decreased pH. On the basis of these data the hypothesis that the membrane of the Ranvier node may interact with a definite form of procaine is rejected. T he quantitative analysis shows that the membrane interacts with both the basic and cationic forms of procaine but the efficiency of this interaction is different.", "contents": "[The effect of novocaine on the electrical activity of nodes of Ranvier in high  and low pH solutions]. The minimal concentrations of procaine which block the action potentials of a single Ranvier node were determined under decreased and increased pH in the bathing solution. The changes in concentrations of the basic [B] and cationic [BH+] form of procaine with pH were of monotonic character: [B] drops and [BH+] grows with pH increase. The dependence of membrane excitability (fraction of channels are able to excite)  on pH was nonmonotonic; it is low under increased and decreased pH. On the basis of these data the hypothesis that the membrane of the Ranvier node may interact with a definite form of procaine is rejected. T he quantitative analysis shows that the membrane interacts with both the basic and cationic forms of procaine but the efficiency of this interaction is different."}
{"id": "PMID:5687", "title": "[The effect of the pH of the external solution on posttetanic hyperpolarization of a denuded nerve].", "content": "A decrease in pH of the external solution from 7.3 to 5.3 causes an increase in post-tetanic hyperpolarization, while an increase in pH to 9 causes its decrease. The time-course of the hyperpolarization was increased at low pH and reduced at high pH. The possibility of a change in the electrogenicity  of the sodium pump induced by changes in pH is discussed.", "contents": "[The effect of the pH of the external solution on posttetanic hyperpolarization of a denuded nerve]. A decrease in pH of the external solution from 7.3 to 5.3 causes an increase in post-tetanic hyperpolarization, while an increase in pH to 9 causes its decrease. The time-course of the hyperpolarization was increased at low pH and reduced at high pH. The possibility of a change in the electrogenicity  of the sodium pump induced by changes in pH is discussed."}
{"id": "PMID:5688", "title": "Kinetics of thymus-derived lymphocyte count changes in rats affected by graft-versus-host reaction.", "content": "The effect of GVHR on thymus-dependent lymphocytes of various lymphoid organs has been followed autoradiographically and by scintillation technique in a temporal dependence on the induction of the reaction. GVHR was induced in (BD X Lw) F1 hybrid rats with parental spleen (BD) cells. As marker of the thymus-dependent lymphocytes the in vitro 3H-uridine incorporation was used. Compared to B cells, T lymphocytes of rats have a higher ability of incorporating labeled uridine. T lymphocytes in peripheral blood and the thoracic duct achieved their peak at 3 or 4 days following GVHR induction. On the fourth day, simultaneously with a GVH-altered thymus a rapid decline in the number of these cells was also observed. A mobilization of T lymphocytes from the spleen and lymph nodes into the circulation already in the very first days of the reaction might be responsible for the peak seen in PBL and TDL. The GVH-alteration lasting 21 days caused an evident reduction of thymus-dependent lymphocytes in all the organs studied here. The immunological attack of GVHR is considered to be primarily responsible for the exhaustion of T cells. The discussion bears on the possibility of a more progressive action of GVHR on the more mature T lymphocyte subpopulation.", "contents": "Kinetics of thymus-derived lymphocyte count changes in rats affected by graft-versus-host reaction. The effect of GVHR on thymus-dependent lymphocytes of various lymphoid organs has been followed autoradiographically and by scintillation technique in a temporal dependence on the induction of the reaction. GVHR was induced in (BD X Lw) F1 hybrid rats with parental spleen (BD) cells. As marker of the thymus-dependent lymphocytes the in vitro 3H-uridine incorporation was used. Compared to B cells, T lymphocytes of rats have a higher ability of incorporating labeled uridine. T lymphocytes in peripheral blood and the thoracic duct achieved their peak at 3 or 4 days following GVHR induction. On the fourth day, simultaneously with a GVH-altered thymus a rapid decline in the number of these cells was also observed. A mobilization of T lymphocytes from the spleen and lymph nodes into the circulation already in the very first days of the reaction might be responsible for the peak seen in PBL and TDL. The GVH-alteration lasting 21 days caused an evident reduction of thymus-dependent lymphocytes in all the organs studied here. The immunological attack of GVHR is considered to be primarily responsible for the exhaustion of T cells. The discussion bears on the possibility of a more progressive action of GVHR on the more mature T lymphocyte subpopulation."}
{"id": "PMID:5692", "title": "Effect of chlorogenic acid in a casein diet for rats. Nutritional and pathological observations.", "content": "3-week-old male rats were fed on a casein diet containing 1% (w/w) of chlorogenic acid in order to find out if the ingestion of chlorogenic acid may be associated with a reduced utilization of dietary proteins or with causing other adverse effects. The protein efficiency ratio, biological value and digestibility of this diet did not differ from a corresponding casein diet free from chlorogenic acid. No change was observed in the nitrogen balance of the experimental rats. Neither did the rats show any change in hematological values or volumes and pH of the urine. Some deviation was noticed in the weights of kidneys and adrenals of the chlorogec acid-free casein diet. The findings that were made were normal in the microscopic examinations of various organs. Chlorogenic acid did not seem to influence the ultrastructure of the liver as revealed by electron microscopy.", "contents": "Effect of chlorogenic acid in a casein diet for rats. Nutritional and pathological observations. 3-week-old male rats were fed on a casein diet containing 1% (w/w) of chlorogenic acid in order to find out if the ingestion of chlorogenic acid may be associated with a reduced utilization of dietary proteins or with causing other adverse effects. The protein efficiency ratio, biological value and digestibility of this diet did not differ from a corresponding casein diet free from chlorogenic acid. No change was observed in the nitrogen balance of the experimental rats. Neither did the rats show any change in hematological values or volumes and pH of the urine. Some deviation was noticed in the weights of kidneys and adrenals of the chlorogec acid-free casein diet. The findings that were made were normal in the microscopic examinations of various organs. Chlorogenic acid did not seem to influence the ultrastructure of the liver as revealed by electron microscopy."}
{"id": "PMID:5693", "title": "Influence of experimental dietary conditions on hepatic enzymes of glutamic acid metabolism in rats.", "content": "The lowering levels of dietary protein induced a significant fall of some hepatic enzymes associated with glutamic acid metabolism. The changes were later normalised during dietary rehabilitation of the protein-deprived rats. The levels of these enzymes were found to be increased as compared to those observed after starvation, on feeding a carbohydrate-free, protein-rich diet or by the dietary supplementation by glutamic acid.", "contents": "Influence of experimental dietary conditions on hepatic enzymes of glutamic acid metabolism in rats. The lowering levels of dietary protein induced a significant fall of some hepatic enzymes associated with glutamic acid metabolism. The changes were later normalised during dietary rehabilitation of the protein-deprived rats. The levels of these enzymes were found to be increased as compared to those observed after starvation, on feeding a carbohydrate-free, protein-rich diet or by the dietary supplementation by glutamic acid."}
{"id": "PMID:5695", "title": "[Methods of determination of the turnover rate of neuromediators (author's transl)].", "content": "For the study of the effect of a treatment on a neuromediator, the determination of the turnover rate is often more interesting than the determination of the endogenous level of the mediator. Many methods have been used and they are not always isotopic ones. The principal methods are summarized here, especially for catecholamines and serotonin.", "contents": "[Methods of determination of the turnover rate of neuromediators (author's transl)]. For the study of the effect of a treatment on a neuromediator, the determination of the turnover rate is often more interesting than the determination of the endogenous level of the mediator. Many methods have been used and they are not always isotopic ones. The principal methods are summarized here, especially for catecholamines and serotonin."}
{"id": "PMID:5698", "title": "Changes in tyrosine transaminase and phosphoenolpyruvate kinase activities during short term incubation of fetal liver.", "content": "Incubation of fetal rat liver homogenates at 37 degrees for 2-3 hr increased PEPK activity in the 100,000 X g supernatant 5-fold and TTA activity 10-fold. At the same time, activity in the 100,000 X g pellet decreaed and no change was observed in the whole homogenate. It is concluded that during incubation of fetal liver pieces or homogenates in vitro, a redistribution of enzymes occurs between cell particles and cell sap. It is suggested that release of enzyme into the cell sap may be the first stimulus for subsequent enzyme synthesis which occurs after birth.", "contents": "Changes in tyrosine transaminase and phosphoenolpyruvate kinase activities during short term incubation of fetal liver. Incubation of fetal rat liver homogenates at 37 degrees for 2-3 hr increased PEPK activity in the 100,000 X g supernatant 5-fold and TTA activity 10-fold. At the same time, activity in the 100,000 X g pellet decreaed and no change was observed in the whole homogenate. It is concluded that during incubation of fetal liver pieces or homogenates in vitro, a redistribution of enzymes occurs between cell particles and cell sap. It is suggested that release of enzyme into the cell sap may be the first stimulus for subsequent enzyme synthesis which occurs after birth."}
{"id": "PMID:5699", "title": "Oxygen transport in congenital heart disease: influence of fetal hemoglobin, red cell pH, and 2,3-diphosphoglycerate.", "content": "In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2, 3-diphosphoglycerate concentration (RBC 2, 3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO2 and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2, 3-DPG were determined. During the first 50 days of life values of standard P50 (stdP50) (37, pH 7.4), actual in vivo P50 (actP50), RBC 2, 3-DPG, O2 capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP50 and arterial plasma pH and to high values for O2 capacity. After the third month, stdP50 actP50, RBC 2, 3-DPG, O2 capacity, and red cell pH were found to be elevated. Plasma pH and actP50 were scattered around the normal range (Figs. 1 and 2). Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H+ ion and 2, 3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2, 3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2, 3-DPG concentration, indicating that in vivo the 2, 3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin.", "contents": "Oxygen transport in congenital heart disease: influence of fetal hemoglobin, red cell pH, and 2,3-diphosphoglycerate. In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2, 3-diphosphoglycerate concentration (RBC 2, 3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO2 and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2, 3-DPG were determined. During the first 50 days of life values of standard P50 (stdP50) (37, pH 7.4), actual in vivo P50 (actP50), RBC 2, 3-DPG, O2 capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP50 and arterial plasma pH and to high values for O2 capacity. After the third month, stdP50 actP50, RBC 2, 3-DPG, O2 capacity, and red cell pH were found to be elevated. Plasma pH and actP50 were scattered around the normal range (Figs. 1 and 2). Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H+ ion and 2, 3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2, 3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2, 3-DPG concentration, indicating that in vivo the 2, 3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin."}
{"id": "PMID:5701", "title": "Dual effect of 2,3-diphosphoglycerate on the Bohr effects of human blood.", "content": "The influence of the red cell concentration of 2,3-diphosphoglycerate (2,3-DPG, 0.5-26 mumoles/g erythrocytes) on the \"CO2-Bohr effect\" (pH varied by CO2 at constant base excess) and the \"fixed acid-Bohr effect\" (pH varied by fixed acid or base at constant PCO2) was studied in human blood at plasma pH values ranging between pH 7.2 and pH 7.6. Elevation of red cell 2,3-DPG concentration leads to a numerical decrease of the \"CO2-Bohr coefficient\" referring to plasma pH. The \"fixed acid-Bohr coefficients\" are numerically smaller than the corresponding \"CO2-Bohr coefficients\" and exhibit a maximum at normal red cell 2,3-DPG concentrations. The Bohr coefficients referring to red cell pH are distinctly higher than those referring to plasma pH, especially at high 2,3-DPG levels. This is due on the one hand to the physico-chemical properties of the intact red cell membrane, and on the other hand to a 2,3-DPG-induced decrease in the ratio deltapHcell/deltapHplasma. From the results it is concluded that 2,3-DPG exerts a dual effect on the Bohr coefficients of whole blood which is mediated 1. by the direct effect of 2,3-DPG on the allosteric properties of hemoglobin (as reflected by changes of the Bohr coefficients referring to red cell pH), and 2. by the effect of 2,3-DPG on deltapHcell/deltapHplasma.", "contents": "Dual effect of 2,3-diphosphoglycerate on the Bohr effects of human blood. The influence of the red cell concentration of 2,3-diphosphoglycerate (2,3-DPG, 0.5-26 mumoles/g erythrocytes) on the \"CO2-Bohr effect\" (pH varied by CO2 at constant base excess) and the \"fixed acid-Bohr effect\" (pH varied by fixed acid or base at constant PCO2) was studied in human blood at plasma pH values ranging between pH 7.2 and pH 7.6. Elevation of red cell 2,3-DPG concentration leads to a numerical decrease of the \"CO2-Bohr coefficient\" referring to plasma pH. The \"fixed acid-Bohr coefficients\" are numerically smaller than the corresponding \"CO2-Bohr coefficients\" and exhibit a maximum at normal red cell 2,3-DPG concentrations. The Bohr coefficients referring to red cell pH are distinctly higher than those referring to plasma pH, especially at high 2,3-DPG levels. This is due on the one hand to the physico-chemical properties of the intact red cell membrane, and on the other hand to a 2,3-DPG-induced decrease in the ratio deltapHcell/deltapHplasma. From the results it is concluded that 2,3-DPG exerts a dual effect on the Bohr coefficients of whole blood which is mediated 1. by the direct effect of 2,3-DPG on the allosteric properties of hemoglobin (as reflected by changes of the Bohr coefficients referring to red cell pH), and 2. by the effect of 2,3-DPG on deltapHcell/deltapHplasma."}
{"id": "PMID:5702", "title": "Influence of 2,3-diphosphoglycerate on the buffering properties of human blood: role of the red cell membrane.", "content": "The effect of the concentration of red cell 2,3-diphosphoglycerate (2,3-DPG, 0.5-21 mumoles/g cells) on the buffering properties and on the slope of the relation between the extracellular and intracellular pH (deltapHi/deltapHe) of human blood was studied. The results were evaluated in connection with previous findings concerning the effect of 2,3-DPG on the Donnan ratio rH+ = H+e/H+i. deltapHi/deltapHe decreases with rising red cell 2,3-DPG content as well as with rising extracellular pH. deltapHi/deltapHe and rH+ can be related to each other by the empirical equation deltapHi/deltapHe = 1 + log rH+ = 1 + pHi - pHe. The validity of this equation appears to be restricted to conditions where the Donnan ratio rH+ is altered between 0.3 and 1 either by changes of the red cell concentration of buffering anions such as 2,3-DPG or by changes of the extracellular pH. As determined in suspensions of red cells with intact membranes, the 2,3-DPG-and pH-induced changes of deltapHi/deltapHe lead to proportional changes in the buffering power of the non-bicarbonate buffers of erythrocytes. Due to this effect the buffering power of suspensions of cells containing 5 times the normal concentration of the buffer 2,3-DPG is lower than that of cells with normal 2,3-DPG content (at extracellular pH values above 7). These findings demonstrate that the action of intracellular non-bicarbonate buffers in blood is effectively modulated by the physico-chemical properties of the red cell membrane.", "contents": "Influence of 2,3-diphosphoglycerate on the buffering properties of human blood: role of the red cell membrane. The effect of the concentration of red cell 2,3-diphosphoglycerate (2,3-DPG, 0.5-21 mumoles/g cells) on the buffering properties and on the slope of the relation between the extracellular and intracellular pH (deltapHi/deltapHe) of human blood was studied. The results were evaluated in connection with previous findings concerning the effect of 2,3-DPG on the Donnan ratio rH+ = H+e/H+i. deltapHi/deltapHe decreases with rising red cell 2,3-DPG content as well as with rising extracellular pH. deltapHi/deltapHe and rH+ can be related to each other by the empirical equation deltapHi/deltapHe = 1 + log rH+ = 1 + pHi - pHe. The validity of this equation appears to be restricted to conditions where the Donnan ratio rH+ is altered between 0.3 and 1 either by changes of the red cell concentration of buffering anions such as 2,3-DPG or by changes of the extracellular pH. As determined in suspensions of red cells with intact membranes, the 2,3-DPG-and pH-induced changes of deltapHi/deltapHe lead to proportional changes in the buffering power of the non-bicarbonate buffers of erythrocytes. Due to this effect the buffering power of suspensions of cells containing 5 times the normal concentration of the buffer 2,3-DPG is lower than that of cells with normal 2,3-DPG content (at extracellular pH values above 7). These findings demonstrate that the action of intracellular non-bicarbonate buffers in blood is effectively modulated by the physico-chemical properties of the red cell membrane."}
{"id": "PMID:5705", "title": "Conformation and reactivity of DNA in the complex with proteins. III. Helix-coil transition and conformational studies of model complexes of DNA's with poly-L-histidine.", "content": "Differences in the interaction of poly-L-histidine with DNA of various base composition have been demonstrated using melting and CD measurements. The two types of complexes formed with DNA at pH values below the pK of 5.9 and in the region of pH 6.5 are very different in their CD spectral properties. The binding effects with highly protonated poly-L-histidine are AT-dependent as reflected by large negative CD spectra indicating the formation of psi-DNA as a condensed state of the double helix. GC-rich DNA may, however, also form psi-DNA structures with poly-L-histidine under certain conditions. At pH 6.5 complex formation with the weakly protonated polypeptide is GC-dependent. From the results it is concluded that protonated poly-L-histidine interacts more specifically at AT base pairs, prabably along the small groove while the weakly protonated poly-L-histidine tends to interact preferentially with GC regions which seems to occur rather in the large groove.", "contents": "Conformation and reactivity of DNA in the complex with proteins. III. Helix-coil transition and conformational studies of model complexes of DNA's with poly-L-histidine. Differences in the interaction of poly-L-histidine with DNA of various base composition have been demonstrated using melting and CD measurements. The two types of complexes formed with DNA at pH values below the pK of 5.9 and in the region of pH 6.5 are very different in their CD spectral properties. The binding effects with highly protonated poly-L-histidine are AT-dependent as reflected by large negative CD spectra indicating the formation of psi-DNA as a condensed state of the double helix. GC-rich DNA may, however, also form psi-DNA structures with poly-L-histidine under certain conditions. At pH 6.5 complex formation with the weakly protonated polypeptide is GC-dependent. From the results it is concluded that protonated poly-L-histidine interacts more specifically at AT base pairs, prabably along the small groove while the weakly protonated poly-L-histidine tends to interact preferentially with GC regions which seems to occur rather in the large groove."}
{"id": "PMID:5706", "title": "Conformation and reactivity of DNA in the complex with protein. IV. Circular dichroism of poly-L-histidine model complexes with DNA polymers and specificity of the interaction.", "content": "The CD study of the DNA-poly-L-histidine complex at high degree of protonation revealed that complex formation is already observable at 2 M NaCl. The influence of salt together with 5 M urea suggests that in addition to electrostatic interactions probably hydrogen bonding may favour specific complexes. Affinity of protonated histidines to AT-rich regions is strongly supported by the complexes formed with (dA.dT)-containing polymers. The psi-type structure occurs with poly(dA-dT)-poly(dA-dT) while poly(dA)-poly(dT) is restricted to form a similar psi-state on interaction with highly protonated poly-L-histidine. Differences in the helix winding properties due to variation in the sequence is suggested as a possible factor in the formation of the psi-type complexes. The mechanism of interaction including hydrogen bonding of histidine side-chains with an AT pair at high degree of protonation and with GC-regions at lower degree of protonation in the polypeptide structure is discussed.", "contents": "Conformation and reactivity of DNA in the complex with protein. IV. Circular dichroism of poly-L-histidine model complexes with DNA polymers and specificity of the interaction. The CD study of the DNA-poly-L-histidine complex at high degree of protonation revealed that complex formation is already observable at 2 M NaCl. The influence of salt together with 5 M urea suggests that in addition to electrostatic interactions probably hydrogen bonding may favour specific complexes. Affinity of protonated histidines to AT-rich regions is strongly supported by the complexes formed with (dA.dT)-containing polymers. The psi-type structure occurs with poly(dA-dT)-poly(dA-dT) while poly(dA)-poly(dT) is restricted to form a similar psi-state on interaction with highly protonated poly-L-histidine. Differences in the helix winding properties due to variation in the sequence is suggested as a possible factor in the formation of the psi-type complexes. The mechanism of interaction including hydrogen bonding of histidine side-chains with an AT pair at high degree of protonation and with GC-regions at lower degree of protonation in the polypeptide structure is discussed."}
{"id": "PMID:5707", "title": "Effect of excision of the Y-base on the interaction of tRNAPhe (yeast) with phenylalanyl-tRNA synthetase (yeast).", "content": "The interaction between tRNAPhe (yeast), from which the Y-base has been removed by acid treatment, and phenylalanyl-tRNA synthetase (yeast) has been investigated by fluorescence competition titrations and sedimentation velocity runs. The binding parameters are given under various ionic conditions. The tRNAPhe-Y still can occupy the specific binding sites on the enzyme. Compared to unmodified tRNAPhe, the binding constant is lowered by more than one order of magnitude. It can be concluded that the Y-base is not necessary for specific recognition of tRNAPhe by the cognate synthetase, it rather may represent a point of attachment for the synthetase.", "contents": "Effect of excision of the Y-base on the interaction of tRNAPhe (yeast) with phenylalanyl-tRNA synthetase (yeast). The interaction between tRNAPhe (yeast), from which the Y-base has been removed by acid treatment, and phenylalanyl-tRNA synthetase (yeast) has been investigated by fluorescence competition titrations and sedimentation velocity runs. The binding parameters are given under various ionic conditions. The tRNAPhe-Y still can occupy the specific binding sites on the enzyme. Compared to unmodified tRNAPhe, the binding constant is lowered by more than one order of magnitude. It can be concluded that the Y-base is not necessary for specific recognition of tRNAPhe by the cognate synthetase, it rather may represent a point of attachment for the synthetase."}
{"id": "PMID:5708", "title": "Distribution of histones in alkali-denatured chromatin studied by isopycnic centrifugation in alkaline metrizamide density gradients.", "content": "Three types of density gradients - neutral metrizamide, alkaline NaOH-metrizamide and alkaline triethanolamine-metrizamide - were used for studying the distribution of histones between the two DNA strands in alkali-denatured chromatin. It was found possible to avoid both protein redistribution and dissociation by using triethanolamine-metrizamide density gradients at pH 10.5. Under these conditions an alkali-denatured mixture of DNA and chromatin was well separated into the original DNA and DNP. When native or sonicated chromatin was denatured at pH 12.2 and centrifuged in a triethanolamine-metrizamide density gradient at pH 10.5 no peak of free DNA appeared. These results show that both DNA strands remain associated with histone molecules upon alkaline denaturation of chromatin.", "contents": "Distribution of histones in alkali-denatured chromatin studied by isopycnic centrifugation in alkaline metrizamide density gradients. Three types of density gradients - neutral metrizamide, alkaline NaOH-metrizamide and alkaline triethanolamine-metrizamide - were used for studying the distribution of histones between the two DNA strands in alkali-denatured chromatin. It was found possible to avoid both protein redistribution and dissociation by using triethanolamine-metrizamide density gradients at pH 10.5. Under these conditions an alkali-denatured mixture of DNA and chromatin was well separated into the original DNA and DNP. When native or sonicated chromatin was denatured at pH 12.2 and centrifuged in a triethanolamine-metrizamide density gradient at pH 10.5 no peak of free DNA appeared. These results show that both DNA strands remain associated with histone molecules upon alkaline denaturation of chromatin."}
{"id": "PMID:5709", "title": "Pyrimidine nucleoside analogues.X. 5-Substituted 1-(1,3-dihydroxypropyl-2) uracils.", "content": "A convenient method is suggested for synthesis of uracil-1-malonic acid diethyl ester by alkylating 2,4-bis(trimethylsilyl) uracil with bromo-malonic acid diethyl ester. This compound has been shown to hydrolyze with NaOH yielding either uracil or uracil-1-acetic acid, depending on reaction conditions. Similarly, thymine-1-malinic acid diethyl ester and 5-fluorouracil-1,3-dimalonic acid tetraethyl ester were obtained. 1-(1,3-Dihydroxypropyl)uracil has been obtained by reducing uracil-1-malonic acid diethyl ester with NaBH4.", "contents": "Pyrimidine nucleoside analogues.X. 5-Substituted 1-(1,3-dihydroxypropyl-2) uracils. A convenient method is suggested for synthesis of uracil-1-malonic acid diethyl ester by alkylating 2,4-bis(trimethylsilyl) uracil with bromo-malonic acid diethyl ester. This compound has been shown to hydrolyze with NaOH yielding either uracil or uracil-1-acetic acid, depending on reaction conditions. Similarly, thymine-1-malinic acid diethyl ester and 5-fluorouracil-1,3-dimalonic acid tetraethyl ester were obtained. 1-(1,3-Dihydroxypropyl)uracil has been obtained by reducing uracil-1-malonic acid diethyl ester with NaBH4."}
{"id": "PMID:5710", "title": "Preparation and properties of poly 2'-O-ethylcytidylic acid.", "content": "Poly 2'0-ethylcytidylic acid (poly (Ce)) was prepared by polymerization of 2'-0-ethylcytidine-5'-pyrophosphate with Escherichia coli polynucleotide phosphorylase in the presence of Mn++, and its properties compared with those of poly (rC), poly (Cm) and poly (dC). The neutral form of pOLY (Ce) exhibits properties similar to those of poly (rC) and poly (Cm). It also forms an acid twin-stranded helix with a transition pH of 5.9 in 0.1 M NaCl. The neutral form readily forms a double-stranded helical complex with poly (rI). Relative to poly (Cm), replacement of the 2'-0-methyl by 2-0-ethyl leads to increased enhancement of the thermal stabilities of both the acid helical form of poly (Ce) and its complex with poly (rI).", "contents": "Preparation and properties of poly 2'-O-ethylcytidylic acid. Poly 2'0-ethylcytidylic acid (poly (Ce)) was prepared by polymerization of 2'-0-ethylcytidine-5'-pyrophosphate with Escherichia coli polynucleotide phosphorylase in the presence of Mn++, and its properties compared with those of poly (rC), poly (Cm) and poly (dC). The neutral form of pOLY (Ce) exhibits properties similar to those of poly (rC) and poly (Cm). It also forms an acid twin-stranded helix with a transition pH of 5.9 in 0.1 M NaCl. The neutral form readily forms a double-stranded helical complex with poly (rI). Relative to poly (Cm), replacement of the 2'-0-methyl by 2-0-ethyl leads to increased enhancement of the thermal stabilities of both the acid helical form of poly (Ce) and its complex with poly (rI)."}
{"id": "PMID:5711", "title": "O2'-Methylinosine, a constituent of the ribosomal RNA of Crithidia fasciculata.", "content": "A novel nucleoside, O2'-methylinosine (Im), has been identified as a constituent of the ribosomal RNA of Crithidia fasciculata, a hemoflaggelate protozoan. The nucleoside is released as part of an alkali-stable dinucleotide, Im-Up, by alkaline hydrolysis of Crithidia rRNA, and as a 5'-nucleotide, pIm, by snake venom hydrolysis of the same RNA. The Im-containing derivatives isolated from Crithidia rRNA were characterized by comparison with marker compounds prepared by chemical deamination of the corresponding adenosine analogues. O2'-Methylinosine prepared from either natural Im-Up or natural pIm had the same ultraviolet absorption spectra and chromatographic properties as marker Im. Characterization of the base and sugar components of Im as hypoxanthine and 2-O-methylribose, respectively, provided final confimration of structure. Control experiments have eliminated the possibility that Im arises from O2'-methyladenosine (Am), a known constituent of ribosomal RNA, by chemical or enzymatic deamination during hydrolysis of Crithidia rRNA.", "contents": "O2'-Methylinosine, a constituent of the ribosomal RNA of Crithidia fasciculata. A novel nucleoside, O2'-methylinosine (Im), has been identified as a constituent of the ribosomal RNA of Crithidia fasciculata, a hemoflaggelate protozoan. The nucleoside is released as part of an alkali-stable dinucleotide, Im-Up, by alkaline hydrolysis of Crithidia rRNA, and as a 5'-nucleotide, pIm, by snake venom hydrolysis of the same RNA. The Im-containing derivatives isolated from Crithidia rRNA were characterized by comparison with marker compounds prepared by chemical deamination of the corresponding adenosine analogues. O2'-Methylinosine prepared from either natural Im-Up or natural pIm had the same ultraviolet absorption spectra and chromatographic properties as marker Im. Characterization of the base and sugar components of Im as hypoxanthine and 2-O-methylribose, respectively, provided final confimration of structure. Control experiments have eliminated the possibility that Im arises from O2'-methyladenosine (Am), a known constituent of ribosomal RNA, by chemical or enzymatic deamination during hydrolysis of Crithidia rRNA."}
{"id": "PMID:5720", "title": "Observations and interpretation of x-ray absorption edges in iron compounds and proteins.", "content": "X-ray absorption spectra near the Kalpha edge have been measured in various iron group compounds using the intense synchrotron radiation at the Stanford Synchrotron Research Project. In the cubic compounds KMF3 where M = Mn+2, Fe+2, Co+2, Ni+2, and Zn+2, well resolved lines were observed and assigned to the 1s leads to 3d, 1s leads to 4s, and 1s leads to 4p transitions. The observed energies agreed rather well with the spectroscopic energy levels of the Z + 1 ion and the intensities are shown to agree with those expected on the basis of one electron transitions of the form Z 1s2dn(L,S) leads to (Z + 1)1s2dnn'l'(L\",S). The energies of the intense 1s leads to 4p transition increase by about 5 V going from KFeF3 to K2NaFeF6, but only by about 1 V from K4Fe(CN)6 to K3Fe(CN)6. The transitions confirm that upon oxidation of the hexacyanides the iron electronic structure barely changes. In the iron sulfur protein rubredoxin, where the iron is bound to a tetrahedron of sulfurs, the 1s leads to 3d transition was about seven times more intense than the same transition in an octahedrally coordinated compound. These intensities parallel those observed in the d-d transitions of optical spectra, because in both types of spectra the intensities depend upon 4p admixture. In the heme protein cytochrome c, upon oxidation the 1s leads to 4p transition shifts only about 1 V to higher energies similar to the iron hexacyanides. These results are discussed in terms of covalent bonding.", "contents": "Observations and interpretation of x-ray absorption edges in iron compounds and proteins. X-ray absorption spectra near the Kalpha edge have been measured in various iron group compounds using the intense synchrotron radiation at the Stanford Synchrotron Research Project. In the cubic compounds KMF3 where M = Mn+2, Fe+2, Co+2, Ni+2, and Zn+2, well resolved lines were observed and assigned to the 1s leads to 3d, 1s leads to 4s, and 1s leads to 4p transitions. The observed energies agreed rather well with the spectroscopic energy levels of the Z + 1 ion and the intensities are shown to agree with those expected on the basis of one electron transitions of the form Z 1s2dn(L,S) leads to (Z + 1)1s2dnn'l'(L\",S). The energies of the intense 1s leads to 4p transition increase by about 5 V going from KFeF3 to K2NaFeF6, but only by about 1 V from K4Fe(CN)6 to K3Fe(CN)6. The transitions confirm that upon oxidation of the hexacyanides the iron electronic structure barely changes. In the iron sulfur protein rubredoxin, where the iron is bound to a tetrahedron of sulfurs, the 1s leads to 3d transition was about seven times more intense than the same transition in an octahedrally coordinated compound. These intensities parallel those observed in the d-d transitions of optical spectra, because in both types of spectra the intensities depend upon 4p admixture. In the heme protein cytochrome c, upon oxidation the 1s leads to 4p transition shifts only about 1 V to higher energies similar to the iron hexacyanides. These results are discussed in terms of covalent bonding."}
{"id": "PMID:5721", "title": "Nuclear magnetic resonance studies of slowly exchanging peptide protons in cytochrome c in aqueous solution.", "content": "The slowly exchanging protons in oxidized and reduced horse heart cytochrome c (D20, uncorrected pH meter reading 6.5 room temperature) have been monitored by recording the 270 and 360 MHz proton nuclear magnetic resonance spectra of the reduced protein between 5 and 11 parts per million downfield from 2,2-dimethyl-2-silapentane-5-sulfonate.", "contents": "Nuclear magnetic resonance studies of slowly exchanging peptide protons in cytochrome c in aqueous solution. The slowly exchanging protons in oxidized and reduced horse heart cytochrome c (D20, uncorrected pH meter reading 6.5 room temperature) have been monitored by recording the 270 and 360 MHz proton nuclear magnetic resonance spectra of the reduced protein between 5 and 11 parts per million downfield from 2,2-dimethyl-2-silapentane-5-sulfonate."}
{"id": "PMID:5722", "title": "15N nuclear magnetic resonance investigations on amino acids.", "content": "15N nuclear magnetic resonance investigations of some amino acids were carried out in order to check the applicability of this method to biological problems. Because the natural abundance of the 15N isotope is not sufficient to get readable spectra in a reasonable time, 95% 15N isotope-enriched samples were used for the measurements. Besides the chemical shift values, the line widths, and the nuclear Overhauser enhancement factors, spin lattice relaxation times of the correspondent 15N resonances were measured as functions of pH had temperature.", "contents": "15N nuclear magnetic resonance investigations on amino acids. 15N nuclear magnetic resonance investigations of some amino acids were carried out in order to check the applicability of this method to biological problems. Because the natural abundance of the 15N isotope is not sufficient to get readable spectra in a reasonable time, 95% 15N isotope-enriched samples were used for the measurements. Besides the chemical shift values, the line widths, and the nuclear Overhauser enhancement factors, spin lattice relaxation times of the correspondent 15N resonances were measured as functions of pH had temperature."}
{"id": "PMID:5723", "title": "Desensitization of beta-adrenergic receptors by beta-adrenergic agonists in a cell-free system: resensitization by guanosine 5'-(beta, gamma-imino)triphosphate and other purine nucleotides.", "content": "Incubation of purified frog erythrocyte membranes with beta-adrenergic agonists at 25 degrees produces relatively rapid (half-time about 10 min) desensitization (inactivation) of about 60% of the beta-adrenergic receptor binding sites. The desensitized receptors no longer bind the specific beta-adrenergic ligand (-)[3H]dihydroalprenolol. The decrease in the number of functional beta-adrenergic receptors is also manifest as a decreased ability of isoproterenol to stimulate the membrane-bound adenylate cyclase.", "contents": "Desensitization of beta-adrenergic receptors by beta-adrenergic agonists in a cell-free system: resensitization by guanosine 5'-(beta, gamma-imino)triphosphate and other purine nucleotides. Incubation of purified frog erythrocyte membranes with beta-adrenergic agonists at 25 degrees produces relatively rapid (half-time about 10 min) desensitization (inactivation) of about 60% of the beta-adrenergic receptor binding sites. The desensitized receptors no longer bind the specific beta-adrenergic ligand (-)[3H]dihydroalprenolol. The decrease in the number of functional beta-adrenergic receptors is also manifest as a decreased ability of isoproterenol to stimulate the membrane-bound adenylate cyclase."}
{"id": "PMID:5724", "title": "An assay of ribonuclease H, endoribonucleases, and phosphatases.", "content": "An assay for ribonuclease H (EC 3.1.4.34) is described which permits the estimation of the number and the type of cleavages produced by the enzyme when acting on the ribo moiety of a DNA-RNA hybrid substrate. With six different homopolymer hybrids tested, the number of enzymically induced breaks varied widely. The method is applicable to other endoribonucleases, phosphodiesterases, and phosphatases.", "contents": "An assay of ribonuclease H, endoribonucleases, and phosphatases. An assay for ribonuclease H (EC 3.1.4.34) is described which permits the estimation of the number and the type of cleavages produced by the enzyme when acting on the ribo moiety of a DNA-RNA hybrid substrate. With six different homopolymer hybrids tested, the number of enzymically induced breaks varied widely. The method is applicable to other endoribonucleases, phosphodiesterases, and phosphatases."}
{"id": "PMID:5725", "title": "Bacteriophage T5-induced endonucleases that introduce site-specific single-chain interruptions in duplex DNA.", "content": "Four site-specific endodeoxyribonucleases have been partially purified from extracts of bacteriophage T5-infected Escherichia coli by gel filtration and affinity chromatography on single- and double-stranded DNA. The enzymes were detected and characterized by agarose gel electrophoresis of alkali-denatured digestion products. None of the four is found in uninfected cells. In the presence of a divalent cation, all four endonucleases make ligase-repairable, single-chain interruptions at specific sites in the duplex DNA of several bacteriophages (lambda, T7, and T5) and a mammalian virus (adenovirus 2). These activities are not stimulated by ATP. None of the four is active on single-stranded DNA. The fragments produced by each enzyme from ligase-repaired T5 DNA do not correspond to those derived from mature T5 DNA. Each of the enzymes is able to cleave the intact strand of T5 DNA.", "contents": "Bacteriophage T5-induced endonucleases that introduce site-specific single-chain interruptions in duplex DNA. Four site-specific endodeoxyribonucleases have been partially purified from extracts of bacteriophage T5-infected Escherichia coli by gel filtration and affinity chromatography on single- and double-stranded DNA. The enzymes were detected and characterized by agarose gel electrophoresis of alkali-denatured digestion products. None of the four is found in uninfected cells. In the presence of a divalent cation, all four endonucleases make ligase-repairable, single-chain interruptions at specific sites in the duplex DNA of several bacteriophages (lambda, T7, and T5) and a mammalian virus (adenovirus 2). These activities are not stimulated by ATP. None of the four is active on single-stranded DNA. The fragments produced by each enzyme from ligase-repaired T5 DNA do not correspond to those derived from mature T5 DNA. Each of the enzymes is able to cleave the intact strand of T5 DNA."}
{"id": "PMID:5726", "title": "Regulation of guanylate and adenylate cyclase activities by lysolecithin.", "content": "The guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] in membrane preparations from 3T3 mouse fibroblasts is stimulated approximately 5-fold by lysolecithin at concentrations of 100 mug/ml and above.", "contents": "Regulation of guanylate and adenylate cyclase activities by lysolecithin. The guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] in membrane preparations from 3T3 mouse fibroblasts is stimulated approximately 5-fold by lysolecithin at concentrations of 100 mug/ml and above."}
{"id": "PMID:5727", "title": "Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation.", "content": "Mice with the X-chromosomal sparse-fur (spf) mutation frequently have urinary bladder stones composed mostly of orotic acid, which was identified by the following criteria: ultraviolet and infrared absorption, spectra, chromatographic behavior, melting point, and reactivity in a specific color test. This clue led to the discovery that spf-bearing mice have an abnormal form of liver ornithine carbamoyltransferase (carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3). Normal ornithine carbamoyltransferase has maximum activity at pH 7.6-8.0 and 80% of maximum activity at pH 10.0.", "contents": "Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation. Mice with the X-chromosomal sparse-fur (spf) mutation frequently have urinary bladder stones composed mostly of orotic acid, which was identified by the following criteria: ultraviolet and infrared absorption, spectra, chromatographic behavior, melting point, and reactivity in a specific color test. This clue led to the discovery that spf-bearing mice have an abnormal form of liver ornithine carbamoyltransferase (carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3). Normal ornithine carbamoyltransferase has maximum activity at pH 7.6-8.0 and 80% of maximum activity at pH 10.0."}
{"id": "PMID:5737", "title": "The structure and function of thoracic exopodites in the larvae of the lobster Homarus gammarus (L.).", "content": "The first three larval stages of the lobster Homarus gammarus are pelagic swimming animals. A description is given of the exopodite apparatus of the thoracic appendages that provide lift and propulsive power in these stages. Setal arrangement and display provides greater surface area during power strokes. Musculature is peculiar to the exopodites and concerned with rotational movements of the appendage. Metachronal beating takes place with the segmental appendages moving in a variable sequence.", "contents": "The structure and function of thoracic exopodites in the larvae of the lobster Homarus gammarus (L.). The first three larval stages of the lobster Homarus gammarus are pelagic swimming animals. A description is given of the exopodite apparatus of the thoracic appendages that provide lift and propulsive power in these stages. Setal arrangement and display provides greater surface area during power strokes. Musculature is peculiar to the exopodites and concerned with rotational movements of the appendage. Metachronal beating takes place with the segmental appendages moving in a variable sequence."}
{"id": "PMID:5738", "title": "A quantitative analysis of exopodite beating in the larvae of the lobster Homarus gammarus (L.).", "content": "Raw data on exopodite beating in the first three developmental stages of the lobster Homarus gammarus were collected and analysed for key beating parameters. The analysis was computer assisted and the main procedures used are described. Beating patterns are the same in all three stages and are usually very regular although perturbations do occur (figures 1, 2). When beating stops the deceleration and subsequent re-acceleration is very rapid (figure 1) and limb movement sequences usually start posteriorly and move forwards (figures 1, 2d). Ipsilateral phase relations are generally maintained at 0.4-0.6 (figures, 3,4) and while the coupling between adjacent exopodites is usually stronger than for those further apart various deviations from this are occasionally seen (figure 5). No significant correlation between the ipsilateral phase relations of adjacent exopodites and base cycle duration was detected for any of the stages (figure 6). Contralateral phase relations undergo a constant progression (figures 7, 9) and this was found to be due to a heterodyne effect (figure 8) also described as gliding coordination. The powerstroke/returnstroke ratio for all stages was approximately 0.5 (figure 10) and no significant correlation was found with cycle duration (figure 11). The only substantial difference between the three larval stages which was noted was that of cycle duration, the cycles of stage III being shorter than those of the first two stages. The exopodite beating pattern was discussed in context with other metachronously cycling systems in arthropods and the implications of the present study discussed.", "contents": "A quantitative analysis of exopodite beating in the larvae of the lobster Homarus gammarus (L.). Raw data on exopodite beating in the first three developmental stages of the lobster Homarus gammarus were collected and analysed for key beating parameters. The analysis was computer assisted and the main procedures used are described. Beating patterns are the same in all three stages and are usually very regular although perturbations do occur (figures 1, 2). When beating stops the deceleration and subsequent re-acceleration is very rapid (figure 1) and limb movement sequences usually start posteriorly and move forwards (figures 1, 2d). Ipsilateral phase relations are generally maintained at 0.4-0.6 (figures, 3,4) and while the coupling between adjacent exopodites is usually stronger than for those further apart various deviations from this are occasionally seen (figure 5). No significant correlation between the ipsilateral phase relations of adjacent exopodites and base cycle duration was detected for any of the stages (figure 6). Contralateral phase relations undergo a constant progression (figures 7, 9) and this was found to be due to a heterodyne effect (figure 8) also described as gliding coordination. The powerstroke/returnstroke ratio for all stages was approximately 0.5 (figure 10) and no significant correlation was found with cycle duration (figure 11). The only substantial difference between the three larval stages which was noted was that of cycle duration, the cycles of stage III being shorter than those of the first two stages. The exopodite beating pattern was discussed in context with other metachronously cycling systems in arthropods and the implications of the present study discussed."}
{"id": "PMID:5739", "title": "A comparison of beating parameters in larval and post-larval locomotor systems of the lobster Homarus gammarus (L.).", "content": "A study has been made of the interrelations between rhythmical exopodite beating in different larval stages and swimmeret beating in poast-larval stages of the lobster Homarus gammarus. Data on exopodite beat cycle durations have been used for statistical comparisons of exopodite performance within one larva, and also between different stages of larval development. Inter-exopodite comparisons reveal clear bilateral differences (table 1), although there is no consistently favoured relationship (tables 2 and 3). There are significant differences in cycle duration between the first three developmental stages, with a slight increase at the first moult, and a marked decrease at the second (table 4). However, within each stage the repeat frequency exhibits little change (table 5). Therefore it appears that changes in swimming behaviour occur discontinuously in development, and are associated with the larval moults. It is suggested that changes in beat frequency, and especially the faster beating in stage III, may represent responses to changed loading conditions (table 7). Measurements of swimmeret beating in post-larval lobsters have been analysed in terms of cycle durations, and inter- and intra-segmental phase relations. Swimmeret beating patterns are very regular (figure 1), but not restricted to a narrow range of frequencies (table 6a). Intersegmental phase lag remains constant around 0.2 (figure 3) independent of beat frequency (figure 4). Similarly the powerstroke/returnstroke ratio of approximately 0.5 (figure 5) shows no significant correlation with cycle duration (figure 6). Differences emerge in the performance of larval exopodites and post-larval swimmerets (table 6b), although the possibility cannot be excluded that the larval exopodite oscillator in some way influences the developing action of the post-larval swimmeret system.", "contents": "A comparison of beating parameters in larval and post-larval locomotor systems of the lobster Homarus gammarus (L.). A study has been made of the interrelations between rhythmical exopodite beating in different larval stages and swimmeret beating in poast-larval stages of the lobster Homarus gammarus. Data on exopodite beat cycle durations have been used for statistical comparisons of exopodite performance within one larva, and also between different stages of larval development. Inter-exopodite comparisons reveal clear bilateral differences (table 1), although there is no consistently favoured relationship (tables 2 and 3). There are significant differences in cycle duration between the first three developmental stages, with a slight increase at the first moult, and a marked decrease at the second (table 4). However, within each stage the repeat frequency exhibits little change (table 5). Therefore it appears that changes in swimming behaviour occur discontinuously in development, and are associated with the larval moults. It is suggested that changes in beat frequency, and especially the faster beating in stage III, may represent responses to changed loading conditions (table 7). Measurements of swimmeret beating in post-larval lobsters have been analysed in terms of cycle durations, and inter- and intra-segmental phase relations. Swimmeret beating patterns are very regular (figure 1), but not restricted to a narrow range of frequencies (table 6a). Intersegmental phase lag remains constant around 0.2 (figure 3) independent of beat frequency (figure 4). Similarly the powerstroke/returnstroke ratio of approximately 0.5 (figure 5) shows no significant correlation with cycle duration (figure 6). Differences emerge in the performance of larval exopodites and post-larval swimmerets (table 6b), although the possibility cannot be excluded that the larval exopodite oscillator in some way influences the developing action of the post-larval swimmeret system."}
{"id": "PMID:5740", "title": "The nervous system of Loligo. II. Suboesophageal centres.", "content": "A well-marked hierarchy of centres can be recognized within the suboesophageal lobes and ganglia of the arms. The inputs and outputs of each lobe are described. There are sets of motoneurons and intermediate motor centres, which can be activated either from the periphery or from above. They mostly do not send fibres up to the optic or higher motor centres. However, there is a large set of fibres running from the magnocellular lobe to all the basal supraoesophageal lobes. The centre for control of the four eye-muscle nerves in the anterior lateral pedal lobe receives many fibres direct from the statocyst and from the peduncle and basal lobes, but none direct from the optic lobe. The posterior lateral pedal is a backward continuation of the oculomotor centre, containing large cells that may be concerned in initiating attacks by the tentacles. An intermediate motor centre in the posterior pedal lobe probably controls steering. It sends fibres to the funned and head retractors, and by both direct and interrupted pathways to the fin lobe. It receives fibres from the crista nerve and basal lobes, but none direct from the optic lobe. The jet control centre of the ventral magnocellular lobe receives fibres from the statocyst and skin and also from the optic and basal lobes. Some of these last also give extensive branches throughout the palliovisceral lobes. The branching patterns of the dendritic collaterals differ in the various lobes. Some estimates are given of the numbers of synaptic points. The dendritic collaterals of the motoneurons spread through large volumes of neuropil and they overlap. The incoming fibres spread widely and each presumably activates many motoneurons either together or serially. Many of the lobes contain numerous microneurons with short trunks restricted to the lobe, but there are none of these cells in the chromatophore lobes or fin lobes. The microneurons have only few dendritic collaterals, in contrast to the numerous ones on the nearby motoneurons.", "contents": "The nervous system of Loligo. II. Suboesophageal centres. A well-marked hierarchy of centres can be recognized within the suboesophageal lobes and ganglia of the arms. The inputs and outputs of each lobe are described. There are sets of motoneurons and intermediate motor centres, which can be activated either from the periphery or from above. They mostly do not send fibres up to the optic or higher motor centres. However, there is a large set of fibres running from the magnocellular lobe to all the basal supraoesophageal lobes. The centre for control of the four eye-muscle nerves in the anterior lateral pedal lobe receives many fibres direct from the statocyst and from the peduncle and basal lobes, but none direct from the optic lobe. The posterior lateral pedal is a backward continuation of the oculomotor centre, containing large cells that may be concerned in initiating attacks by the tentacles. An intermediate motor centre in the posterior pedal lobe probably controls steering. It sends fibres to the funned and head retractors, and by both direct and interrupted pathways to the fin lobe. It receives fibres from the crista nerve and basal lobes, but none direct from the optic lobe. The jet control centre of the ventral magnocellular lobe receives fibres from the statocyst and skin and also from the optic and basal lobes. Some of these last also give extensive branches throughout the palliovisceral lobes. The branching patterns of the dendritic collaterals differ in the various lobes. Some estimates are given of the numbers of synaptic points. The dendritic collaterals of the motoneurons spread through large volumes of neuropil and they overlap. The incoming fibres spread widely and each presumably activates many motoneurons either together or serially. Many of the lobes contain numerous microneurons with short trunks restricted to the lobe, but there are none of these cells in the chromatophore lobes or fin lobes. The microneurons have only few dendritic collaterals, in contrast to the numerous ones on the nearby motoneurons."}
{"id": "PMID:5741", "title": "Psychoactive drugs. Uses, misuses, and abuses.", "content": "The source of knowledge about the use of psychoactive drugs is often biased--being the representative or literature of the pharmaceutical company. Psychotropic drugs and their appropriate usage are discussed, and the basic ingredients of good prescribing habits are examined by focusing on the nonchemical factors that can help determine outcome.", "contents": "Psychoactive drugs. Uses, misuses, and abuses. The source of knowledge about the use of psychoactive drugs is often biased--being the representative or literature of the pharmaceutical company. Psychotropic drugs and their appropriate usage are discussed, and the basic ingredients of good prescribing habits are examined by focusing on the nonchemical factors that can help determine outcome."}
{"id": "PMID:5742", "title": "Understanding acid-base disturbances.", "content": "The physiologic principles of blood pH, Pco2, and bicarbonate homeostasis provide a suitable basis for a systematic approach to the interpretation of acid-base disturbances. Pathogenesis, diagnosis, and management of the four classic acid-base disorders follows.", "contents": "Understanding acid-base disturbances. The physiologic principles of blood pH, Pco2, and bicarbonate homeostasis provide a suitable basis for a systematic approach to the interpretation of acid-base disturbances. Pathogenesis, diagnosis, and management of the four classic acid-base disorders follows."}
{"id": "PMID:5743", "title": "Dystonic reactions following neuroleptics: time course and proposed mechanisms.", "content": "The occurrence of acute dystonic reactions was studied relative to drug pharmacokinetic parameters following a single dose of the phenothiazine, butaperazine. Dystonias occurred more than one half-life from peak butaperazine levels, 23 to 56 h after drug administration. The authors postulate that the appearance of dystonias on falling plasma concentrations may be due to disruption of dopaminergic-cholinergic balance caused by differential antidopaminergic and anticholinergic potencies of the drug.", "contents": "Dystonic reactions following neuroleptics: time course and proposed mechanisms. The occurrence of acute dystonic reactions was studied relative to drug pharmacokinetic parameters following a single dose of the phenothiazine, butaperazine. Dystonias occurred more than one half-life from peak butaperazine levels, 23 to 56 h after drug administration. The authors postulate that the appearance of dystonias on falling plasma concentrations may be due to disruption of dopaminergic-cholinergic balance caused by differential antidopaminergic and anticholinergic potencies of the drug."}
{"id": "PMID:5753", "title": "Lysosomal and neutral hydrolase activity during the regression of cardiac hypertrophy.", "content": "Cardiac hypertrophy was produced in rats by constriction of the ascending aorta. Removal of the constricting band 10 days after operation resulted in rapid decline in left ventricular (LV) weight and total ventricular RNA. Activities of acid RNase and beta-glucuronidase were elevated 3 days after aortic constriction. Activities of cathepsin D and alkaline RNase were unchanges. Activities of cathepsin  D and acid RNase were unchanged 1 and 3 days after removal of constricting band. Ca2+-activated, neutral protease (CAF) isolated from postmitochondrial muscle supernatant was partially purified and characterized. CAF specifically degrades alpha-actinin when incubated with isolated myofibriles in the presence of Ca2+.", "contents": "Lysosomal and neutral hydrolase activity during the regression of cardiac hypertrophy. Cardiac hypertrophy was produced in rats by constriction of the ascending aorta. Removal of the constricting band 10 days after operation resulted in rapid decline in left ventricular (LV) weight and total ventricular RNA. Activities of acid RNase and beta-glucuronidase were elevated 3 days after aortic constriction. Activities of cathepsin D and alkaline RNase were unchanges. Activities of cathepsin  D and acid RNase were unchanged 1 and 3 days after removal of constricting band. Ca2+-activated, neutral protease (CAF) isolated from postmitochondrial muscle supernatant was partially purified and characterized. CAF specifically degrades alpha-actinin when incubated with isolated myofibriles in the presence of Ca2+."}
{"id": "PMID:5754", "title": "Reduced myocardial ATP and creatine phosphate in diabetes: role of 2,3-diphosphoglycerate.", "content": "Observations are presented which suggest that myocardial cellular hypoxia may account for the reduction in myocardial ATP and CP in the ketoacidotic diabetic state. It is suggested that reduced 2,3-diphosphoglycerate adversely affects oxygen release from the red blood cell, thereby leading to myocardial cellular hypoxia.", "contents": "Reduced myocardial ATP and creatine phosphate in diabetes: role of 2,3-diphosphoglycerate. Observations are presented which suggest that myocardial cellular hypoxia may account for the reduction in myocardial ATP and CP in the ketoacidotic diabetic state. It is suggested that reduced 2,3-diphosphoglycerate adversely affects oxygen release from the red blood cell, thereby leading to myocardial cellular hypoxia."}
{"id": "PMID:5755", "title": "Early changes in myocardial hypoxia: relations among mechanical function, pH, and intracellular redox states.", "content": "When rat hearts were subjected to abrupt hypoxia the onset of NADH changes as measured by epicardial fluorescence and of depressed contractility occurred at similar times. Direct measurements of changes in tissue metabolism lagged behind changes in fluorescence and contractility. Calculated NAD:NADH ratios became reduced more rapidly and to a greater extent in the cytoplasm than in the mitochondria, but did not necessarily signal greater changes in total NADH. The detection of depressed contractility before a fall in intracellular pH or a rise in intracellular lactate casts doubt on the postulate that an increase in hydrogen ion is the primary cause of hypoxic myocardial failure.", "contents": "Early changes in myocardial hypoxia: relations among mechanical function, pH, and intracellular redox states. When rat hearts were subjected to abrupt hypoxia the onset of NADH changes as measured by epicardial fluorescence and of depressed contractility occurred at similar times. Direct measurements of changes in tissue metabolism lagged behind changes in fluorescence and contractility. Calculated NAD:NADH ratios became reduced more rapidly and to a greater extent in the cytoplasm than in the mitochondria, but did not necessarily signal greater changes in total NADH. The detection of depressed contractility before a fall in intracellular pH or a rise in intracellular lactate casts doubt on the postulate that an increase in hydrogen ion is the primary cause of hypoxic myocardial failure."}
{"id": "PMID:5756", "title": "Inhibition of glycolysis in hearts during ischemic perfusion.", "content": "Rates of glycolysis were determined in the isolated perfused rat heart under aerobic, anoxic, and ischemic conditions. The rate was accelerated in anoxic and was inhibited in ischemic tissue. Glycolytic inhibition developed at the level of glyceraldehyde-3-P dehydrogenase and was associated with accumulation of high levels of tissue lactate and H+.", "contents": "Inhibition of glycolysis in hearts during ischemic perfusion. Rates of glycolysis were determined in the isolated perfused rat heart under aerobic, anoxic, and ischemic conditions. The rate was accelerated in anoxic and was inhibited in ischemic tissue. Glycolytic inhibition developed at the level of glyceraldehyde-3-P dehydrogenase and was associated with accumulation of high levels of tissue lactate and H+."}
{"id": "PMID:5759", "title": "Muscarinic stimulation of cardiac guanylate cyclase.", "content": "Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (db-cAMP) at varying concentrations from 1 X 10(-4) M to 1 X 10(-3) M. A positive inotropic effect was observed with all concentrations of db-cAMP. Concomitant administration of 5 X 10(-4) M monobutyryl guanosine 3',5'-monophosphate and 1--2 X 10(-4) M db-cAMP did not produce an inotropic response. At the biochemical level cardiac guanyl cyclase activity is enhanced 2--3 times with acetylcholine and this enhancement is completely blocked by atropine. This increased activity appears to be the result of a decrease in the Michaelis constant (Km) for GTP. Calcium also produces a significant activation of guanyl cyclase activity.", "contents": "Muscarinic stimulation of cardiac guanylate cyclase. Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (db-cAMP) at varying concentrations from 1 X 10(-4) M to 1 X 10(-3) M. A positive inotropic effect was observed with all concentrations of db-cAMP. Concomitant administration of 5 X 10(-4) M monobutyryl guanosine 3',5'-monophosphate and 1--2 X 10(-4) M db-cAMP did not produce an inotropic response. At the biochemical level cardiac guanyl cyclase activity is enhanced 2--3 times with acetylcholine and this enhancement is completely blocked by atropine. This increased activity appears to be the result of a decrease in the Michaelis constant (Km) for GTP. Calcium also produces a significant activation of guanyl cyclase activity."}
{"id": "PMID:5760", "title": "Distribution of lysosome populations in rat cardiac tissue.", "content": "The post-nuclear fraction of rat heart tissue was fractionated by isopycnic zonal centrifugation in sucrose gradients, followed by differential centrifugation of the zonal fractions (rho-S fractionation). The distribution of 5 lysosomal acid hydrolases, a protease with neutral and alkaline activity and several marker enzymes for cell organelles (catalase, Ca2+-ATPase, cytochrome oxidase, glucose-6-phosphatase and muramidase) were studied. Three major lysosomal populations were described with equilibrium densities of 1.09, 1.17, and 1.23 gms cc-1 (omega2t = 1.54 X 10(11) rad2 sec-1), and a continuum in the size of these particles at the three different densities.", "contents": "Distribution of lysosome populations in rat cardiac tissue. The post-nuclear fraction of rat heart tissue was fractionated by isopycnic zonal centrifugation in sucrose gradients, followed by differential centrifugation of the zonal fractions (rho-S fractionation). The distribution of 5 lysosomal acid hydrolases, a protease with neutral and alkaline activity and several marker enzymes for cell organelles (catalase, Ca2+-ATPase, cytochrome oxidase, glucose-6-phosphatase and muramidase) were studied. Three major lysosomal populations were described with equilibrium densities of 1.09, 1.17, and 1.23 gms cc-1 (omega2t = 1.54 X 10(11) rad2 sec-1), and a continuum in the size of these particles at the three different densities."}
{"id": "PMID:5761", "title": "Phospholipase A and acid lipase activity during release of lysosomal hydrolases.", "content": "Hydrolysis of cardiac and hepatic lysosomal phospholipids by endogenous phospholipase A occurs during incubation at 37 degrees C at pH 5.0. Lysophospholipids and free fatty acids accumulate in association with release of hydrolases from the lysosomes into the supernatant. Acid-active neutral lipid lipases contribute to the release of free fatty acids. Albumin inhibits the production of these surface-active lipids as well as the release of hydrolases. The soluble phospholipase A is inhibited by albumin, soluble protein (cytoplasmic), heparin, and protamine sulfate. Thus, hydrolysis of lysosomal lipids, catalyzed by endogenous phospholipases, as well as acid-active neutral lipid lipases, may contribute significantly to the increased permeability, swelling, and subsequent lysis of lysosomes. Stabilization of the lysosomal membrane is associated with integrity of the structural lipids of the membrane.", "contents": "Phospholipase A and acid lipase activity during release of lysosomal hydrolases. Hydrolysis of cardiac and hepatic lysosomal phospholipids by endogenous phospholipase A occurs during incubation at 37 degrees C at pH 5.0. Lysophospholipids and free fatty acids accumulate in association with release of hydrolases from the lysosomes into the supernatant. Acid-active neutral lipid lipases contribute to the release of free fatty acids. Albumin inhibits the production of these surface-active lipids as well as the release of hydrolases. The soluble phospholipase A is inhibited by albumin, soluble protein (cytoplasmic), heparin, and protamine sulfate. Thus, hydrolysis of lysosomal lipids, catalyzed by endogenous phospholipases, as well as acid-active neutral lipid lipases, may contribute significantly to the increased permeability, swelling, and subsequent lysis of lysosomes. Stabilization of the lysosomal membrane is associated with integrity of the structural lipids of the membrane."}
{"id": "PMID:5762", "title": "Some properties of rat myocardial ornithine decarboxylase and the in vitro effects of nucleotides.", "content": "Myocardial ornithine decarboxylase appears to have characteristics similar to those of enzymes isolated from other tissues. Ornithine decarboxylase activity decreased very rapidly after the death of the animal. Storage of the cell sap fraction at 0 degrees C or -15 degrees C, however, led to only a small decrease in the enzyme activity up to 3 days after preparation. Pyridoxal phosphate at an optimum of 50 muM was essential for full enzyme activity. Thiol compounds did not increase the myocardial ornithine decarboxylase enzyme activity. The subcellular distribution of the enzyme in the myocardium was found to be different from that reported in other tissues. A partial purification of the enzyme was possible using the proteins precipitated at pH 5 from a cell-soluble fraction or by passing a soluble fraction through a Sephadex G 100 gel column. ATP, ADP, and AMP inhibited ornithine decarboxylase at high concentrations (5 mM), but GTP, CTP, and ITP inhibited at a 1 mM concentration and above.", "contents": "Some properties of rat myocardial ornithine decarboxylase and the in vitro effects of nucleotides. Myocardial ornithine decarboxylase appears to have characteristics similar to those of enzymes isolated from other tissues. Ornithine decarboxylase activity decreased very rapidly after the death of the animal. Storage of the cell sap fraction at 0 degrees C or -15 degrees C, however, led to only a small decrease in the enzyme activity up to 3 days after preparation. Pyridoxal phosphate at an optimum of 50 muM was essential for full enzyme activity. Thiol compounds did not increase the myocardial ornithine decarboxylase enzyme activity. The subcellular distribution of the enzyme in the myocardium was found to be different from that reported in other tissues. A partial purification of the enzyme was possible using the proteins precipitated at pH 5 from a cell-soluble fraction or by passing a soluble fraction through a Sephadex G 100 gel column. ATP, ADP, and AMP inhibited ornithine decarboxylase at high concentrations (5 mM), but GTP, CTP, and ITP inhibited at a 1 mM concentration and above."}
{"id": "PMID:5763", "title": "Comparative aspects of buffering capacity in muscle.", "content": "These findings are discussed in relation to the contention that a high buffer value is linked to a high work performance. This generalization does not extend to the \"white\" breast muscle of chicken. Its high buffer value is in part due to a high content of the dipeptides carnosine and anserine. Additionally, a hypothesis is advanced that muscle, e.g. pigeon breast muscle, can in part regulate intracellular pH by changes in the steady state concentrations of the glycolytic and citric acid cycle acids. Notably this form of pH regulation has no inherent energy requirement.", "contents": "Comparative aspects of buffering capacity in muscle. These findings are discussed in relation to the contention that a high buffer value is linked to a high work performance. This generalization does not extend to the \"white\" breast muscle of chicken. Its high buffer value is in part due to a high content of the dipeptides carnosine and anserine. Additionally, a hypothesis is advanced that muscle, e.g. pigeon breast muscle, can in part regulate intracellular pH by changes in the steady state concentrations of the glycolytic and citric acid cycle acids. Notably this form of pH regulation has no inherent energy requirement."}
{"id": "PMID:5764", "title": "Cardiac and skeletal muscle acid-base composition during metabolic acidosis in dogs.", "content": "Nephrectomized, open chested dogs were infused with 25-30 ml.kg(-1) body weight of 0.15 M NaCl (group I), 0.15 MHCl (Group II) or 0.3 M lactic acid (Group) III). Pulmonary ventilation was maintained constant in the three groups. Intracellular pH was calculated with the CO2 method. No significant intracellular or extracellular acid-base changes were produced in Group I. A similar degree of extracellular acidosis was achieved in Groups II and III. In spite of constant arterial PCO2, the PCO2 of mixed, coronary sinus and femoral vanous blood increased moderately after the infusion in Groups II and III. It was calculated that less than half of the HCl acid infused remained in the extracellular space. However, no significant changes were observed in the acid-base composition of skeletal muscle in either Group II or III. Comparison of the cardiac muscle cell acid-base composition of Group I with that of Groups II and III whows that metabolic acidosis of the degree and duration produced in these experiments does not produce appreciable myocardial acidosis.", "contents": "Cardiac and skeletal muscle acid-base composition during metabolic acidosis in dogs. Nephrectomized, open chested dogs were infused with 25-30 ml.kg(-1) body weight of 0.15 M NaCl (group I), 0.15 MHCl (Group II) or 0.3 M lactic acid (Group) III). Pulmonary ventilation was maintained constant in the three groups. Intracellular pH was calculated with the CO2 method. No significant intracellular or extracellular acid-base changes were produced in Group I. A similar degree of extracellular acidosis was achieved in Groups II and III. In spite of constant arterial PCO2, the PCO2 of mixed, coronary sinus and femoral vanous blood increased moderately after the infusion in Groups II and III. It was calculated that less than half of the HCl acid infused remained in the extracellular space. However, no significant changes were observed in the acid-base composition of skeletal muscle in either Group II or III. Comparison of the cardiac muscle cell acid-base composition of Group I with that of Groups II and III whows that metabolic acidosis of the degree and duration produced in these experiments does not produce appreciable myocardial acidosis."}
{"id": "PMID:5765", "title": "Dependence of CSF on plasma bicarbonate during hypocapnia and hypoxemic hypocapnia.", "content": "We have previoulsy shown pH compensation to be similar in CSF and arterial blood during chronic hypoxemic hypocapnia in man and pony, and postulated that the compensatory reduction in CSF [HCO3] was dependent upon corresponding changes in [HCO3]a. We tested this hypothesis in anesthetized, paralyzed dogs by determining the effects of 7 or 14 hours of hypocapnia (PaCO2 20 and 30 mm Hg), hypoxemia (PaO2 30, 38 and 48 mm Hg) and hypocapnic hypoxemia on CSF acid-base status. [hco3]a was either permitted to fall normally or was held near control levels by NaHCO3 infusion. In hypocapnia and hypoxemic hypocapnia, the decrease in [HCO3] and % pH compensation in CSF were less than or equal to that in arterial blood. Most (51-89%) of the compensatory decrease in CSF [HCO3] was prevented by preventing the corresponding reduction in [HCO3]a. This dependence of changes in CSF on plasma [HCO3] required a concurrent decrease in CSF PCO2, but was largely independent of variations in plasma pH. A minor but significant portion of the decrease in CSF [HCO3] was achieved independently of corresponding changes in [HCO3]a. The contribution of this local mechanism to CSF [HCO3] regulation increased with increasing severity of hypocapnia or hypoxemia and was usually associated with a selective increase in CSF lactate. It was concluded that [HCO3] regulation in the CSF during hypoxemic hypocapnia was primarily dependent upon, and therefore limited by, the concomitant decrease in plasma [HCO3].", "contents": "Dependence of CSF on plasma bicarbonate during hypocapnia and hypoxemic hypocapnia. We have previoulsy shown pH compensation to be similar in CSF and arterial blood during chronic hypoxemic hypocapnia in man and pony, and postulated that the compensatory reduction in CSF [HCO3] was dependent upon corresponding changes in [HCO3]a. We tested this hypothesis in anesthetized, paralyzed dogs by determining the effects of 7 or 14 hours of hypocapnia (PaCO2 20 and 30 mm Hg), hypoxemia (PaO2 30, 38 and 48 mm Hg) and hypocapnic hypoxemia on CSF acid-base status. [hco3]a was either permitted to fall normally or was held near control levels by NaHCO3 infusion. In hypocapnia and hypoxemic hypocapnia, the decrease in [HCO3] and % pH compensation in CSF were less than or equal to that in arterial blood. Most (51-89%) of the compensatory decrease in CSF [HCO3] was prevented by preventing the corresponding reduction in [HCO3]a. This dependence of changes in CSF on plasma [HCO3] required a concurrent decrease in CSF PCO2, but was largely independent of variations in plasma pH. A minor but significant portion of the decrease in CSF [HCO3] was achieved independently of corresponding changes in [HCO3]a. The contribution of this local mechanism to CSF [HCO3] regulation increased with increasing severity of hypocapnia or hypoxemia and was usually associated with a selective increase in CSF lactate. It was concluded that [HCO3] regulation in the CSF during hypoxemic hypocapnia was primarily dependent upon, and therefore limited by, the concomitant decrease in plasma [HCO3]."}
{"id": "PMID:5770", "title": "Response to jejunal acidification in man. I. Changes in composition of perfusate.", "content": "The jejunal disposal of perfused acid was studied in 11 control subjects and 12 patients with duodenal ulcer. It was found that the capacity to dispose of acid was saturable and was less than control in patients with duodenal ulcer. When the load of acid was small, all the acid disappeared from the jejunum and sodium bicarbonate could be aspirated. During acid perfusion there was secretion of water and electrolytes into the jejunum if the load of acid exceeded the dissipative capacity. Superimposed intravenous infusion of secretin and cholecystokinin increased acid disposal, particularly in patients with duodenal ulcer, and increased the associated rate of secretion of water and electrolytes or changed net absorption to net secretion. We conclude, firstly, that acid is removed from the jejunum by secreted bicarbonate, and secondly that the whole of the upper small intestine of patients with duodenal ulcer is functionally abnormal.", "contents": "Response to jejunal acidification in man. I. Changes in composition of perfusate. The jejunal disposal of perfused acid was studied in 11 control subjects and 12 patients with duodenal ulcer. It was found that the capacity to dispose of acid was saturable and was less than control in patients with duodenal ulcer. When the load of acid was small, all the acid disappeared from the jejunum and sodium bicarbonate could be aspirated. During acid perfusion there was secretion of water and electrolytes into the jejunum if the load of acid exceeded the dissipative capacity. Superimposed intravenous infusion of secretin and cholecystokinin increased acid disposal, particularly in patients with duodenal ulcer, and increased the associated rate of secretion of water and electrolytes or changed net absorption to net secretion. We conclude, firstly, that acid is removed from the jejunum by secreted bicarbonate, and secondly that the whole of the upper small intestine of patients with duodenal ulcer is functionally abnormal."}
{"id": "PMID:5771", "title": "The hydrolysis and absorption of conjugated folates in man.", "content": "After ingestion of synthetic PteGlu3 in physiological doses, the folate forms were studied in plasma obtained from human vena portae blood. Plasma conjugase was inhibited by rapid heat-denaturation. The folate forms were assayed with L. casei and S. faecalis and identified by thin-layer chromatography (biautography). Mono- and diglutamic folate was demonstrated in the portal plasma, indicating that intestinal hydrolysis precedes the absorption of conjugated folates. The pteroylpolyglutamate hydrolase activity in the human gastrointestinal tract was investigated. The activity was demonstrated in gastric juice, pancreatic juice, and intestinal mucosa. The highest activity was found in the pancreatic juice with a pH-optimum of 4.5. In gastric juice the pH-optimum for the enzyme was 3 and the activity half of that found in pancreatic juice. However, in view of the volumes of these fluids produced every day, the activity at physiological pH might be enough to hydrolyse the daily intake of conjugated folates in amounts of about 500 mug.", "contents": "The hydrolysis and absorption of conjugated folates in man. After ingestion of synthetic PteGlu3 in physiological doses, the folate forms were studied in plasma obtained from human vena portae blood. Plasma conjugase was inhibited by rapid heat-denaturation. The folate forms were assayed with L. casei and S. faecalis and identified by thin-layer chromatography (biautography). Mono- and diglutamic folate was demonstrated in the portal plasma, indicating that intestinal hydrolysis precedes the absorption of conjugated folates. The pteroylpolyglutamate hydrolase activity in the human gastrointestinal tract was investigated. The activity was demonstrated in gastric juice, pancreatic juice, and intestinal mucosa. The highest activity was found in the pancreatic juice with a pH-optimum of 4.5. In gastric juice the pH-optimum for the enzyme was 3 and the activity half of that found in pancreatic juice. However, in view of the volumes of these fluids produced every day, the activity at physiological pH might be enough to hydrolyse the daily intake of conjugated folates in amounts of about 500 mug."}
{"id": "PMID:5772", "title": "Erythroid differentiation of fetal, newborn and adult haemopoietic stem cells.", "content": "Erythroid regeneration was studied in lethally irradiated mice given transplants containing equivalent numbers of haemopoietic stem cells (i.e. CFU) from fetal liver, neonatal marrow or adult marrow. Adult marrow was taken from normal control mice, whose CFU for the most part were not in active cell cycle, as well as from phenylhydrazine-treated groups whose CFU were in similar state of proliferation (i.e. approximately 40-50% in DNA SYNTHESIS) AS THOSE DERIVED FROM FETAL LIVER AND NEONATAL MARROW. Splenic and femoral radioiron (59Fe) incorporation were measured at intervals after transplantation and were found to begin earliest in mice given fetal liver, then in animals given neonatal marrow and latest in recipients of adult marrow. Peripheral reticulocytes showed a similar pattern of recovery. The data reported herein suggest that the differences in erythroid regeneration evoked by transplants of fetal liver, neonatal marrow or adult marrow, are not solely attributed to the degree of proliferation in the pluripotential stem cell compartment. These data may, however, suggest a shorter doubling time for cells comprising the fetal and newborn committed erythroid compartments.", "contents": "Erythroid differentiation of fetal, newborn and adult haemopoietic stem cells. Erythroid regeneration was studied in lethally irradiated mice given transplants containing equivalent numbers of haemopoietic stem cells (i.e. CFU) from fetal liver, neonatal marrow or adult marrow. Adult marrow was taken from normal control mice, whose CFU for the most part were not in active cell cycle, as well as from phenylhydrazine-treated groups whose CFU were in similar state of proliferation (i.e. approximately 40-50% in DNA SYNTHESIS) AS THOSE DERIVED FROM FETAL LIVER AND NEONATAL MARROW. Splenic and femoral radioiron (59Fe) incorporation were measured at intervals after transplantation and were found to begin earliest in mice given fetal liver, then in animals given neonatal marrow and latest in recipients of adult marrow. Peripheral reticulocytes showed a similar pattern of recovery. The data reported herein suggest that the differences in erythroid regeneration evoked by transplants of fetal liver, neonatal marrow or adult marrow, are not solely attributed to the degree of proliferation in the pluripotential stem cell compartment. These data may, however, suggest a shorter doubling time for cells comprising the fetal and newborn committed erythroid compartments."}
{"id": "PMID:5773", "title": "Serological types of Diplococcus pneumoniae isolated from the respiratory tract of children with cystic fibrosis and children with other diseases.", "content": "The distribution of serological types of D. pneumoniae was investigated in 40 strains isolated from 26 children with cystic fibrosis and 57 strains isolated from 39 children with other diseases. All strains were isolated from sputum or tracheal secretion. The strains from cystic fibrosis patients belonged to 14 different serological types, the most prevalent were 19F, 19A and 3. The strains from the other group of children belonged to 20 different serological types, the most prevalent were 23F, 19F and 11A. The differences between the two groups of patients as to the prevalences of types were small, and it is concluded that no special serological types of D. pneumoniae are associated with cystic fibrosis.", "contents": "Serological types of Diplococcus pneumoniae isolated from the respiratory tract of children with cystic fibrosis and children with other diseases. The distribution of serological types of D. pneumoniae was investigated in 40 strains isolated from 26 children with cystic fibrosis and 57 strains isolated from 39 children with other diseases. All strains were isolated from sputum or tracheal secretion. The strains from cystic fibrosis patients belonged to 14 different serological types, the most prevalent were 19F, 19A and 3. The strains from the other group of children belonged to 20 different serological types, the most prevalent were 23F, 19F and 11A. The differences between the two groups of patients as to the prevalences of types were small, and it is concluded that no special serological types of D. pneumoniae are associated with cystic fibrosis."}
{"id": "PMID:5774", "title": "Catecholamine enzymes in the degenerative neurological disease idiopathic orthostatic hypotension.", "content": "Discrete brain areas and sympathetic ganglia obtained at autopsy from patients with idiopathic orthostatic hypotension were assayed for tyrosine hydroxylase and dopamine beta-hydroxylase. Dopamine beta-hydroxylase activity was decreased 7.5-fold in sympathetic ganglia, while tyrosine hydroxylase activity was reduced more than 50-fold in the pontine nucleus locus coeruleus. These observations indicate that noradrenergic neurons of both brain and ganglion are affected in idiopathic orthostatic hypotension, but suggest that the central and peripheral biochemical deficits differ.", "contents": "Catecholamine enzymes in the degenerative neurological disease idiopathic orthostatic hypotension. Discrete brain areas and sympathetic ganglia obtained at autopsy from patients with idiopathic orthostatic hypotension were assayed for tyrosine hydroxylase and dopamine beta-hydroxylase. Dopamine beta-hydroxylase activity was decreased 7.5-fold in sympathetic ganglia, while tyrosine hydroxylase activity was reduced more than 50-fold in the pontine nucleus locus coeruleus. These observations indicate that noradrenergic neurons of both brain and ganglion are affected in idiopathic orthostatic hypotension, but suggest that the central and peripheral biochemical deficits differ."}
{"id": "PMID:5775", "title": "Lymphocyte-induced angiogenesis in tumor-bearing mice.", "content": "The presence of a growing tumor can lead to a significant curtailment of a graft-versus-host reaction as measured by the ability of allogeneic spleen cells to induce a host vascular response. This interference with the normal pattern of immunological reactions may be a reason for the survival of tumors in an immunologically alien environment.", "contents": "Lymphocyte-induced angiogenesis in tumor-bearing mice. The presence of a growing tumor can lead to a significant curtailment of a graft-versus-host reaction as measured by the ability of allogeneic spleen cells to induce a host vascular response. This interference with the normal pattern of immunological reactions may be a reason for the survival of tumors in an immunologically alien environment."}
{"id": "PMID:5782", "title": "Clinical significance of the biotransformation of inhalation anesthetics.", "content": "Inhalation anesthetics, a class of drugs formerly believed to be biologically inert, are now recognized to undergo considerable biotransformation. The viscerotoxicity of certain anesthetics on kidney and liver can be explained in terms of metabolism. The entity of \"halothane hepatitis\" remains mechanistically and diagnostically a mystery, but if it exists, it could be due to abnormalities of biotransformation.", "contents": "Clinical significance of the biotransformation of inhalation anesthetics. Inhalation anesthetics, a class of drugs formerly believed to be biologically inert, are now recognized to undergo considerable biotransformation. The viscerotoxicity of certain anesthetics on kidney and liver can be explained in terms of metabolism. The entity of \"halothane hepatitis\" remains mechanistically and diagnostically a mystery, but if it exists, it could be due to abnormalities of biotransformation."}
{"id": "PMID:5783", "title": "Theoretical considerations in the vector control of filariasis.", "content": "In order to assist in assessing progress of vector control of filariasis a theoretical model is constructed, using retrospective data on infected persons removed to a vector-free situation. This shows that the decrease of microfilaraemia is not regular, but is gradual for the first 3 years and then more rapid, reaching zero at about 10 years. An estimate is made of the level to which the vector must be reduced before transmission of filariasis ceases, showing that the degree of efficiency required is considerably less than for malaria.", "contents": "Theoretical considerations in the vector control of filariasis. In order to assist in assessing progress of vector control of filariasis a theoretical model is constructed, using retrospective data on infected persons removed to a vector-free situation. This shows that the decrease of microfilaraemia is not regular, but is gradual for the first 3 years and then more rapid, reaching zero at about 10 years. An estimate is made of the level to which the vector must be reduced before transmission of filariasis ceases, showing that the degree of efficiency required is considerably less than for malaria."}
{"id": "PMID:5785", "title": "Intensive care in a hospital for Blacks. A review of 300 consecutive admissions.", "content": "Experinece with the first 300 patients in a new Intensive Care Unit for Blacks is presented. Causes of death and specific problems are considered in detail.", "contents": "Intensive care in a hospital for Blacks. A review of 300 consecutive admissions. Experinece with the first 300 patients in a new Intensive Care Unit for Blacks is presented. Causes of death and specific problems are considered in detail."}
{"id": "PMID:5786", "title": "The management of hernias, hydroceles and undescended testes.", "content": "The management of hernias, hydroceles and undescended testicles is reviewed on the basis of current practice as reported in recent literature and of the author's experience at Addington Hospital, Durban.", "contents": "The management of hernias, hydroceles and undescended testes. The management of hernias, hydroceles and undescended testicles is reviewed on the basis of current practice as reported in recent literature and of the author's experience at Addington Hospital, Durban."}
{"id": "PMID:5793", "title": "Experimental stimulation of cell-mediated immunity without concomitant stimulation of humoral immunity in graft-versus-host immunosuppressed mice.", "content": "The immunosuppressive effect of the graft-versus-host (GVH) reaction was studied in CBA X A F1 (CAF1) mice which had been rendered immunologically unresponsive by the injection of parental A strain lymphoid cells (GVH mice). Suppression of both cell-mediated and humoral immune responses was demonstrated by the prolonged survival of C57BL/6 (B6) skin allografts and by the inability of GVH mice to produce detectable antibody following stimulation with sheep erythrocytes (SRBC). Appropriate stimulation of GVH mice induced cell-mediated immune reactions to xeno- and allogeneic antigens while the humoral immune responses to the same antigens remained suppressed. Multiple challenges of the GVH mice with B6 tissue caused a rapid rejection of subsequent B6 skin grafts but failed to stimulate the production of any detectable antibodies to B6 allotransplantation antigens. Sensitization of GVH mice with SRBC in Freund's complete adjuvant stimulated a delayed hypersensitivity response to SRBC, although no humoral response to SRBC could be detected, even after three challenges with SRBC. The experimental results are discussed in terms of a proposed model for GVH-induced immunosuppression.", "contents": "Experimental stimulation of cell-mediated immunity without concomitant stimulation of humoral immunity in graft-versus-host immunosuppressed mice. The immunosuppressive effect of the graft-versus-host (GVH) reaction was studied in CBA X A F1 (CAF1) mice which had been rendered immunologically unresponsive by the injection of parental A strain lymphoid cells (GVH mice). Suppression of both cell-mediated and humoral immune responses was demonstrated by the prolonged survival of C57BL/6 (B6) skin allografts and by the inability of GVH mice to produce detectable antibody following stimulation with sheep erythrocytes (SRBC). Appropriate stimulation of GVH mice induced cell-mediated immune reactions to xeno- and allogeneic antigens while the humoral immune responses to the same antigens remained suppressed. Multiple challenges of the GVH mice with B6 tissue caused a rapid rejection of subsequent B6 skin grafts but failed to stimulate the production of any detectable antibodies to B6 allotransplantation antigens. Sensitization of GVH mice with SRBC in Freund's complete adjuvant stimulated a delayed hypersensitivity response to SRBC, although no humoral response to SRBC could be detected, even after three challenges with SRBC. The experimental results are discussed in terms of a proposed model for GVH-induced immunosuppression."}
{"id": "PMID:5794", "title": "[The hematopoietic colony-forming cell--object of experimental study].", "content": "Studies dealing with the colony-forming cell as a subject of experimental research are reviewed. The techniques of cultivation of colony-forming cells, their proliferation, differentiation and self-renewal have been considered.", "contents": "[The hematopoietic colony-forming cell--object of experimental study]. Studies dealing with the colony-forming cell as a subject of experimental research are reviewed. The techniques of cultivation of colony-forming cells, their proliferation, differentiation and self-renewal have been considered."}
{"id": "PMID:5796", "title": "Abnormal liver enzymes and human chorionic gonadotropin elevation in abdominal testicular seminoma.", "content": "A case of seminoma in an abdominal testis is presented in which abnormal liver enzyme as well as elevated human chorionic gonadotropin levels were present which returned to normal after surgical extirpation of the primary lesion. A review of pertinent literature and implications of these unusual findings are presented.", "contents": "Abnormal liver enzymes and human chorionic gonadotropin elevation in abdominal testicular seminoma. A case of seminoma in an abdominal testis is presented in which abnormal liver enzyme as well as elevated human chorionic gonadotropin levels were present which returned to normal after surgical extirpation of the primary lesion. A review of pertinent literature and implications of these unusual findings are presented."}
{"id": "PMID:5801", "title": "[Clinical evaluation of the effectiveness of different surgical interventions in peptic ulcer].", "content": "The clinical status, secretory and motor activity of the stomach were studied in 213 patients showing ulcerous disease prior to surgery and in 153 operated patients. The most favourable results were noted after resection of two thirds of the stomach in Billroth I modification with preservation of the pyloric compressor. These patients along with suppression of acid-formation retained normal portional evacuation of the gastric content. Selective vagotomy with resection of the ulcer and pyloroplasty in a number of patients produced no considerable reduction in acid-formation both in the early postoperative period and in later terms.", "contents": "[Clinical evaluation of the effectiveness of different surgical interventions in peptic ulcer]. The clinical status, secretory and motor activity of the stomach were studied in 213 patients showing ulcerous disease prior to surgery and in 153 operated patients. The most favourable results were noted after resection of two thirds of the stomach in Billroth I modification with preservation of the pyloric compressor. These patients along with suppression of acid-formation retained normal portional evacuation of the gastric content. Selective vagotomy with resection of the ulcer and pyloroplasty in a number of patients produced no considerable reduction in acid-formation both in the early postoperative period and in later terms."}
{"id": "PMID:5802", "title": "[Comparative study of the optimum pH value of serum alkaline phosphatase in various species of farm animals].", "content": "Investigations were carried out on the alkaline phosphatase in the sera of cattle, horses, pigs, sheep, goats, and chickens, the pH value of the buffer used being 9.0-9.8-10.0-10.2-10.6 and 11.0, and the method applied--that of Richterich. The pH value at which the serum alkaline phosphatase in the various farm animals and birds was most active was found to vary to a large extent. Optimal values for the enzyme's activity usually range as follows: cattle, 10.2; pigs and goats, 10.0; sheep,--10.2; horses,--9.8; chickens,--10.6.", "contents": "[Comparative study of the optimum pH value of serum alkaline phosphatase in various species of farm animals]. Investigations were carried out on the alkaline phosphatase in the sera of cattle, horses, pigs, sheep, goats, and chickens, the pH value of the buffer used being 9.0-9.8-10.0-10.2-10.6 and 11.0, and the method applied--that of Richterich. The pH value at which the serum alkaline phosphatase in the various farm animals and birds was most active was found to vary to a large extent. Optimal values for the enzyme's activity usually range as follows: cattle, 10.2; pigs and goats, 10.0; sheep,--10.2; horses,--9.8; chickens,--10.6."}
{"id": "PMID:5809", "title": "The electrolyte pattern of the gastric secretion from the vervet monkey.", "content": "The output of acid, chloride, sodium and potassium in gastric washings from the Vervet monkey have been measured under basal conditions and while stimulating the secretion with two doses of pentagastrin (one dose submaximal, the other dose supramaximal). The output during washings with different weak electrolyte solutions (5 mEq/1 NaC1, KCl, or HCl or 0.36 M Glycine) are compared. The results show that the composition of the secretion was independent of the composition of the rinsing fluid in the stomach except that glycine stimulated acid and potassium secretion when the monkey was not stimulated by pentagastrin. These observations and the composition of the gastric secretion of the Vervet monkey are discussed in the light of the \"two-component\" and \"exchange\" models of gastric secretion, and which compared with the gastric juice obtained from humans under similar conditions.", "contents": "The electrolyte pattern of the gastric secretion from the vervet monkey. The output of acid, chloride, sodium and potassium in gastric washings from the Vervet monkey have been measured under basal conditions and while stimulating the secretion with two doses of pentagastrin (one dose submaximal, the other dose supramaximal). The output during washings with different weak electrolyte solutions (5 mEq/1 NaC1, KCl, or HCl or 0.36 M Glycine) are compared. The results show that the composition of the secretion was independent of the composition of the rinsing fluid in the stomach except that glycine stimulated acid and potassium secretion when the monkey was not stimulated by pentagastrin. These observations and the composition of the gastric secretion of the Vervet monkey are discussed in the light of the \"two-component\" and \"exchange\" models of gastric secretion, and which compared with the gastric juice obtained from humans under similar conditions."}
{"id": "PMID:5811", "title": "[The acid-base balance in the CSF of normal subjects regulatory mechanisms (author's transl)].", "content": "1. The acid-base balance (pH, pCO2 and HCO-3) of 23 normal subjects was determined both in arterialized capillary blood and in the CSF. 2. Statistically significant correlations (determined by means of Spearman's rank correlation) were found between: pCO2 in arterialized blood and CSF pH (Rs=--0.372, p is less than 0.05), pCO2 in the CSF and CSF pH (Rs=--0.421, p is less than 0.05), HCO-3 in the CSF and in arterialized blood (Rs=0.623, p is less than 0.05), blood pH and CSF pH (Rs=0.485, p is less than 0.025), pCO2 in the CSF and HCO-3 in the CSF (Rs=0.559, p is less than 0.005). 3. The regulatory mechanisms of the CSF acid-base balance in normal subjects and also in patients with extra-neural or CNS disturbances are discussed.", "contents": "[The acid-base balance in the CSF of normal subjects regulatory mechanisms (author's transl)]. 1. The acid-base balance (pH, pCO2 and HCO-3) of 23 normal subjects was determined both in arterialized capillary blood and in the CSF. 2. Statistically significant correlations (determined by means of Spearman's rank correlation) were found between: pCO2 in arterialized blood and CSF pH (Rs=--0.372, p is less than 0.05), pCO2 in the CSF and CSF pH (Rs=--0.421, p is less than 0.05), HCO-3 in the CSF and in arterialized blood (Rs=0.623, p is less than 0.05), blood pH and CSF pH (Rs=0.485, p is less than 0.025), pCO2 in the CSF and HCO-3 in the CSF (Rs=0.559, p is less than 0.005). 3. The regulatory mechanisms of the CSF acid-base balance in normal subjects and also in patients with extra-neural or CNS disturbances are discussed."}
{"id": "PMID:5812", "title": "[The diagnosis of cholestasis: lipoprotein X (LP-X) (author's transl)].", "content": "The diagnostic specificity of a new method to detect obstructive jaundice by determination of lipoprotein X (LP-X) was tested in 144 patients with different kinds of hepatic diseases and compared with the usual chemical \"obstructive jaundice specific\" tests, such as bilirubin, SGOT, SGPT, alkaline phosphatase, LAP and gamma-GT. The LP-X test was performed by using all-in test kit LP-X Rapidophor\" low-voltage electrophoresis of Immuno AG/Wien. The results were correlated with the histological classification of the liver biopsy specimen. In 82% of the histologically verified cases of obstructive jaundice the result of the LP-X test was positive, whilst in 98.5% of the histologically negative cases the result of the LP-X test was negative. Hence, this LP-X method proved superior to chemical methods in providing a clear-cut positive or negative answer to the presence of cholestasis. Furthermore, the LP-X test was suitable for long-term follow-up investigation of patients with obstructive jaundice.", "contents": "[The diagnosis of cholestasis: lipoprotein X (LP-X) (author's transl)]. The diagnostic specificity of a new method to detect obstructive jaundice by determination of lipoprotein X (LP-X) was tested in 144 patients with different kinds of hepatic diseases and compared with the usual chemical \"obstructive jaundice specific\" tests, such as bilirubin, SGOT, SGPT, alkaline phosphatase, LAP and gamma-GT. The LP-X test was performed by using all-in test kit LP-X Rapidophor\" low-voltage electrophoresis of Immuno AG/Wien. The results were correlated with the histological classification of the liver biopsy specimen. In 82% of the histologically verified cases of obstructive jaundice the result of the LP-X test was positive, whilst in 98.5% of the histologically negative cases the result of the LP-X test was negative. Hence, this LP-X method proved superior to chemical methods in providing a clear-cut positive or negative answer to the presence of cholestasis. Furthermore, the LP-X test was suitable for long-term follow-up investigation of patients with obstructive jaundice."}
{"id": "PMID:5813", "title": "[The effects of flunitrazepam (rohypnol) on respiration (author's transl)].", "content": "The effects of flunitrazepam (0.03 mg/kg administered intravenously over a two-minute period) was investigated in 11 healthy volunteers with normal pulmonary function. Spirometer tracings were recorded continuously by the Siregnost FD 40 and blood gas measurements were performed by the Harnoncourt AVL gas analyzer. Flunitrazepam produced a characteristic cyclical hypoventilation/hyperventilation pattern lasting 15 min., followed by quiet sleeping rhythms. The duration of action was 20 min. There was a significant fall in PCO2, whilst the  CO2 tension showed a significant rise. Changes in pH were in accordance with respiratory acidosis. Apnoea did not occur after the administration of flunitrazepam.", "contents": "[The effects of flunitrazepam (rohypnol) on respiration (author's transl)]. The effects of flunitrazepam (0.03 mg/kg administered intravenously over a two-minute period) was investigated in 11 healthy volunteers with normal pulmonary function. Spirometer tracings were recorded continuously by the Siregnost FD 40 and blood gas measurements were performed by the Harnoncourt AVL gas analyzer. Flunitrazepam produced a characteristic cyclical hypoventilation/hyperventilation pattern lasting 15 min., followed by quiet sleeping rhythms. The duration of action was 20 min. There was a significant fall in PCO2, whilst the  CO2 tension showed a significant rise. Changes in pH were in accordance with respiratory acidosis. Apnoea did not occur after the administration of flunitrazepam."}
{"id": "PMID:5814", "title": "[Immunosuppressive therapy in renal disease (author's transl)].", "content": "Since immunological events were found to be pathogenetically involved in various forms of glomerulonephritis, corticosteroids and immunosuppressive drugs were introduced in the treatment of nephritis. However, as opposed to the findings in the paediatric nephrotic syndrome, controlled and multicentric trials with immunosuppressive therapy revealed disappointing results in the management of renal disease in adults. Significantly better results under immunosuppressive therapy, were seen only in the nephrotic syndrome based on the so-called \"no changes\" or \"minimal changes\" nephritis. In chronic membranous and proliferative glomerulonephritis the clinical course in the treated group was not statistically different from that of the untreated group. In some disorders of connective tissues, such as systemic lupus erythematosus, polyarteritis nodosa and Wegener's granulomatosis, corticosteroids and immunosuppressive agents seem to exert a favourable effect on the course of renal disease. Encouraging results concerning the combined use of immunosuppressive drugs, anticoagulants and platelet aggregation inhibitors in mesangiocapillary (membrano-proliferative) glomerulonephritis and rapidly progressive nephritis have also been presented. Several factors such as incomplete immunosuppression, druginduced antigen tolerance and increased immune complex formation as a consequence of inhibited antibody production may contribute to the fact that many patients with different forms of nephritis do not benefit from long-term immunosuppressive therapy.", "contents": "[Immunosuppressive therapy in renal disease (author's transl)]. Since immunological events were found to be pathogenetically involved in various forms of glomerulonephritis, corticosteroids and immunosuppressive drugs were introduced in the treatment of nephritis. However, as opposed to the findings in the paediatric nephrotic syndrome, controlled and multicentric trials with immunosuppressive therapy revealed disappointing results in the management of renal disease in adults. Significantly better results under immunosuppressive therapy, were seen only in the nephrotic syndrome based on the so-called \"no changes\" or \"minimal changes\" nephritis. In chronic membranous and proliferative glomerulonephritis the clinical course in the treated group was not statistically different from that of the untreated group. In some disorders of connective tissues, such as systemic lupus erythematosus, polyarteritis nodosa and Wegener's granulomatosis, corticosteroids and immunosuppressive agents seem to exert a favourable effect on the course of renal disease. Encouraging results concerning the combined use of immunosuppressive drugs, anticoagulants and platelet aggregation inhibitors in mesangiocapillary (membrano-proliferative) glomerulonephritis and rapidly progressive nephritis have also been presented. Several factors such as incomplete immunosuppression, druginduced antigen tolerance and increased immune complex formation as a consequence of inhibited antibody production may contribute to the fact that many patients with different forms of nephritis do not benefit from long-term immunosuppressive therapy."}
{"id": "PMID:5815", "title": "[Infusion therapy with mif (melanocyte inhibiting factor) in Parkinson's disease (author's transl)].", "content": "On the basis of reports in the literature and of our own clinical experience it appears that melanocyte inhibiting factor (MIF) is a very promising therapeutic agent in the management of Parkinson's disease. Besides theoretical considerations relating to biochemical and pathophysiological spheres, the question of the current dosage for clinical usage seems to be of the utmost importance. We are of the opinion that the currently-employed dosage of 400 mg daily is still too low. Hence, the present investigation will be continued with a view to establishing the optimum dosage for maximal therapeutic effect.", "contents": "[Infusion therapy with mif (melanocyte inhibiting factor) in Parkinson's disease (author's transl)]. On the basis of reports in the literature and of our own clinical experience it appears that melanocyte inhibiting factor (MIF) is a very promising therapeutic agent in the management of Parkinson's disease. Besides theoretical considerations relating to biochemical and pathophysiological spheres, the question of the current dosage for clinical usage seems to be of the utmost importance. We are of the opinion that the currently-employed dosage of 400 mg daily is still too low. Hence, the present investigation will be continued with a view to establishing the optimum dosage for maximal therapeutic effect."}
{"id": "PMID:5822", "title": "Implication of rifampicin-quinone in the irreversible binding of rifampicin to macromolecules.", "content": "1. When [3H]rifampicin is incubated with rat liver microsomes or rat liver homogenate, minor amounts are bound irreversibly to protein. This effect does not depend on the presence of NAD, NADH, NADP or NADPH. 2. Rifampicin is autoxidized at physiological pH. The product of autoxidation, rifampicin-quinone, if incubated with albumin, shows a much greater irreversible binding to the protein than the parent compound rifampicin. Hence it is concluded that rifampicin may bind irreversibly to proteins in a non-enzymic reaction after autoxidation to rifampicin-quinone. 3. Rifampicin-quinone also binds irreversibly to RNA and poly-L-lysine, if incubated with these compounds. This suggests that free amino groups of protein or RNA are involved in the binding. 4. 48 h after dosage of [3H]rifampicin (33 mg/kg) to rats, 29-2 +/- 4-1 (S.D.) pmol are bound irreversibly to 1 mg liver RNA, 15.8 +/- 8-1 pmol to 1 mg liver protein and 5-0 +/- 0-47 pmol to 1 mg protein in brain tissue. 5. Microsomal NADPH-cytochromcin-quinone to rifampicin. The KM of this reaction is 10(-4) M. Induction of the NADPH-cytochrome c reductase by pre-treatment of rats with 20 mg/kg rifampicin over 5 days results in a corresponding increase of increase of rifampicin-quinone reduction. 6. These results suggest that microsomal NADPH-cytochrome c reductase prevents accumulation of higher amounts of possibly toxic rifampicin-quinone by reduction to rifampicin.", "contents": "Implication of rifampicin-quinone in the irreversible binding of rifampicin to macromolecules. 1. When [3H]rifampicin is incubated with rat liver microsomes or rat liver homogenate, minor amounts are bound irreversibly to protein. This effect does not depend on the presence of NAD, NADH, NADP or NADPH. 2. Rifampicin is autoxidized at physiological pH. The product of autoxidation, rifampicin-quinone, if incubated with albumin, shows a much greater irreversible binding to the protein than the parent compound rifampicin. Hence it is concluded that rifampicin may bind irreversibly to proteins in a non-enzymic reaction after autoxidation to rifampicin-quinone. 3. Rifampicin-quinone also binds irreversibly to RNA and poly-L-lysine, if incubated with these compounds. This suggests that free amino groups of protein or RNA are involved in the binding. 4. 48 h after dosage of [3H]rifampicin (33 mg/kg) to rats, 29-2 +/- 4-1 (S.D.) pmol are bound irreversibly to 1 mg liver RNA, 15.8 +/- 8-1 pmol to 1 mg liver protein and 5-0 +/- 0-47 pmol to 1 mg protein in brain tissue. 5. Microsomal NADPH-cytochromcin-quinone to rifampicin. The KM of this reaction is 10(-4) M. Induction of the NADPH-cytochrome c reductase by pre-treatment of rats with 20 mg/kg rifampicin over 5 days results in a corresponding increase of increase of rifampicin-quinone reduction. 6. These results suggest that microsomal NADPH-cytochrome c reductase prevents accumulation of higher amounts of possibly toxic rifampicin-quinone by reduction to rifampicin."}
{"id": "PMID:5823", "title": "[Bacteriological examinations of bronchial secretion in children with non-specific bronchopulmonary disease (author's transl)].", "content": "One thousand specimens of bronchial secretion from children with non-specific respiratory diseases have been examined bacteriologically. In spite of the complex nature of acute and especially of chronic respiratory disease the role of bacterial infection should not be underestimated. Thirty per cent of the specimens were sterile. More than 20 per cent of the bacterial species isolated from bronchial secretion were pathogenic. Relatively frequent was the isolation of E. coli and of pathogenic staphylococci. Nearly 40 per cent of all isolated bacteria were alpha-haemolytic streptococci. The latter have been found more frequently in children with, than in children without bronchological alterations. The pathogenicity of alpha-haemolytic streptococci in the bronchial tree is discussed.", "contents": "[Bacteriological examinations of bronchial secretion in children with non-specific bronchopulmonary disease (author's transl)]. One thousand specimens of bronchial secretion from children with non-specific respiratory diseases have been examined bacteriologically. In spite of the complex nature of acute and especially of chronic respiratory disease the role of bacterial infection should not be underestimated. Thirty per cent of the specimens were sterile. More than 20 per cent of the bacterial species isolated from bronchial secretion were pathogenic. Relatively frequent was the isolation of E. coli and of pathogenic staphylococci. Nearly 40 per cent of all isolated bacteria were alpha-haemolytic streptococci. The latter have been found more frequently in children with, than in children without bronchological alterations. The pathogenicity of alpha-haemolytic streptococci in the bronchial tree is discussed."}
{"id": "PMID:5830", "title": "Biochemical and histochemical studies on non-specific phosphomonoesterases of swine kidney worm Stephanurus dentatus (Diesing, 1839).", "content": "Biochemical and histochemical studies have been made on non-specific acid and alkaline phosphomonoesterases of S. dentatus. The two forms of acid phosphomonoesterases have been found active at pH 4.0 and 6.0. The pH optima for the two forms of aklaline phosphomonoesterases lie at 8.0 and 10.0. Studies on the distribution of acid and alkaline phosphomonoesterases in various tissues have revealed an abundance of acid phosphomonoesterase in various parts of the alimentary canal and various organs of the reproductive system. The excretory ducts show alkaline phosphomonoesterase activity only.", "contents": "Biochemical and histochemical studies on non-specific phosphomonoesterases of swine kidney worm Stephanurus dentatus (Diesing, 1839). Biochemical and histochemical studies have been made on non-specific acid and alkaline phosphomonoesterases of S. dentatus. The two forms of acid phosphomonoesterases have been found active at pH 4.0 and 6.0. The pH optima for the two forms of aklaline phosphomonoesterases lie at 8.0 and 10.0. Studies on the distribution of acid and alkaline phosphomonoesterases in various tissues have revealed an abundance of acid phosphomonoesterase in various parts of the alimentary canal and various organs of the reproductive system. The excretory ducts show alkaline phosphomonoesterase activity only."}
{"id": "PMID:5827", "title": "Reversal of dibromothymoquinone inhibition of photosynthetic electron flow by thiol compounds.", "content": "Dibromothymoquinone inhibits photosynthetic NADP reduction by broken chloroplasts. The inhibition of electron flow and coupled ATP formation is effectively reversed by the addition of thiol compounds.", "contents": "Reversal of dibromothymoquinone inhibition of photosynthetic electron flow by thiol compounds. Dibromothymoquinone inhibits photosynthetic NADP reduction by broken chloroplasts. The inhibition of electron flow and coupled ATP formation is effectively reversed by the addition of thiol compounds."}
{"id": "PMID:5828", "title": "On the mechanism of the acridine orange sensitized photodynamic inactivation of lysozyme. I. Basic kinetics.", "content": "The kinetics of the photodynamic desactivation of lysozyme in presence of acridine orange as the sensitizer have been investigated in detail varying oxygen, protein, dye concentration, ionic strength and pH value. The kinetics can be approximately described as an over all pseudo-first-order rate process. Changing the solvent from water to D2O or by quenching experiments in presence of azide ions it could be shown that the desactivation of lysozyme is caused exclusively by singlet oxygen. The excited oxygen occurs via the triplet state of the dye with a rate constant considerably lower than that to be expected for a diffusionally controlled reaction. Singlet oxygen react chemically (desactivation, k=2.9 X 10(7) m(-1) sec(-1)) and physically (quenching process, k=4.1 X 10(8) m(-1) sec(-1)) with the enzyme. The kinetical analysis shows that additional chemical reaction between singlet oxygen and lysozyme would have only little influence on the kinetics of the desactivation as long as their products would be enzymatically active and their kinetical constants would be less than about 1 X 10(8) m(-1) sec(-1)).", "contents": "On the mechanism of the acridine orange sensitized photodynamic inactivation of lysozyme. I. Basic kinetics. The kinetics of the photodynamic desactivation of lysozyme in presence of acridine orange as the sensitizer have been investigated in detail varying oxygen, protein, dye concentration, ionic strength and pH value. The kinetics can be approximately described as an over all pseudo-first-order rate process. Changing the solvent from water to D2O or by quenching experiments in presence of azide ions it could be shown that the desactivation of lysozyme is caused exclusively by singlet oxygen. The excited oxygen occurs via the triplet state of the dye with a rate constant considerably lower than that to be expected for a diffusionally controlled reaction. Singlet oxygen react chemically (desactivation, k=2.9 X 10(7) m(-1) sec(-1)) and physically (quenching process, k=4.1 X 10(8) m(-1) sec(-1)) with the enzyme. The kinetical analysis shows that additional chemical reaction between singlet oxygen and lysozyme would have only little influence on the kinetics of the desactivation as long as their products would be enzymatically active and their kinetical constants would be less than about 1 X 10(8) m(-1) sec(-1))."}
{"id": "PMID:5829", "title": "Photoreactions of cytochrome b6 and cytochrome f in chloroplast photosystem I fragments.", "content": "Photosystem I fragments were prepared by digitonin treatment of spinach chloroplasts. The midpoint potential of cytochrome b6 in the fragments is close to 0V, showing a one electron transition. No cytochrome b559 was detectable, neither in difference absorption spectra nor in light-induced absorbance changes. In the absence of added cofactors only cytochrome b6 photoreduction can be observed. This photoreduction is stimulated by ferredoxin. Ferredoxin-NADP+ reductase appears not to be involved in cytochrome b6 reduction. Photooxidation of cytochrome b6 is dependent on plastocyanin addition and inhibited by DBMIB, a plastoquinone antagonist. Addition of plastocyanin restores cytochrome f photooxidation as well, reacting quite specifically in about equimolar concentrations to bound cytochrome f. The stimulation of cytochrome f oxidation is abolished by an antibody prepared against plastocyanin, indicating a surface location of plastocyanin in digitonin treated membranes. Biphasic kinetics of dark-reduction of cytochrome f by ascorbate indicate that part of this cytochrome f is relatively inaccessible in the membrane. After preillumination a monophasic reduction is observed and the slowly oxidized component is absent. Illumination in the presence of plastocyanin causes a fast and complete reduction of cytochrome f, suggesting equilibration of cytochrome f with added plastocyanin, residing in the membrane surface. It appears that actinic light causes conformation and/or structural changes in the membrane of these digitonin fragments, influencing cytochrome f asseccibility.", "contents": "Photoreactions of cytochrome b6 and cytochrome f in chloroplast photosystem I fragments. Photosystem I fragments were prepared by digitonin treatment of spinach chloroplasts. The midpoint potential of cytochrome b6 in the fragments is close to 0V, showing a one electron transition. No cytochrome b559 was detectable, neither in difference absorption spectra nor in light-induced absorbance changes. In the absence of added cofactors only cytochrome b6 photoreduction can be observed. This photoreduction is stimulated by ferredoxin. Ferredoxin-NADP+ reductase appears not to be involved in cytochrome b6 reduction. Photooxidation of cytochrome b6 is dependent on plastocyanin addition and inhibited by DBMIB, a plastoquinone antagonist. Addition of plastocyanin restores cytochrome f photooxidation as well, reacting quite specifically in about equimolar concentrations to bound cytochrome f. The stimulation of cytochrome f oxidation is abolished by an antibody prepared against plastocyanin, indicating a surface location of plastocyanin in digitonin treated membranes. Biphasic kinetics of dark-reduction of cytochrome f by ascorbate indicate that part of this cytochrome f is relatively inaccessible in the membrane. After preillumination a monophasic reduction is observed and the slowly oxidized component is absent. Illumination in the presence of plastocyanin causes a fast and complete reduction of cytochrome f, suggesting equilibration of cytochrome f with added plastocyanin, residing in the membrane surface. It appears that actinic light causes conformation and/or structural changes in the membrane of these digitonin fragments, influencing cytochrome f asseccibility."}
{"id": "PMID:5836", "title": "[Extraction and concentration of Clostridium botulinum toxins from specimens (author's transl)].", "content": "In order to detect minimal amounts of Clostridium botulinum toxins in animal tissue or food specimens it is necessary to use an extraction method which results in concentration of the botulinal toxins. In the present examinations, artificially contaminated canned beans were used to develop a suitable procedure for extraction and concentration of botulinal toxins A-E. The procedure consisted of 4 steps: 1. Canned beans were diluted 1:2 with 0.1 m phosphate buffer pH 6.0. 2. The diluted material was homogenised with an \"Ultra-Turrax\" homogeniser for 20 sec. 3. The monogenised material was centrifuged at 4000 rpm for 30 min. 4. 15 ml of supernatant was concentrated using a \"Millipore ultrafiltration chamber\" (with a membrane capable of excluding all material with a molecular weight above 25,000). A pressure of 1.5 atmospheres was applied until the terminal volume was 0.5 ml. Following extraction and concentration, the samples were assayed for botulinal toxin in mice. Using this assay the concentration of the five toxins were shown to be as follows: Type A toxin: 19.0-fold toxin concentration Type B toxin: 14.8-fold toxin concentration Type C toxin: 20.6-fold toxin concentration Type D toxin: 28.2-fold toxin concentration Type E toxin: 112.2-fold toxin concentration", "contents": "[Extraction and concentration of Clostridium botulinum toxins from specimens (author's transl)]. In order to detect minimal amounts of Clostridium botulinum toxins in animal tissue or food specimens it is necessary to use an extraction method which results in concentration of the botulinal toxins. In the present examinations, artificially contaminated canned beans were used to develop a suitable procedure for extraction and concentration of botulinal toxins A-E. The procedure consisted of 4 steps: 1. Canned beans were diluted 1:2 with 0.1 m phosphate buffer pH 6.0. 2. The diluted material was homogenised with an \"Ultra-Turrax\" homogeniser for 20 sec. 3. The monogenised material was centrifuged at 4000 rpm for 30 min. 4. 15 ml of supernatant was concentrated using a \"Millipore ultrafiltration chamber\" (with a membrane capable of excluding all material with a molecular weight above 25,000). A pressure of 1.5 atmospheres was applied until the terminal volume was 0.5 ml. Following extraction and concentration, the samples were assayed for botulinal toxin in mice. Using this assay the concentration of the five toxins were shown to be as follows: Type A toxin: 19.0-fold toxin concentration Type B toxin: 14.8-fold toxin concentration Type C toxin: 20.6-fold toxin concentration Type D toxin: 28.2-fold toxin concentration Type E toxin: 112.2-fold toxin concentration"}
{"id": "PMID:5834", "title": "Bacterial meningitis in infancy and childhood in Lusaka (One year prospective sturdy).", "content": "In approximately 10,000 admissions in a 12 months period, at University Teaching Hospital, Lusaka 85 cases of meningitis were recorded. The signs and symptoms in these patients do not greatly differ from other similar studies in Africa. The commonest organism isolated was pneumococcus. There was high mortality rate which was to a large extent due to parents not bringing their children to hospital early enough for medical treatment to be instituted. This is borne out by the fact that 50% of the children with meningitis died within the first 24 hours. The C.S.F. protein and peripheral white blood count may be of prognostic value. Spasticity, cranial nerve palsises hydrocephalus and subdural effusion were the commonest complications.", "contents": "Bacterial meningitis in infancy and childhood in Lusaka (One year prospective sturdy). In approximately 10,000 admissions in a 12 months period, at University Teaching Hospital, Lusaka 85 cases of meningitis were recorded. The signs and symptoms in these patients do not greatly differ from other similar studies in Africa. The commonest organism isolated was pneumococcus. There was high mortality rate which was to a large extent due to parents not bringing their children to hospital early enough for medical treatment to be instituted. This is borne out by the fact that 50% of the children with meningitis died within the first 24 hours. The C.S.F. protein and peripheral white blood count may be of prognostic value. Spasticity, cranial nerve palsises hydrocephalus and subdural effusion were the commonest complications."}
{"id": "PMID:5840", "title": "Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in infants.", "content": "Cerebral blood flow (CBF) and cerebral av-differences of oxygen and circulating substrates were measured in normocapnic infants during general anaesthesia before elective surgery in order to study possible age-dependent variations. CBF was determined by a minor modification of the Kety-Schmidt technique from desaturation curves of nitrous oxide (N2O) in arterial and cerebral venous blood (N2O analysed by gas chromatography on 15 mul blood samples) after reduction of inhaled N2O from 75 to 50%. The reproducibility was +/-4.6%. Lactate, pyruvate and oxygen were determined in whole blood and amino acids in plasma by ion-exchange chromatography. Reliable av-differences of glucose, acetoacetate and D-beta-hydroxybutyrate could be calculated from plasma values and hematocrits. Mean values from 12 infants (age 11 days-12 months) were: CBF 69 ml/100 g0min-1; cerebral uptake (in mumoles/100 g-min-1): oxygen 104, glucose 27, acetoacetate 0.9, D-beta-hydroxybutyrate 2.3; cerebral release: lactate 2.4 and pyruvate 0.8. Significant uptake of amino acids was found only for histidine 0.95 and arginine 0.7. Significant correlations between arterial concentration and cerebral exchange were found for: ornithine, arginine, phenylalanine, aspartic acid, serine, glutamine and acetoacetate. CBF and substrate exchange were unrelated to age within the group. Infants had higher mean CBF and greater uptake of ketone bodies than has been reported in adults.", "contents": "Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in infants. Cerebral blood flow (CBF) and cerebral av-differences of oxygen and circulating substrates were measured in normocapnic infants during general anaesthesia before elective surgery in order to study possible age-dependent variations. CBF was determined by a minor modification of the Kety-Schmidt technique from desaturation curves of nitrous oxide (N2O) in arterial and cerebral venous blood (N2O analysed by gas chromatography on 15 mul blood samples) after reduction of inhaled N2O from 75 to 50%. The reproducibility was +/-4.6%. Lactate, pyruvate and oxygen were determined in whole blood and amino acids in plasma by ion-exchange chromatography. Reliable av-differences of glucose, acetoacetate and D-beta-hydroxybutyrate could be calculated from plasma values and hematocrits. Mean values from 12 infants (age 11 days-12 months) were: CBF 69 ml/100 g0min-1; cerebral uptake (in mumoles/100 g-min-1): oxygen 104, glucose 27, acetoacetate 0.9, D-beta-hydroxybutyrate 2.3; cerebral release: lactate 2.4 and pyruvate 0.8. Significant uptake of amino acids was found only for histidine 0.95 and arginine 0.7. Significant correlations between arterial concentration and cerebral exchange were found for: ornithine, arginine, phenylalanine, aspartic acid, serine, glutamine and acetoacetate. CBF and substrate exchange were unrelated to age within the group. Infants had higher mean CBF and greater uptake of ketone bodies than has been reported in adults."}
{"id": "PMID:5841", "title": "Down's syndrome with X0/XY mosaicism.", "content": "A 5-month-old Chinese infant with combined Down's syndrome and X0/XY mosaicism is presented. The phenotypical features of mongolism are classical and unmodified. The somatic effects of X0/XY mosaicism is that of incomplete masculinization with short phallus, hypospadias, bifid scrotum, urogenital sinus, and bilateral extra-abdominal infantile testicles. These features together with the absence of internal female organs and signs of Turner's syndrome in this patient are different from the previous reported cases of mixed gonadal dysgenesis.", "contents": "Down's syndrome with X0/XY mosaicism. A 5-month-old Chinese infant with combined Down's syndrome and X0/XY mosaicism is presented. The phenotypical features of mongolism are classical and unmodified. The somatic effects of X0/XY mosaicism is that of incomplete masculinization with short phallus, hypospadias, bifid scrotum, urogenital sinus, and bilateral extra-abdominal infantile testicles. These features together with the absence of internal female organs and signs of Turner's syndrome in this patient are different from the previous reported cases of mixed gonadal dysgenesis."}
{"id": "PMID:5842", "title": "Bile canalicular alkaline phosphatase and disease.", "content": "The alkaline phosphatase reaction is normally absent in human bile canaliculi, but was found in 79 patients. In search for a common causal factor, these patients were further examined. Thirty-seven were autopsied. The conditions most ocmmonly associated with the phenomenon were malignant tumours with or without involvement of the liver, collagen diseases, long-standing partial obstruction of the common bile duct, and genetic variants of alpha-1-antitrypsin. No clinical or laboratory facts were common to all the patients.", "contents": "Bile canalicular alkaline phosphatase and disease. The alkaline phosphatase reaction is normally absent in human bile canaliculi, but was found in 79 patients. In search for a common causal factor, these patients were further examined. Thirty-seven were autopsied. The conditions most ocmmonly associated with the phenomenon were malignant tumours with or without involvement of the liver, collagen diseases, long-standing partial obstruction of the common bile duct, and genetic variants of alpha-1-antitrypsin. No clinical or laboratory facts were common to all the patients."}
{"id": "PMID:5843", "title": "Polyarteritis nodosa associated with nosematosis in blue foxes.", "content": "The patho-morphological lesions in fox nosematosis (encephalitozoonosis) were studied in a material comprising 150 young blue foxes from 23 different farms. Disseminated nosematosis in blue fox pups was regularly accompanied by severe vasculitis, affecting medium-sized and small arteries in various organs. The acute damage has the form of a necrotizing angiitis, with mural necrosis and sometimes resultant thrombosis. The causative organism Nosema cuniculi, is frequently present in the freshly affected arterial walls, either in endothelial or in medial smooth muscle cells. Older lesions include nodular fibrous thickening of the arterial walls, and intimal proliferation, sometimes with luminal obliteration. The conclusion is drawn that the arterial lesions are morphologically equivalent to classical polyarteritis nodosa.", "contents": "Polyarteritis nodosa associated with nosematosis in blue foxes. The patho-morphological lesions in fox nosematosis (encephalitozoonosis) were studied in a material comprising 150 young blue foxes from 23 different farms. Disseminated nosematosis in blue fox pups was regularly accompanied by severe vasculitis, affecting medium-sized and small arteries in various organs. The acute damage has the form of a necrotizing angiitis, with mural necrosis and sometimes resultant thrombosis. The causative organism Nosema cuniculi, is frequently present in the freshly affected arterial walls, either in endothelial or in medial smooth muscle cells. Older lesions include nodular fibrous thickening of the arterial walls, and intimal proliferation, sometimes with luminal obliteration. The conclusion is drawn that the arterial lesions are morphologically equivalent to classical polyarteritis nodosa."}
{"id": "PMID:5844", "title": "Some factors influencing the haemolysis of Bordetella bronchiseptica.", "content": "Strain-dependent variations in the ability of Bordetella bronchiseptica to produce haemolysis on solid media exist. Haemolysis is strongest at an acid reaction and will not take place if the reaction is too alkaline. Peptone and glutamine inhibit haemolysis and favour growth. The vigorous growth rapidly produced an alkaline reaction which inhibits the haemolysis.", "contents": "Some factors influencing the haemolysis of Bordetella bronchiseptica. Strain-dependent variations in the ability of Bordetella bronchiseptica to produce haemolysis on solid media exist. Haemolysis is strongest at an acid reaction and will not take place if the reaction is too alkaline. Peptone and glutamine inhibit haemolysis and favour growth. The vigorous growth rapidly produced an alkaline reaction which inhibits the haemolysis."}
{"id": "PMID:5845", "title": "[Effects of acid-base changes upon the chronotropic response to norepinephrine (author's transl)].", "content": "The effect of changes in pH produced by changing NaHCO2 at constant pCO2 and by changing pCO2 at constant NaHCO2 concentration was studied in the spontaneous beating rat atrium. Alkalosis produced either by changes in pCO2 or in NaHCO2 concentration increased basal heart rate shifting dose-response curves to norepinephrine upwards. When these dose-response curves were analysed for a horizontal shift, it was found that the necessary dose to produce a given effect was lesser in alkalosis than in acidosis. This shift was significant at the ED10 and at ED30 when the pCO2 was lowered and at ED30, ED50 and ED70 when the NaHCO2 concentration was increased. Beta-adrenergic blockade did not prevent the rate increasing effect of alkalosis. Our results suggest that there is a sensitizing effect to norepinephrine in alkalosis superimposed to a direct effect of pH upon heart rate.", "contents": "[Effects of acid-base changes upon the chronotropic response to norepinephrine (author's transl)]. The effect of changes in pH produced by changing NaHCO2 at constant pCO2 and by changing pCO2 at constant NaHCO2 concentration was studied in the spontaneous beating rat atrium. Alkalosis produced either by changes in pCO2 or in NaHCO2 concentration increased basal heart rate shifting dose-response curves to norepinephrine upwards. When these dose-response curves were analysed for a horizontal shift, it was found that the necessary dose to produce a given effect was lesser in alkalosis than in acidosis. This shift was significant at the ED10 and at ED30 when the pCO2 was lowered and at ED30, ED50 and ED70 when the NaHCO2 concentration was increased. Beta-adrenergic blockade did not prevent the rate increasing effect of alkalosis. Our results suggest that there is a sensitizing effect to norepinephrine in alkalosis superimposed to a direct effect of pH upon heart rate."}
{"id": "PMID:5846", "title": "Blood changes in water deprived rats.", "content": "To study the variations of blood constituents during water deprivation, rats were deprived of water from six to twelve days. Control and rehydrated animals were also included in the study. A significant increase was observed in sodium, chloride and hematocrit throughout the experiment. Calcium, bicarbonate and PCO2 increased at 10-11 days of treatment. Potassium, inorganic phosphorus, pH, base excess and blood buffer capacity did not change in the course of the experiment. Rehydrated animals recovered to control levels in all the studied components, except for pH and base excess, which increased somewhat. Plasma volume changes could explain only partially electrolyte variation. The \"dehydration reaction\" is considered to be the main mechanism responsible for these changes. Unchanged hematocrit levels in water deprived animals suggest that after 6 days of water deprivation there is no further loss of plasma water. Bicarbonate and PCO2 changes showed a good relationship and may account for unchanged pH and base excess values.", "contents": "Blood changes in water deprived rats. To study the variations of blood constituents during water deprivation, rats were deprived of water from six to twelve days. Control and rehydrated animals were also included in the study. A significant increase was observed in sodium, chloride and hematocrit throughout the experiment. Calcium, bicarbonate and PCO2 increased at 10-11 days of treatment. Potassium, inorganic phosphorus, pH, base excess and blood buffer capacity did not change in the course of the experiment. Rehydrated animals recovered to control levels in all the studied components, except for pH and base excess, which increased somewhat. Plasma volume changes could explain only partially electrolyte variation. The \"dehydration reaction\" is considered to be the main mechanism responsible for these changes. Unchanged hematocrit levels in water deprived animals suggest that after 6 days of water deprivation there is no further loss of plasma water. Bicarbonate and PCO2 changes showed a good relationship and may account for unchanged pH and base excess values."}
{"id": "PMID:5848", "title": "Effect of ultraviolet radiation on pinocytosis in Amoeba proteua.", "content": "Ultraviolet (UV) irradiation (4 000-10 000 erg X mm(-2) decreased membrane potential and input resistance of Amoeba proteus and induced formation of pinocytotic channels. Submaximal pinocytosis induced by UV light was additive to pinocytosis induced by K+ or Na+ and stimulated in the presence of EGTA. It was not inhibited by the presence of La+++ or by pretreatment with dibucaine. In these respects and with respect to optimum pH and pCa, UV induced pinocytosis. Accumulation of K+ in the amoeba membrane after a dose of radiation may explain the similarity between pinocytosis induced by UV light and potassium salts. Ca++ present during the period of irradiation inhibited the effect of UV light. Instead Ca++ applied after irradiation (1-20 mM) increased channel formation. This effect was stimulated the presence of local anesthetic drugs. It is suggested that high doses of UV light may induce channel formation by releasing Ca++ from the cell membrane into the cell (UV induced pinocytosis). Ca++ may be released at the moment of absorption of UV light in the membrane as well as during the period of depolarization which follows irradiation. Low doses of UV light may permit extracellular Ca++ to enter the cell and stimulate channel formation (calcium induced pinocytosis). Dithiotreitol (1 mM) applied after irradiation depressed both UV and calcium induced pinocytosis so these may be the result of the same structural change which involves the formation of disulphide bonds in the membrane.", "contents": "Effect of ultraviolet radiation on pinocytosis in Amoeba proteua. Ultraviolet (UV) irradiation (4 000-10 000 erg X mm(-2) decreased membrane potential and input resistance of Amoeba proteus and induced formation of pinocytotic channels. Submaximal pinocytosis induced by UV light was additive to pinocytosis induced by K+ or Na+ and stimulated in the presence of EGTA. It was not inhibited by the presence of La+++ or by pretreatment with dibucaine. In these respects and with respect to optimum pH and pCa, UV induced pinocytosis. Accumulation of K+ in the amoeba membrane after a dose of radiation may explain the similarity between pinocytosis induced by UV light and potassium salts. Ca++ present during the period of irradiation inhibited the effect of UV light. Instead Ca++ applied after irradiation (1-20 mM) increased channel formation. This effect was stimulated the presence of local anesthetic drugs. It is suggested that high doses of UV light may induce channel formation by releasing Ca++ from the cell membrane into the cell (UV induced pinocytosis). Ca++ may be released at the moment of absorption of UV light in the membrane as well as during the period of depolarization which follows irradiation. Low doses of UV light may permit extracellular Ca++ to enter the cell and stimulate channel formation (calcium induced pinocytosis). Dithiotreitol (1 mM) applied after irradiation depressed both UV and calcium induced pinocytosis so these may be the result of the same structural change which involves the formation of disulphide bonds in the membrane."}
{"id": "PMID:5849", "title": "An in vitro-formed protamine-heparin complex as a model for a two-compartment store for biogenic amines.", "content": "The capacity of an in vitro-formed protamine-heparin complex (PHC) to store inorganic cations and biogenic amines was investigated. The PHC behaves like a two-compartment storage system. One compartment corresponds to the terminal free carboxyl groups of the protamine moiety and has the characteristics of a cation exchanger, with the ability to bind inorganic cations and biogenic amines in a reversible and rather unslective manner. The cations and biogenic amines therefore compete for and displace each other from the common ionic binding sites. The binding sites in the other compartment, corresponding mainly to the carboxyl groups of the heparin moiety, are only unmasked at high ionic concentrations and show a specific affinity for biogenic amines. The storage of amines in this compartment of the PHC is reversible but is dependent not only on simple ionic binding but evidently also on other attractive forces, such as dipole and hydrogen bonding.", "contents": "An in vitro-formed protamine-heparin complex as a model for a two-compartment store for biogenic amines. The capacity of an in vitro-formed protamine-heparin complex (PHC) to store inorganic cations and biogenic amines was investigated. The PHC behaves like a two-compartment storage system. One compartment corresponds to the terminal free carboxyl groups of the protamine moiety and has the characteristics of a cation exchanger, with the ability to bind inorganic cations and biogenic amines in a reversible and rather unslective manner. The cations and biogenic amines therefore compete for and displace each other from the common ionic binding sites. The binding sites in the other compartment, corresponding mainly to the carboxyl groups of the heparin moiety, are only unmasked at high ionic concentrations and show a specific affinity for biogenic amines. The storage of amines in this compartment of the PHC is reversible but is dependent not only on simple ionic binding but evidently also on other attractive forces, such as dipole and hydrogen bonding."}
{"id": "PMID:5847", "title": "The local effect of pH changes in the cerebrospinal fluid on the ventrolateral areas of medulla oblongata and on the spinal cord surface on the activity of cardiac and vertebral sympathetic nerves.", "content": "Application of acid cerebrospinal fluid at pH 6.8 to the ventral surface of the medulla oblongata in cats increased the arterial blood pressure and the activity of the vertebral nerve and enhanced respiratory modulation of the vertebral and cardiac nerves. Alkaline cerebrospinal fluid at pH 7.7 applied to the ventral surface of the medulla oblongata increased the arterial blood pressure without changes in the sympathetic nerve activity. When the spinal cord was superfussed with artificial acid cerebrospinal fluid at the Th1 level the activity of the vertebral nerve and cardiac nerve increased and the arterial blood pressure rose. The authors discuss the possibility of regulation of the activity of sympathetic neurons in the medulla and spinal cord by means of direct action of pH and pCO2 on the neurons, or through an indirect effect mediated by superficial chemoreceptors of the medulla oblongata. The role of local changes of the brain blood flow in the mechanism of these results is discussed as well.", "contents": "The local effect of pH changes in the cerebrospinal fluid on the ventrolateral areas of medulla oblongata and on the spinal cord surface on the activity of cardiac and vertebral sympathetic nerves. Application of acid cerebrospinal fluid at pH 6.8 to the ventral surface of the medulla oblongata in cats increased the arterial blood pressure and the activity of the vertebral nerve and enhanced respiratory modulation of the vertebral and cardiac nerves. Alkaline cerebrospinal fluid at pH 7.7 applied to the ventral surface of the medulla oblongata increased the arterial blood pressure without changes in the sympathetic nerve activity. When the spinal cord was superfussed with artificial acid cerebrospinal fluid at the Th1 level the activity of the vertebral nerve and cardiac nerve increased and the arterial blood pressure rose. The authors discuss the possibility of regulation of the activity of sympathetic neurons in the medulla and spinal cord by means of direct action of pH and pCO2 on the neurons, or through an indirect effect mediated by superficial chemoreceptors of the medulla oblongata. The role of local changes of the brain blood flow in the mechanism of these results is discussed as well."}
{"id": "PMID:5850", "title": "Oxygen uptake and tissue oxygen tension during adrenergic stimulation in canine subcutaneous adipose tissue.", "content": "The effect of sympathetic nerve stimulation (NS) and injected noradenaline (NA) or isoprenaline (Iso) on PVO2, VO2 and PtO2 was studied in isolated canine subcutaneous adipose tissue. These effects were compared to those produced by mechanical blood flow reduction (clamping). Resting VO2 measured 13.0+/- 2.3 mumol X min-1 X 100 g-1. When blood flow was reduced by 20% or less there was no significant change of VO2. Reducing blood flow to 50% of control or less by NS caused a parallel reduction in VO2, while clamping reduced VO2 significantly less. NA gave effects similar to those of NS. After NS or NA there was a period of hyperemia and increased oxygen extraction which more than compensated for the decrease in VO2 during vasoconstriction. Such a net increase in VO2 was not produced by clamping. Control PtO2 averaged 29+/-2 mmHg. NA reduced it by 70% and clamping to the same blood flow level only by 14% (p less than 0.01). Thus, a mere reduction in blood flow has little effect on PtO2, while blood flow reduction combined with redistribution of blood flow and an increased oxygen deman can lead to tissue hypoxia.", "contents": "Oxygen uptake and tissue oxygen tension during adrenergic stimulation in canine subcutaneous adipose tissue. The effect of sympathetic nerve stimulation (NS) and injected noradenaline (NA) or isoprenaline (Iso) on PVO2, VO2 and PtO2 was studied in isolated canine subcutaneous adipose tissue. These effects were compared to those produced by mechanical blood flow reduction (clamping). Resting VO2 measured 13.0+/- 2.3 mumol X min-1 X 100 g-1. When blood flow was reduced by 20% or less there was no significant change of VO2. Reducing blood flow to 50% of control or less by NS caused a parallel reduction in VO2, while clamping reduced VO2 significantly less. NA gave effects similar to those of NS. After NS or NA there was a period of hyperemia and increased oxygen extraction which more than compensated for the decrease in VO2 during vasoconstriction. Such a net increase in VO2 was not produced by clamping. Control PtO2 averaged 29+/-2 mmHg. NA reduced it by 70% and clamping to the same blood flow level only by 14% (p less than 0.01). Thus, a mere reduction in blood flow has little effect on PtO2, while blood flow reduction combined with redistribution of blood flow and an increased oxygen deman can lead to tissue hypoxia."}
{"id": "PMID:5851", "title": "Beta2-adrenoceptors facilitating noradrenaline secretion from human vasoconstrictor nerves.", "content": "Isolated biopsy specimens of human peripheral arteries and veins, preincubated with 3H-(-)- noradrenaline (NA) to label the neural stores of NA, were used to study the Beta-adrenoceptors previously found to increase the secretion of 3H-NA evoked by electrical field stimulation of the adrenergic nerves of this tissue. The increase in nerve stimulation induced secretion of 3H-NA caused by 0.04 muM isoprenaline was prevented by 1 muM propranolol. This beta-blocking drug by itself slightly but significantly depressed the secretion of 3H-NA caused by nerve stimulation in the absence of isoprenaline. While the secretion of 3H-NA was not affected by known beta1-agonists, it was dose-dependently and reversibly increased by two different beta2-agonists. The effect of isoprenaline on 3H-NA secretion was not altered by a selective beta1-antagonist, but strongly reduced or abolished by a beta2-blocking drug. The results indicate that the beta-adrenoceptors involved in the control of NA secretion from the vasoconstrictor nerves of human omental blood vessels are only to a minimal extent stimulated by NA secreted from the nerves, and therefore do probably not mainly serve to mediate local positive feedback control of transmitter secretion; the receptors appear to be beta2 in nature.", "contents": "Beta2-adrenoceptors facilitating noradrenaline secretion from human vasoconstrictor nerves. Isolated biopsy specimens of human peripheral arteries and veins, preincubated with 3H-(-)- noradrenaline (NA) to label the neural stores of NA, were used to study the Beta-adrenoceptors previously found to increase the secretion of 3H-NA evoked by electrical field stimulation of the adrenergic nerves of this tissue. The increase in nerve stimulation induced secretion of 3H-NA caused by 0.04 muM isoprenaline was prevented by 1 muM propranolol. This beta-blocking drug by itself slightly but significantly depressed the secretion of 3H-NA caused by nerve stimulation in the absence of isoprenaline. While the secretion of 3H-NA was not affected by known beta1-agonists, it was dose-dependently and reversibly increased by two different beta2-agonists. The effect of isoprenaline on 3H-NA secretion was not altered by a selective beta1-antagonist, but strongly reduced or abolished by a beta2-blocking drug. The results indicate that the beta-adrenoceptors involved in the control of NA secretion from the vasoconstrictor nerves of human omental blood vessels are only to a minimal extent stimulated by NA secreted from the nerves, and therefore do probably not mainly serve to mediate local positive feedback control of transmitter secretion; the receptors appear to be beta2 in nature."}
{"id": "PMID:5852", "title": "Vagal reflexes in the bronchoconstriction occurring after induced intravascular platelet aggregation.", "content": "Intravascular platelet aggregation induced in cats by i.v. infusions of collagen caused a transient increase in pulmonary vascular resistance (PVR) and in non-elastic pulmonary resistance (RL), and a transient decrease in dynamic lung compliance (dyn CL). PVR,dyn CL and platelet aggregation after collagen infusions were unaffected by bilateral cervical vagotomy and atropinization, wheras these procedures reduced the post-infusion rise in RL by about 50 per cent. The administration of indomethacin inhibited platelet aggregation as well as bronchoconstriction after collagen infusion. The present investigation indicates that intravascular platelet aggregation will cause reflex bronchoconstriction mediated by vagal efferent fibres.", "contents": "Vagal reflexes in the bronchoconstriction occurring after induced intravascular platelet aggregation. Intravascular platelet aggregation induced in cats by i.v. infusions of collagen caused a transient increase in pulmonary vascular resistance (PVR) and in non-elastic pulmonary resistance (RL), and a transient decrease in dynamic lung compliance (dyn CL). PVR,dyn CL and platelet aggregation after collagen infusions were unaffected by bilateral cervical vagotomy and atropinization, wheras these procedures reduced the post-infusion rise in RL by about 50 per cent. The administration of indomethacin inhibited platelet aggregation as well as bronchoconstriction after collagen infusion. The present investigation indicates that intravascular platelet aggregation will cause reflex bronchoconstriction mediated by vagal efferent fibres."}
{"id": "PMID:5853", "title": "Clinical features in poisonings by tricyclic antidepressants with special reference to the ECG.", "content": "Clinical variables, and especially their relation to the ECG, have been studied in 153 cases of poisonings by tricyclic antidepressants (TCA). The mean age of the patients was 34 years. Amitriptyline poisoning accounted for 112 (73%) of the cases and the mean dose ingested was about 1 000 mg. Coma was present in 87 patients (57%) and on admission 40 (26%) had a systolic blood pressure (BP) below 100 mmHg. The systolic BP on admission was significantly lower (p less than 0.001) and the heart rate (HR) higher (p less than 0.001) than when the patients left the ward. Apart from an increased HR (greater than or equal to 90 beats/min), which was present in 73% of the cases, the most characteristic ECG change was a QRS prolongation (greater than or equal to 0.11 sec), this being found in 42% of the cases. About the same proportion displayed a QT prolongation and 28% had a prolonged PQ time. The mean of the QRS times was 0.11 sec. Unlike the QT time, the QRS time was not correlated to HR. Statistical analysis of the material with regard to clinical variables (dose of TCA, BP, coma duration, etc.) showed that the QRS time was closely related to the severity of poisoning. Five patients (3) died, all of whom already on admission demonstrated advanced ECG changes with arrhythmias and a mean QRS time of 0.19 sec. Excluding dibenzepine poisonings (4 cases, all fatal), the mortality rate was 0.7%. The importance of high initial preparedness for cardiac complications is pointed out, as is the value of the QRS time as a guide to the severity of poisoning.", "contents": "Clinical features in poisonings by tricyclic antidepressants with special reference to the ECG. Clinical variables, and especially their relation to the ECG, have been studied in 153 cases of poisonings by tricyclic antidepressants (TCA). The mean age of the patients was 34 years. Amitriptyline poisoning accounted for 112 (73%) of the cases and the mean dose ingested was about 1 000 mg. Coma was present in 87 patients (57%) and on admission 40 (26%) had a systolic blood pressure (BP) below 100 mmHg. The systolic BP on admission was significantly lower (p less than 0.001) and the heart rate (HR) higher (p less than 0.001) than when the patients left the ward. Apart from an increased HR (greater than or equal to 90 beats/min), which was present in 73% of the cases, the most characteristic ECG change was a QRS prolongation (greater than or equal to 0.11 sec), this being found in 42% of the cases. About the same proportion displayed a QT prolongation and 28% had a prolonged PQ time. The mean of the QRS times was 0.11 sec. Unlike the QT time, the QRS time was not correlated to HR. Statistical analysis of the material with regard to clinical variables (dose of TCA, BP, coma duration, etc.) showed that the QRS time was closely related to the severity of poisoning. Five patients (3) died, all of whom already on admission demonstrated advanced ECG changes with arrhythmias and a mean QRS time of 0.19 sec. Excluding dibenzepine poisonings (4 cases, all fatal), the mortality rate was 0.7%. The importance of high initial preparedness for cardiac complications is pointed out, as is the value of the QRS time as a guide to the severity of poisoning."}
{"id": "PMID:5854", "title": "The mechanism of action of glycosidases.", "content": "The factors that may contribute to the rate enhancement observed with enzymatic versus non-enzymatic hydrolysis of glycosides are discussed. The nature of the active site as deduced from labelling studies with beta-glucosidases is described. A two-step mechanism involving either an enzyme stabilized glycosyl ion or a covalent glycosyl-enzyme intermediate is proposed. Experiments with a beta-glucosidase from almonds show that even with 2-deoxy glucosides with good leaving groups as aglycon which are hydrolyzed 1000 times more slowly than the corresponding glucosides, the deglucosylation step is faster than the cleavage of the glycosidic bond.", "contents": "The mechanism of action of glycosidases. The factors that may contribute to the rate enhancement observed with enzymatic versus non-enzymatic hydrolysis of glycosides are discussed. The nature of the active site as deduced from labelling studies with beta-glucosidases is described. A two-step mechanism involving either an enzyme stabilized glycosyl ion or a covalent glycosyl-enzyme intermediate is proposed. Experiments with a beta-glucosidase from almonds show that even with 2-deoxy glucosides with good leaving groups as aglycon which are hydrolyzed 1000 times more slowly than the corresponding glucosides, the deglucosylation step is faster than the cleavage of the glycosidic bond."}
{"id": "PMID:5855", "title": "Properties of hydroxysteroid oxidoreductase isolated from yeast.", "content": "Yeasts can advantageously be utilized for the production of the 17beta-hydroxy-derivative, from 3-methoxy-8,14-seco-1,3,5(10),9(11)-estratetraene-14,17-dione (14,17-dione) while 14alpha-hydroxy and 14alpha,17beta-dihydroxy-derivatives are also formed. The biochemical properties of yeasts' enzymes responsible for the formation of the two monohydroxy-derivatives have been studied in detail. In the cell-free extract of Saccharomyces the presence of two hydroxysteroid oxidoreductases could be detected. The first enzyme forms 3beta,17beta-dihydroxy-derivative from 5alpha-androstane-317-dione. This enzyme is responsible for the formation of 17beta-hydroxy-derivative from 14,17-dione. The second enzyme forms 3alpha-hydroxy-derivative from 5beta-androstanedione as well as 14alpha-hydroxy-derivative from its 14,17-dione. The cofactor of both enzymes is pyridine nucleotide. The two enzymes possessing different properties can selectively be inhibited.", "contents": "Properties of hydroxysteroid oxidoreductase isolated from yeast. Yeasts can advantageously be utilized for the production of the 17beta-hydroxy-derivative, from 3-methoxy-8,14-seco-1,3,5(10),9(11)-estratetraene-14,17-dione (14,17-dione) while 14alpha-hydroxy and 14alpha,17beta-dihydroxy-derivatives are also formed. The biochemical properties of yeasts' enzymes responsible for the formation of the two monohydroxy-derivatives have been studied in detail. In the cell-free extract of Saccharomyces the presence of two hydroxysteroid oxidoreductases could be detected. The first enzyme forms 3beta,17beta-dihydroxy-derivative from 5alpha-androstane-317-dione. This enzyme is responsible for the formation of 17beta-hydroxy-derivative from 14,17-dione. The second enzyme forms 3alpha-hydroxy-derivative from 5beta-androstanedione as well as 14alpha-hydroxy-derivative from its 14,17-dione. The cofactor of both enzymes is pyridine nucleotide. The two enzymes possessing different properties can selectively be inhibited."}
{"id": "PMID:5856", "title": "Properties of delta5-3beta-hydroxysteroid oxidoreductase isolated from Streptomyces griseocarneus.", "content": "Delta5-3beta-hydroxysteroid oxidoreductase was extracted in magnesium-containing Tris buffer from sonicated Streptomyces griseocarneus cells. The enzyme was partially purified (150 X) by ion exchange chromatography and gel filtration following (NH4)2SO4 fractionation. Upon gel filtration on Sephadex G-75 to G-200, the greatest part of the activity gave a peak in the fractionation range. The enzyme obtained from the gel yielded small enzyme molecules on repeated chromatography. A molecular weight of 32 to 36 000 was calculated for the activity appearing in the fractionation range of Sephadex G-75 to G-200. The enzyme is highly specific for the irreversible oxidation of the 3beta-hydroxyl group in steroids with a trans-anellated A : B ring system with either C5 or C6 double bond. Delta5-3-ketosteroids are converted into delta5-3-ketosteroids at a high rate, but the isomerase activity cannot be separated from the oxidoreductase activity either by chromatography or by selective heat inactivation. NAD, NADP, FMN or FAD did not influence the activity, but the enzyme is inactive in the absence of molecular oxygen.", "contents": "Properties of delta5-3beta-hydroxysteroid oxidoreductase isolated from Streptomyces griseocarneus. Delta5-3beta-hydroxysteroid oxidoreductase was extracted in magnesium-containing Tris buffer from sonicated Streptomyces griseocarneus cells. The enzyme was partially purified (150 X) by ion exchange chromatography and gel filtration following (NH4)2SO4 fractionation. Upon gel filtration on Sephadex G-75 to G-200, the greatest part of the activity gave a peak in the fractionation range. The enzyme obtained from the gel yielded small enzyme molecules on repeated chromatography. A molecular weight of 32 to 36 000 was calculated for the activity appearing in the fractionation range of Sephadex G-75 to G-200. The enzyme is highly specific for the irreversible oxidation of the 3beta-hydroxyl group in steroids with a trans-anellated A : B ring system with either C5 or C6 double bond. Delta5-3-ketosteroids are converted into delta5-3-ketosteroids at a high rate, but the isomerase activity cannot be separated from the oxidoreductase activity either by chromatography or by selective heat inactivation. NAD, NADP, FMN or FAD did not influence the activity, but the enzyme is inactive in the absence of molecular oxygen."}
{"id": "PMID:5857", "title": "Soil microflora of the rhizosphere of plants from several habitats in the botanical garden in Pozna\u0144.", "content": "The abundance and activity of certain groups of soil microorganisms were estimated in the rhizosphere of 13 plants from four different habitats at several dates. An additional study was made of the rhizosphere microflora of Ledum palustre from a peat-bog. Numbers of proteolytic, nitrate assimilating, denitrifying, and cellulolytic bacteria were estimated. The intensity of ammonification, nitrification and Clostridium growth was estimated. The studies have revealed that the abundance and the activity of all the groups of bacteria studied depended on the habitat. Within one habitat, however, the influence of the plant was sometimes more pronounced than that of the habitat itself, particularly on the abundance of proteolytic bacteria (Fig. 1). The date of sampling had very little effect on the abundance of all the bacterial groups studied except the cellulolytic bacteria.", "contents": "Soil microflora of the rhizosphere of plants from several habitats in the botanical garden in Pozna\u0144. The abundance and activity of certain groups of soil microorganisms were estimated in the rhizosphere of 13 plants from four different habitats at several dates. An additional study was made of the rhizosphere microflora of Ledum palustre from a peat-bog. Numbers of proteolytic, nitrate assimilating, denitrifying, and cellulolytic bacteria were estimated. The intensity of ammonification, nitrification and Clostridium growth was estimated. The studies have revealed that the abundance and the activity of all the groups of bacteria studied depended on the habitat. Within one habitat, however, the influence of the plant was sometimes more pronounced than that of the habitat itself, particularly on the abundance of proteolytic bacteria (Fig. 1). The date of sampling had very little effect on the abundance of all the bacterial groups studied except the cellulolytic bacteria."}
{"id": "PMID:5858", "title": "Kinetic studies on citric acid production by Aspergillus niger. II. The two-stage process.", "content": "A two-stage process of submerged citric acid fermentation with replacement of growth medium by fermentation medium has been worked out. The optimum composition of mineral nutrients and pH of the fermentation medium of the second stage of the process were determined. An addition of 0.5 g/l of NH4NO3 as nitrogen source and 0.1 g/l of MgSO4-7H2O as magnesium source ensured effective conversion of sucrose to citric acid. An addition to KH2PO4, on the other hand, was definitely unfavourable as it considerably reduced the product yield. The medium for the second stage of fermentation should be acidified to about pH 2.2, while the water used for washing the mycelium from the remains of the growth medium should have a pH of 2.5--3.5. Under these conditions, with an initial sucrose concentration of 100 g/l, after 132 hr fermentation at 26 degrees up to 90 g/l of citric acid was obtained, which corresponds to a productivity of over 16 g/l. day. The highest activity for citric acid formation was found in three- or four-day-old mycelium.", "contents": "Kinetic studies on citric acid production by Aspergillus niger. II. The two-stage process. A two-stage process of submerged citric acid fermentation with replacement of growth medium by fermentation medium has been worked out. The optimum composition of mineral nutrients and pH of the fermentation medium of the second stage of the process were determined. An addition of 0.5 g/l of NH4NO3 as nitrogen source and 0.1 g/l of MgSO4-7H2O as magnesium source ensured effective conversion of sucrose to citric acid. An addition to KH2PO4, on the other hand, was definitely unfavourable as it considerably reduced the product yield. The medium for the second stage of fermentation should be acidified to about pH 2.2, while the water used for washing the mycelium from the remains of the growth medium should have a pH of 2.5--3.5. Under these conditions, with an initial sucrose concentration of 100 g/l, after 132 hr fermentation at 26 degrees up to 90 g/l of citric acid was obtained, which corresponds to a productivity of over 16 g/l. day. The highest activity for citric acid formation was found in three- or four-day-old mycelium."}
{"id": "PMID:5859", "title": "L-Glutamate-glyoxylate aminotransferase in Lactobacillus plantarum.", "content": "Glutamate-glyoxylate aminotransferase which mediates the reaction of glyoxylic acid with glutamic acid to yield glycine and alpha-oxoglutaric acid has been isolated and purified 84-fold from extracts of Lactobacillus plantarum. Purified enzyme requires the addition of pyridoxal phosphate and magnesium ions for its activity. The molecular weight of the enzyme estimated by Sepharose 4B gel filtration amounts to 37.000. Micaelis constants for glyoxylate and glutamate are corresponding to 6.25 X 10(-3) M and 2.75 X 10(-3) M, respectively. Optimal pH in phosphate and veronal buffers is 8.0 and optimal temperature 35--37 degrees C.", "contents": "L-Glutamate-glyoxylate aminotransferase in Lactobacillus plantarum. Glutamate-glyoxylate aminotransferase which mediates the reaction of glyoxylic acid with glutamic acid to yield glycine and alpha-oxoglutaric acid has been isolated and purified 84-fold from extracts of Lactobacillus plantarum. Purified enzyme requires the addition of pyridoxal phosphate and magnesium ions for its activity. The molecular weight of the enzyme estimated by Sepharose 4B gel filtration amounts to 37.000. Micaelis constants for glyoxylate and glutamate are corresponding to 6.25 X 10(-3) M and 2.75 X 10(-3) M, respectively. Optimal pH in phosphate and veronal buffers is 8.0 and optimal temperature 35--37 degrees C."}
{"id": "PMID:5863", "title": "Inhibition of Newcastle disease virus replication by 6-azauridine. II. Combination of 6-azauridine and adenine derivatives.", "content": "Twenty-five metabolites (purines, pyrimidines, nucleosides and nucleosides) were tested for their simultaneous action with 6-azauridine (AzUrd) in inhibition of Newcastle disease virus (NDV) replication. With the exception of deoxyadenosine and cyclic AMP all natural adenine derivatives exerted a synergic effect with AzUrd like ATP. Glutamine in combination with AzUrd did not inhibit NDV replication. The inhibitory effect of the combination of AzUrd and adenine derivatives was reversible by guanosine, uridine and cytidine but not by orotic acid or orotidylic acid.", "contents": "Inhibition of Newcastle disease virus replication by 6-azauridine. II. Combination of 6-azauridine and adenine derivatives. Twenty-five metabolites (purines, pyrimidines, nucleosides and nucleosides) were tested for their simultaneous action with 6-azauridine (AzUrd) in inhibition of Newcastle disease virus (NDV) replication. With the exception of deoxyadenosine and cyclic AMP all natural adenine derivatives exerted a synergic effect with AzUrd like ATP. Glutamine in combination with AzUrd did not inhibit NDV replication. The inhibitory effect of the combination of AzUrd and adenine derivatives was reversible by guanosine, uridine and cytidine but not by orotic acid or orotidylic acid."}
{"id": "PMID:5864", "title": "Some biological activities of rabbit anti-interferon serum.", "content": "After prolonged immunization of rabbits with a semipurified mouse interferon preparation in Freund's incomplete or Al-Span-Oil adjuvant, a specific interferon-neutralizing immunoglobulin was obtained from antiserum with a capacity of neutralizing about 49000 mouse interferon units per ml. The specific activity of the antiserum and immunoglobulin was confirmed in tests in which the interaction of antibodies with the cell surface was ruled out. The antiserum (and the immunoglobulin) neutralized both the antiviral and the cell-growth inhibitory activities of interferon. The \"slow\" and the \"fast\" fractions of purified interferon preparations were equally sensitive to the neutralizing effect of antibodies. On the other hand, the reaction of heat-inactivated interferon with the antiserum did not diminish the neutralizing activity of the latter, suggesting a destruction of interferon antigenic sites.", "contents": "Some biological activities of rabbit anti-interferon serum. After prolonged immunization of rabbits with a semipurified mouse interferon preparation in Freund's incomplete or Al-Span-Oil adjuvant, a specific interferon-neutralizing immunoglobulin was obtained from antiserum with a capacity of neutralizing about 49000 mouse interferon units per ml. The specific activity of the antiserum and immunoglobulin was confirmed in tests in which the interaction of antibodies with the cell surface was ruled out. The antiserum (and the immunoglobulin) neutralized both the antiviral and the cell-growth inhibitory activities of interferon. The \"slow\" and the \"fast\" fractions of purified interferon preparations were equally sensitive to the neutralizing effect of antibodies. On the other hand, the reaction of heat-inactivated interferon with the antiserum did not diminish the neutralizing activity of the latter, suggesting a destruction of interferon antigenic sites."}
{"id": "PMID:5865", "title": "Interferon-producing capacity of human tonsil cells and properties of interferon produced by these cells.", "content": "Tonsils excised from human beings for chronic tonsillitis have been shown to be an accessible and sufficiently rich source of human lymphocytes. Tonsil cells produced interferon as intensively as blood leukocytes and the properties of this interferon were similar to those of leukocyte interferon. The optimal conditions for interferon production by tonsil cells were established.", "contents": "Interferon-producing capacity of human tonsil cells and properties of interferon produced by these cells. Tonsils excised from human beings for chronic tonsillitis have been shown to be an accessible and sufficiently rich source of human lymphocytes. Tonsil cells produced interferon as intensively as blood leukocytes and the properties of this interferon were similar to those of leukocyte interferon. The optimal conditions for interferon production by tonsil cells were established."}
{"id": "PMID:5866", "title": "Diminished virucidal activity of kethoxal against vesicular stomatitis virus pretreated with guanidinating reagent and proteases.", "content": "The reactivity of vesicular stomatitis virus (VSV) with kethoxal can be appreciably altered by treatment with 1-guanyl-3, 5-dimethyl pyrazole nitrate (GDMP) and proteolytic enzymes. Pretreatment of purified VSV with GDMP or proteolytic enzymes markedly reduced the effectiveness of kethoxal as a virucide. The rate of neutralizability of GDMP- and trypsin-treated viruses by specific antiserum differed from that of controls.", "contents": "Diminished virucidal activity of kethoxal against vesicular stomatitis virus pretreated with guanidinating reagent and proteases. The reactivity of vesicular stomatitis virus (VSV) with kethoxal can be appreciably altered by treatment with 1-guanyl-3, 5-dimethyl pyrazole nitrate (GDMP) and proteolytic enzymes. Pretreatment of purified VSV with GDMP or proteolytic enzymes markedly reduced the effectiveness of kethoxal as a virucide. The rate of neutralizability of GDMP- and trypsin-treated viruses by specific antiserum differed from that of controls."}
{"id": "PMID:5867", "title": "Levels of immunoglobulins and antibodies to haemaglutinin and neuraminidase of influenza virus in nasal secretions after natural infection.", "content": "Nasal washings (NW) from 16 influenza patients in the course of an epidemic in November and December, 1974 were examined for the presence of influenza virus, immunoglobulins (Ig) and titres of haemagglutination inhibiting (HI) and neuraminidase inhibiting (NI) antibodies. Influenza virus identical with A/Port Chalmers/1/73 (H3N2), increased levels of IgA and occasionally IgG, and specific antibodies were detected in the NW. The dynamics of HI and NI antibody formation did not differ substantially, but there were individual differences in titres and persistence of antibodies. Convalescent sera always contained increased levels of HI and NI antibodies. In some cases, the titres of antibody to viral ribonucleoprotein did not increase.", "contents": "Levels of immunoglobulins and antibodies to haemaglutinin and neuraminidase of influenza virus in nasal secretions after natural infection. Nasal washings (NW) from 16 influenza patients in the course of an epidemic in November and December, 1974 were examined for the presence of influenza virus, immunoglobulins (Ig) and titres of haemagglutination inhibiting (HI) and neuraminidase inhibiting (NI) antibodies. Influenza virus identical with A/Port Chalmers/1/73 (H3N2), increased levels of IgA and occasionally IgG, and specific antibodies were detected in the NW. The dynamics of HI and NI antibody formation did not differ substantially, but there were individual differences in titres and persistence of antibodies. Convalescent sera always contained increased levels of HI and NI antibodies. In some cases, the titres of antibody to viral ribonucleoprotein did not increase."}
{"id": "PMID:5868", "title": "Associated seroconversions to respiratory viruses in volunteers with experimental influenza infection.", "content": "Serological examinations of 573 volunteers with mild experimental influenza infection and 86 volunteers of a control group hospitalized in a special clinic revealed a significant rise in the titre of antibodies (seroconversion) not only to influenza A or B viruses used for the experimental infection but in 23.3 to 29.8% of cases also to other respiratory viruses. Based on a number of arguments, associated seroconversions are interpreted as due to mixed or sequential infections of different aetiology.", "contents": "Associated seroconversions to respiratory viruses in volunteers with experimental influenza infection. Serological examinations of 573 volunteers with mild experimental influenza infection and 86 volunteers of a control group hospitalized in a special clinic revealed a significant rise in the titre of antibodies (seroconversion) not only to influenza A or B viruses used for the experimental infection but in 23.3 to 29.8% of cases also to other respiratory viruses. Based on a number of arguments, associated seroconversions are interpreted as due to mixed or sequential infections of different aetiology."}
{"id": "PMID:5869", "title": "Different allotypic susceptibility of mice to Rickett-sia tsutsugamushi.", "content": "Some lines of mice and random-bred mice show different susceptibility to infection with Rickettsia tsutsugamushi, displayed mainly in the development of overt infection. The latter is most markedly manifested in random-bred and Swiss mice, causing high death rates and massive accumulation of rickettsiae in the peritoneum. Black mice respond to inoculation with asymptomatic infection with no microscopically detectable rickettsiae. The infection is accompanied in either case by immunological response and persistence of the agent in mice. One of the mechanisms of resistance to R. tsutsugamushi in some mouse lines is due to phagocytosis at the inoculation site of the main mass of rickettsiae by macrophages which digest the agent and retain their viability.", "contents": "Different allotypic susceptibility of mice to Rickett-sia tsutsugamushi. Some lines of mice and random-bred mice show different susceptibility to infection with Rickettsia tsutsugamushi, displayed mainly in the development of overt infection. The latter is most markedly manifested in random-bred and Swiss mice, causing high death rates and massive accumulation of rickettsiae in the peritoneum. Black mice respond to inoculation with asymptomatic infection with no microscopically detectable rickettsiae. The infection is accompanied in either case by immunological response and persistence of the agent in mice. One of the mechanisms of resistance to R. tsutsugamushi in some mouse lines is due to phagocytosis at the inoculation site of the main mass of rickettsiae by macrophages which digest the agent and retain their viability."}
{"id": "PMID:5870", "title": "Cytological investigation of Rickettsia tsutsugamushi infection of mice with different allotypic susceptibility to the agent.", "content": "Cytological and cytochemical studies on Swiss and random-bred white mice susceptible to Rickettsia tsutsugamushi infection as well as resistant C57 Black 6 and CBA mice revealed a clear-cut relationship between the severity of infection and the pattern of macrophage reaction. In highly susceptible mice the fatal infection was accompanied by death of macrophages and necrotisation of the peritoneal exudate cells. The resistant mice showed no clinical signs but developed an intensive macrophage reaction, and the main mass of the inoculated rickettsiae died at the inoculation site, the macrophages remaining viable. Phagocytosis and digestion of rickettsiae were accompanied by markedly increased activities of hydrolytic and oxidizing-reducing enzymes.", "contents": "Cytological investigation of Rickettsia tsutsugamushi infection of mice with different allotypic susceptibility to the agent. Cytological and cytochemical studies on Swiss and random-bred white mice susceptible to Rickettsia tsutsugamushi infection as well as resistant C57 Black 6 and CBA mice revealed a clear-cut relationship between the severity of infection and the pattern of macrophage reaction. In highly susceptible mice the fatal infection was accompanied by death of macrophages and necrotisation of the peritoneal exudate cells. The resistant mice showed no clinical signs but developed an intensive macrophage reaction, and the main mass of the inoculated rickettsiae died at the inoculation site, the macrophages remaining viable. Phagocytosis and digestion of rickettsiae were accompanied by markedly increased activities of hydrolytic and oxidizing-reducing enzymes."}
{"id": "PMID:5871", "title": "Characterization of an endotoxic lipopolysaccharide from Coxiella burnetii.", "content": "Phase I Coxiella burnetii antigen isolated by phenol extraction from purified suspensions of C. burnetii in phase I is a complex lipopolysaccharide (LPS) molecule containing substances typical of the bacterial LPS. Some endotoxic properties of this C. burnetii LPS, namely pyrogenicity and skin epinephrine reaction in rabbits, hypothermia in white rats, lethal effect on chicken embryos or on actinomycin-D-treated mice are similar to those of LPS isolated from other Gram-negative bacteria.", "contents": "Characterization of an endotoxic lipopolysaccharide from Coxiella burnetii. Phase I Coxiella burnetii antigen isolated by phenol extraction from purified suspensions of C. burnetii in phase I is a complex lipopolysaccharide (LPS) molecule containing substances typical of the bacterial LPS. Some endotoxic properties of this C. burnetii LPS, namely pyrogenicity and skin epinephrine reaction in rabbits, hypothermia in white rats, lethal effect on chicken embryos or on actinomycin-D-treated mice are similar to those of LPS isolated from other Gram-negative bacteria."}
{"id": "PMID:5872", "title": "Electron microscopy of virus particles in ultrathin frozen sections.", "content": "A procedure with the use of polyethylene glycol (PEG) 600 to support biological materials for ultracryotomy was developed. Developing and mature virions were demonstrated by electron microscopy in negatively stained frozen sections of vaccinia virus-infected human diploid cells and of herpes simplex virus (HSV) type 1 infected primary rabbit kidney cells. Approximate localisation of the virus particles in the cells was possible.", "contents": "Electron microscopy of virus particles in ultrathin frozen sections. A procedure with the use of polyethylene glycol (PEG) 600 to support biological materials for ultracryotomy was developed. Developing and mature virions were demonstrated by electron microscopy in negatively stained frozen sections of vaccinia virus-infected human diploid cells and of herpes simplex virus (HSV) type 1 infected primary rabbit kidney cells. Approximate localisation of the virus particles in the cells was possible."}
{"id": "PMID:5873", "title": "Interferon pretreatment primes interferon production by human adenovirus in chick embryo cells.", "content": "Pretreatment of chick embryo cells (CEC) with homologous interferon enhanced the subsequent interferon production induced by human adenovirus. This priming effect of interferon pretreatment was also demonstrable when trypsin-treated virus was used for the induction of interferon.", "contents": "Interferon pretreatment primes interferon production by human adenovirus in chick embryo cells. Pretreatment of chick embryo cells (CEC) with homologous interferon enhanced the subsequent interferon production induced by human adenovirus. This priming effect of interferon pretreatment was also demonstrable when trypsin-treated virus was used for the induction of interferon."}
{"id": "PMID:5874", "title": "Enhancement of interferon induction in mice by polycationic modified polypeptides.", "content": "Combined intraperitoneal treatment of mice with poly I: C and a polycationic modified polypeptide (poly-DMAE-glutamine) was investigated. It was established that the presence of appropriate amounts of poly-DMAE-glutamine produced markedly enhanced serum interferon levels as compared to those produced by poly I: C alone. Similar combinations injected into mice produced full protection against lethal doses of mouse-virulent Semliki forest virus.", "contents": "Enhancement of interferon induction in mice by polycationic modified polypeptides. Combined intraperitoneal treatment of mice with poly I: C and a polycationic modified polypeptide (poly-DMAE-glutamine) was investigated. It was established that the presence of appropriate amounts of poly-DMAE-glutamine produced markedly enhanced serum interferon levels as compared to those produced by poly I: C alone. Similar combinations injected into mice produced full protection against lethal doses of mouse-virulent Semliki forest virus."}
{"id": "PMID:5878", "title": "Inhibition of Newcastle disease virus replication by 6-azauridine. I. Inefficacy of purified uridine kinase, effect of adenosine-5'-triphosphate.", "content": "As distinct from cell-free extracts prepared from tumour cells, partially purified uridine kinase prepared from the same cells was not effective in 6-azauridine (AzUrd) inhibition of Newcastle disease virus (NDV) replication. This showed that uridine kinase was not the effective component of cell-free extracts. Adenosine-5'-triphosphate (ATP) was found to exert a synergic effect in combination with AzUrd in the inhibition of NDV replication.", "contents": "Inhibition of Newcastle disease virus replication by 6-azauridine. I. Inefficacy of purified uridine kinase, effect of adenosine-5'-triphosphate. As distinct from cell-free extracts prepared from tumour cells, partially purified uridine kinase prepared from the same cells was not effective in 6-azauridine (AzUrd) inhibition of Newcastle disease virus (NDV) replication. This showed that uridine kinase was not the effective component of cell-free extracts. Adenosine-5'-triphosphate (ATP) was found to exert a synergic effect in combination with AzUrd in the inhibition of NDV replication."}
{"id": "PMID:5880", "title": "Effect of vagus nerve stimulation upon excitability of the canine ventricle. Role of sympathetic-parasympathetic interactions.", "content": "The effect of vagus nerve stimulation on ventricular excitability was studied in 28 dogs under various conditions of adrenergic neural tone. Strength-interval curves were delineated from the apex of the right ventricular endocardium with a transvenous bipolar catheter. Vagus nerve stimulation in both closed chest and open chest dogs shifted the strength-interval curve 6 to 8 msec later into electrical diastole (P less than 0.001). Left stellate ganglion stimulation shifted the strength-interval curve 9 to 11 msec earlier into diastole (P less than 0.001). The effect of simultaneous left stellate ganglion and vagus nerve stimulation was not significantly different from that of left stellate ganglion stimulation alone. The influence of vagus nerve stimulation on the strength-interval curve under basal conditions was abolished by acute beta adrenergic blockade with propranolol. It is concluded that vagus nerve stimulation affects ventricular excitability as well as vulnerability by opposing the effects of sympathetic neural tone.", "contents": "Effect of vagus nerve stimulation upon excitability of the canine ventricle. Role of sympathetic-parasympathetic interactions. The effect of vagus nerve stimulation on ventricular excitability was studied in 28 dogs under various conditions of adrenergic neural tone. Strength-interval curves were delineated from the apex of the right ventricular endocardium with a transvenous bipolar catheter. Vagus nerve stimulation in both closed chest and open chest dogs shifted the strength-interval curve 6 to 8 msec later into electrical diastole (P less than 0.001). Left stellate ganglion stimulation shifted the strength-interval curve 9 to 11 msec earlier into diastole (P less than 0.001). The effect of simultaneous left stellate ganglion and vagus nerve stimulation was not significantly different from that of left stellate ganglion stimulation alone. The influence of vagus nerve stimulation on the strength-interval curve under basal conditions was abolished by acute beta adrenergic blockade with propranolol. It is concluded that vagus nerve stimulation affects ventricular excitability as well as vulnerability by opposing the effects of sympathetic neural tone."}
{"id": "PMID:5881", "title": "An automated flavin adenine dinucleotide-dependent glutathione reductase assay for assessing riboflavin nutriture.", "content": "An automated AutoAnalyzer method using 5:5'-dithiobis-2-nitrobenzoic acid is described for determining whole blood glutathione reductase (BGR) activity and for measuring in vitro activation of BGR with flavin adenine dinucleotide (FAD). BGR activity is expressed as mumoles glutathione regenerated from oxidized glutathione per ml of whole blood (WB) or per g of hemoglobin. The stimulatory effect of FAD on BGR activity divided by the activity without FAD determined the activity coefficient (AC). We found that NADPH and oxidized glutathione assay concentrations of 0.100 mmole/liter and 0.250 mmole/liter, respectively, in 0.1 mole/liter phosphate buffer, pH 7.4, gave consistent results when WB, before assay, was diluted 20-fold. WB samples to be stored are initially diluted 10-fold with distilled water and frozen. Prior to assay, two aliquots of the sample are diluted 2-fold, one aliquot with distilled water and another with 46 mumole/liter FAD. With sample and manifold dilutions the assay FAD concentrations is 1.0 mumole/liter: assay concentrations greater than 5.0 mumole FAD/liter were shown to be inhibitory. We examined blood samples from 617 children in the age range 6 to 60 months and determined the normal AC range to be between 1.00 and 1.35. Six weaned rats (23 days of age), maintained on a riboflavin-deficient diet, showed a mean AC of 1.23, 1.54, 2.02, and 2.41 at 23, 26, 30, and 36 days of age, respectively. Six control rats maintained an AC of 1.23 +/- 0.05 (SD) during the same period.", "contents": "An automated flavin adenine dinucleotide-dependent glutathione reductase assay for assessing riboflavin nutriture. An automated AutoAnalyzer method using 5:5'-dithiobis-2-nitrobenzoic acid is described for determining whole blood glutathione reductase (BGR) activity and for measuring in vitro activation of BGR with flavin adenine dinucleotide (FAD). BGR activity is expressed as mumoles glutathione regenerated from oxidized glutathione per ml of whole blood (WB) or per g of hemoglobin. The stimulatory effect of FAD on BGR activity divided by the activity without FAD determined the activity coefficient (AC). We found that NADPH and oxidized glutathione assay concentrations of 0.100 mmole/liter and 0.250 mmole/liter, respectively, in 0.1 mole/liter phosphate buffer, pH 7.4, gave consistent results when WB, before assay, was diluted 20-fold. WB samples to be stored are initially diluted 10-fold with distilled water and frozen. Prior to assay, two aliquots of the sample are diluted 2-fold, one aliquot with distilled water and another with 46 mumole/liter FAD. With sample and manifold dilutions the assay FAD concentrations is 1.0 mumole/liter: assay concentrations greater than 5.0 mumole FAD/liter were shown to be inhibitory. We examined blood samples from 617 children in the age range 6 to 60 months and determined the normal AC range to be between 1.00 and 1.35. Six weaned rats (23 days of age), maintained on a riboflavin-deficient diet, showed a mean AC of 1.23, 1.54, 2.02, and 2.41 at 23, 26, 30, and 36 days of age, respectively. Six control rats maintained an AC of 1.23 +/- 0.05 (SD) during the same period."}
{"id": "PMID:5882", "title": "Accidental poisoning with psychotropic drugs in children.", "content": "Seventy-seven (0.24%) of 32,005 admissions to the Massachusetts General Hospital pediatric service during the period 1962 to 1973 were due to accidental poisoning. In 27 cases, mostly involving children less than 6 years of age, psychotropic drugs were implicated. These included sedative-hypnotics in six cases, phenytoin in two, major tranquilizers in five, antidepressants in three, stimulants or hallucinogens in three, and drug mixtures in eight. Toxicologic analyses contributed little to diagnosis and initial management. Except for one child who ingested ferrous sulfate, no patient was seriously intoxicated, and all recovered rapidly without sequelae. Although referral of serious poisoning cases to another hospital may have biased the results, the findings suggest that accidental psychotropic drug poisoning is not a major source of childhood morbidity.", "contents": "Accidental poisoning with psychotropic drugs in children. Seventy-seven (0.24%) of 32,005 admissions to the Massachusetts General Hospital pediatric service during the period 1962 to 1973 were due to accidental poisoning. In 27 cases, mostly involving children less than 6 years of age, psychotropic drugs were implicated. These included sedative-hypnotics in six cases, phenytoin in two, major tranquilizers in five, antidepressants in three, stimulants or hallucinogens in three, and drug mixtures in eight. Toxicologic analyses contributed little to diagnosis and initial management. Except for one child who ingested ferrous sulfate, no patient was seriously intoxicated, and all recovered rapidly without sequelae. Although referral of serious poisoning cases to another hospital may have biased the results, the findings suggest that accidental psychotropic drug poisoning is not a major source of childhood morbidity."}
{"id": "PMID:5879", "title": "[Mediators of the allergic reaction. Slow reacting substance (SRS-A)].", "content": "The slow reacting substance of anaphylaxis (SRS-A) belongs to a group of substances which produce a slow progressive and sustained contraction of some smooth muscles. It is released by the interaction of the antigen with certain antibodies; in humans through the interaction with the IgE or reagine. The SRS-A is a heat-labile sustance, chemically unstable, of an acid character, with a low molecular weight. It is not destroyed by the action of proteolytic enzymes. Its molecular structure has not yet been elucidated. It is not found accumulated in the cells but synthesized and released by some white cells mainly by sensitized mast cells and polymorphonuclear leukocytes after challenging with the specific antigen. The SRS-A is a powerful pharmacodynamic agent, it produces contraction of the bronchial smooth muscle in doses of nanograms. It probably plays a predominant role in the physiopathology of asthma. The chain of chemical reactions elicited by antigen-antibody interaction does not end with the release of SRS-A and the other mediators (histamine, eosinophil chemotactic factor of anaphylaxis, ECF-A), on the contrary, these mediators especially SRS-A induce the release of prostaglandins of type E (PGE1 and PGE2) which produce bronchodilatation and inhibit the release of SRS-A itself, perhaps being a selfregulating mechanism. The PGF2a, on the other hand, produces bronchoconstriction. The release of SRS-A is also inhibited by the action of diethyl-carbamazine and especially by sodium chromoglicate and compound AH-7725. From the biochemical point of view it is found that the antigen Igells, a serine esterase, initiating several chemical reactions whose consequence is a decrease in the cAMP concentration. This reduction in the cAMP intracellular level is followed by synthesis and excretion of the SRS-A as well as by the aggregation of the microtubules and excretion of the stored histamine. The PGE (1 and 2) acting on one type of membrane receptor and the beta-agonist catecholamines on another produce a common phenomenon: the activation of the adenylcyclase whcih produces the increase of the concentration of cAMP and inhibits the release of mediators of the anapylactic reaction. The parasympathetic system through its chemical mediator acethylcholine, by a mechanism in whcih adenycyclase is not involved is also capable of stimulating the release of histamine and SRS-A. Something similar happens with PGF2a. In conclusion, self-regulatory mechansims for the release of mediators of the anaphylactic reactions may exist. The \"perpetuation\" of an asthamtic reaction would signify a failure of these self-regulatory mechanisms due to, for example, to a temporary block of the beta-adrenergic receptors, overstimulation of the alfa-receptors or insufficient production of PGE or a transformation of the PGE in PGF.", "contents": "[Mediators of the allergic reaction. Slow reacting substance (SRS-A)]. The slow reacting substance of anaphylaxis (SRS-A) belongs to a group of substances which produce a slow progressive and sustained contraction of some smooth muscles. It is released by the interaction of the antigen with certain antibodies; in humans through the interaction with the IgE or reagine. The SRS-A is a heat-labile sustance, chemically unstable, of an acid character, with a low molecular weight. It is not destroyed by the action of proteolytic enzymes. Its molecular structure has not yet been elucidated. It is not found accumulated in the cells but synthesized and released by some white cells mainly by sensitized mast cells and polymorphonuclear leukocytes after challenging with the specific antigen. The SRS-A is a powerful pharmacodynamic agent, it produces contraction of the bronchial smooth muscle in doses of nanograms. It probably plays a predominant role in the physiopathology of asthma. The chain of chemical reactions elicited by antigen-antibody interaction does not end with the release of SRS-A and the other mediators (histamine, eosinophil chemotactic factor of anaphylaxis, ECF-A), on the contrary, these mediators especially SRS-A induce the release of prostaglandins of type E (PGE1 and PGE2) which produce bronchodilatation and inhibit the release of SRS-A itself, perhaps being a selfregulating mechanism. The PGF2a, on the other hand, produces bronchoconstriction. The release of SRS-A is also inhibited by the action of diethyl-carbamazine and especially by sodium chromoglicate and compound AH-7725. From the biochemical point of view it is found that the antigen Igells, a serine esterase, initiating several chemical reactions whose consequence is a decrease in the cAMP concentration. This reduction in the cAMP intracellular level is followed by synthesis and excretion of the SRS-A as well as by the aggregation of the microtubules and excretion of the stored histamine. The PGE (1 and 2) acting on one type of membrane receptor and the beta-agonist catecholamines on another produce a common phenomenon: the activation of the adenylcyclase whcih produces the increase of the concentration of cAMP and inhibits the release of mediators of the anapylactic reaction. The parasympathetic system through its chemical mediator acethylcholine, by a mechanism in whcih adenycyclase is not involved is also capable of stimulating the release of histamine and SRS-A. Something similar happens with PGF2a. In conclusion, self-regulatory mechansims for the release of mediators of the anaphylactic reactions may exist. The \"perpetuation\" of an asthamtic reaction would signify a failure of these self-regulatory mechanisms due to, for example, to a temporary block of the beta-adrenergic receptors, overstimulation of the alfa-receptors or insufficient production of PGE or a transformation of the PGE in PGF."}
{"id": "PMID:5883", "title": "Polyarteritis in children.", "content": "Polyarteritis was diagnosed in three girls, 9 to 10 years old, by kidney and skin biopsies. They were treated with a combination of prednisone (1.5 to 2 mg/kg) and cyclophosphamide (2 mg/kg) for up to 12 months. The illness was severe in all three, complicated by hypertension, seizures, pulmonary infiltrates, renal failure, or hallucinations. All three patients are alive and well with no or minimal residual symptoms two to three years after therapy was discontinued. The treatment with corticosteroids or with a combination of steroids and immunosuppressive drugs seems to improve the prognosis of polyarteritis considerably.", "contents": "Polyarteritis in children. Polyarteritis was diagnosed in three girls, 9 to 10 years old, by kidney and skin biopsies. They were treated with a combination of prednisone (1.5 to 2 mg/kg) and cyclophosphamide (2 mg/kg) for up to 12 months. The illness was severe in all three, complicated by hypertension, seizures, pulmonary infiltrates, renal failure, or hallucinations. All three patients are alive and well with no or minimal residual symptoms two to three years after therapy was discontinued. The treatment with corticosteroids or with a combination of steroids and immunosuppressive drugs seems to improve the prognosis of polyarteritis considerably."}
{"id": "PMID:5885", "title": "Changes in mucosal and venous histamine concentrations during instillation of ethanol in the canine stomach.", "content": "Histamine concentrations in the gastric mucosa, gastric vein blood, and gastric contents were measured after instillation of 300 ml of 40%, 20% and 12.5%, vol/vol, ethanol intragastrically for 30 min in anesthetized dogs. The mean histamine concentration in the gastric mucosa, gastric vein blood, and gastric contents in dogs treated with 40% ethanol was significantly higher than in dogs treated with sodium chloride (NaCl). Serial studies of the gastric vein blood of the ethanol-treated dogs should significant elevation of histamine concentrations for 2 hr after instillation of 40% ethanol, but less increases at 20 and 30 min after instillation of 12.5% and 20%, respectively. No change was observed after administration of 50% glucose and 25% mannitol. Morphologically, the gastric mucosa of the ethanol-treated dogs was edematous, congested and hemorrhagic. The severity of these changes increased with the concentration used. The mucosa of the dogs treated with sodium chloride, glucose, or mannitol was normal. The factors that may underlie the increase in histamine concentrations in the gastric vein blood and the possible relation of such an increase to the morphologic alterations are discussed.", "contents": "Changes in mucosal and venous histamine concentrations during instillation of ethanol in the canine stomach. Histamine concentrations in the gastric mucosa, gastric vein blood, and gastric contents were measured after instillation of 300 ml of 40%, 20% and 12.5%, vol/vol, ethanol intragastrically for 30 min in anesthetized dogs. The mean histamine concentration in the gastric mucosa, gastric vein blood, and gastric contents in dogs treated with 40% ethanol was significantly higher than in dogs treated with sodium chloride (NaCl). Serial studies of the gastric vein blood of the ethanol-treated dogs should significant elevation of histamine concentrations for 2 hr after instillation of 40% ethanol, but less increases at 20 and 30 min after instillation of 12.5% and 20%, respectively. No change was observed after administration of 50% glucose and 25% mannitol. Morphologically, the gastric mucosa of the ethanol-treated dogs was edematous, congested and hemorrhagic. The severity of these changes increased with the concentration used. The mucosa of the dogs treated with sodium chloride, glucose, or mannitol was normal. The factors that may underlie the increase in histamine concentrations in the gastric vein blood and the possible relation of such an increase to the morphologic alterations are discussed."}
{"id": "PMID:5886", "title": "Organic anions induce colinic secretion.", "content": "Experiments were conducted by instilling test solutions into the cleaned colon of anesthetized rats. Isotonic test solutions at an acid (2.9% or neutral (7.0) pH and containing acetic acid or acetate ions were used. At the lower pH, acetic acid was absorbed well absorbed and the colon absorbed fluid. The secretory effect could not be reproduced by hydrochloric acid solutions at pH 2.9. Fluid secretion induced by acetic acid was associated with discharge of mucus from goblet cells. The interference of colonic absorption by acetic acid might be important in some diarrheal diseases.", "contents": "Organic anions induce colinic secretion. Experiments were conducted by instilling test solutions into the cleaned colon of anesthetized rats. Isotonic test solutions at an acid (2.9% or neutral (7.0) pH and containing acetic acid or acetate ions were used. At the lower pH, acetic acid was absorbed well absorbed and the colon absorbed fluid. The secretory effect could not be reproduced by hydrochloric acid solutions at pH 2.9. Fluid secretion induced by acetic acid was associated with discharge of mucus from goblet cells. The interference of colonic absorption by acetic acid might be important in some diarrheal diseases."}
{"id": "PMID:5888", "title": "Residues in antibiotic preparations, i: scanning electron microscopic studies of surface topography.", "content": "The surface characteristics of residues obtained from several commercial antibiotic products were studied using scanning electron microscopy. The photomicrographs showed the presence of particulates possessing crystalline or amorphous properties with particle sizes ranging from 1 mum to several mum. Small, well-defined, granular crystalline particulates seemed to predominate in residues of products which were processed  under optimum pH conditions. Coalescing or aggregating of small crystalline particles (1-10mum) to form larger masses was interpreted as a sign of instability of the antibiotic. Most of the penicillin and semisynthetic penicillins produced residues that were characterized as amorphous, flaky, bulky and of no distinct shape. Such structures were attributed to the drying of gelatinous particulates. The possible sources and causes of the occurrence of these particulates are discussed. It appears that in many of the products the particulates are product-related rather than process-related, and subtle degradation may be involved. Advice is given to practitioners regarding the preparation, storage and administration of these products.", "contents": "Residues in antibiotic preparations, i: scanning electron microscopic studies of surface topography. The surface characteristics of residues obtained from several commercial antibiotic products were studied using scanning electron microscopy. The photomicrographs showed the presence of particulates possessing crystalline or amorphous properties with particle sizes ranging from 1 mum to several mum. Small, well-defined, granular crystalline particulates seemed to predominate in residues of products which were processed  under optimum pH conditions. Coalescing or aggregating of small crystalline particles (1-10mum) to form larger masses was interpreted as a sign of instability of the antibiotic. Most of the penicillin and semisynthetic penicillins produced residues that were characterized as amorphous, flaky, bulky and of no distinct shape. Such structures were attributed to the drying of gelatinous particulates. The possible sources and causes of the occurrence of these particulates are discussed. It appears that in many of the products the particulates are product-related rather than process-related, and subtle degradation may be involved. Advice is given to practitioners regarding the preparation, storage and administration of these products."}
{"id": "PMID:5889", "title": "Residues in antibiotic preparations, ii: effect of pH on the nature and level of particulate matter in sodium cephalothin intravenous solutions.", "content": "The effect of pH on the extent and nature of particulate contamination in sodium cephalothin intravenous solutions was studied. The extent of particulate contamination was determined by microscopic and automatic electronic counting procedures, and the physical nature of the particles was determined using scanning electron microscopy. At low pH values (i.e., 4.9--5.9), an amorphous residue was predominant, while at higher pH values (6.9--7.8), the gelatinous nature of the residue disappeared and small crystalline particulates of varying sizes were predominant. The level of particulate contamination (particles over 10 mum in size) decreased with an increase in pH to a minimum level between pH 7 and 8. Advice is given to practitioners regarding the preparation of sodium cephalothin solutions.", "contents": "Residues in antibiotic preparations, ii: effect of pH on the nature and level of particulate matter in sodium cephalothin intravenous solutions. The effect of pH on the extent and nature of particulate contamination in sodium cephalothin intravenous solutions was studied. The extent of particulate contamination was determined by microscopic and automatic electronic counting procedures, and the physical nature of the particles was determined using scanning electron microscopy. At low pH values (i.e., 4.9--5.9), an amorphous residue was predominant, while at higher pH values (6.9--7.8), the gelatinous nature of the residue disappeared and small crystalline particulates of varying sizes were predominant. The level of particulate contamination (particles over 10 mum in size) decreased with an increase in pH to a minimum level between pH 7 and 8. Advice is given to practitioners regarding the preparation of sodium cephalothin solutions."}
{"id": "PMID:5890", "title": "Compatibility of penicillin and ascorbic acid injection.", "content": "The stability of Potassium Penicillin G, USP, when mixed with Ascorbic Acid Injection, USP, in 5% Dextrose Injection, USP, was studied. The change in concentration over an eight-hour period of potassium penicillin G in the admixture was determined by the hydroxylamine colorimetric assay method and the microbiological assay method. The stability of penicillin was not adversely affected by the presence of sodium ascorbate. Reports of incompatibilities between penicillin and ascorbic acid are a function of pH rather than a characteristic of the ascorbate ion. Articles reporting studies involving ascorbic acid should specify whether the work refers to the use of ascorbic acid or Ascorbic Acid Injection, USP. Confusion in the literature could be reduced by changing the official title from Ascorbic Acid Injection to Sodium Ascorbate Injection.", "contents": "Compatibility of penicillin and ascorbic acid injection. The stability of Potassium Penicillin G, USP, when mixed with Ascorbic Acid Injection, USP, in 5% Dextrose Injection, USP, was studied. The change in concentration over an eight-hour period of potassium penicillin G in the admixture was determined by the hydroxylamine colorimetric assay method and the microbiological assay method. The stability of penicillin was not adversely affected by the presence of sodium ascorbate. Reports of incompatibilities between penicillin and ascorbic acid are a function of pH rather than a characteristic of the ascorbate ion. Articles reporting studies involving ascorbic acid should specify whether the work refers to the use of ascorbic acid or Ascorbic Acid Injection, USP. Confusion in the literature could be reduced by changing the official title from Ascorbic Acid Injection to Sodium Ascorbate Injection."}
{"id": "PMID:5892", "title": "Self-injurious behavior in schizophrenic and retarded children.", "content": "Self-injurious behavior  is a problem with some children who are primarily nonverval and low-functioning. This behavior has resulted in management difficulties far out of proportion to its incidence. In the present paper, we have considered possible operant and respondent paradigms instrumental in the acquisition and maintenance of several different topographies of self-injurious behavior. Support for these paradigms was gathered from existing epidemiological literature dealing with humans and primates and from the literature concerned with treatment of self-injurious behavior. Immediate outcome and results of subsequent follow-up were presented as a function of type of intervention, the nature of positive reinforcement utilized, and the topography of the self-injurious response involved. Implications were drawn for future research and treatment.", "contents": "Self-injurious behavior in schizophrenic and retarded children. Self-injurious behavior  is a problem with some children who are primarily nonverval and low-functioning. This behavior has resulted in management difficulties far out of proportion to its incidence. In the present paper, we have considered possible operant and respondent paradigms instrumental in the acquisition and maintenance of several different topographies of self-injurious behavior. Support for these paradigms was gathered from existing epidemiological literature dealing with humans and primates and from the literature concerned with treatment of self-injurious behavior. Immediate outcome and results of subsequent follow-up were presented as a function of type of intervention, the nature of positive reinforcement utilized, and the topography of the self-injurious response involved. Implications were drawn for future research and treatment."}
{"id": "PMID:5893", "title": "Fetal acid-base balance. I. Interdependence of maternal and fetal PCO2 and bicarbonate concentration.", "content": "This paper presents the results of measurements of the acid-base and gaseous status of maternal and fetal capillary blood at the time of amniotomy, before the onset of labor. The correlation coefficient between maternal and fetal bicarbonate concentration is 0.6, and that between maternal and fetal PCO2 is 0.31. From the results obtained, as well as from a survey of other work in the field, it is proposed that the diffusion of carbon dioxide across the placenta could not explain some of the findings and that bicarbonate concentrations equilibrate across the placenta.", "contents": "Fetal acid-base balance. I. Interdependence of maternal and fetal PCO2 and bicarbonate concentration. This paper presents the results of measurements of the acid-base and gaseous status of maternal and fetal capillary blood at the time of amniotomy, before the onset of labor. The correlation coefficient between maternal and fetal bicarbonate concentration is 0.6, and that between maternal and fetal PCO2 is 0.31. From the results obtained, as well as from a survey of other work in the field, it is proposed that the diffusion of carbon dioxide across the placenta could not explain some of the findings and that bicarbonate concentrations equilibrate across the placenta."}
{"id": "PMID:5894", "title": "Breathing patterns before death in fetal lambs.", "content": "Continuous observations in 16 fetal lambs over many days before death in utero from hypoxia, asphyxia, infection, and other causes have shown that death is preceded by variable changes in breathing movements. There was always a prolonged period of apnea succeeded by continuous abnormal breathing in six lambs and by gasping or brief episodes of abnormal breathing in the remainder. These abnormal patterns are described as a warning of what may be encountered in the human fetus.", "contents": "Breathing patterns before death in fetal lambs. Continuous observations in 16 fetal lambs over many days before death in utero from hypoxia, asphyxia, infection, and other causes have shown that death is preceded by variable changes in breathing movements. There was always a prolonged period of apnea succeeded by continuous abnormal breathing in six lambs and by gasping or brief episodes of abnormal breathing in the remainder. These abnormal patterns are described as a warning of what may be encountered in the human fetus."}
{"id": "PMID:5895", "title": "The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy.", "content": "Intrapartum electronic fetal heart rate monitoring of the high-risk obstetric patient is thought to improve the perinatal outcome. A prospective randomized study of 483 high-risk obstetric patients in labor was carried out comparing the effectiveness of electronic fetal monitoring with auscultation of fetal heart tones. The infant outcome was measured by neonatal death, Apgar scores, cord blood gases, and neonatal nursery morbidity. There were no differences in the infant outcomes in any measured category between the electronically monitored group and the auscultated group. The cesarean section rate was markedly increased in the monitored group (16.5 vs. 6.8 per cent in the auscultated patients). The presumptive benefits of electronic fetal monitoring for improving fetal outcome were not found in this study.", "contents": "The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy. Intrapartum electronic fetal heart rate monitoring of the high-risk obstetric patient is thought to improve the perinatal outcome. A prospective randomized study of 483 high-risk obstetric patients in labor was carried out comparing the effectiveness of electronic fetal monitoring with auscultation of fetal heart tones. The infant outcome was measured by neonatal death, Apgar scores, cord blood gases, and neonatal nursery morbidity. There were no differences in the infant outcomes in any measured category between the electronically monitored group and the auscultated group. The cesarean section rate was markedly increased in the monitored group (16.5 vs. 6.8 per cent in the auscultated patients). The presumptive benefits of electronic fetal monitoring for improving fetal outcome were not found in this study."}
{"id": "PMID:5896", "title": "Evaluation of redox state of isolated perfused rat lung.", "content": "The metabolic responsiveness of lung tissue to inhibition of oxidative metabolism was determined by measurement of the redox state of the isolated perfused and ventilated rat lung. Changes in redox state were evaluated by fluorescence from the lung surface at wavelengths suitable for reduced pyridine nucleotides and by measurement of the ratios of redox couples in rapidly frozen lung tissue. Maximal change of redox state was observed during ventilation with carbon monoxide; surface fluorescence increased 6.6%, lactate/pyruvate increased 5.8 times, glycerol 3-P/dihydroxyacetone-P increased fourfold and glutamate/alpha-ketoglutarate doubled. KCN infusion resulted in similar changes. Hypoxia produced with N2 ventilation resulted in less than maximal changes in redox couple ratios until alveolar PO2 was reduced below 0.1 mmHg. Redox changes observed during infusion of 0.5 mM aminoxyacetic acid suggested that maintenance of cytoplasmic redox state depended on functioning of a malate-aspartate \"shuttle.\" The isolated perfused lung appears suitable to study factors controlling pulmonary parenchymal oxidative metabolism. The results emphasize the need for ventilation with CO to establish intracellular anoxia.", "contents": "Evaluation of redox state of isolated perfused rat lung. The metabolic responsiveness of lung tissue to inhibition of oxidative metabolism was determined by measurement of the redox state of the isolated perfused and ventilated rat lung. Changes in redox state were evaluated by fluorescence from the lung surface at wavelengths suitable for reduced pyridine nucleotides and by measurement of the ratios of redox couples in rapidly frozen lung tissue. Maximal change of redox state was observed during ventilation with carbon monoxide; surface fluorescence increased 6.6%, lactate/pyruvate increased 5.8 times, glycerol 3-P/dihydroxyacetone-P increased fourfold and glutamate/alpha-ketoglutarate doubled. KCN infusion resulted in similar changes. Hypoxia produced with N2 ventilation resulted in less than maximal changes in redox couple ratios until alveolar PO2 was reduced below 0.1 mmHg. Redox changes observed during infusion of 0.5 mM aminoxyacetic acid suggested that maintenance of cytoplasmic redox state depended on functioning of a malate-aspartate \"shuttle.\" The isolated perfused lung appears suitable to study factors controlling pulmonary parenchymal oxidative metabolism. The results emphasize the need for ventilation with CO to establish intracellular anoxia."}
{"id": "PMID:5897", "title": "Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis.", "content": "Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.", "contents": "Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis. Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats."}
{"id": "PMID:5898", "title": "Histidine decarboxylase-mediated histamine synthesis in glomeruli from rat kidneys.", "content": "Enzymatic histamine synthesis by renal glomeruli of the rat has been examined. Assays of the partially purified enzyme demonstrated a pH optimum of 6.2, a Michaelis-Menten constant of 2.4 X 10(-4) histidine, and lack of potentiation by benzene. These data thus indicate that renal glomeruli contain the histidine-specific histidine decarboxylase.", "contents": "Histidine decarboxylase-mediated histamine synthesis in glomeruli from rat kidneys. Enzymatic histamine synthesis by renal glomeruli of the rat has been examined. Assays of the partially purified enzyme demonstrated a pH optimum of 6.2, a Michaelis-Menten constant of 2.4 X 10(-4) histidine, and lack of potentiation by benzene. These data thus indicate that renal glomeruli contain the histidine-specific histidine decarboxylase."}
{"id": "PMID:5899", "title": "Effects of temperature transients on gas exchange and acid-base status of turtles.", "content": "Pulmonary ventilation (VE), O2 consumption (VO2), and CO2 production (VCO2) were measured continuously on each of 10 turtles, Pseudemys scripta elegans, at 20 degrees C, during and for 1 h after heating to 30 degrees C and during and for 1 h after cooling to 20 degrees C. In seven of the animals, arterial blood was sampled at the three temperature plateaus. Ventilatory ratios (VE/VO2 and VE/VCO2) and metabolic rate adjusted promptly to temperature change, stabilizing at values similar to those observed previously in turtles following 1 day or more at each temperature. Likewise, mean blood pH and PCO2 values conformed both in absolute values and in temperature-dependence to data previously obtained from animals exposed to the various temperatures for longer time periods or from turtle blood thermally equilibrated in vitro. Total plasma [CO2] did not change significantly, suggesting that steady-state CO2 exchange prevailed throughout the experiment. In accordance with this, R(VCO2/VO2) did not change significantly during the 20-30 degrees C transition; however, R rose during the 30-20 degrees C transition, suggesting possible hyperventilation at this stage. We conclude that the respiratory control of blood acid-base status adjusts rapidly to temperature change in the turtle and its adjustment minimizes disturbance to CO2 balance.", "contents": "Effects of temperature transients on gas exchange and acid-base status of turtles. Pulmonary ventilation (VE), O2 consumption (VO2), and CO2 production (VCO2) were measured continuously on each of 10 turtles, Pseudemys scripta elegans, at 20 degrees C, during and for 1 h after heating to 30 degrees C and during and for 1 h after cooling to 20 degrees C. In seven of the animals, arterial blood was sampled at the three temperature plateaus. Ventilatory ratios (VE/VO2 and VE/VCO2) and metabolic rate adjusted promptly to temperature change, stabilizing at values similar to those observed previously in turtles following 1 day or more at each temperature. Likewise, mean blood pH and PCO2 values conformed both in absolute values and in temperature-dependence to data previously obtained from animals exposed to the various temperatures for longer time periods or from turtle blood thermally equilibrated in vitro. Total plasma [CO2] did not change significantly, suggesting that steady-state CO2 exchange prevailed throughout the experiment. In accordance with this, R(VCO2/VO2) did not change significantly during the 20-30 degrees C transition; however, R rose during the 30-20 degrees C transition, suggesting possible hyperventilation at this stage. We conclude that the respiratory control of blood acid-base status adjusts rapidly to temperature change in the turtle and its adjustment minimizes disturbance to CO2 balance."}
{"id": "PMID:5900", "title": "Direct effects of various catecholamines on liver circulation in dogs.", "content": "As measured by electromagnetic blood flow transducers, direct infusion of epinephrine, norepinephrine, and dopamine into the portal vein (PV) produced a 40-50% decrease in hepatic arterial (HA) blood flow; isoproterenol increased HA flow by about 69%. No changes in PV flow or pressure were observed. Direct HA infusion of the vasoconstrictors decreased HA flow by amounts comparable to those occurring after PV infusion. However, HA infusion of isoproterenol increased HA flow only 15% suggesting a difference in beta-receptor population in the two vessels. When infused directly into the superior mesenteric artery (SMA), epinephrine and norepinephrine reduced SMA flow by about 45% and PV flow by 20-25%; HA flow increased 6-8%. Infusion of isoproterenol and dopamine into SMA increased SMA flow by 115% and 206% and PV flow by 60% and 70%, respectively, whereas HA flow decreased by 25% and 50%. Portal vein pressure increased less than 3 mmHg. Alpha- and beta-receptor blockade of the liver did not change significantly the alterations in hepatic arterial blood flow that were secondary to changes in portal venous blood flow. It is likely that regulation of hepatic arterial flow resides in mechanisms located within the liver sinusoids.", "contents": "Direct effects of various catecholamines on liver circulation in dogs. As measured by electromagnetic blood flow transducers, direct infusion of epinephrine, norepinephrine, and dopamine into the portal vein (PV) produced a 40-50% decrease in hepatic arterial (HA) blood flow; isoproterenol increased HA flow by about 69%. No changes in PV flow or pressure were observed. Direct HA infusion of the vasoconstrictors decreased HA flow by amounts comparable to those occurring after PV infusion. However, HA infusion of isoproterenol increased HA flow only 15% suggesting a difference in beta-receptor population in the two vessels. When infused directly into the superior mesenteric artery (SMA), epinephrine and norepinephrine reduced SMA flow by about 45% and PV flow by 20-25%; HA flow increased 6-8%. Infusion of isoproterenol and dopamine into SMA increased SMA flow by 115% and 206% and PV flow by 60% and 70%, respectively, whereas HA flow decreased by 25% and 50%. Portal vein pressure increased less than 3 mmHg. Alpha- and beta-receptor blockade of the liver did not change significantly the alterations in hepatic arterial blood flow that were secondary to changes in portal venous blood flow. It is likely that regulation of hepatic arterial flow resides in mechanisms located within the liver sinusoids."}
{"id": "PMID:5901", "title": "Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels.", "content": "Plasma chlorpromazine (CPZ) levels of 50 psychotic inpatients were measured by gas liquid chromatography; the clinical progress of 29 of these patients with acute psychoses was also assessed. CPZ levels of 50-300 ng/ml were usually associated with clinical improvement; there was also a relationship between CPZ levels and increases in certain symptoms. The 50-300 ng/ml level was best attained by doses of 400-800 mg/day. Trihexyphenidyl decreased plasma CPZ by a mean of 44.7% in 12 of 15 patients. A single 400-800-mg dose of CPZ at bedtime produced steady states equal to or better than those achieved with multiple doses. Those patients who failed to attain CPZ levels of more than 70 ng/ml despite doses of 400-1000 mg/day were receiving lithium throughout the study and had discharge diagnoses of manic-depressive psychosis, manic type, and schizo-affective schizophrenia--a finding with implications for future research.", "contents": "Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels. Plasma chlorpromazine (CPZ) levels of 50 psychotic inpatients were measured by gas liquid chromatography; the clinical progress of 29 of these patients with acute psychoses was also assessed. CPZ levels of 50-300 ng/ml were usually associated with clinical improvement; there was also a relationship between CPZ levels and increases in certain symptoms. The 50-300 ng/ml level was best attained by doses of 400-800 mg/day. Trihexyphenidyl decreased plasma CPZ by a mean of 44.7% in 12 of 15 patients. A single 400-800-mg dose of CPZ at bedtime produced steady states equal to or better than those achieved with multiple doses. Those patients who failed to attain CPZ levels of more than 70 ng/ml despite doses of 400-1000 mg/day were receiving lithium throughout the study and had discharge diagnoses of manic-depressive psychosis, manic type, and schizo-affective schizophrenia--a finding with implications for future research."}
{"id": "PMID:5902", "title": "Accidental hypothermia: core rewarming with partial bypass.", "content": "Three patients with profound hypothermia were treated by rewarming on partial bypass. Two surivived and have normal mental and metabolic functions. The resuscitation of the hypothermic patient should be approached with enthusiasm since the outcome is often much better than expected from initial vital signs and neurologic examination. To avoid ventricular fibrillation the patient should be handled gently and an effort should be made to keep the patient well oxygenated and the pH normal. Blood gases should be measured often and corrected for temperature. The potassium concentration and hydration status of the patient should also be monitored closely. The rewarming of profoundly hypothermic patients can readily be accomplished with a pump oxygenator and heat exchanger. The indications for this method are not established from our small experience and the few cases reported in the literature. Certainly ventricular fibrillation is a compelling indication. Patients with frozen extremities might also benefit from this method since theoretically tissue salvage would be increased. Finally, those patients who do not respond rapidly to external rewarming may be at less risk of ventricular fibrillation if rewarmed on bypass.", "contents": "Accidental hypothermia: core rewarming with partial bypass. Three patients with profound hypothermia were treated by rewarming on partial bypass. Two surivived and have normal mental and metabolic functions. The resuscitation of the hypothermic patient should be approached with enthusiasm since the outcome is often much better than expected from initial vital signs and neurologic examination. To avoid ventricular fibrillation the patient should be handled gently and an effort should be made to keep the patient well oxygenated and the pH normal. Blood gases should be measured often and corrected for temperature. The potassium concentration and hydration status of the patient should also be monitored closely. The rewarming of profoundly hypothermic patients can readily be accomplished with a pump oxygenator and heat exchanger. The indications for this method are not established from our small experience and the few cases reported in the literature. Certainly ventricular fibrillation is a compelling indication. Patients with frozen extremities might also benefit from this method since theoretically tissue salvage would be increased. Finally, those patients who do not respond rapidly to external rewarming may be at less risk of ventricular fibrillation if rewarmed on bypass."}
{"id": "PMID:5924", "title": "Premedicant drugs and gastric juice pH and volume in pediatric patients.", "content": "The effects of premedication on gastric juice volume and pH were evaluated in five groups of 206 pediatric patients undergoing elective surgical procedures: Group 1 (Control) received no premedication; Group 2 was given morphine sulfate and pentobarbital as premedicants. The other groups received, in addition to morphine and pentobarbital, atropine (Group 3), scopolamine (Group 4), or glycopyrrolate (Group 5). After endotracheal intubation, gastric aspirates were examined for volume, pH and color. Neither premedication with morphine and pentobarbital nor addition of atropine or scopolamine to the premedication significantly altered volume. In patients treated with glycopyrrolate, volume was reduced to less than a third of that of patients in Group 1 (P less than 0.001), and the percentage of pH's higher than 2.5 was significantly greater than in other groups. The incidences of unobtainable samples and samples with pH's higher than 2.5 were greatest with atropine (32.0 per cent, P less than 0.05) and glycopyrrolate (58.1 per cent, P less than 0.01). In 60 per cent of the bile-stained specimens, pH's were below 2.5. It is concluded that because of its selective inhibitory effect on gastric acid secretions, glycopyrrolate appears superior to other anticholinergic drugs. The reduction of gastric juice volume and acidity produced by glycopyrrolate would have important clinical implications in case of accidental aspiration. It is also concluded that bile staining of gastric contents is not a reliable indicator of gastric juice pH.", "contents": "Premedicant drugs and gastric juice pH and volume in pediatric patients. The effects of premedication on gastric juice volume and pH were evaluated in five groups of 206 pediatric patients undergoing elective surgical procedures: Group 1 (Control) received no premedication; Group 2 was given morphine sulfate and pentobarbital as premedicants. The other groups received, in addition to morphine and pentobarbital, atropine (Group 3), scopolamine (Group 4), or glycopyrrolate (Group 5). After endotracheal intubation, gastric aspirates were examined for volume, pH and color. Neither premedication with morphine and pentobarbital nor addition of atropine or scopolamine to the premedication significantly altered volume. In patients treated with glycopyrrolate, volume was reduced to less than a third of that of patients in Group 1 (P less than 0.001), and the percentage of pH's higher than 2.5 was significantly greater than in other groups. The incidences of unobtainable samples and samples with pH's higher than 2.5 were greatest with atropine (32.0 per cent, P less than 0.05) and glycopyrrolate (58.1 per cent, P less than 0.01). In 60 per cent of the bile-stained specimens, pH's were below 2.5. It is concluded that because of its selective inhibitory effect on gastric acid secretions, glycopyrrolate appears superior to other anticholinergic drugs. The reduction of gastric juice volume and acidity produced by glycopyrrolate would have important clinical implications in case of accidental aspiration. It is also concluded that bile staining of gastric contents is not a reliable indicator of gastric juice pH."}
{"id": "PMID:5920", "title": "Arterial hypoxemia caused by intravenous ketamine.", "content": "Ketamine given IV in a dose of 2 mg/kg caused a significant reduction in Pao2 in 7 patients spontaneously breathing with an unassisted airway. Under the same conditions, in 7 patients, ketamine (2 mg/kg IV) preceded by diazepam (0.2 mg/kg IV) also caused a reduction in Pao2 not significantly different from that caused by ketamine. In some patients, alarmingly low levels of Pao2 ( less than or equal to 40 torr) were seen following ketamine administration. Based on these findings, the authors recommend that O2 and ventilatory assistance accompany ketamine given IV for anesthesia.", "contents": "Arterial hypoxemia caused by intravenous ketamine. Ketamine given IV in a dose of 2 mg/kg caused a significant reduction in Pao2 in 7 patients spontaneously breathing with an unassisted airway. Under the same conditions, in 7 patients, ketamine (2 mg/kg IV) preceded by diazepam (0.2 mg/kg IV) also caused a reduction in Pao2 not significantly different from that caused by ketamine. In some patients, alarmingly low levels of Pao2 ( less than or equal to 40 torr) were seen following ketamine administration. Based on these findings, the authors recommend that O2 and ventilatory assistance accompany ketamine given IV for anesthesia."}
{"id": "PMID:5921", "title": "Clinical investigation of a new intravenous anesthetic--etoxadrol hydrochloride (CL-1848; U-37862A).", "content": "Twenty-eight patients were anesthetized with etoxadrol as primary agent. The anesthesia produced was characterized by profound analgesia and amnesia, while pharyngeal and laryngeal reflexes, as well as swallowing and lid reflexes, remained active. Systolic, diastolic, and pulse pressure were slightly increased, with associated tachycardia and tachypnea. A dose of 0.75 mg/kg produced anesthesia for an average of 26 (14 to 53) minutes. Alternating nystagmus was present for several hours and associated with dreams and/or visions that were pleasing to most patients. Six patients, however, had unpleasant dreams for up to 24 hours. One patient given an excessive dose (4.65 mg/kg) was cataleptic, amnesic, and analgesic for 6 days. The occurrence of unpleasant dreams and aberrations in over 20% of the patients suggests that the drug probably has little usefulness in anesthesia. However, the extreme safety of the drug (an LD50 equal to some 20 to 40 times the ED50) and the prolonged analgesia justified clinical testing. There was no evidence of metabolic or systemic organ system change from any of the clinical laboratory studies.", "contents": "Clinical investigation of a new intravenous anesthetic--etoxadrol hydrochloride (CL-1848; U-37862A). Twenty-eight patients were anesthetized with etoxadrol as primary agent. The anesthesia produced was characterized by profound analgesia and amnesia, while pharyngeal and laryngeal reflexes, as well as swallowing and lid reflexes, remained active. Systolic, diastolic, and pulse pressure were slightly increased, with associated tachycardia and tachypnea. A dose of 0.75 mg/kg produced anesthesia for an average of 26 (14 to 53) minutes. Alternating nystagmus was present for several hours and associated with dreams and/or visions that were pleasing to most patients. Six patients, however, had unpleasant dreams for up to 24 hours. One patient given an excessive dose (4.65 mg/kg) was cataleptic, amnesic, and analgesic for 6 days. The occurrence of unpleasant dreams and aberrations in over 20% of the patients suggests that the drug probably has little usefulness in anesthesia. However, the extreme safety of the drug (an LD50 equal to some 20 to 40 times the ED50) and the prolonged analgesia justified clinical testing. There was no evidence of metabolic or systemic organ system change from any of the clinical laboratory studies."}
{"id": "PMID:5922", "title": "The effect of enflurane, isoflurane, fluroxene, methoxyflurane and diethyl ether anesthesia on ouabain tolerance in the dog.", "content": "Digitalis tolerance in dogs anesthetized with enflurane, isoflurane, fluroxene, methoxyflurane, and diethyl ether was compared with that in dogs anesthetized with pentobarbital. Ouabain dosage needed to cause ventricular tachycardia was significantly higher than that of pentobarbital with all agents except fluroxene, as was the LD50. The relative potency of these anesthetics in converting ouabain-induced ventricular tachycardia to sinus rhythm, in order of descending effectiveness, was: diethyl ether, methoxyflurane, enflurane, fluroxene, isoflurane, pentobarbital.", "contents": "The effect of enflurane, isoflurane, fluroxene, methoxyflurane and diethyl ether anesthesia on ouabain tolerance in the dog. Digitalis tolerance in dogs anesthetized with enflurane, isoflurane, fluroxene, methoxyflurane, and diethyl ether was compared with that in dogs anesthetized with pentobarbital. Ouabain dosage needed to cause ventricular tachycardia was significantly higher than that of pentobarbital with all agents except fluroxene, as was the LD50. The relative potency of these anesthetics in converting ouabain-induced ventricular tachycardia to sinus rhythm, in order of descending effectiveness, was: diethyl ether, methoxyflurane, enflurane, fluroxene, isoflurane, pentobarbital."}
{"id": "PMID:5923", "title": "An evaluation of memory under regional anesthesia with IV lorazepam as a premedicant.", "content": "Forty male volunteer patients undergoing regional anesthesia were evaluated for alertness and memory in a double-blind study which compared IV lorazepam (4 mg) plus IM meperidine (50 mg) with IV placebo plus IM meperidine (50 mg) as premedicants. The data indicate no significant retrograde effects. Significant differences at all measurement points from 20 minutes to 3 hours following IV drug administration indicated greater sedation and less recall and recognition of events and stimuli (auditory and visual) with the combination of lorazepam and meperidine than with placebo and meperidine. A significant number of patients over age 40 were judged to be excessively sedated after administration of lorazepam. However, respiration, blood pressure, and pulse did not appear to be differentially affected by lorazepam and there were no adverse changes even in patients considered to be oversedated.", "contents": "An evaluation of memory under regional anesthesia with IV lorazepam as a premedicant. Forty male volunteer patients undergoing regional anesthesia were evaluated for alertness and memory in a double-blind study which compared IV lorazepam (4 mg) plus IM meperidine (50 mg) with IV placebo plus IM meperidine (50 mg) as premedicants. The data indicate no significant retrograde effects. Significant differences at all measurement points from 20 minutes to 3 hours following IV drug administration indicated greater sedation and less recall and recognition of events and stimuli (auditory and visual) with the combination of lorazepam and meperidine than with placebo and meperidine. A significant number of patients over age 40 were judged to be excessively sedated after administration of lorazepam. However, respiration, blood pressure, and pulse did not appear to be differentially affected by lorazepam and there were no adverse changes even in patients considered to be oversedated."}
{"id": "PMID:5926", "title": "[2 cases of chylothorax caused by catheterization of left large venous trunks].", "content": "The authors present two cases of almost certain catheterization of the thoracic duct, by infusion catheters placed in the large veins at the base of the neck (once in the left internal jugular, once in the left subclavian). Their clinical manifestaztions are the existence of a rapidly progressive pleural effusion, apart from the abnormal course of the catheter. Removal of the catheter is sufficient to lead to the disappearance of the symptomatology, so that it is difficult to speak of an accident as such, but rather of an incident. These incidents could be avoided by systematic radiography from the time that the catheter is placed in position or the positioning of the latter under control by brilliance amplifier.", "contents": "[2 cases of chylothorax caused by catheterization of left large venous trunks]. The authors present two cases of almost certain catheterization of the thoracic duct, by infusion catheters placed in the large veins at the base of the neck (once in the left internal jugular, once in the left subclavian). Their clinical manifestaztions are the existence of a rapidly progressive pleural effusion, apart from the abnormal course of the catheter. Removal of the catheter is sufficient to lead to the disappearance of the symptomatology, so that it is difficult to speak of an accident as such, but rather of an incident. These incidents could be avoided by systematic radiography from the time that the catheter is placed in position or the positioning of the latter under control by brilliance amplifier."}
{"id": "PMID:5927", "title": "[Complications of lignocaine].", "content": "In three cases, following cardiac surgery operations, the appearance of a sudden loss of consciousness followed by an epileptic - like crisis was recorded. The accidents have a relationship with an administration of lignocaine in the form of a perfusion. Description of the observations and discussion of the toxicity of the product.", "contents": "[Complications of lignocaine]. In three cases, following cardiac surgery operations, the appearance of a sudden loss of consciousness followed by an epileptic - like crisis was recorded. The accidents have a relationship with an administration of lignocaine in the form of a perfusion. Description of the observations and discussion of the toxicity of the product."}
{"id": "PMID:5928", "title": "[Use of a new long acting local anesthetic, etidocaine in anesthesia-resuscitation (Duranest)].", "content": "Our experiment covered 123 patients who were given this new preparation with long action for various types of local and regional anesthesia. In 9 cases of peridural administration for several days, the total doses were very high and tolerance excellent. Results were good for all local and regional anesthesia for which this product was used: - Good local and general tolerance - Short latency period - Duration constantly and regularly prolonged: an average of 3 hours for non-adrenalin forms and 5 hours for adrenalin forms.", "contents": "[Use of a new long acting local anesthetic, etidocaine in anesthesia-resuscitation (Duranest)]. Our experiment covered 123 patients who were given this new preparation with long action for various types of local and regional anesthesia. In 9 cases of peridural administration for several days, the total doses were very high and tolerance excellent. Results were good for all local and regional anesthesia for which this product was used: - Good local and general tolerance - Short latency period - Duration constantly and regularly prolonged: an average of 3 hours for non-adrenalin forms and 5 hours for adrenalin forms."}
{"id": "PMID:5929", "title": "[The MA 1 B respirator. Apropos of an experiment involving 91,300 hours of function].", "content": "Description of the working principle and the characteristics of the Bennet MA 1 B respirator, which is of the release of volume type with electro-mechanical functioning. Study of the advantages and drawbacks. During an experiment involving 91,300 hours of utilization of 21 sets of apparatus, 12 breakdowns concerning a mechanical or electrical component were recorded. No incident in the functioning of the electronic part of the system of control or of surveillance was noted. The reliability of the apparatus appears on the whole to be satisfactory, taking into account its remarkable working posibilities.", "contents": "[The MA 1 B respirator. Apropos of an experiment involving 91,300 hours of function]. Description of the working principle and the characteristics of the Bennet MA 1 B respirator, which is of the release of volume type with electro-mechanical functioning. Study of the advantages and drawbacks. During an experiment involving 91,300 hours of utilization of 21 sets of apparatus, 12 breakdowns concerning a mechanical or electrical component were recorded. No incident in the functioning of the electronic part of the system of control or of surveillance was noted. The reliability of the apparatus appears on the whole to be satisfactory, taking into account its remarkable working posibilities."}
{"id": "PMID:5934", "title": "[Enzyme system and coenzymes involved in the energy metabolism of leukocytes. Function and metabolism of polymorphonuclear neutrophils].", "content": "Mitochondria may be isolated from various types of leukocyte (neutrophil polymorphs and lymphocytes from human blood, neutrophil polymorphs and macrophages from peritoneal exudates of the guinea pig) after destruction by heparin of the cell membrane. This procedure is very simple and less traumatic for these subcellular structures than the usual mechanical procedures. The enzyme activities of the respiratory chain and oxygen consumption may be measured in these mitochondrial preparations. The oxygen consumption is determined using oxyhemoglobin which serves both as oxygen donor, as in the respiratory system in vivo, and as indicator of the reaction at 435.8 nm. The integrity of the mitochondria may be demonstrated by determination of the \"acceptor control index\", the existence of ADP phosphorylation coupled with oxygen consumption (phosphorylating oxidation) was proved in all the cells studied even if the ADP/O ratio can only be calculated for certain of them (lymphocytes, macrophages). In these cases, the ratios obtained are close to theoretical values whatever the oxidation substrate used. The mitochondria of leukemic cells have a higher oxidation activity than the corresponding reference cells. Determination of leukocyte coenzymes by enzyme cycling (NAD, NADH, NADP, NADPH) showed the following facts: -- Generally, the NAD concentrations remain constant, those of NADH increase whilst those of NADP and NADPH fall during incubation of neutrophil polymorphs in Dulbecco's medium. -- The metabolic changes observed during S. albi heat-induced endocytosis are in favour of simultaneous stimulation of NADH oxidase and NADPH oxidase in human polymorphs, and of NADPH oxidase in the corresponding cells of peritoneal exudates in guinea pigs.", "contents": "[Enzyme system and coenzymes involved in the energy metabolism of leukocytes. Function and metabolism of polymorphonuclear neutrophils]. Mitochondria may be isolated from various types of leukocyte (neutrophil polymorphs and lymphocytes from human blood, neutrophil polymorphs and macrophages from peritoneal exudates of the guinea pig) after destruction by heparin of the cell membrane. This procedure is very simple and less traumatic for these subcellular structures than the usual mechanical procedures. The enzyme activities of the respiratory chain and oxygen consumption may be measured in these mitochondrial preparations. The oxygen consumption is determined using oxyhemoglobin which serves both as oxygen donor, as in the respiratory system in vivo, and as indicator of the reaction at 435.8 nm. The integrity of the mitochondria may be demonstrated by determination of the \"acceptor control index\", the existence of ADP phosphorylation coupled with oxygen consumption (phosphorylating oxidation) was proved in all the cells studied even if the ADP/O ratio can only be calculated for certain of them (lymphocytes, macrophages). In these cases, the ratios obtained are close to theoretical values whatever the oxidation substrate used. The mitochondria of leukemic cells have a higher oxidation activity than the corresponding reference cells. Determination of leukocyte coenzymes by enzyme cycling (NAD, NADH, NADP, NADPH) showed the following facts: -- Generally, the NAD concentrations remain constant, those of NADH increase whilst those of NADP and NADPH fall during incubation of neutrophil polymorphs in Dulbecco's medium. -- The metabolic changes observed during S. albi heat-induced endocytosis are in favour of simultaneous stimulation of NADH oxidase and NADPH oxidase in human polymorphs, and of NADPH oxidase in the corresponding cells of peritoneal exudates in guinea pigs."}
{"id": "PMID:5930", "title": "[Use of the Cessna 206 for medical evacuations].", "content": "The CESSNA 206 aircraft belonging to the National Police Force has been used to effect medical evacuations. After describing the specifications of this aircraft and underlining its advantages (speed, autonomy, cost price) and its disadvantages (very small cabin, necessity of prepared landing grounds, sound level) compared with the helicopter generally used in similar circumstances, the authors conclude that this new aircraft could be used to advantage for evacuating medium-serious cases over distances greater than 200 kilometer provided that the cabin was modified. Even more than with the helicopter, the pilot must remain the judge concerning the technical flying possibilities of the aircraft, which is not pressurized and which has no defrosting equipment.", "contents": "[Use of the Cessna 206 for medical evacuations]. The CESSNA 206 aircraft belonging to the National Police Force has been used to effect medical evacuations. After describing the specifications of this aircraft and underlining its advantages (speed, autonomy, cost price) and its disadvantages (very small cabin, necessity of prepared landing grounds, sound level) compared with the helicopter generally used in similar circumstances, the authors conclude that this new aircraft could be used to advantage for evacuating medium-serious cases over distances greater than 200 kilometer provided that the cabin was modified. Even more than with the helicopter, the pilot must remain the judge concerning the technical flying possibilities of the aircraft, which is not pressurized and which has no defrosting equipment."}
{"id": "PMID:5931", "title": "[Incidence of deep venous thromboses in traumatology and methods of early detection].", "content": "In this work carried out at the Traumatology Centre in Strasbourg, out of 227 patients operated for a fracture situated between the pelvis and the tibial plateau, the authors endeavoured to show a thrombosis of the lower limbs. The means of exploration included in addition to the clinical and biological blood tests an isotopic, rheographic and phlebographic surveillance. The latter three ways of exploration are particularly viewed in this study, during which it was possible to demonstrate 44 p. 100 thrombo-embolic manifestations of which 38 p. 100 were detected only by the isotopic method, the phlebographic check for its part confirming 80 p. 100 of the clinically undeclared cases of thrombosis.", "contents": "[Incidence of deep venous thromboses in traumatology and methods of early detection]. In this work carried out at the Traumatology Centre in Strasbourg, out of 227 patients operated for a fracture situated between the pelvis and the tibial plateau, the authors endeavoured to show a thrombosis of the lower limbs. The means of exploration included in addition to the clinical and biological blood tests an isotopic, rheographic and phlebographic surveillance. The latter three ways of exploration are particularly viewed in this study, during which it was possible to demonstrate 44 p. 100 thrombo-embolic manifestations of which 38 p. 100 were detected only by the isotopic method, the phlebographic check for its part confirming 80 p. 100 of the clinically undeclared cases of thrombosis."}
{"id": "PMID:5935", "title": "Detection of mutant hemoglobins with altered affinity for oxygen. A simplified technique.", "content": "The detection of high- or low-affinity hemoglobins in subjects with polycythemia or anemia is difficult for most physicians because of the requirement for special equipment to do oxygen-hemoglobin dissociation curves. Measurement of the pH, oxygen tension, and oxygen saturation of antecubital venous blood with instruments present in most clinical chemistry laboratories permits an estimate of the strength of oxygen binding to hemoglobin. An equation can be used to convert the venous oxygen tension (standardized to pH 7.4) and the oxygen saturation to the P50 of the oxygen-hemoglobin dissociation curve on which the observed point falls. The data indicate that this method is a reliable initial step in the identification of a hemoglobin with abnormal affinity for oxygen and may be applied to population studies, since reliable results are obtained with venous blood stored at 4 degrees C for up to 24 hours.", "contents": "Detection of mutant hemoglobins with altered affinity for oxygen. A simplified technique. The detection of high- or low-affinity hemoglobins in subjects with polycythemia or anemia is difficult for most physicians because of the requirement for special equipment to do oxygen-hemoglobin dissociation curves. Measurement of the pH, oxygen tension, and oxygen saturation of antecubital venous blood with instruments present in most clinical chemistry laboratories permits an estimate of the strength of oxygen binding to hemoglobin. An equation can be used to convert the venous oxygen tension (standardized to pH 7.4) and the oxygen saturation to the P50 of the oxygen-hemoglobin dissociation curve on which the observed point falls. The data indicate that this method is a reliable initial step in the identification of a hemoglobin with abnormal affinity for oxygen and may be applied to population studies, since reliable results are obtained with venous blood stored at 4 degrees C for up to 24 hours."}
{"id": "PMID:5932", "title": "[Post-traumatic fat embolism of the hemorrhagic pulmonary edema type].", "content": "The authors present a case of post-traumatic fat embolus, which was remarkable by the very haemorrhagic nature of the pulmonary oedema, which healed without sequel.", "contents": "[Post-traumatic fat embolism of the hemorrhagic pulmonary edema type]. The authors present a case of post-traumatic fat embolus, which was remarkable by the very haemorrhagic nature of the pulmonary oedema, which healed without sequel."}
{"id": "PMID:5936", "title": "Antigenemia in fulminant pneumococcemia.", "content": "Two asplenic patients with fulminant pneumococcemia developed purpura and coagulopathy. Levels of C3 and C4 in the serum were low. Both patients had high levels of circulating capsular polysaccharide, and one patient had visible diplococci on a smear of the peripheral blood. Pneumococcal group C polysaccharide (C-substance) was detected in the serum of one of the patients. Possible pathogenetic relation of circulating pneumococcal antigens to the development of coagulopathy in pneumococcemia is discussed.", "contents": "Antigenemia in fulminant pneumococcemia. Two asplenic patients with fulminant pneumococcemia developed purpura and coagulopathy. Levels of C3 and C4 in the serum were low. Both patients had high levels of circulating capsular polysaccharide, and one patient had visible diplococci on a smear of the peripheral blood. Pneumococcal group C polysaccharide (C-substance) was detected in the serum of one of the patients. Possible pathogenetic relation of circulating pneumococcal antigens to the development of coagulopathy in pneumococcemia is discussed."}
{"id": "PMID:5933", "title": "[Acute tamponade: complication of resuscitation (cardiac perforation by a subclavian catheter)].", "content": "The authors report a case of acute tamponnade as result of the collection under pressure of a lipid solution in the pericardium following perforation of the right atrium by a sub-clavian catheter. Diagnosis and treatment were practically siumultaneous. Aspiration of the lipid solution (450 ml) via the catheter confirmed the diagnosis and successfully treated the problem. With regard to the case, the following are discussed: - diagnostic features of acute tamponnade (acetiological, clinical, heemodynamic, electrocardiographic and radiological signs); - the physiopathological mechanism of tamponnade with changes in intra-pericardiac and ventricular pressure/volume cures; - finally, the management of tamponnade.", "contents": "[Acute tamponade: complication of resuscitation (cardiac perforation by a subclavian catheter)]. The authors report a case of acute tamponnade as result of the collection under pressure of a lipid solution in the pericardium following perforation of the right atrium by a sub-clavian catheter. Diagnosis and treatment were practically siumultaneous. Aspiration of the lipid solution (450 ml) via the catheter confirmed the diagnosis and successfully treated the problem. With regard to the case, the following are discussed: - diagnostic features of acute tamponnade (acetiological, clinical, heemodynamic, electrocardiographic and radiological signs); - the physiopathological mechanism of tamponnade with changes in intra-pericardiac and ventricular pressure/volume cures; - finally, the management of tamponnade."}
{"id": "PMID:5938", "title": "RNA-protein interactions in alfalfa mosaic virus.", "content": "Particles of the bottom component of alfalfa mosaic virus have a compact bacilliform structure at neutral pH. When the pH is raised to 8.3 the structure unfolds. Since the particle weight does not change it is concluded that the protein subunits remain attached to the RNA. The particle weight of the spheroidal top component a of the virus is halved when the particles unfold at pH 8.3. This can be explained by the fact that these particles contain two RNA molecules of identical size. Free RNA molecules of alfalfa mosaic virus are able to withdraw protein subunits from intact particles of the virus. It is demonstrated that per RNA molecule there are a few sites with a high affinity for coat protein. Possibly these are the sites where the coat protein plays its role in activating the genome.", "contents": "RNA-protein interactions in alfalfa mosaic virus. Particles of the bottom component of alfalfa mosaic virus have a compact bacilliform structure at neutral pH. When the pH is raised to 8.3 the structure unfolds. Since the particle weight does not change it is concluded that the protein subunits remain attached to the RNA. The particle weight of the spheroidal top component a of the virus is halved when the particles unfold at pH 8.3. This can be explained by the fact that these particles contain two RNA molecules of identical size. Free RNA molecules of alfalfa mosaic virus are able to withdraw protein subunits from intact particles of the virus. It is demonstrated that per RNA molecule there are a few sites with a high affinity for coat protein. Possibly these are the sites where the coat protein plays its role in activating the genome."}
{"id": "PMID:5939", "title": "Human enolase isozymes: electrophoretic and biochemical evidence for three loci.", "content": "1. Four major enolase isozymes have been identified in human tissues and are referred to as L, M, 'intermediate' and 'fast'. The M isozyme is the major form found in skeletal muscle and heart extracts and the L isozyme the major form found in extracts of liver and most other tissues. The 'intermediate' and 'fast' isozymes are most active in brain but are observed as weak components in most other tissues including heart but are not seen in skeletal muscle. It was observed that during fetal development of heart and skeletal muscle the L form declines in activity while the M form increases in activity. 2. The kinetic properties, heat stabilities and molecular sizes of the main enolase isozymes have been compared. Although the isozymes share many features in common, the 'fast' isozyme is more stable when subjected to heat treatment than either the L or M isozymes. Further, the 'fast' isozyme retains its dimeric structure and activity in the absence of magnesium ions while the L and M isozymes dissociate and lose activity. The 'intermediate' isozyme has properties which are intermediate to those of the L and 'fast' isozymes. 3. The 'intermediate' isozyme can be partially dissociated to equal quantities of L and 'fast' isozymes by storage at room temperature or by freezing and thawing in the presence of 2 M-NaCl. Conversely, mixtures of L with 'fast' and M with 'fast' give rise to an 'intermediate' isozyme after freezing and thawing. 4. Evidence derived from this study has led to the suggestion that three separate gene loci are involved in the determination of human enolase. It is proposed that one of these, ENO1, determines the L isozyme which is the homodimer alphaalpha; another locus, ENO2, determines the 'fast' isozyme which is the homodiner betabeta; and the third locus, ENO3, determines the M isozyme which is the homodimer gammagamma. The 'intermediate' isozyme seen as a strong component in brain and as a weak component in most other tissues is thought to be the heterodimer alphabeta. In heart however it is probably mainly betagamma.", "contents": "Human enolase isozymes: electrophoretic and biochemical evidence for three loci. 1. Four major enolase isozymes have been identified in human tissues and are referred to as L, M, 'intermediate' and 'fast'. The M isozyme is the major form found in skeletal muscle and heart extracts and the L isozyme the major form found in extracts of liver and most other tissues. The 'intermediate' and 'fast' isozymes are most active in brain but are observed as weak components in most other tissues including heart but are not seen in skeletal muscle. It was observed that during fetal development of heart and skeletal muscle the L form declines in activity while the M form increases in activity. 2. The kinetic properties, heat stabilities and molecular sizes of the main enolase isozymes have been compared. Although the isozymes share many features in common, the 'fast' isozyme is more stable when subjected to heat treatment than either the L or M isozymes. Further, the 'fast' isozyme retains its dimeric structure and activity in the absence of magnesium ions while the L and M isozymes dissociate and lose activity. The 'intermediate' isozyme has properties which are intermediate to those of the L and 'fast' isozymes. 3. The 'intermediate' isozyme can be partially dissociated to equal quantities of L and 'fast' isozymes by storage at room temperature or by freezing and thawing in the presence of 2 M-NaCl. Conversely, mixtures of L with 'fast' and M with 'fast' give rise to an 'intermediate' isozyme after freezing and thawing. 4. Evidence derived from this study has led to the suggestion that three separate gene loci are involved in the determination of human enolase. It is proposed that one of these, ENO1, determines the L isozyme which is the homodimer alphaalpha; another locus, ENO2, determines the 'fast' isozyme which is the homodiner betabeta; and the third locus, ENO3, determines the M isozyme which is the homodimer gammagamma. The 'intermediate' isozyme seen as a strong component in brain and as a weak component in most other tissues is thought to be the heterodimer alphabeta. In heart however it is probably mainly betagamma."}
{"id": "PMID:5940", "title": "Adenylate kinases in man: evidence for a third locus.", "content": "The tissue distribution of the adenylate kinase isozymes in man has been examined using various substrates. The isozymes attributable to the AK1 and AK2 loci were identified, and an additional set of isozymes probably attributable to a third locus was also found. This locus has been provisionally designated AK3. The AK3 isozymes show activity with either GTP + AMP or ITP + AMP but do not show activity with ATP + AMP. They also differ from the AK1 and AK2 isozymes in electrophoretic mobility and from the AK1 isozymes in being resistant to silver inhibition. They are similar in molecular size to the AK1 isozymes whereas the AK2 isozymes are apparently larger. The AK3 isozymes evidently correspond to the enzyme nucleosidetriphosphate-adenylate kinase (2.7.4.10). Somatic cell hybrid studies indicate that the AK3 locus is not syntenic with that of AK2 (chromosome 1). The AK3 locus is however, probably syntenic with the AK1 locus, on chromosome 9. Genetically determined variation of AK3 has not been seen in a survey of about 80 individuals.", "contents": "Adenylate kinases in man: evidence for a third locus. The tissue distribution of the adenylate kinase isozymes in man has been examined using various substrates. The isozymes attributable to the AK1 and AK2 loci were identified, and an additional set of isozymes probably attributable to a third locus was also found. This locus has been provisionally designated AK3. The AK3 isozymes show activity with either GTP + AMP or ITP + AMP but do not show activity with ATP + AMP. They also differ from the AK1 and AK2 isozymes in electrophoretic mobility and from the AK1 isozymes in being resistant to silver inhibition. They are similar in molecular size to the AK1 isozymes whereas the AK2 isozymes are apparently larger. The AK3 isozymes evidently correspond to the enzyme nucleosidetriphosphate-adenylate kinase (2.7.4.10). Somatic cell hybrid studies indicate that the AK3 locus is not syntenic with that of AK2 (chromosome 1). The AK3 locus is however, probably syntenic with the AK1 locus, on chromosome 9. Genetically determined variation of AK3 has not been seen in a survey of about 80 individuals."}
{"id": "PMID:5942", "title": "[Criteria for evaluating calcium carbonate from the point of view of chlortetracycline biosynthesis].", "content": "Calcium carbonate is added to fermentation media in biosynthesis of tetracyclines for providing definite pH values and binding tetracycline into insoluble complexes. Seven different samples were studied with respect to their physical properties, such as the microscopic size of the particles, their form, capacity for agglomeration, specific volume, rate of the particle precipitation and chemical properties, such as purity, buffer capacity, effect on the medium pH before and after sterilization. The above properties were studied in comparison with activity chlortetracycline biosynthesis. Microfine calcium carbonate proved to be the best from the point of view of productivity of Str. aureofaciens. With its use the activity of the culture fluid increased by 20 per cent as compared to the other samples. The titration curve of the sample had the lowest bend.", "contents": "[Criteria for evaluating calcium carbonate from the point of view of chlortetracycline biosynthesis]. Calcium carbonate is added to fermentation media in biosynthesis of tetracyclines for providing definite pH values and binding tetracycline into insoluble complexes. Seven different samples were studied with respect to their physical properties, such as the microscopic size of the particles, their form, capacity for agglomeration, specific volume, rate of the particle precipitation and chemical properties, such as purity, buffer capacity, effect on the medium pH before and after sterilization. The above properties were studied in comparison with activity chlortetracycline biosynthesis. Microfine calcium carbonate proved to be the best from the point of view of productivity of Str. aureofaciens. With its use the activity of the culture fluid increased by 20 per cent as compared to the other samples. The titration curve of the sample had the lowest bend."}
{"id": "PMID:5943", "title": "[Study of the penicillin amidase from E. coli. An ultrasonic method of studying the ph- and temperature-conformational transitions in the active center of the enzyme].", "content": "pH and temperature conformation transitions in the active center of penicillin amidase i.e. penicillinamidohydrolase E.C. 3.5.I.II were investigated by means of the kinetic method and a new ultrasonic method. It was shown that the catalytic activity of the enzyme was controlled by 2 ionogenic groups with pK 6.1 and 10.2. The study of penicillinamidase by means of the ultrasonic method showed that the ionogenic group with pK 10 was responsible for maintaining the catalytically active conformation of the enzyme active center. Investigation of the temperature relation between the kinetic parameters of the enzymatic hydrolysis of benzylpenicillin catalyzed by penicillin amidase and the data on the effect of ultrasound on the enzyme showed that the enzyme was subjected to the temperature conformation transiton. The temperature and thermodynamic parameters of the conformation transition were determinded (T=318 degrees K, delta H=81 kcal/mole and delta S=255 e.u.). The structure of the active center of the enzyme is discussed on the basis of the data obtained.", "contents": "[Study of the penicillin amidase from E. coli. An ultrasonic method of studying the ph- and temperature-conformational transitions in the active center of the enzyme]. pH and temperature conformation transitions in the active center of penicillin amidase i.e. penicillinamidohydrolase E.C. 3.5.I.II were investigated by means of the kinetic method and a new ultrasonic method. It was shown that the catalytic activity of the enzyme was controlled by 2 ionogenic groups with pK 6.1 and 10.2. The study of penicillinamidase by means of the ultrasonic method showed that the ionogenic group with pK 10 was responsible for maintaining the catalytically active conformation of the enzyme active center. Investigation of the temperature relation between the kinetic parameters of the enzymatic hydrolysis of benzylpenicillin catalyzed by penicillin amidase and the data on the effect of ultrasound on the enzyme showed that the enzyme was subjected to the temperature conformation transiton. The temperature and thermodynamic parameters of the conformation transition were determinded (T=318 degrees K, delta H=81 kcal/mole and delta S=255 e.u.). The structure of the active center of the enzyme is discussed on the basis of the data obtained."}
{"id": "PMID:5945", "title": "[Chromatographic control of the process of rifamycin B isolation and purification].", "content": "A method of chromatography in a thin layer of Silica Cel No. 2 was developed for rifamicin B, rifamicin complex and some admixtures. Extracts of rifamicin B in an organic solvent, aqueous buffer reextracts and dry preparations of rifamicin B were analyzed with the above method. A half-quantitative chromatographic procedure for estimation of the main admixture in dry preparations was proposed.", "contents": "[Chromatographic control of the process of rifamycin B isolation and purification]. A method of chromatography in a thin layer of Silica Cel No. 2 was developed for rifamicin B, rifamicin complex and some admixtures. Extracts of rifamicin B in an organic solvent, aqueous buffer reextracts and dry preparations of rifamicin B were analyzed with the above method. A half-quantitative chromatographic procedure for estimation of the main admixture in dry preparations was proposed."}
{"id": "PMID:5941", "title": "Regulatory mast cells. I Suppressive action of their products on an in vitro primary immune reaction.", "content": "Products of mast cell degranulation, as well as histamine and serotonin, were added to a Mishell and Dutton preparation for in vitro primary immunisation (induction of IgM antibody formation) to sheep or horse red blood cells. Degranulation products were either obatined beforehand by reacting passively sensitised mast cells with the corresponding antigen (unrelated to or identical with the in vitro immunising antigen) or liberated into the culture medium where mast cells actively sensitised to the in vitro immunising antigen had been added. A 46 to 72 % reduction of direct (IgM) plaque forming cells was observed in all cases. This reduction was prevented by anti-histamine. The responsible mediators were active in the 0 to 24 hour period after antigen introduction. The anaphylactic degranulating antibodies triggering this inhibitory activity were found to be thermolabile in one experiment. An in vivo-induced mast cell degranulation led to a reduced formation of plaque forming cells. The enhancing and immunoregulatory activity of anaphylactic mouse antibodies is therefore tentatively and at least partially attributed to their capacity to degranulate mast cells after contact with the antigen.", "contents": "Regulatory mast cells. I Suppressive action of their products on an in vitro primary immune reaction. Products of mast cell degranulation, as well as histamine and serotonin, were added to a Mishell and Dutton preparation for in vitro primary immunisation (induction of IgM antibody formation) to sheep or horse red blood cells. Degranulation products were either obatined beforehand by reacting passively sensitised mast cells with the corresponding antigen (unrelated to or identical with the in vitro immunising antigen) or liberated into the culture medium where mast cells actively sensitised to the in vitro immunising antigen had been added. A 46 to 72 % reduction of direct (IgM) plaque forming cells was observed in all cases. This reduction was prevented by anti-histamine. The responsible mediators were active in the 0 to 24 hour period after antigen introduction. The anaphylactic degranulating antibodies triggering this inhibitory activity were found to be thermolabile in one experiment. An in vivo-induced mast cell degranulation led to a reduced formation of plaque forming cells. The enhancing and immunoregulatory activity of anaphylactic mouse antibodies is therefore tentatively and at least partially attributed to their capacity to degranulate mast cells after contact with the antigen."}
{"id": "PMID:5946", "title": "[Relationship between the antibacterial activity and the acceptor properties of certain penicillins].", "content": "Antibacterial activity of 2 natural and 12 semisynthetic penicillins against 5 strains of grampositive bacteria was determined and quantum chemical estimation of their molecules was performed with the Hukkel method. The data were indicative of the fact that antibacterial activity of the penicillins was connected with the acceptor properties of their molecules.", "contents": "[Relationship between the antibacterial activity and the acceptor properties of certain penicillins]. Antibacterial activity of 2 natural and 12 semisynthetic penicillins against 5 strains of grampositive bacteria was determined and quantum chemical estimation of their molecules was performed with the Hukkel method. The data were indicative of the fact that antibacterial activity of the penicillins was connected with the acceptor properties of their molecules."}
{"id": "PMID:5947", "title": "[Effect of different factors on the rate of benzylpenicillin conversion in an aqueous system-butylacetate system].", "content": "It was shown that the mass-transfer coefficient of non-dissociated benzylpenicillin during extraction was more than 1000 times higher than that during reextraction. For the latter it was found that the aqueous phase exerted limiting resistance during mass-transfer of benzylpenicillin. The effect of a number of factors on the kinetics was shown. These factors were the following: hydrodynamic conditions, temperature, pH of the aqueous phase.", "contents": "[Effect of different factors on the rate of benzylpenicillin conversion in an aqueous system-butylacetate system]. It was shown that the mass-transfer coefficient of non-dissociated benzylpenicillin during extraction was more than 1000 times higher than that during reextraction. For the latter it was found that the aqueous phase exerted limiting resistance during mass-transfer of benzylpenicillin. The effect of a number of factors on the kinetics was shown. These factors were the following: hydrodynamic conditions, temperature, pH of the aqueous phase."}
{"id": "PMID:5948", "title": "[Regulation of tetracycline biosynthesis by controlling the growth of the producer].", "content": "Regulation of the rate growth of Act. aureofaciens in batch fermentation by maintaining the concentrations of phosphorus, ammonium nitrogen, glucose and pH values at the levels favourable for intensive growth at the beginning of the process and after accumulation of the biomass at the levels optimal for retarded growth of the organism resulted in significant prolongation of the period of intensive antibiotic production, i.e. intensification of the fermentation process. Microscopic investigation of the organism development under conditions of regulated fermentation revealed the presence of significant amounts of free peripheral highly basophilic hyphae for a prolonged period of time. The hyphae possessed a capacity for growth and intensive metabolism unlike the control culture which was liable to early autolysis.", "contents": "[Regulation of tetracycline biosynthesis by controlling the growth of the producer]. Regulation of the rate growth of Act. aureofaciens in batch fermentation by maintaining the concentrations of phosphorus, ammonium nitrogen, glucose and pH values at the levels favourable for intensive growth at the beginning of the process and after accumulation of the biomass at the levels optimal for retarded growth of the organism resulted in significant prolongation of the period of intensive antibiotic production, i.e. intensification of the fermentation process. Microscopic investigation of the organism development under conditions of regulated fermentation revealed the presence of significant amounts of free peripheral highly basophilic hyphae for a prolonged period of time. The hyphae possessed a capacity for growth and intensive metabolism unlike the control culture which was liable to early autolysis."}
{"id": "PMID:5949", "title": "[Study of the biosynthesis of a carbohydrate fragment of rubomycin].", "content": "When the rubomycin-producing organism was grown in the presence of an evenly labeled C14-glucose and various non-labeled carbon sources, the carbohydrate part of the antibiotic also became evently labeled. The activity of I carbon atom of rubomycin sugar grown against the background of non-labeled glycerol was almost 3 times higher than the respective value of the aglycone activity. C14-acetate, C14-propionate, C14-methionine and daunosamine were not incorporated. The data are indicative of the fact that there was no splitting of the glucose carbon skeleton during conversion of glucose into amino sugar.", "contents": "[Study of the biosynthesis of a carbohydrate fragment of rubomycin]. When the rubomycin-producing organism was grown in the presence of an evenly labeled C14-glucose and various non-labeled carbon sources, the carbohydrate part of the antibiotic also became evently labeled. The activity of I carbon atom of rubomycin sugar grown against the background of non-labeled glycerol was almost 3 times higher than the respective value of the aglycone activity. C14-acetate, C14-propionate, C14-methionine and daunosamine were not incorporated. The data are indicative of the fact that there was no splitting of the glucose carbon skeleton during conversion of glucose into amino sugar."}
{"id": "PMID:5950", "title": "[Physicochemical properties of 7-phenylacetamidodesacetoxy-cephalosporanic acid].", "content": "7-phenylacetamidodesacetoxycephalosporanic acid was prepared by transformation of benzylpenicillin. The acid was subjected to potentiometric titration and investigation of its electrophoretic mobility at wide pH ranges. The data of the potentiometric titration and electrophoresis were used for calculation of the acid ionization constant. Minimum solubility of the acid was determined and the curve of its solubility at wide pH ranges was estimated.", "contents": "[Physicochemical properties of 7-phenylacetamidodesacetoxy-cephalosporanic acid]. 7-phenylacetamidodesacetoxycephalosporanic acid was prepared by transformation of benzylpenicillin. The acid was subjected to potentiometric titration and investigation of its electrophoretic mobility at wide pH ranges. The data of the potentiometric titration and electrophoresis were used for calculation of the acid ionization constant. Minimum solubility of the acid was determined and the curve of its solubility at wide pH ranges was estimated."}
{"id": "PMID:5951", "title": "Beta-glucosidase of Trichoderma: its biosynthesis and role in saccharification of cellulose.", "content": "The extracellular beta-glucosidase of Trichoderma viride generally is present in low levels when the organism is cultured on cellulose because it is inactivated under the acid conditions which develop in the medium while the other enzymes of the cellulase complex are more stable. With the appropriate pH control, inactivation of beta-glucosidase is prevented and the activity of this enzyme increases during growth. In the saccharification of crystalline cellulose, or of cellulose at low concentrations, much of the glucose produced is the result of the cleavage of cellobiose by beta-glucosidase. However when high concentrations (10%) of pretreated cellulose are saccharified, significant quantities of glucose are produced by action of enzymes other than beta-glucosidase.", "contents": "Beta-glucosidase of Trichoderma: its biosynthesis and role in saccharification of cellulose. The extracellular beta-glucosidase of Trichoderma viride generally is present in low levels when the organism is cultured on cellulose because it is inactivated under the acid conditions which develop in the medium while the other enzymes of the cellulase complex are more stable. With the appropriate pH control, inactivation of beta-glucosidase is prevented and the activity of this enzyme increases during growth. In the saccharification of crystalline cellulose, or of cellulose at low concentrations, much of the glucose produced is the result of the cleavage of cellobiose by beta-glucosidase. However when high concentrations (10%) of pretreated cellulose are saccharified, significant quantities of glucose are produced by action of enzymes other than beta-glucosidase."}
{"id": "PMID:5952", "title": "Growth of Fusarium moniliforme on carob aqueous extract and nutritional evaluation of its biomass.", "content": "Fusarium moniliforme was cultured semicontinuously on a carob medium in a 14-liter fermentor (8.5-liter working volume). The growth medium provided 2.4% carob sugar, 0.72% NH4H2PO4, and 0.03% MgSO4-7H2O. The biomass harvest was 8.8 g/liter per day. Ninety percent of the sugars were consumed, and the pH dropped from 5.9 to about 3.7. The crude protein (N X 6.25) of the spray-dried mycelium was 380 g/kg, 300 g/kg for the true protein (Lowry), and 4.8 g/kg for the (Folin-Denis) tannic acid. The mycelium was evaluated nutritionally with the weanling rat as experimental animal. The protein efficiency ratio and net protein utilization values for the unsupplemented mycelium were 1.15 and 0.42, respectively, and for the mycelium supplemented with DL-methionine (5 g/kg) they were 2.31 and 0.72, respectively. No growth depression was observed in the experimental rats, and on dissection of the carcasses the internal organs were found to be normal.", "contents": "Growth of Fusarium moniliforme on carob aqueous extract and nutritional evaluation of its biomass. Fusarium moniliforme was cultured semicontinuously on a carob medium in a 14-liter fermentor (8.5-liter working volume). The growth medium provided 2.4% carob sugar, 0.72% NH4H2PO4, and 0.03% MgSO4-7H2O. The biomass harvest was 8.8 g/liter per day. Ninety percent of the sugars were consumed, and the pH dropped from 5.9 to about 3.7. The crude protein (N X 6.25) of the spray-dried mycelium was 380 g/kg, 300 g/kg for the true protein (Lowry), and 4.8 g/kg for the (Folin-Denis) tannic acid. The mycelium was evaluated nutritionally with the weanling rat as experimental animal. The protein efficiency ratio and net protein utilization values for the unsupplemented mycelium were 1.15 and 0.42, respectively, and for the mycelium supplemented with DL-methionine (5 g/kg) they were 2.31 and 0.72, respectively. No growth depression was observed in the experimental rats, and on dissection of the carcasses the internal organs were found to be normal."}
{"id": "PMID:5953", "title": "Incorporation of proline into prodigiosin by a Put mutant of Serratia marcesens.", "content": "A Put mutant of Serratia marcescens, deficient in proline oxidase and therefore unable to degrade proline, was used to assay for an enzymatic reaction responsible for incorporation of proline into prodigiosin. The reaction had a pH optimum of 7.5 and a Km of 1.1 X 10(-4) M at 27 C. At temperatures above 27 C, the velocity of the reaction decreased with increasing temperature and little activity was detected at 42 C. Activity of the enzyme was directly proportional to the quantity of pigment formed and was inhibited by thioproline, a substrate analog. These data suggested the presence of a unique and specific enzyme in the biosynthetic pathway for prodigiosin.", "contents": "Incorporation of proline into prodigiosin by a Put mutant of Serratia marcesens. A Put mutant of Serratia marcescens, deficient in proline oxidase and therefore unable to degrade proline, was used to assay for an enzymatic reaction responsible for incorporation of proline into prodigiosin. The reaction had a pH optimum of 7.5 and a Km of 1.1 X 10(-4) M at 27 C. At temperatures above 27 C, the velocity of the reaction decreased with increasing temperature and little activity was detected at 42 C. Activity of the enzyme was directly proportional to the quantity of pigment formed and was inhibited by thioproline, a substrate analog. These data suggested the presence of a unique and specific enzyme in the biosynthetic pathway for prodigiosin."}
{"id": "PMID:5954", "title": "Enzymatic conversion of sterigmatocystin into aflatoxin B1 by cell-free extracts of Aspergillus parasiticus.", "content": "A cell-free extract, prepared from Aspergillus parasiticus ATCC 15517 grown in synthetic medium, was active in converting [14C]sterigmatocystin into aflatoxin B1 in the presence of reduced nicotinamide adenine dinucleotide phosphate. The activity was demonstrated by the time course of conversion and the linear dependence of the yield of product on enzyme concentrations. Optimum activity was obtained at pH 7.5 to 7.8 at 27 C. The results confirm sterigmatocystin as a biogenetic precursor of aflatoxin B1. Techniques were developed for enzymatic studies on aflatoxin biosynthesis.", "contents": "Enzymatic conversion of sterigmatocystin into aflatoxin B1 by cell-free extracts of Aspergillus parasiticus. A cell-free extract, prepared from Aspergillus parasiticus ATCC 15517 grown in synthetic medium, was active in converting [14C]sterigmatocystin into aflatoxin B1 in the presence of reduced nicotinamide adenine dinucleotide phosphate. The activity was demonstrated by the time course of conversion and the linear dependence of the yield of product on enzyme concentrations. Optimum activity was obtained at pH 7.5 to 7.8 at 27 C. The results confirm sterigmatocystin as a biogenetic precursor of aflatoxin B1. Techniques were developed for enzymatic studies on aflatoxin biosynthesis."}
{"id": "PMID:5963", "title": "Cord gamma glutamyl transpeptidase activity and neonatal jaundice.", "content": "gamma Glutamyl transpeptidase (GGT) activity was measured in normal neonates and in maternal serum post partum. Levels were above the normal adult range (35I U/1) in all neonates and a significant correlation was bound between enzyme activity and bilirubin levels on day 7(P less than 0-005). The mean bilirubin level on days 4 and 7 was higher in babies with cord values less than 90 IU/1. In certain circumstances increased plasma GGT activity may serve as an index of enzyme induction. However, our results suggest that raised levels in the neonate may reflect hepatic microsomal damage with subsequent impairment of bilirubin conjugation. Further evaluative studies of cord GGT activity in neonates at risk, with a view to early prophylactic or therapeutic measures, are indicated.", "contents": "Cord gamma glutamyl transpeptidase activity and neonatal jaundice. gamma Glutamyl transpeptidase (GGT) activity was measured in normal neonates and in maternal serum post partum. Levels were above the normal adult range (35I U/1) in all neonates and a significant correlation was bound between enzyme activity and bilirubin levels on day 7(P less than 0-005). The mean bilirubin level on days 4 and 7 was higher in babies with cord values less than 90 IU/1. In certain circumstances increased plasma GGT activity may serve as an index of enzyme induction. However, our results suggest that raised levels in the neonate may reflect hepatic microsomal damage with subsequent impairment of bilirubin conjugation. Further evaluative studies of cord GGT activity in neonates at risk, with a view to early prophylactic or therapeutic measures, are indicated."}
{"id": "PMID:5964", "title": "Cardiorespiratory response to feeding in newborn infants.", "content": "Milk feeds were given through indwelling nasogastric tubes to 14 infants with respiratory distress. Similar cardiorespiratory disturbances were observed when the infants were fed (5 ml/kg per feed) human milk, cow's mild, or distilled water. Pao2 fell after a feed but recovered to the prefeed  value at 30 minutes, at which time Paco2 had fallen and the respiratory rate had increased. No changes in pH, heart rate, or blood pressure were observed. Portal sinus pressures rose after feeding in association with an increase in central venous pressure. In contrast, when the ill infants were fed human milk at a volume of 2-5 ml/kg per feed no consistent changes in any of the measurements were found. These studies suggested that the cardiorespiratory effects were related to volume displacement resulting from feeds being introduced into the stomach. The relation of the increase in central venous pressure and the magnitude and direction of shunting in infants with the respiratory distress syndrome is uncertain. Adverse effects may be avoided by giving smaller, and therefore even more frequent, feeds.", "contents": "Cardiorespiratory response to feeding in newborn infants. Milk feeds were given through indwelling nasogastric tubes to 14 infants with respiratory distress. Similar cardiorespiratory disturbances were observed when the infants were fed (5 ml/kg per feed) human milk, cow's mild, or distilled water. Pao2 fell after a feed but recovered to the prefeed  value at 30 minutes, at which time Paco2 had fallen and the respiratory rate had increased. No changes in pH, heart rate, or blood pressure were observed. Portal sinus pressures rose after feeding in association with an increase in central venous pressure. In contrast, when the ill infants were fed human milk at a volume of 2-5 ml/kg per feed no consistent changes in any of the measurements were found. These studies suggested that the cardiorespiratory effects were related to volume displacement resulting from feeds being introduced into the stomach. The relation of the increase in central venous pressure and the magnitude and direction of shunting in infants with the respiratory distress syndrome is uncertain. Adverse effects may be avoided by giving smaller, and therefore even more frequent, feeds."}
{"id": "PMID:5971", "title": "Clinical experience with the Teflo disposable membrane oxygenator.", "content": "A simple, inexpensive, highly efficient disposable membrane oxygenator with low priming volume and a microporous membrane recently has become available. Animal and clinical investigations of its use have been most satisfactory, and clinical experience now has been extended to include 285 patients. Its primary advantage has been the ability to control oxygenation and carbon dioxide separately. Disadvantages have included the somewhat increased complexity of the system as compared with bubble oxygenator systems, the necessity of converting pumps for its use, and excessive condensation of water vapor in the gas phase of the oxygenator unless certain precautions are followed.", "contents": "Clinical experience with the Teflo disposable membrane oxygenator. A simple, inexpensive, highly efficient disposable membrane oxygenator with low priming volume and a microporous membrane recently has become available. Animal and clinical investigations of its use have been most satisfactory, and clinical experience now has been extended to include 285 patients. Its primary advantage has been the ability to control oxygenation and carbon dioxide separately. Disadvantages have included the somewhat increased complexity of the system as compared with bubble oxygenator systems, the necessity of converting pumps for its use, and excessive condensation of water vapor in the gas phase of the oxygenator unless certain precautions are followed."}
{"id": "PMID:5972", "title": "Hypothermia and rewarming by peritoneal dialysis and temperature-controlled inhalate.", "content": "In 12 rabbits hypothermia and rewarming were induced with temperature-controlled circulating peritoneal dialysis in combination with temperature-controlled hypoxic and hypercapnic gas mixtures. The average cooling time necessary for the esophageal temperature to decrease from 37.7 degrees +/- 0.7 to 20.6 degrees +/- 1.0 degrees C was 81 +/- 34 minutes with a range of 41 to 150 minutes. The average warming time for esophageal temperature to increase from 20.6 degrees +/- 1.0 degrees C to 35.2 degrees +/- 1.8 degrees C was 90 +/- 35 minutes. Time of cooling was related to the proportions of inspired carbon dioxide and oxygen. In contrast to surface and bypass methods, esophageal and muscular temperatures agreed very closely, suggesting an absence of regional temperature gradients.", "contents": "Hypothermia and rewarming by peritoneal dialysis and temperature-controlled inhalate. In 12 rabbits hypothermia and rewarming were induced with temperature-controlled circulating peritoneal dialysis in combination with temperature-controlled hypoxic and hypercapnic gas mixtures. The average cooling time necessary for the esophageal temperature to decrease from 37.7 degrees +/- 0.7 to 20.6 degrees +/- 1.0 degrees C was 81 +/- 34 minutes with a range of 41 to 150 minutes. The average warming time for esophageal temperature to increase from 20.6 degrees +/- 1.0 degrees C to 35.2 degrees +/- 1.8 degrees C was 90 +/- 35 minutes. Time of cooling was related to the proportions of inspired carbon dioxide and oxygen. In contrast to surface and bypass methods, esophageal and muscular temperatures agreed very closely, suggesting an absence of regional temperature gradients."}
{"id": "PMID:5973", "title": "Angioplastic repair of a ruptured pulmonary artery aneurysm.", "content": "A 28-year-old woman had a ruptured solitary pulmonary arterial aneurysm which was successfully treated by pericardial patch graft. The etiology of the aneurysm could not be determined although the patient had had several episodes of blunt chest trauma in the past. Unusual aspects of this case include: location of the aneurysm in the intermediate portion of the left pulmonary artery within the major intralobar fissure, intrapleural rupture, preoperative diagnosis by pulmonary angiography, and an incidentally discovered histopathological abnormality of the aneurysm itself for which no satisfactory explanation has been found.", "contents": "Angioplastic repair of a ruptured pulmonary artery aneurysm. A 28-year-old woman had a ruptured solitary pulmonary arterial aneurysm which was successfully treated by pericardial patch graft. The etiology of the aneurysm could not be determined although the patient had had several episodes of blunt chest trauma in the past. Unusual aspects of this case include: location of the aneurysm in the intermediate portion of the left pulmonary artery within the major intralobar fissure, intrapleural rupture, preoperative diagnosis by pulmonary angiography, and an incidentally discovered histopathological abnormality of the aneurysm itself for which no satisfactory explanation has been found."}
{"id": "PMID:5974", "title": "Suppression of renin release by timolol.", "content": "The beta-adrenergic blocking agent, timolol, administered to resting rabbits as an i.v. bolus (0.125 mg/kg) sustained by a 2-hr infusion at 0.0625 mg/kg/hr, caused significant depression of plasma renin activity (PRA) to 49% of the control level. Significant correlations emerged between the fall in mean blood pressure and changes in both heart rate and PRA. Timolol also antagonized isoprenaline-induced renin release. In anaesthetized normal rats, timolol (0.2 mg/kg i.p.) suppressed mean plasma renin concentration (PRC) to 16% of the pre-treatment value. Furthermore, the mean PRC of normal rats, bled immediately after decapitation, to avoid stimulating renin secretion, was reduced by 55% one hr after i.p. injection of timolol. The potency of timolol in this respect was 8 times that of dl-propranolol. Thus, in rabbits and rats, timolol effectively depresses both basal and stimulated plasma renin levels.", "contents": "Suppression of renin release by timolol. The beta-adrenergic blocking agent, timolol, administered to resting rabbits as an i.v. bolus (0.125 mg/kg) sustained by a 2-hr infusion at 0.0625 mg/kg/hr, caused significant depression of plasma renin activity (PRA) to 49% of the control level. Significant correlations emerged between the fall in mean blood pressure and changes in both heart rate and PRA. Timolol also antagonized isoprenaline-induced renin release. In anaesthetized normal rats, timolol (0.2 mg/kg i.p.) suppressed mean plasma renin concentration (PRC) to 16% of the pre-treatment value. Furthermore, the mean PRC of normal rats, bled immediately after decapitation, to avoid stimulating renin secretion, was reduced by 55% one hr after i.p. injection of timolol. The potency of timolol in this respect was 8 times that of dl-propranolol. Thus, in rabbits and rats, timolol effectively depresses both basal and stimulated plasma renin levels."}
{"id": "PMID:5975", "title": "Effect of sodium acetate infusion on renal function in the dog.", "content": "Sodium acetate (AC) is routinely used in dialysis solutions in hemodialysis units as it provides a ready source of fixed base. The renal dynamics of the buffer salt are not well known. Anesthetized dogs received i.v. infusions of AC at a rate of 40 to 600 muEq/kg/min. Urinary AC and bicarbonate excretion was measured and correlated with PAH and creatinine clearance and urinary electrolyte excretion. AC appeared in the urine as quickly as it was detected in the plasma. Its excretion gradually increased and tended to parallel bicarbonate excretion. PAH clearance increased with the advent of AC infusion, plasma pH and bicarbonate increase as AC is introduced. AC infusion caused an immediate drop in blood pressure. The systolic blood pressure returned to control in 3-5 min; there was a more gradual return in diastolic pressure. We conclude that AC is filtered and excreted into the urine at low plasma levels and has a low renal threshold.", "contents": "Effect of sodium acetate infusion on renal function in the dog. Sodium acetate (AC) is routinely used in dialysis solutions in hemodialysis units as it provides a ready source of fixed base. The renal dynamics of the buffer salt are not well known. Anesthetized dogs received i.v. infusions of AC at a rate of 40 to 600 muEq/kg/min. Urinary AC and bicarbonate excretion was measured and correlated with PAH and creatinine clearance and urinary electrolyte excretion. AC appeared in the urine as quickly as it was detected in the plasma. Its excretion gradually increased and tended to parallel bicarbonate excretion. PAH clearance increased with the advent of AC infusion, plasma pH and bicarbonate increase as AC is introduced. AC infusion caused an immediate drop in blood pressure. The systolic blood pressure returned to control in 3-5 min; there was a more gradual return in diastolic pressure. We conclude that AC is filtered and excreted into the urine at low plasma levels and has a low renal threshold."}
{"id": "PMID:5976", "title": "Effects of intravenous anesthetics on continuous avoidance behavior in the rat.", "content": "The actions of ketamine, etoxadrol and thiopental on continuous avoidance behavior in the rat were evaluated following i.v. administration. Ketamine and thiopental exerted only a depressant effect on avoidance behavior which was attributable to the anesthetic properties of the drugs. In contrast, biphasic activity was displayed with etoxadrol; avoidance responding was increased at low doses and decreased at high doses. A persistent rebound stimulation of responding occurred upon recovery from the anesthetic effect of high doses of etoxadrol. The effects of these drugs on continuous avoidance behavior do not correlate with previously reported effects on the disposition of brain monaoamines.", "contents": "Effects of intravenous anesthetics on continuous avoidance behavior in the rat. The actions of ketamine, etoxadrol and thiopental on continuous avoidance behavior in the rat were evaluated following i.v. administration. Ketamine and thiopental exerted only a depressant effect on avoidance behavior which was attributable to the anesthetic properties of the drugs. In contrast, biphasic activity was displayed with etoxadrol; avoidance responding was increased at low doses and decreased at high doses. A persistent rebound stimulation of responding occurred upon recovery from the anesthetic effect of high doses of etoxadrol. The effects of these drugs on continuous avoidance behavior do not correlate with previously reported effects on the disposition of brain monaoamines."}
{"id": "PMID:5977", "title": "Drugs and PGO waves in the lateral geniculate body of the curarized cat. V. Miscellaneous compounds. Synopsis of the role of central neurotransmitters on PGO wave activity.", "content": "In the last part of this series we have studied the effects of various drugs on ponto-geniculo-occipital (PGO) waves induced by the benzoquinolizine derivative, Ro 4-1284 (PGO(1284)), and by the inhibitor of trypotophan hydroxylase, p-chlorophenylalanine (PGO(PCPA)), and continuously recorder and counted in the lateral geniculate bodies (LGB) of unanaesthetized and immobilizedcats. The major aim of this study was to test the specificity of drug-induced alterations of the PGO wave activity suggested by the previous investigations. Hypnotics-sedatives of different classes had no significant effects in doses that did not markedly alter the electrical background activity in the LGB. A notable exception was gamma-hydroxybutyric acid which increased the density of PGO(1284) and PGO(PCPA). A number of neuroleptics were found inactive; sulpiride surprisingly decreased the density of PGO(1284). Bulbocapnine had a similar effect. Convulsants in subconvulsive doses did not uniformly affect PGO waves; while pentetrazole had no consistent effect, strychnine decreased and picrotoxin increased the density of PGO(1284). High doses of morphine, methadone and meperidine decreased the PGO(1284). Ethanol was inactive even in high doses. Caffeine and mefexamide reduced the density of PGO(1284). Mepiprazol was the most potent depressant of PGO(1284, probably by inhibiting the uptake of 5-HT. Mescaline was a weak depressor of PGO(1284). p-Chloromethamphetamine induced PGO waves in untreated cats less consitently than did PCPA. Amantadine reduced the amplitude of PGO waves due to a central antinicotinic action. The results of this study and of the whole series suggested a tentative scheme of the generation and modulation of PGO waves, in which the hypothetical roles and sites of action of four central neurotransmitters are included.", "contents": "Drugs and PGO waves in the lateral geniculate body of the curarized cat. V. Miscellaneous compounds. Synopsis of the role of central neurotransmitters on PGO wave activity. In the last part of this series we have studied the effects of various drugs on ponto-geniculo-occipital (PGO) waves induced by the benzoquinolizine derivative, Ro 4-1284 (PGO(1284)), and by the inhibitor of trypotophan hydroxylase, p-chlorophenylalanine (PGO(PCPA)), and continuously recorder and counted in the lateral geniculate bodies (LGB) of unanaesthetized and immobilizedcats. The major aim of this study was to test the specificity of drug-induced alterations of the PGO wave activity suggested by the previous investigations. Hypnotics-sedatives of different classes had no significant effects in doses that did not markedly alter the electrical background activity in the LGB. A notable exception was gamma-hydroxybutyric acid which increased the density of PGO(1284) and PGO(PCPA). A number of neuroleptics were found inactive; sulpiride surprisingly decreased the density of PGO(1284). Bulbocapnine had a similar effect. Convulsants in subconvulsive doses did not uniformly affect PGO waves; while pentetrazole had no consistent effect, strychnine decreased and picrotoxin increased the density of PGO(1284). High doses of morphine, methadone and meperidine decreased the PGO(1284). Ethanol was inactive even in high doses. Caffeine and mefexamide reduced the density of PGO(1284). Mepiprazol was the most potent depressant of PGO(1284, probably by inhibiting the uptake of 5-HT. Mescaline was a weak depressor of PGO(1284). p-Chloromethamphetamine induced PGO waves in untreated cats less consitently than did PCPA. Amantadine reduced the amplitude of PGO waves due to a central antinicotinic action. The results of this study and of the whole series suggested a tentative scheme of the generation and modulation of PGO waves, in which the hypothetical roles and sites of action of four central neurotransmitters are included."}
{"id": "PMID:5978", "title": "Nitrogen fixation by hydrogen-utilizing bacteria.", "content": "Seventeen strains of nitrogen-fixing bacteria, isolated from different habitats on hydrogen and carbon dioxide as well as on other substrates, morphologically resembled each other. All strains, including Mycobacterium flavum 301, grew autotrophically with hydrogen. The isolate strain 6 was sensitive to oxygen when dependent on N2 as nitrogen source, a consequence of the sensitivity of its nitrogenase towards oxygen. At the same time, strain 6 was sensitive to hydrogen when growing autotrophically on N2 as nitrogen source, but hydrogen did not affect acetylene reduction by these cells.", "contents": "Nitrogen fixation by hydrogen-utilizing bacteria. Seventeen strains of nitrogen-fixing bacteria, isolated from different habitats on hydrogen and carbon dioxide as well as on other substrates, morphologically resembled each other. All strains, including Mycobacterium flavum 301, grew autotrophically with hydrogen. The isolate strain 6 was sensitive to oxygen when dependent on N2 as nitrogen source, a consequence of the sensitivity of its nitrogenase towards oxygen. At the same time, strain 6 was sensitive to hydrogen when growing autotrophically on N2 as nitrogen source, but hydrogen did not affect acetylene reduction by these cells."}
{"id": "PMID:5979", "title": "Isolation of a moderate halophilic ammonia-oxidizing bacterium, Nitrosococcus mobilis nov. sp.", "content": "An ammonia-oxidizing bacterium was isolated from a sample of brackish water (North Sea, Harbour of Husum). It is a motile large coccus 1.5-1.7 mum in diameter. The extensive cytomembrane system occurring as flattened vesicles in the peripheral region of the cytoplasm and as intrusions into the center of the cytoplasm is to be emphasized as a characteristic mark of identification. The lithoautotrophically growing bacterium turned out to be an obligate halophile. Because of its physiological and morphological properties, we assigned it to the genus Nitrosococcus and propose the name Nitrosococcus mobilis.", "contents": "Isolation of a moderate halophilic ammonia-oxidizing bacterium, Nitrosococcus mobilis nov. sp. An ammonia-oxidizing bacterium was isolated from a sample of brackish water (North Sea, Harbour of Husum). It is a motile large coccus 1.5-1.7 mum in diameter. The extensive cytomembrane system occurring as flattened vesicles in the peripheral region of the cytoplasm and as intrusions into the center of the cytoplasm is to be emphasized as a characteristic mark of identification. The lithoautotrophically growing bacterium turned out to be an obligate halophile. Because of its physiological and morphological properties, we assigned it to the genus Nitrosococcus and propose the name Nitrosococcus mobilis."}
{"id": "PMID:5980", "title": "An ammonia-oxidizing bacterium, Nitrosovibrio tenuis nov. gen. nov. sp.", "content": "An ammonia-oxidizing, autotroph growing, slender, curved rod was isolated from the soil of Hawaii. It is well distinguishable from any other nitrifying bacteria thus far described by their morphology. The cells are 1.1-3.0 mum long and 0.3-0.4 mum wide. They are motile by means of 1-4 subpolar to lateral flagella. In contrast to most of the ammonia-oxidizing bacteria the isolated vibrio is void of an extensive cytomembrane system. To categorize this not yet described species we propose to create the new genus Nitrosovibrio and to classify the isolated strain as Nitrosovibrio tenuis.", "contents": "An ammonia-oxidizing bacterium, Nitrosovibrio tenuis nov. gen. nov. sp. An ammonia-oxidizing, autotroph growing, slender, curved rod was isolated from the soil of Hawaii. It is well distinguishable from any other nitrifying bacteria thus far described by their morphology. The cells are 1.1-3.0 mum long and 0.3-0.4 mum wide. They are motile by means of 1-4 subpolar to lateral flagella. In contrast to most of the ammonia-oxidizing bacteria the isolated vibrio is void of an extensive cytomembrane system. To categorize this not yet described species we propose to create the new genus Nitrosovibrio and to classify the isolated strain as Nitrosovibrio tenuis."}
{"id": "PMID:5981", "title": "Properties of heterocysts isolated with colloidal silica.", "content": "A method is described for the isolation of heterocysts that are virtually free of contaminating cell debris after sonication of aerobically grown Anabaena 7120. Isolated heterocysts reduced acetylene in a light-dependent process in the absence of exogenously provided ATP; heterocysts supplied with ATP and Na2S2O4 reduced acetylene slowly in the dark but still showed a marked light activation. Nitrogenase activity was greatest in fractions containing intact heterocysts. Up to 13% of the activity of the intact filaments was accounted for in the isolated heterocyst preparation. Isolated heterocysts took up O2 in a light-independent process; O2 uptake with added NADP+ was enhanced by pyruvate, isocitrate and intermediates of the oxidative pentose pathway.", "contents": "Properties of heterocysts isolated with colloidal silica. A method is described for the isolation of heterocysts that are virtually free of contaminating cell debris after sonication of aerobically grown Anabaena 7120. Isolated heterocysts reduced acetylene in a light-dependent process in the absence of exogenously provided ATP; heterocysts supplied with ATP and Na2S2O4 reduced acetylene slowly in the dark but still showed a marked light activation. Nitrogenase activity was greatest in fractions containing intact heterocysts. Up to 13% of the activity of the intact filaments was accounted for in the isolated heterocyst preparation. Isolated heterocysts took up O2 in a light-independent process; O2 uptake with added NADP+ was enhanced by pyruvate, isocitrate and intermediates of the oxidative pentose pathway."}
{"id": "PMID:5982", "title": "Nitrogenase activity in cultured Rhizobium sp. strain 32H1: nutritional and physical considerations.", "content": "Nutritional and physical conditions affecting nitrogenase activity in the strain of \"cowpea\" rhizobia, 32H1, were examined using cultures grown on agar medium. Arabinose in the basic medium (CS7) could be replaced by ribose, xylose, or glycerol, but mannitol, glucose, sucrose, or galactose only supported low nitrogenase (C2H2 reduction) activity. Succinate could be replaced by pyruvate, fumarate, malate, or 2-oxoglutarate, but without any carboxylic acid, nitrogenase activity was low or undetectable unless a high level of arabinose was provided. Inositol was not essential. Several nitrogen sources could replace glutamine including glutamate, urea, (NH4)2SO4 and asparagine. The maximum nitrogenase activity of cultures grown in air at 30 degrees C was observed under assay conditions of pO2=0.20-0.25 atm and 30 degrees C incubation. Greatest activity occurred after a period of rapid bacterial growth, when viable cell count was relatively constant. Compared with results obtained on the CS7 medium, nitrogenase activity could be substantially increased and/or sustained for longer periods of time by using 12.5 MM succinate and 100 mM arabinose, by increasing phosphate concentration from 2 to 30-50 mM, or by culturing the bacteria at 25 degrees C.", "contents": "Nitrogenase activity in cultured Rhizobium sp. strain 32H1: nutritional and physical considerations. Nutritional and physical conditions affecting nitrogenase activity in the strain of \"cowpea\" rhizobia, 32H1, were examined using cultures grown on agar medium. Arabinose in the basic medium (CS7) could be replaced by ribose, xylose, or glycerol, but mannitol, glucose, sucrose, or galactose only supported low nitrogenase (C2H2 reduction) activity. Succinate could be replaced by pyruvate, fumarate, malate, or 2-oxoglutarate, but without any carboxylic acid, nitrogenase activity was low or undetectable unless a high level of arabinose was provided. Inositol was not essential. Several nitrogen sources could replace glutamine including glutamate, urea, (NH4)2SO4 and asparagine. The maximum nitrogenase activity of cultures grown in air at 30 degrees C was observed under assay conditions of pO2=0.20-0.25 atm and 30 degrees C incubation. Greatest activity occurred after a period of rapid bacterial growth, when viable cell count was relatively constant. Compared with results obtained on the CS7 medium, nitrogenase activity could be substantially increased and/or sustained for longer periods of time by using 12.5 MM succinate and 100 mM arabinose, by increasing phosphate concentration from 2 to 30-50 mM, or by culturing the bacteria at 25 degrees C."}
{"id": "PMID:5983", "title": "Ribulose biophosphate carboxylase from Thiobacillus A2. Its purification and properties.", "content": "Ribulose bisphosphate carboxylase (EC 4.1.1.39) from Thiobacillus A2 has been purified to homogeneity on the basis of polyacrylamide gel electrophoresis and U.V. analysis during sedimentation velocity studies. The enzyme had an optimum pH of about 8.2 with Tris-HCl buffers. The molecular weight was about 521000 with an Srel. of 16.9. Km for RuBP was 122 muM, for total \"CO2\" it was 4.17 mM, and for Mg2+ 20.0 muM. The absolute requirement for a divalent cation was satisfied by Mg2+ which was replaceable to a certain extent by Mn2+. Activity was not significantly affected by SO(2-4), SO(2-3), or S(2)O(2-3) at 1.0 mM. At this concentration S(2-) caused a 27% stimulation. All mercurials tested were inhibitory. pHMB was the most potent causing about 60% inhibition at 0.04 mM. This inhibition was reversible by low concentrations of cysteine. Cyanide was also inhibitory. Its mode of inhibition with respect to RuBP was un-competitive and with a Ki of 20 muM. Lost activity could be restored partially by GSH or Cu2+. Although azide at the concentration tested had no significant effect on enzyme activity, 2, 4-dinitrophenol at 1.0 mM caused 91% inhibition. Finally, activity was also affected by energy charge.", "contents": "Ribulose biophosphate carboxylase from Thiobacillus A2. Its purification and properties. Ribulose bisphosphate carboxylase (EC 4.1.1.39) from Thiobacillus A2 has been purified to homogeneity on the basis of polyacrylamide gel electrophoresis and U.V. analysis during sedimentation velocity studies. The enzyme had an optimum pH of about 8.2 with Tris-HCl buffers. The molecular weight was about 521000 with an Srel. of 16.9. Km for RuBP was 122 muM, for total \"CO2\" it was 4.17 mM, and for Mg2+ 20.0 muM. The absolute requirement for a divalent cation was satisfied by Mg2+ which was replaceable to a certain extent by Mn2+. Activity was not significantly affected by SO(2-4), SO(2-3), or S(2)O(2-3) at 1.0 mM. At this concentration S(2-) caused a 27% stimulation. All mercurials tested were inhibitory. pHMB was the most potent causing about 60% inhibition at 0.04 mM. This inhibition was reversible by low concentrations of cysteine. Cyanide was also inhibitory. Its mode of inhibition with respect to RuBP was un-competitive and with a Ki of 20 muM. Lost activity could be restored partially by GSH or Cu2+. Although azide at the concentration tested had no significant effect on enzyme activity, 2, 4-dinitrophenol at 1.0 mM caused 91% inhibition. Finally, activity was also affected by energy charge."}
{"id": "PMID:5984", "title": "[Activity and properties of alkaline phosphatase in the plasma and various organs (kidney, liver, small intestine mucosa, bone) of the swine].", "content": "There was a high activity of alkaline phosphatase in the blood plasma of piglets during the first few days of live; enzyme obtained at this time had high heat stability and was readily inhibited by L-phenylalanine (5 mM). The enzyme in blood was inhibited to a greater extent than alkaline phosphatase from intestinal mucosa. With increasing age there was a fall in heat stability and in the ease with that the enzyme could be inhibited by phenylalanine. The proportion of alkaline phosphatase derived from bone and present in blood plasma increased with increasing age. Two isoenzymes were detected in liver, kidney, lung, intestinal mucosa and endometrial mucosa by electrophoresis in polyacrylamide gel. Heat lability and inhibition by phenylalanine were good criteria for differentiating different types of alkaline phosphatase in pigs. In the case of alkaline phosphatase in blood plasma, disodium phenylphosphate was split more readily than p-nitrophenyl phosphate and very much more readily than phenolphthalein diphosphate and beta-glycerophosphate.", "contents": "[Activity and properties of alkaline phosphatase in the plasma and various organs (kidney, liver, small intestine mucosa, bone) of the swine]. There was a high activity of alkaline phosphatase in the blood plasma of piglets during the first few days of live; enzyme obtained at this time had high heat stability and was readily inhibited by L-phenylalanine (5 mM). The enzyme in blood was inhibited to a greater extent than alkaline phosphatase from intestinal mucosa. With increasing age there was a fall in heat stability and in the ease with that the enzyme could be inhibited by phenylalanine. The proportion of alkaline phosphatase derived from bone and present in blood plasma increased with increasing age. Two isoenzymes were detected in liver, kidney, lung, intestinal mucosa and endometrial mucosa by electrophoresis in polyacrylamide gel. Heat lability and inhibition by phenylalanine were good criteria for differentiating different types of alkaline phosphatase in pigs. In the case of alkaline phosphatase in blood plasma, disodium phenylphosphate was split more readily than p-nitrophenyl phosphate and very much more readily than phenolphthalein diphosphate and beta-glycerophosphate."}
{"id": "PMID:5985", "title": "Glycogenolysis in the heart and skeletal muscle during stimulation and blocking of cholinergic receptors. III. Action of acetylcholine under conditions of sympathicolysis.", "content": "Changes in enzymatic activities in phosphorolytic and hydrolytic glycogenolysis in the working heart and in resting skeletal muscle after intravenous injection of sympathicolytic compounds were studied in vitro. Reserpine, alderline and ligation of the adrenals inhibited the influence of acetylcholine on phosphorylase, Reserpine alone or ligation of the adrenals caused an increase in hydrolytic activity similar to that produced by compounds acting on the ganglia. This confirms the concept according to which the adrenergic system (beta-receptor) inhibits hydrolytic activity during glycogenolysis.", "contents": "Glycogenolysis in the heart and skeletal muscle during stimulation and blocking of cholinergic receptors. III. Action of acetylcholine under conditions of sympathicolysis. Changes in enzymatic activities in phosphorolytic and hydrolytic glycogenolysis in the working heart and in resting skeletal muscle after intravenous injection of sympathicolytic compounds were studied in vitro. Reserpine, alderline and ligation of the adrenals inhibited the influence of acetylcholine on phosphorylase, Reserpine alone or ligation of the adrenals caused an increase in hydrolytic activity similar to that produced by compounds acting on the ganglia. This confirms the concept according to which the adrenergic system (beta-receptor) inhibits hydrolytic activity during glycogenolysis."}
{"id": "PMID:5989", "title": "[Morphologic (bioptic) conferences: experience with organization, tasks and results].", "content": "The article deals with the experience in organization of practical conferences in Moscow (The Central Institute of Advanced Medical Training) and in Lvov. The conferences enable pathoanatomists of various institutions to obtain consultation concerning bioptic material, to exchange view with regard for any individual observation. This new form of a collective considaration of complex biopsies should be regarded as one of important methods of the work of pathoanatomists. Some problems associated with interpretation of bioptic specimens, avoidance of errors in the process of an investigation of histological preparations, as well as with the role of the conferences in the upgrading professional qualities of pathoanatomists are discussed.", "contents": "[Morphologic (bioptic) conferences: experience with organization, tasks and results]. The article deals with the experience in organization of practical conferences in Moscow (The Central Institute of Advanced Medical Training) and in Lvov. The conferences enable pathoanatomists of various institutions to obtain consultation concerning bioptic material, to exchange view with regard for any individual observation. This new form of a collective considaration of complex biopsies should be regarded as one of important methods of the work of pathoanatomists. Some problems associated with interpretation of bioptic specimens, avoidance of errors in the process of an investigation of histological preparations, as well as with the role of the conferences in the upgrading professional qualities of pathoanatomists are discussed."}
{"id": "PMID:5993", "title": "Biomedical aspects of oxygen regulator performance: I. Static characteristics.", "content": "Static performance characteristics of current-inventory USAF oxygen regulators were evaluated with the use of a specialized regulator test stand. Outlet suction pressures, flows, positive pressures, and delivered oxygen dilutions were monitored and recorded as functions of operational altitudes. General findings indicated that: 1) excessive oxygen addition occurs in all models, especially at low cabin altitudes; 2) positive pressure schedules generally conform to specifications; 3) negative suction pressures for most regulators are less than -2.54 cm H2O. The validity of static evaluation is discussed and data interpretation is considered with respect to biomedical compatibility emphasizing maintenance of crewmember physiological sufficiency.", "contents": "Biomedical aspects of oxygen regulator performance: I. Static characteristics. Static performance characteristics of current-inventory USAF oxygen regulators were evaluated with the use of a specialized regulator test stand. Outlet suction pressures, flows, positive pressures, and delivered oxygen dilutions were monitored and recorded as functions of operational altitudes. General findings indicated that: 1) excessive oxygen addition occurs in all models, especially at low cabin altitudes; 2) positive pressure schedules generally conform to specifications; 3) negative suction pressures for most regulators are less than -2.54 cm H2O. The validity of static evaluation is discussed and data interpretation is considered with respect to biomedical compatibility emphasizing maintenance of crewmember physiological sufficiency."}
{"id": "PMID:5994", "title": "Biomedical aspects of oxygen regulator performance: II. dynamic characteristics.", "content": "Several oxygen regulators were quantitatively assessed during interface with dynamic respiratory simulation and human user breathing. Continuous measurements of regulator flow, delivered pressure, and delivered oxygenation was provided during variable tidal volumes and breathing frequencies as accomplished initially with breathing simulation and subsequently with human users. The regulators demonstrated large sensitivity to flow demand and the characteristics of the inspiratory flow pulse. Large variations in outlet suction pressure and delivered oxygen concentration accompanied the variable breathing modes of human subjects. The inability of oxygen regulators to consistently provide required oxygen/air delivery is discussed with respect ot inadequate performance specifications currently used.", "contents": "Biomedical aspects of oxygen regulator performance: II. dynamic characteristics. Several oxygen regulators were quantitatively assessed during interface with dynamic respiratory simulation and human user breathing. Continuous measurements of regulator flow, delivered pressure, and delivered oxygenation was provided during variable tidal volumes and breathing frequencies as accomplished initially with breathing simulation and subsequently with human users. The regulators demonstrated large sensitivity to flow demand and the characteristics of the inspiratory flow pulse. Large variations in outlet suction pressure and delivered oxygen concentration accompanied the variable breathing modes of human subjects. The inability of oxygen regulators to consistently provide required oxygen/air delivery is discussed with respect ot inadequate performance specifications currently used."}
{"id": "PMID:5995", "title": "Short-chain fatty acid synthesis in brain. Subcellular localization and changes during development.", "content": "Acetyl-CoA synthase (EC 6.2.1.1), Propionyl-CoA synthase (EC 6.2.1.-) and butyryl-CoA synthase (EC 6.2.1.2) were measured in subcellular fractions prepared by primary and density-gradient fractionation from adult rat brain by a method resulting in recoveries close to 100%. Most of the activity of the three enzymes was recovered in the crude mitochondrial fraction. On subfractionation of this crude mitochondrial fraction with continuous sucrose density gradients, most of the activity of the three enzymes was found at a higher density than NAD+-isocitrate dehydrogenase and at about the same density as glutamate dehydrogenase, confirming earlier reported data for acetyl-CoA synthase. The finding that propionyl-CoA synthase and butyryl-CoA synthase had about the same distribution in the gradients as acetyl-CoA synthase adds support to the hypothesis that mitochondria involved in the metabolism of these short-chain fatty acids (all three of which have been shown to result in a rapid and high labelling of glutamine in vivo) form a distinct subpopulation of the total mitochondrial population. The three synthase activities were found to differ from each other in their rate of change and their subcellular localization during rat brain development. This, in combination with the observation that in gradients of adult brain preparations the three activities did not completely overlap, suggests that the three synthase activities are not present in the same proportion to each other in the same subpopulation (s) of mitochondria in the brain.", "contents": "Short-chain fatty acid synthesis in brain. Subcellular localization and changes during development. Acetyl-CoA synthase (EC 6.2.1.1), Propionyl-CoA synthase (EC 6.2.1.-) and butyryl-CoA synthase (EC 6.2.1.2) were measured in subcellular fractions prepared by primary and density-gradient fractionation from adult rat brain by a method resulting in recoveries close to 100%. Most of the activity of the three enzymes was recovered in the crude mitochondrial fraction. On subfractionation of this crude mitochondrial fraction with continuous sucrose density gradients, most of the activity of the three enzymes was found at a higher density than NAD+-isocitrate dehydrogenase and at about the same density as glutamate dehydrogenase, confirming earlier reported data for acetyl-CoA synthase. The finding that propionyl-CoA synthase and butyryl-CoA synthase had about the same distribution in the gradients as acetyl-CoA synthase adds support to the hypothesis that mitochondria involved in the metabolism of these short-chain fatty acids (all three of which have been shown to result in a rapid and high labelling of glutamine in vivo) form a distinct subpopulation of the total mitochondrial population. The three synthase activities were found to differ from each other in their rate of change and their subcellular localization during rat brain development. This, in combination with the observation that in gradients of adult brain preparations the three activities did not completely overlap, suggests that the three synthase activities are not present in the same proportion to each other in the same subpopulation (s) of mitochondria in the brain."}
{"id": "PMID:5996", "title": "Proton translocation and the respiratory nitrate reductase of Escherichia coli.", "content": "Stoicheometries and rates of proton translocation associated with respiratory reduction of NO3- have been measured for spheroplasts of Escherichia coli grown anaerobically in the presence of NO3-. Observed stoicheiometries [leads to H+/NO3- ratio; P. Mitchell (1966) Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation, Glynn Research, Bodmin] were approx. 4 for L-malate oxidation and approx. 2 for succinate, D-lactate and glycerol oxidation. Measurements of the leads to H+/2e- ratio with formate as the reductant and oxygen or NO3- as the oxidant were complicated by pH changes associated with formate uptake and CO2 formation. Nevertheless, it was possible to conclude that the site of formate oxidation is on the inner aspect of the cytoplasmic membrane, that the leads to H+/O ratio for formate oxidation is approx. 4, and that the leads to H+/NO3- ratio is greater than 2. Measurements of the rate of NO3- penetration into osmotically sensitive spheroplasts demonstrated an electrogenic entry of NO3- anion. The permeability coefficient for nitrate entry at 30 degrees C was between 10(-9) and 10(-10) cm- s(-1). The calculated rate of nitrate entry at the concentration typically used for the assay of nitrate reductase (EC 1.7.99.4) activity was about 0.1% of that required to support the observed rate of nitrate reduction by reduced Benzyl Viologen. Measurements of the distribution of nitrate between the intracellular and extracellular spaces of a haem-less mutant, de-repressed for nitrate reductase but unable to reduce nitrate by the respiratory chain, showed that, irrespective of the presence or the absence of added glucose, nitrate was not concentrated intracellularly. Osmotic-swelling experiments showed that the rate of diffusion of azid anion across the cytoplasmic membrane is relatively low in comparison with the fast diffusion of hydrazoic acid. The inhibitory effect of azide on nitrate reductase was not altered by treatments that modify pH gradients across the cytoplasmic membrane. It is concluded that the nitrate-reducing azide-sensitive site of nitrate reductase is located on the outer aspect of the cytoplasmic membrane. The consequences of this location for mechanisms of proton translocation driven by nitrate reduction are discussed, and lead to the proposal that the nitrate reductase of the cytoplasmic membrane is vectorial, reducing nitrate on the outer aspect of the membrane with 2H+ and 2e- that have crossed from the inner aspect of the membrane.", "contents": "Proton translocation and the respiratory nitrate reductase of Escherichia coli. Stoicheometries and rates of proton translocation associated with respiratory reduction of NO3- have been measured for spheroplasts of Escherichia coli grown anaerobically in the presence of NO3-. Observed stoicheiometries [leads to H+/NO3- ratio; P. Mitchell (1966) Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation, Glynn Research, Bodmin] were approx. 4 for L-malate oxidation and approx. 2 for succinate, D-lactate and glycerol oxidation. Measurements of the leads to H+/2e- ratio with formate as the reductant and oxygen or NO3- as the oxidant were complicated by pH changes associated with formate uptake and CO2 formation. Nevertheless, it was possible to conclude that the site of formate oxidation is on the inner aspect of the cytoplasmic membrane, that the leads to H+/O ratio for formate oxidation is approx. 4, and that the leads to H+/NO3- ratio is greater than 2. Measurements of the rate of NO3- penetration into osmotically sensitive spheroplasts demonstrated an electrogenic entry of NO3- anion. The permeability coefficient for nitrate entry at 30 degrees C was between 10(-9) and 10(-10) cm- s(-1). The calculated rate of nitrate entry at the concentration typically used for the assay of nitrate reductase (EC 1.7.99.4) activity was about 0.1% of that required to support the observed rate of nitrate reduction by reduced Benzyl Viologen. Measurements of the distribution of nitrate between the intracellular and extracellular spaces of a haem-less mutant, de-repressed for nitrate reductase but unable to reduce nitrate by the respiratory chain, showed that, irrespective of the presence or the absence of added glucose, nitrate was not concentrated intracellularly. Osmotic-swelling experiments showed that the rate of diffusion of azid anion across the cytoplasmic membrane is relatively low in comparison with the fast diffusion of hydrazoic acid. The inhibitory effect of azide on nitrate reductase was not altered by treatments that modify pH gradients across the cytoplasmic membrane. It is concluded that the nitrate-reducing azide-sensitive site of nitrate reductase is located on the outer aspect of the cytoplasmic membrane. The consequences of this location for mechanisms of proton translocation driven by nitrate reduction are discussed, and lead to the proposal that the nitrate reductase of the cytoplasmic membrane is vectorial, reducing nitrate on the outer aspect of the membrane with 2H+ and 2e- that have crossed from the inner aspect of the membrane."}
{"id": "PMID:5997", "title": "Subcellular structure of bovine thyroid gland. A study on bovine thyroid membranes by buoyant-density-gradient centrifugation in a B-XIV zonal rotor.", "content": "A combined mitochondrial and light mitochondrial fraction and a microsomal fraction were isolated from bovine thyroid gland and fractionated further in a B-XIV zonal rotor. A density gradient ranging from 20 to 50% (w/w) sucrose was used. The rotor was operated for 3 h at 45 000 rev./min. All manipulations were performed at 4 degrees C and at pH 7.4. 2. Membranous material was recovered in two zones: zone I, containing microsomal material derived from both smooth endoplasmic reticulum and plasma membranes and probably also from other smooth membranes; zone II, containing material from rough endoplasmic reticulum. 3. Increasing the pH of the medium up to 8.6, or the addition of Mg2+ to the medium resulted in the formation of a single zone at intermediate densities (aggregation of membranes?). An analogous effect was obtained after treatment with Pb (NO3) 2. 4. In the presence of heparin (50 i.u./ml) the bulk of the membranes was found in zone I. This was due to the release of ribosomes from the rough endoplasmic reticulum.", "contents": "Subcellular structure of bovine thyroid gland. A study on bovine thyroid membranes by buoyant-density-gradient centrifugation in a B-XIV zonal rotor. A combined mitochondrial and light mitochondrial fraction and a microsomal fraction were isolated from bovine thyroid gland and fractionated further in a B-XIV zonal rotor. A density gradient ranging from 20 to 50% (w/w) sucrose was used. The rotor was operated for 3 h at 45 000 rev./min. All manipulations were performed at 4 degrees C and at pH 7.4. 2. Membranous material was recovered in two zones: zone I, containing microsomal material derived from both smooth endoplasmic reticulum and plasma membranes and probably also from other smooth membranes; zone II, containing material from rough endoplasmic reticulum. 3. Increasing the pH of the medium up to 8.6, or the addition of Mg2+ to the medium resulted in the formation of a single zone at intermediate densities (aggregation of membranes?). An analogous effect was obtained after treatment with Pb (NO3) 2. 4. In the presence of heparin (50 i.u./ml) the bulk of the membranes was found in zone I. This was due to the release of ribosomes from the rough endoplasmic reticulum."}
{"id": "PMID:5998", "title": "Characterization of the terminal stages of chlorophyll (ide) synthesis in etioplast membrane preparations.", "content": "1. Chlorophyll (ide) formation from protochlorophyll (ide) that is normally inactive was demonstrated in etioplast membranes isolated from maize and barlley plants, the process being dependent on intermittent illumination and the addition of NADPH. 2. The addition of NADPH to the membranes was shown to result in the conversion of inactive protochlorophyll (ide) absorbing at about 630 nm into a form(s) with light-absorption maxima at about 640 and 652 nm, both of which disappear when chlorophyll (ide) is formed on illumination. 3. The temperature-dependence of the activation process and its response to a variety of reagents were examined. From these, the conclusion is drawn that -SH groups are involved in the activation but in the active complex these are unavailable for reaction with -SH reagents. 4. Evidence is presented for the occurrence of glucose 6-phosphate dehydrogenase activity within etioplasts and the suggestion is made that the oxidative pentose phosphate pathway can provide the NADPH required for chlorophyll biosynthesis during the early stages of greening.", "contents": "Characterization of the terminal stages of chlorophyll (ide) synthesis in etioplast membrane preparations. 1. Chlorophyll (ide) formation from protochlorophyll (ide) that is normally inactive was demonstrated in etioplast membranes isolated from maize and barlley plants, the process being dependent on intermittent illumination and the addition of NADPH. 2. The addition of NADPH to the membranes was shown to result in the conversion of inactive protochlorophyll (ide) absorbing at about 630 nm into a form(s) with light-absorption maxima at about 640 and 652 nm, both of which disappear when chlorophyll (ide) is formed on illumination. 3. The temperature-dependence of the activation process and its response to a variety of reagents were examined. From these, the conclusion is drawn that -SH groups are involved in the activation but in the active complex these are unavailable for reaction with -SH reagents. 4. Evidence is presented for the occurrence of glucose 6-phosphate dehydrogenase activity within etioplasts and the suggestion is made that the oxidative pentose phosphate pathway can provide the NADPH required for chlorophyll biosynthesis during the early stages of greening."}
{"id": "PMID:5999", "title": "Succinate uptake and related proton movements in Escherichia coli K12.", "content": "1. The apparent Km values for succinate uptake by whole cells of Escherichia coli K12 depend on pH in the range 6.5-7.4.2. Uptake of succinate in lightly buffered medium is accompanied by proton uptake. 3. The apparent Km values for succinate uptake and for succinate-induced proton uptake are similar. 4. Approximately two protons enter the cell with each succinate molecule. 5. The pattern of inhibition of succinate uptake is similar to that of succinate-induced proton uptake. 6. Uptake of fumarate and malate, which share the succinate-transport system, is also accompanied by the uptake of approximately two protons per molecule of fumarate or malate. 7. Uptake of aspartate by the dicarboxylic acid-transport system is accompanied by the uptake of approximatley two protons per molecule of asparatate. 8. It is concluded that uptake of dicarboxylic acids by the dicarboxylic acid-transport system is obligatorily coupled to proton uptake such that succinate, malate and fumarate are taken up in electroneutral form and asparate is taken up in cationic form. 9. These results are consistent with, though they do not definitely prove, the energization of succinate uptake of the deltapH.", "contents": "Succinate uptake and related proton movements in Escherichia coli K12. 1. The apparent Km values for succinate uptake by whole cells of Escherichia coli K12 depend on pH in the range 6.5-7.4.2. Uptake of succinate in lightly buffered medium is accompanied by proton uptake. 3. The apparent Km values for succinate uptake and for succinate-induced proton uptake are similar. 4. Approximately two protons enter the cell with each succinate molecule. 5. The pattern of inhibition of succinate uptake is similar to that of succinate-induced proton uptake. 6. Uptake of fumarate and malate, which share the succinate-transport system, is also accompanied by the uptake of approximately two protons per molecule of fumarate or malate. 7. Uptake of aspartate by the dicarboxylic acid-transport system is accompanied by the uptake of approximatley two protons per molecule of asparatate. 8. It is concluded that uptake of dicarboxylic acids by the dicarboxylic acid-transport system is obligatorily coupled to proton uptake such that succinate, malate and fumarate are taken up in electroneutral form and asparate is taken up in cationic form. 9. These results are consistent with, though they do not definitely prove, the energization of succinate uptake of the deltapH."}
{"id": "PMID:6000", "title": "Evidence against the participation of the gamma-glutamyltransferase-gamma-glutamylcylclotransferase pathway in amino acid transport by rabbit erythrocytes.", "content": "The GSH concentration of rabbit erythrocytes was monitored under conditions of large net transport of alanine, phenylalane and lysine in the absence of glucose. In no case was there an appreciable alteration in GSH concentration during amino acid uptake. It is suggested that the gamma-glutamyltransferase-gamma-glutamylcyclotransferase pathway does not participate in amino acid transport by these cells.", "contents": "Evidence against the participation of the gamma-glutamyltransferase-gamma-glutamylcylclotransferase pathway in amino acid transport by rabbit erythrocytes. The GSH concentration of rabbit erythrocytes was monitored under conditions of large net transport of alanine, phenylalane and lysine in the absence of glucose. In no case was there an appreciable alteration in GSH concentration during amino acid uptake. It is suggested that the gamma-glutamyltransferase-gamma-glutamylcyclotransferase pathway does not participate in amino acid transport by these cells."}
{"id": "PMID:6001", "title": "An investigation of protein conformation of cytochrome c by using cytochrome c insolubilized on to agarose gel.", "content": "Cytochrome c insolubilized on to agarose gel was shown to be more resistant to denaturation and carboxymethylation than the soluble protein. These differences are discussed both with respect to the conformational changes that take place during denaturation of cytochrome c and with respect to the pH-dependent forms of carboxymethyl-cytochrome c.", "contents": "An investigation of protein conformation of cytochrome c by using cytochrome c insolubilized on to agarose gel. Cytochrome c insolubilized on to agarose gel was shown to be more resistant to denaturation and carboxymethylation than the soluble protein. These differences are discussed both with respect to the conformational changes that take place during denaturation of cytochrome c and with respect to the pH-dependent forms of carboxymethyl-cytochrome c."}
{"id": "PMID:6002", "title": "Factors affecting the activity of citrate synthase of Acetobacter xylinum and its possible regulatory role.", "content": "The citrate synthase activity of Acetobacter xylinum cells grown on glucose was the same as of cells grown on intermediates of the tricarboxylic acid cycle. The activity of citrate synthase in extracts is compatible with the overall rate of acetate oxidation in vivo. The enzyme was purified 47-fold from sonic extracts and its molecular weight was determined to be 280000 by gel filtration. It has an optimum activity at pH 8.4. Reaction rates with the purified enzyme were hyperbolic functions of both acetyl-CoA and oxaloacetate. The Km for acetyl-CoA is 18 mum and that for oxaloacetate 8.7 mum. The enzyme is inhibited by ATP according to classical kinetic patterns. This inhibition is competitive with respect to acetyl-CoA (Ki = 0.9 mM) and non-competitive with respect to oxaloacetate. It is not affected by changes in pH and ionic strength and is not relieved by an excess of Mg2+ ions. Unlike other Gram-negative bacteria, the A. xylinum enzyme is not inhibited by NADH, but is inhibited by high concentrations of NADPH. The activity of the enzyme varies with energy charge in a manner consistent with its role in energy metabolism. It is suggested that the flux through the tricarboxylic acid cycle in A. xylinum is regulated by modulation of citrate synthase activity in response to the energy state of the cells.", "contents": "Factors affecting the activity of citrate synthase of Acetobacter xylinum and its possible regulatory role. The citrate synthase activity of Acetobacter xylinum cells grown on glucose was the same as of cells grown on intermediates of the tricarboxylic acid cycle. The activity of citrate synthase in extracts is compatible with the overall rate of acetate oxidation in vivo. The enzyme was purified 47-fold from sonic extracts and its molecular weight was determined to be 280000 by gel filtration. It has an optimum activity at pH 8.4. Reaction rates with the purified enzyme were hyperbolic functions of both acetyl-CoA and oxaloacetate. The Km for acetyl-CoA is 18 mum and that for oxaloacetate 8.7 mum. The enzyme is inhibited by ATP according to classical kinetic patterns. This inhibition is competitive with respect to acetyl-CoA (Ki = 0.9 mM) and non-competitive with respect to oxaloacetate. It is not affected by changes in pH and ionic strength and is not relieved by an excess of Mg2+ ions. Unlike other Gram-negative bacteria, the A. xylinum enzyme is not inhibited by NADH, but is inhibited by high concentrations of NADPH. The activity of the enzyme varies with energy charge in a manner consistent with its role in energy metabolism. It is suggested that the flux through the tricarboxylic acid cycle in A. xylinum is regulated by modulation of citrate synthase activity in response to the energy state of the cells."}
{"id": "PMID:6003", "title": "Bovine spleen cathepsin B1 and collagenolytic cathepsin. A comparative study of the properties of the two enzymes in the degradation of native collagen.", "content": "Bovine spleen cathepsin B1 and collagenolytic cathepsin were separated by chromatography on Amberlite IRC-50 and collagenolytic cathepsin was partially purified by chromatography on DEAE-Sephadex (A-50). 2. Collagenolytic cathepsin degraded insoluble tendon collagen maximally at pH 3.5 and 28 degrees C; mainly alpha-chain components were released into solution. At 28 degrees C the telopeptides in soluble skin collagen were also cleaved to yield alpha-chain components. Collagenolytic cathepsin was thus similar to cathepsin B1 in its action against native collagen, but mixtures of these two enzymes exhibited a synergistic effect. 3. The addition of thiol-blocking compounds produced similar inhibition of collagenolytic cathepsin and cathepsin B1. The enzyme responded similarly to all other compounds tested except to 6-aminohexanoic acid, when collagenolytic cathepsin was slightly activated and cathepsin B1 was almost unaffected. 4. Leupeptin, which is a structural analogue of arginine-containing synthetic substrates, inhibited collagenolytic cathepsin as effectively as cathepsin B1. Collagenolytic cathepsin was shown to retain a low residual activity against alpha-N-benzoyl-DL-arginine p-nitroanilide during purification which was equivalent to 0.2% of the activity of cathepsin B1. 5. Cathepsin B1 and collagenolytic cathepsin could not be separated by affinity chromatography on organomercurial-Sepharose 4B. The two enzymes could be resolved on DEAE-Sephadex (A-50) and by isoelectric focusing in an Ampholine pH gradient. The pI of the major cathepsin B1 isoenzyme was 4.9 and the pI of collagenolytic cathepsin was 6.4. 6. From chromatography on Sephadex G-75 (superfine grade) the molecular weights were calculated to be 26000 for cathepsin B1 and 20000 for collagenolytic cathepsin. The difference in molecular weight was confirmed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis.", "contents": "Bovine spleen cathepsin B1 and collagenolytic cathepsin. A comparative study of the properties of the two enzymes in the degradation of native collagen. Bovine spleen cathepsin B1 and collagenolytic cathepsin were separated by chromatography on Amberlite IRC-50 and collagenolytic cathepsin was partially purified by chromatography on DEAE-Sephadex (A-50). 2. Collagenolytic cathepsin degraded insoluble tendon collagen maximally at pH 3.5 and 28 degrees C; mainly alpha-chain components were released into solution. At 28 degrees C the telopeptides in soluble skin collagen were also cleaved to yield alpha-chain components. Collagenolytic cathepsin was thus similar to cathepsin B1 in its action against native collagen, but mixtures of these two enzymes exhibited a synergistic effect. 3. The addition of thiol-blocking compounds produced similar inhibition of collagenolytic cathepsin and cathepsin B1. The enzyme responded similarly to all other compounds tested except to 6-aminohexanoic acid, when collagenolytic cathepsin was slightly activated and cathepsin B1 was almost unaffected. 4. Leupeptin, which is a structural analogue of arginine-containing synthetic substrates, inhibited collagenolytic cathepsin as effectively as cathepsin B1. Collagenolytic cathepsin was shown to retain a low residual activity against alpha-N-benzoyl-DL-arginine p-nitroanilide during purification which was equivalent to 0.2% of the activity of cathepsin B1. 5. Cathepsin B1 and collagenolytic cathepsin could not be separated by affinity chromatography on organomercurial-Sepharose 4B. The two enzymes could be resolved on DEAE-Sephadex (A-50) and by isoelectric focusing in an Ampholine pH gradient. The pI of the major cathepsin B1 isoenzyme was 4.9 and the pI of collagenolytic cathepsin was 6.4. 6. From chromatography on Sephadex G-75 (superfine grade) the molecular weights were calculated to be 26000 for cathepsin B1 and 20000 for collagenolytic cathepsin. The difference in molecular weight was confirmed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis."}
{"id": "PMID:6004", "title": "Gamma-glutamyltransferase of rat kidney. Simultaneous assay of the hydrolysis and transfer reactions with (glutamate-14C)glutathione.", "content": "1. The hydrolytic and transfer reactions catalysed by rat kidney-gamma-glutamyltransferase (EC 2.3.2.2) were studied in vitro with substrates [U-14C]glutamic acid-labelled glutathione and methionine. Initial-velocity patterns, isotope-exchange and binding studies were consistent with a branched non-sequential mechanism in which a gamma-glutamyl-enzyme intermediate may react either with water (hydrolysis) or with methionine (gamma-glutamyl transfer). 2. The Michaelis constant for glutathione in hydrolysis was 13.9 +/- 1.4 mum, for glutathione in transfer it was 113 +/- 15 muM and for methionine as substrate it was 4.7 +/- 0.7 mM. At substrate concentrations in the ranges of their respective Michaelis constants, the rate of transfer was about ten times higher than that of hydrolysis, but at concentrations of methionine approximating to the physiological (64 muM in rat plasma) the transfer is negligible. 3. The enzyme is reported to lie on the luminal surface of the proximal straight kidney tubule. In this situation, if the kinetic results obtained with the detergent-solubilized enzyme are relevant to the behavior of the enzyme in vivo, it appears likely that the main function of renal gamma-glutamyltransferase is not in amino acid transport, but rather to hydrolyse glutathione in the renal filtrate.", "contents": "Gamma-glutamyltransferase of rat kidney. Simultaneous assay of the hydrolysis and transfer reactions with (glutamate-14C)glutathione. 1. The hydrolytic and transfer reactions catalysed by rat kidney-gamma-glutamyltransferase (EC 2.3.2.2) were studied in vitro with substrates [U-14C]glutamic acid-labelled glutathione and methionine. Initial-velocity patterns, isotope-exchange and binding studies were consistent with a branched non-sequential mechanism in which a gamma-glutamyl-enzyme intermediate may react either with water (hydrolysis) or with methionine (gamma-glutamyl transfer). 2. The Michaelis constant for glutathione in hydrolysis was 13.9 +/- 1.4 mum, for glutathione in transfer it was 113 +/- 15 muM and for methionine as substrate it was 4.7 +/- 0.7 mM. At substrate concentrations in the ranges of their respective Michaelis constants, the rate of transfer was about ten times higher than that of hydrolysis, but at concentrations of methionine approximating to the physiological (64 muM in rat plasma) the transfer is negligible. 3. The enzyme is reported to lie on the luminal surface of the proximal straight kidney tubule. In this situation, if the kinetic results obtained with the detergent-solubilized enzyme are relevant to the behavior of the enzyme in vivo, it appears likely that the main function of renal gamma-glutamyltransferase is not in amino acid transport, but rather to hydrolyse glutathione in the renal filtrate."}
{"id": "PMID:6005", "title": "Equilibrium and kinetic studies of the aggregation of porphyrins in aqueous solution.", "content": "An investigation of the behavior of protoporphyrin IX, deuteroporphyrin IX, haematoporphyrin IX and coproporphyrin III in aqueous solution revealed extensive and complex aggregation processes. Protoporphyrin appears to be highly aggregated under all conditions studied. At concentrations below 4 muM, aggregation of deutero-, haemato- and coproporphyrin is probably restricted to dimerization. At approx. 4muM each of these three porphyrins exhibits sharp changes in spectra consistent with a \"micellization\" process to form large aggregates of unknown size. This critical concentration increases with increasing temperature and pH, but is not very sensitive to variation in ionic strength. Temperature-jump kinetic studies on deuteroporphyrin also imply an initial dimerization process, the rate constants for which are comparable with those for various synthetic porphyrins, followed by a further extensive aggragation. The ability of a particular porphyrin to dimerize appears to parallel that of the corresponding iron(III) complexes (ferrihaems), although it is thought that ferrihaems do not exhibit further aggregation under these conditions.", "contents": "Equilibrium and kinetic studies of the aggregation of porphyrins in aqueous solution. An investigation of the behavior of protoporphyrin IX, deuteroporphyrin IX, haematoporphyrin IX and coproporphyrin III in aqueous solution revealed extensive and complex aggregation processes. Protoporphyrin appears to be highly aggregated under all conditions studied. At concentrations below 4 muM, aggregation of deutero-, haemato- and coproporphyrin is probably restricted to dimerization. At approx. 4muM each of these three porphyrins exhibits sharp changes in spectra consistent with a \"micellization\" process to form large aggregates of unknown size. This critical concentration increases with increasing temperature and pH, but is not very sensitive to variation in ionic strength. Temperature-jump kinetic studies on deuteroporphyrin also imply an initial dimerization process, the rate constants for which are comparable with those for various synthetic porphyrins, followed by a further extensive aggragation. The ability of a particular porphyrin to dimerize appears to parallel that of the corresponding iron(III) complexes (ferrihaems), although it is thought that ferrihaems do not exhibit further aggregation under these conditions."}
{"id": "PMID:6006", "title": "Kinetic studies on glucoamylase of rabbit small intestine.", "content": "The kinetic properties of a maltase-glucoamylase complex with a neutral pH optimum, purified to homogeneity from the brush borders of the rabbit small intestine, are described. It has a broad range of substrate specificity, hydrolysing di- and poly-saccharides with alpha-1,4 and alpha-1,6 linkages. The Km and Vmax, values of the enzyme for the various substrates were determined. Starch and maltose were its best substrates. The kinetics of hydrolysis of two synthetic linear maltosaccharides, namely maltotriose and maltopentaose, were studied. Mixed-substrate incubation studies revealed the presence of at least two interacting sites on the enzyme, and the data were further analysed by the use of a number of non-substrate inhibitors.", "contents": "Kinetic studies on glucoamylase of rabbit small intestine. The kinetic properties of a maltase-glucoamylase complex with a neutral pH optimum, purified to homogeneity from the brush borders of the rabbit small intestine, are described. It has a broad range of substrate specificity, hydrolysing di- and poly-saccharides with alpha-1,4 and alpha-1,6 linkages. The Km and Vmax, values of the enzyme for the various substrates were determined. Starch and maltose were its best substrates. The kinetics of hydrolysis of two synthetic linear maltosaccharides, namely maltotriose and maltopentaose, were studied. Mixed-substrate incubation studies revealed the presence of at least two interacting sites on the enzyme, and the data were further analysed by the use of a number of non-substrate inhibitors."}
{"id": "PMID:6007", "title": "Bile acids of snakes of the subfamily Viperinae and the biosynthesis of C-23-hydroxylated bile acids in liver homogenate fractions from the adder, Vipera berus (Linn.).", "content": "1. Analysis of bile salts of four snakes of the subfamily Viperinae showed that their bile acids consisted mainly of C-23-hydroxylated bile acids. 2. Incubations of 14C-labelled sodium cholate (3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oate) and deoxycholate (3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oate) with whole and fractionated adder liver homogenates were carried out in the presence of molecular oxygen and NADPH or an NADPH-generating system. The formation of C-23-hydroxylated bile acids, namely bitocholic acid (3 alpha, 12 alpha, 23xi-trihydroxy-5 beta-cholan-24-oic acid) and 3 alpha, 7 alpha, 12 alpha, 23 xi-tetrahydroxy-cholanic acid (3 alpha, 7 alpha, 12 alpha, 23 xi-tetrahydroxy-5 beta-cholan-24-oic acid), was observed mainly in the microsomal fraction and partly in the mitochondrial fraction. 3. Biosynthetic pathways of C-23-hydroxylated bile acids are discussed.", "contents": "Bile acids of snakes of the subfamily Viperinae and the biosynthesis of C-23-hydroxylated bile acids in liver homogenate fractions from the adder, Vipera berus (Linn.). 1. Analysis of bile salts of four snakes of the subfamily Viperinae showed that their bile acids consisted mainly of C-23-hydroxylated bile acids. 2. Incubations of 14C-labelled sodium cholate (3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oate) and deoxycholate (3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oate) with whole and fractionated adder liver homogenates were carried out in the presence of molecular oxygen and NADPH or an NADPH-generating system. The formation of C-23-hydroxylated bile acids, namely bitocholic acid (3 alpha, 12 alpha, 23xi-trihydroxy-5 beta-cholan-24-oic acid) and 3 alpha, 7 alpha, 12 alpha, 23 xi-tetrahydroxy-cholanic acid (3 alpha, 7 alpha, 12 alpha, 23 xi-tetrahydroxy-5 beta-cholan-24-oic acid), was observed mainly in the microsomal fraction and partly in the mitochondrial fraction. 3. Biosynthetic pathways of C-23-hydroxylated bile acids are discussed."}
{"id": "PMID:6008", "title": "Isolation and some molecular parameters of elastase-like normal proteinases from horse blood leucocytes.", "content": "Cytoplasmic granules were isolated from horse blood polymorphonuclear leucocytes by the heparin method and extracted with 0.9% NaCl by repeated freezing. Soluble proteins were separated on a column of Sephadex G-75 followed by chromatography on a column of CM-Sephadex with a NaCl gradient. Gel filtration, density-gradient centrifugation, isoelectric focusing and 0.1% sodium dodecyl sulphate/polyacrylamide-gel electrophoresis at pH 7.0 and at pH 4.5 were used to determine molecular parameters of proteinases. Three enzymes hydrolysing both casein and N-benzyloxycarbonyl-L-alanine nitrophenyl ester were found in the granule extract: proteinase 1, mol.wt. 38000, pI5.3; proteinase 2A, mol.wt. 24500, pI8.8; and proteinase 2B, mol.wt. 20500, pI above 10. The latter two elastase-like proteinases were purified to apparent homogeneity.", "contents": "Isolation and some molecular parameters of elastase-like normal proteinases from horse blood leucocytes. Cytoplasmic granules were isolated from horse blood polymorphonuclear leucocytes by the heparin method and extracted with 0.9% NaCl by repeated freezing. Soluble proteins were separated on a column of Sephadex G-75 followed by chromatography on a column of CM-Sephadex with a NaCl gradient. Gel filtration, density-gradient centrifugation, isoelectric focusing and 0.1% sodium dodecyl sulphate/polyacrylamide-gel electrophoresis at pH 7.0 and at pH 4.5 were used to determine molecular parameters of proteinases. Three enzymes hydrolysing both casein and N-benzyloxycarbonyl-L-alanine nitrophenyl ester were found in the granule extract: proteinase 1, mol.wt. 38000, pI5.3; proteinase 2A, mol.wt. 24500, pI8.8; and proteinase 2B, mol.wt. 20500, pI above 10. The latter two elastase-like proteinases were purified to apparent homogeneity."}
{"id": "PMID:6009", "title": "Substrate specificity and modifications of the active centre of elastase-like neutral proteinases from horse blood leucocytes.", "content": "Two proteinases (2A and 2B) purified from the granular fraction of horse blood leucocytes degrade casein (Km values 12.8 and 6mg/ml respectively) with maximum activity at pH 7.4 and in the presence of 2m-urea. Urea-denatured haemoglobin, fibrinogen, albumin and resorcin/fuchsin-stained elastin are digested at a slower rate. The enzymes hydrolyse synthetic substrates of elastase, N-benzyloxycarbonyl-L-alanine 4-nitrophenyl ester (Km 0.114 and 0.178 mM) and N-acetyl-tri-L-alanine methyl ester (Km 5.55 and 0.98 mM), but they do not hydrolyse synthetic substrates of trypsin, chymotrypsin and thrombin. The examined proteinases are completely inhibited by 2 mM-di-isopropyl phosphorfluoridate and show a sensitivity to butyl and octyl isocyanates similar to that of pancreatic elastase. The pH-dependence of their photoinactivation in the presence of Rose Bengal indicates the presence of histidine in the active centre. Proteinase 2A rather insensitive to iodination by IC1 as is pancreatic elastase, whereas proteinase 2B is totally inactivated after incorporation of five iodine atoms per enzyme molecule.", "contents": "Substrate specificity and modifications of the active centre of elastase-like neutral proteinases from horse blood leucocytes. Two proteinases (2A and 2B) purified from the granular fraction of horse blood leucocytes degrade casein (Km values 12.8 and 6mg/ml respectively) with maximum activity at pH 7.4 and in the presence of 2m-urea. Urea-denatured haemoglobin, fibrinogen, albumin and resorcin/fuchsin-stained elastin are digested at a slower rate. The enzymes hydrolyse synthetic substrates of elastase, N-benzyloxycarbonyl-L-alanine 4-nitrophenyl ester (Km 0.114 and 0.178 mM) and N-acetyl-tri-L-alanine methyl ester (Km 5.55 and 0.98 mM), but they do not hydrolyse synthetic substrates of trypsin, chymotrypsin and thrombin. The examined proteinases are completely inhibited by 2 mM-di-isopropyl phosphorfluoridate and show a sensitivity to butyl and octyl isocyanates similar to that of pancreatic elastase. The pH-dependence of their photoinactivation in the presence of Rose Bengal indicates the presence of histidine in the active centre. Proteinase 2A rather insensitive to iodination by IC1 as is pancreatic elastase, whereas proteinase 2B is totally inactivated after incorporation of five iodine atoms per enzyme molecule."}
{"id": "PMID:6010", "title": "Purification and properties of arylsulphatase B of human liver.", "content": "1. A purification scheme for an arylsulphatase B from human liver is described. Specificity of purification was achieved by the use of the affinity chromatography on an agrose-4-hydroxy-2-nitrophenyl sulphate derivative. The scheme provides a rapid and convenient method for preparation of a highly purified enzyme. 2. The purified enzyme was examined by isoelectric focusing electrophoresis on polyacrylamide gel and by ultracentrifugation and was found to be catalytically homogenous, with an apparent molecular weight of 50000 and a specific activity of 93.3 units/mg of protein. 3. The kinetic properties of the purified preparation and the effect of various amino acid group-specific reagents on the catalysis of the enzyme are described. The involvement of histidine residues in the active site of the enzyme is suggested. 4. The purified enzyme lost activity rapidly on freezing. The implication of this observation is discussed in terms of a possible dissociation-reaggregation phenomenon induced by cold treatment.", "contents": "Purification and properties of arylsulphatase B of human liver. 1. A purification scheme for an arylsulphatase B from human liver is described. Specificity of purification was achieved by the use of the affinity chromatography on an agrose-4-hydroxy-2-nitrophenyl sulphate derivative. The scheme provides a rapid and convenient method for preparation of a highly purified enzyme. 2. The purified enzyme was examined by isoelectric focusing electrophoresis on polyacrylamide gel and by ultracentrifugation and was found to be catalytically homogenous, with an apparent molecular weight of 50000 and a specific activity of 93.3 units/mg of protein. 3. The kinetic properties of the purified preparation and the effect of various amino acid group-specific reagents on the catalysis of the enzyme are described. The involvement of histidine residues in the active site of the enzyme is suggested. 4. The purified enzyme lost activity rapidly on freezing. The implication of this observation is discussed in terms of a possible dissociation-reaggregation phenomenon induced by cold treatment."}
{"id": "PMID:6011", "title": "Estimation of the dissociation constants of enzyme-substrate complexes from steady-state measurements. Interpretation of pH-independence of Km.", "content": "If the Michaelis constant of an enzyme-catalysed reaction is independent of pH under conditions where the catalytic constant varies with pH, it is equal to the thermodynamic dissociation constant of the enzyme-substrate complex. This is true for realistic mechanisms in which binding and catalytic steps, are clearly distinguished, as well as for the simpler mechanisms that have been considered previously. It is also true for a mechanism in which a bell-shaped pH profile for the catalytic constant results from a change of rate-limiting step with pH. The relaxation time for ionization of a typical group in unbuffered solutions at 25 degrees C is of the order of 0.1 ms at the longest, and is much shorter in buffered solutions. Thus ionizations in almost all enzyme mechanisms can properly be treated as equilibria, provided that ionization is not accompanied by a slow, compulsory change in conformation.", "contents": "Estimation of the dissociation constants of enzyme-substrate complexes from steady-state measurements. Interpretation of pH-independence of Km. If the Michaelis constant of an enzyme-catalysed reaction is independent of pH under conditions where the catalytic constant varies with pH, it is equal to the thermodynamic dissociation constant of the enzyme-substrate complex. This is true for realistic mechanisms in which binding and catalytic steps, are clearly distinguished, as well as for the simpler mechanisms that have been considered previously. It is also true for a mechanism in which a bell-shaped pH profile for the catalytic constant results from a change of rate-limiting step with pH. The relaxation time for ionization of a typical group in unbuffered solutions at 25 degrees C is of the order of 0.1 ms at the longest, and is much shorter in buffered solutions. Thus ionizations in almost all enzyme mechanisms can properly be treated as equilibria, provided that ionization is not accompanied by a slow, compulsory change in conformation."}
{"id": "PMID:6012", "title": "Purification and some properties of acetyl-coenzyme A carboxylase from rabbit mammary gland.", "content": "1. Acetyl-Coa carboxylase from lactating-rabbit mammary gland was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 2. Use of phosphate buffer throughout the purification gave low recovery of enzyme. Consequently, Tris buffers were used in the extraction and in selected stages of the purification procedure. 3. The purified enzyme had a specific activity of 5.15 +/- 0.3 mumol of bicarbonate incorporated/min per mg of protein (mean +/- S.E.M. of five preparations). This represents a purification of 257 +/- 16-fold and a yield of 4.3 +/- 0.13%. 4. The kinetic parameters of the purified enzyme were similar to those reported for the enzyme from other tissue sources. 5. The enzyme was assayed by a spectrophotometric assay and by a [14C]bicarbonate-fixation assay. Short incubation were used in the radio-chemical assay to avoid substantial loss of [14C]bicarbonate.", "contents": "Purification and some properties of acetyl-coenzyme A carboxylase from rabbit mammary gland. 1. Acetyl-Coa carboxylase from lactating-rabbit mammary gland was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 2. Use of phosphate buffer throughout the purification gave low recovery of enzyme. Consequently, Tris buffers were used in the extraction and in selected stages of the purification procedure. 3. The purified enzyme had a specific activity of 5.15 +/- 0.3 mumol of bicarbonate incorporated/min per mg of protein (mean +/- S.E.M. of five preparations). This represents a purification of 257 +/- 16-fold and a yield of 4.3 +/- 0.13%. 4. The kinetic parameters of the purified enzyme were similar to those reported for the enzyme from other tissue sources. 5. The enzyme was assayed by a spectrophotometric assay and by a [14C]bicarbonate-fixation assay. Short incubation were used in the radio-chemical assay to avoid substantial loss of [14C]bicarbonate."}
{"id": "PMID:6013", "title": "Density-gradient sedimentation in silica sols. Anomalous shifts in the banding densities of polystyrene \"latex\" beads.", "content": "When polystyrene \"latex\" beads are centrifuged to equilibrium in gradients of Nalcoag 1030, Nalcoag 1034A and Ludox 130M, which are commercial formulations of colloidal silica, the beads at densities that may be markedly lower or higher than the bulk density. Addition to the gradient of small amounts of certain polymers restores the banding densities towards the expected value. These findings closely mimic previously observed \"density shifts\" of biological particles. A possible model for this anomalous behavior is discussed.", "contents": "Density-gradient sedimentation in silica sols. Anomalous shifts in the banding densities of polystyrene \"latex\" beads. When polystyrene \"latex\" beads are centrifuged to equilibrium in gradients of Nalcoag 1030, Nalcoag 1034A and Ludox 130M, which are commercial formulations of colloidal silica, the beads at densities that may be markedly lower or higher than the bulk density. Addition to the gradient of small amounts of certain polymers restores the banding densities towards the expected value. These findings closely mimic previously observed \"density shifts\" of biological particles. A possible model for this anomalous behavior is discussed."}
{"id": "PMID:6014", "title": "Some observations on the NADP+-linked oxidation of methylglyoxal catalysed by 2-Oxoaldehyde dehydrogenase.", "content": "In the oxidation of methylglyoxal by 2-oxoaldehyde dehydrogenase, the apparent Km value for NADP+ was about 2.5 times lower than the corresponding Km for NAD+; the apparent Km values for methylglyoxal and for the amine activator L-2-aminopropan-1-ol, with NADP+ as cofactor, were also different from those obtained with NAD+. In the presence of NADP+, the enzyme was not activated by P1, in contrast with the activation of the enzyme when NAD+ was used. The significance of the results is discussed.", "contents": "Some observations on the NADP+-linked oxidation of methylglyoxal catalysed by 2-Oxoaldehyde dehydrogenase. In the oxidation of methylglyoxal by 2-oxoaldehyde dehydrogenase, the apparent Km value for NADP+ was about 2.5 times lower than the corresponding Km for NAD+; the apparent Km values for methylglyoxal and for the amine activator L-2-aminopropan-1-ol, with NADP+ as cofactor, were also different from those obtained with NAD+. In the presence of NADP+, the enzyme was not activated by P1, in contrast with the activation of the enzyme when NAD+ was used. The significance of the results is discussed."}
{"id": "PMID:6015", "title": "Lipid biosynthesis in liver slices of the foetal guinea pig.", "content": "Lipid synthesis as measured by the incorporation of acetate or 3H2O into slices of foetal liver, is much higher than in slices of adult liver and shows a peak at about two-thirds of gestation. At this time the synthesis from glucose was low and reached a peak 10 days later. The changes in the activity of ATP citrate lyase, which mirrored acetate incorporation, and the effect of glucose and pyruvate on acetate corporation into lipid suggests that some of the lipid synthesis occurs via intramitochondrial acetyl-CoA production from acetate. Despite this, lipid synthesis was not inhibited by (-)-hydroxycitrate. The low rate of synthesis from glucose at two-thirds of gestation is ascribed to the low activity of pyruvate carboxylase at this time and a role for a phosphoenolpyruvate carboxykinase in providing oxaloacetate for lipogenesis is proposed. The activity of fatty acid synthetase broadly agreed with the changes in lipid synthesis, whereas the activity of acetyl-CoA carboxylase was barely sufficient to account for the rates of lipid synthesis in vivo. Acetate and short-chain fatty acids are likely to be the major precursors for lipid synthesis in vivo.", "contents": "Lipid biosynthesis in liver slices of the foetal guinea pig. Lipid synthesis as measured by the incorporation of acetate or 3H2O into slices of foetal liver, is much higher than in slices of adult liver and shows a peak at about two-thirds of gestation. At this time the synthesis from glucose was low and reached a peak 10 days later. The changes in the activity of ATP citrate lyase, which mirrored acetate incorporation, and the effect of glucose and pyruvate on acetate corporation into lipid suggests that some of the lipid synthesis occurs via intramitochondrial acetyl-CoA production from acetate. Despite this, lipid synthesis was not inhibited by (-)-hydroxycitrate. The low rate of synthesis from glucose at two-thirds of gestation is ascribed to the low activity of pyruvate carboxylase at this time and a role for a phosphoenolpyruvate carboxykinase in providing oxaloacetate for lipogenesis is proposed. The activity of fatty acid synthetase broadly agreed with the changes in lipid synthesis, whereas the activity of acetyl-CoA carboxylase was barely sufficient to account for the rates of lipid synthesis in vivo. Acetate and short-chain fatty acids are likely to be the major precursors for lipid synthesis in vivo."}
{"id": "PMID:6016", "title": "Protein phosphorylation in respiring slices of guinea-pig cerebral cortex. Evidence for a role for noradrenaline and adenosine 3':5'-cyclic monophosphate in the increased phosphorylation observed on application of electrical pulses.", "content": "1. Exposure of slices of cerebral cortex from guinea pigs to electrical pulses for 10s or to noradrenaline, 5-hydroxytryptamine or histamine increases the rate of phosphorylation of unidentified proteins in the tissue; the increases in protein phosphorylation due to electrical pulses and noradrenaline were non-additive, whereas the increases due to pulses and 5-hydroxytryptamine or histamine were additive. 2. The stimulating effects of electrical pulses and noradrenaline on protein phosphorylation were antagonized by the beta-adrenergic blocking agents L-propranolol, dichloroisoprenaline, practolol and ICI 66082, but not by the alpha-adrenergic blocking agents, phentolamine and phenoxybenzamine. 3. The increase in protein phosphorylation associated with electrical pulses was antagonized by 10 mum-trifluoperazine and 0.5 mum-prostaglandin E1. 4. It is postulated that under the experimental conditions used the action of electrical pulses on protein phosphorylation is mediated by noradrenaline acting through a beta-adrenergic receptor mechanism probably involving adenylate cyclase.", "contents": "Protein phosphorylation in respiring slices of guinea-pig cerebral cortex. Evidence for a role for noradrenaline and adenosine 3':5'-cyclic monophosphate in the increased phosphorylation observed on application of electrical pulses. 1. Exposure of slices of cerebral cortex from guinea pigs to electrical pulses for 10s or to noradrenaline, 5-hydroxytryptamine or histamine increases the rate of phosphorylation of unidentified proteins in the tissue; the increases in protein phosphorylation due to electrical pulses and noradrenaline were non-additive, whereas the increases due to pulses and 5-hydroxytryptamine or histamine were additive. 2. The stimulating effects of electrical pulses and noradrenaline on protein phosphorylation were antagonized by the beta-adrenergic blocking agents L-propranolol, dichloroisoprenaline, practolol and ICI 66082, but not by the alpha-adrenergic blocking agents, phentolamine and phenoxybenzamine. 3. The increase in protein phosphorylation associated with electrical pulses was antagonized by 10 mum-trifluoperazine and 0.5 mum-prostaglandin E1. 4. It is postulated that under the experimental conditions used the action of electrical pulses on protein phosphorylation is mediated by noradrenaline acting through a beta-adrenergic receptor mechanism probably involving adenylate cyclase."}
{"id": "PMID:6017", "title": "Localization of inhibition by adenosine diphosphate of phosphoglycerate-dependent oxygen evolution in a reconstituted chloroplast system.", "content": "ADP was shown to inhibit phosphoglycerate-dependent O2 evolution in a simplified reconstituted chloroplast system containing 3-phosphoglycerate kinase and triose phosphate dehydrogenase. Rates of O2 evolution in the simplified system are comparable with those obtained by using stromal protein rather than purified enzymes. ADP does not inhibit O2 evolution with glycerate 1,3-biphosphate as substrate nor does it inhibit triose phosphate dehydrogenase. The inhibitory effect of ADP is attributed to an increase in the rate of conversion of glycerate biphosphate into phosphoglycerate. The results are discussed in terms of control by ADP of phosphoglycerate-dependent oxygen evolution.", "contents": "Localization of inhibition by adenosine diphosphate of phosphoglycerate-dependent oxygen evolution in a reconstituted chloroplast system. ADP was shown to inhibit phosphoglycerate-dependent O2 evolution in a simplified reconstituted chloroplast system containing 3-phosphoglycerate kinase and triose phosphate dehydrogenase. Rates of O2 evolution in the simplified system are comparable with those obtained by using stromal protein rather than purified enzymes. ADP does not inhibit O2 evolution with glycerate 1,3-biphosphate as substrate nor does it inhibit triose phosphate dehydrogenase. The inhibitory effect of ADP is attributed to an increase in the rate of conversion of glycerate biphosphate into phosphoglycerate. The results are discussed in terms of control by ADP of phosphoglycerate-dependent oxygen evolution."}
{"id": "PMID:6018", "title": "Regulation of pyruvate dehydrogenase and pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads. Effects of starvation, alloxan-diabetes and high-fat diet.", "content": "1. Pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads was measured by using pig heart pyruvate dehydrogenase [32P]phosphate. About 80% was found to be extramitochondrial and therefore probably not directly concerned with the regulation of pyruvate dehydrogenase activity. The extramitochondrial activity was sensitive to activation by Ca2+, but perhaps less sensitive than the mitochondrial activity.", "contents": "Regulation of pyruvate dehydrogenase and pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads. Effects of starvation, alloxan-diabetes and high-fat diet. 1. Pyruvate dehydrogenase phosphate phosphatase activity in rat epididymal fat-pads was measured by using pig heart pyruvate dehydrogenase [32P]phosphate. About 80% was found to be extramitochondrial and therefore probably not directly concerned with the regulation of pyruvate dehydrogenase activity. The extramitochondrial activity was sensitive to activation by Ca2+, but perhaps less sensitive than the mitochondrial activity."}
{"id": "PMID:6019", "title": "Tyrosine aminotransferase activity in the rabbit placenta. Evidence for decreased inducibility by insulin and cortisol as a function of gestational age.", "content": "Tyrosine aminotransferase is present at low activity in the rabbit placenta. The activity can be enhanced by injecting the pregnant mother with insulin or cortisol. This response decreases over the last half of gestation (14-28 days gestational age).", "contents": "Tyrosine aminotransferase activity in the rabbit placenta. Evidence for decreased inducibility by insulin and cortisol as a function of gestational age. Tyrosine aminotransferase is present at low activity in the rabbit placenta. The activity can be enhanced by injecting the pregnant mother with insulin or cortisol. This response decreases over the last half of gestation (14-28 days gestational age)."}
{"id": "PMID:6020", "title": "Changes in the activities of the enzymes of hepatic fatty acid oxidation during development of the rat.", "content": "1. Changes in the activities of several enzymes involved in mitochondrial fatty acid oxidation were measured in livers of developing rats between late foetal life and maturity. The enzymes studied are medium- and long-chain ATP-dependent acyl-CoA synthetases of the outer mitochondrial membrane and matrix, GTP-dependent acyl-CoA synthetase, carnitine acyltransferase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, general 3-oxoacyl-CoA thiolase and acetoacetyl-CoA thiolase.", "contents": "Changes in the activities of the enzymes of hepatic fatty acid oxidation during development of the rat. 1. Changes in the activities of several enzymes involved in mitochondrial fatty acid oxidation were measured in livers of developing rats between late foetal life and maturity. The enzymes studied are medium- and long-chain ATP-dependent acyl-CoA synthetases of the outer mitochondrial membrane and matrix, GTP-dependent acyl-CoA synthetase, carnitine acyltransferase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, general 3-oxoacyl-CoA thiolase and acetoacetyl-CoA thiolase."}
{"id": "PMID:6039", "title": "Sex differences in anaesthetic toxicity: fluroxene and trifluoroethanol in mice.", "content": "A sex difference in postanaesthetic mortality after fluroxene anaesthesia was found in Swiss Webster mice. More males succumbed than females. This toxicity was biotransformation-dependent and could be reversed by pretreatment with \"opposite\" sex hormones. The toxicity of the fluroxene metabolite trifluoroethanol also was more marked in male mice, but was only partially influenced by microsomal enzyme inhibitors or stimulators, or by sex hormones.", "contents": "Sex differences in anaesthetic toxicity: fluroxene and trifluoroethanol in mice. A sex difference in postanaesthetic mortality after fluroxene anaesthesia was found in Swiss Webster mice. More males succumbed than females. This toxicity was biotransformation-dependent and could be reversed by pretreatment with \"opposite\" sex hormones. The toxicity of the fluroxene metabolite trifluoroethanol also was more marked in male mice, but was only partially influenced by microsomal enzyme inhibitors or stimulators, or by sex hormones."}
{"id": "PMID:6040", "title": "Light-induced membrane potential and pH gradient in Halobacterium halobium envelope vesicles.", "content": "Illumination of envelope vesicles prepared from Halobacterium halobium cells causes translocation of protons from inside to outside, due to the light-induced cycling of bacteriorhodopsin. This process results in a pH gradient across the membranes, an electrical potential, and the movements of K+ and Na+. The electrical potential was estimated by following the fluorescence of a cyanine dye, 3,3'-dipentyloxadicarbocyanine. Illumination of H. halobium vesicles resulted in a rapid, reversible decrease of the dye fluorescence, by as much as 35%. This effect was not seen in nonvesicular patches of purple membrane. Observation of maximal fluorescence decreases upon ilumination of vesicles required an optimal dye/membrane protein ratio. The pH optimum for the lightinduced fluorescence decrease was 6.0. The decrease was linear with actinic light intensity up to about 4 X 10(5) ergs cn-2 s-1. Valinomycin, gramicidin, and triphenylmethylphosphonium ion all abolished the fluorescence changes. However, the light-induced pH change was enhanced by these agents. Conversely, buffered vesicles showed no pH change but gave the same or larger fluorescence changes. Thus, we have identified the fluorescence decrease with a light-induced membrane potential, inside negative. By using valinomycin-K+-induced membrane potentials, we calibrated the fluorescence decrease with calculated Nernst diffusion potentials. We found a linear dependence between potential and fluorescence decrease of 3 mV/%, up to 90 mV. When the envelope vesicles were illuminated, the total proton-motive force generated was dependent on the presence of Na+ and K+ and their concentration gradients across the membrane. In general, K+ appeared to be more permeable than Na+ and, thus, permitted development of greater pH gradients and lower electrical potentials. By calculating the total proton-motive force from the sum of the pH and potential terms, we found that the vesicles can produce proton-motive forces near--200 mV.", "contents": "Light-induced membrane potential and pH gradient in Halobacterium halobium envelope vesicles. Illumination of envelope vesicles prepared from Halobacterium halobium cells causes translocation of protons from inside to outside, due to the light-induced cycling of bacteriorhodopsin. This process results in a pH gradient across the membranes, an electrical potential, and the movements of K+ and Na+. The electrical potential was estimated by following the fluorescence of a cyanine dye, 3,3'-dipentyloxadicarbocyanine. Illumination of H. halobium vesicles resulted in a rapid, reversible decrease of the dye fluorescence, by as much as 35%. This effect was not seen in nonvesicular patches of purple membrane. Observation of maximal fluorescence decreases upon ilumination of vesicles required an optimal dye/membrane protein ratio. The pH optimum for the lightinduced fluorescence decrease was 6.0. The decrease was linear with actinic light intensity up to about 4 X 10(5) ergs cn-2 s-1. Valinomycin, gramicidin, and triphenylmethylphosphonium ion all abolished the fluorescence changes. However, the light-induced pH change was enhanced by these agents. Conversely, buffered vesicles showed no pH change but gave the same or larger fluorescence changes. Thus, we have identified the fluorescence decrease with a light-induced membrane potential, inside negative. By using valinomycin-K+-induced membrane potentials, we calibrated the fluorescence decrease with calculated Nernst diffusion potentials. We found a linear dependence between potential and fluorescence decrease of 3 mV/%, up to 90 mV. When the envelope vesicles were illuminated, the total proton-motive force generated was dependent on the presence of Na+ and K+ and their concentration gradients across the membrane. In general, K+ appeared to be more permeable than Na+ and, thus, permitted development of greater pH gradients and lower electrical potentials. By calculating the total proton-motive force from the sum of the pH and potential terms, we found that the vesicles can produce proton-motive forces near--200 mV."}
{"id": "PMID:6041", "title": "A novel phosphodiesterase from cultured tobacco cells.", "content": "A novel phosphodiesterase was purified from cultured tobacco cells to a state which appeared homogeneous on polyacrylamide gel electrophoresis. The enzyme hydrolyzed various phosphodiester and pyrophosphate bonds, including p-nitrophenyl thymidine 5'-phosphate, p-nitrophenyl thymidine 3'-phosphate, cyclic nucleotides, ATP, NAD+, inorganic pyrophosphate, dinucleotides, and poly(adenosine diphosphate ribose), which is a polymer synthesized from NAD+. However, it did not hydrolyze highly polymerized polynucleotides. The molecular weight of the native enzyme was estimated as 270 000 to 280 000 by gel filtration on Sephadex G-200 and Bio-Gel A-5m. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the enzyme was composed of subunits with molecular weights calculated to be 75 000. The enzyme did not require divalent cations for activity being fully active in the presence of ethylenediaminetetraacetic acid. The pH optimum for the enzyme was approximately 6 with p-ni-trophenyl thymidine 5'-phosphate or adenosine cyclic 3',5'monophosphate, and 5.3 with NAD+. Double reciprocal plots of the initial velocity against the concentration of p-nitrophenyl thymidine 5'-phosphate gave two apparent Km values of 0.17 and 1.3 mM, suggesting the presence of at least two active sites.", "contents": "A novel phosphodiesterase from cultured tobacco cells. A novel phosphodiesterase was purified from cultured tobacco cells to a state which appeared homogeneous on polyacrylamide gel electrophoresis. The enzyme hydrolyzed various phosphodiester and pyrophosphate bonds, including p-nitrophenyl thymidine 5'-phosphate, p-nitrophenyl thymidine 3'-phosphate, cyclic nucleotides, ATP, NAD+, inorganic pyrophosphate, dinucleotides, and poly(adenosine diphosphate ribose), which is a polymer synthesized from NAD+. However, it did not hydrolyze highly polymerized polynucleotides. The molecular weight of the native enzyme was estimated as 270 000 to 280 000 by gel filtration on Sephadex G-200 and Bio-Gel A-5m. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the enzyme was composed of subunits with molecular weights calculated to be 75 000. The enzyme did not require divalent cations for activity being fully active in the presence of ethylenediaminetetraacetic acid. The pH optimum for the enzyme was approximately 6 with p-ni-trophenyl thymidine 5'-phosphate or adenosine cyclic 3',5'monophosphate, and 5.3 with NAD+. Double reciprocal plots of the initial velocity against the concentration of p-nitrophenyl thymidine 5'-phosphate gave two apparent Km values of 0.17 and 1.3 mM, suggesting the presence of at least two active sites."}
{"id": "PMID:6042", "title": "Carbon-13 nuclear magnetic resonance of heme carbonyls. Cytochrome c and carboxymethyl derivatives of cytochrome c.", "content": "Carbonyl complexes of horse cytochrome c and various carboxymethylated derivatives have been examined using 13C NMR (carbon-13 nuclear magnetic resonance) spectroscopy. The multiplicity and chemical shift of the 13CO resonance were found to be functions of pH and the extent of alkylation. Correlations have been made among prominent features of the chemical shift titration curves and changes in the environment of the heme. A simple model compatible with the bulk of previous observations has been suggested to account for the several carbonyl resonance peaks and the complex behavior of the chemical shift with changes in pH.", "contents": "Carbon-13 nuclear magnetic resonance of heme carbonyls. Cytochrome c and carboxymethyl derivatives of cytochrome c. Carbonyl complexes of horse cytochrome c and various carboxymethylated derivatives have been examined using 13C NMR (carbon-13 nuclear magnetic resonance) spectroscopy. The multiplicity and chemical shift of the 13CO resonance were found to be functions of pH and the extent of alkylation. Correlations have been made among prominent features of the chemical shift titration curves and changes in the environment of the heme. A simple model compatible with the bulk of previous observations has been suggested to account for the several carbonyl resonance peaks and the complex behavior of the chemical shift with changes in pH."}
{"id": "PMID:6043", "title": "Complete tyrosine assignments in the high-field 1H nuclear magnetic resonance spectrum of bovine pancreatic trypsin inhibitor selectively reduced and carboxamidomethylated at cystine 14-38.", "content": "The low-field portions of the 250-MHz 1H nuclear magnetic resonance spectra of native and chemically modified basic pancreatic trypsin inhibitor have been studied as a function of pH over the range pH 5-13. In derivatives selectively reduced and carboxamidomethylated at cystine 14-38, resonances associated with 15 of the 16 protons of the aromatic rings of the four tyrosines of the inhibitor have been located and assigned to specific tyrosyl residues. Titrations of pH yielded pK's for tyrosines 10, 21, 23, and 35 in the modified inhibitor of 9.9, 10.6, 11.6, and 11.0, respectively. Resonances associated with the three nitrotyrosine 10 protons of the mononitrated derivative and the six nitrotyrosine 10 and 21 protons of the dinitrated derivative have been similarly located, assigned, and titrated, yielding pK's for nitrotyrosines 10 and 21 of 6.5 and 6.4, respectively. Previously reported results for derivatives with cystine 14-38 intact have been revised on the basis of new data. Comparison of these revised results with the new data for derivatives with modified cystine 14-38 reveals no changes in pK's for any tyrosine or nitrotyrosing ring and no changes in chemical shift for resonances of nitrotyrosine 21 or tyrosines 21 and 23. However, modification of cystine 14-38 causes significant changes in chemical shifts of resonances of the nearby nitrotyrosine 10 and tyrosine 10 and 35 rings. Tyrosine 35 remains relatively immobile, rotating less than 1600 times/s at 25 degrees C for pH's in the range 5-13.", "contents": "Complete tyrosine assignments in the high-field 1H nuclear magnetic resonance spectrum of bovine pancreatic trypsin inhibitor selectively reduced and carboxamidomethylated at cystine 14-38. The low-field portions of the 250-MHz 1H nuclear magnetic resonance spectra of native and chemically modified basic pancreatic trypsin inhibitor have been studied as a function of pH over the range pH 5-13. In derivatives selectively reduced and carboxamidomethylated at cystine 14-38, resonances associated with 15 of the 16 protons of the aromatic rings of the four tyrosines of the inhibitor have been located and assigned to specific tyrosyl residues. Titrations of pH yielded pK's for tyrosines 10, 21, 23, and 35 in the modified inhibitor of 9.9, 10.6, 11.6, and 11.0, respectively. Resonances associated with the three nitrotyrosine 10 protons of the mononitrated derivative and the six nitrotyrosine 10 and 21 protons of the dinitrated derivative have been similarly located, assigned, and titrated, yielding pK's for nitrotyrosines 10 and 21 of 6.5 and 6.4, respectively. Previously reported results for derivatives with cystine 14-38 intact have been revised on the basis of new data. Comparison of these revised results with the new data for derivatives with modified cystine 14-38 reveals no changes in pK's for any tyrosine or nitrotyrosing ring and no changes in chemical shift for resonances of nitrotyrosine 21 or tyrosines 21 and 23. However, modification of cystine 14-38 causes significant changes in chemical shifts of resonances of the nearby nitrotyrosine 10 and tyrosine 10 and 35 rings. Tyrosine 35 remains relatively immobile, rotating less than 1600 times/s at 25 degrees C for pH's in the range 5-13."}
{"id": "PMID:6044", "title": "The pH dependence of the conformation of angiotensin peptides by nuclear magnetic resonance: cis-trans isomerism of proline 7.", "content": "The pH dependence of the proton NMR spectrum of [Asn1, Val5] angiotensin II in aqueous solution shows the existence of one major and one minor conformation above pH 6.5, the minor conformation representing 12 +/- 2% of the total peptide. A similar observation has been made for (Asn1, Val5) angiotensin I and Val-Tyr-Val-His-Pro-Phe. This effect is not due to the presence of angiotensin-like impurities in the peptide samples. We have shown two expected impurities, [beta-Asp1, Val5] angiotensin II and [Asn1, 3-Bzl-Ty4, Val5] - angiotensin II, to be absent, and a third impurity [Asn1, Val5, D-His6] angiostensin II, to be present at less than or equal to 2.1 mol%, too little to account for the observed amount (12 +/- 2%) of minor conformation. The carbon-13 spectrum of the hexapeptide at high pH shows that the major conformation has Pro7 in the trans form and the minor conformation has Pro7 in the cis form.", "contents": "The pH dependence of the conformation of angiotensin peptides by nuclear magnetic resonance: cis-trans isomerism of proline 7. The pH dependence of the proton NMR spectrum of [Asn1, Val5] angiotensin II in aqueous solution shows the existence of one major and one minor conformation above pH 6.5, the minor conformation representing 12 +/- 2% of the total peptide. A similar observation has been made for (Asn1, Val5) angiotensin I and Val-Tyr-Val-His-Pro-Phe. This effect is not due to the presence of angiotensin-like impurities in the peptide samples. We have shown two expected impurities, [beta-Asp1, Val5] angiotensin II and [Asn1, 3-Bzl-Ty4, Val5] - angiotensin II, to be absent, and a third impurity [Asn1, Val5, D-His6] angiostensin II, to be present at less than or equal to 2.1 mol%, too little to account for the observed amount (12 +/- 2%) of minor conformation. The carbon-13 spectrum of the hexapeptide at high pH shows that the major conformation has Pro7 in the trans form and the minor conformation has Pro7 in the cis form."}
{"id": "PMID:6045", "title": "Stereochemical analysis of the elimination reaction catalyzed by D-amino-acid oxidase.", "content": "The stereochemistry of the intramolecular proton transfer catalyzed by the flavoenzyme, D-amino-acid oxidase, during the elimination reaction of beta-chloro-alpha-amino acid substrates (Walsh et al. (1973), J. Biol. Chem. 248, 1964) has been established. Both D-erythro- and D-threo-2-amino-3-chloro(2-3H) butyrate have been shown to yield (3R)-2-keto (3-3H)-2- butyrate predominantly. Tritium kinetic isotope effects on the rate of the reaction (4.7 for the D-erythro, and 3.8 for the D-threo compound) and percentages of intramolecular triton transfer (7.2% for the D-erythro- and 2.6% for the D-threo compound) have been measured. Their implications on the mechanism of this unusual elimination reaction are discussed.", "contents": "Stereochemical analysis of the elimination reaction catalyzed by D-amino-acid oxidase. The stereochemistry of the intramolecular proton transfer catalyzed by the flavoenzyme, D-amino-acid oxidase, during the elimination reaction of beta-chloro-alpha-amino acid substrates (Walsh et al. (1973), J. Biol. Chem. 248, 1964) has been established. Both D-erythro- and D-threo-2-amino-3-chloro(2-3H) butyrate have been shown to yield (3R)-2-keto (3-3H)-2- butyrate predominantly. Tritium kinetic isotope effects on the rate of the reaction (4.7 for the D-erythro, and 3.8 for the D-threo compound) and percentages of intramolecular triton transfer (7.2% for the D-erythro- and 2.6% for the D-threo compound) have been measured. Their implications on the mechanism of this unusual elimination reaction are discussed."}
{"id": "PMID:6047", "title": "The subcellular distribution and partial characterization of cholinesterase activities of canine platelets.", "content": "The multiple cholinesterase activities in canine platelets have been investigated. Platelets were homogenized by rapid decompression under nitrogen, glass tube/Teflon pestle, and glycerol lysis techniques. Rapid decompression under nitrogen technique was found to be the most efficient and gentle method for cell disruption. Homogenates were subfractionated using sodium diatrizoate density gradients. Marker enzyme assays and pulse labeling experiments with 5-hydroxyl[14C] tryptamine and [125I] thrombin on prepared subcellular fractions confirmed that the soluble, plasma membrane and the granule-1 fractions were all in reasonably pure form. Furthermore, labeling of the plasma membrane with [125I] thrombin is cited as the first successful attempt at attaining significantly bound marker for this structure. Cholinesterase activity distributions measured in these fractions indicated that about 30% of the activity was present in the plasma membrane, 50% in granule-1 and 5% in soluble fractions. Kinetic data of cholinesterase activities obtained from intact platelets, plasma membrane preparations and platelet release supernatants indicated that they are strikingly similar.", "contents": "The subcellular distribution and partial characterization of cholinesterase activities of canine platelets. The multiple cholinesterase activities in canine platelets have been investigated. Platelets were homogenized by rapid decompression under nitrogen, glass tube/Teflon pestle, and glycerol lysis techniques. Rapid decompression under nitrogen technique was found to be the most efficient and gentle method for cell disruption. Homogenates were subfractionated using sodium diatrizoate density gradients. Marker enzyme assays and pulse labeling experiments with 5-hydroxyl[14C] tryptamine and [125I] thrombin on prepared subcellular fractions confirmed that the soluble, plasma membrane and the granule-1 fractions were all in reasonably pure form. Furthermore, labeling of the plasma membrane with [125I] thrombin is cited as the first successful attempt at attaining significantly bound marker for this structure. Cholinesterase activity distributions measured in these fractions indicated that about 30% of the activity was present in the plasma membrane, 50% in granule-1 and 5% in soluble fractions. Kinetic data of cholinesterase activities obtained from intact platelets, plasma membrane preparations and platelet release supernatants indicated that they are strikingly similar."}
{"id": "PMID:6048", "title": "Effect of Ca2+, ruthenium red and ageing on pregnenolone production by mitochondrial fractions from normal and luteinizing hormone treated rat testes.", "content": "The effect of Ca2+ in vitro on pregnenolone production rates under various incubation conditions by mitochondrial fractions isolated from testes of normal rats and of rats after in vivo treatment with luteinizing hormone has been investigated. Concentrations of Ca2+ in the range of 0.1-0.5 mM stimulated succinate supported pregnenolone production in mitochondrial fractions from both control and luteinizing hormone treated testes. When mitochondrial fractions were isolated in 0.25 M sucrose without additions, Ca2+ in vitro increased succinate supported pregnenolone production rates in mitochondrial fractions isolated from control testes to a greater extent than in mitochondrial fractions, from luteinizing hormone treated testes. Production rates in control mitochondrial fraction, incubated in the presence of initial Ca2+ concentrations of 0.7 mM and higher were almost similar to production rates in relevant luteinizing hormone treated mitochondria.", "contents": "Effect of Ca2+, ruthenium red and ageing on pregnenolone production by mitochondrial fractions from normal and luteinizing hormone treated rat testes. The effect of Ca2+ in vitro on pregnenolone production rates under various incubation conditions by mitochondrial fractions isolated from testes of normal rats and of rats after in vivo treatment with luteinizing hormone has been investigated. Concentrations of Ca2+ in the range of 0.1-0.5 mM stimulated succinate supported pregnenolone production in mitochondrial fractions from both control and luteinizing hormone treated testes. When mitochondrial fractions were isolated in 0.25 M sucrose without additions, Ca2+ in vitro increased succinate supported pregnenolone production rates in mitochondrial fractions isolated from control testes to a greater extent than in mitochondrial fractions, from luteinizing hormone treated testes. Production rates in control mitochondrial fraction, incubated in the presence of initial Ca2+ concentrations of 0.7 mM and higher were almost similar to production rates in relevant luteinizing hormone treated mitochondria."}
{"id": "PMID:6049", "title": "Subcellular localizations of guanylate cyclase and 3',5'-cyclic nucleotide phosphodiesterase in sea urchin sperm.", "content": "The subcellular localizations of guanylate cyclase and 3',5'-cyclic nucleotide phosphodiesterase in sea urchin sperm were examined. Both the specific and total activities of these two enzymes were much higher in sperm flagella (tails) than in the heads. In addition to the observation that guanylate cyclase in the flagella was particulate-bound and solubilized by Triton X-100, more than 80% of the cyclase activity in the flagella was found in the plasma membrane fraction, whereas the activity of cyclic nucleotide phosphodiesterase was observed in both the axonemal and plasma membrane fractions. The observations indicated that the cyclase in the flagella appeared to be associated with the plasma membrane. Cyclic nucleotide phosphodiesterase in the plasma membrane fraction as well as the axonemal fraction hydrolyzed both cyclic GMP and cyclic AMP; however, the rates of hydrolysis for cyclic GMP were obviously higher than those for cyclic AMP. The enzymic properties of guanylate cyclase and cyclic nucleotide phosphodiesterase in sperm flagella were also briefly described.", "contents": "Subcellular localizations of guanylate cyclase and 3',5'-cyclic nucleotide phosphodiesterase in sea urchin sperm. The subcellular localizations of guanylate cyclase and 3',5'-cyclic nucleotide phosphodiesterase in sea urchin sperm were examined. Both the specific and total activities of these two enzymes were much higher in sperm flagella (tails) than in the heads. In addition to the observation that guanylate cyclase in the flagella was particulate-bound and solubilized by Triton X-100, more than 80% of the cyclase activity in the flagella was found in the plasma membrane fraction, whereas the activity of cyclic nucleotide phosphodiesterase was observed in both the axonemal and plasma membrane fractions. The observations indicated that the cyclase in the flagella appeared to be associated with the plasma membrane. Cyclic nucleotide phosphodiesterase in the plasma membrane fraction as well as the axonemal fraction hydrolyzed both cyclic GMP and cyclic AMP; however, the rates of hydrolysis for cyclic GMP were obviously higher than those for cyclic AMP. The enzymic properties of guanylate cyclase and cyclic nucleotide phosphodiesterase in sperm flagella were also briefly described."}
{"id": "PMID:6050", "title": "Transport and utilization of the biosynthetic intermediate shikimic acid in Escherichia coli.", "content": "Auxotrophic mutants of Escherichia coli W or K12 blocked before shikimic acid in the aromatic biosynthetic pathway grew poorly on shikimic acid as sole aromatic supplement. This poor growth response was correlated with a relatively poor ability to transport shikimic acid. If citrate was present in the growth medium (as it is in some commonly used basal media) the growth of some of the E. coli K12 mutants on shikimate was further reduced. Mutants were derived from pre-shikimate auxotrophs which grew rapidly on media containing shikimic acid. These derivatives all had an increased ability to transport shikimic acid. Thus, it is proposed that the growth on shikimate observed in the parent cells is restricted by their relatively poor uptake of shikimate from the medium and that this restriction may be removed by a mutation which enhances shikimate transport. Transduction analysis of the mutations which enhanced utilization and transport of shikimic acid by E. coli K12 strains indicated at least two classes. Class 1 was about 20% cotransduced with the histidine region of the E. coli K12 chromosome and appeared to be coincident with a known shikimate transport locus, shiA. Class 2 was not cotransduced with his. The locus (or loci) of this class is unknown. Kinetic measurements suggested that both classes had shikimate uptake systems derived from the wild-type system. Two class 1 mutants had increased levels of otherwise unaltered wild-type transport while one class 2 mutant had an altered Michaelis constant (Km) for shikimate transport.", "contents": "Transport and utilization of the biosynthetic intermediate shikimic acid in Escherichia coli. Auxotrophic mutants of Escherichia coli W or K12 blocked before shikimic acid in the aromatic biosynthetic pathway grew poorly on shikimic acid as sole aromatic supplement. This poor growth response was correlated with a relatively poor ability to transport shikimic acid. If citrate was present in the growth medium (as it is in some commonly used basal media) the growth of some of the E. coli K12 mutants on shikimate was further reduced. Mutants were derived from pre-shikimate auxotrophs which grew rapidly on media containing shikimic acid. These derivatives all had an increased ability to transport shikimic acid. Thus, it is proposed that the growth on shikimate observed in the parent cells is restricted by their relatively poor uptake of shikimate from the medium and that this restriction may be removed by a mutation which enhances shikimate transport. Transduction analysis of the mutations which enhanced utilization and transport of shikimic acid by E. coli K12 strains indicated at least two classes. Class 1 was about 20% cotransduced with the histidine region of the E. coli K12 chromosome and appeared to be coincident with a known shikimate transport locus, shiA. Class 2 was not cotransduced with his. The locus (or loci) of this class is unknown. Kinetic measurements suggested that both classes had shikimate uptake systems derived from the wild-type system. Two class 1 mutants had increased levels of otherwise unaltered wild-type transport while one class 2 mutant had an altered Michaelis constant (Km) for shikimate transport."}
{"id": "PMID:6051", "title": "Enzymatic synthesis of 2-O-alpha-D-mannopyranosyl-methyl-alpha-D-mannopyranoside by a cell-free particulate system of Mycobacterium smegmatis.", "content": "A cell-free particulate enzyme preparation of Mycobacterium smegmatis ATCC 607 catalyzed the transfer of labeled mannose from GDP[14C] mannose to methyl-alpha-D-mannopyranoside (an exogenously added acceptor) to form a product that was characterized to be 2-O-alpha-D[14C] mannopyranosyl-methyl-alpha-D-mannopyranoside. This transmannosylase activity was specific for both the sugar nucleotide donor and methyl monosaccharide acceptor. The reaction was stimulated by the addition of various metal ions and had a pH optimum of 6.0. The apparent Km of this transmannosylase reaction for methyl-alpha-D-mannopyranoside was 35 mM. The possible relationship between this \"artificial\" mannosyl-transfer system and the \"natural\" system which leads to the formation of the oligomannosides and glycoproteins is discussed.", "contents": "Enzymatic synthesis of 2-O-alpha-D-mannopyranosyl-methyl-alpha-D-mannopyranoside by a cell-free particulate system of Mycobacterium smegmatis. A cell-free particulate enzyme preparation of Mycobacterium smegmatis ATCC 607 catalyzed the transfer of labeled mannose from GDP[14C] mannose to methyl-alpha-D-mannopyranoside (an exogenously added acceptor) to form a product that was characterized to be 2-O-alpha-D[14C] mannopyranosyl-methyl-alpha-D-mannopyranoside. This transmannosylase activity was specific for both the sugar nucleotide donor and methyl monosaccharide acceptor. The reaction was stimulated by the addition of various metal ions and had a pH optimum of 6.0. The apparent Km of this transmannosylase reaction for methyl-alpha-D-mannopyranoside was 35 mM. The possible relationship between this \"artificial\" mannosyl-transfer system and the \"natural\" system which leads to the formation of the oligomannosides and glycoproteins is discussed."}
{"id": "PMID:6052", "title": "Biosynthesis of yeast mannan. Diversity of mannosyltransferases in the mannan-synthesizing enzyme system from yeast.", "content": "1. A microsomal enzyme preparation from the yeast Saccharomyces cerevisiae catalyzes the transfer of mannosyl units from GDPmannose to mannose and a number of mannose-containing oligosaccharides and glycosides whereby different glycosidic bonds are formed. 2. Of the compounds tested besides mannose, only those containing an alpha-linked mannosyl unit at the nonreducing position of their molecule were effective as acceptors. Monodeoxyanalogues of mannose as well as alpha-mannose phosphates did not serve as acceptors in the above reaction. 3. The structure of the product formed with mannose as acceptor was determined to be O-alpha-D-mannosyl-(1 leads to 2)-mannose; with alphaMan (1 leads to 6)mannose as the acceptor, the product was alphaMan(1 leads to 6)mannose and with alphaMan-(1 leads to 2)mannose the product was tentatively characterized as a mixture of alphaMan-(1 leads to 3)alphaMan(1 leads to 2)mannose and alphaMan(1 leads to 2)alphaMan(1 leads to 2)mannose. 4. The enzymes catalyzing the formation of different types of glycosidic bonds differed in their acceptor specificity, pH-activity curves and rates of heat denaturation. 5. Radioactive disaccharides were unable to enter the mannan protein molecule in the cell-free system while free radioactive mannose did incorporate into polysaccharide to a minor extent under the same conditions.", "contents": "Biosynthesis of yeast mannan. Diversity of mannosyltransferases in the mannan-synthesizing enzyme system from yeast. 1. A microsomal enzyme preparation from the yeast Saccharomyces cerevisiae catalyzes the transfer of mannosyl units from GDPmannose to mannose and a number of mannose-containing oligosaccharides and glycosides whereby different glycosidic bonds are formed. 2. Of the compounds tested besides mannose, only those containing an alpha-linked mannosyl unit at the nonreducing position of their molecule were effective as acceptors. Monodeoxyanalogues of mannose as well as alpha-mannose phosphates did not serve as acceptors in the above reaction. 3. The structure of the product formed with mannose as acceptor was determined to be O-alpha-D-mannosyl-(1 leads to 2)-mannose; with alphaMan (1 leads to 6)mannose as the acceptor, the product was alphaMan(1 leads to 6)mannose and with alphaMan-(1 leads to 2)mannose the product was tentatively characterized as a mixture of alphaMan-(1 leads to 3)alphaMan(1 leads to 2)mannose and alphaMan(1 leads to 2)alphaMan(1 leads to 2)mannose. 4. The enzymes catalyzing the formation of different types of glycosidic bonds differed in their acceptor specificity, pH-activity curves and rates of heat denaturation. 5. Radioactive disaccharides were unable to enter the mannan protein molecule in the cell-free system while free radioactive mannose did incorporate into polysaccharide to a minor extent under the same conditions."}
{"id": "PMID:6053", "title": "Regulation of 6-hydroxy-2,4,5-triaminopyrimidine synthesis by riboflavin and iron in riboflavin-deficient mutants of Pichia guilliermondii yeast.", "content": "The effect of riboflavin and iron on 6-hydroxy-2,4,5-triaminopyrimidine synthesis rate was investigated in the cultures of the yeast Pichia guilliermondii (rib2 mutants) with the blocked second reaction to flavinogenesis. It was shown that riboflavin inhibited the 6-hydroxy-2,4,5-triaminopyrimidine synthesis rate in iron-rich and iron-deficient cells of mutants with low riboflavin requirements. Cycloheximide did not prevent the stimulation of 6-hydroxy-2,4,5-triaminopyrimidine synthesis caused by riboflavin starvation. 7-methyl-8-trifluoromethyl-10-(1'-D-ribityl)isoalloxazine strongly inhibited the 6-hydroxy-2,4,5-triaminopyrimidine synthesis, while 7-methyl-8-trifluoro-methyl-10-(beta-hydroxyethyl)izoalloxazine and galactoflavin exerted only a slight effect on this process. The 6-hydroxy-2,4,5-triaminopyrimidine synthesis rate in iron-deficient cells was significantly higher than in iron-rich cells. The 2,2'-dipyridyl treatment of iron-rich cells caused the stimulation of 6-hydroxy-2,4,5-triaminopyrimidine synthesis and cycloheximide abolished this effect. The results suggest that the activity of the first enzyme of flavinogenesis (guanylic cyclohydrolase) is under the control of feedback inhibition by flavins and the biosynthesis of this enzyme is regulated by iron.", "contents": "Regulation of 6-hydroxy-2,4,5-triaminopyrimidine synthesis by riboflavin and iron in riboflavin-deficient mutants of Pichia guilliermondii yeast. The effect of riboflavin and iron on 6-hydroxy-2,4,5-triaminopyrimidine synthesis rate was investigated in the cultures of the yeast Pichia guilliermondii (rib2 mutants) with the blocked second reaction to flavinogenesis. It was shown that riboflavin inhibited the 6-hydroxy-2,4,5-triaminopyrimidine synthesis rate in iron-rich and iron-deficient cells of mutants with low riboflavin requirements. Cycloheximide did not prevent the stimulation of 6-hydroxy-2,4,5-triaminopyrimidine synthesis caused by riboflavin starvation. 7-methyl-8-trifluoromethyl-10-(1'-D-ribityl)isoalloxazine strongly inhibited the 6-hydroxy-2,4,5-triaminopyrimidine synthesis, while 7-methyl-8-trifluoro-methyl-10-(beta-hydroxyethyl)izoalloxazine and galactoflavin exerted only a slight effect on this process. The 6-hydroxy-2,4,5-triaminopyrimidine synthesis rate in iron-deficient cells was significantly higher than in iron-rich cells. The 2,2'-dipyridyl treatment of iron-rich cells caused the stimulation of 6-hydroxy-2,4,5-triaminopyrimidine synthesis and cycloheximide abolished this effect. The results suggest that the activity of the first enzyme of flavinogenesis (guanylic cyclohydrolase) is under the control of feedback inhibition by flavins and the biosynthesis of this enzyme is regulated by iron."}
{"id": "PMID:6054", "title": "Resistance of Pediococcus cerevisiae to amethopterin as a consequence of changes in enzymatic activity and cell permeability. I. Dihydrofolate reductase, thymidylate synthetase and formyltetrahydrofolate synthetase in amethopterin-resistant and -sensitive strains of Pediococcus cerevisiae.", "content": "Pediococcus cerevisiae/AMr, resistant to amethopterin, possesses a higher dihydrofolate reductase (5, 6, 7, 8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) activity than the parent, a folate-permeable and thus amethopterin-susceptible strain and than the wild-type. The properties of dihydrofolate reductase from the three strains have been compared. Temperature, pH optima, heat stability, as well amethopterin binding did not reveal significant differences between the enzymes from the susceptible and resistant strains. The enzyme from the wild-type was 10 times more sensitive to inhibition by amethopterin and more susceptible to heat denaturation. The apparent Km values for dihydrofolate in enzymes from the three strains were in the range of 4.8--7.2 muM and for NADPH 6.5--8.0 muM. The amethopterin-resistant strain exhibited cross-resistance to trimethoprim and was about 40-fold more resistant to the latter than the sensitive parent and the wild-type.  The resistance to trimethoprim appears to be a direct result of the increased dihydrofolate reductase activity. Inhibition of dihydrofolate reductase activity by this drug was similar in the three strains. 10--20 nmol caused 50% inhibition of 0.02 enzyme unit. Trimethoprim was about 10 000 times less effective inhibitor of dihydrofolate reductase than amethopterin. The cell extract of the AMr strain possessed a folate reductase activity three times higher than that of the sensitive strain. The activities of other folate-related enzymes like thymidylate synthetase and 10-formyltetrahydrofolate synthetase (formate: tetrahydrofolate ligase (ADP-forming), EC 6.3.4.3) were similar in the three strains studied.", "contents": "Resistance of Pediococcus cerevisiae to amethopterin as a consequence of changes in enzymatic activity and cell permeability. I. Dihydrofolate reductase, thymidylate synthetase and formyltetrahydrofolate synthetase in amethopterin-resistant and -sensitive strains of Pediococcus cerevisiae. Pediococcus cerevisiae/AMr, resistant to amethopterin, possesses a higher dihydrofolate reductase (5, 6, 7, 8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) activity than the parent, a folate-permeable and thus amethopterin-susceptible strain and than the wild-type. The properties of dihydrofolate reductase from the three strains have been compared. Temperature, pH optima, heat stability, as well amethopterin binding did not reveal significant differences between the enzymes from the susceptible and resistant strains. The enzyme from the wild-type was 10 times more sensitive to inhibition by amethopterin and more susceptible to heat denaturation. The apparent Km values for dihydrofolate in enzymes from the three strains were in the range of 4.8--7.2 muM and for NADPH 6.5--8.0 muM. The amethopterin-resistant strain exhibited cross-resistance to trimethoprim and was about 40-fold more resistant to the latter than the sensitive parent and the wild-type.  The resistance to trimethoprim appears to be a direct result of the increased dihydrofolate reductase activity. Inhibition of dihydrofolate reductase activity by this drug was similar in the three strains. 10--20 nmol caused 50% inhibition of 0.02 enzyme unit. Trimethoprim was about 10 000 times less effective inhibitor of dihydrofolate reductase than amethopterin. The cell extract of the AMr strain possessed a folate reductase activity three times higher than that of the sensitive strain. The activities of other folate-related enzymes like thymidylate synthetase and 10-formyltetrahydrofolate synthetase (formate: tetrahydrofolate ligase (ADP-forming), EC 6.3.4.3) were similar in the three strains studied."}
{"id": "PMID:6055", "title": "Resistance to Pediococcus cerevisiae to amethopterin as a consequence of changes in enzymatic activity and cell permeability. II. Permeability changes to amethopterin and other folates in the drug-resistant mutant.", "content": "the accumulation of amethopterin in a Pediococcus cerevisiae strain resistant to this analogue was about 30% of that in P. cerevisiae/PteGlu, the sensitive parent. The uptake in the resistant strain was strictly glucose dependent, whereas in the sensitive parent about 16% accumulation occurred in absence of glucose. The transport in both strains was inhibited by iodoacetate and KF. Amethopterin uptake exhibited saturation kinetics with an apparent Km of 5 muM in P. cerevisiae/AMr and 0.5 muM in P. cerevisiae/PteGlu. The apparent V was 0.2 nmol per min per mg cells (dry weight); the same for both strains. The optimum pH for the uptake of amethopterin by P. cerevisiae/AMr and P. cerevisiae/PteGlu was pH 6.0. Folate and methyltetrahydrofolate competitivity inhibited amethopterin uptake with apparent Ki values of 8 and 0.7 muM, respectively. The uptake of folate exhibited a slightly increased Km value as compared to that of the sensitive strain, whereas the uptake activity velocity was in the same range. Methyltetrahydrofolate accumulated up to about 60-fold higher intracellular concentration than that of the medium, which is a markedly lower accumulation from that in the sensitive strain. The uptake was glucose dependent and inhibited by iodoacetate and KF. The pH optimum for methyltetrahydrofolate uptake in the resistant strain was the same as that in the sensitive parent (pH 5.7--6). In contrast to the increase in the apparent Km value for amethopterin in the resistant strain, the affinity of the carrier for methyltetrahydrofolate was apparently unchanged, whereas the V value was about 16 times lower than that in the sensitive strain. The Ki for amethopterin when added to increasing concentrations of methyltetrahydrofolate was 5.2 muM, a value about the same as that of the Km.", "contents": "Resistance to Pediococcus cerevisiae to amethopterin as a consequence of changes in enzymatic activity and cell permeability. II. Permeability changes to amethopterin and other folates in the drug-resistant mutant. the accumulation of amethopterin in a Pediococcus cerevisiae strain resistant to this analogue was about 30% of that in P. cerevisiae/PteGlu, the sensitive parent. The uptake in the resistant strain was strictly glucose dependent, whereas in the sensitive parent about 16% accumulation occurred in absence of glucose. The transport in both strains was inhibited by iodoacetate and KF. Amethopterin uptake exhibited saturation kinetics with an apparent Km of 5 muM in P. cerevisiae/AMr and 0.5 muM in P. cerevisiae/PteGlu. The apparent V was 0.2 nmol per min per mg cells (dry weight); the same for both strains. The optimum pH for the uptake of amethopterin by P. cerevisiae/AMr and P. cerevisiae/PteGlu was pH 6.0. Folate and methyltetrahydrofolate competitivity inhibited amethopterin uptake with apparent Ki values of 8 and 0.7 muM, respectively. The uptake of folate exhibited a slightly increased Km value as compared to that of the sensitive strain, whereas the uptake activity velocity was in the same range. Methyltetrahydrofolate accumulated up to about 60-fold higher intracellular concentration than that of the medium, which is a markedly lower accumulation from that in the sensitive strain. The uptake was glucose dependent and inhibited by iodoacetate and KF. The pH optimum for methyltetrahydrofolate uptake in the resistant strain was the same as that in the sensitive parent (pH 5.7--6). In contrast to the increase in the apparent Km value for amethopterin in the resistant strain, the affinity of the carrier for methyltetrahydrofolate was apparently unchanged, whereas the V value was about 16 times lower than that in the sensitive strain. The Ki for amethopterin when added to increasing concentrations of methyltetrahydrofolate was 5.2 muM, a value about the same as that of the Km."}
{"id": "PMID:6056", "title": "The interaction between vitamin B-12 and micelles in aqueous solution.", "content": "The apparent pK for benzimidazole displacement of a number of cobalamins is markedly affected by the presence of sodium lauryl sulfate micelles. However, micelles of cetyltrimethylammonium bromide or Triton X have little or no effect on the pK. By measuring the apparent pK as a function of sodium lauryl sulfate concentration, the association constants between the micelles and both base on and base off methylcobalamin were calculated. This calculation indicates that the base off form is strongly associated with the micelle while the base on form is not.", "contents": "The interaction between vitamin B-12 and micelles in aqueous solution. The apparent pK for benzimidazole displacement of a number of cobalamins is markedly affected by the presence of sodium lauryl sulfate micelles. However, micelles of cetyltrimethylammonium bromide or Triton X have little or no effect on the pK. By measuring the apparent pK as a function of sodium lauryl sulfate concentration, the association constants between the micelles and both base on and base off methylcobalamin were calculated. This calculation indicates that the base off form is strongly associated with the micelle while the base on form is not."}
{"id": "PMID:6057", "title": "Functional heterogeneity and pH-dependent dissociation properties of human transferrin.", "content": "Human diferric transferrin was partially labeled with 59Fe at low or neutral pH (chemically labeled) and by replacement of diferric iron previously donated to rabbit reticulocytes (biologically labeled). Reticulocyte 59Fe uptake experiments with chemically labeled preparations indicated that iron bound at near neutral pH was more readily incorporated by reticulocytes than iron bound at low pH. The pH-dependent iron dissociation studies of biologically labeled transferrin solutions indicated that Fe3+, bound at the site from which the metal was initially utilized by the cells, dissociated between pH 5.8 and 7.4. In contrast, lower pH (5.2--5.8) was required to effect dissociation of iron that has remained bound to the protein after incubation with reticulocytes. These findings suggest that each human transferrin iron-binding site has different acid-base iron-binding properties which could be related to the observed heterogenic rabbit reticulocyte iron-donating properties of human transferrin and identifies that the near neutral iron-binding site initially surrenders its iron to these cells.", "contents": "Functional heterogeneity and pH-dependent dissociation properties of human transferrin. Human diferric transferrin was partially labeled with 59Fe at low or neutral pH (chemically labeled) and by replacement of diferric iron previously donated to rabbit reticulocytes (biologically labeled). Reticulocyte 59Fe uptake experiments with chemically labeled preparations indicated that iron bound at near neutral pH was more readily incorporated by reticulocytes than iron bound at low pH. The pH-dependent iron dissociation studies of biologically labeled transferrin solutions indicated that Fe3+, bound at the site from which the metal was initially utilized by the cells, dissociated between pH 5.8 and 7.4. In contrast, lower pH (5.2--5.8) was required to effect dissociation of iron that has remained bound to the protein after incubation with reticulocytes. These findings suggest that each human transferrin iron-binding site has different acid-base iron-binding properties which could be related to the observed heterogenic rabbit reticulocyte iron-donating properties of human transferrin and identifies that the near neutral iron-binding site initially surrenders its iron to these cells."}
{"id": "PMID:6058", "title": "pH dependence of the oxidation-reduction potential of cytochrome c2.", "content": "The pH dependence of the spectra and of the oxidation-reduction potential of three cytochromes c2, from Rhodopseudomonas capsulata, Rhodopseudomonas sphaeroides and Rhodomicrobium vannielii, were studied. A single alkaline pK was observed for the spectral changes in all three ferricytochromes. In Rps. capsulata cytochrome c2 this spectroscopic pK corresponds to the pK observed in the dependence of oxidation-reduction potential on pH. For the other two cytochromes the oxidation-reduction potential showed a complex dependency on pH which can be fitted to theoretical curves involving three ionizations. The third ionization corresponds to the ionization observed in the spectroscopic studies but the first two occur without changes in the visible spectra. The possible structural bases for these ionizations are discussed.", "contents": "pH dependence of the oxidation-reduction potential of cytochrome c2. The pH dependence of the spectra and of the oxidation-reduction potential of three cytochromes c2, from Rhodopseudomonas capsulata, Rhodopseudomonas sphaeroides and Rhodomicrobium vannielii, were studied. A single alkaline pK was observed for the spectral changes in all three ferricytochromes. In Rps. capsulata cytochrome c2 this spectroscopic pK corresponds to the pK observed in the dependence of oxidation-reduction potential on pH. For the other two cytochromes the oxidation-reduction potential showed a complex dependency on pH which can be fitted to theoretical curves involving three ionizations. The third ionization corresponds to the ionization observed in the spectroscopic studies but the first two occur without changes in the visible spectra. The possible structural bases for these ionizations are discussed."}
{"id": "PMID:6060", "title": "Iron-sulfur proteins of the green photosynthetic bacterium Chlorobium.", "content": "The iron-sulfur proteins of the green photosynthetic bacterium Chlorobium have been characterized by oxidation-reduction potentiometry in conjunction with low-temperature electron paramagnetic resonance spectroscopy. Chlorobium ferredoxin was the only iron-sulfur protein detected in the soluble fraction; no high-potential iron-sulfur protein was observed. In addition, high-potential iron-sulfur protein was not detected in the chromatophores. Four chromatophore-bound iron-sulfur proteins were detected. One is the \"Rieske\" type iron-sulfur protein with a g-value of 1.90 in the reduced state; the protein has a midpoint potential of + 160 mV (pH 7.0), and this potential is pH dependent. Three g=1.94 chromatophore-bound iron-sulfur proteins were observed, with midpoint potentials of -25, -175, and about -550 mV. A possible role for the latter iron-sulfur protein in the primary photochemical reaction in Chlorobium is considered.", "contents": "Iron-sulfur proteins of the green photosynthetic bacterium Chlorobium. The iron-sulfur proteins of the green photosynthetic bacterium Chlorobium have been characterized by oxidation-reduction potentiometry in conjunction with low-temperature electron paramagnetic resonance spectroscopy. Chlorobium ferredoxin was the only iron-sulfur protein detected in the soluble fraction; no high-potential iron-sulfur protein was observed. In addition, high-potential iron-sulfur protein was not detected in the chromatophores. Four chromatophore-bound iron-sulfur proteins were detected. One is the \"Rieske\" type iron-sulfur protein with a g-value of 1.90 in the reduced state; the protein has a midpoint potential of + 160 mV (pH 7.0), and this potential is pH dependent. Three g=1.94 chromatophore-bound iron-sulfur proteins were observed, with midpoint potentials of -25, -175, and about -550 mV. A possible role for the latter iron-sulfur protein in the primary photochemical reaction in Chlorobium is considered."}
{"id": "PMID:6061", "title": "Binding of fluorescent lanthanides to rat liver mitochondrial membranes and calcium ion-binding proteins.", "content": "(1) Tb3+ binding to mitochondrial membranes can be monitored by enhanced ion fluorescence at 545 nm with excitation at 285 nm. At low protein concentrations (less than 30 mug/ml) no inner filter effects are observed. (2) This binding is localized at the external surface of the inner membrane and is unaffected by inhibitors of respiration or oxidative phosphorylation. (3) A soluble Ca2+ binding protein isolated according to Lehninger, A.L. ((1971) Biochem. Biophys. Res. Commun. 42, 312-317) also binds Tb3+ with enhanced ion fluorescence upon excitation at 285 nm. The excitation spectrum of the isolated protein and of the intact mitochondria are indicative of an aromatic amino acid at the cation binding site. (4) Further characterization of the Tb3+-protein interaction revealed that there is more than one binding site per protein molecule and that these sites are clustered (less than 20 A). Neuraminidase treatment or organic solvent extraction of the protein did not affect fluorescent Tb3+ binding. (5) pH dependency studies of Tb3+ binding to the isolated protein or intact mitochondria demonstrated the importance of an ionizable group of pK greater than 6. At pH less than 7.5 the amount of Tb3+ bound to the isolated protein decreased with increase in pH as monitored by Tb3+ fluorescence. With intact mitochondria the opposite occurred with a large increase in Tb3+ fluorescence at higher pH. This increase was not observed when the mitochondria were preincubated with antimycin  A and rotenone.", "contents": "Binding of fluorescent lanthanides to rat liver mitochondrial membranes and calcium ion-binding proteins. (1) Tb3+ binding to mitochondrial membranes can be monitored by enhanced ion fluorescence at 545 nm with excitation at 285 nm. At low protein concentrations (less than 30 mug/ml) no inner filter effects are observed. (2) This binding is localized at the external surface of the inner membrane and is unaffected by inhibitors of respiration or oxidative phosphorylation. (3) A soluble Ca2+ binding protein isolated according to Lehninger, A.L. ((1971) Biochem. Biophys. Res. Commun. 42, 312-317) also binds Tb3+ with enhanced ion fluorescence upon excitation at 285 nm. The excitation spectrum of the isolated protein and of the intact mitochondria are indicative of an aromatic amino acid at the cation binding site. (4) Further characterization of the Tb3+-protein interaction revealed that there is more than one binding site per protein molecule and that these sites are clustered (less than 20 A). Neuraminidase treatment or organic solvent extraction of the protein did not affect fluorescent Tb3+ binding. (5) pH dependency studies of Tb3+ binding to the isolated protein or intact mitochondria demonstrated the importance of an ionizable group of pK greater than 6. At pH less than 7.5 the amount of Tb3+ bound to the isolated protein decreased with increase in pH as monitored by Tb3+ fluorescence. With intact mitochondria the opposite occurred with a large increase in Tb3+ fluorescence at higher pH. This increase was not observed when the mitochondria were preincubated with antimycin  A and rotenone."}
{"id": "PMID:6062", "title": "A nonspecific inhibitory effect of tRNA on the activity of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Saccharomyces cerevisiae.", "content": "The inhibitory effect of tRNA on yeast 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase (EC 4.1.2.15) has been reinvestigated. From earlier studies the inhibition by tRNAPhe appeared to be quite specific. This study shows that tRNAPhe is indeed a potent inhibitor but so is unfractionated tRNA, as well as ribosomal RNA and heparin. Complete digestion to mononucleotides relieves the inhibition. Since the enzyme requires a metal ion (Co2+) we suggest that the RNA and heparin are inhibitory by virtue of their capacity to chelate the Co2+.", "contents": "A nonspecific inhibitory effect of tRNA on the activity of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Saccharomyces cerevisiae. The inhibitory effect of tRNA on yeast 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase (EC 4.1.2.15) has been reinvestigated. From earlier studies the inhibition by tRNAPhe appeared to be quite specific. This study shows that tRNAPhe is indeed a potent inhibitor but so is unfractionated tRNA, as well as ribosomal RNA and heparin. Complete digestion to mononucleotides relieves the inhibition. Since the enzyme requires a metal ion (Co2+) we suggest that the RNA and heparin are inhibitory by virtue of their capacity to chelate the Co2+."}
{"id": "PMID:6063", "title": "Effects of increased intracellular pH-buffering capacity on the light response of Limulus ventral photoreceptor.", "content": "Aspects of a possible involvement of hydrogen ions in the electrophysiological responses to light of Limulus ventral photoreceptors were investigated. A 1 M solution of either a zwitter-ionic pH buffer or a weakly-buffering control substance was pressure injected through a micropipette into a ventral photoreceptor cell. To estimate the amount injected, 35SO4 was included in the solution. Membrane currents induced by light flashes were measured by a voltage-clamp technique. The buffer-filled micropipette passed current and a 3M KCl filled micropipette monitored membrane voltage. The sensitivity (peak light-induced current/stimulus energy) was measured, after dark adaptation, before and after injection. Injections of buffers, pH 6.3-7.2, to intracellular concentrations of at least 40-200 mM produced only a small mean decrease in sensitivity, approximately equal to that caused by injections of control substances. Excitation, therefore, apparently is not mediated by a change in intracellular pH. Buffers with pH values 5.4-8.4 were also injected. The time to peak of the response depended on pH, being shortened by up to 20% at pH values below 7.7 and lengthened at higher pH values. The time to peak of the response appeared to be shortened by an increase in intracellular pH-buffering capacity even when there was no change in intracellular pH.", "contents": "Effects of increased intracellular pH-buffering capacity on the light response of Limulus ventral photoreceptor. Aspects of a possible involvement of hydrogen ions in the electrophysiological responses to light of Limulus ventral photoreceptors were investigated. A 1 M solution of either a zwitter-ionic pH buffer or a weakly-buffering control substance was pressure injected through a micropipette into a ventral photoreceptor cell. To estimate the amount injected, 35SO4 was included in the solution. Membrane currents induced by light flashes were measured by a voltage-clamp technique. The buffer-filled micropipette passed current and a 3M KCl filled micropipette monitored membrane voltage. The sensitivity (peak light-induced current/stimulus energy) was measured, after dark adaptation, before and after injection. Injections of buffers, pH 6.3-7.2, to intracellular concentrations of at least 40-200 mM produced only a small mean decrease in sensitivity, approximately equal to that caused by injections of control substances. Excitation, therefore, apparently is not mediated by a change in intracellular pH. Buffers with pH values 5.4-8.4 were also injected. The time to peak of the response depended on pH, being shortened by up to 20% at pH values below 7.7 and lengthened at higher pH values. The time to peak of the response appeared to be shortened by an increase in intracellular pH-buffering capacity even when there was no change in intracellular pH."}
{"id": "PMID:6065", "title": "Lipid-protein interactions in membrane models. Fluorescence polarization study of cytochrome b5-phospholipids complexes.", "content": "According to previous authors, cytochrome b5, when extracted from bovine liver by a detergent method, is called cytochrome d-b5. On the other hand, the protein obtained after trypsin action, which eliminates an hydrophobic peptide of about 54 residues, is called cytochrome t-b5. Fluorescence polarization of the dansyl phosphatidylethanolamine probe inserted into phospholipid vesicles is very sensitive to the binding of proteins, and so is a useful method to study lipid-protein interactions. The chromophore mobility, R, decreases markedly when dipalmitoyl phosphatidylcholine vesicles are incubated with cytochrome d-b5, whereas R does not change for cytochrome c and cytochrome t-b5. This can be interpreted as a strengthening of bilayer, only due to the interaction of the hydrophobic peptide tail. Interaction of dipalmitoly phosphatidylcholine vesicles with cytochrome d-b5 occurs either below or above the melting temperature of the aliphatic chains (41 degrees C). Even for a high protein to lipid molar ratio (1 molecule of protein for 40 phospholipid molecules), the melting temperature is apparently unaffected. Phosphatidylserine and phosphatidylinositol do not interact at pH 7.7 with cytochrome d-b5, because electrostatic forces prevent formation of complexes. At low pH, the interaction with the protein occurs, but the binding is mainly of electrostatic nature.", "contents": "Lipid-protein interactions in membrane models. Fluorescence polarization study of cytochrome b5-phospholipids complexes. According to previous authors, cytochrome b5, when extracted from bovine liver by a detergent method, is called cytochrome d-b5. On the other hand, the protein obtained after trypsin action, which eliminates an hydrophobic peptide of about 54 residues, is called cytochrome t-b5. Fluorescence polarization of the dansyl phosphatidylethanolamine probe inserted into phospholipid vesicles is very sensitive to the binding of proteins, and so is a useful method to study lipid-protein interactions. The chromophore mobility, R, decreases markedly when dipalmitoyl phosphatidylcholine vesicles are incubated with cytochrome d-b5, whereas R does not change for cytochrome c and cytochrome t-b5. This can be interpreted as a strengthening of bilayer, only due to the interaction of the hydrophobic peptide tail. Interaction of dipalmitoly phosphatidylcholine vesicles with cytochrome d-b5 occurs either below or above the melting temperature of the aliphatic chains (41 degrees C). Even for a high protein to lipid molar ratio (1 molecule of protein for 40 phospholipid molecules), the melting temperature is apparently unaffected. Phosphatidylserine and phosphatidylinositol do not interact at pH 7.7 with cytochrome d-b5, because electrostatic forces prevent formation of complexes. At low pH, the interaction with the protein occurs, but the binding is mainly of electrostatic nature."}
{"id": "PMID:6066", "title": "Phosphatidic acid phosphatase and phospholipdase A activities in plasma membranes from fusing muscle cells.", "content": "Plasma membrane from fusing embryonic muscle cells were assayed for phospholipase A activity to determine if this enzyme plays a role in cell fusion. The membranes were assayed under a variety of conditions with phosphatidylcholine as the substrate and no phospholipase A activity was found. The plasma membranes did contain a phosphatidic acid phosphatase which was optimally active in the presence of Triton X-100 and glycerol. The enzyme activity was constant from pH 5.2 to 7.0, and did not require divalent cations. Over 97% of the phosphatidic acid phosphatase activity was in the particulate fraction. The subcellular distribution of the phosphatidic acid phosphatase was the same as the distributions of the plasma membrane markers, (Na+ + k+)-ATPase and the acetylcholine receptor, which indicates that this phosphatase is located exclusively in the plasma membranes. There was no detectable difference in the phosphatidic acid phosphatase activities of plasma membranes from fusing and non-fusing cells.", "contents": "Phosphatidic acid phosphatase and phospholipdase A activities in plasma membranes from fusing muscle cells. Plasma membrane from fusing embryonic muscle cells were assayed for phospholipase A activity to determine if this enzyme plays a role in cell fusion. The membranes were assayed under a variety of conditions with phosphatidylcholine as the substrate and no phospholipase A activity was found. The plasma membranes did contain a phosphatidic acid phosphatase which was optimally active in the presence of Triton X-100 and glycerol. The enzyme activity was constant from pH 5.2 to 7.0, and did not require divalent cations. Over 97% of the phosphatidic acid phosphatase activity was in the particulate fraction. The subcellular distribution of the phosphatidic acid phosphatase was the same as the distributions of the plasma membrane markers, (Na+ + k+)-ATPase and the acetylcholine receptor, which indicates that this phosphatase is located exclusively in the plasma membranes. There was no detectable difference in the phosphatidic acid phosphatase activities of plasma membranes from fusing and non-fusing cells."}
{"id": "PMID:6067", "title": "Amino acid stimulation of ATP cleavage by two Ehrlich cell membrane preparations in the presence of ouabain.", "content": "Two membrane fractions prepared from the Ehrlich ascites-tumor cell show non-identical stimulatory responses to certain amino acids in their Mg+2 -dependent activity to cleave ATP, despite the presence of ouabain and the absence of Na+ or K+. The first of these, previously described, shows little (Na+ + K+)-ATPase activity, and is characteristicallly stimulated by the presence of certain diamino acids with low pK2, and at pH values suggesting that the cationic forms of these amino acids are effective. The evidence indicates that these effects are not obtained through occupation of the kinetically discernible receptor site serving characteristically for the uphill transport of these amino acids into the Ehrlich cell. The second membrane preparation was purified with the goal of concentrating the (Na+ +K+)-ATPase activity. It also is stimulated by the model diamino acid, 4-amino-1-methylpiperidine-4-carboxylic acid, and several ordinary amino acids. The diamino acids were most effective at pH values where the neutral zwitterionic forms might be responsible. Among the optically active amino acids tested, the effects of ornithine and leucine were substantially stronger for the L than for the D isomers. The list of stimulatory amino acids again corresponds poorly to any single transport system, although the possibility was not excluded that stimulation might occur for both preparations by occupation of a membrane site which ordinarily is kinetically silent in the transport sequence. The high sensitivity to deoxycholate and to dicyclohexylcarbodiimide of the hydrolytic activity produced by the presence of L-ornithine and 4-amino-1-methyl-piperidine-4-carboxylic acid suggests that the stimulatory effect is not merely a general intensification of the background Mg+ -dependent hydrolytic activity.", "contents": "Amino acid stimulation of ATP cleavage by two Ehrlich cell membrane preparations in the presence of ouabain. Two membrane fractions prepared from the Ehrlich ascites-tumor cell show non-identical stimulatory responses to certain amino acids in their Mg+2 -dependent activity to cleave ATP, despite the presence of ouabain and the absence of Na+ or K+. The first of these, previously described, shows little (Na+ + K+)-ATPase activity, and is characteristicallly stimulated by the presence of certain diamino acids with low pK2, and at pH values suggesting that the cationic forms of these amino acids are effective. The evidence indicates that these effects are not obtained through occupation of the kinetically discernible receptor site serving characteristically for the uphill transport of these amino acids into the Ehrlich cell. The second membrane preparation was purified with the goal of concentrating the (Na+ +K+)-ATPase activity. It also is stimulated by the model diamino acid, 4-amino-1-methylpiperidine-4-carboxylic acid, and several ordinary amino acids. The diamino acids were most effective at pH values where the neutral zwitterionic forms might be responsible. Among the optically active amino acids tested, the effects of ornithine and leucine were substantially stronger for the L than for the D isomers. The list of stimulatory amino acids again corresponds poorly to any single transport system, although the possibility was not excluded that stimulation might occur for both preparations by occupation of a membrane site which ordinarily is kinetically silent in the transport sequence. The high sensitivity to deoxycholate and to dicyclohexylcarbodiimide of the hydrolytic activity produced by the presence of L-ornithine and 4-amino-1-methyl-piperidine-4-carboxylic acid suggests that the stimulatory effect is not merely a general intensification of the background Mg+ -dependent hydrolytic activity."}
{"id": "PMID:6068", "title": "[Partial purification and study of gamma-glutamyl transpeptidase from sheep cerebral capillaries].", "content": "Gamma-glutamyl transpeptidase was purified 53 times from Sheep brain cortex capillaries. On gel filtration it appears homogeneous with a M.W. = 350 000. The enzyme is likely a glycoprotein, the properties of which are close to hog kidney gamma-glutamyl transpeptidase ; gamma-glutamyl aminoacid formation is assayed electrophoretically. The results obtained using several aminoacids are in favour of the existence of different units, specific of each group of aminoacids ; together with the data from structural analogs, they support the hypothesis that gamma-glutamyl transpeptidase participates in aminoacid transport accross blood brain barrier.", "contents": "[Partial purification and study of gamma-glutamyl transpeptidase from sheep cerebral capillaries]. Gamma-glutamyl transpeptidase was purified 53 times from Sheep brain cortex capillaries. On gel filtration it appears homogeneous with a M.W. = 350 000. The enzyme is likely a glycoprotein, the properties of which are close to hog kidney gamma-glutamyl transpeptidase ; gamma-glutamyl aminoacid formation is assayed electrophoretically. The results obtained using several aminoacids are in favour of the existence of different units, specific of each group of aminoacids ; together with the data from structural analogs, they support the hypothesis that gamma-glutamyl transpeptidase participates in aminoacid transport accross blood brain barrier."}
{"id": "PMID:6069", "title": "[Biosynthesis of fatty acids in mouse brain mitochondria in the presence of malonyl-CoA or acetyl-CoA].", "content": "Incorporation of malonyl-CoA or acetyl-CoA is studied in mouse brain mitochondrial fatty acids. Rupture of mitochondria is necessary ; Triton X-100 gives the best result. Other detergents or sonication are of lesser efficiency. Cofactor requirements have been studied : NADH and NADPH have been tested ; ATP increases biosynthesis and CoA causes an inhibition. Two systems of biosynthesis are involved : -- One is a de novo system using malonyl-CoA. Malonyl-CoA alone is incorporated and synthesizes mainly C16, indicating the existence of a malonly-CoA decarboxylase although elongation of short chain fatty acids cannot be excluded. Addition of acetyl-CoA increases the biosynthesis and palmityl-CoA when added causes an inhibition. -- The other system, using acetyl-CoA, elongates exogenous palmityl-CoA ; endogenous acyl-CoAs are not elongated by acetyl-CoA. All these results are confirmed by radiogas chromatographic studies of the reactions products.", "contents": "[Biosynthesis of fatty acids in mouse brain mitochondria in the presence of malonyl-CoA or acetyl-CoA]. Incorporation of malonyl-CoA or acetyl-CoA is studied in mouse brain mitochondrial fatty acids. Rupture of mitochondria is necessary ; Triton X-100 gives the best result. Other detergents or sonication are of lesser efficiency. Cofactor requirements have been studied : NADH and NADPH have been tested ; ATP increases biosynthesis and CoA causes an inhibition. Two systems of biosynthesis are involved : -- One is a de novo system using malonyl-CoA. Malonyl-CoA alone is incorporated and synthesizes mainly C16, indicating the existence of a malonly-CoA decarboxylase although elongation of short chain fatty acids cannot be excluded. Addition of acetyl-CoA increases the biosynthesis and palmityl-CoA when added causes an inhibition. -- The other system, using acetyl-CoA, elongates exogenous palmityl-CoA ; endogenous acyl-CoAs are not elongated by acetyl-CoA. All these results are confirmed by radiogas chromatographic studies of the reactions products."}
{"id": "PMID:6070", "title": "[Relationship between the magnitude of Km and pH for L-asparaginase].", "content": "The dependency of L-asparagine hydrolysis rate on L-asparagine concentration in the presence of L-asparaginases from E. coli and Erw. carotovora is studied in a broad pH range. Km values are calculated from the data obtained. It is found that Km insignificantly depends on pH value with the pH range of 5-9 for both asparaginases. Sharp Km maximum is observed at pH greater than 9 in both cases. The maximum position does not coinside with enzyme isoelectric points and with the region of the substrate transition from zwitterionic form into anionic one.", "contents": "[Relationship between the magnitude of Km and pH for L-asparaginase]. The dependency of L-asparagine hydrolysis rate on L-asparagine concentration in the presence of L-asparaginases from E. coli and Erw. carotovora is studied in a broad pH range. Km values are calculated from the data obtained. It is found that Km insignificantly depends on pH value with the pH range of 5-9 for both asparaginases. Sharp Km maximum is observed at pH greater than 9 in both cases. The maximum position does not coinside with enzyme isoelectric points and with the region of the substrate transition from zwitterionic form into anionic one."}
{"id": "PMID:6071", "title": "[Comparative study of endogenous RNA-polymerase activity of the cell nuclei and chloroplasts of pea leaves].", "content": "The endogenous RNApolymerase activity of isolated cell nuclei and chloroplasts from young pea plants (Pisum sativum) has been studied. The presence of all four nucleoside triphosphates and Mg2+ ions is necessary for the reaction. The missing of one of these nucleotides from the reaction mixture, especially ATP, sharply decreases the transcription. Chloroplasts synthesize RNA per DNA unit more intensively, than nuclei. In spring such predominance is especially pronounced. Maximal synthesis of RNA is observed at pH 8.3 both in nuclei and chloroplasts. Maximal transcription was observed at 25 degrees in chloroplasts and at 30--35 degrees in nuclei. Actinomycin D inhibited the process of transcription both in nuclei and some stimulation in chloroplasts were observed, when rifamicin B was added. It is suggested that there are differences in nuclear and chloroplast forms of RNA polymerase.", "contents": "[Comparative study of endogenous RNA-polymerase activity of the cell nuclei and chloroplasts of pea leaves]. The endogenous RNApolymerase activity of isolated cell nuclei and chloroplasts from young pea plants (Pisum sativum) has been studied. The presence of all four nucleoside triphosphates and Mg2+ ions is necessary for the reaction. The missing of one of these nucleotides from the reaction mixture, especially ATP, sharply decreases the transcription. Chloroplasts synthesize RNA per DNA unit more intensively, than nuclei. In spring such predominance is especially pronounced. Maximal synthesis of RNA is observed at pH 8.3 both in nuclei and chloroplasts. Maximal transcription was observed at 25 degrees in chloroplasts and at 30--35 degrees in nuclei. Actinomycin D inhibited the process of transcription both in nuclei and some stimulation in chloroplasts were observed, when rifamicin B was added. It is suggested that there are differences in nuclear and chloroplast forms of RNA polymerase."}
{"id": "PMID:6072", "title": "[Regulation of fodder yeast Candida tropicalis glutamine synthetase activity by the end products of glutamine metabolism].", "content": "Effect of different products of glutamine metabolism on the activity of glutamine synthetase in the presence of Mg2+, and Mn2+ and Co2+ as cofactors is studied. All the metabolites studied are found to inhibit the glutamine synthetase activity in the presence of any cation listed. The degree and the character of the inhibition by one or other metabolite depended in a considerable degree on the nature of the cation presented in the reaction mixture (Mg2+, Mn2+ or Co2+). The mechanism of the cumulative effect of retroinhibitors under the change of Mg2+ or Mn2+ in the reaction mixture was the same.", "contents": "[Regulation of fodder yeast Candida tropicalis glutamine synthetase activity by the end products of glutamine metabolism]. Effect of different products of glutamine metabolism on the activity of glutamine synthetase in the presence of Mg2+, and Mn2+ and Co2+ as cofactors is studied. All the metabolites studied are found to inhibit the glutamine synthetase activity in the presence of any cation listed. The degree and the character of the inhibition by one or other metabolite depended in a considerable degree on the nature of the cation presented in the reaction mixture (Mg2+, Mn2+ or Co2+). The mechanism of the cumulative effect of retroinhibitors under the change of Mg2+ or Mn2+ in the reaction mixture was the same."}
{"id": "PMID:6073", "title": "[Carbonic anhydrase of blue-green alga Spirulina platensis].", "content": "Carboanhydrase (carbonate-hydroliase EC 4.2.1.1.) is found in the extract of Spirulina platensis cells. A linear dependency of the enzyme activity on the protein concentration; pH optimum is found to be 8.0. Specific activity of carboanhydrase is 3 muM/min-mg of protein under the concentration of CO2 of 4-10(-3) M, appearing Michelis constant being 4.9-10(-3) M. The enzyme was stabilized with 10 mM of cisteine, its activity was inhibited by 50% with sulphanylamide (1-10(-5) M), acetazolamide (8--10(-7) M) and Cl- ions (5-10(-2) M). The activity of carboanhydrase, as well as the rate of NaH14CO3 fixation, depended on the pH value of cultural medium.", "contents": "[Carbonic anhydrase of blue-green alga Spirulina platensis]. Carboanhydrase (carbonate-hydroliase EC 4.2.1.1.) is found in the extract of Spirulina platensis cells. A linear dependency of the enzyme activity on the protein concentration; pH optimum is found to be 8.0. Specific activity of carboanhydrase is 3 muM/min-mg of protein under the concentration of CO2 of 4-10(-3) M, appearing Michelis constant being 4.9-10(-3) M. The enzyme was stabilized with 10 mM of cisteine, its activity was inhibited by 50% with sulphanylamide (1-10(-5) M), acetazolamide (8--10(-7) M) and Cl- ions (5-10(-2) M). The activity of carboanhydrase, as well as the rate of NaH14CO3 fixation, depended on the pH value of cultural medium."}
{"id": "PMID:6074", "title": "[Isolation of mitochondrial DNA, purified of nuclear DNA, from animal tissues (degree of methylation and level of pyrimidine nucleotide clustering--criteria of purity)].", "content": "A method of preparation of mitochondria free of nuclear DNA and its fragments by treatment of mitochondria with DEAE-cellulose has been developed. This method is based on binding nuclear nucleic acids and nucleoproteins to DEAE-cellulose particles in the media used for isolation of mitochondria. Treatment with DEAE-cellulose under the conditions described does not induce any visible degradation of mitochondria and mitochondrial DNA. The mitochondrial DNA preparations obtained from beef and rat liver are represented with closed circular molecules of contour length about 5.5 mu. The 5-methylcytosine content in beef and rat mitochondrial DNA (3.03 and 2.0 mole %, respectively) is twice as much as in corresponding nuclear DNA. Besides, mitochondrial DNA strongly differs from nuclear ones by a lower degree of pyrimidine clustering: the amount of mono- and dipyrimidine fragments (about 32 mole %) in mitochondrial DNA is 1.5 times as large and the content of long pyrimidine clusters (hexa- and others) is 2--4 times as low as those in nuclear DNA. The methylation level and the pyrimidine clustering degree may be used as criteria for the purity of mitochondrial DNA from nuclear DNA.", "contents": "[Isolation of mitochondrial DNA, purified of nuclear DNA, from animal tissues (degree of methylation and level of pyrimidine nucleotide clustering--criteria of purity)]. A method of preparation of mitochondria free of nuclear DNA and its fragments by treatment of mitochondria with DEAE-cellulose has been developed. This method is based on binding nuclear nucleic acids and nucleoproteins to DEAE-cellulose particles in the media used for isolation of mitochondria. Treatment with DEAE-cellulose under the conditions described does not induce any visible degradation of mitochondria and mitochondrial DNA. The mitochondrial DNA preparations obtained from beef and rat liver are represented with closed circular molecules of contour length about 5.5 mu. The 5-methylcytosine content in beef and rat mitochondrial DNA (3.03 and 2.0 mole %, respectively) is twice as much as in corresponding nuclear DNA. Besides, mitochondrial DNA strongly differs from nuclear ones by a lower degree of pyrimidine clustering: the amount of mono- and dipyrimidine fragments (about 32 mole %) in mitochondrial DNA is 1.5 times as large and the content of long pyrimidine clusters (hexa- and others) is 2--4 times as low as those in nuclear DNA. The methylation level and the pyrimidine clustering degree may be used as criteria for the purity of mitochondrial DNA from nuclear DNA."}
{"id": "PMID:6076", "title": "[Study of the structure of the histidine decarboxylase of Micrococcus sp. n. by the method of circular dichroism].", "content": "Ring dichroism spectra (RD) of histidine decarboxylase (HDC) from Micrococcus sp. n. at the regions of peptide bonds (200-240 nm) and aromatic amino acids (250-300 nm) absorption are studied. The treatment of RD spectra according to methods of Greenfield-Fasman, Saksena-Vetlaufer and Mayer permits to conclude that at the pH range within 4-8 the content of ordered structures of alpha-helix type comprises 20%, that of beta-structure type-40%, while the rest 40% are represented with polypeptide chain in a disordered globular state. When pH is varied from 1 to 12, the content of alpha-helices decreases from 17 to 5%. There are two distinct dichroic bands in the spectrum of aromatic chromophores absorption (at 270 and 290 nm), the former containing tirosine, tryptophane and phenylalanine residues and the latter being induced with triptophane residues. The study of HDC RD spectra at the regions of peptide bonds and aromatic acids absorption at different temperatures has shown that a part of triptophane, tyrosine and phenylalanine residues is in an ordered structure of the alpha-helix type. The HDC undergoes irreversible changes under heating to 70 degrees and in 8 M urea. 5 M guanidine chloride eliminates the ordered HDC structure, while sodium dodecylsulphate at concentrations up to 1% does not affect the enzyme structure.", "contents": "[Study of the structure of the histidine decarboxylase of Micrococcus sp. n. by the method of circular dichroism]. Ring dichroism spectra (RD) of histidine decarboxylase (HDC) from Micrococcus sp. n. at the regions of peptide bonds (200-240 nm) and aromatic amino acids (250-300 nm) absorption are studied. The treatment of RD spectra according to methods of Greenfield-Fasman, Saksena-Vetlaufer and Mayer permits to conclude that at the pH range within 4-8 the content of ordered structures of alpha-helix type comprises 20%, that of beta-structure type-40%, while the rest 40% are represented with polypeptide chain in a disordered globular state. When pH is varied from 1 to 12, the content of alpha-helices decreases from 17 to 5%. There are two distinct dichroic bands in the spectrum of aromatic chromophores absorption (at 270 and 290 nm), the former containing tirosine, tryptophane and phenylalanine residues and the latter being induced with triptophane residues. The study of HDC RD spectra at the regions of peptide bonds and aromatic acids absorption at different temperatures has shown that a part of triptophane, tyrosine and phenylalanine residues is in an ordered structure of the alpha-helix type. The HDC undergoes irreversible changes under heating to 70 degrees and in 8 M urea. 5 M guanidine chloride eliminates the ordered HDC structure, while sodium dodecylsulphate at concentrations up to 1% does not affect the enzyme structure."}
{"id": "PMID:6077", "title": "[Isolation and several properties of Streptomyces griseus carboxypeptidase].", "content": "Enzymatic and physico-chemical properties of homogenous preparation of carboxypeptidase from Streptomyces griseus are studied. pH-Optimum is found to be 7.9 and 8.2 under the hydrolysis of cbs-Gly-Leu and hyppuryl-arg respectively, temperature optimum --60 degrees C. The enzyme splits more efficiently basic amino acids and leucine from N-terminal-protected dipeptides. Str. griseus carboxypeptidase is activated by reducting agents (NaCN, cisteine, ascorbic acid), it is inhibited by KMnO4 and it does not belong to \"serine\" type enzymes. SH-groups are essential for the enzyme activity. No significant effect of metal ions on the enzyme activity is observed. The inhibitory effect of EDTA developed only after the prolonged treatment. The enzyme has one N-terminal group (alanine), which evidences the presence of one polypeptide chain in the enzyme molecule.", "contents": "[Isolation and several properties of Streptomyces griseus carboxypeptidase]. Enzymatic and physico-chemical properties of homogenous preparation of carboxypeptidase from Streptomyces griseus are studied. pH-Optimum is found to be 7.9 and 8.2 under the hydrolysis of cbs-Gly-Leu and hyppuryl-arg respectively, temperature optimum --60 degrees C. The enzyme splits more efficiently basic amino acids and leucine from N-terminal-protected dipeptides. Str. griseus carboxypeptidase is activated by reducting agents (NaCN, cisteine, ascorbic acid), it is inhibited by KMnO4 and it does not belong to \"serine\" type enzymes. SH-groups are essential for the enzyme activity. No significant effect of metal ions on the enzyme activity is observed. The inhibitory effect of EDTA developed only after the prolonged treatment. The enzyme has one N-terminal group (alanine), which evidences the presence of one polypeptide chain in the enzyme molecule."}
{"id": "PMID:6078", "title": "[Soluble, nuclear and mitochondrial forms of dehydrogenases, pentose-phosphate pathway transferases and nucleases in chicken liver].", "content": "The sub-cellular topography of oxidative and non-oxidative enzymes of the pentose phosphate pathway of carbohydrates metabolism and enzymes of the nucleic exchange (acid and alkaline deoxyribonucleases and ribonucleases) in chicken liver is studied. Nuclear and mitochondrial forms of the enzymes are discovered. The activity of the enzymes studied of carbohydrates metabolism is shown to correlate with that of the enzymes of nucleic metabolism in cytosol, nucleic and mitochondrial liver fractions.", "contents": "[Soluble, nuclear and mitochondrial forms of dehydrogenases, pentose-phosphate pathway transferases and nucleases in chicken liver]. The sub-cellular topography of oxidative and non-oxidative enzymes of the pentose phosphate pathway of carbohydrates metabolism and enzymes of the nucleic exchange (acid and alkaline deoxyribonucleases and ribonucleases) in chicken liver is studied. Nuclear and mitochondrial forms of the enzymes are discovered. The activity of the enzymes studied of carbohydrates metabolism is shown to correlate with that of the enzymes of nucleic metabolism in cytosol, nucleic and mitochondrial liver fractions."}
{"id": "PMID:6079", "title": "[Purification and properties of the riboflavin kinase of the yeast Pichia guilliermondii].", "content": "Riboflavin kinase (E.C.2.7.1.26) was isolated from the cells of the yeast Pichia guilliermondii. The enzyme was 680-fold purified uzing ammonium sulphate fractionation, chromatography on DEAE-Sephadex A-50 and CM-Sephadex C-50 and gel-filtration through Sephadex G-75. Purified enzyme preparation was free from phosphatases and FAD-synthetase. The pH optimum was 8,7, the temperature optimum-45 degrees C. The enzyme was activated by Zn2+, Mg2+ and Co2+ ions. Km for riboflavin was 1,0x10(-5) M, for ATP -- 6,7X10(-6) M. Riboflavin kinase catalyzed the phosphorylation of riboflavin analogues with the substitution of methyl groups at positions 7 and 8. UTP, GTP, ADP and CTP, besides ATP, were phosphate donors. AMP inhibited the enzyme activity. Molecular weight of the enzyme was 28000, as estimated by gel-filtration through Sephadex G-150. Purified riboflavin kinase was stable under storage.", "contents": "[Purification and properties of the riboflavin kinase of the yeast Pichia guilliermondii]. Riboflavin kinase (E.C.2.7.1.26) was isolated from the cells of the yeast Pichia guilliermondii. The enzyme was 680-fold purified uzing ammonium sulphate fractionation, chromatography on DEAE-Sephadex A-50 and CM-Sephadex C-50 and gel-filtration through Sephadex G-75. Purified enzyme preparation was free from phosphatases and FAD-synthetase. The pH optimum was 8,7, the temperature optimum-45 degrees C. The enzyme was activated by Zn2+, Mg2+ and Co2+ ions. Km for riboflavin was 1,0x10(-5) M, for ATP -- 6,7X10(-6) M. Riboflavin kinase catalyzed the phosphorylation of riboflavin analogues with the substitution of methyl groups at positions 7 and 8. UTP, GTP, ADP and CTP, besides ATP, were phosphate donors. AMP inhibited the enzyme activity. Molecular weight of the enzyme was 28000, as estimated by gel-filtration through Sephadex G-150. Purified riboflavin kinase was stable under storage."}
{"id": "PMID:6080", "title": "[Catalytic properties of alpha-ketoglutarate decarboxylase from bovine brain].", "content": "Investigation of the effect of different buffer systems on the rate of alpha-ketoglutarate decarboxylase reaction have shown that the pH optimum is 6.8 in tris-maleic, tris-H3PO4 and KH2PO4-KOH buffers, and it is 7.5 in imidazole buffer. The highest reaction rate was observed when using phosphate containing buffers. The increase of phosphate concentration increased considerably the rate of alpha-ketoglutarate decarboxylase reaction. Mg2+ and Ca2+ were shown to affect slightly the reaction rate. Co2+ and Ag+ slightly inactivated the enzyme. Cu2+ turned to be a very efficient inhibitor of alpha-ketoglutarate decarboxylase reaction. Apparent Mikhaelis constants are determined to be 1.6-10(-3) M for alpha-ketoglutaric acid and 1.7-10(-2)M for 2,6-dichlorphenolindophenol.", "contents": "[Catalytic properties of alpha-ketoglutarate decarboxylase from bovine brain]. Investigation of the effect of different buffer systems on the rate of alpha-ketoglutarate decarboxylase reaction have shown that the pH optimum is 6.8 in tris-maleic, tris-H3PO4 and KH2PO4-KOH buffers, and it is 7.5 in imidazole buffer. The highest reaction rate was observed when using phosphate containing buffers. The increase of phosphate concentration increased considerably the rate of alpha-ketoglutarate decarboxylase reaction. Mg2+ and Ca2+ were shown to affect slightly the reaction rate. Co2+ and Ag+ slightly inactivated the enzyme. Cu2+ turned to be a very efficient inhibitor of alpha-ketoglutarate decarboxylase reaction. Apparent Mikhaelis constants are determined to be 1.6-10(-3) M for alpha-ketoglutaric acid and 1.7-10(-2)M for 2,6-dichlorphenolindophenol."}
{"id": "PMID:6081", "title": "[Immobilized phospholipase D].", "content": "Conditions of phospholipase D adsorption on silica gels have been studied. The immobilized phospholipase D is shown to differ from the soluble form in thermostability, pH optima and activation conditions. A question is discussed as to the connection of the use of activators and the adsorption immobilization. It is assumed that phospholipase D belongs to enzymes, functioning only in the immobilized state.", "contents": "[Immobilized phospholipase D]. Conditions of phospholipase D adsorption on silica gels have been studied. The immobilized phospholipase D is shown to differ from the soluble form in thermostability, pH optima and activation conditions. A question is discussed as to the connection of the use of activators and the adsorption immobilization. It is assumed that phospholipase D belongs to enzymes, functioning only in the immobilized state."}
{"id": "PMID:6086", "title": "Evidence for stem cell function of resting bone marrow lymphocytes identified by the complete 3H-thymidine labelling method.", "content": "Resting bone marrow lymphocytes, recongised as small lymphocytes by light microscopy, were labelled by the complete 3H-thymidine labelling technique, enriched by fractionation on a discontinuous albumin gradient and investigated for their stem cell properties by culture in diffusion chambers. Fraction 3, with the highest enrichment of labelled small lymphocytes and slight enrichment of other labelled cells (reticulum and endothelial cells), produced substantial growth, in contrast to fraction 4, with no enrichment of these cells. The number of labelled small lymphocytes per chamber in fraction 3 remained constant or tended to increase. This is assumed to be an indication of some degree of self-replication in the small lymphocyte population. Since, however, their labelling intensity decreased only slowly, it must be further concluded that part of the labelled small lymphocyte population probably remained resting. Some labelled transitional and blast cells appeared before the development of recognisable myelopoietic and erythropoietic precursors and of megakaryocytes, in agreement with the concept that small lymphocytes transfrom to transitional cells during the developmetn of normal haempopiesis.", "contents": "Evidence for stem cell function of resting bone marrow lymphocytes identified by the complete 3H-thymidine labelling method. Resting bone marrow lymphocytes, recongised as small lymphocytes by light microscopy, were labelled by the complete 3H-thymidine labelling technique, enriched by fractionation on a discontinuous albumin gradient and investigated for their stem cell properties by culture in diffusion chambers. Fraction 3, with the highest enrichment of labelled small lymphocytes and slight enrichment of other labelled cells (reticulum and endothelial cells), produced substantial growth, in contrast to fraction 4, with no enrichment of these cells. The number of labelled small lymphocytes per chamber in fraction 3 remained constant or tended to increase. This is assumed to be an indication of some degree of self-replication in the small lymphocyte population. Since, however, their labelling intensity decreased only slowly, it must be further concluded that part of the labelled small lymphocyte population probably remained resting. Some labelled transitional and blast cells appeared before the development of recognisable myelopoietic and erythropoietic precursors and of megakaryocytes, in agreement with the concept that small lymphocytes transfrom to transitional cells during the developmetn of normal haempopiesis."}
{"id": "PMID:6087", "title": "Changes in the electric dipole vector of human serum albumin due to complexing with fatty acids.", "content": "The magnitude of the electric dipole vector of human serum albumin, as measured by the dielectric increment of the isoionic solution, is found to be a sensitive, monotonic indicator of the number of moles (up to at least 5) of long chain fatty acid complexed. The sensitivity is about three times as great as it is in bovine albumin. New methods of analysis of the frequency dispersion of the dielectric constant were developed to ascertain if molecular shape changes also accompany the complexing with fatty acid. Direct two-component rotary diffusion constant analysis is found to be too strongly affected by cross modulation between small systematic errors and physically significant data components to be a reliable measure of structural modification. Multicomponent relaxation profiles are more useful as recognition patterns for structural comparisons, but the equations involved are ill-conditioned and solutions based on standard least-squares regression contain mathematical artifacts which mask the physically significant spectrum. By constraining the solution to non-negative coefficients, the magnitude of the artifacts is reduced to well below the magnitudes of the spectral components. Profiles calculated in this way show no evidence of significant dipole direction or molecular shape change as the albumin is complexed with 1 mol of fatty acid. In these experiments albumin was defatted by incubation with adipose tissue at physiological pH, which avoids passing the protein through the pH of the N-F transition usually required in defatting. Addition of fatty acid from soluion in small amounts of ethanol appears to form a complex indistinguishable from the \"native\" complex.", "contents": "Changes in the electric dipole vector of human serum albumin due to complexing with fatty acids. The magnitude of the electric dipole vector of human serum albumin, as measured by the dielectric increment of the isoionic solution, is found to be a sensitive, monotonic indicator of the number of moles (up to at least 5) of long chain fatty acid complexed. The sensitivity is about three times as great as it is in bovine albumin. New methods of analysis of the frequency dispersion of the dielectric constant were developed to ascertain if molecular shape changes also accompany the complexing with fatty acid. Direct two-component rotary diffusion constant analysis is found to be too strongly affected by cross modulation between small systematic errors and physically significant data components to be a reliable measure of structural modification. Multicomponent relaxation profiles are more useful as recognition patterns for structural comparisons, but the equations involved are ill-conditioned and solutions based on standard least-squares regression contain mathematical artifacts which mask the physically significant spectrum. By constraining the solution to non-negative coefficients, the magnitude of the artifacts is reduced to well below the magnitudes of the spectral components. Profiles calculated in this way show no evidence of significant dipole direction or molecular shape change as the albumin is complexed with 1 mol of fatty acid. In these experiments albumin was defatted by incubation with adipose tissue at physiological pH, which avoids passing the protein through the pH of the N-F transition usually required in defatting. Addition of fatty acid from soluion in small amounts of ethanol appears to form a complex indistinguishable from the \"native\" complex."}
{"id": "PMID:6089", "title": "[Cloning stem cells in the bone marrow of irradiated mice].", "content": "Different amount of intact or irradiated bone marrow from syngenous donors was administered to mice irradiated with a lethal dose. There was revealed a linear dependence of the number of the 8-9-day colonies grown in the bone marrow of the femur on the amount of the administered cells, and an exponential dependence on the irradiation dose. Regularity of the stem cell cloning in the bone marrow was analogous to such in the spleen. Radiosensitivity of the colony-forming units (CFU) differed depending on the site (the spleen, the bone marrow) of their colony formation. The CFU settling in the marrow proved to be more radioresistant (D(0) equalled 160-200 P) in comparison with the CFU settling in the spleen (D(0) constituted 80-100 P). It is supposed that a different radiosensitivity of the CFU was caused by the presence of heterogenic population of the stem cells and also by specific peculiarities of the organ (the spleen, the bone marrow) in which the colonies formed.", "contents": "[Cloning stem cells in the bone marrow of irradiated mice]. Different amount of intact or irradiated bone marrow from syngenous donors was administered to mice irradiated with a lethal dose. There was revealed a linear dependence of the number of the 8-9-day colonies grown in the bone marrow of the femur on the amount of the administered cells, and an exponential dependence on the irradiation dose. Regularity of the stem cell cloning in the bone marrow was analogous to such in the spleen. Radiosensitivity of the colony-forming units (CFU) differed depending on the site (the spleen, the bone marrow) of their colony formation. The CFU settling in the marrow proved to be more radioresistant (D(0) equalled 160-200 P) in comparison with the CFU settling in the spleen (D(0) constituted 80-100 P). It is supposed that a different radiosensitivity of the CFU was caused by the presence of heterogenic population of the stem cells and also by specific peculiarities of the organ (the spleen, the bone marrow) in which the colonies formed."}
{"id": "PMID:6090", "title": "[The effect of psychotropic substances (aminazin, majeptil, trisedil) on protein synthesis in different regions of the rat brain].", "content": "Experiments were conducted on rats; a study was made of methionineS35 incorporation into the sum total proteins isolated from various portions of the brain after a single administration of chlorpromazine, majeptil and tricedil. A generalized depression of protein synthesis in all the structures, except the medulla oblongata, followed chlorpromazine administration in one and three hours. A stimulating effect is characteristic of majeptil in the majority of the brain portions. The action of tricedil was accompanied by reduction of methionine-S35 incorporation into the proteins of the majority of the brain structures and by an increase in its incorporation into the olfactory lobes. As supposed, changes in the protein synthesis in individual structures of the brain served as an important link in the action mechanism of psychotropic preparations on the organism.", "contents": "[The effect of psychotropic substances (aminazin, majeptil, trisedil) on protein synthesis in different regions of the rat brain]. Experiments were conducted on rats; a study was made of methionineS35 incorporation into the sum total proteins isolated from various portions of the brain after a single administration of chlorpromazine, majeptil and tricedil. A generalized depression of protein synthesis in all the structures, except the medulla oblongata, followed chlorpromazine administration in one and three hours. A stimulating effect is characteristic of majeptil in the majority of the brain portions. The action of tricedil was accompanied by reduction of methionine-S35 incorporation into the proteins of the majority of the brain structures and by an increase in its incorporation into the olfactory lobes. As supposed, changes in the protein synthesis in individual structures of the brain served as an important link in the action mechanism of psychotropic preparations on the organism."}
{"id": "PMID:6091", "title": "[Effect of noradrenaline on the electrical and contractile properties of smooth muscle cells in the pulmonary artery].", "content": "Experiments were performed on the smooth muscle cells of rabbit a. pulmonalis using the microelectrode technique. No spontaneous electrical or mechanical activity was recorded in normal Krebs solution. The current-voltage relation in these smooth muscle cells showed marked rectification. No changes in the isometric tension were observed due to the anodal or cathodal stimulating currents. Strong depolarization of the muscle cells produced only local potentials on the cathelectrotone which never developed into a spike. Noradrenaline (10(-8) g/ml) caused depolarization of the 5-7 mV in the muscle cell membrane and a considerable contraction of the muscle strip as well. Under such conditions the contractile apparatus of the muscle cells became sensible to the resting potential level. Anodal stimulation was accompanied by relaxation of the muscle strip, whereas cathodal stimulation--by its contraction. The alpha-adrenoblocking agent (phentolamine) blocked the effect of noradrenaline evidencing the fact that noradrenaline exerted its excitatory action on the smooth muscle cells of the a. pulmonalis through the alpha-adrenoreceptors.", "contents": "[Effect of noradrenaline on the electrical and contractile properties of smooth muscle cells in the pulmonary artery]. Experiments were performed on the smooth muscle cells of rabbit a. pulmonalis using the microelectrode technique. No spontaneous electrical or mechanical activity was recorded in normal Krebs solution. The current-voltage relation in these smooth muscle cells showed marked rectification. No changes in the isometric tension were observed due to the anodal or cathodal stimulating currents. Strong depolarization of the muscle cells produced only local potentials on the cathelectrotone which never developed into a spike. Noradrenaline (10(-8) g/ml) caused depolarization of the 5-7 mV in the muscle cell membrane and a considerable contraction of the muscle strip as well. Under such conditions the contractile apparatus of the muscle cells became sensible to the resting potential level. Anodal stimulation was accompanied by relaxation of the muscle strip, whereas cathodal stimulation--by its contraction. The alpha-adrenoblocking agent (phentolamine) blocked the effect of noradrenaline evidencing the fact that noradrenaline exerted its excitatory action on the smooth muscle cells of the a. pulmonalis through the alpha-adrenoreceptors."}
{"id": "PMID:6092", "title": "[Hydroxylation in isolated liver cells].", "content": "Ethylenediamine tetraacetate and mechanical treatment were applied to obtain the isolated hepatocytes. Oxidative phosphorylation was found to be preserved in the isolated cells. Hepatocytes were capable of hydroxylation of dimethylaniline (DMA), ethylmorphine and aminopyrine. VMAX for the hydroxylation of DMA calculated as per 1 nmol of the cytochrome P--450 was higher in the cells than in the microsomes. NADH formed during the oxidation of glutamate and malate can be used for hydroxylation.", "contents": "[Hydroxylation in isolated liver cells]. Ethylenediamine tetraacetate and mechanical treatment were applied to obtain the isolated hepatocytes. Oxidative phosphorylation was found to be preserved in the isolated cells. Hepatocytes were capable of hydroxylation of dimethylaniline (DMA), ethylmorphine and aminopyrine. VMAX for the hydroxylation of DMA calculated as per 1 nmol of the cytochrome P--450 was higher in the cells than in the microsomes. NADH formed during the oxidation of glutamate and malate can be used for hydroxylation."}
{"id": "PMID:6093", "title": "[Effect of carbidine on the content and storage of adrenergic neurotransmitter in the synaptic vesicles].", "content": "The influence of carbidine, an original psychotropic drug, on the adrenergic neurotransmitter content and storage in the sympathetic nerves was studied with the use of cytochemical electron microscopy. The influence of carbidine on the uptake of the exogenous noradrenaline (NA) in the synaptic vesicles was also studied. Carbidine was found to be capable to decreasing the NA storage in the synaptic vesicles and failed to block the accumulation of the exogenous NA in the synaptic vesicles.", "contents": "[Effect of carbidine on the content and storage of adrenergic neurotransmitter in the synaptic vesicles]. The influence of carbidine, an original psychotropic drug, on the adrenergic neurotransmitter content and storage in the sympathetic nerves was studied with the use of cytochemical electron microscopy. The influence of carbidine on the uptake of the exogenous noradrenaline (NA) in the synaptic vesicles was also studied. Carbidine was found to be capable to decreasing the NA storage in the synaptic vesicles and failed to block the accumulation of the exogenous NA in the synaptic vesicles."}
{"id": "PMID:6094", "title": "[Activity of NAD- and NADP-dependent malate dehydrogenase isoenzymes in the myocardium of rabbits with alloxan diabetes].", "content": "Isoenzymes NAD-and NaDP MDH were detected in the cardiac muscle of rabbits by disc electrophoresis in polyacrylamide gel. Alloxan diabetes proved to be accompanied by a significant reduction in the activity of mitochondrial NADP MDH (in the reaction of malic decarboxylation) and its increase in cytozol. The activity of NAD-MDH (in the reaction of oxyacetate reduction) was also decreased in various isoenzymes in the myocardium (particularly in the mitochondria) in diabetes. Insulin restored the correlation of the activities of the isoenzymes NAD- and NADP-MDH in the cytostructures of the myocardium disturbed in diabetes.", "contents": "[Activity of NAD- and NADP-dependent malate dehydrogenase isoenzymes in the myocardium of rabbits with alloxan diabetes]. Isoenzymes NAD-and NaDP MDH were detected in the cardiac muscle of rabbits by disc electrophoresis in polyacrylamide gel. Alloxan diabetes proved to be accompanied by a significant reduction in the activity of mitochondrial NADP MDH (in the reaction of malic decarboxylation) and its increase in cytozol. The activity of NAD-MDH (in the reaction of oxyacetate reduction) was also decreased in various isoenzymes in the myocardium (particularly in the mitochondria) in diabetes. Insulin restored the correlation of the activities of the isoenzymes NAD- and NADP-MDH in the cytostructures of the myocardium disturbed in diabetes."}
{"id": "PMID:6095", "title": "[Cyproheptadine as an inhibitor of the effects of bradykinin].", "content": "A study was made of the influence of ciproheptadin, serotonin and histamine inhibitor, on the effects of exo- and endogenous bradykinin. Ciproheptadin inhibited the effect of bradykinin on a section of a guinea pig intestine in vitro, eliminated the hypotensive effect of bradykinin in rats in vivo, and also blocked the constriction of the vessels of the ear in rabbit and a fall of the blood kininogen level caused by the administration of pyrogenal.", "contents": "[Cyproheptadine as an inhibitor of the effects of bradykinin]. A study was made of the influence of ciproheptadin, serotonin and histamine inhibitor, on the effects of exo- and endogenous bradykinin. Ciproheptadin inhibited the effect of bradykinin on a section of a guinea pig intestine in vitro, eliminated the hypotensive effect of bradykinin in rats in vivo, and also blocked the constriction of the vessels of the ear in rabbit and a fall of the blood kininogen level caused by the administration of pyrogenal."}
{"id": "PMID:6096", "title": "[Mg, Ca-activated ATP-ase of Pacinian corpuscles].", "content": "Adenosine triphosphatase (ATPase) activated by Mg2+ or Ca2+ ions was detected in single mechanoreceptors (Pacini's corpuscles) of cat; addition of Ca2+ (10(-5)M) to Mg-ATP-ase increased the activity by the factor of 1.6. The activity optimum of Mg- or Co-ATPase was in the alkaline pH zone. A high substrate specificity of Mg, Ca-ATPase was shown. Parachlorinemercury-benzoate (5muM) considerably reduced the activity of Mg, Ca-ATPase, whereas oubain (10(-5)M) failed to affect it significantly. It is supposed that Mg, Ca-ATPase of Pacini's corpuscles was close to actomyosine -like proteins.", "contents": "[Mg, Ca-activated ATP-ase of Pacinian corpuscles]. Adenosine triphosphatase (ATPase) activated by Mg2+ or Ca2+ ions was detected in single mechanoreceptors (Pacini's corpuscles) of cat; addition of Ca2+ (10(-5)M) to Mg-ATP-ase increased the activity by the factor of 1.6. The activity optimum of Mg- or Co-ATPase was in the alkaline pH zone. A high substrate specificity of Mg, Ca-ATPase was shown. Parachlorinemercury-benzoate (5muM) considerably reduced the activity of Mg, Ca-ATPase, whereas oubain (10(-5)M) failed to affect it significantly. It is supposed that Mg, Ca-ATPase of Pacini's corpuscles was close to actomyosine -like proteins."}
{"id": "PMID:6097", "title": "[Activity of adrenal cytoplasmic dehydrogenase following prolonged ACTH administration].", "content": "The activity of cytoplasmic dehydrogenases of the adrenal cells was examined during the prolonged injections of ACTH to Wistar rats. The indices of specific steroid synthesis function of the glands remained relatively high in the course of the whole experiment. Changes in the rats of corticosterone synthesis and dehydrogenase activities were phasic in character; they included an initial synchronic activation the first  two days with its subsequent decrease (7 days of ACTH injections). The prevalence of activities of NADP-dependent dehydrogenases in combination with reactivation of steroidogenesis was marked during the concluding phase (13 days) of the experiment. A possibility of the adaptive role of selective activation of NADP-dependent enzymes in the maintenance of a high level of hormone biosynthesis under conditions of prolonged ACTH stimulation is discussed.", "contents": "[Activity of adrenal cytoplasmic dehydrogenase following prolonged ACTH administration]. The activity of cytoplasmic dehydrogenases of the adrenal cells was examined during the prolonged injections of ACTH to Wistar rats. The indices of specific steroid synthesis function of the glands remained relatively high in the course of the whole experiment. Changes in the rats of corticosterone synthesis and dehydrogenase activities were phasic in character; they included an initial synchronic activation the first  two days with its subsequent decrease (7 days of ACTH injections). The prevalence of activities of NADP-dependent dehydrogenases in combination with reactivation of steroidogenesis was marked during the concluding phase (13 days) of the experiment. A possibility of the adaptive role of selective activation of NADP-dependent enzymes in the maintenance of a high level of hormone biosynthesis under conditions of prolonged ACTH stimulation is discussed."}
{"id": "PMID:6098", "title": "[Effect of hypercapnia on tyrosine and tryptophan metabolism].", "content": "Experiments were conducted on albino rats; it was revealed that an increase in CO2 content in the inspired air (3.8%) caused disturbances in tyrosine and tryptophane metabolism. The activity of tyrosine-aminotranspherase and of tryptophane-oxygenase proved to increase in the liver; blood serum displayed a reduced concentration of free tyrosine and free total tryptophane, but the level of free tryptophane obtained by dialysis proved to rise. A possible significance of these deviations in endogenous blastomogenesis is discussed.", "contents": "[Effect of hypercapnia on tyrosine and tryptophan metabolism]. Experiments were conducted on albino rats; it was revealed that an increase in CO2 content in the inspired air (3.8%) caused disturbances in tyrosine and tryptophane metabolism. The activity of tyrosine-aminotranspherase and of tryptophane-oxygenase proved to increase in the liver; blood serum displayed a reduced concentration of free tyrosine and free total tryptophane, but the level of free tryptophane obtained by dialysis proved to rise. A possible significance of these deviations in endogenous blastomogenesis is discussed."}
{"id": "PMID:6099", "title": "[Mechanism of the analgesic effect of narcotic analgetics].", "content": "A study was made of the effect of morphine, promedol, phentanyl, pentazacine and psychostimulant d,l-amphetamine on the threshold of pain sensitivity and self-stimulation of the hypothalamus and the septum in rats. Electrical stimulation of the systems of positive reinforcement of the hypothalamus and the septum, and also analgetics increased the threshold of pain sensitivity, whereas d,l-amphetamine failed to influence it. D,l-amphetamine and morphine facilitated, promedol failed to influence, phentanyl decreased and pentazacine completely depressed the hypothalamic self-stimulation. The septal self-stimulation remained unaltered under the effect of morphine, promedol, phentanyl, but was decreased under the effect of pentazacine and increased against the background of d,l-amphetamine. A conclusion was drawn that the analgetic action and that activating the positive emotion were independent effects of the psychotropic agents.", "contents": "[Mechanism of the analgesic effect of narcotic analgetics]. A study was made of the effect of morphine, promedol, phentanyl, pentazacine and psychostimulant d,l-amphetamine on the threshold of pain sensitivity and self-stimulation of the hypothalamus and the septum in rats. Electrical stimulation of the systems of positive reinforcement of the hypothalamus and the septum, and also analgetics increased the threshold of pain sensitivity, whereas d,l-amphetamine failed to influence it. D,l-amphetamine and morphine facilitated, promedol failed to influence, phentanyl decreased and pentazacine completely depressed the hypothalamic self-stimulation. The septal self-stimulation remained unaltered under the effect of morphine, promedol, phentanyl, but was decreased under the effect of pentazacine and increased against the background of d,l-amphetamine. A conclusion was drawn that the analgetic action and that activating the positive emotion were independent effects of the psychotropic agents."}
{"id": "PMID:6100", "title": "[Effect of neuroleptics on tyrosine hydroxylase from rat hypothalamus synaptosomes].", "content": "A study was made of the effect of a number of neuroleptics of various chemical structure of tyrosine-hydroxilase isolated from the synaptosomes of rat hypothalamus. A direct spectrophotometric method of determination of the activity of the enzyme was used; it was based on measurement of the absorbence at 335 nm (at the isobestic point for oxidized forms of a synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydropterine). At the tyrosine concentration of 0.15 muM haloperidol, haloanizon, and fluorophenazin were found to increase, and triperidol, droperidol and carbidin -- to decrease the initial rate of thyrosinehydroxilase reaction. All the neuroleptics under study proved to be capable of eliminating the substrate inhibition of the enzyme occurring with a rise of tyrosine concentration to 0.3 mM. The KM value for tyrosine failed to alter with the action of neuroleptics. The effect of neuroleptics was assumed to be of allosteric nature.", "contents": "[Effect of neuroleptics on tyrosine hydroxylase from rat hypothalamus synaptosomes]. A study was made of the effect of a number of neuroleptics of various chemical structure of tyrosine-hydroxilase isolated from the synaptosomes of rat hypothalamus. A direct spectrophotometric method of determination of the activity of the enzyme was used; it was based on measurement of the absorbence at 335 nm (at the isobestic point for oxidized forms of a synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydropterine). At the tyrosine concentration of 0.15 muM haloperidol, haloanizon, and fluorophenazin were found to increase, and triperidol, droperidol and carbidin -- to decrease the initial rate of thyrosinehydroxilase reaction. All the neuroleptics under study proved to be capable of eliminating the substrate inhibition of the enzyme occurring with a rise of tyrosine concentration to 0.3 mM. The KM value for tyrosine failed to alter with the action of neuroleptics. The effect of neuroleptics was assumed to be of allosteric nature."}
{"id": "PMID:6101", "title": "[Elimination of allogeneic inhibition of hematopoietic stem cells by treatment of the recipient mice with cyclophosphane].", "content": "The experiments demonstrated that pretreatment of lethally irradiated recipient (CBA X C57BL/6) F1hybrid mice with cyclophosphamide (200 mg/kg of body weight) on day before the bone marrow transplantation (4 hours after the irradiation) suppressed the allogeneic inhibition of hematopoietic stem cells to 24% (while the inhibition in the untreated animals was 92.5%). It is suggested that cyclophosphamide acted on the recipient's radioresistant lymphoid cells effecting the allogeneic inhibition of stem cells.", "contents": "[Elimination of allogeneic inhibition of hematopoietic stem cells by treatment of the recipient mice with cyclophosphane]. The experiments demonstrated that pretreatment of lethally irradiated recipient (CBA X C57BL/6) F1hybrid mice with cyclophosphamide (200 mg/kg of body weight) on day before the bone marrow transplantation (4 hours after the irradiation) suppressed the allogeneic inhibition of hematopoietic stem cells to 24% (while the inhibition in the untreated animals was 92.5%). It is suggested that cyclophosphamide acted on the recipient's radioresistant lymphoid cells effecting the allogeneic inhibition of stem cells."}
{"id": "PMID:6102", "title": "[Effect of polyinosinic-polycytidylic acid on the colony-forming ability of hematopoietic stem cells in conditions of allogeneic inhibition].", "content": "It was found that the colony-forming capacity of parental bone marrow transplant (C57BL/6) was partially restored in the (CBA X C57BL/6) hybrid recipient irradiated with 800 rad when poly I -- poly C preparation was injected. The effect of poly I -- poly C injection on the colony formation was equivalent to addition of the thymus cells syngeneic with the marrow. In either case the number of splenic colonies was more than double that in the control. On the other hand, it was found that in a completely syngeneic system the number of splenic colonies was not influenced by the thymus cells and poly I -- poly C preparation. Poly I -- poly C doses ranging from 50 to 100 mug and thymus cell doses ranging from 4-10(6) to 8-10(6) did not increase the efficiency of the colony formation with a stable bone marrow dose transplant.", "contents": "[Effect of polyinosinic-polycytidylic acid on the colony-forming ability of hematopoietic stem cells in conditions of allogeneic inhibition]. It was found that the colony-forming capacity of parental bone marrow transplant (C57BL/6) was partially restored in the (CBA X C57BL/6) hybrid recipient irradiated with 800 rad when poly I -- poly C preparation was injected. The effect of poly I -- poly C injection on the colony formation was equivalent to addition of the thymus cells syngeneic with the marrow. In either case the number of splenic colonies was more than double that in the control. On the other hand, it was found that in a completely syngeneic system the number of splenic colonies was not influenced by the thymus cells and poly I -- poly C preparation. Poly I -- poly C doses ranging from 50 to 100 mug and thymus cell doses ranging from 4-10(6) to 8-10(6) did not increase the efficiency of the colony formation with a stable bone marrow dose transplant."}
{"id": "PMID:6103", "title": "[Proliferation and differentiation of hematopoietic stem cells in hypokinesia].", "content": "Using the method of exogenous cloning in vivo of the hemopoietic stem cells of the bone marrow and spleen in the femur and the spleen of mice it was shown that during hypokinesia the kinetics of the stem cells differed in both organs (the spleen and the bone marrow). Differentiation of transplanted stem cells from different sources was unchanged in the spleen, but stem cells of the bone marrow seeding in the femur changed the character of their differentiation in the direction of increase of the erythopoietic function, whereas stem cells of the spleen failed to alter the direction of differentiation.", "contents": "[Proliferation and differentiation of hematopoietic stem cells in hypokinesia]. Using the method of exogenous cloning in vivo of the hemopoietic stem cells of the bone marrow and spleen in the femur and the spleen of mice it was shown that during hypokinesia the kinetics of the stem cells differed in both organs (the spleen and the bone marrow). Differentiation of transplanted stem cells from different sources was unchanged in the spleen, but stem cells of the bone marrow seeding in the femur changed the character of their differentiation in the direction of increase of the erythopoietic function, whereas stem cells of the spleen failed to alter the direction of differentiation."}
{"id": "PMID:6106", "title": "Torsion of the testis and allied conditions.", "content": "In 15 years at Bristol there have been 293 cases of torsion of the testis, 55 cases of torsion of a testicular appendage and 5 cases of testicular ischaemia due to other causes. The risk of a male developing torsion of the testis or its appendix by the age of 25 is about 1 in 160. Both conditions occurred primarily in adolescents, but among prepubertal boys torsion of an appendage was as common as torsion of a normally descended testis. There was a slight left-sided preponderance in testicular torsion, more marked in torsion of the appendages; the incidence of bilateral torsion was 2-0 and 1-8 per cent respectively. The clinical features and differential diagnosis of the two conditions are compared. Torsion of a testicular appendage is the most commonly misdiagnosed scrotal lesion, the preoperative diagnosis being correct in only 11 per cent of cases compared with 90 per cent for torsion of the testis. Twenty-one cases of recurrent torsion underwent prophylactic bilateral orchidopexy. There were 20 cases of torsion of undescended testes, with a salvage rate of only 20 per cent. The overall testicular survival rate was 55-3 per cent. Viability depends upon the possibility of spontaneous reduction, the preoperative delay after the onset of symptoms, the degree of torsion of the cord and the length of follow-up in doubtful cases. Urgent scrotal exploration is advised in every case of acute testicular pain unless there is overwhelming evidence of epididymoorchitis. Exploration of the opposite side is mandatory in torsion of the testis and advisable in torsion of an appendage.", "contents": "Torsion of the testis and allied conditions. In 15 years at Bristol there have been 293 cases of torsion of the testis, 55 cases of torsion of a testicular appendage and 5 cases of testicular ischaemia due to other causes. The risk of a male developing torsion of the testis or its appendix by the age of 25 is about 1 in 160. Both conditions occurred primarily in adolescents, but among prepubertal boys torsion of an appendage was as common as torsion of a normally descended testis. There was a slight left-sided preponderance in testicular torsion, more marked in torsion of the appendages; the incidence of bilateral torsion was 2-0 and 1-8 per cent respectively. The clinical features and differential diagnosis of the two conditions are compared. Torsion of a testicular appendage is the most commonly misdiagnosed scrotal lesion, the preoperative diagnosis being correct in only 11 per cent of cases compared with 90 per cent for torsion of the testis. Twenty-one cases of recurrent torsion underwent prophylactic bilateral orchidopexy. There were 20 cases of torsion of undescended testes, with a salvage rate of only 20 per cent. The overall testicular survival rate was 55-3 per cent. Viability depends upon the possibility of spontaneous reduction, the preoperative delay after the onset of symptoms, the degree of torsion of the cord and the length of follow-up in doubtful cases. Urgent scrotal exploration is advised in every case of acute testicular pain unless there is overwhelming evidence of epididymoorchitis. Exploration of the opposite side is mandatory in torsion of the testis and advisable in torsion of an appendage."}
{"id": "PMID:6109", "title": "Raynaud's phenomenon as side effect of beta-blockers in hypertension.", "content": "A series of 102 hypertensive patients were assessed for the frequency of symptoms of Raynaud's phenomenon and absent peripheral pulses. Out of 21 patients receiving methyldopa alone only one had cold hands and feet whereas among patients on beta-blockers the incidence was 50%. The frequency of both symptoms and absent pulses was highest in patients taking propranolol compared with those taking atenolol or oxprenolol. Patients without a foot pulse were much more likely to have cold hands. A change from propranolol to oxprenolol in some symptomatic patients resulted in improvement. In two patients the skin temperature fell after an 80-mg dose of propranolol. The mechanism by which beta-blockers induce Raynaud's phenomenon is still not clear.", "contents": "Raynaud's phenomenon as side effect of beta-blockers in hypertension. A series of 102 hypertensive patients were assessed for the frequency of symptoms of Raynaud's phenomenon and absent peripheral pulses. Out of 21 patients receiving methyldopa alone only one had cold hands and feet whereas among patients on beta-blockers the incidence was 50%. The frequency of both symptoms and absent pulses was highest in patients taking propranolol compared with those taking atenolol or oxprenolol. Patients without a foot pulse were much more likely to have cold hands. A change from propranolol to oxprenolol in some symptomatic patients resulted in improvement. In two patients the skin temperature fell after an 80-mg dose of propranolol. The mechanism by which beta-blockers induce Raynaud's phenomenon is still not clear."}
{"id": "PMID:6112", "title": "Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways.", "content": "Selective lesions of the dorsal (B7), median (B8), or lateral (B9) raphe nuclei were made stereotaxically in male rats 4 weeks before sacrifice. The extent of damage to each raphe nucleus was quantified histologically by means of a simplified formaldehyde histochemical method for visualization of serotonin in cryostat sections. A detailed mapping of the distribution of the yellow-fluorescent raphe perikarya provided the basis for quantification. Tryptophan hydroxylase activity was measured in 6 forebrain regions from each animal, and the results were correlated with the per cent damage to each raphe nucleus. Tyrosine hydroxylase was also assayed in 5 of these regions; it was not significantly affected by any of the raphe lesions. Dorsal raphe lesions reduced tryptophan hydroxylase activity in the striatum, thalamus, cortex, and hypothalamus, but not in the septal nuclei or hippocampus. Damage to B8 resulted in decrements in this serotonergic enzyme in the septal nuclei, hippocampus, cortex, and hypothalamus, but not in the striatum or thalamus. Lesions of the scattered B9 cells had no significant effect on enzyme activity in any region examined. These data suggest that the dorsal and median raphe nuclei provide two distinct though perhaps overlapping serotonergic systems innervating different parts of the forebrain: a mesostriatal pathway originating in B7 and a mesolimbic system derived from B8. Behavioral studies on the animals, which are presented in a companion paper, indicated that damage to the median nucleus is responsible for many of the behavioral effects previously reported after combined lesions of both major raphe nuclei.", "contents": "Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways. Selective lesions of the dorsal (B7), median (B8), or lateral (B9) raphe nuclei were made stereotaxically in male rats 4 weeks before sacrifice. The extent of damage to each raphe nucleus was quantified histologically by means of a simplified formaldehyde histochemical method for visualization of serotonin in cryostat sections. A detailed mapping of the distribution of the yellow-fluorescent raphe perikarya provided the basis for quantification. Tryptophan hydroxylase activity was measured in 6 forebrain regions from each animal, and the results were correlated with the per cent damage to each raphe nucleus. Tyrosine hydroxylase was also assayed in 5 of these regions; it was not significantly affected by any of the raphe lesions. Dorsal raphe lesions reduced tryptophan hydroxylase activity in the striatum, thalamus, cortex, and hypothalamus, but not in the septal nuclei or hippocampus. Damage to B8 resulted in decrements in this serotonergic enzyme in the septal nuclei, hippocampus, cortex, and hypothalamus, but not in the striatum or thalamus. Lesions of the scattered B9 cells had no significant effect on enzyme activity in any region examined. These data suggest that the dorsal and median raphe nuclei provide two distinct though perhaps overlapping serotonergic systems innervating different parts of the forebrain: a mesostriatal pathway originating in B7 and a mesolimbic system derived from B8. Behavioral studies on the animals, which are presented in a companion paper, indicated that damage to the median nucleus is responsible for many of the behavioral effects previously reported after combined lesions of both major raphe nuclei."}
{"id": "PMID:6114", "title": "Evidence that the rapid binding of newly accumulated noradrenaline within synaptosomes involves synaptic vesicles.", "content": "When rat brain synaptosomes were incubated with [3H]noradrenaline for 1 min and then exposed to osmotic shock, only about 20% of the newly accumulated [3H]noradrenaline was released. It would appear that most, but possibly not all of the newly accumulated [3H]noradrenaline is rapidly bound to some particulate cytoplasmic constituent within the synaptosome. [3H]Dopamine and [3H]5-hydroxytryptamine were also rapidly bound within synaptosomes but [3H]glycine and [3H]gamma-aminobutyric acid were not. Reserpinization (5 mg/kg, i.p., 24 h before preparation) only slightly reduced the initial rate of [3H]noradrenaline uptake by synaptosomes. However, when reserpinized synaptosomes were osmotically shocked, most of the newly accumulated radioactivity was released; this radioactivity was identified chromatographically as [3H]noradrenaline. On the basis of the findings with reserpinized preparations, it seems likely that (1) the rapid intrasynaptosomal binding involves synaptic vesicles and (2) the neuronal membrane transport system itself may be capable of driving the uptake of noradrenaline by nerve-terminals. The rapid vesicular binding observed may not be essential for the accumulation of the amine by presynaptic terminals during brief exposures.", "contents": "Evidence that the rapid binding of newly accumulated noradrenaline within synaptosomes involves synaptic vesicles. When rat brain synaptosomes were incubated with [3H]noradrenaline for 1 min and then exposed to osmotic shock, only about 20% of the newly accumulated [3H]noradrenaline was released. It would appear that most, but possibly not all of the newly accumulated [3H]noradrenaline is rapidly bound to some particulate cytoplasmic constituent within the synaptosome. [3H]Dopamine and [3H]5-hydroxytryptamine were also rapidly bound within synaptosomes but [3H]glycine and [3H]gamma-aminobutyric acid were not. Reserpinization (5 mg/kg, i.p., 24 h before preparation) only slightly reduced the initial rate of [3H]noradrenaline uptake by synaptosomes. However, when reserpinized synaptosomes were osmotically shocked, most of the newly accumulated radioactivity was released; this radioactivity was identified chromatographically as [3H]noradrenaline. On the basis of the findings with reserpinized preparations, it seems likely that (1) the rapid intrasynaptosomal binding involves synaptic vesicles and (2) the neuronal membrane transport system itself may be capable of driving the uptake of noradrenaline by nerve-terminals. The rapid vesicular binding observed may not be essential for the accumulation of the amine by presynaptic terminals during brief exposures."}
{"id": "PMID:6115", "title": "Time-course variations in tyrosine hydroxylase activity in the rat locus coeruleus after electrolytic destruction of the nuclei raphe dorsalis or raphe centralis.", "content": "Time-course variations in tyrosine hydroxylase activity were measured in the locus coeruleus of the albino rat after electrolytic coagulation of either the nucleus raphe dorsalis or the nucleus raphe centralis. Highly significant increases were measured at 4 days after lesioning of the raphe dorsalis (30.33%) and the raphe centralis (81.55%) compared with control values, whereas the activity in groups A9 and A10 was unchanged at this time-point. In conjunction with other experimental evidences, an hypothesis is proposed that the catecholaminergic neurons located in the locus coeruleus are directly and/or indirectly controlled by the serotonin-containing neurons located in the anterior raphe system nuclei.", "contents": "Time-course variations in tyrosine hydroxylase activity in the rat locus coeruleus after electrolytic destruction of the nuclei raphe dorsalis or raphe centralis. Time-course variations in tyrosine hydroxylase activity were measured in the locus coeruleus of the albino rat after electrolytic coagulation of either the nucleus raphe dorsalis or the nucleus raphe centralis. Highly significant increases were measured at 4 days after lesioning of the raphe dorsalis (30.33%) and the raphe centralis (81.55%) compared with control values, whereas the activity in groups A9 and A10 was unchanged at this time-point. In conjunction with other experimental evidences, an hypothesis is proposed that the catecholaminergic neurons located in the locus coeruleus are directly and/or indirectly controlled by the serotonin-containing neurons located in the anterior raphe system nuclei."}
{"id": "PMID:6119", "title": "Resting and stimulated values of model parameters governing transmitter release at a synapse in Aplysia californica.", "content": "Transmitter release (R) at a synpase in Aplysia californica can be analyzed in terms of a model with the following parameters: A, the available pool of transmitter; F, the fraction of available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; D, the rate constant of demobilization of transmitter from the available pool. In the present paper we show that: (1) beginning with an analysis of the recovery from depression of the second of a pair of disolated EPSPs separated by a series of intervals of about 10-60 sec, and assuming that the recovery is due to refilling of a depleted A, it is possible to estimate resting equilibrium values of these parameters; (2) changes in these parameters when a new equilbrium state is reached after prolonged stimulation (e.g., 300 stimuli at 1/sec) can then be quantitatively determined; (3) the increased rate of transmitter release observed during and after repetitive stimulation is the consequence of increases in F and M with changes in A passively following; and (4) there are significant correlations among certain resting parameters and between the values of certain resting parameters and these parameters upon stimulation. Preparations with a large resting F tend to have a relatively small resting A. Preparations with a large resting F or M tend to increase these less with stimulation than preparations with smaller resting values of these parameters. Preparations with large stimulus-dependent increases in F tend to have large stimulus-dependent increases in M.", "contents": "Resting and stimulated values of model parameters governing transmitter release at a synapse in Aplysia californica. Transmitter release (R) at a synpase in Aplysia californica can be analyzed in terms of a model with the following parameters: A, the available pool of transmitter; F, the fraction of available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; D, the rate constant of demobilization of transmitter from the available pool. In the present paper we show that: (1) beginning with an analysis of the recovery from depression of the second of a pair of disolated EPSPs separated by a series of intervals of about 10-60 sec, and assuming that the recovery is due to refilling of a depleted A, it is possible to estimate resting equilibrium values of these parameters; (2) changes in these parameters when a new equilbrium state is reached after prolonged stimulation (e.g., 300 stimuli at 1/sec) can then be quantitatively determined; (3) the increased rate of transmitter release observed during and after repetitive stimulation is the consequence of increases in F and M with changes in A passively following; and (4) there are significant correlations among certain resting parameters and between the values of certain resting parameters and these parameters upon stimulation. Preparations with a large resting F tend to have a relatively small resting A. Preparations with a large resting F or M tend to increase these less with stimulation than preparations with smaller resting values of these parameters. Preparations with large stimulus-dependent increases in F tend to have large stimulus-dependent increases in M."}
{"id": "PMID:6120", "title": "Synaptic depression at a synapse in Aplysia californica: analysis in terms of a material flow model of neurotransmitter.", "content": "When a pair of stimuli separated by an appropriate interval is given to the right visceropleural connective of Aplysia californica the amplitude of the second EPSP elicited in cell R15 is usually smaller than the amplitude of the first EPSP. In the present paper we show that this phenomenon, synaptic depression, can be analyzed in terms of the material flow model of neurotransmitter economics developed in our preceding publications. We specifically show how changes in the 4 model parameters; A, the available pool of transmitter; F, the fraction of the available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; and D, the rate constant of demobilization of transmitter from the available pool, all effect synaptic depression. In addition, we show how transient changes in F and M, that are observed immediately and for seconds after a stimulus, influence the time course of synaptic depression. Using this analysis we then tested our previous inferences about changes in the model parameters produced either by pharmacological manipulations or repetitive stimulation, by comparing the observed effects of these manipulations on synaptic depression with the theoretical predictions. The theoretical and experimental findings agreed, thereby strengthening both our previous conclusions of the mode of action of these manipulations and the model itself.", "contents": "Synaptic depression at a synapse in Aplysia californica: analysis in terms of a material flow model of neurotransmitter. When a pair of stimuli separated by an appropriate interval is given to the right visceropleural connective of Aplysia californica the amplitude of the second EPSP elicited in cell R15 is usually smaller than the amplitude of the first EPSP. In the present paper we show that this phenomenon, synaptic depression, can be analyzed in terms of the material flow model of neurotransmitter economics developed in our preceding publications. We specifically show how changes in the 4 model parameters; A, the available pool of transmitter; F, the fraction of the available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; and D, the rate constant of demobilization of transmitter from the available pool, all effect synaptic depression. In addition, we show how transient changes in F and M, that are observed immediately and for seconds after a stimulus, influence the time course of synaptic depression. Using this analysis we then tested our previous inferences about changes in the model parameters produced either by pharmacological manipulations or repetitive stimulation, by comparing the observed effects of these manipulations on synaptic depression with the theoretical predictions. The theoretical and experimental findings agreed, thereby strengthening both our previous conclusions of the mode of action of these manipulations and the model itself."}
{"id": "PMID:6121", "title": "Biochemical differentiation of mechanically dissociated mammalian brain in aggregating cell culture.", "content": "Mouse and rat brain cells were dissociated by a simple mechanical sieving technique and studied in culture for the formation of aggregates and the activities of choline acetyltransferase, acetylcholinesterase, glutamic acid decarboxylase, tyrosine 3-monooxygenase, aromatic L-amino acid decarboxylase, catechol methyltransferase, and monoamine oxidase. Cells from fetal and neonatal tissue formed aggregates but not cells from tissue older than two days after birth. The pattern of development of enzyme activities in these aggregates varied with the age of starting tissue. The highest levels of specific activity for the neuron-specific enzymes were found after 3-4 weeks in culture for aggregates of cells derived from relatively undeveloped brains.", "contents": "Biochemical differentiation of mechanically dissociated mammalian brain in aggregating cell culture. Mouse and rat brain cells were dissociated by a simple mechanical sieving technique and studied in culture for the formation of aggregates and the activities of choline acetyltransferase, acetylcholinesterase, glutamic acid decarboxylase, tyrosine 3-monooxygenase, aromatic L-amino acid decarboxylase, catechol methyltransferase, and monoamine oxidase. Cells from fetal and neonatal tissue formed aggregates but not cells from tissue older than two days after birth. The pattern of development of enzyme activities in these aggregates varied with the age of starting tissue. The highest levels of specific activity for the neuron-specific enzymes were found after 3-4 weeks in culture for aggregates of cells derived from relatively undeveloped brains."}
{"id": "PMID:6124", "title": "Stimulation of tyrosine hydroxylase activity by cyclic AMP in synaptosomes and in soluble striatal enzyme preparations.", "content": "Dibutyryl cyclic AMP (dB-cAMP) elicits a concentration-dependent stimulation of tyrosine hydroxylase activity in the striatal and mesolimbic synaptosomes. The per cent of stimulation is significantly higher in the mesolimbic synaptosomes than in the striatal synaptosomes. dB-cAMP and depolarizing agents (ouabain or veratridine) have an additive effect on synaptosomal tyrosine hydroxylase activity, indicating that they stimulate tyrosine hydroxylase activity by different mechanisms. cAMP does not stimulate soluble striatal tyrosine hydroxylase activity unless it is added in combination with ATP and Mg2+, compounds required for the activity of cAMP-dependent protein kinase. The cAMP elicited per cent stimulation of soluble tyrosine hydroxylase activity is dependent upon the concentration of added protein kinase and upon the pH of the reaction. dB-cAMP has the same effect on the kinetic state of tyrosine hydroxylase in synaptosomes as cAMP on the soluble tyrosine hydroxylase. The nucleotide does not alter the apparent Km for tyrosine, reduces the Km for the pteridine cofactor and increases the Ki for dopamine. Thus, cAMP increases the affinity of tyrosine hydroxylase for the pteridine cofactor and concomitantly decreases the affinity for the end-product inhibition.", "contents": "Stimulation of tyrosine hydroxylase activity by cyclic AMP in synaptosomes and in soluble striatal enzyme preparations. Dibutyryl cyclic AMP (dB-cAMP) elicits a concentration-dependent stimulation of tyrosine hydroxylase activity in the striatal and mesolimbic synaptosomes. The per cent of stimulation is significantly higher in the mesolimbic synaptosomes than in the striatal synaptosomes. dB-cAMP and depolarizing agents (ouabain or veratridine) have an additive effect on synaptosomal tyrosine hydroxylase activity, indicating that they stimulate tyrosine hydroxylase activity by different mechanisms. cAMP does not stimulate soluble striatal tyrosine hydroxylase activity unless it is added in combination with ATP and Mg2+, compounds required for the activity of cAMP-dependent protein kinase. The cAMP elicited per cent stimulation of soluble tyrosine hydroxylase activity is dependent upon the concentration of added protein kinase and upon the pH of the reaction. dB-cAMP has the same effect on the kinetic state of tyrosine hydroxylase in synaptosomes as cAMP on the soluble tyrosine hydroxylase. The nucleotide does not alter the apparent Km for tyrosine, reduces the Km for the pteridine cofactor and increases the Ki for dopamine. Thus, cAMP increases the affinity of tyrosine hydroxylase for the pteridine cofactor and concomitantly decreases the affinity for the end-product inhibition."}
{"id": "PMID:6125", "title": "Choline acetyltransferase, glutamate decarboxylase and tyrosine hydroxylase in the cochlea and cochlear nucleus of the guinea pig.", "content": "Activities of choline acetyltransferase (ChAC), glutamate decarboxylase (GAD) and tyrosine hydroxylase (TH), enzymes catalyzing the synthesis of acetylcholine (ACh), gamma-aminobutyric acid (GABA) and catecholamines, respectively, were measured in the cochlea and cochlear nucleus of the guinea pig. ChAc activity in the organ of Corti, third turn, was 1270 pmole ACh formed/min/mg protein (ChAc, 1270) and was higher than in turn 4 (ChAc, 543). ChAc activity was higher when the preparation included the inner hair cell region than when not. GAD activity in samples of turn 3 and 4 combined was low, 0.17 nmole GABA formed/min/mg protein (GAD, 0.17). All 3 enzymes were low in auditory nerve: ChAc, 1.7, GAD, 0.10 and TH, 1.0 pmole DOPA formed/min/mg protein. In the cochlear nucleus, the values were: ChAc, 129, GAD, 1.70 and TH, 2.7. The findings on the distribution of ChAc activity in the organ of Corti fit the hypothesis that the olivocochlear nerve fibers are cholinergic. Because of low GAD in the cochlea, GABA is unlikely to be transmitter in the organ of Corti. Similarly, it is unlikely that ACh, GABA or a catecholamine is a transmitter between the auditory nerve and the cochlear nucleus.", "contents": "Choline acetyltransferase, glutamate decarboxylase and tyrosine hydroxylase in the cochlea and cochlear nucleus of the guinea pig. Activities of choline acetyltransferase (ChAC), glutamate decarboxylase (GAD) and tyrosine hydroxylase (TH), enzymes catalyzing the synthesis of acetylcholine (ACh), gamma-aminobutyric acid (GABA) and catecholamines, respectively, were measured in the cochlea and cochlear nucleus of the guinea pig. ChAc activity in the organ of Corti, third turn, was 1270 pmole ACh formed/min/mg protein (ChAc, 1270) and was higher than in turn 4 (ChAc, 543). ChAc activity was higher when the preparation included the inner hair cell region than when not. GAD activity in samples of turn 3 and 4 combined was low, 0.17 nmole GABA formed/min/mg protein (GAD, 0.17). All 3 enzymes were low in auditory nerve: ChAc, 1.7, GAD, 0.10 and TH, 1.0 pmole DOPA formed/min/mg protein. In the cochlear nucleus, the values were: ChAc, 129, GAD, 1.70 and TH, 2.7. The findings on the distribution of ChAc activity in the organ of Corti fit the hypothesis that the olivocochlear nerve fibers are cholinergic. Because of low GAD in the cochlea, GABA is unlikely to be transmitter in the organ of Corti. Similarly, it is unlikely that ACh, GABA or a catecholamine is a transmitter between the auditory nerve and the cochlear nucleus."}
{"id": "PMID:6128", "title": "An evaluation of L-glutamate as the transmitter released from optic nerve terminals of the pigeon.", "content": "The possibility was investigated that L-glutamic acid is the excitatory transmitter released from the optic nerve terminals of the pigeon optic tectum. (1) Superficial layers of the tectum contained high levels of endogenous glutamate and accumulated L-[3H]glutamate by a high affinity uptake process. (2) Subcellular and autoradiographic studies indicated that 10-30% of the exogenously accumulated L-[3H]glutamate was localized within synaptosomes, and that 11-15% of the synaptosomes had been labelled. (3) The glutamate-accumulating synaptosomes sedimented to the same isopycnic density as pinched-off optic nerve terminals. (4) GABA-and noradrenaline-accumulating synaptosomes were also associated with this subcellular population. (5) Retinal ablation did not change endogenous glutamate concentrations or the high affinity uptake of glutamate. The results are discussed in relation to a possible role for L-glutamate as the 'optic nerve transmitter' and in the context of previous evidence implicating glutamate as an excitatory transmitter.", "contents": "An evaluation of L-glutamate as the transmitter released from optic nerve terminals of the pigeon. The possibility was investigated that L-glutamic acid is the excitatory transmitter released from the optic nerve terminals of the pigeon optic tectum. (1) Superficial layers of the tectum contained high levels of endogenous glutamate and accumulated L-[3H]glutamate by a high affinity uptake process. (2) Subcellular and autoradiographic studies indicated that 10-30% of the exogenously accumulated L-[3H]glutamate was localized within synaptosomes, and that 11-15% of the synaptosomes had been labelled. (3) The glutamate-accumulating synaptosomes sedimented to the same isopycnic density as pinched-off optic nerve terminals. (4) GABA-and noradrenaline-accumulating synaptosomes were also associated with this subcellular population. (5) Retinal ablation did not change endogenous glutamate concentrations or the high affinity uptake of glutamate. The results are discussed in relation to a possible role for L-glutamate as the 'optic nerve transmitter' and in the context of previous evidence implicating glutamate as an excitatory transmitter."}
{"id": "PMID:6130", "title": "[Hemodynamic modifications induced by hypoxia in the dog].", "content": "In non hypercapnic hypoxia (inhalation of a 4,5% O2 mixture during 10 minutes) blood pressure, heart rate, cardiac output, femoral and carotid blood flow inhance so that, in less extent, vertebral blood flow. Such a reaction is consequent with an hypoxic stimulation of adrenal glands.", "contents": "[Hemodynamic modifications induced by hypoxia in the dog]. In non hypercapnic hypoxia (inhalation of a 4,5% O2 mixture during 10 minutes) blood pressure, heart rate, cardiac output, femoral and carotid blood flow inhance so that, in less extent, vertebral blood flow. Such a reaction is consequent with an hypoxic stimulation of adrenal glands."}
{"id": "PMID:6131", "title": "[Respiratory stimulant effect of S 2620 in the dog anesthetized with pentobarbital].", "content": "In the dog under pentobarbitone anesthesia, the intravenous injection of 1 mg/kg S 2620 is followed by a significant increase in respiratory rate, PaO2 and pHa and by a large decrease in PaCO2. Cervical vagotomy and chemoreceptor denervation reduced and even abolished these effects. They can be induced again by a second intravenous injection or by direct instillation in the fourth ventricle. These results suggest a central action of the drug.", "contents": "[Respiratory stimulant effect of S 2620 in the dog anesthetized with pentobarbital]. In the dog under pentobarbitone anesthesia, the intravenous injection of 1 mg/kg S 2620 is followed by a significant increase in respiratory rate, PaO2 and pHa and by a large decrease in PaCO2. Cervical vagotomy and chemoreceptor denervation reduced and even abolished these effects. They can be induced again by a second intravenous injection or by direct instillation in the fourth ventricle. These results suggest a central action of the drug."}
{"id": "PMID:6132", "title": "Modification of the regulatory properties of pyruvate kinase of Neurospora by growth at elevated temperatures.", "content": "Pyruvate kinase (EC 2.7.1.40) was isolated from Neurospora crassa mycelium grown at 28 degrees C (PK-28) and at 42 degrees C (PK-42). The regulatory properties, particularly the response towards the allosteric effector fructose 1,6-diphosphate (FDP), was different in the two enzymes. PK-28 showed an activation by FDP but PK-42, under comparable conditions, appeared to be activated by low concentrations of FDP and inhibited by higher ones. For PK-28, complex formation with FDP results in a lowering of the isoelectric point from 6.40 to 5.50, representing the pI of the unliganded enzyme and that of the complex, respectively. In contrast to this, PK-42 exhibits a weak binding to FDP as suggested by a lack of decrease in the isoelectric point on treatment with comparable concentrations of FDP. Studies with quenching of aromatic residue fluorescence of PK-28 and PK-42, following binding of FDP, indicate that although this ligand binds to both types of enzymes the affinity for the two is vastly different. Dissociation constants of 9.3 muM and 0.1 mM were calculated for the binding of FDP to PK-28 and PK-42, respectively. It is concluded that growth at elevated temperatures induced a conformational change in the pyruvate kinase leading to partial desensitization of the allosteric site. The nature of the factor(s) responsible for this change is not understood at present.", "contents": "Modification of the regulatory properties of pyruvate kinase of Neurospora by growth at elevated temperatures. Pyruvate kinase (EC 2.7.1.40) was isolated from Neurospora crassa mycelium grown at 28 degrees C (PK-28) and at 42 degrees C (PK-42). The regulatory properties, particularly the response towards the allosteric effector fructose 1,6-diphosphate (FDP), was different in the two enzymes. PK-28 showed an activation by FDP but PK-42, under comparable conditions, appeared to be activated by low concentrations of FDP and inhibited by higher ones. For PK-28, complex formation with FDP results in a lowering of the isoelectric point from 6.40 to 5.50, representing the pI of the unliganded enzyme and that of the complex, respectively. In contrast to this, PK-42 exhibits a weak binding to FDP as suggested by a lack of decrease in the isoelectric point on treatment with comparable concentrations of FDP. Studies with quenching of aromatic residue fluorescence of PK-28 and PK-42, following binding of FDP, indicate that although this ligand binds to both types of enzymes the affinity for the two is vastly different. Dissociation constants of 9.3 muM and 0.1 mM were calculated for the binding of FDP to PK-28 and PK-42, respectively. It is concluded that growth at elevated temperatures induced a conformational change in the pyruvate kinase leading to partial desensitization of the allosteric site. The nature of the factor(s) responsible for this change is not understood at present."}
{"id": "PMID:6133", "title": "Modified 5'-nucleotides resistant to 5'-nucleotidase: isolation of 3-(3-amino-3-carboxypropyl) uridine 5'-phosphate and N2, N2-dimethylguanosine 5'-phosphate from snake venom hydrolysates of transfer RNA.", "content": "A procedure for the quantitative measurement of the O2'-methylnucleoside constitutents of RNA has recently been developed in this laboratory (Gray, M.W. Can. J. Biochem. 53, 735-746 (1975)). This assay method is based on the resistance of O2'-methylnucleoside 5'-phosphates (pNm) (generated by phosphodiesterase hydrolysis of RNA) to subsequent dephosphorylation by venom 5'-nucleotidase (EC 3.1.3.5). In the present investigation, two base-modified 5'-nucleotides, each displaying an unusual resistance to 5'-nucleotidase, have been identified. These compounds have been characterized by a variety of techniques as N2, N2-dimethylguanosine 5'-phosphate (pm2/2G) and 3-(3-amino-3-carboxypropyl)uridine 5'-phosphate (p4abu3U). Because of their resistance to 5'-nucleotidase, pm2/2G and p4abu3U are isolated along with the pNm in the mononucleotide fraction of venom hydrolysates of transfer RNA. Under hydrolysis conditions, the stability of p4abu3U is comparable to that of a pNm, allowing quantitative assay of the nucleotide. The proportion (mean +/- SD) of p4abu3U in venom hydrolysates of wheat embryo and Escherichia coli tRNA has been determined to be 0.35 +/- 0.03 (n=5) and 0.14 +/- 0.02 (n=4) mol%, respectively. The absence of p4abu3U in venom hydrolysates of yeast tRNA implies the absence of the corresponding nucleoside in yeast tRNA, in agreement with existing data. The variable recovery of pm2/2G from venom hydrolysates of wheat embryo and yeast tRNA indicates that under hydrolysis conditions, this base-modified nucleotide is only partially resistent to 5'-nucleotidase. The complete absence of pm2/2G in venom hydrolysates of E. coli tRNA is consistent with the known absence of N2, N2-dimethylguanosine in this RNA. These observations demonstrate that resistance to 5'-nucleotidase is a necessary but not sufficient criterion for concluding that a 5'-nucleotide is O2'-methylated. When applied to wheat embryo ribosomal RNA, the analytical methods described in this report failed to reveal any compound having the distinctive charge properties of p4abu3U. It therefore appears that 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine, recently characterized as a constituent of the 18 S rRNA of Chinese hamster cells (Saponara, A.G. & Enger, M.D. Biochim. Biophys. Acta 349, 61-77 (1974)), may not be present in wheat embryo ribosomal RNA.", "contents": "Modified 5'-nucleotides resistant to 5'-nucleotidase: isolation of 3-(3-amino-3-carboxypropyl) uridine 5'-phosphate and N2, N2-dimethylguanosine 5'-phosphate from snake venom hydrolysates of transfer RNA. A procedure for the quantitative measurement of the O2'-methylnucleoside constitutents of RNA has recently been developed in this laboratory (Gray, M.W. Can. J. Biochem. 53, 735-746 (1975)). This assay method is based on the resistance of O2'-methylnucleoside 5'-phosphates (pNm) (generated by phosphodiesterase hydrolysis of RNA) to subsequent dephosphorylation by venom 5'-nucleotidase (EC 3.1.3.5). In the present investigation, two base-modified 5'-nucleotides, each displaying an unusual resistance to 5'-nucleotidase, have been identified. These compounds have been characterized by a variety of techniques as N2, N2-dimethylguanosine 5'-phosphate (pm2/2G) and 3-(3-amino-3-carboxypropyl)uridine 5'-phosphate (p4abu3U). Because of their resistance to 5'-nucleotidase, pm2/2G and p4abu3U are isolated along with the pNm in the mononucleotide fraction of venom hydrolysates of transfer RNA. Under hydrolysis conditions, the stability of p4abu3U is comparable to that of a pNm, allowing quantitative assay of the nucleotide. The proportion (mean +/- SD) of p4abu3U in venom hydrolysates of wheat embryo and Escherichia coli tRNA has been determined to be 0.35 +/- 0.03 (n=5) and 0.14 +/- 0.02 (n=4) mol%, respectively. The absence of p4abu3U in venom hydrolysates of yeast tRNA implies the absence of the corresponding nucleoside in yeast tRNA, in agreement with existing data. The variable recovery of pm2/2G from venom hydrolysates of wheat embryo and yeast tRNA indicates that under hydrolysis conditions, this base-modified nucleotide is only partially resistent to 5'-nucleotidase. The complete absence of pm2/2G in venom hydrolysates of E. coli tRNA is consistent with the known absence of N2, N2-dimethylguanosine in this RNA. These observations demonstrate that resistance to 5'-nucleotidase is a necessary but not sufficient criterion for concluding that a 5'-nucleotide is O2'-methylated. When applied to wheat embryo ribosomal RNA, the analytical methods described in this report failed to reveal any compound having the distinctive charge properties of p4abu3U. It therefore appears that 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine, recently characterized as a constituent of the 18 S rRNA of Chinese hamster cells (Saponara, A.G. & Enger, M.D. Biochim. Biophys. Acta 349, 61-77 (1974)), may not be present in wheat embryo ribosomal RNA."}
{"id": "PMID:6134", "title": "Kinetic effect of some aliphatic amines on yeast alcohol dehydrogenase.", "content": "Initial rate studies of ethanol oxidation catalyzed by yeast alcohol dehydrogenase (EC 1.1.1.1) were carried out in the presence of varying concentrations of aliphatic amines over the pH range from 8.0 to 10.5. Aliphatic amines either activate or inhibit the enzyme depending on whether the pH is greater or less than 9.5 suggesting that the protonated amines activate and the nonprotonated amines inhibit the enzyme. Aliphatic amines activate yeast alcohol dehydrogenase by decreasing Kb while they inhibit the enzyme by increasing both Ka and Kia. When both protonated and nonprotonated amines are present in solution, either overall activation or inhibition will be observed depending on the relative concentration of the two amine species.", "contents": "Kinetic effect of some aliphatic amines on yeast alcohol dehydrogenase. Initial rate studies of ethanol oxidation catalyzed by yeast alcohol dehydrogenase (EC 1.1.1.1) were carried out in the presence of varying concentrations of aliphatic amines over the pH range from 8.0 to 10.5. Aliphatic amines either activate or inhibit the enzyme depending on whether the pH is greater or less than 9.5 suggesting that the protonated amines activate and the nonprotonated amines inhibit the enzyme. Aliphatic amines activate yeast alcohol dehydrogenase by decreasing Kb while they inhibit the enzyme by increasing both Ka and Kia. When both protonated and nonprotonated amines are present in solution, either overall activation or inhibition will be observed depending on the relative concentration of the two amine species."}
{"id": "PMID:6135", "title": "Purine catabolism in man: characterization of placental microsomal 5'-nucleotidase.", "content": "Human placental microsomal 5'-nucleotidase (EC 3.1.3.5) was prepared free of alkaline phosphatase by isoelectric focusing. A total of seven electrophoretic variants were isolated during the preparation of six placentas. Only three to six variants were found in a single placenta. The isoelectric pH's were 6.70, 6.44, 6.23, 6.02, 5.76, 5.63 and 5.44. These were found to be composed of variable quantities of a large, medium and low molecular weight form. The apparent molecular weights of the medium and light form of the enzyme were 86 500 and 43 500, respectively, as estimated from Stokes radius and sedimentation velocity determinations. The electrophoretic variants were not distinguishable with respect to specific activity and Michaelis constants for AMP, GMP or CMP or inhibition by ATP, CTP or adenosine. These electrophoretic variants appeared to be pseudoisozymes based upon different states of aggregation of a common primary sequence. There was a wide range of substrate specificity among nucleoside 5'-monophosphates which included 2-deoxyribose compounds. With AMP as 100, substrate activity was: CMP, 122; NMN, 74; GMP, 68: IMP, 63; XMP, 28 and UDP-glucose, 68. The Michaelis constants for AMP, GMP and CMP ranged from 12-18 muM, from 33-67 muM and from 170-250 muM, respectively. Although 5'-nucleotidase was active in the absence of divalent cation, 5 mM MgCl2 stimulated the enzyme activity to 234% of control and shifted the pH optimum of 9.8 to a plateau from pH 7.4-9.8.", "contents": "Purine catabolism in man: characterization of placental microsomal 5'-nucleotidase. Human placental microsomal 5'-nucleotidase (EC 3.1.3.5) was prepared free of alkaline phosphatase by isoelectric focusing. A total of seven electrophoretic variants were isolated during the preparation of six placentas. Only three to six variants were found in a single placenta. The isoelectric pH's were 6.70, 6.44, 6.23, 6.02, 5.76, 5.63 and 5.44. These were found to be composed of variable quantities of a large, medium and low molecular weight form. The apparent molecular weights of the medium and light form of the enzyme were 86 500 and 43 500, respectively, as estimated from Stokes radius and sedimentation velocity determinations. The electrophoretic variants were not distinguishable with respect to specific activity and Michaelis constants for AMP, GMP or CMP or inhibition by ATP, CTP or adenosine. These electrophoretic variants appeared to be pseudoisozymes based upon different states of aggregation of a common primary sequence. There was a wide range of substrate specificity among nucleoside 5'-monophosphates which included 2-deoxyribose compounds. With AMP as 100, substrate activity was: CMP, 122; NMN, 74; GMP, 68: IMP, 63; XMP, 28 and UDP-glucose, 68. The Michaelis constants for AMP, GMP and CMP ranged from 12-18 muM, from 33-67 muM and from 170-250 muM, respectively. Although 5'-nucleotidase was active in the absence of divalent cation, 5 mM MgCl2 stimulated the enzyme activity to 234% of control and shifted the pH optimum of 9.8 to a plateau from pH 7.4-9.8."}
{"id": "PMID:6136", "title": "Ethanol metabolism by the rat heart and alcohol dehydrogenase activity.", "content": "Rat hearts perfused with oxygenated buffer containing [1-14C]ethanol metabolized small amounts of the ethanol to carbon dioxide. Very sensitive techniques are required to separate the resulting 14CO2 from the ethanol. This metabolism is not inhibited by levels of pyrazole which markedly inhibit NAD dependent liver alcohol dehydrogenase (EC 1.1.1.1). In vitro studies suggest that NADP functions as a cofactor for the rat heart alcohol dehydrogenase activity of crude heart homogenates. The kinetics parameters, the specific activity, and the pH dependence of the enzyme activity measured in these experiments suggest that it may have a minor role in ethanol metabolism by the rat.", "contents": "Ethanol metabolism by the rat heart and alcohol dehydrogenase activity. Rat hearts perfused with oxygenated buffer containing [1-14C]ethanol metabolized small amounts of the ethanol to carbon dioxide. Very sensitive techniques are required to separate the resulting 14CO2 from the ethanol. This metabolism is not inhibited by levels of pyrazole which markedly inhibit NAD dependent liver alcohol dehydrogenase (EC 1.1.1.1). In vitro studies suggest that NADP functions as a cofactor for the rat heart alcohol dehydrogenase activity of crude heart homogenates. The kinetics parameters, the specific activity, and the pH dependence of the enzyme activity measured in these experiments suggest that it may have a minor role in ethanol metabolism by the rat."}
{"id": "PMID:6137", "title": "The effect of pH on rabbit atrial response to histamine.", "content": "The chorontropic response of isolated rabbit atria in normal Tyrode's medium increases monotonically with increasing doses of histamine (9 X 10-7 -9 X 10-4 M). Plots of the inverse of response against the inverse of concentration were linear; and from these plots were derived values fro the theoretical maximum response at 'infinite' dose and for pH histamine concentration required to evoke a half maximum response. Alteration of pH by changing (HCO3-) at a constant pCO2, (Na) and osolality did not appreciably affect the response to histamine in the range pH 7.0-7.6. However, at pH below 7.0 the magnitude of histamine response was reduced at all concentrations of histamine tested. In the pH range 7.0-7.6, additions of NaHCO3 at constant pCO2 increased the spontaneous rate of rabbit atria (in the absence of histamine); however, there was little effect of changing pH (in this range) by altering (HCO3-) at constant pCO2 when (Na+) and osmolaity were kept constant. Immersion in solutions at pH's less than 7.0 led to decline in spontaneous rate and force contraction. It is probable that depression of adenyl cyclase activity rather than a specific change in ionization of histamine receptor is responsible for a decreased response to histamine at pH 6.9.", "contents": "The effect of pH on rabbit atrial response to histamine. The chorontropic response of isolated rabbit atria in normal Tyrode's medium increases monotonically with increasing doses of histamine (9 X 10-7 -9 X 10-4 M). Plots of the inverse of response against the inverse of concentration were linear; and from these plots were derived values fro the theoretical maximum response at 'infinite' dose and for pH histamine concentration required to evoke a half maximum response. Alteration of pH by changing (HCO3-) at a constant pCO2, (Na) and osolality did not appreciably affect the response to histamine in the range pH 7.0-7.6. However, at pH below 7.0 the magnitude of histamine response was reduced at all concentrations of histamine tested. In the pH range 7.0-7.6, additions of NaHCO3 at constant pCO2 increased the spontaneous rate of rabbit atria (in the absence of histamine); however, there was little effect of changing pH (in this range) by altering (HCO3-) at constant pCO2 when (Na+) and osmolaity were kept constant. Immersion in solutions at pH's less than 7.0 led to decline in spontaneous rate and force contraction. It is probable that depression of adenyl cyclase activity rather than a specific change in ionization of histamine receptor is responsible for a decreased response to histamine at pH 6.9."}
{"id": "PMID:6138", "title": "Selective enrichment of Shigella in the presence of Escherichia coli by use of 4-chloro-2-cyclopentylphenyl beta-D-galactopyranoside.", "content": "A procedure involving the use of citrate-buffered lactose broth (pH 6.5) containing an analogue of a beta-galactoside (4-chloro-2-cyclopentylphenyl beta-D-galactopyranoside) has been developed for the enrichment of Shigella in competition with a 100-fold higher population of Escherichia coli. The system makes use of the beta-galactosidase activity of E. coli which hydrolyzes the phenolic derivative of beta-galactoside to galactose and an aglycone moiety (4-chloro-2-cyclopentylphenol) which is toxic to E. coli but is tolerated by Shigella. The procedure is particularly effective in the enrichment of S. sonnei and S. flexneri; S. dynsenteriae and S. boydii are enriched to a lesser extent.", "contents": "Selective enrichment of Shigella in the presence of Escherichia coli by use of 4-chloro-2-cyclopentylphenyl beta-D-galactopyranoside. A procedure involving the use of citrate-buffered lactose broth (pH 6.5) containing an analogue of a beta-galactoside (4-chloro-2-cyclopentylphenyl beta-D-galactopyranoside) has been developed for the enrichment of Shigella in competition with a 100-fold higher population of Escherichia coli. The system makes use of the beta-galactosidase activity of E. coli which hydrolyzes the phenolic derivative of beta-galactoside to galactose and an aglycone moiety (4-chloro-2-cyclopentylphenol) which is toxic to E. coli but is tolerated by Shigella. The procedure is particularly effective in the enrichment of S. sonnei and S. flexneri; S. dynsenteriae and S. boydii are enriched to a lesser extent."}
{"id": "PMID:6139", "title": "Adsorption, desorption, and activity of glucose oxidase on selected clay species.", "content": "The adsorption of the enzyme glucose oxidase (EC 1.1.3.4) to clays followed the pattern described for other proteins as being pH dependent. Maximum adsorption occurred at or below the isoelectric point of the enzyme. The amount of enzyme adsorbed to clay was influenced by the type of clay used, and also the saturating cations. Initially adsorbed enzyme showed low specific activities, and as amounts of enzyme adsorbed approached maximum stauration of clay, specific activities increased approaching that determined for free enzyme. The adsorption of glucose oxidase involved a temperature-independent cation-exchange mechanism, and enzyme adsorbed to surfaces of clay could be desorbed in active form by elevation of pH of suspending solution. This was followed by a slower temperature-dependent fixation, probably by hydrogen bonding, which resulted in protein being irreversibly adsorbed to clay surfaces. It is proposed that on adsorption of glucose oxidase to clay surfaces unravelling of the protein structure occurred, which allowed penetration of protein into the interlamellar spaces of montmorillonite. This proposal was based on the observed expansion of montmorillonite to 23 A, and the decreases in amount of a second-protein lysozyme adsorbed with extended incubation times of glucose oxidase - clay complexes at pH 4.5.", "contents": "Adsorption, desorption, and activity of glucose oxidase on selected clay species. The adsorption of the enzyme glucose oxidase (EC 1.1.3.4) to clays followed the pattern described for other proteins as being pH dependent. Maximum adsorption occurred at or below the isoelectric point of the enzyme. The amount of enzyme adsorbed to clay was influenced by the type of clay used, and also the saturating cations. Initially adsorbed enzyme showed low specific activities, and as amounts of enzyme adsorbed approached maximum stauration of clay, specific activities increased approaching that determined for free enzyme. The adsorption of glucose oxidase involved a temperature-independent cation-exchange mechanism, and enzyme adsorbed to surfaces of clay could be desorbed in active form by elevation of pH of suspending solution. This was followed by a slower temperature-dependent fixation, probably by hydrogen bonding, which resulted in protein being irreversibly adsorbed to clay surfaces. It is proposed that on adsorption of glucose oxidase to clay surfaces unravelling of the protein structure occurred, which allowed penetration of protein into the interlamellar spaces of montmorillonite. This proposal was based on the observed expansion of montmorillonite to 23 A, and the decreases in amount of a second-protein lysozyme adsorbed with extended incubation times of glucose oxidase - clay complexes at pH 4.5."}
{"id": "PMID:6140", "title": "Inhibition of growth, iron, and sulfur oxidation in Thiobacillus ferrooxidans by simple organic compounds.", "content": "Iron and sulfur oxidation by Thiobacillus ferrooxidans as well as growth on ferrous iron were inhibited by a variety of low molecular weight organic compounds. The influences of chemical structure of the organic inhibitors, pH, temperature, physical treatment of cells, and added inhibitory or stimulatory inorganic ions and iron oxidation suggest that a major factor contributing to the inhibitory effects on iron oxidation is the relative electronegativity of the organic molecule. The data also suggest that inhibitory organic compounds may (i) directly affect the iron-oxidizing enzyme system, (ii) react abiologically with ferrous iron outside the cell, (iii) interfere with the roles of phosphate and sulfate in iron oxidation, and (iv) nonselectively disrupt the cell envelope or membrane.", "contents": "Inhibition of growth, iron, and sulfur oxidation in Thiobacillus ferrooxidans by simple organic compounds. Iron and sulfur oxidation by Thiobacillus ferrooxidans as well as growth on ferrous iron were inhibited by a variety of low molecular weight organic compounds. The influences of chemical structure of the organic inhibitors, pH, temperature, physical treatment of cells, and added inhibitory or stimulatory inorganic ions and iron oxidation suggest that a major factor contributing to the inhibitory effects on iron oxidation is the relative electronegativity of the organic molecule. The data also suggest that inhibitory organic compounds may (i) directly affect the iron-oxidizing enzyme system, (ii) react abiologically with ferrous iron outside the cell, (iii) interfere with the roles of phosphate and sulfate in iron oxidation, and (iv) nonselectively disrupt the cell envelope or membrane."}
{"id": "PMID:6141", "title": "Regulation of acetyl-CoA synthetase of Saccharomyces cerevisiae.", "content": "Acetyl-coenzyme A synthetase (EC 6.2.1.1) activity of Saccharomyces cerevisiae was determined by a radioactive assay procedure. The activity in vitro was inhibited significantly by NADPH, NADH, or AMP and to a lesser extent by NADP, NAD, or ADP. Glutamic acid and alpha-ketoglutaric acid were not inhibitory. The enzyme level was repressed when the cells were grown in a complex nutrient medium as opposed to the minimal medium. However, a glutamic acid auxotroph glul, when grown in excess glutamic acid, demonstrated a fivefold increase of acetyl-CoA synthetase.", "contents": "Regulation of acetyl-CoA synthetase of Saccharomyces cerevisiae. Acetyl-coenzyme A synthetase (EC 6.2.1.1) activity of Saccharomyces cerevisiae was determined by a radioactive assay procedure. The activity in vitro was inhibited significantly by NADPH, NADH, or AMP and to a lesser extent by NADP, NAD, or ADP. Glutamic acid and alpha-ketoglutaric acid were not inhibitory. The enzyme level was repressed when the cells were grown in a complex nutrient medium as opposed to the minimal medium. However, a glutamic acid auxotroph glul, when grown in excess glutamic acid, demonstrated a fivefold increase of acetyl-CoA synthetase."}
{"id": "PMID:6142", "title": "beta-Galactosidase from Bacillus stearothermophilus.", "content": "Several strains of thermophilic aerobic spore-forming bacilli synthesize beta-galactosidase (EC 3.2.1.23) constitutively. The constitutivity is apparently not the result of a temperature-sensitive repressor. The beta-galactosidase from one strain, investigated in cell-free extracts, has a pH optimum between 6.0 and 6.4 and a very sharp pH dependence on the acid side of its optimum. The optimum temperature for this enzyme is 65 degrees C and the Arrhenius activation energy is about 24 kcal/mol below 47 degrees C and 16 kcal/mol above that temperature. At 55 degrees C the Km is 0.11 M for lactose and 9.8 X 10(-3) M for 9-nitrophenyl-beta-D-galactopyranoside. The enzyme is strongly product-inhibited by galactose (Ki equals 2.5 X 10(-3) M). It is relatively stable at 50 degrees C, losing only half of its activity after 20 days at this temperature. At 60 degrees C more than 60% of the activity is lost in 10 min. However, the enzyme is protected somewhat against thermal inactivation by protein, and in the presence of 4 mg/ml of bovine serum albumin the enzyme is only 18% inactivated in 10 min at 60 degrees C. Its molecular weight, estimated by disc gel electrophoresis, is 215 000.", "contents": "beta-Galactosidase from Bacillus stearothermophilus. Several strains of thermophilic aerobic spore-forming bacilli synthesize beta-galactosidase (EC 3.2.1.23) constitutively. The constitutivity is apparently not the result of a temperature-sensitive repressor. The beta-galactosidase from one strain, investigated in cell-free extracts, has a pH optimum between 6.0 and 6.4 and a very sharp pH dependence on the acid side of its optimum. The optimum temperature for this enzyme is 65 degrees C and the Arrhenius activation energy is about 24 kcal/mol below 47 degrees C and 16 kcal/mol above that temperature. At 55 degrees C the Km is 0.11 M for lactose and 9.8 X 10(-3) M for 9-nitrophenyl-beta-D-galactopyranoside. The enzyme is strongly product-inhibited by galactose (Ki equals 2.5 X 10(-3) M). It is relatively stable at 50 degrees C, losing only half of its activity after 20 days at this temperature. At 60 degrees C more than 60% of the activity is lost in 10 min. However, the enzyme is protected somewhat against thermal inactivation by protein, and in the presence of 4 mg/ml of bovine serum albumin the enzyme is only 18% inactivated in 10 min at 60 degrees C. Its molecular weight, estimated by disc gel electrophoresis, is 215 000."}
{"id": "PMID:6144", "title": "Transient inhibition of cell proliferation in rat glioma monolayer cultures by cortisol.", "content": "The effect of 3 muM cortisol on cell proliferation in rat glioma (strain C6) monolayer cultures was investigated. Cell density measurements showed that cortisol-treated C6 cells continued to proliferate at maximum log phase rates for 1 to 2 days. Then cell proliferation ceased as growth in control cultures continued into stationary phase. A 2-day period of growth inhibition followed during which cell densities were 30 to 50% lower relative to controls. Growth resumed subsequently, and final cell densities were similar to those of controls. The presence of epicortisol (the biologically inactive isomer of cortisol) in the culture medium did not alter the rate of log phase growth relative to controls. During the initial period of continued growth after exposure to cortisol, the pH of the medium decreased at the same rate in control and treated cultures. During the growth-inhibitory period, erythrosin B dye was excluded equally well (greater than 94%) by control and treated cells, and no morphological differences were detected by phase contrast microscopy. When the culture medium was replaced daily, the control cells at elevated densities continued to proliferate at a reduced rate. In cortisol-treated cultures, the period of growth inhibition commenced 3 days after the cells were exposed initially to cortisol. A 2-day period of growth inhibition followed during which the pH of the 1-day-old media from both control and treated cultures decreased from 7.4 to 6.9. Growth resumed subsequently in the treated cultures to produce elevated cell densities similar to those of controls. These results demonstrate that cortisol at concentrations considered chemotherapeutic in vivo exerts a transient inhibitory effect on C6 glioma cell proliferation.", "contents": "Transient inhibition of cell proliferation in rat glioma monolayer cultures by cortisol. The effect of 3 muM cortisol on cell proliferation in rat glioma (strain C6) monolayer cultures was investigated. Cell density measurements showed that cortisol-treated C6 cells continued to proliferate at maximum log phase rates for 1 to 2 days. Then cell proliferation ceased as growth in control cultures continued into stationary phase. A 2-day period of growth inhibition followed during which cell densities were 30 to 50% lower relative to controls. Growth resumed subsequently, and final cell densities were similar to those of controls. The presence of epicortisol (the biologically inactive isomer of cortisol) in the culture medium did not alter the rate of log phase growth relative to controls. During the initial period of continued growth after exposure to cortisol, the pH of the medium decreased at the same rate in control and treated cultures. During the growth-inhibitory period, erythrosin B dye was excluded equally well (greater than 94%) by control and treated cells, and no morphological differences were detected by phase contrast microscopy. When the culture medium was replaced daily, the control cells at elevated densities continued to proliferate at a reduced rate. In cortisol-treated cultures, the period of growth inhibition commenced 3 days after the cells were exposed initially to cortisol. A 2-day period of growth inhibition followed during which the pH of the 1-day-old media from both control and treated cultures decreased from 7.4 to 6.9. Growth resumed subsequently in the treated cultures to produce elevated cell densities similar to those of controls. These results demonstrate that cortisol at concentrations considered chemotherapeutic in vivo exerts a transient inhibitory effect on C6 glioma cell proliferation."}
{"id": "PMID:6145", "title": "Effects of Tumor-like assay conditions, lonizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes.", "content": "Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (43 degrees). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99% while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30%. When the P815 target cells rather than the CTL's were exposed to heat their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types: neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated P815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients.", "contents": "Effects of Tumor-like assay conditions, lonizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes. Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (43 degrees). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99% while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30%. When the P815 target cells rather than the CTL's were exposed to heat their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types: neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated P815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients."}
{"id": "PMID:6146", "title": "Conditions of cultivation required for the formation of hemicysts in vitro by rat bladder carcinoma R-4909.", "content": "Rat urinary bladder carcinoma R-4909 grew readily in vitro. In areas where saturation density occurred in the cultures, occasional hemicysts were observed. A modification of technique producing \"packed cultures\" resulted in the appearance of greater numbers of hemicysts. Four clonal isolates of R-4909 were also studied in packed culture. Clone B formed hemicysts in abundance. Clone D produced occasional hemicysts similar to the parent stock line. No hemicysts were seen in cultures of clone A or clone C. The number of hemicysts formed by clone B in packed culture was responsive to the ratio between cell number and volume of medium, to serum concentration in the medium, and to pH of the medium. The last was of particular interest since a pH of 7.8 enhanced and a pH of 6.6 inhibited hemicyst formation. The effects were all reversible. On scanning electron microscopy, we found well-developed cell membrane structures between contiguous cells. In media with sufficient serum for hemicyst formation, the articulations between cells were prominent. With low serum concentrations, hemicysts did not form and the intercellular articulations were less distinct. We interpret the formation of hemicysts as an expression of fluid transport by epithelia, a function that requires a constellation of differentiated characteristics within cells and in their level of integrated association.", "contents": "Conditions of cultivation required for the formation of hemicysts in vitro by rat bladder carcinoma R-4909. Rat urinary bladder carcinoma R-4909 grew readily in vitro. In areas where saturation density occurred in the cultures, occasional hemicysts were observed. A modification of technique producing \"packed cultures\" resulted in the appearance of greater numbers of hemicysts. Four clonal isolates of R-4909 were also studied in packed culture. Clone B formed hemicysts in abundance. Clone D produced occasional hemicysts similar to the parent stock line. No hemicysts were seen in cultures of clone A or clone C. The number of hemicysts formed by clone B in packed culture was responsive to the ratio between cell number and volume of medium, to serum concentration in the medium, and to pH of the medium. The last was of particular interest since a pH of 7.8 enhanced and a pH of 6.6 inhibited hemicyst formation. The effects were all reversible. On scanning electron microscopy, we found well-developed cell membrane structures between contiguous cells. In media with sufficient serum for hemicyst formation, the articulations between cells were prominent. With low serum concentrations, hemicysts did not form and the intercellular articulations were less distinct. We interpret the formation of hemicysts as an expression of fluid transport by epithelia, a function that requires a constellation of differentiated characteristics within cells and in their level of integrated association."}
{"id": "PMID:6147", "title": "Differential transglutaminase distribution in normal rat liver and rat hepatoma.", "content": "Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma. Over 90% of the total enzyme activity was found in the 105,000 X g supernatant of normal liver, whereas only 30% was found in this fraction of the hepatomas, the remainder being found in the particulate fraction. The is distribution pattern did not correlate with protein distribution nor did it change during cellular proliferation, since regenerating liver and embryonic tissue had the same pattern as normal liver. Cell protein was a suitable acceptor substrate for the enzyme. Kinetic analyses showed that liver and hepatoma enzymes had a similar Km and Vmax for putrescine incorporation into cell protein. Hepatoma particulate enzyme was more stable than either liver or hepatoma supernatant enzyme. The enzyme may also act as the acceptor molecule.", "contents": "Differential transglutaminase distribution in normal rat liver and rat hepatoma. Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma. Over 90% of the total enzyme activity was found in the 105,000 X g supernatant of normal liver, whereas only 30% was found in this fraction of the hepatomas, the remainder being found in the particulate fraction. The is distribution pattern did not correlate with protein distribution nor did it change during cellular proliferation, since regenerating liver and embryonic tissue had the same pattern as normal liver. Cell protein was a suitable acceptor substrate for the enzyme. Kinetic analyses showed that liver and hepatoma enzymes had a similar Km and Vmax for putrescine incorporation into cell protein. Hepatoma particulate enzyme was more stable than either liver or hepatoma supernatant enzyme. The enzyme may also act as the acceptor molecule."}
{"id": "PMID:6149", "title": "The form and function of cnidarian spirocysts. 1. Ultrastructure of the capsule exterior and relationship to the tentacle sensory surface.", "content": "The commonest intracellular organelle characteristic of the Phylum Cnidaria or Coelenterata (Subclass Zoantharia) is the spirocyst. Based on scanning and transmission electron microscopy of the tentacles of sea anemones and corals, it appears that the tip of the spirocyst is either exposed to the environment or covered by a thin plasma membrane and often has a pebbled or knobby appearance. Surrounding the spirocyst tip is a ring-like structure which seems to be formed by the junction of the enclosing cell (the spirocyte) and the tip of the spirocyst. The spirocyst thread is continuous with the capsule wall and emerges from within the apical ring during discharge. No ciliary structures appear to be associated with spirocysts. Instead, two different types of microvilli have been found: short microvilli on the spirocyte itself and long microvilli furnished by the cell or cells surrounding the spirocyte. The significance of these findings is discussed in relation to the reception of stimuli for spirocyst discharge.", "contents": "The form and function of cnidarian spirocysts. 1. Ultrastructure of the capsule exterior and relationship to the tentacle sensory surface. The commonest intracellular organelle characteristic of the Phylum Cnidaria or Coelenterata (Subclass Zoantharia) is the spirocyst. Based on scanning and transmission electron microscopy of the tentacles of sea anemones and corals, it appears that the tip of the spirocyst is either exposed to the environment or covered by a thin plasma membrane and often has a pebbled or knobby appearance. Surrounding the spirocyst tip is a ring-like structure which seems to be formed by the junction of the enclosing cell (the spirocyte) and the tip of the spirocyst. The spirocyst thread is continuous with the capsule wall and emerges from within the apical ring during discharge. No ciliary structures appear to be associated with spirocysts. Instead, two different types of microvilli have been found: short microvilli on the spirocyte itself and long microvilli furnished by the cell or cells surrounding the spirocyte. The significance of these findings is discussed in relation to the reception of stimuli for spirocyst discharge."}
{"id": "PMID:6159", "title": "[Effect of pH on bacteria in early log phase].", "content": "The bacteria harvested in the early log phase lyse when they are submitted to a pH above 10. The peptidoglycan is not degraded in these conditions. Thus, the authors used these properties to extract the peptidoglycan from several gram negative and gram positive bacteria.", "contents": "[Effect of pH on bacteria in early log phase]. The bacteria harvested in the early log phase lyse when they are submitted to a pH above 10. The peptidoglycan is not degraded in these conditions. Thus, the authors used these properties to extract the peptidoglycan from several gram negative and gram positive bacteria."}
{"id": "PMID:6161", "title": "Effect of timolol versus propranolol on hypertension and hemodynamics.", "content": "The effect of timolol versus propranolol on hypertension, hemodynamics, and plasms renin activity was evaluated in 20 men. After two weeks of placebo, 11 men received timolol 30 to 60 mg daily, and nine men received propranolol, 240 to 480 mg daily, for five weeks in a double-blind randomized study. The 20 men then received placebo again for two weeks. Right heart catheterization was performed in all 20 patients after two weeks of the first placebo and after five weeks of timolol or propranolol. Equipotent doses of timolol and propranolol were equally effective in significantly lowering supine and upright systolic and diastolic blood pressure and heart rate recorded on an outpatient basis. Equipotent doses of timolol and propranolol caused similar hemodynamic effects including similar significant depression of cardiac index. Equipotent doses of timolol and propranolol caused similar marked depression of plasma renin activity. The hypotensive action of timolol and of propranolol was unrelated to their effect on plasma renin activity.", "contents": "Effect of timolol versus propranolol on hypertension and hemodynamics. The effect of timolol versus propranolol on hypertension, hemodynamics, and plasms renin activity was evaluated in 20 men. After two weeks of placebo, 11 men received timolol 30 to 60 mg daily, and nine men received propranolol, 240 to 480 mg daily, for five weeks in a double-blind randomized study. The 20 men then received placebo again for two weeks. Right heart catheterization was performed in all 20 patients after two weeks of the first placebo and after five weeks of timolol or propranolol. Equipotent doses of timolol and propranolol were equally effective in significantly lowering supine and upright systolic and diastolic blood pressure and heart rate recorded on an outpatient basis. Equipotent doses of timolol and propranolol caused similar hemodynamic effects including similar significant depression of cardiac index. Equipotent doses of timolol and propranolol caused similar marked depression of plasma renin activity. The hypotensive action of timolol and of propranolol was unrelated to their effect on plasma renin activity."}
{"id": "PMID:6163", "title": "Determination of clomipramine and desmethyl-clomipramine in plasma or urine by the double-radioisotope derivative technique.", "content": "A double radioisotope derivative method was developed for the determination of clomipramine and desmethyl-clomipramine in plasma or urine. After addition of 14C-labeled clomipramine and desmethyl-clomipramine as internal standards and extractive isolation of both compounds, desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is separated from clomipramine by thin-layer chromatography and its radioactivity is measured. Clomipramine, extracted from the cilica gel, is reacted with trichloroethyl chloroformate. The urethane is saponified and decarboxylated. The resulting desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is purified by thin-layer chromatography and its radioactivity is measured. The sensitivity of the method is 15 mug/liter for clomipramine and 2 mug/liter for desmethyl-clomipramine. Its specificity was made sure by a cross-check with a gas chromatography-mass spectrometry technique.", "contents": "Determination of clomipramine and desmethyl-clomipramine in plasma or urine by the double-radioisotope derivative technique. A double radioisotope derivative method was developed for the determination of clomipramine and desmethyl-clomipramine in plasma or urine. After addition of 14C-labeled clomipramine and desmethyl-clomipramine as internal standards and extractive isolation of both compounds, desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is separated from clomipramine by thin-layer chromatography and its radioactivity is measured. Clomipramine, extracted from the cilica gel, is reacted with trichloroethyl chloroformate. The urethane is saponified and decarboxylated. The resulting desmethyl-clomipramine is acetylated with [3H]acetic anhydride. The [3H]acetamide is purified by thin-layer chromatography and its radioactivity is measured. The sensitivity of the method is 15 mug/liter for clomipramine and 2 mug/liter for desmethyl-clomipramine. Its specificity was made sure by a cross-check with a gas chromatography-mass spectrometry technique."}
{"id": "PMID:6164", "title": "Diazepam abuse: incidence, rapid screening, and confirming methods.", "content": "We studied 2500 patients suspected to be drug-overdose victims. Blood samples were quantitatively screened for the most commonly abused drugs, including diazepam. Of these, 61% had positive findings, including diazepam in about one of every four. A new rapid, simple, and quantitative gas-chromatographic method for simultaneous analysis of diazepam and sedatives (in two instruments) is described. A single extraction at low pH is used, preserving the balance of the sample to be used for confirming methods via ultraviolet spectrophotometry and thin-layer chromatography. Prevalance of other positive findings is also listed, and findings for diazepam are categorized by age.", "contents": "Diazepam abuse: incidence, rapid screening, and confirming methods. We studied 2500 patients suspected to be drug-overdose victims. Blood samples were quantitatively screened for the most commonly abused drugs, including diazepam. Of these, 61% had positive findings, including diazepam in about one of every four. A new rapid, simple, and quantitative gas-chromatographic method for simultaneous analysis of diazepam and sedatives (in two instruments) is described. A single extraction at low pH is used, preserving the balance of the sample to be used for confirming methods via ultraviolet spectrophotometry and thin-layer chromatography. Prevalance of other positive findings is also listed, and findings for diazepam are categorized by age."}
{"id": "PMID:6166", "title": "Determination of ionized calcium in serum that has been exposed to air.", "content": "We examined changes in ionized calcium concentration in serum after its exposure to air. Samples with total protein concentrations ranging from 50 to 90 g/liter were equilibrated with CO2 in nitrogen (5/95, by vol) or CO2 alone, to produce pH values of 7.0 to 8.0. Ionized calcium was then measured with an Orion flow-through electrode system. Curves relating pH and ionized calcium concentration had statistically identical slopes regardless of protein concentration. A factor was derived, based on pH change, for correcting values for ionized calcium in serum exposed to air, and its validity was confirmed by comparing corrected values for samples allowed to stand at ambient temperature (23 degrees C) without anaerobic precautions with values initially obtained on anaerobic aliquots of the same samples.", "contents": "Determination of ionized calcium in serum that has been exposed to air. We examined changes in ionized calcium concentration in serum after its exposure to air. Samples with total protein concentrations ranging from 50 to 90 g/liter were equilibrated with CO2 in nitrogen (5/95, by vol) or CO2 alone, to produce pH values of 7.0 to 8.0. Ionized calcium was then measured with an Orion flow-through electrode system. Curves relating pH and ionized calcium concentration had statistically identical slopes regardless of protein concentration. A factor was derived, based on pH change, for correcting values for ionized calcium in serum exposed to air, and its validity was confirmed by comparing corrected values for samples allowed to stand at ambient temperature (23 degrees C) without anaerobic precautions with values initially obtained on anaerobic aliquots of the same samples."}
{"id": "PMID:6167", "title": "In vitro changes in blood P50 and erythrocyte 2,3-diphosphoglycerate concentration.", "content": "We studied in vitro changes in P50 and erythrocyte 2,3-diphosphoglycerate concentration occurring in blood 2 to 8 h after venipuncture. When blood was incubated at 37 degrees C, significant decreases in P50 were observed at 2, 4, and 8 hr. Such a change was significantly less when blood was kept at 4 degrees C. The rate of decrease in P50 was not changed when pH was altered by adding either lactic acid or sodium bicarbonate to the blood before incubation at 37 degrees C for 2 h. The erythrocyte 2,3-diphosphoglycerate concentration of blood incubated at 37 degrees C did not change by 2 h, but had significantly decreased by 4 h. To avoid in vitro changes, we recommend that P50 be determined as soon as possible for blood sampling.", "contents": "In vitro changes in blood P50 and erythrocyte 2,3-diphosphoglycerate concentration. We studied in vitro changes in P50 and erythrocyte 2,3-diphosphoglycerate concentration occurring in blood 2 to 8 h after venipuncture. When blood was incubated at 37 degrees C, significant decreases in P50 were observed at 2, 4, and 8 hr. Such a change was significantly less when blood was kept at 4 degrees C. The rate of decrease in P50 was not changed when pH was altered by adding either lactic acid or sodium bicarbonate to the blood before incubation at 37 degrees C for 2 h. The erythrocyte 2,3-diphosphoglycerate concentration of blood incubated at 37 degrees C did not change by 2 h, but had significantly decreased by 4 h. To avoid in vitro changes, we recommend that P50 be determined as soon as possible for blood sampling."}
{"id": "PMID:6169", "title": "Alkaline phosphatase. I. Kinetics and inhibition by levamisole of purified isoenzymes from humans.", "content": "I studied the kinetics and sensitivity toward inhibition by levamisole and R 8231 of the most important human alkaline phosphatase isoenzymes. N-Ethylaminoethanol proved superior to the now widely used diethanolamine buffer, especially for the enzymes from the intestine and placenta, behaving as an uncompetitive activator. The optimum pH largely depends on the substrate concentration. The addition of Mg2+ has no effect on the activities. The meaning of Km-values for alkaline phosphatases is questioned. Isoenzymes from human liver, bone, kidney, and spleen are strongly inhibited by levamisole or R 8231 at concentrations that barely affect the enzymes from intestine or placenta. The inhibition is stereospecific, uncompetitive, and not changed by Mg2+. Inhibition is counteracted by increasing concentrations of N-ethylaminoethanol. The mechanism of inhibition is suggested to be formation of a complex with the phosphoenzyme.", "contents": "Alkaline phosphatase. I. Kinetics and inhibition by levamisole of purified isoenzymes from humans. I studied the kinetics and sensitivity toward inhibition by levamisole and R 8231 of the most important human alkaline phosphatase isoenzymes. N-Ethylaminoethanol proved superior to the now widely used diethanolamine buffer, especially for the enzymes from the intestine and placenta, behaving as an uncompetitive activator. The optimum pH largely depends on the substrate concentration. The addition of Mg2+ has no effect on the activities. The meaning of Km-values for alkaline phosphatases is questioned. Isoenzymes from human liver, bone, kidney, and spleen are strongly inhibited by levamisole or R 8231 at concentrations that barely affect the enzymes from intestine or placenta. The inhibition is stereospecific, uncompetitive, and not changed by Mg2+. Inhibition is counteracted by increasing concentrations of N-ethylaminoethanol. The mechanism of inhibition is suggested to be formation of a complex with the phosphoenzyme."}
{"id": "PMID:6170", "title": "Determination of erythrocyte folate by competitive protein binding assay preceded by extraction.", "content": "Determination of the concentration of erythrocyte folate by means of competitive protein binding assay critically depends on the extraction procedure applied. Results will be influenced by variable factors such as the in vitro age of the blood samples, the degree of hemolysis, the presence of ascorbic acid, and the pH during extraction and elimination of proteins. The radioassay is strongly influenced by the pH of the final reaction mixture, the method used to separate free and protein-bound molecules, and the molecular configuration of the folates present. Based on experimental results presented, I describe a method for the determination of erythrocyte folate.", "contents": "Determination of erythrocyte folate by competitive protein binding assay preceded by extraction. Determination of the concentration of erythrocyte folate by means of competitive protein binding assay critically depends on the extraction procedure applied. Results will be influenced by variable factors such as the in vitro age of the blood samples, the degree of hemolysis, the presence of ascorbic acid, and the pH during extraction and elimination of proteins. The radioassay is strongly influenced by the pH of the final reaction mixture, the method used to separate free and protein-bound molecules, and the molecular configuration of the folates present. Based on experimental results presented, I describe a method for the determination of erythrocyte folate."}
{"id": "PMID:6171", "title": "[Compared efficiency of mean corpuscular volume (MCV) and serum gamma-glutamyltransferase (gamma-GT) as screening tests for excess-ethanol drinkers (author's transl)].", "content": "53 percent of ethanol drinkers had, before detoxication, a gamma-GT higher than the upper limit of the reference interval at the 2.5 percent risk level (36 mU/ml). 44 percent had a mean corpuscular volume (MCV) higher than the limit (99.2 mum3). In alcoholics not previously \"weaned\" during a rest cure or in a hospital the proportion becomes 67 percent for gamma-GT but remains at 44 percent for MCV. gamma-GT thus seems a better test for the screening of an excessive ethanol intake than MCV, especially when the subject has not been previously weaned.", "contents": "[Compared efficiency of mean corpuscular volume (MCV) and serum gamma-glutamyltransferase (gamma-GT) as screening tests for excess-ethanol drinkers (author's transl)]. 53 percent of ethanol drinkers had, before detoxication, a gamma-GT higher than the upper limit of the reference interval at the 2.5 percent risk level (36 mU/ml). 44 percent had a mean corpuscular volume (MCV) higher than the limit (99.2 mum3). In alcoholics not previously \"weaned\" during a rest cure or in a hospital the proportion becomes 67 percent for gamma-GT but remains at 44 percent for MCV. gamma-GT thus seems a better test for the screening of an excessive ethanol intake than MCV, especially when the subject has not been previously weaned."}
{"id": "PMID:6173", "title": "[Separation of metanephrine and normetanephrine from urine for automated fluorimetric routine determination (author's transl)].", "content": "It is possible to separate metanephrine and normetanephrine from urine for the automated fluorimetric routine determination by means of a combination of liquid-liquid partition with ethylacetate and clean-up of the extract through Amberlite XAD-4. The differentiated fluorimetric determination is based on the oxidation with potassium hexacyanoferrate (III) in the presence of zinc ions and different pH values in an autoanalyzer. No quenching effects were observed. The recovery yields were in the range of 60%, the relative standard deviation being less than 10%.", "contents": "[Separation of metanephrine and normetanephrine from urine for automated fluorimetric routine determination (author's transl)]. It is possible to separate metanephrine and normetanephrine from urine for the automated fluorimetric routine determination by means of a combination of liquid-liquid partition with ethylacetate and clean-up of the extract through Amberlite XAD-4. The differentiated fluorimetric determination is based on the oxidation with potassium hexacyanoferrate (III) in the presence of zinc ions and different pH values in an autoanalyzer. No quenching effects were observed. The recovery yields were in the range of 60%, the relative standard deviation being less than 10%."}
{"id": "PMID:6174", "title": "Improved radioiodination of glucagon with the lactoperoxidase method. Influence of pH on iodine substitution.", "content": "To produce a 125I-labelled glucagon suitable for radioligand assays, we studied the influence of variations in the lactoperoxidase iodination method. Both the degree of iodine substitution and the formation of monoiodo- or diiodo-tyrosines were pH dependent. The substitution increased and the diiodo-/monoiodotyrosine ratio decreased when pH increased. These two factors affected the immunoreactivity of the iodoglucagon relatively independently of each other. It was found that iodination at pH 10.0 with an average of 0.3 gatom I/mol glucagon resulted in 125I-labelled glucagon with higher immunoreactivity and stability than that produced at the conventional pH 7.5 and 8.5.", "contents": "Improved radioiodination of glucagon with the lactoperoxidase method. Influence of pH on iodine substitution. To produce a 125I-labelled glucagon suitable for radioligand assays, we studied the influence of variations in the lactoperoxidase iodination method. Both the degree of iodine substitution and the formation of monoiodo- or diiodo-tyrosines were pH dependent. The substitution increased and the diiodo-/monoiodotyrosine ratio decreased when pH increased. These two factors affected the immunoreactivity of the iodoglucagon relatively independently of each other. It was found that iodination at pH 10.0 with an average of 0.3 gatom I/mol glucagon resulted in 125I-labelled glucagon with higher immunoreactivity and stability than that produced at the conventional pH 7.5 and 8.5."}
{"id": "PMID:6175", "title": "Arylamidases in normal and diseased human muscle.", "content": "Human skeletal muscle homogenates were found to contain enzymes that catalyze the hydrolysis of beta-naphthylamides of leucine, arginine and lysine, known substrates for neutral and basic arylamidases. They also contained a trace of activity towards alpha-aspartyl-beta-naphthylamide. The muscle arylamidases were found to be inhibited by p-chloromercuribenzoate, Hg2+ and puromycin. Leucyl, arginyl and lysysl arylamidases were slightly activated by cobalt ions. When compared to controls, no significant differences in muscle arylamidase activities were observed in patients with muscular dystrophies and certain denervating diseases.", "contents": "Arylamidases in normal and diseased human muscle. Human skeletal muscle homogenates were found to contain enzymes that catalyze the hydrolysis of beta-naphthylamides of leucine, arginine and lysine, known substrates for neutral and basic arylamidases. They also contained a trace of activity towards alpha-aspartyl-beta-naphthylamide. The muscle arylamidases were found to be inhibited by p-chloromercuribenzoate, Hg2+ and puromycin. Leucyl, arginyl and lysysl arylamidases were slightly activated by cobalt ions. When compared to controls, no significant differences in muscle arylamidase activities were observed in patients with muscular dystrophies and certain denervating diseases."}
{"id": "PMID:6178", "title": "Surgical aspects of infertility.", "content": "These surgical procedures that have been used in the management of male infertility have recently been subjected to critical review. In a recent study (Getzoff, 1973) designed to summarise the experience of 150 urologists in the surgical treatment of male infertility, several valuable viewpoints were revealed. 1. There is a need for establishing criteria for labelling an operation as a 'success'. In this group, 42 per cent defined a successful operation as the postoperative appearance of a normal semen analysis in the azoospermic or oligospermic man regardless of whether his wife fails to conceive. Thirty per cent were more stringent and required that the wife become pregnant and carry to term a normal viable infant. 2. The prerequisites for selecting suitable candidates for surgery were apparent. 3. The significance of establishing basic effective operative techniques is self-evident. 4. The importance of emphasising the limitations of the surgical management of impaired fertility is stressed.", "contents": "Surgical aspects of infertility. These surgical procedures that have been used in the management of male infertility have recently been subjected to critical review. In a recent study (Getzoff, 1973) designed to summarise the experience of 150 urologists in the surgical treatment of male infertility, several valuable viewpoints were revealed. 1. There is a need for establishing criteria for labelling an operation as a 'success'. In this group, 42 per cent defined a successful operation as the postoperative appearance of a normal semen analysis in the azoospermic or oligospermic man regardless of whether his wife fails to conceive. Thirty per cent were more stringent and required that the wife become pregnant and carry to term a normal viable infant. 2. The prerequisites for selecting suitable candidates for surgery were apparent. 3. The significance of establishing basic effective operative techniques is self-evident. 4. The importance of emphasising the limitations of the surgical management of impaired fertility is stressed."}
{"id": "PMID:6179", "title": "Effects of cardioselective beta adrenoceptor blockade on specific airways resistance in normal subjects and in patients with bronchial asthma.", "content": "The effects of single oral doses of the cardioselective beta adrenoceptor blocking drugs, metoprolol and tolamolol, on specific airways resistance (SRaw) were compared with those of propranolol and practolol in 6 healthy volunteers and in 12 patients with bronchial asthma. Whole-body plethysmography was used to measure SRaw and the blocking potency of different antagonists assessed by the degree of inhibition of tachycardia due to exercise on a treadmill. The changes correlated with plasma drug levels. Propranolol and practolol were measured fluorometrically and metoprolol by electron-capture gas-liquid chromatography. In normal subjects, about 30% reduction in exercise-induced tachycardia resulted from single doses of 80 mg propranolol (plasma levels, 50.3, SD, 29.5 to 60.8, SD, 26 ng/ml), 250 mg practolol (plasma levels, 1.05, SD, 0.32 to 1.10, SD, 0.55 mug/ml), 100 mg metoprolol (plasma levels, 137, SD, 111 to 152, SD, 100 ng/ml), and 100 mg tolamolol. In patients, these doses of the drugs produced significant increases in SRaw. These increases were greater than those after placebo but significantly so only during the peak effect 1 hr after propranolol. Compared with changes after placebo, significant effects on SRaw were also found in 3 patients given 200 mg of tolamolol. None of the drugs had a significant effect on SRaw in normal subjects. It is concluded that metoprolol, practolol, and tolamolol may impair ventilatory function in asthmatics less than propranolol and that at high doses this difference may not be demonstrable.", "contents": "Effects of cardioselective beta adrenoceptor blockade on specific airways resistance in normal subjects and in patients with bronchial asthma. The effects of single oral doses of the cardioselective beta adrenoceptor blocking drugs, metoprolol and tolamolol, on specific airways resistance (SRaw) were compared with those of propranolol and practolol in 6 healthy volunteers and in 12 patients with bronchial asthma. Whole-body plethysmography was used to measure SRaw and the blocking potency of different antagonists assessed by the degree of inhibition of tachycardia due to exercise on a treadmill. The changes correlated with plasma drug levels. Propranolol and practolol were measured fluorometrically and metoprolol by electron-capture gas-liquid chromatography. In normal subjects, about 30% reduction in exercise-induced tachycardia resulted from single doses of 80 mg propranolol (plasma levels, 50.3, SD, 29.5 to 60.8, SD, 26 ng/ml), 250 mg practolol (plasma levels, 1.05, SD, 0.32 to 1.10, SD, 0.55 mug/ml), 100 mg metoprolol (plasma levels, 137, SD, 111 to 152, SD, 100 ng/ml), and 100 mg tolamolol. In patients, these doses of the drugs produced significant increases in SRaw. These increases were greater than those after placebo but significantly so only during the peak effect 1 hr after propranolol. Compared with changes after placebo, significant effects on SRaw were also found in 3 patients given 200 mg of tolamolol. None of the drugs had a significant effect on SRaw in normal subjects. It is concluded that metoprolol, practolol, and tolamolol may impair ventilatory function in asthmatics less than propranolol and that at high doses this difference may not be demonstrable."}
{"id": "PMID:6180", "title": "Sleep laboratory studies of flurazepam: a model for evaluating hypnotic drugs.", "content": "The results from six separate evaluations of flurazepam 30 mg in the sleep laboratory were combined to determine the effectiveness of the drug in inducing and maintaining sleep and its effects on sleep stages in a large sample of insomniac subjects. The combined studies provide a model from which a detailed profile of the effects of a hypnotic drug over short-, intermediate-, and long-term conditions can be thoroughly evaluated. Although sleep was significantly improved on the first night of flurazepam administration, peak effectiveness of the drug did not result until the second and third consecutive drug nights. Flurazepam continued to be effective in inducing and maintaining sleep with intermediate-and long-term drug use with only a slight loss of effectiveness with long-term use. Sleep was also significantly improved on the first and second nights of drug withdrawal. Carryover effectiveness of active metabolites of flurazepam from one drug night to the next drug night and to withdrawl nights is discussed. The clinical implications are discussed with regard to the time of peak effectiveness of the drug, dosage recommendations and schedule, minimizing possible effects of the drug on daytime performance, and the rationale and method for using drug holidays in the treatment regimen. With this comprehensive profile of the drug's actions, the physician is able to more rationally and effectively utilize the drug in treating the insomniac patient. With short-term administration, flurazepam produced a slight decrease in rapid eye movement (REM) sleep and an increase in REM latency. These effects were much more pronounced with intermediate-term drug administration, again possibly due to the accumulation of active metabolites. After withdrawal there was no rebound in REM sleep. Stages 3 and 4 sleep decreased progressively through short and intermediate drug administration. With initial withdrawal, there was a slight recovery in both sleep stages.", "contents": "Sleep laboratory studies of flurazepam: a model for evaluating hypnotic drugs. The results from six separate evaluations of flurazepam 30 mg in the sleep laboratory were combined to determine the effectiveness of the drug in inducing and maintaining sleep and its effects on sleep stages in a large sample of insomniac subjects. The combined studies provide a model from which a detailed profile of the effects of a hypnotic drug over short-, intermediate-, and long-term conditions can be thoroughly evaluated. Although sleep was significantly improved on the first night of flurazepam administration, peak effectiveness of the drug did not result until the second and third consecutive drug nights. Flurazepam continued to be effective in inducing and maintaining sleep with intermediate-and long-term drug use with only a slight loss of effectiveness with long-term use. Sleep was also significantly improved on the first and second nights of drug withdrawal. Carryover effectiveness of active metabolites of flurazepam from one drug night to the next drug night and to withdrawl nights is discussed. The clinical implications are discussed with regard to the time of peak effectiveness of the drug, dosage recommendations and schedule, minimizing possible effects of the drug on daytime performance, and the rationale and method for using drug holidays in the treatment regimen. With this comprehensive profile of the drug's actions, the physician is able to more rationally and effectively utilize the drug in treating the insomniac patient. With short-term administration, flurazepam produced a slight decrease in rapid eye movement (REM) sleep and an increase in REM latency. These effects were much more pronounced with intermediate-term drug administration, again possibly due to the accumulation of active metabolites. After withdrawal there was no rebound in REM sleep. Stages 3 and 4 sleep decreased progressively through short and intermediate drug administration. With initial withdrawal, there was a slight recovery in both sleep stages."}
{"id": "PMID:6181", "title": "Antibacterial activity and pharmacokinetics of bacampicillin and ampicillin.", "content": "Single equimolar oral doses of bacampicillin and ampicillin were given to 9 healthy subjects on a crossover randomized basis. Data were interpreted in terms of a 3-compartment pharmacokinetic open model. Intestinal absorption of bacampicillin was found to be faster and more complete than that of ampicillin, yielding an increase in bioavailability of 30% to 40% as measured by the area under serum levels curve, the urinary excretion and absorption rate constants. After the administration of bacampicillin, much higher and sharper peaks were achieved in the serum and in the \"tissue\" water than after the administration of ampicillin. The maximum bactericidal dilution (MBD) of the serum samples taken 1 hr after the administration of the antibiotics against 10 strains of Diplococcus pneumoniae was higher following bacampicillin (p less than 0.01), as was the MBD of the 0 to 2 hr urine specimens against 10 strains of Escherichia coli. Further clinical trials are required to accurately assess the possible greater therapeutic effectiveness of bacampicillin than of ampicillin.", "contents": "Antibacterial activity and pharmacokinetics of bacampicillin and ampicillin. Single equimolar oral doses of bacampicillin and ampicillin were given to 9 healthy subjects on a crossover randomized basis. Data were interpreted in terms of a 3-compartment pharmacokinetic open model. Intestinal absorption of bacampicillin was found to be faster and more complete than that of ampicillin, yielding an increase in bioavailability of 30% to 40% as measured by the area under serum levels curve, the urinary excretion and absorption rate constants. After the administration of bacampicillin, much higher and sharper peaks were achieved in the serum and in the \"tissue\" water than after the administration of ampicillin. The maximum bactericidal dilution (MBD) of the serum samples taken 1 hr after the administration of the antibiotics against 10 strains of Diplococcus pneumoniae was higher following bacampicillin (p less than 0.01), as was the MBD of the 0 to 2 hr urine specimens against 10 strains of Escherichia coli. Further clinical trials are required to accurately assess the possible greater therapeutic effectiveness of bacampicillin than of ampicillin."}
{"id": "PMID:6182", "title": "Effect of phenobarbitone on plasma lipids in normal subjects.", "content": "1. Phenobarbitone in a dose of 180 mg daily was administered to ten normal subjects for 3 weeks. There was a significant increase in total plasma cholesterol, plasma low-density-lipoprotein cholesterol, plasma low-density-lipoprotein (LDL) triglycerides and plasma LDL protein. The increase in plasma LDL cholesterol accounted for the increase in total plasma cholesterol. There was a significant reduction in the ratio of LDL cholesterol to LDL protein. 2. No significant changes were observed in total plasma triglycerides, plasma very-low-density-lipoprotein (VLDL) triglycerides, plasma VLDL cholesterol or plasma VLDL protein. 3. Evidence that drug-metabolizing enzymes were induced by phenobarbitone was provided by an increase in antipyrine clearance. No relationship was observed between changes in plasma cholesterol and changes in antipyrine clearance. Serum gamma-glutamyl transpeptidase was also increased after phenobarbitone administration, the increase being unrelated to changes in antipyrine clearance or plasma cholesterol.", "contents": "Effect of phenobarbitone on plasma lipids in normal subjects. 1. Phenobarbitone in a dose of 180 mg daily was administered to ten normal subjects for 3 weeks. There was a significant increase in total plasma cholesterol, plasma low-density-lipoprotein cholesterol, plasma low-density-lipoprotein (LDL) triglycerides and plasma LDL protein. The increase in plasma LDL cholesterol accounted for the increase in total plasma cholesterol. There was a significant reduction in the ratio of LDL cholesterol to LDL protein. 2. No significant changes were observed in total plasma triglycerides, plasma very-low-density-lipoprotein (VLDL) triglycerides, plasma VLDL cholesterol or plasma VLDL protein. 3. Evidence that drug-metabolizing enzymes were induced by phenobarbitone was provided by an increase in antipyrine clearance. No relationship was observed between changes in plasma cholesterol and changes in antipyrine clearance. Serum gamma-glutamyl transpeptidase was also increased after phenobarbitone administration, the increase being unrelated to changes in antipyrine clearance or plasma cholesterol."}
{"id": "PMID:6183", "title": "Analytical subcellular fractionation studies on rat liver and on isolated jejunal enterocytes with special reference to the separation of lysosomes, peroxisomes and mitochondria.", "content": "1. Enterocytes were isolated from rat jejunum and characterized morphologically. 2. Attempts to separate the enterocyte subcellular organelles, characterized by their marker enzymes, with isopycnic centrifugation were unsuccessful but good separation of peroxisomes, lysosomes and mitochondria was achieved by sedimentation through a shallow sucrose density gradient with a super-imposed inverse gradient of low-molecular-weight dextran. 3. The properties and enzyme activities of the principal subcellular organelles in rat liver cells and enterocytes were compared.", "contents": "Analytical subcellular fractionation studies on rat liver and on isolated jejunal enterocytes with special reference to the separation of lysosomes, peroxisomes and mitochondria. 1. Enterocytes were isolated from rat jejunum and characterized morphologically. 2. Attempts to separate the enterocyte subcellular organelles, characterized by their marker enzymes, with isopycnic centrifugation were unsuccessful but good separation of peroxisomes, lysosomes and mitochondria was achieved by sedimentation through a shallow sucrose density gradient with a super-imposed inverse gradient of low-molecular-weight dextran. 3. The properties and enzyme activities of the principal subcellular organelles in rat liver cells and enterocytes were compared."}
{"id": "PMID:6184", "title": "The ventilatory response in severe metabolic acidosis.", "content": "1. The ventilatory response to severe metabolic acidosis was studied by measuring arterial blood carbon dioxide tension and pH in sixty-seven patients with blood pH less than 7-10, none of whom had hypercapnia, pulmonary oedema, or chronic pulmonary insufficiency. The results were compared with those previously found in patients with uncomplicated diabetic ketoacidosis. 2. By that comparison, fifty-two of the sixty-seven patients with blood pH less than 7-10 were judged to have \"appropriate hypocapnia\", and fifteen had \"submaximal hypocapnia\". Thirteen of the latter fifteen had circulatory failture and/or acute hypoxia, and seven of nine in whom it was measured had plasma lactate greater than 9 mmol/1. 3. Hyperventilation was therefore usually well sustained in these patients with severe metabolic acidosis, except in most of those with acute tissue hypoxia. The latter may have had insufficient time to achieve maximum hyperventilation in response to their acidosis, or perhaps their submaximal hypercapnia presaged imminent failure of the hyperventilatory response.", "contents": "The ventilatory response in severe metabolic acidosis. 1. The ventilatory response to severe metabolic acidosis was studied by measuring arterial blood carbon dioxide tension and pH in sixty-seven patients with blood pH less than 7-10, none of whom had hypercapnia, pulmonary oedema, or chronic pulmonary insufficiency. The results were compared with those previously found in patients with uncomplicated diabetic ketoacidosis. 2. By that comparison, fifty-two of the sixty-seven patients with blood pH less than 7-10 were judged to have \"appropriate hypocapnia\", and fifteen had \"submaximal hypocapnia\". Thirteen of the latter fifteen had circulatory failture and/or acute hypoxia, and seven of nine in whom it was measured had plasma lactate greater than 9 mmol/1. 3. Hyperventilation was therefore usually well sustained in these patients with severe metabolic acidosis, except in most of those with acute tissue hypoxia. The latter may have had insufficient time to achieve maximum hyperventilation in response to their acidosis, or perhaps their submaximal hypercapnia presaged imminent failure of the hyperventilatory response."}
{"id": "PMID:6185", "title": "Some properties of human platelet monoamine oxidase in iron-deficiency anaemia.", "content": "1. Monoamine oxidase activity in platelets prepared from the blood of patients with iron-deficiency anaemia was significantly lowered when compared with that in platelets from normal subjects. 2. The Km values of the platelet enzyme for the substrates dopamine, 5-hydroxytryptamine, phenylethylamine and kynuramine were similar for the platelet enzyme from iron-deficient and normal groups. 3. Heat-in-activation studies showed that the platelet monoamine oxidase from iron-deficient subjects was more labile to this treatment, when compared with the platelet enzyme from normal subjects. 4. The sensitivity of platelet monoamine oxidase to the inhibitors, clorgyline and deprenil, was increased in iron-deficiency anaemia. 5. Binding studies with the 14C-binding irreversible monoamine oxidase inhibitor, deprenil, showed that the amount of enzyme capable of binding this inhibitor was lowered by 48% in platelets from iron-deficient patients when compared with platelets from normal subjects. 6. The results show that there is a lowered amount of active enzyme in platelets from iron-deficient subjects. It is suggested that iron is necessary either for the synthesis of monoamine oxidase apoenzyme or is a cofactor for an enzyme which attaches flavin-adenine dinucleotide covalently to the monoamine oxidase apoenzyme.", "contents": "Some properties of human platelet monoamine oxidase in iron-deficiency anaemia. 1. Monoamine oxidase activity in platelets prepared from the blood of patients with iron-deficiency anaemia was significantly lowered when compared with that in platelets from normal subjects. 2. The Km values of the platelet enzyme for the substrates dopamine, 5-hydroxytryptamine, phenylethylamine and kynuramine were similar for the platelet enzyme from iron-deficient and normal groups. 3. Heat-in-activation studies showed that the platelet monoamine oxidase from iron-deficient subjects was more labile to this treatment, when compared with the platelet enzyme from normal subjects. 4. The sensitivity of platelet monoamine oxidase to the inhibitors, clorgyline and deprenil, was increased in iron-deficiency anaemia. 5. Binding studies with the 14C-binding irreversible monoamine oxidase inhibitor, deprenil, showed that the amount of enzyme capable of binding this inhibitor was lowered by 48% in platelets from iron-deficient patients when compared with platelets from normal subjects. 6. The results show that there is a lowered amount of active enzyme in platelets from iron-deficient subjects. It is suggested that iron is necessary either for the synthesis of monoamine oxidase apoenzyme or is a cofactor for an enzyme which attaches flavin-adenine dinucleotide covalently to the monoamine oxidase apoenzyme."}
{"id": "PMID:6188", "title": "Central nervous system salicylate.", "content": "The poor correlation between clinical salicylate toxicity and serum blood levels is reapproached in light of recent evidence linking clinical severity with initial volume of distribution (Vd). It is recognized that two variables alter salicylate Vd in such manner that serum salicylate levels are misleading (thus, the change in Vd is not detected by present methods). These variables are serum protein binding and the pH-dependent ionized/un-ionized ratio in the unbound salicylate fraction. Measurements of salicylate concentration in the cerebro spinal fluid (CSF) would  circumvent these variables, but would be clinically impractical. Thus, an alternative is sought to the inexact  total serum salicylate levels and the impractical CSF salicylate  levels for assessment of the severity of salicylate poisoning. This study indicates that, in dogs, serum unbound salicylate  levels closely reflect CSF salicylate levels, even as a decrease in serum protein binding  is in progress. However, serum unbound salicylate concentration does not reflect CSF salicylate concentration as a decrease  in serum pH is elicited (CSF salicylate actually increased as serum unbound salicylate decreased). On the other  hand, serum unbound salicylate measurement would seem preferable to total serum salicylate measurements now used in that the total value decreased markedly as either protein binding change or acidosis produced a change in distribution and the resultant increase in CSF salicylate.", "contents": "Central nervous system salicylate. The poor correlation between clinical salicylate toxicity and serum blood levels is reapproached in light of recent evidence linking clinical severity with initial volume of distribution (Vd). It is recognized that two variables alter salicylate Vd in such manner that serum salicylate levels are misleading (thus, the change in Vd is not detected by present methods). These variables are serum protein binding and the pH-dependent ionized/un-ionized ratio in the unbound salicylate fraction. Measurements of salicylate concentration in the cerebro spinal fluid (CSF) would  circumvent these variables, but would be clinically impractical. Thus, an alternative is sought to the inexact  total serum salicylate levels and the impractical CSF salicylate  levels for assessment of the severity of salicylate poisoning. This study indicates that, in dogs, serum unbound salicylate  levels closely reflect CSF salicylate levels, even as a decrease in serum protein binding  is in progress. However, serum unbound salicylate concentration does not reflect CSF salicylate concentration as a decrease  in serum pH is elicited (CSF salicylate actually increased as serum unbound salicylate decreased). On the other  hand, serum unbound salicylate measurement would seem preferable to total serum salicylate measurements now used in that the total value decreased markedly as either protein binding change or acidosis produced a change in distribution and the resultant increase in CSF salicylate."}
{"id": "PMID:6221", "title": "Polypharmacy in the psychiatric treatment of elderly hospitalized patients: a survey of 12 Veterans Administration Hospitals.", "content": "Polypharmacy with psychoactive drugs was surveyed in 1276 elderly psychiatric patients from 12 Veterans Administration hospitals. One out of every six patients received two or more psychoactive agents. No specific combination of drugs was overly popular. The most frequently administered combinations, thioridazine plus phenobarbital and chlorpromazine plus phenobarbital, were administered to only 13 patients each (1% of the sample). The large majority of the combinations involved antipsychotic agents. One antipsychotic drug, thioridazine, was a component of nearly one-third of the combinations. The most frequent pairings were an antipsychotic drug plus and antidepressant, two antipsychotic drugs, and an antipsychotic drug plus an antianxiety agent or sedative-hypnotic. The use of polypharmacy was significantly related to patient age. One out of every four patients 60 to 65 years of age received two or more psychoactive drugs compared to only one out of eight over 75 years of age. The implications of these findings for treatment and research are discussed.", "contents": "Polypharmacy in the psychiatric treatment of elderly hospitalized patients: a survey of 12 Veterans Administration Hospitals. Polypharmacy with psychoactive drugs was surveyed in 1276 elderly psychiatric patients from 12 Veterans Administration hospitals. One out of every six patients received two or more psychoactive agents. No specific combination of drugs was overly popular. The most frequently administered combinations, thioridazine plus phenobarbital and chlorpromazine plus phenobarbital, were administered to only 13 patients each (1% of the sample). The large majority of the combinations involved antipsychotic agents. One antipsychotic drug, thioridazine, was a component of nearly one-third of the combinations. The most frequent pairings were an antipsychotic drug plus and antidepressant, two antipsychotic drugs, and an antipsychotic drug plus an antianxiety agent or sedative-hypnotic. The use of polypharmacy was significantly related to patient age. One out of every four patients 60 to 65 years of age received two or more psychoactive drugs compared to only one out of eight over 75 years of age. The implications of these findings for treatment and research are discussed."}
{"id": "PMID:6222", "title": "Mixed function oxidase activity in a marsupial. The quokka (Seton;x brachyurus).", "content": "Components of the cytochrome P-450 pathway and rates of oxidative hepatic metabolism of the substrates, ethylmorphine, 3,4-benzpyrene, and aniline, have been investigated in a marsupial (the quokka, Setonix brachyurus) and compared with those of the rat. In general the quokka had lower rates of drug metabolism and higher KM values than those found in the rat. Sex differences in Vmax and KM were also found for the quokka. These species and sex differences in oxidative drug metabolism did not correlate with measured concentrations of cytochromes P-450 or b5 or with NADPH-cytochrome c reductase activities, and have been attributed to differences in both KM and Vmax values.", "contents": "Mixed function oxidase activity in a marsupial. The quokka (Seton;x brachyurus). Components of the cytochrome P-450 pathway and rates of oxidative hepatic metabolism of the substrates, ethylmorphine, 3,4-benzpyrene, and aniline, have been investigated in a marsupial (the quokka, Setonix brachyurus) and compared with those of the rat. In general the quokka had lower rates of drug metabolism and higher KM values than those found in the rat. Sex differences in Vmax and KM were also found for the quokka. These species and sex differences in oxidative drug metabolism did not correlate with measured concentrations of cytochromes P-450 or b5 or with NADPH-cytochrome c reductase activities, and have been attributed to differences in both KM and Vmax values."}
{"id": "PMID:6223", "title": "A comprehensive study of in vitro drug metabolism in several laboratory species.", "content": "A shortage of rhesus monkeys for use in drug toxicity studies has made it necessary to search for a potential replacement species in the event that one should be needed in the near future. To this end, 14 parameters of drug metabolism in hepatic microsomal and soluble fractions were examined in preparations from adult male and female rhesus monkeys, squirrel monkeys, Hanford miniature pigs, common tree shrews, and Sprague-Dawley rats. Model substrates were utilized and comparisons were made on a quantitative basis. All species tested demonstrated activity in all but one test assay and all showed some similarity to the rhesus. None of the species, however, was totally comparable to the rhesus in drug-metabolizing ability. The squirrel monkey showed the least similarity to the rhesus and the miniature pig was the most similar. With the exception of the expected differences in the rat, the tree shrew demonstrated the only sex difference in drug metabolism, the enzyme activities of females being higher than the male in several pathways. The data suggest that any of the four species tested could be a suitable replacement for the rhesus in studies of drug metabolism in vitro.", "contents": "A comprehensive study of in vitro drug metabolism in several laboratory species. A shortage of rhesus monkeys for use in drug toxicity studies has made it necessary to search for a potential replacement species in the event that one should be needed in the near future. To this end, 14 parameters of drug metabolism in hepatic microsomal and soluble fractions were examined in preparations from adult male and female rhesus monkeys, squirrel monkeys, Hanford miniature pigs, common tree shrews, and Sprague-Dawley rats. Model substrates were utilized and comparisons were made on a quantitative basis. All species tested demonstrated activity in all but one test assay and all showed some similarity to the rhesus. None of the species, however, was totally comparable to the rhesus in drug-metabolizing ability. The squirrel monkey showed the least similarity to the rhesus and the miniature pig was the most similar. With the exception of the expected differences in the rat, the tree shrew demonstrated the only sex difference in drug metabolism, the enzyme activities of females being higher than the male in several pathways. The data suggest that any of the four species tested could be a suitable replacement for the rhesus in studies of drug metabolism in vitro."}
{"id": "PMID:6224", "title": "Biochemical properties of some microsomal xenobiotic-metabolizing enzymes in rabbit small intestine.", "content": "Comparison of xenobiotic-metabolizing enzymes in rabbit small intestinal and hepatic microsomal fractions showed mainly quantitative differences; most of the activities were two to seven times higher in liver than in intestine. However, UDP-glucuronyltransferase activity was higher in intestine than in liver. The apparent absence of benzene hydroxylase in small intestine was the only qualitative difference noticed. Aniline hydroxylase, aminopyrine N-demethylase, and aryl hydrocarbon dydroxylase were characterized in intestinal microsomes and compared to those of liver. Distribution of these enzymes along the entire length of small intestine showed that maximum activities of the enzymes were present in the proximal 60 cm of the intestine. All the enzymes in both tissues required NADPH and O2 for maximum activity and were inhibited by cytochrome c, SKF 525-A, and CO. The in vitro addition of drug substrates to microsomal fractions of both tissues produced typical type I and type II binding spectra. Comparison of the relationships between activities and pH, duration of incubation, and substrate and protein concentration suggested that the rabbit intestinal and hepatic xenobiotic-metabolizing enzymes studied have similar characteristics.", "contents": "Biochemical properties of some microsomal xenobiotic-metabolizing enzymes in rabbit small intestine. Comparison of xenobiotic-metabolizing enzymes in rabbit small intestinal and hepatic microsomal fractions showed mainly quantitative differences; most of the activities were two to seven times higher in liver than in intestine. However, UDP-glucuronyltransferase activity was higher in intestine than in liver. The apparent absence of benzene hydroxylase in small intestine was the only qualitative difference noticed. Aniline hydroxylase, aminopyrine N-demethylase, and aryl hydrocarbon dydroxylase were characterized in intestinal microsomes and compared to those of liver. Distribution of these enzymes along the entire length of small intestine showed that maximum activities of the enzymes were present in the proximal 60 cm of the intestine. All the enzymes in both tissues required NADPH and O2 for maximum activity and were inhibited by cytochrome c, SKF 525-A, and CO. The in vitro addition of drug substrates to microsomal fractions of both tissues produced typical type I and type II binding spectra. Comparison of the relationships between activities and pH, duration of incubation, and substrate and protein concentration suggested that the rabbit intestinal and hepatic xenobiotic-metabolizing enzymes studied have similar characteristics."}
{"id": "PMID:6225", "title": "Comparison of hepatic microsomal drug-metabolizing systems from rats fed crude and purified diets.", "content": "Hepatic microsomes from rats fed a crude or a purified diet were compared by measureing their contents of protein, cytochrome P-450, and cytochrome b5, their rates of activity of NADPH- and NADH-cytochrome c reductases, NADPH-cytochrome P-450 reductase, NADPH oxidase, lipid peroxidase, ethylmorphine N-demethylase, aniline hydroxylase, benzpyrene hydroxylase, and their substrate-binding spectra (ethylmorphine, hexobarbital, aniline, and ethyl isoyanide). With the exception of lipid peroxidase activity, which was much higher in microsomes from animals fed the crude diet, little or no consistent diet-related differences in these measurements were observed over a 4-week experimental period, nor were results significantly less variable with one or the other diet. No consistent significant differences were observed with two strains of rats. The lower lipid peroxidase activity seen with the purified diet appeared to be due to the high vitamin E intake when that diet was employed; rats fed the crude diet and an oral supplement of alpha-tocopherol yielded microsomes with low lipid peroxidase activities similar to those seen in microsomes from rats fed the purified diet. A gradual temporal increase in benzpyrene hydroxylase activity was observed with both diets. This was interpreted to be due to environment inducing agents other than those present in the diet.", "contents": "Comparison of hepatic microsomal drug-metabolizing systems from rats fed crude and purified diets. Hepatic microsomes from rats fed a crude or a purified diet were compared by measureing their contents of protein, cytochrome P-450, and cytochrome b5, their rates of activity of NADPH- and NADH-cytochrome c reductases, NADPH-cytochrome P-450 reductase, NADPH oxidase, lipid peroxidase, ethylmorphine N-demethylase, aniline hydroxylase, benzpyrene hydroxylase, and their substrate-binding spectra (ethylmorphine, hexobarbital, aniline, and ethyl isoyanide). With the exception of lipid peroxidase activity, which was much higher in microsomes from animals fed the crude diet, little or no consistent diet-related differences in these measurements were observed over a 4-week experimental period, nor were results significantly less variable with one or the other diet. No consistent significant differences were observed with two strains of rats. The lower lipid peroxidase activity seen with the purified diet appeared to be due to the high vitamin E intake when that diet was employed; rats fed the crude diet and an oral supplement of alpha-tocopherol yielded microsomes with low lipid peroxidase activities similar to those seen in microsomes from rats fed the purified diet. A gradual temporal increase in benzpyrene hydroxylase activity was observed with both diets. This was interpreted to be due to environment inducing agents other than those present in the diet."}
{"id": "PMID:6226", "title": "Depression of the hepatic cytochrome P-450 mono-oxygenase system by administered tilorone (2,7-bis(2-(diethylamino)ethoxy)fluoren-9-one dihydrochloride).", "content": "The oral administration of the antiviral agent, tilorone-HCl (50 mg/day for 4 days) to rats caused losses of hepatic microsomal ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase and aniline hydroxylase activities of 50, 44 and 22%, respectively. Microsomal levels of cytochrome P-450 and NADPH-cytochrome c reductase were lowered by 40 and 20% respectively, but levels of cytochrome b5 and NADH-cytochrome c reductase remained unchanged. After a single oral dose of tilorone-HCl (50 mg/kg) a loss of 38% of the microsomal cytochrome P-450 and 25% of the ethylmorphine N-demethylase activity was observed within 24 hr; recovery was complete within 8 to 10 days. Hexobarbital sleeping times and blood levels were elevated after tilorone administration (20 or 50 mg/kg/day for 4 days). In vitro, tilorone-HCl showed no inhibitory effect on microsomal drug metabolism nod did it affect the cytochrome P-450 content of the microsomes. The rate of incorporation of  delta-amino(3H)levulinic acid into cytochrome P-450 was not affected by tilorone-HCl.", "contents": "Depression of the hepatic cytochrome P-450 mono-oxygenase system by administered tilorone (2,7-bis(2-(diethylamino)ethoxy)fluoren-9-one dihydrochloride). The oral administration of the antiviral agent, tilorone-HCl (50 mg/day for 4 days) to rats caused losses of hepatic microsomal ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase and aniline hydroxylase activities of 50, 44 and 22%, respectively. Microsomal levels of cytochrome P-450 and NADPH-cytochrome c reductase were lowered by 40 and 20% respectively, but levels of cytochrome b5 and NADH-cytochrome c reductase remained unchanged. After a single oral dose of tilorone-HCl (50 mg/kg) a loss of 38% of the microsomal cytochrome P-450 and 25% of the ethylmorphine N-demethylase activity was observed within 24 hr; recovery was complete within 8 to 10 days. Hexobarbital sleeping times and blood levels were elevated after tilorone administration (20 or 50 mg/kg/day for 4 days). In vitro, tilorone-HCl showed no inhibitory effect on microsomal drug metabolism nod did it affect the cytochrome P-450 content of the microsomes. The rate of incorporation of  delta-amino(3H)levulinic acid into cytochrome P-450 was not affected by tilorone-HCl."}
{"id": "PMID:6228", "title": "Oxisuran reduction by rabbit tissue preparations.", "content": "Oxisuran, 2-((methylsulfinyl)acetyl)pyridine is reduced to alpha-((methylsulfinyl)methyl-2-pyridinemethanol, oxisuranol, by cytoplasmic enzymes from rabbit liver, kidney, brain, intestine, and lung. The cytoplasmic enzyme from liver is dependent on NADPH as cofactor and has an optimal pH of 6.0. Enzymatic activity is also present in liver mitochondria but at a lower specific activity. The cytoplasmic extracts catalyze the formation of two oxisuranol products, presumably the diastereoisomers described by Di Carlo and associates from in vivo studies. Verification of the product as oxisuranol was accomplished by thin-layer chromatography and mass spectrometry.", "contents": "Oxisuran reduction by rabbit tissue preparations. Oxisuran, 2-((methylsulfinyl)acetyl)pyridine is reduced to alpha-((methylsulfinyl)methyl-2-pyridinemethanol, oxisuranol, by cytoplasmic enzymes from rabbit liver, kidney, brain, intestine, and lung. The cytoplasmic enzyme from liver is dependent on NADPH as cofactor and has an optimal pH of 6.0. Enzymatic activity is also present in liver mitochondria but at a lower specific activity. The cytoplasmic extracts catalyze the formation of two oxisuranol products, presumably the diastereoisomers described by Di Carlo and associates from in vivo studies. Verification of the product as oxisuranol was accomplished by thin-layer chromatography and mass spectrometry."}
{"id": "PMID:6229", "title": "SKF 525-A inhibition, induction, and 452-nm complex formation.", "content": "After administration of SKF 525-A to rats a portion of the cytochrome P-450 in hepatic microsomes was found in the reduced form as a stable complex absorbing at 452 nm. As much as 40% of the total cytochrome P-450 was bound in the complexed form after a single administration of SKF 525-A. The addition of potassium ferricyanide (50 muM) to hepatic microsomes from SKF 525-A-treated rats destroyed the complex and made the total cytochrome P-450 available for carbon monoxide binding. At early times after administration of SKF 525-A, when the amount of complexed cytochrome P-450 was maximum, mixed-function oxidase activities (p-nitroanisole O-demethylase and norbenzphetamine 455-nm complex formation) were greatly inhibited. Later, as the amount of complexed cytochrome P-450 slowly decreased, these mixed-function oxidase activities gradually returned and reached control values in about 48 hr. Induction with daily doses of SKF 525-A for several days increased total cytochrome P-450 content up to 5-fold, which was more than induction with phenobarbital, but this was evident only after destruction of the complex with ferricyanide. The maximum increase in uncomplexed cytochrome P-450 was only 2-fold. Treatment of these microsomal suspensions with ferricyanide enhanced ethylmorphine N-demethylase, p-nitroanisole O-demethylase and norbenzphetamine 455-nm complex formation.", "contents": "SKF 525-A inhibition, induction, and 452-nm complex formation. After administration of SKF 525-A to rats a portion of the cytochrome P-450 in hepatic microsomes was found in the reduced form as a stable complex absorbing at 452 nm. As much as 40% of the total cytochrome P-450 was bound in the complexed form after a single administration of SKF 525-A. The addition of potassium ferricyanide (50 muM) to hepatic microsomes from SKF 525-A-treated rats destroyed the complex and made the total cytochrome P-450 available for carbon monoxide binding. At early times after administration of SKF 525-A, when the amount of complexed cytochrome P-450 was maximum, mixed-function oxidase activities (p-nitroanisole O-demethylase and norbenzphetamine 455-nm complex formation) were greatly inhibited. Later, as the amount of complexed cytochrome P-450 slowly decreased, these mixed-function oxidase activities gradually returned and reached control values in about 48 hr. Induction with daily doses of SKF 525-A for several days increased total cytochrome P-450 content up to 5-fold, which was more than induction with phenobarbital, but this was evident only after destruction of the complex with ferricyanide. The maximum increase in uncomplexed cytochrome P-450 was only 2-fold. Treatment of these microsomal suspensions with ferricyanide enhanced ethylmorphine N-demethylase, p-nitroanisole O-demethylase and norbenzphetamine 455-nm complex formation."}
{"id": "PMID:6230", "title": "In vivo phenolic metabolites of N-alkylamphetamines in the rat. Evidence in favor of catechol formation.", "content": "The major in vivo metabolites of 1-phenyl-2-(n-propylamino)propane (N-n-propylamphetamine) in the rat were phenolic compounds, identified as 1-(4-hydroxyphenyl)-2-(n-propylamino)-propane (metabolite A) and 1-(4-hydroxy-3-methoxyphenyl)-2-(n-propylamino)propane (metabolite B) by gas chromatography-mass spectrometry, and by comparison with authentic synthetic samples of A and B. Metabolites A and B were formed from the substrate in 18.3% and 3.3% yields, respectively, and are excreted in the urine mainly in conjugated form. In vivo metabolism in the rat of the homolog, 1-phenyl-2-(n-butylamino)propane (N-n-butylamphetamine) resulted in the formation of two homologous metabolites in similar yields, which were tentatively identified, from their gas chromatographic and mass spectrometric behav-propane (metabolite A) and 1-(4-hydroxy-3-methoxyphenyl)-2-(n-propylamino)propane (metaboior and by comparison with metabolites A and B, as 2-(n-butylamino)-1-(4-hydroxyphenyl)propane (metabolite C) and 2-(n-butylamino)-1-(4-hydroxy-3-methoxyphenyl)propane (metabolite D). It is suggested that the methylated metabolites B and D were formed from metabolites A and C, respectively, via catecholamine intermediates.", "contents": "In vivo phenolic metabolites of N-alkylamphetamines in the rat. Evidence in favor of catechol formation. The major in vivo metabolites of 1-phenyl-2-(n-propylamino)propane (N-n-propylamphetamine) in the rat were phenolic compounds, identified as 1-(4-hydroxyphenyl)-2-(n-propylamino)-propane (metabolite A) and 1-(4-hydroxy-3-methoxyphenyl)-2-(n-propylamino)propane (metabolite B) by gas chromatography-mass spectrometry, and by comparison with authentic synthetic samples of A and B. Metabolites A and B were formed from the substrate in 18.3% and 3.3% yields, respectively, and are excreted in the urine mainly in conjugated form. In vivo metabolism in the rat of the homolog, 1-phenyl-2-(n-butylamino)propane (N-n-butylamphetamine) resulted in the formation of two homologous metabolites in similar yields, which were tentatively identified, from their gas chromatographic and mass spectrometric behav-propane (metabolite A) and 1-(4-hydroxy-3-methoxyphenyl)-2-(n-propylamino)propane (metaboior and by comparison with metabolites A and B, as 2-(n-butylamino)-1-(4-hydroxyphenyl)propane (metabolite C) and 2-(n-butylamino)-1-(4-hydroxy-3-methoxyphenyl)propane (metabolite D). It is suggested that the methylated metabolites B and D were formed from metabolites A and C, respectively, via catecholamine intermediates."}
{"id": "PMID:6227", "title": "Decrease in the activity of the drug-metabolizing enzymes of rat liver following the administration of tilorone hydrochloride.", "content": "Tilorone hydrochloride, 2,7-bias(2-(diethylamino)ethoxy(fluoren-9-one dihydrochloride, has been studied to determine its effect on the drug-metabolizing enzymes of the liver of male Charles River CD strain rats. Single and multiple doses of tilorone-HCl, 100 mg/kg/day po, were used. Most experiments were performed 24 hr after the last dose, except for a study 5 hr after dosing, and those in which the duration of effects of tilorone hydrochloride were determined. The hexobarbital sleeping time was prolonged after both single doses and four doses of tilorone hydrochloride. The 4-dose regimen prolonged the zoxazolamine paralysis time but the single dose did not. A decrease in microsomal protein was observed after the single- and 4-dose regimens but not after 21 daily doses of tilorone-HCl. Cytochrome P-450 content of microsomes was decreased by the single doses, 100 and 250 mg/kg po, and by 4 and 21 doses of 100 mg/kg/day po. Activities of aminopyrine demethylase and hexobarbital oxidase also were decreased by the above regimens, but the activity of hexobarbital oxidase was affected more markedly. Electron micrographs of rat liver, after treatment with tilorone-HCl, 100 mg/kg/day for 21 days, revealed many membranous structures in the form of whorls.", "contents": "Decrease in the activity of the drug-metabolizing enzymes of rat liver following the administration of tilorone hydrochloride. Tilorone hydrochloride, 2,7-bias(2-(diethylamino)ethoxy(fluoren-9-one dihydrochloride, has been studied to determine its effect on the drug-metabolizing enzymes of the liver of male Charles River CD strain rats. Single and multiple doses of tilorone-HCl, 100 mg/kg/day po, were used. Most experiments were performed 24 hr after the last dose, except for a study 5 hr after dosing, and those in which the duration of effects of tilorone hydrochloride were determined. The hexobarbital sleeping time was prolonged after both single doses and four doses of tilorone hydrochloride. The 4-dose regimen prolonged the zoxazolamine paralysis time but the single dose did not. A decrease in microsomal protein was observed after the single- and 4-dose regimens but not after 21 daily doses of tilorone-HCl. Cytochrome P-450 content of microsomes was decreased by the single doses, 100 and 250 mg/kg po, and by 4 and 21 doses of 100 mg/kg/day po. Activities of aminopyrine demethylase and hexobarbital oxidase also were decreased by the above regimens, but the activity of hexobarbital oxidase was affected more markedly. Electron micrographs of rat liver, after treatment with tilorone-HCl, 100 mg/kg/day for 21 days, revealed many membranous structures in the form of whorls."}
{"id": "PMID:6231", "title": "Biotransformation of mazindol. I. Isolation and identification of some metabolites from rat urine.", "content": "Three metabolites of tritium-labeled mazindol were isolated from rat urine by the inverse isotope-dilution technique in which the labeled metabolites were synthesized by a second, smaller group of rats. These metabolites were isolated by Amberlite XAD-2 chromatography and silica gel column and preparative thin-layer chromatography. The major metabolite (II) was shown by mass spectrometry of its trimethylsilyl derivative. NMR spectroscopy, and degradation studies to be 5-(p-chlorophenyl)-2,5-dihydro-5-hydroxy-3H-imidazol(2,1-a)isoindol-3-one. A comparison of its mass spectrum with that of an authentic sample prepared from 1-(p-chlorophenyl)-3-ethoxy-1-methoxy-1H-isoindole and glycine ethyl ester confirmed the assignment. Metabolite III was shown by its mass spectrum, NMR spectrum, degradation, and analogy with metabolite II to be 5-(p-chlorophenyl)-2,5-dihydro-2,5-dihydroxy-3H-imidazo (2,1-a)isoindol-3-one. Only a small amount of metabolite IV was isolated as an artifact, 3-(p-chlorophenyl)-2-glycyl-3-methoxy-1-isoindolinone, as shown by its mass spectrum and degradation to 2-(p-chlorobenzoy)benzoic acid. The metabolite IV is believed to be the corresponding 3-hydroxy compound. Synthesis of IV by base-catalyzed hydrolysis of metabolite II supports the structural assignment. In addition, the facile conversion of synthetic IV into the corresponding 3-methoxy derivative by acidic methanol was also observed.", "contents": "Biotransformation of mazindol. I. Isolation and identification of some metabolites from rat urine. Three metabolites of tritium-labeled mazindol were isolated from rat urine by the inverse isotope-dilution technique in which the labeled metabolites were synthesized by a second, smaller group of rats. These metabolites were isolated by Amberlite XAD-2 chromatography and silica gel column and preparative thin-layer chromatography. The major metabolite (II) was shown by mass spectrometry of its trimethylsilyl derivative. NMR spectroscopy, and degradation studies to be 5-(p-chlorophenyl)-2,5-dihydro-5-hydroxy-3H-imidazol(2,1-a)isoindol-3-one. A comparison of its mass spectrum with that of an authentic sample prepared from 1-(p-chlorophenyl)-3-ethoxy-1-methoxy-1H-isoindole and glycine ethyl ester confirmed the assignment. Metabolite III was shown by its mass spectrum, NMR spectrum, degradation, and analogy with metabolite II to be 5-(p-chlorophenyl)-2,5-dihydro-2,5-dihydroxy-3H-imidazo (2,1-a)isoindol-3-one. Only a small amount of metabolite IV was isolated as an artifact, 3-(p-chlorophenyl)-2-glycyl-3-methoxy-1-isoindolinone, as shown by its mass spectrum and degradation to 2-(p-chlorobenzoy)benzoic acid. The metabolite IV is believed to be the corresponding 3-hydroxy compound. Synthesis of IV by base-catalyzed hydrolysis of metabolite II supports the structural assignment. In addition, the facile conversion of synthetic IV into the corresponding 3-methoxy derivative by acidic methanol was also observed."}
{"id": "PMID:6232", "title": "Disposition of bethanidine, N-benzyl-N',N''-dimethylguanidine, in the rat, dog and man.", "content": "Bethanidine is metabolized in the rat and dog to a significant degree to N-benzyl-N'-methylguanidine, N-benzylguanidine, N-hydroxybenzyl-N'-methylguanidine, N-methylguanidine, N-hydroxybenzyl-N',N''-di-methylguanidine, and benzoic acid, whereas in man the drug is not metabolized. It is readily absorbed in all three species. The elimination kinetics in man show a difference between the urinary excretion rate and the rate of decline in the blood. Whole body autoradiograms showed a high concentration of drug in rat tissues rich in adrenergic nerve terminals, but insignificant penetration, if any, of the blood-brain barrier.", "contents": "Disposition of bethanidine, N-benzyl-N',N''-dimethylguanidine, in the rat, dog and man. Bethanidine is metabolized in the rat and dog to a significant degree to N-benzyl-N'-methylguanidine, N-benzylguanidine, N-hydroxybenzyl-N'-methylguanidine, N-methylguanidine, N-hydroxybenzyl-N',N''-di-methylguanidine, and benzoic acid, whereas in man the drug is not metabolized. It is readily absorbed in all three species. The elimination kinetics in man show a difference between the urinary excretion rate and the rate of decline in the blood. Whole body autoradiograms showed a high concentration of drug in rat tissues rich in adrenergic nerve terminals, but insignificant penetration, if any, of the blood-brain barrier."}
{"id": "PMID:6233", "title": "Disposition of (15,16-3H)naltrexone in the central nervous system of the rat.", "content": "After injection of (15,16-3H)naltrexone (10 mg/kg s.c.) in male Wistar rats, peak concentrations of drug occurred in brain and plasma within 0.5 hr. Levels of naltrexone were sustained in brain between 2 and 24 hr and were barely detectable at 48 hr. Significant amounts of metabolities were present in brain and plasma at longer time periods. The t1/2 of naltrexone in brain and plasma were approximately 8.0 and 11.4 hr. respectively. The brain/plasma ratios of naltrexone at earlier times (0.5-1 hr) were higher than those at later times. The binding of naltrexone in vitro with rat plasma proteins in concentrations of 1-10 mug/ml ranged between 41 and 59% 6beta-Naltrexol was present in very small amounts in brain but not in plasma. In addition to 7,8-dihydro-14-hydroxynormophinone and 7,8-dihydro-14-hydroxynormophine, tentative evidence was obtained for three other metabolites of naltrexone in brain. These metabolites were also present in plasma in addition to free and conjugated naltrexone and its N-dealkylated metabolites.", "contents": "Disposition of (15,16-3H)naltrexone in the central nervous system of the rat. After injection of (15,16-3H)naltrexone (10 mg/kg s.c.) in male Wistar rats, peak concentrations of drug occurred in brain and plasma within 0.5 hr. Levels of naltrexone were sustained in brain between 2 and 24 hr and were barely detectable at 48 hr. Significant amounts of metabolities were present in brain and plasma at longer time periods. The t1/2 of naltrexone in brain and plasma were approximately 8.0 and 11.4 hr. respectively. The brain/plasma ratios of naltrexone at earlier times (0.5-1 hr) were higher than those at later times. The binding of naltrexone in vitro with rat plasma proteins in concentrations of 1-10 mug/ml ranged between 41 and 59% 6beta-Naltrexol was present in very small amounts in brain but not in plasma. In addition to 7,8-dihydro-14-hydroxynormophinone and 7,8-dihydro-14-hydroxynormophine, tentative evidence was obtained for three other metabolites of naltrexone in brain. These metabolites were also present in plasma in addition to free and conjugated naltrexone and its N-dealkylated metabolites."}
{"id": "PMID:6234", "title": "Mirex kinetics in the rhesus monkey. I. Disposition and excretion.", "content": "Three female rhesus monkeys were given 14C-Mirex (5.23 mCi/mmol) iv (two animals) or po (one animal) in a dose of about 1 mg/kg for the purpose of determining the distribution and excretion of this polycyclic perchlorinated insecticide. Blood, plasma, urine, feces, and tissue samples were analyzed for 14C content. Monkeys were autopsied 23, 106, and 388 days after receiving 14C-Mirex. Following iv administration, plasma 14C showed a rapid decrease over the first few hours from the initial high levels. In the monkey given the compound orally, 14C first appeared in the plasma at 2 hr and reached a maximum at 5 hr. Thereafter, the decline in plasma radioactivity paralleled that found in the animals dosed i.v. After 2 weeks, the rate of decline in all animals was very slow. Excretion and tissue distribution of Mirex were essentially the same whether the compound was given po or iv. Less than 0.6% of the dose was found in the urine. 14C was excreted in the feces for the duration of the experiment with a maximum cumulative excretion of 7% after 388 days. At autopsy all tissues analyzed contained 14C. The highest concentration of 14C was found in the fat (estimated to contain at least 80% of the dose), followed by adrenal, peripheral nerve, thyroid, and skin. Chemical analysis of the nature of the radioactivity in fat and feces showed that at least 95% and was present as unchanged Mirex. There was a small amount of a compound more polar than Mirex in the feces, containing less than 3% of the fecal radioactivity.", "contents": "Mirex kinetics in the rhesus monkey. I. Disposition and excretion. Three female rhesus monkeys were given 14C-Mirex (5.23 mCi/mmol) iv (two animals) or po (one animal) in a dose of about 1 mg/kg for the purpose of determining the distribution and excretion of this polycyclic perchlorinated insecticide. Blood, plasma, urine, feces, and tissue samples were analyzed for 14C content. Monkeys were autopsied 23, 106, and 388 days after receiving 14C-Mirex. Following iv administration, plasma 14C showed a rapid decrease over the first few hours from the initial high levels. In the monkey given the compound orally, 14C first appeared in the plasma at 2 hr and reached a maximum at 5 hr. Thereafter, the decline in plasma radioactivity paralleled that found in the animals dosed i.v. After 2 weeks, the rate of decline in all animals was very slow. Excretion and tissue distribution of Mirex were essentially the same whether the compound was given po or iv. Less than 0.6% of the dose was found in the urine. 14C was excreted in the feces for the duration of the experiment with a maximum cumulative excretion of 7% after 388 days. At autopsy all tissues analyzed contained 14C. The highest concentration of 14C was found in the fat (estimated to contain at least 80% of the dose), followed by adrenal, peripheral nerve, thyroid, and skin. Chemical analysis of the nature of the radioactivity in fat and feces showed that at least 95% and was present as unchanged Mirex. There was a small amount of a compound more polar than Mirex in the feces, containing less than 3% of the fecal radioactivity."}
{"id": "PMID:6235", "title": "Mirex kinetics in the rhesus monkey. II. Pharmacokinetic model.", "content": "14C-Mirex was given iv and po to female rhesus monkeys (Macaca mulatta) and radioactivity was measured in plasma, urine, and feces at intervals after dosing and in tissues when animals were killed. Graphical analysis of plots of the logarithm of plasma concentration vs. time was used to provide estimates of the values of the first-order rate constants required by the proposed pharmacokinetic models. A BASIC-language program, FITKIN, was used to obtain numerical solutions to the differential equations for each model and to adjust the estimates to obtain a normalized, least squares fit. Of several models postulated, a mammillary, four-compartment, open-system model, providing for the urinary excretion of Mirex from a \"central\" compartment and for the fecal excretion of Mirex from a \"fast\" tissue compartment, yielded theoretical data in agreement with observed values. This model predicted that the accumulation of Mirex into fat would be retarded by the presence of a \"slow\" tissue compartment so that distribution equilibrium would take about half a year. From that time to the end of a 5-year projection, little decline in the quantities of Mirex was predicted for any compartment. Sequestration in fat and a lack of metabolism were responsible for the long biological half-life of Mirex in the rhesus monkey.", "contents": "Mirex kinetics in the rhesus monkey. II. Pharmacokinetic model. 14C-Mirex was given iv and po to female rhesus monkeys (Macaca mulatta) and radioactivity was measured in plasma, urine, and feces at intervals after dosing and in tissues when animals were killed. Graphical analysis of plots of the logarithm of plasma concentration vs. time was used to provide estimates of the values of the first-order rate constants required by the proposed pharmacokinetic models. A BASIC-language program, FITKIN, was used to obtain numerical solutions to the differential equations for each model and to adjust the estimates to obtain a normalized, least squares fit. Of several models postulated, a mammillary, four-compartment, open-system model, providing for the urinary excretion of Mirex from a \"central\" compartment and for the fecal excretion of Mirex from a \"fast\" tissue compartment, yielded theoretical data in agreement with observed values. This model predicted that the accumulation of Mirex into fat would be retarded by the presence of a \"slow\" tissue compartment so that distribution equilibrium would take about half a year. From that time to the end of a 5-year projection, little decline in the quantities of Mirex was predicted for any compartment. Sequestration in fat and a lack of metabolism were responsible for the long biological half-life of Mirex in the rhesus monkey."}
{"id": "PMID:6240", "title": "Medication for hyperkinetic children.", "content": "The hyperkinetic syndrome is a symptom complex of hyperactivity, short attention span, distractibility, impulsivity, learning difficulties, other behaviour problems and 'equivocal' neurological signs. However, none of these terms has ever been objectively defined and at present diagnosis is largely a matter of clinical judgement. In the management of the disorder, drugs do have a place but the decision to use medication is a complex procedure diagnostically and therapeutically calling for the highest in clinical skill and medical supervision. The most useful medication at present is the stimulant group of drugs, particularly dextroamphetamine and methylphenidate. Antipsychotic drugs are sometimes useful but carry the risk of depressing higher CNS functions such as attention and cognition. Other drugs which have been shown to be of value include tricyclic antidepressants (although their effect is less predictable and less striking than that of the stimulants) and pemoline.", "contents": "Medication for hyperkinetic children. The hyperkinetic syndrome is a symptom complex of hyperactivity, short attention span, distractibility, impulsivity, learning difficulties, other behaviour problems and 'equivocal' neurological signs. However, none of these terms has ever been objectively defined and at present diagnosis is largely a matter of clinical judgement. In the management of the disorder, drugs do have a place but the decision to use medication is a complex procedure diagnostically and therapeutically calling for the highest in clinical skill and medical supervision. The most useful medication at present is the stimulant group of drugs, particularly dextroamphetamine and methylphenidate. Antipsychotic drugs are sometimes useful but carry the risk of depressing higher CNS functions such as attention and cognition. Other drugs which have been shown to be of value include tricyclic antidepressants (although their effect is less predictable and less striking than that of the stimulants) and pemoline."}
{"id": "PMID:6242", "title": "Some aspects of the pharmacology of beta-adrenorecptor blockers.", "content": "The pharmacodynamic properties of a beta-blocker are mainly determined by its affinity to beta1 and beta2-receptors respectively and by its intrinsic activity. It is suggested that there is no absolute organ separation of the two receptor sub-types. Instead both beta1 and beta2-receptors are involved in the mediation of the same effect. The frequency distribution ratio of beta1/beta2-receptors varied markedly among various effector responses. A non-selective and a beta1-selective blocker may have different haemodynamic effects when the levels of circulating adrenaline are high, because of their markedly different potency in inhibiting the beta2-mediated vasodilator effect of adrenaline. Data are presented which suggest the existence of a presynaptic beta1-receptor mediating a positive feedback mechanism on neuronal release of noradrenaline.", "contents": "Some aspects of the pharmacology of beta-adrenorecptor blockers. The pharmacodynamic properties of a beta-blocker are mainly determined by its affinity to beta1 and beta2-receptors respectively and by its intrinsic activity. It is suggested that there is no absolute organ separation of the two receptor sub-types. Instead both beta1 and beta2-receptors are involved in the mediation of the same effect. The frequency distribution ratio of beta1/beta2-receptors varied markedly among various effector responses. A non-selective and a beta1-selective blocker may have different haemodynamic effects when the levels of circulating adrenaline are high, because of their markedly different potency in inhibiting the beta2-mediated vasodilator effect of adrenaline. Data are presented which suggest the existence of a presynaptic beta1-receptor mediating a positive feedback mechanism on neuronal release of noradrenaline."}
{"id": "PMID:6236", "title": "Correlation of mouse tissue distribution of arabinosylcytosine in vivo with enzymatic activities in vitro.", "content": "The distribution of arabinosylcytosine (ara-C) and its metabolites has been measured in the liver, small intestine, spleen, and kidney of mice inoculated ip 5-6 days earlier with L1210 leukemia cells. Two major metabolites were found in the tissues--the nucleotides and the deaminated inactive product, arabinosyluracil (ara-U). The decay curve of ara-C in most of these tissues was curvilinear; the ara-C half-lives estimated from the terminal phases were 8. 11, 12, and 12 hr for spleen, kidney, intestine, and liver tissues, respectively. The ara-C half-life was not correlated with the deoxycytidine deaminase activity in the tissues. However, the deaminase activity in vitro correlated well with the amount of ara-U present in vivo. Similar analyses were made for L1210 leukemic cells and ascites fluid. A high nucleotide level was found in the cells and a significant amount of nucleotides was also identifiable in the ascites fluid. The activities of deoxycytidine kinase, but not of deoxycytidine deaminase, in host tissues of mice inoculated with L1210 leukemic cells sensitive to ara-C were greater than in those of normal mice. The phosphorylating activities in vitro correlated with the amount of nucleotide present in vivo in mice bearing  L1210 leukemic cells. However, the infiltration of leukemic cells containing high kinase activities into the host tissues accounted for most, if not all, of the nucleotide level in these tissues. This is further evidenced by the fact that inoculating mice with L1210 leukemic cells resistant to ara-C did not alter the kinase activity or nucleotide levels of the host tissues; these resistant cells contain negligible amounts of ara-C phosphorylating activities.", "contents": "Correlation of mouse tissue distribution of arabinosylcytosine in vivo with enzymatic activities in vitro. The distribution of arabinosylcytosine (ara-C) and its metabolites has been measured in the liver, small intestine, spleen, and kidney of mice inoculated ip 5-6 days earlier with L1210 leukemia cells. Two major metabolites were found in the tissues--the nucleotides and the deaminated inactive product, arabinosyluracil (ara-U). The decay curve of ara-C in most of these tissues was curvilinear; the ara-C half-lives estimated from the terminal phases were 8. 11, 12, and 12 hr for spleen, kidney, intestine, and liver tissues, respectively. The ara-C half-life was not correlated with the deoxycytidine deaminase activity in the tissues. However, the deaminase activity in vitro correlated well with the amount of ara-U present in vivo. Similar analyses were made for L1210 leukemic cells and ascites fluid. A high nucleotide level was found in the cells and a significant amount of nucleotides was also identifiable in the ascites fluid. The activities of deoxycytidine kinase, but not of deoxycytidine deaminase, in host tissues of mice inoculated with L1210 leukemic cells sensitive to ara-C were greater than in those of normal mice. The phosphorylating activities in vitro correlated with the amount of nucleotide present in vivo in mice bearing  L1210 leukemic cells. However, the infiltration of leukemic cells containing high kinase activities into the host tissues accounted for most, if not all, of the nucleotide level in these tissues. This is further evidenced by the fact that inoculating mice with L1210 leukemic cells resistant to ara-C did not alter the kinase activity or nucleotide levels of the host tissues; these resistant cells contain negligible amounts of ara-C phosphorylating activities."}
{"id": "PMID:6243", "title": "Clinical pharmacokinetics of beta-adrenoreceptors blockers.", "content": "beta-blockers are completely and rapidly absorbed from the gastro-intestinal tract. In their first passage through the liver they are metabolised to a varying extent - the so-called first-pass effect. For propranolol and alprenolol this degradation is partly compensated for by the formation of active metabolites, the 4-OH derivatives. The beta-blocking effect is linearly correlated with the log plasma concentration of the drugs. Although there is also a relationship between the antihypertensive effect of the drugs and their log plasma concentration, it seems to be of limited value to determine the plasma levels of the drugs in order to adjust the therapeutic dose. This is due to the great inter-individual differences of the plasma concentration-antihypertensive effect relationship. It is essential to investigate  whether pharmacologically active metabolites are formed. These may not only influence the relationship between plasma concentration and therapeutic effect but may also modify the pharmacological profile of the drug. The plasma levels, and thereby the effects of the drugs, can be modified by other drugs and diseases. Thus practolol, which is mainly eliminated via the kidneys, has a longer plasma half-life in patients with renal failure. The plasma of propranolol, which is eliminated from the body by bio-transformation in the liver, is not prolonged in patients with renal failure, but its metabolites are excreted at a lower rate in such patients. Although most beta-blockers have a relatively short plasma half-life (2 to 5 hours), the drugs can be administered twice daily in clinical practice. This due to the fact that the effect declines according to zero-order kinetics while the elimination of the drug follows first-order kinetics. It is desirable that all these factors are clarified before a drug is used in clinical practice as they all will have an influence on its dose regimen. The responsibility for this must be on the drug company, which must be able to inform physicians not only about the standard dosage of the drug but also how other drugs and diseases can change the individual responses to the drug.", "contents": "Clinical pharmacokinetics of beta-adrenoreceptors blockers. beta-blockers are completely and rapidly absorbed from the gastro-intestinal tract. In their first passage through the liver they are metabolised to a varying extent - the so-called first-pass effect. For propranolol and alprenolol this degradation is partly compensated for by the formation of active metabolites, the 4-OH derivatives. The beta-blocking effect is linearly correlated with the log plasma concentration of the drugs. Although there is also a relationship between the antihypertensive effect of the drugs and their log plasma concentration, it seems to be of limited value to determine the plasma levels of the drugs in order to adjust the therapeutic dose. This is due to the great inter-individual differences of the plasma concentration-antihypertensive effect relationship. It is essential to investigate  whether pharmacologically active metabolites are formed. These may not only influence the relationship between plasma concentration and therapeutic effect but may also modify the pharmacological profile of the drug. The plasma levels, and thereby the effects of the drugs, can be modified by other drugs and diseases. Thus practolol, which is mainly eliminated via the kidneys, has a longer plasma half-life in patients with renal failure. The plasma of propranolol, which is eliminated from the body by bio-transformation in the liver, is not prolonged in patients with renal failure, but its metabolites are excreted at a lower rate in such patients. Although most beta-blockers have a relatively short plasma half-life (2 to 5 hours), the drugs can be administered twice daily in clinical practice. This due to the fact that the effect declines according to zero-order kinetics while the elimination of the drug follows first-order kinetics. It is desirable that all these factors are clarified before a drug is used in clinical practice as they all will have an influence on its dose regimen. The responsibility for this must be on the drug company, which must be able to inform physicians not only about the standard dosage of the drug but also how other drugs and diseases can change the individual responses to the drug."}
{"id": "PMID:6244", "title": "Metabolic effects of beta-adrenoreceptor blockers.", "content": "The effects of beta-blockade on glucose metabolism are complex. Some patients with impaired glucose tolerance while taking a non-selective beta-blocker, showed some improvement in glucose tolerance when therapy was changed to a beta1-blocker (metoprolol). Serum K+ values tend to rise slightly on beta-blocking therapy; small increases in serum urea and creatinine also occur. A rise in plasma triglycerides was noted in patients starting beta-blocking therapy; this effect seemed to be more marked on metoprolol than on non-selective beta-blockers.", "contents": "Metabolic effects of beta-adrenoreceptor blockers. The effects of beta-blockade on glucose metabolism are complex. Some patients with impaired glucose tolerance while taking a non-selective beta-blocker, showed some improvement in glucose tolerance when therapy was changed to a beta1-blocker (metoprolol). Serum K+ values tend to rise slightly on beta-blocking therapy; small increases in serum urea and creatinine also occur. A rise in plasma triglycerides was noted in patients starting beta-blocking therapy; this effect seemed to be more marked on metoprolol than on non-selective beta-blockers."}
{"id": "PMID:6245", "title": "Haemodynamic effects of beta-adrenorecptor blockers in hypertension.", "content": "The haemodynamic effect pattern of beta-blockers in hypertension is discussed. The time curve of the antihypertensive effect differs from that of cardiac beta-blockade. The antihypertensive effect is characterized by a slower onset at the start of treatment and a more gradual disappearance when therapy is withdrawn. It appears that the crucial effect of beta-blockers in hypertension is a gradually developing reduction in total peripheral vascular resistance. The mechanism of this apparent vasodilator action is unknown. Various possible factors involved are mentioned. One is a reduced efficiency of transmitter release from the peripheral adrenergic neuron. Such an action may contribute to the antihypertensive effect, as judged by results of animal experiments described.", "contents": "Haemodynamic effects of beta-adrenorecptor blockers in hypertension. The haemodynamic effect pattern of beta-blockers in hypertension is discussed. The time curve of the antihypertensive effect differs from that of cardiac beta-blockade. The antihypertensive effect is characterized by a slower onset at the start of treatment and a more gradual disappearance when therapy is withdrawn. It appears that the crucial effect of beta-blockers in hypertension is a gradually developing reduction in total peripheral vascular resistance. The mechanism of this apparent vasodilator action is unknown. Various possible factors involved are mentioned. One is a reduced efficiency of transmitter release from the peripheral adrenergic neuron. Such an action may contribute to the antihypertensive effect, as judged by results of animal experiments described."}
{"id": "PMID:6246", "title": "Effects of beta-adrenoreceptor blocking drugs on adrenergic transmission.", "content": "The peripheral actions of beta-adrenoreceptor antagonists on adrenergic transmitter mechanisms have been reviewed. In addition to receptor blockade, beta-adrenoreceptor antagonists may in high concentrations inhibit neuronal uptake of noradrenaline; inhibit monoamine oxidase; inhibit the uptake of noradrenaline into transmitter storage vesicles and inhibit the extraneuronal uptake of noradrenaline. High concentrations of beta-adrenoreceptor antagonists (threshold about 30 muM) also release noradrenaline from intraneuronal stores; however, their intrinsic sympathomimetic activity is generally attributed to their partial agonist property. Beta-adrenoreceptor antagonists possess adrenergic neurone blocking activity and quinidine-like or local anaesthetic activity. The existance of a positive feedback mechanism involving prejunctional beta-adrenoreceptors is discussed. It is suggested that bradycardia produced by beta-adrenoreceptor antagonists is due to blockade of the action of circulating catecholamines or of transmitter noradrenaline at cardiac extrajunctional beta-adrenoreceptor sites.", "contents": "Effects of beta-adrenoreceptor blocking drugs on adrenergic transmission. The peripheral actions of beta-adrenoreceptor antagonists on adrenergic transmitter mechanisms have been reviewed. In addition to receptor blockade, beta-adrenoreceptor antagonists may in high concentrations inhibit neuronal uptake of noradrenaline; inhibit monoamine oxidase; inhibit the uptake of noradrenaline into transmitter storage vesicles and inhibit the extraneuronal uptake of noradrenaline. High concentrations of beta-adrenoreceptor antagonists (threshold about 30 muM) also release noradrenaline from intraneuronal stores; however, their intrinsic sympathomimetic activity is generally attributed to their partial agonist property. Beta-adrenoreceptor antagonists possess adrenergic neurone blocking activity and quinidine-like or local anaesthetic activity. The existance of a positive feedback mechanism involving prejunctional beta-adrenoreceptors is discussed. It is suggested that bradycardia produced by beta-adrenoreceptor antagonists is due to blockade of the action of circulating catecholamines or of transmitter noradrenaline at cardiac extrajunctional beta-adrenoreceptor sites."}
{"id": "PMID:6247", "title": "The role of renin in the antihypertensive action of beta-adrenoreceptor blocking agents.", "content": "Since the original reports suggesting that the antihypertensive action of beta-adrenoreceptor blocking drugs is related to their inhibitory action on renin release, much evidence has been put forward both to refute and support this hypothesis. Our studies of the acute and chronic effects of treatment with propranolol in hypertensive patients showed that the antihypertensive action of the drug was of later onset than the initial cardio-depressant and renin-suppressive effects and had little relationship to the pre-treatment levels of treatment-induced changes in plasma renin activity (PRA). When pindolol was substituted for propranolol in these studies PRA rose, but blood pressure control was undisturbed. Again, in animal experiments, although a range of different beta-adrenoreceptor blocking agents induced decreases in both blood pressure and PRA, the hypotensive effects of pindolol was associated with a rise in PRA. Further, PRA proved to be a poor guide to therapeutic effectiveness in the treatment of an unselected population of hypertensive patients with propranolol. It is concluded that the antihypertensive action of beta-adrenoreceptor blocking agents, as a class, is not dependent upon suppression of PRA.", "contents": "The role of renin in the antihypertensive action of beta-adrenoreceptor blocking agents. Since the original reports suggesting that the antihypertensive action of beta-adrenoreceptor blocking drugs is related to their inhibitory action on renin release, much evidence has been put forward both to refute and support this hypothesis. Our studies of the acute and chronic effects of treatment with propranolol in hypertensive patients showed that the antihypertensive action of the drug was of later onset than the initial cardio-depressant and renin-suppressive effects and had little relationship to the pre-treatment levels of treatment-induced changes in plasma renin activity (PRA). When pindolol was substituted for propranolol in these studies PRA rose, but blood pressure control was undisturbed. Again, in animal experiments, although a range of different beta-adrenoreceptor blocking agents induced decreases in both blood pressure and PRA, the hypotensive effects of pindolol was associated with a rise in PRA. Further, PRA proved to be a poor guide to therapeutic effectiveness in the treatment of an unselected population of hypertensive patients with propranolol. It is concluded that the antihypertensive action of beta-adrenoreceptor blocking agents, as a class, is not dependent upon suppression of PRA."}
{"id": "PMID:6248", "title": "Effects of beta-adrenoreceptor blocking drugs on plasma volume. Renin and aldosterone as components of their antihypertensive action.", "content": "In young males with essential hypertension, propranolol and pindolol in small doses caused significant expansion of plasma volume (PV) after one month which did not prevent a reduction in BP. With higher doses, changes in PV were inconsistent and reductions in plasma renin activity (PRA) and 24-hour aldosterone excretion (AE) not closely related to BP changes. The effects of beta-adrenoreceptor blocking drugs on PV, PRA, and AE do not appear to be important components of their anti-hypertensive action.", "contents": "Effects of beta-adrenoreceptor blocking drugs on plasma volume. Renin and aldosterone as components of their antihypertensive action. In young males with essential hypertension, propranolol and pindolol in small doses caused significant expansion of plasma volume (PV) after one month which did not prevent a reduction in BP. With higher doses, changes in PV were inconsistent and reductions in plasma renin activity (PRA) and 24-hour aldosterone excretion (AE) not closely related to BP changes. The effects of beta-adrenoreceptor blocking drugs on PV, PRA, and AE do not appear to be important components of their anti-hypertensive action."}
{"id": "PMID:6249", "title": "Experience with beta-adrenoreceptor blockers in hypertension.", "content": "At the Dunedin Hypertension Clinic beta-blockers are the drugs of choice for most hypertensive patients, usually in combination with diuretics (especially in older subjects) and often with other drugs in the more severe cases. All beta-blockers have an antihypertensive effect, regardless of other characteristics (e.g. cardio-selectivity, instrinsic sympathomimetic effect, or membrane activity). d-Propranolol has no significant effect on blood pressure. Beta-blockers do not prevent stress-induced (mental arithmetic) rises in blood pressure in hypertensive subjects through the level of blood pressure reached during stress tends to be lower because the base line is lower. Twice-daily dosage of beta-blockers is usually satisfactory.", "contents": "Experience with beta-adrenoreceptor blockers in hypertension. At the Dunedin Hypertension Clinic beta-blockers are the drugs of choice for most hypertensive patients, usually in combination with diuretics (especially in older subjects) and often with other drugs in the more severe cases. All beta-blockers have an antihypertensive effect, regardless of other characteristics (e.g. cardio-selectivity, instrinsic sympathomimetic effect, or membrane activity). d-Propranolol has no significant effect on blood pressure. Beta-blockers do not prevent stress-induced (mental arithmetic) rises in blood pressure in hypertensive subjects through the level of blood pressure reached during stress tends to be lower because the base line is lower. Twice-daily dosage of beta-blockers is usually satisfactory."}
{"id": "PMID:6250", "title": "Use of beta-adrenoreceptor blockers in combination with beta-stimulators in patients with obstructive lung disease.", "content": "Lung function can be reduced not only by a non-selective beta-blocker but also by a selective beta1-receptor blocker. If both types of drug are without intrinsic sympathomimetic activity, the effect of the non-selective drug is more pronounced than that of a beta1-receptor selective drug under basal conditions. The effect of a beta2-receptor stimulating drug on the bronchi is inhibited by a non-selective drug, but much less by a selective beta1-receptor blocker. A selective beta1-receptor blocker can be used in asthmatics when it is combined with optimal anti-asthmatic therapy, while a non-selective drug is contra-indicated in patients with broncho-obstructive diseases. It is necessary to induce bronchodilatation (e.g. with a beta2-stimulator) in order to test whether or not a beta-blocker can be used in broncho-obstructive disease.", "contents": "Use of beta-adrenoreceptor blockers in combination with beta-stimulators in patients with obstructive lung disease. Lung function can be reduced not only by a non-selective beta-blocker but also by a selective beta1-receptor blocker. If both types of drug are without intrinsic sympathomimetic activity, the effect of the non-selective drug is more pronounced than that of a beta1-receptor selective drug under basal conditions. The effect of a beta2-receptor stimulating drug on the bronchi is inhibited by a non-selective drug, but much less by a selective beta1-receptor blocker. A selective beta1-receptor blocker can be used in asthmatics when it is combined with optimal anti-asthmatic therapy, while a non-selective drug is contra-indicated in patients with broncho-obstructive diseases. It is necessary to induce bronchodilatation (e.g. with a beta2-stimulator) in order to test whether or not a beta-blocker can be used in broncho-obstructive disease."}
{"id": "PMID:6251", "title": "Effect of beta-adrenoreceptor blockers on heart rate and blood pressure in dynamic and isometric exercise.", "content": "Previous studies on the effects on heart rate and blood pressure in normals and hypertensive patients during dynamic exercise (ergometer bicycling or treadmill walking) and isometric exercise (sustained handgrip) are reviewed. In one study utilising sub-maximal bicycle exercise in hypertensives, there was a 43% increase in heart rate for a 33% increase in systolic pressure and 5% fall in diastolic pressure. Beta-adrenoreceptor blockade decreased the heart rate level by 18 to 19% for a decrease of systolic blood pressure level by 4 to 11%, whereas the diastolic pressure level was unaffected. A protocol is described utilising a blind indirect blood pressure recording machine (\"Auto-Manometer\") with which cuff inflation and deflation are automatic and constant, and blood pressure values stored at suitable Korotkov sound phases. The machine also records heart rate. By this method, isometric exercise at 50% of maximal voluntary contraction (sustained handgrip) has been studied in normals and hypertensives off and on different treatments. Both in normals and established hypertensives, there was about a 25% increase in systolic blood pressure during isometric exercise for about a 22% increase in diastolic blood pressure, and 26% increase in heart rate. Normotensive women had the lowest rise in blood pressure and the highest rise in heart rate. Beta-Adrenoreceptor blocking agents lowered heart rate during isometric exercise by 15 to 20% but did not affect the blood pressure level. Since resting blood pressure levels were decreased, the percentage rise in pressure was enhanced following beta-blockers. A combination of a beta-blocker, clonidine and/or a vasodilator produced a reduction in both systolic (24%) and diastolic (12%) pressure, as well as in heart rate (18%), during isometric exercise.", "contents": "Effect of beta-adrenoreceptor blockers on heart rate and blood pressure in dynamic and isometric exercise. Previous studies on the effects on heart rate and blood pressure in normals and hypertensive patients during dynamic exercise (ergometer bicycling or treadmill walking) and isometric exercise (sustained handgrip) are reviewed. In one study utilising sub-maximal bicycle exercise in hypertensives, there was a 43% increase in heart rate for a 33% increase in systolic pressure and 5% fall in diastolic pressure. Beta-adrenoreceptor blockade decreased the heart rate level by 18 to 19% for a decrease of systolic blood pressure level by 4 to 11%, whereas the diastolic pressure level was unaffected. A protocol is described utilising a blind indirect blood pressure recording machine (\"Auto-Manometer\") with which cuff inflation and deflation are automatic and constant, and blood pressure values stored at suitable Korotkov sound phases. The machine also records heart rate. By this method, isometric exercise at 50% of maximal voluntary contraction (sustained handgrip) has been studied in normals and hypertensives off and on different treatments. Both in normals and established hypertensives, there was about a 25% increase in systolic blood pressure during isometric exercise for about a 22% increase in diastolic blood pressure, and 26% increase in heart rate. Normotensive women had the lowest rise in blood pressure and the highest rise in heart rate. Beta-Adrenoreceptor blocking agents lowered heart rate during isometric exercise by 15 to 20% but did not affect the blood pressure level. Since resting blood pressure levels were decreased, the percentage rise in pressure was enhanced following beta-blockers. A combination of a beta-blocker, clonidine and/or a vasodilator produced a reduction in both systolic (24%) and diastolic (12%) pressure, as well as in heart rate (18%), during isometric exercise."}
{"id": "PMID:6253", "title": "The kidney and antihypertensive therapy.", "content": "Renal disease and hypertension is a continuing challenge to the nephrologist. At present there are few effective methods of dealing with the common renal diseases such as glomerulonephritis, but fortunately there is now a wide selection of potent antihypertensive agents. Drug resistant hypertension should be a rarity in clinical practice. Malignant hypertension remains a therapeutic emergency. If a patient with hypertension has renal functional impairment it is essential to lower the blood pressure to normal. In the presence of renal failure this should be done with caution so as to avoid a further deterioration in the glomerular filtration rate. However, if the blood pressure is controlled and especially if the renal failure is a result of hypertension alone, renal function may stabilise or even improve, often dramatically.", "contents": "The kidney and antihypertensive therapy. Renal disease and hypertension is a continuing challenge to the nephrologist. At present there are few effective methods of dealing with the common renal diseases such as glomerulonephritis, but fortunately there is now a wide selection of potent antihypertensive agents. Drug resistant hypertension should be a rarity in clinical practice. Malignant hypertension remains a therapeutic emergency. If a patient with hypertension has renal functional impairment it is essential to lower the blood pressure to normal. In the presence of renal failure this should be done with caution so as to avoid a further deterioration in the glomerular filtration rate. However, if the blood pressure is controlled and especially if the renal failure is a result of hypertension alone, renal function may stabilise or even improve, often dramatically."}
{"id": "PMID:6254", "title": "The treatment of resistant hypertension.", "content": "Resistant hypertension can be defined in terms of lack of blood pressure response to hypotensive agents, but there may be a big difference between standing and lying blood pressure levels. In general target organ damage and papilloedema improve if the standing blood pressure is controlled; however, progression can occasionally be documented when only the supine blood pressure remains uncontrolled. Resistant hypertension was a frequent phenomenon when ganglion blocking agents and hydrallazine were the only effective hypotensive agents. With the advent of the thiazides, effective control of the blood pressure became the exception rather than the rule; however, it was not until the advent of adrenergic blocking agents that reduction of supine blood pressures was regularly achieved. The addition of hydrallazine or prazosin to a combination of a thiazide and beta-adrenoreceptor blocking agent produces a further significant fall in the blood pressure lying and standing. This combination will control the blood pressure in most patients, but a few remain refractory to maximum doses and will require treatment with oral diazoxide or minoxidil. Both these powerful vasodilators are very effective in resistant hypertension. Oral diazoxide permits excellent control and allows a 10-fold reduction in the doses of other agents. Minoxidil usually needs to be combined with moderate doses of beta-blocking agents to reduce the marked reflex tachycardia. Only a 50% reduction in other hypotensive agents was achieved in patients treated with minoxidil and two patients proved resistant to minoxidil, but subsequently responded to oral diazoxide.", "contents": "The treatment of resistant hypertension. Resistant hypertension can be defined in terms of lack of blood pressure response to hypotensive agents, but there may be a big difference between standing and lying blood pressure levels. In general target organ damage and papilloedema improve if the standing blood pressure is controlled; however, progression can occasionally be documented when only the supine blood pressure remains uncontrolled. Resistant hypertension was a frequent phenomenon when ganglion blocking agents and hydrallazine were the only effective hypotensive agents. With the advent of the thiazides, effective control of the blood pressure became the exception rather than the rule; however, it was not until the advent of adrenergic blocking agents that reduction of supine blood pressures was regularly achieved. The addition of hydrallazine or prazosin to a combination of a thiazide and beta-adrenoreceptor blocking agent produces a further significant fall in the blood pressure lying and standing. This combination will control the blood pressure in most patients, but a few remain refractory to maximum doses and will require treatment with oral diazoxide or minoxidil. Both these powerful vasodilators are very effective in resistant hypertension. Oral diazoxide permits excellent control and allows a 10-fold reduction in the doses of other agents. Minoxidil usually needs to be combined with moderate doses of beta-blocking agents to reduce the marked reflex tachycardia. Only a 50% reduction in other hypotensive agents was achieved in patients treated with minoxidil and two patients proved resistant to minoxidil, but subsequently responded to oral diazoxide."}
{"id": "PMID:6255", "title": "Adverse drug reactions during treatment of hypertension.", "content": "Adverse drug reactions (ADRs) can be broadly classified as either \"a nuisance\" or  \"life-threatening\". Voluntary reporting systems gradually accumulate a quite impressive list of suspected ADRs with antihypertensive drugs as their use becomes widespread. Such data gives no clue to true or relative incidence. The absolute and comparative incidence of ADRs can only be determined fairly by a system of unbiased general data collection of ADRs from which the data for antihypertensive drugs is then selected. The Boston Collaborative Drug Surveillance Program provides such a source of information. Data from the Boston Program reveals that most of the listed ADRs with antihypertensive drugs occur very infrequently, that \"nuisance\" ADRs occur in 10 to 29% of patients in whom they are used, and that \"life-threatening\" ADRs occur in less than 1%. ADRs tend to discourage patient compliance with medication aims. In selecting specific antihypertensive therapy the clinician should be mindful not only of the severity of the hypertension to be treated, but also of the nature, type, and severity of potential ADRs, the personality and likely complicance of the patient, and the need for patient education regarding drug effects, possible unwanted effects, and what measures should be taken when ADRs occur.", "contents": "Adverse drug reactions during treatment of hypertension. Adverse drug reactions (ADRs) can be broadly classified as either \"a nuisance\" or  \"life-threatening\". Voluntary reporting systems gradually accumulate a quite impressive list of suspected ADRs with antihypertensive drugs as their use becomes widespread. Such data gives no clue to true or relative incidence. The absolute and comparative incidence of ADRs can only be determined fairly by a system of unbiased general data collection of ADRs from which the data for antihypertensive drugs is then selected. The Boston Collaborative Drug Surveillance Program provides such a source of information. Data from the Boston Program reveals that most of the listed ADRs with antihypertensive drugs occur very infrequently, that \"nuisance\" ADRs occur in 10 to 29% of patients in whom they are used, and that \"life-threatening\" ADRs occur in less than 1%. ADRs tend to discourage patient compliance with medication aims. In selecting specific antihypertensive therapy the clinician should be mindful not only of the severity of the hypertension to be treated, but also of the nature, type, and severity of potential ADRs, the personality and likely complicance of the patient, and the need for patient education regarding drug effects, possible unwanted effects, and what measures should be taken when ADRs occur."}
{"id": "PMID:6257", "title": "[Substituted benzamides].", "content": "The comparison of the therapeutic effects of three molecules belonging to the substituted benzamide family allows the following observations: --the three products are generally well tolerated by the organism; --at sufficient doses they act as a major tranquilizers: -sulpiride is chiefly a disinhibitor but also has antipsychotic properties; -sultopride is at first somewhat sedative, especially when given parenterally, then antipsychotic, and little by little desinhibiting; -GRI 16-65 is \"soothing\", \"euphoriant\", \"sociabilizing\", as well as antipsychotic. Effect of reintegration in reality seems to constitute a common characteristic of these three products.", "contents": "[Substituted benzamides]. The comparison of the therapeutic effects of three molecules belonging to the substituted benzamide family allows the following observations: --the three products are generally well tolerated by the organism; --at sufficient doses they act as a major tranquilizers: -sulpiride is chiefly a disinhibitor but also has antipsychotic properties; -sultopride is at first somewhat sedative, especially when given parenterally, then antipsychotic, and little by little desinhibiting; -GRI 16-65 is \"soothing\", \"euphoriant\", \"sociabilizing\", as well as antipsychotic. Effect of reintegration in reality seems to constitute a common characteristic of these three products."}
{"id": "PMID:6258", "title": "[Study of free and total tryptophan in the plasma. It value in psychiatry].", "content": "The dosage of the whole tryptophan and of the free tryptophan was conducted in 16 normal subjects to establish reference values and in 12 schizophrenic subjects among whom 7 were under treatment and 5 were not. The method of dosage is made by spectrofluorimetry by increasing the native fluorescence of tryptophan. The results give mean values for the free tryptophan and for the ratio of the free tryptophan to the whole tryptophan values that are higher in the schizophrenics than in the normal subjects used as reference, while the whole tryptophan seems to be little modified ; this increase is more noticeable in the schizophrenics under treatment. The limited number of the cases studied does not enable us yet to establish correlations between the increase of the free tryptophan found in some cases and the nature of the schizophrenia, its age and its evolutivity or even the clinical response to the treatment. However, some figures for the free tryptophan being very much higher than the mean value in some schizophrenics, suggest ways of research for understanding the pathogenisis of schizophrenia and the mechanisms of the therapeutic action of the psychotropic drugs.", "contents": "[Study of free and total tryptophan in the plasma. It value in psychiatry]. The dosage of the whole tryptophan and of the free tryptophan was conducted in 16 normal subjects to establish reference values and in 12 schizophrenic subjects among whom 7 were under treatment and 5 were not. The method of dosage is made by spectrofluorimetry by increasing the native fluorescence of tryptophan. The results give mean values for the free tryptophan and for the ratio of the free tryptophan to the whole tryptophan values that are higher in the schizophrenics than in the normal subjects used as reference, while the whole tryptophan seems to be little modified ; this increase is more noticeable in the schizophrenics under treatment. The limited number of the cases studied does not enable us yet to establish correlations between the increase of the free tryptophan found in some cases and the nature of the schizophrenia, its age and its evolutivity or even the clinical response to the treatment. However, some figures for the free tryptophan being very much higher than the mean value in some schizophrenics, suggest ways of research for understanding the pathogenisis of schizophrenia and the mechanisms of the therapeutic action of the psychotropic drugs."}
{"id": "PMID:6259", "title": "Effect of ergoline derivative VUFB-6638 on the adenohypophysial prolactin concentration in rats.", "content": "The compound VUFB-6638 (N-/D-6-methyl-8-isoergolin-I-yl/N'-N'-diethylurea hydrogen maleinate) was administered for four consecutive days to lactating rats in daily oral doses of 0.1, 1.0 and 2.0 mg/kg. The adenohypophysial prolactin concentration decreased by 34% to 68%, respectively. Moreover, this compound reduced or even completely suppressed the lactation. In view of the assumed relations between prolactin and breast carcinoma, a potential use of the drug is noted.", "contents": "Effect of ergoline derivative VUFB-6638 on the adenohypophysial prolactin concentration in rats. The compound VUFB-6638 (N-/D-6-methyl-8-isoergolin-I-yl/N'-N'-diethylurea hydrogen maleinate) was administered for four consecutive days to lactating rats in daily oral doses of 0.1, 1.0 and 2.0 mg/kg. The adenohypophysial prolactin concentration decreased by 34% to 68%, respectively. Moreover, this compound reduced or even completely suppressed the lactation. In view of the assumed relations between prolactin and breast carcinoma, a potential use of the drug is noted."}
{"id": "PMID:6260", "title": "Changes in (3H)leucine incorporation into pineal proteins following estradiol or testosterone administration: involvement of the sympathetic superior cervical ganglion.", "content": "Pineal denervation by superior cervical ganglionectomy (Gx) decreased high affinity binding of estradiol (E2) to the pineal cytosol of female rats and of testosterone to the cytosol of male rats by 40 and 26% and by 75 and 80%, 5 and 14 days after sugery; hormone binding remained unchanged up to 24 h after surgery. Binding to the nuclear fraction decreased sigificantly by 2 weeks after incorporation of (3H) leucine into pineal proteins in Gx. A single injection of E2 (mug) to testosterone propionate (TP) (500 mug) failed to increase the Gx rats when injected 1 or 5 days after surgery. Significant increases were observed in sham-operated controls or in rats subjected to bilateral decentralization of ganglia; however on the 5th day an impairment was observed in hormone ability to enhance [3H]leucine incorporation in decentralized rats. The administration of isoproterenol 19 and 3 h before sacrifice replenished pineal-binding sites for E2 and testosterone in Gx rats, but failed to restore the responsiveness of denervated pineals to hormone administration. Moreover, E2 or TP treatment blocked the increase in labeled amino acid incorporation into proteins brought about by isoproterenol per se. The administration of propranolol 2 and 7 h after hormone injection decreased the ability of E2 and TP to enhance [3H]leucine incorporation by 55 and 41%, respectively. Tyrosine hydroxylase activity of the superior cervical ganglia decreased by 36 and 41% 6 h after E2 or TP administration, and by 43 and 47% after 3 daily injections of the hormones, whereas pineal tyrosine hydroxylase remained unchanged. Hormone treatment for 3 days increased the in vitro uptake of norepinephrine by the ganglia but did not affect uptake in the pineal gland. These data indicate that the integrity of neurons of the superior cervical ganglia is an absolute requirement for E2 and testosterone to enhance [3H]leucine incorporation into pineal proteins in rats.", "contents": "Changes in (3H)leucine incorporation into pineal proteins following estradiol or testosterone administration: involvement of the sympathetic superior cervical ganglion. Pineal denervation by superior cervical ganglionectomy (Gx) decreased high affinity binding of estradiol (E2) to the pineal cytosol of female rats and of testosterone to the cytosol of male rats by 40 and 26% and by 75 and 80%, 5 and 14 days after sugery; hormone binding remained unchanged up to 24 h after surgery. Binding to the nuclear fraction decreased sigificantly by 2 weeks after incorporation of (3H) leucine into pineal proteins in Gx. A single injection of E2 (mug) to testosterone propionate (TP) (500 mug) failed to increase the Gx rats when injected 1 or 5 days after surgery. Significant increases were observed in sham-operated controls or in rats subjected to bilateral decentralization of ganglia; however on the 5th day an impairment was observed in hormone ability to enhance [3H]leucine incorporation in decentralized rats. The administration of isoproterenol 19 and 3 h before sacrifice replenished pineal-binding sites for E2 and testosterone in Gx rats, but failed to restore the responsiveness of denervated pineals to hormone administration. Moreover, E2 or TP treatment blocked the increase in labeled amino acid incorporation into proteins brought about by isoproterenol per se. The administration of propranolol 2 and 7 h after hormone injection decreased the ability of E2 and TP to enhance [3H]leucine incorporation by 55 and 41%, respectively. Tyrosine hydroxylase activity of the superior cervical ganglia decreased by 36 and 41% 6 h after E2 or TP administration, and by 43 and 47% after 3 daily injections of the hormones, whereas pineal tyrosine hydroxylase remained unchanged. Hormone treatment for 3 days increased the in vitro uptake of norepinephrine by the ganglia but did not affect uptake in the pineal gland. These data indicate that the integrity of neurons of the superior cervical ganglia is an absolute requirement for E2 and testosterone to enhance [3H]leucine incorporation into pineal proteins in rats."}
{"id": "PMID:6261", "title": "The effect of bilateral lesions of the ventral noradrenergic bundle on endocrine-induced changes of tyrosine hydroxylase in the rat median eminence.", "content": "With the microdissection method of Palkovits, individual hypothalamic nuclei were removed from the brains of adult male rats, and the tyrosine hydroxylase (TH) activity of each nucleus was determined 7 days after gonadectomy or thyroidectomy. Following gonadectomy, TH activity increased significantly in the median eminence with no change in the periventricular (NPV), arcuate (NARC), and dorsomedial nuclei (NDM), or medial forebrain bundle (MF). Following thyroidectomy, TH activity increased significantly in all 5 hypothalamic nuclei examined. Placement of bilateral lesions in the ventral norepinephrine bundles resulted in a greater than an 85% fall in the dopamine-beta-hydroxylase activity of the median eminence, arcuate nucleus, and ventromedial nucleus, but had no effect on tyrosine hydroxylase activity measured in those same areas. Furthermore, placement of such lesions had no effect on the endocrine-induced increases of TH activity found in the median eminence following gonadectomy and thyroidectomy, but did prevent the increase of TH activity found in the NPV, NDM, and MFB following thyroidectomy. Three conclusions appear to be justified: (a) noradrenergic axons which innervate the median eminence, arcuate, and ventromedial nuclei course in the ventral norepinephrine bundles; (b) the TH content of noradrenergic neurons in the median eminence, arcuate nucleus, and ventromedial nuclei is quite small; and (c) the majority, if not all, of the endocrine-responsive catecholaminergic neurons in the median eminence are dopaminergic.", "contents": "The effect of bilateral lesions of the ventral noradrenergic bundle on endocrine-induced changes of tyrosine hydroxylase in the rat median eminence. With the microdissection method of Palkovits, individual hypothalamic nuclei were removed from the brains of adult male rats, and the tyrosine hydroxylase (TH) activity of each nucleus was determined 7 days after gonadectomy or thyroidectomy. Following gonadectomy, TH activity increased significantly in the median eminence with no change in the periventricular (NPV), arcuate (NARC), and dorsomedial nuclei (NDM), or medial forebrain bundle (MF). Following thyroidectomy, TH activity increased significantly in all 5 hypothalamic nuclei examined. Placement of bilateral lesions in the ventral norepinephrine bundles resulted in a greater than an 85% fall in the dopamine-beta-hydroxylase activity of the median eminence, arcuate nucleus, and ventromedial nucleus, but had no effect on tyrosine hydroxylase activity measured in those same areas. Furthermore, placement of such lesions had no effect on the endocrine-induced increases of TH activity found in the median eminence following gonadectomy and thyroidectomy, but did prevent the increase of TH activity found in the NPV, NDM, and MFB following thyroidectomy. Three conclusions appear to be justified: (a) noradrenergic axons which innervate the median eminence, arcuate, and ventromedial nuclei course in the ventral norepinephrine bundles; (b) the TH content of noradrenergic neurons in the median eminence, arcuate nucleus, and ventromedial nuclei is quite small; and (c) the majority, if not all, of the endocrine-responsive catecholaminergic neurons in the median eminence are dopaminergic."}
{"id": "PMID:6262", "title": "Steroid metabolism in the gonads of a patient with testicular feminization. I. Metabolism of cholesterol, pregnenolone, progesterone and dehydroepiandrosterone in vitro.", "content": "The metabolism of cholesterol-4-14C, pregnenolone-4-14C, progesterone-4-14C and dehydroepiandrosterone-4-14C in a right abdominal and a left inguinal testis of a patient with testicular feminization was studied by a double isotope method in vitro. One of the main metabolites found in all incubations was testosterone. In incubations with cholesterol the delta4-pathway seems to be preferred. The rate of conversion of cholesterol to testosterone in the right testis was 1,27% and in the left testis 4,90%. Pregnenolone was converted to testosterone in the right testis at a rate of 6,61% and in the left testis at a rate of 3,23%. The conversion for testosterone using progesterone as precursor was 13,19% and 3,88% respectively and 11,97% of dehydroepiandrosterone was converted to testosterone in the right testis and 12,32% in the left testis. These findings are compared with data from the literature and conclusions are drawn.", "contents": "Steroid metabolism in the gonads of a patient with testicular feminization. I. Metabolism of cholesterol, pregnenolone, progesterone and dehydroepiandrosterone in vitro. The metabolism of cholesterol-4-14C, pregnenolone-4-14C, progesterone-4-14C and dehydroepiandrosterone-4-14C in a right abdominal and a left inguinal testis of a patient with testicular feminization was studied by a double isotope method in vitro. One of the main metabolites found in all incubations was testosterone. In incubations with cholesterol the delta4-pathway seems to be preferred. The rate of conversion of cholesterol to testosterone in the right testis was 1,27% and in the left testis 4,90%. Pregnenolone was converted to testosterone in the right testis at a rate of 6,61% and in the left testis at a rate of 3,23%. The conversion for testosterone using progesterone as precursor was 13,19% and 3,88% respectively and 11,97% of dehydroepiandrosterone was converted to testosterone in the right testis and 12,32% in the left testis. These findings are compared with data from the literature and conclusions are drawn."}
{"id": "PMID:6265", "title": "Photochemical and biological degradation of water-soluble FWAs.", "content": "A study was made of the photochemical and biological degradation of two water-soluble fluorescent whitening agents (FWAs): the disodium 4,4'-bis(2-sulfostyryl)-biphenyl (1) and the disodium 4,4-bis ([4-anilino-6-(N-methyl-N-2-hydroxyethyl)amino 1,3,5-triazin-2-yl]amino)stilbene-2,2'-disulfonate (2). Each represents an important class of detergent fluorescent whitening agents. The photochemical degradation of (1) was studied by irradiating diluted aqueous solutions of this compound with a low intensity high pressure mercury vapor lamp. From the intermediate, as well as the ultimate photodegradation products isolated, it can be infered that photodegradation of (1) followed the proposed scheme. The biologica degradation of (1) and (2) by activated sludge under aerobic conditions was studied using equipment similar to that proposed by the OECD for determining the biodegradation of anionic synthetic surface active agents. Under the conditons applied, both FWAs were slowly biodegraded, within 30 days, whereas the photodegradation products of (1) were completely biodegraded within 14 days.", "contents": "Photochemical and biological degradation of water-soluble FWAs. A study was made of the photochemical and biological degradation of two water-soluble fluorescent whitening agents (FWAs): the disodium 4,4'-bis(2-sulfostyryl)-biphenyl (1) and the disodium 4,4-bis ([4-anilino-6-(N-methyl-N-2-hydroxyethyl)amino 1,3,5-triazin-2-yl]amino)stilbene-2,2'-disulfonate (2). Each represents an important class of detergent fluorescent whitening agents. The photochemical degradation of (1) was studied by irradiating diluted aqueous solutions of this compound with a low intensity high pressure mercury vapor lamp. From the intermediate, as well as the ultimate photodegradation products isolated, it can be infered that photodegradation of (1) followed the proposed scheme. The biologica degradation of (1) and (2) by activated sludge under aerobic conditions was studied using equipment similar to that proposed by the OECD for determining the biodegradation of anionic synthetic surface active agents. Under the conditons applied, both FWAs were slowly biodegraded, within 30 days, whereas the photodegradation products of (1) were completely biodegraded within 14 days."}
{"id": "PMID:6267", "title": "Characterization of cardiac sarcoplasmic reticulum ATP-ADP phosphate exchange and phosphorylation of the calcium transport adenosine triphosphatase.", "content": "1. The terminal phosphate of (gamma-32P)ATP is rapidly incorporated into cardiac sarcoplasmic reticulum membranes (0.7--1.3 mumol/g protein) in the presence of calcium and magnesium. Cardiac sarcoplasmic reticulum membranes catalize an ATP-ADP phosphate exchange in the presence of calcium and magnesium. 2. Half-maximum activation of the phosphoprotein formation and ATP-ADP phosphate exchange is reached at an ionized calcium concentration of about 0.3 muM. The Hill coefficients are 1.3. 3. Transphosphorylation and ATP-ADP phosphate exchange require magnesium and are maximally activated at magnesium concentrations close to or equal to the ATP concentration. 4. The phosphoprotein level is reduced to about 45% at an ADP/ATP ratio of 0.1. The rate of calcium-dependent ATP splitting declines, whilst the rate of the calcium-dependent ATP-ADP phosphate exchange increases when the ADP/ATP ratio is varied from 0.1 to 1. The sum of both, the rate of ATP splitting and the rate of ADP-ATP phosphate exchange remains constant. 5. Phosphoprotein formation and ATP-ADP phosphate exchange are not affected by azide, dinitrophenol, dicyclohexyl carbodiimide and oubain, whilst both activities are reduced by blockade of -SH groups localized on the outside of the sarcoplasmic reticulum membrane. 6. The isolated phosphoprotein is acid stable. The trichloroacetic acid denatured 32P-labelled membrane complex is dephosphorylated by hydroxylamine, which might indicate that the phosphorylated protein is an acyl-phosphate. 7. Polyacrylamide gel elctrophoresis (performed with phenol/acetic acid/water) of phosphorylated sarcoplasmic reticulum fractions demonstrates that the 32P-incorporation occurs into a protein of about 100000 molecular weight. 8. It is suggested that the phosphoprotein represents a phosphorylated intermediate of the calcium-dependent ATPase which formation occurs as an early step in the reaction sequence of calcium translocation by cardiac sarcoplasmic reticulum similar as in skeletal muscle.", "contents": "Characterization of cardiac sarcoplasmic reticulum ATP-ADP phosphate exchange and phosphorylation of the calcium transport adenosine triphosphatase. 1. The terminal phosphate of (gamma-32P)ATP is rapidly incorporated into cardiac sarcoplasmic reticulum membranes (0.7--1.3 mumol/g protein) in the presence of calcium and magnesium. Cardiac sarcoplasmic reticulum membranes catalize an ATP-ADP phosphate exchange in the presence of calcium and magnesium. 2. Half-maximum activation of the phosphoprotein formation and ATP-ADP phosphate exchange is reached at an ionized calcium concentration of about 0.3 muM. The Hill coefficients are 1.3. 3. Transphosphorylation and ATP-ADP phosphate exchange require magnesium and are maximally activated at magnesium concentrations close to or equal to the ATP concentration. 4. The phosphoprotein level is reduced to about 45% at an ADP/ATP ratio of 0.1. The rate of calcium-dependent ATP splitting declines, whilst the rate of the calcium-dependent ATP-ADP phosphate exchange increases when the ADP/ATP ratio is varied from 0.1 to 1. The sum of both, the rate of ATP splitting and the rate of ADP-ATP phosphate exchange remains constant. 5. Phosphoprotein formation and ATP-ADP phosphate exchange are not affected by azide, dinitrophenol, dicyclohexyl carbodiimide and oubain, whilst both activities are reduced by blockade of -SH groups localized on the outside of the sarcoplasmic reticulum membrane. 6. The isolated phosphoprotein is acid stable. The trichloroacetic acid denatured 32P-labelled membrane complex is dephosphorylated by hydroxylamine, which might indicate that the phosphorylated protein is an acyl-phosphate. 7. Polyacrylamide gel elctrophoresis (performed with phenol/acetic acid/water) of phosphorylated sarcoplasmic reticulum fractions demonstrates that the 32P-incorporation occurs into a protein of about 100000 molecular weight. 8. It is suggested that the phosphoprotein represents a phosphorylated intermediate of the calcium-dependent ATPase which formation occurs as an early step in the reaction sequence of calcium translocation by cardiac sarcoplasmic reticulum similar as in skeletal muscle."}
{"id": "PMID:6268", "title": "Uptake of bromosulfophthalein by isolated liver cells.", "content": "Uptake of the hepatodiagnostic dye bromosulfophthalein into isolated hepatocytes was studied with special regard to the kinetics of transport. The following results were obtained. 1. The uptake of bromosulfophthalein follows Michaelis-Menten kinetics only at low substrate concentrations with an apparent Km=7 +/- 2 muM and V=2.6 +/- 1.7 nmol X mg protein -1 X min -1. At higher bromosulfophthalein concentrations a second mechanism of uptake is observed as indicated by the deviation from linearity in the Lineweaver-Burk plot. 2. The activation energy of uptake was found to be 11 kcal/mol at 10 muM bromosulfophtalein. 3. Uptake is independent of metabolic energy and of the Na+ gradient across the membrane. 4. Taurocholate does not inhibit uptake while indocyanine green inhibits competitively at low bromosulfophthalein concentrations and activates uptake at high bromosulfophthalein concentrations (greater than 20 muM). 5. Amino acid reagents, such as dinitrofluorobenzene, mersalyl, N-ethylmaleimide, and dithionitrobenzene, which modify specific functional groups, did not affect uptake at a concentration of 100 muM.  6. No pH optimum for bromosulfophthalein uptake was observed  in the physiological pH range.  7. Adsorption of bromosulfophthalein to the liver cell membrane has two distinguishable sites with affinities K1=5.7 X 10(-6) M and K2=7 X 10(-5) M and binding capacities n1=1.2 nmol/mg protein and n2=7 nmol/mg protein. Adsorption is inhibited by indocyanine green. The results do not indicate the mediation of bromosulfophthalein uptake by a carrier protein and are consistent with the hypothesis that bromosulfophthalein is bound in an energy-consuming process to a translocating site, possibly in the undissociated form or as ion pair. The consecutive transfer across the membrane appears to require little additional energy.", "contents": "Uptake of bromosulfophthalein by isolated liver cells. Uptake of the hepatodiagnostic dye bromosulfophthalein into isolated hepatocytes was studied with special regard to the kinetics of transport. The following results were obtained. 1. The uptake of bromosulfophthalein follows Michaelis-Menten kinetics only at low substrate concentrations with an apparent Km=7 +/- 2 muM and V=2.6 +/- 1.7 nmol X mg protein -1 X min -1. At higher bromosulfophthalein concentrations a second mechanism of uptake is observed as indicated by the deviation from linearity in the Lineweaver-Burk plot. 2. The activation energy of uptake was found to be 11 kcal/mol at 10 muM bromosulfophtalein. 3. Uptake is independent of metabolic energy and of the Na+ gradient across the membrane. 4. Taurocholate does not inhibit uptake while indocyanine green inhibits competitively at low bromosulfophthalein concentrations and activates uptake at high bromosulfophthalein concentrations (greater than 20 muM). 5. Amino acid reagents, such as dinitrofluorobenzene, mersalyl, N-ethylmaleimide, and dithionitrobenzene, which modify specific functional groups, did not affect uptake at a concentration of 100 muM.  6. No pH optimum for bromosulfophthalein uptake was observed  in the physiological pH range.  7. Adsorption of bromosulfophthalein to the liver cell membrane has two distinguishable sites with affinities K1=5.7 X 10(-6) M and K2=7 X 10(-5) M and binding capacities n1=1.2 nmol/mg protein and n2=7 nmol/mg protein. Adsorption is inhibited by indocyanine green. The results do not indicate the mediation of bromosulfophthalein uptake by a carrier protein and are consistent with the hypothesis that bromosulfophthalein is bound in an energy-consuming process to a translocating site, possibly in the undissociated form or as ion pair. The consecutive transfer across the membrane appears to require little additional energy."}
{"id": "PMID:6269", "title": "Conformation of Escherichia coli glutamic acid tRNA II as studied by hydrogen-tritium exchange catalyzed by cysteine methyl ester.", "content": "Incubation of CMP in 2H2O with 0.5M cysteine methyl ester at p2H 5 and 37 degrees C for 24 h resulted in 43% exchange of 5-H to 5-2H. No deamination of the cytosine nucleus was noted during this treatment. Native and denatured DNA samples from calf thymus were treated in 3H2O with cysteine methyl ester at pH 5 and 37 degrees C for 24 h and incorporation of tritium into each DNA base was determined by enzymic digestion of the treated DNA. The order of the specific radioactivity found was cytosine greater than guanine greater than adenine greater than thymine for denatured DNA and guanine greater than adenine approximately cytosine greater than thymine for native DNA. The ratio of radioactivity for denatured/native was 11.6 for cytosine, 1.5 for guanine, 1.8 for adenine and 1.1 for thymine. Hence the incorporation in cytosine under the reaction conditions is preferential for single-stranded, nonhelical regions of DNA. Escherichia coli glutamic acid tRNA II was treated in 3H2O with 1.24 M cysteine methyl ester at pH 5 and 37 degrees C. The 24-h-treated tRNA was digested with ribonuclease T1 and the fragments were fractionated. Each fragment was then digested with ribonuclease T2 into mononucleotides and the radioactivity distribution among the bases was determined. The average radioactivity found for each of the bases of the four major nucleotides was cytosine greater than guanine approximately adenine greater than uracil. The radioactivity in cytosine varied greatly among the RNase T1 fragments, the ratio of the highest to the lowest radioactivity being 18.7. The corresponding value for guanine was 11.1, for adenine 4.73 and for uracil 3.64. Based on the data obtained, it was deduced that in this tRNA the anticodon loop, the dihydrouridine loop and the extra loop were \"exposed\" under the conditions employed for the labeling. The 5'-terminal cytosine of the anticodon loop was in a \"non-exposed\" state, a situation similar to that previously reported for E. coli tyrosine tRNA [Cashmore, A. R., Brown, D. M. & Smith, J. D. (1971) J. Mol. Biol. 59, 359-373] and for E. coli formylmethionine tRNA [Goddard J. P.+Schulman L. H. (1972) J. Biol. Chem. 247, 3864-3867]. Both cytosine 48, located at the 3'-terminal of the extra loop, and guanine 15 in the dihydrouridine loop were in an \"emposed\" state. This finding does not agree with a tRNA model in which this pair of cytosine and guanine, commonly found in tRNA sequences, forms hydrogen bondings. Positions 30--32, 61--64 and 71, which are located in the stems, were found to be strongly \"buried\".", "contents": "Conformation of Escherichia coli glutamic acid tRNA II as studied by hydrogen-tritium exchange catalyzed by cysteine methyl ester. Incubation of CMP in 2H2O with 0.5M cysteine methyl ester at p2H 5 and 37 degrees C for 24 h resulted in 43% exchange of 5-H to 5-2H. No deamination of the cytosine nucleus was noted during this treatment. Native and denatured DNA samples from calf thymus were treated in 3H2O with cysteine methyl ester at pH 5 and 37 degrees C for 24 h and incorporation of tritium into each DNA base was determined by enzymic digestion of the treated DNA. The order of the specific radioactivity found was cytosine greater than guanine greater than adenine greater than thymine for denatured DNA and guanine greater than adenine approximately cytosine greater than thymine for native DNA. The ratio of radioactivity for denatured/native was 11.6 for cytosine, 1.5 for guanine, 1.8 for adenine and 1.1 for thymine. Hence the incorporation in cytosine under the reaction conditions is preferential for single-stranded, nonhelical regions of DNA. Escherichia coli glutamic acid tRNA II was treated in 3H2O with 1.24 M cysteine methyl ester at pH 5 and 37 degrees C. The 24-h-treated tRNA was digested with ribonuclease T1 and the fragments were fractionated. Each fragment was then digested with ribonuclease T2 into mononucleotides and the radioactivity distribution among the bases was determined. The average radioactivity found for each of the bases of the four major nucleotides was cytosine greater than guanine approximately adenine greater than uracil. The radioactivity in cytosine varied greatly among the RNase T1 fragments, the ratio of the highest to the lowest radioactivity being 18.7. The corresponding value for guanine was 11.1, for adenine 4.73 and for uracil 3.64. Based on the data obtained, it was deduced that in this tRNA the anticodon loop, the dihydrouridine loop and the extra loop were \"exposed\" under the conditions employed for the labeling. The 5'-terminal cytosine of the anticodon loop was in a \"non-exposed\" state, a situation similar to that previously reported for E. coli tyrosine tRNA [Cashmore, A. R., Brown, D. M. & Smith, J. D. (1971) J. Mol. Biol. 59, 359-373] and for E. coli formylmethionine tRNA [Goddard J. P.+Schulman L. H. (1972) J. Biol. Chem. 247, 3864-3867]. Both cytosine 48, located at the 3'-terminal of the extra loop, and guanine 15 in the dihydrouridine loop were in an \"emposed\" state. This finding does not agree with a tRNA model in which this pair of cytosine and guanine, commonly found in tRNA sequences, forms hydrogen bondings. Positions 30--32, 61--64 and 71, which are located in the stems, were found to be strongly \"buried\"."}
{"id": "PMID:6270", "title": "Purification and properties of D-glyceraldehyde-3-phosphate dehydrogenase from an extreme thermophile, Thermus thermophilus strain HB 8.", "content": "1. D-Glyceraldehyde-3-phosphate dehydrogenase from an extreme thermophile, T. thermophilus strain HB8, was purified and crystallized. 2. The enzyme was found to possess remarkable heat stability, being slowly inactivated at 90 degrees C. 3. Basic kinetic constants and pH profile are reported. The enzyme was activated 25-fold by 90 mM NH4Cl, and also by ethanol up to 5-fold at 30 degrees C. 4. The enzyme was found to be far more resistant to urea or sodium dodecylsulfate than the rabbit enzyme. 5. The enzyme was shown to be a tetramer of molecular weight 130000--135000. Amino acid composition analysis revealed no unusual features. Circular dichroic spectra suggested that the contents of the ordered structure of the thermophile enzyme are similar to those of the rabbit enzyme. 6. The other catalytic properties of the thermophile enzyme are discussed in comparison with those of the enzymes from other sources.", "contents": "Purification and properties of D-glyceraldehyde-3-phosphate dehydrogenase from an extreme thermophile, Thermus thermophilus strain HB 8. 1. D-Glyceraldehyde-3-phosphate dehydrogenase from an extreme thermophile, T. thermophilus strain HB8, was purified and crystallized. 2. The enzyme was found to possess remarkable heat stability, being slowly inactivated at 90 degrees C. 3. Basic kinetic constants and pH profile are reported. The enzyme was activated 25-fold by 90 mM NH4Cl, and also by ethanol up to 5-fold at 30 degrees C. 4. The enzyme was found to be far more resistant to urea or sodium dodecylsulfate than the rabbit enzyme. 5. The enzyme was shown to be a tetramer of molecular weight 130000--135000. Amino acid composition analysis revealed no unusual features. Circular dichroic spectra suggested that the contents of the ordered structure of the thermophile enzyme are similar to those of the rabbit enzyme. 6. The other catalytic properties of the thermophile enzyme are discussed in comparison with those of the enzymes from other sources."}
{"id": "PMID:6272", "title": "Effect of pH on the transient reduction of pig-plasma benzylamine oxidase by benzylamine derivatives.", "content": "1. The transient kinetics of reduction of the 470-nm absorption band in benzylamine oxidase by substrate at different pH values between 6 and 10 have been studied by stopped-flow techniques, and substituent effects on kinetic parameters for the reduction process have been examined using a series of ring-substituted benzylamine derivatives as the substrates. 2. Reduction of the enzyme by substrate takes place in two kinetically distinguishable steps, with the intermediate formation of an enzyme-substrate complex in which the substrate appears to be covalently bound through its amino group to the prosthetic group of the enzyme, possibly in the form of an amine-pyridoxal Schiff-base. 3. The apparent stability of the enzyme-substrate complex shows no obvious dependence on the electronic properties of the amine substrates, but is strongly pH-dependent in a way suggesting that substrate-binding involves the non-protonated amines, exclusively, and requires the presence of the acid form of an ionizing group in the enzyme with apparent pKa of 8.8. 4. Reduction of the enzymatic 470-nm chromophore and release of the aldehyde product of the catalytic process are rate-limited by the same monomolecular reaction step involving the enzyme-substrate complex. Rate constants for the rate-limiting reaction exhibit no significant dependence on pH between 6 and 10, but correlate with Hammett sigma-values for the ring-substituted benzylamine derivatives tested, yielding a phi-value of + 0.3.", "contents": "Effect of pH on the transient reduction of pig-plasma benzylamine oxidase by benzylamine derivatives. 1. The transient kinetics of reduction of the 470-nm absorption band in benzylamine oxidase by substrate at different pH values between 6 and 10 have been studied by stopped-flow techniques, and substituent effects on kinetic parameters for the reduction process have been examined using a series of ring-substituted benzylamine derivatives as the substrates. 2. Reduction of the enzyme by substrate takes place in two kinetically distinguishable steps, with the intermediate formation of an enzyme-substrate complex in which the substrate appears to be covalently bound through its amino group to the prosthetic group of the enzyme, possibly in the form of an amine-pyridoxal Schiff-base. 3. The apparent stability of the enzyme-substrate complex shows no obvious dependence on the electronic properties of the amine substrates, but is strongly pH-dependent in a way suggesting that substrate-binding involves the non-protonated amines, exclusively, and requires the presence of the acid form of an ionizing group in the enzyme with apparent pKa of 8.8. 4. Reduction of the enzymatic 470-nm chromophore and release of the aldehyde product of the catalytic process are rate-limited by the same monomolecular reaction step involving the enzyme-substrate complex. Rate constants for the rate-limiting reaction exhibit no significant dependence on pH between 6 and 10, but correlate with Hammett sigma-values for the ring-substituted benzylamine derivatives tested, yielding a phi-value of + 0.3."}
{"id": "PMID:6273", "title": "Alcohol oxidases of Kloeckera sp. and Hansenula polymorpha. Catalytic properties and subunit structures.", "content": "1. Alcohol oxidase (alcohol: oxygen oxidoreductase) of a thermophilic methanol-utilizing yeast, Hansenula polymorpha DL-1, was isolated in crystalline form. 2. This alcohol oxidase of H. polymorpha was more stable to heat than was the enzyme of Kloeckera sp. This difference in heat stability is compatible with the difference in growth temperatures for both yeasts. 3. The crystalline alcohol oxidases of both yeast oxidized the lower primary alcohols (C-2 to C-4) as well as methanol. The apparent Km values for the methanol of Kloeckera and H. polymorpha enzymes were 0.44 and 0.23 mM, respectively. The enzymes could also oxidize formaldehyde to formate, and were inactivated by relatively low concentrations of hydrogen peroxide. 4. The molecular weight for both enzymes was calculated to be about 670000. Each enzyme is composed of eight identical subunits (molecular weight 83000) and contains eight moles of FAD as the prosthetic group. The NH2-terminal and COOH-terminal amino acids of H. polymorpha enzyme were identified as alanine and phenylalanine, respectively. The octameric subunits model of each enzyme was confirmed by electron micrographs, which showed an octad aggregate, composed of two tetragons face to face.", "contents": "Alcohol oxidases of Kloeckera sp. and Hansenula polymorpha. Catalytic properties and subunit structures. 1. Alcohol oxidase (alcohol: oxygen oxidoreductase) of a thermophilic methanol-utilizing yeast, Hansenula polymorpha DL-1, was isolated in crystalline form. 2. This alcohol oxidase of H. polymorpha was more stable to heat than was the enzyme of Kloeckera sp. This difference in heat stability is compatible with the difference in growth temperatures for both yeasts. 3. The crystalline alcohol oxidases of both yeast oxidized the lower primary alcohols (C-2 to C-4) as well as methanol. The apparent Km values for the methanol of Kloeckera and H. polymorpha enzymes were 0.44 and 0.23 mM, respectively. The enzymes could also oxidize formaldehyde to formate, and were inactivated by relatively low concentrations of hydrogen peroxide. 4. The molecular weight for both enzymes was calculated to be about 670000. Each enzyme is composed of eight identical subunits (molecular weight 83000) and contains eight moles of FAD as the prosthetic group. The NH2-terminal and COOH-terminal amino acids of H. polymorpha enzyme were identified as alanine and phenylalanine, respectively. The octameric subunits model of each enzyme was confirmed by electron micrographs, which showed an octad aggregate, composed of two tetragons face to face."}
{"id": "PMID:6274", "title": "Removal of Mn from spinach chloroplasts by sodium cyanide and the binding of Mn2+ to Mn-depleted chloroplasts.", "content": "Manganese and copper were released from spinach chloroplasts by NaCN-treatment, though iron was not affected. The Hill reaction activity was also inhibited by this treatment, but was partially recovered by the addition of either Mn2+ or Cu2+, but not of Fe3+. The interaction of Mn2+ with manganese-depleted chloroplasts by NaCN-treatment was studied using 54Mn2+. A Scatchard plot shows the high and low affinity binding sites of Mn2+ on NaCN-treated chloroplast membrane; high affinity binding being specific for NaCN-treated chloroplast with a binding constant, KH, of 1.9 X 10(5) M-1, and a maximum binding number, NH, of 0.0016 g-atom per mole of chlorophyll. The low binding site was also found on untreated chloroplasts; its binding constant, KL, being 1.2 X 10(4) M-1, and its maximum binding number, NL, of 0.0112 g-atom per mole oc chlorophyll at pH 8.2 NH was proportional to the degree of the removal of Mn by NaCN-treatment and was constant at pH 4--9. NL markedly increased at a high pH with a midpoint of pH 7.9 indicating the exposure of a new, similar binding site. Light illumination partially inhibited the binding of Mn2+. Within 1 min in the dark the binding reaction reached equilibrium in the absence of pyrophosphate, however, 20 min were required to transform into pyrophosphate-resistant form. The pH dependence of the binding of Mn2+ with pKa 7.2 and the ineffectiveness of p-chloromercuribenzoate suggest the possible ligand of Mn2+ is the imidazole nitrogen of the histidine residue.", "contents": "Removal of Mn from spinach chloroplasts by sodium cyanide and the binding of Mn2+ to Mn-depleted chloroplasts. Manganese and copper were released from spinach chloroplasts by NaCN-treatment, though iron was not affected. The Hill reaction activity was also inhibited by this treatment, but was partially recovered by the addition of either Mn2+ or Cu2+, but not of Fe3+. The interaction of Mn2+ with manganese-depleted chloroplasts by NaCN-treatment was studied using 54Mn2+. A Scatchard plot shows the high and low affinity binding sites of Mn2+ on NaCN-treated chloroplast membrane; high affinity binding being specific for NaCN-treated chloroplast with a binding constant, KH, of 1.9 X 10(5) M-1, and a maximum binding number, NH, of 0.0016 g-atom per mole of chlorophyll. The low binding site was also found on untreated chloroplasts; its binding constant, KL, being 1.2 X 10(4) M-1, and its maximum binding number, NL, of 0.0112 g-atom per mole oc chlorophyll at pH 8.2 NH was proportional to the degree of the removal of Mn by NaCN-treatment and was constant at pH 4--9. NL markedly increased at a high pH with a midpoint of pH 7.9 indicating the exposure of a new, similar binding site. Light illumination partially inhibited the binding of Mn2+. Within 1 min in the dark the binding reaction reached equilibrium in the absence of pyrophosphate, however, 20 min were required to transform into pyrophosphate-resistant form. The pH dependence of the binding of Mn2+ with pKa 7.2 and the ineffectiveness of p-chloromercuribenzoate suggest the possible ligand of Mn2+ is the imidazole nitrogen of the histidine residue."}
{"id": "PMID:6275", "title": "Cobalt bovine superoxide dismutase. Reactivity of the cobalt chromophore in the copper-containing and in the copper-free enzyme.", "content": "1. The reactivity of the zinc site of bovine superoxide dismutase has been probed by observing optical and electron paramagnetic resonance changes, under several conditions, of the Co(II)-substituted protein. 2. Only in the absence of copper are the optical and electron paramagnetic resonance spectra of the cobalt chromophore appreciably affected by alkaline pH or by cyanide. With both reagents the reaction with the copper-containing protein appears to involve the water molecule bound to the copper and does not affect the magnetic coupling between copper and cobalt. 3. The reaction of cyanide with the copper-free Co(II) protein leads to a slow detachment of cobalt from the protein as pentacyanocobalt. An oxygen adduct forms in air, analogous to that described in Co(II) carbonic anhydrase (Haffner, P. H. and Coleman, J. E. (1975) J. Biol. Chem. 250, 996--1005.) 4. Acid titration modifies the Co(II) spectra in the same way in the Cu-containing and in the Cu-free protein and brings about uncoupling of the Co(II)--Cu(II) system. Protonation of histidine-61 on the zinc facing nitrogen is suggested. 5. H2O2 modifies the cobalt chromophore only in the presence of copper. Magnetic coupling between Cu(II) and Co(II) seems to be still present after H2O2 inactivation of the enzyme.", "contents": "Cobalt bovine superoxide dismutase. Reactivity of the cobalt chromophore in the copper-containing and in the copper-free enzyme. 1. The reactivity of the zinc site of bovine superoxide dismutase has been probed by observing optical and electron paramagnetic resonance changes, under several conditions, of the Co(II)-substituted protein. 2. Only in the absence of copper are the optical and electron paramagnetic resonance spectra of the cobalt chromophore appreciably affected by alkaline pH or by cyanide. With both reagents the reaction with the copper-containing protein appears to involve the water molecule bound to the copper and does not affect the magnetic coupling between copper and cobalt. 3. The reaction of cyanide with the copper-free Co(II) protein leads to a slow detachment of cobalt from the protein as pentacyanocobalt. An oxygen adduct forms in air, analogous to that described in Co(II) carbonic anhydrase (Haffner, P. H. and Coleman, J. E. (1975) J. Biol. Chem. 250, 996--1005.) 4. Acid titration modifies the Co(II) spectra in the same way in the Cu-containing and in the Cu-free protein and brings about uncoupling of the Co(II)--Cu(II) system. Protonation of histidine-61 on the zinc facing nitrogen is suggested. 5. H2O2 modifies the cobalt chromophore only in the presence of copper. Magnetic coupling between Cu(II) and Co(II) seems to be still present after H2O2 inactivation of the enzyme."}
{"id": "PMID:6276", "title": "Enzymatic synthesis of two fucose-containing glycolipids with fucosyltransferases of human serum.", "content": "Lacto-N-neotetraosylceramide incubated with human serum fucosyltransferase preparations gave rise to two fucoglycolipids. The faster migrating fucoglycolipid I on the basis of its thin-layer chromatographic mobility, susceptibility to alpha(1 leads to 2) fucosidase from Trichomonas foetus, radio-immunoprecipitation with Ulex europeus lectin and studies with Oh (Bombay) sera was identified as H-active glycolipid (H-I). The most probable structure of fucoglycolipid II should be that with fucose linked alpha(1 leads to 3) to N-acetylglucosamine. Lactosylceramide, ceramide trihexoside and globoside were not substrates for human serum fucosyltransferases. Lacto-N-neotetraosyl ceramide served as a fucose acceptor for all serum preparations tested while asialoganglioside was a substrate only when serum preparations containing H-gene dependent alpha-2-L-fucosyltransferase were used. With asialoganglioside only one radioactive reaction product was formed.", "contents": "Enzymatic synthesis of two fucose-containing glycolipids with fucosyltransferases of human serum. Lacto-N-neotetraosylceramide incubated with human serum fucosyltransferase preparations gave rise to two fucoglycolipids. The faster migrating fucoglycolipid I on the basis of its thin-layer chromatographic mobility, susceptibility to alpha(1 leads to 2) fucosidase from Trichomonas foetus, radio-immunoprecipitation with Ulex europeus lectin and studies with Oh (Bombay) sera was identified as H-active glycolipid (H-I). The most probable structure of fucoglycolipid II should be that with fucose linked alpha(1 leads to 3) to N-acetylglucosamine. Lactosylceramide, ceramide trihexoside and globoside were not substrates for human serum fucosyltransferases. Lacto-N-neotetraosyl ceramide served as a fucose acceptor for all serum preparations tested while asialoganglioside was a substrate only when serum preparations containing H-gene dependent alpha-2-L-fucosyltransferase were used. With asialoganglioside only one radioactive reaction product was formed."}
{"id": "PMID:6277", "title": "Properties of prostaglandin synthetase of rabbit kidney medulla.", "content": "The formation in vitro of prostaglandins E2, D2, and F2alpha from arachidonic acid by rabbit kidney medulla homogenate or microsomal fraction is markedly affected by the composition of the incubation medium employed. Optimal biosynthesis is obtained in 0.1 M potassium phosphate buffer, with the optimum pH being 8.0--8.8. Under these conditions prostaglandin formation is linear up to arachidonic acid concentration of 30 muM. The initial rate of formation of prostaglandin E2 + prostaglandin D2 is 3--4 times higher than that of prostaglandin F2alpha. Reduced glutathione (1 mM) did not affect the biosynthesis by medulla homogenate and produced only small stimulation of the biosynthesis by microsomal powder. Hydroquinone produced a small stimulation at a low concentration of 0.005 mM, and a strong inhibition at concentrations of 0.1 mM or higher. Addition of bovine serum albumin (0.1%) reduced the microsomal biosynthesis of prostaglandins by approximately 80%. Addition of boiled homogenate or boiled 140 000 X g supernatant produced small stimulation of microsomal biosynthesis while 140 000 X g supernatant (not boiled) caused small inhibition which was not dose-related. It appears that rabbit kidney prostaglandin-synthetase converts arachidonic acid to prostaglandins E2 and F2alpha in comparable amounts, without apparent need for a cytoplasmic soluble cofactor or specific reducing agents.", "contents": "Properties of prostaglandin synthetase of rabbit kidney medulla. The formation in vitro of prostaglandins E2, D2, and F2alpha from arachidonic acid by rabbit kidney medulla homogenate or microsomal fraction is markedly affected by the composition of the incubation medium employed. Optimal biosynthesis is obtained in 0.1 M potassium phosphate buffer, with the optimum pH being 8.0--8.8. Under these conditions prostaglandin formation is linear up to arachidonic acid concentration of 30 muM. The initial rate of formation of prostaglandin E2 + prostaglandin D2 is 3--4 times higher than that of prostaglandin F2alpha. Reduced glutathione (1 mM) did not affect the biosynthesis by medulla homogenate and produced only small stimulation of the biosynthesis by microsomal powder. Hydroquinone produced a small stimulation at a low concentration of 0.005 mM, and a strong inhibition at concentrations of 0.1 mM or higher. Addition of bovine serum albumin (0.1%) reduced the microsomal biosynthesis of prostaglandins by approximately 80%. Addition of boiled homogenate or boiled 140 000 X g supernatant produced small stimulation of microsomal biosynthesis while 140 000 X g supernatant (not boiled) caused small inhibition which was not dose-related. It appears that rabbit kidney prostaglandin-synthetase converts arachidonic acid to prostaglandins E2 and F2alpha in comparable amounts, without apparent need for a cytoplasmic soluble cofactor or specific reducing agents."}
{"id": "PMID:6278", "title": "Acetyl-CoA carboxylase during development of plastids in wild-type and mutant barley seedlings.", "content": "A soluble acetyl-CoA carboxylase in homogenates of leaves from wild-type barley seedlings was studied. Centrifuging the homogenate at 150,000 X g did not reduce the total activity, but raised the specific activity. During chloroplast development in light-grown seedlings or during light-dependent greening of leaves grown in the dark, both the total activity of the carboxylase per plant and the specific activity per mg of protein in homogenates of the seedlings increased rapidly. The soluble leaf acetyl-CoA carboxylase was studied in a number of barley mutants with lesions in chloroplast development. In a group of three mutants light elicited an increase in acetyl-CoA carboxylase activity as in the wild-type. In two mutants light caused a decrease in activity. Dark-grown leaves of mutant albina-f17 contained levels of soluble acetyl-CoA carboxylase reached only in the light by the wild-type, whereas light-grown albina-f17 seedlings lacked carboxylase activities. The possibility is discussed that leaf cells contain two forms of acetyl-CoA carboxylase, one soluble with unknown location and a dissociable form located in the chloroplast.", "contents": "Acetyl-CoA carboxylase during development of plastids in wild-type and mutant barley seedlings. A soluble acetyl-CoA carboxylase in homogenates of leaves from wild-type barley seedlings was studied. Centrifuging the homogenate at 150,000 X g did not reduce the total activity, but raised the specific activity. During chloroplast development in light-grown seedlings or during light-dependent greening of leaves grown in the dark, both the total activity of the carboxylase per plant and the specific activity per mg of protein in homogenates of the seedlings increased rapidly. The soluble leaf acetyl-CoA carboxylase was studied in a number of barley mutants with lesions in chloroplast development. In a group of three mutants light elicited an increase in acetyl-CoA carboxylase activity as in the wild-type. In two mutants light caused a decrease in activity. Dark-grown leaves of mutant albina-f17 contained levels of soluble acetyl-CoA carboxylase reached only in the light by the wild-type, whereas light-grown albina-f17 seedlings lacked carboxylase activities. The possibility is discussed that leaf cells contain two forms of acetyl-CoA carboxylase, one soluble with unknown location and a dissociable form located in the chloroplast."}
{"id": "PMID:6279", "title": "Calf-spleen nicotinamide--adenine dinucleotide glycohydrolase. Solubilization purification and properties of the enzyme.", "content": "NAD glycohydrolase of calf spleen was solubilized with pancreatic lipase and purified approximatively 800-fold to a specific activity of 7 units/mg of protein by successive DEAE-cellulose and carboxymethyl-cellulose chromatography. The purified enzyme has a molecular weight of 24,000 and is characterized by a double band on disc gel electrophoresis. Some kinetic properties of the NAD-glycohydrolase-catalyzed hydrolsis of NAD have been examined using a titrimetric assay for enzyme activity. The reaction is subject to inhibition be excess of substrate, which disappears at high ionic strength and low pH. At a pH below 5 the kinetic displays an apparent activation by substrate. The effects of pH (4.5-9.0) on the kinetic parameters do not reveal an essential ionizable group in the catalytic process.", "contents": "Calf-spleen nicotinamide--adenine dinucleotide glycohydrolase. Solubilization purification and properties of the enzyme. NAD glycohydrolase of calf spleen was solubilized with pancreatic lipase and purified approximatively 800-fold to a specific activity of 7 units/mg of protein by successive DEAE-cellulose and carboxymethyl-cellulose chromatography. The purified enzyme has a molecular weight of 24,000 and is characterized by a double band on disc gel electrophoresis. Some kinetic properties of the NAD-glycohydrolase-catalyzed hydrolsis of NAD have been examined using a titrimetric assay for enzyme activity. The reaction is subject to inhibition be excess of substrate, which disappears at high ionic strength and low pH. At a pH below 5 the kinetic displays an apparent activation by substrate. The effects of pH (4.5-9.0) on the kinetic parameters do not reveal an essential ionizable group in the catalytic process."}
{"id": "PMID:6280", "title": "N-Acetylbenzotriazole as a protein reagent. Specific behaviour towards delta-chymotrypsin.", "content": "When N-[14C] acetylbenzotriazole, presented here as a new agent for the acetylation of proteins, reacted at pH 8 and 25 degrees C with delta-chymotrypsin, 15 amino groups (the epsilon-amino groups of lysing residues and the alpha-amino terminus of half-cystine-1) and two phenolic groups (those of the two exposed tyrosine residues) were acetylated with respective pseudo first-order constants of 0.056 +/- 0.003 and 0.15 +/- 0.03 min(-1). Surprisingly, in contrast with the acetic anhydride reaction, the alpha-amino group of Ile-16 was found to be not acetylated as shown by N-terminus determination and activity measurements: the modified delta-chymotrypsin (or acetylated delta-chymotrypsin) was fully active after neutral dialysis. Only a transient inactivation due to the incorporation of one [14C] acetyl group per mole of catalytic site was observed. The kinetic constant found for reactivation at pH 8.5 was 0.315 +/- 0.005 min(-1) at 25 degrees C. The enzyme-catalyzed hydrolysis of N-acetylbenzotriazole was described by a k(cat) value of 0.093 +/- 0.005 min(-1) at pH 7 and 25 degrees C. Circular dichroism changes observed at 230 nm during the reaction at pH 8.5, of acetylated delta-chymotrypsin with N-acetylbenzotriazole indicated a total conversion of the amount of enzyme molecules which were in the 'inactive' or 'alkaline' conformation at this pH, into the 'active' or 'neutral' one. Benzotriazole alone was unable to induce such a conformational change. The rate constant of the reverse structural process from the 'neutral' to the 'alkaline' conformation was 0.32 +/- 0.02 min(-1): identical to that of the deacetylation of the catalytic site. Thus, the unusual lack of acetylation of Ile-16 alpha-amino group during delta-chymotrypsin treatment with N-acetylbenzotriazole is interpreted as a stabilization of the enzyme 'neutral' conformation where the Ile-16 alpha-amino group is buried, thus inaccessible to the reagent. The properties of the delta-chymotrypsin modification using N-acetylbenzotriazole led to practical uses: direct spectrophotometric titration of chymotrypsin operational normality at pH 7 and rapid preparation of acetylated delta-chymotrypsin. As a protein reagent, N-acetylbenzotriazole is particularly interesting because of its reactivity towards amino and phenolic groups of amino acid residues, its stability at acid pH, i.e., k(hydrolysis=7.38 X 10(-3) min(-1) at 25 degrees C [Ravaux et al. (1971) Tetrahedron Letters, 4013-4015] and its aromaticity, responsible for optical properties.", "contents": "N-Acetylbenzotriazole as a protein reagent. Specific behaviour towards delta-chymotrypsin. When N-[14C] acetylbenzotriazole, presented here as a new agent for the acetylation of proteins, reacted at pH 8 and 25 degrees C with delta-chymotrypsin, 15 amino groups (the epsilon-amino groups of lysing residues and the alpha-amino terminus of half-cystine-1) and two phenolic groups (those of the two exposed tyrosine residues) were acetylated with respective pseudo first-order constants of 0.056 +/- 0.003 and 0.15 +/- 0.03 min(-1). Surprisingly, in contrast with the acetic anhydride reaction, the alpha-amino group of Ile-16 was found to be not acetylated as shown by N-terminus determination and activity measurements: the modified delta-chymotrypsin (or acetylated delta-chymotrypsin) was fully active after neutral dialysis. Only a transient inactivation due to the incorporation of one [14C] acetyl group per mole of catalytic site was observed. The kinetic constant found for reactivation at pH 8.5 was 0.315 +/- 0.005 min(-1) at 25 degrees C. The enzyme-catalyzed hydrolysis of N-acetylbenzotriazole was described by a k(cat) value of 0.093 +/- 0.005 min(-1) at pH 7 and 25 degrees C. Circular dichroism changes observed at 230 nm during the reaction at pH 8.5, of acetylated delta-chymotrypsin with N-acetylbenzotriazole indicated a total conversion of the amount of enzyme molecules which were in the 'inactive' or 'alkaline' conformation at this pH, into the 'active' or 'neutral' one. Benzotriazole alone was unable to induce such a conformational change. The rate constant of the reverse structural process from the 'neutral' to the 'alkaline' conformation was 0.32 +/- 0.02 min(-1): identical to that of the deacetylation of the catalytic site. Thus, the unusual lack of acetylation of Ile-16 alpha-amino group during delta-chymotrypsin treatment with N-acetylbenzotriazole is interpreted as a stabilization of the enzyme 'neutral' conformation where the Ile-16 alpha-amino group is buried, thus inaccessible to the reagent. The properties of the delta-chymotrypsin modification using N-acetylbenzotriazole led to practical uses: direct spectrophotometric titration of chymotrypsin operational normality at pH 7 and rapid preparation of acetylated delta-chymotrypsin. As a protein reagent, N-acetylbenzotriazole is particularly interesting because of its reactivity towards amino and phenolic groups of amino acid residues, its stability at acid pH, i.e., k(hydrolysis=7.38 X 10(-3) min(-1) at 25 degrees C [Ravaux et al. (1971) Tetrahedron Letters, 4013-4015] and its aromaticity, responsible for optical properties."}
{"id": "PMID:6281", "title": "Exo-beta-N-acetylmuramidase--a novel hexosaminidase. Production by Bacillus subtilis B, purification and characterization.", "content": "Exo-beta-N-acetylmuramidase, or beta-2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-D-glucoside acetamidodeoxyglucohydrolase, is produced by Bacillus subtilis B, growing in a succinate/peptone/salts medium, at the end of exponential growth and occurs partly in the medium and partly bound to the cells. A lysozyme digest of Micrococcus lysodeikticus cell walls, O-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 leads to 4)-2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-D-glucose and O-[2-acetamide-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl]-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose in decreasing order of efficiency, induce the enzyme but O-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose does not do so. The enzyme was purified from the growth medium, after removal of the cells by continuous centrifugation, by ammonium sulphate precipitation, continuous filtration through XM-300 membranes (to remove the high-molecular-weight material which renders the enzyme sedimentable in low-ionic-strength solutions), diafiltration through PM-30 membranes and ion-exchange chromatography on DEAE-Sephadex and CM-Sephadex. Two peaks of activity were obtained. Peak A was purified 1800-fold and was homogenous on polyacrylamide disc gel electrophoresis. A second heterogeneous fraction (peak B) was also collected. Exo-beta-N-acetylmuramidase is most stable at pH 8.0 and has a molecular weight of about 90000. The results of studies on its ability to attack several synthetic and natural substrates are given. The Km and V values for 4-methylumbelliferyl-2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucose and O-[2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl]-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose are respectively 0.19 and 0.65 mM and 1.50 and 16.29 mumol min(-1) mg(-1). From these results and those of inhibition studies it is concluded that the enzyme is specific for substrates with non-reducing N-acetylmuramic acid end groups. Possible roles for this enzyme are discussed.", "contents": "Exo-beta-N-acetylmuramidase--a novel hexosaminidase. Production by Bacillus subtilis B, purification and characterization. Exo-beta-N-acetylmuramidase, or beta-2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-D-glucoside acetamidodeoxyglucohydrolase, is produced by Bacillus subtilis B, growing in a succinate/peptone/salts medium, at the end of exponential growth and occurs partly in the medium and partly bound to the cells. A lysozyme digest of Micrococcus lysodeikticus cell walls, O-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 leads to 4)-2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-D-glucose and O-[2-acetamide-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl]-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose in decreasing order of efficiency, induce the enzyme but O-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose does not do so. The enzyme was purified from the growth medium, after removal of the cells by continuous centrifugation, by ammonium sulphate precipitation, continuous filtration through XM-300 membranes (to remove the high-molecular-weight material which renders the enzyme sedimentable in low-ionic-strength solutions), diafiltration through PM-30 membranes and ion-exchange chromatography on DEAE-Sephadex and CM-Sephadex. Two peaks of activity were obtained. Peak A was purified 1800-fold and was homogenous on polyacrylamide disc gel electrophoresis. A second heterogeneous fraction (peak B) was also collected. Exo-beta-N-acetylmuramidase is most stable at pH 8.0 and has a molecular weight of about 90000. The results of studies on its ability to attack several synthetic and natural substrates are given. The Km and V values for 4-methylumbelliferyl-2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucose and O-[2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl]-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose are respectively 0.19 and 0.65 mM and 1.50 and 16.29 mumol min(-1) mg(-1). From these results and those of inhibition studies it is concluded that the enzyme is specific for substrates with non-reducing N-acetylmuramic acid end groups. Possible roles for this enzyme are discussed."}
{"id": "PMID:6282", "title": "Studies on the active site of yeast hexokinase. Specific phosphorylation of a serine residue induced by D-xylose and ATPMg.", "content": "Yeast hexokinase A(ATP:D-hexose 6-phosphotransferase) is inactivated when incubated in the presence of xylose and ATPMg, or in the presence of D-lyxose in a reaction medium in which ATPMg is being continuously regenerated (phosphoenolpyruvate and pyruvate kinase). The inactivation is due to the phorphorylation of the protein. A linear relationship was observed between the inactivation and the incorporation of 32P from [gamma-32P] ATP. All hexokinase and ATPase activity of the enzyme is lost when one phosphoryl group is incorporated per enzyme subunit (molecular weight 51,000). The phosphoryl group is covalently bound by a ester linkage with a serine residue of the protein.", "contents": "Studies on the active site of yeast hexokinase. Specific phosphorylation of a serine residue induced by D-xylose and ATPMg. Yeast hexokinase A(ATP:D-hexose 6-phosphotransferase) is inactivated when incubated in the presence of xylose and ATPMg, or in the presence of D-lyxose in a reaction medium in which ATPMg is being continuously regenerated (phosphoenolpyruvate and pyruvate kinase). The inactivation is due to the phorphorylation of the protein. A linear relationship was observed between the inactivation and the incorporation of 32P from [gamma-32P] ATP. All hexokinase and ATPase activity of the enzyme is lost when one phosphoryl group is incorporated per enzyme subunit (molecular weight 51,000). The phosphoryl group is covalently bound by a ester linkage with a serine residue of the protein."}
{"id": "PMID:6283", "title": "The transport of S-adenosyl-L-methionine in isolated yeast vacuoles and spheroplasts.", "content": "1. The properties of S-adenosyl-L-methionine accumulating system for both vacuoles and spheroplasts are described. Yeast vacuoles were obtained by a modified metabolic lysis procedure from spheroplasts of Saccharomyces cerevisiae. 2. Isolated vacuoles accumulate S-adenosyl-L-methionine by means of a highly specific transport system as indicated by competition experiments with structural analogs of S-adenosyl-L-methionine. The S-adenosyl-L-methionine transport system shows saturation kinetics with an apparent Km of 68 muM in vacuoles and 11 muM in spheroplasts. 3. S-Adenosyl-L-methionine accumulation into vacuoles does not require glucose, phosphoenolpyruvic acid, ATP, ADP nor any other tri- or di-phosphorylated nucleotides. It is insensitive to azide and 2,4-dinitrophenol which strongly inhibit the glucose-dependent accumulation of S-adenosyl-L-methionine in spheroplasts. 4. The transport of S-adenosyl-L-methionine into vacuoles is optimal at pH 7.4 and is insensitive to nystatin while the uptake of S-adenosyl-L-methionine into spheroplasts is optimal at pH 5.0 and is strongly sensitive to nystatin. On this basis it has thus been possible to measure both the intracytoplasmic and the intravacuolar pool of S-adenosyl-L-methionine. 5. Our results indicate the existence of a highly specific S-adenosyl-L-methionine transport system in the vacuolar membrane which is clearly different from the one present in the plasma membrane of yeast cells.", "contents": "The transport of S-adenosyl-L-methionine in isolated yeast vacuoles and spheroplasts. 1. The properties of S-adenosyl-L-methionine accumulating system for both vacuoles and spheroplasts are described. Yeast vacuoles were obtained by a modified metabolic lysis procedure from spheroplasts of Saccharomyces cerevisiae. 2. Isolated vacuoles accumulate S-adenosyl-L-methionine by means of a highly specific transport system as indicated by competition experiments with structural analogs of S-adenosyl-L-methionine. The S-adenosyl-L-methionine transport system shows saturation kinetics with an apparent Km of 68 muM in vacuoles and 11 muM in spheroplasts. 3. S-Adenosyl-L-methionine accumulation into vacuoles does not require glucose, phosphoenolpyruvic acid, ATP, ADP nor any other tri- or di-phosphorylated nucleotides. It is insensitive to azide and 2,4-dinitrophenol which strongly inhibit the glucose-dependent accumulation of S-adenosyl-L-methionine in spheroplasts. 4. The transport of S-adenosyl-L-methionine into vacuoles is optimal at pH 7.4 and is insensitive to nystatin while the uptake of S-adenosyl-L-methionine into spheroplasts is optimal at pH 5.0 and is strongly sensitive to nystatin. On this basis it has thus been possible to measure both the intracytoplasmic and the intravacuolar pool of S-adenosyl-L-methionine. 5. Our results indicate the existence of a highly specific S-adenosyl-L-methionine transport system in the vacuolar membrane which is clearly different from the one present in the plasma membrane of yeast cells."}
{"id": "PMID:6284", "title": "Enzymic and molecular properties of base-plate parts of bacteriophage P22.", "content": "Using 14C-labeled Salmonella bacterial cells as the substrate, the enzymic and molecular properties of the base-plate parts of phage P22 were studied. The base-plate part consisted of a single protein species which cleaved extensively the O-antigen of Salmonella typhimurium, Salmonelly schottmuellerie and with somewhat slower rate that of Salmonella typhi, releasing oligo-saccharide products with rhamnose at the reducing end. Much less cleavage was observed with a strain of S. typhimurium lysogenic for P22, and no significant reaction with Salmonella anatum, Salmonella newington and Salmonella minneapolis. The base-plate part enzyme was a very heat-stable protein and only 10-20% loss was observed after treatment at 85 degrees C for 5 min. The pH optimum of the enzyme was around 7.5, and the glycosidase activity was not influenced by the ionic strength (25-250 mM( of the medium or the presence of Mg2+. The molecular weight of the base-plate part was 320,000 by sedimentation equilibrium. Dodecylsulphate-acrylamide gel electrophoresis revealed a single band of molecular weight 77,000, indicating that a single base-plate part corresponds to a tetramer of identical subunits. Circular dichroism spectra of P22 base-plate parts showed a major contribution of beta structure. The protein was rich in acidic amino acids, glycine and serine.", "contents": "Enzymic and molecular properties of base-plate parts of bacteriophage P22. Using 14C-labeled Salmonella bacterial cells as the substrate, the enzymic and molecular properties of the base-plate parts of phage P22 were studied. The base-plate part consisted of a single protein species which cleaved extensively the O-antigen of Salmonella typhimurium, Salmonelly schottmuellerie and with somewhat slower rate that of Salmonella typhi, releasing oligo-saccharide products with rhamnose at the reducing end. Much less cleavage was observed with a strain of S. typhimurium lysogenic for P22, and no significant reaction with Salmonella anatum, Salmonella newington and Salmonella minneapolis. The base-plate part enzyme was a very heat-stable protein and only 10-20% loss was observed after treatment at 85 degrees C for 5 min. The pH optimum of the enzyme was around 7.5, and the glycosidase activity was not influenced by the ionic strength (25-250 mM( of the medium or the presence of Mg2+. The molecular weight of the base-plate part was 320,000 by sedimentation equilibrium. Dodecylsulphate-acrylamide gel electrophoresis revealed a single band of molecular weight 77,000, indicating that a single base-plate part corresponds to a tetramer of identical subunits. Circular dichroism spectra of P22 base-plate parts showed a major contribution of beta structure. The protein was rich in acidic amino acids, glycine and serine."}
{"id": "PMID:6285", "title": "Effects of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors.", "content": "The effects of alpha adrenoceptor agonists and antagonists have been examined at pre- and post-synaptically located alpha-adrenoceptors in the pithed rat. The presynaptic receptors were those located at the cardiac sympathetic nerve terminals and the postsynaptic receptors were those present in vascular smooth muscle. Clonidine was approximately equipotent at pre- and post-synaptic alpha-adrenoceptors, whilst LSD and BAY-1470 were more active at the pre- than at post-synaptic sites. Oxymetazoline, naphazoline, methoxamine and phenylephrine were all much more active at the postsynaptic alpha-adrenoceptors. Phentolamine was the most potent antagonist at both pre- and post-synaptic alpha-adrenoceptors. Piperoxan, yohimbine and tolazoline were about 3-7X less potent than phentolamine at both sites. Thymoxamine was about 10X less potent than phentolamine at postsynaptic alpha-adrenoceptors but about 1000X less active at the presynaptic receptors. The differential actions of both agonsists and antagonists at pre- and post-synaptic alpha-adrenoceptors suggest that the receptors may be of different types.", "contents": "Effects of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors. The effects of alpha adrenoceptor agonists and antagonists have been examined at pre- and post-synaptically located alpha-adrenoceptors in the pithed rat. The presynaptic receptors were those located at the cardiac sympathetic nerve terminals and the postsynaptic receptors were those present in vascular smooth muscle. Clonidine was approximately equipotent at pre- and post-synaptic alpha-adrenoceptors, whilst LSD and BAY-1470 were more active at the pre- than at post-synaptic sites. Oxymetazoline, naphazoline, methoxamine and phenylephrine were all much more active at the postsynaptic alpha-adrenoceptors. Phentolamine was the most potent antagonist at both pre- and post-synaptic alpha-adrenoceptors. Piperoxan, yohimbine and tolazoline were about 3-7X less potent than phentolamine at both sites. Thymoxamine was about 10X less potent than phentolamine at postsynaptic alpha-adrenoceptors but about 1000X less active at the presynaptic receptors. The differential actions of both agonsists and antagonists at pre- and post-synaptic alpha-adrenoceptors suggest that the receptors may be of different types."}
{"id": "PMID:6286", "title": "Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels.", "content": "In previous reports, methamphetamine was shown to depress tyrosine hydroxylase (TH) activity in the rat corpus striatum. To evaluate further the mechanism of this decrease in TH activity, enzyme activity was measured in the rat corpus striatum and substantia nigra after repetitive and single-dose methamphetamine administration. Following repeated doses of methamphetamine, nigral TH activity decreased and reached 45% of controls at 12 hr and returned to normal at 60 hr. Striatal TH activity decreased to 40% of control at 36 hr and returned toward normal at 60 hr. When methamphetamine was administered every 6 hr for 30 hr and then discontinued, nigral TH activity returned toward control levels 4 days prior to recovery of striatal TH activity. Methamphetamine initially increased striatal dopamine levels at 6 hr (170% of control). Dopamine levels then decreased in parallel with striatal TH activity but failed to increase as the enzyme recovered. Concurrent administration of chlorpromazine with methamphetamine prevented the methamphetamine-induced decrease in nigral and striatal TH activity and striatal dopamine levels. The results indicate that the methamphetamine-induced depression of striatal and nigral TH activity may be related to increased stimulation of dopamine receptors in the striatum.", "contents": "Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels. In previous reports, methamphetamine was shown to depress tyrosine hydroxylase (TH) activity in the rat corpus striatum. To evaluate further the mechanism of this decrease in TH activity, enzyme activity was measured in the rat corpus striatum and substantia nigra after repetitive and single-dose methamphetamine administration. Following repeated doses of methamphetamine, nigral TH activity decreased and reached 45% of controls at 12 hr and returned to normal at 60 hr. Striatal TH activity decreased to 40% of control at 36 hr and returned toward normal at 60 hr. When methamphetamine was administered every 6 hr for 30 hr and then discontinued, nigral TH activity returned toward control levels 4 days prior to recovery of striatal TH activity. Methamphetamine initially increased striatal dopamine levels at 6 hr (170% of control). Dopamine levels then decreased in parallel with striatal TH activity but failed to increase as the enzyme recovered. Concurrent administration of chlorpromazine with methamphetamine prevented the methamphetamine-induced decrease in nigral and striatal TH activity and striatal dopamine levels. The results indicate that the methamphetamine-induced depression of striatal and nigral TH activity may be related to increased stimulation of dopamine receptors in the striatum."}
{"id": "PMID:6287", "title": "alpha-Adrenoceptors in the ventricular myocardium: clonidine, naphazoline and methoxamine as partial alpha-agonists exerting a competitive dualism in action to phenylephrine.", "content": "Tha alpha-sympathomimetic agonists, clonidine, naphazoline, methoxamine, oxymetazoline and phenylephrine were used to further characterize the alpha-adrenoceptors mediating the positive inotropic effect in the isolated papillary muscle of the rabbit heart. The maximal inotropic effects of these amines were compared with the effect of isoprenaline and it was examined whether or not these amines compete for alpha-adrenoceptors. On the papillary muscle stimulated at 0.5 Hz, phenylephrine showed a high affinity (pD2 value=6.13) and produced the most pronounced intrinsic activity of the alpha-sympathomimetic amines. Therefore, the intrinsic activity of phenylephrine, in the presence of prindolol (3 X 10(-8) M), was used for comparison with those of the other alpha-agonists. Clonidine caused a positive inotropic effect: the intrinsic activity amounted to 0.32 of that of phenylephrine; the affinity was the highest among the amines tested (pD2 value=6.46); its effect was inhibited by 10(-6) M phentolamine. The affinity and the intrinsic activity of naphazoline were slightly lower than those of clonidine. Methoxamine showed a relatively high intrinsic activity (0.56) but the lowest affinity (4.68). Oxymetazoline did not cause any positive inotropic effect. Clonidine, naphazoline and oxymetazoline antagonized the positive inotropic effect of phenylephrine, mediated via the alpha-adrenocaptors in the presence of 3 X 10(-8) M prindolol, in a competitive manner. This observation suggests that these alpha-sympathomimetic amines compete with phenylephrine for the same receptor site. Thus the present results provide additional evidence for alpha-adrenoceptors mediating the positive inotropic actions of sympathomimetic amines in the rabbit papillary muscle.", "contents": "alpha-Adrenoceptors in the ventricular myocardium: clonidine, naphazoline and methoxamine as partial alpha-agonists exerting a competitive dualism in action to phenylephrine. Tha alpha-sympathomimetic agonists, clonidine, naphazoline, methoxamine, oxymetazoline and phenylephrine were used to further characterize the alpha-adrenoceptors mediating the positive inotropic effect in the isolated papillary muscle of the rabbit heart. The maximal inotropic effects of these amines were compared with the effect of isoprenaline and it was examined whether or not these amines compete for alpha-adrenoceptors. On the papillary muscle stimulated at 0.5 Hz, phenylephrine showed a high affinity (pD2 value=6.13) and produced the most pronounced intrinsic activity of the alpha-sympathomimetic amines. Therefore, the intrinsic activity of phenylephrine, in the presence of prindolol (3 X 10(-8) M), was used for comparison with those of the other alpha-agonists. Clonidine caused a positive inotropic effect: the intrinsic activity amounted to 0.32 of that of phenylephrine; the affinity was the highest among the amines tested (pD2 value=6.46); its effect was inhibited by 10(-6) M phentolamine. The affinity and the intrinsic activity of naphazoline were slightly lower than those of clonidine. Methoxamine showed a relatively high intrinsic activity (0.56) but the lowest affinity (4.68). Oxymetazoline did not cause any positive inotropic effect. Clonidine, naphazoline and oxymetazoline antagonized the positive inotropic effect of phenylephrine, mediated via the alpha-adrenocaptors in the presence of 3 X 10(-8) M prindolol, in a competitive manner. This observation suggests that these alpha-sympathomimetic amines compete with phenylephrine for the same receptor site. Thus the present results provide additional evidence for alpha-adrenoceptors mediating the positive inotropic actions of sympathomimetic amines in the rabbit papillary muscle."}
{"id": "PMID:6288", "title": "Competitive oxidation of 6-hydroxydopamine by oxygen and hydrogen peroxide.", "content": "Simultaneous oxygen electrode and conventional polarographic measurements show the net concentration of hydrogen peroxide produced by air oxidation of 6-hydroxydopamine is considerably less than that predicted from the known stoichiometry of the reaction. This is due to competitive oxidation of 6-hydroxydopamine by the generated hydrogen peroxide. The presence of ascorbic acid in this reaction also results in significant decreases of hydrogen peroxide under most conditions. The implications of these results to the molecular mechanism of 6-hydroxydopamine neurotoxicity are discussed.", "contents": "Competitive oxidation of 6-hydroxydopamine by oxygen and hydrogen peroxide. Simultaneous oxygen electrode and conventional polarographic measurements show the net concentration of hydrogen peroxide produced by air oxidation of 6-hydroxydopamine is considerably less than that predicted from the known stoichiometry of the reaction. This is due to competitive oxidation of 6-hydroxydopamine by the generated hydrogen peroxide. The presence of ascorbic acid in this reaction also results in significant decreases of hydrogen peroxide under most conditions. The implications of these results to the molecular mechanism of 6-hydroxydopamine neurotoxicity are discussed."}
{"id": "PMID:6289", "title": "Discriminative stimulus properties of benzodiazepines, barbiturates and pharmacologically related drugs; relation to some intrinsic and anticonvulsant effects.", "content": "Using a food-reinforced two-lever operant method, rats (n = 12) were trained to discriminate chlordiazepoxide (5 mg/kg, p.o.) from solvent (p.o.). With rats trained thus as subjects, generalization experiments were done with various benzodiazepines, barbiturates and related compounds, and with two neuroleptic drugs. The ability of these drugs to induce a discriminative stimulus complex similar to that induced by chlordiazepoxide, was then compared with some intrinsic and anticonvulsant effects of the same drugs. It was found that the discriminative stimulus properties of benzodiazepines, barbiturates, and related compounds correlate with the ability of these drugs to induce ataxia, as well as with part of their anticonvulsant activity. However, the stimulus properties of these drugs, as defined by the procedure described, are based neither on their ataxia-inducing effect, nor on their general depressant or sedative action. It is concluded that these properties constitute a pharmacologically highly specific phenomenon.", "contents": "Discriminative stimulus properties of benzodiazepines, barbiturates and pharmacologically related drugs; relation to some intrinsic and anticonvulsant effects. Using a food-reinforced two-lever operant method, rats (n = 12) were trained to discriminate chlordiazepoxide (5 mg/kg, p.o.) from solvent (p.o.). With rats trained thus as subjects, generalization experiments were done with various benzodiazepines, barbiturates and related compounds, and with two neuroleptic drugs. The ability of these drugs to induce a discriminative stimulus complex similar to that induced by chlordiazepoxide, was then compared with some intrinsic and anticonvulsant effects of the same drugs. It was found that the discriminative stimulus properties of benzodiazepines, barbiturates, and related compounds correlate with the ability of these drugs to induce ataxia, as well as with part of their anticonvulsant activity. However, the stimulus properties of these drugs, as defined by the procedure described, are based neither on their ataxia-inducing effect, nor on their general depressant or sedative action. It is concluded that these properties constitute a pharmacologically highly specific phenomenon."}
{"id": "PMID:6290", "title": "Studies on the centrally mediated hypotensive activity of guanabenz.", "content": "Prior studies demonstrated that guanabenz reduces systemic blood pressure by inhibiting central sympathetic outflow as well as by adrenergic neuron blockade. Potential mechanisms responsible for the reduction of efferent sympathetic activity were examined in the present series. Guanabenz failed to modify carotid sinus nerve activity in a perfused sinus preparation. It reduced sympathetic outflow, heart rate and blood pressure in debuffered cats indicating that its actions are not mediated primarily by baroreceptor mechanisms. alpha-Adrenergic blockade greatly attenuated the response suggesting that the central sympathoinhibitory effect of guanabenz results from alpha-adrenergic receptor activation. Only a high dose of the compound attenuated the increase in sympathetic nerve activity produced by stimulation of the posterior hypothalamus. These experiments lead to the overall conclusion that guanabenz acts primarily at sites which regulate the basal level of sympathetic outflow.", "contents": "Studies on the centrally mediated hypotensive activity of guanabenz. Prior studies demonstrated that guanabenz reduces systemic blood pressure by inhibiting central sympathetic outflow as well as by adrenergic neuron blockade. Potential mechanisms responsible for the reduction of efferent sympathetic activity were examined in the present series. Guanabenz failed to modify carotid sinus nerve activity in a perfused sinus preparation. It reduced sympathetic outflow, heart rate and blood pressure in debuffered cats indicating that its actions are not mediated primarily by baroreceptor mechanisms. alpha-Adrenergic blockade greatly attenuated the response suggesting that the central sympathoinhibitory effect of guanabenz results from alpha-adrenergic receptor activation. Only a high dose of the compound attenuated the increase in sympathetic nerve activity produced by stimulation of the posterior hypothalamus. These experiments lead to the overall conclusion that guanabenz acts primarily at sites which regulate the basal level of sympathetic outflow."}
{"id": "PMID:6291", "title": "Modification and characterization of the permanent sympathectomy produced by the administration of guanethidine to newborn rats.", "content": "The administration of guanethidine to newborn rats has been shown to produce a permanent sympathectomy with potential advantages over immunosympathectomy and 6-hydroxydopamine-induced chemical sympathectomy. In this paper, we report on a revised treatment regimen involving initiation of treatment (50 mg/kg/day) on day 7 after birth and continuing for 3 weeks. Animals treated by this protocol have a low mortality rate (approx. 10% above saline-treated controls) and no permanent growth deficit. Analysis of tyrosine hydroxylase activity in and light microscopic examination of superior cervical ganglia of the guanethidine-treated animals indicate complete destruction of sympathetic neurons by the end of the second week of treatment. During and after treatment there are no decreases in norepinephrine in whole brain of the treated animals. Norepinephrine levels in peripheral tissues are markedly reduced at both 9 and 16 weeks of age. Stimulation of vasomotor outflow produces no increase in blood pressure in guanethidine-treated rats at 9 or 26 weeks of age, indicating a complete and permanent functional denervation of the vasculature. The adrenal glands of the guanethidine-treated animals are not destroyed, but rather respond, apparently by transsynaptic induction, with increases in tyrosine hydroxylase and epinephrine content. Interestingly, despite the continued deprivation of a peripheral sympathetic nervous system in these animals. adrenal tyrosine hydroxylase and epinephrine levels return to control levels by 10 weeks of age. These data indicate that administration of guanethidine to newborn rats produces a very complete and permanent sympathectomy with significant advantages over immunosympathectomy and 6-hydroxydopamine-induced chemical sympathectomy.", "contents": "Modification and characterization of the permanent sympathectomy produced by the administration of guanethidine to newborn rats. The administration of guanethidine to newborn rats has been shown to produce a permanent sympathectomy with potential advantages over immunosympathectomy and 6-hydroxydopamine-induced chemical sympathectomy. In this paper, we report on a revised treatment regimen involving initiation of treatment (50 mg/kg/day) on day 7 after birth and continuing for 3 weeks. Animals treated by this protocol have a low mortality rate (approx. 10% above saline-treated controls) and no permanent growth deficit. Analysis of tyrosine hydroxylase activity in and light microscopic examination of superior cervical ganglia of the guanethidine-treated animals indicate complete destruction of sympathetic neurons by the end of the second week of treatment. During and after treatment there are no decreases in norepinephrine in whole brain of the treated animals. Norepinephrine levels in peripheral tissues are markedly reduced at both 9 and 16 weeks of age. Stimulation of vasomotor outflow produces no increase in blood pressure in guanethidine-treated rats at 9 or 26 weeks of age, indicating a complete and permanent functional denervation of the vasculature. The adrenal glands of the guanethidine-treated animals are not destroyed, but rather respond, apparently by transsynaptic induction, with increases in tyrosine hydroxylase and epinephrine content. Interestingly, despite the continued deprivation of a peripheral sympathetic nervous system in these animals. adrenal tyrosine hydroxylase and epinephrine levels return to control levels by 10 weeks of age. These data indicate that administration of guanethidine to newborn rats produces a very complete and permanent sympathectomy with significant advantages over immunosympathectomy and 6-hydroxydopamine-induced chemical sympathectomy."}
{"id": "PMID:6292", "title": "Studies on the mechanism of the cardiovascualr effects of methyldopa.", "content": "Oral administration of methyldopa (100 mg/kg, twice daily for 3 days) to mongrel dogs produced a significant decrease in blood pressure and heart rate. The drug treatment affected neither the resting venous tone nor the cardiac output. Thus, the hypotensive effect of the drug was predominantly due to a reduction in total peripheral resistance. Vasoconstrictor responses of the renal vasculature to sympathetic nerve stimulation were significantly impaired after methyldopa at all the frequencies, while mesenteric vasoconstrictor responses to sympathetic nerve stimulation were impaired only at the lower stimulation frequencies. In addition, methylnorepinephrine was a significantly less potent vasoconstrictor than norepinephrine in the renal vasculature, but was equipotent to norepinephrine in the mesentery. The finding of a reduction in the renal vascular resistance of methyldopa-treated dogs, with no such alteration in the mesenteric vascular resistance, is consistent with the nerve stimulation studies. Therefore, the results of the present investigation indicate that in addition to the existing evidence favoring a central site of action for methyldopa, the impairment of peripheral sympathetic neuronal function  is also of importance in accounting for the hemodynamic alterations observed following treatment with methyldopa.", "contents": "Studies on the mechanism of the cardiovascualr effects of methyldopa. Oral administration of methyldopa (100 mg/kg, twice daily for 3 days) to mongrel dogs produced a significant decrease in blood pressure and heart rate. The drug treatment affected neither the resting venous tone nor the cardiac output. Thus, the hypotensive effect of the drug was predominantly due to a reduction in total peripheral resistance. Vasoconstrictor responses of the renal vasculature to sympathetic nerve stimulation were significantly impaired after methyldopa at all the frequencies, while mesenteric vasoconstrictor responses to sympathetic nerve stimulation were impaired only at the lower stimulation frequencies. In addition, methylnorepinephrine was a significantly less potent vasoconstrictor than norepinephrine in the renal vasculature, but was equipotent to norepinephrine in the mesentery. The finding of a reduction in the renal vascular resistance of methyldopa-treated dogs, with no such alteration in the mesenteric vascular resistance, is consistent with the nerve stimulation studies. Therefore, the results of the present investigation indicate that in addition to the existing evidence favoring a central site of action for methyldopa, the impairment of peripheral sympathetic neuronal function  is also of importance in accounting for the hemodynamic alterations observed following treatment with methyldopa."}
{"id": "PMID:6293", "title": "Some adrenergic beta-blocking agents affecting lipolysis in human adipose tissue in vitro.", "content": "Antagonistic actions of beta-blocking drugs on isoproterenol-induced lipolysis were studied in human omental adipose tissue. Competitive interaciton characterized by the following pA2 values was found: propranolol 8.7; trimepranol 8.7; practolol 7.1; H 35/25 6.0. The plot of pA2 values of these drugs for human versus rat adipose tissue is linear with slope 2.0 indicating a higher differentiation of beta-antagonist actions in human than in rat adipose tissue.", "contents": "Some adrenergic beta-blocking agents affecting lipolysis in human adipose tissue in vitro. Antagonistic actions of beta-blocking drugs on isoproterenol-induced lipolysis were studied in human omental adipose tissue. Competitive interaciton characterized by the following pA2 values was found: propranolol 8.7; trimepranol 8.7; practolol 7.1; H 35/25 6.0. The plot of pA2 values of these drugs for human versus rat adipose tissue is linear with slope 2.0 indicating a higher differentiation of beta-antagonist actions in human than in rat adipose tissue."}
{"id": "PMID:6296", "title": "[Observation of bacteriophages in wine (author's transl)].", "content": "Electron microscopic examination of samples of Swiss wine, collected during the malolactic fermentation, revealed the presence of bacteriophages of three different morphological types. It is interesting to note that these phages have been found in a product whose pH is lower than 3.5.", "contents": "[Observation of bacteriophages in wine (author's transl)]. Electron microscopic examination of samples of Swiss wine, collected during the malolactic fermentation, revealed the presence of bacteriophages of three different morphological types. It is interesting to note that these phages have been found in a product whose pH is lower than 3.5."}
{"id": "PMID:6297", "title": "Is glutamic acid the pyramidal tract neurotransmitter?", "content": "Applied by microiontophoresis, 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) antagonized excitation by glutamic acid but not by acetylcholine of neurones in the rat cuneate nucleus. HA-966 blocked the short latency excitation of cuneate neurones following stimulation of the pyramidal tract on 28 of 40 cells (70%). Thus, glutamate or a related amino-acid may be the neurotransmitter released by pyramidal tract neurones.", "contents": "Is glutamic acid the pyramidal tract neurotransmitter? Applied by microiontophoresis, 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) antagonized excitation by glutamic acid but not by acetylcholine of neurones in the rat cuneate nucleus. HA-966 blocked the short latency excitation of cuneate neurones following stimulation of the pyramidal tract on 28 of 40 cells (70%). Thus, glutamate or a related amino-acid may be the neurotransmitter released by pyramidal tract neurones."}
{"id": "PMID:6298", "title": "Effects of physalaemin, a vaso-active peptide from amphibian skin, on the excitability of an identifiable molluscan giant neurone of Achatina fulica F\u00e9russac.", "content": "We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia of Achatina fulica F\u00e9russac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone.", "contents": "Effects of physalaemin, a vaso-active peptide from amphibian skin, on the excitability of an identifiable molluscan giant neurone of Achatina fulica F\u00e9russac. We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia of Achatina fulica F\u00e9russac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone."}
{"id": "PMID:6299", "title": "Graft-versus-host reaction and lymphoid organs in normally fed and protein-deprived rats.", "content": "Lymph node graft-versus-host reaction (GVHR) induced by parental splenic lymphocytes inoculated into hind foot pads of F-1 hybrid rats is correlated with the state of the thymus and the spleen of the recipients. This may explain the depression of the reaction after protracted protein deprivation. Furthermore, GVHR provokes mainly in normal rats a reduction of thymus and spleen possibly due to a T-cell transfer to the grafted area.", "contents": "Graft-versus-host reaction and lymphoid organs in normally fed and protein-deprived rats. Lymph node graft-versus-host reaction (GVHR) induced by parental splenic lymphocytes inoculated into hind foot pads of F-1 hybrid rats is correlated with the state of the thymus and the spleen of the recipients. This may explain the depression of the reaction after protracted protein deprivation. Furthermore, GVHR provokes mainly in normal rats a reduction of thymus and spleen possibly due to a T-cell transfer to the grafted area."}
{"id": "PMID:6300", "title": "Cortisone sensitive T-cells in Peyers' patches.", "content": "Pretreatment of donor lymphoid cells with cortisone has been shown to depress the T-cell subpopulation responsible for cellular proliferation in the GVH reaction. A quantitative assay as well as the histological criteria of the GVH reaction have been used in this study to demonstrate the presence of cortisone-sensitive T-cells within the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat.", "contents": "Cortisone sensitive T-cells in Peyers' patches. Pretreatment of donor lymphoid cells with cortisone has been shown to depress the T-cell subpopulation responsible for cellular proliferation in the GVH reaction. A quantitative assay as well as the histological criteria of the GVH reaction have been used in this study to demonstrate the presence of cortisone-sensitive T-cells within the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat."}
{"id": "PMID:6294", "title": "[Detection and quantitative estimation of morphine in the urine of drug addicts by combined 2-dimensional thin-layer chromatography and spectrofluorometry].", "content": "Following extraction from urine and thin-layer bidimensional chromatography, the suspected spot of morphine is located by UV examination at 350 nm and eluted with methanol by means of \"Eluchrom\" apparatus. The dried residue is then subjected to spectrofluorimetric analysis, in definite conditions. This procedure can be used to confirm the identification of the alkaloid and to achieve its estimation. The sensitivity and the recoveries of various quantities of morphine added to urine were determined.", "contents": "[Detection and quantitative estimation of morphine in the urine of drug addicts by combined 2-dimensional thin-layer chromatography and spectrofluorometry]. Following extraction from urine and thin-layer bidimensional chromatography, the suspected spot of morphine is located by UV examination at 350 nm and eluted with methanol by means of \"Eluchrom\" apparatus. The dried residue is then subjected to spectrofluorimetric analysis, in definite conditions. This procedure can be used to confirm the identification of the alkaloid and to achieve its estimation. The sensitivity and the recoveries of various quantities of morphine added to urine were determined."}
{"id": "PMID:6301", "title": "[Comparative evaluation of the antitoxic activity of central nervous system analeptics and their combinations in barbamyl poisoning].", "content": "Tests conducted on rats poisoned with increasingly lethal doses of sodium amytal demonstrated the antitoxic activity of an analeptic mixture to be superior to that of picrotoxin, strichnine, corasol and caffeine entering into its composition and also to the activity of bemegride. As to the degree of antitoxic activity in poisoning of mice with sodium amytal (one LD50) the CNS analeptics are arranged in the following descending oder of their action: analeptic mixture, picrotoxin, bemegride, corasol, strychnine. In poisoning with higher doses of sodium amytal (LD84) corasol, strychnine and caffeine are ineffective, the most productive being analeptic mixture and picrotoxin. Bemegride proves effective only in a single dose of 2.8 LD50 for intact animals.", "contents": "[Comparative evaluation of the antitoxic activity of central nervous system analeptics and their combinations in barbamyl poisoning]. Tests conducted on rats poisoned with increasingly lethal doses of sodium amytal demonstrated the antitoxic activity of an analeptic mixture to be superior to that of picrotoxin, strichnine, corasol and caffeine entering into its composition and also to the activity of bemegride. As to the degree of antitoxic activity in poisoning of mice with sodium amytal (one LD50) the CNS analeptics are arranged in the following descending oder of their action: analeptic mixture, picrotoxin, bemegride, corasol, strychnine. In poisoning with higher doses of sodium amytal (LD84) corasol, strychnine and caffeine are ineffective, the most productive being analeptic mixture and picrotoxin. Bemegride proves effective only in a single dose of 2.8 LD50 for intact animals."}
{"id": "PMID:6302", "title": "[Effect of 1,4-benzodiazepine derivatives on the toxic action of oxygen under increased pressure].", "content": "The 1,4-benzodiazepine derivatives (diazepam, nitrazepm, lorazepam, clonazepam and two newly synthetized compounds of this series) increase the resistance of albino rats and rabbits to the toxic effect of oxygen under high pressure (7 and 5.5 atm respectively). The compounds under study are apt to avert over a long period the development of metabolic acidosis which appears following the action of high-pressure oxygen on the body.", "contents": "[Effect of 1,4-benzodiazepine derivatives on the toxic action of oxygen under increased pressure]. The 1,4-benzodiazepine derivatives (diazepam, nitrazepm, lorazepam, clonazepam and two newly synthetized compounds of this series) increase the resistance of albino rats and rabbits to the toxic effect of oxygen under high pressure (7 and 5.5 atm respectively). The compounds under study are apt to avert over a long period the development of metabolic acidosis which appears following the action of high-pressure oxygen on the body."}
{"id": "PMID:6304", "title": "[Effect of noninhalant anesthetics on the conduction of excitation in the ventrolateral columns of the cat spinal cord].", "content": "Acute tests on spinal cats were set up to enquire into the effect produced by sodium oxybutyrate, hexobarbital sodium and viadril used in anesthetic doses on the evoked responses in the ventrolateral columns of the spinal cord following stimulation of the skin and pelvic nerves with single and paired stimuli at an interval of 100 msec. Sodium oxybutyrate forces the amplitude of both the evoked responses after the paired stimulation below the initial level by 40-70 per cent. Hexobarbital sodium and viadril, without changing noticeably the amplitude of the first response, are instrumental in reducing the second one by as much as 30-40 per cent. The responses obtained on stimulation of the pelvic nerve are more sensitive to the test substances than are those evoked by the stimulation of the skin nerve.", "contents": "[Effect of noninhalant anesthetics on the conduction of excitation in the ventrolateral columns of the cat spinal cord]. Acute tests on spinal cats were set up to enquire into the effect produced by sodium oxybutyrate, hexobarbital sodium and viadril used in anesthetic doses on the evoked responses in the ventrolateral columns of the spinal cord following stimulation of the skin and pelvic nerves with single and paired stimuli at an interval of 100 msec. Sodium oxybutyrate forces the amplitude of both the evoked responses after the paired stimulation below the initial level by 40-70 per cent. Hexobarbital sodium and viadril, without changing noticeably the amplitude of the first response, are instrumental in reducing the second one by as much as 30-40 per cent. The responses obtained on stimulation of the pelvic nerve are more sensitive to the test substances than are those evoked by the stimulation of the skin nerve."}
{"id": "PMID:6305", "title": "[Neuromediator content in the synaptic vesicles of rat adrenergic nerves in some pharmacological actions].", "content": "Cytochemical electron microscopy was employed to study the content of neurotransmitters in the synaptic vesicles of adrenergic nerve fibers of Vas deferens of the rat following depletion of the meadiator's reserves by tyramine and subsequent accumulation of exogenous norepinephrine. Subject to investigation was also the effect of antidepressants (phthoracizine and imipramine) on the accumulation of exogenous norepinephrine in the synaptic vesicles. Phthoracizine and imipramine (1 and 10 gamma/ml) are shown to block the acculation of norepinephrine in the vesicles, when the mediator is introduced in a concentration of 0,5 gamma/ml, and not to impede this process, if the mediator's concentration is increased to 30 gamma/ml.", "contents": "[Neuromediator content in the synaptic vesicles of rat adrenergic nerves in some pharmacological actions]. Cytochemical electron microscopy was employed to study the content of neurotransmitters in the synaptic vesicles of adrenergic nerve fibers of Vas deferens of the rat following depletion of the meadiator's reserves by tyramine and subsequent accumulation of exogenous norepinephrine. Subject to investigation was also the effect of antidepressants (phthoracizine and imipramine) on the accumulation of exogenous norepinephrine in the synaptic vesicles. Phthoracizine and imipramine (1 and 10 gamma/ml) are shown to block the acculation of norepinephrine in the vesicles, when the mediator is introduced in a concentration of 0,5 gamma/ml, and not to impede this process, if the mediator's concentration is increased to 30 gamma/ml."}
{"id": "PMID:6306", "title": "[Effect of some phenothiazine derivatives on kidney function].", "content": "Chlorathizin and Chlormorphathizin are shown to exercise in 24-hours long tests a substantial diuretic and saluretic action on rats and dogs. Fluorathizin, as well as imizine inhibited the urinary flow. Diprazine augmented the urinary output in dogs, but depressed it in rats. The new antidepressive drug azaphen did not have any marked effect on the urinary flow.", "contents": "[Effect of some phenothiazine derivatives on kidney function]. Chlorathizin and Chlormorphathizin are shown to exercise in 24-hours long tests a substantial diuretic and saluretic action on rats and dogs. Fluorathizin, as well as imizine inhibited the urinary flow. Diprazine augmented the urinary output in dogs, but depressed it in rats. The new antidepressive drug azaphen did not have any marked effect on the urinary flow."}
{"id": "PMID:6303", "title": "[Effect of psychotropic and anticonvulsive preparations on transport ATPase in the renal tubules of the guinea pig].", "content": "The effect of 4 groups of medicamentous agents, viz. neoruleptics, tricyclic antidepressants, somnifacients and antiepileptics - on the activity of the transport ATPase and p-nitrophenylphosphatase from the renal tubules of the guinea pig was studied. Used in high concentrations neuroleptics suppress almost completely the activity of the enzyme, but in small doses influence but little that of the p-nitrophenylphosphatase. The butyrophenone derivatives have a mild effect upon the activity of the p-nitrophenylphosphatase and in low concentrations they stimulate it. The effect of tricyclic antidepressants closely approaches the one produced by neuroleptics-phenothiazines. Lithium carbonate leaves the enzyme intact. Barbiturates and antiepileptic agents inhibit but feebly these enzymes.", "contents": "[Effect of psychotropic and anticonvulsive preparations on transport ATPase in the renal tubules of the guinea pig]. The effect of 4 groups of medicamentous agents, viz. neoruleptics, tricyclic antidepressants, somnifacients and antiepileptics - on the activity of the transport ATPase and p-nitrophenylphosphatase from the renal tubules of the guinea pig was studied. Used in high concentrations neuroleptics suppress almost completely the activity of the enzyme, but in small doses influence but little that of the p-nitrophenylphosphatase. The butyrophenone derivatives have a mild effect upon the activity of the p-nitrophenylphosphatase and in low concentrations they stimulate it. The effect of tricyclic antidepressants closely approaches the one produced by neuroleptics-phenothiazines. Lithium carbonate leaves the enzyme intact. Barbiturates and antiepileptic agents inhibit but feebly these enzymes."}
{"id": "PMID:6312", "title": "Drugs and brain mitochondrial enzymatic activities during post-natal development in rat.", "content": "The enzymatic activities of two mitochondrial enzymes, i.e. succinate dehydrogenase and NADH-cytochrome c reductase were investigated in the brain of rats at different stages of post-natal development. In addition, the effect of the pharmacological treatment with two drugs, nicergoline and bamethan, able to interact with the alpha or the beta receptors respectively, was evaluated. The results show that both the enzymatic activities rapidly increase in the first days of extra-uterine life, thus indicating an adaptation of mitochondrial oxidative processes to post-natal environmental conditions. The pharmacological treatment with the two drugs does not induce any changes in the enzymatic activities tested.", "contents": "Drugs and brain mitochondrial enzymatic activities during post-natal development in rat. The enzymatic activities of two mitochondrial enzymes, i.e. succinate dehydrogenase and NADH-cytochrome c reductase were investigated in the brain of rats at different stages of post-natal development. In addition, the effect of the pharmacological treatment with two drugs, nicergoline and bamethan, able to interact with the alpha or the beta receptors respectively, was evaluated. The results show that both the enzymatic activities rapidly increase in the first days of extra-uterine life, thus indicating an adaptation of mitochondrial oxidative processes to post-natal environmental conditions. The pharmacological treatment with the two drugs does not induce any changes in the enzymatic activities tested."}
{"id": "PMID:6307", "title": "[Comparative characteristics of fluorasizine metabolism in different species of animals and man].", "content": "The process of phthoracizine (10-(beta-diethylaminopropiniol)-2-triphthormethylphenothiazine hydrochloride) transformation proceeding in various animal species and in man is similar in grosso modo to biotransformation of chlorpromazine and of compounds related to the latter, including sulphoxidation, dealkylation in the side chain nitrogen, hydroxylation, glucoronoconjugation and the formation of products with the side chain degradation. At the same time, one can note a difference which finds its expression in the development of a large quantity of the phthoracizine metabolites attended by destruction of the side chain, as well as of hydroxylated sulphoxidated products of its transformation. In rats, more than in rabbits and mice, the spectrum of the phthoracizine metabolites is closer to the products of its biotransformation passed with the human urine.", "contents": "[Comparative characteristics of fluorasizine metabolism in different species of animals and man]. The process of phthoracizine (10-(beta-diethylaminopropiniol)-2-triphthormethylphenothiazine hydrochloride) transformation proceeding in various animal species and in man is similar in grosso modo to biotransformation of chlorpromazine and of compounds related to the latter, including sulphoxidation, dealkylation in the side chain nitrogen, hydroxylation, glucoronoconjugation and the formation of products with the side chain degradation. At the same time, one can note a difference which finds its expression in the development of a large quantity of the phthoracizine metabolites attended by destruction of the side chain, as well as of hydroxylated sulphoxidated products of its transformation. In rats, more than in rabbits and mice, the spectrum of the phthoracizine metabolites is closer to the products of its biotransformation passed with the human urine."}
{"id": "PMID:6309", "title": "[Effect of analgestics and narcotics on the potentials of the posterior roots evoked by stimulation of the sensorimotor cortex].", "content": "Experiments set up on unanesthetized, curarized cats demonstrated that sodium oxybutyrate in doses of 75--200 mg/kg and nembutal in doses of 5--20 mg/kg prolong the duration of corticospinal posterior roots potentials (PRP). The initial effect of morphine and promedol in doses of 1--3 and 0.5--1 mg/kg, respectively was not only a longer duration (by 30--40 msec), but also a higher amplitude of the PRP, evoked by the stimulation of the sensomotor cortex. Phentanyl used in a dose range of 0.01 to 0.06 mg/kg did not produce any changes in the descending PRP. Anesthetics (sodium oxybutyrate, nembutal, ether) and analgesics (morphine, phenadon) inhibited the corticospinal PRP, when used in large doses.", "contents": "[Effect of analgestics and narcotics on the potentials of the posterior roots evoked by stimulation of the sensorimotor cortex]. Experiments set up on unanesthetized, curarized cats demonstrated that sodium oxybutyrate in doses of 75--200 mg/kg and nembutal in doses of 5--20 mg/kg prolong the duration of corticospinal posterior roots potentials (PRP). The initial effect of morphine and promedol in doses of 1--3 and 0.5--1 mg/kg, respectively was not only a longer duration (by 30--40 msec), but also a higher amplitude of the PRP, evoked by the stimulation of the sensomotor cortex. Phentanyl used in a dose range of 0.01 to 0.06 mg/kg did not produce any changes in the descending PRP. Anesthetics (sodium oxybutyrate, nembutal, ether) and analgesics (morphine, phenadon) inhibited the corticospinal PRP, when used in large doses."}
{"id": "PMID:6310", "title": "[Effect of narcotic analgesics on the cortical control process of impulse transmission in the afferent pathways of the sciatic nerve].", "content": "The effect produced by narcotic analgetics with their intravenous administration on the process of cortical control over the transmission of impulses along specific routes of the sciatic nerve was studied. The conditioning stimulation of the cortex was effected by using a monopolar electrode through single electric impulses. The interval between conditioning and test (on sciatic nerve) impulses was of 80-120 ms. Morphine (1-2 mg/kg), promedol (trimeperidin) (1-2 mg/kg) and phentanyl (100 gamma/kg) potentiated the inhibition of evoked potentials in the nucleus gracilis and in VPL, observed upon stimulation of the cortex of optic lobuses. The intensification of inhibitory corticifugal mechanisms occurring under the effect of narcotic analgetics takes place both on the level of the medulla oblongata and of the thalamic one.", "contents": "[Effect of narcotic analgesics on the cortical control process of impulse transmission in the afferent pathways of the sciatic nerve]. The effect produced by narcotic analgetics with their intravenous administration on the process of cortical control over the transmission of impulses along specific routes of the sciatic nerve was studied. The conditioning stimulation of the cortex was effected by using a monopolar electrode through single electric impulses. The interval between conditioning and test (on sciatic nerve) impulses was of 80-120 ms. Morphine (1-2 mg/kg), promedol (trimeperidin) (1-2 mg/kg) and phentanyl (100 gamma/kg) potentiated the inhibition of evoked potentials in the nucleus gracilis and in VPL, observed upon stimulation of the cortex of optic lobuses. The intensification of inhibitory corticifugal mechanisms occurring under the effect of narcotic analgetics takes place both on the level of the medulla oblongata and of the thalamic one."}
{"id": "PMID:6308", "title": "[Effect of adrenergic compounds on the brain potentials evoked by stimulation of the dental pulp].", "content": "Intraventriculare injections have brough evidence that alpha-adrenomimetic norepinephrine and beta-adrenomimetic isopropylnorepinephrine augment in the senso-motor region of the cortex the amplitude of primary responses evoked through a dental pulp stimulation. The alpha-adrenoblocking agents--dihydroergotoxin and phentolamine and the beta-edrenoblocking agent propranolol force down the amplitude of primary responses. The sphere of the drugs action is presumed to be the thalamic nuclei.", "contents": "[Effect of adrenergic compounds on the brain potentials evoked by stimulation of the dental pulp]. Intraventriculare injections have brough evidence that alpha-adrenomimetic norepinephrine and beta-adrenomimetic isopropylnorepinephrine augment in the senso-motor region of the cortex the amplitude of primary responses evoked through a dental pulp stimulation. The alpha-adrenoblocking agents--dihydroergotoxin and phentolamine and the beta-edrenoblocking agent propranolol force down the amplitude of primary responses. The sphere of the drugs action is presumed to be the thalamic nuclei."}
{"id": "PMID:6311", "title": "[Effect of izadrin, inderal and netalid on the periodic activity of the rabbit myometrium].", "content": "The contractility of an isolated rabbit uterus was studied. It was found that when used in low concentrations (1.10(-9)-1.10(-7) g/ml) isoprenaline, while stimulating the beta-adrenoreceptors of the uterus, inhibits its contractions, whereas in high concentrations (1.10(6)-1.10(-5) g/ml) it is capable of intensifying uterine contractions owing to stimulation of the uterine alpha-adrenoreceptors. Dihydroergotoxin (1.10(-6) g/ml), a blocking agent of alpha-adrenoreceptors, averts and eliminates the stimulating effect of isoprenaline on the uterus. Propranolol and netalide, blocking agents of the beta-adrenoreceptors, abolish the already developed depressing action of isoprenaline on the contractile activity of the uterus, but fail to prevent this effect with their preliminary application.", "contents": "[Effect of izadrin, inderal and netalid on the periodic activity of the rabbit myometrium]. The contractility of an isolated rabbit uterus was studied. It was found that when used in low concentrations (1.10(-9)-1.10(-7) g/ml) isoprenaline, while stimulating the beta-adrenoreceptors of the uterus, inhibits its contractions, whereas in high concentrations (1.10(6)-1.10(-5) g/ml) it is capable of intensifying uterine contractions owing to stimulation of the uterine alpha-adrenoreceptors. Dihydroergotoxin (1.10(-6) g/ml), a blocking agent of alpha-adrenoreceptors, averts and eliminates the stimulating effect of isoprenaline on the uterus. Propranolol and netalide, blocking agents of the beta-adrenoreceptors, abolish the already developed depressing action of isoprenaline on the contractile activity of the uterus, but fail to prevent this effect with their preliminary application."}
{"id": "PMID:6326", "title": "Studies of human transcortin at different pHs: circular dichroism, polymerisation and binding affinity.", "content": "The transcortin we have used in this work is extremely pure. This was shown by the polymerisation observed at pH 4. This polymerisation is never observed with an impure form of transcortin [4]. Moreover, since it is known that the presence of cortisol in the binding site is an essential condition to the activity of purified transcortin [5], it appears that a correlation between the secondary structure and the biological activity of the transcortin exists. The results we have obtained are summarized below: (1) The inhibition of the transcortin binding capacity essentially takes place between pH 5 and 4. (2) A reorganisation of the structure of the protein moiety is observed between pH 6.5 and 5.9. (3) A decrease of the helicity ratio is observed between pH 5 and 4. It appears therefore that, in the limits of experimental accuracy of CD measurements to determine the amount of beta-structure, no appreciable change of binding activity is taking place after the appearance of a large percentage of beta-structure between pH 6.5 and 6. On the other hand, the sudden decrease of protein activity at low pH is likely to be correlated with the disappearance of a well-defined helical region. Other biochemical and physical experiments would be of course necessary, in order to precise this first observation of a structure-function relationship in transcortin.", "contents": "Studies of human transcortin at different pHs: circular dichroism, polymerisation and binding affinity. The transcortin we have used in this work is extremely pure. This was shown by the polymerisation observed at pH 4. This polymerisation is never observed with an impure form of transcortin [4]. Moreover, since it is known that the presence of cortisol in the binding site is an essential condition to the activity of purified transcortin [5], it appears that a correlation between the secondary structure and the biological activity of the transcortin exists. The results we have obtained are summarized below: (1) The inhibition of the transcortin binding capacity essentially takes place between pH 5 and 4. (2) A reorganisation of the structure of the protein moiety is observed between pH 6.5 and 5.9. (3) A decrease of the helicity ratio is observed between pH 5 and 4. It appears therefore that, in the limits of experimental accuracy of CD measurements to determine the amount of beta-structure, no appreciable change of binding activity is taking place after the appearance of a large percentage of beta-structure between pH 6.5 and 6. On the other hand, the sudden decrease of protein activity at low pH is likely to be correlated with the disappearance of a well-defined helical region. Other biochemical and physical experiments would be of course necessary, in order to precise this first observation of a structure-function relationship in transcortin."}
{"id": "PMID:6340", "title": "Cryptorchidism in the subfertile male.", "content": "Certain conclusions may be drawn from the present review and presentation of new data concerning the unilaterally cryptorchid patient and possible subfertility: 1. The truly undescended testis--not the retractile testis of infancy--will not descend spontaneously after 1 year of age. 2. The seminal quality of the unilaterally cryptorchid patient is definitely impaired, although not rendered infertile, in a great majority of patients irrespective of the time of surgery. 3. The dystopic position of the maldescended testis appears to superimpose a second insult on what very likely may be an inherent abnormality in the cryptorchid testis, the latter accounting, perhaps, for its abnormal extrascrotal position. 4. Orchiopexy before the age of 5 seems advisable to ensure minimal histologic changes that may be secondary to the testis' increased exposure to elevated extrascrotal temperature. 5. The cryptorchid testis will be smaller in size irrespective of surgery, and usually correlates with significant testicular pathology. 6. Basal levels of gonadotropins, especially follicle-stimulating hormone, are likely to be elevated, but this does not necessarily imply overwhelming testicular damage. Androgen production should not be affected. 7. Surgical correction is advised when human chorionic gonadotropin stimulation fails to produce teticular descent, thereby defining the maldescended testis as not merely retractile but truly \"crytorchid.\"", "contents": "Cryptorchidism in the subfertile male. Certain conclusions may be drawn from the present review and presentation of new data concerning the unilaterally cryptorchid patient and possible subfertility: 1. The truly undescended testis--not the retractile testis of infancy--will not descend spontaneously after 1 year of age. 2. The seminal quality of the unilaterally cryptorchid patient is definitely impaired, although not rendered infertile, in a great majority of patients irrespective of the time of surgery. 3. The dystopic position of the maldescended testis appears to superimpose a second insult on what very likely may be an inherent abnormality in the cryptorchid testis, the latter accounting, perhaps, for its abnormal extrascrotal position. 4. Orchiopexy before the age of 5 seems advisable to ensure minimal histologic changes that may be secondary to the testis' increased exposure to elevated extrascrotal temperature. 5. The cryptorchid testis will be smaller in size irrespective of surgery, and usually correlates with significant testicular pathology. 6. Basal levels of gonadotropins, especially follicle-stimulating hormone, are likely to be elevated, but this does not necessarily imply overwhelming testicular damage. Androgen production should not be affected. 7. Surgical correction is advised when human chorionic gonadotropin stimulation fails to produce teticular descent, thereby defining the maldescended testis as not merely retractile but truly \"crytorchid.\""}
{"id": "PMID:6342", "title": "[Participation of the genetic apparatus in memory and learning phenomena].", "content": "The first series of experiments showed that inhibition of the proteins synthesis followed by memory disorders, was reflected in decrease of the synaptosomal proteins fraction which was identified as the cholinoreceptor protein. Another series of experiments: training of rats to use unpreferred paw, showed the system acetylcholine-acetylcholinesterase to be directly connected with memory phenomena, and the synthesis of this enzyme to be induced by genetic apparatus. The third series of experiments showed that feeding of rats with small doses of aminoacids for a long time leads to regular shifts in distribution of both the aminoacids and the monoamines. The aminoacids increasing the brain activity were found to activate the production of cycle-adenyl acid. Those aminoacids which inhibit the brain activity, decrease the production of cyclic-AMP. Tranquilizers which decrease the level of monoamines and inhibit the brain activity, also decrease the production of cyclic-AMP. Antidepressants inhibiting MAO and increasing the level of monoamines in the brain, activate the production of cyclic-AMP. As the monoamines act via cyclic-AMP and the latter participates in suppression of DNA, the mechanism of involvement of the genetic apparatus in regulation of memory phenomena and learning, becomes more apparent.", "contents": "[Participation of the genetic apparatus in memory and learning phenomena]. The first series of experiments showed that inhibition of the proteins synthesis followed by memory disorders, was reflected in decrease of the synaptosomal proteins fraction which was identified as the cholinoreceptor protein. Another series of experiments: training of rats to use unpreferred paw, showed the system acetylcholine-acetylcholinesterase to be directly connected with memory phenomena, and the synthesis of this enzyme to be induced by genetic apparatus. The third series of experiments showed that feeding of rats with small doses of aminoacids for a long time leads to regular shifts in distribution of both the aminoacids and the monoamines. The aminoacids increasing the brain activity were found to activate the production of cycle-adenyl acid. Those aminoacids which inhibit the brain activity, decrease the production of cyclic-AMP. Tranquilizers which decrease the level of monoamines and inhibit the brain activity, also decrease the production of cyclic-AMP. Antidepressants inhibiting MAO and increasing the level of monoamines in the brain, activate the production of cyclic-AMP. As the monoamines act via cyclic-AMP and the latter participates in suppression of DNA, the mechanism of involvement of the genetic apparatus in regulation of memory phenomena and learning, becomes more apparent."}
{"id": "PMID:6343", "title": "[Mechanisms of pial artery responses in hypo- and hypertension].", "content": "Simultaneous study of the pial arterial responses and quantitative changes of the systemic arterial pressure, as well as of the PO2, pH and PCO2 on the brain surface, showed no correlation between the values and time of changes of the above parameters in rabbits. The vascular responses are concluded not to be caused by the direct action of either the changes of the intravascular pressure, or of the mentioned metabolites on the arterial walls, but rather to be due to another, probably nervous, feedback mechanism.", "contents": "[Mechanisms of pial artery responses in hypo- and hypertension]. Simultaneous study of the pial arterial responses and quantitative changes of the systemic arterial pressure, as well as of the PO2, pH and PCO2 on the brain surface, showed no correlation between the values and time of changes of the above parameters in rabbits. The vascular responses are concluded not to be caused by the direct action of either the changes of the intravascular pressure, or of the mentioned metabolites on the arterial walls, but rather to be due to another, probably nervous, feedback mechanism."}
{"id": "PMID:6345", "title": "[The chronotropic effect of maximal stress on the heart and its regulation].", "content": "The reflex bradycardia occurring at the maximal isometric heart strain produced by clamping of aorta was shown to be less intense if the heart rate prior to the experiment had been low. Vagotomy prevented or decreased the bradycardia. The beta-adrenoreceptor blockade with inderal significantly reduced the bradycardia, whereas the alpha-adrenoreceptor blockade with tropaphen increased it. The important role of relationship between adrenergic and cholinergic regulation of the heart in development of the bradycardia was discussed.", "contents": "[The chronotropic effect of maximal stress on the heart and its regulation]. The reflex bradycardia occurring at the maximal isometric heart strain produced by clamping of aorta was shown to be less intense if the heart rate prior to the experiment had been low. Vagotomy prevented or decreased the bradycardia. The beta-adrenoreceptor blockade with inderal significantly reduced the bradycardia, whereas the alpha-adrenoreceptor blockade with tropaphen increased it. The important role of relationship between adrenergic and cholinergic regulation of the heart in development of the bradycardia was discussed."}
{"id": "PMID:6346", "title": "[The effect of atropine on acid formation in the stomach].", "content": "In dogs, the effect of atropine on gastric acid secretion induced by food, mechanical stimuli, and histamine involved a complete block of the acid secretion but left the gastric secretory effect of histamine unaffected. Atropine caused about a twofold increase in duration of histamine-evoked acid secretion and a rise of the intragastric acidity in all parts of the stomach.", "contents": "[The effect of atropine on acid formation in the stomach]. In dogs, the effect of atropine on gastric acid secretion induced by food, mechanical stimuli, and histamine involved a complete block of the acid secretion but left the gastric secretory effect of histamine unaffected. Atropine caused about a twofold increase in duration of histamine-evoked acid secretion and a rise of the intragastric acidity in all parts of the stomach."}
{"id": "PMID:6347", "title": "Influence of the properties of skin allografts on the \"graft survival promoting effect\" of antilymphocyte serum.", "content": "Changes in the properties of non-H-2 imcompatible skin allografts, resulting from treating the graft donors with whole-body irradiation, antilymphocyte serum, cyclophosphamide, hydrocortisone, amethopterin and azathioprine, affected differently their survival in the recipients pretreated with normal and antilymphocyte serum. While in NS--pretreated recipients the modified grafts showed the tendency for a prolonged survival, in ALS-pretreated recipients they survived for a shorter time than normal allografts. In ALS-pretreated recipients, also allografts from radiation chimaeras, whose blood-forming system was of the recipient's genotype, survived worse than normal allografts and grafts from the donor syngeneic radiation chimaeras. The findings indicate that a normal physiological state of the graft is necessary for the induction and working of the protective components of the allotrasplantation reaction involved in the graft survival promoting effect of ALS. The significance of passenger leucocytes and of the functional properties of the graft, especially of the reparation cellular and extracellular processes is discussed.", "contents": "Influence of the properties of skin allografts on the \"graft survival promoting effect\" of antilymphocyte serum. Changes in the properties of non-H-2 imcompatible skin allografts, resulting from treating the graft donors with whole-body irradiation, antilymphocyte serum, cyclophosphamide, hydrocortisone, amethopterin and azathioprine, affected differently their survival in the recipients pretreated with normal and antilymphocyte serum. While in NS--pretreated recipients the modified grafts showed the tendency for a prolonged survival, in ALS-pretreated recipients they survived for a shorter time than normal allografts. In ALS-pretreated recipients, also allografts from radiation chimaeras, whose blood-forming system was of the recipient's genotype, survived worse than normal allografts and grafts from the donor syngeneic radiation chimaeras. The findings indicate that a normal physiological state of the graft is necessary for the induction and working of the protective components of the allotrasplantation reaction involved in the graft survival promoting effect of ALS. The significance of passenger leucocytes and of the functional properties of the graft, especially of the reparation cellular and extracellular processes is discussed."}
{"id": "PMID:6359", "title": "The effect of cimetidine, a new histamine H2-receptor antagonist, on meal-stimulated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcer.", "content": "Meal-stimulated acid secretion, measured by in vivo intragastric titration, was progressively inhibited by increasing oral doses of cimetidine (25 to 400 mg). Four hundred milligrams suppressed acid secretion by 73% for the first 3 hr after the meal, whereas it inhibited acid secretion by 94% during the 30-min period of maximal inhibition. The dose of cimetidine required to suppress acid secretion by 50% during the 30-min period of maximal inhibition was 25 mg. The duration of action of a 300-mg dose was at least 7 hr. Cimetidine was equally effective in inhibiting meal-stimulated acid secretion at two physiological intragastric pH levels (5.0 and 2.5). Cimetidine had no effect on serum gastrin concentration when intragastric pH was maintained at 5.0, but when pH was allowed to seek its own level, serum gastrin concentration was higher after cimetidine than after placebo. Cimetidine had no effect on gastric emptying. No side effects were noted in any patients.", "contents": "The effect of cimetidine, a new histamine H2-receptor antagonist, on meal-stimulated acid secretion, serum gastrin, and gastric emptying in patients with duodenal ulcer. Meal-stimulated acid secretion, measured by in vivo intragastric titration, was progressively inhibited by increasing oral doses of cimetidine (25 to 400 mg). Four hundred milligrams suppressed acid secretion by 73% for the first 3 hr after the meal, whereas it inhibited acid secretion by 94% during the 30-min period of maximal inhibition. The dose of cimetidine required to suppress acid secretion by 50% during the 30-min period of maximal inhibition was 25 mg. The duration of action of a 300-mg dose was at least 7 hr. Cimetidine was equally effective in inhibiting meal-stimulated acid secretion at two physiological intragastric pH levels (5.0 and 2.5). Cimetidine had no effect on serum gastrin concentration when intragastric pH was maintained at 5.0, but when pH was allowed to seek its own level, serum gastrin concentration was higher after cimetidine than after placebo. Cimetidine had no effect on gastric emptying. No side effects were noted in any patients."}
{"id": "PMID:6360", "title": "Role of fat maldigestion in pathogenesis of steatorrhea in ileal resection. Fat digestion after two sequential test meals with and without cholestyramine.", "content": "To clarify the role of fat maldigestion in the pathogenesis of steatorrhea in patients with ileal resection the total and aqueous phase concentrations of bile acid and fatty acid were characterized in 8 such patients (5 patients with small ileal resection, bile acid diarrhea, and steatorrhea less than 20 g per day; 3 patients with large ileal resection, fatty acid diarrhea, and steatorrhea greater than 20 g per day) as well as 4 healthy control subjects after a morning and an afternoon liquid test meal. The study was then repeated with cholestyramine, 4 g being administered before each meal to induce fat maldigestion. After a conventional test meal, patients with large resections and severe steatorrhea had significantly lower aqueous phase concentrations of bile acids (and fatty acids) than patients with smaller resections or control subjects, explained in part by intraluminal precipitation of about one-half of the bile acids during digestion. When cholestyramine was administered before the meal, aqueous phase bile acid concentrations decreased in all patients, including the normal control subjects; the degree of fat maldigestion induced in the patients with small resections (and the control subjects) became similar to that present after the conventional test meal in the patients with large resections. Because steatorrhea increased little in the patients with small resections when cholestyramine was administered continuously, the data suggest that fat maldigestion per se does not induce severe fat malabsorption in patients with sufficient anatomical reserve, because such patients can absorb fat efficiently by utilizing the distal small intestine. In patients with large ileal resections, severe steatorrhea is explained in part by the combination of fat maldigestion and decreased surface area. It is also speculated that the steatorrhea occurring in patients with small resections and relatively normal fat digestion during two test meals may be explained by impaired fat digestion which occurs during the final meal of the day, which is often the largest meal.", "contents": "Role of fat maldigestion in pathogenesis of steatorrhea in ileal resection. Fat digestion after two sequential test meals with and without cholestyramine. To clarify the role of fat maldigestion in the pathogenesis of steatorrhea in patients with ileal resection the total and aqueous phase concentrations of bile acid and fatty acid were characterized in 8 such patients (5 patients with small ileal resection, bile acid diarrhea, and steatorrhea less than 20 g per day; 3 patients with large ileal resection, fatty acid diarrhea, and steatorrhea greater than 20 g per day) as well as 4 healthy control subjects after a morning and an afternoon liquid test meal. The study was then repeated with cholestyramine, 4 g being administered before each meal to induce fat maldigestion. After a conventional test meal, patients with large resections and severe steatorrhea had significantly lower aqueous phase concentrations of bile acids (and fatty acids) than patients with smaller resections or control subjects, explained in part by intraluminal precipitation of about one-half of the bile acids during digestion. When cholestyramine was administered before the meal, aqueous phase bile acid concentrations decreased in all patients, including the normal control subjects; the degree of fat maldigestion induced in the patients with small resections (and the control subjects) became similar to that present after the conventional test meal in the patients with large resections. Because steatorrhea increased little in the patients with small resections when cholestyramine was administered continuously, the data suggest that fat maldigestion per se does not induce severe fat malabsorption in patients with sufficient anatomical reserve, because such patients can absorb fat efficiently by utilizing the distal small intestine. In patients with large ileal resections, severe steatorrhea is explained in part by the combination of fat maldigestion and decreased surface area. It is also speculated that the steatorrhea occurring in patients with small resections and relatively normal fat digestion during two test meals may be explained by impaired fat digestion which occurs during the final meal of the day, which is often the largest meal."}
{"id": "PMID:6361", "title": "Evaluation of esophageal tests in the diagnosis of reflux esophagitis.", "content": "The sensitivity and specificity of each of five esophageal tests used in the diagnosis of reflux esophagitis were compared with those of six combinations of two tests, one indicating esophagitis and the other indicating sphincter incompetence. The esophageal tests were performed in patients with reflux symptoms, chest pain, and esophagitis without reflux symptoms. Control data were obtained from normal subjects (negative control) and duodenal ulcer patients (positive control). The results indicate that the acid infusion test and esophageal biopsy combined with esophageal pH study after HC1 have similar sensitivity and greater specificity than any test alone. In normal subjects, the cumulative incidence of abnormalities with esophageal tests alone was 30%, but with combinations of two tests it was only 5%. The use of criteria (simultaneous esophagitis and sphincter incompetence) which establish the diagnosis of reflux esophagitis helps to resolve conflicting results obtained with single tests. The most sensitive and specific test combination for the diagnosis of reflux esophagitis appears to be esophageal biopsy with esophageal pH study after HC1.", "contents": "Evaluation of esophageal tests in the diagnosis of reflux esophagitis. The sensitivity and specificity of each of five esophageal tests used in the diagnosis of reflux esophagitis were compared with those of six combinations of two tests, one indicating esophagitis and the other indicating sphincter incompetence. The esophageal tests were performed in patients with reflux symptoms, chest pain, and esophagitis without reflux symptoms. Control data were obtained from normal subjects (negative control) and duodenal ulcer patients (positive control). The results indicate that the acid infusion test and esophageal biopsy combined with esophageal pH study after HC1 have similar sensitivity and greater specificity than any test alone. In normal subjects, the cumulative incidence of abnormalities with esophageal tests alone was 30%, but with combinations of two tests it was only 5%. The use of criteria (simultaneous esophagitis and sphincter incompetence) which establish the diagnosis of reflux esophagitis helps to resolve conflicting results obtained with single tests. The most sensitive and specific test combination for the diagnosis of reflux esophagitis appears to be esophageal biopsy with esophageal pH study after HC1."}
{"id": "PMID:6362", "title": "[Investigations on the distribution, cause and prevention of early perinatal morbidity (author's transl)].", "content": "These investigations were designed to detect causes of early perinatal morbidity in order to develop methods to decrease the perinatal morbidity in our unit. From October 1972 to December 1974 the most important antenatal, intrapartum and postpartum data on 2210 deliveries were coded. In 98% of the cases continuous fetal monitoring was performed. To detect early perinatal morbidity the acid base balance of all deliveries was measured from the umbilical vessels and the Apgar rating was determined at 1,5 and 10 minutes. The data show that a further decrease of the incidence of acidosis and low apgar scores is only possible in a limited way. Of the 13% deliveries with pH values of/or less than 7.15 or Apgar scores of/or less than 6 at 1 minute, only 5% appeared to be avoidable in this retrospective study. The incidence of severe acidosis decreased from 2.3% in 1972 to 1.3% in 1974. A comparison of the years 1973 and 1974 showed an improvement. Apgar scores of 6 or less at one minute decreased from 16 to 10% and severe acidosis with pH values of less than 7.10 decreased from 2.7% to 1.8%. In vaginal operative deliveries, the incidence of severe acidosis was reduced from 8.5% to 1.1%.", "contents": "[Investigations on the distribution, cause and prevention of early perinatal morbidity (author's transl)]. These investigations were designed to detect causes of early perinatal morbidity in order to develop methods to decrease the perinatal morbidity in our unit. From October 1972 to December 1974 the most important antenatal, intrapartum and postpartum data on 2210 deliveries were coded. In 98% of the cases continuous fetal monitoring was performed. To detect early perinatal morbidity the acid base balance of all deliveries was measured from the umbilical vessels and the Apgar rating was determined at 1,5 and 10 minutes. The data show that a further decrease of the incidence of acidosis and low apgar scores is only possible in a limited way. Of the 13% deliveries with pH values of/or less than 7.15 or Apgar scores of/or less than 6 at 1 minute, only 5% appeared to be avoidable in this retrospective study. The incidence of severe acidosis decreased from 2.3% in 1972 to 1.3% in 1974. A comparison of the years 1973 and 1974 showed an improvement. Apgar scores of 6 or less at one minute decreased from 16 to 10% and severe acidosis with pH values of less than 7.10 decreased from 2.7% to 1.8%. In vaginal operative deliveries, the incidence of severe acidosis was reduced from 8.5% to 1.1%."}
{"id": "PMID:6372", "title": "Sugar and amino acid transport in animal cells.", "content": "The molecular basis of intracellular metabolism of nutrients and its control is quite well understood in animal cells. Comparable knowledge about solute entry into cells is still lacking, as, in contrast to metabolism, no chemical reactions seem to be directly associated with the known nutrient transport. Nevertheless, translocations of sugars and amino acids across the plasma membrane are specific and controlled processes, biologically as well as chemically. Recent advances in techniques for isolation of plasma membranes have made it feasible to study transport properties of animal cells without the complications encoutered in viable cells. This approach has been applied to sugar and amino acid transport in plasma membranes of several tissues, and intact transport systems for D-glucose, D-fructose, neutral L-amino acids, and dipeptides have been demonstrated. This demonstration of intact transport systems in an in vitro setting accomplishes the first step in the direction of molecular isolation of transport systems. Furthermore, the information obtained about the transport mechanism catalyzed by some systems has settled controversies on active nutrient transport. For example, electrogenic cotransport of sodium and D-glucose or of sodium and neutral L-amino acids has been shown to form the basis for active, sodium-dependent absorption of these nutrients. A consequence of this type of mechanism is interaction between sugar and amino acid transport via the common charged cosubstrate sodium. Moreover, different types of transport systems for the same substrate have been demonstrated in the luminal and contraluminal regions of the plasma membrane of epithelial cells, which explains unidirectional transepithelial transport. The luminal membrane contains sodium-dependent, active transport systems, and the contraluminal membrane passive, facilitated diffusion systems. In vivo, the lower intracellular sodium potential would result in concentrative nutrient uptake from the lumen, but would not influence exit on the contraluminal side. Variations in the electrical components of the sodium potential, which have not been measured, may explain apparently contradicting results on active sugar and amino acid transport with various tissue preparations.", "contents": "Sugar and amino acid transport in animal cells. The molecular basis of intracellular metabolism of nutrients and its control is quite well understood in animal cells. Comparable knowledge about solute entry into cells is still lacking, as, in contrast to metabolism, no chemical reactions seem to be directly associated with the known nutrient transport. Nevertheless, translocations of sugars and amino acids across the plasma membrane are specific and controlled processes, biologically as well as chemically. Recent advances in techniques for isolation of plasma membranes have made it feasible to study transport properties of animal cells without the complications encoutered in viable cells. This approach has been applied to sugar and amino acid transport in plasma membranes of several tissues, and intact transport systems for D-glucose, D-fructose, neutral L-amino acids, and dipeptides have been demonstrated. This demonstration of intact transport systems in an in vitro setting accomplishes the first step in the direction of molecular isolation of transport systems. Furthermore, the information obtained about the transport mechanism catalyzed by some systems has settled controversies on active nutrient transport. For example, electrogenic cotransport of sodium and D-glucose or of sodium and neutral L-amino acids has been shown to form the basis for active, sodium-dependent absorption of these nutrients. A consequence of this type of mechanism is interaction between sugar and amino acid transport via the common charged cosubstrate sodium. Moreover, different types of transport systems for the same substrate have been demonstrated in the luminal and contraluminal regions of the plasma membrane of epithelial cells, which explains unidirectional transepithelial transport. The luminal membrane contains sodium-dependent, active transport systems, and the contraluminal membrane passive, facilitated diffusion systems. In vivo, the lower intracellular sodium potential would result in concentrative nutrient uptake from the lumen, but would not influence exit on the contraluminal side. Variations in the electrical components of the sodium potential, which have not been measured, may explain apparently contradicting results on active sugar and amino acid transport with various tissue preparations."}
{"id": "PMID:6391", "title": "Diethylaminoethyl-cellulose-bacterial cell immunoadsorbent columns: preparation of serotype-specific globulin and immunofluorescent conjugates for Streptococcus mutans serotypes a and d.", "content": "Diethylaminoethyl (DEAE)-cellulose was used as a support material for preparing bacterial cell columns. Pretreatment of the bacterial cells with formalin was essential in obtaining satisfactory adherence of the cells to DEAE-cellulose. Cross-reacting antibodies were removed from antibody preparations against strains of Streptococcus mutans serotypes a and d by adsorption on appropriate bacterial cell columns. S. mutans serotype d was further divided into two subtypes on the basis of immunofluorescent staining with conjugates of immunospecifically adsorbed immunoglobulin G. The DEAE-cellulose-bacterial cell columns were regenerated after use by desorbing the cross-reacting antibodies with low-pH buffer and were used repeatedly over and 18-month period with no detectable loss in effectiveness.", "contents": "Diethylaminoethyl-cellulose-bacterial cell immunoadsorbent columns: preparation of serotype-specific globulin and immunofluorescent conjugates for Streptococcus mutans serotypes a and d. Diethylaminoethyl (DEAE)-cellulose was used as a support material for preparing bacterial cell columns. Pretreatment of the bacterial cells with formalin was essential in obtaining satisfactory adherence of the cells to DEAE-cellulose. Cross-reacting antibodies were removed from antibody preparations against strains of Streptococcus mutans serotypes a and d by adsorption on appropriate bacterial cell columns. S. mutans serotype d was further divided into two subtypes on the basis of immunofluorescent staining with conjugates of immunospecifically adsorbed immunoglobulin G. The DEAE-cellulose-bacterial cell columns were regenerated after use by desorbing the cross-reacting antibodies with low-pH buffer and were used repeatedly over and 18-month period with no detectable loss in effectiveness."}
{"id": "PMID:6394", "title": "Kinetic studies of the alkaline mesentericopeptidase. Study on the active centre topography of alkaline mesentericopeptidase by means of bifunctional reversible inhibition.", "content": "The inhibitory effect of alkylboronic acids H(CH2)nB(OH)2(n=2-8) and Ph(CH2)n-B(OH)2, (n=0-4), on the alkaline mesentericopeptidase-catalysed hydrolysis of synthetic substrates was studied. It was shown that alkylboronic acids act as bifunctional reversible inhibitors. The borate group interacts with an ionogenic group of the enzyme with a pKa of about 6.9-7.0. The latter is probably the catalytically active imidazole of the active centre. The hydrocarbon part of the molecule also takes part in the formation of the enzyme-inhibitor complex. The dependence of the degree of the enzyme-inhibitor complex formation upon the length of the side-chain of the inhibitor indicates the presence of two binding sites on the enzyme molecule.", "contents": "Kinetic studies of the alkaline mesentericopeptidase. Study on the active centre topography of alkaline mesentericopeptidase by means of bifunctional reversible inhibition. The inhibitory effect of alkylboronic acids H(CH2)nB(OH)2(n=2-8) and Ph(CH2)n-B(OH)2, (n=0-4), on the alkaline mesentericopeptidase-catalysed hydrolysis of synthetic substrates was studied. It was shown that alkylboronic acids act as bifunctional reversible inhibitors. The borate group interacts with an ionogenic group of the enzyme with a pKa of about 6.9-7.0. The latter is probably the catalytically active imidazole of the active centre. The hydrocarbon part of the molecule also takes part in the formation of the enzyme-inhibitor complex. The dependence of the degree of the enzyme-inhibitor complex formation upon the length of the side-chain of the inhibitor indicates the presence of two binding sites on the enzyme molecule."}
{"id": "PMID:6395", "title": "Unusual behaviour of a protein: reversible quantitative precipitation of staphylococcal delta-haemolysin by low concentrations of some organic solvents.", "content": "Staphylococcal delta-haemolysin is precipitated from watery solutions by low concentrations of chloroform. The effect on this precipitation of pH, kind and concentration of salts, and concentration of, and time of exposure to, chloroform have been investigated. Some but not all of the other solvents tested cause a similar precipitation. The haemolytic activity is not destroyed and under appropriate conditions precipitation is quantitative. The dry lysin will take up nearly double its weight of chloroform when exposed to the vapour. Some is bound strongly.", "contents": "Unusual behaviour of a protein: reversible quantitative precipitation of staphylococcal delta-haemolysin by low concentrations of some organic solvents. Staphylococcal delta-haemolysin is precipitated from watery solutions by low concentrations of chloroform. The effect on this precipitation of pH, kind and concentration of salts, and concentration of, and time of exposure to, chloroform have been investigated. Some but not all of the other solvents tested cause a similar precipitation. The haemolytic activity is not destroyed and under appropriate conditions precipitation is quantitative. The dry lysin will take up nearly double its weight of chloroform when exposed to the vapour. Some is bound strongly."}
{"id": "PMID:6396", "title": "Deamidated active intermediates in the irreversible acid denaturation of ribonuclease-A.", "content": "A study has been made on the changes in the enzymatic activity of Ribonuclease-A**-(RNase-A) exposed to highly acidic (pH less than 1) acqueous environment. Irreversible alterations of activity were observed when the protein was exposed to an acidic medium for a long period (20 to 60 h). Even prior to these changes in activity RNase-A was found to form intermediates which had very nearly the same activity as the native protein. The primary process in the acid denaturation of RNase-A was observed to be deamidation of the protein leading to the formation of active chromotographically distinct derivatives. The initial product of deamidation, a monodeamidated derivative, has been isolated by chromatography on Amberlite XE-64. This initial deamidation reaction proceeded with very high specificity. The subsequent deamidation reaction is comparatively slower, so that nearly 50% of the native protein could be converted to this derivative before any subsequent deamidation took place. This monodeamidated derivative has been designated RNase-Aa1. The conversion of RNase-A to RNase-Aa1 was not accompanied by any changes in the primary structure other than the observed deamidation. Apart from the differences in chromatographic and electrophoretic mobilities, RNase-Aa1 was found to have very nearly the same activity and physicochemical properties as the native enzyme. Significance of this specific and faster deamidation of RNase-A in this denaturing medium as well as the biological significance of such deamidation reactions of proteins are discussed.", "contents": "Deamidated active intermediates in the irreversible acid denaturation of ribonuclease-A. A study has been made on the changes in the enzymatic activity of Ribonuclease-A**-(RNase-A) exposed to highly acidic (pH less than 1) acqueous environment. Irreversible alterations of activity were observed when the protein was exposed to an acidic medium for a long period (20 to 60 h). Even prior to these changes in activity RNase-A was found to form intermediates which had very nearly the same activity as the native protein. The primary process in the acid denaturation of RNase-A was observed to be deamidation of the protein leading to the formation of active chromotographically distinct derivatives. The initial product of deamidation, a monodeamidated derivative, has been isolated by chromatography on Amberlite XE-64. This initial deamidation reaction proceeded with very high specificity. The subsequent deamidation reaction is comparatively slower, so that nearly 50% of the native protein could be converted to this derivative before any subsequent deamidation took place. This monodeamidated derivative has been designated RNase-Aa1. The conversion of RNase-A to RNase-Aa1 was not accompanied by any changes in the primary structure other than the observed deamidation. Apart from the differences in chromatographic and electrophoretic mobilities, RNase-Aa1 was found to have very nearly the same activity and physicochemical properties as the native enzyme. Significance of this specific and faster deamidation of RNase-A in this denaturing medium as well as the biological significance of such deamidation reactions of proteins are discussed."}
{"id": "PMID:6397", "title": "Covalent coupling of bilirubin to albumin.", "content": "A method for covalent coupling of bilirubin to albumin is described. Human serum albumin-bilirubin (1:1 complex) has been treated with water soluble carbodiimide in order to obtain covalent coupling of bilirubin to albumin. The reaction conditions have been varied with respect to pH, reaction time and concentration of reagent to obtain the optimal coupling. The prepared albumin-bilirubin compounds were investigated by spectrophotometry, gel filtration and gel electrophoresis to ascertain the covalent nature of the bond and to characterize the products further. Gel electrophoresis and gel filtration showed that a monomer fraction could be prepared, and this fraction was a suitable material for further studies.", "contents": "Covalent coupling of bilirubin to albumin. A method for covalent coupling of bilirubin to albumin is described. Human serum albumin-bilirubin (1:1 complex) has been treated with water soluble carbodiimide in order to obtain covalent coupling of bilirubin to albumin. The reaction conditions have been varied with respect to pH, reaction time and concentration of reagent to obtain the optimal coupling. The prepared albumin-bilirubin compounds were investigated by spectrophotometry, gel filtration and gel electrophoresis to ascertain the covalent nature of the bond and to characterize the products further. Gel electrophoresis and gel filtration showed that a monomer fraction could be prepared, and this fraction was a suitable material for further studies."}
{"id": "PMID:6398", "title": "Inactivation of trypsin and chymotrypsin with a photosensitive probe.", "content": "The photosensitive inactivation of trypsin and chymotrypsin by 4-fluoro-3-nitrophenyl azide (FNPA) is described. A dark inhibition was observed at elevated probe concentrations, and was reversible. The enzymes were stable to photolysis in the absence of probe. Photolytic inactivation of trypsin and chymotrypsin with FNPA was found to be irreversible, and occurs in minutes at concentrations of FNPA where dark inhibition is negligible. The photoprobe was equally effective at pH 3 or pH 8. Nonspecific inactivation appears to be low, as evidenced by the stability of glucose oxidase and peroxidase to photolysis with FNPA.", "contents": "Inactivation of trypsin and chymotrypsin with a photosensitive probe. The photosensitive inactivation of trypsin and chymotrypsin by 4-fluoro-3-nitrophenyl azide (FNPA) is described. A dark inhibition was observed at elevated probe concentrations, and was reversible. The enzymes were stable to photolysis in the absence of probe. Photolytic inactivation of trypsin and chymotrypsin with FNPA was found to be irreversible, and occurs in minutes at concentrations of FNPA where dark inhibition is negligible. The photoprobe was equally effective at pH 3 or pH 8. Nonspecific inactivation appears to be low, as evidenced by the stability of glucose oxidase and peroxidase to photolysis with FNPA."}
{"id": "PMID:6401", "title": "Pathways of the eye's response to topical nitrogen mustard.", "content": "We studied the effect of prior corneal herpes simplex infection with its resultant corneal hypesthesia on the irritative response of the rabbit eye to topical nitrogen mustard. Both the miosis and the breakdown of the blood-aqueous barrier that follow the application of topical nitrogen mustard were diminished in eyes infected three weeks previously with herpes simplex virus. Nonspecific corneal scarring did not affect the response. This suggests again that an axon reflex requiring intact sensory innervation mediates the response to nitrogen mustard. Pretreatment of normal (noninfected) rabbits with systemic H1 and H2 antihistamines, topical scopolamine hydrobromide, or topical and systemic corticosteroids was ineffective in blocking the miosis or increased protein in the aqueous humor following topical nitrogen mustard.", "contents": "Pathways of the eye's response to topical nitrogen mustard. We studied the effect of prior corneal herpes simplex infection with its resultant corneal hypesthesia on the irritative response of the rabbit eye to topical nitrogen mustard. Both the miosis and the breakdown of the blood-aqueous barrier that follow the application of topical nitrogen mustard were diminished in eyes infected three weeks previously with herpes simplex virus. Nonspecific corneal scarring did not affect the response. This suggests again that an axon reflex requiring intact sensory innervation mediates the response to nitrogen mustard. Pretreatment of normal (noninfected) rabbits with systemic H1 and H2 antihistamines, topical scopolamine hydrobromide, or topical and systemic corticosteroids was ineffective in blocking the miosis or increased protein in the aqueous humor following topical nitrogen mustard."}
{"id": "PMID:6402", "title": "Intraocular pressure decrease in normal volunteers following timolol ophthalmic solution.", "content": "Timolol ophthalmic solutions 0.5 per cent, 1.0 per cent, and 1.5 per cent lowered intraocular pressures significantly in normal human volunteers. Maximum lowering of the intraocular pressures was reached at two hours with the 0.5 per cent solution of timolol and at one hour with the 1.0 per cent and 1.5 per cent timolol ophthalmic solutions. The effect lasted the full seven hours of observations. No objective or subjective evidence of ocular irritation could be attributed to the drug. A single dose of timolol applied topically to the eyes of normal human volunteers had no effect on pupillary size, visual acuity, blood pressure, or pulse rate.", "contents": "Intraocular pressure decrease in normal volunteers following timolol ophthalmic solution. Timolol ophthalmic solutions 0.5 per cent, 1.0 per cent, and 1.5 per cent lowered intraocular pressures significantly in normal human volunteers. Maximum lowering of the intraocular pressures was reached at two hours with the 0.5 per cent solution of timolol and at one hour with the 1.0 per cent and 1.5 per cent timolol ophthalmic solutions. The effect lasted the full seven hours of observations. No objective or subjective evidence of ocular irritation could be attributed to the drug. A single dose of timolol applied topically to the eyes of normal human volunteers had no effect on pupillary size, visual acuity, blood pressure, or pulse rate."}
{"id": "PMID:6403", "title": "The adrenergic receptors of the intraocular muscles of the human eye.", "content": "The adrenergic receptors in man were analyzed using isolated sphincter, dilator, and ciliary muscle strips, dissected from eyebank eyes. The dilator is mainly alpha, the sphincter both alpha and beta, and the ciliary muscle predominantly beta adrenergic.", "contents": "The adrenergic receptors of the intraocular muscles of the human eye. The adrenergic receptors in man were analyzed using isolated sphincter, dilator, and ciliary muscle strips, dissected from eyebank eyes. The dilator is mainly alpha, the sphincter both alpha and beta, and the ciliary muscle predominantly beta adrenergic."}
{"id": "PMID:6404", "title": "pH-dependent temperature sensitivity of rat lens phosphofructokinase.", "content": "Rat lens phosphofructokinase (PFK) has been found to be cold-labile at acidic pH, even in the presence of sulfate and inorganic phosphate, two known positive effectors. The inactivation appears to be an irreversible process, but can be prevented by including ATP in the incubating media. The enzyme is relatively stable at pH 8.2 incubated at 0 to 4 degrees, 25 degrees, or 37 degrees C. in the absence of the effectors, but is extremely thermolabile if the pH is lowered to 7.30 or lower. The thermolability is counteracted by many effectors, among them sulfate and ATP are the most effective. The physiologic significance of PFK instability and effector protection in the lens are discussed.", "contents": "pH-dependent temperature sensitivity of rat lens phosphofructokinase. Rat lens phosphofructokinase (PFK) has been found to be cold-labile at acidic pH, even in the presence of sulfate and inorganic phosphate, two known positive effectors. The inactivation appears to be an irreversible process, but can be prevented by including ATP in the incubating media. The enzyme is relatively stable at pH 8.2 incubated at 0 to 4 degrees, 25 degrees, or 37 degrees C. in the absence of the effectors, but is extremely thermolabile if the pH is lowered to 7.30 or lower. The thermolability is counteracted by many effectors, among them sulfate and ATP are the most effective. The physiologic significance of PFK instability and effector protection in the lens are discussed."}
{"id": "PMID:6405", "title": "The fetal renin-angiotensin system in normal and hypertensive pregnancy.", "content": "Plasma angiotensin II was measured in the umbilical cord arterial and/or venous blood of 54 babies delivered vaginally and in 12 delivered by elective lower segment cesarean section. Angiotensin II was also measured in the peripheral venous blood of 51 of the mothers. Mean angiotensin II levels at delivery were higher in the cord venous blood of infants born to hypertensive than to normotensive mothers. Cord venous angiotensin II levels were always higher than those of the mother and there was a strongly positive relationship between maternal and fetal angiotensin II. The duration of the second stage of labor was found significantly to affect fetal angiotensin II levels, prolonged labor being associated with high levels. When this was taken into account, there was a highly significant positive relationship between the body weight of the infants and cord venous angiotensin II levels. There was an inverse relationship between cord venous pH and angiotensin II levels. Babies delivered by lower segment cesarean section had much lower angiotensin II levels than those delivered vaginally. The levels were, however, twice as high as those in the nonpregnant adult.", "contents": "The fetal renin-angiotensin system in normal and hypertensive pregnancy. Plasma angiotensin II was measured in the umbilical cord arterial and/or venous blood of 54 babies delivered vaginally and in 12 delivered by elective lower segment cesarean section. Angiotensin II was also measured in the peripheral venous blood of 51 of the mothers. Mean angiotensin II levels at delivery were higher in the cord venous blood of infants born to hypertensive than to normotensive mothers. Cord venous angiotensin II levels were always higher than those of the mother and there was a strongly positive relationship between maternal and fetal angiotensin II. The duration of the second stage of labor was found significantly to affect fetal angiotensin II levels, prolonged labor being associated with high levels. When this was taken into account, there was a highly significant positive relationship between the body weight of the infants and cord venous angiotensin II levels. There was an inverse relationship between cord venous pH and angiotensin II levels. Babies delivered by lower segment cesarean section had much lower angiotensin II levels than those delivered vaginally. The levels were, however, twice as high as those in the nonpregnant adult."}
{"id": "PMID:6406", "title": "Use of salazopyrin for prevention of peritoneal adhesions in rats.", "content": "The effect of orally administered salazopyrin on the prevention of experimentally induced peritoneal adhesions in albino rats was investigated. Comparison of the findings with those for untreated rats and rats given penicillin for sulfadiazine indicated that salazopyrin has a preventive effect on the development of peritoneal adhesions. This effect is dose dependent and does not seem to be due merely to the antibacterial effect of the drug.", "contents": "Use of salazopyrin for prevention of peritoneal adhesions in rats. The effect of orally administered salazopyrin on the prevention of experimentally induced peritoneal adhesions in albino rats was investigated. Comparison of the findings with those for untreated rats and rats given penicillin for sulfadiazine indicated that salazopyrin has a preventive effect on the development of peritoneal adhesions. This effect is dose dependent and does not seem to be due merely to the antibacterial effect of the drug."}
{"id": "PMID:6407", "title": "[Optimal dosage in peroral therapy of acne with vitamin A palmitate].", "content": "Successful oral therapy with vitamin A palmitate in acne vulgaris requires 150,000-200,000 I.U. daily for months. Side-effects were evaluated in 22 patients and in addition in 54 patients receiving 400,000 and 300,000 I.U. respectively for 3-4 weeks (SGPT, GGPT, Quick, electrophoresis, creatinine, bromosulfthaleine excretion). The same tests were done in 32 patients, who had received vitamin A palmitate 150,000-200,000 I.U. daily for at least half a year. Clinical experience and the presented data allow the following conclusions: There is no risk of liver impairement when 150,000-200,000 I.U. are given daily over extended periods. Doses over 300,000 I.U. are accompanied with liver impairement. During long-term treatment y-GT test should be performed regularly. Contraceptive advices are recommended.", "contents": "[Optimal dosage in peroral therapy of acne with vitamin A palmitate]. Successful oral therapy with vitamin A palmitate in acne vulgaris requires 150,000-200,000 I.U. daily for months. Side-effects were evaluated in 22 patients and in addition in 54 patients receiving 400,000 and 300,000 I.U. respectively for 3-4 weeks (SGPT, GGPT, Quick, electrophoresis, creatinine, bromosulfthaleine excretion). The same tests were done in 32 patients, who had received vitamin A palmitate 150,000-200,000 I.U. daily for at least half a year. Clinical experience and the presented data allow the following conclusions: There is no risk of liver impairement when 150,000-200,000 I.U. are given daily over extended periods. Doses over 300,000 I.U. are accompanied with liver impairement. During long-term treatment y-GT test should be performed regularly. Contraceptive advices are recommended."}
{"id": "PMID:6410", "title": "Chemical modification of streptovaricin C I. 19-O-substituted damavaricin C.", "content": "Damavaricin C, a degradative derivative of streptovaricin C, has reduced antibiotic activity relative to streptovaricin C. It has, however, a new phenolic hydroxyl group at the C-19 position of the naphthoquinone ring on which various groups can be substituted through an ether linkage. A series of 19-O-substituted derivatives of damavaricin C has been synthesized. The preparation of these derivatives, their in vitro antibacterial activities, in vitro inhibition of E. coli RNA polymerase, and lethal activity on the membrane mutants of E. coli are reported. It is believed that the original biological activity of damavaricin C is retained and that introduction of the functional groups at the C-19 position has increased the membrane diffusibility of the molecule.", "contents": "Chemical modification of streptovaricin C I. 19-O-substituted damavaricin C. Damavaricin C, a degradative derivative of streptovaricin C, has reduced antibiotic activity relative to streptovaricin C. It has, however, a new phenolic hydroxyl group at the C-19 position of the naphthoquinone ring on which various groups can be substituted through an ether linkage. A series of 19-O-substituted derivatives of damavaricin C has been synthesized. The preparation of these derivatives, their in vitro antibacterial activities, in vitro inhibition of E. coli RNA polymerase, and lethal activity on the membrane mutants of E. coli are reported. It is believed that the original biological activity of damavaricin C is retained and that introduction of the functional groups at the C-19 position has increased the membrane diffusibility of the molecule."}
{"id": "PMID:6411", "title": "Comparative in vitro activity of cephalosporins.", "content": "The in vitro activity of cephalexin, cephaloridine, cephalothin, cephapirin, cefoxitin, cephamycin C, cepharadine and cefazolin was determined against 443 isolates of bacteria. At a concentration of 12.5 mug/ml, all of the cephalosporins inhibited more than 60% of the isolates of Klebsiella pneumoniae. At the same concentration, cephalexin, cephaloridine, cephalothin, cephapirin, cephamycin C and cefazolin inhibited more than 90% of isolates of proteus mirabilis. All of the cephalosporins except cephalothin and cephapirin inhibited over 60% of isolates of Escherichia coli at a concentration of 12.5 mug/ml. Cefoxitin was the most active cephalosporin against gram-negative bacilli. There was substantial differences in the activity of cephalosporins against gram-positive cocci. Cephaloridine was the most active cephalosporin against these organisms. There was considerable fluctuation in the proportion of isolates of gram-negative bacilli susceptible to these cephalosporins from year to year, but there was no evidence to suggest that the number of resistant isolates was increasing.", "contents": "Comparative in vitro activity of cephalosporins. The in vitro activity of cephalexin, cephaloridine, cephalothin, cephapirin, cefoxitin, cephamycin C, cepharadine and cefazolin was determined against 443 isolates of bacteria. At a concentration of 12.5 mug/ml, all of the cephalosporins inhibited more than 60% of the isolates of Klebsiella pneumoniae. At the same concentration, cephalexin, cephaloridine, cephalothin, cephapirin, cephamycin C and cefazolin inhibited more than 90% of isolates of proteus mirabilis. All of the cephalosporins except cephalothin and cephapirin inhibited over 60% of isolates of Escherichia coli at a concentration of 12.5 mug/ml. Cefoxitin was the most active cephalosporin against gram-negative bacilli. There was substantial differences in the activity of cephalosporins against gram-positive cocci. Cephaloridine was the most active cephalosporin against these organisms. There was considerable fluctuation in the proportion of isolates of gram-negative bacilli susceptible to these cephalosporins from year to year, but there was no evidence to suggest that the number of resistant isolates was increasing."}
{"id": "PMID:6417", "title": "Oxygen dissociation curve for chorioallantoic capillary blood of chicken embryo.", "content": "Oxygen dissociation curves for blood in the chorioallantoic capillary of chicken embryos were determined using a microphotometric apparatus made for measuring the reaction velocity of a red blood cell with oxygen and carbon monoxide. The modified Hill's equations expressing the dissociation curve during development were calculated by two methods. P50's at pH of 7.4 were found to be 60.0, 54.4, 46.2, 33.1, and 28.6 mmHg for 10, 12, 14, 16 and 18 days of incubation, respectively. Although the Bohr factor did not show a clear relation to age, the oxygen affinity and the oxygen capacity tended to increase with the lapse of days, and the power of heme-to-heme interaction, to decrease with age. The findings imply that there is a respiratory adaptation of embryos during development.", "contents": "Oxygen dissociation curve for chorioallantoic capillary blood of chicken embryo. Oxygen dissociation curves for blood in the chorioallantoic capillary of chicken embryos were determined using a microphotometric apparatus made for measuring the reaction velocity of a red blood cell with oxygen and carbon monoxide. The modified Hill's equations expressing the dissociation curve during development were calculated by two methods. P50's at pH of 7.4 were found to be 60.0, 54.4, 46.2, 33.1, and 28.6 mmHg for 10, 12, 14, 16 and 18 days of incubation, respectively. Although the Bohr factor did not show a clear relation to age, the oxygen affinity and the oxygen capacity tended to increase with the lapse of days, and the power of heme-to-heme interaction, to decrease with age. The findings imply that there is a respiratory adaptation of embryos during development."}
{"id": "PMID:6418", "title": "Failure of histamine antagonists to prevent hypoxic pulmonary vasoconstriction in dogs.", "content": "The role of histamine as a mediator of hypoxic pulmonary vasoconstriction was examined in intact anesthetized dogs. Antagonism of histamine vasoconstrictor (H1) receptors with a classic antihistaminic drug (chlorpheniramine) failed to prevent or modify the pulmonary vascular responses to hypoxia (10% O2). Blockade of histamine vasodilator (H2) receptors with a newly synthesized blocking agent (metiamide) potentiated the vasoconstriction induced by hypoxia and prevented the normal increase in heart rate. Combined H1- and H2-receptor blockade also did not prevent or reduce the hypoxic pulmonary pressor response, although it did effectively abolish the cardiovascular actions of infused histamine. In other dogs, histamine infused (3.6 mug/kg per min) during hypoxia attenuated the pulmonary vasoconstriction induced by hypoxia. The results imply that, in the dog, histamine does not mediate hypoxic pulmonary vasoconstriction. However, histamine does appear to be released during hypoxia, and it may play a role in modulating the pulmonary vascular responses to hypoxia by opposing the hypoxia induced vasoconstriction. The results also imply that histamine may be responsible for the increase in heart rate during hypoxia.", "contents": "Failure of histamine antagonists to prevent hypoxic pulmonary vasoconstriction in dogs. The role of histamine as a mediator of hypoxic pulmonary vasoconstriction was examined in intact anesthetized dogs. Antagonism of histamine vasoconstrictor (H1) receptors with a classic antihistaminic drug (chlorpheniramine) failed to prevent or modify the pulmonary vascular responses to hypoxia (10% O2). Blockade of histamine vasodilator (H2) receptors with a newly synthesized blocking agent (metiamide) potentiated the vasoconstriction induced by hypoxia and prevented the normal increase in heart rate. Combined H1- and H2-receptor blockade also did not prevent or reduce the hypoxic pulmonary pressor response, although it did effectively abolish the cardiovascular actions of infused histamine. In other dogs, histamine infused (3.6 mug/kg per min) during hypoxia attenuated the pulmonary vasoconstriction induced by hypoxia. The results imply that, in the dog, histamine does not mediate hypoxic pulmonary vasoconstriction. However, histamine does appear to be released during hypoxia, and it may play a role in modulating the pulmonary vascular responses to hypoxia by opposing the hypoxia induced vasoconstriction. The results also imply that histamine may be responsible for the increase in heart rate during hypoxia."}
{"id": "PMID:6419", "title": "Circulatory effects of prolonged hypoxia before and during antihistamine.", "content": "Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.", "contents": "Circulatory effects of prolonged hypoxia before and during antihistamine. Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent."}
{"id": "PMID:6420", "title": "Dual contribution theory of regulation of CSF HCO3 in respiratory acidosis.", "content": "Regulation of CSF HCO3-in respiratory acidosis was studied in light of the \"dual contribution theory,\" which proposed that there were two sources for the CSF HCO3-increase: 1) HCO3-by diffusion from plasma and 2) HCO3-generated in the CNS and catalyzed by the local carbonic anhydrase (J. Appl. Physiol. 38: 504-512, 1975). In anesthetized dogs with an increase in Paco2 of 30 mmHg for 4 h the plasma HCO3 increased 2 meq/1 and CSF 6 meq/1. In combined respiratory and metabolic acidosis, plasma HCO3-did not increase but CSF HCO3-increased 6 meq/1. In combined acidosis and intraventricular injections of acetazolamide no increase in plasma or CSF HCO3-occurred. In combined respiratory acidosis and metabolic alkalosis and intraventricular acetazolamide, plasma HCO3-increased 15 meq/1 but CSF HCO3-increased 6 meq/1. Brain and CSF ammonia increased linearly and selectively with the increase in the relative contribution of CNS HCO3-increase. Therefore regulation of CSF HCO3-in respiratory acidosis depends on both components of the dual contribution theory, where each component can provide the total CSF HCO3-increase under appropriate experimental conditions. The control mechanism may be sensitive to changes in [H+] on the brain side of the blood-brain barrier.", "contents": "Dual contribution theory of regulation of CSF HCO3 in respiratory acidosis. Regulation of CSF HCO3-in respiratory acidosis was studied in light of the \"dual contribution theory,\" which proposed that there were two sources for the CSF HCO3-increase: 1) HCO3-by diffusion from plasma and 2) HCO3-generated in the CNS and catalyzed by the local carbonic anhydrase (J. Appl. Physiol. 38: 504-512, 1975). In anesthetized dogs with an increase in Paco2 of 30 mmHg for 4 h the plasma HCO3 increased 2 meq/1 and CSF 6 meq/1. In combined respiratory and metabolic acidosis, plasma HCO3-did not increase but CSF HCO3-increased 6 meq/1. In combined acidosis and intraventricular injections of acetazolamide no increase in plasma or CSF HCO3-occurred. In combined respiratory acidosis and metabolic alkalosis and intraventricular acetazolamide, plasma HCO3-increased 15 meq/1 but CSF HCO3-increased 6 meq/1. Brain and CSF ammonia increased linearly and selectively with the increase in the relative contribution of CNS HCO3-increase. Therefore regulation of CSF HCO3-in respiratory acidosis depends on both components of the dual contribution theory, where each component can provide the total CSF HCO3-increase under appropriate experimental conditions. The control mechanism may be sensitive to changes in [H+] on the brain side of the blood-brain barrier."}
{"id": "PMID:6421", "title": "Effects of continuous positive-pressure ventilation in experimental pulmonary edema.", "content": "We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function.", "contents": "Effects of continuous positive-pressure ventilation in experimental pulmonary edema. We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function."}
{"id": "PMID:6422", "title": "Evaluation of a dual-function pH and PCO2 in vivo sensor.", "content": "A newly developed, dual-function pH and PCO2 sensor was evaluated in this study. The sensors were placed in the femoral arteries of dogs anesthetized with sodium pentobarbital. Comparisons were made between systemic arterial pH and PCO2 measured using the sensor and those measured from blood samples drawn at 15-min intervals over a 7-h period using a bench instrument. The mean pH of the bench instrument measurements was 7.43. The mean difference of the sensor measurements from the bench instrument measurements for 207 comparisons was 0.0003 pH +/- 0.061 SD. The mean PCO2 of the bench instrument measurements was 40 mmHg. The mean difference of the sensor measurements from those of the bench instrument for 212 comparisons was -1.43 mmHg +/- 5.17 SD. The sensors performed equally well in the presence of metabolic or respiratory acidosis and alkalosis. The dual-function sensors evaluated in this study are useful for trend monitoring of pH and PCO2 over at least a 7-h period without recalibration. With improvement in the consistency of sensor construction, these sensors will be reliable in vivo sensing devices for blood pH and PCO2 and thus valuable research and clinical instruments.", "contents": "Evaluation of a dual-function pH and PCO2 in vivo sensor. A newly developed, dual-function pH and PCO2 sensor was evaluated in this study. The sensors were placed in the femoral arteries of dogs anesthetized with sodium pentobarbital. Comparisons were made between systemic arterial pH and PCO2 measured using the sensor and those measured from blood samples drawn at 15-min intervals over a 7-h period using a bench instrument. The mean pH of the bench instrument measurements was 7.43. The mean difference of the sensor measurements from the bench instrument measurements for 207 comparisons was 0.0003 pH +/- 0.061 SD. The mean PCO2 of the bench instrument measurements was 40 mmHg. The mean difference of the sensor measurements from those of the bench instrument for 212 comparisons was -1.43 mmHg +/- 5.17 SD. The sensors performed equally well in the presence of metabolic or respiratory acidosis and alkalosis. The dual-function sensors evaluated in this study are useful for trend monitoring of pH and PCO2 over at least a 7-h period without recalibration. With improvement in the consistency of sensor construction, these sensors will be reliable in vivo sensing devices for blood pH and PCO2 and thus valuable research and clinical instruments."}
{"id": "PMID:6423", "title": "Polymer membrane sensors for continuous intravascular monitoring of blood pH.", "content": "A new type of pH sensor suitable for chronic intra-vascular implantation by virtue of its small size, flexibility, and ruggedness was constructed and evaluated. The pH-sensitive element was a thin film of an elastromeric polymer made ion permselective to proteons by adding a lipophilic, specific H+-ion carrier. This was coated onto small diameter silver wires to form sensors. In preliminary trials in anesthetized dogs, the sensors permitted continuous, accurate in vivo blood pH measurement with rapid response (less than 0.1 s).", "contents": "Polymer membrane sensors for continuous intravascular monitoring of blood pH. A new type of pH sensor suitable for chronic intra-vascular implantation by virtue of its small size, flexibility, and ruggedness was constructed and evaluated. The pH-sensitive element was a thin film of an elastromeric polymer made ion permselective to proteons by adding a lipophilic, specific H+-ion carrier. This was coated onto small diameter silver wires to form sensors. In preliminary trials in anesthetized dogs, the sensors permitted continuous, accurate in vivo blood pH measurement with rapid response (less than 0.1 s)."}
{"id": "PMID:6424", "title": "Temperature-induced changes in blood acid-base status: pH and PCO2 in a binary buffer.", "content": "Equations for proton equilibria of a single-phase binary buffer system have been applied to temperature-induced changes in pH and PCO2 of separated dog plasma at constant carbon dioxide content. Predicted behaviour, measured as deltapH/deltaT and deltalog PCO2 /deltaT, and pH and PCO2 as a function of temperature (range 8-45 degrees C), are in reasonable agreement with theory. Theory predicts and data confirm that deltapH/delta T and deltalog PCO2/deltaT functions of temperature; no single \"temperature correction factor\" is applicable. Comparison of whole blood with binary buffer equations also shows acceptable agreement between theory and experiment. Blood and separated plasma show similar responses in deltapH/deltaT and deltalog PCO2/delta T when compared over identical temperature intervals. For blood or plasma with initial pH (AT 37.5 DEGREES C) values in the range 7.53-7.45 deltapH/delta T (u/ degrees C) values are -0.0139 (37.5-27.5 degrees C) and -0.0192 (19-7 degrees C); comparable deltalog PCO2/deltaT values are 0.0195 (37.5-27.5 degrees C) and 0.0240 (19-7 degrees C). The charge state of protein components in this system remains nearly constant as temperature varies.", "contents": "Temperature-induced changes in blood acid-base status: pH and PCO2 in a binary buffer. Equations for proton equilibria of a single-phase binary buffer system have been applied to temperature-induced changes in pH and PCO2 of separated dog plasma at constant carbon dioxide content. Predicted behaviour, measured as deltapH/deltaT and deltalog PCO2 /deltaT, and pH and PCO2 as a function of temperature (range 8-45 degrees C), are in reasonable agreement with theory. Theory predicts and data confirm that deltapH/delta T and deltalog PCO2/deltaT functions of temperature; no single \"temperature correction factor\" is applicable. Comparison of whole blood with binary buffer equations also shows acceptable agreement between theory and experiment. Blood and separated plasma show similar responses in deltapH/deltaT and deltalog PCO2/delta T when compared over identical temperature intervals. For blood or plasma with initial pH (AT 37.5 DEGREES C) values in the range 7.53-7.45 deltapH/delta T (u/ degrees C) values are -0.0139 (37.5-27.5 degrees C) and -0.0192 (19-7 degrees C); comparable deltalog PCO2/deltaT values are 0.0195 (37.5-27.5 degrees C) and 0.0240 (19-7 degrees C). The charge state of protein components in this system remains nearly constant as temperature varies."}
{"id": "PMID:6425", "title": "Temperature-induced changes in blood acid-base status: Donnan rCl and red cell volume.", "content": "The Donnan ratio for chloride ion (rCl) was determined for human red cells in plasma utilizing 36Cl. The effect of altered PCO2 and pH on rCl was followed in two ways. CO2 partial pressure was varied (1-1.5% CO2 in O2; pH range 7.1-7.9) at 37.5 degrees C (isothermal); PCO2 and pH were also changed by altering temperature (range 5-45 degrees C) at constant CO2 content (temperature induced). At pH 7.4 and 37.5 degrees C, rCl was 0.631 +/- 0.0269 (SE, N = 5); isothermal drcl/dpH = -0.306 +/- 0.0234. When measured under conditions of variable temperature at constant CO2 content (pH range 7.3-7.9), drcl/dpH = .018 +/- 0.0232, significantly different from isothermal response (P less than 0.001). Hematocrit (H) changes with pH for conditions of initial H(7.4) of 0.45, under these conditions were also determined: isothermal dH/dpH = -0.031 +/- 0.0019; temperature induced, -0.004 +/- 0.0009. Temperature change alone at constant carbon dioxide content produces no significant change in distribution of chloride ions or water between erythrocyte and plasma compartments.", "contents": "Temperature-induced changes in blood acid-base status: Donnan rCl and red cell volume. The Donnan ratio for chloride ion (rCl) was determined for human red cells in plasma utilizing 36Cl. The effect of altered PCO2 and pH on rCl was followed in two ways. CO2 partial pressure was varied (1-1.5% CO2 in O2; pH range 7.1-7.9) at 37.5 degrees C (isothermal); PCO2 and pH were also changed by altering temperature (range 5-45 degrees C) at constant CO2 content (temperature induced). At pH 7.4 and 37.5 degrees C, rCl was 0.631 +/- 0.0269 (SE, N = 5); isothermal drcl/dpH = -0.306 +/- 0.0234. When measured under conditions of variable temperature at constant CO2 content (pH range 7.3-7.9), drcl/dpH = .018 +/- 0.0232, significantly different from isothermal response (P less than 0.001). Hematocrit (H) changes with pH for conditions of initial H(7.4) of 0.45, under these conditions were also determined: isothermal dH/dpH = -0.031 +/- 0.0019; temperature induced, -0.004 +/- 0.0009. Temperature change alone at constant carbon dioxide content produces no significant change in distribution of chloride ions or water between erythrocyte and plasma compartments."}
{"id": "PMID:6427", "title": "Influence of pH on the rate of ribosomal ribonucleic acid synthesis during sporulation in Saccharomyces cerevisiae.", "content": "The rate of synthesis of ribosomal RNA (rRNA) is much slower during sporulation than during vegetative growth of yeast. If sporulating cells are transferred from normal incubation conditions at pH 8.8 to the same medium adjusted to pH 7.0, the rate of rRNA synthesis increased to approach that observed in vegetative cells. The response to the pH change is quite rapid, occurring within 10 min. THE PH-dependent, rate-limiting step appears to be in the processing of 35S ribosomal precursor RNA to the final 26S and 18S RNA species. A similar pH effect also was found for the rate of protein synthesis. However, no change in respiration was observed when the pH was lowered. These results indicate that the observed differences in rate of rRNA synthesis in vegetative and sporulating cells are a consequence of pH and are not intrinsic to sporulation. The results also support the correlation between rRNA processing and protein synthesis.", "contents": "Influence of pH on the rate of ribosomal ribonucleic acid synthesis during sporulation in Saccharomyces cerevisiae. The rate of synthesis of ribosomal RNA (rRNA) is much slower during sporulation than during vegetative growth of yeast. If sporulating cells are transferred from normal incubation conditions at pH 8.8 to the same medium adjusted to pH 7.0, the rate of rRNA synthesis increased to approach that observed in vegetative cells. The response to the pH change is quite rapid, occurring within 10 min. THE PH-dependent, rate-limiting step appears to be in the processing of 35S ribosomal precursor RNA to the final 26S and 18S RNA species. A similar pH effect also was found for the rate of protein synthesis. However, no change in respiration was observed when the pH was lowered. These results indicate that the observed differences in rate of rRNA synthesis in vegetative and sporulating cells are a consequence of pH and are not intrinsic to sporulation. The results also support the correlation between rRNA processing and protein synthesis."}
{"id": "PMID:6426", "title": "Regulation of histidase synthesis in intergeneric hybrids of enteric bacteria.", "content": "Regulation of the expression of the histidase coded by hutk of Klebsiella aerogenes in Salmonella typhimurium and in Escherichia coli and of the expression of the histidase coded by huts of S. typhimurium in E. coli was investigated. The hutk histidase was found to be sensitive to catabolite repression in K. aerogenes and in E. coli, but insensitive to catabolite repression in S. typhimurium; huts histidase has previously been shown to be catabolite sensitive in all three organisms. The expression of both hutk and huts histidase in E. coli was activated by nitrogen starvation. Apparently, the glutamine synthetase of E. coli may activate the formation of some glutamate- and ammonia-producing enzymes.", "contents": "Regulation of histidase synthesis in intergeneric hybrids of enteric bacteria. Regulation of the expression of the histidase coded by hutk of Klebsiella aerogenes in Salmonella typhimurium and in Escherichia coli and of the expression of the histidase coded by huts of S. typhimurium in E. coli was investigated. The hutk histidase was found to be sensitive to catabolite repression in K. aerogenes and in E. coli, but insensitive to catabolite repression in S. typhimurium; huts histidase has previously been shown to be catabolite sensitive in all three organisms. The expression of both hutk and huts histidase in E. coli was activated by nitrogen starvation. Apparently, the glutamine synthetase of E. coli may activate the formation of some glutamate- and ammonia-producing enzymes."}
{"id": "PMID:6428", "title": "Role of polyadenylic acid in a deoxyribonucleic acid-membrane fraction extracted from pneumococci.", "content": "After the addition of radioactive polyadenylic acid to cell suspensions of pneumocci, part of the radioactivity becomes associated with a deoxyribonucleic acid (DNA)-membrane fraction extracted from the cells. A variety of techniques show that a portion of this associated radioactivity may represent oligoadenylates complexed to DNA, probaby as part of a ribonucleic acid (RNA) component. Polyadenylic acid, which had previously been shown to enhance DNA synthesis in cell suspensions (Firshein and Benson, 1968), also enhances the extent of DNA synthesis by the DNA-membrane fraction in vitro under specific conditions of concentration and conformation. The mechanism of action of this enhancement may be related to the ability of oligoadenylates to increase the number of initiation sites for DNA replication by stimulating the production of an RNA primer, thus providing additional 3'-OH groups with which DNA polymerase can react.", "contents": "Role of polyadenylic acid in a deoxyribonucleic acid-membrane fraction extracted from pneumococci. After the addition of radioactive polyadenylic acid to cell suspensions of pneumocci, part of the radioactivity becomes associated with a deoxyribonucleic acid (DNA)-membrane fraction extracted from the cells. A variety of techniques show that a portion of this associated radioactivity may represent oligoadenylates complexed to DNA, probaby as part of a ribonucleic acid (RNA) component. Polyadenylic acid, which had previously been shown to enhance DNA synthesis in cell suspensions (Firshein and Benson, 1968), also enhances the extent of DNA synthesis by the DNA-membrane fraction in vitro under specific conditions of concentration and conformation. The mechanism of action of this enhancement may be related to the ability of oligoadenylates to increase the number of initiation sites for DNA replication by stimulating the production of an RNA primer, thus providing additional 3'-OH groups with which DNA polymerase can react."}
{"id": "PMID:6429", "title": "Glutamate dehydrogenase: genetic mapping and isolation of regulatory mutants of Klebsiella aerogenes.", "content": "The gene for glutamate dehydrogenase (gdhD) has been mapped in Klebsiella aerogenes by P1 transduction. It is linked to pyrF and trp with the order pyrF-trp-gdh. Complementation analysis using F' episomes from Escherichia coli suggests an analogous location in E. coli. Two mutants able to produce glutamate dehydrogenase in the presence of high levels of glutamine synthetase have been isolated. One, tightly linked to gdhD, shows normal repression control by glutamine synthetase but produces four times as much glutamate dehydrogenase activity as does the wild type under all conditions tested. The other revertant is not linked to gdhD or glnA.", "contents": "Glutamate dehydrogenase: genetic mapping and isolation of regulatory mutants of Klebsiella aerogenes. The gene for glutamate dehydrogenase (gdhD) has been mapped in Klebsiella aerogenes by P1 transduction. It is linked to pyrF and trp with the order pyrF-trp-gdh. Complementation analysis using F' episomes from Escherichia coli suggests an analogous location in E. coli. Two mutants able to produce glutamate dehydrogenase in the presence of high levels of glutamine synthetase have been isolated. One, tightly linked to gdhD, shows normal repression control by glutamine synthetase but produces four times as much glutamate dehydrogenase activity as does the wild type under all conditions tested. The other revertant is not linked to gdhD or glnA."}
{"id": "PMID:6430", "title": "Adenosine 5'-triphosphate synthesis energized by an artificially imposed membrane potential in membrane vesicles of Escherichia coli.", "content": "Adenosine 5'-triphosphate (ATP) synthesis driven by an artificially imposed membrane potential in right-side-out membrane vesicles of Escherichia coli was investigated. Membrane vesicles prepared in the presence of adenosine diphosphate were loaded with K+ by incubation with 0.5 M potassium phosphate. Addition of valinomycin resulted in the synthesis of 0.2 to 0.3 nmol of ATP/mg of membrane protein, whereas no synthesis was observed after addition of nigericin. Addition of K+, dicyclohexylcarbodiimide, carbonylcyanide p-trifluoromethoxyphenylhydrazone, or azide to the assay buffer inhibited ATP synthesis. Adenosine diphosphate and Mg2+ were found to be required. Ca2+, which can replace Mg2+ for the hydrolytic activity of the Mg2+-adenosine triphosphatase (ATPase) (EC 3.6.1.3), could not replace Mg2+ in the synthetic reaction and, in fact, inhibited ATP synthesis even in the presence of Mg2+. Strain NR-70, a mutant lacking the Mg2+-ATPase, was unable to synthesize ATP using an artificially imposed membrane potential. Additionally, the Mg2+-ATPase was found to contain tightly bound ATP.", "contents": "Adenosine 5'-triphosphate synthesis energized by an artificially imposed membrane potential in membrane vesicles of Escherichia coli. Adenosine 5'-triphosphate (ATP) synthesis driven by an artificially imposed membrane potential in right-side-out membrane vesicles of Escherichia coli was investigated. Membrane vesicles prepared in the presence of adenosine diphosphate were loaded with K+ by incubation with 0.5 M potassium phosphate. Addition of valinomycin resulted in the synthesis of 0.2 to 0.3 nmol of ATP/mg of membrane protein, whereas no synthesis was observed after addition of nigericin. Addition of K+, dicyclohexylcarbodiimide, carbonylcyanide p-trifluoromethoxyphenylhydrazone, or azide to the assay buffer inhibited ATP synthesis. Adenosine diphosphate and Mg2+ were found to be required. Ca2+, which can replace Mg2+ for the hydrolytic activity of the Mg2+-adenosine triphosphatase (ATPase) (EC 3.6.1.3), could not replace Mg2+ in the synthetic reaction and, in fact, inhibited ATP synthesis even in the presence of Mg2+. Strain NR-70, a mutant lacking the Mg2+-ATPase, was unable to synthesize ATP using an artificially imposed membrane potential. Additionally, the Mg2+-ATPase was found to contain tightly bound ATP."}
{"id": "PMID:6431", "title": "Regulation of enzyme formation in Klebsiella aerogenes by episomal glutamine synthetase of Escherichia coli.", "content": "We studied the physiology of cells of Klebsiella aerogenes containing the structural gene for glutamine synthetase (glnA) of Escherichia coli on an episome. The E. coli glutamine synthetase functioned in cells of K. aerogenes in a manner similar to that of the K. aerogenes enzyme: it allowed the level of histidase to increase and that of glutamate dehydrogenase to decrease during nitrogen-limited growth. The phenotype of mutations in the glnA site was restored to normal by the introduction of the episomal glnA+ gene. These results are consistent with the hypothesis that glutamine synthetase regulates the function of its own structural gene.", "contents": "Regulation of enzyme formation in Klebsiella aerogenes by episomal glutamine synthetase of Escherichia coli. We studied the physiology of cells of Klebsiella aerogenes containing the structural gene for glutamine synthetase (glnA) of Escherichia coli on an episome. The E. coli glutamine synthetase functioned in cells of K. aerogenes in a manner similar to that of the K. aerogenes enzyme: it allowed the level of histidase to increase and that of glutamate dehydrogenase to decrease during nitrogen-limited growth. The phenotype of mutations in the glnA site was restored to normal by the introduction of the episomal glnA+ gene. These results are consistent with the hypothesis that glutamine synthetase regulates the function of its own structural gene."}
{"id": "PMID:6432", "title": "Kinetic properties of Serratia marcescens adenosine 5'-diphosphate glucose pyrophosphorylase.", "content": "The regulatory properties of partially purified adenosine 5'-diphosphate-(ADP) glucose pyrophosphorylase from two Serratia marcescens strains (ATCC 274 and ATCC 15365) have been studied. Slight or negligible activation by fructose-P2, pyridoxal-phosphate, or reduced nicotinamide adenine dinucleotide phosphate (NADPH) was observed. These compounds were previously shown to be potent activators of the ADPglucose pyrophosphorylases from the enterics, Salmonella typhimurium, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Escherichia aurescens, Shigella dysenteriae, and Escherichia coli. Phosphoenolpyruvate stimulated the rate of ADPglucose synthesis catalyzed by Serratia ADPglucose pyrophosphorylase about 1.5- to 2-fold but did not affect the S0.5 values (concentration of substrate required for 50% maximal stimulation) of the substrates, alpha-glucose-1-phosphate, and adenosine 5'-triphosphate. Adenosine 5'-monophosphate (AMP), a potent inhibitor of the enteric ADPglucose pyrophosphorylase, is an effective inhibitor of the S. marcescens enzyme. ADP also inhibits but is not as effective as AMP. Activators of the enteric enzyme counteract the inhibition caused by AMP. This is in contrast to what is observed for the S. marcescens enzyme. Neither phosphoenolpyruvate, fructose-diphosphate, pyridoxal-phosphate, NADPH, 3-phosphoglycerate, fructose-6-phosphate, nor pyruvate effect the inhibition caused by AMP. The properties of the S. marcescens HY strain and Serratia liquefaciens ADPglucose pyrophosphorylase were found to be similar to the above two S. marcescens enzymes with respect to activation and inhibition. These observations provide another example where the properties of an enzyme found in the genus Serratia have been found to be different from the properties of the same enzyme present in the enteric genera Escherichia, Salmonella, Shigella, Citrobacter, and Enterobacter.", "contents": "Kinetic properties of Serratia marcescens adenosine 5'-diphosphate glucose pyrophosphorylase. The regulatory properties of partially purified adenosine 5'-diphosphate-(ADP) glucose pyrophosphorylase from two Serratia marcescens strains (ATCC 274 and ATCC 15365) have been studied. Slight or negligible activation by fructose-P2, pyridoxal-phosphate, or reduced nicotinamide adenine dinucleotide phosphate (NADPH) was observed. These compounds were previously shown to be potent activators of the ADPglucose pyrophosphorylases from the enterics, Salmonella typhimurium, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Escherichia aurescens, Shigella dysenteriae, and Escherichia coli. Phosphoenolpyruvate stimulated the rate of ADPglucose synthesis catalyzed by Serratia ADPglucose pyrophosphorylase about 1.5- to 2-fold but did not affect the S0.5 values (concentration of substrate required for 50% maximal stimulation) of the substrates, alpha-glucose-1-phosphate, and adenosine 5'-triphosphate. Adenosine 5'-monophosphate (AMP), a potent inhibitor of the enteric ADPglucose pyrophosphorylase, is an effective inhibitor of the S. marcescens enzyme. ADP also inhibits but is not as effective as AMP. Activators of the enteric enzyme counteract the inhibition caused by AMP. This is in contrast to what is observed for the S. marcescens enzyme. Neither phosphoenolpyruvate, fructose-diphosphate, pyridoxal-phosphate, NADPH, 3-phosphoglycerate, fructose-6-phosphate, nor pyruvate effect the inhibition caused by AMP. The properties of the S. marcescens HY strain and Serratia liquefaciens ADPglucose pyrophosphorylase were found to be similar to the above two S. marcescens enzymes with respect to activation and inhibition. These observations provide another example where the properties of an enzyme found in the genus Serratia have been found to be different from the properties of the same enzyme present in the enteric genera Escherichia, Salmonella, Shigella, Citrobacter, and Enterobacter."}
{"id": "PMID:6433", "title": "Characterization of group B colicin-resistant mutants of Escherichia coli K-12: colicin resistance and the role of enterochelin.", "content": "Nine classes of group B colicin-resistant mutants were examined to study the role of enterochelin in colicin resistance. Four of the mutants studied (cbt, exbC, exbB, and tonB) hypersecreted enterochelin. Enterochelin hypersecretion was apparently responsible for resistance of the exbC mutant to colicins G and H and for resistance of the exbB mutant to colicins G, H, Ia, Ib, S1, and V. All four mutants scored as colicin B tolerant, even in the absence of enterochelin synthesis. The mutants produced substantially increased amounts of two high-molecular-weight outer membrane polypeptides when grown under limiting iron conditions. The presence of these polypeptides was correlated with increased colicin B-neutralizing activity in the outer membrane preparations.", "contents": "Characterization of group B colicin-resistant mutants of Escherichia coli K-12: colicin resistance and the role of enterochelin. Nine classes of group B colicin-resistant mutants were examined to study the role of enterochelin in colicin resistance. Four of the mutants studied (cbt, exbC, exbB, and tonB) hypersecreted enterochelin. Enterochelin hypersecretion was apparently responsible for resistance of the exbC mutant to colicins G and H and for resistance of the exbB mutant to colicins G, H, Ia, Ib, S1, and V. All four mutants scored as colicin B tolerant, even in the absence of enterochelin synthesis. The mutants produced substantially increased amounts of two high-molecular-weight outer membrane polypeptides when grown under limiting iron conditions. The presence of these polypeptides was correlated with increased colicin B-neutralizing activity in the outer membrane preparations."}
{"id": "PMID:6434", "title": "Metabolism of the reserve polysaccharide of Streptococcus mitior (mitis): is there a second alpha-1,4-glucan phosphorylase?", "content": "The alpha-1,4-glucan phosphorylase (alpha-1,4-glucan: orthophosphate glucosyltransferase; EC 2.4.1.1) associated with the particulate cell fraction of Streptococcus mitior strain S3 was compared with the soluble maltodextrin phosphorylase that had been previously isolated from the same organism (Walker et al., 1969). The particulate enzyme was more sensitive to the glycogen content of the cell than the soluble euzyme; its activity was highest when the cells were grown under conditions favoring high glycogen storage. Substrate specificities of the two high activity towards endogenous glycogen, whereas low-molecular-weight maltodextrins were the preferred substrates for the soluble phosphorylase. The purification of the particulate phosphorylase included incubation of the particulate fraction in 160 mM sodium phosphate-10 mM sodium citrate-0.1% (wt/vol) Triton X-100 buffer (pH 6.7) and ion-exchange chromatography on diethylamino-ethyl- Sephadex A-50. The purified enzyme was fully soluble. The value for the purification factor was variable and depended on (i) the substrate used and (ii) whether the synthetic or the degradative reaction was being measured. The solubilization resulted in considerable changes in the properties of the phosphorylase: the pH optimum for activity was raised from 6.0 to 7.0-7.5 and the substrate specificity was altered. Consequently, the purified enzyme bore greater similarity to the soluble maltodextrin phosphorylase. The reported results are best explained in terms of a single phosphorylase, the specificity which is determind by its binding state in the cell. The enzyme acts as a glycogen phosphorylase in the particulate state and as a maltodextrin phosphorylase when soluble. The equilibrium between the two forms is related to the glycogen content of the cells.", "contents": "Metabolism of the reserve polysaccharide of Streptococcus mitior (mitis): is there a second alpha-1,4-glucan phosphorylase? The alpha-1,4-glucan phosphorylase (alpha-1,4-glucan: orthophosphate glucosyltransferase; EC 2.4.1.1) associated with the particulate cell fraction of Streptococcus mitior strain S3 was compared with the soluble maltodextrin phosphorylase that had been previously isolated from the same organism (Walker et al., 1969). The particulate enzyme was more sensitive to the glycogen content of the cell than the soluble euzyme; its activity was highest when the cells were grown under conditions favoring high glycogen storage. Substrate specificities of the two high activity towards endogenous glycogen, whereas low-molecular-weight maltodextrins were the preferred substrates for the soluble phosphorylase. The purification of the particulate phosphorylase included incubation of the particulate fraction in 160 mM sodium phosphate-10 mM sodium citrate-0.1% (wt/vol) Triton X-100 buffer (pH 6.7) and ion-exchange chromatography on diethylamino-ethyl- Sephadex A-50. The purified enzyme was fully soluble. The value for the purification factor was variable and depended on (i) the substrate used and (ii) whether the synthetic or the degradative reaction was being measured. The solubilization resulted in considerable changes in the properties of the phosphorylase: the pH optimum for activity was raised from 6.0 to 7.0-7.5 and the substrate specificity was altered. Consequently, the purified enzyme bore greater similarity to the soluble maltodextrin phosphorylase. The reported results are best explained in terms of a single phosphorylase, the specificity which is determind by its binding state in the cell. The enzyme acts as a glycogen phosphorylase in the particulate state and as a maltodextrin phosphorylase when soluble. The equilibrium between the two forms is related to the glycogen content of the cells."}
{"id": "PMID:6435", "title": "Polygalacturonic acid trans-eliminase in the osmotic shock fluid of Erwinia rubrifaciens: characterization of the purified enzyme and its effect on plant cells.", "content": "An endopolygalacturonic acid trans-eliminase (EC 4.2.2.2), released by osmotic shock of Erwinia rubrifaciens cells, has been purified to near homogeneity (3, 100-fold) by column chromatography on diethylaminoethyl-cellulose, phosphocellulose, and hydroxyapatite-cellulose followed by isoelectric focusing. It has a molecular weight of 41,000, s20,w of 3.09S, an isoelectric point of pH 6.25, pH optimum of 9.5, and a temperature optimum of 37 C and requires Ca2+ with an optimum concentration of 0.5 to 1.0 mM. Mg2+ could not substitute for Ca2+. Tyrosinyl residues seem essential for enzyme catalysis based on rapid inactivation by tetranitromethane. The enzyme prefers unmethylated polygalacturonic acid as the substrate, cleaving alpha-1,4-glycosidic linkages randomly to form unsaturated galacturonides at a Vmax of 1,166 mumol of product/min per mg of protein and a Km of 5 mg of polygalacturonic acid per ml. Over 90% of the enzyme activity is released from osmotically shocked E. rubrifaciens cells. Unlike E. rubrifaciens, trans-eliminase is not released from Erwinia carotovora cells by osmotic shock treatment, but enzyme activity is detected in the culture medium. The release of the enzyme is reduced fivefold by the addition of dibutyryl cyclic adenosine 5'-monophosphate. The hypersensitive reaction in tobacco leaves was induced within 60 min after injection of less than 1 mug of purified E. rubrifaciens trans-eliminase. Single cells of tobacco in suspension culture are readily killed by the enzyme, whereas tobacco protoplasts remain unaffected when treated in the same manner. These results indicate that endopolygalacturonic acid trans-eliminase is a constitutive enzyme possibly located in the periplasmic space of the E. rubrifaciens cell and releases enzyme into the culture medium in the presence of substrate. The release of the enzyme in tobacco tissue and the trans-eliminative cleavage of plant cell wall components may be steps leading to hypersensitivity of the tobacco tissue.", "contents": "Polygalacturonic acid trans-eliminase in the osmotic shock fluid of Erwinia rubrifaciens: characterization of the purified enzyme and its effect on plant cells. An endopolygalacturonic acid trans-eliminase (EC 4.2.2.2), released by osmotic shock of Erwinia rubrifaciens cells, has been purified to near homogeneity (3, 100-fold) by column chromatography on diethylaminoethyl-cellulose, phosphocellulose, and hydroxyapatite-cellulose followed by isoelectric focusing. It has a molecular weight of 41,000, s20,w of 3.09S, an isoelectric point of pH 6.25, pH optimum of 9.5, and a temperature optimum of 37 C and requires Ca2+ with an optimum concentration of 0.5 to 1.0 mM. Mg2+ could not substitute for Ca2+. Tyrosinyl residues seem essential for enzyme catalysis based on rapid inactivation by tetranitromethane. The enzyme prefers unmethylated polygalacturonic acid as the substrate, cleaving alpha-1,4-glycosidic linkages randomly to form unsaturated galacturonides at a Vmax of 1,166 mumol of product/min per mg of protein and a Km of 5 mg of polygalacturonic acid per ml. Over 90% of the enzyme activity is released from osmotically shocked E. rubrifaciens cells. Unlike E. rubrifaciens, trans-eliminase is not released from Erwinia carotovora cells by osmotic shock treatment, but enzyme activity is detected in the culture medium. The release of the enzyme is reduced fivefold by the addition of dibutyryl cyclic adenosine 5'-monophosphate. The hypersensitive reaction in tobacco leaves was induced within 60 min after injection of less than 1 mug of purified E. rubrifaciens trans-eliminase. Single cells of tobacco in suspension culture are readily killed by the enzyme, whereas tobacco protoplasts remain unaffected when treated in the same manner. These results indicate that endopolygalacturonic acid trans-eliminase is a constitutive enzyme possibly located in the periplasmic space of the E. rubrifaciens cell and releases enzyme into the culture medium in the presence of substrate. The release of the enzyme in tobacco tissue and the trans-eliminative cleavage of plant cell wall components may be steps leading to hypersensitivity of the tobacco tissue."}
{"id": "PMID:6436", "title": "Purification of several bacteriolytic enzymes by affinity chromatography on lysozyme-lysate of Micrococcus lysodeikticus cell wall coupled with sepharose.", "content": "Using lysozyme-lysate of Micrococcus lysodeikticus cell wall coupled with Sepharose, several bacteriolytic enzymes were purified from crude preparations of animal and microbial origin. Quail egg-white, human milk and salivary lysozymes [EC 3.2.1.17] were adsorbed onto the adsorbent at pH 5-7 and eluted with 2M NaCl at pH 10. By means of these treatments, lysozymes were purified 20-250 fold with activity recoveries of 60-80%, and the quail lysozyme thus purified was shown to be discelectrophoretically homogeneous. Some bacteriolytic enzymes of microbial origin were also highly purified by using this affinity adsorbent. A bacterial lysozyme from Bacillus sp. ML-208 showed high affinity for the ligand and was not eluted under the conditions mentioned above, but was recovered by elution with 2M guanidine-HCl at pH 5.8, resulting in a 500-fold increase in the specific activity. A Pseudomonas-lytic enzyme from Streptomyces sp. P-51 was easily released from the adsorbent by elution with 0.5M NaCl at pH 5.0. A staphylolytic F2 enzyme from S. griseus S-35 and a chitinase [EC 3.2.1.14] from yam, both of which were completely inert toward M. lysodeikticus cell wall, passed through the adsorbent column. A modified ligand, in which muramic acid and glucosamine residues were N,O-acetylated, failed to adsorb any of these animal and bacterial lysozymes. Some of the enzymatic properties and bacteriolytic action spectra of these purified enzymes are also described in this paper in comparison with those of hen egg-white lysozyme.", "contents": "Purification of several bacteriolytic enzymes by affinity chromatography on lysozyme-lysate of Micrococcus lysodeikticus cell wall coupled with sepharose. Using lysozyme-lysate of Micrococcus lysodeikticus cell wall coupled with Sepharose, several bacteriolytic enzymes were purified from crude preparations of animal and microbial origin. Quail egg-white, human milk and salivary lysozymes [EC 3.2.1.17] were adsorbed onto the adsorbent at pH 5-7 and eluted with 2M NaCl at pH 10. By means of these treatments, lysozymes were purified 20-250 fold with activity recoveries of 60-80%, and the quail lysozyme thus purified was shown to be discelectrophoretically homogeneous. Some bacteriolytic enzymes of microbial origin were also highly purified by using this affinity adsorbent. A bacterial lysozyme from Bacillus sp. ML-208 showed high affinity for the ligand and was not eluted under the conditions mentioned above, but was recovered by elution with 2M guanidine-HCl at pH 5.8, resulting in a 500-fold increase in the specific activity. A Pseudomonas-lytic enzyme from Streptomyces sp. P-51 was easily released from the adsorbent by elution with 0.5M NaCl at pH 5.0. A staphylolytic F2 enzyme from S. griseus S-35 and a chitinase [EC 3.2.1.14] from yam, both of which were completely inert toward M. lysodeikticus cell wall, passed through the adsorbent column. A modified ligand, in which muramic acid and glucosamine residues were N,O-acetylated, failed to adsorb any of these animal and bacterial lysozymes. Some of the enzymatic properties and bacteriolytic action spectra of these purified enzymes are also described in this paper in comparison with those of hen egg-white lysozyme."}
{"id": "PMID:6437", "title": "Enzymatic studies on a cellulase system of Trichoderma viride. III. Transglycosylation properties of two cellulase components of random type.", "content": "Two highly purified cellulases [EC 3.2.1.4], II-A, and II-B, were obtained from the cellulase system of Trichoderma viride. Both cellulases split cellopentaose retaining the beta-configuration of the anomeric carbon atoms in the hydrolysis products at both pH 3.5 and 5.0. The Km values of cellulases II-A and II-B for cellotetraose were different, but their Vmax values were similar and those for cellooligosaccharides increased in parallel with chain length. Both cellulases produced predominantly cellobiose and glucose from various cellulosic substrates as well as from higher cellooligosaccharides. Cellulase II-A preferentially attacked the holoside linkage of rho-nitrophenyl beta-D-cellobioside, whereas cellulase II-B attacked mainly the aglycone linkage of this cellobioside. Both cellulases were found to catalyze the synthesis of cellotriose from rho-nitrophenyl beta-D-cellobioside by transfer of a glucosyl residue, possibly to cellobiose produced in the reaction mixture. They were also found to catalyze the rapid synthesis of cellotetraose from cellobiose, with accompanying formation of cellotriose and glucose, which seemed to be produced by secondary random hydrolysis of the cellotetraose produced. The capacity to synthesize cellotetraose from cellobiose appeared to be greater with cellulase II-B than with cellulase II-A.", "contents": "Enzymatic studies on a cellulase system of Trichoderma viride. III. Transglycosylation properties of two cellulase components of random type. Two highly purified cellulases [EC 3.2.1.4], II-A, and II-B, were obtained from the cellulase system of Trichoderma viride. Both cellulases split cellopentaose retaining the beta-configuration of the anomeric carbon atoms in the hydrolysis products at both pH 3.5 and 5.0. The Km values of cellulases II-A and II-B for cellotetraose were different, but their Vmax values were similar and those for cellooligosaccharides increased in parallel with chain length. Both cellulases produced predominantly cellobiose and glucose from various cellulosic substrates as well as from higher cellooligosaccharides. Cellulase II-A preferentially attacked the holoside linkage of rho-nitrophenyl beta-D-cellobioside, whereas cellulase II-B attacked mainly the aglycone linkage of this cellobioside. Both cellulases were found to catalyze the synthesis of cellotriose from rho-nitrophenyl beta-D-cellobioside by transfer of a glucosyl residue, possibly to cellobiose produced in the reaction mixture. They were also found to catalyze the rapid synthesis of cellotetraose from cellobiose, with accompanying formation of cellotriose and glucose, which seemed to be produced by secondary random hydrolysis of the cellotetraose produced. The capacity to synthesize cellotetraose from cellobiose appeared to be greater with cellulase II-B than with cellulase II-A."}
{"id": "PMID:6438", "title": "Binding of N-acetyl-chitotriose to human lysozyme.", "content": "The interaction of N-acetyl-chitotriose ((GlcNAc)3) with human lysozyme [EC 3.2.1.17] was studied at various pH values by measuring changes in the circular dichroic (CD) band at 294 or 255 nm and the data were compared with the results for hen and turkey lysozymes reported previously (Kuramitsu et al. (1974) J. Biochem.76, 671-683; Kuramitsu et al. (1975) J. Biochem. 77, 291-301). The pH dependence of the binding constant of (GlcNAc)3 to human lysozyme was different from those for hen and turkey lysozymes. The catalytic carboxyls of human lysozyme, Asp 52 and Glu 35, were not perturbed on binding of (GlcNAc)3. This is consistent with the previous findings that the macroscopic pK values of Asp 52 and Glu 35 of human lysozyme are 3.4 and 6.8 at 0.1 ionic strength and 25 degrees and were unchanged on complexing with (GlcNAc)3. An ionizable group with pK 4.5, which participates in the binding of (GlcNAc)3 to hen lysozyme and was assigned  as Asp 101, did not participate in the binding of the saccharide to human lysozyme. Between pH 9 and 11, the binding constants of (GlcNAc)3 to hen lysozyme remained unchanged, whereas perturbation of an ionizable group with pK 10.5 to 10.0 was observed for human lysozyme. This group may be Tyr 62 in the active-site cleft. The binding constants of (GlcNAc)3 to human lysozyme molecules having different microscopic protonation forms, with respect to the catalytic carboxyls, were estimated using the binding constants obtained in the present experiments and the microscopic ionization constants of the catalytic carboxyls obtained previously. All four species of human lysozyme had similar binding constants to (GlcNAc)3. This result is different from those for hen and turkey lysozymes.", "contents": "Binding of N-acetyl-chitotriose to human lysozyme. The interaction of N-acetyl-chitotriose ((GlcNAc)3) with human lysozyme [EC 3.2.1.17] was studied at various pH values by measuring changes in the circular dichroic (CD) band at 294 or 255 nm and the data were compared with the results for hen and turkey lysozymes reported previously (Kuramitsu et al. (1974) J. Biochem.76, 671-683; Kuramitsu et al. (1975) J. Biochem. 77, 291-301). The pH dependence of the binding constant of (GlcNAc)3 to human lysozyme was different from those for hen and turkey lysozymes. The catalytic carboxyls of human lysozyme, Asp 52 and Glu 35, were not perturbed on binding of (GlcNAc)3. This is consistent with the previous findings that the macroscopic pK values of Asp 52 and Glu 35 of human lysozyme are 3.4 and 6.8 at 0.1 ionic strength and 25 degrees and were unchanged on complexing with (GlcNAc)3. An ionizable group with pK 4.5, which participates in the binding of (GlcNAc)3 to hen lysozyme and was assigned  as Asp 101, did not participate in the binding of the saccharide to human lysozyme. Between pH 9 and 11, the binding constants of (GlcNAc)3 to hen lysozyme remained unchanged, whereas perturbation of an ionizable group with pK 10.5 to 10.0 was observed for human lysozyme. This group may be Tyr 62 in the active-site cleft. The binding constants of (GlcNAc)3 to human lysozyme molecules having different microscopic protonation forms, with respect to the catalytic carboxyls, were estimated using the binding constants obtained in the present experiments and the microscopic ionization constants of the catalytic carboxyls obtained previously. All four species of human lysozyme had similar binding constants to (GlcNAc)3. This result is different from those for hen and turkey lysozymes."}
{"id": "PMID:6439", "title": "Kinetics and equilibrium studies on autologous and heterologous recombinations of heavy and light chains of myeloma proteins.", "content": "1. The kinetics of the heterologous recombination reaction of alkylated H chains of a myeloma protein (Jo) with alkylated L chains of another myeloma protein (Ita) were studied by following changes with time in the circular dichroism at 235 nm and the results were compared with those for the autologous recombination of Jo-H chains with Jo-H chains reported previously (T. Azuma et al.(1975) J. Biochem. 77, 473-479 and the preceding paper). The heterologous reaction also followed second-order kinetics. The second-order rate constant (kapp) for heterologous recombination was about seven times smaller than that for autologous recombination at pH 5.5, while they were similar between pH 4.2 and 4.7.  2. The apparent association constants (Kapp) for the reaction, H2+L2=H2L2, were determined by measuring the ellipticities at 235 nm of mixtures of H and L chains in various ratios. The values of Kapp for the autologous and heterologous recombinations were both pH-dependent and changed from 10(6) M-1 at pH 3.9 to 108 M-1 at pH 4.3. Using these values of kapp and Kapp, the half-time for the dissociation of autologous H2L2 to H2 and L2 at pH 4.3 was estimated to be 80 hr.", "contents": "Kinetics and equilibrium studies on autologous and heterologous recombinations of heavy and light chains of myeloma proteins. 1. The kinetics of the heterologous recombination reaction of alkylated H chains of a myeloma protein (Jo) with alkylated L chains of another myeloma protein (Ita) were studied by following changes with time in the circular dichroism at 235 nm and the results were compared with those for the autologous recombination of Jo-H chains with Jo-H chains reported previously (T. Azuma et al.(1975) J. Biochem. 77, 473-479 and the preceding paper). The heterologous reaction also followed second-order kinetics. The second-order rate constant (kapp) for heterologous recombination was about seven times smaller than that for autologous recombination at pH 5.5, while they were similar between pH 4.2 and 4.7.  2. The apparent association constants (Kapp) for the reaction, H2+L2=H2L2, were determined by measuring the ellipticities at 235 nm of mixtures of H and L chains in various ratios. The values of Kapp for the autologous and heterologous recombinations were both pH-dependent and changed from 10(6) M-1 at pH 3.9 to 108 M-1 at pH 4.3. Using these values of kapp and Kapp, the half-time for the dissociation of autologous H2L2 to H2 and L2 at pH 4.3 was estimated to be 80 hr."}
{"id": "PMID:6440", "title": "Studies on phospholipases from Streptomyces. II. Purification and properties of Streptomyces hachijoensis phospholipase D.", "content": "1. Phospholipase D [EC 3.1.4.4] from Streptomyces hachijoensis was purified about 570-fold by column chromatography on DEAE-cellulose and Sephadex G-50 followed by isoelectric focusing. 2. The purified preparation was found to be homogeneous both by immunodiffusion and polyacrylamide disc gel electrophoresis. 3. The isoelectric point was found to be around pH 8.6 and the molecular weight was about 16,000. 4. The enzyme has maximal activity at pH 7.5 at 37 degrees. The optimal temperature is around 50 degrees at pH 7.5, using 20 min incubation. 5. The enzyme was stable at 50 degrees for 90 min. At neutral pH, between 6 and 8, the enzyme retained more than 95% of its activity on 24 hr incubation at 25 degrees. However, the enzyme lost 80% of its activity under the same conditions at pH 4.0. 6. The enzyme was stimulated slightly by Ca2+, Mn2+, and Co2+, and significantly by Triton X-100 and ethyl ether. It was inhibited by Sn2+, Fe2+, Fe3+, Al3+, EDTA, sodium dodecyl sulfate, sodium cholate, and cetylpyridinium chloride. 7. This phospholipase D hydrolyzes phosphatidylethanolamine, phosphatidylcholine, cardiolipin, sphingomyelin, phosphatidylserine, and lysophosphatidylcholine, liberating the corresponding bases. 8. The Km value was 4mM, determined with phosphatidylethanolamine as a substrate.", "contents": "Studies on phospholipases from Streptomyces. II. Purification and properties of Streptomyces hachijoensis phospholipase D. 1. Phospholipase D [EC 3.1.4.4] from Streptomyces hachijoensis was purified about 570-fold by column chromatography on DEAE-cellulose and Sephadex G-50 followed by isoelectric focusing. 2. The purified preparation was found to be homogeneous both by immunodiffusion and polyacrylamide disc gel electrophoresis. 3. The isoelectric point was found to be around pH 8.6 and the molecular weight was about 16,000. 4. The enzyme has maximal activity at pH 7.5 at 37 degrees. The optimal temperature is around 50 degrees at pH 7.5, using 20 min incubation. 5. The enzyme was stable at 50 degrees for 90 min. At neutral pH, between 6 and 8, the enzyme retained more than 95% of its activity on 24 hr incubation at 25 degrees. However, the enzyme lost 80% of its activity under the same conditions at pH 4.0. 6. The enzyme was stimulated slightly by Ca2+, Mn2+, and Co2+, and significantly by Triton X-100 and ethyl ether. It was inhibited by Sn2+, Fe2+, Fe3+, Al3+, EDTA, sodium dodecyl sulfate, sodium cholate, and cetylpyridinium chloride. 7. This phospholipase D hydrolyzes phosphatidylethanolamine, phosphatidylcholine, cardiolipin, sphingomyelin, phosphatidylserine, and lysophosphatidylcholine, liberating the corresponding bases. 8. The Km value was 4mM, determined with phosphatidylethanolamine as a substrate."}
{"id": "PMID:6441", "title": "Pyridine-2, 6-dicarboxylic acid (dipicolinic acid) formation in Bacillus subtilis. II Non-enzymatic and enzymatic formations of dipicolinic acid from alpha, epsilon-diketopimelic acid and ammonia.", "content": "Non-enzymatic formation of dipicolinic acid (DPA) from diketopimelic acid and ammonia was clearly demonstrated using a new method for DPA analysis. The reaction rates of DPA formation were almost the same under aerobic and anaerobic conditions. Nearly equimolecular quantities of DPA and tetrahydrodipicolinic acid were detected in spontaneous reaction mixture. The spontaneous reaction seemed to be due to dismutation of dihydrodipicolinic acid, resulting in DPA and tetrahydrodipicolinic acid. The apparent optimum pH of the spontaneous reaction was 8.2 and the maximal rate of DPA formation was observed with a 1 : 4 molar ratio of diketopimelic acid to ammonia. The rate of the spontaneous reaction was stimulated by ferrous sulfate, FMN, and riboflavin. Dihydrodipicolinate reductase catalyzes the reduction of dihydrodipicolinate, prepared from pyruvate and aspartic beta-semialdehyde, with NADPH as reductant. The reductase was isolated from Bacillus subtilis, and found to stimulate DPA formation from diketopimelic acid and ammonia. The enzymatic DPA formation was absolutely dependent on oxygen, and optimum pH was 6.4. The catalytic action of the enzyme was similar to that of the oxidase. Possible mechanisms of DPA formation from diketopimelic acid and ammonia are proposed.", "contents": "Pyridine-2, 6-dicarboxylic acid (dipicolinic acid) formation in Bacillus subtilis. II Non-enzymatic and enzymatic formations of dipicolinic acid from alpha, epsilon-diketopimelic acid and ammonia. Non-enzymatic formation of dipicolinic acid (DPA) from diketopimelic acid and ammonia was clearly demonstrated using a new method for DPA analysis. The reaction rates of DPA formation were almost the same under aerobic and anaerobic conditions. Nearly equimolecular quantities of DPA and tetrahydrodipicolinic acid were detected in spontaneous reaction mixture. The spontaneous reaction seemed to be due to dismutation of dihydrodipicolinic acid, resulting in DPA and tetrahydrodipicolinic acid. The apparent optimum pH of the spontaneous reaction was 8.2 and the maximal rate of DPA formation was observed with a 1 : 4 molar ratio of diketopimelic acid to ammonia. The rate of the spontaneous reaction was stimulated by ferrous sulfate, FMN, and riboflavin. Dihydrodipicolinate reductase catalyzes the reduction of dihydrodipicolinate, prepared from pyruvate and aspartic beta-semialdehyde, with NADPH as reductant. The reductase was isolated from Bacillus subtilis, and found to stimulate DPA formation from diketopimelic acid and ammonia. The enzymatic DPA formation was absolutely dependent on oxygen, and optimum pH was 6.4. The catalytic action of the enzyme was similar to that of the oxidase. Possible mechanisms of DPA formation from diketopimelic acid and ammonia are proposed."}
{"id": "PMID:6442", "title": "Trinitrophenylation of nucleic acids and their constituents.", "content": "1. Under relatively mild conditions, nucleic acids and their constituents were trinitrophenylated with 2,4,6-trinitrobenzenesulfonate (TNBS) in aqueous solution (pH 8-11), yielding reddish-orange trinitrophenyl (TNP) derivatives. Guanine residues were trinitrophenylated on the base residues at the 2-amino group (N2-TNP derivatives), and in addition, 2'- and 3'-hydroxyl groups of the ribose moieties of nucleosides or nucleotides were trinitrophenylated to form Meisenheimer complexes. 2. The preparation of TNP derivatives (N2-TNP-guanine, -guanosine, N2, O-bis-TNP-guanosine, O-TNP-guanosine, -adenosine, -cytidine , and -uridine), their rates of formation, absorption spectra (UV, visible, and infrared), molar extinction coefficients, Rf value, electrophoretic mobilities, and stability in acid or alkaline solution, are presented. 3. Trinitrophenylation of several kinds of nucleic acid was investigated. Calf thymus DNA and yeast transfer RNA showed a resistance to trinitrophenylation compared to guanosine 3'(2')-phosphate, yeast RNA or denatured calf thymus DNA. TNP-RNA showed resistance to the action of ribonucleases T1 and T2 [EC 3.1.4.8 and 3.1.4.23]. 4. Trinitrophenylation reactions using 2,4,6-trinitrochlorobenzene and 2,4,6-trinitrofluorobenzene were compared with that using TNBS as regards specificity and reaction rate.", "contents": "Trinitrophenylation of nucleic acids and their constituents. 1. Under relatively mild conditions, nucleic acids and their constituents were trinitrophenylated with 2,4,6-trinitrobenzenesulfonate (TNBS) in aqueous solution (pH 8-11), yielding reddish-orange trinitrophenyl (TNP) derivatives. Guanine residues were trinitrophenylated on the base residues at the 2-amino group (N2-TNP derivatives), and in addition, 2'- and 3'-hydroxyl groups of the ribose moieties of nucleosides or nucleotides were trinitrophenylated to form Meisenheimer complexes. 2. The preparation of TNP derivatives (N2-TNP-guanine, -guanosine, N2, O-bis-TNP-guanosine, O-TNP-guanosine, -adenosine, -cytidine , and -uridine), their rates of formation, absorption spectra (UV, visible, and infrared), molar extinction coefficients, Rf value, electrophoretic mobilities, and stability in acid or alkaline solution, are presented. 3. Trinitrophenylation of several kinds of nucleic acid was investigated. Calf thymus DNA and yeast transfer RNA showed a resistance to trinitrophenylation compared to guanosine 3'(2')-phosphate, yeast RNA or denatured calf thymus DNA. TNP-RNA showed resistance to the action of ribonucleases T1 and T2 [EC 3.1.4.8 and 3.1.4.23]. 4. Trinitrophenylation reactions using 2,4,6-trinitrochlorobenzene and 2,4,6-trinitrofluorobenzene were compared with that using TNBS as regards specificity and reaction rate."}
{"id": "PMID:6445", "title": "Activation of mouse splenic lymphocyte guanylate cyclase by calcium ion.", "content": "The guanosine 3',5'-cyclic monophosphate (cGMP) level in the mouse splenic lymphocytes was increased about 2- to 3-fold by concanavalin A. This increase was completely dependent on the presence of Ca2+ in the medium. Homogenates of mouse splenic lymphocytes contained significant guanylate cyclase [EC 4.6.1.2] activity in both the 105,000 X g (60 min) particulate and supernatant fractions and both fractions required Mn2+ for full activity. Calcium ion (3mM) activated soluble guanylate cyclase 3-fold at a relatively low concentration of Mn2+ (less than 1mM) but inhibited the particulate enzyme slightly at all Mn2+ concentrations tested. Concanavalin A itself did not stimulate either fraction of guanylate cyclase. Thus these results suggest that elevation of the cGMP level in lymphocytes by concanavalin A might be brought about by stimulation of Ca2+ uptake and activation of soluble guanylate cyclase by the latter.", "contents": "Activation of mouse splenic lymphocyte guanylate cyclase by calcium ion. The guanosine 3',5'-cyclic monophosphate (cGMP) level in the mouse splenic lymphocytes was increased about 2- to 3-fold by concanavalin A. This increase was completely dependent on the presence of Ca2+ in the medium. Homogenates of mouse splenic lymphocytes contained significant guanylate cyclase [EC 4.6.1.2] activity in both the 105,000 X g (60 min) particulate and supernatant fractions and both fractions required Mn2+ for full activity. Calcium ion (3mM) activated soluble guanylate cyclase 3-fold at a relatively low concentration of Mn2+ (less than 1mM) but inhibited the particulate enzyme slightly at all Mn2+ concentrations tested. Concanavalin A itself did not stimulate either fraction of guanylate cyclase. Thus these results suggest that elevation of the cGMP level in lymphocytes by concanavalin A might be brought about by stimulation of Ca2+ uptake and activation of soluble guanylate cyclase by the latter."}
{"id": "PMID:6446", "title": "Rat intestinal brush border membrane peptidases. II. Enzymatic properties, immunochemistry, and interactions with lectins of two different forms of the enzyme.", "content": "The properties of two purified peptidases derived from the intestinal brush border membrane of the rat have been investigated. The pH optima, heat stabilities, substrate specificities, and metal ion requirements of the two enzymes and the effects of inhibitors on their activities were nearly identical. The isoenzymes catalyzed the hydrolysis of a wide range of peptides containing from 2 to 8 amino acid residues. The enzymes are aminopeptidases; no evidence for carboxypeptidase or endopeptidase activity was found. For hydrolysis, there appears to be an absolute requirement for an L-amino acid at the NH2-terminus of the peptide substrate. There was a similar but less absolute requirement for the penultimate NH2-terminal amino acid. Thus, although peptides of the type L-aminoacyl-L-proline, L-aminoacyl-L-prolyl-(L-amino acid)n, or L-aminoacyl-D-amino acid were not hydrolyzed, L-leucyl-beta-naphthylamide could be utilized as a substrate. The enzymes appeared to be metalloenzymes in that metal ion-chelating agents could inhibit their activities. Co2+ partially restored the activities lost by chelation. Immunodiffusion studies showed that the two enzymes were immunologically identical. The antipeptidase antisera were specific for the enzymes and did not react with other constituents of the intestinal cell. Both enzymes have binding sites for the lectin phytohemagglutinin which recognizes N-acetylgalactosamine residues located at or near the terminal positions of glycoprotein carbohydrate chains. Both the lectin and the antibodies inhibited enzyme activities, but the mechanisms of inhibition appeared to be different.", "contents": "Rat intestinal brush border membrane peptidases. II. Enzymatic properties, immunochemistry, and interactions with lectins of two different forms of the enzyme. The properties of two purified peptidases derived from the intestinal brush border membrane of the rat have been investigated. The pH optima, heat stabilities, substrate specificities, and metal ion requirements of the two enzymes and the effects of inhibitors on their activities were nearly identical. The isoenzymes catalyzed the hydrolysis of a wide range of peptides containing from 2 to 8 amino acid residues. The enzymes are aminopeptidases; no evidence for carboxypeptidase or endopeptidase activity was found. For hydrolysis, there appears to be an absolute requirement for an L-amino acid at the NH2-terminus of the peptide substrate. There was a similar but less absolute requirement for the penultimate NH2-terminal amino acid. Thus, although peptides of the type L-aminoacyl-L-proline, L-aminoacyl-L-prolyl-(L-amino acid)n, or L-aminoacyl-D-amino acid were not hydrolyzed, L-leucyl-beta-naphthylamide could be utilized as a substrate. The enzymes appeared to be metalloenzymes in that metal ion-chelating agents could inhibit their activities. Co2+ partially restored the activities lost by chelation. Immunodiffusion studies showed that the two enzymes were immunologically identical. The antipeptidase antisera were specific for the enzymes and did not react with other constituents of the intestinal cell. Both enzymes have binding sites for the lectin phytohemagglutinin which recognizes N-acetylgalactosamine residues located at or near the terminal positions of glycoprotein carbohydrate chains. Both the lectin and the antibodies inhibited enzyme activities, but the mechanisms of inhibition appeared to be different."}
{"id": "PMID:6447", "title": "Transport of riboflavin into yeast cells.", "content": "Riboflavin-requiring mutants of Saccharomyces cerevisiae are able to transport 14C-labeled riboflavin into the cell, although no significant transport is seen in commercial yeast or in the parent strain from which the mutants were derived. Transport activity is greatest in the early to mid-log phase of anaerobic growth and declines sharply in the late log phase. In aerobically grown cells activity is substantially lower at all stages of growth. In the assay devised for its measurement, transport activity shows a sharp pH optimum at pH 7.5, a strong temperature dependence (EA = 23,100 cal/mol), and saturation kinetics with respect to riboflavin (Km = 15 muM), characteristics consistent with a carrier-mediated mechanism. Monovalent inorganic cations, particularly K+ and Rb+, stimulate riboflavin uptake, while certain organic cations are inhibitory. Besides riboflavin only 7-methylriboflavin, 8-methylriboflavin, and 5-deazaflavin have been found to serve as substrates, while lumiflavin, tetraacetylriboflavin, and N10-[4'-carboxybutyl]-7,8-dimethylisoalloxazine do not, although a number of flavin analogs in which the ribityl side chain is modified are good competitive inhibitors of riboflavin uptake. Compounds resembling the ribityl side chain, such as sugars and sugar alcohols, do not inhibit. An apparent inhibition of uptake by D-glucose, D-mannose, and D-fructose, which develops in the course of assay, proved to result from stimulation of an opposing process, the release of riboflavin from the cells.", "contents": "Transport of riboflavin into yeast cells. Riboflavin-requiring mutants of Saccharomyces cerevisiae are able to transport 14C-labeled riboflavin into the cell, although no significant transport is seen in commercial yeast or in the parent strain from which the mutants were derived. Transport activity is greatest in the early to mid-log phase of anaerobic growth and declines sharply in the late log phase. In aerobically grown cells activity is substantially lower at all stages of growth. In the assay devised for its measurement, transport activity shows a sharp pH optimum at pH 7.5, a strong temperature dependence (EA = 23,100 cal/mol), and saturation kinetics with respect to riboflavin (Km = 15 muM), characteristics consistent with a carrier-mediated mechanism. Monovalent inorganic cations, particularly K+ and Rb+, stimulate riboflavin uptake, while certain organic cations are inhibitory. Besides riboflavin only 7-methylriboflavin, 8-methylriboflavin, and 5-deazaflavin have been found to serve as substrates, while lumiflavin, tetraacetylriboflavin, and N10-[4'-carboxybutyl]-7,8-dimethylisoalloxazine do not, although a number of flavin analogs in which the ribityl side chain is modified are good competitive inhibitors of riboflavin uptake. Compounds resembling the ribityl side chain, such as sugars and sugar alcohols, do not inhibit. An apparent inhibition of uptake by D-glucose, D-mannose, and D-fructose, which develops in the course of assay, proved to result from stimulation of an opposing process, the release of riboflavin from the cells."}
{"id": "PMID:6448", "title": "Soluble enzyme system for vitamin K-dependent carboxylation.", "content": "The vitamin K-dependent carboxylating system has been solubilized by Lubrol PX or Triton X-100 treatment of vitamin K-deficient rat liver microsomes. As obtained from vitamin K-deficient rat liver, this soluble preparation is dependent upon the in vitro addition of vitamin K1 for carboxylating activity. The enzyme system is complex and is dependent upon NADH and dithiothreitol for maximum activity. While detergents used to solubilize the enzyme complex do markedly inhibit the activity of the system, the solubilized system is still highly responsive to vitamin K addition and can be used for further study of the carboxylating enzyme system. The requirement for dithiothreitol and the inhibition by p-hydroxymercuribenzoate indicate the involvement of an --SH enzyme in the carboxylating system.", "contents": "Soluble enzyme system for vitamin K-dependent carboxylation. The vitamin K-dependent carboxylating system has been solubilized by Lubrol PX or Triton X-100 treatment of vitamin K-deficient rat liver microsomes. As obtained from vitamin K-deficient rat liver, this soluble preparation is dependent upon the in vitro addition of vitamin K1 for carboxylating activity. The enzyme system is complex and is dependent upon NADH and dithiothreitol for maximum activity. While detergents used to solubilize the enzyme complex do markedly inhibit the activity of the system, the solubilized system is still highly responsive to vitamin K addition and can be used for further study of the carboxylating enzyme system. The requirement for dithiothreitol and the inhibition by p-hydroxymercuribenzoate indicate the involvement of an --SH enzyme in the carboxylating system."}
{"id": "PMID:6449", "title": "Glutamate synthase. Properties of the glutamine-dependent activity.", "content": "Properties of glutamine-dependent glutamate synthase have been investigated using homogeneous enzyme from Escherichia coli K-12. In contrast to results with enzyme from E. coli strain B (Miller, R. E., and Stadtman, E. R. (1972) J. Biol. Chem. 247, 7407-7419), this enzyme catalyzes NH3-dependent glutamate synthase activity. Selective inactivation of glutamine-dependent activity was obtained by treatment with the glutamine analog. L-2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Inactivation by chloroketone exhibited saturation kinetics; glutamine reduced the rate of inactivation and exhibited competitive kinetics. Iodoacetamide, other alpha-halocarbonyl compounds, and sulfhydryl reagents gave similar selective inactivation of glutamine-dependent activity. Saturation kinetics were not obtained for inactivation by iodoacetamide but protection by glutamine exhibited competitive kinetics. The stoichiometry for alkylation by chloroketone and iodoacetamide was approximately 1 residue per protomer of molecular weight approximately 188,000. The single residue alkylated with iodo [1-14C]acetamide was identified as cysteine by isolation of S-carboxymethylcysteine. This active site cysteine is in the large subunit of molecular weight approximately 153,000. The active site cysteine was sensitive to oxidation by H2O2 generated by autooxidation of reduced flavin and resulted in selective inactivation of glutamine-dependent enzyme activity. Similar to other glutamine amidotransferases, glutamate synthase exhibits glutaminase activity. Glutaminase activity is dependent upon the functional integrity of the active site cysteine but is not wholly dependent upon the flavin and non-heme iron. Collectively, these results demonstrate that glutamate synthase is similar to other glutamine amidotransferases with respect to distinct sites for glutamine and NH3 utilization and in the obligatory function of an active site cysteine residue for glutamine utilization.", "contents": "Glutamate synthase. Properties of the glutamine-dependent activity. Properties of glutamine-dependent glutamate synthase have been investigated using homogeneous enzyme from Escherichia coli K-12. In contrast to results with enzyme from E. coli strain B (Miller, R. E., and Stadtman, E. R. (1972) J. Biol. Chem. 247, 7407-7419), this enzyme catalyzes NH3-dependent glutamate synthase activity. Selective inactivation of glutamine-dependent activity was obtained by treatment with the glutamine analog. L-2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Inactivation by chloroketone exhibited saturation kinetics; glutamine reduced the rate of inactivation and exhibited competitive kinetics. Iodoacetamide, other alpha-halocarbonyl compounds, and sulfhydryl reagents gave similar selective inactivation of glutamine-dependent activity. Saturation kinetics were not obtained for inactivation by iodoacetamide but protection by glutamine exhibited competitive kinetics. The stoichiometry for alkylation by chloroketone and iodoacetamide was approximately 1 residue per protomer of molecular weight approximately 188,000. The single residue alkylated with iodo [1-14C]acetamide was identified as cysteine by isolation of S-carboxymethylcysteine. This active site cysteine is in the large subunit of molecular weight approximately 153,000. The active site cysteine was sensitive to oxidation by H2O2 generated by autooxidation of reduced flavin and resulted in selective inactivation of glutamine-dependent enzyme activity. Similar to other glutamine amidotransferases, glutamate synthase exhibits glutaminase activity. Glutaminase activity is dependent upon the functional integrity of the active site cysteine but is not wholly dependent upon the flavin and non-heme iron. Collectively, these results demonstrate that glutamate synthase is similar to other glutamine amidotransferases with respect to distinct sites for glutamine and NH3 utilization and in the obligatory function of an active site cysteine residue for glutamine utilization."}
{"id": "PMID:6450", "title": "Properties of apoglutamate synthase and comparison with glutamate dehydrogenase.", "content": "Glutamate synthase from Escherichia coli K-12 exhibits NH3-dependent activity. NH3-dependent activity is increased approximately 5-fold in apoglutamate synthase lacking flavin and non-heme iron. Whereas glutamine plus 2-oxoglutarate have the capacity to reoxidize the chemically reduced flavoenzyme, no such reoxidation is obtained with 2-oxoglutarate plus NH3. These results establish that the glutamine- and NH3-dependent syntheses of glutamate occur by different pathways of electron transfer from NADPH. The NH3-dependent activity of native and apoglutamate synthase exhibits similar catalytic properties. Some properties of apoglutamate synthase are similar to those of glutamate dehydrogenase. These properties include pH optima for synthesis and oxidative deamination of glutamate, inactivation by alkylating reagents and p-mercuribenzoate, an enhanced rate of inactivation by alkylating reagents and p-mercuribenzoate at low pH, 2-oxoglutarate protection against inactivation by p-mercuribenzoate, and reactivation of p-mercuribenzoate-treated enzyme by 2-mercaptoethanol. 2-Oxoglutarate protects against alkylation of glutamate synthase by iodo [1-14C]acetamide and reduces incorporation of methyl [1-14C]carboxamide into the small subunit of the enzyme.", "contents": "Properties of apoglutamate synthase and comparison with glutamate dehydrogenase. Glutamate synthase from Escherichia coli K-12 exhibits NH3-dependent activity. NH3-dependent activity is increased approximately 5-fold in apoglutamate synthase lacking flavin and non-heme iron. Whereas glutamine plus 2-oxoglutarate have the capacity to reoxidize the chemically reduced flavoenzyme, no such reoxidation is obtained with 2-oxoglutarate plus NH3. These results establish that the glutamine- and NH3-dependent syntheses of glutamate occur by different pathways of electron transfer from NADPH. The NH3-dependent activity of native and apoglutamate synthase exhibits similar catalytic properties. Some properties of apoglutamate synthase are similar to those of glutamate dehydrogenase. These properties include pH optima for synthesis and oxidative deamination of glutamate, inactivation by alkylating reagents and p-mercuribenzoate, an enhanced rate of inactivation by alkylating reagents and p-mercuribenzoate at low pH, 2-oxoglutarate protection against inactivation by p-mercuribenzoate, and reactivation of p-mercuribenzoate-treated enzyme by 2-mercaptoethanol. 2-Oxoglutarate protects against alkylation of glutamate synthase by iodo [1-14C]acetamide and reduces incorporation of methyl [1-14C]carboxamide into the small subunit of the enzyme."}
{"id": "PMID:6451", "title": "Mechanism of the irreversible inhibition of aspartate aminotransferase by the bacterial toxin L-2-amino-4-methoxy-trans-3-butenoic acid.", "content": "The naturally occurring toxin L-2-amino-4-methoxy-trans-3-butenoic (AMB) acid irreversibly inhibits pyridoxal phosphate-linked aspartate aminotransferase. The inhibitor is a substrate for the enzyme, and as such is converted into a highly reactive intermediate which chemically reacts with an active site residue, thus irreversibly inactivating the enzyme. Enzymological and model studies on AMB are presented which enable one to determine the precise mechanism of action of this toxin. The mechanism involves Schiff base formation between the enzyme and toxin followed by alpha-C--H bond cleavage and aldimine isomerization to generate a bifunctional Michael acceptor. This molecule alkylates an active site residue by an addition and elimination route.", "contents": "Mechanism of the irreversible inhibition of aspartate aminotransferase by the bacterial toxin L-2-amino-4-methoxy-trans-3-butenoic acid. The naturally occurring toxin L-2-amino-4-methoxy-trans-3-butenoic (AMB) acid irreversibly inhibits pyridoxal phosphate-linked aspartate aminotransferase. The inhibitor is a substrate for the enzyme, and as such is converted into a highly reactive intermediate which chemically reacts with an active site residue, thus irreversibly inactivating the enzyme. Enzymological and model studies on AMB are presented which enable one to determine the precise mechanism of action of this toxin. The mechanism involves Schiff base formation between the enzyme and toxin followed by alpha-C--H bond cleavage and aldimine isomerization to generate a bifunctional Michael acceptor. This molecule alkylates an active site residue by an addition and elimination route."}
{"id": "PMID:6452", "title": "The activating system of chitin synthetase from Saccharomyces cerevisiae. Purification and properties of the activating factor.", "content": "The yeast proteinase that causes activation of the chitin synthetase zymogen has been purified by a procedure that includes affinity chromatography on an agarose column to which the proteinaceous inhibitor of the enzyme had been covalently attached. The purified enzyme yielded a single band upon disc gel electrophoresis at pH 4.5 in the presence of urea. At the same pH, but without urea, a faint band was detected in coincidence with enzymatic activity, whereas at pH 9.5, either in the absence or in the presence of sodium dodecyl sulfate, no protein zone could be seen. From sedimentation and gel filtration data, a molecular weight of 44,000 was estimated. The proteinase was active within a wide range of pH values, with an optimum between pH 6.5 AND 7. Titraton of the activity with the protein inhibitor from yeast required 1 mol of inhibitor/mol of enzyme. A similar result was obtained with phenylmethylsulfonyl fluoride, an indication that 1 serine residue is required for enzymatic activity. The enzyme exhibited hydrolytic activity with several proteins and esterolytic activity with many synthetic substrates, including benzoylarginine ethyl ester and acetyltyrosine ethyl ester.A comparison of the properties of the enzyme with those of known yeast proteinases led to the conclusion that the chitin synthestase activating factor is identical with the enzyme previously designated as proteinase B (EC 3.4.22.9). This is the first time that a homogeneous preparation of proteinase B has been obtained and characterized.", "contents": "The activating system of chitin synthetase from Saccharomyces cerevisiae. Purification and properties of the activating factor. The yeast proteinase that causes activation of the chitin synthetase zymogen has been purified by a procedure that includes affinity chromatography on an agarose column to which the proteinaceous inhibitor of the enzyme had been covalently attached. The purified enzyme yielded a single band upon disc gel electrophoresis at pH 4.5 in the presence of urea. At the same pH, but without urea, a faint band was detected in coincidence with enzymatic activity, whereas at pH 9.5, either in the absence or in the presence of sodium dodecyl sulfate, no protein zone could be seen. From sedimentation and gel filtration data, a molecular weight of 44,000 was estimated. The proteinase was active within a wide range of pH values, with an optimum between pH 6.5 AND 7. Titraton of the activity with the protein inhibitor from yeast required 1 mol of inhibitor/mol of enzyme. A similar result was obtained with phenylmethylsulfonyl fluoride, an indication that 1 serine residue is required for enzymatic activity. The enzyme exhibited hydrolytic activity with several proteins and esterolytic activity with many synthetic substrates, including benzoylarginine ethyl ester and acetyltyrosine ethyl ester.A comparison of the properties of the enzyme with those of known yeast proteinases led to the conclusion that the chitin synthestase activating factor is identical with the enzyme previously designated as proteinase B (EC 3.4.22.9). This is the first time that a homogeneous preparation of proteinase B has been obtained and characterized."}
{"id": "PMID:6453", "title": "Accleration of autooxidation of human oxyhemoglobin by aniline and its relation to hemoglobin-catalyzed aniline hydroxylation.", "content": "Changes in the ultraviolet/visible spectrum of human oxyferrohemoglobin upon addition of aniline were indicative of a concentration-dependent interaction of aniline with hemoglobin, resulting in accelerated autooxidation of the hemoprotein. Oxygen was found to markedly inhibit this interaction of aniline with oxyhemoglobin. The dependence of the rate of autooxidation on aniline concentration followed saturation kinetics and showed a half-maximal response at 8 mM aniline. This value is equal to the value of Km for aniline as substrate for the O2-dependent, hemoglobin-catalyzed hydroxylation reaction which yields p-aminophenol (Mieyal, J. J., Ackerman, R.S., Blumer, J.L., and Freeman, L.S. (1976) J. Biol. Chem. 241, 3436-3441). Thus, an aniline-oxyhemoglobin complex is implicated in the overall catalytic reaction. No detectable p-aminophenol was formed when aniline was combined with oxyhemoglobin in the absence of an electron donor, but hydroxylation of aniline does occur when NADPH, NADPH plus P-450 reductase, or Na2S2O4 are also added.", "contents": "Accleration of autooxidation of human oxyhemoglobin by aniline and its relation to hemoglobin-catalyzed aniline hydroxylation. Changes in the ultraviolet/visible spectrum of human oxyferrohemoglobin upon addition of aniline were indicative of a concentration-dependent interaction of aniline with hemoglobin, resulting in accelerated autooxidation of the hemoprotein. Oxygen was found to markedly inhibit this interaction of aniline with oxyhemoglobin. The dependence of the rate of autooxidation on aniline concentration followed saturation kinetics and showed a half-maximal response at 8 mM aniline. This value is equal to the value of Km for aniline as substrate for the O2-dependent, hemoglobin-catalyzed hydroxylation reaction which yields p-aminophenol (Mieyal, J. J., Ackerman, R.S., Blumer, J.L., and Freeman, L.S. (1976) J. Biol. Chem. 241, 3436-3441). Thus, an aniline-oxyhemoglobin complex is implicated in the overall catalytic reaction. No detectable p-aminophenol was formed when aniline was combined with oxyhemoglobin in the absence of an electron donor, but hydroxylation of aniline does occur when NADPH, NADPH plus P-450 reductase, or Na2S2O4 are also added."}
{"id": "PMID:6454", "title": "Regulation of glutaminase B in Escherichia coli. I. Purification, properties, and cold lability.", "content": "Escherichia coli contains two glutaminases, A and B, with pH optima below pH 5 and above pH 7, respectively. Neither glutaminase A nor B is released from E. coli by osmotic shock. Glutaminase B has been purified 6,000-fold and the purified preparation is estimated to contain about 40% glutaminase B. The enzyme has a molecular weight of 90,000 and an isoelectric point of 5.4. Glutaminase B exhibits a broad pH optimum between 7.1 and 9.0. Only L-glutamine is deamidated by glutaminase B, L-asparagine and D-glutamine are not deamidated. The substrate saturation curve for glutaminase B shows an intermediary plateau region. Like many regulatory enzymes, glutaminase B is cold-labile. The enzyme is inactivated by cooling and activated by warming; both processes are first order with respect to time. The activation energy for activation by warming was calculated to be 5900 cal/mol. Activation by warming increased the Vmax and decreased the S0.5 for L-glutamine, but did not alter the molecular weight of the catalytically active enzyme. Borate and glutamate protected glutaminase B from inactivation by cold.", "contents": "Regulation of glutaminase B in Escherichia coli. I. Purification, properties, and cold lability. Escherichia coli contains two glutaminases, A and B, with pH optima below pH 5 and above pH 7, respectively. Neither glutaminase A nor B is released from E. coli by osmotic shock. Glutaminase B has been purified 6,000-fold and the purified preparation is estimated to contain about 40% glutaminase B. The enzyme has a molecular weight of 90,000 and an isoelectric point of 5.4. Glutaminase B exhibits a broad pH optimum between 7.1 and 9.0. Only L-glutamine is deamidated by glutaminase B, L-asparagine and D-glutamine are not deamidated. The substrate saturation curve for glutaminase B shows an intermediary plateau region. Like many regulatory enzymes, glutaminase B is cold-labile. The enzyme is inactivated by cooling and activated by warming; both processes are first order with respect to time. The activation energy for activation by warming was calculated to be 5900 cal/mol. Activation by warming increased the Vmax and decreased the S0.5 for L-glutamine, but did not alter the molecular weight of the catalytically active enzyme. Borate and glutamate protected glutaminase B from inactivation by cold."}
{"id": "PMID:6455", "title": "Effects of divalent cation ionophore A23187 on potassium permeability of rat erythrocytes.", "content": "A23187 transports calcium rapidly into rat erythrocytes, apparently by an electroneutral exchange for intracellular magnesium and protons. When red cells are incubated in the absence of any added divalent cations, A23187 transports internal magnesium out of the cells, in exchange for extracellular protons. Magnesium uptake into erythrocytes is produced by A23187, providing the extracellular concentration of this cation exceeds intracellular levels, and the ionophore also transports strontium, but not barium, into red cells. A23187 produces a rapid and extensive loss of intracellular potassium from erythrocytes during uptake of calcium or strontium, but not magnesium. When red cells are incubated in the absence of any exogenous divalent cations, A23187 still produces a potassium efflux and this is inhibited completely by small amounts of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and restored by the addition of calcium in excess of the chelator. Although EDTA enhances the extent of magnesium release from erythrocytes incubated with A23187, it prevents the potassium efflux. Dipyridamole and 4-acetamid-4'-isothiocyano-stilbene-2,5'-disulfonic acid, which decrease chloride premeability of erythrocytes, inhibit the A23187-induced potassium loss from red cells. Rutamycin, peliomycin, venturicidin, and A23668B also inhibit potassium efflux from intact cells incubated with A23187, but this effect is not correlated with their abilities to inhibit various ATPases in red cell membrane preparations. It is concluded that A23187 does not transport potassium directly across the erythrocyte plasma membrane, but permits small amounts of endogenous calcium to interact with some membrane component to enhance potassium permeability of the cell.", "contents": "Effects of divalent cation ionophore A23187 on potassium permeability of rat erythrocytes. A23187 transports calcium rapidly into rat erythrocytes, apparently by an electroneutral exchange for intracellular magnesium and protons. When red cells are incubated in the absence of any added divalent cations, A23187 transports internal magnesium out of the cells, in exchange for extracellular protons. Magnesium uptake into erythrocytes is produced by A23187, providing the extracellular concentration of this cation exceeds intracellular levels, and the ionophore also transports strontium, but not barium, into red cells. A23187 produces a rapid and extensive loss of intracellular potassium from erythrocytes during uptake of calcium or strontium, but not magnesium. When red cells are incubated in the absence of any exogenous divalent cations, A23187 still produces a potassium efflux and this is inhibited completely by small amounts of ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and restored by the addition of calcium in excess of the chelator. Although EDTA enhances the extent of magnesium release from erythrocytes incubated with A23187, it prevents the potassium efflux. Dipyridamole and 4-acetamid-4'-isothiocyano-stilbene-2,5'-disulfonic acid, which decrease chloride premeability of erythrocytes, inhibit the A23187-induced potassium loss from red cells. Rutamycin, peliomycin, venturicidin, and A23668B also inhibit potassium efflux from intact cells incubated with A23187, but this effect is not correlated with their abilities to inhibit various ATPases in red cell membrane preparations. It is concluded that A23187 does not transport potassium directly across the erythrocyte plasma membrane, but permits small amounts of endogenous calcium to interact with some membrane component to enhance potassium permeability of the cell."}
{"id": "PMID:6456", "title": "Yeast alpha-isopropylmalate isomerase. Factors affecting stability and enzyme activity.", "content": "Yeast alpha-isopropylmalate isomerase was found to be markedly stabilized by high concentrations of glycerol and (NH4)2SO4. Such conditions of high ionic strength inhibited the enzyme, stabilized the enzyme to heat, and affected kinetic parameters. The isomerase was found to exhibit ionic strength-dependent hysteresis when enzyme, totally but reversibly inhibited by storage under conditions of high ionic strength of (NH4)2SO4, was transferred to a lower concentration of (NH4)2SO4. Alpha-Isopropylmalate isomerase was found to be sensitive to KCN and certain other chelators. The inactivation by KCN was prevented by high concentrations of (NH4)2SO4. These observations implicated a metal involvement but the nature of the metal was not revealed. The metal involvement and some of the other properties of alpha-isopropylmalate isomerase reveal a similarity to aconitase. The similarities in properties between the isomerase and aconitase are summarized. Studies of yeast alpha-isopropylmalate isomerase indicated that it is a single polypeptide of about Mr = 90,000.", "contents": "Yeast alpha-isopropylmalate isomerase. Factors affecting stability and enzyme activity. Yeast alpha-isopropylmalate isomerase was found to be markedly stabilized by high concentrations of glycerol and (NH4)2SO4. Such conditions of high ionic strength inhibited the enzyme, stabilized the enzyme to heat, and affected kinetic parameters. The isomerase was found to exhibit ionic strength-dependent hysteresis when enzyme, totally but reversibly inhibited by storage under conditions of high ionic strength of (NH4)2SO4, was transferred to a lower concentration of (NH4)2SO4. Alpha-Isopropylmalate isomerase was found to be sensitive to KCN and certain other chelators. The inactivation by KCN was prevented by high concentrations of (NH4)2SO4. These observations implicated a metal involvement but the nature of the metal was not revealed. The metal involvement and some of the other properties of alpha-isopropylmalate isomerase reveal a similarity to aconitase. The similarities in properties between the isomerase and aconitase are summarized. Studies of yeast alpha-isopropylmalate isomerase indicated that it is a single polypeptide of about Mr = 90,000."}
{"id": "PMID:6457", "title": "Differential reactivity of the two active site cysteine residues generated on reduction of pig heart lipoamide dehydrogenase.", "content": "Reduction of the active center disulfide bond in the flavoprotein pig heart lipoamide dehydrogenase generates two sulfur moieties which are chemically inequivalent in the 2-electron reduced form of the enzyme. Thus 1 cysteine residue is at least 13-fold more reactive than its partner toward iodoacetamide at pH 7.6. This selectivity was demonstrated by reaction of the 2-electron reduced enzyme with a low concentration of iodo[1-14C]acetamide under anaerobic conditions. The formation of a monolabeled derivative is accompanied by the reappearance of a spectrum of oxidized bound flavin, clearly different from that of the native enzyme. Alkylation of the remaining cysteine residues with iodo[12C]acetamide enabled the isolation of a tryptic version of the active center disulfide peptide. A single chymotryptic cleavage between the 2 alkylated cysteine residues generated a cationic and an anionic fragment containing 7% and 93% of the radioactivity of the purified tryptic peptide, respectively. The monolabeled derivative is catalytically inactive toward reduced or oxidized lipoamide, but is approximately 2-fold better as a transhydrogenase than the native protein using NADH and acetylpyridine adenine dinucleotide as substrates. Anaerobic titration with NADH leads to reduction of the flavin with concomitant formation of long wavelength absorption of low intensity. No intermediate reduced states were detected in this titration analogous to the red 2-electron form observed with the native enzyme. Similarly, intermediates during reduction of the enzyme by 1 eq of dithionite have not been detected.", "contents": "Differential reactivity of the two active site cysteine residues generated on reduction of pig heart lipoamide dehydrogenase. Reduction of the active center disulfide bond in the flavoprotein pig heart lipoamide dehydrogenase generates two sulfur moieties which are chemically inequivalent in the 2-electron reduced form of the enzyme. Thus 1 cysteine residue is at least 13-fold more reactive than its partner toward iodoacetamide at pH 7.6. This selectivity was demonstrated by reaction of the 2-electron reduced enzyme with a low concentration of iodo[1-14C]acetamide under anaerobic conditions. The formation of a monolabeled derivative is accompanied by the reappearance of a spectrum of oxidized bound flavin, clearly different from that of the native enzyme. Alkylation of the remaining cysteine residues with iodo[12C]acetamide enabled the isolation of a tryptic version of the active center disulfide peptide. A single chymotryptic cleavage between the 2 alkylated cysteine residues generated a cationic and an anionic fragment containing 7% and 93% of the radioactivity of the purified tryptic peptide, respectively. The monolabeled derivative is catalytically inactive toward reduced or oxidized lipoamide, but is approximately 2-fold better as a transhydrogenase than the native protein using NADH and acetylpyridine adenine dinucleotide as substrates. Anaerobic titration with NADH leads to reduction of the flavin with concomitant formation of long wavelength absorption of low intensity. No intermediate reduced states were detected in this titration analogous to the red 2-electron form observed with the native enzyme. Similarly, intermediates during reduction of the enzyme by 1 eq of dithionite have not been detected."}
{"id": "PMID:6458", "title": "Thyroxine-protein interactions. Interaction of thyroxine and triiodothyronine with human thyroxine-binding globulin.", "content": "The effect of temperature on the binding of thyroxine and triiodothyronine to thyroxine-binding globulin has been studied by equilibrium dialysis. Inclusion of ovalbumin in the dialysis mixture stabilized thyroxine-binding globulin against losses in binding activity which had been found to occur during equilibrium dialysis. Ovalbumin by itself bound the thyroid hormones very weakly and its binding could be neglected when analyzing the experimental results. At pH 7.4 and 37 degrees in 0.06 M potassium phosphate/0.7 mM EDTA buffer, thyroxine was bound to thyroxine-binding globulin at a single binding site with apparent association constants: at 5 degrees, K = 4.73 +/- 0.38 X 10(10) M-1; at 25 degrees, K = 1.55 +/- 0.17 X 10(10) M-1; and at 37 degrees, K = 9.08 +/- 0.62 X 10(9) M-1. Scatchard plots of the binding data for triiodothyronine indicated that the binding of this compound to thyroxine-binding globulin was more complex than that found for thyroxine. The data for triiodothyronine binding could be fitted by asuming the existence of two different classes of binding sites. At 5 degrees and pH 7.4 nonlinear regression analysis of the data yielded the values n1 = 1.04 +/- 0.10, K1 = 3.35 +/- 0.63 X 10(9) M-1 and n2 = 1.40 +/- 0.08, K2 = 0.69 +/- 0.20 X 10(8) M-1. At 25 degrees, the values for the binding constants were n1 = 1.04 +/- 0.38, K1 = 6.5 +/- 2.8 X 10(8) M-1 and n2 = 0.77 +/- 0.22, K2 = 0.43 +/- 0.62 X 10(8) M-1. At 37 degrees where less curvature was observed, the estimated binding constants were n1 = 1.02 +/- 0.06, K1 = 4.32 +/- 0.59 X 10(8) M-1 and n2K2 = 0.056 +/- 0.012 X 10(8) M-1. When n1 was fixed at 1, the resulting values obtained for the other three binding constants were at 25 degrees, K1 = 6.12 +/- 0.35 X 10(8) M-1, n2 = 0.72 +/- 0.18, K2 = 0.73 +/- 0.36 X 10(8) M-1; and at 37 degrees K1 = 3.80 +/- 0.22 X 10(8) M-1, n2 = 0.44 +/- 0.22, and K2 = 0.43 +/- 0.38 X 10(8) M-1. The thermodynamic values for thyroxine binding to thyroxine-binding globulin at 37 degrees and pH 7.4 were deltaG0 = -14.1 kcal/mole, deltaH0 = -8.96 kcal/mole, and deltaS0 = +16.7 cal degree-1 mole-1. For triiodothyronine at 37 degrees, the thermodynamic values for binding at the primary binding site were deltaG0 = -12.3 kcal/mole, deltaH0 = -11.9 kcal/mole, and deltaS0 = +1.4 cal degree-1 mole-1. Measurement of the pH dependence of binding indicated that both thyroxine and triiodothyronine were bound maximally in the region of physiological pH, pH 6.8 to 7.7.", "contents": "Thyroxine-protein interactions. Interaction of thyroxine and triiodothyronine with human thyroxine-binding globulin. The effect of temperature on the binding of thyroxine and triiodothyronine to thyroxine-binding globulin has been studied by equilibrium dialysis. Inclusion of ovalbumin in the dialysis mixture stabilized thyroxine-binding globulin against losses in binding activity which had been found to occur during equilibrium dialysis. Ovalbumin by itself bound the thyroid hormones very weakly and its binding could be neglected when analyzing the experimental results. At pH 7.4 and 37 degrees in 0.06 M potassium phosphate/0.7 mM EDTA buffer, thyroxine was bound to thyroxine-binding globulin at a single binding site with apparent association constants: at 5 degrees, K = 4.73 +/- 0.38 X 10(10) M-1; at 25 degrees, K = 1.55 +/- 0.17 X 10(10) M-1; and at 37 degrees, K = 9.08 +/- 0.62 X 10(9) M-1. Scatchard plots of the binding data for triiodothyronine indicated that the binding of this compound to thyroxine-binding globulin was more complex than that found for thyroxine. The data for triiodothyronine binding could be fitted by asuming the existence of two different classes of binding sites. At 5 degrees and pH 7.4 nonlinear regression analysis of the data yielded the values n1 = 1.04 +/- 0.10, K1 = 3.35 +/- 0.63 X 10(9) M-1 and n2 = 1.40 +/- 0.08, K2 = 0.69 +/- 0.20 X 10(8) M-1. At 25 degrees, the values for the binding constants were n1 = 1.04 +/- 0.38, K1 = 6.5 +/- 2.8 X 10(8) M-1 and n2 = 0.77 +/- 0.22, K2 = 0.43 +/- 0.62 X 10(8) M-1. At 37 degrees where less curvature was observed, the estimated binding constants were n1 = 1.02 +/- 0.06, K1 = 4.32 +/- 0.59 X 10(8) M-1 and n2K2 = 0.056 +/- 0.012 X 10(8) M-1. When n1 was fixed at 1, the resulting values obtained for the other three binding constants were at 25 degrees, K1 = 6.12 +/- 0.35 X 10(8) M-1, n2 = 0.72 +/- 0.18, K2 = 0.73 +/- 0.36 X 10(8) M-1; and at 37 degrees K1 = 3.80 +/- 0.22 X 10(8) M-1, n2 = 0.44 +/- 0.22, and K2 = 0.43 +/- 0.38 X 10(8) M-1. The thermodynamic values for thyroxine binding to thyroxine-binding globulin at 37 degrees and pH 7.4 were deltaG0 = -14.1 kcal/mole, deltaH0 = -8.96 kcal/mole, and deltaS0 = +16.7 cal degree-1 mole-1. For triiodothyronine at 37 degrees, the thermodynamic values for binding at the primary binding site were deltaG0 = -12.3 kcal/mole, deltaH0 = -11.9 kcal/mole, and deltaS0 = +1.4 cal degree-1 mole-1. Measurement of the pH dependence of binding indicated that both thyroxine and triiodothyronine were bound maximally in the region of physiological pH, pH 6.8 to 7.7."}
{"id": "PMID:6459", "title": "Purification and characterization of an endo-beta-galactosidase produced by Diplococcus pneumoniae.", "content": "An endo-beta-galactosidase acting on blood group A and B substances was found in the culture fluid of Diplococcus pneumoniae. The enzyme was purified 1000-fold, and its properties were studied in detail. The enzyme preparation, thus obtained, was practically free from various exoglycosidases, endo-beta-N-acetylglucosaminidase and proteases. The enzyme releases trisaccharides from blood group A and B active mucins purified from ovarian cyst fluid. The structures of the trisaccharides liberated from A and B active mucins were elucidated to be GalNAcalpha1 leads to 3(Fucalpha1 leads to 2)Gal and Galalpha1 leads to 3(Fucalpha1 leads to 2)Gal, respectively. The enzyme also hydrolyzes blood group A and B active oligosaccharides composed of type 2 chains, yielding the same products as in the case of ovarian cyst blood group substances. An H active mucin from ovarian cyst fluid, H active oligosaccharides, and A and B active oligosaccharides with type 1 chains were not hydrolyzed by the enzyme. Consequently, the enzyme catalyzes the following reaction, resulting in the degradation of blood type A and B determinants. (see article).", "contents": "Purification and characterization of an endo-beta-galactosidase produced by Diplococcus pneumoniae. An endo-beta-galactosidase acting on blood group A and B substances was found in the culture fluid of Diplococcus pneumoniae. The enzyme was purified 1000-fold, and its properties were studied in detail. The enzyme preparation, thus obtained, was practically free from various exoglycosidases, endo-beta-N-acetylglucosaminidase and proteases. The enzyme releases trisaccharides from blood group A and B active mucins purified from ovarian cyst fluid. The structures of the trisaccharides liberated from A and B active mucins were elucidated to be GalNAcalpha1 leads to 3(Fucalpha1 leads to 2)Gal and Galalpha1 leads to 3(Fucalpha1 leads to 2)Gal, respectively. The enzyme also hydrolyzes blood group A and B active oligosaccharides composed of type 2 chains, yielding the same products as in the case of ovarian cyst blood group substances. An H active mucin from ovarian cyst fluid, H active oligosaccharides, and A and B active oligosaccharides with type 1 chains were not hydrolyzed by the enzyme. Consequently, the enzyme catalyzes the following reaction, resulting in the degradation of blood type A and B determinants. (see article)."}
{"id": "PMID:6460", "title": "Cytochrome P-450 of bovine adrenal mitochondria. Ligand binding to two forms resolved by EPR spectroscopy.", "content": "The binding of cholest-5-ene-3beta,20alpha-diol (20alpha-hydroxycholesterol), 11-deoxycorticosterone, and aminoglutethimide to cytochrome P-450 in bovine adrenal mitochondria was measured by changes in optical spectra at room temperature and by EPR spectra at 14 K. The two methods provided nearly identical quantitation of these interactions with cytochrome P-450. Two distinct high spin forms of cytochrome P-450 were revealed by EPR spectra. The predominant high spin species (g = 8.2) was decreased by addition of 20alpha-hydroxycholesterol and elevated pH but was increased by addition of cholesterol. The minor high spin species (g = 8.1) was incrreased by addition of deoxycorticosterone but decreased by low concentrations of metyrapone. The two forms were evidently not in equilibrium and have been assigned to distinct forms of cytochrome P-450 involved in, respectively, cholesterol side chain cleavage (P-450scc) and steroid 11beta hydroxylation (P-450(11)beta). The high spin states are derived from complexes of these P-450 cytochromes with endogenous substrates, which are, respectively, cholesterol and deoxycorticoids. A high to low spin transition was observed when these complexes were turned over by initiating hydroxylation with malate. The contributions of cytochromes P-450(11)beta and P-450scc to the low spin spectrum were also resolved by similar means. At least 20% of P-450scc is in the low spin state while about 90% of P-450(11)beta is low spin in isolated beef adrenal mitochondria. Low spin complexes of cytochrome P-450scc with 20alpha-hydroxycholesterol and 3beta-hydroxypregn-5-ene-20-one (pregnenolone) gave distinct EPR spectra. Aminoglutethimide interacted with the total cytochrome P-450 content of the bovine adrenal mitochondria forming low spin complexes. Both optical and EPR data indicated binding to two forms of cytochrome P-450. These results suggest a detailed correlation between the spin state and absorbance changes seen at room temperature, illustrate that EPR allows the distinction of two principal forms of P-450, and suggest that there is no appreciable change in the spin state of either cytochrome between 14 K and 300 K.", "contents": "Cytochrome P-450 of bovine adrenal mitochondria. Ligand binding to two forms resolved by EPR spectroscopy. The binding of cholest-5-ene-3beta,20alpha-diol (20alpha-hydroxycholesterol), 11-deoxycorticosterone, and aminoglutethimide to cytochrome P-450 in bovine adrenal mitochondria was measured by changes in optical spectra at room temperature and by EPR spectra at 14 K. The two methods provided nearly identical quantitation of these interactions with cytochrome P-450. Two distinct high spin forms of cytochrome P-450 were revealed by EPR spectra. The predominant high spin species (g = 8.2) was decreased by addition of 20alpha-hydroxycholesterol and elevated pH but was increased by addition of cholesterol. The minor high spin species (g = 8.1) was incrreased by addition of deoxycorticosterone but decreased by low concentrations of metyrapone. The two forms were evidently not in equilibrium and have been assigned to distinct forms of cytochrome P-450 involved in, respectively, cholesterol side chain cleavage (P-450scc) and steroid 11beta hydroxylation (P-450(11)beta). The high spin states are derived from complexes of these P-450 cytochromes with endogenous substrates, which are, respectively, cholesterol and deoxycorticoids. A high to low spin transition was observed when these complexes were turned over by initiating hydroxylation with malate. The contributions of cytochromes P-450(11)beta and P-450scc to the low spin spectrum were also resolved by similar means. At least 20% of P-450scc is in the low spin state while about 90% of P-450(11)beta is low spin in isolated beef adrenal mitochondria. Low spin complexes of cytochrome P-450scc with 20alpha-hydroxycholesterol and 3beta-hydroxypregn-5-ene-20-one (pregnenolone) gave distinct EPR spectra. Aminoglutethimide interacted with the total cytochrome P-450 content of the bovine adrenal mitochondria forming low spin complexes. Both optical and EPR data indicated binding to two forms of cytochrome P-450. These results suggest a detailed correlation between the spin state and absorbance changes seen at room temperature, illustrate that EPR allows the distinction of two principal forms of P-450, and suggest that there is no appreciable change in the spin state of either cytochrome between 14 K and 300 K."}
{"id": "PMID:6461", "title": "The enzymic conversion of protoporphyrinogen IX to protoporphyrin IX in mammalian mitochondria.", "content": "Protoporphyrinogen oxidase, an enzyme which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX in yeast cells, has been found in several mammalian tissues. It has been extracted from rat liver mitochondria by sonication in the presence of salt and detergent and partially purified. The enzyme is similar in many respects to yeast protoporphyrinogen oxidase. Based on its behavior on Sephadex G-200 the molecular weight of the enzyme is approximately 35,000. Catalysis by protoporphyrinogen oxidase was specific for proteoporphyrinogen IX (apparent Km of 11 muM) and proceeded maximally at pH 8.6 to 8.7. The effect of temperature on enzyme activity plotted according to Arrhenius gave a value of E of 9,100 calories per mol. Enzyme activity was inhibited in the presence of high salt concentrations and temperatures above 45 degrees. Oxygen was essential for protoporphyrinogen oxidase activity and an alternative elevtron acceptor has not yet been found. No requirement for a metal or other cofactor could be demonstrated. The presence of monothiol groups was indicated; however, it is not known whether the thiol groups are involved directly in the binding of substrate to the enzyme.", "contents": "The enzymic conversion of protoporphyrinogen IX to protoporphyrin IX in mammalian mitochondria. Protoporphyrinogen oxidase, an enzyme which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX in yeast cells, has been found in several mammalian tissues. It has been extracted from rat liver mitochondria by sonication in the presence of salt and detergent and partially purified. The enzyme is similar in many respects to yeast protoporphyrinogen oxidase. Based on its behavior on Sephadex G-200 the molecular weight of the enzyme is approximately 35,000. Catalysis by protoporphyrinogen oxidase was specific for proteoporphyrinogen IX (apparent Km of 11 muM) and proceeded maximally at pH 8.6 to 8.7. The effect of temperature on enzyme activity plotted according to Arrhenius gave a value of E of 9,100 calories per mol. Enzyme activity was inhibited in the presence of high salt concentrations and temperatures above 45 degrees. Oxygen was essential for protoporphyrinogen oxidase activity and an alternative elevtron acceptor has not yet been found. No requirement for a metal or other cofactor could be demonstrated. The presence of monothiol groups was indicated; however, it is not known whether the thiol groups are involved directly in the binding of substrate to the enzyme."}
{"id": "PMID:6462", "title": "Conformational and thermodynamic properties of apo A-1 of human plasma high density lipoproteins.", "content": "Conformational changes of apo A-1, the principal apoprotein of human plasma high density lipoprotein, have been studied by differential scanning calorimetry and ultraviolet difference spectroscopy as a function of temperature, pH, concentration of apoprotein, and urea concentration. Calorimetry shows that apo A-1 (5 to 40 mg/ml, pH 9.2) undergoes a two-state, reversible denaturation (enthalpy = 64 +/- 8.9 kcal/mole), between 43--71 degrees (midpoint temperature, Tm = 54 degrees), associated with a rise in heat capacity (deltaCvd) of 2.4 +/- 0.5 kcal/mole/degrees C. Apo A-1 (0.2 to 0.4 mg/ml, pH 9.2) develops a negative difference spectrum between 42--70 degrees, with Tm = 53 degrees. The enthalpy (deltaH = 59 +/- 5.7 kcal/mole at Tm) and heat capacity change (2.7 +/- 0.9 kcal/mole/degrees C) in the spectroscopic experiments were not significantly different from the calorimetric values. Below pH 9 and above pH 11, the calorimetric Tm and deltaH of denaturation are decreased. In the pH range of reversible denaturation (6.5 to 11.8), delatH and Tm are linearly related, showing that the heat capacity change (ddeltaH/dT) associated with denaturation is independent of Tm. In urea solutions, the calorimetric Tm and deltaH of denaturation are decreased. At 25 degrees, apo A-1 develops a negative difference spectrum between 1.4 and 3 M urea. Fifty per cent of the spectral change occurs in 2.4 M urea, which corresponds to the urea concentration obtained by extrapolation of the calorimetric Tm to 25 degrees. In urea solution of less than 0.75 M there is hyperchromicity at 285 nm (delta epsilon = 264 in 0.75 M urea), indicating strong interaction of aromatic amino acid residues in the native molecule with the solvent. Spectrophotometric titration of apo A-1 shows that 6.6 of the 7 tyrosine groups of apo A-1 titrate at pH less than 11.9, with similar titration curves obtained in aqueous solutions and in 6 M urea. The free energy of stabilization (deltaG) of the native conformation of apo A-1 was estimated, (a) at 37 degrees, using the calorimetric deltaA and deltaCvd, and (b) at 25 degrees, by extrapolation of spectroscopic data to zero urea concentration. The values (deltaG (37 degrees) = 2.4 and deltaG (25 degrees) = 2.7 kcal/mole) are small compared to typical globular proteins, indicating that native apo A-1 has a loosely folded tertiary structure. The low values of deltaG reflect the high degree of exposure of hydrophobic areas in the native protein molecule. The loosely folded conformation of apo A-1 allows extensive binding of lipid, since this can involve both surface hydrophobic sites and hydrophobic areas exposed by a cooperative, low energy unfolding process.", "contents": "Conformational and thermodynamic properties of apo A-1 of human plasma high density lipoproteins. Conformational changes of apo A-1, the principal apoprotein of human plasma high density lipoprotein, have been studied by differential scanning calorimetry and ultraviolet difference spectroscopy as a function of temperature, pH, concentration of apoprotein, and urea concentration. Calorimetry shows that apo A-1 (5 to 40 mg/ml, pH 9.2) undergoes a two-state, reversible denaturation (enthalpy = 64 +/- 8.9 kcal/mole), between 43--71 degrees (midpoint temperature, Tm = 54 degrees), associated with a rise in heat capacity (deltaCvd) of 2.4 +/- 0.5 kcal/mole/degrees C. Apo A-1 (0.2 to 0.4 mg/ml, pH 9.2) develops a negative difference spectrum between 42--70 degrees, with Tm = 53 degrees. The enthalpy (deltaH = 59 +/- 5.7 kcal/mole at Tm) and heat capacity change (2.7 +/- 0.9 kcal/mole/degrees C) in the spectroscopic experiments were not significantly different from the calorimetric values. Below pH 9 and above pH 11, the calorimetric Tm and deltaH of denaturation are decreased. In the pH range of reversible denaturation (6.5 to 11.8), delatH and Tm are linearly related, showing that the heat capacity change (ddeltaH/dT) associated with denaturation is independent of Tm. In urea solutions, the calorimetric Tm and deltaH of denaturation are decreased. At 25 degrees, apo A-1 develops a negative difference spectrum between 1.4 and 3 M urea. Fifty per cent of the spectral change occurs in 2.4 M urea, which corresponds to the urea concentration obtained by extrapolation of the calorimetric Tm to 25 degrees. In urea solution of less than 0.75 M there is hyperchromicity at 285 nm (delta epsilon = 264 in 0.75 M urea), indicating strong interaction of aromatic amino acid residues in the native molecule with the solvent. Spectrophotometric titration of apo A-1 shows that 6.6 of the 7 tyrosine groups of apo A-1 titrate at pH less than 11.9, with similar titration curves obtained in aqueous solutions and in 6 M urea. The free energy of stabilization (deltaG) of the native conformation of apo A-1 was estimated, (a) at 37 degrees, using the calorimetric deltaA and deltaCvd, and (b) at 25 degrees, by extrapolation of spectroscopic data to zero urea concentration. The values (deltaG (37 degrees) = 2.4 and deltaG (25 degrees) = 2.7 kcal/mole) are small compared to typical globular proteins, indicating that native apo A-1 has a loosely folded tertiary structure. The low values of deltaG reflect the high degree of exposure of hydrophobic areas in the native protein molecule. The loosely folded conformation of apo A-1 allows extensive binding of lipid, since this can involve both surface hydrophobic sites and hydrophobic areas exposed by a cooperative, low energy unfolding process."}
{"id": "PMID:6463", "title": "Ketopantoate hydroxymethyltransferase. II. Physical, catalytic, and regulatory properties.", "content": "Some physical, catalytic, and regulatory properties of ketopantoate hydroxymethyltransferase (5,10-methylenetetrahydrofolate: alpha-ketoisovalerate hydroxymethyltranferase) from Escherichia coli are described. This enzyme catalyzes the reversible synthesis of ketopantoate (Reaction 1), an essential precursor of pantothenic acid. (1) HC(CH3)2COCOO- + 5,10-methylene tetrahydrofolate f in equilibrium r HOCH2C(CH3)2COCOO- + tetrahydrofolate  It has a molecular weight by sedimentation equilibrium of 255,000, a sedimentation coefficient (S20,w) of 11 S, a partial specific volume of 0.74 ml/g, an isoelectric point of 4.4, and an absorbance, (see article), of 0.85. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate and amino acid analyses give a subunit molecular weight of 27,000 and 25,700, respectively; both procedures indicate the presence of 10 identical subunits. The NH2-terminal sequence is Met-Tyr---. The enzyme is stable and active over a broad pH range, with an optimum from 7.0 to 7.6. It requires Mg2+ for activity; Mn2+, Co2+, Zn2+ are progressively less active. The enzyme is not inactivated by borohydride reduction in the presence of excess substrates, i.e. it is a Class II aldolase. Reaction 1f is partially inhibited by concentrations of formaldehyde (0.8 mM) and tetrahydrofolate (0.38 mM) below or near the Km values, apparent Km values are 0.18, 1.1 and 5.9 mM for tetrahydrofolate, alpha-ketoisovalerate, and formaldehyde, respectively. For Reaction 1r, apparent Km values are 0.16 and 0.18 mM, respectively, for ketopantoate and tetrahydrofolate, and the saturation curves for both substrates show positive cooperativity. Forward and reverse reactions occur at similar maximum velocities (Vmax approximately equal to 8 mumol of ketopantoate formed or decomposed per min per mg of enzyme at 37 degrees). Only 1-tetrahydrofolate is active in Reaction 1; d-tetrahydrofolate, folate, and methotrexate were neither active nor inhibitory. However, 1-tetrahydrofolate was effectively replaced with conjugates containing 1 to 6 additional glutamate residues; of these, tetrahydropterolpenta-, tetra-, and triglutamate were effective at lower concentrations than tetrahydrofolate itself; they were also the predominant conjugates of tetrahydrofolate present in E. coli. Alpha-Ketobutyrate, alpha-ketovalerate, and alpha-keto-beta-methylvalerate replaced alpha-ketoisovalerate as substrates; pyruvate was inactive as a substrate, but like isovalerate, 3-methyl-2-butanone and D- or L-valine, inhibited Reaction 1. the transferase has regulatory properties expected of an enzyme catalyzing the first committed step in a biosynthetic pathway. Pantoate (greater than or equal to 500 muM) and coenzyme A (above 1 mM) all inhibit; the Vmax is decreased, Km is increased, and the cooperativity for substrate (ketopantoate) is enhanced. Catalytic activity of the transferase is thus regulated by the products of the reaction path of which it is one component; transferase synthesis is not repressed by growth in the presence of pantothenate.", "contents": "Ketopantoate hydroxymethyltransferase. II. Physical, catalytic, and regulatory properties. Some physical, catalytic, and regulatory properties of ketopantoate hydroxymethyltransferase (5,10-methylenetetrahydrofolate: alpha-ketoisovalerate hydroxymethyltranferase) from Escherichia coli are described. This enzyme catalyzes the reversible synthesis of ketopantoate (Reaction 1), an essential precursor of pantothenic acid. (1) HC(CH3)2COCOO- + 5,10-methylene tetrahydrofolate f in equilibrium r HOCH2C(CH3)2COCOO- + tetrahydrofolate  It has a molecular weight by sedimentation equilibrium of 255,000, a sedimentation coefficient (S20,w) of 11 S, a partial specific volume of 0.74 ml/g, an isoelectric point of 4.4, and an absorbance, (see article), of 0.85. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate and amino acid analyses give a subunit molecular weight of 27,000 and 25,700, respectively; both procedures indicate the presence of 10 identical subunits. The NH2-terminal sequence is Met-Tyr---. The enzyme is stable and active over a broad pH range, with an optimum from 7.0 to 7.6. It requires Mg2+ for activity; Mn2+, Co2+, Zn2+ are progressively less active. The enzyme is not inactivated by borohydride reduction in the presence of excess substrates, i.e. it is a Class II aldolase. Reaction 1f is partially inhibited by concentrations of formaldehyde (0.8 mM) and tetrahydrofolate (0.38 mM) below or near the Km values, apparent Km values are 0.18, 1.1 and 5.9 mM for tetrahydrofolate, alpha-ketoisovalerate, and formaldehyde, respectively. For Reaction 1r, apparent Km values are 0.16 and 0.18 mM, respectively, for ketopantoate and tetrahydrofolate, and the saturation curves for both substrates show positive cooperativity. Forward and reverse reactions occur at similar maximum velocities (Vmax approximately equal to 8 mumol of ketopantoate formed or decomposed per min per mg of enzyme at 37 degrees). Only 1-tetrahydrofolate is active in Reaction 1; d-tetrahydrofolate, folate, and methotrexate were neither active nor inhibitory. However, 1-tetrahydrofolate was effectively replaced with conjugates containing 1 to 6 additional glutamate residues; of these, tetrahydropterolpenta-, tetra-, and triglutamate were effective at lower concentrations than tetrahydrofolate itself; they were also the predominant conjugates of tetrahydrofolate present in E. coli. Alpha-Ketobutyrate, alpha-ketovalerate, and alpha-keto-beta-methylvalerate replaced alpha-ketoisovalerate as substrates; pyruvate was inactive as a substrate, but like isovalerate, 3-methyl-2-butanone and D- or L-valine, inhibited Reaction 1. the transferase has regulatory properties expected of an enzyme catalyzing the first committed step in a biosynthetic pathway. Pantoate (greater than or equal to 500 muM) and coenzyme A (above 1 mM) all inhibit; the Vmax is decreased, Km is increased, and the cooperativity for substrate (ketopantoate) is enhanced. Catalytic activity of the transferase is thus regulated by the products of the reaction path of which it is one component; transferase synthesis is not repressed by growth in the presence of pantothenate."}
{"id": "PMID:6464", "title": "Re-evaluation of the kinetics of lactate dehydrogenase-catalyzed chain oxidation of nicotinamide adenine dinucleotide by superoxide radicals in the presence of ethylenediaminetetraacetate.", "content": "The chain oxidation of lactate dehydrogenase-bound NADH initiated by superoxide radicals and propagated by oxygen was studied with pulse radiolysis. The kinetic parameters were re-evaluated in a system with carefully purified reagents (water and other chemicals) and in the presence of EDTA. The rate constant for the oxidation of the enzyme-bound NADH by O2- is calculated from the observed pseudo-first order disappearance of NADH and the chain length (molecules of NADH oxidized per O2- anion generated in the pulse). It is (1.0 +/- 0.2) X 10(5) M-1 S-1, consistent within a 13-fold variation in lactate dehydrogenase. NADH complex concentration and with varying chain length up to 6.1. Based on experiments with varying pH values from 4.5 to 9.0, the rate constant for oxidation of enzyme-bound NADH by HO2 is estimated to be 2.0 X 10(6) M-1 S-1.", "contents": "Re-evaluation of the kinetics of lactate dehydrogenase-catalyzed chain oxidation of nicotinamide adenine dinucleotide by superoxide radicals in the presence of ethylenediaminetetraacetate. The chain oxidation of lactate dehydrogenase-bound NADH initiated by superoxide radicals and propagated by oxygen was studied with pulse radiolysis. The kinetic parameters were re-evaluated in a system with carefully purified reagents (water and other chemicals) and in the presence of EDTA. The rate constant for the oxidation of the enzyme-bound NADH by O2- is calculated from the observed pseudo-first order disappearance of NADH and the chain length (molecules of NADH oxidized per O2- anion generated in the pulse). It is (1.0 +/- 0.2) X 10(5) M-1 S-1, consistent within a 13-fold variation in lactate dehydrogenase. NADH complex concentration and with varying chain length up to 6.1. Based on experiments with varying pH values from 4.5 to 9.0, the rate constant for oxidation of enzyme-bound NADH by HO2 is estimated to be 2.0 X 10(6) M-1 S-1."}
{"id": "PMID:6465", "title": "Purification and characterization of the alpha-D-mannosidase of rat liver cytosol.", "content": "Three forms of alpha-D-mannosidase have previously been identified in rat liver, and each is localized in a different subcellular fraction: lysosomes, Golgi membranes, and cytosol. This communication reports the purification and characterization the cytosolic form. The enzyme was purified 12,000-fold in good yield to approximately 90% purity with the aid of the competitive inhibitor mannosylamine and dithioerythritol as stabilizers. The molecular weight of the enzyme is in the range of 372,000 to 490,000 depending on the method used. Since the subunit molecular weight is 110,000 by sodium dodecyl sulfate polyacrylamide electrophoresis, the enzyme is probably a tetramer. The pH optimum was shown to be between 5.5 and 5.9 (in the presence of 1 mM CoCl2) with the substrate p-nitrophenyl-alpha-D-mannoside. Normal Michaelis-Menten kinetics were observed with a Km of 0.14 mM. Mannosylamine was a competitive inhibitor with a Ki of 0.007 mM. The purified enzyme, stabilized by Co2+, Mn2+, and Fe2+ under some conditions, was unstable at low protein concentrations. Since an electrophoresed sample showed a positive periodic acid-Schiff stain, the enzyme may contain carbohydrate. The availability of purified cytosolic alpha-D-mannosidase should now make it possible to carry out substrate specificity, immunological, and structural studies which may shed light on the biological role of this enzyme.", "contents": "Purification and characterization of the alpha-D-mannosidase of rat liver cytosol. Three forms of alpha-D-mannosidase have previously been identified in rat liver, and each is localized in a different subcellular fraction: lysosomes, Golgi membranes, and cytosol. This communication reports the purification and characterization the cytosolic form. The enzyme was purified 12,000-fold in good yield to approximately 90% purity with the aid of the competitive inhibitor mannosylamine and dithioerythritol as stabilizers. The molecular weight of the enzyme is in the range of 372,000 to 490,000 depending on the method used. Since the subunit molecular weight is 110,000 by sodium dodecyl sulfate polyacrylamide electrophoresis, the enzyme is probably a tetramer. The pH optimum was shown to be between 5.5 and 5.9 (in the presence of 1 mM CoCl2) with the substrate p-nitrophenyl-alpha-D-mannoside. Normal Michaelis-Menten kinetics were observed with a Km of 0.14 mM. Mannosylamine was a competitive inhibitor with a Ki of 0.007 mM. The purified enzyme, stabilized by Co2+, Mn2+, and Fe2+ under some conditions, was unstable at low protein concentrations. Since an electrophoresed sample showed a positive periodic acid-Schiff stain, the enzyme may contain carbohydrate. The availability of purified cytosolic alpha-D-mannosidase should now make it possible to carry out substrate specificity, immunological, and structural studies which may shed light on the biological role of this enzyme."}
{"id": "PMID:6466", "title": "Effects of two ionizing groups on the active site of human carbonic anhydrase B.", "content": "Investigation of some pH-dependent properties of human erythrocyte carbonic anhydrase B indicate that the active site is influenced by at least two charged groups. The properties studied include the pH dependence of inhibition of native, monocarboxamidomethyl, and monocarboxymethyl enzymes by iodide ion and the pH dependence of the visible spectra of the cobalt derivatives of these enzymes. One ionizing group has a pKa of about 7.3 in the native enzyme, 8.2 in the carboxyamidomethyl enzyme, and 9.0 in the carboxymethyl enzyme. It has a major influence on activity and anion inhibition, and on the visible spectra of the cobalt enzymes. A second group has a pKa of about 6.1 in native and modified enzymes. When zinc is at the active site, the secondary group in its acidic form decreases the Ki for I-. With the carboxyamidomethyl and carboxymethyl enzymes, the Ki decreases by about an order of magnitude. However, if cobalt is substituted for zinc in the modified enzymes, this group does not influence the Ki for I- and the binding of I- does not influence the pKa of the spectral transitions caused by ionization of this secondary group. In the case of nonalkylated Co2+-enzyme, another ionizing group with a pK of about 6.2 prevents the binging of I- at low pH. These results show that the active site is altered when cobalt is substituted for zinc in carbonic anhydrase B.", "contents": "Effects of two ionizing groups on the active site of human carbonic anhydrase B. Investigation of some pH-dependent properties of human erythrocyte carbonic anhydrase B indicate that the active site is influenced by at least two charged groups. The properties studied include the pH dependence of inhibition of native, monocarboxamidomethyl, and monocarboxymethyl enzymes by iodide ion and the pH dependence of the visible spectra of the cobalt derivatives of these enzymes. One ionizing group has a pKa of about 7.3 in the native enzyme, 8.2 in the carboxyamidomethyl enzyme, and 9.0 in the carboxymethyl enzyme. It has a major influence on activity and anion inhibition, and on the visible spectra of the cobalt enzymes. A second group has a pKa of about 6.1 in native and modified enzymes. When zinc is at the active site, the secondary group in its acidic form decreases the Ki for I-. With the carboxyamidomethyl and carboxymethyl enzymes, the Ki decreases by about an order of magnitude. However, if cobalt is substituted for zinc in the modified enzymes, this group does not influence the Ki for I- and the binding of I- does not influence the pKa of the spectral transitions caused by ionization of this secondary group. In the case of nonalkylated Co2+-enzyme, another ionizing group with a pK of about 6.2 prevents the binging of I- at low pH. These results show that the active site is altered when cobalt is substituted for zinc in carbonic anhydrase B."}
{"id": "PMID:6467", "title": "Measurement of the oxidation-reduction potentials for two-electron and four-electron reduction of lipoamide dehydrogenase from pig heart.", "content": "The oxidation-reduction potential, E2, for the couple oxidized lipoamide dehydrogenase/2-electron reduced lipoamide dehydrogenase has been determined by measurement of equilibria of these enzyme species with lipoamide and dihydrolipoamide or with oxidized and reduced azine dyes. E2 is -0.280 V at pH 7, and deltaE2/deltapH is -0.06 V in the pH range 5.5 to 7.6. Values for E1, the oxidation-reduction potential for the couple 2-electron reduced enzyme/4-electron reduced enzyme, were obtained from measurements of the extent of dismutation of 2-electron reduced enzyme to form mixtures containing oxidized and 4-electron reduced enzyme. E1 is -0.346 V at pH 7, and deltaE1/deltapH is -0.06 V in the pH range 5.7 to 7.6. Spectra of oxidized enzyme and 4-electron reduced enzyme do not show variations with pH over this range, but the spectrum of the 2-electron reduced enzyme is pH-dependent, with the molar extinction at 530 nm changing from 3250 M-1 cm-1 at pH 8 to 2050 M-1 cm-1 at pH 5.2. The pH-dependent changes which are observed in the absorption properties of the 2-electron reduced enzyme are consistent with the disappearance of a charge transfer complex between an amino acid side chain and the oxidized flavin at the lower pH values, with the apparent pK of the side chain at pH 5. It has been suggested that the 530 nm absorbance of 2-electron reduced enzyme is due to a charge transfer complex between thiolate anion and oxidized flavin, and we propose that the thiolate anion is stabilized by interaction with a protonated base. The thermodynamic data predict that the amount of 4-electron reduced enzyme formed when the enzyme is reduced by excess NADH will be pH-dependent, with the greatest amounts seen at low pH values. These data support earlier evidence (Matthews, R.G., Wilkinson, K.D., Ballou, D,P., and Williams, C.H., Jr. (1976) in Flavins and Flavoproteins (Singer, T.P., ed) pp. 464-472; Elsevier Scientific Publishing Co., Amsterdam) that the role of NAD+ in the NADH-lipoamide reductase reaction catalyzed by lipoamide dehydrogenase is to prevent accumulation of inactive 4-electron reduced enzyme by simple reversal of the reduction of 2-electron reduced enzyme by NADH.", "contents": "Measurement of the oxidation-reduction potentials for two-electron and four-electron reduction of lipoamide dehydrogenase from pig heart. The oxidation-reduction potential, E2, for the couple oxidized lipoamide dehydrogenase/2-electron reduced lipoamide dehydrogenase has been determined by measurement of equilibria of these enzyme species with lipoamide and dihydrolipoamide or with oxidized and reduced azine dyes. E2 is -0.280 V at pH 7, and deltaE2/deltapH is -0.06 V in the pH range 5.5 to 7.6. Values for E1, the oxidation-reduction potential for the couple 2-electron reduced enzyme/4-electron reduced enzyme, were obtained from measurements of the extent of dismutation of 2-electron reduced enzyme to form mixtures containing oxidized and 4-electron reduced enzyme. E1 is -0.346 V at pH 7, and deltaE1/deltapH is -0.06 V in the pH range 5.7 to 7.6. Spectra of oxidized enzyme and 4-electron reduced enzyme do not show variations with pH over this range, but the spectrum of the 2-electron reduced enzyme is pH-dependent, with the molar extinction at 530 nm changing from 3250 M-1 cm-1 at pH 8 to 2050 M-1 cm-1 at pH 5.2. The pH-dependent changes which are observed in the absorption properties of the 2-electron reduced enzyme are consistent with the disappearance of a charge transfer complex between an amino acid side chain and the oxidized flavin at the lower pH values, with the apparent pK of the side chain at pH 5. It has been suggested that the 530 nm absorbance of 2-electron reduced enzyme is due to a charge transfer complex between thiolate anion and oxidized flavin, and we propose that the thiolate anion is stabilized by interaction with a protonated base. The thermodynamic data predict that the amount of 4-electron reduced enzyme formed when the enzyme is reduced by excess NADH will be pH-dependent, with the greatest amounts seen at low pH values. These data support earlier evidence (Matthews, R.G., Wilkinson, K.D., Ballou, D,P., and Williams, C.H., Jr. (1976) in Flavins and Flavoproteins (Singer, T.P., ed) pp. 464-472; Elsevier Scientific Publishing Co., Amsterdam) that the role of NAD+ in the NADH-lipoamide reductase reaction catalyzed by lipoamide dehydrogenase is to prevent accumulation of inactive 4-electron reduced enzyme by simple reversal of the reduction of 2-electron reduced enzyme by NADH."}
{"id": "PMID:6468", "title": "Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells.", "content": "Kinetic parameters of the interaction of the toxic lectins abrin and ricin with human erythrocytes and HeLa cells have been measured. The binding of 125I-labeled abrin and ricin to human erythrocytes and to HeLa cells at 37 degrees was maximal around pH 7, whereas at 0 degrees the binding was similar over a broad pH range. The binding occurred at similar rates at 0 degrees and 37 degrees with rate constants in the range 0.9 to 3.0 X 10(5) M-1 s-1. The dissociation was strongly temperature-dependent with rate constants in the range 3.4 to 45 X 10(-4) s-1 at 0 degrees and 3.9 to 18 X 10(-3) s-1 at 37 degrees. The presence of unlabeled lectins as well as lactose increased the rate of dissociation. The association constants measured at equilibrium or calculated from the rate constants were between 0.64 X 10(8) M-1 and 8.2 X 10(8) M-1 for abrus lectins, and between 8.0 X 10(6) M-1 and 4.2 X 10(8) M-1 for ricinus lectins. The association constants for the toxins were lower at 37 degrees than at 0 degrees. Isolated ricin B chain appeared to bind with similar affinity as intact ricin. The number of binding sites was estimated to be 2 to 3 X 10(6) per erythrocyte and 1 to 3 X 10(7) per HeLa cell. The binding sites of HeLa cells all displayed a uniform affinity towards abrin and ricin, both at 0 degrees and at 37 degrees. The same was the case with the binding sites of erythrocytes at 0 degrees. However, the data indicated that at 20 degrees erythrocytes possessed binding sites with two different affinities. Only a fraction of the cell-bound toxin appeared to be irreversibly bound and could not be removed by washing with 0.1 M lactose. The fraction of the total amount of bound toxin which became irreversibly bound to HeLa cells was for both toxins about 2 X 10(-3)/min at 37 degrees, whereas no toxin was irreversibly bound at 0 degrees. In the case of erythrocytes no toxin became irreversibly bound, either at 0 degrees or 37 degrees, indicating that the toxins are unable to penetrate into these cells.", "contents": "Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. Kinetic parameters of the interaction of the toxic lectins abrin and ricin with human erythrocytes and HeLa cells have been measured. The binding of 125I-labeled abrin and ricin to human erythrocytes and to HeLa cells at 37 degrees was maximal around pH 7, whereas at 0 degrees the binding was similar over a broad pH range. The binding occurred at similar rates at 0 degrees and 37 degrees with rate constants in the range 0.9 to 3.0 X 10(5) M-1 s-1. The dissociation was strongly temperature-dependent with rate constants in the range 3.4 to 45 X 10(-4) s-1 at 0 degrees and 3.9 to 18 X 10(-3) s-1 at 37 degrees. The presence of unlabeled lectins as well as lactose increased the rate of dissociation. The association constants measured at equilibrium or calculated from the rate constants were between 0.64 X 10(8) M-1 and 8.2 X 10(8) M-1 for abrus lectins, and between 8.0 X 10(6) M-1 and 4.2 X 10(8) M-1 for ricinus lectins. The association constants for the toxins were lower at 37 degrees than at 0 degrees. Isolated ricin B chain appeared to bind with similar affinity as intact ricin. The number of binding sites was estimated to be 2 to 3 X 10(6) per erythrocyte and 1 to 3 X 10(7) per HeLa cell. The binding sites of HeLa cells all displayed a uniform affinity towards abrin and ricin, both at 0 degrees and at 37 degrees. The same was the case with the binding sites of erythrocytes at 0 degrees. However, the data indicated that at 20 degrees erythrocytes possessed binding sites with two different affinities. Only a fraction of the cell-bound toxin appeared to be irreversibly bound and could not be removed by washing with 0.1 M lactose. The fraction of the total amount of bound toxin which became irreversibly bound to HeLa cells was for both toxins about 2 X 10(-3)/min at 37 degrees, whereas no toxin was irreversibly bound at 0 degrees. In the case of erythrocytes no toxin became irreversibly bound, either at 0 degrees or 37 degrees, indicating that the toxins are unable to penetrate into these cells."}
{"id": "PMID:6469", "title": "Sea urchin sperm guanylate cyclase. Purification and loss of cooperativity.", "content": "The Lubrol-dispersed guanylate cyclase from sea urchin sperm was purified and isolated essentially free of detergent by GTP affinity chromatography, DEAE-Sephadex chromatography, and gel filtration. After removal of the detergent, the enzyme remained in solution in the presence of 20% glycerol. The specific activity of the purified enzyme was about 12 mumol of guanosine 3':5'-monophosphate (cyclic GMP) formed - min-1 - mg of protein-1 at 30 degrees, an activity about 4600 times that of a soluble guanylate cyclase purified recently from Escherichia coli (Macchia V., Varrone, S., Weissbach, H., Miller, D.L., and Pastan, I. (1975) J. Biol. Chem. 250, 6214-6217). The cyclic GMP phosphodiesterase activity was negligible and adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase was not detectable in the purified preparation. Cyclic AMP formation from ATP occurred at a rate of 0.002% of that of guanylate cyclase. In the absence of phosphodiesterase or guanosine triphosphatase inhibitors, 100% of the added GTP was converted to cyclic GMP. The purified enzyme required Mn2+ for maximum activity, the relative rates in the presence of Mg2+ or Ca2+ being less than 0.6% of the rates with Mn2+. The purified enzyme displayed classical Michaelis-Menten kinetics with respect to MnGTP (apparent Km is approximately equal to 170 muM) in contrast to the positively cooperative kinetic behavior displayed by the unpurified, detergent-dispersed, or particulate guanylate cyclase. The molecular weight of the purified enzyme was approximately 182,000 as estimated on Bio-Gel A-0.5m columns equilibrated in the presence or absence of 0.1 M NaCl. The unpurified, detergent-dispersed enzyme also migrated with an apparent molecular weight of 182,000 on columns equilibrated with 0.5% Lubrol WX and 0.1 M NaCl, but it migrated as a large aggregate (molecular weight is greater than 5 X 10(5)) on columns equilibrated in the absence of either the detergent of NaCl. After gel filtration, the unpurified, dispersed enzyme still yielded positive cooperative kinetic patterns as a function of MnGTP. Na dodecyl-SO4 gel electrophoresis of the enzyme after the DEAE-Sephadex or the gel filtration steps resulted in two major protein bands with estimated molecular weights of 118,000 and 75,000. Whether or not these protein bands represent the subunit molecular weights of guanylate cyclase is unknown at present.", "contents": "Sea urchin sperm guanylate cyclase. Purification and loss of cooperativity. The Lubrol-dispersed guanylate cyclase from sea urchin sperm was purified and isolated essentially free of detergent by GTP affinity chromatography, DEAE-Sephadex chromatography, and gel filtration. After removal of the detergent, the enzyme remained in solution in the presence of 20% glycerol. The specific activity of the purified enzyme was about 12 mumol of guanosine 3':5'-monophosphate (cyclic GMP) formed - min-1 - mg of protein-1 at 30 degrees, an activity about 4600 times that of a soluble guanylate cyclase purified recently from Escherichia coli (Macchia V., Varrone, S., Weissbach, H., Miller, D.L., and Pastan, I. (1975) J. Biol. Chem. 250, 6214-6217). The cyclic GMP phosphodiesterase activity was negligible and adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase was not detectable in the purified preparation. Cyclic AMP formation from ATP occurred at a rate of 0.002% of that of guanylate cyclase. In the absence of phosphodiesterase or guanosine triphosphatase inhibitors, 100% of the added GTP was converted to cyclic GMP. The purified enzyme required Mn2+ for maximum activity, the relative rates in the presence of Mg2+ or Ca2+ being less than 0.6% of the rates with Mn2+. The purified enzyme displayed classical Michaelis-Menten kinetics with respect to MnGTP (apparent Km is approximately equal to 170 muM) in contrast to the positively cooperative kinetic behavior displayed by the unpurified, detergent-dispersed, or particulate guanylate cyclase. The molecular weight of the purified enzyme was approximately 182,000 as estimated on Bio-Gel A-0.5m columns equilibrated in the presence or absence of 0.1 M NaCl. The unpurified, detergent-dispersed enzyme also migrated with an apparent molecular weight of 182,000 on columns equilibrated with 0.5% Lubrol WX and 0.1 M NaCl, but it migrated as a large aggregate (molecular weight is greater than 5 X 10(5)) on columns equilibrated in the absence of either the detergent of NaCl. After gel filtration, the unpurified, dispersed enzyme still yielded positive cooperative kinetic patterns as a function of MnGTP. Na dodecyl-SO4 gel electrophoresis of the enzyme after the DEAE-Sephadex or the gel filtration steps resulted in two major protein bands with estimated molecular weights of 118,000 and 75,000. Whether or not these protein bands represent the subunit molecular weights of guanylate cyclase is unknown at present."}
{"id": "PMID:6470", "title": "Biochemical characterization of mutant forms of DNA polymerase I from Escherichia coli. I. The polA12 mutation.", "content": "DNA polymerase I has been purified to greater than 90% homogeneity from a strain of Escherichia coli K12 that bears the temperature-sensitive DNA polymerase I mutatation, polA12. The mutant enzyme has a reduced electrophoretic mobility and sedimentation rate. It is abnormally thermolabile and is rapidly inactivated at low salt concentrations. Its polymerase and 5' leads to 3' exonuclease activities are not grossly defective at 30 degrees, yet its capacity to promote the concerted 5' leads to 3' polymerization and the 5' leads to 3' exonucleolytic hydrolysis of nucleotides at a nick (\"nick translation\") is decreased 10-fold. These effects are probably the result of a significant alteration in the tertiary structure of the enzyme.", "contents": "Biochemical characterization of mutant forms of DNA polymerase I from Escherichia coli. I. The polA12 mutation. DNA polymerase I has been purified to greater than 90% homogeneity from a strain of Escherichia coli K12 that bears the temperature-sensitive DNA polymerase I mutatation, polA12. The mutant enzyme has a reduced electrophoretic mobility and sedimentation rate. It is abnormally thermolabile and is rapidly inactivated at low salt concentrations. Its polymerase and 5' leads to 3' exonuclease activities are not grossly defective at 30 degrees, yet its capacity to promote the concerted 5' leads to 3' polymerization and the 5' leads to 3' exonucleolytic hydrolysis of nucleotides at a nick (\"nick translation\") is decreased 10-fold. These effects are probably the result of a significant alteration in the tertiary structure of the enzyme."}
{"id": "PMID:6471", "title": "Purification of plasma membrane penicillinase from Bacillus licheniformis 749/C and comparison with exoenzyme.", "content": "The membrane penicillinase of Bacillus licheniformis 749/C has been demonstrated to be a phospholipoprotein. The homogeneous enzyme gives a positive reaction for phosphorous and for unsaturated fatty acids, has a molecular weight of 33,000 in contrast to 29,000 for the exoenzyme, and contains 8 to 9 additional residues of aspartate or asparagine, 4 to 5 of serine, 7 of glutamate or glutamine, and 4 to 5 of glycine per mole. The COOH-terminal sequence of both membrane and exoenzymes is -Met-Asn-Gln-Lys-COOH; hence the extra peptide portion present in the membrane enzyme is not attached to the COOH-terminus of the exoenzyme. Procedures which readily detected the lysine residue at the NH2 terminus of the exoenzyme did not yield a positive test with the membrane form. The NH2 terminus of the membrane enzyme may be blocked by or linked to the phospholipid. A procedure for the preparation of membrane penicillinase on a large scale and an improved method for purification of the exoenzyme have been developed.", "contents": "Purification of plasma membrane penicillinase from Bacillus licheniformis 749/C and comparison with exoenzyme. The membrane penicillinase of Bacillus licheniformis 749/C has been demonstrated to be a phospholipoprotein. The homogeneous enzyme gives a positive reaction for phosphorous and for unsaturated fatty acids, has a molecular weight of 33,000 in contrast to 29,000 for the exoenzyme, and contains 8 to 9 additional residues of aspartate or asparagine, 4 to 5 of serine, 7 of glutamate or glutamine, and 4 to 5 of glycine per mole. The COOH-terminal sequence of both membrane and exoenzymes is -Met-Asn-Gln-Lys-COOH; hence the extra peptide portion present in the membrane enzyme is not attached to the COOH-terminus of the exoenzyme. Procedures which readily detected the lysine residue at the NH2 terminus of the exoenzyme did not yield a positive test with the membrane form. The NH2 terminus of the membrane enzyme may be blocked by or linked to the phospholipid. A procedure for the preparation of membrane penicillinase on a large scale and an improved method for purification of the exoenzyme have been developed."}
{"id": "PMID:6473", "title": "Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Temperature dependence of oxygen binding and pH dependence of subunit dissociation.", "content": "The temperature dependence of the oxygen equilibrium of tadpole hemoglobin has been determined between 0 degrees and 32 degrees for the unfractionated but phosphate-free lysate and between 12 degrees and 32 degrees for each of the four isolated components between pH 6 and 10 in 0.05 M cacodylate, Tris, or glycine buffers containing 0.1 M NaCl and 1 mM EDTA. Under these conditions the Bohr effect (defined as deltalog p50/deltapH) of the unfractionated lysate is positive at low temperatures between pH 6 and 8.5 and is negative above pH 8.5 to 8.8 at any temperature. As the temperature rises the Bohr effect below pH 8.5 changes greatly. In the interval pH 7.0 to 7.5, the magnitude of the Bohr effect decreases from + 0.28 at 0 degrees to zero at about 24 degrees and becomes negative, as in mammalian hemoglobins, above this temperature. Measurements with the isolated components show that the temperature dependence of oxygen binding for Components I and II and for Components III and IV is very similar. For both sets of components the apparent overall enthalpy of oxygenation at pH 7.5 is about -16.4 kcal/mol and -12.6 kcal/mol at pH 9.5. The measured enthalpies include contributions from the active Bohr groups, the buffer ions themselves, the hemoglobin groups contributing buffering, and any pH-dependent, oxygenation-dependent binding of ions such as chloride by the hemoglobin. The apportioning of the total enthalpy among these various processes remains to be determined. Between pH 8 and 10.5 tadpole oxyhemoglobin undergoes a pH-dependent dissociation from tetramer to dimer. The pH dependence of the apparent tetramer-dimer dissociation constant indicates that at pH 9.5 the dissociation of each tetramer is accompanied by the release of approximately 2 protons. In this pH range the oxygen equilibrium measurements indicate that about 0.5 proton is released for each oxygen molecule bound. The results are consistent with the conclusion that one acid group per alphabeta dimer changes its pK from about 10 to 8 or below upon dissociation of the tetramer.", "contents": "Hemoglobins of the tadpole of the bullfrog, Rana catesbeiana. Temperature dependence of oxygen binding and pH dependence of subunit dissociation. The temperature dependence of the oxygen equilibrium of tadpole hemoglobin has been determined between 0 degrees and 32 degrees for the unfractionated but phosphate-free lysate and between 12 degrees and 32 degrees for each of the four isolated components between pH 6 and 10 in 0.05 M cacodylate, Tris, or glycine buffers containing 0.1 M NaCl and 1 mM EDTA. Under these conditions the Bohr effect (defined as deltalog p50/deltapH) of the unfractionated lysate is positive at low temperatures between pH 6 and 8.5 and is negative above pH 8.5 to 8.8 at any temperature. As the temperature rises the Bohr effect below pH 8.5 changes greatly. In the interval pH 7.0 to 7.5, the magnitude of the Bohr effect decreases from + 0.28 at 0 degrees to zero at about 24 degrees and becomes negative, as in mammalian hemoglobins, above this temperature. Measurements with the isolated components show that the temperature dependence of oxygen binding for Components I and II and for Components III and IV is very similar. For both sets of components the apparent overall enthalpy of oxygenation at pH 7.5 is about -16.4 kcal/mol and -12.6 kcal/mol at pH 9.5. The measured enthalpies include contributions from the active Bohr groups, the buffer ions themselves, the hemoglobin groups contributing buffering, and any pH-dependent, oxygenation-dependent binding of ions such as chloride by the hemoglobin. The apportioning of the total enthalpy among these various processes remains to be determined. Between pH 8 and 10.5 tadpole oxyhemoglobin undergoes a pH-dependent dissociation from tetramer to dimer. The pH dependence of the apparent tetramer-dimer dissociation constant indicates that at pH 9.5 the dissociation of each tetramer is accompanied by the release of approximately 2 protons. In this pH range the oxygen equilibrium measurements indicate that about 0.5 proton is released for each oxygen molecule bound. The results are consistent with the conclusion that one acid group per alphabeta dimer changes its pK from about 10 to 8 or below upon dissociation of the tetramer."}
{"id": "PMID:6474", "title": "Dissociation of CO from carboxyhemoglobin.", "content": "The reaction between carboxyhemoglobin and reduced microperoxidase (MP): Hb4(CO)4 + 4MP=Hb4 + 4MPCO, recently reported by us, has been further studied. By generating species Hb4(CO), Hb4(CO)2, and Hb(CO)3 in the stopped flow cuvette by the reaction of dithionite with the species of the general formula Hb4(O2)x(CO)y(x + y=4) in the presence of microperoxidase it has been possible to determine the stepwise CO dissociation rate constants l4, l3, l2, and l1. The overall CO dissociation rate constant l, which is the same in this system as l4, is not affected by 2,3-diphosphoglyceric acid. The activation energy of the reaction is 21,400 cal in 15-25 degrees range. The ratio deltal/deltapH is approximately 3 in 6.5 to 7.5 pH range. The kinetic data indicate that, compared to HbO2, the contribution to the cooperativity of the dissociation rate constants of carboxyhemoglobin is greatly reduced. The ligand-dependent differences in the reactions of Hb with CO, O2, and NO suggest that in the combination reactions the ligand plays an active role in the rate-limiting step.", "contents": "Dissociation of CO from carboxyhemoglobin. The reaction between carboxyhemoglobin and reduced microperoxidase (MP): Hb4(CO)4 + 4MP=Hb4 + 4MPCO, recently reported by us, has been further studied. By generating species Hb4(CO), Hb4(CO)2, and Hb(CO)3 in the stopped flow cuvette by the reaction of dithionite with the species of the general formula Hb4(O2)x(CO)y(x + y=4) in the presence of microperoxidase it has been possible to determine the stepwise CO dissociation rate constants l4, l3, l2, and l1. The overall CO dissociation rate constant l, which is the same in this system as l4, is not affected by 2,3-diphosphoglyceric acid. The activation energy of the reaction is 21,400 cal in 15-25 degrees range. The ratio deltal/deltapH is approximately 3 in 6.5 to 7.5 pH range. The kinetic data indicate that, compared to HbO2, the contribution to the cooperativity of the dissociation rate constants of carboxyhemoglobin is greatly reduced. The ligand-dependent differences in the reactions of Hb with CO, O2, and NO suggest that in the combination reactions the ligand plays an active role in the rate-limiting step."}
{"id": "PMID:6475", "title": "Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH.", "content": "Anaerobic reduction of the flavoprotein adrenodoxin reductase with NADPH yields a spectrum with long wavelength absorbance, 750 nm and higher. No EPR signal is observed. This spectrum is produced by titration of oxidized adrenodoxin reductase with NADPH, or of dithionite-reduced adrenodoxin reductase with NADP+. Both titrations yield a sharp endpoint at 1 NADP(H) added per flavin. Reduction with other reductants, including dithionite, excess NADH, and catalytic NADP+ with an NADPH generating system, yields a typical fully reduced flavin spectrum, without long wavelength absorbance. The species formed on NADPH reduction appears to be a two-electron-containing complex, with a low dissociation constant, between reduced adrenodoxin reductase and NADP+, designated ARH2-NADP+. Titration of dithionite-reduced adrenodoxin reductase with NADPH also produces a distinctive spectrum, with a sharp endpoint at 1 NADPH added per reduced flavin, indicating formation of a four-electron-containing complex between reduced adrenodoxin reductase and NADPH. Titration of adrenodoxin reductase with NADH, instead of NADPH, provides a curved titration plot rather than the sharp break seen with NADPH, and permits calculation of a potential for the AR/ARH2 couple of -0.291 V, close to that of NAD(P)H (-0.316 V). Oxidized adrenodoxin reductase binds NADP+ much more weakly (Kdiss=1.4 X 10(-5) M) than does reduced adrenodoxin reductase, with a single binding site. The preferential binding of NADP+ to reduced enzyme permits prediction of a more positive oxidation-reduction potential of the flavoprotein in the presence of NADP+; a change of about + 0.1 V has been demonstrated by titration with safranine T. From this alteration in potential, a Kdiss of 1.0 X 10(-8) M for binding of NADP+ to reduced adrenodoxin reductase is calculated. It is concluded that the strong binding of NADP+ to reduced adrenodoxin reductase provides the thermodynamic driving force for formation of a fully reduced flavoprotein form under conditions wherein incomplete reduction would otherwise be expected. Stopped flow studies demonstrate that reduction of adrenodoxin reductase by equimolar NADPH to form the ARH2-NADP+ complex is first order (k=28 s-1). When a large excess of NADPH is used, a second apparently first order process is observed (k=4.25 s-1), which is interpreted as replacement of NADPH for NADP+ in the ARH2-NADP+ complex. Comparison of these rate constants to catalytic flavin turnover numbers for reduction of various oxidants by NADPH, suggests an ordered sequential mechanism in which reduction of oxidant is accomplished by the ARH2-NADP+ complex, followed by dissociation of NADP+. The absolute dependence of NADPH-cytochrome c reduction on both adrenodoxin reductase and adrenodoxin is confirmed...", "contents": "Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH. Anaerobic reduction of the flavoprotein adrenodoxin reductase with NADPH yields a spectrum with long wavelength absorbance, 750 nm and higher. No EPR signal is observed. This spectrum is produced by titration of oxidized adrenodoxin reductase with NADPH, or of dithionite-reduced adrenodoxin reductase with NADP+. Both titrations yield a sharp endpoint at 1 NADP(H) added per flavin. Reduction with other reductants, including dithionite, excess NADH, and catalytic NADP+ with an NADPH generating system, yields a typical fully reduced flavin spectrum, without long wavelength absorbance. The species formed on NADPH reduction appears to be a two-electron-containing complex, with a low dissociation constant, between reduced adrenodoxin reductase and NADP+, designated ARH2-NADP+. Titration of dithionite-reduced adrenodoxin reductase with NADPH also produces a distinctive spectrum, with a sharp endpoint at 1 NADPH added per reduced flavin, indicating formation of a four-electron-containing complex between reduced adrenodoxin reductase and NADPH. Titration of adrenodoxin reductase with NADH, instead of NADPH, provides a curved titration plot rather than the sharp break seen with NADPH, and permits calculation of a potential for the AR/ARH2 couple of -0.291 V, close to that of NAD(P)H (-0.316 V). Oxidized adrenodoxin reductase binds NADP+ much more weakly (Kdiss=1.4 X 10(-5) M) than does reduced adrenodoxin reductase, with a single binding site. The preferential binding of NADP+ to reduced enzyme permits prediction of a more positive oxidation-reduction potential of the flavoprotein in the presence of NADP+; a change of about + 0.1 V has been demonstrated by titration with safranine T. From this alteration in potential, a Kdiss of 1.0 X 10(-8) M for binding of NADP+ to reduced adrenodoxin reductase is calculated. It is concluded that the strong binding of NADP+ to reduced adrenodoxin reductase provides the thermodynamic driving force for formation of a fully reduced flavoprotein form under conditions wherein incomplete reduction would otherwise be expected. Stopped flow studies demonstrate that reduction of adrenodoxin reductase by equimolar NADPH to form the ARH2-NADP+ complex is first order (k=28 s-1). When a large excess of NADPH is used, a second apparently first order process is observed (k=4.25 s-1), which is interpreted as replacement of NADPH for NADP+ in the ARH2-NADP+ complex. Comparison of these rate constants to catalytic flavin turnover numbers for reduction of various oxidants by NADPH, suggests an ordered sequential mechanism in which reduction of oxidant is accomplished by the ARH2-NADP+ complex, followed by dissociation of NADP+. The absolute dependence of NADPH-cytochrome c reduction on both adrenodoxin reductase and adrenodoxin is confirmed..."}
{"id": "PMID:6476", "title": "A transition state analog of lysozyme catalysis prepared from the bacterial cell wall tetrasaccharide.", "content": "Treatment of the cell wall tetrasaccharide GlcNAcbeta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-MurNAc with alkali resulted in the formation of the unsaturated tetrasaccharide GlcNAc-beta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-delta2,3-2-acetamido-2-deoxy-D-glucoseen. The same compound was also formed by transglycosylation upon incubation of the unmodified tetrasaccharide with the unsaturated disaccharide GlcNAc-beta(1 leads to 4)-delta2,3-2-acetamido-2-deoxy-D-glucoseen (Tipper, D. J. (1968) Biochemistry 7, 1441-1449) and hen egg white lysozyme. The unsaturated tetrasaccharide was further characterized by paper electrophoresis, amino sugar analysis, and NMR. From NMR analysis it is concluded that the delta2,3-2-acetamido-2-deoxy-D-glucoseen at the reducing end of the unsaturated tetrasaccharide has a half-chair conformation. This conformation is similar to the one proposed for the sugar at subsite D in the lysozyme-substrate complex in the transition state. Addition of the unsaturated tetrasaccharide to a solution of hen egg white lysozyme quenched the fluorescence of the enzyme and shifted the fluorescence maximum to the blue, similar to the effect produced by the parent compound. The association constant of the unsaturated tetrasaccharide and lysozyme was measured at pH 6.0 and 24 degrees by spectrofluorimetry and microcalorimetry and found to be 1.45 X 10(5) M-1 and 2.5 X 10(5) M-1, respectively. The average value is 100 times higher than that found for the binding of unmodified tetrasaccharide to the enzyme under the same conditions. The unsaturated tetrasaccharide proved to be a better inhibitor of the lysis of Micrococcus luteus cells than the parent compound by a factor of 35. These results support the hypothesis that the active site of the enzyme is constructed so as to bind the transition state for the reaction it catalyzes more firmly than the substrate itself.", "contents": "A transition state analog of lysozyme catalysis prepared from the bacterial cell wall tetrasaccharide. Treatment of the cell wall tetrasaccharide GlcNAcbeta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-MurNAc with alkali resulted in the formation of the unsaturated tetrasaccharide GlcNAc-beta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-delta2,3-2-acetamido-2-deoxy-D-glucoseen. The same compound was also formed by transglycosylation upon incubation of the unmodified tetrasaccharide with the unsaturated disaccharide GlcNAc-beta(1 leads to 4)-delta2,3-2-acetamido-2-deoxy-D-glucoseen (Tipper, D. J. (1968) Biochemistry 7, 1441-1449) and hen egg white lysozyme. The unsaturated tetrasaccharide was further characterized by paper electrophoresis, amino sugar analysis, and NMR. From NMR analysis it is concluded that the delta2,3-2-acetamido-2-deoxy-D-glucoseen at the reducing end of the unsaturated tetrasaccharide has a half-chair conformation. This conformation is similar to the one proposed for the sugar at subsite D in the lysozyme-substrate complex in the transition state. Addition of the unsaturated tetrasaccharide to a solution of hen egg white lysozyme quenched the fluorescence of the enzyme and shifted the fluorescence maximum to the blue, similar to the effect produced by the parent compound. The association constant of the unsaturated tetrasaccharide and lysozyme was measured at pH 6.0 and 24 degrees by spectrofluorimetry and microcalorimetry and found to be 1.45 X 10(5) M-1 and 2.5 X 10(5) M-1, respectively. The average value is 100 times higher than that found for the binding of unmodified tetrasaccharide to the enzyme under the same conditions. The unsaturated tetrasaccharide proved to be a better inhibitor of the lysis of Micrococcus luteus cells than the parent compound by a factor of 35. These results support the hypothesis that the active site of the enzyme is constructed so as to bind the transition state for the reaction it catalyzes more firmly than the substrate itself."}
{"id": "PMID:6477", "title": "The study of 1-electron equivalent oxidation-reduction reactions by fast pulse generation of reagents. Cytochrome c/ferri-ferrocyanide system.", "content": "The method of pulse radiolysis was used to generate reagents in situ in times (500 ns to 1.5 mus) short compared with the rates of the observed biochemical processes. This \"instant\" mixing technique is compared with rapid stopped flow measurements (limited in rates and concentrations) and T-jump measurements (limited to relaxation in the neighborhood of equilibrium) for the ferro-ferricytochrome c (C(II)-C(III))/ferro-ferricyanide (FCN(II)-FCN(III)) system. The reagents generated in situ were C(II) or FCN(III). Kinetically indistinguishable binding sites exist on C(II) and C(III) for hexacyanide anions. Reductive electron transfer to the protein proceeds within the FCN(II)-C(III) complex, with a rate of 400 s-1. The binding of FCN(II) on C(II) slows down the oxidation of C(II) by FCN(III). The sites of interaction on C(II) or C(III) with FCN(III) show effective charges of approximately +2. The association constant per binding site derived from the kinetics of electron transfer is greater than or equal to 10(4) M-1 for FCN(II)-C(II) and less than or equal to 10(4) M-1 for FCN(III)-C(III). Specific clusters of amino acids in the model of cytochrome C are suggested as binding sites. The oxidation-reduction reactions of FCN appear to involve electron equivalent transfer to and from such somewhat remote binding sites on the protein. Anions such as phosphate or sulphate also bind to these, less strongly than hexacyanides. In the presence of perchlorate the kinetics show the resolution of the pK=9.3 of C(III) into two parts: (a) optical changes at 695 nm due to ligand interchange on the heme-iron, unaffected by perchlorate and (b), a kinetic change leading to biphasic oxidation of C(II), with pK=7.4. This is attributed to the effect of perchlorate on water structure in the close environment of the binding sites. The high rate of oxidation of relaxed C(II) by FCN(III), (2 X 10(8) M-1 S-1 at mu=0) is not in agreement with an outer sphere Marcus mechanism. Nonrelaxed C(II) having a structure closer to C(III) transfers electron to FCN(III) even faster (k=3 X 10(9) M-1 S-1 at mu=0).", "contents": "The study of 1-electron equivalent oxidation-reduction reactions by fast pulse generation of reagents. Cytochrome c/ferri-ferrocyanide system. The method of pulse radiolysis was used to generate reagents in situ in times (500 ns to 1.5 mus) short compared with the rates of the observed biochemical processes. This \"instant\" mixing technique is compared with rapid stopped flow measurements (limited in rates and concentrations) and T-jump measurements (limited to relaxation in the neighborhood of equilibrium) for the ferro-ferricytochrome c (C(II)-C(III))/ferro-ferricyanide (FCN(II)-FCN(III)) system. The reagents generated in situ were C(II) or FCN(III). Kinetically indistinguishable binding sites exist on C(II) and C(III) for hexacyanide anions. Reductive electron transfer to the protein proceeds within the FCN(II)-C(III) complex, with a rate of 400 s-1. The binding of FCN(II) on C(II) slows down the oxidation of C(II) by FCN(III). The sites of interaction on C(II) or C(III) with FCN(III) show effective charges of approximately +2. The association constant per binding site derived from the kinetics of electron transfer is greater than or equal to 10(4) M-1 for FCN(II)-C(II) and less than or equal to 10(4) M-1 for FCN(III)-C(III). Specific clusters of amino acids in the model of cytochrome C are suggested as binding sites. The oxidation-reduction reactions of FCN appear to involve electron equivalent transfer to and from such somewhat remote binding sites on the protein. Anions such as phosphate or sulphate also bind to these, less strongly than hexacyanides. In the presence of perchlorate the kinetics show the resolution of the pK=9.3 of C(III) into two parts: (a) optical changes at 695 nm due to ligand interchange on the heme-iron, unaffected by perchlorate and (b), a kinetic change leading to biphasic oxidation of C(II), with pK=7.4. This is attributed to the effect of perchlorate on water structure in the close environment of the binding sites. The high rate of oxidation of relaxed C(II) by FCN(III), (2 X 10(8) M-1 S-1 at mu=0) is not in agreement with an outer sphere Marcus mechanism. Nonrelaxed C(II) having a structure closer to C(III) transfers electron to FCN(III) even faster (k=3 X 10(9) M-1 S-1 at mu=0)."}
{"id": "PMID:6478", "title": "beta-Mannosidase from the mushroom Polyporus sulfureus.", "content": "beta-D-Mannosidase (EC 3.2.1.25), a useful tool for the structural studies of heterosaccharide chains, has been isolated in a highly purified form from the fruiting bodies of the mushroom Polyporus sulfureus. This mushroom is unique among reported sources of this enzyme in that it has the advantage of being almost free of alpha-mannosidase activity. The purification procedure involves ammonium sulfate fractionation followed by Sephadex G-100 filtration and chromatography on columns of DEAE-cellulose and hydroxylapatite. The final enzyme preparation gives essentially a single band on disc gel electrophoresis. The purified enzyme liberates the beta-D-mannopyranosyl unit from various natural substrates such as the core glycopeptide, Man(GlcNAc)2-Asn isolated from ovalbumin, from Taka-amylase A, and from human alpha1-acid glycoprotein. It also hydrolyzes (Man)2-GlcNAc from the urine of an alpha-mannosidosis patient, 1,4-D-mannobiose and mannotriose isolated from ivory nut mannan, 4-O-beta-D-mannopyranosyl-L-rhamnose, 6-O-beta-D-mannopyranosyl-D-galactose and 4-O-beta-D-mannopyranosyl-N-acetylglucosamine. The molecular weight of this enzyme is estimated to be about 64,000 by gel filtration. For p-nitrophenyl-beta-D-mannopyranoside, the pH optimum is between 2.4 and 3.4 and the Km is 1.6 mM.", "contents": "beta-Mannosidase from the mushroom Polyporus sulfureus. beta-D-Mannosidase (EC 3.2.1.25), a useful tool for the structural studies of heterosaccharide chains, has been isolated in a highly purified form from the fruiting bodies of the mushroom Polyporus sulfureus. This mushroom is unique among reported sources of this enzyme in that it has the advantage of being almost free of alpha-mannosidase activity. The purification procedure involves ammonium sulfate fractionation followed by Sephadex G-100 filtration and chromatography on columns of DEAE-cellulose and hydroxylapatite. The final enzyme preparation gives essentially a single band on disc gel electrophoresis. The purified enzyme liberates the beta-D-mannopyranosyl unit from various natural substrates such as the core glycopeptide, Man(GlcNAc)2-Asn isolated from ovalbumin, from Taka-amylase A, and from human alpha1-acid glycoprotein. It also hydrolyzes (Man)2-GlcNAc from the urine of an alpha-mannosidosis patient, 1,4-D-mannobiose and mannotriose isolated from ivory nut mannan, 4-O-beta-D-mannopyranosyl-L-rhamnose, 6-O-beta-D-mannopyranosyl-D-galactose and 4-O-beta-D-mannopyranosyl-N-acetylglucosamine. The molecular weight of this enzyme is estimated to be about 64,000 by gel filtration. For p-nitrophenyl-beta-D-mannopyranoside, the pH optimum is between 2.4 and 3.4 and the Km is 1.6 mM."}
{"id": "PMID:6479", "title": "The carbamate reaction of glycylglycine, plasma, and tissue extracts evaluated by a pH stopped flow apparatus.", "content": "We have used a stopped flow rapid reaction pH apparatus to investigate the carbamate equilibrium in glycylglycine solutions and in three biological tissues, human plasma, sheep muscle, and sheep brain, as well as to investigate the kinetics of carbamate formation in glyclyglycine solution and in human plasma. The rapid reaction apparatus was equipped with a pH sensitive glass electrode in order to follow the time course of pH from 0.005 to 100 s after rapid mixing of a solution of amine or protein and CO2. Two phases of the pH curve were observed: a fast phase representing carbamate formation, and a slow phase due to the hydration of CO2 which was uncatalyzed since a carbonic anhydrase inhibitor was added to the biological solutions. From the time course of pH change during the fast phase K2, the R-NH2 ionization constant, and Kc, the carbamate equilibrium constant as well as the velocity constant for the formation of carbamate, ka could be calculated from data at different pH and pCO2. The carbamate formed in glycylglycine solutions over a wide range of pH and pCO2 was found consistent with the theory of carbamate formation and with published data. At ionic strength 0.16 and 37 degrees pK is 7.67. pKc 4.58. The heat of the carbamate reaction (deltaH) was calculated to be -3.2 kcal/mol between 20 degrees and 37 degrees. Kt of glycylglycine depends quantitatively on ionic strength as predicted by the Debye-Huckel theory. With ionic strength 0.16 ku was found to be 2,500 M1 S1 at 37 degrees. The activation energy of carbamate formation is 6.7 kcal/mol. Carbamate measurements in human plasma at pCO2 from 38 to 359 Torr. pH from 6.9 to 8.3, temperature 37 degrees, and ionic strength 0.15 provided evidence that two kinds of amino groups participate in carbamate formation. From the equilibrium constants computed for the two species they could be identified as alpha- and  epsilon-amino groups. On the basis of a protein molecular weight of 69.000. 0.6 alpha-amino groups/molecule with pKz=7.0 and pKc=4.2, and 5.9 epsilon-amino groups/molecule with pKz=9.0 and pKc=4.3 contribute to carbamate formation. The velocity constant ka was estimated to be 4,950 M1 S1 for the alpha-amino groups and 13,800 M1 S1 for the epsilon-amino groups. Under physiological conditions (pCO2=40 Torr. pH=7.4). The concentration of carbamate in plasma is 0.6 mM and the half-time of carbamate formation is 0.05 s. In extracts prepared from sheep brain at 37 degrees pH=7 and pCO2=35 Torr. the carbamate formation was estimated to be 0.8 mM. With pCO2=70 Torr and the same pH and temperature the carbamate concentration in muscle approximates 0.3 mM and increases to 7 mM as pH rises to 8. It is concluded that, as in plasma, a considerable number of epsilon-amino groups appear to be available for carbamate formation in these tissues.", "contents": "The carbamate reaction of glycylglycine, plasma, and tissue extracts evaluated by a pH stopped flow apparatus. We have used a stopped flow rapid reaction pH apparatus to investigate the carbamate equilibrium in glycylglycine solutions and in three biological tissues, human plasma, sheep muscle, and sheep brain, as well as to investigate the kinetics of carbamate formation in glyclyglycine solution and in human plasma. The rapid reaction apparatus was equipped with a pH sensitive glass electrode in order to follow the time course of pH from 0.005 to 100 s after rapid mixing of a solution of amine or protein and CO2. Two phases of the pH curve were observed: a fast phase representing carbamate formation, and a slow phase due to the hydration of CO2 which was uncatalyzed since a carbonic anhydrase inhibitor was added to the biological solutions. From the time course of pH change during the fast phase K2, the R-NH2 ionization constant, and Kc, the carbamate equilibrium constant as well as the velocity constant for the formation of carbamate, ka could be calculated from data at different pH and pCO2. The carbamate formed in glycylglycine solutions over a wide range of pH and pCO2 was found consistent with the theory of carbamate formation and with published data. At ionic strength 0.16 and 37 degrees pK is 7.67. pKc 4.58. The heat of the carbamate reaction (deltaH) was calculated to be -3.2 kcal/mol between 20 degrees and 37 degrees. Kt of glycylglycine depends quantitatively on ionic strength as predicted by the Debye-Huckel theory. With ionic strength 0.16 ku was found to be 2,500 M1 S1 at 37 degrees. The activation energy of carbamate formation is 6.7 kcal/mol. Carbamate measurements in human plasma at pCO2 from 38 to 359 Torr. pH from 6.9 to 8.3, temperature 37 degrees, and ionic strength 0.15 provided evidence that two kinds of amino groups participate in carbamate formation. From the equilibrium constants computed for the two species they could be identified as alpha- and  epsilon-amino groups. On the basis of a protein molecular weight of 69.000. 0.6 alpha-amino groups/molecule with pKz=7.0 and pKc=4.2, and 5.9 epsilon-amino groups/molecule with pKz=9.0 and pKc=4.3 contribute to carbamate formation. The velocity constant ka was estimated to be 4,950 M1 S1 for the alpha-amino groups and 13,800 M1 S1 for the epsilon-amino groups. Under physiological conditions (pCO2=40 Torr. pH=7.4). The concentration of carbamate in plasma is 0.6 mM and the half-time of carbamate formation is 0.05 s. In extracts prepared from sheep brain at 37 degrees pH=7 and pCO2=35 Torr. the carbamate formation was estimated to be 0.8 mM. With pCO2=70 Torr and the same pH and temperature the carbamate concentration in muscle approximates 0.3 mM and increases to 7 mM as pH rises to 8. It is concluded that, as in plasma, a considerable number of epsilon-amino groups appear to be available for carbamate formation in these tissues."}
{"id": "PMID:6480", "title": "The contractile basis of ameboid movement. II. Structure and contractility of motile extracts and plasmalemma-ectoplasm ghosts.", "content": "The role of calcium and magnesium-ATP on the structure and contractility in motile extracts of Amoeba proteus and plasmalemma-ectoplasm \"ghosts\" of Chaos carolinensis has been investigated by correlating light and electron microscope observations with turbidity and birefringence measurements. The extract is nonmotile and contains very few F-actin filaments and myosin aggregates when prepared in the presence of both low calcium ion and ATP concentrations at an ionic strength of I = 0.05, pH 6.8. The addition of 1.0 mM magnesium chloride, 1.0 mM ATP, in the presence of a low calcium ion concentration (relaxation solution) induced the formation of some fibrous bundles of actin without contracting, whereas the addition of a micromolar concentration of calcium in addition to 1.0 mM magnesium-ATP (contraction solution) (Taylor, D. L., J. S. Condeelis, P. L. Moore, and R. D. Allen. 1973. J. Cell Biol. 59:378-394) initiated the formation of large arrays of F-actin filaments followed by contractions. Furthermore, plasmalemma-ectoplasm ghosts prepared in the relaxation solution exhibited very few straight F-actin filaments and myosin aggregates. In contrast, plasmalemmaectoplasm ghosts treated with the contraction solution contained many straight F-actin filaments and myosin aggregates. The increase in the structure of ameba cytoplasm at the endoplasm-ectoplasm interface can be explained by a combination of the transformation of actin from a less filamentous to a more structured filamentous state possibly involving the cross-linking of actin to form fibrillar arrays (see above-mentioned reference) followed by contractions of the actin and myosin along an undetermined distance of the endoplasm and/or ectoplasm.", "contents": "The contractile basis of ameboid movement. II. Structure and contractility of motile extracts and plasmalemma-ectoplasm ghosts. The role of calcium and magnesium-ATP on the structure and contractility in motile extracts of Amoeba proteus and plasmalemma-ectoplasm \"ghosts\" of Chaos carolinensis has been investigated by correlating light and electron microscope observations with turbidity and birefringence measurements. The extract is nonmotile and contains very few F-actin filaments and myosin aggregates when prepared in the presence of both low calcium ion and ATP concentrations at an ionic strength of I = 0.05, pH 6.8. The addition of 1.0 mM magnesium chloride, 1.0 mM ATP, in the presence of a low calcium ion concentration (relaxation solution) induced the formation of some fibrous bundles of actin without contracting, whereas the addition of a micromolar concentration of calcium in addition to 1.0 mM magnesium-ATP (contraction solution) (Taylor, D. L., J. S. Condeelis, P. L. Moore, and R. D. Allen. 1973. J. Cell Biol. 59:378-394) initiated the formation of large arrays of F-actin filaments followed by contractions. Furthermore, plasmalemma-ectoplasm ghosts prepared in the relaxation solution exhibited very few straight F-actin filaments and myosin aggregates. In contrast, plasmalemmaectoplasm ghosts treated with the contraction solution contained many straight F-actin filaments and myosin aggregates. The increase in the structure of ameba cytoplasm at the endoplasm-ectoplasm interface can be explained by a combination of the transformation of actin from a less filamentous to a more structured filamentous state possibly involving the cross-linking of actin to form fibrillar arrays (see above-mentioned reference) followed by contractions of the actin and myosin along an undetermined distance of the endoplasm and/or ectoplasm."}
{"id": "PMID:6481", "title": "Variation in aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity in heteroploid and predominantly diploid rat liver cells in culture.", "content": "Aryl hydrocarbon (benzo(a)pyrene) hydroxylase is present and inducible in Buffalo rat liver cells in culture. There is substantial variation in both basal and inducible hydroxylase activities among heteroploid subclones isolated from a heteroploid parent population, and among diploid subclones isolated from a diploid parent population. This variation is not related to differences in the growth characteristics of the subclones, or to differences in their chromosome number. The results indicate that substantial heterogeneity in both basal and induced hydroxylase activity develops during the growth of both heteroploid and diploid cell strains in culture. These findings indicate that diploid cell populations are not necessarily homogeneous with respect to aryl hydrocarbon hydroxylas activity. This observation may complicate the interpretation of experiments involving somatic cell hybridization or polycyclic hydrocarbon-induced transformation and/or cytotoxicity. This heterogeneity in hydroxylase activity develops rather rapidly (2-3 mo of culture), in the absence of any apparent mutational stress.", "contents": "Variation in aryl hydrocarbon (benzo(a)pyrene) hydroxylase activity in heteroploid and predominantly diploid rat liver cells in culture. Aryl hydrocarbon (benzo(a)pyrene) hydroxylase is present and inducible in Buffalo rat liver cells in culture. There is substantial variation in both basal and inducible hydroxylase activities among heteroploid subclones isolated from a heteroploid parent population, and among diploid subclones isolated from a diploid parent population. This variation is not related to differences in the growth characteristics of the subclones, or to differences in their chromosome number. The results indicate that substantial heterogeneity in both basal and induced hydroxylase activity develops during the growth of both heteroploid and diploid cell strains in culture. These findings indicate that diploid cell populations are not necessarily homogeneous with respect to aryl hydrocarbon hydroxylas activity. This observation may complicate the interpretation of experiments involving somatic cell hybridization or polycyclic hydrocarbon-induced transformation and/or cytotoxicity. This heterogeneity in hydroxylase activity develops rather rapidly (2-3 mo of culture), in the absence of any apparent mutational stress."}
{"id": "PMID:6484", "title": "Isocratic separation of some purine nucleotide, nucleoside, and base metabolites from biological extracts by high-performance liquid chromatography.", "content": "Separation of ATP, ADP, AMP, adenine, adenosine, cAMP, ITP, IDP, IMP, hypoxanthine, inosine, cIMP, the guanine series, NAD, NADPH, xanthine, 3-methylxanthine, theobromine, theophylline, and caffeine was accomplished using high-performance liquid chromatography with a microparticulate reversed-phase column. Under isocratic conditions all compounds could be eluted with reasonable resolution and retention time. Quantitation by peak height for several of the compounds was used to the 10-ng level.", "contents": "Isocratic separation of some purine nucleotide, nucleoside, and base metabolites from biological extracts by high-performance liquid chromatography. Separation of ATP, ADP, AMP, adenine, adenosine, cAMP, ITP, IDP, IMP, hypoxanthine, inosine, cIMP, the guanine series, NAD, NADPH, xanthine, 3-methylxanthine, theobromine, theophylline, and caffeine was accomplished using high-performance liquid chromatography with a microparticulate reversed-phase column. Under isocratic conditions all compounds could be eluted with reasonable resolution and retention time. Quantitation by peak height for several of the compounds was used to the 10-ng level."}
{"id": "PMID:6486", "title": "Synthetic MIF has no effect on beta-MSH and ACTH hypersecretion in Nelson's syndrome.", "content": "The effect of synthetic MIF (H-Pro-Leu-Gly-NH2) on beta-MSH secretion was studied in five patients with Nelson's syndrome and in one patient with Addison's disease. Two milligrams of the tripetide were injected intravenously (1 mg in an acute injection, followed by a 30-minute-infusion of 1 mg in 20 ml of saline solution). No consistent effect could be observed during the 90-minute period after the beginning of the infusion. In the same patients, LVP stimulation and dexamethasone suppression tests brought about significant changes in the plasma beta-MSH and ACTH levels.", "contents": "Synthetic MIF has no effect on beta-MSH and ACTH hypersecretion in Nelson's syndrome. The effect of synthetic MIF (H-Pro-Leu-Gly-NH2) on beta-MSH secretion was studied in five patients with Nelson's syndrome and in one patient with Addison's disease. Two milligrams of the tripetide were injected intravenously (1 mg in an acute injection, followed by a 30-minute-infusion of 1 mg in 20 ml of saline solution). No consistent effect could be observed during the 90-minute period after the beginning of the infusion. In the same patients, LVP stimulation and dexamethasone suppression tests brought about significant changes in the plasma beta-MSH and ACTH levels."}
{"id": "PMID:6487", "title": "Description of a polyvalent conjugate and a new serogroup of Bacteroides melaninogenicus by fluorescent antibody staining.", "content": "A polyvalent conjugate (fluorescein isothiocyanate-labeled antibody reagent) containing serogroups A, B, and C conjugates was prepared. This polyvalent conjugate gave a positive fluorescent antibody (FA) stain with 49 stains of Bacteroides melaninogenicus representing serogroups A, B, and C. When additional strains (92 strains) of the three subspecies of B. melaninogenicus were examined by the FA stain, with A, B, and C, and polyvalent conjugates, nine strains of B. melaninogenicus subsp. intermedius failed to give a positive stain with any conjugate. Therefore, an FA conjugate was prepared with the antiserum to one of these strains (532-70A); all nine strains stained positively with this conjugate. These nine strains were biochemically characteristic of B. melaninogenicus subsp. intermedius; thus, these strains were designated as a new serogroup, serogroup C-1. A new polyvalent conjugate containing serogroups A, B, C, and C-1 was prepared. This polyvalent conjugate stained positively with 23 representative strains from serogroups A, B, C, and C-1. The new conjugates failed to stain positively with other anaerobes and aerobes tested. The four individual conjugates, as well as the polyvalent conjugate, may be used for a more rapid identification of B. melaninogenicus than is possible by biochemical testing.", "contents": "Description of a polyvalent conjugate and a new serogroup of Bacteroides melaninogenicus by fluorescent antibody staining. A polyvalent conjugate (fluorescein isothiocyanate-labeled antibody reagent) containing serogroups A, B, and C conjugates was prepared. This polyvalent conjugate gave a positive fluorescent antibody (FA) stain with 49 stains of Bacteroides melaninogenicus representing serogroups A, B, and C. When additional strains (92 strains) of the three subspecies of B. melaninogenicus were examined by the FA stain, with A, B, and C, and polyvalent conjugates, nine strains of B. melaninogenicus subsp. intermedius failed to give a positive stain with any conjugate. Therefore, an FA conjugate was prepared with the antiserum to one of these strains (532-70A); all nine strains stained positively with this conjugate. These nine strains were biochemically characteristic of B. melaninogenicus subsp. intermedius; thus, these strains were designated as a new serogroup, serogroup C-1. A new polyvalent conjugate containing serogroups A, B, C, and C-1 was prepared. This polyvalent conjugate stained positively with 23 representative strains from serogroups A, B, C, and C-1. The new conjugates failed to stain positively with other anaerobes and aerobes tested. The four individual conjugates, as well as the polyvalent conjugate, may be used for a more rapid identification of B. melaninogenicus than is possible by biochemical testing."}
{"id": "PMID:6488", "title": "Regulation of acid-base equilibrium in chronic hypocapnia. Evidence that the response of the kidney is not geared to the defense of extracellular (H+).", "content": "It is generally believed that the reduction in plasma [HCO3] characteristic of chronic hypocapnia results from renal homeostatic mechanisms designed to minimize the alkalemia produced by.the hypocapneic state. To test this hypothesis, we have induced chronic hypocapnia in dogs in which plasma [HCO3] had previously been markedly reduced (from 21 to 15 meq/liter) by the prolonged feeding of HCl. The PaCO2 of chronically acid-fed animals was reduced from 32 to 15 mm Hg by placing the animials in a large environmental chamber containing 9% oxygen. In response to this reduction in PaCO2, mean plasma [HCO3] fell by 8.6 meq/liter, reaching a new steady-state level of 6.4 meq/liter. This decrement in plasma [HCO3] is almost identical to the 8.1 meq/liter decrement previously observed in normal (nonacid-fed) animals in which the same degree of chronic hypocapnia had been induced. Thus, in both normal and HCl-fed animals, the renal response to chronic hypocapnia causes plasma [HCO3] to fall by approximately 0.5 meq/liter for each millimeter of Hg reduction in CO2 tension. By contrast, the response of plasma [H+] in the two groups was markedly different. Instead of the fall in [H+] which is seen during chronic hypocapnia in normal animals, [H+] in HCl-fed animals rose significantly from 53 to 59 neq/liter (pH 7.28-7.23). This seemingly paradoxical response is, of course, an expression of the constraints imposed by the Henderson equation and reflects the fact that the percent fall in [HCO3] in the HCl-fed animals was greater than the percent fall in PaCO2. These findings clearly indicate that in chronic hypocapnia the kidney cannot be regarded as the effector limb in a homeostatic feedback system geared to the defense of systemic acidity.", "contents": "Regulation of acid-base equilibrium in chronic hypocapnia. Evidence that the response of the kidney is not geared to the defense of extracellular (H+). It is generally believed that the reduction in plasma [HCO3] characteristic of chronic hypocapnia results from renal homeostatic mechanisms designed to minimize the alkalemia produced by.the hypocapneic state. To test this hypothesis, we have induced chronic hypocapnia in dogs in which plasma [HCO3] had previously been markedly reduced (from 21 to 15 meq/liter) by the prolonged feeding of HCl. The PaCO2 of chronically acid-fed animals was reduced from 32 to 15 mm Hg by placing the animials in a large environmental chamber containing 9% oxygen. In response to this reduction in PaCO2, mean plasma [HCO3] fell by 8.6 meq/liter, reaching a new steady-state level of 6.4 meq/liter. This decrement in plasma [HCO3] is almost identical to the 8.1 meq/liter decrement previously observed in normal (nonacid-fed) animals in which the same degree of chronic hypocapnia had been induced. Thus, in both normal and HCl-fed animals, the renal response to chronic hypocapnia causes plasma [HCO3] to fall by approximately 0.5 meq/liter for each millimeter of Hg reduction in CO2 tension. By contrast, the response of plasma [H+] in the two groups was markedly different. Instead of the fall in [H+] which is seen during chronic hypocapnia in normal animals, [H+] in HCl-fed animals rose significantly from 53 to 59 neq/liter (pH 7.28-7.23). This seemingly paradoxical response is, of course, an expression of the constraints imposed by the Henderson equation and reflects the fact that the percent fall in [HCO3] in the HCl-fed animals was greater than the percent fall in PaCO2. These findings clearly indicate that in chronic hypocapnia the kidney cannot be regarded as the effector limb in a homeostatic feedback system geared to the defense of systemic acidity."}
{"id": "PMID:6489", "title": "Characterization of the protease activity in the chemotactic factor inactivator.", "content": "The chemotactic factor inactivator (CFI) isolated from human serum contains a kininase activity that causes extensive hydrolysis of bradykinin. The highly chemotactic synthetic peptide Met-Leu-Phe was completely hydrolyzed by CFI preparations. The release of the constituent amino acids from this peptide coincided with a loss of its chemotactic activity. The N-formyl, but not the amide derivative, of the leukotactic peptide Met-Leu-Phe was resistant to the action of CFI, as evidenced by chemotactic and biochemical assays. Examination of the specificity of CFI proteolysis revealed that short polypeptide substrates are degraded sequentially from the amino terminus. Larger peptides are less extensively hydrolyzed, and the patterns of hydrolysis are more complex. Inactivation of the bacterial chemotactic factors by CFI was overcome by the addition of high concentrations of peptides which were substrated for CFI. CFI preparations readily hydrolyzed the peptide Arg-Phe-Ala. The constituent amino acids were conveniently identified by thin-layer chromatography method. This procedure afforded a rapid assay for measuring CFI activity in the whole human serum as well as in fractions throughout the purification steps. Moreover, CFI also hydrolyzed L-leucyl-beta-napthylamide at rates comparable to peptides. Thus, L-leucyl-beta-napthylamide served as a useful substrate for estimating  CFI activity in preparations at various stages of purification. This substrate was also useful in kinetic studies. The results from these studies indicate an aminopeptidase activity is the mechanism whereby CFI inhibits the activity of chemotactic substrates.", "contents": "Characterization of the protease activity in the chemotactic factor inactivator. The chemotactic factor inactivator (CFI) isolated from human serum contains a kininase activity that causes extensive hydrolysis of bradykinin. The highly chemotactic synthetic peptide Met-Leu-Phe was completely hydrolyzed by CFI preparations. The release of the constituent amino acids from this peptide coincided with a loss of its chemotactic activity. The N-formyl, but not the amide derivative, of the leukotactic peptide Met-Leu-Phe was resistant to the action of CFI, as evidenced by chemotactic and biochemical assays. Examination of the specificity of CFI proteolysis revealed that short polypeptide substrates are degraded sequentially from the amino terminus. Larger peptides are less extensively hydrolyzed, and the patterns of hydrolysis are more complex. Inactivation of the bacterial chemotactic factors by CFI was overcome by the addition of high concentrations of peptides which were substrated for CFI. CFI preparations readily hydrolyzed the peptide Arg-Phe-Ala. The constituent amino acids were conveniently identified by thin-layer chromatography method. This procedure afforded a rapid assay for measuring CFI activity in the whole human serum as well as in fractions throughout the purification steps. Moreover, CFI also hydrolyzed L-leucyl-beta-napthylamide at rates comparable to peptides. Thus, L-leucyl-beta-napthylamide served as a useful substrate for estimating  CFI activity in preparations at various stages of purification. This substrate was also useful in kinetic studies. The results from these studies indicate an aminopeptidase activity is the mechanism whereby CFI inhibits the activity of chemotactic substrates."}
{"id": "PMID:6490", "title": "Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases.", "content": "Antibody-dependent cell-mediated cytotoxicity mediated by peripheral blood lymphocytes was studied in patients with systemic lupus erythematosus, polyarteritis nodosa. Sjogren's syndrome, and rheumatoid arthritis. The target cells were chicken erythrocytes coated with rabbit anti-chicken erythrocyte antibody. Antibody-dependent cell-mediated cytotoxic activity was normal in Sjogren's syndrome and rheumatoid arthritis but significantly decreased (P is less than 0.001) in active systemic lupus erythematosus and in two patients with polyarteritis nodosa. A partial regeneration of antibody-dependent cell-mediated cytotoxic activity was obtained by treatment with pronase and DNase followed by overnight incubation. Sera from patients with systemic lupus erythematosus inhibited antibody-dependent cell-mediated cytotoxic activity of normal lymphocytes. The inhibitory activity was studied by specific immunoadsorption and sucrose density geadient ultracentrifugation. Removal of IgG but not IgM greatly reduced inhibition. Inhibitory factors were present in 7S and heavier fractions containing IgG. Five systemic lupus erythematosus patients were studied serially to determine if improvement in clinical status could be correlated with a decrease in serum inhibitory factors as studied by inhibition of normal antibody-dependent cell-mediated cytotoxicity. Indeed, a greater serum inhibitory capacity was found in each patient during periods of greater disease activity.", "contents": "Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases. Antibody-dependent cell-mediated cytotoxicity mediated by peripheral blood lymphocytes was studied in patients with systemic lupus erythematosus, polyarteritis nodosa. Sjogren's syndrome, and rheumatoid arthritis. The target cells were chicken erythrocytes coated with rabbit anti-chicken erythrocyte antibody. Antibody-dependent cell-mediated cytotoxic activity was normal in Sjogren's syndrome and rheumatoid arthritis but significantly decreased (P is less than 0.001) in active systemic lupus erythematosus and in two patients with polyarteritis nodosa. A partial regeneration of antibody-dependent cell-mediated cytotoxic activity was obtained by treatment with pronase and DNase followed by overnight incubation. Sera from patients with systemic lupus erythematosus inhibited antibody-dependent cell-mediated cytotoxic activity of normal lymphocytes. The inhibitory activity was studied by specific immunoadsorption and sucrose density geadient ultracentrifugation. Removal of IgG but not IgM greatly reduced inhibition. Inhibitory factors were present in 7S and heavier fractions containing IgG. Five systemic lupus erythematosus patients were studied serially to determine if improvement in clinical status could be correlated with a decrease in serum inhibitory factors as studied by inhibition of normal antibody-dependent cell-mediated cytotoxicity. Indeed, a greater serum inhibitory capacity was found in each patient during periods of greater disease activity."}
{"id": "PMID:6491", "title": "The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.", "content": "Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man.", "contents": "The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man. Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man."}
{"id": "PMID:6492", "title": "The effect of hyperventilation on distal nephron hydrogen ion secretion.", "content": "This study was designed to determine the effect of acute hyperventilation on distal nephron hydrogen ion secretion. The blood PCO2 declined and stabilized rapidly when bicarbonate loaded rats were hyperventilated. In contrast, the urine PCO2 declined slowly, resulting in an early increase in the urine minus blood (U-B) PCO2 which could not be obliterated by carbonic anhydrase infusion. Within approximately 50 min, the U-B PCO2 in the hyperventilated and carbonic anhydrase infused rats approached zero. Consequently, equilibrium between collecting duct urine and arterial blood PCO2 was then presumed to exist. This provided the basis for the subsequent studies on a series of rats. The U-B PCO2 decreased from a control of 22+/-1 mm Hg (mean+/-SEM) to 11+/-2 mm Hg (mean+/-SEM) with hypocapnia, and rose again to its control value when the blood PCO2 returned to prehyperventilation values. This decline in U-B PCO2 with acute hyperventilation could not be attributed to changes in urine flow, phosphate, or bicarbonate excretion, suggesting, therefore, a decrease in distal nephron (probably collecting duct) hydrogen ion secretion with acute hyperventilation. Possible pitfalls in the interpretation of the UB PCO2 are illustrated.", "contents": "The effect of hyperventilation on distal nephron hydrogen ion secretion. This study was designed to determine the effect of acute hyperventilation on distal nephron hydrogen ion secretion. The blood PCO2 declined and stabilized rapidly when bicarbonate loaded rats were hyperventilated. In contrast, the urine PCO2 declined slowly, resulting in an early increase in the urine minus blood (U-B) PCO2 which could not be obliterated by carbonic anhydrase infusion. Within approximately 50 min, the U-B PCO2 in the hyperventilated and carbonic anhydrase infused rats approached zero. Consequently, equilibrium between collecting duct urine and arterial blood PCO2 was then presumed to exist. This provided the basis for the subsequent studies on a series of rats. The U-B PCO2 decreased from a control of 22+/-1 mm Hg (mean+/-SEM) to 11+/-2 mm Hg (mean+/-SEM) with hypocapnia, and rose again to its control value when the blood PCO2 returned to prehyperventilation values. This decline in U-B PCO2 with acute hyperventilation could not be attributed to changes in urine flow, phosphate, or bicarbonate excretion, suggesting, therefore, a decrease in distal nephron (probably collecting duct) hydrogen ion secretion with acute hyperventilation. Possible pitfalls in the interpretation of the UB PCO2 are illustrated."}
{"id": "PMID:6493", "title": "Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina.", "content": "The activities of guanylate cyclase, guanosine 3', 5'-monophosphate (cyclic GMP) phosphodiesterase and 5'-nucleotidase were measured during postnatal development in retinas of control and C3H/HeJ mice. In control retina, each of these enzyme activities increases in conjunction with photoreceptor cell differentiation and maturation. In C3H retina, guanylate cyclase and 5-nucleotidase activities increase with photoreceptor cell development and decrease with photoreceptor cell death. However, the activity of a class of cyclic GMP phosphodiesterase which distinguishes the photoreceptor cells of control mice and those of several other species is not demonstrable in retina of C3H mice at any age. It is suggested that the deficiency in cyclic GMP phosphodiesterase activity may account for the accumulation of cyclic GMP which has been shown to occur in the C3H photoreceptor cells before they degenerate.", "contents": "Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina. The activities of guanylate cyclase, guanosine 3', 5'-monophosphate (cyclic GMP) phosphodiesterase and 5'-nucleotidase were measured during postnatal development in retinas of control and C3H/HeJ mice. In control retina, each of these enzyme activities increases in conjunction with photoreceptor cell differentiation and maturation. In C3H retina, guanylate cyclase and 5-nucleotidase activities increase with photoreceptor cell development and decrease with photoreceptor cell death. However, the activity of a class of cyclic GMP phosphodiesterase which distinguishes the photoreceptor cells of control mice and those of several other species is not demonstrable in retina of C3H mice at any age. It is suggested that the deficiency in cyclic GMP phosphodiesterase activity may account for the accumulation of cyclic GMP which has been shown to occur in the C3H photoreceptor cells before they degenerate."}
{"id": "PMID:6494", "title": "beta-Adrenergic receptors in rat brain.", "content": "125I-Iodohydroxybenzylpindolol ([125I] IHYP), a potent beta-adrenergic receptor antagonist, has been used to study beta-adrenergic receptors in rat brain. Binding of [125I] IHYP (30 pM) to a membrane fraction min and dissociation took place with a half time of about 16 min. Phentolamine (10(-4) M) decreased non-receptor binding but it had no effect on the binding of [125I] IHYP to beta-adrenergic receptors in cortex, cerebellum or caudate. In the presence of phentolamine specific binding (defined as binding which was blocked by 0.3 muM dl-propranolol) represented 70-85% of total binding. The binding of [125I] IHYP was inhibited by beta-adrenergic agonists and antagonists. d-Stereoisomers were 2-3 orders of magnitude less potent than the corresponding 1-isomers. The denstiy of [125I] IHYP binding sites was studied in membrane fractions from cerebral cortex, cerebellum, and caudate nucleus by means of Scatchard analysis. The K(D) of [125I] IHYP was similar in the three regions studied, and the density of [125I] IHYP binding sites was approximately 50% greater in the cortex and caudate than in the cerebellum. The Hill coefficient for the binding of [125I] IHYP to membranes from cerebral cortex was 1.02. The properties of the binding of [125I] IHYP are similar to those which would be expected of binding to beta-adrenergic receptors in vitro.", "contents": "beta-Adrenergic receptors in rat brain. 125I-Iodohydroxybenzylpindolol ([125I] IHYP), a potent beta-adrenergic receptor antagonist, has been used to study beta-adrenergic receptors in rat brain. Binding of [125I] IHYP (30 pM) to a membrane fraction min and dissociation took place with a half time of about 16 min. Phentolamine (10(-4) M) decreased non-receptor binding but it had no effect on the binding of [125I] IHYP to beta-adrenergic receptors in cortex, cerebellum or caudate. In the presence of phentolamine specific binding (defined as binding which was blocked by 0.3 muM dl-propranolol) represented 70-85% of total binding. The binding of [125I] IHYP was inhibited by beta-adrenergic agonists and antagonists. d-Stereoisomers were 2-3 orders of magnitude less potent than the corresponding 1-isomers. The denstiy of [125I] IHYP binding sites was studied in membrane fractions from cerebral cortex, cerebellum, and caudate nucleus by means of Scatchard analysis. The K(D) of [125I] IHYP was similar in the three regions studied, and the density of [125I] IHYP binding sites was approximately 50% greater in the cortex and caudate than in the cerebellum. The Hill coefficient for the binding of [125I] IHYP to membranes from cerebral cortex was 1.02. The properties of the binding of [125I] IHYP are similar to those which would be expected of binding to beta-adrenergic receptors in vitro."}
{"id": "PMID:6495", "title": "Effects of citrus pulp in high urea rations for steers.", "content": "Effects of pelleted and conventional citrus pulp as a replacement for corn, with soybean meal added to keep protein comparable, were tested in rations with 5% urea and 33.33% sugarcane bagasse for fistulated steers. Thus, all rations were low in readily fermented carbohydrates other than those of corn or citrus pulp. Evaluation criteria were concentrations of urea in blood and of pH, ammonia, and volatile fatty acids of rumen fluid. Citrus pulp for diets 1, 2, 3, and 4 was 0, 19, 38, or 55%. Rumen fluid and blood were sampled 1 h before and 2, 4, 7, and 12 h after feed was placed directly into the rumen. No differences between pelleted and conventional pulp or among time trends were significant except that for both forms rumen ammonia was lower with the two highest percents of citrus pulp. Addition of citrus pulp at 0, 19, 38, or 55% of the ration reduced rumen pH (6.85, 6.65, 6.61, 6.51). Blood urea and rumen ammonia decreased in steers fed 19, 38, or 55% pulp; thus, the acetic to propionic ratio was higher. Butyric acid changed only in the time trend. Total volatile fatty acid concentrations were higher at 19, 38, and 55% than at 0% pulp. They were higher at 38 and 55 than at 19%.", "contents": "Effects of citrus pulp in high urea rations for steers. Effects of pelleted and conventional citrus pulp as a replacement for corn, with soybean meal added to keep protein comparable, were tested in rations with 5% urea and 33.33% sugarcane bagasse for fistulated steers. Thus, all rations were low in readily fermented carbohydrates other than those of corn or citrus pulp. Evaluation criteria were concentrations of urea in blood and of pH, ammonia, and volatile fatty acids of rumen fluid. Citrus pulp for diets 1, 2, 3, and 4 was 0, 19, 38, or 55%. Rumen fluid and blood were sampled 1 h before and 2, 4, 7, and 12 h after feed was placed directly into the rumen. No differences between pelleted and conventional pulp or among time trends were significant except that for both forms rumen ammonia was lower with the two highest percents of citrus pulp. Addition of citrus pulp at 0, 19, 38, or 55% of the ration reduced rumen pH (6.85, 6.65, 6.61, 6.51). Blood urea and rumen ammonia decreased in steers fed 19, 38, or 55% pulp; thus, the acetic to propionic ratio was higher. Butyric acid changed only in the time trend. Total volatile fatty acid concentrations were higher at 19, 38, and 55% than at 0% pulp. They were higher at 38 and 55 than at 19%."}
{"id": "PMID:6499", "title": "Aspirin-induced gastritis and gastrointestinal bleeding.", "content": "Aspirin-induced gastritis and gastrointestinal hemorrhage were reviewed and discussed on the basis of currently available literature. Acute hemorrhagic gastritis occurs in from 50% to 70% of all patients taking aspirin, is not directly related to dose size, and can be severe enough to cause death in a few cases. No tolerance appears to ever develop. The mechanism that causes this bleeding is not definite, but the back diffusion of H+ ions accross the gastric barrier seems to bear primary responsibility, with physical erosion, prolonged platelet bleeding, and the effect of low pH values also being possible explanations. There appears to be less acid present in the stomach when bleeding occurs, but this is a masking effect of the aspirin that causes increased absorption of the H+ ions. Factors important in determining pharmaceutical formulation are method of administration, particle size of the aspirin, duration of contact between the drug and the mucosa, presence of buffers in the drug to raise the gastric pH, dissolution rate of the drug in the stomach, and ionization characteristics of the drug itself. Gastrointestinal blood loss caused by aspirin can be minimized by administering the drug in one of these forms:--a dilute solution of acetylsalicylate;--an intravenously injected solution;--a very rapidly dissolving and rapidly absorbed tablet;--a solution with sufficiently large amounts of antacid added;--a fine-grain, highly buffered aspirin tablet;--an enteric-coated tablet that does not dissolve in the stomach; or--an aspirin substitute such as acetaminophen.", "contents": "Aspirin-induced gastritis and gastrointestinal bleeding. Aspirin-induced gastritis and gastrointestinal hemorrhage were reviewed and discussed on the basis of currently available literature. Acute hemorrhagic gastritis occurs in from 50% to 70% of all patients taking aspirin, is not directly related to dose size, and can be severe enough to cause death in a few cases. No tolerance appears to ever develop. The mechanism that causes this bleeding is not definite, but the back diffusion of H+ ions accross the gastric barrier seems to bear primary responsibility, with physical erosion, prolonged platelet bleeding, and the effect of low pH values also being possible explanations. There appears to be less acid present in the stomach when bleeding occurs, but this is a masking effect of the aspirin that causes increased absorption of the H+ ions. Factors important in determining pharmaceutical formulation are method of administration, particle size of the aspirin, duration of contact between the drug and the mucosa, presence of buffers in the drug to raise the gastric pH, dissolution rate of the drug in the stomach, and ionization characteristics of the drug itself. Gastrointestinal blood loss caused by aspirin can be minimized by administering the drug in one of these forms:--a dilute solution of acetylsalicylate;--an intravenously injected solution;--a very rapidly dissolving and rapidly absorbed tablet;--a solution with sufficiently large amounts of antacid added;--a fine-grain, highly buffered aspirin tablet;--an enteric-coated tablet that does not dissolve in the stomach; or--an aspirin substitute such as acetaminophen."}
{"id": "PMID:6504", "title": "Urologic sepsis/shock.", "content": "At Columbia-Presbyterian Medical Center during the six-year period 1968-1973, there were 1236 cases of sepsis from Gram-negative pathogens; 124 of these originated in the urinary tract. Of these 124 patients, 19 died-a mortality rate of 15.3 percent. There were 205 deaths among the 1236 patients with sepsis from Gramnegative organisms-a mortality rate of 16.6 percent. Previously, in the 1959-1964 and 1965-19067 periods, the mortality rates had been 56.3 percent and 19.6 percent respectively. The lowered mortality rate during 1968-1973 for urologic sepsis/shock was associated with improved management procedures: a) preventive measures such as postponement of urologic instrumentation and surgical intervention in patients infected with drug-resistant urea splitters, until the infection is under control, with emergency surgical patients being treated by susceptibility-tested drugs to control possible postoperative complications; b) early diagnosis and treatment of sepsis and immediate administration of bactericidal antibiotics parenterally; c) immediate restoration of fluid/electrolyte balance, with monitoring of renal and pulmonary functions and metabolic acidosis; and d) early administration of large pharmacologic doses of glucocorticoids, with monitoring of the microcirculation and use of beta-adrenergic isoproterenol.", "contents": "Urologic sepsis/shock. At Columbia-Presbyterian Medical Center during the six-year period 1968-1973, there were 1236 cases of sepsis from Gram-negative pathogens; 124 of these originated in the urinary tract. Of these 124 patients, 19 died-a mortality rate of 15.3 percent. There were 205 deaths among the 1236 patients with sepsis from Gramnegative organisms-a mortality rate of 16.6 percent. Previously, in the 1959-1964 and 1965-19067 periods, the mortality rates had been 56.3 percent and 19.6 percent respectively. The lowered mortality rate during 1968-1973 for urologic sepsis/shock was associated with improved management procedures: a) preventive measures such as postponement of urologic instrumentation and surgical intervention in patients infected with drug-resistant urea splitters, until the infection is under control, with emergency surgical patients being treated by susceptibility-tested drugs to control possible postoperative complications; b) early diagnosis and treatment of sepsis and immediate administration of bactericidal antibiotics parenterally; c) immediate restoration of fluid/electrolyte balance, with monitoring of renal and pulmonary functions and metabolic acidosis; and d) early administration of large pharmacologic doses of glucocorticoids, with monitoring of the microcirculation and use of beta-adrenergic isoproterenol."}
{"id": "PMID:6505", "title": "[Study of fetal heart rate in deliveries complicated by fetal acidosis].", "content": "A study has been carried out on the parameters of the graph of the fetal heart rate (the basal rate and dips) in 44 cases of acute fetal distress with a pH lower than 7.2 in the blood and in 30 normal deliveries. The statistical analysis confirms that there is a significant rise in the number of heart rate abnormalities such as persistent bradycardia or persistent tachycardia and with dips during deliveries with fetal acidosis. The frequency of these abnormalities increases with the degree of acidosis. Sometimes the abnormalities in the fetal heart rate precede the appearance of the acidosis. All the same the discovery of these abnormalities does not by itself make a precise diagnosis of fetal distress because we do find these abnormalities in a certain number of cases even in normal deliveries. Only measuring fetal pH at a definite time can establish the diagnosis of fetal distress and the severity of the condition.", "contents": "[Study of fetal heart rate in deliveries complicated by fetal acidosis]. A study has been carried out on the parameters of the graph of the fetal heart rate (the basal rate and dips) in 44 cases of acute fetal distress with a pH lower than 7.2 in the blood and in 30 normal deliveries. The statistical analysis confirms that there is a significant rise in the number of heart rate abnormalities such as persistent bradycardia or persistent tachycardia and with dips during deliveries with fetal acidosis. The frequency of these abnormalities increases with the degree of acidosis. Sometimes the abnormalities in the fetal heart rate precede the appearance of the acidosis. All the same the discovery of these abnormalities does not by itself make a precise diagnosis of fetal distress because we do find these abnormalities in a certain number of cases even in normal deliveries. Only measuring fetal pH at a definite time can establish the diagnosis of fetal distress and the severity of the condition."}
{"id": "PMID:6591", "title": "The cleaning and disinfection by heat of bedpans in automatic and semi-automatic machines.", "content": "This work is concerned with the cleaning and disinfection by heat of stainless-steel and polypropylene bedpans, which had been soiled with either a biological contaminant, human serum albumin (HSA) labelled with technetium-99m 99m(Tc), or a bacteriological contaminant, streptococcus faecalis mixed with Tc-labelled HSA. Results of cleaning and disinfection achieved with a Test Machine and those achieved by procedures adopted in eight different wards of a general hospital are reported. Bedpan washers installed in wards were found to be less efficient than the Test Machine, at least partly because of inadequate maintenance. Stainless-steel and polypropylene bedpans gave essentially the same results.", "contents": "The cleaning and disinfection by heat of bedpans in automatic and semi-automatic machines. This work is concerned with the cleaning and disinfection by heat of stainless-steel and polypropylene bedpans, which had been soiled with either a biological contaminant, human serum albumin (HSA) labelled with technetium-99m 99m(Tc), or a bacteriological contaminant, streptococcus faecalis mixed with Tc-labelled HSA. Results of cleaning and disinfection achieved with a Test Machine and those achieved by procedures adopted in eight different wards of a general hospital are reported. Bedpan washers installed in wards were found to be less efficient than the Test Machine, at least partly because of inadequate maintenance. Stainless-steel and polypropylene bedpans gave essentially the same results."}
{"id": "PMID:6592", "title": "Factors affecting the sensitivity of replicating McCoy cells in the isolation and growth of chlamydia A (TRIC agents).", "content": "Normal non-irradiated McCoy cell cultures provide a sensitive and reproducible method for the isolation of oculo-genital strains of chlamydia A directly from human secretions and for laboratory studies with these agents. Since September 1973, chlamydia have been isolated from 175 of 562 women (32-1%) attending venereal disease clinics. Freshly isolated and low passage strains have been used to determine the importance of centrifugation, constitution and pH of the tissue culture medium, and the temperature of incubation in controlling the efficiency of plating in the method.", "contents": "Factors affecting the sensitivity of replicating McCoy cells in the isolation and growth of chlamydia A (TRIC agents). Normal non-irradiated McCoy cell cultures provide a sensitive and reproducible method for the isolation of oculo-genital strains of chlamydia A directly from human secretions and for laboratory studies with these agents. Since September 1973, chlamydia have been isolated from 175 of 562 women (32-1%) attending venereal disease clinics. Freshly isolated and low passage strains have been used to determine the importance of centrifugation, constitution and pH of the tissue culture medium, and the temperature of incubation in controlling the efficiency of plating in the method."}
{"id": "PMID:6593", "title": "Effect of six weekly transfusions on canine marrow grafts: tests for sensitization and abrogation of sensitization by procarbazine and antithymocyte serum.", "content": "We have previously shown that blood transfusions can immunize a dog and lead to rejection of a subsequent marrow graft despite lethal total body irradiation (TBI). Sensitization to histocompatibility antigens induced by two prior transfusions of whole blood could be overcome by a regimen of procarbazine and anti-thymocyte serum (ATS) preceding TBI. The current study investigated a) whether this regimen could abrogate sensitization induced by six weekly transfusions given from days --50 to --15 preceding a marrow graft, and b) whether platelet survival studies and two in vitro tests of immunity could predict marrow graft rejection. All donor-recipient pairs were histoincompatible, unrelated, and of different breed. Twenty-two recipients received platelet concentrate transfusions and eight received whole blood transfusions. Recipients were given 1200 R TBI and a graft of marrow and peripheral blood leukocytes from the transfusion donor on day 0. Three of 15 recipients (20%) given procarbazine, 12.5 mg/kg i.v. on days --8, --6, and --4, and ATS, 0.6 ml/kg subcutaneously on days --7, --5 and --3, Rejected their grafts, whereas 11 of 15 dogs (73%) not given procarbazine and ATS rejected their grafts (p less than 0.01). Serum lymphocytotoxic antibodies, peripheral leukocyte migration inhibition, and in vivo donor platelet recovery and survival were studied in those recipients receiving six weekly transfusions and in 18 other recipients receiving a single donor transfusion 3 months before marrow grafting. No significant correlation was found among these in vitro and in vivo tests of sensitization. Sensitization to marrow grafts was not reliably detected by the presence of cytotoxic antibodies or leukocyte migration inhibition. Platelet survival, however, was positively correlated with the results of marrow grafting in 12 of 15 (80%) evaluable recipients (p approximately 0.15).", "contents": "Effect of six weekly transfusions on canine marrow grafts: tests for sensitization and abrogation of sensitization by procarbazine and antithymocyte serum. We have previously shown that blood transfusions can immunize a dog and lead to rejection of a subsequent marrow graft despite lethal total body irradiation (TBI). Sensitization to histocompatibility antigens induced by two prior transfusions of whole blood could be overcome by a regimen of procarbazine and anti-thymocyte serum (ATS) preceding TBI. The current study investigated a) whether this regimen could abrogate sensitization induced by six weekly transfusions given from days --50 to --15 preceding a marrow graft, and b) whether platelet survival studies and two in vitro tests of immunity could predict marrow graft rejection. All donor-recipient pairs were histoincompatible, unrelated, and of different breed. Twenty-two recipients received platelet concentrate transfusions and eight received whole blood transfusions. Recipients were given 1200 R TBI and a graft of marrow and peripheral blood leukocytes from the transfusion donor on day 0. Three of 15 recipients (20%) given procarbazine, 12.5 mg/kg i.v. on days --8, --6, and --4, and ATS, 0.6 ml/kg subcutaneously on days --7, --5 and --3, Rejected their grafts, whereas 11 of 15 dogs (73%) not given procarbazine and ATS rejected their grafts (p less than 0.01). Serum lymphocytotoxic antibodies, peripheral leukocyte migration inhibition, and in vivo donor platelet recovery and survival were studied in those recipients receiving six weekly transfusions and in 18 other recipients receiving a single donor transfusion 3 months before marrow grafting. No significant correlation was found among these in vitro and in vivo tests of sensitization. Sensitization to marrow grafts was not reliably detected by the presence of cytotoxic antibodies or leukocyte migration inhibition. Platelet survival, however, was positively correlated with the results of marrow grafting in 12 of 15 (80%) evaluable recipients (p approximately 0.15)."}
{"id": "PMID:6594", "title": "Fine structure of three different anti-fluorescein combining sites: induced circular dichroism of hapten bound to autologous and heterologous recombinants.", "content": "We have previously reported the sequential appearance in hyperimmunized rabbits of three distinct types of antifluorescein-combining sites that can be distinguished by the characteristic induced circular dichroism (CD) of the bound hapten, fluorescein. Such induced CD depends on the configuration of the surrounding residues, and, in the case of anti-fluorescein, can be localized to the configuration of the sub-site which binds the hydroxyxanthenone moiety of fluorescein. In the present investigation, we have studied the fine structure of both autologous and heterologous recombinant sites and of the free chains by measuring the induced CD of bound hapten. Heavy chain dimers at pH 5.4 bound fluorescein that displayed a weak negative CD band which is different from that observed in any of the native antibodies. No induced CD was observed with light chains. Thus, the hydroxyxanthenone subsite does not exist intact in any of the isolated chains. Fluorescein bound to purified autologous recombinants, when studied at pH 7.5, exhibited CD spectra very similar to those observed for the original antibodies. Most significantly, fluorescein bound to purified heterologous recombinants, prepared in all possible combinations, showed CD spectra most similar to those exhibited by sites from which the heavy chain was derived. Thus, the microenvironment of the subsite appears to be due primarily to the heavy chain.", "contents": "Fine structure of three different anti-fluorescein combining sites: induced circular dichroism of hapten bound to autologous and heterologous recombinants. We have previously reported the sequential appearance in hyperimmunized rabbits of three distinct types of antifluorescein-combining sites that can be distinguished by the characteristic induced circular dichroism (CD) of the bound hapten, fluorescein. Such induced CD depends on the configuration of the surrounding residues, and, in the case of anti-fluorescein, can be localized to the configuration of the sub-site which binds the hydroxyxanthenone moiety of fluorescein. In the present investigation, we have studied the fine structure of both autologous and heterologous recombinant sites and of the free chains by measuring the induced CD of bound hapten. Heavy chain dimers at pH 5.4 bound fluorescein that displayed a weak negative CD band which is different from that observed in any of the native antibodies. No induced CD was observed with light chains. Thus, the hydroxyxanthenone subsite does not exist intact in any of the isolated chains. Fluorescein bound to purified autologous recombinants, when studied at pH 7.5, exhibited CD spectra very similar to those observed for the original antibodies. Most significantly, fluorescein bound to purified heterologous recombinants, prepared in all possible combinations, showed CD spectra most similar to those exhibited by sites from which the heavy chain was derived. Thus, the microenvironment of the subsite appears to be due primarily to the heavy chain."}
{"id": "PMID:6595", "title": "Biological expressions of lymphocyte activation. V. Characterization of a soluble immune response suppressor (SIRS) produced by concanavalin A-activated spleen cells.", "content": "Supernatant fluids from murine spleen cell cultures incubated with concanavalin A for 48 hr contain a factor(s), soluble immune response suppressor (SIRS), which suppresses plaque-forming cell responses to sheep erythrocytes by murine spleen cells in vitro. In the present studies, some of the biochemical and biophysical properties of SIRS were investigated. SIRS was non-dialysable; the suppressive activity was stable at 56 degrees C for 30 min, but was destroyed by treatment at 70 degrees C for 30 min, 80 degrees C for 10 min, or at pH 2. The suppressive activity was not absorbed by the stimulating antigen, SRBC, or antisera against murine IgG or mu-chain, suggesting that SIRS does not contain immunoglobulin determinants. Murine spleen and thymus, but not kidney cells, however, absorbed SIRS activity. Enzyme treatments revealed that SIRS was resistant to DNase and RNase, but was destroyed by trypsin and chymotrypsin. In gel filtration with Sephadex G-100, SIRS activity eluted in the fraction corresponding to m.w. in the range between 48,000 and 67,000. With polyacrylamide gel electrophoresis, SIRS activity migrated in the region cathodal to albumin. Isopycnic centrifugation in a cesium chloride gradient suggested that SIRS is a glycoprotein. These supernatant fluids with SIRS activity were also found to contain macrophage migration inhibitory factor (MIF). In the experiments using gel filtration, polyacrylamide gel electrophoresis, and isopycnic centrifugation to fractionate supernatant fluids, SIRS and MIF activity were found in the same fractions, and to date we have been unable to dissociate definitively SIRS activity from MIF activity.", "contents": "Biological expressions of lymphocyte activation. V. Characterization of a soluble immune response suppressor (SIRS) produced by concanavalin A-activated spleen cells. Supernatant fluids from murine spleen cell cultures incubated with concanavalin A for 48 hr contain a factor(s), soluble immune response suppressor (SIRS), which suppresses plaque-forming cell responses to sheep erythrocytes by murine spleen cells in vitro. In the present studies, some of the biochemical and biophysical properties of SIRS were investigated. SIRS was non-dialysable; the suppressive activity was stable at 56 degrees C for 30 min, but was destroyed by treatment at 70 degrees C for 30 min, 80 degrees C for 10 min, or at pH 2. The suppressive activity was not absorbed by the stimulating antigen, SRBC, or antisera against murine IgG or mu-chain, suggesting that SIRS does not contain immunoglobulin determinants. Murine spleen and thymus, but not kidney cells, however, absorbed SIRS activity. Enzyme treatments revealed that SIRS was resistant to DNase and RNase, but was destroyed by trypsin and chymotrypsin. In gel filtration with Sephadex G-100, SIRS activity eluted in the fraction corresponding to m.w. in the range between 48,000 and 67,000. With polyacrylamide gel electrophoresis, SIRS activity migrated in the region cathodal to albumin. Isopycnic centrifugation in a cesium chloride gradient suggested that SIRS is a glycoprotein. These supernatant fluids with SIRS activity were also found to contain macrophage migration inhibitory factor (MIF). In the experiments using gel filtration, polyacrylamide gel electrophoresis, and isopycnic centrifugation to fractionate supernatant fluids, SIRS and MIF activity were found in the same fractions, and to date we have been unable to dissociate definitively SIRS activity from MIF activity."}
{"id": "PMID:6597", "title": "Two distinct cellular patterns in cutaneous necrotizing angiitis.", "content": "Two distinct cellular patterns of necrotizing angiitis involving venules in skin of patients with clinically identical cutaneous lesions were appreciated by the 1 -mum-thick section technique. In those individuals with serum hypocomplementemia, there was a perivenular inflitrate composed predominantly of neutrophils with fibrin deposition and nuclear debris. In patients with normal serum complement levels, in addition to an infiltrate of neutrophils and fibrin deposition, perivenular lymphocytes in various stages of activation were prominent. In both patterns the venules and not the arterioles were affected, mast cells exhibited various degrees of hypogranulation, and basophils and eosinophils were recognized only rarely. Lesions of different clinical age obtained from one hypocomplelmentemic patient and one normocomplementemic patient exhibited consistent cellular patterns, as did a single crop of lesions biopsied twice, 24 hr apart, in a patient with hypocomplementemia. No patient with hypocomplementemia became normocomplementemic or vice versa with persistence of lesions.", "contents": "Two distinct cellular patterns in cutaneous necrotizing angiitis. Two distinct cellular patterns of necrotizing angiitis involving venules in skin of patients with clinically identical cutaneous lesions were appreciated by the 1 -mum-thick section technique. In those individuals with serum hypocomplementemia, there was a perivenular inflitrate composed predominantly of neutrophils with fibrin deposition and nuclear debris. In patients with normal serum complement levels, in addition to an infiltrate of neutrophils and fibrin deposition, perivenular lymphocytes in various stages of activation were prominent. In both patterns the venules and not the arterioles were affected, mast cells exhibited various degrees of hypogranulation, and basophils and eosinophils were recognized only rarely. Lesions of different clinical age obtained from one hypocomplelmentemic patient and one normocomplementemic patient exhibited consistent cellular patterns, as did a single crop of lesions biopsied twice, 24 hr apart, in a patient with hypocomplementemia. No patient with hypocomplementemia became normocomplementemic or vice versa with persistence of lesions."}
{"id": "PMID:6598", "title": "Effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate on genital lesions and encephalitis induced by Herpesvirus hominis type 2 in female mice.", "content": "9-beta-D-Arabinofuranosylhypoxanthine 5'-monophosphate, administered orally or topically, increased the number of survivors and mean day of death in mice inoculated intravaginally with Herpesvirus hominis type 2. Topical application of the drug in ointment significantly reduced the severity of genital lesions. Orally administered drug did not appreciably reduce genital lesions, but it did cause significant increases in the number of survivors and mean day of death, even when administration was started as late as three days after inoculation of virus. Drug applied both topically and orally was more effective than drug applied by either route along. For topical application an ointment was found to be a better vehicle than polyvinyl alcohol or dimethysulfoxide. In some circumstances the vehicle of drug administration itself had some efficacy.", "contents": "Effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate on genital lesions and encephalitis induced by Herpesvirus hominis type 2 in female mice. 9-beta-D-Arabinofuranosylhypoxanthine 5'-monophosphate, administered orally or topically, increased the number of survivors and mean day of death in mice inoculated intravaginally with Herpesvirus hominis type 2. Topical application of the drug in ointment significantly reduced the severity of genital lesions. Orally administered drug did not appreciably reduce genital lesions, but it did cause significant increases in the number of survivors and mean day of death, even when administration was started as late as three days after inoculation of virus. Drug applied both topically and orally was more effective than drug applied by either route along. For topical application an ointment was found to be a better vehicle than polyvinyl alcohol or dimethysulfoxide. In some circumstances the vehicle of drug administration itself had some efficacy."}
{"id": "PMID:6600", "title": "Histamine metabolism. I. Thin-layer radiochromatographic assays for histaminase and histidine decarboxylase enzyme activities.", "content": "Thin-layer radiochromatographic methods for the measurement of histaminase and histidine decarboxylase activities have been developed. The assays are specific for the respective enzymes, are sensitive and reproducible, and can be performed using commercially available substrates. The histaminase assay permits determination of enzyme activity from 2.5 mul of pregnancy sera, 1-2 X 10(6) human granulocytes, and microgram quantities of partially purified human placenta histaminase with an error of less than 5 per cent. The histidine decarboxylase assay permits measurement of nanogram quantities of newly formed histamine from as few as 2 X 10(4) rat peritoneal mast cells or rat basophilic leukemia cells with an error of less than 5 per cent.", "contents": "Histamine metabolism. I. Thin-layer radiochromatographic assays for histaminase and histidine decarboxylase enzyme activities. Thin-layer radiochromatographic methods for the measurement of histaminase and histidine decarboxylase activities have been developed. The assays are specific for the respective enzymes, are sensitive and reproducible, and can be performed using commercially available substrates. The histaminase assay permits determination of enzyme activity from 2.5 mul of pregnancy sera, 1-2 X 10(6) human granulocytes, and microgram quantities of partially purified human placenta histaminase with an error of less than 5 per cent. The histidine decarboxylase assay permits measurement of nanogram quantities of newly formed histamine from as few as 2 X 10(4) rat peritoneal mast cells or rat basophilic leukemia cells with an error of less than 5 per cent."}
{"id": "PMID:6601", "title": "Effect of insulin on mitochondrial oxidative phosphorylation and energy charge of the perfused guinea pig liver.", "content": "The effect of insulin was investigated in the isolated guinea pig liver perfused with Krebs-Ringer bicarbonate buffer containing red blood cells and albumin. In the mitochondria isolated from livers perfused with 10 units of insulin per hour, the phosphorylative activity with glutamate as a substrate increased to about 160 per cent of control 60 minutes after the beginning of perfusion (p less than 0.01). Such an enhanced phosphorylative activity was accompanied by increases in the respiratory control ratio, state 3 respiration, and P/O ratio. On the other hand, in the liver perfused with insulin, the levels of the energy charge and adenine nucleotide quotient increased to a significant degree as compared to the liver without insulin (p less than 0.01 and p less than 0.05, respectively). It is suggested that insulin plays an important role as a portal factor in regulating mitochondrial oxidative phosphorylation and the levels of the phosphorylated adenine nucleotides.", "contents": "Effect of insulin on mitochondrial oxidative phosphorylation and energy charge of the perfused guinea pig liver. The effect of insulin was investigated in the isolated guinea pig liver perfused with Krebs-Ringer bicarbonate buffer containing red blood cells and albumin. In the mitochondria isolated from livers perfused with 10 units of insulin per hour, the phosphorylative activity with glutamate as a substrate increased to about 160 per cent of control 60 minutes after the beginning of perfusion (p less than 0.01). Such an enhanced phosphorylative activity was accompanied by increases in the respiratory control ratio, state 3 respiration, and P/O ratio. On the other hand, in the liver perfused with insulin, the levels of the energy charge and adenine nucleotide quotient increased to a significant degree as compared to the liver without insulin (p less than 0.01 and p less than 0.05, respectively). It is suggested that insulin plays an important role as a portal factor in regulating mitochondrial oxidative phosphorylation and the levels of the phosphorylated adenine nucleotides."}
{"id": "PMID:6603", "title": "The use of phospholipid vesicles for in vitro studies on cholesteryl ester hydrolysis.", "content": "Radiolabeled cholesteryl oleate was incorporated into vesicles prepared from egg yolk lecithin and utilized as a substrate for studies of sterol ester hydrolases present in rat liver homogenates. The cholesteryl oleate was shown to be associated with vesicles (unilamellar liposomes) using Sepharose 4B chromatography. With this substrate, two different cholesteryl ester hydrolytic enzymes were demonstrated in subcellular fractions from the liver homogenates. In the lysosome-rich fraction an acid hydrolase was present, while in the cytosol fraction (150,000 g supernatant), hydrolytic activity was shown to occur with an optimum pH between 8 and 8.5. The substrate was characterized by Sepharose chromatography both before and after incubation with the liver fraction and was not dramatically altered even by rigorous incubation conditions. The lysosomal enzyme preparation was capable of hydrolyzing almost all the cholesteryl oleate in the vesicles. Hydrolysis of the phospholipid was proportionately much less than that of the cholesteryl oleate. Comparisons were performed between the vesicle preparation and an alternate substrate preparation involving the direct addition of cholesteryl oleate in acetone solution. The vesicles appeared to be a better substrate for the lysosomal enzyme whereas the activity in the cytosol fraction did not distinguish between the two substrate preparations. Unsonicated suspensions of cholesteryl oleate and lecithin did not serve as suitable substrates for the enzymes. These studies demonstrate the applicability of cholesteryl ester-containing vesicles as a useful substrate for studying cholesteryl ester hydrolysis in vitro.", "contents": "The use of phospholipid vesicles for in vitro studies on cholesteryl ester hydrolysis. Radiolabeled cholesteryl oleate was incorporated into vesicles prepared from egg yolk lecithin and utilized as a substrate for studies of sterol ester hydrolases present in rat liver homogenates. The cholesteryl oleate was shown to be associated with vesicles (unilamellar liposomes) using Sepharose 4B chromatography. With this substrate, two different cholesteryl ester hydrolytic enzymes were demonstrated in subcellular fractions from the liver homogenates. In the lysosome-rich fraction an acid hydrolase was present, while in the cytosol fraction (150,000 g supernatant), hydrolytic activity was shown to occur with an optimum pH between 8 and 8.5. The substrate was characterized by Sepharose chromatography both before and after incubation with the liver fraction and was not dramatically altered even by rigorous incubation conditions. The lysosomal enzyme preparation was capable of hydrolyzing almost all the cholesteryl oleate in the vesicles. Hydrolysis of the phospholipid was proportionately much less than that of the cholesteryl oleate. Comparisons were performed between the vesicle preparation and an alternate substrate preparation involving the direct addition of cholesteryl oleate in acetone solution. The vesicles appeared to be a better substrate for the lysosomal enzyme whereas the activity in the cytosol fraction did not distinguish between the two substrate preparations. Unsonicated suspensions of cholesteryl oleate and lecithin did not serve as suitable substrates for the enzymes. These studies demonstrate the applicability of cholesteryl ester-containing vesicles as a useful substrate for studying cholesteryl ester hydrolysis in vitro."}
{"id": "PMID:6604", "title": "The metabolism of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid into cholic: an enzyme assay using homogenates of human liver.", "content": "An enzyme assay was developed to measure the conversion of the bile acid precursor, 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA), into cholic acid using homogenates of human liver biopsies. The average rate of metabolism of THCA into cholic acid was found to be 3.9 +/- 0.5 (+/- 1 SD) pmoles of cholic acid formed/mg liver/minute in twelve normal liver biopsies. This assay system can be used to determine if the syndrome of neonatal cholestasis associated with a metabolic block in the conversion of THCA into cholic acid is transmitted as a genetic trait.", "contents": "The metabolism of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid into cholic: an enzyme assay using homogenates of human liver. An enzyme assay was developed to measure the conversion of the bile acid precursor, 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA), into cholic acid using homogenates of human liver biopsies. The average rate of metabolism of THCA into cholic acid was found to be 3.9 +/- 0.5 (+/- 1 SD) pmoles of cholic acid formed/mg liver/minute in twelve normal liver biopsies. This assay system can be used to determine if the syndrome of neonatal cholestasis associated with a metabolic block in the conversion of THCA into cholic acid is transmitted as a genetic trait."}
{"id": "PMID:6605", "title": "Improved methods for the study of hepatic HMG CoA reductase: one-step isolation of mevalonolactone and rapid preparation of endoplasmic reticulum.", "content": "Two new methods are described for the study of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. (1) Endoplasmic reticulum was rapidly prepared by diluting a 10,000 g supernatant with buffer containing 8 mM calcium chloride. The yield of protein and the specific activity of HMG CoA reductase in the pellet subsequently obtained by low speed centrifugation were nearly identical to those in the microsomal pellet prepared by ultracentrifugation. This technique may be particularly useful in studies of the rapid, in vitro modulation of the enzyme. (2) Mevalonolactone was extracted into benzene from the HMG CoA reductase assay mixture with an efficiency of 58%. There was less than 1% extraction of HMG CoA, acetoacetate, or beta-hydroxybutyrate. The extracted mevalonolactone was at least 98% pure as judged by thin-layer chromatography with four different solvent systems. These improved methods should significantly aid studies of the physiological importance of HMG CoA reductase.", "contents": "Improved methods for the study of hepatic HMG CoA reductase: one-step isolation of mevalonolactone and rapid preparation of endoplasmic reticulum. Two new methods are described for the study of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. (1) Endoplasmic reticulum was rapidly prepared by diluting a 10,000 g supernatant with buffer containing 8 mM calcium chloride. The yield of protein and the specific activity of HMG CoA reductase in the pellet subsequently obtained by low speed centrifugation were nearly identical to those in the microsomal pellet prepared by ultracentrifugation. This technique may be particularly useful in studies of the rapid, in vitro modulation of the enzyme. (2) Mevalonolactone was extracted into benzene from the HMG CoA reductase assay mixture with an efficiency of 58%. There was less than 1% extraction of HMG CoA, acetoacetate, or beta-hydroxybutyrate. The extracted mevalonolactone was at least 98% pure as judged by thin-layer chromatography with four different solvent systems. These improved methods should significantly aid studies of the physiological importance of HMG CoA reductase."}
{"id": "PMID:6607", "title": "Control of shell settling in the swimming sea anemone Stomphia coccinea.", "content": "1. Electrical activity has been recorded from Stomphia coccinea during the behavioural sequence in which the detached anemone settles on to a Modiolus shell. 2. When a responsive tentacle contacts the shell, a short, complex burst of pulses is elicited. These remain confined to the region of contact. The endodermal slow-conduction system (SS2) then begins to fire repetitively (a typical example is 16 SS2 pulses at a mean interpulse interval of 5 s) until the pedal disc begins to inflate. Shell-tentacle contact is essential for stimulation of SS2 activity. 3. The complete response, apart from local bending of the column, may be reproduced by electrical stimulation of the SS2 alone. As few as 10 stimuli at frequencies between 1 shock/s and 1 shock/10 s are required to elicit the response.", "contents": "Control of shell settling in the swimming sea anemone Stomphia coccinea. 1. Electrical activity has been recorded from Stomphia coccinea during the behavioural sequence in which the detached anemone settles on to a Modiolus shell. 2. When a responsive tentacle contacts the shell, a short, complex burst of pulses is elicited. These remain confined to the region of contact. The endodermal slow-conduction system (SS2) then begins to fire repetitively (a typical example is 16 SS2 pulses at a mean interpulse interval of 5 s) until the pedal disc begins to inflate. Shell-tentacle contact is essential for stimulation of SS2 activity. 3. The complete response, apart from local bending of the column, may be reproduced by electrical stimulation of the SS2 alone. As few as 10 stimuli at frequencies between 1 shock/s and 1 shock/10 s are required to elicit the response."}
{"id": "PMID:6608", "title": "Two slow conduction systems co-ordinate shell-climbing behaviour in the sea anemone Calliactis parasitica.", "content": "1. Pulses in two slow conducting systems, the ectodermal SS 1 and the endodermal SS 2, were recorded during shell-climbing behaviour. The mean pulse interval of SS 1 pulses was 7-4 s and that of SS 2 pulses was 6-4 s. Activity in both systems may arise as a sensory response of tentacles to shell contact, but the SS 1 and SS 2 may not share the same receptors. 2. Electrical stimulation of the SS 1 and SS 2 together, at a frequency of 1 shock every 5 s, elicits shell-climbing behaviour in the absence of a shell. 3. Low-frequency nerve-net activity (about 1 pulse every 15 s) accompanies column bending during both normal and electrically elicited responses. This activity probably arises as a result of column bending and is not due to a sensory response to the shell.", "contents": "Two slow conduction systems co-ordinate shell-climbing behaviour in the sea anemone Calliactis parasitica. 1. Pulses in two slow conducting systems, the ectodermal SS 1 and the endodermal SS 2, were recorded during shell-climbing behaviour. The mean pulse interval of SS 1 pulses was 7-4 s and that of SS 2 pulses was 6-4 s. Activity in both systems may arise as a sensory response of tentacles to shell contact, but the SS 1 and SS 2 may not share the same receptors. 2. Electrical stimulation of the SS 1 and SS 2 together, at a frequency of 1 shock every 5 s, elicits shell-climbing behaviour in the absence of a shell. 3. Low-frequency nerve-net activity (about 1 pulse every 15 s) accompanies column bending during both normal and electrically elicited responses. This activity probably arises as a result of column bending and is not due to a sensory response to the shell."}
{"id": "PMID:6609", "title": "Responses of trout gill ion transport systems to acute acidosis.", "content": "The response of rainbow trout Na+ and Cl- uptake systems to acute acidosis was tested by slow infusion of lactic acid into anaesthetized animals. Depression of blood pH by 0-4 pH unit had no effect on influx rates for either ion, and we conclude that gill ion uptake systems do not respond rapidly to blood pH changes.", "contents": "Responses of trout gill ion transport systems to acute acidosis. The response of rainbow trout Na+ and Cl- uptake systems to acute acidosis was tested by slow infusion of lactic acid into anaesthetized animals. Depression of blood pH by 0-4 pH unit had no effect on influx rates for either ion, and we conclude that gill ion uptake systems do not respond rapidly to blood pH changes."}
{"id": "PMID:6610", "title": "On the interaction of NH+4 and Na+ fluxes in the isolated trout gill.", "content": "1. Sodium influx was measured in isolated, previously perfused gill arches of rainbow trout, Salmo gairdneri, by measuring incorporation of 22Na into gill tissue following timed exposure to a 1 mM 22NaCl medium. Transport rates approximated those estimated for intact fish and were linear for at least one min. 2. NH4Cl-containing perfusates at pH 7 and 8 stimulated Na+ influx equally, indicating that only ionized ammonia is important in the transport process. A Na+/NH4+ exchange at basal and/or lateral membranes of the transporting cells is suggested. 3. Low-sodium Ringer perfusate augmented Na+ influx; in one group of gills the transport rate was more than double that of NaCl Ringer controls. The increase in transport induced by internal NH4+ was not additive with the low sodium augmentation. A reduction in intracellular (Na+) is postulated as the mechanism operating in both cases. 4. Ouabain had no appreciable effect on Na+ influx, either with or without NH4+ in the perfusate. Diamox partially blocked the augmented Na+ influx induced by NH4+. Amiloride completely inhibited Na+ influx, both with and without NH4+ in the perfusate.", "contents": "On the interaction of NH+4 and Na+ fluxes in the isolated trout gill. 1. Sodium influx was measured in isolated, previously perfused gill arches of rainbow trout, Salmo gairdneri, by measuring incorporation of 22Na into gill tissue following timed exposure to a 1 mM 22NaCl medium. Transport rates approximated those estimated for intact fish and were linear for at least one min. 2. NH4Cl-containing perfusates at pH 7 and 8 stimulated Na+ influx equally, indicating that only ionized ammonia is important in the transport process. A Na+/NH4+ exchange at basal and/or lateral membranes of the transporting cells is suggested. 3. Low-sodium Ringer perfusate augmented Na+ influx; in one group of gills the transport rate was more than double that of NaCl Ringer controls. The increase in transport induced by internal NH4+ was not additive with the low sodium augmentation. A reduction in intracellular (Na+) is postulated as the mechanism operating in both cases. 4. Ouabain had no appreciable effect on Na+ influx, either with or without NH4+ in the perfusate. Diamox partially blocked the augmented Na+ influx induced by NH4+. Amiloride completely inhibited Na+ influx, both with and without NH4+ in the perfusate."}
{"id": "PMID:6611", "title": "The mobilization of calcium and bicarbonate by raised concentrations of potassium in the haemolymph of the snail, Helix pomatia.", "content": "1. After the concentration of potassium in the haemolymph of Helix pomatia has been raised by the infusion of KCl, it falls approximately exponentially for a time and then tends to rise. The accompanying rise and fall of calcium concentration can be fitted to a simple mathematical model. 2. The mobilization of calcium is accompanied by the generation of bicarbonate in equivalent amounts, without much change in pH or Pco2. 3. There is probably an increased production or retention of carbon dioxide at this time, but the main cause of the changes in calcium and bicarbonate is not respiratory acidosis. 4. The concentration of potassium rises in snalis that have been infused with CaCl2. 5. The adverse responses visible in snails infused with KCl are largely prevented when CaCl2 is infused at the same time. 6. Homeostasis seems to involve the maintenance of a proper balance of calcium and potassium concentrations.", "contents": "The mobilization of calcium and bicarbonate by raised concentrations of potassium in the haemolymph of the snail, Helix pomatia. 1. After the concentration of potassium in the haemolymph of Helix pomatia has been raised by the infusion of KCl, it falls approximately exponentially for a time and then tends to rise. The accompanying rise and fall of calcium concentration can be fitted to a simple mathematical model. 2. The mobilization of calcium is accompanied by the generation of bicarbonate in equivalent amounts, without much change in pH or Pco2. 3. There is probably an increased production or retention of carbon dioxide at this time, but the main cause of the changes in calcium and bicarbonate is not respiratory acidosis. 4. The concentration of potassium rises in snalis that have been infused with CaCl2. 5. The adverse responses visible in snails infused with KCl are largely prevented when CaCl2 is infused at the same time. 6. Homeostasis seems to involve the maintenance of a proper balance of calcium and potassium concentrations."}
{"id": "PMID:6612", "title": "A study of the unidirectional fluxes of Na and Cl across the gills of the dogfish Scyliorhinus canicula (Chondrichthyes).", "content": "The gills of the dogfish Scyliorhinus canicula are more permeable to Cl than to Na. In sea water, influx of Na and Cl exceeded the efflux of these ions. Under these conditions the fish were slightly electronegative, by about 2 mV, to the external solution. The net accumulation of Cl could be accounted for by diffusion along the observed electrochemical gradient byt the movement of Na into the fish was more consistent with an electrically neutral active Na transport mechanism (using the Ussing flux ratio criterion). When the external pH was was changed from 7-8 to 6-9,, influxes of Na and Cl were depressed, while the effluxes were unaffected, and the fish became slightly less electronegative. In artificial solutions, in which the concentrations of Na and Cl were lowered and replaced with urea to maintain the total osmotic concentration, Na influx displayed saturation kinetics, while Na efflux increased with decreasing Na concentrations. Cl influx decreased linearly, while Cl efflux remained constant. The efflux of Cl could not be reconciled with a process of passive diffusion along any of the observed electrochemical gradients and thus could reflect the presence of an active transport mechanism.", "contents": "A study of the unidirectional fluxes of Na and Cl across the gills of the dogfish Scyliorhinus canicula (Chondrichthyes). The gills of the dogfish Scyliorhinus canicula are more permeable to Cl than to Na. In sea water, influx of Na and Cl exceeded the efflux of these ions. Under these conditions the fish were slightly electronegative, by about 2 mV, to the external solution. The net accumulation of Cl could be accounted for by diffusion along the observed electrochemical gradient byt the movement of Na into the fish was more consistent with an electrically neutral active Na transport mechanism (using the Ussing flux ratio criterion). When the external pH was was changed from 7-8 to 6-9,, influxes of Na and Cl were depressed, while the effluxes were unaffected, and the fish became slightly less electronegative. In artificial solutions, in which the concentrations of Na and Cl were lowered and replaced with urea to maintain the total osmotic concentration, Na influx displayed saturation kinetics, while Na efflux increased with decreasing Na concentrations. Cl influx decreased linearly, while Cl efflux remained constant. The efflux of Cl could not be reconciled with a process of passive diffusion along any of the observed electrochemical gradients and thus could reflect the presence of an active transport mechanism."}
{"id": "PMID:6613", "title": "The actions of some putative neurotransmitters on the cockroach salivary gland.", "content": "1. Certain putative transmitters were applied to the innervated cockroach salivary gland and their effects on the resting potential and the neurally evoked secretory potential of the acinar cells were observed. 2. gamma-Aminobutyric acid, glutamate, glycine, aspartate and alanine had no significant effect on the resting potential. However, gamma-aminobutyric acid and glutamate reduced the neurally evoked secretory potential but only at concentrations above 10(-3) M3. Acetylcholine and carbachol appeared to act by modifying transmitter output from the salivary nerves. These substances failed to have any effect on the resting potential. 4. The biogenic amines, adrenaline, dopamine, noradrenaline, 5-hydroxy-tryptamine and octopamine, produced hyperpolarizing responses, graded according to concentration. 5. It is suggested that dopamine, the most potent of the biogenic amines tested, is the transmitter at this junction.", "contents": "The actions of some putative neurotransmitters on the cockroach salivary gland. 1. Certain putative transmitters were applied to the innervated cockroach salivary gland and their effects on the resting potential and the neurally evoked secretory potential of the acinar cells were observed. 2. gamma-Aminobutyric acid, glutamate, glycine, aspartate and alanine had no significant effect on the resting potential. However, gamma-aminobutyric acid and glutamate reduced the neurally evoked secretory potential but only at concentrations above 10(-3) M3. Acetylcholine and carbachol appeared to act by modifying transmitter output from the salivary nerves. These substances failed to have any effect on the resting potential. 4. The biogenic amines, adrenaline, dopamine, noradrenaline, 5-hydroxy-tryptamine and octopamine, produced hyperpolarizing responses, graded according to concentration. 5. It is suggested that dopamine, the most potent of the biogenic amines tested, is the transmitter at this junction."}
{"id": "PMID:6614", "title": "Branchial ion uptake in arctic grayling: resting values and effects of acid-base disturbance.", "content": "1. Techniques for the measurement of unidirectional flux rates in fish which require no anaesthesia or surgery are described. 2. Resting values for Cl- uptake at 10 and 17 degrees C were 8-03 +/- 1-11 and 13-52 +/- 0-95 mu-equiv. 200 g-1 h-1 (+/- S.E.), respectively; and for Na+ the rates were 15-49 +/- 0-40 and 26-30 +/- 0-36, respectively. 3. Hypercapnic acidosis caused an increase in Na+ uptake, presumably through Na+/H+ (or NH+4) exchange. It is suggested that this is a compensation mechanism leading to the increase in blood buffering observed in response to hypercapnia. 4. Alkalosis was observed following acute temperature increase and was accompanied by an increase in the rate of Cl-/HCO-3 exchange and also by an increase in Na+/H+ exchange. 5. The role of these branchial ion exchange mechanisms in overall acidbase regulation is discussed.", "contents": "Branchial ion uptake in arctic grayling: resting values and effects of acid-base disturbance. 1. Techniques for the measurement of unidirectional flux rates in fish which require no anaesthesia or surgery are described. 2. Resting values for Cl- uptake at 10 and 17 degrees C were 8-03 +/- 1-11 and 13-52 +/- 0-95 mu-equiv. 200 g-1 h-1 (+/- S.E.), respectively; and for Na+ the rates were 15-49 +/- 0-40 and 26-30 +/- 0-36, respectively. 3. Hypercapnic acidosis caused an increase in Na+ uptake, presumably through Na+/H+ (or NH+4) exchange. It is suggested that this is a compensation mechanism leading to the increase in blood buffering observed in response to hypercapnia. 4. Alkalosis was observed following acute temperature increase and was accompanied by an increase in the rate of Cl-/HCO-3 exchange and also by an increase in Na+/H+ exchange. 5. The role of these branchial ion exchange mechanisms in overall acidbase regulation is discussed."}
{"id": "PMID:6615", "title": "[Characterization of the oxidoreductase inhibitor (author's transl)].", "content": "The oxidoreductase inhibitor was prepared from NAD in alkaline solution, and purified chromatographically. Investigations are reported on the extinction and fluorescence spectra, stability of the inhibitor, and the dependence of inhibition on the concentration of enzyme and coenzyme. Kinetic studies show that the inhibition is non-competitive.", "contents": "[Characterization of the oxidoreductase inhibitor (author's transl)]. The oxidoreductase inhibitor was prepared from NAD in alkaline solution, and purified chromatographically. Investigations are reported on the extinction and fluorescence spectra, stability of the inhibitor, and the dependence of inhibition on the concentration of enzyme and coenzyme. Kinetic studies show that the inhibition is non-competitive."}
{"id": "PMID:6616", "title": "[Formation and purification of the oxidoreductase inhibitor from NAD (AUTHOR'S TRANSL)].", "content": "The oxidoreductase inhibitor is not formed from NADH as previously thought, but only from NAD under alkaline conditions. Analogues of NAD (e.g. NADP) and components of the NAD molecule (e.g. ADP) have no effect on the formation of the inhibitor. The most favourable pH, temperature, duration of incubation, type of buffer and NAD concentration for the formation of the inhibitor were investigated. The method for the formation and chromatographic isolation of the oxidoreductase inhibitor is briefly described.", "contents": "[Formation and purification of the oxidoreductase inhibitor from NAD (AUTHOR'S TRANSL)]. The oxidoreductase inhibitor is not formed from NADH as previously thought, but only from NAD under alkaline conditions. Analogues of NAD (e.g. NADP) and components of the NAD molecule (e.g. ADP) have no effect on the formation of the inhibitor. The most favourable pH, temperature, duration of incubation, type of buffer and NAD concentration for the formation of the inhibitor were investigated. The method for the formation and chromatographic isolation of the oxidoreductase inhibitor is briefly described."}
{"id": "PMID:6617", "title": "Ventilation and metabolic rate of young rainbow trout (Salmo gairdneri) exposed to sublethal environmental pH.", "content": "Differences between ventilatory response and metabolic rates of young rainbow trout tested within the sublethal range of pH 6 to pH 9 were observed using a flowing water respirometer. The oxygen consumption was monitored at swimming speeds of 12 cm/sec and 24 cm/sec. The oxygen consumption rates at 24 cm/sec and pH 6 (423 mg/kg-hr) and pH 9 (367 mg/kg-hr) were considerably higher than those determined near neutrality (328 mg/kg-hr). Ventilation rate increased to either side of neutrality, but significantly fewer respiratory reversals, or \"coughs,\" were observed at pH 6 and a greater number at pH 9 than occurred at pH 7 and 8 or in untested fish. The respiratory-cough response is shown to be pH-dependent in rainbow trout and may therefore not be as reliable an indication of pollutant-caused stress in studies where the experimental pH has not been specified or controlled.", "contents": "Ventilation and metabolic rate of young rainbow trout (Salmo gairdneri) exposed to sublethal environmental pH. Differences between ventilatory response and metabolic rates of young rainbow trout tested within the sublethal range of pH 6 to pH 9 were observed using a flowing water respirometer. The oxygen consumption was monitored at swimming speeds of 12 cm/sec and 24 cm/sec. The oxygen consumption rates at 24 cm/sec and pH 6 (423 mg/kg-hr) and pH 9 (367 mg/kg-hr) were considerably higher than those determined near neutrality (328 mg/kg-hr). Ventilation rate increased to either side of neutrality, but significantly fewer respiratory reversals, or \"coughs,\" were observed at pH 6 and a greater number at pH 9 than occurred at pH 7 and 8 or in untested fish. The respiratory-cough response is shown to be pH-dependent in rainbow trout and may therefore not be as reliable an indication of pollutant-caused stress in studies where the experimental pH has not been specified or controlled."}
{"id": "PMID:6618", "title": "Gustatory hairs on the mosquito, Culiseta inornata.", "content": "Gustatory hairs were investigated on the legs and mouthparts of Culiseta inornata (Williston) (Diptera: Culicidae). One type of hair, each innervated by four neurons, was found on the legs. Two of the neurons responded to NaCl stimulation, one neuron to water stimulation, and one neuron to sucrose stimulation. Three kinds of hairs designated Type I (T1), Type 2 (T2) and Type 3 (T3) were analyzed on the labella. The T1 hairs are innervated by one sugar neuron, one mechanoreceptor, two salt neurons and one water neuron. The T2 hairs are innervated by two salt neurons and one mechanoreceptor. The T3 hairs, located on the oral surface of the labella, are innervated by a variable number (2-5) of neurons. Precise identification of the T3 chemosensory neurons was not made because of the small size and inaccessibility of the T3 hairs. Chemosensory hairs on the tip of the labrum were tested electrophysiologically. the sequence of decreasing effeectiveness for the three salts tested was KCl greater than NaCl greater than LiCl. Labral chemoreceptors also responded positively to sucrose.", "contents": "Gustatory hairs on the mosquito, Culiseta inornata. Gustatory hairs were investigated on the legs and mouthparts of Culiseta inornata (Williston) (Diptera: Culicidae). One type of hair, each innervated by four neurons, was found on the legs. Two of the neurons responded to NaCl stimulation, one neuron to water stimulation, and one neuron to sucrose stimulation. Three kinds of hairs designated Type I (T1), Type 2 (T2) and Type 3 (T3) were analyzed on the labella. The T1 hairs are innervated by one sugar neuron, one mechanoreceptor, two salt neurons and one water neuron. The T2 hairs are innervated by two salt neurons and one mechanoreceptor. The T3 hairs, located on the oral surface of the labella, are innervated by a variable number (2-5) of neurons. Precise identification of the T3 chemosensory neurons was not made because of the small size and inaccessibility of the T3 hairs. Chemosensory hairs on the tip of the labrum were tested electrophysiologically. the sequence of decreasing effeectiveness for the three salts tested was KCl greater than NaCl greater than LiCl. Labral chemoreceptors also responded positively to sucrose."}
{"id": "PMID:6619", "title": "Proton transport by phosphate diffusion--a mechanism of facilitated CO2 transfer.", "content": "We have measured CO2 fluxes across phosphate solutions at different carbonic anhydrase concentrations, bicarbonate concentration gradients, phosphate concentrations, and mobilities. Temperature was 22-25 degrees C, the pH of the phosphate solutions was 7.0-7.3. We found that under physiological conditions of pH and pCO2 a facilitated diffusion of CO2 occurs in addition to free diffusion when (a) sufficient carbonic anhydrase is present, and (b) a concentration gradient of HCO3- is established along with a pCO2 gradient, and (c) the phosphate buffer has a mobility comparable to that of bicarbonate. When the phosphate was immobilized by attaching 0.25-mm-long cellulose particles, no facilitation of CO2 diffusion was detectable. A mechanism of facilitated CO2 diffusion in phosphate solutions analogous to that in albumin solutions was proposed on the basis of these findings: bicarbonate diffusion together with a facilitated proton transport by phosphate diffusion. A mathematical model of this mechanism was formulated. The CO2 fluxed predicted by the model agree quantitatively with the experimentally determined fluxes. It is concluded that a highly effective proton transport mechanism acts in solutions of mobile phosphate buffers. By this mechanism; CO2 transfer may be increased up to fivefold and proton transfer may be increased to 10,000-fold.", "contents": "Proton transport by phosphate diffusion--a mechanism of facilitated CO2 transfer. We have measured CO2 fluxes across phosphate solutions at different carbonic anhydrase concentrations, bicarbonate concentration gradients, phosphate concentrations, and mobilities. Temperature was 22-25 degrees C, the pH of the phosphate solutions was 7.0-7.3. We found that under physiological conditions of pH and pCO2 a facilitated diffusion of CO2 occurs in addition to free diffusion when (a) sufficient carbonic anhydrase is present, and (b) a concentration gradient of HCO3- is established along with a pCO2 gradient, and (c) the phosphate buffer has a mobility comparable to that of bicarbonate. When the phosphate was immobilized by attaching 0.25-mm-long cellulose particles, no facilitation of CO2 diffusion was detectable. A mechanism of facilitated CO2 diffusion in phosphate solutions analogous to that in albumin solutions was proposed on the basis of these findings: bicarbonate diffusion together with a facilitated proton transport by phosphate diffusion. A mathematical model of this mechanism was formulated. The CO2 fluxed predicted by the model agree quantitatively with the experimentally determined fluxes. It is concluded that a highly effective proton transport mechanism acts in solutions of mobile phosphate buffers. By this mechanism; CO2 transfer may be increased up to fivefold and proton transfer may be increased to 10,000-fold."}
{"id": "PMID:6620", "title": "Distribution of rhodopsin and retinochrome in the squid retina.", "content": "The cephalopod retina contains two kinds of photopigments, rhodopsin and retinochrome. For many years retinochrome has been thought to be localized in the inner segments of the visual cells, whereas rhodopsin is in the outer segments. However, it is now clear that retinochrome can be extracted also from fragments of outer segments. In the dark-adapted retina of Loligo pealei retinochrome is distributed half-and-half in the inner and outer segments. Todarodes pacificus contains much more retinochrome than Loligo, and it is more abundant in the outer than in the inner segments. The outer segments of Loligo contain retinochrome and metarhodopsin in addition to rhodopsin, whether squids are kept in the dark or in the light. But there is extremely little metarhodopsin (about 3% of rhodopsin) even in light-adapted eyes. The inner segments contain only retinochrome, and much less in the light than in the dark. On the other hand, retinochrome in the outer segments increases markedly during light adaptation. These facts suggest the possibility that some retinochrome moves forward from the inner to the outer segments during light adaptation and there reacts with metarhodopsin to promote regeneration of rhodopsin.", "contents": "Distribution of rhodopsin and retinochrome in the squid retina. The cephalopod retina contains two kinds of photopigments, rhodopsin and retinochrome. For many years retinochrome has been thought to be localized in the inner segments of the visual cells, whereas rhodopsin is in the outer segments. However, it is now clear that retinochrome can be extracted also from fragments of outer segments. In the dark-adapted retina of Loligo pealei retinochrome is distributed half-and-half in the inner and outer segments. Todarodes pacificus contains much more retinochrome than Loligo, and it is more abundant in the outer than in the inner segments. The outer segments of Loligo contain retinochrome and metarhodopsin in addition to rhodopsin, whether squids are kept in the dark or in the light. But there is extremely little metarhodopsin (about 3% of rhodopsin) even in light-adapted eyes. The inner segments contain only retinochrome, and much less in the light than in the dark. On the other hand, retinochrome in the outer segments increases markedly during light adaptation. These facts suggest the possibility that some retinochrome moves forward from the inner to the outer segments during light adaptation and there reacts with metarhodopsin to promote regeneration of rhodopsin."}
{"id": "PMID:6621", "title": "Formation and isolation of leucocidin from Pseudomonas aeruginosa.", "content": "A toxic substance, which destroyed leucocytes from man but was inactive against erythrocytes, was demonstrated in cultures of four out of 110 strains of Pseudomonas aeruginosa tested. The toxin, designated 'leucocidin', was cell-bound as a precursor toxin, exhibiting little or no toxicity. It was converted into toxin with maximum activity by various proteases including an endogenous elastase. The production of leucocidin was directly proportional to the number of bacteria and was not influenced by variations in media, iron concentration, pH or temperature. The best method for large-scale production of leucocidin was autolysis of washed bacteria.", "contents": "Formation and isolation of leucocidin from Pseudomonas aeruginosa. A toxic substance, which destroyed leucocytes from man but was inactive against erythrocytes, was demonstrated in cultures of four out of 110 strains of Pseudomonas aeruginosa tested. The toxin, designated 'leucocidin', was cell-bound as a precursor toxin, exhibiting little or no toxicity. It was converted into toxin with maximum activity by various proteases including an endogenous elastase. The production of leucocidin was directly proportional to the number of bacteria and was not influenced by variations in media, iron concentration, pH or temperature. The best method for large-scale production of leucocidin was autolysis of washed bacteria."}
{"id": "PMID:6622", "title": "The production and growth characteristics of yeast and mycelial forms of Candida albicans in continuous culture.", "content": "The growth characteristics of Candida albicans CM145,348 have been examined under aerobic conditions in continuous culture. At different steady states the environment was controlled with respect to the concentrations of dissolved oxygen, carbon and nitrogen, the pH, and the temperature. Dry matter, substrate concentration, yield, specific oxygen uptake, specific carbon dioxide release and respiration quotient were examined as a function of the dilution rate. The morphology depended on the carbon source. Maltose produced a mycelial morphology, whereas with lactate a yeast culture was obtained. With fructose or glucose as a carbon source a mixed morphology of yeast, pseudo-mycelial and mycelial forms was produced. A larger number of different growth conditions were examined in batch culture but a mixed morphology was always obtained.", "contents": "The production and growth characteristics of yeast and mycelial forms of Candida albicans in continuous culture. The growth characteristics of Candida albicans CM145,348 have been examined under aerobic conditions in continuous culture. At different steady states the environment was controlled with respect to the concentrations of dissolved oxygen, carbon and nitrogen, the pH, and the temperature. Dry matter, substrate concentration, yield, specific oxygen uptake, specific carbon dioxide release and respiration quotient were examined as a function of the dilution rate. The morphology depended on the carbon source. Maltose produced a mycelial morphology, whereas with lactate a yeast culture was obtained. With fructose or glucose as a carbon source a mixed morphology of yeast, pseudo-mycelial and mycelial forms was produced. A larger number of different growth conditions were examined in batch culture but a mixed morphology was always obtained."}
{"id": "PMID:6623", "title": "The effect of nitrogen limitation on catabolite repression of amidase, histidase and urocanase in Pseudomonas aeruginosa.", "content": "In Pseudomonas aeruginosa, the synthesis of histidase, urocanase and amidase is severly repressed when succinate is added to a culture growing in pyruvate + ammonium salts medium. When growth is nitrogen-limited, catabolite repression by succinate of histidase and urocanase synthesis does not occur but succinate repression of amidase synthesis persists. Amidase synthesis is not regulated in the same way as histidase synthesis by the availability of other nitrogen compounds for growth. Growth of P. aeruginosa strain PACI in succinate + histidine media is nitrogen-limited since this strain is defective in a histidine transport system. When methyl-ammonium chloride is added to succinate + histidine media, growth inhibition occurs. Mutants isolated from succinate + histidine + methylammonium chloride plates were found to be resistant to catabolite repression by succinate even in ammonium salts media. It is suggested that the hut genes of P. aeruginosa may be regulated in the same way as in Klebsiella aerogenes, by induction by urocanate and activation by either the cyclic AMP-dependent activator protein or by glutamine synthetase.", "contents": "The effect of nitrogen limitation on catabolite repression of amidase, histidase and urocanase in Pseudomonas aeruginosa. In Pseudomonas aeruginosa, the synthesis of histidase, urocanase and amidase is severly repressed when succinate is added to a culture growing in pyruvate + ammonium salts medium. When growth is nitrogen-limited, catabolite repression by succinate of histidase and urocanase synthesis does not occur but succinate repression of amidase synthesis persists. Amidase synthesis is not regulated in the same way as histidase synthesis by the availability of other nitrogen compounds for growth. Growth of P. aeruginosa strain PACI in succinate + histidine media is nitrogen-limited since this strain is defective in a histidine transport system. When methyl-ammonium chloride is added to succinate + histidine media, growth inhibition occurs. Mutants isolated from succinate + histidine + methylammonium chloride plates were found to be resistant to catabolite repression by succinate even in ammonium salts media. It is suggested that the hut genes of P. aeruginosa may be regulated in the same way as in Klebsiella aerogenes, by induction by urocanate and activation by either the cyclic AMP-dependent activator protein or by glutamine synthetase."}
{"id": "PMID:6624", "title": "Decreased permeability as a mechanism of resistance to methyl benzimadazol-2-yl carbamate (MBC) in Sporobolomyces roseus.", "content": "Mutants of Sporobolomyces roseus resistant to benzimidazole fungicides varied in their responses to 2-(thiazol-4-yl) benzimidazole (thiabendazole, TBZ), methyl 1-(butylcarbamoyl)-benzimidazol-2-yl carbamate (benomyl) and methyl benzimidazol-2-yl carbamate (carbendazim, MCB). Incorporation of [14C] MBC into trichloroacetic acid extracts of the sensitive strain S4 increased during a 2 h incubation period, whereas incorporation into the resistant mutant M55 was unchanged. [14C] MBC uptake by S4 cells was five times higher than that by M55. MBC was identified as the main radioactive compound inside the S4 cells and reached a level of 2.4 mug/100 mg dry wt. The compound MBC enters the cells of Sp. roseus by a temperature-, energy-, pH- and concentration-dependent transport system which may be specific for compounds containing a benzimidazole nucleus. It is suggested that tolerance of M55 to MBC is due to decreased permeability of the cell to this compound.", "contents": "Decreased permeability as a mechanism of resistance to methyl benzimadazol-2-yl carbamate (MBC) in Sporobolomyces roseus. Mutants of Sporobolomyces roseus resistant to benzimidazole fungicides varied in their responses to 2-(thiazol-4-yl) benzimidazole (thiabendazole, TBZ), methyl 1-(butylcarbamoyl)-benzimidazol-2-yl carbamate (benomyl) and methyl benzimidazol-2-yl carbamate (carbendazim, MCB). Incorporation of [14C] MBC into trichloroacetic acid extracts of the sensitive strain S4 increased during a 2 h incubation period, whereas incorporation into the resistant mutant M55 was unchanged. [14C] MBC uptake by S4 cells was five times higher than that by M55. MBC was identified as the main radioactive compound inside the S4 cells and reached a level of 2.4 mug/100 mg dry wt. The compound MBC enters the cells of Sp. roseus by a temperature-, energy-, pH- and concentration-dependent transport system which may be specific for compounds containing a benzimidazole nucleus. It is suggested that tolerance of M55 to MBC is due to decreased permeability of the cell to this compound."}
{"id": "PMID:6625", "title": "Accumulation and storage of Zn2+ by Candida utilis.", "content": "Starved cells of Candida utilis accumulated Zn2+ by two different processes. The first was a rapid, energy- and temperature-independent system that probably represented binding to the cell surface. The cells also possessed an energy-, pH-, and temperature-dependent system that was capable of accumulating much greater quantities of the cation than the binding process. The energy-dependent system was inhibited by KCN, Na2HAsO4, m-chlorophenyl carbonylcyanide hydrazone, N-ethylmaleimide, EDTA and diethylenetriaminepenta-acetic acid. The system was specific inasmuch as Ca2+, Cr3+, Mn2+, Co2+ or Cu2+ did not compete with, inhibit, or enhance the process, Zn2+ uptake was inhibited by Cd2+. The system exhibited saturation kinetics with a half-saturation value of 1.3 muM and a maximum rate of 0.21 (nmol Zn2+) min(-1) (mg dry wt(-1)) at 30 degrees C. Zn2+ uptake required intact membranes since only the binding process was observed in the presence of nystatin, toluene, or sodium dodecyl sulphate. Cells did not exchange recently accumulated toluene, or sodium dodecyl sulphate. Cells did not exchange recently accumulated 65Zn following the addition of a large excess of non-radioactive Zn2+. Similarly, cells pre-loaded with 65Zn did not lose the cation during starvation, and efflux did not occur when glucose and exogenous Zn2+ were supplied after the starvation period. Efflux was only observed after the addition of toluene or nystatin, or when cells were heated to 100 degrees C. Cells fed a large quantity of Zn2+ contained a protein fraction resembling animal cell metallothionein. In batch culture, cells of C. utilis accumulated Zn2+ only during the lag phase and the latter half of the exponential-growth phase.", "contents": "Accumulation and storage of Zn2+ by Candida utilis. Starved cells of Candida utilis accumulated Zn2+ by two different processes. The first was a rapid, energy- and temperature-independent system that probably represented binding to the cell surface. The cells also possessed an energy-, pH-, and temperature-dependent system that was capable of accumulating much greater quantities of the cation than the binding process. The energy-dependent system was inhibited by KCN, Na2HAsO4, m-chlorophenyl carbonylcyanide hydrazone, N-ethylmaleimide, EDTA and diethylenetriaminepenta-acetic acid. The system was specific inasmuch as Ca2+, Cr3+, Mn2+, Co2+ or Cu2+ did not compete with, inhibit, or enhance the process, Zn2+ uptake was inhibited by Cd2+. The system exhibited saturation kinetics with a half-saturation value of 1.3 muM and a maximum rate of 0.21 (nmol Zn2+) min(-1) (mg dry wt(-1)) at 30 degrees C. Zn2+ uptake required intact membranes since only the binding process was observed in the presence of nystatin, toluene, or sodium dodecyl sulphate. Cells did not exchange recently accumulated toluene, or sodium dodecyl sulphate. Cells did not exchange recently accumulated 65Zn following the addition of a large excess of non-radioactive Zn2+. Similarly, cells pre-loaded with 65Zn did not lose the cation during starvation, and efflux did not occur when glucose and exogenous Zn2+ were supplied after the starvation period. Efflux was only observed after the addition of toluene or nystatin, or when cells were heated to 100 degrees C. Cells fed a large quantity of Zn2+ contained a protein fraction resembling animal cell metallothionein. In batch culture, cells of C. utilis accumulated Zn2+ only during the lag phase and the latter half of the exponential-growth phase."}
{"id": "PMID:6630", "title": "Mortality and cerebral metabolism after bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats.", "content": "Mortality and cerebral glycolytic metabolism were studied after bilateral ligation of the common carotid artery in normotensive Wistar rats (NTR), and spontaneously hypertensive rats (SHR) derived from Wistar strain. In the first 24 hours after occlusion of carotid arteries, 72 per cent of 108 SHR died, whereas it was fatal in only 16 per cent of 43 NTR. In SHR, cerebral lactate and cerebral lactate/pyruvate ratio (L/P ratio) increased by 12.4 and 12.1 times the control, respectively at five to six hours after ligation, and remained raised even in rats surviving for two to three days thereafter. Changes in cerebral lactate and L/P ratio were minimal in NTR. Cerebral ATP decreased markedly at five to six hours after ligation in SHR studied. These results indicate that bilateral carotid artery ligation causes severe brain damage in SHR but not in NTR, suggesting hypertension per se to be operative for the development of cerebral ischaemia.", "contents": "Mortality and cerebral metabolism after bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats. Mortality and cerebral glycolytic metabolism were studied after bilateral ligation of the common carotid artery in normotensive Wistar rats (NTR), and spontaneously hypertensive rats (SHR) derived from Wistar strain. In the first 24 hours after occlusion of carotid arteries, 72 per cent of 108 SHR died, whereas it was fatal in only 16 per cent of 43 NTR. In SHR, cerebral lactate and cerebral lactate/pyruvate ratio (L/P ratio) increased by 12.4 and 12.1 times the control, respectively at five to six hours after ligation, and remained raised even in rats surviving for two to three days thereafter. Changes in cerebral lactate and L/P ratio were minimal in NTR. Cerebral ATP decreased markedly at five to six hours after ligation in SHR studied. These results indicate that bilateral carotid artery ligation causes severe brain damage in SHR but not in NTR, suggesting hypertension per se to be operative for the development of cerebral ischaemia."}
{"id": "PMID:6631", "title": "Effects of two desensitization techniques, biofeedback and relaxation, on intractable epilepsy: follow-up study.", "content": "Two techniques of desedsitization, biofeedback and relaxation, were employed in a crossover design for the treatment of three young female patinets suffering from drug resistant epilepsy associated with anxiety and phobic symptoms. The patients were followed up for 15 months after the six months of treatment. The results indicate that both relaxation and biofeedback improved the patients' control of their seizures and the effects were maintained during the follow-up period.", "contents": "Effects of two desensitization techniques, biofeedback and relaxation, on intractable epilepsy: follow-up study. Two techniques of desedsitization, biofeedback and relaxation, were employed in a crossover design for the treatment of three young female patinets suffering from drug resistant epilepsy associated with anxiety and phobic symptoms. The patients were followed up for 15 months after the six months of treatment. The results indicate that both relaxation and biofeedback improved the patients' control of their seizures and the effects were maintained during the follow-up period."}
{"id": "PMID:6632", "title": "Skeletal muscle necrosis following membrane-active drugs plus serotonin.", "content": "Administration of imipramine plus serotonin (5-HT) to rats has been proposed as an animal model of Duchenne muscular dystrophy. We studied the skeletal muscle necrosis produced in male rats given 5-HT after pretreatment with imipramine, other tricyclic antidepressants, or antihistamines, which like the tricyclic antidepressants, can block neuronal reuptake of 5-HT. Following one of these agents plus 5-HT, 20 mg/kg subcutaneously (s.c.), necrosis was more severe in the soleus muscle than the quadriceps. There was no significant difference in the incidence of necrosis in the soleus and quadriceps muscles following one of these agents plus 5-HT, 100 mg/kg, intraperitoneally (i.p.). After one of these agents plus 5-HT i.p., but not 5-HT s.c., extensive necrosis was significantly more frequent and severe in the quadriceps muscle than after 5-HT s.c. Chlorpheniramine (CP) plus 5-HT, 2.5 mg/kg intravenously, produced less muscle necrosis than CP plus 5-HT s.c. or i.p. The necrosis produced by CP plus 5-HT s.c. was comparable ipsilateral and contralateral to the injection site. The necrosis following CP plus 5-HT i.p. was maximal at 24 hr and remained fairly constant until 5 days. Regeneration was prominent by 7 days. The muscle necrosis  produced by CP plus 5-HT is blocked by some 5-HT blockers, e.g., methiotepin and methysergide. It is also partially blocked by denervation. The capacity of tricyclic antidepressants and antihistamines to block neuronal 5-HT reuptake tended to be negatively correlated with the capacity to potentiate the muscle necrosis they produced with 5-HT, which suggests that blockade of 5-HT uptake is not the mechanism of the pathology produced by the combined treatment. The tricyclic antidepressants and the antihistamines are \"membrane stabilizers-labilizers\". Other drugs which are \"membrane stabilizers-labilizers\" such as trihexyphenidyl and procaine also promoted skeletal muscle necrosis when given prior to 5-HT. It is proposed that the effects of imipramine plus 5-HT on skeletal muscle are not due to the blockade of neuronal uptake of 5-HT and subsequent vascular-induced ischemia, but reflect direct toxic effects of these agents on skeletal muscle.", "contents": "Skeletal muscle necrosis following membrane-active drugs plus serotonin. Administration of imipramine plus serotonin (5-HT) to rats has been proposed as an animal model of Duchenne muscular dystrophy. We studied the skeletal muscle necrosis produced in male rats given 5-HT after pretreatment with imipramine, other tricyclic antidepressants, or antihistamines, which like the tricyclic antidepressants, can block neuronal reuptake of 5-HT. Following one of these agents plus 5-HT, 20 mg/kg subcutaneously (s.c.), necrosis was more severe in the soleus muscle than the quadriceps. There was no significant difference in the incidence of necrosis in the soleus and quadriceps muscles following one of these agents plus 5-HT, 100 mg/kg, intraperitoneally (i.p.). After one of these agents plus 5-HT i.p., but not 5-HT s.c., extensive necrosis was significantly more frequent and severe in the quadriceps muscle than after 5-HT s.c. Chlorpheniramine (CP) plus 5-HT, 2.5 mg/kg intravenously, produced less muscle necrosis than CP plus 5-HT s.c. or i.p. The necrosis produced by CP plus 5-HT s.c. was comparable ipsilateral and contralateral to the injection site. The necrosis following CP plus 5-HT i.p. was maximal at 24 hr and remained fairly constant until 5 days. Regeneration was prominent by 7 days. The muscle necrosis  produced by CP plus 5-HT is blocked by some 5-HT blockers, e.g., methiotepin and methysergide. It is also partially blocked by denervation. The capacity of tricyclic antidepressants and antihistamines to block neuronal 5-HT reuptake tended to be negatively correlated with the capacity to potentiate the muscle necrosis they produced with 5-HT, which suggests that blockade of 5-HT uptake is not the mechanism of the pathology produced by the combined treatment. The tricyclic antidepressants and the antihistamines are \"membrane stabilizers-labilizers\". Other drugs which are \"membrane stabilizers-labilizers\" such as trihexyphenidyl and procaine also promoted skeletal muscle necrosis when given prior to 5-HT. It is proposed that the effects of imipramine plus 5-HT on skeletal muscle are not due to the blockade of neuronal uptake of 5-HT and subsequent vascular-induced ischemia, but reflect direct toxic effects of these agents on skeletal muscle."}
{"id": "PMID:6638", "title": "Time sequence of lipogenic changes in adipose tissue of rats when converted from ad libitum feeding to meal-eating.", "content": "This study was undertaken to establish the time sequence of lipogenic changes in adipose tissue of rats when converted from ad libitum feeding to meal-eating. Rats were fed a high carbohydrate diet 2 hours/day for 0 to 10 days (meal-eating). The high speed supernatant fraction from homogenized epididymal fat pads was assayed for citrate cleavage enzyme, acetyl CoA carboxylase, fatty acid synthetase and malic enzyme activities. The effects of meal-feeding on in vitro and in vivo rates of fatty acid synthesis in adipose tissue as well as the amounts of glycogen deposited in the adipose tissue were measured. During the first 10 days of meal-feeding, the lipogenic enzyme activities were actually decreased or unchanged in the meal-fed rats but during this time the in vitro and in vivo rates of fatty acid synthesis were progressively increased in the meal-fed rats. Glycogen levels in the adipose tissue of meal-fed rats were greater than the levels in the nibblers. The initial hyperlipogenesis observed in the meal-fed rat appears to be due to changes in substrate uptake by the adipose tissue and/or to alterations in enzyme activation in the adipose tissue rather than to changes in the quantity of enzyme present in the tissue.", "contents": "Time sequence of lipogenic changes in adipose tissue of rats when converted from ad libitum feeding to meal-eating. This study was undertaken to establish the time sequence of lipogenic changes in adipose tissue of rats when converted from ad libitum feeding to meal-eating. Rats were fed a high carbohydrate diet 2 hours/day for 0 to 10 days (meal-eating). The high speed supernatant fraction from homogenized epididymal fat pads was assayed for citrate cleavage enzyme, acetyl CoA carboxylase, fatty acid synthetase and malic enzyme activities. The effects of meal-feeding on in vitro and in vivo rates of fatty acid synthesis in adipose tissue as well as the amounts of glycogen deposited in the adipose tissue were measured. During the first 10 days of meal-feeding, the lipogenic enzyme activities were actually decreased or unchanged in the meal-fed rats but during this time the in vitro and in vivo rates of fatty acid synthesis were progressively increased in the meal-fed rats. Glycogen levels in the adipose tissue of meal-fed rats were greater than the levels in the nibblers. The initial hyperlipogenesis observed in the meal-fed rat appears to be due to changes in substrate uptake by the adipose tissue and/or to alterations in enzyme activation in the adipose tissue rather than to changes in the quantity of enzyme present in the tissue."}
{"id": "PMID:6639", "title": "Guanosine nucleotide precursor for flavinogenesis of Eremothecium Ashbyii.", "content": "The purine precursor in the riboflavin biosynthetic pathway in Eremothecium ashbyii was examined using a guanine analogue, 8-azaguanine, with non-growing cell systems. 1. Riboflavin formation in the culture filtrate was determined at 0, 5, 10 and 20 hr after start of the incubation of the non-growing cells in the presence of xanthine or 8-azaguanine (1 mM, respectively). At 20 hr of incubation, the addition of xanthine stimulated riboflavin formation by 36% and the addition of 8-azaguanine inhibited the formation by 57%. 2. Acid soluble nucleotide pools in the cells were followed at 0, 5, 10 and 20 hr of the incubation period in the presence of xanthine or 8-azaguanine by means of anion exchange column chromatography. The result showed that the GTP pool changed markedly despite the fact that the adenosine nucleotide pool was almost constant irrespective of the presence or absence of these purines till 10 hr of incubation. But, the decrease of the former was overcome in part by the addition of flavinogenic xanthine. Furthermore, the total amounts of GTP and guanosine accumulated in cells in the presence of 8-azaguanine reached the maximum already at 5 hr, attaining a level twice as much as the GTP contents of the control. 3. The role of guanosine nucleotide pool in riboflavin formation was further examined using 8-azaguanine. In this experiment the drug was added to the suspension of non-growing cells at 3 hr or 6 hr after the incubation was started and the reaction was continued till the 12th hr. A more clear-cut correlationship between riboflavin formation and guanosine nucleotide pool was oberved by this experiment. The guanosine nucleotide pool (consisting of GMP, GDP and GTP) increased simultaneously with the inhibition of riboflavin formation. Of the guanosine nucleotides pools, the GMP pool increased 2.7 times above normal upon the addition of 8-azaguanine during the incubation for 6 hr and 5.3 fold for 9 hr. While, the GTP pool increased 1.9 fold above normal for 6 hrs' incubation in the supplementation of this drug but decreased to one-half of the normal at the incubation period of 9 hr. In these cases, the decreased amounts of GTP were equal to the increased amounts of GMP during the incubation periods of 6 hr and 9 hr in the presence of added 8-azaguanine. 4. The above results suggest strongly that GTP is an immediate precursor of riboflavin in the form of nucleotide.", "contents": "Guanosine nucleotide precursor for flavinogenesis of Eremothecium Ashbyii. The purine precursor in the riboflavin biosynthetic pathway in Eremothecium ashbyii was examined using a guanine analogue, 8-azaguanine, with non-growing cell systems. 1. Riboflavin formation in the culture filtrate was determined at 0, 5, 10 and 20 hr after start of the incubation of the non-growing cells in the presence of xanthine or 8-azaguanine (1 mM, respectively). At 20 hr of incubation, the addition of xanthine stimulated riboflavin formation by 36% and the addition of 8-azaguanine inhibited the formation by 57%. 2. Acid soluble nucleotide pools in the cells were followed at 0, 5, 10 and 20 hr of the incubation period in the presence of xanthine or 8-azaguanine by means of anion exchange column chromatography. The result showed that the GTP pool changed markedly despite the fact that the adenosine nucleotide pool was almost constant irrespective of the presence or absence of these purines till 10 hr of incubation. But, the decrease of the former was overcome in part by the addition of flavinogenic xanthine. Furthermore, the total amounts of GTP and guanosine accumulated in cells in the presence of 8-azaguanine reached the maximum already at 5 hr, attaining a level twice as much as the GTP contents of the control. 3. The role of guanosine nucleotide pool in riboflavin formation was further examined using 8-azaguanine. In this experiment the drug was added to the suspension of non-growing cells at 3 hr or 6 hr after the incubation was started and the reaction was continued till the 12th hr. A more clear-cut correlationship between riboflavin formation and guanosine nucleotide pool was oberved by this experiment. The guanosine nucleotide pool (consisting of GMP, GDP and GTP) increased simultaneously with the inhibition of riboflavin formation. Of the guanosine nucleotides pools, the GMP pool increased 2.7 times above normal upon the addition of 8-azaguanine during the incubation for 6 hr and 5.3 fold for 9 hr. While, the GTP pool increased 1.9 fold above normal for 6 hrs' incubation in the supplementation of this drug but decreased to one-half of the normal at the incubation period of 9 hr. In these cases, the decreased amounts of GTP were equal to the increased amounts of GMP during the incubation periods of 6 hr and 9 hr in the presence of added 8-azaguanine. 4. The above results suggest strongly that GTP is an immediate precursor of riboflavin in the form of nucleotide."}
{"id": "PMID:6640", "title": "Lysozyme damage caused by secondary degradation products during the autoxidation process of linoleic acid.", "content": "Autoxidized LA is classified into four groups, LA, LAHPO, SP and FP. Lysozyme is inactivated by these products in the increasing order as follows: FP less than LA less than LAHPO less than SP. The effects of these products on the amino acid composition of lysozyme is examined. All kinds of amino acid residues were not damaged until lysozyme was incubated with LA and LAHPO at 45 degrees C for 100 days. The susceptible amino acid residues attacked by the autoxidized products are tryptophan, lysine and histidine. The specific loss of methionine by SP occurs during acid-hydrolysis. The effect of SP was the strongest among the autoxidized products. FP was almost noneffective. The destructive actions of BP, MA and PA were compared with those of autoxidized products. Effects of these compounds did not resemble those of autoxidized products. It was concluded that tryptophan, lysine and histidine residues were specifically attacked by SP.", "contents": "Lysozyme damage caused by secondary degradation products during the autoxidation process of linoleic acid. Autoxidized LA is classified into four groups, LA, LAHPO, SP and FP. Lysozyme is inactivated by these products in the increasing order as follows: FP less than LA less than LAHPO less than SP. The effects of these products on the amino acid composition of lysozyme is examined. All kinds of amino acid residues were not damaged until lysozyme was incubated with LA and LAHPO at 45 degrees C for 100 days. The susceptible amino acid residues attacked by the autoxidized products are tryptophan, lysine and histidine. The specific loss of methionine by SP occurs during acid-hydrolysis. The effect of SP was the strongest among the autoxidized products. FP was almost noneffective. The destructive actions of BP, MA and PA were compared with those of autoxidized products. Effects of these compounds did not resemble those of autoxidized products. It was concluded that tryptophan, lysine and histidine residues were specifically attacked by SP."}
{"id": "PMID:6642", "title": "Hypomagnesemia in infants of diabetic mothers: perinatal studies.", "content": "Fifty-six diabetic mothers and their infants were studied prospectively from birth. Twenty-one of 56 IDM had serum Mg less than or equal to 1.5 mg/dl, on at least one occasion during the first 3 days. Serum Mg in these hypomagnesemic infants did not demonstrate the normal increase with postnatal age that was present in normomagnesemic infants. Decreased neonatal serum Mg was related to increased severity of maternal diabetes, young mothers, mothers for lower gravidity, and prematurity. Decreased serum Mg, alone or with decreased ionized or total Ca, did not correlate with neuromuscular irritability in the infants. Decreased serum Mg in IDM was associated with decreased maternal serum Mg, decreased neonatal ionized and total Ca, increased serum P, and decreased parathyroid function. Serum Mg was not related to dietary P intake, or urinary Ca or P excretion. Thus, transitory neonatal hypomagnesemia occurs in IDM; it is speculated that factors causing HM might include maternal HM or neonatal hyperphosphatemia, and that the HM is related to the hypocalcemia and functional hypoparathyroidism of IDM.", "contents": "Hypomagnesemia in infants of diabetic mothers: perinatal studies. Fifty-six diabetic mothers and their infants were studied prospectively from birth. Twenty-one of 56 IDM had serum Mg less than or equal to 1.5 mg/dl, on at least one occasion during the first 3 days. Serum Mg in these hypomagnesemic infants did not demonstrate the normal increase with postnatal age that was present in normomagnesemic infants. Decreased neonatal serum Mg was related to increased severity of maternal diabetes, young mothers, mothers for lower gravidity, and prematurity. Decreased serum Mg, alone or with decreased ionized or total Ca, did not correlate with neuromuscular irritability in the infants. Decreased serum Mg in IDM was associated with decreased maternal serum Mg, decreased neonatal ionized and total Ca, increased serum P, and decreased parathyroid function. Serum Mg was not related to dietary P intake, or urinary Ca or P excretion. Thus, transitory neonatal hypomagnesemia occurs in IDM; it is speculated that factors causing HM might include maternal HM or neonatal hyperphosphatemia, and that the HM is related to the hypocalcemia and functional hypoparathyroidism of IDM."}
{"id": "PMID:6643", "title": "The stability of cannabis and its preparations on storage.", "content": "Solutions of pure cannabinoids, nine samples of herbal and two of resin cannabis (one freshly prepared) were stored in varying conditions for up to 2 years. Exposure to light (not direct sunlight) was shown to be the greatest single factos in loss of cannabinoids especially in solutions, which should therefore be protected from light during analytical and phytochemical operations. Previous claims that solutions in ethanol were stable have not been substantiated. The effect of temperature, up to 20 degrees, was insignificant but air oxidation did lead to significant losses. These could be reduced if care was taken to minimize damage to the glands which act as \"well filled, well closed containers\". Loss of tetrahydrocannabinol after exposure to light does not lead to an increase in cannabinol, but air oxidation in the dark does. It is concluded that carefully prepared herbal or resin cannabis or extracts are reasonably stable for 1 to 2 years if stored in the dark at room temperature.", "contents": "The stability of cannabis and its preparations on storage. Solutions of pure cannabinoids, nine samples of herbal and two of resin cannabis (one freshly prepared) were stored in varying conditions for up to 2 years. Exposure to light (not direct sunlight) was shown to be the greatest single factos in loss of cannabinoids especially in solutions, which should therefore be protected from light during analytical and phytochemical operations. Previous claims that solutions in ethanol were stable have not been substantiated. The effect of temperature, up to 20 degrees, was insignificant but air oxidation did lead to significant losses. These could be reduced if care was taken to minimize damage to the glands which act as \"well filled, well closed containers\". Loss of tetrahydrocannabinol after exposure to light does not lead to an increase in cannabinol, but air oxidation in the dark does. It is concluded that carefully prepared herbal or resin cannabis or extracts are reasonably stable for 1 to 2 years if stored in the dark at room temperature."}
{"id": "PMID:6644", "title": "Changes in the particle size distribution during tableting of sulphathiazole powder.", "content": "Five size fractions of sulphathiazole powder (volume surface mean diameter 155, 133, 86, 50 and 41 mum) were compressed into 12 mm diameter tablets on an instrumented single punch tablet machine. The size analysis of the tablet material after compression showed an attrition of the coarser fraction and an agglomeration of the finer fraction. It is postulated that there is a critical particle size where the effects of crushing and bonding cancel each other. The changes in particle size are discussed in relation to some of the compressive characteristics of the powder.", "contents": "Changes in the particle size distribution during tableting of sulphathiazole powder. Five size fractions of sulphathiazole powder (volume surface mean diameter 155, 133, 86, 50 and 41 mum) were compressed into 12 mm diameter tablets on an instrumented single punch tablet machine. The size analysis of the tablet material after compression showed an attrition of the coarser fraction and an agglomeration of the finer fraction. It is postulated that there is a critical particle size where the effects of crushing and bonding cancel each other. The changes in particle size are discussed in relation to some of the compressive characteristics of the powder."}
{"id": "PMID:6645", "title": "Release of a drug from homogeneous ointments containing the drug in solution.", "content": "The rate of release of resorcinol (5%) from hydrogels (Carbopol, sodium carboxymethylcellulose, starch), lipogels (alcoholic-base, esteric-bases containing different amounts of beeswax with and without a spreading additive, respectively) and Labrafils has been examined. For the experimental design adopted the release of the drug is linear between 10 and 70% of the amount of drug released. The results agree well with the mathematical model postulated by Higuchi (1962) for the release of a drug from homogeneous ointments containing the drug in solution.", "contents": "Release of a drug from homogeneous ointments containing the drug in solution. The rate of release of resorcinol (5%) from hydrogels (Carbopol, sodium carboxymethylcellulose, starch), lipogels (alcoholic-base, esteric-bases containing different amounts of beeswax with and without a spreading additive, respectively) and Labrafils has been examined. For the experimental design adopted the release of the drug is linear between 10 and 70% of the amount of drug released. The results agree well with the mathematical model postulated by Higuchi (1962) for the release of a drug from homogeneous ointments containing the drug in solution."}
{"id": "PMID:6646", "title": "The persistence of dextran 70 in blood plasma following its infusion, during surgery, for prophylaxis against thromboembolism.", "content": "An infusion of dextran (mean molecular weight 70000) in normal saline (either 1 litre or 500 ml) was given to patients undergoing hysterectomy. The infusion was started at induction of anaesthesia and continued throughout the operation and for up to 5 h thereafter. The rate of elimination of dextran was independent of the dose given. The time to eliminate half the dose was nearly two days and up to 10% was still present in the circulation after one week. The persistence of dextran in the plasma in these amounts and for this length of time may have considerable implications in the prophylaxis of postoperative deep venous thrombosis.", "contents": "The persistence of dextran 70 in blood plasma following its infusion, during surgery, for prophylaxis against thromboembolism. An infusion of dextran (mean molecular weight 70000) in normal saline (either 1 litre or 500 ml) was given to patients undergoing hysterectomy. The infusion was started at induction of anaesthesia and continued throughout the operation and for up to 5 h thereafter. The rate of elimination of dextran was independent of the dose given. The time to eliminate half the dose was nearly two days and up to 10% was still present in the circulation after one week. The persistence of dextran in the plasma in these amounts and for this length of time may have considerable implications in the prophylaxis of postoperative deep venous thrombosis."}
{"id": "PMID:6647", "title": "The absorption and elimination of metoclopramide in three animal species.", "content": "The absorption and elimination of metoclopramide have been studied in the rat, rabbit and dog. Thin-layer chromatography followed by photodensitometry was used for the analysis of the unchanged drug and its metabolites. N-De-ethylation is an important Phase I metabolic reaction and conjugation with glucoronic acid and sulphate is a major route of metabolism, particularly in the rabbit. The pharmacokinetic parameters after intravenous administration showed little interspecies variation. First order elimination kinetics with short half-lives and high apparent volumes of distribution (greater than 1.1 kg(-1)) were observed. Major interspecies variations were seen after oral administration of high doses of the drug. Metoclopramide was eliminated slowly after oral administration to rats. The findings in the rabbit and in the dog suggest that the liver plays an active role reducing the systemic availability of unchanged metoclopramide after oral administration.", "contents": "The absorption and elimination of metoclopramide in three animal species. The absorption and elimination of metoclopramide have been studied in the rat, rabbit and dog. Thin-layer chromatography followed by photodensitometry was used for the analysis of the unchanged drug and its metabolites. N-De-ethylation is an important Phase I metabolic reaction and conjugation with glucoronic acid and sulphate is a major route of metabolism, particularly in the rabbit. The pharmacokinetic parameters after intravenous administration showed little interspecies variation. First order elimination kinetics with short half-lives and high apparent volumes of distribution (greater than 1.1 kg(-1)) were observed. Major interspecies variations were seen after oral administration of high doses of the drug. Metoclopramide was eliminated slowly after oral administration to rats. The findings in the rabbit and in the dog suggest that the liver plays an active role reducing the systemic availability of unchanged metoclopramide after oral administration."}
{"id": "PMID:6648", "title": "Release of prostaglandin E-like material from perfused mesenteric blood vessels of rabbits.", "content": "Infusions of noradrenaline (1-3 mug ml(-1) min(-1)) into the mesenteric vascular preparation of the rabbit caused a 2 to 5 fold rise in perfusion pressure and a release of prostaglandin E-like material (3.23 +/- 0.65 (s.e.) ng PGE2 equivalents ml(-1)). Indomethacin (3 mug ml(-1)) prevented whereas arachidonic acid (0.2 mug ml(-1)) augmented, the noradrenaline-evoked release of a prostaglandin E-like material. The walls of arterioles or precapillary vessels are the proposed site of prostaglandin generation.", "contents": "Release of prostaglandin E-like material from perfused mesenteric blood vessels of rabbits. Infusions of noradrenaline (1-3 mug ml(-1) min(-1)) into the mesenteric vascular preparation of the rabbit caused a 2 to 5 fold rise in perfusion pressure and a release of prostaglandin E-like material (3.23 +/- 0.65 (s.e.) ng PGE2 equivalents ml(-1)). Indomethacin (3 mug ml(-1)) prevented whereas arachidonic acid (0.2 mug ml(-1)) augmented, the noradrenaline-evoked release of a prostaglandin E-like material. The walls of arterioles or precapillary vessels are the proposed site of prostaglandin generation."}
{"id": "PMID:6649", "title": "Kininogen and kininogenase synthesis by the liver of normal and injured rats.", "content": "Isolated livers from normal rats or from others at 2 days after subcutaneous injection of turpentine have been perfused with a simplified medium. Estimation of kininogen, kininogenase and 2 plasma proteins in the perfusates thus obtained indicate that both kininogen and kininogenase are synthesized in the liver. Furthermore, because twice as much kininogen and kininogenase was synthesized by the livers from the rats which had been injected with turpentine as by those from the normal rats, these two proteins must be considered to be members of the group of plasma proteins known as acute phase reactants.", "contents": "Kininogen and kininogenase synthesis by the liver of normal and injured rats. Isolated livers from normal rats or from others at 2 days after subcutaneous injection of turpentine have been perfused with a simplified medium. Estimation of kininogen, kininogenase and 2 plasma proteins in the perfusates thus obtained indicate that both kininogen and kininogenase are synthesized in the liver. Furthermore, because twice as much kininogen and kininogenase was synthesized by the livers from the rats which had been injected with turpentine as by those from the normal rats, these two proteins must be considered to be members of the group of plasma proteins known as acute phase reactants."}
{"id": "PMID:6650", "title": "The effect of some polyene macrolides on absorption from the small intestine in the rat.", "content": "The effect of three polyene macrolides, candicidin, amphotericin B and nystatin on the absorption of [3H] cholesterol was studied in the rat by using the in situ gut loop perfusion technique. Chronic treatment with candicidin and its presence at various concentrations in the gut loop perfusion experiments inhibited [3H] cholesterol absorption although a smaller effect was also obtained with amphotericin B and nystatin at higher concentrations. A similar but much less pronounced action of candicidin was also observed on the absorption of [3H] corticosterone and [14C] phenytoin.", "contents": "The effect of some polyene macrolides on absorption from the small intestine in the rat. The effect of three polyene macrolides, candicidin, amphotericin B and nystatin on the absorption of [3H] cholesterol was studied in the rat by using the in situ gut loop perfusion technique. Chronic treatment with candicidin and its presence at various concentrations in the gut loop perfusion experiments inhibited [3H] cholesterol absorption although a smaller effect was also obtained with amphotericin B and nystatin at higher concentrations. A similar but much less pronounced action of candicidin was also observed on the absorption of [3H] corticosterone and [14C] phenytoin."}
{"id": "PMID:6651", "title": "An assessment of the cardiovascular sympathectomy induced by guanethidine.", "content": "Guanethidine treatment of rate (30 mg kg(-1), i.p. daily for 6 weeks) produced a profound reduction in the catecholamine present (as indicated by fluorescence histochemistry and catecholamine determinations) in tissues taken from the cardiovascular system, but there was evidence of the return of catecholamines within 8 weeks. While these changes are consistent with a sympathectomy, the unaltered pressor responses to physostigmine (100 mug kg(-1), i.v.) and to carotid occlusion indicate an unimpaired functional capacity of noradrenergic nerves supplying the cardiovascular system. Although part of the response may be attributed to the unaffected adrenal medulla enhanced by the presence of considerable supersensitivity as shown to exogenous noradrenaline, there would appear to be a dissociation between the results obtained from physical and functional tests of the sympathectomy induced by guanethidine.", "contents": "An assessment of the cardiovascular sympathectomy induced by guanethidine. Guanethidine treatment of rate (30 mg kg(-1), i.p. daily for 6 weeks) produced a profound reduction in the catecholamine present (as indicated by fluorescence histochemistry and catecholamine determinations) in tissues taken from the cardiovascular system, but there was evidence of the return of catecholamines within 8 weeks. While these changes are consistent with a sympathectomy, the unaltered pressor responses to physostigmine (100 mug kg(-1), i.v.) and to carotid occlusion indicate an unimpaired functional capacity of noradrenergic nerves supplying the cardiovascular system. Although part of the response may be attributed to the unaffected adrenal medulla enhanced by the presence of considerable supersensitivity as shown to exogenous noradrenaline, there would appear to be a dissociation between the results obtained from physical and functional tests of the sympathectomy induced by guanethidine."}
{"id": "PMID:6662", "title": "Some formulation factors affecting the tensile strength, disintegration and dissolution of uncoated oxytetracycline tablets.", "content": "A study has been made of the effects of gelatin binding agent and moisture content on the tensile strength, disintegration and dissolution times of oxytetracycline tablets. These properties all increase with the gelatin content, and maximum tensile strengths occur when the tablets contain between 2.5 and 4.5% w/w of moisture. The properties of the tablets depend on their packing fraction and in general, the disintegration and dissolution times are minimal when the packing fraction is between 0.77 and 0.82. A connection has been established between the disintegration times of the tablets and the time required for 50% of the drug content to dissolve.", "contents": "Some formulation factors affecting the tensile strength, disintegration and dissolution of uncoated oxytetracycline tablets. A study has been made of the effects of gelatin binding agent and moisture content on the tensile strength, disintegration and dissolution times of oxytetracycline tablets. These properties all increase with the gelatin content, and maximum tensile strengths occur when the tablets contain between 2.5 and 4.5% w/w of moisture. The properties of the tablets depend on their packing fraction and in general, the disintegration and dissolution times are minimal when the packing fraction is between 0.77 and 0.82. A connection has been established between the disintegration times of the tablets and the time required for 50% of the drug content to dissolve."}
{"id": "PMID:6667", "title": "Factors affecting the binding of tricyclic tranquillizers and antidepressants to human serum albumin.", "content": "The linear free energy-related model for structure activity relations developed by Hansch & Fujita (1964) has been used to correlate the binding of tricylic tranquillizers and antidepressants to human serum albumin (HSA) with hydrophobic and electronic parameters. The parameters chosen being the chromatographic parameter (Rm) and the affinity of charge transfer complex formation (kc). The relative importance of these factors has been assessed by linear and multiple linear regression analysis. Results show that the major factor in binding is electronic with only a minor contribution from the hydrophobic parameter.", "contents": "Factors affecting the binding of tricyclic tranquillizers and antidepressants to human serum albumin. The linear free energy-related model for structure activity relations developed by Hansch & Fujita (1964) has been used to correlate the binding of tricylic tranquillizers and antidepressants to human serum albumin (HSA) with hydrophobic and electronic parameters. The parameters chosen being the chromatographic parameter (Rm) and the affinity of charge transfer complex formation (kc). The relative importance of these factors has been assessed by linear and multiple linear regression analysis. Results show that the major factor in binding is electronic with only a minor contribution from the hydrophobic parameter."}
{"id": "PMID:6668", "title": "Reversed ester analogues of pethidine: isomeric 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidines.", "content": "The preparation and stereochemical characterization of all three isomeric forms of 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidine is described. Of these, only the t-2-Me, c-6-Me, r-4-OCOMe isomer was an effective analgesic in mice (2.3 X pethidine) as judged by the hot-plate test. The results, together with reported data, demonstrate the potency raising effects of axial methyl alpha- to nitrogen and the lowering action of equatorial alpha-methyl substituents in reversed esters of pethidine.", "contents": "Reversed ester analogues of pethidine: isomeric 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidines. The preparation and stereochemical characterization of all three isomeric forms of 4-acetoxy-1, 2, 6-trimethyl-4-phenylpiperidine is described. Of these, only the t-2-Me, c-6-Me, r-4-OCOMe isomer was an effective analgesic in mice (2.3 X pethidine) as judged by the hot-plate test. The results, together with reported data, demonstrate the potency raising effects of axial methyl alpha- to nitrogen and the lowering action of equatorial alpha-methyl substituents in reversed esters of pethidine."}
{"id": "PMID:6669", "title": "Studies with the International Pyrogen Standard on the sensitivity and reproducibility of pharmacopoeial pyrogen testing.", "content": "Rabbits, 27 or 36 in each experiment, were injected with the International Pyrogen Standard (I.P.St.) in different seasons. The maximum temperature rises were registered, randomized and interpreted according to the requirements of the B.P. (1973), U.S.P. (1970), P. Hung. (1970) and P. Nord. (1962). Although the dose of 3.5 ng kg(-1) I.P.St. proved to be non-pyrogenic as tested in summer, when tested in winter the same dose was qualified pyrogenic (to be rejected) by up to one third of the combinations by the criteria of the four Pharmacopoeias. In the spring experiment \"to be rejected\" qualifications predominated as based on the response of large groups of rabbits. Exclusion of the rabbits showing low sensitivity (before randomization) barely influenced the results with 3.5 ng kg(-1) I.P.St. in the experiment in which the mean temperature rise was 0.49 degrees. If, however, the mean temperature rise was higher (0.57 or 0.69 degrees), such a selection practically resulted in the disappearance of \"passable\" qualifications in the triplet groups and a great predominance of \"to be rejected\" qualifications in the larger groups. The dose 7.0 ng kg(-1) consistently proved to be pyrogenic in large groups of rabbits.", "contents": "Studies with the International Pyrogen Standard on the sensitivity and reproducibility of pharmacopoeial pyrogen testing. Rabbits, 27 or 36 in each experiment, were injected with the International Pyrogen Standard (I.P.St.) in different seasons. The maximum temperature rises were registered, randomized and interpreted according to the requirements of the B.P. (1973), U.S.P. (1970), P. Hung. (1970) and P. Nord. (1962). Although the dose of 3.5 ng kg(-1) I.P.St. proved to be non-pyrogenic as tested in summer, when tested in winter the same dose was qualified pyrogenic (to be rejected) by up to one third of the combinations by the criteria of the four Pharmacopoeias. In the spring experiment \"to be rejected\" qualifications predominated as based on the response of large groups of rabbits. Exclusion of the rabbits showing low sensitivity (before randomization) barely influenced the results with 3.5 ng kg(-1) I.P.St. in the experiment in which the mean temperature rise was 0.49 degrees. If, however, the mean temperature rise was higher (0.57 or 0.69 degrees), such a selection practically resulted in the disappearance of \"passable\" qualifications in the triplet groups and a great predominance of \"to be rejected\" qualifications in the larger groups. The dose 7.0 ng kg(-1) consistently proved to be pyrogenic in large groups of rabbits."}
{"id": "PMID:6670", "title": "Gastrointestinal absorption of carbenoxolone in the rat determined in vitro and in situ: deviations from the pH-partition hypothesis.", "content": "The absorption of [14C] carbenoxolone from everted rat ileum in vitro and from rat stomach and ileum in situ has been examined. The rate of its mucosal to serosal transfer in vitro increases as pH increases from 5 to 8 whereas the amount bound to ileum tissue decreases with increased pH; absorption closely parallels the drug's solubility. The uptake of carbenoxolone in situ is bi-exponential and the rate constants for the two processes, have been calculated. Absorption in situ, and biliary excretion, of the drug increases with increasing pH from 5.0 to 7.4. Tissue binding to the ileum in situ is not dependent on pH except below pH 5.0 when extensive tissue accumulation of carbenoxolone occurs because of its low solubility. Tissue binding to the stomach increases markedly with decrease of pH from 7.4 to 6.5 and at pH 6.5 is 80 times greater than binding to the intestine. The rate of absorption from the stomach, at pH 6.5-7.4, was much less than that from the intestine in situ. When allowance is made for the binding of carbenoxolone to the stomach, contrary to the pH-partition hypothesis, correlation is apparent between its absorption and the amount present in the ionized form.", "contents": "Gastrointestinal absorption of carbenoxolone in the rat determined in vitro and in situ: deviations from the pH-partition hypothesis. The absorption of [14C] carbenoxolone from everted rat ileum in vitro and from rat stomach and ileum in situ has been examined. The rate of its mucosal to serosal transfer in vitro increases as pH increases from 5 to 8 whereas the amount bound to ileum tissue decreases with increased pH; absorption closely parallels the drug's solubility. The uptake of carbenoxolone in situ is bi-exponential and the rate constants for the two processes, have been calculated. Absorption in situ, and biliary excretion, of the drug increases with increasing pH from 5.0 to 7.4. Tissue binding to the ileum in situ is not dependent on pH except below pH 5.0 when extensive tissue accumulation of carbenoxolone occurs because of its low solubility. Tissue binding to the stomach increases markedly with decrease of pH from 7.4 to 6.5 and at pH 6.5 is 80 times greater than binding to the intestine. The rate of absorption from the stomach, at pH 6.5-7.4, was much less than that from the intestine in situ. When allowance is made for the binding of carbenoxolone to the stomach, contrary to the pH-partition hypothesis, correlation is apparent between its absorption and the amount present in the ionized form."}
{"id": "PMID:6671", "title": "Effects of phosvitin on the ecg changes induced under hypoxia in the rat.", "content": "The effect of phosvitin (1 g kg(-1), i.p.) on ecg changes induced in rats by a reduction of partial oxygen pressure in the respiratory mixture was studied. Phosphocreatine, phosphoserine, ATP and Na2HPO42H2O were also administered intraperitoneally for comparison. Phosvitin alone was found to prevent the hypoxia-induced T-wave changes (flattening or disappearance), which were also temporarily aggravated by injection of noradrenaline. As to the metabolic, hypoxia-induced myocardial changes, two hypotheses are discussed: a release of phosvitin phosphate radicals ready for immediate utilization or a drug action mediated via a membrane-bound intrinsic proteinkinase system.", "contents": "Effects of phosvitin on the ecg changes induced under hypoxia in the rat. The effect of phosvitin (1 g kg(-1), i.p.) on ecg changes induced in rats by a reduction of partial oxygen pressure in the respiratory mixture was studied. Phosphocreatine, phosphoserine, ATP and Na2HPO42H2O were also administered intraperitoneally for comparison. Phosvitin alone was found to prevent the hypoxia-induced T-wave changes (flattening or disappearance), which were also temporarily aggravated by injection of noradrenaline. As to the metabolic, hypoxia-induced myocardial changes, two hypotheses are discussed: a release of phosvitin phosphate radicals ready for immediate utilization or a drug action mediated via a membrane-bound intrinsic proteinkinase system."}
{"id": "PMID:6672", "title": "The transport of tetracyclines across the mouse ileum in vitro: the effect of cations and other agents.", "content": "The intestinal transfer of different tetracyclines dissolved in calcium- and magnesium-free Krebs bicarbonate buffer solution, pH 7.4, was studied using the everted ileum of the mouse. The rates of transfer of chlortetracycline and demethylchlortetracycline were less than those of tetracycline and oxytetracycline, the latter compounds being transferred at the same rate. Addition of calcium and magnesium to the buffer greatly reduced the transfer of tetracycline; this inhibition could be antagonized by EDTA. The presence of iron also inhibited the transfer of tetracycline. The inhibitory effect of these ions on tetracycline transfer seemed due to chelation of the drug. Glucosamine and acetylmethionine, but not acetyl glucosamine, diminished the intestinal transfer of tetracyclines. The former two agents did not influence the uptake of tissue fluids. Tetracycline was also transfered from the serous to the mucous coat in the non-everted intestinal sac of mice. The above observations suggested that the absorption of tetracyclines was not due solely to passive diffusion.", "contents": "The transport of tetracyclines across the mouse ileum in vitro: the effect of cations and other agents. The intestinal transfer of different tetracyclines dissolved in calcium- and magnesium-free Krebs bicarbonate buffer solution, pH 7.4, was studied using the everted ileum of the mouse. The rates of transfer of chlortetracycline and demethylchlortetracycline were less than those of tetracycline and oxytetracycline, the latter compounds being transferred at the same rate. Addition of calcium and magnesium to the buffer greatly reduced the transfer of tetracycline; this inhibition could be antagonized by EDTA. The presence of iron also inhibited the transfer of tetracycline. The inhibitory effect of these ions on tetracycline transfer seemed due to chelation of the drug. Glucosamine and acetylmethionine, but not acetyl glucosamine, diminished the intestinal transfer of tetracyclines. The former two agents did not influence the uptake of tissue fluids. Tetracycline was also transfered from the serous to the mucous coat in the non-everted intestinal sac of mice. The above observations suggested that the absorption of tetracyclines was not due solely to passive diffusion."}
{"id": "PMID:6673", "title": "Some pharmacological properties of the venom, venom fractions and pure toxin of the yellow-bellied sea snake Pelamis platurus.", "content": "The effects of the crude venom, four partially purified venom fractions and pure toxin (Pelamis toxin alpha) from yellow-bellied sea snake, Pelamis platurus, on respiration, blood pressure, heart and skeletal muscle of rabbits have been examined. Results indicated that crude venom, a partially purified toxic fraction and Pelamis toxin alpha caused initial respiratory stimulant effects followed by respiratory paralysis. In most cases, respiratory paralysis occurred before a profound fall in arterial pressure. Depression of the twitch response to nerve stimulation was observed in the tibialis anterior muscle. No significant change in the electrocardiogram was seen. Three partially purified non-toxic fractions of the crude venom induced transient respiratory stimulant effects. It was concluded that the crude venom and Pelamis toxin alpha had an identical mode of action and that they caused respiratory paralysis in rabbits.", "contents": "Some pharmacological properties of the venom, venom fractions and pure toxin of the yellow-bellied sea snake Pelamis platurus. The effects of the crude venom, four partially purified venom fractions and pure toxin (Pelamis toxin alpha) from yellow-bellied sea snake, Pelamis platurus, on respiration, blood pressure, heart and skeletal muscle of rabbits have been examined. Results indicated that crude venom, a partially purified toxic fraction and Pelamis toxin alpha caused initial respiratory stimulant effects followed by respiratory paralysis. In most cases, respiratory paralysis occurred before a profound fall in arterial pressure. Depression of the twitch response to nerve stimulation was observed in the tibialis anterior muscle. No significant change in the electrocardiogram was seen. Three partially purified non-toxic fractions of the crude venom induced transient respiratory stimulant effects. It was concluded that the crude venom and Pelamis toxin alpha had an identical mode of action and that they caused respiratory paralysis in rabbits."}
{"id": "PMID:6687", "title": "The influence of crystal form on the radial stress transmission characteristics of pharmaceutical materials.", "content": "Various crystal forms of sulphathiazole, barbitone and aspirin were compressed in a single-punch tablet machine instrumented to monitor axially applied and radially transmitted forces, and upper punch movement. The changes in radial stress during the compression cycle depended upon the polymorphic form of the compressed material. The results were rationalized in terms of the degree of plastic flow/crushing that occurred with each material, and the degree to which the final compact underwent elastic compression. It is postulated that the reduction in the transition temperature of polymorphic forms of sulphathiazole and barbitone and the polymorphic transition of sulphathiazole Form II was due to the production of dislocations in the crystal and the crystals at crystal boundaries formed in the compressed materials.", "contents": "The influence of crystal form on the radial stress transmission characteristics of pharmaceutical materials. Various crystal forms of sulphathiazole, barbitone and aspirin were compressed in a single-punch tablet machine instrumented to monitor axially applied and radially transmitted forces, and upper punch movement. The changes in radial stress during the compression cycle depended upon the polymorphic form of the compressed material. The results were rationalized in terms of the degree of plastic flow/crushing that occurred with each material, and the degree to which the final compact underwent elastic compression. It is postulated that the reduction in the transition temperature of polymorphic forms of sulphathiazole and barbitone and the polymorphic transition of sulphathiazole Form II was due to the production of dislocations in the crystal and the crystals at crystal boundaries formed in the compressed materials."}
{"id": "PMID:6688", "title": "Use of the mouse jumping test for estimating antagonistic potencies of morphine antagonists.", "content": "The potencies of 19 reference morphine antagonists have been compared in a modified version of the mouse jumping test. Mice were each implanted subcutaneously with one 75 mg pellet of morphine. Antagonist challenge took place 72 h later and the incidence of repetitive vertical-jumping was monitored over 1 h. A high Pearson correlation coefficient (r = 0.997) was found between quantitative assays based on the total number of jumps per mouse and quantal assays based on mice jumping at least 6 times. A comparison of relative potencies obtained with the mouse test and with non-withdrawn morphine-dependent monkeys gave a Spearman rank order coefficient of 0.91 while a similar comparison with values obtained with the guinea-pig isolated ileum preparation also gave a high correlation coefficient (r= 0.92). Whereas it is difficult to assess the antagonistic component of buprenorphine and cyclorphan with the ileum preparation, both compounds can be satisfactorily assayed in the mouse jumping test. The reported antagonistic properties of ketocyclazocine and profadol could not be confirmed in the mouse model.", "contents": "Use of the mouse jumping test for estimating antagonistic potencies of morphine antagonists. The potencies of 19 reference morphine antagonists have been compared in a modified version of the mouse jumping test. Mice were each implanted subcutaneously with one 75 mg pellet of morphine. Antagonist challenge took place 72 h later and the incidence of repetitive vertical-jumping was monitored over 1 h. A high Pearson correlation coefficient (r = 0.997) was found between quantitative assays based on the total number of jumps per mouse and quantal assays based on mice jumping at least 6 times. A comparison of relative potencies obtained with the mouse test and with non-withdrawn morphine-dependent monkeys gave a Spearman rank order coefficient of 0.91 while a similar comparison with values obtained with the guinea-pig isolated ileum preparation also gave a high correlation coefficient (r= 0.92). Whereas it is difficult to assess the antagonistic component of buprenorphine and cyclorphan with the ileum preparation, both compounds can be satisfactorily assayed in the mouse jumping test. The reported antagonistic properties of ketocyclazocine and profadol could not be confirmed in the mouse model."}
{"id": "PMID:6689", "title": "The narcotic discriminative stimulus complex: relation to analgesic activity.", "content": "The ability of drugs to produce the narcotic discriminative stimulus complex is found to be highly correlated with their analgesic activity; in contrast, no relation with their antidiarrhoeal activity is evident. The findings suggest that the narcotic discriminative stimulus complex is a centrally mediated effect of narcotic drugs.", "contents": "The narcotic discriminative stimulus complex: relation to analgesic activity. The ability of drugs to produce the narcotic discriminative stimulus complex is found to be highly correlated with their analgesic activity; in contrast, no relation with their antidiarrhoeal activity is evident. The findings suggest that the narcotic discriminative stimulus complex is a centrally mediated effect of narcotic drugs."}
{"id": "PMID:6690", "title": "A sensitive biological assay for prostaglandin E and acetylcholine.", "content": "Superfused hamster stomach strip has been used in the bioassay of prostaglandin E2 (PGE2) and acetylcholine. The preparation proved very stable and had no spontaneous movements. The sensitivity to PGE2 (and PGE1) was in the range of 10(-9) g ml(-1) and to acetylcholine 10(-12) g ml(-1). After treatment with physostigmine the sensitivity to acetylcholine was 10(-15) g ml(-1). In acetylcholine determination the preparation is more sensitive than any other method.", "contents": "A sensitive biological assay for prostaglandin E and acetylcholine. Superfused hamster stomach strip has been used in the bioassay of prostaglandin E2 (PGE2) and acetylcholine. The preparation proved very stable and had no spontaneous movements. The sensitivity to PGE2 (and PGE1) was in the range of 10(-9) g ml(-1) and to acetylcholine 10(-12) g ml(-1). After treatment with physostigmine the sensitivity to acetylcholine was 10(-15) g ml(-1). In acetylcholine determination the preparation is more sensitive than any other method."}
{"id": "PMID:6691", "title": "Intestinal pH and propulsion: an explanation of diarrhoea in lactase deficiency and laxation by lactulose.", "content": "Subjects deficient in lactase may experience bloating, cramps and diarrhoea after ingesting milk, due to the unhydrolysed and poorly-absorbed lactose. The diarrhoea may result from an osmotic effect of the lactose itself or its poorly-absorbed acidic products of fermentation (Weijers, van de Kamer & others, 1961; Christopher & Bayless, 1971), possibly together with an alteration of sodium and water absorption due to the lowered colonic pH (Rousseau & Sladen, 1971). Laxation by lactulose (1-4-beta-galactosidofructose) may operate through an analogous mechanism. The drug is a synthetic dissaccharide which, in oral doses of 10-20 g, relieves chronic constipation (Wesselius-de Casparis, Braadbaart & others, 1968). It is neither hydrolysed by intestinal dissaccharidase (Dahlqvist & Gryboski, 1965) nor absorbed in the gut, but it is converted in the colon mainly to lactic and acetic acids by various bacteria including Lactobacillus acidophilus. Apart from the increased osmotic effect, the pH in the proximal colon falls markedly (Bown, Gibson & others, 1974), and larger doses may reduce stool pH. Weijers & others (1961) inferred that the acidic products formed from lactose in the colon stimulate propulsion, and K.S. Liem (Philips-Duphar) suggested to us that lactulose may relieve constipation partly by stimulation of propulsion due to the lowered pH. The experiments described below support this view.", "contents": "Intestinal pH and propulsion: an explanation of diarrhoea in lactase deficiency and laxation by lactulose. Subjects deficient in lactase may experience bloating, cramps and diarrhoea after ingesting milk, due to the unhydrolysed and poorly-absorbed lactose. The diarrhoea may result from an osmotic effect of the lactose itself or its poorly-absorbed acidic products of fermentation (Weijers, van de Kamer & others, 1961; Christopher & Bayless, 1971), possibly together with an alteration of sodium and water absorption due to the lowered colonic pH (Rousseau & Sladen, 1971). Laxation by lactulose (1-4-beta-galactosidofructose) may operate through an analogous mechanism. The drug is a synthetic dissaccharide which, in oral doses of 10-20 g, relieves chronic constipation (Wesselius-de Casparis, Braadbaart & others, 1968). It is neither hydrolysed by intestinal dissaccharidase (Dahlqvist & Gryboski, 1965) nor absorbed in the gut, but it is converted in the colon mainly to lactic and acetic acids by various bacteria including Lactobacillus acidophilus. Apart from the increased osmotic effect, the pH in the proximal colon falls markedly (Bown, Gibson & others, 1974), and larger doses may reduce stool pH. Weijers & others (1961) inferred that the acidic products formed from lactose in the colon stimulate propulsion, and K.S. Liem (Philips-Duphar) suggested to us that lactulose may relieve constipation partly by stimulation of propulsion due to the lowered pH. The experiments described below support this view."}
{"id": "PMID:6692", "title": "Acetylcholinesterase and responses to acetylcholine in the embryonic chicken heart.", "content": "Three and 4 day old embryonic chicken hearts were examined for their responsiveness to acetylcholine and presence of acetylcholinesterase (AChE) to determine the role of the enzyme in the cardiac effects of the transmitter. The effects of acetylcholine on rate and contractility of 3 day old hearts were indistinguishable from those on 4 day old hearts. The effects were readily blocked by atropine at both stages of development. In 3 day old hearts the responses to acetylcholine were not affected by the AChE inhibitor physostigmine but in 4 day old hearts they were considerably potentiated. The effect of acetylcholine on the rates of 4 day old hearts is of short duration (5 min or less). In 3 day old hearts it persists for a much longer time. Thus, the appearance of AChE in the embryonic heart of the chicken does not seem to modify the responsiveness of the cholinergic receptor to the transmitter.", "contents": "Acetylcholinesterase and responses to acetylcholine in the embryonic chicken heart. Three and 4 day old embryonic chicken hearts were examined for their responsiveness to acetylcholine and presence of acetylcholinesterase (AChE) to determine the role of the enzyme in the cardiac effects of the transmitter. The effects of acetylcholine on rate and contractility of 3 day old hearts were indistinguishable from those on 4 day old hearts. The effects were readily blocked by atropine at both stages of development. In 3 day old hearts the responses to acetylcholine were not affected by the AChE inhibitor physostigmine but in 4 day old hearts they were considerably potentiated. The effect of acetylcholine on the rates of 4 day old hearts is of short duration (5 min or less). In 3 day old hearts it persists for a much longer time. Thus, the appearance of AChE in the embryonic heart of the chicken does not seem to modify the responsiveness of the cholinergic receptor to the transmitter."}
{"id": "PMID:6693", "title": "The effect of propranolol on sympathetic nerve stimulation in isolated vasa deferentia.", "content": "(+/-)-Propranolol hydrochloride (0.5 mg kg(-1) twice daily, subcutaneously, for 3 days or approximately 2.4 mg kg(-1) daily, orally, for 21 days) failed to produce ptosis or to affect responses to transmural stimulation of isolated vasa deferentia removed from treated mice. In guinea-pig isolated vasa deferentia responses to transmural stimulation through parallel electrodes were reduced by propranolol (1 to 20 mug ml(-1); blockade was concentration dependent, fast to equilibrium (45 min), easily reversed by washing but not reversed by (+)-amphetamine sulphate (0.2 mug ml(-1). At lower concentrations (0.04 and 0.2 mug ml(-1), propranolol marginally potentiated responses to transmural stimulation. In contrast, guanethidine (0.2 mug ml(-1)) produced a slow onset blockade which was completely reversed by (+)-amphetamine. The response to electrical stimulation through concentric ring electrodes was reduced by low concentrations of propranolol but this effect is ascribed to the known local anaesthetic actions of propranolol and no evidence of true adrenergic neuron blockade was found.", "contents": "The effect of propranolol on sympathetic nerve stimulation in isolated vasa deferentia. (+/-)-Propranolol hydrochloride (0.5 mg kg(-1) twice daily, subcutaneously, for 3 days or approximately 2.4 mg kg(-1) daily, orally, for 21 days) failed to produce ptosis or to affect responses to transmural stimulation of isolated vasa deferentia removed from treated mice. In guinea-pig isolated vasa deferentia responses to transmural stimulation through parallel electrodes were reduced by propranolol (1 to 20 mug ml(-1); blockade was concentration dependent, fast to equilibrium (45 min), easily reversed by washing but not reversed by (+)-amphetamine sulphate (0.2 mug ml(-1). At lower concentrations (0.04 and 0.2 mug ml(-1), propranolol marginally potentiated responses to transmural stimulation. In contrast, guanethidine (0.2 mug ml(-1)) produced a slow onset blockade which was completely reversed by (+)-amphetamine. The response to electrical stimulation through concentric ring electrodes was reduced by low concentrations of propranolol but this effect is ascribed to the known local anaesthetic actions of propranolol and no evidence of true adrenergic neuron blockade was found."}
{"id": "PMID:6694", "title": "Some effects of urea on drug dissolution.", "content": "Solubilities and dissolution rates of salicylic acid have been determined in urea solutions at different pH values. Solubilities increased with pH and urea concentration; a solubilization mechanism was considered to be operating. The solubilization effect of urea was greatest on the non-ionzed moieties of the solute. Dissolution rates of salicylic acid increased with pH and urea concentration. The increase in dissolution rate paralleled increases in solubility. The role of solubilizing effect in the enhancement of dissolution rate by urea is discussed.", "contents": "Some effects of urea on drug dissolution. Solubilities and dissolution rates of salicylic acid have been determined in urea solutions at different pH values. Solubilities increased with pH and urea concentration; a solubilization mechanism was considered to be operating. The solubilization effect of urea was greatest on the non-ionzed moieties of the solute. Dissolution rates of salicylic acid increased with pH and urea concentration. The increase in dissolution rate paralleled increases in solubility. The role of solubilizing effect in the enhancement of dissolution rate by urea is discussed."}
{"id": "PMID:6695", "title": "Solubilization of hydrocortisone, dexamethasone, testosterone and progesterone by long-chain polyoxyethylene surfactants.", "content": "Solubility and dialysis methods were used to study the solubilization of hydrocortisone, dexamethasone, testosterone and progesterone in aqueous long-chain polyoxyethylene non-ionic surfactant solutions. Partition coefficients, Km, between micellar and aqueous phases were calculated between 10-50 degrees. Km decreased with temperature and polyoxyethylene chain length but increased with decrease in steroid polarity. The standard free energy change, deltaGOS, for the solubilization of the steroids decreased with decrease in steroid polarity and surfactant hydrophilic chain length but was essentially independent of temperature. The enthalpies and entropies for the process were determined from the variation of Km with temperature. deltaHOS and deltaSOS increased with decreasing steroid polarity but were essentially independent of temperature and polyoxyethylene chain length.", "contents": "Solubilization of hydrocortisone, dexamethasone, testosterone and progesterone by long-chain polyoxyethylene surfactants. Solubility and dialysis methods were used to study the solubilization of hydrocortisone, dexamethasone, testosterone and progesterone in aqueous long-chain polyoxyethylene non-ionic surfactant solutions. Partition coefficients, Km, between micellar and aqueous phases were calculated between 10-50 degrees. Km decreased with temperature and polyoxyethylene chain length but increased with decrease in steroid polarity. The standard free energy change, deltaGOS, for the solubilization of the steroids decreased with decrease in steroid polarity and surfactant hydrophilic chain length but was essentially independent of temperature. The enthalpies and entropies for the process were determined from the variation of Km with temperature. deltaHOS and deltaSOS increased with decreasing steroid polarity but were essentially independent of temperature and polyoxyethylene chain length."}
{"id": "PMID:6696", "title": "Influence of non-ionic surfactants on permeation of hydrocortisone, dexamethasone, testosterone and progesterone across cellulose acetate membrane.", "content": "The lag-time method of diffusion has been used to investigate permeation of hydrocortisone, dexamethasone, testosterone and progesterone across cellulose acetate membranes between 10 degrees and 40 degrees. The process depended mainly on membrane-water partition coefficients of the steroids so that the least polar compound permeated the fastest. Permeation generally increased with increasing temperature and from the temperature dependance of the diffusion coefficient, energies of activation were derived. The varied from 2.4 kcal mol(-1) for the least polar steroid, progesterone, to 7.4 kcal mol(-1) for the most polar, hydrocortisone. n-C16 Polyoxyethylene surfactants when present below and above the cmc increased the steroids permeation rates. Varying the polyoxyethylene chain length (OE equals 17-63) did not significantly affect permeation rates, suggesting that the enhancing effect of surfactants arises from their hydrophobic group.", "contents": "Influence of non-ionic surfactants on permeation of hydrocortisone, dexamethasone, testosterone and progesterone across cellulose acetate membrane. The lag-time method of diffusion has been used to investigate permeation of hydrocortisone, dexamethasone, testosterone and progesterone across cellulose acetate membranes between 10 degrees and 40 degrees. The process depended mainly on membrane-water partition coefficients of the steroids so that the least polar compound permeated the fastest. Permeation generally increased with increasing temperature and from the temperature dependance of the diffusion coefficient, energies of activation were derived. The varied from 2.4 kcal mol(-1) for the least polar steroid, progesterone, to 7.4 kcal mol(-1) for the most polar, hydrocortisone. n-C16 Polyoxyethylene surfactants when present below and above the cmc increased the steroids permeation rates. Varying the polyoxyethylene chain length (OE equals 17-63) did not significantly affect permeation rates, suggesting that the enhancing effect of surfactants arises from their hydrophobic group."}
{"id": "PMID:6697", "title": "Oxytetracyline tablet formulations: effect of variations in binder concentration and volume on granule and tablet properties.", "content": "Formulation studies have been conducted on an oxytetracycline dihydrate tablet formulation containing microcrystalline cellulose and alginic acid, wet granulated with polyvinylpyrrolidone (PVP) solution. A range of granule properties including size, strength packing and porosity, and tablet properties including breaking load, porosity, disintegration and dissolution have been measured. Increased compaction pressure decreased tablet porosity. The reproducibility of the above properties was determined by tests on nine standard batches of granules and tablets. An increased concentration of PVP in the binder solution decreased the rate of tablet dissolution. Although the volume of granulating solution apparently controlled the granule size, it did not significantly alter the tablet dissolution, when the amount of PVP was constant.", "contents": "Oxytetracyline tablet formulations: effect of variations in binder concentration and volume on granule and tablet properties. Formulation studies have been conducted on an oxytetracycline dihydrate tablet formulation containing microcrystalline cellulose and alginic acid, wet granulated with polyvinylpyrrolidone (PVP) solution. A range of granule properties including size, strength packing and porosity, and tablet properties including breaking load, porosity, disintegration and dissolution have been measured. Increased compaction pressure decreased tablet porosity. The reproducibility of the above properties was determined by tests on nine standard batches of granules and tablets. An increased concentration of PVP in the binder solution decreased the rate of tablet dissolution. Although the volume of granulating solution apparently controlled the granule size, it did not significantly alter the tablet dissolution, when the amount of PVP was constant."}
{"id": "PMID:6698", "title": "Oxytetracycline tablet formulations: the influence of excipients and the method of granulation.", "content": "The proportion of microcrystalline cellulose and alginic acid present as excipients in the dry mix for an oxytetracycline dihydrate tablet formulation, prepared by a conventional wet granulation process, has been shown to influence granule formation and properties. Granule size distributions have varied widely due perhaps to variation in binder distribution. Granulating with water was equally satisfactory to granulating with a PVP solution. Slugged granules produced robust tablets, which disintegrated and dissolved rapidly.", "contents": "Oxytetracycline tablet formulations: the influence of excipients and the method of granulation. The proportion of microcrystalline cellulose and alginic acid present as excipients in the dry mix for an oxytetracycline dihydrate tablet formulation, prepared by a conventional wet granulation process, has been shown to influence granule formation and properties. Granule size distributions have varied widely due perhaps to variation in binder distribution. Granulating with water was equally satisfactory to granulating with a PVP solution. Slugged granules produced robust tablets, which disintegrated and dissolved rapidly."}
{"id": "PMID:6699", "title": "Oxytetracycline tablet formulations: the effect of wet mixing time, particle size and batch variation on granule and tablet properties.", "content": "The wet mixing time has been shown to influence the properties of an oxytetracycline dihydrate tablet formulation, wet granulated with PVP solution. Increased time of wet mixing produced larger, stronger and more dense granules, which compressed into tablets with longer disintegration and dissolution times. Decreased drug particle size aggravated these trends. A decrease in drug particle size also produced larger, stronger and more dense granules. Above an oxytetracycline mean particle diameter of about 6 mum, the tablet dissolution was satisfactory. As the oxytetracycline particle size was decreased further, however, the distintegration and dissolution of the corresponding tablets was markedly slower.", "contents": "Oxytetracycline tablet formulations: the effect of wet mixing time, particle size and batch variation on granule and tablet properties. The wet mixing time has been shown to influence the properties of an oxytetracycline dihydrate tablet formulation, wet granulated with PVP solution. Increased time of wet mixing produced larger, stronger and more dense granules, which compressed into tablets with longer disintegration and dissolution times. Decreased drug particle size aggravated these trends. A decrease in drug particle size also produced larger, stronger and more dense granules. Above an oxytetracycline mean particle diameter of about 6 mum, the tablet dissolution was satisfactory. As the oxytetracycline particle size was decreased further, however, the distintegration and dissolution of the corresponding tablets was markedly slower."}
{"id": "PMID:6714", "title": "Identification of monohydroxylated metabolites of cannabidiol formed by rat liver.", "content": "Cannabidiol (CBD) was metabolized in vitro by rat liver enzymes. Unchanged CBD and eight monohydroxylated metabolites were isolated and positively identified. As previously reported, 7-hydroxy-CBD was the major metabolite. The second most abundant metabolite was 6alpha-hydroxy-CBD; whereas only a trace amount of 6beta-hydroxy-CBD was found. In addition hydroxylation occurred in all positions of the pentyl side chain, 4 inches-hydroxy-CBD being most abundant. 3 inches-Hydroxy-CBD was formed in half of the yield of 4 inches-hydroxy-CBD, while 1 inches-, 2 inches-, 5 inches-hydroxy-CBD were each formed in approximately one fourth of the yield of 4 inches-hydroxy-CBD.", "contents": "Identification of monohydroxylated metabolites of cannabidiol formed by rat liver. Cannabidiol (CBD) was metabolized in vitro by rat liver enzymes. Unchanged CBD and eight monohydroxylated metabolites were isolated and positively identified. As previously reported, 7-hydroxy-CBD was the major metabolite. The second most abundant metabolite was 6alpha-hydroxy-CBD; whereas only a trace amount of 6beta-hydroxy-CBD was found. In addition hydroxylation occurred in all positions of the pentyl side chain, 4 inches-hydroxy-CBD being most abundant. 3 inches-Hydroxy-CBD was formed in half of the yield of 4 inches-hydroxy-CBD, while 1 inches-, 2 inches-, 5 inches-hydroxy-CBD were each formed in approximately one fourth of the yield of 4 inches-hydroxy-CBD."}
{"id": "PMID:6715", "title": "Characterization of the butyl homologues of delta1-tetrahydrocannabinol, cannabinol and cannabidiol in samples of cannabis by combined gas chromatography and mass spectrometry.", "content": "The butyl homologues of delta1-tetrahydrocannabinol, delta1-tetrahydrocannabinolic acid, cannabinol and cannabidiol have been identified in several samples of cannabis. 8 samples contained delta1-tetrahydrocannabinolic acid, one sample contained cannabinol and one sample contained both cannabinol and cannabidiol. Separation by gas chromatography and identification by gas chromotography-mass spectrometry was achieved by the preparation of trimethylsilyl, d9-trimethylsilyl, triethylsilyl and tri-n-propylsilyl derivatives.", "contents": "Characterization of the butyl homologues of delta1-tetrahydrocannabinol, cannabinol and cannabidiol in samples of cannabis by combined gas chromatography and mass spectrometry. The butyl homologues of delta1-tetrahydrocannabinol, delta1-tetrahydrocannabinolic acid, cannabinol and cannabidiol have been identified in several samples of cannabis. 8 samples contained delta1-tetrahydrocannabinolic acid, one sample contained cannabinol and one sample contained both cannabinol and cannabidiol. Separation by gas chromatography and identification by gas chromotography-mass spectrometry was achieved by the preparation of trimethylsilyl, d9-trimethylsilyl, triethylsilyl and tri-n-propylsilyl derivatives."}
{"id": "PMID:6716", "title": "Tremorine-oxotremorine-induced tremor, hypothermia and analgesia, and physostigmine toxicity, in mice after pretreatment with beta-adrenoceptor antagonists.", "content": "The beta-adrenoceptor blockers propranolol, PhQA33 and LB-46 exhibited appreciable activity against tremorine-(TMN) and oxotremorine-(OTMN) induced tremor, whereas pronethalol, (+)-H56/28, (-)-H56/28, K\u00f6-592 and L(+)-INPEA possessed weak action. The two beta-blockers, namely D,L(+/-)-INPEA and D(-)-INPEA acted as weak tremorgens. None of the above compounds suppressed the induced peripheral cholinergic phenomena; or possessed any central anticholinergic activity, as they were unable to afford protection against physostigmine-induced death. Propranolol, PhQA33 and LB-46 antagonized TMN-induced hypothermia and analgesia, but were inactive against OTMN-induced changes. A correlation of the beta-blocking and anti-tremor activity of these agents is unlikely.", "contents": "Tremorine-oxotremorine-induced tremor, hypothermia and analgesia, and physostigmine toxicity, in mice after pretreatment with beta-adrenoceptor antagonists. The beta-adrenoceptor blockers propranolol, PhQA33 and LB-46 exhibited appreciable activity against tremorine-(TMN) and oxotremorine-(OTMN) induced tremor, whereas pronethalol, (+)-H56/28, (-)-H56/28, K\u00f6-592 and L(+)-INPEA possessed weak action. The two beta-blockers, namely D,L(+/-)-INPEA and D(-)-INPEA acted as weak tremorgens. None of the above compounds suppressed the induced peripheral cholinergic phenomena; or possessed any central anticholinergic activity, as they were unable to afford protection against physostigmine-induced death. Propranolol, PhQA33 and LB-46 antagonized TMN-induced hypothermia and analgesia, but were inactive against OTMN-induced changes. A correlation of the beta-blocking and anti-tremor activity of these agents is unlikely."}
{"id": "PMID:6717", "title": "The isolated cremaster muscle preparation and (external) spermatic nerve-cremaster muscle preparation of the guinea-pig.", "content": "The isolated cremaster muscle preparation and spermatic nerve-cremaster muscle preparation of the guinea-pig were studied in vitro to determine their suitability as pharmacological test models. The preparation was contracted by acetylcholine, carbachol, succinylcholine and decamethonium (pD2 values, 4-2, 5-3, 7-3 and 7-4, respectively) through an action on a curare-sensitive cholinoceptor. Lobeline and DMPP were ineffective. Nicotine contracted the muscle, but there was tachyphylaxis. Tubocurarine and hexamethonium presumably competitively antagonized acetylcholine (pA2 values, 7-3 and 5-8); lobeline was a non-competitive antagonist (pD'2 value, 6-4). Atropine and mecamylamine exerted a dualistic action against acetylcholine (final pD'2 values, 5-3 and 6-7, respectively). Tubocurarine, succinylcholine and decamethonium exhibited their typical action when tested with spermatic nerve-cremaster muscle preparation; the latter two drugs also produced muscle spasm. Hexamethonium was a weak blocker of neuromuscular transmission. Atropine, mecamylamine, lobeline and DMPP exhibited neuromuscular blocking activity; however, directly evoked muscle twitches were also notably affected. The cremaster muscle preparations seem to add usefully to the list of currently used in vitro tests, with the added advantage that a mammalian skeletal muscle model is used for simultaneous quantitative studies.", "contents": "The isolated cremaster muscle preparation and (external) spermatic nerve-cremaster muscle preparation of the guinea-pig. The isolated cremaster muscle preparation and spermatic nerve-cremaster muscle preparation of the guinea-pig were studied in vitro to determine their suitability as pharmacological test models. The preparation was contracted by acetylcholine, carbachol, succinylcholine and decamethonium (pD2 values, 4-2, 5-3, 7-3 and 7-4, respectively) through an action on a curare-sensitive cholinoceptor. Lobeline and DMPP were ineffective. Nicotine contracted the muscle, but there was tachyphylaxis. Tubocurarine and hexamethonium presumably competitively antagonized acetylcholine (pA2 values, 7-3 and 5-8); lobeline was a non-competitive antagonist (pD'2 value, 6-4). Atropine and mecamylamine exerted a dualistic action against acetylcholine (final pD'2 values, 5-3 and 6-7, respectively). Tubocurarine, succinylcholine and decamethonium exhibited their typical action when tested with spermatic nerve-cremaster muscle preparation; the latter two drugs also produced muscle spasm. Hexamethonium was a weak blocker of neuromuscular transmission. Atropine, mecamylamine, lobeline and DMPP exhibited neuromuscular blocking activity; however, directly evoked muscle twitches were also notably affected. The cremaster muscle preparations seem to add usefully to the list of currently used in vitro tests, with the added advantage that a mammalian skeletal muscle model is used for simultaneous quantitative studies."}
{"id": "PMID:6718", "title": "Mediation of prostaglandin E2 in the biphasic response to ATP of the isolated tracheal muscle of guinea-pigs.", "content": "ATP, at a dose higher than 0-1 mug m1(-1), showed a biphasic action consisting of an initial increase followed by a gradual decrease of muscle tension in the isolated tracheal strip-chains of guinea-pigs. The pattern of this biphasic response to ATP varied with the level of basal tone of the preparation at the moment of application of ATP. A smiliar biphasic action was obtained by prostaglandin (PG) E2 among the various active substances studied including acetylcholine, histamine, catecholamines and various types of PG. Indomethacin (0-1 mug m1(-1) and aspirin (30 mug m1(-1)) completely abolished the ATP-induced inhibitory response observed in the presence of histamine (10 muM). Polyphloretin phosphate (100 mug m1(-1)) also significantly depressed the inhibitory response to ATP or PGE2. It is concluded that the response to ATP of the preparation is mediated by PGE2 released via the stimulation of its biosynthesis.", "contents": "Mediation of prostaglandin E2 in the biphasic response to ATP of the isolated tracheal muscle of guinea-pigs. ATP, at a dose higher than 0-1 mug m1(-1), showed a biphasic action consisting of an initial increase followed by a gradual decrease of muscle tension in the isolated tracheal strip-chains of guinea-pigs. The pattern of this biphasic response to ATP varied with the level of basal tone of the preparation at the moment of application of ATP. A smiliar biphasic action was obtained by prostaglandin (PG) E2 among the various active substances studied including acetylcholine, histamine, catecholamines and various types of PG. Indomethacin (0-1 mug m1(-1) and aspirin (30 mug m1(-1)) completely abolished the ATP-induced inhibitory response observed in the presence of histamine (10 muM). Polyphloretin phosphate (100 mug m1(-1)) also significantly depressed the inhibitory response to ATP or PGE2. It is concluded that the response to ATP of the preparation is mediated by PGE2 released via the stimulation of its biosynthesis."}
{"id": "PMID:6719", "title": "The effects of angiotensin I and angiotensin II on the isolated tracheal muscle of the cat.", "content": "The effects of Asp1-beta-amide-Val5-angiotensin II (A II) and Asp1-Ile5-angiotensin I (A I) have been studied on the isolated continuously superfused cat tracheal muscle contracted by 5-hydroxytryptamine (5-HT). Both peptides have been shown to induce dose-dependent relaxation on this muscle. Similar effects have been obtained with synthetic bradykinin, prostaglandin E2 (PGE2), noradrenaline and histamine. The effects of bradykinin, A I and A II have been shown to be inhibited by aspirin but not by propranolol, metiamide, SC 19220 or a specific, competitive antagonist of A II. The relaxing effect of A I is not due to the conversion of decapeptide to octapeptide A II. The possible mechanism of the relaxing effects of A I and A II on the cat isolated tracheal muscle is discussed.", "contents": "The effects of angiotensin I and angiotensin II on the isolated tracheal muscle of the cat. The effects of Asp1-beta-amide-Val5-angiotensin II (A II) and Asp1-Ile5-angiotensin I (A I) have been studied on the isolated continuously superfused cat tracheal muscle contracted by 5-hydroxytryptamine (5-HT). Both peptides have been shown to induce dose-dependent relaxation on this muscle. Similar effects have been obtained with synthetic bradykinin, prostaglandin E2 (PGE2), noradrenaline and histamine. The effects of bradykinin, A I and A II have been shown to be inhibited by aspirin but not by propranolol, metiamide, SC 19220 or a specific, competitive antagonist of A II. The relaxing effect of A I is not due to the conversion of decapeptide to octapeptide A II. The possible mechanism of the relaxing effects of A I and A II on the cat isolated tracheal muscle is discussed."}
{"id": "PMID:6720", "title": "Anticholinergic activity of antipsychotic drugs in relation to their extrapyramidal effects.", "content": "Antipsychotic drugs were evaluated with two indices of anticholinergic activity, mydriasis in mice in vivo and antagonism of carbamylcholine-induced contractions of guinea-pig tracheal strips in vitro. The drugs from most to least potent as oral mydriatic agents were mepazine, clozapine, thioridazine, promazine and chlorpromazine. Trifluoperazine, pimozide and haloperidol were inactive. These results were consistent with the hypothesis that anticholinergic activity of antipsychotic drugs is inversely related to their propensity to produce extrapyramidal effects in man. In vitro results appeared to predict the incidence of extraphyramidal effects less accurately than in vivo results.", "contents": "Anticholinergic activity of antipsychotic drugs in relation to their extrapyramidal effects. Antipsychotic drugs were evaluated with two indices of anticholinergic activity, mydriasis in mice in vivo and antagonism of carbamylcholine-induced contractions of guinea-pig tracheal strips in vitro. The drugs from most to least potent as oral mydriatic agents were mepazine, clozapine, thioridazine, promazine and chlorpromazine. Trifluoperazine, pimozide and haloperidol were inactive. These results were consistent with the hypothesis that anticholinergic activity of antipsychotic drugs is inversely related to their propensity to produce extrapyramidal effects in man. In vitro results appeared to predict the incidence of extraphyramidal effects less accurately than in vivo results."}
{"id": "PMID:6721", "title": "Some factors influencing dissolution from salicylic acid-urea solid dispersions.", "content": "Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained.", "contents": "Some factors influencing dissolution from salicylic acid-urea solid dispersions. Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained."}
{"id": "PMID:6747", "title": "Aggregation of antiacetylcholine drugs in aqueous solution: micellar properties of some diphenylmethane derivatives.", "content": "Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined.", "contents": "Aggregation of antiacetylcholine drugs in aqueous solution: micellar properties of some diphenylmethane derivatives. Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined."}
{"id": "PMID:6748", "title": "The crystallization behaviour of sulphathiazole.", "content": "Previous investigations into the dissolution kinetics of sulphathiazole Form 1 have shown the process to be first order with respect to driving force. However, below 37 degrees first order kinetics did not apply, due to the surface reaction becoming the rate controlling factor. The present study examines the kinetics of crystallization over the temperature range 25 to 50 degrees. Crystallization is a process greatly dependent upon the high-entropy surface integration step which, unlike the dissolution process, is much more sensitive to crystal growth inhibitors. In the absence of inhibitors crystallization above 34 degrees follows first order kinetics but below 34 degrees the process changes to third order. Similar temperature effects on the dissolution of sulphathiazole have been previously reported.", "contents": "The crystallization behaviour of sulphathiazole. Previous investigations into the dissolution kinetics of sulphathiazole Form 1 have shown the process to be first order with respect to driving force. However, below 37 degrees first order kinetics did not apply, due to the surface reaction becoming the rate controlling factor. The present study examines the kinetics of crystallization over the temperature range 25 to 50 degrees. Crystallization is a process greatly dependent upon the high-entropy surface integration step which, unlike the dissolution process, is much more sensitive to crystal growth inhibitors. In the absence of inhibitors crystallization above 34 degrees follows first order kinetics but below 34 degrees the process changes to third order. Similar temperature effects on the dissolution of sulphathiazole have been previously reported."}
{"id": "PMID:6749", "title": "Anomalies in some properties of powder mixtures.", "content": "Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures.", "contents": "Anomalies in some properties of powder mixtures. Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures."}
{"id": "PMID:6750", "title": "Fluorimetric assay of tetracycline mixtures.", "content": "A simple and precise fluorimetric method is described for the simultaneous assay in plasma of a mixture containing chlortetracycline, demethylchlortetracycline and tetracycline. Assay within the therapeutic ranges of 0-5 mg litre(-1) is achieved by formation of strongly fluorescent aluminum/tetracycline complexes, without prior extraction or separation of the individual antibiotics. This is performed by determinations at the peak excitation and fluorescence emission wavelengths of each tetracycline chelate. The method can be similarly applied to the assay of oxytetracycline, rolitetracycline and minocycline.", "contents": "Fluorimetric assay of tetracycline mixtures. A simple and precise fluorimetric method is described for the simultaneous assay in plasma of a mixture containing chlortetracycline, demethylchlortetracycline and tetracycline. Assay within the therapeutic ranges of 0-5 mg litre(-1) is achieved by formation of strongly fluorescent aluminum/tetracycline complexes, without prior extraction or separation of the individual antibiotics. This is performed by determinations at the peak excitation and fluorescence emission wavelengths of each tetracycline chelate. The method can be similarly applied to the assay of oxytetracycline, rolitetracycline and minocycline."}
{"id": "PMID:6751", "title": "Preliminary investigations of the metabolism and pharmacological activity of beta-hydroxytryptamines in mammals.", "content": "beta-Hydroxytryptamine and beta-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of beta-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines nonhydroxylated in the side chain. The pharmacological activities of beta-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was beta-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same.", "contents": "Preliminary investigations of the metabolism and pharmacological activity of beta-hydroxytryptamines in mammals. beta-Hydroxytryptamine and beta-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of beta-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines nonhydroxylated in the side chain. The pharmacological activities of beta-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was beta-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same."}
{"id": "PMID:6752", "title": "Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system.", "content": "In gallamine-immobilized cats, the caudate nucleus and the nucleus accumbens septi were perfused by means of a push-pull cannula and dopamine was measured in the perfusate. Chlorpromazine (10 mg kg(-1)) and clozapine (20 mg kg(-1)), administered intravenously, enhanced the release of dopamine. The effect of chlorpromazine was similar in both regions whereas that of clozapine was more pronounced in the nucleus accumbens than in the caudate nucleus. Furthermore, in the rat, sulpiride, clozapine and thioridazine increased the homovanillic acid concentration in striatum and limbic system to a similar extent. However, following probenecid administration, the net effect of these drugs on homovanillic acid accumulation was more marked in the limbic system than in the striatum whereas haolperidol and chlorpromazine had a similar effect in the two regions. It is concluded that, in contrast to haloperidol and chlorpromazine, sulpiride, clozapine and thioridazine may preferentially affect the limbic dopaminergic transmission. This possibly accounts for the fact that sulpiride, clozapine and thioridazine display an antipsychotic action and yet cause less extrapyramidal side effects than haloperidol and chlorpromazine.", "contents": "Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. In gallamine-immobilized cats, the caudate nucleus and the nucleus accumbens septi were perfused by means of a push-pull cannula and dopamine was measured in the perfusate. Chlorpromazine (10 mg kg(-1)) and clozapine (20 mg kg(-1)), administered intravenously, enhanced the release of dopamine. The effect of chlorpromazine was similar in both regions whereas that of clozapine was more pronounced in the nucleus accumbens than in the caudate nucleus. Furthermore, in the rat, sulpiride, clozapine and thioridazine increased the homovanillic acid concentration in striatum and limbic system to a similar extent. However, following probenecid administration, the net effect of these drugs on homovanillic acid accumulation was more marked in the limbic system than in the striatum whereas haolperidol and chlorpromazine had a similar effect in the two regions. It is concluded that, in contrast to haloperidol and chlorpromazine, sulpiride, clozapine and thioridazine may preferentially affect the limbic dopaminergic transmission. This possibly accounts for the fact that sulpiride, clozapine and thioridazine display an antipsychotic action and yet cause less extrapyramidal side effects than haloperidol and chlorpromazine."}
{"id": "PMID:6753", "title": "An in vitro method for the study of beta-receptor mediated effects on slow contracting skeletal muscle.", "content": "The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0.5 ms pulses at 10-12 Hz for 1.5 or 3 s every 22 s). The experiments were performed at 37 degrees. Terbutaline, a selective agonist at beta2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0.2 muM. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies.", "contents": "An in vitro method for the study of beta-receptor mediated effects on slow contracting skeletal muscle. The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0.5 ms pulses at 10-12 Hz for 1.5 or 3 s every 22 s). The experiments were performed at 37 degrees. Terbutaline, a selective agonist at beta2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0.2 muM. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies."}
{"id": "PMID:6754", "title": "Effects of alpha-methyldopa on blood pressure in the anaesthetized dog.", "content": "Intravenous infusion over 1 h of 20 mg kg(-1) of alpha-methyldopa produced hypotension in the anaesthetized dog. The magnitude of this effect was, however, inversely correlated with bodyweight. Either rapid intravenous injection of alpha-methyldopa or slow infusion of alpha-methyldopate, was less effective in lowering blood pressure than infusion of free alpha methyldopa in dogs of equivalent bodyweight. Infusion of alpha-methyldopa into a vertebral or internal carotid artery produced hypotensive responses but these were no greater and generally less than those obtained to intravenous infusion. alpha-Methyldopa was therefore capable of producing hypotension in the dog but no evidence was obtained for this being the result of an action within the brain.", "contents": "Effects of alpha-methyldopa on blood pressure in the anaesthetized dog. Intravenous infusion over 1 h of 20 mg kg(-1) of alpha-methyldopa produced hypotension in the anaesthetized dog. The magnitude of this effect was, however, inversely correlated with bodyweight. Either rapid intravenous injection of alpha-methyldopa or slow infusion of alpha-methyldopate, was less effective in lowering blood pressure than infusion of free alpha methyldopa in dogs of equivalent bodyweight. Infusion of alpha-methyldopa into a vertebral or internal carotid artery produced hypotensive responses but these were no greater and generally less than those obtained to intravenous infusion. alpha-Methyldopa was therefore capable of producing hypotension in the dog but no evidence was obtained for this being the result of an action within the brain."}
{"id": "PMID:6755", "title": "The effect of cholinesterase inhibitors on the antimuscarinic effect of hemicholinium-3 (HC-3) in the rat.", "content": "The effect of hemicholinium-3 (HC-3) on responses of the rat isolated bladder and ileum to acetylcholine and carbachol was investigated in the absence and presence of a number of anticholinesterases. Responses of the bladder to acetylcholine were potentiated by DFP, edrophonium, BW284C51 and physostigmine but were unaffected by the specific butyrylcholinesterase inhibitor iso-OMPA. Responses to carbachol were not potentiated by the anticholinesterases. HC-3 (1.7 X 10(-4) M) inhibited responses to carbachol without affecting those to acetylcholine. In the presence of physostigmine or DFP responses to acetylcholine were inhibited by HC-3 but no such inhibition was observed in the presence of BW284C51, edrophonium or iso-OMPA or a combination of the latter two anticholinesterases. Responses to carbachol were also inhibited to a greater extent in the presence of DFP. In the ileum, responses to acetylcholine were increased in the presence of DFP, edrophonium and physostigmine but were unaffected by iso-Ompa. responses to carbachol were not increased by any of the anticholinesterases. HC-3 (2.8 X 10(-4) M) inhibited responses to both acetylcholine and carbachol in the ileum and the degree of inhibition was not significantly altered by the presence of any of the anticholinesterases used. Although a weak anticholinesterase, HC-3 was also found to decrease the inhibitory action of physostigmine on the hydrolysis of acetylcholine by homogenates of rat ileum. A similar effect was noted with DFP but not with edrophonium. The results obtained do not support a prejunctional action for HC-3 in antagonizing responses to carbachol. It is concluded that in addition to an inhibitory action on the post-junctional muscarinic receptor HC-3 may interfere with the anticholinesterase activity of some cholinesterase inhibitors such as physostigmine and DFP but not edrophonium.", "contents": "The effect of cholinesterase inhibitors on the antimuscarinic effect of hemicholinium-3 (HC-3) in the rat. The effect of hemicholinium-3 (HC-3) on responses of the rat isolated bladder and ileum to acetylcholine and carbachol was investigated in the absence and presence of a number of anticholinesterases. Responses of the bladder to acetylcholine were potentiated by DFP, edrophonium, BW284C51 and physostigmine but were unaffected by the specific butyrylcholinesterase inhibitor iso-OMPA. Responses to carbachol were not potentiated by the anticholinesterases. HC-3 (1.7 X 10(-4) M) inhibited responses to carbachol without affecting those to acetylcholine. In the presence of physostigmine or DFP responses to acetylcholine were inhibited by HC-3 but no such inhibition was observed in the presence of BW284C51, edrophonium or iso-OMPA or a combination of the latter two anticholinesterases. Responses to carbachol were also inhibited to a greater extent in the presence of DFP. In the ileum, responses to acetylcholine were increased in the presence of DFP, edrophonium and physostigmine but were unaffected by iso-Ompa. responses to carbachol were not increased by any of the anticholinesterases. HC-3 (2.8 X 10(-4) M) inhibited responses to both acetylcholine and carbachol in the ileum and the degree of inhibition was not significantly altered by the presence of any of the anticholinesterases used. Although a weak anticholinesterase, HC-3 was also found to decrease the inhibitory action of physostigmine on the hydrolysis of acetylcholine by homogenates of rat ileum. A similar effect was noted with DFP but not with edrophonium. The results obtained do not support a prejunctional action for HC-3 in antagonizing responses to carbachol. It is concluded that in addition to an inhibitory action on the post-junctional muscarinic receptor HC-3 may interfere with the anticholinesterase activity of some cholinesterase inhibitors such as physostigmine and DFP but not edrophonium."}
{"id": "PMID:6771", "title": "Rapid and sensitive colorimetric determination of cobalt(II).", "content": "A highly selective and sensitive spectrophotometric determination of cobalt (II) was developed. 7-Nitroso-8-hydroxyquinoline-5-sulfonic acid sodium salt was used as the chromogenic reagent for color development. Although other metals form colored chelates with the ligand, it was possible to develop a selective method using McIlvaine's pH 8 citric acid-phosphate buffer. Under these conditions, iron(II), iron (III), copper (II), zinc (II), and manganese (II), minerals likely to be compounded with cobalt (II) in geriatric formulations, do not interfere with the precision of the method or the color development. Calcium (II) and magnesium (II) do not form colored chelates with the used ligand. Hormones, vitamins, and additives likely to be present along with the cobalt ion in pharmaceutical formulations do not interfere. The sensitivity is 0.37 mug of cobalt (II)/ml of sample solution.", "contents": "Rapid and sensitive colorimetric determination of cobalt(II). A highly selective and sensitive spectrophotometric determination of cobalt (II) was developed. 7-Nitroso-8-hydroxyquinoline-5-sulfonic acid sodium salt was used as the chromogenic reagent for color development. Although other metals form colored chelates with the ligand, it was possible to develop a selective method using McIlvaine's pH 8 citric acid-phosphate buffer. Under these conditions, iron(II), iron (III), copper (II), zinc (II), and manganese (II), minerals likely to be compounded with cobalt (II) in geriatric formulations, do not interfere with the precision of the method or the color development. Calcium (II) and magnesium (II) do not form colored chelates with the used ligand. Hormones, vitamins, and additives likely to be present along with the cobalt ion in pharmaceutical formulations do not interfere. The sensitivity is 0.37 mug of cobalt (II)/ml of sample solution."}
{"id": "PMID:6772", "title": "High-pressure liquid chromatographic determination of the 15-epimer of dinoprost in bulk drug.", "content": "The p-nitrophenacyl esters of dinoprost and its 15-epimer are well resolved using high-pressure liquid chromatography. Quantitation was achieved using the internal standard technique. The specially synthesized diphenylurea ester of cholic acid was found to be a model internal standard. Graphs of peak height ratios of the prostaglandin to the internal standard were linear with respect to the amount of prostaglandin injected, with the lower detection limit of the 15-epimer being about 0.5%. Data are presented that demonstrate the usefulness of this analytical technique in determining the concentration of the 15-epimer present during studies on the kinetics of decomposition of dinoprost.", "contents": "High-pressure liquid chromatographic determination of the 15-epimer of dinoprost in bulk drug. The p-nitrophenacyl esters of dinoprost and its 15-epimer are well resolved using high-pressure liquid chromatography. Quantitation was achieved using the internal standard technique. The specially synthesized diphenylurea ester of cholic acid was found to be a model internal standard. Graphs of peak height ratios of the prostaglandin to the internal standard were linear with respect to the amount of prostaglandin injected, with the lower detection limit of the 15-epimer being about 0.5%. Data are presented that demonstrate the usefulness of this analytical technique in determining the concentration of the 15-epimer present during studies on the kinetics of decomposition of dinoprost."}
{"id": "PMID:6773", "title": "Effect of edetate disodium and reduced glutathione on absorption of acetazolamide from GI tract of rats.", "content": "The absorption of acetazolamide suspensions from in situ rat gastric and intestinal loop segments was studied. In 1 hr, 66.2 and 64.3% remained unabsorbed from the rat stomach and intestine, respectively. Although 1% (w/v) reduced glutathione and 1% (w/v) (24 mM) edetate disodium had no effect on gastric absorption, drug absorption from the rat intestine (1 hr) was increased 1.5 and 2 times, respectively. It was hypothesized that the relatively poor intestinal absorption was due primarily to the formation of a pH-dependent (pH 4.5-10), nonabsorbable complex between acetazolamide and carbonic anhydrase present in the gut and that reduced glutathione acted as an inhibitor to promote intestinal absorption. Equilibrium dialysis studies showed that reduced glutathion could reduce the fraction of drug bound to human carbonic anhydrase B by one-half when present in a molar ratio 10 times that of acetazolamide; edetate disodium had no effect on the in vitro binding. It was, therefore, assumed that edetate disodium promoted an increase in intestinal absorption by altering the permeability of intestinal epithelium. Based upon present experimentation, however, the alteration of intestinal epithelium by reduced glutathione cannot be ruled out.", "contents": "Effect of edetate disodium and reduced glutathione on absorption of acetazolamide from GI tract of rats. The absorption of acetazolamide suspensions from in situ rat gastric and intestinal loop segments was studied. In 1 hr, 66.2 and 64.3% remained unabsorbed from the rat stomach and intestine, respectively. Although 1% (w/v) reduced glutathione and 1% (w/v) (24 mM) edetate disodium had no effect on gastric absorption, drug absorption from the rat intestine (1 hr) was increased 1.5 and 2 times, respectively. It was hypothesized that the relatively poor intestinal absorption was due primarily to the formation of a pH-dependent (pH 4.5-10), nonabsorbable complex between acetazolamide and carbonic anhydrase present in the gut and that reduced glutathione acted as an inhibitor to promote intestinal absorption. Equilibrium dialysis studies showed that reduced glutathion could reduce the fraction of drug bound to human carbonic anhydrase B by one-half when present in a molar ratio 10 times that of acetazolamide; edetate disodium had no effect on the in vitro binding. It was, therefore, assumed that edetate disodium promoted an increase in intestinal absorption by altering the permeability of intestinal epithelium. Based upon present experimentation, however, the alteration of intestinal epithelium by reduced glutathione cannot be ruled out."}
{"id": "PMID:6774", "title": "Chlorpromazine metabolism VIII: blood levels of chlorpromazine and its sulfoxide in schizophrenic patients.", "content": "A procedure was standardized for extracting chloropromazine and its sulfoxide from the blood and for applying a recently developed fluorometric assay method to determine blood levels of these two compounds in schizophrenic patients receiving chlorpromazine therapy. The described methodology opens avenues for performing bioavailability and generic equivalence studies in humans.", "contents": "Chlorpromazine metabolism VIII: blood levels of chlorpromazine and its sulfoxide in schizophrenic patients. A procedure was standardized for extracting chloropromazine and its sulfoxide from the blood and for applying a recently developed fluorometric assay method to determine blood levels of these two compounds in schizophrenic patients receiving chlorpromazine therapy. The described methodology opens avenues for performing bioavailability and generic equivalence studies in humans."}
{"id": "PMID:6775", "title": "Effects of various hydrodynamic conditions on dissolution rate determinations.", "content": "An automated potentiometric procedure was used in dissolution rate studies to determine the effects of various hydrodynamic conditions on dissolution rate determinations. Changes in the hydrodynamics of the system resulted from using various sizes and shapes of dissolution vessels. Dissolution rate constants for benzoic acid prills in distilled water at pH-stat 6.2 were used as a measure of the agitation intensities present in the different shaped vessels. Great variations in the dissolution rates occurred in vessels with the same diameter and stirrer blade position when the shapes of the bottom of the vessel were varied. A similar order of dissolution rates was obtained at 100 and 150 rpm for the individual vessels at various propeller heights. The order differed from one vessel to another, depending on the shape of the bottom (concave, convex, or flat) of the vessel. In some cases, a change in the type of bottom resulted in the opposite order of rates for vessels with the same diameter.", "contents": "Effects of various hydrodynamic conditions on dissolution rate determinations. An automated potentiometric procedure was used in dissolution rate studies to determine the effects of various hydrodynamic conditions on dissolution rate determinations. Changes in the hydrodynamics of the system resulted from using various sizes and shapes of dissolution vessels. Dissolution rate constants for benzoic acid prills in distilled water at pH-stat 6.2 were used as a measure of the agitation intensities present in the different shaped vessels. Great variations in the dissolution rates occurred in vessels with the same diameter and stirrer blade position when the shapes of the bottom of the vessel were varied. A similar order of dissolution rates was obtained at 100 and 150 rpm for the individual vessels at various propeller heights. The order differed from one vessel to another, depending on the shape of the bottom (concave, convex, or flat) of the vessel. In some cases, a change in the type of bottom resulted in the opposite order of rates for vessels with the same diameter."}
{"id": "PMID:6776", "title": "Determination of tinidazole in tablets by dc polarography.", "content": "A polarographic method was developed for determining tinidazole in tablets. The substance is extracted from the sample with water, pH 6.8 Britton-Robinson buffer is added to an aliquot, and the solution is polarographed at the dropping mercury electrode versus the saturated calomel electrode. The polarographic wave is well developed and enables a fairly precise quantitative determination. The method of standard addition is used.", "contents": "Determination of tinidazole in tablets by dc polarography. A polarographic method was developed for determining tinidazole in tablets. The substance is extracted from the sample with water, pH 6.8 Britton-Robinson buffer is added to an aliquot, and the solution is polarographed at the dropping mercury electrode versus the saturated calomel electrode. The polarographic wave is well developed and enables a fairly precise quantitative determination. The method of standard addition is used."}
{"id": "PMID:6777", "title": "Spectrophotometric determination of diphenhydramine hydrochloride using dipicrylamine.", "content": "A spectrophotometric procedure for the determination of diphenhydramine hydrochloride based on the reaction with dipicrylamine was developed. A yellow complex forms and is easily extractable by chloroform at pH 5. The mole ratio of diphenydramine hydrochloride to dipicrylamine in the complex is 1:3. The absorbance of the complex obeys Beer's law over the concentration range of 3-10 mug of diphenhydramine hydrochloride per ml of chloroform. This procedure can be carried out in the presence of other compounds without interference.", "contents": "Spectrophotometric determination of diphenhydramine hydrochloride using dipicrylamine. A spectrophotometric procedure for the determination of diphenhydramine hydrochloride based on the reaction with dipicrylamine was developed. A yellow complex forms and is easily extractable by chloroform at pH 5. The mole ratio of diphenydramine hydrochloride to dipicrylamine in the complex is 1:3. The absorbance of the complex obeys Beer's law over the concentration range of 3-10 mug of diphenhydramine hydrochloride per ml of chloroform. This procedure can be carried out in the presence of other compounds without interference."}
{"id": "PMID:6778", "title": "Application of trihydroxyindole reaction to methanesulfonanilides: fluorometric analysis for soterenol and mesuprine.", "content": "Methanesulfonanilides, like soterenol and mesuprine, which are bioisosteric with adrenergic catecholamines, form fluorescent species when subjected to the trihydroxyindole reaction. Presumably, the fluorescence is due to adrenolutin-like species formed from aminochrome intermediates. Fluorescence was not induced in a relative of soterenol where a methyl group was added to the sulfonamido nitrogen, a fact that suggests the presence of a quinoid intermediate in the reaction scheme of soterenol. A ring isomer of soterenol, where the methanesulfonamido and hydroxyl groups were interchanged, produced only about 5% as much fluorescence response as soterenol. The sterenol counterparts to isoproterenol and isoproterenol sulfonic acid did not produce fluorescence when treated like soterenol. This finding and the fact that response was linear with concentration for soterenol and mesuprine suggest that a fluorometric analysis could be developed for these methanesulfonanilides.", "contents": "Application of trihydroxyindole reaction to methanesulfonanilides: fluorometric analysis for soterenol and mesuprine. Methanesulfonanilides, like soterenol and mesuprine, which are bioisosteric with adrenergic catecholamines, form fluorescent species when subjected to the trihydroxyindole reaction. Presumably, the fluorescence is due to adrenolutin-like species formed from aminochrome intermediates. Fluorescence was not induced in a relative of soterenol where a methyl group was added to the sulfonamido nitrogen, a fact that suggests the presence of a quinoid intermediate in the reaction scheme of soterenol. A ring isomer of soterenol, where the methanesulfonamido and hydroxyl groups were interchanged, produced only about 5% as much fluorescence response as soterenol. The sterenol counterparts to isoproterenol and isoproterenol sulfonic acid did not produce fluorescence when treated like soterenol. This finding and the fact that response was linear with concentration for soterenol and mesuprine suggest that a fluorometric analysis could be developed for these methanesulfonanilides."}
{"id": "PMID:6779", "title": "Continuous dissolution rate determination as a function of the pH of the medium.", "content": "A method was developed for varying the pH of the medium during dissolution rate studies of timed-release tablets with the aid of compressed, totally soluble, alkaline powder mixtures. Commercial as well as experimental timed-release capsules or tablets were used as models, and dissolution rates were determined at pH 1.1, 2.4, and 7.4. The system can be applied to other pH values or other variations of the dissolution medium (e.g., ionic strength) to: (a) correlate in vitro release rates with bioavailability data, (b) discriminate between alternative formulations during dosage form development, or (c) serve as a selective control procedure for a series of sustanined-release dosage forms.", "contents": "Continuous dissolution rate determination as a function of the pH of the medium. A method was developed for varying the pH of the medium during dissolution rate studies of timed-release tablets with the aid of compressed, totally soluble, alkaline powder mixtures. Commercial as well as experimental timed-release capsules or tablets were used as models, and dissolution rates were determined at pH 1.1, 2.4, and 7.4. The system can be applied to other pH values or other variations of the dissolution medium (e.g., ionic strength) to: (a) correlate in vitro release rates with bioavailability data, (b) discriminate between alternative formulations during dosage form development, or (c) serve as a selective control procedure for a series of sustanined-release dosage forms."}
{"id": "PMID:6780", "title": "Controlled flocculation of coarse suspensions by colloidally dispersed solids I: Interaction of bismuth subnitrate with bentonite.", "content": "Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate suspensions was achieved by the addition of small amounts of bentonite. The interaction of the coarse, positively charge bismuth subnitrate particles in aqueous suspension with negatively charged, colloidally dispersed bentonite was investigated by measuring electrophoretic mobility, sedimentation volume, and viscosity. Gradual addition of bentonite dispersion to bismuth subnitrate suspensions first reduced the zeta-potential of the bismuth subnitrate particles from +28 mv to zero, then inverted it, and finally caused it to level off at -20 mv for bismuth subnitrate-bentonite weight ratios below 200. Owing to the much greater specific surface area of bentonite, the surface of the bismuth subnitrate lath-shaped crystals was completely covered by 0.5% of its weight in clay platelets. Adhesion was promoted by electrovalences between surface bismuthyl ions and cation-exchange sites of the clay and by secondary valences. The charge neutralization of bismuth subnitrate by bentonite was a heterocoagulation process: the addition of small amounts of the clay flocculated the bismuth subnitrate suspensions and eliminated caking. While the zeta-potential of the bismuth subnitrate particles leveled off when their surface was saturated with bentonite platelets, sedimentation volume and viscosity continued to increase when the clay concentration was increased further while maintaining the bismuth subnitrate concentration constant. The excess, nonadsorbed bentonite formed the characteristic house-of-cards structure, incorporating the bentonite-coated bismuth subnitrate particles as cornerstones.", "contents": "Controlled flocculation of coarse suspensions by colloidally dispersed solids I: Interaction of bismuth subnitrate with bentonite. Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate suspensions was achieved by the addition of small amounts of bentonite. The interaction of the coarse, positively charge bismuth subnitrate particles in aqueous suspension with negatively charged, colloidally dispersed bentonite was investigated by measuring electrophoretic mobility, sedimentation volume, and viscosity. Gradual addition of bentonite dispersion to bismuth subnitrate suspensions first reduced the zeta-potential of the bismuth subnitrate particles from +28 mv to zero, then inverted it, and finally caused it to level off at -20 mv for bismuth subnitrate-bentonite weight ratios below 200. Owing to the much greater specific surface area of bentonite, the surface of the bismuth subnitrate lath-shaped crystals was completely covered by 0.5% of its weight in clay platelets. Adhesion was promoted by electrovalences between surface bismuthyl ions and cation-exchange sites of the clay and by secondary valences. The charge neutralization of bismuth subnitrate by bentonite was a heterocoagulation process: the addition of small amounts of the clay flocculated the bismuth subnitrate suspensions and eliminated caking. While the zeta-potential of the bismuth subnitrate particles leveled off when their surface was saturated with bentonite platelets, sedimentation volume and viscosity continued to increase when the clay concentration was increased further while maintaining the bismuth subnitrate concentration constant. The excess, nonadsorbed bentonite formed the characteristic house-of-cards structure, incorporating the bentonite-coated bismuth subnitrate particles as cornerstones."}
{"id": "PMID:6781", "title": "Urinary excretion of probenecid and its metabolites in humans as a function of dose.", "content": "A GLC assay was used to study the excretion of probenecid and its metabolites in the urine of human subjects following oral doses of 0.5, 1, and 2 g. From 75 to 88% of the  dose was found in the urine. The major metabolite, probenecid acyl glucuronide, accounted for 34-47% of the dose. Approximately equal amounts (10-15%) of the mono-N-propyl, secondary alcohol, and carboxylic acid metabolites were excreted in the unconjugated from with only traces in the conjugated form. The primary alcohol metabolite was not found in measurable amounts. The terminal half-lives for excretion of all metabolites were in the range of 4-6 hr, were independent of dose, and were limited by their rates of formation. A prolonged time course of excretion of the metabolites, particularly at higher doses, suggests that probenecid, being poorly soluble in water, precipitates from solution in the GI tract, forming a depot of drug from which absorption is dissolution rate limited. The urinary excretion of unchanged probenecid, which accounts for 4-13% of the dose, is dependent on both the pH and flow rate of urine.", "contents": "Urinary excretion of probenecid and its metabolites in humans as a function of dose. A GLC assay was used to study the excretion of probenecid and its metabolites in the urine of human subjects following oral doses of 0.5, 1, and 2 g. From 75 to 88% of the  dose was found in the urine. The major metabolite, probenecid acyl glucuronide, accounted for 34-47% of the dose. Approximately equal amounts (10-15%) of the mono-N-propyl, secondary alcohol, and carboxylic acid metabolites were excreted in the unconjugated from with only traces in the conjugated form. The primary alcohol metabolite was not found in measurable amounts. The terminal half-lives for excretion of all metabolites were in the range of 4-6 hr, were independent of dose, and were limited by their rates of formation. A prolonged time course of excretion of the metabolites, particularly at higher doses, suggests that probenecid, being poorly soluble in water, precipitates from solution in the GI tract, forming a depot of drug from which absorption is dissolution rate limited. The urinary excretion of unchanged probenecid, which accounts for 4-13% of the dose, is dependent on both the pH and flow rate of urine."}
{"id": "PMID:6782", "title": "Nitrofurantoin solubility in aqueous urea and creatinine solutions.", "content": "Experiments were carried out to determine the effect of urea and creatinine on the solubility of nitrofurantoin in water at different temperature and pH conditions. The addition of urea to aqueous media increased nitrofurantoin solubility up to a maximum concentration level and then decreased solubility at higher urea concentrations. The amount of urea needed to bring about maximum nitrofurantoin solubility was dependent on temperature and ranged between 1.75 and 2.50%. Spectral studies suggest a possible interaction between urea and nitrofurantoin molecules. Nitrofurantoin solubility increased with an increasing creatinine concentration ranging from 0.05 to 1.6%. Spectral studies indicate a strong interaction between creatinine and nitrofurantoin molecules in solution. The combined effect of urea and creatinine of the solubility of nitrofurantoin could account for the absence of crystalluria with this drug, even though unusually high concentrations in urine have been reported.", "contents": "Nitrofurantoin solubility in aqueous urea and creatinine solutions. Experiments were carried out to determine the effect of urea and creatinine on the solubility of nitrofurantoin in water at different temperature and pH conditions. The addition of urea to aqueous media increased nitrofurantoin solubility up to a maximum concentration level and then decreased solubility at higher urea concentrations. The amount of urea needed to bring about maximum nitrofurantoin solubility was dependent on temperature and ranged between 1.75 and 2.50%. Spectral studies suggest a possible interaction between urea and nitrofurantoin molecules. Nitrofurantoin solubility increased with an increasing creatinine concentration ranging from 0.05 to 1.6%. Spectral studies indicate a strong interaction between creatinine and nitrofurantoin molecules in solution. The combined effect of urea and creatinine of the solubility of nitrofurantoin could account for the absence of crystalluria with this drug, even though unusually high concentrations in urine have been reported."}
{"id": "PMID:6783", "title": "Influence of pH and route of injection on acute toxicity of tetracycline in mice.", "content": "Some LD50 determinations for tetracycline hydrochloride in mice were carried out over a range of pH values, using both the intraperitoneal and the subcutaneous routes of injection. Depending on the pH of the formulation, either water or a solvent system of water and 60% (v/v) propylene glycol was employed thus ensuring complete solution of the drug at all pH values tested. Higher LD50 values were obtained with the subcutaneous route than with the intraperitoneal route. With either route of administration, there was a trend toward lowest LD50 value occurrence at the isoelectric pH of tetracycline. Actual statistical significance was achieved for the intraperitoneal route only when LD50 values obtained at the isoelectric pH were compared with either of the more acidic pH values.", "contents": "Influence of pH and route of injection on acute toxicity of tetracycline in mice. Some LD50 determinations for tetracycline hydrochloride in mice were carried out over a range of pH values, using both the intraperitoneal and the subcutaneous routes of injection. Depending on the pH of the formulation, either water or a solvent system of water and 60% (v/v) propylene glycol was employed thus ensuring complete solution of the drug at all pH values tested. Higher LD50 values were obtained with the subcutaneous route than with the intraperitoneal route. With either route of administration, there was a trend toward lowest LD50 value occurrence at the isoelectric pH of tetracycline. Actual statistical significance was achieved for the intraperitoneal route only when LD50 values obtained at the isoelectric pH were compared with either of the more acidic pH values."}
{"id": "PMID:6784", "title": "Monoamine oxidase inhibition and the induction of ponto-geniculo-occipital wave activity by reserpine in the cat.", "content": "Reserpine induces ponto-geniculo-occipital wave activity similar to that seen in the cat during the rapid eye movement phase of sleep. This action of reserpine was blocked by the monoamine oxidase inhibitors, pheniprazine, harmaline and clorgyline, but not deprenyl or its demethylated analog. After a single dose (20 mg/kg) of either pheniprazine or harmaline, the time course of antagonism of the effect of reserpine was in good correspondence with inhibition of monoamine oxidase but not with restoration of the serotonin content of several regions of the brain. Harmaline had a reversible effect while that of pheniprazine persisted for weeks. Clorgyline in low doses (0.5-1.0 mg/kg), at which it is a specific inhibitor of type A monoamine oxidase, antagonized the action of reserpine for over 2 weeks. Deprenyl and its demethylated analog failed to suppress the reserpine-induced waves even at 10 times the dose of clorgyline when they should have completely inhibited type B monoamine oxidase. In contrast to antagonism of reserpine, suppression of rapid eye movement sleep by these monoamine oxidase inhibitors could be temporally dissociated from their inhibition of the enzyme. It is concluded that suppression of the induction of ponto-geniculo-occipital waves by reserpine after administration of the monoamine oxidase inhibitors is a specific effect of these drugs and is related to inhibition of type A monoamine oxidase. Suppression of rapid eye movement sleep is probably a nonspecific effect and not related to inhibition of the enzyme.", "contents": "Monoamine oxidase inhibition and the induction of ponto-geniculo-occipital wave activity by reserpine in the cat. Reserpine induces ponto-geniculo-occipital wave activity similar to that seen in the cat during the rapid eye movement phase of sleep. This action of reserpine was blocked by the monoamine oxidase inhibitors, pheniprazine, harmaline and clorgyline, but not deprenyl or its demethylated analog. After a single dose (20 mg/kg) of either pheniprazine or harmaline, the time course of antagonism of the effect of reserpine was in good correspondence with inhibition of monoamine oxidase but not with restoration of the serotonin content of several regions of the brain. Harmaline had a reversible effect while that of pheniprazine persisted for weeks. Clorgyline in low doses (0.5-1.0 mg/kg), at which it is a specific inhibitor of type A monoamine oxidase, antagonized the action of reserpine for over 2 weeks. Deprenyl and its demethylated analog failed to suppress the reserpine-induced waves even at 10 times the dose of clorgyline when they should have completely inhibited type B monoamine oxidase. In contrast to antagonism of reserpine, suppression of rapid eye movement sleep by these monoamine oxidase inhibitors could be temporally dissociated from their inhibition of the enzyme. It is concluded that suppression of the induction of ponto-geniculo-occipital waves by reserpine after administration of the monoamine oxidase inhibitors is a specific effect of these drugs and is related to inhibition of type A monoamine oxidase. Suppression of rapid eye movement sleep is probably a nonspecific effect and not related to inhibition of the enzyme."}
{"id": "PMID:6785", "title": "Further studies on angiotensin tachyphylaxis.", "content": "Rabbit aorta and rat fundus do not display tachyphylaxis to angiotensin II (Asp1)angiotensin II) at 37 degrees C. These tissues do, however, display tachyphylaxis to [Sar1]angiotensin II (N-methylglycine 1 angiotensin II) and [dimethylglycine angiotensin II, respectively, at this temperature. At 22 degrees C, both tissues displayed rapid tachyphylaxis to [Asp1]angiotensin II which was reversed on prolonged incubation in peptide-free medium. At 37 degrees C, but at a lower than normal pH (pH 6.5 instead of 7.4), the rabbit aorta developed rapid tachyphylaxis to [Asp1)angiotensin II; this effect also was reversed on prolonged incubation in peptide-free medium. The rat uterus, at 30 degrees C, displayed tachyphylaxis to [Asp1]angiotensin II and analogs in order of rate of onset: [Sar1]angiotensin II greater than [Asp1]angiotensin II greater than [des-Asp1]angiotensin II. Over half of the individual uterine strips tested displayed no tachyphylaxis to [des-Asp1]angiotensin II. However, at 22 degrees C tachyphylaxis to all three compounds was rapid on onset and was reversed on prolonged incubation. The results indicate a correlation between affinity of the peptide analog for angiotensin receptor and its ability to induce tachyphylaxis. A possible involvement of membrane-bound enzymes in the onset and duration of tachyphylaxis is suggested.", "contents": "Further studies on angiotensin tachyphylaxis. Rabbit aorta and rat fundus do not display tachyphylaxis to angiotensin II (Asp1)angiotensin II) at 37 degrees C. These tissues do, however, display tachyphylaxis to [Sar1]angiotensin II (N-methylglycine 1 angiotensin II) and [dimethylglycine angiotensin II, respectively, at this temperature. At 22 degrees C, both tissues displayed rapid tachyphylaxis to [Asp1]angiotensin II which was reversed on prolonged incubation in peptide-free medium. At 37 degrees C, but at a lower than normal pH (pH 6.5 instead of 7.4), the rabbit aorta developed rapid tachyphylaxis to [Asp1)angiotensin II; this effect also was reversed on prolonged incubation in peptide-free medium. The rat uterus, at 30 degrees C, displayed tachyphylaxis to [Asp1]angiotensin II and analogs in order of rate of onset: [Sar1]angiotensin II greater than [Asp1]angiotensin II greater than [des-Asp1]angiotensin II. Over half of the individual uterine strips tested displayed no tachyphylaxis to [des-Asp1]angiotensin II. However, at 22 degrees C tachyphylaxis to all three compounds was rapid on onset and was reversed on prolonged incubation. The results indicate a correlation between affinity of the peptide analog for angiotensin receptor and its ability to induce tachyphylaxis. A possible involvement of membrane-bound enzymes in the onset and duration of tachyphylaxis is suggested."}
{"id": "PMID:6786", "title": "Studies on adrenal phenylethanolamine N- methyltransferase (PNMT) with S K & F 64139, a selective inhibitor.", "content": "SK&F 64139 is a potent, reversible inhibitor of phenylethanolamine N-methyltransferase; its IC50 concentration in our standard assay system was 1 X 10(-7) M. Kinetically, the compound is a competitive inhibitor with respect to norepinephrine but is uncompetitive when S-adenosylmethionine is the variable substrate. In contrast to a previously reported compound (SK&F 7698), the drug is only a weak alpha receptor antagonist (KB = 6 X 10(-6) M). In both the rat and squirrel monkey, SK&F 64139 produced dose-dependent decreases in the adrenal epinephrine content coupled with stoichiometrically equivalent increases in the norepinephrine pool(s). Further evidence for in vivo phenylethanolamine N-methyltransferase inhibitory activity was that the drug markedly inhibited the conversion of a tracer dose of 3H-norepinephrine to 3H-epinephrine in the rat adrenal gland after unit oral doses as low as 5 mg/kg.", "contents": "Studies on adrenal phenylethanolamine N- methyltransferase (PNMT) with S K & F 64139, a selective inhibitor. SK&F 64139 is a potent, reversible inhibitor of phenylethanolamine N-methyltransferase; its IC50 concentration in our standard assay system was 1 X 10(-7) M. Kinetically, the compound is a competitive inhibitor with respect to norepinephrine but is uncompetitive when S-adenosylmethionine is the variable substrate. In contrast to a previously reported compound (SK&F 7698), the drug is only a weak alpha receptor antagonist (KB = 6 X 10(-6) M). In both the rat and squirrel monkey, SK&F 64139 produced dose-dependent decreases in the adrenal epinephrine content coupled with stoichiometrically equivalent increases in the norepinephrine pool(s). Further evidence for in vivo phenylethanolamine N-methyltransferase inhibitory activity was that the drug markedly inhibited the conversion of a tracer dose of 3H-norepinephrine to 3H-epinephrine in the rat adrenal gland after unit oral doses as low as 5 mg/kg."}
{"id": "PMID:6787", "title": "The effects of metoclopramide in modifying the response of isolated guinea-pig ileum to various agonists.", "content": "Metoclopramide has a dual effect on intestinal smooth muscle. Low concentrations of metoclopramide cause potentiation of the responses to substance P, acetylcholine, histamine and barium chloride on the guinea-pig ileum. Higher concentrations produce a depression of smooth muscle responses which is characteristic of the tertiary amine local anesthetics. Neural pathways are involved in the mechanism of potentiation, since the enhancement of the responses to the agonists is abolished by tetrodotoxin. Atropine partially antagonizes the potentiating effect of metoclopramide implying that activation of muscarinic receptors is a contributing factor, but this does not fully explain the potentiation.", "contents": "The effects of metoclopramide in modifying the response of isolated guinea-pig ileum to various agonists. Metoclopramide has a dual effect on intestinal smooth muscle. Low concentrations of metoclopramide cause potentiation of the responses to substance P, acetylcholine, histamine and barium chloride on the guinea-pig ileum. Higher concentrations produce a depression of smooth muscle responses which is characteristic of the tertiary amine local anesthetics. Neural pathways are involved in the mechanism of potentiation, since the enhancement of the responses to the agonists is abolished by tetrodotoxin. Atropine partially antagonizes the potentiating effect of metoclopramide implying that activation of muscarinic receptors is a contributing factor, but this does not fully explain the potentiation."}
{"id": "PMID:6788", "title": "Statistical parameters of transmitter release at frog neuromuscular junctions treated with guanidine or tetraethylammonium.", "content": "Transmitter release at Mg++ -depressed frog neuromuscular junctions can be described using binomial statistics. The number of quanta (m) released by the nerve terminal action potential is directly proportional to the mean probability (p) that a quantum will be released and the number of quanta available for release (n). Guanidine or tetraethylammonium (TEA) increased m and n, but had no effect on p. At junctions depressed by d-tubocurarine, both compounds enhanced the amplitude of the initial end-plate potential, caused an accelerated rate of fade of end-plate potential amplitudes and raised the steady-state level of end-plate potential amplitude. This finding was interpreted to mean that guanidine and TEA increased transmitter mobilization and may be related to the increase by the compounds of the parameters n. If so, then the data support the idea that n represents the number of quanta available for release rather than the number of transmitter release sites in the terminal membrane. Neither compound affected the power relationship between [Ca++]o and transmitter release. When plotted on a double logarithmic basis, the slope of the line relating [Ca++]o to increased transmitter release was 3.7, a relationship not altered by the drugs. Thus, the compounds had no effect on the fundamental interaction between Ca++ and transmitter release sites. In contrast to [Ca++]o, the power relationship between increased transmitter release and the concentration of drug in the bathing solution was 0.69 for guanidine and 0.84 for TEA. Because of this finding, it was concluded that the compounds increased transmitter release by mechanisms other than or in addition to increasing Ca++ conductance.", "contents": "Statistical parameters of transmitter release at frog neuromuscular junctions treated with guanidine or tetraethylammonium. Transmitter release at Mg++ -depressed frog neuromuscular junctions can be described using binomial statistics. The number of quanta (m) released by the nerve terminal action potential is directly proportional to the mean probability (p) that a quantum will be released and the number of quanta available for release (n). Guanidine or tetraethylammonium (TEA) increased m and n, but had no effect on p. At junctions depressed by d-tubocurarine, both compounds enhanced the amplitude of the initial end-plate potential, caused an accelerated rate of fade of end-plate potential amplitudes and raised the steady-state level of end-plate potential amplitude. This finding was interpreted to mean that guanidine and TEA increased transmitter mobilization and may be related to the increase by the compounds of the parameters n. If so, then the data support the idea that n represents the number of quanta available for release rather than the number of transmitter release sites in the terminal membrane. Neither compound affected the power relationship between [Ca++]o and transmitter release. When plotted on a double logarithmic basis, the slope of the line relating [Ca++]o to increased transmitter release was 3.7, a relationship not altered by the drugs. Thus, the compounds had no effect on the fundamental interaction between Ca++ and transmitter release sites. In contrast to [Ca++]o, the power relationship between increased transmitter release and the concentration of drug in the bathing solution was 0.69 for guanidine and 0.84 for TEA. Because of this finding, it was concluded that the compounds increased transmitter release by mechanisms other than or in addition to increasing Ca++ conductance."}
{"id": "PMID:6789", "title": "Effect of fatty acids on the disposition of ammonia.", "content": "Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM octanoate, whereas glutamine synthetase was unaffected. Thus, the two main processes whereby ammonia is metabolized were inhibited by fatty acids at concentrations that exist pathologically, which accounts, at least in part, for the rise in blood ammonia in vivo.", "contents": "Effect of fatty acids on the disposition of ammonia. Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM octanoate, whereas glutamine synthetase was unaffected. Thus, the two main processes whereby ammonia is metabolized were inhibited by fatty acids at concentrations that exist pathologically, which accounts, at least in part, for the rise in blood ammonia in vivo."}
{"id": "PMID:6790", "title": "Microsomal reductive glycosidase.", "content": "Rat liver microsomes contain a phenobarbital inducible, NADPH dependent, reductive glycosidase capable of cleaving several anthracycline antibiotics, including adriamycin and daunorubicin, to deoxyaglycone products. The pH optimum for the reaction ranges from 7 to 7.4, and no metal requirements are noted. Molecular oxygen reversibly inhibits the microsomal enzyme greater than 95% at 20% oxygen partial pressure. Carbon monoxide, SKF 525A and sulfhydryl reagents are not inhibitory to the reaction, but the enzyme is sensitive to Cu++ and Zn++. Since the intact glycoside is necessary for conversion to the deoxyaglycone and a possible intermediate hydroxylated aglycone is not reduced to the deoxyaglycone, a concerted reaction mechanism is proposed. The reductive glycosidase activity is also present in rat brain, kidney and other tissues. Sensitivity of this enzyme to molecular oxygen suggests a possible regulatory role for the enzyme in vivo.", "contents": "Microsomal reductive glycosidase. Rat liver microsomes contain a phenobarbital inducible, NADPH dependent, reductive glycosidase capable of cleaving several anthracycline antibiotics, including adriamycin and daunorubicin, to deoxyaglycone products. The pH optimum for the reaction ranges from 7 to 7.4, and no metal requirements are noted. Molecular oxygen reversibly inhibits the microsomal enzyme greater than 95% at 20% oxygen partial pressure. Carbon monoxide, SKF 525A and sulfhydryl reagents are not inhibitory to the reaction, but the enzyme is sensitive to Cu++ and Zn++. Since the intact glycoside is necessary for conversion to the deoxyaglycone and a possible intermediate hydroxylated aglycone is not reduced to the deoxyaglycone, a concerted reaction mechanism is proposed. The reductive glycosidase activity is also present in rat brain, kidney and other tissues. Sensitivity of this enzyme to molecular oxygen suggests a possible regulatory role for the enzyme in vivo."}
{"id": "PMID:6791", "title": "Neutral protease activity and erythropoietin production in the rat after cobalt administration.", "content": "The generation of erythropoietin purportedly involves the interaction of an enzyme, of renal origin, and a circulating plasma protein substrate. Cobalt, which has the capacity to stimulate erythropoietin formation, was evaluated for its effects on renal and plasma protease activity; in addition, the nature of the erythrogenic mechanism was investigated. Rats receiving one s.c. injection of cobalt demonstrated significant increases in activity of renal cathepsins A and B. The activity of a plasma protease was also elevated in rats after cobalt treatment. Cathepsins A and B and plasma protease were sensitive to the same enzymatic inhibitory agents, and all three enzymes demonstrated activity patterns similar to that of the renal erythropoietic factor [enzyme(s) presumed responsible for generating erythropoietin] in rats treated with cobalt. These data may help to elucidate the mechanism of erythropoiesis.", "contents": "Neutral protease activity and erythropoietin production in the rat after cobalt administration. The generation of erythropoietin purportedly involves the interaction of an enzyme, of renal origin, and a circulating plasma protein substrate. Cobalt, which has the capacity to stimulate erythropoietin formation, was evaluated for its effects on renal and plasma protease activity; in addition, the nature of the erythrogenic mechanism was investigated. Rats receiving one s.c. injection of cobalt demonstrated significant increases in activity of renal cathepsins A and B. The activity of a plasma protease was also elevated in rats after cobalt treatment. Cathepsins A and B and plasma protease were sensitive to the same enzymatic inhibitory agents, and all three enzymes demonstrated activity patterns similar to that of the renal erythropoietic factor [enzyme(s) presumed responsible for generating erythropoietin] in rats treated with cobalt. These data may help to elucidate the mechanism of erythropoiesis."}
{"id": "PMID:6792", "title": "Cholestyramine-induced inhibition of salicylazosulfapyridine (sulfasalazine) metabolism by rat intestinal microflora.", "content": "The effect of multiple oral administration of the hypocholesterolemic agent cholestyramine (a strongly basic anion-exchange resin) on the metabolism of salicylazosulfapyridine by microflora present in the colon and cecum was assessed in conventional rats by following the time course of salicylazosulfapyridine and its metabolites in the urine and feces. The intestinal metabolism of salicylazosulfapyridine (a single 100 mg/kg oral dose), which involves reduction of the azo linkage by bacterial azo reductases and the liberation of sulfapyridine and 5-aminosalicylic acid (potential active metabolites of the drug), was markedly inhibited by the resin (250 mg/kg oral doses at -2, +2 and +6 hours), resulting in an enhanced fecal excretion of intact salicylazosulfapyridine. The existence of a rank-order correlation between the in vitro binding of salicylazosulfapyridine, sulfapyridine and 5-aminosalicylic acid to the resin and their fecal excretion pattern in resin-treated animals suggests that a direct cholestyramine-salicylazosulfapyridine interaction occurred within the intestinal tract and that in the bound state, the azo bond of the drug was inaccessible to bacterial azo reductases. These findings suggest that chronic oral administration of cholestyramine to patients with ulcerative colitis who are receiving salicylazosulfapyridine could result in a significant reduction in the absorption and metabolism of the drug and hence, in its therapeutic efficacy.", "contents": "Cholestyramine-induced inhibition of salicylazosulfapyridine (sulfasalazine) metabolism by rat intestinal microflora. The effect of multiple oral administration of the hypocholesterolemic agent cholestyramine (a strongly basic anion-exchange resin) on the metabolism of salicylazosulfapyridine by microflora present in the colon and cecum was assessed in conventional rats by following the time course of salicylazosulfapyridine and its metabolites in the urine and feces. The intestinal metabolism of salicylazosulfapyridine (a single 100 mg/kg oral dose), which involves reduction of the azo linkage by bacterial azo reductases and the liberation of sulfapyridine and 5-aminosalicylic acid (potential active metabolites of the drug), was markedly inhibited by the resin (250 mg/kg oral doses at -2, +2 and +6 hours), resulting in an enhanced fecal excretion of intact salicylazosulfapyridine. The existence of a rank-order correlation between the in vitro binding of salicylazosulfapyridine, sulfapyridine and 5-aminosalicylic acid to the resin and their fecal excretion pattern in resin-treated animals suggests that a direct cholestyramine-salicylazosulfapyridine interaction occurred within the intestinal tract and that in the bound state, the azo bond of the drug was inaccessible to bacterial azo reductases. These findings suggest that chronic oral administration of cholestyramine to patients with ulcerative colitis who are receiving salicylazosulfapyridine could result in a significant reduction in the absorption and metabolism of the drug and hence, in its therapeutic efficacy."}
{"id": "PMID:6793", "title": "The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines.", "content": "The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics.", "contents": "The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines. The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics."}
{"id": "PMID:6794", "title": "Evaluation of the discriminative effects of morphine in the rat.", "content": "The discriminative effects produced by morphine in the rat were evaluated using a two-choice, discrete trial avoidance task. Stimulus control of behavior was attained with a dose of morphine one-third to one-tenth of that used in previous studies. Morphine produced dose-related discriminative effects over a 100-fold dose range. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) oxymorphone, levorphanol, methadone and meperidine, narcotic analgesics from diverse chemical families, also produced dose-related morphine-like discriminative effects; 2) dextrorphan and thebaine, compounds structurally related to the narcotics but lacking narcotic activity, failed to produce morphine-like discriminative effects; 3) effects were blocked by the narcotic antagonist naloxone; and 4) tolerance to the discriminative effects developed upon the repeated administration of morphine and cross-tolerance extended to methadone. The discriminative effects produced by morphine were further characterized by evaluating the capacity of prototypes of other classes of psychoactive drugs to produce morphine-like discriminative effects. Profadol and pentazocine, euphorogenic analgesics with mixed agonist and narcotic antagonist properties, produced dose-related morphine-like discriminative effects whereas cyclazocine, a dysphorogenic analgesic with mixed agonist and narcotic-antagonist properties, did not. In addition, the nonopioid psychoactive drugs d-amphetamine, pentobarbital and chlorpromazine also failed to produce morphine-like discriminative effects. Thus, morphine-like discriminative effects were produced uniquely by the narcotic analgesics and euophorogenic analgesics with mixed agonist and narcotic antagonist properties. These results suggest that the component of action of morphine that enables it to function as a discriminative stimulus in the rat is analogous to the component of action of morphine responsible for producing subjective effects in man.", "contents": "Evaluation of the discriminative effects of morphine in the rat. The discriminative effects produced by morphine in the rat were evaluated using a two-choice, discrete trial avoidance task. Stimulus control of behavior was attained with a dose of morphine one-third to one-tenth of that used in previous studies. Morphine produced dose-related discriminative effects over a 100-fold dose range. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) oxymorphone, levorphanol, methadone and meperidine, narcotic analgesics from diverse chemical families, also produced dose-related morphine-like discriminative effects; 2) dextrorphan and thebaine, compounds structurally related to the narcotics but lacking narcotic activity, failed to produce morphine-like discriminative effects; 3) effects were blocked by the narcotic antagonist naloxone; and 4) tolerance to the discriminative effects developed upon the repeated administration of morphine and cross-tolerance extended to methadone. The discriminative effects produced by morphine were further characterized by evaluating the capacity of prototypes of other classes of psychoactive drugs to produce morphine-like discriminative effects. Profadol and pentazocine, euphorogenic analgesics with mixed agonist and narcotic antagonist properties, produced dose-related morphine-like discriminative effects whereas cyclazocine, a dysphorogenic analgesic with mixed agonist and narcotic-antagonist properties, did not. In addition, the nonopioid psychoactive drugs d-amphetamine, pentobarbital and chlorpromazine also failed to produce morphine-like discriminative effects. Thus, morphine-like discriminative effects were produced uniquely by the narcotic analgesics and euophorogenic analgesics with mixed agonist and narcotic antagonist properties. These results suggest that the component of action of morphine that enables it to function as a discriminative stimulus in the rat is analogous to the component of action of morphine responsible for producing subjective effects in man."}
{"id": "PMID:6795", "title": "Protein synthesis by a cell-free preparation from the bird malaria, Plasmodium lophurae.", "content": "Cytoplasmic polyribosomes were isolated from the avian malaria parasite Plasmodium lophurae by lysis with 0.15% Triton X-100 followed by high speed centrifugation through a discontinuous sucrose gradient. Polyribosomes were protected from nuclease degradation using 100 mug/ml heparin or 50 mug/ml dextran sulfate. Cell-free incorporation of radioisotope-labeled amino acids required a pH 5 fraction (duck reticulocyte), Mg2+, and an energy-generating system. The protein synthesizing system was stimulated by the addition of polyuridylic acid. Optimum conditions for protein synthesis by the plasmodial system are described. The effects of drugs on the cell-free protein synthesizing system using duck reticulocyte and plasmodial ribosomes are reported.", "contents": "Protein synthesis by a cell-free preparation from the bird malaria, Plasmodium lophurae. Cytoplasmic polyribosomes were isolated from the avian malaria parasite Plasmodium lophurae by lysis with 0.15% Triton X-100 followed by high speed centrifugation through a discontinuous sucrose gradient. Polyribosomes were protected from nuclease degradation using 100 mug/ml heparin or 50 mug/ml dextran sulfate. Cell-free incorporation of radioisotope-labeled amino acids required a pH 5 fraction (duck reticulocyte), Mg2+, and an energy-generating system. The protein synthesizing system was stimulated by the addition of polyuridylic acid. Optimum conditions for protein synthesis by the plasmodial system are described. The effects of drugs on the cell-free protein synthesizing system using duck reticulocyte and plasmodial ribosomes are reported."}
{"id": "PMID:6796", "title": "The serine hydroxymethyltransferase of Plasmodium lophurae.", "content": "Plasmodium lophurae serine hydroxymethyltransferase (EC 2.1.2.1) was partially purified and characterized by (NH4)2SO4 fractionation and chromatography on Sephadex G-100. The enzyme, precipitated by 3.0.3.3 M (NH4)2SO4, had a molecular weight of 68,300 as estimated by exclusion chromatography on G-100. The pH optimum of the enzyme was 6.8-7.6 in sodium phosphate-citrate buffer. Citrate stabilized the enzyme during storage in phosphate buffer at 4 C. The Km was 4.3 X 10(-3) M for L-serine and 2.5 X 10(-4) M for tetrahydrofolate.", "contents": "The serine hydroxymethyltransferase of Plasmodium lophurae. Plasmodium lophurae serine hydroxymethyltransferase (EC 2.1.2.1) was partially purified and characterized by (NH4)2SO4 fractionation and chromatography on Sephadex G-100. The enzyme, precipitated by 3.0.3.3 M (NH4)2SO4, had a molecular weight of 68,300 as estimated by exclusion chromatography on G-100. The pH optimum of the enzyme was 6.8-7.6 in sodium phosphate-citrate buffer. Citrate stabilized the enzyme during storage in phosphate buffer at 4 C. The Km was 4.3 X 10(-3) M for L-serine and 2.5 X 10(-4) M for tetrahydrofolate."}
{"id": "PMID:6797", "title": "Pentamidine transport and sensitivity in brucei-group trypanosomes.", "content": "Sensitivity to pentamidine of bloodstream forms and culture forms of Trypanosoma brucei brucei, strains of this subspecies, and strains of T. brucei rhodesiense characteristically differs in vitro. Analyses of transport parameters for pentamidine uptake in these organisms show differences that correspond with drug sensitivity. Long slender bloodstream forms of T. b. brucei have a high affinity for the drug and high rates of uptake at indicated by Km and Vmax values for [3H]pentamidine transport. Although pentamidine and stilbamidine resistance is associated with dyskinetoplasty, this condition does not itself confer resistance to pentamidine nor does it affect pentamidine transport. However, drug-resistant strains show lower rates for pentamidine transport as does T. b. rhodesiense, which is characteristically less sensitive to the drug. Of all the forms and strains studied, procyclic trypomastigotes were least sensitive to pentamidine and had a remarkable ability to exclude the drug.", "contents": "Pentamidine transport and sensitivity in brucei-group trypanosomes. Sensitivity to pentamidine of bloodstream forms and culture forms of Trypanosoma brucei brucei, strains of this subspecies, and strains of T. brucei rhodesiense characteristically differs in vitro. Analyses of transport parameters for pentamidine uptake in these organisms show differences that correspond with drug sensitivity. Long slender bloodstream forms of T. b. brucei have a high affinity for the drug and high rates of uptake at indicated by Km and Vmax values for [3H]pentamidine transport. Although pentamidine and stilbamidine resistance is associated with dyskinetoplasty, this condition does not itself confer resistance to pentamidine nor does it affect pentamidine transport. However, drug-resistant strains show lower rates for pentamidine transport as does T. b. rhodesiense, which is characteristically less sensitive to the drug. Of all the forms and strains studied, procyclic trypomastigotes were least sensitive to pentamidine and had a remarkable ability to exclude the drug."}
{"id": "PMID:6798", "title": "The influence of growth medium on the interactions between Bordetella pertussis and Staphylococcus aureus.", "content": "Previous observers showed that many strains of Staphylococcus aureus stimulated the growth of Bordetella pertussis but we have found the reverse: the growth of all available strains of B. pertussis on charcoal-agar medium was inhibited by a standard strain of S. aureus; and 17 of 18 strains of S. aureus (as well as several other organisms) inhibited the growth of a standard strain of B. pertussis. All inhibiting colonies had an unusual brown colouration on the charcoal agar used in the investigation. Both the brown colouration and the inhibitory property were caused by acid production, probably from the starch in the medium. We therefore suggest that media containing starch and blood should not be used in studies of bacterial interference.", "contents": "The influence of growth medium on the interactions between Bordetella pertussis and Staphylococcus aureus. Previous observers showed that many strains of Staphylococcus aureus stimulated the growth of Bordetella pertussis but we have found the reverse: the growth of all available strains of B. pertussis on charcoal-agar medium was inhibited by a standard strain of S. aureus; and 17 of 18 strains of S. aureus (as well as several other organisms) inhibited the growth of a standard strain of B. pertussis. All inhibiting colonies had an unusual brown colouration on the charcoal agar used in the investigation. Both the brown colouration and the inhibitory property were caused by acid production, probably from the starch in the medium. We therefore suggest that media containing starch and blood should not be used in studies of bacterial interference."}
{"id": "PMID:6799", "title": "Localization of calcium binding sites associated with the calcium spike in barnacle muscle.", "content": "La ion behaves as a competitive inhibitor of Ca ions on the calcium spike in the giant muscle fiber of the barnacle, Balanus nubilus. La-treated muscle fibers, in which the rate of rise of the spike was diminished to a known degree, have been examined with the electron-microscope. In such fibers dense particles are seen in association with the surface membrane and external lamina of the cell. La particles are not seen in association with fibers that have been allowed to recover from La inhibition before fixation. The number of La particles seen in association with the muscle fiber increases with increasing La concentration when the Ca and Mg concentrations are held constant and decreases with increasing Ca and Mg concentration when the La concentration is held constant. The results suggest that the La visible in the electron-microscope under the conditions of these experiments is bound to a class of sites similar to those involved in the Ca spike.", "contents": "Localization of calcium binding sites associated with the calcium spike in barnacle muscle. La ion behaves as a competitive inhibitor of Ca ions on the calcium spike in the giant muscle fiber of the barnacle, Balanus nubilus. La-treated muscle fibers, in which the rate of rise of the spike was diminished to a known degree, have been examined with the electron-microscope. In such fibers dense particles are seen in association with the surface membrane and external lamina of the cell. La particles are not seen in association with fibers that have been allowed to recover from La inhibition before fixation. The number of La particles seen in association with the muscle fiber increases with increasing La concentration when the Ca and Mg concentrations are held constant and decreases with increasing Ca and Mg concentration when the La concentration is held constant. The results suggest that the La visible in the electron-microscope under the conditions of these experiments is bound to a class of sites similar to those involved in the Ca spike."}
{"id": "PMID:6801", "title": "Characterization of Whitney's Clethrionomy gapperi virus isolates from Massachusetts.", "content": "Six strains of virus were recovered from the blood and/or liver of five Clethrionomys gapperi ochraceus trapped in southeastern Massachusetts during 1969. Biological, antigenic and physiochemical properties of these isolates are reported. USA M-2268a was selected as the reference strain. This strain was identical by complement-fixation and neutralization tests to Whitneys C. gapperie virus (USA 64-7855) from New York State and was related to, but distinct from, an unpublished agent (Johnson's Microtus montanus enterovirus USA M-1146) isolated in June, 1962 from voles trapped in Klamath County, Oregon. USA M-2268a was resistant to lipid solvents and acid pH and was stable at temperatures of 4 C, 22 C, and 37 C. Virus was detected over a 10-day observation period in four species of mosquitoes inoculated with USA M-2268a, although there was no evidence of infection or replication, and transmission attempts by bite failed. Neutralizing antibody was detected in C.g. gapperi and C. g. ochraceus in various habitats throughout the state.", "contents": "Characterization of Whitney's Clethrionomy gapperi virus isolates from Massachusetts. Six strains of virus were recovered from the blood and/or liver of five Clethrionomys gapperi ochraceus trapped in southeastern Massachusetts during 1969. Biological, antigenic and physiochemical properties of these isolates are reported. USA M-2268a was selected as the reference strain. This strain was identical by complement-fixation and neutralization tests to Whitneys C. gapperie virus (USA 64-7855) from New York State and was related to, but distinct from, an unpublished agent (Johnson's Microtus montanus enterovirus USA M-1146) isolated in June, 1962 from voles trapped in Klamath County, Oregon. USA M-2268a was resistant to lipid solvents and acid pH and was stable at temperatures of 4 C, 22 C, and 37 C. Virus was detected over a 10-day observation period in four species of mosquitoes inoculated with USA M-2268a, although there was no evidence of infection or replication, and transmission attempts by bite failed. Neutralizing antibody was detected in C.g. gapperi and C. g. ochraceus in various habitats throughout the state."}
{"id": "PMID:6802", "title": "Sea-blue histiocytes in a case of Takayasu arteritis.", "content": "Arteriographic, immunological, and bone marrow studies of a young woman with Takayasu arteritis disclosed the presence of sea-blue histiocytes in her bone marrow. We know of no other similar reports.", "contents": "Sea-blue histiocytes in a case of Takayasu arteritis. Arteriographic, immunological, and bone marrow studies of a young woman with Takayasu arteritis disclosed the presence of sea-blue histiocytes in her bone marrow. We know of no other similar reports."}
{"id": "PMID:6805", "title": "Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. I. In vitro effect.", "content": "Growth inhibitory effect of combined treatment of tetracycline (TC) and oleandomycin (OM), at a ratio of 2:1, on certain species of pathogenic bacteria including drug-resistant ones was examined. By the crossed paper strip method, synergistic effects were demonstrated against 9 of the 16 strains of Staphylococcus aureus, and all of the 5 strains of Escherichia coli studied. Antagonism was observed with none of the strains and with 2 strains of Streptococcus pyogenes and 2 strains of Streptococcus pneumoniae tested in the present experiments. The MICs determined by the agar dilution method, also gave similar results, although synergism was not conclusively demonstrated by this method. With representative strains of S. aureus, synergism was evidenced by quantitative measurement of growth inhibition. In some strains, 1.0 mug of one drug per ml of medium inhibited the induction of resistance to the second drug. Such a small dose of one drug also inhibited the development of a mutant resistant to the second drug. These inhibitory actions were thought to be one of the important factors causing the synergistic effect of TC and OM on drug resistant bacteria.", "contents": "Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. I. In vitro effect. Growth inhibitory effect of combined treatment of tetracycline (TC) and oleandomycin (OM), at a ratio of 2:1, on certain species of pathogenic bacteria including drug-resistant ones was examined. By the crossed paper strip method, synergistic effects were demonstrated against 9 of the 16 strains of Staphylococcus aureus, and all of the 5 strains of Escherichia coli studied. Antagonism was observed with none of the strains and with 2 strains of Streptococcus pyogenes and 2 strains of Streptococcus pneumoniae tested in the present experiments. The MICs determined by the agar dilution method, also gave similar results, although synergism was not conclusively demonstrated by this method. With representative strains of S. aureus, synergism was evidenced by quantitative measurement of growth inhibition. In some strains, 1.0 mug of one drug per ml of medium inhibited the induction of resistance to the second drug. Such a small dose of one drug also inhibited the development of a mutant resistant to the second drug. These inhibitory actions were thought to be one of the important factors causing the synergistic effect of TC and OM on drug resistant bacteria."}
{"id": "PMID:6806", "title": "Elevated plasma renin activity in aortitis syndrome.", "content": "Plasma renin activity (PRA) was measured in 38 cases of aortitis syndrome. The values of resting peripheral vein blood PRA were 32.2 +/- 4.2 (SE) mmug/ml. These values were 3 times higher than those of normal subjects. Hypertension due to renal arterial stenosis was observed in 18 cases. Their resting PRA values were 41.2 +/- 6.0 mmug/ml, while in the remaining 20 patients without renovascular hypertension those values were 24.2 +/- 5.4 mmug/ml. The patients belonging to aortic arch type or extensive type had 2 times higher PRA values than those of abdominal type. The patients with stenosis or obstruction of common carotid arteries had significantly higher PRA values than the patients without these lesions. Hyperresponse of renin secretion to upright posture was also observed in the same patients with carotid artery stenosis. Abnormal renin release in Takayasu's arteritis disappeared after denervation of the carotid sinus nerve. The present study suggests that the unstable state of carotid sinus reflex is the main cause for the hypersecretion of renin.", "contents": "Elevated plasma renin activity in aortitis syndrome. Plasma renin activity (PRA) was measured in 38 cases of aortitis syndrome. The values of resting peripheral vein blood PRA were 32.2 +/- 4.2 (SE) mmug/ml. These values were 3 times higher than those of normal subjects. Hypertension due to renal arterial stenosis was observed in 18 cases. Their resting PRA values were 41.2 +/- 6.0 mmug/ml, while in the remaining 20 patients without renovascular hypertension those values were 24.2 +/- 5.4 mmug/ml. The patients belonging to aortic arch type or extensive type had 2 times higher PRA values than those of abdominal type. The patients with stenosis or obstruction of common carotid arteries had significantly higher PRA values than the patients without these lesions. Hyperresponse of renin secretion to upright posture was also observed in the same patients with carotid artery stenosis. Abnormal renin release in Takayasu's arteritis disappeared after denervation of the carotid sinus nerve. The present study suggests that the unstable state of carotid sinus reflex is the main cause for the hypersecretion of renin."}
{"id": "PMID:6807", "title": "Perinephritis hypertension in monkeys. I. An increase of plasma renin activity associated with increased permeability of retinal vessels and angionecrosis.", "content": "The renal parenchyma of 5 crub-eating monkeys (Macaca irus) was wrapped by cellophane, and plasma renin activity, blood pressure and vascular permeability of ocular ground were measured in comparison with 5 unoperated control monkeys. The results demonstrated that increases of systolic arterial pressure, plasma renin activity, and permeability of the retinal vessels were found in 4 operated monkeys. There was no such abnormal finding in the unoperated control monkeys. Generally there was a rough parallelism among levels of plasma renin activity and systolic blood pressure, an increase of permeability of retinal vessels and fibrinoid angionecrosis and/or necrotizing angitis similar to polyarteritis nodosa.", "contents": "Perinephritis hypertension in monkeys. I. An increase of plasma renin activity associated with increased permeability of retinal vessels and angionecrosis. The renal parenchyma of 5 crub-eating monkeys (Macaca irus) was wrapped by cellophane, and plasma renin activity, blood pressure and vascular permeability of ocular ground were measured in comparison with 5 unoperated control monkeys. The results demonstrated that increases of systolic arterial pressure, plasma renin activity, and permeability of the retinal vessels were found in 4 operated monkeys. There was no such abnormal finding in the unoperated control monkeys. Generally there was a rough parallelism among levels of plasma renin activity and systolic blood pressure, an increase of permeability of retinal vessels and fibrinoid angionecrosis and/or necrotizing angitis similar to polyarteritis nodosa."}
{"id": "PMID:6808", "title": "Hemodynamics of experimentally hypertensive rats in conscious and anesthetized states.", "content": "Cardiac output was measured by a pulse contour method in reno-vascular hypertensive rats, deoxycorticosterone (DOC) hypertensive rats and normotensive control Wistar rats in the conscious state. All rats were male in sex and 12-13 weeks of age (2-3 weeks after operation in the hypertensive rats). Cardiac output per body weight was not significantly different among the groups. Therefore, the hypertension in the experimentally hypertensive rats in the conscious state was ascribable to an increased total peripheral resistance. After anesthesia with pentobarbital and thoracotomy, the DOC rats were no longer hypertensive. However, in the renovascular hypertensive rats, the hypertensive state due to an increase in vascular resistance persisted after anesthesia, thoracotomy, and even ganglion blockade with hexamethonium bromide, indicating the importance of non-neural factors in the renovascular hypertension. Aortic compliance measured in vivo under anesthesia was smaller in either the renovascular or DOC hypertensive rats than in the control rats before and after ganglion blockade, which suggests a non-neural hardening of elastic vessels in the experimental hypertensions.", "contents": "Hemodynamics of experimentally hypertensive rats in conscious and anesthetized states. Cardiac output was measured by a pulse contour method in reno-vascular hypertensive rats, deoxycorticosterone (DOC) hypertensive rats and normotensive control Wistar rats in the conscious state. All rats were male in sex and 12-13 weeks of age (2-3 weeks after operation in the hypertensive rats). Cardiac output per body weight was not significantly different among the groups. Therefore, the hypertension in the experimentally hypertensive rats in the conscious state was ascribable to an increased total peripheral resistance. After anesthesia with pentobarbital and thoracotomy, the DOC rats were no longer hypertensive. However, in the renovascular hypertensive rats, the hypertensive state due to an increase in vascular resistance persisted after anesthesia, thoracotomy, and even ganglion blockade with hexamethonium bromide, indicating the importance of non-neural factors in the renovascular hypertension. Aortic compliance measured in vivo under anesthesia was smaller in either the renovascular or DOC hypertensive rats than in the control rats before and after ganglion blockade, which suggests a non-neural hardening of elastic vessels in the experimental hypertensions."}
{"id": "PMID:6813", "title": "Enhancement of sulphatide metabolism in the hypertrophied kidney of C3H/He mouse with reference to [Na+, K+]-dependent ATPase.", "content": "Sulphatide (cerebroside sulphate) metabolism of C3H/He mouse kidney was investigated in the course of compensatory renal hypertrophy in association with the change of [Na+,K+]-dependent ATPase, arylsulfatase A and beta-galactosidase activity. A remarkable increase in 35S incorporation into kidney sulphatide was observed 24 hours and especially 7 days after unilateral nephrectomy. In contrast, no significant alteration of 32P incorporation into major phospholipids such as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin was demonstrated in the compensatory hypertrophied mouse kidney. [Na+, K+]-dependent ATPase increased to 126% of control in the remaining kidneys on 7 days after operation. Specific increase in 35S specific activity of kidney sulphatide suggests its possible link with the process of active ion transport through membrane-bound [Na+,K+]-dependent ATPase. Arylsulphatase A activity increased to 151% of control on  days, while little change was observed in beta-galactosidase activity. These results suggest a sole concern of a turnover of sulphate moiety of sulphatide molecule in the elevated metabolism.", "contents": "Enhancement of sulphatide metabolism in the hypertrophied kidney of C3H/He mouse with reference to [Na+, K+]-dependent ATPase. Sulphatide (cerebroside sulphate) metabolism of C3H/He mouse kidney was investigated in the course of compensatory renal hypertrophy in association with the change of [Na+,K+]-dependent ATPase, arylsulfatase A and beta-galactosidase activity. A remarkable increase in 35S incorporation into kidney sulphatide was observed 24 hours and especially 7 days after unilateral nephrectomy. In contrast, no significant alteration of 32P incorporation into major phospholipids such as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin was demonstrated in the compensatory hypertrophied mouse kidney. [Na+, K+]-dependent ATPase increased to 126% of control in the remaining kidneys on 7 days after operation. Specific increase in 35S specific activity of kidney sulphatide suggests its possible link with the process of active ion transport through membrane-bound [Na+,K+]-dependent ATPase. Arylsulphatase A activity increased to 151% of control on  days, while little change was observed in beta-galactosidase activity. These results suggest a sole concern of a turnover of sulphate moiety of sulphatide molecule in the elevated metabolism."}
{"id": "PMID:6814", "title": "Effect of taurine on alteration in adrenal functions induced by stress.", "content": "When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine. In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preventive effects on the decline in adrenal catecholamines. The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on  the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of adrenaline in the adrenal gland measured by the rate of decline of this amine following alpha-methyl-tyrosine administration. The administration of taurine, in both in vivo and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-beta-hydroxylase was not significantly affected. The stress-induced elevation of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mechanism most likly involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules.", "contents": "Effect of taurine on alteration in adrenal functions induced by stress. When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine. In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preventive effects on the decline in adrenal catecholamines. The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on  the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of adrenaline in the adrenal gland measured by the rate of decline of this amine following alpha-methyl-tyrosine administration. The administration of taurine, in both in vivo and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-beta-hydroxylase was not significantly affected. The stress-induced elevation of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mechanism most likly involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules."}
{"id": "PMID:6815", "title": "A clinical comparison of syrup of ipecac and apomorphine use in adults.", "content": "A prospective, randomized study was performed to compare syrup of ipecac to apomorphine as the emetic of choice in poisoning cases. Of the 28 adults studied, 15 patients (54%) received 30 ml of ipecac orally and 13 received 0.1 mg/kg apomorphine subcutaneously. Emesis was successfully induced with initial therapy in 13 of 15 (87%) ipecac-treated patients and 10 of 13 (77%) apomorphine-treated patients. In the ipecac group the mean latency period before onset of vomiting was 11.6 minutes (range 4 to 26 min) and in the apomorphine group, 5.3 minutes (range 2 to 13 min) (P less than .01). In the ipecac group, one patient suffered moderate central nervous system (CNS) depression. No hypotension or respiratory depression was observed in this group. In the apomorphine group significant CNS depression developed in eight patients (62%), hypotension developed in five (38%) and respiratory depression in one. There was no consistent relationship between type of poison ingested and occurrence of side effects.", "contents": "A clinical comparison of syrup of ipecac and apomorphine use in adults. A prospective, randomized study was performed to compare syrup of ipecac to apomorphine as the emetic of choice in poisoning cases. Of the 28 adults studied, 15 patients (54%) received 30 ml of ipecac orally and 13 received 0.1 mg/kg apomorphine subcutaneously. Emesis was successfully induced with initial therapy in 13 of 15 (87%) ipecac-treated patients and 10 of 13 (77%) apomorphine-treated patients. In the ipecac group the mean latency period before onset of vomiting was 11.6 minutes (range 4 to 26 min) and in the apomorphine group, 5.3 minutes (range 2 to 13 min) (P less than .01). In the ipecac group, one patient suffered moderate central nervous system (CNS) depression. No hypotension or respiratory depression was observed in this group. In the apomorphine group significant CNS depression developed in eight patients (62%), hypotension developed in five (38%) and respiratory depression in one. There was no consistent relationship between type of poison ingested and occurrence of side effects."}
{"id": "PMID:6816", "title": "Monitoring resuscitation of primates from hemorrhagic and septic shock.", "content": "Monitoring data in 16 primates subjected to septic or hemorrhagic shock and resuscitated with various solutions is presented. From a paractical standpoint, central venous pressure and urine output appear to be the best indices to use in the emergency department for resuscitation of the shock victim. The sophisticated measurements such as cardiac output, thermodye volumes, pulmonary artery wedge pressure and oxygen consumption should be reserved for the individual with depressed cardiovascular reserves and who needs \"fine tuning\" of his volume status.", "contents": "Monitoring resuscitation of primates from hemorrhagic and septic shock. Monitoring data in 16 primates subjected to septic or hemorrhagic shock and resuscitated with various solutions is presented. From a paractical standpoint, central venous pressure and urine output appear to be the best indices to use in the emergency department for resuscitation of the shock victim. The sophisticated measurements such as cardiac output, thermodye volumes, pulmonary artery wedge pressure and oxygen consumption should be reserved for the individual with depressed cardiovascular reserves and who needs \"fine tuning\" of his volume status."}
{"id": "PMID:6819", "title": "[Fertility after treatment with HCG for undescended testes (author's tranls)].", "content": "151 out of 212 adolescents having had been treated by human chorionic gonadotrophin (HCG) before puberty because of undescended testes, were re-examined 7 to 12 years later at an individual age of at least 17 years. In 121 of them a semen specimen for sperm counts could be obtained. In 10 patients, however, no ejaculate could be collected because of their hypogonadism. 78 of these 121 patients examined by sperm count had a sufficient testicular descensus after HCG treatment. In 43 adolescents HCG therapy failed, therefore subsequent orchidopexy was performed. A normal sperm count was seen in only 39 per cent of the 121 patients. After unilateral testicular maldescensus 18%, after bilateral maldescensus 43% of the patients had to be evaluated as prospectively infertile. Maier and Spann reported sperm counts below 10(6)/ml in 9 out of 17 patients with bilateral maldescensus who had been treated by surgery alone. In the present study, however, only 9 out of 35 individuals treated for bilateral maldescensus by HCG alone showed sperm counts below 10(6)/ml. Plasma LH and FSH concentrations were determined in 93 patients, 6 out of which showed hypergonadotrophic values of FSH and sperm counts below 10(7)/ml. Subsequently, 3 cases of Klinefelter's syndrome could be diagnosed among the total group of 121 patients. The etiology of testicular maldescensus is by no means uniform since anatomical, endocrine and/or chromosomal factors are involved.", "contents": "[Fertility after treatment with HCG for undescended testes (author's tranls)]. 151 out of 212 adolescents having had been treated by human chorionic gonadotrophin (HCG) before puberty because of undescended testes, were re-examined 7 to 12 years later at an individual age of at least 17 years. In 121 of them a semen specimen for sperm counts could be obtained. In 10 patients, however, no ejaculate could be collected because of their hypogonadism. 78 of these 121 patients examined by sperm count had a sufficient testicular descensus after HCG treatment. In 43 adolescents HCG therapy failed, therefore subsequent orchidopexy was performed. A normal sperm count was seen in only 39 per cent of the 121 patients. After unilateral testicular maldescensus 18%, after bilateral maldescensus 43% of the patients had to be evaluated as prospectively infertile. Maier and Spann reported sperm counts below 10(6)/ml in 9 out of 17 patients with bilateral maldescensus who had been treated by surgery alone. In the present study, however, only 9 out of 35 individuals treated for bilateral maldescensus by HCG alone showed sperm counts below 10(6)/ml. Plasma LH and FSH concentrations were determined in 93 patients, 6 out of which showed hypergonadotrophic values of FSH and sperm counts below 10(7)/ml. Subsequently, 3 cases of Klinefelter's syndrome could be diagnosed among the total group of 121 patients. The etiology of testicular maldescensus is by no means uniform since anatomical, endocrine and/or chromosomal factors are involved."}
{"id": "PMID:6820", "title": "[Carbromal intoxication: influence of hemodialysis and hemoperfusion].", "content": "It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients.", "contents": "[Carbromal intoxication: influence of hemodialysis and hemoperfusion]. It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients."}
{"id": "PMID:6826", "title": "Monitoring of midmyocardial and subendocardial pH in normal and ischemic ventricles.", "content": "Midmyocardial and subendocardial pH monitoring was used as an indirect method for continuous evaluation of regional canine myocardial ischemia. Left ventricular midmyocardial pH (pHm) at 4 mm. depth was monitored in 10 dogs, under resting conditions, by means of a 5 mm. Beckman pH probe. pHm was 6.96 +/- 0.03, recorded at myocardial temperatures of 35 to 37 degrees C. Ischemia was then produced by snare occlusion of the proximal left main coronary artery for 2 minutes. pHm decreased to 6.87 +/- 0.03 (p less than 0.01) at 1 minute and 6.80 +/- 0.04 (p less than 0.005) in 2 minutes. When flow was restored, pHm returned toward normal within 2 minutes (pH 6.86 +/- 0.03) and at 5 minutes had returned to control values (pH 6.93 +/- 0.03). In another 5 dogs under similar conditions, pHm at 4 mm. and subendocardial pH (pHe at 8 mm.) were measured. Baseline pHm (6.97 +/- 0.01) and pHe (6.84 +/- 0.02) levels were significantly different (p less than 0.0005). After 2 minutes of ischemia, pHm was 6.82 +/- 0.03, whereas pHe decreased to 6.78 +/- 0.04 (p less than 0.1). Five minutes after snare release, pHe remained at 6.73 +/- 0.07; pHm (6.93 +/- 0.03) returned to control values. Both pHm (6.93 +/- 0.02) and pHe (6.84 +/- 0.09) levels were normal 15 minutes after release of the snare. The midmyocardium and subendocardium have different pH levels which can be monitored. Ischemia produces different pH patterns in these layers. pHm returns to control values within 5 minutes after 2 minutes of ischemia, whereas pHe remains depressed for at least 5 minutes. pH monitoring provides an accurate and simple method for on-line evaluation of endocardial ischemia.", "contents": "Monitoring of midmyocardial and subendocardial pH in normal and ischemic ventricles. Midmyocardial and subendocardial pH monitoring was used as an indirect method for continuous evaluation of regional canine myocardial ischemia. Left ventricular midmyocardial pH (pHm) at 4 mm. depth was monitored in 10 dogs, under resting conditions, by means of a 5 mm. Beckman pH probe. pHm was 6.96 +/- 0.03, recorded at myocardial temperatures of 35 to 37 degrees C. Ischemia was then produced by snare occlusion of the proximal left main coronary artery for 2 minutes. pHm decreased to 6.87 +/- 0.03 (p less than 0.01) at 1 minute and 6.80 +/- 0.04 (p less than 0.005) in 2 minutes. When flow was restored, pHm returned toward normal within 2 minutes (pH 6.86 +/- 0.03) and at 5 minutes had returned to control values (pH 6.93 +/- 0.03). In another 5 dogs under similar conditions, pHm at 4 mm. and subendocardial pH (pHe at 8 mm.) were measured. Baseline pHm (6.97 +/- 0.01) and pHe (6.84 +/- 0.02) levels were significantly different (p less than 0.0005). After 2 minutes of ischemia, pHm was 6.82 +/- 0.03, whereas pHe decreased to 6.78 +/- 0.04 (p less than 0.1). Five minutes after snare release, pHe remained at 6.73 +/- 0.07; pHm (6.93 +/- 0.03) returned to control values. Both pHm (6.93 +/- 0.02) and pHe (6.84 +/- 0.09) levels were normal 15 minutes after release of the snare. The midmyocardium and subendocardium have different pH levels which can be monitored. Ischemia produces different pH patterns in these layers. pHm returns to control values within 5 minutes after 2 minutes of ischemia, whereas pHe remains depressed for at least 5 minutes. pH monitoring provides an accurate and simple method for on-line evaluation of endocardial ischemia."}
{"id": "PMID:6827", "title": "[The use of \"mesh graft\" in traumatology].", "content": "Vandeput and J. Tanner's method for the reconstruction of the reticular grafting skin has been used and is recommended by the authors for the treatment of not only the thermic--, but of the mechanis lesions. The author has obtained very good results. The method is discussed and its advantages are pointed out.", "contents": "[The use of \"mesh graft\" in traumatology]. Vandeput and J. Tanner's method for the reconstruction of the reticular grafting skin has been used and is recommended by the authors for the treatment of not only the thermic--, but of the mechanis lesions. The author has obtained very good results. The method is discussed and its advantages are pointed out."}
{"id": "PMID:6828", "title": "[Solitary tuberculoma in the tendonous section of the m. quadriceps].", "content": "A case of isolated tuberculosis observed in the tensinous part of the quadriceps muscle is reported by the authors. The rarity of the case is pointed out. A few possibilities of the development of this tuberculoma are dealt with. In the authors' case the focus developed probably after haematogenous generalization. One year after the operation the patient is symptomfree and has no complaints.", "contents": "[Solitary tuberculoma in the tendonous section of the m. quadriceps]. A case of isolated tuberculosis observed in the tensinous part of the quadriceps muscle is reported by the authors. The rarity of the case is pointed out. A few possibilities of the development of this tuberculoma are dealt with. In the authors' case the focus developed probably after haematogenous generalization. One year after the operation the patient is symptomfree and has no complaints."}
{"id": "PMID:6829", "title": "[The effect of chitin powder on the healing of skin wounds].", "content": "Locally administered chitin powder has influences favourably the healing of the circular, open skin wounds on the dorsum. The tensil strength of the 7 days' incised skin wounds on the dorsum has increased under the effect of chitin powder suspension administered 3 days before the incision. The total hydroxyproline content was not influenced significantly by the chitin powder either in the case of circular open skin wounds or of incised dorsal skin wounds.", "contents": "[The effect of chitin powder on the healing of skin wounds]. Locally administered chitin powder has influences favourably the healing of the circular, open skin wounds on the dorsum. The tensil strength of the 7 days' incised skin wounds on the dorsum has increased under the effect of chitin powder suspension administered 3 days before the incision. The total hydroxyproline content was not influenced significantly by the chitin powder either in the case of circular open skin wounds or of incised dorsal skin wounds."}
{"id": "PMID:6830", "title": "[Constitution and structure of human tendons].", "content": "In this introductory study our actual knowledge on the tendons is resumed and it is pointed out that on the basis of this knowledge no explanation is given as regards the pathomechanism of the \"spontaneous\" tendon ruptures. The authors' concept on the tendons as motor units is discussed. The examinations are dealt with, by which the authors intend to revise the conventional static tendon model.", "contents": "[Constitution and structure of human tendons]. In this introductory study our actual knowledge on the tendons is resumed and it is pointed out that on the basis of this knowledge no explanation is given as regards the pathomechanism of the \"spontaneous\" tendon ruptures. The authors' concept on the tendons as motor units is discussed. The examinations are dealt with, by which the authors intend to revise the conventional static tendon model."}
{"id": "PMID:6831", "title": "[Incidence of blood aspiration in fatal fractures of the base of the skull].", "content": "The frequency of blood inhalation has been examined by the authors in the 15 years' material of the Institute of Forensic Medicine of the \"Semmelweis\" University Medical School. Out of 51.308 post mortem examinations 487 cases of isolated basicranial fractures were found. Out of them in 265 cases (=54%) blood inhalation as cause of death was verified. Attention is called to the importance of prompt blood aspiration in patients with basicranial fracture.", "contents": "[Incidence of blood aspiration in fatal fractures of the base of the skull]. The frequency of blood inhalation has been examined by the authors in the 15 years' material of the Institute of Forensic Medicine of the \"Semmelweis\" University Medical School. Out of 51.308 post mortem examinations 487 cases of isolated basicranial fractures were found. Out of them in 265 cases (=54%) blood inhalation as cause of death was verified. Attention is called to the importance of prompt blood aspiration in patients with basicranial fracture."}
{"id": "PMID:6832", "title": "[Open fractures of the hand joints].", "content": "In the authors' opinion the optimal treatment of the open fractures of the hand articulations is the internal fixation offering the best fixation possible--this being the best antidote of the inflammatory complications and assuring the satisfactory late functional results. The splinting (stabliizing) methods known so far--as well as the preventive measures applied by the authors against inflammatory complications are discussed.", "contents": "[Open fractures of the hand joints]. In the authors' opinion the optimal treatment of the open fractures of the hand articulations is the internal fixation offering the best fixation possible--this being the best antidote of the inflammatory complications and assuring the satisfactory late functional results. The splinting (stabliizing) methods known so far--as well as the preventive measures applied by the authors against inflammatory complications are discussed."}
{"id": "PMID:6833", "title": "[Superficial tendoplasty after injury of the intrinsic muscle].", "content": "In 6 fingers of two injured patients, after the lesion of the intrinsic musculature of the finger with three phalanges Bunnell's sublime tendoplasty has been performed by the authors. Satisfactory functional results have been obtained, therefore the method is recommended by the authors for the treatment of similar lesions.", "contents": "[Superficial tendoplasty after injury of the intrinsic muscle]. In 6 fingers of two injured patients, after the lesion of the intrinsic musculature of the finger with three phalanges Bunnell's sublime tendoplasty has been performed by the authors. Satisfactory functional results have been obtained, therefore the method is recommended by the authors for the treatment of similar lesions."}
{"id": "PMID:6834", "title": "[Experimental tendon sheath formation by free transplantation of a long vein segment (comparative study of adhesions formed around free grafts and pedicled grafts)].", "content": "In dog experiments, in order to improve the functions after tendinous injuries diphasic operations have been performed by the authors. In the first phase, after the extirpation of the tendon of the 2nd finger its area has been bridged over by a 5-6 cm long autologous vein transplant, cannulated with a silicone rubber bar. After 4 weeks, after the vascularization of the vein transplant the silicone bar has been removed from a new approach, and through the \"tunnel\" formed in this way and padded with silicone a tendon has been pulled through with two different methods: 1. according to the method of Paneva-Holevitch a diphasic pedicled tendon transplant and 2. a free tendon transplant. No differences were found as regards the adhesions, the vascularization and the tissular structure of the tendon. It may be presumed that also the distal portion of the pedicled tendon transplant is really a free tendon transplant.", "contents": "[Experimental tendon sheath formation by free transplantation of a long vein segment (comparative study of adhesions formed around free grafts and pedicled grafts)]. In dog experiments, in order to improve the functions after tendinous injuries diphasic operations have been performed by the authors. In the first phase, after the extirpation of the tendon of the 2nd finger its area has been bridged over by a 5-6 cm long autologous vein transplant, cannulated with a silicone rubber bar. After 4 weeks, after the vascularization of the vein transplant the silicone bar has been removed from a new approach, and through the \"tunnel\" formed in this way and padded with silicone a tendon has been pulled through with two different methods: 1. according to the method of Paneva-Holevitch a diphasic pedicled tendon transplant and 2. a free tendon transplant. No differences were found as regards the adhesions, the vascularization and the tissular structure of the tendon. It may be presumed that also the distal portion of the pedicled tendon transplant is really a free tendon transplant."}
{"id": "PMID:6835", "title": "[Pig skin xenograft in burns. I. Technology, laboratory studies. II. Clinical experience].", "content": "The technology of the preparation of certainly sterile xenograft--pig's skin has been examined by the authors before the therapeutical use. On the basis of their examinations it was found by the authors that 2500 krad gamma radiation is suitable for the sterilization of the pig's skin--for the preparation of both the nature or lyophilized skin--since at this radiation value the pig's skin suffers no injury. After the preparation of the xenograft its clinical use has been initiated with certainly sterile material in children with burns. Xenograft has been used on 50 occasions, chiefly after surgical necrectomy, as provisional biological dressing. On the basis of their satisfactors results the authors advocate the use of the xenograft in burns, in certain skin affections, in clinical pictures concomitant with skinning and cutaneous necrosis and generally in all cases, in which skin grafting in necessary.", "contents": "[Pig skin xenograft in burns. I. Technology, laboratory studies. II. Clinical experience]. The technology of the preparation of certainly sterile xenograft--pig's skin has been examined by the authors before the therapeutical use. On the basis of their examinations it was found by the authors that 2500 krad gamma radiation is suitable for the sterilization of the pig's skin--for the preparation of both the nature or lyophilized skin--since at this radiation value the pig's skin suffers no injury. After the preparation of the xenograft its clinical use has been initiated with certainly sterile material in children with burns. Xenograft has been used on 50 occasions, chiefly after surgical necrectomy, as provisional biological dressing. On the basis of their satisfactors results the authors advocate the use of the xenograft in burns, in certain skin affections, in clinical pictures concomitant with skinning and cutaneous necrosis and generally in all cases, in which skin grafting in necessary."}
{"id": "PMID:6836", "title": "[Radioisotopes used in the diagnosis of bone diseases].", "content": "The radiopharmacons produced in Hungary and suitable for the demonstration of reactive bone alterations are discussed by the authors. These pharmacons are the following: 85ScCl2=Strontiumchloride, 153Sm-EDTA=Samarium ethylendiamintetraacetate, 169Yb-citrate=Ytterbium-citrate, 99mTc-HEDSPA=Technetium-hydroxy-ethylene-diphosphonate, 99mTc-pyrophosphate. The scintigraphic pictures obtained by the use of these radiopharmacons are presented. On the basis of their experimental examinations the numerous advantages of the use of 99mTc-HEDSPA are pointed out and the possibilities are outlines, which are to be obtained in the detection of occult bone alterations, in the examination of juvenile patients and perhaps in the case of osteotransplantation.", "contents": "[Radioisotopes used in the diagnosis of bone diseases]. The radiopharmacons produced in Hungary and suitable for the demonstration of reactive bone alterations are discussed by the authors. These pharmacons are the following: 85ScCl2=Strontiumchloride, 153Sm-EDTA=Samarium ethylendiamintetraacetate, 169Yb-citrate=Ytterbium-citrate, 99mTc-HEDSPA=Technetium-hydroxy-ethylene-diphosphonate, 99mTc-pyrophosphate. The scintigraphic pictures obtained by the use of these radiopharmacons are presented. On the basis of their experimental examinations the numerous advantages of the use of 99mTc-HEDSPA are pointed out and the possibilities are outlines, which are to be obtained in the detection of occult bone alterations, in the examination of juvenile patients and perhaps in the case of osteotransplantation."}
{"id": "PMID:6838", "title": "[Surgical treatment of knee joint ligaments].", "content": "Because injuries of the ligaments of the knee joint, during 11 years 58 operations have been performed by the authors. In order to evaluate the late results, all patients have been reexamined 1 to 10 years after the operation. In more than the half of the cases at the least 2 ligament injuries have been operated on. 31 patients underwent the operation within two weeks after the injury, and the other patients later on. The authors' material and results are compared also with the data of the literature. In the authors' opinion the result of the surgical treatment is not decisively depending on the chosen operative method. The early and exact diagnosis--forming the basis of the suitable treatment--are of far greater importance. The perfect operative technique and the consequent rehabilitation are indispensable requirements of all surgical interventions. After severe ligament injury of the knee joint the surgical intervention allowed to 2/3 or 3/4 of the injured patients to return to work with stabilized knee. In younger patients also sporting may be possible. Therefore the surgical treatment of the knees, which became unstable because of ligament injury, is absolutely indicated in patients in working age.", "contents": "[Surgical treatment of knee joint ligaments]. Because injuries of the ligaments of the knee joint, during 11 years 58 operations have been performed by the authors. In order to evaluate the late results, all patients have been reexamined 1 to 10 years after the operation. In more than the half of the cases at the least 2 ligament injuries have been operated on. 31 patients underwent the operation within two weeks after the injury, and the other patients later on. The authors' material and results are compared also with the data of the literature. In the authors' opinion the result of the surgical treatment is not decisively depending on the chosen operative method. The early and exact diagnosis--forming the basis of the suitable treatment--are of far greater importance. The perfect operative technique and the consequent rehabilitation are indispensable requirements of all surgical interventions. After severe ligament injury of the knee joint the surgical intervention allowed to 2/3 or 3/4 of the injured patients to return to work with stabilized knee. In younger patients also sporting may be possible. Therefore the surgical treatment of the knees, which became unstable because of ligament injury, is absolutely indicated in patients in working age."}
{"id": "PMID:6839", "title": "[The so-called \"intact\" side in Perthes' disease].", "content": "Out of the 32 patients treated with Perthes' disease in the Orthopaedic Department of the University Medical School, PECS, in 9 cases bilateral course has been observed. Out of 23 children with Perthes' disease and unilateral, typical course the authors have observed in 12 patients pathological X-ray signs on the \"intact\" side--which were more distinct on the epiphyseal center, but chiefly on the growth intervertebral disk and on the metaphysis. In the same time, no subjective complaints and no other objective clinical symptoms pointed to Perthes' disease. It is supposed by the authors that transient ischaemic state may occur also on the side classified as \"intact\", but with reversible consequences, thus, the alterations of the epiphyseal center do not display the typical course of the Perthes' disease.", "contents": "[The so-called \"intact\" side in Perthes' disease]. Out of the 32 patients treated with Perthes' disease in the Orthopaedic Department of the University Medical School, PECS, in 9 cases bilateral course has been observed. Out of 23 children with Perthes' disease and unilateral, typical course the authors have observed in 12 patients pathological X-ray signs on the \"intact\" side--which were more distinct on the epiphyseal center, but chiefly on the growth intervertebral disk and on the metaphysis. In the same time, no subjective complaints and no other objective clinical symptoms pointed to Perthes' disease. It is supposed by the authors that transient ischaemic state may occur also on the side classified as \"intact\", but with reversible consequences, thus, the alterations of the epiphyseal center do not display the typical course of the Perthes' disease."}
{"id": "PMID:6840", "title": "[Alloplastic reconstruction of the proximal third of the femur. Case report].", "content": "The case of a woman, aged 51, is reported. In this patient, in 1961, because of an alteration developed in the right neck of the femur--and trochanter area--diagnosed for osteoclastoma--irradiation treatment has been performed. After steadily increasing complaints the patient suffered in 1965 a pathological fracture. In 1966 after resection of the proximal third of the femurametallic prosthesis have been used. With a satisfactory hip function the patient is--even 8 and a half years after the operation--able to walk and at work again.", "contents": "[Alloplastic reconstruction of the proximal third of the femur. Case report]. The case of a woman, aged 51, is reported. In this patient, in 1961, because of an alteration developed in the right neck of the femur--and trochanter area--diagnosed for osteoclastoma--irradiation treatment has been performed. After steadily increasing complaints the patient suffered in 1965 a pathological fracture. In 1966 after resection of the proximal third of the femurametallic prosthesis have been used. With a satisfactory hip function the patient is--even 8 and a half years after the operation--able to walk and at work again."}
{"id": "PMID:6841", "title": "Program for managing chronic pain. II. Short-term results.", "content": "A program for treating inpatients who had chronic pain resulted in significant improvement in 79% of them by the time of their dismissal. At the time of short-term follow-up (6 months), however, this improvement rate had diminished to 50%. It was observed that this type of chronically disabled person can return home and increase work-related activity without returning to previous patterns of drug use and repeated hospitalizations.", "contents": "Program for managing chronic pain. II. Short-term results. A program for treating inpatients who had chronic pain resulted in significant improvement in 79% of them by the time of their dismissal. At the time of short-term follow-up (6 months), however, this improvement rate had diminished to 50%. It was observed that this type of chronically disabled person can return home and increase work-related activity without returning to previous patterns of drug use and repeated hospitalizations."}
{"id": "PMID:6856", "title": "Enzymatic hydrolysis of 1-monoacyl-SN-glycerol-3-phosphoryl-choline (1-lysolecithin) by phospholipases from peanut seeds.", "content": "Hydrolysis of 1-lysolecithin (1-acyl glycerophosphorylcholine [1-acyl GPC]) by preparations of phospholipase D from peanut seeds was investigated. 1-Lysolecithin was hydrolyzed at a much slower rate than phosphatidylcholine (lecithin). Although Ca+2 ions are required for the cleavage of lecithin by the enzyme, their effect on the hydrolysis of lysolecithin depended upon the concentration of the substrate: at 0.2 mM 1-lysolecithin, Ca+2 ions increased the reaction rates, whereas at concentrations of the substrate lower than 0.1 mM, Ca+2 ions were inhibitory. A broad pH activity curve between 5 and 8 was obtained with higher rates in the alkaline range, both in the absence and presence of Ca+2 ions. The increased hydrolysis of lysolecithin due to Ca+2 was noticed over the entire pH range. Upon storage of the enzyme solutions at 4 C, decreased rates of hydrolysis of lecithin were observed, with t 1/2 values of ca. 50 and 100 days depending on the purity of the preparation. During the same period, no reduction occurred in the activity of these preparations on lysolecithin as substrate. The effects of Ca+2 ions and the analysis of the products of 1-acyl GPC cleavage by the enzyme preparations revealed the presence of more than one enzyme and the formation of the following compounds: lysophosphatidic acids (1 acyl glycerophosphoric acids), free fatty acids, glycerophosphorylcholine, and choline. The possible pathways leading to the degradation of lysolecithin and the formation of these products include reactions catalyzed by lysophospholipase A1 (lysophosphatidylcholine 1-acyl hydrolase, E.C. 3.1.1.5) and a phosphodiesterase (L-3-glycerylphosphorylcholine glycerophosphohydrolase, E.C.3.1.4.2), in addition to phospholipase D (phosphatidyl-choline phosphatidohydrolase, E.C. 3.1.4.4).", "contents": "Enzymatic hydrolysis of 1-monoacyl-SN-glycerol-3-phosphoryl-choline (1-lysolecithin) by phospholipases from peanut seeds. Hydrolysis of 1-lysolecithin (1-acyl glycerophosphorylcholine [1-acyl GPC]) by preparations of phospholipase D from peanut seeds was investigated. 1-Lysolecithin was hydrolyzed at a much slower rate than phosphatidylcholine (lecithin). Although Ca+2 ions are required for the cleavage of lecithin by the enzyme, their effect on the hydrolysis of lysolecithin depended upon the concentration of the substrate: at 0.2 mM 1-lysolecithin, Ca+2 ions increased the reaction rates, whereas at concentrations of the substrate lower than 0.1 mM, Ca+2 ions were inhibitory. A broad pH activity curve between 5 and 8 was obtained with higher rates in the alkaline range, both in the absence and presence of Ca+2 ions. The increased hydrolysis of lysolecithin due to Ca+2 was noticed over the entire pH range. Upon storage of the enzyme solutions at 4 C, decreased rates of hydrolysis of lecithin were observed, with t 1/2 values of ca. 50 and 100 days depending on the purity of the preparation. During the same period, no reduction occurred in the activity of these preparations on lysolecithin as substrate. The effects of Ca+2 ions and the analysis of the products of 1-acyl GPC cleavage by the enzyme preparations revealed the presence of more than one enzyme and the formation of the following compounds: lysophosphatidic acids (1 acyl glycerophosphoric acids), free fatty acids, glycerophosphorylcholine, and choline. The possible pathways leading to the degradation of lysolecithin and the formation of these products include reactions catalyzed by lysophospholipase A1 (lysophosphatidylcholine 1-acyl hydrolase, E.C. 3.1.1.5) and a phosphodiesterase (L-3-glycerylphosphorylcholine glycerophosphohydrolase, E.C.3.1.4.2), in addition to phospholipase D (phosphatidyl-choline phosphatidohydrolase, E.C. 3.1.4.4)."}
{"id": "PMID:6857", "title": "The potentialities of some antihistaminics in preanaesthetic medication.", "content": "A detailed study has been carried out on the potentialities of antazoline and chlorpheneramine (C.P.M.) in preanaesthetic medication. It included a determination of their sedative action, effects on cardiovascular system and any possible anticholinergic and antiarrhythmic properties. Both drugs depressed spontaneous activity in mice. Antazoline produced hypotension in chloralosed dogs and spinal cats (a peripheral action). Both produced a negative inotropic action on isolated rabbit's heart. On rat's auricle antazoline produced a positive chronotropic action while C.P.M. produced a negative chronotropic action. Both drugs could protect the heart against adrenaline induced arrhythmias during chloroform and halothane anaesthesia. Their anticholinergic properties were demonstrated by studies on isolated rabbit's heart and intestine as well as on isolated guinea pig's ileum.", "contents": "The potentialities of some antihistaminics in preanaesthetic medication. A detailed study has been carried out on the potentialities of antazoline and chlorpheneramine (C.P.M.) in preanaesthetic medication. It included a determination of their sedative action, effects on cardiovascular system and any possible anticholinergic and antiarrhythmic properties. Both drugs depressed spontaneous activity in mice. Antazoline produced hypotension in chloralosed dogs and spinal cats (a peripheral action). Both produced a negative inotropic action on isolated rabbit's heart. On rat's auricle antazoline produced a positive chronotropic action while C.P.M. produced a negative chronotropic action. Both drugs could protect the heart against adrenaline induced arrhythmias during chloroform and halothane anaesthesia. Their anticholinergic properties were demonstrated by studies on isolated rabbit's heart and intestine as well as on isolated guinea pig's ileum."}
{"id": "PMID:6862", "title": "[Classification of acute bacterial meningitis cases according to their etiology, seen in a children's hospital in Ankara from March 1973 to April 1974].", "content": "In a 14 months period, as from March 1973 to April 1974 468 cases of acute bacterial meningitis have been diagnosed by C.S.F. findings; namely by examining the protein and sugar content, by the cell counts, Gram's staining and culturing of the sediments of C.S.F. 188 cases were proven by culturing to be meningococcic meningitis. All these cases are from the families living in suburban areas of the city under crowded circumstances, which show the importance of population density in the epidemiology of this particular disease.", "contents": "[Classification of acute bacterial meningitis cases according to their etiology, seen in a children's hospital in Ankara from March 1973 to April 1974]. In a 14 months period, as from March 1973 to April 1974 468 cases of acute bacterial meningitis have been diagnosed by C.S.F. findings; namely by examining the protein and sugar content, by the cell counts, Gram's staining and culturing of the sediments of C.S.F. 188 cases were proven by culturing to be meningococcic meningitis. All these cases are from the families living in suburban areas of the city under crowded circumstances, which show the importance of population density in the epidemiology of this particular disease."}
{"id": "PMID:6860", "title": "[Yeast cell wall-dissolving enzymes of the thermotolerant actinomycete Thermoactinomyces vulgaris].", "content": "The thermotolerant culture of Thermoactinomyces vulgaris PA II-4A was cultivated in the Biotec fermenter to obtain the enzyme preparation with a high proteolytic and lytic activity. Resistance of the cells of Candida utilis and Saccharomyces fragilis (mesophilic and thermotolerant strains) to the lytic action of the enzyme preparation was different. Preliminary treatment of the yeast cells by L-cysteine increased their susceptibility to the lytic action of the preparation. The degree of lysis of the cells depended also on their age: the cells growing during 10-12 hours were lysed easier than the cells cultivated during 24 hours.", "contents": "[Yeast cell wall-dissolving enzymes of the thermotolerant actinomycete Thermoactinomyces vulgaris]. The thermotolerant culture of Thermoactinomyces vulgaris PA II-4A was cultivated in the Biotec fermenter to obtain the enzyme preparation with a high proteolytic and lytic activity. Resistance of the cells of Candida utilis and Saccharomyces fragilis (mesophilic and thermotolerant strains) to the lytic action of the enzyme preparation was different. Preliminary treatment of the yeast cells by L-cysteine increased their susceptibility to the lytic action of the preparation. The degree of lysis of the cells depended also on their age: the cells growing during 10-12 hours were lysed easier than the cells cultivated during 24 hours."}
{"id": "PMID:6861", "title": "[Cholesterol breakdown by enzyme preparations extracted from Streptomyces lavendulae].", "content": "Cholesterol was decomposed by 75-90% during two hours by enzyme preparations from the disintegrated mycelium of Streptomyces lavendulae. The effect of concentrations of cholesterol and protein on the decomposition of cholesterol by the enzyme was studied; the higher the content of protein in a sample, the more rapidly cholesterol is decomposed; the rate of cholesterol decomposition increases with a decrease of its concentration. The optimum pH is 7.5-9.0. After dialysis and lyophilization, the activity of the enzyme preparations remains the same during two weeks, and then decreases by a factor of 1.5-2 in the course of the following thirty days.", "contents": "[Cholesterol breakdown by enzyme preparations extracted from Streptomyces lavendulae]. Cholesterol was decomposed by 75-90% during two hours by enzyme preparations from the disintegrated mycelium of Streptomyces lavendulae. The effect of concentrations of cholesterol and protein on the decomposition of cholesterol by the enzyme was studied; the higher the content of protein in a sample, the more rapidly cholesterol is decomposed; the rate of cholesterol decomposition increases with a decrease of its concentration. The optimum pH is 7.5-9.0. After dialysis and lyophilization, the activity of the enzyme preparations remains the same during two weeks, and then decreases by a factor of 1.5-2 in the course of the following thirty days."}
{"id": "PMID:6865", "title": "Sulphasalazine lung.", "content": "A patient developed the rare complication of pulmonary eosinophilia whilst receiving sulphasalazine. A review of the world literature on sulphasalazine-induced lung disease is presented.", "contents": "Sulphasalazine lung. A patient developed the rare complication of pulmonary eosinophilia whilst receiving sulphasalazine. A review of the world literature on sulphasalazine-induced lung disease is presented."}
{"id": "PMID:6863", "title": "A tentative transmission mechanism for the twitch elicited in guinea-pig vas deferens by field stimulation.", "content": "The twitch response to nerve activity in the vas deferens does not behave as if it were adrenergic since it is enhanced by adrenoceptor blockers and often inhibited by noradrenaline and other sympathomimieic amines. Potassium (K+) ions have a strong reinforcing action on the twitch and easily restore it after blockade by lanthanum. The hypothesis is advanced that K+ ions have a transmitter function in the vas deferens and that K+ ions released in conjunction with the nerve stimulus may reach a concentration at the postsynaptic membrane sufficient to excite the muscle cell and produce a twitch.", "contents": "A tentative transmission mechanism for the twitch elicited in guinea-pig vas deferens by field stimulation. The twitch response to nerve activity in the vas deferens does not behave as if it were adrenergic since it is enhanced by adrenoceptor blockers and often inhibited by noradrenaline and other sympathomimieic amines. Potassium (K+) ions have a strong reinforcing action on the twitch and easily restore it after blockade by lanthanum. The hypothesis is advanced that K+ ions have a transmitter function in the vas deferens and that K+ ions released in conjunction with the nerve stimulus may reach a concentration at the postsynaptic membrane sufficient to excite the muscle cell and produce a twitch."}
{"id": "PMID:6867", "title": "[On the significance of beta-adrenergic stimuli for the gastric secretion in humans].", "content": "In adults of both sexes, the influence on the basal and the maximal by means of pentagastrin stimulated gastric secretion of a single intravenous injection of 8 mg (0.09 to 0.16 mg/kg) oxyfedrine or of two intramuscular injections of 1 mg (0.014 to 0.016 mg/kg) or of 2.5 mg (0.033 to 0.045 mg/kg) in each case isoproterenol, consecutively administered at an interval of 15 minutes, was studied. At a dose which evokes cardiovascular responses isoproterenol does not produce a significant change of the secretory rates of H+, C1-, Na+, K+, Ca++ and Mg++ or of the ionic composition of gastric juice both during basal and maximal acid output. Oxyfedrine shows only during maximal acid stimulation some effects on gastric secretion: a significant rise of the concentration and secretory rate of H+ and of the secretory rate of C1- and a significant decline of the concentration of Na+ and of both the concentration and secretory rate of Mg++. Beta-adrenergic receptors seem not to play any part in the regulation of the production of gastric juice. Possibly, the action of oxyfedrine on the stimulated gastric mucosa may be mediated by a stimulation of alpha-adrenergic receptors or by inhibition of the activity of 3',5'-AMP-phosphodiesterase.", "contents": "[On the significance of beta-adrenergic stimuli for the gastric secretion in humans]. In adults of both sexes, the influence on the basal and the maximal by means of pentagastrin stimulated gastric secretion of a single intravenous injection of 8 mg (0.09 to 0.16 mg/kg) oxyfedrine or of two intramuscular injections of 1 mg (0.014 to 0.016 mg/kg) or of 2.5 mg (0.033 to 0.045 mg/kg) in each case isoproterenol, consecutively administered at an interval of 15 minutes, was studied. At a dose which evokes cardiovascular responses isoproterenol does not produce a significant change of the secretory rates of H+, C1-, Na+, K+, Ca++ and Mg++ or of the ionic composition of gastric juice both during basal and maximal acid output. Oxyfedrine shows only during maximal acid stimulation some effects on gastric secretion: a significant rise of the concentration and secretory rate of H+ and of the secretory rate of C1- and a significant decline of the concentration of Na+ and of both the concentration and secretory rate of Mg++. Beta-adrenergic receptors seem not to play any part in the regulation of the production of gastric juice. Possibly, the action of oxyfedrine on the stimulated gastric mucosa may be mediated by a stimulation of alpha-adrenergic receptors or by inhibition of the activity of 3',5'-AMP-phosphodiesterase."}
{"id": "PMID:6900", "title": "[Beta-lactoglobulin AB fluorescence under different physico-chemical conditions. Denaturation by urea and organic solvents].", "content": "Dependences of different fluorescence parameters of bovine beta-lactoglobulin AB on the concentrations of urea (pH 2.8-8.8), ethanol (pH 2.1-10.2), and dioxane (pH 5.3) have been investigated. The denaturation properties (the free energy and the stoichiometry of denaturative interaction) are highly dependent on pH values. The data obtained indicate that the hydrophobic interactions are the determining forces in the stabilization process of the beta-lactoglobulin molecule. The relative contribution of these interactions lowers with pH rise. The denaturation of beta-lactoglobulin AB proceeds through two stages under conditions when the protein octamer exists. Up to 30 vol.% of ethanol and dioxane, the penetration of the organic molecules into the external parts of the protein globule takes place. At the concentration of the solvent exceeding 50 vol.% structural transitions are observed. The comparison of fluorescence and perturbation spectral data enables one to localise tryptophan residues in the protein more precisely. The results of this and former reports lead to hypothesis that beta-lactoglobulin may serve as a transporter of some substances which are unstable to acidic media.", "contents": "[Beta-lactoglobulin AB fluorescence under different physico-chemical conditions. Denaturation by urea and organic solvents]. Dependences of different fluorescence parameters of bovine beta-lactoglobulin AB on the concentrations of urea (pH 2.8-8.8), ethanol (pH 2.1-10.2), and dioxane (pH 5.3) have been investigated. The denaturation properties (the free energy and the stoichiometry of denaturative interaction) are highly dependent on pH values. The data obtained indicate that the hydrophobic interactions are the determining forces in the stabilization process of the beta-lactoglobulin molecule. The relative contribution of these interactions lowers with pH rise. The denaturation of beta-lactoglobulin AB proceeds through two stages under conditions when the protein octamer exists. Up to 30 vol.% of ethanol and dioxane, the penetration of the organic molecules into the external parts of the protein globule takes place. At the concentration of the solvent exceeding 50 vol.% structural transitions are observed. The comparison of fluorescence and perturbation spectral data enables one to localise tryptophan residues in the protein more precisely. The results of this and former reports lead to hypothesis that beta-lactoglobulin may serve as a transporter of some substances which are unstable to acidic media."}
{"id": "PMID:6901", "title": "[The compact form of DNA in solution. IV. The effect of secondary structure defectiveness on the arrangement of double-chained DNA molecules into compact particles].", "content": "Influence of pH on absorbance and CD-spectra of DNA in PEG-containing water-salt solutions has been studied. The changes in the spectra appeared due to disturbance of the DNA secondary structure upon acidification of the medium proir to or after DNA compactization. If acidification preceeds DNA compactization an intense negative band in the CD spectrum inherent to the compact particles is observed at pH values 7-4. The intensity of the band decreases with an increase of the acidity. The size of the compact particles as evaluated from the dependence of the apparent optical density on the wavelength value remains unchanged (about 1200 A). If the solution is strongly acidified (pH 4.0-2.8) and a considerable disturbance in the DNA secondary structure takes place a negative band in the CD spectrum completely disappears. If one acidifies a solution containing preformed DNA compact particles a decrease  of the intensity of the CD negative band starts at lower pH values (less than 2.8). This process is accompanied by an increase of the size of the particles. Acidic \"denaturation\" of DNA within the compact particles (pH approximately 2.5) is followed by a dissappearance of the CD negative band and a considerable increase of the particle size. The data obtained indicate that the specific arrangement of DNA strands manifested in a CD negative band depends on the defects in the DNA secondary structure.", "contents": "[The compact form of DNA in solution. IV. The effect of secondary structure defectiveness on the arrangement of double-chained DNA molecules into compact particles]. Influence of pH on absorbance and CD-spectra of DNA in PEG-containing water-salt solutions has been studied. The changes in the spectra appeared due to disturbance of the DNA secondary structure upon acidification of the medium proir to or after DNA compactization. If acidification preceeds DNA compactization an intense negative band in the CD spectrum inherent to the compact particles is observed at pH values 7-4. The intensity of the band decreases with an increase of the acidity. The size of the compact particles as evaluated from the dependence of the apparent optical density on the wavelength value remains unchanged (about 1200 A). If the solution is strongly acidified (pH 4.0-2.8) and a considerable disturbance in the DNA secondary structure takes place a negative band in the CD spectrum completely disappears. If one acidifies a solution containing preformed DNA compact particles a decrease  of the intensity of the CD negative band starts at lower pH values (less than 2.8). This process is accompanied by an increase of the size of the particles. Acidic \"denaturation\" of DNA within the compact particles (pH approximately 2.5) is followed by a dissappearance of the CD negative band and a considerable increase of the particle size. The data obtained indicate that the specific arrangement of DNA strands manifested in a CD negative band depends on the defects in the DNA secondary structure."}
{"id": "PMID:6902", "title": "[Kinetics and mechanism of inactivation of isolated chloroplasts].", "content": "A detailed kinetic analysis has been performed of a multistep inactivation of chloroplasts. The kinetic model suggested involves the formation of chloroplast forms differing in stability and activity. A comparison of the kinetic model with the experimental data shows that the mechanism of inactivation of isolated pea chloroplasts consists of at least two forms displaying different activity in the Hill reaction and different stability in solution. The effect was studied of the nature of the buffer and destruction products on the kinetics of chloroplast inactivation in the process of \"ageing\". In phosphate buffer, where the concentration of phosphate exceeds 40 mM, the effect of the destruction products of chloroplasts on their inactivation is insignificant. The pH dependence on the inactivation kinetics suggests that the pH region from 6 to 9 affects only the rapid kinetic process resulting in the increase in the chloroplast activity; irreversible inactivation of chloroplasts is pH-independent. The temperature dependence of the irreversible inactivation kinetics has been studied and the activation parametres of this stage have been determined. Possible molecular mechanism of the limiting stages of the inactivation of isolated chloroplasts are discussed, which can explain the kinetic data obtained.", "contents": "[Kinetics and mechanism of inactivation of isolated chloroplasts]. A detailed kinetic analysis has been performed of a multistep inactivation of chloroplasts. The kinetic model suggested involves the formation of chloroplast forms differing in stability and activity. A comparison of the kinetic model with the experimental data shows that the mechanism of inactivation of isolated pea chloroplasts consists of at least two forms displaying different activity in the Hill reaction and different stability in solution. The effect was studied of the nature of the buffer and destruction products on the kinetics of chloroplast inactivation in the process of \"ageing\". In phosphate buffer, where the concentration of phosphate exceeds 40 mM, the effect of the destruction products of chloroplasts on their inactivation is insignificant. The pH dependence on the inactivation kinetics suggests that the pH region from 6 to 9 affects only the rapid kinetic process resulting in the increase in the chloroplast activity; irreversible inactivation of chloroplasts is pH-independent. The temperature dependence of the irreversible inactivation kinetics has been studied and the activation parametres of this stage have been determined. Possible molecular mechanism of the limiting stages of the inactivation of isolated chloroplasts are discussed, which can explain the kinetic data obtained."}
{"id": "PMID:6909", "title": "Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship.", "content": "Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day). Neither had anemia or hepatic dysfunction, and serum vitamin B12 concentrations ranged from 369 to 800 pg per milliliter. The propositus, the younger brother, continued to excrete excessive methylmalonate, 103 to 115 mg per day, after 2000 mug of parenterally administered vitamin B12 at the fifth and 11th months of study. Leukocyte activities of the cobalamin-linked enzyme methylmalonyl coenzyme A mutase were respectively reduced in the propositus and his brother, to 0.04 and 0.11 nmoles of 3-(14)-C Ls methylmalonyl coenzyme A metabolized per hour per milligram of leukocyte protein (normal, 0.286 +/- 0.079 [S.D.]). These activities were not enhanced by 2 mug of 5'-deoxyadenosylcobalamin added to the assays. A heritable benign form of adult methylmalonic aciduria rather than vitamin B12 lack best explains these findings.", "contents": "Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship. Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day). Neither had anemia or hepatic dysfunction, and serum vitamin B12 concentrations ranged from 369 to 800 pg per milliliter. The propositus, the younger brother, continued to excrete excessive methylmalonate, 103 to 115 mg per day, after 2000 mug of parenterally administered vitamin B12 at the fifth and 11th months of study. Leukocyte activities of the cobalamin-linked enzyme methylmalonyl coenzyme A mutase were respectively reduced in the propositus and his brother, to 0.04 and 0.11 nmoles of 3-(14)-C Ls methylmalonyl coenzyme A metabolized per hour per milligram of leukocyte protein (normal, 0.286 +/- 0.079 [S.D.]). These activities were not enhanced by 2 mug of 5'-deoxyadenosylcobalamin added to the assays. A heritable benign form of adult methylmalonic aciduria rather than vitamin B12 lack best explains these findings."}
{"id": "PMID:6918", "title": "Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents.", "content": "The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones.", "contents": "Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones."}
{"id": "PMID:6919", "title": "Noradrenaline synthesis and utilization: control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents.", "content": "The changes in the synthesis and utilization or noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes. 1. Cranial to a lesion of the spinal cord, the alpha-methyltyrosine-induced disappearance of noradrenaline was accelerated by the alpha-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three alpha-adrenoreceptor blocking agents. 2. The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the alpha-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the alpha-adrenoreceptors regulating the release of noradrenaline induced by nerve impluses. 3. The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the popa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three alpha--adrenoreceptor blocking agents as well as by clonidine. 4. The results show that the synthesis and the utilization noradrenaline normally, as well as the accelerations of these processes by alpha-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might by influenced via the activity of teh alpha-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feedback mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline.", "contents": "Noradrenaline synthesis and utilization: control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents. The changes in the synthesis and utilization or noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes. 1. Cranial to a lesion of the spinal cord, the alpha-methyltyrosine-induced disappearance of noradrenaline was accelerated by the alpha-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three alpha-adrenoreceptor blocking agents. 2. The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the alpha-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the alpha-adrenoreceptors regulating the release of noradrenaline induced by nerve impluses. 3. The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the popa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three alpha--adrenoreceptor blocking agents as well as by clonidine. 4. The results show that the synthesis and the utilization noradrenaline normally, as well as the accelerations of these processes by alpha-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might by influenced via the activity of teh alpha-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feedback mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline."}
{"id": "PMID:6925", "title": "[Takayasu-Onishi arteritis. II. Relations of Takayasu-Onishi arteritis with other non-specific arteritides].", "content": "Takayasu-Onishi arteritis (T.O.) is similar to Hutchison-Horton arteritis (H.H.) on histological, clinical, laboratory, and pathogenetic grounds. Both probably depend on immunitary dysreactivity, their different clinical expression being attributable to differences in the district involved and the age of the subject. Both are preceded or accompanied by rheumatism. An interesting relation can be made out between temporal arteritis and \"rheumatic polymyalgia\" or, more aptly, \"rhizomelic polymyalgia\" (Ballabio, 1975). The latter (of rheumatic origin) may accompany arteritis - Hamrin, indeed, has suggested their unification in the description \"arteritic polymyalgia\". It is uncertain whether vasculopathy in the course of collagen disease, rheumatic arteritis, and polyarteritis nodosa can be identified with T.O., even though a common immunological basis can be made out. The difference between T.O. and thromboangiitis obliterans, on the other hand, is quite clear at the present time.", "contents": "[Takayasu-Onishi arteritis. II. Relations of Takayasu-Onishi arteritis with other non-specific arteritides]. Takayasu-Onishi arteritis (T.O.) is similar to Hutchison-Horton arteritis (H.H.) on histological, clinical, laboratory, and pathogenetic grounds. Both probably depend on immunitary dysreactivity, their different clinical expression being attributable to differences in the district involved and the age of the subject. Both are preceded or accompanied by rheumatism. An interesting relation can be made out between temporal arteritis and \"rheumatic polymyalgia\" or, more aptly, \"rhizomelic polymyalgia\" (Ballabio, 1975). The latter (of rheumatic origin) may accompany arteritis - Hamrin, indeed, has suggested their unification in the description \"arteritic polymyalgia\". It is uncertain whether vasculopathy in the course of collagen disease, rheumatic arteritis, and polyarteritis nodosa can be identified with T.O., even though a common immunological basis can be made out. The difference between T.O. and thromboangiitis obliterans, on the other hand, is quite clear at the present time."}
{"id": "PMID:6924", "title": "[Takayasu-Onishi arteritis. Current etiopathogenetic aspects].", "content": "By Takayasu-Onishi's arteritis is meant an arteritic process with unknown aetiology which electively affects young women, seemingly of prevalently Asiatic stock. The disease concerns almost exclusively large elastic arteries and presents clinically with early preocclusive symptomatology followed, after a varying period, by a picture of obstructive angiopathy. Here, the most recent aetiopathogenetic findings are considered. The disease's predilection for the young female, together with certain clinical and experimental observations, suggest that a dysendocrine condition may have some pathogenetic responsibility, at least in a favourable sense; this responsibility is documented by the finding of high levels of oestrogenuria during the entire cycle in patients suffering from the disease. On the other hand, the angiopathy localization in the large elastic arteries and in certain segments of the aortic arch and epiaortic trunks means that the role of topographic moments whould not be underestimated. As regards infectious factors, the tubercular and streptococcic continue to be of great importance even today. Neither acts directly, however, but by way of an abnormal immunitary reaction which they seem able to trigger off. The infectious moment would thus appear to be related to the immunitary moment, and the latter would seem to play the part of perpetuating the pathological vascular involvement promoted by contact of the organism with the aetiological agent.", "contents": "[Takayasu-Onishi arteritis. Current etiopathogenetic aspects]. By Takayasu-Onishi's arteritis is meant an arteritic process with unknown aetiology which electively affects young women, seemingly of prevalently Asiatic stock. The disease concerns almost exclusively large elastic arteries and presents clinically with early preocclusive symptomatology followed, after a varying period, by a picture of obstructive angiopathy. Here, the most recent aetiopathogenetic findings are considered. The disease's predilection for the young female, together with certain clinical and experimental observations, suggest that a dysendocrine condition may have some pathogenetic responsibility, at least in a favourable sense; this responsibility is documented by the finding of high levels of oestrogenuria during the entire cycle in patients suffering from the disease. On the other hand, the angiopathy localization in the large elastic arteries and in certain segments of the aortic arch and epiaortic trunks means that the role of topographic moments whould not be underestimated. As regards infectious factors, the tubercular and streptococcic continue to be of great importance even today. Neither acts directly, however, but by way of an abnormal immunitary reaction which they seem able to trigger off. The infectious moment would thus appear to be related to the immunitary moment, and the latter would seem to play the part of perpetuating the pathological vascular involvement promoted by contact of the organism with the aetiological agent."}
{"id": "PMID:6926", "title": "[Comparative evaluation of local 02 consumption in lumbar sympathetic infiltration as compared with acupuncture].", "content": "The effectiveness of acupuncture in the treatment of lower limb obliterating arteritis as an alternative to pharmacological sympatheticolumbar block was assessed by comparing local O2 consumption in the ischaemic extremity. It was found that both techniques lead to vasodilation sufficient to normalise local values. Acupuncture, however, has a more protracted effect up to 24 hr., as compared with only 12 hr after pharmacological block.", "contents": "[Comparative evaluation of local 02 consumption in lumbar sympathetic infiltration as compared with acupuncture]. The effectiveness of acupuncture in the treatment of lower limb obliterating arteritis as an alternative to pharmacological sympatheticolumbar block was assessed by comparing local O2 consumption in the ischaemic extremity. It was found that both techniques lead to vasodilation sufficient to normalise local values. Acupuncture, however, has a more protracted effect up to 24 hr., as compared with only 12 hr after pharmacological block."}
{"id": "PMID:6927", "title": "A survey of isolates of Streptococcus pneumoniae.", "content": "Over eight months 130 isolates of Streptococcus pneumoniae were examined for sensitivity to penicillin, tetracycline, cephalosporin and co-trimoxozole. Except in one doubtful case all isolates were sensitive to penicillin. All were sensitive to cephalosporin. 6.9 percent is isolates were resistant to co-trimoxozole. It is suggested that penicillin remains the drug of choice in the treatment of pneumococcal infections.", "contents": "A survey of isolates of Streptococcus pneumoniae. Over eight months 130 isolates of Streptococcus pneumoniae were examined for sensitivity to penicillin, tetracycline, cephalosporin and co-trimoxozole. Except in one doubtful case all isolates were sensitive to penicillin. All were sensitive to cephalosporin. 6.9 percent is isolates were resistant to co-trimoxozole. It is suggested that penicillin remains the drug of choice in the treatment of pneumococcal infections."}
{"id": "PMID:6929", "title": "[Acute hepatic porphyria as diagnostic problem in childhood (author's transl)].", "content": "Case report of a 12 year old girl with acute hepatic porphyria. The difficulties of diagnosis in childhood are discussed. No effective treatment is known. The importance of early diagnosis is emphasized, in order to avoid certain medicaments, stress situations etc., which can cause an acute attack of porphyria.", "contents": "[Acute hepatic porphyria as diagnostic problem in childhood (author's transl)]. Case report of a 12 year old girl with acute hepatic porphyria. The difficulties of diagnosis in childhood are discussed. No effective treatment is known. The importance of early diagnosis is emphasized, in order to avoid certain medicaments, stress situations etc., which can cause an acute attack of porphyria."}
{"id": "PMID:6928", "title": "Dibenzepin and amitriptyline in depressive states: comparative double-blind trial.", "content": "Dibenzepin and amitriptyline appeared to be equally efficacious in controlling target symptoms of depressive reactions. These results appear to be consistent with pharmacological profiles of the two drugs which are both tricylic compounds. Control of target symptoms occurred in an undulating and non-progressive manner in both groups. Aggravation of depressive symptomatology in the third week of treatment was noted in both groups and appeared to be clinically very important in the management of depressed patients. Dibenzepin caused relatively fewer side effects which appears to be an advantage over amitriptyline. Dibenzepin appeared to be a suitable alternative for amitriptyline intolerant patients, with moderately severe depression associated with anxiety, especially patients who demonstrated emotional sensitivity or passive dependent personality, and psychosomatic symptoms.", "contents": "Dibenzepin and amitriptyline in depressive states: comparative double-blind trial. Dibenzepin and amitriptyline appeared to be equally efficacious in controlling target symptoms of depressive reactions. These results appear to be consistent with pharmacological profiles of the two drugs which are both tricylic compounds. Control of target symptoms occurred in an undulating and non-progressive manner in both groups. Aggravation of depressive symptomatology in the third week of treatment was noted in both groups and appeared to be clinically very important in the management of depressed patients. Dibenzepin caused relatively fewer side effects which appears to be an advantage over amitriptyline. Dibenzepin appeared to be a suitable alternative for amitriptyline intolerant patients, with moderately severe depression associated with anxiety, especially patients who demonstrated emotional sensitivity or passive dependent personality, and psychosomatic symptoms."}
{"id": "PMID:6940", "title": "Acid-base curve nomogram for dog blood.", "content": "Pooled canine blood of different hemoglobin concentration was equilibrated with two carbon dioxide tensions and the resulting pH's of the samples were measured at 38 degrees C. Readings obtained provided data for the construction of a cartesian nomogram for the dog, based on the pH/log pCO2 coordinate system. The nomogram can be used to evaluate both respiratory and non-respiratory acid-base parameters. For contrast, a control nomogram on human blood was also constructed. Both nomograms show broad similarity. This is to be expected as the normal criteria used to define base excess relating to dog blood are the same as those used for human blood. Nonetheless, base excess and buffer base calculations using the nomogram for the dog and that for man show a deviation of 2.5-10%, and we consider this deviation to be more due to a species difference than to any summated experimental error.", "contents": "Acid-base curve nomogram for dog blood. Pooled canine blood of different hemoglobin concentration was equilibrated with two carbon dioxide tensions and the resulting pH's of the samples were measured at 38 degrees C. Readings obtained provided data for the construction of a cartesian nomogram for the dog, based on the pH/log pCO2 coordinate system. The nomogram can be used to evaluate both respiratory and non-respiratory acid-base parameters. For contrast, a control nomogram on human blood was also constructed. Both nomograms show broad similarity. This is to be expected as the normal criteria used to define base excess relating to dog blood are the same as those used for human blood. Nonetheless, base excess and buffer base calculations using the nomogram for the dog and that for man show a deviation of 2.5-10%, and we consider this deviation to be more due to a species difference than to any summated experimental error."}
{"id": "PMID:6950", "title": "The influence of neuromediators injected into nucleus caudatus on bioelectrical seizure activity of amygdala.", "content": "The influence of electrical and chemical stimulation of nucleus caudatus (NC) on bioelectrical seizure activity of amygdala (Am) was studied in rabbits. The electrical stimulation of NC inhibits seizures in Am induced by the administration of picrotoxin into this nucleus. Dopamine (DA) and cholinomimetics-metacholine and neostygmine-applied into NC inhibit seizures in Am. Noradrenaline (NA) acts biphasically, first potentiating and then inhibiting seizures in Am. Serotonin (5-HT) and glutamic acid (GA) administered to NC do not affect the seizures. In the case of seizures excited by electrical stimulation, DA and neostygmine possessed inhibiting action; NA, too, inhibited seizures without, however, inducing primary stimulation. Similarly as in the case of picrotoxin-stimulated seizures, neither 5-HT nor GA brought about the effects. The present study deals with the correlation of dopaminergic anc cholinergic systems in NC.", "contents": "The influence of neuromediators injected into nucleus caudatus on bioelectrical seizure activity of amygdala. The influence of electrical and chemical stimulation of nucleus caudatus (NC) on bioelectrical seizure activity of amygdala (Am) was studied in rabbits. The electrical stimulation of NC inhibits seizures in Am induced by the administration of picrotoxin into this nucleus. Dopamine (DA) and cholinomimetics-metacholine and neostygmine-applied into NC inhibit seizures in Am. Noradrenaline (NA) acts biphasically, first potentiating and then inhibiting seizures in Am. Serotonin (5-HT) and glutamic acid (GA) administered to NC do not affect the seizures. In the case of seizures excited by electrical stimulation, DA and neostygmine possessed inhibiting action; NA, too, inhibited seizures without, however, inducing primary stimulation. Similarly as in the case of picrotoxin-stimulated seizures, neither 5-HT nor GA brought about the effects. The present study deals with the correlation of dopaminergic anc cholinergic systems in NC."}
{"id": "PMID:6952", "title": "Changes in plasma electrolytes, acid-base balance and other physiological parameters of adult female turkeys under conditions of acute hyperthermia.", "content": "The effects of acute hyperthermia on certain physiological parameters of turkey hens was studied. It was found that the response of the turkey to hyperthermia is similar to the reported response of the chicken. The birds began panting and the average body temperature increased 0.1 degrees C. as the ambient temperature reached 32 degrees C. The panting or polypnea induced a profound respiratory alkalosis in the turkeys. The acute hyperthermia also caused a significant (P less than 0.05) decrease in plasma levels of sodium, total calcium, magnesium and inorganic phosphorus. The plasma level of potassium was significantly (P less than 0.05) increased.", "contents": "Changes in plasma electrolytes, acid-base balance and other physiological parameters of adult female turkeys under conditions of acute hyperthermia. The effects of acute hyperthermia on certain physiological parameters of turkey hens was studied. It was found that the response of the turkey to hyperthermia is similar to the reported response of the chicken. The birds began panting and the average body temperature increased 0.1 degrees C. as the ambient temperature reached 32 degrees C. The panting or polypnea induced a profound respiratory alkalosis in the turkeys. The acute hyperthermia also caused a significant (P less than 0.05) decrease in plasma levels of sodium, total calcium, magnesium and inorganic phosphorus. The plasma level of potassium was significantly (P less than 0.05) increased."}
{"id": "PMID:6953", "title": "Acid-base balance, plasma electrolytes and production performance of adult turkey hens under conditions of increasing ambient temperature.", "content": "Turkey hens were exposed to stepwise increases in ambient temperature from 21 degrees C. to 25 degrees C. to 30 degrees C. to 35 degrees C. at two-week intervals. Dietary calcium levels to 1.54, 2.01 and 2.48 percent were fed. Acid-base balance, plasma electrolytes and production performance were studied. The temperature increase caused a significant (P less than 0.05) decrease in plasma sodium, calcium, and magnesium, and in egg production, shell thickness and egg weight and a significant (P less than 0.05) increase in plasma potassium. There was no significant change in the acid-base balance of the blood as measured by blood PO2, PCO2 and pH. Egg production was not significantly correlated to blood gas activitelated to plasma calcium and magnesium levels. Dietary calcium levels had no influence on the parameters measured.", "contents": "Acid-base balance, plasma electrolytes and production performance of adult turkey hens under conditions of increasing ambient temperature. Turkey hens were exposed to stepwise increases in ambient temperature from 21 degrees C. to 25 degrees C. to 30 degrees C. to 35 degrees C. at two-week intervals. Dietary calcium levels to 1.54, 2.01 and 2.48 percent were fed. Acid-base balance, plasma electrolytes and production performance were studied. The temperature increase caused a significant (P less than 0.05) decrease in plasma sodium, calcium, and magnesium, and in egg production, shell thickness and egg weight and a significant (P less than 0.05) increase in plasma potassium. There was no significant change in the acid-base balance of the blood as measured by blood PO2, PCO2 and pH. Egg production was not significantly correlated to blood gas activitelated to plasma calcium and magnesium levels. Dietary calcium levels had no influence on the parameters measured."}
{"id": "PMID:6958", "title": "beta-Adrenergic blockade reduces the severity of acute renal failure in rats.", "content": "Propranolol administration in the hypoxic model of acute renal failure (ARF) in rats has reduced plasma renin activity (PRA) and uraemia as compared to untreated controls. P113 has no effect on uraemia but increased PRA in ARF. A combination of both drugs is no more effective in reducing uraemia than propranolol alone. These results support the view that beta-adrenergic blockade by propranolol reduces the severity of ARF by preventing the post-hypoxic release of renin.", "contents": "beta-Adrenergic blockade reduces the severity of acute renal failure in rats. Propranolol administration in the hypoxic model of acute renal failure (ARF) in rats has reduced plasma renin activity (PRA) and uraemia as compared to untreated controls. P113 has no effect on uraemia but increased PRA in ARF. A combination of both drugs is no more effective in reducing uraemia than propranolol alone. These results support the view that beta-adrenergic blockade by propranolol reduces the severity of ARF by preventing the post-hypoxic release of renin."}
{"id": "PMID:6954", "title": "[The effect of ACTH and several antimetabolites of vitamin B6 on the activity of tyrosine aminotransferase in the liver of intact and hypophysectomized rats].", "content": "ACTH injected intraperitoneally in a dose of 140 Units per 1 kg of body weight to intact rats or to rats subjected to hypophysectomy 24 hours before the experiment produced an increase in the activity of tyrosine-aminotrasferase in the liver (4.5 or 2.5 times, respectively) in comparison with the normal. D-cycloserine and its dimere injected intraperitoneally to the intact starving rats in a dose of 2.0-2.5 g per 1 kg of body weight produced in 4 hours a sharp elevation in the liver of the activity of tyrosine-amino transferase, whose induction constituted 75 and 180%, respectively. 24 hours after hypophysectomy D-cycloserine produced no induction of this enzyme in the rat liver; in difference from this, the D-cycloserine dimere produced an induced formation of tyrosine-aminotransferase (comparable with ACTH) in the liver of hypophysectomized rats. This indicated that the induction mechanism of tyrosine-aminotransferase in the liver of rats under the effect of D-cycloserine and its dimere differed.", "contents": "[The effect of ACTH and several antimetabolites of vitamin B6 on the activity of tyrosine aminotransferase in the liver of intact and hypophysectomized rats]. ACTH injected intraperitoneally in a dose of 140 Units per 1 kg of body weight to intact rats or to rats subjected to hypophysectomy 24 hours before the experiment produced an increase in the activity of tyrosine-aminotrasferase in the liver (4.5 or 2.5 times, respectively) in comparison with the normal. D-cycloserine and its dimere injected intraperitoneally to the intact starving rats in a dose of 2.0-2.5 g per 1 kg of body weight produced in 4 hours a sharp elevation in the liver of the activity of tyrosine-amino transferase, whose induction constituted 75 and 180%, respectively. 24 hours after hypophysectomy D-cycloserine produced no induction of this enzyme in the rat liver; in difference from this, the D-cycloserine dimere produced an induced formation of tyrosine-aminotransferase (comparable with ACTH) in the liver of hypophysectomized rats. This indicated that the induction mechanism of tyrosine-aminotransferase in the liver of rats under the effect of D-cycloserine and its dimere differed."}
{"id": "PMID:6959", "title": "Acute renal effects of new beta-adrenergic receptor site blocking agents on renal function.", "content": "The effects of two new beta blockers on renal function have been studied. There were significant decreases in urine flow, urea clearance, sodium and chloride excretion rates after acute administration. Fractional excretion of sodium (FeNa) fell significantly but did not continue to fall during chronic administration. Blood pressure and plasma renin activity decreased significantly after two months' therapy. These findings suggest that beta blockers in patients with unstable cardiovascular function increase the need for concomitant diuretic therapy.", "contents": "Acute renal effects of new beta-adrenergic receptor site blocking agents on renal function. The effects of two new beta blockers on renal function have been studied. There were significant decreases in urine flow, urea clearance, sodium and chloride excretion rates after acute administration. Fractional excretion of sodium (FeNa) fell significantly but did not continue to fall during chronic administration. Blood pressure and plasma renin activity decreased significantly after two months' therapy. These findings suggest that beta blockers in patients with unstable cardiovascular function increase the need for concomitant diuretic therapy."}
{"id": "PMID:6960", "title": "Interrelationships between Ca2+ and adenylate and guanylate cyclases in the control of platelet secretion and aggregation.", "content": "Ca2+ is a powerful inhibitor (Ki is congruent to 16 muM) of basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in membranes obtained from homogenized human platelets. Ca2+ (but not the ionophore A23,187) decreased V(max) of the reaction without an effect on the Ks for ATP. Neither ATP nor PGE1 affected Ki for Ca2+. In intact platelets A23,187 induced Ca2+ influx and markedly inhibited PGE1-stimulated rise in adenosine 3':5'-cyclic monophosphate (cAMP) levels. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2] activity was mainly found in the soluble fraction (greater than 90%). Both soluble and membrane bound enzymes were stimulated by Mn2+ and Ca2+ and inhibited by Zn2+. Adenylate and guanylate cyclase activity were both present in a membrane fraction cyclase activity were both present in a membrane fraction which contained Ca2+ activated ATPase activity, and accumulated Ca2+ from the medium in the presence of ATP and oxalate. Other evidence indicates that these membranes originated in large part from the dense tubular system of the platelets. It is proposed that concurrent inhibition of adenylate cyclase and stimulation of guanylate cyclase facilitates the direct initiating effect of Ca2+ on platelet secretion and aggregation.", "contents": "Interrelationships between Ca2+ and adenylate and guanylate cyclases in the control of platelet secretion and aggregation. Ca2+ is a powerful inhibitor (Ki is congruent to 16 muM) of basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in membranes obtained from homogenized human platelets. Ca2+ (but not the ionophore A23,187) decreased V(max) of the reaction without an effect on the Ks for ATP. Neither ATP nor PGE1 affected Ki for Ca2+. In intact platelets A23,187 induced Ca2+ influx and markedly inhibited PGE1-stimulated rise in adenosine 3':5'-cyclic monophosphate (cAMP) levels. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2] activity was mainly found in the soluble fraction (greater than 90%). Both soluble and membrane bound enzymes were stimulated by Mn2+ and Ca2+ and inhibited by Zn2+. Adenylate and guanylate cyclase activity were both present in a membrane fraction cyclase activity were both present in a membrane fraction which contained Ca2+ activated ATPase activity, and accumulated Ca2+ from the medium in the presence of ATP and oxalate. Other evidence indicates that these membranes originated in large part from the dense tubular system of the platelets. It is proposed that concurrent inhibition of adenylate cyclase and stimulation of guanylate cyclase facilitates the direct initiating effect of Ca2+ on platelet secretion and aggregation."}
{"id": "PMID:6961", "title": "The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles.", "content": "Membrane vesicles isolated from E. coli generate a trans-membrane proton gradient of 2 pH units under appropriate conditions when assayed by flow dialysis. Using the distribution of weak acids to measure the proton gradient (deltapH) and the distribution of the lipophilic cation triphenyl-methylphosphonium to measure the electrical potential across the membrane (delta psi), the vesicles are shown to generate an electrochemical proton gradient (deltamuH+) of approximately-180 mV at pH 5.5 in the presence of ascorbate and phenazine methosulfate, the major component of which is a deltapH of about -110mV. As external pH is increased, deltapH decreases, reaching 0 at pH 7.5 and above, while delta psi remains at about-75 mV and internal pH remains at pH 7.5. Moreover, the ability of various electron donors to drive transport is correlated with their ability to generate deltamuH+. In addition, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin. These data and others (manuscript in preparation) provide convincing support for the role of chemiosmotic phenomena in active transport.", "contents": "The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles. Membrane vesicles isolated from E. coli generate a trans-membrane proton gradient of 2 pH units under appropriate conditions when assayed by flow dialysis. Using the distribution of weak acids to measure the proton gradient (deltapH) and the distribution of the lipophilic cation triphenyl-methylphosphonium to measure the electrical potential across the membrane (delta psi), the vesicles are shown to generate an electrochemical proton gradient (deltamuH+) of approximately-180 mV at pH 5.5 in the presence of ascorbate and phenazine methosulfate, the major component of which is a deltapH of about -110mV. As external pH is increased, deltapH decreases, reaching 0 at pH 7.5 and above, while delta psi remains at about-75 mV and internal pH remains at pH 7.5. Moreover, the ability of various electron donors to drive transport is correlated with their ability to generate deltamuH+. In addition, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin. These data and others (manuscript in preparation) provide convincing support for the role of chemiosmotic phenomena in active transport."}
{"id": "PMID:6962", "title": "Observation of individual carboxyl groups in hen egg-white lysozyme by use of high field 13C-nuclear magnetic resonance.", "content": "Several of the carboxyl carbon atom resonances of hen egg-white lysozyme (mucopeptide N-acetylmuramoyl hydrolase, EC 3.2.1.17) have been resolved by 13C-nuclear magnetic resonance (NMR) at 68 MHz. The change in chemical shift of the carboxyl carbon atom resonances, as a function of pH, has enabled the distinction of these resonances against the background of many nontitrating carbonyl group resonances. Several apparent microscopic ionization constants have been determined from the carboxyl group NMR titration curves, and possible assignments are discussed. Preliminary experiments were carried out in the presence of cobaltous ion, and selective shifts of several resonances were observed. Our results indicate the possibility of the direct observation of a wide range of single functional groups of proteins in solution by NMR techniques.", "contents": "Observation of individual carboxyl groups in hen egg-white lysozyme by use of high field 13C-nuclear magnetic resonance. Several of the carboxyl carbon atom resonances of hen egg-white lysozyme (mucopeptide N-acetylmuramoyl hydrolase, EC 3.2.1.17) have been resolved by 13C-nuclear magnetic resonance (NMR) at 68 MHz. The change in chemical shift of the carboxyl carbon atom resonances, as a function of pH, has enabled the distinction of these resonances against the background of many nontitrating carbonyl group resonances. Several apparent microscopic ionization constants have been determined from the carboxyl group NMR titration curves, and possible assignments are discussed. Preliminary experiments were carried out in the presence of cobaltous ion, and selective shifts of several resonances were observed. Our results indicate the possibility of the direct observation of a wide range of single functional groups of proteins in solution by NMR techniques."}
{"id": "PMID:6963", "title": "Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis.", "content": "Sarcoidosis is a disease of unknown etiology that is characterized by the generalized formation of granulomas and is accompanied by elevation in the serum in less than half the patients of angiotensin converting enzyme, a dipeptidyl carboxypeptidase that catalyzes the conversion of the decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and L-histidyl-L-leucine. Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis. Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile. The data suggest that the granulomas in sarcoidosis may be the source of the elevated serum enzyme and that cells of the granulomas, particularly the epitheloid cells which appear by electron microscopy to have active protein biosynthesis, may be actively synthesizing the enzyme.", "contents": "Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis. Sarcoidosis is a disease of unknown etiology that is characterized by the generalized formation of granulomas and is accompanied by elevation in the serum in less than half the patients of angiotensin converting enzyme, a dipeptidyl carboxypeptidase that catalyzes the conversion of the decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and L-histidyl-L-leucine. Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis. Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile. The data suggest that the granulomas in sarcoidosis may be the source of the elevated serum enzyme and that cells of the granulomas, particularly the epitheloid cells which appear by electron microscopy to have active protein biosynthesis, may be actively synthesizing the enzyme."}
{"id": "PMID:6970", "title": "Nucleation of microbiologic calcification by proteolipid.", "content": "The component of crude phospholipid responsible for B. matruchotii calcification was isolated. Crude phospholipid, extracted from the microorganism, was separated into five fractions by column chromatography. A single, protein-containing fraction catalyzed apatite formation in a metastable calcium phosphate solution. The nucleating fraction was identified as a proteolipid.", "contents": "Nucleation of microbiologic calcification by proteolipid. The component of crude phospholipid responsible for B. matruchotii calcification was isolated. Crude phospholipid, extracted from the microorganism, was separated into five fractions by column chromatography. A single, protein-containing fraction catalyzed apatite formation in a metastable calcium phosphate solution. The nucleating fraction was identified as a proteolipid."}
{"id": "PMID:6971", "title": "Fractionation of serum transcobalamins on charged cellulose filters.", "content": "A simple and rapid fractionation procedure of the three transcobalamins, TCI, TCII, and TCII, of human serum was achieved by filtration through a stack of charged cellulose filters composed of one cellulose-nitrate and three DEAE-cellulose (DE-81) disks. A reaction mixture containing microliter amounts of serum was incubated with excess of 57Co B12 of high specific activity, diluted with 0.1 M sodium borate buffer (pH 8.5), and passed through the filter stack by applying vacuum. Under these conditions TCII is selectively and quantitatively adsorbed to the cellulose-nitrate filter while both TCI and TCIII adsorb to the DE-81 filters. In the second step TCIII is selectively desorbed from the latter filters by a 0.05 M monopotassium phosphate solution of pH 4.6. Using sera of different distribution of transcobalamins the data obtained were comparable to those determined by the more laborious methods employing DE-52 column chromatography combined with procedures to remove TCII.", "contents": "Fractionation of serum transcobalamins on charged cellulose filters. A simple and rapid fractionation procedure of the three transcobalamins, TCI, TCII, and TCII, of human serum was achieved by filtration through a stack of charged cellulose filters composed of one cellulose-nitrate and three DEAE-cellulose (DE-81) disks. A reaction mixture containing microliter amounts of serum was incubated with excess of 57Co B12 of high specific activity, diluted with 0.1 M sodium borate buffer (pH 8.5), and passed through the filter stack by applying vacuum. Under these conditions TCII is selectively and quantitatively adsorbed to the cellulose-nitrate filter while both TCI and TCIII adsorb to the DE-81 filters. In the second step TCIII is selectively desorbed from the latter filters by a 0.05 M monopotassium phosphate solution of pH 4.6. Using sera of different distribution of transcobalamins the data obtained were comparable to those determined by the more laborious methods employing DE-52 column chromatography combined with procedures to remove TCII."}
{"id": "PMID:6972", "title": "The inhibition by ADP of NADPH-supported adrenal steroid 11beta-hydroxylation.", "content": "The 11beta-hydroxylation of deoxycorticosterone to form corticosterone in adrenal mitochondria has been found to be inhibited by ADP and ATP, with ADP being the more inhibitory of the two. The evidence suggests that the ADP directly affects the enzyme system.", "contents": "The inhibition by ADP of NADPH-supported adrenal steroid 11beta-hydroxylation. The 11beta-hydroxylation of deoxycorticosterone to form corticosterone in adrenal mitochondria has been found to be inhibited by ADP and ATP, with ADP being the more inhibitory of the two. The evidence suggests that the ADP directly affects the enzyme system."}
{"id": "PMID:6973", "title": "The startle response in rats: effect of ethanol.", "content": "The effects of acute and chronic ethanol intake on the startle response was examined in male rats. Ethanol given IP produced a dose-dependent decrease in the amplitude of the startle response measured 30 min later. With a dose of 1 g/kg, the effect was evident at 15 min and had recovered substantially by 60 min. The effect of ethanol on the startle response was potentiated by pretreatment of the animals with pimozide, haloperidol, and p-chlorophenylalanine but not by propranolol, phenoxybenzamine, alpha-methyltyrosine, or pargyline. After 3 weeks on an ethanol-containing diet, the startle response was greater than that shown by rats on the control iso-caloric, sucrose-containing diet. After ethanol withdrawal, the startle response was further increased, with a peak about 9 to 12 hr after discontinuation of ethanol; thereafter, the response declined. This time course of heightened startle response during ethanol withdrawal corresponds to the time course of the activation of noradrenergic neurons during withdrawal. It appears that dopaminergic and serotonergic neurons are involved in the mediation of the startle response in rats.", "contents": "The startle response in rats: effect of ethanol. The effects of acute and chronic ethanol intake on the startle response was examined in male rats. Ethanol given IP produced a dose-dependent decrease in the amplitude of the startle response measured 30 min later. With a dose of 1 g/kg, the effect was evident at 15 min and had recovered substantially by 60 min. The effect of ethanol on the startle response was potentiated by pretreatment of the animals with pimozide, haloperidol, and p-chlorophenylalanine but not by propranolol, phenoxybenzamine, alpha-methyltyrosine, or pargyline. After 3 weeks on an ethanol-containing diet, the startle response was greater than that shown by rats on the control iso-caloric, sucrose-containing diet. After ethanol withdrawal, the startle response was further increased, with a peak about 9 to 12 hr after discontinuation of ethanol; thereafter, the response declined. This time course of heightened startle response during ethanol withdrawal corresponds to the time course of the activation of noradrenergic neurons during withdrawal. It appears that dopaminergic and serotonergic neurons are involved in the mediation of the startle response in rats."}
{"id": "PMID:6974", "title": "Plasma angiotensin II levels and water intake following beta-adrenergic stimulation, hypovolemia, cellular dehydration and water deprivation.", "content": "A comparison of the effects of extracellular and intracellular thirst stimuli on plasma levels of angiotensin II was made in rats. The administration of polyethylene glycol and isoproterenol elicited a strong drinking response and resulted in a significant increase in plasma angiotensin II. There was a significant correlation between the volume of water intake and plasma angiotensin II levels following the injection of polyethylene glycol but not following isoproterenol. Drinking was also elicited by the administration of hypertonic saline but there was no increase in plasma angiotensin II. The results suggest that endogenously released angiotensin II contributes to extracellular thirst but not to intracellular thirst.", "contents": "Plasma angiotensin II levels and water intake following beta-adrenergic stimulation, hypovolemia, cellular dehydration and water deprivation. A comparison of the effects of extracellular and intracellular thirst stimuli on plasma levels of angiotensin II was made in rats. The administration of polyethylene glycol and isoproterenol elicited a strong drinking response and resulted in a significant increase in plasma angiotensin II. There was a significant correlation between the volume of water intake and plasma angiotensin II levels following the injection of polyethylene glycol but not following isoproterenol. Drinking was also elicited by the administration of hypertonic saline but there was no increase in plasma angiotensin II. The results suggest that endogenously released angiotensin II contributes to extracellular thirst but not to intracellular thirst."}
{"id": "PMID:6975", "title": "Prevention of memory loss following puromycin treatment.", "content": "Female C57BL/6J mice were trained on a one trial passive avoidance response. Twenty-four hours later, they were treated with puromycin in combination with either 2.0 or 10.0 mg/kg of amphetamine, 0.3 mg/kg of strychnine, or 20.0 or 50.0 mg/kg of pentylenetetrazol. Tests one week after training revealed that treatment with these stimulant drugs prevented the memory loss characteristic of puromycin; an exception being those animals injected with the low dose of amphetamine. Biochemical determination of amino acid incorporation into protein revealed that none of the stimulant drugs used significantly altered the extent or the duration of protein synthesis inhibition induced by puromycin. These results are interpreted as showing that the amnesic effects of puromycin can be counteracted by a state of heightened nervous system excitation.", "contents": "Prevention of memory loss following puromycin treatment. Female C57BL/6J mice were trained on a one trial passive avoidance response. Twenty-four hours later, they were treated with puromycin in combination with either 2.0 or 10.0 mg/kg of amphetamine, 0.3 mg/kg of strychnine, or 20.0 or 50.0 mg/kg of pentylenetetrazol. Tests one week after training revealed that treatment with these stimulant drugs prevented the memory loss characteristic of puromycin; an exception being those animals injected with the low dose of amphetamine. Biochemical determination of amino acid incorporation into protein revealed that none of the stimulant drugs used significantly altered the extent or the duration of protein synthesis inhibition induced by puromycin. These results are interpreted as showing that the amnesic effects of puromycin can be counteracted by a state of heightened nervous system excitation."}
{"id": "PMID:6976", "title": "Selective depleting effect of syrosingopine on brain catecholamine levels with relation to morphine analgesia in the rat.", "content": "Reserpine was the most potent, rescinnamine the next and syrosingopine the weakest in the depleting effects on brain amines of rauwolfia alkaloids. After syrosingopine, brain dopamine (DA) was decreased to a smaller degree and with a shorter duration as compared with norepinephrine (NE) and serotonin (5-HT), whereas reserpine elicited a marked and long lasting reduction in these amines. Accordingly, syrosingopine induced a depletion of brain NE and 5-HT without alteration in brain DA content 2-4 days after administration. Repeated administrations of syrosingopine, 2 mg/kg daily for 2 or 4 days, resulted in similar alterations in brain amine levels. This selective depleting effect of syrosingopine on brain amines was potentiated by combined treatment with disulfiram or fusaric acid, a dopamine beta-hydroxylase inhibitor. Under the condition of selective depletion of brain amines induced by repeated administrations of syrosingopine, 2 mg/kg daily for 2 days, the analgesic action of morphine was not affected, whereas reserpine and tetrabenazine antagonized morphine analgesia, concomitant with inducing a depletion of all brain amines. The results suggest that brain DA may be more important than brain NE or 5-HT with regard to the mechanisms by which morpine produces analgesia.", "contents": "Selective depleting effect of syrosingopine on brain catecholamine levels with relation to morphine analgesia in the rat. Reserpine was the most potent, rescinnamine the next and syrosingopine the weakest in the depleting effects on brain amines of rauwolfia alkaloids. After syrosingopine, brain dopamine (DA) was decreased to a smaller degree and with a shorter duration as compared with norepinephrine (NE) and serotonin (5-HT), whereas reserpine elicited a marked and long lasting reduction in these amines. Accordingly, syrosingopine induced a depletion of brain NE and 5-HT without alteration in brain DA content 2-4 days after administration. Repeated administrations of syrosingopine, 2 mg/kg daily for 2 or 4 days, resulted in similar alterations in brain amine levels. This selective depleting effect of syrosingopine on brain amines was potentiated by combined treatment with disulfiram or fusaric acid, a dopamine beta-hydroxylase inhibitor. Under the condition of selective depletion of brain amines induced by repeated administrations of syrosingopine, 2 mg/kg daily for 2 days, the analgesic action of morphine was not affected, whereas reserpine and tetrabenazine antagonized morphine analgesia, concomitant with inducing a depletion of all brain amines. The results suggest that brain DA may be more important than brain NE or 5-HT with regard to the mechanisms by which morpine produces analgesia."}
{"id": "PMID:6977", "title": "Nuclear dna amounts in angiosperms.", "content": "The number of angiosperm species for which nuclear DNA amount estimates have been made has nearly trebled since the last collected lists of such values were published, and therefore, publication of a more comprehensive list is over due. This paper lists absolute nuclear DNA amounts for 753 angiosperm species. The dats were assembled primarily for reference purposes, and so the species are listed in alphabetical order, as this was felt to be more helpful to cyto- and biochemists whom, it is anticipated, will be among its major users. The paper also reviews aspects of the history, nomenclature, methods, accuracy and problems of nuclear DNA estimation in angiosperms. No attempt is made to reconsider those aspects of nuclear DNA estimation which have been fully revised previously, although the bibliography of such aspects is given. Instead, the paper is intended as a source of basic information regarding the terminology, practice and limitations of nuclear DNA estimation, especially by Feulgen microdensitometry, as currently practiced.", "contents": "Nuclear dna amounts in angiosperms. The number of angiosperm species for which nuclear DNA amount estimates have been made has nearly trebled since the last collected lists of such values were published, and therefore, publication of a more comprehensive list is over due. This paper lists absolute nuclear DNA amounts for 753 angiosperm species. The dats were assembled primarily for reference purposes, and so the species are listed in alphabetical order, as this was felt to be more helpful to cyto- and biochemists whom, it is anticipated, will be among its major users. The paper also reviews aspects of the history, nomenclature, methods, accuracy and problems of nuclear DNA estimation in angiosperms. No attempt is made to reconsider those aspects of nuclear DNA estimation which have been fully revised previously, although the bibliography of such aspects is given. Instead, the paper is intended as a source of basic information regarding the terminology, practice and limitations of nuclear DNA estimation, especially by Feulgen microdensitometry, as currently practiced."}
{"id": "PMID:6982", "title": "Electrophysiology of mammalian gland cells.", "content": "The resting cell membrane potential varies from -40 to -70 mV according to type of gland cell and species. The RP depends mainly on the large transmembrane concentration gradient for K maintained by a pump mechanism extruding Na and accumulating K. Since the Na permeability (PNa) is much smaller than PK, the Na concentration gradient is less important. In addition to the dominant electrodiffusional control of RP the Na pump itself contributes since the active transport of Na (out) exceeds that of the active K uptake. Gland cells are generally electrically coupled--i.e., the junctional membrane resistance is much lower than the surface membrane resistance. The coupling may be widespread (e.g., liver) or confined to one acinus (e.g., salivary gland and pancreas). The specific surface cell membrane resistance may be about 2000 omega cm2. A number of neurotransmitters and hormones control cellular transport processes by their action on surface cell membrane receptors. Agonist-receptor interaction causes prominent changes in membrane potential and resistance, in many cases of a complex nature. Most gland cell membranes so far investigated in detail appear to be electrically inexcitable; i.e., stimulation does not cause the appearance of action potentials (e.g., salivary glands, exocrine pancreas, and liver) but prominent exceptions to this are the endocrine pancreas (beta-cells) and the adrenal cortex. The main importance of agonist-induced membrane permeability changes is to alter the intracellular ion activities. An increase in [Na+] seems to be important whenever stimulation results in fluid transport and an increase in [Ca2+] triggers exocytosis.", "contents": "Electrophysiology of mammalian gland cells. The resting cell membrane potential varies from -40 to -70 mV according to type of gland cell and species. The RP depends mainly on the large transmembrane concentration gradient for K maintained by a pump mechanism extruding Na and accumulating K. Since the Na permeability (PNa) is much smaller than PK, the Na concentration gradient is less important. In addition to the dominant electrodiffusional control of RP the Na pump itself contributes since the active transport of Na (out) exceeds that of the active K uptake. Gland cells are generally electrically coupled--i.e., the junctional membrane resistance is much lower than the surface membrane resistance. The coupling may be widespread (e.g., liver) or confined to one acinus (e.g., salivary gland and pancreas). The specific surface cell membrane resistance may be about 2000 omega cm2. A number of neurotransmitters and hormones control cellular transport processes by their action on surface cell membrane receptors. Agonist-receptor interaction causes prominent changes in membrane potential and resistance, in many cases of a complex nature. Most gland cell membranes so far investigated in detail appear to be electrically inexcitable; i.e., stimulation does not cause the appearance of action potentials (e.g., salivary glands, exocrine pancreas, and liver) but prominent exceptions to this are the endocrine pancreas (beta-cells) and the adrenal cortex. The main importance of agonist-induced membrane permeability changes is to alter the intracellular ion activities. An increase in [Na+] seems to be important whenever stimulation results in fluid transport and an increase in [Ca2+] triggers exocytosis."}
{"id": "PMID:6983", "title": "Breast sensation before and after plastic surgery.", "content": "Patients undergoing various plastic surgical procedures on their breasts were studied before and after operations with respect to sensation from crude touch, light pressure, and pain. The more extensive the operation on the breast (the more skin and breast tissue removed) the greater the postoperative decrease in sensation. Reduction mammaplasty and subcutaneous mastectomy were associated with decreased sensation in a significant number of patients. An unexpected finding was that patients having augmentation mammaplasty by either the inframammary or areola route showed a significant decrease in sensation to the nipple and apeola. At two years, 15 percent of the patients still had impaired sensory perception, although crude touch and light pressure appreciation had returned. Many of these patients had normal erectility with normal, and even enhanced, sensuality.", "contents": "Breast sensation before and after plastic surgery. Patients undergoing various plastic surgical procedures on their breasts were studied before and after operations with respect to sensation from crude touch, light pressure, and pain. The more extensive the operation on the breast (the more skin and breast tissue removed) the greater the postoperative decrease in sensation. Reduction mammaplasty and subcutaneous mastectomy were associated with decreased sensation in a significant number of patients. An unexpected finding was that patients having augmentation mammaplasty by either the inframammary or areola route showed a significant decrease in sensation to the nipple and apeola. At two years, 15 percent of the patients still had impaired sensory perception, although crude touch and light pressure appreciation had returned. Many of these patients had normal erectility with normal, and even enhanced, sensuality."}
{"id": "PMID:6985", "title": "Exposure in vivo of agoraphobics: contributions of diazepam, group exposure, and anxiety evocation.", "content": "Fifty-seven chronic agoraphobic outpatients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure, group versus individual exposure, and high versus medium anxiety arousal during individual exposure. The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up. Assessment was blind with respect to drug and psychological treatment. Patients in all treatment conditions improved significantly in phobias and in related life areas. Outcome to group exposure on phobias and other measures was similar in all three drug conditions (placebo, waning diazepam, peak diazepam) with no significant differences between them. Diazepam patients had significantly less discomfort than placebo patients during group exposure treatment. Group exposure patients improved slightly but significantly more than individual exposure patients on non-phobic measures, though group exposure was accompanied by more panics during treatment yet was easier to run by the therapist. Individual exposure under high anxiety arousal was no more therapeutic than with lower anxiety. Diazepam is a mild palliative during group exposure but does not facilitate outcome to treatment. Group exposure in vivo is mildly facilitatory for outcome compared with individual exposure. Anxiety evocation during treatment was not therapeutically helpful.", "contents": "Exposure in vivo of agoraphobics: contributions of diazepam, group exposure, and anxiety evocation. Fifty-seven chronic agoraphobic outpatients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure, group versus individual exposure, and high versus medium anxiety arousal during individual exposure. The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up. Assessment was blind with respect to drug and psychological treatment. Patients in all treatment conditions improved significantly in phobias and in related life areas. Outcome to group exposure on phobias and other measures was similar in all three drug conditions (placebo, waning diazepam, peak diazepam) with no significant differences between them. Diazepam patients had significantly less discomfort than placebo patients during group exposure treatment. Group exposure patients improved slightly but significantly more than individual exposure patients on non-phobic measures, though group exposure was accompanied by more panics during treatment yet was easier to run by the therapist. Individual exposure under high anxiety arousal was no more therapeutic than with lower anxiety. Diazepam is a mild palliative during group exposure but does not facilitate outcome to treatment. Group exposure in vivo is mildly facilitatory for outcome compared with individual exposure. Anxiety evocation during treatment was not therapeutically helpful."}
{"id": "PMID:6991", "title": "The regulation of physiological changes during mammalian aging.", "content": "Much evidence suggests that intrinsic molecular or cellular aging mechanisms need not be invoked to explain most age-related cellular changes and pathologcical conditions. Analysis of a widely scattered literature indicates that hormones and neural factors regulate a great number of cellular aging phenomena of mammals. It is proposed that age-related changes after maturation result from an extension of the neural and endocrine mechanisms that control earlier development and that produce a regulatory cascade of changing neural, endocrine, and target-tissue interactions.", "contents": "The regulation of physiological changes during mammalian aging. Much evidence suggests that intrinsic molecular or cellular aging mechanisms need not be invoked to explain most age-related cellular changes and pathologcical conditions. Analysis of a widely scattered literature indicates that hormones and neural factors regulate a great number of cellular aging phenomena of mammals. It is proposed that age-related changes after maturation result from an extension of the neural and endocrine mechanisms that control earlier development and that produce a regulatory cascade of changing neural, endocrine, and target-tissue interactions."}
{"id": "PMID:7001", "title": "Prenatal reserpine administration: permanent changes in adrenal tyrosine hydroxylase and dopamine beta-hydroxylase.", "content": "Reserpine (1 mg/kg) was administered to pregnant rats on days 12, 13 and 14 of gestation. Although adrenal tyrosine hydroxylase and dopamine beta-hydroxylase activities were normal in the offspring at 4 days of postnatal age, both were elevated by 17 days and the elevations persisted into adulthood. The changes may result from permanently increased sympatho-adrenal stimulation.", "contents": "Prenatal reserpine administration: permanent changes in adrenal tyrosine hydroxylase and dopamine beta-hydroxylase. Reserpine (1 mg/kg) was administered to pregnant rats on days 12, 13 and 14 of gestation. Although adrenal tyrosine hydroxylase and dopamine beta-hydroxylase activities were normal in the offspring at 4 days of postnatal age, both were elevated by 17 days and the elevations persisted into adulthood. The changes may result from permanently increased sympatho-adrenal stimulation."}
{"id": "PMID:7002", "title": "Comparison of triazolam and methyprylon as a hypnotic in insomniacs.", "content": "The hypnotic effect of a new triazolobenzodiazepine, triazolam (0.5 mg) and methyprylon was compared in 30 outpatient volunteers with insomnia using the preference technique. On the first night of the 2 night trial, triazolam or methyprylon was given on a double-blind basis and on the 2nd night the outpatients received the alternate medication. Following each trial night the patients were interviewed in regard to their sleep. Of the 28 patients who completed the study, 21 patients preferred triazolam, 5 preferred methyprylon and 2 had no preference (p = 0.001). Analysis of the various sleep parameters showed that triazolam helped the patients sleep more than methyprylon (p = 0.026), there were fewer awakenings on triazolam (p = 0.064), a longer duration of sleep (p = 0.064) and a better feeling in the a.m. (p = 0.020). The sleep onset was the same after both medications. The number and severity of the side effects was considerably higher after methyprylon.", "contents": "Comparison of triazolam and methyprylon as a hypnotic in insomniacs. The hypnotic effect of a new triazolobenzodiazepine, triazolam (0.5 mg) and methyprylon was compared in 30 outpatient volunteers with insomnia using the preference technique. On the first night of the 2 night trial, triazolam or methyprylon was given on a double-blind basis and on the 2nd night the outpatients received the alternate medication. Following each trial night the patients were interviewed in regard to their sleep. Of the 28 patients who completed the study, 21 patients preferred triazolam, 5 preferred methyprylon and 2 had no preference (p = 0.001). Analysis of the various sleep parameters showed that triazolam helped the patients sleep more than methyprylon (p = 0.026), there were fewer awakenings on triazolam (p = 0.064), a longer duration of sleep (p = 0.064) and a better feeling in the a.m. (p = 0.020). The sleep onset was the same after both medications. The number and severity of the side effects was considerably higher after methyprylon."}
{"id": "PMID:7003", "title": "The effect of butaclamol and of other neuroleptic agents on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity.", "content": "The effects of the two enantiomers of butaclamol and of several neuroleptics on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity was investigated. The (+) but not the (-) enantiomer of butaclamol reverses the apomorphine-elicited enzyme inhibition. (+) Butaclamol is more potent than the other tested neuroleptics. All the tested neuroleptics reverse the apomorphine-elicited enzyme inhibition but their relative potency differs. Using two criteria, namely the concentrations of neuroleptics required to reverse enzyme inhibition maximally or by 25%, the order of decreasing potency is as follows: (+) butaclamol, fluphenazine, haloperidol, pimozide, chlorpromazine. The results suggest that the reversal of apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity is a valid test model for screening antipsychotic drugs.", "contents": "The effect of butaclamol and of other neuroleptic agents on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. The effects of the two enantiomers of butaclamol and of several neuroleptics on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity was investigated. The (+) but not the (-) enantiomer of butaclamol reverses the apomorphine-elicited enzyme inhibition. (+) Butaclamol is more potent than the other tested neuroleptics. All the tested neuroleptics reverse the apomorphine-elicited enzyme inhibition but their relative potency differs. Using two criteria, namely the concentrations of neuroleptics required to reverse enzyme inhibition maximally or by 25%, the order of decreasing potency is as follows: (+) butaclamol, fluphenazine, haloperidol, pimozide, chlorpromazine. The results suggest that the reversal of apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity is a valid test model for screening antipsychotic drugs."}
{"id": "PMID:7005", "title": "Subsynaptosomal distribution, inhibition, and characterization of the binding of (14C) 5-OH-indole-3-acetaldehyde to brain preparations.", "content": "The distribution of the monoamine oxidase (MAO) dependent binding of [14C] serotonin as well as of pre-formed [14C] 5-OH-indole-3-acetaldehyde to synaptic subfractions paralleled the gross distribution of MAO. The binding of [14C] serotonin and MAO activity in brain preparations was inhibited by CNS antidepressants (imipramine) or stimulants (caffeine), by hallucinogens (N,N-dimethyltryptamine), sedatives (chlorpromazine), and other drugs. The protein-lipid nature of the binding macromolecule was determined. The chemical nature of the acceptors was also investigated. Experiments with sodium borohydride indicated the partial formation of imines, those with SH-reactive compounds showed partial involvement of acceptor-SH groups in the binding.", "contents": "Subsynaptosomal distribution, inhibition, and characterization of the binding of (14C) 5-OH-indole-3-acetaldehyde to brain preparations. The distribution of the monoamine oxidase (MAO) dependent binding of [14C] serotonin as well as of pre-formed [14C] 5-OH-indole-3-acetaldehyde to synaptic subfractions paralleled the gross distribution of MAO. The binding of [14C] serotonin and MAO activity in brain preparations was inhibited by CNS antidepressants (imipramine) or stimulants (caffeine), by hallucinogens (N,N-dimethyltryptamine), sedatives (chlorpromazine), and other drugs. The protein-lipid nature of the binding macromolecule was determined. The chemical nature of the acceptors was also investigated. Experiments with sodium borohydride indicated the partial formation of imines, those with SH-reactive compounds showed partial involvement of acceptor-SH groups in the binding."}
{"id": "PMID:7006", "title": "Respiratory failure: correlation between encephalopathy, blood gases and blood ammonia.", "content": "In 59 patients with respiratory insufficiency due to chronic obstructive pulmonary disease (COPD) the relationship between the state of consciousness, the blood gases and blood ammonia were studied. Interindividually, a significant correlation was found between the encephalopathy and SaO2, PaCO2 or ammonia, and also between the blood gases and ammonia. On the other hand, an intraindividual study, performed on patients with minor cerebral dysfunction, showed that only PaCO2 was significantly correlated with the stage of consciousness. Ammonia did not appear to have a neurotoxic influence. The ammonia level seemed to be influenced primarily by other factors than the blood gases, although there was a borderline influence of SaO2 on aterial ammonia and a significant influence of PaCO2-HCO3 and pH on venous ammonia.", "contents": "Respiratory failure: correlation between encephalopathy, blood gases and blood ammonia. In 59 patients with respiratory insufficiency due to chronic obstructive pulmonary disease (COPD) the relationship between the state of consciousness, the blood gases and blood ammonia were studied. Interindividually, a significant correlation was found between the encephalopathy and SaO2, PaCO2 or ammonia, and also between the blood gases and ammonia. On the other hand, an intraindividual study, performed on patients with minor cerebral dysfunction, showed that only PaCO2 was significantly correlated with the stage of consciousness. Ammonia did not appear to have a neurotoxic influence. The ammonia level seemed to be influenced primarily by other factors than the blood gases, although there was a borderline influence of SaO2 on aterial ammonia and a significant influence of PaCO2-HCO3 and pH on venous ammonia."}
{"id": "PMID:7007", "title": "Effect of ascaris extract applied intravenously, on segment bronchus and the influence of ipsilateral vagus blockade.", "content": "Respiratory hypersensitivity and systemic effects after local application of Ascaris suum extract on the segmental bronchus and after its intravenous infusion are studied on four boxer dogs. Influence of ipsilateral vagus blockade on the respiratory hyperreactivity after intrabronchial application of ascaris was also investigated on the same dogs. Ascaris extract was applied in liquid form directly through a catheter into the right segmental bronchus. Egg albumin was applied in the same way for control. Local application of ascaris was repeated after ipsilateral central vagus blockade and once more after recovering vagus effect by lavage. At the end of the experiments ascaris extract was infused intravenously. The parameters studied were: deltaP(oes) mm Hg/100 ml TV (as a measurement of flow resistance in the airways), respiratory rates, arterial blood gases and pH, heart frequency, systemic blood pressure and histamine concentration per milliliter of plasma. All the animals presented a remarkable respiratory distress with local ascaris application, which could be clearly avoided with ipsilateral central vagus blockade. This respiratory hyperreactivity was not observed after intravenous infusion of ascaris extract, but a significant systemic effect, which was not the case after local application, could be observed.", "contents": "Effect of ascaris extract applied intravenously, on segment bronchus and the influence of ipsilateral vagus blockade. Respiratory hypersensitivity and systemic effects after local application of Ascaris suum extract on the segmental bronchus and after its intravenous infusion are studied on four boxer dogs. Influence of ipsilateral vagus blockade on the respiratory hyperreactivity after intrabronchial application of ascaris was also investigated on the same dogs. Ascaris extract was applied in liquid form directly through a catheter into the right segmental bronchus. Egg albumin was applied in the same way for control. Local application of ascaris was repeated after ipsilateral central vagus blockade and once more after recovering vagus effect by lavage. At the end of the experiments ascaris extract was infused intravenously. The parameters studied were: deltaP(oes) mm Hg/100 ml TV (as a measurement of flow resistance in the airways), respiratory rates, arterial blood gases and pH, heart frequency, systemic blood pressure and histamine concentration per milliliter of plasma. All the animals presented a remarkable respiratory distress with local ascaris application, which could be clearly avoided with ipsilateral central vagus blockade. This respiratory hyperreactivity was not observed after intravenous infusion of ascaris extract, but a significant systemic effect, which was not the case after local application, could be observed."}
{"id": "PMID:7008", "title": "A simple method for the determination of the thread-forming property of tracheobronchial secretions.", "content": "A method is described for determining the thread-forming property ('Spinnbarkeit') of tracheobronchial secretions. With this method it was observed that adrenergic compounds increase the length of the mucus threads by an average of 154% whereas mucolytic agents caused an average decrease of 63% in the length of the mucus threads.", "contents": "A simple method for the determination of the thread-forming property of tracheobronchial secretions. A method is described for determining the thread-forming property ('Spinnbarkeit') of tracheobronchial secretions. With this method it was observed that adrenergic compounds increase the length of the mucus threads by an average of 154% whereas mucolytic agents caused an average decrease of 63% in the length of the mucus threads."}
{"id": "PMID:7009", "title": "Changes in skeletal muscle cell pH during graded changes in PCO2.", "content": "Blood perfusing isolated dog gracilis muscles was equilibrated with CO2 tensions ranging from 30 to 120 mm Hg, resulting in venous P CO2 from 35 to 135 mm Hg. Extracellular pH values ranged from 6.96 to 7.41, and muscle cell pH, calculated from DMO distribution, ranged from 6.64 to 6.94. When intracellular pH was plotted as a function of the corresponding extracellular pH, a linear relationship (r = 0.92) was observed throughout the entire pH range. The slope deltapHi/deltapHe was 0.64, without evidence of a difference in slope at different pH values. These results do not support the previous observations in rat diaphragms that cell pH is not affected by PCO2 changes over a certain extracellular pH range. pHe was 0.64, without evidence of a difference in slope at different pH values. Theses results do not support the previous observations in rat diaphragms that cell pH is not affected by PCO2 changes over a certain extracellular pH range.", "contents": "Changes in skeletal muscle cell pH during graded changes in PCO2. Blood perfusing isolated dog gracilis muscles was equilibrated with CO2 tensions ranging from 30 to 120 mm Hg, resulting in venous P CO2 from 35 to 135 mm Hg. Extracellular pH values ranged from 6.96 to 7.41, and muscle cell pH, calculated from DMO distribution, ranged from 6.64 to 6.94. When intracellular pH was plotted as a function of the corresponding extracellular pH, a linear relationship (r = 0.92) was observed throughout the entire pH range. The slope deltapHi/deltapHe was 0.64, without evidence of a difference in slope at different pH values. These results do not support the previous observations in rat diaphragms that cell pH is not affected by PCO2 changes over a certain extracellular pH range. pHe was 0.64, without evidence of a difference in slope at different pH values. Theses results do not support the previous observations in rat diaphragms that cell pH is not affected by PCO2 changes over a certain extracellular pH range."}
{"id": "PMID:7010", "title": "Intracellular and extracellular acid-base changes in hemorrhagic shock.", "content": "Each of 21 dogs was bled until mean arterial blood pressure fell to 50 torr; this hemorrhagic shock state was then maintained for two hours. During hemorrhagic shock, the blood lactate concentration increased sixfold. The severe metabolic acidosis in arterial blood was partially compensated by a decreased PCO2 caused by increased ventilation. However, in mixed venous blood, the metabolic acidosis was combined with a respiratory acidosis. This hypercapnia in venous blood was indicative of the increased PCO2 in tissues poorly perfused following hemorrhage. The increase in the PCO2 of the femoral venous blood was greater than that in mixed venous blood, suggesting that some tissue beds were better perfused than those of the hind limb during shock. The intracellular lactate concentration of hind limb skeletal muscle was greatly increased in the shock state, and tissue PCO2 rose. Intracellular pH of skeletal muscle was only slightly decreased and bicarbonate concentration was unchanged during this combined metabolic and respiratory acidosis. This capacity of skeletal muscle to maintain a high HCO-3 concentration in intracellular fluid during metabolic acidosis may be an enhanced response of the mechanism responsible for maintaining (HCO-3)i normally at a level approximately ten times that which would be expected if HCO-3 were distributed passively.", "contents": "Intracellular and extracellular acid-base changes in hemorrhagic shock. Each of 21 dogs was bled until mean arterial blood pressure fell to 50 torr; this hemorrhagic shock state was then maintained for two hours. During hemorrhagic shock, the blood lactate concentration increased sixfold. The severe metabolic acidosis in arterial blood was partially compensated by a decreased PCO2 caused by increased ventilation. However, in mixed venous blood, the metabolic acidosis was combined with a respiratory acidosis. This hypercapnia in venous blood was indicative of the increased PCO2 in tissues poorly perfused following hemorrhage. The increase in the PCO2 of the femoral venous blood was greater than that in mixed venous blood, suggesting that some tissue beds were better perfused than those of the hind limb during shock. The intracellular lactate concentration of hind limb skeletal muscle was greatly increased in the shock state, and tissue PCO2 rose. Intracellular pH of skeletal muscle was only slightly decreased and bicarbonate concentration was unchanged during this combined metabolic and respiratory acidosis. This capacity of skeletal muscle to maintain a high HCO-3 concentration in intracellular fluid during metabolic acidosis may be an enhanced response of the mechanism responsible for maintaining (HCO-3)i normally at a level approximately ten times that which would be expected if HCO-3 were distributed passively."}
{"id": "PMID:7011", "title": "Extracellular and intracellular pH with changes of temperature in the dogfish Scyliorhinus stellaris.", "content": "Larger Spotted Dogfish, Scyliorhinus stellaris, were exposed to varied ambient temperature (t) in order to determine the behavior of extracellular pH (pHe), Pco2 and bicarbonate concentration as well as intracellular pH (pHi) in three muscle types. pHe was found to vary with temperature slightly less than expected on the basis of the rule of constant relative alkalinity in juvenile (deltapH/deltat= -0.0148 per degree centigrade) as well as in adult (deltapH/deltat= -0.0136) fish. The absolute pHe values of adult fish were about 0.08 pH units higher than in juvenile fish. Arterial pco2 increased with rising temperature, the increase being much more marked in adult than in juvenile fish. Extracellular bicarbonate concentration (calculated from the pH and Pco2 values measured in arterial blood) was not maintained constant, but diminished in juvenile and increased in adult fish with increasing temperature, indicating that extracellular pH in dogfish is regulated by variations of both Pco2 and bicarbonate concentration. Variations of intracellular pH with temperature (deltapHi/deltat), -0.0178 for white muscle, -0.0334 for red muscle, and -0.0098 for heart muscle, were significantly different from the values of the extracellular compartment and, except for white muscle, significantly different from the condition for constant relative alkalinity (deltapH/deltat= -0.0183). These results are in agreement with the rule of constant relative alkalinity with respect to extracellular pH and possibly also with respect to an overall mean intracellular pH, but the rule is not quantitatively followed by the individual body compartments and tissues.", "contents": "Extracellular and intracellular pH with changes of temperature in the dogfish Scyliorhinus stellaris. Larger Spotted Dogfish, Scyliorhinus stellaris, were exposed to varied ambient temperature (t) in order to determine the behavior of extracellular pH (pHe), Pco2 and bicarbonate concentration as well as intracellular pH (pHi) in three muscle types. pHe was found to vary with temperature slightly less than expected on the basis of the rule of constant relative alkalinity in juvenile (deltapH/deltat= -0.0148 per degree centigrade) as well as in adult (deltapH/deltat= -0.0136) fish. The absolute pHe values of adult fish were about 0.08 pH units higher than in juvenile fish. Arterial pco2 increased with rising temperature, the increase being much more marked in adult than in juvenile fish. Extracellular bicarbonate concentration (calculated from the pH and Pco2 values measured in arterial blood) was not maintained constant, but diminished in juvenile and increased in adult fish with increasing temperature, indicating that extracellular pH in dogfish is regulated by variations of both Pco2 and bicarbonate concentration. Variations of intracellular pH with temperature (deltapHi/deltat), -0.0178 for white muscle, -0.0334 for red muscle, and -0.0098 for heart muscle, were significantly different from the values of the extracellular compartment and, except for white muscle, significantly different from the condition for constant relative alkalinity (deltapH/deltat= -0.0183). These results are in agreement with the rule of constant relative alkalinity with respect to extracellular pH and possibly also with respect to an overall mean intracellular pH, but the rule is not quantitatively followed by the individual body compartments and tissues."}
{"id": "PMID:7012", "title": "Importance of changes in plasma HCO-3 on regulation of CSF HCO-3 in respiratory alkalosis.", "content": "In respiratory alkalosis the fall in CSF bicarbonate is in part due to increased CSF lactate. The rest of CSF HCO3 fall may be actively regulated or as more recent evidence suggests is dependent on plasma HCO3 fall. Therefore, the relationship between plasma and CSF HCO3 changes was studied during 4 hours of respiratory alkalosis (PaCO2=20 mm Hg) in anesthetized dogs when plasma HCO3: (1) fell normally, (2) kept 'normal' by NaHCO3 infusion, (3) increased by infusing more NaHCO3, and (4) reduced by infusing HCl. In respiratory alkalosis plasma and CSF HCO3 fell 4.6 and 3.8 mEQ/L, respectively. In hypocapnia and 'normal' plasma HCO3 CSF HCO3 fell 2 mEq/L and lactate increased 1.33 mEq/L. In hypocapnia and metabolic alkalosis plasma HCO3 increased 6.5 mEq/L and CSF HCO3 remained unchanged and lactate increased 2.12 mEq/L. In combined hypocapnia and metabolic acidosis plasma HCO3 fall 10.5 mEq/L but CSF HCO3 fell 3.1 mEq/L and CSF pH returned to normal at 4 hours. Therefore CSF HCO3 fall in hypocapnia is primarily and critically dependent on the simultaneous fall in plasma HCO3 content, with a minimal contribution from CNS lactate increase. When CSF PH has returned to normal, however, CSF HCO3 fall is stopped despite further falls in plasma HCO3.", "contents": "Importance of changes in plasma HCO-3 on regulation of CSF HCO-3 in respiratory alkalosis. In respiratory alkalosis the fall in CSF bicarbonate is in part due to increased CSF lactate. The rest of CSF HCO3 fall may be actively regulated or as more recent evidence suggests is dependent on plasma HCO3 fall. Therefore, the relationship between plasma and CSF HCO3 changes was studied during 4 hours of respiratory alkalosis (PaCO2=20 mm Hg) in anesthetized dogs when plasma HCO3: (1) fell normally, (2) kept 'normal' by NaHCO3 infusion, (3) increased by infusing more NaHCO3, and (4) reduced by infusing HCl. In respiratory alkalosis plasma and CSF HCO3 fell 4.6 and 3.8 mEQ/L, respectively. In hypocapnia and 'normal' plasma HCO3 CSF HCO3 fell 2 mEq/L and lactate increased 1.33 mEq/L. In hypocapnia and metabolic alkalosis plasma HCO3 increased 6.5 mEq/L and CSF HCO3 remained unchanged and lactate increased 2.12 mEq/L. In combined hypocapnia and metabolic acidosis plasma HCO3 fall 10.5 mEq/L but CSF HCO3 fell 3.1 mEq/L and CSF pH returned to normal at 4 hours. Therefore CSF HCO3 fall in hypocapnia is primarily and critically dependent on the simultaneous fall in plasma HCO3 content, with a minimal contribution from CNS lactate increase. When CSF PH has returned to normal, however, CSF HCO3 fall is stopped despite further falls in plasma HCO3."}
{"id": "PMID:7016", "title": "Cholinergic changes during conditioned suppression in rats.", "content": "Levels of acetylcholine were significantly elevated in the telencephalon and diencephalon + mesencephalon of rats killed by near-freezing during conditioned suppression of food-reinforced lever pressing, whereas levels of serotonin, dopamine, and norepinephrine were not altered. These neurochemical changes were not seen in rats serving as controls for conditioning experience, activity levels, or stimulus presentation.", "contents": "Cholinergic changes during conditioned suppression in rats. Levels of acetylcholine were significantly elevated in the telencephalon and diencephalon + mesencephalon of rats killed by near-freezing during conditioned suppression of food-reinforced lever pressing, whereas levels of serotonin, dopamine, and norepinephrine were not altered. These neurochemical changes were not seen in rats serving as controls for conditioning experience, activity levels, or stimulus presentation."}
{"id": "PMID:7014", "title": "[Treatment of anxiety in Parkinson's disease with bromazepam].", "content": "The Authors observe that anxiety is a rather frequent symptom in parkinsonian patients. The possible mechanisms are reviewed. In a double blind cross-over trial, a new antianxiety agent (Lexotan, Roche) was compared with Placebo, to delineate the therapeutic effect in anxious parkinsonian patients. A noteworthy activity was shown by the active drug, while after Placebo a deterioration of anxiety was demonstrated. Tremor was also alleviated by Lexotan and the importance of emotional troubles on tremor seems to be confirmed.", "contents": "[Treatment of anxiety in Parkinson's disease with bromazepam]. The Authors observe that anxiety is a rather frequent symptom in parkinsonian patients. The possible mechanisms are reviewed. In a double blind cross-over trial, a new antianxiety agent (Lexotan, Roche) was compared with Placebo, to delineate the therapeutic effect in anxious parkinsonian patients. A noteworthy activity was shown by the active drug, while after Placebo a deterioration of anxiety was demonstrated. Tremor was also alleviated by Lexotan and the importance of emotional troubles on tremor seems to be confirmed."}
{"id": "PMID:7025", "title": "Drug-induced handwriting changes: an empirical review.", "content": "Since handwriting is a highly complex, coordinated motor activity, handwrits of pharmacological agents. Its potential has been most evident in research involving therapeutic administrations of anti-psychotic an  anti-Parkinsonian drugs, from which consistent and systematic handwriting changes have been observed. This relationship has been found to be particularly significant among the anti-psychotics, since the onset of these graphomotor alterations appear to mark the optmal dose of the drug. Consistent and systematic handwriting changes have not been as evident in inivestigations of drugs used in a nontherapeutic atmosphere. Psychiatric assessments of subjects in ths type of research provided data which indicated that psychological stability may be a factor influencing the susceptibility of one's handwriting to drug induced changes.", "contents": "Drug-induced handwriting changes: an empirical review. Since handwriting is a highly complex, coordinated motor activity, handwrits of pharmacological agents. Its potential has been most evident in research involving therapeutic administrations of anti-psychotic an  anti-Parkinsonian drugs, from which consistent and systematic handwriting changes have been observed. This relationship has been found to be particularly significant among the anti-psychotics, since the onset of these graphomotor alterations appear to mark the optmal dose of the drug. Consistent and systematic handwriting changes have not been as evident in inivestigations of drugs used in a nontherapeutic atmosphere. Psychiatric assessments of subjects in ths type of research provided data which indicated that psychological stability may be a factor influencing the susceptibility of one's handwriting to drug induced changes."}
{"id": "PMID:7032", "title": "Organic dyestuffs as catalysts for fuel cells.", "content": "Electrocatalysis in fuel cells requires as well substances capable of catalyzing the anodic oxidation of fuels as catalysts for the cathodic reduction of oxygen. Several dyestuffs that catalyze oxygen reduction are known, but up to now only one has been described as active in anodic reactions. All these dyestuffs are N4-chelates. Comparative studies have shown that chelates with other types of coordination, in particular N202-, 04-, N2S2- and S4-chelates, are able to catalyze the reduction of oxygen, though they are considerably less active than the N4-compounds. With a given type of coordination, the nature of the central atom has a decisive influence on the catalytic activity of the dyestuff, whereas substitution on the organic skeleton has only a slight effect. Thermal pretreatment of the N4-chelates can considerably increase their stability in electrolytes containing sulfuric acid. All the experimental results point to the conclusion that, with electrocatalysts, as with natural oxygen carriers, the interaction essential for catalysis takes place between the oxygen and the central metal ion. Various assumptions may be made as to the nature of the rate-determining step. The cathodic reduction of oxygen can be regarded as redox catalysis, or it can be considered from the standpoint of molecular orbital theory. The models hitherto suggested for the mechanism of oxygen reduction are tested against the experimental results and a modified model based on MO theory is put forward.", "contents": "Organic dyestuffs as catalysts for fuel cells. Electrocatalysis in fuel cells requires as well substances capable of catalyzing the anodic oxidation of fuels as catalysts for the cathodic reduction of oxygen. Several dyestuffs that catalyze oxygen reduction are known, but up to now only one has been described as active in anodic reactions. All these dyestuffs are N4-chelates. Comparative studies have shown that chelates with other types of coordination, in particular N202-, 04-, N2S2- and S4-chelates, are able to catalyze the reduction of oxygen, though they are considerably less active than the N4-compounds. With a given type of coordination, the nature of the central atom has a decisive influence on the catalytic activity of the dyestuff, whereas substitution on the organic skeleton has only a slight effect. Thermal pretreatment of the N4-chelates can considerably increase their stability in electrolytes containing sulfuric acid. All the experimental results point to the conclusion that, with electrocatalysts, as with natural oxygen carriers, the interaction essential for catalysis takes place between the oxygen and the central metal ion. Various assumptions may be made as to the nature of the rate-determining step. The cathodic reduction of oxygen can be regarded as redox catalysis, or it can be considered from the standpoint of molecular orbital theory. The models hitherto suggested for the mechanism of oxygen reduction are tested against the experimental results and a modified model based on MO theory is put forward."}
{"id": "PMID:7033", "title": "Japanese encephalitis virus from pigs and mosquitoes in Jakarta, Indonesia.", "content": "Japanese encephalitis virus was isolated from 11 pools of Culex tritaeniorhynchus and a single pool of C. gelidus mosquitoes at a pig-raising area near Jakarta, West Java, Indonesia, during 1972-74. Ten sentinel pigs placed in the area all developed haemagglutination-inhibition antibodies against Japanese encephalitis and the virus was isolated from the blood of 3.", "contents": "Japanese encephalitis virus from pigs and mosquitoes in Jakarta, Indonesia. Japanese encephalitis virus was isolated from 11 pools of Culex tritaeniorhynchus and a single pool of C. gelidus mosquitoes at a pig-raising area near Jakarta, West Java, Indonesia, during 1972-74. Ten sentinel pigs placed in the area all developed haemagglutination-inhibition antibodies against Japanese encephalitis and the virus was isolated from the blood of 3."}
{"id": "PMID:7034", "title": "Acute graft-versus-host reaction in mice. I. Cellular events.", "content": "Cellular events in the spleen during the development of acute GvH reaction in lethally irradiated recipients of allogeneic lymphocytes may be divided into 6 interrelated processes: (1) entering and lodging in the spleen of about 17% of inoculated cells which forms the compartment of potentially reactive cells; (2) transformation (recruitment) of about 30% of cells lodged in the spleen into large pyroninophilic cells (LPC), a process lasting about 12-16 hr; (3) proliferation of recruited LPC by five successive divisions with a Tc of about 12 hr; (4) transformation of LPC into non-LPC; (5) proliferation of non-LPC by one division, with a Tc of about 8 hr; and (6) migration of mature immunologically active cells from the spleen. The last process correlates well with the concomitant appearance of lymphocytes in the peripheral blood (killer cells) and with the time of acute death among inoculated mice.", "contents": "Acute graft-versus-host reaction in mice. I. Cellular events. Cellular events in the spleen during the development of acute GvH reaction in lethally irradiated recipients of allogeneic lymphocytes may be divided into 6 interrelated processes: (1) entering and lodging in the spleen of about 17% of inoculated cells which forms the compartment of potentially reactive cells; (2) transformation (recruitment) of about 30% of cells lodged in the spleen into large pyroninophilic cells (LPC), a process lasting about 12-16 hr; (3) proliferation of recruited LPC by five successive divisions with a Tc of about 12 hr; (4) transformation of LPC into non-LPC; (5) proliferation of non-LPC by one division, with a Tc of about 8 hr; and (6) migration of mature immunologically active cells from the spleen. The last process correlates well with the concomitant appearance of lymphocytes in the peripheral blood (killer cells) and with the time of acute death among inoculated mice."}
{"id": "PMID:7035", "title": "Avoidance of graft versus host reactions in cured W-anemic mice.", "content": "Graft-versus-host reactions of parental cells in F1 hybrids were studied with two unrelated inbred strains of mice that differed at the mouse histocompatibility locus. W-anemic F1 recipients were compared with lethally irradiated normal F1 recipients. Both sets of recipients were populated by marrow and spleen cell grafts from parental and F1 donors. Most W-anemic F1 recipients were cured by parental and F1 cell grafts (except B6 spleen). Even after 13 to 18 months, they showed little or no effect from GVH reactions. Lethally irradiated normal F1 recipients tolerated parental marrow grafts almost as well, but gave dramatically different results with parental spleen grafts. Seventy-nine of 80 irradiated F1 recipients of parental spleen grafts died within 1 month. Unlike lethally irradiated recipients, W-anemic recipients have substantial numbers of their own cells along with the donor cells in their lymphoid tissues. These F1 lymphocytes may interact with parental lymphocytes in vivo to restrain reactions against F1 allogeneic antigens.", "contents": "Avoidance of graft versus host reactions in cured W-anemic mice. Graft-versus-host reactions of parental cells in F1 hybrids were studied with two unrelated inbred strains of mice that differed at the mouse histocompatibility locus. W-anemic F1 recipients were compared with lethally irradiated normal F1 recipients. Both sets of recipients were populated by marrow and spleen cell grafts from parental and F1 donors. Most W-anemic F1 recipients were cured by parental and F1 cell grafts (except B6 spleen). Even after 13 to 18 months, they showed little or no effect from GVH reactions. Lethally irradiated normal F1 recipients tolerated parental marrow grafts almost as well, but gave dramatically different results with parental spleen grafts. Seventy-nine of 80 irradiated F1 recipients of parental spleen grafts died within 1 month. Unlike lethally irradiated recipients, W-anemic recipients have substantial numbers of their own cells along with the donor cells in their lymphoid tissues. These F1 lymphocytes may interact with parental lymphocytes in vivo to restrain reactions against F1 allogeneic antigens."}
{"id": "PMID:7040", "title": "[Values of acid-base equilibrium in the blood of various species of domestic animals].", "content": "By means of the Astrup equilibration method the values of the acid-base balance of the blood were determined in 104 cows, 99 horses, 100 pigs, 15 sheep, 20 goats, and in 101 dogs. The pH values of the blood, the partial pressure of CO2, the base excess, the base buffer, the standard bicarbonate, the actual bicarbonate, and the total CO2 were processed statistically and are presented in tables.", "contents": "[Values of acid-base equilibrium in the blood of various species of domestic animals]. By means of the Astrup equilibration method the values of the acid-base balance of the blood were determined in 104 cows, 99 horses, 100 pigs, 15 sheep, 20 goats, and in 101 dogs. The pH values of the blood, the partial pressure of CO2, the base excess, the base buffer, the standard bicarbonate, the actual bicarbonate, and the total CO2 were processed statistically and are presented in tables."}
{"id": "PMID:7043", "title": "Species and phenobarbitone-induced differences in the kinetic constants of liver microsomal harmine O-demethylation.", "content": "1. The apparent kinetic constants for the O-demethylation of harmine to harmol by 10 000 g supernatant fractions from livers of mice, rats, guinea-pigs, rabbits, cats and cows have been determined. The Km values were 10-39 muM and Vmax 0-25 and 1-65 nmol/mg protein/min. 2. Optimal conditions of incubation time and NADP requirements differed between species. In all species except cat and cow the rate of O-demethylation of harmine was linear for 5 min, but in the latter species was linear for 15 min. Maximum stimulation of O-demethylation occurred at NADP concn. of between 50 and 375 muM. 3. Phenobarbitone pre-treatment of weanling, young adult and mature adult mice increased the Vmax for O-demethylation by 2.9- to 4.6-fold but did not change Km. Increased Vmax values were greatest in young and least in old mice and these changes were directly correlated with a decrease of hexobarbitone sleeping time.", "contents": "Species and phenobarbitone-induced differences in the kinetic constants of liver microsomal harmine O-demethylation. 1. The apparent kinetic constants for the O-demethylation of harmine to harmol by 10 000 g supernatant fractions from livers of mice, rats, guinea-pigs, rabbits, cats and cows have been determined. The Km values were 10-39 muM and Vmax 0-25 and 1-65 nmol/mg protein/min. 2. Optimal conditions of incubation time and NADP requirements differed between species. In all species except cat and cow the rate of O-demethylation of harmine was linear for 5 min, but in the latter species was linear for 15 min. Maximum stimulation of O-demethylation occurred at NADP concn. of between 50 and 375 muM. 3. Phenobarbitone pre-treatment of weanling, young adult and mature adult mice increased the Vmax for O-demethylation by 2.9- to 4.6-fold but did not change Km. Increased Vmax values were greatest in young and least in old mice and these changes were directly correlated with a decrease of hexobarbitone sleeping time."}
{"id": "PMID:7056", "title": "Severe urticaria caused by a moth Euproctis sp. (Lepidoptera: Lymantriidae).", "content": "The urticating hairs of a moth Euproctis sp., were found to be the cause of a severe urticarial and pruritic rash in an expatriate family. Such incidents are probably not uncommon in Papua New Guinea, and are best solved by destroying the food tree of the caterpillars where this is feasible.", "contents": "Severe urticaria caused by a moth Euproctis sp. (Lepidoptera: Lymantriidae). The urticating hairs of a moth Euproctis sp., were found to be the cause of a severe urticarial and pruritic rash in an expatriate family. Such incidents are probably not uncommon in Papua New Guinea, and are best solved by destroying the food tree of the caterpillars where this is feasible."}
{"id": "PMID:7057", "title": "[Transparency of analytical results found by different methods of electrophoresis studies on casein (author's transl)].", "content": "The electrophoretic mobility of the major casein components has been studied on different carriers. Besides free electrophoresis and paper electrophoresis starch gel, polyacrylamide gel and cellulose acetate gel have compared. With urea buffer mixtures of neutral to alkaline pH a mobility scale on all gels was found corresponding the order alphas-, beta-, kappa-, gamma-casein in the sense of decreasing mobility. The application of commercially available cellulose acetate strips for the investigation of genetic material in large numbers has been found to be sufficient. The transparency of polyacrylamide gel, starch gel and cellulose acetate gel results is guaranteed.", "contents": "[Transparency of analytical results found by different methods of electrophoresis studies on casein (author's transl)]. The electrophoretic mobility of the major casein components has been studied on different carriers. Besides free electrophoresis and paper electrophoresis starch gel, polyacrylamide gel and cellulose acetate gel have compared. With urea buffer mixtures of neutral to alkaline pH a mobility scale on all gels was found corresponding the order alphas-, beta-, kappa-, gamma-casein in the sense of decreasing mobility. The application of commercially available cellulose acetate strips for the investigation of genetic material in large numbers has been found to be sufficient. The transparency of polyacrylamide gel, starch gel and cellulose acetate gel results is guaranteed."}
{"id": "PMID:7058", "title": "[Behaviour of aflatoxin during production of processed cheese (author's transl)].", "content": "The problem of aflatoxin determination in processed cheese can be solved by the destruction of the emulsion with 6 m urea solution; the detection limit is 0.1-0.05 ppb B1 respectively G1. Examination of 115 trade samples resulted in 2 positive processed cheese samples only. This result cannot be reffered to the destruction of aflatoxins by the melting process, because neither at melting temperatures of 80-138 degrees C nor by melting salts and pH adjustments considerable losses could be observed, mostly below 5%.", "contents": "[Behaviour of aflatoxin during production of processed cheese (author's transl)]. The problem of aflatoxin determination in processed cheese can be solved by the destruction of the emulsion with 6 m urea solution; the detection limit is 0.1-0.05 ppb B1 respectively G1. Examination of 115 trade samples resulted in 2 positive processed cheese samples only. This result cannot be reffered to the destruction of aflatoxins by the melting process, because neither at melting temperatures of 80-138 degrees C nor by melting salts and pH adjustments considerable losses could be observed, mostly below 5%."}
{"id": "PMID:7059", "title": "The nitrosation products of creatine and creatinine in model systems.", "content": "The formation of N-nitrososarcosine from creatine, creatinine-5-oxime and l-methylhydantoin-5-oxime from creatinine was investigated in model solutions under various conditions (temperature, pH, concentration of sodium nitrite). N-nitrososarcosine was formed from creatine only in strongly acidic medium and its concentration increased with temperature and concentration of sodium nitrite. No N-nitrososarcosine was detected at 0 degrees C and in the presence of an equimolar amount of sodium nitrite. Creatinine-5-oxime and l-methylhydantoin-5-oxime was formed from creatinine in a broad region of pH, the highest concentration of these compounds was found in pH 3.6. The main reaction product was l-methylhydantoin-5-oxime. At a given pH, the concentrations of these two oximes increased generally with increased temperature and/or concentration of sodium nitrite. No oxime were detected at O degrees C and in the presence of equimolar amounts of sodium nitrite. Likewise was studied the influence of temperature on the decomposition of the above mentioned compounds. The activation energies of the studied reactions in acidic medium were 4.12 (n-nitrososarcosine), 19.3 (creatinine-5-oxime), and 20.2 kcal/mol (l-methylhydantoin-5-oxime), respectively.", "contents": "The nitrosation products of creatine and creatinine in model systems. The formation of N-nitrososarcosine from creatine, creatinine-5-oxime and l-methylhydantoin-5-oxime from creatinine was investigated in model solutions under various conditions (temperature, pH, concentration of sodium nitrite). N-nitrososarcosine was formed from creatine only in strongly acidic medium and its concentration increased with temperature and concentration of sodium nitrite. No N-nitrososarcosine was detected at 0 degrees C and in the presence of an equimolar amount of sodium nitrite. Creatinine-5-oxime and l-methylhydantoin-5-oxime was formed from creatinine in a broad region of pH, the highest concentration of these compounds was found in pH 3.6. The main reaction product was l-methylhydantoin-5-oxime. At a given pH, the concentrations of these two oximes increased generally with increased temperature and/or concentration of sodium nitrite. No oxime were detected at O degrees C and in the presence of equimolar amounts of sodium nitrite. Likewise was studied the influence of temperature on the decomposition of the above mentioned compounds. The activation energies of the studied reactions in acidic medium were 4.12 (n-nitrososarcosine), 19.3 (creatinine-5-oxime), and 20.2 kcal/mol (l-methylhydantoin-5-oxime), respectively."}
{"id": "PMID:7060", "title": "[Examinations to phenomenon of shock-lung (author's transl)].", "content": "The pathogenesis of shock lung as well as the success of therapy in this condition was studied in 79 cases of extrathoracic trauma. The water-, hemoglobin-, and DNA contents of the lungs were measured in order to determine the extent of edema, the rate of perfusion, and proliferation. The cases were divided into two groups according to whether they had or had not received medical therapy before death. The data from these two groups were compared using statistical methods in which time of survival was especially taken into account. The fluid balance, pO2, pCO2, central venous pressure, pH of the serum, total serum protein and serum creatinine were also studied in these cases. Results of the study are as follows. Three phases of the posttraumatic syndrome of shock-lung could be distinguished: phase I (initial phase): blood perfusion is increased, edema is beginning to form, and medical treatment has not yet begun. Phase II (early phase = sydrome of early respiratory failure): pulmonary edema is developing rapidly while perfusion is decreasing. Phase III (late phase = syndrome of late respiratory failure): proliferative changes predominante and the edema is still increasing. The mean weight of the lungs was 397 g (s = 170) in phase I, 774 G (S = 361) In phase II, and 1124 g (s = 310) in phase III. The survival times correlated significantly and positively with the amount of water and DNS in the lungs and significantly and negatively to the amount of hemoglobin in the lungs. Thus, increasing pulmonary edema and increasing proliferative changes occurred with decreasing pulmonary perfusion. This correlation was even noted in groups of patients who had not received medical treatment and whose survival times were short. In treated cases, the fluid balance was significantly and negatively correlated to the total serum protein.", "contents": "[Examinations to phenomenon of shock-lung (author's transl)]. The pathogenesis of shock lung as well as the success of therapy in this condition was studied in 79 cases of extrathoracic trauma. The water-, hemoglobin-, and DNA contents of the lungs were measured in order to determine the extent of edema, the rate of perfusion, and proliferation. The cases were divided into two groups according to whether they had or had not received medical therapy before death. The data from these two groups were compared using statistical methods in which time of survival was especially taken into account. The fluid balance, pO2, pCO2, central venous pressure, pH of the serum, total serum protein and serum creatinine were also studied in these cases. Results of the study are as follows. Three phases of the posttraumatic syndrome of shock-lung could be distinguished: phase I (initial phase): blood perfusion is increased, edema is beginning to form, and medical treatment has not yet begun. Phase II (early phase = sydrome of early respiratory failure): pulmonary edema is developing rapidly while perfusion is decreasing. Phase III (late phase = syndrome of late respiratory failure): proliferative changes predominante and the edema is still increasing. The mean weight of the lungs was 397 g (s = 170) in phase I, 774 G (S = 361) In phase II, and 1124 g (s = 310) in phase III. The survival times correlated significantly and positively with the amount of water and DNS in the lungs and significantly and negatively to the amount of hemoglobin in the lungs. Thus, increasing pulmonary edema and increasing proliferative changes occurred with decreasing pulmonary perfusion. This correlation was even noted in groups of patients who had not received medical treatment and whose survival times were short. In treated cases, the fluid balance was significantly and negatively correlated to the total serum protein."}
{"id": "PMID:7062", "title": "[Bacteriological findings in materials from patients with nonspecific odontogenic infections].", "content": "The results of bacteriological studies made between 1964 and 1971 by workers at the Varia Laboratory, Institute of Medical Microbiology on 767 patients treated at the Clinic of Gnathofacial Surgery, Department of Medicine, Friedrich Schiller University at Jena, are evaluated. The testees (x=275) were included in groups with specific diagnoses, and a breakdown was made according to the detection of aerobic pus-forming germs. Gram-positive cocci were detected in 92% of the cases and their pathogenetic representatives, 76,5% of the cases. Rodshaped germs (Enterobacteriaceae, Pseudomonas) were observed only in 37,9% of the cases. Staphylococcus aureus, which accounted for 62,5%, was the most frequently observed species. It was followed, in order of frequency of detection, by greening streptococci and Staphylococcus epidermidis. Monoinfection was far more frequently observed than multi-infection. Also, the problems associated with the differentiation of streptococci are pointed out since other investigators found streptococci to be the most frequent agents producing odontogenic infections.", "contents": "[Bacteriological findings in materials from patients with nonspecific odontogenic infections]. The results of bacteriological studies made between 1964 and 1971 by workers at the Varia Laboratory, Institute of Medical Microbiology on 767 patients treated at the Clinic of Gnathofacial Surgery, Department of Medicine, Friedrich Schiller University at Jena, are evaluated. The testees (x=275) were included in groups with specific diagnoses, and a breakdown was made according to the detection of aerobic pus-forming germs. Gram-positive cocci were detected in 92% of the cases and their pathogenetic representatives, 76,5% of the cases. Rodshaped germs (Enterobacteriaceae, Pseudomonas) were observed only in 37,9% of the cases. Staphylococcus aureus, which accounted for 62,5%, was the most frequently observed species. It was followed, in order of frequency of detection, by greening streptococci and Staphylococcus epidermidis. Monoinfection was far more frequently observed than multi-infection. Also, the problems associated with the differentiation of streptococci are pointed out since other investigators found streptococci to be the most frequent agents producing odontogenic infections."}
{"id": "PMID:7090", "title": "Alkaline phosphatase of Thiobacillus thioparus. Partial purification and properties of the enzyme.", "content": "Soluble alkaline phosphatase from Thiobacillus thioparus cells was purified about 230-fold. The enzyme had a mol. wt. of 50 000 daltons, optimum pH at 10.5, and was heat-resistant in the presence of diethanolamine. Polyacrylamide-gel electrophoresis demonstrated contamination of the preparation with inactive proteins and the presence of two active bands. The enzyme activity was distinctly stimulated by increasing concentrations of Tris or diethanolamine. In the presence of glycine, 1 mM-Zn2+ enhanced the enzyme activity; in Tris or diethanolamine buffers the activity was stimulated by 1 mM-Mg2+ whereas Zn2+ had a strong inhibitory effect. Glycine at concentrations exceeding 25 mM also inhibited the enzyme. Specificity of the enzyme is fairly broad.", "contents": "Alkaline phosphatase of Thiobacillus thioparus. Partial purification and properties of the enzyme. Soluble alkaline phosphatase from Thiobacillus thioparus cells was purified about 230-fold. The enzyme had a mol. wt. of 50 000 daltons, optimum pH at 10.5, and was heat-resistant in the presence of diethanolamine. Polyacrylamide-gel electrophoresis demonstrated contamination of the preparation with inactive proteins and the presence of two active bands. The enzyme activity was distinctly stimulated by increasing concentrations of Tris or diethanolamine. In the presence of glycine, 1 mM-Zn2+ enhanced the enzyme activity; in Tris or diethanolamine buffers the activity was stimulated by 1 mM-Mg2+ whereas Zn2+ had a strong inhibitory effect. Glycine at concentrations exceeding 25 mM also inhibited the enzyme. Specificity of the enzyme is fairly broad."}
{"id": "PMID:7091", "title": "Purification and properties of L-asparaginase from Mycobacterium phlei.", "content": "1. L-asparaginase from M. phlei was purified about 170-fold with an 11% yield. The purification procedure consisted of: fractionation with ammonium sulphate; adsorption of contaminating proteins on calcium phosphate gel; chromatography on Sephadex G-150 and DEAE-cellulose. The specific activity of the final preparation was 32.6 i.u./mg protein. 2. Molecular weight of the enzyme as determined by Sephadex G-100 filtration amounted to 126 000. Optimum pH was 8.8-9.2. The enzyme did not hydrolyse L-glutamine over the pH range 4-9, and was inhibited by D-asparagine. The apparent Michaelis constant for L-asparagine was 0.7 mM; energy of activation, 9800 cal/mole. 3. On polyacrylamide-gel electrophoresis the final preparation revealed two protein bands, one of which was coincident with the enzyme activity.", "contents": "Purification and properties of L-asparaginase from Mycobacterium phlei. 1. L-asparaginase from M. phlei was purified about 170-fold with an 11% yield. The purification procedure consisted of: fractionation with ammonium sulphate; adsorption of contaminating proteins on calcium phosphate gel; chromatography on Sephadex G-150 and DEAE-cellulose. The specific activity of the final preparation was 32.6 i.u./mg protein. 2. Molecular weight of the enzyme as determined by Sephadex G-100 filtration amounted to 126 000. Optimum pH was 8.8-9.2. The enzyme did not hydrolyse L-glutamine over the pH range 4-9, and was inhibited by D-asparagine. The apparent Michaelis constant for L-asparagine was 0.7 mM; energy of activation, 9800 cal/mole. 3. On polyacrylamide-gel electrophoresis the final preparation revealed two protein bands, one of which was coincident with the enzyme activity."}
{"id": "PMID:7092", "title": "The synthesis and properties of N6-substituted 2-amino-purine derivatives.", "content": "1. The synthesis, ultraviolet absorption spectra, and behaviour in alkali of N6-methoxy-, N6-methyl, hydroxy-, and N6-hydroxy-2-aminopurines have been described 2. N6-Methoxy-2-aminopurine riboside 5'-pyrophosphate has been prepared and used for polymerization with polynucleotide phosphorylase. 3. The copolymer containing N6-methoxy-2-aminopurine riboside and adenosine residues has been obtained; attempts to synthesize the homopolymer have not been successful. 4. All the purine analogues synthesized have been tested and shown to act mutagenically on Salmonella typhimurium TA1530.", "contents": "The synthesis and properties of N6-substituted 2-amino-purine derivatives. 1. The synthesis, ultraviolet absorption spectra, and behaviour in alkali of N6-methoxy-, N6-methyl, hydroxy-, and N6-hydroxy-2-aminopurines have been described 2. N6-Methoxy-2-aminopurine riboside 5'-pyrophosphate has been prepared and used for polymerization with polynucleotide phosphorylase. 3. The copolymer containing N6-methoxy-2-aminopurine riboside and adenosine residues has been obtained; attempts to synthesize the homopolymer have not been successful. 4. All the purine analogues synthesized have been tested and shown to act mutagenically on Salmonella typhimurium TA1530."}
{"id": "PMID:7093", "title": "Amnesic action of and skills related to driving after intravenous flunitrazepam.", "content": "Amnesic action, skills related to driving and the ability to discriminate the fusion of flickering light were measured double-blind in 29 healthy volunteers before and after three doses of intravenous flunitrazepam. Every subject experienced amnesia for the pinching of the abdomen after being injected with flunitrazepam. Even the smallest dose of flunitrazepam (0.01 mg/kg) caused the amnesia without affecting the level of consciousness. The late effects of flunitrazepam were the most harmful to coordination. With 0.01 mg/kg eye-hand coordination was slightly impaired for as long as 6 h after the injection, and after 0.02 and 0.03 mg/kg the impairment was still significant (P less than 0.05) at the last observation period 10 h after the injection. It was concluded that, because the amnesic action of flunitrazepam is more effective than that of clinically comparable doses of diazepam, further clinical experiments with flunitrazepam are warranted. Its longer and more harmful effects on psychomotor performance than those of equipotent doses of diazepam suggest that doses of 0.02 mg/kg or more of flunitrazepam should be avoided in outpatient anaesthesia or sedation.", "contents": "Amnesic action of and skills related to driving after intravenous flunitrazepam. Amnesic action, skills related to driving and the ability to discriminate the fusion of flickering light were measured double-blind in 29 healthy volunteers before and after three doses of intravenous flunitrazepam. Every subject experienced amnesia for the pinching of the abdomen after being injected with flunitrazepam. Even the smallest dose of flunitrazepam (0.01 mg/kg) caused the amnesia without affecting the level of consciousness. The late effects of flunitrazepam were the most harmful to coordination. With 0.01 mg/kg eye-hand coordination was slightly impaired for as long as 6 h after the injection, and after 0.02 and 0.03 mg/kg the impairment was still significant (P less than 0.05) at the last observation period 10 h after the injection. It was concluded that, because the amnesic action of flunitrazepam is more effective than that of clinically comparable doses of diazepam, further clinical experiments with flunitrazepam are warranted. Its longer and more harmful effects on psychomotor performance than those of equipotent doses of diazepam suggest that doses of 0.02 mg/kg or more of flunitrazepam should be avoided in outpatient anaesthesia or sedation."}
{"id": "PMID:7094", "title": "A comparison of the effects of the inhalation of 4% and 8% fluroxene in the pregnant primate.", "content": "A comparison was made of the effects of inhalation of 4% fluroxene (n = 5) and 8% fluroxene (n = 5) in pregnant monkeys. Measurements of maternal arterial blood pressure, heart rate, cardiac output, total peripheral resistance, uterine blood flow, fetal heart rate and arterial blood pressure, and maternal and fetal blood gas levels were made. Inhalation of 4% fluroxene for 20 minutes produced little change in maternal hemodynamics and was well tolerated by the fetus. Fluroxene 8% inhaled for a similar 20-minute-period produced a significant decrease in maternal blood pressure (--27%), total peripheral resistance (--32%), and uterine blood flow (--27%) and lowered the level of maternal fetal exchange.", "contents": "A comparison of the effects of the inhalation of 4% and 8% fluroxene in the pregnant primate. A comparison was made of the effects of inhalation of 4% fluroxene (n = 5) and 8% fluroxene (n = 5) in pregnant monkeys. Measurements of maternal arterial blood pressure, heart rate, cardiac output, total peripheral resistance, uterine blood flow, fetal heart rate and arterial blood pressure, and maternal and fetal blood gas levels were made. Inhalation of 4% fluroxene for 20 minutes produced little change in maternal hemodynamics and was well tolerated by the fetus. Fluroxene 8% inhaled for a similar 20-minute-period produced a significant decrease in maternal blood pressure (--27%), total peripheral resistance (--32%), and uterine blood flow (--27%) and lowered the level of maternal fetal exchange."}
{"id": "PMID:7095", "title": "Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial.", "content": "A double-blind controlled trial based on 140 women undergoing abortus provocatus was employed to study whether the frequency of side effects after administration of the anaesthetic Ketalar (ketamine) could be reduced by a con-current dose of Rohypnol (flunitrazepam). The control group was given ketamine alone. The dosage of ketamine was 2 mg/kg body weight, supplemented if necessary by 1 mg/kg, in combination with either 2 mg flunitrazepam or placebo. No other anaesthetics were used. On several counts, the combination of ketamine and flunitrazepam was proved to reduce the adverse reactions seen with ketamine alone. Motor restlessness and confusion in the awakening state occurred with significantly less severity and frequency. Amnesia for dreams was significantly more frequent. Memory of dreams was often unpleasant after ketamine alone. The influence on pulse rate was significantly smaller and no significant changes in systolic blood pressure were seen, whereas a significant increase occurred with ketamine alone. Less pronounced fluctuations in diastolic blood pressure occurred with the combination ketamine-flunitrazepam. Respiratory rate increased significantly with both treatments, but respiratory minute volume was lower with the ketamine-flunitrazepam combination.", "contents": "Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial. A double-blind controlled trial based on 140 women undergoing abortus provocatus was employed to study whether the frequency of side effects after administration of the anaesthetic Ketalar (ketamine) could be reduced by a con-current dose of Rohypnol (flunitrazepam). The control group was given ketamine alone. The dosage of ketamine was 2 mg/kg body weight, supplemented if necessary by 1 mg/kg, in combination with either 2 mg flunitrazepam or placebo. No other anaesthetics were used. On several counts, the combination of ketamine and flunitrazepam was proved to reduce the adverse reactions seen with ketamine alone. Motor restlessness and confusion in the awakening state occurred with significantly less severity and frequency. Amnesia for dreams was significantly more frequent. Memory of dreams was often unpleasant after ketamine alone. The influence on pulse rate was significantly smaller and no significant changes in systolic blood pressure were seen, whereas a significant increase occurred with ketamine alone. Less pronounced fluctuations in diastolic blood pressure occurred with the combination ketamine-flunitrazepam. Respiratory rate increased significantly with both treatments, but respiratory minute volume was lower with the ketamine-flunitrazepam combination."}
{"id": "PMID:7097", "title": "The experiment on the protein exposed to acoustic wave in model of hair cells.", "content": "Why do animals have intense troubles mainly in the basal turns of their cochleae by exposure to sound and the ototoxity? I thought that the protein in cells had an important relation to this subject. So I performed this experiment. I made model of hair cells of silicon and poured three kinds of solutions of protein into them. And I checked the ionization of the protein and its denaturation by giving strong energy of oscillation to them like the same idea of photoelectric effect. As the result, as for the protein liquid, I noticed the increase of volts just after it was exposed to sound and about 3 hours later, I observed the figure decreased gradually. From this phenomenon, I presumed that the protein in sensory cells became a factor of the stimulation by receiving strong energy conversely. Low-percent protein liquid had less effect caused by sound.", "contents": "The experiment on the protein exposed to acoustic wave in model of hair cells. Why do animals have intense troubles mainly in the basal turns of their cochleae by exposure to sound and the ototoxity? I thought that the protein in cells had an important relation to this subject. So I performed this experiment. I made model of hair cells of silicon and poured three kinds of solutions of protein into them. And I checked the ionization of the protein and its denaturation by giving strong energy of oscillation to them like the same idea of photoelectric effect. As the result, as for the protein liquid, I noticed the increase of volts just after it was exposed to sound and about 3 hours later, I observed the figure decreased gradually. From this phenomenon, I presumed that the protein in sensory cells became a factor of the stimulation by receiving strong energy conversely. Low-percent protein liquid had less effect caused by sound."}
{"id": "PMID:7100", "title": "Effects of metoprolol in angina pectoris. A subacute study with exercise tests and a long-term tolerability study.", "content": "Eighteen patients with angina pectoris, who had previously participated in a cross-over study with 20 mg metoprolol t.i.d. and placebo, have been included in this study. During an introductory six-month open tolerability study, all patients were treated with 50 mg metoprolol t.i.d. and during a subsequent cross-over study, the efficacy of this dose was compared with that of placebo under double-blind conditions. An exercise was performed at the end of each cross-over period. Metoprolol, in a dose of 50 mg t.i.d., gave a significant improvement compared with placebo in respect of the number of anginal attacks, nitroglycerin consumption and daily subjective assessment of the patients' anginal symptoms. Metoprolol also gave a significant increase in exercise capacity, both until the appearance of 1 mm ST segment depression and until the end of exercise. Heart rate and blood pressure were reduced both at rest and during exercise. No severe unwanted effects were observed during this study ranging over eight months, and none of the patients had any signs or symptoms of cardiac failure or pulmonary dysfunction on any occasion. Unwanted effects reported were mild to moderate, and the frequency was the same as during placebo treatment. No abnormal laboratory findings were observed and the relative heart volume was not significantly changed. Administration of 50 mg metoprolol t.i.d. seems to be of greater benefit than 20 mg metoprolol t.i.d., previously investigated in these patients.", "contents": "Effects of metoprolol in angina pectoris. A subacute study with exercise tests and a long-term tolerability study. Eighteen patients with angina pectoris, who had previously participated in a cross-over study with 20 mg metoprolol t.i.d. and placebo, have been included in this study. During an introductory six-month open tolerability study, all patients were treated with 50 mg metoprolol t.i.d. and during a subsequent cross-over study, the efficacy of this dose was compared with that of placebo under double-blind conditions. An exercise was performed at the end of each cross-over period. Metoprolol, in a dose of 50 mg t.i.d., gave a significant improvement compared with placebo in respect of the number of anginal attacks, nitroglycerin consumption and daily subjective assessment of the patients' anginal symptoms. Metoprolol also gave a significant increase in exercise capacity, both until the appearance of 1 mm ST segment depression and until the end of exercise. Heart rate and blood pressure were reduced both at rest and during exercise. No severe unwanted effects were observed during this study ranging over eight months, and none of the patients had any signs or symptoms of cardiac failure or pulmonary dysfunction on any occasion. Unwanted effects reported were mild to moderate, and the frequency was the same as during placebo treatment. No abnormal laboratory findings were observed and the relative heart volume was not significantly changed. Administration of 50 mg metoprolol t.i.d. seems to be of greater benefit than 20 mg metoprolol t.i.d., previously investigated in these patients."}
{"id": "PMID:7101", "title": "Effect of sugars, hydrogen ion concentration and ammonium nitrate on the formation of citric acid by Aspergillus niger.", "content": "Aspergillus niger Mulder strain when grown on a synthetic medium containing urea as the sole source of nitrogen at pH 5.2, formed a mixture of citric and gluconic acids. On growing the organism at pH 2.0 the gluconic acid content was reduced but citric acid yield remained low. Addition of NH4NO3 to the medium lowered the gluconic acid yields to undetectable levels with a simultaneous increase in the citric acid content. Of the sugars used for the production of citric acid, sucrose in an unautoclaved medium was found to be the best carbon source. Sucrose medium if autoclaved at pH 2.0, or a mixture of glucose and fructose instead of sucrose gave lower yields of citric acid. Under optimum conditions only citric acid was produced and the yield was 66-68 per litre after a growth period of about 10 days.", "contents": "Effect of sugars, hydrogen ion concentration and ammonium nitrate on the formation of citric acid by Aspergillus niger. Aspergillus niger Mulder strain when grown on a synthetic medium containing urea as the sole source of nitrogen at pH 5.2, formed a mixture of citric and gluconic acids. On growing the organism at pH 2.0 the gluconic acid content was reduced but citric acid yield remained low. Addition of NH4NO3 to the medium lowered the gluconic acid yields to undetectable levels with a simultaneous increase in the citric acid content. Of the sugars used for the production of citric acid, sucrose in an unautoclaved medium was found to be the best carbon source. Sucrose medium if autoclaved at pH 2.0, or a mixture of glucose and fructose instead of sucrose gave lower yields of citric acid. Under optimum conditions only citric acid was produced and the yield was 66-68 per litre after a growth period of about 10 days."}
{"id": "PMID:7105", "title": "Arylsulfatases A and B in metachromatic leukodystrophy and Maroteaux-Lamy syndrome: studies with 4-methylumelliferyl sulfate.", "content": "Metachromatic leukodystrophy and Maroteaux-Lamy syndrome can be diagnosed by assay of leukocyte or fibroblast arylsulfatase A and B activity with the fluorogenic substrate 4-methylumbelliferyl sulfate. The arylsulfatases are extracted into a 27000 x g supernatant by sonication in 0.9% sodium chloride and then separated with CM-32 on columns or in test tubes. In 0.05 M sodium acetate pH 6.0, arylsulfatase A is not absorbed while arylsulfatase B is retained by the resin. The arylsulfatase B is then eluted from the resin with 0.3 M sodium chloride. The arylsulfatase A activity obtained from normal leukocytes and fibroblasts is linear for the initial 10 minutes of the reaction, is stimulated 3-fold by 6 mM lead acetate and inhibited 80% by 0.24 mM silver nitrate. After separation with CM-32, the arylsulfatase B activity is stimulated 3-fold by Triton X-100 (0.1%). Arylsulfatase A but not arylsulfatase B is destroyed by heat (60 degrees). Both leukocyte and fibroblast arylsulfatase A activity was reduced to 11% of control values in metachromatic leukodystrophy. Essentially no arylsulfatase B activity was detected in cells from patients with Maroteaux-Lamy syndrome. Metachromatic leukodystrophy heterozygotes but not Maroteaux-Lamy syndrome heterozygotes can also be distinguished by this method. A heat inactivation technique utilizing the differential thermal stabilities of the two enzymes for diagnosis of patients with Marotezux-Lamy syndrome is also described. The advantages of these 4-methylumbelliferyl sulfate assay procedures over the p-nitrocatechol sulfate method of assay are greater sensitivity, selectivity for the desired enzyme and potential for use in large scale testing.", "contents": "Arylsulfatases A and B in metachromatic leukodystrophy and Maroteaux-Lamy syndrome: studies with 4-methylumelliferyl sulfate. Metachromatic leukodystrophy and Maroteaux-Lamy syndrome can be diagnosed by assay of leukocyte or fibroblast arylsulfatase A and B activity with the fluorogenic substrate 4-methylumbelliferyl sulfate. The arylsulfatases are extracted into a 27000 x g supernatant by sonication in 0.9% sodium chloride and then separated with CM-32 on columns or in test tubes. In 0.05 M sodium acetate pH 6.0, arylsulfatase A is not absorbed while arylsulfatase B is retained by the resin. The arylsulfatase B is then eluted from the resin with 0.3 M sodium chloride. The arylsulfatase A activity obtained from normal leukocytes and fibroblasts is linear for the initial 10 minutes of the reaction, is stimulated 3-fold by 6 mM lead acetate and inhibited 80% by 0.24 mM silver nitrate. After separation with CM-32, the arylsulfatase B activity is stimulated 3-fold by Triton X-100 (0.1%). Arylsulfatase A but not arylsulfatase B is destroyed by heat (60 degrees). Both leukocyte and fibroblast arylsulfatase A activity was reduced to 11% of control values in metachromatic leukodystrophy. Essentially no arylsulfatase B activity was detected in cells from patients with Maroteaux-Lamy syndrome. Metachromatic leukodystrophy heterozygotes but not Maroteaux-Lamy syndrome heterozygotes can also be distinguished by this method. A heat inactivation technique utilizing the differential thermal stabilities of the two enzymes for diagnosis of patients with Marotezux-Lamy syndrome is also described. The advantages of these 4-methylumbelliferyl sulfate assay procedures over the p-nitrocatechol sulfate method of assay are greater sensitivity, selectivity for the desired enzyme and potential for use in large scale testing."}
{"id": "PMID:7107", "title": "Identification of Tay-Sachs by hexosaminidase analysis of urine and tear samples.", "content": "1. Two readily obtainable biological fluids, i.e., urine and tears, were investigated as possible substitutes for serum and leukocytes for the detection of Tay-Sachs disease (TSD) heterozygotes based on Quantitative hexosaminidase A (Hex A) determinations. 2. Hexosaminidase isoenzyme patterns were determined, by means of an automated DEAE-cellulose microcolumn procedure, for serum, urine and tear samples from normals, TSD carriers, normal pregnancies, carrier-pregnancies and TSD children. 3. Normal pregnancy and TSD carrier sera gave almost identical hexosaminidase patterns with multiple intermediate peaks. Whereas, urine and tear samples from normal pregnant women showed hexosaminidase isoenzyme patterns resembling those of normal controls. These results suggested that use of these fluids might eliminate the effect of pregnancy of the Hex A ratio which occurs when serum is used as the test fluid. In addition these fluids are most economical and simpler to obtain than a blood sample. 4. About 200 urine samples, from the various categories listed above, were analyzed for Hex A with both the heat denaturation and pH inactivation methods and the results compared with serum and leukocyte levels from many of the same individuals. With either method, the wide overlap between the urinary Hex A normal and heterozygote ranges would require retesting with leukocytes of about 30% of the subjects. These results would preclude the use of urines as a suitable fluid for the mass screening of the Ashkenazic Jewish population for TSD heterozygotes.", "contents": "Identification of Tay-Sachs by hexosaminidase analysis of urine and tear samples. 1. Two readily obtainable biological fluids, i.e., urine and tears, were investigated as possible substitutes for serum and leukocytes for the detection of Tay-Sachs disease (TSD) heterozygotes based on Quantitative hexosaminidase A (Hex A) determinations. 2. Hexosaminidase isoenzyme patterns were determined, by means of an automated DEAE-cellulose microcolumn procedure, for serum, urine and tear samples from normals, TSD carriers, normal pregnancies, carrier-pregnancies and TSD children. 3. Normal pregnancy and TSD carrier sera gave almost identical hexosaminidase patterns with multiple intermediate peaks. Whereas, urine and tear samples from normal pregnant women showed hexosaminidase isoenzyme patterns resembling those of normal controls. These results suggested that use of these fluids might eliminate the effect of pregnancy of the Hex A ratio which occurs when serum is used as the test fluid. In addition these fluids are most economical and simpler to obtain than a blood sample. 4. About 200 urine samples, from the various categories listed above, were analyzed for Hex A with both the heat denaturation and pH inactivation methods and the results compared with serum and leukocyte levels from many of the same individuals. With either method, the wide overlap between the urinary Hex A normal and heterozygote ranges would require retesting with leukocytes of about 30% of the subjects. These results would preclude the use of urines as a suitable fluid for the mass screening of the Ashkenazic Jewish population for TSD heterozygotes."}
{"id": "PMID:7111", "title": "[Contribution to the knowledge of Swiss piroplasmas].", "content": "The authors identify 3 species of Babesia, which parasitize cattle in Switzerland (Babesia major, B. divergens and B. hovis). They also confirm the presence of B. canis in a dog in the proximity of Geneva. Finally, for the first time in Switzerland, they point out the presence of non-identified Babesia in various rodents (Apodemus sylvaticus, A. flavicollis and Clethrionomys glareolus).", "contents": "[Contribution to the knowledge of Swiss piroplasmas]. The authors identify 3 species of Babesia, which parasitize cattle in Switzerland (Babesia major, B. divergens and B. hovis). They also confirm the presence of B. canis in a dog in the proximity of Geneva. Finally, for the first time in Switzerland, they point out the presence of non-identified Babesia in various rodents (Apodemus sylvaticus, A. flavicollis and Clethrionomys glareolus)."}
{"id": "PMID:7112", "title": "[Apropos of the asexual multiplication of the tetrathyridia larva of Mesocestoides corti Hoeppli, 1925 (Cestoda: cyclophyllidea). (Prelimary note )].", "content": "In Tetrathyridia of Mesocestoides corti exist large basophilic cells which are often seen in various stages of mitosis. From their distribution in larvae and from their capacity to form the regeneration blastema after experimental amputation of 2 suckers, it is supposed that these cells are very important for regeneration.", "contents": "[Apropos of the asexual multiplication of the tetrathyridia larva of Mesocestoides corti Hoeppli, 1925 (Cestoda: cyclophyllidea). (Prelimary note )]. In Tetrathyridia of Mesocestoides corti exist large basophilic cells which are often seen in various stages of mitosis. From their distribution in larvae and from their capacity to form the regeneration blastema after experimental amputation of 2 suckers, it is supposed that these cells are very important for regeneration."}
{"id": "PMID:7113", "title": "[The biological cycle of Caryophyllaeus brachycollis Janiszweska, 1953 (Cestoda carophyllaeidae) a parasite of Barbus meridionalis Risso, 1826 in the south of France].", "content": "Caryophyllaeus brachycollis Janiszweska, 1953 has been found for the first time in France in Barbus meridionalis Risso, 1926. Experimentally, the procercoid develops in Tubifex sp. and never in Limnodrilus sp. The different possibilities of life cycle of C. brachycollis in Europe have been compared.", "contents": "[The biological cycle of Caryophyllaeus brachycollis Janiszweska, 1953 (Cestoda carophyllaeidae) a parasite of Barbus meridionalis Risso, 1826 in the south of France]. Caryophyllaeus brachycollis Janiszweska, 1953 has been found for the first time in France in Barbus meridionalis Risso, 1926. Experimentally, the procercoid develops in Tubifex sp. and never in Limnodrilus sp. The different possibilities of life cycle of C. brachycollis in Europe have been compared."}
{"id": "PMID:7114", "title": "[Rats and bilharziasis in Guadeloupe].", "content": "The rats in Guadeloupe (Rattus rattus and Rattus norvegicus) may play a  part in schistosomiasis in three ways: - by harbouring fertile S. mansoni, a fact which serves to increase the total population of the parasite and may eventually take part in the infestation of man; - by harbouring a great number of Ribeiroia marini, a trematode whose larval stages sterilize Biomphalaria glabrata, the vector of schistosomiasis; - simply by eating B. glabrata. The quantitative influence of these contradictory roles played by the rats upon schistosomiasis in Guadeloupe has yet to be studied.", "contents": "[Rats and bilharziasis in Guadeloupe]. The rats in Guadeloupe (Rattus rattus and Rattus norvegicus) may play a  part in schistosomiasis in three ways: - by harbouring fertile S. mansoni, a fact which serves to increase the total population of the parasite and may eventually take part in the infestation of man; - by harbouring a great number of Ribeiroia marini, a trematode whose larval stages sterilize Biomphalaria glabrata, the vector of schistosomiasis; - simply by eating B. glabrata. The quantitative influence of these contradictory roles played by the rats upon schistosomiasis in Guadeloupe has yet to be studied."}
{"id": "PMID:7115", "title": "[The chronobiology of the cercaria of Ribeiroia marini (Faust and Hoffman, 1934) parasite of Biomphalaria glabrata: effect of the photoperiod on the rhythm of emergence].", "content": "Ribeiroir marini cercariage emerge from the snail-host during the night, according to a circadian rhythm. The photoperiod is the synchronizer of this rhythm. Inversion of the photoperiod is immediately followed by inversion of the periodicity of emergence. No cercaria emerge in continuous light conditions. This inhibitory effect of light exerts its influence on the emergence but not on the production of cercariae. The rhythmic emergence is almost maintained in continous dark, but darkness cannot induce emergence at any time. It is possible that an innate production rhythm interferes with the emergence rhythm.", "contents": "[The chronobiology of the cercaria of Ribeiroia marini (Faust and Hoffman, 1934) parasite of Biomphalaria glabrata: effect of the photoperiod on the rhythm of emergence]. Ribeiroir marini cercariage emerge from the snail-host during the night, according to a circadian rhythm. The photoperiod is the synchronizer of this rhythm. Inversion of the photoperiod is immediately followed by inversion of the periodicity of emergence. No cercaria emerge in continuous light conditions. This inhibitory effect of light exerts its influence on the emergence but not on the production of cercariae. The rhythmic emergence is almost maintained in continous dark, but darkness cannot induce emergence at any time. It is possible that an innate production rhythm interferes with the emergence rhythm."}
{"id": "PMID:7116", "title": "[Contribution to the study of Microphallidae Travassos 1920 (trematoda). XXXII. Microphallus breviatus n. sp., a species with an abbreviated evolutive cycle from a Mediterranean pond in the Languedoc].", "content": "Contribution to the study of Microphallidae Travassos, 1920 (Trematoda). XXXII. - Microphallus breviatus n. sp., a short life-cycle species of a mediterranean pond of Languedoc. The whole larval life-cycle of M. breviatus takes place in one host, Hydrobia ventrosa (Montagu), Mollusc Hydrobiidae. Hepato-pancreatic sporocysts produce morphologically altered xiphidio-cercariae which become encysted metacercariae in the sporocyts themselves. This species is defined in the genus by the anatomic characteristics of its cercariae and metacercariae, allied with its uncommon biology including two hosts only.", "contents": "[Contribution to the study of Microphallidae Travassos 1920 (trematoda). XXXII. Microphallus breviatus n. sp., a species with an abbreviated evolutive cycle from a Mediterranean pond in the Languedoc]. Contribution to the study of Microphallidae Travassos, 1920 (Trematoda). XXXII. - Microphallus breviatus n. sp., a short life-cycle species of a mediterranean pond of Languedoc. The whole larval life-cycle of M. breviatus takes place in one host, Hydrobia ventrosa (Montagu), Mollusc Hydrobiidae. Hepato-pancreatic sporocysts produce morphologically altered xiphidio-cercariae which become encysted metacercariae in the sporocyts themselves. This species is defined in the genus by the anatomic characteristics of its cercariae and metacercariae, allied with its uncommon biology including two hosts only."}
{"id": "PMID:7117", "title": "[Evolutive cycle of Paratimonia gobii, Prevot and Bartoli 1967 (trematoda-monorchiidea)].", "content": "The cycle of Paratimonia gobii PREVOT & BARTOLLI, 1967 (Trematoda-Monorchiidae), a parasite of Pomatoschistus microps (Teleostei gobiidae), has been discovered and carried out experimentally. The mollusc, first intermediary host,  is Abra ovata (Lamellibranchiata, Scrobiculariidae). The gymnocephalous cercaria leaves the mollusc, then sucked in by the respiratory stream, becomes encysted in the inhaling siphon of another Abra. The accumulation of metacercaria results in the autonomy of this siphon and it is this cut-off organ which is becoming part of the alimentary chain of the final host allows the continuation of the cycle.", "contents": "[Evolutive cycle of Paratimonia gobii, Prevot and Bartoli 1967 (trematoda-monorchiidea)]. The cycle of Paratimonia gobii PREVOT & BARTOLLI, 1967 (Trematoda-Monorchiidae), a parasite of Pomatoschistus microps (Teleostei gobiidae), has been discovered and carried out experimentally. The mollusc, first intermediary host,  is Abra ovata (Lamellibranchiata, Scrobiculariidae). The gymnocephalous cercaria leaves the mollusc, then sucked in by the respiratory stream, becomes encysted in the inhaling siphon of another Abra. The accumulation of metacercaria results in the autonomy of this siphon and it is this cut-off organ which is becoming part of the alimentary chain of the final host allows the continuation of the cycle."}
{"id": "PMID:7118", "title": "[A new nematode (allantonematidae) parasite of Heliophilus (T diptera, syrphidae)].", "content": "For the second time, the authors have found a new entomophagous nematode parasitic in Syrphidae. The first species, which was described as Syrphonematidae nov. fam., is living in the duct of various aphidophagous species of Syrphidae. This one has been found in the hemocoel of adults of Helophilus trivittatus Fabricius and H. pendulus Linneaus (Eristalinae with aquatic rat tailed larvae). It seems to belong to the genus Iotonchium (Allantonematidae), which was known as yet only by the free-living stages. This work could bring the proof that the genus Iotonchium is really parasite of insect as it was supposed by T. GOODEY and J. B. GOODEY. The three distinct forms which are living in the body cavity of the host are briefly described. The life cycle, which differs from those of all other Allantonematidae, is discussed. This species requires further studies, especially on the free-living stages which have to be obtained for the comparative study of the morphology of the various forms and for life history.", "contents": "[A new nematode (allantonematidae) parasite of Heliophilus (T diptera, syrphidae)]. For the second time, the authors have found a new entomophagous nematode parasitic in Syrphidae. The first species, which was described as Syrphonematidae nov. fam., is living in the duct of various aphidophagous species of Syrphidae. This one has been found in the hemocoel of adults of Helophilus trivittatus Fabricius and H. pendulus Linneaus (Eristalinae with aquatic rat tailed larvae). It seems to belong to the genus Iotonchium (Allantonematidae), which was known as yet only by the free-living stages. This work could bring the proof that the genus Iotonchium is really parasite of insect as it was supposed by T. GOODEY and J. B. GOODEY. The three distinct forms which are living in the body cavity of the host are briefly described. The life cycle, which differs from those of all other Allantonematidae, is discussed. This species requires further studies, especially on the free-living stages which have to be obtained for the comparative study of the morphology of the various forms and for life history."}
{"id": "PMID:7119", "title": "[Vegetation analysis used for the detection of exophile tick populations in the south-east of France: the example Ixodes ricinus (Linne 1758) (acarina, ixodoidea)].", "content": "The cross-linking relation between the evidence of outside living tick populations and specific vegetation units allows for efficiently using the vegetation maps, and more especially the medium scale maps. Ixodes ricinus is referred to here as an example. The limitations of this data derived from such maps are evaluated by the authors. They suggest some means aiding in improving their efficiency through the knowledge of the ecological variables playing a role in the species settlement.", "contents": "[Vegetation analysis used for the detection of exophile tick populations in the south-east of France: the example Ixodes ricinus (Linne 1758) (acarina, ixodoidea)]. The cross-linking relation between the evidence of outside living tick populations and specific vegetation units allows for efficiently using the vegetation maps, and more especially the medium scale maps. Ixodes ricinus is referred to here as an example. The limitations of this data derived from such maps are evaluated by the authors. They suggest some means aiding in improving their efficiency through the knowledge of the ecological variables playing a role in the species settlement."}
{"id": "PMID:7121", "title": "[An abnormally formed Ctenophthalmus assimilis assimilis (siphonapteres hystrichosyllidae)].", "content": "A female flea is described the body of which is abnormally formed and compressed. It is characterized by a split along its back, raised up abdominal segments and by a shortening of its head. These anomalies might be explained by longitudinal compression of the body during pupation. The possibility of a mutation is not excluded.", "contents": "[An abnormally formed Ctenophthalmus assimilis assimilis (siphonapteres hystrichosyllidae)]. A female flea is described the body of which is abnormally formed and compressed. It is characterized by a split along its back, raised up abdominal segments and by a shortening of its head. These anomalies might be explained by longitudinal compression of the body during pupation. The possibility of a mutation is not excluded."}
{"id": "PMID:7122", "title": "Advantages of x-ray microanalysis in the field of medical mycology.", "content": "A new apparatus, which combines an electron microprobe and a scanning electron microscope, has been used. This apparatus enabled to conduct a systematic elemental analysis of two species among Aspergillaceae. All elements in the periodic table whose atomic numbers lie between boron and uranium can be detected.", "contents": "Advantages of x-ray microanalysis in the field of medical mycology. A new apparatus, which combines an electron microprobe and a scanning electron microscope, has been used. This apparatus enabled to conduct a systematic elemental analysis of two species among Aspergillaceae. All elements in the periodic table whose atomic numbers lie between boron and uranium can be detected."}
{"id": "PMID:7123", "title": "[Hepatic amebiasis in the Kilimanjaro region. Serodiagnosis on micro-specimens of dried blood and attempts at treatment with tinidazole (fasigyn)].", "content": "Amoebic dysentery appears to be rare in the northeast of Tanzania. Hepatic amoebiasis, on the other hand, is apparently widespread since at least 200 cases are seen every year at the Kilimanjaro Christian Medical Centre. This incidence of cases enabled us to carry out trials on the spot with a new imidazole derivative, Tinidazole. Formerly the difficult diagnosis based on clinical symptoms had to be buttressed by radiological evidence and possibly by the result of puncture. Indirect fluorescent antibody tests for the diagnosis of amoebiasis were performed elsewhere on all the patients, using for this purpose microspecimens of dried blood. In 12 cases out of 34 an agglutination test with sensitized latex particles was performed on the spot. This latter test has the practical advantage of being easy to employ. It cannot, however, be considered as a screening test since it is subject to downward and upward errors. The indirect fluorescent antibody test has been found to be constantly and highly positive, certain antibody titres attaining 1/6400. This fully confirms the value of the method even under special working conditions. Seventeen of our 34 patients (2 women and 15 men ranging in age from 20 to 75 years) were treated with 2 g of Tinidazole per day in a single dose for 2 to 3 consecutive days. Puncture to evacuate pus was also performed where abscesses had collected. Tolerance on the whole was good without a single sign of cardiovascular or urinary toxicity. However, paraesthesia of the hands was observed in one case, transitory thrombocytopenia in one other patient, and increased alkaline phosphatases. Minor disorders were also observed in our series of patients: mild vertigo (7 cases), headache (6 cases), and dry mouth (2 cases). After 8 months the therapeutic results were as follows: 12 complete cures out of 17, 2 improvements with final cure probable, 3 partial failures necessitating supplementary treatment with Metronidazole (2.4 g per day for 2 days). These preliminary trials appear to the encouraging and the study is being continued with series compared with cases treated with Emetine or Metronidazole.", "contents": "[Hepatic amebiasis in the Kilimanjaro region. Serodiagnosis on micro-specimens of dried blood and attempts at treatment with tinidazole (fasigyn)]. Amoebic dysentery appears to be rare in the northeast of Tanzania. Hepatic amoebiasis, on the other hand, is apparently widespread since at least 200 cases are seen every year at the Kilimanjaro Christian Medical Centre. This incidence of cases enabled us to carry out trials on the spot with a new imidazole derivative, Tinidazole. Formerly the difficult diagnosis based on clinical symptoms had to be buttressed by radiological evidence and possibly by the result of puncture. Indirect fluorescent antibody tests for the diagnosis of amoebiasis were performed elsewhere on all the patients, using for this purpose microspecimens of dried blood. In 12 cases out of 34 an agglutination test with sensitized latex particles was performed on the spot. This latter test has the practical advantage of being easy to employ. It cannot, however, be considered as a screening test since it is subject to downward and upward errors. The indirect fluorescent antibody test has been found to be constantly and highly positive, certain antibody titres attaining 1/6400. This fully confirms the value of the method even under special working conditions. Seventeen of our 34 patients (2 women and 15 men ranging in age from 20 to 75 years) were treated with 2 g of Tinidazole per day in a single dose for 2 to 3 consecutive days. Puncture to evacuate pus was also performed where abscesses had collected. Tolerance on the whole was good without a single sign of cardiovascular or urinary toxicity. However, paraesthesia of the hands was observed in one case, transitory thrombocytopenia in one other patient, and increased alkaline phosphatases. Minor disorders were also observed in our series of patients: mild vertigo (7 cases), headache (6 cases), and dry mouth (2 cases). After 8 months the therapeutic results were as follows: 12 complete cures out of 17, 2 improvements with final cure probable, 3 partial failures necessitating supplementary treatment with Metronidazole (2.4 g per day for 2 days). These preliminary trials appear to the encouraging and the study is being continued with series compared with cases treated with Emetine or Metronidazole."}
{"id": "PMID:7124", "title": "[Epidemic of autochthonous hepatic and intestinal amebiasis in a place near Grenoble].", "content": "We had the opportunity of studying an epidemic of autochthonous amoebiasis occurring in the autumn of 1974 in a small town of 4000 inhabitants 30 km from Grenoble. Attention was originally attracted by the occurrence in this town of two cases of hepatic amoebiasis and one of intestinal amoebiasis identified by rectoscopy. Systematic investigations (coproctic examinations and serological tests for amoebiasis by indirect antibody fluorescence) were then carried out on everyone in the locality with digestive disorders which were possibly referable to amoebiasis, and on the other members of their families. A total number of 148 coproctic examinations were made and in two cases revealed the presence of vegetative forms of Entamoeba histolytica. In both cases the infestation provoked few symptoms (asthenia, vague abdominal discomfort, intermittent and apparently banal diarrhoea). On the other hand 20 out of 94 serological tests revealed positive results, 14 of which were equal to or greater than a titre of 1/100, a level at which all risks of non-specificity are virtually ruled out under our experimental conditions. Material reasons made it impossible to subject these cases to repeated faecal checks, but in two of them at least the rectoscopic appearances were very suggestive of subacute intestinal amoebiasis. Moreover, amoebic disease appears to be well confirmed by the results obtained among the patients as a whole by treatment with Metroinidazole. A variety of hypotheses on the origin of this epidemic have been put forward and then abandoned (market garden produce, receipt by certain families of exotic frut from overseas). In actual fact water seems to be the point of departure, for, although specimens of water taken at 7 different levels in the water supply system failed to reveal the presence of a single amoeba, bacteriological analyses during autumn 1974 showed signs of faecal contamination. The locality, which is situated at the foot of the Chartreuse massif, receives its water solely from springs but there is a holiday camp for the staff of an international airline situated above the main water catchment.", "contents": "[Epidemic of autochthonous hepatic and intestinal amebiasis in a place near Grenoble]. We had the opportunity of studying an epidemic of autochthonous amoebiasis occurring in the autumn of 1974 in a small town of 4000 inhabitants 30 km from Grenoble. Attention was originally attracted by the occurrence in this town of two cases of hepatic amoebiasis and one of intestinal amoebiasis identified by rectoscopy. Systematic investigations (coproctic examinations and serological tests for amoebiasis by indirect antibody fluorescence) were then carried out on everyone in the locality with digestive disorders which were possibly referable to amoebiasis, and on the other members of their families. A total number of 148 coproctic examinations were made and in two cases revealed the presence of vegetative forms of Entamoeba histolytica. In both cases the infestation provoked few symptoms (asthenia, vague abdominal discomfort, intermittent and apparently banal diarrhoea). On the other hand 20 out of 94 serological tests revealed positive results, 14 of which were equal to or greater than a titre of 1/100, a level at which all risks of non-specificity are virtually ruled out under our experimental conditions. Material reasons made it impossible to subject these cases to repeated faecal checks, but in two of them at least the rectoscopic appearances were very suggestive of subacute intestinal amoebiasis. Moreover, amoebic disease appears to be well confirmed by the results obtained among the patients as a whole by treatment with Metroinidazole. A variety of hypotheses on the origin of this epidemic have been put forward and then abandoned (market garden produce, receipt by certain families of exotic frut from overseas). In actual fact water seems to be the point of departure, for, although specimens of water taken at 7 different levels in the water supply system failed to reveal the presence of a single amoeba, bacteriological analyses during autumn 1974 showed signs of faecal contamination. The locality, which is situated at the foot of the Chartreuse massif, receives its water solely from springs but there is a holiday camp for the staff of an international airline situated above the main water catchment."}
{"id": "PMID:7125", "title": "[Leishmaniasis in south-eastern France- -ecology, epidemiology, prophylaxis].", "content": "A study of the ecology, epidemiology and prophylaxis of Leishmaniasis in the southeast of France is reported; different methods of the survey are recorded. Between 1965 and 1975, 972 cases of canine Leishmaniasis and from 1968 to 1975 89 cases of visceral human Leishmaniasis and only 3 cases of oriental sore were observed in the \"Bouches du Rh\u00f4ne\", \"Var\" and \"Vaucluse\" Departments. The strains isolated from canine and human visceral Leishmaniasis had a malate dehydrogenase XI whereas Leishmania tropica had a MDH I; no wild animals have been found with Leishmaniasis.  The suburbs of the towns, the hills in the center of Marseilles or surrounding Toulon as well as the villages are the principal foci of Phlebotomus perniciousus (96%) as the vector. The biotopes are isolated houses with little gardens surrounded by dry-stone walls exhibiting holes named \"barbacanes\", with chalky soil and xerophytes. The killing of infected dogs is the best protection of men whereas keeping dogs in sandfly-proof kennels from twilight until one hour after sunrise is best in order to protect this animal. This is quite different from the observations made by RIOUX in the Cevennes.", "contents": "[Leishmaniasis in south-eastern France- -ecology, epidemiology, prophylaxis]. A study of the ecology, epidemiology and prophylaxis of Leishmaniasis in the southeast of France is reported; different methods of the survey are recorded. Between 1965 and 1975, 972 cases of canine Leishmaniasis and from 1968 to 1975 89 cases of visceral human Leishmaniasis and only 3 cases of oriental sore were observed in the \"Bouches du Rh\u00f4ne\", \"Var\" and \"Vaucluse\" Departments. The strains isolated from canine and human visceral Leishmaniasis had a malate dehydrogenase XI whereas Leishmania tropica had a MDH I; no wild animals have been found with Leishmaniasis.  The suburbs of the towns, the hills in the center of Marseilles or surrounding Toulon as well as the villages are the principal foci of Phlebotomus perniciousus (96%) as the vector. The biotopes are isolated houses with little gardens surrounded by dry-stone walls exhibiting holes named \"barbacanes\", with chalky soil and xerophytes. The killing of infected dogs is the best protection of men whereas keeping dogs in sandfly-proof kennels from twilight until one hour after sunrise is best in order to protect this animal. This is quite different from the observations made by RIOUX in the Cevennes."}
{"id": "PMID:7126", "title": "[Presence of Angiostrongylus cantonensis at la R\u00e9union].", "content": "The eosinophilic meningitis due to Angiostrongylus cantonensis is well known on Madagascar and on Mauritius Island, but was never described on Reunion Island. Two cases have been lately oberved in Doctor Jay's department at Gabriel Martin's hospital. Local achatines were dissected and contained larvae which, when absorbed by rats, were found in there brains ten days later. These larvae belong certainly to Angiostrongylus genus, but the species has not yet been found with certitude. Lately infested rats are passing through the normal laps of time for adult maturation until they will be sacrified for further examinations.", "contents": "[Presence of Angiostrongylus cantonensis at la R\u00e9union]. The eosinophilic meningitis due to Angiostrongylus cantonensis is well known on Madagascar and on Mauritius Island, but was never described on Reunion Island. Two cases have been lately oberved in Doctor Jay's department at Gabriel Martin's hospital. Local achatines were dissected and contained larvae which, when absorbed by rats, were found in there brains ten days later. These larvae belong certainly to Angiostrongylus genus, but the species has not yet been found with certitude. Lately infested rats are passing through the normal laps of time for adult maturation until they will be sacrified for further examinations."}
{"id": "PMID:7133", "title": "Mucocutaneous lymph node syndrome with coronary artery aneurysm.", "content": "A white North American girl with clinical features of the mucocutaneous lymph node syndrome had a myocardial infarct and angiographic evidence of a coronary artery aneurysm and mitral regurgitation. The mucocutaneous lymph node syndrome has been extensively diagnosed in Japan in recent years. It appears to be a distinct entity, although not precisely separated from polyarteritis nodosa in childhood. The condition may be more common than previously realized.", "contents": "Mucocutaneous lymph node syndrome with coronary artery aneurysm. A white North American girl with clinical features of the mucocutaneous lymph node syndrome had a myocardial infarct and angiographic evidence of a coronary artery aneurysm and mitral regurgitation. The mucocutaneous lymph node syndrome has been extensively diagnosed in Japan in recent years. It appears to be a distinct entity, although not precisely separated from polyarteritis nodosa in childhood. The condition may be more common than previously realized."}
{"id": "PMID:7134", "title": "Mucocutaneous lymph node syndrome in the United States.", "content": "Sixteen patients with an unusual and distinct symptom complex were encountered during a four-year period. Principal features of this syndrome are (1) fever lasting more than seven days; (2) conjunctival injection; (3) changes in the mouth consisting of erythema of the oropharynx, \"strawberry tongue\", and erythema of the lips; (4) indurative edema of hands and feet with palm and sole erythema followed by desquamation of the fingertips; and (5) an erythematous rash. Associated features were lymphadenopathy, pyuria, aseptic meningitis, diarrhea, arthritis, and arthralgia. Although usually a self-limited illness, one patient died with massive coronary artery thrombosis on the 19th day of illness. This syndrome appears to be clinically and pathologically similar to mucocutaneous lymph node syndrome, an illness prevalent in Japan but previously unrecognized by American clinicians. Pathologic features suggest a relationship to infantile periarteritis nodosa.", "contents": "Mucocutaneous lymph node syndrome in the United States. Sixteen patients with an unusual and distinct symptom complex were encountered during a four-year period. Principal features of this syndrome are (1) fever lasting more than seven days; (2) conjunctival injection; (3) changes in the mouth consisting of erythema of the oropharynx, \"strawberry tongue\", and erythema of the lips; (4) indurative edema of hands and feet with palm and sole erythema followed by desquamation of the fingertips; and (5) an erythematous rash. Associated features were lymphadenopathy, pyuria, aseptic meningitis, diarrhea, arthritis, and arthralgia. Although usually a self-limited illness, one patient died with massive coronary artery thrombosis on the 19th day of illness. This syndrome appears to be clinically and pathologically similar to mucocutaneous lymph node syndrome, an illness prevalent in Japan but previously unrecognized by American clinicians. Pathologic features suggest a relationship to infantile periarteritis nodosa."}
{"id": "PMID:7135", "title": "Inhibition of nocturnal acid secretion in duodenal ulcer patients by an H-2 histamine antagonist-cimetidine. A controlled double-blind investigation.", "content": "A new H-2-receptor antagonist, cimetidine, was tested as to its ability to suppress overnight gastric acid secretion in 8 male duodenal ulcer patients. In a double-blind controlled investigation, each volunteer was studied during four consecutive nights. In randomized order they received either 100, 200, or 300 mg of cimetidine or a placebo. No untoward clinical orlaboratory effects of the drug were found. Single-dose oral administration of 300 mg cimetidine caused a significant (P less than 0.05) inhibition of overnight gastric acid secretion for an 8-hr period, with the intragastric pH staying between 3.5-6.0. Cimetidine, because of its potent gastric acid inhibitory effect, may become an important therapeutic agent in the management of peptic ulcer disease.", "contents": "Inhibition of nocturnal acid secretion in duodenal ulcer patients by an H-2 histamine antagonist-cimetidine. A controlled double-blind investigation. A new H-2-receptor antagonist, cimetidine, was tested as to its ability to suppress overnight gastric acid secretion in 8 male duodenal ulcer patients. In a double-blind controlled investigation, each volunteer was studied during four consecutive nights. In randomized order they received either 100, 200, or 300 mg of cimetidine or a placebo. No untoward clinical orlaboratory effects of the drug were found. Single-dose oral administration of 300 mg cimetidine caused a significant (P less than 0.05) inhibition of overnight gastric acid secretion for an 8-hr period, with the intragastric pH staying between 3.5-6.0. Cimetidine, because of its potent gastric acid inhibitory effect, may become an important therapeutic agent in the management of peptic ulcer disease."}
{"id": "PMID:7136", "title": "Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. A pilot study.", "content": "Four patients with severe chronic radiation enteritis and/or colitis were treated with anti-inflammatory drugs that are used conventionally in the treatment of idiopathic inflammatory bowel disease. Salicylazosulfapyridine (SASP) was used in the treatment of all four patients, while one patient received oral prednisone together with SASP. All four patients were treated and observed for over one year, with follow-up observations now extending to over three years. The four patients showed striking clinical improvement, accompanied by improvement in the radiographic appearance of affected bowel, complete or almost complete in three and incomplete in the fourth patient. The results of this pilot investigation are encouraging and call for wider clinical trials of the same  and related drugs in larger groups of patients with chronic radiation enterocolitis, a serious condition that has until now not been successfully treated with drugs.", "contents": "Treatment of chronic radiation enteritis and colitis with salicylazosulfapyridine and systemic corticosteroids. A pilot study. Four patients with severe chronic radiation enteritis and/or colitis were treated with anti-inflammatory drugs that are used conventionally in the treatment of idiopathic inflammatory bowel disease. Salicylazosulfapyridine (SASP) was used in the treatment of all four patients, while one patient received oral prednisone together with SASP. All four patients were treated and observed for over one year, with follow-up observations now extending to over three years. The four patients showed striking clinical improvement, accompanied by improvement in the radiographic appearance of affected bowel, complete or almost complete in three and incomplete in the fourth patient. The results of this pilot investigation are encouraging and call for wider clinical trials of the same  and related drugs in larger groups of patients with chronic radiation enterocolitis, a serious condition that has until now not been successfully treated with drugs."}
{"id": "PMID:7137", "title": "Elevated serum gamma-glutamyl-transferase (transpeptidase) and histological liver damage in alcoholism.", "content": "In 66 alcoholic patients, serum gamma-glutamyl-transferase (transpeptidase) (GGTP) activity was studied in relationship to other biochemical liver function tests and histological liver damage. Elevated serum GGTP activity was the single most common biochemical abnormality (74%) and, when present was accompanied by histological abnormalities in all but one case. In seven patients, including two with alcoholic cirrhosis, this was the only biochemical abnormality. The mean serum GGTP was highest in the cirrhotic group. There was some correlation between serum GGTP activity and the degree of histological hepato-cellular necrosis. The values showed a wide scatter, however, and 12 patients had normal serum GGTP activity when histological damage was present. While elevated serum GGTP levels in alcoholism may be partly related to structural liver damage, other mechanisms, such as hepatic microsomal enzyme induction or alcoholic pancreatic damage, may also play a role.", "contents": "Elevated serum gamma-glutamyl-transferase (transpeptidase) and histological liver damage in alcoholism. In 66 alcoholic patients, serum gamma-glutamyl-transferase (transpeptidase) (GGTP) activity was studied in relationship to other biochemical liver function tests and histological liver damage. Elevated serum GGTP activity was the single most common biochemical abnormality (74%) and, when present was accompanied by histological abnormalities in all but one case. In seven patients, including two with alcoholic cirrhosis, this was the only biochemical abnormality. The mean serum GGTP was highest in the cirrhotic group. There was some correlation between serum GGTP activity and the degree of histological hepato-cellular necrosis. The values showed a wide scatter, however, and 12 patients had normal serum GGTP activity when histological damage was present. While elevated serum GGTP levels in alcoholism may be partly related to structural liver damage, other mechanisms, such as hepatic microsomal enzyme induction or alcoholic pancreatic damage, may also play a role."}
{"id": "PMID:7138", "title": "Search for epizootic-like Venezuelan encephalitis virus at enzootic habitats in Guatemala during 1969-1971.", "content": "Seventy-four strains of Venezuelan encephalitis (VE) virus recovered from sentinel hamsters or mosquitoes at enzootic habitats in Guatemala in the two years following the 1969 epidemic-equine epizootic were examined for ability to produce small plaques in Vero African green monkey kidney cell cultures, like isolates obtained during the epizootic. (a) One strain recovered from a sentinel hamster in late October 1969 at an enzootic habitat near the epicenter of the hemagglutination-inhibition (HI) and equine-virulence properties like epizootic virus; this strain retained its small plaque characteristic after inoculation and recovery from bloods of three horses. (b) None of the other 73 strains produced uniformly small plaques, but 31 formed a few small plaques among large ones. Virions from small plaques of five strains were cloned twice in Vero cell cultures. Four clones produced uniformly small plaques after one more passage in Vero cells; three had hemagglutination-pH properties compatible with epizootic virus or intermediate between epizootic and enzootic virus, but HI tests with these three hemagglutinins or with antibody to the fourth cloned strain showed them to be like Central American enzootic virus. One of three cloned strains tested in horses produced encephalitis and death in one of four horses; another strain produced encephalitis with recovery in one of two horses. (c) Thus these small Vero plaque clones resembled Central American enzootic strains of VE virus in HI and equine-virulence tests, and the small Vero plaque characteristic was not a satisfactory marker for consistently isolating equine-virulent, epizootic VE virions. Nevertheless, this technic led to recognition of one epizootic strain isolated at an enzootic habitat in Guatemala at the end of 1969 outbreak. Whether this strain was there before the outbreak or subsequently penetrated the habitat is uncertain. During the next two years, this strain did not become dominant in that enzootic focus.", "contents": "Search for epizootic-like Venezuelan encephalitis virus at enzootic habitats in Guatemala during 1969-1971. Seventy-four strains of Venezuelan encephalitis (VE) virus recovered from sentinel hamsters or mosquitoes at enzootic habitats in Guatemala in the two years following the 1969 epidemic-equine epizootic were examined for ability to produce small plaques in Vero African green monkey kidney cell cultures, like isolates obtained during the epizootic. (a) One strain recovered from a sentinel hamster in late October 1969 at an enzootic habitat near the epicenter of the hemagglutination-inhibition (HI) and equine-virulence properties like epizootic virus; this strain retained its small plaque characteristic after inoculation and recovery from bloods of three horses. (b) None of the other 73 strains produced uniformly small plaques, but 31 formed a few small plaques among large ones. Virions from small plaques of five strains were cloned twice in Vero cell cultures. Four clones produced uniformly small plaques after one more passage in Vero cells; three had hemagglutination-pH properties compatible with epizootic virus or intermediate between epizootic and enzootic virus, but HI tests with these three hemagglutinins or with antibody to the fourth cloned strain showed them to be like Central American enzootic virus. One of three cloned strains tested in horses produced encephalitis and death in one of four horses; another strain produced encephalitis with recovery in one of two horses. (c) Thus these small Vero plaque clones resembled Central American enzootic strains of VE virus in HI and equine-virulence tests, and the small Vero plaque characteristic was not a satisfactory marker for consistently isolating equine-virulent, epizootic VE virions. Nevertheless, this technic led to recognition of one epizootic strain isolated at an enzootic habitat in Guatemala at the end of 1969 outbreak. Whether this strain was there before the outbreak or subsequently penetrated the habitat is uncertain. During the next two years, this strain did not become dominant in that enzootic focus."}
{"id": "PMID:7139", "title": "Search for persistent epizootic Venezuelan encephalitis virus in Guatemala, El Salvador and Nicaragua during 1970-1975.", "content": "Evidence was sought during 1970-1975 of persistence of equine-virulent Venezuelan encephalitis (VE) virus in regions of Central America that were heavily involved in the epidemic-equine epizootic of 1969. (a) Four sentinel horses were exposed in an arid, upland region of the Atlantic drainage of Guatemala during August-October 1970, but no horse became infected. (b) The epicenter region of the 1969 outbreak, in southwestern Guatemala and southwestern El Salvador, was studied during July 1970-February 1974; no antibody developed in sentinel horses, sentinel hamsters did not die, mosquitoes yielded no virus, wild rats had no detectable VE virus HI antibody. Unexplained decreases in populations of wild terrestrial mammals possibly limited maintenance of VE virus. However, mosquitoes were plentiful and present in the same species composition found at a focus of enzootic VE virus about 35 km northwest of the epicenter region. (c) In studies at two Guatemalan ranches near the epicenter, where horses died in 1969, VE viruse infected sentinel horses along one of three lakes on one ranch during the wet season of 1972 but not during the dry or wet seasons of 1973; the titers of neutralizing antibodies in these four horses were higher against an enzootic strain of VE virus than against an epizootic strain. During 1970 and 1971, VE virus was isolated from sentinel hamsters exposed at a marsh on the other ranch, but Vero plaque characteristics were those of enzootic VE virus. (d) The only epizootic activity of VE virus discovered in Central America in 1970-1975 occurred in Nicaragua between April and June 1972. Several hundred horses died, and N antibody, like that engendered by epizootic virus, was found in two young, unvaccinated horses. Whether this represented persistence of epizootic VE virus or reintroduction of virus is unknown.", "contents": "Search for persistent epizootic Venezuelan encephalitis virus in Guatemala, El Salvador and Nicaragua during 1970-1975. Evidence was sought during 1970-1975 of persistence of equine-virulent Venezuelan encephalitis (VE) virus in regions of Central America that were heavily involved in the epidemic-equine epizootic of 1969. (a) Four sentinel horses were exposed in an arid, upland region of the Atlantic drainage of Guatemala during August-October 1970, but no horse became infected. (b) The epicenter region of the 1969 outbreak, in southwestern Guatemala and southwestern El Salvador, was studied during July 1970-February 1974; no antibody developed in sentinel horses, sentinel hamsters did not die, mosquitoes yielded no virus, wild rats had no detectable VE virus HI antibody. Unexplained decreases in populations of wild terrestrial mammals possibly limited maintenance of VE virus. However, mosquitoes were plentiful and present in the same species composition found at a focus of enzootic VE virus about 35 km northwest of the epicenter region. (c) In studies at two Guatemalan ranches near the epicenter, where horses died in 1969, VE viruse infected sentinel horses along one of three lakes on one ranch during the wet season of 1972 but not during the dry or wet seasons of 1973; the titers of neutralizing antibodies in these four horses were higher against an enzootic strain of VE virus than against an epizootic strain. During 1970 and 1971, VE virus was isolated from sentinel hamsters exposed at a marsh on the other ranch, but Vero plaque characteristics were those of enzootic VE virus. (d) The only epizootic activity of VE virus discovered in Central America in 1970-1975 occurred in Nicaragua between April and June 1972. Several hundred horses died, and N antibody, like that engendered by epizootic virus, was found in two young, unvaccinated horses. Whether this represented persistence of epizootic VE virus or reintroduction of virus is unknown."}
{"id": "PMID:7140", "title": "A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells.", "content": "The graft-versus-host (GVH) reactivity of uremic and control spleen cells was studied by popliteal lymph node assay in the rat. The reaction evoked by cells from animals with severe uremia was conspicuously weaker than that evoked by control cells. The magnitude of the GVH reaction induced by control cells was directly proportional to dose, while with the uremic cells the same increases in dose led only to insignificant increases in the strength of the GVH reaction. When mixtures of syngeneic control and uremic cells were used, the GVH reactivity of the control cells was suppressed. The activity of uremic spleen cells can be enhanced (restored) by removal of the sub-population of cells adherent to glass wool. The GVH reaction induced by uremic cells so treated became directly proportional to dose. The removal of the adherent cell population from the uremic spleen cell suspension also led to the disappearance of the suppressor effect in mixtures of control and uremic cells. These results indicate that a decrease in GVH activity of rat uremic spleen cells is due to an increase in suppressor cell activity in the uremic spleen cell population.", "contents": "A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells. The graft-versus-host (GVH) reactivity of uremic and control spleen cells was studied by popliteal lymph node assay in the rat. The reaction evoked by cells from animals with severe uremia was conspicuously weaker than that evoked by control cells. The magnitude of the GVH reaction induced by control cells was directly proportional to dose, while with the uremic cells the same increases in dose led only to insignificant increases in the strength of the GVH reaction. When mixtures of syngeneic control and uremic cells were used, the GVH reactivity of the control cells was suppressed. The activity of uremic spleen cells can be enhanced (restored) by removal of the sub-population of cells adherent to glass wool. The GVH reaction induced by uremic cells so treated became directly proportional to dose. The removal of the adherent cell population from the uremic spleen cell suspension also led to the disappearance of the suppressor effect in mixtures of control and uremic cells. These results indicate that a decrease in GVH activity of rat uremic spleen cells is due to an increase in suppressor cell activity in the uremic spleen cell population."}
{"id": "PMID:7141", "title": "Coronary vascular sympathetic beta-receptor innervation.", "content": "Recent studies indicate that coronary vessels have alpha- and beta-2-adrenergic receptors and that the alpha receptors are functionally innervated. We studied whether the beta-2-vasodilator receptors are functionally innervated, using a dog in situ modified Langendorff preparation with constant coronary perfusion pressure. The beating, nonworking heart and systemic circulation were supported with a pump oxygenator. Stimulation of the left stellate ganglion increased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values. After beta-1-receptor blockade (practolol, 10 mg/kg), stellate stimulation decreased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values, revealing alpha-receptor vasoconstriction. After the addition of alpha-receptor blockade (Dibozane, 5 mg/kg), stellate stimulation increased coronary blood flow and coronary sinus oxygen tension a small amount from prestimulation values. Finally, after the addition of beta-2-receptor blockade (propranolol, 2 mg/kg), stellate stimulation increased flow and coronary sinus oxygen tension slightly from prestimulation control values. Direct intracoronary injections of isoproterenol, norepinephrine, and epinephrine gave results consistent with the presence of beta-1 myocardial receptors and alpha and beta-2 coronary receptors. We conclude that there is little functional innervation of coronary vascular beta-2 receptors. Intracoronary injections of isoproterenol and epinephrine activated beta-2-receptor coronary vasodilation after beta-1-receptor blockade, but norepinephrine did not.", "contents": "Coronary vascular sympathetic beta-receptor innervation. Recent studies indicate that coronary vessels have alpha- and beta-2-adrenergic receptors and that the alpha receptors are functionally innervated. We studied whether the beta-2-vasodilator receptors are functionally innervated, using a dog in situ modified Langendorff preparation with constant coronary perfusion pressure. The beating, nonworking heart and systemic circulation were supported with a pump oxygenator. Stimulation of the left stellate ganglion increased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values. After beta-1-receptor blockade (practolol, 10 mg/kg), stellate stimulation decreased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values, revealing alpha-receptor vasoconstriction. After the addition of alpha-receptor blockade (Dibozane, 5 mg/kg), stellate stimulation increased coronary blood flow and coronary sinus oxygen tension a small amount from prestimulation values. Finally, after the addition of beta-2-receptor blockade (propranolol, 2 mg/kg), stellate stimulation increased flow and coronary sinus oxygen tension slightly from prestimulation control values. Direct intracoronary injections of isoproterenol, norepinephrine, and epinephrine gave results consistent with the presence of beta-1 myocardial receptors and alpha and beta-2 coronary receptors. We conclude that there is little functional innervation of coronary vascular beta-2 receptors. Intracoronary injections of isoproterenol and epinephrine activated beta-2-receptor coronary vasodilation after beta-1-receptor blockade, but norepinephrine did not."}
{"id": "PMID:7142", "title": "Uric acid excretion by the pig kidney.", "content": "The handling of uric acid by the pig kidney has been investigated during continuous urate infusion in unrestrained, unanesthetized animals. Urate-to-inulin clearance rates in excess of 1 were found under all experimental conditions, demonstrating only net secretion by the pig kidney. The demonstration of a secretory maximum was precluded owing to a progressive reduction in the GFR associated with high rates of urate infusion. Urate clearance was independent of urine flow rate up to 10 ml/min. The administration of probenecid inhibited urate secretion, but urate-to-inulin clearance ratios below unity were not observed. Pyrazinamide or pyrazinoic acid, at doses which either inhibited secretion or promoted uricosuria in other species, did not alter urate excretion in the pig. Probenecid together with pyrazinamide exerted the same inhibitory effect on urate secretion as probenecid alone. Pyrazinoic acid was reabsorbed at all infusion rates. It is concluded that the pig kidney eliminates uric acid by filtration and secretion only.", "contents": "Uric acid excretion by the pig kidney. The handling of uric acid by the pig kidney has been investigated during continuous urate infusion in unrestrained, unanesthetized animals. Urate-to-inulin clearance rates in excess of 1 were found under all experimental conditions, demonstrating only net secretion by the pig kidney. The demonstration of a secretory maximum was precluded owing to a progressive reduction in the GFR associated with high rates of urate infusion. Urate clearance was independent of urine flow rate up to 10 ml/min. The administration of probenecid inhibited urate secretion, but urate-to-inulin clearance ratios below unity were not observed. Pyrazinamide or pyrazinoic acid, at doses which either inhibited secretion or promoted uricosuria in other species, did not alter urate excretion in the pig. Probenecid together with pyrazinamide exerted the same inhibitory effect on urate secretion as probenecid alone. Pyrazinoic acid was reabsorbed at all infusion rates. It is concluded that the pig kidney eliminates uric acid by filtration and secretion only."}
{"id": "PMID:7143", "title": "Heart rate and rhythm and intracranial pressure.", "content": "Cardiac slowing during elevated intracranial pressure (ICP) could be due to direct activation of central nervous system (CNS) centers or it may be secondary to baroreceptor reflexes activated by the associated pressor response. In five pentobarbital-anesthetized dogs when ICP was raised to 50 mmHg the heart rate decreased 34.4 beats/min (+/-4.8 SE). This cardiac slowing occurred when ICP was elevated after sinoaortic denervation (-24 +/- 4.43 beats/min) and also during elevated ICP when changes in arterial pressure were prevented (-32.3 +/- 4.25 beats/min). These results indicate that the cardiac slowing is largely of CNS origin. In dogs given morphine with pentobarbital to achieve slower heart rates, raising ICP to 50 mmHg by left-sided intracranial balloon inflation led to cardiac dysrhythmias in 9 of 12 dogs. By contrast, raising ICP to 50 mmHg by right-sided intracranial balloon inflation only produced progressive sinus bradycardia. These responses were related to a combined enhancement of vagal and sympathetic activity. Differences observed between right- and left-sides balloon inflation may be partly related to asymmetrical engagement of the cardiac autonomic nerves. The results suggest that left-sided intracranial lesions are more likely to produce cardiac dysrhythmias.", "contents": "Heart rate and rhythm and intracranial pressure. Cardiac slowing during elevated intracranial pressure (ICP) could be due to direct activation of central nervous system (CNS) centers or it may be secondary to baroreceptor reflexes activated by the associated pressor response. In five pentobarbital-anesthetized dogs when ICP was raised to 50 mmHg the heart rate decreased 34.4 beats/min (+/-4.8 SE). This cardiac slowing occurred when ICP was elevated after sinoaortic denervation (-24 +/- 4.43 beats/min) and also during elevated ICP when changes in arterial pressure were prevented (-32.3 +/- 4.25 beats/min). These results indicate that the cardiac slowing is largely of CNS origin. In dogs given morphine with pentobarbital to achieve slower heart rates, raising ICP to 50 mmHg by left-sided intracranial balloon inflation led to cardiac dysrhythmias in 9 of 12 dogs. By contrast, raising ICP to 50 mmHg by right-sided intracranial balloon inflation only produced progressive sinus bradycardia. These responses were related to a combined enhancement of vagal and sympathetic activity. Differences observed between right- and left-sides balloon inflation may be partly related to asymmetrical engagement of the cardiac autonomic nerves. The results suggest that left-sided intracranial lesions are more likely to produce cardiac dysrhythmias."}
{"id": "PMID:7144", "title": "Effects of hypoxia and Freon 12 on mechanics of cardiac contraction.", "content": "Data are presented which indicate that the mechanism of tension depression and subsequent recovery from dichlorodifluoromethane (Freon 12), an aerosol gas recently described as a potent cardiac depressant agent, differs from that of hypoxia. To analyze these differences, 22 rat papillary muscles, contracting isometrically in a myograph, were studied during and subsequent to 15-min interventions of of hypoxia. Freon 12 with adequate oxygenation, or Freon 12 combined with hypoxia. During each of the three interventions the developed force (F) was markedly depressed, while peak shortening velocity (Vpm) was selectively more depressed by Freon and Freon combined with hypoxia than by hypoxia alone. While hypoxia shortened the time to peak force (TTP) and one-half relaxation time (RT1/2) markedly, Freon 12 with adequate oxygenation slightly shortened RT1/2 (P is less than 0.001) but failed to shorten TTP significantly. In contrast, Freon 12 administered during hypoxia shortened TTP and RT1/2 significantly (P is less than 0.001), more than did hypoxia or Freon 12 alone. Posthypoxic prolongation of TTP and RT1/2 was not seen during recovery from Freon 12. This prolongation was depressed during recovery from Freon 12 given either during hypoxia or during recovery from hypoxia. The results indicate that Freon 12 and hypoxia act synergically, although the mechanisms through which they mediate their actions on myocardial tissue are not identical.", "contents": "Effects of hypoxia and Freon 12 on mechanics of cardiac contraction. Data are presented which indicate that the mechanism of tension depression and subsequent recovery from dichlorodifluoromethane (Freon 12), an aerosol gas recently described as a potent cardiac depressant agent, differs from that of hypoxia. To analyze these differences, 22 rat papillary muscles, contracting isometrically in a myograph, were studied during and subsequent to 15-min interventions of of hypoxia. Freon 12 with adequate oxygenation, or Freon 12 combined with hypoxia. During each of the three interventions the developed force (F) was markedly depressed, while peak shortening velocity (Vpm) was selectively more depressed by Freon and Freon combined with hypoxia than by hypoxia alone. While hypoxia shortened the time to peak force (TTP) and one-half relaxation time (RT1/2) markedly, Freon 12 with adequate oxygenation slightly shortened RT1/2 (P is less than 0.001) but failed to shorten TTP significantly. In contrast, Freon 12 administered during hypoxia shortened TTP and RT1/2 significantly (P is less than 0.001), more than did hypoxia or Freon 12 alone. Posthypoxic prolongation of TTP and RT1/2 was not seen during recovery from Freon 12. This prolongation was depressed during recovery from Freon 12 given either during hypoxia or during recovery from hypoxia. The results indicate that Freon 12 and hypoxia act synergically, although the mechanisms through which they mediate their actions on myocardial tissue are not identical."}
{"id": "PMID:7146", "title": "Management of interpersonal issues in systematic desensitization.", "content": "The authors use the management of typical clinical problems that arise during systematic desensitization as a model for the analysis and solution of problems associated with behavior therapy techniques. Three main problem areas are considered: initiation of the technique, therapist and patient difficulties, and therapeutic decision making. The discussion is designed primarily to help therapists with varied backgrounds to deal with clinical issues that arise in the application of behavior therapy techniques such as systematic desensitization.", "contents": "Management of interpersonal issues in systematic desensitization. The authors use the management of typical clinical problems that arise during systematic desensitization as a model for the analysis and solution of problems associated with behavior therapy techniques. Three main problem areas are considered: initiation of the technique, therapist and patient difficulties, and therapeutic decision making. The discussion is designed primarily to help therapists with varied backgrounds to deal with clinical issues that arise in the application of behavior therapy techniques such as systematic desensitization."}
{"id": "PMID:7145", "title": "Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes.", "content": "Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.", "contents": "Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes. Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart."}
{"id": "PMID:7148", "title": "Arbovirus surveillance in six states during 1972.", "content": "A virus surveillance project was established and maintained during 1972 along 10 major river drainages in six states. Mosquitoes, biting flies, and blood specimens from sentinel equines were collected during 83 field trip visits to 141 arthropod collecting sites and 22 sentinel locations from April into December 1972. There were 173,074 mosquitoes tested and 303 arboviruses isolated from 11 of 41 species. From 13,388 biting flies tested, 8 arbovirus isolations were obtained in 1 of 5 species. There was no isolation of Venezuelan equine encephalitis (VEE) virus. Western equine encephalitis (WEE) virus isolates were the most numerous and were followed by Turlock, St. Louis encephalitis, Hart Park, California encephalitis, and Bunyamwera (BUN) group viruses. The first isolation of WEE from the mosquito Cullex (Mel). erraticus is reported, as is the extension of the ranges for Buttonwillow virus from California to New Mexico and Texas. Also a single isolation of the BUN group from Culicoides variipennis extends the range of this virus-vector relationship from California to Texas. New distribution records for mosquito species previously unreported for Arizona, Louisana, New Mexico, and Oklahoma are reported. The sentinel burros detected WEE serologic conversions at two sites in New Mexico and at one in Texas. The surveillance project provided state and federal officials with current information on the status of arbovirus activity, including the absence of VEE activity during 1972, and it demonstrated the existence of the potential for WEE epizootics and epidemics throughout a wide geographic area of the Western United States.", "contents": "Arbovirus surveillance in six states during 1972. A virus surveillance project was established and maintained during 1972 along 10 major river drainages in six states. Mosquitoes, biting flies, and blood specimens from sentinel equines were collected during 83 field trip visits to 141 arthropod collecting sites and 22 sentinel locations from April into December 1972. There were 173,074 mosquitoes tested and 303 arboviruses isolated from 11 of 41 species. From 13,388 biting flies tested, 8 arbovirus isolations were obtained in 1 of 5 species. There was no isolation of Venezuelan equine encephalitis (VEE) virus. Western equine encephalitis (WEE) virus isolates were the most numerous and were followed by Turlock, St. Louis encephalitis, Hart Park, California encephalitis, and Bunyamwera (BUN) group viruses. The first isolation of WEE from the mosquito Cullex (Mel). erraticus is reported, as is the extension of the ranges for Buttonwillow virus from California to New Mexico and Texas. Also a single isolation of the BUN group from Culicoides variipennis extends the range of this virus-vector relationship from California to Texas. New distribution records for mosquito species previously unreported for Arizona, Louisana, New Mexico, and Oklahoma are reported. The sentinel burros detected WEE serologic conversions at two sites in New Mexico and at one in Texas. The surveillance project provided state and federal officials with current information on the status of arbovirus activity, including the absence of VEE activity during 1972, and it demonstrated the existence of the potential for WEE epizootics and epidemics throughout a wide geographic area of the Western United States."}
{"id": "PMID:7149", "title": "A note on the use of trypsinized human group O erythrocytes in arbovirus titrations.", "content": "Twenty-two different arbovirus antigens derived from five antigenic groups were examined for their ability to agglutinate normal and trypsinized human group O erythrocytes. Trypsinization rendered the cells susceptible to agglutination by 18 viruses,chiefly in the pH 5.85 to 6.2 range, yielding hemagglutinin titers comparable with those obtained with gander cells at their optimal pH.", "contents": "A note on the use of trypsinized human group O erythrocytes in arbovirus titrations. Twenty-two different arbovirus antigens derived from five antigenic groups were examined for their ability to agglutinate normal and trypsinized human group O erythrocytes. Trypsinization rendered the cells susceptible to agglutination by 18 viruses,chiefly in the pH 5.85 to 6.2 range, yielding hemagglutinin titers comparable with those obtained with gander cells at their optimal pH."}
{"id": "PMID:7150", "title": "Respiratory effects of 'lissive\" anaesthesia using gallamine.", "content": "'Lissive anaesthesia', the administration of a small dose of a non-depolarising muscle relaxant to a patient breathing nitrous oxide, oxygen and an anaesthetic vapour, is a technique popularly employed for minor procedures. In this study, the effects of intravenous gallamine triethiodide (40 mg) on the blood-gas status of 20 patients under general anaesthesia with oxygen, nitrous oxide and halothane after pethidine and atropine premedication, were assessed. The results are compared with those obtained from a control group of 10 patients anaesthetised in an identical manner, but omitting the muscle relaxant drug. All patients in both the relaxant and control groups in this study developed respiratory acidaemia. The rise in mean arterial carbon dioxide tension was, however, greater after injection of gallamine. Significant hypoxia or metabolic acidaemia was not encountered, except in one grossly obese patient in the gallamine group. The implications of these findings are discussed.", "contents": "Respiratory effects of 'lissive\" anaesthesia using gallamine. 'Lissive anaesthesia', the administration of a small dose of a non-depolarising muscle relaxant to a patient breathing nitrous oxide, oxygen and an anaesthetic vapour, is a technique popularly employed for minor procedures. In this study, the effects of intravenous gallamine triethiodide (40 mg) on the blood-gas status of 20 patients under general anaesthesia with oxygen, nitrous oxide and halothane after pethidine and atropine premedication, were assessed. The results are compared with those obtained from a control group of 10 patients anaesthetised in an identical manner, but omitting the muscle relaxant drug. All patients in both the relaxant and control groups in this study developed respiratory acidaemia. The rise in mean arterial carbon dioxide tension was, however, greater after injection of gallamine. Significant hypoxia or metabolic acidaemia was not encountered, except in one grossly obese patient in the gallamine group. The implications of these findings are discussed."}
{"id": "PMID:7151", "title": "Anaesthetic induction for Caesarean section with propanidid.", "content": "Propanidid was used for the induction of anaesthesia at Caesarean section in 50 healthy mothers. All parturients were considered to have normal placental function. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxant and controlled ventilation. The patients were tilted laterally with a 15 degrees rubber wedge during the procedure in order to obviate the effects of aorta-caval occlusion. At the time of delivery, arterial blood was drawn from the mother and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. The results obtained are compared with those previously reported in a similar series anaesthetised with thiopentone, gas, oxygen and relaxant. Maternal blood-gas and acid-base levels were similar in the two groups at delivery. The clinical status of the infants in the present series, as judged by the modified Apgar score at 2 minutes after birth, was satisfactory. Umbilical venous and arterial pH values after propanidid were both 0-054 units (P less than 0-001) less than those following thiopentone; and average base deficits were 3-1 (Uv) and 3-9 (Ua) mEq/litre greater after propanidid (P less than 0-001). Mean oxygen levels in the umbilical cord bloods were 8-0 (Uv) and 3-5 (Ua) mmHg lower (P less than 0-001 & P less than 0-025 respectively) in the propanidid group. Derived oxygen contents was also significantly less than in the previous thiopentone series. (Ma-Uv) and (Ma-Ua) gradients were 0-053 and 0-051 pH units higher after propanidid than that following thiopentone (P less than 0-001). Mean (Ma-Uv) and (Ma-Ua) base deficits were 3-5 and 3-9 mEq/litre greater (P less than 0-001). Five patients offered definite evidence of factual recall, of whom three experienced pain. Propanidid, therefore, appeared to be associated with a greater degree of foetal acidaemia than did thiopentone. In addition, painful factual recall during surgery was encountered in 6 percent of cases. It is concluded that propanidid, although theoretically offering advantages over thiopentone to the obstetric anaesthetist, in practice, did not fulfil this promise.", "contents": "Anaesthetic induction for Caesarean section with propanidid. Propanidid was used for the induction of anaesthesia at Caesarean section in 50 healthy mothers. All parturients were considered to have normal placental function. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxant and controlled ventilation. The patients were tilted laterally with a 15 degrees rubber wedge during the procedure in order to obviate the effects of aorta-caval occlusion. At the time of delivery, arterial blood was drawn from the mother and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. The results obtained are compared with those previously reported in a similar series anaesthetised with thiopentone, gas, oxygen and relaxant. Maternal blood-gas and acid-base levels were similar in the two groups at delivery. The clinical status of the infants in the present series, as judged by the modified Apgar score at 2 minutes after birth, was satisfactory. Umbilical venous and arterial pH values after propanidid were both 0-054 units (P less than 0-001) less than those following thiopentone; and average base deficits were 3-1 (Uv) and 3-9 (Ua) mEq/litre greater after propanidid (P less than 0-001). Mean oxygen levels in the umbilical cord bloods were 8-0 (Uv) and 3-5 (Ua) mmHg lower (P less than 0-001 & P less than 0-025 respectively) in the propanidid group. Derived oxygen contents was also significantly less than in the previous thiopentone series. (Ma-Uv) and (Ma-Ua) gradients were 0-053 and 0-051 pH units higher after propanidid than that following thiopentone (P less than 0-001). Mean (Ma-Uv) and (Ma-Ua) base deficits were 3-5 and 3-9 mEq/litre greater (P less than 0-001). Five patients offered definite evidence of factual recall, of whom three experienced pain. Propanidid, therefore, appeared to be associated with a greater degree of foetal acidaemia than did thiopentone. In addition, painful factual recall during surgery was encountered in 6 percent of cases. It is concluded that propanidid, although theoretically offering advantages over thiopentone to the obstetric anaesthetist, in practice, did not fulfil this promise."}
{"id": "PMID:7152", "title": "The use of AH8165 for Caesarian section.", "content": "The use of AH8165, a new non-depolarising relaxant, for Caesarian section is reported. The rapidity of action and the absence of significant placental transfer of the drug were confirmed. AH8165 has a definite place in obstetric anaesthesia.", "contents": "The use of AH8165 for Caesarian section. The use of AH8165, a new non-depolarising relaxant, for Caesarian section is reported. The rapidity of action and the absence of significant placental transfer of the drug were confirmed. AH8165 has a definite place in obstetric anaesthesia."}
{"id": "PMID:7155", "title": "Cerebral arterio-venous oxygen difference: a bedside test for cerebral death.", "content": "A bedside test is described which compares the patients cerebral arterio-venous oxygen difference with a predicted norm at various levels of arterial CO2 tension. In patients in coma depasse this difference is reduced and is unresponsive to variations in arterial carbon dioxide tension. The test also confirms lack of respiratory efforts in the presence of adequate carbon dioxide tension.", "contents": "Cerebral arterio-venous oxygen difference: a bedside test for cerebral death. A bedside test is described which compares the patients cerebral arterio-venous oxygen difference with a predicted norm at various levels of arterial CO2 tension. In patients in coma depasse this difference is reduced and is unresponsive to variations in arterial carbon dioxide tension. The test also confirms lack of respiratory efforts in the presence of adequate carbon dioxide tension."}
{"id": "PMID:7156", "title": "Flunitrazepam, a new benzodiazepine compound in general anaesthesia. Clinical and statistical considerations on the first thousand cases.", "content": "Flunitrazepam, a derivative of benzodiazepine was used for induction and maintenance of anaesthesia in 933 patients. The induction dose was from 1,786 to 2,053 mg. The total dose of 2-2.66 mg was sufficient for maintenance of hypnosis for about 2 hours. The undesirable side effects were very rare. The average time of hypnosis after a single dose of flunitrazepam was 50.1 sec. The sedative action of the drug lasted for some time after regaining of consciousness. In most patients there was no need for administration of analgetics during first 24 hours after the operation. The authors believe that surgical anaesthesia will greatly benefit from this drug.", "contents": "Flunitrazepam, a new benzodiazepine compound in general anaesthesia. Clinical and statistical considerations on the first thousand cases. Flunitrazepam, a derivative of benzodiazepine was used for induction and maintenance of anaesthesia in 933 patients. The induction dose was from 1,786 to 2,053 mg. The total dose of 2-2.66 mg was sufficient for maintenance of hypnosis for about 2 hours. The undesirable side effects were very rare. The average time of hypnosis after a single dose of flunitrazepam was 50.1 sec. The sedative action of the drug lasted for some time after regaining of consciousness. In most patients there was no need for administration of analgetics during first 24 hours after the operation. The authors believe that surgical anaesthesia will greatly benefit from this drug."}
{"id": "PMID:7162", "title": "[Constant outflow anesthesia with the combination of alfatesine and fentanyl].", "content": "In a previous work, the authors showed the value of administering Alfatesine, in interventions of long duration, at a constant rate by using an automatic syringe, and by combining it with destromoramide. In this new work the authors present an analagous study carried out in 47 subjects, in which dextromoramide was replaced by fentanyl. The automatic syringe used was the Braun Perfusor IV equipped with a 50 ml syringe containing 0.3 ml. of CT 13.41 and 0.006 mg. of fentanyl per ml. Induction was achieved at graduation 10, 14 ml of the mixture having been injected in approximately 60 seconds. Maintenance of anesthesia was ensured at graduation 6 corresponding to an hourly administration of 27 to 30 ml of the mixture (9 ml of CT 13.41 and 0.18 mg of fentanyl). The patients were adults of average weight 64 kg., who had undergone sometimes major orthopedic surgery, of an average duration of 161 mn. The results are looked at from the angle of quality of the anesthesia and of the awakening and of the side effects. They confirm the non-accumulation under these conditions of use and these doses of CT 13.41 used and reveals an analagous behaviour of fentanyl. Reserves are however made owing to the mode of elimination of fentanyl, on the use of such a technique in anuric patients or in renal insufficiency.", "contents": "[Constant outflow anesthesia with the combination of alfatesine and fentanyl]. In a previous work, the authors showed the value of administering Alfatesine, in interventions of long duration, at a constant rate by using an automatic syringe, and by combining it with destromoramide. In this new work the authors present an analagous study carried out in 47 subjects, in which dextromoramide was replaced by fentanyl. The automatic syringe used was the Braun Perfusor IV equipped with a 50 ml syringe containing 0.3 ml. of CT 13.41 and 0.006 mg. of fentanyl per ml. Induction was achieved at graduation 10, 14 ml of the mixture having been injected in approximately 60 seconds. Maintenance of anesthesia was ensured at graduation 6 corresponding to an hourly administration of 27 to 30 ml of the mixture (9 ml of CT 13.41 and 0.18 mg of fentanyl). The patients were adults of average weight 64 kg., who had undergone sometimes major orthopedic surgery, of an average duration of 161 mn. The results are looked at from the angle of quality of the anesthesia and of the awakening and of the side effects. They confirm the non-accumulation under these conditions of use and these doses of CT 13.41 used and reveals an analagous behaviour of fentanyl. Reserves are however made owing to the mode of elimination of fentanyl, on the use of such a technique in anuric patients or in renal insufficiency."}
{"id": "PMID:7163", "title": "[Combination of R3365 (piritramide) and dehydrobenzperidol in animals. Respiratory effects and analgesia].", "content": "1 -- Respiratory depression has been studied in the no anaesthetized rabbit by analysis of the blood gases after an injection of Piritramide (R 3365) and dehydrobenzperidol. 2 -- The respiratory depression induced by Piritramide alone is less important after an injection of dehydrobenzperidol; the most interessant cases are: -- mixture dehydrobenzperidol 400 mug/kg. Pirittramide 1000 mug/kg; --dehydrobenzperidol (400 mug/kg) injected 15 minutes before Piritramide (1000 mug/kg). 3 -- The addition of Dehydrobenzperidol does not take the analgesic activity of Piritramide decrease by it increases it.", "contents": "[Combination of R3365 (piritramide) and dehydrobenzperidol in animals. Respiratory effects and analgesia]. 1 -- Respiratory depression has been studied in the no anaesthetized rabbit by analysis of the blood gases after an injection of Piritramide (R 3365) and dehydrobenzperidol. 2 -- The respiratory depression induced by Piritramide alone is less important after an injection of dehydrobenzperidol; the most interessant cases are: -- mixture dehydrobenzperidol 400 mug/kg. Pirittramide 1000 mug/kg; --dehydrobenzperidol (400 mug/kg) injected 15 minutes before Piritramide (1000 mug/kg). 3 -- The addition of Dehydrobenzperidol does not take the analgesic activity of Piritramide decrease by it increases it."}
{"id": "PMID:7164", "title": "[Variations in the activity of various curarizing substances as a function of the time of administration].", "content": "This experiment was carried out upon the male-adulte-AF SPF-Wister Rat, anesthetized by the use of pentobarbital-Na at the only dosage of 40 mg/kg/IP and put under artificial ventilation. The animals were divided into two groups: Group I, \"diurnal animals\" curarized between 10 a.m and 4 p.m; Group 2, \"nocturnal animals\" curarized between 9 and 12 p.m. Four drugs of the curarimimetic (pachycurare, non-depolarizing) type: gallamine, D-tubocurarine, pancuronium and AH-8165 were studied at doses presenting the same activity. The total curarizing effect measured by the surface defined by the curve of curarization within ten mns was constantly and significantly lowered in \"nocturnal animals\": a 25 p. 100 diminution with gallamine, 20 p. 100 diminution with D-tubocurarine, 27 p. 100 diminution with pancuronium, 19 p. 100 diminution with AH-8165. The hypothesis is that this diminution in the action of curarizing substances may be, to a great extent, in keeping with the rise of their metabolism -- the hepatic enzymatic activity being, in the rat, a nocturnal animal, definitely increased during the night.", "contents": "[Variations in the activity of various curarizing substances as a function of the time of administration]. This experiment was carried out upon the male-adulte-AF SPF-Wister Rat, anesthetized by the use of pentobarbital-Na at the only dosage of 40 mg/kg/IP and put under artificial ventilation. The animals were divided into two groups: Group I, \"diurnal animals\" curarized between 10 a.m and 4 p.m; Group 2, \"nocturnal animals\" curarized between 9 and 12 p.m. Four drugs of the curarimimetic (pachycurare, non-depolarizing) type: gallamine, D-tubocurarine, pancuronium and AH-8165 were studied at doses presenting the same activity. The total curarizing effect measured by the surface defined by the curve of curarization within ten mns was constantly and significantly lowered in \"nocturnal animals\": a 25 p. 100 diminution with gallamine, 20 p. 100 diminution with D-tubocurarine, 27 p. 100 diminution with pancuronium, 19 p. 100 diminution with AH-8165. The hypothesis is that this diminution in the action of curarizing substances may be, to a great extent, in keeping with the rise of their metabolism -- the hepatic enzymatic activity being, in the rat, a nocturnal animal, definitely increased during the night."}
{"id": "PMID:7165", "title": "[2 cases of respiratory assistance with a membrane oxygenator].", "content": "The authors report two cases of artificial ventilation with the assistance of a membrane oxygenator that was used, on the one hand, in the case of a 'malignant pneumopathy' and, on the other hand, in the case of a cardio-respiratory failure after a complete mending of a tetralogy of Fallot. Recovery was obtained in the second case. They specify the method and the watching of anti-coagulation. They insist upon the merit of a re-injection of oxygenated blood into the ascending aorta. They recall the necessity to lay down instructions according to very strict criteria, by taking into account the degree and the visceral repercussions of hypoxia and the reversibility of lung lesions in so far as it is a matter of a very heavy palliative therapy upon whose efficiency it is difficult to pass a judgment.", "contents": "[2 cases of respiratory assistance with a membrane oxygenator]. The authors report two cases of artificial ventilation with the assistance of a membrane oxygenator that was used, on the one hand, in the case of a 'malignant pneumopathy' and, on the other hand, in the case of a cardio-respiratory failure after a complete mending of a tetralogy of Fallot. Recovery was obtained in the second case. They specify the method and the watching of anti-coagulation. They insist upon the merit of a re-injection of oxygenated blood into the ascending aorta. They recall the necessity to lay down instructions according to very strict criteria, by taking into account the degree and the visceral repercussions of hypoxia and the reversibility of lung lesions in so far as it is a matter of a very heavy palliative therapy upon whose efficiency it is difficult to pass a judgment."}
{"id": "PMID:7166", "title": "[The setting up of a computer system for records of first entries at the emergency medical assistance service in Montpellier].", "content": "The setting up of a computing device to exploit the files of first transports at the MONTPELLIER SAMU was started essentially in order to constitute a document both accurate and of easy access, able to memorize the physical and mental behaviour of a patient in a transient state. The results thus obtained include: 1 -- An analytical study with a part devoted to general data such as the number of injured people or of patients, the number of calls from various sources, the means of intervention etc. and a more specific part dealing with type of accident the determination of the traumatic impacts, the first therapy etc.; 2 -- A synthetical study that constitutes the second phase of the dealing with information thanks to the drawing up of graphs indicating the number of calls per accident according to the time, the age, the number of serious cases etc.", "contents": "[The setting up of a computer system for records of first entries at the emergency medical assistance service in Montpellier]. The setting up of a computing device to exploit the files of first transports at the MONTPELLIER SAMU was started essentially in order to constitute a document both accurate and of easy access, able to memorize the physical and mental behaviour of a patient in a transient state. The results thus obtained include: 1 -- An analytical study with a part devoted to general data such as the number of injured people or of patients, the number of calls from various sources, the means of intervention etc. and a more specific part dealing with type of accident the determination of the traumatic impacts, the first therapy etc.; 2 -- A synthetical study that constitutes the second phase of the dealing with information thanks to the drawing up of graphs indicating the number of calls per accident according to the time, the age, the number of serious cases etc."}
{"id": "PMID:7167", "title": "[Tracheal stenosis after tracheotomy. Apropos of 12 cases in 227 observations].", "content": "Out of 543 tracheotomized patients, 227 survived and 12 of them developed a tracheal stenosis syndrome (5,28 p. 100) including: 3 supra-ostial stenosis, 1 ostial and supra-ostial stenosis, 1 ostial stenosis, 3 intermediate stenosis and 4 distal stenosis. In two cases, the stenosis was found out during the removal of the cannula and in the other cases from 3 days to 8 months after the decannulation. The deffered treatment consisted in an anti-inflammatory medical treatment treatment (one case), in a permanent dilation with an Albouker tube (two cases), and in a resection of the stenosed tracheal part plus an anastomosis. Good results were obtained in 9 cases including the recovery of a satisfactory tracheal diameter. Because of a recurrence of the stenosis after resection and anastomosis, it was necessary, in two cases, to resort to another resection and, upon another occasion, to place a permanent cannulation. Finally, in one case, 2 Rethi operations were necessary to get a sub-normal tracheal diameter. From these facts, it emerges that tracheal stenosis are less important if, during the tracheotomy, a partial resection of the tracheal wall is effected (rather than an inverted U flap folded back at the bottom) together with the putting in of a cannula equipped with an elongated cylindrical cuff requiring a less important filing-up pressure (although just as efficient as far as tightness is concerned).", "contents": "[Tracheal stenosis after tracheotomy. Apropos of 12 cases in 227 observations]. Out of 543 tracheotomized patients, 227 survived and 12 of them developed a tracheal stenosis syndrome (5,28 p. 100) including: 3 supra-ostial stenosis, 1 ostial and supra-ostial stenosis, 1 ostial stenosis, 3 intermediate stenosis and 4 distal stenosis. In two cases, the stenosis was found out during the removal of the cannula and in the other cases from 3 days to 8 months after the decannulation. The deffered treatment consisted in an anti-inflammatory medical treatment treatment (one case), in a permanent dilation with an Albouker tube (two cases), and in a resection of the stenosed tracheal part plus an anastomosis. Good results were obtained in 9 cases including the recovery of a satisfactory tracheal diameter. Because of a recurrence of the stenosis after resection and anastomosis, it was necessary, in two cases, to resort to another resection and, upon another occasion, to place a permanent cannulation. Finally, in one case, 2 Rethi operations were necessary to get a sub-normal tracheal diameter. From these facts, it emerges that tracheal stenosis are less important if, during the tracheotomy, a partial resection of the tracheal wall is effected (rather than an inverted U flap folded back at the bottom) together with the putting in of a cannula equipped with an elongated cylindrical cuff requiring a less important filing-up pressure (although just as efficient as far as tightness is concerned)."}
{"id": "PMID:7171", "title": "Sympathoadrenal Neurochemistry and early weaning of swine.", "content": "Three litters of pigs were weaned at 21 days of age, and 3 others were left with the sow. Pigs were killed at 21, 23, 28, or 39 days of age. Weaned pigs exhibited anxiety, gastrointestinal dysfunction, and decreased rate of body weight gain. Plasma glucose or liver glycogen concentrations were not decreased by weaning. Adrenal gland weights and tyrosine hydroxylase (EC 1.14.3a), dopamine beta-hydroxylase (EC 1.14.2.1), phenethanolamine-N-methyl transferase (EC 2.1.1), and monoamine oxidase (EC 1.4.3.4) activities were increased after weaning. Adrenal catecholamine and cortisol levels and dopa decarboxylase (EC 4.1.1.26) and catechol-o-methyl transferase (EC 2.1.1.6) activities were not significantly altered, although some increases were indicated. Cranial cervical ganglionic choline acetyltransferase (EC 2.3.1.6) and tyrosine hydroxylase activities were increased after weaning. Weaning of swine at 21 days of age is a stressful experience, and many effects persist for at least 18 days; however, growth was no longer impaired 18 days after weaning.", "contents": "Sympathoadrenal Neurochemistry and early weaning of swine. Three litters of pigs were weaned at 21 days of age, and 3 others were left with the sow. Pigs were killed at 21, 23, 28, or 39 days of age. Weaned pigs exhibited anxiety, gastrointestinal dysfunction, and decreased rate of body weight gain. Plasma glucose or liver glycogen concentrations were not decreased by weaning. Adrenal gland weights and tyrosine hydroxylase (EC 1.14.3a), dopamine beta-hydroxylase (EC 1.14.2.1), phenethanolamine-N-methyl transferase (EC 2.1.1), and monoamine oxidase (EC 1.4.3.4) activities were increased after weaning. Adrenal catecholamine and cortisol levels and dopa decarboxylase (EC 4.1.1.26) and catechol-o-methyl transferase (EC 2.1.1.6) activities were not significantly altered, although some increases were indicated. Cranial cervical ganglionic choline acetyltransferase (EC 2.3.1.6) and tyrosine hydroxylase activities were increased after weaning. Weaning of swine at 21 days of age is a stressful experience, and many effects persist for at least 18 days; however, growth was no longer impaired 18 days after weaning."}
{"id": "PMID:7172", "title": "The source of a minor alpha 1-antitrypsin in variant serum.", "content": "An antiserum produced against human alpha1-antitrypsin gave 2 precipitin lines by immunodiffusion when tested against sera displaying MZ or MS phenotypes. Only one line (major antigen) was seen with sera displaying M phenotype, but a second line (minor antigen) became evident when the serum was concentrated 5-fold. The minor antigen appeared to be a denatured form of alpha1-antitrypsin, because the major antigen was converted to the minor one when purified alpha1-antitrypsin was incubated between pH 2.95 and 4.0. Such incubation inactivated the protein irreversibly. The purified protein was also inactivated completely within 1 hour at pH 4.95, but the activity was recovered completely by incubation for 2 to 4 hours at pH 8.0. The immunologic properties of the reactivated a1-antitrypsin were the same as those of the original untreated protein.", "contents": "The source of a minor alpha 1-antitrypsin in variant serum. An antiserum produced against human alpha1-antitrypsin gave 2 precipitin lines by immunodiffusion when tested against sera displaying MZ or MS phenotypes. Only one line (major antigen) was seen with sera displaying M phenotype, but a second line (minor antigen) became evident when the serum was concentrated 5-fold. The minor antigen appeared to be a denatured form of alpha1-antitrypsin, because the major antigen was converted to the minor one when purified alpha1-antitrypsin was incubated between pH 2.95 and 4.0. Such incubation inactivated the protein irreversibly. The purified protein was also inactivated completely within 1 hour at pH 4.95, but the activity was recovered completely by incubation for 2 to 4 hours at pH 8.0. The immunologic properties of the reactivated a1-antitrypsin were the same as those of the original untreated protein."}
{"id": "PMID:7173", "title": "Should fiberoptic bronchoscopy aspirates be cultured?", "content": "The reliability of fiberoptic bronchoscopy as a method to study the bacteriology of the lower respiratory tract was tested. The procedure used was suction aspiration through the inner channel after topical anesthesia with lidocaine. To detect contamination by oropharyngeal bacteria, the aspirates were cultured in patients with no evidence of active infection, comparison was made with results of transtracheal aspiration cultures, and the aspirate was tested for the presence of an oral dye marker. Results with all 3 methods of analysis indicated contamination with oropharyngeal bacteria that were presumably introduced during instrumentation through the upper airways. An additional factor studied was the effect of topical anesthetics. Analysis of aspirates showed that as much as 96 per cent of the specimen was anesthetic solution. Lidocaine also proved toxic to lower respiratory tract pathogens, although there were significant differences between bacterial species. It was concluded that fiberoptic bronchoscopy as performed in this study does not reliably reflect the bacteriology of the lower respiratory tract.", "contents": "Should fiberoptic bronchoscopy aspirates be cultured? The reliability of fiberoptic bronchoscopy as a method to study the bacteriology of the lower respiratory tract was tested. The procedure used was suction aspiration through the inner channel after topical anesthesia with lidocaine. To detect contamination by oropharyngeal bacteria, the aspirates were cultured in patients with no evidence of active infection, comparison was made with results of transtracheal aspiration cultures, and the aspirate was tested for the presence of an oral dye marker. Results with all 3 methods of analysis indicated contamination with oropharyngeal bacteria that were presumably introduced during instrumentation through the upper airways. An additional factor studied was the effect of topical anesthetics. Analysis of aspirates showed that as much as 96 per cent of the specimen was anesthetic solution. Lidocaine also proved toxic to lower respiratory tract pathogens, although there were significant differences between bacterial species. It was concluded that fiberoptic bronchoscopy as performed in this study does not reliably reflect the bacteriology of the lower respiratory tract."}
{"id": "PMID:7174", "title": "Spirometric comparison of carbuterol and isoproterenol aerosol therapy in bronchial asthma. A double blind, matched-pair study of 28 adults and a double blind crossover study of 18 children.", "content": "Two adrenergic aerosols were compared in a double blind, matched-pair study of 6 months' duration in 28 adult patients with chronic bronchial asthma, and in a double blind, crossover, short-term study in 18 children with severe asthma. In the adult study, one member of each pair was given either 150 mug of isoproterenol or 200 mug of carbuterol 4 times per day, by inhalation, for 6 months. In the childhood study, 18 children, 6 to 12 years of age, with moderate to severe asthma were studied in a double blind, crossover therapeutic trial in which high or low doses of aerosolized carbuterol or isoproterenol were given 4 times daily for 5 days each. Treatment results were evaluated by measuring forced vital capacity, 1-sec forced expiratory volume, and maximal mid-expiratory flow (FEF25-75%) at regulat intervals before and after administration of the respective test drugs. In the adult study, there was a significant difference between carbuterol and isoproterenol for forced vital capacity (P less than 0.02), for 1-sec forced expiratory volume (P less than 0.02), and for FEF25-75% (P less than 0.01) in favor of carbuterol. In the pediatric study, the difference between carbuterol and isoproterenol was significant (P less than 0.05) only for the FEF25-75% on the fifth day of treatment with the high dose administration of carbuterol. There was no associated toxicity of either drug with respect to electrocardiogram, blood chemistry, or subjective complaints. Tachyphylaxis (tolerance with time) to isoproterenol appeared to develop in one patient.", "contents": "Spirometric comparison of carbuterol and isoproterenol aerosol therapy in bronchial asthma. A double blind, matched-pair study of 28 adults and a double blind crossover study of 18 children. Two adrenergic aerosols were compared in a double blind, matched-pair study of 6 months' duration in 28 adult patients with chronic bronchial asthma, and in a double blind, crossover, short-term study in 18 children with severe asthma. In the adult study, one member of each pair was given either 150 mug of isoproterenol or 200 mug of carbuterol 4 times per day, by inhalation, for 6 months. In the childhood study, 18 children, 6 to 12 years of age, with moderate to severe asthma were studied in a double blind, crossover therapeutic trial in which high or low doses of aerosolized carbuterol or isoproterenol were given 4 times daily for 5 days each. Treatment results were evaluated by measuring forced vital capacity, 1-sec forced expiratory volume, and maximal mid-expiratory flow (FEF25-75%) at regulat intervals before and after administration of the respective test drugs. In the adult study, there was a significant difference between carbuterol and isoproterenol for forced vital capacity (P less than 0.02), for 1-sec forced expiratory volume (P less than 0.02), and for FEF25-75% (P less than 0.01) in favor of carbuterol. In the pediatric study, the difference between carbuterol and isoproterenol was significant (P less than 0.05) only for the FEF25-75% on the fifth day of treatment with the high dose administration of carbuterol. There was no associated toxicity of either drug with respect to electrocardiogram, blood chemistry, or subjective complaints. Tachyphylaxis (tolerance with time) to isoproterenol appeared to develop in one patient."}
{"id": "PMID:7178", "title": "Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol.", "content": "Twenty paid healthy students volunteered for a doubleblind cross-over trial on the effects of two weeks' treatment with placebo, thioridazine and bromazepam on psychomotor skills. The doses used were thioridazine 10 mg t.i.d. during the first week and 20 mg t.i.d. during the second week, or 6 mg of bromazepam t.i.d. during two weeks choice reaction test, two co-ordination tests, a divided attention test, flicker fusion, and proprioception tests were used. The psychomotor skills were measured in the afternoon of the 7th and 14th day of each treatment, 30, 90 and 150 minutes after the second daily administration of the drug in combination with either an alcoholic or a placebo drink. There were no significant differences between the test weeks. Thioridazine alone resembled placebo and had no major combined effect with alcohol. Bromazepam impaired reactive and co-ordinative skills and attention deteriorated. The combination of bromazepam and alcohol potentiated the deterious effects of the single agents, and this effect was most remarkable at 30 minutes. The subjects also gave exaggerated responses in the proprioceptive tests. No significant alterations were recorded in the flicker fusion frequency after any treatment.", "contents": "Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol. Twenty paid healthy students volunteered for a doubleblind cross-over trial on the effects of two weeks' treatment with placebo, thioridazine and bromazepam on psychomotor skills. The doses used were thioridazine 10 mg t.i.d. during the first week and 20 mg t.i.d. during the second week, or 6 mg of bromazepam t.i.d. during two weeks choice reaction test, two co-ordination tests, a divided attention test, flicker fusion, and proprioception tests were used. The psychomotor skills were measured in the afternoon of the 7th and 14th day of each treatment, 30, 90 and 150 minutes after the second daily administration of the drug in combination with either an alcoholic or a placebo drink. There were no significant differences between the test weeks. Thioridazine alone resembled placebo and had no major combined effect with alcohol. Bromazepam impaired reactive and co-ordinative skills and attention deteriorated. The combination of bromazepam and alcohol potentiated the deterious effects of the single agents, and this effect was most remarkable at 30 minutes. The subjects also gave exaggerated responses in the proprioceptive tests. No significant alterations were recorded in the flicker fusion frequency after any treatment."}
{"id": "PMID:7179", "title": "A new method using p-benzoquinone for coupling antigens and antibodies to marker substances.", "content": "A method using p-benzoquinone for coupling antigens and antibodies to enzymes and erythrocytes is described. The method involves the treatment of proteins (or polysaccharides) at pH 6 or 7 with an excess of p-benzoquinone. After removal of the unreacted reagent by gel filtration, the \"activated\" proteins were coupled at pH 8-9 with enzymes or erythrocytes. Biological activities of the proteins were not substantially modified by this treatment since 80-100% of the antigen binding capacity was found to be preserved in p-benzoquinone treated antibodies or Fab fragments. Anti-Ig antibodies (or Fab) were coupled by this procedure to peroxidase, alkaline phosphatase, lactoperoxidase, glucose oxidase and beta-galactosidase, and the conjugates obtained were found to be highly effective in detecting intracellular Ig by immunohistochemical techniques. Erythrocytes coated with sheep anti-mouse Ig antibody or Fab were used to titrate by passive hemagglutination serum Ig. The same erythrocytes were employed to detect by plaque assay mouse Ig secreting cells. Erythrocytes coated with peroxidase, alkaline phosphatase, bovine serum albumin, ribonuclease, Salmonella polysaccharide (B 27 +) and pneumoccocal polysaccharide SIII were employed to titrate serum antibody by passive hemagglutination and hemolysis and to detect mouse antibody secreting cells by plaque assay. All the antigens and antibodies coated erythrocytes prepared gave highly satisfactory and reproducible results.", "contents": "A new method using p-benzoquinone for coupling antigens and antibodies to marker substances. A method using p-benzoquinone for coupling antigens and antibodies to enzymes and erythrocytes is described. The method involves the treatment of proteins (or polysaccharides) at pH 6 or 7 with an excess of p-benzoquinone. After removal of the unreacted reagent by gel filtration, the \"activated\" proteins were coupled at pH 8-9 with enzymes or erythrocytes. Biological activities of the proteins were not substantially modified by this treatment since 80-100% of the antigen binding capacity was found to be preserved in p-benzoquinone treated antibodies or Fab fragments. Anti-Ig antibodies (or Fab) were coupled by this procedure to peroxidase, alkaline phosphatase, lactoperoxidase, glucose oxidase and beta-galactosidase, and the conjugates obtained were found to be highly effective in detecting intracellular Ig by immunohistochemical techniques. Erythrocytes coated with sheep anti-mouse Ig antibody or Fab were used to titrate by passive hemagglutination serum Ig. The same erythrocytes were employed to detect by plaque assay mouse Ig secreting cells. Erythrocytes coated with peroxidase, alkaline phosphatase, bovine serum albumin, ribonuclease, Salmonella polysaccharide (B 27 +) and pneumoccocal polysaccharide SIII were employed to titrate serum antibody by passive hemagglutination and hemolysis and to detect mouse antibody secreting cells by plaque assay. All the antigens and antibodies coated erythrocytes prepared gave highly satisfactory and reproducible results."}
{"id": "PMID:7187", "title": "[Ionization of the acid-base groups of polyene antibiotics in aqueous solutions].", "content": "The acid-base characteristics of polyenic antibiotics, such as nystatin, mycoheptin and levorin in aqueous solutions were studied. A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of vater-insoluble substances. The ionization constants of the carboxylic and amine groups of the antibiotics at several temperatures were determined. It was found that ionization of the acid group did not practically depend on the temperature. At the same time the heat effect of the amine group ionization was significant and amounted to about 10 kcal/mole. Thermodynamic analysis of the ionization process of the polyenic antibiotics in aqueous solutions was performed. Integral components defining the process energetics were calculated.", "contents": "[Ionization of the acid-base groups of polyene antibiotics in aqueous solutions]. The acid-base characteristics of polyenic antibiotics, such as nystatin, mycoheptin and levorin in aqueous solutions were studied. A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of vater-insoluble substances. The ionization constants of the carboxylic and amine groups of the antibiotics at several temperatures were determined. It was found that ionization of the acid group did not practically depend on the temperature. At the same time the heat effect of the amine group ionization was significant and amounted to about 10 kcal/mole. Thermodynamic analysis of the ionization process of the polyenic antibiotics in aqueous solutions was performed. Integral components defining the process energetics were calculated."}
{"id": "PMID:7188", "title": "Mechanism of action of miconazole: labilization of rat liver lysosomes in vitro by miconazole.", "content": "Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. Its labilizing effect is followed by measuring the release of lysosomal hydrolases, namely, acid phosphatase, beta-glucuronidase, and arylsulfatase A. The effect of miconazole is concentration dependent in the range of 10(-5) to 1.2 x 10(-4) M. However, at higher concentrations, miconazole inhibits enzyme release but does not inhibit enzyme activities per se. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. Membrane-active drugs such as nystatin, 2-phenethyl-alcohol, hexachlorophene, and digitonin have been compared with miconazole for their lysosome-labilizing action. The effect of miconazole on the lysosomal membrane is confirmed by a decrease in turbidity of the lysosomal suspension.", "contents": "Mechanism of action of miconazole: labilization of rat liver lysosomes in vitro by miconazole. Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. Its labilizing effect is followed by measuring the release of lysosomal hydrolases, namely, acid phosphatase, beta-glucuronidase, and arylsulfatase A. The effect of miconazole is concentration dependent in the range of 10(-5) to 1.2 x 10(-4) M. However, at higher concentrations, miconazole inhibits enzyme release but does not inhibit enzyme activities per se. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. Membrane-active drugs such as nystatin, 2-phenethyl-alcohol, hexachlorophene, and digitonin have been compared with miconazole for their lysosome-labilizing action. The effect of miconazole on the lysosomal membrane is confirmed by a decrease in turbidity of the lysosomal suspension."}
{"id": "PMID:7189", "title": "In vitro activity of josamycin against aerobic gram-positive cocci and anaerobes.", "content": "Josamycin, a new macrolide antibiotic, was compared with ampicillin, erythromycin, and clindamycin in vitro against 25 isolates each of pneumococci, enterococci, Staphylococcus aureus, S. epidermidis, and nonenterococcal hemolytic streptococci and against 25 anaerobes including 10 Bacteroides fragilis. Minimal inhibitory concentration and minimal bactericidal concentration data were obtained for the aerobic organisms, using serial twofold tube dilutions in Mueller-Hinton broth. Minimal inhibitory concentrations were determined for the anaerobes by the agar dilution technique. Josamycin was comparable to erythromycin and clindamycin in activity against the pneumococci, streptococci, and staphylococci and was more active than clindamycin against enterococci. It was somewhat less active than ampicillin against enterococci and S. epidermidis and showed its greatest in vitro activity against anaerobes, being comparable to clindamycin.", "contents": "In vitro activity of josamycin against aerobic gram-positive cocci and anaerobes. Josamycin, a new macrolide antibiotic, was compared with ampicillin, erythromycin, and clindamycin in vitro against 25 isolates each of pneumococci, enterococci, Staphylococcus aureus, S. epidermidis, and nonenterococcal hemolytic streptococci and against 25 anaerobes including 10 Bacteroides fragilis. Minimal inhibitory concentration and minimal bactericidal concentration data were obtained for the aerobic organisms, using serial twofold tube dilutions in Mueller-Hinton broth. Minimal inhibitory concentrations were determined for the anaerobes by the agar dilution technique. Josamycin was comparable to erythromycin and clindamycin in activity against the pneumococci, streptococci, and staphylococci and was more active than clindamycin against enterococci. It was somewhat less active than ampicillin against enterococci and S. epidermidis and showed its greatest in vitro activity against anaerobes, being comparable to clindamycin."}
{"id": "PMID:7190", "title": "Observations on brilliant green agar with H2S indicator.", "content": "Several formulations of brilliant green agar with an added H2S indicator were evaluated. Results were optimum with variations of a basic formula consisting of 40 g of tryptic soy agar (Difco), 8 g of lactose, 8 g of sucrose, 80 mg of phenol red, 1 g of sulfanilamide, 1.5 g of ferric ammonium citrate, 5 g of sodium thiosulfate pentahydrate, and 7 mg of brilliant green dye per liter. Brilliant green dye was added after sterilization of the other components This formulation supported good growth of all of 39 strains of Salmonella tested. Normal biochemical types formed pink colonies with black centers, and an H2S-negative S. choleraesuis formed pink colonies without black centers. Of other bacteria tested, only Enterobacter, Klebsiella, and a few Citrobacter strains showed significant growth in 24 h. When lactose was omitted from the formulation, a lactose-fermenting strain formed pink colonies with black centers, and differentiation of Salmonella from the Enterobacter-Klebsiella groups was equally good. Addition of xylose (4.0 g) and L-lysine hydrochloride (5.4 g) to the above formulation improved differentiation between Salmonella and the few Citrobacter strains that grew and produced more intense blackening in Salmonella colonies. Addition of an H2S indicator to brilliant green agar formulations aided in identification of Salmonella colonies, especially in mixtures with other bacteria. These media were judged to give better differentiation of salmonellae from other bacteria than Hektoen agar with added novobiocin (10 mg/liter).", "contents": "Observations on brilliant green agar with H2S indicator. Several formulations of brilliant green agar with an added H2S indicator were evaluated. Results were optimum with variations of a basic formula consisting of 40 g of tryptic soy agar (Difco), 8 g of lactose, 8 g of sucrose, 80 mg of phenol red, 1 g of sulfanilamide, 1.5 g of ferric ammonium citrate, 5 g of sodium thiosulfate pentahydrate, and 7 mg of brilliant green dye per liter. Brilliant green dye was added after sterilization of the other components This formulation supported good growth of all of 39 strains of Salmonella tested. Normal biochemical types formed pink colonies with black centers, and an H2S-negative S. choleraesuis formed pink colonies without black centers. Of other bacteria tested, only Enterobacter, Klebsiella, and a few Citrobacter strains showed significant growth in 24 h. When lactose was omitted from the formulation, a lactose-fermenting strain formed pink colonies with black centers, and differentiation of Salmonella from the Enterobacter-Klebsiella groups was equally good. Addition of xylose (4.0 g) and L-lysine hydrochloride (5.4 g) to the above formulation improved differentiation between Salmonella and the few Citrobacter strains that grew and produced more intense blackening in Salmonella colonies. Addition of an H2S indicator to brilliant green agar formulations aided in identification of Salmonella colonies, especially in mixtures with other bacteria. These media were judged to give better differentiation of salmonellae from other bacteria than Hektoen agar with added novobiocin (10 mg/liter)."}
{"id": "PMID:7191", "title": "Microbial formation and degradation of dimethylamine.", "content": "Dimethylamine was formed from trimethylamine in soils of different pH values. The rate of disappearance of the secondary amine from soil was affected by pH and was markedly reduced under anaerobiosis. The accumulation of dimethylamine in cultures of Micrococcus sp. provided with trimethylamine depended on the nitrogen sources available to the bacterium but was not greatly influenced by the C-N ratio of the medium. Dimethylamine and nitrite accumulated in large amounts at pH 6.0 to 8.0 in cultures containing the tertiary amine and nitrate, but dimethylnitrosamine was apparently not produced.", "contents": "Microbial formation and degradation of dimethylamine. Dimethylamine was formed from trimethylamine in soils of different pH values. The rate of disappearance of the secondary amine from soil was affected by pH and was markedly reduced under anaerobiosis. The accumulation of dimethylamine in cultures of Micrococcus sp. provided with trimethylamine depended on the nitrogen sources available to the bacterium but was not greatly influenced by the C-N ratio of the medium. Dimethylamine and nitrite accumulated in large amounts at pH 6.0 to 8.0 in cultures containing the tertiary amine and nitrate, but dimethylnitrosamine was apparently not produced."}
{"id": "PMID:7192", "title": "Toxicity of ammonia to algae in sewage oxidation ponds.", "content": "Ammonia, at concentrations over 2.0 mM and at pH values over 8.0, inhibits photosynthesis and growth of Scenedesmus obliquus, a dominant species in high-rate sewage oxidation ponds. Photosynthesis of Chlorella pyrenoidosa, Anacystis nidulans, and Plectonema boryanum is also susceptible to ammonia inhibition. Dark respiration and cell morphology were unaffected by any combination of pH and ammonia concentrations tested, thus limiting the apparent effect to inhibition of the normal function of the chloroplasts. Methylamine had the same effect as ammonia, and its penetration into the cells was found to be pH dependent. Therefore, the dependence of toxicity of amines to algae on pH apparently results from the inability to penetrate the cell membrane in the ionized form. When operated at 120-h detention time of raw wastewater, the high-rate oxidation pond maintained a steady state with respect to algal growth and oxygen concentration, and the concentration of ammonia did not exceed 1.0 mM. Shifting the pond to 48-h detention time caused an increase in ammonia concentration in the pond water to 2.5 mM, and the pond gradually turned anaerobic. Photosynthesis, which usually elevates the pH of the pond water to 9.0 to 10.0, could not proceed beyond pH 7.9 because of the high concentration of ammonia, and the algal population was washed out and reduced to a concentration that could maintain a doubling time of 48 h without photosynthesis bringing the pH to inhibitory levels. Under these conditions, the pH of the bond becomes a factor that limits the operational efficiency of the oxidation pond.", "contents": "Toxicity of ammonia to algae in sewage oxidation ponds. Ammonia, at concentrations over 2.0 mM and at pH values over 8.0, inhibits photosynthesis and growth of Scenedesmus obliquus, a dominant species in high-rate sewage oxidation ponds. Photosynthesis of Chlorella pyrenoidosa, Anacystis nidulans, and Plectonema boryanum is also susceptible to ammonia inhibition. Dark respiration and cell morphology were unaffected by any combination of pH and ammonia concentrations tested, thus limiting the apparent effect to inhibition of the normal function of the chloroplasts. Methylamine had the same effect as ammonia, and its penetration into the cells was found to be pH dependent. Therefore, the dependence of toxicity of amines to algae on pH apparently results from the inability to penetrate the cell membrane in the ionized form. When operated at 120-h detention time of raw wastewater, the high-rate oxidation pond maintained a steady state with respect to algal growth and oxygen concentration, and the concentration of ammonia did not exceed 1.0 mM. Shifting the pond to 48-h detention time caused an increase in ammonia concentration in the pond water to 2.5 mM, and the pond gradually turned anaerobic. Photosynthesis, which usually elevates the pH of the pond water to 9.0 to 10.0, could not proceed beyond pH 7.9 because of the high concentration of ammonia, and the algal population was washed out and reduced to a concentration that could maintain a doubling time of 48 h without photosynthesis bringing the pH to inhibitory levels. Under these conditions, the pH of the bond becomes a factor that limits the operational efficiency of the oxidation pond."}
{"id": "PMID:7193", "title": "Production of extracellular alpha-glucosidase by a thermophilic Bacillus species.", "content": "Production of extracellular alpha-glucosidase was studied with strain KP 1006 of a new species of thermophilic Bacillus, which was isolated from soil samples by enrichment at 65 C. alpha-Glucosidase production was maximum at 60 C and at an initial pH of 6.5. The final enzyme yield was increased by starch, maltose, glycerol, peptone, and yeast extract but reduced by acetate and gluconate, alpha-Glucosidase was formed in the cytoplasm and accumulated as a large pool during the logarithmic growth phase. At a midpoint of this period, the enzyme appeared in the culture broth, and its level increased until the end of the stationary phase.", "contents": "Production of extracellular alpha-glucosidase by a thermophilic Bacillus species. Production of extracellular alpha-glucosidase was studied with strain KP 1006 of a new species of thermophilic Bacillus, which was isolated from soil samples by enrichment at 65 C. alpha-Glucosidase production was maximum at 60 C and at an initial pH of 6.5. The final enzyme yield was increased by starch, maltose, glycerol, peptone, and yeast extract but reduced by acetate and gluconate, alpha-Glucosidase was formed in the cytoplasm and accumulated as a large pool during the logarithmic growth phase. At a midpoint of this period, the enzyme appeared in the culture broth, and its level increased until the end of the stationary phase."}
{"id": "PMID:7194", "title": "Factors influencing the production of cellulases by Sporotrichum thermophile.", "content": "Cellulase production and growth of a strain of Sporotrichum thermophile were studied by using a mineral salts medium supplemented with yeast extract and insoluble cellulose. The effects of cultural conditions, such as pH, nitrogen source, substrate concentration, and temperature, were examined. Maximum production of C1 and CX cellulases occurred at 45 C in 2 to 4 days, in the presence of 1% Solka/Floc as substrate, when NaNO3 or urea used as sources of nitrogen. Under these conditions, cellulolytic activity of culture filtrates appeared to be similar to that reported for Trichoderma viride grown in a favorable environment. However, comparable yields of cellulase were produced by S. thermophile in less than one-quarter the time required by mesophilic fungi.", "contents": "Factors influencing the production of cellulases by Sporotrichum thermophile. Cellulase production and growth of a strain of Sporotrichum thermophile were studied by using a mineral salts medium supplemented with yeast extract and insoluble cellulose. The effects of cultural conditions, such as pH, nitrogen source, substrate concentration, and temperature, were examined. Maximum production of C1 and CX cellulases occurred at 45 C in 2 to 4 days, in the presence of 1% Solka/Floc as substrate, when NaNO3 or urea used as sources of nitrogen. Under these conditions, cellulolytic activity of culture filtrates appeared to be similar to that reported for Trichoderma viride grown in a favorable environment. However, comparable yields of cellulase were produced by S. thermophile in less than one-quarter the time required by mesophilic fungi."}
{"id": "PMID:7195", "title": "Degradation of [8,9,-14C]endosulfan by soil microorganisms.", "content": "Twenty-eight soil fungi, 49 soil bacteria, and 10 actinomycetes were tested as to their ability to degrade the insecticide endosulfan. Using 14C-labeled material, the qualitative as well as the quantitative formation of metabolities, as well as of 14CO2, could be followed. Sixteen fungi, 15 bacteria, and 3 actinomycetes were found capable of metabolizing more than 30% of the applied endosulfan. The major metabolities detected were endosulfate, formed by oxidation of the sulfite group, and endodiol, formed by hydrolysis of the ester bond. The majority of highly active fungi formed endosulfate as the major metabolite, whereas the majority of active bacteria formed endodiol. In addition to endosulfate and endodiol, individual cultures contained small quantities of endohydroxyether and two unidentified products. The very small quantities of 14CO2 evolved from cultures indicated that an extensive mineralization of the carbon skeleton of endosulfan did not occur.", "contents": "Degradation of [8,9,-14C]endosulfan by soil microorganisms. Twenty-eight soil fungi, 49 soil bacteria, and 10 actinomycetes were tested as to their ability to degrade the insecticide endosulfan. Using 14C-labeled material, the qualitative as well as the quantitative formation of metabolities, as well as of 14CO2, could be followed. Sixteen fungi, 15 bacteria, and 3 actinomycetes were found capable of metabolizing more than 30% of the applied endosulfan. The major metabolities detected were endosulfate, formed by oxidation of the sulfite group, and endodiol, formed by hydrolysis of the ester bond. The majority of highly active fungi formed endosulfate as the major metabolite, whereas the majority of active bacteria formed endodiol. In addition to endosulfate and endodiol, individual cultures contained small quantities of endohydroxyether and two unidentified products. The very small quantities of 14CO2 evolved from cultures indicated that an extensive mineralization of the carbon skeleton of endosulfan did not occur."}
{"id": "PMID:7196", "title": "Stabilization of a psychrotrophic Pseudomonas protease by calcium against thermal inactivation in milk at ultrahigh temperature.", "content": "The heat-stable extracellular protease of Pseudomonas sp. (isolate MC60) was investigated. Heat resistance of the enzyme in milk at sterilization temperature was dependent on the presence of Ca2+. The half-life of the enzyme at ultrahigh temperature (149 C) in skim milk or milk-salts buffer with Ca2+ was approximately 7.0 s. Treatment of milk with chelators completely removed the heatstabilizing effect of milk. The enzyme was partially purified by ammonium sulfate precipitation and column chromatography on Sephadex G-100. At 21 C the enzyme retained greater than 85% activity after exposure to pH values between 5 and 10. Enzyme activity was reduced by metal chelating agents. Both Ca2+ and Zn2+ were required for optimal enzyme activity. Molecular weight was estimated at 48,000 by gel filtration.", "contents": "Stabilization of a psychrotrophic Pseudomonas protease by calcium against thermal inactivation in milk at ultrahigh temperature. The heat-stable extracellular protease of Pseudomonas sp. (isolate MC60) was investigated. Heat resistance of the enzyme in milk at sterilization temperature was dependent on the presence of Ca2+. The half-life of the enzyme at ultrahigh temperature (149 C) in skim milk or milk-salts buffer with Ca2+ was approximately 7.0 s. Treatment of milk with chelators completely removed the heatstabilizing effect of milk. The enzyme was partially purified by ammonium sulfate precipitation and column chromatography on Sephadex G-100. At 21 C the enzyme retained greater than 85% activity after exposure to pH values between 5 and 10. Enzyme activity was reduced by metal chelating agents. Both Ca2+ and Zn2+ were required for optimal enzyme activity. Molecular weight was estimated at 48,000 by gel filtration."}
{"id": "PMID:7197", "title": "N-Nitrosamine formation by cultures of several microorganisms.", "content": "Of 38 pure cultures of microorganisms tested, only one, Pseudomonas stutzeri, was capable of forming dimethylnitrosamine from dimethylamine and nitrite during growth. Resting cells of P. stutzeri, Cryptococcus terreus, Escherichia coli, and Xanthomonas campestris formed dimethylnitrosamine, although no nitrosamine was found in growing cultures of the latter three organisms. No nitrosamine was produced by either growing cultures or resting-cell suspensions of Pseudomonas fragi or Proteus mirabilis. Boiled cells of P. stutzeri, but not those of C. terreus, E. coli, and X. campestris, formed dimethylnitrosamine, and this nitrosamine was also produced by extracts of E. coli cells at pH 5.0.", "contents": "N-Nitrosamine formation by cultures of several microorganisms. Of 38 pure cultures of microorganisms tested, only one, Pseudomonas stutzeri, was capable of forming dimethylnitrosamine from dimethylamine and nitrite during growth. Resting cells of P. stutzeri, Cryptococcus terreus, Escherichia coli, and Xanthomonas campestris formed dimethylnitrosamine, although no nitrosamine was found in growing cultures of the latter three organisms. No nitrosamine was produced by either growing cultures or resting-cell suspensions of Pseudomonas fragi or Proteus mirabilis. Boiled cells of P. stutzeri, but not those of C. terreus, E. coli, and X. campestris, formed dimethylnitrosamine, and this nitrosamine was also produced by extracts of E. coli cells at pH 5.0."}
{"id": "PMID:7198", "title": "Influence of sewage discharge on nitrogen fixation and nitrogen flux from coral reefs in Kaneohe Bay, Hawaii.", "content": "Nitrogen fixation was investigated in Kaneohe Bay, Oahu, Hawaii, a subtropical eutrophic estuary, by using the acetylene reduction technique on algal samples. No active, planktonic, N2-fixing blue-green algae or bacteria were observed. However, Calothrix and Nostoc capable of fixing N2 were cultured from navigational buoys and dead coral heads. Nitrogen fixation associated with these structures was greater in the middle sector than in the south and north sectors of the estuary. Experiments demonstrated that the fixation was photosynthetically dependent. Examination of the data showed that there was no significant correlation between rates of nitrogen fixation and concentration of combined nitrogen compounds in the Bay water. Fixation was significantly correlated to the inorganic N/P (atomic) ratio in the south and middle sectors but not in the north sector. The nutrient data indicate there was a flux of combined nitrogen, but not phosphate, from the reef flats.", "contents": "Influence of sewage discharge on nitrogen fixation and nitrogen flux from coral reefs in Kaneohe Bay, Hawaii. Nitrogen fixation was investigated in Kaneohe Bay, Oahu, Hawaii, a subtropical eutrophic estuary, by using the acetylene reduction technique on algal samples. No active, planktonic, N2-fixing blue-green algae or bacteria were observed. However, Calothrix and Nostoc capable of fixing N2 were cultured from navigational buoys and dead coral heads. Nitrogen fixation associated with these structures was greater in the middle sector than in the south and north sectors of the estuary. Experiments demonstrated that the fixation was photosynthetically dependent. Examination of the data showed that there was no significant correlation between rates of nitrogen fixation and concentration of combined nitrogen compounds in the Bay water. Fixation was significantly correlated to the inorganic N/P (atomic) ratio in the south and middle sectors but not in the north sector. The nutrient data indicate there was a flux of combined nitrogen, but not phosphate, from the reef flats."}
{"id": "PMID:7199", "title": "Cultivation of mycoplasmas in a modified tissue culture medium.", "content": "A new medium, which contained a chemically defined tissue culture base (\"medium 199\"), was developed for the cultivation of mycoplasmas. When supplemented with albumin, glucose, serum, and yeast extract, the new medium adequately supported the growth of Mycoplasma and Acholeplasma species.", "contents": "Cultivation of mycoplasmas in a modified tissue culture medium. A new medium, which contained a chemically defined tissue culture base (\"medium 199\"), was developed for the cultivation of mycoplasmas. When supplemented with albumin, glucose, serum, and yeast extract, the new medium adequately supported the growth of Mycoplasma and Acholeplasma species."}
{"id": "PMID:7215", "title": "Further evidence for the transmission of Mansonella ozzardi by Simulium amazonicum in Brazil.", "content": "The transmission of Mansonella ozzardi was studied in two rubber collecting villages on the River Purus, state of Amazonas, Brazil. Haematophagous insects were collected from human and bovine baits during the day and night: 687 Mansonia amazonensis and 154 Culicoides sp. indet. were free from infection with M. ozzardi. The former species is probably not a vector, but the low numbers of culicoides dissected preclude any determination of its vector status. Thirty-five (0-99%) of 3530 Simulium amazonicum dissected were found naturally infected with larvae of M. ozzardi. Two hundred and ninety-nine M. amazonensis and 280 S. amazonicum were experimentally infected with M. ozzardi by feeding on volunteers. Microfilariae were detected in the blood meals of both species but no developing larvae were found in the thoracic muscles of M. amazonensis, confirming its non-vector status; 7-1% of the S. amazonicum dissected had filarial larvae in the thorax. There was a statistically significant difference between this rate and the natural rate of infection in this region, verifying that penetration of the thoraric muscles by M. ozzardi had occurred in the experimental infection. The data confirm the observation of Cerqueira (1959) that S. amazonicum transmits M. ozzardi in Brazil.", "contents": "Further evidence for the transmission of Mansonella ozzardi by Simulium amazonicum in Brazil. The transmission of Mansonella ozzardi was studied in two rubber collecting villages on the River Purus, state of Amazonas, Brazil. Haematophagous insects were collected from human and bovine baits during the day and night: 687 Mansonia amazonensis and 154 Culicoides sp. indet. were free from infection with M. ozzardi. The former species is probably not a vector, but the low numbers of culicoides dissected preclude any determination of its vector status. Thirty-five (0-99%) of 3530 Simulium amazonicum dissected were found naturally infected with larvae of M. ozzardi. Two hundred and ninety-nine M. amazonensis and 280 S. amazonicum were experimentally infected with M. ozzardi by feeding on volunteers. Microfilariae were detected in the blood meals of both species but no developing larvae were found in the thoracic muscles of M. amazonensis, confirming its non-vector status; 7-1% of the S. amazonicum dissected had filarial larvae in the thorax. There was a statistically significant difference between this rate and the natural rate of infection in this region, verifying that penetration of the thoraric muscles by M. ozzardi had occurred in the experimental infection. The data confirm the observation of Cerqueira (1959) that S. amazonicum transmits M. ozzardi in Brazil."}
{"id": "PMID:7216", "title": "[Studies on the properties of acid erythrocyte phosphatase in sheep and the isoenzymes of sheep and goat acid erythrocyte phosphatase].", "content": "Ovine erythrocytic acid phosphatase showed two peaks of activity at pH 5.0 and 5.7 in acetate buffer with p-nitrophenylphosphate as substrate. The enzyme was only slightly inhibited by fluoride and L-phenylalanine, but high concentrations of urea strongly inhibited it. Activity of the enzyme was greater in goat erythrocytes than in sheep. By means of starch electrophoresis, three isoenzymes belonging to nine types were separated from the ovine enzymes, while three isoenzymes of five types were present in goats. Electrophoresis in polyacrylamide gel was suitable for detecting the rapidly migrating isoenzymes.", "contents": "[Studies on the properties of acid erythrocyte phosphatase in sheep and the isoenzymes of sheep and goat acid erythrocyte phosphatase]. Ovine erythrocytic acid phosphatase showed two peaks of activity at pH 5.0 and 5.7 in acetate buffer with p-nitrophenylphosphate as substrate. The enzyme was only slightly inhibited by fluoride and L-phenylalanine, but high concentrations of urea strongly inhibited it. Activity of the enzyme was greater in goat erythrocytes than in sheep. By means of starch electrophoresis, three isoenzymes belonging to nine types were separated from the ovine enzymes, while three isoenzymes of five types were present in goats. Electrophoresis in polyacrylamide gel was suitable for detecting the rapidly migrating isoenzymes."}
{"id": "PMID:7218", "title": "[Origination and importance of glycolysis for malignomas and utilization of this property in the chemotherapy of cancer (author's transl)].", "content": "Glycolysis is not of importance for the process of carcinogenesis. It is very likely, however, that certain molecular-biological and genetic changes are produced which enable the malignant cell to develop an intensive glycolysis, for instance, to form specialized glycolytic isoenzymes already during oncogenesis, and may possible become effective in the primary tumour. As soon as the capacity of the cancer cell to intensive aerobic and anaerobic glycolysis has become manifest, this process is an irreversible one. The extent of glycolysis of a malignoma is greatly dependent on the degree of its dedifferentiation and vascularization (glucose supply), although a direct correlation between growth and the amount of lactic acid formed does not seem to exist. However, a certain utilization of glucose is essential for cell proliferation (supply of basic substances). In many cases there is a correlation between the extent of glycolysis measurable under optimal conditions in vitro (glycolytic power) in a malignant tumour and its growth rate recognizable in vivo. The formation of a strong capacity for glucose degradation via the Embden-Meyerhof pathway that cannot be fully utilized by the whole tumour in vivo is first of all designed to ensure survival and proliferation of cells even at extremely low levels of glucose supply. This process can be regarded as an adaptation of cancer cells to a situation of unsufficient supply. This circumstance endows the cancer cell with an essential advantage over the normal cell which enables or even promotes its invasive and destructive growth and metastatic dissemination. In this respect they differ, for instance, from benignant neoplasms. The possibility is discussed to control neoplastic growth by adjusting an optimal pH difference between normal and tumour tissue by combined administration of detoxicated drugs which are converted to their toxic forms only in the tumour by means of strongly pH-dependent exogenous enzymes.", "contents": "[Origination and importance of glycolysis for malignomas and utilization of this property in the chemotherapy of cancer (author's transl)]. Glycolysis is not of importance for the process of carcinogenesis. It is very likely, however, that certain molecular-biological and genetic changes are produced which enable the malignant cell to develop an intensive glycolysis, for instance, to form specialized glycolytic isoenzymes already during oncogenesis, and may possible become effective in the primary tumour. As soon as the capacity of the cancer cell to intensive aerobic and anaerobic glycolysis has become manifest, this process is an irreversible one. The extent of glycolysis of a malignoma is greatly dependent on the degree of its dedifferentiation and vascularization (glucose supply), although a direct correlation between growth and the amount of lactic acid formed does not seem to exist. However, a certain utilization of glucose is essential for cell proliferation (supply of basic substances). In many cases there is a correlation between the extent of glycolysis measurable under optimal conditions in vitro (glycolytic power) in a malignant tumour and its growth rate recognizable in vivo. The formation of a strong capacity for glucose degradation via the Embden-Meyerhof pathway that cannot be fully utilized by the whole tumour in vivo is first of all designed to ensure survival and proliferation of cells even at extremely low levels of glucose supply. This process can be regarded as an adaptation of cancer cells to a situation of unsufficient supply. This circumstance endows the cancer cell with an essential advantage over the normal cell which enables or even promotes its invasive and destructive growth and metastatic dissemination. In this respect they differ, for instance, from benignant neoplasms. The possibility is discussed to control neoplastic growth by adjusting an optimal pH difference between normal and tumour tissue by combined administration of detoxicated drugs which are converted to their toxic forms only in the tumour by means of strongly pH-dependent exogenous enzymes."}
{"id": "PMID:7219", "title": "[The influence of role induction on the success of systematic desensitization of socially anxious students (author's transl)].", "content": "The so-called nonspecific factors involved in therapy have received little attention up to the present - namely, that of role induction (preparing the clients for treatment by informing them about the rationale of treatment, the treatment process, and their part in therapy). For this reason, we constructed an induction text for systematic desensitization according to the principles of instructional psychology (Ausubel), and proceeded to test it for understandability and therapeutic effectiveness. With control group design which assured the realization of the independent variable of role induction, the effective results of desensitization with role induction were compared both with those of simple desensitization and those of a waiting control group. The resultant differences in the group with role induction indicate the additional advantages of this technique for therapy. Essentially, role induction seems to manifest itself in terms of a contribution to more active, independent role formation on the part of the client.", "contents": "[The influence of role induction on the success of systematic desensitization of socially anxious students (author's transl)]. The so-called nonspecific factors involved in therapy have received little attention up to the present - namely, that of role induction (preparing the clients for treatment by informing them about the rationale of treatment, the treatment process, and their part in therapy). For this reason, we constructed an induction text for systematic desensitization according to the principles of instructional psychology (Ausubel), and proceeded to test it for understandability and therapeutic effectiveness. With control group design which assured the realization of the independent variable of role induction, the effective results of desensitization with role induction were compared both with those of simple desensitization and those of a waiting control group. The resultant differences in the group with role induction indicate the additional advantages of this technique for therapy. Essentially, role induction seems to manifest itself in terms of a contribution to more active, independent role formation on the part of the client."}
{"id": "PMID:7220", "title": "Cell populations in a renal lesion produced by local injection of xenogeneic spleen cells in cyclophosphamide-treated rats.", "content": "The frequency and distribution of donor and host lymphoid cells in different stages of a lesion produced by injecting mouse spleen cells beneath the renal capsules of rats treated 24 h previously with cyclophosphamide have been studied by immunofluorescent staining with species-specific anti-lymphocyte sera. Donor cells were predominant in the early stages of the reaction and penetrated the outer part of the renal cortex, but by day 7 when the lesion reached its maximum extent most of the infiltrating cells were of host origin. Donor cells never extended deeply into the kidney and they were not uniformly intermingled with the main mass of host cells but their presence seemed to be necessary for the maintenance of the reaction, since it began to decline when donor cells were no longer detectable in the injected kidney.", "contents": "Cell populations in a renal lesion produced by local injection of xenogeneic spleen cells in cyclophosphamide-treated rats. The frequency and distribution of donor and host lymphoid cells in different stages of a lesion produced by injecting mouse spleen cells beneath the renal capsules of rats treated 24 h previously with cyclophosphamide have been studied by immunofluorescent staining with species-specific anti-lymphocyte sera. Donor cells were predominant in the early stages of the reaction and penetrated the outer part of the renal cortex, but by day 7 when the lesion reached its maximum extent most of the infiltrating cells were of host origin. Donor cells never extended deeply into the kidney and they were not uniformly intermingled with the main mass of host cells but their presence seemed to be necessary for the maintenance of the reaction, since it began to decline when donor cells were no longer detectable in the injected kidney."}
{"id": "PMID:7221", "title": "Facilitation of the growth of an allogeneic tumour by suppressor cells in newborn rats.", "content": "The intravenous injection of as few as 15 Walker tumour cells into newborn rats consistently resulted in the development of pulmonary metastases and the death of the recipient within 2 weeks. Neither the outcome of tumour cell injection nor the interval until death could be modified by transferring 2 x 10(7) lymphocytes from tumour-immune adult rats to the neonataal hosts. In contrast with this failure to transfer adoptive anti-tumour immune responses to intact recipients, the administration of 350 rad irradiation before transfer of 10(6) immune lymphocytes constantly afforded protection against inoculated tumour cells. The simultaneous transfer of neonatal thymus cells with immune lymphocytes interfered with the establishment of an adoptive response in the irradiated newborn. Intiation of a graft-versus-host response in F1 hybrid neonates by injecting parental strain lymphocytes conferred resistance to tumour growth of the recpient, the magnitude of this effect increasing with the strength of the graft-versus-host reaction.", "contents": "Facilitation of the growth of an allogeneic tumour by suppressor cells in newborn rats. The intravenous injection of as few as 15 Walker tumour cells into newborn rats consistently resulted in the development of pulmonary metastases and the death of the recipient within 2 weeks. Neither the outcome of tumour cell injection nor the interval until death could be modified by transferring 2 x 10(7) lymphocytes from tumour-immune adult rats to the neonataal hosts. In contrast with this failure to transfer adoptive anti-tumour immune responses to intact recipients, the administration of 350 rad irradiation before transfer of 10(6) immune lymphocytes constantly afforded protection against inoculated tumour cells. The simultaneous transfer of neonatal thymus cells with immune lymphocytes interfered with the establishment of an adoptive response in the irradiated newborn. Intiation of a graft-versus-host response in F1 hybrid neonates by injecting parental strain lymphocytes conferred resistance to tumour growth of the recpient, the magnitude of this effect increasing with the strength of the graft-versus-host reaction."}
{"id": "PMID:7222", "title": "Suppressor cells in homograft tolerant rats.", "content": "If sufficient normal syngeneic lymphocytes to effect skin graft rejection are transferred to homograft tolerant rats, a prolonged period elapses before lymphoid cells from the recipient acquire normal levels of GvH responsiveness against tissues of which the donor was previously tolerant (Silvers and Billingham, 1970; Elkins, 1972; Miyamoto and McCullagh, 1974). Although the ability of lymphoid populations of such animals to mount GvH reactions can be demonstrated to reside in donor type cells during the weeks immediately after transfer, reactive cells are ultimately derived from the host itself (Elkins, 1973; Miyamoto and McCullagh, 1974). Not only are lymphoid cells from tolerant rats which have been injected recently with normal lymphocytes poorly responsive in a GvH assay, but they have been observed in some experiments to suppress the GvH activity of normal syngeneic lymphoid cells (Elkins, 1972; Atkins and Ford, 1972). It is not clear whether the cells mediating suppression of the normal lymphocytes were derived from the tolerant host itself or, alternatively, from the normal lymphocytes injected into it to terminate the tolerant state. The present experiments sought to delineate the origin of any suppressor cells within populations of lymphocytes collected from rats in which tolerance had recently been terminated. The indicate that suppression of the normal donor cells within such populations may be exerted by cells derived from the tolerant host.", "contents": "Suppressor cells in homograft tolerant rats. If sufficient normal syngeneic lymphocytes to effect skin graft rejection are transferred to homograft tolerant rats, a prolonged period elapses before lymphoid cells from the recipient acquire normal levels of GvH responsiveness against tissues of which the donor was previously tolerant (Silvers and Billingham, 1970; Elkins, 1972; Miyamoto and McCullagh, 1974). Although the ability of lymphoid populations of such animals to mount GvH reactions can be demonstrated to reside in donor type cells during the weeks immediately after transfer, reactive cells are ultimately derived from the host itself (Elkins, 1973; Miyamoto and McCullagh, 1974). Not only are lymphoid cells from tolerant rats which have been injected recently with normal lymphocytes poorly responsive in a GvH assay, but they have been observed in some experiments to suppress the GvH activity of normal syngeneic lymphoid cells (Elkins, 1972; Atkins and Ford, 1972). It is not clear whether the cells mediating suppression of the normal lymphocytes were derived from the tolerant host itself or, alternatively, from the normal lymphocytes injected into it to terminate the tolerant state. The present experiments sought to delineate the origin of any suppressor cells within populations of lymphocytes collected from rats in which tolerance had recently been terminated. The indicate that suppression of the normal donor cells within such populations may be exerted by cells derived from the tolerant host."}
{"id": "PMID:7223", "title": "Efficacy of two minor tranquilizers in relieveing symptoms of functional gastrointestinal distress.", "content": "Two minor  tranquilizers, diazepam and lorazepam were significantly better than a placebo preparation in relieving symptoms of functional gastrointestinal distress in 28 patients who took part in a double-blind cross-over trial. The beneficial therapeutic effect may be group- rather than preparation-specific. Both agents were also of significant benefit to the sub-group of patients with aerophagy as a major symptom.", "contents": "Efficacy of two minor tranquilizers in relieveing symptoms of functional gastrointestinal distress. Two minor  tranquilizers, diazepam and lorazepam were significantly better than a placebo preparation in relieving symptoms of functional gastrointestinal distress in 28 patients who took part in a double-blind cross-over trial. The beneficial therapeutic effect may be group- rather than preparation-specific. Both agents were also of significant benefit to the sub-group of patients with aerophagy as a major symptom."}
{"id": "PMID:7224", "title": "Hydrallazine and beta-blockade in refractory hypertension with characterization of acetylator phenotype.", "content": "In 30 refractory hypertensives a hydrallazine beta blocker combination was added to or substituted for previous antihypertensives. Over a mean period of 12 months a good or satisfactory blood pressure response resulted in 12 patients each, while six others had an unsatisfactory outcome. (Good = diastolic pressure (DP) less than 95 mmHg; Satisfactory = deltaDP greater than 15 mmHg or DP 95-105 mmHg; Unsatisfactory = DP greater than 105 mmHg or deltaDP less than 15mmHg.) Twelve of the patients had significant renal disease with serum creatinine greater than 2 mg/100 ml, but in these there was no evidence that renal hydrallazine retention potentiated an antihypertensive effect. Those with an unsatisfactory response were receiving slightly higher doses hydrallazine and propranol when compared with good responders. The average dose of hydrallazine was 258 mg/day and of propranolol 308 mg/day. Transient headache was not uncommon at the commencement of hydrallazine therapy. Angina and vertebro-basilar insufficiency were each aggravated in one patient, but resolved with dosage adjustment. A lupuslike rash developed in one patient, a slow acetylator on 300 mg hydrallazine/day who had received a total of 92 g over eleven months. The genetically determined acetylator phenotype was assessed in 75 subjects. A little over one third were found to be rapid acetylators. Those with slow acetylator phenotype did not show a more favourable phenotype did not show a more favourable blood-pressure response to equivalent doses of hydrallazine.", "contents": "Hydrallazine and beta-blockade in refractory hypertension with characterization of acetylator phenotype. In 30 refractory hypertensives a hydrallazine beta blocker combination was added to or substituted for previous antihypertensives. Over a mean period of 12 months a good or satisfactory blood pressure response resulted in 12 patients each, while six others had an unsatisfactory outcome. (Good = diastolic pressure (DP) less than 95 mmHg; Satisfactory = deltaDP greater than 15 mmHg or DP 95-105 mmHg; Unsatisfactory = DP greater than 105 mmHg or deltaDP less than 15mmHg.) Twelve of the patients had significant renal disease with serum creatinine greater than 2 mg/100 ml, but in these there was no evidence that renal hydrallazine retention potentiated an antihypertensive effect. Those with an unsatisfactory response were receiving slightly higher doses hydrallazine and propranol when compared with good responders. The average dose of hydrallazine was 258 mg/day and of propranolol 308 mg/day. Transient headache was not uncommon at the commencement of hydrallazine therapy. Angina and vertebro-basilar insufficiency were each aggravated in one patient, but resolved with dosage adjustment. A lupuslike rash developed in one patient, a slow acetylator on 300 mg hydrallazine/day who had received a total of 92 g over eleven months. The genetically determined acetylator phenotype was assessed in 75 subjects. A little over one third were found to be rapid acetylators. Those with slow acetylator phenotype did not show a more favourable phenotype did not show a more favourable blood-pressure response to equivalent doses of hydrallazine."}
{"id": "PMID:7225", "title": "Neurotic and psychotic states attributed to Thai \"Phii Pob\" spirit possession.", "content": "In Thailand, the term \"Phii\" refers to spirits and ghosts to which are generally attributed power over human beings. In the present, spirit possession is usually found in rural areas. However among several spirits, there is one particularly interesting spirit selected for this presentation, the phii pob. The \"Phii Pob\" is a common spirit in the Northeast, North and some provinces in the Central part of Thailand (Suwanlert, 1972). Thai believers consider that the phii pob differs from other spirits. It originates in a living person, then conceals itself in the body of that person, who is called th originating host; it is believed that the phii pob hiding within a person can leave the body of that person to possess another, who is called the possessed host. The victims almost always are females.", "contents": "Neurotic and psychotic states attributed to Thai \"Phii Pob\" spirit possession. In Thailand, the term \"Phii\" refers to spirits and ghosts to which are generally attributed power over human beings. In the present, spirit possession is usually found in rural areas. However among several spirits, there is one particularly interesting spirit selected for this presentation, the phii pob. The \"Phii Pob\" is a common spirit in the Northeast, North and some provinces in the Central part of Thailand (Suwanlert, 1972). Thai believers consider that the phii pob differs from other spirits. It originates in a living person, then conceals itself in the body of that person, who is called th originating host; it is believed that the phii pob hiding within a person can leave the body of that person to possess another, who is called the possessed host. The victims almost always are females."}
{"id": "PMID:7231", "title": "The effects of acidosis and alkalosis on coronary flow and cardiac nucleotide metabolism.", "content": "The changes of the coronary flows and of the cardiac nucleotide metabolism during acidosis and during alkalosis were studied in 50 perfused guinea pig hearts with and without hypoxia. At pH 7.0 the coronary flows increased, and at pH 7.8 a significant reduction of the flows took place. At 20% O2, acidosis elicited a further flow increase, whereas alkalosis inhibited the flow increase produced by hyoxia. The increases after adenosine injections and after coronary occlusions were greater during acidosis and smaller during alkalosis than at pH 7.4. The cardiac nucleotide contents did not clearly differ from the controls whereas adenosine exhibits higher levels in acidotic hearts. Alkalosis always induced a decreased production of adenine nucleoside irrespective of the presence or the absence of hypoxia. At 20% O2 a decreased ATP level and increased ADP- and CrP-contents could be observed during alkalosis.", "contents": "The effects of acidosis and alkalosis on coronary flow and cardiac nucleotide metabolism. The changes of the coronary flows and of the cardiac nucleotide metabolism during acidosis and during alkalosis were studied in 50 perfused guinea pig hearts with and without hypoxia. At pH 7.0 the coronary flows increased, and at pH 7.8 a significant reduction of the flows took place. At 20% O2, acidosis elicited a further flow increase, whereas alkalosis inhibited the flow increase produced by hyoxia. The increases after adenosine injections and after coronary occlusions were greater during acidosis and smaller during alkalosis than at pH 7.4. The cardiac nucleotide contents did not clearly differ from the controls whereas adenosine exhibits higher levels in acidotic hearts. Alkalosis always induced a decreased production of adenine nucleoside irrespective of the presence or the absence of hypoxia. At 20% O2 a decreased ATP level and increased ADP- and CrP-contents could be observed during alkalosis."}
{"id": "PMID:7235", "title": "Biosynthesis of prostaglandins in rabbit kidney medulla. Properties of prostaglandin synthase.", "content": "A simple radioactive-substrate assay for prostaglandin synthase (EC 1.14.99.1), which uses t.l.c. to measure simultaneously different prostaglandins synthesized from one precursor substrate, was developed. Rabbit kidney-medulla prostaglandin synthase catalyses the formation of prostaglandin E2, prostaglandin F2alpha and prostaglandin D2 from arachidonic acid. Fractionation of crude homogenates indicated that the microsomal fraction possessed the highest specific activity of prostaglandin synthase, whereas the soluble fraction exhibited little enzyme activity but rather contained a heat-labile inhibitory macromolecular factor(s), which might be attributed to the serum albumin present in this fraction. The microsomal fraction possessed low intrinsic enzyme activity, but the actvity could be fully stimulated by the presence of both GSH (reduced glutathione) and a phenolic cofactor. Only cysteine could partially replace GSH, whereas other thiols were inactive and some were even inhibitory. A variety of phenolic compounds, including catecholamines, dopamine (3,4-dihydroxyphenethylamine), 5-hydroxytryptamine and quinol, were active in stimulating prostaglandin synthase. In all cases, the stimulation was reflected in the synthesis of all three prostaglandins with ratios not significantly altered by different phenolic cofactors. The synthesis of each of the different prostaglandins appeared to have similar pH optima. The enzyme system was not inhibited by thiol-group inhibitors or a variety of metal chelators except for cyanide and 8-hydroxyquinoline. Characterization of the kidney-medulla prostaglandin synthase system indicated that it exhibited properties similar to those of the enzyme system present in seminal vesicles.", "contents": "Biosynthesis of prostaglandins in rabbit kidney medulla. Properties of prostaglandin synthase. A simple radioactive-substrate assay for prostaglandin synthase (EC 1.14.99.1), which uses t.l.c. to measure simultaneously different prostaglandins synthesized from one precursor substrate, was developed. Rabbit kidney-medulla prostaglandin synthase catalyses the formation of prostaglandin E2, prostaglandin F2alpha and prostaglandin D2 from arachidonic acid. Fractionation of crude homogenates indicated that the microsomal fraction possessed the highest specific activity of prostaglandin synthase, whereas the soluble fraction exhibited little enzyme activity but rather contained a heat-labile inhibitory macromolecular factor(s), which might be attributed to the serum albumin present in this fraction. The microsomal fraction possessed low intrinsic enzyme activity, but the actvity could be fully stimulated by the presence of both GSH (reduced glutathione) and a phenolic cofactor. Only cysteine could partially replace GSH, whereas other thiols were inactive and some were even inhibitory. A variety of phenolic compounds, including catecholamines, dopamine (3,4-dihydroxyphenethylamine), 5-hydroxytryptamine and quinol, were active in stimulating prostaglandin synthase. In all cases, the stimulation was reflected in the synthesis of all three prostaglandins with ratios not significantly altered by different phenolic cofactors. The synthesis of each of the different prostaglandins appeared to have similar pH optima. The enzyme system was not inhibited by thiol-group inhibitors or a variety of metal chelators except for cyanide and 8-hydroxyquinoline. Characterization of the kidney-medulla prostaglandin synthase system indicated that it exhibited properties similar to those of the enzyme system present in seminal vesicles."}
{"id": "PMID:7236", "title": "Interactions of some acceptors with superoxide anion radicals formed by the NADPH-specific flavoprotein in rat liver microsomal fractions.", "content": "In rat liver microsomal fractions oxidation of adrenaline was effected by superoxide anion radicals (O2-), whereas cytochrome c, 2,6-dichlorophenol-indophenol and ferricyanide accepted electrons from NADPH-specific flavoprotein only directly. Nitro Blue Tetrazolium was reduced both by O2- and by the direct acceptance of electrons. Elevation of pH and addition of menadione shift the Nitro Blue Tetrazolium reduction towards the O2--dependent pathway. From the values of the kinetic constants for interaction of adrenaline and Nitro Blue Tetrazolium with NADPH-specific flavoprotein, the rates of generation of O2- in rat liver microsomal fraction were determined.", "contents": "Interactions of some acceptors with superoxide anion radicals formed by the NADPH-specific flavoprotein in rat liver microsomal fractions. In rat liver microsomal fractions oxidation of adrenaline was effected by superoxide anion radicals (O2-), whereas cytochrome c, 2,6-dichlorophenol-indophenol and ferricyanide accepted electrons from NADPH-specific flavoprotein only directly. Nitro Blue Tetrazolium was reduced both by O2- and by the direct acceptance of electrons. Elevation of pH and addition of menadione shift the Nitro Blue Tetrazolium reduction towards the O2--dependent pathway. From the values of the kinetic constants for interaction of adrenaline and Nitro Blue Tetrazolium with NADPH-specific flavoprotein, the rates of generation of O2- in rat liver microsomal fraction were determined."}
{"id": "PMID:7237", "title": "L-lactate transport in Ehrlich ascites-tumour cells.", "content": "Ehrlich ascites-tumour cells were investigated with regard to their stability to transport L-lactate by measuring either the distribution of [14C]lactate or concomitant H+ ion movements. The movement of lactate was dependent on the pH difference across the cell membrane and was electroneutral, as evidenced by an observed 1:1 antiport for OH- ions or 1:1 symport with H+ ions. 2. Kinetic experiments showed that lactate transport was saturable, with an apparent Km of approx. 4.68 mM and a Vmax. as high as 680 nmol/min per mg of protein at pH 6.2 and 37 degrees C. 3. Lactate transport exhibited a high temperature dependence (activation energy = 139 kJ/mol). 4. Lactate transport was inhibited competitively by (a) a variety of other substituted monocarboxylic acids (e.g. pyruvate, Ki = 6.3 mM), which were themselves transported, (b) the non-transportable analogues alpha-cyano-4-hydroxycinnamate (Ki = 0.5 mM), alpha-cyano-3-hydroxycinnamate (Ki = 2mM) and DL-p-hydroxyphenyl-lactate (Ki = 3.6 mM) and (c) the thiol-group reagent mersalyl (Ki = 125 muM). 5. Transport of simple monocarboxylic acids, including acetate and propionate, was insensitive to these inhibitors; they presumably cross the membrane by means of a different mechanism. 6. Experiments using saturating amounts of mersalyl as an \"inhibitor stop\" allowed measurements of the initial rates of net influx and of net efflux of [14C]lactate. Influx and efflux of lactate were judged to be symmetrical reactions in that they exhibited similar concentration dependence. 7. It is concluded that lactate transport in Ehrlich ascites-tumour cells is mediated by a carrier capable of transporting a number of other substituted monocarboxylic acids, but not unsubstituted short-chain aliphatic acids.", "contents": "L-lactate transport in Ehrlich ascites-tumour cells. Ehrlich ascites-tumour cells were investigated with regard to their stability to transport L-lactate by measuring either the distribution of [14C]lactate or concomitant H+ ion movements. The movement of lactate was dependent on the pH difference across the cell membrane and was electroneutral, as evidenced by an observed 1:1 antiport for OH- ions or 1:1 symport with H+ ions. 2. Kinetic experiments showed that lactate transport was saturable, with an apparent Km of approx. 4.68 mM and a Vmax. as high as 680 nmol/min per mg of protein at pH 6.2 and 37 degrees C. 3. Lactate transport exhibited a high temperature dependence (activation energy = 139 kJ/mol). 4. Lactate transport was inhibited competitively by (a) a variety of other substituted monocarboxylic acids (e.g. pyruvate, Ki = 6.3 mM), which were themselves transported, (b) the non-transportable analogues alpha-cyano-4-hydroxycinnamate (Ki = 0.5 mM), alpha-cyano-3-hydroxycinnamate (Ki = 2mM) and DL-p-hydroxyphenyl-lactate (Ki = 3.6 mM) and (c) the thiol-group reagent mersalyl (Ki = 125 muM). 5. Transport of simple monocarboxylic acids, including acetate and propionate, was insensitive to these inhibitors; they presumably cross the membrane by means of a different mechanism. 6. Experiments using saturating amounts of mersalyl as an \"inhibitor stop\" allowed measurements of the initial rates of net influx and of net efflux of [14C]lactate. Influx and efflux of lactate were judged to be symmetrical reactions in that they exhibited similar concentration dependence. 7. It is concluded that lactate transport in Ehrlich ascites-tumour cells is mediated by a carrier capable of transporting a number of other substituted monocarboxylic acids, but not unsubstituted short-chain aliphatic acids."}
{"id": "PMID:7238", "title": "Dehydrogenation of the phosphonate analogue of glucose 6-phosphate by glucose 6-phosphate dehydrogenase.", "content": "6,7 -Dideoxy-alpha-D-gluco-heptose 7-phosphonic acid, the isosteric phosphonate analogue of glucose 6-phosphate, was synthesized in six steps from the readily available precursor benzyl 4,6-O-benzylidene-alpha-D-glucopyranoside. The analogue is a substrate for yeast glucose 6-phosphate dehydrogenase, showing Michaelis-Menten kinetics at pH7.5 and 8.0. At both pH values the Km values of the analogue are 4-5 fold higher and the values approx. 50% lower than those of the natural substrate. The product of enzymic dehydrogenation of the phosphonate analogue at pH8.5 is itself a substrate for gluconate 6-phosphate dehydrogenase.", "contents": "Dehydrogenation of the phosphonate analogue of glucose 6-phosphate by glucose 6-phosphate dehydrogenase. 6,7 -Dideoxy-alpha-D-gluco-heptose 7-phosphonic acid, the isosteric phosphonate analogue of glucose 6-phosphate, was synthesized in six steps from the readily available precursor benzyl 4,6-O-benzylidene-alpha-D-glucopyranoside. The analogue is a substrate for yeast glucose 6-phosphate dehydrogenase, showing Michaelis-Menten kinetics at pH7.5 and 8.0. At both pH values the Km values of the analogue are 4-5 fold higher and the values approx. 50% lower than those of the natural substrate. The product of enzymic dehydrogenation of the phosphonate analogue at pH8.5 is itself a substrate for gluconate 6-phosphate dehydrogenase."}
{"id": "PMID:7239", "title": "Interactions of the lanthanide- and hapten-binding sites in the Fv fragment from the myeloma protein MOPC 315.", "content": "1. The interactions of lanthanide metals and dinitrophenyl spin-label haptens with the Fv fragment of the mouse myeloma protein MOPC 315 were investigated by the techniques of fluorescence, e.s.r. (electron spin resonance) and high-resolution n.m.r. (nuclear magnetic resonance). 2. The protein fluorescence of Fv fragment at 340nm is quenched by the haptens (fluorescence enhancement, epsilon=0.15) and enhanced by Gd(III) (epsilon=1.14) and other lanthanides. The binding of the haptens studied here is insensitive to pH in the range 5.5-7.0 (dissociation constant KH=0.3-1.0 muM) and shows 1:1 stoicheiometry. The binding of Gd(III) also shows 1:1 stoicheiometry, but is pH-dependent; the binding constant (KM) varies from 10 muM at pH7.0 to 700 muM at pH4.8. La(III) binding is less sensitive to pH. The pH-dependences of the metal-binding constants imply that a group in the protein with pKa greater than or equal to 6.2 is involved in the binding, and probably also other groups with lower pKa values. 3. The apparent binding of the haptens is weakened about 20-fold by Gd(III), and vice versa. An equilibrium scheme involving a ternary complex with an interaction between the two binding sites is derived in Appendix I to explain the experimental results at two pH values. 4. Time-dependent fluorescence changes are observed in the presence of Gd(III) at pH5.5. A two-state kinetic scheme involving a 'slow' conformational change in the Fv fragment is derived in Appendix II to explain this time-dependence. This scheme is consistent with the antagonistic equilibrium behaviour. 5. The e.s.r. changes in the spin-label haptens on binding to Fv fragment and on the subsequent addition of lanthanides are consistent with the binding scheme for haptens and lanthanides proposed from the fluorescence studies. A difference between the limiting quenching of the e.s.r. signal from the bound haptens in the presence of saturating concentrations of Gd(III) and La(III) is attributed to dipolar interactions between bound Gd(III) and the nitroxide moiety of the bound hapten. The residual quenching with Gd(III) allows an estimate of 1.2nm to be made for the distance between the two paramagnetic centres. 6. The 270 MHz proton difference spectrum of the Fv fragment resulting from the addition of La(III) suggests that any metal-induced conformational changes are small and involve relatively few amino acid residues on the Fv fragment...", "contents": "Interactions of the lanthanide- and hapten-binding sites in the Fv fragment from the myeloma protein MOPC 315. 1. The interactions of lanthanide metals and dinitrophenyl spin-label haptens with the Fv fragment of the mouse myeloma protein MOPC 315 were investigated by the techniques of fluorescence, e.s.r. (electron spin resonance) and high-resolution n.m.r. (nuclear magnetic resonance). 2. The protein fluorescence of Fv fragment at 340nm is quenched by the haptens (fluorescence enhancement, epsilon=0.15) and enhanced by Gd(III) (epsilon=1.14) and other lanthanides. The binding of the haptens studied here is insensitive to pH in the range 5.5-7.0 (dissociation constant KH=0.3-1.0 muM) and shows 1:1 stoicheiometry. The binding of Gd(III) also shows 1:1 stoicheiometry, but is pH-dependent; the binding constant (KM) varies from 10 muM at pH7.0 to 700 muM at pH4.8. La(III) binding is less sensitive to pH. The pH-dependences of the metal-binding constants imply that a group in the protein with pKa greater than or equal to 6.2 is involved in the binding, and probably also other groups with lower pKa values. 3. The apparent binding of the haptens is weakened about 20-fold by Gd(III), and vice versa. An equilibrium scheme involving a ternary complex with an interaction between the two binding sites is derived in Appendix I to explain the experimental results at two pH values. 4. Time-dependent fluorescence changes are observed in the presence of Gd(III) at pH5.5. A two-state kinetic scheme involving a 'slow' conformational change in the Fv fragment is derived in Appendix II to explain this time-dependence. This scheme is consistent with the antagonistic equilibrium behaviour. 5. The e.s.r. changes in the spin-label haptens on binding to Fv fragment and on the subsequent addition of lanthanides are consistent with the binding scheme for haptens and lanthanides proposed from the fluorescence studies. A difference between the limiting quenching of the e.s.r. signal from the bound haptens in the presence of saturating concentrations of Gd(III) and La(III) is attributed to dipolar interactions between bound Gd(III) and the nitroxide moiety of the bound hapten. The residual quenching with Gd(III) allows an estimate of 1.2nm to be made for the distance between the two paramagnetic centres. 6. The 270 MHz proton difference spectrum of the Fv fragment resulting from the addition of La(III) suggests that any metal-induced conformational changes are small and involve relatively few amino acid residues on the Fv fragment..."}
{"id": "PMID:7240", "title": "Isolation, by partial pepsin digestion, of the three collagen-like regions present in subcomponent Clq of the first component of human complement.", "content": "1. Digestion of human subcomponent C1q with pepsin at pH4.45 for 20h at 37 degrees C fragmented most of the non-collagen-like amino acid sequences in the molecule to small peptides, whereas the entire regions of collagen-like sequence that comprised 38% by weight of the subcomponent C1q were left intact. 2. The collagen-like fraction of the digest was eluted in the void volume of a Sephadex G-200 column, was was showm to be composed of two major fragments when examined by electrophoresis on polyacrylamide gels run in buffers containing sodium dodecyl sulphate. These fragments were separated on CM-cellulose at pH4.9 in buffers containing 7.5M-urea. 3. Human subcomponent C1q on reduction and alkylation yields equimolar amounnts of three chains, which have been designated A, B and C [Reid et al. (1972) Biochem. J. 130, 749-763]. One of the pepsin fragments was shown to be composed of the N-terminal 95 residues of the A chain linked, via residue A4, by a single disulphide bond to a residue in the sequence B2-B6 in the N-terminal 91 residues of the B chain. The second pepsin fragment was shown to be composed of a disulphide-linked dimer of the N-terminal 94 residues of the C chain, the only disulphide bond being located at residue C4.4. The mol. wts. of the unoxidized and oxidized pepsin fragments were estimated from their amino acid compositions to be 20 000 and 18 200 for the A-B and C-C dimers and 11 400, 8800 and 9600 for the collagen-like fragments of the A, B and C chains respectively. Estimation of the molecular weights of the peptic fragments by polyacrylamide-gel electrophoresis run in the presence of sodium dodecyl sulphate gave values that were approx. 50% higher than expected from the amino acid sequence data. This is probably due to the high collagen-like sequence content of these fragments.", "contents": "Isolation, by partial pepsin digestion, of the three collagen-like regions present in subcomponent Clq of the first component of human complement. 1. Digestion of human subcomponent C1q with pepsin at pH4.45 for 20h at 37 degrees C fragmented most of the non-collagen-like amino acid sequences in the molecule to small peptides, whereas the entire regions of collagen-like sequence that comprised 38% by weight of the subcomponent C1q were left intact. 2. The collagen-like fraction of the digest was eluted in the void volume of a Sephadex G-200 column, was was showm to be composed of two major fragments when examined by electrophoresis on polyacrylamide gels run in buffers containing sodium dodecyl sulphate. These fragments were separated on CM-cellulose at pH4.9 in buffers containing 7.5M-urea. 3. Human subcomponent C1q on reduction and alkylation yields equimolar amounnts of three chains, which have been designated A, B and C [Reid et al. (1972) Biochem. J. 130, 749-763]. One of the pepsin fragments was shown to be composed of the N-terminal 95 residues of the A chain linked, via residue A4, by a single disulphide bond to a residue in the sequence B2-B6 in the N-terminal 91 residues of the B chain. The second pepsin fragment was shown to be composed of a disulphide-linked dimer of the N-terminal 94 residues of the C chain, the only disulphide bond being located at residue C4.4. The mol. wts. of the unoxidized and oxidized pepsin fragments were estimated from their amino acid compositions to be 20 000 and 18 200 for the A-B and C-C dimers and 11 400, 8800 and 9600 for the collagen-like fragments of the A, B and C chains respectively. Estimation of the molecular weights of the peptic fragments by polyacrylamide-gel electrophoresis run in the presence of sodium dodecyl sulphate gave values that were approx. 50% higher than expected from the amino acid sequence data. This is probably due to the high collagen-like sequence content of these fragments."}
{"id": "PMID:7241", "title": "PH-dependence of the steady-state rate of a two-step enzymic reaction.", "content": "1. The pH-dependence is considered of a reaction between E and S that proceeds through an intermediate ES under \"Briggs-Haldane' conditions, i.e. there is a steady state in ES and [S]o greater than [E]T, where [S]o is the initial concentration of S and [E]T is the total concentration of all forms of E. Reactants and intermediates are assumed to interconvert in three protonic states (E equilibrium ES; EH equilibrium EHS; EH2 equilibrium EH2S), but only EHS provides products by an irreversible reaction whose rate constant is kcat. Protonations are assumed to be so fast that they are all at equilibrium. 2. The rate equation for this model is shown to be v = d[P]/dt = (kcat.[E]T[S]o/A)/[(KmBC/DA) +  [S]o], where Km is the usual assembly of rate constants around EHS and A-D are functions of the form (1 + [H]/K1 + K2/[H]), in which K1 and K2 are: in A, the molecular ionization constants of ES; in B, the analogous constants of E; in C and D, apparent ionization constants composed of molecular ionization constants (of E or ES) and assemblies of rate constants. 3. As in earlier treatments of this type of reaction which involve either the assumption that the reactants and intermediate are in equilibrium or the assumption of Peller & Alberty [(1959) J. Am. Chem. Soc. 81, 5907-5914] that only EH and EHS interconvert directly, the pH-dependence of kcat. is determined only by A. 4. The pH-dependence of Km is determined in general by B-C/A-D, but when reactants and intermediate are in equilibrium, C identical to D and this expression simplifies to B/A. 5. The pH-dependence of kcat./Km, i.e. of the rate when [S]o less than Km, is not necessarily a simple bell-shaped curve characterized only by the ionization constants of B, but is a complex curve characterized by D/B-C. 6. Various situations are discussed in which the pH-dependence of kcat./Km is determined by assemblies simpler than D/B-C. The special situation in which a kcat./Km-pH profile provides the molecular pKa values of the intermediate ES complex is delineated.", "contents": "PH-dependence of the steady-state rate of a two-step enzymic reaction. 1. The pH-dependence is considered of a reaction between E and S that proceeds through an intermediate ES under \"Briggs-Haldane' conditions, i.e. there is a steady state in ES and [S]o greater than [E]T, where [S]o is the initial concentration of S and [E]T is the total concentration of all forms of E. Reactants and intermediates are assumed to interconvert in three protonic states (E equilibrium ES; EH equilibrium EHS; EH2 equilibrium EH2S), but only EHS provides products by an irreversible reaction whose rate constant is kcat. Protonations are assumed to be so fast that they are all at equilibrium. 2. The rate equation for this model is shown to be v = d[P]/dt = (kcat.[E]T[S]o/A)/[(KmBC/DA) +  [S]o], where Km is the usual assembly of rate constants around EHS and A-D are functions of the form (1 + [H]/K1 + K2/[H]), in which K1 and K2 are: in A, the molecular ionization constants of ES; in B, the analogous constants of E; in C and D, apparent ionization constants composed of molecular ionization constants (of E or ES) and assemblies of rate constants. 3. As in earlier treatments of this type of reaction which involve either the assumption that the reactants and intermediate are in equilibrium or the assumption of Peller & Alberty [(1959) J. Am. Chem. Soc. 81, 5907-5914] that only EH and EHS interconvert directly, the pH-dependence of kcat. is determined only by A. 4. The pH-dependence of Km is determined in general by B-C/A-D, but when reactants and intermediate are in equilibrium, C identical to D and this expression simplifies to B/A. 5. The pH-dependence of kcat./Km, i.e. of the rate when [S]o less than Km, is not necessarily a simple bell-shaped curve characterized only by the ionization constants of B, but is a complex curve characterized by D/B-C. 6. Various situations are discussed in which the pH-dependence of kcat./Km is determined by assemblies simpler than D/B-C. The special situation in which a kcat./Km-pH profile provides the molecular pKa values of the intermediate ES complex is delineated."}
{"id": "PMID:7242", "title": "Some properties of a microsomal oleate desaturase from leaves.", "content": "1. When [1-14C]oleoyl-CoA was incubated with a pea-leaf homogenate oleate was both incorporated into microsomal 3-sn-phosphatidylcholine and released as the unesterified fatty acid. The proportion of oleate incorporated into this phospholipid was dependent on the relative amounts of thiol ester and microsomal preparation present in reactions. 2. At the concentrations of microsomal preparation and [14C]oleoyl-CoA used to study oleate desaturation the metabolism of the thiol ester was essentially complete after 5 min incubation, but the loss of label from 3-sn-phosphatidylcholine oleate and the concomitant increase in radioactivity in the linoleate of this phospholipid proceeded at approximately linear rates over a 60 min period. The kinetics of labelling of unesterified linoleate was consistent with the view that this labelled fatty acid was derived from 3-sn-phosphatidylcholine. 3. Oleate desaturation required oxygen and with unwashed microsomal fractions was stimulated either by NADPH or by the 105 000g supernatant. Washed microsomal preparations did not catalyse desaturation, but actively was restored by the addition of NADPH, 105 000G supernatant or Sephadex-treated supernatant. NADPH could be replaced by NADH or NADP+, but not by NAD+. 4. Microsomal fractions from mature and immature maize lamina and expanding spinach leaves also rapidly incorporated oleate from ([14C]oleoyl-CoA into 3-sn-phosphatidylcholine, but desaturation of 3-sn-phosphatidylcholine oleate was detected only with microsomal preparations from immature maize lamina. 5. It is proposed that leaf microsomal preparations posses an oleate desaturase for which 3-sn-phosphatidylcholine oleate is either the substrate or an immediate precursor of the substrate.", "contents": "Some properties of a microsomal oleate desaturase from leaves. 1. When [1-14C]oleoyl-CoA was incubated with a pea-leaf homogenate oleate was both incorporated into microsomal 3-sn-phosphatidylcholine and released as the unesterified fatty acid. The proportion of oleate incorporated into this phospholipid was dependent on the relative amounts of thiol ester and microsomal preparation present in reactions. 2. At the concentrations of microsomal preparation and [14C]oleoyl-CoA used to study oleate desaturation the metabolism of the thiol ester was essentially complete after 5 min incubation, but the loss of label from 3-sn-phosphatidylcholine oleate and the concomitant increase in radioactivity in the linoleate of this phospholipid proceeded at approximately linear rates over a 60 min period. The kinetics of labelling of unesterified linoleate was consistent with the view that this labelled fatty acid was derived from 3-sn-phosphatidylcholine. 3. Oleate desaturation required oxygen and with unwashed microsomal fractions was stimulated either by NADPH or by the 105 000g supernatant. Washed microsomal preparations did not catalyse desaturation, but actively was restored by the addition of NADPH, 105 000G supernatant or Sephadex-treated supernatant. NADPH could be replaced by NADH or NADP+, but not by NAD+. 4. Microsomal fractions from mature and immature maize lamina and expanding spinach leaves also rapidly incorporated oleate from ([14C]oleoyl-CoA into 3-sn-phosphatidylcholine, but desaturation of 3-sn-phosphatidylcholine oleate was detected only with microsomal preparations from immature maize lamina. 5. It is proposed that leaf microsomal preparations posses an oleate desaturase for which 3-sn-phosphatidylcholine oleate is either the substrate or an immediate precursor of the substrate."}
{"id": "PMID:7243", "title": "Isolation and properties of alpha-D-mannosidase from human kidney.", "content": "Alpha-D-Mannosidase activity exists in three forms that can be separated by DEAE-cellulose chromatography, alpha-D-Mannosidase was isolated from human kidney in a homogeneous state, and was purified 2100-fold, with p-nitrophenyl alpha-D-mannoside as substrate. The purified alpha-D-mannosidase was practically free from all other glycosidases tested. The Km of the synthetic substrate with the enzyme was 1 X 10(-3) M and the pH optimum 4.5. It was inhibited by heavy metals, sodium dodecyl sulphate, urea and compounds that react with the thiol groups, and was activated by Zn2+, Na+, 2-mercaptoethanol, human albumin and gamma-globulin. The mol. wt. of the enzyme was estimated to be 180 000 +/- 4500. After pretreatment with 2-mercaptoethanol and sodium dodecyl sulphate, alpha-D-mannosidase dissociated into subunits of mol. wts. of 58 000 +/- 600 and 30 000 +/- 380 respectively. Subunits of the same molecular weights were also obtained after the enzyme was heated at 100 degrees C.", "contents": "Isolation and properties of alpha-D-mannosidase from human kidney. Alpha-D-Mannosidase activity exists in three forms that can be separated by DEAE-cellulose chromatography, alpha-D-Mannosidase was isolated from human kidney in a homogeneous state, and was purified 2100-fold, with p-nitrophenyl alpha-D-mannoside as substrate. The purified alpha-D-mannosidase was practically free from all other glycosidases tested. The Km of the synthetic substrate with the enzyme was 1 X 10(-3) M and the pH optimum 4.5. It was inhibited by heavy metals, sodium dodecyl sulphate, urea and compounds that react with the thiol groups, and was activated by Zn2+, Na+, 2-mercaptoethanol, human albumin and gamma-globulin. The mol. wt. of the enzyme was estimated to be 180 000 +/- 4500. After pretreatment with 2-mercaptoethanol and sodium dodecyl sulphate, alpha-D-mannosidase dissociated into subunits of mol. wts. of 58 000 +/- 600 and 30 000 +/- 380 respectively. Subunits of the same molecular weights were also obtained after the enzyme was heated at 100 degrees C."}
{"id": "PMID:7244", "title": "Neutral proteinases of human spleen. Purification and criteria for homogeneity of elastase and cathepsin G.", "content": "1. Human spleen was found to contain proteinases active against azo-casein at neutral and alkaline pH values. 2. The activity was stimulated by high ionic strength and some detergents. 3. Optimal extraction of the proteinases from the tissue was achieved with 1.0M-NaCl containing 0.1% Brij 35 and 0.1% trisodium EDTA. 4. The proteinases were efficiently adsorbed to insoluble material in the absence of salt in the initial stages of purification. 5. Two distinct proteinases were separated by chromatography on DEAE-cellulose, an elastase and a chymotrypsin-like enzyme designated cathepsin G. 6. Both enzymes were highly purified by further column chromatography. 7. The molecular weights of the enzymes were estimated by gel chromatography and sodium dodecyl sulphate-gel electrophoresis. 8. It was shown by isoelectric focusing and gel electrophoresis that both enzymes are cationic proteins that occur in multiple forms.", "contents": "Neutral proteinases of human spleen. Purification and criteria for homogeneity of elastase and cathepsin G. 1. Human spleen was found to contain proteinases active against azo-casein at neutral and alkaline pH values. 2. The activity was stimulated by high ionic strength and some detergents. 3. Optimal extraction of the proteinases from the tissue was achieved with 1.0M-NaCl containing 0.1% Brij 35 and 0.1% trisodium EDTA. 4. The proteinases were efficiently adsorbed to insoluble material in the absence of salt in the initial stages of purification. 5. Two distinct proteinases were separated by chromatography on DEAE-cellulose, an elastase and a chymotrypsin-like enzyme designated cathepsin G. 6. Both enzymes were highly purified by further column chromatography. 7. The molecular weights of the enzymes were estimated by gel chromatography and sodium dodecyl sulphate-gel electrophoresis. 8. It was shown by isoelectric focusing and gel electrophoresis that both enzymes are cationic proteins that occur in multiple forms."}
{"id": "PMID:7245", "title": "Human cathepsin G. Catalytic and immunological properties.", "content": "1. The specificity of cathepsin G, a neutral proteinase from human spleen, was examined by use of low-molecular-weight substrates. The enzyme was found to hydrolyse several synthetic substrates also hydrolysed by chymotrypsin, but with different kinetic constants. 2. Maximal activity against benzoyl-DL-phenylalanine 2-naphthol ester and azo-casein was in the range pH 7.5-8.0. 3. The sensitivity of cathepsin G to the action of potential inhibitors was determined, and compared with those of bovine chymotrypsin and subtilisin. Cathepsin G showed the characteristics of a serine proteinase, but was less affected by the chloromethyl ketone of tosylphenylalanine than was chymotrypsin. 4. A rabbit anti-(human cathepsin G) serum was raised, and precipitin lines formed in agarose gel were stained for activity of the enzyme. 5. Cathepsin G was shown to be immunologically identical with the chymotrypsin-like enzyme of the azurophil granules of the neutrophil granulocytes.", "contents": "Human cathepsin G. Catalytic and immunological properties. 1. The specificity of cathepsin G, a neutral proteinase from human spleen, was examined by use of low-molecular-weight substrates. The enzyme was found to hydrolyse several synthetic substrates also hydrolysed by chymotrypsin, but with different kinetic constants. 2. Maximal activity against benzoyl-DL-phenylalanine 2-naphthol ester and azo-casein was in the range pH 7.5-8.0. 3. The sensitivity of cathepsin G to the action of potential inhibitors was determined, and compared with those of bovine chymotrypsin and subtilisin. Cathepsin G showed the characteristics of a serine proteinase, but was less affected by the chloromethyl ketone of tosylphenylalanine than was chymotrypsin. 4. A rabbit anti-(human cathepsin G) serum was raised, and precipitin lines formed in agarose gel were stained for activity of the enzyme. 5. Cathepsin G was shown to be immunologically identical with the chymotrypsin-like enzyme of the azurophil granules of the neutrophil granulocytes."}
{"id": "PMID:7246", "title": "Polar-group behaviour in mixed monolayers of phospholipids and fusogenic lipids.", "content": "1. The surface potentials of mixed monolayers of synthetic phospholipids with lipids that are fusogenic for hen erythrocytes were investigated. 2. At pH 5.6 and 10, but not at pH2, mixed monolayers of the fusogenic lipid, glycerol mono-oleate, with phosphatidylcholine exhibited negative deviations from the ideality rule in surface potential per molecule which were accompanied by negative deviations in mean molecular area. 3. Interactions of this type were not seen with chemically related but non-fusogenic lipids, nor were they found in mixed monolayers of any of the lipids with phosphatidylethanolamine. 4. Experiments with dihexadecyl phosphate and hexadecyltrimethyl-ammonium indicated that the complete head group of phosphatidylcholine is required for its observed behaviour with fusogenic lipids. 5. Bivalent cations (Ca2+, UO2(2+) or Zn2+) in the subphase at pH 5.6 significantly modified the behaviour of mixed monolayers of fusogenic lipids with phospholipids; there was a parallel perturbing effect of fusogenic lipids on interactions between monolayers of phospholipids and bivalent cations. 6. Possible molecular interactions of fusogenic lipids with membrane phospholipids, and the role of Ca2+, are discussed which may be relevant to cell fusion in erythrocytes induced by low-melting lipids in the presence of Ca2+.", "contents": "Polar-group behaviour in mixed monolayers of phospholipids and fusogenic lipids. 1. The surface potentials of mixed monolayers of synthetic phospholipids with lipids that are fusogenic for hen erythrocytes were investigated. 2. At pH 5.6 and 10, but not at pH2, mixed monolayers of the fusogenic lipid, glycerol mono-oleate, with phosphatidylcholine exhibited negative deviations from the ideality rule in surface potential per molecule which were accompanied by negative deviations in mean molecular area. 3. Interactions of this type were not seen with chemically related but non-fusogenic lipids, nor were they found in mixed monolayers of any of the lipids with phosphatidylethanolamine. 4. Experiments with dihexadecyl phosphate and hexadecyltrimethyl-ammonium indicated that the complete head group of phosphatidylcholine is required for its observed behaviour with fusogenic lipids. 5. Bivalent cations (Ca2+, UO2(2+) or Zn2+) in the subphase at pH 5.6 significantly modified the behaviour of mixed monolayers of fusogenic lipids with phospholipids; there was a parallel perturbing effect of fusogenic lipids on interactions between monolayers of phospholipids and bivalent cations. 6. Possible molecular interactions of fusogenic lipids with membrane phospholipids, and the role of Ca2+, are discussed which may be relevant to cell fusion in erythrocytes induced by low-melting lipids in the presence of Ca2+."}
{"id": "PMID:7247", "title": "Phosphonomethyl analogues of hexose phosphates.", "content": "The analogue of fructose 1,6-bisphosphate in which the phosphate group, -O-PO3H2, on C-6 is replaced by the phosphonomethyl group, -CH2-PO3H2, was made enzymically from the corresponding analogue of 3-phosphoglycerate. It was a substrate for aldolase, which was used to form it, but not for fructose 1,6-bisphosphatase. It was hydrolysed chemically to yield the corresponding analogue of fructose 6-phosphate [i.e. 6-deoxy-6-(phosphonomethyl)-D-fructose, or, more strictly, 6,7-dideoxy-7-phosphono-D-arabino-2-heptulose]. This proved to be a substrate for the sequential actions of glucose 6-phosphate isomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Thus seven out of the nine enzymes of the glycolytic and pentose phosphate pathways so far tested catalyse the reactions of the phosphonomethyl isosteres of their substrates.", "contents": "Phosphonomethyl analogues of hexose phosphates. The analogue of fructose 1,6-bisphosphate in which the phosphate group, -O-PO3H2, on C-6 is replaced by the phosphonomethyl group, -CH2-PO3H2, was made enzymically from the corresponding analogue of 3-phosphoglycerate. It was a substrate for aldolase, which was used to form it, but not for fructose 1,6-bisphosphatase. It was hydrolysed chemically to yield the corresponding analogue of fructose 6-phosphate [i.e. 6-deoxy-6-(phosphonomethyl)-D-fructose, or, more strictly, 6,7-dideoxy-7-phosphono-D-arabino-2-heptulose]. This proved to be a substrate for the sequential actions of glucose 6-phosphate isomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Thus seven out of the nine enzymes of the glycolytic and pentose phosphate pathways so far tested catalyse the reactions of the phosphonomethyl isosteres of their substrates."}
{"id": "PMID:7275", "title": "A metal complexing property of furosemide and bumetanide: determination of pK and stability constant.", "content": "Furosemide and bumetanide have been found to have different pK values and undergo complex formation with several metal ions in dioxane-water solution. pK values of these diuretics were determined. Evidence for complex formation was provided by a drop in pH during complex formation, production of a characteristic color and precipitation.", "contents": "A metal complexing property of furosemide and bumetanide: determination of pK and stability constant. Furosemide and bumetanide have been found to have different pK values and undergo complex formation with several metal ions in dioxane-water solution. pK values of these diuretics were determined. Evidence for complex formation was provided by a drop in pH during complex formation, production of a characteristic color and precipitation."}
{"id": "PMID:7276", "title": "[Drug-drug interactions (author's transl)].", "content": "This short outline of drug-drug interactions does not claim to cover the entire field. The task of this paper is to illustrate the most important principles of drug-drug interactions by paradigms taken from the experience of the practitioner. One consequence of drug-drug interactions is the change in pharmacolinetic parameters important for the therapeutical effect of drugs in the organism. Very often the elucidation of the mechanisms of drug-drug interactions in man is impossible; therefore, for clinical pharmacologists experiments on animals remain the tool in order to gain more knowledge in this field.", "contents": "[Drug-drug interactions (author's transl)]. This short outline of drug-drug interactions does not claim to cover the entire field. The task of this paper is to illustrate the most important principles of drug-drug interactions by paradigms taken from the experience of the practitioner. One consequence of drug-drug interactions is the change in pharmacolinetic parameters important for the therapeutical effect of drugs in the organism. Very often the elucidation of the mechanisms of drug-drug interactions in man is impossible; therefore, for clinical pharmacologists experiments on animals remain the tool in order to gain more knowledge in this field."}
{"id": "PMID:7277", "title": "[Galenical possibilities and problems in protraction of drug effects (author's transl)].", "content": "In recent years, dosage forms with sustained release have obtained a significant importance. The technological possibilities for manufacturing are described as coating, embedding and matrix procedures. The range of auxiliary substances, which are responsible for the retardation of drug activity, reaches from lipophilic compounds as lipoids, fatty alcohols and compounds which are forming hydrogels as cellulose derivatives and natural polysaccharides to synthetic polymers derived from acrylic acid. The formulation of the dosage forms requires particular care in respect to the amount of initial and maintenance doses. On account of technological processes, for example during manufacturing of tablets, under certain circumstances the liberation rate is altered. In vitro test methods allow comparisons only then when the results can be counter-checked by in vitro experiments. The release of drug follows different mechanisms, which are described, entirely or in part, to be reactions following the time law of zero or first order. In special cases, a linear correlation is observed as a function of square root of time. The calculation of given special equations for events within the dosage form is feasible from blood-level values.", "contents": "[Galenical possibilities and problems in protraction of drug effects (author's transl)]. In recent years, dosage forms with sustained release have obtained a significant importance. The technological possibilities for manufacturing are described as coating, embedding and matrix procedures. The range of auxiliary substances, which are responsible for the retardation of drug activity, reaches from lipophilic compounds as lipoids, fatty alcohols and compounds which are forming hydrogels as cellulose derivatives and natural polysaccharides to synthetic polymers derived from acrylic acid. The formulation of the dosage forms requires particular care in respect to the amount of initial and maintenance doses. On account of technological processes, for example during manufacturing of tablets, under certain circumstances the liberation rate is altered. In vitro test methods allow comparisons only then when the results can be counter-checked by in vitro experiments. The release of drug follows different mechanisms, which are described, entirely or in part, to be reactions following the time law of zero or first order. In special cases, a linear correlation is observed as a function of square root of time. The calculation of given special equations for events within the dosage form is feasible from blood-level values."}
{"id": "PMID:7278", "title": "[Metabolic degradation of cartilage by leucocyte enzymes under the influence of antirheumatic drugs (author's transl)].", "content": "Lately the importance and participation of leucocytes in rheumatoid arthritis have been discussed. In order to study catabolic reactions in connective tissue we investigated the autolytic liberation of mucopolysaccharides in cartilage alone and in the presence of leucocyte enzymes. Factors of optimal experimental conditions, such as pH and constituents of incubation medium, incubation time and the number of leucocytes, were determined. In further experiments we studied the influence of antirheumatic drugs, such as sodium salicylate, phenylbutazone, pentosanpoly-sulfate and gold thiopolypeptide, on cartilage degradation. In our experiments only phenylbutazone and pentosanpoly-sulfate exerted an inhibitory effect on leucocyte-stimulated degradation of cartilage. The relevance of this finding for the therapeutic use of these drugs is evaluated.", "contents": "[Metabolic degradation of cartilage by leucocyte enzymes under the influence of antirheumatic drugs (author's transl)]. Lately the importance and participation of leucocytes in rheumatoid arthritis have been discussed. In order to study catabolic reactions in connective tissue we investigated the autolytic liberation of mucopolysaccharides in cartilage alone and in the presence of leucocyte enzymes. Factors of optimal experimental conditions, such as pH and constituents of incubation medium, incubation time and the number of leucocytes, were determined. In further experiments we studied the influence of antirheumatic drugs, such as sodium salicylate, phenylbutazone, pentosanpoly-sulfate and gold thiopolypeptide, on cartilage degradation. In our experiments only phenylbutazone and pentosanpoly-sulfate exerted an inhibitory effect on leucocyte-stimulated degradation of cartilage. The relevance of this finding for the therapeutic use of these drugs is evaluated."}
{"id": "PMID:7279", "title": "[MASCA-model of biochemical-pharmacological drug research/Part VIII: Examples (author's transl)].", "content": "In this report two examples (inhibition of alcohol dehydrogenase by pyridine and benzamide derivates) are given for the interpretation of the MASCA-model.", "contents": "[MASCA-model of biochemical-pharmacological drug research/Part VIII: Examples (author's transl)]. In this report two examples (inhibition of alcohol dehydrogenase by pyridine and benzamide derivates) are given for the interpretation of the MASCA-model."}
{"id": "PMID:7280", "title": "[In vitro inhibition of oxidative N-demethylation with carbon disulfide].", "content": "Earlier findings have shown that in experimental animals (rat) and in man inhaled carbon disulphide (CS2) reversibly inhibits the non-specific oxidative drug metabolism caused by hepatic microsomal enzymes. Very little is known concerning the underlying mechanism. The present investigations were undertaken to throw light on this question. After addition of an NADPH-regenerating system to liver microsomes isolated from adult female Wistar rats, the oxidative N-demethylation of aminopyrine was measured under simultaneous exposure to CS2 by quantitatively determining the formaldehyde obtained; the resulting data were evaluated using enzyme-kinetic parameters according to Lineweaver-Burk: 1. Following acute exposure to low and medium-grade CS2 concentrations (20-400 ppm/8 h), the pattern of inhibition in rat liver microsomes is identical to that obtained in normal liver microsomes to which CS2 had been added. This finding seems to suggest that the inhibitory process under in vivo and in vitro conditions is based on one and the same molecular mechanism. 2. Upon addition of CS2 the in vitro pattern of inhibition corresponds to a strong mixed-type inhibition. 3. It is concluded from the enzyme-kinetic behaviour that CS2 attacks at two different sites of the enzyme molecule: Binding to the first site is followed by inhibition, as evidenced by the rise of Km; after saturation of this site, a second site is occupied resulting in a reactivation and, beyond this, an activation of enzyme output, as shown by the decrease of Km. CS2 exhibits a high affinity for the first site, and a low affinity for the second site. Binding at the first site is reversible. The possibility that the active centre in the enzyme molecule is the site where binding of the inhibitor occurs is ruled out. 4. A continuous decrease of Vmax at increasing inhibitor concentration is causally related with the formation of an enzyme/substrate inhibitor complex. 5. The CS2 added to the microsomes can be eliminated by helium gas; this is followed by the return of the original enzyme activity. It is concluded from this behaviour that under in vitro conditions CS2 itself (rather than its metabolites) acts as the inhibitor. 6. Oxygen treatment of the microsome-containing reaction mixture enhances the inhibition. In substrate-free control mixtures, addition of CS2 was followed by the dose-dependent formation of formaldehyde; a causal explanation is not readily available at this time.", "contents": "[In vitro inhibition of oxidative N-demethylation with carbon disulfide]. Earlier findings have shown that in experimental animals (rat) and in man inhaled carbon disulphide (CS2) reversibly inhibits the non-specific oxidative drug metabolism caused by hepatic microsomal enzymes. Very little is known concerning the underlying mechanism. The present investigations were undertaken to throw light on this question. After addition of an NADPH-regenerating system to liver microsomes isolated from adult female Wistar rats, the oxidative N-demethylation of aminopyrine was measured under simultaneous exposure to CS2 by quantitatively determining the formaldehyde obtained; the resulting data were evaluated using enzyme-kinetic parameters according to Lineweaver-Burk: 1. Following acute exposure to low and medium-grade CS2 concentrations (20-400 ppm/8 h), the pattern of inhibition in rat liver microsomes is identical to that obtained in normal liver microsomes to which CS2 had been added. This finding seems to suggest that the inhibitory process under in vivo and in vitro conditions is based on one and the same molecular mechanism. 2. Upon addition of CS2 the in vitro pattern of inhibition corresponds to a strong mixed-type inhibition. 3. It is concluded from the enzyme-kinetic behaviour that CS2 attacks at two different sites of the enzyme molecule: Binding to the first site is followed by inhibition, as evidenced by the rise of Km; after saturation of this site, a second site is occupied resulting in a reactivation and, beyond this, an activation of enzyme output, as shown by the decrease of Km. CS2 exhibits a high affinity for the first site, and a low affinity for the second site. Binding at the first site is reversible. The possibility that the active centre in the enzyme molecule is the site where binding of the inhibitor occurs is ruled out. 4. A continuous decrease of Vmax at increasing inhibitor concentration is causally related with the formation of an enzyme/substrate inhibitor complex. 5. The CS2 added to the microsomes can be eliminated by helium gas; this is followed by the return of the original enzyme activity. It is concluded from this behaviour that under in vitro conditions CS2 itself (rather than its metabolites) acts as the inhibitor. 6. Oxygen treatment of the microsome-containing reaction mixture enhances the inhibition. In substrate-free control mixtures, addition of CS2 was followed by the dose-dependent formation of formaldehyde; a causal explanation is not readily available at this time."}
{"id": "PMID:7281", "title": "[The influence of neuroleptic drugs on urinary excretion of non-protein nitrogen (author's transl)].", "content": "During treatment with thioxanthenes or phenothiazines of schizophrenic patients non-protein nitrogen in urine was measured. The values were calculated in relation to the excretion of creatinine. a) Flupentixol or fluphenazine applied in optimal dosage, increased the excretion of urea and the amino acids asp, glu + gln, and gly. b) Moreover, if the drug induced a parkinsonoid (thioridazine) the excretion of ser and thr was increased, too. The usual desalting procedure by ion-exchanging resins before chromatography increases the contents of several amino acids, e.g. asp, asn, ala, gly, cys, ser, thr, indicating a breakdown of some instable products.", "contents": "[The influence of neuroleptic drugs on urinary excretion of non-protein nitrogen (author's transl)]. During treatment with thioxanthenes or phenothiazines of schizophrenic patients non-protein nitrogen in urine was measured. The values were calculated in relation to the excretion of creatinine. a) Flupentixol or fluphenazine applied in optimal dosage, increased the excretion of urea and the amino acids asp, glu + gln, and gly. b) Moreover, if the drug induced a parkinsonoid (thioridazine) the excretion of ser and thr was increased, too. The usual desalting procedure by ion-exchanging resins before chromatography increases the contents of several amino acids, e.g. asp, asn, ala, gly, cys, ser, thr, indicating a breakdown of some instable products."}
{"id": "PMID:7286", "title": "Gastric secretion and fermentation in the suckling pig.", "content": "1. The contribution to acidification of the stomach contents of pigs by hydrochloric acid secretion or by lactic acid produced by fermentation was studied in fifteen suckling pigs from six litters born and reared either in a 'conventional' environment or in an isolated 'clean' environment. Sequential samples of stomach contents obtained during periods of up to 24 h were analysed for their chloride and lactic acid contents, pH and total titratable acidity. These values gave a measure of organic and inorganic acids respectively. 2. Six pigs from two litters born and reared in a 'clean' environment had acid secretion in the stomach at 2 d of age, and the concentrations of lactic acid in stomach contents remained low (0-40 mmol/l) throughout the suckling period. 3. Eight pigs from three litters born and reared in a 'conventional' environment, and a ninth pig born in this environment but moved to the 'clean' environment at 24 h of age, had lactic acid in concentrations of up to 250 mmol/l in stomach contents within the 1st week of life. The pattern of lactic acid production (and hence the acidity of stomach contents) was governed by frequency of suckling. 4. Both between- and within-litter variation in the age of onset of HC1 secretion was evident in the group reared in a 'conventional' environment, and when HC1 secretion did occur it was usually accompanied by a reduction in lactic acid production. 5. It is concluded: (1) that the environment at birth is important in determining the fermentative ability of the stomach flora; (2) that if lactic acid is produced in large amounts in the stomach, it may partly or completely inhibit acidification by HC1.", "contents": "Gastric secretion and fermentation in the suckling pig. 1. The contribution to acidification of the stomach contents of pigs by hydrochloric acid secretion or by lactic acid produced by fermentation was studied in fifteen suckling pigs from six litters born and reared either in a 'conventional' environment or in an isolated 'clean' environment. Sequential samples of stomach contents obtained during periods of up to 24 h were analysed for their chloride and lactic acid contents, pH and total titratable acidity. These values gave a measure of organic and inorganic acids respectively. 2. Six pigs from two litters born and reared in a 'clean' environment had acid secretion in the stomach at 2 d of age, and the concentrations of lactic acid in stomach contents remained low (0-40 mmol/l) throughout the suckling period. 3. Eight pigs from three litters born and reared in a 'conventional' environment, and a ninth pig born in this environment but moved to the 'clean' environment at 24 h of age, had lactic acid in concentrations of up to 250 mmol/l in stomach contents within the 1st week of life. The pattern of lactic acid production (and hence the acidity of stomach contents) was governed by frequency of suckling. 4. Both between- and within-litter variation in the age of onset of HC1 secretion was evident in the group reared in a 'conventional' environment, and when HC1 secretion did occur it was usually accompanied by a reduction in lactic acid production. 5. It is concluded: (1) that the environment at birth is important in determining the fermentative ability of the stomach flora; (2) that if lactic acid is produced in large amounts in the stomach, it may partly or completely inhibit acidification by HC1."}
{"id": "PMID:7287", "title": "Broad-line nuclear magnetic resonance studies of chloroperoxidase.", "content": "Chloroperoxidase, a heme glycoprotein isolated from the mold Caldariomyces fumago, was studied by NMR relaxation techniques. Interaction of the chloride ion substrate with the enzyme may be analyzed as consisting of at least three contributions: a weak interaction with the iron atom, nonspecific anion-protein interactions, and a specific interaction generated at low pH. The data indicate that a specific interaction, which develops in parallel with enzyme activity at low pH, does not occur at the iron atom first coordination sphere site. The results are summarized in terms of an enzymatic mechanism not involving chloride ion coordination to the iron atom.", "contents": "Broad-line nuclear magnetic resonance studies of chloroperoxidase. Chloroperoxidase, a heme glycoprotein isolated from the mold Caldariomyces fumago, was studied by NMR relaxation techniques. Interaction of the chloride ion substrate with the enzyme may be analyzed as consisting of at least three contributions: a weak interaction with the iron atom, nonspecific anion-protein interactions, and a specific interaction generated at low pH. The data indicate that a specific interaction, which develops in parallel with enzyme activity at low pH, does not occur at the iron atom first coordination sphere site. The results are summarized in terms of an enzymatic mechanism not involving chloride ion coordination to the iron atom."}
{"id": "PMID:7288", "title": "Reaction of cytidine with semicarbazide in the presence of bisulfite. A rapid modification specific for single-stranded polynucleotide.", "content": "Semicarbazide reacted rapidly with 5,6-dihydrocytidine-6-sulfonate, which was formed from cytidine by addition of bisulfite across the 5,6-double bond. The transaminated product, 5,6-dihydro-4-semicarbazido-2-ketotopyrimidine-6-sulfonate ribofuranoside, was identified by comparison with that formed by treatment of 4-semicarbazido-2-ketopyrimidine ribofuranoside with bisulfite. The progress of the transamination was monitored spectrophotometrically by use of a strong absorbance of the product in alkali. The reaction between cytidine and the semicarbazide-bisulfite mixture was optimal at pH 4.5. Complete transformation of cytidine into the product required only 5 min with the use of 3M semicarbazide-1M sodium bisulfite, pH 5.0, at the reaction temperature 37 degrees C. The product was stable in unbuffered solution but in phosphate buffers it underwent elimination of bisulfite to give 4-semicarbazido-2-ketopyrimidine ribofuranoside. The rate of the elimination at pH 7.0 and 37 degrees C increased proportionally with the increase of the phosphate concentration. Complete elimination was obtained by treatment with 1 M sodium phosphate for 2 h. When heat-denatured calf-thymus DNA was treated with 3 M semicarbazide-1 M bisulfite at 37 degrees C and pH 5.0 the transamination of reactive cytosine residues was completed by 10 min of incubation. At 20 degrees C, it required 85 min of incubation. Cytosine residues in native DNA did not react at all even by prolonged incubations. The modified DNA samples were further treated with a phosphate buffer at pH 7, producing 4-semicarbazido-2-ketopyrimidine residues in the DNA. Analysis of the base compositions of these samples by perchloric acid hydrolysis showed that the modification was selective to cytosine, which had been expected from studies with monomers. It also showed that the reactive cytosine residues in the denatured DNA, constitute about 80% of the total cytosine, which was consistent with the view that heat-denatured DNA still contains a considerable amount of secondary structure. The semicarbazide-bisulfite modification is expected to be a sensitive method to locate cytosine residues in single-stranded regions of polynucleotides.", "contents": "Reaction of cytidine with semicarbazide in the presence of bisulfite. A rapid modification specific for single-stranded polynucleotide. Semicarbazide reacted rapidly with 5,6-dihydrocytidine-6-sulfonate, which was formed from cytidine by addition of bisulfite across the 5,6-double bond. The transaminated product, 5,6-dihydro-4-semicarbazido-2-ketotopyrimidine-6-sulfonate ribofuranoside, was identified by comparison with that formed by treatment of 4-semicarbazido-2-ketopyrimidine ribofuranoside with bisulfite. The progress of the transamination was monitored spectrophotometrically by use of a strong absorbance of the product in alkali. The reaction between cytidine and the semicarbazide-bisulfite mixture was optimal at pH 4.5. Complete transformation of cytidine into the product required only 5 min with the use of 3M semicarbazide-1M sodium bisulfite, pH 5.0, at the reaction temperature 37 degrees C. The product was stable in unbuffered solution but in phosphate buffers it underwent elimination of bisulfite to give 4-semicarbazido-2-ketopyrimidine ribofuranoside. The rate of the elimination at pH 7.0 and 37 degrees C increased proportionally with the increase of the phosphate concentration. Complete elimination was obtained by treatment with 1 M sodium phosphate for 2 h. When heat-denatured calf-thymus DNA was treated with 3 M semicarbazide-1 M bisulfite at 37 degrees C and pH 5.0 the transamination of reactive cytosine residues was completed by 10 min of incubation. At 20 degrees C, it required 85 min of incubation. Cytosine residues in native DNA did not react at all even by prolonged incubations. The modified DNA samples were further treated with a phosphate buffer at pH 7, producing 4-semicarbazido-2-ketopyrimidine residues in the DNA. Analysis of the base compositions of these samples by perchloric acid hydrolysis showed that the modification was selective to cytosine, which had been expected from studies with monomers. It also showed that the reactive cytosine residues in the denatured DNA, constitute about 80% of the total cytosine, which was consistent with the view that heat-denatured DNA still contains a considerable amount of secondary structure. The semicarbazide-bisulfite modification is expected to be a sensitive method to locate cytosine residues in single-stranded regions of polynucleotides."}
{"id": "PMID:7289", "title": "Effects of substrate and inhibitor binding on thermal and proteolytic inactivation of rat liver transhydrogenase.", "content": "The thermostability and proteolytic inactivation of rat liver submitochondrial particle transhydrogenase was studied in the presence of pyridine dinucleotide substrates and a variety of divalent metal and nucleotide inhibitors. Relative to the unliganded enzyme, the NADPH-enzyme complex was more thermostable and showed a twofold greater rate of tryptic inactivation, while the NADP+-enzyme complex was more thermolabile and only slightly more susceptible to tryptic inactivation. Neither NAD+ nor NADH significantly affected thermostability or proteolysis. Similar effects of these ligands were observed for the non-energy-linked and energy-linked transhydrogenase reactions, indicating that both activities are catalyzed by the same enzyme. In thermal experiments, acetyl-CoA, 2'-AMP, and NMNH stabilized, palmitoyl-CoAlabilized, and dephospho-CoA, CoA, NMN+, and 5'-AMP had little effect on enzyme stability. Tryptic inactivation was inhibited by 2'-AMP and NMN+ but was not influenced by the other nucleotide inhibitors. Divalent metal ion inhibitors (Mg2+, Ca2+, Mn2+, Ba2+, and Sr2+) stabilized transhydrogenase against thermal inactivation and promoted tryptic inactivation.", "contents": "Effects of substrate and inhibitor binding on thermal and proteolytic inactivation of rat liver transhydrogenase. The thermostability and proteolytic inactivation of rat liver submitochondrial particle transhydrogenase was studied in the presence of pyridine dinucleotide substrates and a variety of divalent metal and nucleotide inhibitors. Relative to the unliganded enzyme, the NADPH-enzyme complex was more thermostable and showed a twofold greater rate of tryptic inactivation, while the NADP+-enzyme complex was more thermolabile and only slightly more susceptible to tryptic inactivation. Neither NAD+ nor NADH significantly affected thermostability or proteolysis. Similar effects of these ligands were observed for the non-energy-linked and energy-linked transhydrogenase reactions, indicating that both activities are catalyzed by the same enzyme. In thermal experiments, acetyl-CoA, 2'-AMP, and NMNH stabilized, palmitoyl-CoAlabilized, and dephospho-CoA, CoA, NMN+, and 5'-AMP had little effect on enzyme stability. Tryptic inactivation was inhibited by 2'-AMP and NMN+ but was not influenced by the other nucleotide inhibitors. Divalent metal ion inhibitors (Mg2+, Ca2+, Mn2+, Ba2+, and Sr2+) stabilized transhydrogenase against thermal inactivation and promoted tryptic inactivation."}
{"id": "PMID:7290", "title": "N-(1-pyrene)maleimide: a fluorescent cross-linking reagent.", "content": "N-(1-Pyrene)maleimide is nonfluorescent in aqueous solution but forms strongly fluorescent adducts with sulfhydryl groups of organic compounds or proteins. The conjugation reactions of N-(1-pyrene)maleimide are relatively fast and can be monitored by the increase in fluorescence intensity of the pyrene chromophore. In cases where primary amino groups are also present in the system, we have observed a red shift of the emission spectra of the fluorescent adducts subsequent to the initial conjugation, as characterized by the disappearance of three emission peaks at 376, 396, and 416 nm, and the appearance of two new peaks at 386 and 405 nm. Model studies with N-(1-pyrene)maleimide adducts of L-cysteine and cysteamine indicate that the spectral shift is the result of an intramolecular aminolysis of the succinimido ring in the adducts. Evidence from both chemical analysis and nuclear magnetic resonance studies of the addition products supports this reaction scheme. N-(1-Pyrene)maleimide adducts of N-acetyl-L-cysteine and beta-mercaptoethanol, which have no free amino group, do not exhibit a spectral shift. Among several protein conjugates only the N-(1-pyrene)maleimide adduct of bovine serum albumin (PM-BSA) shows the spectral shift resembling that of PM-cysteine. N-(1-Pyrene)maleimide reacts with the sulfhydryl group of the single cysteine residue at position 34 in BSA. The finding that the alpha-amino group of the N-terminus in PM-BSA is blocked after the spectral shift is completed strongly suggests that N-(1-pyrene)maleimide cross-links the N-terminus and the cysteine residue in BSA. The relative proximity of the sulfhydryl and amino groups is very critical in the cross-linking as demonstrated by the observation that the spectral shift observed with PM-BSA can be prevented by addition of denaturing reagents such as 1% sodium dodecyl sulfate immediately after labeling, and by the failure of PM-glutathione to undergo the intramolecular aminolysis. Since the intramolecular rearrangement of PM adducts is associated with characteristic fluorescence changes, N-(1-pyrene)maleimide can serve as a fluorescent cross-linking reagent which provides information about the spatial proximity of sulfhydryl and amino groups in proteins.", "contents": "N-(1-pyrene)maleimide: a fluorescent cross-linking reagent. N-(1-Pyrene)maleimide is nonfluorescent in aqueous solution but forms strongly fluorescent adducts with sulfhydryl groups of organic compounds or proteins. The conjugation reactions of N-(1-pyrene)maleimide are relatively fast and can be monitored by the increase in fluorescence intensity of the pyrene chromophore. In cases where primary amino groups are also present in the system, we have observed a red shift of the emission spectra of the fluorescent adducts subsequent to the initial conjugation, as characterized by the disappearance of three emission peaks at 376, 396, and 416 nm, and the appearance of two new peaks at 386 and 405 nm. Model studies with N-(1-pyrene)maleimide adducts of L-cysteine and cysteamine indicate that the spectral shift is the result of an intramolecular aminolysis of the succinimido ring in the adducts. Evidence from both chemical analysis and nuclear magnetic resonance studies of the addition products supports this reaction scheme. N-(1-Pyrene)maleimide adducts of N-acetyl-L-cysteine and beta-mercaptoethanol, which have no free amino group, do not exhibit a spectral shift. Among several protein conjugates only the N-(1-pyrene)maleimide adduct of bovine serum albumin (PM-BSA) shows the spectral shift resembling that of PM-cysteine. N-(1-Pyrene)maleimide reacts with the sulfhydryl group of the single cysteine residue at position 34 in BSA. The finding that the alpha-amino group of the N-terminus in PM-BSA is blocked after the spectral shift is completed strongly suggests that N-(1-pyrene)maleimide cross-links the N-terminus and the cysteine residue in BSA. The relative proximity of the sulfhydryl and amino groups is very critical in the cross-linking as demonstrated by the observation that the spectral shift observed with PM-BSA can be prevented by addition of denaturing reagents such as 1% sodium dodecyl sulfate immediately after labeling, and by the failure of PM-glutathione to undergo the intramolecular aminolysis. Since the intramolecular rearrangement of PM adducts is associated with characteristic fluorescence changes, N-(1-pyrene)maleimide can serve as a fluorescent cross-linking reagent which provides information about the spatial proximity of sulfhydryl and amino groups in proteins."}
{"id": "PMID:7291", "title": "Analysis of the interaction of organic phosphates with hemoglobin.", "content": "The interaction of organic phosphates with hemoglobin is studied by use of a simple thermodynamic approach. A model-independent analysis is employed to evaluate the accuracy of Adair constants determined in the presence of 2,3-diphosphoglycerate (DPG). The change of oxygen affinity in the presence of phosphates is related to the macroscopic phosphate binding constants of oxy- and deoxyhemoglobin and used to extract such binding constants from oxygen equilibrium measurements. The change of the Bohr effect in the presence of phosphates and the competitive binding of carbon dioxide and DPG are treated quantitatively. The binding of organic phosphates is incorporated into an allosteric model, in which the effect of phosphate on both tertiary and quaternary structure changes is included. By use of this model, the factors which can be responsible for the increased functional heterogeneity of alpha and beta chains in the presence of phosphates are clarified.", "contents": "Analysis of the interaction of organic phosphates with hemoglobin. The interaction of organic phosphates with hemoglobin is studied by use of a simple thermodynamic approach. A model-independent analysis is employed to evaluate the accuracy of Adair constants determined in the presence of 2,3-diphosphoglycerate (DPG). The change of oxygen affinity in the presence of phosphates is related to the macroscopic phosphate binding constants of oxy- and deoxyhemoglobin and used to extract such binding constants from oxygen equilibrium measurements. The change of the Bohr effect in the presence of phosphates and the competitive binding of carbon dioxide and DPG are treated quantitatively. The binding of organic phosphates is incorporated into an allosteric model, in which the effect of phosphate on both tertiary and quaternary structure changes is included. By use of this model, the factors which can be responsible for the increased functional heterogeneity of alpha and beta chains in the presence of phosphates are clarified."}
{"id": "PMID:7292", "title": "15N nuclear magnetic resonance of flavins.", "content": "Ninety-nine percent 15N-enriched flavins were synthesized and their proton decoupled 15N resonances were observed. The enriched compounds were [1,3-15N]riboflavin, [1,3,5-15N]riboflavin, [1,3-15N]riboflavin 5'-phosphate, [1,3,5-15N]riboflavin 5'-phosphate, and [1,3,5-15N] flavin adenine dinucleotide, [1,3,5-15N] lumiflavin, and [1,3,5-15N] lumichrome. By comparison of their spectra and from th- nuclear Overhauser effect data each 15N resonance peak could be assigned to each 15N nucleus. The order of the chemical shifts well corresponds to that of the calculated pi-electron densities. The N-3 nucleus gives the most intense inverted peak and the N-5 nucleus a small noninverted peak. By changing pH from neutral to alkaline, the chemical shift and the intensity of signal were mostly affected in the N-3 resonance of riboflavin 5'-phosphate. The N-5 signal of flavin adenine dinucleotide showed a fairly large downfield shift with the increase of temperature. These observations can be well interpreted by the chemical structure and the proposed conformation of riboflavin 5'-phosphate and flavin adenine dinucleotide.", "contents": "15N nuclear magnetic resonance of flavins. Ninety-nine percent 15N-enriched flavins were synthesized and their proton decoupled 15N resonances were observed. The enriched compounds were [1,3-15N]riboflavin, [1,3,5-15N]riboflavin, [1,3-15N]riboflavin 5'-phosphate, [1,3,5-15N]riboflavin 5'-phosphate, and [1,3,5-15N] flavin adenine dinucleotide, [1,3,5-15N] lumiflavin, and [1,3,5-15N] lumichrome. By comparison of their spectra and from th- nuclear Overhauser effect data each 15N resonance peak could be assigned to each 15N nucleus. The order of the chemical shifts well corresponds to that of the calculated pi-electron densities. The N-3 nucleus gives the most intense inverted peak and the N-5 nucleus a small noninverted peak. By changing pH from neutral to alkaline, the chemical shift and the intensity of signal were mostly affected in the N-3 resonance of riboflavin 5'-phosphate. The N-5 signal of flavin adenine dinucleotide showed a fairly large downfield shift with the increase of temperature. These observations can be well interpreted by the chemical structure and the proposed conformation of riboflavin 5'-phosphate and flavin adenine dinucleotide."}
{"id": "PMID:7293", "title": "Dual divalent cation requirement for activation of pyruvate kinase; essential roles of both enzyme- and nucleotide-bound metal ions.", "content": "Rabbit muscle pyruvate kinase requires two divalent cations per active site for catalysis of the enolization of pyruvate in the presence of adenosine 5'-triphosphate (ATP). One divalent cation is bound directly to the enzyme and forms a second sphere complex with the bound ATP (site 1). The second divalent cation is directly coordinated to the phosphoryl groups of ATP and does not interact with the enzyme (site 2). The essential role of the divalent cation at site 1 is shown by the requirement for Mg2+ or Mn2+ for the enolization of pyruvate in the presence of the substitution inert Cr3+-ATP complex. The rate of detritiation of pyruvate shows a hyperbolic dependence of Mn2+ concentration in the presence of high concentrations of enzyme and Cr3+-ATP. A dissociation constant for Mn2+ from the pyruvate kinase-Mn2+-ATP-Cr3+-pyruvate complex of 1.3 +/- 0.5 muM is determined by the kinetics of detritiation of pyruvate and by parallel Mn2+ binding studies using electron paramagnetic resonance. The essential role of the divalent cation at site 2 is shown by the sigmoidal dependence of the rate of detritiation of pyruvate on Mn2+ concentration in the presence of high concentrations of enzyme and ATP yielding a dissociation constant of 29 +/- 9 muM for Mn2+ from site 2. This value is similar to the dissociation constant of the binary Mn-ATP complex (14 +/- 6 muM) determined under similar conditions. The rate of detritiation of pyruvate is proportional to the concentration of the pyruvate kinase-Mn2+-ATP-Mn2+-pyruvate complex, as determined by parellel kinetic and binding studies. Variation of the nature of the divalent cation at site 1 in the presence of CrATP causes only a twofold change in the rate of detritiation of pyruvate which does not correlate with the pKa of the metal-bound water. Variation of the nature of the divalent cation at both sites in the presence of ATP causes a sevenfold variation in the rate of detritiation or pyruvate that correlates with the pKa of the metal-bound water. The greater rate of enolization observed with CrATP fits this correlation, indicating that the electrophilicity of the nucleotide bound metal (at site 2) determines the rate of enolization of pyruvate.", "contents": "Dual divalent cation requirement for activation of pyruvate kinase; essential roles of both enzyme- and nucleotide-bound metal ions. Rabbit muscle pyruvate kinase requires two divalent cations per active site for catalysis of the enolization of pyruvate in the presence of adenosine 5'-triphosphate (ATP). One divalent cation is bound directly to the enzyme and forms a second sphere complex with the bound ATP (site 1). The second divalent cation is directly coordinated to the phosphoryl groups of ATP and does not interact with the enzyme (site 2). The essential role of the divalent cation at site 1 is shown by the requirement for Mg2+ or Mn2+ for the enolization of pyruvate in the presence of the substitution inert Cr3+-ATP complex. The rate of detritiation of pyruvate shows a hyperbolic dependence of Mn2+ concentration in the presence of high concentrations of enzyme and Cr3+-ATP. A dissociation constant for Mn2+ from the pyruvate kinase-Mn2+-ATP-Cr3+-pyruvate complex of 1.3 +/- 0.5 muM is determined by the kinetics of detritiation of pyruvate and by parallel Mn2+ binding studies using electron paramagnetic resonance. The essential role of the divalent cation at site 2 is shown by the sigmoidal dependence of the rate of detritiation of pyruvate on Mn2+ concentration in the presence of high concentrations of enzyme and ATP yielding a dissociation constant of 29 +/- 9 muM for Mn2+ from site 2. This value is similar to the dissociation constant of the binary Mn-ATP complex (14 +/- 6 muM) determined under similar conditions. The rate of detritiation of pyruvate is proportional to the concentration of the pyruvate kinase-Mn2+-ATP-Mn2+-pyruvate complex, as determined by parellel kinetic and binding studies. Variation of the nature of the divalent cation at site 1 in the presence of CrATP causes only a twofold change in the rate of detritiation of pyruvate which does not correlate with the pKa of the metal-bound water. Variation of the nature of the divalent cation at both sites in the presence of ATP causes a sevenfold variation in the rate of detritiation or pyruvate that correlates with the pKa of the metal-bound water. The greater rate of enolization observed with CrATP fits this correlation, indicating that the electrophilicity of the nucleotide bound metal (at site 2) determines the rate of enolization of pyruvate."}
{"id": "PMID:7294", "title": "NADP+ and NADPH in glucose-6-phosphate dehydrogenase-deficient erythrocytes under oxidative stimulation.", "content": "A mild oxidative stimulation of the hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49)-deficient erythrocytes (Mediterranean variant) causes a significant drop in NADPH. These results, other than to confirm that glucose-6-phosphate dehydrogenase deficiency is a product deficiency disorder, demonstrate that under oxidative stimulation glutathione reductase may become functionally impaired and GSSG cannot be reduced at a sufficient rate.", "contents": "NADP+ and NADPH in glucose-6-phosphate dehydrogenase-deficient erythrocytes under oxidative stimulation. A mild oxidative stimulation of the hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49)-deficient erythrocytes (Mediterranean variant) causes a significant drop in NADPH. These results, other than to confirm that glucose-6-phosphate dehydrogenase deficiency is a product deficiency disorder, demonstrate that under oxidative stimulation glutathione reductase may become functionally impaired and GSSG cannot be reduced at a sufficient rate."}
{"id": "PMID:7295", "title": "Purification and properties of ATPase inhibitor from rat liver mitochondria.", "content": "(1) The ATPase inhibitior protein has been isolated from rat liver mitochondria in purified form. The molecular weight determined by sodium dodecyl sulfate gel electrophoresis is approximately 9500, and the isoelectric point is 8.9. (2) The protein inhibits both the soluble ATPase and the particle-bound ATPase from rat liver mitochondria. It also inhibits ATPase activities of soluble F1, and inhibitor-depleted submitochondrial particles derived from bovine heart mitochondria. (3) On particle-bound ATPase the inhibitor has its maximal effect if incubated in the presence of Mg2+. ATP at slightly acidic pH. (4) The inhibitor has a minimal effect on Pi-ATP exchange activity in sonicated submitochondrial particles. However, unexpectedly the inhibitor greatly stimules Pi-ATP exchange activity in whole mitochondria while the low ATPase activity of the mitochondria is not affected. The possible mechanism of action of the  inhibitor on intact mitochondria is offered.", "contents": "Purification and properties of ATPase inhibitor from rat liver mitochondria. (1) The ATPase inhibitior protein has been isolated from rat liver mitochondria in purified form. The molecular weight determined by sodium dodecyl sulfate gel electrophoresis is approximately 9500, and the isoelectric point is 8.9. (2) The protein inhibits both the soluble ATPase and the particle-bound ATPase from rat liver mitochondria. It also inhibits ATPase activities of soluble F1, and inhibitor-depleted submitochondrial particles derived from bovine heart mitochondria. (3) On particle-bound ATPase the inhibitor has its maximal effect if incubated in the presence of Mg2+. ATP at slightly acidic pH. (4) The inhibitor has a minimal effect on Pi-ATP exchange activity in sonicated submitochondrial particles. However, unexpectedly the inhibitor greatly stimules Pi-ATP exchange activity in whole mitochondria while the low ATPase activity of the mitochondria is not affected. The possible mechanism of action of the  inhibitor on intact mitochondria is offered."}
{"id": "PMID:7296", "title": "[Photosensitization of consitutents of nucleic acids by proflavine. Mechanism of formation of hydrogen addition radicals in frozen aquenous solutions (author's transl)].", "content": "It is shown that the insertion of nucleotides between proflavine molecules is favourable to photosensitization. Furthermore (1) each molecule of proflavine gives at the most one free radical in the substrate, (2) the chromophore is largely restored when oxygen is not present, (3) superoxide radicals are observed in the presence of oxygen, and (4) formyl radicals are detected. The scheme elaborated for the mechanism gives an explanation for all these observations.", "contents": "[Photosensitization of consitutents of nucleic acids by proflavine. Mechanism of formation of hydrogen addition radicals in frozen aquenous solutions (author's transl)]. It is shown that the insertion of nucleotides between proflavine molecules is favourable to photosensitization. Furthermore (1) each molecule of proflavine gives at the most one free radical in the substrate, (2) the chromophore is largely restored when oxygen is not present, (3) superoxide radicals are observed in the presence of oxygen, and (4) formyl radicals are detected. The scheme elaborated for the mechanism gives an explanation for all these observations."}
{"id": "PMID:7297", "title": "NADPH/NADP+ ratios in photosynthesizing reconstituted chloroplasts.", "content": "Levels of reduced and oxidized triphosphopyridine nucleotides have been determined in reconstituted spinach chloroplasts and compared with levels in whole isolated chloroplasts during photosynthesis and darkness. The ratio of NADPH/NADP+ reaches values slightly above 1.0 at the beginning of photosynthesis, less than half the ratio attained with whole chloroplasts. Nonetheless these lower ratios are sufficient to maintain high rates of photosynthetic carbon dioxide fixation and reduction, which are comparable in the reconstituted chloroplasts to the rates found with whole chloroplasts. As with whole chloroplasts there is a decline in the ration of NADPH/NADP+ as a function of time of photosynthesis. The effect of addition of bicarbonate (6 mM) in causing a transient drop in the ratio of NADPH/NADP/ is described and discussed in terms of the reversibility of the reduction of 3-phosphoglycerate to triose phosphate. The ratio NADPH/NADP+ can be improved by the addition of more lamellae either before or during the course of photosynthesis, and this improvement in ratio is accompanied by an improved rate of CO2 fixation or a more sustained rate of CO2 fixation with time of photosynthesis. The importance of NADPH/NADP+ ratio not only to the reduction of 3-phosphoglycerate to triose phosphate but also to the activation of the ribulose-1,5-diphosphate carboxylasemediated step is discussed.", "contents": "NADPH/NADP+ ratios in photosynthesizing reconstituted chloroplasts. Levels of reduced and oxidized triphosphopyridine nucleotides have been determined in reconstituted spinach chloroplasts and compared with levels in whole isolated chloroplasts during photosynthesis and darkness. The ratio of NADPH/NADP+ reaches values slightly above 1.0 at the beginning of photosynthesis, less than half the ratio attained with whole chloroplasts. Nonetheless these lower ratios are sufficient to maintain high rates of photosynthetic carbon dioxide fixation and reduction, which are comparable in the reconstituted chloroplasts to the rates found with whole chloroplasts. As with whole chloroplasts there is a decline in the ration of NADPH/NADP+ as a function of time of photosynthesis. The effect of addition of bicarbonate (6 mM) in causing a transient drop in the ratio of NADPH/NADP/ is described and discussed in terms of the reversibility of the reduction of 3-phosphoglycerate to triose phosphate. The ratio NADPH/NADP+ can be improved by the addition of more lamellae either before or during the course of photosynthesis, and this improvement in ratio is accompanied by an improved rate of CO2 fixation or a more sustained rate of CO2 fixation with time of photosynthesis. The importance of NADPH/NADP+ ratio not only to the reduction of 3-phosphoglycerate to triose phosphate but also to the activation of the ribulose-1,5-diphosphate carboxylasemediated step is discussed."}
{"id": "PMID:7298", "title": "Long-term regulation by theophylline of fatty acid synthetase, acetyl-CoA carboxylase and lipid synthesis in cultured glial cells.", "content": "The long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase and of fatty acid and sterol synthesis was studied in C-6 glial cells in culture. When theophylline (10(-3) M) was added to the culture medium of these cells, rates of lipid synthesis from acetate and activities of synthetase and carboxylase became distinctly lower than in cells that were untreated. This effect appeared after approximately 12 h, and after 48 h enzymatic activities were reduced approx. 2-fold and rates of lipid synthesis from acetate 3- to 4-fold. The likelihood that the decrease in fatty acid synthesis from acetate was caused by the decrease in activities of fatty acid synthetase and acetyl-CoA carboxylase was established by several observations. These indicated that the locus of the effect probably did not reside at the level of acetate uptake into the cell, alterations in acetate pool sizes or conversion of acetate to acetyl-CoA. Moreover, de novo fatty acid synthesis was found to be the predominant pathway in these glial cells, whether treated with theophylline or not. The mechanism of the effect of theophylline on fatty acid synthetase was shown by immunochemical techniques to involve an alteration in content of enzyme rather than in catalytic efficiency. The change in content of fatty acid synthetase was shown by isotopic-immunochemical experiments to involve a decrease in synthesis of the enzyme. The mechanism whereby theophylline leads to a decrease in lipogenesis and in the synthesis of fatty acid synthetase may not be mediated entirely by inhibition of phosphodiesterase and an increase in cyclic AMP levels, because dibutyryl cyclic AMP (10(-3) M) only partially reproduced the effect.", "contents": "Long-term regulation by theophylline of fatty acid synthetase, acetyl-CoA carboxylase and lipid synthesis in cultured glial cells. The long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase and of fatty acid and sterol synthesis was studied in C-6 glial cells in culture. When theophylline (10(-3) M) was added to the culture medium of these cells, rates of lipid synthesis from acetate and activities of synthetase and carboxylase became distinctly lower than in cells that were untreated. This effect appeared after approximately 12 h, and after 48 h enzymatic activities were reduced approx. 2-fold and rates of lipid synthesis from acetate 3- to 4-fold. The likelihood that the decrease in fatty acid synthesis from acetate was caused by the decrease in activities of fatty acid synthetase and acetyl-CoA carboxylase was established by several observations. These indicated that the locus of the effect probably did not reside at the level of acetate uptake into the cell, alterations in acetate pool sizes or conversion of acetate to acetyl-CoA. Moreover, de novo fatty acid synthesis was found to be the predominant pathway in these glial cells, whether treated with theophylline or not. The mechanism of the effect of theophylline on fatty acid synthetase was shown by immunochemical techniques to involve an alteration in content of enzyme rather than in catalytic efficiency. The change in content of fatty acid synthetase was shown by isotopic-immunochemical experiments to involve a decrease in synthesis of the enzyme. The mechanism whereby theophylline leads to a decrease in lipogenesis and in the synthesis of fatty acid synthetase may not be mediated entirely by inhibition of phosphodiesterase and an increase in cyclic AMP levels, because dibutyryl cyclic AMP (10(-3) M) only partially reproduced the effect."}
{"id": "PMID:7299", "title": "Involvement of a single hydroxylase species in the hydroxylation of palmitate at the omega-1, omega-2 and omega-3 positions by a preparation from Bacillus megaterium.", "content": "A soluble enzyme preparation from Bacillus megaterium, requiring NADPH and O2 for activity and containing ferredoxin-replaceable and cytochrome P-450-type components, was previously shown to catalyze the conversion of palmitic acid to an isomeric mixture of omega-1, omega-2 and omega-3 hydroxypalmitate. It has now been shown that the ratio of these three positional isomers in the enzymatic product remains unchanged in spite of partial diminution of total hydroxylase activity by heat treatment, pH change or inhibition by p-hydroxy-mercuribenzoate or carbon monoxide. These findings strongly support the hypothesis that a single hydroxylase with one substrate binding site is responsible for hydroxylation at all three positions of palmitate.", "contents": "Involvement of a single hydroxylase species in the hydroxylation of palmitate at the omega-1, omega-2 and omega-3 positions by a preparation from Bacillus megaterium. A soluble enzyme preparation from Bacillus megaterium, requiring NADPH and O2 for activity and containing ferredoxin-replaceable and cytochrome P-450-type components, was previously shown to catalyze the conversion of palmitic acid to an isomeric mixture of omega-1, omega-2 and omega-3 hydroxypalmitate. It has now been shown that the ratio of these three positional isomers in the enzymatic product remains unchanged in spite of partial diminution of total hydroxylase activity by heat treatment, pH change or inhibition by p-hydroxy-mercuribenzoate or carbon monoxide. These findings strongly support the hypothesis that a single hydroxylase with one substrate binding site is responsible for hydroxylation at all three positions of palmitate."}
{"id": "PMID:7300", "title": "Purification and properties of two lipases from pig adipose tissue.", "content": "Two lipases were purified from pig adipose tissue after delipidation by a mild and effective procedure using mixtures of chloroform and butanol. This was followed by hydrophobic adsorption chromatography on aminohexyl-Sepharose 4B coupled with octanoic acid, gel filtration on Sephadex G-100, and isoelectric focusing. Two electrophoretically and chromatographically pure enzymes were obtained, which had the same molecular weight (60 000 +/- 3000) and specific activity, and almost identical amino acid compositions; the isoelectric points, i.e. 5.2 and 5.5, differed.", "contents": "Purification and properties of two lipases from pig adipose tissue. Two lipases were purified from pig adipose tissue after delipidation by a mild and effective procedure using mixtures of chloroform and butanol. This was followed by hydrophobic adsorption chromatography on aminohexyl-Sepharose 4B coupled with octanoic acid, gel filtration on Sephadex G-100, and isoelectric focusing. Two electrophoretically and chromatographically pure enzymes were obtained, which had the same molecular weight (60 000 +/- 3000) and specific activity, and almost identical amino acid compositions; the isoelectric points, i.e. 5.2 and 5.5, differed."}
{"id": "PMID:7301", "title": "Estrogen biosynthesis and 1beta-hydroxylation using C19 and 19-nor steroid precursors.", "content": "(1) In order to study the relationship between aromatization (estrogen biosynthesis) and 1beta-hydroxylation, the effects of a variety of factors on these processes were evaluated. (2) Using the C18 substrate, 4-estrene-3,17-dione, it was found that carbon monoxide, SU-4885, amphenone B, potassium cyanide, 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione inhibited the above transformations significantly and to varying degrees. However, within a given experiment the inhibition of each process was similar. (3) SKF-525A did not inhibit either transformation. In addition, phosphate, Tris and barbital buffers, as well as pH changes from 6.9 to 7.7, had no stimulatory or inhibitory effect on the production of estrogen and 1beta-hydroxy compounds. (4) In contrast, several inhibitors affected the aromatization of C19 and C18 steroids differently. These include carbon monoxide, SU-4885 and amphenone B. (5) When a mixture of 4-[7beta-3Hi1estrene-3,17-dione and 19-[4-14C]nortestosterone were incubated together the former was preferentially converted to estrogen. This preference for the 17-keto steroidal form mimics results observed for C19 substrates. (6) We conclude that while estrogen biosynthesis and 1beta-hydroxylation appear to be mediated by the same enzyme system, the same conclusion cannot be drawn for the aromatization of C19 and C18 substrates.", "contents": "Estrogen biosynthesis and 1beta-hydroxylation using C19 and 19-nor steroid precursors. (1) In order to study the relationship between aromatization (estrogen biosynthesis) and 1beta-hydroxylation, the effects of a variety of factors on these processes were evaluated. (2) Using the C18 substrate, 4-estrene-3,17-dione, it was found that carbon monoxide, SU-4885, amphenone B, potassium cyanide, 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione inhibited the above transformations significantly and to varying degrees. However, within a given experiment the inhibition of each process was similar. (3) SKF-525A did not inhibit either transformation. In addition, phosphate, Tris and barbital buffers, as well as pH changes from 6.9 to 7.7, had no stimulatory or inhibitory effect on the production of estrogen and 1beta-hydroxy compounds. (4) In contrast, several inhibitors affected the aromatization of C19 and C18 steroids differently. These include carbon monoxide, SU-4885 and amphenone B. (5) When a mixture of 4-[7beta-3Hi1estrene-3,17-dione and 19-[4-14C]nortestosterone were incubated together the former was preferentially converted to estrogen. This preference for the 17-keto steroidal form mimics results observed for C19 substrates. (6) We conclude that while estrogen biosynthesis and 1beta-hydroxylation appear to be mediated by the same enzyme system, the same conclusion cannot be drawn for the aromatization of C19 and C18 substrates."}
{"id": "PMID:7302", "title": "A sulfonolipid and novel glucosamidyl glycolipids from the extreme thermoacidophile Bacillus acidocaldarius.", "content": "The total lipid content of the extreme thermoacidophile Bacillus acidocaldarius comprises about 8.1% of the cell dry weight. Total lipid had a distribution of 15.7% neutral linique component initially characterized as an N-acylglucosamine beta-linked to the primary hydroxyl of an unusual fully saturated pentacyclic triterpene derived tetrol(C35H62O4, Mr 546), which appears to be a derivative of the pentacylcic triterpene hopane substituted at C-29 with a 1,2,3,4-tetrahydroxy pentane. Other major glycolipids present were partially characterized as O-beta-D-glucopyranosyl-(1 leads to 4)-O-2-acylamido-2-deoxy-beta D-glucopyranosyldiacylglycerol and O-beta-D-glucopyranosyl-(1 leads to 4)-O-2-acylamido-2-deoxy-beta-D-glucopyranosylmonoacylglycerol. Minor components of the glycolipid fraction included O-beta-D-glucopyranosyl-(1 leads to 4)-O-2-acylamido-2-deoxy-beta-D-glucopyranosylglycerol, O-2-amino-2-deoxy-beta-D-glucopyranosyl pentacyclic tetrol and free pentacyclic tetrol. The distributions of esterified and amide-linked fatty acids were similar, being comprised primarily of branched heptadecanoic, 11-cyclohexyundecanoic and 13-cyclohexyltridecanoic acids. The acid lipids were composed of a sulfonoglycosyldiacylglycerol (43.2%), diphosphatidylglycerol (32.3%), lysodiphosphatidylglycerol (5.3%), phosphatidic acid (5.8%) and phosphatidylglycerol (13.4%).", "contents": "A sulfonolipid and novel glucosamidyl glycolipids from the extreme thermoacidophile Bacillus acidocaldarius. The total lipid content of the extreme thermoacidophile Bacillus acidocaldarius comprises about 8.1% of the cell dry weight. Total lipid had a distribution of 15.7% neutral linique component initially characterized as an N-acylglucosamine beta-linked to the primary hydroxyl of an unusual fully saturated pentacyclic triterpene derived tetrol(C35H62O4, Mr 546), which appears to be a derivative of the pentacylcic triterpene hopane substituted at C-29 with a 1,2,3,4-tetrahydroxy pentane. Other major glycolipids present were partially characterized as O-beta-D-glucopyranosyl-(1 leads to 4)-O-2-acylamido-2-deoxy-beta D-glucopyranosyldiacylglycerol and O-beta-D-glucopyranosyl-(1 leads to 4)-O-2-acylamido-2-deoxy-beta-D-glucopyranosylmonoacylglycerol. Minor components of the glycolipid fraction included O-beta-D-glucopyranosyl-(1 leads to 4)-O-2-acylamido-2-deoxy-beta-D-glucopyranosylglycerol, O-2-amino-2-deoxy-beta-D-glucopyranosyl pentacyclic tetrol and free pentacyclic tetrol. The distributions of esterified and amide-linked fatty acids were similar, being comprised primarily of branched heptadecanoic, 11-cyclohexyundecanoic and 13-cyclohexyltridecanoic acids. The acid lipids were composed of a sulfonoglycosyldiacylglycerol (43.2%), diphosphatidylglycerol (32.3%), lysodiphosphatidylglycerol (5.3%), phosphatidic acid (5.8%) and phosphatidylglycerol (13.4%)."}
{"id": "PMID:7303", "title": "A 1,2,3,4-tetrahydroxy pentane-substituted pentacyclic triterpene from Bacillus acidocaldarius.", "content": "A long-chained polyalcohol (polyol) was isolated from the glycolipid fraction of the extreme thermoacidophile Bacillus acidocaldarius. The polyol and its Smith degradation products, as well as the alkanes derived from these compounds were characterized by mobility on thin-layer and gas-liquid chromatography, and by infrared and mass spectrometry. The polyol is proposed to be a fully saturated pentacyclic tetrol (C35H62O4, Mr 546) containing a 1,2,3,4-tetrahydroxy pentane substituted to a hopane-derived pentacyclic triterpene nucleus.", "contents": "A 1,2,3,4-tetrahydroxy pentane-substituted pentacyclic triterpene from Bacillus acidocaldarius. A long-chained polyalcohol (polyol) was isolated from the glycolipid fraction of the extreme thermoacidophile Bacillus acidocaldarius. The polyol and its Smith degradation products, as well as the alkanes derived from these compounds were characterized by mobility on thin-layer and gas-liquid chromatography, and by infrared and mass spectrometry. The polyol is proposed to be a fully saturated pentacyclic tetrol (C35H62O4, Mr 546) containing a 1,2,3,4-tetrahydroxy pentane substituted to a hopane-derived pentacyclic triterpene nucleus."}
{"id": "PMID:7304", "title": "An investigation of an unusual histidyl residue in Escherichia coli B L-asparaginase through fluorescence quenching.", "content": "The tryptophanyl fluorescence of Escherichia coli B L-asparaginase is partially quenched by the protonated form of a base with pKa 6.0 at 25 degrees C, mu = 0.1. This base has been identified as a histidyl residue through the effect of ionic strength and solvent polarity on the pKa. In addition diethylpyrocarbonate which modifies two histidyl residues in the enzyme abolishes the fluorescenc titration and reduces enzymic activity by 90%. The temperature dependence of the histidine pKa is unusual, showing a minimum at 25 degrees C, a thermodynamic analysis of the data shows this to be due to a large negative delta Cp term associated with the ionisation. This is interpreted in terms of the movement of hydrophobic residues into the enzyme on deprotonation of the histidyl residue. The quantum yield of L-asparaginase and its temperature dependence have been measured. The quantum yield is high and there is a low activation energy for radiationless deactivation of the excited state both of which are consistent with a tryptophanyl environment remote from the solvent.", "contents": "An investigation of an unusual histidyl residue in Escherichia coli B L-asparaginase through fluorescence quenching. The tryptophanyl fluorescence of Escherichia coli B L-asparaginase is partially quenched by the protonated form of a base with pKa 6.0 at 25 degrees C, mu = 0.1. This base has been identified as a histidyl residue through the effect of ionic strength and solvent polarity on the pKa. In addition diethylpyrocarbonate which modifies two histidyl residues in the enzyme abolishes the fluorescenc titration and reduces enzymic activity by 90%. The temperature dependence of the histidine pKa is unusual, showing a minimum at 25 degrees C, a thermodynamic analysis of the data shows this to be due to a large negative delta Cp term associated with the ionisation. This is interpreted in terms of the movement of hydrophobic residues into the enzyme on deprotonation of the histidyl residue. The quantum yield of L-asparaginase and its temperature dependence have been measured. The quantum yield is high and there is a low activation energy for radiationless deactivation of the excited state both of which are consistent with a tryptophanyl environment remote from the solvent."}
{"id": "PMID:7305", "title": "Studies on camel hemoglobin. 1. Physico-chemical properties and some structural aspects of camel hemoglobin (Camelus dromedarius).", "content": "Hemoglobin from an adult camel (Camelus dromedarius) was prepared from the red cell lysate by CM- and DEAE-cellulose chromatography. The purified hemoglobin showed a lesser mobility on starch gel electrophoresis at pH 8.5 than that of human hemoglobin C. Native camel hemoglobin contains 95-99% alkali-resistant hemoglobin and in soluble in 2.94 M K2HPO4/KH2PO4 buffer. Different forms of camel hemoglobin show similar ammonium sulfate precipitation curves. Indirect evidence for the stability of camel hemoglobin solutions was obtained from several sources. Spontaneous met-hemoglobin formation is extremely slow and minimal quantities of degradation products appear on starch gel electrophoresis and on chromatographic separation. The alpha and beta chains of camel hemoglobin A were separated on a CM-23 column by the use of a pyridine formate gradient. Large peptide fragments were obtained by tryptic digestion of maleylated alpha and beta chains. The N-terminal structure of the alpha and beta chains and of tryptic maleylated peptides derived from alpha and beta chains are presented. Between adult camel hemoglobin and adult human hemoglobin six amino acid differences in the N-terminal 20 amino acid residues of the alpha chain, at residues: 4, 5, 12, 14, 17, and 19; eight amino acid substitutions were found in the beta chain at positions: 4, 5, 6, 9, 12, 13, 16, and 19. Substitutions at alpha5 Ala leads to Lys, and beta19 Asn leads to Lys, increase the net positive charge of camel hemoglobin by two, while other substitutions result in no charge differences. The molecular basis of the stability of camel adult hemoglobin is discussed.", "contents": "Studies on camel hemoglobin. 1. Physico-chemical properties and some structural aspects of camel hemoglobin (Camelus dromedarius). Hemoglobin from an adult camel (Camelus dromedarius) was prepared from the red cell lysate by CM- and DEAE-cellulose chromatography. The purified hemoglobin showed a lesser mobility on starch gel electrophoresis at pH 8.5 than that of human hemoglobin C. Native camel hemoglobin contains 95-99% alkali-resistant hemoglobin and in soluble in 2.94 M K2HPO4/KH2PO4 buffer. Different forms of camel hemoglobin show similar ammonium sulfate precipitation curves. Indirect evidence for the stability of camel hemoglobin solutions was obtained from several sources. Spontaneous met-hemoglobin formation is extremely slow and minimal quantities of degradation products appear on starch gel electrophoresis and on chromatographic separation. The alpha and beta chains of camel hemoglobin A were separated on a CM-23 column by the use of a pyridine formate gradient. Large peptide fragments were obtained by tryptic digestion of maleylated alpha and beta chains. The N-terminal structure of the alpha and beta chains and of tryptic maleylated peptides derived from alpha and beta chains are presented. Between adult camel hemoglobin and adult human hemoglobin six amino acid differences in the N-terminal 20 amino acid residues of the alpha chain, at residues: 4, 5, 12, 14, 17, and 19; eight amino acid substitutions were found in the beta chain at positions: 4, 5, 6, 9, 12, 13, 16, and 19. Substitutions at alpha5 Ala leads to Lys, and beta19 Asn leads to Lys, increase the net positive charge of camel hemoglobin by two, while other substitutions result in no charge differences. The molecular basis of the stability of camel adult hemoglobin is discussed."}
{"id": "PMID:7306", "title": "Magnetic circular dichroism of myoglobin-thiolate complexes.", "content": "Various complexes of myoglobin (Mb) with thiolate were studied by use of magnetic circular dichroism (MCD) spectroscopy. 1. MetMb-ethyl, n-propyl and isopropylmercaptan complexes offered MCD spectra similar to that of cytochrome P-450 (P-450) with respect to shape and intensity ratio of Soret MCD to Q0-0 MCD. The MCD spectra did not show any pH dependence. The complexes reduced by sodium dithionite exhibited the MCD spectrum of deoxyMb, indicative of release of thiolate anion from the heme iron. 2. Cysteine and cysteine methyl ester coordinated to the heme iron at pH 9.18 but not at pH 6.86 and 11.45. The complex formed at pH 9.18 gave an MCD spectrum similar to that of P-450, and an MCD spectrum of deoxy Mb on reduction with sodium dithionite. 3. The 2-mercaptoethanol complex exhibited three A terms associated with the Q0-0-1, and Soret transitions at pH 6.86 similar to those of Fe(II) cytochrome c, which indicates that Mb was reduced by this reagent at pH 6.86. At pH 9.18 2-mercaptoethanol gave an MCD spectrum similar to that of alkyl mercaptan just after the addition. With the time changed into deoxy Mb through some intermediate of reduced Mb-thiolate complex. At pH 11.45 2-mercaptoethanol formed complex which exhibited an MCD spectrum similar to those of other alkylmercaptans. 4. Sodium sulfide gave an MCD spectrum which resembled that of the normal thiol Mb complex just after addition at pH 6.86. The complex was gradually reduced to give 610 nm trough in addition to the MCD of deoxy Mb. The Mb-sulfur complex formed at pH 9.18 was gradually reduced to give an MCD spectrum which was fairly different from that of deoxy Mb. A similar MCD spectrum was observed at pH 11.45 just after the addition of Na2S. These results were considered to suggest the saturation of one of the conjugated double bonds of the porphyrin by sulfur.", "contents": "Magnetic circular dichroism of myoglobin-thiolate complexes. Various complexes of myoglobin (Mb) with thiolate were studied by use of magnetic circular dichroism (MCD) spectroscopy. 1. MetMb-ethyl, n-propyl and isopropylmercaptan complexes offered MCD spectra similar to that of cytochrome P-450 (P-450) with respect to shape and intensity ratio of Soret MCD to Q0-0 MCD. The MCD spectra did not show any pH dependence. The complexes reduced by sodium dithionite exhibited the MCD spectrum of deoxyMb, indicative of release of thiolate anion from the heme iron. 2. Cysteine and cysteine methyl ester coordinated to the heme iron at pH 9.18 but not at pH 6.86 and 11.45. The complex formed at pH 9.18 gave an MCD spectrum similar to that of P-450, and an MCD spectrum of deoxy Mb on reduction with sodium dithionite. 3. The 2-mercaptoethanol complex exhibited three A terms associated with the Q0-0-1, and Soret transitions at pH 6.86 similar to those of Fe(II) cytochrome c, which indicates that Mb was reduced by this reagent at pH 6.86. At pH 9.18 2-mercaptoethanol gave an MCD spectrum similar to that of alkyl mercaptan just after the addition. With the time changed into deoxy Mb through some intermediate of reduced Mb-thiolate complex. At pH 11.45 2-mercaptoethanol formed complex which exhibited an MCD spectrum similar to those of other alkylmercaptans. 4. Sodium sulfide gave an MCD spectrum which resembled that of the normal thiol Mb complex just after addition at pH 6.86. The complex was gradually reduced to give 610 nm trough in addition to the MCD of deoxy Mb. The Mb-sulfur complex formed at pH 9.18 was gradually reduced to give an MCD spectrum which was fairly different from that of deoxy Mb. A similar MCD spectrum was observed at pH 11.45 just after the addition of Na2S. These results were considered to suggest the saturation of one of the conjugated double bonds of the porphyrin by sulfur."}
{"id": "PMID:7307", "title": "Structural features of luliberin (luteinising hormone-releasing factor) inferred from fluorescence measurements.", "content": "The fluorescence and excitation spectra of luliberin (luteinizing hormone-releasing factor) in 0.005 M aqueous ammonium acetate are identical in shape to those of N-acetyltryptophan amide and are related to the indole side chain of Trp3. The change of fluoresecence intensity of luliberin with pH was measured in the range of pH 4-11. The increase of pH from 4 to 7.5 is followed by about 50% increase in fluorescence intensity due to deprotonation of the imidazolium side chain of His2. The fluorimetric titration curve in this pH region reveals a pK value for His2 of 5.95. Increasing of pH from 8 to 11 results in about 40% quenching of the fluorescence due to electronic energy transfer from the excited indole of Trp3 to the phenolate side chain of Tyr5. The pK value of Tyr5, obtained independently from the fluorimetric and photometric titrations indicate that at pH 7-8 luliberin contains only one charged residue, Arg8, which is in close vicinity to both His2 and Tyr5. The side chains of His2, Tyr5 and Arg8 presumably form a combined unit which may play an active role in the hormone action. Trp3 is at a maximal distance from this unit and may thus act as an independent active unit.", "contents": "Structural features of luliberin (luteinising hormone-releasing factor) inferred from fluorescence measurements. The fluorescence and excitation spectra of luliberin (luteinizing hormone-releasing factor) in 0.005 M aqueous ammonium acetate are identical in shape to those of N-acetyltryptophan amide and are related to the indole side chain of Trp3. The change of fluoresecence intensity of luliberin with pH was measured in the range of pH 4-11. The increase of pH from 4 to 7.5 is followed by about 50% increase in fluorescence intensity due to deprotonation of the imidazolium side chain of His2. The fluorimetric titration curve in this pH region reveals a pK value for His2 of 5.95. Increasing of pH from 8 to 11 results in about 40% quenching of the fluorescence due to electronic energy transfer from the excited indole of Trp3 to the phenolate side chain of Tyr5. The pK value of Tyr5, obtained independently from the fluorimetric and photometric titrations indicate that at pH 7-8 luliberin contains only one charged residue, Arg8, which is in close vicinity to both His2 and Tyr5. The side chains of His2, Tyr5 and Arg8 presumably form a combined unit which may play an active role in the hormone action. Trp3 is at a maximal distance from this unit and may thus act as an independent active unit."}
{"id": "PMID:7308", "title": "Non-heme iron proteins. The amino acid sequence of rubredoxin from Desulfovibrio vulgaris.", "content": "A non-heme iron protein, rubredoxin has been isolated from the sulfate-reducing bacterium, Desulfovibrio vulgaris, strain Hildenborough. The complete amino acid sequence has been established. The 52 amino acid residues of the protein were aligned with the aid of tryptic and chymotryptic peptides and of a fragment produced by cleavage of the Asn-Gly bond (22-23) by hydroxylamine. The sequence of the first 30 residues of the molecule was determined using an automatic sequenator, after removal of the N-terminal methionine by CNBr. In comparing this sequence with those of Micrococcus aerogenes, Clostridium pasteurianum and Peptostreptococcus elsdenii rubredoxins, a high degree of mutation was observed between these homologous proteins. It has been shown that 20 amino acid residues occurred in identical positions. The locations of the four cysteine residues were found to be invariable. A crystallographic study of the Desulfovibrio vulgaris rubredoxin is in progress.", "contents": "Non-heme iron proteins. The amino acid sequence of rubredoxin from Desulfovibrio vulgaris. A non-heme iron protein, rubredoxin has been isolated from the sulfate-reducing bacterium, Desulfovibrio vulgaris, strain Hildenborough. The complete amino acid sequence has been established. The 52 amino acid residues of the protein were aligned with the aid of tryptic and chymotryptic peptides and of a fragment produced by cleavage of the Asn-Gly bond (22-23) by hydroxylamine. The sequence of the first 30 residues of the molecule was determined using an automatic sequenator, after removal of the N-terminal methionine by CNBr. In comparing this sequence with those of Micrococcus aerogenes, Clostridium pasteurianum and Peptostreptococcus elsdenii rubredoxins, a high degree of mutation was observed between these homologous proteins. It has been shown that 20 amino acid residues occurred in identical positions. The locations of the four cysteine residues were found to be invariable. A crystallographic study of the Desulfovibrio vulgaris rubredoxin is in progress."}
{"id": "PMID:7309", "title": "The dissociation of human deoxyhemoglobin and mixed state hemoglobin into monomer.", "content": "The experimental hybridizations between fully deoxygenated human and canine hemoglobins and between half-ligated human hemoglobin and canine cyanomethemoglobin show that new two hybrids in addition to the parent hemoglobins were clearly formed in the mixtures at the high concentration of KI. Thus, human deoxyhemoglobin under the present conditions is in an equilibrium with three species, tetramer in equilibrium dimer in equilibrium monomer. This means that the deoxyhemoglobin is in R-T equilibrium, and shifts considerably toward the R state under the present conditions. On the other hand, the half-ligated hemoglobin in 1.5 M KI becomes much more dissociable than the deoxy T state and appears to be completely transformed into the R state. Nevertheless, the co-operativity, n, is still high (n = 2.0).", "contents": "The dissociation of human deoxyhemoglobin and mixed state hemoglobin into monomer. The experimental hybridizations between fully deoxygenated human and canine hemoglobins and between half-ligated human hemoglobin and canine cyanomethemoglobin show that new two hybrids in addition to the parent hemoglobins were clearly formed in the mixtures at the high concentration of KI. Thus, human deoxyhemoglobin under the present conditions is in an equilibrium with three species, tetramer in equilibrium dimer in equilibrium monomer. This means that the deoxyhemoglobin is in R-T equilibrium, and shifts considerably toward the R state under the present conditions. On the other hand, the half-ligated hemoglobin in 1.5 M KI becomes much more dissociable than the deoxy T state and appears to be completely transformed into the R state. Nevertheless, the co-operativity, n, is still high (n = 2.0)."}
{"id": "PMID:7310", "title": "The interaction of riboflavin with a protein isolated from hen's egg white: a spectrofluorimetric study.", "content": "The interaction of riboflavin with a protein isolated from egg white has been studied spectrofluorimetrically at different pH values. In 0.1 M phosphate buffer pH 7.0; 1:1 complex formation occurs with the association constant Ka = 7.7-10(7) M-1. In the presence of 0.033% sodium dodecyl sulphate, the complex dissociated with a rate constant of 4-10(-2) sec-1 at 29 degrees C. The binding was sensitive to pH and to the antibodies produced against the protein. On lowering the pH from 7 to 4 the binding affinity decreased approximately 100-fold and below pH 4, the binding could not be detected at all. These data, together with those obtained by measuring the fluorescence intensities of riboflavin in presence of N-bromosuccinimide oxidized- and disulphide reduced apoprotein, suggest that carboxyl functions, 1-2 tryptophan residues and 2-3 disulphide bridges are essential for binding. The emission spectra of the protein under different conditions upon excitation at 280 and 295 nm were analyzed to calculate the quantum yield (Q) and the efficiency of energy transfer (e) from tyrosine to tryptophan residues. From these data it was concluded that the energy transfer did not occur with equal efficiency under all conditions and that the tryptophan residues responsible for the riboflavin binding are more accessible to N-bromosuccinimide oxidation than others.", "contents": "The interaction of riboflavin with a protein isolated from hen's egg white: a spectrofluorimetric study. The interaction of riboflavin with a protein isolated from egg white has been studied spectrofluorimetrically at different pH values. In 0.1 M phosphate buffer pH 7.0; 1:1 complex formation occurs with the association constant Ka = 7.7-10(7) M-1. In the presence of 0.033% sodium dodecyl sulphate, the complex dissociated with a rate constant of 4-10(-2) sec-1 at 29 degrees C. The binding was sensitive to pH and to the antibodies produced against the protein. On lowering the pH from 7 to 4 the binding affinity decreased approximately 100-fold and below pH 4, the binding could not be detected at all. These data, together with those obtained by measuring the fluorescence intensities of riboflavin in presence of N-bromosuccinimide oxidized- and disulphide reduced apoprotein, suggest that carboxyl functions, 1-2 tryptophan residues and 2-3 disulphide bridges are essential for binding. The emission spectra of the protein under different conditions upon excitation at 280 and 295 nm were analyzed to calculate the quantum yield (Q) and the efficiency of energy transfer (e) from tyrosine to tryptophan residues. From these data it was concluded that the energy transfer did not occur with equal efficiency under all conditions and that the tryptophan residues responsible for the riboflavin binding are more accessible to N-bromosuccinimide oxidation than others."}
{"id": "PMID:7311", "title": "Histamine (H2) receptor-adenylate cyclase system in pig skin (epidermis).", "content": "Histamine activated adenylate cyclase in pig skin (epidermal) slices, resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of cyclic AMP-phosphodiesterase inhibitors (theophylline, papaverine). A specific H2 receptor inhibitor (metiamide) inhibited the effect of histamine completely, while other antihistamines (diphenhydramine, acetophenazine, perphenazine, fluphenazine, promethazine) inhibited the effect of histamine to various lesser degrees. It has been shown that both epinephrine and prostaglandin E stimulate epidermal adenylate cyclase. Our data using specific blocking agents indicate that histamine, epinephrine and prostaglandin E2 act independently on the epidermal adenylate cyclase system.", "contents": "Histamine (H2) receptor-adenylate cyclase system in pig skin (epidermis). Histamine activated adenylate cyclase in pig skin (epidermal) slices, resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of cyclic AMP-phosphodiesterase inhibitors (theophylline, papaverine). A specific H2 receptor inhibitor (metiamide) inhibited the effect of histamine completely, while other antihistamines (diphenhydramine, acetophenazine, perphenazine, fluphenazine, promethazine) inhibited the effect of histamine to various lesser degrees. It has been shown that both epinephrine and prostaglandin E stimulate epidermal adenylate cyclase. Our data using specific blocking agents indicate that histamine, epinephrine and prostaglandin E2 act independently on the epidermal adenylate cyclase system."}
{"id": "PMID:7312", "title": "Ammonia production by the small intestine of the rat.", "content": "1. Slices of duodenum and jejunum produce ammonia from glutamine in vitro. 2. Ammoniagenesis does not increase in response to acidosis or potassium deficiency, two conditions known to cause enhanced ammoniagenesis in the kidney. 3. Gut contains glutaminase 1 as well as gamma-glutamyl transpeptidase. 4. These enzymes do not show any increase during starvation.", "contents": "Ammonia production by the small intestine of the rat. 1. Slices of duodenum and jejunum produce ammonia from glutamine in vitro. 2. Ammoniagenesis does not increase in response to acidosis or potassium deficiency, two conditions known to cause enhanced ammoniagenesis in the kidney. 3. Gut contains glutaminase 1 as well as gamma-glutamyl transpeptidase. 4. These enzymes do not show any increase during starvation."}
{"id": "PMID:7313", "title": "pH dependence of 13C-15N coupling constants of highly 14N-enriched amino acids isolated from mass cultivation of algae.", "content": "The alga Ankistrodesmus braunii was grown with [14N]nitrate under optimized conditions of a large-scale mass cultivation. 19.7% of the dried algae were isolated as a mixture of amino acids. The 15N-labelled amino acids (15N content up to 98%) were separated by ion exchange chromatography using pyridine acetate gradients. The 15N cotent of the analytically pure amino acid was determined by combined gas-liquid chromatography-mass spectrometry of the trifluoroacetylated methylesters and by emission spectroscopy in the 15N analysator. Using pulse Fourier transform 13C nuclear magnetic resonance, the pH dependence of the 13C-15N coupling constants of Asp, Pro, Ser, Glu, Gly, Ala, Val, Ile and Leu was determined in aqueous solutions. Increasing coupling constants were found with pH and decreasing electron density, respectively. The relation of Binsch et al. (Binsch, G., Lambert, J.B., Roberts, B.W. and Roberts, J.D. (1964) J.Am. Chem. Soc. 86,5564-5570) between the coupling constant and the product of the S-part of the 13C and 15N hybridization SC - SN = 80 - J (13C-45X) fits best in acidic medium. The magnitude of coupling constants correlates well with the electron densities calculated by Del Re et al. (Del Re, G., Pullman, B. and Yonezawa, T. (1963) Biochim. Biophys. Acta 75, 153-182). The recording of 13C nuclear magnetic resonance spectra over the entire pH range revealed no change in the sign of the 13C-15N coupling constants of the amino acids.", "contents": "pH dependence of 13C-15N coupling constants of highly 14N-enriched amino acids isolated from mass cultivation of algae. The alga Ankistrodesmus braunii was grown with [14N]nitrate under optimized conditions of a large-scale mass cultivation. 19.7% of the dried algae were isolated as a mixture of amino acids. The 15N-labelled amino acids (15N content up to 98%) were separated by ion exchange chromatography using pyridine acetate gradients. The 15N cotent of the analytically pure amino acid was determined by combined gas-liquid chromatography-mass spectrometry of the trifluoroacetylated methylesters and by emission spectroscopy in the 15N analysator. Using pulse Fourier transform 13C nuclear magnetic resonance, the pH dependence of the 13C-15N coupling constants of Asp, Pro, Ser, Glu, Gly, Ala, Val, Ile and Leu was determined in aqueous solutions. Increasing coupling constants were found with pH and decreasing electron density, respectively. The relation of Binsch et al. (Binsch, G., Lambert, J.B., Roberts, B.W. and Roberts, J.D. (1964) J.Am. Chem. Soc. 86,5564-5570) between the coupling constant and the product of the S-part of the 13C and 15N hybridization SC - SN = 80 - J (13C-45X) fits best in acidic medium. The magnitude of coupling constants correlates well with the electron densities calculated by Del Re et al. (Del Re, G., Pullman, B. and Yonezawa, T. (1963) Biochim. Biophys. Acta 75, 153-182). The recording of 13C nuclear magnetic resonance spectra over the entire pH range revealed no change in the sign of the 13C-15N coupling constants of the amino acids."}
{"id": "PMID:7314", "title": "Secondary kinase reactions catalyzed by yeast pyruvate kinase.", "content": "1. Yeast pyruvate kinase (EC 2.7.1.40) catalyzes, in addition to the primary, physiologically important reaction, three secondary kinase reactions, the ATP-dependent phosphorylations of fluoride (fluorokinase), hydroxylamine (hydroxylamine kinase) and glycolate (glycolate kinase). 2. These reactions are accelerated by fructose-1,6-bisphosphate, the allosteric activator of the primary reaction. Wth Mg2+ as the required divalent cation, none of these reactions are observed in the absence of fructose-biphosphate. With Mn2+, fructose-bisphosphate is required for the glycolate kinase reaction, but merely stimulates the other reactions. 3. The effect of other divalent cations and pH on three secondary kinase reactions was also examined. 4. Results are compared with those obtained from muscle pyruvate kinase and the implications of the results for the mechanism of the yeast enzyme are discussed.", "contents": "Secondary kinase reactions catalyzed by yeast pyruvate kinase. 1. Yeast pyruvate kinase (EC 2.7.1.40) catalyzes, in addition to the primary, physiologically important reaction, three secondary kinase reactions, the ATP-dependent phosphorylations of fluoride (fluorokinase), hydroxylamine (hydroxylamine kinase) and glycolate (glycolate kinase). 2. These reactions are accelerated by fructose-1,6-bisphosphate, the allosteric activator of the primary reaction. Wth Mg2+ as the required divalent cation, none of these reactions are observed in the absence of fructose-biphosphate. With Mn2+, fructose-bisphosphate is required for the glycolate kinase reaction, but merely stimulates the other reactions. 3. The effect of other divalent cations and pH on three secondary kinase reactions was also examined. 4. Results are compared with those obtained from muscle pyruvate kinase and the implications of the results for the mechanism of the yeast enzyme are discussed."}
{"id": "PMID:7315", "title": "The proton transfer reactions catalyzed by yeast pyruvate kinase.", "content": "1. The proton-transfer reactions of yeast pyruvate kinase (EC 2.7.1.40) were studied. Proton-transfer from C-3 of phosphoenolpyruvate to water occurs only in the presence of the phosphoryl-acceptor ADP. Proton transfer from C-3 of pyruvate to water occurs only in the presence of ATP. However, the proton transfer in the latter case occurs 10-100 times faster than phosphoryl transfer; this supports a mechanism in which proton transfer precedes phosphoryl transfer in the reverse reaction of pyruvate kinase. 2. The characteristics of proton-transfer reactions of yeast pyruvate kinase were compared with those previously reported for rabbit muscle pyruvate kinase (Robinson, JL. and Rose, I.A. (1972) J. Biol. Chem. 247, 1096-1105). The pH-profiles and the divalent cation dependencies were similar for Fru-1,6-P2-activated yeast pyruvate kinase and the muscle enzyme. Pyruvate enolization by yeast pyruvate kinase has an absolute requirement for ATP in contrast to enolization by the muscle enzyme which proceeds when ATP is replaced by Pi or other dianions. 3. Fructose-1,6-bisphosphate was shown to affect the catelytic steps of yeast pyruvate kinase in addition to the binding of substrates. Its role depends on the divalent cation used to activate the enzyme.", "contents": "The proton transfer reactions catalyzed by yeast pyruvate kinase. 1. The proton-transfer reactions of yeast pyruvate kinase (EC 2.7.1.40) were studied. Proton-transfer from C-3 of phosphoenolpyruvate to water occurs only in the presence of the phosphoryl-acceptor ADP. Proton transfer from C-3 of pyruvate to water occurs only in the presence of ATP. However, the proton transfer in the latter case occurs 10-100 times faster than phosphoryl transfer; this supports a mechanism in which proton transfer precedes phosphoryl transfer in the reverse reaction of pyruvate kinase. 2. The characteristics of proton-transfer reactions of yeast pyruvate kinase were compared with those previously reported for rabbit muscle pyruvate kinase (Robinson, JL. and Rose, I.A. (1972) J. Biol. Chem. 247, 1096-1105). The pH-profiles and the divalent cation dependencies were similar for Fru-1,6-P2-activated yeast pyruvate kinase and the muscle enzyme. Pyruvate enolization by yeast pyruvate kinase has an absolute requirement for ATP in contrast to enolization by the muscle enzyme which proceeds when ATP is replaced by Pi or other dianions. 3. Fructose-1,6-bisphosphate was shown to affect the catelytic steps of yeast pyruvate kinase in addition to the binding of substrates. Its role depends on the divalent cation used to activate the enzyme."}
{"id": "PMID:7316", "title": "Importance of SH groups in catalysis by bovine brain acid phosphatase.", "content": "The rate of inactivation of acid phosphatase (EC 3.1.3.2) from bovine brain by dithiobis-(2-nitrobenzoic acid) (Nbs2) is identical to the rate of titration of one of the two SH groups of this enzyme. The rate of inactivation of the enzyme by Nbs2 is pH dependent and, at 300 mM NaCl, can be described by the reaction of a single SH group of pK 8.4. At low ionic strength the pK determined from the k inactivation vs. pH profile is 7.7 and the results deviate markedly from the predicted values at pH values less than or equal to 6. The decrease of V upon addition of salts is paralleled by the decrease of inactivation rate by Nbs2. The relevance of SH groups in catalysis by bovine brain acid phosphatase is discussed in terms of these data.", "contents": "Importance of SH groups in catalysis by bovine brain acid phosphatase. The rate of inactivation of acid phosphatase (EC 3.1.3.2) from bovine brain by dithiobis-(2-nitrobenzoic acid) (Nbs2) is identical to the rate of titration of one of the two SH groups of this enzyme. The rate of inactivation of the enzyme by Nbs2 is pH dependent and, at 300 mM NaCl, can be described by the reaction of a single SH group of pK 8.4. At low ionic strength the pK determined from the k inactivation vs. pH profile is 7.7 and the results deviate markedly from the predicted values at pH values less than or equal to 6. The decrease of V upon addition of salts is paralleled by the decrease of inactivation rate by Nbs2. The relevance of SH groups in catalysis by bovine brain acid phosphatase is discussed in terms of these data."}
{"id": "PMID:7317", "title": "Guanylate cyclase. Existence of different forms and their regulation by nucleotides in calf uterus.", "content": "The activity of calf uterus guanylate cyclase (EC 4.6.1.2) exists in at least two and most probably three distinct forms. The cytosolic enzyme exhibits hyperbolic substrate curves with respect to GTP and Mn2+, while the particulate cyclases (nuclear and microsomal)display sigmoidal (GTP) and hyperbolic (Mn2+) relationships. The Hill coefficient for the GTP dependence is 0.9 for the cytosolic, 1.5 for the nuclear, and 1.4 for the microsomal enzyme. The cytosolic enzyme has a Km for GTP of 70 muM while half maximal velocity occurs at 90 and 100 muM GTP for the nuclear and microsomal enzymes, respectively. The Ka for Mn2+ is 0.57, 0.71 or 0.75 mM for the cytosolic, nuclear, or microsomal enzyme, respectively.", "contents": "Guanylate cyclase. Existence of different forms and their regulation by nucleotides in calf uterus. The activity of calf uterus guanylate cyclase (EC 4.6.1.2) exists in at least two and most probably three distinct forms. The cytosolic enzyme exhibits hyperbolic substrate curves with respect to GTP and Mn2+, while the particulate cyclases (nuclear and microsomal)display sigmoidal (GTP) and hyperbolic (Mn2+) relationships. The Hill coefficient for the GTP dependence is 0.9 for the cytosolic, 1.5 for the nuclear, and 1.4 for the microsomal enzyme. The cytosolic enzyme has a Km for GTP of 70 muM while half maximal velocity occurs at 90 and 100 muM GTP for the nuclear and microsomal enzymes, respectively. The Ka for Mn2+ is 0.57, 0.71 or 0.75 mM for the cytosolic, nuclear, or microsomal enzyme, respectively."}
{"id": "PMID:7318", "title": "Properties of highly purified lysyl oxidase from embryonic chick cartilage.", "content": "Lysyl oxidase the enzyme which oxidately deaminates lysine residues in collagen and elastin, was purified from embryonic chick cartialge by employing an affinity column of lathyritic rat skin collagen coupled to Sepharose, followed by separation on DEAE-cellulose. An enzyme preparation was obtained which was pure as shown by polyacrylamide gel electrophoresis. The specific activity was 1800-fold higher than that of the original extract. The pure enzyme utilized both collagen and elastin substrate. Furthermore, the ratios of enzyme activity with elastin substrate versus that with collagen substrate were the same at all stages of purity. Only one protein band was found after polyacrylamide gel electrophoresis of the pure lysyl oxidase in sodium dodecyl sulfate and mercaptoethanol. The molecular weight was estimated to be 28000. It was found that the enzyme contained a large number of cysteine and tyrosine residues. Evidence was obtained for molecular heterogeneity of lysyl oxidase. The enzyme eluted from DEAE-cellulsoe in at least four distinct regions. When the peaks were rechromatographed separately, they eluted at salt concentrations similar to those of the original chromatogram. However, the substrate specificity and the electrophoretic mobility on polyacrylamide gel were the same for all enzyme fractions.", "contents": "Properties of highly purified lysyl oxidase from embryonic chick cartilage. Lysyl oxidase the enzyme which oxidately deaminates lysine residues in collagen and elastin, was purified from embryonic chick cartialge by employing an affinity column of lathyritic rat skin collagen coupled to Sepharose, followed by separation on DEAE-cellulose. An enzyme preparation was obtained which was pure as shown by polyacrylamide gel electrophoresis. The specific activity was 1800-fold higher than that of the original extract. The pure enzyme utilized both collagen and elastin substrate. Furthermore, the ratios of enzyme activity with elastin substrate versus that with collagen substrate were the same at all stages of purity. Only one protein band was found after polyacrylamide gel electrophoresis of the pure lysyl oxidase in sodium dodecyl sulfate and mercaptoethanol. The molecular weight was estimated to be 28000. It was found that the enzyme contained a large number of cysteine and tyrosine residues. Evidence was obtained for molecular heterogeneity of lysyl oxidase. The enzyme eluted from DEAE-cellulsoe in at least four distinct regions. When the peaks were rechromatographed separately, they eluted at salt concentrations similar to those of the original chromatogram. However, the substrate specificity and the electrophoretic mobility on polyacrylamide gel were the same for all enzyme fractions."}
{"id": "PMID:7319", "title": "Oxidation of sarcosine and N-alkyl derivatives of glycine by D-amino-acid oxidase.", "content": "1. Sarcosine was oxidized by D-amino-acid oxidase (D-amino-acid: O2 oxidoreductase (deaminating), EC 1.4.3.3) to yield methylamine and glyoxylic acid. A seriies of N-alkyl glycines were also oxidized by this enzyme. 2. N-Acetyl- and N-Phenylglycine inhibited the oxidase by competing with the substrate, while N-methyl-N-acetylglycine did not bind to the enzyme. This suggests the requirement of at least one unsubstituted hydrogen atom at the amino group ofglycine for binding. 3. The primary step in the reaction was the release of a proton from the substrate, indicating the formation of a substituted imino acid, which was spontaneously hydrolyzed to glyoxylic acid acid and an amine.", "contents": "Oxidation of sarcosine and N-alkyl derivatives of glycine by D-amino-acid oxidase. 1. Sarcosine was oxidized by D-amino-acid oxidase (D-amino-acid: O2 oxidoreductase (deaminating), EC 1.4.3.3) to yield methylamine and glyoxylic acid. A seriies of N-alkyl glycines were also oxidized by this enzyme. 2. N-Acetyl- and N-Phenylglycine inhibited the oxidase by competing with the substrate, while N-methyl-N-acetylglycine did not bind to the enzyme. This suggests the requirement of at least one unsubstituted hydrogen atom at the amino group ofglycine for binding. 3. The primary step in the reaction was the release of a proton from the substrate, indicating the formation of a substituted imino acid, which was spontaneously hydrolyzed to glyoxylic acid acid and an amine."}
{"id": "PMID:7320", "title": "Factors affecting the ADP/O ratio in isolated chloroplasts.", "content": "(1) The effect of gradual disruption of the outer membrane of intact chloroplasts on CO2 fixation, electron transport and phosphorylation was investigated. The results suggested that whilst ferricyanide and substrate amounts of ADP enter intact chloroplasts only very slowly, methyl viologen rapidly penetrates the outer membrane. (2) Preparatwons of intact pea chloroplasts had an ATP-consuming reaction which resulted in decreased ADP/O ratios when noncyclic electron transport was measured after disruption of the outer membrane. The ATP-consuming reaction was removed into the supernatant after washing the disrupted chloroplasts. The resulting washed chloroplasts gave ADP/O ratios of 1.5-1.6 for ferricyanide and 1.9-2.0 for methyl viologen. (3) Preparations of intact spinach chloroplasts had lower activity of the ATP-consuming reaction and gave similar ADP/O ratios to washed pea chloroplasts. The ADP/O ratios of spinach chloroplasts did not alter significantly after washing. (4) An investigation of the effect of various assay conditions on the ADP/O ratio showed that the phosphate concentration was critical in obtaining optimal values for ADP/O ratio. Decreasing the phosphate concentration below 10 mM decreased the ADP/O ratio significantly. (5) It is suggested that the maximum ADP/O ratio of chloroplasts is 2.0 but that lower values can be obtained in the presence of an ATP-consuming reaction, under suboptimal assay conditions or where the chloroplasts are structurally damaged.", "contents": "Factors affecting the ADP/O ratio in isolated chloroplasts. (1) The effect of gradual disruption of the outer membrane of intact chloroplasts on CO2 fixation, electron transport and phosphorylation was investigated. The results suggested that whilst ferricyanide and substrate amounts of ADP enter intact chloroplasts only very slowly, methyl viologen rapidly penetrates the outer membrane. (2) Preparatwons of intact pea chloroplasts had an ATP-consuming reaction which resulted in decreased ADP/O ratios when noncyclic electron transport was measured after disruption of the outer membrane. The ATP-consuming reaction was removed into the supernatant after washing the disrupted chloroplasts. The resulting washed chloroplasts gave ADP/O ratios of 1.5-1.6 for ferricyanide and 1.9-2.0 for methyl viologen. (3) Preparations of intact spinach chloroplasts had lower activity of the ATP-consuming reaction and gave similar ADP/O ratios to washed pea chloroplasts. The ADP/O ratios of spinach chloroplasts did not alter significantly after washing. (4) An investigation of the effect of various assay conditions on the ADP/O ratio showed that the phosphate concentration was critical in obtaining optimal values for ADP/O ratio. Decreasing the phosphate concentration below 10 mM decreased the ADP/O ratio significantly. (5) It is suggested that the maximum ADP/O ratio of chloroplasts is 2.0 but that lower values can be obtained in the presence of an ATP-consuming reaction, under suboptimal assay conditions or where the chloroplasts are structurally damaged."}
{"id": "PMID:7321", "title": "Photosynthesis in a reconstituted chloroplast system from spinach. Some factors affecting CO2-dependent oxygen evolution with fructose-1,6-bisphosphate as substrate.", "content": "When envelope-free spinach chloroplasts are incubated with stromal protein, catalytic NADP, catalytic ADP, radioactive bicarbonate and fructose 1,6-bisphosphate, 14CO2 fixation starts immediately upon illumination but oxygen evolution is delayed. The delay is increased by the addition of fructose 6-phosphate and by a variety of factors known (or believed) to increase fructose bisphosphatase activity (such as dithiothreitol, more alkaline pH, higher [Mg] and antimycin A). Conversely, the lag can be decreased or eliminated by the addition of an ATP-generating system. Bearing in mind the known inhibition, by ADP, of sn-phospho-3-glycerate (3-phosphoglycerate) reduction it is concluded that the lag in O2 evolution results from the production of ribulose 5-phosphate from fructose bisphosphate and that this in turn inhibits the reoxidation of NADPH by adversely affecting the ADP/ATP ratio. The results are discussed in their relation to the mode of action of antimycin A and to regulation of the reductive pentose phosphate pathway.", "contents": "Photosynthesis in a reconstituted chloroplast system from spinach. Some factors affecting CO2-dependent oxygen evolution with fructose-1,6-bisphosphate as substrate. When envelope-free spinach chloroplasts are incubated with stromal protein, catalytic NADP, catalytic ADP, radioactive bicarbonate and fructose 1,6-bisphosphate, 14CO2 fixation starts immediately upon illumination but oxygen evolution is delayed. The delay is increased by the addition of fructose 6-phosphate and by a variety of factors known (or believed) to increase fructose bisphosphatase activity (such as dithiothreitol, more alkaline pH, higher [Mg] and antimycin A). Conversely, the lag can be decreased or eliminated by the addition of an ATP-generating system. Bearing in mind the known inhibition, by ADP, of sn-phospho-3-glycerate (3-phosphoglycerate) reduction it is concluded that the lag in O2 evolution results from the production of ribulose 5-phosphate from fructose bisphosphate and that this in turn inhibits the reoxidation of NADPH by adversely affecting the ADP/ATP ratio. The results are discussed in their relation to the mode of action of antimycin A and to regulation of the reductive pentose phosphate pathway."}
{"id": "PMID:7322", "title": "Light-driven proton translocations in Halobacterium halobium.", "content": "The purple membrane of Halobacterium halobium acts as a light-driven proton pump, ejecting protons from the cell interior into the medium and generating electrochemical proton gradient across the cell membrane. However, the type response of cells to light as measured with a pH electrode in the medium consists of an initial net inflow of protons which subsides and is then replaced by a net outflow which exponentially approaches a new lower steady state pH level. When the light turned off a small transient acidification occurs before the pH returns to the original dark level. We present experiments suggesting that the initial inflow of protons is triggered by the beginning ejection of protons through the purple membrane and that the initial inflow rate is larger than the continuing light-driven outflow. When the initial inflow has decreased exponentially to a small value, the outflow dominates and causes the net acidification of the medium. The initial inflow is apparently driven by a pre-existing electrochemical gradient across the membrane, which the cells can maintain for extended times in the absence of light and oxygen. Treatments which collapse this gradient such as addition of small concentrations of uncouplers abolish the initial inflow. The triggered inflow occurs through the ATPase and is accompanied by ATP synthesis. Inhibitors of the ATPase such as N,N'-dicyclohexylcarbodiimide (DCCD) inhibit ATP synthesis and abolish the inflow. They also abolish the transient light-off acidification, which is apparently caused by a short burst of ATP hydrolysis before the enzyme is blocked by its endogenous inhibitor. Similar transient inflows and outflows of protons are also observed when anaerobic cells are exposed to short oxygen pulses.", "contents": "Light-driven proton translocations in Halobacterium halobium. The purple membrane of Halobacterium halobium acts as a light-driven proton pump, ejecting protons from the cell interior into the medium and generating electrochemical proton gradient across the cell membrane. However, the type response of cells to light as measured with a pH electrode in the medium consists of an initial net inflow of protons which subsides and is then replaced by a net outflow which exponentially approaches a new lower steady state pH level. When the light turned off a small transient acidification occurs before the pH returns to the original dark level. We present experiments suggesting that the initial inflow of protons is triggered by the beginning ejection of protons through the purple membrane and that the initial inflow rate is larger than the continuing light-driven outflow. When the initial inflow has decreased exponentially to a small value, the outflow dominates and causes the net acidification of the medium. The initial inflow is apparently driven by a pre-existing electrochemical gradient across the membrane, which the cells can maintain for extended times in the absence of light and oxygen. Treatments which collapse this gradient such as addition of small concentrations of uncouplers abolish the initial inflow. The triggered inflow occurs through the ATPase and is accompanied by ATP synthesis. Inhibitors of the ATPase such as N,N'-dicyclohexylcarbodiimide (DCCD) inhibit ATP synthesis and abolish the inflow. They also abolish the transient light-off acidification, which is apparently caused by a short burst of ATP hydrolysis before the enzyme is blocked by its endogenous inhibitor. Similar transient inflows and outflows of protons are also observed when anaerobic cells are exposed to short oxygen pulses."}
{"id": "PMID:7323", "title": "Primary reactions of photosystem II at low pH. 2. Light-induced changes of absorbance and electron spin resonance in spinach chloroplasts.", "content": "The effects of lowering the pH on Photosystem II has been studied by measuring changes in absorbance and electron spin resonance in spinach chloroplasts. At pH values around 4 a light-induced dark-reversible chlorophyll oxidation by Photosystem II was observed. This chlorophyll is presumably the primary electron donor of system II. At pH values between 5 and 4 steady state illumination induced an ESR signal, similar in shape and amplitude to signal II, which was rapidly reversed in the dark. This may reflect the accumulation of the oxidized secondary donor upon inhibition of oxygen evolution. Near pH 4 the rapidly reversible signal and the stable and slowly decaying components of signal II disappeared irreversibly concomitant with the release of bound manganese. The results are discussed in relation to the effects of low pH on prompt and delayed fluorescence reported earlier (van Gorkom, H.J., Pulles, M.P.J., Haveman, J. and den Haan, G.A. (1976) Biochim. Biophys, Acta 423, 217-226).", "contents": "Primary reactions of photosystem II at low pH. 2. Light-induced changes of absorbance and electron spin resonance in spinach chloroplasts. The effects of lowering the pH on Photosystem II has been studied by measuring changes in absorbance and electron spin resonance in spinach chloroplasts. At pH values around 4 a light-induced dark-reversible chlorophyll oxidation by Photosystem II was observed. This chlorophyll is presumably the primary electron donor of system II. At pH values between 5 and 4 steady state illumination induced an ESR signal, similar in shape and amplitude to signal II, which was rapidly reversed in the dark. This may reflect the accumulation of the oxidized secondary donor upon inhibition of oxygen evolution. Near pH 4 the rapidly reversible signal and the stable and slowly decaying components of signal II disappeared irreversibly concomitant with the release of bound manganese. The results are discussed in relation to the effects of low pH on prompt and delayed fluorescence reported earlier (van Gorkom, H.J., Pulles, M.P.J., Haveman, J. and den Haan, G.A. (1976) Biochim. Biophys, Acta 423, 217-226)."}
{"id": "PMID:7324", "title": "Ca++ binding properties of human prothrombin.", "content": "The binding of Ca++ to human prothrombin has been investigated by equilibrium dialysis. The protein exhibited a positive cooperativity phenomenon for the first three Ca++ bound. Eleven to twelve Ca++ binding sites have been found. They could be differentiated in terms of two classes of sites with respect to their Ca++ affinity: 5 strong binding sites (log Kassoc = 3.9) and 7 weak binding sites (log Kassoc = 2.9). We attempted to determine the Hill coefficient of the strong binding sites responsible for cooperativity. Results have been compared to data previously reported for bovine prothrombin.", "contents": "Ca++ binding properties of human prothrombin. The binding of Ca++ to human prothrombin has been investigated by equilibrium dialysis. The protein exhibited a positive cooperativity phenomenon for the first three Ca++ bound. Eleven to twelve Ca++ binding sites have been found. They could be differentiated in terms of two classes of sites with respect to their Ca++ affinity: 5 strong binding sites (log Kassoc = 3.9) and 7 weak binding sites (log Kassoc = 2.9). We attempted to determine the Hill coefficient of the strong binding sites responsible for cooperativity. Results have been compared to data previously reported for bovine prothrombin."}
{"id": "PMID:7325", "title": "Structure-volume relationships in hemoglobin. A densitometric and dilatometric study of the oxy leads to deoxy transformation.", "content": "Partial volume measurements have been performed for human hemoglobin, both on the oxygenated and deoxygenated forms. Density measurements (by pycnometry) give vHbO2 = 0.752 +/- 0.002 and vHb =0.753 +/- 0.006 for the partial specific volume and do not distinguish between the two different structures. Differential measurements, by dilatometry, however, show a signigicantly higher molal volume (of about 50 cm3/mol hemoglobin tetramer) for the deoxy over the oxygenated from at pH 7. The same reaction, at pH 9, gives a much smaller increase or even a decrease of volume. The different volume changes at pH 7 and at pH 9 are not due to the so-called Bohr ionization but to the weakening, at pH 9 compared to pH 7, of stabilising salt linkages in the deoxy structure.", "contents": "Structure-volume relationships in hemoglobin. A densitometric and dilatometric study of the oxy leads to deoxy transformation. Partial volume measurements have been performed for human hemoglobin, both on the oxygenated and deoxygenated forms. Density measurements (by pycnometry) give vHbO2 = 0.752 +/- 0.002 and vHb =0.753 +/- 0.006 for the partial specific volume and do not distinguish between the two different structures. Differential measurements, by dilatometry, however, show a signigicantly higher molal volume (of about 50 cm3/mol hemoglobin tetramer) for the deoxy over the oxygenated from at pH 7. The same reaction, at pH 9, gives a much smaller increase or even a decrease of volume. The different volume changes at pH 7 and at pH 9 are not due to the so-called Bohr ionization but to the weakening, at pH 9 compared to pH 7, of stabilising salt linkages in the deoxy structure."}
{"id": "PMID:7326", "title": "Thermodynamics of hexokinase catalyzed reactions. II. Measurement and calculation of enthalpies of reaction as a function of magnesium ion concentration.", "content": "Enthalpies of phosphorylation of glucose by adenosine 5'-triphosphate have been measured as a function of concentrations of magnesium chloride in TRIS/TRIS-HCl buffer in the pH range 8.64 to 8.98. These measurements are compared with the results of calculations of these enthalpies that use a coupled equilibrium formalism with equilibrium data and enthalpy values selected from the literature. The experimental results span the range of magnesium ion concentrations 1 X 10(-6) to 0.3 mol alpha-1 and show a total variation in the enthalpy of reaction of almost 10 kJ mol-1, with the most exothermic reaction occurring at a magnesium ion concentration of 6.0 X 10(-4) mol alpha-1. The calculated enthalpies of reaction, except for the magnesium ion concentration range 4 X 10(-6) to 5 X 10(-4) mol alpha-1, are, within estimated uncertainty intervals (0.8 to 10.2 kJ mol-1), in agreement with the measured values.", "contents": "Thermodynamics of hexokinase catalyzed reactions. II. Measurement and calculation of enthalpies of reaction as a function of magnesium ion concentration. Enthalpies of phosphorylation of glucose by adenosine 5'-triphosphate have been measured as a function of concentrations of magnesium chloride in TRIS/TRIS-HCl buffer in the pH range 8.64 to 8.98. These measurements are compared with the results of calculations of these enthalpies that use a coupled equilibrium formalism with equilibrium data and enthalpy values selected from the literature. The experimental results span the range of magnesium ion concentrations 1 X 10(-6) to 0.3 mol alpha-1 and show a total variation in the enthalpy of reaction of almost 10 kJ mol-1, with the most exothermic reaction occurring at a magnesium ion concentration of 6.0 X 10(-4) mol alpha-1. The calculated enthalpies of reaction, except for the magnesium ion concentration range 4 X 10(-6) to 5 X 10(-4) mol alpha-1, are, within estimated uncertainty intervals (0.8 to 10.2 kJ mol-1), in agreement with the measured values."}
{"id": "PMID:7327", "title": "The influence of organic phosphates on the Bohr effect of human hemoglobin valency hybrids.", "content": "The Bohr effect of hemoglobin and that of the aquomet and cyanomet valency hybrids was measured in the presence and the absence of IHP (inositol hexaphosphate) and DPG (2,3-diphosphoglycerate). In the absence of these organic phosphates the four hybrids show similar, but suppressed Bohr effects as compared to hemoglobin. Addition of IHP and DPG results in all cases in an increase of the Bohr effect. The additional phosphate induced Bohr effect of the hybrids with the alpha chain in the oxidized form is almost identical to that of hemoglobin, while this effect of the hybrids with oxidized beta chains is slighly lower than that of hemoglobin. The results suggest (a) that the Bohr effect is correlated to the ligation state of the hemoglobin molecule rather than to its quaternary structure (b) that the additional phosphate induced Bohr effect is related to the change in quaternary structure of the tetramer, and (c) that with respect to the Bohr effect of the hybrids there is no difference between high and low spin species.", "contents": "The influence of organic phosphates on the Bohr effect of human hemoglobin valency hybrids. The Bohr effect of hemoglobin and that of the aquomet and cyanomet valency hybrids was measured in the presence and the absence of IHP (inositol hexaphosphate) and DPG (2,3-diphosphoglycerate). In the absence of these organic phosphates the four hybrids show similar, but suppressed Bohr effects as compared to hemoglobin. Addition of IHP and DPG results in all cases in an increase of the Bohr effect. The additional phosphate induced Bohr effect of the hybrids with the alpha chain in the oxidized form is almost identical to that of hemoglobin, while this effect of the hybrids with oxidized beta chains is slighly lower than that of hemoglobin. The results suggest (a) that the Bohr effect is correlated to the ligation state of the hemoglobin molecule rather than to its quaternary structure (b) that the additional phosphate induced Bohr effect is related to the change in quaternary structure of the tetramer, and (c) that with respect to the Bohr effect of the hybrids there is no difference between high and low spin species."}
{"id": "PMID:7328", "title": "[Effect of blocking the neuronal and extraneuronal uptake of bioamines on the adrenosensitizing action of tricyclic antidepressants].", "content": "Tests conducted on isolated and denervated preparations of the rat seminal duct brought evidence that tricyclic antidepressants (melipromine, noverile and azaphen) when employed in low concentrations (1-10(-9) g/ml) produced an adrenosensitizing effect. Denervation with the subsequent block by desoxycorticosterone (1-10(-5) g/ml) of exteraneuronal amine uptake did not alter the position, shape and inclination of the \"concentration-effect\" noradrenaline curves received in the presence of noverile and cocaine. It is believed that there exists a predominance of the postsynaptic mechanism of the aminosensitizing action of tricyclic antidepressants on the smooth muscle organ.", "contents": "[Effect of blocking the neuronal and extraneuronal uptake of bioamines on the adrenosensitizing action of tricyclic antidepressants]. Tests conducted on isolated and denervated preparations of the rat seminal duct brought evidence that tricyclic antidepressants (melipromine, noverile and azaphen) when employed in low concentrations (1-10(-9) g/ml) produced an adrenosensitizing effect. Denervation with the subsequent block by desoxycorticosterone (1-10(-5) g/ml) of exteraneuronal amine uptake did not alter the position, shape and inclination of the \"concentration-effect\" noradrenaline curves received in the presence of noverile and cocaine. It is believed that there exists a predominance of the postsynaptic mechanism of the aminosensitizing action of tricyclic antidepressants on the smooth muscle organ."}
{"id": "PMID:7329", "title": "[Capability of lymphocytes, stimulated in vitro with phytohemagglutinins to accomplish the graft versus host reaction].", "content": "Lymph node cells from CBA mice cultivated in the presence of PHA for 2 hours proved to be more potent, and for 44 hours--less potent as compared with normal non-cultivated cells in their capacity to realize the GVHR after injection to sublethally irradiated (CBAXC57BL) F1 recipients. Syngeneic or killed allogeneic lymphocytes cultivated similarly and phytohemagglutinin were found to be deprived of this potency.", "contents": "[Capability of lymphocytes, stimulated in vitro with phytohemagglutinins to accomplish the graft versus host reaction]. Lymph node cells from CBA mice cultivated in the presence of PHA for 2 hours proved to be more potent, and for 44 hours--less potent as compared with normal non-cultivated cells in their capacity to realize the GVHR after injection to sublethally irradiated (CBAXC57BL) F1 recipients. Syngeneic or killed allogeneic lymphocytes cultivated similarly and phytohemagglutinin were found to be deprived of this potency."}
{"id": "PMID:7334", "title": "Selectivity of beta-adrenoceptor agonists and antagonists on bronchial, skeletal, vascular and cardiac muscle in the anaesthetized cat.", "content": "1 The potencies of fifteen beta-adrenoceptor agonists of widely differing chemical structures were compared with that of (-)-isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The beta-adrenoceptor antagonist potencies of propranolol and practolol were determined against (-)-isoprenaline in the same model. 2 (-)-Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003-0.01 mug/kg and maximal or near maximal responses were produced by 0.3-1 mug/kg. Trimetoquinol was also an essentially unselective agonist. 3 For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate. 4 The remaining agonist - AH 7616 (4-hydroxy-alpha1-[[(1-methyl-3,3-diphenyl-propyl)amino]-methyl]-m-xylene-alpha1, alpha3-diol, acetate) - was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5-hydroxytryptamine (5-HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5-HT antagonist action in addition to its beta-adrenoceptor agonist action. 5 The fifteen test agonists were longer acting than (-)-isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The beta-adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10-12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure. 7 These findings suggest that it may not be possible to separate the bronchodilating and tremorenhancing properties of beta-adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual beta-adrenoceptor sub-classification.", "contents": "Selectivity of beta-adrenoceptor agonists and antagonists on bronchial, skeletal, vascular and cardiac muscle in the anaesthetized cat. 1 The potencies of fifteen beta-adrenoceptor agonists of widely differing chemical structures were compared with that of (-)-isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The beta-adrenoceptor antagonist potencies of propranolol and practolol were determined against (-)-isoprenaline in the same model. 2 (-)-Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003-0.01 mug/kg and maximal or near maximal responses were produced by 0.3-1 mug/kg. Trimetoquinol was also an essentially unselective agonist. 3 For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate. 4 The remaining agonist - AH 7616 (4-hydroxy-alpha1-[[(1-methyl-3,3-diphenyl-propyl)amino]-methyl]-m-xylene-alpha1, alpha3-diol, acetate) - was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5-hydroxytryptamine (5-HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5-HT antagonist action in addition to its beta-adrenoceptor agonist action. 5 The fifteen test agonists were longer acting than (-)-isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The beta-adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10-12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure. 7 These findings suggest that it may not be possible to separate the bronchodilating and tremorenhancing properties of beta-adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual beta-adrenoceptor sub-classification."}
{"id": "PMID:7332", "title": "A method of continuous recording on microsamples of the Hb-O2 association curve. I. Technique and direct registration of standard results.", "content": "A modified technique for continuous recording of the Hb-O2 association curve for blood samples is proposed. The following alterations to the classical method of Duvelleroy et al. (5) were studied and validated: 1) dilution of blood micro-samples (200-400 mul) to 10 ml of a buffered phosphate solution; 2) use of a (CO2, O2) mixture allowing the maintenance of standard conditions (pH=7.40, PCO2=40 Torr) during the entire oxygenation process. The advantages of such modifications were: 1) reducing the time necessary for both deoxygenation and drawing Hb-O2 association curve (to about 20 min), hence permitting to work out large series of samples; 2) avoiding the necessity of imprecise a posteriori corrections, thus permitting analysis of the different components of the BOHR effect.", "contents": "A method of continuous recording on microsamples of the Hb-O2 association curve. I. Technique and direct registration of standard results. A modified technique for continuous recording of the Hb-O2 association curve for blood samples is proposed. The following alterations to the classical method of Duvelleroy et al. (5) were studied and validated: 1) dilution of blood micro-samples (200-400 mul) to 10 ml of a buffered phosphate solution; 2) use of a (CO2, O2) mixture allowing the maintenance of standard conditions (pH=7.40, PCO2=40 Torr) during the entire oxygenation process. The advantages of such modifications were: 1) reducing the time necessary for both deoxygenation and drawing Hb-O2 association curve (to about 20 min), hence permitting to work out large series of samples; 2) avoiding the necessity of imprecise a posteriori corrections, thus permitting analysis of the different components of the BOHR effect."}
{"id": "PMID:7335", "title": "Blockade by burimamide of the restorative effect of histamine in tetrodotoxin-treated heart preparations.", "content": "1 In isolated heart preparations in which fast sodium channels were blocked by tetrodotoxin (2-4 x 10(-5) M), excitability was restored by histamine (6 x 10(-6) M to 10(-5) M). 2 This effect was antagonized by EDTA (2 X 10(-6) M),D600 compound (0.5mug/ml) and the H2-receptor antagonist, burimamide(2 X 10(-4) M).", "contents": "Blockade by burimamide of the restorative effect of histamine in tetrodotoxin-treated heart preparations. 1 In isolated heart preparations in which fast sodium channels were blocked by tetrodotoxin (2-4 x 10(-5) M), excitability was restored by histamine (6 x 10(-6) M to 10(-5) M). 2 This effect was antagonized by EDTA (2 X 10(-6) M),D600 compound (0.5mug/ml) and the H2-receptor antagonist, burimamide(2 X 10(-4) M)."}
{"id": "PMID:7336", "title": "Investigations to characterize a new anti-arrhythmic drug, ORG 6001 including a simple test for calcium antagonism.", "content": "1 The compound Org 6001 (3alpha-amino-2beta-hydroxy-5alpha-androstan-17-one hydrochloride) was found in recent experiments to exhibit anti-arrhythmic activity. Evidence is presented in this paper concerning its mode of action. 2 Org 6001 was 1.8 times more potent than procaine as a local anaesthetic on desheathed frog nerve. 3 Org 6001 had no effect on the resting potential of isolated cardiac muscle of rabbit, but greatly reduced the maximum rate of depolarization tion (MRD). The action potential duration TAPD) WAS MARGINALLY PROLONGED IN ATRIAL AND VENTRICULAR MUSCLE. 4 Org 6001 preferentially shortened APD in that part of the Purkinje system in which APD is normally longer than elsewhere, so that APD", "contents": "Investigations to characterize a new anti-arrhythmic drug, ORG 6001 including a simple test for calcium antagonism. 1 The compound Org 6001 (3alpha-amino-2beta-hydroxy-5alpha-androstan-17-one hydrochloride) was found in recent experiments to exhibit anti-arrhythmic activity. Evidence is presented in this paper concerning its mode of action. 2 Org 6001 was 1.8 times more potent than procaine as a local anaesthetic on desheathed frog nerve. 3 Org 6001 had no effect on the resting potential of isolated cardiac muscle of rabbit, but greatly reduced the maximum rate of depolarization tion (MRD). The action potential duration TAPD) WAS MARGINALLY PROLONGED IN ATRIAL AND VENTRICULAR MUSCLE. 4 Org 6001 preferentially shortened APD in that part of the Purkinje system in which APD is normally longer than elsewhere, so that APD"}
{"id": "PMID:7333", "title": "[A method of continuous recording on microsamples of the Hb-O2 association curve. II. A study of Bohr effect and carbamino-formation (author's transl)].", "content": "The authors have worked out an adaptation to microsamples (200-400 mul) of the DUVELLEROY et al. method, allowing the continous registration of the O2-Hb association curve. The microsample being diluted in buffer solution, it is possible to predetermine its pH and PCO2. The prefixed conditions are maintained during the initial deoxygenation phase, and all along the curve registration. Moreover, the adjustment to the desired values of the pH and PCO2 allows the quantification of total BOHR effect, proton BOHR effect and carbamino-formation, during the course of oxygenation.", "contents": "[A method of continuous recording on microsamples of the Hb-O2 association curve. II. A study of Bohr effect and carbamino-formation (author's transl)]. The authors have worked out an adaptation to microsamples (200-400 mul) of the DUVELLEROY et al. method, allowing the continous registration of the O2-Hb association curve. The microsample being diluted in buffer solution, it is possible to predetermine its pH and PCO2. The prefixed conditions are maintained during the initial deoxygenation phase, and all along the curve registration. Moreover, the adjustment to the desired values of the pH and PCO2 allows the quantification of total BOHR effect, proton BOHR effect and carbamino-formation, during the course of oxygenation."}
{"id": "PMID:7337", "title": "The effects of pentobarbitone and pethidine on foetal breathing movements in sheep.", "content": "1 Small doses of pentobarbitone (4 mg/kg i.v.) administered to sheep in the last third of pregancy had little overt effect on the mothers. In the foetus they caused arrest of breathing movements, an alteration in the character of the electrocorticogram and cardiovascular changes which varied with gestational age. 2 In contrast, relatively large doses of pethidine (100-200 mg) admininstered to the mother had no consistent effect on normal foetal breathing movements, though they abolished the foetal response to hypercapnia. 3 The results are discussed in relation to feotal sleep state.", "contents": "The effects of pentobarbitone and pethidine on foetal breathing movements in sheep. 1 Small doses of pentobarbitone (4 mg/kg i.v.) administered to sheep in the last third of pregancy had little overt effect on the mothers. In the foetus they caused arrest of breathing movements, an alteration in the character of the electrocorticogram and cardiovascular changes which varied with gestational age. 2 In contrast, relatively large doses of pethidine (100-200 mg) admininstered to the mother had no consistent effect on normal foetal breathing movements, though they abolished the foetal response to hypercapnia. 3 The results are discussed in relation to feotal sleep state."}
{"id": "PMID:7342", "title": "Comparison of antihypertensive activity of beta-blocking drugs during chronic treatment.", "content": "The hypotensive activity of five beta-adrenoceptor antagonists with different ancillary pharmacological properties was compared in a randomised double-blind factorial trial in 25 untreated patients with stable, uncomplicated essential hypertension. In doses that produced similar reductions in exercise tachycardia all drugs had similar blood-pressure lowering activity, greater on systolic than diastolic pressure and greatest during exercise. With the exception of vasodilator activity the possession of any particular combinaton of ancillary pharmacological properties did not significantly influence the specific antihypertensive activity of these compounds.", "contents": "Comparison of antihypertensive activity of beta-blocking drugs during chronic treatment. The hypotensive activity of five beta-adrenoceptor antagonists with different ancillary pharmacological properties was compared in a randomised double-blind factorial trial in 25 untreated patients with stable, uncomplicated essential hypertension. In doses that produced similar reductions in exercise tachycardia all drugs had similar blood-pressure lowering activity, greater on systolic than diastolic pressure and greatest during exercise. With the exception of vasodilator activity the possession of any particular combinaton of ancillary pharmacological properties did not significantly influence the specific antihypertensive activity of these compounds."}
{"id": "PMID:7347", "title": "Pain as a major cause of postoperative nausea.", "content": "The incidence of nausea in relation to pain was recorded in 104 patients after abdominal operations. Ten per cent of the patients had episodes of nausea not related to pain. One hundred and fourteen episodes of concomitant pain and nausea were recorded in 61 patients (58.6 per cent). The intravenous injection of morphine or ketobemidone relieved nausea as well as pain in 80 per cent of the episodes. Relief of pain with persistence of nausea was uncommon and if pain relief was inadequate nausea was unabated. Nausea was provoked by 3.4 per cent of the morphine injections, but all patients tolerated similar doses of morphine on other occasions without nausea. Nausea often accompanies pain in the early postoperative period and can be relieved concomitant with the pain by the intravenous use of opiates in adequate doses in a high proportion of cases.", "contents": "Pain as a major cause of postoperative nausea. The incidence of nausea in relation to pain was recorded in 104 patients after abdominal operations. Ten per cent of the patients had episodes of nausea not related to pain. One hundred and fourteen episodes of concomitant pain and nausea were recorded in 61 patients (58.6 per cent). The intravenous injection of morphine or ketobemidone relieved nausea as well as pain in 80 per cent of the episodes. Relief of pain with persistence of nausea was uncommon and if pain relief was inadequate nausea was unabated. Nausea was provoked by 3.4 per cent of the morphine injections, but all patients tolerated similar doses of morphine on other occasions without nausea. Nausea often accompanies pain in the early postoperative period and can be relieved concomitant with the pain by the intravenous use of opiates in adequate doses in a high proportion of cases."}
{"id": "PMID:7352", "title": "Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes.", "content": "Saliva and serum electrolyte concentrations were monitored in 30 patients given a course of xerostomia-producing cancer radiotherapy. The mean flow rate of stimulated whole saliva decreased 83.3% during a 6-week treatment period. The striking reduction in saliva output was accompanied by significant increases in saliva Na+, Cl-, Ca++, Mg++ and Prot.- concentrations and by a decrease in saliva HCO3- content. The xerostomic saliva was more concentrated and had a greater salinity than the pretreatment saliva in each instance. In contrast, none of the serum electrolytes measured was significantly altered by the subtotal salivary shutdown.", "contents": "Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes. Saliva and serum electrolyte concentrations were monitored in 30 patients given a course of xerostomia-producing cancer radiotherapy. The mean flow rate of stimulated whole saliva decreased 83.3% during a 6-week treatment period. The striking reduction in saliva output was accompanied by significant increases in saliva Na+, Cl-, Ca++, Mg++ and Prot.- concentrations and by a decrease in saliva HCO3- content. The xerostomic saliva was more concentrated and had a greater salinity than the pretreatment saliva in each instance. In contrast, none of the serum electrolytes measured was significantly altered by the subtotal salivary shutdown."}
{"id": "PMID:7353", "title": "Models for depolymerizing enzymes: criteria for discrimination of models.", "content": "Several models for the action of alpha amylase have been proposed to account for the nonrandom distribution of oligosaccharides in the amylase digests of polysaccharides. The preferred-attack model attempts to account for the nonrandom distribution by assuming that the probability for bond cleavage depends upon the position of the bond in the chain. The repetitive, or multiple-attack, model suggests that the nonrandom distribution of oligosaccharides arises because an amylase can form a cage-like complex with a substrate and attack it several times during a single encounter. The multiple-enzyme or dual-site model suggests that the nonrandom yield of oligosaccharides arises from the combined action of exo- and endo-enzymes. The effects of pH, inhibitors, and substrate chain-length on enzyme action have been studied in several laboratories to determine which of the three action-patterns best describes the action of alpha amylase. The influence of these variables on product distributions or enzyme action-patterns are mathematically modeled in the Appendix. The experimental data on porcine-pancreatic alpha amylase are discussed in the light of the derivations.", "contents": "Models for depolymerizing enzymes: criteria for discrimination of models. Several models for the action of alpha amylase have been proposed to account for the nonrandom distribution of oligosaccharides in the amylase digests of polysaccharides. The preferred-attack model attempts to account for the nonrandom distribution by assuming that the probability for bond cleavage depends upon the position of the bond in the chain. The repetitive, or multiple-attack, model suggests that the nonrandom distribution of oligosaccharides arises because an amylase can form a cage-like complex with a substrate and attack it several times during a single encounter. The multiple-enzyme or dual-site model suggests that the nonrandom yield of oligosaccharides arises from the combined action of exo- and endo-enzymes. The effects of pH, inhibitors, and substrate chain-length on enzyme action have been studied in several laboratories to determine which of the three action-patterns best describes the action of alpha amylase. The influence of these variables on product distributions or enzyme action-patterns are mathematically modeled in the Appendix. The experimental data on porcine-pancreatic alpha amylase are discussed in the light of the derivations."}
{"id": "PMID:7355", "title": "Effects of angiographic contrast media on sino-atrial nodal function.", "content": "Injection of meglumine diatrizoate (Renografin-76) into the selectively perfused sinus node artery of the dog produces bradycardia which is unaltered by autonomic blockade or by changes in sinus node artery pressure. Contrast agents and other hyperosmolar substances prolong the R-R interval in proportion to their osmolarity. Selective injection of contrast media into other cannulated segments of the coronary tree produces no change in heart rate. Transfemoral arteriography, however, produces bradycardia with both right and left coronary injections. Both direct and reflex sinus node depression occur with coronary arteriography in the dog. Direct effects are mediated by hyperosmolarity.", "contents": "Effects of angiographic contrast media on sino-atrial nodal function. Injection of meglumine diatrizoate (Renografin-76) into the selectively perfused sinus node artery of the dog produces bradycardia which is unaltered by autonomic blockade or by changes in sinus node artery pressure. Contrast agents and other hyperosmolar substances prolong the R-R interval in proportion to their osmolarity. Selective injection of contrast media into other cannulated segments of the coronary tree produces no change in heart rate. Transfemoral arteriography, however, produces bradycardia with both right and left coronary injections. Both direct and reflex sinus node depression occur with coronary arteriography in the dog. Direct effects are mediated by hyperosmolarity."}
{"id": "PMID:7357", "title": "The form and function of cnidarian spirocysts. 2. Ultrastructure of the capsule tip and wall and mechanism of discharge.", "content": "The electron-dense capsule tip (apical cap) of sea anemone and coral spirocysts is of a different structure than the capsule wall. The capsule wall is composed of a double layer of fiber-like materials which cross each other at roughly right angles. The innermost layer is characterized by numerous serrations, the tips of which project into the lumen of the capsule. Within each serration, a band of finely cross-striated material encircles the capsule at right angles to its longitudinal axis. The membrane lining the lumen of the capsule appears to be continuous with the wall of the undischarged thread. The outer capsule wall layer consists of closely spaced microfilaments (cnidofilaments) which are oriented in the longitudinal axis of the capsule. The cnidofilaments appear to merge with the apical cap material. Contrary to some previous reports in the literature, it has been found that spirocysts normally discharge by eversion, as do nematocysts. The relationship of the capsule wall sub-structure to the spirocyst discharge process is discussed.", "contents": "The form and function of cnidarian spirocysts. 2. Ultrastructure of the capsule tip and wall and mechanism of discharge. The electron-dense capsule tip (apical cap) of sea anemone and coral spirocysts is of a different structure than the capsule wall. The capsule wall is composed of a double layer of fiber-like materials which cross each other at roughly right angles. The innermost layer is characterized by numerous serrations, the tips of which project into the lumen of the capsule. Within each serration, a band of finely cross-striated material encircles the capsule at right angles to its longitudinal axis. The membrane lining the lumen of the capsule appears to be continuous with the wall of the undischarged thread. The outer capsule wall layer consists of closely spaced microfilaments (cnidofilaments) which are oriented in the longitudinal axis of the capsule. The cnidofilaments appear to merge with the apical cap material. Contrary to some previous reports in the literature, it has been found that spirocysts normally discharge by eversion, as do nematocysts. The relationship of the capsule wall sub-structure to the spirocyst discharge process is discussed."}
{"id": "PMID:7364", "title": "Differential reaction of cell membrane phospholipids and proteins with chemical probes.", "content": "The major aims of this study were to determine the degree of phospholipid asymmetry and the neighbor analysis of phospholipids in different types of cell membranes. For this study a penetrating probe (FDNB), a non-penetrating probe (TNBS) and a cross-linking probe (DFDNB) were used. The reaction of hemoglobin, membrane protein and membrane PE and PS of erythrocytes with DFNB and TNBS was studied over a concentration range of 0.5 to 10 mM probe. TNBS reacts to an extremely small extend with hemoglobin over the concentration range 0.4 to 4 mM whereas FDNB reacts with hemoglobin to a very large extent (50 fold more than TNBS). The reaction of membrane protein of intact erythrocytes reaches a sharp plateau at 1 mM TNBS whereas the reaction of membrane protein goes to a much larger extent with FDNB with no plateau seen up to 4 mM FDNB. This data shows that TNBS does not significantly penetrate into the cell under our conditions whereas FDNB does penetrate into the cell. The results show that there are four fold more reactive sites on proteins localized on the inner surface of the erythrocyte membrane as compared to the outer surface. TNBS at 0.5 to 2 mM concentration does not label membrane PS and labels membrane PE to a small extent. The reaction of PE with TNBS shows an initial plateau at 2 mM probe and a second slightly higher plateau between 4 to 10 mM probe. TNBS from 0.5-2.0 mM does not react with PS, but between 3 to 10 mM concentration, a very small amount of PS reacts with TNBS. Hence above 2 mM TNBS or FDNB a perturbation occurs in the membrane such that more PE and PS are exposed and react with these probes. These results demonstrate that essentially no PS is localized on the outer surface of the membrane and only 5% of the total membrane PE is localized on the outer surface of the erythrocyte membrane. TNBS and FDNB were reacted with yeast, E. coli, and Acholeplasma cells. With yeast cells, FDNB reacts to a much larger extent with PE than does TNBS, indicating that FDNB penetrates into the cell and labels more PE molecules. With E. coli, but not with erythrocytes or yeast cells, phospholipase A activity was very pronounced at pH 8.5 giving rise to a large amount of DNP-GPE from DNP-PE. A phosphodiesterase was also present which hydrolyized DNP-GPE to DNP-ethanolamine. The multilayered structure of the E. coli cell envelop did not permit a definitive interpretation of the results. It is clear, however, that TNBS and FDNB react to a different extent with PE in this cell. The Acholeplasma membrane had no detectable PE or PS but contains amino acid esters of phosphatidylglycerol. The reaction of these components with TNBS and FDNB indicate that these aminoacyl-PG are localized on both surfaces of the membrane, with 31% being on the outer surface and 69% on the inner surface...", "contents": "Differential reaction of cell membrane phospholipids and proteins with chemical probes. The major aims of this study were to determine the degree of phospholipid asymmetry and the neighbor analysis of phospholipids in different types of cell membranes. For this study a penetrating probe (FDNB), a non-penetrating probe (TNBS) and a cross-linking probe (DFDNB) were used. The reaction of hemoglobin, membrane protein and membrane PE and PS of erythrocytes with DFNB and TNBS was studied over a concentration range of 0.5 to 10 mM probe. TNBS reacts to an extremely small extend with hemoglobin over the concentration range 0.4 to 4 mM whereas FDNB reacts with hemoglobin to a very large extent (50 fold more than TNBS). The reaction of membrane protein of intact erythrocytes reaches a sharp plateau at 1 mM TNBS whereas the reaction of membrane protein goes to a much larger extent with FDNB with no plateau seen up to 4 mM FDNB. This data shows that TNBS does not significantly penetrate into the cell under our conditions whereas FDNB does penetrate into the cell. The results show that there are four fold more reactive sites on proteins localized on the inner surface of the erythrocyte membrane as compared to the outer surface. TNBS at 0.5 to 2 mM concentration does not label membrane PS and labels membrane PE to a small extent. The reaction of PE with TNBS shows an initial plateau at 2 mM probe and a second slightly higher plateau between 4 to 10 mM probe. TNBS from 0.5-2.0 mM does not react with PS, but between 3 to 10 mM concentration, a very small amount of PS reacts with TNBS. Hence above 2 mM TNBS or FDNB a perturbation occurs in the membrane such that more PE and PS are exposed and react with these probes. These results demonstrate that essentially no PS is localized on the outer surface of the membrane and only 5% of the total membrane PE is localized on the outer surface of the erythrocyte membrane. TNBS and FDNB were reacted with yeast, E. coli, and Acholeplasma cells. With yeast cells, FDNB reacts to a much larger extent with PE than does TNBS, indicating that FDNB penetrates into the cell and labels more PE molecules. With E. coli, but not with erythrocytes or yeast cells, phospholipase A activity was very pronounced at pH 8.5 giving rise to a large amount of DNP-GPE from DNP-PE. A phosphodiesterase was also present which hydrolyized DNP-GPE to DNP-ethanolamine. The multilayered structure of the E. coli cell envelop did not permit a definitive interpretation of the results. It is clear, however, that TNBS and FDNB react to a different extent with PE in this cell. The Acholeplasma membrane had no detectable PE or PS but contains amino acid esters of phosphatidylglycerol. The reaction of these components with TNBS and FDNB indicate that these aminoacyl-PG are localized on both surfaces of the membrane, with 31% being on the outer surface and 69% on the inner surface..."}
{"id": "PMID:7367", "title": "Simplified, totally enzymatic method for determination of serum triglycerides with a centrifugal analyzer.", "content": "We describe a totally enzymatic method for determination of serum triglycerides (triacylglycerols) specifically adaptable to the CentrifiChem system. The method involves lipolysis with lipase from Rhizopus arrhizus alone and quantitation of the resulting glycerol with glycerol dehydrogenase in a kinetic, fixed-time mode. Hydrolysis by the lipase is complete, for concentrations up to at least 5.0 g/liter, in 10 min at room temperature. The unfavorable equilibrium for the oxidation of glycerol is overcome by increasing the pH and adding excess NAD+. Under these conditions the glycerol determination is linear to at least 4.0 g of glycerol per liter, as triglyceride. The test exhibits acceptable accuracy and precision, and results correlate well with those by an alternative totally enzymatic procedure. The present method is unaffected by phosphatase and a considerably simplified reagent is used.", "contents": "Simplified, totally enzymatic method for determination of serum triglycerides with a centrifugal analyzer. We describe a totally enzymatic method for determination of serum triglycerides (triacylglycerols) specifically adaptable to the CentrifiChem system. The method involves lipolysis with lipase from Rhizopus arrhizus alone and quantitation of the resulting glycerol with glycerol dehydrogenase in a kinetic, fixed-time mode. Hydrolysis by the lipase is complete, for concentrations up to at least 5.0 g/liter, in 10 min at room temperature. The unfavorable equilibrium for the oxidation of glycerol is overcome by increasing the pH and adding excess NAD+. Under these conditions the glycerol determination is linear to at least 4.0 g of glycerol per liter, as triglyceride. The test exhibits acceptable accuracy and precision, and results correlate well with those by an alternative totally enzymatic procedure. The present method is unaffected by phosphatase and a considerably simplified reagent is used."}
{"id": "PMID:7368", "title": "Measuring water content of feces by the Karl Fischer method.", "content": "We describe a technique for measuring the water content of stools by the Karl Fischer method. The analysis is based on removal of water into a mixture of methanol/chloroform (1/2), after dispersion of the stool by sonication in presence of solvent. An aliquot of the solution thus obtained is placed in themeasuring cell of a Karl Fischer apparatus and then analyzed in the classic way. We further describe the advantages of this method (odorless, precise, reproducible) in contrast to other current methods. In addition the same organic solution can also be used in determining the lipid content of stools.", "contents": "Measuring water content of feces by the Karl Fischer method. We describe a technique for measuring the water content of stools by the Karl Fischer method. The analysis is based on removal of water into a mixture of methanol/chloroform (1/2), after dispersion of the stool by sonication in presence of solvent. An aliquot of the solution thus obtained is placed in themeasuring cell of a Karl Fischer apparatus and then analyzed in the classic way. We further describe the advantages of this method (odorless, precise, reproducible) in contrast to other current methods. In addition the same organic solution can also be used in determining the lipid content of stools."}
{"id": "PMID:7369", "title": "Stability and precision of a new ampuled quality-control system for pH and blood-gas measurements.", "content": "We describe an evaluation of the in-use stability and short-term precision of a three-level ampuled quality-control system for monitoring pH, pCO2, and pO2 measurements on clinical blood-gas analyzers. In three hospital laboratories, 324 such ampuls were opened and allowed to stand with their contents exposed to atmospheric conditions for accurately timed intervals up to 240 s. Contents were then analyzed for pH, pCO2, and pO2. Student's t-test was used to evaluate the significance of differences observed in recoveries after time exposure. At a signifcance level of P less than or equal to 0.05, the only significant changes observed throughout the first minute of exposure were average pO2 increases of 180 Pa (1.4 mmHg) (+ 1.4%) and 230 Pa (1.7 mmHg) (+ 2.9%) at levels of 13.4 and 7.7 kPa kPa (101 and 58 mmHg), respectively. The ampuled system was found to be stable precise convenient, and suitable for use in the routine laboratory.", "contents": "Stability and precision of a new ampuled quality-control system for pH and blood-gas measurements. We describe an evaluation of the in-use stability and short-term precision of a three-level ampuled quality-control system for monitoring pH, pCO2, and pO2 measurements on clinical blood-gas analyzers. In three hospital laboratories, 324 such ampuls were opened and allowed to stand with their contents exposed to atmospheric conditions for accurately timed intervals up to 240 s. Contents were then analyzed for pH, pCO2, and pO2. Student's t-test was used to evaluate the significance of differences observed in recoveries after time exposure. At a signifcance level of P less than or equal to 0.05, the only significant changes observed throughout the first minute of exposure were average pO2 increases of 180 Pa (1.4 mmHg) (+ 1.4%) and 230 Pa (1.7 mmHg) (+ 2.9%) at levels of 13.4 and 7.7 kPa kPa (101 and 58 mmHg), respectively. The ampuled system was found to be stable precise convenient, and suitable for use in the routine laboratory."}
{"id": "PMID:7370", "title": "Determination of oxalic acid in urine by atomic absorption spectrophotometry.", "content": "A method is described for determination of oxalic acid in urine using atomic absorption spectrophotometry. The concentration of urinary oxalic acid is calculated by using the difference between two determinations of calcium: first, the excess of calcium in the supernatant after precipitation as calcium oxalate at pH 5, and second, the total calcium determined at pH less than 1 (endogenous and added). Analytical parameters (pH of precipitation, temperature, calcium and oxalate added, precipitation time, interfering substances) were studied with the aid of [14C]oxalic acid. A constant recovery of 95% of total oxalic acid allows the use of a correction factor. The accuracy and reproducibility of the method make it useful for routine determination of urinary oxalic acid.", "contents": "Determination of oxalic acid in urine by atomic absorption spectrophotometry. A method is described for determination of oxalic acid in urine using atomic absorption spectrophotometry. The concentration of urinary oxalic acid is calculated by using the difference between two determinations of calcium: first, the excess of calcium in the supernatant after precipitation as calcium oxalate at pH 5, and second, the total calcium determined at pH less than 1 (endogenous and added). Analytical parameters (pH of precipitation, temperature, calcium and oxalate added, precipitation time, interfering substances) were studied with the aid of [14C]oxalic acid. A constant recovery of 95% of total oxalic acid allows the use of a correction factor. The accuracy and reproducibility of the method make it useful for routine determination of urinary oxalic acid."}
{"id": "PMID:7371", "title": "Assessment of the functional activity of human lymphocytes in malignant disease by the local graft-versus-host reaction in rats and the T rosette-forming cell test.", "content": "The local graft-versus-host reaction (GVHR) and the spontaneous rosette-forming cell (RFC) test were used to test the functional activity of lymphocytes in blood obtained from twenty normal donors and thirty patients with malignant tumours. The lymphocytes of all twenty control donors gave a positive GVHR and had normal RFC values. In twenty-two of the thirty patients with malignancies the GVHR was negative; of these, only five had low RFC values. In the remaining eight patients the GVHR was positive and RFC values were normal. It is concluded that the local GVHR constitutes a sensitive test for measurement of the functional activity of lymphocytes, while the RFC test can only be used as a quantitative test.", "contents": "Assessment of the functional activity of human lymphocytes in malignant disease by the local graft-versus-host reaction in rats and the T rosette-forming cell test. The local graft-versus-host reaction (GVHR) and the spontaneous rosette-forming cell (RFC) test were used to test the functional activity of lymphocytes in blood obtained from twenty normal donors and thirty patients with malignant tumours. The lymphocytes of all twenty control donors gave a positive GVHR and had normal RFC values. In twenty-two of the thirty patients with malignancies the GVHR was negative; of these, only five had low RFC values. In the remaining eight patients the GVHR was positive and RFC values were normal. It is concluded that the local GVHR constitutes a sensitive test for measurement of the functional activity of lymphocytes, while the RFC test can only be used as a quantitative test."}
{"id": "PMID:7373", "title": "Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension.", "content": "The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA.", "contents": "Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension. The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA."}
{"id": "PMID:7374", "title": "Effects of prazosin in patients with hypertension.", "content": "A double-blind placebo crossover trail (2 periods, each of 6 wk) was carried out in 12 patients. In the first period the patients were randomly allocated to either their individual established dose of prazosin or to the same number of placebo tablets; treatment was reversed after 6 wk. Blood pressure was higher by 17/8 mm Hgin the lying posture and by 24/14 mm Hg in the standing posture during placebo than during prazosin treatment. Standing pulse rate and body weight were higher and plasma renin activity lower during prazosin treatment. Postural hypotension occurring 1 to 2 hr after the first few doses was noted in one third of the patients when they resumed prazosin treatment after the placebo course.", "contents": "Effects of prazosin in patients with hypertension. A double-blind placebo crossover trail (2 periods, each of 6 wk) was carried out in 12 patients. In the first period the patients were randomly allocated to either their individual established dose of prazosin or to the same number of placebo tablets; treatment was reversed after 6 wk. Blood pressure was higher by 17/8 mm Hgin the lying posture and by 24/14 mm Hg in the standing posture during placebo than during prazosin treatment. Standing pulse rate and body weight were higher and plasma renin activity lower during prazosin treatment. Postural hypotension occurring 1 to 2 hr after the first few doses was noted in one third of the patients when they resumed prazosin treatment after the placebo course."}
{"id": "PMID:7375", "title": "Blood levels and electroencephalographic effects of diazepam and bromazepam.", "content": "Blood levels and electroencephalographic (EEG) data were collected for 2 hr after single oral doses of bromazepam (9 mg), diazepam (10 mg), and placebo in 13 male adult volunteers. Both drugs caused an increase in beta activity (above 13 Hz) and a decrease in alpha activity (9 to 11 Hz) in the EEG. Blood levels of 100 ng/ml of diazepam or 50 ng/ml of bromazepam were associated with significant changes in EEG beta activity. Temporal changes in the EEG after administration of diazepam or bromazepam paralleled development of plasma levels of these drugs. Although a weakly significant correlation was found between measurable diazepam blood levels and amount of increased EEG beta activity, the relationship between measurable bromazepam blood levels and the degree of EEG changes was not significant. Quantitative EEG is a sensitive continuous response measure, useful in defining cerebral activity, response latency, and relative potency of psychoactive benzodiazepines.", "contents": "Blood levels and electroencephalographic effects of diazepam and bromazepam. Blood levels and electroencephalographic (EEG) data were collected for 2 hr after single oral doses of bromazepam (9 mg), diazepam (10 mg), and placebo in 13 male adult volunteers. Both drugs caused an increase in beta activity (above 13 Hz) and a decrease in alpha activity (9 to 11 Hz) in the EEG. Blood levels of 100 ng/ml of diazepam or 50 ng/ml of bromazepam were associated with significant changes in EEG beta activity. Temporal changes in the EEG after administration of diazepam or bromazepam paralleled development of plasma levels of these drugs. Although a weakly significant correlation was found between measurable diazepam blood levels and amount of increased EEG beta activity, the relationship between measurable bromazepam blood levels and the degree of EEG changes was not significant. Quantitative EEG is a sensitive continuous response measure, useful in defining cerebral activity, response latency, and relative potency of psychoactive benzodiazepines."}
{"id": "PMID:7376", "title": "The influence of food on nitrofurantoin bioavailability.", "content": "The effect of food on the absorption of five commercial dosage forms of nitrofurantoin varying widely in drug release and dissolution characteristics was assessed in man after oral administration. Four healthy fasting and nonfasting male subjects received, in a crossover fashion, a single 100-mg dose of microcrystalline nitrofurantoin as an aqueous suspension, three different compressed tablets, and a single 100-mg dose of macrocrystalline nitrofurantoin in a capsule. Both the absorption and the duration of therapeutic urinary concentrations of nitrofurantoin were significantly increased after administration of the five products to nonfasting subjects. The enhancement in the bioavailability of the drug in the presence of food ranged from 20% to 400%, with the greatest absorption-enhancing effect occurring with those dosage forms exhibiting the poorest dissolution characteristics. It is concluded that single-dose comparative bioavailability studies of drug products normally administered with food should be performed in both nonfasting and fasting subjects.", "contents": "The influence of food on nitrofurantoin bioavailability. The effect of food on the absorption of five commercial dosage forms of nitrofurantoin varying widely in drug release and dissolution characteristics was assessed in man after oral administration. Four healthy fasting and nonfasting male subjects received, in a crossover fashion, a single 100-mg dose of microcrystalline nitrofurantoin as an aqueous suspension, three different compressed tablets, and a single 100-mg dose of macrocrystalline nitrofurantoin in a capsule. Both the absorption and the duration of therapeutic urinary concentrations of nitrofurantoin were significantly increased after administration of the five products to nonfasting subjects. The enhancement in the bioavailability of the drug in the presence of food ranged from 20% to 400%, with the greatest absorption-enhancing effect occurring with those dosage forms exhibiting the poorest dissolution characteristics. It is concluded that single-dose comparative bioavailability studies of drug products normally administered with food should be performed in both nonfasting and fasting subjects."}
{"id": "PMID:7377", "title": "Tricyclic antidepressant overdosage: experimental studies on the management of circulatory complications.", "content": "Tricyclic antidepressant overdosage may be complicated by cardiac arrhythmias, which were sometimes difficult to treat prior to the use of sodium bicarbonate. Experiments have been done with several antiarrhythmics in an attempt to define the optimum treatment. Sodium bicarbonate proved the most effective experimentally and this supports our clinical experience. Physostigmine is a useful second drug, having beneficial effects against arrhythmias and central nervous system manifestations of toxicity. Practolol, although reversing the arrhythmias, tends to cause hypotension. Other drugs tried were less effective.", "contents": "Tricyclic antidepressant overdosage: experimental studies on the management of circulatory complications. Tricyclic antidepressant overdosage may be complicated by cardiac arrhythmias, which were sometimes difficult to treat prior to the use of sodium bicarbonate. Experiments have been done with several antiarrhythmics in an attempt to define the optimum treatment. Sodium bicarbonate proved the most effective experimentally and this supports our clinical experience. Physostigmine is a useful second drug, having beneficial effects against arrhythmias and central nervous system manifestations of toxicity. Practolol, although reversing the arrhythmias, tends to cause hypotension. Other drugs tried were less effective."}
{"id": "PMID:7385", "title": "Synaptic transmission from photoreceptors to bipolar and horizontal cells in the carp retina.", "content": "The most important observations in the present study can be summarized as follows: 1. In horizontal and bipolar cells, blocking chemical transmission caused membrane potential changes of the same polarity as the responses to illumination in each cell type. 2. Acceleration of transmitter release from the receptor terminals depolarized the horizontal cells, which is the opposite polarity to the light response. 3. Stimulation by transretinal current flowing from receptor side to vitreous side depolarized the receptor terminals and triggered transmitter release, which in turn evoked transient postsynaptic potentials in horizontal and bipolar cells. The polarity of the postsynaptic responses was the opposite to that of the light-evoked responses in each type of cell. 4. Hyperpolarization of the receptor terminals by the current of relatively long duration flowing from vitreous side to receptor side reduced the transmitter release, as demonstrated by the horizontal cell hyperpolarization. 5. From these observations, it is inferred that the receptors release the transmitter in the dark and that the transmission depolarizes horizontal and off-center bipolar cells by increasing membrane permeability chiefly to Na+ and hyperpolarizes the on-center bipolar cell by decreasing membrane permeability to Na+.", "contents": "Synaptic transmission from photoreceptors to bipolar and horizontal cells in the carp retina. The most important observations in the present study can be summarized as follows: 1. In horizontal and bipolar cells, blocking chemical transmission caused membrane potential changes of the same polarity as the responses to illumination in each cell type. 2. Acceleration of transmitter release from the receptor terminals depolarized the horizontal cells, which is the opposite polarity to the light response. 3. Stimulation by transretinal current flowing from receptor side to vitreous side depolarized the receptor terminals and triggered transmitter release, which in turn evoked transient postsynaptic potentials in horizontal and bipolar cells. The polarity of the postsynaptic responses was the opposite to that of the light-evoked responses in each type of cell. 4. Hyperpolarization of the receptor terminals by the current of relatively long duration flowing from vitreous side to receptor side reduced the transmitter release, as demonstrated by the horizontal cell hyperpolarization. 5. From these observations, it is inferred that the receptors release the transmitter in the dark and that the transmission depolarizes horizontal and off-center bipolar cells by increasing membrane permeability chiefly to Na+ and hyperpolarizes the on-center bipolar cell by decreasing membrane permeability to Na+."}
{"id": "PMID:7432", "title": "Anxiety therapy in the neoplastic patient.", "content": "A clinical study was carried out in 73 neoplastic patients suffering from anxiety and other emotional upsets to assess the effectiveness and tolerance of lorazepam. Patients  were given individualised daily doses ranging from 1.5 mg to 3 mg lorazepam for 15 to 60 days. Results, as assessed by the response of anxiety, tension, erethism and insomnia, showed that only 4 (5%) patients failed to obtain some relief. There was complete disappearance of all symptoms in 29 (40%) after 15 days, relief of at least one major symptom and reduction in the others in 27 (37%), and slight reduction in one or more symptoms in 13 (18%) patients. Side-effects were minimal and disappeared within a few days with continued treatment.", "contents": "Anxiety therapy in the neoplastic patient. A clinical study was carried out in 73 neoplastic patients suffering from anxiety and other emotional upsets to assess the effectiveness and tolerance of lorazepam. Patients  were given individualised daily doses ranging from 1.5 mg to 3 mg lorazepam for 15 to 60 days. Results, as assessed by the response of anxiety, tension, erethism and insomnia, showed that only 4 (5%) patients failed to obtain some relief. There was complete disappearance of all symptoms in 29 (40%) after 15 days, relief of at least one major symptom and reduction in the others in 27 (37%), and slight reduction in one or more symptoms in 13 (18%) patients. Side-effects were minimal and disappeared within a few days with continued treatment."}
{"id": "PMID:7438", "title": "Transport of ions and water across the epithelium of fish gills.", "content": "The teleostean gill is characterized by an exceptionally low permeability to water. Water moves along the osmotic gradient across the gill, being gained in fresh water and lost in sea water. Coupling of water movement to solute movement has not been reported. In fresh water, the gill is the site of independent active uptake of sodium and chloride. Na+ uptake is coupled to H+ or NH4+ excretion, Cl- uptake to HCO3- excretion. Amiloride blocks sodium transport and thiocyanate inhibits the chloride pump. In sea water, sodium and chloride exchanges across the gill are about 100 times faster than in fresh water, up to 100% of the internal sodium or chloride being exchanged per hour. Chloride is actively excreted, while sodium movement may well be passive. The chloride pump is associated with a mechanism for Na/K exchange; both pump and Na/K exchange are blocked by thiocyanate and possibly by ouabain. Three enzymes are involved in the ionic pumps: carbonate dehydratase (EC 4.2.1.1; carbonic anhydrase), sodium/potassium-stimulated adenosine-triphosphatase (EC 3.6.1.3, ATPase) and anion-stimulated ATPase. Specialized cells ('chloride cells') are presumably the site of the active transport.", "contents": "Transport of ions and water across the epithelium of fish gills. The teleostean gill is characterized by an exceptionally low permeability to water. Water moves along the osmotic gradient across the gill, being gained in fresh water and lost in sea water. Coupling of water movement to solute movement has not been reported. In fresh water, the gill is the site of independent active uptake of sodium and chloride. Na+ uptake is coupled to H+ or NH4+ excretion, Cl- uptake to HCO3- excretion. Amiloride blocks sodium transport and thiocyanate inhibits the chloride pump. In sea water, sodium and chloride exchanges across the gill are about 100 times faster than in fresh water, up to 100% of the internal sodium or chloride being exchanged per hour. Chloride is actively excreted, while sodium movement may well be passive. The chloride pump is associated with a mechanism for Na/K exchange; both pump and Na/K exchange are blocked by thiocyanate and possibly by ouabain. Three enzymes are involved in the ionic pumps: carbonate dehydratase (EC 4.2.1.1; carbonic anhydrase), sodium/potassium-stimulated adenosine-triphosphatase (EC 3.6.1.3, ATPase) and anion-stimulated ATPase. Specialized cells ('chloride cells') are presumably the site of the active transport."}
{"id": "PMID:7439", "title": "Coupling of water to solute movement in isolated gastric mucosa.", "content": "Osmosis is apparently the mechanism responsible for the coupling of water to solute transport in biological membranes. Often a secreted or absorbed fluid is essentially iso-osmotic with the solution of origin, or with plasma, and various models have been constructed by Curran, Diamond and others to account for such observations. More information is needed, however, to test further the predictions of these models and to facilitate correlation with known structural details. This study deals with gastric secretion and the effects of the luminal solution on its composition. Although pure gastric juice collected in vivo is virtually iso-osmotic with plasma, Teorell, Obrink and others found that instillation of a buffer solution (glycine) in the lumen led to a twofold increase in the concentration of gastric acid. This effect is not restricted to buffer solutions: the normality of H+ secreted into an isotonic (120 mM) NaCl solution bathing the isolated bullfrog gastric mucosa was 276 +/- 19 mmol/1 (13 experiments). Clearly the luminal solution affects the concentration of gastric secretion, probably by reducing an endogenous osmotic gradient. Thus the sites responsible for transport of H+ must be accessible from the luminal solution.", "contents": "Coupling of water to solute movement in isolated gastric mucosa. Osmosis is apparently the mechanism responsible for the coupling of water to solute transport in biological membranes. Often a secreted or absorbed fluid is essentially iso-osmotic with the solution of origin, or with plasma, and various models have been constructed by Curran, Diamond and others to account for such observations. More information is needed, however, to test further the predictions of these models and to facilitate correlation with known structural details. This study deals with gastric secretion and the effects of the luminal solution on its composition. Although pure gastric juice collected in vivo is virtually iso-osmotic with plasma, Teorell, Obrink and others found that instillation of a buffer solution (glycine) in the lumen led to a twofold increase in the concentration of gastric acid. This effect is not restricted to buffer solutions: the normality of H+ secreted into an isotonic (120 mM) NaCl solution bathing the isolated bullfrog gastric mucosa was 276 +/- 19 mmol/1 (13 experiments). Clearly the luminal solution affects the concentration of gastric secretion, probably by reducing an endogenous osmotic gradient. Thus the sites responsible for transport of H+ must be accessible from the luminal solution."}
{"id": "PMID:7440", "title": "Ion transport across amphibian lung.", "content": "The simple architecture of the amphibian lung makes it possible to study the movement of substances across a barrier with permeability and bioelectric properties that are dominated by the alveolar epithelium. When mounted as a planar sheet between identical Ringer solutions the excised lung of the bullfrog exhibited a transmural electrical potential difference of nearly 20 mV (pleural surface positive) and a resistance of about 700 omega cm2. Unidirectional fluxes of 36Cl, Br-, I-, and SCN- across the short-circuited lung were asymmetrical. The net 36Cl- flow from pleura to lumen matched the short-circuit current after 1.5 h of voltage clamping, followed the kinetics of a saturable process, and was reduced by inhibitors of oxidative metabolism. These results suggest that halide and certain pseudohalide anions are secreted by the frog alveolar epithelium. Fluxes of Na+, K+, Ca+, HCO3-, TcO4-, SO42-, p-aminohippurate, gluconate, dinitrophenolate and water were compatible with passive diffusion of the probe molecules across the barrier. Measurements of lung oxygen consumption, ion fluxes and bioelectric properties have helped to pinpoint possible sites and modes of action of airborne agents, such as heavy metals, sulphates and nitrates, that may damage the mammalian pulmonary barrier.", "contents": "Ion transport across amphibian lung. The simple architecture of the amphibian lung makes it possible to study the movement of substances across a barrier with permeability and bioelectric properties that are dominated by the alveolar epithelium. When mounted as a planar sheet between identical Ringer solutions the excised lung of the bullfrog exhibited a transmural electrical potential difference of nearly 20 mV (pleural surface positive) and a resistance of about 700 omega cm2. Unidirectional fluxes of 36Cl, Br-, I-, and SCN- across the short-circuited lung were asymmetrical. The net 36Cl- flow from pleura to lumen matched the short-circuit current after 1.5 h of voltage clamping, followed the kinetics of a saturable process, and was reduced by inhibitors of oxidative metabolism. These results suggest that halide and certain pseudohalide anions are secreted by the frog alveolar epithelium. Fluxes of Na+, K+, Ca+, HCO3-, TcO4-, SO42-, p-aminohippurate, gluconate, dinitrophenolate and water were compatible with passive diffusion of the probe molecules across the barrier. Measurements of lung oxygen consumption, ion fluxes and bioelectric properties have helped to pinpoint possible sites and modes of action of airborne agents, such as heavy metals, sulphates and nitrates, that may damage the mammalian pulmonary barrier."}
{"id": "PMID:7441", "title": "Ion transport and water flow in the mammalian lung.", "content": "The coupling of bulk water flow to active ion transport has been described in various epithelia; evidence presented here suggests that this is also a feature of the mammalian lung. Measurements of the ionic composition of lung liquid and its rate of formation in the fetal lamb in vivo have made it possible to estimate the net flux of each ion and, with water tracer measurements of ion one-way fluxes, to calculate flux ratios. When these are compared with the ratios predicted by the Ussing flux ratio equation it is clear that the secretion of lung liquid is linked to active transport of Cl- from plasma; sodium moves passively. In addition there is an apparent uphill transfer of HCO2- out of lung liquid. In an in vitro preparation of adult canine trachea Cl- is actively transported towards the lumen and is associated with a small net flux of Na+ in the opposite direction. Addition of acetylcholine increases the net Cl- flux towards the lumen but reverses the orientation of the net Na+ flux. Changes such as these may be important determinants of bulk liquid flow in vivo as well as in vitro.", "contents": "Ion transport and water flow in the mammalian lung. The coupling of bulk water flow to active ion transport has been described in various epithelia; evidence presented here suggests that this is also a feature of the mammalian lung. Measurements of the ionic composition of lung liquid and its rate of formation in the fetal lamb in vivo have made it possible to estimate the net flux of each ion and, with water tracer measurements of ion one-way fluxes, to calculate flux ratios. When these are compared with the ratios predicted by the Ussing flux ratio equation it is clear that the secretion of lung liquid is linked to active transport of Cl- from plasma; sodium moves passively. In addition there is an apparent uphill transfer of HCO2- out of lung liquid. In an in vitro preparation of adult canine trachea Cl- is actively transported towards the lumen and is associated with a small net flux of Na+ in the opposite direction. Addition of acetylcholine increases the net Cl- flux towards the lumen but reverses the orientation of the net Na+ flux. Changes such as these may be important determinants of bulk liquid flow in vivo as well as in vitro."}
{"id": "PMID:7442", "title": "Lung carbonate dehydratase (carbonic anhydrase), CO2 stores and CO2 transport.", "content": "A study of CO2 storage in excised, exsanguinated lungs revealed that CO2 stores include a compartment which reaches equilibration very rapidly (less than 3s) and a slower compartment which equilibrates with a half-time of approximately 15 s. Inhibition of carbonate dehydratase (carbonic anhydrase, EC 4.2.1.1) does not change the slope of the total CO2 dissociation curve of the lung but does increase the slow compartment at the expense of the fast. CO2 diffusion across the pleura is approximately 20 times faster than that of O2, a relationship that is not affected by inhibition of carbonate dehydratase. The role of tissue CO2 stores in limiting respiratory fluctuations of PCO2 or pH in arterial blood is only minor and may be of significance only in rapid, deep inspiration. CO2 uptake or release by the stores is out of phase with blood CO2 exchange. As a consequence, the time course of CO2 exchange at the mouth during expiration cannot be used to predict alveolar or capillary CO2 exchange.", "contents": "Lung carbonate dehydratase (carbonic anhydrase), CO2 stores and CO2 transport. A study of CO2 storage in excised, exsanguinated lungs revealed that CO2 stores include a compartment which reaches equilibration very rapidly (less than 3s) and a slower compartment which equilibrates with a half-time of approximately 15 s. Inhibition of carbonate dehydratase (carbonic anhydrase, EC 4.2.1.1) does not change the slope of the total CO2 dissociation curve of the lung but does increase the slow compartment at the expense of the fast. CO2 diffusion across the pleura is approximately 20 times faster than that of O2, a relationship that is not affected by inhibition of carbonate dehydratase. The role of tissue CO2 stores in limiting respiratory fluctuations of PCO2 or pH in arterial blood is only minor and may be of significance only in rapid, deep inspiration. CO2 uptake or release by the stores is out of phase with blood CO2 exchange. As a consequence, the time course of CO2 exchange at the mouth during expiration cannot be used to predict alveolar or capillary CO2 exchange."}
{"id": "PMID:7446", "title": "Prolactin-releasing and release-inhibiting factor activities in the bovine, rat, and human pineal gland: in vitro and in vivo studies.", "content": "The effects of crude extracts of bovine, rat, and human pineal glands on prolactin (PRL) release were studied using an in vitro system. In addition, the effects of a known pineal constituent, arginine vasotocin (AVT), and crude bovine pineal extract (bPE) on PRL secretion were studied in vivo. Normal male rat hemipituitaries (HP), incubated with bPE (13 mg tissue/HP)released 200%, 150%, and 285% more PRL into the medium than did their corresponding untreated control halves incubated in either Medium 199 alone, hypothalamic extract, or cerebral cortical extract, respectively. HP incubated with either rat (6 mg of tissue/HP) or human (25 mg of tissue/HP) pineal extract released 110% and 75% more PRL, respectively, than did their corresponding untreated control halves. HP exposed to 10 mg tissue eq of either bovine pineal fraction A1 or bovine pineal fraction A3 released 88% and 63%, respectively, less PRL than did their corresponding untreated control halves incubated in Krebs-Ringer Bicarbonate (KRB) medium. Quantitites of melatonin, thyrotropin-releasing hormone (TRH), or estrogen, comparable to those found in the pineal, had no significant effect on PRL secretion in vitro. The iv injection of either bPE (90 mg tissue/rat) or AVT (10 mug/rat) into estrogen and progesterone-treated male rats resulted in a 40% and 138% increase, respectively, in plasma PRL titers, 10 min after injection, over pre-injection control levels. The per cent of increase in plasma PRL levels in these animals was significantly greater than that observed in control rats receiving either saline or cortical extract. The results suggest that crude extracts of pineal glands of three different species contain prolactin-releasing factor (PRF) activity which is probably not due to any endogenous melatonin, TRH, or estrogen that may be present. Conversely, two bovine pineal fractions, A1 and A3, appeared to exhibit prolactin-inhibiting factor (PIF) activity. We have concluded that the pineal gland may serve as an alternate or supplemental source of PRF and/or PIF.", "contents": "Prolactin-releasing and release-inhibiting factor activities in the bovine, rat, and human pineal gland: in vitro and in vivo studies. The effects of crude extracts of bovine, rat, and human pineal glands on prolactin (PRL) release were studied using an in vitro system. In addition, the effects of a known pineal constituent, arginine vasotocin (AVT), and crude bovine pineal extract (bPE) on PRL secretion were studied in vivo. Normal male rat hemipituitaries (HP), incubated with bPE (13 mg tissue/HP)released 200%, 150%, and 285% more PRL into the medium than did their corresponding untreated control halves incubated in either Medium 199 alone, hypothalamic extract, or cerebral cortical extract, respectively. HP incubated with either rat (6 mg of tissue/HP) or human (25 mg of tissue/HP) pineal extract released 110% and 75% more PRL, respectively, than did their corresponding untreated control halves. HP exposed to 10 mg tissue eq of either bovine pineal fraction A1 or bovine pineal fraction A3 released 88% and 63%, respectively, less PRL than did their corresponding untreated control halves incubated in Krebs-Ringer Bicarbonate (KRB) medium. Quantitites of melatonin, thyrotropin-releasing hormone (TRH), or estrogen, comparable to those found in the pineal, had no significant effect on PRL secretion in vitro. The iv injection of either bPE (90 mg tissue/rat) or AVT (10 mug/rat) into estrogen and progesterone-treated male rats resulted in a 40% and 138% increase, respectively, in plasma PRL titers, 10 min after injection, over pre-injection control levels. The per cent of increase in plasma PRL levels in these animals was significantly greater than that observed in control rats receiving either saline or cortical extract. The results suggest that crude extracts of pineal glands of three different species contain prolactin-releasing factor (PRF) activity which is probably not due to any endogenous melatonin, TRH, or estrogen that may be present. Conversely, two bovine pineal fractions, A1 and A3, appeared to exhibit prolactin-inhibiting factor (PIF) activity. We have concluded that the pineal gland may serve as an alternate or supplemental source of PRF and/or PIF."}
{"id": "PMID:7447", "title": "Adenylyl cyclase activities in ovarian tissues. I. Homogenization and conditions of assay in graafian follicles and corpora lutea of rabbits, rats, and pigs: regulation by ATP, and some comparative properties.", "content": "Responsiveness of ovarian adenylyl cyclases to luteinizing hormone (LH), found to be 5 to 10-fold in cell-free preparations under optimal conditions, required gentle homogenizations and storage in sucrose-containing media. Assay conditions required the use of an ATP-regenerating system consisting of creatine kinase, creatine phosphate, and myokinase for the preservation of ATP levels. LH-stimulated adenylyl cyclase (AC) in rabbit CL showed the following properties: 1) The pH optimum of basal activity was about 8.0; that of LH-stimulated activity was about 7.5. 2) The relative response to LH was low (1.5 to 2-fold) at 0.1 mM ATP and increased with increasing ATP, but not with increasing GTP. At low (0.1 mM) ATP, GTP increased catalytic efficacy of the system, both in the absence and in the presence of LH (no effect on relative stimulation). 3) The optimal relative stimulation by LH was obtained at about 1.0 mM MgCl2 in excess of added magnesium-binding ingredients. 4) The sensitivity to stimulation by LH (about 0.2 mug/ml NIH-LH-B8) was unaffected by either pH, nucleotides (ATP and GTP), or MgCl2 concentration. 5) Under the assay conditions used, activity was stimulated by prostaglandin E1 (PGE1) about 1.5 to 2-fold, and by epinephrine about 3 to 4-fold. In all aspects tested, LH-stimulated AC in rat CL resembled that in rabbit CL, except that about 5-fold higher concentrations of NIH-LH-B8 were needed for half-maximal stimulation. The AC activity in pig Graafian follicles, however, differed from that in rabbit CL in that 1) the ATP concentration needed for optimal stimulation by LH was lower (in the micromolar rather than the millimolar range); 2) catecholamines elicited only a 1.3 to 1.4-fold stimulation; and 3) NIH-LH-B8 elicited half-maximal stimulation at 0.008 to 0.020 mug/ml. We were unable to detect LH-responsive AC activity in either homogenates or washed particles of CL from either cycling or pregnant pigs. LH fractions of three origins (human, bovine, and ovine) and of varying specific activities (from 0.041 to 2.0 NIH-LH-S18 units/mg) were tested and the relative potencies by OAAD assay were found to correlate well with the relative potencies in the adenylyl cyclase assays (rat CL, rabbit CL, and pig follicles), consistent with the possibility that AC receptors are responsible for biologic actions of LH.", "contents": "Adenylyl cyclase activities in ovarian tissues. I. Homogenization and conditions of assay in graafian follicles and corpora lutea of rabbits, rats, and pigs: regulation by ATP, and some comparative properties. Responsiveness of ovarian adenylyl cyclases to luteinizing hormone (LH), found to be 5 to 10-fold in cell-free preparations under optimal conditions, required gentle homogenizations and storage in sucrose-containing media. Assay conditions required the use of an ATP-regenerating system consisting of creatine kinase, creatine phosphate, and myokinase for the preservation of ATP levels. LH-stimulated adenylyl cyclase (AC) in rabbit CL showed the following properties: 1) The pH optimum of basal activity was about 8.0; that of LH-stimulated activity was about 7.5. 2) The relative response to LH was low (1.5 to 2-fold) at 0.1 mM ATP and increased with increasing ATP, but not with increasing GTP. At low (0.1 mM) ATP, GTP increased catalytic efficacy of the system, both in the absence and in the presence of LH (no effect on relative stimulation). 3) The optimal relative stimulation by LH was obtained at about 1.0 mM MgCl2 in excess of added magnesium-binding ingredients. 4) The sensitivity to stimulation by LH (about 0.2 mug/ml NIH-LH-B8) was unaffected by either pH, nucleotides (ATP and GTP), or MgCl2 concentration. 5) Under the assay conditions used, activity was stimulated by prostaglandin E1 (PGE1) about 1.5 to 2-fold, and by epinephrine about 3 to 4-fold. In all aspects tested, LH-stimulated AC in rat CL resembled that in rabbit CL, except that about 5-fold higher concentrations of NIH-LH-B8 were needed for half-maximal stimulation. The AC activity in pig Graafian follicles, however, differed from that in rabbit CL in that 1) the ATP concentration needed for optimal stimulation by LH was lower (in the micromolar rather than the millimolar range); 2) catecholamines elicited only a 1.3 to 1.4-fold stimulation; and 3) NIH-LH-B8 elicited half-maximal stimulation at 0.008 to 0.020 mug/ml. We were unable to detect LH-responsive AC activity in either homogenates or washed particles of CL from either cycling or pregnant pigs. LH fractions of three origins (human, bovine, and ovine) and of varying specific activities (from 0.041 to 2.0 NIH-LH-S18 units/mg) were tested and the relative potencies by OAAD assay were found to correlate well with the relative potencies in the adenylyl cyclase assays (rat CL, rabbit CL, and pig follicles), consistent with the possibility that AC receptors are responsible for biologic actions of LH."}
{"id": "PMID:7449", "title": "Further observations on the properties of serum and tissue guanase from man and some animal species. Optimum pH and activation energy in the presence of 8-azaguanine.", "content": "The activation energy and the optimum pH of guanine deaminase in man, the rat, guinea pig and mouse were studied using 8-azaguanine as a substrate. The serum guanase in man and in all the animal species studied differs in activation energy from the guanase of the liver. In man, moreover, the serum guanase is also different from the brain and kidney enzyme. In the rat and guinea pig the brain enzyme has thermic activation energy different from the liver and kidney enzyme. The guanase of the serum and tissues of the guinea pig differs from the enzyme of the serum and tissues of man, rat and mouse for optimum pH.", "contents": "Further observations on the properties of serum and tissue guanase from man and some animal species. Optimum pH and activation energy in the presence of 8-azaguanine. The activation energy and the optimum pH of guanine deaminase in man, the rat, guinea pig and mouse were studied using 8-azaguanine as a substrate. The serum guanase in man and in all the animal species studied differs in activation energy from the guanase of the liver. In man, moreover, the serum guanase is also different from the brain and kidney enzyme. In the rat and guinea pig the brain enzyme has thermic activation energy different from the liver and kidney enzyme. The guanase of the serum and tissues of the guinea pig differs from the enzyme of the serum and tissues of man, rat and mouse for optimum pH."}
{"id": "PMID:7450", "title": "Control of fatty-acid synthetase levels by exogeneous long-chain fatty acids in the yeasts Candida lipolytica and Saccharomyces cerevisiae.", "content": "Endogeneous fatty acid biosynthesis in the two yeast species, Saccharomyces cerevisiae and Candida lipolytica is completely repressed by the addition of long-chain fatty acids to the growth medium. In Candida lipolytica, this repression is accompanied by a corresponding loss of fatty acid synthetase activity in the cell homogenate, when the cells were grown on fatty acids as the sole carbon source. The activity of the Saccharomyces cerevisiae fatty acid synthetase, however, remains unaffected by the addition of fatty acids to a glucose-containing growth medium. From fatty-acid-grown Candida lipolytica cells no fatty acid synthetase complex can be isolated, nor is there any immunologically cross-reacting fatty acid synthetase protein detectable in the crude cell extract. From this it is concluded that Candida lipolytica, but not Saccharomyces cerevisiae, is able to adapt to the growth on fatty acids either by repression of fatty acid synthetase biosynthesis or by a fatty-acid-induced proteolytic degradation of the multienzyme complex. Similarly, the fatty acid synthetase complex disappears rapidly from stationary phase Candida lipolytica cells even after growth in fatty-acid-free medium. Finally, it was found that the fatty acid synthetase complexes from Saccharomyces cerevisiae and Candida lipolytica, though very similar in size and subunit composition, were immunologically different and had no common antigenic determinants.", "contents": "Control of fatty-acid synthetase levels by exogeneous long-chain fatty acids in the yeasts Candida lipolytica and Saccharomyces cerevisiae. Endogeneous fatty acid biosynthesis in the two yeast species, Saccharomyces cerevisiae and Candida lipolytica is completely repressed by the addition of long-chain fatty acids to the growth medium. In Candida lipolytica, this repression is accompanied by a corresponding loss of fatty acid synthetase activity in the cell homogenate, when the cells were grown on fatty acids as the sole carbon source. The activity of the Saccharomyces cerevisiae fatty acid synthetase, however, remains unaffected by the addition of fatty acids to a glucose-containing growth medium. From fatty-acid-grown Candida lipolytica cells no fatty acid synthetase complex can be isolated, nor is there any immunologically cross-reacting fatty acid synthetase protein detectable in the crude cell extract. From this it is concluded that Candida lipolytica, but not Saccharomyces cerevisiae, is able to adapt to the growth on fatty acids either by repression of fatty acid synthetase biosynthesis or by a fatty-acid-induced proteolytic degradation of the multienzyme complex. Similarly, the fatty acid synthetase complex disappears rapidly from stationary phase Candida lipolytica cells even after growth in fatty-acid-free medium. Finally, it was found that the fatty acid synthetase complexes from Saccharomyces cerevisiae and Candida lipolytica, though very similar in size and subunit composition, were immunologically different and had no common antigenic determinants."}
{"id": "PMID:7451", "title": "Calorimetric study on human erythrocyte glycolysis. Heat production in various metabolic conditions.", "content": "The heat production of human erythrocytes was measured on a flow microcalorimeter with simultaneous analyses of lactate and other metabolites. The heat production connected with the lactate formation was about 17 kcal (71 kJ) per mol lactate formed which corresponded to the sum of heat production due to the formation of lactate from glucose and the heat production due to neutralization. The heat production rate increased as the pH of the suspension increased, corresponding to the increase in lactate formation. Glycolytic inhibitors such as fluoride and monoiodoacetate caused a decrease in the rate of heat production, whereas arsenate induced a large transient increase in heat production associated with a transient increase in lactate formation. Decrease in pyruvate concentration was usually associated with increase in heat production, although the decreased pyruvate concentration was coupled with formation of 2,3-bisphosphoglycerate. When inosine, dihydroxyacetone or D-glyceraldehyde was used as a substrate, an increase in the heat production rate was observed. Addition of methylene blue caused an oxygen uptake which was accompanied by a remarkable increase in heat production rate corresponding to about 160 kcal (670 kJ) per mol oxygen consumed. The value for heat production in red cells in the above-mentioned metabolic conditions was considered in relation to earlier known data on free energy and enthalpy changes of the different metabolic steps in the glycolytic pathway.", "contents": "Calorimetric study on human erythrocyte glycolysis. Heat production in various metabolic conditions. The heat production of human erythrocytes was measured on a flow microcalorimeter with simultaneous analyses of lactate and other metabolites. The heat production connected with the lactate formation was about 17 kcal (71 kJ) per mol lactate formed which corresponded to the sum of heat production due to the formation of lactate from glucose and the heat production due to neutralization. The heat production rate increased as the pH of the suspension increased, corresponding to the increase in lactate formation. Glycolytic inhibitors such as fluoride and monoiodoacetate caused a decrease in the rate of heat production, whereas arsenate induced a large transient increase in heat production associated with a transient increase in lactate formation. Decrease in pyruvate concentration was usually associated with increase in heat production, although the decreased pyruvate concentration was coupled with formation of 2,3-bisphosphoglycerate. When inosine, dihydroxyacetone or D-glyceraldehyde was used as a substrate, an increase in the heat production rate was observed. Addition of methylene blue caused an oxygen uptake which was accompanied by a remarkable increase in heat production rate corresponding to about 160 kcal (670 kJ) per mol oxygen consumed. The value for heat production in red cells in the above-mentioned metabolic conditions was considered in relation to earlier known data on free energy and enthalpy changes of the different metabolic steps in the glycolytic pathway."}
{"id": "PMID:7452", "title": "Studies of glutamate dehydrogenase. Regulation of glutamate dehydrogenase from Candida utilis by a pH and temperature-dependent conformational transition.", "content": "Glutamate dehydrogenase from Candida utilis undergoes a reversible conformational transition between an active and an inactive state at low pH AND low temperature. This conformational transition can also be followed by fluorescence measurements. The temperature-dependent equilibrium between the active and the inactive state is characterized by a transition temperature of 10.7 degrees C and a delta H value of 148 kcal/mol (620 kJ/mol). The temperature dependence of the enzymic activity above 15 degrees C yields an activation energy of 15 kcal/mol (63 kJ/mol), a larger value than that for the beef liver enzyme (9 kcal/mol; 38 kJ/mol). In contrast to the yeast enzyme the Arrhenius plot is linear and, therefore, the beef liver enzyme is not transformed into an inactive conformation at low temperatures. Sedimentation analysis shows that the inactivation of the Candida utilis enzyme is not caused by change in the quaternary structure. The pH dependence of the conformational transition at low pH measured by fluorescence change is characterized by a pK value of 7.01 for the enzyme in the absence and of 6.89 for the enzyme in the presence of 2-oxoglutarate with a Hill coefficient of 3.4 in both cases. Similar results are found when the pH dependence of the enzymic activity is analyzed. With the beef liver enzyme the same pK value is obtained but with a Hill coefficient of 1 indicating cooperativity only in the case of the Candida utilis enzyme. The best fit of the pH dependence of the rate constants of the fluorescence changes was obtained with pK values of 7.45 and 6.45 for the active and the inactive state respectively. In this model the lowest time constant which is obtained at the pH of the equilibrium was found to be 0.05 s-1. Preincubation experiments with the substrate 2-oxoglutarate but not with the coenzyme shift the equilibrium to the active conformation. The coenzyme obviously reduces the rate constant of the conformational transition. The sedimentation coefficient (SO20, w) and the molecular weight were found to be 11.0 S and 276 000, respectively. The enzyme molecule is built up by six polypeptide chains each having a molecular weight of 47 000.", "contents": "Studies of glutamate dehydrogenase. Regulation of glutamate dehydrogenase from Candida utilis by a pH and temperature-dependent conformational transition. Glutamate dehydrogenase from Candida utilis undergoes a reversible conformational transition between an active and an inactive state at low pH AND low temperature. This conformational transition can also be followed by fluorescence measurements. The temperature-dependent equilibrium between the active and the inactive state is characterized by a transition temperature of 10.7 degrees C and a delta H value of 148 kcal/mol (620 kJ/mol). The temperature dependence of the enzymic activity above 15 degrees C yields an activation energy of 15 kcal/mol (63 kJ/mol), a larger value than that for the beef liver enzyme (9 kcal/mol; 38 kJ/mol). In contrast to the yeast enzyme the Arrhenius plot is linear and, therefore, the beef liver enzyme is not transformed into an inactive conformation at low temperatures. Sedimentation analysis shows that the inactivation of the Candida utilis enzyme is not caused by change in the quaternary structure. The pH dependence of the conformational transition at low pH measured by fluorescence change is characterized by a pK value of 7.01 for the enzyme in the absence and of 6.89 for the enzyme in the presence of 2-oxoglutarate with a Hill coefficient of 3.4 in both cases. Similar results are found when the pH dependence of the enzymic activity is analyzed. With the beef liver enzyme the same pK value is obtained but with a Hill coefficient of 1 indicating cooperativity only in the case of the Candida utilis enzyme. The best fit of the pH dependence of the rate constants of the fluorescence changes was obtained with pK values of 7.45 and 6.45 for the active and the inactive state respectively. In this model the lowest time constant which is obtained at the pH of the equilibrium was found to be 0.05 s-1. Preincubation experiments with the substrate 2-oxoglutarate but not with the coenzyme shift the equilibrium to the active conformation. The coenzyme obviously reduces the rate constant of the conformational transition. The sedimentation coefficient (SO20, w) and the molecular weight were found to be 11.0 S and 276 000, respectively. The enzyme molecule is built up by six polypeptide chains each having a molecular weight of 47 000."}
{"id": "PMID:7453", "title": "A spectroscopic investigation of S-trifluoroethylthiopapain. An investigation of the active site of papain.", "content": "The pH dependence of the 19F chemical shift and the fluorescence spectrum of S-2,2,2-trifluoro-1,1-dideuteroethyl-thio-paapain are analysed in terms of dependence on the ionisation of aspartic-acid-158 and histidine-159. The 19F probe causes negative cooperativity between these groups, and does not detected any ionisation at high pH. The intermediate chemical exchange rates for the ionisation of aspartic-acid-158 and histidine-159 allow the approxmate rate constants for proton transfer to be calculated. The rather low rate constants are explained in terms of the hydrophobicity of the active-site region and the net positive charge on the enzyme resulting from its high isoelectric point.", "contents": "A spectroscopic investigation of S-trifluoroethylthiopapain. An investigation of the active site of papain. The pH dependence of the 19F chemical shift and the fluorescence spectrum of S-2,2,2-trifluoro-1,1-dideuteroethyl-thio-paapain are analysed in terms of dependence on the ionisation of aspartic-acid-158 and histidine-159. The 19F probe causes negative cooperativity between these groups, and does not detected any ionisation at high pH. The intermediate chemical exchange rates for the ionisation of aspartic-acid-158 and histidine-159 allow the approxmate rate constants for proton transfer to be calculated. The rather low rate constants are explained in terms of the hydrophobicity of the active-site region and the net positive charge on the enzyme resulting from its high isoelectric point."}
{"id": "PMID:7454", "title": "Enzymic synthesis of lignin precursors. Purification and properties of a cinnamoyl-CoA: NADPH reductase from cell suspension cultures of soybean (Glycinemax).", "content": "A cinnamoyl-coenzyme A reductase catalyzing the NADPH-dependent reduction of substituted cinnamoyl-CoA thiol esters to the corresponding cinnamaldehydes was isolated from cell suspension cultures of soybean (Glycine max L. var. Mandarin). A 1660-fold purification of the enzyme was achieved by (NH4)2SO4 fractionation, chromatography on DEAE-cellulose, hydroxyapatite and Sephadex G-100 and affinity chromatography on 5'-AMP-Sepharose. The apparent molecular weight of the reductase was found to be about 38 000 on the basis of the elution volume from a Sephadex G-100 column. Maximum rate of reaction was observed between pH 6.0 and 6.2 in 0.1-0.2 M citrate buffer at 30 degrees C. The enzyme was markedly inhibited by thiol reagents. The reductase showed a high degree of specificity for cinnamoyl-CoA esters. Feruloyl-CoA was the substrate with the lowest Km value (73 muM) and highest V (230 nkat/mg) followed by 5-hydroxy-feruloyl-CoA, sinapoyl-CoA, p-coumaroyl-CoA, caffeoyl-CoA and cinnamoyl-CoA. No reaction took place with acetyl-CoA. The Km value for NADPH varied with the type of substrate. Km values of 28, 120, and 290 muM were found with feruloyl-CoA, sinapoyl-CoA, and p-coumaroyl-CoA, respectively. The rate of reaction observed with NADH was only about 5% of that found with NADPH. The reaction products CoASH and NADP+ inhibited the reaction. The Ki values were in the range of 0.5-1 mM and the inhibition was of a noncompetitive (mixed) type. The role of the reductase in the biosynthesis of lignin precursors is discussed.", "contents": "Enzymic synthesis of lignin precursors. Purification and properties of a cinnamoyl-CoA: NADPH reductase from cell suspension cultures of soybean (Glycinemax). A cinnamoyl-coenzyme A reductase catalyzing the NADPH-dependent reduction of substituted cinnamoyl-CoA thiol esters to the corresponding cinnamaldehydes was isolated from cell suspension cultures of soybean (Glycine max L. var. Mandarin). A 1660-fold purification of the enzyme was achieved by (NH4)2SO4 fractionation, chromatography on DEAE-cellulose, hydroxyapatite and Sephadex G-100 and affinity chromatography on 5'-AMP-Sepharose. The apparent molecular weight of the reductase was found to be about 38 000 on the basis of the elution volume from a Sephadex G-100 column. Maximum rate of reaction was observed between pH 6.0 and 6.2 in 0.1-0.2 M citrate buffer at 30 degrees C. The enzyme was markedly inhibited by thiol reagents. The reductase showed a high degree of specificity for cinnamoyl-CoA esters. Feruloyl-CoA was the substrate with the lowest Km value (73 muM) and highest V (230 nkat/mg) followed by 5-hydroxy-feruloyl-CoA, sinapoyl-CoA, p-coumaroyl-CoA, caffeoyl-CoA and cinnamoyl-CoA. No reaction took place with acetyl-CoA. The Km value for NADPH varied with the type of substrate. Km values of 28, 120, and 290 muM were found with feruloyl-CoA, sinapoyl-CoA, and p-coumaroyl-CoA, respectively. The rate of reaction observed with NADH was only about 5% of that found with NADPH. The reaction products CoASH and NADP+ inhibited the reaction. The Ki values were in the range of 0.5-1 mM and the inhibition was of a noncompetitive (mixed) type. The role of the reductase in the biosynthesis of lignin precursors is discussed."}
{"id": "PMID:7455", "title": "Interconversion between 17 beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) and 5alpha-androstane-3alpha, 17 beta-diol in rat kidney: heterogeneity of 3alpha-hydroxysteroid oxidoreductases.", "content": "3alpha-Hydroxysteroid oxidoreductases catalyzing the interconversion between 17 beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) and 5alpha-androstane-3alpha, 17 beta-diol (3alpha-androstanediol) have been studied in rat kidney. Three enzymes can be distinguished: a soluble NADPH-dependent oxidoreductase, a microsomal NADPH-dependent enzyme and a microsomal NADH-linked enzyme. Traces of the microsomal enzymes are consistently observed in the 108 000 X g supernatant. Studies on crude preparations reveal that these enzymes differ not only in subcellular localization and co-factor requirement, but also in optimum pH, kinetic characteristics, sensitivity to potential steroidal inhibitors and sensitivity to detergents, ionic strength and temperature. Moreover, salient sex differences exist in the activity of all three kidney enzymes. The soluble NADPH-dependent enzyme is more active in female rats whereas both microsomal enzymes are considerably more active in male animals. The microsomal NADH-dependent oxidoreductase displays favorable characteristics to catalyze the 3alpha-dehydrogenation of 3alpha-androstanediol. Evidence is presented that it is mainly this enzyme that enables the kidney to use 3alpha-androstanediol as an efficient precursor for the local formation of 5alpha-dihydrotestosterone.", "contents": "Interconversion between 17 beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) and 5alpha-androstane-3alpha, 17 beta-diol in rat kidney: heterogeneity of 3alpha-hydroxysteroid oxidoreductases. 3alpha-Hydroxysteroid oxidoreductases catalyzing the interconversion between 17 beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) and 5alpha-androstane-3alpha, 17 beta-diol (3alpha-androstanediol) have been studied in rat kidney. Three enzymes can be distinguished: a soluble NADPH-dependent oxidoreductase, a microsomal NADPH-dependent enzyme and a microsomal NADH-linked enzyme. Traces of the microsomal enzymes are consistently observed in the 108 000 X g supernatant. Studies on crude preparations reveal that these enzymes differ not only in subcellular localization and co-factor requirement, but also in optimum pH, kinetic characteristics, sensitivity to potential steroidal inhibitors and sensitivity to detergents, ionic strength and temperature. Moreover, salient sex differences exist in the activity of all three kidney enzymes. The soluble NADPH-dependent enzyme is more active in female rats whereas both microsomal enzymes are considerably more active in male animals. The microsomal NADH-dependent oxidoreductase displays favorable characteristics to catalyze the 3alpha-dehydrogenation of 3alpha-androstanediol. Evidence is presented that it is mainly this enzyme that enables the kidney to use 3alpha-androstanediol as an efficient precursor for the local formation of 5alpha-dihydrotestosterone."}
{"id": "PMID:7456", "title": "Influence of DNA acidification on DNA premelting and template properties.", "content": "Acidification of a T7 DNA sample was found to be partly irreversible as ultraviolet difference spectra measured at various sub-melting temperatures were different from those observed for a 'normal' DNA sample. This implies some subtle conformational change which is not reversed by return to neutral pH. In the same conditions, only poly(purine)-poly(pyrimidine) polymers behaved in a different manner, during premelting, according to whether they were previously acidified or not. The properties of acidified and reneutralized T7 DNA were also investigated for Escherichia coli RNA polymerase binding and transcription. An inhibition of RNA synthesis and chain initiation was observed. The results suggest that the binding of the enzyme is affected. RNA synthesized is specific but there is a decrease in the number and in the stability of the RNA-polymerase-DNA complexes.", "contents": "Influence of DNA acidification on DNA premelting and template properties. Acidification of a T7 DNA sample was found to be partly irreversible as ultraviolet difference spectra measured at various sub-melting temperatures were different from those observed for a 'normal' DNA sample. This implies some subtle conformational change which is not reversed by return to neutral pH. In the same conditions, only poly(purine)-poly(pyrimidine) polymers behaved in a different manner, during premelting, according to whether they were previously acidified or not. The properties of acidified and reneutralized T7 DNA were also investigated for Escherichia coli RNA polymerase binding and transcription. An inhibition of RNA synthesis and chain initiation was observed. The results suggest that the binding of the enzyme is affected. RNA synthesized is specific but there is a decrease in the number and in the stability of the RNA-polymerase-DNA complexes."}
{"id": "PMID:7457", "title": "Reconstitution of chemically synthesized ribooligonucleotides with naturally occurring tRNA fragments.", "content": "Chemically synthesized yeast tRNA terminal fragments were reconstituted with natural tRNA fragments which were obtained by partial digestion with RNase T1. The synthetic 3'-nonanucleotide (I) accepted alanine (3% with respect to the intact tRNA) when combined with a 4-fold excess of the natural 5'-quarter and the chemically synthesized hexanucleotide (II) stimulated the aminoacylation of the natural 3'-half molecule.", "contents": "Reconstitution of chemically synthesized ribooligonucleotides with naturally occurring tRNA fragments. Chemically synthesized yeast tRNA terminal fragments were reconstituted with natural tRNA fragments which were obtained by partial digestion with RNase T1. The synthetic 3'-nonanucleotide (I) accepted alanine (3% with respect to the intact tRNA) when combined with a 4-fold excess of the natural 5'-quarter and the chemically synthesized hexanucleotide (II) stimulated the aminoacylation of the natural 3'-half molecule."}
{"id": "PMID:7458", "title": "Glycosidases of molluscs. Purification and properties of alpha-L-fucosidase from Chamelea gallina L.", "content": "An alpha-L-fucosidase had been purified approximately 300-fold from the liver (hepatopancreas) of the marine mollusc Chamelea gallina L. (= Venus gallina L.). During the different steps of the purification procedure it was difficult to remove the contaminant N-acetylglucosaminidase activity; but, after electrofocusing, a final preparation free of this and other glycosidades present in the crude extract was obtained. The purified enzyme has a broad specificity; it hydrolyzes p-nitrophenyl alpha-L-fucoside and natural substrates such as oligosaccharides containing fucosidic residues with alpha 1--2, alpha 1--3 and alpha 1--4 linkages; also it hydrolyzes fucose-containing glycopeptides, such as thyroglobulin glycopeptide, and glycoproteins as procine submaxillary mucin (previously rendered free of sialic acid). The enzyme has a pH optimum of 5.2 +/- 0.2, with a Km of 7 X 10(-5) M using p-nitrophenyl L-fucoside as substrate. It is inhibited by Hg2+ and some sugars, and activated by CN-, Zn2+, Ca2+ and EDTA. It shows two peaks by isoelectric focusing (at 6.3 and 6.6). The molecular weight of the alpha-L-fucosidase by gel filtration was over 2000000.", "contents": "Glycosidases of molluscs. Purification and properties of alpha-L-fucosidase from Chamelea gallina L. An alpha-L-fucosidase had been purified approximately 300-fold from the liver (hepatopancreas) of the marine mollusc Chamelea gallina L. (= Venus gallina L.). During the different steps of the purification procedure it was difficult to remove the contaminant N-acetylglucosaminidase activity; but, after electrofocusing, a final preparation free of this and other glycosidades present in the crude extract was obtained. The purified enzyme has a broad specificity; it hydrolyzes p-nitrophenyl alpha-L-fucoside and natural substrates such as oligosaccharides containing fucosidic residues with alpha 1--2, alpha 1--3 and alpha 1--4 linkages; also it hydrolyzes fucose-containing glycopeptides, such as thyroglobulin glycopeptide, and glycoproteins as procine submaxillary mucin (previously rendered free of sialic acid). The enzyme has a pH optimum of 5.2 +/- 0.2, with a Km of 7 X 10(-5) M using p-nitrophenyl L-fucoside as substrate. It is inhibited by Hg2+ and some sugars, and activated by CN-, Zn2+, Ca2+ and EDTA. It shows two peaks by isoelectric focusing (at 6.3 and 6.6). The molecular weight of the alpha-L-fucosidase by gel filtration was over 2000000."}
{"id": "PMID:7459", "title": "Cerebral blood flow, cerebral metabolism and cerebrospinal fluid biochemistry in brain-injured patients after exposure to hyperbaric oxygen.", "content": "A series of head-injured patients, in coma, were treated with hyperbaric oxygen (OHP) at 2.5 atm. Cerebral blood flow (CBF), cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGL), and lactate (CMRL act), and various cerebrospinal fluid (CSF) parameters were measured before and 2 h after the treatment. Pre-OHP and post-OHP average values of arterial blood and CSF lactate, and CMRL act were higher than normal, while CBF, CMRO2 and CSF oxygen pressure (PO2) were lower. CBF tended to increase after OHP in some patients and to decrease in others. This discrepancy and the conflicting results of the literature can be tentatively explained in assuming that there is a different effect of OHP on normal brain circulation as compared to impaired brain circulation. Changes of cerebral metabolic rates were inconsistent and did not relate to changes of CBF, except with repeated studies of the same patient. A correlation was found between the variations of CMRGL and those of arterial blood and CSF glucose content. CSF PO2, CSF acid-base balance, and CSF lactate content did not vary, and arterial PO2 showed a consistent fall. In two patients who were neurologically improved after OHP exposure, the CBF and metabolic changes were not the same.", "contents": "Cerebral blood flow, cerebral metabolism and cerebrospinal fluid biochemistry in brain-injured patients after exposure to hyperbaric oxygen. A series of head-injured patients, in coma, were treated with hyperbaric oxygen (OHP) at 2.5 atm. Cerebral blood flow (CBF), cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGL), and lactate (CMRL act), and various cerebrospinal fluid (CSF) parameters were measured before and 2 h after the treatment. Pre-OHP and post-OHP average values of arterial blood and CSF lactate, and CMRL act were higher than normal, while CBF, CMRO2 and CSF oxygen pressure (PO2) were lower. CBF tended to increase after OHP in some patients and to decrease in others. This discrepancy and the conflicting results of the literature can be tentatively explained in assuming that there is a different effect of OHP on normal brain circulation as compared to impaired brain circulation. Changes of cerebral metabolic rates were inconsistent and did not relate to changes of CBF, except with repeated studies of the same patient. A correlation was found between the variations of CMRGL and those of arterial blood and CSF glucose content. CSF PO2, CSF acid-base balance, and CSF lactate content did not vary, and arterial PO2 showed a consistent fall. In two patients who were neurologically improved after OHP exposure, the CBF and metabolic changes were not the same."}
{"id": "PMID:7460", "title": "A new type of fluorocarbon liquid oxygenator.", "content": "A new oxygenator based on gas transfer across liquid-liquid interfaces (liquid oxygenator) is introduced. Perfluorinated chemicals are used as gas carriers. This liquid oxygenator differs from others in its concept basing on the dispersion of the blood droplets in an inert liquid by means of shear forces. This method allows high efficiency both with respect to saturation and to required blood flow. The results of gas transfer experiments in vitro and in vivo are satisfactory.", "contents": "A new type of fluorocarbon liquid oxygenator. A new oxygenator based on gas transfer across liquid-liquid interfaces (liquid oxygenator) is introduced. Perfluorinated chemicals are used as gas carriers. This liquid oxygenator differs from others in its concept basing on the dispersion of the blood droplets in an inert liquid by means of shear forces. This method allows high efficiency both with respect to saturation and to required blood flow. The results of gas transfer experiments in vitro and in vivo are satisfactory."}
{"id": "PMID:7461", "title": "A simplified bloodless procedure for extensive hepatectomy. Experimental study in the pig.", "content": "An original procedure of extensive bloodless hepatectomy is described in the pig. Complete vascular liver isolation with aorta clamping up to 25 min allows 60-75% bloodless hepatectomy without any portal triad dissection. Perfect hemostasis and shortening of liver ischemia is obtained with the use of a gelatin-resorcin-formaldehyde adhesive. Hemodynamic tolerance is good, and liver regeneration appears to be as fast as in minor species.", "contents": "A simplified bloodless procedure for extensive hepatectomy. Experimental study in the pig. An original procedure of extensive bloodless hepatectomy is described in the pig. Complete vascular liver isolation with aorta clamping up to 25 min allows 60-75% bloodless hepatectomy without any portal triad dissection. Perfect hemostasis and shortening of liver ischemia is obtained with the use of a gelatin-resorcin-formaldehyde adhesive. Hemodynamic tolerance is good, and liver regeneration appears to be as fast as in minor species."}
{"id": "PMID:7466", "title": "Purification and some properties of NADP+ -specific isocitrate dehydrogenase from an extreme thermophile, Thermus flavus AT-62.", "content": "Thermostable NADP+ -specific isocitrate dehydrogenase (EC 1.1.1.42) was purified from crude extract of an extremely thermophilic bacterium Thermus flavus AT-62 through DEAE-cellulose column, acetone fractionation, DEAE-Sephadex A-50 column and isoelectric focussing. The enzyme was purified about 500-folds in its specific activity and purity was found to be about 96%. The enzyme was not inactivated after 60 min at 70 degrees C, but 20 and 80% of the activity were lost after 60 min at 80 degrees and 90 degrees C, respectively. Oxalacetate plus glyoxylate (each 1 nM) demonstrated 75% inhibition of the activity in concerted manner. The degree of the inhibition and the affinity of the enzyme for isocitrate and NADP+ decreased with the rise of temperature, especially above 60 degrees C. The activation energy below and above 60 degrees C were 14,500 and 8,000 cal per mole respectively. In CD spectra negative bands at 210 and 220nm were observed and alpha-helix content was calculated to be about 26%. In the course of heating up to 60 degrees practically no change in CD bands are observed, but above 60 degrees the depth of CD bands decreased gradually and remarkably above 80 degrees C. The effect of temperature on kinetic parameters and secondary structures of the enzyme was discussed in relation to the temperature adaptation of the organism.", "contents": "Purification and some properties of NADP+ -specific isocitrate dehydrogenase from an extreme thermophile, Thermus flavus AT-62. Thermostable NADP+ -specific isocitrate dehydrogenase (EC 1.1.1.42) was purified from crude extract of an extremely thermophilic bacterium Thermus flavus AT-62 through DEAE-cellulose column, acetone fractionation, DEAE-Sephadex A-50 column and isoelectric focussing. The enzyme was purified about 500-folds in its specific activity and purity was found to be about 96%. The enzyme was not inactivated after 60 min at 70 degrees C, but 20 and 80% of the activity were lost after 60 min at 80 degrees and 90 degrees C, respectively. Oxalacetate plus glyoxylate (each 1 nM) demonstrated 75% inhibition of the activity in concerted manner. The degree of the inhibition and the affinity of the enzyme for isocitrate and NADP+ decreased with the rise of temperature, especially above 60 degrees C. The activation energy below and above 60 degrees C were 14,500 and 8,000 cal per mole respectively. In CD spectra negative bands at 210 and 220nm were observed and alpha-helix content was calculated to be about 26%. In the course of heating up to 60 degrees practically no change in CD bands are observed, but above 60 degrees the depth of CD bands decreased gradually and remarkably above 80 degrees C. The effect of temperature on kinetic parameters and secondary structures of the enzyme was discussed in relation to the temperature adaptation of the organism."}
{"id": "PMID:7467", "title": "Maintainance of specificity, information, and thermostability in thermophilic Bacillus sp. glutamine synthetase.", "content": "Glutamine synthetase has been purified to homogeneity from B. subtilis (37 degrees) B. stearothermophilus (55 degrees), and B. caldolyticus (75 degrees). Those characteristics compared include size (6.0 +/- 0.3 X 10(5) daltons), quaternary structure (12 SU) amino acid content, substrate Km's and specificity for structural analogs, metal ion activation, number and kind of separate feedback modifier sites, and the complexity of modifier-substrate and modifier-modifier site interactions. Although the 37 degrees and 55 degrees systems are quite similar, the 75 degrees system shows important alterations in substrate specificity and modes of modifier action. Whereas at 37 degrees and 55 degrees AMP inhibits synergistically with amino acids (glycine, glutamine, histidine), the 75 degrees enzyme is inhibited directly by the products ADP, (which assumes the role of AMP) and glutamine, plus other ligands. Ligand binding domains are compared and found to be very different. Thermostabilization occurs by (a) protection by bound L-glutamate, (b) protein aggregation, (c) trends in the content of total polar residues, total Asx + Flx residues, the average hydrophobicity, and (d) disulfide bond cross-linking. Such studies provide insights to molecular evolution occurring with changes in environmental stress.", "contents": "Maintainance of specificity, information, and thermostability in thermophilic Bacillus sp. glutamine synthetase. Glutamine synthetase has been purified to homogeneity from B. subtilis (37 degrees) B. stearothermophilus (55 degrees), and B. caldolyticus (75 degrees). Those characteristics compared include size (6.0 +/- 0.3 X 10(5) daltons), quaternary structure (12 SU) amino acid content, substrate Km's and specificity for structural analogs, metal ion activation, number and kind of separate feedback modifier sites, and the complexity of modifier-substrate and modifier-modifier site interactions. Although the 37 degrees and 55 degrees systems are quite similar, the 75 degrees system shows important alterations in substrate specificity and modes of modifier action. Whereas at 37 degrees and 55 degrees AMP inhibits synergistically with amino acids (glycine, glutamine, histidine), the 75 degrees enzyme is inhibited directly by the products ADP, (which assumes the role of AMP) and glutamine, plus other ligands. Ligand binding domains are compared and found to be very different. Thermostabilization occurs by (a) protection by bound L-glutamate, (b) protein aggregation, (c) trends in the content of total polar residues, total Asx + Flx residues, the average hydrophobicity, and (d) disulfide bond cross-linking. Such studies provide insights to molecular evolution occurring with changes in environmental stress."}
{"id": "PMID:7468", "title": "Properties of enzymes from Clostridium thermoaceticum and Clostridium formicoaceticum.", "content": "Methylenetetrahydrofolate dehydrogenase from C. thermoaceticum and C. formicoaceticum have been purified to homogeneity and compared. The two enzymes are very similar physically, chemically, and kinetically, but he C. thermoaceticum enzyme has a higher thermostablility, which is an intrinsic property of the protein. Formate dehydrogenase enzymes from both bacteria require selenite and tungstate for formation and these enzymes also appear to have similar properties, although the C. thermoaceticum is stable at 70 degrees C for more than one hour. Acetate kinase from C. thermoaceticum appears to be under metabolic  control. It can be concluded that enzymes from C. thermoaceticum, although they are more thermostable, are very similar to corresponding enzymes from mesophilic organisms.", "contents": "Properties of enzymes from Clostridium thermoaceticum and Clostridium formicoaceticum. Methylenetetrahydrofolate dehydrogenase from C. thermoaceticum and C. formicoaceticum have been purified to homogeneity and compared. The two enzymes are very similar physically, chemically, and kinetically, but he C. thermoaceticum enzyme has a higher thermostablility, which is an intrinsic property of the protein. Formate dehydrogenase enzymes from both bacteria require selenite and tungstate for formation and these enzymes also appear to have similar properties, although the C. thermoaceticum is stable at 70 degrees C for more than one hour. Acetate kinase from C. thermoaceticum appears to be under metabolic  control. It can be concluded that enzymes from C. thermoaceticum, although they are more thermostable, are very similar to corresponding enzymes from mesophilic organisms."}
{"id": "PMID:7470", "title": "Studies on the inhibition of thermolysin.", "content": "Thei nhibition of the thermolysin catalyzed hydrolysis of FA-Gly-Leu-NH2 and FA-Gly-Phe-NH2 has been reported. The results suggest a model for substrate and inhibitor binding involving the hydrophobic specificity pocket, Arg-203 and Glu-143.", "contents": "Studies on the inhibition of thermolysin. Thei nhibition of the thermolysin catalyzed hydrolysis of FA-Gly-Leu-NH2 and FA-Gly-Phe-NH2 has been reported. The results suggest a model for substrate and inhibitor binding involving the hydrophobic specificity pocket, Arg-203 and Glu-143."}
{"id": "PMID:7472", "title": "Muscle metabolism investigated at rest and during exercise and/or pharmacological treatment by vasodilators.", "content": "The Ruderman's preparation was utilized to investigate in situ some aspects of the muscular metabolism both at rest and during submaximal exercise upon bilateral sciatic nerve stimulation, and/or during perfusion with some vasodilators: papaverine, caffeine, nicergoline, bamethan. O2 and glucose uptake, the production of lactate and the glycogen level of the muscle were studied. The availability of acetoacetate modifies the muscular metabolism; other fuels (e.g. the ketone body itself) are probably used for energetic purposes both under basal conditions and during exercise, even in the presence of high glycogen concentrations in the tissues. Some vasodilators increase the utilization of other fuels in replacement of glycogen (e.g. nicergoline), some others increase the ulilization of glycogen itself (e.g. bamethan and caffeine), whereas others (e.g. papaverine) do not effect the biochemical parameters studied. The present data confirm the importance both of the substrate availability and of the power of drugs to interfere with some enzymatic systems which modulate the utilization of available substrates, especially during exercise.", "contents": "Muscle metabolism investigated at rest and during exercise and/or pharmacological treatment by vasodilators. The Ruderman's preparation was utilized to investigate in situ some aspects of the muscular metabolism both at rest and during submaximal exercise upon bilateral sciatic nerve stimulation, and/or during perfusion with some vasodilators: papaverine, caffeine, nicergoline, bamethan. O2 and glucose uptake, the production of lactate and the glycogen level of the muscle were studied. The availability of acetoacetate modifies the muscular metabolism; other fuels (e.g. the ketone body itself) are probably used for energetic purposes both under basal conditions and during exercise, even in the presence of high glycogen concentrations in the tissues. Some vasodilators increase the utilization of other fuels in replacement of glycogen (e.g. nicergoline), some others increase the ulilization of glycogen itself (e.g. bamethan and caffeine), whereas others (e.g. papaverine) do not effect the biochemical parameters studied. The present data confirm the importance both of the substrate availability and of the power of drugs to interfere with some enzymatic systems which modulate the utilization of available substrates, especially during exercise."}
{"id": "PMID:7473", "title": "Factors in the evolution of hemoglobin function.", "content": "The packaging of vertebrate blood hemoglobins within cells places subtle constraints on hemoglobin evolution. Since the concentration of hemoglobin is near the solubility limit a selective advantage should exist for a noncomplementary external topology of amino acid residues. Further, any change in charge on the protein should alter ion distribution across the cell membrane and so modify ion-sensitive oxygen transport. An efficient hemoglobin must not only combine readily with oxygen at prevailing environmental oxygen pressures, but must also release it at metabolically appropriate pressures. These adaptations frequently employ different strategies to achieve the same objective in different animals. Some hemoglobins have evolved special properties unrelated to the transport of oxygen to metabolizing tissues. Thus many teleost fish have hemoglobins that discharge much of their oxygen at low pH even at high oxygen pressures. This property appears to aid in filling the swim bladder with oxygen. The hemoglobins of elasmobranchs have evoked a unique resistance to urea as a consequence of the high urea content of their blood. Sometimes the functional adaptations of hemoglobins are achieved by multiple hemoglobins in the same cells. Often, however, different red cell populations with functionally unique hemoglobins arise sequentially during ontogeny.", "contents": "Factors in the evolution of hemoglobin function. The packaging of vertebrate blood hemoglobins within cells places subtle constraints on hemoglobin evolution. Since the concentration of hemoglobin is near the solubility limit a selective advantage should exist for a noncomplementary external topology of amino acid residues. Further, any change in charge on the protein should alter ion distribution across the cell membrane and so modify ion-sensitive oxygen transport. An efficient hemoglobin must not only combine readily with oxygen at prevailing environmental oxygen pressures, but must also release it at metabolically appropriate pressures. These adaptations frequently employ different strategies to achieve the same objective in different animals. Some hemoglobins have evolved special properties unrelated to the transport of oxygen to metabolizing tissues. Thus many teleost fish have hemoglobins that discharge much of their oxygen at low pH even at high oxygen pressures. This property appears to aid in filling the swim bladder with oxygen. The hemoglobins of elasmobranchs have evoked a unique resistance to urea as a consequence of the high urea content of their blood. Sometimes the functional adaptations of hemoglobins are achieved by multiple hemoglobins in the same cells. Often, however, different red cell populations with functionally unique hemoglobins arise sequentially during ontogeny."}
{"id": "PMID:7476", "title": "Testicular microlithiasis with sterility.", "content": "A case report of male infertility associated with testicular microlithiasis is presented. This rare condition has not previously been associated with infertility. A variable maturation arrest was observed in the spermatogenic epithelium. The question of whether the microliths are the cause of the infertility or whether both conditions are the result of some unknown agent must await further elucidation.", "contents": "Testicular microlithiasis with sterility. A case report of male infertility associated with testicular microlithiasis is presented. This rare condition has not previously been associated with infertility. A variable maturation arrest was observed in the spermatogenic epithelium. The question of whether the microliths are the cause of the infertility or whether both conditions are the result of some unknown agent must await further elucidation."}
{"id": "PMID:7477", "title": "Quantitative parameters for light microscopic assessment of the tubuli seminiferi.", "content": "For quantitative, histologic assessment of the testis tubuli there are four suitable parameters: diameter of tubulus, area of tubulus, number of cell nuclei per tubulus, and area of nuclei of the various cells participating in spermatogenesis. For estimating areas, the integrative method of measurement, either with a grid or with the aid of the manual optical picture-analysis system, is proposed. The tubulus diameter can be determined rapidly and easily, although the tubulus size can be assessed more accurately by area estimation. An assessment of reproductive capacity in detail is possible by means of rather time-consuming determination of cell nucleus number and nuclear area, whereby the stages of the cycle of the seminiferous epithelium must be considered.", "contents": "Quantitative parameters for light microscopic assessment of the tubuli seminiferi. For quantitative, histologic assessment of the testis tubuli there are four suitable parameters: diameter of tubulus, area of tubulus, number of cell nuclei per tubulus, and area of nuclei of the various cells participating in spermatogenesis. For estimating areas, the integrative method of measurement, either with a grid or with the aid of the manual optical picture-analysis system, is proposed. The tubulus diameter can be determined rapidly and easily, although the tubulus size can be assessed more accurately by area estimation. An assessment of reproductive capacity in detail is possible by means of rather time-consuming determination of cell nucleus number and nuclear area, whereby the stages of the cycle of the seminiferous epithelium must be considered."}
{"id": "PMID:7482", "title": "Influence of a meal on the absorption of cimetidine. A new histamine H2-receptor antagonist.", "content": "Absorption of an oral dose of 300 mg of Cimetidine was studied after an overnight fast in six healthy male volunteers on three separate occasions, 20 min before, during, and 2 h after a standard breakfast. Compared to the doses taken before and after the meal, the dose taken with the meal showed a significant delay in the time taken to reach therapeutic blood concentrations of the drug with no reduction in the period of time during which this concentration was maintained. We, therefore, suggest that the drug should be taken with a meal to achieve optimal acid inhibition in the interdigestive period.", "contents": "Influence of a meal on the absorption of cimetidine. A new histamine H2-receptor antagonist. Absorption of an oral dose of 300 mg of Cimetidine was studied after an overnight fast in six healthy male volunteers on three separate occasions, 20 min before, during, and 2 h after a standard breakfast. Compared to the doses taken before and after the meal, the dose taken with the meal showed a significant delay in the time taken to reach therapeutic blood concentrations of the drug with no reduction in the period of time during which this concentration was maintained. We, therefore, suggest that the drug should be taken with a meal to achieve optimal acid inhibition in the interdigestive period."}
{"id": "PMID:7517", "title": "Hemoglobin function in stored blood. XIII. A citrate-adenine preservative with optimal pH to maintain red cell 2,3-DPG (function) and ATP (viability).", "content": "Increasing pH by a 0.5 increment over the commonly used preservative, acid-citrate-dextrose with adenine (ACD-Ad), results in a significant improvement in 2,3-DPG, with no significant loss in concentrations of ATP. The intermediate pH preservative, 6.0, also had ATP concentrations which equaled those of the low pH preservatives, 5.0 and 5.5, from the 21st to the 42nd day of storage. A citrate-adenine preservative, with a pH between 5.5 and 6.0, would seem to be optimal for maintenance of hemoglobin function and red cell viability, as determined by measurements of 2,3-DPG and ATP concentrations.", "contents": "Hemoglobin function in stored blood. XIII. A citrate-adenine preservative with optimal pH to maintain red cell 2,3-DPG (function) and ATP (viability). Increasing pH by a 0.5 increment over the commonly used preservative, acid-citrate-dextrose with adenine (ACD-Ad), results in a significant improvement in 2,3-DPG, with no significant loss in concentrations of ATP. The intermediate pH preservative, 6.0, also had ATP concentrations which equaled those of the low pH preservatives, 5.0 and 5.5, from the 21st to the 42nd day of storage. A citrate-adenine preservative, with a pH between 5.5 and 6.0, would seem to be optimal for maintenance of hemoglobin function and red cell viability, as determined by measurements of 2,3-DPG and ATP concentrations."}
{"id": "PMID:7519", "title": "[Studies on biosynthesis of short-chain fatty acids (author's transl)].", "content": "Studies were reported here on biosynthesis of short-chain fatty acids in lactating rabbit mammary glands. The maximal incorporation from [1-14C] acetate into total fatty acids were observed in microsomes and supernatant fractions of mammary glands but the synthetic rate either in the microsomes alone or in the supernatant alone was rather low. However approximately 80% of the maximal rate was restored in the supernatant for n-butyric acid synthesis. The incorporation from [1-14C] acetate into-n-butyric acid was markedly stimulated in the presence of NADH, compared to NADPH while total fatty acids synthesis was more dependent on NADPH. Long-chain fatty acids synthesis from [1-14C] acetate was decreased markedly by the addition of avidin although n-butyric acid formation was restored to 80%. Then by the addition of malonyl CoA or biotin the avidin system, middle- and long-chain fatty acids were recovered again. [1-14C] propionate was incorporated into even-numbered chain fatty acids as well as odd chain fatty acids. The synthesis of total fatty acids from [1-14C] propionate was more dependent on NADPH-generating system than either NADH or NADPH. [1-14C] bicarbonate was also incorporated slightly into fatty acids, such as decanoic or dodecanoic acids. In the reduction from either acetoacetyl CoA or crotonyl CoA, the tritium of NADP3H was stereospecifically incorporated into the beta-position of n-butyric acid. The reaction of acetoacetyl CoA reduction was much more dependent on NADH while crotonyl CoA was more reduced with NADPH. There was no difference between the dependencies on NADH and NADPH in the reduction of 2-hexenyl CoA.", "contents": "[Studies on biosynthesis of short-chain fatty acids (author's transl)]. Studies were reported here on biosynthesis of short-chain fatty acids in lactating rabbit mammary glands. The maximal incorporation from [1-14C] acetate into total fatty acids were observed in microsomes and supernatant fractions of mammary glands but the synthetic rate either in the microsomes alone or in the supernatant alone was rather low. However approximately 80% of the maximal rate was restored in the supernatant for n-butyric acid synthesis. The incorporation from [1-14C] acetate into-n-butyric acid was markedly stimulated in the presence of NADH, compared to NADPH while total fatty acids synthesis was more dependent on NADPH. Long-chain fatty acids synthesis from [1-14C] acetate was decreased markedly by the addition of avidin although n-butyric acid formation was restored to 80%. Then by the addition of malonyl CoA or biotin the avidin system, middle- and long-chain fatty acids were recovered again. [1-14C] propionate was incorporated into even-numbered chain fatty acids as well as odd chain fatty acids. The synthesis of total fatty acids from [1-14C] propionate was more dependent on NADPH-generating system than either NADH or NADPH. [1-14C] bicarbonate was also incorporated slightly into fatty acids, such as decanoic or dodecanoic acids. In the reduction from either acetoacetyl CoA or crotonyl CoA, the tritium of NADP3H was stereospecifically incorporated into the beta-position of n-butyric acid. The reaction of acetoacetyl CoA reduction was much more dependent on NADH while crotonyl CoA was more reduced with NADPH. There was no difference between the dependencies on NADH and NADPH in the reduction of 2-hexenyl CoA."}
{"id": "PMID:7520", "title": "An analysis of the relationships among obesity, plasma insulin and hepatic lipogenic enzymes in \"viable yellow obese\" mice (Avy/a).", "content": "The development of obesity, hyperinsulinemia and six hepatic lipogenic enzymes in Avy/a mice were compared to that in a/a mice. Correlation between body weight, liver weight, plasma insulin concentration and activities of hepatic enzymes was analyzed. In the Avy/a mice, body weight, liver weight and plasma insulin level increased steadily as the mice aged. In the a/a mice, the change of these three parameters was much slower. Plasma insulin concentration in a/a mice did not increase until eight months of age. Compared with a/a mice, Avy/a mice had higher 6-phosphogluconate dehydrogenase and fatty acid synthetase activities at two months of age; lower citrate cleavage enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities at three months of age; lower citrate cleavage enzyme and glucose-6-phosphate dehydrogenase and higher acetyl CoA carboxylase activities at five months of age; and higher malic enzyme, citrate cleavage enzyme and 6-phosphogluconate dehydrogenase activities at eight months of age. There were significant correlations between plasma insulin level and body weight and between plasma insulin level and the activities of malic enzyme and citrate cleavage enzyme in Avy/a mice. The correlation between body weight and malic enzyme and citrate cleavage enzyme activities disappeared after the analysis was adjusted for plasma insulin level.", "contents": "An analysis of the relationships among obesity, plasma insulin and hepatic lipogenic enzymes in \"viable yellow obese\" mice (Avy/a). The development of obesity, hyperinsulinemia and six hepatic lipogenic enzymes in Avy/a mice were compared to that in a/a mice. Correlation between body weight, liver weight, plasma insulin concentration and activities of hepatic enzymes was analyzed. In the Avy/a mice, body weight, liver weight and plasma insulin level increased steadily as the mice aged. In the a/a mice, the change of these three parameters was much slower. Plasma insulin concentration in a/a mice did not increase until eight months of age. Compared with a/a mice, Avy/a mice had higher 6-phosphogluconate dehydrogenase and fatty acid synthetase activities at two months of age; lower citrate cleavage enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities at three months of age; lower citrate cleavage enzyme and glucose-6-phosphate dehydrogenase and higher acetyl CoA carboxylase activities at five months of age; and higher malic enzyme, citrate cleavage enzyme and 6-phosphogluconate dehydrogenase activities at eight months of age. There were significant correlations between plasma insulin level and body weight and between plasma insulin level and the activities of malic enzyme and citrate cleavage enzyme in Avy/a mice. The correlation between body weight and malic enzyme and citrate cleavage enzyme activities disappeared after the analysis was adjusted for plasma insulin level."}
{"id": "PMID:7532", "title": "Studies on normal human bone marrow cultures in controlled environment thin-film culture systems.", "content": "Two thin film culture systems, the controlled environment steady state system (SS) and the rocker tube configuration of that system (RT), were used to identify some of the conditions that appear to maintain morphologic and functional characteristics of cells of human bone marrow explants in vitro. The systems configuration assured continual gassing, control and easy monitoring of the cultures. Cytocentrifuge preparations of media of specimens cultured in RT disclosed, though in decreasing numbers, various hematopoietic cells for periods exceeding one month. Hematopoietic cells shed from specimens cultured in the SS system were retained in the culture tubes; cells of the myelocytic series predominated for the first two weeks while an increasing number of monocytes and macrophages appeared in the media of of older cultures. Histologic examination of cultured explants disclosed preservation of the marrow architecture and the persistence of hematopoietic cells. Specimens cultured in RT tubes tended to be less cellular than similar cultures placed in dialysis bags or as cultured in the SS system. Immunoglobulins (Ig) were released into the culture media at a constant rate throughout the period of culture. Specimens that were cultured at a controlled pH of 7.4 released 2 to more than 4 times as much Ig as similar specimens maintained at a pH level of 7.1. There were no definitive differences in Ig levels in the cultures maintained at comparable pH levels and overlaid with various CO2 concentrations, i.e. 2%, 5%, 10% similarly, no differences in Ig levels were found in specimens cultured in media containing fetal bovine sera as opposed to horse sera.", "contents": "Studies on normal human bone marrow cultures in controlled environment thin-film culture systems. Two thin film culture systems, the controlled environment steady state system (SS) and the rocker tube configuration of that system (RT), were used to identify some of the conditions that appear to maintain morphologic and functional characteristics of cells of human bone marrow explants in vitro. The systems configuration assured continual gassing, control and easy monitoring of the cultures. Cytocentrifuge preparations of media of specimens cultured in RT disclosed, though in decreasing numbers, various hematopoietic cells for periods exceeding one month. Hematopoietic cells shed from specimens cultured in the SS system were retained in the culture tubes; cells of the myelocytic series predominated for the first two weeks while an increasing number of monocytes and macrophages appeared in the media of of older cultures. Histologic examination of cultured explants disclosed preservation of the marrow architecture and the persistence of hematopoietic cells. Specimens cultured in RT tubes tended to be less cellular than similar cultures placed in dialysis bags or as cultured in the SS system. Immunoglobulins (Ig) were released into the culture media at a constant rate throughout the period of culture. Specimens that were cultured at a controlled pH of 7.4 released 2 to more than 4 times as much Ig as similar specimens maintained at a pH level of 7.1. There were no definitive differences in Ig levels in the cultures maintained at comparable pH levels and overlaid with various CO2 concentrations, i.e. 2%, 5%, 10% similarly, no differences in Ig levels were found in specimens cultured in media containing fetal bovine sera as opposed to horse sera."}
{"id": "PMID:7533", "title": "Bactericidal mechanisms in rabbit alveolar macrophages: evidence against peroxidase and hydrogen peroxide bactericidal mechanisms.", "content": "The role of peroxidase-mediated bacterial killing by rabbit alveolar macrophages was examined. During 3 h of incubation in vitro, alveolar macrophages ingested and killed greater than 88% of the Streptococcus faecalis, Proteus mirabilis, or Streptococcus pneumoniae present in the incubation mixture. Preincubation of alveolar macrophages with inhibitors of catalase, 3-amino-1,2,4-triazole or sodium nitrite, did not alter their bactericidal potential. Iodination of ingested zymosan particles, a peroxidase-dependent and hydrogen peroxide-dependent reaction, was not observed, in spite of vigorous phagocytosis by alveolar macrophages. Furthermore, iodination by alveolar macrophages was not significantly increased when peroxidase-coated zymosan particles were ingested. The results suggest that hydrogen peroxide may not be available to the phagocytic vacuole for microbial killing. Since tetrazolium dye reduction reflects the activity of an oxidase responsible for stimulated oxygen consumption by polymorphonuclear leukocytes, this reaction was also measured. Rabbit alveolar macrophages incubated with latex particles did not exhibit an increased dye reduction compared with resting cells. The absence of significant stimulation of tetrazolium dye reduction indicates that the oxidase reaction does not occur in the proximity of the phagocytic vacuole of alveolar macrophages.", "contents": "Bactericidal mechanisms in rabbit alveolar macrophages: evidence against peroxidase and hydrogen peroxide bactericidal mechanisms. The role of peroxidase-mediated bacterial killing by rabbit alveolar macrophages was examined. During 3 h of incubation in vitro, alveolar macrophages ingested and killed greater than 88% of the Streptococcus faecalis, Proteus mirabilis, or Streptococcus pneumoniae present in the incubation mixture. Preincubation of alveolar macrophages with inhibitors of catalase, 3-amino-1,2,4-triazole or sodium nitrite, did not alter their bactericidal potential. Iodination of ingested zymosan particles, a peroxidase-dependent and hydrogen peroxide-dependent reaction, was not observed, in spite of vigorous phagocytosis by alveolar macrophages. Furthermore, iodination by alveolar macrophages was not significantly increased when peroxidase-coated zymosan particles were ingested. The results suggest that hydrogen peroxide may not be available to the phagocytic vacuole for microbial killing. Since tetrazolium dye reduction reflects the activity of an oxidase responsible for stimulated oxygen consumption by polymorphonuclear leukocytes, this reaction was also measured. Rabbit alveolar macrophages incubated with latex particles did not exhibit an increased dye reduction compared with resting cells. The absence of significant stimulation of tetrazolium dye reduction indicates that the oxidase reaction does not occur in the proximity of the phagocytic vacuole of alveolar macrophages."}
{"id": "PMID:7534", "title": "Interactions between aminoglycoside antibiotics and carbenicillin or ticarillin.", "content": "Carbenicillin or ticarcillin were incubated individually with each of the following antibiotics: gentamicin, tobramycin, sisomicin, amikacin. The residual activity of each aminoglycoside in this mixture was assayed enzymatically. Amikacin was inactivated the least of the aminoglycosides. Both penicillins inactivated each aminoglycoside to a similar extent by a degree which varied according to the medium of incubaiton, the least inactivation being seen in pooled human serum and the most in phosphate buffer at pH 7.4.", "contents": "Interactions between aminoglycoside antibiotics and carbenicillin or ticarillin. Carbenicillin or ticarcillin were incubated individually with each of the following antibiotics: gentamicin, tobramycin, sisomicin, amikacin. The residual activity of each aminoglycoside in this mixture was assayed enzymatically. Amikacin was inactivated the least of the aminoglycosides. Both penicillins inactivated each aminoglycoside to a similar extent by a degree which varied according to the medium of incubaiton, the least inactivation being seen in pooled human serum and the most in phosphate buffer at pH 7.4."}
{"id": "PMID:7535", "title": "Effects of beta-adrenergic stimulation on bone-marrow function in normal and sublethally irradiated mice. I. The effect of isoproterenol on cAMP content in bone-marrow cells in vivo and in vitro.", "content": "The effect of isoproterenol (IPR) on bone-marrow cAMP content was investigated in vivo and in vitro. In unirradiated CFW mice, the bone-marrow cAMP content was found to be elevated by the administration of noradrenaline, adrenaline and isoproterenol. After IPR administration, the increase in cAMP was biphasic with maxima at 1 and 15 min. An increase in cAMP content was also noted in bone-marrow of sublethally-irradiated mice, but no further increase was observed 15 min after the administration of IPR. Elevation of cAMP by either IPR or radiation was prevented by pretreatment with the beta-adrenergic blocking agent--propranolol. IPR was also effective in increasing the cAMP content when added to suspension of bone-marrow cells. This effect was abolished by propranolol. IPR did not increase cAMP levels in bone-marrow cells isolated from irradiated animals. The results suggest that the differentiated bone-marrow cells have beta-adrenergic receptors.", "contents": "Effects of beta-adrenergic stimulation on bone-marrow function in normal and sublethally irradiated mice. I. The effect of isoproterenol on cAMP content in bone-marrow cells in vivo and in vitro. The effect of isoproterenol (IPR) on bone-marrow cAMP content was investigated in vivo and in vitro. In unirradiated CFW mice, the bone-marrow cAMP content was found to be elevated by the administration of noradrenaline, adrenaline and isoproterenol. After IPR administration, the increase in cAMP was biphasic with maxima at 1 and 15 min. An increase in cAMP content was also noted in bone-marrow of sublethally-irradiated mice, but no further increase was observed 15 min after the administration of IPR. Elevation of cAMP by either IPR or radiation was prevented by pretreatment with the beta-adrenergic blocking agent--propranolol. IPR was also effective in increasing the cAMP content when added to suspension of bone-marrow cells. This effect was abolished by propranolol. IPR did not increase cAMP levels in bone-marrow cells isolated from irradiated animals. The results suggest that the differentiated bone-marrow cells have beta-adrenergic receptors."}
{"id": "PMID:7537", "title": "Lorazepam and diazepam in anxious outpatients. A controlled study.", "content": "The response of 134 anxious neurotic outpatients to lorazepam, diazepam, and placebo was assessed in a 4-week double-blind trial. Both active drugs produced significantly more symptom reduction than placebo. Lorazepam, however, proved effective primarily in those patients who did not complain of sedation, and produced greatest improvement in initially sicker patients. Sedation was significantly more disturbing to lorazepam-treated patients than to diazepam-treated patients. Present findings suggested that 3 mg/day of lorazepam may be too high a dosage for mildly anxious patients, while 15 mg/day of diazepam seems an appropriate dosage for mildly anxious patients but may be too low a dosage for highly anxious patients.", "contents": "Lorazepam and diazepam in anxious outpatients. A controlled study. The response of 134 anxious neurotic outpatients to lorazepam, diazepam, and placebo was assessed in a 4-week double-blind trial. Both active drugs produced significantly more symptom reduction than placebo. Lorazepam, however, proved effective primarily in those patients who did not complain of sedation, and produced greatest improvement in initially sicker patients. Sedation was significantly more disturbing to lorazepam-treated patients than to diazepam-treated patients. Present findings suggested that 3 mg/day of lorazepam may be too high a dosage for mildly anxious patients, while 15 mg/day of diazepam seems an appropriate dosage for mildly anxious patients but may be too low a dosage for highly anxious patients."}
{"id": "PMID:7542", "title": "Collaborative study of a spectrofluorometric assay for Rauwolfia serpentina tablets and powdered root.", "content": "Reserpine-rescinnamine group alkaloids are extracted from Rauwolfia serpentina preparations into a dimethylsulfoxide (DMSO)-methanol mixture and diluted with 0.5N H2SO4. The chloroform extract of this solution is passed through a 0.1N NaOH-Celite column and then through a silica gel column. The weakly basic alkaloids trapped on the latter column are eluted with a methanol mixture; a portion of the eluate is treated with nitrous acid and the reserpine-rescinnamine content is determined by measuring the intensity of fluorescence of the oxidation product. The following means and standard deviations (11 collaborators) were obtained for the determination of reserpine-rescinnamine group alkaloids in 4 samples of Rauwolfia serpentina (NF reference powder, 100 mg and 50 mg commercial tablets, and a 45 mg synthetic tablet formulation) : 0.174% +/- 0.0112, 0.131% +/- 0.0047, 0.160% +/- 0.0100, and 0.153% +/- 0.0083, respectively.", "contents": "Collaborative study of a spectrofluorometric assay for Rauwolfia serpentina tablets and powdered root. Reserpine-rescinnamine group alkaloids are extracted from Rauwolfia serpentina preparations into a dimethylsulfoxide (DMSO)-methanol mixture and diluted with 0.5N H2SO4. The chloroform extract of this solution is passed through a 0.1N NaOH-Celite column and then through a silica gel column. The weakly basic alkaloids trapped on the latter column are eluted with a methanol mixture; a portion of the eluate is treated with nitrous acid and the reserpine-rescinnamine content is determined by measuring the intensity of fluorescence of the oxidation product. The following means and standard deviations (11 collaborators) were obtained for the determination of reserpine-rescinnamine group alkaloids in 4 samples of Rauwolfia serpentina (NF reference powder, 100 mg and 50 mg commercial tablets, and a 45 mg synthetic tablet formulation) : 0.174% +/- 0.0112, 0.131% +/- 0.0047, 0.160% +/- 0.0100, and 0.153% +/- 0.0083, respectively."}
{"id": "PMID:7543", "title": "Iron uptake in colicin B-resistant mutants of Escherichia coli K-12.", "content": "Four classes of colicin B-resistant mutants of Escherichia coli K-12 were examined for defects in iron uptake. All four mutant classes (cbt, exbC, exbB, and tonB) were defective in the uptake of ferri-ennterochelin. The tonB mutant was also defective in citrate-, ferrichrome-, and rhodoturulic acid-mediated iron uptake. The defects in iron transport were reflected in increased sensitivity to iron chelators and to chromium and aluminium salts, and in hypersecretion of enterochelin. One of the mutants (cbt) was apparently defective in outer membrane ferri-enterochelin receptor activity. aroE derivatives (unable to synthesize enterochelin) of the four mutant classes and the parent strain produced increased amounts of two outer membranes polypeptides when grown under iron stress. These polypeptides are implicated in ferri-enterochelin receptor activity.", "contents": "Iron uptake in colicin B-resistant mutants of Escherichia coli K-12. Four classes of colicin B-resistant mutants of Escherichia coli K-12 were examined for defects in iron uptake. All four mutant classes (cbt, exbC, exbB, and tonB) were defective in the uptake of ferri-ennterochelin. The tonB mutant was also defective in citrate-, ferrichrome-, and rhodoturulic acid-mediated iron uptake. The defects in iron transport were reflected in increased sensitivity to iron chelators and to chromium and aluminium salts, and in hypersecretion of enterochelin. One of the mutants (cbt) was apparently defective in outer membrane ferri-enterochelin receptor activity. aroE derivatives (unable to synthesize enterochelin) of the four mutant classes and the parent strain produced increased amounts of two outer membranes polypeptides when grown under iron stress. These polypeptides are implicated in ferri-enterochelin receptor activity."}
{"id": "PMID:7544", "title": "Calcium-requiring step in the uptake of deoxyribonucleic acid molecules through the surface of competent pneumococci.", "content": "The conversion of surface-adsorbed deoxyribonucleic acid (DNA) molecules to a state in which they are inaccessible to exogenous deoxyribonuclease requires specifically calcium ions; magnesium ions cannot replace calcium ions. Virtually maximal levels of nuclease-resistant DNA binding and genetic transformation can be obtained in media free from magnesium and containing only calcium ions. It is suggested that the calcium-requiring process is the transport of DNA molecules across the plasma membrane. Magnesium ions stimulate both the loss of surface-adsorbed DNA to the medium and the extracellular degradation of DNA.", "contents": "Calcium-requiring step in the uptake of deoxyribonucleic acid molecules through the surface of competent pneumococci. The conversion of surface-adsorbed deoxyribonucleic acid (DNA) molecules to a state in which they are inaccessible to exogenous deoxyribonuclease requires specifically calcium ions; magnesium ions cannot replace calcium ions. Virtually maximal levels of nuclease-resistant DNA binding and genetic transformation can be obtained in media free from magnesium and containing only calcium ions. It is suggested that the calcium-requiring process is the transport of DNA molecules across the plasma membrane. Magnesium ions stimulate both the loss of surface-adsorbed DNA to the medium and the extracellular degradation of DNA."}
{"id": "PMID:7545", "title": "Mechanism of autolysis of Neisseria gonorrhoeae.", "content": "The major autolysin(s) of Neisseria gonorrhoeae was solubilized from envelopes by extraction with 2% Triton X-100 containing 0.5 M NaCl. Neither Triton X-100 nor NaCl alone could effectively release the autolysin(s). The major autolysin is N-acetylmuramyl-L-alanine amidase (EC 3.5.1.28). The pH optimum for this reaction was broad, ranging from 5.5 to 8.5. Optimal hydrolysis of peptidoglycan occurred in 2% Triton X-100 in 0.1 M KCl. Attempts to purify the autolysin were unsuccessful. A rapid assay for enzyme activity was developed using radioactive cell walls as a substrate ([3H]diaminopimelic acid).", "contents": "Mechanism of autolysis of Neisseria gonorrhoeae. The major autolysin(s) of Neisseria gonorrhoeae was solubilized from envelopes by extraction with 2% Triton X-100 containing 0.5 M NaCl. Neither Triton X-100 nor NaCl alone could effectively release the autolysin(s). The major autolysin is N-acetylmuramyl-L-alanine amidase (EC 3.5.1.28). The pH optimum for this reaction was broad, ranging from 5.5 to 8.5. Optimal hydrolysis of peptidoglycan occurred in 2% Triton X-100 in 0.1 M KCl. Attempts to purify the autolysin were unsuccessful. A rapid assay for enzyme activity was developed using radioactive cell walls as a substrate ([3H]diaminopimelic acid)."}
{"id": "PMID:7546", "title": "Magnitude of the protonmotive force in respiring Staphylococcus aureus and Escherichia coli.", "content": "The membrane potential and pH gradient developed across the plasma membranes of whole cells of Staphylococcus aureus and spheroplasts of Escherichia coli were estimated. The distributions of potassium ions in the presence of valinomycin and the pH gradient across the membrane were determined from the changes in pK and pH observed in the external medium during transition from the energized respiring state to the de-engerized resting condition. The protonmotive force in respiring cells was estimated at 211 mV for S. aureus and 230 mV for E. coli at external pH values of approximately 6.5. The adequacy of these protonmotive forces as a driving force for substrate accumulation or adenosine 5'-triphosphate synthesis is discussed.", "contents": "Magnitude of the protonmotive force in respiring Staphylococcus aureus and Escherichia coli. The membrane potential and pH gradient developed across the plasma membranes of whole cells of Staphylococcus aureus and spheroplasts of Escherichia coli were estimated. The distributions of potassium ions in the presence of valinomycin and the pH gradient across the membrane were determined from the changes in pK and pH observed in the external medium during transition from the energized respiring state to the de-engerized resting condition. The protonmotive force in respiring cells was estimated at 211 mV for S. aureus and 230 mV for E. coli at external pH values of approximately 6.5. The adequacy of these protonmotive forces as a driving force for substrate accumulation or adenosine 5'-triphosphate synthesis is discussed."}
{"id": "PMID:7547", "title": "Proton movements coupled to lactate and alanine transport in Escherichia coli: isolation of mutants with altered stoichiometry in alanine transport.", "content": "The addition of lactate to lightly buffered suspensions of resting cells of Escherichia coli caused an increase in the pH of the extracellular phase as lactate and protons entered the cell together. From the magnitude of the pH change and the non-electrogenic character of lactate uptake, we concluded that the stoichiometry of the process was 1 proton/lactate anion. The addition of alanine caused a slow increase in pH, also apparently due to the transport of the amino acid by a symport mechanism with 1 proton/alanine stoichiometry. When cells were grown in the chemostat with alanine as sole carbon source and as limiting nutrient, this stoichiometry was found to alter to 2 protons/alanine, and then to 4 protons/alanine. These increases stoichiometries were due to the selection of mutants. The consequences of these changes on the potential uptake capacity of the cells are discussed.", "contents": "Proton movements coupled to lactate and alanine transport in Escherichia coli: isolation of mutants with altered stoichiometry in alanine transport. The addition of lactate to lightly buffered suspensions of resting cells of Escherichia coli caused an increase in the pH of the extracellular phase as lactate and protons entered the cell together. From the magnitude of the pH change and the non-electrogenic character of lactate uptake, we concluded that the stoichiometry of the process was 1 proton/lactate anion. The addition of alanine caused a slow increase in pH, also apparently due to the transport of the amino acid by a symport mechanism with 1 proton/alanine stoichiometry. When cells were grown in the chemostat with alanine as sole carbon source and as limiting nutrient, this stoichiometry was found to alter to 2 protons/alanine, and then to 4 protons/alanine. These increases stoichiometries were due to the selection of mutants. The consequences of these changes on the potential uptake capacity of the cells are discussed."}
{"id": "PMID:7548", "title": "Role of L-threonine dehydrogenase in the catabolism of threonine and synthesis of glycine by Escherichia coli.", "content": "The enzyme L-threonine dehydrogenase was demonstrated in extracts of Escherichia coli K-12, and was shown to be the first enzyme of the pathway converting threonine to glycine. The enzyme was induced by L-leucine, but not by its substrate, L-threonine. The metabolic significance of leucine as a catabolic signal for amino acid degradation is considered.", "contents": "Role of L-threonine dehydrogenase in the catabolism of threonine and synthesis of glycine by Escherichia coli. The enzyme L-threonine dehydrogenase was demonstrated in extracts of Escherichia coli K-12, and was shown to be the first enzyme of the pathway converting threonine to glycine. The enzyme was induced by L-leucine, but not by its substrate, L-threonine. The metabolic significance of leucine as a catabolic signal for amino acid degradation is considered."}
{"id": "PMID:7549", "title": "Partial characterization of a temperature-sensitive mutation affecting acetyl coenzyme A carboxylase in Escherichia coli K-12.", "content": "A temperature-sensitive mutation in Escherichia coli K-12 was shown to affect acetyl coenzyme A carboxylase and to map at min 63. This site is designated fabE.", "contents": "Partial characterization of a temperature-sensitive mutation affecting acetyl coenzyme A carboxylase in Escherichia coli K-12. A temperature-sensitive mutation in Escherichia coli K-12 was shown to affect acetyl coenzyme A carboxylase and to map at min 63. This site is designated fabE."}
{"id": "PMID:7550", "title": "Potentiometric studies on benzeneboronic acid-alpha-chymotrypsin interactions.", "content": "When the competitive inhibitor benzeneboronic acid (BBA) forms a complex with alpha-chymotrypsin [EC 3.4.21.1] protons are released in the acidic pH region. The proton release can be measured by a difference potentiometric technique. The proton release is also observed in chymotrypsinogen A but not in TRCK-, DIP-, and anhydrochymotrypsins. Based on these observations, a simple procedure to estimate the equilibrium constants of the trigonal-tetrahedral interconversion of BBA is proposed. Thermodynamic parameters of the ionization of His 57 and of each step involved in BBA binding can be estimated from the temperature dependence of the proton release. Those of His 57 are essentially the same as those of imidazole in water. Regarding the interconversion of BBA on the enzyme, the value of delta S is similar to delta S not equal to of the deacylation step of nonspecific substrates, and delta H is remarkably reduced from that for the ionization of BBA in water. The enthalpic gain of enzymic process is suggested to be due to the change of the proton acceptor, which is water in the case of the ionization of BBA in water, to imidazole on the enzyme.", "contents": "Potentiometric studies on benzeneboronic acid-alpha-chymotrypsin interactions. When the competitive inhibitor benzeneboronic acid (BBA) forms a complex with alpha-chymotrypsin [EC 3.4.21.1] protons are released in the acidic pH region. The proton release can be measured by a difference potentiometric technique. The proton release is also observed in chymotrypsinogen A but not in TRCK-, DIP-, and anhydrochymotrypsins. Based on these observations, a simple procedure to estimate the equilibrium constants of the trigonal-tetrahedral interconversion of BBA is proposed. Thermodynamic parameters of the ionization of His 57 and of each step involved in BBA binding can be estimated from the temperature dependence of the proton release. Those of His 57 are essentially the same as those of imidazole in water. Regarding the interconversion of BBA on the enzyme, the value of delta S is similar to delta S not equal to of the deacylation step of nonspecific substrates, and delta H is remarkably reduced from that for the ionization of BBA in water. The enthalpic gain of enzymic process is suggested to be due to the change of the proton acceptor, which is water in the case of the ionization of BBA in water, to imidazole on the enzyme."}
{"id": "PMID:7551", "title": "The removal of non-collagen components from newborn calf dermis with magnesium chloride solution.", "content": "1. Non-collagenous substances in newborn calf dermis were extracted with solutions of various concentrations of MgCl2. The total protein and hydroxyproline contents in MgCl2 extracts increased with increase in the concentration of MgCl2 in the solutions. In particular, steep increases of their contents were observed at concentrations of MgCl2 from 0.5 to 1.0 M. Total amounts of hydroxyproline in 1.0, 2.0, and 3.0 M MgCl2 extracts were equivalent to 40-50% of the hydroxyproline content in the whole connective tissue. Hexose and hexosamine contents of MgCl2 extracts increased with increase of the MgCl2 concentration. Hexuronic acid was hardly present in the residues after extractions with 0.5, 1.0, 2.0, and 3.0 M MgCl2. 2. Plasma proteins, hyaluronic acid, and dermatan sulfate were extracted at low concentrations of MgCl2. A non-collagenous protein and MgCl2-soluble collagen were extracted with 1.0, 2.0, and 3.0 M MgCl2 solutions. The disperson of collagen fibrils was observed in the residue extracted with 1.0 M MgCl2 solution by electron microscopy; the fibril structure of collagen was disordered by extraction with 2.0 and 3.0 M MgCl2. The results suggest that the dispersion and disorder of collagen fibrils lead to the release of a non-collagenous protein. Furthermore, it is suggested that the removal of hyaluronic acid and dermatan sulfate was not very effective for the solubilization of a large amount of collagen, but was suitable as a pretreatment to the extraction of a non-collagenous protein accompanied by the solubilization of a large amount of collagen. 3. The non-collagenous protein was purified by DEAE-cellulose column chromatography. Polyacrylamide gel electrophoresis of this protein at pH 8.5 showed a single band moving to the cathode. The non-collagenous protein contained 3.7% hexose, 1.8% hexosamine, and no hexuronic acid. This protein is rich in glycine, glutamic acid, and alanine, and contains neither hydroxyproline nor hydroxylysine. Sedimentation analysis showed a single peak with 1.8 S and the molecular weight was approx. 43,000 as determided by SDS polyacrylamide gel electrophoresis.", "contents": "The removal of non-collagen components from newborn calf dermis with magnesium chloride solution. 1. Non-collagenous substances in newborn calf dermis were extracted with solutions of various concentrations of MgCl2. The total protein and hydroxyproline contents in MgCl2 extracts increased with increase in the concentration of MgCl2 in the solutions. In particular, steep increases of their contents were observed at concentrations of MgCl2 from 0.5 to 1.0 M. Total amounts of hydroxyproline in 1.0, 2.0, and 3.0 M MgCl2 extracts were equivalent to 40-50% of the hydroxyproline content in the whole connective tissue. Hexose and hexosamine contents of MgCl2 extracts increased with increase of the MgCl2 concentration. Hexuronic acid was hardly present in the residues after extractions with 0.5, 1.0, 2.0, and 3.0 M MgCl2. 2. Plasma proteins, hyaluronic acid, and dermatan sulfate were extracted at low concentrations of MgCl2. A non-collagenous protein and MgCl2-soluble collagen were extracted with 1.0, 2.0, and 3.0 M MgCl2 solutions. The disperson of collagen fibrils was observed in the residue extracted with 1.0 M MgCl2 solution by electron microscopy; the fibril structure of collagen was disordered by extraction with 2.0 and 3.0 M MgCl2. The results suggest that the dispersion and disorder of collagen fibrils lead to the release of a non-collagenous protein. Furthermore, it is suggested that the removal of hyaluronic acid and dermatan sulfate was not very effective for the solubilization of a large amount of collagen, but was suitable as a pretreatment to the extraction of a non-collagenous protein accompanied by the solubilization of a large amount of collagen. 3. The non-collagenous protein was purified by DEAE-cellulose column chromatography. Polyacrylamide gel electrophoresis of this protein at pH 8.5 showed a single band moving to the cathode. The non-collagenous protein contained 3.7% hexose, 1.8% hexosamine, and no hexuronic acid. This protein is rich in glycine, glutamic acid, and alanine, and contains neither hydroxyproline nor hydroxylysine. Sedimentation analysis showed a single peak with 1.8 S and the molecular weight was approx. 43,000 as determided by SDS polyacrylamide gel electrophoresis."}
{"id": "PMID:7552", "title": "Altered prephenate dehydratase in phenylalanine-excreting mutants of Brevibacterium flavum.", "content": "The regulatory properties of three key enzymes in the phenylalanine biosynthetic pathway, 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase (DAHP synthetase) [EC 4.1.2.15], chorismate mutase [EC 5.4.99.5], and prephenate dehydratase [prephenate hydro-lyase (decarboxylating), EC 4.2.1.51] were compared in three phenylalanine-excreting mutants and the wild strain of Brevibacterium flavum. Regulation of DAHP synthetase by phenylalanine and tyrosine in these mutants did not change at all, but the specific activities of the mutant cell extracts increased 1.3- to 2.8-fold, as reported previously (1). Chorismate mutase activities in both the wild and the mutant strains were cumulatively inhibited by phenylalanine and tyrosine and recovered with tryptophan, while the specific activities of the mutants increased 1.3- to 2.8-fold, like those of DAHP synthetase. On the other hand, the specific activities of prephenate dehydratase in the mutant and wild strains were similar, when tyrosine was present. While prephenate dehydratase of the wild strain was inhibited by phenylalanine, tryptophan, and several phenylalanine analogues, the mutant enzymes were not inhibited at all but were activated by these effectors. Tyrosine activated the mutant enzymes much more strongly than the wild-type enzyme: in mutant 221-43, 1 mM tyrosine caused 28-fold activation. Km and the activation constant for tyrosine were slightly altered to a half and 6-fold compared with the wild-type enzyme, respectively, while the activation constants for phenylalanine and tryptophan were 500-fold higher than the respective inhibition constants of the wild-type enzyme. The molecular weight of the mutant enzyme was estimated to be 1.2 x 10(5), a half of that of the wild-type enzyme. The molecular weight of the mutant enzyme was estimated to be 1.2 X 10(5) a half of that of the wild type enzyme, while in the presence of tyrosine, phenylalanine, or tryptophan, it increased to that of the wild-type enzyme. Immediately after the mutant enzyme had been activated by tyrosine and then the tyrosine removed, it still showed about 10-fold higher specific activity than before the activation by tyrosine. However, on standing in ice the activity gradually fell to the initial level before the activation by tyrosine. Ammonium sulfate promoted the decrease of the activity. On the basis of these results, regulatory mechanisms for phenylalanine biosynthesis in vivo as well as mechanisms for the phenylalanine overproduction in the mutants are discussed.", "contents": "Altered prephenate dehydratase in phenylalanine-excreting mutants of Brevibacterium flavum. The regulatory properties of three key enzymes in the phenylalanine biosynthetic pathway, 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase (DAHP synthetase) [EC 4.1.2.15], chorismate mutase [EC 5.4.99.5], and prephenate dehydratase [prephenate hydro-lyase (decarboxylating), EC 4.2.1.51] were compared in three phenylalanine-excreting mutants and the wild strain of Brevibacterium flavum. Regulation of DAHP synthetase by phenylalanine and tyrosine in these mutants did not change at all, but the specific activities of the mutant cell extracts increased 1.3- to 2.8-fold, as reported previously (1). Chorismate mutase activities in both the wild and the mutant strains were cumulatively inhibited by phenylalanine and tyrosine and recovered with tryptophan, while the specific activities of the mutants increased 1.3- to 2.8-fold, like those of DAHP synthetase. On the other hand, the specific activities of prephenate dehydratase in the mutant and wild strains were similar, when tyrosine was present. While prephenate dehydratase of the wild strain was inhibited by phenylalanine, tryptophan, and several phenylalanine analogues, the mutant enzymes were not inhibited at all but were activated by these effectors. Tyrosine activated the mutant enzymes much more strongly than the wild-type enzyme: in mutant 221-43, 1 mM tyrosine caused 28-fold activation. Km and the activation constant for tyrosine were slightly altered to a half and 6-fold compared with the wild-type enzyme, respectively, while the activation constants for phenylalanine and tryptophan were 500-fold higher than the respective inhibition constants of the wild-type enzyme. The molecular weight of the mutant enzyme was estimated to be 1.2 x 10(5), a half of that of the wild-type enzyme. The molecular weight of the mutant enzyme was estimated to be 1.2 X 10(5) a half of that of the wild type enzyme, while in the presence of tyrosine, phenylalanine, or tryptophan, it increased to that of the wild-type enzyme. Immediately after the mutant enzyme had been activated by tyrosine and then the tyrosine removed, it still showed about 10-fold higher specific activity than before the activation by tyrosine. However, on standing in ice the activity gradually fell to the initial level before the activation by tyrosine. Ammonium sulfate promoted the decrease of the activity. On the basis of these results, regulatory mechanisms for phenylalanine biosynthesis in vivo as well as mechanisms for the phenylalanine overproduction in the mutants are discussed."}
{"id": "PMID:7553", "title": "Two glycosulfatases from the liver of a marine gastropod, Charonia lampas. Partial purification and properties.", "content": "Two glycosulfatases [EC 3.1.6.3], I and II, were purified 31.3- and 33.9-fold respectively, from a crude extract of the liver of Charonia lampas. The purification was carried out by the following chromatographic procedures; phosphocellulose, Sephadex G-150, Concanavalin A-Sepharose and isoelectric focussing. The enzyme preparations obtained were practically free from arylsulfatase [EC 3.1.6.1] contamination. Both glycosulfatases are probably glycoproteins differing in their carbohydrate moieties. The molecular weights of glycosulfatase I and II were estimated to be about 112,000 and 79,000 respectively. They had the same optimum pH of 5.5, and the same Km value of 25.0 mM for glucose 6-sulfate.", "contents": "Two glycosulfatases from the liver of a marine gastropod, Charonia lampas. Partial purification and properties. Two glycosulfatases [EC 3.1.6.3], I and II, were purified 31.3- and 33.9-fold respectively, from a crude extract of the liver of Charonia lampas. The purification was carried out by the following chromatographic procedures; phosphocellulose, Sephadex G-150, Concanavalin A-Sepharose and isoelectric focussing. The enzyme preparations obtained were practically free from arylsulfatase [EC 3.1.6.1] contamination. Both glycosulfatases are probably glycoproteins differing in their carbohydrate moieties. The molecular weights of glycosulfatase I and II were estimated to be about 112,000 and 79,000 respectively. They had the same optimum pH of 5.5, and the same Km value of 25.0 mM for glucose 6-sulfate."}
{"id": "PMID:7554", "title": "Comparative studies on polyguanylate polymerase and polyadenylate polymerase activities in the DNA-dependent RNA polymerase I fraction from cauliflower.", "content": "The properties of poly(G) polymerase and poly(A) polymerase activities in the DNA-dependent RNA polymerase [nucleosidetriphosphate: RNA nucleotidyltransferase EC 2.7.7.6] I fraction from cauliflower (Brassica oleracea var. botrytis) were comparatively investigated. The pH optimum, the effect of ionic strength, the effect of substrate concentration on the rate of synthesis, the effect of divalent metal ion concentration, and the time course of synthesis at different temperatures were all different for the three polymerase activities. The enzyme fraction preferentially utilized denatured DNA. Synthetic poly(C) and poly(U) were more effectively utillized for the synthesis of polyguanylate and polyadenylate, respectively. Further, it was found that poly(G) and poly(A) formed in vitro by the enzyme fraction had chain length of 25-28 and 84-89 nucleotides, respectively, and that poly (adenylate-gluanylate) chain was hardly formed when ATP and GTP were added together as substrates in the same reaction medium.", "contents": "Comparative studies on polyguanylate polymerase and polyadenylate polymerase activities in the DNA-dependent RNA polymerase I fraction from cauliflower. The properties of poly(G) polymerase and poly(A) polymerase activities in the DNA-dependent RNA polymerase [nucleosidetriphosphate: RNA nucleotidyltransferase EC 2.7.7.6] I fraction from cauliflower (Brassica oleracea var. botrytis) were comparatively investigated. The pH optimum, the effect of ionic strength, the effect of substrate concentration on the rate of synthesis, the effect of divalent metal ion concentration, and the time course of synthesis at different temperatures were all different for the three polymerase activities. The enzyme fraction preferentially utilized denatured DNA. Synthetic poly(C) and poly(U) were more effectively utillized for the synthesis of polyguanylate and polyadenylate, respectively. Further, it was found that poly(G) and poly(A) formed in vitro by the enzyme fraction had chain length of 25-28 and 84-89 nucleotides, respectively, and that poly (adenylate-gluanylate) chain was hardly formed when ATP and GTP were added together as substrates in the same reaction medium."}
{"id": "PMID:7555", "title": "Studies on the molecular species of DNA polymerase extracted from rat ascites hepatoma cells.", "content": "DNA polymerase [EC 2.7.7.7] activities present in hypotonic extract from rat ascites hepatoma AH130 cells were eluted in three separable peaks on DEAE-cellulose column chromatography. Peak I activity had an alkaline pH optimum, and was relatively resistant to SH-blocking reagents and salt concentration. These properties of DEAE peak I are typical of low molecular weight DNA polymerase. DEAE peak II and peak III activities possessed properties corresponding to high molecular weight (6-8 S) polymerase; they showed maximal activity at neutral pH, and were sensitive to SH-blocking reagents and salt. No low molecular weight polymerase activity was released from DEAE peak II or peak III by salt treatment, though partial conversion from DEAE peak II to peak III was observed on the same treatment.", "contents": "Studies on the molecular species of DNA polymerase extracted from rat ascites hepatoma cells. DNA polymerase [EC 2.7.7.7] activities present in hypotonic extract from rat ascites hepatoma AH130 cells were eluted in three separable peaks on DEAE-cellulose column chromatography. Peak I activity had an alkaline pH optimum, and was relatively resistant to SH-blocking reagents and salt concentration. These properties of DEAE peak I are typical of low molecular weight DNA polymerase. DEAE peak II and peak III activities possessed properties corresponding to high molecular weight (6-8 S) polymerase; they showed maximal activity at neutral pH, and were sensitive to SH-blocking reagents and salt. No low molecular weight polymerase activity was released from DEAE peak II or peak III by salt treatment, though partial conversion from DEAE peak II to peak III was observed on the same treatment."}
{"id": "PMID:7556", "title": "Formation of interchain disulfide bonds in Bence Jones proteins and immunoglobulins.", "content": "The formation of the interchain disulfide bonds in partially reduced Bence Jones proteins and immunoglobulins was studied in the presence of glutathione. It was found that only oxidized glutathione (GSSG) was effective for the formation of the interchain disulfide bonds in type gamma Bence Jones proteins and IgG. In type kappa Bence Jones proteins, on the other hand, no formation of the inter L-L disulfide bond was observed in the presence of GSSG at above pH 6. The kinetic pattern of disulfide bond formation of Bence Jones proteins was well interpreted by assuming that two monomers of a type gamma protein dimer are discriminated (monomers 1 and 2) and that only an intermediate in which the SH group on monomer 1 is blocked with GSSG can form a disulfide-bonded dimer and the intermediate in which the SH group on monomer 2 is blocked with GSSG can not. Comparison of the kinetic data for the formation of the interchain disulfide bonds of IgG with those for Bence Jones proteins suggested that H chain-GSSG mixed disulfide is a principal intermediate for the formation of the inter H-L disulfide bond.", "contents": "Formation of interchain disulfide bonds in Bence Jones proteins and immunoglobulins. The formation of the interchain disulfide bonds in partially reduced Bence Jones proteins and immunoglobulins was studied in the presence of glutathione. It was found that only oxidized glutathione (GSSG) was effective for the formation of the interchain disulfide bonds in type gamma Bence Jones proteins and IgG. In type kappa Bence Jones proteins, on the other hand, no formation of the inter L-L disulfide bond was observed in the presence of GSSG at above pH 6. The kinetic pattern of disulfide bond formation of Bence Jones proteins was well interpreted by assuming that two monomers of a type gamma protein dimer are discriminated (monomers 1 and 2) and that only an intermediate in which the SH group on monomer 1 is blocked with GSSG can form a disulfide-bonded dimer and the intermediate in which the SH group on monomer 2 is blocked with GSSG can not. Comparison of the kinetic data for the formation of the interchain disulfide bonds of IgG with those for Bence Jones proteins suggested that H chain-GSSG mixed disulfide is a principal intermediate for the formation of the inter H-L disulfide bond."}
{"id": "PMID:7557", "title": "Studies on alpha-amylase from a thermophilic bacterium. II. Thermal stability of the thermophilic alpha-amylase.", "content": "The effect of pH, mental ions, and denaturing reagents on the thermal stability of thermophilic alpha-amylase [EC 3.2.1.1] were examined. The enzyme was most stable at around pH 9.2, which is coincident with the isoelectric point of the enzyme. The stability of the enzyme was increased by the addition of calcium, strontium, and sodium ions. The addition of calcium ions markedly stabilized the enzyme. The protective effects of calcium and sodium ions were additive. At room temperature, no detectable destruction of the helical structure of the enzyme was observed after incubation for 1 hr in the presence of 1% sodium dodecylsulfate, 8 M urea or 6 M guanidine-HC1. The addition of 8 M urea or 6 M guanidine-HC1 lowered the thermal denaturation temperature of the enzyme. The enzyme contained one atom of tightly bound intrinsic calcium per molecule which could not be removed by electrodialysis unless the enzyme was denatured. The rate constants of inactivation and denaturation reactions in the absence and presence of calcium ions were measured and thermodynamic parameters were determined. The presence of calcium ions caused a remarkable decrease in the activation entropy.", "contents": "Studies on alpha-amylase from a thermophilic bacterium. II. Thermal stability of the thermophilic alpha-amylase. The effect of pH, mental ions, and denaturing reagents on the thermal stability of thermophilic alpha-amylase [EC 3.2.1.1] were examined. The enzyme was most stable at around pH 9.2, which is coincident with the isoelectric point of the enzyme. The stability of the enzyme was increased by the addition of calcium, strontium, and sodium ions. The addition of calcium ions markedly stabilized the enzyme. The protective effects of calcium and sodium ions were additive. At room temperature, no detectable destruction of the helical structure of the enzyme was observed after incubation for 1 hr in the presence of 1% sodium dodecylsulfate, 8 M urea or 6 M guanidine-HC1. The addition of 8 M urea or 6 M guanidine-HC1 lowered the thermal denaturation temperature of the enzyme. The enzyme contained one atom of tightly bound intrinsic calcium per molecule which could not be removed by electrodialysis unless the enzyme was denatured. The rate constants of inactivation and denaturation reactions in the absence and presence of calcium ions were measured and thermodynamic parameters were determined. The presence of calcium ions caused a remarkable decrease in the activation entropy."}
{"id": "PMID:7558", "title": "Activation process of pepsinogen.", "content": "The activation process of pepsinogen was analyzed by a combination of computer simulation and experiment. In order to investigate in detail the behavior of the basic schemes proposed in the previous study, further computer simulations were conducted. Some experiments were performed based on the information obtained. The changes in the UV difference spectrum in the early stage was measured by the stopped-flow technique and the conversion of pepsinogen to pepsin [EC 3.4.23.1] was followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Furthermore, on the basis of the experimental results, the most reasonable scheme was selected and modified. As a result, a scheme for the activation process of pepsinogen was obtained (Scheme 8). On the basis of the above analyses, it was assumed that the first step and the third step are pH-dependent based on the change in the UV spectrum, that the second step is a nonlinear reaction containing a looped reaction with a dimeric intermediate (in this step, peptide fragments are released and pepsinogen is converted to a pepsin-like molecule), and that the third step is an equilibrium reaction involving proton binding.", "contents": "Activation process of pepsinogen. The activation process of pepsinogen was analyzed by a combination of computer simulation and experiment. In order to investigate in detail the behavior of the basic schemes proposed in the previous study, further computer simulations were conducted. Some experiments were performed based on the information obtained. The changes in the UV difference spectrum in the early stage was measured by the stopped-flow technique and the conversion of pepsinogen to pepsin [EC 3.4.23.1] was followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Furthermore, on the basis of the experimental results, the most reasonable scheme was selected and modified. As a result, a scheme for the activation process of pepsinogen was obtained (Scheme 8). On the basis of the above analyses, it was assumed that the first step and the third step are pH-dependent based on the change in the UV spectrum, that the second step is a nonlinear reaction containing a looped reaction with a dimeric intermediate (in this step, peptide fragments are released and pepsinogen is converted to a pepsin-like molecule), and that the third step is an equilibrium reaction involving proton binding."}
{"id": "PMID:7559", "title": "An oxygraphic method for the determination of cholesterol and measurement of the slow oxygen-consuming reactions of hepatic microsomes.", "content": "Oxygen-consuming reactions of cholesterol oxidase [EC 1.1.3.6] and microsomes were measured with a galvanic oxygen electrode which was attached to an offset amplifier for sensitive measurement of the reaction processes. The sensitivity of this oxygraphic method for detection of oxygen consumption was ten times greater than that of the usual method. The minimum rate of slow oxygen-consuming reactions which could be estimated was about 5 nmoles of oxygen per min, and the minimum amount of oxygen consumption which could be determined was also about 5 nmoles. An oxygraphic method for direct and rapid determination of cholesterol was demonstrated using one-twentieth the amount of cholesterol oxidase which is used for the colorimetric method. The processes of cyanide-suppressed beta-NADH-dependent oxygen consumption and cyanide-insensitive alpha-NADH-dependent oxygen consumption, which were difficult to follow by the usual method, were followed using a small amount of microsomes (less than 1mg protein/ml). Furthermore, the temporary cessation of alpha-NADH-dependent oxygen consumption caused by ferricyanide and the corresponding oxidation-reduction of reduced cytochrome b5 were followed in the presence of ADP. ADP did not inhibit the oxygen consumption. The results indicate that the oxygen consumption with alpha-NADH is due to electron transfer from alpha-NADH via NADH-cytochrome b5 reductase and cytochrome b5, in which the rate-determining step lies at some reaction after the reduction of cytochrome b5.", "contents": "An oxygraphic method for the determination of cholesterol and measurement of the slow oxygen-consuming reactions of hepatic microsomes. Oxygen-consuming reactions of cholesterol oxidase [EC 1.1.3.6] and microsomes were measured with a galvanic oxygen electrode which was attached to an offset amplifier for sensitive measurement of the reaction processes. The sensitivity of this oxygraphic method for detection of oxygen consumption was ten times greater than that of the usual method. The minimum rate of slow oxygen-consuming reactions which could be estimated was about 5 nmoles of oxygen per min, and the minimum amount of oxygen consumption which could be determined was also about 5 nmoles. An oxygraphic method for direct and rapid determination of cholesterol was demonstrated using one-twentieth the amount of cholesterol oxidase which is used for the colorimetric method. The processes of cyanide-suppressed beta-NADH-dependent oxygen consumption and cyanide-insensitive alpha-NADH-dependent oxygen consumption, which were difficult to follow by the usual method, were followed using a small amount of microsomes (less than 1mg protein/ml). Furthermore, the temporary cessation of alpha-NADH-dependent oxygen consumption caused by ferricyanide and the corresponding oxidation-reduction of reduced cytochrome b5 were followed in the presence of ADP. ADP did not inhibit the oxygen consumption. The results indicate that the oxygen consumption with alpha-NADH is due to electron transfer from alpha-NADH via NADH-cytochrome b5 reductase and cytochrome b5, in which the rate-determining step lies at some reaction after the reduction of cytochrome b5."}
{"id": "PMID:7560", "title": "Purification and properties of cathepsin D from porcine spleen.", "content": "Cathepsin D was purified from porcine spleen to near homogeneity as determined by gel electrophoresis. The isolation scheme involved an acid precipitation of tissue extract, DEAE-cellulose and Sephadex G-200 chromatography, and isoelectric focusing. The end product represented about a 1000-fold purification and about a 10% recovery. The purified enzyme was the major isoenzyme, which represented 60% of cathepsin D present in porcine spleen. Two minor isoenzymes of cathepsin D were present in small amounts. The purified enzyme resembled porcine pepsin in molecular weight (35,000), amino acid composition, and inactivation by specific pepsin inactivators. The pH activity curve of the purified enzyme showed two optima near pH 3 and 4. The relative activities at these optimal pH values were affected by salt concentration. Experimental evidence indicated that the two-optima phenomenon is a property of a single enzyme species.", "contents": "Purification and properties of cathepsin D from porcine spleen. Cathepsin D was purified from porcine spleen to near homogeneity as determined by gel electrophoresis. The isolation scheme involved an acid precipitation of tissue extract, DEAE-cellulose and Sephadex G-200 chromatography, and isoelectric focusing. The end product represented about a 1000-fold purification and about a 10% recovery. The purified enzyme was the major isoenzyme, which represented 60% of cathepsin D present in porcine spleen. Two minor isoenzymes of cathepsin D were present in small amounts. The purified enzyme resembled porcine pepsin in molecular weight (35,000), amino acid composition, and inactivation by specific pepsin inactivators. The pH activity curve of the purified enzyme showed two optima near pH 3 and 4. The relative activities at these optimal pH values were affected by salt concentration. Experimental evidence indicated that the two-optima phenomenon is a property of a single enzyme species."}
{"id": "PMID:7561", "title": "Regulation of the transmembrane potential of isolated chromaffin granules by ATP, ATP analogs, and external pH.", "content": "The transmembrane potential of isolated chromaffin granules has been measured using the permeant ions [14C]methylamine and [35S]thiocyanate, as well as the fluorescent probe, 9-aminoacridine. At pH 7.0, the granule membrane had a Nernst proton potential of -45mV, inside negative. This potential was sensitive to the external pH, but was unaffected by K+,Na+, Ca2+, Mg2+, or other cations. The pH of zero potential was 6.25 for both methylamine and thiocyanate. Thiocyanate also had a Nernst potential of similar magnitude and sign to that of methylamine at pH 7.0, and was also sensitive to variation in external pH. Mg2+ATP was found to depolarize the granule membrane by a saturable mechanism with a K 1/2 for ATP of 40 muM. Ca2+ was only 30% as effective as Mg2+ in supporting the ATP effect. The pH optimum for this process was 6.25 and appeared to be accompanied by a marked alkalinization of the granule interior. The specificity for ATP was further tested with structural analogs of ATP and GTP. The rate of change of membrane potential in response to changes in external pH or Mg2+ATP was estimated using the fluorescent probe 9-aminoacridine. Changes came to completion in less than 1 s. This suggested that the ATP effects were not dependent on an enzymatic transformation but on an ATP-induced conformational change in the membrane. We conclude that the chromaffin granule exists in at least two proton permeability states, corresponding to the presence or absence of Mg2+ATP. These states may be related to hormone release from granules and regulation of secretion in vivo.", "contents": "Regulation of the transmembrane potential of isolated chromaffin granules by ATP, ATP analogs, and external pH. The transmembrane potential of isolated chromaffin granules has been measured using the permeant ions [14C]methylamine and [35S]thiocyanate, as well as the fluorescent probe, 9-aminoacridine. At pH 7.0, the granule membrane had a Nernst proton potential of -45mV, inside negative. This potential was sensitive to the external pH, but was unaffected by K+,Na+, Ca2+, Mg2+, or other cations. The pH of zero potential was 6.25 for both methylamine and thiocyanate. Thiocyanate also had a Nernst potential of similar magnitude and sign to that of methylamine at pH 7.0, and was also sensitive to variation in external pH. Mg2+ATP was found to depolarize the granule membrane by a saturable mechanism with a K 1/2 for ATP of 40 muM. Ca2+ was only 30% as effective as Mg2+ in supporting the ATP effect. The pH optimum for this process was 6.25 and appeared to be accompanied by a marked alkalinization of the granule interior. The specificity for ATP was further tested with structural analogs of ATP and GTP. The rate of change of membrane potential in response to changes in external pH or Mg2+ATP was estimated using the fluorescent probe 9-aminoacridine. Changes came to completion in less than 1 s. This suggested that the ATP effects were not dependent on an enzymatic transformation but on an ATP-induced conformational change in the membrane. We conclude that the chromaffin granule exists in at least two proton permeability states, corresponding to the presence or absence of Mg2+ATP. These states may be related to hormone release from granules and regulation of secretion in vivo."}
{"id": "PMID:7562", "title": "Studies on the subcellular localization and properties of bis(monoacylglyceryl)phosphate biosynthesis in rat liver.", "content": "Phosphatidylglycerol conversion to bis(monoacylglyceryl)phosphate by rat liver homogenate was studied and maximum rates of synthesis were observed at pH 4.4. The distribution of bis(monoacylglyceryl)P synthetase in rat liver subcellular fractions was determined, and evidence is presented establishing the lysosomes as the site of bis(monoacylglyceryl)P synthesis. In addition to phosphatidylglycerol, 1-acyl- and 2-acyllysophosphatidylglycerol also served as precursors for bis(monoacylglyceryl)P with lysosomes as an enzyme source. Bis(monoacylglyceryl)P synthesis did not require high energy intermediates or cofactors. The possibility that a lysosomal phospholipase A with acyl transferase activity catalyzes the formation of bis(monoacylglyceryl)P was investigated. Heat stability and inhibitor studies suggested that this is probably not the case. Lysosomes were shown to be unable to synthesize phosphatidylglycerol, and lipid analyses showed that lysosomes do not contain phosphatidylglycerol or lysophosphatidylglycerol. Bis(monoacylglyceryl)P synthesis in the cell may require the interaction of lysosomes with a phosphatidylglycerol-containing membrane.", "contents": "Studies on the subcellular localization and properties of bis(monoacylglyceryl)phosphate biosynthesis in rat liver. Phosphatidylglycerol conversion to bis(monoacylglyceryl)phosphate by rat liver homogenate was studied and maximum rates of synthesis were observed at pH 4.4. The distribution of bis(monoacylglyceryl)P synthetase in rat liver subcellular fractions was determined, and evidence is presented establishing the lysosomes as the site of bis(monoacylglyceryl)P synthesis. In addition to phosphatidylglycerol, 1-acyl- and 2-acyllysophosphatidylglycerol also served as precursors for bis(monoacylglyceryl)P with lysosomes as an enzyme source. Bis(monoacylglyceryl)P synthesis did not require high energy intermediates or cofactors. The possibility that a lysosomal phospholipase A with acyl transferase activity catalyzes the formation of bis(monoacylglyceryl)P was investigated. Heat stability and inhibitor studies suggested that this is probably not the case. Lysosomes were shown to be unable to synthesize phosphatidylglycerol, and lipid analyses showed that lysosomes do not contain phosphatidylglycerol or lysophosphatidylglycerol. Bis(monoacylglyceryl)P synthesis in the cell may require the interaction of lysosomes with a phosphatidylglycerol-containing membrane."}
{"id": "PMID:7563", "title": "Properties of the guanylate cyclase-guanosine 3':5'-monophosphate system of rat renal cortex. Activation of guanylate cyclase and calcium-independent modulation of tissue guanosine 3':5'-monophosphate by sodium azide.", "content": "The effects of sodium azide on guanylate cyclase activity of homogenates of rat renal cortex and on the guanosine 3':5'-monophosphate (cGMP) content of cortical slices were examined and compared to those of carbamylcholine and NaF. In complete Krebs-Ringer bicarbonate buffer containing 10 mM theophylline, tissue cGMP content was increased 5- to 6-fold by 0.05 mM carbamylcholine or 10 mM NaN3, and 3-fold by 10 mM NaF. Increases in cGMP were maximal in response to these concentrations of the agonists and occurred within 2 min. Exclusion of Ca2+ from the incubation media reduced basal cGMP by 50% in 20 min and abolished responses to carbamylcholine and NaF, while exclusion of Mg2+ was without effect. Analogous reductions in cGMP were observed in complete buffer containing 1 mM tetracaine, an agent which blocks movement of Ca2+ across and binding to biologic membranes. By contrast, exclusion of Ca2+ or addition of tetracaine did not alter relative cGMP responses to NaN3 (6-fold increase over basal), although levels were reduced in slices exposed to these buffers for 20 min. When slices were incubated without Ca2+ or with tetracaine for only 2 min prior to addition of agonists, basal cGMP did not decline. Under these conditions, both absolute and relative increases in cGMP in response to NaN3 were comparable to those of slices incubated throughout in complete buffer, while carbamylcholine and NaF effects on cGMP were abolished. NaN3 increased guanylate cyclase activity of whole homogenates (10- to 20-fold), and of the 100,000 X g soluble (20-fold) and particulate (4-fold) fractions of cortex. Prior incubation of slices with NaN3 in the presence or absence of Ca2+ or with Ca2+ plus tetracaine also markedly enhanced enzyme activity in homogenates and subcellular fractions subsequently prepared from these slices. In the presence of 3 mM excess MnCl2, NaN3 raised the apparent Km for MnGTP of soluble guanylate cyclase from 0.11 mM to 0.20 mM, and reduced enzyme dependence on Mn2+. Thus, when Mg2+ was employed as the sole divalent cation in the enzyme reaction mixture basal and NaN3-responsive activities were 7% and 30% of those seen with optimal concentrations of Mn2+, respectively. Under a variety of assay conditions where responses to NaN3 were readily detectable, alterations in guanylate cyclase activities could not be demonstrated in response to carbamylcholine or NaF. By contrast Ca2+ increased the guanylate cyclase activity 6- to 7-fold over basal under conditions of reduced Mn2+ (0.75 mM Mn2+/1 mM GTP). This latter effect of Ca2+ was shared by Mg2+ and not blocked by tetracaine. Carbamylcholine, NaF, Ca2+, and NaN3 all failed to alter cGMP phosphodiesterase activity in cortex. Thus, while carbamylcholine and NaF enhance renal cortical cGMP accumulation through actions which are dependent upon the presence of extracellular Ca2+, NaN3 stimulates cGMP generation in this tissue through an apparently distinct Ca2+-independent mechanism.", "contents": "Properties of the guanylate cyclase-guanosine 3':5'-monophosphate system of rat renal cortex. Activation of guanylate cyclase and calcium-independent modulation of tissue guanosine 3':5'-monophosphate by sodium azide. The effects of sodium azide on guanylate cyclase activity of homogenates of rat renal cortex and on the guanosine 3':5'-monophosphate (cGMP) content of cortical slices were examined and compared to those of carbamylcholine and NaF. In complete Krebs-Ringer bicarbonate buffer containing 10 mM theophylline, tissue cGMP content was increased 5- to 6-fold by 0.05 mM carbamylcholine or 10 mM NaN3, and 3-fold by 10 mM NaF. Increases in cGMP were maximal in response to these concentrations of the agonists and occurred within 2 min. Exclusion of Ca2+ from the incubation media reduced basal cGMP by 50% in 20 min and abolished responses to carbamylcholine and NaF, while exclusion of Mg2+ was without effect. Analogous reductions in cGMP were observed in complete buffer containing 1 mM tetracaine, an agent which blocks movement of Ca2+ across and binding to biologic membranes. By contrast, exclusion of Ca2+ or addition of tetracaine did not alter relative cGMP responses to NaN3 (6-fold increase over basal), although levels were reduced in slices exposed to these buffers for 20 min. When slices were incubated without Ca2+ or with tetracaine for only 2 min prior to addition of agonists, basal cGMP did not decline. Under these conditions, both absolute and relative increases in cGMP in response to NaN3 were comparable to those of slices incubated throughout in complete buffer, while carbamylcholine and NaF effects on cGMP were abolished. NaN3 increased guanylate cyclase activity of whole homogenates (10- to 20-fold), and of the 100,000 X g soluble (20-fold) and particulate (4-fold) fractions of cortex. Prior incubation of slices with NaN3 in the presence or absence of Ca2+ or with Ca2+ plus tetracaine also markedly enhanced enzyme activity in homogenates and subcellular fractions subsequently prepared from these slices. In the presence of 3 mM excess MnCl2, NaN3 raised the apparent Km for MnGTP of soluble guanylate cyclase from 0.11 mM to 0.20 mM, and reduced enzyme dependence on Mn2+. Thus, when Mg2+ was employed as the sole divalent cation in the enzyme reaction mixture basal and NaN3-responsive activities were 7% and 30% of those seen with optimal concentrations of Mn2+, respectively. Under a variety of assay conditions where responses to NaN3 were readily detectable, alterations in guanylate cyclase activities could not be demonstrated in response to carbamylcholine or NaF. By contrast Ca2+ increased the guanylate cyclase activity 6- to 7-fold over basal under conditions of reduced Mn2+ (0.75 mM Mn2+/1 mM GTP). This latter effect of Ca2+ was shared by Mg2+ and not blocked by tetracaine. Carbamylcholine, NaF, Ca2+, and NaN3 all failed to alter cGMP phosphodiesterase activity in cortex. Thus, while carbamylcholine and NaF enhance renal cortical cGMP accumulation through actions which are dependent upon the presence of extracellular Ca2+, NaN3 stimulates cGMP generation in this tissue through an apparently distinct Ca2+-independent mechanism."}
{"id": "PMID:7564", "title": "Requirement of an essential thiol group and ferric iron for the activity of the progesterone-induced porcine uterine purple phosphatase.", "content": "The progesterone-induced purple phosphatase isolated from the uterine flushings of pigs is activated by a variety of reagents that cleave disulfide bonds, including 2-mercaptoethanol, dithiothreitol, L-ascorbate, L-cysteine, sulfite, and cyanide. It is inhibited by various mercurials, iodoacetamide, O-iodosobenzoate, and hydrogen peroxide. Thiols increase the specific phosphatase activity from 25 to about 300 units per mg of enzyme. This activation is accompanied by a shift in the extinction maximum to higher energy to yield a protein with a pink coloration. Following maximum activation there is a gradual decrease in enzyme activity and protein color which is accompanied by loss of ferrous iron from the protein. Sodium dithionite at 10 mM or higher causes an immediate inhibition of phosphatase activity and bleaching of color, and can be used to prepare the iron-free apoprotein. The latter can be partially reactivated by Fe3+ salts but not by Fe2+. The Fe3+ restores the pink form of the enzyme with a specific activity of about 200 units/mg of protein. Cu2+ also causes some reactivation, but other metal ions were ineffective. ESR studies showed that the pink form of phosphatase contains approximately 1 atom of high spin ferric iron per molecule. It is concluded that the phosphatase requires a free thiol and Fe3+ for activity. Reduction of the iron leads to complete loss of both color and enzyme activity. The color change from purple to pink represents disulfide reduction and is not due to reduction of iron.", "contents": "Requirement of an essential thiol group and ferric iron for the activity of the progesterone-induced porcine uterine purple phosphatase. The progesterone-induced purple phosphatase isolated from the uterine flushings of pigs is activated by a variety of reagents that cleave disulfide bonds, including 2-mercaptoethanol, dithiothreitol, L-ascorbate, L-cysteine, sulfite, and cyanide. It is inhibited by various mercurials, iodoacetamide, O-iodosobenzoate, and hydrogen peroxide. Thiols increase the specific phosphatase activity from 25 to about 300 units per mg of enzyme. This activation is accompanied by a shift in the extinction maximum to higher energy to yield a protein with a pink coloration. Following maximum activation there is a gradual decrease in enzyme activity and protein color which is accompanied by loss of ferrous iron from the protein. Sodium dithionite at 10 mM or higher causes an immediate inhibition of phosphatase activity and bleaching of color, and can be used to prepare the iron-free apoprotein. The latter can be partially reactivated by Fe3+ salts but not by Fe2+. The Fe3+ restores the pink form of the enzyme with a specific activity of about 200 units/mg of protein. Cu2+ also causes some reactivation, but other metal ions were ineffective. ESR studies showed that the pink form of phosphatase contains approximately 1 atom of high spin ferric iron per molecule. It is concluded that the phosphatase requires a free thiol and Fe3+ for activity. Reduction of the iron leads to complete loss of both color and enzyme activity. The color change from purple to pink represents disulfide reduction and is not due to reduction of iron."}
{"id": "PMID:7565", "title": "Distribution of enzyme activities in subcellular fractions of bovine retina.", "content": "Centrifugation of homogenates of bovine retinas to isopycnic equilibrium in sucrose density gradients yielded three partially overlapping bands of particles which were, in the order of increasing density: (a) photoreceptor cell (rod) outer segments; (b) plasma membranes, lysosomes, and large fragments of endoplasmic reticulum; and (c) mitochondria. The only enzyme activity investigated which had a peak coinciding only with outer segment fractions was guanylate cyclase. Enzyme activities with peaks in both the outer segment and denser fractions included 5'-nucleotidase and cyclic GMP phosphodiesterase. Enzyme activities with peaks only in the denser fractions included sodium and potassium ion-activated ATPase ((Na+ + K+)-ATPase), adenylate cyclase, cyclic AMP phosphodiesterase, beta-glucosidase, beta-galactosidase, and succinate-dependent cytochrome c reductase. These results suggest that some of the activities once thought to be present in rod outer segments are actually present in particles from elsewhere in the retina which contaminate rod outer segment preparations.", "contents": "Distribution of enzyme activities in subcellular fractions of bovine retina. Centrifugation of homogenates of bovine retinas to isopycnic equilibrium in sucrose density gradients yielded three partially overlapping bands of particles which were, in the order of increasing density: (a) photoreceptor cell (rod) outer segments; (b) plasma membranes, lysosomes, and large fragments of endoplasmic reticulum; and (c) mitochondria. The only enzyme activity investigated which had a peak coinciding only with outer segment fractions was guanylate cyclase. Enzyme activities with peaks in both the outer segment and denser fractions included 5'-nucleotidase and cyclic GMP phosphodiesterase. Enzyme activities with peaks only in the denser fractions included sodium and potassium ion-activated ATPase ((Na+ + K+)-ATPase), adenylate cyclase, cyclic AMP phosphodiesterase, beta-glucosidase, beta-galactosidase, and succinate-dependent cytochrome c reductase. These results suggest that some of the activities once thought to be present in rod outer segments are actually present in particles from elsewhere in the retina which contaminate rod outer segment preparations."}
{"id": "PMID:7566", "title": "Kinetic studies of sheep kidney gamma-glutamyl transpeptidase.", "content": "The kinetics of sheep kidney gamma-glutamyl transpeptidase was studied using a novel substrate L-alpha-methyl-gamma-glutamyl-L-alpha-aminobutyrate. When the substrate was incubated with the enzyme in the presence of an amino acid or peptide acceptor, the corresponding L-alpha-methyl-gamma-glutamyl derivatives of the acceptors were formed. In the absence of acceptor only hydrolysis occurred, and no transpeptidation products were detected. The presence of the methyl group on the alpha-carbon apparently prevents enzymatic transfer of the L-alpha-methyl-gamma-glutamyl residue to the amino group of the substrate itself (autotranspeptidation). When the enzyme was incubated with conventional substrates, such as glutathione or gamma-glutamyl-p-nitroanilide and an amino acid acceptor, hydrolysis, autotranspeptidation, and transpeptidation to the acceptor occurred concurrently. Initial velocity measurements in which the concentration of L-alpha-methyl-gamma-glutamyl-L-alpha-aminobutyrate was varied at several fixed acceptor concentrations, and either the release of alpha-aminobutyrate or the formation of the transpeptidation products was determined, yielded results which are consistent with a ping-pong mechanism modified by a hydrolytic shunt. A scheme of such a mechanism is presented. This mechanism predicts the formation of an alpha-methyl-gamma-glutamyl-enzyme intermediate, which can react with an amino acid to form the transpeptidation product; or in the absence of, or in the presence of low concentrations of amino acids, can react with water to form the hydrolytic products. Kinetic derivations for the reaction of the enzyme with the conventional substrate gamma-glutamyl-p-nitroanilide predict either linear or nonlinear double-reciprocal plots, depending on the prevalence of the hydrolytic, autotranspeptidation, or transpeptidation reactions. The results of kinetic experiments confirmed these predictions.", "contents": "Kinetic studies of sheep kidney gamma-glutamyl transpeptidase. The kinetics of sheep kidney gamma-glutamyl transpeptidase was studied using a novel substrate L-alpha-methyl-gamma-glutamyl-L-alpha-aminobutyrate. When the substrate was incubated with the enzyme in the presence of an amino acid or peptide acceptor, the corresponding L-alpha-methyl-gamma-glutamyl derivatives of the acceptors were formed. In the absence of acceptor only hydrolysis occurred, and no transpeptidation products were detected. The presence of the methyl group on the alpha-carbon apparently prevents enzymatic transfer of the L-alpha-methyl-gamma-glutamyl residue to the amino group of the substrate itself (autotranspeptidation). When the enzyme was incubated with conventional substrates, such as glutathione or gamma-glutamyl-p-nitroanilide and an amino acid acceptor, hydrolysis, autotranspeptidation, and transpeptidation to the acceptor occurred concurrently. Initial velocity measurements in which the concentration of L-alpha-methyl-gamma-glutamyl-L-alpha-aminobutyrate was varied at several fixed acceptor concentrations, and either the release of alpha-aminobutyrate or the formation of the transpeptidation products was determined, yielded results which are consistent with a ping-pong mechanism modified by a hydrolytic shunt. A scheme of such a mechanism is presented. This mechanism predicts the formation of an alpha-methyl-gamma-glutamyl-enzyme intermediate, which can react with an amino acid to form the transpeptidation product; or in the absence of, or in the presence of low concentrations of amino acids, can react with water to form the hydrolytic products. Kinetic derivations for the reaction of the enzyme with the conventional substrate gamma-glutamyl-p-nitroanilide predict either linear or nonlinear double-reciprocal plots, depending on the prevalence of the hydrolytic, autotranspeptidation, or transpeptidation reactions. The results of kinetic experiments confirmed these predictions."}
{"id": "PMID:7567", "title": "Neurospora crassa glutamine synthetase. Purification by affinity chromatography and characterization of subunit structure.", "content": "Neurospora crassa glutamine synthetase was purified to homogeneity by a procedure based on affinity chromatography. The enzyme is adsorbed to a matrix of anthranilic acid bound to Sepharose and eluted with AMP. Different experimental approaches indicate that the enzyme has an octameric structure formed by subunits of identical molecular weight.", "contents": "Neurospora crassa glutamine synthetase. Purification by affinity chromatography and characterization of subunit structure. Neurospora crassa glutamine synthetase was purified to homogeneity by a procedure based on affinity chromatography. The enzyme is adsorbed to a matrix of anthranilic acid bound to Sepharose and eluted with AMP. Different experimental approaches indicate that the enzyme has an octameric structure formed by subunits of identical molecular weight."}
{"id": "PMID:7570", "title": "Chromatographic behaviour of alkaloids on thin layers of cation exchangers. II. Alginic acid, Rexyn 102, Dowex 50-X4 and CMCNa.", "content": "The chromatographic behaviour of 48 alkaloids on cation exchangers with cellulose, paraffin and polystyrene matrices in both the acid and sodium salt forms has been investigated. Water-organic solvent mixtures, aqueous buffer solutions and organic and mineral acid solutions in both water and in aqueous-organic solvents have been used as eluents. The retention mechanisms of these compounds on alginic acid, Rexyn 102 (Hplus) and Dowex 50-X4 (Hplus) thin layers are discussed. Interesting separations of the alkaloids were carried out on alginic acid and Rexyn 102 (Hplus).", "contents": "Chromatographic behaviour of alkaloids on thin layers of cation exchangers. II. Alginic acid, Rexyn 102, Dowex 50-X4 and CMCNa. The chromatographic behaviour of 48 alkaloids on cation exchangers with cellulose, paraffin and polystyrene matrices in both the acid and sodium salt forms has been investigated. Water-organic solvent mixtures, aqueous buffer solutions and organic and mineral acid solutions in both water and in aqueous-organic solvents have been used as eluents. The retention mechanisms of these compounds on alginic acid, Rexyn 102 (Hplus) and Dowex 50-X4 (Hplus) thin layers are discussed. Interesting separations of the alkaloids were carried out on alginic acid and Rexyn 102 (Hplus)."}
{"id": "PMID:7569", "title": "Membrane receptors for hormones and neurotransmitters.", "content": "Receptors for peptide hormones and neurotransmitters are integral components of the plasma membrane of cells which serve to couple the external milieu to the intracellular regulators of metabolism. These macromolecules are usually high molecular weight glycoproteins, and in many cases appear to have more than one subunit capable of binding the hormone. The interaction of the hormone or neurotransmitter with its receptor is rapid, reversible, and of high affinity and specificity. Many receptors exhibit cooperative properties in hormone binding or biological function. The concentration of receptors on the membrane is a function of continued synthesis and degradation, and may be altered by a variety of factors including the hormone itself. The fluid mosaic nature of the membrane may allow hormone receptors and effectors to exist in free floating states. Further investigations of the hormone-receptor interaction will no doubt yield new insights into both the mechanism of hormone action and membrane structure and function.", "contents": "Membrane receptors for hormones and neurotransmitters. Receptors for peptide hormones and neurotransmitters are integral components of the plasma membrane of cells which serve to couple the external milieu to the intracellular regulators of metabolism. These macromolecules are usually high molecular weight glycoproteins, and in many cases appear to have more than one subunit capable of binding the hormone. The interaction of the hormone or neurotransmitter with its receptor is rapid, reversible, and of high affinity and specificity. Many receptors exhibit cooperative properties in hormone binding or biological function. The concentration of receptors on the membrane is a function of continued synthesis and degradation, and may be altered by a variety of factors including the hormone itself. The fluid mosaic nature of the membrane may allow hormone receptors and effectors to exist in free floating states. Further investigations of the hormone-receptor interaction will no doubt yield new insights into both the mechanism of hormone action and membrane structure and function."}
{"id": "PMID:7571", "title": "Prolactin secretion by metoclopramide in man.", "content": "Six men and nine women were given intravenous injections of 2.5 mg of metoclopramide to assess its potential as a stimulus to prolactin release. Following the administration of metoclopramide, there was prompt increase in serum prolactin to a peak response of 38.2 +/- 3.9 ng/ml in men and 103 +/- 10.2 ng/ml in women. The prolactin response to metoclopramide in men was compared with the response to 400 mug of TRH in 10 men. The peak response after TRH was 22.4 +/- 2.2 ng/ml, which was significantly less than that observed after metoclopramide. Pretreatment with 500 mg of L-dopa suppressed the prolactin response to metoclopramide in 6 men to a mean response of 16.3 +/- 4.3 ng/ml. We have concluded that metoclopramide is a safe, reliable, and potent stimulus of prolactin secretion and exerts this effect by blocking dopamine receptors in the hypothalamus and decreasing prolactin inhibiting factor. It is free of side effects and is a useful alternative to chlorpromazine.", "contents": "Prolactin secretion by metoclopramide in man. Six men and nine women were given intravenous injections of 2.5 mg of metoclopramide to assess its potential as a stimulus to prolactin release. Following the administration of metoclopramide, there was prompt increase in serum prolactin to a peak response of 38.2 +/- 3.9 ng/ml in men and 103 +/- 10.2 ng/ml in women. The prolactin response to metoclopramide in men was compared with the response to 400 mug of TRH in 10 men. The peak response after TRH was 22.4 +/- 2.2 ng/ml, which was significantly less than that observed after metoclopramide. Pretreatment with 500 mg of L-dopa suppressed the prolactin response to metoclopramide in 6 men to a mean response of 16.3 +/- 4.3 ng/ml. We have concluded that metoclopramide is a safe, reliable, and potent stimulus of prolactin secretion and exerts this effect by blocking dopamine receptors in the hypothalamus and decreasing prolactin inhibiting factor. It is free of side effects and is a useful alternative to chlorpromazine."}
{"id": "PMID:7572", "title": "Deficient 17 beta-hydroxysteroid oxidoreductase activity in testes from a male pseudohermaphrodite.", "content": "17beta-Hydroxysteroid oxidoreductase (17 beta-HOR) activity in testicular tissue from a male pseudohermaphrodite (MP) who had elevated plasma LH and androstenedione (A) levels, and normal dehydroepiandrosterone (DHA) levels was compared by in vitro studies to that of testicular tissue from a normal man. The 17 beta-HOR activity from the MP was localized predominantly in the microsomal fraction, as it is in normal testicular tissue. With DHA, A, and estrone as substrates, the 17 beta-HOR activity of the MP was decreased in the presence of NADPH, but not NADH, in comparison with the normal. NADPH was the preferred co-factor for 17 beta-HOR from the normal testes, while 17 beta-HOR activity from the MP testes was less with NADPH than with NADH as cofactor. These results indicate that the inefficient testosterone production in the MP testes may be accounted for by a deficiency of NADPH-dependent 17 beta-HOR activity. Further studies suggested that 3 beta-hydroxysteroid oxidoreductase-isomerase (3 beta-HOR) was increased in the MP testes and was much greater than 17 beta-HOR activity with DHA as substrate. These findings largely explain the elevated plasma A levels with normal DHA levels, and suggest that DHA leads to A leads to testosterone was the major route of testosterone biosynthesis in the MP testes.", "contents": "Deficient 17 beta-hydroxysteroid oxidoreductase activity in testes from a male pseudohermaphrodite. 17beta-Hydroxysteroid oxidoreductase (17 beta-HOR) activity in testicular tissue from a male pseudohermaphrodite (MP) who had elevated plasma LH and androstenedione (A) levels, and normal dehydroepiandrosterone (DHA) levels was compared by in vitro studies to that of testicular tissue from a normal man. The 17 beta-HOR activity from the MP was localized predominantly in the microsomal fraction, as it is in normal testicular tissue. With DHA, A, and estrone as substrates, the 17 beta-HOR activity of the MP was decreased in the presence of NADPH, but not NADH, in comparison with the normal. NADPH was the preferred co-factor for 17 beta-HOR from the normal testes, while 17 beta-HOR activity from the MP testes was less with NADPH than with NADH as cofactor. These results indicate that the inefficient testosterone production in the MP testes may be accounted for by a deficiency of NADPH-dependent 17 beta-HOR activity. Further studies suggested that 3 beta-hydroxysteroid oxidoreductase-isomerase (3 beta-HOR) was increased in the MP testes and was much greater than 17 beta-HOR activity with DHA as substrate. These findings largely explain the elevated plasma A levels with normal DHA levels, and suggest that DHA leads to A leads to testosterone was the major route of testosterone biosynthesis in the MP testes."}
{"id": "PMID:7573", "title": "Counterimmunoelectrophoresis of staphylococcal antibody.", "content": "Modifications of the staphylococcal counterimmunoelectrophoresis technique were evaluated to determine how variations in the procedure affected results. Neither a buffer pH range of 7.8 to 9.0 nor buffer molarity of 0.015 or 0.025 when tested in combinations caused appreciable differences. However, use of different agar preparations or delay in addition of antigen to the test slide altered the location of the precipitin band. Agarose was found to be more sensitive in determining the serum precipitin titer and provided a better photographic record than either Ionagar or Noble agar.", "contents": "Counterimmunoelectrophoresis of staphylococcal antibody. Modifications of the staphylococcal counterimmunoelectrophoresis technique were evaluated to determine how variations in the procedure affected results. Neither a buffer pH range of 7.8 to 9.0 nor buffer molarity of 0.015 or 0.025 when tested in combinations caused appreciable differences. However, use of different agar preparations or delay in addition of antigen to the test slide altered the location of the precipitin band. Agarose was found to be more sensitive in determining the serum precipitin titer and provided a better photographic record than either Ionagar or Noble agar."}
{"id": "PMID:7574", "title": "Manganese-dependent NADPH oxidation by granulocyte particles. The role of superoxide and the nonphysiological nature of the manganese requirement.", "content": "Recent work has indicated that superoxide is involved in the manganese-stimulated oxidation of NADPH by crude granule preparations of guinea pig neutrophils. The characteristics of a model manganese-requiring NADPH-oxidizing system that employs a defined O2-generator have now been compared to the original neutrophil-granule system. With respect to pH dependence, cyanide sensitivity, and reduced pyridine nucleotide specificity, the properties of the two systems are very similar. Additional information has been obtained concerning cation specificity and the kinetics of the metal-catalyzed NADPH oxidation. From the similarities between the properties of the model and neutrophil particle systems, we postulate that the manganese-dependent NADPH oxidation observed in the presence of neutrophil granules represents in large part of nonenzymatic free radical chain involving the oxidation of NADPH to NADP, with O2- as both the chain initiator and one of the propagating species. In this reaction, the neutrophil particles serve only as a source of O2-. Further, the same changes in kinetics (decrease in apparent Km for NADPH) observed previously when granules from phagocytizing rather than resting cells were employed could be mimicked by varying the rate of O2-generation by the model system. We conclude from these results that it is unnecessary to invoke a manganese-requiring enzyme as a component of the phagocytically stimulated respiratory system of the neutrophil.", "contents": "Manganese-dependent NADPH oxidation by granulocyte particles. The role of superoxide and the nonphysiological nature of the manganese requirement. Recent work has indicated that superoxide is involved in the manganese-stimulated oxidation of NADPH by crude granule preparations of guinea pig neutrophils. The characteristics of a model manganese-requiring NADPH-oxidizing system that employs a defined O2-generator have now been compared to the original neutrophil-granule system. With respect to pH dependence, cyanide sensitivity, and reduced pyridine nucleotide specificity, the properties of the two systems are very similar. Additional information has been obtained concerning cation specificity and the kinetics of the metal-catalyzed NADPH oxidation. From the similarities between the properties of the model and neutrophil particle systems, we postulate that the manganese-dependent NADPH oxidation observed in the presence of neutrophil granules represents in large part of nonenzymatic free radical chain involving the oxidation of NADPH to NADP, with O2- as both the chain initiator and one of the propagating species. In this reaction, the neutrophil particles serve only as a source of O2-. Further, the same changes in kinetics (decrease in apparent Km for NADPH) observed previously when granules from phagocytizing rather than resting cells were employed could be mimicked by varying the rate of O2-generation by the model system. We conclude from these results that it is unnecessary to invoke a manganese-requiring enzyme as a component of the phagocytically stimulated respiratory system of the neutrophil."}
{"id": "PMID:7575", "title": "Determinants of lung bacterial clearance in normal mice.", "content": "The determinants of the lung clearance of Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus were studied in normal mice after exposure to an aerosol of viable bacteria and 99mTc-labeled dead bacteria. The fraction of bacteria in lungs that remained viable 4 h after exposure were: S. pneumoniae, 7.3%; K. pneumoniae, 121%; E. coli, 88.5%; S. aureus, 27.6%. The rate of physical removal of bacterial particles (Kmc) was determined from the change in lung 99mTc counts with time: Kmc ranged between 7 and 12%/h and and was similar in all species. The rate of mucociliary clearance and of intrapulmonary bacterial killing (Kk + Kmc) was calculated from the change in bacterial counts with time in animals that had received tetracycline to inhibit bacterial multiplication. Kk, the rate of intrapulmonary killing, was obtained by subtraction of Kmc from (Kk + Kmc). The calculated values for Kk were: S. pneumoniae, - 87%/h; K. pneumoniae, - 17%/h; E. coli, - 18%/h; S. aureus, - 22%/h. The rate of intrapulmonary bacterial multiplication (Kg) was estimated from the relationship of bacterial counts in tetracycline and nontetracycline-treated animals, assuming that tetracycline altered only Kg. Kg, expressed as the doubling time, was: S. pneumoniae, 310 min; K. pneumoniae, 217 min; E.coli, 212 min; S. aureus, infinity (no multiplication). The data indicate that the marked differences in the clearance of these species from the normal mouse lung result from the interaction of differing rates of in vivo bacterial multiplication and killing.", "contents": "Determinants of lung bacterial clearance in normal mice. The determinants of the lung clearance of Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus were studied in normal mice after exposure to an aerosol of viable bacteria and 99mTc-labeled dead bacteria. The fraction of bacteria in lungs that remained viable 4 h after exposure were: S. pneumoniae, 7.3%; K. pneumoniae, 121%; E. coli, 88.5%; S. aureus, 27.6%. The rate of physical removal of bacterial particles (Kmc) was determined from the change in lung 99mTc counts with time: Kmc ranged between 7 and 12%/h and and was similar in all species. The rate of mucociliary clearance and of intrapulmonary bacterial killing (Kk + Kmc) was calculated from the change in bacterial counts with time in animals that had received tetracycline to inhibit bacterial multiplication. Kk, the rate of intrapulmonary killing, was obtained by subtraction of Kmc from (Kk + Kmc). The calculated values for Kk were: S. pneumoniae, - 87%/h; K. pneumoniae, - 17%/h; E. coli, - 18%/h; S. aureus, - 22%/h. The rate of intrapulmonary bacterial multiplication (Kg) was estimated from the relationship of bacterial counts in tetracycline and nontetracycline-treated animals, assuming that tetracycline altered only Kg. Kg, expressed as the doubling time, was: S. pneumoniae, 310 min; K. pneumoniae, 217 min; E.coli, 212 min; S. aureus, infinity (no multiplication). The data indicate that the marked differences in the clearance of these species from the normal mouse lung result from the interaction of differing rates of in vivo bacterial multiplication and killing."}
{"id": "PMID:7576", "title": "Alpha- and beta-adrenergic receptor blocking agents combined with a diuretic in the treatment of essential hypertension.", "content": "The antihypertensive efficacy and side effects of the combined therapy with propranolol, phenoxybenzamine, and hydrochlorothiazide were examined in 17 patients with moderate and moderately severe hypertension. Following a control period two to three weeks' duration, propranolol was started in nine patients as the sole antihypertensive agent and together with phenoxybenzamine, in eight. By titrating the dosage against pulse rate and blood pressure response, propranolol was given, in divided doses, from 80 to 160 mg and phenoxybenzamine, from 20 to 50 mg per day. When propranolol was given alone in nine patients, for four to 12 weeks, normal blood pressure was not attained in any patients. During three to ten weeks of combined propranolol and phenoxybenzamine therapy in 17 patients, normal blood pressure (150/90 mm Hg or less) or near-normal pressure (150/100 or less) was attained in 12 patients in the recumbent position and in 15 patients in the upright position, while orthostatic hypotension was not observed. Except for a reduction of ejaculation in three out of six male patients, no other side effects were encountered. The addition of hydrochlorothiazide diuretic in all of the above 17 patients, at a dose of 50-100 mg per day with a concomitant decrease in the dose of phenoxybenzamine, produced a further reduction in blood pressure, and normal or near-normal blood pressure was attained in all subjects. Symptomatic orthostatic hypotension, observed in two patients, was treated by a further readjustment of the dose of phenoxybenzamine, while inhibition of ejaculation was persistent in only one patient. It is concluded that the combined administration of propranolol, phenoxybenzamine, and hydrochlorothiazide in individualized doses is very effective in lowering the blood pressure with minimal side effects.", "contents": "Alpha- and beta-adrenergic receptor blocking agents combined with a diuretic in the treatment of essential hypertension. The antihypertensive efficacy and side effects of the combined therapy with propranolol, phenoxybenzamine, and hydrochlorothiazide were examined in 17 patients with moderate and moderately severe hypertension. Following a control period two to three weeks' duration, propranolol was started in nine patients as the sole antihypertensive agent and together with phenoxybenzamine, in eight. By titrating the dosage against pulse rate and blood pressure response, propranolol was given, in divided doses, from 80 to 160 mg and phenoxybenzamine, from 20 to 50 mg per day. When propranolol was given alone in nine patients, for four to 12 weeks, normal blood pressure was not attained in any patients. During three to ten weeks of combined propranolol and phenoxybenzamine therapy in 17 patients, normal blood pressure (150/90 mm Hg or less) or near-normal pressure (150/100 or less) was attained in 12 patients in the recumbent position and in 15 patients in the upright position, while orthostatic hypotension was not observed. Except for a reduction of ejaculation in three out of six male patients, no other side effects were encountered. The addition of hydrochlorothiazide diuretic in all of the above 17 patients, at a dose of 50-100 mg per day with a concomitant decrease in the dose of phenoxybenzamine, produced a further reduction in blood pressure, and normal or near-normal blood pressure was attained in all subjects. Symptomatic orthostatic hypotension, observed in two patients, was treated by a further readjustment of the dose of phenoxybenzamine, while inhibition of ejaculation was persistent in only one patient. It is concluded that the combined administration of propranolol, phenoxybenzamine, and hydrochlorothiazide in individualized doses is very effective in lowering the blood pressure with minimal side effects."}
{"id": "PMID:7579", "title": "Milk lipoprotein lipases: a review.", "content": "Lipoprotein lipase activity has been found in the milks from severals species where it is assumed to result from leakage from the mammary gland into milk. The function of the enzyme in the gland is apparently to assist in the transfer of blood lipoprotein triacylglycerol fatty acids into milk triacylglycerols. Bovine skim milk is one of the richest sources of lipoprotein lipase and this enzyme has been purified extensively (7000 fold) by affinity chromatography. The lipase has a molecular weight of about 62000, is inhibited by protamine sulfate, 1.0 M sodium chloride, apolipoprotein C-I (apolipoprotein-serine), and apolipoprotein C-III (apolipoprotein-alanine). The enzyme is activated by apolipoprotein C-II (apolipoprotein-glutamic acid), serum, and by heparin to which it also binds. The lipase is highly specific for the primary esters of acylglycerols and exhibits a slight stereospecificity for the sn-1 ester in preference to the sn-3-ester. Bovine milk also has separate activity toward 1-monoacylglycerols. Human milk contains a serum stimulated lipoprotein lipase with many of the characteristics of the enzyme in bovine milk, as well as an enzyme stimulated by bile salts which resembles the sterol ester hydrolase of rat pancreatic juice. The assay, function, purification, characteristics, and substrate specificities of these enzyme are discussed.", "contents": "Milk lipoprotein lipases: a review. Lipoprotein lipase activity has been found in the milks from severals species where it is assumed to result from leakage from the mammary gland into milk. The function of the enzyme in the gland is apparently to assist in the transfer of blood lipoprotein triacylglycerol fatty acids into milk triacylglycerols. Bovine skim milk is one of the richest sources of lipoprotein lipase and this enzyme has been purified extensively (7000 fold) by affinity chromatography. The lipase has a molecular weight of about 62000, is inhibited by protamine sulfate, 1.0 M sodium chloride, apolipoprotein C-I (apolipoprotein-serine), and apolipoprotein C-III (apolipoprotein-alanine). The enzyme is activated by apolipoprotein C-II (apolipoprotein-glutamic acid), serum, and by heparin to which it also binds. The lipase is highly specific for the primary esters of acylglycerols and exhibits a slight stereospecificity for the sn-1 ester in preference to the sn-3-ester. Bovine milk also has separate activity toward 1-monoacylglycerols. Human milk contains a serum stimulated lipoprotein lipase with many of the characteristics of the enzyme in bovine milk, as well as an enzyme stimulated by bile salts which resembles the sterol ester hydrolase of rat pancreatic juice. The assay, function, purification, characteristics, and substrate specificities of these enzyme are discussed."}
{"id": "PMID:7580", "title": "Synthetic peptides for chymosin and pepsin assays: pH effect and pepsin independent-determination in mixtures.", "content": "Peptide I [H-Phe-Gly-His-Phe(NO2)-Phe-Ala-Phe-OMe] hydrolyzed by chymosin with kcat=.3+/-.3 s-1 and KM=7+/-3 mM (pH 4.7) inhibited competitively peptide II [H-Leu-Ser-Phe(NO2)-Nle-Ala-Leu-OMe] hydrolysis by chymosin with KI=.23 +/- .12 mM at pH 4.7. In reference conditions (.4 mM peptide, .01 M acetate buffer pH 4.7), the specific activities of porcine pepsin and chymosin on peptide I were 470 +/- 70 nM S-1 and .8 nM S-1 per mg of enzyme. This difference in specific activity for peptide I allowed development of a chymosin-independent pepsin assay for mixtures of these enzymes. In addition, peptide II with a specific activity of 2400 +/- 300 nM S-1 and 154 +/- 20 nM S-1 per mg of porcine pepsin and chymosin provides an alternative to measurement of milk clotting for measurement of chymosin- and pepsin-like activities in commercial rennets. Hydrolysis products of peptide II by chymosin exhibited one ionized group of apparent pK of 3.5 +/- .2 and a molar absorption coefficient change of 1000 +/- 100 at pH 4.7 and at 310 nm. From measurements of the kinetic constants, kcat and KM, from pH 2.5 to 7 with peptide II, chymosin activity depends on the protonation of one group of apparent pK 5.3 +/- .2 in the free enzyme. Rennet powder proved to be fairly stable after a 17-month storage at 4 C. Within the same period, a crystalline chymosin solution kept at --18 C lost 30 to 50% of its activity.", "contents": "Synthetic peptides for chymosin and pepsin assays: pH effect and pepsin independent-determination in mixtures. Peptide I [H-Phe-Gly-His-Phe(NO2)-Phe-Ala-Phe-OMe] hydrolyzed by chymosin with kcat=.3+/-.3 s-1 and KM=7+/-3 mM (pH 4.7) inhibited competitively peptide II [H-Leu-Ser-Phe(NO2)-Nle-Ala-Leu-OMe] hydrolysis by chymosin with KI=.23 +/- .12 mM at pH 4.7. In reference conditions (.4 mM peptide, .01 M acetate buffer pH 4.7), the specific activities of porcine pepsin and chymosin on peptide I were 470 +/- 70 nM S-1 and .8 nM S-1 per mg of enzyme. This difference in specific activity for peptide I allowed development of a chymosin-independent pepsin assay for mixtures of these enzymes. In addition, peptide II with a specific activity of 2400 +/- 300 nM S-1 and 154 +/- 20 nM S-1 per mg of porcine pepsin and chymosin provides an alternative to measurement of milk clotting for measurement of chymosin- and pepsin-like activities in commercial rennets. Hydrolysis products of peptide II by chymosin exhibited one ionized group of apparent pK of 3.5 +/- .2 and a molar absorption coefficient change of 1000 +/- 100 at pH 4.7 and at 310 nm. From measurements of the kinetic constants, kcat and KM, from pH 2.5 to 7 with peptide II, chymosin activity depends on the protonation of one group of apparent pK 5.3 +/- .2 in the free enzyme. Rennet powder proved to be fairly stable after a 17-month storage at 4 C. Within the same period, a crystalline chymosin solution kept at --18 C lost 30 to 50% of its activity."}
{"id": "PMID:7581", "title": "Diet calcium and pH versus mineral balance in Holstein cows 84 days pre- to 2 days postpartum.", "content": "Sixteen dry Holstein cows were assigned four groups combining either .2 or 2.1% calcium and pH of either 4.5 or 6.1 in a 2 X 2 factorial arrangement of treatments to study the effect of diet calcium and acidity (pH) on voluntary intake of dry matter, mineral metabolism, and blood constituents. The 86-day experiment was started 84 days prepartum and completed 2 days postpartum. Voluntary dry matter ingestion tended to be higher with higher calcium and acidity (lower pH) diets. Calcium nutriture was improved by more acid diets. More total calcium was apparently absorbed (26 and 7 g) when the diet contained 2.1% calcium, but the .2% calcium diet resulted in a higher apparent percent absorption (25 and 17%) during the dry period. An increased apparent absorption (70 and 5 g) and utilization of diet calcium occurred with the higher calcium treatment at 2 days postpartum. Magnesium and phosphorus utilizations were improved with lower diet calcium. Although experimental treatments had no significant effect on blood minerals, serum calcium decreased 12% 2 days postpartum. A better calcium nutriture was provided by the higher calcium diets when the diets maintained a positive balance for magnesium and phosphorus.", "contents": "Diet calcium and pH versus mineral balance in Holstein cows 84 days pre- to 2 days postpartum. Sixteen dry Holstein cows were assigned four groups combining either .2 or 2.1% calcium and pH of either 4.5 or 6.1 in a 2 X 2 factorial arrangement of treatments to study the effect of diet calcium and acidity (pH) on voluntary intake of dry matter, mineral metabolism, and blood constituents. The 86-day experiment was started 84 days prepartum and completed 2 days postpartum. Voluntary dry matter ingestion tended to be higher with higher calcium and acidity (lower pH) diets. Calcium nutriture was improved by more acid diets. More total calcium was apparently absorbed (26 and 7 g) when the diet contained 2.1% calcium, but the .2% calcium diet resulted in a higher apparent percent absorption (25 and 17%) during the dry period. An increased apparent absorption (70 and 5 g) and utilization of diet calcium occurred with the higher calcium treatment at 2 days postpartum. Magnesium and phosphorus utilizations were improved with lower diet calcium. Although experimental treatments had no significant effect on blood minerals, serum calcium decreased 12% 2 days postpartum. A better calcium nutriture was provided by the higher calcium diets when the diets maintained a positive balance for magnesium and phosphorus."}
{"id": "PMID:7583", "title": "The role of precipitins and complement activation in the etiology of allergic lung disease.", "content": "An experimental model of allergic lung disease has been described that is monitored by analysis of arterial oxygen tension following aerosol challenge with antigen. Rabbits immunized to a classical soluble antigen, human serum albumin (HSA), to the point where severe Arthus skin reactivity was demonstrable, were aerosol-challenged with antigen. Arterial oxygen tension measurements made on pre- and post-challenge samples yielded early, late, and continuous response patterns, reminiscent of those obtained in humans following provocation testing. Aerosol challenge of unimmunized animals with HSA resulted in no change from baseline conditions. Unimmunized rabbits exposed to small and massive (10X) aerosols of Aspergillus spores also demonstrated various postchallenge depressions in arterial oxygen tension as well as decreased levels in hemolytic complement activity, depending on the species of fungus and dose of spores used. Unimmunized animals pretreated with cobra venom factor in a manner known to achieve complement depletion failed to respond with altered arterial oxygen tensions following similar aerosol challenge. It is postulated that although precipitins may play a role in artificial disease initiated by soluble antigens, nonspecific complement activation may be more important in understanding the etiology of spontaneous disease in humans brought about by inhalation of moldy particulate matter.", "contents": "The role of precipitins and complement activation in the etiology of allergic lung disease. An experimental model of allergic lung disease has been described that is monitored by analysis of arterial oxygen tension following aerosol challenge with antigen. Rabbits immunized to a classical soluble antigen, human serum albumin (HSA), to the point where severe Arthus skin reactivity was demonstrable, were aerosol-challenged with antigen. Arterial oxygen tension measurements made on pre- and post-challenge samples yielded early, late, and continuous response patterns, reminiscent of those obtained in humans following provocation testing. Aerosol challenge of unimmunized animals with HSA resulted in no change from baseline conditions. Unimmunized rabbits exposed to small and massive (10X) aerosols of Aspergillus spores also demonstrated various postchallenge depressions in arterial oxygen tension as well as decreased levels in hemolytic complement activity, depending on the species of fungus and dose of spores used. Unimmunized animals pretreated with cobra venom factor in a manner known to achieve complement depletion failed to respond with altered arterial oxygen tensions following similar aerosol challenge. It is postulated that although precipitins may play a role in artificial disease initiated by soluble antigens, nonspecific complement activation may be more important in understanding the etiology of spontaneous disease in humans brought about by inhalation of moldy particulate matter."}
{"id": "PMID:7584", "title": "The effect of pertussis and beta adrenergic-blocking agents on mast cells.", "content": "Pertussis vaccine injected ip in doses known to cause hypersensitization resulted in a marked decrease in the number of mast cells from the peritoneal washings of rats and mice. A significant reduction was obtained as early as one day after pertussis injection of ten billion cells in rats and was marked after 5 to 7 days. A maximum reduction in the number of mast cells was obtained by a dose of 20 billion cells. There was no detectable histamine biological activity in the supernatant from peritoneal washings obtained after 10 min, 60 min, and 24 hr from control and pertussis-treated rats, indicating that pertussis did not cause degranulation of mast cells in vivo. The histamine content in the precipitated mast cell pellets from control rats was much higher than the corresponding histamine content from pertussis-treated rats. In rats and mice, propranolol and other beta adrenergic-blocking agents caused degranulation of mast cells in the peritoneal washings in vitro. Practolol was the least effective beta adrenergic-blocking agent in degranulating mast cells. Catecholamines, histamine, 6-hydroxydopamine, methacholine, and pertussis failed to cause any degranulation. Isoproterenol protected the mast cell against the degranulation induced by propranolol. Propranolol caused bluing in rat and mice skin when injected id. Mast cells from control and pertussis-injected rats were equally sensitive to propranolol in vitro. The low recovery of mast cells from the peritoneal washings of rats and mice is thought to be due to mobilization of mast cells away from the peritoneum.", "contents": "The effect of pertussis and beta adrenergic-blocking agents on mast cells. Pertussis vaccine injected ip in doses known to cause hypersensitization resulted in a marked decrease in the number of mast cells from the peritoneal washings of rats and mice. A significant reduction was obtained as early as one day after pertussis injection of ten billion cells in rats and was marked after 5 to 7 days. A maximum reduction in the number of mast cells was obtained by a dose of 20 billion cells. There was no detectable histamine biological activity in the supernatant from peritoneal washings obtained after 10 min, 60 min, and 24 hr from control and pertussis-treated rats, indicating that pertussis did not cause degranulation of mast cells in vivo. The histamine content in the precipitated mast cell pellets from control rats was much higher than the corresponding histamine content from pertussis-treated rats. In rats and mice, propranolol and other beta adrenergic-blocking agents caused degranulation of mast cells in the peritoneal washings in vitro. Practolol was the least effective beta adrenergic-blocking agent in degranulating mast cells. Catecholamines, histamine, 6-hydroxydopamine, methacholine, and pertussis failed to cause any degranulation. Isoproterenol protected the mast cell against the degranulation induced by propranolol. Propranolol caused bluing in rat and mice skin when injected id. Mast cells from control and pertussis-injected rats were equally sensitive to propranolol in vitro. The low recovery of mast cells from the peritoneal washings of rats and mice is thought to be due to mobilization of mast cells away from the peritoneum."}
{"id": "PMID:7585", "title": "Disodium cromoglycate in ragweed-allergic rhinitis.", "content": "This study was designed to test the effectiveness of disodium cromoglycate when compared to placebo in a double-blind study in patients with ragweed allergic rhinitis. Patients were selected on the basis of a clinical history and a 4+ reaction to the intradermal injection of water-soluble ragweed, 0.02 c.c. of 500 PNU/c.c. Active agent/placebo groups were selected at random and were on the drug for approximately 8 wk, commencing 1 wk prior to the onset of the ragweed pollen season. Patient response was evaluated using patient diary cards, number of antihistamine tablets taken, and patient interviews. In the Toronto study, of 17 patients on the active drug, 15 were graded as improved, compared to only 6 of 21 placebo-treated patients who were improved. However, in the Hamilton study, results were less impressive. Nonetheless, it appears that intranasal insufflation of disodium cromoglycate was more effective in reducing ragweed hay fever symptoms than placebo.", "contents": "Disodium cromoglycate in ragweed-allergic rhinitis. This study was designed to test the effectiveness of disodium cromoglycate when compared to placebo in a double-blind study in patients with ragweed allergic rhinitis. Patients were selected on the basis of a clinical history and a 4+ reaction to the intradermal injection of water-soluble ragweed, 0.02 c.c. of 500 PNU/c.c. Active agent/placebo groups were selected at random and were on the drug for approximately 8 wk, commencing 1 wk prior to the onset of the ragweed pollen season. Patient response was evaluated using patient diary cards, number of antihistamine tablets taken, and patient interviews. In the Toronto study, of 17 patients on the active drug, 15 were graded as improved, compared to only 6 of 21 placebo-treated patients who were improved. However, in the Hamilton study, results were less impressive. Nonetheless, it appears that intranasal insufflation of disodium cromoglycate was more effective in reducing ragweed hay fever symptoms than placebo."}
{"id": "PMID:7588", "title": "Piperacetazine versus thioridazine in the treatment of organic brain disease: a controlled double-blind study.", "content": "In a double-blind cross-over study, 50 geriatric patients with organic brain disease were divided into two groups. One group first received piperacetazine for 15 days and then thioridazine for 15 days. For the other group the sequence was reversed. Piperacetazine proved to be at least as effective as thioridazine and seemed to be more effective against certain target symptoms; side effects were less common and less severe.", "contents": "Piperacetazine versus thioridazine in the treatment of organic brain disease: a controlled double-blind study. In a double-blind cross-over study, 50 geriatric patients with organic brain disease were divided into two groups. One group first received piperacetazine for 15 days and then thioridazine for 15 days. For the other group the sequence was reversed. Piperacetazine proved to be at least as effective as thioridazine and seemed to be more effective against certain target symptoms; side effects were less common and less severe."}
{"id": "PMID:7629", "title": "Duodenal immunoglobulin deficiency in graft versus host disease (GVHD) mice.", "content": "The small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfuction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal. should be investigated. GVHD was produced in newborn BLA (C57 BL/Ka females x BALB-C males) mice house in a specific pathogen-free environment by the i.p. inoculation of 10(7) male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls. A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined.", "contents": "Duodenal immunoglobulin deficiency in graft versus host disease (GVHD) mice. The small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfuction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal. should be investigated. GVHD was produced in newborn BLA (C57 BL/Ka females x BALB-C males) mice house in a specific pathogen-free environment by the i.p. inoculation of 10(7) male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls. A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined."}
{"id": "PMID:7630", "title": "Partial regain of activity in heterologous recombinants of phosphorylcholine-binding M-components from different species.", "content": "Recombination experiments were performed with heavy and light chains derived from a Waldenstr\u00f6m's IgM with specificity against phosphorylcholine. The recombinant molecules had an association constant for phosphorylcholine in the same order of magnitude as the native IgM; the number of binding sites at saturation was only slightly decreased in the reconstituted molecules, indicating regain of binding activity after recombination of IgM heavy and light chains. Heterologous recombinants obtained with polypeptide chains of another monoclonal IgM without demonstrable binding activity recovered only 5 to 10% of the binding activity of homologous recombinants. Hybrid molecules prepared with heavy and light chains from the phosphorylcholine-binding mouse IgA myeloma protein TEPC-15, however, regained as much as 41% of the binding activity of the homologous recombinants; these data suggest a considerable degree of structural homology shared by the human IgM and the murine IgA proteins with phosphorylcholine-binding specifity.", "contents": "Partial regain of activity in heterologous recombinants of phosphorylcholine-binding M-components from different species. Recombination experiments were performed with heavy and light chains derived from a Waldenstr\u00f6m's IgM with specificity against phosphorylcholine. The recombinant molecules had an association constant for phosphorylcholine in the same order of magnitude as the native IgM; the number of binding sites at saturation was only slightly decreased in the reconstituted molecules, indicating regain of binding activity after recombination of IgM heavy and light chains. Heterologous recombinants obtained with polypeptide chains of another monoclonal IgM without demonstrable binding activity recovered only 5 to 10% of the binding activity of homologous recombinants. Hybrid molecules prepared with heavy and light chains from the phosphorylcholine-binding mouse IgA myeloma protein TEPC-15, however, regained as much as 41% of the binding activity of the homologous recombinants; these data suggest a considerable degree of structural homology shared by the human IgM and the murine IgA proteins with phosphorylcholine-binding specifity."}
{"id": "PMID:7631", "title": "Neonatal infection with mouse thymic virus. Differential effects on T cells mediating the graft-versus-host reaction.", "content": "Neonatal infection with mouse thymic virus (TA), a murine herpes virus, produced extensive but temporary necrosis of the thymus which was maximal at 10 to 14 days of age. Studies of precursor and amplifier cells mediating graft-vs-host (GVH) reactivity of thymocytes, spleen cells (SC), and lymph node cells (LNC) of normal and TA-infected mice were made at 4 and 8 weeks of age. Infection with TA resulting in a profound reduction (70 to 80%) in the direct GVH reactivity of thymocytes at both ages; by comparison, the capacity of thymocytes to produce synergy when combined with normal LNC was normal at 8 weeks. Direct GVH reactivity of SC was depressed 90% 4 weeks after infection with TA but returned to near normal at 8 weeks. Direct GVH reactivity of LNC from TA-infected mice was normal at 4 and 8 weeks of age, but amplifier T cell activity in LNC was markedly depressed at 8 wekks. These results demonstrate that TA has highly selective effects upon subpopulations of T cells in thymus and lymph node.", "contents": "Neonatal infection with mouse thymic virus. Differential effects on T cells mediating the graft-versus-host reaction. Neonatal infection with mouse thymic virus (TA), a murine herpes virus, produced extensive but temporary necrosis of the thymus which was maximal at 10 to 14 days of age. Studies of precursor and amplifier cells mediating graft-vs-host (GVH) reactivity of thymocytes, spleen cells (SC), and lymph node cells (LNC) of normal and TA-infected mice were made at 4 and 8 weeks of age. Infection with TA resulting in a profound reduction (70 to 80%) in the direct GVH reactivity of thymocytes at both ages; by comparison, the capacity of thymocytes to produce synergy when combined with normal LNC was normal at 8 weeks. Direct GVH reactivity of SC was depressed 90% 4 weeks after infection with TA but returned to near normal at 8 weeks. Direct GVH reactivity of LNC from TA-infected mice was normal at 4 and 8 weeks of age, but amplifier T cell activity in LNC was markedly depressed at 8 wekks. These results demonstrate that TA has highly selective effects upon subpopulations of T cells in thymus and lymph node."}
{"id": "PMID:7589", "title": "[Voluntary choice of sex. The present state of our knowledge].", "content": "Whether we like it or not, the next demand that the modern couple will make after birth control will be voluntary selection of the sex of their babies. Furthermore, this selection does have an undoubted medical value in preventing certain sex-linked congenital or hereditary diseases. Many research workers have turned their attention to these problems over the past years, especially in the U.S.A., in England and in Germany. After a historical review of the progress that has taken place in this area a study has been undertaken into the actual state of research in the U.S.A. and in Germany, in which the country the Federal Government has created a special department for scientific research. Our present knowledge into the methods that are adopted to obtain a foetus of male of female sex up to the present is then briefly explained. The results obtained by the principle research workers have been summarised. These are between 80 and 90 per cent success. The steps that have marked these discoveries in this field that is ill understood by the majority of doctors and the French public are outlined.", "contents": "[Voluntary choice of sex. The present state of our knowledge]. Whether we like it or not, the next demand that the modern couple will make after birth control will be voluntary selection of the sex of their babies. Furthermore, this selection does have an undoubted medical value in preventing certain sex-linked congenital or hereditary diseases. Many research workers have turned their attention to these problems over the past years, especially in the U.S.A., in England and in Germany. After a historical review of the progress that has taken place in this area a study has been undertaken into the actual state of research in the U.S.A. and in Germany, in which the country the Federal Government has created a special department for scientific research. Our present knowledge into the methods that are adopted to obtain a foetus of male of female sex up to the present is then briefly explained. The results obtained by the principle research workers have been summarised. These are between 80 and 90 per cent success. The steps that have marked these discoveries in this field that is ill understood by the majority of doctors and the French public are outlined."}
{"id": "PMID:7632", "title": "Affinity chromatography of lipase with hydrophobic ligands coupled to cyanogen bromide-activated agarose.", "content": "The behavior of lipase produced by Pseudomans mephitica var. lipopytica toward hydrophobic residues coupled to spacer gels that were prepared by coupling a primary amine to CNBr-activated agarose, was studied. The lipase adsorbed on the ligand of a long unbranched aliphatic chain, a benzene ring, or deoxycholic acid was only slightly or not all eluted at pH 5 or pH 11 by buffers containing 1 M NcC1. The lipase was eluted by liquid containing a surfactant or an organic solvent miscible with water, indicating greater involvement of hydrophobic forces. The adsorption of propane, cyclopentane, cyclohexane, cycloheptane, or chrysene appears to be achieved through electrostatic forces, inasmuch as desorption was caused by buffer containing 1 M NaC1 at pH 11. The amount of lipase adsorbed on these hydrophobic ligands was about the same as that adsorbed on the ligands belonging to the first group. Since little lipase wad adsorbed on cyclopropane, cycloctane, pyridine, methane, n-pentane, or branched aliphatic chains, these ligands appear to impose steric hindrance on the adsorption of lipase, or they may be too small to fit into the hydrophobic sites of lipase.", "contents": "Affinity chromatography of lipase with hydrophobic ligands coupled to cyanogen bromide-activated agarose. The behavior of lipase produced by Pseudomans mephitica var. lipopytica toward hydrophobic residues coupled to spacer gels that were prepared by coupling a primary amine to CNBr-activated agarose, was studied. The lipase adsorbed on the ligand of a long unbranched aliphatic chain, a benzene ring, or deoxycholic acid was only slightly or not all eluted at pH 5 or pH 11 by buffers containing 1 M NcC1. The lipase was eluted by liquid containing a surfactant or an organic solvent miscible with water, indicating greater involvement of hydrophobic forces. The adsorption of propane, cyclopentane, cyclohexane, cycloheptane, or chrysene appears to be achieved through electrostatic forces, inasmuch as desorption was caused by buffer containing 1 M NaC1 at pH 11. The amount of lipase adsorbed on these hydrophobic ligands was about the same as that adsorbed on the ligands belonging to the first group. Since little lipase wad adsorbed on cyclopropane, cycloctane, pyridine, methane, n-pentane, or branched aliphatic chains, these ligands appear to impose steric hindrance on the adsorption of lipase, or they may be too small to fit into the hydrophobic sites of lipase."}
{"id": "PMID:7633", "title": "Urticaria.", "content": "Urticaria is a problem often as vexing to the physician as to the patient. The approach to the patient with hives first demands a search for the etiology, whether endogenous and triggered by emotions or occult systemic disease, exogenous and triggered by allergy to inhaled or ingested antigens, or physical and due to abnormal sensitivity to heat, cold, light, or pressure. Often a fruitless search, the diagnostic evaluation must be accompanied by appropriate symptomatic therapy requiring familiarity with the antihistamines and their relative advantages in the various forms of urticaria. Elimination diets are of diagnostic as well as therapeutic value: pencillin-free, yeast-free, and salicylate-free diets are particularly useful. Therapeutic trials of tetracycline, nystatin and griseofulvin may be helpful, while corticosteroids and specific desensitization are rarely of value.", "contents": "Urticaria. Urticaria is a problem often as vexing to the physician as to the patient. The approach to the patient with hives first demands a search for the etiology, whether endogenous and triggered by emotions or occult systemic disease, exogenous and triggered by allergy to inhaled or ingested antigens, or physical and due to abnormal sensitivity to heat, cold, light, or pressure. Often a fruitless search, the diagnostic evaluation must be accompanied by appropriate symptomatic therapy requiring familiarity with the antihistamines and their relative advantages in the various forms of urticaria. Elimination diets are of diagnostic as well as therapeutic value: pencillin-free, yeast-free, and salicylate-free diets are particularly useful. Therapeutic trials of tetracycline, nystatin and griseofulvin may be helpful, while corticosteroids and specific desensitization are rarely of value."}
{"id": "PMID:7635", "title": "Effect of amiloride and some of its analogues of cation transport in isolated frog skin and thin lipid membranes.", "content": "The inhibition of short-circuit current (Isc) in isolated frog skin and the induction of surface potentials in lipid bilayer membranes produced by the diuretic drug amiloride and a number of its chemical analogues was studied. The major conclusions of our study are: (a) The charged form of amiloride is the biologically active species. (b) Both the magnitude of Isc and the amiloride inhibitory effect are sensitive to the ionic milieu bathing the isolated skin, and these two features are modulated at separate and distinct regions on the transport site. (c) Amiloride is very specific in its inhibitory interaction with the Na+ transport site since slight structural modifications can result in significant changes in drug effectiveness. We found that substitutions at pyrazine ring position 5 greatly diminish drug activity, while changes at position 6 are less drastic. Alterations in the guanidinium moiety only diminish activity if the result is a change in the spatial orientation of the amino group carrying the positive charge. (d) Amiloride can bind to and alter the charge on membrane surfaces, but this action cannot explain its highly specific effects in biological systems.", "contents": "Effect of amiloride and some of its analogues of cation transport in isolated frog skin and thin lipid membranes. The inhibition of short-circuit current (Isc) in isolated frog skin and the induction of surface potentials in lipid bilayer membranes produced by the diuretic drug amiloride and a number of its chemical analogues was studied. The major conclusions of our study are: (a) The charged form of amiloride is the biologically active species. (b) Both the magnitude of Isc and the amiloride inhibitory effect are sensitive to the ionic milieu bathing the isolated skin, and these two features are modulated at separate and distinct regions on the transport site. (c) Amiloride is very specific in its inhibitory interaction with the Na+ transport site since slight structural modifications can result in significant changes in drug effectiveness. We found that substitutions at pyrazine ring position 5 greatly diminish drug activity, while changes at position 6 are less drastic. Alterations in the guanidinium moiety only diminish activity if the result is a change in the spatial orientation of the amino group carrying the positive charge. (d) Amiloride can bind to and alter the charge on membrane surfaces, but this action cannot explain its highly specific effects in biological systems."}
{"id": "PMID:7636", "title": "Studies on the rumen flagellate Sphaeromonas communis.", "content": "The rumen flagellate Sphaeromonas communis showed a significant increase in population density 1 to 2 h after the host sheep commenced feeding, followed by a reduction in numbers to the pre-feeding level after a further 2 to 3 h. The life-history of the organism was shown to consist of a motile flagellate which germinated to produce a vegetative stage comprising a limited rhizoidal system on which up to three reproductive bodies were borne together with (in vitro) other spherical bodies of unknown function; in vivo, the reproductive bodies were stimulated to liberate flagellates by a component of the diet of the host. The vegetative stage strongly resembled that of certain species of aquatic phycomycete fungi, and the flagellates may therefore by zoospores. Flagellates liberated in vivo lost their motility within 2 to 3 h and developed into the reproductive vegetative phase, producing a rapid decrease in numbers of flagellates. Conditions of maximum flagellate production (pH 6.5, 39 degrees C, presence of CO2, absnece of oxygen) approximated to those found in the rumen. The organism was cultured in vitro in an undefined medium in the absnece of bacteria and other flagellates.", "contents": "Studies on the rumen flagellate Sphaeromonas communis. The rumen flagellate Sphaeromonas communis showed a significant increase in population density 1 to 2 h after the host sheep commenced feeding, followed by a reduction in numbers to the pre-feeding level after a further 2 to 3 h. The life-history of the organism was shown to consist of a motile flagellate which germinated to produce a vegetative stage comprising a limited rhizoidal system on which up to three reproductive bodies were borne together with (in vitro) other spherical bodies of unknown function; in vivo, the reproductive bodies were stimulated to liberate flagellates by a component of the diet of the host. The vegetative stage strongly resembled that of certain species of aquatic phycomycete fungi, and the flagellates may therefore by zoospores. Flagellates liberated in vivo lost their motility within 2 to 3 h and developed into the reproductive vegetative phase, producing a rapid decrease in numbers of flagellates. Conditions of maximum flagellate production (pH 6.5, 39 degrees C, presence of CO2, absnece of oxygen) approximated to those found in the rumen. The organism was cultured in vitro in an undefined medium in the absnece of bacteria and other flagellates."}
{"id": "PMID:7637", "title": "Influence of dilution rate on NAD(P) and NAD(P)H concentrations and ratios in a Pseudomonas sp. grown in continuous culture.", "content": "A freshwater Pseudomonas sp. was grown in continuous culture under steady-state conditions in L-lactate-, succinate-, glucose- or ammonium-limited media. Under carbon limitation, the NAD(H) (i.e. NAD + NADH) concentration of the organisms increased exponentially from approximately 2 to 7 mumol/g dry wt as the culture dilution rate (D) was decreased from 0.5 to 0.02 h-1. Organisms grown at a given D in any of the carbon-limited media possessed very similar levels of NAD(H). Therefore, under these conditions, cellular NAD(H) was only a function of the culture O and was independent of the nature of the culture carbon source. D had no influence on the NAD(H) content of cells grown under ammonium limitation. In contrast, cellular NADH concentration was not influenced by D in carbon- or ammonium-limited media. In L-lactate-limited medium, bacteria possessed 0.14 mumol NADH/g dry wt; very similar levels were found in organisms grown in the other media. The results are consistent with those of Wimpenny & Firth (1972) that bacteria rigidly maintain a constant NADH level rather than a constant constant NADH: NAD ratio. NADP(H) (i.e. NADP + NADPH) and NADPH levels were also not influenced by changes in the culture carbon source or in D; in L-lactate-limited medium these concentrations were 0.97 and 0.53 mumol/g cell dry wt, respectively. The NADPH:NADP(H) ratio was much higher than the NADH:NAD(H) ratio, averaging 55% in carbon-limited cells.", "contents": "Influence of dilution rate on NAD(P) and NAD(P)H concentrations and ratios in a Pseudomonas sp. grown in continuous culture. A freshwater Pseudomonas sp. was grown in continuous culture under steady-state conditions in L-lactate-, succinate-, glucose- or ammonium-limited media. Under carbon limitation, the NAD(H) (i.e. NAD + NADH) concentration of the organisms increased exponentially from approximately 2 to 7 mumol/g dry wt as the culture dilution rate (D) was decreased from 0.5 to 0.02 h-1. Organisms grown at a given D in any of the carbon-limited media possessed very similar levels of NAD(H). Therefore, under these conditions, cellular NAD(H) was only a function of the culture O and was independent of the nature of the culture carbon source. D had no influence on the NAD(H) content of cells grown under ammonium limitation. In contrast, cellular NADH concentration was not influenced by D in carbon- or ammonium-limited media. In L-lactate-limited medium, bacteria possessed 0.14 mumol NADH/g dry wt; very similar levels were found in organisms grown in the other media. The results are consistent with those of Wimpenny & Firth (1972) that bacteria rigidly maintain a constant NADH level rather than a constant constant NADH: NAD ratio. NADP(H) (i.e. NADP + NADPH) and NADPH levels were also not influenced by changes in the culture carbon source or in D; in L-lactate-limited medium these concentrations were 0.97 and 0.53 mumol/g cell dry wt, respectively. The NADPH:NADP(H) ratio was much higher than the NADH:NAD(H) ratio, averaging 55% in carbon-limited cells."}
{"id": "PMID:7642", "title": "Differences between the anorexic actions of amphetamine and fenfluramine--possible effects on hunger and satiety.", "content": "The inhition of feeding in rats brought about by amphetamine and fenfluramine was continuously monitored for periods of up to 24 h using a pellet detecting eatometer. For rats tested under conditions of food deprivation the two drugs gave rise to distinctive anorexic profiles: amphetamine delayed the onset of eating whereas fenfluramine allowed eating to commence normally but brought about an early termination of the initial bout of feeding. When the drugs were administrated to rats with free access to food, analysis of the meal pattern showed that amphetamine gave rise to a small increase in the inter-meal interval while fenfluramine brought about a clear reduction tion in meal size. It is suggested that the contrasting modes of action of these drugs represent an effect of amphetamine upon hunger and an action of fenfluramine on satiety. This suggestion is in keeping with the proposed mechanisms of action of these drugs, amphetamine acting upon a hpothalamic motivational system and fenfluramine acting by means of a postulated serotoninergic satiety system. Use of the continuous monitoring technique has pointed pointed to certain limitations in the assessment of anorexic drug action by means of discrete food sampling periods.", "contents": "Differences between the anorexic actions of amphetamine and fenfluramine--possible effects on hunger and satiety. The inhition of feeding in rats brought about by amphetamine and fenfluramine was continuously monitored for periods of up to 24 h using a pellet detecting eatometer. For rats tested under conditions of food deprivation the two drugs gave rise to distinctive anorexic profiles: amphetamine delayed the onset of eating whereas fenfluramine allowed eating to commence normally but brought about an early termination of the initial bout of feeding. When the drugs were administrated to rats with free access to food, analysis of the meal pattern showed that amphetamine gave rise to a small increase in the inter-meal interval while fenfluramine brought about a clear reduction tion in meal size. It is suggested that the contrasting modes of action of these drugs represent an effect of amphetamine upon hunger and an action of fenfluramine on satiety. This suggestion is in keeping with the proposed mechanisms of action of these drugs, amphetamine acting upon a hpothalamic motivational system and fenfluramine acting by means of a postulated serotoninergic satiety system. Use of the continuous monitoring technique has pointed pointed to certain limitations in the assessment of anorexic drug action by means of discrete food sampling periods."}
{"id": "PMID:7643", "title": "Alpha-methyl derivatives of biogenic amines as inhibitors of monoamin oxidase.", "content": "The values of Km app and Vmax for three natural substrates of monoamine oxidase have been determined at various stages in the isolation of the enzyme from rat liver tissue. The results are consistent with the presence in the enzyme preparation of at least two distinct molecular forms of the enzyme. Using the alpha-methyl derivatives of the natural substrates as inhibitors of the enzyme, the substrate dependence of Ki further substantiates this view. In addition, the kinetics of the inhibition suggest that the value of Km app may not for all substrates, necessarily be a measure of the affinity of the substrate for the enzyme.", "contents": "Alpha-methyl derivatives of biogenic amines as inhibitors of monoamin oxidase. The values of Km app and Vmax for three natural substrates of monoamine oxidase have been determined at various stages in the isolation of the enzyme from rat liver tissue. The results are consistent with the presence in the enzyme preparation of at least two distinct molecular forms of the enzyme. Using the alpha-methyl derivatives of the natural substrates as inhibitors of the enzyme, the substrate dependence of Ki further substantiates this view. In addition, the kinetics of the inhibition suggest that the value of Km app may not for all substrates, necessarily be a measure of the affinity of the substrate for the enzyme."}
{"id": "PMID:7644", "title": "Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes.", "content": "The effects of mianserin, a tetracyclic antidepressant, on uptake and release of [3H]noradrenaline (3H-NA), [3H]dopamine (3H-DA), [3H]-5-hydroxytryptamine(3H-5-HT) and [3H]gamma-amino-butyric acid (3H-GABA) in synaptosomes from different areas of the rat brain were investigated in a comparative study with the tricyclic antidepressant imipramine. Mianserin and imipramine were inhibitors of 3H-NA uptake in the hypothalamus, but could not increase 3H-NA release from noradrenergic nerve endings. This behaviour was similar to that of (+)-amphetamine. Both mianserin and imipramine had essentially no effect on 3H-DA transport mechanisms in striatal synaptosomes. (+)-Amphetamine, in contrast, strongly affected both 3H-DA uptake and release. Imipramine was stronger than mianserin in inhibiting 3H-5-HT accumulation by striatal synaptosomes. In contrast, mianserin stimulated 3H-5-HT release whereas imipramine was ineffective. Mianserin had virtually no inhibitory activity on 3H-5-HT uptake by rat blood platelets. Imipramine was a modest inhibitor of 3H-GABA accumulation by whole brain synaptosomes; mianserin had no effect. Both drugs did not alter 3H-GABA release. These results indicate that mianserin interferes in a way different from that to tricyclic antidepressants with the neurotransmitter transport mechanisms at the presynaptic level.", "contents": "Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes. The effects of mianserin, a tetracyclic antidepressant, on uptake and release of [3H]noradrenaline (3H-NA), [3H]dopamine (3H-DA), [3H]-5-hydroxytryptamine(3H-5-HT) and [3H]gamma-amino-butyric acid (3H-GABA) in synaptosomes from different areas of the rat brain were investigated in a comparative study with the tricyclic antidepressant imipramine. Mianserin and imipramine were inhibitors of 3H-NA uptake in the hypothalamus, but could not increase 3H-NA release from noradrenergic nerve endings. This behaviour was similar to that of (+)-amphetamine. Both mianserin and imipramine had essentially no effect on 3H-DA transport mechanisms in striatal synaptosomes. (+)-Amphetamine, in contrast, strongly affected both 3H-DA uptake and release. Imipramine was stronger than mianserin in inhibiting 3H-5-HT accumulation by striatal synaptosomes. In contrast, mianserin stimulated 3H-5-HT release whereas imipramine was ineffective. Mianserin had virtually no inhibitory activity on 3H-5-HT uptake by rat blood platelets. Imipramine was a modest inhibitor of 3H-GABA accumulation by whole brain synaptosomes; mianserin had no effect. Both drugs did not alter 3H-GABA release. These results indicate that mianserin interferes in a way different from that to tricyclic antidepressants with the neurotransmitter transport mechanisms at the presynaptic level."}
{"id": "PMID:7645", "title": "Adrenergic responses of the rabbit stomach serosal strip and their modification by monoamine oxidase inhibitors and anti-adrenergic drugs.", "content": "The rabbit stomach serosal strip, was found to contract to adrenaline and noradrenaline but not to isoprenaline. The contractile response could be totally abolished by phenoxybenzamine but was not influenced by propranolol, indicating that the preparation has almost exclusively alpha-adrenoceptors. The responses to adrenaline and noradrenaline were markedly potentiated in the presence of monoamine oxidase inhibitors, guanethidine or reserpine, indicating the presence of MAO activity in the tissue and possible catecholamine stores. The functional state of the latter has not been conclusively established, since tyramine, an indirectly acting amine, was unable to elicit a response qualitatively similar to that of adrenaline, even in the presence of nialamide or tranylcypromine.", "contents": "Adrenergic responses of the rabbit stomach serosal strip and their modification by monoamine oxidase inhibitors and anti-adrenergic drugs. The rabbit stomach serosal strip, was found to contract to adrenaline and noradrenaline but not to isoprenaline. The contractile response could be totally abolished by phenoxybenzamine but was not influenced by propranolol, indicating that the preparation has almost exclusively alpha-adrenoceptors. The responses to adrenaline and noradrenaline were markedly potentiated in the presence of monoamine oxidase inhibitors, guanethidine or reserpine, indicating the presence of MAO activity in the tissue and possible catecholamine stores. The functional state of the latter has not been conclusively established, since tyramine, an indirectly acting amine, was unable to elicit a response qualitatively similar to that of adrenaline, even in the presence of nialamide or tranylcypromine."}
{"id": "PMID:7646", "title": "The absorption of warfarin from the rat small intestine in situ.", "content": "The in situ absorption from the rat small intestine of the weakly acidic drug, warfarin (pKa 5-05), at 200 mug ml-1 in the instilled fluid with initial pH levels of 3, 5, 7 or 8 has been examined. These initial pH's in the buffer changed rapidly towards neutrality. The buffers at pH's 3 and 5 probably caused different amounts of warfarin precipitation, which resulted in different rates of warfarin disappearance from the instilled fluid which paralleled the initial rates of accumulation of warfarin in (or on) the intestinal wall. Where greater drug precipitation had probably occurred the initial rates of absorption into the plasma were slower. At the initial pH of 3 and by solubilization of warfarin with propylene glycol, the rate of absorption was similar to that from a fluid of pH 7. Propylene glycol in 15% solution did not affect the system significantly. The relatively high transfer of warfarin into octanol from buffer solution at pH 7 might indicate that the small fraction of unionized drug (1 : 100) at pH 7 is enough for remarkable transfer of this highly lipid-soluble drug.", "contents": "The absorption of warfarin from the rat small intestine in situ. The in situ absorption from the rat small intestine of the weakly acidic drug, warfarin (pKa 5-05), at 200 mug ml-1 in the instilled fluid with initial pH levels of 3, 5, 7 or 8 has been examined. These initial pH's in the buffer changed rapidly towards neutrality. The buffers at pH's 3 and 5 probably caused different amounts of warfarin precipitation, which resulted in different rates of warfarin disappearance from the instilled fluid which paralleled the initial rates of accumulation of warfarin in (or on) the intestinal wall. Where greater drug precipitation had probably occurred the initial rates of absorption into the plasma were slower. At the initial pH of 3 and by solubilization of warfarin with propylene glycol, the rate of absorption was similar to that from a fluid of pH 7. Propylene glycol in 15% solution did not affect the system significantly. The relatively high transfer of warfarin into octanol from buffer solution at pH 7 might indicate that the small fraction of unionized drug (1 : 100) at pH 7 is enough for remarkable transfer of this highly lipid-soluble drug."}
{"id": "PMID:7647", "title": "The influence of dihydroxyanthracene derivatives on water and electrolyte movement in rat colon.", "content": "The purgative activities of 18 different dihydroxyanthracene derivatives, including free anthraquinones and anthrones, were investigated by determining their influence on the water, sodium and potassium absorption in the gastrointestinal tract by direct injection of the solutions in Tyrode to the rat colon in situ. The extent of the solubility of the compounds has also been assessed. The 1,8-dihydroxyanthracene structure seemed to be the best for hydragogue effect. Rhein-anthraquinone and -anthrone were the most active compounds tested.", "contents": "The influence of dihydroxyanthracene derivatives on water and electrolyte movement in rat colon. The purgative activities of 18 different dihydroxyanthracene derivatives, including free anthraquinones and anthrones, were investigated by determining their influence on the water, sodium and potassium absorption in the gastrointestinal tract by direct injection of the solutions in Tyrode to the rat colon in situ. The extent of the solubility of the compounds has also been assessed. The 1,8-dihydroxyanthracene structure seemed to be the best for hydragogue effect. Rhein-anthraquinone and -anthrone were the most active compounds tested."}
{"id": "PMID:7648", "title": "A dual action of 5-hydroxytryptamine on the ovarian suspensory ligament of the rat.", "content": "5-Hydroxytryptamine has a dual effect on the spontaneously contracting rat ovarian ligament, in vitro, a contraction which is antagonized by the prior administration of methysergide and a relaxation of the ligament observed in the methysergide-treated preparation. The relaxatory effect was not antagonized by propranolol or tetrodotoxin but treatment of the ligament with indomethacin abolished this response. Prostaglandins of the E series produced an inhibition, and PGF2alpha a contraction of the ligament. Thin layer chromatographic separation indicates that 5-HT causes the release of a PGE2-like substance which relaxes the ovarian suspensory ligament.", "contents": "A dual action of 5-hydroxytryptamine on the ovarian suspensory ligament of the rat. 5-Hydroxytryptamine has a dual effect on the spontaneously contracting rat ovarian ligament, in vitro, a contraction which is antagonized by the prior administration of methysergide and a relaxation of the ligament observed in the methysergide-treated preparation. The relaxatory effect was not antagonized by propranolol or tetrodotoxin but treatment of the ligament with indomethacin abolished this response. Prostaglandins of the E series produced an inhibition, and PGF2alpha a contraction of the ligament. Thin layer chromatographic separation indicates that 5-HT causes the release of a PGE2-like substance which relaxes the ovarian suspensory ligament."}
{"id": "PMID:7649", "title": "A model independent method for estimating the in vivo release rate constant of a drug from its oral formulations.", "content": "A simple equation by which the first-order release rate constant of a drug from its oral formulation can be calculated is derived. The derivation is independent of any hypothetical concepts of drug distribution or elimination.", "contents": "A model independent method for estimating the in vivo release rate constant of a drug from its oral formulations. A simple equation by which the first-order release rate constant of a drug from its oral formulation can be calculated is derived. The derivation is independent of any hypothetical concepts of drug distribution or elimination."}
{"id": "PMID:7650", "title": "The granulation of binary mixtures.", "content": "Granules have been prepared from blends of lactose and boric acid by the massing and screening method and their properties have been compared with those of granules from the individual materials, granulated separately. Increasing the volume of binder solution used produced granules stronger and of greater mean size in all blends studied. The largest and strongest granules, for any given binder solution volume and massing time, were obtained from a blend, as were the granules with the minimum pore size. The effect of massing time on granule properties was generally similar to those already reported for single component systems; prolonged massing in some blend led to a reduction in mean granule size. Variation in pre-mixing time produced no significant change in the physical properties of granules prepared from a lactose: boric acid blend.", "contents": "The granulation of binary mixtures. Granules have been prepared from blends of lactose and boric acid by the massing and screening method and their properties have been compared with those of granules from the individual materials, granulated separately. Increasing the volume of binder solution used produced granules stronger and of greater mean size in all blends studied. The largest and strongest granules, for any given binder solution volume and massing time, were obtained from a blend, as were the granules with the minimum pore size. The effect of massing time on granule properties was generally similar to those already reported for single component systems; prolonged massing in some blend led to a reduction in mean granule size. Variation in pre-mixing time produced no significant change in the physical properties of granules prepared from a lactose: boric acid blend."}
{"id": "PMID:7664", "title": "Stereoselective and calcium-dependent contractile effects of narcotic antagonist analgesics in the vascular smooth muscle of the rat.", "content": "In patients, pentazocine administered i.v. can have an unusual action for a strong analgesic-an elevation of blood pressure. The objective of this study in rats was to better quantify and explain the molecular mechanism for the vascular action of l-pentazocine and compare it with other analgesics and narcotic antagonists. In anesthetized rats, l-pentazocine (0.3-3 mg/kg i.v.) elevated blood pressure and this effect was potentiated in pithed rats. The contraction appeared to be nonadrenergic as it was not blocked by the alpha blocker, phenoxybenzamine. In vitro, morphine (ED50 = 4 X 10(-5) M) and the l-isomers of pentazocine (ED50 = 8 X 10(-6) M) contracted the spirally cut aortic strip. The l-isomers were approximately 5 times more potent than their d-enantiomers. Contraction of the aorta by l-pentazocine was not inhibited by dibenamine, atropine, diphenhydramine, pyrilamine or indomethacin nor potentiated by propranolol. On the other hand, not only was the contraction highly dependent on the concentration of calcium in the bath but it was also blocked by verapamil and SKF-525A, drugs known to inhibit transmembrane calcium influx. Naloxone (3 X 10(-4) to 1 X 10(-3) M), which produced no contractile effect by itself, reduced aortic contraction of l-pentazocine to the greatest extent, that of potassium moderately and that of norepinephrine only slightly. The naloxone blockade of l-pentazocine vascular contraction was reversed by increasing Ca++ concentration in the media, suggesting the action of naloxone may resemble a calcium blocker. It is proposed that a direct, stereoselective and calcium dependent vascular action of l-pentazocine contributes to its ability to raise blood pressure. The possibility that in high doses narcotic antagonists may decrease calcium influx should  also be considered.", "contents": "Stereoselective and calcium-dependent contractile effects of narcotic antagonist analgesics in the vascular smooth muscle of the rat. In patients, pentazocine administered i.v. can have an unusual action for a strong analgesic-an elevation of blood pressure. The objective of this study in rats was to better quantify and explain the molecular mechanism for the vascular action of l-pentazocine and compare it with other analgesics and narcotic antagonists. In anesthetized rats, l-pentazocine (0.3-3 mg/kg i.v.) elevated blood pressure and this effect was potentiated in pithed rats. The contraction appeared to be nonadrenergic as it was not blocked by the alpha blocker, phenoxybenzamine. In vitro, morphine (ED50 = 4 X 10(-5) M) and the l-isomers of pentazocine (ED50 = 8 X 10(-6) M) contracted the spirally cut aortic strip. The l-isomers were approximately 5 times more potent than their d-enantiomers. Contraction of the aorta by l-pentazocine was not inhibited by dibenamine, atropine, diphenhydramine, pyrilamine or indomethacin nor potentiated by propranolol. On the other hand, not only was the contraction highly dependent on the concentration of calcium in the bath but it was also blocked by verapamil and SKF-525A, drugs known to inhibit transmembrane calcium influx. Naloxone (3 X 10(-4) to 1 X 10(-3) M), which produced no contractile effect by itself, reduced aortic contraction of l-pentazocine to the greatest extent, that of potassium moderately and that of norepinephrine only slightly. The naloxone blockade of l-pentazocine vascular contraction was reversed by increasing Ca++ concentration in the media, suggesting the action of naloxone may resemble a calcium blocker. It is proposed that a direct, stereoselective and calcium dependent vascular action of l-pentazocine contributes to its ability to raise blood pressure. The possibility that in high doses narcotic antagonists may decrease calcium influx should  also be considered."}
{"id": "PMID:7665", "title": "Potassium release from the rat submaxillary gland in vitro. I. Induction by catecholamines.", "content": "Slices of submaxillary gland were incubated in vitro in an enriched Krebs-Ringer-bicarbonate medium gassed with 95% O2-5% CO2 at 37 degrees C and the release of K+ into the medium was monitored after stimulation with alpha and beta adrenergic secretagogues under a variety of experimental conditions. K+ was released by the slice system after addition of norepinephrine, epinephrine or phenylephrine, but not after addition of isoproterenol. The extent of K+ release after norepinephrine depends on the dose of secretagogue and is higher when glucose, adenine and inosine, or all three substrates are absent from the medium. The effect of norepinephrine on K+ release is reversed by phentolamine but not by propranolol. Phentolamine also causes a 9.4-fold shift to the right in the dose-response curve to norepinephrine. Addition of ouabain to the incubation medium results in a higher extent of K+ release and prevents the reversal caused by phentolamine. The response to norepinephrine fails to occur when Ca++ is absent from the medium, either by chelation with ethylene glycol bis (beta-amino-ethyl ether)-N,N'-tetraacetic acid or by elimination from the Krebs-Ringer solution, and shows gradations depending on the Ca++ content of the medium. By itself, however, Ca++ does not induce K+ release from the slice system. The following conclusions are derived from these observations: 1) the release of K+ ions from the submaxillary gland is mediated by alpha adrenergic receptors; 2) the net amount of K+ released is the result of two opposing and almost simultaneous mechanisms, a passive extrusion and an active reuptake; 3) the active reuptake of K+ depends on the availability of energy and is mediated through the ouabain-sensitive Na+-K+ activated adenosine triphosphatase; 4) the reaction is critically dependent on the presence of Ca++ in the incubation medium and probably involves an influx of Ca++ upon stimulation with alpha adrenergic secretagogues.", "contents": "Potassium release from the rat submaxillary gland in vitro. I. Induction by catecholamines. Slices of submaxillary gland were incubated in vitro in an enriched Krebs-Ringer-bicarbonate medium gassed with 95% O2-5% CO2 at 37 degrees C and the release of K+ into the medium was monitored after stimulation with alpha and beta adrenergic secretagogues under a variety of experimental conditions. K+ was released by the slice system after addition of norepinephrine, epinephrine or phenylephrine, but not after addition of isoproterenol. The extent of K+ release after norepinephrine depends on the dose of secretagogue and is higher when glucose, adenine and inosine, or all three substrates are absent from the medium. The effect of norepinephrine on K+ release is reversed by phentolamine but not by propranolol. Phentolamine also causes a 9.4-fold shift to the right in the dose-response curve to norepinephrine. Addition of ouabain to the incubation medium results in a higher extent of K+ release and prevents the reversal caused by phentolamine. The response to norepinephrine fails to occur when Ca++ is absent from the medium, either by chelation with ethylene glycol bis (beta-amino-ethyl ether)-N,N'-tetraacetic acid or by elimination from the Krebs-Ringer solution, and shows gradations depending on the Ca++ content of the medium. By itself, however, Ca++ does not induce K+ release from the slice system. The following conclusions are derived from these observations: 1) the release of K+ ions from the submaxillary gland is mediated by alpha adrenergic receptors; 2) the net amount of K+ released is the result of two opposing and almost simultaneous mechanisms, a passive extrusion and an active reuptake; 3) the active reuptake of K+ depends on the availability of energy and is mediated through the ouabain-sensitive Na+-K+ activated adenosine triphosphatase; 4) the reaction is critically dependent on the presence of Ca++ in the incubation medium and probably involves an influx of Ca++ upon stimulation with alpha adrenergic secretagogues."}
{"id": "PMID:7666", "title": "Comparison of uptake and binding of disodium cromoglycate and phenol red in rat lung.", "content": "In rat lung slices 3H-disodium cromoglycate (3H-DSCG) (0.001 mM) was taken up rapidly and 3H-DSCG tissue spaces, which equilibrated by 30 minutes, remained constant over a 4-hour incubation period. In contrast, 35S-phenol red (0.001 mM) accumulated in lung slices to a much greater extent than did DSCG, and the measured tissue spaces continued to increase over a 3-hour incubation period. In the presence of either phenol red (1 mM) or the metabolic inhibitors, iodoacetic acid (10(-4) M) and dinitrophenol (10(-4) M), 3H-DSCG uptake was significantly decreased. Accumulation of 3H-DSCG in lung slices and binding to tissue homogenates (pH 7.4) was also decreased when Ca and Mg ions were omitted from the bathing solution. Although DSCG and phenol red mutually inhibited the accumulation of one another over time in lung slices and 3H-DSCG (0.001 mM) binding to lung homogenates was decreased in the presence of 1 mM phenol red, 35S-phenol red efflux was not altered by the addition of 1 mM DSCG during the washout. Thus, it appears that, in rat lung, DSCG and phenol red share a common binding site(s) for uptake, possible on the transport \"carrier.\" Also, there appear to be additional pulmonary binding sites for phenol red. These sites are not occupied by DSCG and their presence could account for the differences observed in the extent of accumulation of the two compounds in lung slices.", "contents": "Comparison of uptake and binding of disodium cromoglycate and phenol red in rat lung. In rat lung slices 3H-disodium cromoglycate (3H-DSCG) (0.001 mM) was taken up rapidly and 3H-DSCG tissue spaces, which equilibrated by 30 minutes, remained constant over a 4-hour incubation period. In contrast, 35S-phenol red (0.001 mM) accumulated in lung slices to a much greater extent than did DSCG, and the measured tissue spaces continued to increase over a 3-hour incubation period. In the presence of either phenol red (1 mM) or the metabolic inhibitors, iodoacetic acid (10(-4) M) and dinitrophenol (10(-4) M), 3H-DSCG uptake was significantly decreased. Accumulation of 3H-DSCG in lung slices and binding to tissue homogenates (pH 7.4) was also decreased when Ca and Mg ions were omitted from the bathing solution. Although DSCG and phenol red mutually inhibited the accumulation of one another over time in lung slices and 3H-DSCG (0.001 mM) binding to lung homogenates was decreased in the presence of 1 mM phenol red, 35S-phenol red efflux was not altered by the addition of 1 mM DSCG during the washout. Thus, it appears that, in rat lung, DSCG and phenol red share a common binding site(s) for uptake, possible on the transport \"carrier.\" Also, there appear to be additional pulmonary binding sites for phenol red. These sites are not occupied by DSCG and their presence could account for the differences observed in the extent of accumulation of the two compounds in lung slices."}
{"id": "PMID:7667", "title": "Effect of sympathetic blocking agents on the antinatriuresis of reflex renal nerve stimulation.", "content": "To evaluate the effects of reflex renal sympathetic nerve stimulation on renal tubular sodium handling, clearance studies were performed in anesthetized dogs. With renal perfusion pressure held constant, baroreceptor reflex renal sympathetic nerve stimulation was produced by controlled arterial hemorrhage or carotid sinus perfusion. Significant decreases in urinary sodium excretion occurred in the presence of minor insignificant alterations in renal blood flow and no changes in glomerular filtration rate. Renal alpha adrenergic receptor blockade (phenoxybenzamine) or adrenergic blockade (guanethidine) completely reversed the fall in urinary sodium excretion; this could not be attributed to alterations in glomerular filtration rate or renal blood flow. These studies support the interpretation that adrenergic innervation of the renal tubules is involved in the regulation of renal tubular sodium reabsorption.", "contents": "Effect of sympathetic blocking agents on the antinatriuresis of reflex renal nerve stimulation. To evaluate the effects of reflex renal sympathetic nerve stimulation on renal tubular sodium handling, clearance studies were performed in anesthetized dogs. With renal perfusion pressure held constant, baroreceptor reflex renal sympathetic nerve stimulation was produced by controlled arterial hemorrhage or carotid sinus perfusion. Significant decreases in urinary sodium excretion occurred in the presence of minor insignificant alterations in renal blood flow and no changes in glomerular filtration rate. Renal alpha adrenergic receptor blockade (phenoxybenzamine) or adrenergic blockade (guanethidine) completely reversed the fall in urinary sodium excretion; this could not be attributed to alterations in glomerular filtration rate or renal blood flow. These studies support the interpretation that adrenergic innervation of the renal tubules is involved in the regulation of renal tubular sodium reabsorption."}
{"id": "PMID:7668", "title": "The pharmacology of flazalone: a new class of anti-inflammatory agent.", "content": "The anti-inflammatory activity of flazalone, a unique chemical drug, is described. In acute irritant anti-inflammatory tests, flazalone exhibited a wide spectrum of activity. The compound was active in affecting the course of paw swelling in adjuvant arthritis when given daily either at the outset of the polyarthritis or after induction. The most unusual aspect of this compound is its ability to inhibit graft rejection in goldfish and rabbits. The pattern of anti-inflammatory activity does not allow one to classify this drug in the usual groups.", "contents": "The pharmacology of flazalone: a new class of anti-inflammatory agent. The anti-inflammatory activity of flazalone, a unique chemical drug, is described. In acute irritant anti-inflammatory tests, flazalone exhibited a wide spectrum of activity. The compound was active in affecting the course of paw swelling in adjuvant arthritis when given daily either at the outset of the polyarthritis or after induction. The most unusual aspect of this compound is its ability to inhibit graft rejection in goldfish and rabbits. The pattern of anti-inflammatory activity does not allow one to classify this drug in the usual groups."}
{"id": "PMID:7669", "title": "Catecholamine-induced changes in ion transport in short-circuited frog skin and the effect of beta-blockade.", "content": "1. A method for measuring bidirectional Cl fluxes has been used to estimate net Cl movements in short-circuited frog skin and to compare these with the short-circuit current (Isc) and Na fluxes. 2. In some experiments bidirectional fluxes of both Na and Cl were measured simultaneously. It was found that the algebraic sum of the net fluxes of these two ions did not differ significantly from the values of Isc, either in untreated or catecholamine-treated skins, except for the half-hour period immediately after catecholamine addition. 3. The net effluxes of Cl produced by noradrenaline (1-6 X 10(-5)M), isoprenaline (8 X 10(-7)M) and adrenaline (6 and 15 X 10(-6)M) were of similar magnitude for each catecholamine. The magnitude of the Cl response measured as a flux ratio was related to a certain extent to the precatecholamine Cl conductance. 4. The net Na influx was increased by isoprenaline and reduced by noradrenaline. 5. Addition of the beta-adrenergic blocking agent oxprenolol (4-5 X 10(-5)M) to skins stimulated by catecholamine resulted in the disappearance of the net Cl movement and fall in skin conductance and Isc. This fall was similar in magnitude to, and correlated with the mean rise in Isc produced by isoprenaline, but of significantly greater magnitude in the case of noradrenaline. 6. The changes in Na influx were strongly associated with the changes in Isc following catecholamine addition. Similarly, the changes in Na efflux and Cl efflux were correlated, suggesting the Na fluxes to be dissociated, influx and efflux changes perhaps taking place at different loci. 7. Acetazolamide (1-2 X 10(-4)M), added either before or during the noradrenaline stimulation, had no effect on the Cl efflux response. 8. The tissue exchange of Cl from the outside bathing medium after 4 hr was greater in catecholamine-stimulated skins than in those in which the response had been blocked by oxprenolol. 9. These findings were taken to support a model entailing a neutral NaCl pump resident in the mucous glands and an epithelial Na pump enhanced by beta- and inhibited by alpha-adrenergic stimulation.", "contents": "Catecholamine-induced changes in ion transport in short-circuited frog skin and the effect of beta-blockade. 1. A method for measuring bidirectional Cl fluxes has been used to estimate net Cl movements in short-circuited frog skin and to compare these with the short-circuit current (Isc) and Na fluxes. 2. In some experiments bidirectional fluxes of both Na and Cl were measured simultaneously. It was found that the algebraic sum of the net fluxes of these two ions did not differ significantly from the values of Isc, either in untreated or catecholamine-treated skins, except for the half-hour period immediately after catecholamine addition. 3. The net effluxes of Cl produced by noradrenaline (1-6 X 10(-5)M), isoprenaline (8 X 10(-7)M) and adrenaline (6 and 15 X 10(-6)M) were of similar magnitude for each catecholamine. The magnitude of the Cl response measured as a flux ratio was related to a certain extent to the precatecholamine Cl conductance. 4. The net Na influx was increased by isoprenaline and reduced by noradrenaline. 5. Addition of the beta-adrenergic blocking agent oxprenolol (4-5 X 10(-5)M) to skins stimulated by catecholamine resulted in the disappearance of the net Cl movement and fall in skin conductance and Isc. This fall was similar in magnitude to, and correlated with the mean rise in Isc produced by isoprenaline, but of significantly greater magnitude in the case of noradrenaline. 6. The changes in Na influx were strongly associated with the changes in Isc following catecholamine addition. Similarly, the changes in Na efflux and Cl efflux were correlated, suggesting the Na fluxes to be dissociated, influx and efflux changes perhaps taking place at different loci. 7. Acetazolamide (1-2 X 10(-4)M), added either before or during the noradrenaline stimulation, had no effect on the Cl efflux response. 8. The tissue exchange of Cl from the outside bathing medium after 4 hr was greater in catecholamine-stimulated skins than in those in which the response had been blocked by oxprenolol. 9. These findings were taken to support a model entailing a neutral NaCl pump resident in the mucous glands and an epithelial Na pump enhanced by beta- and inhibited by alpha-adrenergic stimulation."}
{"id": "PMID:7670", "title": "The association between acidification and electrogenic events in the rat proximal jejunum.", "content": "1. Simultaneous measurement of hydrogen ion production, transmural potential difference and intermittent short-circuit current (SCC) was made in the rat proximal jejunum in vitro: similarly, potassium and sodium ion movements were measured to investigate the relationship of acidification to electrogenic events and associated ion movements in the jejunum.2. Acidification correlated significantly with the short-circuit current and both were inhibited by 10 mM serosal ouabain or 10 mM mucosal aminophylline. Both inhibitors had effects on net potassium movement but not on net sodium movement. Moreover, in isotope studies whereas 10 mM serosal ouabain reduced the J(ms) sodium flux, 10 mM mucosal aminophylline had no effect, i.e. aminophylline can reduce both short-circuit current and acidification without perceptibly altering the serosally directed sodium flux.3. In low-sodium buffers in which acidification still occurs although reduced, transmural potential differences occur of reversed polarity that are apparently unrelated to sodium diffusion potential differences (as evidenced by isotopic sodium efflux experiments) and which could be caused by hydrogen ion production. In low sodium buffers however the inhibitors have opposing effects, ouabain causing an increase and aminophylline a decrease in the reversed potential differences.4. A model for acidification (that of potassium rather than sodium ion exchange for the hydrogen ion and hydroxyl for chloride ion exchange) is proposed to explain the present experimental findings and other diverse observations in the literature: although either step might be the electrogenic step, acidification must be also considered as a component of the jejunal short-circuit current.", "contents": "The association between acidification and electrogenic events in the rat proximal jejunum. 1. Simultaneous measurement of hydrogen ion production, transmural potential difference and intermittent short-circuit current (SCC) was made in the rat proximal jejunum in vitro: similarly, potassium and sodium ion movements were measured to investigate the relationship of acidification to electrogenic events and associated ion movements in the jejunum.2. Acidification correlated significantly with the short-circuit current and both were inhibited by 10 mM serosal ouabain or 10 mM mucosal aminophylline. Both inhibitors had effects on net potassium movement but not on net sodium movement. Moreover, in isotope studies whereas 10 mM serosal ouabain reduced the J(ms) sodium flux, 10 mM mucosal aminophylline had no effect, i.e. aminophylline can reduce both short-circuit current and acidification without perceptibly altering the serosally directed sodium flux.3. In low-sodium buffers in which acidification still occurs although reduced, transmural potential differences occur of reversed polarity that are apparently unrelated to sodium diffusion potential differences (as evidenced by isotopic sodium efflux experiments) and which could be caused by hydrogen ion production. In low sodium buffers however the inhibitors have opposing effects, ouabain causing an increase and aminophylline a decrease in the reversed potential differences.4. A model for acidification (that of potassium rather than sodium ion exchange for the hydrogen ion and hydroxyl for chloride ion exchange) is proposed to explain the present experimental findings and other diverse observations in the literature: although either step might be the electrogenic step, acidification must be also considered as a component of the jejunal short-circuit current."}
{"id": "PMID:7671", "title": "In vitro treatment of human root surfaces with fluorides.", "content": "Two-minute topical applications with four different fluoride compounds, acidulated phosphate fluoride, sodium fluoride, sodium monofluorophosphate and stannous fluoride, were evaluated for ability to reduce the acide solubility of human root surfaces in vitro. Each fluoride was in aqueous solution with the fluoride level adjusted to 1.23 percent and the pH native. Rectangular windows were prepared on root surfaces and control versus test differences were invariably studied within teeth and not between teeth. Sodium fluoride and sodium monofluorophosphate solutions reduced root surface solubility by approximately 30 percent while acidulated phosphate fluoride and stannous fluoride were more than 2.5 times more effective, the solubility reduction exceeding 80 percent. Root surfaces thus are similar to enamel in their reactions to topically applied fluorides. Based upon these results the clinician should choose between acidulated phosphate fluoride and stannous fluoride when making the choice of a single treatment compound for office application.", "contents": "In vitro treatment of human root surfaces with fluorides. Two-minute topical applications with four different fluoride compounds, acidulated phosphate fluoride, sodium fluoride, sodium monofluorophosphate and stannous fluoride, were evaluated for ability to reduce the acide solubility of human root surfaces in vitro. Each fluoride was in aqueous solution with the fluoride level adjusted to 1.23 percent and the pH native. Rectangular windows were prepared on root surfaces and control versus test differences were invariably studied within teeth and not between teeth. Sodium fluoride and sodium monofluorophosphate solutions reduced root surface solubility by approximately 30 percent while acidulated phosphate fluoride and stannous fluoride were more than 2.5 times more effective, the solubility reduction exceeding 80 percent. Root surfaces thus are similar to enamel in their reactions to topically applied fluorides. Based upon these results the clinician should choose between acidulated phosphate fluoride and stannous fluoride when making the choice of a single treatment compound for office application."}
{"id": "PMID:7674", "title": "10-Hydroxy-4-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine derivatives (homobenzomorphans) as analgesics.", "content": "Six 10-hydroxy-4-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine derivatives 17a-f have been synthesized as potential analgesics. The synthesis of these compounds involved conversion of 4-(2-dimethylaminoethyl)-6-methoxy alpha tetralone derivatives 12a-f to their N-methyl analogues and the subsequent intramolecular mannich reaction with formaldehyde to give the 7-keto C-ring homobenzomorphans 14a-f from which 17a-f, respectively, were obtained. Compounds 17a-f are as potent as morphine as analgesics (mice).", "contents": "10-Hydroxy-4-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine derivatives (homobenzomorphans) as analgesics. Six 10-hydroxy-4-methyl-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine derivatives 17a-f have been synthesized as potential analgesics. The synthesis of these compounds involved conversion of 4-(2-dimethylaminoethyl)-6-methoxy alpha tetralone derivatives 12a-f to their N-methyl analogues and the subsequent intramolecular mannich reaction with formaldehyde to give the 7-keto C-ring homobenzomorphans 14a-f from which 17a-f, respectively, were obtained. Compounds 17a-f are as potent as morphine as analgesics (mice)."}
{"id": "PMID:7675", "title": "Potential histamine H2-receptor antagonists. 3. Methylhistamines.", "content": "Syntheses are described for all the mono- and some di- and trimethylhistamines. New methods are given for the known Npi, Ntau-, Nalpha-, 2-, and 4-methylhistamines and for the novel compounds, beta-methyl-, 4,Nalpha-dimethyl-, and 4,Nalpha,Nalpha-trimethylhistamines. Agonist activities are reported for stimulation of histamine H1 (guinea-pig ileum) and H2 (rat gastric acid secretion) receptors. H2-Receptor agonist activities indicate that a methyl group is more readily accommodated at the 4 and Nalpha positions than elsewhere in the histamine molecule and that receptor binding is substantially retained with a methyl substituent in these positions. Thus, for the design of potential antagonists, two sites are identified as being worthwhile exploring for the introduction of lipophilic substituents.", "contents": "Potential histamine H2-receptor antagonists. 3. Methylhistamines. Syntheses are described for all the mono- and some di- and trimethylhistamines. New methods are given for the known Npi, Ntau-, Nalpha-, 2-, and 4-methylhistamines and for the novel compounds, beta-methyl-, 4,Nalpha-dimethyl-, and 4,Nalpha,Nalpha-trimethylhistamines. Agonist activities are reported for stimulation of histamine H1 (guinea-pig ileum) and H2 (rat gastric acid secretion) receptors. H2-Receptor agonist activities indicate that a methyl group is more readily accommodated at the 4 and Nalpha positions than elsewhere in the histamine molecule and that receptor binding is substantially retained with a methyl substituent in these positions. Thus, for the design of potential antagonists, two sites are identified as being worthwhile exploring for the introduction of lipophilic substituents."}
{"id": "PMID:7676", "title": "Permeability parameters of the toad isolated stratum corneum.", "content": "A technique for isolating the stratum corneum from the subjacent layers of the epithelium was developed which permits studying the stratum corneum as an isolated membrane mounted between half-chambers. The method basically consists of an osmotic shock induced by immersing a piece of skin in distilled water at 50 degrees C for 2 min. When the membrane is bathed on each surface by NaCl-Ringer's solution, its electrical resistance is 14.1 +/- 1.3 omega cm2 (n=10). This value is about 1/100 of the whole skin resistance in the presence of the same solution. The hydraulic filtration coefficient (Lp) measured by a hydrostatic pressure method, with identical solutions on each side of the membrane, is 8.8 X 10(-5) +/- 1.5 X 10(-5) cm sec-1 atm-1 (n=10) in distilled water and 9.2 X 10(-5) +/- 1.4 X 10(-5) cm sec-1 atm-1 (n=10) in NaCl-Ringer's solution. These values are not statistically different and are within the range of 1/80 to 1/120 of the whole skin Lp. The stratum corneum shows an amphoteric character when studied by KCl diffusion potentials at different pH'S. The membrane presents an isoelectric pH of 4.6 +/- 0.3 (n=10). Above the isoelectric pH the potassium transport number is higher than the chloride transport number; below it, the reverse situation is valid. Divalent cations (Ca++ or Cu++) reduce membrane ionic discrimination when the membrane is negatively charged and are ineffective when the membrane fixed charges are protonated at low pH.", "contents": "Permeability parameters of the toad isolated stratum corneum. A technique for isolating the stratum corneum from the subjacent layers of the epithelium was developed which permits studying the stratum corneum as an isolated membrane mounted between half-chambers. The method basically consists of an osmotic shock induced by immersing a piece of skin in distilled water at 50 degrees C for 2 min. When the membrane is bathed on each surface by NaCl-Ringer's solution, its electrical resistance is 14.1 +/- 1.3 omega cm2 (n=10). This value is about 1/100 of the whole skin resistance in the presence of the same solution. The hydraulic filtration coefficient (Lp) measured by a hydrostatic pressure method, with identical solutions on each side of the membrane, is 8.8 X 10(-5) +/- 1.5 X 10(-5) cm sec-1 atm-1 (n=10) in distilled water and 9.2 X 10(-5) +/- 1.4 X 10(-5) cm sec-1 atm-1 (n=10) in NaCl-Ringer's solution. These values are not statistically different and are within the range of 1/80 to 1/120 of the whole skin Lp. The stratum corneum shows an amphoteric character when studied by KCl diffusion potentials at different pH'S. The membrane presents an isoelectric pH of 4.6 +/- 0.3 (n=10). Above the isoelectric pH the potassium transport number is higher than the chloride transport number; below it, the reverse situation is valid. Divalent cations (Ca++ or Cu++) reduce membrane ionic discrimination when the membrane is negatively charged and are ineffective when the membrane fixed charges are protonated at low pH."}
{"id": "PMID:7677", "title": "Anion transport and membrane morphology.", "content": "Freeze-fracture electronmicroscopy has been used to examine the membrane ultrastructure of human red blood cells in the presence of inhibitors of chloride exchange. The extent of inhibition was correlated with a decrease of intramembrane particle density on the B-fracture face. Dimethylsulfoxide (DMSO) and glycerol, which markedly and reversibly reduced the intramembrane particle density, were shown to drastically and reversibly inhibit chloride self-exchange. DMSO was shown to be a noncompetitive inhibitor of chloride flux.", "contents": "Anion transport and membrane morphology. Freeze-fracture electronmicroscopy has been used to examine the membrane ultrastructure of human red blood cells in the presence of inhibitors of chloride exchange. The extent of inhibition was correlated with a decrease of intramembrane particle density on the B-fracture face. Dimethylsulfoxide (DMSO) and glycerol, which markedly and reversibly reduced the intramembrane particle density, were shown to drastically and reversibly inhibit chloride self-exchange. DMSO was shown to be a noncompetitive inhibitor of chloride flux."}
{"id": "PMID:7681", "title": "Enzyme activities associated with an invertebrate iridovirus: nucleotide phosphohydrolase activity associated with iridescent virus type 6 (CIV).", "content": "A nucleoside triphosphate phosphohydrolase activity is firmly associated with a purified invertebrate iridovirus, iridescent virus type 6. The enzyme activity hydrolyzes all the nucleoside triphosphates, but has a high preference for ATP. The products of the reaction are nucleoside diphosphates. Conditions for nucleoside triphosphate phosphohydrolase activity are described.", "contents": "Enzyme activities associated with an invertebrate iridovirus: nucleotide phosphohydrolase activity associated with iridescent virus type 6 (CIV). A nucleoside triphosphate phosphohydrolase activity is firmly associated with a purified invertebrate iridovirus, iridescent virus type 6. The enzyme activity hydrolyzes all the nucleoside triphosphates, but has a high preference for ATP. The products of the reaction are nucleoside diphosphates. Conditions for nucleoside triphosphate phosphohydrolase activity are described."}
{"id": "PMID:7688", "title": "Hemodynamic effects of beta-adrenergic blockade with pindolol, oxprenolol, propranolol and bufetolol hydrochloride in essential hypertension.", "content": "Hemodynamic studies (using (131)I-labeled albumin [RISA]) Were performed before and 5 and 42 weeks after the oral administration of pindolol (av. 30 mg/day), oxprenolol (av. 216 mg/day), propranolol (av. 75 mg/day) or bufetolol hydrochloride (av. 30 mg/day) in 40 patients with essential hypertension. Responders to the antihypertensive actions of short-term (5 weeks) pindolol or bufetolol showed a reduction in total peripheral resistance (pindolol, from av. 2622 to 2022 dyne-sec-cm-5-m2; befetolol, from av. 3301 to 2620, p less than 0.05), without significant changes in cardiac index, while hypotensive actions of propranolol or oxprenolol appeared to be due mainly to a decrease in cardiac output (propranolol, from av. 4.03 to 2.99 L/min/m2; oxprenolol, from av. 3.97 to 3.29 L/min/m2), although the decrease in cardiac output was not significant. In long-term (42 weeks) oxprenolol therapy, antihypertensive effects seemed to be related to reduced cardiac output and a readaptation of peripheral resistance to chronic reduction of cardiac output was not always observed. Circulation time was determined in 9 patients with oxprenolol therapy and 8 with pindolol therapy by the measurement of the arrival time in the cerebral hemisphere of the intravenously injected radioisotope. The patients with oxprenolol therapy showed significant prolongation in circulation time (short-term administration, av. 6.6 to 8.4 sec; long-term administration av. 6.6 to 9.2 sec, p less than 0.05), while no prolongation was observed in pindolol therapy. These results suggest that hemodynamic responses to beta-blocking agents are not uniform and that the antihypertensive actions of beta-blockers depend on the effects on both cardiac output and peripheral vascular resistance.", "contents": "Hemodynamic effects of beta-adrenergic blockade with pindolol, oxprenolol, propranolol and bufetolol hydrochloride in essential hypertension. Hemodynamic studies (using (131)I-labeled albumin [RISA]) Were performed before and 5 and 42 weeks after the oral administration of pindolol (av. 30 mg/day), oxprenolol (av. 216 mg/day), propranolol (av. 75 mg/day) or bufetolol hydrochloride (av. 30 mg/day) in 40 patients with essential hypertension. Responders to the antihypertensive actions of short-term (5 weeks) pindolol or bufetolol showed a reduction in total peripheral resistance (pindolol, from av. 2622 to 2022 dyne-sec-cm-5-m2; befetolol, from av. 3301 to 2620, p less than 0.05), without significant changes in cardiac index, while hypotensive actions of propranolol or oxprenolol appeared to be due mainly to a decrease in cardiac output (propranolol, from av. 4.03 to 2.99 L/min/m2; oxprenolol, from av. 3.97 to 3.29 L/min/m2), although the decrease in cardiac output was not significant. In long-term (42 weeks) oxprenolol therapy, antihypertensive effects seemed to be related to reduced cardiac output and a readaptation of peripheral resistance to chronic reduction of cardiac output was not always observed. Circulation time was determined in 9 patients with oxprenolol therapy and 8 with pindolol therapy by the measurement of the arrival time in the cerebral hemisphere of the intravenously injected radioisotope. The patients with oxprenolol therapy showed significant prolongation in circulation time (short-term administration, av. 6.6 to 8.4 sec; long-term administration av. 6.6 to 9.2 sec, p less than 0.05), while no prolongation was observed in pindolol therapy. These results suggest that hemodynamic responses to beta-blocking agents are not uniform and that the antihypertensive actions of beta-blockers depend on the effects on both cardiac output and peripheral vascular resistance."}
{"id": "PMID:7693", "title": "Studies on the structure activity relationship of adrenergic beta-mimetic benzylamine derivatives.", "content": "Appropriately substituted benzylamine (BZA) derivatives, fragmented derivatives of tetrahydroisoquinolines, were found to be directly acting adrenergic beta-stimulants, exhibiting tracheal relaxing, positive chronotropic and free fatty acid (FFA) releasing activities. The chemical structures essential for manifestation of the beta-action were i) 3,4-dihydroxybenzylamine, ii) arylmethyl group at position alpha, iii) lower alkyl group on the N atom. The structure activity relationships of BZA-derivatives were almost similar to, but partly different from those of tetrahydroisoquinoline- and catecholamine-derivatives. The tracheal relaxing, positive chronotropic and FFA-releasing actions of alpha-(3,4,5-trimethoxybenzyl)-N-methyl-3,4-dihydroxybenzylamine, the most active compound in the BZA-derivatives tested, were approximately one-hundred, thirty and fifty times less active than those of ISO, respectively. These results indicate that this compound is beta1-selective, while trimetoquinol is beta2-selective.", "contents": "Studies on the structure activity relationship of adrenergic beta-mimetic benzylamine derivatives. Appropriately substituted benzylamine (BZA) derivatives, fragmented derivatives of tetrahydroisoquinolines, were found to be directly acting adrenergic beta-stimulants, exhibiting tracheal relaxing, positive chronotropic and free fatty acid (FFA) releasing activities. The chemical structures essential for manifestation of the beta-action were i) 3,4-dihydroxybenzylamine, ii) arylmethyl group at position alpha, iii) lower alkyl group on the N atom. The structure activity relationships of BZA-derivatives were almost similar to, but partly different from those of tetrahydroisoquinoline- and catecholamine-derivatives. The tracheal relaxing, positive chronotropic and FFA-releasing actions of alpha-(3,4,5-trimethoxybenzyl)-N-methyl-3,4-dihydroxybenzylamine, the most active compound in the BZA-derivatives tested, were approximately one-hundred, thirty and fifty times less active than those of ISO, respectively. These results indicate that this compound is beta1-selective, while trimetoquinol is beta2-selective."}
{"id": "PMID:7694", "title": "alpha-Adrenoceptors mediating positive inotropic effects on the ventricular myocardium: some aspects of structure-activity relationship of sympathomimetic amines.", "content": "Experiments were carried out on the isolated papillary muscle of the rabbit in order to further characterize the alpha-adrenoceptors mediating the positive inotropic effect. For this purpose dose-response relations of seven sympathomimetic amines were compared under the influence of alpha- and/or beta-adrenolytic drugs. Phentolamine (10(-6) M) shifted the lower part of the dose-response curves for norfenephrine, synephrine and epinine as for phenylephrine and adrenaline to the right, while prindolol (10(-8) M) affected only the upper part of the curves. In the presence of both alpha- and beta-adrenoceptor blocking agents the entire dose-response curves for sympathomimetic amines were shifted in a parallel manner. Noradrenaline affected preferentially beta-adrenoceptors, whereas its effect on alpha-adrenoceptors was so weak that it could be detected only when the neuronal and extraneuronal uptake mechanism of amines were blocked by cocaine (3 X 10(-5) M) and corticosterone (4 X 10(-5) M), respectively. The effect of dopamine was not affected either by phentolamine or by prindolol, but was antagonized by the simultaneous application of both alpha- and beta-adrenoceptor blocking agents. From the present results, it appears that the following relationships are present between the structure of amines and the alpha-adrenoceptor stimulating activity in the heart: (1) N-methylation increases the potency: (2) Absence of the hydroxyl group either in 3 or in 4 position decreases the intrinsic and beta-adrenoceptor stimulating activities, but increases the alpha-adrenoceptor stimulating activity.", "contents": "alpha-Adrenoceptors mediating positive inotropic effects on the ventricular myocardium: some aspects of structure-activity relationship of sympathomimetic amines. Experiments were carried out on the isolated papillary muscle of the rabbit in order to further characterize the alpha-adrenoceptors mediating the positive inotropic effect. For this purpose dose-response relations of seven sympathomimetic amines were compared under the influence of alpha- and/or beta-adrenolytic drugs. Phentolamine (10(-6) M) shifted the lower part of the dose-response curves for norfenephrine, synephrine and epinine as for phenylephrine and adrenaline to the right, while prindolol (10(-8) M) affected only the upper part of the curves. In the presence of both alpha- and beta-adrenoceptor blocking agents the entire dose-response curves for sympathomimetic amines were shifted in a parallel manner. Noradrenaline affected preferentially beta-adrenoceptors, whereas its effect on alpha-adrenoceptors was so weak that it could be detected only when the neuronal and extraneuronal uptake mechanism of amines were blocked by cocaine (3 X 10(-5) M) and corticosterone (4 X 10(-5) M), respectively. The effect of dopamine was not affected either by phentolamine or by prindolol, but was antagonized by the simultaneous application of both alpha- and beta-adrenoceptor blocking agents. From the present results, it appears that the following relationships are present between the structure of amines and the alpha-adrenoceptor stimulating activity in the heart: (1) N-methylation increases the potency: (2) Absence of the hydroxyl group either in 3 or in 4 position decreases the intrinsic and beta-adrenoceptor stimulating activities, but increases the alpha-adrenoceptor stimulating activity."}
{"id": "PMID:7695", "title": "Desensitization of guinea pig tracheal muscle preparation to beta-adrenergic stimulants by a preceding exposure to a high dose of catecholamines.", "content": "When a given concentration of a catecholamine was applied to guinea pig tracheal preparation contracted by 20 muM histamine or by 30 mM-K+-Tyrode's solution, constant relaxations were observed, if the relaxation was submaximal. When a high concentration of catecholamine, 200 times the ED50, was once applied, subsequent responses to beta-stimulants (ED80) was reduced by about 30-40%, in spite of repeated washings. The response was gradually recovered in 2 hr. Thus 45 muM epinephrine and 1 muM isoproterenol could cause desensitization to 0.65 muM EPINEPHRINE AND 0.03 muM isoproterenol, respectively. Epinephrine and isoproterenol could cause densensitization to isoprophenamine, a non-catechol beta-stimulant. Epinephrine did not affect the response to cyclic AMP, dibutyryl cyclic AMP, aminophylline and prostaglandin E1. This densensitization was not affected by phentolamine, normetanephrine nor by Ca2+ deprivation from the bathing solution. The mechanisms of the desensitization may relate to some step(s) between the receptor-drug interaction and cyclic AMP accumulation in the process of tracheal muscle relaxation induced by beta-stimulants.", "contents": "Desensitization of guinea pig tracheal muscle preparation to beta-adrenergic stimulants by a preceding exposure to a high dose of catecholamines. When a given concentration of a catecholamine was applied to guinea pig tracheal preparation contracted by 20 muM histamine or by 30 mM-K+-Tyrode's solution, constant relaxations were observed, if the relaxation was submaximal. When a high concentration of catecholamine, 200 times the ED50, was once applied, subsequent responses to beta-stimulants (ED80) was reduced by about 30-40%, in spite of repeated washings. The response was gradually recovered in 2 hr. Thus 45 muM epinephrine and 1 muM isoproterenol could cause desensitization to 0.65 muM EPINEPHRINE AND 0.03 muM isoproterenol, respectively. Epinephrine and isoproterenol could cause densensitization to isoprophenamine, a non-catechol beta-stimulant. Epinephrine did not affect the response to cyclic AMP, dibutyryl cyclic AMP, aminophylline and prostaglandin E1. This densensitization was not affected by phentolamine, normetanephrine nor by Ca2+ deprivation from the bathing solution. The mechanisms of the desensitization may relate to some step(s) between the receptor-drug interaction and cyclic AMP accumulation in the process of tracheal muscle relaxation induced by beta-stimulants."}
{"id": "PMID:7697", "title": "Approach to acid-base problems in the critically ill and injured.", "content": "The use of the Henderson-Hasselbalch equation and the relationships between bicarbonate levels and the pCO2 or carbonic acid concentration in evaluating acid-base abnormalities are explained. The etiology, pathophysiology, diagnosis and treatment of respiratory alkalosis and acidosis and metabolic alkalosis and acidosis are discussed. The results of laboratory tests should be examined in relation to the patient's condition and consistency with other laboratory tests. Therapy is directed at correcting the underlying problems and, secondarily, at correcting the numbers. Patients respond primarily to rate of change and not absolute numbers. Therefore, problems should be corrected at approximately the rate they develop. Treatment should be guided by continued patient observation and serial laboratory studies.", "contents": "Approach to acid-base problems in the critically ill and injured. The use of the Henderson-Hasselbalch equation and the relationships between bicarbonate levels and the pCO2 or carbonic acid concentration in evaluating acid-base abnormalities are explained. The etiology, pathophysiology, diagnosis and treatment of respiratory alkalosis and acidosis and metabolic alkalosis and acidosis are discussed. The results of laboratory tests should be examined in relation to the patient's condition and consistency with other laboratory tests. Therapy is directed at correcting the underlying problems and, secondarily, at correcting the numbers. Patients respond primarily to rate of change and not absolute numbers. Therefore, problems should be corrected at approximately the rate they develop. Treatment should be guided by continued patient observation and serial laboratory studies."}
{"id": "PMID:7699", "title": "[Dynamic observations of tolerance to physical exercise in patients with ischemic heart disease during drug therapy].", "content": "Proceeding from a dynamic observation of the tolerance of physical exercises in the process of drug therapy of 90 patients with ischaemic heart disease the author concludes that a certain dissociation exists between the subjective effect of the antianginal drugs and the results of bicycle tests in the evaluation of the efficacy of the treatment. While a subjective improvement was declared in 2/3 of the patients, the exercise test indices improved only in 1/3. The bicylce test before and after the therapeutic course seems to facilitate a more precise evaluation of the efficacy of the antianginal drugs.", "contents": "[Dynamic observations of tolerance to physical exercise in patients with ischemic heart disease during drug therapy]. Proceeding from a dynamic observation of the tolerance of physical exercises in the process of drug therapy of 90 patients with ischaemic heart disease the author concludes that a certain dissociation exists between the subjective effect of the antianginal drugs and the results of bicycle tests in the evaluation of the efficacy of the treatment. While a subjective improvement was declared in 2/3 of the patients, the exercise test indices improved only in 1/3. The bicylce test before and after the therapeutic course seems to facilitate a more precise evaluation of the efficacy of the antianginal drugs."}
{"id": "PMID:7700", "title": "[Arterial hypertension and chronic hemodialysis].", "content": "Basing on the literature data and their own observations of patients with chronic hemodialysis the authors have analysed the pathogenesis, course, hemodynamic shifts and possibilities of purposeful treatment in terminal uremia. Besides two variants of the hypertension course (controlled and noncontrolled), a third type has been revealed--hypertension difficult to control, in the pathogenesis of which, as well as in the noncontrolled variant, an important role is played by the activization of the renin-angiotensin system. Hemodynamic mechanizms of an abrupt change in the arterial pressure (acute hypotension and hypertensive crisis) in the process of hemodialysis are analysed.", "contents": "[Arterial hypertension and chronic hemodialysis]. Basing on the literature data and their own observations of patients with chronic hemodialysis the authors have analysed the pathogenesis, course, hemodynamic shifts and possibilities of purposeful treatment in terminal uremia. Besides two variants of the hypertension course (controlled and noncontrolled), a third type has been revealed--hypertension difficult to control, in the pathogenesis of which, as well as in the noncontrolled variant, an important role is played by the activization of the renin-angiotensin system. Hemodynamic mechanizms of an abrupt change in the arterial pressure (acute hypotension and hypertensive crisis) in the process of hemodialysis are analysed."}
{"id": "PMID:7701", "title": "[Use of beta-blockader visken in children with primary arterial hypertension].", "content": "The effect of Visken was analysed in children with primary arterial hypertension, Stage IB, with reference to their general state, dynamics of cardiac contractions, arterial pressure, cardiac output, and vascular peripheral resistance. The treatment was undertaken in 28 children lasting from 6 to 8 weeks. A multiformity of the drug's effect upon the state of the children with early hypertension was noted. The response of different parameters of the circulatory system to Visken is individual. Side effects may develop against the background of even low doses.", "contents": "[Use of beta-blockader visken in children with primary arterial hypertension]. The effect of Visken was analysed in children with primary arterial hypertension, Stage IB, with reference to their general state, dynamics of cardiac contractions, arterial pressure, cardiac output, and vascular peripheral resistance. The treatment was undertaken in 28 children lasting from 6 to 8 weeks. A multiformity of the drug's effect upon the state of the children with early hypertension was noted. The response of different parameters of the circulatory system to Visken is individual. Side effects may develop against the background of even low doses."}
{"id": "PMID:7705", "title": "Vasopressin-stimulated movement of drugs and uric acid across the toad urinary bladder.", "content": "Vasopressin is known to increase the permeability of the toad bladder, an analogue of the mammalian collecting duct, to water and hydrophilic solutes such as urea. In the present study, the effect of vasopressin on the permeability of a series of lipophilic compounds, including many commonly used drugs, has been determined. In all cases, permeability increased from 50 to 100%. The response to vasopressin was mediated by cyclic adenosine monophosphate (cAMP), and was generally not altered by phloretin, an agent that inhibits amide movement through the amide transport pathway. Evidence that these compounds move directly through the lipid phase of the membrane was provided in studies of phenobarbital permeability at low and high luminal pH. We would conclude from these studies that the effect of vasopressin on the luminal cell membrane is a widespread one, modifying both lipid components and components involved in amide, sodium and water transport. This may be of importance in the renal tubular reabsorption of many drugs, including barbiturates, glutethimide and antibiotics.", "contents": "Vasopressin-stimulated movement of drugs and uric acid across the toad urinary bladder. Vasopressin is known to increase the permeability of the toad bladder, an analogue of the mammalian collecting duct, to water and hydrophilic solutes such as urea. In the present study, the effect of vasopressin on the permeability of a series of lipophilic compounds, including many commonly used drugs, has been determined. In all cases, permeability increased from 50 to 100%. The response to vasopressin was mediated by cyclic adenosine monophosphate (cAMP), and was generally not altered by phloretin, an agent that inhibits amide movement through the amide transport pathway. Evidence that these compounds move directly through the lipid phase of the membrane was provided in studies of phenobarbital permeability at low and high luminal pH. We would conclude from these studies that the effect of vasopressin on the luminal cell membrane is a widespread one, modifying both lipid components and components involved in amide, sodium and water transport. This may be of importance in the renal tubular reabsorption of many drugs, including barbiturates, glutethimide and antibiotics."}
{"id": "PMID:7707", "title": "Isohydric regulation of plasma potassium by bicarbonate in the rat.", "content": "pH and bicarbonate affect many metabolic reactions but each may change independently. To study bicarbonate's effect onplasma potassium, blood bicarbonate in normal, hypokalemic or hyperkalemic rats was either maintained constant, lowered by hydrochloric acid or raised by sodium bicarbonate administraion. Blood pH was maintained constant by changing PCO2. In normokalemia lowering bicarbonate increased plasma potassium 2.0mEq above values obtained in the other groups. To eliminate urinary potassium losses, experiments were also performed in rats with bilateral ureteral ligation. Again, plasma potassium concentration rose significantly more in the lowered bicarbonate group. Similarly, in hypokalemia, plasma potassium rose 1.2 and 0.4mEq in the lowered and unchanged groups, but fell 0.2mEq/liter in the elevated group. Differences could not be ascribed to renal potassium losses as potassium excretion was essentially zero in each group. In hyperkalemia, plasma potassium concentration remained elevated for 150 min in the lowered bicarbonate group but fell 1.3 and 2.0mEq in the unchanged and elevated groups, respectively. Urinary potassium losses in the three groups were statistically identical. In all experiments blood pH was maintained unchanged during the experiment. The data show that bicarbonate,  independent of blood pH, alters transcellular potassium distribution suggesting the usefulness of bicarbonate therapy in hyperkalemia even at a compensated blood pH.", "contents": "Isohydric regulation of plasma potassium by bicarbonate in the rat. pH and bicarbonate affect many metabolic reactions but each may change independently. To study bicarbonate's effect onplasma potassium, blood bicarbonate in normal, hypokalemic or hyperkalemic rats was either maintained constant, lowered by hydrochloric acid or raised by sodium bicarbonate administraion. Blood pH was maintained constant by changing PCO2. In normokalemia lowering bicarbonate increased plasma potassium 2.0mEq above values obtained in the other groups. To eliminate urinary potassium losses, experiments were also performed in rats with bilateral ureteral ligation. Again, plasma potassium concentration rose significantly more in the lowered bicarbonate group. Similarly, in hypokalemia, plasma potassium rose 1.2 and 0.4mEq in the lowered and unchanged groups, but fell 0.2mEq/liter in the elevated group. Differences could not be ascribed to renal potassium losses as potassium excretion was essentially zero in each group. In hyperkalemia, plasma potassium concentration remained elevated for 150 min in the lowered bicarbonate group but fell 1.3 and 2.0mEq in the unchanged and elevated groups, respectively. Urinary potassium losses in the three groups were statistically identical. In all experiments blood pH was maintained unchanged during the experiment. The data show that bicarbonate,  independent of blood pH, alters transcellular potassium distribution suggesting the usefulness of bicarbonate therapy in hyperkalemia even at a compensated blood pH."}
{"id": "PMID:7708", "title": "Lithium-induced impairment of urine acidification.", "content": "The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium  administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron.", "contents": "Lithium-induced impairment of urine acidification. The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium  administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron."}
{"id": "PMID:7714", "title": "Immunoregulation and autoimmunity.", "content": "The immunologic responses, both cell-mediated and humoral, to exogenous antigens reflect a crucial balance between extrinsic forces which can either augment or suppress the reactivity of T and B effector cells. It is probable that similar immunoregulatory influences play a key role in maintaining tolerance to some self-antigens. Thus, despite the presence of cells potentially capable of reacting to autologous antigens, lack of autoimmunity might reflect either an absence of amplifying or a preponderance of suppressive immunoregulatory forces. Within this framework, data obtained indicating aberrances of immunoregulation in patients with systemic lupus erythematosus are discussed, specifically as the aberrances may be causally related to the autoimmune nature of this disease.", "contents": "Immunoregulation and autoimmunity. The immunologic responses, both cell-mediated and humoral, to exogenous antigens reflect a crucial balance between extrinsic forces which can either augment or suppress the reactivity of T and B effector cells. It is probable that similar immunoregulatory influences play a key role in maintaining tolerance to some self-antigens. Thus, despite the presence of cells potentially capable of reacting to autologous antigens, lack of autoimmunity might reflect either an absence of amplifying or a preponderance of suppressive immunoregulatory forces. Within this framework, data obtained indicating aberrances of immunoregulation in patients with systemic lupus erythematosus are discussed, specifically as the aberrances may be causally related to the autoimmune nature of this disease."}
{"id": "PMID:7712", "title": "Properties of monomeric paramyosin using a transient electric birefringence techniques.", "content": "Paramyosin samples obtained from the chowder clam, Mercenaria mercenaria, by different extraction techniques were studied using transient electric birefringence techniques. The protein remain monomeric (unaggregated) in 1 mM buffer solution at pH 3.1 to 3.8 and near pH 10. At pH 3.2, the molecules obtained by different extraction techniques exhibit rotational diffusion constants that indicate a 5% difference in length between them, with the probable native form of paramyosin being the longer species. This difference in rotational diffusion constant disappears at higher pH, and, in addition, a large difference in dipole moment between the molecules observed at pH 3.2 also disappears at high pH. These results are used to hypothesize that the rodlike native paramyosin molecules have one or two partly flexible portions on their ends; at one end of each molecule this portion probably contains excess basic amino acids which are charged at low pH to account for the higher dipole moment of this form of paramyosin at these low pH values. At pH 3.2, these portions of the macromolecule are not flexible and act as stiff parts of the rodlike molecules, but they gradually become flexible at higher pH. Possible mechanisms for this change in flexibility are discussed.", "contents": "Properties of monomeric paramyosin using a transient electric birefringence techniques. Paramyosin samples obtained from the chowder clam, Mercenaria mercenaria, by different extraction techniques were studied using transient electric birefringence techniques. The protein remain monomeric (unaggregated) in 1 mM buffer solution at pH 3.1 to 3.8 and near pH 10. At pH 3.2, the molecules obtained by different extraction techniques exhibit rotational diffusion constants that indicate a 5% difference in length between them, with the probable native form of paramyosin being the longer species. This difference in rotational diffusion constant disappears at higher pH, and, in addition, a large difference in dipole moment between the molecules observed at pH 3.2 also disappears at high pH. These results are used to hypothesize that the rodlike native paramyosin molecules have one or two partly flexible portions on their ends; at one end of each molecule this portion probably contains excess basic amino acids which are charged at low pH to account for the higher dipole moment of this form of paramyosin at these low pH values. At pH 3.2, these portions of the macromolecule are not flexible and act as stiff parts of the rodlike molecules, but they gradually become flexible at higher pH. Possible mechanisms for this change in flexibility are discussed."}
{"id": "PMID:7715", "title": "Ageing of Neurospora crassa. IV. Induction of senescence in wild type by dietary amino acid analogs and reversal by antioxidants and membrane stabilizers.", "content": "The extensional growth rate of wild-type 74A8 N. crassa in the presence of various concentrations of 19 amino acid analogs was measured. Seven analogs were not inhibitory at concentrations in the range of one to 10mM. Of the remaining 12 analogs, nine inhibited growth in a novel way. The kinetics of growth in the presence of these analogs at 30 degrees were characterized by seven sequential phases: (1)lag; (2) acceleration of growth rate; (3) steady-state growth rate; (4) exponential rate of decline of growth rate; (5) no growth or growth rate less than or equal to 0.1 mm h-1; (6) accleration of growth rate; and (7) steady state. At 33 degrees, phases 6 and 7 did not occur and irreparable death of the clones occurred. The mechanism by which the clones acquired resistance at 30 degrees appeared to involve a combination of physiological adaptation and cellular selection. Dietary application of either free radical scavengers or surface-active membrane 'stabilizers' alleviated or prevented the inhibition and deterioration of growth rate which occurred in the presence of the nine amino acid analogs. Culture with either 4-fluorophenylalanine or ethionine led to an increase of the activities of antioxygenic enzymes glutathione peroxidase, glutathione reductase and superoxide dismutase. The amino acid analogs that cause senescence and death of growing cells are known to be incorporated into proteins and such proteins are generally abnormal. Because a substantial fraction of cellular protein occurs in membranes and the proteins synthesized by mitochondria are exclusively intrinsic membrane proteins, we suggest that  a primary consequence of errors in protein synthesis is the production of faulty membranes. The deterioration of such membranes with associated lipid autoxidation and free radical production proceeding as a chain reaction at an exponential rate may in itself contribute to the exponential rate of cellular deterioration which is characteristic of the ageing process. According to this hypothesis, dietary membrane stabilizers, free radical scavengers and antioxygenic enzymes protect cells from error catastrophy arising from the chain of events leading from membrane deterioration.", "contents": "Ageing of Neurospora crassa. IV. Induction of senescence in wild type by dietary amino acid analogs and reversal by antioxidants and membrane stabilizers. The extensional growth rate of wild-type 74A8 N. crassa in the presence of various concentrations of 19 amino acid analogs was measured. Seven analogs were not inhibitory at concentrations in the range of one to 10mM. Of the remaining 12 analogs, nine inhibited growth in a novel way. The kinetics of growth in the presence of these analogs at 30 degrees were characterized by seven sequential phases: (1)lag; (2) acceleration of growth rate; (3) steady-state growth rate; (4) exponential rate of decline of growth rate; (5) no growth or growth rate less than or equal to 0.1 mm h-1; (6) accleration of growth rate; and (7) steady state. At 33 degrees, phases 6 and 7 did not occur and irreparable death of the clones occurred. The mechanism by which the clones acquired resistance at 30 degrees appeared to involve a combination of physiological adaptation and cellular selection. Dietary application of either free radical scavengers or surface-active membrane 'stabilizers' alleviated or prevented the inhibition and deterioration of growth rate which occurred in the presence of the nine amino acid analogs. Culture with either 4-fluorophenylalanine or ethionine led to an increase of the activities of antioxygenic enzymes glutathione peroxidase, glutathione reductase and superoxide dismutase. The amino acid analogs that cause senescence and death of growing cells are known to be incorporated into proteins and such proteins are generally abnormal. Because a substantial fraction of cellular protein occurs in membranes and the proteins synthesized by mitochondria are exclusively intrinsic membrane proteins, we suggest that  a primary consequence of errors in protein synthesis is the production of faulty membranes. The deterioration of such membranes with associated lipid autoxidation and free radical production proceeding as a chain reaction at an exponential rate may in itself contribute to the exponential rate of cellular deterioration which is characteristic of the ageing process. According to this hypothesis, dietary membrane stabilizers, free radical scavengers and antioxygenic enzymes protect cells from error catastrophy arising from the chain of events leading from membrane deterioration."}
{"id": "PMID:7727", "title": "[Binding of silver ions by Candida utilis cells].", "content": "Binding of silver ions by the cells of Candida utilis involves their adsorption on the cell surface. It was found that 90% of all silver bound by the cells was localized in the fraction of cell walls and cytoplasmic membranes. The sensitivity of protoplasts to the toxic action of silver ions is much higher than that of intact cells. The toxic effect of silver ions is supposed to be related to changes in the functions of cytoplasmic membranes.", "contents": "[Binding of silver ions by Candida utilis cells]. Binding of silver ions by the cells of Candida utilis involves their adsorption on the cell surface. It was found that 90% of all silver bound by the cells was localized in the fraction of cell walls and cytoplasmic membranes. The sensitivity of protoplasts to the toxic action of silver ions is much higher than that of intact cells. The toxic effect of silver ions is supposed to be related to changes in the functions of cytoplasmic membranes."}
{"id": "PMID:7731", "title": "The possible role of beta-adrenergic and alpha-adrenergic antagonist sensitive systems in the brain in the mechanism of psychosis.", "content": "On the basis of clinical observations on psychotic patients during treatment with adrenergic blocking drugs it is postulated that normally the activities of two systems in the brain are balanced: one of these systems can be blocked by beta-adrenergic blocking drugs and the other is responsive to alpha-adrenergic blocking drugs. Psychosis may occur when either the total activity is too high or too low, or when the balance is disturbed. Specific psychiatric syndromes are outlined as related to either of these systems.", "contents": "The possible role of beta-adrenergic and alpha-adrenergic antagonist sensitive systems in the brain in the mechanism of psychosis. On the basis of clinical observations on psychotic patients during treatment with adrenergic blocking drugs it is postulated that normally the activities of two systems in the brain are balanced: one of these systems can be blocked by beta-adrenergic blocking drugs and the other is responsive to alpha-adrenergic blocking drugs. Psychosis may occur when either the total activity is too high or too low, or when the balance is disturbed. Specific psychiatric syndromes are outlined as related to either of these systems."}
{"id": "PMID:7743", "title": "[The mechanism of action of d-amino acid oxidase. I. Evidence for a free radical mechanism of the reaction catalyzed b a dimeric form of the enzyme].", "content": "d-Amino acid oxidase can oxidize the substrate to a ketoacid in the absence of oxygen. The stoichiometry of this reaction is precisely 1 molecule of keto acid for 1 molecule of enzyme, containing two flavin groups. Hence, the flavin must be in the semi-reduced free radical state. But these free radicals cannot be visualized by ESR spectroscopy because of closeness and strong interaction. After the acid denaturation of the protein the coenzyme is released as a semi-reduced free radical. An alternative method of registration is the transfer of the free radical state to an added excess of free flavin molecules. By both methods it is quantitatively determined that each flavin of the enzyme is reduced to a free radical. Therefore, we believe to have evidenced unambiguously that this enzymatic reaction proceeds via a free radical transition state.", "contents": "[The mechanism of action of d-amino acid oxidase. I. Evidence for a free radical mechanism of the reaction catalyzed b a dimeric form of the enzyme]. d-Amino acid oxidase can oxidize the substrate to a ketoacid in the absence of oxygen. The stoichiometry of this reaction is precisely 1 molecule of keto acid for 1 molecule of enzyme, containing two flavin groups. Hence, the flavin must be in the semi-reduced free radical state. But these free radicals cannot be visualized by ESR spectroscopy because of closeness and strong interaction. After the acid denaturation of the protein the coenzyme is released as a semi-reduced free radical. An alternative method of registration is the transfer of the free radical state to an added excess of free flavin molecules. By both methods it is quantitatively determined that each flavin of the enzyme is reduced to a free radical. Therefore, we believe to have evidenced unambiguously that this enzymatic reaction proceeds via a free radical transition state."}
{"id": "PMID:7744", "title": "[The fluorescence of pepsin conjugates with DNS-chloride].", "content": "Parameters of rotational relaxation of pepsin conjugated in neutral and slightly alkaline solutions with a fluorescent label 1-dimethylaminonaphthalene-5-sulphonyl chloride (DNS-Cl) are measured by a fluorescence polarization method. It is shown that the globule of pepsin denatured and loose at lakaline pH values converts into a compact form after transfer to acidic solution. The compactness of this new form is close to that of native inhibited pepsin. A new globule is distinguished from the native by the absence of segmental flexibility. Conjugated with a DNS at pH less than or equal to 7.0 pepsin relaxes in solution as catalytically active dansylated aminopepsin (DNS-3-aminotyrosine pepsin). Evidence is presented that these conjugates are also characterized by segmental flexibility.", "contents": "[The fluorescence of pepsin conjugates with DNS-chloride]. Parameters of rotational relaxation of pepsin conjugated in neutral and slightly alkaline solutions with a fluorescent label 1-dimethylaminonaphthalene-5-sulphonyl chloride (DNS-Cl) are measured by a fluorescence polarization method. It is shown that the globule of pepsin denatured and loose at lakaline pH values converts into a compact form after transfer to acidic solution. The compactness of this new form is close to that of native inhibited pepsin. A new globule is distinguished from the native by the absence of segmental flexibility. Conjugated with a DNS at pH less than or equal to 7.0 pepsin relaxes in solution as catalytically active dansylated aminopepsin (DNS-3-aminotyrosine pepsin). Evidence is presented that these conjugates are also characterized by segmental flexibility."}
{"id": "PMID:7749", "title": "Rat and mouse tissue-mediated mutagenicity of ring-substituted 3,3-dimethyl-1-phenyltriazenes in Salmonella typhimurium.", "content": "3,3-Dimethyl-1-phenyltriazene and a series of ring-substituted derivatives (X-phi-N=N-N-(CH3)2:X=substituent(s); phi=phenyl) were tested for their mutagenic and toxic action upon Salmonella typhimurium G-46 in a liquid incubation system containing 9000 g tissue supernatants and an NADPH-generating system. The compounds could be grouped into four classes according to their toxicity and mutagenicity after 1 h incubation at 37 degrees C at a concentration of 5 mM in the presence of liver supernatant fractions from phenobarbitone-pretreated mice. When a liver supernatant from untreated mice was compared with one from phenobarbitone-pretreated animals, the mutagenic effect of a series of triazenes (with X=H; 4-chloro; 4-chloro; 4-bromo; 2,4,6-trichloro) in vitro was enhanced twice to ten times. The toxicity of triazenes with X=4-methoxy or 4-acetamido was strongly decreased by a liver fraction from phenobarbitone-pretreated mice in the presence of an NADPH-generating system. With 3,3-dimethyl-1-phenyl-triazene, rat liver fractions caused a lower enzyme-mediated mutagenicity in S. typhimurium G-46 than those of mouse liver, whereas a 9000 g supernatant from brain, a major target organ for the carcinogenic action of certain triazenes, was unable, in either species, to generate metabolites mutagenic for S. typhimurium G-46.", "contents": "Rat and mouse tissue-mediated mutagenicity of ring-substituted 3,3-dimethyl-1-phenyltriazenes in Salmonella typhimurium. 3,3-Dimethyl-1-phenyltriazene and a series of ring-substituted derivatives (X-phi-N=N-N-(CH3)2:X=substituent(s); phi=phenyl) were tested for their mutagenic and toxic action upon Salmonella typhimurium G-46 in a liquid incubation system containing 9000 g tissue supernatants and an NADPH-generating system. The compounds could be grouped into four classes according to their toxicity and mutagenicity after 1 h incubation at 37 degrees C at a concentration of 5 mM in the presence of liver supernatant fractions from phenobarbitone-pretreated mice. When a liver supernatant from untreated mice was compared with one from phenobarbitone-pretreated animals, the mutagenic effect of a series of triazenes (with X=H; 4-chloro; 4-chloro; 4-bromo; 2,4,6-trichloro) in vitro was enhanced twice to ten times. The toxicity of triazenes with X=4-methoxy or 4-acetamido was strongly decreased by a liver fraction from phenobarbitone-pretreated mice in the presence of an NADPH-generating system. With 3,3-dimethyl-1-phenyl-triazene, rat liver fractions caused a lower enzyme-mediated mutagenicity in S. typhimurium G-46 than those of mouse liver, whereas a 9000 g supernatant from brain, a major target organ for the carcinogenic action of certain triazenes, was unable, in either species, to generate metabolites mutagenic for S. typhimurium G-46."}
{"id": "PMID:7745", "title": "[Fibrinogen and fibrin monomer conformation changes dependent of pH magnitude].", "content": "Conformational states of fibrinogen and fibrin monomer were studied by methods of differential and solvent-perturbation spectrophotometry and ultraviolet fluorescence at about neutral pH (6.5) and in the region of lower pH, 3.2 to 4.0. To prevent repolymerization of fibrin monomer at pH 6.5, urea was added in a non-denaturing concentration of 1.7 M. In the acid region specified, the immediate environment of tyrosine and tryptophan residues was found to be more polar and the accessibility to perturbants higher than at pH 6.5. Much more drastic changes of the same type occurred at pH less than 3 when denaturation of the protein takes place. The conformation of fibrinogen altered progressively upon lowering pH from 4.0 to 3.2. This acidity increase, practically, did not influence the conformation of fibrin monomer. Thus the tolerance of the latter to the appearance of the new positively changed groups seems to be comparably high. The bulk of the conformational changes subsequent upon neutralization of an acid fibrin monomer solution proceeds at a higher rate than the activation transition, i.e. the acquirement of a state of polymerization readiness by fibrin monomer molecules.", "contents": "[Fibrinogen and fibrin monomer conformation changes dependent of pH magnitude]. Conformational states of fibrinogen and fibrin monomer were studied by methods of differential and solvent-perturbation spectrophotometry and ultraviolet fluorescence at about neutral pH (6.5) and in the region of lower pH, 3.2 to 4.0. To prevent repolymerization of fibrin monomer at pH 6.5, urea was added in a non-denaturing concentration of 1.7 M. In the acid region specified, the immediate environment of tyrosine and tryptophan residues was found to be more polar and the accessibility to perturbants higher than at pH 6.5. Much more drastic changes of the same type occurred at pH less than 3 when denaturation of the protein takes place. The conformation of fibrinogen altered progressively upon lowering pH from 4.0 to 3.2. This acidity increase, practically, did not influence the conformation of fibrin monomer. Thus the tolerance of the latter to the appearance of the new positively changed groups seems to be comparably high. The bulk of the conformational changes subsequent upon neutralization of an acid fibrin monomer solution proceeds at a higher rate than the activation transition, i.e. the acquirement of a state of polymerization readiness by fibrin monomer molecules."}
{"id": "PMID:7750", "title": "Chemical composition and some properties of modified buffalo milk for infant feeding.", "content": "A proposed formula for modifying buffalo milk for infant feeding was described. Buffalo milk was diluted with four parts of whey that was produced by addition of citric acid or lemon juice to milk and neutralization with sodium bicarbonate. The chemical composition and the properties of the proposed formula were compared with raw buffalo milk, human milk and buffalo milk modified by the ordinary method. The proposed formula was characterised by low casein/whey protein N comparable to human milk and by curd tension.", "contents": "Chemical composition and some properties of modified buffalo milk for infant feeding. A proposed formula for modifying buffalo milk for infant feeding was described. Buffalo milk was diluted with four parts of whey that was produced by addition of citric acid or lemon juice to milk and neutralization with sodium bicarbonate. The chemical composition and the properties of the proposed formula were compared with raw buffalo milk, human milk and buffalo milk modified by the ordinary method. The proposed formula was characterised by low casein/whey protein N comparable to human milk and by curd tension."}
{"id": "PMID:7751", "title": "[Retention of apple starch in production of pectin by the aluminum pectinate procedure].", "content": "Apple pectin produced by means of the aluminum pectinate procedure contains less starch than apple pectin obtained by precipitation with ethanol. The degradatin of the starch which occurs during production depends to a great extent upon the conditions of pomace digestion. The absorption maxima of the amylose-iodine complexes range in general from 550 to 570 nm. Model experiments with highly esterified pectin and partially degraded (by mechanolysis) apple starches were performed to establish favourable conditions for fractionating the pectin and starch components which are obtained when the pectin is precipitated as aluminum pectinate and when the granular coagulate is washed with water.", "contents": "[Retention of apple starch in production of pectin by the aluminum pectinate procedure]. Apple pectin produced by means of the aluminum pectinate procedure contains less starch than apple pectin obtained by precipitation with ethanol. The degradatin of the starch which occurs during production depends to a great extent upon the conditions of pomace digestion. The absorption maxima of the amylose-iodine complexes range in general from 550 to 570 nm. Model experiments with highly esterified pectin and partially degraded (by mechanolysis) apple starches were performed to establish favourable conditions for fractionating the pectin and starch components which are obtained when the pectin is precipitated as aluminum pectinate and when the granular coagulate is washed with water."}
{"id": "PMID:7746", "title": "[The circular dichroism spectrum of dinucleoside phosphate analogs].", "content": "Circular dichroism spectra of 11 analogues of the dinucleoside phosphate containing achiral 3'-terminal monomers have been measured at several pH values, various temperatures and various concentrations of ethanol. The conformation of analogues studied has been shown to by very similar to that of natural compounds. Comparison of the results obtained with the circular dichroism spectra of the corresponding natural compounds indicates that Cotton effect arises from monomeric circular dichroism, at least in main features. The exciton interaction is relatively small.", "contents": "[The circular dichroism spectrum of dinucleoside phosphate analogs]. Circular dichroism spectra of 11 analogues of the dinucleoside phosphate containing achiral 3'-terminal monomers have been measured at several pH values, various temperatures and various concentrations of ethanol. The conformation of analogues studied has been shown to by very similar to that of natural compounds. Comparison of the results obtained with the circular dichroism spectra of the corresponding natural compounds indicates that Cotton effect arises from monomeric circular dichroism, at least in main features. The exciton interaction is relatively small."}
{"id": "PMID:7752", "title": "Mechanisms of tyrosine hydroxylase and dopamine beta-hydroxylase induction in organ cultures of rat sympathetic ganglia by potassium depolarization and cholinomimetics.", "content": "It was the aim of the present study to elucidate the mechanisms involved in specific tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) induction by potassium depolarization and cholinomimetics in rat superior cervical ganglia kept in organ culture. The effect of high (54 mM) potassium concentration on intact ganglia seems to result in a dual action: a) a specific induction of TH and DBH via release of acetylcholine from preganglionic cholinergic nerve terminals. b) a non-specific effect on terminal adrenergic neurons resulting in a general increase of protein synthesis as indicated by the increase in DOPA decarboxylase (DDC) and monoamine oxidase (MAO) activities. In decentralized superior cervical ganglia potassium depolarization failed to produce the specific TH and DBH induction although a small increase in DDC activity persisted. Carbamylcholine, acetylcholine and nicotine at concentrations of 10(-4) M elicited a selective induction of TH and DBH both in intact and decentralized ganglia via nicotinic receptor stimulation. Bethanechol, predominantly stimulating muscarinic receptors had no significant effect on TH activity. A 4 h pulse of 10(-4) M carbamylcholine produced optimal induction of DBH and TH 24 h and 48 h later respectively. Longer exposure to carbamylcholine resulted in a significantly smaller rise in TH activity.", "contents": "Mechanisms of tyrosine hydroxylase and dopamine beta-hydroxylase induction in organ cultures of rat sympathetic ganglia by potassium depolarization and cholinomimetics. It was the aim of the present study to elucidate the mechanisms involved in specific tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) induction by potassium depolarization and cholinomimetics in rat superior cervical ganglia kept in organ culture. The effect of high (54 mM) potassium concentration on intact ganglia seems to result in a dual action: a) a specific induction of TH and DBH via release of acetylcholine from preganglionic cholinergic nerve terminals. b) a non-specific effect on terminal adrenergic neurons resulting in a general increase of protein synthesis as indicated by the increase in DOPA decarboxylase (DDC) and monoamine oxidase (MAO) activities. In decentralized superior cervical ganglia potassium depolarization failed to produce the specific TH and DBH induction although a small increase in DDC activity persisted. Carbamylcholine, acetylcholine and nicotine at concentrations of 10(-4) M elicited a selective induction of TH and DBH both in intact and decentralized ganglia via nicotinic receptor stimulation. Bethanechol, predominantly stimulating muscarinic receptors had no significant effect on TH activity. A 4 h pulse of 10(-4) M carbamylcholine produced optimal induction of DBH and TH 24 h and 48 h later respectively. Longer exposure to carbamylcholine resulted in a significantly smaller rise in TH activity."}
{"id": "PMID:7753", "title": "Anti-dopaminergic and anti-muscarinic effects of dibenzodiazepines: relationship to drug induced Parkinsonism.", "content": "1. The anti-dopaminergic effects of several dibenzodiazepines were examined on the dopamine-stimulated adenylate cyclase in rat striatal homogenates. The \"cis\" isomer of clozapine, HF-2046, was the most potent in this respect and perlapine, which is devoid of neuroleptic activity, was the weakest. 2. The anti-muscarinic effects of the same compounds were measured by using the muscarinic affinity label 3H-propylbenzilylcholine mustard. HF-2046 was the most potent and loxapine the least potent of the drugs used. 3. The anti-dopaminergic effects of the drugs correlate well with neuroleptic but not with extrapyramidal effects. The anti-dopaminergic/anti-muscarinic ratio, however, correlates well with extrapyramidal rather than neuroleptic effects.", "contents": "Anti-dopaminergic and anti-muscarinic effects of dibenzodiazepines: relationship to drug induced Parkinsonism. 1. The anti-dopaminergic effects of several dibenzodiazepines were examined on the dopamine-stimulated adenylate cyclase in rat striatal homogenates. The \"cis\" isomer of clozapine, HF-2046, was the most potent in this respect and perlapine, which is devoid of neuroleptic activity, was the weakest. 2. The anti-muscarinic effects of the same compounds were measured by using the muscarinic affinity label 3H-propylbenzilylcholine mustard. HF-2046 was the most potent and loxapine the least potent of the drugs used. 3. The anti-dopaminergic effects of the drugs correlate well with neuroleptic but not with extrapyramidal effects. The anti-dopaminergic/anti-muscarinic ratio, however, correlates well with extrapyramidal rather than neuroleptic effects."}
{"id": "PMID:7747", "title": "[A study of the physico-chemical properties of lecithin membranes using hydrophobic and hydrophilic spin probes].", "content": "Some physico-chemical properties of lecithin lyposomes and the effects of pH, temperature and ionic strength changes are studied by ESR using hydrophobic and hydrophylic nitroxyl radicals as spin probes. The structure differences between outer and inner layers of bilayer liposomes are observed using auxiliary water soluble paramagnetic complex and attributed tentatively to the different curvature signs of both layers. Lower estimates of transversal diffusion rates of both probes throught the membrane are obtained using exchange broadening technique and water soluble reducing agent. The limiting step in this diffusion is revealed, caused by the transport of a charged group of the diffusing molecule through the hydrophobic membrane space.", "contents": "[A study of the physico-chemical properties of lecithin membranes using hydrophobic and hydrophilic spin probes]. Some physico-chemical properties of lecithin lyposomes and the effects of pH, temperature and ionic strength changes are studied by ESR using hydrophobic and hydrophylic nitroxyl radicals as spin probes. The structure differences between outer and inner layers of bilayer liposomes are observed using auxiliary water soluble paramagnetic complex and attributed tentatively to the different curvature signs of both layers. Lower estimates of transversal diffusion rates of both probes throught the membrane are obtained using exchange broadening technique and water soluble reducing agent. The limiting step in this diffusion is revealed, caused by the transport of a charged group of the diffusing molecule through the hydrophobic membrane space."}
{"id": "PMID:7754", "title": "Lack of correlation between changes in cyclic nucleotides and subsequent induction of tyrosine hydroxylase in rat adrenal medulla.", "content": "Pretreatment of rats with dexamethasone (2.5 mumol/kg, a dose which blocks the release of ACTH from the pituitary gland) abolished the reserpine mediated increase in cAMP and the increase in the cAMP/cGMP ratio in the adrenal medulla. In contrast, the reserpine-mediated induction of tyrosine hydroxylase (TH) remained unchanged. Hypophysectomy had a similar effect to dexamethasone treatment. Since changes in cAMP and changes in the cAMP/cGMP ratio are not indispensible prerequisities for the subsequent induction of TH, a causal relationship between the two phenomena seems to be excluded.", "contents": "Lack of correlation between changes in cyclic nucleotides and subsequent induction of tyrosine hydroxylase in rat adrenal medulla. Pretreatment of rats with dexamethasone (2.5 mumol/kg, a dose which blocks the release of ACTH from the pituitary gland) abolished the reserpine mediated increase in cAMP and the increase in the cAMP/cGMP ratio in the adrenal medulla. In contrast, the reserpine-mediated induction of tyrosine hydroxylase (TH) remained unchanged. Hypophysectomy had a similar effect to dexamethasone treatment. Since changes in cAMP and changes in the cAMP/cGMP ratio are not indispensible prerequisities for the subsequent induction of TH, a causal relationship between the two phenomena seems to be excluded."}
{"id": "PMID:7748", "title": "[Kinetic patterns of bacterial hydrogenase inactivation].", "content": "Kinetics of inactivation of hydrogenases is exemplified with the enzyme from Chloropseudomonas ethylica. The effect of gaseous phase, temperature, pH on the inactivation kinetics has been studied. Inactivation of the hydrogenase during incubation of an enzyme solution in air has been studied. Analysis of the kinetic data allowed the conclusion to be made that inactivation involves two forms of the enzyme which differ in their activity and resistance to inactivating actions. Stabilities of the mean time of operation of hydrogenases from Chloropseudomonas ethylica and Thiocapsa roseopersicina are compared. The mechanism of inactivation of hydrogenases from the two sources were found to be similar in many ways.", "contents": "[Kinetic patterns of bacterial hydrogenase inactivation]. Kinetics of inactivation of hydrogenases is exemplified with the enzyme from Chloropseudomonas ethylica. The effect of gaseous phase, temperature, pH on the inactivation kinetics has been studied. Inactivation of the hydrogenase during incubation of an enzyme solution in air has been studied. Analysis of the kinetic data allowed the conclusion to be made that inactivation involves two forms of the enzyme which differ in their activity and resistance to inactivating actions. Stabilities of the mean time of operation of hydrogenases from Chloropseudomonas ethylica and Thiocapsa roseopersicina are compared. The mechanism of inactivation of hydrogenases from the two sources were found to be similar in many ways."}
{"id": "PMID:7761", "title": "Prolonged infusion of diazoxide in the management of premature labor in the baboon.", "content": "The management of premature labor by the prolonged infusion of diazoxide was evaluated in 33 pregnant baboons. The drug was administered intravenously to the mother with an average rate of 0.065 mg/kg/min for 4 hours. Mild to moderate spontaneous labors were significantly inhibited by diazoxide without jeopardizing the fetus. Diazoxide produced a significant increase in maternal heart rate, but its effect on fetal circulation was minimal. Fetal acid-base state and arterial oxygenation remained essentially unchanged throughout the period of observation. Intravenous administration of this drug to the fetuses caused only mild cardiovascular changes irrespective of its preexisting conditions. Thus, a slow intravenous infusion of diazoxide to the mother in a low dosage appears to be of value for inhibiting the uterine activity in early labor, without interfering with the fetal well-being.", "contents": "Prolonged infusion of diazoxide in the management of premature labor in the baboon. The management of premature labor by the prolonged infusion of diazoxide was evaluated in 33 pregnant baboons. The drug was administered intravenously to the mother with an average rate of 0.065 mg/kg/min for 4 hours. Mild to moderate spontaneous labors were significantly inhibited by diazoxide without jeopardizing the fetus. Diazoxide produced a significant increase in maternal heart rate, but its effect on fetal circulation was minimal. Fetal acid-base state and arterial oxygenation remained essentially unchanged throughout the period of observation. Intravenous administration of this drug to the fetuses caused only mild cardiovascular changes irrespective of its preexisting conditions. Thus, a slow intravenous infusion of diazoxide to the mother in a low dosage appears to be of value for inhibiting the uterine activity in early labor, without interfering with the fetal well-being."}
{"id": "PMID:7762", "title": "[Effect of actinomycin D on transformation of the planulae of Obelia loveni (Allman)].", "content": "The incubation of planulae Obelia loveni in the actinomycin D solution (40 mug/ml) for 3 hrs at 17--20 degrees resulted in the marked inhibition of the process of attachment of planulae to the substrate and their transformation in polyps. A suggestion is put forward that at the final phase of larval development a special RNA is synthesized which participates in the genetically determined control of the complicated morphogenetic phenomenon of attachment and transformation of the planula in polyp.", "contents": "[Effect of actinomycin D on transformation of the planulae of Obelia loveni (Allman)]. The incubation of planulae Obelia loveni in the actinomycin D solution (40 mug/ml) for 3 hrs at 17--20 degrees resulted in the marked inhibition of the process of attachment of planulae to the substrate and their transformation in polyps. A suggestion is put forward that at the final phase of larval development a special RNA is synthesized which participates in the genetically determined control of the complicated morphogenetic phenomenon of attachment and transformation of the planula in polyp."}
{"id": "PMID:7765", "title": "Leukocyte function and characterization of leukocyte glucose-6-phosphate dehydrogenase in Sicilian mutants.", "content": "Nine Sicilian children known to be deficient in glucose-6-phosphate dehyrdrogenase (G6PD) were studied to see if there were anomalies of bactericidal activity in peripheral blood phagocytes. The type of deficiency was established. The G6PD levels in the leukocyte were found to be 26% of the controls (0.094 +/- 0.03, normal controls 0.360 +/- 0.12). The Michaelis constant for NADP and glucose-6-phosphate (G6P) was lower than the control. Conversely, the utilization of the analogous 2-deoxyglucose-6-phosphate (2dG6P) and galactose-6-phosphate (Ga16P) was higher. The thermostability of the enzyme in the deficient subjects was lower and the pH optima (8 and 9.5) were different from the controls. An identical electrophoretic pattern was found in both normal and deficient subjects. The bactericidal activity in the deficient subjects was normal. There was no difference in the results of nitroblue tetrazolium (NBT) tests in either group.", "contents": "Leukocyte function and characterization of leukocyte glucose-6-phosphate dehydrogenase in Sicilian mutants. Nine Sicilian children known to be deficient in glucose-6-phosphate dehyrdrogenase (G6PD) were studied to see if there were anomalies of bactericidal activity in peripheral blood phagocytes. The type of deficiency was established. The G6PD levels in the leukocyte were found to be 26% of the controls (0.094 +/- 0.03, normal controls 0.360 +/- 0.12). The Michaelis constant for NADP and glucose-6-phosphate (G6P) was lower than the control. Conversely, the utilization of the analogous 2-deoxyglucose-6-phosphate (2dG6P) and galactose-6-phosphate (Ga16P) was higher. The thermostability of the enzyme in the deficient subjects was lower and the pH optima (8 and 9.5) were different from the controls. An identical electrophoretic pattern was found in both normal and deficient subjects. The bactericidal activity in the deficient subjects was normal. There was no difference in the results of nitroblue tetrazolium (NBT) tests in either group."}
{"id": "PMID:7766", "title": "Child's urinary lithiasis revealing a complete deficit in adenine phosphoribosyl transferase.", "content": "In one case of a urinary lithiasis, termed \"uric lithiasis\" on biochemical examination, the authors describe the symptomatology of a child with a complete deficit in adenine phosphoribosyl transferase. After more intensive investigation the calculi have been found to be composed of a new clinical compound: 2,8-hydroxyadenine.", "contents": "Child's urinary lithiasis revealing a complete deficit in adenine phosphoribosyl transferase. In one case of a urinary lithiasis, termed \"uric lithiasis\" on biochemical examination, the authors describe the symptomatology of a child with a complete deficit in adenine phosphoribosyl transferase. After more intensive investigation the calculi have been found to be composed of a new clinical compound: 2,8-hydroxyadenine."}
{"id": "PMID:7767", "title": "Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth.", "content": "The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2).", "contents": "Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth. The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2)."}
{"id": "PMID:7768", "title": "Pneumothorax in the respiratory distress syndrome: incidence and effect on vital signs, blood gases, and pH.", "content": "We determined the incidence of pneumothorax in 295 infants (mean birthweight, 1,917 gm) with the respiratory distress syndrome (RDS) treated according to the same protocol. Fifty-five infants (mean birthweight, 1,594 gm) developed pneumothorax (incidence, 19%); incidence varied with severity of RDS and intensity of respiratory assistance. Pneumothorax occurred in 3.5% (2 of 58) of infants who received no assisted ventilation and in 11% (14 of 124) of infants who received continuous positive airway pressure (CPAP) as the only form of assisted ventilation; the difference between these two groups is not significant. Forty-nine infants initially treated with CPAP later required mechanical ventilation with positive end-expiratory pressure (PEEP). Pneumothorax occurred in 12 of the 49 (24%) and in 21 of 64 (33%) of those infants initially treated with PEEP; the incidence of pneumothorax for both these groups was significantly higher than for those treated with no assisted ventilation or CPAP only. To assess the value of frequent measurement of vital signs, blood gas tensions, and pH in the recognition of pneumothorax, we analyzed these variables by the cumulative sum statistical technique. We noted the following significant changes associated with pneumothorax: arterial blood pressure, heart rate, and respiratory rate decreased in 77% of cases; pulse pressure narrowed in 51% of cases; Po2 decreased in 17 of 20 cases in which ventilatory settings were constant for at least three hours prior to pneumothorax. However, pH and Pco2 showed consistent changes. Frequent measurements of vital signs and Po2 aid in the early diagnosis of pneumothorax.", "contents": "Pneumothorax in the respiratory distress syndrome: incidence and effect on vital signs, blood gases, and pH. We determined the incidence of pneumothorax in 295 infants (mean birthweight, 1,917 gm) with the respiratory distress syndrome (RDS) treated according to the same protocol. Fifty-five infants (mean birthweight, 1,594 gm) developed pneumothorax (incidence, 19%); incidence varied with severity of RDS and intensity of respiratory assistance. Pneumothorax occurred in 3.5% (2 of 58) of infants who received no assisted ventilation and in 11% (14 of 124) of infants who received continuous positive airway pressure (CPAP) as the only form of assisted ventilation; the difference between these two groups is not significant. Forty-nine infants initially treated with CPAP later required mechanical ventilation with positive end-expiratory pressure (PEEP). Pneumothorax occurred in 12 of the 49 (24%) and in 21 of 64 (33%) of those infants initially treated with PEEP; the incidence of pneumothorax for both these groups was significantly higher than for those treated with no assisted ventilation or CPAP only. To assess the value of frequent measurement of vital signs, blood gas tensions, and pH in the recognition of pneumothorax, we analyzed these variables by the cumulative sum statistical technique. We noted the following significant changes associated with pneumothorax: arterial blood pressure, heart rate, and respiratory rate decreased in 77% of cases; pulse pressure narrowed in 51% of cases; Po2 decreased in 17 of 20 cases in which ventilatory settings were constant for at least three hours prior to pneumothorax. However, pH and Pco2 showed consistent changes. Frequent measurements of vital signs and Po2 aid in the early diagnosis of pneumothorax."}
{"id": "PMID:7769", "title": "Acid-base measurements of arterial, venous and capillary blood in the dog.", "content": "A method of arterial blood sampling acceptable for clinical purposes for acid-base estimations in dogs is described. A comparison of acid-base variables from fourteen canine arterial, venous and capillary blood samples revealed in most cases that venous and capillary blood samples showed unsatisfactory agreement with corresponding arterial blood samples. Two commercial automatic pH and blood-gas analysing systems are compared.", "contents": "Acid-base measurements of arterial, venous and capillary blood in the dog. A method of arterial blood sampling acceptable for clinical purposes for acid-base estimations in dogs is described. A comparison of acid-base variables from fourteen canine arterial, venous and capillary blood samples revealed in most cases that venous and capillary blood samples showed unsatisfactory agreement with corresponding arterial blood samples. Two commercial automatic pH and blood-gas analysing systems are compared."}
{"id": "PMID:7770", "title": "The occurrence of Bacillus cereus in Finnish dog food sausages; a microbiological and physiochemical survey.", "content": "A bacteriological survey of five brands of commercial dog food sausages showed that two of them were heavily contaminated with B. cereus. One of the two brands had a suspected association with food-poisoning incidents in dogs. In addition to B. cereus the other sausage brand was found to contain a high number of sulphite reducing anaerobes. B. cereus was detected in almost every raw material of the two brands of sausages. The pasteurization during manufacturing did not kill all the sporeforming organisms. The water activity of the sausages were equal to or more than 0.99 and pH in a range from 6.2 to 7.0. Methods of preventing the growth of microbes in the sausages after manufacturing are discussed.", "contents": "The occurrence of Bacillus cereus in Finnish dog food sausages; a microbiological and physiochemical survey. A bacteriological survey of five brands of commercial dog food sausages showed that two of them were heavily contaminated with B. cereus. One of the two brands had a suspected association with food-poisoning incidents in dogs. In addition to B. cereus the other sausage brand was found to contain a high number of sulphite reducing anaerobes. B. cereus was detected in almost every raw material of the two brands of sausages. The pasteurization during manufacturing did not kill all the sporeforming organisms. The water activity of the sausages were equal to or more than 0.99 and pH in a range from 6.2 to 7.0. Methods of preventing the growth of microbes in the sausages after manufacturing are discussed."}
{"id": "PMID:7772", "title": "New fluorescent cytidine 5'-phosphate derivatives.", "content": "Interaction of cytidine 5'-phosphate with chloroacetone or p-tosyloxyacetone leads to 2-methyl-5,6-dihydro-5-oxo-6-(5-0-phospho-beta-D-ribofuranosyl)-imidazo/1,2-c/pyrimidine (2-methylethenocytidine 5'-phosphate) whereas analogous reaction with phenacyl bromide produces similar 2-phenyl-derivative. The bicyclic nucleotides obtained showed significant UV absorption at long wavelength where common nucleotides and proteins exhibited no absorption. These derivatives are highly fluorescent when heterocyclic ring is protonated. The absorption and fluorescent properties of the substituted ethenocytidine 5'-phosphoate derivatives seem to be suitable for their use as fluorescent probes or labels in biochemical studies.", "contents": "New fluorescent cytidine 5'-phosphate derivatives. Interaction of cytidine 5'-phosphate with chloroacetone or p-tosyloxyacetone leads to 2-methyl-5,6-dihydro-5-oxo-6-(5-0-phospho-beta-D-ribofuranosyl)-imidazo/1,2-c/pyrimidine (2-methylethenocytidine 5'-phosphate) whereas analogous reaction with phenacyl bromide produces similar 2-phenyl-derivative. The bicyclic nucleotides obtained showed significant UV absorption at long wavelength where common nucleotides and proteins exhibited no absorption. These derivatives are highly fluorescent when heterocyclic ring is protonated. The absorption and fluorescent properties of the substituted ethenocytidine 5'-phosphoate derivatives seem to be suitable for their use as fluorescent probes or labels in biochemical studies."}
{"id": "PMID:7775", "title": "The effects of antipyretics on metabolism processes in rat liver mitochondria. Part I. The action of sodium salicylate, and pyrazolones on the reaction of respiratory chain.", "content": "The effects of sodium salicylate (SS), phenazone (Ph) and aminophenazone (APh) on mitochondrial respiration respiration and oxidative phosphorylation were studied in vitro, SS inhibited state 3 but stimulated state 4 of respiration, if alpha-ketoglutarate and succinate were used as the substrates. The inhibition of state 3 of respiration was not reversed by 2,4-dinitrophenol (DNP). Ph and APh inhibited the respiratory state 3 without affecting the state 4 in the presence of the same substrates, and the produced inhibition in state 3 was reversible by DNP. Studies on ATP synthesis have revealed that SS was the only antypyretic tested that exerted an uncoupling action. SS stimulated the mitochondrial ATPase activity but inhibited it after uncoupling of oxidative phosphorylation with DNP. The mitochondrial ATPase activity remained uninfluenced by Ph or APh. The only similar action of all the drugs investigated was the inhibition of oxidation in the respiratory state 3.", "contents": "The effects of antipyretics on metabolism processes in rat liver mitochondria. Part I. The action of sodium salicylate, and pyrazolones on the reaction of respiratory chain. The effects of sodium salicylate (SS), phenazone (Ph) and aminophenazone (APh) on mitochondrial respiration respiration and oxidative phosphorylation were studied in vitro, SS inhibited state 3 but stimulated state 4 of respiration, if alpha-ketoglutarate and succinate were used as the substrates. The inhibition of state 3 of respiration was not reversed by 2,4-dinitrophenol (DNP). Ph and APh inhibited the respiratory state 3 without affecting the state 4 in the presence of the same substrates, and the produced inhibition in state 3 was reversible by DNP. Studies on ATP synthesis have revealed that SS was the only antypyretic tested that exerted an uncoupling action. SS stimulated the mitochondrial ATPase activity but inhibited it after uncoupling of oxidative phosphorylation with DNP. The mitochondrial ATPase activity remained uninfluenced by Ph or APh. The only similar action of all the drugs investigated was the inhibition of oxidation in the respiratory state 3."}
{"id": "PMID:7776", "title": "Crystalline free radical of chloropromazine.", "content": "The method of preparation and the spectral characteristic of the crystalline free radical of chlorpromazine are described. Two absorption maxima at 770 and 860 nm concomitant with those at 530 and 277 nm were found. The highest rate of dismutation of the radical was 4-4.10(-1) M. sec-1 at pH 7-2. The mechanism of luminescence during the decay of the peroxide form of th radical is discussed.", "contents": "Crystalline free radical of chloropromazine. The method of preparation and the spectral characteristic of the crystalline free radical of chlorpromazine are described. Two absorption maxima at 770 and 860 nm concomitant with those at 530 and 277 nm were found. The highest rate of dismutation of the radical was 4-4.10(-1) M. sec-1 at pH 7-2. The mechanism of luminescence during the decay of the peroxide form of th radical is discussed."}
{"id": "PMID:7777", "title": "Kinetics of drug decomposition. Part 38. Hydrolysis and autoxidation of sodium phenylbutazone and aminophenazone in binary kinetic system.", "content": "The kinetics of hydrolysis and autoxidation of sodium phenylbutazone (PhB-Na) and aminophenazone (APh) was studied in ammonia-acetate, Carmody and Welford buffers at different buffer concentration, pH, ionic strengths and temperatures. The reaction in N2 atmosphere and under a constant O2 pressure, carried out in calibrated ampoules, followed the first order reaction kinetics. The assay of PhB-Na and APh in the presence of their degradation produces was carried out spectrophotometrically in the degraded solutions.", "contents": "Kinetics of drug decomposition. Part 38. Hydrolysis and autoxidation of sodium phenylbutazone and aminophenazone in binary kinetic system. The kinetics of hydrolysis and autoxidation of sodium phenylbutazone (PhB-Na) and aminophenazone (APh) was studied in ammonia-acetate, Carmody and Welford buffers at different buffer concentration, pH, ionic strengths and temperatures. The reaction in N2 atmosphere and under a constant O2 pressure, carried out in calibrated ampoules, followed the first order reaction kinetics. The assay of PhB-Na and APh in the presence of their degradation produces was carried out spectrophotometrically in the degraded solutions."}
{"id": "PMID:7781", "title": "The management of ulcerative colitis.", "content": "The modern medical and surgical treatment of ulcerative colitis has been detailed. Whilst improvements in medical management have been few in the past decade there have been advances in dietary management and in the use of new drugs such as azathioprine and disodium cromoglycate which are currently being evaluated. Sulphasalazine remains a valuable drug in treating attacks of the disease and in preventing relapses, and its mode of action is now better understood. Steroid therapy, used orally, parenterally or topically, is of value in managing acute colitic attacks. Surgery is often  required and total proctocolectomy with ileostomy remains the operation of choice. Colectomy with ileorectal anastomosis still remains a controversial operation but has its enthusiastic advocates. The interesting a new operation of proctocolectomy, with the establishment of an ileal bladder and continent ileostomy, is being assessed in Sweden and in a few centres in Britain and America.", "contents": "The management of ulcerative colitis. The modern medical and surgical treatment of ulcerative colitis has been detailed. Whilst improvements in medical management have been few in the past decade there have been advances in dietary management and in the use of new drugs such as azathioprine and disodium cromoglycate which are currently being evaluated. Sulphasalazine remains a valuable drug in treating attacks of the disease and in preventing relapses, and its mode of action is now better understood. Steroid therapy, used orally, parenterally or topically, is of value in managing acute colitic attacks. Surgery is often  required and total proctocolectomy with ileostomy remains the operation of choice. Colectomy with ileorectal anastomosis still remains a controversial operation but has its enthusiastic advocates. The interesting a new operation of proctocolectomy, with the establishment of an ileal bladder and continent ileostomy, is being assessed in Sweden and in a few centres in Britain and America."}
{"id": "PMID:7782", "title": "Purification, characterization, and quantitation of the antigen employed in the immunodiffusion test for diagnosis of equine infectious anemia.", "content": "Equine infectious anemia (EIA) antigen extracted from the spleen of horses infected with EIA virus was purified by pH treatment, (NH4)2SO4 fractionation and affinity chromatography. The homogeneity of the antigen was indicated by sedimentation rate and sedimentation equilibrium experiments. A S20,w of 0.51 was determined and a molecular weight of 7600 was calculated from sedimentation equilibrium analysis. The amino acid composition of the pure antigen indicated the antigen is an acidic protein. Employing radical immunodiffusion (RID) and pure antigen a method for quantitating antigen content of antigen containing preparations was developed.", "contents": "Purification, characterization, and quantitation of the antigen employed in the immunodiffusion test for diagnosis of equine infectious anemia. Equine infectious anemia (EIA) antigen extracted from the spleen of horses infected with EIA virus was purified by pH treatment, (NH4)2SO4 fractionation and affinity chromatography. The homogeneity of the antigen was indicated by sedimentation rate and sedimentation equilibrium experiments. A S20,w of 0.51 was determined and a molecular weight of 7600 was calculated from sedimentation equilibrium analysis. The amino acid composition of the pure antigen indicated the antigen is an acidic protein. Employing radical immunodiffusion (RID) and pure antigen a method for quantitating antigen content of antigen containing preparations was developed."}
{"id": "PMID:7783", "title": "Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione.", "content": "E. coli B tsnC 7004, an E. coli B/1 mutant with normal phenotype unable to replicate phage T7 DNA [Chamberlin, M. (1974)J. Virol. 14,509-516], contained no detectable level of thioredoxin when assayed with ribonucleotide reductase (2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1). Gently lysed E. coli tsnC 7004 cell extracts reduced CDP when supplemented with NADPH as efficiently as the parent strain E. coli B/1 despite the lack of thioredoxin, indicating the presence of another hydrogen transport system. This could be divided into two parts by heat treatment at 85degrees; one heat-stable fraction, which was active in the presence of dithiothreitol or glutathione, and one heat-labile fraction. Addition of yeast glutathione reductase [NAD(P)H:oxidized-glutathione oxidoreductase, EC 1.6.4.2] to the heated extracts restored full activity. The results demonstrate a novel hydrogen transport system in E. coli consisting of NADPH, glutathione, glutathione reductase, and a heat-stable enzyme called \"glutaredoxin\". Reduced glutathione at physiological concentrations functions as hydrogen donor for ribonucleotide reduction only in the presence of glutaredoxin. Glutaredoxin was not reduced by E. coli thioredoxin reductase (NADPH:oxidized-thioredoxin oxidoreductase, EC 1.6.4.5) and showed no crossreaction with antibodies against thioredoxin. These results demonstrate the existence of two different electron transfer systems from NADPH to deoxyribonucleotides and provide a function for glutathione in DNA synthesis.", "contents": "Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione. E. coli B tsnC 7004, an E. coli B/1 mutant with normal phenotype unable to replicate phage T7 DNA [Chamberlin, M. (1974)J. Virol. 14,509-516], contained no detectable level of thioredoxin when assayed with ribonucleotide reductase (2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1). Gently lysed E. coli tsnC 7004 cell extracts reduced CDP when supplemented with NADPH as efficiently as the parent strain E. coli B/1 despite the lack of thioredoxin, indicating the presence of another hydrogen transport system. This could be divided into two parts by heat treatment at 85degrees; one heat-stable fraction, which was active in the presence of dithiothreitol or glutathione, and one heat-labile fraction. Addition of yeast glutathione reductase [NAD(P)H:oxidized-glutathione oxidoreductase, EC 1.6.4.2] to the heated extracts restored full activity. The results demonstrate a novel hydrogen transport system in E. coli consisting of NADPH, glutathione, glutathione reductase, and a heat-stable enzyme called \"glutaredoxin\". Reduced glutathione at physiological concentrations functions as hydrogen donor for ribonucleotide reduction only in the presence of glutaredoxin. Glutaredoxin was not reduced by E. coli thioredoxin reductase (NADPH:oxidized-thioredoxin oxidoreductase, EC 1.6.4.5) and showed no crossreaction with antibodies against thioredoxin. These results demonstrate the existence of two different electron transfer systems from NADPH to deoxyribonucleotides and provide a function for glutathione in DNA synthesis."}
{"id": "PMID:7784", "title": "Dietary and hormonal regulation of the content of acetyl coenzyme A carboxylase-synthesizing polysomes in rat liver.", "content": "Specific polysomes involved the the synthesis of acetyl-CoA carboxylase [acetyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] have been identified by the binding of 125I-labeled antiacetyl-CoA carboxylase to rat liver polysomes. The binding is highly specific and occurs through the recognition of the nascent peptide chains on polysomes. With the use of the 125I-labeled antibody binding technique, it has been demonstrated that the relative content of acetyl-CoA carboxylase-synthesizing polysomes in the liver correlates well with the rate of hepatic synthesis of the enzyme in rats subjected to different dietary conditions as well as in alloxan-diabetic rats with or without insulin treatment.", "contents": "Dietary and hormonal regulation of the content of acetyl coenzyme A carboxylase-synthesizing polysomes in rat liver. Specific polysomes involved the the synthesis of acetyl-CoA carboxylase [acetyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] have been identified by the binding of 125I-labeled antiacetyl-CoA carboxylase to rat liver polysomes. The binding is highly specific and occurs through the recognition of the nascent peptide chains on polysomes. With the use of the 125I-labeled antibody binding technique, it has been demonstrated that the relative content of acetyl-CoA carboxylase-synthesizing polysomes in the liver correlates well with the rate of hepatic synthesis of the enzyme in rats subjected to different dietary conditions as well as in alloxan-diabetic rats with or without insulin treatment."}
{"id": "PMID:7785", "title": "gamma-Glutamyl transpeptidase, a lymphoid cell-surface marker: relationship to blastogenesis, differentiation, and neoplasia.", "content": "gamma-Glutamyl transpeptidase, an enzyme that catalyzes gamma-glutamyl transfer from gamma-glutamyl compounds to amino acid and peptide acceptors, and which is known to be localized in the membranes of many epithelial cells, was found in a variety of lymphoid cells. The lymphoid cell enzyme is located on the cell surface, and exhibits substantially the same substrate specificity as the enzyme found in epithelial cells. Human and rat (but not mouse) lymphocyte gamma-glutamyl transpeptidase was stimulated by treatment of the cells with mitogens. Normal human peripheral B-cells were more active than T-cells, but the reverse relationship of activities was found in chronic lymphocytic leukemia lymphocytes. Human lymphoblastic lines vary markedly in activity. In general, cell lines with B- and T-characteristics from patients with lymphoproliferative diseases had much lower activities than those of B-cell lines derived from normal subjects. The highest activity found was in a human myeloma line active in synthesis of an immunoglobulin light chain. The data indicate that gamma-glutamyl transpeptidase is a surface marker reflecting differentiation in normal and neoplastic cells.", "contents": "gamma-Glutamyl transpeptidase, a lymphoid cell-surface marker: relationship to blastogenesis, differentiation, and neoplasia. gamma-Glutamyl transpeptidase, an enzyme that catalyzes gamma-glutamyl transfer from gamma-glutamyl compounds to amino acid and peptide acceptors, and which is known to be localized in the membranes of many epithelial cells, was found in a variety of lymphoid cells. The lymphoid cell enzyme is located on the cell surface, and exhibits substantially the same substrate specificity as the enzyme found in epithelial cells. Human and rat (but not mouse) lymphocyte gamma-glutamyl transpeptidase was stimulated by treatment of the cells with mitogens. Normal human peripheral B-cells were more active than T-cells, but the reverse relationship of activities was found in chronic lymphocytic leukemia lymphocytes. Human lymphoblastic lines vary markedly in activity. In general, cell lines with B- and T-characteristics from patients with lymphoproliferative diseases had much lower activities than those of B-cell lines derived from normal subjects. The highest activity found was in a human myeloma line active in synthesis of an immunoglobulin light chain. The data indicate that gamma-glutamyl transpeptidase is a surface marker reflecting differentiation in normal and neoplastic cells."}
{"id": "PMID:7789", "title": "[Allergic vasculitis].", "content": "Cutaneous allergic vasculitis alone or combined with a systemic condition is of interest to the phlebologist when it occurs in the leg. All the clinical and paraclinical examinations must be oriented towards looking for infection, toxaemia, or even a so-called auto-immune disease. Treatment, although rarely very successful as regards the etiology, includes a considerable range of therapeutic possibilities, e.g. vasculotropic and anti-inflammatory drugs and immunosuppressive chemotherapy, to induce rapid sedation and often definitive cure.", "contents": "[Allergic vasculitis]. Cutaneous allergic vasculitis alone or combined with a systemic condition is of interest to the phlebologist when it occurs in the leg. All the clinical and paraclinical examinations must be oriented towards looking for infection, toxaemia, or even a so-called auto-immune disease. Treatment, although rarely very successful as regards the etiology, includes a considerable range of therapeutic possibilities, e.g. vasculotropic and anti-inflammatory drugs and immunosuppressive chemotherapy, to induce rapid sedation and often definitive cure."}
{"id": "PMID:7793", "title": "Economizing with psychotropic drugs.", "content": "Every health practitioner can reduce the cost of his treatments without compromising their quality. A review of the magnitude of the cost problem with regard to psychotropic drugs, variables which affect cost, the methods by which the clinician can manipulate the variables to reduce costs, and the application of these methods to the major classes of psychotropic drugs will show that substantial savings can be achieved easily and with no sacrifice in efficacy.", "contents": "Economizing with psychotropic drugs. Every health practitioner can reduce the cost of his treatments without compromising their quality. A review of the magnitude of the cost problem with regard to psychotropic drugs, variables which affect cost, the methods by which the clinician can manipulate the variables to reduce costs, and the application of these methods to the major classes of psychotropic drugs will show that substantial savings can be achieved easily and with no sacrifice in efficacy."}
{"id": "PMID:7791", "title": "Liver enzymatic induction after repeated or prolonged stress.", "content": "Changes in liver tyrosine aminotransferase induction were measured in mice after repeated or prolonged stressing. In the repeated chloroform stress variant the first impulse determines the amplitude of TAT induction; the second stress can only produce superinduction if repeated 40 minutes after the onset of the first one. In the prolonged irradiation stress variant the response was dependent on both the dose rate and duration of irradiation.", "contents": "Liver enzymatic induction after repeated or prolonged stress. Changes in liver tyrosine aminotransferase induction were measured in mice after repeated or prolonged stressing. In the repeated chloroform stress variant the first impulse determines the amplitude of TAT induction; the second stress can only produce superinduction if repeated 40 minutes after the onset of the first one. In the prolonged irradiation stress variant the response was dependent on both the dose rate and duration of irradiation."}
{"id": "PMID:7795", "title": "[Lithium tremor-combination treatment with beta receptor blockaders].", "content": "In addition to the various possibilities of influencing lithium tremor, experience gathered from the application of beta-receptor blockers is reported, and concepts investigated on the potential genesis and working mechanisms.", "contents": "[Lithium tremor-combination treatment with beta receptor blockaders]. In addition to the various possibilities of influencing lithium tremor, experience gathered from the application of beta-receptor blockers is reported, and concepts investigated on the potential genesis and working mechanisms."}
{"id": "PMID:7796", "title": "Intracranial self-stimulation in rats as a function of various stimulus parameters. VI. Influence of fentanyl, piritramide, and morphine on medial forebrain bundle stimulation with monopolar electrodes.", "content": "The effects of different subcutaneous doses of fentanyl (0.02, 0.04, 0.08, and 0.16 mg/kg), piritramide (0.63, 2.50, 10.0 and 40.0 mg/kg), and morphine (2.50, 5.00, 10.0 and 20.0 mg/kg) on self-stimulation in rats were studied. Different stimulus parameter combinations (SPC) inducing low, high or intermediate control response rates (CRR) were applied during the same experimental sessions. The three narcotic analgesics induced response depression (RD) and response stimulation (RS). RS was mostly observed at low dose levels; RD was dose-related. SPC's inducing low CRR were more sensitive than those inducing high CRR. Fentanyl was more potent than piritramide and than morphine. The RD is related to motor incapacitation, as the doses needed to effectively reduce self-stimulation also induced obvious catatonia. The RS probably is a more specific effect reflecting sensitization of structures involved in reinforcement of behavior.", "contents": "Intracranial self-stimulation in rats as a function of various stimulus parameters. VI. Influence of fentanyl, piritramide, and morphine on medial forebrain bundle stimulation with monopolar electrodes. The effects of different subcutaneous doses of fentanyl (0.02, 0.04, 0.08, and 0.16 mg/kg), piritramide (0.63, 2.50, 10.0 and 40.0 mg/kg), and morphine (2.50, 5.00, 10.0 and 20.0 mg/kg) on self-stimulation in rats were studied. Different stimulus parameter combinations (SPC) inducing low, high or intermediate control response rates (CRR) were applied during the same experimental sessions. The three narcotic analgesics induced response depression (RD) and response stimulation (RS). RS was mostly observed at low dose levels; RD was dose-related. SPC's inducing low CRR were more sensitive than those inducing high CRR. Fentanyl was more potent than piritramide and than morphine. The RD is related to motor incapacitation, as the doses needed to effectively reduce self-stimulation also induced obvious catatonia. The RS probably is a more specific effect reflecting sensitization of structures involved in reinforcement of behavior."}
{"id": "PMID:7797", "title": "[Wet dog shake behavior in normal rates, elicited by benzylideneaminooxycarbonic acid derivatives].", "content": "Wet dog shake (WDS) behavior in rats, well known as morphine-withdrawal syndrome, could be elicited without concomitant symptoms for the first time chemically in non-morphine-addicted animals. The capability to produce WDS was correlated with a specific chemical structure among the title-compounds. The threshold-dose of the most effective agents was 25-50 mg/kg, rather independent of the mode of application. Maximal response of 10-20 WDS per min and animal were reached after application of 100-200 mg/kg. WDS behavior appeared within the first minutes after dose and lasted up to several hours. Detailed information is given on WDS-action of the substance Sgd 8473 = alpha [(4chlorobenzylideneamino)-oxy]-isobutyric acid and the influence by different pharmacologie agents thereon. Inhibition of WDS was produced by: narcotic analgesics, narcotic antagonists, psychosedativ drugs, yohimbine, dl-amphetamine, cocaine, apomorphine and clonidine. Without influence on WDS were: physostigmine, atropine, ganglionic- or adrenergic-blocking drugs, Dopa, MAO-inhibitors, serotonin- and histamin-antagonists and nonnarcotic analgesics. To some extent chemically induced WDS seemed to be susceptible like precipitated WDS. So Sgd 8473 could be qualified for differentiating narctic analgesics, for a \"quasiabstinence\" agent in research of dependence mechanisms and for a tool in neuroanatomical studies of the CNS.", "contents": "[Wet dog shake behavior in normal rates, elicited by benzylideneaminooxycarbonic acid derivatives]. Wet dog shake (WDS) behavior in rats, well known as morphine-withdrawal syndrome, could be elicited without concomitant symptoms for the first time chemically in non-morphine-addicted animals. The capability to produce WDS was correlated with a specific chemical structure among the title-compounds. The threshold-dose of the most effective agents was 25-50 mg/kg, rather independent of the mode of application. Maximal response of 10-20 WDS per min and animal were reached after application of 100-200 mg/kg. WDS behavior appeared within the first minutes after dose and lasted up to several hours. Detailed information is given on WDS-action of the substance Sgd 8473 = alpha [(4chlorobenzylideneamino)-oxy]-isobutyric acid and the influence by different pharmacologie agents thereon. Inhibition of WDS was produced by: narcotic analgesics, narcotic antagonists, psychosedativ drugs, yohimbine, dl-amphetamine, cocaine, apomorphine and clonidine. Without influence on WDS were: physostigmine, atropine, ganglionic- or adrenergic-blocking drugs, Dopa, MAO-inhibitors, serotonin- and histamin-antagonists and nonnarcotic analgesics. To some extent chemically induced WDS seemed to be susceptible like precipitated WDS. So Sgd 8473 could be qualified for differentiating narctic analgesics, for a \"quasiabstinence\" agent in research of dependence mechanisms and for a tool in neuroanatomical studies of the CNS."}
{"id": "PMID:7798", "title": "Changes in excitability of amygdaloid and septal nuclei induced by medazepam hydrochloride.", "content": "Electrical stimulations of the central and basolateral part of the amygdaloid complex and of the septum in freely moving cats elicit changes in arterial pressure (i.e., an increase in pressure during stimulation of the central part of the amygdala, and a decrease followed by an increase during stimulation of the basolateral part of the amygdala and of the septum). These changes within the cardiovascular system are followed by rage reactions when the central part of the amygdala is stimulated, defense patterns when the basolateral part of the amygdala is stimulated, and pitiful mewing as a result of septal stimulation. Medazepam hydrochloride in a dose of approximately 15 mg/kg i.v. given over a period of 3 h, in order to maintain constant blood levels of the drug, attenuated slightly the cardiovascular reactions and elevated markedly the thresholds for psychomotoric behavior. The latencies between the onset of electrical stimulation and the beginning of the increase in arterial pressure were only slightly increased, whereas the latencies for spychomotoric behavior were markedly prolonged due to drug application. The data support the view that medazepam hydrochloride exerts depressant effects on the limbic-hypothalamic level with respect to psychomotoric responses. The effect was not identical for all nuclei tested. The basolateral part of the amygdala was significantly less sensitive to medazepam hydrochloride than the central part of the amygdala.", "contents": "Changes in excitability of amygdaloid and septal nuclei induced by medazepam hydrochloride. Electrical stimulations of the central and basolateral part of the amygdaloid complex and of the septum in freely moving cats elicit changes in arterial pressure (i.e., an increase in pressure during stimulation of the central part of the amygdala, and a decrease followed by an increase during stimulation of the basolateral part of the amygdala and of the septum). These changes within the cardiovascular system are followed by rage reactions when the central part of the amygdala is stimulated, defense patterns when the basolateral part of the amygdala is stimulated, and pitiful mewing as a result of septal stimulation. Medazepam hydrochloride in a dose of approximately 15 mg/kg i.v. given over a period of 3 h, in order to maintain constant blood levels of the drug, attenuated slightly the cardiovascular reactions and elevated markedly the thresholds for psychomotoric behavior. The latencies between the onset of electrical stimulation and the beginning of the increase in arterial pressure were only slightly increased, whereas the latencies for spychomotoric behavior were markedly prolonged due to drug application. The data support the view that medazepam hydrochloride exerts depressant effects on the limbic-hypothalamic level with respect to psychomotoric responses. The effect was not identical for all nuclei tested. The basolateral part of the amygdala was significantly less sensitive to medazepam hydrochloride than the central part of the amygdala."}
{"id": "PMID:7799", "title": "Hormonal influences of the extinction of conditioned taste aversion.", "content": "Conditioned taste aversion for a 5% glucose solution (sugar water) was induced in rats by an i.p. injection of LiCl 30 min after the first presentation of sugar water. Extinction of conditioned taste aversion was measured either in the forced-drinking test or in the preference-drinking test. In the forced-drinking test sugar water was the only fluid presented to the animals during extinction sessions. In the preference-drinking test the animals had the choice of tap water or sugar water. The rate of extinction was much slower in the preference test. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 7d Phe, and alpha-MSH delayed extinction in the preference test but not extinction in the forced-drinking test. ACTH 11-24 was without any effect. MSH-release inhibiting factor (MIF) facilitated extinction in the forced-drinking test but did not alter extinction in the preference test. The peptides did not affect intake of tap water of preference of sugar water over tap water by control rats.", "contents": "Hormonal influences of the extinction of conditioned taste aversion. Conditioned taste aversion for a 5% glucose solution (sugar water) was induced in rats by an i.p. injection of LiCl 30 min after the first presentation of sugar water. Extinction of conditioned taste aversion was measured either in the forced-drinking test or in the preference-drinking test. In the forced-drinking test sugar water was the only fluid presented to the animals during extinction sessions. In the preference-drinking test the animals had the choice of tap water or sugar water. The rate of extinction was much slower in the preference test. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 7d Phe, and alpha-MSH delayed extinction in the preference test but not extinction in the forced-drinking test. ACTH 11-24 was without any effect. MSH-release inhibiting factor (MIF) facilitated extinction in the forced-drinking test but did not alter extinction in the preference test. The peptides did not affect intake of tap water of preference of sugar water over tap water by control rats."}
{"id": "PMID:7800", "title": "Studies on the effects of histaminergic agents on seizure susceptibility in mice.", "content": "The influence of pharmacological modifications of the functional activity of the central histaminergic system was studied on the susceptibility of mice to pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures. Enhancement in the functional activity of the system by central administration of histamine or 4-methylhistamine of peripheral L-histidine loading failed to modify the risk of seizures. By contrast, reduction in histaminergic function was found to alter seizure susceptibility. Brocresine, an inhibitor of histamine synthesis, decreased and increased the risk of pentylenetetrazol-induced minimal and maximal seizures, respectively. Many, but not all, classical anti-histamines (H1 antagonist) and metiamide (H2 antagonist) and metiamide (H2 antagonist) increased minimal seizure susceptibility after periheral and intraventricular administration, respectively.", "contents": "Studies on the effects of histaminergic agents on seizure susceptibility in mice. The influence of pharmacological modifications of the functional activity of the central histaminergic system was studied on the susceptibility of mice to pentylenetetrazol-induced minimal (clonic) and maximal (tonic) seizures. Enhancement in the functional activity of the system by central administration of histamine or 4-methylhistamine of peripheral L-histidine loading failed to modify the risk of seizures. By contrast, reduction in histaminergic function was found to alter seizure susceptibility. Brocresine, an inhibitor of histamine synthesis, decreased and increased the risk of pentylenetetrazol-induced minimal and maximal seizures, respectively. Many, but not all, classical anti-histamines (H1 antagonist) and metiamide (H2 antagonist) and metiamide (H2 antagonist) increased minimal seizure susceptibility after periheral and intraventricular administration, respectively."}
{"id": "PMID:7802", "title": "[The treatment of polyphobic disturbances (author's transl)].", "content": "Clinically a combination of phenothiazine derivatives or thymoleptics with behavior-therapeutic techniques (systematic desensitation or assertive training) have proved effective in the treatment of polyphobic disturbances. Among the underlying theoretical considerations the level of activation achieves particular importance.", "contents": "[The treatment of polyphobic disturbances (author's transl)]. Clinically a combination of phenothiazine derivatives or thymoleptics with behavior-therapeutic techniques (systematic desensitation or assertive training) have proved effective in the treatment of polyphobic disturbances. Among the underlying theoretical considerations the level of activation achieves particular importance."}
{"id": "PMID:7807", "title": "Drug inhibition of ecto-ATPase and of phagocytosis in leukocytes.", "content": "Substituted phenothiazines and tricyclic antidepressants which inhibited the ecto-ATPase in leukocytes also markedly decreased the phagocytic activity of these cells. In affecting either the enzyme or phagocytosis the order of potency of the drugs was similar. Various other CNS drugs were ineffective. The results suggest possible involvement of ecto-ATPase in the phagocytic process, and indicate adverse effects of the aforelisted drugs on the host defense system against foreign materials, including microbes.", "contents": "Drug inhibition of ecto-ATPase and of phagocytosis in leukocytes. Substituted phenothiazines and tricyclic antidepressants which inhibited the ecto-ATPase in leukocytes also markedly decreased the phagocytic activity of these cells. In affecting either the enzyme or phagocytosis the order of potency of the drugs was similar. Various other CNS drugs were ineffective. The results suggest possible involvement of ecto-ATPase in the phagocytic process, and indicate adverse effects of the aforelisted drugs on the host defense system against foreign materials, including microbes."}
{"id": "PMID:7808", "title": "The excretion of phylloerythrin and bilirubin by calves and sheep.", "content": "Under general anaesthesia the common bile duct was ligated in two sheep and two calves. Occlusion of the duct was permanent and was followed by portal fibrosis, proliferation of bile ducts and intrahepatic bile stasis. Mild hepatic cell damage was accompanied by the release of glutamate dehydrogenase, sorbitol dehydrogenase and arginase into serum. The release of gamma-glutamyl transpeptidase was slower but more continuous. One sheep and one calf developed peritonitis associated with the leakage of bile from a biopsy wound in the live. One of these animals and the other two on which biopsy was not performed became photosensitised on exposure to sunlight. The concentration of phylloerythrin was high in serum and urine. All animals became jaundiced and the increased concentration of bilirubin in serum and urine was mainly direct reacting, ie, conjugated with glucuronic acid.", "contents": "The excretion of phylloerythrin and bilirubin by calves and sheep. Under general anaesthesia the common bile duct was ligated in two sheep and two calves. Occlusion of the duct was permanent and was followed by portal fibrosis, proliferation of bile ducts and intrahepatic bile stasis. Mild hepatic cell damage was accompanied by the release of glutamate dehydrogenase, sorbitol dehydrogenase and arginase into serum. The release of gamma-glutamyl transpeptidase was slower but more continuous. One sheep and one calf developed peritonitis associated with the leakage of bile from a biopsy wound in the live. One of these animals and the other two on which biopsy was not performed became photosensitised on exposure to sunlight. The concentration of phylloerythrin was high in serum and urine. All animals became jaundiced and the increased concentration of bilirubin in serum and urine was mainly direct reacting, ie, conjugated with glucuronic acid."}
{"id": "PMID:7834", "title": "Properties of Fcgamma receptors in normal and malignant human tissues.", "content": "Properties of the IgG receptors were studied by treating tissue sections or suspensions of peripheral mononuclear cells with various chemical reagents and determining changes in their ability to react with IgG-sensitized erythrocytes (EA). A heterogeneity of the Fc receptors was revealed. Iodoacetamide, 2-mercaptoethanol, sodium azide, EDTA, and a pH varying from 6.0 to 8.2 had no effect on Fc receptors in sections of normal lymphoreticular tissue and malignant tissue. Formaldehyde, low pH, and high salt concentrations affected receptor activity to various degrees. Receptors in liver sections and on monocytes were generally more resistant than receptors in spleen sections and on B lymphocytes. Receptors in malignant tissue behaved either like receptors in spleen or like receptors in liver. Although all tissues were sensitive to periodic acid, the Fc receptors in malignant tissue were always more resistant.", "contents": "Properties of Fcgamma receptors in normal and malignant human tissues. Properties of the IgG receptors were studied by treating tissue sections or suspensions of peripheral mononuclear cells with various chemical reagents and determining changes in their ability to react with IgG-sensitized erythrocytes (EA). A heterogeneity of the Fc receptors was revealed. Iodoacetamide, 2-mercaptoethanol, sodium azide, EDTA, and a pH varying from 6.0 to 8.2 had no effect on Fc receptors in sections of normal lymphoreticular tissue and malignant tissue. Formaldehyde, low pH, and high salt concentrations affected receptor activity to various degrees. Receptors in liver sections and on monocytes were generally more resistant than receptors in spleen sections and on B lymphocytes. Receptors in malignant tissue behaved either like receptors in spleen or like receptors in liver. Although all tissues were sensitive to periodic acid, the Fc receptors in malignant tissue were always more resistant."}
{"id": "PMID:7836", "title": "Induction of tyrosine 3-monooxygenase in adrenal medulla: role of protein kinase activation and translocation.", "content": "The transsynaptic induction of tyrosine 3-monooxygenase (TH) in rat adrenal medulla is preceded by an early increase in the ratio of cyclic adenosine monophosphate (AMP) to cyclic guanosine monophosphate, an activation of cytosol cyclic AMP-dependent protein kinase, and a subsequent translocation of protein kinase catalytic subunits from cytosol to subcellular particles. As a result of this translocation, nuclear protein kinase activity increases during the induction of TH. Transection of splanchnic nerve reverts these events and prevents the induction of TH. Thus, adrenal medulla activation and translocation of cyclic AMP-dependent protein kinase may act as a long-range messenger for the genetic regulation of TH synthesis.", "contents": "Induction of tyrosine 3-monooxygenase in adrenal medulla: role of protein kinase activation and translocation. The transsynaptic induction of tyrosine 3-monooxygenase (TH) in rat adrenal medulla is preceded by an early increase in the ratio of cyclic adenosine monophosphate (AMP) to cyclic guanosine monophosphate, an activation of cytosol cyclic AMP-dependent protein kinase, and a subsequent translocation of protein kinase catalytic subunits from cytosol to subcellular particles. As a result of this translocation, nuclear protein kinase activity increases during the induction of TH. Transection of splanchnic nerve reverts these events and prevents the induction of TH. Thus, adrenal medulla activation and translocation of cyclic AMP-dependent protein kinase may act as a long-range messenger for the genetic regulation of TH synthesis."}
{"id": "PMID:7837", "title": "Calcium-independent modulation of cyclic GMP and activation of guanylate cyclase by nitrosamines.", "content": "Nitrosamines markedly increase concentrations of guanosine 3', 5' - monophosphate (cyclic GMP) in several tissues from the rat and in human colonic mucosa. These agents are effective in the absence of extracellular calcium and enhance guanylate cyclase activity in tissue homogenates. Stimulation of cyclic GMP was greatest in liver, where the carcinogenic activity of nitrosamines is also most pronounced.", "contents": "Calcium-independent modulation of cyclic GMP and activation of guanylate cyclase by nitrosamines. Nitrosamines markedly increase concentrations of guanosine 3', 5' - monophosphate (cyclic GMP) in several tissues from the rat and in human colonic mucosa. These agents are effective in the absence of extracellular calcium and enhance guanylate cyclase activity in tissue homogenates. Stimulation of cyclic GMP was greatest in liver, where the carcinogenic activity of nitrosamines is also most pronounced."}
{"id": "PMID:7838", "title": "Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat.", "content": "Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.", "contents": "Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat. Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles."}
{"id": "PMID:7839", "title": "Modulation of synaptic transmitter release by repetitive postsynaptic action potentials.", "content": "The effect of repetitive action potentials in the postsynaptic axon on the release of synaptic transmitter from the presynaptic terminal was investigated at the squid giant synapse. Repetitive antidromic stimulation of the postsynaptic axon resulted in a reduction in the excitatory postsynaptic potential (EPSP). The reduction in transmitter release was accompanied by a decrease in the presynaptic spike after-hyperpolarization (AH). Increasing the concentration of extracellular potassium ions also reduced the EPSP and decreased the amplitude of the presynaptic spike AH. The reduction in transmitter release resulting from repetitive postsynaptic impulses is attributed to the accumulation of extracellular potassium ions. It is proposed that the accumulation of extracellular potassium ions resulting from repetitive postsynaptic activity may modulate synaptic transmission and function as an integrative mechanism in the nervous system.", "contents": "Modulation of synaptic transmitter release by repetitive postsynaptic action potentials. The effect of repetitive action potentials in the postsynaptic axon on the release of synaptic transmitter from the presynaptic terminal was investigated at the squid giant synapse. Repetitive antidromic stimulation of the postsynaptic axon resulted in a reduction in the excitatory postsynaptic potential (EPSP). The reduction in transmitter release was accompanied by a decrease in the presynaptic spike after-hyperpolarization (AH). Increasing the concentration of extracellular potassium ions also reduced the EPSP and decreased the amplitude of the presynaptic spike AH. The reduction in transmitter release resulting from repetitive postsynaptic impulses is attributed to the accumulation of extracellular potassium ions. It is proposed that the accumulation of extracellular potassium ions resulting from repetitive postsynaptic activity may modulate synaptic transmission and function as an integrative mechanism in the nervous system."}
{"id": "PMID:7840", "title": "Laryngeal microsurgery without intubation.", "content": "Reviewed are 200 cases in which endolaryngeal suspension microsurgical procedures were done using intravenous anesthesia and Venturi insufflation oxygenation. Patients included 177 adults and 23 children, ranging in age from 20 months to 88 years. No significant complications were observed. The technic allowed the glottic space to remain free of cumbersome intraluminal apparatus. Arterial blood studies revealed that adequate oxygenation is achieved while normal pH and PaCO2 levels are maintained.", "contents": "Laryngeal microsurgery without intubation. Reviewed are 200 cases in which endolaryngeal suspension microsurgical procedures were done using intravenous anesthesia and Venturi insufflation oxygenation. Patients included 177 adults and 23 children, ranging in age from 20 months to 88 years. No significant complications were observed. The technic allowed the glottic space to remain free of cumbersome intraluminal apparatus. Arterial blood studies revealed that adequate oxygenation is achieved while normal pH and PaCO2 levels are maintained."}
{"id": "PMID:7841", "title": "Food-drug interactions and interference.", "content": "Examples are given of interactions between foods and drugs, some of which may on occasion produce adverse effects. Such interactions are not as frequent and rarely as significant as interactions between drugs, which have become of increasing interest and importance.", "contents": "Food-drug interactions and interference. Examples are given of interactions between foods and drugs, some of which may on occasion produce adverse effects. Such interactions are not as frequent and rarely as significant as interactions between drugs, which have become of increasing interest and importance."}
{"id": "PMID:7843", "title": "Granulomatous glomerulonephritis and fulminant polyarteritis nodosa in a child.", "content": "The clinical and histological findings in a 12-year-old Black child with microscopic polyarteritis nodosa are presented. Particular attention is drawn to the unusual appearance of granulomatous glomerulonephritis.", "contents": "Granulomatous glomerulonephritis and fulminant polyarteritis nodosa in a child. The clinical and histological findings in a 12-year-old Black child with microscopic polyarteritis nodosa are presented. Particular attention is drawn to the unusual appearance of granulomatous glomerulonephritis."}
{"id": "PMID:7844", "title": "Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery.", "content": "In vitro experiments were performed using a small volume chamber to determine the contractile activity of several adrenergic agents on arteries from six locations of the canine vascular bed. Cumulative log-dose response curves were obtained for epinephrine, norepinephrine, phenylephrine and dopamine. It was found that the basilar and internal carotid arteries responded much less to these agents than did the mesenteric, renal and femoral arteries. Six blocking agents including nitroprusside were tested to determine their effect on the response of the canine basilar artery to log-dose additions of serotonin, prostaglandin F2alpha and KC1. Another chamber was developed to study the differential effect of nitroprusside and papaverine when placed on the luminal side versus the adventitial (cerebrospinal fluid) side of the basilar artery during a sustained contraction with serotonin. A theoretical treatment of cerebral arterial spasm following a subarachnoid hemorrhage is presented.", "contents": "Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery. In vitro experiments were performed using a small volume chamber to determine the contractile activity of several adrenergic agents on arteries from six locations of the canine vascular bed. Cumulative log-dose response curves were obtained for epinephrine, norepinephrine, phenylephrine and dopamine. It was found that the basilar and internal carotid arteries responded much less to these agents than did the mesenteric, renal and femoral arteries. Six blocking agents including nitroprusside were tested to determine their effect on the response of the canine basilar artery to log-dose additions of serotonin, prostaglandin F2alpha and KC1. Another chamber was developed to study the differential effect of nitroprusside and papaverine when placed on the luminal side versus the adventitial (cerebrospinal fluid) side of the basilar artery during a sustained contraction with serotonin. A theoretical treatment of cerebral arterial spasm following a subarachnoid hemorrhage is presented."}
{"id": "PMID:7845", "title": "Adrenergic blockade and renal hemodynamics.", "content": "An isolated blood perfused kidney preparation was used to study the influence of intrarenal adrenergic receptors on renal hemodynamics, renal function, and the renin-angiotensin system. Beta adrenergic blockade with propranolol resulted in a reduction of fractional sodium excretion, and alpha blockade with phentolamine had no effect on sodium excretion despite significant increases in cortical flow and glomerular filtration rate. The changes in sodium excretion after beta blockade were not felt to be due to a direct tubular effect but rather were secondary to preferential perfusion of nephrons in the juxtamedullary cortex, which is known to have higher sodium reabsorptive capacity. These changes appeared to be direct effects of adrenergic blockade on the renal vasculature and were independent of any effects on renin secretion.", "contents": "Adrenergic blockade and renal hemodynamics. An isolated blood perfused kidney preparation was used to study the influence of intrarenal adrenergic receptors on renal hemodynamics, renal function, and the renin-angiotensin system. Beta adrenergic blockade with propranolol resulted in a reduction of fractional sodium excretion, and alpha blockade with phentolamine had no effect on sodium excretion despite significant increases in cortical flow and glomerular filtration rate. The changes in sodium excretion after beta blockade were not felt to be due to a direct tubular effect but rather were secondary to preferential perfusion of nephrons in the juxtamedullary cortex, which is known to have higher sodium reabsorptive capacity. These changes appeared to be direct effects of adrenergic blockade on the renal vasculature and were independent of any effects on renin secretion."}
{"id": "PMID:7862", "title": "Reactivation studies of an affinity labeled steroid oxido-reductase. I. Inactivation of 20 beta-hydroxysteroid dehydrogenase with 6 beta-bromoacetoxyprogesterone vs 6 beta-bromoprogesterone.", "content": "20 beta-Hydroxysteroid dehydrogenase (E.C. 1.1.1.53), which had been completely inactivated with 6beta-bromoacetoxyprogesterone at pH 7.0, was reactivated by elevating the pH. The rate of reactivation is pH dependant, characteristic of base-catalysed ester hydrolysis. Similar experiments with 6beta-bromoprogesterone fail to produce reactivation of the affinity labeled enzyme. Formation and scission of different types of covalent bonds during affinity labeling and reactivation attempts accounts for the different result obtained with each steroid. The activity of the reactivated steroid oxido-reductase vs the native enzyme, and also substrate stabilization of the enzyme are discussed.", "contents": "Reactivation studies of an affinity labeled steroid oxido-reductase. I. Inactivation of 20 beta-hydroxysteroid dehydrogenase with 6 beta-bromoacetoxyprogesterone vs 6 beta-bromoprogesterone. 20 beta-Hydroxysteroid dehydrogenase (E.C. 1.1.1.53), which had been completely inactivated with 6beta-bromoacetoxyprogesterone at pH 7.0, was reactivated by elevating the pH. The rate of reactivation is pH dependant, characteristic of base-catalysed ester hydrolysis. Similar experiments with 6beta-bromoprogesterone fail to produce reactivation of the affinity labeled enzyme. Formation and scission of different types of covalent bonds during affinity labeling and reactivation attempts accounts for the different result obtained with each steroid. The activity of the reactivated steroid oxido-reductase vs the native enzyme, and also substrate stabilization of the enzyme are discussed."}
{"id": "PMID:7863", "title": "Mitigation of graft-versus-host disease in lethally irradiated mice grafted with spleen cells adherent to glass beads.", "content": "Murine spleen cells were separated on the basis of adherence to glass beads into distinct subpopulations that differ in their ability to produce acute graft-versus-host disease (GVHD). Nonadherent CBA spleen cells produce acute GVHD in 6-10 days in lethally irradiated (C57BL/6 X CBA)F1 mice as do unfractionated spleen cells. Spleen cells which are adherent to glass beads, however, enable 71% of the mice to survive without symptomatology of acute GVHD. The low proliferative response of these cells to phytohemagglutinin (PHA) correlated with the mitigated GVHD seen in animals grafted with this fraction. Proliferative cells as determined by the spleen colony assay and the in vitro agar colony-forming assay are present in this fraction as are cells responsive to mitogenic stimulation with lipopolysaccharide (LPS). B6CBF1 mice grafted with CBA adherent cells exhibit a gradual return over a period of 5 months to normal PHA and LPS stimulation levels as shown by splenic cell responses of these mice to mitogens. Surviving mice grafted with adherent cells were chimeric as determined by electrophoretic hemoglobin pattern analysis and serial bone marrow transplantation.", "contents": "Mitigation of graft-versus-host disease in lethally irradiated mice grafted with spleen cells adherent to glass beads. Murine spleen cells were separated on the basis of adherence to glass beads into distinct subpopulations that differ in their ability to produce acute graft-versus-host disease (GVHD). Nonadherent CBA spleen cells produce acute GVHD in 6-10 days in lethally irradiated (C57BL/6 X CBA)F1 mice as do unfractionated spleen cells. Spleen cells which are adherent to glass beads, however, enable 71% of the mice to survive without symptomatology of acute GVHD. The low proliferative response of these cells to phytohemagglutinin (PHA) correlated with the mitigated GVHD seen in animals grafted with this fraction. Proliferative cells as determined by the spleen colony assay and the in vitro agar colony-forming assay are present in this fraction as are cells responsive to mitogenic stimulation with lipopolysaccharide (LPS). B6CBF1 mice grafted with CBA adherent cells exhibit a gradual return over a period of 5 months to normal PHA and LPS stimulation levels as shown by splenic cell responses of these mice to mitogens. Surviving mice grafted with adherent cells were chimeric as determined by electrophoretic hemoglobin pattern analysis and serial bone marrow transplantation."}
{"id": "PMID:7864", "title": "Marrow grafts between canine litter-mates homozygous or heterozygous for lymphocyte-defined histocompatibility antigens.", "content": "Hemopoietic grafts following 1,200 R of total body irradiation were carried out between canine littermates homozygous or heterozygous for lymphocyte defined (LD) antigens of the major histocompatibility complex (MHC). In all but five of the 25 pairs studied, LD homozygous dogs were also homozygous for serologically defined (SD) antigens of the MHC. Results of transplants were compared with previous results obtained in littermate pairs matched or mismatched for the MHC. Two groups of recipients were studied. Of 14 LD homozygous recipients in group 1 given grafts from LD heterozygous donors, 12 died between 8 and 193 days and two survived more than 238 and 627 days. The most frequent cause of death was graft-versus-host disease (GVHD). Survival was significantly shorter (P less than 0.005) than that of dogs given grafts from matched littermates and not different (P congruent to 0.5) from that of dogs given grafts from mismatched littermates. Survival of 11 LD heterozygous recipients in group 2 given grafts from LD homozygous donors was not different from that of dogs in group 1 (P congruent to 0.5). The results indicate that the LD loci detected by mixed leukocyte culture are not the principal determinants within the MHC that are responsible for GVHD.", "contents": "Marrow grafts between canine litter-mates homozygous or heterozygous for lymphocyte-defined histocompatibility antigens. Hemopoietic grafts following 1,200 R of total body irradiation were carried out between canine littermates homozygous or heterozygous for lymphocyte defined (LD) antigens of the major histocompatibility complex (MHC). In all but five of the 25 pairs studied, LD homozygous dogs were also homozygous for serologically defined (SD) antigens of the MHC. Results of transplants were compared with previous results obtained in littermate pairs matched or mismatched for the MHC. Two groups of recipients were studied. Of 14 LD homozygous recipients in group 1 given grafts from LD heterozygous donors, 12 died between 8 and 193 days and two survived more than 238 and 627 days. The most frequent cause of death was graft-versus-host disease (GVHD). Survival was significantly shorter (P less than 0.005) than that of dogs given grafts from matched littermates and not different (P congruent to 0.5) from that of dogs given grafts from mismatched littermates. Survival of 11 LD heterozygous recipients in group 2 given grafts from LD homozygous donors was not different from that of dogs in group 1 (P congruent to 0.5). The results indicate that the LD loci detected by mixed leukocyte culture are not the principal determinants within the MHC that are responsible for GVHD."}
{"id": "PMID:7865", "title": "Transplantation of hematopoietic and lymphoid cells in mice.", "content": "CBA mice were exposed to a supralethal dose of whole body X-irradiation and recieved transplants of graded, small doses of bone marrow, fetal liver, or fetal liver plus fetal thymus cells obtained from H-2 matched C58 or H-2 mismatched A donors. Survival at 20 days was used to evaluate the ability of the transplants to restore hematopoiesis following the acute radiation injury. In the higher dose ranges of 6 X 10(7) and 1.2 X 10(8) cells/kg body weight, the fetal cells were as effective as adult bone marrow in both the matched and mismatched strain combinations. Survival at 100 days was used to evaluate the severity of chronic graft-versus-host disease produced by each of the transplants. In the higher dose ranges, cells from fetal donors promoted higher long-term survival rates than did comparable doses of bone marrow cells in both the matched and mismatched strain combinations. In some experimental groups, the addition of fetal thymus cells to fetal liver cells resulted in higher short-term and long-term survival rates than did fetal liver alone, but this was inconsistent and generally fell short of statistical significance. The most important finding was that cells from mismatched unrelated fetal donors (using a cell dose per kilogram body weight comparable to the number of fetal liver and thymus cells which would be obtainable from one human fetus at 14 weeks of embryonation) promoted higher long-term survival rates than did bone marrow transplants from matched unrelated donors.", "contents": "Transplantation of hematopoietic and lymphoid cells in mice. CBA mice were exposed to a supralethal dose of whole body X-irradiation and recieved transplants of graded, small doses of bone marrow, fetal liver, or fetal liver plus fetal thymus cells obtained from H-2 matched C58 or H-2 mismatched A donors. Survival at 20 days was used to evaluate the ability of the transplants to restore hematopoiesis following the acute radiation injury. In the higher dose ranges of 6 X 10(7) and 1.2 X 10(8) cells/kg body weight, the fetal cells were as effective as adult bone marrow in both the matched and mismatched strain combinations. Survival at 100 days was used to evaluate the severity of chronic graft-versus-host disease produced by each of the transplants. In the higher dose ranges, cells from fetal donors promoted higher long-term survival rates than did comparable doses of bone marrow cells in both the matched and mismatched strain combinations. In some experimental groups, the addition of fetal thymus cells to fetal liver cells resulted in higher short-term and long-term survival rates than did fetal liver alone, but this was inconsistent and generally fell short of statistical significance. The most important finding was that cells from mismatched unrelated fetal donors (using a cell dose per kilogram body weight comparable to the number of fetal liver and thymus cells which would be obtainable from one human fetus at 14 weeks of embryonation) promoted higher long-term survival rates than did bone marrow transplants from matched unrelated donors."}
{"id": "PMID:7866", "title": "[Dinitroorthocresol dissociation of oxidative phosphorylation in the rat liver perfused in situ].", "content": "Perfusion of the rat liver in situ for 150 min provides for maintaining optimal values of acid-base balance for the following indexes: surplus of bases, content of standard bicarbonate, buffer bases pH, pO2, pCO2, HbO2, the level of bile secretion, content of lactate, pyruvate, ATP, ADP, that evidences for a high functional activity in the tissue. Introduction of dinitro-ortho-cresol (DNC) into the perfusion liquid causes development of acidosis. DNC results in dissociation of oxidative phosphorylation: the content of ATP and intensity of inorganic phosphorus utilization decrease, oxygen uptake intensifies. A compensatory increase in the glycolysis intensity directed to maintaining the level of macroergs under these conditions is is pronounced in the intensified uptake of glucose, in a rise in the content of lactate in perfusate and an increase in the pyruvate kinase activity in the liver. The redox state of NAD-pairs (ratio of [NAD+] : [NADN] calculated from the content of redox metabolites and the equilibrium constant for the lactate dehydrogenase system shifts toward an increase in the reducing properties of hepatocytes cytoplasm. The phosphate potential value calculated from the ratio [ATP] : [ADP] - [Pinor] lowers under conditions of the experiment.", "contents": "[Dinitroorthocresol dissociation of oxidative phosphorylation in the rat liver perfused in situ]. Perfusion of the rat liver in situ for 150 min provides for maintaining optimal values of acid-base balance for the following indexes: surplus of bases, content of standard bicarbonate, buffer bases pH, pO2, pCO2, HbO2, the level of bile secretion, content of lactate, pyruvate, ATP, ADP, that evidences for a high functional activity in the tissue. Introduction of dinitro-ortho-cresol (DNC) into the perfusion liquid causes development of acidosis. DNC results in dissociation of oxidative phosphorylation: the content of ATP and intensity of inorganic phosphorus utilization decrease, oxygen uptake intensifies. A compensatory increase in the glycolysis intensity directed to maintaining the level of macroergs under these conditions is is pronounced in the intensified uptake of glucose, in a rise in the content of lactate in perfusate and an increase in the pyruvate kinase activity in the liver. The redox state of NAD-pairs (ratio of [NAD+] : [NADN] calculated from the content of redox metabolites and the equilibrium constant for the lactate dehydrogenase system shifts toward an increase in the reducing properties of hepatocytes cytoplasm. The phosphate potential value calculated from the ratio [ATP] : [ADP] - [Pinor] lowers under conditions of the experiment."}
{"id": "PMID:7875", "title": "[Development and resistance of staphylococci in Bulgaricus milk].", "content": "Studied was the dynamics of development of 9 strains of staphilococci isolated from humans and animals, kept in heat-treated milk, and their resistance in Bulgarian sour milk. It was established that the pathogenic Staph. aureus and  Staph. epidermidis develop will in fresh milk kept up to 7 days at 2--6degreesC and 18--22degreesC. In the production of Bulgarian sour milk Staph, aureus was shown to be viable, remaining active for seven days at 2 to 6degreesC. At room temperature (18--22degreesC) the survival rate has been dependent on the dynamics of accumulating metabolite products in connection with the development of Lactobac. bulgaricum and Streptococcus thermophilus. When the total acidity value reaches 160degreesT the pathogenic staphylococci are destroyed. Staphylococcus epidermidis finds no favourable medium to develop in Bulgarian sour milk, and it perishes when the total acidity is 120degreesT and pH -- 3.", "contents": "[Development and resistance of staphylococci in Bulgaricus milk]. Studied was the dynamics of development of 9 strains of staphilococci isolated from humans and animals, kept in heat-treated milk, and their resistance in Bulgarian sour milk. It was established that the pathogenic Staph. aureus and  Staph. epidermidis develop will in fresh milk kept up to 7 days at 2--6degreesC and 18--22degreesC. In the production of Bulgarian sour milk Staph, aureus was shown to be viable, remaining active for seven days at 2 to 6degreesC. At room temperature (18--22degreesC) the survival rate has been dependent on the dynamics of accumulating metabolite products in connection with the development of Lactobac. bulgaricum and Streptococcus thermophilus. When the total acidity value reaches 160degreesT the pathogenic staphylococci are destroyed. Staphylococcus epidermidis finds no favourable medium to develop in Bulgarian sour milk, and it perishes when the total acidity is 120degreesT and pH -- 3."}
{"id": "PMID:7876", "title": "[Nonspecific aortoarteriitis (Takayasu's disease) (author's transl)].", "content": "Histology of 10 certified and 5 possible cases of nonspecific aortoarteriitis (Takayasu's disease) is described. The lesions are not specific. They consist of diffuse or focal chronic inflammatory infiltrates in media and adventita. Granulomas with or without central coagulation necrosis may occur. Media and adventitia show a marked fibrous hyperplasia. The elastic fibers are destroyed. The intima is thickened by a fibrous proliferation. Secondary arteriosclerosis is frequently observed. Perforated or dissecting aneurysms due to the chronic inflammation of the aortic wall may occur. The abdominal aorta is most frequently affected, but any section of the aortic wall may be involved. Takayasu's disease is not rare in our area. Contrary to most of the tropical countries, females do not predominate among our patients and aged persons may be affected, too. Etiology is unknown, the affection probably belongs to the autoimmune diseases. The histologic differentiation from other inflammatory vascular diseases and even from a resorptive inflammation due to a perforated or dissected aneurysm may be extremely difficult.", "contents": "[Nonspecific aortoarteriitis (Takayasu's disease) (author's transl)]. Histology of 10 certified and 5 possible cases of nonspecific aortoarteriitis (Takayasu's disease) is described. The lesions are not specific. They consist of diffuse or focal chronic inflammatory infiltrates in media and adventita. Granulomas with or without central coagulation necrosis may occur. Media and adventitia show a marked fibrous hyperplasia. The elastic fibers are destroyed. The intima is thickened by a fibrous proliferation. Secondary arteriosclerosis is frequently observed. Perforated or dissecting aneurysms due to the chronic inflammation of the aortic wall may occur. The abdominal aorta is most frequently affected, but any section of the aortic wall may be involved. Takayasu's disease is not rare in our area. Contrary to most of the tropical countries, females do not predominate among our patients and aged persons may be affected, too. Etiology is unknown, the affection probably belongs to the autoimmune diseases. The histologic differentiation from other inflammatory vascular diseases and even from a resorptive inflammation due to a perforated or dissected aneurysm may be extremely difficult."}
{"id": "PMID:7907", "title": "[alpha-Hemolysin of E. coli].", "content": "The activity of alpha-hemolysin increased at the log growth phase in the culture of E. coli P678 Hly+ hemolytic strain; this activity diminished with the change into the stationary phase, and then fell sharply. Replacement of the culture medium in the stationary growth phase by fresh one led to restoration of the hemolytic activity of the culture. The culture fluid separated from the cells at the stationary growth phase produced an inhibitory action on the alpha-hemolysin Ca ions activated and stabilized the alpha-hemolysin. Sodium citrate and sucrose served as hemolysis inhibitors. The action of alpha-hemolysin was maximal against human erythrocytes at pH 6.5. Hemolytic activity was characterized in time by a distinct lag-phase and the phase of the greatest rate of reaction. The duration of the lag-phase and also the rate of hemolysis depended on the concentration of alpha-hemolysin (with the increase of the hemolysin concentration lag-phase was shortened and the reaction was accelerated). There proved to be a linear relationship between the amount of erythrocytes taken into the reaction and the rate of hemoglobin release, and also there was noted a temperature activation of the hemolytic reaction.", "contents": "[alpha-Hemolysin of E. coli]. The activity of alpha-hemolysin increased at the log growth phase in the culture of E. coli P678 Hly+ hemolytic strain; this activity diminished with the change into the stationary phase, and then fell sharply. Replacement of the culture medium in the stationary growth phase by fresh one led to restoration of the hemolytic activity of the culture. The culture fluid separated from the cells at the stationary growth phase produced an inhibitory action on the alpha-hemolysin Ca ions activated and stabilized the alpha-hemolysin. Sodium citrate and sucrose served as hemolysis inhibitors. The action of alpha-hemolysin was maximal against human erythrocytes at pH 6.5. Hemolytic activity was characterized in time by a distinct lag-phase and the phase of the greatest rate of reaction. The duration of the lag-phase and also the rate of hemolysis depended on the concentration of alpha-hemolysin (with the increase of the hemolysin concentration lag-phase was shortened and the reaction was accelerated). There proved to be a linear relationship between the amount of erythrocytes taken into the reaction and the rate of hemoglobin release, and also there was noted a temperature activation of the hemolytic reaction."}
{"id": "PMID:7908", "title": "[Comparative study of the proteinograms of vibrios and of closely related microorganisms by means of polyacrylamide gel disc electrophoresis].", "content": "Proteinograms of 112 strains of vibrios and closely affiliated microorganisms were studied by disc electrophoresis in polyacrylamide gel. Up to 25 protein peaks with definite mobility coefficients were revealed. The influence of the culture medium on the protein spectrum of the microbes was found. The frequency of peak formation was of great significance for the differentiation of the microbes under study. The quantitative characteristics of the peak area could not be used for differentiation.", "contents": "[Comparative study of the proteinograms of vibrios and of closely related microorganisms by means of polyacrylamide gel disc electrophoresis]. Proteinograms of 112 strains of vibrios and closely affiliated microorganisms were studied by disc electrophoresis in polyacrylamide gel. Up to 25 protein peaks with definite mobility coefficients were revealed. The influence of the culture medium on the protein spectrum of the microbes was found. The frequency of peak formation was of great significance for the differentiation of the microbes under study. The quantitative characteristics of the peak area could not be used for differentiation."}
{"id": "PMID:7909", "title": "[Dynamics of mental disorders in poisoning with hypnotic and sedative preparations].", "content": "In order to study some mental disorders due to poisoning by sleeping and sedative drugs 258 patients with mental and boderline conditions (who had taken these drugs in toxic doses) were studied in the Sklifosovskiy Moscow Research Institute of Emergency Medical Aid. The revealed mental disorders on different stages of poisoning were less differentiated in the acute period (clouded consciousness, coma) and most diverse in pre- and postcomatose stages, where they were characterized by disturbed consciousness, hallucinatory and delusional experiences, epileptiformal syndromes, emotional, motor and other disturbances. The symptomatology depended upon the type of medical drug, intensity of medical procedures, the mental or boderline disease itself which influences the clinical picture of every stage of the intoxication.", "contents": "[Dynamics of mental disorders in poisoning with hypnotic and sedative preparations]. In order to study some mental disorders due to poisoning by sleeping and sedative drugs 258 patients with mental and boderline conditions (who had taken these drugs in toxic doses) were studied in the Sklifosovskiy Moscow Research Institute of Emergency Medical Aid. The revealed mental disorders on different stages of poisoning were less differentiated in the acute period (clouded consciousness, coma) and most diverse in pre- and postcomatose stages, where they were characterized by disturbed consciousness, hallucinatory and delusional experiences, epileptiformal syndromes, emotional, motor and other disturbances. The symptomatology depended upon the type of medical drug, intensity of medical procedures, the mental or boderline disease itself which influences the clinical picture of every stage of the intoxication."}
{"id": "PMID:7911", "title": "Alpha-N-Benzoylarginine-2-naphthylamide hydrolase (cathepsin BI?) from rat skin. III. Substrate specificity, modifier characteristics, and transformation of the enzyme at acidic pH.", "content": "Some properties of rat skin benzoylarginine-2-naphthylamide hydrolase types I (preparations I and AI) and II (preparations II and NII) were studied. Both types were activated by dithiothreitol and EDTA, but responded differently to 1 mM KCN, when benzoylarginine-2-naphthylamide (BANA) was used as a substrate: type I was inhibited, while type II was activated. When leucine-2-naphthylamide was used as a substrate, both types were activated by KCN. Thiol proteinase inhibiting substances, like heavy metals, iodoacetic acid, 4-chloromercuribenzoic acid, and tosyllysine chloromethylketone, inhibited the enzymes. Diisopropylfluorophosphate, phenylmethylsulfonyfluoride, 4-aminobenzamidine, and high-molecular-weight trypsin inhibitors were without effect. The substrate specificity of rat skin BANA hydrolase resembled that of an amino acid naphthylamidase, naphthylamides of methionine, lysine, arginine, and alanine being hydrolyzed most rapidly. The rate of hydrolysis of BANA was only 11% of that of methionine naphthylamide. Amino acid esters with a free alpha-amino group were also good substrates. The transformation of type II to type I at acidic pH was studied. During the transformation amino acids or peptides were formed and probably some inhibitor present in type II was destroyed proteolytically.", "contents": "Alpha-N-Benzoylarginine-2-naphthylamide hydrolase (cathepsin BI?) from rat skin. III. Substrate specificity, modifier characteristics, and transformation of the enzyme at acidic pH. Some properties of rat skin benzoylarginine-2-naphthylamide hydrolase types I (preparations I and AI) and II (preparations II and NII) were studied. Both types were activated by dithiothreitol and EDTA, but responded differently to 1 mM KCN, when benzoylarginine-2-naphthylamide (BANA) was used as a substrate: type I was inhibited, while type II was activated. When leucine-2-naphthylamide was used as a substrate, both types were activated by KCN. Thiol proteinase inhibiting substances, like heavy metals, iodoacetic acid, 4-chloromercuribenzoic acid, and tosyllysine chloromethylketone, inhibited the enzymes. Diisopropylfluorophosphate, phenylmethylsulfonyfluoride, 4-aminobenzamidine, and high-molecular-weight trypsin inhibitors were without effect. The substrate specificity of rat skin BANA hydrolase resembled that of an amino acid naphthylamidase, naphthylamides of methionine, lysine, arginine, and alanine being hydrolyzed most rapidly. The rate of hydrolysis of BANA was only 11% of that of methionine naphthylamide. Amino acid esters with a free alpha-amino group were also good substrates. The transformation of type II to type I at acidic pH was studied. During the transformation amino acids or peptides were formed and probably some inhibitor present in type II was destroyed proteolytically."}
{"id": "PMID:7912", "title": "Heterogeneity of hepatic tyrosine aminotransferase. Separation of the multiple forms from rat and frog liver by isoelectric focussing and hydroxylapatite column chromatography and their partial characterization.", "content": "L-Tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5; TAT) and other enzymes that transaminate tyrosine in rat liver cytosol have been separated into four fractions by isoelectric focussing. One of the forms is probably identical to mitochondrial L-aspartate:2-oxoglutarate aminotransferase (EC 2.6.1.1.; mASAT). The other three forms have pI's of 4.72, 4.98 and 5.30 and Km values of 1.3 and 0.3 mM for tyrosine and alpha-ketoglutarate. These heat stable forms have little or no ASAT activity. Rat liver TAT is also separated into three peaks by hydroxylapatite. Each fraction gives only one peak of activity when electrofocussed separately. In the frog, three groups of peaks of TAT activity have been separated by hydroxylapatite column chromatography. The first group is connected with ASAT activity. These peaks (pI's 6.35, 6.50 and 6.90) are heat stable and have a Km value for tyrosine of 4 mM. These fractions probably represent cytoplasmic ASAT (sASAT). The second group of peaks has at least two subforms (pI's 9.0 and 9.4, Km for tyrosine 15 mM). These forms probably represent mASAT. The third group consists of three forms that resemble the major forms of rat liver TAT. These results indicate that heterogeneity is common to many aminotransferases and independent of regulation by glucocorticoids.", "contents": "Heterogeneity of hepatic tyrosine aminotransferase. Separation of the multiple forms from rat and frog liver by isoelectric focussing and hydroxylapatite column chromatography and their partial characterization. L-Tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5; TAT) and other enzymes that transaminate tyrosine in rat liver cytosol have been separated into four fractions by isoelectric focussing. One of the forms is probably identical to mitochondrial L-aspartate:2-oxoglutarate aminotransferase (EC 2.6.1.1.; mASAT). The other three forms have pI's of 4.72, 4.98 and 5.30 and Km values of 1.3 and 0.3 mM for tyrosine and alpha-ketoglutarate. These heat stable forms have little or no ASAT activity. Rat liver TAT is also separated into three peaks by hydroxylapatite. Each fraction gives only one peak of activity when electrofocussed separately. In the frog, three groups of peaks of TAT activity have been separated by hydroxylapatite column chromatography. The first group is connected with ASAT activity. These peaks (pI's 6.35, 6.50 and 6.90) are heat stable and have a Km value for tyrosine of 4 mM. These fractions probably represent cytoplasmic ASAT (sASAT). The second group of peaks has at least two subforms (pI's 9.0 and 9.4, Km for tyrosine 15 mM). These forms probably represent mASAT. The third group consists of three forms that resemble the major forms of rat liver TAT. These results indicate that heterogeneity is common to many aminotransferases and independent of regulation by glucocorticoids."}
{"id": "PMID:7915", "title": "Immunoglobulins in maxillary sinus secretion.", "content": "The immunoglobin pattern was studied in maxillary sinus secretion of 17 patients with maxillary sinusitis. By single radial immunodiffusion, measurable amounts of IgM were found in the secretions of 15 patients, and of IgA and IgG in the secretion of all patients. In purulent sinus secretion, IgA levels were significantly lower than in serous secretion. Of the total content of IgA in sinus secretion, 30% (purulent secretion) and 43% (serous secretion) were calculated to be locally produced, on average. For IgG these figures were 15% (purulent secretion) and 18% (serous secretion), whereas IgM could not be estimated by the method used. It was also concluded that the maxillary sinus is a suitable organ for investigation of local immunity in regard to bacterial infections.", "contents": "Immunoglobulins in maxillary sinus secretion. The immunoglobin pattern was studied in maxillary sinus secretion of 17 patients with maxillary sinusitis. By single radial immunodiffusion, measurable amounts of IgM were found in the secretions of 15 patients, and of IgA and IgG in the secretion of all patients. In purulent sinus secretion, IgA levels were significantly lower than in serous secretion. Of the total content of IgA in sinus secretion, 30% (purulent secretion) and 43% (serous secretion) were calculated to be locally produced, on average. For IgG these figures were 15% (purulent secretion) and 18% (serous secretion), whereas IgM could not be estimated by the method used. It was also concluded that the maxillary sinus is a suitable organ for investigation of local immunity in regard to bacterial infections."}
{"id": "PMID:7918", "title": "The effect of prolonged vasopressin administration on the level and metabolism of catecholamines in the rat brain and kidneys.", "content": "Dopamine (DA) and noradrenaline (NA) levels and activities of the enzymes metabolizing catecholamines were determined in the rat brain and kidneys during prolonged (4 weeks) administration of lysine vasopressin (LVP) and 2 weeks after its withdrawal. DA level was elevated during the whole period of experiment. NA level increased mainly after LVP withdrawal. Dopa-decarboxylase activity was elevated in all the experimental animals. Tyrosine and dopamine-beta-hydroxylase activities increased at the final period of LVP administration and after its withdrawal. Activities of MAO and COMT were markedly increased only after 3 weeks of LVP administration.", "contents": "The effect of prolonged vasopressin administration on the level and metabolism of catecholamines in the rat brain and kidneys. Dopamine (DA) and noradrenaline (NA) levels and activities of the enzymes metabolizing catecholamines were determined in the rat brain and kidneys during prolonged (4 weeks) administration of lysine vasopressin (LVP) and 2 weeks after its withdrawal. DA level was elevated during the whole period of experiment. NA level increased mainly after LVP withdrawal. Dopa-decarboxylase activity was elevated in all the experimental animals. Tyrosine and dopamine-beta-hydroxylase activities increased at the final period of LVP administration and after its withdrawal. Activities of MAO and COMT were markedly increased only after 3 weeks of LVP administration."}
{"id": "PMID:7923", "title": "[Physical and mental fatigue of probable hyperuricemia origin].", "content": "A blood uric acid analysis has been effected on 193 Iranians of the intellectual group aged from 25 to 60, of which the normal average rate for 99 women and 94 men of a normal state are (47.5 +/- 2.73) and (53.62 +/- 2.73) respectively. After having controlled the uricemia of these subjects during a period of three years in the three states of healthiness, fatigue or physical strains and sickness, we have been able to note that during physical fatigue and intellectual strains the uricemia presents an augmentation notable as in the case of the sicknesses. Taking into consideration the hyperuricemia resulting from fatigue and strains, it may be noteworthy to be taken into consideration by the clinical laboratories and the physicians as well.", "contents": "[Physical and mental fatigue of probable hyperuricemia origin]. A blood uric acid analysis has been effected on 193 Iranians of the intellectual group aged from 25 to 60, of which the normal average rate for 99 women and 94 men of a normal state are (47.5 +/- 2.73) and (53.62 +/- 2.73) respectively. After having controlled the uricemia of these subjects during a period of three years in the three states of healthiness, fatigue or physical strains and sickness, we have been able to note that during physical fatigue and intellectual strains the uricemia presents an augmentation notable as in the case of the sicknesses. Taking into consideration the hyperuricemia resulting from fatigue and strains, it may be noteworthy to be taken into consideration by the clinical laboratories and the physicians as well."}
{"id": "PMID:7919", "title": "The effect of adrenergic blocking and stimulating agents on arginine vasotocin release in birds.", "content": "The effect of adrenergic blocking and stimulating agents on arginine vasotocin (AVT) release from the neurohpophysis following osmotic stimuli was studied in hens. It was found that alpha - adrenergic blocking drug - regitine inhibits the release of AVT after the intravenous injection of hypertonic solution of NaCl. The alpha - adrenergic stimulating drug - vasoxine as well as beta - adrenergic blocking drug - propranolol and beta - stimulating drug isoprenalinsulphate had no effect on the release of AVT.", "contents": "The effect of adrenergic blocking and stimulating agents on arginine vasotocin release in birds. The effect of adrenergic blocking and stimulating agents on arginine vasotocin (AVT) release from the neurohpophysis following osmotic stimuli was studied in hens. It was found that alpha - adrenergic blocking drug - regitine inhibits the release of AVT after the intravenous injection of hypertonic solution of NaCl. The alpha - adrenergic stimulating drug - vasoxine as well as beta - adrenergic blocking drug - propranolol and beta - stimulating drug isoprenalinsulphate had no effect on the release of AVT."}
{"id": "PMID:7920", "title": "Studies on the activity of cholinesterase included on silica gel.", "content": "Cholinesterase was immobilized in silica gel. The activity of the bound enzyme was determined by comparing the concentrations of hydrogen ions in the solution entering and leaving the reactor, filled with a suspension of the insoluble enzyme in Sephadex.", "contents": "Studies on the activity of cholinesterase included on silica gel. Cholinesterase was immobilized in silica gel. The activity of the bound enzyme was determined by comparing the concentrations of hydrogen ions in the solution entering and leaving the reactor, filled with a suspension of the insoluble enzyme in Sephadex."}
{"id": "PMID:7926", "title": "Amino acid transport in isolated neurons and glia.", "content": "Our efforts have been directed towards characterizing amino acid uptake, metabolism and release in bulk-isolated glia and neuronal perikarya studied in parallel with nerve-endings, especially as it concerns the transmitter amino acids and the participation of glia in the clearing of the synpatic space during impulse conduction. A possible neuromodulator role for the glia at the synapse is also suggested by K+-stimulated release. Our most definitive conclusions have been based so far on studies with GABA, although we are also beginning to accumulate data for glutamate related to glutamate-glutamine compartmentation. Glia preferentially accumulate potassium and amino acids compared to neuronal perikarya, have higher Na+/K+-ATPase activity, possess high-affinity, sodium-dependent uptake systems for GABA and glutamate similar to the ones in synaptosomes, and release amino acid in response to a potassium pulse by a calcium-independent process. Low neuronal uptake could be due to loss of dendrites. Unidirectional GABA-flux from the synaptosomal to glial compartment is supported by high GAD in nerve endings compared to high GABA-T in glia. Glutamine may be a transmitter glutamate-precursor in nerve-endings since glutaminase activity is high in nerve-endings, but low in glia where glutamine is presumably made. Glutamine uptake in both glia and synaptosomes obeys low-affinity kinetics in contrast to glutamate, consistent with the inability of glutamine to excite the neuronal membrane. The studies with GABA, which are considerably more extensive, are supported by related work using glia in tissue-culture and autoradiography. There appears to be a suggested difference in the behavior of amines which were poorly taken up by the glial system. Glia, synaptosomes and neuronal perikarya, in general behaved similarly with respect to requirements for uptake and release, except in the case of Ca++, which exerted opposite effects on glial and synaptosomal uptake of GABA. We believe that work along these lines tends to firmly establish a direct role for glial cells as modulators of neuronal excitability and represents a convergence between transmitter amino acid neuropharmacology and cellular biochemistry. This not only deepens and enlarges the vocabulary of synaptic biochemistry but also undoubtedly will have major clinical applications in the fields of epilepsy and behavior.", "contents": "Amino acid transport in isolated neurons and glia. Our efforts have been directed towards characterizing amino acid uptake, metabolism and release in bulk-isolated glia and neuronal perikarya studied in parallel with nerve-endings, especially as it concerns the transmitter amino acids and the participation of glia in the clearing of the synpatic space during impulse conduction. A possible neuromodulator role for the glia at the synapse is also suggested by K+-stimulated release. Our most definitive conclusions have been based so far on studies with GABA, although we are also beginning to accumulate data for glutamate related to glutamate-glutamine compartmentation. Glia preferentially accumulate potassium and amino acids compared to neuronal perikarya, have higher Na+/K+-ATPase activity, possess high-affinity, sodium-dependent uptake systems for GABA and glutamate similar to the ones in synaptosomes, and release amino acid in response to a potassium pulse by a calcium-independent process. Low neuronal uptake could be due to loss of dendrites. Unidirectional GABA-flux from the synaptosomal to glial compartment is supported by high GAD in nerve endings compared to high GABA-T in glia. Glutamine may be a transmitter glutamate-precursor in nerve-endings since glutaminase activity is high in nerve-endings, but low in glia where glutamine is presumably made. Glutamine uptake in both glia and synaptosomes obeys low-affinity kinetics in contrast to glutamate, consistent with the inability of glutamine to excite the neuronal membrane. The studies with GABA, which are considerably more extensive, are supported by related work using glia in tissue-culture and autoradiography. There appears to be a suggested difference in the behavior of amines which were poorly taken up by the glial system. Glia, synaptosomes and neuronal perikarya, in general behaved similarly with respect to requirements for uptake and release, except in the case of Ca++, which exerted opposite effects on glial and synaptosomal uptake of GABA. We believe that work along these lines tends to firmly establish a direct role for glial cells as modulators of neuronal excitability and represents a convergence between transmitter amino acid neuropharmacology and cellular biochemistry. This not only deepens and enlarges the vocabulary of synaptic biochemistry but also undoubtedly will have major clinical applications in the fields of epilepsy and behavior."}
{"id": "PMID:7933", "title": "Mediation of macrophage effector function by lymphokine.", "content": "The progressive effect of lymphokine contact on macrophages in vitro has been studied using various quantitative cytochemical techniques. Changes in the physiology of the macrophages have been seen rapidly after lymphokine contact. These appear to correlate with the functional effect of inhibition of migration. After more prolonged contact with lymphokine however, the macrophages exhibit different changes to their physiology and reach a state of enhanced cytochemical activity which has been termed 'activation'. By comparing the rapid effect of lymphokine to the changes seen after prolonged contact it is suggested that one can rationalize the apparent paradoxical effects of these soluble mediators which appear initially to 'turn off' the macrophage and subsequently 'activate' the same cell. In doing so an hypothesis is put forward as to how this mediator might work in vivo.", "contents": "Mediation of macrophage effector function by lymphokine. The progressive effect of lymphokine contact on macrophages in vitro has been studied using various quantitative cytochemical techniques. Changes in the physiology of the macrophages have been seen rapidly after lymphokine contact. These appear to correlate with the functional effect of inhibition of migration. After more prolonged contact with lymphokine however, the macrophages exhibit different changes to their physiology and reach a state of enhanced cytochemical activity which has been termed 'activation'. By comparing the rapid effect of lymphokine to the changes seen after prolonged contact it is suggested that one can rationalize the apparent paradoxical effects of these soluble mediators which appear initially to 'turn off' the macrophage and subsequently 'activate' the same cell. In doing so an hypothesis is put forward as to how this mediator might work in vivo."}
{"id": "PMID:7934", "title": "Inhibition of prostaglandin synthesis in vivo by nonsteroid anti-inflammatory drugs: evidence for the importance of pharmacokinetics.", "content": "A variety of acidic and non-acidic compounds are potent inhibitors of prostaglandin (PG) synthesis in vitro. However, only a few, namely the acidic nonsteroid anti-inflammatory drugs (NSAID) are useful anti-inflammatory analgesics in the clinic. Since inhibition of PG-synthesis is believed to be the main target of NSAID in inflammation this superiority of acidic compounds remains unexplained. We have considered that one explanation could be that only acidic NSAID appear in high concentrations in inflamed tissue to inhibit PG-synthesis sufficiently. To test this hypothesis the following experiments were carried out: (A) PG-synthesis and its inhibition by acidic and non-acidic NSAID was measured in vivo at the site of inflammation. It was found that in therapeutic doses only acidic NSAID were capable to reduce PG-synthesis significantly. (B) Measurement of drug concentration in inflamed tissue showed that only acidic NSAID were found in significantly higher concentrations in inflamed than in control tissue. From these observations it is concluded that a specific pharmacokinetic behaviour of acidic NSAID leading to high concentrations in inflamed tissue is a decisive aspect of their anti-inflammatory action.", "contents": "Inhibition of prostaglandin synthesis in vivo by nonsteroid anti-inflammatory drugs: evidence for the importance of pharmacokinetics. A variety of acidic and non-acidic compounds are potent inhibitors of prostaglandin (PG) synthesis in vitro. However, only a few, namely the acidic nonsteroid anti-inflammatory drugs (NSAID) are useful anti-inflammatory analgesics in the clinic. Since inhibition of PG-synthesis is believed to be the main target of NSAID in inflammation this superiority of acidic compounds remains unexplained. We have considered that one explanation could be that only acidic NSAID appear in high concentrations in inflamed tissue to inhibit PG-synthesis sufficiently. To test this hypothesis the following experiments were carried out: (A) PG-synthesis and its inhibition by acidic and non-acidic NSAID was measured in vivo at the site of inflammation. It was found that in therapeutic doses only acidic NSAID were capable to reduce PG-synthesis significantly. (B) Measurement of drug concentration in inflamed tissue showed that only acidic NSAID were found in significantly higher concentrations in inflamed than in control tissue. From these observations it is concluded that a specific pharmacokinetic behaviour of acidic NSAID leading to high concentrations in inflamed tissue is a decisive aspect of their anti-inflammatory action."}
{"id": "PMID:7935", "title": "Electrophoretic separation and characterization of subunits released from influenza virus by detergents.", "content": "Subunits released from influenza A/Singapore/1/57 (H2N2) virus by either Triton-X-100 (T-X-100); or sodium lauryl sarcosinate (SLS) or ether were separated by electrophoresis in agarose suspension into a rapidly migrating fraction (I) and a slowly migrating fraction (II). Fraction I obtained after T-X-100 treatment contained the viral ribonucleoprotein (RNP) in a form indistinguishable from the obtained after ether treatment. SLS treatment of the virus resulted in a rapidly migrating fraction containing only the protein part of the viral RNP. Fraction II obtained after T-X-100 or SLS treatment contained both haemagglutinin (HA) and neuraminidase (NA), mostly dissociated from each other, in contrast to fraction II obtained after ether treatment which contained mixed aggregates of HA and NA. The yields of electrophoretically isolated RNP and HA-NA were essentially the same irrespective of whether T-X-100 or ether was used for virus disruption. Treatment of virus by T-X-100 and subsequent removal of the latter resulted in a 10-20-fold increase of the HA activity. After sodium dodecyl sulphate (SDS) treatment of the virus, the NA activity was found in a heterogeneous fraction with surprisingly high migration rate towards the anode, indicating that NA remained active despite its extensive SDS binding.", "contents": "Electrophoretic separation and characterization of subunits released from influenza virus by detergents. Subunits released from influenza A/Singapore/1/57 (H2N2) virus by either Triton-X-100 (T-X-100); or sodium lauryl sarcosinate (SLS) or ether were separated by electrophoresis in agarose suspension into a rapidly migrating fraction (I) and a slowly migrating fraction (II). Fraction I obtained after T-X-100 treatment contained the viral ribonucleoprotein (RNP) in a form indistinguishable from the obtained after ether treatment. SLS treatment of the virus resulted in a rapidly migrating fraction containing only the protein part of the viral RNP. Fraction II obtained after T-X-100 or SLS treatment contained both haemagglutinin (HA) and neuraminidase (NA), mostly dissociated from each other, in contrast to fraction II obtained after ether treatment which contained mixed aggregates of HA and NA. The yields of electrophoretically isolated RNP and HA-NA were essentially the same irrespective of whether T-X-100 or ether was used for virus disruption. Treatment of virus by T-X-100 and subsequent removal of the latter resulted in a 10-20-fold increase of the HA activity. After sodium dodecyl sulphate (SDS) treatment of the virus, the NA activity was found in a heterogeneous fraction with surprisingly high migration rate towards the anode, indicating that NA remained active despite its extensive SDS binding."}
{"id": "PMID:7936", "title": "The effect of combination of different inducers on the refractory state in interferon production.", "content": "A second injection of 100 mug poly (rI) poly (rC) per mouse at 6 and 24 hours after the first injection stimulated additional peaks of interferon production. The dynamics of the process of accumulation and disappearance of interferon was similar to that after a single injection of poly (rI). poly (rC). Injection of the above dose 12 hours after the first injection induced no interferon production as it apparently coincided with the refractory state in interferon production. After pretreatment of poly (rI) poly (rC) with DEAE-dextran, the refractory phase occurred in 6 hours. Inoculation of Venezuelan equine encephalomyelitis virus as a second interferon inducer resulted in a repeated stimulation of interferon production both in animals and in tissue culture; however, interferon titres in this case were low. The use of an inactivated virus as a second interferon inducer stimulated interferon production to higher titres (5120 IU/ml) than a single injection of DEAE-dextran-treated poly (rI). poly (rC). It is possible that a combined use of poly (rI). poly (rC) and noninfectious virus as a second interferon inducer eliminates the development of the refractory state.", "contents": "The effect of combination of different inducers on the refractory state in interferon production. A second injection of 100 mug poly (rI) poly (rC) per mouse at 6 and 24 hours after the first injection stimulated additional peaks of interferon production. The dynamics of the process of accumulation and disappearance of interferon was similar to that after a single injection of poly (rI). poly (rC). Injection of the above dose 12 hours after the first injection induced no interferon production as it apparently coincided with the refractory state in interferon production. After pretreatment of poly (rI) poly (rC) with DEAE-dextran, the refractory phase occurred in 6 hours. Inoculation of Venezuelan equine encephalomyelitis virus as a second interferon inducer resulted in a repeated stimulation of interferon production both in animals and in tissue culture; however, interferon titres in this case were low. The use of an inactivated virus as a second interferon inducer stimulated interferon production to higher titres (5120 IU/ml) than a single injection of DEAE-dextran-treated poly (rI). poly (rC). It is possible that a combined use of poly (rI). poly (rC) and noninfectious virus as a second interferon inducer eliminates the development of the refractory state."}
{"id": "PMID:7937", "title": "The dynamics of development of cell resistance to viruses induced by synthetic polynucleotides.", "content": "The dynamics of interaction of complexes of synthetic polynucleotides (polyinosinic and polycitidylic acid--poly (rI)-poly (rC), and polyguanylic and polycytidylic acid--poly (rG)-poly (rC)) with cells as well as the dynamics of interferon accumulation and development of antiviral effect against some RNA viruses were studied in primary chick embryo cell (CEC) cultures. Four phases were observed in the development of the antiviral effect of synthetic polynucleotides: adsorption, increase, marked antiviral effect and waning. The duration and extent of the antiviral effect depended upon the activity and the dose of the preparation and less so upon virus type. At the same time, the dynamics of the development of the antiviral effect in early stages differed significantly depending on the virus model.", "contents": "The dynamics of development of cell resistance to viruses induced by synthetic polynucleotides. The dynamics of interaction of complexes of synthetic polynucleotides (polyinosinic and polycitidylic acid--poly (rI)-poly (rC), and polyguanylic and polycytidylic acid--poly (rG)-poly (rC)) with cells as well as the dynamics of interferon accumulation and development of antiviral effect against some RNA viruses were studied in primary chick embryo cell (CEC) cultures. Four phases were observed in the development of the antiviral effect of synthetic polynucleotides: adsorption, increase, marked antiviral effect and waning. The duration and extent of the antiviral effect depended upon the activity and the dose of the preparation and less so upon virus type. At the same time, the dynamics of the development of the antiviral effect in early stages differed significantly depending on the virus model."}
{"id": "PMID:7938", "title": "Biochemical classification of herpes simplex virus types 1 and 2, and of intermediate strains on the basis of different susceptibilities of thymidine kinase to thymidine analogues.", "content": "Herpes simplex virus (HSV) type 1 can be differentiated from HSV type 2 on the basis of the sensitivity to 2'-deoxythymidine-5'-monophosphate of thymidine kinase induced in primary rabbit kidney cells. Whereas thymidine kinase induced by five strains of HSV type 1 (TK 1) is stimulated by suitable concentrations of 2'-deoxythymidine-5'-monophosphate, thymidine kinase induced by eight strains of HSV type 2 (TK 2) is inhibited. On the other hand, TK 2 is strongly inhibited by 2'-deoxythymidine-5'-triphosphate and by 2-bromo-2'-deoxyuridine-5'-triphosphate. The investigation of TK induced by six freshly isolated strains of HSV cross-reacting in neutralisation tests revealed two strains which induced TK 1 and two strains which induced TK 2. Two other strains induced thymidine kinase, the activity of which under the influence of these thymidine analogues was between that of TK 1 and TK 2. The properties of thymidine kinase remained constant after cloning the virus and thus is a genetically fixed trait due to recombination which could well occur in vivo.", "contents": "Biochemical classification of herpes simplex virus types 1 and 2, and of intermediate strains on the basis of different susceptibilities of thymidine kinase to thymidine analogues. Herpes simplex virus (HSV) type 1 can be differentiated from HSV type 2 on the basis of the sensitivity to 2'-deoxythymidine-5'-monophosphate of thymidine kinase induced in primary rabbit kidney cells. Whereas thymidine kinase induced by five strains of HSV type 1 (TK 1) is stimulated by suitable concentrations of 2'-deoxythymidine-5'-monophosphate, thymidine kinase induced by eight strains of HSV type 2 (TK 2) is inhibited. On the other hand, TK 2 is strongly inhibited by 2'-deoxythymidine-5'-triphosphate and by 2-bromo-2'-deoxyuridine-5'-triphosphate. The investigation of TK induced by six freshly isolated strains of HSV cross-reacting in neutralisation tests revealed two strains which induced TK 1 and two strains which induced TK 2. Two other strains induced thymidine kinase, the activity of which under the influence of these thymidine analogues was between that of TK 1 and TK 2. The properties of thymidine kinase remained constant after cloning the virus and thus is a genetically fixed trait due to recombination which could well occur in vivo."}
{"id": "PMID:7939", "title": "Persistent infection of BHK cells with herpes simplex virus types 1 and 2 in the absence of specific anti-herpetic antibody.", "content": "Persistent infection of BHK-21 cells with 5 strains of herpes simplex virus (HSV) type 1 and a 1 strain of HSV type 2 is described. Acute infection only was obtained with two strains of type 1 and one strain of type 2. Persistent infection could not be established in HeLa and rabbit lung cells. Persistent infection of BHK cells proceeded in the absence of specific antibody. Persistently infected cells were more resistant to superinfection with homologous or heterologous HSV as compared to infection of normal BHK cells. No interferon activity was demonstrated in persistently infected cell cultures. The results of virus titration were in accordance with the demonstration of fluorescent antigen of HSV.", "contents": "Persistent infection of BHK cells with herpes simplex virus types 1 and 2 in the absence of specific anti-herpetic antibody. Persistent infection of BHK-21 cells with 5 strains of herpes simplex virus (HSV) type 1 and a 1 strain of HSV type 2 is described. Acute infection only was obtained with two strains of type 1 and one strain of type 2. Persistent infection could not be established in HeLa and rabbit lung cells. Persistent infection of BHK cells proceeded in the absence of specific antibody. Persistently infected cells were more resistant to superinfection with homologous or heterologous HSV as compared to infection of normal BHK cells. No interferon activity was demonstrated in persistently infected cell cultures. The results of virus titration were in accordance with the demonstration of fluorescent antigen of HSV."}
{"id": "PMID:7940", "title": "Reactions of immune sera against the nucleocapsid, envelope and whole herpes simplex virus type 1.", "content": "Antibodies against (a) naked particles, (b) virus envelope, and (c) whole herpes simplex virus (HSV) type 1 were investigated. Immune rabbit serum against naked particles (and formalized naked particles) contained virus neutralizing (VN) antibody in a low titre as compared to the titre of complement-fixing (CF) antibody. Immune rabbit serum against the viral envelope had similar titres of VN and CF antibodies. In gel double diffusion precipitation tests, whole HSV gave two precipitation zones with antibodies against naked particles two zones with antibodies against the virus envelope, several zones with antibodies against whole virus and two marked zones against human convalescent serum. Viral nucleocapsid reacted with two zones with antibodies against the nucleocapsid and a faint zone with antibodies against the virus envelope. The envelopes gave two zones with antibodies against whole virus and a faint zone with antibodies against naked particles. Human convalescent serum gave a single precipitation zone with viral nucleocapsid and two zones with virus envelope and whole virus.", "contents": "Reactions of immune sera against the nucleocapsid, envelope and whole herpes simplex virus type 1. Antibodies against (a) naked particles, (b) virus envelope, and (c) whole herpes simplex virus (HSV) type 1 were investigated. Immune rabbit serum against naked particles (and formalized naked particles) contained virus neutralizing (VN) antibody in a low titre as compared to the titre of complement-fixing (CF) antibody. Immune rabbit serum against the viral envelope had similar titres of VN and CF antibodies. In gel double diffusion precipitation tests, whole HSV gave two precipitation zones with antibodies against naked particles two zones with antibodies against the virus envelope, several zones with antibodies against whole virus and two marked zones against human convalescent serum. Viral nucleocapsid reacted with two zones with antibodies against the nucleocapsid and a faint zone with antibodies against the virus envelope. The envelopes gave two zones with antibodies against whole virus and a faint zone with antibodies against naked particles. Human convalescent serum gave a single precipitation zone with viral nucleocapsid and two zones with virus envelope and whole virus."}
{"id": "PMID:7941", "title": "Gel chromatography of serum from mice infected with a virus elevating L-lactate: NAD oxidoreductase activity--an attempt to separate viral and enzymatic activities.", "content": "Gel chromatography on Spheron P-500 of mouse serum yielded fractions elevating lactate dehydrogenase activity. The order of elution was viral activity, proteins and lactate dehydrogenase activity. Viral contamination occurred also in certain fractions subjected to repeated gel chromatography in which no proteins were detectable.", "contents": "Gel chromatography of serum from mice infected with a virus elevating L-lactate: NAD oxidoreductase activity--an attempt to separate viral and enzymatic activities. Gel chromatography on Spheron P-500 of mouse serum yielded fractions elevating lactate dehydrogenase activity. The order of elution was viral activity, proteins and lactate dehydrogenase activity. Viral contamination occurred also in certain fractions subjected to repeated gel chromatography in which no proteins were detectable."}
{"id": "PMID:7942", "title": "Further experiments on the action of antithymocyte serum in experimental Jun\u00edn virus infection.", "content": "Rabbit anti-mouse thymocyte serum (ATS) administrated as late as 7 days after infection suppressed host cell-mediated responsiveness to intracerebrally injected Jun\u00edn virus, thereby diminishing the morbility and mortality of this infection. It did not affect either the humoral antibody response or the virus titer in brain. This findings suggest that: a) in mouse brain cells, Jun\u00edn virus infection is basically non-cytopathic: b) cell-mediated immunity is responsible for morbility and mortality and does not clear up virus from brain as in other viral encephalitides; and c) ATS may be of therapeutic interest by suppressing or diminishing the cell-mediated response to Jun\u00edn virus.", "contents": "Further experiments on the action of antithymocyte serum in experimental Jun\u00edn virus infection. Rabbit anti-mouse thymocyte serum (ATS) administrated as late as 7 days after infection suppressed host cell-mediated responsiveness to intracerebrally injected Jun\u00edn virus, thereby diminishing the morbility and mortality of this infection. It did not affect either the humoral antibody response or the virus titer in brain. This findings suggest that: a) in mouse brain cells, Jun\u00edn virus infection is basically non-cytopathic: b) cell-mediated immunity is responsible for morbility and mortality and does not clear up virus from brain as in other viral encephalitides; and c) ATS may be of therapeutic interest by suppressing or diminishing the cell-mediated response to Jun\u00edn virus."}
{"id": "PMID:7943", "title": "The value of complement fixation and haemagglutination inhibition tests in the diagnosis of influenza A.", "content": "Antibody response of 133 influenza A patients from three outbreaks since 1972-73 was analyzed by complement fixation (CF) and haemagglutination inhibition (HI) methods. During the first outbreak, a significant response was more often measured by CF than by HI. During the last outbreak HI appeared more useful than CF for routine serological diagnosis; 23% of cases verified by HI were missed by CF. The poor response of CF antibodies was associated with the high level of pre-infection antibodies.", "contents": "The value of complement fixation and haemagglutination inhibition tests in the diagnosis of influenza A. Antibody response of 133 influenza A patients from three outbreaks since 1972-73 was analyzed by complement fixation (CF) and haemagglutination inhibition (HI) methods. During the first outbreak, a significant response was more often measured by CF than by HI. During the last outbreak HI appeared more useful than CF for routine serological diagnosis; 23% of cases verified by HI were missed by CF. The poor response of CF antibodies was associated with the high level of pre-infection antibodies."}
{"id": "PMID:7944", "title": "Susceptibility of various cell lines to virulent and attenuated strains of pseudorabies virus.", "content": "Various cell lines were infected with virulent and attenuated strains of pseudorabies virus (PRV). According to the type of the cytopathic effect (CPE), the cells could be divided into 3 groups: cells in which all strains formed syncytia; cells in which all strains caused rounding of cells; and cells in which virulent strains caused syncytium formation while attenuated ones rounding of cells. Neither the form (fibroblastoid or epithelial) nor the origin of cells influenced the type of the CPE. L cells and some cell lines derived from human tissue proved to be less sensitive to PRV than other cells. In certain human cells (e.g. HeLa and D6) virulent PRV strains propagated better than attenuated ones.", "contents": "Susceptibility of various cell lines to virulent and attenuated strains of pseudorabies virus. Various cell lines were infected with virulent and attenuated strains of pseudorabies virus (PRV). According to the type of the cytopathic effect (CPE), the cells could be divided into 3 groups: cells in which all strains formed syncytia; cells in which all strains caused rounding of cells; and cells in which virulent strains caused syncytium formation while attenuated ones rounding of cells. Neither the form (fibroblastoid or epithelial) nor the origin of cells influenced the type of the CPE. L cells and some cell lines derived from human tissue proved to be less sensitive to PRV than other cells. In certain human cells (e.g. HeLa and D6) virulent PRV strains propagated better than attenuated ones."}
{"id": "PMID:7946", "title": "Incidence of arbovirus antibodies in bovine, ovine and human sera collected in Eastern Sicily.", "content": "The incidence of antibodies against 9 arboviruses in ovine, bovine and human sera collected in Eastern Sicily was studied. A high incidence of antibodies was found especially against Bhanja virus in all sera and against Sandfly fever Sicilian in ovine sera only. The incidence was higher than that reported in 1971 for the western part of Sicily. These findings suggest an increase in the circulation of arboviruses in this area; the causes are briefly discussed.", "contents": "Incidence of arbovirus antibodies in bovine, ovine and human sera collected in Eastern Sicily. The incidence of antibodies against 9 arboviruses in ovine, bovine and human sera collected in Eastern Sicily was studied. A high incidence of antibodies was found especially against Bhanja virus in all sera and against Sandfly fever Sicilian in ovine sera only. The incidence was higher than that reported in 1971 for the western part of Sicily. These findings suggest an increase in the circulation of arboviruses in this area; the causes are briefly discussed."}
{"id": "PMID:7947", "title": "\"White-wild\" (variola-like) poxvirus strains from rodents in Equatorial Africa.", "content": "Strains of variola-like virus were isolated from rodents, namely 1 each from Mastomys coucha (fam. Muridae) and Helioscorus rufobrachium (fam. Sciuridae) in the Bumba zone of the Equatorial province of the Zaire Republic. Attempts to isolate the virus from 48 monkeys were negative. Neutralizing antibodies were found in 1 of 7 monkey (Cercopithecus ascanius schmidti) sera examined as well as in the serum of H. rufobrachium from which the virus was isolated.", "contents": "\"White-wild\" (variola-like) poxvirus strains from rodents in Equatorial Africa. Strains of variola-like virus were isolated from rodents, namely 1 each from Mastomys coucha (fam. Muridae) and Helioscorus rufobrachium (fam. Sciuridae) in the Bumba zone of the Equatorial province of the Zaire Republic. Attempts to isolate the virus from 48 monkeys were negative. Neutralizing antibodies were found in 1 of 7 monkey (Cercopithecus ascanius schmidti) sera examined as well as in the serum of H. rufobrachium from which the virus was isolated."}
{"id": "PMID:7948", "title": "Variable response of normal and transformed mouse cells to interferon inducers.", "content": "Balb/3T3 mouse cells, normal and SV40-transformed, produced interferon when induced with Newcastle disease and influenza viruses; transformed cells failed to respond to double-stranded RNA inducers.", "contents": "Variable response of normal and transformed mouse cells to interferon inducers. Balb/3T3 mouse cells, normal and SV40-transformed, produced interferon when induced with Newcastle disease and influenza viruses; transformed cells failed to respond to double-stranded RNA inducers."}
{"id": "PMID:7949", "title": "Consumption of complement in chelated and nonchelated guinea pig serum after challenge with some viral and nonviral interferon inducers.", "content": "The consumption of complement observed during the induction of interferon by various inducers may proceed via the alternate pathway. The alternate pathway requires the presence of Mg ions in the medium while Ca ions may be absent.", "contents": "Consumption of complement in chelated and nonchelated guinea pig serum after challenge with some viral and nonviral interferon inducers. The consumption of complement observed during the induction of interferon by various inducers may proceed via the alternate pathway. The alternate pathway requires the presence of Mg ions in the medium while Ca ions may be absent."}
{"id": "PMID:7951", "title": "The dynamics of production and the sensitivity to cycloheximide and actinomycin D of interferon-inducing and interferon messenger RNA.", "content": "In the process of virus-induced interferon production, two kinds of RNA appear in the cells. One of them induces production by the recipient cells of interferon with the species-specificity of the latter cells (interferon-inducing RNA), and the other is translated by the recipient cells pre-treated with actinomycin D into interferon with the species-specificity of the donor cells of RNA (interferon mRNA). The interferon-inducing RNA appears 20-30 minutes after virus induction and shows maximal activity after 1 hour. Its formation is not influenced by cycloheximide or actinomycin D. This RNA is assumed to be a transcriptive intermediate form of viral RNA. Interferon mRNA appears in the cells 1 hour after virus induction and shows maximal activity after 6-8 hours. Its synthesis is inhibited by cycloheximide and actinomycin D.", "contents": "The dynamics of production and the sensitivity to cycloheximide and actinomycin D of interferon-inducing and interferon messenger RNA. In the process of virus-induced interferon production, two kinds of RNA appear in the cells. One of them induces production by the recipient cells of interferon with the species-specificity of the latter cells (interferon-inducing RNA), and the other is translated by the recipient cells pre-treated with actinomycin D into interferon with the species-specificity of the donor cells of RNA (interferon mRNA). The interferon-inducing RNA appears 20-30 minutes after virus induction and shows maximal activity after 1 hour. Its formation is not influenced by cycloheximide or actinomycin D. This RNA is assumed to be a transcriptive intermediate form of viral RNA. Interferon mRNA appears in the cells 1 hour after virus induction and shows maximal activity after 6-8 hours. Its synthesis is inhibited by cycloheximide and actinomycin D."}
{"id": "PMID:7952", "title": "Efficacy of cardioselective beta adrenergic blockade with intravenously administered tolamolol in the treatment of cardiac arrhythmias.", "content": "The efficacy of tolamolol, a cardioselective beta adrenergic blocking agent, was evaluated in the treatment of cardiac arrhythmias in 27 patients. Nineteen patients had supraventricular arrhythmias and eight had ventricular arrhythmias. Evaluation was by doulbe-blind randomized trial in 23 patients. Tolamolol was effective in reducing ventricular rate in 17 (85 percent) of 19 patients with supraventricular arrhythmias and resulted in conversion to sinus rhythm in 2 of the 17. The mean ventricular rate in 17 patients decreased from 135 to 102/min 10 minutes after initiation of administration of tolamolol and gradually decreased further to 93/min after 60 minutes. Reduction in ventricular rate was sustained for 2 hours of monitoring undergone by all patients and for 4 and 6 hours monitoring in two subgroups. Among the eight patients with ventricular ectopic beats, tolamolol reduced their frequency in four patients and had no effect in four. Six patients had chronic obstructive pulmonary disease and experienced no adverse clinical effects on respiratory function in association with administration to tolamolol. Untoward effects occurred in 10 patients, including hypotension in 3, 1 of whom required vasopressor therapy. Other side effects were sedation, nausea, dyspnea and warmth in the chest, all of which were mild and transient, requiring no treatment. Cardioselective beta adrenergic blockade with tolamolol was highly effective in controlling ventricular rate in supraventricular arrhythmias and reduced the frequency of ventricular ectopic beats in half of the small group of patients with this arrhythmia. It is particularly applicable in patients with obstructive pulmonary disease in whom cardiac beta adrenergic blockade is indicated. Hypotension is an important potential side effect.", "contents": "Efficacy of cardioselective beta adrenergic blockade with intravenously administered tolamolol in the treatment of cardiac arrhythmias. The efficacy of tolamolol, a cardioselective beta adrenergic blocking agent, was evaluated in the treatment of cardiac arrhythmias in 27 patients. Nineteen patients had supraventricular arrhythmias and eight had ventricular arrhythmias. Evaluation was by doulbe-blind randomized trial in 23 patients. Tolamolol was effective in reducing ventricular rate in 17 (85 percent) of 19 patients with supraventricular arrhythmias and resulted in conversion to sinus rhythm in 2 of the 17. The mean ventricular rate in 17 patients decreased from 135 to 102/min 10 minutes after initiation of administration of tolamolol and gradually decreased further to 93/min after 60 minutes. Reduction in ventricular rate was sustained for 2 hours of monitoring undergone by all patients and for 4 and 6 hours monitoring in two subgroups. Among the eight patients with ventricular ectopic beats, tolamolol reduced their frequency in four patients and had no effect in four. Six patients had chronic obstructive pulmonary disease and experienced no adverse clinical effects on respiratory function in association with administration to tolamolol. Untoward effects occurred in 10 patients, including hypotension in 3, 1 of whom required vasopressor therapy. Other side effects were sedation, nausea, dyspnea and warmth in the chest, all of which were mild and transient, requiring no treatment. Cardioselective beta adrenergic blockade with tolamolol was highly effective in controlling ventricular rate in supraventricular arrhythmias and reduced the frequency of ventricular ectopic beats in half of the small group of patients with this arrhythmia. It is particularly applicable in patients with obstructive pulmonary disease in whom cardiac beta adrenergic blockade is indicated. Hypotension is an important potential side effect."}
{"id": "PMID:7953", "title": "Ultrastructural changes of the canine gastric mucosa after topical application of graded concentrations of ethanol.", "content": "Changes in the fine structure of the gastric mucosa following exposure to graded concentrations of ethanol were studied in dogs. 300 ml of 12.5, 20, and 40%, vol/vol, were instilled intragastrically for 30 min. Mucosa from the midbody and midantrum along the greater curvature was examined by light and electron microscopy. Ethanol produced a gradation of changes in the surface epithelial cells and in the lamina propria without affecting the parietal cells and chief cells. 12.5% ethanol produced widened and irregular intercellular spaces while 20 and 40% disrupted the apical cell membrane with concomitant exudation of mucin into the gastric lumen. These changes were more severe after 40% ethanol. The tight junction between cells remained intact following exposure to the lower concentrations of ethanol, but focal separation of cell junctions was observed in severely damaged areas. Quantitation of protein, sodium, and potassium concentrations in the gastric contents revealed marked increases following exposure to ethanol which correlated with the concentration. These studies provide additional morphological data on the relationship between structural changes and functional abnormalities induced by agents which break the gastric mucosal barrier.", "contents": "Ultrastructural changes of the canine gastric mucosa after topical application of graded concentrations of ethanol. Changes in the fine structure of the gastric mucosa following exposure to graded concentrations of ethanol were studied in dogs. 300 ml of 12.5, 20, and 40%, vol/vol, were instilled intragastrically for 30 min. Mucosa from the midbody and midantrum along the greater curvature was examined by light and electron microscopy. Ethanol produced a gradation of changes in the surface epithelial cells and in the lamina propria without affecting the parietal cells and chief cells. 12.5% ethanol produced widened and irregular intercellular spaces while 20 and 40% disrupted the apical cell membrane with concomitant exudation of mucin into the gastric lumen. These changes were more severe after 40% ethanol. The tight junction between cells remained intact following exposure to the lower concentrations of ethanol, but focal separation of cell junctions was observed in severely damaged areas. Quantitation of protein, sodium, and potassium concentrations in the gastric contents revealed marked increases following exposure to ethanol which correlated with the concentration. These studies provide additional morphological data on the relationship between structural changes and functional abnormalities induced by agents which break the gastric mucosal barrier."}
{"id": "PMID:7954", "title": "Some minimal effects of bile acid on canine gastric mucosa in Heidenhain pouches.", "content": "The gastric mucosa in four canine Heidenhain pouches was damaged with sodium taurocholate in a concentration which was just sufficient in each dog to produce consistent changes. Solutions were placed in the pouches and changes in the volume, concentrations, and fluxes of both hydrogen ion and sodium ion were measured before and during exposure to taurocholate. Changes which occurred with taurocholate were compared with control periods; taurocholate caused a relative increase in volume of 1 ml and approximately a fourfold increase in the hydrogen ion and sodium ion concentrations and the sodium ion flux. Changes in the hydrogen ion flux were smaller and, in some experiments, insignificant. Change in the hydrogen ion flux is less sensitive than the other parameters as an indicator of minimal mucosal damage.", "contents": "Some minimal effects of bile acid on canine gastric mucosa in Heidenhain pouches. The gastric mucosa in four canine Heidenhain pouches was damaged with sodium taurocholate in a concentration which was just sufficient in each dog to produce consistent changes. Solutions were placed in the pouches and changes in the volume, concentrations, and fluxes of both hydrogen ion and sodium ion were measured before and during exposure to taurocholate. Changes which occurred with taurocholate were compared with control periods; taurocholate caused a relative increase in volume of 1 ml and approximately a fourfold increase in the hydrogen ion and sodium ion concentrations and the sodium ion flux. Changes in the hydrogen ion flux were smaller and, in some experiments, insignificant. Change in the hydrogen ion flux is less sensitive than the other parameters as an indicator of minimal mucosal damage."}
{"id": "PMID:7955", "title": "Stability of frozen solutions of cefazolin sodium.", "content": "The stability of frozen solutions of cefazolin sodium was investigated in nine commonly used diluents at concentrations of 1 g with 2.5 ml, 500 mg with 100 ml and 10 g with 45 ml in both glass and polyvinylchloride plastic containers. The diluents were: Water for Injection USP; 0.9% Sodium Chloride Injection USP; 5% Dextrose Injection USP (D5W); D5W with 0.02% sodium bicarbonate; D5W in Lactated Ringer's Injection USP; Lactated Ringer's Injection USP; Ionosol B in D5W; Normasol M in D5W; and Plasmalyte in D5W. Frozen cefazolin sodium solutions, containing Water for Injection USP, 5% Dextrose Inection USP or 0.9% Sodium Chloride Injection USP as the diluents, retained more than 90% of labeled potency for up to 26 weeks when frozen within one hour after reconstitution and held at -10 C or -20 C. Frozen cefazolin sodium solutions, made with other diluents, were stable for up to four weeks when frozen within one hour after reconstitution and held at -10 C.", "contents": "Stability of frozen solutions of cefazolin sodium. The stability of frozen solutions of cefazolin sodium was investigated in nine commonly used diluents at concentrations of 1 g with 2.5 ml, 500 mg with 100 ml and 10 g with 45 ml in both glass and polyvinylchloride plastic containers. The diluents were: Water for Injection USP; 0.9% Sodium Chloride Injection USP; 5% Dextrose Injection USP (D5W); D5W with 0.02% sodium bicarbonate; D5W in Lactated Ringer's Injection USP; Lactated Ringer's Injection USP; Ionosol B in D5W; Normasol M in D5W; and Plasmalyte in D5W. Frozen cefazolin sodium solutions, containing Water for Injection USP, 5% Dextrose Inection USP or 0.9% Sodium Chloride Injection USP as the diluents, retained more than 90% of labeled potency for up to 26 weeks when frozen within one hour after reconstitution and held at -10 C or -20 C. Frozen cefazolin sodium solutions, made with other diluents, were stable for up to four weeks when frozen within one hour after reconstitution and held at -10 C."}
{"id": "PMID:7957", "title": "Takayasu's arteritis and congenital coarctation of the descending thoracic and abdominal aorta: a critical review.", "content": "A critical reappraisal of the clinical, arteriographic, and pathologic features of Takayasu's arteritis and so-called congenital aortic coarctations at atypical sites is presented. It is concluded that as an isolated cardiovascular abnormality, cases of atypical congenital coarctations of the descending thoracic and abdominal aorta are probably rare. The majority of atypical aortic coarctations previously reported in the United States and Europe as congenital lesions apparently represent unrecognized cases of Takayasu's arteritis.", "contents": "Takayasu's arteritis and congenital coarctation of the descending thoracic and abdominal aorta: a critical review. A critical reappraisal of the clinical, arteriographic, and pathologic features of Takayasu's arteritis and so-called congenital aortic coarctations at atypical sites is presented. It is concluded that as an isolated cardiovascular abnormality, cases of atypical congenital coarctations of the descending thoracic and abdominal aorta are probably rare. The majority of atypical aortic coarctations previously reported in the United States and Europe as congenital lesions apparently represent unrecognized cases of Takayasu's arteritis."}
{"id": "PMID:7958", "title": "Multiple gastric polyps and parathyroid adenomas. Report of two cases.", "content": "Two cases of multiple gastric polyps associated with parathyroid adenomas are presented. A review of the literature revealed four patients with multiple gastric polyps and multiple endocrine adenomatosis. The possiblity of multiple gastric polyps as a variant of the MEA syndrome complex is explored. Emphasis is placed on the need for thorough endocrine evaluation in patients with multiple gastric polyps.", "contents": "Multiple gastric polyps and parathyroid adenomas. Report of two cases. Two cases of multiple gastric polyps associated with parathyroid adenomas are presented. A review of the literature revealed four patients with multiple gastric polyps and multiple endocrine adenomatosis. The possiblity of multiple gastric polyps as a variant of the MEA syndrome complex is explored. Emphasis is placed on the need for thorough endocrine evaluation in patients with multiple gastric polyps."}
{"id": "PMID:7959", "title": "Percutaneous method for arterial and venous monitoring.", "content": "A new technic for monitoring blood gases or venous and arterial pressure is described. Catheters are inserted by percutaneous puncture and guided into the femoral and iliac vessels with minimal manipulation. This rapid, simple technic has been used in more than 100 patients without a major complication.", "contents": "Percutaneous method for arterial and venous monitoring. A new technic for monitoring blood gases or venous and arterial pressure is described. Catheters are inserted by percutaneous puncture and guided into the femoral and iliac vessels with minimal manipulation. This rapid, simple technic has been used in more than 100 patients without a major complication."}
{"id": "PMID:7960", "title": "Quantitation of local acidosis and hypoxia produced by infection.", "content": "Increased strength of healing incisions infected with E coli was demonstrated in this experiment. Efforts to measure respiratory gas tensions and pH in these incisions were unsuccessful. Therefore, these moieties were measured in normal and infected wound fluid contained in implanted wire cylinders. The wound fluid from infected cylinders was consistently more acidotic and had a lower pO2 and a higher pCO2 than fluid from unifected wound cylinders.", "contents": "Quantitation of local acidosis and hypoxia produced by infection. Increased strength of healing incisions infected with E coli was demonstrated in this experiment. Efforts to measure respiratory gas tensions and pH in these incisions were unsuccessful. Therefore, these moieties were measured in normal and infected wound fluid contained in implanted wire cylinders. The wound fluid from infected cylinders was consistently more acidotic and had a lower pO2 and a higher pCO2 than fluid from unifected wound cylinders."}
{"id": "PMID:7963", "title": "[Controlled hypotension with sodium nitroprusside (author's transl)].", "content": "Sodium notroprusside (Nipruss), in comparison with halothane and trimetaphan a very suitable hypotensive drug, was examined for blood pressure lowering efficency and possible side effects. For this purpose 7 patients (group 1) underwent \"classical\" hypotension during neurosurgical procedures. In 5 cases (group 2) nitroprusside infusion was needed for therapy of hypertensive crisis during vascular surgery. In all patients the hypotensive action was prompt and sufficient. Low blood pressure was accompanied by a 22.5% rise of heart rate and a 66% fall of central venous pressure. The development of mild metabolic acidosis seemed to be without clinical importance. The doses employed ranged from 3 to 13 (grpup 1) and from 1.5 to 3.1 gamma/kg/min (group 2). Sodium nitroprusside proved a very useful hypotensive drug, fitting well with the needs of modern anaesthesia.", "contents": "[Controlled hypotension with sodium nitroprusside (author's transl)]. Sodium notroprusside (Nipruss), in comparison with halothane and trimetaphan a very suitable hypotensive drug, was examined for blood pressure lowering efficency and possible side effects. For this purpose 7 patients (group 1) underwent \"classical\" hypotension during neurosurgical procedures. In 5 cases (group 2) nitroprusside infusion was needed for therapy of hypertensive crisis during vascular surgery. In all patients the hypotensive action was prompt and sufficient. Low blood pressure was accompanied by a 22.5% rise of heart rate and a 66% fall of central venous pressure. The development of mild metabolic acidosis seemed to be without clinical importance. The doses employed ranged from 3 to 13 (grpup 1) and from 1.5 to 3.1 gamma/kg/min (group 2). Sodium nitroprusside proved a very useful hypotensive drug, fitting well with the needs of modern anaesthesia."}
{"id": "PMID:7964", "title": "[Ariway resistance in intensive care patients (author's transl)].", "content": "With the modified interrupition technique airway resistance and tidal volume of bed-ridden patients can be measured simultaneously. This objective measure causes no distress to the patient. The effect of Noleptan on tidal volume and airway resistance has been studied in 28 patients (most of them have been unconscious). Tidal volume was improved significantly leading to an increases of arterial pO2. The bronchial airway resistance was uneffected. Our findings underline the postive experiences with Noleptan in clinical trial of intensive care.", "contents": "[Ariway resistance in intensive care patients (author's transl)]. With the modified interrupition technique airway resistance and tidal volume of bed-ridden patients can be measured simultaneously. This objective measure causes no distress to the patient. The effect of Noleptan on tidal volume and airway resistance has been studied in 28 patients (most of them have been unconscious). Tidal volume was improved significantly leading to an increases of arterial pO2. The bronchial airway resistance was uneffected. Our findings underline the postive experiences with Noleptan in clinical trial of intensive care."}
{"id": "PMID:7965", "title": "[Studies on the stability of local anaesthetics containing adrenaline (author's transl)].", "content": "Local toxic reactions from adrenaline following nerve block anaesthesia have been observed by many workers. Because of this potential danger we studied the changes of anaesthetic solutions containing adrenaline during a longer storage period. The measurements show a drop in the pH of the solutions caused by decomposition of adrenaline. This effect of storage is not detectable with the naked eye but makes analytical procedures necessary. Molecular oxygen and light decompose the solutions rapidly. After a storage period of some months the acidity of the solutions is comparable to concentrated acetic acid, a fact which could lead to local complications.", "contents": "[Studies on the stability of local anaesthetics containing adrenaline (author's transl)]. Local toxic reactions from adrenaline following nerve block anaesthesia have been observed by many workers. Because of this potential danger we studied the changes of anaesthetic solutions containing adrenaline during a longer storage period. The measurements show a drop in the pH of the solutions caused by decomposition of adrenaline. This effect of storage is not detectable with the naked eye but makes analytical procedures necessary. Molecular oxygen and light decompose the solutions rapidly. After a storage period of some months the acidity of the solutions is comparable to concentrated acetic acid, a fact which could lead to local complications."}
{"id": "PMID:7966", "title": "[The calculation of the oxygen saturation as function of pO2, pH, temperature and base deviation (author's transl)].", "content": "The paper describes a mathematical relationship between the partial pressure of oxygen and the oxygen saturation of the blood which approximates the standard oxygen dissociation curve. This approximation is based on a consideration of the electro-chemical equilibria of the reduced and the oxygenated blood.", "contents": "[The calculation of the oxygen saturation as function of pO2, pH, temperature and base deviation (author's transl)]. The paper describes a mathematical relationship between the partial pressure of oxygen and the oxygen saturation of the blood which approximates the standard oxygen dissociation curve. This approximation is based on a consideration of the electro-chemical equilibria of the reduced and the oxygenated blood."}
{"id": "PMID:7967", "title": "Anaesthesia with sulfentanil-analgesia in carotid and vertebral arteriography. A comparison with fentanyl.", "content": "The effects of the analgesics sulfentanil (R 30730) and fentanyl, on autonimic stability, cardiovascular stability, respiratory depression and post-operative behaviour were compared in a standardised anaesthetic technique. Twenty-nine patients undergoing neurological arteriographies, were treated with one or more doses of 0.5 mg fentanyl; 22 patients were treated with an initial dose of 0.05 mg of sulfentanil followed by repeat injections of 0.025 mg, when necessary. The analgesic potency of sulfentanil proved to be 12 times that of fentanyl while (in contrast to fentanyl), the duration of the respiratory depression after sulfentanil did not differ significantly from the duration of optimal analgesia. The effects of both drugs on blood pressure and heart rate were minimal; autonomic stability was excellent. No serious side effects were seen in any of the patients. After sulfentanil analgesia the patients were more rapidly awake and lucid, than after fentanyl-analgesia. Further investigations with this new and promising drug seem to be of great interest.", "contents": "Anaesthesia with sulfentanil-analgesia in carotid and vertebral arteriography. A comparison with fentanyl. The effects of the analgesics sulfentanil (R 30730) and fentanyl, on autonimic stability, cardiovascular stability, respiratory depression and post-operative behaviour were compared in a standardised anaesthetic technique. Twenty-nine patients undergoing neurological arteriographies, were treated with one or more doses of 0.5 mg fentanyl; 22 patients were treated with an initial dose of 0.05 mg of sulfentanil followed by repeat injections of 0.025 mg, when necessary. The analgesic potency of sulfentanil proved to be 12 times that of fentanyl while (in contrast to fentanyl), the duration of the respiratory depression after sulfentanil did not differ significantly from the duration of optimal analgesia. The effects of both drugs on blood pressure and heart rate were minimal; autonomic stability was excellent. No serious side effects were seen in any of the patients. After sulfentanil analgesia the patients were more rapidly awake and lucid, than after fentanyl-analgesia. Further investigations with this new and promising drug seem to be of great interest."}
{"id": "PMID:7978", "title": "[Hyperbaric oxygen therapy in cerebral circulatory insufficiency].", "content": "From a study bearing upon 26 patients suffering from a cerebral circulatory insufficiency induced by a stenosis or a thrombosis, the writers analyse the part played by Hyperbare Oxygen in the neurologic evolution. The defining of the efficacy criteria enabled them to determine whenever this part was prevalent and obvious (that's to say in 20 p. 100 of the cases). However, in the other cases it was hard to decide whether Hyperbare Oxygen played any part. Only functional lesions are liable to benefit from this therapy which seems mainly useful to cover the period of circulatory adaptation at a time when supply circulations may come into play. The difficulty to appreciate the importance of supply circulations urges on to treat this type of patients early enough in a systematic way and all the more so as they are young.", "contents": "[Hyperbaric oxygen therapy in cerebral circulatory insufficiency]. From a study bearing upon 26 patients suffering from a cerebral circulatory insufficiency induced by a stenosis or a thrombosis, the writers analyse the part played by Hyperbare Oxygen in the neurologic evolution. The defining of the efficacy criteria enabled them to determine whenever this part was prevalent and obvious (that's to say in 20 p. 100 of the cases). However, in the other cases it was hard to decide whether Hyperbare Oxygen played any part. Only functional lesions are liable to benefit from this therapy which seems mainly useful to cover the period of circulatory adaptation at a time when supply circulations may come into play. The difficulty to appreciate the importance of supply circulations urges on to treat this type of patients early enough in a systematic way and all the more so as they are young."}
{"id": "PMID:7979", "title": "[Autotransfusion in experimental hemoperitoneum. Hematologic study].", "content": "In order to study the hematologic repercussions of pre-operative autotransfusion, ruptures were made in experimental spleens followed by retransfusion after intraperitoneal barbotage of long duration in 8 dogs. This was performed without any heparinization. The following facts could be established:--although the blood shed was rich in red globules, it presented major alterations with a loss of clotting agents and evidence of fibrinogenic degradating elements.--A study of the blood during the transfusion and after the intervention did not reveal any intravascular coagulation but only a loss of fibrinogen and thrombocytes proportional to the amount of autotransfused blood. The limit of haemostatic tolerance with no supply of external blood was an autotransfusion ranging about 75 p. 100 of the initial blood volume.", "contents": "[Autotransfusion in experimental hemoperitoneum. Hematologic study]. In order to study the hematologic repercussions of pre-operative autotransfusion, ruptures were made in experimental spleens followed by retransfusion after intraperitoneal barbotage of long duration in 8 dogs. This was performed without any heparinization. The following facts could be established:--although the blood shed was rich in red globules, it presented major alterations with a loss of clotting agents and evidence of fibrinogenic degradating elements.--A study of the blood during the transfusion and after the intervention did not reveal any intravascular coagulation but only a loss of fibrinogen and thrombocytes proportional to the amount of autotransfused blood. The limit of haemostatic tolerance with no supply of external blood was an autotransfusion ranging about 75 p. 100 of the initial blood volume."}
{"id": "PMID:7980", "title": "[Resistance test to streptokinase. Its value in the establishing of a thrombolytic treatment using this enzyme].", "content": "The reckoning of the rate of serous anti-streptokinase (ASK) evidenced that 8 p. 100 of the test-sample presented a distinct resistance to Streptokinase (SK), and that this percentage could be more important under certain pathological circumstances. On account of this fact and also because SK injectable preparations may offer a variation in activity, the writers advocate a \"preliminary control in vitro\" by means of the resistance test to streptokinase that enables one to make sure, for each patient, of the biological efficacy of the drug and to specify the starting posology.", "contents": "[Resistance test to streptokinase. Its value in the establishing of a thrombolytic treatment using this enzyme]. The reckoning of the rate of serous anti-streptokinase (ASK) evidenced that 8 p. 100 of the test-sample presented a distinct resistance to Streptokinase (SK), and that this percentage could be more important under certain pathological circumstances. On account of this fact and also because SK injectable preparations may offer a variation in activity, the writers advocate a \"preliminary control in vitro\" by means of the resistance test to streptokinase that enables one to make sure, for each patient, of the biological efficacy of the drug and to specify the starting posology."}
{"id": "PMID:7975", "title": "Physostigmine reversal of sedation in parturients.", "content": "Parturients in whom meperidine HCl, propiomazine HCl, and scopolamine were used for analgesia and amnesia in labor and delivery were studied to determine the efficacy and safety of physostigmine reversal after delivery. Of a total of 120 patients, 108 received physostigmine salicylate at the completion of episiotomy closure, awakening in an average of 7.5 minutes compared with 137.8 in 12 controls. Physostigmine appears to be a safe, rapidly effective agent for reversing the prolonged somnolence of this sedation regimen.", "contents": "Physostigmine reversal of sedation in parturients. Parturients in whom meperidine HCl, propiomazine HCl, and scopolamine were used for analgesia and amnesia in labor and delivery were studied to determine the efficacy and safety of physostigmine reversal after delivery. Of a total of 120 patients, 108 received physostigmine salicylate at the completion of episiotomy closure, awakening in an average of 7.5 minutes compared with 137.8 in 12 controls. Physostigmine appears to be a safe, rapidly effective agent for reversing the prolonged somnolence of this sedation regimen."}
{"id": "PMID:7981", "title": "[Presentation of equipment: the monitor of cerebral function].", "content": "From a pair of parietal electrodes, an original apparatus--the monitor of cerebral function--gives a non-stop recording of the brain electric activity for frequencies ranging from 2 to 15 Hertz. It is at the moment less expensive than an ordinary EEG apparatus, easy to carry, to use and to read. The artefacts, interferences or technical defects are either totally eliminated or immediately detected thanks to a parallel graph. It is the first apparatus that has been conceived and used as a routine instrument for cerebral monitoring. It can be used in the Intensive Care Unit as well as in the Operating Theatre:--preventively, whenever there is a risk of an alteration in the cerebral circulation (CEC - extracorporal circulation - for instance - as a diagnosis, a prognosis or a therapy when there is a cerebral lesion (whatever the origin of it can be). The use of this apparatus (that has now become part of the daily routine at the London Hospital) has quickly proved indispensable and the common EEG is no longer being resorted to except upon very few occasions.", "contents": "[Presentation of equipment: the monitor of cerebral function]. From a pair of parietal electrodes, an original apparatus--the monitor of cerebral function--gives a non-stop recording of the brain electric activity for frequencies ranging from 2 to 15 Hertz. It is at the moment less expensive than an ordinary EEG apparatus, easy to carry, to use and to read. The artefacts, interferences or technical defects are either totally eliminated or immediately detected thanks to a parallel graph. It is the first apparatus that has been conceived and used as a routine instrument for cerebral monitoring. It can be used in the Intensive Care Unit as well as in the Operating Theatre:--preventively, whenever there is a risk of an alteration in the cerebral circulation (CEC - extracorporal circulation - for instance - as a diagnosis, a prognosis or a therapy when there is a cerebral lesion (whatever the origin of it can be). The use of this apparatus (that has now become part of the daily routine at the London Hospital) has quickly proved indispensable and the common EEG is no longer being resorted to except upon very few occasions."}
{"id": "PMID:7976", "title": "Clinical evaluation of injectable lorazepam as a premedicant: the effect on recall.", "content": "A double-blind comparison of lorazepam and placebo, lorazepam and pentobarbital, and a comparison of lorazepam IV drip versus lorazepam IV bolus as a premedicant showed this new agent to offer promise as a sedative premedicant. However, the potency of the drug demands caution, and its use for outpatient premedication is not recommended.", "contents": "Clinical evaluation of injectable lorazepam as a premedicant: the effect on recall. A double-blind comparison of lorazepam and placebo, lorazepam and pentobarbital, and a comparison of lorazepam IV drip versus lorazepam IV bolus as a premedicant showed this new agent to offer promise as a sedative premedicant. However, the potency of the drug demands caution, and its use for outpatient premedication is not recommended."}
{"id": "PMID:7982", "title": "[Value of moderate fentanyl dosage during anesthesis in abdominal surgery. Apropos of 100 cases].", "content": "Fentanyl was used in 100 abdominal surgical interventions, combined with droperidol or with diazepan, always with good results as far as analgesia was concerned. Tensional variations that occurred during the induction were quite small and disappeared during the filling up. In the course of the intervention, tensional variations were only met with subjects suffering from high blood pressure. The respiratory depression that went with analgesia did not constitute an obstacle but made it necessary to use artificial ventilation for the intervetion. The awakening was always quick, smooth, without any vomiting and was influenced neither by the time taken up by the intervention nor by the condition of the patient. No residual respiratory depression requiring the use of an anti-morphinic was noted. At the end of the study, fentanyl appears as a powerful analgesic, easy to use and successful in all the cases of abdominal surgery. Its effect does not last, a drawback that can be avoided by the use of an intravenous drip.", "contents": "[Value of moderate fentanyl dosage during anesthesis in abdominal surgery. Apropos of 100 cases]. Fentanyl was used in 100 abdominal surgical interventions, combined with droperidol or with diazepan, always with good results as far as analgesia was concerned. Tensional variations that occurred during the induction were quite small and disappeared during the filling up. In the course of the intervention, tensional variations were only met with subjects suffering from high blood pressure. The respiratory depression that went with analgesia did not constitute an obstacle but made it necessary to use artificial ventilation for the intervetion. The awakening was always quick, smooth, without any vomiting and was influenced neither by the time taken up by the intervention nor by the condition of the patient. No residual respiratory depression requiring the use of an anti-morphinic was noted. At the end of the study, fentanyl appears as a powerful analgesic, easy to use and successful in all the cases of abdominal surgery. Its effect does not last, a drawback that can be avoided by the use of an intravenous drip."}
{"id": "PMID:7977", "title": "Fluroxene (2, 2, 2-trifluorethyl vinyl ether) toxicity: a chemical aspect.", "content": "Fluroxene is highly toxic to several animal species. This toxicity is enhanced by induction of raised levels of hepatic microsomal enzymes. Experiments in rats are described which seek to assess the rleative contribution to this toxicity of the individual component groups of the fluroxene molecule. Though results point to the trifluoroethyl moiety of fluroxene as that aspect of the molecule most responsible for the observed mortality, reduction of the vinyl group modifies the pattern of liver injury. That the liver necrosis, manifest following fluroxene anesthesia in the presence of microsomal induction, is alone the direct cause of the acute death of experimental animals is questioned.", "contents": "Fluroxene (2, 2, 2-trifluorethyl vinyl ether) toxicity: a chemical aspect. Fluroxene is highly toxic to several animal species. This toxicity is enhanced by induction of raised levels of hepatic microsomal enzymes. Experiments in rats are described which seek to assess the rleative contribution to this toxicity of the individual component groups of the fluroxene molecule. Though results point to the trifluoroethyl moiety of fluroxene as that aspect of the molecule most responsible for the observed mortality, reduction of the vinyl group modifies the pattern of liver injury. That the liver necrosis, manifest following fluroxene anesthesia in the presence of microsomal induction, is alone the direct cause of the acute death of experimental animals is questioned."}
{"id": "PMID:7983", "title": "[Attempt at a mathematical definition of pachycurare dosage. Application for pancuronium and AH 8165].", "content": "Correlations among the elements indispensable to the choice of an average dose of pachycurare are established for surgical needs. Weight and duration of the surgery jointly allow to foresee with approximately 80 p. 100 accuracy the effective dose required for a surgical curarization controlled according to clinical and electromyographical criteria. After calculation of the average consumption of pachycurare per unit of time, a group of curves is established by successive integrations of additional doses representing a family of parabolae corresponding to a second-degree equation: P = alpha + beta t + gamma t2 where P: the cumulative dose for a determined period of time, per kg of body weight and thus total dose if t: the duration of the surgery, t: the time variable, alpha, beta and gamma: significant calculated coefficients. This analytical function established for the use of Pancuronium - bromide in surgery, is also being tried for the curarizing substance: AH.8165.", "contents": "[Attempt at a mathematical definition of pachycurare dosage. Application for pancuronium and AH 8165]. Correlations among the elements indispensable to the choice of an average dose of pachycurare are established for surgical needs. Weight and duration of the surgery jointly allow to foresee with approximately 80 p. 100 accuracy the effective dose required for a surgical curarization controlled according to clinical and electromyographical criteria. After calculation of the average consumption of pachycurare per unit of time, a group of curves is established by successive integrations of additional doses representing a family of parabolae corresponding to a second-degree equation: P = alpha + beta t + gamma t2 where P: the cumulative dose for a determined period of time, per kg of body weight and thus total dose if t: the duration of the surgery, t: the time variable, alpha, beta and gamma: significant calculated coefficients. This analytical function established for the use of Pancuronium - bromide in surgery, is also being tried for the curarizing substance: AH.8165."}
{"id": "PMID:7984", "title": "[Parenteral use of a solution-emulsion following digestive surgery].", "content": "A post-operative use of the calorico-nitrogenous mixture: Triv\u00e9 1000 was carried out in 25 patients after digestive surgery. The prescribed dose of this lipidic emulsion was 1,36 1 for an average period of four days. A study of the results led to establish the following facts:--a 55 p. cent increase in the nitrogen retention in comparison with a control series of ten patients and from (J o) the day of the intervention to (J F) the day when the treatment was stopped. Besides, the duration of the treatment did not seem to modify this balance, at least within the limits of the period of use. On the other hand, the quantity of EB 51 was a determining factor since 2000 ml were necessary to obtain a positive nitrogen balance (+ 0.96 g).--a very small rise in the amino-acid serous rate. It appeared in 14 patients and, supplied by EB 51, 3 other amino-acids increased their proportion spontaneously (Asp.--Gluc.--Tau.).--a reduction of the rate of 5 amino-acids, one of which, however, (Arginine) was being supplied by the drip. The variations were never statistically significant but for the Phenylalanine rate increase.--a non-systematic variation in the blood proteids that decreased as far as total proteids and albumin were concerned and that increased as far as globulins alpha1 and alpha2 were concerned.--Finally, no variations in the serous graphic record of lipid levels were noted, neither in the average of figures, nor in the analyses carried out after each bottle. Besides, it must be added that the tolerance of the product was excellent both on a general level (very few cases of intolerance: 4) and on the level of the plasma turbidimetry which did not reveal and chylomicrons except in one case. Therefore Triv\u00e9 1000 proved to be an interesting nutrient combinatin quite suited to a parenteral feeding because of its high caloric power. The necessity of a calories/g/nitrogen ratio from 100 to 200 corresponding to 2000 ml of EB 51 was once more evidenced. Therefore such a dose (for lack of a protein assimilation) allows for a nitrogen retention important enough to prevent an excessive consumption of the body proteinic reserves. Such doses are perfectly tolerated both on the general and metabolic levels (mainly on the lipometabolic one).", "contents": "[Parenteral use of a solution-emulsion following digestive surgery]. A post-operative use of the calorico-nitrogenous mixture: Triv\u00e9 1000 was carried out in 25 patients after digestive surgery. The prescribed dose of this lipidic emulsion was 1,36 1 for an average period of four days. A study of the results led to establish the following facts:--a 55 p. cent increase in the nitrogen retention in comparison with a control series of ten patients and from (J o) the day of the intervention to (J F) the day when the treatment was stopped. Besides, the duration of the treatment did not seem to modify this balance, at least within the limits of the period of use. On the other hand, the quantity of EB 51 was a determining factor since 2000 ml were necessary to obtain a positive nitrogen balance (+ 0.96 g).--a very small rise in the amino-acid serous rate. It appeared in 14 patients and, supplied by EB 51, 3 other amino-acids increased their proportion spontaneously (Asp.--Gluc.--Tau.).--a reduction of the rate of 5 amino-acids, one of which, however, (Arginine) was being supplied by the drip. The variations were never statistically significant but for the Phenylalanine rate increase.--a non-systematic variation in the blood proteids that decreased as far as total proteids and albumin were concerned and that increased as far as globulins alpha1 and alpha2 were concerned.--Finally, no variations in the serous graphic record of lipid levels were noted, neither in the average of figures, nor in the analyses carried out after each bottle. Besides, it must be added that the tolerance of the product was excellent both on a general level (very few cases of intolerance: 4) and on the level of the plasma turbidimetry which did not reveal and chylomicrons except in one case. Therefore Triv\u00e9 1000 proved to be an interesting nutrient combinatin quite suited to a parenteral feeding because of its high caloric power. The necessity of a calories/g/nitrogen ratio from 100 to 200 corresponding to 2000 ml of EB 51 was once more evidenced. Therefore such a dose (for lack of a protein assimilation) allows for a nitrogen retention important enough to prevent an excessive consumption of the body proteinic reserves. Such doses are perfectly tolerated both on the general and metabolic levels (mainly on the lipometabolic one)."}
{"id": "PMID:7985", "title": "[Complete parenteral alimentation after major digestive surgery using lEB 51-Triv\u00e9 1000].", "content": "The aim of this work is to study the tolerance and the effectiveness of a complete intravenous feeding with EB 51 - Trivemil in immediate post-operative period, in 40 patients undergoing major digestive surgery. The patients were divided into three groups:--first group: 25 patients were given daily an average of 2900 calories 1500 of which via the Trivemil, during the first four post-operative days.--Second group: 5 patients received the same daily caloric dose but because of local complications, drips were maintained until the 7th day.--Third group: 10 patients received an average of 3100 calories daily 2000 of which via the Trivemil. The tolerance was evaluated by a clinical observation (blood pressure - nausea - cutaneous manifestations - temperature) and by a biological observation (hemolysis - free hemoglobin - plasma clearing). The use and effectiveness of the nutrient was evaluated - globally - by a study of body weight according to the hydro-electrolytic balance and then - individually - by the balance of the intakes and secretions of the glucides, lipids and proteids. The tolerance was excellent in all the cases, the weight remained stable, the nitrogen retention was constant mainly in the third group where it seemed to depend on the initial total energetic intake.", "contents": "[Complete parenteral alimentation after major digestive surgery using lEB 51-Triv\u00e9 1000]. The aim of this work is to study the tolerance and the effectiveness of a complete intravenous feeding with EB 51 - Trivemil in immediate post-operative period, in 40 patients undergoing major digestive surgery. The patients were divided into three groups:--first group: 25 patients were given daily an average of 2900 calories 1500 of which via the Trivemil, during the first four post-operative days.--Second group: 5 patients received the same daily caloric dose but because of local complications, drips were maintained until the 7th day.--Third group: 10 patients received an average of 3100 calories daily 2000 of which via the Trivemil. The tolerance was evaluated by a clinical observation (blood pressure - nausea - cutaneous manifestations - temperature) and by a biological observation (hemolysis - free hemoglobin - plasma clearing). The use and effectiveness of the nutrient was evaluated - globally - by a study of body weight according to the hydro-electrolytic balance and then - individually - by the balance of the intakes and secretions of the glucides, lipids and proteids. The tolerance was excellent in all the cases, the weight remained stable, the nitrogen retention was constant mainly in the third group where it seemed to depend on the initial total energetic intake."}
{"id": "PMID:7987", "title": "[Corneal and lens deposits due to treatment by phenothiazine type neuroleptics].", "content": "The authors have studied the corneal and lens lesions which appeared following a prolonged treatment by phenothiazines. They examined 186 patients: 147 took phenothiazines of which 35 of them presented anterior segment alterations. It seems that all phenothiazines can be held responsible for the apparition of these lesions. At this point the authors evaluated the global dose of the various phenothiazines which were administered. The threshold at which the association of these lesions seem to appear, seems to be situated around 300 gr. The total quantity of phenothiazines which are absorbed seems to be a good measure of the risk of ocular toxicity. In the case of one patient they observed that his visual keenness was lowered due to the importance of his corneal and lens lesions.", "contents": "[Corneal and lens deposits due to treatment by phenothiazine type neuroleptics]. The authors have studied the corneal and lens lesions which appeared following a prolonged treatment by phenothiazines. They examined 186 patients: 147 took phenothiazines of which 35 of them presented anterior segment alterations. It seems that all phenothiazines can be held responsible for the apparition of these lesions. At this point the authors evaluated the global dose of the various phenothiazines which were administered. The threshold at which the association of these lesions seem to appear, seems to be situated around 300 gr. The total quantity of phenothiazines which are absorbed seems to be a good measure of the risk of ocular toxicity. In the case of one patient they observed that his visual keenness was lowered due to the importance of his corneal and lens lesions."}
{"id": "PMID:7988", "title": "[The effect of pH and partial pressure of oxygen on nitrification (author's transl)].", "content": "A mathematical model which describes the effect of pH and dissolved oxygen on growth and activity of Nitrosomonas and Nitrobacter in mixed culture is presented. A good fit is obtained between experimental data and theoretical curves computed with parameters estimated by independent methods. Experimental data together with simulation studies show that inadequate aeration induces a temporal shift of ammonium and nitrite oxidations resulting in a transient nitrite accumulation similar to that caused by an increase of temperature.", "contents": "[The effect of pH and partial pressure of oxygen on nitrification (author's transl)]. A mathematical model which describes the effect of pH and dissolved oxygen on growth and activity of Nitrosomonas and Nitrobacter in mixed culture is presented. A good fit is obtained between experimental data and theoretical curves computed with parameters estimated by independent methods. Experimental data together with simulation studies show that inadequate aeration induces a temporal shift of ammonium and nitrite oxidations resulting in a transient nitrite accumulation similar to that caused by an increase of temperature."}
{"id": "PMID:7989", "title": "[Nitric oxide production in rice soils (author's transl)].", "content": "Nitric oxide gas evolution from nitrite was studied in vitro in three rice soils by gas chromatography. Autoclaved soils showed an NO evolution when supplemented with nitrite. Yet, when temperature of incubation, soil pH, soil moisture content and nitrite concentration were varied in the three soils, and with addition of nitrite reductase inhibitors, it appeared in one soil that NO production was partially a biological process. Thus, NO formation was two times as high in non-sterile soil as in sterile soil, and decreased when the temperature increased. Optimal NO production occurred at about neutrality and increased with increasing soil moisture content; moreover, this NO formation increased much less than in the other two soils with increasing nitrite concentration. Finally, the first soil contained three times more denitrifying bacteria tolerating a high nitrite concentration (5 g/1) that the other soils.", "contents": "[Nitric oxide production in rice soils (author's transl)]. Nitric oxide gas evolution from nitrite was studied in vitro in three rice soils by gas chromatography. Autoclaved soils showed an NO evolution when supplemented with nitrite. Yet, when temperature of incubation, soil pH, soil moisture content and nitrite concentration were varied in the three soils, and with addition of nitrite reductase inhibitors, it appeared in one soil that NO production was partially a biological process. Thus, NO formation was two times as high in non-sterile soil as in sterile soil, and decreased when the temperature increased. Optimal NO production occurred at about neutrality and increased with increasing soil moisture content; moreover, this NO formation increased much less than in the other two soils with increasing nitrite concentration. Finally, the first soil contained three times more denitrifying bacteria tolerating a high nitrite concentration (5 g/1) that the other soils."}
{"id": "PMID:7994", "title": "[Effect of different pH values on the medium on the synthesis of antibiotics in the joint cultivation of Actinomyces levoris with yeasts].", "content": "Changes in the pH level of the fermentation medium used for preliminary cultivation of C. tropicalis were studied with respect to its initial aciditv or alkalinitv. When C. tropicalis was grown on the medium used for levorin fermentation with ph 5.1--10.3, the yeast changed it in 24 hours to the level of 6.2--7.9. As dependent on the initial pH values for cultivation of C. trophicalis, production of levorin on subsequent inoculation of Act. levoris changed. The antibiotic activity increased and ranged within 120--178% of the control. Synthesis of levoristatin, a non-polyenic antibiotic equally increased under such conditions and ranged within 153--163% of the control. The pH values of 9.4--10.3 of the initial fermentation medium were optimal for mixed cultivation of Act levoris and C. tropicalis and maxium production of levorin and levoristatin.", "contents": "[Effect of different pH values on the medium on the synthesis of antibiotics in the joint cultivation of Actinomyces levoris with yeasts]. Changes in the pH level of the fermentation medium used for preliminary cultivation of C. tropicalis were studied with respect to its initial aciditv or alkalinitv. When C. tropicalis was grown on the medium used for levorin fermentation with ph 5.1--10.3, the yeast changed it in 24 hours to the level of 6.2--7.9. As dependent on the initial pH values for cultivation of C. trophicalis, production of levorin on subsequent inoculation of Act. levoris changed. The antibiotic activity increased and ranged within 120--178% of the control. Synthesis of levoristatin, a non-polyenic antibiotic equally increased under such conditions and ranged within 153--163% of the control. The pH values of 9.4--10.3 of the initial fermentation medium were optimal for mixed cultivation of Act levoris and C. tropicalis and maxium production of levorin and levoristatin."}
{"id": "PMID:7995", "title": "[Effect of the initial pH value of the medium on the growth of Streptococcus lactis and the biosynthesis of nisin].", "content": "The effect of the initial pH value of the medium within 4.0 to 6.6 on the growth of Str. lactis and biosynthesis of nicin was studied. It was found that at the initial pH 4.0--4.5 of the medium the growth of the culture was poor, i.e. 11--14% of the control (initiral pH 6.6). With an increase in the value of the initial pH at least to 5.0 the growth of Str. lactis also increased. At the initial pH 4.0 no biosynthesis of nicin was observed. Under the experimental conditions the antibiotic synthesis by tr. lactic started at the initial pH being equal to 4.5 and reached its maximum at pH 6.6.", "contents": "[Effect of the initial pH value of the medium on the growth of Streptococcus lactis and the biosynthesis of nisin]. The effect of the initial pH value of the medium within 4.0 to 6.6 on the growth of Str. lactis and biosynthesis of nicin was studied. It was found that at the initial pH 4.0--4.5 of the medium the growth of the culture was poor, i.e. 11--14% of the control (initiral pH 6.6). With an increase in the value of the initial pH at least to 5.0 the growth of Str. lactis also increased. At the initial pH 4.0 no biosynthesis of nicin was observed. Under the experimental conditions the antibiotic synthesis by tr. lactic started at the initial pH being equal to 4.5 and reached its maximum at pH 6.6."}
{"id": "PMID:7996", "title": "[Study of E. coli penicillin amidase. The pH dependence of the equilibrium constant of the enzymatic hydrolysis of benzylpenicillin].", "content": "The equilibrium constant for penicillin amidase-catalyzed hydrolysis of benzylpenicillin(Keg =3.00 +/- 0.24 x 10(-3) M at pH 5.0) and the ionization constants for phenylacetic acid (PAA) and the amino groups of 6-aminopenicillanic acid (6-APA) were determined (4.20 and 4.60 under conditions of the kinetic experiments respectively). The experimental data at pH 6.0 satisfactorily correlated with the theoretical pH-dependence for Keg constructed according to the hypothesis that benzylpenicillin synthesis has a thermodynamic optimum at pH 4.4 equal to a half-sum of the pK values for the carboxylic and amino groups of the PAA and 6-APA respectively.", "contents": "[Study of E. coli penicillin amidase. The pH dependence of the equilibrium constant of the enzymatic hydrolysis of benzylpenicillin]. The equilibrium constant for penicillin amidase-catalyzed hydrolysis of benzylpenicillin(Keg =3.00 +/- 0.24 x 10(-3) M at pH 5.0) and the ionization constants for phenylacetic acid (PAA) and the amino groups of 6-aminopenicillanic acid (6-APA) were determined (4.20 and 4.60 under conditions of the kinetic experiments respectively). The experimental data at pH 6.0 satisfactorily correlated with the theoretical pH-dependence for Keg constructed according to the hypothesis that benzylpenicillin synthesis has a thermodynamic optimum at pH 4.4 equal to a half-sum of the pK values for the carboxylic and amino groups of the PAA and 6-APA respectively."}
{"id": "PMID:7997", "title": "Formation of beta-lactamase in Bacteroides fragilis: cell-bound and extracellular activity.", "content": "Nine strains of Bacteroides fragilis were cultivated in stirred fermentors and tested for their ability to produce beta-lactamase. There was a correlation between formation of beta-lactamase and high values of the minimal inhibitory concentration against beta-lactam antibiotics. B. fragilis strain B70 was used for optimizing the production of beta-lactamase. The highest bacterial yield was obtained in a proteose peptone-yeast extract medium. Optimal conditions for growth and beta-lactamase production were obtained at 37 C and pH 7.0. The beta-lactamase was released into the surrounding medium during the growth period to about 50%. Osmotic shock released about 20% of the total activity, and remaining activity was found in the cytoplasmic fraction. Substrate profile studies on four beta-lactamase-producing strains showed that the enzymes were mainly cephalosporinases. They are inhibited by cloxacillin, p-chloromercuribenzoate, and iodine. Analytical isoelectric focusing in polyacrylamide gel gave an isoelectric point of 4.9 +/- 0.2 for three of the strains and 5.6 +/- 0.2 for one. Comparison with beta-lactamases from aerobic gram-negative species with regard to isoelectric points showed no similarities. Also the molecular weight of the beta-lactamase from strain B70 of 43,000 indicates that this is a new class of beta-lactamase.", "contents": "Formation of beta-lactamase in Bacteroides fragilis: cell-bound and extracellular activity. Nine strains of Bacteroides fragilis were cultivated in stirred fermentors and tested for their ability to produce beta-lactamase. There was a correlation between formation of beta-lactamase and high values of the minimal inhibitory concentration against beta-lactam antibiotics. B. fragilis strain B70 was used for optimizing the production of beta-lactamase. The highest bacterial yield was obtained in a proteose peptone-yeast extract medium. Optimal conditions for growth and beta-lactamase production were obtained at 37 C and pH 7.0. The beta-lactamase was released into the surrounding medium during the growth period to about 50%. Osmotic shock released about 20% of the total activity, and remaining activity was found in the cytoplasmic fraction. Substrate profile studies on four beta-lactamase-producing strains showed that the enzymes were mainly cephalosporinases. They are inhibited by cloxacillin, p-chloromercuribenzoate, and iodine. Analytical isoelectric focusing in polyacrylamide gel gave an isoelectric point of 4.9 +/- 0.2 for three of the strains and 5.6 +/- 0.2 for one. Comparison with beta-lactamases from aerobic gram-negative species with regard to isoelectric points showed no similarities. Also the molecular weight of the beta-lactamase from strain B70 of 43,000 indicates that this is a new class of beta-lactamase."}
{"id": "PMID:7998", "title": "Enzymatic hydrolysis of cephalosporin C by an extracellular acetylhydrolase of Cephalosporium acremonium.", "content": "Extracellular hydrolases from Cephalosporium acremonium were analyzed according to their ability to deacetylate the beta-lactam antibiotic cephalosporin C. One out of at least six hydrolases exhibits appreciable cephalosporin C acetylhydrolase (CAH) activity. This enzyme was separated from other hydrolases and purified 220-fold. The purified CAH has a relatively low affinity for cephalosporin C (K(m), 20 mM) and is strongly inhibited by diisopropylfluorophosphate and less markedly affected by fluoride. Addition of glucose, maltose, and sucrose to the culture broth suppresses CAH production, whereas glycerol and succinate have no effect. Verrucarin A prevented the enzyme from appearing in the medium, which indicates the necessity of protein synthesis for CAH formation. When 1-thio-d-glucose was added to the culture medium, the results suggested that this glucose analogue is able to inhibit CAH synthesis. Our data provide evidence for a regulation of CAH synthesis similar to the catabolite repression system in bacteria.", "contents": "Enzymatic hydrolysis of cephalosporin C by an extracellular acetylhydrolase of Cephalosporium acremonium. Extracellular hydrolases from Cephalosporium acremonium were analyzed according to their ability to deacetylate the beta-lactam antibiotic cephalosporin C. One out of at least six hydrolases exhibits appreciable cephalosporin C acetylhydrolase (CAH) activity. This enzyme was separated from other hydrolases and purified 220-fold. The purified CAH has a relatively low affinity for cephalosporin C (K(m), 20 mM) and is strongly inhibited by diisopropylfluorophosphate and less markedly affected by fluoride. Addition of glucose, maltose, and sucrose to the culture broth suppresses CAH production, whereas glycerol and succinate have no effect. Verrucarin A prevented the enzyme from appearing in the medium, which indicates the necessity of protein synthesis for CAH formation. When 1-thio-d-glucose was added to the culture medium, the results suggested that this glucose analogue is able to inhibit CAH synthesis. Our data provide evidence for a regulation of CAH synthesis similar to the catabolite repression system in bacteria."}
{"id": "PMID:7999", "title": "Autolysis of high-GC isolates of Pseudomonas putrefaciens.", "content": "High-GC isolates of P. putrefaciens undergo extensive autolysis after growth, resulting in a marked decrease in turbidity and the release of high-molecular-weight DNA which imparts a high viscosity to culture broths. The native DNA released is resistant to attack by the exocellular DNase activity of the culture broths. Autolysis is inhibited by a pH of 6.0 and the presence of 0.001 M Mg++ or Ca++, and is enhanced by elevated pH values and temperatures. This autolytic phenomenon in broth cultures readily distinguishes high- from low-GC isolates. The latter do not exhibit autolysis.", "contents": "Autolysis of high-GC isolates of Pseudomonas putrefaciens. High-GC isolates of P. putrefaciens undergo extensive autolysis after growth, resulting in a marked decrease in turbidity and the release of high-molecular-weight DNA which imparts a high viscosity to culture broths. The native DNA released is resistant to attack by the exocellular DNase activity of the culture broths. Autolysis is inhibited by a pH of 6.0 and the presence of 0.001 M Mg++ or Ca++, and is enhanced by elevated pH values and temperatures. This autolytic phenomenon in broth cultures readily distinguishes high- from low-GC isolates. The latter do not exhibit autolysis."}
{"id": "PMID:8000", "title": "Microbial metabolism of ethylene.", "content": "The ethylene-oxidizing strain E20 was grown on different carbon sources to obtain information on the metabolism of ethylene from simultaneous adaptation studies and from measurements of specific activities of enzymes in cell-free extracts. From the simultaneous adaptation studies it was concluded that ethylene oxide is a product of ethylene catabolism. The bacterium was also able to grow on the epoxide. From a comparison of the specific activities of isocitrate lyase and malate synthetase in different extracts it was concluded that the glyoxylate cycle was involved in the metabolism of ethylene, indicating that acetyl-CoA is a metabolite of ethylene catabolism. The sequence of reactions leading from ethylene oxide to acetyl-CoA could not be established from the simultaneous adaptation experiments and the enzyme activities in extracts.", "contents": "Microbial metabolism of ethylene. The ethylene-oxidizing strain E20 was grown on different carbon sources to obtain information on the metabolism of ethylene from simultaneous adaptation studies and from measurements of specific activities of enzymes in cell-free extracts. From the simultaneous adaptation studies it was concluded that ethylene oxide is a product of ethylene catabolism. The bacterium was also able to grow on the epoxide. From a comparison of the specific activities of isocitrate lyase and malate synthetase in different extracts it was concluded that the glyoxylate cycle was involved in the metabolism of ethylene, indicating that acetyl-CoA is a metabolite of ethylene catabolism. The sequence of reactions leading from ethylene oxide to acetyl-CoA could not be established from the simultaneous adaptation experiments and the enzyme activities in extracts."}
{"id": "PMID:8001", "title": "Characterization of the neoagarotetra-ase and neoagarobiase of Cytophaga flevensis.", "content": "The degradation of neoagarotetraose and neoagarobiose by Cytophaga flevensis was investigated. The organism possesses an enzyme that hydrolyzes the tetramer by cleavage of its central beta-galactosidic linkage. The product of this reaction, neoagarobiose, is further hydrolyzed enzymatically to D-galactose and 3,6-anhydro-L-galactose. Both enzyme activities were localized in the cytoplasm. Attempts were made to partially purify the respective enzymes and although a 30-40 fold-purification was achieved, the final preparation contained both neoagarotetra-ase and neoagarobiase activities. Evidence was obtained that these activities were due to different enzymes. Neoagarotetra-ase is highly specific for oligosaccharides containing neoagarobiose units; the rate of hydrolysis is greatest with neoagarotetraose. It cannot hydrolyze pyruvated neoagarotetraose. Optimal conditions for its activity were pH 7.0 and 25 C. Neoagarobiase hydrolyzes only neoagarobiose and neoagarobiitol and optimal conditions for activity were pH 6.75 and 25 C. Both enzymes were inhibited by Ag+, Hg2+ and Zn2+ ions and by p-CMB, which indicates that thiol groups are present in their active centres. Both enzymes were induced by neoagaro-oligosaccharides and melibiose and were repressed when glucose was added to the medium. Neoagarobiase was also induced by D-galacturonic acid. In continuous culture, the rate of enzyme production was maximal at a dilution rate of 0.1 h-1.", "contents": "Characterization of the neoagarotetra-ase and neoagarobiase of Cytophaga flevensis. The degradation of neoagarotetraose and neoagarobiose by Cytophaga flevensis was investigated. The organism possesses an enzyme that hydrolyzes the tetramer by cleavage of its central beta-galactosidic linkage. The product of this reaction, neoagarobiose, is further hydrolyzed enzymatically to D-galactose and 3,6-anhydro-L-galactose. Both enzyme activities were localized in the cytoplasm. Attempts were made to partially purify the respective enzymes and although a 30-40 fold-purification was achieved, the final preparation contained both neoagarotetra-ase and neoagarobiase activities. Evidence was obtained that these activities were due to different enzymes. Neoagarotetra-ase is highly specific for oligosaccharides containing neoagarobiose units; the rate of hydrolysis is greatest with neoagarotetraose. It cannot hydrolyze pyruvated neoagarotetraose. Optimal conditions for its activity were pH 7.0 and 25 C. Neoagarobiase hydrolyzes only neoagarobiose and neoagarobiitol and optimal conditions for activity were pH 6.75 and 25 C. Both enzymes were inhibited by Ag+, Hg2+ and Zn2+ ions and by p-CMB, which indicates that thiol groups are present in their active centres. Both enzymes were induced by neoagaro-oligosaccharides and melibiose and were repressed when glucose was added to the medium. Neoagarobiase was also induced by D-galacturonic acid. In continuous culture, the rate of enzyme production was maximal at a dilution rate of 0.1 h-1."}
{"id": "PMID:8002", "title": "Purification and some properties of an extracellular maltase from Bacillus subtilis.", "content": "Bacillus subtilis P-11, capable of producing extracellular maltase, was isolated from soil. Maximum enzyme production was obtained on a medium containing 2.0% methyl-alpha-D-glucose, 0.5% phytone, and 0.2% yeast extract. After the removal of cells, extracellular maltase was precipitated by ammonium sulfate (85% saturation). The enzyme was purified by using the following procedures: Sephadex G-200 column chromatography, diethylaminoethyl-Sephadex A-50 ion-exchange column chromatography, and a second Sephadex G-200 column chromatography. A highly purified maltase without amylase or proteinase activities was obtained. Some properties of the extracellular maltase were determined: optimum pH, 6.0; optimum temperature, 45 C, when the incubation time was 30 min; pH stability, within 5.5 to 6.5; heat stability, stable up to 45 C; isoelectric point, pH 6.0 (by gel-isoelectric focusing); molecular weight, 33,000 (by gel filtration with Sephadex G-200); substrate specificity: the relative rates of hydrolysis of maltose, maltotriose, isomaltose, and maltotetraose were 100:15:14:4, respectively, and there was no activity toward alkyl or aryl-alpha-D-glucosides, amylose, or other higher polymers. Transglucosylase activity was present. Glucose and tris(hydroxymethyl)aminomethane were competitive inhibitors with Ki values of 4.54 and 75.08 mM, respectively; cysteine was a noncompetitive inhibitor. Michaelis constants were 5 mM for maltose, 1 mM for maltoriose, and 10 mM for isomaltose. A plot of pKm (-log Km) versus pH revealed two deflection points, one each at 5.5 and 6.5; these probably corresponded to an imidazole group of a histidine residue in or near the active center; this assumption was supported by the strong inhibition of enzyme activity by rose bengal.", "contents": "Purification and some properties of an extracellular maltase from Bacillus subtilis. Bacillus subtilis P-11, capable of producing extracellular maltase, was isolated from soil. Maximum enzyme production was obtained on a medium containing 2.0% methyl-alpha-D-glucose, 0.5% phytone, and 0.2% yeast extract. After the removal of cells, extracellular maltase was precipitated by ammonium sulfate (85% saturation). The enzyme was purified by using the following procedures: Sephadex G-200 column chromatography, diethylaminoethyl-Sephadex A-50 ion-exchange column chromatography, and a second Sephadex G-200 column chromatography. A highly purified maltase without amylase or proteinase activities was obtained. Some properties of the extracellular maltase were determined: optimum pH, 6.0; optimum temperature, 45 C, when the incubation time was 30 min; pH stability, within 5.5 to 6.5; heat stability, stable up to 45 C; isoelectric point, pH 6.0 (by gel-isoelectric focusing); molecular weight, 33,000 (by gel filtration with Sephadex G-200); substrate specificity: the relative rates of hydrolysis of maltose, maltotriose, isomaltose, and maltotetraose were 100:15:14:4, respectively, and there was no activity toward alkyl or aryl-alpha-D-glucosides, amylose, or other higher polymers. Transglucosylase activity was present. Glucose and tris(hydroxymethyl)aminomethane were competitive inhibitors with Ki values of 4.54 and 75.08 mM, respectively; cysteine was a noncompetitive inhibitor. Michaelis constants were 5 mM for maltose, 1 mM for maltoriose, and 10 mM for isomaltose. A plot of pKm (-log Km) versus pH revealed two deflection points, one each at 5.5 and 6.5; these probably corresponded to an imidazole group of a histidine residue in or near the active center; this assumption was supported by the strong inhibition of enzyme activity by rose bengal."}
{"id": "PMID:8003", "title": "Influence of growth temperature on glucose metabolism of a psychotrophic strain of Bacillus cereus.", "content": "The influence of temperature on glucose metabolism of a psychotrophic strain of Bacillus cereus was investigated. The pH of the growth medium and spore-forming frequencies of B. cereus varied when grown at 32, 20, or 7 C. Radiorespirometric analyses revealed that vegetative cells of B. cereus metabolized glucose by simultaneous operation of the Embden-Meyerhof-Parnas pathway and the pentose phosphate pathway. As the growth temperature decreased, glucose was metabolized with increased participation of the pentose phosphate pathway. The shift of cells grown at a higher temperature to a lower temperature increased the relative participation of the pentose phosphate pathway, whereas the shift of cells grown at low temperatures to a higher temperature had the opposite effect. Cells of late logarithmic phase grown at 20 and 7 C oxidized acetate by the tricarboxylic acid cycle reaction. However, cells grown at 32 C failed to oxidize acetate to CO2 to any appreciable extent. The extracellular products resulting from the metabolism of glucose decreased as the growth temperature was lowered. Organic acids were the major extracellular products of cultures grown at 32 and 20 C. Acetic acid, lactic acid, and pyruvic acid together accounted for 86.1 and 78.9% of extracellular radioactivity, respectively, at the two temperatures. The relative ratio of these three acids varied between the temperatures. Little or no acid accumulated at 7 C.", "contents": "Influence of growth temperature on glucose metabolism of a psychotrophic strain of Bacillus cereus. The influence of temperature on glucose metabolism of a psychotrophic strain of Bacillus cereus was investigated. The pH of the growth medium and spore-forming frequencies of B. cereus varied when grown at 32, 20, or 7 C. Radiorespirometric analyses revealed that vegetative cells of B. cereus metabolized glucose by simultaneous operation of the Embden-Meyerhof-Parnas pathway and the pentose phosphate pathway. As the growth temperature decreased, glucose was metabolized with increased participation of the pentose phosphate pathway. The shift of cells grown at a higher temperature to a lower temperature increased the relative participation of the pentose phosphate pathway, whereas the shift of cells grown at low temperatures to a higher temperature had the opposite effect. Cells of late logarithmic phase grown at 20 and 7 C oxidized acetate by the tricarboxylic acid cycle reaction. However, cells grown at 32 C failed to oxidize acetate to CO2 to any appreciable extent. The extracellular products resulting from the metabolism of glucose decreased as the growth temperature was lowered. Organic acids were the major extracellular products of cultures grown at 32 and 20 C. Acetic acid, lactic acid, and pyruvic acid together accounted for 86.1 and 78.9% of extracellular radioactivity, respectively, at the two temperatures. The relative ratio of these three acids varied between the temperatures. Little or no acid accumulated at 7 C."}
{"id": "PMID:8004", "title": "Inhibition of Clostridium perfringens by heated combinations of nitrite, sulfur, and ferrous or ferric ions.", "content": "Heating mixtures of sodium nitrite, cysteine, and either ferrous sulfate or ferric chloride at 121 C for 20 min at pH 6.5 or 6.3 produced a potent inhibitor of Clostridium perfringens vegetative cells and spores when added to previously heat-sterilized fluid thioglycolate medium. When the mixtures containing FeSO4 at pH 5.2 or FeCl3 at pH 2.7 were heated, the inhibitory effect was not produced. These responses seem to eliminate the possibility that cysteine nitrosothiol is the agent responsible for the heated-nitrite inhibition known as the Perigo effect. The variable pH responses also cast doubt upon the role of the black Roussin salt as the agent of the Perigo effect.", "contents": "Inhibition of Clostridium perfringens by heated combinations of nitrite, sulfur, and ferrous or ferric ions. Heating mixtures of sodium nitrite, cysteine, and either ferrous sulfate or ferric chloride at 121 C for 20 min at pH 6.5 or 6.3 produced a potent inhibitor of Clostridium perfringens vegetative cells and spores when added to previously heat-sterilized fluid thioglycolate medium. When the mixtures containing FeSO4 at pH 5.2 or FeCl3 at pH 2.7 were heated, the inhibitory effect was not produced. These responses seem to eliminate the possibility that cysteine nitrosothiol is the agent responsible for the heated-nitrite inhibition known as the Perigo effect. The variable pH responses also cast doubt upon the role of the black Roussin salt as the agent of the Perigo effect."}
{"id": "PMID:8005", "title": "Pathways of microbial metabolism of parathion.", "content": "A mixed bacterial culture, consisting of a minimum of nine isolates, was adapted to growth on technical parathion (PAR) as a sole carbon and energy source. The primary oxidative pathway for PAR metabolism involved an initial hydrolysis to yield diethylthiophosphoric acid and p-nitrophenol. A secondary oxidative pathway involved the oxidation of PAR to paraoxon and then hydrolysis to yield p-nitrophenol and diethylphosphoric acid. Under low oxgen conditions PAR was reduced via a third pathway to p-aminoparathion and subsequently hydrolyzed to p-aminophenol and diethylthiophosphoric acid. PAR hydrolase, an enzyme produced by an isolate from the mixed culture, rapidly hydrolyzed PAR and paraoxon (6.0 mumol/mg per min). This enzyme was inducible and stable at room temperature and retained 100% of its activity when heated for 55 C for 10 min.", "contents": "Pathways of microbial metabolism of parathion. A mixed bacterial culture, consisting of a minimum of nine isolates, was adapted to growth on technical parathion (PAR) as a sole carbon and energy source. The primary oxidative pathway for PAR metabolism involved an initial hydrolysis to yield diethylthiophosphoric acid and p-nitrophenol. A secondary oxidative pathway involved the oxidation of PAR to paraoxon and then hydrolysis to yield p-nitrophenol and diethylphosphoric acid. Under low oxgen conditions PAR was reduced via a third pathway to p-aminoparathion and subsequently hydrolyzed to p-aminophenol and diethylthiophosphoric acid. PAR hydrolase, an enzyme produced by an isolate from the mixed culture, rapidly hydrolyzed PAR and paraoxon (6.0 mumol/mg per min). This enzyme was inducible and stable at room temperature and retained 100% of its activity when heated for 55 C for 10 min."}
{"id": "PMID:8006", "title": "Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans.", "content": "The microbiological oxidation of synthetic chalcocite and covellite has been investigated using an adapted strain of Thiobacillus ferrooxidans. Biodegradation of chalcocite was found to be 90 to 100% and that of covellite 45 to 60%. Optimum conditions for the oxidation of chalcocite were: pH, 1.7 to 2.3; temperature, 35 C; and ferric iron concentration in the range of 0.004 to 0.01 M. For covellite, the optimum conditions were: pH 2.3; temperature, 35 C; and ferric iron concentration in the range of 0.004 to 0.02 M. The energies of activation were determined to be 16.3 kcal (ca. 6.8 X 10(4) J) per mol and 11.7 kcal (ca. 4.8 X 10(4) J) per mol for chalcocite and covellite, respectively.", "contents": "Microbiological oxidation of synthetic chalcocite and covellite by Thiobacillus ferrooxidans. The microbiological oxidation of synthetic chalcocite and covellite has been investigated using an adapted strain of Thiobacillus ferrooxidans. Biodegradation of chalcocite was found to be 90 to 100% and that of covellite 45 to 60%. Optimum conditions for the oxidation of chalcocite were: pH, 1.7 to 2.3; temperature, 35 C; and ferric iron concentration in the range of 0.004 to 0.01 M. For covellite, the optimum conditions were: pH 2.3; temperature, 35 C; and ferric iron concentration in the range of 0.004 to 0.02 M. The energies of activation were determined to be 16.3 kcal (ca. 6.8 X 10(4) J) per mol and 11.7 kcal (ca. 4.8 X 10(4) J) per mol for chalcocite and covellite, respectively."}
{"id": "PMID:8016", "title": "Marrow transplantation in treatment of children with aplastic anaemia or acute leukaemia.", "content": "Seventy-six patients, aged 2 to 17 years, were treated with bone marrow transplantation for severe aplastic anaemia or acute leukaemia refractory to conventional therapy. 16 of the 22 patients (73%) who received marrow transplantations for aplastic anaemia are surviving, 12 of these for over one year. In acute leukaemia, using preparation with cyclophosphamide and total body irradiation, 8 of 33 patients (24%) receiving allogeneic and 5 of 8 (63%) receiving syngeneic transplantations are continuing in remission from 3 months to beyond 2 years. The longest continuing remission off therapy is now over 4 1/2 years after preparation with total body irradiation. The major causes of failure remain graft-versus-host disease, infection, graft rejection (aplastic anaemia), and leukaemic relapse.", "contents": "Marrow transplantation in treatment of children with aplastic anaemia or acute leukaemia. Seventy-six patients, aged 2 to 17 years, were treated with bone marrow transplantation for severe aplastic anaemia or acute leukaemia refractory to conventional therapy. 16 of the 22 patients (73%) who received marrow transplantations for aplastic anaemia are surviving, 12 of these for over one year. In acute leukaemia, using preparation with cyclophosphamide and total body irradiation, 8 of 33 patients (24%) receiving allogeneic and 5 of 8 (63%) receiving syngeneic transplantations are continuing in remission from 3 months to beyond 2 years. The longest continuing remission off therapy is now over 4 1/2 years after preparation with total body irradiation. The major causes of failure remain graft-versus-host disease, infection, graft rejection (aplastic anaemia), and leukaemic relapse."}
{"id": "PMID:8017", "title": "Human skin proteases. Separation and characterization of two acid proteases resembling cathepsin B1 and cathepsin D and of an inhibitor of cathepsin B1.", "content": "Two acid proteases, one hydrolysing hemoglobin and the other hydrolysing benzoyl arginine naphthyamide (BANA), were separated and partially purified from human skin buffer extract. The acid protease hydrolysing hemoglobin was purified about 190 fold by Sephadex G-100 gel filtration and DEAE-cellulose chromatography. It hydrolysed hemoglobin at pH 3.5, casein at pH 5.8 and skin protein substrate at pH 6.0. It did not markedly hydrolyse synthetic protease substrates. The molecular size of this protease was 38000. The protease was insensitive to common protease modifiers and closely resembles cathepsin D purified from other organs. The BANA-hydrolysing acid protease was purified about 760 fold by Sephadex G-100 gel filtration and affinity chromatography on organomercurial Sepharose 4B gel. It preferentially hydrolysed BAEE, BANA and BAA with an optimum at pH 5.8. The hydrolysis of BAPA, LeuNA and protein substrates was very low. This acid protease was found to be highly dependent on reducing agents, as DTT, and chelating agents, as EDTA, and was inhibited by pCMB and TLCK. The molecular size of the enzyme was 28000. This protease closely resembles cathepsin B1 purified from other organs. Human skin was also shown to contain a low activity of benzoyl arginine amide (BAA) hydrolysing acid protease with a molecular size of about 50000 and resembling cathepsin B2. Human skin contained an inhibitor with a molecular size of about 13000 against human skin cathepsin B1. This inhibitor did not inhibit trypsin, chymotrypsin or skin proteases other than cathepsin B1.", "contents": "Human skin proteases. Separation and characterization of two acid proteases resembling cathepsin B1 and cathepsin D and of an inhibitor of cathepsin B1. Two acid proteases, one hydrolysing hemoglobin and the other hydrolysing benzoyl arginine naphthyamide (BANA), were separated and partially purified from human skin buffer extract. The acid protease hydrolysing hemoglobin was purified about 190 fold by Sephadex G-100 gel filtration and DEAE-cellulose chromatography. It hydrolysed hemoglobin at pH 3.5, casein at pH 5.8 and skin protein substrate at pH 6.0. It did not markedly hydrolyse synthetic protease substrates. The molecular size of this protease was 38000. The protease was insensitive to common protease modifiers and closely resembles cathepsin D purified from other organs. The BANA-hydrolysing acid protease was purified about 760 fold by Sephadex G-100 gel filtration and affinity chromatography on organomercurial Sepharose 4B gel. It preferentially hydrolysed BAEE, BANA and BAA with an optimum at pH 5.8. The hydrolysis of BAPA, LeuNA and protein substrates was very low. This acid protease was found to be highly dependent on reducing agents, as DTT, and chelating agents, as EDTA, and was inhibited by pCMB and TLCK. The molecular size of the enzyme was 28000. This protease closely resembles cathepsin B1 purified from other organs. Human skin was also shown to contain a low activity of benzoyl arginine amide (BAA) hydrolysing acid protease with a molecular size of about 50000 and resembling cathepsin B2. Human skin contained an inhibitor with a molecular size of about 13000 against human skin cathepsin B1. This inhibitor did not inhibit trypsin, chymotrypsin or skin proteases other than cathepsin B1."}
{"id": "PMID:8021", "title": "Hypotensive action of propranolol and a new beta-blocking agent, D-32 in conscious normotensive and renal hypertensive dogs.", "content": "The hypotensive actions of dl-propranolol and a new beta-blocking agent, dl-tert-butylamino-3-(2', 3'-dimethylphenoxy)-2-propanol hydrochloride (D-32) were studied in conscious normotensive and renal hypertensive dogs, using a cross-over design. The effects were compared with that of placebo (lactose 200 mg/head, p.o.) administered in a blind fashion. A marked reduction in systolic blood pressure, from 158 +/- 2.9 to 124 +/- 2.3 (mean +/- S.E.) mm Hg, was observed at 3 hr after administration of 50 mg/kg, p.o. of D-32 in renal hypertensive dogs but not in normotensive ones. In both normotensive and renal hypertensive dogs, 10 and 50 mg/kg, p.o. of D-32 caused a marked increase in heart rate. Intravenous infusion of p-OH D-32, a main metabolite of D-32 in dogs, at a rate of 1 mg/kg per min for 5 min into renal hypertensive dogs caused a significant, long-lasting fall in blood pressure and a sustained increase in heart rate, whereas that of D-32 (1 mg/kg per min for 5 min) failed to do so. Propranolol (10 and/or 50 mg/kg, p.o.) produced no significant changes in blood pressure and heart rate in both preparations. These results indicate that D-32 causes a fall in blood pressure in conscious renal hypertensive dogs mainly by a metabolite of D-32, p-OH D-32.", "contents": "Hypotensive action of propranolol and a new beta-blocking agent, D-32 in conscious normotensive and renal hypertensive dogs. The hypotensive actions of dl-propranolol and a new beta-blocking agent, dl-tert-butylamino-3-(2', 3'-dimethylphenoxy)-2-propanol hydrochloride (D-32) were studied in conscious normotensive and renal hypertensive dogs, using a cross-over design. The effects were compared with that of placebo (lactose 200 mg/head, p.o.) administered in a blind fashion. A marked reduction in systolic blood pressure, from 158 +/- 2.9 to 124 +/- 2.3 (mean +/- S.E.) mm Hg, was observed at 3 hr after administration of 50 mg/kg, p.o. of D-32 in renal hypertensive dogs but not in normotensive ones. In both normotensive and renal hypertensive dogs, 10 and 50 mg/kg, p.o. of D-32 caused a marked increase in heart rate. Intravenous infusion of p-OH D-32, a main metabolite of D-32 in dogs, at a rate of 1 mg/kg per min for 5 min into renal hypertensive dogs caused a significant, long-lasting fall in blood pressure and a sustained increase in heart rate, whereas that of D-32 (1 mg/kg per min for 5 min) failed to do so. Propranolol (10 and/or 50 mg/kg, p.o.) produced no significant changes in blood pressure and heart rate in both preparations. These results indicate that D-32 causes a fall in blood pressure in conscious renal hypertensive dogs mainly by a metabolite of D-32, p-OH D-32."}
{"id": "PMID:8022", "title": "Inhibition by suprofen and other non-narcotic analgesic drugs of the effects of prostaglandin precursor on isolated tissues and platelets.", "content": "Contractions caused by Slow Reacting Substance C(SRS-C) and by Arachidonic Acid hydroperoxide (AAP) in the guinea-pig ileum and by AAP in the rat fundus were studied in the presence of suprofen and of 3 reference compounds. The dose-related inhibitions were not due to antagonism of prostaglandins. Other agonists of gastrointestinal smooth muscle were not or only weakly antagonized. For the study of selective inhibition of AAP-induced contractions by non-narcotic analgesics, the rat fundus is the preferred preparation. In this model suprofen had an ED50 of 1.27 x 10(-7) M (0.033 mug/ml), being 1.5, 94 and 2, 020 times more potent than indomethacin, phenybutazone and acetylsalicylic acid, respectively. Suprofen also strongly inhibited malondialdehyde formation by guinea-pig platelets incubated with arachidonic acid. The reported effects point to inhibition by suprofen of prostaglandin biosynthesis. The antagonism of AAP-induced contractions in the rat fundus is a valuable test system for inhibitors of prostaglandin biosynthesis.", "contents": "Inhibition by suprofen and other non-narcotic analgesic drugs of the effects of prostaglandin precursor on isolated tissues and platelets. Contractions caused by Slow Reacting Substance C(SRS-C) and by Arachidonic Acid hydroperoxide (AAP) in the guinea-pig ileum and by AAP in the rat fundus were studied in the presence of suprofen and of 3 reference compounds. The dose-related inhibitions were not due to antagonism of prostaglandins. Other agonists of gastrointestinal smooth muscle were not or only weakly antagonized. For the study of selective inhibition of AAP-induced contractions by non-narcotic analgesics, the rat fundus is the preferred preparation. In this model suprofen had an ED50 of 1.27 x 10(-7) M (0.033 mug/ml), being 1.5, 94 and 2, 020 times more potent than indomethacin, phenybutazone and acetylsalicylic acid, respectively. Suprofen also strongly inhibited malondialdehyde formation by guinea-pig platelets incubated with arachidonic acid. The reported effects point to inhibition by suprofen of prostaglandin biosynthesis. The antagonism of AAP-induced contractions in the rat fundus is a valuable test system for inhibitors of prostaglandin biosynthesis."}
{"id": "PMID:8018", "title": "Some natural products from two soft coals. Their removal, metal-binding and enzyme inhibitory activity.", "content": "The chemical constituents of coal have not been fully characterized in relation to the incidence of coal workers' pneumoconiosis (CWP). In this study two soft coals obtained from mines in which workers had high and low incidences of CWP were leached with aqueous base and acid to remove their acidic and basic components. The results suggest that humic substances similar to those found in soil are present in the coal samples. Further, differences in the quantity of material removed ant its metal-binding and enzyme inhibitory activity are related to disease incidence.", "contents": "Some natural products from two soft coals. Their removal, metal-binding and enzyme inhibitory activity. The chemical constituents of coal have not been fully characterized in relation to the incidence of coal workers' pneumoconiosis (CWP). In this study two soft coals obtained from mines in which workers had high and low incidences of CWP were leached with aqueous base and acid to remove their acidic and basic components. The results suggest that humic substances similar to those found in soil are present in the coal samples. Further, differences in the quantity of material removed ant its metal-binding and enzyme inhibitory activity are related to disease incidence."}
{"id": "PMID:8023", "title": "Discriminative stimulus properties of analgesic drugs: narcotic versus non-narcotic analgesics.", "content": "Using a food-reinforced two-lever operant procedure, rats (n=6) were trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o., t-60'). The administration of another narcotic analgesic (pethidine) produced a dose-related generalization with the standard fentanyl treatment; six non-narcotic analygesics (suprofen, acetylsalicylic acid, indomethacin, phenacetin, phenylbutazone, tolmetin) were found not to do so. It is concluded that the ability of drugs to produce analgesia is not a sufficient condition for the drugs to produce the narcotic cue as well.", "contents": "Discriminative stimulus properties of analgesic drugs: narcotic versus non-narcotic analgesics. Using a food-reinforced two-lever operant procedure, rats (n=6) were trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o., t-60'). The administration of another narcotic analgesic (pethidine) produced a dose-related generalization with the standard fentanyl treatment; six non-narcotic analygesics (suprofen, acetylsalicylic acid, indomethacin, phenacetin, phenylbutazone, tolmetin) were found not to do so. It is concluded that the ability of drugs to produce analgesia is not a sufficient condition for the drugs to produce the narcotic cue as well."}
{"id": "PMID:8024", "title": "Comparative doses and costs of antipsychotic medication.", "content": "It is clinically useful to have a table listing the equivalent doses of the various neuroleptics to a standard, such as chlorpromazine. This article derives such data by reviewing double-blind controlled studies that used a flexible dosage schedule of neuroleptics in treating schizophrenic patients. Each neuroleptic is then converted to 100-mg chlorpromazine equivalents. This empirically derived dosage comparability table is compared with a similar table derived from the opinions of experts. Since these comparable doses produce equivalent amounts of antipsychotic activity, the cost to provide such medication was then calculated, and a table comparing the costs of the different neuroleptics was constructed. In absolute amounts, the cost differences between drugs are small. However, for any drug, large savings accrue when the largest possible capsule or tablet to achieve the desired dose is prescribed.", "contents": "Comparative doses and costs of antipsychotic medication. It is clinically useful to have a table listing the equivalent doses of the various neuroleptics to a standard, such as chlorpromazine. This article derives such data by reviewing double-blind controlled studies that used a flexible dosage schedule of neuroleptics in treating schizophrenic patients. Each neuroleptic is then converted to 100-mg chlorpromazine equivalents. This empirically derived dosage comparability table is compared with a similar table derived from the opinions of experts. Since these comparable doses produce equivalent amounts of antipsychotic activity, the cost to provide such medication was then calculated, and a table comparing the costs of the different neuroleptics was constructed. In absolute amounts, the cost differences between drugs are small. However, for any drug, large savings accrue when the largest possible capsule or tablet to achieve the desired dose is prescribed."}
{"id": "PMID:8025", "title": "Pharmacokinetics of red blood cell phenothiazine and clinical effects. Acute dystonic reactions.", "content": "Pharmacokinetics of the phenothiazine, butaperazine, were studied in relationship to acute dystonic reactions. Dystonias appeared on falling drug concentrations, more than one half-life after plasma and red blood cell (RBC) peak butaperazine concentrations. Red blood cell butaperazine kinetics differentiated better than did plasma butaperazine levels those subjects in whom dystonias would develop from those in whom they did not. We conclude that RBC phenothiazine levels may more clearly reflect drug concentration at critical brain sites than do simple plasma drug levels. Furthermore, dystonic reactions may be the result of differential sensitivity of two or more receptor systems to receptor blockade by antischizophrenic agents.", "contents": "Pharmacokinetics of red blood cell phenothiazine and clinical effects. Acute dystonic reactions. Pharmacokinetics of the phenothiazine, butaperazine, were studied in relationship to acute dystonic reactions. Dystonias appeared on falling drug concentrations, more than one half-life after plasma and red blood cell (RBC) peak butaperazine concentrations. Red blood cell butaperazine kinetics differentiated better than did plasma butaperazine levels those subjects in whom dystonias would develop from those in whom they did not. We conclude that RBC phenothiazine levels may more clearly reflect drug concentration at critical brain sites than do simple plasma drug levels. Furthermore, dystonic reactions may be the result of differential sensitivity of two or more receptor systems to receptor blockade by antischizophrenic agents."}
{"id": "PMID:8026", "title": "Takayasu arteritis. An arteriographic-pathological correlation.", "content": "We report an aortographic-pathological correlation in a patient with Takayasu arteritis. The inflammatory activity in Takayasu arteritis gradually subsides and accordingly, the histological appearance goes through a cycle of changes, ranging from acute florid inflammation to an old scarred vessel. At gross pathological inspection, the aortic intima frequently shows longitudinal wrinkling and tree-barking indistinguishable from syphilitic aortitis. In other instances, secondary atherosclerosis totally obscures the underlying changes of aortitis. In such instances, close search at various levels of the aorta is likely to uncover persistent foci of arteritis and thereby permit identification of the pathological changes as secondary to previous aortitis.", "contents": "Takayasu arteritis. An arteriographic-pathological correlation. We report an aortographic-pathological correlation in a patient with Takayasu arteritis. The inflammatory activity in Takayasu arteritis gradually subsides and accordingly, the histological appearance goes through a cycle of changes, ranging from acute florid inflammation to an old scarred vessel. At gross pathological inspection, the aortic intima frequently shows longitudinal wrinkling and tree-barking indistinguishable from syphilitic aortitis. In other instances, secondary atherosclerosis totally obscures the underlying changes of aortitis. In such instances, close search at various levels of the aorta is likely to uncover persistent foci of arteritis and thereby permit identification of the pathological changes as secondary to previous aortitis."}
{"id": "PMID:8027", "title": "Paragangliomatosis associated with multiple endocrine adenomas.", "content": "A 19-year-old woman had multiple functioning extra-adrenal paragangliomas, a pituitary adenoma associated with acromegaly, parathyroid hyperplasia, and pigmentary abnormalities. This case differs from previously described instances of multiple endocrine adenomatosis (MEA) and has features that bridge the classic MEA type 1 and 2 syndromes and possibly Von Recklinghausen disease. The coexistence of pheochromocytoma with acromegaly is extremely rare, and the association with extra-adrenal paragangiliomas appears to be unique. Thyroid parafollicular cell proliferation could not be proved by immunohistochemical or electron microscopical studies. The large number and extensive distribution of paragangliomas, ranging from neck to pelvis, is another unique feature of this case. The concept of neurocrestopathy or of an endocrine polypeptide (APUD) cell system may offer an explanation for the interrelation of these diverse growths.", "contents": "Paragangliomatosis associated with multiple endocrine adenomas. A 19-year-old woman had multiple functioning extra-adrenal paragangliomas, a pituitary adenoma associated with acromegaly, parathyroid hyperplasia, and pigmentary abnormalities. This case differs from previously described instances of multiple endocrine adenomatosis (MEA) and has features that bridge the classic MEA type 1 and 2 syndromes and possibly Von Recklinghausen disease. The coexistence of pheochromocytoma with acromegaly is extremely rare, and the association with extra-adrenal paragangiliomas appears to be unique. Thyroid parafollicular cell proliferation could not be proved by immunohistochemical or electron microscopical studies. The large number and extensive distribution of paragangliomas, ranging from neck to pelvis, is another unique feature of this case. The concept of neurocrestopathy or of an endocrine polypeptide (APUD) cell system may offer an explanation for the interrelation of these diverse growths."}
{"id": "PMID:8028", "title": "A case of pneumococcal typhlitis.", "content": "A 29-year-old man had abdominal pain for 24 hours. This and the results of an abdominal examination were typical of acute appendicitis. He had suffered sinusitis for two weeks. At operation, the appendix was normal; there was an abscess in the cecal wall, the exudate of which grew pneumococci. Incidental appendectomy was done and the patient was treated successfully with lincomycin hydrochloride, and later, cephalexin monohydrate. It is possible that the typhlitis was secondary to the upper respiratory infection.", "contents": "A case of pneumococcal typhlitis. A 29-year-old man had abdominal pain for 24 hours. This and the results of an abdominal examination were typical of acute appendicitis. He had suffered sinusitis for two weeks. At operation, the appendix was normal; there was an abscess in the cecal wall, the exudate of which grew pneumococci. Incidental appendectomy was done and the patient was treated successfully with lincomycin hydrochloride, and later, cephalexin monohydrate. It is possible that the typhlitis was secondary to the upper respiratory infection."}
{"id": "PMID:8032", "title": "Analgesic nephropathy.", "content": "Analgesic nephropathy occurs most commonly in Australia, where it is the second most frequent cause of renal failure. Whilst the reasons for widespread abuse of analgesics are poorly understood, the consequences of abuse are now well recognised. Increasing emphasis is being placed on the analgesic syndrome and on the accelerated atherosclerosis seen in these patients. Attention in the article is drawn to ways in which the analgesic syndrome can be recognised and analgesic abuse ceased. A therapeutic approach is presented which allows the successful withdrawal of analgesic in almost all patients.", "contents": "Analgesic nephropathy. Analgesic nephropathy occurs most commonly in Australia, where it is the second most frequent cause of renal failure. Whilst the reasons for widespread abuse of analgesics are poorly understood, the consequences of abuse are now well recognised. Increasing emphasis is being placed on the analgesic syndrome and on the accelerated atherosclerosis seen in these patients. Attention in the article is drawn to ways in which the analgesic syndrome can be recognised and analgesic abuse ceased. A therapeutic approach is presented which allows the successful withdrawal of analgesic in almost all patients."}
{"id": "PMID:8034", "title": "A study of the surface pH of the urinary bladder during distension in rabbits.", "content": "Bladder wall surface pH has been continuously monitored with a glass pH electrode using a simple, atraumatic technique. Experiments have been performed in the rabbit showing that there is a progressive fall in bladder wall pH as the intravesical pressure is increased. The changes in bladder wall pH serve as a sensitive indicator of bladder blood flow and so this simple method is used to assess the changes in bladder blood flow during distension.", "contents": "A study of the surface pH of the urinary bladder during distension in rabbits. Bladder wall surface pH has been continuously monitored with a glass pH electrode using a simple, atraumatic technique. Experiments have been performed in the rabbit showing that there is a progressive fall in bladder wall pH as the intravesical pressure is increased. The changes in bladder wall pH serve as a sensitive indicator of bladder blood flow and so this simple method is used to assess the changes in bladder blood flow during distension."}
{"id": "PMID:8035", "title": "The purification and properties of the glutamine synthetase from the cytosol of Soya-bean root nodules.", "content": "The major portion of glutamine synthetase activity in root nodules of soya-bean plants is associated with the cytosol rather than with Rhizobium japonicum bacteroids. Glutamine synthetase accounts for about 2% of the total soluble protein in nodule cytosol. Glutamine synthetase from nodule cytosol has been purified by a procedure involving fractionation with protamine sulphate, ammonium sulphate and polypropylene glycol, chromatography on DEAE-Bio-Gel A and Bio-Gel A-5m and affinity chromatography on glutamate-agarose columns. The purified preparation appeared to be homogeneous in the analytical ultracentrifuge. From sedimentation-equilibrium experiments a mol. wt. of about 376000 was determined for the native enzyme and 47300 for the enzyme in guanidinium chloride. From these data and measurements of electron micrographs, we have concluded that glutamine synthetase from nodule cytosol consists of eight subunits arranged in two sets of planar tetramers which form a cubical configuration with dimensions of about 10 nm (100 A) across each side. Glutamine synthetase from nodule cytosol has a higher glycine and proline content and a lower content of phenylalanine than the glutamine synthetase that has been prepared from pea seed. The cytosol enzyme contains four half-cystine molecules per subunit, which is in contrast with two reported for the enzyme from pea seed. Enzyme activity is striking influenced by the relative proportion of Mg2+ and Mn2+ in the assay medium. Activity is inhibited by feedback inhibitors and is influenced by energy charge.", "contents": "The purification and properties of the glutamine synthetase from the cytosol of Soya-bean root nodules. The major portion of glutamine synthetase activity in root nodules of soya-bean plants is associated with the cytosol rather than with Rhizobium japonicum bacteroids. Glutamine synthetase accounts for about 2% of the total soluble protein in nodule cytosol. Glutamine synthetase from nodule cytosol has been purified by a procedure involving fractionation with protamine sulphate, ammonium sulphate and polypropylene glycol, chromatography on DEAE-Bio-Gel A and Bio-Gel A-5m and affinity chromatography on glutamate-agarose columns. The purified preparation appeared to be homogeneous in the analytical ultracentrifuge. From sedimentation-equilibrium experiments a mol. wt. of about 376000 was determined for the native enzyme and 47300 for the enzyme in guanidinium chloride. From these data and measurements of electron micrographs, we have concluded that glutamine synthetase from nodule cytosol consists of eight subunits arranged in two sets of planar tetramers which form a cubical configuration with dimensions of about 10 nm (100 A) across each side. Glutamine synthetase from nodule cytosol has a higher glycine and proline content and a lower content of phenylalanine than the glutamine synthetase that has been prepared from pea seed. The cytosol enzyme contains four half-cystine molecules per subunit, which is in contrast with two reported for the enzyme from pea seed. Enzyme activity is striking influenced by the relative proportion of Mg2+ and Mn2+ in the assay medium. Activity is inhibited by feedback inhibitors and is influenced by energy charge."}
{"id": "PMID:8036", "title": "Activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenase in muscle from vertebrates and invertebrates.", "content": "1. The activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were measured in muscles from a large number of animals, in order to provide some indication of the importance of the citric acid cycle in these muscles. According to the differences in enzyme activities, the muscles can be divided into three classes. First, in a number of both vertebrate and invertebrate muscles, the activities of all three enzymes are very low. It is suggested that either the muscles use energy at a very low rate or they rely largely on anaerobic glycolysis for higher rates of energy formation. Second, most insect flight muscles contain high activities of citrate synthase and NAD+-linked isocitrate dehydrogenase, but the activities of the NADP+-linked enzyme are very low. The high activities indicate the dependence of insect flight on energy generated via the citric acid cycle. The flight muscles of the beetles investigated contain high activities of both isocitrate dehydrogenases. Third, other muscles of both vertebrates and invertebrates contain high activities of citrate synthase and NADP+-liniked isocitrate dehydrogenase. Many, if not all, of these muscles are capable of sustained periods of mechanical activity (e.g. heart muscle, pectoral muscles of some birds). Consequently, to support this activity fuel must be supplied continually to the muscle via the circulatory system which, in most animals, also transports oxygen so that energy can be generated by complete oxidation of the fuel. It is suggested that the low activities of NAD+-linked isocitrate dehydrogenase in these muscles may be involved in oxidation of isocitrate in the cycle when the muscles are at rest. 2. A comparison of the maximal activities of the enzymes with the maximal flux through the cycle suggests that, in insect flight muscle, NAD+-linked isocitrate dehydrogenase catalyses a non-equilibrium reaction and citrate synthease catalyses a near-equilibrium reaction. In other muscles, the enzyme-activity data suggest that both citrate synthase and the isocitrate dehydrogenase reactions are near-equilibrium.", "contents": "Activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenase in muscle from vertebrates and invertebrates. 1. The activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were measured in muscles from a large number of animals, in order to provide some indication of the importance of the citric acid cycle in these muscles. According to the differences in enzyme activities, the muscles can be divided into three classes. First, in a number of both vertebrate and invertebrate muscles, the activities of all three enzymes are very low. It is suggested that either the muscles use energy at a very low rate or they rely largely on anaerobic glycolysis for higher rates of energy formation. Second, most insect flight muscles contain high activities of citrate synthase and NAD+-linked isocitrate dehydrogenase, but the activities of the NADP+-linked enzyme are very low. The high activities indicate the dependence of insect flight on energy generated via the citric acid cycle. The flight muscles of the beetles investigated contain high activities of both isocitrate dehydrogenases. Third, other muscles of both vertebrates and invertebrates contain high activities of citrate synthase and NADP+-liniked isocitrate dehydrogenase. Many, if not all, of these muscles are capable of sustained periods of mechanical activity (e.g. heart muscle, pectoral muscles of some birds). Consequently, to support this activity fuel must be supplied continually to the muscle via the circulatory system which, in most animals, also transports oxygen so that energy can be generated by complete oxidation of the fuel. It is suggested that the low activities of NAD+-linked isocitrate dehydrogenase in these muscles may be involved in oxidation of isocitrate in the cycle when the muscles are at rest. 2. A comparison of the maximal activities of the enzymes with the maximal flux through the cycle suggests that, in insect flight muscle, NAD+-linked isocitrate dehydrogenase catalyses a non-equilibrium reaction and citrate synthease catalyses a near-equilibrium reaction. In other muscles, the enzyme-activity data suggest that both citrate synthase and the isocitrate dehydrogenase reactions are near-equilibrium."}
{"id": "PMID:8037", "title": "Autophagy-related changes of arylsulphatases A and B in rat liver lysosomes.", "content": "The total arylsulphatase activity and the relative activities of lysosomal arylsulphatases A and B were measured in the liver of control rats and rats subjected to treatments that provoke hepatic autophagocytosis. The total liver arylsulphatase activities were increased in starved and starved glucagon-treated rats, but not in sham-operated and hepatectomized rats. Arylsulphatases A and B in the mitochondrial-lysosomal (M-L) fraction were separated by polyacrylamide-gel electrophoresis at pH 8.8; they were made visible by incubating the gels with p-nitrocatechol sulphate as substrate, and measured by quantitative densitometry. In untreated controls, arylsulphatases A and B comprised 41.4 +/- 0.5% and 58.6 +/- 0.5% of the total arylsulphatase activity respectively; the arylsulphatase A/arylsulphatase B activity ratio was 0.71. All experimental treatments produced a significant decrease in the percentage of lysosomal arylsulphatase present as the A form and an increase in that present as the B form, and the activity ratio of arylsulphatase A/arylsulphatase B declined. The magnitude of these changes increased in the following direction: starvation for 24h=sham hepatectomy less than glucagon + starvation less than subtotal hepatectomy. These results indicate that the arylsulphatase A/arylsulphatase B activity ratio in liver lysosomes of normal rats is maintained within rather narrow limits, and this ratio declines during enhanced autophagocytosis. These findings, together with observations that suggest that arylsulphatase B may be a partially degraded form of arylsulphatase A, are consistent with the view that the A form is more rapidly converted into the B form during autophagy, owing to the digestive activity of the other lysosomal hydrolases present in autophagic vacuoles.", "contents": "Autophagy-related changes of arylsulphatases A and B in rat liver lysosomes. The total arylsulphatase activity and the relative activities of lysosomal arylsulphatases A and B were measured in the liver of control rats and rats subjected to treatments that provoke hepatic autophagocytosis. The total liver arylsulphatase activities were increased in starved and starved glucagon-treated rats, but not in sham-operated and hepatectomized rats. Arylsulphatases A and B in the mitochondrial-lysosomal (M-L) fraction were separated by polyacrylamide-gel electrophoresis at pH 8.8; they were made visible by incubating the gels with p-nitrocatechol sulphate as substrate, and measured by quantitative densitometry. In untreated controls, arylsulphatases A and B comprised 41.4 +/- 0.5% and 58.6 +/- 0.5% of the total arylsulphatase activity respectively; the arylsulphatase A/arylsulphatase B activity ratio was 0.71. All experimental treatments produced a significant decrease in the percentage of lysosomal arylsulphatase present as the A form and an increase in that present as the B form, and the activity ratio of arylsulphatase A/arylsulphatase B declined. The magnitude of these changes increased in the following direction: starvation for 24h=sham hepatectomy less than glucagon + starvation less than subtotal hepatectomy. These results indicate that the arylsulphatase A/arylsulphatase B activity ratio in liver lysosomes of normal rats is maintained within rather narrow limits, and this ratio declines during enhanced autophagocytosis. These findings, together with observations that suggest that arylsulphatase B may be a partially degraded form of arylsulphatase A, are consistent with the view that the A form is more rapidly converted into the B form during autophagy, owing to the digestive activity of the other lysosomal hydrolases present in autophagic vacuoles."}
{"id": "PMID:8038", "title": "Hydrogen-ion titration studies on erythrocyte membranes.", "content": "1. H+ titration was used to detect the presence of ionizable groups on human erythrocyte plasma membranes. Between pH2.9 and 11.3, two significant peaks of H+ association/dissociation occur in the differential from of the titration curve, one at pH3. 1. And the other at pH10.3. 2. After disruption of membrane structure by exposure to high pH or by the addition of sodium dodecyl sulphate, maxima of H+ association/dissociation were seen at pH3.1,4.3,6.5,10.3  and 10.7. 3. Spectrophotometric assay and selective chemical treatments were used to identify several of the titratable residues. 4. The degree of eleectrostatic interaction between titratable charged groups was investigated by comparing the titration characteristics of the membranes before and after modification of membrane structure.", "contents": "Hydrogen-ion titration studies on erythrocyte membranes. 1. H+ titration was used to detect the presence of ionizable groups on human erythrocyte plasma membranes. Between pH2.9 and 11.3, two significant peaks of H+ association/dissociation occur in the differential from of the titration curve, one at pH3. 1. And the other at pH10.3. 2. After disruption of membrane structure by exposure to high pH or by the addition of sodium dodecyl sulphate, maxima of H+ association/dissociation were seen at pH3.1,4.3,6.5,10.3  and 10.7. 3. Spectrophotometric assay and selective chemical treatments were used to identify several of the titratable residues. 4. The degree of eleectrostatic interaction between titratable charged groups was investigated by comparing the titration characteristics of the membranes before and after modification of membrane structure."}
{"id": "PMID:8039", "title": "The route of secretion of procollagen. The influence of alphaalpha'-bipyridyl, colchicine and antimycin A on the secretory process in embryonic-chick tendon and cartilage cells.", "content": "I. Embryonic-chick tendon cells were pulse-labelled for 4 min with [14C]proline and the 14C-labelled polypeptides were chased with unlabelled proline for up to 30 min. Isolation of subcellular fractions during the chase period and their subsequent analysis for bacterial collagenase-susceptible 14C-labelled peptides demonstrated the transfer of procollagen polypeptides from rough to smooth microsomal fractions and thence to the extracellular medium. Parallel analyses of Golgi-enriched fractions indicated the involvement of this organelle in the secretory pathway of procollagen. Sodium dodecylsulphate/polyacrylamide-gel electrophoresis of the 14C-labelled polypeptides present in the Golgi-enriched fractions demonstrated that the procollagen polypeptides were all present as disulphide-linked pro-gamma components. 2. When similar kinetic studies of the intracellular transport of procollagen were conducted with embryonic-chick cartilage cells almost identical results were obtained, but the rate of translocation of cartilage procollagen was significantly slower than that observed for tendon procollagen. 3. When hydroxylation of procollagen polypeptides was inhibited by alphaalpha'-bipyridyl, the nascent polypeptides accumulated in the rough microsomal fraction. 4. When cells were pulse-labelled for 4min with [14C)proline and the label was chased in the presence of colchicine, secretion of procollagen was inhibited and an intracellular accumulation of procollagen 14C-labelled polypeptides was observed in the Golgi-enriched fractions. 5. The energy-dependence of the intracellular transport of procollagen was demonstrated in experiments in which antimycin A was found to inhibit the transfer of procollagen polypeptides from rough to smooth endoplasmic reticulum. 6. It is concluded that procollagen follows the classical route of secretion taken by other extracellular proteins.", "contents": "The route of secretion of procollagen. The influence of alphaalpha'-bipyridyl, colchicine and antimycin A on the secretory process in embryonic-chick tendon and cartilage cells. I. Embryonic-chick tendon cells were pulse-labelled for 4 min with [14C]proline and the 14C-labelled polypeptides were chased with unlabelled proline for up to 30 min. Isolation of subcellular fractions during the chase period and their subsequent analysis for bacterial collagenase-susceptible 14C-labelled peptides demonstrated the transfer of procollagen polypeptides from rough to smooth microsomal fractions and thence to the extracellular medium. Parallel analyses of Golgi-enriched fractions indicated the involvement of this organelle in the secretory pathway of procollagen. Sodium dodecylsulphate/polyacrylamide-gel electrophoresis of the 14C-labelled polypeptides present in the Golgi-enriched fractions demonstrated that the procollagen polypeptides were all present as disulphide-linked pro-gamma components. 2. When similar kinetic studies of the intracellular transport of procollagen were conducted with embryonic-chick cartilage cells almost identical results were obtained, but the rate of translocation of cartilage procollagen was significantly slower than that observed for tendon procollagen. 3. When hydroxylation of procollagen polypeptides was inhibited by alphaalpha'-bipyridyl, the nascent polypeptides accumulated in the rough microsomal fraction. 4. When cells were pulse-labelled for 4min with [14C)proline and the label was chased in the presence of colchicine, secretion of procollagen was inhibited and an intracellular accumulation of procollagen 14C-labelled polypeptides was observed in the Golgi-enriched fractions. 5. The energy-dependence of the intracellular transport of procollagen was demonstrated in experiments in which antimycin A was found to inhibit the transfer of procollagen polypeptides from rough to smooth endoplasmic reticulum. 6. It is concluded that procollagen follows the classical route of secretion taken by other extracellular proteins."}
{"id": "PMID:8040", "title": "The effects of proteolytic digestion by trypsin on the structure and catalytic properties of reduced nicotinamide-adenine dinucleotide dehydrogenase from bovine heart mitochondria.", "content": "1. At 21 degrees C incubation of NADH-ubiquinone-1 reductase (Complex 1) with trypsin caused selective inhibition of nicotinamide nucleotide transhydrogenase activity. The reduction of K3Fe(CN)6 by NADH or NADPH was unaffected, but a slow decrease in the rate of reduction of ubiquinone-1 by NADH was observed. 2. The pH-dependence of nicotinamide nucleotide transhydrogenase activity differed in Complex I and trypsin-treated Complex I. The trypsin-labile activity had a pH optimum of approx. 6.5, whereas the trypsin-resistant activity had a pH optimum of approx. 5.5 or less. 3. The trypsinlabile transhydrogenase activity was specifically inhibited by butanedione or phenylglyoxal and was identified with the enzyme catalysing energy-linked transhydrogenase activity in submitochondrial particles. 4. Polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate revealed that trypsin caused degradation of a polypeptide of mol.wt 20500 in parallel with the loss of transhydrogenase activity. 5. At 30 degrees C and higher trypsin concentrations, the rate of reduction of K3Fe(CN)6 by NADH or NADPH slowly decreased. Increased lability of NADH-K3Fe(CN)6 reductase activity to trypsin was observed when the endogenous phospholipid of Complex I was depleted by detergent or phospholipase A treatment. 6. Polyacrylamide-gel electrophoresis indicated that removal of phospholipid allowed much more extensive degradation of constituent polypeptides by trypsin. The subunits of the low-molecular-weight (type II) dehydrogenase (53000 and 26000 mol.wt.) were, however, relatively resistant to trypsin even in phospholipid-depleted preparations.", "contents": "The effects of proteolytic digestion by trypsin on the structure and catalytic properties of reduced nicotinamide-adenine dinucleotide dehydrogenase from bovine heart mitochondria. 1. At 21 degrees C incubation of NADH-ubiquinone-1 reductase (Complex 1) with trypsin caused selective inhibition of nicotinamide nucleotide transhydrogenase activity. The reduction of K3Fe(CN)6 by NADH or NADPH was unaffected, but a slow decrease in the rate of reduction of ubiquinone-1 by NADH was observed. 2. The pH-dependence of nicotinamide nucleotide transhydrogenase activity differed in Complex I and trypsin-treated Complex I. The trypsin-labile activity had a pH optimum of approx. 6.5, whereas the trypsin-resistant activity had a pH optimum of approx. 5.5 or less. 3. The trypsinlabile transhydrogenase activity was specifically inhibited by butanedione or phenylglyoxal and was identified with the enzyme catalysing energy-linked transhydrogenase activity in submitochondrial particles. 4. Polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate revealed that trypsin caused degradation of a polypeptide of mol.wt 20500 in parallel with the loss of transhydrogenase activity. 5. At 30 degrees C and higher trypsin concentrations, the rate of reduction of K3Fe(CN)6 by NADH or NADPH slowly decreased. Increased lability of NADH-K3Fe(CN)6 reductase activity to trypsin was observed when the endogenous phospholipid of Complex I was depleted by detergent or phospholipase A treatment. 6. Polyacrylamide-gel electrophoresis indicated that removal of phospholipid allowed much more extensive degradation of constituent polypeptides by trypsin. The subunits of the low-molecular-weight (type II) dehydrogenase (53000 and 26000 mol.wt.) were, however, relatively resistant to trypsin even in phospholipid-depleted preparations."}
{"id": "PMID:8041", "title": "The regulation of rat liver tryptophan pyrrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Experiments with glucose and nicotinamide.", "content": "1. Chronic administration of glucose or nicotinamide in drinking water inhibits the activity of rat liver tryptophan pyrrolase, and subsequent withdrawal causes an enhancement. The enzyme activity is also inhibited by administration in drinking water of sucrose, but not fructose, which is capable of preventing the glucose effect. 2. The inhibition by glucose or nictinamide is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. 3. The inhibition by nicotinamide is reversed by regeneration of liver NAD+ and NADP+ in vivo by administration of fructose, pyruvate or phenazine methosulphate. Inhibition by glucose is also reversed by the above agents and by NH4Cl. Reversal of inhibition by glucose or nicotinamide is also achieved in vitro by addition of NAD+ or NADP+. 4. Glucose or nicotinamide increases liver [NADPH]. [NADP+] is also increased by nicotinamide. [NADPH] is also increased by sucrose, but not by fructose, which prevents the glucose effect. Phenazine methosulphate prevents the increase in [NADPH] caused by both glucose and nicotinamide. 5. It is suggested that the inhibition of tryptophan pyrrolase activity by glucose or nicotinamide is mediated by both NADPH and NADH.", "contents": "The regulation of rat liver tryptophan pyrrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Experiments with glucose and nicotinamide. 1. Chronic administration of glucose or nicotinamide in drinking water inhibits the activity of rat liver tryptophan pyrrolase, and subsequent withdrawal causes an enhancement. The enzyme activity is also inhibited by administration in drinking water of sucrose, but not fructose, which is capable of preventing the glucose effect. 2. The inhibition by glucose or nictinamide is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. 3. The inhibition by nicotinamide is reversed by regeneration of liver NAD+ and NADP+ in vivo by administration of fructose, pyruvate or phenazine methosulphate. Inhibition by glucose is also reversed by the above agents and by NH4Cl. Reversal of inhibition by glucose or nicotinamide is also achieved in vitro by addition of NAD+ or NADP+. 4. Glucose or nicotinamide increases liver [NADPH]. [NADP+] is also increased by nicotinamide. [NADPH] is also increased by sucrose, but not by fructose, which prevents the glucose effect. Phenazine methosulphate prevents the increase in [NADPH] caused by both glucose and nicotinamide. 5. It is suggested that the inhibition of tryptophan pyrrolase activity by glucose or nicotinamide is mediated by both NADPH and NADH."}
{"id": "PMID:8056", "title": "Basic ethers of cyclohexylphenols with beta-blocking activity: synthesis and pharmacological study of exaprolol.", "content": "The paper describes the preparation and study of the pharmacological properties of a series of derivatives with the general formula. (see article) where R is a cyclohexyl or cyclohexenyl radical and R1 is a hydrogen, methyl or cyclohexyl. The compounds with a single cycloaliphatic radical ortho to the basic chain, and in particular the one with a cyclohexyl (exaprolol), were found to be particularly active in blocking the beta-adrenergic receptors, as antiarrhythmics and local anesthetics, while the introduction of a second radical or the shift of the cycloaliphatic radical to meta or para position caused the said pharmacological activities to disappear almost entirely, with the exception of the local anesthetic action.", "contents": "Basic ethers of cyclohexylphenols with beta-blocking activity: synthesis and pharmacological study of exaprolol. The paper describes the preparation and study of the pharmacological properties of a series of derivatives with the general formula. (see article) where R is a cyclohexyl or cyclohexenyl radical and R1 is a hydrogen, methyl or cyclohexyl. The compounds with a single cycloaliphatic radical ortho to the basic chain, and in particular the one with a cyclohexyl (exaprolol), were found to be particularly active in blocking the beta-adrenergic receptors, as antiarrhythmics and local anesthetics, while the introduction of a second radical or the shift of the cycloaliphatic radical to meta or para position caused the said pharmacological activities to disappear almost entirely, with the exception of the local anesthetic action."}
{"id": "PMID:8057", "title": "General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity.", "content": "1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses.", "contents": "General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity. 1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses."}
{"id": "PMID:8058", "title": "[Bronchospasmolytic activity of aqueous aerosols in anesthetized dogs (author's transl)].", "content": "A modification of the method of Konzett and R\u00f6ssler is described. This modification allows the administration of atomised drug solutions to anaesthetised dogs. Information is thus obtained on the bronchodilatory activity of a drug and the onset and duration of effect. Two anticholinergics (atropinsulfate and ipratropiumbromide) and three beta-adrenoceptor stimulants (isoprenaline, orciprenaline and salbutamol) were investigated. After local administration as aerosols the anticholinergics proved to be as potent or even more so than the beta-adrenoceptor stimulants.", "contents": "[Bronchospasmolytic activity of aqueous aerosols in anesthetized dogs (author's transl)]. A modification of the method of Konzett and R\u00f6ssler is described. This modification allows the administration of atomised drug solutions to anaesthetised dogs. Information is thus obtained on the bronchodilatory activity of a drug and the onset and duration of effect. Two anticholinergics (atropinsulfate and ipratropiumbromide) and three beta-adrenoceptor stimulants (isoprenaline, orciprenaline and salbutamol) were investigated. After local administration as aerosols the anticholinergics proved to be as potent or even more so than the beta-adrenoceptor stimulants."}
{"id": "PMID:8059", "title": "Actions of narcotics on brain dopamine metabolism and their relevance for \"psychomotor\" effects.", "content": "A review is given about the effects of narcotic analgesics, particularly of morphine, on the dopamine metabolism in the corpus striatum and about the relations of these effects to motility and \"psychomotor\" phenomena. In rats, acute doses of morphine decrease the dopaminergic neurotransmission in brain, without blocking postsynaptic dopamine receptors. Chronic treatment of rats with morphine reverses these acute effects of morphine and induces symptoms of an increased dopaminergic neurotransmission in brain. In mice and cats on the other hand, acute doses of morphine apparently increase dopaminergic neurotransmission. The effects of morphine on striatal dopamine metabolism seem to be a model well suited to study opioid-specific effects on a cellular level. Furthermore, they might also be responsible for some narcotic-specific effects on behaviour observed in animals and man.", "contents": "Actions of narcotics on brain dopamine metabolism and their relevance for \"psychomotor\" effects. A review is given about the effects of narcotic analgesics, particularly of morphine, on the dopamine metabolism in the corpus striatum and about the relations of these effects to motility and \"psychomotor\" phenomena. In rats, acute doses of morphine decrease the dopaminergic neurotransmission in brain, without blocking postsynaptic dopamine receptors. Chronic treatment of rats with morphine reverses these acute effects of morphine and induces symptoms of an increased dopaminergic neurotransmission in brain. In mice and cats on the other hand, acute doses of morphine apparently increase dopaminergic neurotransmission. The effects of morphine on striatal dopamine metabolism seem to be a model well suited to study opioid-specific effects on a cellular level. Furthermore, they might also be responsible for some narcotic-specific effects on behaviour observed in animals and man."}
{"id": "PMID:8060", "title": "Metabolic deacetylation: in vitro and in vivo studies in man, rat, dog and rhesus monkey with isomeric tetrahydroisoquinolyl derivatives of 3,4-dimethylbenzyl acetate.", "content": "The pharmacological activities of a racemic mixture of tetrahydroisoquinolyl derivatives of 3,4-dimethylbenzyl acetate, (+/-) Ro 03-4661 and the corresponding resolved isomers (+) Ro 03-4661 and (--) Ro 03-4661 have been studied in rat and rhesus monkey. The racemate and the (--) isomer showed narcotic analgesic activity by the oral route in both species. Drug metabolism studies indicated that the activity was probably due to metabolic Deacetylation to the corresponding carbinol Ro 03-4632. deacetylation did not occur in the dog, but was observed in the rat and rhesus monkey. In both these species the hydrolysis was more extensive after oral than parenteral administration. In vitro studies also showed considerable species variation in the ability of blood and tissue esterases to hydrolyse the different stereochemical isomers.", "contents": "Metabolic deacetylation: in vitro and in vivo studies in man, rat, dog and rhesus monkey with isomeric tetrahydroisoquinolyl derivatives of 3,4-dimethylbenzyl acetate. The pharmacological activities of a racemic mixture of tetrahydroisoquinolyl derivatives of 3,4-dimethylbenzyl acetate, (+/-) Ro 03-4661 and the corresponding resolved isomers (+) Ro 03-4661 and (--) Ro 03-4661 have been studied in rat and rhesus monkey. The racemate and the (--) isomer showed narcotic analgesic activity by the oral route in both species. Drug metabolism studies indicated that the activity was probably due to metabolic Deacetylation to the corresponding carbinol Ro 03-4632. deacetylation did not occur in the dog, but was observed in the rat and rhesus monkey. In both these species the hydrolysis was more extensive after oral than parenteral administration. In vitro studies also showed considerable species variation in the ability of blood and tissue esterases to hydrolyse the different stereochemical isomers."}
{"id": "PMID:8061", "title": "Purification and characterization of lipoprotein lipase from human heart.", "content": "Human heart lipoprotein lipase was purified by affinity chromatography on heparin-Sepharose 4B. When crude extracts of heart acetone powder were applied to columsn, about 40% of total lipase activity was bound to the gel and then eluted with 1.5 M NaCl. At this stage the eluted enzyme was purified 1900-fold. Disc gel electrophoresis yielded a single protein band corresponding with lipolytic activity. Minimum molecular weight of the protein was 60,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme was highly unstable; however, its activity could be partially stabilized at --20C by bovine serum albumin, glycerol, or ethylene glycol. The activity of the purified enzyme (i) had a pH optimum between 7.8 and 8.0; (ii) required serum for full enzymatic activity; apoC-II could be substituted for serum; (iii) was inhibited by by apoC-I in the presence of activated substrate; (iv) was markedly inhibited by NaCl; and (v) was stimulated by heparin.", "contents": "Purification and characterization of lipoprotein lipase from human heart. Human heart lipoprotein lipase was purified by affinity chromatography on heparin-Sepharose 4B. When crude extracts of heart acetone powder were applied to columsn, about 40% of total lipase activity was bound to the gel and then eluted with 1.5 M NaCl. At this stage the eluted enzyme was purified 1900-fold. Disc gel electrophoresis yielded a single protein band corresponding with lipolytic activity. Minimum molecular weight of the protein was 60,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme was highly unstable; however, its activity could be partially stabilized at --20C by bovine serum albumin, glycerol, or ethylene glycol. The activity of the purified enzyme (i) had a pH optimum between 7.8 and 8.0; (ii) required serum for full enzymatic activity; apoC-II could be substituted for serum; (iii) was inhibited by by apoC-I in the presence of activated substrate; (iv) was markedly inhibited by NaCl; and (v) was stimulated by heparin."}
{"id": "PMID:8062", "title": "Neurogenic hypercholesterolemia: influence of autonomic drugs.", "content": "Eleven substances capable of either augmenting or depleting the alpha- and - beta-adrenergic capacities of the autonomic nervous system were administered to rats exhibiting hypothalamic hypercholesterolemia and to normal controls. Only the beta-adrenergic blocking agents propranolol and possibly 6-OH dopamine were observed to alter (raise) the serum cholesterol concentration, and this occurred in both experimental and control animals. Neither atropine, nor the serotonin-depleting agent, rho-chlorophenylalanine, nor the serotonin-antagonist cyproheptadine, were observed to alter serum cholesterol level. Such absence of effect was also noted with metaraminol, phenoxybenzamine, isoproterenol, epinephrine, reserpine, and alpha-methyl tyrosine.", "contents": "Neurogenic hypercholesterolemia: influence of autonomic drugs. Eleven substances capable of either augmenting or depleting the alpha- and - beta-adrenergic capacities of the autonomic nervous system were administered to rats exhibiting hypothalamic hypercholesterolemia and to normal controls. Only the beta-adrenergic blocking agents propranolol and possibly 6-OH dopamine were observed to alter (raise) the serum cholesterol concentration, and this occurred in both experimental and control animals. Neither atropine, nor the serotonin-depleting agent, rho-chlorophenylalanine, nor the serotonin-antagonist cyproheptadine, were observed to alter serum cholesterol level. Such absence of effect was also noted with metaraminol, phenoxybenzamine, isoproterenol, epinephrine, reserpine, and alpha-methyl tyrosine."}
{"id": "PMID:8063", "title": "Effects of some benzodiazepine derivatives on Triton WR-1339-Induced hyperlipidaemia in rats.", "content": "Oral administration of the benzodiazepines (diazepam, lorazepam, chlordiazepoxide, bipotassium chlorazepate) in Triton WR-1339-induced (200 mg/kg, blood collection 18 h later) hyperlipidaemia in rats elicited marked decrease of serum total lipids, total cholesterol and triglyceride levels, and alterations in free fatty acid and free glycerol content. The optimal doses for diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were estimated to be 5 mg/kg. Other benzodiazepines, namely oxazepam, medazepam and nitrazepam, elicited only minor changes in serum lipids levels, while with grandaxin no change was observed. The optimal doses of diazepam and lorazepam brought about the same changes in serum lipid content as did clofibrate (90 mg/kg, p. o.). If diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were administered in doses of 5 mg/kg in Triton WR-1339-treated rats (blood collection taken 3 h later), a significant decrease of total lipids and triglyceride levels was observed. The free glycerol level only altered after the administration of chlordiazepoxide, which brought about a significant reduction.", "contents": "Effects of some benzodiazepine derivatives on Triton WR-1339-Induced hyperlipidaemia in rats. Oral administration of the benzodiazepines (diazepam, lorazepam, chlordiazepoxide, bipotassium chlorazepate) in Triton WR-1339-induced (200 mg/kg, blood collection 18 h later) hyperlipidaemia in rats elicited marked decrease of serum total lipids, total cholesterol and triglyceride levels, and alterations in free fatty acid and free glycerol content. The optimal doses for diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were estimated to be 5 mg/kg. Other benzodiazepines, namely oxazepam, medazepam and nitrazepam, elicited only minor changes in serum lipids levels, while with grandaxin no change was observed. The optimal doses of diazepam and lorazepam brought about the same changes in serum lipid content as did clofibrate (90 mg/kg, p. o.). If diazepam, lorazepam, chlordiazepoxide and bipotassium chlorazepate were administered in doses of 5 mg/kg in Triton WR-1339-treated rats (blood collection taken 3 h later), a significant decrease of total lipids and triglyceride levels was observed. The free glycerol level only altered after the administration of chlordiazepoxide, which brought about a significant reduction."}
{"id": "PMID:8068", "title": "Clinical studies of induction agents XLIII: Flunitrazepam.", "content": "Flunitrazepam (Ro 5-4200) has been studied as an induction agent in 220 volunteers or patients. It was assumed to be 10 times as potent as diazepam. The maximum soporific effect did not occur until 90-120 s after injection. There was great individual variation in response to flunitrazepam and some patients did not lose consciousness even after receiving 6 mg (approximately 0.1 mg/kg). Opiate premedication enhanced its action, but delayed recovery. There was a dose-related increase in minor respiratory upset with flunitrazepam in unpremedicated patients and a high frequency of arterial hypotension following large doses given to patients who had received opiate premedication. Venous sequelae were no more frequent than after comparable doses of diazepam. Flunitrazepam was not a very satisfactory drug for the induction of anaesthesia, and recovery was too prolonged for routine use.", "contents": "Clinical studies of induction agents XLIII: Flunitrazepam. Flunitrazepam (Ro 5-4200) has been studied as an induction agent in 220 volunteers or patients. It was assumed to be 10 times as potent as diazepam. The maximum soporific effect did not occur until 90-120 s after injection. There was great individual variation in response to flunitrazepam and some patients did not lose consciousness even after receiving 6 mg (approximately 0.1 mg/kg). Opiate premedication enhanced its action, but delayed recovery. There was a dose-related increase in minor respiratory upset with flunitrazepam in unpremedicated patients and a high frequency of arterial hypotension following large doses given to patients who had received opiate premedication. Venous sequelae were no more frequent than after comparable doses of diazepam. Flunitrazepam was not a very satisfactory drug for the induction of anaesthesia, and recovery was too prolonged for routine use."}
{"id": "PMID:8070", "title": "Salmefamol and Salbutamol in exercise-induced asthma in children.", "content": "A double-blind controlled study is reported of salmefamol 200 mug and salbutamol 200 mug administered by aerosol before exercise tests in asthmatic children. Both drugs prevented exercise-induced asthma. There was no significant difference between them.", "contents": "Salmefamol and Salbutamol in exercise-induced asthma in children. A double-blind controlled study is reported of salmefamol 200 mug and salbutamol 200 mug administered by aerosol before exercise tests in asthmatic children. Both drugs prevented exercise-induced asthma. There was no significant difference between them."}
{"id": "PMID:8071", "title": "The role of divalent cations in epidermolysis.", "content": "In experiments designed to elucidate the role of divalent cations in maintaining the integrity of the epidermis, newborn mouse skin was incubated in ethylenediamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA). In EDTA, epidermolysis occurred and was confirmed by rubbing the specimen to demonstrate that a sheet of epidermis could be split off. After 30 min incubation in 0-01 mol/EDTA the split occurred in the lower granular-upper spinous layer; after 45 min, it was in a spinous-suprabasilar location and at 60 min and later at the dermal-epidermal junction. Ultrastructurally, a clear zone of apparent intracellular oedema occurred along the cell membranes. The split then occurred intracytoplasmally through this clear zone and the adjacent cell membrane was lost. Since incubation in EGTA at pH 7-4 did not result in epidermolysis, we suggest that the removal of magnesium rather than calcium is responsible for epidermolysis. Thirty min after the addition of either calcium or magnesium to EDTA-treated specimens, epidermolysis could no longer be demonstrated.", "contents": "The role of divalent cations in epidermolysis. In experiments designed to elucidate the role of divalent cations in maintaining the integrity of the epidermis, newborn mouse skin was incubated in ethylenediamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA). In EDTA, epidermolysis occurred and was confirmed by rubbing the specimen to demonstrate that a sheet of epidermis could be split off. After 30 min incubation in 0-01 mol/EDTA the split occurred in the lower granular-upper spinous layer; after 45 min, it was in a spinous-suprabasilar location and at 60 min and later at the dermal-epidermal junction. Ultrastructurally, a clear zone of apparent intracellular oedema occurred along the cell membranes. The split then occurred intracytoplasmally through this clear zone and the adjacent cell membrane was lost. Since incubation in EGTA at pH 7-4 did not result in epidermolysis, we suggest that the removal of magnesium rather than calcium is responsible for epidermolysis. Thirty min after the addition of either calcium or magnesium to EDTA-treated specimens, epidermolysis could no longer be demonstrated."}
{"id": "PMID:8073", "title": "Planned pregnancy in a renal transplant recipient.", "content": "A scheme is described for the investigation and management of a renal transplant recipient before conception, over conception and during the subsequent pregnancy, delivery and puerperium. The patient showed the physiological changes in homeostasis of normal pregnancy. Methods of monitoring maternal, fetal and renal well-being are discussed. The patient was delivered of a live male child and the neonatal problems are described. The puerperium was uneventful.", "contents": "Planned pregnancy in a renal transplant recipient. A scheme is described for the investigation and management of a renal transplant recipient before conception, over conception and during the subsequent pregnancy, delivery and puerperium. The patient showed the physiological changes in homeostasis of normal pregnancy. Methods of monitoring maternal, fetal and renal well-being are discussed. The patient was delivered of a live male child and the neonatal problems are described. The puerperium was uneventful."}
{"id": "PMID:8074", "title": "Effect of oral 17-beta-oestradiol on the liver in women with intrahepatic cholestasis (hepatosis) during previous pregnancy.", "content": "The effects of 17-beta-oestradiol in 14 women who had had intrahepatic cholestasis of pregnancy (hepatosis) were studied. This natural oestrogen was given orally in a daily dose of 5 mg for two 20-day periods with a 7-day interval between courses. The bromsulphthalein (BSP) retention rose during the treatment, but only occasionally to levels above the upper limit of normal. Other conventional liver function tests did not usually become abnormal. In a previous investigation in the same type of patients, we studied the effects of mestranol (a synthetic 17-alkylated oestrogen) in a daily dose of 0.1 mg with the same dose-schedule as the present investigation and 17-beta-oestradiol appeared to impair liver function less than mestranol. It might thus be safer to use 17-beta-oestradiol as a therapeutic agent.", "contents": "Effect of oral 17-beta-oestradiol on the liver in women with intrahepatic cholestasis (hepatosis) during previous pregnancy. The effects of 17-beta-oestradiol in 14 women who had had intrahepatic cholestasis of pregnancy (hepatosis) were studied. This natural oestrogen was given orally in a daily dose of 5 mg for two 20-day periods with a 7-day interval between courses. The bromsulphthalein (BSP) retention rose during the treatment, but only occasionally to levels above the upper limit of normal. Other conventional liver function tests did not usually become abnormal. In a previous investigation in the same type of patients, we studied the effects of mestranol (a synthetic 17-alkylated oestrogen) in a daily dose of 0.1 mg with the same dose-schedule as the present investigation and 17-beta-oestradiol appeared to impair liver function less than mestranol. It might thus be safer to use 17-beta-oestradiol as a therapeutic agent."}
{"id": "PMID:8076", "title": "Structural elucidation and properties of 8alpha-(N1-histidyl)riboflavin: the flavin component of thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase.", "content": "In addition to 8alpha-(N3-histidyl)riboflavin, 8alpha-(N1-histidyl)riboflavin is also formed during the reaction of Nalpha-blocked histidine with 8alpha-bromotetraacetylriboflavin in a yield of 20-25% of the total histidylflavin fraction. The properties of 8alpha-(N1-histidyl)riboflavin are inditical with those of the histidylflavin isolated from thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase but differ from those of 8alpha-(N3-histidyl)riboflavin. These properties include pKa of fluorescence quenching, electrophoretic mobility at pH 5.0, stability to storage, and reduction by NaBH4. Proof for 8alpha substitution is shown by the electron paramagnetic resonance and electron-nuclear double resonance spectra of the cationic semiquinone form, as well as by the proton magnetic resonance spectrum of the oxidized form. The site of histidine substitution by the 8alpha-methylene of the flavin moiety was shown by methylation of the imidazole ring with methyl iodide, cleavage of the methylhistidine-flavin bond by acid hydrolysis at 150 degrees C, and identification of the methylhistidine isomer by electrophoresis. 3-Methylhistidine is the product from the N1-histidylflavin isomer, while 1-methylhistidine is produced from the N3 isomer. The flavin product from reductive Zn cleavage of either isomer has been identified as riboflavin. The compound obtained on acid treatment of 8alpha-(N3-histidyl)riboflavin (previously thought to be the N1 isomer) differs from the parent compound only in the ribityl side chain, since chemical degradation studies show 1-methylhistidine as a product and a flavin product which differs from riboflavin only in mobility in thin-layer chromatography, but not in absorption, fluorescence, and electron paramagnetic resonance spectral properties. Proof that acid modification involves only the ribityl chain has come from the observations that alkaline irradiation of this flavin yields lumiflavin, that the proton magnetic resonance spectrum of the compound differs from that of riboflavin in the region of the ribityl proton resonance, and that its periodate titer is lower than that of authentic riboflavin. The identity of 8alpha-(N1-histidyl)riboflavin with the histidylflavin from thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase shows that both isomeric forms of 8alpha-histidylflavin occur in nature.", "contents": "Structural elucidation and properties of 8alpha-(N1-histidyl)riboflavin: the flavin component of thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase. In addition to 8alpha-(N3-histidyl)riboflavin, 8alpha-(N1-histidyl)riboflavin is also formed during the reaction of Nalpha-blocked histidine with 8alpha-bromotetraacetylriboflavin in a yield of 20-25% of the total histidylflavin fraction. The properties of 8alpha-(N1-histidyl)riboflavin are inditical with those of the histidylflavin isolated from thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase but differ from those of 8alpha-(N3-histidyl)riboflavin. These properties include pKa of fluorescence quenching, electrophoretic mobility at pH 5.0, stability to storage, and reduction by NaBH4. Proof for 8alpha substitution is shown by the electron paramagnetic resonance and electron-nuclear double resonance spectra of the cationic semiquinone form, as well as by the proton magnetic resonance spectrum of the oxidized form. The site of histidine substitution by the 8alpha-methylene of the flavin moiety was shown by methylation of the imidazole ring with methyl iodide, cleavage of the methylhistidine-flavin bond by acid hydrolysis at 150 degrees C, and identification of the methylhistidine isomer by electrophoresis. 3-Methylhistidine is the product from the N1-histidylflavin isomer, while 1-methylhistidine is produced from the N3 isomer. The flavin product from reductive Zn cleavage of either isomer has been identified as riboflavin. The compound obtained on acid treatment of 8alpha-(N3-histidyl)riboflavin (previously thought to be the N1 isomer) differs from the parent compound only in the ribityl side chain, since chemical degradation studies show 1-methylhistidine as a product and a flavin product which differs from riboflavin only in mobility in thin-layer chromatography, but not in absorption, fluorescence, and electron paramagnetic resonance spectral properties. Proof that acid modification involves only the ribityl chain has come from the observations that alkaline irradiation of this flavin yields lumiflavin, that the proton magnetic resonance spectrum of the compound differs from that of riboflavin in the region of the ribityl proton resonance, and that its periodate titer is lower than that of authentic riboflavin. The identity of 8alpha-(N1-histidyl)riboflavin with the histidylflavin from thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase shows that both isomeric forms of 8alpha-histidylflavin occur in nature."}
{"id": "PMID:8077", "title": "Energetics of primary processes in visula escitation: photocalorimetry of rhodopsin in rod outer segment membranes.", "content": "A sensitive technique for the direct calorimetric determination of the energetics of photochemical reactions under low levels of illumination, and its application to the study of primary processes in visula excitation, are described. Enthlpies are reported for various steps in the bleaching of rhodopsin in intact rod outer segment membranes, together with the heats of appropriate model reactions. Protonation changes are also determined calorimetrically by use of buffers with differing heats of proton ionization. Bleaching of rhodopsin is accompanied by significant uptake of heat energy, vastly in excess of the energy required for simple isomerization of the retinal chromophore. Metarhodopsin I formation involves the uptake of about 17 kcal/mol and no net change in proton ionization of the system. Formation of metarhodopsin II requires an additional energy of about 10 kcal/mol and involves the uptake on one hydrogen ion from solution. The energetics of the overall photolysis reaction, rhodopsin leads to opsin + all-trans-retinal, are pH dependent and involve the exposure of an additional titrating group on opsin. This group has a heat of proton ionization of about 12 kcal/mal, characteristic of a primary amine, but a pKa in the region of neutrality. We suggest that this group is the Schiff base lysine of the chromophore binding site of rhodopsin which becomes exposed on photolysis. The low pKa for this active lysine would result in a more stable retinal-opsin linkage, and might be induced by a nearby positively charged group on the protein (either arginine or a second lysine residue). This leads to a model involving intramolecular protonation of the Schiff base nitrogen in the retinal-opsin linkage of rhodopsin, which is consistent with the thermodynamic and spectroscopic properties of the system. We further propose that the metarhodopsin I leads to metarhodopsin II step in the bleaching sequence involves reversible hydrolysis of the Schiff base linkage in the chromophore binding site, and that subsequent steps are the result of migration of the chromophore from this site.", "contents": "Energetics of primary processes in visula escitation: photocalorimetry of rhodopsin in rod outer segment membranes. A sensitive technique for the direct calorimetric determination of the energetics of photochemical reactions under low levels of illumination, and its application to the study of primary processes in visula excitation, are described. Enthlpies are reported for various steps in the bleaching of rhodopsin in intact rod outer segment membranes, together with the heats of appropriate model reactions. Protonation changes are also determined calorimetrically by use of buffers with differing heats of proton ionization. Bleaching of rhodopsin is accompanied by significant uptake of heat energy, vastly in excess of the energy required for simple isomerization of the retinal chromophore. Metarhodopsin I formation involves the uptake of about 17 kcal/mol and no net change in proton ionization of the system. Formation of metarhodopsin II requires an additional energy of about 10 kcal/mol and involves the uptake on one hydrogen ion from solution. The energetics of the overall photolysis reaction, rhodopsin leads to opsin + all-trans-retinal, are pH dependent and involve the exposure of an additional titrating group on opsin. This group has a heat of proton ionization of about 12 kcal/mal, characteristic of a primary amine, but a pKa in the region of neutrality. We suggest that this group is the Schiff base lysine of the chromophore binding site of rhodopsin which becomes exposed on photolysis. The low pKa for this active lysine would result in a more stable retinal-opsin linkage, and might be induced by a nearby positively charged group on the protein (either arginine or a second lysine residue). This leads to a model involving intramolecular protonation of the Schiff base nitrogen in the retinal-opsin linkage of rhodopsin, which is consistent with the thermodynamic and spectroscopic properties of the system. We further propose that the metarhodopsin I leads to metarhodopsin II step in the bleaching sequence involves reversible hydrolysis of the Schiff base linkage in the chromophore binding site, and that subsequent steps are the result of migration of the chromophore from this site."}
{"id": "PMID:8078", "title": "Characterization of 20S component in tubulin from mammalian brain.", "content": "Tubulin from porcine brain, purified by at least two cycles of assembly and disassembly, was characerized at different pH values by sedimentation velocity analysis and turbidimetric measurements. At pH 6.4 the depolymerized material was composed of two major species sedimenting with so20,w values of 6 and 36 and a minor one of 20S. By raising the pH, the amount of the 20S component increased and that of the 36S decreased, whereas that of the 6S component was unaltered. At pH 7.6 the mixture contained 20S and 6S components but hardly any 36S. The 20S species can be separated from the 6S ones by gel filtration on agarose A-15m at pH 7.6. On electron microscopic examination this preparation contains far fewer double rings compared to the material at pH 6.4, but single rings could often be seen. Sodium dodecyl sulfate gel electrophoresis of the 20S and 36S components showed that they consist almost entirely of tubulin and some higher and lower molecular weight fractions. Turbidity measurements showed that the minimal protein concentration necessary for polymerization increases with increasing pH. The turbidity plateau reached at a given pH can be raised by decreasing the pH. From these results it is suggested that the 20S component is an intermediate of the 36S species. The results further indicate the existence of a pH-dependent equilibrium between the 20S species and the 36Soligomers.", "contents": "Characterization of 20S component in tubulin from mammalian brain. Tubulin from porcine brain, purified by at least two cycles of assembly and disassembly, was characerized at different pH values by sedimentation velocity analysis and turbidimetric measurements. At pH 6.4 the depolymerized material was composed of two major species sedimenting with so20,w values of 6 and 36 and a minor one of 20S. By raising the pH, the amount of the 20S component increased and that of the 36S decreased, whereas that of the 6S component was unaltered. At pH 7.6 the mixture contained 20S and 6S components but hardly any 36S. The 20S species can be separated from the 6S ones by gel filtration on agarose A-15m at pH 7.6. On electron microscopic examination this preparation contains far fewer double rings compared to the material at pH 6.4, but single rings could often be seen. Sodium dodecyl sulfate gel electrophoresis of the 20S and 36S components showed that they consist almost entirely of tubulin and some higher and lower molecular weight fractions. Turbidity measurements showed that the minimal protein concentration necessary for polymerization increases with increasing pH. The turbidity plateau reached at a given pH can be raised by decreasing the pH. From these results it is suggested that the 20S component is an intermediate of the 36S species. The results further indicate the existence of a pH-dependent equilibrium between the 20S species and the 36Soligomers."}
{"id": "PMID:8079", "title": "Histone interactions in solution and susceptibility to denaturation.", "content": "Histone interactions in solution may depend upon treatments used for purification. Optical rotatory dispersion and sedimentation-velocity measurements have been made in a reference solvent, before and after exposure to various treatments, to investigate histone susceptibility to irreversible denaturation. Some acid conditions and urea and guanidine solutions may denature. Interaction studies performed on nondenatured histones indicate that the dimer, (H4)(H3), and tetramer, (H4)2(H3)2, dissociate to monomers at low ionic strength. Sedimentation-velocity experiments suggest a model for the (H4)2(H3)2 tetramer, with a compact semispherical center and four protruding amino-terminal regions. Fractions H2a and H2b interact to form the mixed dimer in equilibrium with monomers. Fraction H2a self-associates readily to dimers, tetramers, and octamers, while fraction H1 associates only weakly to form dimers.", "contents": "Histone interactions in solution and susceptibility to denaturation. Histone interactions in solution may depend upon treatments used for purification. Optical rotatory dispersion and sedimentation-velocity measurements have been made in a reference solvent, before and after exposure to various treatments, to investigate histone susceptibility to irreversible denaturation. Some acid conditions and urea and guanidine solutions may denature. Interaction studies performed on nondenatured histones indicate that the dimer, (H4)(H3), and tetramer, (H4)2(H3)2, dissociate to monomers at low ionic strength. Sedimentation-velocity experiments suggest a model for the (H4)2(H3)2 tetramer, with a compact semispherical center and four protruding amino-terminal regions. Fractions H2a and H2b interact to form the mixed dimer in equilibrium with monomers. Fraction H2a self-associates readily to dimers, tetramers, and octamers, while fraction H1 associates only weakly to form dimers."}
{"id": "PMID:8080", "title": "Structural analysis of O2'-methyl-5-carbamoylmethyluridine, a newly discovered constituent of yeast transfer RNA.", "content": "A compound tentatively identified as O2-methyl-5-carboxymethyluridine (cm5Um) was recently isolated in this laboratory from bulk yeast transfer RNA (Gray, M. W. (1975), Can, J. Biochem. 53, 735-746). Alkaline hydrolysis of yeast tRNA releases this nucleoside as part of an alkali-stable dinucleotide, cm5Um-Ap, from which sufficient cm5Um was prepared in the present investigation for a detailed examination of its properties. The ultraviolet absorption spectra and chromatographic and electrophoretic properties of cm5Um were consistent with the proposed structure, which was confirmed by characterization of the base and sugar moieties as 5-carboxymethyluracil and 2-O-methylribose, respectively. Snake venom hydrolysis of yeast tRNA releases cm5Um in the form of a carboxyl-blocked 5'-nucleotide, designated pU-2. Identification of the alkali-labile blocking group in pU-2 as an amide was based on quantitative assay for ammonia released upon acid hydrolysis of the corresponding nucleoside, U-2, and by chromatographic comparison of U-2 with the semisynthetic methyl ester and amide derivatives of cm5Um (mcm5Um and ncm5Um, respectively). Quantitative analysis has indicated that ncm5Um may be confined to a single species of yeast tRNA. In view of the unique localization (the \"Wobble\" position of the anticodon sequence) and coding properties (pairing with A but not with G) of other cm5U  derivatives in transfer RNA, the dinucleotide cm5Um-Ap may be derived from the first two positions of the anticodon sequence of a yeast tRNA species recognizing an NUA codon. This predicts that O2-methyl-5-carbamoylmethyluridine will be found in an isoleucine, leucine, or valine isoacceptor.", "contents": "Structural analysis of O2'-methyl-5-carbamoylmethyluridine, a newly discovered constituent of yeast transfer RNA. A compound tentatively identified as O2-methyl-5-carboxymethyluridine (cm5Um) was recently isolated in this laboratory from bulk yeast transfer RNA (Gray, M. W. (1975), Can, J. Biochem. 53, 735-746). Alkaline hydrolysis of yeast tRNA releases this nucleoside as part of an alkali-stable dinucleotide, cm5Um-Ap, from which sufficient cm5Um was prepared in the present investigation for a detailed examination of its properties. The ultraviolet absorption spectra and chromatographic and electrophoretic properties of cm5Um were consistent with the proposed structure, which was confirmed by characterization of the base and sugar moieties as 5-carboxymethyluracil and 2-O-methylribose, respectively. Snake venom hydrolysis of yeast tRNA releases cm5Um in the form of a carboxyl-blocked 5'-nucleotide, designated pU-2. Identification of the alkali-labile blocking group in pU-2 as an amide was based on quantitative assay for ammonia released upon acid hydrolysis of the corresponding nucleoside, U-2, and by chromatographic comparison of U-2 with the semisynthetic methyl ester and amide derivatives of cm5Um (mcm5Um and ncm5Um, respectively). Quantitative analysis has indicated that ncm5Um may be confined to a single species of yeast tRNA. In view of the unique localization (the \"Wobble\" position of the anticodon sequence) and coding properties (pairing with A but not with G) of other cm5U  derivatives in transfer RNA, the dinucleotide cm5Um-Ap may be derived from the first two positions of the anticodon sequence of a yeast tRNA species recognizing an NUA codon. This predicts that O2-methyl-5-carbamoylmethyluridine will be found in an isoleucine, leucine, or valine isoacceptor."}
{"id": "PMID:8081", "title": "Mechanisms of electron transfer from sulfite to horseradish peroxidase-hydroperoxide compounds.", "content": "Using a rapid-scan spectrophotometer equipped with a stopped-flow apparatus, reactions of sulfite with compounds I and II of two horseradish peroxidase isoenzymes A and C were investigated. The direct two-electron reduction of peroxidase compound I by sulfite occurred at acidic pH but the mechanism gradually changed to the two-step reduction with the intermediate formation of compound II as the pH increased. The pH at which the one- and two-electron changes occurred at the same speed was 4.5 for peroxidase A and 7.7 for peroxidase C. A new peroxidase intermediate was found in the reaction between peroxidase compound II and sulfite. The sulfite compound showed a characteristic absorption band at 850 nm and the optical spectrum was similar to that of isoporphyrins but was quite different from that of sulfhemoproteins. The rate (k) of conversion from the sulfite-compound II complex to the sulfite compound was proportional to the concentration of H+ and the log k vs. pH plot for peroxidase A moved to the acidic side by 1.1 pH unit from that for peroxidase C.", "contents": "Mechanisms of electron transfer from sulfite to horseradish peroxidase-hydroperoxide compounds. Using a rapid-scan spectrophotometer equipped with a stopped-flow apparatus, reactions of sulfite with compounds I and II of two horseradish peroxidase isoenzymes A and C were investigated. The direct two-electron reduction of peroxidase compound I by sulfite occurred at acidic pH but the mechanism gradually changed to the two-step reduction with the intermediate formation of compound II as the pH increased. The pH at which the one- and two-electron changes occurred at the same speed was 4.5 for peroxidase A and 7.7 for peroxidase C. A new peroxidase intermediate was found in the reaction between peroxidase compound II and sulfite. The sulfite compound showed a characteristic absorption band at 850 nm and the optical spectrum was similar to that of isoporphyrins but was quite different from that of sulfhemoproteins. The rate (k) of conversion from the sulfite-compound II complex to the sulfite compound was proportional to the concentration of H+ and the log k vs. pH plot for peroxidase A moved to the acidic side by 1.1 pH unit from that for peroxidase C."}
{"id": "PMID:8082", "title": "Vinylglycine and proparglyglycine: complementary suicide substrates for L-amino acid oxidase and D-amino acid oxidase.", "content": "Proparglyglycine (2-amino-4-pentynoate) and vinylglycine (2-amino-3-butenoate) have been examined as substrates and possible inactivators of two flavo enzymes, D-amino acid oxidase from pig kidney and L-amino acid oxidase from Crotalus adamanteus venom. Vinylglycine is rapidly oxidized by both enzymes but only L-amino acid oxidase is inactivated under assay conditions. The loss of activity probably involves covalent modification of an active site residue rather than the flavin adenine dinucleotide coenzyme and occurs once every 20000 turnovers. We have confirmed the recent observation (Horiike, K, Hishina, Y., Miyake, Y., and Yamano, T. (1975) J, Biochem. (Tokyo), 78, 57) that D-proparglglycine is oxidized with a time-dependent loss of activity by D-amino acid oxidase and have examined some mechanistic aspects of this inactivation, The extent of residual oxidase activity, insensitive to further inactivation, is about 2%, at which point 1.7 labels/subunit have been introduced with propargly[2-14C]glycine as substrate. L-Proparglyclycine is a substrate but not an inactivator of L-amino acid oxidase and the product ahat accumulats in the nonnucleophilic N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer is acetopyruvate. In the presence of butylamine HCl, a species with lambdaman 317 nm (epsilon = 15 000) accumulates that may be a conjugated eneamine adduct. The same species accumulates from D-amino acid oxidase oxidation of D-propargylglycine prior to inactivation; the inactivated apo D-amino acid oxidase has a new peak at 317 nm that is probably a similar eneamine. A likely inactivating species is 2-keto-3,4-pentadienoate arising from facile rearrangement of the expected initial product 2-keto 4 pentynoate. Vinylglycine and proparglyglycine show inactivation specificity, then, for L-and D-amino acid oxidase, respectively.", "contents": "Vinylglycine and proparglyglycine: complementary suicide substrates for L-amino acid oxidase and D-amino acid oxidase. Proparglyglycine (2-amino-4-pentynoate) and vinylglycine (2-amino-3-butenoate) have been examined as substrates and possible inactivators of two flavo enzymes, D-amino acid oxidase from pig kidney and L-amino acid oxidase from Crotalus adamanteus venom. Vinylglycine is rapidly oxidized by both enzymes but only L-amino acid oxidase is inactivated under assay conditions. The loss of activity probably involves covalent modification of an active site residue rather than the flavin adenine dinucleotide coenzyme and occurs once every 20000 turnovers. We have confirmed the recent observation (Horiike, K, Hishina, Y., Miyake, Y., and Yamano, T. (1975) J, Biochem. (Tokyo), 78, 57) that D-proparglglycine is oxidized with a time-dependent loss of activity by D-amino acid oxidase and have examined some mechanistic aspects of this inactivation, The extent of residual oxidase activity, insensitive to further inactivation, is about 2%, at which point 1.7 labels/subunit have been introduced with propargly[2-14C]glycine as substrate. L-Proparglyclycine is a substrate but not an inactivator of L-amino acid oxidase and the product ahat accumulats in the nonnucleophilic N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer is acetopyruvate. In the presence of butylamine HCl, a species with lambdaman 317 nm (epsilon = 15 000) accumulates that may be a conjugated eneamine adduct. The same species accumulates from D-amino acid oxidase oxidation of D-propargylglycine prior to inactivation; the inactivated apo D-amino acid oxidase has a new peak at 317 nm that is probably a similar eneamine. A likely inactivating species is 2-keto-3,4-pentadienoate arising from facile rearrangement of the expected initial product 2-keto 4 pentynoate. Vinylglycine and proparglyglycine show inactivation specificity, then, for L-and D-amino acid oxidase, respectively."}
{"id": "PMID:8083", "title": "Properties of crystalline reduced nicotinamide adenine dinucleotide phosphate-adrenodoxin reductase from bovine adrenocortical mitochondria. II. Essential histidyl and cysteinyl residues at the NADPH binding site of NADPH-adrenodoxin reductase.", "content": "The binding site of NADPH in NADPH-adrenodoxin reductase was examined using crystalline enzyme from bovine adrenocortical mitochondria by studies on the effects of photooxidation and chemical modifications of amino acid residues in the reductase. (1) Photoxication decreased the enzymatic activity of NADPH-adrenodoxin reductase. Photooxidation of the reductase was prevented by NADP+, adrenodoxin, or reduced glutathione, but not NAD+. Photoinactivation caused loss of a histidyl residue, but not of tyrosyl, tryptophanyl, cysteinyl, or methionyl residues of the reductase. It did not affect the circular dichroism spectrum of the reductase appreciably. (2) NADPH-adrenodoxin reductase activity was inhibited by diethyl pyrocarbonate and the inhibition was partially reversed by addition of hydroxylamine. The inhibition was prevented by NADP+, but not NAD+. (3) NADPH-adrenodoxin reductase activity was inhibited by 5,5'-dithiobis(2-nitrobenzoate) and the inhibition was reversed by reduced glutathione. It was also protected by NADP+, but not NAD+. The results indicate that a histidyl residue and a cysteinyl residue of NADPH-adrenodoxin reductase are essential for the binding of NADPH by the reductase.", "contents": "Properties of crystalline reduced nicotinamide adenine dinucleotide phosphate-adrenodoxin reductase from bovine adrenocortical mitochondria. II. Essential histidyl and cysteinyl residues at the NADPH binding site of NADPH-adrenodoxin reductase. The binding site of NADPH in NADPH-adrenodoxin reductase was examined using crystalline enzyme from bovine adrenocortical mitochondria by studies on the effects of photooxidation and chemical modifications of amino acid residues in the reductase. (1) Photoxication decreased the enzymatic activity of NADPH-adrenodoxin reductase. Photooxidation of the reductase was prevented by NADP+, adrenodoxin, or reduced glutathione, but not NAD+. Photoinactivation caused loss of a histidyl residue, but not of tyrosyl, tryptophanyl, cysteinyl, or methionyl residues of the reductase. It did not affect the circular dichroism spectrum of the reductase appreciably. (2) NADPH-adrenodoxin reductase activity was inhibited by diethyl pyrocarbonate and the inhibition was partially reversed by addition of hydroxylamine. The inhibition was prevented by NADP+, but not NAD+. (3) NADPH-adrenodoxin reductase activity was inhibited by 5,5'-dithiobis(2-nitrobenzoate) and the inhibition was reversed by reduced glutathione. It was also protected by NADP+, but not NAD+. The results indicate that a histidyl residue and a cysteinyl residue of NADPH-adrenodoxin reductase are essential for the binding of NADPH by the reductase."}
{"id": "PMID:8084", "title": "Steric effects on penicillin-sensitive peptidoglycan synthesis in a membrane-wall system Gaffkya homari.", "content": "Residues 4 and 5 of the pentapeptide moiety, R-Ala1-DGlu2-Lys3-DAla4-DAla5, of peptidoglycan play an important role in the donor phase of cross-linked glycan synthesis. To assess the role of these residues in this phase, a series of UDP-MurNAc-peptides were biosynthesized with residues 4 and 5 replaced singly by either D-alpha-amino-n-butyric acid, D-norvaline, or D-valine. The six nucleotides were compared with UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla (reference) in nascent (penicillin-insensitive) peptidoglycan synthesis and in penicillin-sensitive peptidoglycan synthesis. The synthesis of penicillin-sensitive peptidoglycan is catalyzed by membrane-walls isolated from Gaffkya homari and would appear to require the concerted action of transglycosylase and transpeptidase. The membrane-wall system shows a high degree of discrimination for the steric substituents, -CH3 and -CH2CH3, in residue 4. For example, for UDP-MurNAc-Ala-DGly-Lys-DAbu-DAla and -Ala-DGlu-Lys-DAla-DAbu, Vmax/km is 0.19 and 0.95 and Vmax is 0.03 and 0.52, respectively, of the value for the reference nucleotide. In contrast, for the synthesis of nascent peptidoglycan with these nucleotides Vmax/Km is 0.75 and 0.80, and Vmax is 0.71 and 1.0, respectively, of the value for the reference nucleotide. This trend was also illustrated with the other nucleotides in the time course experiments. These results indicate that the penicillin-sensitive enzyme(s), presumably the transpeptidase, has a higher degree of specificity in the donor phase for D-alanine in residue 4 than for D-alanine in residue 5 in the cross-linking stage of peptidoglycan synthesis.", "contents": "Steric effects on penicillin-sensitive peptidoglycan synthesis in a membrane-wall system Gaffkya homari. Residues 4 and 5 of the pentapeptide moiety, R-Ala1-DGlu2-Lys3-DAla4-DAla5, of peptidoglycan play an important role in the donor phase of cross-linked glycan synthesis. To assess the role of these residues in this phase, a series of UDP-MurNAc-peptides were biosynthesized with residues 4 and 5 replaced singly by either D-alpha-amino-n-butyric acid, D-norvaline, or D-valine. The six nucleotides were compared with UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla (reference) in nascent (penicillin-insensitive) peptidoglycan synthesis and in penicillin-sensitive peptidoglycan synthesis. The synthesis of penicillin-sensitive peptidoglycan is catalyzed by membrane-walls isolated from Gaffkya homari and would appear to require the concerted action of transglycosylase and transpeptidase. The membrane-wall system shows a high degree of discrimination for the steric substituents, -CH3 and -CH2CH3, in residue 4. For example, for UDP-MurNAc-Ala-DGly-Lys-DAbu-DAla and -Ala-DGlu-Lys-DAla-DAbu, Vmax/km is 0.19 and 0.95 and Vmax is 0.03 and 0.52, respectively, of the value for the reference nucleotide. In contrast, for the synthesis of nascent peptidoglycan with these nucleotides Vmax/Km is 0.75 and 0.80, and Vmax is 0.71 and 1.0, respectively, of the value for the reference nucleotide. This trend was also illustrated with the other nucleotides in the time course experiments. These results indicate that the penicillin-sensitive enzyme(s), presumably the transpeptidase, has a higher degree of specificity in the donor phase for D-alanine in residue 4 than for D-alanine in residue 5 in the cross-linking stage of peptidoglycan synthesis."}
{"id": "PMID:8085", "title": "Role of ribosomal RNA methylases in the regulation of ribosome production in mammalian cells.", "content": "The activity of rRNA methylases was stimulated by high-energy precursors of RNA (ribonucleoside triphosphates) and inhibited by degradation products of RNA (ribonucleotides and oligoribonucleotides). The response of methylases from rat Novikoff ascites tumor and liver to these metabolites was strikingly different. The highly active tumor enzymes responded preferentially to inhibition by catabolic metabolites, whereas the less active liver enzymes responded exclusively to stimulation by anabolic metabolites. When the activity of rRNA methylases was assayed in response to increasing concentration of S-adenosylmethionine, the tumor enzymes responded with a hyperbolic substrate dependence curve and the liver enzymes with a sigmoidal curve. In the presence of an inhibitory dinucleotide, ApA, the tumor enzymes responded with a sigmoidal curve; in the presence of a stimulator, adenosine 5'-triphosphate, the liver enzymes responded with a hyperbolic substrate concentration curve. When normal rats were subject to a series of treatments by thioacetamide, a hepatocarcinogen, the liver nucleolar rRNA methylases became responsive to inhibition by ApA and relatively unresponsive to stimulation by adenosine 5'-triphosphate. When tumor-bearing rats were treated with polyinosinate:polycytidylate, an antitumor agent, the tumor nucleolar rRNA methylases became unresponsive to inhibition by ApA and more responsive to stimulation by adenosine 5'-triphosphate. A correlation was noted between increased methylation efficiency in vivo and increased stability of nucleolar RNA during incubation in vitro, or vice versa. These results are interpreted to indicate that rRNAmethylases are regulated by cellular metabolites during the nucleolar biosynthesis of ribosomes and that rRNA methylases may provide a favorable site for selective action by cancer chemotherapeutic agents.", "contents": "Role of ribosomal RNA methylases in the regulation of ribosome production in mammalian cells. The activity of rRNA methylases was stimulated by high-energy precursors of RNA (ribonucleoside triphosphates) and inhibited by degradation products of RNA (ribonucleotides and oligoribonucleotides). The response of methylases from rat Novikoff ascites tumor and liver to these metabolites was strikingly different. The highly active tumor enzymes responded preferentially to inhibition by catabolic metabolites, whereas the less active liver enzymes responded exclusively to stimulation by anabolic metabolites. When the activity of rRNA methylases was assayed in response to increasing concentration of S-adenosylmethionine, the tumor enzymes responded with a hyperbolic substrate dependence curve and the liver enzymes with a sigmoidal curve. In the presence of an inhibitory dinucleotide, ApA, the tumor enzymes responded with a sigmoidal curve; in the presence of a stimulator, adenosine 5'-triphosphate, the liver enzymes responded with a hyperbolic substrate concentration curve. When normal rats were subject to a series of treatments by thioacetamide, a hepatocarcinogen, the liver nucleolar rRNA methylases became responsive to inhibition by ApA and relatively unresponsive to stimulation by adenosine 5'-triphosphate. When tumor-bearing rats were treated with polyinosinate:polycytidylate, an antitumor agent, the tumor nucleolar rRNA methylases became unresponsive to inhibition by ApA and more responsive to stimulation by adenosine 5'-triphosphate. A correlation was noted between increased methylation efficiency in vivo and increased stability of nucleolar RNA during incubation in vitro, or vice versa. These results are interpreted to indicate that rRNAmethylases are regulated by cellular metabolites during the nucleolar biosynthesis of ribosomes and that rRNA methylases may provide a favorable site for selective action by cancer chemotherapeutic agents."}
{"id": "PMID:8086", "title": "Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase.", "content": "The monophoton counting technique was used to obtain the fluorescence decay kinetics of NADH (dihydronicotinamide adenine dinucleotide) bound to LADH (HORSE LIVER ALCOHOL DEHYDROGENAS). It was found that the fluorescence decay of the enzyme complex did not follow a single exponential decay law but that the data could be well described as a sum of two exponentials. The decay parameters of the enzyme complex do not depend on the degree of binding-site saturation. These results are interpreted in terms of a reversible excited-state reaction forming a nonfluorescent product. Fluorescence decay kinetics are also reported for NADH and related molecules in solution. The decay parameters, fluorescence emission maxima, and fluorescence intensities depend on solvent polarity and viscosity.", "contents": "Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase. The monophoton counting technique was used to obtain the fluorescence decay kinetics of NADH (dihydronicotinamide adenine dinucleotide) bound to LADH (HORSE LIVER ALCOHOL DEHYDROGENAS). It was found that the fluorescence decay of the enzyme complex did not follow a single exponential decay law but that the data could be well described as a sum of two exponentials. The decay parameters of the enzyme complex do not depend on the degree of binding-site saturation. These results are interpreted in terms of a reversible excited-state reaction forming a nonfluorescent product. Fluorescence decay kinetics are also reported for NADH and related molecules in solution. The decay parameters, fluorescence emission maxima, and fluorescence intensities depend on solvent polarity and viscosity."}
{"id": "PMID:8087", "title": "pH dependence of the hydrolysis of hippuric acid esters by carboxypeptidase A.", "content": "The pH dependence (pH 4.5-10.5) of the hydrolysis of seven hippuric acid esters (C6H5CONHCH2C-O2CR1R2CO2H: 1a: R1 = R2 = H; 1b: R1 = R2 = CH3; 1c: R1 = H, R2 = p-ClC6H4; 1d: R1 = H, R2 = C2H5; 1e: R1 = H, R2 = (CH3)2CHCH2; 1f: R1 = H, R2 = C6H5; 1g: R1 = H, R2 = C6H5CH2) by bovine carboxypeptidase A has been investigated, and the pH dependence of the substrate activation of 1a-c and the substrate inhibition of 1d-g have been compared. For all seven esters the catalytically productive binding of the first substrate molecule depends on enzymatic pKa values of 6.0 and 9.1. For 1d, 1e, and 1g the rate of hydrolysis (k2app) of this complex is pH independent, whereas for 1f k2app depends on a pKa of 5.9. The rate of hydrolysis (k3app) of the 1:2 enzyme-substrate complex (ES2) is pH independent for 1d-g, but for 1a-c k3app depends on the following pKa values: 1a, 6.1 and 9.1; 1b, 5.4; 1c, 6.6. The pH dependences of k2app for 1f and k3app for 1c are rationalized by the presence of catalytically nonproductive species. Equivalent ES2 species are believed to be productive for 1c-g; however, the productive ES2 species for 1b must be quite different.", "contents": "pH dependence of the hydrolysis of hippuric acid esters by carboxypeptidase A. The pH dependence (pH 4.5-10.5) of the hydrolysis of seven hippuric acid esters (C6H5CONHCH2C-O2CR1R2CO2H: 1a: R1 = R2 = H; 1b: R1 = R2 = CH3; 1c: R1 = H, R2 = p-ClC6H4; 1d: R1 = H, R2 = C2H5; 1e: R1 = H, R2 = (CH3)2CHCH2; 1f: R1 = H, R2 = C6H5; 1g: R1 = H, R2 = C6H5CH2) by bovine carboxypeptidase A has been investigated, and the pH dependence of the substrate activation of 1a-c and the substrate inhibition of 1d-g have been compared. For all seven esters the catalytically productive binding of the first substrate molecule depends on enzymatic pKa values of 6.0 and 9.1. For 1d, 1e, and 1g the rate of hydrolysis (k2app) of this complex is pH independent, whereas for 1f k2app depends on a pKa of 5.9. The rate of hydrolysis (k3app) of the 1:2 enzyme-substrate complex (ES2) is pH independent for 1d-g, but for 1a-c k3app depends on the following pKa values: 1a, 6.1 and 9.1; 1b, 5.4; 1c, 6.6. The pH dependences of k2app for 1f and k3app for 1c are rationalized by the presence of catalytically nonproductive species. Equivalent ES2 species are believed to be productive for 1c-g; however, the productive ES2 species for 1b must be quite different."}
{"id": "PMID:8088", "title": "Pulse fluorimetry study of beef liver glutamate dehydrogenase reduced nicotinamide adenine dinucleotide phosphate complexes.", "content": "Single photon counting pulse fluorimetry has been used in order to study the two ternary complexes GDH-GTP-NADPH and GDH-L-glutamate-NADPH and the quaternary complex GDH-GTP-L-glutamate-NADPH. The fluorescence decay of the enzyme-bound NADPH is not monoexponential in any of these complexes. Moreover, it does not seem to be dependent on the coenzyme concentration. The experimental curves can be satisfactorily fitted with the sum of two exponentials, the relative amplitudes of which significantly depend on the complex studied. Thus, for dihydronicotinamide two possible environments  might exist in the enzyme active sites. It is also shown that the fluorescence decay times of the enzyme are shortened by the bound NADPH.", "contents": "Pulse fluorimetry study of beef liver glutamate dehydrogenase reduced nicotinamide adenine dinucleotide phosphate complexes. Single photon counting pulse fluorimetry has been used in order to study the two ternary complexes GDH-GTP-NADPH and GDH-L-glutamate-NADPH and the quaternary complex GDH-GTP-L-glutamate-NADPH. The fluorescence decay of the enzyme-bound NADPH is not monoexponential in any of these complexes. Moreover, it does not seem to be dependent on the coenzyme concentration. The experimental curves can be satisfactorily fitted with the sum of two exponentials, the relative amplitudes of which significantly depend on the complex studied. Thus, for dihydronicotinamide two possible environments  might exist in the enzyme active sites. It is also shown that the fluorescence decay times of the enzyme are shortened by the bound NADPH."}
{"id": "PMID:8089", "title": "Binding of phosphorylcholine to an IgM Waldenstr\u00f6m as studied by fluorescence spectroscopy and circular dichroism.", "content": "The binding characteristics of an IgM Waldenstr\u00f6m(FR) for the ligand phosphorylcholine has been studied by fluorescence spectroscopy. Upon phosphorylcholine addition, IgM FR exhibited 83% enhancement of the tryptophanyl fluorescence, which was associated with a red shift of the emission maximun (5nm). The same properties were observed with the 7S IgM subunits. The association constant KA for phosphorylcholine was 6X10(4) M-1 FOR IgM FR and the 7S subunit, as determined by fluorescence titration, a value in agreement with the obtained by equilibrium dialysis. No significant decrease in the KA value was found in the presence of 3 M urea; in 6 M urea, the increase in fluorescence intensity was 36% of the value obtained in the absence of denaturing agent. In contrast, only 4% of fluorescence enhancement was noted upon binding in 3 M GuHC1 and no enhancement could be seen when the concentration of  GuHC1 was increased to 5 M, thus suggesting complete unfolding of the protein and subsequent loss of binding activity. The pH dependence study of the phosphorylcholine binding to IgM FR indicated no significant differences in the fluorescence enhancement between pH 5 and 8, whereas at more acidic or alkaline pH values, the enhancement became smaller. At pH 3.0 and 10.0, no enhancement was seen suggesting no binding of the ligand, a fact confirmed independently by equilibrium dialysis. When the spectroscopic properties of the IgM FR were compared with those of murine myeloma proteins that bind the same ligand large differences were recorded in the amplitude of the  phosphorylcholine induced enhancement of the fluorescnece and in the shift of the emission maximum wavelength. This suggests that the human and murine proteins interact differently with the small ligand phosphorylcholine thus implying that the variable domains of these molecules are not identical", "contents": "Binding of phosphorylcholine to an IgM Waldenstr\u00f6m as studied by fluorescence spectroscopy and circular dichroism. The binding characteristics of an IgM Waldenstr\u00f6m(FR) for the ligand phosphorylcholine has been studied by fluorescence spectroscopy. Upon phosphorylcholine addition, IgM FR exhibited 83% enhancement of the tryptophanyl fluorescence, which was associated with a red shift of the emission maximun (5nm). The same properties were observed with the 7S IgM subunits. The association constant KA for phosphorylcholine was 6X10(4) M-1 FOR IgM FR and the 7S subunit, as determined by fluorescence titration, a value in agreement with the obtained by equilibrium dialysis. No significant decrease in the KA value was found in the presence of 3 M urea; in 6 M urea, the increase in fluorescence intensity was 36% of the value obtained in the absence of denaturing agent. In contrast, only 4% of fluorescence enhancement was noted upon binding in 3 M GuHC1 and no enhancement could be seen when the concentration of  GuHC1 was increased to 5 M, thus suggesting complete unfolding of the protein and subsequent loss of binding activity. The pH dependence study of the phosphorylcholine binding to IgM FR indicated no significant differences in the fluorescence enhancement between pH 5 and 8, whereas at more acidic or alkaline pH values, the enhancement became smaller. At pH 3.0 and 10.0, no enhancement was seen suggesting no binding of the ligand, a fact confirmed independently by equilibrium dialysis. When the spectroscopic properties of the IgM FR were compared with those of murine myeloma proteins that bind the same ligand large differences were recorded in the amplitude of the  phosphorylcholine induced enhancement of the fluorescnece and in the shift of the emission maximum wavelength. This suggests that the human and murine proteins interact differently with the small ligand phosphorylcholine thus implying that the variable domains of these molecules are not identical"}
{"id": "PMID:8090", "title": "pH dependence of tritium exchange with the C-2 protons of the histidines in bovine trypsin.", "content": "At pH 8.9 and 37 degrees C the half-times for tritium exchange with the C-2 protons of the histidines of trypsin are 73 days for His-57, and greater than 1000 days for His-40 and His-91. These half-times are much longer than the half-life of exchange for the C-2 proton of free histidine (2.8 days at pD 8.2), and longer than any previously reported half-time of exchange at pH greater than 8. These very low rates of exchange are discussed with reference to the refined structure of trypsin. The tritium exchange of His-57 depends on an apparent pKa of 6.6. This pKa may represent the pKa of the imidazole of His-57 in an inactive conformation of the enzyme.", "contents": "pH dependence of tritium exchange with the C-2 protons of the histidines in bovine trypsin. At pH 8.9 and 37 degrees C the half-times for tritium exchange with the C-2 protons of the histidines of trypsin are 73 days for His-57, and greater than 1000 days for His-40 and His-91. These half-times are much longer than the half-life of exchange for the C-2 proton of free histidine (2.8 days at pD 8.2), and longer than any previously reported half-time of exchange at pH greater than 8. These very low rates of exchange are discussed with reference to the refined structure of trypsin. The tritium exchange of His-57 depends on an apparent pKa of 6.6. This pKa may represent the pKa of the imidazole of His-57 in an inactive conformation of the enzyme."}
{"id": "PMID:8091", "title": "Multiple acyl-coenzyme A carboxylases in Pseudomonas citronellolis.", "content": "Pseudomonas citronellolis was shown to contain four different acyl-coenzyme A carboxylases, including acetyl-, propionyl-, 3-methylcrotonyl-, and geranyl-CoA carboxylases, when grown on the appropriate carbon sources. Acetyl-CoA carboxylase activity in crude extracts was stimulated approximately 40-fold by inclusion of 0.4-0.5 M ammonium sulfate in the assay. Unexpectedly high levels of propionyl-CoA carboxylase activity, also stimulated by ammonium sulfate, were found in acetate-grown cells. That these acetyl- and propionyl-CoA carboxylase activities were due to different enzymes was shown by their resolution during purification by a procedure that stabilized acetyl-CoA carboxylase as a complex and separated propionyl-CoA carboxylase into two required protein fractions. Propionate- or valine-grown cells contained a propionyl-CoA carboxylase activity that was strongly inhibited by ammonium sulfate in the assay, and which may represent an inducible form of the enzyme. Geranyl- and 3-methylcrotonyl-CoA carboxylases that catalyze the carboxylation of the 3-methyl groups of homologous acyl-CoA acceptors, were induced by growth on the monoterpenes, citronellic or geranoic acid; only 3-methylcrotonyl-CoA carboxylase was induced by growth on leucine or isovaleric acid. Induction of either carboxylase was associated with the appearance of similar high-molecular-weight, biotin-containing proteins as measured by gel filtration. These two carboxylases are probably distinct enzymes since 3-methyl-crotonyl-CoA carboxylase from isovalerate-grown cells does not carboxylate geranyl-CoA, while geranyl-CoA carboxylase will carboxylate both acyl-CoA homologues. P. citronellolis appears to be a useful system for studying the structural aspects of pairs of homologous acyl-CoA carboxylases.", "contents": "Multiple acyl-coenzyme A carboxylases in Pseudomonas citronellolis. Pseudomonas citronellolis was shown to contain four different acyl-coenzyme A carboxylases, including acetyl-, propionyl-, 3-methylcrotonyl-, and geranyl-CoA carboxylases, when grown on the appropriate carbon sources. Acetyl-CoA carboxylase activity in crude extracts was stimulated approximately 40-fold by inclusion of 0.4-0.5 M ammonium sulfate in the assay. Unexpectedly high levels of propionyl-CoA carboxylase activity, also stimulated by ammonium sulfate, were found in acetate-grown cells. That these acetyl- and propionyl-CoA carboxylase activities were due to different enzymes was shown by their resolution during purification by a procedure that stabilized acetyl-CoA carboxylase as a complex and separated propionyl-CoA carboxylase into two required protein fractions. Propionate- or valine-grown cells contained a propionyl-CoA carboxylase activity that was strongly inhibited by ammonium sulfate in the assay, and which may represent an inducible form of the enzyme. Geranyl- and 3-methylcrotonyl-CoA carboxylases that catalyze the carboxylation of the 3-methyl groups of homologous acyl-CoA acceptors, were induced by growth on the monoterpenes, citronellic or geranoic acid; only 3-methylcrotonyl-CoA carboxylase was induced by growth on leucine or isovaleric acid. Induction of either carboxylase was associated with the appearance of similar high-molecular-weight, biotin-containing proteins as measured by gel filtration. These two carboxylases are probably distinct enzymes since 3-methyl-crotonyl-CoA carboxylase from isovalerate-grown cells does not carboxylate geranyl-CoA, while geranyl-CoA carboxylase will carboxylate both acyl-CoA homologues. P. citronellolis appears to be a useful system for studying the structural aspects of pairs of homologous acyl-CoA carboxylases."}
{"id": "PMID:8092", "title": "Role of bound calcium ions in thermostable, proteolytic enzymes. Separation of intrinsic and calcium ion contributions to the kinetic thermal stability.", "content": "The total kinetic thermal stability of a protein molecule, expressed as the total free energy of activation in thermal denaturation reactions, can be separated into an intrinsic contribution of the polypeptide chain and a contribution due to the binding of calcium ions. The theory for this procedure is applied to thermal denaturation data, obtained at the pH of optimum stability, for the serine proteases, thermomycolase and subtilisin types Carlsberg and BPN', and for the zinc metalloendopeptidases, thermolysin and neutral protease A. The results, obtained from Arrhenius plots at high and low free calcium ion concentrations, reveal a considerable variation in the calcium ion contribution to the total kinetic thermal stability of the various enzymes. In the serine protease group, at 70 degrees C, the stability is largest for thermomycolase, mainly due to a relatively high intrinsic contribution. For the metalloendopeptidases the total kinetic thermal stability is largest for thermolysin, the difference between thermolysin and neutral protease A being dominated by bound calcium ion contributions. The intrinsic kinetic thermal stability of the polypeptide chain of thermolysin is considerably smaller than that of any of the serine proteases and is probably of the same order of magnitude as that of neutral protease A. Thus, the well known total kinetic thermal stability of thermolysin is due mainly to a single calcium ion (Voordouw, G., and Roche, R. S. (1975), Biochemistry 14, 4667) that binds with high affinity even at very high temperatures (K congruent to 6 X 10(7) M-1 at 80 degrees C).", "contents": "Role of bound calcium ions in thermostable, proteolytic enzymes. Separation of intrinsic and calcium ion contributions to the kinetic thermal stability. The total kinetic thermal stability of a protein molecule, expressed as the total free energy of activation in thermal denaturation reactions, can be separated into an intrinsic contribution of the polypeptide chain and a contribution due to the binding of calcium ions. The theory for this procedure is applied to thermal denaturation data, obtained at the pH of optimum stability, for the serine proteases, thermomycolase and subtilisin types Carlsberg and BPN', and for the zinc metalloendopeptidases, thermolysin and neutral protease A. The results, obtained from Arrhenius plots at high and low free calcium ion concentrations, reveal a considerable variation in the calcium ion contribution to the total kinetic thermal stability of the various enzymes. In the serine protease group, at 70 degrees C, the stability is largest for thermomycolase, mainly due to a relatively high intrinsic contribution. For the metalloendopeptidases the total kinetic thermal stability is largest for thermolysin, the difference between thermolysin and neutral protease A being dominated by bound calcium ion contributions. The intrinsic kinetic thermal stability of the polypeptide chain of thermolysin is considerably smaller than that of any of the serine proteases and is probably of the same order of magnitude as that of neutral protease A. Thus, the well known total kinetic thermal stability of thermolysin is due mainly to a single calcium ion (Voordouw, G., and Roche, R. S. (1975), Biochemistry 14, 4667) that binds with high affinity even at very high temperatures (K congruent to 6 X 10(7) M-1 at 80 degrees C)."}
{"id": "PMID:8093", "title": "Reinvestigation of the phenacyl bromide modification of alpha-chymotrypsin.", "content": "The modification of alpha-chymotrysin with phenacyl bromide has been reinvestigated over a wide pH range. Evidence is presented that indicates that the nature of the phenacyl-modified enzymes prepared by this reaction is dependent upon the pH of the reaction medium. The phenacyl alpha-chymotrypsin produced at low pH is most probably the Met-192 phenacylsulfonium salt, as proposed earlier, since it readily undergoes dealkylation using 2-mercaptoethanol. However, the phenacyl-enzyme prepared at neutral pH possesses a much reduced enzymatic activity and does not react with 2-mercaptoethanol to regenerate native alpha-chymotrypsin. In addition, incubation of the Met-192 phenacyl sulfonium enzyme at neutral pH causes a smooth irreversible change to the new phenacyl-enzyme as monitored by changes in enzymatic activity, susceptibility to dealkylation using 2-mercaptoethanol, and ultraviolet difference absorption spectral properties. The stoichiometries of both the low and neutral pH modification reactions have been determined, using [carbonyl-14C]phyenacyl bromide, to be 1 phenacyl group/enzyme molecule. In efforts to obtain information about the nature and mechanism of formation of the phenacyl alpha-chymotrypsin produced at neutral pH, alkylation reactions of modified alpha-chymotrypsins produced by His-57 functionalization with tosylphenylalanine chloromethyl ketone and by Met-192 oxidation to the sulfoxide have been investigated. The combined results of these studies have been initially interpreted in terms of a neutral pH, phenacyl bromide modification resulting in formation of a new modified enzyme via the Met-192 sulfonium salt.", "contents": "Reinvestigation of the phenacyl bromide modification of alpha-chymotrypsin. The modification of alpha-chymotrysin with phenacyl bromide has been reinvestigated over a wide pH range. Evidence is presented that indicates that the nature of the phenacyl-modified enzymes prepared by this reaction is dependent upon the pH of the reaction medium. The phenacyl alpha-chymotrypsin produced at low pH is most probably the Met-192 phenacylsulfonium salt, as proposed earlier, since it readily undergoes dealkylation using 2-mercaptoethanol. However, the phenacyl-enzyme prepared at neutral pH possesses a much reduced enzymatic activity and does not react with 2-mercaptoethanol to regenerate native alpha-chymotrypsin. In addition, incubation of the Met-192 phenacyl sulfonium enzyme at neutral pH causes a smooth irreversible change to the new phenacyl-enzyme as monitored by changes in enzymatic activity, susceptibility to dealkylation using 2-mercaptoethanol, and ultraviolet difference absorption spectral properties. The stoichiometries of both the low and neutral pH modification reactions have been determined, using [carbonyl-14C]phyenacyl bromide, to be 1 phenacyl group/enzyme molecule. In efforts to obtain information about the nature and mechanism of formation of the phenacyl alpha-chymotrypsin produced at neutral pH, alkylation reactions of modified alpha-chymotrypsins produced by His-57 functionalization with tosylphenylalanine chloromethyl ketone and by Met-192 oxidation to the sulfoxide have been investigated. The combined results of these studies have been initially interpreted in terms of a neutral pH, phenacyl bromide modification resulting in formation of a new modified enzyme via the Met-192 sulfonium salt."}
{"id": "PMID:8094", "title": "Evidence for more than one Ca2+ transport mechanism in mitochondria.", "content": "The active transport and internal binding of the Ca2+ analogue Mn2+ by rat liver mitochondria were monitored with electron paramagnetic resonance. The binding of transported Mn2+ depended strongly on internal pH over the range 7.7-8.9. Gradients of free Mn2+ were compared with K+ gradients measured on valinomycin-treated samples. In the steady state, the electrochemical Mn2+ activity was larger outside than inside the mitochondria. The observed gradients of free Mn2+ and of H+ could not be explained by a single \"passive\" uniport or antiport mechanism of divalent cation transport. This conclusion was further substantiated by observed changes in steady-state Ca2+ and Mn2+ distributions induced by La3+ and ruthenium red. Ruthenium red reduced total Ca2+ or Mn2+ uptake, and both inhibitors caused release of divalent cation from preloaded mitochondria. A model is proposed in which divalent cations are transported by at least two mechanisms: (1) a passive uniport and (2) and active pump, cation antiport or anion symport. The former is more sensitive to La3+ and ruthenium red. Under energized steady-state conditions, the net flux of Ca2+ or Mn2+ is inward over (1) and outward over (2). The need for more than one transport system inregulating cytoplasmic Ca2+ is discussed.", "contents": "Evidence for more than one Ca2+ transport mechanism in mitochondria. The active transport and internal binding of the Ca2+ analogue Mn2+ by rat liver mitochondria were monitored with electron paramagnetic resonance. The binding of transported Mn2+ depended strongly on internal pH over the range 7.7-8.9. Gradients of free Mn2+ were compared with K+ gradients measured on valinomycin-treated samples. In the steady state, the electrochemical Mn2+ activity was larger outside than inside the mitochondria. The observed gradients of free Mn2+ and of H+ could not be explained by a single \"passive\" uniport or antiport mechanism of divalent cation transport. This conclusion was further substantiated by observed changes in steady-state Ca2+ and Mn2+ distributions induced by La3+ and ruthenium red. Ruthenium red reduced total Ca2+ or Mn2+ uptake, and both inhibitors caused release of divalent cation from preloaded mitochondria. A model is proposed in which divalent cations are transported by at least two mechanisms: (1) a passive uniport and (2) and active pump, cation antiport or anion symport. The former is more sensitive to La3+ and ruthenium red. Under energized steady-state conditions, the net flux of Ca2+ or Mn2+ is inward over (1) and outward over (2). The need for more than one transport system inregulating cytoplasmic Ca2+ is discussed."}
{"id": "PMID:8095", "title": "The metal ion catalyzed decomposition of nucleoside diphosphate sugars.", "content": "The metal ion catalysed decomposition of the nucleotide diphosphate sugars, uridine diphosphate glucose, uriding diphosphate galactose, uridine diphosphate N-acetylglucosamine, guanosine diphosphate mannose, and guanosine diphosphate fucose (UDPGlc, UDPGal, UDPGlc-NAc, GDPMan, and GDPFuc, respectively), has been studies as a function of pH. UDPDlc and UDPGal decompose readily to the a,2-cycle phosphate derivative of the sugar and uridine 5'-phosphoric acid (UMP) in the presence of Mn2+. Under all conditions tested, UDPGal decomposes two to three times more rapidly than does UDPGlc. GDPFuc is slowly degraded to free fucose under similar conditions; the other nucleotide diphosphate sugars are stable. The rate of reaction increases with increasing hydroxide ion concentration from pH 6.5 to 7.9 and with metal ion concentration from 10 to 200 mm. Several metal ions are effective catalysts; at pH 7.5 WITH 20 mM UDPGal and 20 mM metal ion, the following apparent first-order rate constants (min-1 x 10(4)) were obtained: Eu3+ 700; Mn2+, 70; Co2+ 27; Zn2+, 22; Ca2+, 3.0; Cu2+, 2.4; and Mg2+, 0. It appears that Mn2+ concentrations that have been used in studies with nucleotide diphosphate sugars at neutral pH can catalyze significant decomposition leading to erroneous interpretation of kinetic and incorporation experiments.", "contents": "The metal ion catalyzed decomposition of nucleoside diphosphate sugars. The metal ion catalysed decomposition of the nucleotide diphosphate sugars, uridine diphosphate glucose, uriding diphosphate galactose, uridine diphosphate N-acetylglucosamine, guanosine diphosphate mannose, and guanosine diphosphate fucose (UDPGlc, UDPGal, UDPGlc-NAc, GDPMan, and GDPFuc, respectively), has been studies as a function of pH. UDPDlc and UDPGal decompose readily to the a,2-cycle phosphate derivative of the sugar and uridine 5'-phosphoric acid (UMP) in the presence of Mn2+. Under all conditions tested, UDPGal decomposes two to three times more rapidly than does UDPGlc. GDPFuc is slowly degraded to free fucose under similar conditions; the other nucleotide diphosphate sugars are stable. The rate of reaction increases with increasing hydroxide ion concentration from pH 6.5 to 7.9 and with metal ion concentration from 10 to 200 mm. Several metal ions are effective catalysts; at pH 7.5 WITH 20 mM UDPGal and 20 mM metal ion, the following apparent first-order rate constants (min-1 x 10(4)) were obtained: Eu3+ 700; Mn2+, 70; Co2+ 27; Zn2+, 22; Ca2+, 3.0; Cu2+, 2.4; and Mg2+, 0. It appears that Mn2+ concentrations that have been used in studies with nucleotide diphosphate sugars at neutral pH can catalyze significant decomposition leading to erroneous interpretation of kinetic and incorporation experiments."}
{"id": "PMID:8096", "title": "The aromatic and heme chromophores of rabbit hemopexin. Difference absorption and fluorescence spectra.", "content": "Spectrophotometric and fluorimetric techniques were employed to charcterize the environment of the heme chromophore of rabbit hemopexin and to monitor changes in the environment of aromatic amino acid residues induced by the interaction of hemopexin with porphyrins and metalloporphyrins. Difference spectra showed maxima at 292 and 285 nm when hemopexin binds heme or deuteroheme but not deuteroporphyrin. These maxima are attributed to alterations in the local environment of tryptophan and tyrosine residues. Spectro-photometric titrations of the tyrosine residues of hemopexin, heme-hemopexin and hemopexin in 8 M urea showed apparent pK values at 11.4, 11.7, and 10.9 respectively. Perturbation difference spectra produced by 20% v/v ethylene glycol are consistent with the exposure of 6-8 of the 14 tyrosine residues and 6-8 of the 15 tryptophan residues of rabbit hemopexin to this perturbant. Only small differences were found between the perturbation spectra of apo- and heme-hemopexin near 290 nm, suggesting that slight or compensating changes in the exposure to solvent of tryptophan chromophores occur. In the Soret spectral region, the exposure of heme in the heme-hemopexin complex to ethylene glycol was 0.7, relative to the fully exposed heme peptide of cytochrome c. The fluorescence quantum yields of rabbit apo- and heme-hemopexin were estimated to be 0.06 and 0.03, respectively, compared to a yield of 0.13 for L-tryptophan. Iodide quenched 50% of the fluorescence of the deuteroheme-hemopexin complex. Cesium was not an effective quencher. Modification of approximately, 4 tryptophan residues with N-bromosuccinimide also decreased the relative fluorescence of apo-hemopexin by 50% and concomitantly reduced the heme-binding ability of the protein by 70%. The existence of sterically unhindered tryptophan residues in either apo- heme-hemopexin is unlikely since no charge transfer compelxes between these proteins and N-methylnicotinamide were detected.", "contents": "The aromatic and heme chromophores of rabbit hemopexin. Difference absorption and fluorescence spectra. Spectrophotometric and fluorimetric techniques were employed to charcterize the environment of the heme chromophore of rabbit hemopexin and to monitor changes in the environment of aromatic amino acid residues induced by the interaction of hemopexin with porphyrins and metalloporphyrins. Difference spectra showed maxima at 292 and 285 nm when hemopexin binds heme or deuteroheme but not deuteroporphyrin. These maxima are attributed to alterations in the local environment of tryptophan and tyrosine residues. Spectro-photometric titrations of the tyrosine residues of hemopexin, heme-hemopexin and hemopexin in 8 M urea showed apparent pK values at 11.4, 11.7, and 10.9 respectively. Perturbation difference spectra produced by 20% v/v ethylene glycol are consistent with the exposure of 6-8 of the 14 tyrosine residues and 6-8 of the 15 tryptophan residues of rabbit hemopexin to this perturbant. Only small differences were found between the perturbation spectra of apo- and heme-hemopexin near 290 nm, suggesting that slight or compensating changes in the exposure to solvent of tryptophan chromophores occur. In the Soret spectral region, the exposure of heme in the heme-hemopexin complex to ethylene glycol was 0.7, relative to the fully exposed heme peptide of cytochrome c. The fluorescence quantum yields of rabbit apo- and heme-hemopexin were estimated to be 0.06 and 0.03, respectively, compared to a yield of 0.13 for L-tryptophan. Iodide quenched 50% of the fluorescence of the deuteroheme-hemopexin complex. Cesium was not an effective quencher. Modification of approximately, 4 tryptophan residues with N-bromosuccinimide also decreased the relative fluorescence of apo-hemopexin by 50% and concomitantly reduced the heme-binding ability of the protein by 70%. The existence of sterically unhindered tryptophan residues in either apo- heme-hemopexin is unlikely since no charge transfer compelxes between these proteins and N-methylnicotinamide were detected."}
{"id": "PMID:8097", "title": "Effect of temperature on tryptophan fluorescence of beta-lactoglobulin B.", "content": "The effect of heat on the conformation of bovine beta-lactoglobulin has been studied using intrinsic fluorescence spectroscopy. Changes in the intensity, wave-length of maximum emission and emission peak width at half height of tryptophan fluorescence over the range 15-90 degrees C at pH 6.4-6.5 has allowed the environments of the two tryptophans in the molecule to be discriminated. At 20 degrees C both tryptophans are in hydrophobic environments. As the temperature is raised the conformation changes such that at about 50 degrees C one of the tryptophans is transferred to a more polar environment accessible to solvent. Conformational changes appear to be reversible if the protein is cooled to 20 degrees C after heat treatments up to 70 degrees C. Above 70 degrees C the second tryptophan residue becomes exposed to solvent. Complete exposure of one residue occurs at 80 degrees C while the other is still partially buried even at 90 degrees C. When the protein is then cooled to 20 degrees C the conformational changes appear to be irreversible with only one tryptophan residue returning to the hydrophobic interior of the molecule.", "contents": "Effect of temperature on tryptophan fluorescence of beta-lactoglobulin B. The effect of heat on the conformation of bovine beta-lactoglobulin has been studied using intrinsic fluorescence spectroscopy. Changes in the intensity, wave-length of maximum emission and emission peak width at half height of tryptophan fluorescence over the range 15-90 degrees C at pH 6.4-6.5 has allowed the environments of the two tryptophans in the molecule to be discriminated. At 20 degrees C both tryptophans are in hydrophobic environments. As the temperature is raised the conformation changes such that at about 50 degrees C one of the tryptophans is transferred to a more polar environment accessible to solvent. Conformational changes appear to be reversible if the protein is cooled to 20 degrees C after heat treatments up to 70 degrees C. Above 70 degrees C the second tryptophan residue becomes exposed to solvent. Complete exposure of one residue occurs at 80 degrees C while the other is still partially buried even at 90 degrees C. When the protein is then cooled to 20 degrees C the conformational changes appear to be irreversible with only one tryptophan residue returning to the hydrophobic interior of the molecule."}
{"id": "PMID:8098", "title": "Structure and fluctuation of a Streptomyces subtilisin inhibitor.", "content": "The kinetics of the hydrogen-deuterium exchange reaction in a subtilisin inhibitor from Streptomyces albogriseolus has been examined by infrared absorption measurement in aqueous solutions at various pH values and temperatures. In the analysis of each piece of kinetic data, it was assumed that the total 104 peptide hydrogen atoms are classified into three kinetic classes A, B1, and B2, and that the sizes of these classes are 72, 15, and 17, respectively at every pH and at every temperature examined. On the basis of the peak position determined for the amide II band in each stage of the exchange reaction, an approximate assignment was suggested of the A, B1 and B2 respectively to an unordered structure, a beta-structure,and an alpha-helical structure in the molecule. This assignment was supported by infrared absorption measurement of a film of this protein and by circular dichroic study of the solutions. On the basis of the temperature effect on the hydrogen-exchange rate constants and on the basis of ultraviolet absorption study in the higher temperature region (40 to 90 degrees C), a discussion has been made on the nature of the fluctuation of the molecular structure of this protein.", "contents": "Structure and fluctuation of a Streptomyces subtilisin inhibitor. The kinetics of the hydrogen-deuterium exchange reaction in a subtilisin inhibitor from Streptomyces albogriseolus has been examined by infrared absorption measurement in aqueous solutions at various pH values and temperatures. In the analysis of each piece of kinetic data, it was assumed that the total 104 peptide hydrogen atoms are classified into three kinetic classes A, B1, and B2, and that the sizes of these classes are 72, 15, and 17, respectively at every pH and at every temperature examined. On the basis of the peak position determined for the amide II band in each stage of the exchange reaction, an approximate assignment was suggested of the A, B1 and B2 respectively to an unordered structure, a beta-structure,and an alpha-helical structure in the molecule. This assignment was supported by infrared absorption measurement of a film of this protein and by circular dichroic study of the solutions. On the basis of the temperature effect on the hydrogen-exchange rate constants and on the basis of ultraviolet absorption study in the higher temperature region (40 to 90 degrees C), a discussion has been made on the nature of the fluctuation of the molecular structure of this protein."}
{"id": "PMID:8099", "title": "Conformation in aqueous medium of the neutral, protonated and anionic forms of 9-beta-D-arabinofuranosyladenine.", "content": "Proton magnetic resonance spectroscopy was employed to study the solution conformations of the neutral, protonated and dissociated forms of the therapeutically active 9-beta-D-arabinofuranosyladenine (araA). In particular, in strongly basic medium, increasing alkalinity led to pronounced changes in chemical shifts and coupling constants of some pentose protons, due to ionization of the pentose hydroxyls, especially the 2'-OH. The neutral form of araA may be characterized as approx. 25% C(2')endo and approx. 60% gauche-gauche, hence somewhat different from that of the therapeutically active 1-beta-D-arabinofuranosylcytosine (araC). By contrast, the conformations of the anionic forms of both of these are identical, predominantly (greater than 80%) C(2')endo and gauche-gauche. With the aid of the 3'-O-methyl derivatives of araA and araC, where only the 2'-OH ionizes, and the accompanying conformational changes are similar, it follows that the conformation C(2')endo and gauche-gauche for all the foregoing is constrained to this form via a strong intramolecular hydrogen bond, viz. O(5')H...O(2')(-). The influence of the foregoing hydrogen bond on the chemical shifts of the adenine H(8) in the araA anion points to the existence of the latter in the form anti. A similar effect of the doubly ionized phosphate group on H(8) in 5'-araAMP shows the nucleotide to also prefer the form anti, as previously demonstrated for 5'-AMP. The conformations of the sugar rings of the neutral forms of araA and adenosine in aqueous medium differ appreciably, whereas in the solid state they are very similar. PMR spectroscopy is shown to be an effective method for following sugar hydroxyl dissociation. The extent of ionization of a given hydroxyl is provided by the resulting chemical shifts of neighbouring (geminal and vicinal) protons. When ionization is accompanied by a change in conformation, the process may be followed also by changes in proton-proton vicinal coupling constants.", "contents": "Conformation in aqueous medium of the neutral, protonated and anionic forms of 9-beta-D-arabinofuranosyladenine. Proton magnetic resonance spectroscopy was employed to study the solution conformations of the neutral, protonated and dissociated forms of the therapeutically active 9-beta-D-arabinofuranosyladenine (araA). In particular, in strongly basic medium, increasing alkalinity led to pronounced changes in chemical shifts and coupling constants of some pentose protons, due to ionization of the pentose hydroxyls, especially the 2'-OH. The neutral form of araA may be characterized as approx. 25% C(2')endo and approx. 60% gauche-gauche, hence somewhat different from that of the therapeutically active 1-beta-D-arabinofuranosylcytosine (araC). By contrast, the conformations of the anionic forms of both of these are identical, predominantly (greater than 80%) C(2')endo and gauche-gauche. With the aid of the 3'-O-methyl derivatives of araA and araC, where only the 2'-OH ionizes, and the accompanying conformational changes are similar, it follows that the conformation C(2')endo and gauche-gauche for all the foregoing is constrained to this form via a strong intramolecular hydrogen bond, viz. O(5')H...O(2')(-). The influence of the foregoing hydrogen bond on the chemical shifts of the adenine H(8) in the araA anion points to the existence of the latter in the form anti. A similar effect of the doubly ionized phosphate group on H(8) in 5'-araAMP shows the nucleotide to also prefer the form anti, as previously demonstrated for 5'-AMP. The conformations of the sugar rings of the neutral forms of araA and adenosine in aqueous medium differ appreciably, whereas in the solid state they are very similar. PMR spectroscopy is shown to be an effective method for following sugar hydroxyl dissociation. The extent of ionization of a given hydroxyl is provided by the resulting chemical shifts of neighbouring (geminal and vicinal) protons. When ionization is accompanied by a change in conformation, the process may be followed also by changes in proton-proton vicinal coupling constants."}
{"id": "PMID:8100", "title": "Regulation of nitrogen fixation by Rhizobia. Export of fixed N2 as NH+4.", "content": "The metabolic fate of gaseous nitrogen (15N2) fixed by free-living cultures of Rhizobia (root nodule bacteria) induced for their N2-fixation system was followed. A majority of the fixed 15N2 was found to be exported into the cell supernatant. For example, as much as 94% of the 15N2 fixed by Rhizobium japonicum (soybean symbiont) was recovered as 15NH+4 from the cell supernatant following alkaline diffusion. Several species of root nodule bacteria also exported large quantities of NH+4 from L-histidine. Evidence is presented that overproduction and export of NH+4 by free-living Rhizobia may be closely linked to the control of several key enzymes of NH+4 assimilation. For instance, NH+4 was found to repress glutamine synthetase whereas L-glutamate repressed glutamate synthase. Assimilation of NH+4 as nitrogen source for growth of Rhizobia was inhibited by glutamate. The mechanism of regulation of NH+4 production by root nodule bacteria is discussed.", "contents": "Regulation of nitrogen fixation by Rhizobia. Export of fixed N2 as NH+4. The metabolic fate of gaseous nitrogen (15N2) fixed by free-living cultures of Rhizobia (root nodule bacteria) induced for their N2-fixation system was followed. A majority of the fixed 15N2 was found to be exported into the cell supernatant. For example, as much as 94% of the 15N2 fixed by Rhizobium japonicum (soybean symbiont) was recovered as 15NH+4 from the cell supernatant following alkaline diffusion. Several species of root nodule bacteria also exported large quantities of NH+4 from L-histidine. Evidence is presented that overproduction and export of NH+4 by free-living Rhizobia may be closely linked to the control of several key enzymes of NH+4 assimilation. For instance, NH+4 was found to repress glutamine synthetase whereas L-glutamate repressed glutamate synthase. Assimilation of NH+4 as nitrogen source for growth of Rhizobia was inhibited by glutamate. The mechanism of regulation of NH+4 production by root nodule bacteria is discussed."}
{"id": "PMID:8101", "title": "Amino acids as repressors of nitrogenase biosynthesis in Klebsiella pneumoniae.", "content": "Nitrogenase biosynthesis in Klebsiella pneumoniae including mutant strains, which produce nitrogenase in the presence of NH+4 (Shanmugam, K.T., Chan, Irene, and Morandi, C. (1975) Biochim. Biophys. Acta 408, 101--111) is repressed by a mixture of L-amino acids. Biochemical analysis shows that glutamine synthetase activity in strains SK-24, SK-28, and SK-29 is also repressed by amino acids, with no detectable effect on glutamate dehydrogenase. Among the various amino acids, L-glutamine in combination with L-aspartate was found to repress nitrogenase biosynthesis completely. In the presence of high concentrations of glutamine (1 mg/ml) even NH+4 repressed nitrogenase biosynthesis in the strains SK-27, SK-37, SK-55 and SK-56. Under these conditions, increased glutamate dehydrogenase activity was also detected. Physiological studies show that nitrogenase derepressed strains are unable to utilize NH+4 as sole source of nitrogen for biosynthesis of glutamate for biosynthesis of glutamate, whereas back mutations leading to NH+4 utilization results in sensitivity to repression by NH+4. These findings suggest that amino acids play an important role as regulators of nitrogen fixation.", "contents": "Amino acids as repressors of nitrogenase biosynthesis in Klebsiella pneumoniae. Nitrogenase biosynthesis in Klebsiella pneumoniae including mutant strains, which produce nitrogenase in the presence of NH+4 (Shanmugam, K.T., Chan, Irene, and Morandi, C. (1975) Biochim. Biophys. Acta 408, 101--111) is repressed by a mixture of L-amino acids. Biochemical analysis shows that glutamine synthetase activity in strains SK-24, SK-28, and SK-29 is also repressed by amino acids, with no detectable effect on glutamate dehydrogenase. Among the various amino acids, L-glutamine in combination with L-aspartate was found to repress nitrogenase biosynthesis completely. In the presence of high concentrations of glutamine (1 mg/ml) even NH+4 repressed nitrogenase biosynthesis in the strains SK-27, SK-37, SK-55 and SK-56. Under these conditions, increased glutamate dehydrogenase activity was also detected. Physiological studies show that nitrogenase derepressed strains are unable to utilize NH+4 as sole source of nitrogen for biosynthesis of glutamate for biosynthesis of glutamate, whereas back mutations leading to NH+4 utilization results in sensitivity to repression by NH+4. These findings suggest that amino acids play an important role as regulators of nitrogen fixation."}
{"id": "PMID:8102", "title": "Mechanism of inhibition of Chromatium D growth by L-methionine. Regulation of L-threonine biosynthesis by the intracellular level of S-adenosylmethionine.", "content": "(1) An unusual accumulation of S-adenosyl-L-methionine in Chromatium D was associated with a marked growth inhibition by L-methionine. The inhibition was overcome by L-isoleucine, L-leucine, L-phyenylalanine, L-threonine, L-valine and putrescien. Based on their effects, these compounds are classified into 3 types. (2) L-Isoleucine, L-leucine, L-phyenylalanine and L-valine (Type I) inhibited the L-methionine uptake and consequently prevented the bacterium from the unusual accumulation of S-adenosyl-L-methionine even in the presence of L-methionine in the medium. Putrescine (Type II) stimulated the consumption of S-adenosyl-L-methionine, but did not influence the L-methionine uptake. Hence, the effect of putrescine would be explained by the action to diminish the intracellular level of S-adenosyl-L-methionine. L-Threonine (Type III) neither inhibited the L-methionine uptake nor affected the content of S-adenoxyl-L-methionine due to the addition of L-methionine. (3) The specific activity of homoserine kinase (EC 2.7.1.39) was greatly lowered by the addition of L-methionine under conditions in which Chromatium D unusually accumulates S-adenoxyl-L-methionine. Homoserine dehydrogenase (EC 1.1.1.3) activity was inhbitied by S-adenosyl-L-methionine (50% inhibition index, 3.5 mM). These facts strongly suggest that the growth inhibition by L-methionine is associated with the L-threonine deficiency caused by the unusual accumulation of S-adenosyl-L-methionine.", "contents": "Mechanism of inhibition of Chromatium D growth by L-methionine. Regulation of L-threonine biosynthesis by the intracellular level of S-adenosylmethionine. (1) An unusual accumulation of S-adenosyl-L-methionine in Chromatium D was associated with a marked growth inhibition by L-methionine. The inhibition was overcome by L-isoleucine, L-leucine, L-phyenylalanine, L-threonine, L-valine and putrescien. Based on their effects, these compounds are classified into 3 types. (2) L-Isoleucine, L-leucine, L-phyenylalanine and L-valine (Type I) inhibited the L-methionine uptake and consequently prevented the bacterium from the unusual accumulation of S-adenosyl-L-methionine even in the presence of L-methionine in the medium. Putrescine (Type II) stimulated the consumption of S-adenosyl-L-methionine, but did not influence the L-methionine uptake. Hence, the effect of putrescine would be explained by the action to diminish the intracellular level of S-adenosyl-L-methionine. L-Threonine (Type III) neither inhibited the L-methionine uptake nor affected the content of S-adenoxyl-L-methionine due to the addition of L-methionine. (3) The specific activity of homoserine kinase (EC 2.7.1.39) was greatly lowered by the addition of L-methionine under conditions in which Chromatium D unusually accumulates S-adenoxyl-L-methionine. Homoserine dehydrogenase (EC 1.1.1.3) activity was inhbitied by S-adenosyl-L-methionine (50% inhibition index, 3.5 mM). These facts strongly suggest that the growth inhibition by L-methionine is associated with the L-threonine deficiency caused by the unusual accumulation of S-adenosyl-L-methionine."}
{"id": "PMID:8103", "title": "The ionic control of 1,25-dihydroxyvitamin D-3 synthesis in isolated chick renal mitochondria. The role of potassium.", "content": "In previous studies it was found that change in the concentrations of Ca2+, H+, and HPO2-4 in the incubation medium altered the rates of synthesis of 1,25-dihydroxyvitamin D-3 (1,25(OH)2D-3) by isolated renal mitochondria obtained from D-deficient chicks. The present studies demonstrate that raising the medium concentration of K+ from 1 to 50 mM leads to a 6-fold increase in rate of 1,25(OH)2D-3 synthesis by isolated chick mitochondria; that the magnitnitude of this K+-dependent stimulation is enhaced by optimal concentrations of calcium (pCa = 5) and phosphate (pPi = 3) (3 mM) but not by pH (from 6.8 to 7.4); that the effect is not produced by similar changes in media Na+ concentration; and that the stimulatory effect of K+ is not blocked by ruthenium red, and inhibitor of calcium transport and of the calcium-dependent stimulation of mitochondrial 1,25(OH) 2D-3 synthesis. It was also found that valinomycin, a K+-specific ionophore, enhanced the sensitivity of the mitochondrial 1 alpha-hydroxylase activity to K+. In the presence of valinomycin, an increase of pK+ to 3 was sufficient to cause a significant stimulation of 1,25(OH)2D-3 synthesis. It was concluded that changes in the ion content of the mitochondrial matrix space regulated the activity of the 1 alpha-hydroxylase.", "contents": "The ionic control of 1,25-dihydroxyvitamin D-3 synthesis in isolated chick renal mitochondria. The role of potassium. In previous studies it was found that change in the concentrations of Ca2+, H+, and HPO2-4 in the incubation medium altered the rates of synthesis of 1,25-dihydroxyvitamin D-3 (1,25(OH)2D-3) by isolated renal mitochondria obtained from D-deficient chicks. The present studies demonstrate that raising the medium concentration of K+ from 1 to 50 mM leads to a 6-fold increase in rate of 1,25(OH)2D-3 synthesis by isolated chick mitochondria; that the magnitnitude of this K+-dependent stimulation is enhaced by optimal concentrations of calcium (pCa = 5) and phosphate (pPi = 3) (3 mM) but not by pH (from 6.8 to 7.4); that the effect is not produced by similar changes in media Na+ concentration; and that the stimulatory effect of K+ is not blocked by ruthenium red, and inhibitor of calcium transport and of the calcium-dependent stimulation of mitochondrial 1,25(OH) 2D-3 synthesis. It was also found that valinomycin, a K+-specific ionophore, enhanced the sensitivity of the mitochondrial 1 alpha-hydroxylase activity to K+. In the presence of valinomycin, an increase of pK+ to 3 was sufficient to cause a significant stimulation of 1,25(OH)2D-3 synthesis. It was concluded that changes in the ion content of the mitochondrial matrix space regulated the activity of the 1 alpha-hydroxylase."}
{"id": "PMID:8104", "title": "Properties of mouse alpha-galactosidase.", "content": "alpha-Galactosidase has been examined in various murine tissues using the substrate 4-methylumbelliferyl-alpha-galactoside. Mouse liver appears to contain a single major form of the enzyme, as judged by chromatography and electrophoresis. The enzmye was purified 467-fold with a yield of about 40% by a method involving chromatography on Concanavalin A-Sepharose. It has maximal activity at pH 4.2, a Km value of 1.4 mM, and energy of activation of 16 400 cal/mol, and a molecular weight of 150 000 at pH 5.2. It is inhibited at high concentrations of myoinositol and appears to contain N-acetylneuraminic acid. In these characteristics it resembles human alpha-galactosidase A. The enzyme from various tissues differs in electrophoretic mobility. After treatment with neuraminidase, however, the enzyme from all tissues comigrates as a single band of activity. By this criterion the alpha-galactosidase of liver is most heavily sialylated and that from kidney the least. As estimated by gel filtration, the enzyme from liver and kidney exists as species of molecular weight 320 000, 150 000 and 70 000, depending upon pH and ionic strength. This appears to be the result of aggregation of the enzyme, since the forms are interconvertible and under some conditions a single molecular weight species is observed. The liver enzyme is primarily lysosomal, while the kidney enzyme is distributed approximately equally between lysosomal and microsomal fractions.", "contents": "Properties of mouse alpha-galactosidase. alpha-Galactosidase has been examined in various murine tissues using the substrate 4-methylumbelliferyl-alpha-galactoside. Mouse liver appears to contain a single major form of the enzyme, as judged by chromatography and electrophoresis. The enzmye was purified 467-fold with a yield of about 40% by a method involving chromatography on Concanavalin A-Sepharose. It has maximal activity at pH 4.2, a Km value of 1.4 mM, and energy of activation of 16 400 cal/mol, and a molecular weight of 150 000 at pH 5.2. It is inhibited at high concentrations of myoinositol and appears to contain N-acetylneuraminic acid. In these characteristics it resembles human alpha-galactosidase A. The enzyme from various tissues differs in electrophoretic mobility. After treatment with neuraminidase, however, the enzyme from all tissues comigrates as a single band of activity. By this criterion the alpha-galactosidase of liver is most heavily sialylated and that from kidney the least. As estimated by gel filtration, the enzyme from liver and kidney exists as species of molecular weight 320 000, 150 000 and 70 000, depending upon pH and ionic strength. This appears to be the result of aggregation of the enzyme, since the forms are interconvertible and under some conditions a single molecular weight species is observed. The liver enzyme is primarily lysosomal, while the kidney enzyme is distributed approximately equally between lysosomal and microsomal fractions."}
{"id": "PMID:8105", "title": "Insulin and glucagon degradation by the kidney. I. Subcellular distribution under different assay condition.", "content": "Insulin and glucagon degradation by rat kidney homogenates and subcellular fractions was examined under a variety of conditions including high and low substrate concentrations, at pH 4 and pH 7, with and without glutathione. At high insulin concentration (4.1 - 10(-5) M) insulin degradation by the homogenate was greatest at pH 4 but at low insulin concentration (1 - 10(-10) M) insulin degradation was greatest at pH 7. At either high or low glucagon concentration glucagon degradation by the homogenate was greatest at pH 7. Glutathione at pH 7 stimulated insulin degradation at high insulin concentrations and inhibited insulin degradation at low concentrations; Glucagon degradation at pH 7 was inhibited at both high and low concentrations of glucagon by glutathionemseparation of kidney into cortex and medulla prior to homogenation produced a pattern of insulin and glucagon degradation identical to the whole homogenate but glucagon degradation by the medulla was greater than by the cortex. Examination of degradation by subcellular fractions revealed that at high concentration at neutral pH most insulin was degraded by the 100 000 X g pellet but at low insulin concentrations over 90% of the activity was in the 100 000 X g supernatant; At pH 7, at both high and low concentrations, most glucagon-degrading activity was in the 100 000 X g pellet, although the cytosol also had activity; At pH 4 most degradation occurred in the lysosomal fractions. Separation into cortex and medulla again showed similar distribution of activity as the whole gland with the medulla having more glucagon-degrading activity than the cortex. With low insulin concentrations the cortex 100 000 X g supernatant had higher relative specific activities than the medulla supernatant. Examination of recoveries of enzyme activity revealed that the subcellular fractions consistently had markedly less insulin-degrading activity than the original homogenate. This loss of activity was only discernible when insulin degradation was performed at pH 7 at low substrate concentrations. Comparable losses of glucagon-degrading activity were not seen.", "contents": "Insulin and glucagon degradation by the kidney. I. Subcellular distribution under different assay condition. Insulin and glucagon degradation by rat kidney homogenates and subcellular fractions was examined under a variety of conditions including high and low substrate concentrations, at pH 4 and pH 7, with and without glutathione. At high insulin concentration (4.1 - 10(-5) M) insulin degradation by the homogenate was greatest at pH 4 but at low insulin concentration (1 - 10(-10) M) insulin degradation was greatest at pH 7. At either high or low glucagon concentration glucagon degradation by the homogenate was greatest at pH 7. Glutathione at pH 7 stimulated insulin degradation at high insulin concentrations and inhibited insulin degradation at low concentrations; Glucagon degradation at pH 7 was inhibited at both high and low concentrations of glucagon by glutathionemseparation of kidney into cortex and medulla prior to homogenation produced a pattern of insulin and glucagon degradation identical to the whole homogenate but glucagon degradation by the medulla was greater than by the cortex. Examination of degradation by subcellular fractions revealed that at high concentration at neutral pH most insulin was degraded by the 100 000 X g pellet but at low insulin concentrations over 90% of the activity was in the 100 000 X g supernatant; At pH 7, at both high and low concentrations, most glucagon-degrading activity was in the 100 000 X g pellet, although the cytosol also had activity; At pH 4 most degradation occurred in the lysosomal fractions. Separation into cortex and medulla again showed similar distribution of activity as the whole gland with the medulla having more glucagon-degrading activity than the cortex. With low insulin concentrations the cortex 100 000 X g supernatant had higher relative specific activities than the medulla supernatant. Examination of recoveries of enzyme activity revealed that the subcellular fractions consistently had markedly less insulin-degrading activity than the original homogenate. This loss of activity was only discernible when insulin degradation was performed at pH 7 at low substrate concentrations. Comparable losses of glucagon-degrading activity were not seen."}
{"id": "PMID:8106", "title": "Insulin and glucagon degradation by the kidney. II. Characterization of the mechanisms at neutral pH.", "content": "Examination of insulin and glucagon degradation by rat kidney subcellular fractions revealed that most degrading activity was localized to the 100 000 X g pellet and 100 000 X g supernatant fractions. Further characterization of the degrading activities of the 100 000 X g pellet and supernatant suggested that three types of enzymatic activity were present at neutral pH. From the cytosol an enzyme with characteristics of the insulin glucagon protease of skeletal muscle was purified. This enzyme appeared to be responsible for insulin degradation by the kidney at physiological insulin concentrations. This enzyme also contributed to glucagon degradation but was not the most active mechanism for this. In the 100 000 X g pellet at least two separate enzymatic activities were present. One of these had properties consistent with those described for glutathione insulin transhydrogenase and appeared to be responsible for insulin degradation at high insulin concentration. The other enzyme was associated with the brush border and had properties consistent with the brush border neutral protease. This enzyme appeared responsible for glucagon degradation at both low and high substrate concentrations. An apparent marked synergism between the 100 000 X g pellet and the 100 000 X g supernatant was noted for insulin degradation at physiological insulin concentrations. Pellet glucagon-degrading activity and soluble insulin-degrading activity were necessary for this. The mechanism was found to be limited insulin degradation by the soluble enzyme resulting in both trichloroacetic acid-precipitable trichloroacetic acid-soluble fragments followed by further degradtion of the fragments by the glucagon-degrading enzyme resulting in an additional increase in trichloroacetic acid-soluble products.", "contents": "Insulin and glucagon degradation by the kidney. II. Characterization of the mechanisms at neutral pH. Examination of insulin and glucagon degradation by rat kidney subcellular fractions revealed that most degrading activity was localized to the 100 000 X g pellet and 100 000 X g supernatant fractions. Further characterization of the degrading activities of the 100 000 X g pellet and supernatant suggested that three types of enzymatic activity were present at neutral pH. From the cytosol an enzyme with characteristics of the insulin glucagon protease of skeletal muscle was purified. This enzyme appeared to be responsible for insulin degradation by the kidney at physiological insulin concentrations. This enzyme also contributed to glucagon degradation but was not the most active mechanism for this. In the 100 000 X g pellet at least two separate enzymatic activities were present. One of these had properties consistent with those described for glutathione insulin transhydrogenase and appeared to be responsible for insulin degradation at high insulin concentration. The other enzyme was associated with the brush border and had properties consistent with the brush border neutral protease. This enzyme appeared responsible for glucagon degradation at both low and high substrate concentrations. An apparent marked synergism between the 100 000 X g pellet and the 100 000 X g supernatant was noted for insulin degradation at physiological insulin concentrations. Pellet glucagon-degrading activity and soluble insulin-degrading activity were necessary for this. The mechanism was found to be limited insulin degradation by the soluble enzyme resulting in both trichloroacetic acid-precipitable trichloroacetic acid-soluble fragments followed by further degradtion of the fragments by the glucagon-degrading enzyme resulting in an additional increase in trichloroacetic acid-soluble products."}
{"id": "PMID:8107", "title": "Human pancreatic-type ribonucleases with activity against double-stranded ribonucleic acids.", "content": "Purified acid-thermostable ribonuclease (Ribonucleate 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22) from human pancreas degrades double-stranded RNA at 2% the rate for single-stranded RNA. The activities against single-stranded RNA and double-stranded RNA were shown to be due to a single enzyme with properties similar to bovine pancreatic RNAase A. For purposes of comparison the activities against double-stranded RNA of crystalline ribonucleases of the whale, rat and cow were assayed and found to be 0.4%, 0.03% and 0.003%, respectively, of their activities against single-stranded RNA. Both human serum and urine contain RNAse components of pancreatic origin which hydrolyze double-stranded RNA at 2% and 0.4%, respectively, of the rates against single-stranded RNA. By contrast, purified acid-thermostable RNAases from human spleen and liver hydrlyze double-stranded RNA at least 20-fold more slowly than human pancreatic RNAase, relative to the corresponding rates against single-stranded RNA. The human pancreatic and serum enzymes exhibit appreciable activity against the poly(C) component of the double-stranded poly(I)-poly(C); they also attack poly(C) itself at approximately 25 times the rate for poly(U) and at more than 50 times the rate for single-stranded RNA.", "contents": "Human pancreatic-type ribonucleases with activity against double-stranded ribonucleic acids. Purified acid-thermostable ribonuclease (Ribonucleate 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22) from human pancreas degrades double-stranded RNA at 2% the rate for single-stranded RNA. The activities against single-stranded RNA and double-stranded RNA were shown to be due to a single enzyme with properties similar to bovine pancreatic RNAase A. For purposes of comparison the activities against double-stranded RNA of crystalline ribonucleases of the whale, rat and cow were assayed and found to be 0.4%, 0.03% and 0.003%, respectively, of their activities against single-stranded RNA. Both human serum and urine contain RNAse components of pancreatic origin which hydrolyze double-stranded RNA at 2% and 0.4%, respectively, of the rates against single-stranded RNA. By contrast, purified acid-thermostable RNAases from human spleen and liver hydrlyze double-stranded RNA at least 20-fold more slowly than human pancreatic RNAase, relative to the corresponding rates against single-stranded RNA. The human pancreatic and serum enzymes exhibit appreciable activity against the poly(C) component of the double-stranded poly(I)-poly(C); they also attack poly(C) itself at approximately 25 times the rate for poly(U) and at more than 50 times the rate for single-stranded RNA."}
{"id": "PMID:8108", "title": "Purification and characterization of rat liver microsomal beta-glucuronidase.", "content": "Beta-Glucuronidase (EC 3.2.1.31) has been isolated from rat-liver microsomes by a novel chromatographic method employing antibody to rat preputial gland beta-glucuronidase coupled to Sepharose. The purified enzyme, homogeneous by several methods, was purified some 1700-fold. The microsomal beta-glucuronidase has been characterized with respect to catalysis, stability, and molecular weight. The purified enzyme is a tetramer of 290 000 daltons. Comparative studies with lysosomal beta-glucuronidase indicate that while these two enzymes are electrophoretically distinct, they are catalytically and immunologically identical and have indistinguishable molecular dimensions. The results suggest that microsomal and lysosomal beta-glucuronidase are charge isomers.", "contents": "Purification and characterization of rat liver microsomal beta-glucuronidase. Beta-Glucuronidase (EC 3.2.1.31) has been isolated from rat-liver microsomes by a novel chromatographic method employing antibody to rat preputial gland beta-glucuronidase coupled to Sepharose. The purified enzyme, homogeneous by several methods, was purified some 1700-fold. The microsomal beta-glucuronidase has been characterized with respect to catalysis, stability, and molecular weight. The purified enzyme is a tetramer of 290 000 daltons. Comparative studies with lysosomal beta-glucuronidase indicate that while these two enzymes are electrophoretically distinct, they are catalytically and immunologically identical and have indistinguishable molecular dimensions. The results suggest that microsomal and lysosomal beta-glucuronidase are charge isomers."}
{"id": "PMID:8109", "title": "Purification and some properties of a neutral protease from human leukocyte granules and its comparison with pancreatic elastase.", "content": "1. A cationic protease has been purified from the granule fraction of blood-donor leukocytes by a preparative method including precipitation by acetone and chromatography on Bio-Gel A 1.5 m, CM-Sephadex C-50 and Sephadex G-G-75. 2. The pH optimum against denatured bovine hemoglobin is 7.4. Gel chromatography indicated a molecular weight close to 23 000. 3. This neutral protease (EC 3.4.-.-) is able to split the synthetic esters Z-Ala-NPh and AcAla3OMe, its activity on the former substrate being 2.2 times greater than that of pancreatic elastase, on the latter the same. It differs crucially from pancreatic elastase in having small elastinolytic activity. 4. In cationic disk electrophoresis, neutral protease resolves into three protein bands with lower mobility than lysozyme: all bands exhibit esterolytic activity against 2-acetoxy-3-naphthoic acid o-toluidide, strongly suggesting that they represent isoenzymes. 5. The enzyme is completely inhibited by iPr2P-F, partially so by soybean trypsin inhibitor and Trasylol. Cysteine, EDTA and TosLysCH2Cl have no effect. 6. During chromatography on CM-Sephadex C-50 a more positively charged enzyme(s) was identified. This had hemoglobinolytic activity at pH 7.4 but only a small esterolytic effect on Z-Ala-NPh; it showed only traces of activity against AcAla3OMe.", "contents": "Purification and some properties of a neutral protease from human leukocyte granules and its comparison with pancreatic elastase. 1. A cationic protease has been purified from the granule fraction of blood-donor leukocytes by a preparative method including precipitation by acetone and chromatography on Bio-Gel A 1.5 m, CM-Sephadex C-50 and Sephadex G-G-75. 2. The pH optimum against denatured bovine hemoglobin is 7.4. Gel chromatography indicated a molecular weight close to 23 000. 3. This neutral protease (EC 3.4.-.-) is able to split the synthetic esters Z-Ala-NPh and AcAla3OMe, its activity on the former substrate being 2.2 times greater than that of pancreatic elastase, on the latter the same. It differs crucially from pancreatic elastase in having small elastinolytic activity. 4. In cationic disk electrophoresis, neutral protease resolves into three protein bands with lower mobility than lysozyme: all bands exhibit esterolytic activity against 2-acetoxy-3-naphthoic acid o-toluidide, strongly suggesting that they represent isoenzymes. 5. The enzyme is completely inhibited by iPr2P-F, partially so by soybean trypsin inhibitor and Trasylol. Cysteine, EDTA and TosLysCH2Cl have no effect. 6. During chromatography on CM-Sephadex C-50 a more positively charged enzyme(s) was identified. This had hemoglobinolytic activity at pH 7.4 but only a small esterolytic effect on Z-Ala-NPh; it showed only traces of activity against AcAla3OMe."}
{"id": "PMID:8110", "title": "Novel activity of potato nucleotide pyrophosphatase.", "content": "The classical Kornberger-Pricer procedure for purification of potato nucleotide pyrophosphatase (EC 3.6.1.9) has been modified to yield a preparation purified 2500-fold. In addition to the known activity against pyrophosphate linkages in pyrophosphates located at the 5'-OH of nucleosides, and phosphodiester linkages in aryl esters of nucleoside-5'-phosphates, the enzyme has now been shown to catalyze the cleavage of: (a) aryl esters of nucleoside-3'-phosphates and orthophosphates, (b) nucleotide pyrophosphate linkages of the type (3')-pp-(3'), and (c) pm7G from m7GpppGm-terminated fragments of viral mRNA. Activities against aryl esters of nucleoside-3'- and 5'-phosphates, and NAD, were shown to be due to the same protein by three criteria: (a) constant ratio of activities during purification and gel electrophoresis, (b) identical chromatographic properties in various systems, and (c) similarities in pH-dependence, heat inactivation, and the effects of cations and other substances. Since potato nucleotide pyrophosphatase does not exhibit exonuclease or phosphatase activities against natural substrates for the latter enzymes, but does cleave synthetic aryl esters of nucleotide-3'- and 5'-phosphates and of orthophosphate, it follows that these substrates are not suitable for detection of such activities in higher plants.", "contents": "Novel activity of potato nucleotide pyrophosphatase. The classical Kornberger-Pricer procedure for purification of potato nucleotide pyrophosphatase (EC 3.6.1.9) has been modified to yield a preparation purified 2500-fold. In addition to the known activity against pyrophosphate linkages in pyrophosphates located at the 5'-OH of nucleosides, and phosphodiester linkages in aryl esters of nucleoside-5'-phosphates, the enzyme has now been shown to catalyze the cleavage of: (a) aryl esters of nucleoside-3'-phosphates and orthophosphates, (b) nucleotide pyrophosphate linkages of the type (3')-pp-(3'), and (c) pm7G from m7GpppGm-terminated fragments of viral mRNA. Activities against aryl esters of nucleoside-3'- and 5'-phosphates, and NAD, were shown to be due to the same protein by three criteria: (a) constant ratio of activities during purification and gel electrophoresis, (b) identical chromatographic properties in various systems, and (c) similarities in pH-dependence, heat inactivation, and the effects of cations and other substances. Since potato nucleotide pyrophosphatase does not exhibit exonuclease or phosphatase activities against natural substrates for the latter enzymes, but does cleave synthetic aryl esters of nucleotide-3'- and 5'-phosphates and of orthophosphate, it follows that these substrates are not suitable for detection of such activities in higher plants."}
{"id": "PMID:8111", "title": "Urea amidolyase of Candida utilis. Characterization of the urea cleavage reactions.", "content": "Evidence is presented that the enzymes catalyzing the three reactions involved in urea cleavage in Candida utilis, biotin carboxylation, urea carboxylation, and allophanate hydrolysis occur as a complex of enzymes. The allophanate-hydrolyzing activity could not be separated from the urea-cleaving activity using common methods of protein purification. Further, urea cleavage and allophanate hydrolysis activities are induced coordinately in cells grown on various nitrogen sources. The reactions involved in urea cleavage can be distinguished from one another on the basis of their sensitivities to (a) heat, (b) pH, and (c) chemical inhibitors. Evidence is presented for the product of the first reaction in urea cleavage, biotin carboxylation. Production of carboxylated enzyme is ATP dependent and avidin sensitive. Carboxylated enzyme is not observed in the presence of 1 mM urea.", "contents": "Urea amidolyase of Candida utilis. Characterization of the urea cleavage reactions. Evidence is presented that the enzymes catalyzing the three reactions involved in urea cleavage in Candida utilis, biotin carboxylation, urea carboxylation, and allophanate hydrolysis occur as a complex of enzymes. The allophanate-hydrolyzing activity could not be separated from the urea-cleaving activity using common methods of protein purification. Further, urea cleavage and allophanate hydrolysis activities are induced coordinately in cells grown on various nitrogen sources. The reactions involved in urea cleavage can be distinguished from one another on the basis of their sensitivities to (a) heat, (b) pH, and (c) chemical inhibitors. Evidence is presented for the product of the first reaction in urea cleavage, biotin carboxylation. Production of carboxylated enzyme is ATP dependent and avidin sensitive. Carboxylated enzyme is not observed in the presence of 1 mM urea."}
{"id": "PMID:8112", "title": "Purification and characterization of the fibrinolytic principle of Agkistrodon acutus venom.", "content": "By means of DEAE-Sephadex A-50 column chromatography, Agkistrodon acutus venom was separated into twelve fractions. The fibrinolytic activity was concentrated in Fraction 9. This fraction was rechromatographed on Sephadex G-75 three times and a single peak was obtained. The patterns of microzone and disc electrophoresis also showed a single band. A single, symmetrical boundary with a value of 2.44 S was obtained by ultracentrifugation, the molecular weight of which was estimated to be 24 100, and the isoelectric point 3.8. The specific activity was four times higher than that of crude venom. The optimal pH value on fibrinolysis was 7.4. In addition to fibrinolytic activity, the purified principle also had fibrinogenolytic and caseinolytic activities. The purified fibrinolytic principle had a specific action on the a(A) chain subunit of fibrinogen, leaving the beta(B) chain and the gamma chain unaffected.", "contents": "Purification and characterization of the fibrinolytic principle of Agkistrodon acutus venom. By means of DEAE-Sephadex A-50 column chromatography, Agkistrodon acutus venom was separated into twelve fractions. The fibrinolytic activity was concentrated in Fraction 9. This fraction was rechromatographed on Sephadex G-75 three times and a single peak was obtained. The patterns of microzone and disc electrophoresis also showed a single band. A single, symmetrical boundary with a value of 2.44 S was obtained by ultracentrifugation, the molecular weight of which was estimated to be 24 100, and the isoelectric point 3.8. The specific activity was four times higher than that of crude venom. The optimal pH value on fibrinolysis was 7.4. In addition to fibrinolytic activity, the purified principle also had fibrinogenolytic and caseinolytic activities. The purified fibrinolytic principle had a specific action on the a(A) chain subunit of fibrinogen, leaving the beta(B) chain and the gamma chain unaffected."}
{"id": "PMID:8113", "title": "Specific fluorescent derivatives of macromolecules. Reaction of dansyl fluoride with serine proteinases.", "content": "5-Dimethylaminonaphthalene-1-sulfonyl fluoride was evaluated as a reagent for the selective labeling of proteins. In a comparative study with Dns-chloride a greatly increased selectivity of the fluoride was found with a number of proteins. The reaction of Dns-fluoride with alpha-chymotrypsin, subtilisin Carlsberg and trypsin was found to be highly specific, resulting in a stoichiometric incorporation of the Dns label with concomitant loss of enzymatic activity. The reaction of Dns-chloride with the same proteinases is unspecific. Evidence was obtained to indicate that reaction of the serine esterases with Dns-fluoride occurs exclusively at the active serine residue. The stability of Dns-fluoride labeled chymotrypsin was investigated. The conjugate was found to be fairly stable in the pH range from 3 to 9 at 25 degrees C and is therefore suitable for fluorescence investigations of the chymotrypsin active-site. Molar extinction coefficients for Dns-labeled serine proteinases were determined using radiocative label.", "contents": "Specific fluorescent derivatives of macromolecules. Reaction of dansyl fluoride with serine proteinases. 5-Dimethylaminonaphthalene-1-sulfonyl fluoride was evaluated as a reagent for the selective labeling of proteins. In a comparative study with Dns-chloride a greatly increased selectivity of the fluoride was found with a number of proteins. The reaction of Dns-fluoride with alpha-chymotrypsin, subtilisin Carlsberg and trypsin was found to be highly specific, resulting in a stoichiometric incorporation of the Dns label with concomitant loss of enzymatic activity. The reaction of Dns-chloride with the same proteinases is unspecific. Evidence was obtained to indicate that reaction of the serine esterases with Dns-fluoride occurs exclusively at the active serine residue. The stability of Dns-fluoride labeled chymotrypsin was investigated. The conjugate was found to be fairly stable in the pH range from 3 to 9 at 25 degrees C and is therefore suitable for fluorescence investigations of the chymotrypsin active-site. Molar extinction coefficients for Dns-labeled serine proteinases were determined using radiocative label."}
{"id": "PMID:8114", "title": "Hemoglobin Athens-Georgia, or alpha 2 beta 2 40(C6)Arg replaced by Lys, a hemoglobin variant with an increased oxygen affinity.", "content": "A new hemoglobin variant, termed hemoglobin Athens-Georgia, has been found in a 23-year-old Caucasian student and three members of her family. The electrophoretic mobility of this variant at pH 9.0 is slightly less than that of hemoglobin-A. Arginyl residue in position 40 of the beta chain, corresponding to position 6 of the C helix, has been replaced by a lysyl residue. This amino acid substitution is at the alpha1-beta2 contact and slightly affects the oxygen binding properties of the hemoglobin molecule. Hemoglobin Athens-Georgia has an increased affinity for oxygen, a normal heme-heme interaction and a normal Bohr effect. Hematological abnormalities are not associated with this variant.", "contents": "Hemoglobin Athens-Georgia, or alpha 2 beta 2 40(C6)Arg replaced by Lys, a hemoglobin variant with an increased oxygen affinity. A new hemoglobin variant, termed hemoglobin Athens-Georgia, has been found in a 23-year-old Caucasian student and three members of her family. The electrophoretic mobility of this variant at pH 9.0 is slightly less than that of hemoglobin-A. Arginyl residue in position 40 of the beta chain, corresponding to position 6 of the C helix, has been replaced by a lysyl residue. This amino acid substitution is at the alpha1-beta2 contact and slightly affects the oxygen binding properties of the hemoglobin molecule. Hemoglobin Athens-Georgia has an increased affinity for oxygen, a normal heme-heme interaction and a normal Bohr effect. Hematological abnormalities are not associated with this variant."}
{"id": "PMID:8115", "title": "Sodium trichloroacetate-induced helical conformation of poly(L-lysine).", "content": "Sodium trichloroacetate which has been reported previously to be an effective denaturation reagent for proteins was applied to poly(L-lysine) and poly(L-glutamic acid) to see its effects on a coil-to-helix transition and on the chemical reactivities of the xi-amino group of poly(L-lysine). Addition of sodium trichloroacetate to poly(L-lysine) induced a helical conformation even at neutral pH where the xi-amino group of the polymer was protonated. On the other hand, little effect was observed on the coil-to-helix transition of poly(L-glutamic acid). The xi-amino group of poly(L-lysine) has an anomalously high reactivity with naphthoquinone 4,6-disulfonate carrying a negative charge. Sodium trichloroacetate inhibited the reaction of the xi-amino group with this reagent, while sodium trichloroacetate enhanced slightly the reaction of the xi-amino group of poly(L-lysine) with diazonium-1-H-tetrazole carrying a positive charge.", "contents": "Sodium trichloroacetate-induced helical conformation of poly(L-lysine). Sodium trichloroacetate which has been reported previously to be an effective denaturation reagent for proteins was applied to poly(L-lysine) and poly(L-glutamic acid) to see its effects on a coil-to-helix transition and on the chemical reactivities of the xi-amino group of poly(L-lysine). Addition of sodium trichloroacetate to poly(L-lysine) induced a helical conformation even at neutral pH where the xi-amino group of the polymer was protonated. On the other hand, little effect was observed on the coil-to-helix transition of poly(L-glutamic acid). The xi-amino group of poly(L-lysine) has an anomalously high reactivity with naphthoquinone 4,6-disulfonate carrying a negative charge. Sodium trichloroacetate inhibited the reaction of the xi-amino group with this reagent, while sodium trichloroacetate enhanced slightly the reaction of the xi-amino group of poly(L-lysine) with diazonium-1-H-tetrazole carrying a positive charge."}
{"id": "PMID:8116", "title": "Lysyl oxidase: a pituitary hormone-dependent enzyme.", "content": "Aldehyde-deficient non-crosslinked collagen obtained from lathyritic rats and collagen from penicillamine-treated rats, which is not deficient in aldehydes but the crosslinking of which is also inhibited, were implanted into the peritoneal cavity of hypophysectomized rats using the diffusion chamber technique. The enzyme lysyl oxidase which catalyses the aldehyde formation in certain lysyl residues of collagen and elastin was extracted from the skin of hypophysectomized rats. The activity of the enzyme was determined following its incubation with an L-[4,5-3H] lysine-labeled elastin substrate prepared from aortas of 17-day-old chick embryos. The result showed that the aldehyde deficient collagen did not crosslink while in the hypophysectomized animal indicating the lack of active lysyl oxidase in the rats. The enzyme activity in the skin of hypophysectomized animals was markedly reduced as compared with the controls indicating directly the dependance of lysyl oxidase activity on pituitary gland hormones.", "contents": "Lysyl oxidase: a pituitary hormone-dependent enzyme. Aldehyde-deficient non-crosslinked collagen obtained from lathyritic rats and collagen from penicillamine-treated rats, which is not deficient in aldehydes but the crosslinking of which is also inhibited, were implanted into the peritoneal cavity of hypophysectomized rats using the diffusion chamber technique. The enzyme lysyl oxidase which catalyses the aldehyde formation in certain lysyl residues of collagen and elastin was extracted from the skin of hypophysectomized rats. The activity of the enzyme was determined following its incubation with an L-[4,5-3H] lysine-labeled elastin substrate prepared from aortas of 17-day-old chick embryos. The result showed that the aldehyde deficient collagen did not crosslink while in the hypophysectomized animal indicating the lack of active lysyl oxidase in the rats. The enzyme activity in the skin of hypophysectomized animals was markedly reduced as compared with the controls indicating directly the dependance of lysyl oxidase activity on pituitary gland hormones."}
{"id": "PMID:8117", "title": "Isolation and characterization of a hemagglutinin from Amphitrite ornata, a polychaetous annelid.", "content": "Extracts of the marine polychaetous annelid, Amphitrite ornata, agglutinate rat, rabbit, chicken and human erythrocytes and in other work have been shown to inhibit the growth of Ehrlich ascites tumors in mice. Fractionation of extracts on Sephadex G-100 gave three active fractions with molecular weights of 30 000, 54 000 and 100 000. The 30 000 dalton fraction (B) was purified 72-fold by ammonium sulfate precipitation, gel filtration and preparative disc gel electrophoresis. The purified hemagglutinin, amphitritin, was homogenous on analytical disc gel electrophoresis at four different pH values and gave a sharp boundary in sedimentation velocity ultracentrifugation. The three fractions showed paralled specificity toward rat and chicken erythrocytes, the former giving the higher titer. The purified agglutinin was active toward human blood groups A, B and O and exhibited 4-fold higher activity toward group A. The hemagglutinin titer against rat red blood cells was lowered only by N-acetylgalactosamine, the terminal sugar residue of the group A determinant. None of the saccharides tested inhibited agglutination of chicken erythrocytes. Hemagglutinin activity was insensitive to dialysis or treatment with EDTA. The activity was not affected by digestion with trypsin or pronase, but was destroyed by phenol extraction. Analytical disc gel electrophoresis showed one protein band with high anodal mobility at pH 8.5, which was not affected by proteolytic enzymes but was removed by phenol. Activity was unaffected by heating at 70 degrees C for 30 min but was destroyed by similar treatemtn at 85 degrees C. Activity was at a maximum at pH 7-9 and decreased reversibly down to pH 4 at which point it was irreversibly inactivated. The higher molecular weight agglutinin (A1) could be dissociated to give amphitritin by treatment with 6M urea of precipitation in 55% (NH4)2SO4. This dissociation was not reversed by dialysis. Amphitritin is a glycoprotein with a molecular weight determined by gel filtration of 30 000 and by approach to equilibrium sedimentation of 32 000. Amino acid analysis showed a preponderance of aspartic and glutamic acids and relatively large amounts of glycine, proline, alanine, valine and cysteine. The carbohydrate moeity which represented 12.8% of the molecule, contained mannose, galactose, glucosamine and sialic acid. Amphitritin is the first hemagglutinin to be isolated from a polychaetous annelid.", "contents": "Isolation and characterization of a hemagglutinin from Amphitrite ornata, a polychaetous annelid. Extracts of the marine polychaetous annelid, Amphitrite ornata, agglutinate rat, rabbit, chicken and human erythrocytes and in other work have been shown to inhibit the growth of Ehrlich ascites tumors in mice. Fractionation of extracts on Sephadex G-100 gave three active fractions with molecular weights of 30 000, 54 000 and 100 000. The 30 000 dalton fraction (B) was purified 72-fold by ammonium sulfate precipitation, gel filtration and preparative disc gel electrophoresis. The purified hemagglutinin, amphitritin, was homogenous on analytical disc gel electrophoresis at four different pH values and gave a sharp boundary in sedimentation velocity ultracentrifugation. The three fractions showed paralled specificity toward rat and chicken erythrocytes, the former giving the higher titer. The purified agglutinin was active toward human blood groups A, B and O and exhibited 4-fold higher activity toward group A. The hemagglutinin titer against rat red blood cells was lowered only by N-acetylgalactosamine, the terminal sugar residue of the group A determinant. None of the saccharides tested inhibited agglutination of chicken erythrocytes. Hemagglutinin activity was insensitive to dialysis or treatment with EDTA. The activity was not affected by digestion with trypsin or pronase, but was destroyed by phenol extraction. Analytical disc gel electrophoresis showed one protein band with high anodal mobility at pH 8.5, which was not affected by proteolytic enzymes but was removed by phenol. Activity was unaffected by heating at 70 degrees C for 30 min but was destroyed by similar treatemtn at 85 degrees C. Activity was at a maximum at pH 7-9 and decreased reversibly down to pH 4 at which point it was irreversibly inactivated. The higher molecular weight agglutinin (A1) could be dissociated to give amphitritin by treatment with 6M urea of precipitation in 55% (NH4)2SO4. This dissociation was not reversed by dialysis. Amphitritin is a glycoprotein with a molecular weight determined by gel filtration of 30 000 and by approach to equilibrium sedimentation of 32 000. Amino acid analysis showed a preponderance of aspartic and glutamic acids and relatively large amounts of glycine, proline, alanine, valine and cysteine. The carbohydrate moeity which represented 12.8% of the molecule, contained mannose, galactose, glucosamine and sialic acid. Amphitritin is the first hemagglutinin to be isolated from a polychaetous annelid."}
{"id": "PMID:8118", "title": "Ceruloplasmin-anion interaction. A circular dichroism spectroscopic study.", "content": "The effect of anion binding to ceruloplasmin has been studied using absorption and cirbular dichroism spectral data. At anion to ceruloplasmin molar ratios approaching infinite, OCN-, N3- and SCN- bind to ceruloplasmin giving rise to similar alterations in circular dichroism and absorption spectra. The positive bands at 610 and 520 nm in circular dichroism spectra disappear, a negative one apperars at 600 nm and the peak at 450 nm is only slightly modified. There is a new negative band at 410 nm well-defined in OCN- ceruloplasmin spectra. The decrease in absorption at 610 nm is ascribed to the disruption of one type I Cu-S(cysteine) bond owing presumably to the changes induced by anions in the protein secondary structure. The new band at 410 nm is assigned to a charge transfer transition from the ligand replacing cysteine at its binding site. Both absorption and circular dichroism spectra show isobestic points indicating that anion binding to the enzyme, disruption of one of the two type I Cu-S bonds and coordination of this Cu to another protein residue take place simultaneously.", "contents": "Ceruloplasmin-anion interaction. A circular dichroism spectroscopic study. The effect of anion binding to ceruloplasmin has been studied using absorption and cirbular dichroism spectral data. At anion to ceruloplasmin molar ratios approaching infinite, OCN-, N3- and SCN- bind to ceruloplasmin giving rise to similar alterations in circular dichroism and absorption spectra. The positive bands at 610 and 520 nm in circular dichroism spectra disappear, a negative one apperars at 600 nm and the peak at 450 nm is only slightly modified. There is a new negative band at 410 nm well-defined in OCN- ceruloplasmin spectra. The decrease in absorption at 610 nm is ascribed to the disruption of one type I Cu-S(cysteine) bond owing presumably to the changes induced by anions in the protein secondary structure. The new band at 410 nm is assigned to a charge transfer transition from the ligand replacing cysteine at its binding site. Both absorption and circular dichroism spectra show isobestic points indicating that anion binding to the enzyme, disruption of one of the two type I Cu-S bonds and coordination of this Cu to another protein residue take place simultaneously."}
{"id": "PMID:8119", "title": "Fluorescence and the structure of proteins. XXI. Fluorescence of aminotyrosyl residues in peptides and helical proteins.", "content": "1. Five peptides containing tyrosine were converted to the 3-aminotyrosyl peptides by nitration with tetranitromethane and subseuqent reduction of the nitro groups to amino groups. The fluorescence of these aminotyrosyl residues was found to be quite similar to that of 3-aminotyrosine and it is concluded that the fluorescence is not sensitive to incorporation of the amino acid into the peptide chain. 2. Fluorescence of 3-aminotyrosine derivatives was sensitive, however, to the nature of the solvent; as the dielectric constant decreased, fluorescence was enhanced ten fold and the emission maximum shifted from the 350-370 nm value in aqueous solution to 320 nm. It is predicted that similar differences might be expected for exposed and buried aminotyrosyl residues in a protein. 3. Exposed tyrosyl residues on the helical protein tropomyosin and a helical segment of paramyosin were aminated in part (39% and 34% of the total tyrosyl residues, respectively). The fluorescence of the aminated tyrosyl residues on these proteins was similar to that of the aminotyrosyl peptides in an aqueous medium. Although the fluorescence efficiency of an aminotyrosyl residue was much lower than that of a tyrosyl residue, it was easy to distinguish the fluorescence of the aminotyrosyl residues (350-355 nm) on the protein from that arising from unmodified tyrosyl residues (305 nm).", "contents": "Fluorescence and the structure of proteins. XXI. Fluorescence of aminotyrosyl residues in peptides and helical proteins. 1. Five peptides containing tyrosine were converted to the 3-aminotyrosyl peptides by nitration with tetranitromethane and subseuqent reduction of the nitro groups to amino groups. The fluorescence of these aminotyrosyl residues was found to be quite similar to that of 3-aminotyrosine and it is concluded that the fluorescence is not sensitive to incorporation of the amino acid into the peptide chain. 2. Fluorescence of 3-aminotyrosine derivatives was sensitive, however, to the nature of the solvent; as the dielectric constant decreased, fluorescence was enhanced ten fold and the emission maximum shifted from the 350-370 nm value in aqueous solution to 320 nm. It is predicted that similar differences might be expected for exposed and buried aminotyrosyl residues in a protein. 3. Exposed tyrosyl residues on the helical protein tropomyosin and a helical segment of paramyosin were aminated in part (39% and 34% of the total tyrosyl residues, respectively). The fluorescence of the aminated tyrosyl residues on these proteins was similar to that of the aminotyrosyl peptides in an aqueous medium. Although the fluorescence efficiency of an aminotyrosyl residue was much lower than that of a tyrosyl residue, it was easy to distinguish the fluorescence of the aminotyrosyl residues (350-355 nm) on the protein from that arising from unmodified tyrosyl residues (305 nm)."}
{"id": "PMID:8120", "title": "Fluorine nuclear magnetic resonance studies of trifluoroacetylinsulin derivatives. Effects of salts and denaturants.", "content": "19F nuclear magnetic resonance spectroscopy has been used to study the effects of salts and denaturants on the structure and aggregation properties of several trifluoroacetyl derivatives of insulin. This technique has been shown to be a powerful tool in the study of specific sites on the protein molecule. Circular dichroic and sedimentation velocity studies were also carried out to aid in the interpretation of the magnetic resonance data. At pH 6.8 Zn2+ had no effect on the 19F magnetic resonance spectrum, however, citrate and acetate ions significantly sharpened the signal from the trifluoroacetyl probe at the N-terminal end (glycine A-1) of the insulin A chain. No alterations were observed in the S20,W value of circular dichroic spectra, suggesting that the probe had gained a considerable degree of motional freedom without changes in aggregation or conformational properties. In the absence of perturbants the trifluoroacetyl group on glycine A-1 showed considerably more motional freedom than on phenylalanine B-1. Guanidine hydrochloride and sodium dodecyl sulfate were used to study the unfolding of several trifluoroacetylinsulin derivatives. The results suggested differential alterations in the environments of the probes located at glycine A-1, phenylalanine B-1, and lysine B-29 in the insulin molecule as the concentration of perturbant was increased.", "contents": "Fluorine nuclear magnetic resonance studies of trifluoroacetylinsulin derivatives. Effects of salts and denaturants. 19F nuclear magnetic resonance spectroscopy has been used to study the effects of salts and denaturants on the structure and aggregation properties of several trifluoroacetyl derivatives of insulin. This technique has been shown to be a powerful tool in the study of specific sites on the protein molecule. Circular dichroic and sedimentation velocity studies were also carried out to aid in the interpretation of the magnetic resonance data. At pH 6.8 Zn2+ had no effect on the 19F magnetic resonance spectrum, however, citrate and acetate ions significantly sharpened the signal from the trifluoroacetyl probe at the N-terminal end (glycine A-1) of the insulin A chain. No alterations were observed in the S20,W value of circular dichroic spectra, suggesting that the probe had gained a considerable degree of motional freedom without changes in aggregation or conformational properties. In the absence of perturbants the trifluoroacetyl group on glycine A-1 showed considerably more motional freedom than on phenylalanine B-1. Guanidine hydrochloride and sodium dodecyl sulfate were used to study the unfolding of several trifluoroacetylinsulin derivatives. The results suggested differential alterations in the environments of the probes located at glycine A-1, phenylalanine B-1, and lysine B-29 in the insulin molecule as the concentration of perturbant was increased."}
{"id": "PMID:8121", "title": "Photosynthetic electron transport and electrochromic effects at sub-zero temperatures.", "content": "Spinach chloroplasts, suspended in a liquid medium containing ethyleneglycol, showed reversible absorbance changes near 700 and 518 nm due to P-700 and \"P-518\" in the region from -35 to -50 degrees C upon illumination. The kinetics were the same at both wavelengths, provided absorbance changes due to Photosystem II were suppressed. At both wavelengths, the decay was slowed down considerably, not only by the System I electron acceptor methyl viologen, but also by silicomolybdate. The effect of the latter compound is probably not due to the oxidation of the reduced acceptor of Photosystem I by silicomolybdate, but to the enhanced accessibility of the acceptor to some other oxidant. In the presence of both an electron donor and acceptor for System I, a strong stimulation of the extent of the light-induced absorbance increase at 518 nm was observed. The most effective donor tested was reduced N-methylphenazonium methosulphate (PMS). The light-induced difference spectrum was similar to spectra obtained earlier at room temperature, and indicated electrochromic band shifts of chlorophylls a and b and carotenoid, due to a large potential over the thylakoid membrane, caused by sustained electron transport. It was estimated that steady-state potentials of up to nearly 500 mV were obtained in this way; the potentials reversed only slowly in the dark, indicating a low conductance of the membrane. This decay was accelerated by gramicidin D. The absorbance changes were linearly proportional to the membrane potential.", "contents": "Photosynthetic electron transport and electrochromic effects at sub-zero temperatures. Spinach chloroplasts, suspended in a liquid medium containing ethyleneglycol, showed reversible absorbance changes near 700 and 518 nm due to P-700 and \"P-518\" in the region from -35 to -50 degrees C upon illumination. The kinetics were the same at both wavelengths, provided absorbance changes due to Photosystem II were suppressed. At both wavelengths, the decay was slowed down considerably, not only by the System I electron acceptor methyl viologen, but also by silicomolybdate. The effect of the latter compound is probably not due to the oxidation of the reduced acceptor of Photosystem I by silicomolybdate, but to the enhanced accessibility of the acceptor to some other oxidant. In the presence of both an electron donor and acceptor for System I, a strong stimulation of the extent of the light-induced absorbance increase at 518 nm was observed. The most effective donor tested was reduced N-methylphenazonium methosulphate (PMS). The light-induced difference spectrum was similar to spectra obtained earlier at room temperature, and indicated electrochromic band shifts of chlorophylls a and b and carotenoid, due to a large potential over the thylakoid membrane, caused by sustained electron transport. It was estimated that steady-state potentials of up to nearly 500 mV were obtained in this way; the potentials reversed only slowly in the dark, indicating a low conductance of the membrane. This decay was accelerated by gramicidin D. The absorbance changes were linearly proportional to the membrane potential."}
{"id": "PMID:8122", "title": "Redox potential of plastoquinone A in spinach chloroplasts.", "content": "The redox potential of plastoquinone A in spinach chloroplasts was determined. The midpoint potential of the quinone is about +80 mV at pH 7.0 with an n value of 2. The pH-dependence of the potential is -30 mV per pH between pH 4.0 and 5.7, and -60 mV per pH between pH 5.7 and 8.0. The change of the slope at pH 5.7 is interpreted as the protonation of the oxidized plastoquinone A.", "contents": "Redox potential of plastoquinone A in spinach chloroplasts. The redox potential of plastoquinone A in spinach chloroplasts was determined. The midpoint potential of the quinone is about +80 mV at pH 7.0 with an n value of 2. The pH-dependence of the potential is -30 mV per pH between pH 4.0 and 5.7, and -60 mV per pH between pH 5.7 and 8.0. The change of the slope at pH 5.7 is interpreted as the protonation of the oxidized plastoquinone A."}
{"id": "PMID:8123", "title": "Flash-induced absorption changes of the primary donor of photosystem II at 820 nm in chloroplasts inhibited by low pH or tris-treatment.", "content": "A comparative study is made, at 15 degrees C, of flash-induced absorption changes around 820 nm (attributed to the primary donors of Photosystems I and II) and 705 nm (Photosystem I only), in normal chloroplasts and in chloroplasts where O2 evolution was inhibited by low pH or by Tris-treatment. At pH 7.5, with untreated chloroplasts, the absorption changes around 820 nm are shown to be due to P-700 alone. Any contribution of the primary donor of Photosystem II should be in times shorter than 60 mus. When chloroplasts are inhibited at the donor side of Photosystem II by low pH, an additional absorption change at 820 nm appears with an amplitude which, at pH 4.0, is slightly higher than the signal due to oxidized P-700. This additional signal is attributed to the primary donor of Photosystem II. It decays (t 1/2 about 180 mus) mainly by back reaction with the primary acceptor and partly by reduction by another electron donor. Acid-washed chloroplasts resuspended at pH 7.5 still present the signal due to Photosystem II (t 1/2 about 120 mus). This shows that the acid inhibition of the first secondary donor of Photosystem II is irreversible. In Tris-treated chloroplasts, absorption changes at 820 nm due to the primary donor of Photosystem II are also observed, but to a lesser extent and only after some charge accumulation at the donor side. They decay with a half-time of 120 mus.", "contents": "Flash-induced absorption changes of the primary donor of photosystem II at 820 nm in chloroplasts inhibited by low pH or tris-treatment. A comparative study is made, at 15 degrees C, of flash-induced absorption changes around 820 nm (attributed to the primary donors of Photosystems I and II) and 705 nm (Photosystem I only), in normal chloroplasts and in chloroplasts where O2 evolution was inhibited by low pH or by Tris-treatment. At pH 7.5, with untreated chloroplasts, the absorption changes around 820 nm are shown to be due to P-700 alone. Any contribution of the primary donor of Photosystem II should be in times shorter than 60 mus. When chloroplasts are inhibited at the donor side of Photosystem II by low pH, an additional absorption change at 820 nm appears with an amplitude which, at pH 4.0, is slightly higher than the signal due to oxidized P-700. This additional signal is attributed to the primary donor of Photosystem II. It decays (t 1/2 about 180 mus) mainly by back reaction with the primary acceptor and partly by reduction by another electron donor. Acid-washed chloroplasts resuspended at pH 7.5 still present the signal due to Photosystem II (t 1/2 about 120 mus). This shows that the acid inhibition of the first secondary donor of Photosystem II is irreversible. In Tris-treated chloroplasts, absorption changes at 820 nm due to the primary donor of Photosystem II are also observed, but to a lesser extent and only after some charge accumulation at the donor side. They decay with a half-time of 120 mus."}
{"id": "PMID:8124", "title": "Membrane-bound ATPase in chloroplasts of Euglena gracilis.", "content": "Membrane-bound ATPase activities in chloroplasts of Euglena were examined. Ca2+- and Mg2+-dependent activities were relatively high in membrane preparations and could not be further activated by a number of procedures. The enzyme was found to be highly specific for purine nucleotides and was inhibited by the usual inhibitors of photophosphorylation. Km values of Ca2+ and Mg2+ ATPase for ATP were 2.5 and 2.1 mM, respectively. Both activities were competitively inhibited by ADP and inorganic phosphate. A relationship was found between Ca2+- or Mg2+-dependent ATPase activities and chloroplast completeness. The possibilities that these activities result from one enzyme depending on Ca2+ or Mg2+ or from two different enzymes are discussed.", "contents": "Membrane-bound ATPase in chloroplasts of Euglena gracilis. Membrane-bound ATPase activities in chloroplasts of Euglena were examined. Ca2+- and Mg2+-dependent activities were relatively high in membrane preparations and could not be further activated by a number of procedures. The enzyme was found to be highly specific for purine nucleotides and was inhibited by the usual inhibitors of photophosphorylation. Km values of Ca2+ and Mg2+ ATPase for ATP were 2.5 and 2.1 mM, respectively. Both activities were competitively inhibited by ADP and inorganic phosphate. A relationship was found between Ca2+- or Mg2+-dependent ATPase activities and chloroplast completeness. The possibilities that these activities result from one enzyme depending on Ca2+ or Mg2+ or from two different enzymes are discussed."}
{"id": "PMID:8125", "title": "Cytidine-5'-monophospho-N-acetylneuraminic acid galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide sialyltransferase in the neurohypophysis of the rabbit.", "content": "1. Cytidine-5'-monophospho-N-acetylneuraminic acid: (galactosyl-N-acetyl-galactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide sialyltransferase (CMP-NAcNeu: monosialoganglioside (GM1) sialyltransferase) activity was demonstrated in the neurohypophysis of the rabbit. 2. Optimum activity occurred at pH 6.5 and required the presence of exogenous galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide (GM1 ganglioside), detergent (Triton X-100), and divalent cation (Mn2+, Mg2+ or Ca2+). 3. The product of the reaction was characterized as N-acetylneuraminyl-galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide (GD1a) by ascending thin-layer chromatography. 4. Physiological stimulation of vasopressin secretion, by the substitution of 2.2% NaCl for drinking water for 14 days, had no effect on the enzyme activiity or the ganglioside content of the tissue.", "contents": "Cytidine-5'-monophospho-N-acetylneuraminic acid galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide sialyltransferase in the neurohypophysis of the rabbit. 1. Cytidine-5'-monophospho-N-acetylneuraminic acid: (galactosyl-N-acetyl-galactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide sialyltransferase (CMP-NAcNeu: monosialoganglioside (GM1) sialyltransferase) activity was demonstrated in the neurohypophysis of the rabbit. 2. Optimum activity occurred at pH 6.5 and required the presence of exogenous galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide (GM1 ganglioside), detergent (Triton X-100), and divalent cation (Mn2+, Mg2+ or Ca2+). 3. The product of the reaction was characterized as N-acetylneuraminyl-galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosyl-glucosylceramide (GD1a) by ascending thin-layer chromatography. 4. Physiological stimulation of vasopressin secretion, by the substitution of 2.2% NaCl for drinking water for 14 days, had no effect on the enzyme activiity or the ganglioside content of the tissue."}
{"id": "PMID:8126", "title": "The formation of cis-3-nonenal, trans-2-nonenal and hexanal from linoleic acid hydroperoxide isomers by a hydroperoxide cleavage enzyme system in cucumber (Cucumis sativus) fruits.", "content": "1. A particulate enzyme fraction and an acetone powder preparation from cucumber fruits cleaved 9- and 13-hydroperoxyoctadecadienoic acids to form volatile aldehydes and oxoacid fragments. 2. From the 9-hydroperoxide, the major volatile fragments were cis-3-nonenal and trans-2-nonenal using particulate enzyme and acetone powder preparations, respectively. 3. Hexanal was the only significant volatile fragment from the 13-hydroperoxide. 4. The particulate enzyme system was equally effective on both 9- and 13-hydroperoxide isomers and was fully active under anaerobic conditions and at pH 6.4. 5. An enzymic pathway for the biogenesis of hexanal, cis-3- and trans-2-nonenal (components of the characteristic flavour volatiles of cucumber) from linoleic acid is proposed. This involves the sequential activity of lipoxygenase, hydroperoxide cleavage and cis-3-: trans-2-enal isomerase enzymes.", "contents": "The formation of cis-3-nonenal, trans-2-nonenal and hexanal from linoleic acid hydroperoxide isomers by a hydroperoxide cleavage enzyme system in cucumber (Cucumis sativus) fruits. 1. A particulate enzyme fraction and an acetone powder preparation from cucumber fruits cleaved 9- and 13-hydroperoxyoctadecadienoic acids to form volatile aldehydes and oxoacid fragments. 2. From the 9-hydroperoxide, the major volatile fragments were cis-3-nonenal and trans-2-nonenal using particulate enzyme and acetone powder preparations, respectively. 3. Hexanal was the only significant volatile fragment from the 13-hydroperoxide. 4. The particulate enzyme system was equally effective on both 9- and 13-hydroperoxide isomers and was fully active under anaerobic conditions and at pH 6.4. 5. An enzymic pathway for the biogenesis of hexanal, cis-3- and trans-2-nonenal (components of the characteristic flavour volatiles of cucumber) from linoleic acid is proposed. This involves the sequential activity of lipoxygenase, hydroperoxide cleavage and cis-3-: trans-2-enal isomerase enzymes."}
{"id": "PMID:8127", "title": "Activity and properties of CTP: cholinephosphate cytidylyltransferase in adult and fetal rat lung.", "content": "Cholinephosphate cytidylyltransferase (CTP : cholinephosphate cytidylyltransferase, EC 2.7.7.15) is located in both the microsomal and supernatant fractions of adult lung when the tissue is homogenized in 0.145 M NaCl. The activity is located predominantly in the supernatant fraction in fetal lung. Cholinephosphate cytidylyltransferase in the supernatant from fetal lung is stimulated 4- to 6-fold by the additions of total lung lipid. Serine phosphoglycerides and inositol phosphoglycerides specifically caused stimulation whereas choline phosphoglycerides and ethanolamine phosphoglycerides produced no stimulation. Lysophosphatidylcholine cause some stimulation, but only at high concentrations. A number of detergents were investigated. All produced inhibition except for the ampholytic detergent, miranol H2M which was not inhibitory. None of the detergents produced any stimulation of activity. Cytidylyltransferase activity in fetal lung when assayed in the absence of lipid is about 25% of the adult. The activity when assayed in the presence of lipid is equal or slightly higher than adult levels. The activity, measured without added phospholipid, increases 5- to 6-fold within 12 h after birth, to values higher than in the adult. The activity, measured in the presence of phospholipid, increased almost linearly from -2 day until +1 day. There is an inverse relationship between the concentration of phospholipid in the fetal lung supernatant and the degree of lipid stimulation. Chromatographic experiments with Biogel A 1.5 columns have shown that cytidylyltransferase can exist in two molecular sizes, a small molecular size that requires phospholipid for activity, and a larger molecular weight species which does not require the addition of phospholipid for activity. Fetal lung has a higher proportion of the low molecular weight form than adult lung. The small molecular weight species can be converted to the larger molecular weight form by the addition of phospholipids.", "contents": "Activity and properties of CTP: cholinephosphate cytidylyltransferase in adult and fetal rat lung. Cholinephosphate cytidylyltransferase (CTP : cholinephosphate cytidylyltransferase, EC 2.7.7.15) is located in both the microsomal and supernatant fractions of adult lung when the tissue is homogenized in 0.145 M NaCl. The activity is located predominantly in the supernatant fraction in fetal lung. Cholinephosphate cytidylyltransferase in the supernatant from fetal lung is stimulated 4- to 6-fold by the additions of total lung lipid. Serine phosphoglycerides and inositol phosphoglycerides specifically caused stimulation whereas choline phosphoglycerides and ethanolamine phosphoglycerides produced no stimulation. Lysophosphatidylcholine cause some stimulation, but only at high concentrations. A number of detergents were investigated. All produced inhibition except for the ampholytic detergent, miranol H2M which was not inhibitory. None of the detergents produced any stimulation of activity. Cytidylyltransferase activity in fetal lung when assayed in the absence of lipid is about 25% of the adult. The activity when assayed in the presence of lipid is equal or slightly higher than adult levels. The activity, measured without added phospholipid, increases 5- to 6-fold within 12 h after birth, to values higher than in the adult. The activity, measured in the presence of phospholipid, increased almost linearly from -2 day until +1 day. There is an inverse relationship between the concentration of phospholipid in the fetal lung supernatant and the degree of lipid stimulation. Chromatographic experiments with Biogel A 1.5 columns have shown that cytidylyltransferase can exist in two molecular sizes, a small molecular size that requires phospholipid for activity, and a larger molecular weight species which does not require the addition of phospholipid for activity. Fetal lung has a higher proportion of the low molecular weight form than adult lung. The small molecular weight species can be converted to the larger molecular weight form by the addition of phospholipids."}
{"id": "PMID:8128", "title": "Effect of portacaval anastomosis on the activities of hepatic enzymes related to cholesterol and bile acid metabolism in rats.", "content": "1. The effect of a portacaval anastomosis on the activities of hepatic enzymes related to cholesterol metabolism was investigated in rats. 2. Portacaval anastomosis led to a fall in body weight and liver weight/body weight ratio, and to a rise in the activities of hydroxymethylglutaryl-CoA reductase and cholesterol 7alpha-hydroxylase per g of liver. The net effect was to maintain a normal activity of both enzymes per 100 g of rat. Diurnal rhythm in the activities of both enzymes was maintained after portacaval anastomosis. 3. The rate of excretion of total bile acids, per 100 g of rat, in bile fistula rats was not significantly decreased by portacaval anastomosis.", "contents": "Effect of portacaval anastomosis on the activities of hepatic enzymes related to cholesterol and bile acid metabolism in rats. 1. The effect of a portacaval anastomosis on the activities of hepatic enzymes related to cholesterol metabolism was investigated in rats. 2. Portacaval anastomosis led to a fall in body weight and liver weight/body weight ratio, and to a rise in the activities of hydroxymethylglutaryl-CoA reductase and cholesterol 7alpha-hydroxylase per g of liver. The net effect was to maintain a normal activity of both enzymes per 100 g of rat. Diurnal rhythm in the activities of both enzymes was maintained after portacaval anastomosis. 3. The rate of excretion of total bile acids, per 100 g of rat, in bile fistula rats was not significantly decreased by portacaval anastomosis."}
{"id": "PMID:8129", "title": "Coupling in secondary transport. Effect of electrical potentials on the kinetics of ion linked co-transport.", "content": "In a previous paper kinetic equations of secondary active transport by cotransport have been derived. In the present paper these equations have been expanded by including the effect of an electrical potential difference in order to make them applicable to the more realistic systems of secondary active transport driven by the gradients of Na+ or H+. Thermodynamically an electrical potential difference is as a driving force fully exchangeable with an equivalent chemical potential difference. This is not necessarily so for the kinetics of co-transport. It is not always the same whether a given difference in electrochemical activity of the driver ion is mainly osmotic, i.e. due to difference in concentration, or electric, i.e. due to a difference in the electrochemical activity coefficient. In most cases a difference in concentration is more effective in driving co-transport than is an equivalent difference in electrical potential leading to the same difference in electrical activity. The effectiveness of the latter highly depends on the model, whether it is of the affinity type or of the velocity type, but also on whether the loaded or the unloaded carrier bears an electrical charge. With the same electrical potential difference co-transport is as a rule faster if the ternary complex rather than the empty carrier is charged. Also the \"standard parameters\", (see Glossary, page 62) Jmax and Km, of the overall transport respond differently to the introduction of an electrical potential difference, depending on the model. So an electrical potential difference will mostly affect Km if the loaded carrier is ionic, and mostly Jmax if the empty carrier is ionic, provided that the mobility of the loaded carrier is greater than that of the empty one. On the other hand, distinctive criteria between affinity type and velocity type models are partly affected by an electrical potential difference. If the translocation steps of loaded and unloaded carrier are no longer rate limiting for the overall transport, electrical effects on the transport rate are bound to vanish as does the activation by co-transport.", "contents": "Coupling in secondary transport. Effect of electrical potentials on the kinetics of ion linked co-transport. In a previous paper kinetic equations of secondary active transport by cotransport have been derived. In the present paper these equations have been expanded by including the effect of an electrical potential difference in order to make them applicable to the more realistic systems of secondary active transport driven by the gradients of Na+ or H+. Thermodynamically an electrical potential difference is as a driving force fully exchangeable with an equivalent chemical potential difference. This is not necessarily so for the kinetics of co-transport. It is not always the same whether a given difference in electrochemical activity of the driver ion is mainly osmotic, i.e. due to difference in concentration, or electric, i.e. due to a difference in the electrochemical activity coefficient. In most cases a difference in concentration is more effective in driving co-transport than is an equivalent difference in electrical potential leading to the same difference in electrical activity. The effectiveness of the latter highly depends on the model, whether it is of the affinity type or of the velocity type, but also on whether the loaded or the unloaded carrier bears an electrical charge. With the same electrical potential difference co-transport is as a rule faster if the ternary complex rather than the empty carrier is charged. Also the \"standard parameters\", (see Glossary, page 62) Jmax and Km, of the overall transport respond differently to the introduction of an electrical potential difference, depending on the model. So an electrical potential difference will mostly affect Km if the loaded carrier is ionic, and mostly Jmax if the empty carrier is ionic, provided that the mobility of the loaded carrier is greater than that of the empty one. On the other hand, distinctive criteria between affinity type and velocity type models are partly affected by an electrical potential difference. If the translocation steps of loaded and unloaded carrier are no longer rate limiting for the overall transport, electrical effects on the transport rate are bound to vanish as does the activation by co-transport."}
{"id": "PMID:8130", "title": "Tryptic- and chymotryptic-like proteinases in early and late preimplantation mouse blastocysts.", "content": "Neutral tryptic- and chymotryptic-like enzyme activities have been identified in extracts of early and late mouse blastocyts. The enzyme activities are distinguishable my means of: (a) reactivity with specific naphthylamide derivatives; (b) reactivity with tosyl-L-lysine-chloromethyl ketone or L-tosylamido-2-phenylethyl-chloromethyl ketone, respectively; (c) electrophoretic mobilities; and (d) specific activity profiles of late vs. early blastocysts.", "contents": "Tryptic- and chymotryptic-like proteinases in early and late preimplantation mouse blastocysts. Neutral tryptic- and chymotryptic-like enzyme activities have been identified in extracts of early and late mouse blastocyts. The enzyme activities are distinguishable my means of: (a) reactivity with specific naphthylamide derivatives; (b) reactivity with tosyl-L-lysine-chloromethyl ketone or L-tosylamido-2-phenylethyl-chloromethyl ketone, respectively; (c) electrophoretic mobilities; and (d) specific activity profiles of late vs. early blastocysts."}
{"id": "PMID:8131", "title": "PHrmonal specificity of the melanotropin-sensitive adenylate cyclase of mouse melanoma and effect of cyclic AMP on the tyrosinase activity of mouse melanoma cells, in vitro.", "content": "Transplantable mouse melanomas possess a melanotropin-sensitive adenylate cyclase system which is responsive to alpha-melanotropin, beta-melanotropin, adrenocorticotropin (ACTH) and prostaglandin E1. It was found that sensitivity to ACTH was not directed towards the ACTH activity but to the intrinsic melanotropin activity of the ACTH molecule. Therefore, the melanotropin-sensitive adenylate cyclase system is hormonally specific to the intrinsic melanotropin activity of peptide hormones and is unique in the melanoma tissue. The significance of the sensitivity to prostaglandin E1 is obscure at present. The melanotropin-sensitive adenylate cyclase requires the presence of Mg2+ or Mn2+, for its enzymic activity. Ca2+ inhibit the enzyme in the presence of a wide range of concentrations of Mg2+. The enzymic activity is ATP concentration-dependent and the saturation concentration appears to be 1 mM. The enzyme is very labile in the unfractionated tumor homogenates. A washed 11000 X g particulate fraction, representing about 30-60% of the total enzymic activity, was found to be more stable and could be stored at 5 degrees C for 2 h without appreciable loss of the activity. This fraction retained sensitivity to melanotropin, prostaglandin E1 and NaF. About 20% of the activity of the tumor homogenate could not be sedimented by centrifugation at 105000 X g for 60 min. This \"soluble\" fraction was not responsive to melanotropin, prostaglandin E1 and NaF and might be a degradative product produced by the fractionation. Cyclic AMP and alpha-melanotropin were able to increase the tyrosinase activity of isolated mouse melanoma-cells in vitro under the same conditions.", "contents": "PHrmonal specificity of the melanotropin-sensitive adenylate cyclase of mouse melanoma and effect of cyclic AMP on the tyrosinase activity of mouse melanoma cells, in vitro. Transplantable mouse melanomas possess a melanotropin-sensitive adenylate cyclase system which is responsive to alpha-melanotropin, beta-melanotropin, adrenocorticotropin (ACTH) and prostaglandin E1. It was found that sensitivity to ACTH was not directed towards the ACTH activity but to the intrinsic melanotropin activity of the ACTH molecule. Therefore, the melanotropin-sensitive adenylate cyclase system is hormonally specific to the intrinsic melanotropin activity of peptide hormones and is unique in the melanoma tissue. The significance of the sensitivity to prostaglandin E1 is obscure at present. The melanotropin-sensitive adenylate cyclase requires the presence of Mg2+ or Mn2+, for its enzymic activity. Ca2+ inhibit the enzyme in the presence of a wide range of concentrations of Mg2+. The enzymic activity is ATP concentration-dependent and the saturation concentration appears to be 1 mM. The enzyme is very labile in the unfractionated tumor homogenates. A washed 11000 X g particulate fraction, representing about 30-60% of the total enzymic activity, was found to be more stable and could be stored at 5 degrees C for 2 h without appreciable loss of the activity. This fraction retained sensitivity to melanotropin, prostaglandin E1 and NaF. About 20% of the activity of the tumor homogenate could not be sedimented by centrifugation at 105000 X g for 60 min. This \"soluble\" fraction was not responsive to melanotropin, prostaglandin E1 and NaF and might be a degradative product produced by the fractionation. Cyclic AMP and alpha-melanotropin were able to increase the tyrosinase activity of isolated mouse melanoma-cells in vitro under the same conditions."}
{"id": "PMID:8132", "title": "The effect of beta-adrenergic blocking agents on experimental porphyria induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in vivo and in vitro.", "content": "The effect of DL-propranolol on 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced experimental porphyria was studied. DL-Propranolol, a beta-adrenergic blocking agent with non-specific membrane effects, partially inhibited 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced delta-aminolevulinate synthetase activity both in rats and in chick embryo liver cells in culture. In rats, DL-propranolol decreased urinary delta-aminolevulinate and porphobilinogen but no change occurred in the 24-h urinary excretion of total porphyrins and in the concentration of porphyrins in the liver. In cultured chick embryo liver cells treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine, DL-propranolol decreased accumulation of porphyrins in the medium. D-Propranolol, oxprenolol and quinidine acted like DL-propranolol in chick embryo liver cells in culture treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine. Pindolol, practolol and lidocaine had no effect. Phenobarbitone had a synergistic effect on the induction of delta-aminolevulinate synthetase by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine in cultures of chick embryo liver cells. This induction was partially inhibited by propranolol. However, the increased accumulation of porphyrins in the medium caused by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine was inhibited by the addition of phenobarbitone. This inhibited induction was further decreased by propranolol. Most of our results indicate that the drugs tested act mainly by their effects on membranes.", "contents": "The effect of beta-adrenergic blocking agents on experimental porphyria induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in vivo and in vitro. The effect of DL-propranolol on 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced experimental porphyria was studied. DL-Propranolol, a beta-adrenergic blocking agent with non-specific membrane effects, partially inhibited 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced delta-aminolevulinate synthetase activity both in rats and in chick embryo liver cells in culture. In rats, DL-propranolol decreased urinary delta-aminolevulinate and porphobilinogen but no change occurred in the 24-h urinary excretion of total porphyrins and in the concentration of porphyrins in the liver. In cultured chick embryo liver cells treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine, DL-propranolol decreased accumulation of porphyrins in the medium. D-Propranolol, oxprenolol and quinidine acted like DL-propranolol in chick embryo liver cells in culture treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine. Pindolol, practolol and lidocaine had no effect. Phenobarbitone had a synergistic effect on the induction of delta-aminolevulinate synthetase by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine in cultures of chick embryo liver cells. This induction was partially inhibited by propranolol. However, the increased accumulation of porphyrins in the medium caused by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine was inhibited by the addition of phenobarbitone. This inhibited induction was further decreased by propranolol. Most of our results indicate that the drugs tested act mainly by their effects on membranes."}
{"id": "PMID:8133", "title": "Studies on the production and assessment of experimental histidinemia in the rat.", "content": "Intraperitoneal administration to rats of D- or DL-alpha-hydrazinoimidazolylpropionic acid was found to produce a substantial inactivation of hepatic histidine ammonia-lyase (EC 4.3.1.3) in vivo. Proportional to this loss in enzyme activity was an impairment of the ability of treated rats to oxidize L-[ring-2-14C] histidine to 14CO2. Rats in which hepatic histidine ammonia-lyase activity was either depressed by DL-hydrazinoimidazolylproprionic acid injection or elevated by feeding a high protein diet displayed proportionately altered rates of 3H2O release into plasma water following L-[3-3H] histidine administration. Plasma L-histidine clearance following loading with this amino acid was similarly affected by these treatments. Administration of DL-alphal-hydrazinoimisazolylproprionic acid to rats was also found to inactivate non-specifically pyridoxal 5-phosphate enzymes in vivo; pyridoxine injection was found to reverse the DL-alpha-hydrazinoimidazolylproprionic acid-induced inactivation of hepatic aspartate aminotransferase (EC 2.6.1.1) in vivo, but not that of hepatic histidine ammonia-lyase. These findings demonstrate that histidine ammonia-lyase is the rate-limiting factor in L-histidine degradation in the rat. The potential usefulness of DL-hydrazinoimidazolylproprionic acid in the production of an animal model for histidinemia (hereditary histidine ammonia-lyase deficiency) is discussed.", "contents": "Studies on the production and assessment of experimental histidinemia in the rat. Intraperitoneal administration to rats of D- or DL-alpha-hydrazinoimidazolylpropionic acid was found to produce a substantial inactivation of hepatic histidine ammonia-lyase (EC 4.3.1.3) in vivo. Proportional to this loss in enzyme activity was an impairment of the ability of treated rats to oxidize L-[ring-2-14C] histidine to 14CO2. Rats in which hepatic histidine ammonia-lyase activity was either depressed by DL-hydrazinoimidazolylproprionic acid injection or elevated by feeding a high protein diet displayed proportionately altered rates of 3H2O release into plasma water following L-[3-3H] histidine administration. Plasma L-histidine clearance following loading with this amino acid was similarly affected by these treatments. Administration of DL-alphal-hydrazinoimisazolylproprionic acid to rats was also found to inactivate non-specifically pyridoxal 5-phosphate enzymes in vivo; pyridoxine injection was found to reverse the DL-alpha-hydrazinoimidazolylproprionic acid-induced inactivation of hepatic aspartate aminotransferase (EC 2.6.1.1) in vivo, but not that of hepatic histidine ammonia-lyase. These findings demonstrate that histidine ammonia-lyase is the rate-limiting factor in L-histidine degradation in the rat. The potential usefulness of DL-hydrazinoimidazolylproprionic acid in the production of an animal model for histidinemia (hereditary histidine ammonia-lyase deficiency) is discussed."}
{"id": "PMID:8134", "title": "Photooxidation of methionine with immobilized methylene blue as photooxidizer.", "content": "Methylene blue immobilized on porous glass beads was used to catalyze the photooxidation of methionine alone and the methionine residues of lysozyme. A solution of 2 mM methionine in 50% acetic acid was oxidized to methionine sulfoxide in the presence of immobilized methylene blue after 6 h of photooxidation at 37 degrees C. Selective photooxidation of the methionyl residues in lysozyme was achieved after 26 h of reaction in 84% acetic acid at 4 degrees C. The specific activity of lysozyme exposed to light in the presence of methylene blue decreased by 94%, while that of a lysozyme solution in the presence of methylene blue not exposed to light decreased by 21%. The lysozyme solution exposed to light but not containing the methylene blue beads lost 33% of its specific activity after the same period of photooxidation. It was shown that the decrease in enzyme activity was not caused by adsorption of the enzyme onto the beads.", "contents": "Photooxidation of methionine with immobilized methylene blue as photooxidizer. Methylene blue immobilized on porous glass beads was used to catalyze the photooxidation of methionine alone and the methionine residues of lysozyme. A solution of 2 mM methionine in 50% acetic acid was oxidized to methionine sulfoxide in the presence of immobilized methylene blue after 6 h of photooxidation at 37 degrees C. Selective photooxidation of the methionyl residues in lysozyme was achieved after 26 h of reaction in 84% acetic acid at 4 degrees C. The specific activity of lysozyme exposed to light in the presence of methylene blue decreased by 94%, while that of a lysozyme solution in the presence of methylene blue not exposed to light decreased by 21%. The lysozyme solution exposed to light but not containing the methylene blue beads lost 33% of its specific activity after the same period of photooxidation. It was shown that the decrease in enzyme activity was not caused by adsorption of the enzyme onto the beads."}
{"id": "PMID:8135", "title": "A lysyl residue at the NADP binding site of ferredoxin-NADP reductase.", "content": "Dansyl chloride, at low molar ratio, inactivates ferredoxin-NADP reductase (NADPH:ferredoxin oxidoreductase, EC 1.6.7.1). The complete protection afforded either by NADP or NADPH suggests a direct involvement of the active site. Experiments with [Me-14C] dansyl chloride showed that about 1.5 residues per flavin were dansylated: by differential labelling experiments using NADP, it has been proved that enzyme inactivation is due to dansylation of one residue. The group modified has been identified as the epsilon-amino group of a lysine. The pH-inactivation profile indicates that this essential group has an apparent pKa of 8.7. The dansylated flavoprotein seems to maintain its native conformation; it shows a fluorescent chromophore with a peak at 335 nm. The modified enzyme has lost the capacity to form a complex with NADP, nevertheless it interacts normally with ferredoxin. It is concluded that the loss of catalytic activity which parallels the dansylation of a lysyl residue occurs because this residue is essential for the binding of the pyridine nucleotide substrate. Protection experiments with a series of coenzyme analogs further indicate that this lysyl residue interacts, most likely, with the 2'-phosphate moiety of NADP(H).", "contents": "A lysyl residue at the NADP binding site of ferredoxin-NADP reductase. Dansyl chloride, at low molar ratio, inactivates ferredoxin-NADP reductase (NADPH:ferredoxin oxidoreductase, EC 1.6.7.1). The complete protection afforded either by NADP or NADPH suggests a direct involvement of the active site. Experiments with [Me-14C] dansyl chloride showed that about 1.5 residues per flavin were dansylated: by differential labelling experiments using NADP, it has been proved that enzyme inactivation is due to dansylation of one residue. The group modified has been identified as the epsilon-amino group of a lysine. The pH-inactivation profile indicates that this essential group has an apparent pKa of 8.7. The dansylated flavoprotein seems to maintain its native conformation; it shows a fluorescent chromophore with a peak at 335 nm. The modified enzyme has lost the capacity to form a complex with NADP, nevertheless it interacts normally with ferredoxin. It is concluded that the loss of catalytic activity which parallels the dansylation of a lysyl residue occurs because this residue is essential for the binding of the pyridine nucleotide substrate. Protection experiments with a series of coenzyme analogs further indicate that this lysyl residue interacts, most likely, with the 2'-phosphate moiety of NADP(H)."}
{"id": "PMID:8136", "title": "Specfic irreversible inhibition of sweet-almond beta-glucosidase by some beta-glycopyranosylepoxyalkanes and beta-d-glucopyranosyl isothiocyanate.", "content": "beta-D-Glucopyranosyl-(1S and 1R)-epoxyethanes (I and II), 1-(beta-D-glucopyranosyl)-(2R and 2S)-2,3-epoxypropanes (III and IV), beta-D-glucopyranosyl isothiocyanate (V) and beta-D-galactopyranosylepoxyethane (VI) are active-site-directed irreversible inhibitors of sweet-almond beta-glucosidase B (beta-D-Glucoside glucohydrolase, EC 3.2.1.21). Formation of the covalent bond is preceded by the binding of these inhibitors in the active site of the enzyme. This is testitified by the competitive character of inhibition of beta-glucosidase component B by compounds I-VI at the early period and by the protection of the enzyme from inactivation by its competitive inhibitors D-glucose and 1,5-D-gluconolactone. Epoxides I-IV are bound covalently with componet B at a molar ratio 1 : 1 as shown with the aid of 14C-labelled inhibitors. The release of the label from modified enzyme (E-I covalent) by treatment with hydroxylamine suggests the formation of an ester bond between inhibitors I-IV and the carboxyl group of the enzyme active site. The pH dependence curve of the inactivation rate of beta-glucosidase B is of a bell-shaped form for V and of a sigmoid character for I-IV and points to the involvement of the active site groups with pKa 5.6-5.9 and 4.2-4.4.", "contents": "Specfic irreversible inhibition of sweet-almond beta-glucosidase by some beta-glycopyranosylepoxyalkanes and beta-d-glucopyranosyl isothiocyanate. beta-D-Glucopyranosyl-(1S and 1R)-epoxyethanes (I and II), 1-(beta-D-glucopyranosyl)-(2R and 2S)-2,3-epoxypropanes (III and IV), beta-D-glucopyranosyl isothiocyanate (V) and beta-D-galactopyranosylepoxyethane (VI) are active-site-directed irreversible inhibitors of sweet-almond beta-glucosidase B (beta-D-Glucoside glucohydrolase, EC 3.2.1.21). Formation of the covalent bond is preceded by the binding of these inhibitors in the active site of the enzyme. This is testitified by the competitive character of inhibition of beta-glucosidase component B by compounds I-VI at the early period and by the protection of the enzyme from inactivation by its competitive inhibitors D-glucose and 1,5-D-gluconolactone. Epoxides I-IV are bound covalently with componet B at a molar ratio 1 : 1 as shown with the aid of 14C-labelled inhibitors. The release of the label from modified enzyme (E-I covalent) by treatment with hydroxylamine suggests the formation of an ester bond between inhibitors I-IV and the carboxyl group of the enzyme active site. The pH dependence curve of the inactivation rate of beta-glucosidase B is of a bell-shaped form for V and of a sigmoid character for I-IV and points to the involvement of the active site groups with pKa 5.6-5.9 and 4.2-4.4."}
{"id": "PMID:8137", "title": "Denaturation of subtilisin BPN' and its derivatives in aqueous guanidine hydrochloride solutions.", "content": "The denaturation of subtilisin BPN' (EC 3.4.21.14) in guanidine hydrochloride was studied in order to find possible reasons for the exceptional stability of this enzyme against the action of denaturing agents including guanidine hydrochloride. Chemically modified subtilisins, i.e., phenylmethanesulfonylsubtilisin and thio-subtilisin, were  completely denatured in 2 M guanidine hydrochloride at pH 7 without autolysis but they were stable in 0.5 M guanidine hydrochloride for at least 60 h. On the other hand, once completely denatured, the subtilisins remained inactive and in highly unfolded conformations for 60 h or longer after transfer into 0.5 M guanidine solution at pH 7 or 9. No enzymatic activity was regained when the guanidine concentration was lowered to almost zero. We concluded from these and other results described in this paper that this enzyme was thermodynamically unstable in 2 M guanidine hydrochloride at 20 degrees C and at pH 7. We wish to point out the possibility that the denaturation of this enzyme could indeed be irreversible.", "contents": "Denaturation of subtilisin BPN' and its derivatives in aqueous guanidine hydrochloride solutions. The denaturation of subtilisin BPN' (EC 3.4.21.14) in guanidine hydrochloride was studied in order to find possible reasons for the exceptional stability of this enzyme against the action of denaturing agents including guanidine hydrochloride. Chemically modified subtilisins, i.e., phenylmethanesulfonylsubtilisin and thio-subtilisin, were  completely denatured in 2 M guanidine hydrochloride at pH 7 without autolysis but they were stable in 0.5 M guanidine hydrochloride for at least 60 h. On the other hand, once completely denatured, the subtilisins remained inactive and in highly unfolded conformations for 60 h or longer after transfer into 0.5 M guanidine solution at pH 7 or 9. No enzymatic activity was regained when the guanidine concentration was lowered to almost zero. We concluded from these and other results described in this paper that this enzyme was thermodynamically unstable in 2 M guanidine hydrochloride at 20 degrees C and at pH 7. We wish to point out the possibility that the denaturation of this enzyme could indeed be irreversible."}
{"id": "PMID:8138", "title": "Purification and characterization of the two molecular forms of Aspergillus oryzae acid protease.", "content": "The isolation and partial characterization of the acid proteases A1 and A2 (EC3.4.23.6) from Aspergillus oryzae grown on solid bran culture are described. The purified preparations were essentially homogeneous by several criteria including sedimentation analysis and polyacrylamide gel electrophoresis. The physiochemical properties of the proteases A1 and A2 were as follows (in the order: A1, A2): molecular weight: 63 000 & 32 000; sedimentation coefficient s20, w: 3.93 and 3.16 S; diffusion constant D20, w, 5.63 - 10(-7) and 8.61 - 10(-7) CM2/S, partial specific volume, v: 0.73 ml/g for both; nitrogen content: 16.30 and 13.42%; E1% 1 cm at 280 nm: 5.9 and 11.1. The two enzymes had the same pH optima in the acid pH range, and both activated bovine pancreatic trypsinogen. The enzymes were essentially of the same amino acid composition and immunologically cross-reacted with each other. The protease A2 contained little or no carbohydrate, whereas the protease A1 was glycoprotein, containing 49% carbohydrate comprising glucose, mannose, and galactose. These results suggest that the protein portion of acid protease A1 is the same as that of acid protease A2.", "contents": "Purification and characterization of the two molecular forms of Aspergillus oryzae acid protease. The isolation and partial characterization of the acid proteases A1 and A2 (EC3.4.23.6) from Aspergillus oryzae grown on solid bran culture are described. The purified preparations were essentially homogeneous by several criteria including sedimentation analysis and polyacrylamide gel electrophoresis. The physiochemical properties of the proteases A1 and A2 were as follows (in the order: A1, A2): molecular weight: 63 000 & 32 000; sedimentation coefficient s20, w: 3.93 and 3.16 S; diffusion constant D20, w, 5.63 - 10(-7) and 8.61 - 10(-7) CM2/S, partial specific volume, v: 0.73 ml/g for both; nitrogen content: 16.30 and 13.42%; E1% 1 cm at 280 nm: 5.9 and 11.1. The two enzymes had the same pH optima in the acid pH range, and both activated bovine pancreatic trypsinogen. The enzymes were essentially of the same amino acid composition and immunologically cross-reacted with each other. The protease A2 contained little or no carbohydrate, whereas the protease A1 was glycoprotein, containing 49% carbohydrate comprising glucose, mannose, and galactose. These results suggest that the protein portion of acid protease A1 is the same as that of acid protease A2."}
{"id": "PMID:8139", "title": "Steady-state studies of the actin-activated adenosine triphosphatase activity of myosin.", "content": "Reconstituted actomyosin (ATP phosphohydrolase, EC 3.6.1.3) (0.400 mg F-actin/mg myosin) in 10.0 muM ATP loses 96% of its specific ATPase activity when its reaction concentration is decreased from 42.0 mug/ml down to 0.700 mug/ml. The loss of specific activity at the very low enzyme concentrations is prevented by the addition of more F-actin to 17.6 mug/ml. It is concluded that at low actomyosin concentrations the complex dissociates into free myosin with a very low specific ATPase activity and free F-actin with no ATPase. The dissociation of the essential low molecular weight subunits of myosin from the heavy chains at very low actomyosin concentrations may be a contributing factor. Actomyosin has its maximum specific activity at pH 7.8-8.2. The Km for ATP is 9.4 muM, which is at least 20-fold greater than myosin's Km for ATP. The actin-activated ATPase of myosin follows hyperbolic kinetics with varying F-actin concentrations. The Km values for F-actin are 0.110 muM (4.95 mug/ml) at pH 7.4 and 0.241 muM (10.8 mug/ml) at pH 7.8. The actin-activated maximum turnover numbers for myosin are 9.3 s-1 at pH 7.4 and 11.6 s-1 at pH 7.8. The actomyosin ATPase is inhibited by KCl. This KCl inhibition is not competitive with respect to F-actin, and it is not a simple form of non-competitive inhibition.", "contents": "Steady-state studies of the actin-activated adenosine triphosphatase activity of myosin. Reconstituted actomyosin (ATP phosphohydrolase, EC 3.6.1.3) (0.400 mg F-actin/mg myosin) in 10.0 muM ATP loses 96% of its specific ATPase activity when its reaction concentration is decreased from 42.0 mug/ml down to 0.700 mug/ml. The loss of specific activity at the very low enzyme concentrations is prevented by the addition of more F-actin to 17.6 mug/ml. It is concluded that at low actomyosin concentrations the complex dissociates into free myosin with a very low specific ATPase activity and free F-actin with no ATPase. The dissociation of the essential low molecular weight subunits of myosin from the heavy chains at very low actomyosin concentrations may be a contributing factor. Actomyosin has its maximum specific activity at pH 7.8-8.2. The Km for ATP is 9.4 muM, which is at least 20-fold greater than myosin's Km for ATP. The actin-activated ATPase of myosin follows hyperbolic kinetics with varying F-actin concentrations. The Km values for F-actin are 0.110 muM (4.95 mug/ml) at pH 7.4 and 0.241 muM (10.8 mug/ml) at pH 7.8. The actin-activated maximum turnover numbers for myosin are 9.3 s-1 at pH 7.4 and 11.6 s-1 at pH 7.8. The actomyosin ATPase is inhibited by KCl. This KCl inhibition is not competitive with respect to F-actin, and it is not a simple form of non-competitive inhibition."}
{"id": "PMID:8140", "title": "Human fat cell adenylate cyclase. Enzyme characterization and guanine nucleotide effects on epinephrine responsiveness in cell membranes.", "content": "Human adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) has been studied in preparations of fat cell membranes (\"ghosts\"). As reported earlier, under ordinary assay conditions (1.0 mM ATP, 5 mM Mg2+, 30 degrees C, 10 min incubation) the enzyme was activated 6-fold by epinephrine in the presence of the GTP analog, 5'-guanylyl-imidodiphosphate [GMP-P(NH)P] (Cooper, B. et al. (1975) J. Clin. Invest. 56, 1350-1353). Basal activity was highest during the first 2 min of incubation then slowed and was linear for at least the next 18 min. Epinephrine, added alone, was often without effect. but sometimes maintained the initial high rate of basal activity. GMP-P(NH)P alone produced inhibition (\"lag\") of basal enzyme early in the incubation periods. Augmentation of epinephrine effect by GMP-P(NH)P, which also proceeded after a brief (2 min) lag period, was noted over a wide range of substrate (ATP) concentrations. GTP inhibited basal levels of the enzyme by about 50%. GTP also allowed expression of an epinephrine effect, but only in the sense that the hormone abolished the inhibition by GTP. Occasionally a slight stimulatory effect on epinephrine action was seen with GTP. At high Mg2+ concentration (greater than 10 mM) or elevated temperatures (greater than 30 degrees C) GMP-P(NH)P alone activated the enzyme. Maximal activity of human fat cell adenylate cyclase was seen at 50 mM Mg2+, 1.0 mM ATP, pH 8.2, and 37 degrees C in the presence of 10(-4) M GMP-P(NH)P; under these conditions addition of epinephrine did not further enhance activity. Human fat cell adenylate cyclase of adults was insensitive to ACTH and glucagon even in the presence of GMP-P(NH)P.", "contents": "Human fat cell adenylate cyclase. Enzyme characterization and guanine nucleotide effects on epinephrine responsiveness in cell membranes. Human adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) has been studied in preparations of fat cell membranes (\"ghosts\"). As reported earlier, under ordinary assay conditions (1.0 mM ATP, 5 mM Mg2+, 30 degrees C, 10 min incubation) the enzyme was activated 6-fold by epinephrine in the presence of the GTP analog, 5'-guanylyl-imidodiphosphate [GMP-P(NH)P] (Cooper, B. et al. (1975) J. Clin. Invest. 56, 1350-1353). Basal activity was highest during the first 2 min of incubation then slowed and was linear for at least the next 18 min. Epinephrine, added alone, was often without effect. but sometimes maintained the initial high rate of basal activity. GMP-P(NH)P alone produced inhibition (\"lag\") of basal enzyme early in the incubation periods. Augmentation of epinephrine effect by GMP-P(NH)P, which also proceeded after a brief (2 min) lag period, was noted over a wide range of substrate (ATP) concentrations. GTP inhibited basal levels of the enzyme by about 50%. GTP also allowed expression of an epinephrine effect, but only in the sense that the hormone abolished the inhibition by GTP. Occasionally a slight stimulatory effect on epinephrine action was seen with GTP. At high Mg2+ concentration (greater than 10 mM) or elevated temperatures (greater than 30 degrees C) GMP-P(NH)P alone activated the enzyme. Maximal activity of human fat cell adenylate cyclase was seen at 50 mM Mg2+, 1.0 mM ATP, pH 8.2, and 37 degrees C in the presence of 10(-4) M GMP-P(NH)P; under these conditions addition of epinephrine did not further enhance activity. Human fat cell adenylate cyclase of adults was insensitive to ACTH and glucagon even in the presence of GMP-P(NH)P."}
{"id": "PMID:8141", "title": "NADP+-specific isocitrate dehydrogenase of Excherichia coli. III. Two-step purification employing affinity chromatography.", "content": "The NADP+-specific isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42) of Excherichia coli has been purified to electrophoretic homogeneity by a two-step purification procedure employing affinity chromatography. The overall yield of enzyme was 30% with specific activity 125 mumol/min per ng protein. Electrophoretic homogeneity of the isocitrate dehydrogenase was deterimed in analytical polyacrylamide gels in a Tris/acetate/EDTA buffer system at pH 7.5 and in a citrate/phosphate buffer system at pH 6.0.", "contents": "NADP+-specific isocitrate dehydrogenase of Excherichia coli. III. Two-step purification employing affinity chromatography. The NADP+-specific isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42) of Excherichia coli has been purified to electrophoretic homogeneity by a two-step purification procedure employing affinity chromatography. The overall yield of enzyme was 30% with specific activity 125 mumol/min per ng protein. Electrophoretic homogeneity of the isocitrate dehydrogenase was deterimed in analytical polyacrylamide gels in a Tris/acetate/EDTA buffer system at pH 7.5 and in a citrate/phosphate buffer system at pH 6.0."}
{"id": "PMID:8142", "title": "L-Rhamnose dehydrogenase of pullularia pullulans.", "content": "Growth of Pullularia pullulans on L-rhamnose induces formation of L-rhamnofuranose dehydrogenase, whichreversibly converts L-rhamnofuranose to L-rhamnono-gamma-lactone with the concomitant reduction of NAD, but not of NADP. The dehydrogenase was purified 100-fold by MnCl(2) treatment...", "contents": "L-Rhamnose dehydrogenase of pullularia pullulans. Growth of Pullularia pullulans on L-rhamnose induces formation of L-rhamnofuranose dehydrogenase, whichreversibly converts L-rhamnofuranose to L-rhamnono-gamma-lactone with the concomitant reduction of NAD, but not of NADP. The dehydrogenase was purified 100-fold by MnCl(2) treatment..."}
{"id": "PMID:8143", "title": "Human erythrocyte glutathione reductase. I. Purification and properties.", "content": "1. Glutathione reductase (NAD(P)H:oxidized-glutathione oxidoreductase, EC. 1.6.4.2) from human erythrocytes was purified 49 000-fold with an overall yield of 15% and a 280/460 nm absorbance ratio of 6.03. The procedure used was the method of Worthington and Rosemeyer modified by addition of heating and recrystallization. 2. It was concluded from the results of purification, electrofocusing and inhibition studies that glutathione reductase is a single enzyme which used both NADPH and NADH as hydrogen donors. 3. Apoenzyme cross-reacts with the antibody to the holoenzyme but has a slightly reduced affinity to the antibody. Apoenzyme can be removed from the hemolysate by heating and centrifugation without loss of holoenzyme. 4. Indirect immunological assay of the specific activity of the erythrocyte glutathione reductase is possible in the enzyme saturated with FAD.", "contents": "Human erythrocyte glutathione reductase. I. Purification and properties. 1. Glutathione reductase (NAD(P)H:oxidized-glutathione oxidoreductase, EC. 1.6.4.2) from human erythrocytes was purified 49 000-fold with an overall yield of 15% and a 280/460 nm absorbance ratio of 6.03. The procedure used was the method of Worthington and Rosemeyer modified by addition of heating and recrystallization. 2. It was concluded from the results of purification, electrofocusing and inhibition studies that glutathione reductase is a single enzyme which used both NADPH and NADH as hydrogen donors. 3. Apoenzyme cross-reacts with the antibody to the holoenzyme but has a slightly reduced affinity to the antibody. Apoenzyme can be removed from the hemolysate by heating and centrifugation without loss of holoenzyme. 4. Indirect immunological assay of the specific activity of the erythrocyte glutathione reductase is possible in the enzyme saturated with FAD."}
{"id": "PMID:8144", "title": "Spectrophotometric pH titrations and nitration with tetranitromethane of the tyrosyl residues in yeast phosphoglycerate kinase.", "content": "Spectrophotometric pH titrations of phosphoglycerate kinase (EC 2.7.2.3) reveal seven tyrosyl residues. In the native state one tyrosyl residue has pKapp equal to 9.3, another has pKapp of about 12.9, and five have pKapp values close to 11.0. Titration above pH 10 causes concomitant reduction of the catalytic activity. Reactivation of the enzyme occurs during storage at pH 7.8. In 6 M guanidine - HCl seven tyrosyl residues with pKapp values equal to 10.0 appear. Nitration of three tyrosyl residues occurs easily when tetranitromethane is used in excess. Four tyrosyl residues appear to be masked or buried. The tyrosyl residue having pKapp equal to 9.3 can be selectively nitrated. Simultaneously the enzyme loses 40% of its catalytic activity. No change in the Km value for one or the other of the two substrates, MgATP or 3-phospho-D-glycerate, was observed in the mononitrated enzyme. On the other hand MgATP protects the tyrosyl residue from nitration whereas 3-phospho-D-glycerate at corresponding condition appears harmless. These results suggest the low ionizing tyrosyl residue to be situated close to the binding site of MgATP, possibly in a pocket just behind. Circular dichroism measurements indicated that minor successive changes occur in the secondary structure, mainly the beta-structure, when the enzyme is being nitrated. It is reasonable to think that these structural changes, possible in combination with steric hindrance, are responsible for the decrease in catalytic activity. Dimerization of the enzyme occurs if the single thiol group is not masked before the tetranitromethane treatment.", "contents": "Spectrophotometric pH titrations and nitration with tetranitromethane of the tyrosyl residues in yeast phosphoglycerate kinase. Spectrophotometric pH titrations of phosphoglycerate kinase (EC 2.7.2.3) reveal seven tyrosyl residues. In the native state one tyrosyl residue has pKapp equal to 9.3, another has pKapp of about 12.9, and five have pKapp values close to 11.0. Titration above pH 10 causes concomitant reduction of the catalytic activity. Reactivation of the enzyme occurs during storage at pH 7.8. In 6 M guanidine - HCl seven tyrosyl residues with pKapp values equal to 10.0 appear. Nitration of three tyrosyl residues occurs easily when tetranitromethane is used in excess. Four tyrosyl residues appear to be masked or buried. The tyrosyl residue having pKapp equal to 9.3 can be selectively nitrated. Simultaneously the enzyme loses 40% of its catalytic activity. No change in the Km value for one or the other of the two substrates, MgATP or 3-phospho-D-glycerate, was observed in the mononitrated enzyme. On the other hand MgATP protects the tyrosyl residue from nitration whereas 3-phospho-D-glycerate at corresponding condition appears harmless. These results suggest the low ionizing tyrosyl residue to be situated close to the binding site of MgATP, possibly in a pocket just behind. Circular dichroism measurements indicated that minor successive changes occur in the secondary structure, mainly the beta-structure, when the enzyme is being nitrated. It is reasonable to think that these structural changes, possible in combination with steric hindrance, are responsible for the decrease in catalytic activity. Dimerization of the enzyme occurs if the single thiol group is not masked before the tetranitromethane treatment."}
{"id": "PMID:8145", "title": "Purification and properties of extracellular alpha-glucosidase of a thermophile, Bacillus thermoglucosidus KP 1006.", "content": "An extracecular alpha-glucosidase (alpha-D-glucoside glycohydrolase, EC 3.2.1.20) of a thermophile, Bacillus thermoglucosidius KP 1006, was purified about 350-fold. The purified enzyme had a specific activity of 164 mumol of p-nitrophenyl-alpha-D-glucopyranoside hydrolyzed per min at  60 degrees C and pH 6.8 per mg of protein. The molecular weight was estimated at 55 000. The pH and temperature optima for activity were 5.0--6.0 and 75 degrees C, respectively. Below 40 degrees C, the activity was less than 4.5% of the optimym. The enzyme showed a high specificity for alpha-D-glucopyranoside. The maximal hydrolyzing velocity per substrate diminished in the order: phenyl-alpha-D-glucopyranoside, p-nitrophenyl-alpha-D-glucopyranoside, isomaltose, methyl-alpha-glycopyranoside. The respective Km values were 3.0, 0.23, 3.2 and 27 mM. The activity was trace for turanose, and not detectable for sucrose, trehalose, raffinose, melezitose, maltose, maltotriose, phenyl-alpha-D-maltoside, dextran, dextrin and starch. Tris, p-nitrophenyl-alpha-D-xylopyranoside, glucose and glucono-delta-lactone blocked competitively the enzyme with respect to p-nitrophenyl-alpha-D-glucopyranoside. The Ki values were 0.12, 0.14, 2.2 and 2.4 mM, respectively. The activity was affected by heavy metal ions, but insensitive to EDTA, p-chloromercuribenzoate and iodoacetate. The enzyme was stable up to 60 degrees C, and inactivated rapidly at temperatures beyond 72 degrees C. The pH range for stability was 4.0--11.0 at 31 degrees C, and 6.0--8.5 at 55.5 degrees C. At 25 degrees C, the enzyme failed to be inactivated in 45% ethanol, in 7.2 M urea, and in 0.06% sodium dodecyl sulfate, but the tolerance was extremely reduced at 60 degrees C.", "contents": "Purification and properties of extracellular alpha-glucosidase of a thermophile, Bacillus thermoglucosidus KP 1006. An extracecular alpha-glucosidase (alpha-D-glucoside glycohydrolase, EC 3.2.1.20) of a thermophile, Bacillus thermoglucosidius KP 1006, was purified about 350-fold. The purified enzyme had a specific activity of 164 mumol of p-nitrophenyl-alpha-D-glucopyranoside hydrolyzed per min at  60 degrees C and pH 6.8 per mg of protein. The molecular weight was estimated at 55 000. The pH and temperature optima for activity were 5.0--6.0 and 75 degrees C, respectively. Below 40 degrees C, the activity was less than 4.5% of the optimym. The enzyme showed a high specificity for alpha-D-glucopyranoside. The maximal hydrolyzing velocity per substrate diminished in the order: phenyl-alpha-D-glucopyranoside, p-nitrophenyl-alpha-D-glucopyranoside, isomaltose, methyl-alpha-glycopyranoside. The respective Km values were 3.0, 0.23, 3.2 and 27 mM. The activity was trace for turanose, and not detectable for sucrose, trehalose, raffinose, melezitose, maltose, maltotriose, phenyl-alpha-D-maltoside, dextran, dextrin and starch. Tris, p-nitrophenyl-alpha-D-xylopyranoside, glucose and glucono-delta-lactone blocked competitively the enzyme with respect to p-nitrophenyl-alpha-D-glucopyranoside. The Ki values were 0.12, 0.14, 2.2 and 2.4 mM, respectively. The activity was affected by heavy metal ions, but insensitive to EDTA, p-chloromercuribenzoate and iodoacetate. The enzyme was stable up to 60 degrees C, and inactivated rapidly at temperatures beyond 72 degrees C. The pH range for stability was 4.0--11.0 at 31 degrees C, and 6.0--8.5 at 55.5 degrees C. At 25 degrees C, the enzyme failed to be inactivated in 45% ethanol, in 7.2 M urea, and in 0.06% sodium dodecyl sulfate, but the tolerance was extremely reduced at 60 degrees C."}
{"id": "PMID:8146", "title": "Neutral alpha-mannosidase activity in human serum.", "content": "Two types of alpha-mannosidase (alpha-D-mannoside mannohydrolase, EC 3.2.1.24) with neutral pH optima exist in serum. The activity with an optimum between pH 6.0 and 6.4 is similar to alpha-mannosidase C, described earlier in tissues. The second activity, with a pH optimum between pH 5.2 and 5.8 is the dominant form in serum. These two forms can be differentiated from each other by gel-filtration, chromatography on DEAE-cellulose or chromatography on Concanavalin-A Sepharose. Using the chromatographic techniques, the serum type neutral activity co-elutes with the acidic forms of the enzyme. However, these two forms can be easily distinguished by effect of pH, heating or inhibition by the substrate methyl-alpha-D-mannopyranoside. The presence of the serum type alpha-mannosidase activity is discussed with respect to mannosidosis, a lysosomal storage disease.", "contents": "Neutral alpha-mannosidase activity in human serum. Two types of alpha-mannosidase (alpha-D-mannoside mannohydrolase, EC 3.2.1.24) with neutral pH optima exist in serum. The activity with an optimum between pH 6.0 and 6.4 is similar to alpha-mannosidase C, described earlier in tissues. The second activity, with a pH optimum between pH 5.2 and 5.8 is the dominant form in serum. These two forms can be differentiated from each other by gel-filtration, chromatography on DEAE-cellulose or chromatography on Concanavalin-A Sepharose. Using the chromatographic techniques, the serum type neutral activity co-elutes with the acidic forms of the enzyme. However, these two forms can be easily distinguished by effect of pH, heating or inhibition by the substrate methyl-alpha-D-mannopyranoside. The presence of the serum type alpha-mannosidase activity is discussed with respect to mannosidosis, a lysosomal storage disease."}
{"id": "PMID:8147", "title": "Purification and properties of a new aminopeptidase from Escherichia COLI K12.", "content": "An aminopeptidase (EC 3.4.11.-) capmable of hydrolyzing L-alanyl-beta-naphthyl-amide and certain other aminoacyl beta-naphthylamides was purified to homogeneity from extracts of Exherichia coli K-12. The enzyme, designated aminopeptidase II, is a monomeric protein of mol. wt. 100 000. It exhibits a broad pH optimum in the range pH 7.0--9.0. Although Zn2+, Fe3+ and Cr3+ are strong inhibitors of enzyme activity, a metal requirement for catalysis could not be firmly established. Neither sulfhydryl reagents nor serine protease inhibitors affected enzyme activity.", "contents": "Purification and properties of a new aminopeptidase from Escherichia COLI K12. An aminopeptidase (EC 3.4.11.-) capmable of hydrolyzing L-alanyl-beta-naphthyl-amide and certain other aminoacyl beta-naphthylamides was purified to homogeneity from extracts of Exherichia coli K-12. The enzyme, designated aminopeptidase II, is a monomeric protein of mol. wt. 100 000. It exhibits a broad pH optimum in the range pH 7.0--9.0. Although Zn2+, Fe3+ and Cr3+ are strong inhibitors of enzyme activity, a metal requirement for catalysis could not be firmly established. Neither sulfhydryl reagents nor serine protease inhibitors affected enzyme activity."}
{"id": "PMID:8148", "title": "Proton transfer to a charged dye bound to the alpha-chymotrypsin active site studied by laser photolysis.", "content": "Pulsed laser photolysis has been used to study the very rapid relaxation of the complex of alpha-chymotrypsin (EC 3.4.21.1) with the coloured inhibitor Biebrich Scarlet. The light absorption causes the dissociation of the proton in the dye naphthol ring and we are able to follow the recombination process under conditions of different ionic strength and pH. The recombination is markedly influenced by the pH around pH 7. The data suggest the existence of relevant interactions in the active site area between the hydrophobic binding site and the proton relay system of the enzyme.", "contents": "Proton transfer to a charged dye bound to the alpha-chymotrypsin active site studied by laser photolysis. Pulsed laser photolysis has been used to study the very rapid relaxation of the complex of alpha-chymotrypsin (EC 3.4.21.1) with the coloured inhibitor Biebrich Scarlet. The light absorption causes the dissociation of the proton in the dye naphthol ring and we are able to follow the recombination process under conditions of different ionic strength and pH. The recombination is markedly influenced by the pH around pH 7. The data suggest the existence of relevant interactions in the active site area between the hydrophobic binding site and the proton relay system of the enzyme."}
{"id": "PMID:8149", "title": "Chemical investigations on pig kidney aminoacylase.", "content": "1. Preparations of purified pig kidney aminoacylase (N-Acylamino-acid amidohydrolase, EC 3.5.1.14) were obtained by Sephadex and DEAE-cellulose chromatography in homogeneous form as judged by polyacrylamide gel electrophoresis and immunoelectrophoresis. 2. The apparent molecular weight of the enzyme, determined by gel filtration, was about 86 000. After treatment with mercaptoethanol, performic acid or sodium dodecyl sulphate a band with an apparent molecular weight of approximately 43 000 was observed in polyacrylamide gels containing sodium dodecyl sulphate. Thus pig kidney aminoacylase seems to be composed of two subunits. 3. The amino acid composition of the enzyme was determined. Aminoacylase contains 772 amino acids, which corresponds to a molecular weight of 85 500. 12 tryptophan and 12 half-cystine residues were found. 4. Each subunit of the enzyme contains two -SH groups of different reactivity and two disulfide bonds one of which is easily cleaved by -SH compounds, the second only by performic acid oxidation. 5. Chemical modification of two -SH groups abolishes the catalytic activity of aminoacylase. Cleavage of two disulfide bonds also inactivates the enzyme. It is suggested that the enzyme has two active sites each containing an essential -SH group and disulfide bond. One active site is assumed to be part of each subunit.", "contents": "Chemical investigations on pig kidney aminoacylase. 1. Preparations of purified pig kidney aminoacylase (N-Acylamino-acid amidohydrolase, EC 3.5.1.14) were obtained by Sephadex and DEAE-cellulose chromatography in homogeneous form as judged by polyacrylamide gel electrophoresis and immunoelectrophoresis. 2. The apparent molecular weight of the enzyme, determined by gel filtration, was about 86 000. After treatment with mercaptoethanol, performic acid or sodium dodecyl sulphate a band with an apparent molecular weight of approximately 43 000 was observed in polyacrylamide gels containing sodium dodecyl sulphate. Thus pig kidney aminoacylase seems to be composed of two subunits. 3. The amino acid composition of the enzyme was determined. Aminoacylase contains 772 amino acids, which corresponds to a molecular weight of 85 500. 12 tryptophan and 12 half-cystine residues were found. 4. Each subunit of the enzyme contains two -SH groups of different reactivity and two disulfide bonds one of which is easily cleaved by -SH compounds, the second only by performic acid oxidation. 5. Chemical modification of two -SH groups abolishes the catalytic activity of aminoacylase. Cleavage of two disulfide bonds also inactivates the enzyme. It is suggested that the enzyme has two active sites each containing an essential -SH group and disulfide bond. One active site is assumed to be part of each subunit."}
{"id": "PMID:8150", "title": "HCO-3-activated adenosine triphosphatase in intestinal mucosa of the eel.", "content": "An HCO-3-activated and SCN--inhibited ATPase (ATP phosphohydrolase, EC 3.6.1.3) found in homogenates of intestinal mucosa of the eel was solubilized by Triton X-100. Optimal HCO-3-concentration and pH for the enzyme were 25 mM and 8.7, respectively. HCO-3-ATPase activity in both homogenate and solubilized preparations increased after seawater adaptation. This adaptive increase in enzyme activity was also observed in the gills and the kidney. The HCO-3-ATPase seems to be related to transport mechanisms, especially for Cl-, in osmoregulatory surfaces of the eel.", "contents": "HCO-3-activated adenosine triphosphatase in intestinal mucosa of the eel. An HCO-3-activated and SCN--inhibited ATPase (ATP phosphohydrolase, EC 3.6.1.3) found in homogenates of intestinal mucosa of the eel was solubilized by Triton X-100. Optimal HCO-3-concentration and pH for the enzyme were 25 mM and 8.7, respectively. HCO-3-ATPase activity in both homogenate and solubilized preparations increased after seawater adaptation. This adaptive increase in enzyme activity was also observed in the gills and the kidney. The HCO-3-ATPase seems to be related to transport mechanisms, especially for Cl-, in osmoregulatory surfaces of the eel."}
{"id": "PMID:8151", "title": "Properties of guanylate cyclase in adult rat liver and several Morris hepatomas.", "content": "Guanylate cyclase (GTP pyrophyosphate-lyase (cyclizing), EC 4.6.1.2) activity was examined in preparations from normal rat liver and a series of Morris hepatomas. Homogenate gyanylate cyclase activites were 3.2, 1.6 and 1.2 nmol cyclic GMP formed per min/g tissue ihe non-substrate analogs of IMP were weak inhibitors of this enzyme, GMP and four of its analogs had Ki values ranging from 30 to 80 muM. The GMP analogs (8-azaGMP, 7-deaza-8-azaGMP, 2'-dGMP and beta-D-arabinosylGMP) and GMP were competitive inhibitors with respect to GTP.", "contents": "Properties of guanylate cyclase in adult rat liver and several Morris hepatomas. Guanylate cyclase (GTP pyrophyosphate-lyase (cyclizing), EC 4.6.1.2) activity was examined in preparations from normal rat liver and a series of Morris hepatomas. Homogenate gyanylate cyclase activites were 3.2, 1.6 and 1.2 nmol cyclic GMP formed per min/g tissue ihe non-substrate analogs of IMP were weak inhibitors of this enzyme, GMP and four of its analogs had Ki values ranging from 30 to 80 muM. The GMP analogs (8-azaGMP, 7-deaza-8-azaGMP, 2'-dGMP and beta-D-arabinosylGMP) and GMP were competitive inhibitors with respect to GTP."}
{"id": "PMID:8152", "title": "Role of lysyl-tRNA in the regulation of lysine biosynthesis in Escherichia coli K12.", "content": "A mutant of lysyl-tRNA synthetase has been isolated in Escherichia coli K12. With this strain the Kmapp for lysine is 25 fold higher than with the parental strain. The percentage of charged tRNAlys in vivo is only 7 per cent (as against 65 per cent with HFR H). Under these conditions no derepression of synthesis is observed for three lysine biosynthetic enzymes (AK III, ASA-dehydrogenase, DAP-decarboxylase) ; a partial derepression is obtained in the case of the dhdp-reductase. Thus lysyl-tRNA does not act as the only corepressor molecule in the lysine regulon.", "contents": "Role of lysyl-tRNA in the regulation of lysine biosynthesis in Escherichia coli K12. A mutant of lysyl-tRNA synthetase has been isolated in Escherichia coli K12. With this strain the Kmapp for lysine is 25 fold higher than with the parental strain. The percentage of charged tRNAlys in vivo is only 7 per cent (as against 65 per cent with HFR H). Under these conditions no derepression of synthesis is observed for three lysine biosynthetic enzymes (AK III, ASA-dehydrogenase, DAP-decarboxylase) ; a partial derepression is obtained in the case of the dhdp-reductase. Thus lysyl-tRNA does not act as the only corepressor molecule in the lysine regulon."}
{"id": "PMID:8153", "title": "Mechanistic studies of glutamine synthetase from Escherichia coli. An integrated mechanism for biosynthesis, transferase, ATPase reaction.", "content": "The mechanism of biosynthetic, transferase, ATPase, and transphosphorylation reactions catalyzed by unadenylylated glutamine synthetase from E. coli was studied. Activation complex(es) involved in the biosynthetic reaction are produced in the presence of either Mg2+ or Mn2+ ; however, with the Mn2+-enzyme inhibition by the product, ADP, is so great that the overall forward biosynthetic reaction cannot be detected with the known assay methods. Binding studies show that substrates (except for NH3 and NH2OH which are not reported here) can bind to the enzyme in a random manner and that binding of the ATP-glutamate, ADP-Pi or ADP-arsenate pairs is strongly synergistic. Inhibition and binding studies show that the same binding site is utilized for glutamate and glutamine in biosynthetic and transferase reactions, respectively, and that a common nucleotide binding site is used for all reactions studied. Studies of the reverse biosynthetic reaction and results of fluorescent titration experiments suggest that both arsenate and orthophosphate bind at a site which overlaps the gamma-phosphate site of nucleoside triphosphate. In the reverse biosynthetic and transferase reactions, ATP serves as a substrate for the Mn2+-enzyme but not for the Mg2+-enzyme. The ATP supported transferase activity of Mn2+-enzyme is probably facilitated by the generation of ADP through ATP hydrolysis. When AMP was the only nucleotide substrate added, it was converted to ATP with concomitant formation of two equivalents of glutamate, under the reverse biosynthetic reaction conditions, and no ADP was detected. The reversibility of 180 transfer between orthophosphate and gamma-acyl group of glutamate was confirmed. ATPase activity of Mg2+ and Mn2+ unadenylylated enzymes is about the same. Both enzymes forms catalyze transphosphorylation reactions between various purine nucleoside triphosphates and nucleoside diphosphates under biosynthetic reaction conditions. The data are consistent with the hypothesis that a single active center is utilized for all reactions studied. Two stepwise mecanisms that could explain the results are discussed.", "contents": "Mechanistic studies of glutamine synthetase from Escherichia coli. An integrated mechanism for biosynthesis, transferase, ATPase reaction. The mechanism of biosynthetic, transferase, ATPase, and transphosphorylation reactions catalyzed by unadenylylated glutamine synthetase from E. coli was studied. Activation complex(es) involved in the biosynthetic reaction are produced in the presence of either Mg2+ or Mn2+ ; however, with the Mn2+-enzyme inhibition by the product, ADP, is so great that the overall forward biosynthetic reaction cannot be detected with the known assay methods. Binding studies show that substrates (except for NH3 and NH2OH which are not reported here) can bind to the enzyme in a random manner and that binding of the ATP-glutamate, ADP-Pi or ADP-arsenate pairs is strongly synergistic. Inhibition and binding studies show that the same binding site is utilized for glutamate and glutamine in biosynthetic and transferase reactions, respectively, and that a common nucleotide binding site is used for all reactions studied. Studies of the reverse biosynthetic reaction and results of fluorescent titration experiments suggest that both arsenate and orthophosphate bind at a site which overlaps the gamma-phosphate site of nucleoside triphosphate. In the reverse biosynthetic and transferase reactions, ATP serves as a substrate for the Mn2+-enzyme but not for the Mg2+-enzyme. The ATP supported transferase activity of Mn2+-enzyme is probably facilitated by the generation of ADP through ATP hydrolysis. When AMP was the only nucleotide substrate added, it was converted to ATP with concomitant formation of two equivalents of glutamate, under the reverse biosynthetic reaction conditions, and no ADP was detected. The reversibility of 180 transfer between orthophosphate and gamma-acyl group of glutamate was confirmed. ATPase activity of Mg2+ and Mn2+ unadenylylated enzymes is about the same. Both enzymes forms catalyze transphosphorylation reactions between various purine nucleoside triphosphates and nucleoside diphosphates under biosynthetic reaction conditions. The data are consistent with the hypothesis that a single active center is utilized for all reactions studied. Two stepwise mecanisms that could explain the results are discussed."}
{"id": "PMID:8154", "title": "Effects of activators on chemically modified yeast hexokinase.", "content": "Enzymic studies performed with chemically modified yeast hexokinase (ATP : D-hexose-6-phosphotransferase) confirm previous results indicating that the sulfhydryl, imidazol and most of the reactive amino groups do not seem to be directly implicated in the enzyme active site. On the other hand the modification of these functional groups of the enzyme does not affect the transition between the acidic inactive form to an active enzyme form after deprotonation. The chemically modified forms of hexokinase and the native enzyme are affected in the same way by activators (citrate, D-malate, 3-phosphoglycerate and Pi) when the activity was measured at pH 6.6. Moreover the loss of enzyme activity observed in the course of the chemical modifications is accompanied by an increase of the activation effect. This increase must be related to some reorganization of the enzyme active site in presence of the effectors, since the same effect was observed when hexokinase was denatured with 3M urea at pH 7.5. However no increase in the activation effect was observed when the denaturation was carried out at pH 6.5 At this pH the loss in activity and the change of optical absorption at 286 nm were much slower than at pH 7.5, which indicates a great difference in the protein structure between these pHs.", "contents": "Effects of activators on chemically modified yeast hexokinase. Enzymic studies performed with chemically modified yeast hexokinase (ATP : D-hexose-6-phosphotransferase) confirm previous results indicating that the sulfhydryl, imidazol and most of the reactive amino groups do not seem to be directly implicated in the enzyme active site. On the other hand the modification of these functional groups of the enzyme does not affect the transition between the acidic inactive form to an active enzyme form after deprotonation. The chemically modified forms of hexokinase and the native enzyme are affected in the same way by activators (citrate, D-malate, 3-phosphoglycerate and Pi) when the activity was measured at pH 6.6. Moreover the loss of enzyme activity observed in the course of the chemical modifications is accompanied by an increase of the activation effect. This increase must be related to some reorganization of the enzyme active site in presence of the effectors, since the same effect was observed when hexokinase was denatured with 3M urea at pH 7.5. However no increase in the activation effect was observed when the denaturation was carried out at pH 6.5 At this pH the loss in activity and the change of optical absorption at 286 nm were much slower than at pH 7.5, which indicates a great difference in the protein structure between these pHs."}
{"id": "PMID:8155", "title": "Phospholipases A1 and A2 of rat liver plasma membranes; mechanism of action.", "content": "While V/S plots of phospholipase A1 show a phase transition, kinetic behaviour of phospholipase A2 acting in the same concentration range is hyperbolic. However after phospholipase A2 has been solubilized from the plasma membranes by 1 M NaCl, the V/S curve shows a phase transition. Membrane-bound phospholipase A1 shows a narrow optimum pH at 8.5 -9, while phospholipase A2 activity presents only small variations between pH 7 and 9.5. Towards exogenous phospholipids at the optimum pH 8.5 of phospholipase A1, the specific activity of the latter is 3-fold higher than phospholipase A2 specific activity. On the contrary towards endogenous phospholipids, phospolipase A2 activity is higher than phospholipase A2 activity. Moreover labeled endogenous PE hydrolysis by phospholipase A2 is decreased by addition of non labeled exogenous PE into the incubation medium. All these data suggest that the active site of phospholipase A1 is turned to the outside and acts only on exogenous substrates: for phospholipase A2 it would be inside, and exogenous phospholipids could be hydrolyzed only after penetrating the membrane.", "contents": "Phospholipases A1 and A2 of rat liver plasma membranes; mechanism of action. While V/S plots of phospholipase A1 show a phase transition, kinetic behaviour of phospholipase A2 acting in the same concentration range is hyperbolic. However after phospholipase A2 has been solubilized from the plasma membranes by 1 M NaCl, the V/S curve shows a phase transition. Membrane-bound phospholipase A1 shows a narrow optimum pH at 8.5 -9, while phospholipase A2 activity presents only small variations between pH 7 and 9.5. Towards exogenous phospholipids at the optimum pH 8.5 of phospholipase A1, the specific activity of the latter is 3-fold higher than phospholipase A2 specific activity. On the contrary towards endogenous phospholipids, phospolipase A2 activity is higher than phospholipase A2 activity. Moreover labeled endogenous PE hydrolysis by phospholipase A2 is decreased by addition of non labeled exogenous PE into the incubation medium. All these data suggest that the active site of phospholipase A1 is turned to the outside and acts only on exogenous substrates: for phospholipase A2 it would be inside, and exogenous phospholipids could be hydrolyzed only after penetrating the membrane."}
{"id": "PMID:8156", "title": "[Kinetics of Ca 2+ or Mg 2+ activated ATPase from lymphocyte plasma membranes].", "content": "The kinetic study of the C2+ ATPase activity of lymphocyte plasma memebranes allowed some properties of this enzyme to be evidenced. The Ca2+-activated hydrolysis of ATP is independent of a non-specific alkaline phosphatase. The substrate of the ATPase activity is the chelate Ca2+- ATP. Mg2+ may substitute for Ca2+ both as chelating ion and as activating ion. Several results suggest that we have only one ATPase, activated either by Ca2+-, or by Mg2+ with less efficiency; both chelates hve the same Km; pH values for maximum activity and transition temperatures are identical; the effects of free ions are also the same, activation at low concentration and inhibition at high concentration.", "contents": "[Kinetics of Ca 2+ or Mg 2+ activated ATPase from lymphocyte plasma membranes]. The kinetic study of the C2+ ATPase activity of lymphocyte plasma memebranes allowed some properties of this enzyme to be evidenced. The Ca2+-activated hydrolysis of ATP is independent of a non-specific alkaline phosphatase. The substrate of the ATPase activity is the chelate Ca2+- ATP. Mg2+ may substitute for Ca2+ both as chelating ion and as activating ion. Several results suggest that we have only one ATPase, activated either by Ca2+-, or by Mg2+ with less efficiency; both chelates hve the same Km; pH values for maximum activity and transition temperatures are identical; the effects of free ions are also the same, activation at low concentration and inhibition at high concentration."}
{"id": "PMID:8157", "title": "The reaction of the histidine residues of luteinizing hormone with ethoxyformyl anhydride.", "content": "Bovine and porcine luteinizing hormones (B-LH, P-LH) and their subunits were treated by ethoxyformyl anhydride. The acylation of the histidine residues was followed by examination of the absorbance spectrum. All the histidine residues of the luteinizing hormone molecule can be modified at pH5. However 2 His in B-LH and 1 in P-LH appear to be much less reactive at pH 5 than the others and their acylated imidazols more labile at the same pH. At neutral pH, 2 histidines in B-LH (and 1 in P-LH) become unreactive. In the case of the subunits, 1 histidine becomes unreactive in each subunit at neutral pH. These unreactive histidine residues at neutral pH are probably those which appear to be poorly reactive at pH 5. Comparison of the results obtained with B-LH and P-LH suggests that of the 2 histidine residues present in B-LH and absent in P-LH (beta 60, beta 112), only one exhibits a low reactivity. Acylation of 4 His in B-LH do not cause dissociation into subunits of the molecule but supress 95 per cent of the biological activity.", "contents": "The reaction of the histidine residues of luteinizing hormone with ethoxyformyl anhydride. Bovine and porcine luteinizing hormones (B-LH, P-LH) and their subunits were treated by ethoxyformyl anhydride. The acylation of the histidine residues was followed by examination of the absorbance spectrum. All the histidine residues of the luteinizing hormone molecule can be modified at pH5. However 2 His in B-LH and 1 in P-LH appear to be much less reactive at pH 5 than the others and their acylated imidazols more labile at the same pH. At neutral pH, 2 histidines in B-LH (and 1 in P-LH) become unreactive. In the case of the subunits, 1 histidine becomes unreactive in each subunit at neutral pH. These unreactive histidine residues at neutral pH are probably those which appear to be poorly reactive at pH 5. Comparison of the results obtained with B-LH and P-LH suggests that of the 2 histidine residues present in B-LH and absent in P-LH (beta 60, beta 112), only one exhibits a low reactivity. Acylation of 4 His in B-LH do not cause dissociation into subunits of the molecule but supress 95 per cent of the biological activity."}
{"id": "PMID:8159", "title": "[Spectroscopic study of the structural changes of scorpion hemocyanin, induced by pH variations and addition of various salts].", "content": "Structural modifications of the scorpion haemocyanin induced by pH variations and salt addition are studied by U.V. absorption, fluorescence, circular dichroism and light scattering. Haemocyanin fluorescence is due to both aromatic amino-acids tyrosine and tryptophan. Deoxygenation or denaturation lead to a fourfold enhancement of its intensity. At acidic pH the active site is modified and the protein is dissociated, but at alkaline pH the haemocyanin aggregates. The addition of different salts (sodium citrate, potassium bromide and iodide...) involves protein dissociation, the amplitude of which depends on the anion. But pH variations and salt addition don't change the haemocyanin secondary structure as shown by circular dichroism. The C.D. spectrum of scorpion haemocyanin exhibits the characteristic bands of Arthropod haemocyanine.", "contents": "[Spectroscopic study of the structural changes of scorpion hemocyanin, induced by pH variations and addition of various salts]. Structural modifications of the scorpion haemocyanin induced by pH variations and salt addition are studied by U.V. absorption, fluorescence, circular dichroism and light scattering. Haemocyanin fluorescence is due to both aromatic amino-acids tyrosine and tryptophan. Deoxygenation or denaturation lead to a fourfold enhancement of its intensity. At acidic pH the active site is modified and the protein is dissociated, but at alkaline pH the haemocyanin aggregates. The addition of different salts (sodium citrate, potassium bromide and iodide...) involves protein dissociation, the amplitude of which depends on the anion. But pH variations and salt addition don't change the haemocyanin secondary structure as shown by circular dichroism. The C.D. spectrum of scorpion haemocyanin exhibits the characteristic bands of Arthropod haemocyanine."}
{"id": "PMID:8163", "title": "pH and the level of calcium in the blood of fetal and neonatal albino rats.", "content": "Near-term rat fetuses in utero are acidotic and hypoxic, and have high levels of total serum calcium. In the first hour of postnatal life, pO2 and pH increase and pCO2 and calcium fall. Between 1 and 4 h following birth, respiratory gases vary little, whereas pH continues to rise and calcium further declines. By 4 h, newborns reach normal pH levels but are markedly hypocalcemic. It is suggested that the 'hypercalcemia' of intrauterine life is related to acidosis in utero, and that following birth, the initial fall in serum calcium is associated with the blowing off of CO2 and a concomitant rise in pH. The later decline in circulating calcium is independent of alterations in respiratory gases and relates directly to the final correction of neonatal acidosis.", "contents": "pH and the level of calcium in the blood of fetal and neonatal albino rats. Near-term rat fetuses in utero are acidotic and hypoxic, and have high levels of total serum calcium. In the first hour of postnatal life, pO2 and pH increase and pCO2 and calcium fall. Between 1 and 4 h following birth, respiratory gases vary little, whereas pH continues to rise and calcium further declines. By 4 h, newborns reach normal pH levels but are markedly hypocalcemic. It is suggested that the 'hypercalcemia' of intrauterine life is related to acidosis in utero, and that following birth, the initial fall in serum calcium is associated with the blowing off of CO2 and a concomitant rise in pH. The later decline in circulating calcium is independent of alterations in respiratory gases and relates directly to the final correction of neonatal acidosis."}
{"id": "PMID:8164", "title": "Nasal continuous positive airway pressure. Improvement in arterial oxygenation in hyaline membrane disease.", "content": "Continuous positive airway pressure (CPAP) was employed using nasal prongs in 30 neonates with hyaline membrane disease (HMD). There was a significant improvement in mean PaO2 (from 47 to 80 mmHg;p less than 0.001) with no significant change in PaCO2 or pH within a mean 36 min of therapy. Use of the technique allowed reduction of FiO2 to less than 0.60 in less than 20 h in 18 infants. Infants treated within 24 h of birth had significantly greater improvements in PaO2. Complications were infrequent and only 3 of 30 babies developed a pneumothorax while on nasal CPAP. Only 1 of the 23 survivors required mechanical ventilation in addition to nasal CPAP.", "contents": "Nasal continuous positive airway pressure. Improvement in arterial oxygenation in hyaline membrane disease. Continuous positive airway pressure (CPAP) was employed using nasal prongs in 30 neonates with hyaline membrane disease (HMD). There was a significant improvement in mean PaO2 (from 47 to 80 mmHg;p less than 0.001) with no significant change in PaCO2 or pH within a mean 36 min of therapy. Use of the technique allowed reduction of FiO2 to less than 0.60 in less than 20 h in 18 infants. Infants treated within 24 h of birth had significantly greater improvements in PaO2. Complications were infrequent and only 3 of 30 babies developed a pneumothorax while on nasal CPAP. Only 1 of the 23 survivors required mechanical ventilation in addition to nasal CPAP."}
{"id": "PMID:8165", "title": "Lung lecithin biosynthesis in the nonhuman primate fetus: determination of the primary pathway in vivo.", "content": "The two pathways for de novo lecithin (phosphatidylcholine) biosynthesis, choline incorporation (1) and phosphatidylethanolamine methylation (II), were examined simultaneously in lung and other tissues of Rhesus monkey fetuses. Cannulation of interplacental fetal vessels permitted studies on the intrauterine fetus without disruption of fetal-placental-maternal-amniotic fluid anatomic integrity. In contrast to observations with indirect techniques in the same species, direct measurement of the incorporation of isotopic precursors (3H-choline and 14C-ethanolamine) into lecithin indicated that pathway I predominates by 100-fold over PE methylation in pulmonary lecithin synthesis. Fetal liver, brain, and kidney also showed 10--70-gold greater choline incorporation that methylation activity. Measurement of lung phosphatidylcholine production via the two pathways in acidemic fetuses (umbilical venous pH less than 7.20) demonstrated marked inhibition of pathway I, but not II. It is concluded that the choline pathway is the major mechanism of lung lecithin synthesis in fetal primates and that this pathway is pH sensitive in vivo.", "contents": "Lung lecithin biosynthesis in the nonhuman primate fetus: determination of the primary pathway in vivo. The two pathways for de novo lecithin (phosphatidylcholine) biosynthesis, choline incorporation (1) and phosphatidylethanolamine methylation (II), were examined simultaneously in lung and other tissues of Rhesus monkey fetuses. Cannulation of interplacental fetal vessels permitted studies on the intrauterine fetus without disruption of fetal-placental-maternal-amniotic fluid anatomic integrity. In contrast to observations with indirect techniques in the same species, direct measurement of the incorporation of isotopic precursors (3H-choline and 14C-ethanolamine) into lecithin indicated that pathway I predominates by 100-fold over PE methylation in pulmonary lecithin synthesis. Fetal liver, brain, and kidney also showed 10--70-gold greater choline incorporation that methylation activity. Measurement of lung phosphatidylcholine production via the two pathways in acidemic fetuses (umbilical venous pH less than 7.20) demonstrated marked inhibition of pathway I, but not II. It is concluded that the choline pathway is the major mechanism of lung lecithin synthesis in fetal primates and that this pathway is pH sensitive in vivo."}
{"id": "PMID:8166", "title": "2,3-2, 3-.", "content": "Erythrocityc variations of glycolytic intermediates and 2,3-DPG levels in rabbits performing strenuous exercise under hypoxic conditions are correlated with blood pH variations. The hypoxia alone is not able to induce directly an increase of erythrocytic 2,3-DPG level which would facilitate tissue oxygenation.", "contents": "2,3-2, 3-. Erythrocityc variations of glycolytic intermediates and 2,3-DPG levels in rabbits performing strenuous exercise under hypoxic conditions are correlated with blood pH variations. The hypoxia alone is not able to induce directly an increase of erythrocytic 2,3-DPG level which would facilitate tissue oxygenation."}
{"id": "PMID:8167", "title": "Electrostatic interactions at charged lipid membranes. I. Effects of pH and univalent cations on membrane structure.", "content": "Electrostatic interactions at charged lipid membranes make a significant contribution to the free energy of the system, and can be varied within a wide range by alteration either of the membrane's surface charge density or of the concentration of electrolytes in the surrounding medium. Changes in the charged membrane's structure, such as the ordered in equilibrium fluid phase transition, can thus be induced at constant temperature by variations in pH and salt concentration. An adequate quantitative description of these phenomena is obtained from the Gouy--Chapman theory. The good agreement between theory and experiment confirms that the expression derived for the electrostatic free energy especially in respect of its positive sign is correct. The classical expression derived for the electrostatic free energy, especially in respect of its positive sign, is correct. The classical expression for the \"free energy of the double layer\" derived by Verwey and Overbeek, which has a negative sign, is not applicable to lipid membranes with ionizable polar groups.", "contents": "Electrostatic interactions at charged lipid membranes. I. Effects of pH and univalent cations on membrane structure. Electrostatic interactions at charged lipid membranes make a significant contribution to the free energy of the system, and can be varied within a wide range by alteration either of the membrane's surface charge density or of the concentration of electrolytes in the surrounding medium. Changes in the charged membrane's structure, such as the ordered in equilibrium fluid phase transition, can thus be induced at constant temperature by variations in pH and salt concentration. An adequate quantitative description of these phenomena is obtained from the Gouy--Chapman theory. The good agreement between theory and experiment confirms that the expression derived for the electrostatic free energy especially in respect of its positive sign is correct. The classical expression derived for the electrostatic free energy, especially in respect of its positive sign, is correct. The classical expression for the \"free energy of the double layer\" derived by Verwey and Overbeek, which has a negative sign, is not applicable to lipid membranes with ionizable polar groups."}
{"id": "PMID:8168", "title": "Formation of proteinoid microspheres under simulated prebiotic atmospheres and individual gases.", "content": "The formation of microspheres from acidic and basic proteinoids was attempted under simulated prebiotic atmospheres and constituent gases thereof. Both types of proteinoid yielded microspheres under carbon dioxide, carbon monoxide, methane, hydrogen sulfide, hydrogen, nitrogen, and oxygen (tested separately) and also under nitrogen-carbon dioxide atmospheres; higher proportions of carbon dioxide resulted in fewer spheres from basic proteinoid. Neither type of proteinoid formed spheres on 10-minute exposure to ammonia or methane-hydrogen-ammonia atmospheres. (Brief exposure resulted in spheres from basic proteinoid.) The effects, both qualitative and quantitative, were indicated by control experiments to be due to pH, rather than to the specific gas (or ion). The results suggest that the proteinoid microsphere model for protocells is applicable under a variety of possible prebiotic atmospheres, with some restrictions imposed by pH.", "contents": "Formation of proteinoid microspheres under simulated prebiotic atmospheres and individual gases. The formation of microspheres from acidic and basic proteinoids was attempted under simulated prebiotic atmospheres and constituent gases thereof. Both types of proteinoid yielded microspheres under carbon dioxide, carbon monoxide, methane, hydrogen sulfide, hydrogen, nitrogen, and oxygen (tested separately) and also under nitrogen-carbon dioxide atmospheres; higher proportions of carbon dioxide resulted in fewer spheres from basic proteinoid. Neither type of proteinoid formed spheres on 10-minute exposure to ammonia or methane-hydrogen-ammonia atmospheres. (Brief exposure resulted in spheres from basic proteinoid.) The effects, both qualitative and quantitative, were indicated by control experiments to be due to pH, rather than to the specific gas (or ion). The results suggest that the proteinoid microsphere model for protocells is applicable under a variety of possible prebiotic atmospheres, with some restrictions imposed by pH."}
{"id": "PMID:8169", "title": "Continuous regeneration of NAD(P)+ by flavins covalently bound to sepharose.", "content": "Various flavins, FMN, FAD, and acriflavin, were immobilized to Sepharose using several different coupling methods. The only product stable enough to permit extended studies was acriflavin coupled to epoxy-substituted Sepharose. The nonenzymic oxidizing capacity towards NAD(P) H was investigated and a 25% specific activity, compared to that of free acriflavin, was observed. The reduced acriflavin was immediately auto-reoxidized in air and could thus be reused. It was shown that acriflavin-Sepharose preparations function as NAD(P)H oxidizing agents in a number of different dehydrogenase systems including lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH), malate dehydrogenase (MDH), alanine dehydrogenase (alaDH), and glutamate dehydrogenase (GDH). The amount of expensive coenzyme necessary for high product formation of such systems was thereby markedly reduced.", "contents": "Continuous regeneration of NAD(P)+ by flavins covalently bound to sepharose. Various flavins, FMN, FAD, and acriflavin, were immobilized to Sepharose using several different coupling methods. The only product stable enough to permit extended studies was acriflavin coupled to epoxy-substituted Sepharose. The nonenzymic oxidizing capacity towards NAD(P) H was investigated and a 25% specific activity, compared to that of free acriflavin, was observed. The reduced acriflavin was immediately auto-reoxidized in air and could thus be reused. It was shown that acriflavin-Sepharose preparations function as NAD(P)H oxidizing agents in a number of different dehydrogenase systems including lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH), malate dehydrogenase (MDH), alanine dehydrogenase (alaDH), and glutamate dehydrogenase (GDH). The amount of expensive coenzyme necessary for high product formation of such systems was thereby markedly reduced."}
{"id": "PMID:8174", "title": "[\"Lymph node\" form of graft-versus-host reaction in mice].", "content": "Local type of the graft-versus-host reaction was induced in adult hybrid mice (CBA X C57BL) F1 by the transfer of splenic, thymus and bone marrow CBA cells subcutaneously into the right hind footpad. The weight gain of the regional knee lymph node and blast accumulation in it 7 days later were used as indices of the graft-versus-host activity. After the transfer of 5 and 20 x 10(6) splenic cells the absolute weight of the regional lymph node was 8-10 times higher than that of the contralateral control; it was also significantly greater in comparison with controls which received live syngeneic or semiallogeneic dead cells from the same source. Contrary to controls, in case of the live cells a direct dose-effect dependency could be seen. The lymph node weight gain was accompanied by a regular immunoblast accumulation. The effect of the thymus and the bone marrow cells was less pronounced than that of the splenic cells.", "contents": "[\"Lymph node\" form of graft-versus-host reaction in mice]. Local type of the graft-versus-host reaction was induced in adult hybrid mice (CBA X C57BL) F1 by the transfer of splenic, thymus and bone marrow CBA cells subcutaneously into the right hind footpad. The weight gain of the regional knee lymph node and blast accumulation in it 7 days later were used as indices of the graft-versus-host activity. After the transfer of 5 and 20 x 10(6) splenic cells the absolute weight of the regional lymph node was 8-10 times higher than that of the contralateral control; it was also significantly greater in comparison with controls which received live syngeneic or semiallogeneic dead cells from the same source. Contrary to controls, in case of the live cells a direct dose-effect dependency could be seen. The lymph node weight gain was accompanied by a regular immunoblast accumulation. The effect of the thymus and the bone marrow cells was less pronounced than that of the splenic cells."}
{"id": "PMID:8176", "title": "[Participation of mouse T- and B-lymphocytes in the graft versus host reaction].", "content": "Cells of the spleen or lymph nodes of CBA mice were transplanted to sublethally irradiated (CBAXC57BL/6)F1 mice; this caused development of the graft-versus-host reaction (GVHR). Lymphocytes lost the capacity to realize this reaction after in vitro treatment with specific sera against mouse T- and B-lymphocytes. Apparently, development of the GVHR in mice was connected with the cooperative interaction of T- and B-lymphocytes.", "contents": "[Participation of mouse T- and B-lymphocytes in the graft versus host reaction]. Cells of the spleen or lymph nodes of CBA mice were transplanted to sublethally irradiated (CBAXC57BL/6)F1 mice; this caused development of the graft-versus-host reaction (GVHR). Lymphocytes lost the capacity to realize this reaction after in vitro treatment with specific sera against mouse T- and B-lymphocytes. Apparently, development of the GVHR in mice was connected with the cooperative interaction of T- and B-lymphocytes."}
{"id": "PMID:8177", "title": "[Ribonuclease activity in preparations of human leukocyte interferon].", "content": "Preparations of human leukocyte interferon obtained by multi-stage purification procedure exhibited ribonuclease activity with the optimum at pH 7.0--7.5. The enzyme possessed the endonuclease action mechanism. Most substances studied for their effect on the RNA-ase activity in human interferon preparations showed many of them to act on the enzyme in the same way as on other ribonucleases. However, dithioerythritie, a reducing agent for disulfide bounds, activated the ribonuclease in the interferon preparation, as distinct from the pancreatic ribonuclease, which was inhibited by this preparation. Patterns of protein and RNA-ase distribution were obtained by electrophoresis in polyacrylamide gel.", "contents": "[Ribonuclease activity in preparations of human leukocyte interferon]. Preparations of human leukocyte interferon obtained by multi-stage purification procedure exhibited ribonuclease activity with the optimum at pH 7.0--7.5. The enzyme possessed the endonuclease action mechanism. Most substances studied for their effect on the RNA-ase activity in human interferon preparations showed many of them to act on the enzyme in the same way as on other ribonucleases. However, dithioerythritie, a reducing agent for disulfide bounds, activated the ribonuclease in the interferon preparation, as distinct from the pancreatic ribonuclease, which was inhibited by this preparation. Patterns of protein and RNA-ase distribution were obtained by electrophoresis in polyacrylamide gel."}
{"id": "PMID:8178", "title": "[Genetic differences in lymphoid tissue reactivity during liver regeneration in mice of different lines].", "content": "The transfer of lymphocytes together with sheep erythrocytes from partially hepatectomized mice to syngenous lethally irradiated mice (CAB and C57BL) increased the number of antibody forming cells in the recipient's spleen. The lymphocytes of CBA mice acquired this ability much earlier after the operation (in 4 hours) than those of the C57BL mice (in 17 hours). After the transfer of lymphocytes in the semisyngenous system there was a decrease of antibody forming cells during subsequent recipient's immunization with sheep erythrocytes; this was the result of the graft versus host reaction. The latter reaction was less marked in the operated than in control mice. These changes also occurred earlier after the operation in the CBA than in C57BL mice.", "contents": "[Genetic differences in lymphoid tissue reactivity during liver regeneration in mice of different lines]. The transfer of lymphocytes together with sheep erythrocytes from partially hepatectomized mice to syngenous lethally irradiated mice (CAB and C57BL) increased the number of antibody forming cells in the recipient's spleen. The lymphocytes of CBA mice acquired this ability much earlier after the operation (in 4 hours) than those of the C57BL mice (in 17 hours). After the transfer of lymphocytes in the semisyngenous system there was a decrease of antibody forming cells during subsequent recipient's immunization with sheep erythrocytes; this was the result of the graft versus host reaction. The latter reaction was less marked in the operated than in control mice. These changes also occurred earlier after the operation in the CBA than in C57BL mice."}
{"id": "PMID:8179", "title": "[Distribution of lysosomal enzyme activity in cells of the renal cortical substance following transplantation of allogenic spleen cells under its capsule].", "content": "Allogenous spleen cells were transplanted subcapsularly into the kidney of mice irradiated in a dose of 650 r. The resulting damage of the kidney cortex structure was closely associated with the function of macrophages and with activation of the lysosomal enzymes.", "contents": "[Distribution of lysosomal enzyme activity in cells of the renal cortical substance following transplantation of allogenic spleen cells under its capsule]. Allogenous spleen cells were transplanted subcapsularly into the kidney of mice irradiated in a dose of 650 r. The resulting damage of the kidney cortex structure was closely associated with the function of macrophages and with activation of the lysosomal enzymes."}
{"id": "PMID:8180", "title": "Successful bone marrow transplantation against mixed lymphocyte culture barrier.", "content": "If bone marrow transplantation is to become widely applicable in the treatment of patients with leukemia and aplastic anemia, the necessity to have a perfectly histocompatible donor must be overcome. In an effort to define the roles of HL-A type and mixed lymphocyte culture (MLC) reactivity in the determination of successful engraftment and the occurrence of graftversus-host disease (GVHD), we have attempted transplantation of a child with acute myeloblastic leukemia (AML) using an HL-A identical, MLC-reactive sibling donor. Successful engraftment has been accomplished, as documented by the appearance of multiple donor genetic markers in the recipient. There is no evidence of severe GVHD. The recipient is alive, without evidence of leukemia, and has returned to full activities 9 mo after transplantation. The recipient now produces lymphocytes, which have the MLC reactivity that characterize the donor's lymphocytes, rather than that of her own pretransplant lymphocytes. This experience demonstrates that successful bone marrow transplantation in patients with leukemia can be accomplished in the face of MLC reactivity.", "contents": "Successful bone marrow transplantation against mixed lymphocyte culture barrier. If bone marrow transplantation is to become widely applicable in the treatment of patients with leukemia and aplastic anemia, the necessity to have a perfectly histocompatible donor must be overcome. In an effort to define the roles of HL-A type and mixed lymphocyte culture (MLC) reactivity in the determination of successful engraftment and the occurrence of graftversus-host disease (GVHD), we have attempted transplantation of a child with acute myeloblastic leukemia (AML) using an HL-A identical, MLC-reactive sibling donor. Successful engraftment has been accomplished, as documented by the appearance of multiple donor genetic markers in the recipient. There is no evidence of severe GVHD. The recipient is alive, without evidence of leukemia, and has returned to full activities 9 mo after transplantation. The recipient now produces lymphocytes, which have the MLC reactivity that characterize the donor's lymphocytes, rather than that of her own pretransplant lymphocytes. This experience demonstrates that successful bone marrow transplantation in patients with leukemia can be accomplished in the face of MLC reactivity."}
{"id": "PMID:8184", "title": "Comparison of atenolol and propranolol during insulin-induced hypoglycaemia.", "content": "The effects of atenolol, a new beta1-blocking drug, on pulse rate, sweating, and blood glucose levels during insulin-induced hypoglycaemia were studied in a double-blind crossover trial in eight normal subjects using placebo and propranolol as reference agents. The intensity of induced hypoglycaemia was identical for atenolol, propranolol, and placebo. Propranolol prolonged hypoglycaemia, but atenolol did not. Atenolol may therefore be safe for use in patients receiving insulin.", "contents": "Comparison of atenolol and propranolol during insulin-induced hypoglycaemia. The effects of atenolol, a new beta1-blocking drug, on pulse rate, sweating, and blood glucose levels during insulin-induced hypoglycaemia were studied in a double-blind crossover trial in eight normal subjects using placebo and propranolol as reference agents. The intensity of induced hypoglycaemia was identical for atenolol, propranolol, and placebo. Propranolol prolonged hypoglycaemia, but atenolol did not. Atenolol may therefore be safe for use in patients receiving insulin."}
{"id": "PMID:8187", "title": "Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia.", "content": "Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus.", "contents": "Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia. Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus."}
{"id": "PMID:8188", "title": "Effect of atenolol on ventilatory and cardiac function in asthma.", "content": "The effects on ventilatory and cardiac function of atenolol, a new cardioselective beta-adrenoceptor blocking agent, were compared with those of practolol in a double-blind trial in 12 patients with asthma. Both drugs impaired ventilatory function--atenolol insignificantly and practolol significantly. Atenolol was if anything more cardioselective than practolol. Neither drug interfered significantly with the bronchodilator response to inhaled isoprenaline. Atenolol is suitable for use in patients for whom practolol would formerly have been chosen because of its cardioselectivity.", "contents": "Effect of atenolol on ventilatory and cardiac function in asthma. The effects on ventilatory and cardiac function of atenolol, a new cardioselective beta-adrenoceptor blocking agent, were compared with those of practolol in a double-blind trial in 12 patients with asthma. Both drugs impaired ventilatory function--atenolol insignificantly and practolol significantly. Atenolol was if anything more cardioselective than practolol. Neither drug interfered significantly with the bronchodilator response to inhaled isoprenaline. Atenolol is suitable for use in patients for whom practolol would formerly have been chosen because of its cardioselectivity."}
{"id": "PMID:8192", "title": "Light-evoked release of glycine from cat and rabbit retina.", "content": "The light-evoked release of [3H]glycine from retina in cat (in vivo) after pre-retinal perfusion and in rabbit (in vitro) after intravitreal injection was studied. The site of uptake of [3H]glycine into retina was checked by autoradiography and was found to be almost exclusively in a type of amacrine cells. If the retina loaded with [3H]glycine was stimulated by light flashes the release increased significantly in both in vivo and in vitro experiments. When the flashing light was exchanged for continuous light there was not change in the spontaneous efflux of radioactivity. Chromatographic experiments showed that the main part of the radioactivity released by light was glycine. The light-evoked release of glycine from retina was dependent on temperature and Ca2+. Low temperature (+2 to +4 degrees C) abolished the increased release. If Ca2+ was ommitted from the perfusion medium and EDTA was added there was no light-inducable change in the efflux of radioactivity in retinas loaded with [3H]valine. The present results, that light stimulation will release glycine from the retina both in vivo and in vitro, are further criterion for it as neurotransmitter.", "contents": "Light-evoked release of glycine from cat and rabbit retina. The light-evoked release of [3H]glycine from retina in cat (in vivo) after pre-retinal perfusion and in rabbit (in vitro) after intravitreal injection was studied. The site of uptake of [3H]glycine into retina was checked by autoradiography and was found to be almost exclusively in a type of amacrine cells. If the retina loaded with [3H]glycine was stimulated by light flashes the release increased significantly in both in vivo and in vitro experiments. When the flashing light was exchanged for continuous light there was not change in the spontaneous efflux of radioactivity. Chromatographic experiments showed that the main part of the radioactivity released by light was glycine. The light-evoked release of glycine from retina was dependent on temperature and Ca2+. Low temperature (+2 to +4 degrees C) abolished the increased release. If Ca2+ was ommitted from the perfusion medium and EDTA was added there was no light-inducable change in the efflux of radioactivity in retinas loaded with [3H]valine. The present results, that light stimulation will release glycine from the retina both in vivo and in vitro, are further criterion for it as neurotransmitter."}
{"id": "PMID:8194", "title": "Osteopetrosis of microphthalmic mice -- a defect of the hematopoietic stem cell.?", "content": "The recessive genes mi and gl in the homozygous state determine, among other phenotypic effects, osteopetrosis in the house mouse. From a stock carrying mi derived from Gr\u00fcneberg (1963) the mi gene was bred into the standard CBA/H inbred strain. Microphthalmic mice of these two stocks and their hybrids were treated as newborn by intraperitoneal injection and at weaning or maturity by intravenous injection of cell suspensions containing hematopoietic stem cells from phenotypically normal mice. Resolution of much of the osteopetrosis but not the other phenotypic effects occurred within a few months in the majority of cases, provided syngeneic or H-2 compatible allogeneic cells were given: it did not occur spontaneously or on giving H-2 incompatible cells or on giving compatible material by an inappropriate route. The results accord with hypotheses that (1) osteoclasis of scaffoldtype woven bone is impaired in mi mi, (2) that osteoclastic cells are derived through circulating monocytes from hematopoietic stem cells, and (3) in mi mi this defect can be overcome by a transplant of normal hemopoietic stem cells.", "contents": "Osteopetrosis of microphthalmic mice -- a defect of the hematopoietic stem cell.? The recessive genes mi and gl in the homozygous state determine, among other phenotypic effects, osteopetrosis in the house mouse. From a stock carrying mi derived from Gr\u00fcneberg (1963) the mi gene was bred into the standard CBA/H inbred strain. Microphthalmic mice of these two stocks and their hybrids were treated as newborn by intraperitoneal injection and at weaning or maturity by intravenous injection of cell suspensions containing hematopoietic stem cells from phenotypically normal mice. Resolution of much of the osteopetrosis but not the other phenotypic effects occurred within a few months in the majority of cases, provided syngeneic or H-2 compatible allogeneic cells were given: it did not occur spontaneously or on giving H-2 incompatible cells or on giving compatible material by an inappropriate route. The results accord with hypotheses that (1) osteoclasis of scaffoldtype woven bone is impaired in mi mi, (2) that osteoclastic cells are derived through circulating monocytes from hematopoietic stem cells, and (3) in mi mi this defect can be overcome by a transplant of normal hemopoietic stem cells."}
{"id": "PMID:8195", "title": "Metabolism of (4-14C)estrone by sheep erythrocytes around the time of parturition.", "content": "The metabolism of [4-14C]estrone in vitro by red blood cells of sheep in late pregnancy and after partuirition has been studied. [14C]estrone (600 ng) was incubated with 0.5 ml erythrocytes plus 0.5 ml of Krebs-Ringer phosphate buffer, pH 7.4, for 2 h at 37 degrees C in an atmosphere of air. After incubation, [3H]estrogens were added to the incubation medium as internal standards for identification and for correction for procedural losses. Metabolites were isolated and purified by chromatography, acetate derivative formation, and recrystallization to a constant 3H/14C ratio. Approximately 20% and 2% of added estrone were converted to 17beta-estradiol and 17 alpha-estradiol, respectively. The remainder was recovered unchanged. Daily measurements of 17 beta-hydroxysteroid dehydrogenase activity in erythrocytes of five ewes, over the period 8 days prepartum to 4 days postpartum, showed no significant change in activity.", "contents": "Metabolism of (4-14C)estrone by sheep erythrocytes around the time of parturition. The metabolism of [4-14C]estrone in vitro by red blood cells of sheep in late pregnancy and after partuirition has been studied. [14C]estrone (600 ng) was incubated with 0.5 ml erythrocytes plus 0.5 ml of Krebs-Ringer phosphate buffer, pH 7.4, for 2 h at 37 degrees C in an atmosphere of air. After incubation, [3H]estrogens were added to the incubation medium as internal standards for identification and for correction for procedural losses. Metabolites were isolated and purified by chromatography, acetate derivative formation, and recrystallization to a constant 3H/14C ratio. Approximately 20% and 2% of added estrone were converted to 17beta-estradiol and 17 alpha-estradiol, respectively. The remainder was recovered unchanged. Daily measurements of 17 beta-hydroxysteroid dehydrogenase activity in erythrocytes of five ewes, over the period 8 days prepartum to 4 days postpartum, showed no significant change in activity."}
{"id": "PMID:8196", "title": "[Biosynthesis of glycoproteins in pulmonary parenchyma. II. Galactosyltransferase activity in pneumocyte subcellular fractions].", "content": "A soluble galactosyltransferase exists in the cell sap of the alveolar cells of the lung. The optimal conditions of galactosyltransferase are: pH 6, 20 DEGREES C, 10 mM Mn2+, 1 mM Mg2+. Michaelis constant for substrate UDP-galactose is 390 nM. By electrofocusing on Ampholine column, galactosyltransferase appears in a unique peak, at pHi 4.8. The parameters of the purified enzyme are the same as that of the crude enzyme. UDP is a noncompetitive inhibitor for the purified enzyme.", "contents": "[Biosynthesis of glycoproteins in pulmonary parenchyma. II. Galactosyltransferase activity in pneumocyte subcellular fractions]. A soluble galactosyltransferase exists in the cell sap of the alveolar cells of the lung. The optimal conditions of galactosyltransferase are: pH 6, 20 DEGREES C, 10 mM Mn2+, 1 mM Mg2+. Michaelis constant for substrate UDP-galactose is 390 nM. By electrofocusing on Ampholine column, galactosyltransferase appears in a unique peak, at pHi 4.8. The parameters of the purified enzyme are the same as that of the crude enzyme. UDP is a noncompetitive inhibitor for the purified enzyme."}
{"id": "PMID:8197", "title": "The influence of beta-adrenergic antagonists on the adrenergic responses of the rat vas deferens.", "content": "The influence of beta-adrenergic antagonists (propranolol, pronethalol, alprenolol, isopropylmethoxamine, H 35/25, sotalol and practolol) on isotonic contractile responses to norepinephrine (NE) was studies. All drugs caused an increase in the maximum responses while depressant effects were seen only with high doses of propranolol, pronethalol and alprenolol. The enhancement of responses to NE was considerably greater at low concentrations of calcium (0.5-1.0 mM) than at high (8 mM) concentrations. The inhibitory effects of propranolol, pronethalol and alprenolol were diminished but not completely overcome by increasing calcium concentrations form 1.8 to 8 mM. Cumulative dose-response curves of calcium showed no increase in maximum responses although responses to low concentrations of calcium were augmented by sotalol and practolol. Evidence suggests that the enhancing effects of these drugs may be due to their facilitatory effect on calcium mobilization following alpha-adrenoceptor activation while their depressant properties probably reflect their membrane stabilizing properties.", "contents": "The influence of beta-adrenergic antagonists on the adrenergic responses of the rat vas deferens. The influence of beta-adrenergic antagonists (propranolol, pronethalol, alprenolol, isopropylmethoxamine, H 35/25, sotalol and practolol) on isotonic contractile responses to norepinephrine (NE) was studies. All drugs caused an increase in the maximum responses while depressant effects were seen only with high doses of propranolol, pronethalol and alprenolol. The enhancement of responses to NE was considerably greater at low concentrations of calcium (0.5-1.0 mM) than at high (8 mM) concentrations. The inhibitory effects of propranolol, pronethalol and alprenolol were diminished but not completely overcome by increasing calcium concentrations form 1.8 to 8 mM. Cumulative dose-response curves of calcium showed no increase in maximum responses although responses to low concentrations of calcium were augmented by sotalol and practolol. Evidence suggests that the enhancing effects of these drugs may be due to their facilitatory effect on calcium mobilization following alpha-adrenoceptor activation while their depressant properties probably reflect their membrane stabilizing properties."}
{"id": "PMID:8198", "title": "Effect of hypothyroidism on responsiveness to beta-adrenergic stimulation.", "content": "Chronic administration of aminotriazole (0.5 g/kg food) to rats was accompanied by a reduced responsiveness to acute administration of the beta-adrenergic agonist, l-isoproterenol (50-100 mug/kg, sc). The responses tested included water intake, change in heart rate in the anesthetized and unanesthetized rat, change in mean blood pressure, and change in blood glucose concentration. In addition, the increase in tail skin temperature accompanying administration of epinephrine (1 mg/kg, sc) was significantly reduced in the hypothyroid group. Administration of l-thyroxine (25 mug/kg per day, ip) to aminotriazole-treated rats prevented the reduction in responsiveness to beta-adrenergic stimulation. Thus, an interaction appears to exist between the level of thyroid activity and responsiveness to beta-adrenergic agonists in rats.", "contents": "Effect of hypothyroidism on responsiveness to beta-adrenergic stimulation. Chronic administration of aminotriazole (0.5 g/kg food) to rats was accompanied by a reduced responsiveness to acute administration of the beta-adrenergic agonist, l-isoproterenol (50-100 mug/kg, sc). The responses tested included water intake, change in heart rate in the anesthetized and unanesthetized rat, change in mean blood pressure, and change in blood glucose concentration. In addition, the increase in tail skin temperature accompanying administration of epinephrine (1 mg/kg, sc) was significantly reduced in the hypothyroid group. Administration of l-thyroxine (25 mug/kg per day, ip) to aminotriazole-treated rats prevented the reduction in responsiveness to beta-adrenergic stimulation. Thus, an interaction appears to exist between the level of thyroid activity and responsiveness to beta-adrenergic agonists in rats."}
{"id": "PMID:8199", "title": "Effects of alpha-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs.", "content": "The alpha-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 mug kg-1 min-1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic throacic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265+/56 (SEM) to 370+/65 muequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distalsodium load did not change significantly. In normal dogs, tubular sodium reabsorption decreased significantly from 73.4+/2.8% to 63.1+/4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of alpha-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased alpha-adrenergic activity does not play a significant role in the sodium retention of these animals.", "contents": "Effects of alpha-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs. The alpha-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 mug kg-1 min-1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic throacic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265+/56 (SEM) to 370+/65 muequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distalsodium load did not change significantly. In normal dogs, tubular sodium reabsorption decreased significantly from 73.4+/2.8% to 63.1+/4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of alpha-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased alpha-adrenergic activity does not play a significant role in the sodium retention of these animals."}
{"id": "PMID:8200", "title": "Effects of catecholamines injected into the septal area of the rat brain on natriuresis, kaliuresis and diuresis.", "content": "Urinary output of Na+ and K+, and volume of urine have been studied in conscious, unrestrained, water-loaded male rats following the intraseptal injection of catecholamines. Natriuresis and kaliuresis increased after injecting noradrenaline (NA), the intensity being dose related. The dose-response curve suggests that a monomolecular interacting takes place between NA and pharmacological receptors present in the septal area. No change was observed in diuresis. Systematic mapping of the septal area yielded about the same results for all sites except a zone located in the lateral nucleus that was more sensitive. An alpha blocker (dibenamine), injected intraseptally before NA, showed an inhibitory effect while a beta blocker (propranolol) yielded a potentiation effect. These same effects of the blocking agents were observed when adrenaline was used instead of NA. Lidocaine, which inhibits the re-uptake of NA, showed an enhancement of the natriuretic and kaliuretic effect of NA, and the same effect was observed when the enzymatic destruction of NA was prevented by nialamide, an inhibitor of monoaminoxidase. Dopamine showed a natriuretic effect, but no effect was observed on K+ and urine output. Serotonin had no action on natriuresis, kaliuresis and diuresis.", "contents": "Effects of catecholamines injected into the septal area of the rat brain on natriuresis, kaliuresis and diuresis. Urinary output of Na+ and K+, and volume of urine have been studied in conscious, unrestrained, water-loaded male rats following the intraseptal injection of catecholamines. Natriuresis and kaliuresis increased after injecting noradrenaline (NA), the intensity being dose related. The dose-response curve suggests that a monomolecular interacting takes place between NA and pharmacological receptors present in the septal area. No change was observed in diuresis. Systematic mapping of the septal area yielded about the same results for all sites except a zone located in the lateral nucleus that was more sensitive. An alpha blocker (dibenamine), injected intraseptally before NA, showed an inhibitory effect while a beta blocker (propranolol) yielded a potentiation effect. These same effects of the blocking agents were observed when adrenaline was used instead of NA. Lidocaine, which inhibits the re-uptake of NA, showed an enhancement of the natriuretic and kaliuretic effect of NA, and the same effect was observed when the enzymatic destruction of NA was prevented by nialamide, an inhibitor of monoaminoxidase. Dopamine showed a natriuretic effect, but no effect was observed on K+ and urine output. Serotonin had no action on natriuresis, kaliuresis and diuresis."}
{"id": "PMID:8201", "title": "Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats.", "content": "The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA-NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA-NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.", "contents": "Critical opening pressure and reactivity of tail vessels in conscious hypertensive rats. The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA-NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA-NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA-NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP."}
{"id": "PMID:8202", "title": "Effects of isoproterenol on cyclic-AMP metabolism in rat ventral prostate.", "content": "Beta-Adrenergic stimulation of the ventral prostate cyclic-AMP system was investigated by examining the influence of isoproterenol on endogenous cyclic-AMP levels as well as on the activities of adenylate cyclase CEC 4.6.1.1) and cyclic-AMP-dependent and independent protein kinases (EC 2.7.1.37). Administration of isoproterenol (1 mg/kg, ip) resulted in rapid elevation of adenylate cyclase activity (119%) and cyclic-AMP levels (593%). The observed isoproterenol-stimulated changes in cyclic-AMP metabolism of the ventral prostate were time-dependent and maximal stimulation was seen 5 min after treatment with this beta-adrenergic agonist. The increases in prostatic adenylate cyclase and cyclic-AMP also were related to the dose of isoproterenol administered and maximal enhancement of these parameters was seen with 1 mg/kg dose of the agonist. Whereas pretreatment of rats with propranolol (3mg/kg, ip) partially reversed these alterations, administration of an alpha-adrenergic antagonist, phentolamine, even at a dose of 5 mg/kg, failed to elicit any appreciable effect. Stimulation of prostatic soluble protein kinase by isoproterenol was associated with a decrease (33%) in the activity of the cyclic-AMP-dependent protein kinase with a concomitant increase (25%) in that of the independent enzyme. Whereas the ability of the enzyme to bind cyclic-(3H) AMP in vitro was decreased (54%) following isoproterenol treatment, the protein kinase activity ratio (-cyclic-AMP/+cyclic AMP) was significantly elevated from 0.51+/0.05 to 0.95+/0.08. Although propranolol alone had little or no effect on these parameters, it inhibited partially the isoproterenol-induced alterations in cyclic-AMP-dependent protein kinase and the cyclic-AMP binding capacity. Treatment with propranolol also blocked the increases in the kinase activity ratio and in the activity of cyclic-AMP-independent enzyme seen with isoproterenol. Data suggest that the concentration of ventral prostate cyclic-AMP  as well as the activities of adenylate cyclase and cyclic-AMP-dependent and independent form of protein kinases are subject to modulation by beta-adrenergic stimulation.", "contents": "Effects of isoproterenol on cyclic-AMP metabolism in rat ventral prostate. Beta-Adrenergic stimulation of the ventral prostate cyclic-AMP system was investigated by examining the influence of isoproterenol on endogenous cyclic-AMP levels as well as on the activities of adenylate cyclase CEC 4.6.1.1) and cyclic-AMP-dependent and independent protein kinases (EC 2.7.1.37). Administration of isoproterenol (1 mg/kg, ip) resulted in rapid elevation of adenylate cyclase activity (119%) and cyclic-AMP levels (593%). The observed isoproterenol-stimulated changes in cyclic-AMP metabolism of the ventral prostate were time-dependent and maximal stimulation was seen 5 min after treatment with this beta-adrenergic agonist. The increases in prostatic adenylate cyclase and cyclic-AMP also were related to the dose of isoproterenol administered and maximal enhancement of these parameters was seen with 1 mg/kg dose of the agonist. Whereas pretreatment of rats with propranolol (3mg/kg, ip) partially reversed these alterations, administration of an alpha-adrenergic antagonist, phentolamine, even at a dose of 5 mg/kg, failed to elicit any appreciable effect. Stimulation of prostatic soluble protein kinase by isoproterenol was associated with a decrease (33%) in the activity of the cyclic-AMP-dependent protein kinase with a concomitant increase (25%) in that of the independent enzyme. Whereas the ability of the enzyme to bind cyclic-(3H) AMP in vitro was decreased (54%) following isoproterenol treatment, the protein kinase activity ratio (-cyclic-AMP/+cyclic AMP) was significantly elevated from 0.51+/0.05 to 0.95+/0.08. Although propranolol alone had little or no effect on these parameters, it inhibited partially the isoproterenol-induced alterations in cyclic-AMP-dependent protein kinase and the cyclic-AMP binding capacity. Treatment with propranolol also blocked the increases in the kinase activity ratio and in the activity of cyclic-AMP-independent enzyme seen with isoproterenol. Data suggest that the concentration of ventral prostate cyclic-AMP  as well as the activities of adenylate cyclase and cyclic-AMP-dependent and independent form of protein kinases are subject to modulation by beta-adrenergic stimulation."}
{"id": "PMID:8203", "title": "Epinephrine-induced hepatic potassium movements before and after adrenergic blockade.", "content": "The epinephrine-induced loss and subsequent uptake of K+ by the liver was studied by measuring hepatic arterio-venous K+ differences and splanchnic blood flows in anesthetized dogs with chronically implanted portal vein catheters and celiac and superior mesenteric artery flow probes. When epinephrine was administered intraportally, neither alpha- nor beta-adrenergic blockade, singly or in combination, had significant effects upon the hyperkalemic or the hypokalemic phases in either hepatic venous or systemic arterial blood. It was concluded that the movements of K+ into and out of the liver caused by epinephrine are not mediated by the classical adrenergic receptors as defined by inhibition by specific blocking agents.", "contents": "Epinephrine-induced hepatic potassium movements before and after adrenergic blockade. The epinephrine-induced loss and subsequent uptake of K+ by the liver was studied by measuring hepatic arterio-venous K+ differences and splanchnic blood flows in anesthetized dogs with chronically implanted portal vein catheters and celiac and superior mesenteric artery flow probes. When epinephrine was administered intraportally, neither alpha- nor beta-adrenergic blockade, singly or in combination, had significant effects upon the hyperkalemic or the hypokalemic phases in either hepatic venous or systemic arterial blood. It was concluded that the movements of K+ into and out of the liver caused by epinephrine are not mediated by the classical adrenergic receptors as defined by inhibition by specific blocking agents."}
{"id": "PMID:8204", "title": "Blockade of histamine-induced contractions of guinea pig ielum by beta-haloalkylamines.", "content": "In the longitudinal muscle strip of guinea pig ileum phenoxybenzamine (POB) produces a maximum parallel shift of 0.7 log units in the dose-response curve to histamine. In the presence of sodium thiosulfate in the wash fluid the parallel shift whith retention of maximum response increases to about 2 log units, and a similar value is obtained for Nethyl-N-(2-bromoethyl)-1-naphthylamine. The The agent N-ethyl-N- (2-chloroethyl)benzylamine produces a significantly smaller shift of dose-response curve of 1.53 log units before the maximum response becomes depressed. The receptor-specific depression of maximum response produced by higher doses of POB is reversed by sodium thiosulfate and by bovine serum albumin, while the parallel shift in dose-response curve is unaffected by both treatments. These findings may be explained by a hypothesis involving interaction of 2-haloalkylamines at two sites.", "contents": "Blockade of histamine-induced contractions of guinea pig ielum by beta-haloalkylamines. In the longitudinal muscle strip of guinea pig ileum phenoxybenzamine (POB) produces a maximum parallel shift of 0.7 log units in the dose-response curve to histamine. In the presence of sodium thiosulfate in the wash fluid the parallel shift whith retention of maximum response increases to about 2 log units, and a similar value is obtained for Nethyl-N-(2-bromoethyl)-1-naphthylamine. The The agent N-ethyl-N- (2-chloroethyl)benzylamine produces a significantly smaller shift of dose-response curve of 1.53 log units before the maximum response becomes depressed. The receptor-specific depression of maximum response produced by higher doses of POB is reversed by sodium thiosulfate and by bovine serum albumin, while the parallel shift in dose-response curve is unaffected by both treatments. These findings may be explained by a hypothesis involving interaction of 2-haloalkylamines at two sites."}
{"id": "PMID:8205", "title": "Postsplenectomy sepsis due to influenzal viremia and pneumococcemia.", "content": "A 31-year-old man, who had undergone splenectomy 18 months previously because of hereditary spherocytosis, suddenly became ill, with fever, vomiting, epigastric pain and shock, and died 10 hours after the onset of his symptoms. Autopsy showed influenzal viremia, pneumococcemia and bilateral adrenal hemorrhage. The rapid course of the patient's illness emphasizes the serious risk of sepsis for individuals who have had a splenectomy. Anti-influenza immunization in such patients should be considered.", "contents": "Postsplenectomy sepsis due to influenzal viremia and pneumococcemia. A 31-year-old man, who had undergone splenectomy 18 months previously because of hereditary spherocytosis, suddenly became ill, with fever, vomiting, epigastric pain and shock, and died 10 hours after the onset of his symptoms. Autopsy showed influenzal viremia, pneumococcemia and bilateral adrenal hemorrhage. The rapid course of the patient's illness emphasizes the serious risk of sepsis for individuals who have had a splenectomy. Anti-influenza immunization in such patients should be considered."}
{"id": "PMID:8206", "title": "Malignant germ cell tumor in situ in a cryptorchid testis.", "content": "A case of a malignant undifferentiated germ cell tumor in situ of an undescended testis diagnosed by needle biopsy is described. Four similar cases have been so far recorded in the literature, all of them in the infertile men with normally descended descended testes. Two of them developed embryonal carcinoma of testis 4 1/2 later and one had a concomitant seminoma. In a high-risk group of patients (atrophic testis, cryptorchidism), a needle biopsy of a testicle may discover malignancy in its very early phase of development (Stage 0), at which time an orchiectomy alone may be a curative treatment.", "contents": "Malignant germ cell tumor in situ in a cryptorchid testis. A case of a malignant undifferentiated germ cell tumor in situ of an undescended testis diagnosed by needle biopsy is described. Four similar cases have been so far recorded in the literature, all of them in the infertile men with normally descended descended testes. Two of them developed embryonal carcinoma of testis 4 1/2 later and one had a concomitant seminoma. In a high-risk group of patients (atrophic testis, cryptorchidism), a needle biopsy of a testicle may discover malignancy in its very early phase of development (Stage 0), at which time an orchiectomy alone may be a curative treatment."}
{"id": "PMID:8207", "title": "Understanding neurotransmitters and related drugs.", "content": "Chemical neurotransmitter substances are released at the axon terminals of the central, autonomic, and peripheral nervous systems of the human body. The most well-known of the neurotransmitters are acetylcholine, norepinephrine, dopamine, and serotonin. It is these substances that facilitate the conduction of nerve impulses throughout the body, allowing the coordination of body functions and enabling response to the environment. The efective action of neurotransmitters makes the difference between health and disease states. A nurse's understanding of neurotransmitters and of many common drugs influencing their function is essential to safe nursing practice.", "contents": "Understanding neurotransmitters and related drugs. Chemical neurotransmitter substances are released at the axon terminals of the central, autonomic, and peripheral nervous systems of the human body. The most well-known of the neurotransmitters are acetylcholine, norepinephrine, dopamine, and serotonin. It is these substances that facilitate the conduction of nerve impulses throughout the body, allowing the coordination of body functions and enabling response to the environment. The efective action of neurotransmitters makes the difference between health and disease states. A nurse's understanding of neurotransmitters and of many common drugs influencing their function is essential to safe nursing practice."}
{"id": "PMID:8208", "title": "Muscular work and the release of prostaglandin-like substances.", "content": "Experimental evidence for the release of prostaglandin-like substances, mainly of the E type, into the venous outflow from working skeletal muscles in the dog is described. Muscular exercise of the hind-leg produced by sciatic nerve stimulation evoked the release of prostaglandin-like substances detected in femoral venous blood by the bioassay method. This release occurred during and after muscular work, was abolished by indomethacin, and was not present in gallamine-treated dogs. The results suggest that endogenous vasodilator prostaglandins released during and after muscular work may contribute to local hyperaemic response during and, mainly, after muscular activity.", "contents": "Muscular work and the release of prostaglandin-like substances. Experimental evidence for the release of prostaglandin-like substances, mainly of the E type, into the venous outflow from working skeletal muscles in the dog is described. Muscular exercise of the hind-leg produced by sciatic nerve stimulation evoked the release of prostaglandin-like substances detected in femoral venous blood by the bioassay method. This release occurred during and after muscular work, was abolished by indomethacin, and was not present in gallamine-treated dogs. The results suggest that endogenous vasodilator prostaglandins released during and after muscular work may contribute to local hyperaemic response during and, mainly, after muscular activity."}
{"id": "PMID:8210", "title": "Fine structure of complex ocelli of a cubomedusan, Tamoya bursaria Haeckel.", "content": "The retina of the distal and proximal lens-bearing complex ocelli are composed of pigmented sensory cells and long pigmented cells. A ciliary sheath from each sensory cell, together with the processes of long pigmented cells, extends through the vitreous layer as far as the capsule that envelops the lens. Each ciliary sheath has several ballon-like swellings and the ciliary microtubules, arranged in the 9+2 pattern in the proximal part, are markedly disorganized distally in the swollen parts, out of which extends most of the microvilli in the vitreous layer. It is suggested that some of the microvilli may originate in vesicles that are constricted off from the surface of the pigmented sensory cells. Closely packed microvilli run in parallel in short bundles. In addition to characteristic junctions between sensory cells, junctions that are presumably synaptic and, of a new type in coelenterates, are observed between sensory cells and nerve endings.", "contents": "Fine structure of complex ocelli of a cubomedusan, Tamoya bursaria Haeckel. The retina of the distal and proximal lens-bearing complex ocelli are composed of pigmented sensory cells and long pigmented cells. A ciliary sheath from each sensory cell, together with the processes of long pigmented cells, extends through the vitreous layer as far as the capsule that envelops the lens. Each ciliary sheath has several ballon-like swellings and the ciliary microtubules, arranged in the 9+2 pattern in the proximal part, are markedly disorganized distally in the swollen parts, out of which extends most of the microvilli in the vitreous layer. It is suggested that some of the microvilli may originate in vesicles that are constricted off from the surface of the pigmented sensory cells. Closely packed microvilli run in parallel in short bundles. In addition to characteristic junctions between sensory cells, junctions that are presumably synaptic and, of a new type in coelenterates, are observed between sensory cells and nerve endings."}
{"id": "PMID:8211", "title": "The mechanism of action of ppGpp on rRNA synthesis in vitro.", "content": "We have studied the mechanism of the specific inhibition of ribosomal RNA synthesis by ppGpp in a purified system using as templates E. coli DNA and DNA from lambdad5ilv, which carries a rRNA cistron from E. coli. Ribosomal RNA synthesis, as well as its inhibition by ppGpp, are critically salt-dependent. Of a number of guanosine phosphates tested, only pppGpp (MS II) mimicked the action of ppGpp, establishing the specificity of ppGpp. The two templates gave similar results for rRNA synthesis in all experiments. By using the initiation inhibitor rifampicin, we could show that the specific inhibition of rRNA synthesis by ppGpp is due to its effect on rRNA initiation. The somewhat variable inhibition of RNA synthesis in general by ppGpp is mainly or wholly a consequence of premature chain termination. We propose that ppGpp specifically inhibits rRNA synthesis by acting on the formation of the so-called \"closed-promoter complex\".", "contents": "The mechanism of action of ppGpp on rRNA synthesis in vitro. We have studied the mechanism of the specific inhibition of ribosomal RNA synthesis by ppGpp in a purified system using as templates E. coli DNA and DNA from lambdad5ilv, which carries a rRNA cistron from E. coli. Ribosomal RNA synthesis, as well as its inhibition by ppGpp, are critically salt-dependent. Of a number of guanosine phosphates tested, only pppGpp (MS II) mimicked the action of ppGpp, establishing the specificity of ppGpp. The two templates gave similar results for rRNA synthesis in all experiments. By using the initiation inhibitor rifampicin, we could show that the specific inhibition of rRNA synthesis by ppGpp is due to its effect on rRNA initiation. The somewhat variable inhibition of RNA synthesis in general by ppGpp is mainly or wholly a consequence of premature chain termination. We propose that ppGpp specifically inhibits rRNA synthesis by acting on the formation of the so-called \"closed-promoter complex\"."}
{"id": "PMID:8212", "title": "Glutamine-stimulated modification and degradation of glutamine synthetase in hepatoma tissue culture cells.", "content": "Effects of glutamine on glutamine synthetase (GS) activity of hepatoma tissue culture (HTC) cells were studied with the aid of a specific goat anti-rat GS serum. Immunodiffusion and immunoelectrophoretic tests show that rat liver GS and HTC cell GS are immunologically similar but not identical. Immunotitrations of HTC cell extracts demonstrate that in cells incubated in high concentrations (5 mM) of glutamine, a cross-reacting form of GS with a decreased enzyme-specific activity accumulates. On prolonged incubation of cells in high glutamine, there is net degradation of GS to form immunologically inactive products. Radio-immunoprecipitation experiments show that glutamine acts by accelerating the degradation of preformed GS.", "contents": "Glutamine-stimulated modification and degradation of glutamine synthetase in hepatoma tissue culture cells. Effects of glutamine on glutamine synthetase (GS) activity of hepatoma tissue culture (HTC) cells were studied with the aid of a specific goat anti-rat GS serum. Immunodiffusion and immunoelectrophoretic tests show that rat liver GS and HTC cell GS are immunologically similar but not identical. Immunotitrations of HTC cell extracts demonstrate that in cells incubated in high concentrations (5 mM) of glutamine, a cross-reacting form of GS with a decreased enzyme-specific activity accumulates. On prolonged incubation of cells in high glutamine, there is net degradation of GS to form immunologically inactive products. Radio-immunoprecipitation experiments show that glutamine acts by accelerating the degradation of preformed GS."}
{"id": "PMID:8213", "title": "Membrane receptors for murine leukemia viruses: characterization using the purified viral envelope glycoprotein, gp71.", "content": "The 71,000 dalton glycoprotein (gp71) purified from Rauscher murine leukemia virus (R-MuLV) by affinity chromatography specifically binds to murine but not other mammalian cells in culture. Binding is prevented by specific antiserum raides to gp71 (anti-gp71). The binding assay as described in this report can detect receptors on as few as 300 murine cells, and with 1 X 10(5) cells gives significant binding with 30 sec. The results show that the purified glycoprotein retians biologic activity and can form a stable complex with specific receptors on mouse cell membranes. The assay can therefore be used to characterize the nature of the cellular receptors that are essential for leukemia virus infection. Purified gp71 binding to mouse cells is prevented if the cells are actively producing related ecotropic type C viruses, presumably because the receptors are occupied and are not available to bind exogenously applied gp71. The binding of gp71 to murine cells is enhanced by the presence of calcium ions and low pH. Binding studies performed using an excess of 125I-gp71 indicate the NIH/3T3 cells bind approximately 5.3 X 10(5) molecules of 125I-gp71 per cell.", "contents": "Membrane receptors for murine leukemia viruses: characterization using the purified viral envelope glycoprotein, gp71. The 71,000 dalton glycoprotein (gp71) purified from Rauscher murine leukemia virus (R-MuLV) by affinity chromatography specifically binds to murine but not other mammalian cells in culture. Binding is prevented by specific antiserum raides to gp71 (anti-gp71). The binding assay as described in this report can detect receptors on as few as 300 murine cells, and with 1 X 10(5) cells gives significant binding with 30 sec. The results show that the purified glycoprotein retians biologic activity and can form a stable complex with specific receptors on mouse cell membranes. The assay can therefore be used to characterize the nature of the cellular receptors that are essential for leukemia virus infection. Purified gp71 binding to mouse cells is prevented if the cells are actively producing related ecotropic type C viruses, presumably because the receptors are occupied and are not available to bind exogenously applied gp71. The binding of gp71 to murine cells is enhanced by the presence of calcium ions and low pH. Binding studies performed using an excess of 125I-gp71 indicate the NIH/3T3 cells bind approximately 5.3 X 10(5) molecules of 125I-gp71 per cell."}
{"id": "PMID:8214", "title": "Naturally occurring cross-links in yeast chromosomal DNA.", "content": "Chromosome-size yeast DNA molecules with a number average molecular weight (Mn) of 3-4 X 10(8) were isolated from sucrose gradients after sedimentation of lysed yeast spheroplasts. Resedimentation showed that the molecules were isolated without introducing appreciable single-strand or double-strand breaks. The presence of cross-links in these molecules was suggested by the observation that the apparent Mn in alkali was greater than expected for separated single strands. Since cross-linked molecules would have strands which fail to separate upon denaturation, this was tested more directly. Neutralization of alkaline denaturing conditions resulted in up to 70% of the intact molecules rapidly reforming duplex structures, as shown by equilibrium banding in CsCI. Experiments with larger E. coli DNA molecules (Mn = 5.2 X 10(8)) indicated that the conditions used were sufficient to denature completely molecules of this size. Results of enzyme treatments suggest that the cross-links are not RNA or protein. Experiments with density-labeled yeast DNA molecules showed that the rapid reformation of duplex DNA is not the consequence either of a bimolecular reaction between separated DNA strands or of intrastrand renaturation. The data indicate that when the yeast DNA molecules are completely denatured, the strands fail to separate. Hence they must be cross-linked. Experiments with sheared DNA show that there are small number of cross-links, one to four, permolecule.", "contents": "Naturally occurring cross-links in yeast chromosomal DNA. Chromosome-size yeast DNA molecules with a number average molecular weight (Mn) of 3-4 X 10(8) were isolated from sucrose gradients after sedimentation of lysed yeast spheroplasts. Resedimentation showed that the molecules were isolated without introducing appreciable single-strand or double-strand breaks. The presence of cross-links in these molecules was suggested by the observation that the apparent Mn in alkali was greater than expected for separated single strands. Since cross-linked molecules would have strands which fail to separate upon denaturation, this was tested more directly. Neutralization of alkaline denaturing conditions resulted in up to 70% of the intact molecules rapidly reforming duplex structures, as shown by equilibrium banding in CsCI. Experiments with larger E. coli DNA molecules (Mn = 5.2 X 10(8)) indicated that the conditions used were sufficient to denature completely molecules of this size. Results of enzyme treatments suggest that the cross-links are not RNA or protein. Experiments with density-labeled yeast DNA molecules showed that the rapid reformation of duplex DNA is not the consequence either of a bimolecular reaction between separated DNA strands or of intrastrand renaturation. The data indicate that when the yeast DNA molecules are completely denatured, the strands fail to separate. Hence they must be cross-linked. Experiments with sheared DNA show that there are small number of cross-links, one to four, permolecule."}
{"id": "PMID:8216", "title": "The effect of allyl compounds on hepatic microsomal mixed function oxidation and porphyrogenesis.", "content": "The activities of 5-aminolaevulinate (5-ALA) synthetase and of various microsomat drug-metabolising enzymes have been determined in the livers of rats pretreated with different drugs and chemicals containing the allyl group. Safrole, isosafrole and secobarbital gave rise to slight increases in 5-ALA synthetase, whereas alclophenac and triallyl cyanurate almost doubled the enzyme activity and the known porphyrogenic agents, allylisopropylacetamide (AIA) and allobarbital caused increases of 1.5- and 2.5-fold, respectively. Allobarbital induced the microsomal drug-metabolising enzymes while secobarbital had only a weak effect and alclophenac and triallyl cyanurate had no effect at all. From these results it is suggested that induction of the synthesis of cytochrome P-450 is not rate dependent on the synthesis haem and induction of porphyrin biosynthesis.", "contents": "The effect of allyl compounds on hepatic microsomal mixed function oxidation and porphyrogenesis. The activities of 5-aminolaevulinate (5-ALA) synthetase and of various microsomat drug-metabolising enzymes have been determined in the livers of rats pretreated with different drugs and chemicals containing the allyl group. Safrole, isosafrole and secobarbital gave rise to slight increases in 5-ALA synthetase, whereas alclophenac and triallyl cyanurate almost doubled the enzyme activity and the known porphyrogenic agents, allylisopropylacetamide (AIA) and allobarbital caused increases of 1.5- and 2.5-fold, respectively. Allobarbital induced the microsomal drug-metabolising enzymes while secobarbital had only a weak effect and alclophenac and triallyl cyanurate had no effect at all. From these results it is suggested that induction of the synthesis of cytochrome P-450 is not rate dependent on the synthesis haem and induction of porphyrin biosynthesis."}
{"id": "PMID:8217", "title": "The action of a binary nonionic detergent on a kidney membrane fraction.", "content": "The disruption of a kidney cortex microsomal membrane preparation by a binary, nonionic detergent, was followed by using as markers, the changes in total protein content, and (Na+, K+)-ATPase in a supernatant fraction. Both markers responded similarly to changes in pH, microsome concentration and detergent concentration, but responded differently for time-dependent studies. The (Na+, K+)-ATPase activity was increased 2.2-fold (76.1 mumoles Pi/mg protein/h, 95% ouabain-sensitive) by a single detergent treatment and 3.5-fold (92% ouabain-sensitive) by a sequential detergent treatment. Changes in the critical micelle concentration (cmc) were observed for varying detergent and protein concentrations, which suggest interactions of monomeric detergent with the membrane. The peak of (Na+, K+)-ATPase activity occurred above the cmc which suggests the participation of micelles in releasing the enzyme from the membranes. Hill plots of the protein released as the detergent concentration was varied showed a change in the slope near the cmc indicating a four-fold increase in the binding of detergent to membranes as the detergent concentration is increased above the cmc. These results suggest that the disruption of membranes by detergent involves the binding of detergent monomers to the membrane followed by the formation of co-micelles of the detergent with segments of the membrane to complete the separation process.", "contents": "The action of a binary nonionic detergent on a kidney membrane fraction. The disruption of a kidney cortex microsomal membrane preparation by a binary, nonionic detergent, was followed by using as markers, the changes in total protein content, and (Na+, K+)-ATPase in a supernatant fraction. Both markers responded similarly to changes in pH, microsome concentration and detergent concentration, but responded differently for time-dependent studies. The (Na+, K+)-ATPase activity was increased 2.2-fold (76.1 mumoles Pi/mg protein/h, 95% ouabain-sensitive) by a single detergent treatment and 3.5-fold (92% ouabain-sensitive) by a sequential detergent treatment. Changes in the critical micelle concentration (cmc) were observed for varying detergent and protein concentrations, which suggest interactions of monomeric detergent with the membrane. The peak of (Na+, K+)-ATPase activity occurred above the cmc which suggests the participation of micelles in releasing the enzyme from the membranes. Hill plots of the protein released as the detergent concentration was varied showed a change in the slope near the cmc indicating a four-fold increase in the binding of detergent to membranes as the detergent concentration is increased above the cmc. These results suggest that the disruption of membranes by detergent involves the binding of detergent monomers to the membrane followed by the formation of co-micelles of the detergent with segments of the membrane to complete the separation process."}
{"id": "PMID:8218", "title": "Resistance of alkylated DNA to degradation by deoxyribonuclease II at neutral and acid pH.", "content": "Methylation of a calf thymus DNA substrate by dimethyl sulphate (DMS) leads to an inhibition of deoxyribonuclease II activity which is gradually lost with time. The extent of this initial inhibition is linearly related to the amount of methylated products in DNA and quantitatively similar effects were found when the enzyme was used under either acid or neutral conditions. Deoxyribonuclease II was shown to produce 3'-phosphate termini under both acid and neutral conditions and thus, irrespective of the ionic conditions for the action of this enzyme in vivo the effects demonstrated here are of potential significance. Local denaturation of the methylated DNA may be partly responsible for these inhibitory effects but it is likely that the methyl purines also play a more direct role.", "contents": "Resistance of alkylated DNA to degradation by deoxyribonuclease II at neutral and acid pH. Methylation of a calf thymus DNA substrate by dimethyl sulphate (DMS) leads to an inhibition of deoxyribonuclease II activity which is gradually lost with time. The extent of this initial inhibition is linearly related to the amount of methylated products in DNA and quantitatively similar effects were found when the enzyme was used under either acid or neutral conditions. Deoxyribonuclease II was shown to produce 3'-phosphate termini under both acid and neutral conditions and thus, irrespective of the ionic conditions for the action of this enzyme in vivo the effects demonstrated here are of potential significance. Local denaturation of the methylated DNA may be partly responsible for these inhibitory effects but it is likely that the methyl purines also play a more direct role."}
{"id": "PMID:8219", "title": "Enzymatic properties of native and N-ethylmaleimide-modified cardiac myosin from normal and thyrotoxic rabbits.", "content": "Cardiac myosin from thyrotoxic animals (myosin-T) exhibits elevated Ca2+ -ATPase activity which is resistant to further stimulation by sulfhydryl modification. In the present study, we have compared the enzymatic properties of myosin-T with those of myosin from euthyroid rabbits (myosin-N) and the derivatives of myosin-T and myosin-N formed by blocking the most rapidly reacting class of thiols (SH1) with N-ethylmaleimide (NEM). Vmax for Ca2+ -ATPase of myosin-T was about 250% greater than myosin-N and was nearly the same as NEM-modified myosin-N. Values for the apparent Km of myosin-T and NEM-modified myosin-N were 200% greater than the value for unmodified myosin-N. Vmax and Km for K+ (EDTA)-ATPase activity of NEM-modified myosin-T and myosin-N were identical. The Ca2+ saturation, pH, and salt-dependency curves for the ATPase activity of myosin-T were parallel to the curves for myosin-N and differed from those for the NEM-modified myosins. Myosin-T exhibited an increased rate of hydrolysis of ATP, CTP, and UTP in both low (0.05m) and high (0.5m) KCl medium. NEM-modified myosin-N showed increased hydrolysis of ATP and CTP in low KCl medium and increased hydrolysis of ATP, CTP, and UTP in high KCl medium. These results support the hypothesis that the enzymatic behavior of myosin-T may be caused by an alteration in the active site near the SH, thiols. The unique enzymatic properties of myosin-T did not seem to be the result of a major change in structure. The electrophoretic pattern of light chains from myosin-T and myosin-N was the same in polyacrylamide gels containing either 8 M urea at pH 8.6 or sodium dodecyl sulfate. Also, myosin-T had a normal amino acid composition and lacked 3-methyl-histidine and hot acid-stable phosphate.", "contents": "Enzymatic properties of native and N-ethylmaleimide-modified cardiac myosin from normal and thyrotoxic rabbits. Cardiac myosin from thyrotoxic animals (myosin-T) exhibits elevated Ca2+ -ATPase activity which is resistant to further stimulation by sulfhydryl modification. In the present study, we have compared the enzymatic properties of myosin-T with those of myosin from euthyroid rabbits (myosin-N) and the derivatives of myosin-T and myosin-N formed by blocking the most rapidly reacting class of thiols (SH1) with N-ethylmaleimide (NEM). Vmax for Ca2+ -ATPase of myosin-T was about 250% greater than myosin-N and was nearly the same as NEM-modified myosin-N. Values for the apparent Km of myosin-T and NEM-modified myosin-N were 200% greater than the value for unmodified myosin-N. Vmax and Km for K+ (EDTA)-ATPase activity of NEM-modified myosin-T and myosin-N were identical. The Ca2+ saturation, pH, and salt-dependency curves for the ATPase activity of myosin-T were parallel to the curves for myosin-N and differed from those for the NEM-modified myosins. Myosin-T exhibited an increased rate of hydrolysis of ATP, CTP, and UTP in both low (0.05m) and high (0.5m) KCl medium. NEM-modified myosin-N showed increased hydrolysis of ATP and CTP in low KCl medium and increased hydrolysis of ATP, CTP, and UTP in high KCl medium. These results support the hypothesis that the enzymatic behavior of myosin-T may be caused by an alteration in the active site near the SH, thiols. The unique enzymatic properties of myosin-T did not seem to be the result of a major change in structure. The electrophoretic pattern of light chains from myosin-T and myosin-N was the same in polyacrylamide gels containing either 8 M urea at pH 8.6 or sodium dodecyl sulfate. Also, myosin-T had a normal amino acid composition and lacked 3-methyl-histidine and hot acid-stable phosphate."}
{"id": "PMID:8220", "title": "The association between serum triglycerides and gamma glutamyl transpeptidase activity in diabetes mellitus.", "content": "A study conducted on 228 diabetic patients has shown a significant positive association between serum gamma-glutamyl transpeptidase (GGT) and triglyceride levels. Both fall with treatment, the most marked reduction occurring in patients on insulin. We suggest that the association between serum GGT and triglyceride levels and also the higher incidence of raised GGT and triglyceride levels in new diabetics may reflect hepatic microsomal enzyme induction of the rate-limiting enzymes of triglyceride synthesis. Serum GGT does not seem to correlate with hepatomegaly in diabetes mellitus.", "contents": "The association between serum triglycerides and gamma glutamyl transpeptidase activity in diabetes mellitus. A study conducted on 228 diabetic patients has shown a significant positive association between serum gamma-glutamyl transpeptidase (GGT) and triglyceride levels. Both fall with treatment, the most marked reduction occurring in patients on insulin. We suggest that the association between serum GGT and triglyceride levels and also the higher incidence of raised GGT and triglyceride levels in new diabetics may reflect hepatic microsomal enzyme induction of the rate-limiting enzymes of triglyceride synthesis. Serum GGT does not seem to correlate with hepatomegaly in diabetes mellitus."}
{"id": "PMID:8221", "title": "Reverse-phase chromatography of polar biological substances: separation of catechol compounds by high-performance liquid chromatography.", "content": "Catecholamines and their metabolites have been separated isocratically by reverse-phase chromatography with aqueous (no organic solvent admixed) eluents. Unlike ion-exchange or ion-pair chromatography, mixtures of both acidic and basic substances can be separated in a single chromatographic run, because the retention is governed by hydrophobic interactions between the nonpolar moiety of the solute molecules and the octadecyl-silica stationary phase. The relative retention values strongly depend on the pH of the eluent, which governs the degree of dissociation of ionogenic solutes. The reproducibility of the results and the stability and efficiency of the chromatographic systems make this approach particularly attractive for use in clinical analysis.", "contents": "Reverse-phase chromatography of polar biological substances: separation of catechol compounds by high-performance liquid chromatography. Catecholamines and their metabolites have been separated isocratically by reverse-phase chromatography with aqueous (no organic solvent admixed) eluents. Unlike ion-exchange or ion-pair chromatography, mixtures of both acidic and basic substances can be separated in a single chromatographic run, because the retention is governed by hydrophobic interactions between the nonpolar moiety of the solute molecules and the octadecyl-silica stationary phase. The relative retention values strongly depend on the pH of the eluent, which governs the degree of dissociation of ionogenic solutes. The reproducibility of the results and the stability and efficiency of the chromatographic systems make this approach particularly attractive for use in clinical analysis."}
{"id": "PMID:8222", "title": "Diagnosis of infectious hepatitis by multicomponent analysis with use of field ionization mass spectrometry.", "content": "Field ionization mass spectrometry has been applied to multicomponent analysis of metabolites in human urine for the diagnosis of metabolic disorders, exemplified here by infectious hepatitis. The molecular weight profiles of carboxylic acids and of \"neutral\" metabolites in the urine of patients with infectious hepatitis were compared with those in urine of normals. The \"neutral\" metabolites showed 24 characteristic spectral differences in the range 68 to 215 atomic mass units, which provided correct diagnoses in 100% of the cases and a \"diagnostic power\" of unity. These results are even more encouraging than those obtained earlier with the acidic metabolites, where 11 mass numbers were found in the same mass range to be useful for correct diagnoses in 91% of the cases. The measurements were performed on urine samples preextracted on Amberlite XAD-2 columns. We used a quadrupole mass spectrometer interfaced with a multichannel analyzer for mass analyses.", "contents": "Diagnosis of infectious hepatitis by multicomponent analysis with use of field ionization mass spectrometry. Field ionization mass spectrometry has been applied to multicomponent analysis of metabolites in human urine for the diagnosis of metabolic disorders, exemplified here by infectious hepatitis. The molecular weight profiles of carboxylic acids and of \"neutral\" metabolites in the urine of patients with infectious hepatitis were compared with those in urine of normals. The \"neutral\" metabolites showed 24 characteristic spectral differences in the range 68 to 215 atomic mass units, which provided correct diagnoses in 100% of the cases and a \"diagnostic power\" of unity. These results are even more encouraging than those obtained earlier with the acidic metabolites, where 11 mass numbers were found in the same mass range to be useful for correct diagnoses in 91% of the cases. The measurements were performed on urine samples preextracted on Amberlite XAD-2 columns. We used a quadrupole mass spectrometer interfaced with a multichannel analyzer for mass analyses."}
{"id": "PMID:8223", "title": "Reversed-phase liquid-chromatographic analysis of hemodialysate from uremic patients.", "content": "With reversed-phase high-performance liquid chromatography we effected rapid and efficient separation of metabolites present in hemodialysate fluid from uremic patients on the artificial kidney. With an aqueous sodium acetate/methanol gradient as mobile phase, more than 50 ultraviolet-absorbing constituents were resolved in a 70-min chromatogram of a 100-mul sample of dialysate. Many of the metabolites could be detected in concentrations below 0.1 mg/liter. From results of ultraviolet spectrophotometric analysis and the gas- and liquid-chromatographic properties of standards, half the observed chromatographic peaks have been characterized or identified. The method has been shown to be more than 10-fold faster than comparable separations by ion-exchange techniques.", "contents": "Reversed-phase liquid-chromatographic analysis of hemodialysate from uremic patients. With reversed-phase high-performance liquid chromatography we effected rapid and efficient separation of metabolites present in hemodialysate fluid from uremic patients on the artificial kidney. With an aqueous sodium acetate/methanol gradient as mobile phase, more than 50 ultraviolet-absorbing constituents were resolved in a 70-min chromatogram of a 100-mul sample of dialysate. Many of the metabolites could be detected in concentrations below 0.1 mg/liter. From results of ultraviolet spectrophotometric analysis and the gas- and liquid-chromatographic properties of standards, half the observed chromatographic peaks have been characterized or identified. The method has been shown to be more than 10-fold faster than comparable separations by ion-exchange techniques."}
{"id": "PMID:8226", "title": "Human leukocyte acid hydrolases: characterization of eleven lysosomal enzymes and study of reaction conditions for their automated analysis.", "content": "The optimal reaction conditions and kinetic properties of eleven leukocyte acid hydrolases determined with the use of fluorigenic derivatives of 4-methyl-umbelliferone are described. The enzymes studied were acid phosphatase, aryl sulfatase, alpha- and beta-glucosidase, alpha- and beta-galactosidase, alpha-mannosidase, N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucuronidase and alpha-fucosidase. More than 90% of the activity of each enzyme was released into a 27,000 X g supernatant by a double sonication procedure employing 0.9% sodium chloride and 0.1% Triton X-100. The Km values obtained were similar to those previously reported for chromogenic subtrates. A single Km value could not be derived for beta-galactosidase because its double reciprocal plot was not linear. All enzymes could be measured with less than 10 mug of protein within 15 min. Activators and inhibitors studied included the chloride salts of Na+, K+, Zn2+, Ca2+, Mg2+, Hg2+, and Fe2+ as well as p-chloromercuriphenysulfonate, glutathione, BAL, EDTA, EGTA, Triton X-100 and sodium taurocholate. The reaction conditions described in this report can be used for the diagnosis of various lysosomal storage diseases and should facilitate the development of automated procedures for the analysis of these eleven enzyme activities with small quantities of blood.", "contents": "Human leukocyte acid hydrolases: characterization of eleven lysosomal enzymes and study of reaction conditions for their automated analysis. The optimal reaction conditions and kinetic properties of eleven leukocyte acid hydrolases determined with the use of fluorigenic derivatives of 4-methyl-umbelliferone are described. The enzymes studied were acid phosphatase, aryl sulfatase, alpha- and beta-glucosidase, alpha- and beta-galactosidase, alpha-mannosidase, N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucuronidase and alpha-fucosidase. More than 90% of the activity of each enzyme was released into a 27,000 X g supernatant by a double sonication procedure employing 0.9% sodium chloride and 0.1% Triton X-100. The Km values obtained were similar to those previously reported for chromogenic subtrates. A single Km value could not be derived for beta-galactosidase because its double reciprocal plot was not linear. All enzymes could be measured with less than 10 mug of protein within 15 min. Activators and inhibitors studied included the chloride salts of Na+, K+, Zn2+, Ca2+, Mg2+, Hg2+, and Fe2+ as well as p-chloromercuriphenysulfonate, glutathione, BAL, EDTA, EGTA, Triton X-100 and sodium taurocholate. The reaction conditions described in this report can be used for the diagnosis of various lysosomal storage diseases and should facilitate the development of automated procedures for the analysis of these eleven enzyme activities with small quantities of blood."}
{"id": "PMID:8227", "title": "Oestrogen induced hypertriglyceridaemia: role of the adrenal cortex.", "content": "The role of the adrenal cortex in the pathogenesis of hypertriglyceridaemia associated with the intake of oral contraceptive agents containing oestrogen has been investigated in rats. Bilateral adrenalectomy reduced the activity of hepatic enzymes regulating lipogenesis (acetyl CoA carboxylase, fatty acid synthetase) and decreased plasma triglyceride concentrations. On the other hand, the administration of high dosage corticosterone induced the activity of hepatic enzymes with consequent elevation in serum triglyceride levels. In animals with intact adrenals the administration of oestradiol: (a) raised plasma triglyceride levels, (b) enhanced the activity of hepatic enzymes, and (c) increased the adrenal cortex:body weight ratio. The effects (a) and (b) were not observed when both adrenals were removed prior to oestrogen therapy. High dosage corticosterone replacement was found to be essential for the oestradiol to produce its effects on hepatic enzymes and plasma triglyceride levels. The results suggest a regulatory role for the adrenal cortex in the homeostasis of plasma triglyceride concentration and that the hypertriglyceridaemia induced by the oestrogen containing preparations might be secondary to alterations in adrenocortical function.", "contents": "Oestrogen induced hypertriglyceridaemia: role of the adrenal cortex. The role of the adrenal cortex in the pathogenesis of hypertriglyceridaemia associated with the intake of oral contraceptive agents containing oestrogen has been investigated in rats. Bilateral adrenalectomy reduced the activity of hepatic enzymes regulating lipogenesis (acetyl CoA carboxylase, fatty acid synthetase) and decreased plasma triglyceride concentrations. On the other hand, the administration of high dosage corticosterone induced the activity of hepatic enzymes with consequent elevation in serum triglyceride levels. In animals with intact adrenals the administration of oestradiol: (a) raised plasma triglyceride levels, (b) enhanced the activity of hepatic enzymes, and (c) increased the adrenal cortex:body weight ratio. The effects (a) and (b) were not observed when both adrenals were removed prior to oestrogen therapy. High dosage corticosterone replacement was found to be essential for the oestradiol to produce its effects on hepatic enzymes and plasma triglyceride levels. The results suggest a regulatory role for the adrenal cortex in the homeostasis of plasma triglyceride concentration and that the hypertriglyceridaemia induced by the oestrogen containing preparations might be secondary to alterations in adrenocortical function."}
{"id": "PMID:8228", "title": "Increased survival times of New Zealand hybrid mice immunosuppressed by graft-versus-host reactions.", "content": "New Zealand mice develop autoimmune disease usually accompanied by glomerulonephritis. A graft-versus-host reaction was induced in New Zealand Black X New Zealand White F1 hybrid mice by administration of New Zealand White spleen cells. The mice so treated had diminished antibody responses to both an exogenous antigen (sheep red blood cells) and an endogenous antigen (native DNA).  They had much less glomerulonephritis and increased survival times compared to unmanipulated controls, apparently due to immunosuppression. Similar hybrid mice treated with high doses of cyclophosphamide (70mg/kg/week) were more immunosuppressed than mice with graft-versus-host reactions and had even greater survival times.", "contents": "Increased survival times of New Zealand hybrid mice immunosuppressed by graft-versus-host reactions. New Zealand mice develop autoimmune disease usually accompanied by glomerulonephritis. A graft-versus-host reaction was induced in New Zealand Black X New Zealand White F1 hybrid mice by administration of New Zealand White spleen cells. The mice so treated had diminished antibody responses to both an exogenous antigen (sheep red blood cells) and an endogenous antigen (native DNA).  They had much less glomerulonephritis and increased survival times compared to unmanipulated controls, apparently due to immunosuppression. Similar hybrid mice treated with high doses of cyclophosphamide (70mg/kg/week) were more immunosuppressed than mice with graft-versus-host reactions and had even greater survival times."}
{"id": "PMID:8230", "title": "Organic acidemias.", "content": "Inherited organic acidemias are a group of metabolic disorders currently being described and investigated as gas-liquid chromatography is applied to unexplained diseases of infancy and childhood. Common clinical presentations include attacks of ketoacidosis, unexplained metabolic acidosis, failure of normal development, seizures, and other neurologic abnormalities. Hyperglycinemia, hyperammonemia, and hypoglycemia are other laboratory findings frequently present. Diagnosis depends on examination of urine, and sometimes blood, by gas-liquid chromatography to measure concentrations of organic acids and organic acid derivatives. Prognosis in many cases is excellent if diagnosis is made promptly and the metabolic acidosis can be reversed. Recovery from neurologic deficits has frequently been seen. Long-term therapy is generally dependent on restricting precursors of the toxic organic acid which builds up as a consequence of the enzyme deficiency. If there is some enzyme activity retained or if alternate metabolic pathways exist, success with therapy is likely.", "contents": "Organic acidemias. Inherited organic acidemias are a group of metabolic disorders currently being described and investigated as gas-liquid chromatography is applied to unexplained diseases of infancy and childhood. Common clinical presentations include attacks of ketoacidosis, unexplained metabolic acidosis, failure of normal development, seizures, and other neurologic abnormalities. Hyperglycinemia, hyperammonemia, and hypoglycemia are other laboratory findings frequently present. Diagnosis depends on examination of urine, and sometimes blood, by gas-liquid chromatography to measure concentrations of organic acids and organic acid derivatives. Prognosis in many cases is excellent if diagnosis is made promptly and the metabolic acidosis can be reversed. Recovery from neurologic deficits has frequently been seen. Long-term therapy is generally dependent on restricting precursors of the toxic organic acid which builds up as a consequence of the enzyme deficiency. If there is some enzyme activity retained or if alternate metabolic pathways exist, success with therapy is likely."}
{"id": "PMID:8231", "title": "Antihypertensive action of propranolol in man: lack of evidence for a neural depressive effect.", "content": "The hypothesis that a neural depressive action is related to the antihypertensive effects of beta blockers has been evaluated in 14 essential hypertensive male patients through the circulatory response to noxious stimuli. The pressor reaction to mental arithmetic was primarily mediated by cardiac stimulation (beta receptors activation), that to cold by vasoconstriction (alpha receptors activation). Arithmetic and cold were tested to separate the effects of peripheral beta blackade from possible neural and other influences. After propanolol (320 mg per day for 3 wk): (1) The baseline pressure was reduced; (2) appearance, peak, and disappearance time of the circulatory reaction to either stimulus was not altered; (3) the pressor effect of arithmetic was decreased in an extent proportional to the reduced rise of cardiac output; and (4) pressure during cold reached the pretreatment levels through an augmented increase of vascular resistance. Our findings indicate that propranolol depresses only the circulatory reactions mediated through beta receptors activation and provide no evidence of effects other than beta blockade.", "contents": "Antihypertensive action of propranolol in man: lack of evidence for a neural depressive effect. The hypothesis that a neural depressive action is related to the antihypertensive effects of beta blockers has been evaluated in 14 essential hypertensive male patients through the circulatory response to noxious stimuli. The pressor reaction to mental arithmetic was primarily mediated by cardiac stimulation (beta receptors activation), that to cold by vasoconstriction (alpha receptors activation). Arithmetic and cold were tested to separate the effects of peripheral beta blackade from possible neural and other influences. After propanolol (320 mg per day for 3 wk): (1) The baseline pressure was reduced; (2) appearance, peak, and disappearance time of the circulatory reaction to either stimulus was not altered; (3) the pressor effect of arithmetic was decreased in an extent proportional to the reduced rise of cardiac output; and (4) pressure during cold reached the pretreatment levels through an augmented increase of vascular resistance. Our findings indicate that propranolol depresses only the circulatory reactions mediated through beta receptors activation and provide no evidence of effects other than beta blockade."}
{"id": "PMID:8229", "title": "Calcificaiton of growth plate cartilage with special reference to studies on micropuncture fluids.", "content": "No final comprehensive hypothesis of the chain of events involved in inhibition of calcification can be constructed at the present time. The flow diagram in Figure 1 is presented only as a working hypothesis currently used by the authors. Insofar as the Cfl is representative of native factors at calcifying sites, none of the major theories on the nature of mineral formation at present seem excluded. As in the fields of clotting and complement pathways, where backup systems seem to operate, one should not be surprised if more than one system operates in cartilaginous calcification.", "contents": "Calcificaiton of growth plate cartilage with special reference to studies on micropuncture fluids. No final comprehensive hypothesis of the chain of events involved in inhibition of calcification can be constructed at the present time. The flow diagram in Figure 1 is presented only as a working hypothesis currently used by the authors. Insofar as the Cfl is representative of native factors at calcifying sites, none of the major theories on the nature of mineral formation at present seem excluded. As in the fields of clotting and complement pathways, where backup systems seem to operate, one should not be surprised if more than one system operates in cartilaginous calcification."}
{"id": "PMID:8232", "title": "Clinical pharmacokinetics of lorazepam. I. Absorption and disposition of oral 14C-lorazepam.", "content": "Eight healthy male subjects received single 2-mg oral doses of lorazepam containing 24 muCi/mg of 2-14C-lorazepam. Multiple venous blood samples were drawn during the first 96 hr after the dose, and all urine and stool were collected for 120 hr after dosing. Concentrations of lorazepam and its metabolites in body fluids were determined by appropriate analytic techniques. Following a lag time, lorazepam was absorbed with an apparent first-order half-life of 15 min. The peak plasma concentration was 16.9 ng/ml, measured in the pooled sample drawn 2 hr after the dose, This corresponded to the time at which clinical effects appeared to be maximal. The apparent elimination half-life of lorazepam was about 12 hr. Biotransformation to a pharmacologically inactive glucuronide metabolite appeared to be the major mechanism of lorazepam clearance. A mean of 88% of administered radioactivity was recovered in urine, and 7% was recovered in stool. Lorazepam glucuronide comprised 86% of urinary reactivity; its renal clearance was 37 ml/min. Other identified metabolites included hydroxylorazepam, a quinazolinone derivative, and a quinazoline carboxylic acid; all of these were quantitatively minor.", "contents": "Clinical pharmacokinetics of lorazepam. I. Absorption and disposition of oral 14C-lorazepam. Eight healthy male subjects received single 2-mg oral doses of lorazepam containing 24 muCi/mg of 2-14C-lorazepam. Multiple venous blood samples were drawn during the first 96 hr after the dose, and all urine and stool were collected for 120 hr after dosing. Concentrations of lorazepam and its metabolites in body fluids were determined by appropriate analytic techniques. Following a lag time, lorazepam was absorbed with an apparent first-order half-life of 15 min. The peak plasma concentration was 16.9 ng/ml, measured in the pooled sample drawn 2 hr after the dose, This corresponded to the time at which clinical effects appeared to be maximal. The apparent elimination half-life of lorazepam was about 12 hr. Biotransformation to a pharmacologically inactive glucuronide metabolite appeared to be the major mechanism of lorazepam clearance. A mean of 88% of administered radioactivity was recovered in urine, and 7% was recovered in stool. Lorazepam glucuronide comprised 86% of urinary reactivity; its renal clearance was 37 ml/min. Other identified metabolites included hydroxylorazepam, a quinazolinone derivative, and a quinazoline carboxylic acid; all of these were quantitatively minor."}
{"id": "PMID:8233", "title": "Effect of age on oxygen-binding in normal human subjects.", "content": "1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years. 2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7-40 and PCO2 5-33 kPa showed a positive correlation with age. 3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7-20. On average P50 at intra-erythrocytic pH 7-20 increased from 3-59 kPa at 20 years to 3-96 kPa at 90 years of age. 4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age.", "contents": "Effect of age on oxygen-binding in normal human subjects. 1. Oxygen-binding, plasma and intra-erythrocytic pH, and haemoglobin, 2,3-diphosphoglycerate and inorganic phosphate concentrations were measured in sixty-two healthy non-smokers aged between 18 and 89 years. 2. P50 (oxygen tension at 50% oxygen saturation) expressed at plasma pH 7-40 and PCO2 5-33 kPa showed a positive correlation with age. 3. This correlation of P50 with age was closer when P50 was expressed at a constant intra-erythrocytic pH 7-20. On average P50 at intra-erythrocytic pH 7-20 increased from 3-59 kPa at 20 years to 3-96 kPa at 90 years of age. 4. 2,3-Diphosphoglycerate, inorganic phosphate, haemoglobin and mean corpuscular haemoglobin concentrations did not correlate with P50 or with age."}
{"id": "PMID:8234", "title": "Intracellular acid-base heterogeneity in nucleated avian erythrocytes.", "content": "1. Intracellular hydrogen ion activity, [H+]i, was extimated in human erythrocytes and in nucleated avian erythrocytes from measurements of the distribution of ammonia and 5,5'-dimethyloxazolidine-2,4'-dione (DMO) between intracellular and extracellular fluid. 2. In human erythrocytes there was no difference between values for [H+]i derived from measurements of either DMO or ammonia. 3. In avian erythrocytes, [H+]i(ammonia) was consistently greater than [H+]i(DMO), indicating significant acid-base heterogeneity of the intracellular water. The degree of heterogeneity was assessed by reference to a theoretical model of two compartments of equal size. 4. Experiments with nuclei isolated from avian erythrocytes suggested that DMO is not bound to nucleoproteins, and that the nucleus may be more acidic than the cytoplasm.", "contents": "Intracellular acid-base heterogeneity in nucleated avian erythrocytes. 1. Intracellular hydrogen ion activity, [H+]i, was extimated in human erythrocytes and in nucleated avian erythrocytes from measurements of the distribution of ammonia and 5,5'-dimethyloxazolidine-2,4'-dione (DMO) between intracellular and extracellular fluid. 2. In human erythrocytes there was no difference between values for [H+]i derived from measurements of either DMO or ammonia. 3. In avian erythrocytes, [H+]i(ammonia) was consistently greater than [H+]i(DMO), indicating significant acid-base heterogeneity of the intracellular water. The degree of heterogeneity was assessed by reference to a theoretical model of two compartments of equal size. 4. Experiments with nuclei isolated from avian erythrocytes suggested that DMO is not bound to nucleoproteins, and that the nucleus may be more acidic than the cytoplasm."}
{"id": "PMID:8236", "title": "Telephone management of poisonings using syrup of ipecac.", "content": "Seven hundred and seventy-six cases were studied during a six-month period to see if induction of emesis could be successfully managed at home by telephone. Emesis was successful in 98.8% of cases. In 6.7% of all cases, symptoms were found at 4-hour follow-up that were referrable to the ingestion, but all were considered to be of minor consequence. No complications of vomiting occurred. Twenty-four hour follow-up investigation indicated no significant complications of induction of emesis or complications from managing the patient by telephone. It is our conclusion that, with appropriate telephone supervision, home-induced emesis of ingestions expected to produce mild to moderate symptoms is as effective as emergency room or physician office management of cases. Furthermore, the absence of adverse affects of complications arising from the induction of emesis at home in our cases confirms that this form of management is quite safe.", "contents": "Telephone management of poisonings using syrup of ipecac. Seven hundred and seventy-six cases were studied during a six-month period to see if induction of emesis could be successfully managed at home by telephone. Emesis was successful in 98.8% of cases. In 6.7% of all cases, symptoms were found at 4-hour follow-up that were referrable to the ingestion, but all were considered to be of minor consequence. No complications of vomiting occurred. Twenty-four hour follow-up investigation indicated no significant complications of induction of emesis or complications from managing the patient by telephone. It is our conclusion that, with appropriate telephone supervision, home-induced emesis of ingestions expected to produce mild to moderate symptoms is as effective as emergency room or physician office management of cases. Furthermore, the absence of adverse affects of complications arising from the induction of emesis at home in our cases confirms that this form of management is quite safe."}
{"id": "PMID:8278", "title": "Cyclic AMP and cyclic GMP in epidermal physiology and pathophysiology.", "content": "The second messengers cyclic AMP and cyclic GMP in several organs appear to coordinate those molecular events which are responsible for specialized organ function. As a result of balanced cell proliferation and specialization, epidermis functions by terminal specialization which provides a barrier between man and environment. Since the epidermal component of psoriasis is a classic example of deranged epidermal homeostasis, which has a low level of cyclic AMP and a high level of cyclic GMP, it seems reasonable that rebalancing these cyclic nucleotides might ultimately be a safe and effective therapy for psoriasis and other proliferative skin diseases.", "contents": "Cyclic AMP and cyclic GMP in epidermal physiology and pathophysiology. The second messengers cyclic AMP and cyclic GMP in several organs appear to coordinate those molecular events which are responsible for specialized organ function. As a result of balanced cell proliferation and specialization, epidermis functions by terminal specialization which provides a barrier between man and environment. Since the epidermal component of psoriasis is a classic example of deranged epidermal homeostasis, which has a low level of cyclic AMP and a high level of cyclic GMP, it seems reasonable that rebalancing these cyclic nucleotides might ultimately be a safe and effective therapy for psoriasis and other proliferative skin diseases."}
{"id": "PMID:8283", "title": "Pleural fluid pH in parapneumonic effusions.", "content": "The pH and carbon dioxide tension were measured in 24 consecutive parapneumonic effusions, along with the leukocyte count, leukocytic differential count, and levels of glucose and protein. Three categories of parapneumonic effusions were characterized: (1) empyemas; (2) benign (nonloculated) effusions; and (3) loculated effusions. A pH greater than 7.30 was present in all ten benign effusions, and spontaneous resolution occurred in each case. All ten empyemas and the four loculated effusions had a pH less than 7.30. All four loculated effusions required drainage with a chest tube for resolution. The pH of the pleural fluid alone separated the empyemas and loculated effusions from benign effusions. The early separation of parapneumonic effusions on the basis of the pleural fluid appears useful. If the pH is greater than 7.30, a benign effusion is present, and spontaneous resolution is likely. If the pH is less than 7.30, loculation of the pleural space may occur regardless of whether the effusion fulfills the criteria for empyema.", "contents": "Pleural fluid pH in parapneumonic effusions. The pH and carbon dioxide tension were measured in 24 consecutive parapneumonic effusions, along with the leukocyte count, leukocytic differential count, and levels of glucose and protein. Three categories of parapneumonic effusions were characterized: (1) empyemas; (2) benign (nonloculated) effusions; and (3) loculated effusions. A pH greater than 7.30 was present in all ten benign effusions, and spontaneous resolution occurred in each case. All ten empyemas and the four loculated effusions had a pH less than 7.30. All four loculated effusions required drainage with a chest tube for resolution. The pH of the pleural fluid alone separated the empyemas and loculated effusions from benign effusions. The early separation of parapneumonic effusions on the basis of the pleural fluid appears useful. If the pH is greater than 7.30, a benign effusion is present, and spontaneous resolution is likely. If the pH is less than 7.30, loculation of the pleural space may occur regardless of whether the effusion fulfills the criteria for empyema."}
{"id": "PMID:8284", "title": "Lipid binding of a halothane metabolite. Relationship to lipid peroxidation in vitro.", "content": "Incubation of rat liver microsomes with 14C-halothane in a nitrogen atmosphere results in a high correlation between the formation of conjugated dienes and the binding of a halothane metabolite to phospholipids. Both the binding and the formation of the conjugated dienes required NADPH, were inhibited by carbon monoxide, and increased with duration of incubation and with protein concentration. Both [36Cl] halothane and [14C] halothane showed a similar pattern of binding to microsomal phospholipids suggesting that the chlorine atom is retained by the metabolite that binds. Neither high levels of conjugated dienes produced by halothane in microsomes incubated under nitrogen nor the binding of the halothane metabolite results in the destruction of cytochrome P-450.", "contents": "Lipid binding of a halothane metabolite. Relationship to lipid peroxidation in vitro. Incubation of rat liver microsomes with 14C-halothane in a nitrogen atmosphere results in a high correlation between the formation of conjugated dienes and the binding of a halothane metabolite to phospholipids. Both the binding and the formation of the conjugated dienes required NADPH, were inhibited by carbon monoxide, and increased with duration of incubation and with protein concentration. Both [36Cl] halothane and [14C] halothane showed a similar pattern of binding to microsomal phospholipids suggesting that the chlorine atom is retained by the metabolite that binds. Neither high levels of conjugated dienes produced by halothane in microsomes incubated under nitrogen nor the binding of the halothane metabolite results in the destruction of cytochrome P-450."}
{"id": "PMID:8285", "title": "Studies on the mechanism of toxicity and of development of tolerance to the pulmonary toxin, alpha-naphthylthiourea (ANTU).", "content": "The in vivo administration of the radiolabeled lung toxin alpha-naphthylthiourea (ANTU) to rats leads to the covalent binding of radioactivity to the macromolecules of the lung and liver. In contrast, very little radioactivity is bound in these organs when an equal amount of the 14C-labeled oxygen analog of ANTU, 14C-alpha-naphthylurea (ANU), is administered. In addition, ANU is essentially nontoxic to rats. ANTU is metabolized in vitro by lung and liver microsomes to an intermediate which covalently binds to the macromolecules of the microsomes. This covalent binding, which requires NADPH, leads to a decrease in mixed-function oxidase activity and to a decrease in the level of cytochrome P-450 detectable as its carbon monoxide complex. Incubation of microsomes with ANTU in the absence of NADPH or with ANU in the presence of NADPH, has no effect on these parameters. Pretreatment of rats with small nonlethal doses of ANTU daily for 5 days brings about a decrease in the activity of the mixed-function oxidase enzyme system in the lung which metabolizes parathion. In addition, this pretreatment decreases the toxicity of ANTU and leads to a decrease in the amount of radioactivity bound to the macromolecules of the lung when the animals are given a lethal dose of 35S-ANTU. These data suggest that the lung toxicity of ANTU is brought about by its metabolic activation and covalent binding to lung macromolecules.", "contents": "Studies on the mechanism of toxicity and of development of tolerance to the pulmonary toxin, alpha-naphthylthiourea (ANTU). The in vivo administration of the radiolabeled lung toxin alpha-naphthylthiourea (ANTU) to rats leads to the covalent binding of radioactivity to the macromolecules of the lung and liver. In contrast, very little radioactivity is bound in these organs when an equal amount of the 14C-labeled oxygen analog of ANTU, 14C-alpha-naphthylurea (ANU), is administered. In addition, ANU is essentially nontoxic to rats. ANTU is metabolized in vitro by lung and liver microsomes to an intermediate which covalently binds to the macromolecules of the microsomes. This covalent binding, which requires NADPH, leads to a decrease in mixed-function oxidase activity and to a decrease in the level of cytochrome P-450 detectable as its carbon monoxide complex. Incubation of microsomes with ANTU in the absence of NADPH or with ANU in the presence of NADPH, has no effect on these parameters. Pretreatment of rats with small nonlethal doses of ANTU daily for 5 days brings about a decrease in the activity of the mixed-function oxidase enzyme system in the lung which metabolizes parathion. In addition, this pretreatment decreases the toxicity of ANTU and leads to a decrease in the amount of radioactivity bound to the macromolecules of the lung when the animals are given a lethal dose of 35S-ANTU. These data suggest that the lung toxicity of ANTU is brought about by its metabolic activation and covalent binding to lung macromolecules."}
{"id": "PMID:8286", "title": "Stereospecific binding of timolol, a beta-adrenergic blocking agent.", "content": "The beta-adrenergic blocking agent, timolol, appears to be bound to stereospecific as well as nonspecific sites in the particulate fraction (8500g pellet) of the heart, lungs, and brain, whereas the d-isomer of timolol was bound to nonspecific sites only. Timolol disappeared from the particulate fraction at a slower rate than did its optical isomer. At 1 hr after a 0.1-mg/kg dose, the concentration of the l-form in the lung was 1.8 times that of the d-isomer and at 3 and 4 hr the difference was at least 33-fold. The concentration of 14C-timolol in the particulate fraction of rat tissues was inhibited by iv administered timolol and by the l-isomer of propanolol, but not by their corresponding d-forms. Competition for binding sites was dose dependent. Pretreatment with timolol at 0.1 and 5.0 mg/kg reduced the binding of 14C-timolol (dose, 0.1 mg/kg) to lung tissue by 41% and 86%, respectively. In the heart and lung tissue of rats, racemic timolol, propranolol, bunolol, and bunitrolol were approximately equally effective in competing for the binding sites of 14C-timolol. Practolol and sotalol and the beta 2-selective agent butoxamine did not significantly inhibit the binding of 14C-timolol. Similar competition was also observed in the whole brain of rats. This report suggests that the stereospecific binding of timolol may be related to the beta-adrenoreceptor process.", "contents": "Stereospecific binding of timolol, a beta-adrenergic blocking agent. The beta-adrenergic blocking agent, timolol, appears to be bound to stereospecific as well as nonspecific sites in the particulate fraction (8500g pellet) of the heart, lungs, and brain, whereas the d-isomer of timolol was bound to nonspecific sites only. Timolol disappeared from the particulate fraction at a slower rate than did its optical isomer. At 1 hr after a 0.1-mg/kg dose, the concentration of the l-form in the lung was 1.8 times that of the d-isomer and at 3 and 4 hr the difference was at least 33-fold. The concentration of 14C-timolol in the particulate fraction of rat tissues was inhibited by iv administered timolol and by the l-isomer of propanolol, but not by their corresponding d-forms. Competition for binding sites was dose dependent. Pretreatment with timolol at 0.1 and 5.0 mg/kg reduced the binding of 14C-timolol (dose, 0.1 mg/kg) to lung tissue by 41% and 86%, respectively. In the heart and lung tissue of rats, racemic timolol, propranolol, bunolol, and bunitrolol were approximately equally effective in competing for the binding sites of 14C-timolol. Practolol and sotalol and the beta 2-selective agent butoxamine did not significantly inhibit the binding of 14C-timolol. Similar competition was also observed in the whole brain of rats. This report suggests that the stereospecific binding of timolol may be related to the beta-adrenoreceptor process."}
{"id": "PMID:8287", "title": "Inversion of optical configuration of alpha-methylfluorene-2-acetic acid (cicloprofen) in rats and monkeys.", "content": "A simple and sensitive radiometric method to determine the individual enantiomers of cicloprofen has been developed. 14C-Cicloprofen was converted to its L-leucine diastereoisomers, which were separated by thin-layer chromatography and quantified by measuring the radioactivity in the area corresponding to each individual diastereoisomer. This technique has also been used to measure the enantiomers of unlabeled cicloprofen by condensing with 14C-labeled L-leucine. By using the radiometric method, a unique biotransformation process, the inversion of the (-)-enantiomer of alpha-methylfluorene-2-acetic acid to its (+)-enantiomer, has been demonstrated in the rat and monkey. The rate of (-)- to (+)-inversion was found to be faster in the rat than in the monkey. After single or repeated oral adminstration of the racemic modification or the (-)-enantiomer of cicloprofen to both species, the ratio of (+)- to (-)-enantiomers of cicloprofen in plasma, urine, or bile increased with time. At 5, 22, and 48 hr after oral administration of a single 50-mg/kg dose of the (-)-enantiomer, 14C-cicloprofen in rat plasma contained 20, 50, and 79%, respectively, of the (+)-enantiomer. After receiving the same dose of (-)-enantiomer, monkey plasma contained 16.5% and 32% of (+)-enantiomer at 8 and 24 hr, respectively. After oral administration of a single 50-mg/kg dose of the (+)-enantiomer of 14C-cicloprofen to rats and monkeys, the percentage of (-)-enantiomer in plasma varied from 2 to 15%. Since the administered (+)-enantiomer contained 4% of (-)-enantiomer and the (+)-enantiomer was excreted at a faster rate than its (-)-antipode by rats or monkeys, it is not known whether an occasional small percentage increase of (-)-enantiomer in plasma resulted from the (+)-to-(-) inversion, or from faster elimination of the (+)-enantiomer. Nevertheless, if (+)-to-(-) inversion does occur in these two species, the rate is much slower than for the (-)-to-(+) inversion.", "contents": "Inversion of optical configuration of alpha-methylfluorene-2-acetic acid (cicloprofen) in rats and monkeys. A simple and sensitive radiometric method to determine the individual enantiomers of cicloprofen has been developed. 14C-Cicloprofen was converted to its L-leucine diastereoisomers, which were separated by thin-layer chromatography and quantified by measuring the radioactivity in the area corresponding to each individual diastereoisomer. This technique has also been used to measure the enantiomers of unlabeled cicloprofen by condensing with 14C-labeled L-leucine. By using the radiometric method, a unique biotransformation process, the inversion of the (-)-enantiomer of alpha-methylfluorene-2-acetic acid to its (+)-enantiomer, has been demonstrated in the rat and monkey. The rate of (-)- to (+)-inversion was found to be faster in the rat than in the monkey. After single or repeated oral adminstration of the racemic modification or the (-)-enantiomer of cicloprofen to both species, the ratio of (+)- to (-)-enantiomers of cicloprofen in plasma, urine, or bile increased with time. At 5, 22, and 48 hr after oral administration of a single 50-mg/kg dose of the (-)-enantiomer, 14C-cicloprofen in rat plasma contained 20, 50, and 79%, respectively, of the (+)-enantiomer. After receiving the same dose of (-)-enantiomer, monkey plasma contained 16.5% and 32% of (+)-enantiomer at 8 and 24 hr, respectively. After oral administration of a single 50-mg/kg dose of the (+)-enantiomer of 14C-cicloprofen to rats and monkeys, the percentage of (-)-enantiomer in plasma varied from 2 to 15%. Since the administered (+)-enantiomer contained 4% of (-)-enantiomer and the (+)-enantiomer was excreted at a faster rate than its (-)-antipode by rats or monkeys, it is not known whether an occasional small percentage increase of (-)-enantiomer in plasma resulted from the (+)-to-(-) inversion, or from faster elimination of the (+)-enantiomer. Nevertheless, if (+)-to-(-) inversion does occur in these two species, the rate is much slower than for the (-)-to-(+) inversion."}
{"id": "PMID:8288", "title": "Buffer catalysis of the racemization reaction of some 5-phenylhydantoins and its relation to the in vivo metabolism of ethotoin.", "content": "Evidence is presented to show that an optical isomer of 5-phenylhydantoin is subject to racemization (interconversion) in different buffer systems. With phosphate buffers in the pH range of 6.0-7.5, it appears that the buffer-catalyzed racemization reaction is due solely to catalysis by divalent phosphate (general base catalysis). Other buffers studied include arsenate, imidazole, triethanolamine, and pyrophosphate. When 5-phenylhydantoin, the N-de-ethylated metabolite of ethotoin, was administered to dogs in an earlier investigation, the observation was made that somewhat more than the theoretical quantity (50 mole percent of the dose) of the substances recovered from urine had the R-configuration. The principal metabolite was (R)-(-)-2-phenylhydantoic acid, formed stereo-specifically in a ring-opening reaction of (R)-5-phyenylhydantoin by dihydropyrimidinase (EC 3.5.2.2). The results of the present in vitro study support the hypothesis that in vivo the interconversion of the optical isomers of 5-phenylhydantoin can be catalyzed by buffering components of the mammalian physiological system, and that the catalytic activities of the endogenous buffer components can account for the racemization and ultimate metabolism of the (S)-isomer of 5-phenylhydantoin by dihydropyrimidinase.", "contents": "Buffer catalysis of the racemization reaction of some 5-phenylhydantoins and its relation to the in vivo metabolism of ethotoin. Evidence is presented to show that an optical isomer of 5-phenylhydantoin is subject to racemization (interconversion) in different buffer systems. With phosphate buffers in the pH range of 6.0-7.5, it appears that the buffer-catalyzed racemization reaction is due solely to catalysis by divalent phosphate (general base catalysis). Other buffers studied include arsenate, imidazole, triethanolamine, and pyrophosphate. When 5-phenylhydantoin, the N-de-ethylated metabolite of ethotoin, was administered to dogs in an earlier investigation, the observation was made that somewhat more than the theoretical quantity (50 mole percent of the dose) of the substances recovered from urine had the R-configuration. The principal metabolite was (R)-(-)-2-phenylhydantoic acid, formed stereo-specifically in a ring-opening reaction of (R)-5-phyenylhydantoin by dihydropyrimidinase (EC 3.5.2.2). The results of the present in vitro study support the hypothesis that in vivo the interconversion of the optical isomers of 5-phenylhydantoin can be catalyzed by buffering components of the mammalian physiological system, and that the catalytic activities of the endogenous buffer components can account for the racemization and ultimate metabolism of the (S)-isomer of 5-phenylhydantoin by dihydropyrimidinase."}
{"id": "PMID:8289", "title": "5,5-Bis(3-hydroxyphenyl)hydantoin, a minor metabolite of diphenylhydantoin (dilantin) in the rat and human.", "content": "5,5-Bis(4-hydroxyphenyl) hydantoin has been identified as a minor metabolite of diphenylhydantoin (DPH) in the rat and human. This metabolite was synthesized in the laboratory from 4,4'-dihydroxybenzophenone. Gas chromatographic and mass spectrometric comparison of the permethylated synthetic compound with the permethylated derivative of the metabolite obtained from biological sources showed that they were identical. The metabolite was excreted as a glucuronide and accounted for about 1% of the total hydroxylated metabolites of DPH in human urine and rat bile. When the synthetic standard was added to the recirculating perfusate of the isolated perfused rat liver, a monoglucuronide, a trihydroxy-DPH glucuronide, and a dihydroxymethoxy-DPH glucuronide were identified in the bile.", "contents": "5,5-Bis(3-hydroxyphenyl)hydantoin, a minor metabolite of diphenylhydantoin (dilantin) in the rat and human. 5,5-Bis(4-hydroxyphenyl) hydantoin has been identified as a minor metabolite of diphenylhydantoin (DPH) in the rat and human. This metabolite was synthesized in the laboratory from 4,4'-dihydroxybenzophenone. Gas chromatographic and mass spectrometric comparison of the permethylated synthetic compound with the permethylated derivative of the metabolite obtained from biological sources showed that they were identical. The metabolite was excreted as a glucuronide and accounted for about 1% of the total hydroxylated metabolites of DPH in human urine and rat bile. When the synthetic standard was added to the recirculating perfusate of the isolated perfused rat liver, a monoglucuronide, a trihydroxy-DPH glucuronide, and a dihydroxymethoxy-DPH glucuronide were identified in the bile."}
{"id": "PMID:8290", "title": "Metabolism of dihalomethanes to formaldehyde and inorganic halide. I. In vitro studies.", "content": "Metabolism of dihalomethanes by rat liver cytosol fractions yielded formaldehyde and inorganic halide as products. Loss of metabolic activity resulting from dialysis of the cytosol was restored with glutathione. Cysteine could not substitute for GSH. No other cofactor was found to be required for activity. The optimum conditions for this biotransformation with respect to time, temperature, protein concentration, and pH were determined. Rates of metabolism of dihalomethanes showed the following order: CH2i2 greater than CH2Br2 congruent to CH2BrCi greater than CH2Ci2. Administration of the enzyme inducer, phenobarbital, to rats did not alter this metabolic pathway nor did repeated administration of CH2Br2 or CH2Ci2 change the rate of metabolism. The enzyme catalyzing this reaction was localized in the liver. Compounds known to serve as substrates for various GSH transferases inhibited the reaction as did those capable of interacting with sulfhydryl groups.", "contents": "Metabolism of dihalomethanes to formaldehyde and inorganic halide. I. In vitro studies. Metabolism of dihalomethanes by rat liver cytosol fractions yielded formaldehyde and inorganic halide as products. Loss of metabolic activity resulting from dialysis of the cytosol was restored with glutathione. Cysteine could not substitute for GSH. No other cofactor was found to be required for activity. The optimum conditions for this biotransformation with respect to time, temperature, protein concentration, and pH were determined. Rates of metabolism of dihalomethanes showed the following order: CH2i2 greater than CH2Br2 congruent to CH2BrCi greater than CH2Ci2. Administration of the enzyme inducer, phenobarbital, to rats did not alter this metabolic pathway nor did repeated administration of CH2Br2 or CH2Ci2 change the rate of metabolism. The enzyme catalyzing this reaction was localized in the liver. Compounds known to serve as substrates for various GSH transferases inhibited the reaction as did those capable of interacting with sulfhydryl groups."}
{"id": "PMID:8291", "title": "Metabolism of 2,4,5,2',5'-pentachlorobiphenyl in the rat. Qualitative and quantitative aspects.", "content": "The metabolism of 2,4,5,2',5'-pentachloro [14C] biphenyl (5-CB) was studied in the male rat. Following iv administration of 5-CB (0.6 mg/kg), 84% of the total dose was excreted within 7 days and 89% of the radioactivity excreted was in the form of 5-CB metabolites. Mass spectral and proton nuclear magnetic resonance analysis or chemical methods in conjunction with mass spectral analysis were used to identify the metabolites. The major metabolite was identified as 3'-hydroxy 5-CB. One minor metabolite was identified as the 3',4'-dihydrodiol of 5-CB and a second minor metabolite was tentatively identified as 3',4'-dihydroxy-5-CB. The relative amounts of 5-CB and its metabolites excreted in the urine and feces were also determined.", "contents": "Metabolism of 2,4,5,2',5'-pentachlorobiphenyl in the rat. Qualitative and quantitative aspects. The metabolism of 2,4,5,2',5'-pentachloro [14C] biphenyl (5-CB) was studied in the male rat. Following iv administration of 5-CB (0.6 mg/kg), 84% of the total dose was excreted within 7 days and 89% of the radioactivity excreted was in the form of 5-CB metabolites. Mass spectral and proton nuclear magnetic resonance analysis or chemical methods in conjunction with mass spectral analysis were used to identify the metabolites. The major metabolite was identified as 3'-hydroxy 5-CB. One minor metabolite was identified as the 3',4'-dihydrodiol of 5-CB and a second minor metabolite was tentatively identified as 3',4'-dihydroxy-5-CB. The relative amounts of 5-CB and its metabolites excreted in the urine and feces were also determined."}
{"id": "PMID:8292", "title": "3-(Hydroxymethyl)-8-methoxychromone and unconjugated metabolites in rat plasma. Identification of the biologically active species.", "content": "After administering 14C-labeled 3-(hydroxymethyl)-8-methoxychromone to rats by gavage, plasma was found to contain unchanged compound and three unconjugated metabolites. These metabolites were identified as 3-carboxy-8-methoxychromone, 8-methoxychromone, and 2-hydroxy-3-methoxyactophenone. The plasma levels of all four labeled compounds were determined from 30 min to 48 hr after drug administration. Only the levels of 3-(hydroxymethyl)-8-methoxychromone and 3-carboxy-8-methoxychromone correlated with the expression of antiallergy activity in the rat, and only these compounds were found to be active in vivo. However, a test system for the inhibition of anaphylactic histamine release in vitro showed activity only for 3-carboxy-8-methoxychromone.", "contents": "3-(Hydroxymethyl)-8-methoxychromone and unconjugated metabolites in rat plasma. Identification of the biologically active species. After administering 14C-labeled 3-(hydroxymethyl)-8-methoxychromone to rats by gavage, plasma was found to contain unchanged compound and three unconjugated metabolites. These metabolites were identified as 3-carboxy-8-methoxychromone, 8-methoxychromone, and 2-hydroxy-3-methoxyactophenone. The plasma levels of all four labeled compounds were determined from 30 min to 48 hr after drug administration. Only the levels of 3-(hydroxymethyl)-8-methoxychromone and 3-carboxy-8-methoxychromone correlated with the expression of antiallergy activity in the rat, and only these compounds were found to be active in vivo. However, a test system for the inhibition of anaphylactic histamine release in vitro showed activity only for 3-carboxy-8-methoxychromone."}
{"id": "PMID:8293", "title": "Metabolism of tripelennamine in man.", "content": "Four polar metabolites were isolated from the urine of human subjects orally treated with tripelennamine, and their structures elucidated by various chemical and physical methods. One of the metabolites, which is a minor one, was identified as an N-oxide of tripelennamine, and the other three as glucuronide conjugates. One of the conjugates, which is a major metabolite, has been assigned a unique quaternary ammonium N-glucuronide structure, since it gave tripelennamine and D-glucuronic acid on incubation with beta-glucuronidase. The N-oxide, which has also been prepared synthetically, remained unchanged on similar treatment. The other two conjugates were O-glucuronides of hydroxylated derivatives, the glucuronide of hydroxytripelennamine being the principal metabolite. No desmethyltripelennamine was found in the urine, however. Hydroxylation in both cases had occurred in the pyridine ring.", "contents": "Metabolism of tripelennamine in man. Four polar metabolites were isolated from the urine of human subjects orally treated with tripelennamine, and their structures elucidated by various chemical and physical methods. One of the metabolites, which is a minor one, was identified as an N-oxide of tripelennamine, and the other three as glucuronide conjugates. One of the conjugates, which is a major metabolite, has been assigned a unique quaternary ammonium N-glucuronide structure, since it gave tripelennamine and D-glucuronic acid on incubation with beta-glucuronidase. The N-oxide, which has also been prepared synthetically, remained unchanged on similar treatment. The other two conjugates were O-glucuronides of hydroxylated derivatives, the glucuronide of hydroxytripelennamine being the principal metabolite. No desmethyltripelennamine was found in the urine, however. Hydroxylation in both cases had occurred in the pyridine ring."}
{"id": "PMID:8294", "title": "Disposition and metabolism of 3-(3-chlorophenoxy)-N-methylpyrrolidine [14C]-carboxamide in the rat, dog, and man.", "content": "Studies with a 14C-labeled sample have shown that the title compound A is readily absorbed and very rapidly excreted by the rat, dog, and man. The metabolites result from aromatic ring hydroxylation, oxidation, and dealkylation of the urea methyl group, and oxidative ring opening of the pyrrolidine ring. Rat metabolites were 3-(3-chloro-4-hydroxyphenoxy)-N-methyl-l-pyrrolidinecarboxamide (C) 3-(3-chloro-4-hydroxyphenoxy)-1-pyrrolidinecarboxamide (D), 3-(3-chlorohydroxyphenoxy)-1-pyrrolidinecarboxamide (E), 3-(3-chlorophenoxy)-4([(methylamino)-carbonyl]amino)butanoic acid (G), 3-(3-chlorophenoxy)-4[(aminocarbonyl)amino]butanoic acid (H). Dog metabolites were C, D, G, and H. Human metabolites were 3-(3-chloro-4-hydroxyphenoxy)-N-formyl-l-pyrrolidinecarboxamide (F), C, D, G, and H. An electron-capture gas chromatographic assay for the parent compound is described. Whole-body autoradiograms of rat slices and the tissue residue data from these slices are reported and indicate rapid tissue depletion of radioactivity.", "contents": "Disposition and metabolism of 3-(3-chlorophenoxy)-N-methylpyrrolidine [14C]-carboxamide in the rat, dog, and man. Studies with a 14C-labeled sample have shown that the title compound A is readily absorbed and very rapidly excreted by the rat, dog, and man. The metabolites result from aromatic ring hydroxylation, oxidation, and dealkylation of the urea methyl group, and oxidative ring opening of the pyrrolidine ring. Rat metabolites were 3-(3-chloro-4-hydroxyphenoxy)-N-methyl-l-pyrrolidinecarboxamide (C) 3-(3-chloro-4-hydroxyphenoxy)-1-pyrrolidinecarboxamide (D), 3-(3-chlorohydroxyphenoxy)-1-pyrrolidinecarboxamide (E), 3-(3-chlorophenoxy)-4([(methylamino)-carbonyl]amino)butanoic acid (G), 3-(3-chlorophenoxy)-4[(aminocarbonyl)amino]butanoic acid (H). Dog metabolites were C, D, G, and H. Human metabolites were 3-(3-chloro-4-hydroxyphenoxy)-N-formyl-l-pyrrolidinecarboxamide (F), C, D, G, and H. An electron-capture gas chromatographic assay for the parent compound is described. Whole-body autoradiograms of rat slices and the tissue residue data from these slices are reported and indicate rapid tissue depletion of radioactivity."}
{"id": "PMID:8295", "title": "Physiological disposition and metabolic fate of a new antiarrhythmic agent, alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl) benzylamine in the rat, dog, monkey, baboon, and man.", "content": "The physiological disposition of a new orally active antiarrhythmic drug, alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl)benzylamine (MK-251) was investigated in the rat, dog, rhesus monkey, baboon, and man. MK-251 was extensively absorbed after oral administration in all species. Fecal excretion was the major route of tracer elimination in the rat (70%) and dog (80%), whereas the monkey, baboon, and man excreted the majority of the dose via the urine (40-80%). MK-251 and/or its metabolites were widely distributed in rat tissues and exhibited tissue/plasma ratios greater than one in most instances. The lung, liver, and kidney possessed a high tissue affinity for drug and metabolites. The plasma and urinary profile of radioactivity indicated extensive metabolism of MK-251 in all species. Less than 5% of the plasma and urinary radioactivity was identified as unchanged drug. In spite of extensive metabolic transformations, a remarkable feature of this drug is its persistence in the plasma for long periods of time. This is thought to be due to tissue affinity. The metabolic pattern for MK-251 was essentially the same in all species. The major metabolites present in the plasma and the urine were identified as the carbinol analog of MK-251, 2-[4-(alpha, alpha, beta, beta-tetrafluorophenethyl)phenyl]-2-propanol (I), and its glucuronide conjugate. Other metabolites characterized in the urine and plasma were: the N-glucuronide of MK-251, 2-[4-(alpha, alpha, beta, beta-tetrafluorophenethyl)phenyl]propene (II), 2-nitro-2-[4-(alpha, alpha, beta, beta-tetrafluorophenethyl)phenyl]propane (III), alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl)benzyl methyl ether (IV-1) and 4-(alpha, alpha, beta, beta-tetrafluorophenethyl), acetophenone (IV-2). Two minor urinary metabolites were tentatively identified as the N-hydroxy analog of MK-251 and the glycol analog of carbinol I. The in vivo formation of the methyl ether represents the first report of alkylation of a tertiary alcohol.", "contents": "Physiological disposition and metabolic fate of a new antiarrhythmic agent, alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl) benzylamine in the rat, dog, monkey, baboon, and man. The physiological disposition of a new orally active antiarrhythmic drug, alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl)benzylamine (MK-251) was investigated in the rat, dog, rhesus monkey, baboon, and man. MK-251 was extensively absorbed after oral administration in all species. Fecal excretion was the major route of tracer elimination in the rat (70%) and dog (80%), whereas the monkey, baboon, and man excreted the majority of the dose via the urine (40-80%). MK-251 and/or its metabolites were widely distributed in rat tissues and exhibited tissue/plasma ratios greater than one in most instances. The lung, liver, and kidney possessed a high tissue affinity for drug and metabolites. The plasma and urinary profile of radioactivity indicated extensive metabolism of MK-251 in all species. Less than 5% of the plasma and urinary radioactivity was identified as unchanged drug. In spite of extensive metabolic transformations, a remarkable feature of this drug is its persistence in the plasma for long periods of time. This is thought to be due to tissue affinity. The metabolic pattern for MK-251 was essentially the same in all species. The major metabolites present in the plasma and the urine were identified as the carbinol analog of MK-251, 2-[4-(alpha, alpha, beta, beta-tetrafluorophenethyl)phenyl]-2-propanol (I), and its glucuronide conjugate. Other metabolites characterized in the urine and plasma were: the N-glucuronide of MK-251, 2-[4-(alpha, alpha, beta, beta-tetrafluorophenethyl)phenyl]propene (II), 2-nitro-2-[4-(alpha, alpha, beta, beta-tetrafluorophenethyl)phenyl]propane (III), alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl)benzyl methyl ether (IV-1) and 4-(alpha, alpha, beta, beta-tetrafluorophenethyl), acetophenone (IV-2). Two minor urinary metabolites were tentatively identified as the N-hydroxy analog of MK-251 and the glycol analog of carbinol I. The in vivo formation of the methyl ether represents the first report of alkylation of a tertiary alcohol."}
{"id": "PMID:8298", "title": "[Treatment of hypertrophic obstructive cardiomyopathy with verapamil, a calcium antagonist (author's transl)].", "content": "Cardiac catheterisation with pressure measurements, left-ventricular cine-angiography and selective coronary angiography confirmed the diagnosis of hypertrophic obstructive cardiomyopathy in 20 patients. After a mean observation period of 20 months during which most of them were treated with beta-blockers, verapamil, 480 mg by mouth, was given for an average of 12 months. There was an impressive improvement in symptoms, compared with the state under beta-blocker treatment. There was a significant reduction in the ECG signs of left-ventricular hypertrophy and of the radiologically measured heart volume. Treatment of this condition with verapamil appeared to be superior to that with beta-blockers.", "contents": "[Treatment of hypertrophic obstructive cardiomyopathy with verapamil, a calcium antagonist (author's transl)]. Cardiac catheterisation with pressure measurements, left-ventricular cine-angiography and selective coronary angiography confirmed the diagnosis of hypertrophic obstructive cardiomyopathy in 20 patients. After a mean observation period of 20 months during which most of them were treated with beta-blockers, verapamil, 480 mg by mouth, was given for an average of 12 months. There was an impressive improvement in symptoms, compared with the state under beta-blocker treatment. There was a significant reduction in the ECG signs of left-ventricular hypertrophy and of the radiologically measured heart volume. Treatment of this condition with verapamil appeared to be superior to that with beta-blockers."}
{"id": "PMID:8296", "title": "Effect of 3-methylcholanthrene pretreatment on the bioavailability of phenacetin in the rat.", "content": "A thin-layer chromatographic procedure is described for the quantitative determination of phenacetin and acetaminophen in rat plasma. The method was used to determine the effect of 3-methylcholanthrene (3-MC) on the disposition and bioavailability of phenacetin following its oral and iv administration to rats. Pretreatment with 3-MC decreased the plasma half-life of phenacetin, after iv administration, from 28 min to 4.5 min and reduced the systemic bioavailability of phenacetin, after oral administration, from 45% in control rats to 6% in 3-MC-treated rats. By comparing the plasma levels of phenacetin in the portal circulation with those in the peripheral circulation, following the oral administration of phenacetin, it was concluded that the 7-fold reduction in the bioavailability of phenacetin observed in 3-MC treated rats was caused by a marked increase in the metabolism of phenacetin during its first pass through the liver.", "contents": "Effect of 3-methylcholanthrene pretreatment on the bioavailability of phenacetin in the rat. A thin-layer chromatographic procedure is described for the quantitative determination of phenacetin and acetaminophen in rat plasma. The method was used to determine the effect of 3-methylcholanthrene (3-MC) on the disposition and bioavailability of phenacetin following its oral and iv administration to rats. Pretreatment with 3-MC decreased the plasma half-life of phenacetin, after iv administration, from 28 min to 4.5 min and reduced the systemic bioavailability of phenacetin, after oral administration, from 45% in control rats to 6% in 3-MC-treated rats. By comparing the plasma levels of phenacetin in the portal circulation with those in the peripheral circulation, following the oral administration of phenacetin, it was concluded that the 7-fold reduction in the bioavailability of phenacetin observed in 3-MC treated rats was caused by a marked increase in the metabolism of phenacetin during its first pass through the liver."}
{"id": "PMID:8297", "title": "Effect of methadone dose on the biliary excretion of methadone metabolites in the rat.", "content": "The effect of three different doses of 14C-methadone (0.08, 1.0 and 2.5 mg/kg) on the biliary excretion of methadone metabolites was studied in the rat. After administration of the 0.08- and 1.0-mg/kg doses of 14C-methadone there was no difference in the percentage of administered 14C excreted into bile with time. However, after the 2.5-mg/kg dose a significant increase was observed in the percentage of administered 14C excreted into bile. Analysis of bile samples showed that this increase was due to increases in the biliary excretion of two of the major metabolites of methadone. Several mechanisms could be responsible for this disproportionate increase in biliary excretion of methadone metabolites after high doses of methadone. It was found that the effect of high methadone dose on the biliary excretion of its metabolites was nearly eliminated when studied in phenobarbital (PB)-pretreated rats. Pretreatment of rats with PB increases the biliary excretion of methadone metabolites, primarily by increasing rates of methadone metabolism. The lack of additivity of the effect of the high dose of methadone and PB pretreatment on the biliary excretion of methadone metabolites suggests that a high dose of methadone also stimulates methadone metabolism, which results in the observed increased percentage of the administered dose excreted into bile.", "contents": "Effect of methadone dose on the biliary excretion of methadone metabolites in the rat. The effect of three different doses of 14C-methadone (0.08, 1.0 and 2.5 mg/kg) on the biliary excretion of methadone metabolites was studied in the rat. After administration of the 0.08- and 1.0-mg/kg doses of 14C-methadone there was no difference in the percentage of administered 14C excreted into bile with time. However, after the 2.5-mg/kg dose a significant increase was observed in the percentage of administered 14C excreted into bile. Analysis of bile samples showed that this increase was due to increases in the biliary excretion of two of the major metabolites of methadone. Several mechanisms could be responsible for this disproportionate increase in biliary excretion of methadone metabolites after high doses of methadone. It was found that the effect of high methadone dose on the biliary excretion of its metabolites was nearly eliminated when studied in phenobarbital (PB)-pretreated rats. Pretreatment of rats with PB increases the biliary excretion of methadone metabolites, primarily by increasing rates of methadone metabolism. The lack of additivity of the effect of the high dose of methadone and PB pretreatment on the biliary excretion of methadone metabolites suggests that a high dose of methadone also stimulates methadone metabolism, which results in the observed increased percentage of the administered dose excreted into bile."}
{"id": "PMID:8301", "title": "[Studies on optimising rubella virus haemagglutination-inhibitor tests].", "content": "Immuno-electrophoretic and serological studies were undertaken to characterise the non-specific serum inhibitor of rubella haemagglutination. The majority of such inhibitor effects come from the beta(1)-lipoproteins. In addition, small inhibitory effects which were due to alpha(1)-lipoproteins were noted in some sera. The result of the tests is influenced less by removing the inhibitor than by conditions of incubation of the serum-antigen mixture, especially pH. The test is more sensitive if it is not performed at optimal pH for haemagglutination.", "contents": "[Studies on optimising rubella virus haemagglutination-inhibitor tests]. Immuno-electrophoretic and serological studies were undertaken to characterise the non-specific serum inhibitor of rubella haemagglutination. The majority of such inhibitor effects come from the beta(1)-lipoproteins. In addition, small inhibitory effects which were due to alpha(1)-lipoproteins were noted in some sera. The result of the tests is influenced less by removing the inhibitor than by conditions of incubation of the serum-antigen mixture, especially pH. The test is more sensitive if it is not performed at optimal pH for haemagglutination."}
{"id": "PMID:8306", "title": "Inactivation of porcine calcitonin by rat kidney microsome.", "content": "Biological activity of porcine calcitonin was most actively inactivated by the rat kidney homogenate than by other tissue homogenates. Among the various subcellular fractions of the rat kidney homogenate examined, microsome fraction was most active in the in vitro inactivation of porcine calcitonin. Inactivation of porcine calcitonin by the rat kidney microsome was dependent on pH and temperature. Inactivating activity of the rat kidney microsome was inhibited by 1 X 10(-3) M monoiodoacetate and 1 X10(-5) M p-chloromercuribenzoate. These results suggest that porcine calcitonin is probably inactivated by a SH-enzyme in the rat kidney microsomes. However, the participation of other enzymes cannot be ruled out, since the inactivating activity of the rat kidney microsome fraction is also inhibited by 1 X 10(-4) M diisopropylfuorophosphate.", "contents": "Inactivation of porcine calcitonin by rat kidney microsome. Biological activity of porcine calcitonin was most actively inactivated by the rat kidney homogenate than by other tissue homogenates. Among the various subcellular fractions of the rat kidney homogenate examined, microsome fraction was most active in the in vitro inactivation of porcine calcitonin. Inactivation of porcine calcitonin by the rat kidney microsome was dependent on pH and temperature. Inactivating activity of the rat kidney microsome was inhibited by 1 X 10(-3) M monoiodoacetate and 1 X10(-5) M p-chloromercuribenzoate. These results suggest that porcine calcitonin is probably inactivated by a SH-enzyme in the rat kidney microsomes. However, the participation of other enzymes cannot be ruled out, since the inactivating activity of the rat kidney microsome fraction is also inhibited by 1 X 10(-4) M diisopropylfuorophosphate."}
{"id": "PMID:8307", "title": "Estimation of testosterone binding capacity in the serum with hydrophobie resin.", "content": "A method for the estimation of the serum testosterone binding capacity (TeBC) using hydrophobic resin, Amberlite XAD-2, was developed. The serum was incubated with a saturating amount of testosterone-1,2(-3)H at 15 degrees C, unbound testosterone was adsorbed to the resin and the 3H-radoiactivity remaining in the supernatant fluid was counted. Under these conditions, the normal levels and their standard deviations were 15.08+/-3.39 ng/ml (n=7) for male and 35.06+/-3.56 ng/ml (n=6) for female respectively. Precision of the method was 6.29%. TeBC in the third month of pregnancy was approximately 1.5 times more than that of non-pregnant women, and approximately 3 to 5 times in the tenth month.", "contents": "Estimation of testosterone binding capacity in the serum with hydrophobie resin. A method for the estimation of the serum testosterone binding capacity (TeBC) using hydrophobic resin, Amberlite XAD-2, was developed. The serum was incubated with a saturating amount of testosterone-1,2(-3)H at 15 degrees C, unbound testosterone was adsorbed to the resin and the 3H-radoiactivity remaining in the supernatant fluid was counted. Under these conditions, the normal levels and their standard deviations were 15.08+/-3.39 ng/ml (n=7) for male and 35.06+/-3.56 ng/ml (n=6) for female respectively. Precision of the method was 6.29%. TeBC in the third month of pregnancy was approximately 1.5 times more than that of non-pregnant women, and approximately 3 to 5 times in the tenth month."}
{"id": "PMID:8308", "title": "Dynamic asymmetries in liver tyrosine aminotransferase induction.", "content": "Changes in liver tyrosine aminotransferase activity were measured in mice and rats following a whole body X-irradiation in order to ascertain the dose-effect relationship. The response was either (1) linear in case of low pulses (25 rad/min); (2) parabolic, indicating the onset of a saturation process in case of medium pulses (60 rad/min), or (3) biphasic, suggesting the cooperation of at least two regulatory mechanisms following longtime exposure to strong stimuli (100 rad/min).", "contents": "Dynamic asymmetries in liver tyrosine aminotransferase induction. Changes in liver tyrosine aminotransferase activity were measured in mice and rats following a whole body X-irradiation in order to ascertain the dose-effect relationship. The response was either (1) linear in case of low pulses (25 rad/min); (2) parabolic, indicating the onset of a saturation process in case of medium pulses (60 rad/min), or (3) biphasic, suggesting the cooperation of at least two regulatory mechanisms following longtime exposure to strong stimuli (100 rad/min)."}
{"id": "PMID:8309", "title": "Amino acid metabolizing enzymes in rat submaxillary gland, normal or neoplastic, and in pancreas.", "content": "The activities of 12 enzymes, many related to ornithine metabolism, were measured in rat submaxillary gland, submaxillary gland tumors and pancreas. In submaxillary gland, the activities of arginase, ornithine aminotransferase, pyrroline-5-carboxylate reductase and glutamine synthetase were high, but no ornithine transcarbamylase or proline oxidase could be detected. In the fetal submaxillary gland, arginase was at almost adult levels while ornithine aminotransferase reached 50% of its adult value postnatally. Submaxillary tumors deviated from their cognate tissue by lower levels of amino acid metabolizing enzymes and by high concentrations of thymidine kinase. In pancreas, none of the pyrroline-5-carboxylate metabolizing enzymes were as high as in either liver or submaxillary gland. The outstanding activities were those of gamma-glutamyl transpeptidase and glutamate dehydrogenase. Although arginase activities in submaxillary gland and pancreas were quantitatively similar, they differed qualitatively: submaxillary gland contained the same variant as liver while the pancreatic isozymes resembled those of other nonhepatic tissues.", "contents": "Amino acid metabolizing enzymes in rat submaxillary gland, normal or neoplastic, and in pancreas. The activities of 12 enzymes, many related to ornithine metabolism, were measured in rat submaxillary gland, submaxillary gland tumors and pancreas. In submaxillary gland, the activities of arginase, ornithine aminotransferase, pyrroline-5-carboxylate reductase and glutamine synthetase were high, but no ornithine transcarbamylase or proline oxidase could be detected. In the fetal submaxillary gland, arginase was at almost adult levels while ornithine aminotransferase reached 50% of its adult value postnatally. Submaxillary tumors deviated from their cognate tissue by lower levels of amino acid metabolizing enzymes and by high concentrations of thymidine kinase. In pancreas, none of the pyrroline-5-carboxylate metabolizing enzymes were as high as in either liver or submaxillary gland. The outstanding activities were those of gamma-glutamyl transpeptidase and glutamate dehydrogenase. Although arginase activities in submaxillary gland and pancreas were quantitatively similar, they differed qualitatively: submaxillary gland contained the same variant as liver while the pancreatic isozymes resembled those of other nonhepatic tissues."}
{"id": "PMID:8310", "title": "Relationships of femoral venous [K+], PO2, osmolality, and [orthophosphate) with heart rate, ventilation, and leg blood flow during bicycle exercise in athletes and non-athletes.", "content": "The relationship of femoral venous [K+], [H+], osmolality (OSM), PO2, and [inorganic phosphate] ([Pi]) with heart rate (HR), ventilation (VE), and calculated leg blood flow (Q) were investigated during bicycle exercise in endurance trained (TR) and untrained (UT) test subjects. At a given VO2 the increases of [K+], OSM, [Pi] and the decrease of PO2 were significantly lower in TR than in UT. In the same proportion the increases of HR, VE, and Q were diminished. Thus in TR and UT identical and highly significantly correlated regression lines of [K+], [H+], OSM, [Pi] and PO2 with HR, VE, and Q were obtained. These constituents changed in the same proportion as the relative VO2 in TR and UT. No relationships with [Na+], [Ca++], and [ Mg++] were found. By means of a multiple regression analysis the partial influence of K+, H+, OSM, PO2, and Pi upon the total change of HR, VE and Q was estimated to compare with data from infusion experiments. The findings were discussed in view of the hypothesis that these candidates may provide linkage between metabolic events, circulatory, and ventilatory adjustments during work.", "contents": "Relationships of femoral venous [K+], PO2, osmolality, and [orthophosphate) with heart rate, ventilation, and leg blood flow during bicycle exercise in athletes and non-athletes. The relationship of femoral venous [K+], [H+], osmolality (OSM), PO2, and [inorganic phosphate] ([Pi]) with heart rate (HR), ventilation (VE), and calculated leg blood flow (Q) were investigated during bicycle exercise in endurance trained (TR) and untrained (UT) test subjects. At a given VO2 the increases of [K+], OSM, [Pi] and the decrease of PO2 were significantly lower in TR than in UT. In the same proportion the increases of HR, VE, and Q were diminished. Thus in TR and UT identical and highly significantly correlated regression lines of [K+], [H+], OSM, [Pi] and PO2 with HR, VE, and Q were obtained. These constituents changed in the same proportion as the relative VO2 in TR and UT. No relationships with [Na+], [Ca++], and [ Mg++] were found. By means of a multiple regression analysis the partial influence of K+, H+, OSM, PO2, and Pi upon the total change of HR, VE and Q was estimated to compare with data from infusion experiments. The findings were discussed in view of the hypothesis that these candidates may provide linkage between metabolic events, circulatory, and ventilatory adjustments during work."}
{"id": "PMID:8311", "title": "On the transport of tripeptide antibiotics in bacteria.", "content": "The two tripeptide antibiotics L-2-amino-4-methylphosphinobutyryl-alanyl-alanyl-alanine (L-phosphinothricyl-alanyl-alanine) and L-(N5-phosphono)methionine-S-sulfoximinyl-alanyl-alanine, both inhibitors of the glutamine synthetase, are transported into the cell of Escherichia coli K 12 via the oligopeptide transport system. The uptake by this system is proved first of all by cross-resistance with tri-L-ornithine using oligopeptide-transport-deficient mutants, and secondly by antagonism tests demonstrating competitive reversal of the action of the antibiotic by several peptides which have been shown to be transported via the oligopeptide transport system, e.g. tri-L-alanine, tetra-L-alanine, tri-L-lysine, tri-L-serine, tri-glycine, glycyl-glycyl-L-alanine and the synthetic tripeptide L-azadenyl-aminohexanoyl-alanyl-alanine. On the other hand, there is no effect on the action of the antibiotic in antagonism tests with compounds which use different transport systems, such as L-alanyl-alanine, L-lysyl-lysine, glutathione and the synthetic amino acid azaadenylaminohexanoic acid, i.e. 2-amino-6-(7-amino-3H-v-triazolo-[4,5-d]-pyrimidin-3-yl)hexanoic acid. Another inhibitor of the glutamine synthetase, L-methionine-S-dioxide (methioninesulfone) could be converted into a tripeptide form by linkage to L-alanyl-alanine analogously to the tripeptide antibiotics described above. Whereas the free L-methionine-S-dioxide seems to be transported via the methionine transport system, the tripeptide form is transported via the oligopeptide transport system. Thus, this glutamine synthetase inhibitor can be taken up by the cell via two different transport mechanisms. Our results indicate that this could provide a synergistic effect. The syntheses of the new tripeptides L-azaadenylaminohexanoyl-alanyl-alanine and L-methionine-S-dioxidyl-alanyl-alanine were performed by dicyclohexylcarbodiimide couplings of the unusual N-protected L-alpha-amino acids azaadenylaminohexanoic acid and L-methionine-S-dioxide to L-alanyl-alanine-tert-butyl ester followed by common deprotection steps. Tri-L-ornithine was synthesized without carboxyl protection via two successive couplings of hydroxybenzotriazol esters of Nalpha-butoxycarbonyl-Ndelta-benzyloxycarbonyl-L-ornithine.", "contents": "On the transport of tripeptide antibiotics in bacteria. The two tripeptide antibiotics L-2-amino-4-methylphosphinobutyryl-alanyl-alanyl-alanine (L-phosphinothricyl-alanyl-alanine) and L-(N5-phosphono)methionine-S-sulfoximinyl-alanyl-alanine, both inhibitors of the glutamine synthetase, are transported into the cell of Escherichia coli K 12 via the oligopeptide transport system. The uptake by this system is proved first of all by cross-resistance with tri-L-ornithine using oligopeptide-transport-deficient mutants, and secondly by antagonism tests demonstrating competitive reversal of the action of the antibiotic by several peptides which have been shown to be transported via the oligopeptide transport system, e.g. tri-L-alanine, tetra-L-alanine, tri-L-lysine, tri-L-serine, tri-glycine, glycyl-glycyl-L-alanine and the synthetic tripeptide L-azadenyl-aminohexanoyl-alanyl-alanine. On the other hand, there is no effect on the action of the antibiotic in antagonism tests with compounds which use different transport systems, such as L-alanyl-alanine, L-lysyl-lysine, glutathione and the synthetic amino acid azaadenylaminohexanoic acid, i.e. 2-amino-6-(7-amino-3H-v-triazolo-[4,5-d]-pyrimidin-3-yl)hexanoic acid. Another inhibitor of the glutamine synthetase, L-methionine-S-dioxide (methioninesulfone) could be converted into a tripeptide form by linkage to L-alanyl-alanine analogously to the tripeptide antibiotics described above. Whereas the free L-methionine-S-dioxide seems to be transported via the methionine transport system, the tripeptide form is transported via the oligopeptide transport system. Thus, this glutamine synthetase inhibitor can be taken up by the cell via two different transport mechanisms. Our results indicate that this could provide a synergistic effect. The syntheses of the new tripeptides L-azaadenylaminohexanoyl-alanyl-alanine and L-methionine-S-dioxidyl-alanyl-alanine were performed by dicyclohexylcarbodiimide couplings of the unusual N-protected L-alpha-amino acids azaadenylaminohexanoic acid and L-methionine-S-dioxide to L-alanyl-alanine-tert-butyl ester followed by common deprotection steps. Tri-L-ornithine was synthesized without carboxyl protection via two successive couplings of hydroxybenzotriazol esters of Nalpha-butoxycarbonyl-Ndelta-benzyloxycarbonyl-L-ornithine."}
{"id": "PMID:8312", "title": "Yeast hexokinase: substrate-induced association--dissociation reactions in the binding of glucose to hexokinase P-II.", "content": "A method is described for the purification of native hexokinases P-I and P-II from yeast using preparative isoelectric focussing to separate the isozymes. The binding of glucose to hexokinase P-II, and the effect of this on the monomer--dimer association--dissociation reaction have been investigated quantitatively by a combination of titrations of intrinsic protein fluorescence and equilibrium ultracentrifugation. Association constants for the monomer-dimer reaction decreased with increasing pH, ionic strength and concentration of glucose. Saturating concentrations of glucose did not bring about complete dissociation of the enzyme showing that both sites were occupired in the dimer. At pH 8.0 and high ionic strength, where the enzyme existed as monomer, the dissociation constant of the enzyme-glucose complex was 3 X 10(-4) mol 1(-1) and was independent of the concentration of enzyme. Binding to the dimeric form at low pH and ionic strength (I=0.02 mol 1(-1), pH less than 7.5) was also independent of enzyme concentration (in the range 10-1000 mug ml-1) but was much weaker. The process could be described by a single dissociation constant, showing that the two available sites on the dimer were equivalent and non-cooperative; values of the intrinsic dissociation constant varied from 2.5 X 10(-3) mol 1(-1) at pH 7.0 to 6 X 10(-3) at pH 6.5. Under intermediate conditions (pH 7.0, ionic strength=0.15 mol 1(-1)), where monomer and dimer coexisted, the binding of glucose showed weak positive cooperatively (Hill coefficient 1.2); in addition, the binding was dependent upon the concentration of enzyme in the direction of stronger binding at lower concentrations. The results show that the phenomenon of half-sites reactivity observed in the binding of glucose to crystalline hexokinase P-II does not occur in solution; the simplest explanation of our finding the two sites to be equivalent is that the dimer results from the homologous association of two identical subunits.", "contents": "Yeast hexokinase: substrate-induced association--dissociation reactions in the binding of glucose to hexokinase P-II. A method is described for the purification of native hexokinases P-I and P-II from yeast using preparative isoelectric focussing to separate the isozymes. The binding of glucose to hexokinase P-II, and the effect of this on the monomer--dimer association--dissociation reaction have been investigated quantitatively by a combination of titrations of intrinsic protein fluorescence and equilibrium ultracentrifugation. Association constants for the monomer-dimer reaction decreased with increasing pH, ionic strength and concentration of glucose. Saturating concentrations of glucose did not bring about complete dissociation of the enzyme showing that both sites were occupired in the dimer. At pH 8.0 and high ionic strength, where the enzyme existed as monomer, the dissociation constant of the enzyme-glucose complex was 3 X 10(-4) mol 1(-1) and was independent of the concentration of enzyme. Binding to the dimeric form at low pH and ionic strength (I=0.02 mol 1(-1), pH less than 7.5) was also independent of enzyme concentration (in the range 10-1000 mug ml-1) but was much weaker. The process could be described by a single dissociation constant, showing that the two available sites on the dimer were equivalent and non-cooperative; values of the intrinsic dissociation constant varied from 2.5 X 10(-3) mol 1(-1) at pH 7.0 to 6 X 10(-3) at pH 6.5. Under intermediate conditions (pH 7.0, ionic strength=0.15 mol 1(-1)), where monomer and dimer coexisted, the binding of glucose showed weak positive cooperatively (Hill coefficient 1.2); in addition, the binding was dependent upon the concentration of enzyme in the direction of stronger binding at lower concentrations. The results show that the phenomenon of half-sites reactivity observed in the binding of glucose to crystalline hexokinase P-II does not occur in solution; the simplest explanation of our finding the two sites to be equivalent is that the dimer results from the homologous association of two identical subunits."}
{"id": "PMID:8313", "title": "Affinity chromatography and binding studies on immobilized 5'-monophosphate and adenosine 2',5'-bisphosphate of nicotinamide nucleotide transhydrogenase from Pseudomonas aeruginosa.", "content": "1. Nicotinamide nucleotide transhydrogenase from Pseudomonas aeruginosa was purified to apparent homogeneity with an improved method employing affinity chromatography on N6-(6aminohexyl)-adenosine 2', 5'-bisphosphate-Sepharose 4B. 2. Polyacrylamide gel electrophoresis of the purified transhydrogenase carried out in the presence of sodium dodecyl sulphate, indicated a minimal molecular weight of 55000 +/- 2000. 3. The kinetic and regulatory properties of the purified transhydrogenase resembled those of the crude enzyme, i.e., NADPH, adenosine 2'-monophosphate and Ca2+ were activators whereas NADP+ was inhibitory. 4. Nicotinamide nucleotide-specific release of binding of the transhydrogenase to N6-(6-aminohexyl)-adenosine-2',5'-bisphosphate-Sepharose and N6-(-aminohexyl)-adenosine-5'-monophosphate-Sepharose suggests the presence of at least two separate binding sites for nicotinamide nucleotides, one that is specific for NADP(H) and one that binds both NAD(H) and NADP(H). 5. Binding of transhydrogenase to N6-)6-aminohexyl)-adenosine-2',5'-bisphosphate-Sepharose and activation of the enzyme by adenosine-2',5'-bisphophate showed a marked pH dependence. In contrast, inhibition of the Ca2+-activated enzyme by adenosine 2',5'-bisphosphate was virtually constant at various pH values. This descrepancy was interpreted to indicate the existence of separate nucleotide-binding effector and active sites.", "contents": "Affinity chromatography and binding studies on immobilized 5'-monophosphate and adenosine 2',5'-bisphosphate of nicotinamide nucleotide transhydrogenase from Pseudomonas aeruginosa. 1. Nicotinamide nucleotide transhydrogenase from Pseudomonas aeruginosa was purified to apparent homogeneity with an improved method employing affinity chromatography on N6-(6aminohexyl)-adenosine 2', 5'-bisphosphate-Sepharose 4B. 2. Polyacrylamide gel electrophoresis of the purified transhydrogenase carried out in the presence of sodium dodecyl sulphate, indicated a minimal molecular weight of 55000 +/- 2000. 3. The kinetic and regulatory properties of the purified transhydrogenase resembled those of the crude enzyme, i.e., NADPH, adenosine 2'-monophosphate and Ca2+ were activators whereas NADP+ was inhibitory. 4. Nicotinamide nucleotide-specific release of binding of the transhydrogenase to N6-(6-aminohexyl)-adenosine-2',5'-bisphosphate-Sepharose and N6-(-aminohexyl)-adenosine-5'-monophosphate-Sepharose suggests the presence of at least two separate binding sites for nicotinamide nucleotides, one that is specific for NADP(H) and one that binds both NAD(H) and NADP(H). 5. Binding of transhydrogenase to N6-)6-aminohexyl)-adenosine-2',5'-bisphosphate-Sepharose and activation of the enzyme by adenosine-2',5'-bisphophate showed a marked pH dependence. In contrast, inhibition of the Ca2+-activated enzyme by adenosine 2',5'-bisphosphate was virtually constant at various pH values. This descrepancy was interpreted to indicate the existence of separate nucleotide-binding effector and active sites."}
{"id": "PMID:8314", "title": "Somatic antigens of shigella. Structural investigation on the O-specific polysaccharide chain of Shigella dysenteriae type 1 lipopolysaccharide.", "content": "The O-specific polysaccharide obtained from the lipopolysaccharide of Shigella dysenteriae type 1 (Shigella shiga) by mild acid hydrolysis followed by fractionation on Sephadex G-50 was found to be identical to that desribed by Morgan's group and was composed of L-rhamnose, D-galactose and N-acetyl-D-glycosamine in a ratio 2:1:1. On the basis of methylation analysis data the polysaccharide was proved to be a linear chain of monosaccharide residues in pyranose forms substituted at position 3, except for that of galactose substituted at position 2. Selective cleavage, based on the N-deacetylation reaction of the polymer, together with determination of linkage configurations by chromic anhydride oxidation showed that the O-specific polysaccharide is built up of repeating tetrasaccharide units whose proposed structure is given below -3)-alpha-L-Rhap (1-3)-alpha-L-Rhap(1-2)-alpha-D-Galp(1-3)-alphapD-GlcNAcp(1- where RHAP = rhamnopyranose, Galp = galactopyranose, and GlcNAcp = N-acetyl-glucosamine. The present findings confirmed the considerations of Heidelberger on the substitution patterns of L-rhamnose and D-galactose residues from the results of serological studies.", "contents": "Somatic antigens of shigella. Structural investigation on the O-specific polysaccharide chain of Shigella dysenteriae type 1 lipopolysaccharide. The O-specific polysaccharide obtained from the lipopolysaccharide of Shigella dysenteriae type 1 (Shigella shiga) by mild acid hydrolysis followed by fractionation on Sephadex G-50 was found to be identical to that desribed by Morgan's group and was composed of L-rhamnose, D-galactose and N-acetyl-D-glycosamine in a ratio 2:1:1. On the basis of methylation analysis data the polysaccharide was proved to be a linear chain of monosaccharide residues in pyranose forms substituted at position 3, except for that of galactose substituted at position 2. Selective cleavage, based on the N-deacetylation reaction of the polymer, together with determination of linkage configurations by chromic anhydride oxidation showed that the O-specific polysaccharide is built up of repeating tetrasaccharide units whose proposed structure is given below -3)-alpha-L-Rhap (1-3)-alpha-L-Rhap(1-2)-alpha-D-Galp(1-3)-alphapD-GlcNAcp(1- where RHAP = rhamnopyranose, Galp = galactopyranose, and GlcNAcp = N-acetyl-glucosamine. The present findings confirmed the considerations of Heidelberger on the substitution patterns of L-rhamnose and D-galactose residues from the results of serological studies."}
{"id": "PMID:8315", "title": "Purification and properties of 3-hexulosephosphate synthase from Methylomonas M 15.", "content": "3-Hexulosephosphate synthase, the first enzyme of the ribulose monophosphate cycle, was purified 15-fold from methanol-grown Methylomonas M 15. The purification procedure involved chromatography on DEAE-cellulose, Sephadex G-75, and DEAE-Sephadex A-50. The purified enzyme was more than 95% pure as judged by analytical polyacrylamide gel electrophoresis. The molecular weight was calculated to be 43000 from sedimentation equilibrium experiments. Electrophoresis in sodium dodecylsulfate gels gave a single band corresponding to a molecular weight of 22000. The enzyme catalyzes specifically the condensation formaldehyde with ribulose 5-phosphate to yield D-arabino-3-hexulose 6-phosphate. The Km values were found to be 1.1 mM for formaldehyde and 1.6 mM for ribulose 5-phosphate. A bivalent cation is essential for activity and stability of the enzyme, Mg2+ and Mn2+ serve best for this purpose. The optimum of pH for enzyme activity is 7.5--8.0.", "contents": "Purification and properties of 3-hexulosephosphate synthase from Methylomonas M 15. 3-Hexulosephosphate synthase, the first enzyme of the ribulose monophosphate cycle, was purified 15-fold from methanol-grown Methylomonas M 15. The purification procedure involved chromatography on DEAE-cellulose, Sephadex G-75, and DEAE-Sephadex A-50. The purified enzyme was more than 95% pure as judged by analytical polyacrylamide gel electrophoresis. The molecular weight was calculated to be 43000 from sedimentation equilibrium experiments. Electrophoresis in sodium dodecylsulfate gels gave a single band corresponding to a molecular weight of 22000. The enzyme catalyzes specifically the condensation formaldehyde with ribulose 5-phosphate to yield D-arabino-3-hexulose 6-phosphate. The Km values were found to be 1.1 mM for formaldehyde and 1.6 mM for ribulose 5-phosphate. A bivalent cation is essential for activity and stability of the enzyme, Mg2+ and Mn2+ serve best for this purpose. The optimum of pH for enzyme activity is 7.5--8.0."}
{"id": "PMID:8316", "title": "Interest of isoproterenol in the treatment of hemorrhagic shock in dogs.", "content": "Four groups of experiments were focused on two problems: first, the replacement of the substracted amount of blood, and second, the correction of the peripheral reactions to substantial blood loss, namely vasoconstriction and acidosis. We stuck to a simple plan in our experiments: lost blood was entirely collected and retransfused. In 26 cases out of 37, we used isoproterenol hydrochloride (Isuprel - WINTHROP) to open the peripheral vascular bed. In six different groups, we followed the response to variations of retranfusion and administration of isoproterenol. Several parameters were studied: arterial blood pressure, central venous pressure, rectal temperature and pH. The association of blood transfusion with injection of isoproterenol, in adequate amounts to correct hypovolemia and to prevent vasoconstriction, is undoubtedly the best treatment of hemorrhagic shock.", "contents": "Interest of isoproterenol in the treatment of hemorrhagic shock in dogs. Four groups of experiments were focused on two problems: first, the replacement of the substracted amount of blood, and second, the correction of the peripheral reactions to substantial blood loss, namely vasoconstriction and acidosis. We stuck to a simple plan in our experiments: lost blood was entirely collected and retransfused. In 26 cases out of 37, we used isoproterenol hydrochloride (Isuprel - WINTHROP) to open the peripheral vascular bed. In six different groups, we followed the response to variations of retranfusion and administration of isoproterenol. Several parameters were studied: arterial blood pressure, central venous pressure, rectal temperature and pH. The association of blood transfusion with injection of isoproterenol, in adequate amounts to correct hypovolemia and to prevent vasoconstriction, is undoubtedly the best treatment of hemorrhagic shock."}
{"id": "PMID:8317", "title": "The noradrenergic cyclic AMP generating system in the limbic forebrain: pharmacological characterization in vitro and possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics.", "content": "The cyclic AMP generating system in slices of the rat limbic forebrain was investigated. In consists of: (u) A noradrenergic system which responds to norepinephrine (NE) and isoproterenol. Though the rise of the nucleotide elicited by isoproterenol is more rapid than that caused by NE, the maximal effect is less than half of that induced by NE; (2) an adenosine-dependent system. The noradrenergic cyclic AMP generating system in the limbic forebrain displays a number of properties of a central NE receptor: it develops supersensitivity to NE and isoproterenol following prolonged deprivation of NE at postsynaptic sites (chronic treatment with reserpine or chemosympathectomy with 6-hydroxydopamine). When noradrenergic terminals are protected from 6-hydroxydopamine by desmethylimipramine, the responses to NE are not enhanced. Responses to NE are blocked by both propranolol and phentolamine, while responses to isoproterenol are blocked by propranolol but not by phentolamine. The adenosine-dependent system does not develop supersensitivity after central chemosympathectomy and is not blocked by either alpha- or beta-antagonists. While not altering the basal level of the nucleotide, clinically effective antipsychotic drugs caused a dose-dependent inhibition of the limbic noradrenergic cyclic AMP response with clozapine and pimozide being particularly potent (IC50 0.06 and 0.08 muM, respectively). Antipsychotic drugs do, however, not affect cyclic AMP responses elicited by adenosine. The results are compatible with the view that the central NE receptor is closely related to or may be an integral part of an adenylate cyclase system and that its blockade in the limbic forebrain by antipsychotic drugs may contribute to their therapeutic action.", "contents": "The noradrenergic cyclic AMP generating system in the limbic forebrain: pharmacological characterization in vitro and possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics. The cyclic AMP generating system in slices of the rat limbic forebrain was investigated. In consists of: (u) A noradrenergic system which responds to norepinephrine (NE) and isoproterenol. Though the rise of the nucleotide elicited by isoproterenol is more rapid than that caused by NE, the maximal effect is less than half of that induced by NE; (2) an adenosine-dependent system. The noradrenergic cyclic AMP generating system in the limbic forebrain displays a number of properties of a central NE receptor: it develops supersensitivity to NE and isoproterenol following prolonged deprivation of NE at postsynaptic sites (chronic treatment with reserpine or chemosympathectomy with 6-hydroxydopamine). When noradrenergic terminals are protected from 6-hydroxydopamine by desmethylimipramine, the responses to NE are not enhanced. Responses to NE are blocked by both propranolol and phentolamine, while responses to isoproterenol are blocked by propranolol but not by phentolamine. The adenosine-dependent system does not develop supersensitivity after central chemosympathectomy and is not blocked by either alpha- or beta-antagonists. While not altering the basal level of the nucleotide, clinically effective antipsychotic drugs caused a dose-dependent inhibition of the limbic noradrenergic cyclic AMP response with clozapine and pimozide being particularly potent (IC50 0.06 and 0.08 muM, respectively). Antipsychotic drugs do, however, not affect cyclic AMP responses elicited by adenosine. The results are compatible with the view that the central NE receptor is closely related to or may be an integral part of an adenylate cyclase system and that its blockade in the limbic forebrain by antipsychotic drugs may contribute to their therapeutic action."}
{"id": "PMID:8318", "title": "Effect of propranolol of vascular responses to sympathetic nerve stimulation and plasma renin activity in mongrel dogs.", "content": "I.v administration of propranolol (0.2 mg/kg and 1.0 mg/kg) to pentobarbital-anesthetized dogs produced blockade of cardiac beta-receptors and a significant decrease in heart rate. However, only the higher dose of propranolol demonstrated a significant hypotensive effect. Furthermore, this hypotensive action of propranolol was not associated with either adrenergic neruron blockade or changes in plasma renin activity. These results indicate that the initial hypotensive action of propranolol in mongrel dogs is not due to the blockade of beta-receptors, alterations in peripheral sympathetic nervous transmission or plasma renin activity. On the other hand, the action that propranolol is reported to have within the central system may play an important role in accounting for the acute blood pressure lowering action of the compound in mongrel dogs.", "contents": "Effect of propranolol of vascular responses to sympathetic nerve stimulation and plasma renin activity in mongrel dogs. I.v administration of propranolol (0.2 mg/kg and 1.0 mg/kg) to pentobarbital-anesthetized dogs produced blockade of cardiac beta-receptors and a significant decrease in heart rate. However, only the higher dose of propranolol demonstrated a significant hypotensive effect. Furthermore, this hypotensive action of propranolol was not associated with either adrenergic neruron blockade or changes in plasma renin activity. These results indicate that the initial hypotensive action of propranolol in mongrel dogs is not due to the blockade of beta-receptors, alterations in peripheral sympathetic nervous transmission or plasma renin activity. On the other hand, the action that propranolol is reported to have within the central system may play an important role in accounting for the acute blood pressure lowering action of the compound in mongrel dogs."}
{"id": "PMID:8319", "title": "Hypotensive responses following oral adminstration of beta-adrenoceptor blocking drugs to the conscious cat.", "content": "On oral administration, the non-selective beta-adrenoceptor blocking drugs (+/-)-bufuralol, (-)-bufuralol, propanolol, oxprenolol, pindolol and alprenolol produced hypotensive responses in the conscious cat; (+)-bufuralol was without effect. The selective beta-adrenoceptor blocking drugs practolol and atenolol had no effect on blood pressure but tolamolol elicited a hypotensive response. All the drugs tested reduced the tachycardia due to intravenous isoprenaline in the conscious cat; however, not all doses of these drugs reduced blood pressure. (+)-Bufuralol was devoid to beta-adrenoceptive blocking activity. Only tolamolol reduced the pressor response to i.v. phenylephrine in the conscious cat, indicating that alpha-adrenoceptive blocking activity may contribute to its hypotensive action. The results suggest that beta-adrenoceptive blocking activity is necessary for the hypotensive responses of these drugs. However, for the different drugs, there was no correlation between peripheral beta-adrenoceptive blocking activity and hypotensive response.", "contents": "Hypotensive responses following oral adminstration of beta-adrenoceptor blocking drugs to the conscious cat. On oral administration, the non-selective beta-adrenoceptor blocking drugs (+/-)-bufuralol, (-)-bufuralol, propanolol, oxprenolol, pindolol and alprenolol produced hypotensive responses in the conscious cat; (+)-bufuralol was without effect. The selective beta-adrenoceptor blocking drugs practolol and atenolol had no effect on blood pressure but tolamolol elicited a hypotensive response. All the drugs tested reduced the tachycardia due to intravenous isoprenaline in the conscious cat; however, not all doses of these drugs reduced blood pressure. (+)-Bufuralol was devoid to beta-adrenoceptive blocking activity. Only tolamolol reduced the pressor response to i.v. phenylephrine in the conscious cat, indicating that alpha-adrenoceptive blocking activity may contribute to its hypotensive action. The results suggest that beta-adrenoceptive blocking activity is necessary for the hypotensive responses of these drugs. However, for the different drugs, there was no correlation between peripheral beta-adrenoceptive blocking activity and hypotensive response."}
{"id": "PMID:8320", "title": "A kinetic analysis of a catechol-specific binding site in the microsomal fraction from the rabbit aorta.", "content": "(-)-3/-Norepinephrine (3H-NE) binding to the microsomal fraction of the rabbit aorta has been studied. Binding appears to increase linearly with time up to at least 30 min, shows no evidence of stereoselectivity and may be inhibited only by compounds possessing the catechol or 3-methoxy-4hydroxyphenyl moieties, with the latter being 100-fold less effective. 3H-NE binding is saturable with a Km of 8.5 X 10(-8) M and V max of 28 pmoles/mg protein. A Hill plot indicates that binding is noncooperative whereas a Scatchard plot suggests that two sites may be present. Binding does not appear to require physiological concentrations of Ca2+ or Mg2+ and is inhibited significantly by EDTA and sodium metabisulfite. In addition, binding is markedly enhanced by low and high pH values. This binding is also inhibited by sodium metabisulfite which suggests that an oxidized form of the catecholamine is the active binding species. Experiments with several group specific reagents indicate that binding may require a free sulfhydryl group but not a carboxyl function. The binding process requires an energy of activation of 14.8 kcal/mole whose magnitude may be partly explained, with the aid of optical rotatory dispersion spectra, by a non-stereoslective conformational change in protein structure induced by the amine. The characteristics of the 3H-NE binding sites observed in the microsomal fractional of the rabbit aorta appear to be different from those expected if binding were to the adrenoreceptors. A possible mechanism for catecholamine binding to free sulfhydryl groups on protein is presented.", "contents": "A kinetic analysis of a catechol-specific binding site in the microsomal fraction from the rabbit aorta. (-)-3/-Norepinephrine (3H-NE) binding to the microsomal fraction of the rabbit aorta has been studied. Binding appears to increase linearly with time up to at least 30 min, shows no evidence of stereoselectivity and may be inhibited only by compounds possessing the catechol or 3-methoxy-4hydroxyphenyl moieties, with the latter being 100-fold less effective. 3H-NE binding is saturable with a Km of 8.5 X 10(-8) M and V max of 28 pmoles/mg protein. A Hill plot indicates that binding is noncooperative whereas a Scatchard plot suggests that two sites may be present. Binding does not appear to require physiological concentrations of Ca2+ or Mg2+ and is inhibited significantly by EDTA and sodium metabisulfite. In addition, binding is markedly enhanced by low and high pH values. This binding is also inhibited by sodium metabisulfite which suggests that an oxidized form of the catecholamine is the active binding species. Experiments with several group specific reagents indicate that binding may require a free sulfhydryl group but not a carboxyl function. The binding process requires an energy of activation of 14.8 kcal/mole whose magnitude may be partly explained, with the aid of optical rotatory dispersion spectra, by a non-stereoslective conformational change in protein structure induced by the amine. The characteristics of the 3H-NE binding sites observed in the microsomal fractional of the rabbit aorta appear to be different from those expected if binding were to the adrenoreceptors. A possible mechanism for catecholamine binding to free sulfhydryl groups on protein is presented."}
{"id": "PMID:8321", "title": "Alpha-adrenergic activity of N,N-dimethyldopamine (DMDA).", "content": "The autonomic and cardiovascular activity of N,N-dimethyldopamine (DMDA) was studied in the dog and rabbit. DMDA appears to be a postganglionic sympathetic alpha-adrenoceptor agonist since it consistently caused vasconstriction in several isolated vascular beds, even in the presence of ganglionic blockade. The pressor activity of DMDA was attenuated by the alpha-adrenergic antagonist phentolamine. Calculated pA2 values for phentolamine against both DMDA and norepinephrine in isolated rabbit arteries were in close agreement. DMDA inhibits cardioaccelerator nerve stimulation induced chronotropic responses by a mechanism which appears to be alpha-adrenergic in the dog.", "contents": "Alpha-adrenergic activity of N,N-dimethyldopamine (DMDA). The autonomic and cardiovascular activity of N,N-dimethyldopamine (DMDA) was studied in the dog and rabbit. DMDA appears to be a postganglionic sympathetic alpha-adrenoceptor agonist since it consistently caused vasconstriction in several isolated vascular beds, even in the presence of ganglionic blockade. The pressor activity of DMDA was attenuated by the alpha-adrenergic antagonist phentolamine. Calculated pA2 values for phentolamine against both DMDA and norepinephrine in isolated rabbit arteries were in close agreement. DMDA inhibits cardioaccelerator nerve stimulation induced chronotropic responses by a mechanism which appears to be alpha-adrenergic in the dog."}
{"id": "PMID:8327", "title": "Glycoprotein biosynthesis in splenic cells. Purification of a microsomal galactosyl-transferase.", "content": "One part of the microsomal galactosyl-transferase activity of splenic cells of rats can by solubilized by the action of Triton X-100 and Tween 20. Its purification on a Sephadex G-200 column and by electrophoresis on a polyacrylamide gel leads to a solution of high specific enzymic activity.", "contents": "Glycoprotein biosynthesis in splenic cells. Purification of a microsomal galactosyl-transferase. One part of the microsomal galactosyl-transferase activity of splenic cells of rats can by solubilized by the action of Triton X-100 and Tween 20. Its purification on a Sephadex G-200 column and by electrophoresis on a polyacrylamide gel leads to a solution of high specific enzymic activity."}
{"id": "PMID:8329", "title": "Beta-adrenergic blocking agents as potent antagonists of mescaline-induced contractions in the rat uterus.", "content": "In the isolated rat uterus, mescaline induces contractions that are notably antagonized by catecholamines, by beta-adrenergic stimulants and certain beta-adrenergic blocking agents as well as by chlorpromazine, amitriptyline and methysergide.", "contents": "Beta-adrenergic blocking agents as potent antagonists of mescaline-induced contractions in the rat uterus. In the isolated rat uterus, mescaline induces contractions that are notably antagonized by catecholamines, by beta-adrenergic stimulants and certain beta-adrenergic blocking agents as well as by chlorpromazine, amitriptyline and methysergide."}
{"id": "PMID:8330", "title": "Influence of castration and testosterone replacement on hypothalamic tyrosine hydroxylase activity in the rat.", "content": "Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that both Vmax and Km were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH4 cofactor. TP replacement to castrate rats increased the Km for added DMPH4 cofactor, while Vmax decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzyme-reduced pteridine cofactor complex.", "contents": "Influence of castration and testosterone replacement on hypothalamic tyrosine hydroxylase activity in the rat. Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that both Vmax and Km were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH4 cofactor. TP replacement to castrate rats increased the Km for added DMPH4 cofactor, while Vmax decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzyme-reduced pteridine cofactor complex."}
{"id": "PMID:8341", "title": "Effects of autonomic drugs on epididymal contractions.", "content": "The spontaneous contractility of rat epididymis was recorded in vivo and the effects of various autonomic drugs were studied. Norepinephrine, epinephrine, and orciprenaline produced a sudden increase in tonus and in the size and frequency of epididymal contractions. Phentolamine (an alpha-blocker agent) inhibited the effects of norepinephrine. On the other hand, alprenolol (a beta-blocker agent) inhibited the effects of orciprenaline but did not block the effects of norepinephrine. In addition, phentolamine and alprenolol decreased the spontaneous activity of the epididymis. Acetylcholine produced effects similar to those of norepinephrine. These effects were blocked by atropine. The results described would indicate the presence of the two receptors, alpha and beta, and that both are mediators of stimulatory effects.", "contents": "Effects of autonomic drugs on epididymal contractions. The spontaneous contractility of rat epididymis was recorded in vivo and the effects of various autonomic drugs were studied. Norepinephrine, epinephrine, and orciprenaline produced a sudden increase in tonus and in the size and frequency of epididymal contractions. Phentolamine (an alpha-blocker agent) inhibited the effects of norepinephrine. On the other hand, alprenolol (a beta-blocker agent) inhibited the effects of orciprenaline but did not block the effects of norepinephrine. In addition, phentolamine and alprenolol decreased the spontaneous activity of the epididymis. Acetylcholine produced effects similar to those of norepinephrine. These effects were blocked by atropine. The results described would indicate the presence of the two receptors, alpha and beta, and that both are mediators of stimulatory effects."}
{"id": "PMID:8343", "title": "[Studies of various factors in thyrotropoin releasing hromone TRH) radioimmunoassay for serum (author's transl)].", "content": "To study the significance of TRH in the hypothalamo-pituitary-thyroid axis measurement of TRH in body fluid are needed. We previously reported TRH radioimmunoassay for urine. TRH radioimmunoassay for serum has not established yet, because TRH immunoreactivity is inactivated with serum. We investigated effects of various factors on this inactivation and method for prevention of this inactivation. Synthetic TRH was added to normal human serum at 4 degrees C and incubated at 60 degrees C, 37 degrees C, 20 degrees C, 4 degrees C or -20 degrees C for various intervals. After incubation, recovery of TRH was measured. After one hour incubation, recovery of TRH was 9.2% at 37 degrees C, 34.5% at 20 degrees C, 100% at 4 degrees C or -20 degrees C. Incubation of TRH serum mixtures at 65 degrees C after incubation at 37 degrees C resulted in some recovery of TRH. After one hour incubation at 37 degrees C, recovery of TRH was 9.2% at serum pH 7.0, 100% at serum pH 3.0 to 5.0 or 11.0. Recovery of TRH was increased in accordance with stepwisely increase of serum dilution. Concentrations of serum thyroid hormone did not affect recovery of TRH. Smaller quantities of TRH were more rapidly inactivated. Inactivation of TRH immunoreactivity could be prevented addition of BAL (over 0.25 mg/ml) or mixture of 8-Hydroxyquinoline (HQ) and Tween 20(T) (over 0.1 mg/ml of HQ and 1 lmg/ml of T). Duration of effectiveness of BAL was short. Effectiveness of HQT continued for 12 weeks, if HQT treated serum was stored at -20 degrees C. From above data it was suggested that TRH immunoreactivity might be inactivated with enzyme system and other factors and TRH levels in the serum might be able to measure with addition of HQT to serum.", "contents": "[Studies of various factors in thyrotropoin releasing hromone TRH) radioimmunoassay for serum (author's transl)]. To study the significance of TRH in the hypothalamo-pituitary-thyroid axis measurement of TRH in body fluid are needed. We previously reported TRH radioimmunoassay for urine. TRH radioimmunoassay for serum has not established yet, because TRH immunoreactivity is inactivated with serum. We investigated effects of various factors on this inactivation and method for prevention of this inactivation. Synthetic TRH was added to normal human serum at 4 degrees C and incubated at 60 degrees C, 37 degrees C, 20 degrees C, 4 degrees C or -20 degrees C for various intervals. After incubation, recovery of TRH was measured. After one hour incubation, recovery of TRH was 9.2% at 37 degrees C, 34.5% at 20 degrees C, 100% at 4 degrees C or -20 degrees C. Incubation of TRH serum mixtures at 65 degrees C after incubation at 37 degrees C resulted in some recovery of TRH. After one hour incubation at 37 degrees C, recovery of TRH was 9.2% at serum pH 7.0, 100% at serum pH 3.0 to 5.0 or 11.0. Recovery of TRH was increased in accordance with stepwisely increase of serum dilution. Concentrations of serum thyroid hormone did not affect recovery of TRH. Smaller quantities of TRH were more rapidly inactivated. Inactivation of TRH immunoreactivity could be prevented addition of BAL (over 0.25 mg/ml) or mixture of 8-Hydroxyquinoline (HQ) and Tween 20(T) (over 0.1 mg/ml of HQ and 1 lmg/ml of T). Duration of effectiveness of BAL was short. Effectiveness of HQT continued for 12 weeks, if HQT treated serum was stored at -20 degrees C. From above data it was suggested that TRH immunoreactivity might be inactivated with enzyme system and other factors and TRH levels in the serum might be able to measure with addition of HQT to serum."}
{"id": "PMID:8344", "title": "[Cutaneous side effects of systemic drugs. Part 4 of a synopsis. 6/7. Drugs affecting the central nervous system. C. Drug-induced photosensitivity. D. Drug-induced changes of skin color].", "content": "This, the fourth part of a synopisis of cutaneous side effects of drugs, covers the drugs affecting the central nervous system: antiepileptics, hypnotics, narcotics and psychopharmaceutics; the myorelaxants and antiallergics follow, and lastly there is a section on drug addiction and placebo. The various cutaneous side effects are listed in chart form referring to more than 500 sources. A drug index is attached for handy reference. The reviews of certain drug induced skin disorders are continued with tables covering photosensitivity and changes in skin colour. Phototoxicity, photoallergy and light sensitivity by porphyria are differentiated. The various pigmentation disorders, colour changes due to metal deposits as well as different localisations are included.", "contents": "[Cutaneous side effects of systemic drugs. Part 4 of a synopsis. 6/7. Drugs affecting the central nervous system. C. Drug-induced photosensitivity. D. Drug-induced changes of skin color]. This, the fourth part of a synopisis of cutaneous side effects of drugs, covers the drugs affecting the central nervous system: antiepileptics, hypnotics, narcotics and psychopharmaceutics; the myorelaxants and antiallergics follow, and lastly there is a section on drug addiction and placebo. The various cutaneous side effects are listed in chart form referring to more than 500 sources. A drug index is attached for handy reference. The reviews of certain drug induced skin disorders are continued with tables covering photosensitivity and changes in skin colour. Phototoxicity, photoallergy and light sensitivity by porphyria are differentiated. The various pigmentation disorders, colour changes due to metal deposits as well as different localisations are included."}
{"id": "PMID:8356", "title": "Gastric and extragastric gastrin release in normal subjects in duodenal ulcer patients, and in patients with partial gastrectomy (Billroth I).", "content": "In 10 normal subjects, in 32 patients with duodenal ulcer (DU), and in 11 patients with partial gastrectomy (Billroth I), serum gastrin rose significantly after an oral and intraduodenal test meal. The highest increases were observed in DU patients after the oral as well as after the intraduodenal test meal. After the intraduodenal test meal in 4 normal subjects and in 17 DU patients an increase of gastric acid secretion and serum gastrin was measured. In basal state, after an intraduodenal or an oral test meal, DU patients with normal gastric acid secretory capacity had higher serum gastrin concentrations than DU patients with gastric hypersecretion. There was a good correlation between peak serum gastrin levels after the oral and after the intraduodenal test meal. From these data it is concluded: (1) Intraduodenal application of a test meal results in release of gastrin from extragastric sites. (2) Extragastric gastrin is biologically active. (3) DU patients are able to release more antral and more extragastric gastrin in response to a test meal. Further studies, however, are necessary to show the significance of these findings in the pathogenesis of peptic ulcer disease.", "contents": "Gastric and extragastric gastrin release in normal subjects in duodenal ulcer patients, and in patients with partial gastrectomy (Billroth I). In 10 normal subjects, in 32 patients with duodenal ulcer (DU), and in 11 patients with partial gastrectomy (Billroth I), serum gastrin rose significantly after an oral and intraduodenal test meal. The highest increases were observed in DU patients after the oral as well as after the intraduodenal test meal. After the intraduodenal test meal in 4 normal subjects and in 17 DU patients an increase of gastric acid secretion and serum gastrin was measured. In basal state, after an intraduodenal or an oral test meal, DU patients with normal gastric acid secretory capacity had higher serum gastrin concentrations than DU patients with gastric hypersecretion. There was a good correlation between peak serum gastrin levels after the oral and after the intraduodenal test meal. From these data it is concluded: (1) Intraduodenal application of a test meal results in release of gastrin from extragastric sites. (2) Extragastric gastrin is biologically active. (3) DU patients are able to release more antral and more extragastric gastrin in response to a test meal. Further studies, however, are necessary to show the significance of these findings in the pathogenesis of peptic ulcer disease."}
{"id": "PMID:8357", "title": "Effects of carbenoxolone on gastric mucosal permeability and blood flow in the dog.", "content": "The effects of topical application of carbenoxolone at neutral and acidic pH were compared in exteriorized, chambered segments of canine gastric corpus. When dissolved in saline at pH 7.5 to 8.0, 0.25% carbenoxolone caused a rapid drop in gastric potential difference of 56 +/- 2 mv and greatly increased permeability to H+ ions. Blood flow, as measured by radioactive microspheres, was not changed by carbenoxolone treatment, but subsequent exposure to isotonic HC1 caused an abrupt rise in flow. Application of 0.25% carbenoxolone suspension in isotonic HC1 caused no change in potential difference, permeability, or blood flow. Neither carbenoxolone preparation had a significant effect on aspirin-induced H+ back-diffusion or injury.", "contents": "Effects of carbenoxolone on gastric mucosal permeability and blood flow in the dog. The effects of topical application of carbenoxolone at neutral and acidic pH were compared in exteriorized, chambered segments of canine gastric corpus. When dissolved in saline at pH 7.5 to 8.0, 0.25% carbenoxolone caused a rapid drop in gastric potential difference of 56 +/- 2 mv and greatly increased permeability to H+ ions. Blood flow, as measured by radioactive microspheres, was not changed by carbenoxolone treatment, but subsequent exposure to isotonic HC1 caused an abrupt rise in flow. Application of 0.25% carbenoxolone suspension in isotonic HC1 caused no change in potential difference, permeability, or blood flow. Neither carbenoxolone preparation had a significant effect on aspirin-induced H+ back-diffusion or injury."}
{"id": "PMID:8360", "title": "Recombinant clone heterogeneity in Escherichia coli conjunction: effect of pH and partially replicated recipient deoxyribonucleic acid.", "content": "At pH 6.8, a substantial fraction of recombinant colonies obtained from conjugation with an HfrH donor contained multiple recombinant classes in a single colony (polygenotype colony). In contrast, when the conjugation was performed at pH 7.6, the number of polygenotypic colonies was drastically reduced, and the recombinant colonies were predominantly monogenotypic or digenotypic. Genetic analysis revealed that the digenotypic recombinants differ in those donor markers near the origin of DNA replication but share those donor markers near the terminus. This integration pattern suggests that the formation of digenotypic recombinants involves recombination of a single copy of the exogenome with a partially replicated recipient DNA molecule. This suggestion was supported by examination of the genotype of recombinant colonies recovered from crosses with an HfrKL96 donor which was derived from HfrH but transfers its chromosome in the reverse direction.", "contents": "Recombinant clone heterogeneity in Escherichia coli conjunction: effect of pH and partially replicated recipient deoxyribonucleic acid. At pH 6.8, a substantial fraction of recombinant colonies obtained from conjugation with an HfrH donor contained multiple recombinant classes in a single colony (polygenotype colony). In contrast, when the conjugation was performed at pH 7.6, the number of polygenotypic colonies was drastically reduced, and the recombinant colonies were predominantly monogenotypic or digenotypic. Genetic analysis revealed that the digenotypic recombinants differ in those donor markers near the origin of DNA replication but share those donor markers near the terminus. This integration pattern suggests that the formation of digenotypic recombinants involves recombination of a single copy of the exogenome with a partially replicated recipient DNA molecule. This suggestion was supported by examination of the genotype of recombinant colonies recovered from crosses with an HfrKL96 donor which was derived from HfrH but transfers its chromosome in the reverse direction."}
{"id": "PMID:8361", "title": "[Galenic studies of a new gastrotherapeutic drug].", "content": "This paper presents the methods for galenical investigations of a new gastrotherapeutic preparation. The results and their possible relations to therapy are discussed. The preparation is presented a press-coated tablet. Its antacid characteristics concerning the rate of effectiveness, potency and duration are compared with leading brands on the German market. Pepsin inactivation together with the rapid liberation of the spasmolytic agent propantheline and the psychically stabilising agent peranzine are demonstrated. The results of the stability tests for the active ingredients and the in vitro availability are described. The new product is a gastrotherapeutic preparation, which fulfils all requirements for rapid action and reliable therapy.", "contents": "[Galenic studies of a new gastrotherapeutic drug]. This paper presents the methods for galenical investigations of a new gastrotherapeutic preparation. The results and their possible relations to therapy are discussed. The preparation is presented a press-coated tablet. Its antacid characteristics concerning the rate of effectiveness, potency and duration are compared with leading brands on the German market. Pepsin inactivation together with the rapid liberation of the spasmolytic agent propantheline and the psychically stabilising agent peranzine are demonstrated. The results of the stability tests for the active ingredients and the in vitro availability are described. The new product is a gastrotherapeutic preparation, which fulfils all requirements for rapid action and reliable therapy."}
{"id": "PMID:8362", "title": "[Field study on the decrease of lipids using etofibrate].", "content": "A field-trial on Etofibrat was performed on 4405 patients suffering from primary and secondary hyperlipoproteinemia. The results were proved statistically. After a 3 to 4 weeks treatment the concentration of cholesterol as well as tryglicerides in the serum decreased significantly. After 6 to 8 weeks treatment the lipid-lowering effect was even stronger. Nearly 90% of the patients investigated gave a positive response to the treatment. Part of the population had undergone a treatment with other lipid-lowering agents before-most likely without sufficient success-in these cases a further lipid-lowering effect due to Etofibrat could be shown. Under-dosage in premedication cannot be excluded. The stratification of the patients in different groups of diagnosis showed a nearly similarity of both blood lipids independent of the diagnosis. This could also be confirmed for the group of patients suffering from diabetes. To prove the lipid-lowering efficacy of Etofibrat a population was withdrawn from treatment. Cholesterol as well as tryglicerides increased significantly during the interval without treatment. During a long-term study both lipid fractions could be kept down without increasing of the daily Etofibrat dose. The tolerance of Etofibrat was stated to be good up to very good. Objectively the measured enzymes SGOT, SGPT and gamma-GT showed a decrease of the means. Subjectively the occurrence of an often intermediate heat sensation and/or rubedo was of relevance. The low daily dose compared with other lipid-lowering agents gives indication for a better pharmacocinetic behaviour of the drug;", "contents": "[Field study on the decrease of lipids using etofibrate]. A field-trial on Etofibrat was performed on 4405 patients suffering from primary and secondary hyperlipoproteinemia. The results were proved statistically. After a 3 to 4 weeks treatment the concentration of cholesterol as well as tryglicerides in the serum decreased significantly. After 6 to 8 weeks treatment the lipid-lowering effect was even stronger. Nearly 90% of the patients investigated gave a positive response to the treatment. Part of the population had undergone a treatment with other lipid-lowering agents before-most likely without sufficient success-in these cases a further lipid-lowering effect due to Etofibrat could be shown. Under-dosage in premedication cannot be excluded. The stratification of the patients in different groups of diagnosis showed a nearly similarity of both blood lipids independent of the diagnosis. This could also be confirmed for the group of patients suffering from diabetes. To prove the lipid-lowering efficacy of Etofibrat a population was withdrawn from treatment. Cholesterol as well as tryglicerides increased significantly during the interval without treatment. During a long-term study both lipid fractions could be kept down without increasing of the daily Etofibrat dose. The tolerance of Etofibrat was stated to be good up to very good. Objectively the measured enzymes SGOT, SGPT and gamma-GT showed a decrease of the means. Subjectively the occurrence of an often intermediate heat sensation and/or rubedo was of relevance. The low daily dose compared with other lipid-lowering agents gives indication for a better pharmacocinetic behaviour of the drug;"}
{"id": "PMID:8364", "title": "Plasma insulin concentration during physiological variations in immunoreactive plasma secretin.", "content": "The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject.", "contents": "Plasma insulin concentration during physiological variations in immunoreactive plasma secretin. The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject."}
{"id": "PMID:8366", "title": "Stability of the insoluble form of uridine kinase coupled to zn2+ or pb2+ ions.", "content": "Partially purified calf brain uridine kinase precipitated by bivalent metal cations has been compared with the soluble enzyme fraction regarding its stability in the presence of inactivating factors. The freeze-dried preparations of uridine kinase precipitaated by Pb2+ or Zn2+ ions, althouth enzymatically highly active, are insoluble in aqueous solutions. The activity of metal-insolubilized enzymes disappears during their preincubation in acidic media or in the presence of silver ions. Also trypsin, chymotrypsin and cathepsin B1 caused decreases in enzyme activity. However, fractions which have been precipitated by metal ions and freeze-dried are stable at high temperatures, whereas the activity of soluble uridine kinase is completely lost. Both unheated metal-ion precipitated uridine kinase preparations and those heated at 100 degrees C are equally sensitive to the feedback inhibition by CTP.", "contents": "Stability of the insoluble form of uridine kinase coupled to zn2+ or pb2+ ions. Partially purified calf brain uridine kinase precipitated by bivalent metal cations has been compared with the soluble enzyme fraction regarding its stability in the presence of inactivating factors. The freeze-dried preparations of uridine kinase precipitaated by Pb2+ or Zn2+ ions, althouth enzymatically highly active, are insoluble in aqueous solutions. The activity of metal-insolubilized enzymes disappears during their preincubation in acidic media or in the presence of silver ions. Also trypsin, chymotrypsin and cathepsin B1 caused decreases in enzyme activity. However, fractions which have been precipitated by metal ions and freeze-dried are stable at high temperatures, whereas the activity of soluble uridine kinase is completely lost. Both unheated metal-ion precipitated uridine kinase preparations and those heated at 100 degrees C are equally sensitive to the feedback inhibition by CTP."}
{"id": "PMID:8367", "title": "[Effect of 2-hydroxyestradiol-17beta on NADPH-dependent electron transfer in rat liver microsomes in vitro (author's transl)].", "content": "If rat liver microsomes are incubated with NADPH and 2-hydroxyestradiol-17beta in vitro, the following is observed: 1. Inhibition of lipid peroxidation, 2.inhibition of cytochrome P-450 reduction, and 3.inhibition of cytochrome b5 reduction. Beyond this the catechole inhibits lipid peroxidation of liposomes in vitro. These phenomena can be explained by interaction of different states of oxidation of the estrogen with the NADPH-cytochrome reductase and with 0-2 radicals, which leads to terminal \"uncoupling\" of microsomal electron transport.", "contents": "[Effect of 2-hydroxyestradiol-17beta on NADPH-dependent electron transfer in rat liver microsomes in vitro (author's transl)]. If rat liver microsomes are incubated with NADPH and 2-hydroxyestradiol-17beta in vitro, the following is observed: 1. Inhibition of lipid peroxidation, 2.inhibition of cytochrome P-450 reduction, and 3.inhibition of cytochrome b5 reduction. Beyond this the catechole inhibits lipid peroxidation of liposomes in vitro. These phenomena can be explained by interaction of different states of oxidation of the estrogen with the NADPH-cytochrome reductase and with 0-2 radicals, which leads to terminal \"uncoupling\" of microsomal electron transport."}
{"id": "PMID:8368", "title": "Purification and characterisation of four polypeptides with neurotoxic activity from Condylactis aurantiaca.", "content": "Four toxic polypeptides, Toxins I, II, III and IV were isolated in pure form from the sea anemone Condylactis aurantiaca (Actinaria). Toxin isolation was achieved by alcoholic extraction of the homogenised sea anemones, batchwise adsorption onto cation exchangers, gel filtration on Sephadex G-50 and G-25 and ion-exchange chromatography on SP-Sephadex and QAE-Sephadex. Toxins from Condylactis aurantiaca all contain between 49 and 51 amino acids. Their amino acid compositions were compared to those of the Anemonia sulcata toxins. The toxins were tested on the shore crab Carcinus maenas by intramusclar injection. Crabs react highly sensitively to sea anemone toxins with muscle cramps and paralysis. For Condylactis toxins LD100 ranges from 2 to 6.6 mug/kg Carcinus maenas.", "contents": "Purification and characterisation of four polypeptides with neurotoxic activity from Condylactis aurantiaca. Four toxic polypeptides, Toxins I, II, III and IV were isolated in pure form from the sea anemone Condylactis aurantiaca (Actinaria). Toxin isolation was achieved by alcoholic extraction of the homogenised sea anemones, batchwise adsorption onto cation exchangers, gel filtration on Sephadex G-50 and G-25 and ion-exchange chromatography on SP-Sephadex and QAE-Sephadex. Toxins from Condylactis aurantiaca all contain between 49 and 51 amino acids. Their amino acid compositions were compared to those of the Anemonia sulcata toxins. The toxins were tested on the shore crab Carcinus maenas by intramusclar injection. Crabs react highly sensitively to sea anemone toxins with muscle cramps and paralysis. For Condylactis toxins LD100 ranges from 2 to 6.6 mug/kg Carcinus maenas."}
{"id": "PMID:8370", "title": "Hydrolysis-resynthesis equilibrium of the lysine-15--alanine-16 peptide bond in bovine trypsin inhibitor (Kunitz).", "content": "Catalytic amounts of bovine beta-trypsin, bovine alpha-chymotrypsin and porcine plasmin establish a true thermodynamic equilibrium between virgin (I) (reactive site Lys15-Ala16 peptide bond intact) and modified (I) (this bond hydrolyzed) bovine trypsin/kallikrein inhibitor (Kunitz). The very slow reaction rates for attaining equilibrium are pH-dependent and differ for different enzymes. Optimal rates are for beta-trypsin at pH 3.75, for alpha-chymotrypsin at pH 5.5, and for plasmin at pH 5.0. Under conditions of optimum pH the equilibrium is reached with the highest rate by plasmin. In 10(-5)M inhibitor solutions the equilibrium concentrations of virgin and modified inhibitor are established by plasmin after almost 300 days starting from either pure virgin or pure modified inhibitor. Thus, the hydrolysis constant KHyd = [I]/[I] is determined to be 0.33 at pH 5.0. In spite of many unsuccessful attempts, this demonstrates that the reactive site peptide bond Lys15-Ala16 in the bovine trypsin inhibitor (Kunitz) can be hydrolyzed by catalytic amounts of endopeptidase. It further confirms that the hydrolyzed Lys15-Ala16 peptide bond in modified inhibitor is subject to thermodynamic control resynthesis.", "contents": "Hydrolysis-resynthesis equilibrium of the lysine-15--alanine-16 peptide bond in bovine trypsin inhibitor (Kunitz). Catalytic amounts of bovine beta-trypsin, bovine alpha-chymotrypsin and porcine plasmin establish a true thermodynamic equilibrium between virgin (I) (reactive site Lys15-Ala16 peptide bond intact) and modified (I) (this bond hydrolyzed) bovine trypsin/kallikrein inhibitor (Kunitz). The very slow reaction rates for attaining equilibrium are pH-dependent and differ for different enzymes. Optimal rates are for beta-trypsin at pH 3.75, for alpha-chymotrypsin at pH 5.5, and for plasmin at pH 5.0. Under conditions of optimum pH the equilibrium is reached with the highest rate by plasmin. In 10(-5)M inhibitor solutions the equilibrium concentrations of virgin and modified inhibitor are established by plasmin after almost 300 days starting from either pure virgin or pure modified inhibitor. Thus, the hydrolysis constant KHyd = [I]/[I] is determined to be 0.33 at pH 5.0. In spite of many unsuccessful attempts, this demonstrates that the reactive site peptide bond Lys15-Ala16 in the bovine trypsin inhibitor (Kunitz) can be hydrolyzed by catalytic amounts of endopeptidase. It further confirms that the hydrolyzed Lys15-Ala16 peptide bond in modified inhibitor is subject to thermodynamic control resynthesis."}
{"id": "PMID:8378", "title": "Biological effects of Escherichia coli lipopolysaccharide (LPS) in vivo. I. Selection in the mouse thymus of killer and helper cells.", "content": "In the present study we have investigated the biological effects on thymus lymphocytes resulting from Escherichia coli lipopolysaccharide (LPS) treatment in young adult mice. It has been established that LPS induces the following effects: (a) a dose-dependent reduction of thymus weight contemporaneous with a rise in the anti-LPS antibody response; (b) an increase of killer activity of thymus cells; (c) an enhancement of thymocytes helper activity; (d) a reduction of theta-positive cells in the thymus; (e) a cellular depletion in the thymus cortex. These data, indicating that LPS selects in the thymus a population of cells more efficient in expressing both killer and helper functions, are interpreted as caused by an increased rate of cortisol secretion induced by the LPS treatment.", "contents": "Biological effects of Escherichia coli lipopolysaccharide (LPS) in vivo. I. Selection in the mouse thymus of killer and helper cells. In the present study we have investigated the biological effects on thymus lymphocytes resulting from Escherichia coli lipopolysaccharide (LPS) treatment in young adult mice. It has been established that LPS induces the following effects: (a) a dose-dependent reduction of thymus weight contemporaneous with a rise in the anti-LPS antibody response; (b) an increase of killer activity of thymus cells; (c) an enhancement of thymocytes helper activity; (d) a reduction of theta-positive cells in the thymus; (e) a cellular depletion in the thymus cortex. These data, indicating that LPS selects in the thymus a population of cells more efficient in expressing both killer and helper functions, are interpreted as caused by an increased rate of cortisol secretion induced by the LPS treatment."}
{"id": "PMID:8381", "title": "Fertility control with sub-dermal silastic capsules containing a new progestin (ST-1435).", "content": "The contraceptive action of silastic implants containing a new progestion ST-1435 was investigated in 285 women of reproductive age. A group of 52 women (group A) received three capsules containing each 35 mg of the steroid. A second group of 48 women (group B) received four capsules and a third and larger group of 185 women (group C) received five capsules. No pregnancies occurred during 530 months of use in group A. In 502 months of use recorded for group B, one pregnancy occurred. In group C, 2.142 months were recorded. One pregnancy was reported at the end of 11 months of use and another at the end of 19 months of use. Alterations in the pattern of menstrual bleeding was the most common side effect.", "contents": "Fertility control with sub-dermal silastic capsules containing a new progestin (ST-1435). The contraceptive action of silastic implants containing a new progestion ST-1435 was investigated in 285 women of reproductive age. A group of 52 women (group A) received three capsules containing each 35 mg of the steroid. A second group of 48 women (group B) received four capsules and a third and larger group of 185 women (group C) received five capsules. No pregnancies occurred during 530 months of use in group A. In 502 months of use recorded for group B, one pregnancy occurred. In group C, 2.142 months were recorded. One pregnancy was reported at the end of 11 months of use and another at the end of 19 months of use. Alterations in the pattern of menstrual bleeding was the most common side effect."}
{"id": "PMID:8382", "title": "Human semen ribonuclease. Location, properties and inhibition by sodium dodecyl sulfate, zinc sulfate and EDTA.", "content": "Optimal conditions were established for RNase activity measurement. The enzyme was measured in human seminal plasma as well as in spermatozoa. Results suggest that sperm enzyme may come from seminal plasma contamination and that RNase may be used as a marker enzyme for seminal plasma contamination. Sodium dodecylsulfate, a reagent utilized to produce the solubilization of the spermatozoa, produced a very strong inhibition of the RNase at low concentrations (530 muM). Zinc sulfate and EDTA also produced inhibition of the RNase activity. Such inhibition may be very useful in future studies of RNA metabolism in human spermatozoa.", "contents": "Human semen ribonuclease. Location, properties and inhibition by sodium dodecyl sulfate, zinc sulfate and EDTA. Optimal conditions were established for RNase activity measurement. The enzyme was measured in human seminal plasma as well as in spermatozoa. Results suggest that sperm enzyme may come from seminal plasma contamination and that RNase may be used as a marker enzyme for seminal plasma contamination. Sodium dodecylsulfate, a reagent utilized to produce the solubilization of the spermatozoa, produced a very strong inhibition of the RNase at low concentrations (530 muM). Zinc sulfate and EDTA also produced inhibition of the RNase activity. Such inhibition may be very useful in future studies of RNA metabolism in human spermatozoa."}
{"id": "PMID:8383", "title": "Lack of effects of testosterone on norepinephrine turnover and tyrosine hydroxylase activity of the rat vas deferens and epididymis.", "content": "To test the effects of testosterone on some aspects of the metabolism of norepinephrine (NE) in short adrenergic neurons of the male genital tract, orchiectomized rats received 500 mug of testosterone propionate twice daily for up to 18 days. Androgen treatment did not affect the levels, uptake or efflux of NE nor modified the activity of tyrosine hydroxylase in the vas deferens and epididymis. Likewise, formaline-induced fluorescence and ultrastructure of nerve endings remained unchanged after testosterone administration. These data suggest that short adrenergic neurons of male genital tract are relatively insensitive to androgens.", "contents": "Lack of effects of testosterone on norepinephrine turnover and tyrosine hydroxylase activity of the rat vas deferens and epididymis. To test the effects of testosterone on some aspects of the metabolism of norepinephrine (NE) in short adrenergic neurons of the male genital tract, orchiectomized rats received 500 mug of testosterone propionate twice daily for up to 18 days. Androgen treatment did not affect the levels, uptake or efflux of NE nor modified the activity of tyrosine hydroxylase in the vas deferens and epididymis. Likewise, formaline-induced fluorescence and ultrastructure of nerve endings remained unchanged after testosterone administration. These data suggest that short adrenergic neurons of male genital tract are relatively insensitive to androgens."}
{"id": "PMID:8384", "title": "Fifteen years experience with artificial insemination.", "content": "Artificial insemination is today an accepted procedure in circumventing sterility. In recent years this procedure gained much popularity as the number of infants available for adoption steadily decreased due to the liberal abortion laws. A review of 15 years of practiced experience (senior author) is presented. In all described cases (168 women) artificial insemination was performed personally by the author. The high rate of success (80% of the presented cases) is attributed to a very meticulous and highly individualized approach to each case. Review of literature is presented.", "contents": "Fifteen years experience with artificial insemination. Artificial insemination is today an accepted procedure in circumventing sterility. In recent years this procedure gained much popularity as the number of infants available for adoption steadily decreased due to the liberal abortion laws. A review of 15 years of practiced experience (senior author) is presented. In all described cases (168 women) artificial insemination was performed personally by the author. The high rate of success (80% of the presented cases) is attributed to a very meticulous and highly individualized approach to each case. Review of literature is presented."}
{"id": "PMID:8385", "title": "Reversible anti-fertility effect by non-occluding oviductal copper coils in the rabbit.", "content": "Placement of two 1 cm copper (Cu) coils around the mid-region of each oviduct in a group of five female rabbits with proven fertility, 34 days before mating, virtually prevented fetal implantation in these animals. The oviducts remained patent during a 47 day implantation period and following removal of the Cu coils, does that were remated became pregnant. In two of these does an implantation rate (living fetuses/corpora lutea) of 33% (7/21) was observed and one post-Cu implanted doe had a litter of two. Among four does bearing a single Cu coil on their left oviduct for 28 days prior to mating there was 19% (4/21) implantation of the left side and 56.3% (9/16) on the untreated right side, suggesting a local action by the metal. The results indicate that Cu is an effective anti-fertility agent when implanted around the oviducts and, as a corollary, it is apparent that the metal is not restricted to placement in the uterus in order to prevent pregnancy in rabbits. Non-occluding Cu containing devices may offer a new approach to reversible fertility control in the female that merits further investigation.", "contents": "Reversible anti-fertility effect by non-occluding oviductal copper coils in the rabbit. Placement of two 1 cm copper (Cu) coils around the mid-region of each oviduct in a group of five female rabbits with proven fertility, 34 days before mating, virtually prevented fetal implantation in these animals. The oviducts remained patent during a 47 day implantation period and following removal of the Cu coils, does that were remated became pregnant. In two of these does an implantation rate (living fetuses/corpora lutea) of 33% (7/21) was observed and one post-Cu implanted doe had a litter of two. Among four does bearing a single Cu coil on their left oviduct for 28 days prior to mating there was 19% (4/21) implantation of the left side and 56.3% (9/16) on the untreated right side, suggesting a local action by the metal. The results indicate that Cu is an effective anti-fertility agent when implanted around the oviducts and, as a corollary, it is apparent that the metal is not restricted to placement in the uterus in order to prevent pregnancy in rabbits. Non-occluding Cu containing devices may offer a new approach to reversible fertility control in the female that merits further investigation."}
{"id": "PMID:8386", "title": "The effect of exogenous gondadotropins on the pre-implantation period in the rat.", "content": "It is well established that the egg implantation in the rat is dependent on a surge of gonadotropin secretion on day 4 of pregnancy. The present experiments were designed in order to demonstrate the possible effect of exogenous administration of gonadotropins during pre-implantation period in pseudopregnant rats, made pregnant after egg transfer. Groups of pseudopregnant rats by sterile mating were injected with different doses of LH and FSH, between 9:00-12:00 A.M. on day 4 of pseudopregnancy; blastocysts were transferred to them in the morning of day 6, instead of day 5. The implantation rate and the number of young born at term were the criteria of the successful extension of the sensitive period of the endometrium by the exogenous gonadotropins. From the results obtained it can be concluded that LH alone acts on the uterine sensitivity by extension of the implantation period.", "contents": "The effect of exogenous gondadotropins on the pre-implantation period in the rat. It is well established that the egg implantation in the rat is dependent on a surge of gonadotropin secretion on day 4 of pregnancy. The present experiments were designed in order to demonstrate the possible effect of exogenous administration of gonadotropins during pre-implantation period in pseudopregnant rats, made pregnant after egg transfer. Groups of pseudopregnant rats by sterile mating were injected with different doses of LH and FSH, between 9:00-12:00 A.M. on day 4 of pseudopregnancy; blastocysts were transferred to them in the morning of day 6, instead of day 5. The implantation rate and the number of young born at term were the criteria of the successful extension of the sensitive period of the endometrium by the exogenous gonadotropins. From the results obtained it can be concluded that LH alone acts on the uterine sensitivity by extension of the implantation period."}
{"id": "PMID:8387", "title": "Case report: sterility due to sperm autoagglutination.", "content": "Autoagglutination in seminal fluid of husbands in three unexplained sterile couples was found in routine semen-analysis. Further exploration showed that sera and seminal fluid of these husbands agglutinate donors' sperm, while their wives' sera did not. Post-coital tests were not significant. After failure of conservative treatment with vitamin C, two couples agreed to AID followed promptly by pregnancies and deliveries. The possible connection between sterility and sperm-auto-agglutination is discussed, stressing the justification for looking at these phenomena more carefully and with more attention.", "contents": "Case report: sterility due to sperm autoagglutination. Autoagglutination in seminal fluid of husbands in three unexplained sterile couples was found in routine semen-analysis. Further exploration showed that sera and seminal fluid of these husbands agglutinate donors' sperm, while their wives' sera did not. Post-coital tests were not significant. After failure of conservative treatment with vitamin C, two couples agreed to AID followed promptly by pregnancies and deliveries. The possible connection between sterility and sperm-auto-agglutination is discussed, stressing the justification for looking at these phenomena more carefully and with more attention."}
{"id": "PMID:8388", "title": "Distribution and removal of the acrosin of bull spermatozoa.", "content": "The effects of Hyamine 2389, Triton X-100, Nadeoxycholate, acetic acid and hypertonic KCl and MgCl2 as well as freezing and thawing and sonication were studied on the solubilization of acrosin from washed bull spermatozoa, from Hyamine-pretreated spermatozoa (devoid of cell and outer acrosome membrane and of acrosomal material) and from isolated acrosomal caps and vesicles. Concurrent ultrastructural changes were observed. Hyamine, Triton, KCl, and acetic acid effectively solubilized acrosin from whole spermatozoa but MgCl2 had a poor effect. The outer acrosome membrane and acrosomal material extracted by Hyamine contained about 35-40% of the total acrosin activity, and three quarters of it was soluble. The rest of acrosin situated in the innter acrosome membrane or equatorial segment was best extracted by hypertonic KCl and MgCl2, but the detergents were ineffective in this case indicating that acrosin is bound differently to the outer and inner parts of acrosome. The opposite effect of MgCl2 on the acrosin activities extracted from these two parts could even be a suggestion of multiple forms of acrosin. The increase of the total acrosin activity during the Hyamine treatment indicates that acrosin is partly in an inactive form. due either to steric hindrance, inhibitor complex of existence of a proacrosin.", "contents": "Distribution and removal of the acrosin of bull spermatozoa. The effects of Hyamine 2389, Triton X-100, Nadeoxycholate, acetic acid and hypertonic KCl and MgCl2 as well as freezing and thawing and sonication were studied on the solubilization of acrosin from washed bull spermatozoa, from Hyamine-pretreated spermatozoa (devoid of cell and outer acrosome membrane and of acrosomal material) and from isolated acrosomal caps and vesicles. Concurrent ultrastructural changes were observed. Hyamine, Triton, KCl, and acetic acid effectively solubilized acrosin from whole spermatozoa but MgCl2 had a poor effect. The outer acrosome membrane and acrosomal material extracted by Hyamine contained about 35-40% of the total acrosin activity, and three quarters of it was soluble. The rest of acrosin situated in the innter acrosome membrane or equatorial segment was best extracted by hypertonic KCl and MgCl2, but the detergents were ineffective in this case indicating that acrosin is bound differently to the outer and inner parts of acrosome. The opposite effect of MgCl2 on the acrosin activities extracted from these two parts could even be a suggestion of multiple forms of acrosin. The increase of the total acrosin activity during the Hyamine treatment indicates that acrosin is partly in an inactive form. due either to steric hindrance, inhibitor complex of existence of a proacrosin."}
{"id": "PMID:8389", "title": "The effect of prostaglandins F1 alpha and F2 alpha on spermatogenesis.", "content": "The effect of the prostaglandins F1 alpha and F2 alpha on spermatogenesis in the mature male mouse has been studied. Administration of prostaglandins F1 alpha and F2 alpha subcutaneously at a dose of 3 mg/kg once a day for 15 days produced a pronounced decrease in spermatogenesis primarily during the meiotic phase as reflected by a significant decrease in stage 7 spermatids as compared to controls. PGF2 alpha produced a stronger suppression than did PGF1 alpha. Accessory reproductive gland weights also appeared to be reduced by the prostaglandins, although not consistently. Histopathological examination revealed increased numbers of exfoliated immature germinal cells in the seminiferous tubules and epididymi of prostaglandin treated animals. When the effect of PGF1 alpha and PGF2 alpha were compared to those of PGE1 and PGE2 it was found that PGE2 produced the strongest suppression, with PGF2 alpha, PGE1 and PGF1 following in decreasing order respectively.", "contents": "The effect of prostaglandins F1 alpha and F2 alpha on spermatogenesis. The effect of the prostaglandins F1 alpha and F2 alpha on spermatogenesis in the mature male mouse has been studied. Administration of prostaglandins F1 alpha and F2 alpha subcutaneously at a dose of 3 mg/kg once a day for 15 days produced a pronounced decrease in spermatogenesis primarily during the meiotic phase as reflected by a significant decrease in stage 7 spermatids as compared to controls. PGF2 alpha produced a stronger suppression than did PGF1 alpha. Accessory reproductive gland weights also appeared to be reduced by the prostaglandins, although not consistently. Histopathological examination revealed increased numbers of exfoliated immature germinal cells in the seminiferous tubules and epididymi of prostaglandin treated animals. When the effect of PGF1 alpha and PGF2 alpha were compared to those of PGE1 and PGE2 it was found that PGE2 produced the strongest suppression, with PGF2 alpha, PGE1 and PGF1 following in decreasing order respectively."}
{"id": "PMID:8390", "title": "Immunological factors and post coital test in unexplained infertility.", "content": "Twenty-four couples facing longstanding primary or secondary infertility underwent semen analysis, PCT, functional evaluation of menstrual cycle, hysterosalpingography and laparscopy. All clinical findings were normal with the exception of PCT which was positive in 13 and negative in 11. All the women underwent a multiple approach investigation of local and circulating antibodies production as well as cell-mediated immunity against live spermatozoa. Sperm Immobilization Test (SIT) and Spermatotoxicity Tests (STT) were performed in a single experimental design on cervical mucus and blood serum. Leucocyte Migration Inhibition Test in presence of sperms (LMIT) was done on peripheral leucocytes. Local antispermatic activity in the cervical mucus was negative in all PCT positive cases, and positive in six out of 11 PCT negative cases. SIT and STT were both positive in cervical mucus and in blood in one case only. No correlation could be found between PCT and serum SIT, STT or LMIT. The fertility pattern expressed by the number of pregnancies per years of exposure, already low in the whole group, was even lower in the sub-groups with positive immunological factors. Positive immunological factors do not exclude the possibility of conception but appear to be associated with a reduced rate of conception.", "contents": "Immunological factors and post coital test in unexplained infertility. Twenty-four couples facing longstanding primary or secondary infertility underwent semen analysis, PCT, functional evaluation of menstrual cycle, hysterosalpingography and laparscopy. All clinical findings were normal with the exception of PCT which was positive in 13 and negative in 11. All the women underwent a multiple approach investigation of local and circulating antibodies production as well as cell-mediated immunity against live spermatozoa. Sperm Immobilization Test (SIT) and Spermatotoxicity Tests (STT) were performed in a single experimental design on cervical mucus and blood serum. Leucocyte Migration Inhibition Test in presence of sperms (LMIT) was done on peripheral leucocytes. Local antispermatic activity in the cervical mucus was negative in all PCT positive cases, and positive in six out of 11 PCT negative cases. SIT and STT were both positive in cervical mucus and in blood in one case only. No correlation could be found between PCT and serum SIT, STT or LMIT. The fertility pattern expressed by the number of pregnancies per years of exposure, already low in the whole group, was even lower in the sub-groups with positive immunological factors. Positive immunological factors do not exclude the possibility of conception but appear to be associated with a reduced rate of conception."}
{"id": "PMID:8391", "title": "Pituitary and testicular response to hypothalamic LH-releasing hormone (LH-RH) in normal and oligospermic men.", "content": "A comparative study was done of the basal and post-LH-RH stimulation levels of LH, FSH and Testosterone (T) in 10 healthy, male volunteers, aged 24-35 years, and in 25 normogonadotropic oligospermic men aged 23-43 years in whom other endocrine, urologic and/or vascular diseases had been rules out. Seventeen of the latter group underwent bilateral testicular biopsy. Each subject received rapid i.v. injection of 50 mug synthetic LH-RH at 8:00 A.M. Serum levels of LH, FSH and T were determined by radioimmunoassay on samples obtained immediately before and 30 and 45 minutes after injection. As compared to normals, oligospermic men had a lower average LH response, although the basal values did not differ significantly from normal. FSH levels did not differ significantly between groups, although some individual patients showed higher and some lower than normal values. The possibility of stimulating T secretion with LH-RH was confirmed. Average serum T levels rose more slowly and reached lower levels in the oligospermic men than in normal men. There was no correlation between LH and FSH rises. It is postulated that some patients with normogonadotropic oligospermia may have latent insufficiency of pituitary gonadotropic functional reserve for one or both hormones and/or of the Leydig cell function. The need for individual analysis of results and their correlation with testicular biopsy findings is commented.", "contents": "Pituitary and testicular response to hypothalamic LH-releasing hormone (LH-RH) in normal and oligospermic men. A comparative study was done of the basal and post-LH-RH stimulation levels of LH, FSH and Testosterone (T) in 10 healthy, male volunteers, aged 24-35 years, and in 25 normogonadotropic oligospermic men aged 23-43 years in whom other endocrine, urologic and/or vascular diseases had been rules out. Seventeen of the latter group underwent bilateral testicular biopsy. Each subject received rapid i.v. injection of 50 mug synthetic LH-RH at 8:00 A.M. Serum levels of LH, FSH and T were determined by radioimmunoassay on samples obtained immediately before and 30 and 45 minutes after injection. As compared to normals, oligospermic men had a lower average LH response, although the basal values did not differ significantly from normal. FSH levels did not differ significantly between groups, although some individual patients showed higher and some lower than normal values. The possibility of stimulating T secretion with LH-RH was confirmed. Average serum T levels rose more slowly and reached lower levels in the oligospermic men than in normal men. There was no correlation between LH and FSH rises. It is postulated that some patients with normogonadotropic oligospermia may have latent insufficiency of pituitary gonadotropic functional reserve for one or both hormones and/or of the Leydig cell function. The need for individual analysis of results and their correlation with testicular biopsy findings is commented."}
{"id": "PMID:8394", "title": "Alkaline phosphatase, arylsulfatase and beta-glucuronidase in saliva of cyclic women.", "content": "Levels of the enzymes alkaline phosphatase, arylsulfatase, and beta-glucuronidase have been measured in whole unstimulated saliva samples collected daily during normal menstrual cycles. The cellular content of the saliva has been shown to be a major source of the three enzymes. The enzymes were found to have peak maximum levels of activity during the periovulatory -hase of the cycle. This observation can be attributed to the presence of increased numbers of exfoliated cells from the oral mucosa resulting from the pre-ovulatory estrogen stimulus to cell proliferation.", "contents": "Alkaline phosphatase, arylsulfatase and beta-glucuronidase in saliva of cyclic women. Levels of the enzymes alkaline phosphatase, arylsulfatase, and beta-glucuronidase have been measured in whole unstimulated saliva samples collected daily during normal menstrual cycles. The cellular content of the saliva has been shown to be a major source of the three enzymes. The enzymes were found to have peak maximum levels of activity during the periovulatory -hase of the cycle. This observation can be attributed to the presence of increased numbers of exfoliated cells from the oral mucosa resulting from the pre-ovulatory estrogen stimulus to cell proliferation."}
{"id": "PMID:8395", "title": "A new model for antisperm autoimmunity in guine pigs.", "content": "Adult outbread male guinea pigs were autoimmunized without adjuvant. Homogenates were prepared with one of their own testes previously submitted \"in vivo\" and \"in vitro\" to thermal injury. Animals received a single or daily repeated intradermal injection without added adjuvant, in one or different skin sites. Guinea pigs daily sensitized in the same site during 30 days showed the presence of: a) dermal granuloma at the site of injection; b) several foci of typical allergic orchitis; c) delayed hypersensitivity detected by inhibition of macrophage migration; d) moderate titres of spermagglutinins and negligible levels of hemagglutinating antibodies. Guinea pigs receiving a single dose in one site only developed delayed hypersensitivity. Animals daily sensitized with the same dose of altered antigen in different sites, or with normal testis antigen either in one or different sites, showed negative results. The correlation among testicular lesion, dermal granuloma and cellular immunity is discussed. It is concluded that testis autosensitization is obtained in the absence of added adjuvant provided that a thermally injured gonad used as antigen is repeatedly injected in the same site.", "contents": "A new model for antisperm autoimmunity in guine pigs. Adult outbread male guinea pigs were autoimmunized without adjuvant. Homogenates were prepared with one of their own testes previously submitted \"in vivo\" and \"in vitro\" to thermal injury. Animals received a single or daily repeated intradermal injection without added adjuvant, in one or different skin sites. Guinea pigs daily sensitized in the same site during 30 days showed the presence of: a) dermal granuloma at the site of injection; b) several foci of typical allergic orchitis; c) delayed hypersensitivity detected by inhibition of macrophage migration; d) moderate titres of spermagglutinins and negligible levels of hemagglutinating antibodies. Guinea pigs receiving a single dose in one site only developed delayed hypersensitivity. Animals daily sensitized with the same dose of altered antigen in different sites, or with normal testis antigen either in one or different sites, showed negative results. The correlation among testicular lesion, dermal granuloma and cellular immunity is discussed. It is concluded that testis autosensitization is obtained in the absence of added adjuvant provided that a thermally injured gonad used as antigen is repeatedly injected in the same site."}
{"id": "PMID:8397", "title": "Quantitative study of spermatogenesis in vasectomized mice.", "content": "Adult mice were vasectomized under semi-sterile conditions and examined five weeks later. The weight of the epididymis was increased but none of the animals had developed spermatic granulomas. The concentration of testosterone in the plasma, the body weight and the weight of the testes were not affected by vasectomy. Cross sections of the testes were prepared for histological examination and the nuclei of the various types of germinal cells were enumerated at stage VII of spermatogenesis. Vasectomy caused a small, but statistically significant, decrease in the number of preleptotene spermatocytes, pachytene spermatocytes and step 7 spermatids.", "contents": "Quantitative study of spermatogenesis in vasectomized mice. Adult mice were vasectomized under semi-sterile conditions and examined five weeks later. The weight of the epididymis was increased but none of the animals had developed spermatic granulomas. The concentration of testosterone in the plasma, the body weight and the weight of the testes were not affected by vasectomy. Cross sections of the testes were prepared for histological examination and the nuclei of the various types of germinal cells were enumerated at stage VII of spermatogenesis. Vasectomy caused a small, but statistically significant, decrease in the number of preleptotene spermatocytes, pachytene spermatocytes and step 7 spermatids."}
{"id": "PMID:8398", "title": "Fertility patterns in female mice following treatment with arginine vastocin or melatonin.", "content": "Daily injections of either 2 mug arginine vasotocin (AVT) or 100 mug melatonin significantly prolonged the estrous cycles of mature female mice. If administered daily throughout pregnancy, none of the AVT-treated mice delivered viable pups.", "contents": "Fertility patterns in female mice following treatment with arginine vastocin or melatonin. Daily injections of either 2 mug arginine vasotocin (AVT) or 100 mug melatonin significantly prolonged the estrous cycles of mature female mice. If administered daily throughout pregnancy, none of the AVT-treated mice delivered viable pups."}
{"id": "PMID:8399", "title": "The pH dependence of binding of alpha,alpha'-dibromo-p-xylenesulfonic acid to lysozyme.", "content": "The chemical modification of lysozyme (I) has been accomplished with alpha, alpha'-dibromo-p-xylenesulfonic acid (DBX) at five different pH values. I was alkylated by DBX at room temperature (28 degrees C) with decrease in enzyme activity. The rate of inactivation depended upon the pH at which alkylation was carried out. The highest rate was seen at alkaline pH values; the lowest at more acidic pH values. Amino acid analyses showed that-two lysines and two tryptophan residues had been modified at pH 9; two lysines, one tryptophan and one methionine had reacted at pH 8. A histidine residue was bound at pH 6.5 together with a tryptophan residue. At the lower pH values (2.7, 4.5, 6.5), alkylation occurred with a single tryptophan residue each. Fluorescence and CD data both ruled out the participation of tryptophans 62 or 108. Labeling experiments showed that two residues  of DBX-35S were bound per molecule of I at both pH9 and pH8; one residue of DBX was bound per molecule of I at the other pH values. Sedimentation coefficients were characteristic of native lysozyme. The stoichiometry of binding and residue modification indicated that intra-molecular cross links were established. The pH dependence of the cross-linking provides means to measure several allowed intra-molecular distances. The results presented here are consistent with the existence of side chain motion in lysozyme.", "contents": "The pH dependence of binding of alpha,alpha'-dibromo-p-xylenesulfonic acid to lysozyme. The chemical modification of lysozyme (I) has been accomplished with alpha, alpha'-dibromo-p-xylenesulfonic acid (DBX) at five different pH values. I was alkylated by DBX at room temperature (28 degrees C) with decrease in enzyme activity. The rate of inactivation depended upon the pH at which alkylation was carried out. The highest rate was seen at alkaline pH values; the lowest at more acidic pH values. Amino acid analyses showed that-two lysines and two tryptophan residues had been modified at pH 9; two lysines, one tryptophan and one methionine had reacted at pH 8. A histidine residue was bound at pH 6.5 together with a tryptophan residue. At the lower pH values (2.7, 4.5, 6.5), alkylation occurred with a single tryptophan residue each. Fluorescence and CD data both ruled out the participation of tryptophans 62 or 108. Labeling experiments showed that two residues  of DBX-35S were bound per molecule of I at both pH9 and pH8; one residue of DBX was bound per molecule of I at the other pH values. Sedimentation coefficients were characteristic of native lysozyme. The stoichiometry of binding and residue modification indicated that intra-molecular cross links were established. The pH dependence of the cross-linking provides means to measure several allowed intra-molecular distances. The results presented here are consistent with the existence of side chain motion in lysozyme."}
{"id": "PMID:8400", "title": "Complete enzymic digestion of acidic proteins.", "content": "Acidic proteins are usually resistant to complete enzymic hydrolysis. The increasing number of \"unusual\" amino acids, which are unstable to acid hydrolysis, makes it necessary to have a method of enzymic hydrolysis applicable to all proteins. The complete hydrolysis of four acidic proteins by subtilisin plus leucine amino-peptidase plus prolidase followed by carboxypeptidase C, is described. Recoveries of amino acids were in excellent agreement with the expected content from the known sequences.", "contents": "Complete enzymic digestion of acidic proteins. Acidic proteins are usually resistant to complete enzymic hydrolysis. The increasing number of \"unusual\" amino acids, which are unstable to acid hydrolysis, makes it necessary to have a method of enzymic hydrolysis applicable to all proteins. The complete hydrolysis of four acidic proteins by subtilisin plus leucine amino-peptidase plus prolidase followed by carboxypeptidase C, is described. Recoveries of amino acids were in excellent agreement with the expected content from the known sequences."}
{"id": "PMID:8401", "title": "Interpretation and applications of thermal difference spectra of proteins.", "content": "The technique of thermal perturbation difference spectroscopy for examining chromophores in proteins has been set on a more acceptable theoretical and experimental foundation. (i) The origins of the thermal effect have been analysed to explain changes in spectral band width and wavelength for simple chromophores in various solvents. Comparison with theoretical curves shows that the effect of heating chromophore solutions is mainly spectral broadening coupled with an almost negligible blue shift. The apparently anomalous behavior of tryptophan and tyrosine in aqueous solvents, where the main effect is a red shift on heating, is traced to hydrogen bonding with water. A model in which tyrosine acts simultaneously as H-donor (Type I) and H-acceptor (Type II) and the later is the more temperature sensitive, is successful in explaining all available data for a variety of solute derivatives and solvents. (ii) The contribution of chromophores in the protein interior has been assessed using polyvinyl alcohol films of differing water content. There models simulate the rigidity and low thermal expansivity of the protein interior and confirm that buried chromophores contribute negligibly if at all to thermal difference spectra. (iii) Curve-fitting procedures have been used for matching protein difference spectra over a wavelength range, to those for mixtures of models, rather than relying as hitherto on data measured at extrema.", "contents": "Interpretation and applications of thermal difference spectra of proteins. The technique of thermal perturbation difference spectroscopy for examining chromophores in proteins has been set on a more acceptable theoretical and experimental foundation. (i) The origins of the thermal effect have been analysed to explain changes in spectral band width and wavelength for simple chromophores in various solvents. Comparison with theoretical curves shows that the effect of heating chromophore solutions is mainly spectral broadening coupled with an almost negligible blue shift. The apparently anomalous behavior of tryptophan and tyrosine in aqueous solvents, where the main effect is a red shift on heating, is traced to hydrogen bonding with water. A model in which tyrosine acts simultaneously as H-donor (Type I) and H-acceptor (Type II) and the later is the more temperature sensitive, is successful in explaining all available data for a variety of solute derivatives and solvents. (ii) The contribution of chromophores in the protein interior has been assessed using polyvinyl alcohol films of differing water content. There models simulate the rigidity and low thermal expansivity of the protein interior and confirm that buried chromophores contribute negligibly if at all to thermal difference spectra. (iii) Curve-fitting procedures have been used for matching protein difference spectra over a wavelength range, to those for mixtures of models, rather than relying as hitherto on data measured at extrema."}
{"id": "PMID:8404", "title": "Studies on the acute toxicity of ionic and non-ionic contrast media following rapid intravenous injection. An experimental study in mice.", "content": "The influence of the injection rate on the acute intravenous toxicity (LD50) on mice of the ionic high osmotic contrast medium Isopaque Coronar (370 mg I/ml) and the non-ionic low osmotic Amipaque (370 mg I/ml) was investigated. At slow injection (0.1 ml/sec). Amipaque had a significantly higher LD50 than Isopaque Coronar (17.3 respectively 9.8 gm I/kg). Also at rapid injection (2 ml/10 sec). Amipaque was significantly less toxic than Isopaque Coronar (13.4 respectively 6.1 g I/kg). Thus Isopaque Coronar increased approximately 60% in toxicity while Amipaque increased 28% when the rate of injection was increased. This difference was statistically significant (p less than 0.001). Several possible mechanisms that might explain this difference, with special interest in the disturbances on the pulmonary circulation following contrast media injection, are discussed.", "contents": "Studies on the acute toxicity of ionic and non-ionic contrast media following rapid intravenous injection. An experimental study in mice. The influence of the injection rate on the acute intravenous toxicity (LD50) on mice of the ionic high osmotic contrast medium Isopaque Coronar (370 mg I/ml) and the non-ionic low osmotic Amipaque (370 mg I/ml) was investigated. At slow injection (0.1 ml/sec). Amipaque had a significantly higher LD50 than Isopaque Coronar (17.3 respectively 9.8 gm I/kg). Also at rapid injection (2 ml/10 sec). Amipaque was significantly less toxic than Isopaque Coronar (13.4 respectively 6.1 g I/kg). Thus Isopaque Coronar increased approximately 60% in toxicity while Amipaque increased 28% when the rate of injection was increased. This difference was statistically significant (p less than 0.001). Several possible mechanisms that might explain this difference, with special interest in the disturbances on the pulmonary circulation following contrast media injection, are discussed."}
{"id": "PMID:8405", "title": "Partial purification of pig aorta amine oxidases.", "content": "Two amine oxidases have been partially purified from pig aorta and their porperties investigated: one is similar to pig plasma oxidase (benzylamine oxidase), the other to lysyloxidase. Both are inhibited by carbonyl reagents and cupric copper chelating agents, but they strongly differ in the kinetic properties. The benzylamine oxidase has a maximal reaction rate at acid pH values, the lysyloxidase has an optimum around pH 6.8.", "contents": "Partial purification of pig aorta amine oxidases. Two amine oxidases have been partially purified from pig aorta and their porperties investigated: one is similar to pig plasma oxidase (benzylamine oxidase), the other to lysyloxidase. Both are inhibited by carbonyl reagents and cupric copper chelating agents, but they strongly differ in the kinetic properties. The benzylamine oxidase has a maximal reaction rate at acid pH values, the lysyloxidase has an optimum around pH 6.8."}
{"id": "PMID:8406", "title": "Carbamylphosphate hydrolysis in donkey liver.", "content": "Mitochondria, microsomes, and cytosol all hydrolyze carbamylphosphate. Microsomes show the greatest specific activity. The mitochondrial enzyme is localized in the inner membranes, has optimum pH 5.5 and is heat-stable; the cytosol enzyme has optimum pH 5.0 and is heat-labile. Km for carbamylphosphate is 1.1 to 1.2 X 10(-2 M for both the cytosol and the mitochondrial enzyme. Both enzymes are inhibited by high substrate concentrations.", "contents": "Carbamylphosphate hydrolysis in donkey liver. Mitochondria, microsomes, and cytosol all hydrolyze carbamylphosphate. Microsomes show the greatest specific activity. The mitochondrial enzyme is localized in the inner membranes, has optimum pH 5.5 and is heat-stable; the cytosol enzyme has optimum pH 5.0 and is heat-labile. Km for carbamylphosphate is 1.1 to 1.2 X 10(-2 M for both the cytosol and the mitochondrial enzyme. Both enzymes are inhibited by high substrate concentrations."}
{"id": "PMID:8410", "title": "[Ultrastructural localization of acid phosphatase and thiamine pyrophosphatase activities and of phosphotungstic staining at low pH in the placental labyrinth of the cat].", "content": "The localizations of acid phosphatase (ACPase) and thiamine pyrophosphatase (TPPase) activities were studied in the placental labyrinth of the cat during the last days of gestation. ACPase activities were observed essentially in the syncytiotrophoblast and in the \"interstitial inert substance\" (S.I.I.) that separates maternal from foetal tissues. Reaction product was localized in lysosomes, multivesicular bodies, and in the network of smooth-membraned tubules which open on the cell surface of the syncytiotrophoblast facing the S.I.I. The S.I.I. exhibit a strong activity, probably of syncytiotrophoblastic origin. TPPase activities were found in the syncytiotrophoblast, rarely in the Golgi apparatus but always in the lumen of the network of smooth-membrande tubules. The S.I.I. shows a moderate activity. These TPPase positive tubules being frequently observed very close to the Golgi cisternae, it is proposed that they arise from the Golgi complex and convey phosphatases to the S.I.I. After phosphotungstic acid staining at low pH, luminal surface coat of maternal endothelium is always strongly and continuously visualized, while the plasma membrane of the syncytiotrophoblast facing the S.I.I. is never stained. Staining is intense in the lumen of tubules, and continuous with the stain of the S.I.I. ACPase activity of the S.I.I. could be implicated in enzymatic degradation of maternal molecules during their transfer from maternal to foetal blood. The S.I.I. may correspond to the immunological buffer zone at the interface between maternal and foetal tissues.", "contents": "[Ultrastructural localization of acid phosphatase and thiamine pyrophosphatase activities and of phosphotungstic staining at low pH in the placental labyrinth of the cat]. The localizations of acid phosphatase (ACPase) and thiamine pyrophosphatase (TPPase) activities were studied in the placental labyrinth of the cat during the last days of gestation. ACPase activities were observed essentially in the syncytiotrophoblast and in the \"interstitial inert substance\" (S.I.I.) that separates maternal from foetal tissues. Reaction product was localized in lysosomes, multivesicular bodies, and in the network of smooth-membraned tubules which open on the cell surface of the syncytiotrophoblast facing the S.I.I. The S.I.I. exhibit a strong activity, probably of syncytiotrophoblastic origin. TPPase activities were found in the syncytiotrophoblast, rarely in the Golgi apparatus but always in the lumen of the network of smooth-membrande tubules. The S.I.I. shows a moderate activity. These TPPase positive tubules being frequently observed very close to the Golgi cisternae, it is proposed that they arise from the Golgi complex and convey phosphatases to the S.I.I. After phosphotungstic acid staining at low pH, luminal surface coat of maternal endothelium is always strongly and continuously visualized, while the plasma membrane of the syncytiotrophoblast facing the S.I.I. is never stained. Staining is intense in the lumen of tubules, and continuous with the stain of the S.I.I. ACPase activity of the S.I.I. could be implicated in enzymatic degradation of maternal molecules during their transfer from maternal to foetal blood. The S.I.I. may correspond to the immunological buffer zone at the interface between maternal and foetal tissues."}
{"id": "PMID:8411", "title": "A preliminary microspectrofluorometric study of NAD(P) reduction in dibenzo(a, e) fluoranthene-treated single living cells.", "content": "The fluorescence increase, due to NAD(P) reduction, following microelectrophoretic injection of glucose 6-P (G6P) into EL2 and NCTC 8739 single living cells treated with diBenzo(ae) Fluoranthene (diB(ae)F) and non-treated, has been studied with a rapid microspectrofluorometer. This study shows the enhanced capacity of treated cells to utilize larger doses (6-10 times more) of G6P than control cells. The time course of the return to the initial fluorescence level is essentially related to the magnitude of the injection dose. There are alterations (e.g. red & blue shifts) in the fluorescence spectrum of diB(ae)F-treated cells before injection and in the increase spectrum after injection of G6P, as compared to the same spectra in the diB(ae)F-untreated cells. This is discussed in reference to the metabolization of diB(ae)F as an alternative pathway for the reoxidation of NAD(P)H.", "contents": "A preliminary microspectrofluorometric study of NAD(P) reduction in dibenzo(a, e) fluoranthene-treated single living cells. The fluorescence increase, due to NAD(P) reduction, following microelectrophoretic injection of glucose 6-P (G6P) into EL2 and NCTC 8739 single living cells treated with diBenzo(ae) Fluoranthene (diB(ae)F) and non-treated, has been studied with a rapid microspectrofluorometer. This study shows the enhanced capacity of treated cells to utilize larger doses (6-10 times more) of G6P than control cells. The time course of the return to the initial fluorescence level is essentially related to the magnitude of the injection dose. There are alterations (e.g. red & blue shifts) in the fluorescence spectrum of diB(ae)F-treated cells before injection and in the increase spectrum after injection of G6P, as compared to the same spectra in the diB(ae)F-untreated cells. This is discussed in reference to the metabolization of diB(ae)F as an alternative pathway for the reoxidation of NAD(P)H."}
{"id": "PMID:8412", "title": "Quantitative cytochemical measurement of glyceraldehyde 3-phosphate dehydrogenase activity.", "content": "A system has been developed for the quantitative measurment of glyceraldehyde 3-phosphate dehydrogenase activity in tissue sections. An obstacle to the histochemical study of this enzyme has been the fact that the substrate, gylceraldehyde 3-phosphate, is very unstable. In the present system a stable compound, fructose 1, 6-diphosphate, is used as the primary substrate and the demonsatration of the glyceraldehyde 3-phosphate dehydrogenase activity depends on the conversion of this compound into the specific substrate by the aldolase present in the tissue. The characteristics of the dehydrogenase activity resulting from the addition of fructose 1, 6-diphosphate, resemble closely the known properties of purified glyceraldehyde 3-phosphate dehydrogenase. Use of polyvinyl alcohol in the reaction medium prevents release of enzymes from the sections, as occurs in aqueous media. Although in this study intrinsic aldolase activity was found to be adequate for the rapid conversion of fructose  1, 6-diphosphate into the specific substrate for the dehydrogenase, the use of exogenous aldolase may be of particular advantage in assessing the intergrity of the Embden-Meyerhof pathway.", "contents": "Quantitative cytochemical measurement of glyceraldehyde 3-phosphate dehydrogenase activity. A system has been developed for the quantitative measurment of glyceraldehyde 3-phosphate dehydrogenase activity in tissue sections. An obstacle to the histochemical study of this enzyme has been the fact that the substrate, gylceraldehyde 3-phosphate, is very unstable. In the present system a stable compound, fructose 1, 6-diphosphate, is used as the primary substrate and the demonsatration of the glyceraldehyde 3-phosphate dehydrogenase activity depends on the conversion of this compound into the specific substrate by the aldolase present in the tissue. The characteristics of the dehydrogenase activity resulting from the addition of fructose 1, 6-diphosphate, resemble closely the known properties of purified glyceraldehyde 3-phosphate dehydrogenase. Use of polyvinyl alcohol in the reaction medium prevents release of enzymes from the sections, as occurs in aqueous media. Although in this study intrinsic aldolase activity was found to be adequate for the rapid conversion of fructose  1, 6-diphosphate into the specific substrate for the dehydrogenase, the use of exogenous aldolase may be of particular advantage in assessing the intergrity of the Embden-Meyerhof pathway."}
{"id": "PMID:8413", "title": "Protocol management of male genitourinary infections.", "content": "As part of a demonstration study, 567 male patients presenting to a \"walk-in\" clinic with common genitourinary complaints were interviewed by health assistants guided by a protocol. Independent examination of 19 patients by a health assistant and a physician formally demonstrated that the health assistants could collect the clinical data accurately. Forty-four patients were then randomly chosen to be examined, diagnosed and treated either by a health assistant guided by the protocol and supported by an available physician, or only by a physician. Using medical records and a follow-up interview, we assessed the thoroughness of the medical record, adequacy of diagnosis and treatment, symptom relief, patient satisfaction and patient education: the health assistant-protocol system proved as safe and effective as the MD-only system, and the health assistants were able to manage 68% of patients without involving the physician. The study suggests that briefly-trained health assistants may help save physician and nurse time, and that the development of protocols can help set standards for the medical management of defined problems while providing a mechanism for rapidly creating a complete medical record which can be easily audited for conformance with standards.", "contents": "Protocol management of male genitourinary infections. As part of a demonstration study, 567 male patients presenting to a \"walk-in\" clinic with common genitourinary complaints were interviewed by health assistants guided by a protocol. Independent examination of 19 patients by a health assistant and a physician formally demonstrated that the health assistants could collect the clinical data accurately. Forty-four patients were then randomly chosen to be examined, diagnosed and treated either by a health assistant guided by the protocol and supported by an available physician, or only by a physician. Using medical records and a follow-up interview, we assessed the thoroughness of the medical record, adequacy of diagnosis and treatment, symptom relief, patient satisfaction and patient education: the health assistant-protocol system proved as safe and effective as the MD-only system, and the health assistants were able to manage 68% of patients without involving the physician. The study suggests that briefly-trained health assistants may help save physician and nurse time, and that the development of protocols can help set standards for the medical management of defined problems while providing a mechanism for rapidly creating a complete medical record which can be easily audited for conformance with standards."}
{"id": "PMID:8414", "title": "Gardimycin, a new antibiotic from Actinoplanes. III. Biological properties.", "content": "The new antibiotic gardimycin has an interesting in vitro antibacterial activity against Gram-positive bacteria and Neisseria gonorrhoeae. Parenteral administration gives a high degree of protection against experimental infections in mice. It also shows some chemotherapeutic activity when given rectally.", "contents": "Gardimycin, a new antibiotic from Actinoplanes. III. Biological properties. The new antibiotic gardimycin has an interesting in vitro antibacterial activity against Gram-positive bacteria and Neisseria gonorrhoeae. Parenteral administration gives a high degree of protection against experimental infections in mice. It also shows some chemotherapeutic activity when given rectally."}
{"id": "PMID:8415", "title": "Inhibitory activity of pyridindolol on beta-galactosidase.", "content": "The activity of pyridindolol in inhibiting beta-galactosidases obtained from various sources has been studied. Whereas acid bovine liver beta-galactosidase (optimal pH 4.0) was not affected by this compound, neutral bovine liver beta-galactosidase (pH-optimum = 7.0) was inhibited by pyridindolol in reaction mixtures of pH 4.0 approximately 5.0. There was no inhibition at pH 7.0. The type of inhibition is non-competitive by formation of a pyridindolol-enzyme complex. Since beta-galactosidases from other sources are not affected by pyridindolol, the inhibitory action of this compound seems to be rather specific for neutral bovine liver beta-galactosidase.", "contents": "Inhibitory activity of pyridindolol on beta-galactosidase. The activity of pyridindolol in inhibiting beta-galactosidases obtained from various sources has been studied. Whereas acid bovine liver beta-galactosidase (optimal pH 4.0) was not affected by this compound, neutral bovine liver beta-galactosidase (pH-optimum = 7.0) was inhibited by pyridindolol in reaction mixtures of pH 4.0 approximately 5.0. There was no inhibition at pH 7.0. The type of inhibition is non-competitive by formation of a pyridindolol-enzyme complex. Since beta-galactosidases from other sources are not affected by pyridindolol, the inhibitory action of this compound seems to be rather specific for neutral bovine liver beta-galactosidase."}
{"id": "PMID:8416", "title": "Selective N-actylation of gentamicin antibiotics-synthesis of 1-N-acyl derivatives.", "content": "Treatment of acid addition salts of aminoglycoside-aminocyclitol antibiotics of the gentamicin-sisomicin class, with one equivalent of triethylamine and an acylating agent results in selective formation of 1-N-acyl derivatives. This is in contrast to acylation of the antibiotic free bases which results in preferential acylation of other basic centres in the molecule. Origins of the observed selectivity are discussed. In vitro antibacterial activities of several new 1-N-acy1 derivatives of gentamicin, sisomicin and verdamicin are reported.", "contents": "Selective N-actylation of gentamicin antibiotics-synthesis of 1-N-acyl derivatives. Treatment of acid addition salts of aminoglycoside-aminocyclitol antibiotics of the gentamicin-sisomicin class, with one equivalent of triethylamine and an acylating agent results in selective formation of 1-N-acyl derivatives. This is in contrast to acylation of the antibiotic free bases which results in preferential acylation of other basic centres in the molecule. Origins of the observed selectivity are discussed. In vitro antibacterial activities of several new 1-N-acy1 derivatives of gentamicin, sisomicin and verdamicin are reported."}
{"id": "PMID:8419", "title": "Propagated spikes and secretion in a coelenterate glandular epithelium.", "content": "The rete mirabile of Hippopodius (Cl. Hydrozoa, O. Siphonophora) is a sheet of giant endoderm cells penetrated by branches of the ventral radial canal. The cells appear to be highly polyploid. The rough ER is very richly developed and expanded ER cisternae containing amorphous material (presumably synthesized protein) are observed near the outer cell surface. The cells are electrically coupled, and are connected by gap junctions. The rete is electrically excitable and cell to cell conduction of action potentials at 10 cm/s is observed. The action potentials are all-or-none, positive-going events, showing amplitudes of about 70 mV and arising from a 44 mV resting potential. Slowly developing and decaying secondary depolarizations, capable of summing to the 20 mV level, are also observed. After passage of a train of impulses, the rete cells swell and secretion drops appear at the surface, these changes becoming apparent within a few seconds. In 15 mM Mn2+ the response fails to occur, and secondary depolarizations (\"secretion potentials\") are not seen. Spike propagation is not affected. In Na+-free solutions the spikes are reduced and propagation eventually fails. It is suggested that the spikes are sodium-dependent events which trigger a calcium-dependent secretory process. The composition and biological activity of the secretion are uncertain, but indirect evidence suggests a possible defensive or repellant role for the response.", "contents": "Propagated spikes and secretion in a coelenterate glandular epithelium. The rete mirabile of Hippopodius (Cl. Hydrozoa, O. Siphonophora) is a sheet of giant endoderm cells penetrated by branches of the ventral radial canal. The cells appear to be highly polyploid. The rough ER is very richly developed and expanded ER cisternae containing amorphous material (presumably synthesized protein) are observed near the outer cell surface. The cells are electrically coupled, and are connected by gap junctions. The rete is electrically excitable and cell to cell conduction of action potentials at 10 cm/s is observed. The action potentials are all-or-none, positive-going events, showing amplitudes of about 70 mV and arising from a 44 mV resting potential. Slowly developing and decaying secondary depolarizations, capable of summing to the 20 mV level, are also observed. After passage of a train of impulses, the rete cells swell and secretion drops appear at the surface, these changes becoming apparent within a few seconds. In 15 mM Mn2+ the response fails to occur, and secondary depolarizations (\"secretion potentials\") are not seen. Spike propagation is not affected. In Na+-free solutions the spikes are reduced and propagation eventually fails. It is suggested that the spikes are sodium-dependent events which trigger a calcium-dependent secretory process. The composition and biological activity of the secretion are uncertain, but indirect evidence suggests a possible defensive or repellant role for the response."}
{"id": "PMID:8420", "title": "Respiratory adaptations in burrowing pocket gophers from sea level and high altitude.", "content": "To examine the adaptations to low O2 and high CO2 among fossorial and nonfossorial rodents, hematological parameters were determined for laboratory rats, the valley pocket gopher (Thomomys bottae) from 250 m, and the mountain pocket gopher (T. umbrinus melanotis) from 3150 m. Hematocrit, hemoglobin concentration, and O2 capacity were higher in pocket gophers than in rats. Blood PO2 at 50% saturation and pH 7.4 was 33 mmHg for both gophers and 39 mmHg for rats. Bohr factors for all three rodents were similar (-0.55 to -0.61) but buffer value, delta log PCO2/delta pH, was -2.54 for T. umbrinus, -1.97 for T. bottae, and -0.98 for Rattus. Concentrations of total acid-soluble phosphates were 50-75% higher in gophers than in rats, while bicarbonate values were within the normal mammalian range. All three rodents had similar myoglobin concentrations in cardiac muscle. Myoglobin concentrations were significantly higher in skeletal muscles (diaphragm, gastrocnemius) of T. umbrinus when compared to T. bottae, and significantly higher in both gophers when compared to rats. These differences may constitute important adaptations to the hypoxia and hypercapnia in burrows; certain of these factors in pocket gophers respond to the additional stress of high altitude hypoxia.", "contents": "Respiratory adaptations in burrowing pocket gophers from sea level and high altitude. To examine the adaptations to low O2 and high CO2 among fossorial and nonfossorial rodents, hematological parameters were determined for laboratory rats, the valley pocket gopher (Thomomys bottae) from 250 m, and the mountain pocket gopher (T. umbrinus melanotis) from 3150 m. Hematocrit, hemoglobin concentration, and O2 capacity were higher in pocket gophers than in rats. Blood PO2 at 50% saturation and pH 7.4 was 33 mmHg for both gophers and 39 mmHg for rats. Bohr factors for all three rodents were similar (-0.55 to -0.61) but buffer value, delta log PCO2/delta pH, was -2.54 for T. umbrinus, -1.97 for T. bottae, and -0.98 for Rattus. Concentrations of total acid-soluble phosphates were 50-75% higher in gophers than in rats, while bicarbonate values were within the normal mammalian range. All three rodents had similar myoglobin concentrations in cardiac muscle. Myoglobin concentrations were significantly higher in skeletal muscles (diaphragm, gastrocnemius) of T. umbrinus when compared to T. bottae, and significantly higher in both gophers when compared to rats. These differences may constitute important adaptations to the hypoxia and hypercapnia in burrows; certain of these factors in pocket gophers respond to the additional stress of high altitude hypoxia."}
{"id": "PMID:8421", "title": "Control of breathing in uremia: ventilatory response to CO2 after hemodialysis.", "content": "The mechanisms responsible for the transient respiratory alkalosis which follows clinical hemodialysis were evaluated by studying the ventilatory response to carbon dioxide in chronic uremic patients, and in unanesthetized normal and chronic uremic goats. A significant increase in sensitivity to CO2 was found in acidotic uremic patients immediately (within 30 min) following hemodialysis (P less than 0.01). Sensitivity to CO2 returned to the predialysis value within 24 h. Lung volume and maximal breathing capacity were unchanged. A similar increase in sensitivity to CO2 was seen in nonacidotic uremic goats following hemodialysis. In the goats, these changes in sensitivity could not be explained by changes in cerebrospinal fluid acid-base status. Adding sufficient urea to the dialysate to prevent a fall in plasma urea concentration, eliminated this increase in sensitivity to CO2 in both uremic patients and goats. These results suggests that the transient respiratory alkalosis following hemodialysis is due to an increase in the sensitivity of the ventilatory response to carbon dioxide and is a consequence of dialysis-induced osmotic disequilibrium.", "contents": "Control of breathing in uremia: ventilatory response to CO2 after hemodialysis. The mechanisms responsible for the transient respiratory alkalosis which follows clinical hemodialysis were evaluated by studying the ventilatory response to carbon dioxide in chronic uremic patients, and in unanesthetized normal and chronic uremic goats. A significant increase in sensitivity to CO2 was found in acidotic uremic patients immediately (within 30 min) following hemodialysis (P less than 0.01). Sensitivity to CO2 returned to the predialysis value within 24 h. Lung volume and maximal breathing capacity were unchanged. A similar increase in sensitivity to CO2 was seen in nonacidotic uremic goats following hemodialysis. In the goats, these changes in sensitivity could not be explained by changes in cerebrospinal fluid acid-base status. Adding sufficient urea to the dialysate to prevent a fall in plasma urea concentration, eliminated this increase in sensitivity to CO2 in both uremic patients and goats. These results suggests that the transient respiratory alkalosis following hemodialysis is due to an increase in the sensitivity of the ventilatory response to carbon dioxide and is a consequence of dialysis-induced osmotic disequilibrium."}
{"id": "PMID:8422", "title": "Characteristics and energy requirements of an alpha-aminoisobutyric acid transport system in Streptococcus lactis.", "content": "Galactose-grown cells of Streptococcus lactis ML3 acculated alpha-aminoisobutyric acid (AIB) by using energy derived from glycolysis and arginine catabolism. The transport system displayed low-affinity Michaelis-Menten saturation kinetics. Using galactose or arginine as energy sources, similar V max and K m values for AIB entry were obtained, but on prolonged incubation the intracellular steady-state concentration of AIB in cells metabolizing arginine was only 65 to 70% that attained by glycolyzing cells. Efflux of AIB FROM PRELOADED CElls was temperature dependent and exhibited the characteristics of a first-order reaction. The rate of AIB exit was accelerated two- to threefold in the presence of metabolizable energy sources. Metabolic inhibitors including p-chloromercuribenzoate, dinitrophenol, azide, arsentate, and N, N'-dicyclohexylcarbodiimide either prevented or greatly reduced AIB uptake. Fluoride, iodoacetate and N-ethylmaleimide abolished galactose-dependent, but not arginine-energized, AIB uptake. K+ and Rb+ reduced the steady-state intracellular AIB concentration by approximately 40%, and these cations also induced rapid efflux of solute from actively transporting cells. Equivalent concentrations (10 mM) of Na+, Li+, or NH4+ were much less inhibitory. The proton-conducting ionophores tetrachlorosalicylanilide and carbonylcyanide m-chlorophenlyhydrazone abolished uptake and induced AIB efflux even though glycolysis and arginine catabolism continued at 60 and 140%, respectively, of control rates. A proton motive force is most likely involved in the active transport of AIB, whereas data from efflux studies suggest that energy is coupled to AIB exit in cells of S. lactis ML3.", "contents": "Characteristics and energy requirements of an alpha-aminoisobutyric acid transport system in Streptococcus lactis. Galactose-grown cells of Streptococcus lactis ML3 acculated alpha-aminoisobutyric acid (AIB) by using energy derived from glycolysis and arginine catabolism. The transport system displayed low-affinity Michaelis-Menten saturation kinetics. Using galactose or arginine as energy sources, similar V max and K m values for AIB entry were obtained, but on prolonged incubation the intracellular steady-state concentration of AIB in cells metabolizing arginine was only 65 to 70% that attained by glycolyzing cells. Efflux of AIB FROM PRELOADED CElls was temperature dependent and exhibited the characteristics of a first-order reaction. The rate of AIB exit was accelerated two- to threefold in the presence of metabolizable energy sources. Metabolic inhibitors including p-chloromercuribenzoate, dinitrophenol, azide, arsentate, and N, N'-dicyclohexylcarbodiimide either prevented or greatly reduced AIB uptake. Fluoride, iodoacetate and N-ethylmaleimide abolished galactose-dependent, but not arginine-energized, AIB uptake. K+ and Rb+ reduced the steady-state intracellular AIB concentration by approximately 40%, and these cations also induced rapid efflux of solute from actively transporting cells. Equivalent concentrations (10 mM) of Na+, Li+, or NH4+ were much less inhibitory. The proton-conducting ionophores tetrachlorosalicylanilide and carbonylcyanide m-chlorophenlyhydrazone abolished uptake and induced AIB efflux even though glycolysis and arginine catabolism continued at 60 and 140%, respectively, of control rates. A proton motive force is most likely involved in the active transport of AIB, whereas data from efflux studies suggest that energy is coupled to AIB exit in cells of S. lactis ML3."}
{"id": "PMID:8423", "title": "Deoxyribonucleic acid-binding studies on the hut repressor and mutant forms of the hut repressor of Salmonella typhimurium.", "content": "In Salmonella typhimurium the genes coding for the enzymes of histidine utilization (hut) are clustered in two adjacent operons, hutMIGC and hut(P,R,Q)UH. A single repressor, the product of the C gene, regulates both operons by binding at two operator sites, one near M and one in (P,R,Q). The deoxyribonucleic acid (DNA)-binding activity of the repressor was measured using DNA's containing separate operators. The repressor had greater activity when assayed using DNA containing the operator of the (P,R,Q)UH operon than when assayed using DNA containing the operator of the MIGC operon. The binding to either operator was absent in the presence of the inducer, urocanate. The DNA-binding activities were also determined for two super-repressors. The super-repressors had altered DNA-binding properties, although the self-regulated nature of the repressors complicated the analysis of the results. A purfication procedure for the wild-type repressor is presented. The purified repressor was somewhat unstable, and additional experiments using it were not performed.", "contents": "Deoxyribonucleic acid-binding studies on the hut repressor and mutant forms of the hut repressor of Salmonella typhimurium. In Salmonella typhimurium the genes coding for the enzymes of histidine utilization (hut) are clustered in two adjacent operons, hutMIGC and hut(P,R,Q)UH. A single repressor, the product of the C gene, regulates both operons by binding at two operator sites, one near M and one in (P,R,Q). The deoxyribonucleic acid (DNA)-binding activity of the repressor was measured using DNA's containing separate operators. The repressor had greater activity when assayed using DNA containing the operator of the (P,R,Q)UH operon than when assayed using DNA containing the operator of the MIGC operon. The binding to either operator was absent in the presence of the inducer, urocanate. The DNA-binding activities were also determined for two super-repressors. The super-repressors had altered DNA-binding properties, although the self-regulated nature of the repressors complicated the analysis of the results. A purfication procedure for the wild-type repressor is presented. The purified repressor was somewhat unstable, and additional experiments using it were not performed."}
{"id": "PMID:8424", "title": "Purification of properties of dihydroorotase, a zinc-containing metalloenzyme in Clostridium oroticum.", "content": "Dihydroorotase +4,5-L-dihydro-orotate amidohydrolase [EC 3.5.2.3]), which catalyzes the reversible cyclization of N-carbamyl-L-aspartate to L-dihydroorotate, has been purified from orotate-grown Clostridium oroticum. The enzyme is homogeneous when subjected to polyacrylamide gel electrophoresis and is stable at pH 7.6 in 0.3 M NaCl containing 10 muM ZnSO4. The enzyme has a molecular weight of approximately 110,000. Sodium dodecyl sulfate gel electrophoresis, using three different buffer systems, indicated the enzyme is composed of two subunits, each having a molecular weight of 55,000. Dihydroorotase is shown by atomic absorption spectroscopy to be a zinc-containing metalloenzyme with 4 g-atoms of zinc per 110,000 g of protein. The pH optima for the conversion of N-carbamyl-L-aspartate to L-dihydroorotate and for L-dihydroorotate to N-carbamyl-L-aspartate are pH 6.0 and 8.2, respectively. The Km values for N-carbamyl-L-aspartate and for L-dihydroorotate are 0.13 and 0.07 mM, respectively. Inhibitor studies indicate that zinc may be involved in the catalytic activity of the enzyme.", "contents": "Purification of properties of dihydroorotase, a zinc-containing metalloenzyme in Clostridium oroticum. Dihydroorotase +4,5-L-dihydro-orotate amidohydrolase [EC 3.5.2.3]), which catalyzes the reversible cyclization of N-carbamyl-L-aspartate to L-dihydroorotate, has been purified from orotate-grown Clostridium oroticum. The enzyme is homogeneous when subjected to polyacrylamide gel electrophoresis and is stable at pH 7.6 in 0.3 M NaCl containing 10 muM ZnSO4. The enzyme has a molecular weight of approximately 110,000. Sodium dodecyl sulfate gel electrophoresis, using three different buffer systems, indicated the enzyme is composed of two subunits, each having a molecular weight of 55,000. Dihydroorotase is shown by atomic absorption spectroscopy to be a zinc-containing metalloenzyme with 4 g-atoms of zinc per 110,000 g of protein. The pH optima for the conversion of N-carbamyl-L-aspartate to L-dihydroorotate and for L-dihydroorotate to N-carbamyl-L-aspartate are pH 6.0 and 8.2, respectively. The Km values for N-carbamyl-L-aspartate and for L-dihydroorotate are 0.13 and 0.07 mM, respectively. Inhibitor studies indicate that zinc may be involved in the catalytic activity of the enzyme."}
{"id": "PMID:8425", "title": "Influence of amino acids on the growth of Bacteroides melaninogenicus.", "content": "Addition of individual amino acids to a Trypticase-yeast extract-hemin medium affected growth rates and final yields of an asaccharolytic strain and a saccharolytic strain of Bacteroides melaninogenicus. L-Aspartate or L-asparagine produced maximal growth enhancement for both strains. L-[14C]aspartate was fermented by resting cells of the asaccharolytic strain. L-Cysteine or L-serine also enhanced growth for the saccharolytic strain. However, growth of the saccharolytic strain was inhibited by L-lysine, L-glutamate, L-glutamine, L-isoleucine, L-leucine, and L-proline; growth of the asaccharolytic strain was inhibited by DL-valine and L-serine. Both strains were inhibited by L-histidine, DL-methionine, L-tryptophan, L-arginine, and glycine.", "contents": "Influence of amino acids on the growth of Bacteroides melaninogenicus. Addition of individual amino acids to a Trypticase-yeast extract-hemin medium affected growth rates and final yields of an asaccharolytic strain and a saccharolytic strain of Bacteroides melaninogenicus. L-Aspartate or L-asparagine produced maximal growth enhancement for both strains. L-[14C]aspartate was fermented by resting cells of the asaccharolytic strain. L-Cysteine or L-serine also enhanced growth for the saccharolytic strain. However, growth of the saccharolytic strain was inhibited by L-lysine, L-glutamate, L-glutamine, L-isoleucine, L-leucine, and L-proline; growth of the asaccharolytic strain was inhibited by DL-valine and L-serine. Both strains were inhibited by L-histidine, DL-methionine, L-tryptophan, L-arginine, and glycine."}
{"id": "PMID:8426", "title": "Constitutive and repressivle enzymes of the common pathway of aromatic biosynthesis in Escherichia coli K-12: regulation of enzyme synthesis at different growth rates.", "content": "Synthesis of five of the enzymes of the common pathway of aromatic biosynthesis has been shown to be unaffected by either the aromatic amino acids--the product of the first reaction (3-deoxy-D-arabinoheptulosonic acid-7-phosphate) or the product of the last reaction (chorismate)--or by the state of regulator gene loci tyrR. On the other hand, the rate of synthesis of these enzymes, and of several other enzymes for which repression control was inactive because of mutations in relevant regulator genes, was found to change with growth rate. These changes were found to correlate at faster growth rates than those observed in glucose minimal medium with the alterations in the relative frequencies of the corresponding structural genes which occur at these growth rates. It was found that when wild-type cells were grown at these faster growth rates in medium lacking the aromatic amino acids, complete derepression of the tyrosine-inhibitable 3-deoxy-D-arabinoheptulosonic acid-7-phosphate synthetase occurred, in strong contrast to the situation when wild-type cells are grown in glucose minimal medium.", "contents": "Constitutive and repressivle enzymes of the common pathway of aromatic biosynthesis in Escherichia coli K-12: regulation of enzyme synthesis at different growth rates. Synthesis of five of the enzymes of the common pathway of aromatic biosynthesis has been shown to be unaffected by either the aromatic amino acids--the product of the first reaction (3-deoxy-D-arabinoheptulosonic acid-7-phosphate) or the product of the last reaction (chorismate)--or by the state of regulator gene loci tyrR. On the other hand, the rate of synthesis of these enzymes, and of several other enzymes for which repression control was inactive because of mutations in relevant regulator genes, was found to change with growth rate. These changes were found to correlate at faster growth rates than those observed in glucose minimal medium with the alterations in the relative frequencies of the corresponding structural genes which occur at these growth rates. It was found that when wild-type cells were grown at these faster growth rates in medium lacking the aromatic amino acids, complete derepression of the tyrosine-inhibitable 3-deoxy-D-arabinoheptulosonic acid-7-phosphate synthetase occurred, in strong contrast to the situation when wild-type cells are grown in glucose minimal medium."}
{"id": "PMID:8427", "title": "Characterization of L-asparagine transport systems in Stemphylium botryosum.", "content": "L-Asparagine uptake by Stemphylium botryosum is mediated by two distinct energy- and temperature-dependent transport systems. One permease is relatively specific for L-asparagine and L-glutamine and is present in nutrient-sufficient mycelium. The specific permease shows an optimum pH at 5.2, saturation kinetics (Km = 4.4 x 10(-4) M, Vmax = 1.1 mumol/g per min), competitive gradient of L-asparagine, and higher affinity towards the L-isomer of asparagine. Amide derivatives of L-asparagine (5-diazo-4-oxo-L-norvaline or L-aspartyl hydroxamate) are the most effective competitors, alpha-amino derivative (N-acetyl asparagine) is a moderate competitor, and alpha-carboxyl derivative (L-asparagine-t-butylester) shows only slight inhibition of the specific permease. Derivatives of L-glutamine are significantly less effective competitors than those of L-asparatine. The level of the specific permease is affected by nitrogen sources and increases approximately threefold upon starvation. The nonspecific permease possesses an optimum pH at 6.8, saturation kinetics (Km = 7 x 10(-5) M, Vmax = 5 mumol/g per min, Kt = 7.4 x 10(-5) M for L-leucine), and high affinity towards various types of amino acids.", "contents": "Characterization of L-asparagine transport systems in Stemphylium botryosum. L-Asparagine uptake by Stemphylium botryosum is mediated by two distinct energy- and temperature-dependent transport systems. One permease is relatively specific for L-asparagine and L-glutamine and is present in nutrient-sufficient mycelium. The specific permease shows an optimum pH at 5.2, saturation kinetics (Km = 4.4 x 10(-4) M, Vmax = 1.1 mumol/g per min), competitive gradient of L-asparagine, and higher affinity towards the L-isomer of asparagine. Amide derivatives of L-asparagine (5-diazo-4-oxo-L-norvaline or L-aspartyl hydroxamate) are the most effective competitors, alpha-amino derivative (N-acetyl asparagine) is a moderate competitor, and alpha-carboxyl derivative (L-asparagine-t-butylester) shows only slight inhibition of the specific permease. Derivatives of L-glutamine are significantly less effective competitors than those of L-asparatine. The level of the specific permease is affected by nitrogen sources and increases approximately threefold upon starvation. The nonspecific permease possesses an optimum pH at 6.8, saturation kinetics (Km = 7 x 10(-5) M, Vmax = 5 mumol/g per min, Kt = 7.4 x 10(-5) M for L-leucine), and high affinity towards various types of amino acids."}
{"id": "PMID:8428", "title": "Synthesis of omega-alicyclic fatty acids from cyclic precursors in Bacillus subtilis.", "content": "A mutant of Bacillus subtilis synthesizes a variety of omega-alicyclic fatty acids when fed with the respective alicyclic carboxylic acids. These fatty acids are: omega-cyclopropane, omega-cyclobutane, omega-cyclopentane, omega-cyclohexane, and omega-cyclohexene fatty acids. These unusual fatty acids did not lead to an inhibition of growth at 37 degrees C and pH 7. The selective advantage of these fatty acids under extrene conditions was studied in comparison with the acidophilic, thermophilic bacterium B. acidocaldarius, which normally contains a high proportion of omega-cyclohexane fatty acids.", "contents": "Synthesis of omega-alicyclic fatty acids from cyclic precursors in Bacillus subtilis. A mutant of Bacillus subtilis synthesizes a variety of omega-alicyclic fatty acids when fed with the respective alicyclic carboxylic acids. These fatty acids are: omega-cyclopropane, omega-cyclobutane, omega-cyclopentane, omega-cyclohexane, and omega-cyclohexene fatty acids. These unusual fatty acids did not lead to an inhibition of growth at 37 degrees C and pH 7. The selective advantage of these fatty acids under extrene conditions was studied in comparison with the acidophilic, thermophilic bacterium B. acidocaldarius, which normally contains a high proportion of omega-cyclohexane fatty acids."}
{"id": "PMID:8429", "title": "Isolation and characterization of dihydropteridine reductase from Pseudomonas species.", "content": "Dihydropteridine reductase isolated from the bacterium Pseudomonas species (ATCC 11299a) has been purified approximately 450-fold byammonium sulfate precipitation and diethylaminoethyl-cellulose chromatographic procedures. The preparation is at least 80% pure as judged by polyacrylamide gels. Its molecular weight was determined to be about 44,000. Both dihydropteridine reductase and phenylalanine hydroxylase activities were found to be higher in cells adapted to a medium containing L-phenylalanine or L-tyrosine as the sole carbon source than in those grown in L-asparagine. The substrate of the reductase is quinonoid dihydropteridine, and the product is tentatively identified as a tetrahydropteridine through its ability to serve as a cofactor for phenylalanine hydroxylase. The enzyme shows no marked specificity for the pteridine cofactor that occurs naturally in this organism, L-threo-neopterin. The pH optimum for the reductase is 7.2, and nicotinamide adenine dinucleotide, reduced form, is the preferred cosubstrate. Inhibition of the reduced and untreated enzyme by several sulfhydryl reagents was observed. A metal requirement for the reductase could not be demonstrated. Dihydropteridine reductase was found to be inhibited by aminopterin in a competitive manner with respect to the quinonoid dihydro form of 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine.", "contents": "Isolation and characterization of dihydropteridine reductase from Pseudomonas species. Dihydropteridine reductase isolated from the bacterium Pseudomonas species (ATCC 11299a) has been purified approximately 450-fold byammonium sulfate precipitation and diethylaminoethyl-cellulose chromatographic procedures. The preparation is at least 80% pure as judged by polyacrylamide gels. Its molecular weight was determined to be about 44,000. Both dihydropteridine reductase and phenylalanine hydroxylase activities were found to be higher in cells adapted to a medium containing L-phenylalanine or L-tyrosine as the sole carbon source than in those grown in L-asparagine. The substrate of the reductase is quinonoid dihydropteridine, and the product is tentatively identified as a tetrahydropteridine through its ability to serve as a cofactor for phenylalanine hydroxylase. The enzyme shows no marked specificity for the pteridine cofactor that occurs naturally in this organism, L-threo-neopterin. The pH optimum for the reductase is 7.2, and nicotinamide adenine dinucleotide, reduced form, is the preferred cosubstrate. Inhibition of the reduced and untreated enzyme by several sulfhydryl reagents was observed. A metal requirement for the reductase could not be demonstrated. Dihydropteridine reductase was found to be inhibited by aminopterin in a competitive manner with respect to the quinonoid dihydro form of 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine."}
{"id": "PMID:8430", "title": "Factors affecting growth and nitrogen fixation of Spirillum lipoferum.", "content": "Spirillum lipoferum grows vigorously on malate, succinate, lactate, or pyruvate, moderately on galactose or acetate, and poorly on glucose or citrate. It reduces 15N2. Acetylene reduction rates decrease rapidly when the pH of the culture rises above 7.8. The organism is highly aerobic and had doubling times as low as 2 h when grown on NH4+. However, S. lipoferum reduces N2 well only under microaerophilic conditions. The optimal pO2 for acetylene reduction by stagnant cultures was 0.006 to 0.02 atm depending upon the cell density; aerated cultures grew well at dissolved O2 concentration corresponding to a pO2 of about 0.008 atm. Shaking S. lipoferum with air temporarily inactivates its nitrogenase; reactivation is inhibited by chloramphenicol. The organism assimilated 20 to 24 mg of N/g of organic acid oxidized during growth. The strains studied can be placed in two groups based upon their morphology and physiological characteristics.", "contents": "Factors affecting growth and nitrogen fixation of Spirillum lipoferum. Spirillum lipoferum grows vigorously on malate, succinate, lactate, or pyruvate, moderately on galactose or acetate, and poorly on glucose or citrate. It reduces 15N2. Acetylene reduction rates decrease rapidly when the pH of the culture rises above 7.8. The organism is highly aerobic and had doubling times as low as 2 h when grown on NH4+. However, S. lipoferum reduces N2 well only under microaerophilic conditions. The optimal pO2 for acetylene reduction by stagnant cultures was 0.006 to 0.02 atm depending upon the cell density; aerated cultures grew well at dissolved O2 concentration corresponding to a pO2 of about 0.008 atm. Shaking S. lipoferum with air temporarily inactivates its nitrogenase; reactivation is inhibited by chloramphenicol. The organism assimilated 20 to 24 mg of N/g of organic acid oxidized during growth. The strains studied can be placed in two groups based upon their morphology and physiological characteristics."}
{"id": "PMID:8431", "title": "Ornithine delta-transaminase activity in Escherichia coli: its identity with acetylornithine delta-transaminase.", "content": "Procedures that have been developed for the purification of acetylornithine delta-transaminase from Escherichia coli W also lead to the simultaneous purification of ornithine delta-transaminase. These two enzymatic activities have the same electrophoretic mobility and are identical immunochemically. Studies of inhibition kinetics demonstrate that the two substrates, acetylornithine and ornithine, compete for the same active site of acetylornithine delta-transaminase; thus, the ornithine delta-transaminase activity in E coli is due to acetylornithine delta-transaminase and not to a separate specific ornithine delta-transaminase.", "contents": "Ornithine delta-transaminase activity in Escherichia coli: its identity with acetylornithine delta-transaminase. Procedures that have been developed for the purification of acetylornithine delta-transaminase from Escherichia coli W also lead to the simultaneous purification of ornithine delta-transaminase. These two enzymatic activities have the same electrophoretic mobility and are identical immunochemically. Studies of inhibition kinetics demonstrate that the two substrates, acetylornithine and ornithine, compete for the same active site of acetylornithine delta-transaminase; thus, the ornithine delta-transaminase activity in E coli is due to acetylornithine delta-transaminase and not to a separate specific ornithine delta-transaminase."}
{"id": "PMID:8432", "title": "Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus.", "content": "A stable deoxyribonucleic acid (DNA) polymerase (EC 2.7.7.7) with a temperature optimum of 80 degrees C has been purified from the extreme thermophile Thermus aquaticus. The enzyme is free from phosphomonoesterase, phosphodiesterase and single-stranded exonuclease activities. Maximal activity of the enzyme requires all four deoxyribonucleotides and activated calf thymus DNA. An absolute requirement for divalent cation cofactor was satisfied by Mg2+ or to a lesser extent by Mn2+. Monovalent cations at concentrations as high as 0.1 M did not show a significant inhibitory effect. The pH optimum was 8.0 in tris(hydroxymethyl)aminomethane-hydrochloride buffer. The molecular weight of the enzyme was estimated by sucrose gradient centrifugation and gel filtrations on Sephadex G-100 to be approximately 63,000 to 68,000. The elevated temperature requirement, small size, and lack of nuclease activity distinguish this polymerase from the DNA polymerase of Escherichia coli.", "contents": "Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus. A stable deoxyribonucleic acid (DNA) polymerase (EC 2.7.7.7) with a temperature optimum of 80 degrees C has been purified from the extreme thermophile Thermus aquaticus. The enzyme is free from phosphomonoesterase, phosphodiesterase and single-stranded exonuclease activities. Maximal activity of the enzyme requires all four deoxyribonucleotides and activated calf thymus DNA. An absolute requirement for divalent cation cofactor was satisfied by Mg2+ or to a lesser extent by Mn2+. Monovalent cations at concentrations as high as 0.1 M did not show a significant inhibitory effect. The pH optimum was 8.0 in tris(hydroxymethyl)aminomethane-hydrochloride buffer. The molecular weight of the enzyme was estimated by sucrose gradient centrifugation and gel filtrations on Sephadex G-100 to be approximately 63,000 to 68,000. The elevated temperature requirement, small size, and lack of nuclease activity distinguish this polymerase from the DNA polymerase of Escherichia coli."}
{"id": "PMID:8433", "title": "Studies on peroxisomes. VI. Relationship between the peroxisomal core and urate oxidase.", "content": "The peroxisomal core from the liver of rats was purified 450-fold as a marker of urate oxidase [EC 1.7.3.3.] activity. This preparation has a high specific activity of urate oxidase but not of other peroxisomal enzymes: D-amino acid oxidase [EC 1.4.3.3.], L-alpha-hydroxy acid oxidase [EC 1.1.3.15], or catalase [EC 1.11.1.6]. No activity of marker enzymes for other subcellular particles; cytochrome c oxidase [EC1.9.3.1] (mitochondria), acid phosphatase [EC 3.1.3.2] (lysosomes), or glucose-6-phosphatase [EC 3.1.3.9] (microsomes), was detected in this preparation. The core obtained showed a single protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the position of the band was found to correspond to a molecular weight 35,000. When the peroxisomal core was subjected to treatment at various pH's with 0.1 M carbonate buffer, urate oxidase was almost completely solubulized at pH 11.0, although approximately 35% of the core protein still remained in the pellet After solubilization of the core at pH 11.0, the specific activity of urate oxidase in the supernatant increased about 1.6 times; the density of the insoluble protein remaining in the pellet was identical with the that of the original core on sucrose density gradient centrifugation.", "contents": "Studies on peroxisomes. VI. Relationship between the peroxisomal core and urate oxidase. The peroxisomal core from the liver of rats was purified 450-fold as a marker of urate oxidase [EC 1.7.3.3.] activity. This preparation has a high specific activity of urate oxidase but not of other peroxisomal enzymes: D-amino acid oxidase [EC 1.4.3.3.], L-alpha-hydroxy acid oxidase [EC 1.1.3.15], or catalase [EC 1.11.1.6]. No activity of marker enzymes for other subcellular particles; cytochrome c oxidase [EC1.9.3.1] (mitochondria), acid phosphatase [EC 3.1.3.2] (lysosomes), or glucose-6-phosphatase [EC 3.1.3.9] (microsomes), was detected in this preparation. The core obtained showed a single protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the position of the band was found to correspond to a molecular weight 35,000. When the peroxisomal core was subjected to treatment at various pH's with 0.1 M carbonate buffer, urate oxidase was almost completely solubulized at pH 11.0, although approximately 35% of the core protein still remained in the pellet After solubilization of the core at pH 11.0, the specific activity of urate oxidase in the supernatant increased about 1.6 times; the density of the insoluble protein remaining in the pellet was identical with the that of the original core on sucrose density gradient centrifugation."}
{"id": "PMID:8434", "title": "Depolarization-induced calcium release from sarcoplasmic reticulum fragments. I. Release of calcium taken up upon using ATP.", "content": "Ca2& taken up by sarcoplasmic reticulum membrane fragments (SRF) upon using ATP could be released rapidly by changing the anion outside the vesicles from methanesulfonate to chloride. It is considered that this anion exchange caused depolarization of the sarcoplasmic reticulum membrane. Similar rapid release of Ca2& taken up by SRF was also caused by a change from high to low osmotic pressure, probably due to bursting of the membrane. On the basis of experiments in which these two types of Ca2& release were discriminated, it was concluded that Ca2& bound inside the membrane was released directly by anion exchange (depolarization). However, Ca2& release was not caused by cation exchange. Sucrose inhibited these two types of Ca2& release. Cia2& taken up in the presence of oxalate could not be released by any treatment used. Liver microsome fraction also has Ca2& uptake activity. However, Ca2& was not released upon anion exchange, but was released upon oxmotic change. These results show that Ca2& release from SRF upon anion exchange is specific to the sarcoplasmic reticulum membrane. In conclusion, SRF membrane retains the ability to respond to the depolarization caused by ion exchange and can release the accumulated Ca2&.", "contents": "Depolarization-induced calcium release from sarcoplasmic reticulum fragments. I. Release of calcium taken up upon using ATP. Ca2& taken up by sarcoplasmic reticulum membrane fragments (SRF) upon using ATP could be released rapidly by changing the anion outside the vesicles from methanesulfonate to chloride. It is considered that this anion exchange caused depolarization of the sarcoplasmic reticulum membrane. Similar rapid release of Ca2& taken up by SRF was also caused by a change from high to low osmotic pressure, probably due to bursting of the membrane. On the basis of experiments in which these two types of Ca2& release were discriminated, it was concluded that Ca2& bound inside the membrane was released directly by anion exchange (depolarization). However, Ca2& release was not caused by cation exchange. Sucrose inhibited these two types of Ca2& release. Cia2& taken up in the presence of oxalate could not be released by any treatment used. Liver microsome fraction also has Ca2& uptake activity. However, Ca2& was not released upon anion exchange, but was released upon oxmotic change. These results show that Ca2& release from SRF upon anion exchange is specific to the sarcoplasmic reticulum membrane. In conclusion, SRF membrane retains the ability to respond to the depolarization caused by ion exchange and can release the accumulated Ca2&."}
{"id": "PMID:8435", "title": "Depolarization-induced calcium release from sarcoplasmic reticulum fragments. II. Release of calcium incorporated with ATP.", "content": "Ca2& incorporated in vesicles of sarcoplasmic reticulum fragments (SRF) by diffusion could be released rapidly by changing the ionic environment, by dilution from methanesulfonate (MS) to chloride. This ion exchange is considered to make the membrane potential of SRF inside-negative. Much faster release of Ca2t was also observed upon osmotic change from high to low. These responses were very similar to the Ca2& release from SRF after take up using ATP, but the release rate was slow in the case of anion exchnage. The behavior of K&, Na&, sucrose, and inulin incorporated in SRF was followed upon similar treatment. These ions and nolecules were not released upon ion exchange, but were immediately released by osomtic treatment. Therefore, the Ca& release upon anion exchange was not due to the bursting of SRF, but to a direct effect such as a membrane potential change of the SRF. The behavior of anion such as C1- and propionate could not followed by the same method because of the large permability of these anions. It was also shown that Ca& release upon ion exchange was not a direct effect of pH change. Liver microsomes did not show Ca& release upon the same treatment as SRF.", "contents": "Depolarization-induced calcium release from sarcoplasmic reticulum fragments. II. Release of calcium incorporated with ATP. Ca2& incorporated in vesicles of sarcoplasmic reticulum fragments (SRF) by diffusion could be released rapidly by changing the ionic environment, by dilution from methanesulfonate (MS) to chloride. This ion exchange is considered to make the membrane potential of SRF inside-negative. Much faster release of Ca2t was also observed upon osmotic change from high to low. These responses were very similar to the Ca2& release from SRF after take up using ATP, but the release rate was slow in the case of anion exchnage. The behavior of K&, Na&, sucrose, and inulin incorporated in SRF was followed upon similar treatment. These ions and nolecules were not released upon ion exchange, but were immediately released by osomtic treatment. Therefore, the Ca& release upon anion exchange was not due to the bursting of SRF, but to a direct effect such as a membrane potential change of the SRF. The behavior of anion such as C1- and propionate could not followed by the same method because of the large permability of these anions. It was also shown that Ca& release upon ion exchange was not a direct effect of pH change. Liver microsomes did not show Ca& release upon the same treatment as SRF."}
{"id": "PMID:8436", "title": "Partial proteolysis of some cellulase components from Trichoderma viride and the substrate specificity of the modified products.", "content": "An endo-cellulase component [EC 3.2.1.4] or random type, F II, was obtained from \"Cellulase Onozuka,\" a commercial product from Trichoderma viride, and was subjected to partial proteolysiats with a protease preparation of the same fungal origin. The resulting modified cellulase was fractioned by two steps of column chromatography, and the resulting patterns, together with the substrate specificity expressed in terms of the randomness of CMC hydrolysis and the immunological properties against anti-F II-rabbit se-um, were examined. The chromatographic patterns were very similar to those of cellulase subfractions without proteolytic treatment. Moreover, the immunological response of the modified cellulases from F II was mostly positive and their randomness of CMC hydrolysis was generally lower, compared with subfractions of F II which were not subjected to proteolysis. The subfractions of Peak III, which were obtained from F II by proteolysis, showed mostly negative immunological response and higher randomness of CMC hydrolysis compared with subfractions of Peak III which were not subjected to proteolysis. Thus, some limited proteolysis of cellulase components may, at least in part, be responsible for its multiplicity in vivo.", "contents": "Partial proteolysis of some cellulase components from Trichoderma viride and the substrate specificity of the modified products. An endo-cellulase component [EC 3.2.1.4] or random type, F II, was obtained from \"Cellulase Onozuka,\" a commercial product from Trichoderma viride, and was subjected to partial proteolysiats with a protease preparation of the same fungal origin. The resulting modified cellulase was fractioned by two steps of column chromatography, and the resulting patterns, together with the substrate specificity expressed in terms of the randomness of CMC hydrolysis and the immunological properties against anti-F II-rabbit se-um, were examined. The chromatographic patterns were very similar to those of cellulase subfractions without proteolytic treatment. Moreover, the immunological response of the modified cellulases from F II was mostly positive and their randomness of CMC hydrolysis was generally lower, compared with subfractions of F II which were not subjected to proteolysis. The subfractions of Peak III, which were obtained from F II by proteolysis, showed mostly negative immunological response and higher randomness of CMC hydrolysis compared with subfractions of Peak III which were not subjected to proteolysis. Thus, some limited proteolysis of cellulase components may, at least in part, be responsible for its multiplicity in vivo."}
{"id": "PMID:8437", "title": "Purification and properties of an endo-cellulase of avicelase type from Irpex lacteus (Polyporus tulipiferae).", "content": "A culture filtrate of Irpex lacteus (Polyporus tulipiferae) was fractionated initially by salting out with ammonium sulfate, and a cellulase [EC 3.2.1.4.] fraction with high Avicel-hydrolyzing activity (formerly called Avicelase) was extensively purified by a series of column chromatography procedures. This purified endo-cellulase showed a less random hydrolytic mechanism, and was obtained in a yield of 0.04% with respect to the starting material. Its specific activity was enhanced approximately 30 times over that of the starting material. The cellulase component showed a single peak on both ultracentrifugal and acrylamide disc electrophoretic analyses. Its molecular weight was estimated to be 56,000. It contained 12.2% carbohydrate; the major sugar constituents were glucose and mannose. Regarding the amino acid composition, the contents of aspartic acid and glycine were highest, followed by those of glutamic acid, serine, and theonine. The cellulase component was not markedly inhibited by most metal ions tested excepted for Hg2+. This purified endo-cellulase attacked a series of cellooligosaccharides, beta-cellobioside, CM-cellulose, and insoluble, cellulosic substrates. In the digests from insoluble substrates, glucose, cellobiose, cellotriose, and cellotetraose were detectable, but the amount of cellobiose was the largest by far. In constrast, cellobiose and glucose were produced in almost equal amounts from beta-cellobioside.", "contents": "Purification and properties of an endo-cellulase of avicelase type from Irpex lacteus (Polyporus tulipiferae). A culture filtrate of Irpex lacteus (Polyporus tulipiferae) was fractionated initially by salting out with ammonium sulfate, and a cellulase [EC 3.2.1.4.] fraction with high Avicel-hydrolyzing activity (formerly called Avicelase) was extensively purified by a series of column chromatography procedures. This purified endo-cellulase showed a less random hydrolytic mechanism, and was obtained in a yield of 0.04% with respect to the starting material. Its specific activity was enhanced approximately 30 times over that of the starting material. The cellulase component showed a single peak on both ultracentrifugal and acrylamide disc electrophoretic analyses. Its molecular weight was estimated to be 56,000. It contained 12.2% carbohydrate; the major sugar constituents were glucose and mannose. Regarding the amino acid composition, the contents of aspartic acid and glycine were highest, followed by those of glutamic acid, serine, and theonine. The cellulase component was not markedly inhibited by most metal ions tested excepted for Hg2+. This purified endo-cellulase attacked a series of cellooligosaccharides, beta-cellobioside, CM-cellulose, and insoluble, cellulosic substrates. In the digests from insoluble substrates, glucose, cellobiose, cellotriose, and cellotetraose were detectable, but the amount of cellobiose was the largest by far. In constrast, cellobiose and glucose were produced in almost equal amounts from beta-cellobioside."}
{"id": "PMID:8438", "title": "Xylanase activity of an endo-cellulase of carboxymethyl-cellulase type from Irpex lacteus (Polyporus tulipiferae).", "content": "An endo-cellulase [EC 3.2.1.4.] of carboxymethyl-cellulase type (F-1) which was fractionated from culture filtrate of Irpex lacetus and purified to electrophoretic and ultracentrifugal homogeneity, was found to show xylanase [EC 3.2.1.8.] activity. The activity was not removed from any of the intermediate fractions during the purification of the initial F-I peak, and the radio of xylanase to cellulase activity remained almost unchanged through the purification processes. The xylanase activity of F-I showed not only the same optiomal pH, heat stability, and pH stability as its cellulase activity, but also the same mobility as the cellulase activity upon cellulose acetate film and starch zone electrophoreses. The overall rates of hydrolysis of mixtures of variouis concentrations of CM-cellulose and xylan by F-1 coincided well with those calculated from the Michaelis-Menten treatment of two substances competing for the same active site of the enzyme. These results indicate that the xylanase activity of F-1 is intrinsic to the cellulase itself.", "contents": "Xylanase activity of an endo-cellulase of carboxymethyl-cellulase type from Irpex lacteus (Polyporus tulipiferae). An endo-cellulase [EC 3.2.1.4.] of carboxymethyl-cellulase type (F-1) which was fractionated from culture filtrate of Irpex lacetus and purified to electrophoretic and ultracentrifugal homogeneity, was found to show xylanase [EC 3.2.1.8.] activity. The activity was not removed from any of the intermediate fractions during the purification of the initial F-I peak, and the radio of xylanase to cellulase activity remained almost unchanged through the purification processes. The xylanase activity of F-I showed not only the same optiomal pH, heat stability, and pH stability as its cellulase activity, but also the same mobility as the cellulase activity upon cellulose acetate film and starch zone electrophoreses. The overall rates of hydrolysis of mixtures of variouis concentrations of CM-cellulose and xylan by F-1 coincided well with those calculated from the Michaelis-Menten treatment of two substances competing for the same active site of the enzyme. These results indicate that the xylanase activity of F-1 is intrinsic to the cellulase itself."}
{"id": "PMID:8439", "title": "Active transport of alanine by thermostable membrane vesicles isolated from a thermophilic bacterium.", "content": "1. Thermostable membrane vesicles which were capable of active transport of alanine dependent on either respiration or an artificial membrane potential were isolated from the thermophilic aerobic bacterium PS3. 2. Uptake of alanine was dependent on the oxidation of ascorbate-phenazine methosulfate or on generated or exogenous NADH, but succinate and malate failed to drive the uptake. The optimum temperature for respiration-driven uptake of alanine was 45 to 60 degrees. 3. Potassium ion-loaded vesicles were prepared by incubating vesicles at 55 degrees in 0.5 M potassium phosphate. The addition of valinomycin elicited rapid and transient uptake of alanine under the test conditions. Uptake of alanine in response to valinomycin was progressively enhanced by the addition of dicylohexylcarbodiimide, but was completely abolished in the presence of a proton conductor or synthetic permeable cation. The effect of dicyclohexylcarbodiimide was dependent on its concentration and was maximal at a concentration of 0.4 mM. 4. The proton permeability of membrane vesicles was reduced by the addition of dicyclohexylcarbodiimide. A small but significant difference was found in the initial rates of proton uptake in the presence of dicyclohexylcarbodiimide with and without alanine. The results suggest that protons alanine are transported simultaneously in a stoichiometric ratio of 1 : 1. 5. The uptake of alanine was also driven by a pH gradient induced by an instantaneous pH drop in a suspension of alkali-loaded vesicles. Thus, alanine accumulation was driven not only by an electrical potential but also by a pH gradient. 6. Addition of ATP resulted in the inhibition of alanine uptake dependent on artificial membrane potential. ATP hydrolysis by membrane ATPase created a membrane potential which was inside-positive, and this might decrease the effective membrane potential (generated by K+ efflux mediated by valinomycin) available to drive alanine uptake.", "contents": "Active transport of alanine by thermostable membrane vesicles isolated from a thermophilic bacterium. 1. Thermostable membrane vesicles which were capable of active transport of alanine dependent on either respiration or an artificial membrane potential were isolated from the thermophilic aerobic bacterium PS3. 2. Uptake of alanine was dependent on the oxidation of ascorbate-phenazine methosulfate or on generated or exogenous NADH, but succinate and malate failed to drive the uptake. The optimum temperature for respiration-driven uptake of alanine was 45 to 60 degrees. 3. Potassium ion-loaded vesicles were prepared by incubating vesicles at 55 degrees in 0.5 M potassium phosphate. The addition of valinomycin elicited rapid and transient uptake of alanine under the test conditions. Uptake of alanine in response to valinomycin was progressively enhanced by the addition of dicylohexylcarbodiimide, but was completely abolished in the presence of a proton conductor or synthetic permeable cation. The effect of dicyclohexylcarbodiimide was dependent on its concentration and was maximal at a concentration of 0.4 mM. 4. The proton permeability of membrane vesicles was reduced by the addition of dicyclohexylcarbodiimide. A small but significant difference was found in the initial rates of proton uptake in the presence of dicyclohexylcarbodiimide with and without alanine. The results suggest that protons alanine are transported simultaneously in a stoichiometric ratio of 1 : 1. 5. The uptake of alanine was also driven by a pH gradient induced by an instantaneous pH drop in a suspension of alkali-loaded vesicles. Thus, alanine accumulation was driven not only by an electrical potential but also by a pH gradient. 6. Addition of ATP resulted in the inhibition of alanine uptake dependent on artificial membrane potential. ATP hydrolysis by membrane ATPase created a membrane potential which was inside-positive, and this might decrease the effective membrane potential (generated by K+ efflux mediated by valinomycin) available to drive alanine uptake."}
{"id": "PMID:8440", "title": "Purification and characterization of methioninase from Pseudomonas putida.", "content": "Methioninase of Pseudomonas putida was purified to homogeneity, as judged by polyacrylamide gel electrophoresis, with a specific activity 270-fold higher than that of the crude extract. 1. The purified enzyme had an S20,w of 8.37, a molecular weight of 160,000, and an isoelectric point of 5.6. 2. A break in the Arrhenius plot was observed at 40 degrees and the activation energies below and above this temperature were 15.5 and 2.97 kcal per mole, respectively. 3. In addition to L-methionine, various S-substituted derivatives of homocysteine and cysteine could serve as substrates. D-Methionine, 2-oxo-4-methylthiobutanoate, and related non sulfur-containing amino acids were inert. Equimolar formation of alpha-ketobutyrate and CH3SH was observed with methionine as a substrate. 4. In addition to the protein peak at 278 nm, two absorption maxima were observed at 345 and 430 nm at pH 7.5. Hydroxylamine removed the enzyme-bound pyridoxal phosphate, resulting in almost complete resolution with the concomitant disappearance of both peaks. Reconstruction of the treated enzyme could be achieved by addition of the cofactor; the Km value was calculated to be 0.37 muM. 5. The reported purified enzyme should be designated as L-methionine methanethiollyase (deaminating).", "contents": "Purification and characterization of methioninase from Pseudomonas putida. Methioninase of Pseudomonas putida was purified to homogeneity, as judged by polyacrylamide gel electrophoresis, with a specific activity 270-fold higher than that of the crude extract. 1. The purified enzyme had an S20,w of 8.37, a molecular weight of 160,000, and an isoelectric point of 5.6. 2. A break in the Arrhenius plot was observed at 40 degrees and the activation energies below and above this temperature were 15.5 and 2.97 kcal per mole, respectively. 3. In addition to L-methionine, various S-substituted derivatives of homocysteine and cysteine could serve as substrates. D-Methionine, 2-oxo-4-methylthiobutanoate, and related non sulfur-containing amino acids were inert. Equimolar formation of alpha-ketobutyrate and CH3SH was observed with methionine as a substrate. 4. In addition to the protein peak at 278 nm, two absorption maxima were observed at 345 and 430 nm at pH 7.5. Hydroxylamine removed the enzyme-bound pyridoxal phosphate, resulting in almost complete resolution with the concomitant disappearance of both peaks. Reconstruction of the treated enzyme could be achieved by addition of the cofactor; the Km value was calculated to be 0.37 muM. 5. The reported purified enzyme should be designated as L-methionine methanethiollyase (deaminating)."}
{"id": "PMID:8441", "title": "Purification and properties of the extracellular dextransucrase from Leuconostoc mesenteroides NRRL B-1299.", "content": "Dextransucrase [EC 2.4.1.5] activity from cell-free culture supernatant of Leuconostoc mesenteroides NRRL B-1299 was purified by (NH4)2SO4 fractionation, adsorption on hydroxyapatite, chromatography on DEAE-cellulose and gel filtration on Sephadex G-75. The extracellular enzyme was separated into two principal forms, enzymes I and N, and the latter was shown to be an aggregated form of the protomer, enzyme I. Enzymes I and N were both electrophoretically homogeneous and their relative activities reached 820 and 647 times that of the culture supernatant, respectively. On sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis, enzyme N dissociated into the protomer enzyme I, with a molecular weight of 48,000. Enzyme I was gradually converted into enzyme N upon aging, and this conversion was stimulated in the presence of NaCl. The optimum pH and temperature of enzyme I activity were pH 6.0 and 40 degrees, respectively, while those of enzyme N were pH 5.5 and 35 degrees. The Km values of enzymes I and N were 13.9 and 13.1 mM, respectively. Ca2+, Mg2+, Fe2+, and Co2+ stimulated the activity of enzyme N, and EDTA showed a potent inhibitory effect on this enzyme. Moreover, the activity of enzyme N was more effectively stimulated by exogenous dextrans as compared with enzyme I.", "contents": "Purification and properties of the extracellular dextransucrase from Leuconostoc mesenteroides NRRL B-1299. Dextransucrase [EC 2.4.1.5] activity from cell-free culture supernatant of Leuconostoc mesenteroides NRRL B-1299 was purified by (NH4)2SO4 fractionation, adsorption on hydroxyapatite, chromatography on DEAE-cellulose and gel filtration on Sephadex G-75. The extracellular enzyme was separated into two principal forms, enzymes I and N, and the latter was shown to be an aggregated form of the protomer, enzyme I. Enzymes I and N were both electrophoretically homogeneous and their relative activities reached 820 and 647 times that of the culture supernatant, respectively. On sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis, enzyme N dissociated into the protomer enzyme I, with a molecular weight of 48,000. Enzyme I was gradually converted into enzyme N upon aging, and this conversion was stimulated in the presence of NaCl. The optimum pH and temperature of enzyme I activity were pH 6.0 and 40 degrees, respectively, while those of enzyme N were pH 5.5 and 35 degrees. The Km values of enzymes I and N were 13.9 and 13.1 mM, respectively. Ca2+, Mg2+, Fe2+, and Co2+ stimulated the activity of enzyme N, and EDTA showed a potent inhibitory effect on this enzyme. Moreover, the activity of enzyme N was more effectively stimulated by exogenous dextrans as compared with enzyme I."}
{"id": "PMID:8442", "title": "Estimation of tryptophyl and tyrosyl exposure in tryptophan-rich proteins by ultraviolet difference spectrophotometry. Lysozyme and Chymotrypsinogen.", "content": "Ultraviolet difference absorption spectra produced by ethylene glycol were measured for hen lysozyme [EC 3.2.1.17] and bovine chymotrypsinogen. N-Acetyl-L-tryptophanamide and N-acetyl-L-tyrosinamide were employed as model compounds for tryptophyl and tyrosyl residues, respectively, and their ultraviolet difference spectra were also measured as a function of ethylene glycol concentration. By comparison of the slopes of plots of molar difference extinction coefficients (delta epsilon) versus ethylene glycol concentration for the proteins with those of the model compounds at peak positions (291-293 and 284-287 nm) in the difference spectra, the average number of tyrosyl as well as tryptophyl residues in exposed states could be estimated. The results gave 2.7 tryptophyl and 1.9 tyrosyl residues exposed for lysozyme at pH 2.1 and 2.6 tryptophyl and 3.4 tyrosyl residues exposed for chymotrypsinogen at pH 5.4. The somewhat higher tyrosyl exposure of chymotrypsinogen, compared with the findings from spectrophotometric titration and chemical modification, was not unexpected, because delta epsilon285 was larger than delta epsilon292, and the situation is discussed with reference to preferential interaction of ethylene glycol with the tyrosyl residues and/or side chains in the vicinity of the chromophore in the protein. The procedure employed in the present work seems to be suitable for estimation of the average number of exposed tryptophyl and tyrosyl residues in tryptophan-rich proteins. The effects of ethylene glycol on the circular dichroism spectra of lysozyme at pH 2.1 and chymotrypsinogen at pH 5.4 were also investigated. At high ethylene glycol concentrations, both proteins were found to undergo conformational changes in the direction of more ordered structures, presumably more helical for lysozyme and more beta-structured for chymotrypsinogen.", "contents": "Estimation of tryptophyl and tyrosyl exposure in tryptophan-rich proteins by ultraviolet difference spectrophotometry. Lysozyme and Chymotrypsinogen. Ultraviolet difference absorption spectra produced by ethylene glycol were measured for hen lysozyme [EC 3.2.1.17] and bovine chymotrypsinogen. N-Acetyl-L-tryptophanamide and N-acetyl-L-tyrosinamide were employed as model compounds for tryptophyl and tyrosyl residues, respectively, and their ultraviolet difference spectra were also measured as a function of ethylene glycol concentration. By comparison of the slopes of plots of molar difference extinction coefficients (delta epsilon) versus ethylene glycol concentration for the proteins with those of the model compounds at peak positions (291-293 and 284-287 nm) in the difference spectra, the average number of tyrosyl as well as tryptophyl residues in exposed states could be estimated. The results gave 2.7 tryptophyl and 1.9 tyrosyl residues exposed for lysozyme at pH 2.1 and 2.6 tryptophyl and 3.4 tyrosyl residues exposed for chymotrypsinogen at pH 5.4. The somewhat higher tyrosyl exposure of chymotrypsinogen, compared with the findings from spectrophotometric titration and chemical modification, was not unexpected, because delta epsilon285 was larger than delta epsilon292, and the situation is discussed with reference to preferential interaction of ethylene glycol with the tyrosyl residues and/or side chains in the vicinity of the chromophore in the protein. The procedure employed in the present work seems to be suitable for estimation of the average number of exposed tryptophyl and tyrosyl residues in tryptophan-rich proteins. The effects of ethylene glycol on the circular dichroism spectra of lysozyme at pH 2.1 and chymotrypsinogen at pH 5.4 were also investigated. At high ethylene glycol concentrations, both proteins were found to undergo conformational changes in the direction of more ordered structures, presumably more helical for lysozyme and more beta-structured for chymotrypsinogen."}
{"id": "PMID:8443", "title": "Purification, crystallization, and some properties of creatine amidinohydrolase from Pseudomonas putida.", "content": "A method was developed for purification and crystallization of creatinase [creatine amidinohydrolase, EC 3.5.3.3] from Pseudomonas putida var. naraensis C-83. The purified preparation appeared homogeneous on disc electrophoresis and ultracentrifugation and had a molecular weight of 94,000. It was most active at pH 8 and stable between pH 6 and 8 for 24 hr at 37 degrees. SDS-polyacrylamide gel electrophoresis indicated that the native enzyme was made up of two subunit monomers, the molecular weights of which were estimated to be 47,000. Inhibition experiments suggested that a sulfhydryl group is located in or near the active site of the enzyme.", "contents": "Purification, crystallization, and some properties of creatine amidinohydrolase from Pseudomonas putida. A method was developed for purification and crystallization of creatinase [creatine amidinohydrolase, EC 3.5.3.3] from Pseudomonas putida var. naraensis C-83. The purified preparation appeared homogeneous on disc electrophoresis and ultracentrifugation and had a molecular weight of 94,000. It was most active at pH 8 and stable between pH 6 and 8 for 24 hr at 37 degrees. SDS-polyacrylamide gel electrophoresis indicated that the native enzyme was made up of two subunit monomers, the molecular weights of which were estimated to be 47,000. Inhibition experiments suggested that a sulfhydryl group is located in or near the active site of the enzyme."}
{"id": "PMID:8444", "title": "Charge transfer mediated by nigericin in black lipid membranes.", "content": "Nigericin, in the concentration range (10(-6) M or higher) at which it uncouples intact mitochondria, was found to increase the conductance of black lipid membranes (BLM) by several orders of magnitude. The dependence of the membrane conductance on pH and K+ concentration suggests a mechanism for the transfer of charge mediated by this ionophore based on a mobile dimer with both nigericin molecules protonated and complexed with one K+. This charged complex accounts for the uncoupling effect observed in intact mitochondria.", "contents": "Charge transfer mediated by nigericin in black lipid membranes. Nigericin, in the concentration range (10(-6) M or higher) at which it uncouples intact mitochondria, was found to increase the conductance of black lipid membranes (BLM) by several orders of magnitude. The dependence of the membrane conductance on pH and K+ concentration suggests a mechanism for the transfer of charge mediated by this ionophore based on a mobile dimer with both nigericin molecules protonated and complexed with one K+. This charged complex accounts for the uncoupling effect observed in intact mitochondria."}
{"id": "PMID:8445", "title": "Influence of surface potentials on the mitochondrial H+ pump and on lipid-phase transitions.", "content": "It has been shown that the surface potential of lipid membranes, as well as of mitochondria, can be shifted more positive by absorption of alkylbiguanides. Both phospholipid vesicles and natural membranes respond in an analogous way to this shift. Ion activities at the immediate membrane surface are influenced by sign and magnitude of the surface charge. Corresponding effects on ion transport and on fluorescence-probe binding can be observed. The mitochondrial H+ pump is inhibited when the surface charge is shifted more positive. In contrast,the absolute charge density determines the temperature of the ordered-fluid transition. The latter is increased by biguanides, suggesting that the membrane is rendered more rigid. The experiments make obvious that physical relations derived from model systems apply equally well to lipid-containing natural membranes.", "contents": "Influence of surface potentials on the mitochondrial H+ pump and on lipid-phase transitions. It has been shown that the surface potential of lipid membranes, as well as of mitochondria, can be shifted more positive by absorption of alkylbiguanides. Both phospholipid vesicles and natural membranes respond in an analogous way to this shift. Ion activities at the immediate membrane surface are influenced by sign and magnitude of the surface charge. Corresponding effects on ion transport and on fluorescence-probe binding can be observed. The mitochondrial H+ pump is inhibited when the surface charge is shifted more positive. In contrast,the absolute charge density determines the temperature of the ordered-fluid transition. The latter is increased by biguanides, suggesting that the membrane is rendered more rigid. The experiments make obvious that physical relations derived from model systems apply equally well to lipid-containing natural membranes."}
{"id": "PMID:8446", "title": "Evidence for multiple sites of ferricyanide reduction in chloroplasts.", "content": "Various sites of ferricyanide reduction were studied in spinach chloroplasts. It was found that in the presence of dibromothymoquinone a fraction of ferricyanide reduction was dibromothymoquinone sensitive, implying that ferricyanide can be reduced by photosystem I as well as photosystem II. To separate ferricyanide reduction sites in photosystem II, orthophenanthroline and dichlorophenyl dimethylurea inhibitions were compared at various pHs. It was noted that at low pH ferricyanide reduction was not completely inhibited by orothophenanthroline. At high pH's, however, inhibition of ferricyanide reduction by orthophenanthroline was complete. It was found that varying concentration of orthophenanthroline at a constant pH showed different degrees of inhibition. In the study of ferricyanide reduction by photosystem II various treatments affecting plastocyanin were performed. It was found that Tween-20 or KCN treatments which inactivated plastocyanin did not completely inactivate ferricyanide reduction. These data support the conclusion that ferricyanide accepts electrons both before and after plastoquinone in photosystem II.", "contents": "Evidence for multiple sites of ferricyanide reduction in chloroplasts. Various sites of ferricyanide reduction were studied in spinach chloroplasts. It was found that in the presence of dibromothymoquinone a fraction of ferricyanide reduction was dibromothymoquinone sensitive, implying that ferricyanide can be reduced by photosystem I as well as photosystem II. To separate ferricyanide reduction sites in photosystem II, orthophenanthroline and dichlorophenyl dimethylurea inhibitions were compared at various pHs. It was noted that at low pH ferricyanide reduction was not completely inhibited by orothophenanthroline. At high pH's, however, inhibition of ferricyanide reduction by orthophenanthroline was complete. It was found that varying concentration of orthophenanthroline at a constant pH showed different degrees of inhibition. In the study of ferricyanide reduction by photosystem II various treatments affecting plastocyanin were performed. It was found that Tween-20 or KCN treatments which inactivated plastocyanin did not completely inactivate ferricyanide reduction. These data support the conclusion that ferricyanide accepts electrons both before and after plastoquinone in photosystem II."}
{"id": "PMID:8447", "title": "Rates of phosphorylation and dephosphorylation of phosphoglycerate mutase and bisphosphoglycerate synthase.", "content": "Phosphoglycerate mutase and bisphosphoglycerate synthase (mutase) can both be phosphorylated by either glycerate-1,3-P2 or glycerate-2,3-P2 to form phosphohistidine enzymes. The present study uses a rapid quench procedure to determine if, for each enzyme, the formation of the phosphorylated enzyme and phosphate transfer from the enzyme can occur at rates consistent with the overall reactions. With bisphosphoglycerate synthase from horse red blood cells (glycerate-1,3-P2 leads to glycerate-2,3-P2) at pH 7.5, 25 degrees, phosphorylation of the enzyme appears rate-limiting, k = 13.5 s-1, compared with kcat = 12.5 s-1 for the overall synthase rate. Phosphoryl transfer from the enzyme to phosphoglycerate occurs at 38 s-1 at 4 degrees and was too fast to measure at 25 degrees. With chicken muscle phosphoglycerate mutase the half-times were too short to measure under optimal conditions. The rate of enzyme phosphorylation by glycerate-2,3-P2 at pH 5.5, 4 degrees, could account for the overall reaction rate of 170 s-1. The rate of phosphoryl transfer from the enzyme to glycerate-3-P was too rapid to measure under the same conditions. It is concluded that the phosphorylated enzymes have kinetic properties consistent with their participation as intermediates in the reactions catalyzed by these enzymes.", "contents": "Rates of phosphorylation and dephosphorylation of phosphoglycerate mutase and bisphosphoglycerate synthase. Phosphoglycerate mutase and bisphosphoglycerate synthase (mutase) can both be phosphorylated by either glycerate-1,3-P2 or glycerate-2,3-P2 to form phosphohistidine enzymes. The present study uses a rapid quench procedure to determine if, for each enzyme, the formation of the phosphorylated enzyme and phosphate transfer from the enzyme can occur at rates consistent with the overall reactions. With bisphosphoglycerate synthase from horse red blood cells (glycerate-1,3-P2 leads to glycerate-2,3-P2) at pH 7.5, 25 degrees, phosphorylation of the enzyme appears rate-limiting, k = 13.5 s-1, compared with kcat = 12.5 s-1 for the overall synthase rate. Phosphoryl transfer from the enzyme to phosphoglycerate occurs at 38 s-1 at 4 degrees and was too fast to measure at 25 degrees. With chicken muscle phosphoglycerate mutase the half-times were too short to measure under optimal conditions. The rate of enzyme phosphorylation by glycerate-2,3-P2 at pH 5.5, 4 degrees, could account for the overall reaction rate of 170 s-1. The rate of phosphoryl transfer from the enzyme to glycerate-3-P was too rapid to measure under the same conditions. It is concluded that the phosphorylated enzymes have kinetic properties consistent with their participation as intermediates in the reactions catalyzed by these enzymes."}
{"id": "PMID:8448", "title": "5-Iodo-5'-amino-2',5'-dideoxyuridine-5'-N'-triphosphate. Synthesis, chemical properties, and effect on Escherichia coli thymidine kinase activity.", "content": "5-Iodo-5'-amino-2',5'-dideoxyuridine-5'-N'-triphosphate (AIdUTP), a phosphoramidate analog of 5-iodo-2',5'-dideoxyuridine 5'-triphosphate (IdUTP), was synthesized and some of its chemical and biological properties were investigated. Although AIdUTP is stable in alkaline solutions, below pH 8 it undergoes degradation by a novel phosphorylysis reaction which exhibits first order kinetics. Inclusion of magnesium ion in the reaction mixture decreased the rate of degradation. Protonation of a group on AIdUTP which has a pKa of 6.10, presumably the secondary ionized oxygen on the gamma phosphate, precedes phosphorylysis. The only detectable reaction products are the nucleoside, 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd), and trimetaphosphate. A mechanism for the acid catalyzed phosphorylysis of AIdUTP is proposed. AIdUTP, like TTP, converts Escherichia coli thymidine kinase into an inactive dimer with a sedimentation coefficient of 5.78 S. AIdUTP is, however, 60-fold more potent as an allosteric inhibitor than is TTP at pH 7.8. Although the inhibitory effect of TTP is markedly reduced at high pH, the activity of AIdUTP is lowered only slightly. The allosteric effects of AIdUTP also differ from those of IdUTP, which is an inhibitor at low pH but a strong activator above pH 7.4. 5-Iodo-2'-deoxycytidine 5'-triphosphate, a potent enzyme activator, cannot completely reverse the AIdUTP inhibition, even when present at a 150-fold molar excess.", "contents": "5-Iodo-5'-amino-2',5'-dideoxyuridine-5'-N'-triphosphate. Synthesis, chemical properties, and effect on Escherichia coli thymidine kinase activity. 5-Iodo-5'-amino-2',5'-dideoxyuridine-5'-N'-triphosphate (AIdUTP), a phosphoramidate analog of 5-iodo-2',5'-dideoxyuridine 5'-triphosphate (IdUTP), was synthesized and some of its chemical and biological properties were investigated. Although AIdUTP is stable in alkaline solutions, below pH 8 it undergoes degradation by a novel phosphorylysis reaction which exhibits first order kinetics. Inclusion of magnesium ion in the reaction mixture decreased the rate of degradation. Protonation of a group on AIdUTP which has a pKa of 6.10, presumably the secondary ionized oxygen on the gamma phosphate, precedes phosphorylysis. The only detectable reaction products are the nucleoside, 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd), and trimetaphosphate. A mechanism for the acid catalyzed phosphorylysis of AIdUTP is proposed. AIdUTP, like TTP, converts Escherichia coli thymidine kinase into an inactive dimer with a sedimentation coefficient of 5.78 S. AIdUTP is, however, 60-fold more potent as an allosteric inhibitor than is TTP at pH 7.8. Although the inhibitory effect of TTP is markedly reduced at high pH, the activity of AIdUTP is lowered only slightly. The allosteric effects of AIdUTP also differ from those of IdUTP, which is an inhibitor at low pH but a strong activator above pH 7.4. 5-Iodo-2'-deoxycytidine 5'-triphosphate, a potent enzyme activator, cannot completely reverse the AIdUTP inhibition, even when present at a 150-fold molar excess."}
{"id": "PMID:8449", "title": "Purification, properties, and substrate specificities of phosphoprotein phosphatase(s) from rabbit liver.", "content": "The phosphoprotein phosphatase(s) acting on muscle phosphorylase a was purified from rabbit liver by acid precipitation, high speed centrifugation, chromatography on DEAE-Sephadex A-50, Sephadex G-75, and Sepharose-histone. Enzyme activity was recovered in the final step as two distinct peaks tentatively referred to as phosphoprotein phosphatases I and II. Each phosphatase showed a single broad band when examined by sodium dodecyl sulfate gel electrophoresis; the molecular weights derived by this method were approximately 30,500 for phosphoprotein phosphatase I and 34,000 for phosphoprotein phosphatase II. The s20, w value for each enzyme was 3.40. Using this value and values for the Stokes radii, the molecular weight for each enzyme was calculated to be 34,500. Both phosphatases, in addition to catalyzing the conversion of phosphorylase a to b, also catalyzed the dephosphorylation of glycogen synthase D, activated phosphorylase kinase, phosphorylated histone, phosphorylated casein, and the phosphorylated inhibitory component of troponin (TN-I). The relative activities of the phosphatases with respect to phosphorylase a, glycogen synthase D, histone, and casein remained essentially constant throughout the purification. The activities of both phosphatases with different substrates decreased in parallel when they were denatured by incubation at 55 degrees and 65 degrees. The Km values of phosphoprotein phosphatase I for phosphorylase a, histone, and casein were lower than the values obtained for phosphoprotein phosphatase II. With glycogen synthase D as substrate, each enzyme gave essentially the same Km value. Utilizing either enzyme, it was found that activity toward a given substrate was inhibited competitively by each of the alternative substrates. The results suggest that phosphoprotein phosphatases I and II are each active toward all of the substrates tested.", "contents": "Purification, properties, and substrate specificities of phosphoprotein phosphatase(s) from rabbit liver. The phosphoprotein phosphatase(s) acting on muscle phosphorylase a was purified from rabbit liver by acid precipitation, high speed centrifugation, chromatography on DEAE-Sephadex A-50, Sephadex G-75, and Sepharose-histone. Enzyme activity was recovered in the final step as two distinct peaks tentatively referred to as phosphoprotein phosphatases I and II. Each phosphatase showed a single broad band when examined by sodium dodecyl sulfate gel electrophoresis; the molecular weights derived by this method were approximately 30,500 for phosphoprotein phosphatase I and 34,000 for phosphoprotein phosphatase II. The s20, w value for each enzyme was 3.40. Using this value and values for the Stokes radii, the molecular weight for each enzyme was calculated to be 34,500. Both phosphatases, in addition to catalyzing the conversion of phosphorylase a to b, also catalyzed the dephosphorylation of glycogen synthase D, activated phosphorylase kinase, phosphorylated histone, phosphorylated casein, and the phosphorylated inhibitory component of troponin (TN-I). The relative activities of the phosphatases with respect to phosphorylase a, glycogen synthase D, histone, and casein remained essentially constant throughout the purification. The activities of both phosphatases with different substrates decreased in parallel when they were denatured by incubation at 55 degrees and 65 degrees. The Km values of phosphoprotein phosphatase I for phosphorylase a, histone, and casein were lower than the values obtained for phosphoprotein phosphatase II. With glycogen synthase D as substrate, each enzyme gave essentially the same Km value. Utilizing either enzyme, it was found that activity toward a given substrate was inhibited competitively by each of the alternative substrates. The results suggest that phosphoprotein phosphatases I and II are each active toward all of the substrates tested."}
{"id": "PMID:8450", "title": "Nucleophilic addition reactions of free and enzyme-bound deazaflavin.", "content": "DeazaFMN-containing glycolate oxidase has been prepared and shown to catalyze the stereospecific transfer of the alpha-hydrogen from substrate to enzyme-bound deazaFMN. The reaction of sulfite, cyanide, and hydroxylamine with several deazaflavin-containing enzymes (glycolate oxidase, D-amino acid oxidase, glucose oxidase, N-methylglutamate synthetase) and free deazaFMN has been examined. All the deazaflavin systems tested form reversible 1:1 complexes with sulfite and cyanide. The pH dependence of the reaction of free deazaFMN with cyanide indicates that cyanide anion is the reacting nucleophile. Hydroxylamine complexes are formed with deazaFMN glycolate oxidase and deazaFAD glucose oxidase. The effectiveness of the various nucleophilic reagents in complex formation decreases in the following order: sulfite greater than cyanide greater than hydroxylamine. The relative stability observed for the sulfite and cyanide complexes formed with various deazaflavin systems (glycolate oxidase greater than D-amino acid oxidase greater than free deazaFMN) follows the same trend observed for the stability of the sulfite complexes formed with the corresponding flavin system. A correlation is also observed between the reduction potential (E'o) of the deazaflavin system (glycolate oxidase (- 170 mV) greater than D-amino acid oxidase (-240 mV) greater than free deazaFMN (-178 mV) and the stability of the deazaflavin-nucleophile complexes. The following evidence indicates that deazaflavin systems are generally more susceptible toward nucleophilic attack than corresponding flavin system: (a) with the exception of glucose oxidase, the dissociation constants for the deazaflavin-sulfite complexes are at least 1 order of magnitude less than the corresponding flavin sulfite complexes; (b) the least reactive nucleophile, hydroxylamine, does not form a complex with any of the flavin systems. In the case of cyanide, a complex is formed only with native glycolate oxidase, which is the flavin-containing system most susceptible to attack by the more reactive sulfite. Formation of the various (deaza)flavin-nucleophile complexes is characterized by a bleaching of the longer wavelength absorption band of the chromophore and increases in absorption below the isosbestic point of the reaction in the near-ultraviolet region of the spectrum. These results are consistent with the formation of covalent adducts via attack of the various nucleophiles at position 5 of (deaza)flavin. The reaction with cyanide provides the first example of a reversible addition of carbanion to enzyme-bound (deaza)flavin.", "contents": "Nucleophilic addition reactions of free and enzyme-bound deazaflavin. DeazaFMN-containing glycolate oxidase has been prepared and shown to catalyze the stereospecific transfer of the alpha-hydrogen from substrate to enzyme-bound deazaFMN. The reaction of sulfite, cyanide, and hydroxylamine with several deazaflavin-containing enzymes (glycolate oxidase, D-amino acid oxidase, glucose oxidase, N-methylglutamate synthetase) and free deazaFMN has been examined. All the deazaflavin systems tested form reversible 1:1 complexes with sulfite and cyanide. The pH dependence of the reaction of free deazaFMN with cyanide indicates that cyanide anion is the reacting nucleophile. Hydroxylamine complexes are formed with deazaFMN glycolate oxidase and deazaFAD glucose oxidase. The effectiveness of the various nucleophilic reagents in complex formation decreases in the following order: sulfite greater than cyanide greater than hydroxylamine. The relative stability observed for the sulfite and cyanide complexes formed with various deazaflavin systems (glycolate oxidase greater than D-amino acid oxidase greater than free deazaFMN) follows the same trend observed for the stability of the sulfite complexes formed with the corresponding flavin system. A correlation is also observed between the reduction potential (E'o) of the deazaflavin system (glycolate oxidase (- 170 mV) greater than D-amino acid oxidase (-240 mV) greater than free deazaFMN (-178 mV) and the stability of the deazaflavin-nucleophile complexes. The following evidence indicates that deazaflavin systems are generally more susceptible toward nucleophilic attack than corresponding flavin system: (a) with the exception of glucose oxidase, the dissociation constants for the deazaflavin-sulfite complexes are at least 1 order of magnitude less than the corresponding flavin sulfite complexes; (b) the least reactive nucleophile, hydroxylamine, does not form a complex with any of the flavin systems. In the case of cyanide, a complex is formed only with native glycolate oxidase, which is the flavin-containing system most susceptible to attack by the more reactive sulfite. Formation of the various (deaza)flavin-nucleophile complexes is characterized by a bleaching of the longer wavelength absorption band of the chromophore and increases in absorption below the isosbestic point of the reaction in the near-ultraviolet region of the spectrum. These results are consistent with the formation of covalent adducts via attack of the various nucleophiles at position 5 of (deaza)flavin. The reaction with cyanide provides the first example of a reversible addition of carbanion to enzyme-bound (deaza)flavin."}
{"id": "PMID:8451", "title": "Formation and properties of retinylphosphate galactose.", "content": "Crude cell membrane fractions from a number of tissues can form acidic glycolipids. The formation of acidic galactose lipid and mannose lipid was greatly reduced in vitamin A deficiency, primarily in tissues known to be mucus-producing. Mouse mastocytoma tissue was active in forming acidic galactose lipids with UDP-galactose as substrate. One of the products was identified as retinylphosphate galactose. The synthetase reaction producing this compound exhibited an apparent pH optimum at 6.3. The presence of detergent and retinol stimulated the synthetase reaction, which exhibited an absolute requirement for Mn2+ or Mg2+. The synthetase reaction was readily reversible. Incubation of particulate enzyme with retinylphosphate galactose and UDP yielded UDP-galactose and a compound tentatively identified as retinylphosphate. The galactose lipid was isolated by column chromatography on DEAE-cellulose and silica gel. The retinylphosphate galactose was homogeneous when examined by thin layer chromatography. Mild acid hydrolysis of labeled retinylphosphate galactose yields [14C]galactose, whereas alkaline hydrolysis and hydrogenolysis produced [14C]galactose 1-phosphate. Retinylphosphate galactose bound to vitamin A-depleted, retinol-binding protein.", "contents": "Formation and properties of retinylphosphate galactose. Crude cell membrane fractions from a number of tissues can form acidic glycolipids. The formation of acidic galactose lipid and mannose lipid was greatly reduced in vitamin A deficiency, primarily in tissues known to be mucus-producing. Mouse mastocytoma tissue was active in forming acidic galactose lipids with UDP-galactose as substrate. One of the products was identified as retinylphosphate galactose. The synthetase reaction producing this compound exhibited an apparent pH optimum at 6.3. The presence of detergent and retinol stimulated the synthetase reaction, which exhibited an absolute requirement for Mn2+ or Mg2+. The synthetase reaction was readily reversible. Incubation of particulate enzyme with retinylphosphate galactose and UDP yielded UDP-galactose and a compound tentatively identified as retinylphosphate. The galactose lipid was isolated by column chromatography on DEAE-cellulose and silica gel. The retinylphosphate galactose was homogeneous when examined by thin layer chromatography. Mild acid hydrolysis of labeled retinylphosphate galactose yields [14C]galactose, whereas alkaline hydrolysis and hydrogenolysis produced [14C]galactose 1-phosphate. Retinylphosphate galactose bound to vitamin A-depleted, retinol-binding protein."}
{"id": "PMID:8452", "title": "The allosteric regulation of hexokinase C from amphibian liver.", "content": "A type C hexokinase (ATP:D-hexose-6-phosphotransferase EC 2.7.1.1) was partially purified from the liver of the frog Calyptocephalella caudiverbera. The enzyme is inhibited by glucose levels in the range of normal blood sugar concentrations. The extent of the inhibition by glucose depends on the concentration of ATP, being most marked between 1 and 5 mM ATP. Fructose, although a substrate, was not inhibitory of its own phosphorylation. The inhibitory effect of high glucose levels exhibited a strong, reversible pH dependence being most marked at pH 6.5. At pH 7.5 the inhibition by high glucose levels was a function of the enzyme concentration, the effect being stronger at high enzyme concentrations, whereas no inhibition was observed when assaying very diluted preparations. At all enzyme concentrations studied, high levels of glucose caused no inhibition at pH 8.5, whereas at pH 6.5 strong inhibition was always observed. Short times of photooxidation of hexokinase C as well as incubation with low concentrations of p-chloromercuribenzoate resulted in the loss of the inhibition by excess of glucose. Glucose-6-phosphate was found to be a strong inhibitor of hexokinase C but only at high glucose levels. The inhibitory effect of glucose-6-P follows sigmoidal kinetics at low (about 0.02 mM) glucose concentrations, the Hill coefficient being 2.3. The kinetics of the inhibition became hyperbolic at high (greater than 0.2 mM) glucose levels. These results suggest that the inhibition of hexokinase C by excess glucose is due to the interaction of glucose with a second, aldose-specific, regulatory site on the enzyme. The modification of the inhibitory effect by ATP, glucose-6-P, enzyme concentration, and pH, all of them at physiological levels, indicates a major role for hexokinase C in the regulation of glucose utilization by the liver.", "contents": "The allosteric regulation of hexokinase C from amphibian liver. A type C hexokinase (ATP:D-hexose-6-phosphotransferase EC 2.7.1.1) was partially purified from the liver of the frog Calyptocephalella caudiverbera. The enzyme is inhibited by glucose levels in the range of normal blood sugar concentrations. The extent of the inhibition by glucose depends on the concentration of ATP, being most marked between 1 and 5 mM ATP. Fructose, although a substrate, was not inhibitory of its own phosphorylation. The inhibitory effect of high glucose levels exhibited a strong, reversible pH dependence being most marked at pH 6.5. At pH 7.5 the inhibition by high glucose levels was a function of the enzyme concentration, the effect being stronger at high enzyme concentrations, whereas no inhibition was observed when assaying very diluted preparations. At all enzyme concentrations studied, high levels of glucose caused no inhibition at pH 8.5, whereas at pH 6.5 strong inhibition was always observed. Short times of photooxidation of hexokinase C as well as incubation with low concentrations of p-chloromercuribenzoate resulted in the loss of the inhibition by excess of glucose. Glucose-6-phosphate was found to be a strong inhibitor of hexokinase C but only at high glucose levels. The inhibitory effect of glucose-6-P follows sigmoidal kinetics at low (about 0.02 mM) glucose concentrations, the Hill coefficient being 2.3. The kinetics of the inhibition became hyperbolic at high (greater than 0.2 mM) glucose levels. These results suggest that the inhibition of hexokinase C by excess glucose is due to the interaction of glucose with a second, aldose-specific, regulatory site on the enzyme. The modification of the inhibitory effect by ATP, glucose-6-P, enzyme concentration, and pH, all of them at physiological levels, indicates a major role for hexokinase C in the regulation of glucose utilization by the liver."}
{"id": "PMID:8453", "title": "Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid.", "content": "The three purified proteins which are required for microsomal stearyl-CoA desaturation, NADH-cytochrome b5 reductase, cytochrome b5, and desaturase, have been combined with egg lecithin or dimyristyl lecithin vesicles to reconstruct a functional electron transport system capable of utilizing NADH and O2 in the desaturation of stearyl-CoA. Such preparations appear to consist of phospholipid vesicles which contain the three proteins bound to the outer surface of the vesicles. Acyl-CoA derivatives containing 12 to 19 carbon fatty acyl chains are required for desaturase activity while derivatives containing 9 to 20 carbons are capable of binding to the enzyme. Shorter chain acyl-CoA derivatives, free CoA, and free fatty acids do not appear to bind to the enzyme. Inhibition and analog studies suggest that the methylene chain of stearyl-CoA assumes an eclipsed (\"gauche\") conformation at carbon atoms 9,10 in the enzyme-substrate complex. Furthermore, isotope rate effects obtained with deuterated stearyl-CoA derivatives indicate that hydrogen removal is the rate-limiting step of desaturation. Stearyl-CoA binds to pure liposomes and desaturase-containing liposomes, and it is this form of stearyl-CoA which appears to be the substrate for desaturase. The Arrhenius plots of desaturase activity obtained using desaturase bound to egg lecithin liposomes, in which the liquid crystalline to crystalline phase transition temperature is -5 degrees, was linear between 15 and 35 degrees, while that obtained using desaturase bound to dimyristyl lecithin liposomes showed a break at 24 degrees coinciding with the liquid crystalline to crystalline phase transition temperature for this lipid. The decrease observed in the deuterium isotope rate effect below the transition temperature indicates that a step in the reaction sequence other than hydrogen abstraction becomes rate-limiting when the lipid is in the crystalline state. In this system translational diffusion does not emerge as the rate-limiting step. The liposomes contained sufficient reductase and cytochrome b5 so that translational diffusion was not rate-limiting.", "contents": "Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid. The three purified proteins which are required for microsomal stearyl-CoA desaturation, NADH-cytochrome b5 reductase, cytochrome b5, and desaturase, have been combined with egg lecithin or dimyristyl lecithin vesicles to reconstruct a functional electron transport system capable of utilizing NADH and O2 in the desaturation of stearyl-CoA. Such preparations appear to consist of phospholipid vesicles which contain the three proteins bound to the outer surface of the vesicles. Acyl-CoA derivatives containing 12 to 19 carbon fatty acyl chains are required for desaturase activity while derivatives containing 9 to 20 carbons are capable of binding to the enzyme. Shorter chain acyl-CoA derivatives, free CoA, and free fatty acids do not appear to bind to the enzyme. Inhibition and analog studies suggest that the methylene chain of stearyl-CoA assumes an eclipsed (\"gauche\") conformation at carbon atoms 9,10 in the enzyme-substrate complex. Furthermore, isotope rate effects obtained with deuterated stearyl-CoA derivatives indicate that hydrogen removal is the rate-limiting step of desaturation. Stearyl-CoA binds to pure liposomes and desaturase-containing liposomes, and it is this form of stearyl-CoA which appears to be the substrate for desaturase. The Arrhenius plots of desaturase activity obtained using desaturase bound to egg lecithin liposomes, in which the liquid crystalline to crystalline phase transition temperature is -5 degrees, was linear between 15 and 35 degrees, while that obtained using desaturase bound to dimyristyl lecithin liposomes showed a break at 24 degrees coinciding with the liquid crystalline to crystalline phase transition temperature for this lipid. The decrease observed in the deuterium isotope rate effect below the transition temperature indicates that a step in the reaction sequence other than hydrogen abstraction becomes rate-limiting when the lipid is in the crystalline state. In this system translational diffusion does not emerge as the rate-limiting step. The liposomes contained sufficient reductase and cytochrome b5 so that translational diffusion was not rate-limiting."}
{"id": "PMID:8454", "title": "Effect of ethanesulfonic acid buffers and pH on the accumulation of a nervous system-specific protein (S-100) and a glial-enriched enzyme in a clonal line of rat astrocytes (C6).", "content": "Stationary phase cultures of a clonal line of rat astrocytes (C6) were maintained at pH values ranging from 6.0 to 8.4 using media buffered with various combinations of organic buffers or graded concentrations of bicarbonate ion at a constant CO2 tension. The accumulation of a soluble acidic protein unique to the nervous system (S-100) in media buffered with organic buffers was optimal in the pH range 6.4 to 6.8, significantly more acid than that optimal for cell growth (pH 7.0 to 7.8). Cells maintained in CO2-bicarbonate-buffered media exhibited a higher and less marked pH optimum for S-100 protein accumulation and a lower efficiency of accumulation of the protein. These data suggest that the organic buffer ions themselves, apart from their function as buffers, are influencing the accumulation of S-100. The specific activity (assayed at the enzymatic pH optimum) of a membrane-bound enzyme enriched in glial cells and myelin, 2',3'-cyclic nucleotide 3'-phosphohydrolase, was markedly pH-dependent. The optimal pH range was 6.4 to 6.7 in organic buffer controlled media. In CO2-bicarbonate controlled media the optimal pH range was only slightly higher (pH 6.6 to 7.0), but the specific activities were reduced relative to organic buffer-grown cells. The structural relationship of some of the aminoethanesulfonic acid buffers used in these experiments to certain compounds of neurochemical interest (such as taurine and alpha-flupenthixol) is noted.", "contents": "Effect of ethanesulfonic acid buffers and pH on the accumulation of a nervous system-specific protein (S-100) and a glial-enriched enzyme in a clonal line of rat astrocytes (C6). Stationary phase cultures of a clonal line of rat astrocytes (C6) were maintained at pH values ranging from 6.0 to 8.4 using media buffered with various combinations of organic buffers or graded concentrations of bicarbonate ion at a constant CO2 tension. The accumulation of a soluble acidic protein unique to the nervous system (S-100) in media buffered with organic buffers was optimal in the pH range 6.4 to 6.8, significantly more acid than that optimal for cell growth (pH 7.0 to 7.8). Cells maintained in CO2-bicarbonate-buffered media exhibited a higher and less marked pH optimum for S-100 protein accumulation and a lower efficiency of accumulation of the protein. These data suggest that the organic buffer ions themselves, apart from their function as buffers, are influencing the accumulation of S-100. The specific activity (assayed at the enzymatic pH optimum) of a membrane-bound enzyme enriched in glial cells and myelin, 2',3'-cyclic nucleotide 3'-phosphohydrolase, was markedly pH-dependent. The optimal pH range was 6.4 to 6.7 in organic buffer controlled media. In CO2-bicarbonate controlled media the optimal pH range was only slightly higher (pH 6.6 to 7.0), but the specific activities were reduced relative to organic buffer-grown cells. The structural relationship of some of the aminoethanesulfonic acid buffers used in these experiments to certain compounds of neurochemical interest (such as taurine and alpha-flupenthixol) is noted."}
{"id": "PMID:8455", "title": "Titration behavior of individual tyrosine residues of myoglobins from sperm whale, horse, and red kangaroo.", "content": "The titration behavior of individual tyrosine residues of myoglobins has been studied by observing the pH dependence of the chemical shifts of Czeta and Cgamma of these residues in natural abundance of 13C Fourier transform NMR spectra (at 15.18 MHz, in 20-mm sample tubes, at 37 degrees) of cyanoferrimyoglobins from sperm whale, horse, and red kangaroo. A comparison of the pH dependence of the spectra of the three proteins yielded specific assignments for the resonance of Tyr-151 (sperm whale) and Tyr-103 (sperm whale and horse). Selective proton decoupling yielded specific assignments for Czeta of Tyr-146 of the cyanoferrimyoglobins from horse and kangaroo, but not the corresponding assignment for sperm whale. The pH dependence of the chemical shifts indicated that only Tyr-151 and Tyr-103 are titratable tyrosine residues. Even at pH 12, Tyr-146 did not begin to titrate. The titration behavior of C zeta and Cgamma of Tyr-151 of sperm whale cyanoferrimyoglobin yielded a single pK value of 10.6. The pH dependence of the chemical shift of each of the resonances of Tyr-103 of the cyanoferrimyoglobins from horse and sperm whale could not be fitted with the use of a single pK value, but was consistent with two pK values (about 9.8 and 11.6). Furthermore, the resonances of Czeta and Cgamma of Tyr-103 broadened at high pH. The titration behavior of the tyrosines of sperm whale carbon monoxide myoglobin and horse ferrimyoglobin was also examined. A comparison of all the experimental results indicated that Tyr-151 is exposed to solvent, Tyr-146 is not exposed, and Tyr-103 exhibits intermediate behavior. These results for myoglobins in solution are consistent with expectations based on the crystal structure.", "contents": "Titration behavior of individual tyrosine residues of myoglobins from sperm whale, horse, and red kangaroo. The titration behavior of individual tyrosine residues of myoglobins has been studied by observing the pH dependence of the chemical shifts of Czeta and Cgamma of these residues in natural abundance of 13C Fourier transform NMR spectra (at 15.18 MHz, in 20-mm sample tubes, at 37 degrees) of cyanoferrimyoglobins from sperm whale, horse, and red kangaroo. A comparison of the pH dependence of the spectra of the three proteins yielded specific assignments for the resonance of Tyr-151 (sperm whale) and Tyr-103 (sperm whale and horse). Selective proton decoupling yielded specific assignments for Czeta of Tyr-146 of the cyanoferrimyoglobins from horse and kangaroo, but not the corresponding assignment for sperm whale. The pH dependence of the chemical shifts indicated that only Tyr-151 and Tyr-103 are titratable tyrosine residues. Even at pH 12, Tyr-146 did not begin to titrate. The titration behavior of C zeta and Cgamma of Tyr-151 of sperm whale cyanoferrimyoglobin yielded a single pK value of 10.6. The pH dependence of the chemical shift of each of the resonances of Tyr-103 of the cyanoferrimyoglobins from horse and sperm whale could not be fitted with the use of a single pK value, but was consistent with two pK values (about 9.8 and 11.6). Furthermore, the resonances of Czeta and Cgamma of Tyr-103 broadened at high pH. The titration behavior of the tyrosines of sperm whale carbon monoxide myoglobin and horse ferrimyoglobin was also examined. A comparison of all the experimental results indicated that Tyr-151 is exposed to solvent, Tyr-146 is not exposed, and Tyr-103 exhibits intermediate behavior. These results for myoglobins in solution are consistent with expectations based on the crystal structure."}
{"id": "PMID:8456", "title": "Studies on the alpha-adrenergic activation of hepatic glucose output. I. Studies on the alpha-adrenergic activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase in isolated rat liver parenchymal cells.", "content": "Epinephrine and the alpha-adrenergic agonist phenylephrine activated phosphorylase, glycogenolysis, and gluconeogenesis from lactate in a dose-dependent manner in isolated rat liver parenchymal cells. The half-maximally active dose of epinephrine was 10-7 M and of phenylephrine was 10(-6) M. These effects were blocked by alpha-adrenergic antagonists including phenoxybenzamine, but were largely unaffected by beta-adrenergic antagonists including propranolol. Epinephrine caused a transient 2-fold elevation of adenosine 3':5'-monophosphate (cAMP) which was abolished by propranolol and other beta blockers, but was unaffected by phenoxybenzamine and other alpha blockers. Phenoxybenzamine and propranolol were shown to be specific for their respective adrenergic receptors and to not affect the actions of glucagon or exogenous cAMP. Neither epinephrine (10-7 M), phenylephrine (10-5 M), nor glucagon (10-7 M) inactivated glycogen synthase in liver cells from fed rats. When the glycogen synthase activity ratio (-glucose 6-phosphate/+ glucose 6-phosphate) was increased from 0.09 to 0.66 by preincubation of such cells with 40 mM glucose, these agents substantially inactivated the enzyme. Incubation of hepatocytes from fed rats resulted in glycogen depletion which was correlated with an increase in the glycogen synthase activity ratio and a decrease in phosphorylase alpha activity. In hepatocytes from fasted animals, the glycogen synthase activity ratio was 0.32 +/- 0.03, and epinephrine, glucagon, and phenylephrine were able to lower this significantly. The effects of epinephrine and phenylephrine on the enzyme were blocked by phenoxybenzamine, but were largely unaffected by propranolol. Maximal phosphorylase activation in hepatocytes from fasted rats incubated with 10(-5) M phenylephrine preceded the maximal inactivation of glycogen synthase. Addition of glucose rapidly reduced, in a dose-dependent manner, both basal and phenylephrine-elevated phosphorylase alpha activity in hepatocytes prepared from fasted rats. Glucose also increased the glycogen synthase activity ratio, but this effect lagged behind the change in phosphorylase. Phenylephrine (10-5 M) and glucagon (5 x 10(-10) M) decreased by one-half the fall in phosphoryalse alpha activity seen with 10 mM glucose and markedly suppressed the elevation of glycogen synthase activity. The following conclusions are drawn from these findings. (a) The effects of epinephrine and phenylephrine on carbohydrate metabolism in rat liver parenchymal cells are mediated predominantly by alpha-adrenergic receptors. (b) Stimulation of these receptors by epinephrine or phenylephrine results in activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase by mechanisms not involving an increase in cellular cAMP. (c) Activation of beta-adrenergic receptors by epinephrine leads to the accumulation of cAMP, but this is associated with minimal activation of phosphorylase or inactivation of glycogen synthase...", "contents": "Studies on the alpha-adrenergic activation of hepatic glucose output. I. Studies on the alpha-adrenergic activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase in isolated rat liver parenchymal cells. Epinephrine and the alpha-adrenergic agonist phenylephrine activated phosphorylase, glycogenolysis, and gluconeogenesis from lactate in a dose-dependent manner in isolated rat liver parenchymal cells. The half-maximally active dose of epinephrine was 10-7 M and of phenylephrine was 10(-6) M. These effects were blocked by alpha-adrenergic antagonists including phenoxybenzamine, but were largely unaffected by beta-adrenergic antagonists including propranolol. Epinephrine caused a transient 2-fold elevation of adenosine 3':5'-monophosphate (cAMP) which was abolished by propranolol and other beta blockers, but was unaffected by phenoxybenzamine and other alpha blockers. Phenoxybenzamine and propranolol were shown to be specific for their respective adrenergic receptors and to not affect the actions of glucagon or exogenous cAMP. Neither epinephrine (10-7 M), phenylephrine (10-5 M), nor glucagon (10-7 M) inactivated glycogen synthase in liver cells from fed rats. When the glycogen synthase activity ratio (-glucose 6-phosphate/+ glucose 6-phosphate) was increased from 0.09 to 0.66 by preincubation of such cells with 40 mM glucose, these agents substantially inactivated the enzyme. Incubation of hepatocytes from fed rats resulted in glycogen depletion which was correlated with an increase in the glycogen synthase activity ratio and a decrease in phosphorylase alpha activity. In hepatocytes from fasted animals, the glycogen synthase activity ratio was 0.32 +/- 0.03, and epinephrine, glucagon, and phenylephrine were able to lower this significantly. The effects of epinephrine and phenylephrine on the enzyme were blocked by phenoxybenzamine, but were largely unaffected by propranolol. Maximal phosphorylase activation in hepatocytes from fasted rats incubated with 10(-5) M phenylephrine preceded the maximal inactivation of glycogen synthase. Addition of glucose rapidly reduced, in a dose-dependent manner, both basal and phenylephrine-elevated phosphorylase alpha activity in hepatocytes prepared from fasted rats. Glucose also increased the glycogen synthase activity ratio, but this effect lagged behind the change in phosphorylase. Phenylephrine (10-5 M) and glucagon (5 x 10(-10) M) decreased by one-half the fall in phosphoryalse alpha activity seen with 10 mM glucose and markedly suppressed the elevation of glycogen synthase activity. The following conclusions are drawn from these findings. (a) The effects of epinephrine and phenylephrine on carbohydrate metabolism in rat liver parenchymal cells are mediated predominantly by alpha-adrenergic receptors. (b) Stimulation of these receptors by epinephrine or phenylephrine results in activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase by mechanisms not involving an increase in cellular cAMP. (c) Activation of beta-adrenergic receptors by epinephrine leads to the accumulation of cAMP, but this is associated with minimal activation of phosphorylase or inactivation of glycogen synthase..."}
{"id": "PMID:8457", "title": "Studies on the alpha-andrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes.", "content": "The effects of the alpha-adrenergic agonist phenylephrine on the levels of adenosine 3':5'-monophosphate (cAMP) and the activity of the cAMP-dependent protein kinase in isolated rat liver parenchymal cells were studied. Cyclic AMP was very slightly (5 to 13%) increased in cells incubated with phenylephrine at a concentration (10(-5) M) which was maximally effective on glycogenolysis and gluconeogenesis. However, the increase was significant only at 5 min. Cyclic AMP levels with 10(-5) M phenylephrine measured at this time were reduced by the beta-adrenergic antagonist propranolol, but were unaffected by the alpha-blocker phenoxybenzamine, indicating that the elevation was due to weak beta activity of the agonist. When doses of glucagon, epinephrine, and phenylephrine which produced the same stimulation of glycogenolysis or gluconeogenesis were added to the same batches of cells, there were marked rises in cAMP with glucagon, minimal increases with epinephrine, and little or no changes with phenylephrine, indicating that the two catecholamine stimulated these processes largely by mechanisms not involving cAMP accumulation. DEAE-cellulose chromatography of homogenates of liver cells revealed two major peaks of cAMP-dependent protein kinase activity. These eluted at similar salt concentrations as the type I and II isozymes from rat heart. Optimal conditions for preservation of hormone effects on the activity of the enzyme in the cells were determined. High concentrations of phenylephrine (10(-5) M and 10(-4) M) produced a small increase (10 tp 16%) in the activity ratio (-cAMP/+cAMP) of the enzyme. This was abolished by propranolol, but not by phenoxybenzamine, indicating that it was due to weak beta activity of the agonist. The increase in the activity ratio of the kinase with 10(-5) M phenylephrine was much smaller than that produced by a glycogenolytically equivalent dose of glucagon. The changes in protein kinase induced by phenylephrine and the blockers and by glucagon were thus consistent with those in cAMP. Theophylline and 1-methyl-3-isobutylxanthine, which inhibit cAMP phosphodiesterase, potentiated the effects of phenylephrine on glycogenolysis and gluconeogenesis. The potentiations were blocked by phenoxybenzamine, but not by propranolol. Methylisobutylxanthine increased the levels of cAMP and enhanced the activation of protein kinase in cells incubated with phenylephrine. These effects were diminished or abolished by propanolol, but were unaffected by phenoxybenzamine. It is concluded from these data that alpha-adrenergic activation of glycogenolysis and gluconeogenesis in isolated rat liver parenchymal cells occurs by mechanisms not involving an increase in total cellular cAMP or activation of the cAMP-dependent protein kinase. The results also show that phosphodiesterase inhibitors potentiate alpha-adrenergic actions in hepatocytes mainly by a mechanism(s) not involving a rise in cAMP.", "contents": "Studies on the alpha-andrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes. The effects of the alpha-adrenergic agonist phenylephrine on the levels of adenosine 3':5'-monophosphate (cAMP) and the activity of the cAMP-dependent protein kinase in isolated rat liver parenchymal cells were studied. Cyclic AMP was very slightly (5 to 13%) increased in cells incubated with phenylephrine at a concentration (10(-5) M) which was maximally effective on glycogenolysis and gluconeogenesis. However, the increase was significant only at 5 min. Cyclic AMP levels with 10(-5) M phenylephrine measured at this time were reduced by the beta-adrenergic antagonist propranolol, but were unaffected by the alpha-blocker phenoxybenzamine, indicating that the elevation was due to weak beta activity of the agonist. When doses of glucagon, epinephrine, and phenylephrine which produced the same stimulation of glycogenolysis or gluconeogenesis were added to the same batches of cells, there were marked rises in cAMP with glucagon, minimal increases with epinephrine, and little or no changes with phenylephrine, indicating that the two catecholamine stimulated these processes largely by mechanisms not involving cAMP accumulation. DEAE-cellulose chromatography of homogenates of liver cells revealed two major peaks of cAMP-dependent protein kinase activity. These eluted at similar salt concentrations as the type I and II isozymes from rat heart. Optimal conditions for preservation of hormone effects on the activity of the enzyme in the cells were determined. High concentrations of phenylephrine (10(-5) M and 10(-4) M) produced a small increase (10 tp 16%) in the activity ratio (-cAMP/+cAMP) of the enzyme. This was abolished by propranolol, but not by phenoxybenzamine, indicating that it was due to weak beta activity of the agonist. The increase in the activity ratio of the kinase with 10(-5) M phenylephrine was much smaller than that produced by a glycogenolytically equivalent dose of glucagon. The changes in protein kinase induced by phenylephrine and the blockers and by glucagon were thus consistent with those in cAMP. Theophylline and 1-methyl-3-isobutylxanthine, which inhibit cAMP phosphodiesterase, potentiated the effects of phenylephrine on glycogenolysis and gluconeogenesis. The potentiations were blocked by phenoxybenzamine, but not by propranolol. Methylisobutylxanthine increased the levels of cAMP and enhanced the activation of protein kinase in cells incubated with phenylephrine. These effects were diminished or abolished by propanolol, but were unaffected by phenoxybenzamine. It is concluded from these data that alpha-adrenergic activation of glycogenolysis and gluconeogenesis in isolated rat liver parenchymal cells occurs by mechanisms not involving an increase in total cellular cAMP or activation of the cAMP-dependent protein kinase. The results also show that phosphodiesterase inhibitors potentiate alpha-adrenergic actions in hepatocytes mainly by a mechanism(s) not involving a rise in cAMP."}
{"id": "PMID:8458", "title": "Reactivity of the phosphopyridoxal groups of cystathionase.", "content": "Aminooxyacetate and alpha-amino-gamma-aminooxybutyrate (canaline) react specifically with the P-pyridoxal groups of cystathionase to produce characteristic changes in the absorption and fluorescence properties of the bound cofactor. The increase in fluorescence at 450 nm was used to monitor the reaction. Aminooxyacetate attacks the Schiff base linkage of the enzyme several times faster (k1 = 3700 M-1 min-1 and k2 = 1000 M-1 min-1) than it attacks the aldehydic carbon of free P-pyridoxal (k = 290 M-1 min-1). Similar results were obtained with canaline. The kinetic studies indicate that a Schiff base linkage in the enzyme cystathionase should offer direct kinetic advantage during the reaction between the substrate and the cofactor. It is also shown that the inhibitor L-alpha-gamma-aminobutyrate reacts with bound P-pyridoxal to form free P-pyridoxamine. The rate of formation of P-pyridoxamine parallels the rate of enzyme inactivation.", "contents": "Reactivity of the phosphopyridoxal groups of cystathionase. Aminooxyacetate and alpha-amino-gamma-aminooxybutyrate (canaline) react specifically with the P-pyridoxal groups of cystathionase to produce characteristic changes in the absorption and fluorescence properties of the bound cofactor. The increase in fluorescence at 450 nm was used to monitor the reaction. Aminooxyacetate attacks the Schiff base linkage of the enzyme several times faster (k1 = 3700 M-1 min-1 and k2 = 1000 M-1 min-1) than it attacks the aldehydic carbon of free P-pyridoxal (k = 290 M-1 min-1). Similar results were obtained with canaline. The kinetic studies indicate that a Schiff base linkage in the enzyme cystathionase should offer direct kinetic advantage during the reaction between the substrate and the cofactor. It is also shown that the inhibitor L-alpha-gamma-aminobutyrate reacts with bound P-pyridoxal to form free P-pyridoxamine. The rate of formation of P-pyridoxamine parallels the rate of enzyme inactivation."}
{"id": "PMID:8459", "title": "Digestion of native collagen, denatured collagen, and collagen fragments by extracts of rat liver lysosomes.", "content": "Extracts of highly purified lysosomes from rat liver were examined for their ability to degrade native collagen and thermally denatured collagen at pH values between 3.5 and 7.0. After a 24-h digestion at 36 degrees with the lysosomal extract at a pH of 5.5 or lower (collagen/lysosomal protein; 2/1 or 8/1), both native and denatured collagen were degraded to an extent equivalent to 60 to 70% of that observed upon total acid hydrolysis in 6 N HCl as measured by the ninhydrin reaction (570 nm). At a pH of 6.0, native collagen and denatured collagen were degraded by the mixture of lysosomal proteinases to 11% and 40% of total acid hydrolysis, respectively. At pH 6.5 AND 7.0, the corresponding values were 3% versus 33% and 0.3% versus 11%, respectively. Fragments of collagen (TCA and TCB) are produced when mammalian collagenase degrades native collagen at 25 degrees. These fragments were degraded by the lysosomal extract at 36 degrees to an extent equivalent to 28% and 8% of total acid hydrolysis at pH 6.5 and 7.0, respectively. The experiments at pH 6.5 and 7.0 were done using a collagen/lysosomal protein ratio of 2/1. At pH 5.0 (a pH which is found within secondary lysosomes), the lysosomal extracts degraded collagen to a mixture of free amino acids and small peptides. Amino acid analysis established that approximately 30% of the amino acid residues of the collagen appeared in the lysosomal hydrolysate as free amino acids. Hydroxyproline and perhaps hydroxylysine were the only amino acids found in collagen which did not appear at least to some extent as the free amino acid in this hydrolysate.", "contents": "Digestion of native collagen, denatured collagen, and collagen fragments by extracts of rat liver lysosomes. Extracts of highly purified lysosomes from rat liver were examined for their ability to degrade native collagen and thermally denatured collagen at pH values between 3.5 and 7.0. After a 24-h digestion at 36 degrees with the lysosomal extract at a pH of 5.5 or lower (collagen/lysosomal protein; 2/1 or 8/1), both native and denatured collagen were degraded to an extent equivalent to 60 to 70% of that observed upon total acid hydrolysis in 6 N HCl as measured by the ninhydrin reaction (570 nm). At a pH of 6.0, native collagen and denatured collagen were degraded by the mixture of lysosomal proteinases to 11% and 40% of total acid hydrolysis, respectively. At pH 6.5 AND 7.0, the corresponding values were 3% versus 33% and 0.3% versus 11%, respectively. Fragments of collagen (TCA and TCB) are produced when mammalian collagenase degrades native collagen at 25 degrees. These fragments were degraded by the lysosomal extract at 36 degrees to an extent equivalent to 28% and 8% of total acid hydrolysis at pH 6.5 and 7.0, respectively. The experiments at pH 6.5 and 7.0 were done using a collagen/lysosomal protein ratio of 2/1. At pH 5.0 (a pH which is found within secondary lysosomes), the lysosomal extracts degraded collagen to a mixture of free amino acids and small peptides. Amino acid analysis established that approximately 30% of the amino acid residues of the collagen appeared in the lysosomal hydrolysate as free amino acids. Hydroxyproline and perhaps hydroxylysine were the only amino acids found in collagen which did not appear at least to some extent as the free amino acid in this hydrolysate."}
{"id": "PMID:8460", "title": "Oxidative phosphorylation in right-side-out membrane vesicles from Escherichia coli.", "content": "Oxidative phosphorylation in Escherichia coli membrane vesicles with a right-side-out orientation and loaded with ADP was investigated. Substrates of the electron transport chain could energize the phosphorylation of ADP, with the order of effectiveness being D-lactate greater than reduced phenazinemethosulfate greater than succinate greater than reduced nicotinamide adenine dinucleotide. Inhibitors of D-lactate oxidation, proton conductors, and inhibitor of the Mg2+ATPase (EC 3.6.1.3) all inhibited oxidative phosphorylation when coupled to D-lactate oxidation. ATP synthesis was absent in membrane vesicles prepared from a mutant strain lacking the Mg2+ATPase. Valinomycin or nigericin partially inhibited oxidative phosphorylation in the presence of potassium. Valinomycin plus nigericin completely inhibited ATP synthesis. The effect of various agents on the respiration-dependent establishment of a transmembrane pH gradient was also examined. NaCN and carbonyl cyanide p-trifluoromethoxyphenylhydrazone inhibited the establishment of a pH gradient while dicyclohexylcarbodiimide had no effect. These results are in good agreement with a chemiosmotic model for oxidative phosphorylation.", "contents": "Oxidative phosphorylation in right-side-out membrane vesicles from Escherichia coli. Oxidative phosphorylation in Escherichia coli membrane vesicles with a right-side-out orientation and loaded with ADP was investigated. Substrates of the electron transport chain could energize the phosphorylation of ADP, with the order of effectiveness being D-lactate greater than reduced phenazinemethosulfate greater than succinate greater than reduced nicotinamide adenine dinucleotide. Inhibitors of D-lactate oxidation, proton conductors, and inhibitor of the Mg2+ATPase (EC 3.6.1.3) all inhibited oxidative phosphorylation when coupled to D-lactate oxidation. ATP synthesis was absent in membrane vesicles prepared from a mutant strain lacking the Mg2+ATPase. Valinomycin or nigericin partially inhibited oxidative phosphorylation in the presence of potassium. Valinomycin plus nigericin completely inhibited ATP synthesis. The effect of various agents on the respiration-dependent establishment of a transmembrane pH gradient was also examined. NaCN and carbonyl cyanide p-trifluoromethoxyphenylhydrazone inhibited the establishment of a pH gradient while dicyclohexylcarbodiimide had no effect. These results are in good agreement with a chemiosmotic model for oxidative phosphorylation."}
{"id": "PMID:8461", "title": "Interaction of phenols with old yellow enzyme. Physical evidence for charge-transfer complexes.", "content": "Evidence is presented that the changes in absorption spectrum obtained on complex formation between Old Yellow Enzyme and phenolic compounds are due to charge-transfer interactions. The positive correlation between the energy of the long wavelength transition and the Hammett para constant with a series of para-substituted phenols indicates that the phenol is the charge-transfer donor and the oxidized flavin of the enzyme is the charge-transfer acceptor. The same conclusion is drawn from studies in which the flavin of the native enzyme, flavin mononucleotide, was replaced by a variety of artificial flavins of different oxidation-reduction potential. The effect of pH on the dissociation constant for the enzyme-ligand binding also indicates that it is the phenolate anion, rather than the conjugate acid, which is responsible for the charge-transfer interaction. The significance of these results is discussed relative to long wavelength absorbing species detected with other flavoproteins.", "contents": "Interaction of phenols with old yellow enzyme. Physical evidence for charge-transfer complexes. Evidence is presented that the changes in absorption spectrum obtained on complex formation between Old Yellow Enzyme and phenolic compounds are due to charge-transfer interactions. The positive correlation between the energy of the long wavelength transition and the Hammett para constant with a series of para-substituted phenols indicates that the phenol is the charge-transfer donor and the oxidized flavin of the enzyme is the charge-transfer acceptor. The same conclusion is drawn from studies in which the flavin of the native enzyme, flavin mononucleotide, was replaced by a variety of artificial flavins of different oxidation-reduction potential. The effect of pH on the dissociation constant for the enzyme-ligand binding also indicates that it is the phenolate anion, rather than the conjugate acid, which is responsible for the charge-transfer interaction. The significance of these results is discussed relative to long wavelength absorbing species detected with other flavoproteins."}
{"id": "PMID:8462", "title": "Characterization of calcium binding to adipocyte plasma membranes.", "content": "Calcium binding to adipocyte plasma membranes has been assessed by equilibrium dialysis and by membrane filtration techniques. Calcium binding was specific and saturable, displaying two distinct classes of binding sites. The affinity constants and maximum binding capacities in the presence of 0.1 M KCl were 4.5 X 10(4) M-1 and 1.8 nmol/mg of protein and 2.0 X 10(3) M-1 and 13.7 nmol/mg for the high and low affinity sites, respectively. Bound calcium was totally dissociated in the presence of excess calcium within 11.0 min in two distinct phases corresponding to the two classes of sites. Association and dissociation rate constants for the high affinity sites were 7.7 X 10(2) M-1S-1 and 9.2 X 10(-3S-1 respectively. Free energy changes at 24 degrees were +6.4 kcal mol-1 for the high affinity sites and +4.5 kcal mol-1 for the low affinity sites. The high affinity sites demonstrated a pH optimum of 7.0 whereas the binding to the low affinity sites progressively increased between pH 6.0 and 9.0. Low concentrations of MgCl2 (less than 300 muM) enhanced calcium binding slightly, whereas high concentrations of KCl and MgCl2 were noncompetitive inhibitors of calcium binding. Procaine and ruthenium red had no effect on calcium binding and lanthanum was a poor inhibitor of calcium binding. This represents the first report of calcium binding to adipocyte plasma membranes and the first kinetic analysis of calcium binding to biological membranes. The specificity of this calcium-binding system in adipocyte plasma membranes suggests its importance in cellular bioregulation.", "contents": "Characterization of calcium binding to adipocyte plasma membranes. Calcium binding to adipocyte plasma membranes has been assessed by equilibrium dialysis and by membrane filtration techniques. Calcium binding was specific and saturable, displaying two distinct classes of binding sites. The affinity constants and maximum binding capacities in the presence of 0.1 M KCl were 4.5 X 10(4) M-1 and 1.8 nmol/mg of protein and 2.0 X 10(3) M-1 and 13.7 nmol/mg for the high and low affinity sites, respectively. Bound calcium was totally dissociated in the presence of excess calcium within 11.0 min in two distinct phases corresponding to the two classes of sites. Association and dissociation rate constants for the high affinity sites were 7.7 X 10(2) M-1S-1 and 9.2 X 10(-3S-1 respectively. Free energy changes at 24 degrees were +6.4 kcal mol-1 for the high affinity sites and +4.5 kcal mol-1 for the low affinity sites. The high affinity sites demonstrated a pH optimum of 7.0 whereas the binding to the low affinity sites progressively increased between pH 6.0 and 9.0. Low concentrations of MgCl2 (less than 300 muM) enhanced calcium binding slightly, whereas high concentrations of KCl and MgCl2 were noncompetitive inhibitors of calcium binding. Procaine and ruthenium red had no effect on calcium binding and lanthanum was a poor inhibitor of calcium binding. This represents the first report of calcium binding to adipocyte plasma membranes and the first kinetic analysis of calcium binding to biological membranes. The specificity of this calcium-binding system in adipocyte plasma membranes suggests its importance in cellular bioregulation."}
{"id": "PMID:8463", "title": "Reduced nicotinamide adenine dinucleotide phosphate, a structural and conformational probe of chicken liver fatty acid synthetase.", "content": "Structural and conformational organization of chicken liver fatty acid synthetase has been probed using its fluorescent coenzyme, NADPH. Three NADPH binding sites per mole of the enzyme complex, of apparently identical dissociation constant (KD = 0.6 muM) can be titrated at temperatures above 12 degrees. These results are in disagreement with the earlier studies of Hsu and Wagner (Hsu, R. Y., and Wagner, B. J. (1970) Biochemistry, 9, 245-251) in which four such sites could be titrated. At 12 degrees, the composite sites split into two subsets: a pair of sites with a KD of 0.3 muM and a third site with a Kd of 1.1 muM. At lower temperatures (5 degrees or 2 degrees), the site with weak affinity disappears, leaving a pair of sites with a Kd of 0.5 muM. Similar observations were made when the enzyme was modified with phenylmethylsulfonyl fluoride, a specific and selective inhibitor of fatty acyl-CoA deacylase (s) of the pigeon liver enzyme complex (Kumar, S. (1975) J. Biol. Chem. 250, 5150-5158). Partial modification with phenylmethylsulfonyl fluoride elicits a NADPH binding response similar to the binding observed at 12 degrees, i.e. two sets of binding sites with nonidentical dissociation constants. Further modification corresponding to the complete loss of deacylase function results in a set of two apparently identical binding sites, and the third site is not available for titration. The modified enzyme retains the two reductase functions as measured by the model substrates, acetoacetyl-N-acetylcysteamine and crotonyl-CoA. Furthermore, the addition of acetyl- and malonyl-CoA (100 muM each) to the modified enzyme lowers the NADPH binding affinity by a factor of 3. Other observations show that the quantum yield, as measured by the ratio of fluorescence intensity of bound and free NADPH, changes with temperature and ionic strength. Lowering the temperature from 30 degrees to 2 degrees increases the enhancement ratio by 50%, whereas increase in ionic strength from 0.05 to 0.2 M potassium phosphate lowers it to 50% of the original level. Measurement of NADPH binding in the presence of NADP+, NADH, NAD+ and adenosine-2'-monophospho-5'-diphosphoribose demonstrates that NADP+ shows competitive behavior for NADPH sites (KD = 10.6 muM), whereas NADH and NAD+ show noncompetitive (KD (apparent) = nearly 600 muM) and rather complicated interactions implicating nonspecific conformational alteration of the enzyme complex. The behavior of adenosine 2'-monophospho-5'-diphosphoribose is intermediate between NADP+ and NADH. These data are discussed in terms of substrate-mediated conformational changes and the moles of each of the reductase enzymes per mole of the enzyme complex, the polarity of the NADPH binding region, and the probable structure of the nicotinamide moiety when bound to the enzyme.", "contents": "Reduced nicotinamide adenine dinucleotide phosphate, a structural and conformational probe of chicken liver fatty acid synthetase. Structural and conformational organization of chicken liver fatty acid synthetase has been probed using its fluorescent coenzyme, NADPH. Three NADPH binding sites per mole of the enzyme complex, of apparently identical dissociation constant (KD = 0.6 muM) can be titrated at temperatures above 12 degrees. These results are in disagreement with the earlier studies of Hsu and Wagner (Hsu, R. Y., and Wagner, B. J. (1970) Biochemistry, 9, 245-251) in which four such sites could be titrated. At 12 degrees, the composite sites split into two subsets: a pair of sites with a KD of 0.3 muM and a third site with a Kd of 1.1 muM. At lower temperatures (5 degrees or 2 degrees), the site with weak affinity disappears, leaving a pair of sites with a Kd of 0.5 muM. Similar observations were made when the enzyme was modified with phenylmethylsulfonyl fluoride, a specific and selective inhibitor of fatty acyl-CoA deacylase (s) of the pigeon liver enzyme complex (Kumar, S. (1975) J. Biol. Chem. 250, 5150-5158). Partial modification with phenylmethylsulfonyl fluoride elicits a NADPH binding response similar to the binding observed at 12 degrees, i.e. two sets of binding sites with nonidentical dissociation constants. Further modification corresponding to the complete loss of deacylase function results in a set of two apparently identical binding sites, and the third site is not available for titration. The modified enzyme retains the two reductase functions as measured by the model substrates, acetoacetyl-N-acetylcysteamine and crotonyl-CoA. Furthermore, the addition of acetyl- and malonyl-CoA (100 muM each) to the modified enzyme lowers the NADPH binding affinity by a factor of 3. Other observations show that the quantum yield, as measured by the ratio of fluorescence intensity of bound and free NADPH, changes with temperature and ionic strength. Lowering the temperature from 30 degrees to 2 degrees increases the enhancement ratio by 50%, whereas increase in ionic strength from 0.05 to 0.2 M potassium phosphate lowers it to 50% of the original level. Measurement of NADPH binding in the presence of NADP+, NADH, NAD+ and adenosine-2'-monophospho-5'-diphosphoribose demonstrates that NADP+ shows competitive behavior for NADPH sites (KD = 10.6 muM), whereas NADH and NAD+ show noncompetitive (KD (apparent) = nearly 600 muM) and rather complicated interactions implicating nonspecific conformational alteration of the enzyme complex. The behavior of adenosine 2'-monophospho-5'-diphosphoribose is intermediate between NADP+ and NADH. These data are discussed in terms of substrate-mediated conformational changes and the moles of each of the reductase enzymes per mole of the enzyme complex, the polarity of the NADPH binding region, and the probable structure of the nicotinamide moiety when bound to the enzyme."}
{"id": "PMID:8464", "title": "Identification of the covalently bound flavin of thiamin dehydrogenase.", "content": "Thiamin dehydrogenase, a flavoprotein isolated from an unidentified soil bacterium, contains 1 mol of covalently bound FAD/mol of enzyme. A flavin peptide, isolated from tryptic-chymotryptic digests of the enzyme and hydrolyzed to the FMN level, shows a pH-dependent fluorescence yield being maximal at pH 3.5 to 4.0 and decreasing over 90% at pH 7.5 with a pKa of 5.8. Acid hydrolysis of the peptide results in an aminoacylflavin which shows a pKa of fluorescence quenching of 5.2. Absorption and electron paramagnetic resonance spectral data show the covalent substituent to be at the 8alpha position of the flavin as is the case with all known enzymes containing covalently bound flavin. The aminoacylflavin gives a negative Pauly reaction but yields 1 mol of histidine on drastic acid hydrolysis thus showing an imidazole ring nitrogen as the 8alpha substituent of the flavin. The aminoacylflavin differs from synthetic 8alpha-[N(3)-histidyl]riboflavin or its acid-modified form in pKa of fluorescence quenching, in electrophoretic mobility, in being reduced by borohydride, and in being labile to storage, yielding 8-formylriboflavin. In all of these properties, however, the 8alpha-histidylriboflavin isolated from thiamin dehydrogenase is indistinguishable from 8alpha-[N(1)-histidyl]riboflavin. It is therefore concluded that the FAD moiety of thiamin dehydrogenase is covalently linked via the 8alpha-methylene group to the N(1) position of the imidazole ring of histidine.", "contents": "Identification of the covalently bound flavin of thiamin dehydrogenase. Thiamin dehydrogenase, a flavoprotein isolated from an unidentified soil bacterium, contains 1 mol of covalently bound FAD/mol of enzyme. A flavin peptide, isolated from tryptic-chymotryptic digests of the enzyme and hydrolyzed to the FMN level, shows a pH-dependent fluorescence yield being maximal at pH 3.5 to 4.0 and decreasing over 90% at pH 7.5 with a pKa of 5.8. Acid hydrolysis of the peptide results in an aminoacylflavin which shows a pKa of fluorescence quenching of 5.2. Absorption and electron paramagnetic resonance spectral data show the covalent substituent to be at the 8alpha position of the flavin as is the case with all known enzymes containing covalently bound flavin. The aminoacylflavin gives a negative Pauly reaction but yields 1 mol of histidine on drastic acid hydrolysis thus showing an imidazole ring nitrogen as the 8alpha substituent of the flavin. The aminoacylflavin differs from synthetic 8alpha-[N(3)-histidyl]riboflavin or its acid-modified form in pKa of fluorescence quenching, in electrophoretic mobility, in being reduced by borohydride, and in being labile to storage, yielding 8-formylriboflavin. In all of these properties, however, the 8alpha-histidylriboflavin isolated from thiamin dehydrogenase is indistinguishable from 8alpha-[N(1)-histidyl]riboflavin. It is therefore concluded that the FAD moiety of thiamin dehydrogenase is covalently linked via the 8alpha-methylene group to the N(1) position of the imidazole ring of histidine."}
{"id": "PMID:8465", "title": "Association of the Ah locus with specific changes in metyrapone and ethylisocyanide binding to mouse liver microsomes.", "content": "The genetic trait of \"responsiveness,\" which refers to the capacity for induction of cytochrome P-448 and numerous monooxygenase activities by certain aromatic hydrocarbons, is known to segregate almost exclusively as a single autosomal dominant gene among progeny of appropriate crosses originating from the responsive C57BL/6 and the nonresponsive DBA/2 inbred mouse strains. In this report the allele for responsiveness is shown to be associated with (a) increases in the apparent KS values for metyrapone bound to reduced P-450; (b) increases in the ethylisocyanide difference ratio (deltaA455-490/deltaA430-490);(c) increases in the deltaA455-490 per mg of microsomal protein but not in the deltaA430-490 per mg of protein from the reduced P-450-ethylisocyanide complex; (d) an approximately 2-nm hypsochromic shift in the spectral maximum in the 446 nm region for the reduced P-450-metyrapone complex; (e) an approximately 2-nm hypsochromic shift of the absorption maximum in the 455 nm region, but not of the maximum in the 430 nm region, for the reduced P-450-ethylisocyanide complex; and (f) larger increases in the deltaA455-490 than in the deltaA430-490 per mg of microsomal protein for the reduced P450-ethylisocyanide complex as a function of increasing pH. All of these phenomena are felt to be associated with the genetically regulated induction of liver microsomal cytochrome P-448 by polycyclic aromatic compounds. Whereas increases in the total hepatic P-450 content appear to be expressed almost exclusively as a single autosomal dominant trait, the increase in apparent KS value for metyrapone bound to reduced P-450 appears to be expressed additively. The reason for this finding is unclear. The increase in apparent KS value for metyrapone in 3-methylcholanthrene-treated rats is known to occur even when the induction process is presumably blocked by treating the rat concomitantly with cycloheximide. Several lines of evidence in this report indicate that, although total P-450 content does not increase in C57BL/6N mice treated with 3-methylcholanthrene plus cycloheximide, hepatic P-448 induction does occur; P-448 induction does not occur in DBA/2N mice under these same conditions. These results indicate that cytochrome P-448 induction is relatively resistant to the inhibition of protein synthesis and that a responsive animal treated with 3-methylcholanthrene plus cycloheximide cannot be considered experimentally the same as a genetically nonresponsive animal treated with 3-methylcholanthrene alone.", "contents": "Association of the Ah locus with specific changes in metyrapone and ethylisocyanide binding to mouse liver microsomes. The genetic trait of \"responsiveness,\" which refers to the capacity for induction of cytochrome P-448 and numerous monooxygenase activities by certain aromatic hydrocarbons, is known to segregate almost exclusively as a single autosomal dominant gene among progeny of appropriate crosses originating from the responsive C57BL/6 and the nonresponsive DBA/2 inbred mouse strains. In this report the allele for responsiveness is shown to be associated with (a) increases in the apparent KS values for metyrapone bound to reduced P-450; (b) increases in the ethylisocyanide difference ratio (deltaA455-490/deltaA430-490);(c) increases in the deltaA455-490 per mg of microsomal protein but not in the deltaA430-490 per mg of protein from the reduced P-450-ethylisocyanide complex; (d) an approximately 2-nm hypsochromic shift in the spectral maximum in the 446 nm region for the reduced P-450-metyrapone complex; (e) an approximately 2-nm hypsochromic shift of the absorption maximum in the 455 nm region, but not of the maximum in the 430 nm region, for the reduced P-450-ethylisocyanide complex; and (f) larger increases in the deltaA455-490 than in the deltaA430-490 per mg of microsomal protein for the reduced P450-ethylisocyanide complex as a function of increasing pH. All of these phenomena are felt to be associated with the genetically regulated induction of liver microsomal cytochrome P-448 by polycyclic aromatic compounds. Whereas increases in the total hepatic P-450 content appear to be expressed almost exclusively as a single autosomal dominant trait, the increase in apparent KS value for metyrapone bound to reduced P-450 appears to be expressed additively. The reason for this finding is unclear. The increase in apparent KS value for metyrapone in 3-methylcholanthrene-treated rats is known to occur even when the induction process is presumably blocked by treating the rat concomitantly with cycloheximide. Several lines of evidence in this report indicate that, although total P-450 content does not increase in C57BL/6N mice treated with 3-methylcholanthrene plus cycloheximide, hepatic P-448 induction does occur; P-448 induction does not occur in DBA/2N mice under these same conditions. These results indicate that cytochrome P-448 induction is relatively resistant to the inhibition of protein synthesis and that a responsive animal treated with 3-methylcholanthrene plus cycloheximide cannot be considered experimentally the same as a genetically nonresponsive animal treated with 3-methylcholanthrene alone."}
{"id": "PMID:8466", "title": "Gallium-67 citrate scintiscanning in testicular neoplasia.", "content": "Gallium-67 citrate has been used to evaluate 19 patients with malignant tumors of the testes. Five patients with abnormal uptake of the radiotracer in the abdomen proved to have other evidence confirming metastatic spread to this site. Eight patients, with normal scan findings, surgery and lymphangiorgraphy, provided no conflicting evidence of disease although one of these patients has subsequently developed increased urinary gonadotrophin concentrations. Surgery caused an abnormal scan and such patients were excluded from the analysis pointing to the need for preoperative evaluation. The technique of 67-gallium scintigraphy appears of value in assessing the intra-abdominal spread of malignant tumors of the testes.", "contents": "Gallium-67 citrate scintiscanning in testicular neoplasia. Gallium-67 citrate has been used to evaluate 19 patients with malignant tumors of the testes. Five patients with abnormal uptake of the radiotracer in the abdomen proved to have other evidence confirming metastatic spread to this site. Eight patients, with normal scan findings, surgery and lymphangiorgraphy, provided no conflicting evidence of disease although one of these patients has subsequently developed increased urinary gonadotrophin concentrations. Surgery caused an abnormal scan and such patients were excluded from the analysis pointing to the need for preoperative evaluation. The technique of 67-gallium scintigraphy appears of value in assessing the intra-abdominal spread of malignant tumors of the testes."}
{"id": "PMID:8467", "title": "The partial replacement of the serum growth factor requirement of SV3T3 cells by lactalbumin hydrolyzate.", "content": "Lactalbumin hydrolyzate (LH), a commercially prepared, enzymatic digest of a milk protein fraction, can partially replace the serum requirement of SV3T3 cells. In a low, but obligatory, background of calf serum (0.15% v/v), LH carses a large increase in the final cell density (5-10 x over the control) while modestly steimulating the actual growth rate. Lactalbumin hydrolyzate does not contain survival activity for SV3T3 cells and does not affect the growth of 3T3 cells. Since even prolonged exposure to pH 4 or 2 results in complete abolishment of the growth-rate stimulatory capability without affecting the capacity to increase the final cell density, it is possible that the LH growth activity may consist of two dissociable components. All of LH growth activity is water soluble, autoclavable, and resists proteolytic treatment. On Sephadex G15 growth activity appears as a single peak at the void volume but on G25 it is retained beyond the void volume as a broad, skewed peak. The relevant molecular weight range lies between 1,500 and 4,000. The putative low pH resistant material is strongly adsorbed to Dowex 1 x 2 and can be displaced from the column by a reduction in the pH. A comparison of the properties of the LH factors with those of known growth promoting agents isolated from serum and various enzymatic digests indicates that these new factors do not correspond to any of these agents.", "contents": "The partial replacement of the serum growth factor requirement of SV3T3 cells by lactalbumin hydrolyzate. Lactalbumin hydrolyzate (LH), a commercially prepared, enzymatic digest of a milk protein fraction, can partially replace the serum requirement of SV3T3 cells. In a low, but obligatory, background of calf serum (0.15% v/v), LH carses a large increase in the final cell density (5-10 x over the control) while modestly steimulating the actual growth rate. Lactalbumin hydrolyzate does not contain survival activity for SV3T3 cells and does not affect the growth of 3T3 cells. Since even prolonged exposure to pH 4 or 2 results in complete abolishment of the growth-rate stimulatory capability without affecting the capacity to increase the final cell density, it is possible that the LH growth activity may consist of two dissociable components. All of LH growth activity is water soluble, autoclavable, and resists proteolytic treatment. On Sephadex G15 growth activity appears as a single peak at the void volume but on G25 it is retained beyond the void volume as a broad, skewed peak. The relevant molecular weight range lies between 1,500 and 4,000. The putative low pH resistant material is strongly adsorbed to Dowex 1 x 2 and can be displaced from the column by a reduction in the pH. A comparison of the properties of the LH factors with those of known growth promoting agents isolated from serum and various enzymatic digests indicates that these new factors do not correspond to any of these agents."}
{"id": "PMID:8468", "title": "Energy metabolism in respiration-deficient and wild type Chinese hamster fibroblasts in culture.", "content": "This paper presents a comparison of energy metabolism in wild type and respiration-deficient Chinese hamster cells. From previous work (DeFrancesco et. al., '75) it was concluded that the mutant satisfies essentially all of its energy requirements from glycolysis and in this study we measure precisely the amount of glucose consumed and lactate produced per milligram increment of protein in exponentially growing cultures. From these measurements we calculate the amount of ATP derived from glycolysis (and hence the total energy requirement for normal proliferation) to be 105 +/- 15 mumoles ATP/delta mg protein in the mutant. It is 63 +/- 10 mumoles ATP/delta mg protein derived from glycolysis in wild type cells. We present evidence that the total energy requirement of wild type cells is similar to that of the mutant suggesting that approximately 40% of the energy requirement is derived from respiration. The oxidation of glutamine appears to be more significant than the complete oxidation of glucose to CO2 in these Chinese hamster fibroblasts. The amount of ATP required by the mutant cells per milligram increment of protein is relatively independent of pH.", "contents": "Energy metabolism in respiration-deficient and wild type Chinese hamster fibroblasts in culture. This paper presents a comparison of energy metabolism in wild type and respiration-deficient Chinese hamster cells. From previous work (DeFrancesco et. al., '75) it was concluded that the mutant satisfies essentially all of its energy requirements from glycolysis and in this study we measure precisely the amount of glucose consumed and lactate produced per milligram increment of protein in exponentially growing cultures. From these measurements we calculate the amount of ATP derived from glycolysis (and hence the total energy requirement for normal proliferation) to be 105 +/- 15 mumoles ATP/delta mg protein in the mutant. It is 63 +/- 10 mumoles ATP/delta mg protein derived from glycolysis in wild type cells. We present evidence that the total energy requirement of wild type cells is similar to that of the mutant suggesting that approximately 40% of the energy requirement is derived from respiration. The oxidation of glutamine appears to be more significant than the complete oxidation of glucose to CO2 in these Chinese hamster fibroblasts. The amount of ATP required by the mutant cells per milligram increment of protein is relatively independent of pH."}
{"id": "PMID:8469", "title": "Central nervous system pH in uremia and the effects of hemodialysis.", "content": "Rapid hemodialysis of uremic animals may induce a syndrome characterized by increased cerebrospinal fluid (CSF) pressure, grand mal seizures, and electroencephalographic abnormalities. There is a fall in pH and bicarbonate concentration in CSF, and brain osmolality exceeds that of plasma, resulting in a net movement of water into the brain. This syndrome has been called experimental dialysis disequilibrium syndrome. The fall in pH of CSF may be secondary to a fall of intracellular pH (pHi) in brain. Since changes in pHi can alter intracellular osmolality in other tissues, it was decided to investigate brain pHi in uremia, and the effects of hemodialysis. Brain pHi was measured by evaluating the distribution of 14C-labeled dimethadione in brain relative to CSF, while extracellular space was calculated as the 35504=/4 space relative to CSF. In animals with acute renal failure, brain (cerebral cortex) pHi was 7.06+/-0.02 (+/-SE) while that in CSF was 7.31+/-0.02, both values not different from normal. After rapid hemodialysis (100 min) of uremic animals, plasma creatinine fell from 11.8 to 5.9 mg/dl. Brain pHi was 6.89+/-0.02 and CSF pH and 7.19+/-0.02, both values significantly lower than in uremic animals (P less than 0.01), and there was a 12% increase in brain water content. After slow hemodialysis (210 min), brain pHi (7.01+/-0.02) and pH in CSF (7.27+/-0.02) were both significantly greater than values observed after rapid hemodialysis (P less than 0.01), and brain water content was normal. None of the above maneuvers had any effect on pHi of skeletal muscle or subcortical white matter. The data show that rapid hemodialysis of uremic dogs is accompanied by a significant fall in pH of CSF and pHi in cerebral cortex. Accompanying the fall in brain pHi is cerebral edema.", "contents": "Central nervous system pH in uremia and the effects of hemodialysis. Rapid hemodialysis of uremic animals may induce a syndrome characterized by increased cerebrospinal fluid (CSF) pressure, grand mal seizures, and electroencephalographic abnormalities. There is a fall in pH and bicarbonate concentration in CSF, and brain osmolality exceeds that of plasma, resulting in a net movement of water into the brain. This syndrome has been called experimental dialysis disequilibrium syndrome. The fall in pH of CSF may be secondary to a fall of intracellular pH (pHi) in brain. Since changes in pHi can alter intracellular osmolality in other tissues, it was decided to investigate brain pHi in uremia, and the effects of hemodialysis. Brain pHi was measured by evaluating the distribution of 14C-labeled dimethadione in brain relative to CSF, while extracellular space was calculated as the 35504=/4 space relative to CSF. In animals with acute renal failure, brain (cerebral cortex) pHi was 7.06+/-0.02 (+/-SE) while that in CSF was 7.31+/-0.02, both values not different from normal. After rapid hemodialysis (100 min) of uremic animals, plasma creatinine fell from 11.8 to 5.9 mg/dl. Brain pHi was 6.89+/-0.02 and CSF pH and 7.19+/-0.02, both values significantly lower than in uremic animals (P less than 0.01), and there was a 12% increase in brain water content. After slow hemodialysis (210 min), brain pHi (7.01+/-0.02) and pH in CSF (7.27+/-0.02) were both significantly greater than values observed after rapid hemodialysis (P less than 0.01), and brain water content was normal. None of the above maneuvers had any effect on pHi of skeletal muscle or subcortical white matter. The data show that rapid hemodialysis of uremic dogs is accompanied by a significant fall in pH of CSF and pHi in cerebral cortex. Accompanying the fall in brain pHi is cerebral edema."}
{"id": "PMID:8470", "title": "Activation-induced restoration of sensorimotor functions in rats with dopamine-depleting brain lesions.", "content": "Bilateral electrolytic lesions of the lateral hypothalamus or intraventricular 6-hydroxydopamine injections produced substantial depletions of striatal dopamine in rates. All animals with brain damage showed marked sensorimotor impairments. However, they began to move and respond appropriately to environmental stimuli when placed in a sink of water, in a shallow ice bath, or among a colony of cats or rats. A reversal of the sensorimotor dysfunctions was still apparent shortly after the animals were removed from each activating situation. However, the terapeutic effects dissipated rapidly, and by 4 hr after an exposure the rats responded as poorly as they had prior to activation. These findings are strikingly similar to the \"paradoxical kinesia\" seen in parkinsonism, a clinical disorder attributed to degeneration of central dopamine-containing neurons. Collectively, they suggest the importance of activation in maintaining responsiveness to senory stimuli in rats following dopamine-depleting brain lesions.", "contents": "Activation-induced restoration of sensorimotor functions in rats with dopamine-depleting brain lesions. Bilateral electrolytic lesions of the lateral hypothalamus or intraventricular 6-hydroxydopamine injections produced substantial depletions of striatal dopamine in rates. All animals with brain damage showed marked sensorimotor impairments. However, they began to move and respond appropriately to environmental stimuli when placed in a sink of water, in a shallow ice bath, or among a colony of cats or rats. A reversal of the sensorimotor dysfunctions was still apparent shortly after the animals were removed from each activating situation. However, the terapeutic effects dissipated rapidly, and by 4 hr after an exposure the rats responded as poorly as they had prior to activation. These findings are strikingly similar to the \"paradoxical kinesia\" seen in parkinsonism, a clinical disorder attributed to degeneration of central dopamine-containing neurons. Collectively, they suggest the importance of activation in maintaining responsiveness to senory stimuli in rats following dopamine-depleting brain lesions."}
{"id": "PMID:8471", "title": "Homogenized milk: is it really the culprit in dietary-induced atherosclerosis?", "content": "Xanthine oxidase activity was assayed in commercial samples of homogenized milk subjected to pH ranging from 6.7 to 2.0 and held at room temperature for 5 min. Activity decreased sharply between pH 5.5 and 3.2. Below pH 3.2 no activity was detected. Also, rabbit anti-bovine xanthine oxidase failed to crossreact immunologically with xanthine oxidase of mouse milk. These results cast doubt on the hypothesis that dietary xanthine oxidase participates in the formation of atherosclerotic plaques.", "contents": "Homogenized milk: is it really the culprit in dietary-induced atherosclerosis? Xanthine oxidase activity was assayed in commercial samples of homogenized milk subjected to pH ranging from 6.7 to 2.0 and held at room temperature for 5 min. Activity decreased sharply between pH 5.5 and 3.2. Below pH 3.2 no activity was detected. Also, rabbit anti-bovine xanthine oxidase failed to crossreact immunologically with xanthine oxidase of mouse milk. These results cast doubt on the hypothesis that dietary xanthine oxidase participates in the formation of atherosclerotic plaques."}
{"id": "PMID:8473", "title": "Biological aspects of leukotactic factors.", "content": "Quantitation of leukotaxis involves direct visualization of migrated cells either as total cell numbers or according to depth of penetration of cells into filters. Newer approaches utilize radioactively labeled cells or movement in gel. Considerable controversy exists regarding the structural attributes of chemotactic activity, although synthetic peptides emphasize the importance of primary structure. Leukotactic factors, both complement-derived and lymphocyte-generated, have been found in many conditions both in vitro and in vivo. There is increasing evidence that the leukotactic system plays an important role in the pathogenesis of inflammation.", "contents": "Biological aspects of leukotactic factors. Quantitation of leukotaxis involves direct visualization of migrated cells either as total cell numbers or according to depth of penetration of cells into filters. Newer approaches utilize radioactively labeled cells or movement in gel. Considerable controversy exists regarding the structural attributes of chemotactic activity, although synthetic peptides emphasize the importance of primary structure. Leukotactic factors, both complement-derived and lymphocyte-generated, have been found in many conditions both in vitro and in vivo. There is increasing evidence that the leukotactic system plays an important role in the pathogenesis of inflammation."}
{"id": "PMID:8567", "title": "Monoamine-synthesizing enzymes in central dopaminergic, noradrenergic and serotonergic neurons. Immunocytochemical localization by light and electron microscopy.", "content": "The monoamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and tryptophan hydroxylase (TrH) were immunocytochemical localized in dopaminergic, noradrenergic and serotonergic neurons of rat brain by light and electron microscopy. In dopaminergic and serotonergic neurons, the respective synthesizing enzymes. TH and TrH, were distributed throughout the cytoplasm of the neuronal perikarya, dendrites, axons and terminals. The most selective accumulation of reaction product for the specific enzyme was associated: (a) in perikarya with endoplasmic reticulum, Golgi apparatus and microtubules, (b) in processes with microtubules, and (c) in terminals with dense granules or clear vesicles. The labeled terminals were characterized by their content of labeled organelles and the absence of synaptic junctions. In noradrenergic neurons, both TH and DBH were localized in the perikarya, similar to TH in dopamine neurons. TH and DBH differed in their localization within proximal axons and dendrites in that TH was associated with microtubules but DBH was not. These results provide ultrastructural evidence to suggest that monoamines may be: (a) synthesized by enzymes which are associated with different organelles depending on the portion of the neuron and the type of enzyme; (b) synthesized in both axons and dendrites and (c) released from terminals without postsynaptic membrane specializations.", "contents": "Monoamine-synthesizing enzymes in central dopaminergic, noradrenergic and serotonergic neurons. Immunocytochemical localization by light and electron microscopy. The monoamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and tryptophan hydroxylase (TrH) were immunocytochemical localized in dopaminergic, noradrenergic and serotonergic neurons of rat brain by light and electron microscopy. In dopaminergic and serotonergic neurons, the respective synthesizing enzymes. TH and TrH, were distributed throughout the cytoplasm of the neuronal perikarya, dendrites, axons and terminals. The most selective accumulation of reaction product for the specific enzyme was associated: (a) in perikarya with endoplasmic reticulum, Golgi apparatus and microtubules, (b) in processes with microtubules, and (c) in terminals with dense granules or clear vesicles. The labeled terminals were characterized by their content of labeled organelles and the absence of synaptic junctions. In noradrenergic neurons, both TH and DBH were localized in the perikarya, similar to TH in dopamine neurons. TH and DBH differed in their localization within proximal axons and dendrites in that TH was associated with microtubules but DBH was not. These results provide ultrastructural evidence to suggest that monoamines may be: (a) synthesized by enzymes which are associated with different organelles depending on the portion of the neuron and the type of enzyme; (b) synthesized in both axons and dendrites and (c) released from terminals without postsynaptic membrane specializations."}
{"id": "PMID:8568", "title": "Separation of slow reacting substance of anaphylaxis (SRS-A) from human lung into four biologically active fractions.", "content": "Slow reacting substance of anaphylaxis (SRS-A) was released from human lung passively sensitized with ragweed antibody and challenged with specific antigen E. After purification by ethanol extraction, incubation with alkali (0.1 M NaOH for 30 min at 37 degrees C) and chromatography on silicic acid and DEAE-cellulose, human SRS-A was separated into four biologically active fractions (Fractions I to IV). Arylsulfatase (Type H-1) in 0.1 M sodium acetate buffer, pH 4.5, destroyed the biologic activity of only Fraction I. All four fractions, like SO4=, inhibited the arylsulfatase activity at pH 4.5 but not at pH 6.0 when p-nitrocatechol sulfate was used as substrate. These results suggest that SRS-A contain a sulfur group and that human STS-A, like the prostaglandins, may be a family of compounds. The instability of the purified SRS-A to storage remains a major barrier to their further purification and chemical identification.", "contents": "Separation of slow reacting substance of anaphylaxis (SRS-A) from human lung into four biologically active fractions. Slow reacting substance of anaphylaxis (SRS-A) was released from human lung passively sensitized with ragweed antibody and challenged with specific antigen E. After purification by ethanol extraction, incubation with alkali (0.1 M NaOH for 30 min at 37 degrees C) and chromatography on silicic acid and DEAE-cellulose, human SRS-A was separated into four biologically active fractions (Fractions I to IV). Arylsulfatase (Type H-1) in 0.1 M sodium acetate buffer, pH 4.5, destroyed the biologic activity of only Fraction I. All four fractions, like SO4=, inhibited the arylsulfatase activity at pH 4.5 but not at pH 6.0 when p-nitrocatechol sulfate was used as substrate. These results suggest that SRS-A contain a sulfur group and that human STS-A, like the prostaglandins, may be a family of compounds. The instability of the purified SRS-A to storage remains a major barrier to their further purification and chemical identification."}
{"id": "PMID:8569", "title": "Ability of H-2 regions to induce graft-vs-host disease.", "content": "Individual young adult F1 hybrid mice were irradiated with 500 R and 24 hr later injected with 5 X 10(7) spleen cells obtained from a sex-matched parental-strain donor. The injected animals were then followed for a period of 3 months and loss of body weight, mortality rate, and other signs of fatal graft-vs-host disease (GVHD) were recorded. The donor-recipient strain combinations were selected in such a way as to provide genetic differences in the entire H-2 complex, the K or D regions alone, the K or the D end, and the central (I) regions alone. The data obtained on only few combinations indicate that strong GVHD (100% mortality rate within the first month after the injection) occurs only in those donor-recipient combinations which differ in the entire H-2 complex or in the K end (K + I regions). Much weaker GVHD (mortality rate of only 50% or less and death of individual mice spread over the entire observation period) is observed when the donor and the host differ in either the K, I, or D region alone. The degree of GVHD induced by three regions, when taken singularly, is about the same. Surprisingly, the K-region GVHD was somewhat stronger in combinations of mutant strains in comparison with recombinant-strain combinations.", "contents": "Ability of H-2 regions to induce graft-vs-host disease. Individual young adult F1 hybrid mice were irradiated with 500 R and 24 hr later injected with 5 X 10(7) spleen cells obtained from a sex-matched parental-strain donor. The injected animals were then followed for a period of 3 months and loss of body weight, mortality rate, and other signs of fatal graft-vs-host disease (GVHD) were recorded. The donor-recipient strain combinations were selected in such a way as to provide genetic differences in the entire H-2 complex, the K or D regions alone, the K or the D end, and the central (I) regions alone. The data obtained on only few combinations indicate that strong GVHD (100% mortality rate within the first month after the injection) occurs only in those donor-recipient combinations which differ in the entire H-2 complex or in the K end (K + I regions). Much weaker GVHD (mortality rate of only 50% or less and death of individual mice spread over the entire observation period) is observed when the donor and the host differ in either the K, I, or D region alone. The degree of GVHD induced by three regions, when taken singularly, is about the same. Surprisingly, the K-region GVHD was somewhat stronger in combinations of mutant strains in comparison with recombinant-strain combinations."}
{"id": "PMID:8570", "title": "Purification, specificity, and hypervariable region sequence of anti-pneumococcal polysaccharide antibodies elicited in a single rabbit.", "content": "Four homogeneous antibodies to type VIII pneumococcal polysaccharide (S8) were isolated from the serum of a single rabbit (3322) by affinity chromatography on an S8 immunoadsoebent by utilizing gradient elution with cellobiose and NaCl. The binding properties of these antibodies were determined by a radioimmunoassay with 125I-bovine gamma-globulin-S8. Cellobiose (a disaccharide unit of S8) was the immunodominant group of each of the four antibodies, but each antibody bound to this disaccharide with different relative affinities. The amino acid sequences (positions 0-40) of three of the four antibody light chains were each different both in framework and first hypervariable region sequences. The fourth antibody light chain has a blocked amino terminus. These findings indicate that antibodies elicited by a relatively simple antigen and examined at one time during the course of immunization in a single rabbit may exhibit common specificities for an oligosaccharide determinant, yet have different binding affinities for that determinant as well as different primary structures in the complementarity (hypervariable) regions and framework regions.", "contents": "Purification, specificity, and hypervariable region sequence of anti-pneumococcal polysaccharide antibodies elicited in a single rabbit. Four homogeneous antibodies to type VIII pneumococcal polysaccharide (S8) were isolated from the serum of a single rabbit (3322) by affinity chromatography on an S8 immunoadsoebent by utilizing gradient elution with cellobiose and NaCl. The binding properties of these antibodies were determined by a radioimmunoassay with 125I-bovine gamma-globulin-S8. Cellobiose (a disaccharide unit of S8) was the immunodominant group of each of the four antibodies, but each antibody bound to this disaccharide with different relative affinities. The amino acid sequences (positions 0-40) of three of the four antibody light chains were each different both in framework and first hypervariable region sequences. The fourth antibody light chain has a blocked amino terminus. These findings indicate that antibodies elicited by a relatively simple antigen and examined at one time during the course of immunization in a single rabbit may exhibit common specificities for an oligosaccharide determinant, yet have different binding affinities for that determinant as well as different primary structures in the complementarity (hypervariable) regions and framework regions."}
{"id": "PMID:8571", "title": "Participation of cyclophosphamide-sensitive T cells in graft-vs-host reactions.", "content": "Cyclophosphamide (CY)3 is toxic for a population of mouse T cells which is active in graft vs host (GVH) responses. This observation contrasts with previous reports which indicate that treatment of mice with CY regimens, similar to those used in this study, enhances the reactivity of T cells which mediate delayed type hypersensitivity to sheep red blood cells. The GVH-inducing capacity of T cells is not altered by removal of B cells by nylon wool columns. We suggest that CY-sensitive T cells may be \"regulatory cells,\" and that the effect they have depends on, among other things, the nature of the stimulating antigen to which the cells are responding and/or the assay used for study.", "contents": "Participation of cyclophosphamide-sensitive T cells in graft-vs-host reactions. Cyclophosphamide (CY)3 is toxic for a population of mouse T cells which is active in graft vs host (GVH) responses. This observation contrasts with previous reports which indicate that treatment of mice with CY regimens, similar to those used in this study, enhances the reactivity of T cells which mediate delayed type hypersensitivity to sheep red blood cells. The GVH-inducing capacity of T cells is not altered by removal of B cells by nylon wool columns. We suggest that CY-sensitive T cells may be \"regulatory cells,\" and that the effect they have depends on, among other things, the nature of the stimulating antigen to which the cells are responding and/or the assay used for study."}
{"id": "PMID:8573", "title": "Degradation of gastrin by gastric mucosal cells.", "content": "Specific binding of radiolabeled gastrin by gastric mucosal cells prepared from guinea pigs was detected and examined. Specific cell binding of gastrin was found to be both pH and temperature dependent. Maximum binding of radiolabeled gastrin by gastric mucosal cells was demonstrated at pH 7.4 and at 4 degrees C. Substantial degradation of 125I-gastrin occurred during incubation with gastric mucosal cells. Gastrin degradation was detected both by loss of immunological reactivity with antibodies to gastrin and by abolition of subsequent specific binding after prior incubation with gastric mucosal cells. Degradation of gastrin was  most marked with incubations conducted at pH 7.4 and at low pH (pH 2.0), suggesting the activities of at least two gastrin-degrading enzyme systems in the gastric mucosal cell preparation.", "contents": "Degradation of gastrin by gastric mucosal cells. Specific binding of radiolabeled gastrin by gastric mucosal cells prepared from guinea pigs was detected and examined. Specific cell binding of gastrin was found to be both pH and temperature dependent. Maximum binding of radiolabeled gastrin by gastric mucosal cells was demonstrated at pH 7.4 and at 4 degrees C. Substantial degradation of 125I-gastrin occurred during incubation with gastric mucosal cells. Gastrin degradation was detected both by loss of immunological reactivity with antibodies to gastrin and by abolition of subsequent specific binding after prior incubation with gastric mucosal cells. Degradation of gastrin was  most marked with incubations conducted at pH 7.4 and at low pH (pH 2.0), suggesting the activities of at least two gastrin-degrading enzyme systems in the gastric mucosal cell preparation."}
{"id": "PMID:8574", "title": "Renal acidification in sickle-cell disease.", "content": "Renal acidification was evaluated in patients with sickle-cell disease (HvSS) with both oral NH4CI and NaHC03 and the results were compared to those of subjects with sickle-cell trait (HbAS) and controls. The pH of arterial blood was normal in HbSS subjects but their PC02 and [HC03] were lower than those of controls. In response to NH4CI, six of 20 HbSS subjects had an abnormal minimal urine pH (greater than 5.3) and the entire HbSS group had a higher mean value than did either controls or HbAS subjects. Since none of the six HbSS subjects had evidence of proximal tubular abnormalities, it was concluded that they exhibited the syndrome of incomplete distal renal tubular acidosis. Only one of the six HbSS volunteers with an abnormal response to NH4CI and two of seven with a normal response increased their urinary PC02 normally after bicarbonate loading. PAH clearance was significantly higher and inulin clearance tended to be higher in HbSS subjects than in either controls or HbAS subjects. Maximal concentrating ability was decreased in both sickle-cell groups but more so in HbSS. No adverse effects occurred and no appearance or increase in per cent of sickled cells resulted from short-duration NH4CI acid-loading. No differences were found either in the clinical characterstics or in hematological, renal, and acid-base variables between the HbSS subjects with and without a normal response to acid-loading. The mechanism for the observed renal acidification abnormality remains unknown.", "contents": "Renal acidification in sickle-cell disease. Renal acidification was evaluated in patients with sickle-cell disease (HvSS) with both oral NH4CI and NaHC03 and the results were compared to those of subjects with sickle-cell trait (HbAS) and controls. The pH of arterial blood was normal in HbSS subjects but their PC02 and [HC03] were lower than those of controls. In response to NH4CI, six of 20 HbSS subjects had an abnormal minimal urine pH (greater than 5.3) and the entire HbSS group had a higher mean value than did either controls or HbAS subjects. Since none of the six HbSS subjects had evidence of proximal tubular abnormalities, it was concluded that they exhibited the syndrome of incomplete distal renal tubular acidosis. Only one of the six HbSS volunteers with an abnormal response to NH4CI and two of seven with a normal response increased their urinary PC02 normally after bicarbonate loading. PAH clearance was significantly higher and inulin clearance tended to be higher in HbSS subjects than in either controls or HbAS subjects. Maximal concentrating ability was decreased in both sickle-cell groups but more so in HbSS. No adverse effects occurred and no appearance or increase in per cent of sickled cells resulted from short-duration NH4CI acid-loading. No differences were found either in the clinical characterstics or in hematological, renal, and acid-base variables between the HbSS subjects with and without a normal response to acid-loading. The mechanism for the observed renal acidification abnormality remains unknown."}
{"id": "PMID:8575", "title": "Inflammatory reaction and airway damage in cystic fibrosis.", "content": "In cystic fibrosis there is chronic infection and inflammatory reaction in the airways, accompanied by destruction and shedding of airway epithelium. Leukocytes migrate into the airways and some disintegrate, liberating deoxyribonucleoprotein that is incorporated into the gel structure of the bronchial mucus. We compared the status of these processes in cystic fibrosis with that in chronic bronchitis and bronchiectasis, by examining the sputum raised from the lower airways. Measurements also were made on sputum induced in normal subjects. The results indicate that migration of leukocytes into the airways and shedding of damaged airway epithelium were minimal in the normal subjects; they were significant in the patients with chronic bronchitis, higher in those with bronchiectasis, and still higher in those with cystic fibrosis. The large increases found in the total content of DNA and solids in the cystic fibrosis sputum were due to increases in the insoluble fraction containing the whole leukocytes and particulate debris that remained when the sputum mucus gel was solubilized with mercaptoethanol. Despite the large increases in the total content of DNA and solids, the contents of mucus gel components and of deoxyribonucleoprotein from disintegrated leukocytes actually present in the mucus gel structure of the cystic fibrosis sputum were not significantly higher than in the sputum from the patients with chronic bronchitis or brochiectasis.", "contents": "Inflammatory reaction and airway damage in cystic fibrosis. In cystic fibrosis there is chronic infection and inflammatory reaction in the airways, accompanied by destruction and shedding of airway epithelium. Leukocytes migrate into the airways and some disintegrate, liberating deoxyribonucleoprotein that is incorporated into the gel structure of the bronchial mucus. We compared the status of these processes in cystic fibrosis with that in chronic bronchitis and bronchiectasis, by examining the sputum raised from the lower airways. Measurements also were made on sputum induced in normal subjects. The results indicate that migration of leukocytes into the airways and shedding of damaged airway epithelium were minimal in the normal subjects; they were significant in the patients with chronic bronchitis, higher in those with bronchiectasis, and still higher in those with cystic fibrosis. The large increases found in the total content of DNA and solids in the cystic fibrosis sputum were due to increases in the insoluble fraction containing the whole leukocytes and particulate debris that remained when the sputum mucus gel was solubilized with mercaptoethanol. Despite the large increases in the total content of DNA and solids, the contents of mucus gel components and of deoxyribonucleoprotein from disintegrated leukocytes actually present in the mucus gel structure of the cystic fibrosis sputum were not significantly higher than in the sputum from the patients with chronic bronchitis or brochiectasis."}
{"id": "PMID:8578", "title": "In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus.", "content": "In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.", "contents": "In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus. In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA."}
{"id": "PMID:8579", "title": "The mediator of cellular immunity. XII. Inhibition of activated T cells by Newcastle disease virus.", "content": "Newcastle disease virus (NDV) can interact in at least two ways with rat T cells. By adsorbing to circulating lymphocytes, the virus can transiently deflect the cells from lymph nodes and inflammatory exudates induced in the peritoneal cavity. T cells are affected regardless of age, state of activation, or position in the mitotic cycle. The effect is reversible and is mediated not only by infectious (I)-NDV, but also by UV-NDV which cannot achieve a complete replication cycle in eggs. But I-NDV has another lasting effect on activated T cells. It is revealed in the failure of virus-treated thoracic duct lymphocytes to transfer cellular resistance to Listeria monocytogenes, delayed-type hypersensitivity to soluble antigens of the parasite, and the permanent exclusion of labeled S-phase lymphocytes from inflammatory foci. Activated T cells are inhibited by virus multiplicites which have little if any effect upon  the proliferative potential of antigen-sensitive T cells or localization of labeled small lymphocytes in lymph nodes. The underlying mechanism has not been determined; however, there are reasons for thinking that NDV has a lethal effect upon activated T cells, because the latter are permissive for virus replication.", "contents": "The mediator of cellular immunity. XII. Inhibition of activated T cells by Newcastle disease virus. Newcastle disease virus (NDV) can interact in at least two ways with rat T cells. By adsorbing to circulating lymphocytes, the virus can transiently deflect the cells from lymph nodes and inflammatory exudates induced in the peritoneal cavity. T cells are affected regardless of age, state of activation, or position in the mitotic cycle. The effect is reversible and is mediated not only by infectious (I)-NDV, but also by UV-NDV which cannot achieve a complete replication cycle in eggs. But I-NDV has another lasting effect on activated T cells. It is revealed in the failure of virus-treated thoracic duct lymphocytes to transfer cellular resistance to Listeria monocytogenes, delayed-type hypersensitivity to soluble antigens of the parasite, and the permanent exclusion of labeled S-phase lymphocytes from inflammatory foci. Activated T cells are inhibited by virus multiplicites which have little if any effect upon  the proliferative potential of antigen-sensitive T cells or localization of labeled small lymphocytes in lymph nodes. The underlying mechanism has not been determined; however, there are reasons for thinking that NDV has a lethal effect upon activated T cells, because the latter are permissive for virus replication."}
{"id": "PMID:8580", "title": "An improved method for the determination of creatine kinase activity in serum.", "content": "An improved method for the determination of creatine kinase activity (EC 2.7.3.2) is described. For the reactivation of creatine kinase serum is first preincubated in the test solution in the presence of dithioerythritol. Then the enzymatic reaction is started by adding creatine phosphate. By optimizing the concentrations in the test solution and by altering the measurement procedure using dithioerythritol as reactivator, the assay is made more sensitive, and a far higher enzyme activity in serum is measured in comparison with other recommended tests. The reaction rate is linear for ten minutes up to 700 U/l. An increase in activity by enzyme dilution was not observed. In this study a sensitivity of detection of 0.9 U/l was achieved. This would be especially advantageous in the detection of the isoenzymes of creatine kinase after chromatography. Within-run precision was 1.2% (CV), day-to-day precision was 2.0% (CV). The test solution is stable for at least 24 hours.", "contents": "An improved method for the determination of creatine kinase activity in serum. An improved method for the determination of creatine kinase activity (EC 2.7.3.2) is described. For the reactivation of creatine kinase serum is first preincubated in the test solution in the presence of dithioerythritol. Then the enzymatic reaction is started by adding creatine phosphate. By optimizing the concentrations in the test solution and by altering the measurement procedure using dithioerythritol as reactivator, the assay is made more sensitive, and a far higher enzyme activity in serum is measured in comparison with other recommended tests. The reaction rate is linear for ten minutes up to 700 U/l. An increase in activity by enzyme dilution was not observed. In this study a sensitivity of detection of 0.9 U/l was achieved. This would be especially advantageous in the detection of the isoenzymes of creatine kinase after chromatography. Within-run precision was 1.2% (CV), day-to-day precision was 2.0% (CV). The test solution is stable for at least 24 hours."}
{"id": "PMID:8581", "title": "[The determination of cystine aminopoptidase (oxytocinase) with a ENI fast analyzer (author's transl)].", "content": "A procedure for the determination of cystine aminopeptidase activity was adapted to a fast analyzer. The various reaction parameters were checked. The precision of the method was about 5%. Cystine aminopeptidase activity was stable for long storage periods at +4 degrees C and -20 degrees C. The normal range for the terminal weeks of pregnancy was determined on samples from female patients with normal pregnancies.", "contents": "[The determination of cystine aminopoptidase (oxytocinase) with a ENI fast analyzer (author's transl)]. A procedure for the determination of cystine aminopeptidase activity was adapted to a fast analyzer. The various reaction parameters were checked. The precision of the method was about 5%. Cystine aminopeptidase activity was stable for long storage periods at +4 degrees C and -20 degrees C. The normal range for the terminal weeks of pregnancy was determined on samples from female patients with normal pregnancies."}
{"id": "PMID:8583", "title": "Spectrophotometric studies on the pH of frog skeletal muscle. PH change during and after contractile activity.", "content": "The spectral characteristics of the pH-sensitive dyes neutral red (NR) and bromcresol purple (BCP) were utilized for studies of the changing intracellular pH (pHi) of sartorius muscles from Rana pipiens, both during the course of an isometric twitch and during recovery metabolism subsequent to a train of twitches. The information from the two dissimilar dyes correlated to confirm the methodology. Neither the fast realkalinization observed during a twitch nor the slow alkalizing phase of recovery metabolism was affected in an obvious manner when phosphocreatine (PC) hydrolysis was blocked by 1-fluoro-2,4-dinitrobenzene (FDNB). Iodoacetic acid (IAA) did inhibit the slow acidic phase of recovery metabolism. The conclusion is made that alkalizing reactions other than PC breakdown must be considered as operative at these levels of activity. Hypertonic solutions altered twitch tension and time course without altering the pHi shifts observed until approximately 75% of the twitch amplitude was abolished. Multiple effects of hypertonic solutions as the muscle approach tonic equilibrium are proposed.", "contents": "Spectrophotometric studies on the pH of frog skeletal muscle. PH change during and after contractile activity. The spectral characteristics of the pH-sensitive dyes neutral red (NR) and bromcresol purple (BCP) were utilized for studies of the changing intracellular pH (pHi) of sartorius muscles from Rana pipiens, both during the course of an isometric twitch and during recovery metabolism subsequent to a train of twitches. The information from the two dissimilar dyes correlated to confirm the methodology. Neither the fast realkalinization observed during a twitch nor the slow alkalizing phase of recovery metabolism was affected in an obvious manner when phosphocreatine (PC) hydrolysis was blocked by 1-fluoro-2,4-dinitrobenzene (FDNB). Iodoacetic acid (IAA) did inhibit the slow acidic phase of recovery metabolism. The conclusion is made that alkalizing reactions other than PC breakdown must be considered as operative at these levels of activity. Hypertonic solutions altered twitch tension and time course without altering the pHi shifts observed until approximately 75% of the twitch amplitude was abolished. Multiple effects of hypertonic solutions as the muscle approach tonic equilibrium are proposed."}
{"id": "PMID:8584", "title": "Acetyl-CoA production and utilization during growth of the facultative methylotroph Pseudomonas AM1 on ethanol, malonate and 3-hydroxybutyrate.", "content": "In Pseudomonas AM1, conversion of 3-hydroxybutyrate to acetyl-CoA is mediated by an inducible 3-hydroxybutyrate dehydrogenase, an acetoacetate: succinate coenzyme A transferase (specific for succinyl-CoA) and an inducible beta-ketothiolase. Ethanol is oxidized to acetate by the same enzymes as are involved in methanol oxidation to formate. An inducible acetyl-CoA synthetase has been partially purified and characterized; it is essential for growth only on ethanol, malonate and acetate plus glyoxylate, as shown by the growth characteristics of a mutant (ICT54) lacking this enzyme. Free acetate is not involved in the assimilation of acetyl-CoA, and hydroxypyruvate reductase is not involved in the oxidation of acetyl-CoA to glyoxylate during growth on 3-hydroxybutyrate. A mutant (ICT51), lacking 'malate synthase' activity has been isolated and its characteristics indicate that this activity is normally essential for growth, of Pseudomonas AM1 on ethanol, malonate and 3-hydroxybutyrate, but not for growth on other substrates such as pyruvate, succinate and C1 compounds. The growth properties of a revertant (ICT51R) and of a mutant lacking malyl-CoA lyase (PCT57) indicate that an alternative route must exist for assimilation of compounds metabolized exclusively by way of acetyl-CoA.", "contents": "Acetyl-CoA production and utilization during growth of the facultative methylotroph Pseudomonas AM1 on ethanol, malonate and 3-hydroxybutyrate. In Pseudomonas AM1, conversion of 3-hydroxybutyrate to acetyl-CoA is mediated by an inducible 3-hydroxybutyrate dehydrogenase, an acetoacetate: succinate coenzyme A transferase (specific for succinyl-CoA) and an inducible beta-ketothiolase. Ethanol is oxidized to acetate by the same enzymes as are involved in methanol oxidation to formate. An inducible acetyl-CoA synthetase has been partially purified and characterized; it is essential for growth only on ethanol, malonate and acetate plus glyoxylate, as shown by the growth characteristics of a mutant (ICT54) lacking this enzyme. Free acetate is not involved in the assimilation of acetyl-CoA, and hydroxypyruvate reductase is not involved in the oxidation of acetyl-CoA to glyoxylate during growth on 3-hydroxybutyrate. A mutant (ICT51), lacking 'malate synthase' activity has been isolated and its characteristics indicate that this activity is normally essential for growth, of Pseudomonas AM1 on ethanol, malonate and 3-hydroxybutyrate, but not for growth on other substrates such as pyruvate, succinate and C1 compounds. The growth properties of a revertant (ICT51R) and of a mutant lacking malyl-CoA lyase (PCT57) indicate that an alternative route must exist for assimilation of compounds metabolized exclusively by way of acetyl-CoA."}
{"id": "PMID:8585", "title": "Defined and semi-defined media for the growth of amoebae of Physarum polycephalum.", "content": "Amoebae of the true slime mould Physarum polycephalum were cultured in two fully-defined liquid media containing amino acids, glucose, three vitamins and a buffered salts solution. Absolute requirements were demonstrated for methionine, haematin, thiamine and biotin, all of which were known to be specific requirements of the plasmodial stage. Methods are described for large-scale culture in three semi-defined media.", "contents": "Defined and semi-defined media for the growth of amoebae of Physarum polycephalum. Amoebae of the true slime mould Physarum polycephalum were cultured in two fully-defined liquid media containing amino acids, glucose, three vitamins and a buffered salts solution. Absolute requirements were demonstrated for methionine, haematin, thiamine and biotin, all of which were known to be specific requirements of the plasmodial stage. Methods are described for large-scale culture in three semi-defined media."}
{"id": "PMID:8586", "title": "Formation of ethylene by Escherichia coli.", "content": "Escherichia coli strain SPA O converts methionine to ethylene by an inducible enzyme system. L-Cysteine, L-homocysteine, methionine derivatives and the sulphur-containing analogues of L-methionine also act as precursors of ethylene. Ethylene is produced by cell suspensions only in the presence of air; cell-free preparations can produce ethylene aerobically and anaerobically, but the extent to which they do so depends on the mode of culture growth. Light stimulates ethylene production by cell suspensions and its presence is essential for production by cell-free preparations. The kinetics of ethylene biogenesis and its pH and temperature optima suggest that ethylene is a secondary metabolite.", "contents": "Formation of ethylene by Escherichia coli. Escherichia coli strain SPA O converts methionine to ethylene by an inducible enzyme system. L-Cysteine, L-homocysteine, methionine derivatives and the sulphur-containing analogues of L-methionine also act as precursors of ethylene. Ethylene is produced by cell suspensions only in the presence of air; cell-free preparations can produce ethylene aerobically and anaerobically, but the extent to which they do so depends on the mode of culture growth. Light stimulates ethylene production by cell suspensions and its presence is essential for production by cell-free preparations. The kinetics of ethylene biogenesis and its pH and temperature optima suggest that ethylene is a secondary metabolite."}
{"id": "PMID:8587", "title": "The regulation of glutamine transport and glutamine synthetase in Salmonella typhimurium.", "content": "Transport of glutamine by the high-affinity transport system is regulated by the nitrogen status of the medium. With high concentrations of ammonia, transport is repressed; whereas with Casamino acids, transport is elevated, showing behaviour similar to glutamine synthetase. A glutamine auxotroph, lacking glutamine synthetase activity, had elevated transport activity even in the presence of high concentrations of ammonia (and glutamine). This suggests that glutamine synthetase is involved in the regulation of the transport system. A mutant with low glutamate synthase activity had low glutamine transport and glutamine synthetase activities, which could not be derepressed. A mutant in the high-affinity glutamine transport system showed normal regulation of glutamate synthase and glutamine synthetase. Possible mechanisms for this regulation are discussed.", "contents": "The regulation of glutamine transport and glutamine synthetase in Salmonella typhimurium. Transport of glutamine by the high-affinity transport system is regulated by the nitrogen status of the medium. With high concentrations of ammonia, transport is repressed; whereas with Casamino acids, transport is elevated, showing behaviour similar to glutamine synthetase. A glutamine auxotroph, lacking glutamine synthetase activity, had elevated transport activity even in the presence of high concentrations of ammonia (and glutamine). This suggests that glutamine synthetase is involved in the regulation of the transport system. A mutant with low glutamate synthase activity had low glutamine transport and glutamine synthetase activities, which could not be derepressed. A mutant in the high-affinity glutamine transport system showed normal regulation of glutamate synthase and glutamine synthetase. Possible mechanisms for this regulation are discussed."}
{"id": "PMID:8589", "title": "Electrodermal, cardiac, and respiratory activity to repeated cold pressor stimulation in drug addicts.", "content": "Skin conductance responses (SCRs), heart rate (HR), and respiration were recorded in various rest, cold pressor (CP), and CP recovery phases in 20 former drug users (DG) and 20 control Ss (CG), matched on sex and age in a repeated measures design. With regard to the abused drugs (barbiturates and narcotic analgesics), the hypothesis was tested that autonomic responses are decreased after long-term use of barbiturates and narcotic analgesics. The results partially supported that hypothesis: (a) SCRs, HR change, and HR deceleration were significantly lower in DG compared to control Ss; (b) HR baseline, respiration rate, and amplitude, however, tended to be increased in DG in the rest and CP phases. A second hypothesis, addressed to different habituation rates of SCRs and HR in both groups, was confirmed for SCRs and partly for HR, indicating that the habituation rates of SCRs, HR change, and HR deceleration were greater in DG than in CG. A third question concerned the consistency of SCR and HR results in both sessions. A trend for consistent results was found as the direction of the group differences was the same in sessions 1 and 2. The CP results were compared with similar findings in the same Ss during visual and auditory stimulation.", "contents": "Electrodermal, cardiac, and respiratory activity to repeated cold pressor stimulation in drug addicts. Skin conductance responses (SCRs), heart rate (HR), and respiration were recorded in various rest, cold pressor (CP), and CP recovery phases in 20 former drug users (DG) and 20 control Ss (CG), matched on sex and age in a repeated measures design. With regard to the abused drugs (barbiturates and narcotic analgesics), the hypothesis was tested that autonomic responses are decreased after long-term use of barbiturates and narcotic analgesics. The results partially supported that hypothesis: (a) SCRs, HR change, and HR deceleration were significantly lower in DG compared to control Ss; (b) HR baseline, respiration rate, and amplitude, however, tended to be increased in DG in the rest and CP phases. A second hypothesis, addressed to different habituation rates of SCRs and HR in both groups, was confirmed for SCRs and partly for HR, indicating that the habituation rates of SCRs, HR change, and HR deceleration were greater in DG than in CG. A third question concerned the consistency of SCR and HR results in both sessions. A trend for consistent results was found as the direction of the group differences was the same in sessions 1 and 2. The CP results were compared with similar findings in the same Ss during visual and auditory stimulation."}
{"id": "PMID:8592", "title": "Physiological and pharmacological aids in the differential diagnosis of tremor.", "content": "Physiological and pharmacological studies of more than 150 patients with movement disorders are reported. Particular attention is paid to the differentiation of various types of tremor on the basis of rate, rhythm, and pattern of EMG activity in antagonistic muscles. The typical 'tremor-at-rest' of Parkinson's disease--3-7 Hz activity which alternates between antagonistic muscles--is suppressed, at least briefly, during voluntary activity, at which time typical 8--12 Hz 'physiological tremor' may be seen. Essential tremor and its familial or senile variants also have a characteristic EMG pattern during voluntary activity--5-8 Hz bursts of activity which are synchronous in antagonistic muscles. This type of tremor may also be present in patients with Parkinson's disease and in certain kinships with a Charcot-Marie-Tooth polyneuropathy. Other tremors in association with polyneuropathy ('neuropathic tremor') have different physiological characteristics. Myoclonus is of essentially two types ('positive' with EMG bursts and 'negative' with brief pauses in ongoing activity, as with asterixis) and may, at times, mimic tremor. Certain specific tremors respond predictably to specific pharmacological therapy.", "contents": "Physiological and pharmacological aids in the differential diagnosis of tremor. Physiological and pharmacological studies of more than 150 patients with movement disorders are reported. Particular attention is paid to the differentiation of various types of tremor on the basis of rate, rhythm, and pattern of EMG activity in antagonistic muscles. The typical 'tremor-at-rest' of Parkinson's disease--3-7 Hz activity which alternates between antagonistic muscles--is suppressed, at least briefly, during voluntary activity, at which time typical 8--12 Hz 'physiological tremor' may be seen. Essential tremor and its familial or senile variants also have a characteristic EMG pattern during voluntary activity--5-8 Hz bursts of activity which are synchronous in antagonistic muscles. This type of tremor may also be present in patients with Parkinson's disease and in certain kinships with a Charcot-Marie-Tooth polyneuropathy. Other tremors in association with polyneuropathy ('neuropathic tremor') have different physiological characteristics. Myoclonus is of essentially two types ('positive' with EMG bursts and 'negative' with brief pauses in ongoing activity, as with asterixis) and may, at times, mimic tremor. Certain specific tremors respond predictably to specific pharmacological therapy."}
{"id": "PMID:8601", "title": "The reliability of pH-values in fetal blood samples - A study of the second stage.", "content": "In 119 cases fetal blood analysis (FBA) was done in the last 15 minutes before birth together with blood sampling from the umbilical artery (UA) immediately after delivery before the first breath. Using the measured pH-values we investigated the relationship between these variables, in particular the degree of influence of considerable caput succedaneum on pH-values in peripheral blood. Our investigation was performed during the time just before delivery, when the disturbance of blood circulation in the presenting fetal part whuld have the highest influence on pH-values measured from peripheral blood samples. We kept in mind especially the critiques of FBA by WULF et al. [21] and ASSALI [2]. As other authors have concluded, we found a high degree of correlation between the pH evaluated by FBA and that determined in the umbilical artery blood. The coefficient of correlation was: pHact r=0.82 pHqu40 r=0.78. The relationship between the corresponding pHvalues in peripheral (FBA) and arterial (UA) blood is given in Fig. 1 a and Fig. 1 b. The correlation of quadrants showed for the actual pH as well for the pHqu40 p less than 0.01. As derived form this, a high degree of correlation between the pH-values can be seen. The mean pH-values were: (see article) 42 of the children had a severe or moderate caput succedaneum. Fig. 2a and 2b show the relationship between central and peripheral pH-values in these cases. Again a good correlation between the pH-values was observed as in the whole collective. The coefficient of correlation was: pHact r=0.78 pHqu40 r=0.79. Caput succedaneum seems to have only minimal influence on the pH of blood obtained from the presenting fetal part. These results lead us to conclude that blood sampling from the presenting fetal part in the second stage provides almost indentical pH-values as in the central fetal blood.", "contents": "The reliability of pH-values in fetal blood samples - A study of the second stage. In 119 cases fetal blood analysis (FBA) was done in the last 15 minutes before birth together with blood sampling from the umbilical artery (UA) immediately after delivery before the first breath. Using the measured pH-values we investigated the relationship between these variables, in particular the degree of influence of considerable caput succedaneum on pH-values in peripheral blood. Our investigation was performed during the time just before delivery, when the disturbance of blood circulation in the presenting fetal part whuld have the highest influence on pH-values measured from peripheral blood samples. We kept in mind especially the critiques of FBA by WULF et al. [21] and ASSALI [2]. As other authors have concluded, we found a high degree of correlation between the pH evaluated by FBA and that determined in the umbilical artery blood. The coefficient of correlation was: pHact r=0.82 pHqu40 r=0.78. The relationship between the corresponding pHvalues in peripheral (FBA) and arterial (UA) blood is given in Fig. 1 a and Fig. 1 b. The correlation of quadrants showed for the actual pH as well for the pHqu40 p less than 0.01. As derived form this, a high degree of correlation between the pH-values can be seen. The mean pH-values were: (see article) 42 of the children had a severe or moderate caput succedaneum. Fig. 2a and 2b show the relationship between central and peripheral pH-values in these cases. Again a good correlation between the pH-values was observed as in the whole collective. The coefficient of correlation was: pHact r=0.78 pHqu40 r=0.79. Caput succedaneum seems to have only minimal influence on the pH of blood obtained from the presenting fetal part. These results lead us to conclude that blood sampling from the presenting fetal part in the second stage provides almost indentical pH-values as in the central fetal blood."}
{"id": "PMID:8604", "title": "Interfacial properties of polymethyl alpha-cyanoacrylate and polybutyl alpha-cyanoacrylate.", "content": "Several physical properties of two polyalkyl alpha-cyanoacrylates relevant to their use in pharmaceutical dosage forms have been investigated. Formation of polymer films at several oil-water interfaces reveals films of diverse morphology. The retardation of solute transfer across an oil-water interface caused by the presence of polymer films formed in situ from the monomers has revealed that the methyl derivative forms the more effective barrier to the test solute, gentian violet. The emulsion-stabilizing properties of the methyl polymer have been studied, and the film-forming properties of the monomers spread from benzene onto water surfaces have been examined using a surface balance.", "contents": "Interfacial properties of polymethyl alpha-cyanoacrylate and polybutyl alpha-cyanoacrylate. Several physical properties of two polyalkyl alpha-cyanoacrylates relevant to their use in pharmaceutical dosage forms have been investigated. Formation of polymer films at several oil-water interfaces reveals films of diverse morphology. The retardation of solute transfer across an oil-water interface caused by the presence of polymer films formed in situ from the monomers has revealed that the methyl derivative forms the more effective barrier to the test solute, gentian violet. The emulsion-stabilizing properties of the methyl polymer have been studied, and the film-forming properties of the monomers spread from benzene onto water surfaces have been examined using a surface balance."}
{"id": "PMID:8605", "title": "Colorimetric analysis of immunogenic impurities in acetylsalicylic acid.", "content": "A rapid and convenient colorimetric method is described for the quantitative determination of the immunogenic impurities in acetylsalicylic acid, acetylsalicylsalicylic acid and acetylsalicylic anhydride. The method involves initial aminolysis of the compounds by ammonia to give salicylamide and subsequent coupling of this with 4-amino-phenazone in the presence of an oxidizing agent. In conjunction with a previously described method for analysis of the anhydride the method allows a specific determination of acetylsalicylsalicylic acid in concentrations down to 0-005%. Applying the methods to 15 different commercial acetylsalicylic acid samples and formulations, acetylsalicylic anhydride and acetylsalicylsalicylic acid were found to be present in amounts ranging from 0-001 to 0-024% and from 0-006 to 0-58% (w/w), respectively.", "contents": "Colorimetric analysis of immunogenic impurities in acetylsalicylic acid. A rapid and convenient colorimetric method is described for the quantitative determination of the immunogenic impurities in acetylsalicylic acid, acetylsalicylsalicylic acid and acetylsalicylic anhydride. The method involves initial aminolysis of the compounds by ammonia to give salicylamide and subsequent coupling of this with 4-amino-phenazone in the presence of an oxidizing agent. In conjunction with a previously described method for analysis of the anhydride the method allows a specific determination of acetylsalicylsalicylic acid in concentrations down to 0-005%. Applying the methods to 15 different commercial acetylsalicylic acid samples and formulations, acetylsalicylic anhydride and acetylsalicylsalicylic acid were found to be present in amounts ranging from 0-001 to 0-024% and from 0-006 to 0-58% (w/w), respectively."}
{"id": "PMID:8606", "title": "Methylmercury and the skeletal muscle receptor.", "content": "Methylmercury at bath concentration of 2 X 10(-5) M was capable of inhibiting muscular contractions of the isolated rat phrenic-nerve hemidiaphragm preparation. At the height of inhibition, nerve action potential could still be recorded and the muscles continued to respond to direct stimulation. The inhibition was not reversible with L-cysteine or D-penicillamine but limited protection was possible by prior treatment with (+)-tubocurarine. Treatment of frog rectus muscles with methylmercury (0-2 mM for 15 min) resulted in a shift to the right of 1 log unit in the dose response curve to acetylcholine and a reduction in the maximum response of the tissue. The observed inhibitory action of methylmercury on neuromuscular transmission may be explained by an action on the disulphide bond believed to be present on a cholinergic receptor.", "contents": "Methylmercury and the skeletal muscle receptor. Methylmercury at bath concentration of 2 X 10(-5) M was capable of inhibiting muscular contractions of the isolated rat phrenic-nerve hemidiaphragm preparation. At the height of inhibition, nerve action potential could still be recorded and the muscles continued to respond to direct stimulation. The inhibition was not reversible with L-cysteine or D-penicillamine but limited protection was possible by prior treatment with (+)-tubocurarine. Treatment of frog rectus muscles with methylmercury (0-2 mM for 15 min) resulted in a shift to the right of 1 log unit in the dose response curve to acetylcholine and a reduction in the maximum response of the tissue. The observed inhibitory action of methylmercury on neuromuscular transmission may be explained by an action on the disulphide bond believed to be present on a cholinergic receptor."}
{"id": "PMID:8607", "title": "A method for screening diuretic agents in the mouse: an investigation of sexual differences.", "content": "Acetazolamide, aminophyline, frusemide, ethacrynic acid and triamterene were tested for diuretic action at dosages of 3, 10 and 30 mg kg-1 (s.c.) in male and female mice. Each drug significantly raised sodium excretion and all but acetazolamide elevated urine volume and chloride excretion. Potassium excretion was significantly raised by acetazolamide and frusemide. Acetazolamide and triamterene evoked urinary alkalinization whereas frusemide and ethacrynic acid reduced urinary pH. Female mice were markedly more sensitive than males to the diuretic, natriuretic, chloruretic and urinary acidfying actions of ethacrynic acid.", "contents": "A method for screening diuretic agents in the mouse: an investigation of sexual differences. Acetazolamide, aminophyline, frusemide, ethacrynic acid and triamterene were tested for diuretic action at dosages of 3, 10 and 30 mg kg-1 (s.c.) in male and female mice. Each drug significantly raised sodium excretion and all but acetazolamide elevated urine volume and chloride excretion. Potassium excretion was significantly raised by acetazolamide and frusemide. Acetazolamide and triamterene evoked urinary alkalinization whereas frusemide and ethacrynic acid reduced urinary pH. Female mice were markedly more sensitive than males to the diuretic, natriuretic, chloruretic and urinary acidfying actions of ethacrynic acid."}
{"id": "PMID:8608", "title": "Anti-inflammatory actions of dapsone and its related biochemistry.", "content": "Dapsone has been examined by two established animal anti-inflammatory models and found to possess anti-inflammatory activity comparable with established non-steroidal anti-inflammatory drugs. Dapsone also possess some biochemical properties common to other anti-inflammatory drugs.", "contents": "Anti-inflammatory actions of dapsone and its related biochemistry. Dapsone has been examined by two established animal anti-inflammatory models and found to possess anti-inflammatory activity comparable with established non-steroidal anti-inflammatory drugs. Dapsone also possess some biochemical properties common to other anti-inflammatory drugs."}
{"id": "PMID:8609", "title": "Brain tyrosine hydroxylase activity and systolic blood pressure in rats treated with either deoxycorticosterone and salt or angiotensin.", "content": "The hypertension induced in adult male rats by doca/salt was found to be accompanied by a significant rise in whole brain tyrosine hydroxylase (TH) activity. A smaller hypertensive effect, produced by angiotensin (750 ng kg-1 daily) was also accompanied by a proportional rise in whole brain TH activity. The specific antagonists spironolactone and saralasin completely blocked both responses in the doca/salt- and angiotensin-treated animals respectively and spironolactone showed a partial inhibition of the effects of angiotensin. In all the animals treated there was a clear correlation between systolic blood pressure and whole brain TH activity. The significance of these changes is discussed in the light of the central mechanism of hypertension.", "contents": "Brain tyrosine hydroxylase activity and systolic blood pressure in rats treated with either deoxycorticosterone and salt or angiotensin. The hypertension induced in adult male rats by doca/salt was found to be accompanied by a significant rise in whole brain tyrosine hydroxylase (TH) activity. A smaller hypertensive effect, produced by angiotensin (750 ng kg-1 daily) was also accompanied by a proportional rise in whole brain TH activity. The specific antagonists spironolactone and saralasin completely blocked both responses in the doca/salt- and angiotensin-treated animals respectively and spironolactone showed a partial inhibition of the effects of angiotensin. In all the animals treated there was a clear correlation between systolic blood pressure and whole brain TH activity. The significance of these changes is discussed in the light of the central mechanism of hypertension."}
{"id": "PMID:8610", "title": "Correlation of behavioural inhibition or excitation produced by bromocriptine with changes in brain catecholamine turnover.", "content": "The dopamine agonist, bromocriptine, produced either inhibition or stimulation of motor behaviour in rats depending upon the dose and time after administration. Stimulation of motor activity occurred only with high doses after a 1-2 h delay. Both inhibition and stimulation were associated with decreased turnover of dopamine in the brain. Release of noradrenaline in brain and noradrenaline plus adrenaline in adrenal varied with motor activity. It is suggested that low doses of bromocriptine inhibit behaviour by activating an inhibitory presynaptic receptor, resulting in reduced synthesis and release of dopamine, whilst high doses cause behavioural excitation by activating the post-synaptic dopamine receptor.", "contents": "Correlation of behavioural inhibition or excitation produced by bromocriptine with changes in brain catecholamine turnover. The dopamine agonist, bromocriptine, produced either inhibition or stimulation of motor behaviour in rats depending upon the dose and time after administration. Stimulation of motor activity occurred only with high doses after a 1-2 h delay. Both inhibition and stimulation were associated with decreased turnover of dopamine in the brain. Release of noradrenaline in brain and noradrenaline plus adrenaline in adrenal varied with motor activity. It is suggested that low doses of bromocriptine inhibit behaviour by activating an inhibitory presynaptic receptor, resulting in reduced synthesis and release of dopamine, whilst high doses cause behavioural excitation by activating the post-synaptic dopamine receptor."}
{"id": "PMID:8611", "title": "Dopamine-sensitive adenylate cyclase in canine renal artery.", "content": "To characterize further a putative dopamine receptor in the renal artery, the effects of dopamine on canine renal artery adenylate cyclase activity were studied. Since the femoral artery is thought to be devoid of a similar dopamine receptor, the effects of dopamine on the adenylate cyclase activity of the canine femoral artery were also studied. In tissues from dogs with or without phenoxybenzamine pretreatment, renal artery adenylate cyclase was maximally stimulated by 4 muM dopamine, compared to 20 muM required for the femoral artery enzyme. The concentrations of isoprenaline required to maximally stimulate renal and femoral artery adenylate cyclase were 0-04 and 0-2 muM, respectively. In tissue from the phenoxybenzamine-pretreated dog, the sitmulatroy effect of dopamine on the renal artery enzyme was selectively blocked by 0-01 muM haloperidol, but not by 0-2 muM propranolol. In the femoral artery, however, the dopamine stimulation was blocked by both antagonists. Stimulation by isoprenaline of renal and femoral artery adenylate cyclase was blocked by propranolol. These data suggest the concept that dopamine interacts with a specific artery receptor apparently different from alpha-and beta-adrenoceptors.", "contents": "Dopamine-sensitive adenylate cyclase in canine renal artery. To characterize further a putative dopamine receptor in the renal artery, the effects of dopamine on canine renal artery adenylate cyclase activity were studied. Since the femoral artery is thought to be devoid of a similar dopamine receptor, the effects of dopamine on the adenylate cyclase activity of the canine femoral artery were also studied. In tissues from dogs with or without phenoxybenzamine pretreatment, renal artery adenylate cyclase was maximally stimulated by 4 muM dopamine, compared to 20 muM required for the femoral artery enzyme. The concentrations of isoprenaline required to maximally stimulate renal and femoral artery adenylate cyclase were 0-04 and 0-2 muM, respectively. In tissue from the phenoxybenzamine-pretreated dog, the sitmulatroy effect of dopamine on the renal artery enzyme was selectively blocked by 0-01 muM haloperidol, but not by 0-2 muM propranolol. In the femoral artery, however, the dopamine stimulation was blocked by both antagonists. Stimulation by isoprenaline of renal and femoral artery adenylate cyclase was blocked by propranolol. These data suggest the concept that dopamine interacts with a specific artery receptor apparently different from alpha-and beta-adrenoceptors."}
{"id": "PMID:8612", "title": "A four parameter model for oral drug absorption.", "content": "A method has been developed for assessing absorption parameters from plasma concentration-time results taken over a relatively short time period. In this method, the disposition function is simplified so as to reduce the number of parameters to be evaluated from the five of the two compartment disposition equation of four, and to avoid the requirement for the evaluation of a slow disposition rate constant. The measurments need not therefore be continued over a period long after absorption is complete. A suitable design for kinetic experiments using this method for interpreting the results, is described. A random noise statistical method is proposed for assessing the stability of the calculated parameters.", "contents": "A four parameter model for oral drug absorption. A method has been developed for assessing absorption parameters from plasma concentration-time results taken over a relatively short time period. In this method, the disposition function is simplified so as to reduce the number of parameters to be evaluated from the five of the two compartment disposition equation of four, and to avoid the requirement for the evaluation of a slow disposition rate constant. The measurments need not therefore be continued over a period long after absorption is complete. A suitable design for kinetic experiments using this method for interpreting the results, is described. A random noise statistical method is proposed for assessing the stability of the calculated parameters."}
{"id": "PMID:8624", "title": "Carbon-13 magnetic resonance spectroscopy of drugs II: antihistamines.", "content": "The natural abundance carbon-13 magnetic resonance spectra of a series of antihistamines (pheniramine, chlorpheniramine, methapyrilene, tripelennamine, pyrilamine, and thonzylamine) were detemined using the pulse Fourier transform technique. The chemical shifts were assigned with the aid of long-range carbon-13-hydrogen coupling constants.", "contents": "Carbon-13 magnetic resonance spectroscopy of drugs II: antihistamines. The natural abundance carbon-13 magnetic resonance spectra of a series of antihistamines (pheniramine, chlorpheniramine, methapyrilene, tripelennamine, pyrilamine, and thonzylamine) were detemined using the pulse Fourier transform technique. The chemical shifts were assigned with the aid of long-range carbon-13-hydrogen coupling constants."}
{"id": "PMID:8625", "title": "Ionization constants of cephalosporin zwitterionic compounds.", "content": "The microionization constants for two zwitterionic compounds were determined by incorporating two experimental techniques. These compounds have chromophoric changes dependent upon the solution pH. By combining the spectrophotometric measurements with potentiometric mmeasurements, all four microionization constants were calculated. The method used is completely general and is applicable to all diprotic compounds that exhibit this spectrophotometric behavior. The observed pKa's had differences of at most 1.2 units for either compound and were in the 1-4 range. A comparison of the results with each compound and similar compounds indicates that the values are resonable.", "contents": "Ionization constants of cephalosporin zwitterionic compounds. The microionization constants for two zwitterionic compounds were determined by incorporating two experimental techniques. These compounds have chromophoric changes dependent upon the solution pH. By combining the spectrophotometric measurements with potentiometric mmeasurements, all four microionization constants were calculated. The method used is completely general and is applicable to all diprotic compounds that exhibit this spectrophotometric behavior. The observed pKa's had differences of at most 1.2 units for either compound and were in the 1-4 range. A comparison of the results with each compound and similar compounds indicates that the values are resonable."}
{"id": "PMID:8626", "title": "Correlation of in vitro and in vivo methodology for evaluation of antacids.", "content": "The rate and extent of acid consumption of an antacid suspension and tablet were evaluated by in vitro and in vivo techniques. Four different test procedures were used to estimate in vitro antacid reactivity. In vivo effects were determined in the fasted and postcibal states in normal human subjects by a radiotelemetry procedure. The duration of elevation of intragastric pH greater than 3 was in agreement with in vitro estimates of total acid consumption of the antacid. There was also good correlation between onset, extent, and duration of in vivo antacid activity and a modified in vitro Beekman antacid test procedure. There was no significant difference in antacid activity of the tablet or suspension in either in vitro or in vivo test procedures. A wide variation in antacid activity was observed between subjects and also in the fasted versus postcibal states. These studies emphasize the requirements for standardization of antacid products by comparactive in vitro and in vivo evaluations to facilitate individualized dose titration  of the antacid in each patient and correlation of the acid secretion rate in various types of GI disease with the antacid dose.", "contents": "Correlation of in vitro and in vivo methodology for evaluation of antacids. The rate and extent of acid consumption of an antacid suspension and tablet were evaluated by in vitro and in vivo techniques. Four different test procedures were used to estimate in vitro antacid reactivity. In vivo effects were determined in the fasted and postcibal states in normal human subjects by a radiotelemetry procedure. The duration of elevation of intragastric pH greater than 3 was in agreement with in vitro estimates of total acid consumption of the antacid. There was also good correlation between onset, extent, and duration of in vivo antacid activity and a modified in vitro Beekman antacid test procedure. There was no significant difference in antacid activity of the tablet or suspension in either in vitro or in vivo test procedures. A wide variation in antacid activity was observed between subjects and also in the fasted versus postcibal states. These studies emphasize the requirements for standardization of antacid products by comparactive in vitro and in vivo evaluations to facilitate individualized dose titration  of the antacid in each patient and correlation of the acid secretion rate in various types of GI disease with the antacid dose."}
{"id": "PMID:8627", "title": "Effect of solvent on tetrazolium reaction.", "content": "The rate of color development of a tetrazolium formazan is shown to be inversely proportional to the dielectric constant of the solvent medium and directly proportional to the hydrogen-bonding capability of solvent mixtures having the same dielectric constant. The geometric isomers of the formazans have different absorbance maxima, and the wavelength of maximum absorbance of a mixture of formazans in different solvents depends upon which isomer predominates in that solvent. The trans-syn-isomer (blue form) of blue tetrazolium has a maximum absorbance at 625 nm in dimethylformamide while the trans-anti-isomer (red form) absorbs at 517 nm in methanol. The absorbance maxima of the corresponding isomers of the formazans of triphenyltetrazolium occur at 535 and 485 nm, respectively. Water and/or methanol (to a lesser extent) are important in the stabilization of the trans-anti-isomer, since the small size of these two substances allows them to form strong intermolecular hydrogen bonds with one or both nitrogen atoms of the azo linkage, thereby preventing the formation of the intramolecular hydrogen bonding exhibited by the trans-syn-isomer. The formazan produced by the reaction of corticosteroids with tetrazolium in strongly basic media can lose a reduction unit and be reoxidized to the tetrazolium. This reaction is solvent dependent and occurs at a much faster rate in chloroform than in alcohol USP.", "contents": "Effect of solvent on tetrazolium reaction. The rate of color development of a tetrazolium formazan is shown to be inversely proportional to the dielectric constant of the solvent medium and directly proportional to the hydrogen-bonding capability of solvent mixtures having the same dielectric constant. The geometric isomers of the formazans have different absorbance maxima, and the wavelength of maximum absorbance of a mixture of formazans in different solvents depends upon which isomer predominates in that solvent. The trans-syn-isomer (blue form) of blue tetrazolium has a maximum absorbance at 625 nm in dimethylformamide while the trans-anti-isomer (red form) absorbs at 517 nm in methanol. The absorbance maxima of the corresponding isomers of the formazans of triphenyltetrazolium occur at 535 and 485 nm, respectively. Water and/or methanol (to a lesser extent) are important in the stabilization of the trans-anti-isomer, since the small size of these two substances allows them to form strong intermolecular hydrogen bonds with one or both nitrogen atoms of the azo linkage, thereby preventing the formation of the intramolecular hydrogen bonding exhibited by the trans-syn-isomer. The formazan produced by the reaction of corticosteroids with tetrazolium in strongly basic media can lose a reduction unit and be reoxidized to the tetrazolium. This reaction is solvent dependent and occurs at a much faster rate in chloroform than in alcohol USP."}
{"id": "PMID:8628", "title": "Aggregation of antihistamines in aqueous solution: effect of counterions on self-association of pyridine derivatives.", "content": "The effects of electrolytes on the self-association of the antihistaminic drugs, tripelennamine hydrochloride, thenyldiamine hydrochloride, pyrilamine maleate, pheniramine maleate, chlorpheniramine maleate, and brompheniramine maleate, in aqueous solution were examined by light-scattering from tripelennamine bydrochloride and thenyldiamine hydrochloride in 0.154 mole of sodium chloride/kg and 0.150 mole of sodium maleate/kg indicated a micellar pattern of aggregation. Higher aggregation numbers and lower CMC's were determined in the presence of the maleate ion. No significant discontinuity in the concentration dependence of the light scattering of the remaining compounds in either of the two electrolytes was evident, and the aggregation of these compounds was treated using a stepwise association model. Values of the association constants and the limiting number of associating species were, in general, increased by the addition of electrolyte in the order water less than sodium chloride less than sodium maleate. An apparently nonmicellar pattern of aggregation could be induced by chemically changing the counterion from chloride to maleate.", "contents": "Aggregation of antihistamines in aqueous solution: effect of counterions on self-association of pyridine derivatives. The effects of electrolytes on the self-association of the antihistaminic drugs, tripelennamine hydrochloride, thenyldiamine hydrochloride, pyrilamine maleate, pheniramine maleate, chlorpheniramine maleate, and brompheniramine maleate, in aqueous solution were examined by light-scattering from tripelennamine bydrochloride and thenyldiamine hydrochloride in 0.154 mole of sodium chloride/kg and 0.150 mole of sodium maleate/kg indicated a micellar pattern of aggregation. Higher aggregation numbers and lower CMC's were determined in the presence of the maleate ion. No significant discontinuity in the concentration dependence of the light scattering of the remaining compounds in either of the two electrolytes was evident, and the aggregation of these compounds was treated using a stepwise association model. Values of the association constants and the limiting number of associating species were, in general, increased by the addition of electrolyte in the order water less than sodium chloride less than sodium maleate. An apparently nonmicellar pattern of aggregation could be induced by chemically changing the counterion from chloride to maleate."}
{"id": "PMID:8629", "title": "Enthalpies of hydrogen bonding in psychotropic drugs.", "content": "The enthalpy of hydrogen bonding of some antipsychotic, antidepressant, anticonvulsant, and antianxiety agents with phenol, as determined from IR and NMR spectroscopic measurements, was shown not to be responsible for differences in activity within the drug classes. These results support a theoretical prediction advanced for anticonvulsant activity.", "contents": "Enthalpies of hydrogen bonding in psychotropic drugs. The enthalpy of hydrogen bonding of some antipsychotic, antidepressant, anticonvulsant, and antianxiety agents with phenol, as determined from IR and NMR spectroscopic measurements, was shown not to be responsible for differences in activity within the drug classes. These results support a theoretical prediction advanced for anticonvulsant activity."}
{"id": "PMID:8630", "title": "Synthesis, physicochemical parameters, and in vitro evaluation of N1-p-chlorophenyl-N5-alkylbiguanides.", "content": "A series of N1-p-chlorophenyl-N5-alkylbiguanides were synthesized as potential inhibitors of dental plaque. Partition coefficients and pKa values were determined by standard methods. Biological activity was evaluated against Streptococcus mutans, a pure strain of plaque-forming bacteria. All compounds were compared to chlorhexidine acetate.", "contents": "Synthesis, physicochemical parameters, and in vitro evaluation of N1-p-chlorophenyl-N5-alkylbiguanides. A series of N1-p-chlorophenyl-N5-alkylbiguanides were synthesized as potential inhibitors of dental plaque. Partition coefficients and pKa values were determined by standard methods. Biological activity was evaluated against Streptococcus mutans, a pure strain of plaque-forming bacteria. All compounds were compared to chlorhexidine acetate."}
{"id": "PMID:8633", "title": "A quantitative study of metiamide, a histamine H2-antagonist, on the isolated whole rat stomach.", "content": "1. An isolated whole stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2. The mean basal acid secretion before stimulation was 4-19 +/- 0-31 X 10 (-8) mol min-1. Metiamide did not significantly reduce this spontaneous secretion. 3. The preparation gave dose-dependent responses to histomine (10(-5)-10(-4)M) which were readily reversed on washing. 4. The effect of metiamide on histamine-stimulated acid secretion was investigated. Metamide, at doses of 3 X 10(-6)M, and 3 X 10(-5)M, caused a parallel displacement of the histamine dose-response curve, indicating competitive antagonism. These dose-response curves were used to calculate dose ratios (DR) for metiamide. 5. A plot of log10 (DR - 1) against log 10 [antagonist] gave a pA2 value for metiamide of 5-91.", "contents": "A quantitative study of metiamide, a histamine H2-antagonist, on the isolated whole rat stomach. 1. An isolated whole stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2. The mean basal acid secretion before stimulation was 4-19 +/- 0-31 X 10 (-8) mol min-1. Metiamide did not significantly reduce this spontaneous secretion. 3. The preparation gave dose-dependent responses to histomine (10(-5)-10(-4)M) which were readily reversed on washing. 4. The effect of metiamide on histamine-stimulated acid secretion was investigated. Metamide, at doses of 3 X 10(-6)M, and 3 X 10(-5)M, caused a parallel displacement of the histamine dose-response curve, indicating competitive antagonism. These dose-response curves were used to calculate dose ratios (DR) for metiamide. 5. A plot of log10 (DR - 1) against log 10 [antagonist] gave a pA2 value for metiamide of 5-91."}
{"id": "PMID:8634", "title": "Evidence that brain prostaglandin synthesis is not essential in fever.", "content": "1. We have tested the hypothesis that a fever caused by pyrogen depends upon the synthesis of prostaglandin E in the brain and that the prostaglandin in turn acts on the hypothalamus to produce fever. 2. In rabbits, fever was produced by the injection of leucocyte pyrogen in a lateral cerebral ventricle. The latency, rate of rise and magnitude of the fever was unaffected by the simultaneous intraventricular injection of two prostaglandin antagonists, SC 19220 and HR 546. 3. Both antagonists effectively attenuated the fever caused by the intraventricular injection of prostaglandin E2. 4. This evidence is not consistent with the hypothesis that prostaglandin E is the principal mediator of fever.", "contents": "Evidence that brain prostaglandin synthesis is not essential in fever. 1. We have tested the hypothesis that a fever caused by pyrogen depends upon the synthesis of prostaglandin E in the brain and that the prostaglandin in turn acts on the hypothalamus to produce fever. 2. In rabbits, fever was produced by the injection of leucocyte pyrogen in a lateral cerebral ventricle. The latency, rate of rise and magnitude of the fever was unaffected by the simultaneous intraventricular injection of two prostaglandin antagonists, SC 19220 and HR 546. 3. Both antagonists effectively attenuated the fever caused by the intraventricular injection of prostaglandin E2. 4. This evidence is not consistent with the hypothesis that prostaglandin E is the principal mediator of fever."}
{"id": "PMID:8636", "title": "Non-uniform probabilities of quantal release at the crayfish neuromuscular junction.", "content": "1. Transmitter release at the neuromuscular junction of the crayfish walking leg has been found to deviate from binomial predictions immediately after the onset of repetitive stimulation of the presynaptic nerve at frequencies of at least 15 Hz. 2. After several minutes of continuous stimulation, and at lower rates of stimulation, however, the number of quanta released could be described quite well by binomial or Poisson statistics. 3. Deviations from the theoretical expectations were characterized by (a) fewer release failures than predicted, (b) occasions in which the number of quanta released was more than the estimated number of quanta available for release, and (c) a tendency for the data to be underdispersed. 4. Each of these three characteristics are consistent with the hypothesis that different releasable quanta may have different probabilities of responding to a nerve impulse. 5. Using two different methods, different values of the non-uniform probabilities were estimated from the data. At each synaptic site at least one of the estimated probabilities was very high. 6. The need for caution in interpreting statistical description of quantal release is emphasized.", "contents": "Non-uniform probabilities of quantal release at the crayfish neuromuscular junction. 1. Transmitter release at the neuromuscular junction of the crayfish walking leg has been found to deviate from binomial predictions immediately after the onset of repetitive stimulation of the presynaptic nerve at frequencies of at least 15 Hz. 2. After several minutes of continuous stimulation, and at lower rates of stimulation, however, the number of quanta released could be described quite well by binomial or Poisson statistics. 3. Deviations from the theoretical expectations were characterized by (a) fewer release failures than predicted, (b) occasions in which the number of quanta released was more than the estimated number of quanta available for release, and (c) a tendency for the data to be underdispersed. 4. Each of these three characteristics are consistent with the hypothesis that different releasable quanta may have different probabilities of responding to a nerve impulse. 5. Using two different methods, different values of the non-uniform probabilities were estimated from the data. At each synaptic site at least one of the estimated probabilities was very high. 6. The need for caution in interpreting statistical description of quantal release is emphasized."}
{"id": "PMID:8637", "title": "Caudate stimulation and substantia nigra activity in the rat.", "content": "1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed.", "contents": "Caudate stimulation and substantia nigra activity in the rat. 1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed."}
{"id": "PMID:8639", "title": "Eye protection from light radiation.", "content": "It appears that green absorptive lenses are highly desirable for the purposes of shielding the eyes against light radiation from molten metal during the casting and soldering procedures. The dental laboratory technicians have experienced no after-images, less eye fatigue, and no adverse symptoms when using these lenses, as were reported previously. The lenses not only effectively protect the eyes from the injurious light wavelengths, but they also provide for enough normal (as well as individually corrected) vision to accomplish any procedure necessary in the dental laboratory. We propose that the green absorptive lenses, with individual corrections if needed, be considered for dental laboratory technicians during dental laboratory procedures when needed, such as during casting and soldering, to protect their eyes from light radiation.", "contents": "Eye protection from light radiation. It appears that green absorptive lenses are highly desirable for the purposes of shielding the eyes against light radiation from molten metal during the casting and soldering procedures. The dental laboratory technicians have experienced no after-images, less eye fatigue, and no adverse symptoms when using these lenses, as were reported previously. The lenses not only effectively protect the eyes from the injurious light wavelengths, but they also provide for enough normal (as well as individually corrected) vision to accomplish any procedure necessary in the dental laboratory. We propose that the green absorptive lenses, with individual corrections if needed, be considered for dental laboratory technicians during dental laboratory procedures when needed, such as during casting and soldering, to protect their eyes from light radiation."}
{"id": "PMID:8644", "title": "Giant cell arteritis in general practice.", "content": "The clinical syndrome of polymyalgia rheumatica is reviewed. The relationship of this disease with temporal arteritis is discussed, and I consider both syndromes have a pathological basis of generalised giant cell arteritis.Seven cases of polymyalgia and four cases of temporal arteritis were recorded during the six-year period (1969-1975) in one general practice.The outlines of management are discussed, with a plea for earlier recognition of the syndromes of polymyalgia rheumatica and temporal arteritis in general practice.", "contents": "Giant cell arteritis in general practice. The clinical syndrome of polymyalgia rheumatica is reviewed. The relationship of this disease with temporal arteritis is discussed, and I consider both syndromes have a pathological basis of generalised giant cell arteritis.Seven cases of polymyalgia and four cases of temporal arteritis were recorded during the six-year period (1969-1975) in one general practice.The outlines of management are discussed, with a plea for earlier recognition of the syndromes of polymyalgia rheumatica and temporal arteritis in general practice."}
{"id": "PMID:8643", "title": "[Arteriography in polyarteritis nodosa. 15 cases (author's transl)].", "content": "Despite its imperfections, arteriography, when it demonstrates aneurysms, is an important element in diagnosis in all those cases in which histological findings are not definitive. It should be carried out before renal biopsy, given the risk of traumatic rupture of a possible aneurysm. The discovery of isolated distal arterial stenoses is not characteristic, though in the presence of a suggestive clinical picture, amy be considered as an argument in favour of the diagnosis. They occur frequently in the arteries of the digestive tract even in the absence of any abdominal symptoms or signs. Arteriography also has a prognostic value in establishing the extent of arterial lesions and, finally, is useful in the diagnosis of certain complications such as visceral haematomas and digestive haemorrhages. We thus feel that polyarteritis nodosa should be the object of a complete vascular exploration, including aortography with selective renal studies but also coelio-mesenteric opacification. In the light of the clinical context, the distal limb arteries may also be explored. Thus the diagnosis of polyarteritis nodosa is not purely histological but also arteriographic.", "contents": "[Arteriography in polyarteritis nodosa. 15 cases (author's transl)]. Despite its imperfections, arteriography, when it demonstrates aneurysms, is an important element in diagnosis in all those cases in which histological findings are not definitive. It should be carried out before renal biopsy, given the risk of traumatic rupture of a possible aneurysm. The discovery of isolated distal arterial stenoses is not characteristic, though in the presence of a suggestive clinical picture, amy be considered as an argument in favour of the diagnosis. They occur frequently in the arteries of the digestive tract even in the absence of any abdominal symptoms or signs. Arteriography also has a prognostic value in establishing the extent of arterial lesions and, finally, is useful in the diagnosis of certain complications such as visceral haematomas and digestive haemorrhages. We thus feel that polyarteritis nodosa should be the object of a complete vascular exploration, including aortography with selective renal studies but also coelio-mesenteric opacification. In the light of the clinical context, the distal limb arteries may also be explored. Thus the diagnosis of polyarteritis nodosa is not purely histological but also arteriographic."}
{"id": "PMID:8646", "title": "Bifidobacteria in the intestinal tract of infants: an in-vivo study.", "content": "Weekly faecal specimens from 18 babies were examined during the first 8 weeks of life. Eight infants were breast fed, ten were bottle-fed. All suckling infants received supplementary feeds for the first 8 days. A buffer consisting of acetic acid and acetate was demonstrated in the faeces of all the breast-fed infants at some time during the period of examination. This buffer was rarely detected during the 1st week of life when supplementary feeds were given, and buffer already present gradually disappeared with the introduction of mixed feeding. In contrast, at no time was an acetate buffer demonstrated in the faeces of bottle-fed infants. Babies receiving breast milk produced faeces with low pH, high counts of saccharolytic organisms including bifidobacteria and Streptococcus faecium, and low counts of Escherichia coli, bacteroides and clostridia. Bottle-fed infants on the other hand produced faeces with a high pH and high counts of E. coli and putrefactive bacteria, but with low counts of bifidobacteria.", "contents": "Bifidobacteria in the intestinal tract of infants: an in-vivo study. Weekly faecal specimens from 18 babies were examined during the first 8 weeks of life. Eight infants were breast fed, ten were bottle-fed. All suckling infants received supplementary feeds for the first 8 days. A buffer consisting of acetic acid and acetate was demonstrated in the faeces of all the breast-fed infants at some time during the period of examination. This buffer was rarely detected during the 1st week of life when supplementary feeds were given, and buffer already present gradually disappeared with the introduction of mixed feeding. In contrast, at no time was an acetate buffer demonstrated in the faeces of bottle-fed infants. Babies receiving breast milk produced faeces with low pH, high counts of saccharolytic organisms including bifidobacteria and Streptococcus faecium, and low counts of Escherichia coli, bacteroides and clostridia. Bottle-fed infants on the other hand produced faeces with a high pH and high counts of E. coli and putrefactive bacteria, but with low counts of bifidobacteria."}
{"id": "PMID:8647", "title": "Bifidobacteria in the intestinal tract of infants: an in-vitro study.", "content": "In-vitro studies showed that a number of factors are likely to influence the production and maintenance of a bifidobacillary flora and low pH in the faeces of newborn infants. Considerable importance is attached to the nature of the end products of bacterial metabolism in the large intestine. Thus, there is evidence to suggest that acetic acid and other metabolites of intraluminal bacterial growth suppress the growth of gram-negative organisms, but are without effect upon that of bifidobacteria. This mechanism in turn is controlled by the nature of the feed; important factors in breast milk include high lactose, low protein and low phosphate content.", "contents": "Bifidobacteria in the intestinal tract of infants: an in-vitro study. In-vitro studies showed that a number of factors are likely to influence the production and maintenance of a bifidobacillary flora and low pH in the faeces of newborn infants. Considerable importance is attached to the nature of the end products of bacterial metabolism in the large intestine. Thus, there is evidence to suggest that acetic acid and other metabolites of intraluminal bacterial growth suppress the growth of gram-negative organisms, but are without effect upon that of bifidobacteria. This mechanism in turn is controlled by the nature of the feed; important factors in breast milk include high lactose, low protein and low phosphate content."}
{"id": "PMID:8649", "title": "Post-traumatic hepatic dysfunction as a major etiology in post-traumatic jaundice.", "content": "Thirty-eight patients who had sustained acute trauma, profound hemorrhagic shock, and massive transfusion were studied prospectively to determine the predominant etiologic factors in the development of post-traumatic jaundice. An analysis of clinical and biochemical factors occurring in association with each bilirubin peak in the postoperative course found the jaundice related to transfusion and surgery in 11 instances, to sepsis and septicemia in 15 instances, and to hepatic dysfunction in 23 instances. Results indicated that admission estimates of SGOT and LDH levels, the height of the bilirubin peak and the postoperative day on which it occurs, and the white cell count and GGT at the time of the peak may be of use in the differential diagnosis. Four case reports were used to emphasize the fluctuating pattern of jaundice and the different etiologic factors that may predominate. Light and electron microscopy from three patients illustrated the structural alterations that accompany the biochemical impairment of liver function and enable a more precise appreciation of this syndrome. Hepatic dysfunction appears to be implicated in a high proportion of patients who develop post-traumatic jaundice, which frequently occurs as part of a spectrum of multiple organ failure.", "contents": "Post-traumatic hepatic dysfunction as a major etiology in post-traumatic jaundice. Thirty-eight patients who had sustained acute trauma, profound hemorrhagic shock, and massive transfusion were studied prospectively to determine the predominant etiologic factors in the development of post-traumatic jaundice. An analysis of clinical and biochemical factors occurring in association with each bilirubin peak in the postoperative course found the jaundice related to transfusion and surgery in 11 instances, to sepsis and septicemia in 15 instances, and to hepatic dysfunction in 23 instances. Results indicated that admission estimates of SGOT and LDH levels, the height of the bilirubin peak and the postoperative day on which it occurs, and the white cell count and GGT at the time of the peak may be of use in the differential diagnosis. Four case reports were used to emphasize the fluctuating pattern of jaundice and the different etiologic factors that may predominate. Light and electron microscopy from three patients illustrated the structural alterations that accompany the biochemical impairment of liver function and enable a more precise appreciation of this syndrome. Hepatic dysfunction appears to be implicated in a high proportion of patients who develop post-traumatic jaundice, which frequently occurs as part of a spectrum of multiple organ failure."}
{"id": "PMID:8650", "title": "Bacterial infection and the asplenic host: a review.", "content": "The risk of bacterial sepsis in the surgically or functionally asplenic host is reviewed. The lowest morbidity occurs in patients splenectomized because of trauma to the spleen; the highest morbidity occurs in patients splenectomized for thalassemia. There is approximately a 50% mortality associated with sepsis secondary to asplenia and the pneumococcus is responsible for over 50% of the cases. Normal spleen function and alteration in host defense occurring as a consequence of asplenia is discussed. Finally, alternatives to and indications for splenectomy as well as prophylactic measures are considered. It is concluded that, at the present time, antibiotic coverage for an indefinite period of time may be indicated for surgically or functionally asplenic patients.", "contents": "Bacterial infection and the asplenic host: a review. The risk of bacterial sepsis in the surgically or functionally asplenic host is reviewed. The lowest morbidity occurs in patients splenectomized because of trauma to the spleen; the highest morbidity occurs in patients splenectomized for thalassemia. There is approximately a 50% mortality associated with sepsis secondary to asplenia and the pneumococcus is responsible for over 50% of the cases. Normal spleen function and alteration in host defense occurring as a consequence of asplenia is discussed. Finally, alternatives to and indications for splenectomy as well as prophylactic measures are considered. It is concluded that, at the present time, antibiotic coverage for an indefinite period of time may be indicated for surgically or functionally asplenic patients."}
{"id": "PMID:8651", "title": "Some biological and physical properties of molluscum contagiosum virus propagated in cell culture.", "content": "Molluscum contagiosum virus propagated in FL cells of human amnion origin has a one-step growth cycle time of 12 to 14 h. The appearance and exponential increase of intracellular virus preceded the release of extracellular virus by approximately 2 h. Demonstration of comparable titers of extracellular and intracellular virus at the end of the replication cycle indicated that a substantial amount of virus remained associated with cells exhibiting cytopathogenic changes. Mean buoyant density values of virus in sucrose ranged from 1.275 to 1.278 g/cm3, but in CsCl the virus banded at densities at 1.325 to 1.340 and 1.261 to 1.281 g/cm3. Although virus infectivity was not affected by high concentrations of CsCl, it was found by polyacrylamide gel electrophoresis that the salt removed several nonglycosylated polypeptides with estimated molecular weights of 15,000 to 60,000. This suggested that the high-density band (1.325 to 1.340) may reflect the loss of these structural components. The half-life of virus infectivity was approximately 26.5 h at 26 degrees C and 11.2 h at 37 degrees C. Although the virus was rapidly inactivated at 50 degrees C, it could be stabilized at this temperature by the presence of 1.0 M MgCl2. Virus did not agglutinate newborn chick, adult chicken, or type \"0\" human erythrocytes. Virus infectivity was found to be sensitive to acid pH but resistant to treatment with diethyl ether or chloroform. The replication of molluscum virus in FL cells was not inhibited by 5-iodo-2'-deoxyuridine, 5-bromo-2'-deoxyuridine, or cytosine arabinonucleoside in noncytotoxic concentrations of 200 to 400 mug/ml, but greater than 99% reduction in the yield of herpes simplex virus or vaccinia virus in FL cells was obtained with 200 mug of these compounds per ml. Guanidinium chloride in concentrations of 100 to 200 mug/ml reduced molluscum virus yields by more than 99.9%.", "contents": "Some biological and physical properties of molluscum contagiosum virus propagated in cell culture. Molluscum contagiosum virus propagated in FL cells of human amnion origin has a one-step growth cycle time of 12 to 14 h. The appearance and exponential increase of intracellular virus preceded the release of extracellular virus by approximately 2 h. Demonstration of comparable titers of extracellular and intracellular virus at the end of the replication cycle indicated that a substantial amount of virus remained associated with cells exhibiting cytopathogenic changes. Mean buoyant density values of virus in sucrose ranged from 1.275 to 1.278 g/cm3, but in CsCl the virus banded at densities at 1.325 to 1.340 and 1.261 to 1.281 g/cm3. Although virus infectivity was not affected by high concentrations of CsCl, it was found by polyacrylamide gel electrophoresis that the salt removed several nonglycosylated polypeptides with estimated molecular weights of 15,000 to 60,000. This suggested that the high-density band (1.325 to 1.340) may reflect the loss of these structural components. The half-life of virus infectivity was approximately 26.5 h at 26 degrees C and 11.2 h at 37 degrees C. Although the virus was rapidly inactivated at 50 degrees C, it could be stabilized at this temperature by the presence of 1.0 M MgCl2. Virus did not agglutinate newborn chick, adult chicken, or type \"0\" human erythrocytes. Virus infectivity was found to be sensitive to acid pH but resistant to treatment with diethyl ether or chloroform. The replication of molluscum virus in FL cells was not inhibited by 5-iodo-2'-deoxyuridine, 5-bromo-2'-deoxyuridine, or cytosine arabinonucleoside in noncytotoxic concentrations of 200 to 400 mug/ml, but greater than 99% reduction in the yield of herpes simplex virus or vaccinia virus in FL cells was obtained with 200 mug of these compounds per ml. Guanidinium chloride in concentrations of 100 to 200 mug/ml reduced molluscum virus yields by more than 99.9%."}
{"id": "PMID:8652", "title": "Characterization of some pneumococcal bacteriophages.", "content": "The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 X 10(10) to 4 X 10(10) PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages omega3 and omega8 each have linear double-stranded DNA of 33 X 10(6) daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol%, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, omega3 and omega8 have D37 values of 33 and 55 J/m2, respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between omega3 and omega8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages.", "contents": "Characterization of some pneumococcal bacteriophages. The growth of pneumococcal phages at high cell and phage densities is enhanced strongly by the substitution of potassium for sodium in the medium. Initial titers of 2 X 10(10) to 4 X 10(10) PFU/ml are readily obtained, and concentrated stocks are stable in a storage buffer described here. The mechanism of the cation effect is obscure. Phages omega3 and omega8 each have linear double-stranded DNA of 33 X 10(6) daltons per particle, with an apparent guanine plus cytosine content of 47 to 49 mol%, as determined by buoyancy and melting temperature, but with an unusual absorbance spectrum. Efficiency of plating is high if sufficient time is allowed for a relatively slow adsorption, which differs several-fold in rate between the two phages. Morphologically, these and other pneumococcal phages are similar to coliphage lambda but with a longer tail and tail fiber. Upon UV inactivation, omega3 and omega8 have D37 values of 33 and 55 J/m2, respectively, and each shows multiplicity reactivation. A total of 13 ts mutants have been isolated from the two phages, representing only two complementation groups; complementation and recombination occur between omega3 and omega8 mutants. Both phages provoke high-titer antisera with extensive cross-reactivity against a number of newly isolated pneumococcal phages."}
{"id": "PMID:8659", "title": "Mechanism of action of some bitter-tasting compounds on frog taste cells.", "content": "Effects of some bitter-tasting compounds on frog taste receptors were examined by recording glossopharyngeal nerve responses. The order of effectiveness of the compounds was quinine greater than brucine greater than formanilide greater than caffeine greater than urea. When the effects of quinine, brucine and caffeine on electrical responses in taste cells were examined, they all produced a depolarization associated with an increased input resistance. The action of the three compounds on taste receptors therefore, operates with a similar mechanism. The electrical responses in cells, produced by quinine, progressed slowly with time. Such effects with quinine are similar to those with procaine. After adaptation to quinine, the nerve responses to various chemical stimuli were gradually reduced in magnitude, while the electrical responses in taste cells during stimulation by chemicals became smaller. The mechanism of the effects of bitter stimuli are discussed in light of recent findings on the interaction of bitter stimuli with lipid monolayers and the extraction of lipid from bovine taste papillae by bitter stimuli.", "contents": "Mechanism of action of some bitter-tasting compounds on frog taste cells. Effects of some bitter-tasting compounds on frog taste receptors were examined by recording glossopharyngeal nerve responses. The order of effectiveness of the compounds was quinine greater than brucine greater than formanilide greater than caffeine greater than urea. When the effects of quinine, brucine and caffeine on electrical responses in taste cells were examined, they all produced a depolarization associated with an increased input resistance. The action of the three compounds on taste receptors therefore, operates with a similar mechanism. The electrical responses in cells, produced by quinine, progressed slowly with time. Such effects with quinine are similar to those with procaine. After adaptation to quinine, the nerve responses to various chemical stimuli were gradually reduced in magnitude, while the electrical responses in taste cells during stimulation by chemicals became smaller. The mechanism of the effects of bitter stimuli are discussed in light of recent findings on the interaction of bitter stimuli with lipid monolayers and the extraction of lipid from bovine taste papillae by bitter stimuli."}
{"id": "PMID:8660", "title": "Evidences for alpha excitatory action of catecholamines on the electrical activity of the guinea-pig stomach.", "content": "Effects of catecholamines and their inhibitors on the electrical activity of the smooth muscle of the guinea-pig stomach were studied by using pressure electrodes. The spontaneous electrical activity of antrum and corpus preparations consisted of slow waves with or without superimposed spikes. In quiescent fundus preparations, the spike activity and slow waves were generated by TEA. Catecholamines (noradrenaline, isoprenaline and adrenaline) suppressed or blocked the spike discharges and the generation of slow waves. However, the spike activity was enhanced at a higher concentration of phenylephrine in the antrumand fundus preparations. Inhibitory responses of the smooth muscles from whole regions to adrenaline, noradrenaline or isoprenaline were antagonized by propranolol or DCI but not by phentolamine or phenoxybenzamine. Therefore, inhibitory actions of these amines appear to involve beta-adrenoceptors. After treatment with tetrodotoxin, noradrenaline and isoprenaline blocked the spike activity and the generation of slow waves. Phenylephrine or adrenaline potentiated the spike activity in the presence of tetrodotoxin. After treatment with DCI or propranolol, phenylephrine potentiated the spike activity of the antrum and fundus preparations. These excitatory effects were antagonized by phentolamine or phenoxybenzamine. It is concluded that excitatory actions of these amines are mediated by alpha-adrenoceptors rather than via a nervous pathway.", "contents": "Evidences for alpha excitatory action of catecholamines on the electrical activity of the guinea-pig stomach. Effects of catecholamines and their inhibitors on the electrical activity of the smooth muscle of the guinea-pig stomach were studied by using pressure electrodes. The spontaneous electrical activity of antrum and corpus preparations consisted of slow waves with or without superimposed spikes. In quiescent fundus preparations, the spike activity and slow waves were generated by TEA. Catecholamines (noradrenaline, isoprenaline and adrenaline) suppressed or blocked the spike discharges and the generation of slow waves. However, the spike activity was enhanced at a higher concentration of phenylephrine in the antrumand fundus preparations. Inhibitory responses of the smooth muscles from whole regions to adrenaline, noradrenaline or isoprenaline were antagonized by propranolol or DCI but not by phentolamine or phenoxybenzamine. Therefore, inhibitory actions of these amines appear to involve beta-adrenoceptors. After treatment with tetrodotoxin, noradrenaline and isoprenaline blocked the spike activity and the generation of slow waves. Phenylephrine or adrenaline potentiated the spike activity in the presence of tetrodotoxin. After treatment with DCI or propranolol, phenylephrine potentiated the spike activity of the antrum and fundus preparations. These excitatory effects were antagonized by phentolamine or phenoxybenzamine. It is concluded that excitatory actions of these amines are mediated by alpha-adrenoceptors rather than via a nervous pathway."}
{"id": "PMID:8661", "title": "The electrogenesis of adrenaline-hyperpolarization of sympathetic ganglion cells in bullfrogs.", "content": "Bullfrog sympathetic ganglion cells produced hyperpolarizing (Ad-hyperpolarization) and depolarizing (Ad-depolarization) responses when adrenaline (Ad) was directly applied to ganglia. The nature of Ad-hyperpolarization recorded by the sucrose-gap method was analysed in the present experiment, in order to clarify its electrogenesis. The amplitude of Ad-hyperpolarization was increased or decreased while ganglion cell membranes were hyperpolarized or depolarized, respectively, by applying a moderate conditioning current to the ganglia. The Ad-hyperpolarization was depressed in K+-rich solutions as well as in K+-deficient solutions. It was not significantly altered by replacing the extracellular total Cl ions by equimolar glutamate or thiosulfate ions. Ad-hyperpolarization was depressed and finally abolished in the Na+-free Tris solution, and was reversibly eliminated in the solution where Na ions were totally replaced by equimolar Li ions. It was enhanced when a preparation was previously perfused in the K+-free, Na+-rich solution for certain periods, during which the intracellular Na+ concentration might be increased. Ad-hyperpolarization was depressed by lowering the temperature and by the action of ouabain, and the amplitude of Ad-hyperpolarization was markedly increased in the presence of TEA. The ionic mechanism underlying the generation of Ad-hyperpolarization was discussed on the basis of these present experimental results, and it was suggested that Ad-hyperpolarization might be generated by an electrogenic sodium pump.", "contents": "The electrogenesis of adrenaline-hyperpolarization of sympathetic ganglion cells in bullfrogs. Bullfrog sympathetic ganglion cells produced hyperpolarizing (Ad-hyperpolarization) and depolarizing (Ad-depolarization) responses when adrenaline (Ad) was directly applied to ganglia. The nature of Ad-hyperpolarization recorded by the sucrose-gap method was analysed in the present experiment, in order to clarify its electrogenesis. The amplitude of Ad-hyperpolarization was increased or decreased while ganglion cell membranes were hyperpolarized or depolarized, respectively, by applying a moderate conditioning current to the ganglia. The Ad-hyperpolarization was depressed in K+-rich solutions as well as in K+-deficient solutions. It was not significantly altered by replacing the extracellular total Cl ions by equimolar glutamate or thiosulfate ions. Ad-hyperpolarization was depressed and finally abolished in the Na+-free Tris solution, and was reversibly eliminated in the solution where Na ions were totally replaced by equimolar Li ions. It was enhanced when a preparation was previously perfused in the K+-free, Na+-rich solution for certain periods, during which the intracellular Na+ concentration might be increased. Ad-hyperpolarization was depressed by lowering the temperature and by the action of ouabain, and the amplitude of Ad-hyperpolarization was markedly increased in the presence of TEA. The ionic mechanism underlying the generation of Ad-hyperpolarization was discussed on the basis of these present experimental results, and it was suggested that Ad-hyperpolarization might be generated by an electrogenic sodium pump."}
{"id": "PMID:8662", "title": "Simplified operative technique for the long-segment atypical coarctation of the aorta.", "content": "Simplified operative technique for the long-segment atypical coarctation of the aorta was described. The main objective of this technique is to gain quick access to both thoracic and abdominal aorta with minimal blood loss, and preservation of diaphragmatic function. This procedure consists of standard thoracotomy and pararectal incision with an entry into the retroperitoneal space. Long prosthetic graft was anastomosed in an end-to-side fashion to bypass the coarctated aorta. The graft is placed through peripheral circumference of the left hemidiaphragm, where phrenic nerve injury is not likely to occur. This technique was successfully applied to two cases of long-segment atypical coarctation of the aorta due to Takayasu's aortitis. Retroperitoneal placement of the graft prevents fatal hemorrhage due to direct contact with the graft. Contamination with transintestinal exudate can also be avoided. Results of the ten-year follow-up of the similar procedure in the literature is encouraging.", "contents": "Simplified operative technique for the long-segment atypical coarctation of the aorta. Simplified operative technique for the long-segment atypical coarctation of the aorta was described. The main objective of this technique is to gain quick access to both thoracic and abdominal aorta with minimal blood loss, and preservation of diaphragmatic function. This procedure consists of standard thoracotomy and pararectal incision with an entry into the retroperitoneal space. Long prosthetic graft was anastomosed in an end-to-side fashion to bypass the coarctated aorta. The graft is placed through peripheral circumference of the left hemidiaphragm, where phrenic nerve injury is not likely to occur. This technique was successfully applied to two cases of long-segment atypical coarctation of the aorta due to Takayasu's aortitis. Retroperitoneal placement of the graft prevents fatal hemorrhage due to direct contact with the graft. Contamination with transintestinal exudate can also be avoided. Results of the ten-year follow-up of the similar procedure in the literature is encouraging."}
{"id": "PMID:8663", "title": "[Interrelations between blood pressure, blood volume, plasma renin and urinary catecholamines during beta-blockade in essential hypertension (author's transl)].", "content": "Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels.", "contents": "[Interrelations between blood pressure, blood volume, plasma renin and urinary catecholamines during beta-blockade in essential hypertension (author's transl)]. Studies in 55 patients with benign essential hypertension showed that the beta-blockers bufuralol (22 patients) and propranolol (33 patients) at a dose ratio of 1:4, possess comparable antihypertensive efficacy despite different properties regarding intrinsic sympathomimetic activity. Beta-blocker-monotherapy normalized blood pressure ( less than 140/90 mm Hg) in one fourth of the patients. Body weight and plasma and blood volumes remained unchanged during beta-blockade of four to six weeks duration, the mean plasma potassium was slightly increased. The inhibition of plasma renin activity (PRA) was more pronounced with propranolol (-69%) than with bufuralol (-47%). Wirth both beta-blockers decreases in blood pressure correlated inversely with pre-treatment PRA (p less than 0.05). Propranolol-induced changes in blood pressure correlated also with associated changes in PRA (p less than 0.005); in contrast, no such relationship was observed with bufuralol. The blood pressure effects of bufuralol, however, correlated significantly with changes in urinary noradrenaline excretion (r=0.41; p less than 0.05). Patient sub-groups with low, normal or high pre-treatment PRA in the average showed a comparable pattern of pre-treatment noradrenaline excretion and patients with normal renin levels exreted more adrenaline than those with low renin levels (p less than 0.001). These data are consistent with the concept that in untreated essential hypertension PRA may be an index of adrenergic activiity, the latter representing an important determinant of blood pressure response to beta-blockade. The blood pressure lowering effects of bufuralol in benign essential hypertension seem to be independent of renin and may be related, at least partly, to diminished free peripheral noradrenaline levels."}
{"id": "PMID:8664", "title": "[Specific and non-specific effects of beta-adreno-receptor blocking drugs in man (author's transl)].", "content": "The effect of tyramine infusion or exercise on catecholamine concentration and dopamine-beta-hydroxylase activity in plasma of normal volunteers has been studied. Whereas the increase in plasma catecholamine concentrations by tyramine infusion was not changed 90 min after oral application of a single dose of beta-adrenoceptor blocking drugs (penbutolol, practolol, I.C.I. 66082), the increase in blood pressure was diminished. However, the increase in plasma catecholamine, concentration, i.e. the adrenergic response to exercise was significantly enhanced during beta-adrenoceptor blockade. On the other hand, dopamine-beta-hydroxylase activity was not further increased during beta-adrenoceptor blockade. - The non-specific membrane activity of the beta-adrenoceptor blocking drugs wass assessed by the degree of inhibition of serotonin uptake by human platelets in vitro. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol less than penbutolol less than practolol less than I.C.I. 66082. The inhibitory activity of these drugs in vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration. Due to the high dose only propranolol showed a marked membrane activity.", "contents": "[Specific and non-specific effects of beta-adreno-receptor blocking drugs in man (author's transl)]. The effect of tyramine infusion or exercise on catecholamine concentration and dopamine-beta-hydroxylase activity in plasma of normal volunteers has been studied. Whereas the increase in plasma catecholamine concentrations by tyramine infusion was not changed 90 min after oral application of a single dose of beta-adrenoceptor blocking drugs (penbutolol, practolol, I.C.I. 66082), the increase in blood pressure was diminished. However, the increase in plasma catecholamine, concentration, i.e. the adrenergic response to exercise was significantly enhanced during beta-adrenoceptor blockade. On the other hand, dopamine-beta-hydroxylase activity was not further increased during beta-adrenoceptor blockade. - The non-specific membrane activity of the beta-adrenoceptor blocking drugs wass assessed by the degree of inhibition of serotonin uptake by human platelets in vitro. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol less than penbutolol less than practolol less than I.C.I. 66082. The inhibitory activity of these drugs in vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration. Due to the high dose only propranolol showed a marked membrane activity."}
{"id": "PMID:8669", "title": "The absorption of warfarin from the rat stomach in situ.", "content": "The absorption of warfarin from rat stomach was studied in situ by measuring the warfarin concentration in the gastric fluid, plasma, and the gastric wall concurrently. The warfarin concentrations in gastric fluid with initially acidic pH (pH 3 and pH 5) declined more rapidly than in initially neutral (pH 7) or basic (pH 8) fluid. However, the concurrent measurement of warfarin concentrations in plasma revealed that the absorption from initially neutral or basic fluids was faster in comparison with that measured from initially acidic milieu. This discrepancy resulted from a substantial accumulation of warfarin in the gastric wall mainly on mucosa due to the precipitation of the drug in acidic environment.", "contents": "The absorption of warfarin from the rat stomach in situ. The absorption of warfarin from rat stomach was studied in situ by measuring the warfarin concentration in the gastric fluid, plasma, and the gastric wall concurrently. The warfarin concentrations in gastric fluid with initially acidic pH (pH 3 and pH 5) declined more rapidly than in initially neutral (pH 7) or basic (pH 8) fluid. However, the concurrent measurement of warfarin concentrations in plasma revealed that the absorption from initially neutral or basic fluids was faster in comparison with that measured from initially acidic milieu. This discrepancy resulted from a substantial accumulation of warfarin in the gastric wall mainly on mucosa due to the precipitation of the drug in acidic environment."}
{"id": "PMID:8670", "title": "Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment.", "content": "6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development.", "contents": "Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment. 6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development."}
{"id": "PMID:8671", "title": "[Stellate ganglion blocks and vasodilator drugs in the treatment of perceptive deafness (author's transl)].", "content": "The results in the treatment of the idiopathetic perceptive deafness by means of stellate ganglion blocks and vasodilator drugs have been recorded. From 89 treated ears, 54% showed an improvement (some of them to a considerable degree). However, in 46% of the cases no significant improvement was effected.", "contents": "[Stellate ganglion blocks and vasodilator drugs in the treatment of perceptive deafness (author's transl)]. The results in the treatment of the idiopathetic perceptive deafness by means of stellate ganglion blocks and vasodilator drugs have been recorded. From 89 treated ears, 54% showed an improvement (some of them to a considerable degree). However, in 46% of the cases no significant improvement was effected."}
{"id": "PMID:8697", "title": "Chlorate toxicity in Aspergillus nidulans. Studies of mutants altered in nitrate assimilation.", "content": "It had previously been held that chlorate is not itself toxic, but is rendered toxic as a result of nitrate reductase-catalysed conversion to chlorite. This however cannot be the explanation of chlorate toxicity in Aspergillus nidulans, even though nitrate reductase is known to have chlorate reductase activity. Among other evidence against the classical theory for the mechanism of chlorate toxicity, is the finding that not all mutants lacking nitrate reductase are clorate resistant. Both chlorate-sensitive and resistant mutants lacking nitrate reductase, also lack chlorate reductase. Data is presented which implicates not only nitrate reductase but also the product of the nirA gene, a positive regulator gene for nitrate assimilation, in the mediation of chlorate toxicity. Alternative mechanisms for chlorate toxicity are considered. It is unlikely that chlorate toxicity results from the involvement of nitrate reductase and the nirA gene product in the regulation either of nitrite reductase, or of the pentose phosphate pathway. Although low pH has an effect similar to chlorate, chorate is not likely to be toxic because it lowers the pH; low pH and chlorate may instead have similar effects. A possible explanation for chlorate toxicity is that it mimics nitrate in mediating, via nitrate reductase and the nirA gene product, a shut-down of nitrogen catabolism. As chlorate cannot act as a nitrogen source, nitrogen starvation ensues.", "contents": "Chlorate toxicity in Aspergillus nidulans. Studies of mutants altered in nitrate assimilation. It had previously been held that chlorate is not itself toxic, but is rendered toxic as a result of nitrate reductase-catalysed conversion to chlorite. This however cannot be the explanation of chlorate toxicity in Aspergillus nidulans, even though nitrate reductase is known to have chlorate reductase activity. Among other evidence against the classical theory for the mechanism of chlorate toxicity, is the finding that not all mutants lacking nitrate reductase are clorate resistant. Both chlorate-sensitive and resistant mutants lacking nitrate reductase, also lack chlorate reductase. Data is presented which implicates not only nitrate reductase but also the product of the nirA gene, a positive regulator gene for nitrate assimilation, in the mediation of chlorate toxicity. Alternative mechanisms for chlorate toxicity are considered. It is unlikely that chlorate toxicity results from the involvement of nitrate reductase and the nirA gene product in the regulation either of nitrite reductase, or of the pentose phosphate pathway. Although low pH has an effect similar to chlorate, chorate is not likely to be toxic because it lowers the pH; low pH and chlorate may instead have similar effects. A possible explanation for chlorate toxicity is that it mimics nitrate in mediating, via nitrate reductase and the nirA gene product, a shut-down of nitrogen catabolism. As chlorate cannot act as a nitrogen source, nitrogen starvation ensues."}
{"id": "PMID:8702", "title": "Some properties of the adenosine triphosphatase systems of two yeast species, Saccharomyces cerevisiae and Rhodotorula glutinis.", "content": "1. Total ATPase levels were determined in homogenate fractions of baker's yeast, Saccharomyces cerevisiae K and Rhodotorula glutinis. The maximum ATPase activities in 8000 X g supernatant of the three yeast strains were 6.0, 1.9, and 2.2 mmol Pih-1 (gDS)-1, respectively; the activities in the sediment were somewhat higher. Exponential cells of S. cerevisiae K and R. glutinis exhibited higher ATPase levels than did the stationary cells. 2. The total ATPase activity in both yeast species showed a maximum at ph 6.8 a minimum at pH 7.2, and another broader masimum around pH 8.0. 3. No significant NaK-ATPase activity was detected in baker's yeast, in either the exponential or the stationary cells of R. glutinis, and in exponential S. cerevisiae K cells in the pH range of 6.0-9.3. 4. Stationary cells of S. cerevisiae K exhibited, at pH 7.0-8.5, A Na,K-ATPase activity attaining 9% of total ATPase level. 5.3 X 10(-3) M phenylmethyl sulphonyl fluoride had no effect on the total ATPase level in S. cerevisiae and inhibited the activity in R. glutinis by 25%; it did not bring forth any Na,K-ATPase activity apart from that found in its absence. 6. 1.5 M urea lowered the ATPase activity in R. glutinis by 68% but had no effect on S. cerevisiae cells. 10(-5) M dicyclohexylcarbodiimide suppressed the ATPase activity in S. cerevisiae and R. glutinis by 74 and 79%, respectively. Neither agent revealed and additional Na,K-ATPase activity. 7. The comparison of Na,K-ATPase activities with data on K+ fluxes across the yeast plasma membrane suggested that even with the lower flux values the Na,K-ATPase, even if present, would account for a mere 40% of transported ions. The results imply that the active ion transport in yeasts is energized by mechanisms other than the Na,K-ATPase.", "contents": "Some properties of the adenosine triphosphatase systems of two yeast species, Saccharomyces cerevisiae and Rhodotorula glutinis. 1. Total ATPase levels were determined in homogenate fractions of baker's yeast, Saccharomyces cerevisiae K and Rhodotorula glutinis. The maximum ATPase activities in 8000 X g supernatant of the three yeast strains were 6.0, 1.9, and 2.2 mmol Pih-1 (gDS)-1, respectively; the activities in the sediment were somewhat higher. Exponential cells of S. cerevisiae K and R. glutinis exhibited higher ATPase levels than did the stationary cells. 2. The total ATPase activity in both yeast species showed a maximum at ph 6.8 a minimum at pH 7.2, and another broader masimum around pH 8.0. 3. No significant NaK-ATPase activity was detected in baker's yeast, in either the exponential or the stationary cells of R. glutinis, and in exponential S. cerevisiae K cells in the pH range of 6.0-9.3. 4. Stationary cells of S. cerevisiae K exhibited, at pH 7.0-8.5, A Na,K-ATPase activity attaining 9% of total ATPase level. 5.3 X 10(-3) M phenylmethyl sulphonyl fluoride had no effect on the total ATPase level in S. cerevisiae and inhibited the activity in R. glutinis by 25%; it did not bring forth any Na,K-ATPase activity apart from that found in its absence. 6. 1.5 M urea lowered the ATPase activity in R. glutinis by 68% but had no effect on S. cerevisiae cells. 10(-5) M dicyclohexylcarbodiimide suppressed the ATPase activity in S. cerevisiae and R. glutinis by 74 and 79%, respectively. Neither agent revealed and additional Na,K-ATPase activity. 7. The comparison of Na,K-ATPase activities with data on K+ fluxes across the yeast plasma membrane suggested that even with the lower flux values the Na,K-ATPase, even if present, would account for a mere 40% of transported ions. The results imply that the active ion transport in yeasts is energized by mechanisms other than the Na,K-ATPase."}
{"id": "PMID:8703", "title": "Oxidation of S-e-carboxymethyl-selenocysteine by L-aminoacid oxidase and by D-aspartate oxidase.", "content": "Se-Carboxymethyl-DL-selnocysteine (CMSeC) has been prepared in a pure crystalline form from selenocysteine and monochloracetic acid. It has been shown that CMSeC is a substrate for the L-aminoacid oxidase form snake venom and for the D-aspartate oxidase from beef kidney. Oxygen consumption and ammonia production indicate that only the L or the D form of CMSeC ar acted upon respectively by one or the other of the above enzymes. No noticeable differences were shown in the oxidation rate of CMSeC and S-carboxymethylcysteine, an indication that the substitution of a selenium for a sulfur atom in the molecule does not greatly affect the substrate specificity of the two enzymes. Data have been obtained suggesting that the product of the oxidative deamination of CMSeC Is Se-carboxymethyl-selenopyruvic acid.", "contents": "Oxidation of S-e-carboxymethyl-selenocysteine by L-aminoacid oxidase and by D-aspartate oxidase. Se-Carboxymethyl-DL-selnocysteine (CMSeC) has been prepared in a pure crystalline form from selenocysteine and monochloracetic acid. It has been shown that CMSeC is a substrate for the L-aminoacid oxidase form snake venom and for the D-aspartate oxidase from beef kidney. Oxygen consumption and ammonia production indicate that only the L or the D form of CMSeC ar acted upon respectively by one or the other of the above enzymes. No noticeable differences were shown in the oxidation rate of CMSeC and S-carboxymethylcysteine, an indication that the substitution of a selenium for a sulfur atom in the molecule does not greatly affect the substrate specificity of the two enzymes. Data have been obtained suggesting that the product of the oxidative deamination of CMSeC Is Se-carboxymethyl-selenopyruvic acid."}
{"id": "PMID:8704", "title": "Studies on selenium-related compounds. V. Cytogenetic effect and reactivity with DNA.", "content": "Five selenium compounds, Na2Se04, H2Se04, Na2Se03, H2Se03 and Se02, were tested for their capacity to induce chromosome aberrations in cultured human leukocytes and for their reactivity with DNA by a rec-assay system and inactivation of transforming activity in Bacillus subtilis. Chromosome-breaking activity was significantly higher for the compounds with four-valent than with six-valent selenium, the efficiency being in the decreasing order H2S03 greater than Na2Se03 greater than Se02 greater than H2Se04 greater than Na2Se04. Rec assay using B. subtilis with different recombination capacities suggested that damage to DNA was produced by selenites but not by selenates. The reactivity of selenites with DNA was also indicated by a significant loss of transformation of the tryptophan marker of B. subtilis DNA treated with H2Se03 and Se02.", "contents": "Studies on selenium-related compounds. V. Cytogenetic effect and reactivity with DNA. Five selenium compounds, Na2Se04, H2Se04, Na2Se03, H2Se03 and Se02, were tested for their capacity to induce chromosome aberrations in cultured human leukocytes and for their reactivity with DNA by a rec-assay system and inactivation of transforming activity in Bacillus subtilis. Chromosome-breaking activity was significantly higher for the compounds with four-valent than with six-valent selenium, the efficiency being in the decreasing order H2S03 greater than Na2Se03 greater than Se02 greater than H2Se04 greater than Na2Se04. Rec assay using B. subtilis with different recombination capacities suggested that damage to DNA was produced by selenites but not by selenates. The reactivity of selenites with DNA was also indicated by a significant loss of transformation of the tryptophan marker of B. subtilis DNA treated with H2Se03 and Se02."}
{"id": "PMID:8706", "title": "New method for evaluation of freshness degree in fish and its products.", "content": "The method is based on the determination of the content of fish meat of soluble, non-heat-precipitable protein which is brought in relation to the total amount of sarcoplasmic protein. The method is also suited to evaluate the freshness of iced fish where other procedures sometimes fail, which is due to the interference of the melted ice.", "contents": "New method for evaluation of freshness degree in fish and its products. The method is based on the determination of the content of fish meat of soluble, non-heat-precipitable protein which is brought in relation to the total amount of sarcoplasmic protein. The method is also suited to evaluate the freshness of iced fish where other procedures sometimes fail, which is due to the interference of the melted ice."}
{"id": "PMID:8714", "title": "[Dry matter losses in mushroom (Lactarius rufus) by blanching].", "content": "According to recommended international standards edible fungi are blanched before salting and freezing. A study was conducted on the solution losses of Lactarius rufus due to blanching. Weight losses, changes of dry matter, raw fat, total nitrogen, amino nitrogen and ash contents as well as the pH value were determined when various methods of blanching were used. 3 min blanching at 95-100 degrees C was able to inactivate catalase and peroxydase while 6 min blanching was needed for inactivating polyphenoloxydase totally. After blanching there were 1/10 - 1/100 of spores left. During the 3 min blanching in water five times the quantity of mushrooms the losses of dry matter were about 10%; when doubling the quantity of blanching water the losses increased to 2-3 fold. The doubling of blanching time had no significant influence on the losses. The soluble dry matter content of blanched mushrooms was less than 50% of that of the fresh. Total nitrogen of fresh mushrooms was equal to that of the blanched but the amino nitrogen decreased to one tenth by blanching. The mineral element content of blanched mushrooms was about the half of that of the fresh. Blanching caused a slight decrease in the pH value. The necessity of the blanching of all edible fungi before freezing was discussed.", "contents": "[Dry matter losses in mushroom (Lactarius rufus) by blanching]. According to recommended international standards edible fungi are blanched before salting and freezing. A study was conducted on the solution losses of Lactarius rufus due to blanching. Weight losses, changes of dry matter, raw fat, total nitrogen, amino nitrogen and ash contents as well as the pH value were determined when various methods of blanching were used. 3 min blanching at 95-100 degrees C was able to inactivate catalase and peroxydase while 6 min blanching was needed for inactivating polyphenoloxydase totally. After blanching there were 1/10 - 1/100 of spores left. During the 3 min blanching in water five times the quantity of mushrooms the losses of dry matter were about 10%; when doubling the quantity of blanching water the losses increased to 2-3 fold. The doubling of blanching time had no significant influence on the losses. The soluble dry matter content of blanched mushrooms was less than 50% of that of the fresh. Total nitrogen of fresh mushrooms was equal to that of the blanched but the amino nitrogen decreased to one tenth by blanching. The mineral element content of blanched mushrooms was about the half of that of the fresh. Blanching caused a slight decrease in the pH value. The necessity of the blanching of all edible fungi before freezing was discussed."}
{"id": "PMID:8716", "title": "[Complex gels of proteins and acid polysaccharides].", "content": "The authors studied the thermomechanical properties of complex gels of gelatin and sodium alginate which had been produced on the basis of their insoluble (type I) and soluble (type II) complexes. Compared to gelatin gels of the same concentration, the complex gels I have higher melting points. The latter depend on the pH value at which the insoluble complexes of gelatin and sodium alginate were separated. Up to temperatures from 70 degrees--80 degrees C., no melting of the complex gels II was observed. The aging time and the composition of the soluble complexes of gelatin and sodium alginate exert no marked effects on the properties of the complex gels II. The soluble complexes of gelatin and sodium alginate can form gels in 7 M urea solutions.", "contents": "[Complex gels of proteins and acid polysaccharides]. The authors studied the thermomechanical properties of complex gels of gelatin and sodium alginate which had been produced on the basis of their insoluble (type I) and soluble (type II) complexes. Compared to gelatin gels of the same concentration, the complex gels I have higher melting points. The latter depend on the pH value at which the insoluble complexes of gelatin and sodium alginate were separated. Up to temperatures from 70 degrees--80 degrees C., no melting of the complex gels II was observed. The aging time and the composition of the soluble complexes of gelatin and sodium alginate exert no marked effects on the properties of the complex gels II. The soluble complexes of gelatin and sodium alginate can form gels in 7 M urea solutions."}
{"id": "PMID:8717", "title": "[Structure and properties of complex gels of gelatin and pectin].", "content": "The authors studied the effects of aging time and composition on the thermomechanical properties of complex gels of gelatin and pectin which had been produced on the basis of complexes obtained at pH values below the isoelectric point of gelatin. With aging for up to 7 days, the elasticity of the gels decreases and the melting points are raised by 2--4degreesC. An increase in the relative content of pectin in the complex leads to a considerable rise of the melting point of the complex gel. The increase in heat stability of these gels is explained by the development of an ion lattice, which is due to the interaction of the oppositely charged groups of the pectin and the gelatin. Furthermore, hydrophobic interactions between the non-polar groups of the components might be involved.", "contents": "[Structure and properties of complex gels of gelatin and pectin]. The authors studied the effects of aging time and composition on the thermomechanical properties of complex gels of gelatin and pectin which had been produced on the basis of complexes obtained at pH values below the isoelectric point of gelatin. With aging for up to 7 days, the elasticity of the gels decreases and the melting points are raised by 2--4degreesC. An increase in the relative content of pectin in the complex leads to a considerable rise of the melting point of the complex gel. The increase in heat stability of these gels is explained by the development of an ion lattice, which is due to the interaction of the oppositely charged groups of the pectin and the gelatin. Furthermore, hydrophobic interactions between the non-polar groups of the components might be involved."}
{"id": "PMID:8718", "title": "[Significance of starter cultures for raw sausage aging in view of food and nutrition hygiene].", "content": "The authors studied the effects of liquid starter cultures on the survival of pathogenic germs. It was found that the foreign bacteria tested differed in growth limitation which is obviously dependent on acidity and the amount of lactic acid produced by fermentation. Since the pathogenic bacteria differ in the ability to survive, it is imperative to observe strict hygienic measures in preparing starter cultures and to use absolutely sterile monocultures for raw sausage ageing.", "contents": "[Significance of starter cultures for raw sausage aging in view of food and nutrition hygiene]. The authors studied the effects of liquid starter cultures on the survival of pathogenic germs. It was found that the foreign bacteria tested differed in growth limitation which is obviously dependent on acidity and the amount of lactic acid produced by fermentation. Since the pathogenic bacteria differ in the ability to survive, it is imperative to observe strict hygienic measures in preparing starter cultures and to use absolutely sterile monocultures for raw sausage ageing."}
{"id": "PMID:8719", "title": "[Rheology and spinning of alkaline solution of field bean protein and casein].", "content": "From field bean protein and a mixture of field bean protein with casein to equal parts are prepared with sodium hydroxide high protein-containing alkaline solutions, which show pseudoplastic flow. The flow curves of the pseudoplastic field bean protein-casein (I:I)-solutions are described mathematically with the Ostwaldian power statement. In a suitable scope of spinning of this solutions are carried out complete factorial experiments, which guide to regression equations of lg k and n. g k depends on the concentration of protein; an effect of the sodium hydroxide concentration exists lonly about interactions. On the other hand the flow exponent n depends on the hydroxide concentration. The properties of the spun field bean protein/casein (I:I) fibres are described.", "contents": "[Rheology and spinning of alkaline solution of field bean protein and casein]. From field bean protein and a mixture of field bean protein with casein to equal parts are prepared with sodium hydroxide high protein-containing alkaline solutions, which show pseudoplastic flow. The flow curves of the pseudoplastic field bean protein-casein (I:I)-solutions are described mathematically with the Ostwaldian power statement. In a suitable scope of spinning of this solutions are carried out complete factorial experiments, which guide to regression equations of lg k and n. g k depends on the concentration of protein; an effect of the sodium hydroxide concentration exists lonly about interactions. On the other hand the flow exponent n depends on the hydroxide concentration. The properties of the spun field bean protein/casein (I:I) fibres are described."}
{"id": "PMID:8722", "title": "[Effects of technological additives and heating range on some chemical and physical changes in canned meat. 2. Changes in redox potentials and selected quality characteristics].", "content": "The influence of technological additives and the range of heating on the redox potential, as well as on some quality features of canned meat was examined. The experiments showed, that the time of storage and the degree of heating of model preserves of meat influence on the redox potential. The technological additions as polyphosphates, ascorbic acid, gelatine and mixtures of these substances influence less on the redox potential. The analysis of each experimental factor showed, that on the secretion of meat juice occurring during can pasteurization or sterilization influence all experimental factors, as the kind of heating, the time of storage as well as the kind and the quantity of technological additives. The highest secretion of meat juice was found in cans with addition of ascorbic acid. Cans with addition of gelatine had the smallest content of jelly and consequently the lowest secretion of meat juice. It was also found a certain relation between the level of redox potential and the tested quality features of the model meat preserves.", "contents": "[Effects of technological additives and heating range on some chemical and physical changes in canned meat. 2. Changes in redox potentials and selected quality characteristics]. The influence of technological additives and the range of heating on the redox potential, as well as on some quality features of canned meat was examined. The experiments showed, that the time of storage and the degree of heating of model preserves of meat influence on the redox potential. The technological additions as polyphosphates, ascorbic acid, gelatine and mixtures of these substances influence less on the redox potential. The analysis of each experimental factor showed, that on the secretion of meat juice occurring during can pasteurization or sterilization influence all experimental factors, as the kind of heating, the time of storage as well as the kind and the quantity of technological additives. The highest secretion of meat juice was found in cans with addition of ascorbic acid. Cans with addition of gelatine had the smallest content of jelly and consequently the lowest secretion of meat juice. It was also found a certain relation between the level of redox potential and the tested quality features of the model meat preserves."}
{"id": "PMID:8723", "title": "[Characterization and spinning of alkaline solutions of wheat protein and casein].", "content": "The viscosity behaviour of alkaline solutions of mixtures from different wheat glutens with casein in dependence on the concentration of the whole protein, wheat protein, sodium hydroxide, sodium chloride and on the temperature, time and the effect of treatment of wet wheat gluten with sodium chloride or sodium hydroxide on the properties of the spun wheat protein/casein fibers are described. Based on this model experiments the rheological behaviour of alkaline solutions of wheat protein/casein (I:2) and proceed from the parameters of the spinning process the properties of the corresponding spun fibers are represented.", "contents": "[Characterization and spinning of alkaline solutions of wheat protein and casein]. The viscosity behaviour of alkaline solutions of mixtures from different wheat glutens with casein in dependence on the concentration of the whole protein, wheat protein, sodium hydroxide, sodium chloride and on the temperature, time and the effect of treatment of wet wheat gluten with sodium chloride or sodium hydroxide on the properties of the spun wheat protein/casein fibers are described. Based on this model experiments the rheological behaviour of alkaline solutions of wheat protein/casein (I:2) and proceed from the parameters of the spinning process the properties of the corresponding spun fibers are represented."}
{"id": "PMID:8729", "title": "Intracellular pH and activation of sea urchin eggs after fertilisation.", "content": "The intracellular pH of the sea urchin embryo increases 0.3 pH units between 1 and 4 min after fertilisation. The increase in pH is required for initiating development. The increase results from an exchange of extracellular Na+ for intracellular H+.", "contents": "Intracellular pH and activation of sea urchin eggs after fertilisation. The intracellular pH of the sea urchin embryo increases 0.3 pH units between 1 and 4 min after fertilisation. The increase in pH is required for initiating development. The increase results from an exchange of extracellular Na+ for intracellular H+."}
{"id": "PMID:8732", "title": "Formation of stable crystalline enzyme-substrate intermediates at sub-zero temperatures.", "content": "Sub-zero temperatures can be used to trap intermediates in enzyme-catalysed reactions using suitable cryosolvents. The feasibility of obtaining such intermediates in the crystalline state for X-ray diffraction studies has been demonstrated with several proteases, using specific substrates and optimal pH.", "contents": "Formation of stable crystalline enzyme-substrate intermediates at sub-zero temperatures. Sub-zero temperatures can be used to trap intermediates in enzyme-catalysed reactions using suitable cryosolvents. The feasibility of obtaining such intermediates in the crystalline state for X-ray diffraction studies has been demonstrated with several proteases, using specific substrates and optimal pH."}
{"id": "PMID:8734", "title": "Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo.", "content": "The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems.", "contents": "Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo. The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems."}
{"id": "PMID:8735", "title": "The cardiovascular effects of intraventricularly administered histamine in the anaesthetised rat.", "content": "In urethane-anaestetised rats intraventricular (i.c.v.) injections of histamine (0.1-10.0mug) elicited dose-related rises in both the resting blood pressure and heart rate. These cardiovascular effects of histamine were antagonised in a dose-dependent manner by i.c.v. pretreatments with the histamine H1-receptor antagonists mepyramine (10, 50 and 100 mug) and diphenylpyraline (100 and 200mug). Pretreatment with the histamine H2-receptor antagonist metiamide (100 and 200 mug i.c.v.) failed to modify either of the responses. A dose-related antagonism of the hypertensive response to histamine i.c.v. was elicited by phentolamine (100 and 200 mug i.c.v.) but the positive chronotropic effect was not modified by this pretreatment. The cardiovascular responses to histamine i.c.v. were abolished by mecamylamine (5.0 mg/kg i.v.) and greatly reduced by 6-hydroxydopamine (3 X 250 mug i.c.v.), but only the tachycardia was significantly modified by atropine (100 mug i.c.v.) and propranolol (1 mg/kg i.v.). Propranolol (100 mug i.c.v.), bilateral vagotomy, or acute bilateral adrenal demedullation failed to modify the cardiovascular responses to histamine i.c.v. The results suggest that histamine is able to modify the resting blood pressure and heart rate by independent central modes of action, which involve central adrenergic and cholinergic mechanisms.", "contents": "The cardiovascular effects of intraventricularly administered histamine in the anaesthetised rat. In urethane-anaestetised rats intraventricular (i.c.v.) injections of histamine (0.1-10.0mug) elicited dose-related rises in both the resting blood pressure and heart rate. These cardiovascular effects of histamine were antagonised in a dose-dependent manner by i.c.v. pretreatments with the histamine H1-receptor antagonists mepyramine (10, 50 and 100 mug) and diphenylpyraline (100 and 200mug). Pretreatment with the histamine H2-receptor antagonist metiamide (100 and 200 mug i.c.v.) failed to modify either of the responses. A dose-related antagonism of the hypertensive response to histamine i.c.v. was elicited by phentolamine (100 and 200 mug i.c.v.) but the positive chronotropic effect was not modified by this pretreatment. The cardiovascular responses to histamine i.c.v. were abolished by mecamylamine (5.0 mg/kg i.v.) and greatly reduced by 6-hydroxydopamine (3 X 250 mug i.c.v.), but only the tachycardia was significantly modified by atropine (100 mug i.c.v.) and propranolol (1 mg/kg i.v.). Propranolol (100 mug i.c.v.), bilateral vagotomy, or acute bilateral adrenal demedullation failed to modify the cardiovascular responses to histamine i.c.v. The results suggest that histamine is able to modify the resting blood pressure and heart rate by independent central modes of action, which involve central adrenergic and cholinergic mechanisms."}
{"id": "PMID:8736", "title": "The haemolytic effect of phallolysin.", "content": "Phallolysin from the toadstool, Amanita phalloides, is a basic protein that causes direct haemolysis of red cells. The dose-response curve is steep; the pH optimum is in the weakly acid range. The rate of haemolysis increases with the concentration of the lysin, the optimal temperature is 20 degrees C. The percentage haemolysis-time curves are S-shaped. Haemolysis is of the non-osmotic type. Ca2+ is not required but inhibits haemolysis in a concentration-dependent fashion, as do Mg2+ and Zn2+. The red cell sensitivity of various animal species decreases in the following sequence:mouse greater than rabbit = guniea pig greater than rat greater than man greater than dog approximately or equal to pig greater than sheep = cattle. Red cells of cattle and sheep are largely resistant. Phallolysin is virtually not consumed on haemalysis: the amount of haemoglobin released increases with the number of red cells applied; on repeated addition of fresh red cells the haemolysate retains its full activity. Phallolysin is not inhibited by serum, albumin, cholesterol, lecithin, cephalin or sphingomyelin; inhibition by red cell ghosts of phallolysin haemolysis is considerably less than that of digitonin haemolysis. At sublytic concentrations phallolysin, unlike benzalkonium chloride, liberates practically no membrane lipids from human red cells. Surface activity of phallolysin does not exceed that of bovine serum albumin.-A saponin-like interaction with cholesterol as the basic mechanism of haemolysis can be disregarded. There is also no evidence suggesting a detergent-like effect.", "contents": "The haemolytic effect of phallolysin. Phallolysin from the toadstool, Amanita phalloides, is a basic protein that causes direct haemolysis of red cells. The dose-response curve is steep; the pH optimum is in the weakly acid range. The rate of haemolysis increases with the concentration of the lysin, the optimal temperature is 20 degrees C. The percentage haemolysis-time curves are S-shaped. Haemolysis is of the non-osmotic type. Ca2+ is not required but inhibits haemolysis in a concentration-dependent fashion, as do Mg2+ and Zn2+. The red cell sensitivity of various animal species decreases in the following sequence:mouse greater than rabbit = guniea pig greater than rat greater than man greater than dog approximately or equal to pig greater than sheep = cattle. Red cells of cattle and sheep are largely resistant. Phallolysin is virtually not consumed on haemalysis: the amount of haemoglobin released increases with the number of red cells applied; on repeated addition of fresh red cells the haemolysate retains its full activity. Phallolysin is not inhibited by serum, albumin, cholesterol, lecithin, cephalin or sphingomyelin; inhibition by red cell ghosts of phallolysin haemolysis is considerably less than that of digitonin haemolysis. At sublytic concentrations phallolysin, unlike benzalkonium chloride, liberates practically no membrane lipids from human red cells. Surface activity of phallolysin does not exceed that of bovine serum albumin.-A saponin-like interaction with cholesterol as the basic mechanism of haemolysis can be disregarded. There is also no evidence suggesting a detergent-like effect."}
{"id": "PMID:8737", "title": "Desensitization of kitten atria to chronotropic, inotropic and adenylyl cyclase stimulating effects of (-)isoprenaline.", "content": "Desensitization of kitten atria with 30muM (-)isoprenaline resulted in a 6-fold and 15-fold increase in the EC50's of (-)isoprenaline for its positive chronotropic effects (sinus pacemakers) and positive inotropic effects (left atria), respectively, but only in a 2-fold increase of the EC50 of (-)isoprenaline for adenylyl cyclase stimulation in membrane particles from atria. However, maximum cyclase stimulation by (-)isoprenaline was decreased to 1/2 in membranes from (-)isoprenaline-treated atria, whereas maximum increases in rate of sinus pacemakers and force of left atria were unchanged and reduced by 15%, respectively. The high affinity beta-adrenoceptor blocker (-)bupranolol antagonized the adenylyl cyclase stimulation by (-)isoprenaline to similar extent in membranes from (-)isoprenaline and untreated atria, suggesting that the apparent affinity of beta-adrenoceptors for  ligands is unchanged by desensitization. The evidence is compatible with the concept that desensitization is associated with decreased availability of receptors and with the view that near maximal positive chronotropic effects of catecholamines may be caused by only threshold increases in membrane adenylyl cyclase activity.", "contents": "Desensitization of kitten atria to chronotropic, inotropic and adenylyl cyclase stimulating effects of (-)isoprenaline. Desensitization of kitten atria with 30muM (-)isoprenaline resulted in a 6-fold and 15-fold increase in the EC50's of (-)isoprenaline for its positive chronotropic effects (sinus pacemakers) and positive inotropic effects (left atria), respectively, but only in a 2-fold increase of the EC50 of (-)isoprenaline for adenylyl cyclase stimulation in membrane particles from atria. However, maximum cyclase stimulation by (-)isoprenaline was decreased to 1/2 in membranes from (-)isoprenaline-treated atria, whereas maximum increases in rate of sinus pacemakers and force of left atria were unchanged and reduced by 15%, respectively. The high affinity beta-adrenoceptor blocker (-)bupranolol antagonized the adenylyl cyclase stimulation by (-)isoprenaline to similar extent in membranes from (-)isoprenaline and untreated atria, suggesting that the apparent affinity of beta-adrenoceptors for  ligands is unchanged by desensitization. The evidence is compatible with the concept that desensitization is associated with decreased availability of receptors and with the view that near maximal positive chronotropic effects of catecholamines may be caused by only threshold increases in membrane adenylyl cyclase activity."}
{"id": "PMID:8738", "title": "The comparison of aminotransferase activities in normal and Guerin epithelioma bearing rats.", "content": "The activities of 13 aminotransferawes in Guerin epithelioma and in the liver of normal and tumor bearing rats were investigated. Alanine and aspartate aminotransferases show the highest activity in all investigated tissues. In the liver of normal rats high arginine, tyrosine and phenylalanine aminotransferase activities were found. In tumor tissue high level of branched chain amino acid (leucine, valine and isoleucine) aminotransferases were observed. Increase in aminotransferase activities in the liver of tumor bearing rats was found. In order to elucidate the mechanism of this increase an inductive effect of hydrocortisone and protein free extract of tumor tissue on liver aminotransferases has been investigated. The tumor extract did not exert an inductive action. An inductive effect of hydrocortisone was not identical with the change in aminotransferase activities observed in the liver of tumor bearing rats.", "contents": "The comparison of aminotransferase activities in normal and Guerin epithelioma bearing rats. The activities of 13 aminotransferawes in Guerin epithelioma and in the liver of normal and tumor bearing rats were investigated. Alanine and aspartate aminotransferases show the highest activity in all investigated tissues. In the liver of normal rats high arginine, tyrosine and phenylalanine aminotransferase activities were found. In tumor tissue high level of branched chain amino acid (leucine, valine and isoleucine) aminotransferases were observed. Increase in aminotransferase activities in the liver of tumor bearing rats was found. In order to elucidate the mechanism of this increase an inductive effect of hydrocortisone and protein free extract of tumor tissue on liver aminotransferases has been investigated. The tumor extract did not exert an inductive action. An inductive effect of hydrocortisone was not identical with the change in aminotransferase activities observed in the liver of tumor bearing rats."}
{"id": "PMID:8739", "title": "[Etiology of cerebral vasospasm].", "content": "Basing on prior investigations, the site of action of an alpha-adrenergic substance liberated by platelets, which elicit cerebral vasospasm, was precisely located experimentally in white mice. It could be shown, that this substance incites the alpha-receptors of the smooth muscle cells, because the depletion of catecholamines in the postsynaptic nervous fibres by Tyramine does not abolish the capability for cerebral vasospasm. Furthermore could be shown, that stimulation of beta-receptors by Isoproterenol can inhibit the vasospasm completely.", "contents": "[Etiology of cerebral vasospasm]. Basing on prior investigations, the site of action of an alpha-adrenergic substance liberated by platelets, which elicit cerebral vasospasm, was precisely located experimentally in white mice. It could be shown, that this substance incites the alpha-receptors of the smooth muscle cells, because the depletion of catecholamines in the postsynaptic nervous fibres by Tyramine does not abolish the capability for cerebral vasospasm. Furthermore could be shown, that stimulation of beta-receptors by Isoproterenol can inhibit the vasospasm completely."}
{"id": "PMID:8741", "title": "Involvement of catecholaminergic and cholinergic mechanisms in the pulsatile release of LH in the long-term ovariectomized rat.", "content": "In the long-term ovariectomized rat the secretion of LH has a pulsatile character. In such rats no difference was observed between morning and afternoon LH secretion. The administration of phenoxybenzamine, an chi-adrenergic blocker, resulted in depressed plasma LH levels. chi-Methyl-tyrosine (chi-MT), an inhibitor of tyrosine hydroxylase had no effect on plasma LH levels, whereas bis(4methyl-1-homopiperazinil-thiocarbonil) disulphide (FLA 63), an inhibitor of dopaminic-beta-hydroxylase, induced decreased plasma LH levels and disappearance of the pulsations. The same effect was observed after the administration of apomorphine, a dopaminic receptor stimulating drug, whereas the administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966), which blocks dopamine release, significantly raised plasma LH levels. Scopolamine, a cholinergic muscarinic receptor blocking drug, had no effect on plasma LH levels, whereas mecamylamine, a cholinergic nicotine receptor blocking agent, decreased them. These results are consistent with the hypothesis that the pulsatile release of LH in the long-term ovariectomized rat is caused by the stimulating activity of adrenergic and cholinergic, probably nicotinic, systems and the inhibitory activity of a dopaminergic system.", "contents": "Involvement of catecholaminergic and cholinergic mechanisms in the pulsatile release of LH in the long-term ovariectomized rat. In the long-term ovariectomized rat the secretion of LH has a pulsatile character. In such rats no difference was observed between morning and afternoon LH secretion. The administration of phenoxybenzamine, an chi-adrenergic blocker, resulted in depressed plasma LH levels. chi-Methyl-tyrosine (chi-MT), an inhibitor of tyrosine hydroxylase had no effect on plasma LH levels, whereas bis(4methyl-1-homopiperazinil-thiocarbonil) disulphide (FLA 63), an inhibitor of dopaminic-beta-hydroxylase, induced decreased plasma LH levels and disappearance of the pulsations. The same effect was observed after the administration of apomorphine, a dopaminic receptor stimulating drug, whereas the administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966), which blocks dopamine release, significantly raised plasma LH levels. Scopolamine, a cholinergic muscarinic receptor blocking drug, had no effect on plasma LH levels, whereas mecamylamine, a cholinergic nicotine receptor blocking agent, decreased them. These results are consistent with the hypothesis that the pulsatile release of LH in the long-term ovariectomized rat is caused by the stimulating activity of adrenergic and cholinergic, probably nicotinic, systems and the inhibitory activity of a dopaminergic system."}
{"id": "PMID:8742", "title": "Chronic treatment with reserpine and adrenocortical activation.", "content": "Daily i.p. injection of reserpine for 9 days strongly depletes hypothalamic norephinephrine (NE); after an initial activation, adrenocortical function returns to control values by the 5th day. Tyrosine hydroxylase (TH) activity in the brain stem of reserpine-treated rats exhibits a progressive increase. Alpha-methyl-para-tyrosine (chi-MpT) in rats chronically pretreated with reserpine provokes adrenocortical activation and a further decrease of hypothalamic NE. Exogenous ACTH in the same animals revealed an unimpaired adrenocortical reactivity after prolonged treatment with reserpine. These results seem to suggest that the disappearance of adrenocortical activation following long-term treatment with reserpine is due to the stimulated formation of a small functional pool of NE available for the tonic inhibition of CRF-ACTH secretion.", "contents": "Chronic treatment with reserpine and adrenocortical activation. Daily i.p. injection of reserpine for 9 days strongly depletes hypothalamic norephinephrine (NE); after an initial activation, adrenocortical function returns to control values by the 5th day. Tyrosine hydroxylase (TH) activity in the brain stem of reserpine-treated rats exhibits a progressive increase. Alpha-methyl-para-tyrosine (chi-MpT) in rats chronically pretreated with reserpine provokes adrenocortical activation and a further decrease of hypothalamic NE. Exogenous ACTH in the same animals revealed an unimpaired adrenocortical reactivity after prolonged treatment with reserpine. These results seem to suggest that the disappearance of adrenocortical activation following long-term treatment with reserpine is due to the stimulated formation of a small functional pool of NE available for the tonic inhibition of CRF-ACTH secretion."}
{"id": "PMID:8740", "title": "[Statistical analysis of cerebrospinal fluid acid-base equilibrium and cerebrospinal fluid lactate concentration in cases of brain tumors, cerebrocranial injuries and meningoencephalitis].", "content": "A statistical analysis of CSF lactate concentration and CSF pH and PCO2 was performed. The values were obtained from 211 samples taken from 76 neurosurgical patients. The values of pH and pCO2 were classified in three groups corresponding to the following three ranges of lactate concentration: below 15 mg%, 15-30 mg%, over 30 mg%. The mean values and standard deviations were calculated: suitable tests: F, t (Student), C (Cochran and Cox) were used. It was established, that statistically significant changes of CSF acid-base balance were present at lactate levels over 30 mg%. Next, the patients with lactate concentrations over 30 mg% were analysed. They were divided into three groups according to etiology: inflammatory changes, injuries, tumours. It was shown, that the CSF acid-base balance in patients with brain tumours is less disturbed then in patients with inflammatory changes or brain injury.", "contents": "[Statistical analysis of cerebrospinal fluid acid-base equilibrium and cerebrospinal fluid lactate concentration in cases of brain tumors, cerebrocranial injuries and meningoencephalitis]. A statistical analysis of CSF lactate concentration and CSF pH and PCO2 was performed. The values were obtained from 211 samples taken from 76 neurosurgical patients. The values of pH and pCO2 were classified in three groups corresponding to the following three ranges of lactate concentration: below 15 mg%, 15-30 mg%, over 30 mg%. The mean values and standard deviations were calculated: suitable tests: F, t (Student), C (Cochran and Cox) were used. It was established, that statistically significant changes of CSF acid-base balance were present at lactate levels over 30 mg%. Next, the patients with lactate concentrations over 30 mg% were analysed. They were divided into three groups according to etiology: inflammatory changes, injuries, tumours. It was shown, that the CSF acid-base balance in patients with brain tumours is less disturbed then in patients with inflammatory changes or brain injury."}
{"id": "PMID:8743", "title": "Nicotinic acid in the treatment of schizophrenias. Practical and theoretical considerations.", "content": "After reviewing the literature on nicotinic acid in the treatment of schizophrenia, the authors present the results of the Canadian collaborative study. The data indicate that nicotinic acid has no therapeutic effect of schizophrenia.", "contents": "Nicotinic acid in the treatment of schizophrenias. Practical and theoretical considerations. After reviewing the literature on nicotinic acid in the treatment of schizophrenia, the authors present the results of the Canadian collaborative study. The data indicate that nicotinic acid has no therapeutic effect of schizophrenia."}
{"id": "PMID:8744", "title": "Rebound phenomena in manic patients following physostigmine. Preliminary observations.", "content": "The authors have administered physostigmine intravenously to three hospitalized manic patients on a double-blind basis. All three individuals showed clinical change both during and after the physostigmine period, which can be clearly delineated into three distinct phases. The behavioral modifications occurring during the physostigmine run did not qualitatively alter the underlying mania. The authors focus on 'rebound' phenomena, or post-physostigmine changes, as a possible clinical index with which chemically to characterize the initial state of amine imbalance responsible for a given affective illness. The data are considered consistent with an adrenergic-dopaminergic-cholinergic balance hypothesis of affective disorders, and may provide a relevant link in understanding the interface or crossover between manic and schizo-affective illness.", "contents": "Rebound phenomena in manic patients following physostigmine. Preliminary observations. The authors have administered physostigmine intravenously to three hospitalized manic patients on a double-blind basis. All three individuals showed clinical change both during and after the physostigmine period, which can be clearly delineated into three distinct phases. The behavioral modifications occurring during the physostigmine run did not qualitatively alter the underlying mania. The authors focus on 'rebound' phenomena, or post-physostigmine changes, as a possible clinical index with which chemically to characterize the initial state of amine imbalance responsible for a given affective illness. The data are considered consistent with an adrenergic-dopaminergic-cholinergic balance hypothesis of affective disorders, and may provide a relevant link in understanding the interface or crossover between manic and schizo-affective illness."}
{"id": "PMID:8745", "title": "Schedule of protein ingestion and circadian rhythm of certain hepatic enzyme activities involved in glucose metabolism in the rat.", "content": "The circadian rhythms of liver glycogen, plasma glucose, corticosterone and insulin, and hepatic activity of PK, G6PDH, ME, Ac, CoA carbox. PEP-CK and GPT were studied in adult rats. Animals either received a mixed diet ad libitum (8% protein) or a protein meal (1.1 g protein) given at 05:00 or 17:00 h, with free access to a protein-free diet (separately fed). When the protein meal was ingested during the lighted period (17:00) the 24-hour average level of liver PEP-CK was greater than in rats consuming protein during darkness (05:00). In the latter case, modification of the circadian rhythm of liver glycogen and of circadian rhythm of liver PK, G6PDH, ME and Ac.CoA carbox. activity (increase of 24 h average level, extension of period of high activity, sudden increase after ingestion of protein meal) were observed. Conversely, the circadian rhythm of plasma insulin and corticosterone and of liver PEP-CK and GPT activity were only slightly affected by the mode of feeding.", "contents": "Schedule of protein ingestion and circadian rhythm of certain hepatic enzyme activities involved in glucose metabolism in the rat. The circadian rhythms of liver glycogen, plasma glucose, corticosterone and insulin, and hepatic activity of PK, G6PDH, ME, Ac, CoA carbox. PEP-CK and GPT were studied in adult rats. Animals either received a mixed diet ad libitum (8% protein) or a protein meal (1.1 g protein) given at 05:00 or 17:00 h, with free access to a protein-free diet (separately fed). When the protein meal was ingested during the lighted period (17:00) the 24-hour average level of liver PEP-CK was greater than in rats consuming protein during darkness (05:00). In the latter case, modification of the circadian rhythm of liver glycogen and of circadian rhythm of liver PK, G6PDH, ME and Ac.CoA carbox. activity (increase of 24 h average level, extension of period of high activity, sudden increase after ingestion of protein meal) were observed. Conversely, the circadian rhythm of plasma insulin and corticosterone and of liver PEP-CK and GPT activity were only slightly affected by the mode of feeding."}
{"id": "PMID:8748", "title": "The antihypertensive action of several beta-adrenoreceptor-blocking drugs.", "content": "The antihypertensive and pulse-slowing effects of racemic propranolol, oxprenolol, pindolol, practolol and d-propranolol were assessed in 54 hypertensive patients. Drug dosage was selected to be proportionate to beta-adrenoreceptor-blocking potency; d-propranolol dosage equalled approximately that of racemic propranolol. D-propranolol had onlyslight antihypertensive effect; the four other drugs were found to have a considerable and approximately equal antihypertensive effect. The degree of slowing of heart rate varied with the different drugs, being greatest with racemic propanolol. The effect on pulse rate did not correlate with the effect on blood pressure for most of the drugs. The falls in blood pressure induced by racemic propanolol were strongly correlated with those induced by each of the other drugs. The small falls in blood pressured induced by d-propranolol correlated also with those induced by practolol (which had no membrane activity) and are presumably due to its weak beta-adrenoreceptor-blocking action. The beta-adrenoreceptor-blocking action per se is responsible for the antihypertensive action of these drugs.", "contents": "The antihypertensive action of several beta-adrenoreceptor-blocking drugs. The antihypertensive and pulse-slowing effects of racemic propranolol, oxprenolol, pindolol, practolol and d-propranolol were assessed in 54 hypertensive patients. Drug dosage was selected to be proportionate to beta-adrenoreceptor-blocking potency; d-propranolol dosage equalled approximately that of racemic propranolol. D-propranolol had onlyslight antihypertensive effect; the four other drugs were found to have a considerable and approximately equal antihypertensive effect. The degree of slowing of heart rate varied with the different drugs, being greatest with racemic propanolol. The effect on pulse rate did not correlate with the effect on blood pressure for most of the drugs. The falls in blood pressure induced by racemic propanolol were strongly correlated with those induced by each of the other drugs. The small falls in blood pressured induced by d-propranolol correlated also with those induced by practolol (which had no membrane activity) and are presumably due to its weak beta-adrenoreceptor-blocking action. The beta-adrenoreceptor-blocking action per se is responsible for the antihypertensive action of these drugs."}
{"id": "PMID:8749", "title": "A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline.", "content": "The study undertook to compare the efficacy of dibenzepin and amitriptyline in the treatment of endogenous depression. The outcome of the study was that both drugs appear to be equally effective in the treatment of depression, but dibenzepin was more efficient in reducing associated anxiety. Both drugs are appropriate to the treatment of psychotic depression, and work equally rapid. There was also a tendency for dibenzepin to elicit less intense side effects.", "contents": "A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline. The study undertook to compare the efficacy of dibenzepin and amitriptyline in the treatment of endogenous depression. The outcome of the study was that both drugs appear to be equally effective in the treatment of depression, but dibenzepin was more efficient in reducing associated anxiety. Both drugs are appropriate to the treatment of psychotic depression, and work equally rapid. There was also a tendency for dibenzepin to elicit less intense side effects."}
{"id": "PMID:8750", "title": "The rational use of anxiolytics.", "content": "The prescribing of anxiolytics is often a hit-and-miss process. Current knowledge is examined to encourage a more rational use of such drugs. Because the common symptoms occur in a great array of illnesses, diagnosis is of first importance. For the transient situational disturbance drugs may be unnecessary or may be used merely for a day or two. If the anxiety state persists for a month or so the illness might be termed an anxiety neurosis and if there is no accompanying depression, a short course of benzodiazepine may be of value. With depression present to more than a mild degree as part of the neurosis the tricyclic antidepressant doxepin usually achieves better results than a benzodiazepine. Imipramine can be helpful for the phobic anxiety syndrome and monoamine-oxidase inhibitors can be of separate utility. If the anxiety and depression occur in the context of alcoholism, thioridazine and amitriptyline have certain advantages. There is very little place for phenothiazines or other antipsychotic agents in low doses in the therapy of anxiety except for thioridazine in the above indication.", "contents": "The rational use of anxiolytics. The prescribing of anxiolytics is often a hit-and-miss process. Current knowledge is examined to encourage a more rational use of such drugs. Because the common symptoms occur in a great array of illnesses, diagnosis is of first importance. For the transient situational disturbance drugs may be unnecessary or may be used merely for a day or two. If the anxiety state persists for a month or so the illness might be termed an anxiety neurosis and if there is no accompanying depression, a short course of benzodiazepine may be of value. With depression present to more than a mild degree as part of the neurosis the tricyclic antidepressant doxepin usually achieves better results than a benzodiazepine. Imipramine can be helpful for the phobic anxiety syndrome and monoamine-oxidase inhibitors can be of separate utility. If the anxiety and depression occur in the context of alcoholism, thioridazine and amitriptyline have certain advantages. There is very little place for phenothiazines or other antipsychotic agents in low doses in the therapy of anxiety except for thioridazine in the above indication."}
{"id": "PMID:8752", "title": "Fractures of the foot in children.", "content": "Fractures of the foot in children are less common than in adults and are due to severe trauma in which associated injuries may take precedence. Disturbances of growth can occur, usually when there is associated soft tissue damage. Because remodeling of the long bones of the foot does not always correct marked displacement, adequate reduction should be sought to prevent subsequent foot discomfort. Open fractures of the foot deserve considerable care. Primary closure of the wounds should be avoided.", "contents": "Fractures of the foot in children. Fractures of the foot in children are less common than in adults and are due to severe trauma in which associated injuries may take precedence. Disturbances of growth can occur, usually when there is associated soft tissue damage. Because remodeling of the long bones of the foot does not always correct marked displacement, adequate reduction should be sought to prevent subsequent foot discomfort. Open fractures of the foot deserve considerable care. Primary closure of the wounds should be avoided."}
{"id": "PMID:8755", "title": "Spectrophotometric characteristics of bilirubin.", "content": "Spectrophotometric characteristics of bilirubin at low concentrations (0.005-2.500 mg/100 ml) have been studied under various physical conditions in order to gain a better understanding of the state of bilirubin when preparing \"solutions\" for laboratory use. Standing, minimal shaking, or stirring of the bilirubin preparations at pH 7.4 progressively reduced and altered the maximal spectral absorption of bilirubin (440 nm) in aqueous buffered media. The shift to 415-420 nm is attributed to oxidation of the pigment whereas shoulder formation is attributed to the formation of large size particles (flocculants). In the presence of antixidants (L-ascorbic acid and nitrogen gas) and EDTA the maximal absorption peak remained at 440 nm but decreased in magnitude concomitant with development of progressively increasing shoulder at 480-560 nm. In the absence of antioxidants and EDTA maximal absorption shifted to 415-420 nm and the magnitude of 480-560 nm shoulder formation was less. At the higher concentrations of bilirubin and with reduction in pH of the buffer in the absence of antioxidants, the shift to lower wave lengths was reduced and 450-560 nm shoulder formation was increased. In the absence of antioxidants and EDTA at the lower concentrations of bilirubin and in more alkaline media, the reduction at 440 nm and the shift of maximal absorption to the shorter wave lengths was enhanced. At pH 12, stirring of antioxidant-EDTA-containing solutions of bilirubin resulted in neither a shift of maximal absorption to the shorter wave lengths nor the formation of 480-560 nm shoulder. The formation of 480-560 nm shoulder was accompanied by the visual appearance of turbidity. The formation of flocculants when a \"solution\" is agitated indicates that significant portions of the pigment were in fact, not in solution and must have existed previously as a finely dispersed colloidal sol or supersaturated solution which progressed to a colloidal sol. Spectral curves of bilirubin, therefore, may represent a composite resulting from four physical states of bilirubin: (1) bilirubin truly in solution with the spectral peak at 440 nm; (2) bilirubin in the fine colloidal dispersion with spectral characteristics similar to those of bilirubin in solution; (3) bilirubin flocculant giving 480-560 nm shoulder; and (4) oxidation products of bilirubin with the spectral peaks lower than 440 nm. Increasing the pH of the aqueous media containing bilirubin (0.05 mg/100 ml) from 7.4 to 12.0 increased the molar extinction coefficient of bilirubin, E1M/440 1cm, progressively to a maximum at pH 12 of 6.35 X 10(4). Very dilute bilirubin preparations (0.005-0.050 mg/100 ml) in aqueous media, pH 7.4, exhibited spectral evidence of rapid oxidation (more so at higher pH), but spectral shoulder formation was still observed after mechanical agitation. Thus, the solubility of bilirubin in 0.1 M phosphate buffer at pH 7.4 appears to be less than 0.005 mg/100 ml.", "contents": "Spectrophotometric characteristics of bilirubin. Spectrophotometric characteristics of bilirubin at low concentrations (0.005-2.500 mg/100 ml) have been studied under various physical conditions in order to gain a better understanding of the state of bilirubin when preparing \"solutions\" for laboratory use. Standing, minimal shaking, or stirring of the bilirubin preparations at pH 7.4 progressively reduced and altered the maximal spectral absorption of bilirubin (440 nm) in aqueous buffered media. The shift to 415-420 nm is attributed to oxidation of the pigment whereas shoulder formation is attributed to the formation of large size particles (flocculants). In the presence of antixidants (L-ascorbic acid and nitrogen gas) and EDTA the maximal absorption peak remained at 440 nm but decreased in magnitude concomitant with development of progressively increasing shoulder at 480-560 nm. In the absence of antioxidants and EDTA maximal absorption shifted to 415-420 nm and the magnitude of 480-560 nm shoulder formation was less. At the higher concentrations of bilirubin and with reduction in pH of the buffer in the absence of antioxidants, the shift to lower wave lengths was reduced and 450-560 nm shoulder formation was increased. In the absence of antioxidants and EDTA at the lower concentrations of bilirubin and in more alkaline media, the reduction at 440 nm and the shift of maximal absorption to the shorter wave lengths was enhanced. At pH 12, stirring of antioxidant-EDTA-containing solutions of bilirubin resulted in neither a shift of maximal absorption to the shorter wave lengths nor the formation of 480-560 nm shoulder. The formation of 480-560 nm shoulder was accompanied by the visual appearance of turbidity. The formation of flocculants when a \"solution\" is agitated indicates that significant portions of the pigment were in fact, not in solution and must have existed previously as a finely dispersed colloidal sol or supersaturated solution which progressed to a colloidal sol. Spectral curves of bilirubin, therefore, may represent a composite resulting from four physical states of bilirubin: (1) bilirubin truly in solution with the spectral peak at 440 nm; (2) bilirubin in the fine colloidal dispersion with spectral characteristics similar to those of bilirubin in solution; (3) bilirubin flocculant giving 480-560 nm shoulder; and (4) oxidation products of bilirubin with the spectral peaks lower than 440 nm. Increasing the pH of the aqueous media containing bilirubin (0.05 mg/100 ml) from 7.4 to 12.0 increased the molar extinction coefficient of bilirubin, E1M/440 1cm, progressively to a maximum at pH 12 of 6.35 X 10(4). Very dilute bilirubin preparations (0.005-0.050 mg/100 ml) in aqueous media, pH 7.4, exhibited spectral evidence of rapid oxidation (more so at higher pH), but spectral shoulder formation was still observed after mechanical agitation. Thus, the solubility of bilirubin in 0.1 M phosphate buffer at pH 7.4 appears to be less than 0.005 mg/100 ml."}
{"id": "PMID:8756", "title": "Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin.", "content": "For more than 30 years, penicillin has been the agent of choice for pneumococcal infections. During this time the majority of strains of Streptococcus pneumoniae have been highly susceptible to penicillin. However, during the last ten years there have been sporadic reports of pneumococci with increased resistance to penicillin. The case report of an 18-month-old white boy with meningitis due to a strain of S. pneumoniae with increased resistance to penicillin is presented. The MIC of the organism to penicillin was 0.2 mug/ml and the MBC 0.39 mug/ml. The patient had normal immunity and no demonstrable sequestered focus of infection but failed to respond to appropriate doses of intravenous penicillin. Treatment with chloramphenicol caused a dramatic bacteriologic and clinical response. This experience reemphasizes the existence of pneumococcal strains of intermediate penicillin sensitivity and the importance of in vitro susceptibility tests.", "contents": "Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin. For more than 30 years, penicillin has been the agent of choice for pneumococcal infections. During this time the majority of strains of Streptococcus pneumoniae have been highly susceptible to penicillin. However, during the last ten years there have been sporadic reports of pneumococci with increased resistance to penicillin. The case report of an 18-month-old white boy with meningitis due to a strain of S. pneumoniae with increased resistance to penicillin is presented. The MIC of the organism to penicillin was 0.2 mug/ml and the MBC 0.39 mug/ml. The patient had normal immunity and no demonstrable sequestered focus of infection but failed to respond to appropriate doses of intravenous penicillin. Treatment with chloramphenicol caused a dramatic bacteriologic and clinical response. This experience reemphasizes the existence of pneumococcal strains of intermediate penicillin sensitivity and the importance of in vitro susceptibility tests."}
{"id": "PMID:8759", "title": "An exploratory investigation of the personality correlates of aging using the Hand Test.", "content": "The Hand Test was administered to 27 older adults of both sexes (Mage = 66.56) to investigate possible changes in personality concomitant with normal aging. To control partially for such factors as cultural influences and intelligence differences a matched-pair design was used in which the test protocols of the older adults were matched with those of their children of the same sex (Mage = 36.44). Though the Hand Test has not been independently validated on older adults, results were consistent with past findings using projective techniques inasmuch as depletion and constriction of personality were noted. Criticisms of research on the clinical assessment of the elderly were discussed.", "contents": "An exploratory investigation of the personality correlates of aging using the Hand Test. The Hand Test was administered to 27 older adults of both sexes (Mage = 66.56) to investigate possible changes in personality concomitant with normal aging. To control partially for such factors as cultural influences and intelligence differences a matched-pair design was used in which the test protocols of the older adults were matched with those of their children of the same sex (Mage = 36.44). Though the Hand Test has not been independently validated on older adults, results were consistent with past findings using projective techniques inasmuch as depletion and constriction of personality were noted. Criticisms of research on the clinical assessment of the elderly were discussed."}
{"id": "PMID:8760", "title": "H in cortical peritubular capillaries of rat kidney.", "content": "The pH of peritubular capillaries was measured by means of antimony microelectrodes, during their perfusion with mammalian Ringer's solutions at different pH, in control and acetazolamide infused rats. In capillaries perfused with a solution more acid than blood, significant alkalinization was observed at increasing distances from the point of perfusion, while during perfusions with more alkaline solutions, acidification was observed. Plotting the pH change observed per micrometer of distance from the perfusion point against the pH of the perfusing solution, the pH in equilibrium with tubular cells was interpolated. A value of 7.51 +/- 0.01 was found for control rats, significantly higher than the mean arterial blood pH of this group, of 7.39. In acetazolamide infused rats an equilibrium pH of 7.44 +/- 0.02 was found, still higher than the blood pH of 7.34. The slope of these lines was significantly greater in control than in acetazolamide treated rats. This slope was shown to evaluate permeability to the ions responsible for acid-base balance. The present data suggest that peritubular alkalinization is reduced after carbonic anhydrase inhibition due to decreased peritubular permeability to the involved ions, which represents a further site of action of these inhibitors.", "contents": "H in cortical peritubular capillaries of rat kidney. The pH of peritubular capillaries was measured by means of antimony microelectrodes, during their perfusion with mammalian Ringer's solutions at different pH, in control and acetazolamide infused rats. In capillaries perfused with a solution more acid than blood, significant alkalinization was observed at increasing distances from the point of perfusion, while during perfusions with more alkaline solutions, acidification was observed. Plotting the pH change observed per micrometer of distance from the perfusion point against the pH of the perfusing solution, the pH in equilibrium with tubular cells was interpolated. A value of 7.51 +/- 0.01 was found for control rats, significantly higher than the mean arterial blood pH of this group, of 7.39. In acetazolamide infused rats an equilibrium pH of 7.44 +/- 0.02 was found, still higher than the blood pH of 7.34. The slope of these lines was significantly greater in control than in acetazolamide treated rats. This slope was shown to evaluate permeability to the ions responsible for acid-base balance. The present data suggest that peritubular alkalinization is reduced after carbonic anhydrase inhibition due to decreased peritubular permeability to the involved ions, which represents a further site of action of these inhibitors."}
{"id": "PMID:8761", "title": "Physostigmine-induced contractures in frog skeletal muscle.", "content": "Physostigmine in 15 mM concentration at pH 8.4 produces reversible contractures of up to 0.3 Po tension output in frog's whole toe muscle or in 7-10 fiber bundles of these muscles, At pH 7.2, the 15 mM physostigmine contracture output is only about 0.10 Po. The 15 mM, pH 8.4 contractures are essentially unaffected by lack of external Ca2+, complete depolarization of the fibers, detubulation by glycerol treatment, and 0 degrees C ambient temperature. These results and other evidence indicate that physostigmine produces contracture by directly releasing activator Ca2+ from the sarcoplasmic reticulum (SR). Pretreatment of muscles with 4 mM procaine reduces physostigmine's capacity to produce contracture, evidently by means of a competitive inhibition at SR sites. The above results indicate similarities between physostagmine and caffeine contractures. But the physostigmine action differs in that it is reversible, and, especially, it lacks the ability, strongly characteristic of caffeine, to sensitize a muscle to produce a rapid cooling contracture. The internal action of physostigmine requires that it be permeant, and, since it is a weak base (pKa = 8.2), this property is provided by its uncharged base. But, once internal, where the pH = 6.8, most of the drug will be protonated and it may act on the SR in this form, in contrast with caffeine which, since its pKa is about 1.0, acts on the SR as uncharged base.", "contents": "Physostigmine-induced contractures in frog skeletal muscle. Physostigmine in 15 mM concentration at pH 8.4 produces reversible contractures of up to 0.3 Po tension output in frog's whole toe muscle or in 7-10 fiber bundles of these muscles, At pH 7.2, the 15 mM physostigmine contracture output is only about 0.10 Po. The 15 mM, pH 8.4 contractures are essentially unaffected by lack of external Ca2+, complete depolarization of the fibers, detubulation by glycerol treatment, and 0 degrees C ambient temperature. These results and other evidence indicate that physostigmine produces contracture by directly releasing activator Ca2+ from the sarcoplasmic reticulum (SR). Pretreatment of muscles with 4 mM procaine reduces physostigmine's capacity to produce contracture, evidently by means of a competitive inhibition at SR sites. The above results indicate similarities between physostagmine and caffeine contractures. But the physostigmine action differs in that it is reversible, and, especially, it lacks the ability, strongly characteristic of caffeine, to sensitize a muscle to produce a rapid cooling contracture. The internal action of physostigmine requires that it be permeant, and, since it is a weak base (pKa = 8.2), this property is provided by its uncharged base. But, once internal, where the pH = 6.8, most of the drug will be protonated and it may act on the SR in this form, in contrast with caffeine which, since its pKa is about 1.0, acts on the SR as uncharged base."}
{"id": "PMID:8762", "title": "The effect of Ca2+ on the metarhodopsin I-II transition. I. Experiments.", "content": "The effect of Ca2+ on kinetics and equilibrium of the Meta I-II transition was studied in rhodopsin-digitonin-solutions using flash-photometry. With increasing Ca2+-concentrations the Meta I-II-equilibrium is shifted to Meta I. The pH-dependence of the Meta I-II equilibrium is suppressed by Ca2+. To obtain the same effect as with bivalent cations about the 10-fold concentration of univalent ions is required. Ca2+-ions have also an effect on the rate of equilibrating Meta I-II: with increasing Ca2+-concentration the rate-constants of the rapid and slow component decrease and become equal to the value at pH8. This observation can be described as an inhibition of the catalytic effect of protons by Ca2+. Similar results are obtained with Mg2+, whereas K+ and Na+ are practically ineffective. In the presence of the Ca2+-blocking agents verapamil (Isoptin) and D-600 the rate of equilibrating Meta I-II is reduced. These and several former observations can be explained by a model in which the Meta I-II transition is coupled with the separation of negative fixed charges, which can be clamped by Ca2+.", "contents": "The effect of Ca2+ on the metarhodopsin I-II transition. I. Experiments. The effect of Ca2+ on kinetics and equilibrium of the Meta I-II transition was studied in rhodopsin-digitonin-solutions using flash-photometry. With increasing Ca2+-concentrations the Meta I-II-equilibrium is shifted to Meta I. The pH-dependence of the Meta I-II equilibrium is suppressed by Ca2+. To obtain the same effect as with bivalent cations about the 10-fold concentration of univalent ions is required. Ca2+-ions have also an effect on the rate of equilibrating Meta I-II: with increasing Ca2+-concentration the rate-constants of the rapid and slow component decrease and become equal to the value at pH8. This observation can be described as an inhibition of the catalytic effect of protons by Ca2+. Similar results are obtained with Mg2+, whereas K+ and Na+ are practically ineffective. In the presence of the Ca2+-blocking agents verapamil (Isoptin) and D-600 the rate of equilibrating Meta I-II is reduced. These and several former observations can be explained by a model in which the Meta I-II transition is coupled with the separation of negative fixed charges, which can be clamped by Ca2+."}
{"id": "PMID:8763", "title": "The effect of Ca2+ on the metarhodopsin I-II transition. II. Model calculations and hypothesis on a molecular mechanism of visual excitation.", "content": "The model for the effect of Ca2+ on the Meta I-II transition (cf. Part I) is formulated quantitatively and in detail. The clamping forces of Ca2+, which shift the equilibrium to the closed MI-conformation, are taken into account in the law of mass action by a higher value for the association constant of Ca2+ with MI than with MII. Thus the main features of the experimental curves of delta MII-absorption-change as a function of Ca2+- and H+-concentration can be reproduced by a few simple association equilibria. The agreement can be improved by calculating with a conformative coupling between two rhodopsin molecules. In a further modification of the model also the observed increase of delta MII in the alkaline beyond pH 9 is reproduced. Finally, the models lead to an opening and closing mechanism for a Ca2+-permeable pore across the disc membrane, thus contributing to a hypothesis of visual excitation.", "contents": "The effect of Ca2+ on the metarhodopsin I-II transition. II. Model calculations and hypothesis on a molecular mechanism of visual excitation. The model for the effect of Ca2+ on the Meta I-II transition (cf. Part I) is formulated quantitatively and in detail. The clamping forces of Ca2+, which shift the equilibrium to the closed MI-conformation, are taken into account in the law of mass action by a higher value for the association constant of Ca2+ with MI than with MII. Thus the main features of the experimental curves of delta MII-absorption-change as a function of Ca2+- and H+-concentration can be reproduced by a few simple association equilibria. The agreement can be improved by calculating with a conformative coupling between two rhodopsin molecules. In a further modification of the model also the observed increase of delta MII in the alkaline beyond pH 9 is reproduced. Finally, the models lead to an opening and closing mechanism for a Ca2+-permeable pore across the disc membrane, thus contributing to a hypothesis of visual excitation."}
{"id": "PMID:8764", "title": "Further investigations on the effect of denervation and pH on the conductance change at the neuromuscular junction of the frog.", "content": "Currents induced by acetylcholine application at the voltage-calmped frog end-plate, were measured over a large range of membrane potentials. Due to a non-linearity of the current-voltage curve, the directly-measured reversal potential may be quite different from the value classically determined by extrapolation (linear regression) of the measurements made at potentials below spike threshold. Denervation and changes of external pH were found to alter the shape of the current-voltage relation, but not the directly-measured reversal potential. These effects are tentatively explained on the basis of changes in the ratio: time-to-peak for [ACh] reaching the receptors/mean life-time of the open synaptic channels. Possible changes in cooperativity are also considered.", "contents": "Further investigations on the effect of denervation and pH on the conductance change at the neuromuscular junction of the frog. Currents induced by acetylcholine application at the voltage-calmped frog end-plate, were measured over a large range of membrane potentials. Due to a non-linearity of the current-voltage curve, the directly-measured reversal potential may be quite different from the value classically determined by extrapolation (linear regression) of the measurements made at potentials below spike threshold. Denervation and changes of external pH were found to alter the shape of the current-voltage relation, but not the directly-measured reversal potential. These effects are tentatively explained on the basis of changes in the ratio: time-to-peak for [ACh] reaching the receptors/mean life-time of the open synaptic channels. Possible changes in cooperativity are also considered."}
{"id": "PMID:8765", "title": "Force velocity relations in vascular smooth muscle: the influence of pH, pCa, and noradrenaline.", "content": "The kinetics of vascular smooth musclw activity was studied by means of afterloaded isotonic contractions of the tetanized rat portal vein at varied pH (8.0-5.9), pCa (3.4-2.1), and during noradrenaline incubation (0.4 mug/ml). Under control conditions (pH 7.3, pCa 2.6) the following parameters of the force velocity relation were calculated: a of Hill's equation (relating to the isometric peak tension) = 0.36; b (relating to the actual muscle length) = 0.19 ML/s; VM Trelating to the actual muscle length) = 0.56 ML/s. Within the range of pCa between 2.0 and 3.2 the amount of force generation (= delta P) depended on the extracellular calcium level whereas the extrapolated velocity of shortening of the unloaded preparation (= VM) did not. Also pH changes between 8.0 and 6.8 as well as noradrenaline incubation at a pH of 5.9 affected delta P quite considerably, but VM only scarcely. At a pH of 6.3, however, VM was distinctly diminished, and a reduced calcium sensitivity of the ATPase was inferred from the shift of ED50 of extracellular calcium from 0.66 mM Ca at a pH of 7.3 to 1.56 mM Ca at a pH of 6.3 (P less than 0.0005). It is concluded from these results that the experimental conditions-pCa between 2.0 and 3.2, pH between 8.0 and 6.8, and noradrenaline added at a pH of 5.9-obviously change the intracellular calcium concentration which influences the number of activated interaction sites rather than the velocity of crossbridge movement.", "contents": "Force velocity relations in vascular smooth muscle: the influence of pH, pCa, and noradrenaline. The kinetics of vascular smooth musclw activity was studied by means of afterloaded isotonic contractions of the tetanized rat portal vein at varied pH (8.0-5.9), pCa (3.4-2.1), and during noradrenaline incubation (0.4 mug/ml). Under control conditions (pH 7.3, pCa 2.6) the following parameters of the force velocity relation were calculated: a of Hill's equation (relating to the isometric peak tension) = 0.36; b (relating to the actual muscle length) = 0.19 ML/s; VM Trelating to the actual muscle length) = 0.56 ML/s. Within the range of pCa between 2.0 and 3.2 the amount of force generation (= delta P) depended on the extracellular calcium level whereas the extrapolated velocity of shortening of the unloaded preparation (= VM) did not. Also pH changes between 8.0 and 6.8 as well as noradrenaline incubation at a pH of 5.9 affected delta P quite considerably, but VM only scarcely. At a pH of 6.3, however, VM was distinctly diminished, and a reduced calcium sensitivity of the ATPase was inferred from the shift of ED50 of extracellular calcium from 0.66 mM Ca at a pH of 7.3 to 1.56 mM Ca at a pH of 6.3 (P less than 0.0005). It is concluded from these results that the experimental conditions-pCa between 2.0 and 3.2, pH between 8.0 and 6.8, and noradrenaline added at a pH of 5.9-obviously change the intracellular calcium concentration which influences the number of activated interaction sites rather than the velocity of crossbridge movement."}
{"id": "PMID:8766", "title": "pH sensitivity of cells located at the ventrolateral surface of the cat medulla oblongata in vitro.", "content": "pH sensitivity of cells located at the ventral surface of the medulla oblongata was examined in a thin brain slice of the cat in vitro and the following results were obtained: (1) Transmembrane potential of the surface cells located in the area medial to the XIIth cranial nerve was reduced slightly by application of low pH solution; (2) In the rostral part of the area medial to the XIIth cranial nerve regular neuronal discharges could be observed extracellularly. The rate of firing of these cells was increased by lowering the external pH. These results were considered to support the idea the H+ receptor cells may exist in the surface layer of the ventral medulla.", "contents": "pH sensitivity of cells located at the ventrolateral surface of the cat medulla oblongata in vitro. pH sensitivity of cells located at the ventral surface of the medulla oblongata was examined in a thin brain slice of the cat in vitro and the following results were obtained: (1) Transmembrane potential of the surface cells located in the area medial to the XIIth cranial nerve was reduced slightly by application of low pH solution; (2) In the rostral part of the area medial to the XIIth cranial nerve regular neuronal discharges could be observed extracellularly. The rate of firing of these cells was increased by lowering the external pH. These results were considered to support the idea the H+ receptor cells may exist in the surface layer of the ventral medulla."}
{"id": "PMID:8770", "title": "A compact form of double-stranded RNA in solutions containing poly(ethyleneglycol).", "content": "Molecules of single-stranded ribosomal RNA and double-stranded replicative form of phage f2 RNA (dsRNA) adopt a compact form in solutions, containing sufficiently high concentrations of salt (NaCl) and polymer (PEG). However, only in the cases of native dsRNA molecules the compact particles are characterized by a regular internal structure, which accounts for the appearance of an intense positive band in CD spectra. Heating or acidification of PEG-containing solutions of dsRNA leads to the disappearance of the intense positive CD band, which results from the \"destruction\" of the regular internal structure of compact particles. Comparison of properties of DNA and dsRNA compact particles formed in PEG-containing water-salt solutions suggests the existence of similar mechanisms of compactization of double-stranded polynucleotides.", "contents": "A compact form of double-stranded RNA in solutions containing poly(ethyleneglycol). Molecules of single-stranded ribosomal RNA and double-stranded replicative form of phage f2 RNA (dsRNA) adopt a compact form in solutions, containing sufficiently high concentrations of salt (NaCl) and polymer (PEG). However, only in the cases of native dsRNA molecules the compact particles are characterized by a regular internal structure, which accounts for the appearance of an intense positive band in CD spectra. Heating or acidification of PEG-containing solutions of dsRNA leads to the disappearance of the intense positive CD band, which results from the \"destruction\" of the regular internal structure of compact particles. Comparison of properties of DNA and dsRNA compact particles formed in PEG-containing water-salt solutions suggests the existence of similar mechanisms of compactization of double-stranded polynucleotides."}
{"id": "PMID:8771", "title": "Protonated polynucleotide structures, 20. Interaction between poly(dG)-poly(dC) and poly(rC).1.", "content": "A study of the interaction between poly(dG)-poly(dC) and poly(rC) demonstrates that, at neutral pH and high ionic strength, there is replacement of the dC strand by poly(rC). At acid pH, formation of a triple-stranded complex which equally may involve the replacement phenomenon is observed. There is no evidence for interaction at neutral pH between poly(dG)-poly(dC) and oligo(rC), while a three-stranded complex is formed at acid pH. These data are consistent with the studies of comparative stabilities of double stranded deoxy or ribo polymers and deoxy-ribo hybrids.", "contents": "Protonated polynucleotide structures, 20. Interaction between poly(dG)-poly(dC) and poly(rC).1. A study of the interaction between poly(dG)-poly(dC) and poly(rC) demonstrates that, at neutral pH and high ionic strength, there is replacement of the dC strand by poly(rC). At acid pH, formation of a triple-stranded complex which equally may involve the replacement phenomenon is observed. There is no evidence for interaction at neutral pH between poly(dG)-poly(dC) and oligo(rC), while a three-stranded complex is formed at acid pH. These data are consistent with the studies of comparative stabilities of double stranded deoxy or ribo polymers and deoxy-ribo hybrids."}
{"id": "PMID:8772", "title": "Affinity labelling of phenylalanyl-tRNA synthetase from E. coli MRE-600 by E. coli tRNAphe containing photoreactive group.", "content": "The photoinduced reaction of phenylalanyl-tRNA synthetase (E.C.6.1.1.20) from E.coli MRE-600 with tRNAphe containing photoreative p-N3-C6H4-NHCOCH2-group attached to 4-thiouridine sU8 (azido-tRNAphe) was investigated. The attachment of this group does not influence the dissociation constant of the complex of Phe-tRNAphe with the enzyme, however it results in sevenfold increase of Km in the enzymatic aminoacylation of tRNAphe. Under irradiation at 300 nm at pH 5.8 the covalent binding of [14C]-Phe-azido-tRNAphe to the enzyme takes place 0.3 moles of the reagent being attached per mole of the enzyme. tRNA prevents the reaction. Phenylalanine, ATP,ADP,AMP, adenosine and pyrophosphate (2.5 xx 10(-3) M) don't affect neither the stability of the tRNA-enzyme complex nor the rate of the affinity labelling. The presence of the mixture of either phenylalanine or phenylalaninol with ATP as well as phenylalaninol adenylate exhibits 50% inhibition of the photoinduced reaction. Therefore, the reaction of [14C]-Phe-azido-tRNA with the enzyme is significantly less sensitive to the presence of the ligands than the reaction of chlorambucilyl-tRNA with the reactive group attached to the acceptor end of the tRNA studied in 1. It has been concluded that the kinetics of the affinity labelling does permit to discriminate the influence of the low molecular weight ligands of the enzyme on the different sites of the tRNA enzyme interaction.", "contents": "Affinity labelling of phenylalanyl-tRNA synthetase from E. coli MRE-600 by E. coli tRNAphe containing photoreactive group. The photoinduced reaction of phenylalanyl-tRNA synthetase (E.C.6.1.1.20) from E.coli MRE-600 with tRNAphe containing photoreative p-N3-C6H4-NHCOCH2-group attached to 4-thiouridine sU8 (azido-tRNAphe) was investigated. The attachment of this group does not influence the dissociation constant of the complex of Phe-tRNAphe with the enzyme, however it results in sevenfold increase of Km in the enzymatic aminoacylation of tRNAphe. Under irradiation at 300 nm at pH 5.8 the covalent binding of [14C]-Phe-azido-tRNAphe to the enzyme takes place 0.3 moles of the reagent being attached per mole of the enzyme. tRNA prevents the reaction. Phenylalanine, ATP,ADP,AMP, adenosine and pyrophosphate (2.5 xx 10(-3) M) don't affect neither the stability of the tRNA-enzyme complex nor the rate of the affinity labelling. The presence of the mixture of either phenylalanine or phenylalaninol with ATP as well as phenylalaninol adenylate exhibits 50% inhibition of the photoinduced reaction. Therefore, the reaction of [14C]-Phe-azido-tRNA with the enzyme is significantly less sensitive to the presence of the ligands than the reaction of chlorambucilyl-tRNA with the reactive group attached to the acceptor end of the tRNA studied in 1. It has been concluded that the kinetics of the affinity labelling does permit to discriminate the influence of the low molecular weight ligands of the enzyme on the different sites of the tRNA enzyme interaction."}
{"id": "PMID:8769", "title": "[Latent renal tubular acidosis of the cirrhotic patient. Study of urinary excretion of protons and sodium].", "content": "Patients suffering from hepatic cirrhosis develop renal tubular acidosis when subjected to an acid overload. This is characterised by a fall in plasma pH and bicarbonate and by inability of the kidney to lower urine pH and to excrete a sufficient quantity of protons in the form of titratable acidy and ammonia. This disturbance is difficult to explain. It may form part of the picture of the classical functional renal insufficiency of the cirrhotic and may be a particular result of altered renal haemodynamics. Detected by the acidification test, this abnormality may be demonstrated in the absence of any other involvement of renal function. The severity of this renal tubular acidosis would appear to be related to the degree of hepatic disease.", "contents": "[Latent renal tubular acidosis of the cirrhotic patient. Study of urinary excretion of protons and sodium]. Patients suffering from hepatic cirrhosis develop renal tubular acidosis when subjected to an acid overload. This is characterised by a fall in plasma pH and bicarbonate and by inability of the kidney to lower urine pH and to excrete a sufficient quantity of protons in the form of titratable acidy and ammonia. This disturbance is difficult to explain. It may form part of the picture of the classical functional renal insufficiency of the cirrhotic and may be a particular result of altered renal haemodynamics. Detected by the acidification test, this abnormality may be demonstrated in the absence of any other involvement of renal function. The severity of this renal tubular acidosis would appear to be related to the degree of hepatic disease."}
{"id": "PMID:8767", "title": "[Cytological, etiological and prognostic aspects of male infertility. Attempt at classification apropos of 1,303 cases].", "content": "Study of 1303 cases of male sub-fertility led to a certain number of practical conclusions: - From a diagnostic viewpoint, the \"fertility\" of an individual, which is difficult to assess, depends more on the motility than the number of spermatozoa. This is most faithfully reflected in the crossed penetration test which defines the quality of penetration of a control mucus. The value of electron microscopic cytological study in the case of total asthenospermia or major monomorphous teratospermia, reflecting an irreversible constitutional abnormality of the ultrastructure of the spermatozoon, is emphasised. - From a therapeutic viewpoint, recent progress has involved the technique of surgical treatment for varicocoele as well as hormone therapy. It is essential not to neglect empirical \"minor aids\" indicated in the case of unexplained abnormalities (homologous artifical insemination in the case of abnormalities in the volume of the ejaculate, retard androgen therapy in the case of polyzoospermia). - From a prognostic viewpoint. The distinction must be drawn between aetiologies of good prognosis (80% of our success) responsible for transient abnormalities in spermatogenesis (infections, metabolic disturbances, varicocoele) and aetiologies with an unfavourable prognosis since they cause tubulopathies of greater or lesser severity with a lesional impairment of spermatogenesis.", "contents": "[Cytological, etiological and prognostic aspects of male infertility. Attempt at classification apropos of 1,303 cases]. Study of 1303 cases of male sub-fertility led to a certain number of practical conclusions: - From a diagnostic viewpoint, the \"fertility\" of an individual, which is difficult to assess, depends more on the motility than the number of spermatozoa. This is most faithfully reflected in the crossed penetration test which defines the quality of penetration of a control mucus. The value of electron microscopic cytological study in the case of total asthenospermia or major monomorphous teratospermia, reflecting an irreversible constitutional abnormality of the ultrastructure of the spermatozoon, is emphasised. - From a therapeutic viewpoint, recent progress has involved the technique of surgical treatment for varicocoele as well as hormone therapy. It is essential not to neglect empirical \"minor aids\" indicated in the case of unexplained abnormalities (homologous artifical insemination in the case of abnormalities in the volume of the ejaculate, retard androgen therapy in the case of polyzoospermia). - From a prognostic viewpoint. The distinction must be drawn between aetiologies of good prognosis (80% of our success) responsible for transient abnormalities in spermatogenesis (infections, metabolic disturbances, varicocoele) and aetiologies with an unfavourable prognosis since they cause tubulopathies of greater or lesser severity with a lesional impairment of spermatogenesis."}
{"id": "PMID:8774", "title": "Management of muscle cramps in hemodialysis patients. Controlled prospective study.", "content": "In conclusion, a blind, prospective study demonstrated that HS was the most effective way of treating muscle cramps induced by hemodialysis. Hypertonic non-electrolyte solutions were less effective. The chance of a placebo effect in these patients is about 13.0%.", "contents": "Management of muscle cramps in hemodialysis patients. Controlled prospective study. In conclusion, a blind, prospective study demonstrated that HS was the most effective way of treating muscle cramps induced by hemodialysis. Hypertonic non-electrolyte solutions were less effective. The chance of a placebo effect in these patients is about 13.0%."}
{"id": "PMID:8775", "title": "Guanosine 3':5'-cyclic monophosphate binding proteins in rat tissues.", "content": "Rat tissues were surveyed for proteins which bind cGMP. Binding activity was high in extracts of lung, cerebellum, and small intestine, but was low in those of liver, adipose tissue, and skeletal muscle. DEAE-cellulose chromatography resolved two peaks of cGMP-binding activity in most tissues. The binding protein in peak 1 was eluted in the flow-through volume and was most abundant in extracts of intestine. It had a sedimentation coefficient of 6S and was highly specific for cGMP at pH 7.0 (dissociation constant KD=0.05 muM). No cGMP-dependent histone kinase activity was found for this peak. The binding protein in peak 2 was eluted by 0.05-0.15 M NaCl and was the predominant binding substance in lung, cerebellum, and heart. It had a sedimentation coefficient of 8S and binding was also highly specific for cGMP, with a KD of 0.05 muM. This peak of binding activity was associated with cGMP-dependent protein kinase activity which could be purified approximately 200-fold by Sepharose 6B chromatography. Cyclic GMP dependency of kinase activity was observed only at low histone concentrations. The abundance of one or both the above binding proteins correlated with the known basal levels of cGMP in the tissues.", "contents": "Guanosine 3':5'-cyclic monophosphate binding proteins in rat tissues. Rat tissues were surveyed for proteins which bind cGMP. Binding activity was high in extracts of lung, cerebellum, and small intestine, but was low in those of liver, adipose tissue, and skeletal muscle. DEAE-cellulose chromatography resolved two peaks of cGMP-binding activity in most tissues. The binding protein in peak 1 was eluted in the flow-through volume and was most abundant in extracts of intestine. It had a sedimentation coefficient of 6S and was highly specific for cGMP at pH 7.0 (dissociation constant KD=0.05 muM). No cGMP-dependent histone kinase activity was found for this peak. The binding protein in peak 2 was eluted by 0.05-0.15 M NaCl and was the predominant binding substance in lung, cerebellum, and heart. It had a sedimentation coefficient of 8S and binding was also highly specific for cGMP, with a KD of 0.05 muM. This peak of binding activity was associated with cGMP-dependent protein kinase activity which could be purified approximately 200-fold by Sepharose 6B chromatography. Cyclic GMP dependency of kinase activity was observed only at low histone concentrations. The abundance of one or both the above binding proteins correlated with the known basal levels of cGMP in the tissues."}
{"id": "PMID:8776", "title": "Subunit structure and isozymic forms of gamma-glutamyl transpeptidase.", "content": "gamma-Glutamyl transpeptidase is associated with the membranes of a number of epithelial and lymphoid cells. When the enzyme is isolated from rat kidney by a method involving detergent extraction and affinity chromatography, an aggregate of molecular weight greater than 200,000 (heavy form) is obtained. Treatment of the heavy form with bromelain yields a light form of the enzyme (molecular weight of approximately 68,000), which is separable by isoelectric focusing into 12 enzymatically active isozymes which are very similar with respect to catalytic behavior, content of amino acids, hexoses, and aminohexoses, but which differ significantly in sialic acid content. Treatment with neuraminidase converts the acidic isozymes to more basic forms. Each isozyme dissociates in sodium dodecyl sulfate into two nonidentical glycopeptides (molecular weights of 46,000 and 22,000) which can be cross-linked with dimethylsuberimidate to yield a species with an apparent molecular weight of 70,000, which indicates that the isozymes are dimers. Physical and immunological studies indicate that the heavy form of the enzyme contains the dimeric light form as well as other membrane proteins.", "contents": "Subunit structure and isozymic forms of gamma-glutamyl transpeptidase. gamma-Glutamyl transpeptidase is associated with the membranes of a number of epithelial and lymphoid cells. When the enzyme is isolated from rat kidney by a method involving detergent extraction and affinity chromatography, an aggregate of molecular weight greater than 200,000 (heavy form) is obtained. Treatment of the heavy form with bromelain yields a light form of the enzyme (molecular weight of approximately 68,000), which is separable by isoelectric focusing into 12 enzymatically active isozymes which are very similar with respect to catalytic behavior, content of amino acids, hexoses, and aminohexoses, but which differ significantly in sialic acid content. Treatment with neuraminidase converts the acidic isozymes to more basic forms. Each isozyme dissociates in sodium dodecyl sulfate into two nonidentical glycopeptides (molecular weights of 46,000 and 22,000) which can be cross-linked with dimethylsuberimidate to yield a species with an apparent molecular weight of 70,000, which indicates that the isozymes are dimers. Physical and immunological studies indicate that the heavy form of the enzyme contains the dimeric light form as well as other membrane proteins."}
{"id": "PMID:8777", "title": "Differential degradation of messenger RNAs in mammalian cells.", "content": "Through the use of an assay that measures cellular capacity for specific enzyme synthesis, mRNA of alanine aminotransferase (EC 2.6.1.2; L-alanine:2-oxoglutarate aminotransferase) was found to be degraded with a half-life of 12-14 hr in cultured Reuber H-35 cells; mRNA of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) has a half-life of 2 hr in the same cells. Rates of degradation of the mRNAs are the same whether new mRNA accumulation is blocked by removal of the steroid inducer or by inhibition of mRNA synthesis (actinomycin). Cycloheximide inhibits the normally rapid turnover of tyrosine aminotransferase mRNA, but agents such as puromycin and sodium fluoride, which disrupt polysome structure, do not alter the turnover rate of the tyrosine and alanine aminotransferase mRNAs. The tyrosine and alanine aminotransferase mRNAs appear to be translated at equivalent rates. The data suggest that the degradation rate of these two mRNAs is determined by the polynucleotide structure of the mRNA molecules at or near the site for ribosome binding and initiation.", "contents": "Differential degradation of messenger RNAs in mammalian cells. Through the use of an assay that measures cellular capacity for specific enzyme synthesis, mRNA of alanine aminotransferase (EC 2.6.1.2; L-alanine:2-oxoglutarate aminotransferase) was found to be degraded with a half-life of 12-14 hr in cultured Reuber H-35 cells; mRNA of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) has a half-life of 2 hr in the same cells. Rates of degradation of the mRNAs are the same whether new mRNA accumulation is blocked by removal of the steroid inducer or by inhibition of mRNA synthesis (actinomycin). Cycloheximide inhibits the normally rapid turnover of tyrosine aminotransferase mRNA, but agents such as puromycin and sodium fluoride, which disrupt polysome structure, do not alter the turnover rate of the tyrosine and alanine aminotransferase mRNAs. The tyrosine and alanine aminotransferase mRNAs appear to be translated at equivalent rates. The data suggest that the degradation rate of these two mRNAs is determined by the polynucleotide structure of the mRNA molecules at or near the site for ribosome binding and initiation."}
{"id": "PMID:8778", "title": "Dual role of Zn2+ as inhibitor and activator of fructose 1,6-bisphosphatase of rat liver.", "content": "At neutral pH, Zn2+ is a potent and specific inhibitor of rat liver fructose 1,6-bisphosphatase (EC 3.1.3.11; D-fructose-1,6-bisphosphate 1-phosphohydrolase). Inhibition by Zn2+ is uncompetitive with respect to the activating cations Mg2+ and Mn2+, and the kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 muM. At higher concentrations (about 10(-5) M) Zn2+, and to a lesser extent Co2+, function as activating cations. Binding studies show that the enzyme binds two equivalents of Zn2+ per subunit; one equivalent is partially displaced by Mg2+ and is presumably bound to the site for activating cations. A second equivalent binds to the high-affinity site, presumably identical to the inhibitory site. The results suggest that Zn2+ functions as an allosteric regulator, and that the commonly observed activation of fructose 1,6-bisphosphatase at neutral pH by EDTA, histidine, and other chelators is due to removal of endogenous Zn2+ by these agents.", "contents": "Dual role of Zn2+ as inhibitor and activator of fructose 1,6-bisphosphatase of rat liver. At neutral pH, Zn2+ is a potent and specific inhibitor of rat liver fructose 1,6-bisphosphatase (EC 3.1.3.11; D-fructose-1,6-bisphosphate 1-phosphohydrolase). Inhibition by Zn2+ is uncompetitive with respect to the activating cations Mg2+ and Mn2+, and the kinetic data suggest that the enzyme possesses a distinct high-affinity binding site for Zn2+, with Ki of approximately 0.3 muM. At higher concentrations (about 10(-5) M) Zn2+, and to a lesser extent Co2+, function as activating cations. Binding studies show that the enzyme binds two equivalents of Zn2+ per subunit; one equivalent is partially displaced by Mg2+ and is presumably bound to the site for activating cations. A second equivalent binds to the high-affinity site, presumably identical to the inhibitory site. The results suggest that Zn2+ functions as an allosteric regulator, and that the commonly observed activation of fructose 1,6-bisphosphatase at neutral pH by EDTA, histidine, and other chelators is due to removal of endogenous Zn2+ by these agents."}
{"id": "PMID:8779", "title": "Binding of [3H]dihydroazapetine to alpha-adrenoreceptor-related proteins from rat vas deferens.", "content": "The potent alpha-adrenoreceptor blocking agent, azapetine, has been catalytically reduced with tritium gas to form [3H]dihydroazapetine. [3H]Dihydroazapetine retains significant ability to block alpha-adrenoreceptors and has been used as a ligand to study the receptor in a subcellular fraction containing membrane fragments from rat vas deferens. Specific binding of [3H]dihydroazapetine rapidly reaches equilibrium and is also reversible and saturable with a dissociation constant similar to that determined pharmacologically. The binding capacity is approximately 40 pmol/mg of protein. All alpha-adrenergic blockers tested were able to inhibit specific binding. High concentrations of alprenolol, atropine, or chlorpheniramine had no effect. In addition, all alpha-adrenergic agonists of the imidazoline class inhibit binding in low concentrations, whereas soterenol or carbamylcholine did not. There is good correlation (r=0.84) between blockade or stimulation of the receptor in intact tissues and inhibition of binding of [3H]dihydroazapetine to the subcellular fraction. These findings suggest that the fraction contains alpha-adrenoreceptor-related proteins. Alpha-adrenergic agonists structurally related to norepinephrine caused a stereoselective increase in binding in favor of the (-)-isomer, possibly reflecting an allosteric interaction at a different binding site on the receptor protein. The possibility of two different modes of binding for structurally dissimilar agonists is suggested.", "contents": "Binding of [3H]dihydroazapetine to alpha-adrenoreceptor-related proteins from rat vas deferens. The potent alpha-adrenoreceptor blocking agent, azapetine, has been catalytically reduced with tritium gas to form [3H]dihydroazapetine. [3H]Dihydroazapetine retains significant ability to block alpha-adrenoreceptors and has been used as a ligand to study the receptor in a subcellular fraction containing membrane fragments from rat vas deferens. Specific binding of [3H]dihydroazapetine rapidly reaches equilibrium and is also reversible and saturable with a dissociation constant similar to that determined pharmacologically. The binding capacity is approximately 40 pmol/mg of protein. All alpha-adrenergic blockers tested were able to inhibit specific binding. High concentrations of alprenolol, atropine, or chlorpheniramine had no effect. In addition, all alpha-adrenergic agonists of the imidazoline class inhibit binding in low concentrations, whereas soterenol or carbamylcholine did not. There is good correlation (r=0.84) between blockade or stimulation of the receptor in intact tissues and inhibition of binding of [3H]dihydroazapetine to the subcellular fraction. These findings suggest that the fraction contains alpha-adrenoreceptor-related proteins. Alpha-adrenergic agonists structurally related to norepinephrine caused a stereoselective increase in binding in favor of the (-)-isomer, possibly reflecting an allosteric interaction at a different binding site on the receptor protein. The possibility of two different modes of binding for structurally dissimilar agonists is suggested."}
{"id": "PMID:8780", "title": "beta-endorphin is a potent analgesic agent.", "content": "beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its actions are blocked by the specific opiate antagonist, naloxone hydrochloride. The activity of beta-endorphin in vivo is also compared to other peptides that show opiate-like activity in assays in vitro.", "contents": "beta-endorphin is a potent analgesic agent. beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its actions are blocked by the specific opiate antagonist, naloxone hydrochloride. The activity of beta-endorphin in vivo is also compared to other peptides that show opiate-like activity in assays in vitro."}
{"id": "PMID:8781", "title": "Evoked neurotransmitter release: statistical effects of nonuniformity and nonstationarity.", "content": "Recent studies of the mechanism of quantal neurotransmitter release have assumed that the number of quanta released at each stimulation is binomially distributed and have sought to estimate the binomial parameters n and p. Mathematical analysis and computer simulations show that temporal variation in the number of eligible or filled release sites and either spatial or temporal variation in the probability of release at a site can drastically bias such estimates, while the experimental histograms remain statistically indistinguishable from those predicted by the binomial law. Interpretation of the estimates n and p in terms of ultrastructural or physiological characteristics of the nerve terminal is liable to significant error if departures from the binomial assumptions are not suitably assessed.", "contents": "Evoked neurotransmitter release: statistical effects of nonuniformity and nonstationarity. Recent studies of the mechanism of quantal neurotransmitter release have assumed that the number of quanta released at each stimulation is binomially distributed and have sought to estimate the binomial parameters n and p. Mathematical analysis and computer simulations show that temporal variation in the number of eligible or filled release sites and either spatial or temporal variation in the probability of release at a site can drastically bias such estimates, while the experimental histograms remain statistically indistinguishable from those predicted by the binomial law. Interpretation of the estimates n and p in terms of ultrastructural or physiological characteristics of the nerve terminal is liable to significant error if departures from the binomial assumptions are not suitably assessed."}
{"id": "PMID:8784", "title": "The in vitro adsorption of some antibiotics on antacids.", "content": "The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents.", "contents": "The in vitro adsorption of some antibiotics on antacids. The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents."}
{"id": "PMID:8793", "title": "Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 2: Mechanism of 5.5-diallylbarbituric acid degradation as a function of pH.", "content": "Allobarbital degradation products, produced in its aqueous solutions at different pH values, were noted by t.l.c., isolated and identified. The identification of several intermediates and the kinetic work previously done were assumed to enable one to elucidate the mechanism of the process studied.", "contents": "Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 2: Mechanism of 5.5-diallylbarbituric acid degradation as a function of pH. Allobarbital degradation products, produced in its aqueous solutions at different pH values, were noted by t.l.c., isolated and identified. The identification of several intermediates and the kinetic work previously done were assumed to enable one to elucidate the mechanism of the process studied."}
{"id": "PMID:8794", "title": "Migration of amphetamine and mandelic and salicylic acids in various pH buffer solutions examined via thin layer electrophoresis.", "content": "The degree of migration of optically active, racemic and non-optically active acids and bases on cellulose, silica gel and alumina thin layers is examined in various pH buffer solutions using thin layer electrophoresis. The results indicate different mobilities of the acidic and basic compounds in the various pH buffers of the experiment.", "contents": "Migration of amphetamine and mandelic and salicylic acids in various pH buffer solutions examined via thin layer electrophoresis. The degree of migration of optically active, racemic and non-optically active acids and bases on cellulose, silica gel and alumina thin layers is examined in various pH buffer solutions using thin layer electrophoresis. The results indicate different mobilities of the acidic and basic compounds in the various pH buffers of the experiment."}
{"id": "PMID:8796", "title": "Comparisons between the antianesthetic action of dibutyryl cyclic AMP and analeptic drugs on amobarbital-induced narcosis in the rat.", "content": "The dose-related antianesthetic and antidotal property of dibutyryl cyclic AMP, devoid of toxic effects, imparts uniqueness to the nucleotide as an arousal agent. Of the analeptic drugs studied (d-amphetamine, picrotoxin, pentylenetetrazol, caffeine, theophylline, strychnine, ethamivan and doxapram), only picrotoxin demonstrated antianesthetic properties. However, picrotoxin was associated with severe toxicity at all dose levels tested. No analeptic drug is effective in reversing the central nervous system depression produced by sedative, hypnotic or tranquilizer drug overdosage.", "contents": "Comparisons between the antianesthetic action of dibutyryl cyclic AMP and analeptic drugs on amobarbital-induced narcosis in the rat. The dose-related antianesthetic and antidotal property of dibutyryl cyclic AMP, devoid of toxic effects, imparts uniqueness to the nucleotide as an arousal agent. Of the analeptic drugs studied (d-amphetamine, picrotoxin, pentylenetetrazol, caffeine, theophylline, strychnine, ethamivan and doxapram), only picrotoxin demonstrated antianesthetic properties. However, picrotoxin was associated with severe toxicity at all dose levels tested. No analeptic drug is effective in reversing the central nervous system depression produced by sedative, hypnotic or tranquilizer drug overdosage."}
{"id": "PMID:8797", "title": "Acetylsecohemicholinium: chemical and pharmacological evaluation of an open-ring hemicholinium.", "content": "Acetylsecohemicholinium No. 3 (AcHC-3), the acetate of the open ring (seco form of hemicholinium No. 3, HC-3) hydrolyzes in vitro to the hemiacetal HC-3 at pH values above 9, a temperature-dependent conversion illustrated by ultraviolet spectral shifts from 305 to 257 mmu, and to a limited extent by certain esterases as measured by manometric analysis. An LD50 of 125 mug/kg for a neutral solution of AcHC-3 was decreased to 78.3 mug/kg (the LD50 of HC-3) upon being made basic. Prolonged treatment of mice with LD10-20 doses of AcHC-3 was associated with decreased fatty acid oxidation in the liver and resulted in infiltration of fat into hepatic cells, a reaction preventable by treatment with small doses of choline (10 mg/kg). AcHC-3 causes neuromuscular and autonomic ganglionic blockade, cholinesterase inhibition, and in vitro inhibition of acetylcholine (ACh) synthesis. These actions, although HC-3-like, appear to be due to AcHC-3 rather than HC-3 since neither cholinesterase inhibition nor hepatic ligation altered the neuromuscular blocking actions of AcHC-3. In addition to its HC-3-like properties, AcHC-3 consistently produced a transient increase in twitch height of gastrocnemius muscle before blockade and was dose-responsive in depressing blood pressure and in eliciting contractions of the isolated guinea pig ileum. AcHC-3 is both a cholinomimetic (depresses arterial blood pressure, decreases heart rate and increases ileal contractions) and a competitor of acetylcholine. That is, in most preparations tested, AcHC-3 at lower concentrations has as much intrinsic activity as ACh and at somewhat higher concentrations competitively blocks the responses to ACh. These cholinomimetic actions may be due to the presence of two ACh moieties on the AcHC-3 molecule which attach to cholinergic receptor sites. Also noted was an action of AcHC-3 that seems to be peculiar to the secohemicholiniums, namely, the potentiation of catechloamines.", "contents": "Acetylsecohemicholinium: chemical and pharmacological evaluation of an open-ring hemicholinium. Acetylsecohemicholinium No. 3 (AcHC-3), the acetate of the open ring (seco form of hemicholinium No. 3, HC-3) hydrolyzes in vitro to the hemiacetal HC-3 at pH values above 9, a temperature-dependent conversion illustrated by ultraviolet spectral shifts from 305 to 257 mmu, and to a limited extent by certain esterases as measured by manometric analysis. An LD50 of 125 mug/kg for a neutral solution of AcHC-3 was decreased to 78.3 mug/kg (the LD50 of HC-3) upon being made basic. Prolonged treatment of mice with LD10-20 doses of AcHC-3 was associated with decreased fatty acid oxidation in the liver and resulted in infiltration of fat into hepatic cells, a reaction preventable by treatment with small doses of choline (10 mg/kg). AcHC-3 causes neuromuscular and autonomic ganglionic blockade, cholinesterase inhibition, and in vitro inhibition of acetylcholine (ACh) synthesis. These actions, although HC-3-like, appear to be due to AcHC-3 rather than HC-3 since neither cholinesterase inhibition nor hepatic ligation altered the neuromuscular blocking actions of AcHC-3. In addition to its HC-3-like properties, AcHC-3 consistently produced a transient increase in twitch height of gastrocnemius muscle before blockade and was dose-responsive in depressing blood pressure and in eliciting contractions of the isolated guinea pig ileum. AcHC-3 is both a cholinomimetic (depresses arterial blood pressure, decreases heart rate and increases ileal contractions) and a competitor of acetylcholine. That is, in most preparations tested, AcHC-3 at lower concentrations has as much intrinsic activity as ACh and at somewhat higher concentrations competitively blocks the responses to ACh. These cholinomimetic actions may be due to the presence of two ACh moieties on the AcHC-3 molecule which attach to cholinergic receptor sites. Also noted was an action of AcHC-3 that seems to be peculiar to the secohemicholiniums, namely, the potentiation of catechloamines."}
{"id": "PMID:8798", "title": "The anatomy of neurosecretory neurones in the pond snail Lymnaea stagnalis (L.).", "content": "The anatomy of three neurosecretory cell types in the central nervous system (c.n.s.) of the gastropod mollusc Lymnaea stagnalis (L.)- the Dark Green Cells, Yellow Cells and Yellow-green Cells-has been studied by using bright and dark field illumination of material stained for neurosecretion by the Alcian Blue-Alcian Yellow technique. The neuronal geometry of single and groups of neurosecretory cells of the various types has been reconstructed from serial sections, and the likely destination of most of their processes has been determined. Dark Green Cells are monopolar, occur exclusively within the central nervous system (c.n.s.), have few or no branches terminating in neuropile, and send axons to the surface of the pleuro-parietal and pleuro-cerebral connectives. The majority of Dark Green Cell axons however (80-85%), project down nerves which innervate ventral and anterior parts of the head-foot, the neck and the mantle. Dark Green Cell axons can be found in small nerves throughout these areas, and may terminate in a find plexus of axons on the surfaces of the nerves. Since previous experimental work has shown that the Dark Green Cells are involved in osmotic or ionic regulation, these results suggest that the target organ of the Dark Green Cells may be the skin. Yellow Cells occur both within and outside the c.n.s. They are usually monopolar, but can be bipolar. They have several axons which normally arise separately from a single pole of the cell body, or close to it. One or more processes leave the cell proximal to the point where separate axons arise, and may run unbranched for some distance through neuropile before terminating in fine brances and blobs of various sizes. These branches may release hormone inside the c.n.s. Yellow-green Cells are mono-, bi- or multi-polar, and like the Yellow Cells are found both within and outside the c.n.s. Some Yellow-green Cells, though not all, have projections which terminate in neuropile in fine branches and blobs. Yellow-green Cell bodies which occur in nerves can project back along the nerve into the c.n.s. The axons of Yellow Cells and Yellow-green Cells project to release sites in various ways. Some project into the connective tissue shealth of the c.n.s., which serves as a neurohaemal organ, either directly through the surface of a ganglion, or from the pleuro-cerebral or pleuro-parietal connectives. Other axons leave the c.n.s. via nerves leaving the left and right parietal and visceral ganglia; projections into the intestinal, anal, and internal right parietal nerves being most numerous. Axons which may be from either, or both Yellow Cells and Yellow-green Cells, can be found along the entire unbranched lengths of these nerves, and in subsequent branches which innervate organs lying in the anterior turn of the shell. All of these orgnas are closely associated with the lung cavity...", "contents": "The anatomy of neurosecretory neurones in the pond snail Lymnaea stagnalis (L.). The anatomy of three neurosecretory cell types in the central nervous system (c.n.s.) of the gastropod mollusc Lymnaea stagnalis (L.)- the Dark Green Cells, Yellow Cells and Yellow-green Cells-has been studied by using bright and dark field illumination of material stained for neurosecretion by the Alcian Blue-Alcian Yellow technique. The neuronal geometry of single and groups of neurosecretory cells of the various types has been reconstructed from serial sections, and the likely destination of most of their processes has been determined. Dark Green Cells are monopolar, occur exclusively within the central nervous system (c.n.s.), have few or no branches terminating in neuropile, and send axons to the surface of the pleuro-parietal and pleuro-cerebral connectives. The majority of Dark Green Cell axons however (80-85%), project down nerves which innervate ventral and anterior parts of the head-foot, the neck and the mantle. Dark Green Cell axons can be found in small nerves throughout these areas, and may terminate in a find plexus of axons on the surfaces of the nerves. Since previous experimental work has shown that the Dark Green Cells are involved in osmotic or ionic regulation, these results suggest that the target organ of the Dark Green Cells may be the skin. Yellow Cells occur both within and outside the c.n.s. They are usually monopolar, but can be bipolar. They have several axons which normally arise separately from a single pole of the cell body, or close to it. One or more processes leave the cell proximal to the point where separate axons arise, and may run unbranched for some distance through neuropile before terminating in fine brances and blobs of various sizes. These branches may release hormone inside the c.n.s. Yellow-green Cells are mono-, bi- or multi-polar, and like the Yellow Cells are found both within and outside the c.n.s. Some Yellow-green Cells, though not all, have projections which terminate in neuropile in fine branches and blobs. Yellow-green Cell bodies which occur in nerves can project back along the nerve into the c.n.s. The axons of Yellow Cells and Yellow-green Cells project to release sites in various ways. Some project into the connective tissue shealth of the c.n.s., which serves as a neurohaemal organ, either directly through the surface of a ganglion, or from the pleuro-cerebral or pleuro-parietal connectives. Other axons leave the c.n.s. via nerves leaving the left and right parietal and visceral ganglia; projections into the intestinal, anal, and internal right parietal nerves being most numerous. Axons which may be from either, or both Yellow Cells and Yellow-green Cells, can be found along the entire unbranched lengths of these nerves, and in subsequent branches which innervate organs lying in the anterior turn of the shell. All of these orgnas are closely associated with the lung cavity..."}
{"id": "PMID:8799", "title": "The rectal complex in the larvae of lepidoptera.", "content": "In the so-called \"cryptonephric\" condition of the excretory system in insects the distal ends of the Malpighian tubules are closely applied to the rectum and enclosed with it in a special chamber, the perinephric space, separated from the rest of the body cavity by the perinephric membrane. The term \"rectal complex\" refers to this association of tubules and rectum, which is found in the larvae (but not in the adults) of most Lepidoptera. In the mealworm (Coleoptera) the rectal complex has notable ability to remove water from the faeces, but this ability is not conspicuously developed in the larvae of the two species of Lepidoptera here studied: Pieris brassicae and Manduca sexta. On the other hand these larvae have notable ability to maintain salt balance under heavy dietary loading, and in this the rectal complex plays an important part. A study of salt balance in more detail has shown that more sodium can be eliminated in the faeces than enters the rectal complex from the intestine. Consideration of other possible routes of entry points strongly to the Malpighian tubules. Superimposed upon a new flow of tubule fluid out of the rectal complex there is a tidal flow, brought about by the rectal musculature and amplified by dilatations of the cryptonephric tubules, which could bring in fluid from the free tubules and afford opportunity for the uptake of salts. Evidence is presented in support of this view. This tidal flow of tubule fluid and uptake of salts could be the basis of the build-up of high osmolarity in the perinephric fluid and could contribute to the removal of water from the faeces. It could also be the basic mechanism in the mealworm, the leptophragmal mechanism being superimposed upon it.", "contents": "The rectal complex in the larvae of lepidoptera. In the so-called \"cryptonephric\" condition of the excretory system in insects the distal ends of the Malpighian tubules are closely applied to the rectum and enclosed with it in a special chamber, the perinephric space, separated from the rest of the body cavity by the perinephric membrane. The term \"rectal complex\" refers to this association of tubules and rectum, which is found in the larvae (but not in the adults) of most Lepidoptera. In the mealworm (Coleoptera) the rectal complex has notable ability to remove water from the faeces, but this ability is not conspicuously developed in the larvae of the two species of Lepidoptera here studied: Pieris brassicae and Manduca sexta. On the other hand these larvae have notable ability to maintain salt balance under heavy dietary loading, and in this the rectal complex plays an important part. A study of salt balance in more detail has shown that more sodium can be eliminated in the faeces than enters the rectal complex from the intestine. Consideration of other possible routes of entry points strongly to the Malpighian tubules. Superimposed upon a new flow of tubule fluid out of the rectal complex there is a tidal flow, brought about by the rectal musculature and amplified by dilatations of the cryptonephric tubules, which could bring in fluid from the free tubules and afford opportunity for the uptake of salts. Evidence is presented in support of this view. This tidal flow of tubule fluid and uptake of salts could be the basis of the build-up of high osmolarity in the perinephric fluid and could contribute to the removal of water from the faeces. It could also be the basic mechanism in the mealworm, the leptophragmal mechanism being superimposed upon it."}
{"id": "PMID:8800", "title": "Genetic and anthropological studies in the human adaptability section of the International Biological Programme.", "content": "In the U.K. contribution to the H.A. (Human Adaptibility) section of I.B.P., genetic and anthropological studies have focused on three concerns. First, attempts have been made in a number of investigation to gain additional descriptive information about the genetic compostition of the world's populations. Concentrating on blood groups, blood enzymes, serum proteins and other polmorphic markers important gaps have been filled in our knowledge of the geographical paterns of human variation and of the affinities of populations wig and characterizing populations which were being studied for other purposes. For example, it was of critical concern in  interpreting results to know in the investigations of climatic physiology and nutrition in Ethiopia and Israel whether the various groups studied in different environments were genetically the same or not. Finally, attention was focused in a number of investigations, especially those in New Guinea, Tristan da Cunha, Tanzania, and the Orkneys, on the factors which determine the genetic structure of populations. In these the effects of such phenomena as inbreeding, genetic drift, founder effects, migration and gene flow and the relation between genetic variety and health were examined and much attention was given to the interaction between demographic forces and genetics.", "contents": "Genetic and anthropological studies in the human adaptability section of the International Biological Programme. In the U.K. contribution to the H.A. (Human Adaptibility) section of I.B.P., genetic and anthropological studies have focused on three concerns. First, attempts have been made in a number of investigation to gain additional descriptive information about the genetic compostition of the world's populations. Concentrating on blood groups, blood enzymes, serum proteins and other polmorphic markers important gaps have been filled in our knowledge of the geographical paterns of human variation and of the affinities of populations wig and characterizing populations which were being studied for other purposes. For example, it was of critical concern in  interpreting results to know in the investigations of climatic physiology and nutrition in Ethiopia and Israel whether the various groups studied in different environments were genetically the same or not. Finally, attention was focused in a number of investigations, especially those in New Guinea, Tristan da Cunha, Tanzania, and the Orkneys, on the factors which determine the genetic structure of populations. In these the effects of such phenomena as inbreeding, genetic drift, founder effects, migration and gene flow and the relation between genetic variety and health were examined and much attention was given to the interaction between demographic forces and genetics."}
{"id": "PMID:8801", "title": "Nutrition.", "content": "Nutrition appeared somewhat late on the scene in the I.B.P. projects in the U.K., but eventually it occupied an integral part of many of the H.A. (human adaptability) investigations. The nutritional data obtained in the studies of isolated and nearisolated communities in Tristan da Cunha and in New Guinea provided information of wide nutritional significance. There were also detailed and extensive studies in Israel which, similarly to those in New Guinea, attempted to relate nutritional factors to enviroment, working conditions, and physical fitness. Some extraordinarily low energy intakes found in Ethiopians have induced much speculation on the extent which man can adequately adapt to restricted food supplies. Interesting nutritional observations, of general importance, have also arisen from results obtained on such disparate groups as Glasgow adolescents, Tanzanian and Sudanese students, children in Malawi and vegans in the U.K.", "contents": "Nutrition. Nutrition appeared somewhat late on the scene in the I.B.P. projects in the U.K., but eventually it occupied an integral part of many of the H.A. (human adaptability) investigations. The nutritional data obtained in the studies of isolated and nearisolated communities in Tristan da Cunha and in New Guinea provided information of wide nutritional significance. There were also detailed and extensive studies in Israel which, similarly to those in New Guinea, attempted to relate nutritional factors to enviroment, working conditions, and physical fitness. Some extraordinarily low energy intakes found in Ethiopians have induced much speculation on the extent which man can adequately adapt to restricted food supplies. Interesting nutritional observations, of general importance, have also arisen from results obtained on such disparate groups as Glasgow adolescents, Tanzanian and Sudanese students, children in Malawi and vegans in the U.K."}
{"id": "PMID:8802", "title": "Work capacity, thermal responses and lung function: united kingdom studies in the L.B.P.", "content": "Results of physiological studies from some ten U.K. Human Adaptability projects are presented. U.K. investigators made major contributions in developing and adapting techniques for the assussment under field conditions of work capacity, heat tolerance and respiratory function. The various ethnic studies of work capacity revealed the special role of body size and muscularity, as well as training, in determining the observed inter- and intra-population variance. The results on samples from U.K., New Guinea, the Caribbean, Israel, West and East Africa and the Ethiopian highlands gave no indication that genetic difference were significant in determining population differences. Differences in heat tolerance reflect in general the intensity of heat exposure, especially when combined with hard physical work. Indigenous peoples in Africa and New Guinea show some modification in sweating responses which do not appear to be genetically determined but are in some way, as yet not clearly established, attributable to long continued residence in tropical climates. In renal function of some seven ethnic groups were analysed in terms of lung volume bellows function, gas exchange and responses to excercise and carbon dioxide. The relative importance of genetic and non-genetic factors was examined.", "contents": "Work capacity, thermal responses and lung function: united kingdom studies in the L.B.P. Results of physiological studies from some ten U.K. Human Adaptability projects are presented. U.K. investigators made major contributions in developing and adapting techniques for the assussment under field conditions of work capacity, heat tolerance and respiratory function. The various ethnic studies of work capacity revealed the special role of body size and muscularity, as well as training, in determining the observed inter- and intra-population variance. The results on samples from U.K., New Guinea, the Caribbean, Israel, West and East Africa and the Ethiopian highlands gave no indication that genetic difference were significant in determining population differences. Differences in heat tolerance reflect in general the intensity of heat exposure, especially when combined with hard physical work. Indigenous peoples in Africa and New Guinea show some modification in sweating responses which do not appear to be genetically determined but are in some way, as yet not clearly established, attributable to long continued residence in tropical climates. In renal function of some seven ethnic groups were analysed in terms of lung volume bellows function, gas exchange and responses to excercise and carbon dioxide. The relative importance of genetic and non-genetic factors was examined."}
{"id": "PMID:8803", "title": "Food protein sources.", "content": "Work on food, planned by the U.M. (Use and Management) Section of the U.K. committe, was limited to sources of protein because we agreed that more problems calling for research were likely to arise in getting adequate supplies of protein than of other types of food. Deer meat can be produced on land too rough and exposed for sheep; parts of the work on their metabolism and food requirements necessitated building a mobile laboratory. The manner in which the nutritive value of maize is affected by changes in the ratios in which the component proteins are present, stimulated similar studies on barley and groundnut. There is good quality protein in coconuts and leaves but its use in human food is restricted by the presence of fibre. Methods for separating protein from fibre and other deleterious components were improved. In cooperation with scientists in India and Nigeria, the potential yield of protein-deficient foods. e.g. cassava, were 'ennobled' by growing micro-organisms on them with the addition of a cheap source of nitrogen.", "contents": "Food protein sources. Work on food, planned by the U.M. (Use and Management) Section of the U.K. committe, was limited to sources of protein because we agreed that more problems calling for research were likely to arise in getting adequate supplies of protein than of other types of food. Deer meat can be produced on land too rough and exposed for sheep; parts of the work on their metabolism and food requirements necessitated building a mobile laboratory. The manner in which the nutritive value of maize is affected by changes in the ratios in which the component proteins are present, stimulated similar studies on barley and groundnut. There is good quality protein in coconuts and leaves but its use in human food is restricted by the presence of fibre. Methods for separating protein from fibre and other deleterious components were improved. In cooperation with scientists in India and Nigeria, the potential yield of protein-deficient foods. e.g. cassava, were 'ennobled' by growing micro-organisms on them with the addition of a cheap source of nitrogen."}
{"id": "PMID:8804", "title": "Post-embryonic development in the ventral cord of Caenorhabditis elegans.", "content": "56 nerve cells are added to the ventral cord and associated ganglia of Caenorhabditis elegans at about the time of the first larval moult. These cells are produced by the uniform division of 13 neuroblasts followed by a defined pattern of cell deaths. Comparison with the data in the previous paper suggests that there is a relationship between the ancestry of a cell and its function. The significance of programmed cell death is discussed.", "contents": "Post-embryonic development in the ventral cord of Caenorhabditis elegans. 56 nerve cells are added to the ventral cord and associated ganglia of Caenorhabditis elegans at about the time of the first larval moult. These cells are produced by the uniform division of 13 neuroblasts followed by a defined pattern of cell deaths. Comparison with the data in the previous paper suggests that there is a relationship between the ancestry of a cell and its function. The significance of programmed cell death is discussed."}
{"id": "PMID:8805", "title": "The pharynx of Caenorhabditis elegans.", "content": "The anatomy of the pharynx of Caenorhabditis elegans has been reconstructed from electron micrographs of serial sections. The pharynx is used for pumping food into the gut, and is composed of 34 muscle cells, 9 marginal cells, 9 epithelial cells, 5 gland cells and 20 neurones. Three regions of specialization in the cuticle lining of the pharyngeal lumen may aid in the accumulation of food particles. A basement membrane isolates the pharynx from the rest of the animal, making the pharyngeal nervous system a nearly self-contained unit which is composed primarily of five classes of motor neurones and six classes of interneurones. Three other classes have also been described, which by their morphology appear to be neurosecretory and motor, motor and interneuronal, and lastly one pair that only innervates three of the marginal cells. Some classes of neurone have free endings just under the cuticle lining the lumen of the pharynx, suggesting that these are mechano- or proprio-receptive endings. The connectivity of these neurones has been described at the level of individual synaptic regions, and after combining this information with video taped observations of the pharynx pumping, some interpretations of how these neurones function have been offered.", "contents": "The pharynx of Caenorhabditis elegans. The anatomy of the pharynx of Caenorhabditis elegans has been reconstructed from electron micrographs of serial sections. The pharynx is used for pumping food into the gut, and is composed of 34 muscle cells, 9 marginal cells, 9 epithelial cells, 5 gland cells and 20 neurones. Three regions of specialization in the cuticle lining of the pharyngeal lumen may aid in the accumulation of food particles. A basement membrane isolates the pharynx from the rest of the animal, making the pharyngeal nervous system a nearly self-contained unit which is composed primarily of five classes of motor neurones and six classes of interneurones. Three other classes have also been described, which by their morphology appear to be neurosecretory and motor, motor and interneuronal, and lastly one pair that only innervates three of the marginal cells. Some classes of neurone have free endings just under the cuticle lining the lumen of the pharynx, suggesting that these are mechano- or proprio-receptive endings. The connectivity of these neurones has been described at the level of individual synaptic regions, and after combining this information with video taped observations of the pharynx pumping, some interpretations of how these neurones function have been offered."}
{"id": "PMID:8806", "title": "The structure of the ventral nerve cord of Caenorhabditis elegans.", "content": "The nervous system of Caenorhabditis elegans is arranged as a series of fibre bundles which run along internal hypodermal ridges. Most of the sensory integration takes place in a ring of nerve fibres which is wrapped round the pharynx in the head. The body muscles in the head are innervated by motor neurones in this nerve ring while those in the lower part of the body are innervated by a set of motor neurones in a longitudinal fibre bundle which joins the nerve ring, the ventral cord. These motor neurones can be put into five classes on the basis of their morphology and synaptic input. At any one point along the cord only one member from each class has neuromuscular junctions. Members of a given class are arranged in a regular linear sequence in the cord and have non-overlapping fields of motor synaptic activity, the transition between fields of adjacent neurones being sharp and well defined. Members of a given class form gap junctions with neighbouring members of the same class but never to motor neurones of another class. Three of the motor neurone classes receive  their synaptic input from a set of interneurones coming from the nerve ring. These interneurones can in turn be grouped into four classes and each of three motor neurone classes receives its synaptic input from a unique combination of interneurone classes. The possible developmental and functional significance of these observations is discussed.", "contents": "The structure of the ventral nerve cord of Caenorhabditis elegans. The nervous system of Caenorhabditis elegans is arranged as a series of fibre bundles which run along internal hypodermal ridges. Most of the sensory integration takes place in a ring of nerve fibres which is wrapped round the pharynx in the head. The body muscles in the head are innervated by motor neurones in this nerve ring while those in the lower part of the body are innervated by a set of motor neurones in a longitudinal fibre bundle which joins the nerve ring, the ventral cord. These motor neurones can be put into five classes on the basis of their morphology and synaptic input. At any one point along the cord only one member from each class has neuromuscular junctions. Members of a given class are arranged in a regular linear sequence in the cord and have non-overlapping fields of motor synaptic activity, the transition between fields of adjacent neurones being sharp and well defined. Members of a given class form gap junctions with neighbouring members of the same class but never to motor neurones of another class. Three of the motor neurone classes receive  their synaptic input from a set of interneurones coming from the nerve ring. These interneurones can in turn be grouped into four classes and each of three motor neurone classes receives its synaptic input from a unique combination of interneurone classes. The possible developmental and functional significance of these observations is discussed."}
{"id": "PMID:8807", "title": "The ultrastructure of Gymnosphaera albida Sassaki, a marine axopodiate protozoon.", "content": "Gymnosphaera albida has been found on the sponge Sycon ciliatum in the Menai Straits, North Wales, during the months of May to December. It commonly adopts a sedentary mode of life when cultured, settling with its body in contact with the substratum and its axopodia radiating upwards and outwards all round. At times it floats freely. When sessile it can displace itself, but not by rolling. It is a voracious carnivore. The largest seen had a body size of 510 mum X 320 mum. The body of Gymnosphaera is divided into three zones: a central medulla, a cortex and a superficial reticulated pseudopodial layer. The medulla is finely vacuolated and contains an axoplast at its centre. The cortical cytoplasm contains many nuclei, Golgi bodies, polysomes, mitochondria, osmiophilic globules, lipoid spherules and vacuoles of various kinds, but no zooxanthellae. The superficial reticulated pseuopodial layer contains osmiophilic globules and occasional mitochondria. Axonemes radiate from the axoplast to the axopodia, along which osmiophilic globules are generally in motion. In between the cortex and the reticulated pseudopodial layer there is a narrow, extracytoplasmic capsular wall (Sassaki's line), consisting of a microfibrillar coagulum. The wall is a labile structure, perforating locally to allow the passage of food vacuoles or faeces and vanishing completely in certain conditions. It is evaginated to form a sleeve around the base of each axopodium. The cortex is completely penetrated by a system of clefts, the lumen of which opens here and there into the space containing the capsular wall. The clefts are distinct from the endoplasmic reticulum, cisternae of which are commonly found near the surface of the cytoplasmic tracts. Some of the cortical vacuoles contain organic refractive crystals. The crystals have the shape of crossed rodlets, each rodlet having a thermostable component ensheathing a thermolabile component. Their properties are described. The nuclei are enveloped in a thin layer of cytoplasm, connected by narrow bridges to the adjacent cytoplasmic strands. They generally contain several peripherally arranged nucleoli, each bearing a number of nucleolar organizers. Near the centre of the nucleoplasm there is usually a \"central chromatin body\". The vacuoles of the medulla are of two kinds, one equipped with a fibrous coat. In the vicinity of an axoneme the coat commonly connects with the microtubules and their cross-bridges. The axoplast has a central \"hyalosphere\" exhibiting  a fibrogranular matrix. No  tripartite organelle is present therein. The axoplast shell consists of the proximal ends of the axonemes, each enveloped by a fibrous sheath, the fibres coursing around adjacent axonemes, binding them together. The shell thickness is a constant fraction (1/2.5) of the axoplast diameter. The axonemes consist of bundles of parallel microtubules arranged in transverse section in a pattern of alternating rows of hexagons, the microtubules being joined together by 12.3 nm long cross-bridges...", "contents": "The ultrastructure of Gymnosphaera albida Sassaki, a marine axopodiate protozoon. Gymnosphaera albida has been found on the sponge Sycon ciliatum in the Menai Straits, North Wales, during the months of May to December. It commonly adopts a sedentary mode of life when cultured, settling with its body in contact with the substratum and its axopodia radiating upwards and outwards all round. At times it floats freely. When sessile it can displace itself, but not by rolling. It is a voracious carnivore. The largest seen had a body size of 510 mum X 320 mum. The body of Gymnosphaera is divided into three zones: a central medulla, a cortex and a superficial reticulated pseudopodial layer. The medulla is finely vacuolated and contains an axoplast at its centre. The cortical cytoplasm contains many nuclei, Golgi bodies, polysomes, mitochondria, osmiophilic globules, lipoid spherules and vacuoles of various kinds, but no zooxanthellae. The superficial reticulated pseuopodial layer contains osmiophilic globules and occasional mitochondria. Axonemes radiate from the axoplast to the axopodia, along which osmiophilic globules are generally in motion. In between the cortex and the reticulated pseudopodial layer there is a narrow, extracytoplasmic capsular wall (Sassaki's line), consisting of a microfibrillar coagulum. The wall is a labile structure, perforating locally to allow the passage of food vacuoles or faeces and vanishing completely in certain conditions. It is evaginated to form a sleeve around the base of each axopodium. The cortex is completely penetrated by a system of clefts, the lumen of which opens here and there into the space containing the capsular wall. The clefts are distinct from the endoplasmic reticulum, cisternae of which are commonly found near the surface of the cytoplasmic tracts. Some of the cortical vacuoles contain organic refractive crystals. The crystals have the shape of crossed rodlets, each rodlet having a thermostable component ensheathing a thermolabile component. Their properties are described. The nuclei are enveloped in a thin layer of cytoplasm, connected by narrow bridges to the adjacent cytoplasmic strands. They generally contain several peripherally arranged nucleoli, each bearing a number of nucleolar organizers. Near the centre of the nucleoplasm there is usually a \"central chromatin body\". The vacuoles of the medulla are of two kinds, one equipped with a fibrous coat. In the vicinity of an axoneme the coat commonly connects with the microtubules and their cross-bridges. The axoplast has a central \"hyalosphere\" exhibiting  a fibrogranular matrix. No  tripartite organelle is present therein. The axoplast shell consists of the proximal ends of the axonemes, each enveloped by a fibrous sheath, the fibres coursing around adjacent axonemes, binding them together. The shell thickness is a constant fraction (1/2.5) of the axoplast diameter. The axonemes consist of bundles of parallel microtubules arranged in transverse section in a pattern of alternating rows of hexagons, the microtubules being joined together by 12.3 nm long cross-bridges..."}
{"id": "PMID:8808", "title": "Peroxide induced chemiluminescence in an in vitro proline hydroxylation system.", "content": "This communication describes a hydrogen peroxide (HOOH) induced chemiluminescence (CL) in an in vitro aromatic (proline) hydroxylation system. The reactive components of the system are ascorbic (AA), ethylene diamine tetraacetic disodium salt (EDTA), ferrous sulfate, and HOOH. The CL is (1) nearly dissipated within three minutes, (2) enhanced and/or sustained by proline and polylysine to a greater degree than by alanine, (3) partially inhibited by a,a' dipyridyl, EDTA, and ethanol, (4) most dependent upon the presence of Fe2+, AA, and HOOH. The in vitro proline hydroxylation system is more effective than ground state oxygen in terms of the CL produced and the percent of hydroxyproline formed.", "contents": "Peroxide induced chemiluminescence in an in vitro proline hydroxylation system. This communication describes a hydrogen peroxide (HOOH) induced chemiluminescence (CL) in an in vitro aromatic (proline) hydroxylation system. The reactive components of the system are ascorbic (AA), ethylene diamine tetraacetic disodium salt (EDTA), ferrous sulfate, and HOOH. The CL is (1) nearly dissipated within three minutes, (2) enhanced and/or sustained by proline and polylysine to a greater degree than by alanine, (3) partially inhibited by a,a' dipyridyl, EDTA, and ethanol, (4) most dependent upon the presence of Fe2+, AA, and HOOH. The in vitro proline hydroxylation system is more effective than ground state oxygen in terms of the CL produced and the percent of hydroxyproline formed."}
{"id": "PMID:8810", "title": "Voraciousness induced in cats by benzodiazepines.", "content": "Different benzodiazepines, when administered to fasting cats, increased both the total amount of food eaten and also the rate at which food was ingested. Moreover, when injected to foodsatiated cats, these compounds made them resume eating voraciously. Pentobarbital also stimulated food intake, but was much less potent than the benzodiazepines tested.", "contents": "Voraciousness induced in cats by benzodiazepines. Different benzodiazepines, when administered to fasting cats, increased both the total amount of food eaten and also the rate at which food was ingested. Moreover, when injected to foodsatiated cats, these compounds made them resume eating voraciously. Pentobarbital also stimulated food intake, but was much less potent than the benzodiazepines tested."}
{"id": "PMID:8811", "title": "Drug-induced parkinsonism in the rat- a model for biochemical investigation of the parkinson-syndrome. III. The incorporation of D-glucose-14C(U) in amino acids of brain and liver from rats pretreated with reserpine or with phenothiazines.", "content": "Following treatment with reserpine or alternatively with a combination of phenothiazines (Randolektil, Majeptil) a drug-induced parkinsonoid reaction was provoked in rats. Twenty min before decapitation, 18 muCi d-glucose-14C(U) was administered intravenously. Concentration and radioactivities of glutamic acid (glu), glutamine (gln), serine (ser), and glycine (gly) were assayed in some regions of brain and in liver. Separation was performed by a combination of paper electrophoresis and chromatography or by an automatic amino acid analyzer. 1 After reserpine, the concentrations of serine and glycine were increased ten-fold while their specific activities decreased by the same factor. The interconversion serine-glycine was not affected. The concentration of glutamic acid was reduced while its specific activity remained constant. 2. After phenothiazines, the concentrations of serine and glycine in brain were also increased but their specific activities were decreased to a different degree. This indicates an additional effect on the serine-synthesis from glucose. The interconversion serine-glycine was also altered. The concentration of glutamic acid was decreased but specific activity was constant except in the thalamus region tested. 3. The influence of both treatments on amino acid turnover in liver differed from the observed impairment of brain metabolism. 4. Possible correlations between the changes in amino acid metabolism, catecholamines, and the neurologic parkinsonian symptoms are discussed.", "contents": "Drug-induced parkinsonism in the rat- a model for biochemical investigation of the parkinson-syndrome. III. The incorporation of D-glucose-14C(U) in amino acids of brain and liver from rats pretreated with reserpine or with phenothiazines. Following treatment with reserpine or alternatively with a combination of phenothiazines (Randolektil, Majeptil) a drug-induced parkinsonoid reaction was provoked in rats. Twenty min before decapitation, 18 muCi d-glucose-14C(U) was administered intravenously. Concentration and radioactivities of glutamic acid (glu), glutamine (gln), serine (ser), and glycine (gly) were assayed in some regions of brain and in liver. Separation was performed by a combination of paper electrophoresis and chromatography or by an automatic amino acid analyzer. 1 After reserpine, the concentrations of serine and glycine were increased ten-fold while their specific activities decreased by the same factor. The interconversion serine-glycine was not affected. The concentration of glutamic acid was reduced while its specific activity remained constant. 2. After phenothiazines, the concentrations of serine and glycine in brain were also increased but their specific activities were decreased to a different degree. This indicates an additional effect on the serine-synthesis from glucose. The interconversion serine-glycine was also altered. The concentration of glutamic acid was decreased but specific activity was constant except in the thalamus region tested. 3. The influence of both treatments on amino acid turnover in liver differed from the observed impairment of brain metabolism. 4. Possible correlations between the changes in amino acid metabolism, catecholamines, and the neurologic parkinsonian symptoms are discussed."}
{"id": "PMID:8812", "title": "Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics.", "content": "The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever in an operant chamber resulted in reinforcement following the administration of morphine or LSD and the opposite lever was reinforced after saline. After discriminated responding was stable, stimulus generalization tests with narcotic analgesics and antagonists showed that the stimulus properties of morphine generalized to methadone and meperidine, and partially to pentazocine, all of which produce morphine-like subjective effects in humans. Morphine stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine, but not to nalorphine. In humans cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but the subjective effects of cyclazocine are differentiable from those of LSD.", "contents": "Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics. The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever in an operant chamber resulted in reinforcement following the administration of morphine or LSD and the opposite lever was reinforced after saline. After discriminated responding was stable, stimulus generalization tests with narcotic analgesics and antagonists showed that the stimulus properties of morphine generalized to methadone and meperidine, and partially to pentazocine, all of which produce morphine-like subjective effects in humans. Morphine stimulus properties did not generalize to nalorphine or cyclazocine, which produce dissimilar subjective effects. The stimulus properties of LSD generalized partially to cyclazocine, but not to nalorphine. In humans cyclazocine and nalorphine produce a high incidence of psychotomimetic effects, but the subjective effects of cyclazocine are differentiable from those of LSD."}
{"id": "PMID:8813", "title": "A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs.", "content": "The effects of oral, bedtime triazolam 0.5 mg and flurazepam 30 mg, on the laboratory sleep of 12 insomniacs were compared in a double blind, crossover study. A 22 consecutive night schedule was used: Nts. 1--2 placebo; 3--6 first drug; 7--8 placebo; 9--14 no drugs; 15--16 placebo; 17--20 second drug; 21--22 placebo. In 6 Ss first drug was triazolam and second drug was flurazepam. In the other 6 Ss the drug order was reversed. Effects on sleep were assessed objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by physical exams, clinical lab tests, and twice daily questionnaires. During their administration the two drugs were practically indistinguishable in their effects. Both significantly reduced objective and subjective measures of insomnia, such as total wake time and sleep latency. On discontinuation the drugs differentially affected sleep, e.g., on the first post flurazepam night total sleep time was significantly more than baseline whereas on first post triazolam night, total sleep time was significantly less than baseline. There were no remarkable side or toxic effects with either drug.", "contents": "A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs. The effects of oral, bedtime triazolam 0.5 mg and flurazepam 30 mg, on the laboratory sleep of 12 insomniacs were compared in a double blind, crossover study. A 22 consecutive night schedule was used: Nts. 1--2 placebo; 3--6 first drug; 7--8 placebo; 9--14 no drugs; 15--16 placebo; 17--20 second drug; 21--22 placebo. In 6 Ss first drug was triazolam and second drug was flurazepam. In the other 6 Ss the drug order was reversed. Effects on sleep were assessed objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by physical exams, clinical lab tests, and twice daily questionnaires. During their administration the two drugs were practically indistinguishable in their effects. Both significantly reduced objective and subjective measures of insomnia, such as total wake time and sleep latency. On discontinuation the drugs differentially affected sleep, e.g., on the first post flurazepam night total sleep time was significantly more than baseline whereas on first post triazolam night, total sleep time was significantly less than baseline. There were no remarkable side or toxic effects with either drug."}
{"id": "PMID:8814", "title": "Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving long-term phenothiazine treatment.", "content": "Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug.", "contents": "Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving long-term phenothiazine treatment. Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug."}
{"id": "PMID:8815", "title": "Characteristics of pentobarbital discrimination in the gerbil: transfer and antagonism.", "content": "Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5-9.6 mg/kg) and metrazol (ED50:24.9-27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100-1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb, solely. Gerbils trained without a drug s-imulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2.", "contents": "Characteristics of pentobarbital discrimination in the gerbil: transfer and antagonism. Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED50 of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED50: 8.5-9.6 mg/kg) and metrazol (ED50:24.9-27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100-1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb, solely. Gerbils trained without a drug s-imulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2."}
{"id": "PMID:8818", "title": "Structure-activity relationships among desmethyl derivatives of neuroleptics and antidepressants for substrate specificty to indolethylamine N-methyltransferase from rabbit lung.", "content": "Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation.", "contents": "Structure-activity relationships among desmethyl derivatives of neuroleptics and antidepressants for substrate specificty to indolethylamine N-methyltransferase from rabbit lung. Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation."}
{"id": "PMID:8820", "title": "Effects of flurazepam (Dalmane) on anterior pituitary secretion.", "content": "Sleep stages and release patterns for growth hormone (GH), luteinizing hormone (LH) and prolactin were evaluated in two subjects during a three week period in which flurazepam 30 mg was administered nightly. Sleep stages were monitored throughout the placebo-baseline, drug and placebo-withdrawal conditions. Blood samples were obtained on nights three and four of baseline, after two and three weeks of drug administration and following extended drug withdrawal. In both subjects, flurazepam produced a marked suppression in stages 3 and 4 (slow wave) sleep which was maintained throughout the drug administration period. Following withdrawal, there was a slight increase in slow wave sleep above baseline levels. With all three hormones, no clear cut changes were observed in mean nightly output, pulse amplitude and pulse frequency from baseline to the drug and the withdrawal conditions. Thus, the decrease in slow wave sleep produced by administering flurazepam 30 mg was not accompanied by any clear cut changes in GH, LH or prolactin.", "contents": "Effects of flurazepam (Dalmane) on anterior pituitary secretion. Sleep stages and release patterns for growth hormone (GH), luteinizing hormone (LH) and prolactin were evaluated in two subjects during a three week period in which flurazepam 30 mg was administered nightly. Sleep stages were monitored throughout the placebo-baseline, drug and placebo-withdrawal conditions. Blood samples were obtained on nights three and four of baseline, after two and three weeks of drug administration and following extended drug withdrawal. In both subjects, flurazepam produced a marked suppression in stages 3 and 4 (slow wave) sleep which was maintained throughout the drug administration period. Following withdrawal, there was a slight increase in slow wave sleep above baseline levels. With all three hormones, no clear cut changes were observed in mean nightly output, pulse amplitude and pulse frequency from baseline to the drug and the withdrawal conditions. Thus, the decrease in slow wave sleep produced by administering flurazepam 30 mg was not accompanied by any clear cut changes in GH, LH or prolactin."}
{"id": "PMID:8821", "title": "Biochemical localization of gamma-glutamyl transpeptidase within cellular elements of the rat cerebral cortex.", "content": "The presence of the enzyme gamma-glutamyl transpeptidase was established in cellular elements of the rat cerebral cortex. Lowest enzyme activity was found in the total cerebral homogenate while approximately four-fold increased enzymatic activities were evident in capillary-enriched, glial-enriched and purified neuronal fractions.", "contents": "Biochemical localization of gamma-glutamyl transpeptidase within cellular elements of the rat cerebral cortex. The presence of the enzyme gamma-glutamyl transpeptidase was established in cellular elements of the rat cerebral cortex. Lowest enzyme activity was found in the total cerebral homogenate while approximately four-fold increased enzymatic activities were evident in capillary-enriched, glial-enriched and purified neuronal fractions."}
{"id": "PMID:8822", "title": "The acid--base status: a mathematical approach to its definition.", "content": "The respiratory and non-respiratory factors of acid--base status have been evaluated mathematically. New units of measurement for derangements of the acid--base balance are proposed.", "contents": "The acid--base status: a mathematical approach to its definition. The respiratory and non-respiratory factors of acid--base status have been evaluated mathematically. New units of measurement for derangements of the acid--base balance are proposed."}
{"id": "PMID:8823", "title": "pH, temperature, humidity and the dynamic force-area curve of dipalmitoyl lecithin.", "content": "Both high pH at 25 degrees C and humidity at 37 degrees C prevent DPL films from attaining zero surface tension, whereas humidity at 25 degrees C and high pH at 37 degrees C do not. At 37 degrees C DPL lowered surface tension to zero when spread from organic solvent or when absorbed from aqueous 0.15 M NaCl in the surface balance in which the surface film was exposed to the room air (dry film). Upon saturation of the atmosphere with water vapor in equilibrium with the aqueous phase at 37 degrees C in a closed chamber, DPL lost the ability to produce zero surface tension, and the gamma min of the DPL film increased from zero to 22 dyne/cm. Addition of DPL in chloroform to distilled water before dispersion by sonication did not prevent the effect of the humidity. However, when the chloroform solution of DPL was added to 0.15 M NaCl before sonication, the adsorbed film produced immediately a stable gamma min of zero in a saturated atmosphere, 37 degrees C. In the absence of chloroform, with DPL adsorbed from either distilled water or 0.15 M NaCl, the effect of humidity was reversed either by removing the chamber and returning the wet film to room air or by introducing small quantities of dispersing agents such as cholesteryl palmitate. However, whereas the effect of humidifying the air was reversible indefinitely, the effect of cholesteryl palmitate (zero surface tension, wet or dry film) was irreversible. This means that there are substances or conditions that can assist DPL films in maintaining zero surface tension when such films are exposed to humidity-saturated air at 37 degrees C.", "contents": "pH, temperature, humidity and the dynamic force-area curve of dipalmitoyl lecithin. Both high pH at 25 degrees C and humidity at 37 degrees C prevent DPL films from attaining zero surface tension, whereas humidity at 25 degrees C and high pH at 37 degrees C do not. At 37 degrees C DPL lowered surface tension to zero when spread from organic solvent or when absorbed from aqueous 0.15 M NaCl in the surface balance in which the surface film was exposed to the room air (dry film). Upon saturation of the atmosphere with water vapor in equilibrium with the aqueous phase at 37 degrees C in a closed chamber, DPL lost the ability to produce zero surface tension, and the gamma min of the DPL film increased from zero to 22 dyne/cm. Addition of DPL in chloroform to distilled water before dispersion by sonication did not prevent the effect of the humidity. However, when the chloroform solution of DPL was added to 0.15 M NaCl before sonication, the adsorbed film produced immediately a stable gamma min of zero in a saturated atmosphere, 37 degrees C. In the absence of chloroform, with DPL adsorbed from either distilled water or 0.15 M NaCl, the effect of humidity was reversed either by removing the chamber and returning the wet film to room air or by introducing small quantities of dispersing agents such as cholesteryl palmitate. However, whereas the effect of humidifying the air was reversible indefinitely, the effect of cholesteryl palmitate (zero surface tension, wet or dry film) was irreversible. This means that there are substances or conditions that can assist DPL films in maintaining zero surface tension when such films are exposed to humidity-saturated air at 37 degrees C."}
{"id": "PMID:8829", "title": "A micro-method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation and lipolysis in vitro in needle biopsies of human adipose tissue.", "content": "A method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation into adipose tissue in vitro in needle biopsy specimens of human fat has been developed. 20-150 mg of subcutaneous fat is incubated in an albumin buffer containing a physiological spectrum and concentration of fatty acids and glucose. Release of glycerol and fatty acids to the incubation medium and incorporation of labelled palmitic acid and labelled glucose into extracted adipose tissue lipids are determined simultaneously. The labelled fatty acids are found in the fatty acid part and the labelled glucose only in the glycerol part of extracted diglycerides and triglycerides. These glycerides are completely recovered and indicated FIAT and GLIAT values. Methodological errors for all vaiables are about 10%. All processes increase linearly with tissue weight and incubation time. FIAT and GLIAT increase linearly with increasing concentration of a physiological spectrum of fatty acids (=constant fractional incorporation). The method is simple, and several analyses from one subject can be performed on one day with a minimum of discomfort to the patient.", "contents": "A micro-method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation and lipolysis in vitro in needle biopsies of human adipose tissue. A method for determination of fatty acid (FIAT) and glucose (GLIAT) incorporation into adipose tissue in vitro in needle biopsy specimens of human fat has been developed. 20-150 mg of subcutaneous fat is incubated in an albumin buffer containing a physiological spectrum and concentration of fatty acids and glucose. Release of glycerol and fatty acids to the incubation medium and incorporation of labelled palmitic acid and labelled glucose into extracted adipose tissue lipids are determined simultaneously. The labelled fatty acids are found in the fatty acid part and the labelled glucose only in the glycerol part of extracted diglycerides and triglycerides. These glycerides are completely recovered and indicated FIAT and GLIAT values. Methodological errors for all vaiables are about 10%. All processes increase linearly with tissue weight and incubation time. FIAT and GLIAT increase linearly with increasing concentration of a physiological spectrum of fatty acids (=constant fractional incorporation). The method is simple, and several analyses from one subject can be performed on one day with a minimum of discomfort to the patient."}
{"id": "PMID:8830", "title": "Crohn's disease of the distal large bowel.", "content": "This study describes the clinical features and management of 80 patients with Crohn's disease affecting initially only the rectum with or without involvement of the sigmoid colon. Most patients were treated medically, and the various measures used are considered; the cumulative probability of completing five years under conservative management was 60% among survivors. The related mortality was very low and confined to patients treated surgically; with 655.24 patient-years of follow-up the number of observed deaths was lower than the number expected from all causes. Since this distribution of the disease is usually seen in older patients and carries a favourable prognosis, it it suggested that it should be considered as a well-defined variant of the condition.", "contents": "Crohn's disease of the distal large bowel. This study describes the clinical features and management of 80 patients with Crohn's disease affecting initially only the rectum with or without involvement of the sigmoid colon. Most patients were treated medically, and the various measures used are considered; the cumulative probability of completing five years under conservative management was 60% among survivors. The related mortality was very low and confined to patients treated surgically; with 655.24 patient-years of follow-up the number of observed deaths was lower than the number expected from all causes. Since this distribution of the disease is usually seen in older patients and carries a favourable prognosis, it it suggested that it should be considered as a well-defined variant of the condition."}
{"id": "PMID:8831", "title": "Immunogenetic analysis of H-2 mutations. IV. Mapping of and immune reactions to the H-2fa mutation.", "content": "H-2fa is a spontaneous mutation that occurred in an (A.CA X A)F1 female mouse and was later transferred on an A-strain background [congenic line A.CA (M506) or M506]. Skin grafts exchanged between M506 and A.CA strains are rejected within 4 weeks after grafting. Significant reaction is observed when these two strains are used as responders and stimulators in mixed lymphocyte culture or in a splenomegaly graft-versus-host assay. The mutant antigen induces strong cell-mediated lymphocytotoxicity. The mutation maps in the K end of the H-2 complex. The capacity of mutant antigens to induce relatively strong lymphocyte proliferation is explained by hypothesizing that the T-cell receptors reacting with K- or D-region products can more easily recognize subtle than drastic alloantigenic differences.", "contents": "Immunogenetic analysis of H-2 mutations. IV. Mapping of and immune reactions to the H-2fa mutation. H-2fa is a spontaneous mutation that occurred in an (A.CA X A)F1 female mouse and was later transferred on an A-strain background [congenic line A.CA (M506) or M506]. Skin grafts exchanged between M506 and A.CA strains are rejected within 4 weeks after grafting. Significant reaction is observed when these two strains are used as responders and stimulators in mixed lymphocyte culture or in a splenomegaly graft-versus-host assay. The mutant antigen induces strong cell-mediated lymphocytotoxicity. The mutation maps in the K end of the H-2 complex. The capacity of mutant antigens to induce relatively strong lymphocyte proliferation is explained by hypothesizing that the T-cell receptors reacting with K- or D-region products can more easily recognize subtle than drastic alloantigenic differences."}
{"id": "PMID:8832", "title": "Maternal immunocompetence. I. The graft-versus-host reactivity of lymphocytes from pregnant rats and the distribution pattern of 51Cr-labeled lymphocytes in pregnant mice.", "content": "Lymphocytes from the peripheral blood, spleen, or para-aortic lymph nodes of prrimigravida L rats carrying (L X BN) F1 (LBN) fetuses are fully capable of mounting graft-versus-host (GVH) reactions in LBN F1 recipients. The reactivity of lymphocytes from interstrain pregnant (L X BN) or intrastrain pregnant (L X L) rats, or from rats postpartum from these pregnancies, is equivalent to that of normal virgin females over a full dose-response curve, ruling out both specific and nonspecific effects of pregnancy on the intrinsic GVH competence of the maternal thymus-derived (T) lymphocyte. Attempts to block GVH reactivity with serum from pregnant rats were unsuccessful. In addition, when the distribution pattern of 51Cr-labeled syngeneic and semiallogeneic lymphocytes was studied in intact primigravida mice, there was no difference between interstrain and intrastrain pregnant mice, and there was no evidence of immunologically specific 'trapping' in the para-aortic lymph nodes draining the interstrain pregnant uterus.", "contents": "Maternal immunocompetence. I. The graft-versus-host reactivity of lymphocytes from pregnant rats and the distribution pattern of 51Cr-labeled lymphocytes in pregnant mice. Lymphocytes from the peripheral blood, spleen, or para-aortic lymph nodes of prrimigravida L rats carrying (L X BN) F1 (LBN) fetuses are fully capable of mounting graft-versus-host (GVH) reactions in LBN F1 recipients. The reactivity of lymphocytes from interstrain pregnant (L X BN) or intrastrain pregnant (L X L) rats, or from rats postpartum from these pregnancies, is equivalent to that of normal virgin females over a full dose-response curve, ruling out both specific and nonspecific effects of pregnancy on the intrinsic GVH competence of the maternal thymus-derived (T) lymphocyte. Attempts to block GVH reactivity with serum from pregnant rats were unsuccessful. In addition, when the distribution pattern of 51Cr-labeled syngeneic and semiallogeneic lymphocytes was studied in intact primigravida mice, there was no difference between interstrain and intrastrain pregnant mice, and there was no evidence of immunologically specific 'trapping' in the para-aortic lymph nodes draining the interstrain pregnant uterus."}
{"id": "PMID:8833", "title": "Distribution of benorylate in plasma, synovial fluid and tissue in rheumatoid arthritis.", "content": "Six patients, not previously treated, with classical seropositive rheumatoid arthritis and highly active synovitis of one or both knee joints were treated with 4 g of 40% benorylate suspension twice daily for a period of 9--14 days prior to synovectomy. Blood samples were taken at scheduled times during administration of the drug. At operation, synovial fluid and tissue samples were taken and their salicylate, paracetamol and benorylate content measured. Plasma levels of salicylate and paracetamol were, in general, significantly higher than the concentration of these metabolites in the synovial fluid. Benorylate was found in the synovial tissues concentrated especially in the highly inflamed synovial villi. It is probable that benorylate and its metabolites penetrate the synovia but further studies are needed to determine if the metabolites are concentrated in the different synovial cell layers in the same way as benorylate itself. It is possible that part of the clinical effect of benorylate is due to its presence in the synovial tissue and that it has a direct effect in vivo on the synovial membrane. It is also possible that the pharmacokinetic properties of benorylate permit it to enter cell layers inaccessible to its metabolites.", "contents": "Distribution of benorylate in plasma, synovial fluid and tissue in rheumatoid arthritis. Six patients, not previously treated, with classical seropositive rheumatoid arthritis and highly active synovitis of one or both knee joints were treated with 4 g of 40% benorylate suspension twice daily for a period of 9--14 days prior to synovectomy. Blood samples were taken at scheduled times during administration of the drug. At operation, synovial fluid and tissue samples were taken and their salicylate, paracetamol and benorylate content measured. Plasma levels of salicylate and paracetamol were, in general, significantly higher than the concentration of these metabolites in the synovial fluid. Benorylate was found in the synovial tissues concentrated especially in the highly inflamed synovial villi. It is probable that benorylate and its metabolites penetrate the synovia but further studies are needed to determine if the metabolites are concentrated in the different synovial cell layers in the same way as benorylate itself. It is possible that part of the clinical effect of benorylate is due to its presence in the synovial tissue and that it has a direct effect in vivo on the synovial membrane. It is also possible that the pharmacokinetic properties of benorylate permit it to enter cell layers inaccessible to its metabolites."}
{"id": "PMID:8834", "title": "The passage of benorylate into the synovial fluid and tissue of rheumatoid patients.", "content": "After a preliminary wash-out period of 3-7 days during which no anti-inflammatory drugs were given, 11 female patients with classical or definite rheumatoid arthritis were given 8 g of benorylate as the 40% suspension 3-7 days prior to synovectomy of the knee. Samples of synovial tissue and fluid from the affected knee were assayed for their content of benorylate, salicylate and paracetamol in an attempt to relat these concentrations to the length of medication and the severity of the disease process as measured clinically, by X-ray, by open inspection at operation and by histology of the synovial tissue. The esterase activity of the blood and synovial fluid was also measured by the capacity to hydrolyse benorylate used as substrate.", "contents": "The passage of benorylate into the synovial fluid and tissue of rheumatoid patients. After a preliminary wash-out period of 3-7 days during which no anti-inflammatory drugs were given, 11 female patients with classical or definite rheumatoid arthritis were given 8 g of benorylate as the 40% suspension 3-7 days prior to synovectomy of the knee. Samples of synovial tissue and fluid from the affected knee were assayed for their content of benorylate, salicylate and paracetamol in an attempt to relat these concentrations to the length of medication and the severity of the disease process as measured clinically, by X-ray, by open inspection at operation and by histology of the synovial tissue. The esterase activity of the blood and synovial fluid was also measured by the capacity to hydrolyse benorylate used as substrate."}
{"id": "PMID:8835", "title": "A long-term study of benorylate in patients with rheumatoid arthritis.", "content": "The analgesic and anti-inflammatory efficacy and adverse effects of benorylate were studied over a period of 6 months in 33 patients suffering from definite or classical rheumatoid arthritis. The average dose used was 6 g daily and examinations were made before treatment and at regular intervals during treatment to assess the clinical status of the patient, tolerance to the drug and any effect on blood, liver or renal function. Benorylate had a satisfactory effect in 28 patients. Additional treatment was requried in 3 cases and treatment discontinued in 2 cases. Distinct improvement of grip strength, morning stiffness and E.S.R. in 25 cases indicates the anti-inflammatory efficacy of benorylate. There were no signs of toxicity to bone marrow, liver or kidney. Severe side effects such as stomch ulcers, gastrointestinal bleeding and severe allergic complications were not observed. Side effects such as constipation and tinnitus that occurred at the beginning of treatment were mainly of a a passing nature and disappeared without a need to change therapy. Benorylate is suitable for the treatment of recent rheumatoid arthritis of a low to moderate activity as well as for long-term treatment.", "contents": "A long-term study of benorylate in patients with rheumatoid arthritis. The analgesic and anti-inflammatory efficacy and adverse effects of benorylate were studied over a period of 6 months in 33 patients suffering from definite or classical rheumatoid arthritis. The average dose used was 6 g daily and examinations were made before treatment and at regular intervals during treatment to assess the clinical status of the patient, tolerance to the drug and any effect on blood, liver or renal function. Benorylate had a satisfactory effect in 28 patients. Additional treatment was requried in 3 cases and treatment discontinued in 2 cases. Distinct improvement of grip strength, morning stiffness and E.S.R. in 25 cases indicates the anti-inflammatory efficacy of benorylate. There were no signs of toxicity to bone marrow, liver or kidney. Severe side effects such as stomch ulcers, gastrointestinal bleeding and severe allergic complications were not observed. Side effects such as constipation and tinnitus that occurred at the beginning of treatment were mainly of a a passing nature and disappeared without a need to change therapy. Benorylate is suitable for the treatment of recent rheumatoid arthritis of a low to moderate activity as well as for long-term treatment."}
{"id": "PMID:8836", "title": "A double-blind study of the analgesic action of benorylate suspension in osteoarthritis of the hip and knee.", "content": "This study compared benorylate suspension and placebo in a double-blind randomised cross-over design to investigate their analgesic effect in osteoarthritis of the hip and the knee. Benorylate and placebo were each given for 7 days. Assessment of efficacy and tolerance was carried out on the 7th day of each period. The results were subjected to sequential analysis and the analgesic effect of benorylate suspension was significantly demonstrated after 8 case reports. Mild digestive side effects appeared in 30% of patients. In addition, benorylate suspension was well tolerated in an open trial carried on for 30 to 90 days in 7 patients.", "contents": "A double-blind study of the analgesic action of benorylate suspension in osteoarthritis of the hip and knee. This study compared benorylate suspension and placebo in a double-blind randomised cross-over design to investigate their analgesic effect in osteoarthritis of the hip and the knee. Benorylate and placebo were each given for 7 days. Assessment of efficacy and tolerance was carried out on the 7th day of each period. The results were subjected to sequential analysis and the analgesic effect of benorylate suspension was significantly demonstrated after 8 case reports. Mild digestive side effects appeared in 30% of patients. In addition, benorylate suspension was well tolerated in an open trial carried on for 30 to 90 days in 7 patients."}
{"id": "PMID:8837", "title": "Benorylate: a report on 2 years' experience of its use in rheumatoid arthritis and other chronic rheumatic diseases.", "content": "52 outpatients with rheumatoid arthritis or osteoarthritis were given benorylate (as the 40% suspension) in doses of up to 8 g daily. Peroids of medication were varied but some patients were given the drug for nearly 2 years. Assessments of clinical progress were made at regular intervals by recording both subjective and objective measurements including duration of morning stiffness, grip strength, joint size. Laboratory investigations include renal function tests, liver function tests, blood picture and occult blood. No serious side effect, attributable to benorylate was reported and it was concluded that the drug is satisfactory for the long term treatment of rheumatic diseases.", "contents": "Benorylate: a report on 2 years' experience of its use in rheumatoid arthritis and other chronic rheumatic diseases. 52 outpatients with rheumatoid arthritis or osteoarthritis were given benorylate (as the 40% suspension) in doses of up to 8 g daily. Peroids of medication were varied but some patients were given the drug for nearly 2 years. Assessments of clinical progress were made at regular intervals by recording both subjective and objective measurements including duration of morning stiffness, grip strength, joint size. Laboratory investigations include renal function tests, liver function tests, blood picture and occult blood. No serious side effect, attributable to benorylate was reported and it was concluded that the drug is satisfactory for the long term treatment of rheumatic diseases."}
{"id": "PMID:8838", "title": "Clinical study of a new anti-inflammatory and analgesic compound, benorylate, in rheumatic disorders.", "content": "Benorylate is obtained by esterification of acetylsalicylic acid and N-acetyl p-aminophenol (4-acetamidophenyl 2-acetoxybenzoate). Experimentally, this new product has been shown to be a good analgesic and anti-inflammatory agent. A clinical trial was carried out in order to study the efficacy, side effects and tolerance of this new product. In a group of 49 hospitalised patients aged from 20 to 70 years who were treated with this new product, 15 had ankylosing spondylitis, 11 had chronic progressive rheumatoid arthritis, 4 had Reiter's syndrome, 4 had psoriatic arthropathy, 8 had osteoarthrosis of the hip and 7 had various forms of rheumatism. The drug was administered orally in suspension form, initially three times per day, then twice, the total daily doses being 15 ml (6 g) or 20 ml (8 g). Treatment was regarded as effective in 62% of the cases, and of these 62%, 46% good and very good results were obtained. In 88% of the patients, tolerance was satisfactory and of these, it was excellent in 80%. Only in 2 cases did treatment have to be discontinued on account of side effects. From the biological point of view, uricaemia was significantly reduced in 7 patients, and in 6 patients uricuria increased. With regard to the level of salicylate in the blood assays showed that it is the same for 6 g benorylate and for 4 g aspirin. Benorylate has been shown to be an effective treatment for both inflammatory and degenerative rheumatic disorders. The results of its use can be compared with those obtained by acetylsalicylic acid, but is better tolerated. In addition, in chronic disorders it is better to have to take the product only twice per day.", "contents": "Clinical study of a new anti-inflammatory and analgesic compound, benorylate, in rheumatic disorders. Benorylate is obtained by esterification of acetylsalicylic acid and N-acetyl p-aminophenol (4-acetamidophenyl 2-acetoxybenzoate). Experimentally, this new product has been shown to be a good analgesic and anti-inflammatory agent. A clinical trial was carried out in order to study the efficacy, side effects and tolerance of this new product. In a group of 49 hospitalised patients aged from 20 to 70 years who were treated with this new product, 15 had ankylosing spondylitis, 11 had chronic progressive rheumatoid arthritis, 4 had Reiter's syndrome, 4 had psoriatic arthropathy, 8 had osteoarthrosis of the hip and 7 had various forms of rheumatism. The drug was administered orally in suspension form, initially three times per day, then twice, the total daily doses being 15 ml (6 g) or 20 ml (8 g). Treatment was regarded as effective in 62% of the cases, and of these 62%, 46% good and very good results were obtained. In 88% of the patients, tolerance was satisfactory and of these, it was excellent in 80%. Only in 2 cases did treatment have to be discontinued on account of side effects. From the biological point of view, uricaemia was significantly reduced in 7 patients, and in 6 patients uricuria increased. With regard to the level of salicylate in the blood assays showed that it is the same for 6 g benorylate and for 4 g aspirin. Benorylate has been shown to be an effective treatment for both inflammatory and degenerative rheumatic disorders. The results of its use can be compared with those obtained by acetylsalicylic acid, but is better tolerated. In addition, in chronic disorders it is better to have to take the product only twice per day."}
{"id": "PMID:8840", "title": "A review of benorylate - a new antirheumatic drug.", "content": "Benorylate (Benoral, Benortan) is the esterification product of paracetamol and acetylsalicylic acid. It has anti-inflammatory, analgesic and antipyretic properties. Benorylate is probably absorbed as the intact molecule which accounts for its good gastric tolerance. After absorption, benorylate is hydrolysed into its components, salicylate and paracetamol, which then follows the usual routes of metabolism. Benorylate per se is also found in inflamed tissue and several studies, both in vivo and in vitro, have shown that it probably has an anti-inflammatory action of its own. Pharmacokinetic studies have shown that a twice daily administration of benorylate should be sufficient for a therapeutic effect and this has been confirmed by its use in patients. Clinical studies have compared benorylate with aspirin, indomethacin, ibuprofen and phenylbutazone and have shown its value in rheumatoid arthritis, osteoarthrosis and other musculoskeletal conditions. The overall tolerance is excellent. Some minor gastric disturbances are reported from time to time, but these are less than with comparable doses of aspirin. Studies measuring occult blood loss in the stools have shown that this is not a significant problem with benorylate and that the majority of patients lose no more blood than the controls.", "contents": "A review of benorylate - a new antirheumatic drug. Benorylate (Benoral, Benortan) is the esterification product of paracetamol and acetylsalicylic acid. It has anti-inflammatory, analgesic and antipyretic properties. Benorylate is probably absorbed as the intact molecule which accounts for its good gastric tolerance. After absorption, benorylate is hydrolysed into its components, salicylate and paracetamol, which then follows the usual routes of metabolism. Benorylate per se is also found in inflamed tissue and several studies, both in vivo and in vitro, have shown that it probably has an anti-inflammatory action of its own. Pharmacokinetic studies have shown that a twice daily administration of benorylate should be sufficient for a therapeutic effect and this has been confirmed by its use in patients. Clinical studies have compared benorylate with aspirin, indomethacin, ibuprofen and phenylbutazone and have shown its value in rheumatoid arthritis, osteoarthrosis and other musculoskeletal conditions. The overall tolerance is excellent. Some minor gastric disturbances are reported from time to time, but these are less than with comparable doses of aspirin. Studies measuring occult blood loss in the stools have shown that this is not a significant problem with benorylate and that the majority of patients lose no more blood than the controls."}
{"id": "PMID:8841", "title": "Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis.", "content": "Twenty patients with definite or classical rheumatoid arthritis and chronic knee effusions were each given an oral dose of 4 g benorylate as the 40% suspension. Synovial fluid and plasma samples were obtained up to 9 hours after drug administration and assayed for their salicylate and benorylate content. A mean peak benorylate plasma level of 2.18 +/- 0.19 mug/ml occurred 30 min after drug administration but declined rapidly and benorylate was virtually undetectable in the plasma 90 min later. The mean peak benorylate synovial fluid level of 0.74 +/- 0.21 mug/ml occurred 3 hours after drug administration but the concentration remained steady for at least a further 9 hours. A mean peak plasma salicylate level of 119 +/- 14.2 mug/ml and mean peak synovial fluid salicylate level of 78 +/- 13.6 mug/ml occurred 3 hours after benorylate administration. Both levels declined slowly over some hours. This study shows that benorylate per se readily enters the synovial fluid in patients with rheumatoid arthritis and continues to accumulate there even when undetectable in the plasma. It is possible that the lipophilic nature of the benorylate molecule facilitates its uptake by the inflamed synovial tissue.", "contents": "Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis. Twenty patients with definite or classical rheumatoid arthritis and chronic knee effusions were each given an oral dose of 4 g benorylate as the 40% suspension. Synovial fluid and plasma samples were obtained up to 9 hours after drug administration and assayed for their salicylate and benorylate content. A mean peak benorylate plasma level of 2.18 +/- 0.19 mug/ml occurred 30 min after drug administration but declined rapidly and benorylate was virtually undetectable in the plasma 90 min later. The mean peak benorylate synovial fluid level of 0.74 +/- 0.21 mug/ml occurred 3 hours after drug administration but the concentration remained steady for at least a further 9 hours. A mean peak plasma salicylate level of 119 +/- 14.2 mug/ml and mean peak synovial fluid salicylate level of 78 +/- 13.6 mug/ml occurred 3 hours after benorylate administration. Both levels declined slowly over some hours. This study shows that benorylate per se readily enters the synovial fluid in patients with rheumatoid arthritis and continues to accumulate there even when undetectable in the plasma. It is possible that the lipophilic nature of the benorylate molecule facilitates its uptake by the inflamed synovial tissue."}
{"id": "PMID:8842", "title": "Muscle crossbridges: absence of direct effect of calcium on movement away from the thick filaments.", "content": "Fluorescence depolarization experiments show that the rotary mobility of myosin heads is hindered by the assembly of the thick filament. Calcium, with or without magnesium adenosine triphosphate, dose not alter this hindrance in synthetic filaments. This implies that calcium does not directly move the crossbridges toward thin filaments on activation of muscle.", "contents": "Muscle crossbridges: absence of direct effect of calcium on movement away from the thick filaments. Fluorescence depolarization experiments show that the rotary mobility of myosin heads is hindered by the assembly of the thick filament. Calcium, with or without magnesium adenosine triphosphate, dose not alter this hindrance in synthetic filaments. This implies that calcium does not directly move the crossbridges toward thin filaments on activation of muscle."}
{"id": "PMID:8843", "title": "[Identification of organic substances by means of spectral methods in forensic toxicology. I. Infrared spectroscopy].", "content": "In the introduction the author gives an outline of the principles of infrared spectroscopy and possibilities of its use for the identification of organic substances. On examples from practice he demonstrates the use of infrared spectroscopy in forensic toxicology. He desribes methods for the isolation of substances from biological material and methods of their purification. The applied methods are used for common toxicological analyses. Attention is drawn to the possibility of comprehensive identification of the structure or a comound based on an analysis of the infrared spetrum and analysis of a mixture of two substances is is described. Infrared spectroscopy is a very suitable method for the unequivocal identification even of very small amounts of substances obtained from material (biological and corpora delicti) in intoxications with organic substances, such a as drugs, pesticides, etc.", "contents": "[Identification of organic substances by means of spectral methods in forensic toxicology. I. Infrared spectroscopy]. In the introduction the author gives an outline of the principles of infrared spectroscopy and possibilities of its use for the identification of organic substances. On examples from practice he demonstrates the use of infrared spectroscopy in forensic toxicology. He desribes methods for the isolation of substances from biological material and methods of their purification. The applied methods are used for common toxicological analyses. Attention is drawn to the possibility of comprehensive identification of the structure or a comound based on an analysis of the infrared spetrum and analysis of a mixture of two substances is is described. Infrared spectroscopy is a very suitable method for the unequivocal identification even of very small amounts of substances obtained from material (biological and corpora delicti) in intoxications with organic substances, such a as drugs, pesticides, etc."}
{"id": "PMID:8844", "title": "Recent advances in experimental leprosy.", "content": "Within the last 15 years we have learned to identify Mycobacterium leprae, determine its viability, screen the efficacy of antileprosy drugs, and monitor the bacilli for drug sensitivity. We have evidence that subclinical infections occur frequently among contacts of patients with leprosy and that the different manifestations of leprosy reflect differences in resistance to M leprae. We are developing hypotheses about the mechanism of these differences. We have experimentally transmitted lepromatous leprosy to normal armadillos, and from these we can obtain amounts of leprosy bacilli which fully substitute for harvests from in vitro cultures. Furthermore, if susceptibility of armadillos can be determined without infecting them and if we can breed them under controlled conditions, we would have an animal model for investigating fundamental and applied areas of leprosy which otherwise are intractable. How much our knowledge has advanced is illustrated by a project of the World Health Organization which calls for the preparation of pure, specific antigens from the now available abundance of leprosy bacilli, which might become valuable as diagnostic and epidemiologic tools and as immunoprophylactic and even immunotherapeutic weapons.", "contents": "Recent advances in experimental leprosy. Within the last 15 years we have learned to identify Mycobacterium leprae, determine its viability, screen the efficacy of antileprosy drugs, and monitor the bacilli for drug sensitivity. We have evidence that subclinical infections occur frequently among contacts of patients with leprosy and that the different manifestations of leprosy reflect differences in resistance to M leprae. We are developing hypotheses about the mechanism of these differences. We have experimentally transmitted lepromatous leprosy to normal armadillos, and from these we can obtain amounts of leprosy bacilli which fully substitute for harvests from in vitro cultures. Furthermore, if susceptibility of armadillos can be determined without infecting them and if we can breed them under controlled conditions, we would have an animal model for investigating fundamental and applied areas of leprosy which otherwise are intractable. How much our knowledge has advanced is illustrated by a project of the World Health Organization which calls for the preparation of pure, specific antigens from the now available abundance of leprosy bacilli, which might become valuable as diagnostic and epidemiologic tools and as immunoprophylactic and even immunotherapeutic weapons."}
{"id": "PMID:8845", "title": "The survival of carp (Cyprinus carpio) outside water.", "content": "The possible use of the swimbladder of carp as auxiliary respiratory organ when the animals are exposed to air has been studied. After exposure to air, blood pH and pO2 and mean swimbladder O2 concentration decrease and blood pCO2 increases in normal animals. Exposure to air after ligation of the pneumatic ducts results in increases in blood pH and pCO2 and decreases in blood pO2 and swimbladder carbon dioxide concentration. Possible reasons for these observations are discussed.", "contents": "The survival of carp (Cyprinus carpio) outside water. The possible use of the swimbladder of carp as auxiliary respiratory organ when the animals are exposed to air has been studied. After exposure to air, blood pH and pO2 and mean swimbladder O2 concentration decrease and blood pCO2 increases in normal animals. Exposure to air after ligation of the pneumatic ducts results in increases in blood pH and pCO2 and decreases in blood pO2 and swimbladder carbon dioxide concentration. Possible reasons for these observations are discussed."}
{"id": "PMID:8849", "title": "The effects of mechanical preparation and acidification of the colon on the healing of colonic anastomoses.", "content": "The results of clinical studies have suggested that inadequate preoperative mechanical preparation of the colon is a significant factor in the pathogenesis of disruption of colonic and colorectal anastomoses. A possible explanation for the adverse effect of poor mechanical preparation is that ammonia released from feces has a cytotoxic effect on the healing anastomosis. It has been suggested that acidification of the colonic lumen prevents the release of fecal ammonia and protects the anastomoses. The effects of mechanical preparation of the colon and colonic acidification were studied in anastomoses in the left colon of rats. Colonic acidification was produced by the oral administration of a synthetic disaccharide lactulose solution. Mechanical preparation resulted in a significant increase in the bursting wall tension in anastomoses on the seventh postoperative day. The oral administration of lactulose resulted in a reduction in the colonic mucosal pH, but this was not accompanied by improved healing of anastomoses, as judged by measurements of colonic bursting pressure, bursting wall tension and total challagen content. Mechanical preparation of the colon is an important factor in the safety of colonic anastomosis. However, the results do not suggest that acidification of the colonic lumen significantly improves the quality of colonic healing.", "contents": "The effects of mechanical preparation and acidification of the colon on the healing of colonic anastomoses. The results of clinical studies have suggested that inadequate preoperative mechanical preparation of the colon is a significant factor in the pathogenesis of disruption of colonic and colorectal anastomoses. A possible explanation for the adverse effect of poor mechanical preparation is that ammonia released from feces has a cytotoxic effect on the healing anastomosis. It has been suggested that acidification of the colonic lumen prevents the release of fecal ammonia and protects the anastomoses. The effects of mechanical preparation of the colon and colonic acidification were studied in anastomoses in the left colon of rats. Colonic acidification was produced by the oral administration of a synthetic disaccharide lactulose solution. Mechanical preparation resulted in a significant increase in the bursting wall tension in anastomoses on the seventh postoperative day. The oral administration of lactulose resulted in a reduction in the colonic mucosal pH, but this was not accompanied by improved healing of anastomoses, as judged by measurements of colonic bursting pressure, bursting wall tension and total challagen content. Mechanical preparation of the colon is an important factor in the safety of colonic anastomosis. However, the results do not suggest that acidification of the colonic lumen significantly improves the quality of colonic healing."}
{"id": "PMID:8858", "title": "Higher activity of oxidative drug demethylation in the liver microsomes from dystrophic mouse.", "content": "The activities of NADPH-dependent oxidative demethylation of aminopyrine and other methyl compounds in the liver microsomes from dystrophic mice were found to be about 30% higher than those of the normal mice. Consumption of reduced pyridine nucleotides during the demethylation reactions was also significantly larger in the dystrophic mouse system than in the normal mouse system. The synergistic effect of further addition of NADH on the oxidative demethylation in the reaction system with NADPH, however, was not significant in either the normal or the dystrophic mouse system. The activities of NADPH-cytochrome c reductase and lipid peroxidation were also higher by about 30% in the dystrophic mouse than in the normal mouse, but the contents of cytochrome P-450 and phospholipids in the liver microsomes from normal and dystrophic mice were not appreciably different. The results suggest the possibility that the progressive muscular dystrophy may involve abnormal features in not only muscle but also liver and other tissues.", "contents": "Higher activity of oxidative drug demethylation in the liver microsomes from dystrophic mouse. The activities of NADPH-dependent oxidative demethylation of aminopyrine and other methyl compounds in the liver microsomes from dystrophic mice were found to be about 30% higher than those of the normal mice. Consumption of reduced pyridine nucleotides during the demethylation reactions was also significantly larger in the dystrophic mouse system than in the normal mouse system. The synergistic effect of further addition of NADH on the oxidative demethylation in the reaction system with NADPH, however, was not significant in either the normal or the dystrophic mouse system. The activities of NADPH-cytochrome c reductase and lipid peroxidation were also higher by about 30% in the dystrophic mouse than in the normal mouse, but the contents of cytochrome P-450 and phospholipids in the liver microsomes from normal and dystrophic mice were not appreciably different. The results suggest the possibility that the progressive muscular dystrophy may involve abnormal features in not only muscle but also liver and other tissues."}
{"id": "PMID:8859", "title": "Non-adrenergic inhibition of the electrical activity of the antrum muscle fibers of the guinea-pig stomach.", "content": "The changes in the electrical activity of the antrum muscle fibers of the guinea pig stomach caused by ATP and its related compounds were compared with those caused by catecholamines. The antrum preparation exhibited spontaneous electrical activity and this was suppressed or inhibited by treatment with catecholamines (adrenaline, noradrenaline and isoprenaline). The inhibitory actions of catecholamines were observed in the presence of tetrodotoxin or alpha-blockers (phentolamine or phenoxybenzamine) while the effects were antagonized by beta-blockers (propranolol or DCI). At higher concentrations than that of catecholamines, ATP or related nucleotides also produced the inhibitory effect on the spike activity and the generation of slow waves. The inhibitory actions of ATP and related substances were still observed in the presence of alpha- or beta-adrenergic blockers. Furthermore, the inhibition was present after treatment with tetrodotoxin. From these results, it is concluded that the inhibitory action of ATP and related compounds is due to a direct action on the antrum muscle and is not mediated via alpha- or beta-adrenoceptors.", "contents": "Non-adrenergic inhibition of the electrical activity of the antrum muscle fibers of the guinea-pig stomach. The changes in the electrical activity of the antrum muscle fibers of the guinea pig stomach caused by ATP and its related compounds were compared with those caused by catecholamines. The antrum preparation exhibited spontaneous electrical activity and this was suppressed or inhibited by treatment with catecholamines (adrenaline, noradrenaline and isoprenaline). The inhibitory actions of catecholamines were observed in the presence of tetrodotoxin or alpha-blockers (phentolamine or phenoxybenzamine) while the effects were antagonized by beta-blockers (propranolol or DCI). At higher concentrations than that of catecholamines, ATP or related nucleotides also produced the inhibitory effect on the spike activity and the generation of slow waves. The inhibitory actions of ATP and related substances were still observed in the presence of alpha- or beta-adrenergic blockers. Furthermore, the inhibition was present after treatment with tetrodotoxin. From these results, it is concluded that the inhibitory action of ATP and related compounds is due to a direct action on the antrum muscle and is not mediated via alpha- or beta-adrenoceptors."}
{"id": "PMID:8860", "title": "pH of amoebic liver pus.", "content": "Amoebic liver pus has an acidic pH. Hence the pleural aspirate from an amoebic empyema due to rupture of an amoebic liver abscess has an acidic pH. In contrast, the pH of pleural aspirates from effusions and empyema of non-amoebic aetiology were noted to have an alkaline pH. The clinical significance of these observations is discussed.", "contents": "pH of amoebic liver pus. Amoebic liver pus has an acidic pH. Hence the pleural aspirate from an amoebic empyema due to rupture of an amoebic liver abscess has an acidic pH. In contrast, the pH of pleural aspirates from effusions and empyema of non-amoebic aetiology were noted to have an alkaline pH. The clinical significance of these observations is discussed."}
{"id": "PMID:8862", "title": "The differential diagnosis of bronchial asthma in children.", "content": "Bronchial asthma in children is not uncommon in the tropics. Conditions simulating this disease in the tropics have been discussed with a view to arriving at a diagnosis without sophisticated investigations.", "contents": "The differential diagnosis of bronchial asthma in children. Bronchial asthma in children is not uncommon in the tropics. Conditions simulating this disease in the tropics have been discussed with a view to arriving at a diagnosis without sophisticated investigations."}
{"id": "PMID:8864", "title": "[Intermediate metabolism and respiratory function in peritonitis].", "content": "During observations of 26 patients and in acute and chronic experiments on 31 dogs under conditions of peritonitis the author studied neurohumoral relations and the effect of hydrocortisone on the respiratory function. A conclusion is made on the vital importance of the consistent associated corrective neurohumoral therapy with cholinomimetics and corticosteroids in peritonitis.", "contents": "[Intermediate metabolism and respiratory function in peritonitis]. During observations of 26 patients and in acute and chronic experiments on 31 dogs under conditions of peritonitis the author studied neurohumoral relations and the effect of hydrocortisone on the respiratory function. A conclusion is made on the vital importance of the consistent associated corrective neurohumoral therapy with cholinomimetics and corticosteroids in peritonitis."}
{"id": "PMID:8863", "title": "[Study of acid phosphatase II from Pichia guilliermondii yeasts].", "content": "Acid phosphatase II (AP II) was isolated from the cell-free extract of Pichia guilliermondii Wickerham ATCC 9058 and partially purified. The enzyme is a non-specific phosphomonoesterase. It hydrolyzes p-nitrohenyl-phophate (NPP), beta-glycerophosphate, glucose-6-phosphate, guanosine-5'-monophosphate, adenosine-5'-monophosphate, cytidine-5'-monophosphate, uridine-5'-monophosphate, alpha-naphtylphosphate, FMN. The order of the substrates corresponds to the degree of their hydrolysis decrease. The Michaelis constant of the enzyme was 1.4-10-3 M for NPP as a substrate, pH optimum was 5.5 and temperature optimum-40C. AP II was strongly inhibited by MoO4-2, F-, inorganic phosphate, Cu2+ and Be2+. The activity of the enzyme in the yeast cells does not change noticeably during growth on media with low and high iron content.", "contents": "[Study of acid phosphatase II from Pichia guilliermondii yeasts]. Acid phosphatase II (AP II) was isolated from the cell-free extract of Pichia guilliermondii Wickerham ATCC 9058 and partially purified. The enzyme is a non-specific phosphomonoesterase. It hydrolyzes p-nitrohenyl-phophate (NPP), beta-glycerophosphate, glucose-6-phosphate, guanosine-5'-monophosphate, adenosine-5'-monophosphate, cytidine-5'-monophosphate, uridine-5'-monophosphate, alpha-naphtylphosphate, FMN. The order of the substrates corresponds to the degree of their hydrolysis decrease. The Michaelis constant of the enzyme was 1.4-10-3 M for NPP as a substrate, pH optimum was 5.5 and temperature optimum-40C. AP II was strongly inhibited by MoO4-2, F-, inorganic phosphate, Cu2+ and Be2+. The activity of the enzyme in the yeast cells does not change noticeably during growth on media with low and high iron content."}
{"id": "PMID:8867", "title": "[Effect of physical and chemical factors on Pasteurella multocida bacteriophages].", "content": "Studied was the effect of some physical factors (temperature, pH of various values) and some chemical ones (urea, sodium citrate, sarcolysin, methylene blue, acridine orange, pyronin, crystal violet, potassium permanganate, fuchsin, tetracycline and tetraolean) on phages specifically lysing Pasteurella multocida strains, having the following signature: 3, 4, 6, 22, 32, 115, 967, 1075, and C-2. All investigated phages showed signs of inactivation at 48 degrees C with a further linear dependence, and at 65 degrees C up to 99.99 per cent of them were inactivated. With phages of group III inactivation discontinued between 50 and 60 degrees C, at 65 degrees C it being equal to that observed with I and II group phages. It was found that a broth medium of pH 7.5 was the optimum one for P. multocida phages. With altered pH values lowest percentage of survived phage particles showed I group phages, while those of II and III group proved more stable. So far as the chemical factors were concerned it was established that with the exception of pyronin and potassium permanganate which inactivated the P. multocida phages from 90 to 100 per cent, all other agents produced full inactivation (100 per cent). However urea did not inactivate I group phages, both it and sodium citrate inactivated partially II and III group phages. The variations established with the phages in terms of their physical and chemical behaviour may serve as subsidiary signs bearing upon their classification.", "contents": "[Effect of physical and chemical factors on Pasteurella multocida bacteriophages]. Studied was the effect of some physical factors (temperature, pH of various values) and some chemical ones (urea, sodium citrate, sarcolysin, methylene blue, acridine orange, pyronin, crystal violet, potassium permanganate, fuchsin, tetracycline and tetraolean) on phages specifically lysing Pasteurella multocida strains, having the following signature: 3, 4, 6, 22, 32, 115, 967, 1075, and C-2. All investigated phages showed signs of inactivation at 48 degrees C with a further linear dependence, and at 65 degrees C up to 99.99 per cent of them were inactivated. With phages of group III inactivation discontinued between 50 and 60 degrees C, at 65 degrees C it being equal to that observed with I and II group phages. It was found that a broth medium of pH 7.5 was the optimum one for P. multocida phages. With altered pH values lowest percentage of survived phage particles showed I group phages, while those of II and III group proved more stable. So far as the chemical factors were concerned it was established that with the exception of pyronin and potassium permanganate which inactivated the P. multocida phages from 90 to 100 per cent, all other agents produced full inactivation (100 per cent). However urea did not inactivate I group phages, both it and sodium citrate inactivated partially II and III group phages. The variations established with the phages in terms of their physical and chemical behaviour may serve as subsidiary signs bearing upon their classification."}
{"id": "PMID:8871", "title": "Studies on new process procedures in plasma fractionation on an industrial scale. I. Determination of the pH value of ethanol containing protein solutions at low temperatures.", "content": "A suitable combined pH electode is evaluated which provides reproducible readings under the extreme conditions of the cold ethanol plasma fractionation procedure. Adequately reproducible correlations are found between the pH measurements in protein solutions with an ethanol content of up to 40% at temperatures as low as -8 degrees C and the determination in diluted samples at room temperature using the standard procedure.", "contents": "Studies on new process procedures in plasma fractionation on an industrial scale. I. Determination of the pH value of ethanol containing protein solutions at low temperatures. A suitable combined pH electode is evaluated which provides reproducible readings under the extreme conditions of the cold ethanol plasma fractionation procedure. Adequately reproducible correlations are found between the pH measurements in protein solutions with an ethanol content of up to 40% at temperatures as low as -8 degrees C and the determination in diluted samples at room temperature using the standard procedure."}
{"id": "PMID:8872", "title": "Studies on new process procedures in plasma fractionation on an industrial scale. II. Experiments in concentrating dilute albumin solutions using hollow fiber ultrafiltration.", "content": "Ultrafiltration with a hollow fiber device was studied as an alternative method to the lyophilization or thin-layer distillation techniques in the production of salt-poor, concentrated human albumin preparations for clinical use. A number of process parameters are discussed. Combination of gel filtration and ultrafiltration provides an interesting alternative to the currently used systems.", "contents": "Studies on new process procedures in plasma fractionation on an industrial scale. II. Experiments in concentrating dilute albumin solutions using hollow fiber ultrafiltration. Ultrafiltration with a hollow fiber device was studied as an alternative method to the lyophilization or thin-layer distillation techniques in the production of salt-poor, concentrated human albumin preparations for clinical use. A number of process parameters are discussed. Combination of gel filtration and ultrafiltration provides an interesting alternative to the currently used systems."}
{"id": "PMID:8873", "title": "[The influence of vitamin a, gentamicin and anoxaemia on urinary enzyme excretion (author's transl)].", "content": "The excretion patterns of several urinary enzymes were investigated in the following four experimental groups of Wistar rats and compared with the normal range of each urinary enzyme studied. One group received vitamin A in high dosage; a second group was given vitamin A before and after bilateral clamping of the renal artery for 30 minutes; in the third group the renal arteries were clamped for 30 or 60 minutes; the last group of experimental animals received first low (2mg/kg, 4mg/kg) and subsequently high doses (100 mg/kg) of gentamicin. Vitamin A administration produced no increase in urinary enzyme activity, even in the group of rats with ischaemically-damaged kidneys, where ischaemia (clampin of the arteries) was responsible per se for an increase in enzyme excretion. With low doses of gentamicin the urinary enzymes remained within normal limits, but increased immediately to significantly pathological values after the first dose 100 mg/kg gentamicin.", "contents": "[The influence of vitamin a, gentamicin and anoxaemia on urinary enzyme excretion (author's transl)]. The excretion patterns of several urinary enzymes were investigated in the following four experimental groups of Wistar rats and compared with the normal range of each urinary enzyme studied. One group received vitamin A in high dosage; a second group was given vitamin A before and after bilateral clamping of the renal artery for 30 minutes; in the third group the renal arteries were clamped for 30 or 60 minutes; the last group of experimental animals received first low (2mg/kg, 4mg/kg) and subsequently high doses (100 mg/kg) of gentamicin. Vitamin A administration produced no increase in urinary enzyme activity, even in the group of rats with ischaemically-damaged kidneys, where ischaemia (clampin of the arteries) was responsible per se for an increase in enzyme excretion. With low doses of gentamicin the urinary enzymes remained within normal limits, but increased immediately to significantly pathological values after the first dose 100 mg/kg gentamicin."}
{"id": "PMID:8874", "title": "[Urinary enzyme levels in healthy human subjects and in rats (author's transl)].", "content": "Urinary MDH, LDH, gamma-GT, LAP and muramidase levels were studied in 11 healthy persons with a wide age range and in 51 male Winstar rats weighing 300 to 400 g. Normal ranges of these urinary enzymes were determined and compared with the results of other authors.", "contents": "[Urinary enzyme levels in healthy human subjects and in rats (author's transl)]. Urinary MDH, LDH, gamma-GT, LAP and muramidase levels were studied in 11 healthy persons with a wide age range and in 51 male Winstar rats weighing 300 to 400 g. Normal ranges of these urinary enzymes were determined and compared with the results of other authors."}
{"id": "PMID:8877", "title": "[Cellular immunity against bacteria (intracellular and extracellular parasites) in experimentally aged rats (author's transl)].", "content": "The authors study the activity of RES in rats with Progeria-like syndrome of Selye, at the occasion of a repeated infection with bacteria--intracellular parasites (Brucella abortus 19) and bacteria--extracellular parasites (Diplococcus pneumoniae). They establish that immunization improves the activity of RES of the experimentally aged rats; still, its phagocytic and digestive functions remain by far feebler than those of the rats unsubjected to experimental ageing. By the aged animals the RES insufficiency is more pronounced towards the intracellular bacterium Brucella abortus 19, than towards the extracellular Diplococcus pneumoniae.", "contents": "[Cellular immunity against bacteria (intracellular and extracellular parasites) in experimentally aged rats (author's transl)]. The authors study the activity of RES in rats with Progeria-like syndrome of Selye, at the occasion of a repeated infection with bacteria--intracellular parasites (Brucella abortus 19) and bacteria--extracellular parasites (Diplococcus pneumoniae). They establish that immunization improves the activity of RES of the experimentally aged rats; still, its phagocytic and digestive functions remain by far feebler than those of the rats unsubjected to experimental ageing. By the aged animals the RES insufficiency is more pronounced towards the intracellular bacterium Brucella abortus 19, than towards the extracellular Diplococcus pneumoniae."}
{"id": "PMID:8878", "title": "[Resistance against intra- and extracellular bacteria in experimentally aged rats (author's transl)].", "content": "The authors study the cellular activity of RES against the microbes intracellular and extracellular parasites in rats with pronounced Progeria-like syndrome of Selye. RES of the experimentally aged animals copes, through with a certain delay, with the invading extracellular bacterium Diplococcus pneumoniae, but is utterly helpless against the intracellular microbe Br. abortus 19. These relations are completly inverted in the rats that have not been experimentally aged.", "contents": "[Resistance against intra- and extracellular bacteria in experimentally aged rats (author's transl)]. The authors study the cellular activity of RES against the microbes intracellular and extracellular parasites in rats with pronounced Progeria-like syndrome of Selye. RES of the experimentally aged animals copes, through with a certain delay, with the invading extracellular bacterium Diplococcus pneumoniae, but is utterly helpless against the intracellular microbe Br. abortus 19. These relations are completly inverted in the rats that have not been experimentally aged."}
{"id": "PMID:8879", "title": "[Aminopeptidases in the serum and urine of patients with hyperthyroidism].", "content": "In patients with hyperthyroidism the serum activities of the leucine aminopeptidase (LAP) and the alanine aminopeptidase (AAP) as well as the alanine aminopeptidase excretion in the urine were determined. A significantly increased activity of the leucine aminopeptidase in the serum and an increased excretion of alanine aminopeptidase in the urine were found. The AAP in the serum did not show a significant increase of activity. On account of the changes in the serum and in the urine before and during therapy a low-grade participation of the hepatobiliary and renal systems which are clinically not uppermost is to be assumed. Increased excretion of AAP and hyperthyroidism coincide nearly without exception in out patients. Correlation-statistical investigations make it probable to regard the increased excretion of AAP in the urine as an indirect parameter of the peripheral metabolism in hyperthyroidism.", "contents": "[Aminopeptidases in the serum and urine of patients with hyperthyroidism]. In patients with hyperthyroidism the serum activities of the leucine aminopeptidase (LAP) and the alanine aminopeptidase (AAP) as well as the alanine aminopeptidase excretion in the urine were determined. A significantly increased activity of the leucine aminopeptidase in the serum and an increased excretion of alanine aminopeptidase in the urine were found. The AAP in the serum did not show a significant increase of activity. On account of the changes in the serum and in the urine before and during therapy a low-grade participation of the hepatobiliary and renal systems which are clinically not uppermost is to be assumed. Increased excretion of AAP and hyperthyroidism coincide nearly without exception in out patients. Correlation-statistical investigations make it probable to regard the increased excretion of AAP in the urine as an indirect parameter of the peripheral metabolism in hyperthyroidism."}
{"id": "PMID:8880", "title": "[Vetorial presentation of left-ventricular pressure parameters for the assessment of ventricular function].", "content": "The ventricle function can be established by the vectorial description of left-ventricular pressure parameters or flow sizes, respectively. The vector diagrammes result from the momentaneous pressure within the ventricle on the X-axis and the differentiated pressure curve or the aortic flow, respectively, on the Y-axis. Well surveyable from the vector loop received (LVP/dp/dt) are established dp/dtmax, dp/dtmin, LVPmax, LVEDP as well as the tg of the pressure increase speed or the pressure decrease speed, respectively, pro developed pressure. By way of example medicamentous changes of the vector diagrammes were induced and the parameters mentioned established. The vectorial demonstration of the left-ventricular haemodynamics seems to give additional informations concerning the phase of centraction and relaxation", "contents": "[Vetorial presentation of left-ventricular pressure parameters for the assessment of ventricular function]. The ventricle function can be established by the vectorial description of left-ventricular pressure parameters or flow sizes, respectively. The vector diagrammes result from the momentaneous pressure within the ventricle on the X-axis and the differentiated pressure curve or the aortic flow, respectively, on the Y-axis. Well surveyable from the vector loop received (LVP/dp/dt) are established dp/dtmax, dp/dtmin, LVPmax, LVEDP as well as the tg of the pressure increase speed or the pressure decrease speed, respectively, pro developed pressure. By way of example medicamentous changes of the vector diagrammes were induced and the parameters mentioned established. The vectorial demonstration of the left-ventricular haemodynamics seems to give additional informations concerning the phase of centraction and relaxation"}
{"id": "PMID:8881", "title": "[Round table discussion. Ulcer - vagus - gastrin].", "content": "1. Both gastrin and the vagus nerve play a part in the pathogenesis of the duodenal ulcer. Which of these two factors is of greater significance--this problem is still subject to discussion as is the question whether other factors such as duodenal neutralization are more important than hitherto assumed. 2. At this time no reliable and harmless drugs that speed up the healing of duodenal ulcers and prevent relapses are yet available. Candidates for this are H2 receptor blockers, prostaglandines and possibly substances resembling secretin. 3. Only some of the participants considered it necessary to do endoscopic and radiological follow-ups in duodenal ulcers. 4. Proximal gastric vagotomy for the treatment of duodenal ulcers is still undergoing clinical trials. At present this method should only be used by surgeons with a special interest in gastric surgery who also dispose of the technology and the staff for careful postoperative checks on these patients. The advantages of proximal gastric vagotomy consist in sparing truncation, low mortality and good functional results. 5. In gastric ulcers--contrary to duodenal ones--malignancy should always be suspected. If medical treatment does not lead to complete remission within a few months, surgery must be performed. 6. Many surgeons still prefer resection to vagotomy and excision in the management of gastric ulcers.", "contents": "[Round table discussion. Ulcer - vagus - gastrin]. 1. Both gastrin and the vagus nerve play a part in the pathogenesis of the duodenal ulcer. Which of these two factors is of greater significance--this problem is still subject to discussion as is the question whether other factors such as duodenal neutralization are more important than hitherto assumed. 2. At this time no reliable and harmless drugs that speed up the healing of duodenal ulcers and prevent relapses are yet available. Candidates for this are H2 receptor blockers, prostaglandines and possibly substances resembling secretin. 3. Only some of the participants considered it necessary to do endoscopic and radiological follow-ups in duodenal ulcers. 4. Proximal gastric vagotomy for the treatment of duodenal ulcers is still undergoing clinical trials. At present this method should only be used by surgeons with a special interest in gastric surgery who also dispose of the technology and the staff for careful postoperative checks on these patients. The advantages of proximal gastric vagotomy consist in sparing truncation, low mortality and good functional results. 5. In gastric ulcers--contrary to duodenal ones--malignancy should always be suspected. If medical treatment does not lead to complete remission within a few months, surgery must be performed. 6. Many surgeons still prefer resection to vagotomy and excision in the management of gastric ulcers."}
{"id": "PMID:8882", "title": "[Stress ulcer: clinical aspects, pathogenesis, diagnosis and therapy].", "content": "The frequency, the treatment and the mortality of stress induced ulcers and erosions of the upper alimentary tract are surveyed. The experimental data concerning such ulcers and erosions are reported. Most important is the local mucosal ischaemia with a concomitant reabsorption of H-ions. Intravasal coagulation processes and a local diminution of the Vitamin A content may be additional factors. 37 stress induced bleedings observed in 460 patients of a surgical intensive care unit are analysed. The mortality of the conservatively treated group was 60% and higher than the mortality after operative treatment (42%). The high mortality was due to the associated states of shock, hypoxaemia and sepsis. A prospective study comporting 50 patients of a medical intensive care unit shows the little importance of intravasal coagulation for gastrointestinal bleedings during septicaemia. The possible influence of psychological factors for the induction of stress induced bleedings was analysed on 112 tetraplegics and paraplegics, all under the same conservative treatment comporting high doses of Dexamethason. The frequency of gastrointestinal bleedings was very high in complete traumatic tetraplegia (41%), smaller in complete traumatic paraplegia (16%), much lower in incomplete traumatic and complete non-traumatic lesions.", "contents": "[Stress ulcer: clinical aspects, pathogenesis, diagnosis and therapy]. The frequency, the treatment and the mortality of stress induced ulcers and erosions of the upper alimentary tract are surveyed. The experimental data concerning such ulcers and erosions are reported. Most important is the local mucosal ischaemia with a concomitant reabsorption of H-ions. Intravasal coagulation processes and a local diminution of the Vitamin A content may be additional factors. 37 stress induced bleedings observed in 460 patients of a surgical intensive care unit are analysed. The mortality of the conservatively treated group was 60% and higher than the mortality after operative treatment (42%). The high mortality was due to the associated states of shock, hypoxaemia and sepsis. A prospective study comporting 50 patients of a medical intensive care unit shows the little importance of intravasal coagulation for gastrointestinal bleedings during septicaemia. The possible influence of psychological factors for the induction of stress induced bleedings was analysed on 112 tetraplegics and paraplegics, all under the same conservative treatment comporting high doses of Dexamethason. The frequency of gastrointestinal bleedings was very high in complete traumatic tetraplegia (41%), smaller in complete traumatic paraplegia (16%), much lower in incomplete traumatic and complete non-traumatic lesions."}
{"id": "PMID:8883", "title": "[Interaction between gastrointestinal hormones and endocrine regulation].", "content": "The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a \"long distance\" impact; their role within pathophysiology is also of interest. GIP (\"gastric inhibitory peptide\"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.", "contents": "[Interaction between gastrointestinal hormones and endocrine regulation]. The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a \"long distance\" impact; their role within pathophysiology is also of interest. GIP (\"gastric inhibitory peptide\"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application."}
{"id": "PMID:8884", "title": "[Uterine activity under tocolysis through a beta-sympathomimetic (author's transl)].", "content": "The actual mechanism of tocolytic effect of beta-mimetics is not yet known. While they are able to stop labour, the effect in vitro on myometral filaments is very different. In contrast to this, the socalled Ca++ -antagonists have an excellent relaxing effect on myometrium in vitro, but they are clinically ineffective. To clear up the mechanism of tocolysis, the uterine activity under tocolytic therapy was observed by external tocography. Whereas in normal pregnancy the portion of Braxton-Hicks-contractions and phases of inactivity--equivalent to the intervals of labour -- increases and the portion of Alvarez waves decreases, under tocolysis these changes are not to be found for a long time. The portion of Braxton-Hicks-contractions and phases of inactivity together is smaller than in normal pregnancy. The proportion of Braxton-Hicks-contractions to phases of inactivity corresponds well to normal pregnancy. The changes of uterine activity in normal pregnancy are explained as a process of increasing coordination. The tocolytic effect is regarded as a disturbance of this process.", "contents": "[Uterine activity under tocolysis through a beta-sympathomimetic (author's transl)]. The actual mechanism of tocolytic effect of beta-mimetics is not yet known. While they are able to stop labour, the effect in vitro on myometral filaments is very different. In contrast to this, the socalled Ca++ -antagonists have an excellent relaxing effect on myometrium in vitro, but they are clinically ineffective. To clear up the mechanism of tocolysis, the uterine activity under tocolytic therapy was observed by external tocography. Whereas in normal pregnancy the portion of Braxton-Hicks-contractions and phases of inactivity--equivalent to the intervals of labour -- increases and the portion of Alvarez waves decreases, under tocolysis these changes are not to be found for a long time. The portion of Braxton-Hicks-contractions and phases of inactivity together is smaller than in normal pregnancy. The proportion of Braxton-Hicks-contractions to phases of inactivity corresponds well to normal pregnancy. The changes of uterine activity in normal pregnancy are explained as a process of increasing coordination. The tocolytic effect is regarded as a disturbance of this process."}
{"id": "PMID:8885", "title": "[Effect of arterial hypoxia and acidosis on fibrillation threshold in the cat heart in vivo].", "content": "The influence of severe arterial hypoxia and acidosis on the fibrillation threshold was checked in 22 cats. Two groups were formed: in 10 cats (group I) acidosis was produced by 2-N lactic acid infusion; in the second group of 12 animals the respirator was turned off for 60 seconds, thus producing a low arterial PO2. If hypoxia and acidosis were severe enough, the fibrillation threshold was significantly lowered in either group. The pathophysiological mechanisms of these findings are discussed.", "contents": "[Effect of arterial hypoxia and acidosis on fibrillation threshold in the cat heart in vivo]. The influence of severe arterial hypoxia and acidosis on the fibrillation threshold was checked in 22 cats. Two groups were formed: in 10 cats (group I) acidosis was produced by 2-N lactic acid infusion; in the second group of 12 animals the respirator was turned off for 60 seconds, thus producing a low arterial PO2. If hypoxia and acidosis were severe enough, the fibrillation threshold was significantly lowered in either group. The pathophysiological mechanisms of these findings are discussed."}
{"id": "PMID:8886", "title": "Reversible transformation of precipitated and nonprecipitated lipoproteins recombined from proteins and lipids of erythrocyte membranes.", "content": "The sedimentation at low speed centrifugation of a lipoprotein recombined from the lipids and the strongly bound proteins of the human erythrocyte membrane depends on pH: between 4.5 and 6.0, most of the liproprotein sediments, whereas at pH 7.0-8.5, up to 90% remains in the supernatant. Precipitation of the lipoprotein can be reversed by increasing the pH, followed by a brief sonication. The mobility of spin-labelled protein groups in the lipoprotein increases with increasing pH. This mobility increase is also reversible and is of equal magnitude in precipitated and nonprecipitated recombinates. It is concluded that, because of these reversibilities, determination of the yield of liproprotein formation in recombination experiments must include analysis of both precipitated and nonprecipitated lipoproteins.", "contents": "Reversible transformation of precipitated and nonprecipitated lipoproteins recombined from proteins and lipids of erythrocyte membranes. The sedimentation at low speed centrifugation of a lipoprotein recombined from the lipids and the strongly bound proteins of the human erythrocyte membrane depends on pH: between 4.5 and 6.0, most of the liproprotein sediments, whereas at pH 7.0-8.5, up to 90% remains in the supernatant. Precipitation of the lipoprotein can be reversed by increasing the pH, followed by a brief sonication. The mobility of spin-labelled protein groups in the lipoprotein increases with increasing pH. This mobility increase is also reversible and is of equal magnitude in precipitated and nonprecipitated recombinates. It is concluded that, because of these reversibilities, determination of the yield of liproprotein formation in recombination experiments must include analysis of both precipitated and nonprecipitated lipoproteins."}
{"id": "PMID:8887", "title": "Galactans and anti-galactans from invertebrates.", "content": "Antibody-like substances with anti-carbohydrate specificities directed against different structures of galactans have been detected in several invertebrates.", "contents": "Galactans and anti-galactans from invertebrates. Antibody-like substances with anti-carbohydrate specificities directed against different structures of galactans have been detected in several invertebrates."}
{"id": "PMID:8888", "title": "[\"Synthetical\" aiptasia mutabilis RAPP (coelenterata) (author's transl)].", "content": "After being cultivated in the dark for some months and after being fed with food free of carotenoids during the time Aiptasia mutabilis (Coelenterata) loses its symbiontic algae (rich in brown fucoxanthin) and becomes transparent white. This disarranged symbiosis may be regenerated under light cultivation by adding different species of Chlorophyceae (Chlorella, Dunaliella) and chrysophyceae (Ochromonas, Cyclotella), but not of Cyanophyceae (Anabaena, Nostoc, Oscillatoria, Anacystis). - This changeable life system between coelenterata and algae may be a good example for further studies of the endosymbiosis problem.", "contents": "[\"Synthetical\" aiptasia mutabilis RAPP (coelenterata) (author's transl)]. After being cultivated in the dark for some months and after being fed with food free of carotenoids during the time Aiptasia mutabilis (Coelenterata) loses its symbiontic algae (rich in brown fucoxanthin) and becomes transparent white. This disarranged symbiosis may be regenerated under light cultivation by adding different species of Chlorophyceae (Chlorella, Dunaliella) and chrysophyceae (Ochromonas, Cyclotella), but not of Cyanophyceae (Anabaena, Nostoc, Oscillatoria, Anacystis). - This changeable life system between coelenterata and algae may be a good example for further studies of the endosymbiosis problem."}
{"id": "PMID:8889", "title": "Studies on the undecapeptide of ferricytochrome c using ESR, M\u00f6ssbauer and visible spectroscopies.", "content": "The ESR, M\u00f6ssbauer, and visible spectra of the undecapeptide of ferricytochrome c (HPp) were measured for both the solid peptide and solutions of the peptide at pH 1.5, 7, and 10. At the low pH, the iron exists in the HPp in the high-spin species. At neutral and alkaline pHs, the low-spin ferric species predominate. The results of these measurements support the previous suggestions concerning the ligands in the fifth and sixth position of HPp at the neutral and alkaline pHs. The spectra of lyophilized preparations of HPp show the presence of both high and low-spin ferric species. The study of the M\u00f6ssbauer spectra of the lyohilized preparations as function of temperature shows that there exists a spin-spin equilibrium between the two spin states. The relative amounts of the two components vary with the preparation. In these preparations there exist two components, one of which exists in the equilibrium mixture and the second in the high-spin form.", "contents": "Studies on the undecapeptide of ferricytochrome c using ESR, M\u00f6ssbauer and visible spectroscopies. The ESR, M\u00f6ssbauer, and visible spectra of the undecapeptide of ferricytochrome c (HPp) were measured for both the solid peptide and solutions of the peptide at pH 1.5, 7, and 10. At the low pH, the iron exists in the HPp in the high-spin species. At neutral and alkaline pHs, the low-spin ferric species predominate. The results of these measurements support the previous suggestions concerning the ligands in the fifth and sixth position of HPp at the neutral and alkaline pHs. The spectra of lyophilized preparations of HPp show the presence of both high and low-spin ferric species. The study of the M\u00f6ssbauer spectra of the lyohilized preparations as function of temperature shows that there exists a spin-spin equilibrium between the two spin states. The relative amounts of the two components vary with the preparation. In these preparations there exist two components, one of which exists in the equilibrium mixture and the second in the high-spin form."}
{"id": "PMID:8894", "title": "Studies on Hymenolepis microstoma in vitro. II. Effect of yeast extract on development and maturation.", "content": "Four day old in vivo Hymenolepis microstoma were cultured in vitro for 6 days in media containing 2, 1, 0.5 and 0.1% yeast extract. Worms from all groups including control group increased in length and produced nearly equivalent numbers of proglottids. However, worms grown in yeast extract added media produced significantly more mature proglottids and were heavier than those in the control medium. The possibility of pyridoxin involvement has been contemplated. Effects of osmotic pressure and pH on the development of worms are discussed.", "contents": "Studies on Hymenolepis microstoma in vitro. II. Effect of yeast extract on development and maturation. Four day old in vivo Hymenolepis microstoma were cultured in vitro for 6 days in media containing 2, 1, 0.5 and 0.1% yeast extract. Worms from all groups including control group increased in length and produced nearly equivalent numbers of proglottids. However, worms grown in yeast extract added media produced significantly more mature proglottids and were heavier than those in the control medium. The possibility of pyridoxin involvement has been contemplated. Effects of osmotic pressure and pH on the development of worms are discussed."}
{"id": "PMID:8891", "title": "The use of 1-anilino-8-naphthalene sulfonate as fluorescent probe for conformational studies on ribulose-1,5-bisphosphate carboxylase.", "content": "The influence of Mg2+ ions and temperature on the structure of the enzyme ribulose-1,5-bisphosphate carboxylase was investigated using the fluorescent probe 1-anilino-8-naphthalene sulfonate (ANS). The binding of ANS to the enzyme molecule caused a significant increase of fluorescence emission which was further enhanced by the addition of Mg2+. The temperature dependence of the fluorescence emission indicated a conformational change of the enzyme between 12 and 24 degrees C. The Mg2+ and the temperature effects were additive. ANS itself did not change the conformation of the enzyme. The influence of the substrates carbon dioxide and ribulose-1,5-bisphosphate, and the effect of the pH of the medium and of a sulfhydryl reducing reagent on fluorescence emission were analysed.", "contents": "The use of 1-anilino-8-naphthalene sulfonate as fluorescent probe for conformational studies on ribulose-1,5-bisphosphate carboxylase. The influence of Mg2+ ions and temperature on the structure of the enzyme ribulose-1,5-bisphosphate carboxylase was investigated using the fluorescent probe 1-anilino-8-naphthalene sulfonate (ANS). The binding of ANS to the enzyme molecule caused a significant increase of fluorescence emission which was further enhanced by the addition of Mg2+. The temperature dependence of the fluorescence emission indicated a conformational change of the enzyme between 12 and 24 degrees C. The Mg2+ and the temperature effects were additive. ANS itself did not change the conformation of the enzyme. The influence of the substrates carbon dioxide and ribulose-1,5-bisphosphate, and the effect of the pH of the medium and of a sulfhydryl reducing reagent on fluorescence emission were analysed."}
{"id": "PMID:8890", "title": "Physiological effects of sucrose substitutes and artificial sweeteners on growth pattern and acid production of glucose-grown Streptococcus mutans strains in vitro.", "content": "The synergistic effects of four sucrose substitutes, polysorbate and five artificial sweeteners were studied in vitro on growth pattern and acid production of seven glucose-grown Streptococcus mutans strains, representing the five serological groups after Bratthall. Four distinct growth patterns during glucose fermentation were observed: high rate of growth with low acid production, moderate growth rate with moderate acid production, moderate growth rate with high acid production, and slow rate of growth with moderate acid production. Depending on the strain used, the final OD at 546 nm ranged from 0.55 to 0.99 and the final pH of the medium varied between 4.65 and 4.15. While added sucrose substitutes, with exceptions, usually enhanced growth rate, most artificial sweeteners suppressed or, at higher concentrations, even inhibited growth of S. mutans; addition of polysorbate to the medium always increased growth rate of S. mutans significantly. The presence of sucrose substitutes during glucose fermentation had no effect on final pH of the medium, but addition of artificial sweeteners, especially sodium saccharin, elevated final pH up to 1.8 units. The observed physiological patterns and differences within the several strains of S. mutans during glucose fermentation in vitro do not necessarily relate to the five serological groups of the species.", "contents": "Physiological effects of sucrose substitutes and artificial sweeteners on growth pattern and acid production of glucose-grown Streptococcus mutans strains in vitro. The synergistic effects of four sucrose substitutes, polysorbate and five artificial sweeteners were studied in vitro on growth pattern and acid production of seven glucose-grown Streptococcus mutans strains, representing the five serological groups after Bratthall. Four distinct growth patterns during glucose fermentation were observed: high rate of growth with low acid production, moderate growth rate with moderate acid production, moderate growth rate with high acid production, and slow rate of growth with moderate acid production. Depending on the strain used, the final OD at 546 nm ranged from 0.55 to 0.99 and the final pH of the medium varied between 4.65 and 4.15. While added sucrose substitutes, with exceptions, usually enhanced growth rate, most artificial sweeteners suppressed or, at higher concentrations, even inhibited growth of S. mutans; addition of polysorbate to the medium always increased growth rate of S. mutans significantly. The presence of sucrose substitutes during glucose fermentation had no effect on final pH of the medium, but addition of artificial sweeteners, especially sodium saccharin, elevated final pH up to 1.8 units. The observed physiological patterns and differences within the several strains of S. mutans during glucose fermentation in vitro do not necessarily relate to the five serological groups of the species."}
{"id": "PMID:8892", "title": "Tautomerism of isoguanosine and solvent-induced keto-enol equilibrium.", "content": "Ultraviolet and infrared absorption spectroscopy, in aqueous and non-aqueous media, have been employed to study the tautomerism of 9-substituted isoguanines, including the nucleoside isoguanosine. With the aid of a series of model compounds, it was shown that 9-substituted isoguanines, and isoguanosine, in aqueous medium are predominantly in the form N (1) H, 2-keto-6-amino. In dioxane solution the tautomeric equilibrium is shifted in the direction of the enol form. The shift towards this form is accentuated for those analogues in which the exocyclic amino group is methylated. With the aid of N6,N6, 9-trimethylisoguanine, and 9-octyl analogue, the tautomeric constant was studied as a function of concentration, temperature, and solvent polarity, and the results applied to evaluate the tautomeric equilibria of 9-methylisoguanine and isoguanosine as a function of these variables. In general the enol form is favoured by a decrease in solvent polarity, by a decrease in concentration in dioxane, or an increase in temperature in chloroform solution. Syntheses are described for several N6 amino and methylamino derivatives of 2-methoxy-9-methylpurine, and 3-methyl-5-oxo-7,8-dihydroimidazo (2,1-i) purine, which served as an analogue of the unavailable 1,9-dimethylisoguanine.", "contents": "Tautomerism of isoguanosine and solvent-induced keto-enol equilibrium. Ultraviolet and infrared absorption spectroscopy, in aqueous and non-aqueous media, have been employed to study the tautomerism of 9-substituted isoguanines, including the nucleoside isoguanosine. With the aid of a series of model compounds, it was shown that 9-substituted isoguanines, and isoguanosine, in aqueous medium are predominantly in the form N (1) H, 2-keto-6-amino. In dioxane solution the tautomeric equilibrium is shifted in the direction of the enol form. The shift towards this form is accentuated for those analogues in which the exocyclic amino group is methylated. With the aid of N6,N6, 9-trimethylisoguanine, and 9-octyl analogue, the tautomeric constant was studied as a function of concentration, temperature, and solvent polarity, and the results applied to evaluate the tautomeric equilibria of 9-methylisoguanine and isoguanosine as a function of these variables. In general the enol form is favoured by a decrease in solvent polarity, by a decrease in concentration in dioxane, or an increase in temperature in chloroform solution. Syntheses are described for several N6 amino and methylamino derivatives of 2-methoxy-9-methylpurine, and 3-methyl-5-oxo-7,8-dihydroimidazo (2,1-i) purine, which served as an analogue of the unavailable 1,9-dimethylisoguanine."}
{"id": "PMID:8893", "title": "Isolation and properties of yeast mutants with highly efficient thymidylate utilization.", "content": "A screening procedure is presented which allows the isolation of yeast mutants (typ tir) with highly efficient utilization of exogenous deoxythymidine-5'-monophosphate (5'-dTMP) (greater than 50%). Data are given concerning the phenomenon of 5'-dTMP utilization in general: (i) The ability of S. cerevisiae to incorporate exogenous 5'-dTMP was found to already to be a wild type feature of this yeast, i.e. apparently not to be due to any mutation such as typ, tup, tmp, per or tum. Consequently these mutations are interpreted as amplifiers of a pre-given wild type potency. So far eight stages of 5'-dTMP utilization were detected as classified by the optimal 5'-dTMP requirement, with 5'-dTMP biosynthesis blocked, of the corresponding mutant strains isolated. All of them fit well into a mathematical series of the type \"2n x 1.5\" (n = 0, 1, 2, ..., 11), where the product term for n = 11 represents the 5'-dTMP requirement (mug/ml) of the best 5'-dTMP utilizing wild type strain found. (ii) Amplification of the 5'-dTMP utilizing potency obviously is due to any genetically determined alteration of the yeast 5'-dTMP uptaking principle itself or of physiological processes accompanying the monophosphate's uptake. (iii) The functioning of 5'-dTMP uptake requires acidic (less than or equal to pH 6) conditions in the yeast cell's outer environment. (iv) Some yeast typ and typ tlr mutants were found to exhibit a more or less pronounced sensitivity towards exogenously offered 5'-dTMP. The response of a sensitive strain towards inhibitory concentrations of the nucleotide apparently is co-conditioned by the presence or absence of thymidylate biosynthesis. With 5'-dTMP biosynthesis blocked the 5'-dTMP mediated inhibition is a permanent one and finally leads to the death of a cell. With a functioning thymidylate biosynthesis, in contrast, the inhibition is only temporary. (v) Yeast typ or typ tlr strains were observed to dephosphorylate exogenous 5'-dTMP to thymidine due to a phosphatase activity which cannot be eliminated at pH 7 + 70 mM inorganic phosphate conditions in the growth medium. This 5'-dTMP cleavage obviously occurs outside the cell and does not seem to be correlated both to the monophosphate's uptake and to the phenomenon of 5'-dTMP sensitivity. The destruction of 5'-dTMP does not disturb (5'-dTMP) DNA-specific labelling.", "contents": "Isolation and properties of yeast mutants with highly efficient thymidylate utilization. A screening procedure is presented which allows the isolation of yeast mutants (typ tir) with highly efficient utilization of exogenous deoxythymidine-5'-monophosphate (5'-dTMP) (greater than 50%). Data are given concerning the phenomenon of 5'-dTMP utilization in general: (i) The ability of S. cerevisiae to incorporate exogenous 5'-dTMP was found to already to be a wild type feature of this yeast, i.e. apparently not to be due to any mutation such as typ, tup, tmp, per or tum. Consequently these mutations are interpreted as amplifiers of a pre-given wild type potency. So far eight stages of 5'-dTMP utilization were detected as classified by the optimal 5'-dTMP requirement, with 5'-dTMP biosynthesis blocked, of the corresponding mutant strains isolated. All of them fit well into a mathematical series of the type \"2n x 1.5\" (n = 0, 1, 2, ..., 11), where the product term for n = 11 represents the 5'-dTMP requirement (mug/ml) of the best 5'-dTMP utilizing wild type strain found. (ii) Amplification of the 5'-dTMP utilizing potency obviously is due to any genetically determined alteration of the yeast 5'-dTMP uptaking principle itself or of physiological processes accompanying the monophosphate's uptake. (iii) The functioning of 5'-dTMP uptake requires acidic (less than or equal to pH 6) conditions in the yeast cell's outer environment. (iv) Some yeast typ and typ tlr mutants were found to exhibit a more or less pronounced sensitivity towards exogenously offered 5'-dTMP. The response of a sensitive strain towards inhibitory concentrations of the nucleotide apparently is co-conditioned by the presence or absence of thymidylate biosynthesis. With 5'-dTMP biosynthesis blocked the 5'-dTMP mediated inhibition is a permanent one and finally leads to the death of a cell. With a functioning thymidylate biosynthesis, in contrast, the inhibition is only temporary. (v) Yeast typ or typ tlr strains were observed to dephosphorylate exogenous 5'-dTMP to thymidine due to a phosphatase activity which cannot be eliminated at pH 7 + 70 mM inorganic phosphate conditions in the growth medium. This 5'-dTMP cleavage obviously occurs outside the cell and does not seem to be correlated both to the monophosphate's uptake and to the phenomenon of 5'-dTMP sensitivity. The destruction of 5'-dTMP does not disturb (5'-dTMP) DNA-specific labelling."}
{"id": "PMID:8899", "title": "[Electron microscopic findings in a polyneuropathy complicating panarteritis nodosa].", "content": "Electromicroscopial changes were observed in arterioles, nerves, and striated skeleton muscle cells in a case of clinically and histologically definite polyarteritis nodosa with polyneuropathy. Inflammatory infiltrates were found in and around arteriolar walls; motor nerves were partly demarkated and presynaptic motor endplates were degenerated. The myofibrills of skeleton muscle cells showed a disorganization that is regarded as the morphological substrate for the clinically observed muscular weakness in this case.", "contents": "[Electron microscopic findings in a polyneuropathy complicating panarteritis nodosa]. Electromicroscopial changes were observed in arterioles, nerves, and striated skeleton muscle cells in a case of clinically and histologically definite polyarteritis nodosa with polyneuropathy. Inflammatory infiltrates were found in and around arteriolar walls; motor nerves were partly demarkated and presynaptic motor endplates were degenerated. The myofibrills of skeleton muscle cells showed a disorganization that is regarded as the morphological substrate for the clinically observed muscular weakness in this case."}
{"id": "PMID:8935", "title": "[Treatment of threatened early abortion (6th-16th week of pregnancy) of Th 1165a (Partusisten)].", "content": "The report is presented about the treatment of the abortus imminens in the early pregnancy between the 6th and 16th weeks with a new tocolytical substance Th 1165a (Partusisten) on the basis of 61 patients. 40 of the patients reached full term delivery (41 new borns). All new borns except one with multiple chromosomal abnormalities were without any pathological evidence. Two pregnancies terminated into abortion. We could achieve tocolysis in each and every case consistantly by a special worked out scheme. Side effects, which are described due to other beta-adrenergic substances were minimal. Eventual cardiovascular side effects were prevented by additional administration of Isoptin. The results are good. Therefore the administration of Partusisten in the treatment of the imminent abortions in the early pregnancy between the 6th and 16th weeks is sensefull.", "contents": "[Treatment of threatened early abortion (6th-16th week of pregnancy) of Th 1165a (Partusisten)]. The report is presented about the treatment of the abortus imminens in the early pregnancy between the 6th and 16th weeks with a new tocolytical substance Th 1165a (Partusisten) on the basis of 61 patients. 40 of the patients reached full term delivery (41 new borns). All new borns except one with multiple chromosomal abnormalities were without any pathological evidence. Two pregnancies terminated into abortion. We could achieve tocolysis in each and every case consistantly by a special worked out scheme. Side effects, which are described due to other beta-adrenergic substances were minimal. Eventual cardiovascular side effects were prevented by additional administration of Isoptin. The results are good. Therefore the administration of Partusisten in the treatment of the imminent abortions in the early pregnancy between the 6th and 16th weeks is sensefull."}
{"id": "PMID:8936", "title": "[Effect of the vernix caseosa content in the amniotic fluid on the actual pH-value of the amniotic fluid].", "content": "To determine the eventual influence of the vernix caseosa on the actual pH-value of the amniotic fluid we compared the pH-value of 50 samples of non-filtered amniotic  fluid and the pH-values of filtered portions of the same samples. The samples were taken after delivery of the fetus. We found a distinct shift of the pH-values of the filtered portions to alkaline values. It is recommended that these results should be taken into consideration in laboratory analysis of amniotic fluid.", "contents": "[Effect of the vernix caseosa content in the amniotic fluid on the actual pH-value of the amniotic fluid]. To determine the eventual influence of the vernix caseosa on the actual pH-value of the amniotic fluid we compared the pH-value of 50 samples of non-filtered amniotic  fluid and the pH-values of filtered portions of the same samples. The samples were taken after delivery of the fetus. We found a distinct shift of the pH-values of the filtered portions to alkaline values. It is recommended that these results should be taken into consideration in laboratory analysis of amniotic fluid."}
{"id": "PMID:8938", "title": "[Serologic properties of strains of Cl. perfringens isolated from the intestinal contents of healthy subjects].", "content": "A study was made of the quantitative content in the intestine of C1. perfringens strains in 6 healthy persons who stayed in a hermetically sealed space for 1 month and for 1 year. C1. perfingens strains were isolated from the fecal samples of each of the volunteers at various periods of the trial. A total of 570 strains of C1. perfringens of type A with anticellular sera obtained to the strains of various serological groups were studied. Serological properties of C1. perfringens strains of type A present in the intestinal contents of man were nonhomogeneous. This pointed to the simultaneous presence in the intestine of strains belonging to several serological types. A partial or complete replacement of one strain by another (differing by serological properties) occurred in the course of not over one month. C1. perfringens strains of type A present in the intestine of each volunteer were subdivided into serological types individual for each of the persons under observation. This pointed to the fact than no interexchange of strains of the mentioned bacteria occurred between different persons in the hermetically sealed space.", "contents": "[Serologic properties of strains of Cl. perfringens isolated from the intestinal contents of healthy subjects]. A study was made of the quantitative content in the intestine of C1. perfringens strains in 6 healthy persons who stayed in a hermetically sealed space for 1 month and for 1 year. C1. perfingens strains were isolated from the fecal samples of each of the volunteers at various periods of the trial. A total of 570 strains of C1. perfringens of type A with anticellular sera obtained to the strains of various serological groups were studied. Serological properties of C1. perfringens strains of type A present in the intestinal contents of man were nonhomogeneous. This pointed to the simultaneous presence in the intestine of strains belonging to several serological types. A partial or complete replacement of one strain by another (differing by serological properties) occurred in the course of not over one month. C1. perfringens strains of type A present in the intestine of each volunteer were subdivided into serological types individual for each of the persons under observation. This pointed to the fact than no interexchange of strains of the mentioned bacteria occurred between different persons in the hermetically sealed space."}
{"id": "PMID:8940", "title": "[Resistance to levomycetin and activity of several enzymes in Escherichia coli and the agent of plague].", "content": "The authors compared the activity of acetyl-CoA-synthetase and of the enzymes belonging to the group of asparaginic acid in levomycetin sensitive and resistant strains of Y. pestis and E. coli. There were revealed marked differences in the activity of aspartase, fumarase, synthetase and desamidase of L-asparagin, and also of the enzyme activated by acetate in the E. coli strains with plasmide resistance. Transmission of R-factor to the pestis was accompanied by decomposition of L-asparadein, formation of AC-CoA. At the same time transformation of L-asparaginic acid catalyzed by aspartase remained on the same low level in the sensitive pestis cultures and their variants with the R-factor. When the resistance was controlled by chromosomal resistance markers, the activity of the enzymes providing formation of L-asparagic acid, its amide and L-malic acid showed no significant change. In chromosomal type of resistance in the mutants of pestis and E. coli the acetyl-CoA-synthetase reaction was as a rule somewhat increased.", "contents": "[Resistance to levomycetin and activity of several enzymes in Escherichia coli and the agent of plague]. The authors compared the activity of acetyl-CoA-synthetase and of the enzymes belonging to the group of asparaginic acid in levomycetin sensitive and resistant strains of Y. pestis and E. coli. There were revealed marked differences in the activity of aspartase, fumarase, synthetase and desamidase of L-asparagin, and also of the enzyme activated by acetate in the E. coli strains with plasmide resistance. Transmission of R-factor to the pestis was accompanied by decomposition of L-asparadein, formation of AC-CoA. At the same time transformation of L-asparaginic acid catalyzed by aspartase remained on the same low level in the sensitive pestis cultures and their variants with the R-factor. When the resistance was controlled by chromosomal resistance markers, the activity of the enzymes providing formation of L-asparagic acid, its amide and L-malic acid showed no significant change. In chromosomal type of resistance in the mutants of pestis and E. coli the acetyl-CoA-synthetase reaction was as a rule somewhat increased."}
{"id": "PMID:8941", "title": "Hypophyso-gonadal function in the cryptorchid child: differences between unilateral and bilateral cryptorchids.", "content": "In 22 normal boys, 33 unilateral and 14 bilateral cryptorchids, a gonadal function test (2000 IU of HCG im each day for three days and assays of plasma testosterone and plasma oestradiol-17beta before and after the HCG administration) as well as an LH-RH test were carried out. In 60% of the cases, both normal and cryptorchid boys, plasma oestradiol-17beta (both in basal conditions and after stimulus) were found to be less than the sensitivity (5 pg/ml) of the method, While the plasma testosterone was similar under basal conditions in the three groups of children, after HCG it was significantly lower than the mean value of the control group only in the bilateral cryptorchids. The testosterone levels, both under basal conditions and after stimulus, are correlated to bone age only in the normal boys and in the unilateral cryptorchids. There were no significant differences among the various groups for either LH and FSH both under basal conditions and after LH-RH. The LH curve area during the LH-RH test is in correlation with bone age only in the normal children.", "contents": "Hypophyso-gonadal function in the cryptorchid child: differences between unilateral and bilateral cryptorchids. In 22 normal boys, 33 unilateral and 14 bilateral cryptorchids, a gonadal function test (2000 IU of HCG im each day for three days and assays of plasma testosterone and plasma oestradiol-17beta before and after the HCG administration) as well as an LH-RH test were carried out. In 60% of the cases, both normal and cryptorchid boys, plasma oestradiol-17beta (both in basal conditions and after stimulus) were found to be less than the sensitivity (5 pg/ml) of the method, While the plasma testosterone was similar under basal conditions in the three groups of children, after HCG it was significantly lower than the mean value of the control group only in the bilateral cryptorchids. The testosterone levels, both under basal conditions and after stimulus, are correlated to bone age only in the normal boys and in the unilateral cryptorchids. There were no significant differences among the various groups for either LH and FSH both under basal conditions and after LH-RH. The LH curve area during the LH-RH test is in correlation with bone age only in the normal children."}
{"id": "PMID:8942", "title": "Halothane anaesthesia in caesarean section.", "content": "The safety and efficacy of halothane anaesthesia were investigated in 97 caesarean sections using 0.4-0.6% halothane added to a mixture of 61 N2O/3-4 1 O2. The administration of halothane was initiated before intubation and terminated immediately prior to delivery. Only one patient reported memories from the operation. The mean Apgar score 1 min after delivery (8.5) was significantly better than that (8.2) in 100 caesarean sections in which a mixture of 71 N2O/3 1 O2 was used. In 17 caesarean sections, the halothane concentrations were examined after 0.9% halothane had been given for exactly 1 min after intubation. It was found that halothane reached and passed the placenta after only 1 min. The levels in the maternal artery and umbilical vein were comparable. The levels in the maternal artery, maternal vein and umbilical vein were markedly higher than in the umbilical artery, which indicated an accumulation of halothane in the foetal tissues. However, due to the vigour of the newborn, halothane concentrations 10 min after birth were very low. The half-life of halothane in the maternal circulation was approximately 1 min with the described method of administration. Blood gas determinations, which were made in seven newborns, proved satisfactory.", "contents": "Halothane anaesthesia in caesarean section. The safety and efficacy of halothane anaesthesia were investigated in 97 caesarean sections using 0.4-0.6% halothane added to a mixture of 61 N2O/3-4 1 O2. The administration of halothane was initiated before intubation and terminated immediately prior to delivery. Only one patient reported memories from the operation. The mean Apgar score 1 min after delivery (8.5) was significantly better than that (8.2) in 100 caesarean sections in which a mixture of 71 N2O/3 1 O2 was used. In 17 caesarean sections, the halothane concentrations were examined after 0.9% halothane had been given for exactly 1 min after intubation. It was found that halothane reached and passed the placenta after only 1 min. The levels in the maternal artery and umbilical vein were comparable. The levels in the maternal artery, maternal vein and umbilical vein were markedly higher than in the umbilical artery, which indicated an accumulation of halothane in the foetal tissues. However, due to the vigour of the newborn, halothane concentrations 10 min after birth were very low. The half-life of halothane in the maternal circulation was approximately 1 min with the described method of administration. Blood gas determinations, which were made in seven newborns, proved satisfactory."}
{"id": "PMID:8943", "title": "The haemodynamic effects of unsupplemented nitrous oxide-oxygen-relaxant anaesthesia in cardiac patients.", "content": "The effect on the systemic and pulmonary circulation of unsupplemented nitrous oxide in about 30% oxygen, with and without IPPV, was investigated in five cardiac patients and compared with control periods at rest with air breathing. The results of this investigation show that nitrous oxide in conventional oxygen concentration does not cause any great haemodynamic changes. During tracheal intubation, however, significant increases in both systemic and pulmonary blood pressures were registered. However, these pressures reverted to the control values immediately after the tracheal intubation. The results of this study support many earlier clinicaly good experiences obtained when using this conventional nitrous oxide-oxygen mixture in cardiac patients.", "contents": "The haemodynamic effects of unsupplemented nitrous oxide-oxygen-relaxant anaesthesia in cardiac patients. The effect on the systemic and pulmonary circulation of unsupplemented nitrous oxide in about 30% oxygen, with and without IPPV, was investigated in five cardiac patients and compared with control periods at rest with air breathing. The results of this investigation show that nitrous oxide in conventional oxygen concentration does not cause any great haemodynamic changes. During tracheal intubation, however, significant increases in both systemic and pulmonary blood pressures were registered. However, these pressures reverted to the control values immediately after the tracheal intubation. The results of this study support many earlier clinicaly good experiences obtained when using this conventional nitrous oxide-oxygen mixture in cardiac patients."}
{"id": "PMID:8944", "title": "Histochemical studies on the adrenal glands of the marmosets (Callithrix jacchus and Callithrix penicillata).", "content": "The histrochemistry of the adrenal glands was studied in four adult male marmosets (two Callithrix jacchus and two Callithrix penicillata). It was impossible to demonstrate any reactivity to UDPG-GT, ADH, alanyl aminopeptidase, leucine aminopeptidase, xilitol (NAD-dependent) dehydrogenase, beta-glucuronidase and aryl-sulfatase in these glands. Total phosphorylase was found in scattered cells of the glomerulosa and adjacent outer fasciculata of one C. penicillata. The dehydrogenases (LDH, G-6-PDH,6-PGDH, NADPH2-TR,ICDH,SDH,NADH2-TR, alpha-GPDH, beta-OHBDH) as well as the hydrolases (except alkaline phosphatase, ATPase, and acetylcholinesterase) showed a stonger reactivity in the cortical part. Some hydrolases (naphthol acetate esterase, acid phosphatase) and cytochrome oxidase were less reactive in the zona glomerulosa, where the dehydrogenases were more abundant. The outer fasciculata and the reticularis also showed a strong dehydrogenase reactivity.", "contents": "Histochemical studies on the adrenal glands of the marmosets (Callithrix jacchus and Callithrix penicillata). The histrochemistry of the adrenal glands was studied in four adult male marmosets (two Callithrix jacchus and two Callithrix penicillata). It was impossible to demonstrate any reactivity to UDPG-GT, ADH, alanyl aminopeptidase, leucine aminopeptidase, xilitol (NAD-dependent) dehydrogenase, beta-glucuronidase and aryl-sulfatase in these glands. Total phosphorylase was found in scattered cells of the glomerulosa and adjacent outer fasciculata of one C. penicillata. The dehydrogenases (LDH, G-6-PDH,6-PGDH, NADPH2-TR,ICDH,SDH,NADH2-TR, alpha-GPDH, beta-OHBDH) as well as the hydrolases (except alkaline phosphatase, ATPase, and acetylcholinesterase) showed a stonger reactivity in the cortical part. Some hydrolases (naphthol acetate esterase, acid phosphatase) and cytochrome oxidase were less reactive in the zona glomerulosa, where the dehydrogenases were more abundant. The outer fasciculata and the reticularis also showed a strong dehydrogenase reactivity."}
{"id": "PMID:8945", "title": "Alkaline phosphatase activity in the human tonsils and its relation to tonsillar diseases.", "content": "Alkaline phosphatase activity was examined in the human tonsils in fetal life and after repeated attacks of acute tonsillitis and in quinsy. Gomori's metal precipitate technique was used to demonstrate the phosphatase activity using four different substrates: sodium beta-glycerophosphate and adenosine triphosphate at pH 9, riboflavin 5-phosphate at pH 9.2 and 5-monophosphoric acid at pH 8.3. (2) The phosphatase activity differs somewhat according to the phosphate ester used as a substrate illustrating an example of 'substrate specificity'. (3) Alkaline phosphatase activity was increased in the case of both acute and chronic inflammation. This increase has been discussed in relation to such phenomena as transformation of lymphocytes into macrophages and antibody formation.", "contents": "Alkaline phosphatase activity in the human tonsils and its relation to tonsillar diseases. Alkaline phosphatase activity was examined in the human tonsils in fetal life and after repeated attacks of acute tonsillitis and in quinsy. Gomori's metal precipitate technique was used to demonstrate the phosphatase activity using four different substrates: sodium beta-glycerophosphate and adenosine triphosphate at pH 9, riboflavin 5-phosphate at pH 9.2 and 5-monophosphoric acid at pH 8.3. (2) The phosphatase activity differs somewhat according to the phosphate ester used as a substrate illustrating an example of 'substrate specificity'. (3) Alkaline phosphatase activity was increased in the case of both acute and chronic inflammation. This increase has been discussed in relation to such phenomena as transformation of lymphocytes into macrophages and antibody formation."}
{"id": "PMID:8946", "title": "Amperometric and polarographic study of the SH-activity of MEPRIN (alpha-mercapto-propionylglycine).", "content": "The SH-groups of alpha-mercapto-propionylglycine (MEPRIN) are remarkably stable in diluted solution either at room temperature or at 50 degrees C, even if storing takes place under air-bubbling. The SH-activity was measured by polarographic method and amperometric titration. Neutralization of the carboxyl group decreases the stability of the sulfhydryl groupings. Evaporation of neutralized solution leads to a 30--50 per cent decrease of SH-activity. Lyophilization reduces this loss by 10--15 per cent. Neutralization is best carried out in the absence of oxygen; in this case, 94 per cent of the sulfhydryl activity will persists, irrespective of the pH. The dissociation constant of MEPRIN-SH is pK' = 8.47. The SH-stability of the product is satisfactory when neutralized in nitrogen atmosphere to pH 3--5; a loss of only 5 per cent can be expected after storing in an oxygen-free 10(-3) molar solution for 144 hours. Between pH 6 and 8 this value is 31 per cent on the average, while at pH 9 it is more favorable again.", "contents": "Amperometric and polarographic study of the SH-activity of MEPRIN (alpha-mercapto-propionylglycine). The SH-groups of alpha-mercapto-propionylglycine (MEPRIN) are remarkably stable in diluted solution either at room temperature or at 50 degrees C, even if storing takes place under air-bubbling. The SH-activity was measured by polarographic method and amperometric titration. Neutralization of the carboxyl group decreases the stability of the sulfhydryl groupings. Evaporation of neutralized solution leads to a 30--50 per cent decrease of SH-activity. Lyophilization reduces this loss by 10--15 per cent. Neutralization is best carried out in the absence of oxygen; in this case, 94 per cent of the sulfhydryl activity will persists, irrespective of the pH. The dissociation constant of MEPRIN-SH is pK' = 8.47. The SH-stability of the product is satisfactory when neutralized in nitrogen atmosphere to pH 3--5; a loss of only 5 per cent can be expected after storing in an oxygen-free 10(-3) molar solution for 144 hours. Between pH 6 and 8 this value is 31 per cent on the average, while at pH 9 it is more favorable again."}
{"id": "PMID:8948", "title": "Effects of phospholine iodide on the metabolites of the glycolytic, pentose phosphate and sorbitol pathways in the rabbit lens.", "content": "Steady-state concentrations of the key intermediates from the glycolytic, pentose phosphate, and sorbitol pathways as well as the pyridine nucleotides were measured from the lens after 0.25% phospholine iodide had been instilled into rabbits' eyes twice a day for 18 weeks. In the lenses of those rabbits which had received treatment in both eyes fructose-1,6-diphosphate and pyruvate levels were increased, whereas 6-phosphogluconate, sorbitol and alpha-glycer0phosphate concentrations were decreased. alpha-Ketoglutarate and concentrations and ratios of NAD+ and NADH did not show any changes. In contrast, NADPH and total NADP concentrations as well as the NADPH/NADP+ ratio were decreased, and therefore total NAD/total NADP ratio increased after treatment. It appears that instillation of long-acting 0.25% phospholine iodide into rabbits' eyes results in increased glycolytic activity in the lens in response to the increased energy demand, wheras the activities of other metabolic pathways are suppressed.", "contents": "Effects of phospholine iodide on the metabolites of the glycolytic, pentose phosphate and sorbitol pathways in the rabbit lens. Steady-state concentrations of the key intermediates from the glycolytic, pentose phosphate, and sorbitol pathways as well as the pyridine nucleotides were measured from the lens after 0.25% phospholine iodide had been instilled into rabbits' eyes twice a day for 18 weeks. In the lenses of those rabbits which had received treatment in both eyes fructose-1,6-diphosphate and pyruvate levels were increased, whereas 6-phosphogluconate, sorbitol and alpha-glycer0phosphate concentrations were decreased. alpha-Ketoglutarate and concentrations and ratios of NAD+ and NADH did not show any changes. In contrast, NADPH and total NADP concentrations as well as the NADPH/NADP+ ratio were decreased, and therefore total NAD/total NADP ratio increased after treatment. It appears that instillation of long-acting 0.25% phospholine iodide into rabbits' eyes results in increased glycolytic activity in the lens in response to the increased energy demand, wheras the activities of other metabolic pathways are suppressed."}
{"id": "PMID:8949", "title": "Clinical and cytogenetic studies in undescended testes.", "content": "168 boys and 2.5-16.8 years with unilateral or bilateral undescended testes or anorchia were studied. Retention was severe (canalicular or intraabdominal) in 1/4 and moderate in 3/4 of the cases. In unilateral retention, the volume of the scrotal testis was usually normal throughout childhood whereas pubertal testicular growth was delayed. In unilateral anorchia, the scrotal testis showed compensatory hypertrophy. In all age groups examined, the mean volume of the undescended testes was abnormally small. Undescended testes were accompanied by abnormalities of the epididymis in 3.6% of cases, of the ductus deferens in 7.8% and of the spermatic vessels in 8.3%. In anorchia such abnormalities were found regularly. Inguinal hernia accompanied 62.8% of the undescended testes and was most frequent in severe cases. Patients aged 8.0-9.9 years with unilateral undescended testis had advanced bone age. Cytogenic investigations of 167 patients revealed one case of Klinefelter's syndrome (47, XXY). Gonadotrophin treatment was tried in 50 patients and was succesful in 12. Surgical results were satisfactory in 86.1% of the operated testes.", "contents": "Clinical and cytogenetic studies in undescended testes. 168 boys and 2.5-16.8 years with unilateral or bilateral undescended testes or anorchia were studied. Retention was severe (canalicular or intraabdominal) in 1/4 and moderate in 3/4 of the cases. In unilateral retention, the volume of the scrotal testis was usually normal throughout childhood whereas pubertal testicular growth was delayed. In unilateral anorchia, the scrotal testis showed compensatory hypertrophy. In all age groups examined, the mean volume of the undescended testes was abnormally small. Undescended testes were accompanied by abnormalities of the epididymis in 3.6% of cases, of the ductus deferens in 7.8% and of the spermatic vessels in 8.3%. In anorchia such abnormalities were found regularly. Inguinal hernia accompanied 62.8% of the undescended testes and was most frequent in severe cases. Patients aged 8.0-9.9 years with unilateral undescended testis had advanced bone age. Cytogenic investigations of 167 patients revealed one case of Klinefelter's syndrome (47, XXY). Gonadotrophin treatment was tried in 50 patients and was succesful in 12. Surgical results were satisfactory in 86.1% of the operated testes."}
{"id": "PMID:8950", "title": "Endocrinological studies in undescended testes.", "content": "A cross-sectional study was carried out on 168 boys aged 2.5-16.8 years with unilateral or bilateral testicular maldescent. Urinary excretion of testosterone, delta4-androstenedione, LH and FSH was investigated. The results were related to chronological age, bone age and sexual maturation stage. Urinary testosterone excretion was elevated in unilateral and bilateral cases of undescended testis under 9 years of age. The pubertal increase of testosterone excretion seemed to be moderately delayed in the patients. In pubertal stage V the testosterone excretion was normal. The mean testosterone/androstenedione relationship was normal in all age groups up to 14.9 years and increased in patients above this age. After HCG stimulation, the testosterone excretion increased at all ages studied whereas the androstenedione excretion increased only in bilateral cases under 11 years of age. Urinary LH excretion was diminished in bilateral cases aged 6.0-7.9 years and elevated in unilateral cases in pubertal stage V. Urinary FSH excretion was normal below 8 years of age, moderately elevated in bilateral cases aged 8.0-11.9 years and increased in unilateral cases in pubertal stage V. Patients with bilateral anorchia in pubertal stage I, had normal basal testosterone and androstenedione excretion while the LH and FSH levels were increased. The findings in this study indicated that disturbances in the pituitary-gonadal function of cryptorchids might be operative from early childhood and throughout pubertal years.", "contents": "Endocrinological studies in undescended testes. A cross-sectional study was carried out on 168 boys aged 2.5-16.8 years with unilateral or bilateral testicular maldescent. Urinary excretion of testosterone, delta4-androstenedione, LH and FSH was investigated. The results were related to chronological age, bone age and sexual maturation stage. Urinary testosterone excretion was elevated in unilateral and bilateral cases of undescended testis under 9 years of age. The pubertal increase of testosterone excretion seemed to be moderately delayed in the patients. In pubertal stage V the testosterone excretion was normal. The mean testosterone/androstenedione relationship was normal in all age groups up to 14.9 years and increased in patients above this age. After HCG stimulation, the testosterone excretion increased at all ages studied whereas the androstenedione excretion increased only in bilateral cases under 11 years of age. Urinary LH excretion was diminished in bilateral cases aged 6.0-7.9 years and elevated in unilateral cases in pubertal stage V. Urinary FSH excretion was normal below 8 years of age, moderately elevated in bilateral cases aged 8.0-11.9 years and increased in unilateral cases in pubertal stage V. Patients with bilateral anorchia in pubertal stage I, had normal basal testosterone and androstenedione excretion while the LH and FSH levels were increased. The findings in this study indicated that disturbances in the pituitary-gonadal function of cryptorchids might be operative from early childhood and throughout pubertal years."}
{"id": "PMID:8951", "title": "Allo-aggression in chickens. II. Cellular expression of the AA gene products.", "content": "B1-anti-B2 and B2-anti-B1 allo-antisera were raised by i.v. immunization of homozygous B1/1 and B2/2 chickens, respectively, with B1/2 cells of the following sources: peripheral blood leucocytes (PBL), erythrocytes, thymus cells and bursa cells. Purified suspensions of these all produced anti-B allo-antibodies which could both haemagglutinate red blood cells and strongly inhibit the GVH reactivity of blood lymphocytes of the original donor type. Absorption studies of the sera using cells of the same four sources showed that they could all completely remove the GVH inhibitory antibodies. A fact of particular importance is that B-haplotype determined antigens which are common to erythrocytes and lymphocytes seem to include the gene products of the allo-aggression locus, as earlier defined (Simonsen 1975).", "contents": "Allo-aggression in chickens. II. Cellular expression of the AA gene products. B1-anti-B2 and B2-anti-B1 allo-antisera were raised by i.v. immunization of homozygous B1/1 and B2/2 chickens, respectively, with B1/2 cells of the following sources: peripheral blood leucocytes (PBL), erythrocytes, thymus cells and bursa cells. Purified suspensions of these all produced anti-B allo-antibodies which could both haemagglutinate red blood cells and strongly inhibit the GVH reactivity of blood lymphocytes of the original donor type. Absorption studies of the sera using cells of the same four sources showed that they could all completely remove the GVH inhibitory antibodies. A fact of particular importance is that B-haplotype determined antigens which are common to erythrocytes and lymphocytes seem to include the gene products of the allo-aggression locus, as earlier defined (Simonsen 1975)."}
{"id": "PMID:8947", "title": "[Epileptic headaches (author's transl)].", "content": "The author describes three observations characterized by the following similar features: 1. Children, between 2 and 9 years, suffering from attacks of sterotyped headaches. 2. EEG with bursts of high- voltage paroxysmal discharges, mainly during hyperventilation. 3. Efficiency of antiepileptic drugs contrary to antimigrainous treatment. These headaches are considered by the author as \"epileptic\", and this diagnosis is discussed.", "contents": "[Epileptic headaches (author's transl)]. The author describes three observations characterized by the following similar features: 1. Children, between 2 and 9 years, suffering from attacks of sterotyped headaches. 2. EEG with bursts of high- voltage paroxysmal discharges, mainly during hyperventilation. 3. Efficiency of antiepileptic drugs contrary to antimigrainous treatment. These headaches are considered by the author as \"epileptic\", and this diagnosis is discussed."}
{"id": "PMID:8955", "title": "Influence of pH and pCO2 on alpha-receptor mediated contraction in brain vessels.", "content": "The response of isolated brain vessels to various pH levels or carbon dioxide tensions was analyzed. Reduction of the pH induced a slight relaxation of the vessel, whereas an increase in the pH produced a slight contraction. These effects were markedly exaggerated when the alpha-adrenergic receptors in the vascular wall were activated by noradrenaline. During these conditions the contractile response to noradrenaline was reduced by about 40% at a pH of 7.01, while, on the other hand, the response was enhanced 3-fold at a pH of 7.80. Variations in carbon dioxide  tension of the buffer solution between 16 mmHg and 64 mmHg produced no consistent change, provided the pH remained constant. The results indicate that an interaction between the perivascular pH and the adrenergic alpha-receptor mediated contraction in brain vessels may occur.", "contents": "Influence of pH and pCO2 on alpha-receptor mediated contraction in brain vessels. The response of isolated brain vessels to various pH levels or carbon dioxide tensions was analyzed. Reduction of the pH induced a slight relaxation of the vessel, whereas an increase in the pH produced a slight contraction. These effects were markedly exaggerated when the alpha-adrenergic receptors in the vascular wall were activated by noradrenaline. During these conditions the contractile response to noradrenaline was reduced by about 40% at a pH of 7.01, while, on the other hand, the response was enhanced 3-fold at a pH of 7.80. Variations in carbon dioxide  tension of the buffer solution between 16 mmHg and 64 mmHg produced no consistent change, provided the pH remained constant. The results indicate that an interaction between the perivascular pH and the adrenergic alpha-receptor mediated contraction in brain vessels may occur."}
{"id": "PMID:8956", "title": "[Logical analysis of the respective influence of 3 experimental variables using a diagram by L. Carroll. Application of this method to a clinical trial of 2 forms of Noveril].", "content": "The analysis of the results gathered in a double-blind randomized cross-over clinical trial of dibenzepine was systematized in order to evidence the relation existing between the experimental variables and the effects measured. The suggested method of analysis is based on logic and makes profit of a diagram by Carroll. This method seemingly permits rigourous and clear conclusions.", "contents": "[Logical analysis of the respective influence of 3 experimental variables using a diagram by L. Carroll. Application of this method to a clinical trial of 2 forms of Noveril]. The analysis of the results gathered in a double-blind randomized cross-over clinical trial of dibenzepine was systematized in order to evidence the relation existing between the experimental variables and the effects measured. The suggested method of analysis is based on logic and makes profit of a diagram by Carroll. This method seemingly permits rigourous and clear conclusions."}
{"id": "PMID:8958", "title": "Effects of chlorthalidone on serum and total body potassium in hypertensive patients.", "content": "Total body potassium has been estimated in 26 hypertensive patients who were hypokalaemic as a result of long-term chlorthalidone treatment (mean 20.5 months), while they were on chlorthalidone and 4 weeks after this had been discontinued. The mean difference amounted to only 95 mEq (not significant). In 6 additional patients not previously treated with chlorthalidone, serial total body potassium estimations revealed a mean potassium deficiency of 245 mEq after 33 days and of 106 mEq after 100 days. These results suggest that the mechanism causing the initial potassium loss is partly reversed or compensated later on. In patients with uncomplicated hypertension, no significant potassium deficiency was detected during long-term treatment. Eighteen of our patients received 39 mEq potassium chloride supplements daily for 4 weeks; this caused a mean rise in serum potassium from 3.23 mEq/l to 3.38 mEq/l (not significant). Total body potassium did not change at all. We conclude that potassium chloride supplements are not an effective treatment of hypokalaemia in this condition. Correction of the extracellular pH by ammonium chloride in 6 patients on chlorthalidone, who demonstrated a slight metabolic alkalosis, gave rise to a mean increase in plasma potassium from 2.78 mEq/l to 2.96 mEq/l (not significant). The hypokalaemia in hypertensive patients on long-term chlorthalidone treatment cannot be explained by either a potassium deficiency or the change in extracellular pH.", "contents": "Effects of chlorthalidone on serum and total body potassium in hypertensive patients. Total body potassium has been estimated in 26 hypertensive patients who were hypokalaemic as a result of long-term chlorthalidone treatment (mean 20.5 months), while they were on chlorthalidone and 4 weeks after this had been discontinued. The mean difference amounted to only 95 mEq (not significant). In 6 additional patients not previously treated with chlorthalidone, serial total body potassium estimations revealed a mean potassium deficiency of 245 mEq after 33 days and of 106 mEq after 100 days. These results suggest that the mechanism causing the initial potassium loss is partly reversed or compensated later on. In patients with uncomplicated hypertension, no significant potassium deficiency was detected during long-term treatment. Eighteen of our patients received 39 mEq potassium chloride supplements daily for 4 weeks; this caused a mean rise in serum potassium from 3.23 mEq/l to 3.38 mEq/l (not significant). Total body potassium did not change at all. We conclude that potassium chloride supplements are not an effective treatment of hypokalaemia in this condition. Correction of the extracellular pH by ammonium chloride in 6 patients on chlorthalidone, who demonstrated a slight metabolic alkalosis, gave rise to a mean increase in plasma potassium from 2.78 mEq/l to 2.96 mEq/l (not significant). The hypokalaemia in hypertensive patients on long-term chlorthalidone treatment cannot be explained by either a potassium deficiency or the change in extracellular pH."}
{"id": "PMID:8959", "title": "Liver enzymes in alcohol-discordant twins.", "content": "Seventy moderately alcohol-discordant male twin pairs have been investigated with respect to some liver enzymes. No differences were found as regards S-ALAT, while significantly higher enzyme levels were demonstrated for S-ASAT, S-ALP and S-GT among the high alcohol consumers compared to their low consuming co-twins. Especially S-GT was found to be a valuable and sensitive test in the detection of even a moderate alcohol intake in working and socially well adapted subjects. These results were obtained in a subject group in which the influence of genetic factors was kept to a minimum.", "contents": "Liver enzymes in alcohol-discordant twins. Seventy moderately alcohol-discordant male twin pairs have been investigated with respect to some liver enzymes. No differences were found as regards S-ALAT, while significantly higher enzyme levels were demonstrated for S-ASAT, S-ALP and S-GT among the high alcohol consumers compared to their low consuming co-twins. Especially S-GT was found to be a valuable and sensitive test in the detection of even a moderate alcohol intake in working and socially well adapted subjects. These results were obtained in a subject group in which the influence of genetic factors was kept to a minimum."}
{"id": "PMID:8957", "title": "[Ulcerative rectocolitis. Somatic aspects (author's transl)].", "content": "Regional enteritis (Crohn's disease) and ulcerative rectocolitis, both \"non specific inflammatory diseases of the bowel\", might be diseases with a common etiology but with clinical features corresponding to a different tissular response to a noxious factor. Both diseases are however characterized by distinct clinical, radiological, histological peculiarities; evolution also is different, as appears from the rarity of malignant degeneration in Crohn's disease and its frequence in ulcerative colitis; a psychological support seems to be classical in ulcerative colitis but is on the contrary unusual in regional ileitis. Besides the interference of psychological factors in the outbreak of an ulcerative colitis, besides the infectious and genetic theories, the immunological theory appears as one of the most interesting and promising. In a significant percentage of cases of ulcerative colitis, anticolon antibodies are evidenced, which exhibit a crossed reaction with bacterial antigens, especially with those of Escherichia coli 014. Besides this humoral immunity a cellular immunity exists also: lymphocytes of patients with ulcerative colitis behave as a toxic agent towards colic tissue cultures; this cytotoxicity parallels the course of the disease and provides an explanation for the sometimes dramatic therapeutic effects observed after administration of immunosuppressive drugs and antilymphocytic serum. Moreover, colic antigen can block this cytotoxicity; the immunologically active portion of this antigen may be isolated and its administration in patients with ulcerative colitis may perhaps induce a specific immunosuppression and influence the evolution of the disease.", "contents": "[Ulcerative rectocolitis. Somatic aspects (author's transl)]. Regional enteritis (Crohn's disease) and ulcerative rectocolitis, both \"non specific inflammatory diseases of the bowel\", might be diseases with a common etiology but with clinical features corresponding to a different tissular response to a noxious factor. Both diseases are however characterized by distinct clinical, radiological, histological peculiarities; evolution also is different, as appears from the rarity of malignant degeneration in Crohn's disease and its frequence in ulcerative colitis; a psychological support seems to be classical in ulcerative colitis but is on the contrary unusual in regional ileitis. Besides the interference of psychological factors in the outbreak of an ulcerative colitis, besides the infectious and genetic theories, the immunological theory appears as one of the most interesting and promising. In a significant percentage of cases of ulcerative colitis, anticolon antibodies are evidenced, which exhibit a crossed reaction with bacterial antigens, especially with those of Escherichia coli 014. Besides this humoral immunity a cellular immunity exists also: lymphocytes of patients with ulcerative colitis behave as a toxic agent towards colic tissue cultures; this cytotoxicity parallels the course of the disease and provides an explanation for the sometimes dramatic therapeutic effects observed after administration of immunosuppressive drugs and antilymphocytic serum. Moreover, colic antigen can block this cytotoxicity; the immunologically active portion of this antigen may be isolated and its administration in patients with ulcerative colitis may perhaps induce a specific immunosuppression and influence the evolution of the disease."}
{"id": "PMID:8960", "title": "On the nature of brain stem disorders in severe head injured patients. II. A study on caloric vestibular reactions and neurotransmitter treatment.", "content": "The results of electro-oculographic recordings made after caloric vestibular stimulation (C.O.G.) in severe head injured patients are discussed. It was found that: 1. The C.O.G. correlates with the state of consciousness of the patients. 2. The rate of improvement of the C.O.G. correlates with the rate of the clinical improvement. 3. A prediction of the duration of unconsciousness can be made by repeated C.O.G. scores as well as by repeated scoring of the clinical state. 4. In all patients a paradoxical response is present except in those who have regained clear consciousness and in those persisting in a vegetative state, so the presence of a paradoxical response indicates the possibility of further improvement. It was supposed that in patients with a paradoxical response a functional brain dysfunction was present, which was at least partly caused by disturbed neurotransmitter metabolism. Therapeutic trials with L-DOPA and physostigmine were successful in patients with a paradoxical response, but without any result in those without this phenomenon. The responses to L-DOPA and to physostigmine are related respectively to motor pattern and to verbal or non-verbal communication.", "contents": "On the nature of brain stem disorders in severe head injured patients. II. A study on caloric vestibular reactions and neurotransmitter treatment. The results of electro-oculographic recordings made after caloric vestibular stimulation (C.O.G.) in severe head injured patients are discussed. It was found that: 1. The C.O.G. correlates with the state of consciousness of the patients. 2. The rate of improvement of the C.O.G. correlates with the rate of the clinical improvement. 3. A prediction of the duration of unconsciousness can be made by repeated C.O.G. scores as well as by repeated scoring of the clinical state. 4. In all patients a paradoxical response is present except in those who have regained clear consciousness and in those persisting in a vegetative state, so the presence of a paradoxical response indicates the possibility of further improvement. It was supposed that in patients with a paradoxical response a functional brain dysfunction was present, which was at least partly caused by disturbed neurotransmitter metabolism. Therapeutic trials with L-DOPA and physostigmine were successful in patients with a paradoxical response, but without any result in those without this phenomenon. The responses to L-DOPA and to physostigmine are related respectively to motor pattern and to verbal or non-verbal communication."}
{"id": "PMID:8961", "title": "Adrenergic blockade in subarachnoid haemorrhage.", "content": "Over the last 15 years progressive interest has developed in the relationship between subarachnoid haemorrhage, sympathetic nervous system over-activity and the genesis of cerebral artery spasm. Following on from earlier work, vide infra, suggesting that adrenergic blockade might influence the course and prognosis of patients with subarachnoid haemorrhage, two double blind trials have recently been completed in Southampton. The first trial attempted to establish whether or not a single intracarotid injection of phenoxybenzamine improved the mortality and late morbidity of patients with subarachnoid haemorrhage. Results suggested that it did not. The second trial, comprising two groups of 50 patients each, attempted to assess the influence of prolonged treatment with propranolol on the course and prognosis of these subarachnoid haemorrhage patients. Early results suggest that, as with the alpha-blocker, the mortality and severe morbidity was not improved by beta-adrenergic blockade.", "contents": "Adrenergic blockade in subarachnoid haemorrhage. Over the last 15 years progressive interest has developed in the relationship between subarachnoid haemorrhage, sympathetic nervous system over-activity and the genesis of cerebral artery spasm. Following on from earlier work, vide infra, suggesting that adrenergic blockade might influence the course and prognosis of patients with subarachnoid haemorrhage, two double blind trials have recently been completed in Southampton. The first trial attempted to establish whether or not a single intracarotid injection of phenoxybenzamine improved the mortality and late morbidity of patients with subarachnoid haemorrhage. Results suggested that it did not. The second trial, comprising two groups of 50 patients each, attempted to assess the influence of prolonged treatment with propranolol on the course and prognosis of these subarachnoid haemorrhage patients. Early results suggest that, as with the alpha-blocker, the mortality and severe morbidity was not improved by beta-adrenergic blockade."}
{"id": "PMID:8964", "title": "Comparison of function of the distal base between myoglobin and peroxidase.", "content": "The heme-linked protonation of a ferrous horseradish peroxidase is assigned to a distal amino acid residue. The conclusion is drawn from analyses of reactions that involve the protonation. Unfortunately it is difficult to apply it to the myoglobin case because no reaction has been found which is coupled with the protonation of the distal histidine. It is therefore of special interest to note that the pK value of 5.7 has been assigned to the distal histidine of metmyoglobin from binding kinetics with ligands20). It is well known that the reaction with hydrogen peroxide is quite different for the two types of hemoproteins. The distal base may be associated with the stabilization of the primary compound with hydrogen peroxide and also another amino acid residue may serve as a nucleophile for the stabilization of the pi-cation radical of porphyrin in the case if peroxidases. Numerous papers have dealt with heme substitution, heme linked protonation and reactions of hemoproteins related to the present subject. In this short paper, however, the discussion has mostly centered around the data obtained recently in our laboratory.", "contents": "Comparison of function of the distal base between myoglobin and peroxidase. The heme-linked protonation of a ferrous horseradish peroxidase is assigned to a distal amino acid residue. The conclusion is drawn from analyses of reactions that involve the protonation. Unfortunately it is difficult to apply it to the myoglobin case because no reaction has been found which is coupled with the protonation of the distal histidine. It is therefore of special interest to note that the pK value of 5.7 has been assigned to the distal histidine of metmyoglobin from binding kinetics with ligands20). It is well known that the reaction with hydrogen peroxide is quite different for the two types of hemoproteins. The distal base may be associated with the stabilization of the primary compound with hydrogen peroxide and also another amino acid residue may serve as a nucleophile for the stabilization of the pi-cation radical of porphyrin in the case if peroxidases. Numerous papers have dealt with heme substitution, heme linked protonation and reactions of hemoproteins related to the present subject. In this short paper, however, the discussion has mostly centered around the data obtained recently in our laboratory."}
{"id": "PMID:8969", "title": "Biological effects of cyclosporin A: a new antilymphocytic agent.", "content": "The fungus metabolite cyclosporin A is a small peptide acting as a novel antilymphocytic agent. It strongly depressed appearance of both direct and indirect plaque-forming cells and produced a clear dose-dependent inhibition of haemagglutinin formation in mice upon oral administration. Skin graft rejection in mice and graft-versus-host disease in mice and rats were considerably delayed by cycloporin A which also prevented the occurrence of paralysis in rats with experimental allergic encephalomyelitis. This compound was not only highly effective in preventing development of Freund's adjuvant arthritis, but in addition improved the symptoms in rats with established arthritis, although it is inactive in acute inflammation. This new agent contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity. Experimental evidence suggests that cyclosporin A, rather than being cytostatic or lympholytic, affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell.", "contents": "Biological effects of cyclosporin A: a new antilymphocytic agent. The fungus metabolite cyclosporin A is a small peptide acting as a novel antilymphocytic agent. It strongly depressed appearance of both direct and indirect plaque-forming cells and produced a clear dose-dependent inhibition of haemagglutinin formation in mice upon oral administration. Skin graft rejection in mice and graft-versus-host disease in mice and rats were considerably delayed by cycloporin A which also prevented the occurrence of paralysis in rats with experimental allergic encephalomyelitis. This compound was not only highly effective in preventing development of Freund's adjuvant arthritis, but in addition improved the symptoms in rats with established arthritis, although it is inactive in acute inflammation. This new agent contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity. Experimental evidence suggests that cyclosporin A, rather than being cytostatic or lympholytic, affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell."}
{"id": "PMID:8972", "title": "Ultrastructural comparison of the midgut epithelia of fleas with different feeding behavior patterns (Xenopsylla cheopis, Echidnophaga gallinacea, Tunga penetrans, Siphonaptera, Pulicidae).", "content": "This morphological study describes the ultrastructure of the midgut of three flea species, including temporary parasitic fleas (both sexes of Xenopsylla cheopis, males and immature females of Echidnophaga gallinacea and Tunga penetrans) and stationary parasitic fleas (mature females of E. gallinacea and T. penetrans). (1) Three cell types (a,b,c) constitute the midgut epithelium, each appearing in a characteristic and constant frequency along the whole midgut, a) The functional digestive cells form the main part of the epithelium as one layer of cylindric cells. Nuclear volume and nucleus/cytoplasm ratio have been estimated (with morphometric methods) to be the same in both sexes of E. gallinacea and T. penetrans. b) Some single regenerative cells or nests, containing 5-10 cells per section plane, lay at the base of the epithelium (2-3 cells or nests per cross section of a midgut). c) Secretory cells are characterized by their opaque cytoplasm which contains electron-dense vesicles. They have few microvilli and no basal labyrinth and are placed between digestive cells only as single cells (1-2 per cross section of a midgut). (2) After the first bloodmeal some ultrastructural changes occur in the midgut of all fleas. These changes are interpreted as a structural reflection of metabolic processes such as secretion of digestive enzymes, resorption, storage and transport of digested nutrients, and synthesis of digestive enzymes. (3) More conspicious changes occur in the midgut of the stationary parasitic and maturing females of E. gallinacea and T. penetrans. The nuclear volumes of the digestive cells reach the two-fold and eight-fold value, respectively. The nucleus/cytoplasm ratio decreases by half. The corresponding cytoplasmic growth of each cell is reflected in an enlargement of the whole midgut. The digestive cells form long apical cell extensions. The nucleus, basal labyrinth, rer, and golgi complex all change their morphology, and this can be interpreted as the result of a higher level of metabolic activity than during the first bloodmeal. (4) The midgut of the oviparous female of T. penetrans undergoes a process of compensatory hypertrophy which consists in the cellular hypertrophy of each digestive cell and in an extensive proliferation of the regenerative cells. A unique structure, called 'nuclear halo' appears within the process of cellular hypertrophy. This structure consists of a layer of 70-100 A thick filaments along the periphery of the nucleus. The nuclear halo contains few ribosomes and is screened from the cytoplasm by an rer cisterna. The filaments may contain RNA molecules which are on their way to the cytoplasm. It has been demonstrated that the structure of the midgut epithelium is influenced by the nutritive and parasitic behavior of the flea. The stationary and oviparous E. gallinacea and T. penetrans reveal an extensive and irreversible change of their midgut epithelium.", "contents": "Ultrastructural comparison of the midgut epithelia of fleas with different feeding behavior patterns (Xenopsylla cheopis, Echidnophaga gallinacea, Tunga penetrans, Siphonaptera, Pulicidae). This morphological study describes the ultrastructure of the midgut of three flea species, including temporary parasitic fleas (both sexes of Xenopsylla cheopis, males and immature females of Echidnophaga gallinacea and Tunga penetrans) and stationary parasitic fleas (mature females of E. gallinacea and T. penetrans). (1) Three cell types (a,b,c) constitute the midgut epithelium, each appearing in a characteristic and constant frequency along the whole midgut, a) The functional digestive cells form the main part of the epithelium as one layer of cylindric cells. Nuclear volume and nucleus/cytoplasm ratio have been estimated (with morphometric methods) to be the same in both sexes of E. gallinacea and T. penetrans. b) Some single regenerative cells or nests, containing 5-10 cells per section plane, lay at the base of the epithelium (2-3 cells or nests per cross section of a midgut). c) Secretory cells are characterized by their opaque cytoplasm which contains electron-dense vesicles. They have few microvilli and no basal labyrinth and are placed between digestive cells only as single cells (1-2 per cross section of a midgut). (2) After the first bloodmeal some ultrastructural changes occur in the midgut of all fleas. These changes are interpreted as a structural reflection of metabolic processes such as secretion of digestive enzymes, resorption, storage and transport of digested nutrients, and synthesis of digestive enzymes. (3) More conspicious changes occur in the midgut of the stationary parasitic and maturing females of E. gallinacea and T. penetrans. The nuclear volumes of the digestive cells reach the two-fold and eight-fold value, respectively. The nucleus/cytoplasm ratio decreases by half. The corresponding cytoplasmic growth of each cell is reflected in an enlargement of the whole midgut. The digestive cells form long apical cell extensions. The nucleus, basal labyrinth, rer, and golgi complex all change their morphology, and this can be interpreted as the result of a higher level of metabolic activity than during the first bloodmeal. (4) The midgut of the oviparous female of T. penetrans undergoes a process of compensatory hypertrophy which consists in the cellular hypertrophy of each digestive cell and in an extensive proliferation of the regenerative cells. A unique structure, called 'nuclear halo' appears within the process of cellular hypertrophy. This structure consists of a layer of 70-100 A thick filaments along the periphery of the nucleus. The nuclear halo contains few ribosomes and is screened from the cytoplasm by an rer cisterna. The filaments may contain RNA molecules which are on their way to the cytoplasm. It has been demonstrated that the structure of the midgut epithelium is influenced by the nutritive and parasitic behavior of the flea. The stationary and oviparous E. gallinacea and T. penetrans reveal an extensive and irreversible change of their midgut epithelium."}
{"id": "PMID:8973", "title": "Nutrition of Glossina morsitans: metabolism of U-14C threonine during pregnancy.", "content": "Following injection of U-14C threonine into the haemolymph of adult female Glossina morsitans during late pregnancy, radioactivity was detected in the postparturient female and in its offspring, in threonine, lipids, and a range of non-essential amino acids. The level of radioactivity recovered from the larva was higher than that remaining in the injected adult, and the radioactivity recovered was considerably higher in the amino acid than in the lipid fraction. Administration of labelled threonine into maternal haemolymph on each of the first 8 days of the 9-10 day long pregnancy cycle was followed 24 h later by measurement of radioactivity in the developing o\u00f6cyte and in the intra-uterine progeny. The patterns of nutrient uptake are discussed in relation to vitellogenesis in the o\u00f6cyte and to growth of the larva. Analysis of the expired carbon dioxide and excreta was carried out 24 h after maternal injection of labelled threonine on the first or eighth day of pregnancy. Carbon dioxide and excreta from females in early pregnancy showed significantly higher radioactivity than those from females in late pregnancy. In both cases, radioactivity in the amino acid fraction from the excreta was extremely small and about 95% of the total activity was in uric acid. These results are discussed in terms of the utilization of threonine in relation to the metabolic demands for various nutriments by the pregnant female.", "contents": "Nutrition of Glossina morsitans: metabolism of U-14C threonine during pregnancy. Following injection of U-14C threonine into the haemolymph of adult female Glossina morsitans during late pregnancy, radioactivity was detected in the postparturient female and in its offspring, in threonine, lipids, and a range of non-essential amino acids. The level of radioactivity recovered from the larva was higher than that remaining in the injected adult, and the radioactivity recovered was considerably higher in the amino acid than in the lipid fraction. Administration of labelled threonine into maternal haemolymph on each of the first 8 days of the 9-10 day long pregnancy cycle was followed 24 h later by measurement of radioactivity in the developing o\u00f6cyte and in the intra-uterine progeny. The patterns of nutrient uptake are discussed in relation to vitellogenesis in the o\u00f6cyte and to growth of the larva. Analysis of the expired carbon dioxide and excreta was carried out 24 h after maternal injection of labelled threonine on the first or eighth day of pregnancy. Carbon dioxide and excreta from females in early pregnancy showed significantly higher radioactivity than those from females in late pregnancy. In both cases, radioactivity in the amino acid fraction from the excreta was extremely small and about 95% of the total activity was in uric acid. These results are discussed in terms of the utilization of threonine in relation to the metabolic demands for various nutriments by the pregnant female."}
{"id": "PMID:8974", "title": "Development of Trypanosoma (Trypanozoon) brucei in Glossina morsitans inoculated into the tsetse haemocoel.", "content": "Classically, infective development of Trypanosoma (Trypanozoon) brucei in tsetse flies is thought to take the route crop-midgut-hindgut proventriculus-hypopharynx-salivary gland, where the parasites reach their infective phase. It has been shown experimentally that T. (T.) brucei is capable of developing up to the infective stage in G. morsitans following inoculation of bloodstream form trypanosomes into the haemocoel. The rabbit on which flies were maintained became infected 18 days after exposure to the bite of experimentally inoculated flies. The possibility that T. (T.) brucei may be transmitted cyclically from tsetse flies to a mammalian host without necessarily following the classical, prescribed route is discussed. Apart from the normal longitudinal binary fission, various modes of multiplication were observed among trypanosomes in the haemocoel, modes which have not been observed previously in the tsetse fly.", "contents": "Development of Trypanosoma (Trypanozoon) brucei in Glossina morsitans inoculated into the tsetse haemocoel. Classically, infective development of Trypanosoma (Trypanozoon) brucei in tsetse flies is thought to take the route crop-midgut-hindgut proventriculus-hypopharynx-salivary gland, where the parasites reach their infective phase. It has been shown experimentally that T. (T.) brucei is capable of developing up to the infective stage in G. morsitans following inoculation of bloodstream form trypanosomes into the haemocoel. The rabbit on which flies were maintained became infected 18 days after exposure to the bite of experimentally inoculated flies. The possibility that T. (T.) brucei may be transmitted cyclically from tsetse flies to a mammalian host without necessarily following the classical, prescribed route is discussed. Apart from the normal longitudinal binary fission, various modes of multiplication were observed among trypanosomes in the haemocoel, modes which have not been observed previously in the tsetse fly."}
{"id": "PMID:8975", "title": "Filaments of Trypanosoma brucei: some notes on differences in origin and structure in two strains of Trypanosoma (Trypanozoon) brucei rhodesiense.", "content": "Filaments attached to trypanosomes of two strains of T. (T.) brucei were studied by electron microscopy and two distinct types identified: short-thick and long-thin. The former are associated with stumpy trypanosomes and are secretions, via the flagellar pocket, which originate in the area of the Golgi complex, during the infection of the host. They are referred to as 'secretory filaments'. Their diameter is 0.09 to 0.14 mum. The long-thin filaments are associated with slender forms of trypanosome in various artificial situations; those shown by negative staining are believed to be cytoplasmic extrusions from the anatomically weak extremities of the parasite and are referred to as 'plasmanemes'. Their diameter is 0.06 mum. Both types appear to maintain their structure without the aid of the normal type of unit membrane as myelin formations.", "contents": "Filaments of Trypanosoma brucei: some notes on differences in origin and structure in two strains of Trypanosoma (Trypanozoon) brucei rhodesiense. Filaments attached to trypanosomes of two strains of T. (T.) brucei were studied by electron microscopy and two distinct types identified: short-thick and long-thin. The former are associated with stumpy trypanosomes and are secretions, via the flagellar pocket, which originate in the area of the Golgi complex, during the infection of the host. They are referred to as 'secretory filaments'. Their diameter is 0.09 to 0.14 mum. The long-thin filaments are associated with slender forms of trypanosome in various artificial situations; those shown by negative staining are believed to be cytoplasmic extrusions from the anatomically weak extremities of the parasite and are referred to as 'plasmanemes'. Their diameter is 0.06 mum. Both types appear to maintain their structure without the aid of the normal type of unit membrane as myelin formations."}
{"id": "PMID:8976", "title": "[New species of Microsporidia, parasite of Myriapoda-Diplopoda of South Dahomey].", "content": "A new microsporidian parasitic in Myriapoda-Diplopoda of Sud-Dahomey (Habrodesmus falx Cook & Oxydesmus granulosus Palisot de Beauvois) is described by photonic microscopy. It can be recognized by its thick-enveloped pansporoblasts yielding from 30 to 66 elongate and ovoid spores measuring 4,8 mum in length and 2,2 mum in diameter. The spore is uninucleate. This microsporidian forms cysts in the anterior part of the host affecting the musculature of the digestive tract, the adipose tissue and segmentary muscles. However, it appears necessary to study this parasite again by means of electron microscopy for a better understanding of its life-cycle and in order to place it in the Microsporidian taxonomy.", "contents": "[New species of Microsporidia, parasite of Myriapoda-Diplopoda of South Dahomey]. A new microsporidian parasitic in Myriapoda-Diplopoda of Sud-Dahomey (Habrodesmus falx Cook & Oxydesmus granulosus Palisot de Beauvois) is described by photonic microscopy. It can be recognized by its thick-enveloped pansporoblasts yielding from 30 to 66 elongate and ovoid spores measuring 4,8 mum in length and 2,2 mum in diameter. The spore is uninucleate. This microsporidian forms cysts in the anterior part of the host affecting the musculature of the digestive tract, the adipose tissue and segmentary muscles. However, it appears necessary to study this parasite again by means of electron microscopy for a better understanding of its life-cycle and in order to place it in the Microsporidian taxonomy."}
{"id": "PMID:8977", "title": "[General survey of the present distribution of helminths in Iran and comparison with those of past years].", "content": "In this paper the literature on helminthiasis in Iran is reviewed and the distribution, prevalence and intensity of infections caused by helminths are discussed. A comparison of prevalence and intensity of infections was accomplished in the recent 10 years by the author. Hookworm infections are found mostly in the north along the Caspian sea, but its prevalence is declining. Trichostrongylus are found in Iran with a high prevalence in central country. Schistosoma haematobium is found in one Province in the south, but its prevalence is declining because of large scale control activities. The Guinea worm rarely occurs in Iran. The prevalence of Fasciola hepatica is high among livestock and is occasionally found in man. Taenia saginata is found in most parts of Iran. Taenia solium is seldom found in animals with a prevalence of 0.03%. Trichinella spiralis is infrequently found in animals. Dioctophyma renale is found in straying dogs in the north or Iran, the percentage is 13-35%. Oxyuriasis is widespread among children.", "contents": "[General survey of the present distribution of helminths in Iran and comparison with those of past years]. In this paper the literature on helminthiasis in Iran is reviewed and the distribution, prevalence and intensity of infections caused by helminths are discussed. A comparison of prevalence and intensity of infections was accomplished in the recent 10 years by the author. Hookworm infections are found mostly in the north along the Caspian sea, but its prevalence is declining. Trichostrongylus are found in Iran with a high prevalence in central country. Schistosoma haematobium is found in one Province in the south, but its prevalence is declining because of large scale control activities. The Guinea worm rarely occurs in Iran. The prevalence of Fasciola hepatica is high among livestock and is occasionally found in man. Taenia saginata is found in most parts of Iran. Taenia solium is seldom found in animals with a prevalence of 0.03%. Trichinella spiralis is infrequently found in animals. Dioctophyma renale is found in straying dogs in the north or Iran, the percentage is 13-35%. Oxyuriasis is widespread among children."}
{"id": "PMID:8980", "title": "Otitis media of infancy and early childhood. A double-blind study of four treatment regimens.", "content": "A double-blind, randomized trial of four antimicrobial regimens was conducted in 383 infants and children with acute otitis media. The drugs used were penicillin V, amoxicillin trihydrate, erythromycin estolate, and erythromycin estolate with trisulfapyrimidines. Aspiration of middle ear fluid for culture was done before treatment and repeated during treatment if fluid persisted. Etiologic bacteria were most commonly pneumococci (31%) or Haemophilus sp (22%), and an additional 5% of patients had both organisms. Amoxicillin was the most effective in promoting initial response in pneumococcal infection. For Haemophilus infections, the cure rates with amoxicillin and the erythromycin-trisulfapyrimidines mixture were significantly better than with the other two regimens, and serous otitis did not occur during the follow-up period; however, new episodes of otitis were comparable in the four groups. Amoxicillin and the erythromycin estolate-trisulfapyrimidines combination appear to be somewhat more effective than penicillin V or erythromycin estolate.", "contents": "Otitis media of infancy and early childhood. A double-blind study of four treatment regimens. A double-blind, randomized trial of four antimicrobial regimens was conducted in 383 infants and children with acute otitis media. The drugs used were penicillin V, amoxicillin trihydrate, erythromycin estolate, and erythromycin estolate with trisulfapyrimidines. Aspiration of middle ear fluid for culture was done before treatment and repeated during treatment if fluid persisted. Etiologic bacteria were most commonly pneumococci (31%) or Haemophilus sp (22%), and an additional 5% of patients had both organisms. Amoxicillin was the most effective in promoting initial response in pneumococcal infection. For Haemophilus infections, the cure rates with amoxicillin and the erythromycin-trisulfapyrimidines mixture were significantly better than with the other two regimens, and serous otitis did not occur during the follow-up period; however, new episodes of otitis were comparable in the four groups. Amoxicillin and the erythromycin estolate-trisulfapyrimidines combination appear to be somewhat more effective than penicillin V or erythromycin estolate."}
{"id": "PMID:8985", "title": "Influences on role expansion.", "content": "Several factors are influencing role expansion for registered nurses, among them the shortage of primary care physicians, the federal government, the physician's assistant movement, the growing complexity of acute hospital care, educational reform, and the women's liberation movement. As state licensure statutes are revised to allow for role expansion, the changing laws themselves become a factor supporting the movement.", "contents": "Influences on role expansion. Several factors are influencing role expansion for registered nurses, among them the shortage of primary care physicians, the federal government, the physician's assistant movement, the growing complexity of acute hospital care, educational reform, and the women's liberation movement. As state licensure statutes are revised to allow for role expansion, the changing laws themselves become a factor supporting the movement."}
{"id": "PMID:8986", "title": "Maternal and fetal effects of lumbar epidural analgesia for labor and delivery in patients with gestational hypertension.", "content": "The effects of continuous lumbar epidural analgesia for labor and delivery were studied in 20 women with gestational hypertension. Maternal hemodynamics, renal function, acid-base, and blood gas findings were examined together with newborn APgar scores and umbilical vessel blood gas and acid-base values. Minimal change occurred in maternal renal function and hemodynamics. Maternal and bewborn aicd-base and blood gas findings were comparable to those  of normotensive control subjects also receiving epidural analgesia. Apgar scores in both groups of subjects wer good. Continuous epidural analgesia is recommended as a useful form of therapy in the management of labor and delivery in women with gestational hypertension.", "contents": "Maternal and fetal effects of lumbar epidural analgesia for labor and delivery in patients with gestational hypertension. The effects of continuous lumbar epidural analgesia for labor and delivery were studied in 20 women with gestational hypertension. Maternal hemodynamics, renal function, acid-base, and blood gas findings were examined together with newborn APgar scores and umbilical vessel blood gas and acid-base values. Minimal change occurred in maternal renal function and hemodynamics. Maternal and bewborn aicd-base and blood gas findings were comparable to those  of normotensive control subjects also receiving epidural analgesia. Apgar scores in both groups of subjects wer good. Continuous epidural analgesia is recommended as a useful form of therapy in the management of labor and delivery in women with gestational hypertension."}
{"id": "PMID:8987", "title": "Circulatory response to atropine in sheep fetus.", "content": "Atropine was given to the semichronic sheep fetus intravenously. Fetal heart rate, fetal perfusion pressure, and carotid blood flow increased. Cerebral blood flow was measured with the radioactive microsphere technique. Atropine was capable of increasing the cerebral blood flow. Elevation of carbon dioxide also caused an increase in cerebral blood flow, adding to the effect of atropine.", "contents": "Circulatory response to atropine in sheep fetus. Atropine was given to the semichronic sheep fetus intravenously. Fetal heart rate, fetal perfusion pressure, and carotid blood flow increased. Cerebral blood flow was measured with the radioactive microsphere technique. Atropine was capable of increasing the cerebral blood flow. Elevation of carbon dioxide also caused an increase in cerebral blood flow, adding to the effect of atropine."}
{"id": "PMID:8988", "title": "Nutritional deficiency, immunologic function, and disease.", "content": "Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed.", "contents": "Nutritional deficiency, immunologic function, and disease. Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed."}
{"id": "PMID:8989", "title": "Acid-base changes in milk and blood of rats in acidosis and alkalosis.", "content": "Lactating white rats (Rattus norvegicus) were subjected to metabolic and respiratory acidosis and metabolic alkalosis. Before and during the various treatments, the acid-base status of heart blood and milk was determined. Acute metabolic acidosis lowered the pH of plasma and milk; Pco(2) and bicarbonate concentrations in plasma were lowered, and in milk Pco(2) was raised and the bicarbonate concentration remained unchanged. Respiratory acidosis and acetazolamide caused a drop in blood pH and in blood and milk bicarbonate concentrations; milk pH remained unchanged, but Pco(2) was raised in both plasma and milk. Acute metabolic alkalosis raised the blood pH and milk Pco(2); plasma Pco(2) and bicarbonate concentrations in blood and milk remained unchanged. The data show that greater changes occur in acid-base parameters of blood than milk when animals are exposed to acidifying and alkalinizing stimuli.", "contents": "Acid-base changes in milk and blood of rats in acidosis and alkalosis. Lactating white rats (Rattus norvegicus) were subjected to metabolic and respiratory acidosis and metabolic alkalosis. Before and during the various treatments, the acid-base status of heart blood and milk was determined. Acute metabolic acidosis lowered the pH of plasma and milk; Pco(2) and bicarbonate concentrations in plasma were lowered, and in milk Pco(2) was raised and the bicarbonate concentration remained unchanged. Respiratory acidosis and acetazolamide caused a drop in blood pH and in blood and milk bicarbonate concentrations; milk pH remained unchanged, but Pco(2) was raised in both plasma and milk. Acute metabolic alkalosis raised the blood pH and milk Pco(2); plasma Pco(2) and bicarbonate concentrations in blood and milk remained unchanged. The data show that greater changes occur in acid-base parameters of blood than milk when animals are exposed to acidifying and alkalinizing stimuli."}
{"id": "PMID:8990", "title": "Role of oxalacetate in lipoate effect on frog gastric mucosa.", "content": "The mechanism of action of lipoate on frog gastric mucosa was investigated. Oxalacetate (OAA) reversed lipoate-inhibited QO2 and QH+ of chambered mucosas by 70 and 40%, respectively. Pyruvate or glucose produced similar effects. Neither activity was affected by OAA when added after glucose, pyruvate, decanoate, butyrate, or lipoate-propionate-inhibited mucosa. Lipoate-treated or lipoate-propionate-treated mucosa did not respond to histamine; OAA addition prior to histamine restored responsiveness. Tracer and chromatographic techniques showed that lipoate reduced and pyruvate increased OAA formation. Preincubation of mitochondrial extracts of gastric mucosa with 2 mM lipoate increased pyruvic dehydrogenase activity 110%. Pyruvic carboxylase (PC) activity was primarily in the mitochondrial fraction of the gastric mucosa. The PC preparation was shown to have an absolute requirement for CoASAc, contained biotin, was not inhibited by lipoate, and had an apparent Km approximately equal to 3.6 X 10(-4) M for pyruvate. The results suggest that OAA concentration is regulated by PC activity and is one of the factors controlling QO2 and QH+ in the frog gastric mucosa.", "contents": "Role of oxalacetate in lipoate effect on frog gastric mucosa. The mechanism of action of lipoate on frog gastric mucosa was investigated. Oxalacetate (OAA) reversed lipoate-inhibited QO2 and QH+ of chambered mucosas by 70 and 40%, respectively. Pyruvate or glucose produced similar effects. Neither activity was affected by OAA when added after glucose, pyruvate, decanoate, butyrate, or lipoate-propionate-inhibited mucosa. Lipoate-treated or lipoate-propionate-treated mucosa did not respond to histamine; OAA addition prior to histamine restored responsiveness. Tracer and chromatographic techniques showed that lipoate reduced and pyruvate increased OAA formation. Preincubation of mitochondrial extracts of gastric mucosa with 2 mM lipoate increased pyruvic dehydrogenase activity 110%. Pyruvic carboxylase (PC) activity was primarily in the mitochondrial fraction of the gastric mucosa. The PC preparation was shown to have an absolute requirement for CoASAc, contained biotin, was not inhibited by lipoate, and had an apparent Km approximately equal to 3.6 X 10(-4) M for pyruvate. The results suggest that OAA concentration is regulated by PC activity and is one of the factors controlling QO2 and QH+ in the frog gastric mucosa."}
{"id": "PMID:8991", "title": "Sensitivity of small subcutaneous vessels to altered respiratory gases and local pH.", "content": "Television microscopy was used to quantitate the responses of small arteries and veins, in the wings of unanesthetized bats, to alterations in the inspired concentrations of O2 and CO2. Mean arterial pressure, heart rate, and the diameters of small arteries (28-54 mum) and veins (50-128 mum) were measured during a 90-min protocol--30 min with an inspiratory gas mixture of 20% O2 and 80% N2 (control period); 30 min with a gas mixture containing 5% O2 (hypoxic period) or 12, 20, or 28% CO2 (hypercapnic period); and 30 min with the original control gas. The hypoxic responses were dilatation of arteries and no change in the veins in both innervated and surgically denervated wings. Hypercapnia resulted in artery dilatation in innervated wings. Hypercapnia resulted in artery dilatation in innervated wings and constriction in denervated wings. The veins constricted in both innervated and denervated wings during the hypercapnia period. In another series, topical application of Krebs solutions (pH ranging from 7.7 to 6.7) to exposed segments of small arteries and veins produced dilatation of both vessels with decreasing pH. Artery dilatation during hypoxia and vein constriction during hypercapnia involve non-neural mechanisms, while both a neural stimulus for dilatation and a non-neural stimulus for constriction are components in the response of innervated arteries to hypercapnia. The non-neural stimulus for artery and vein constriction during hypercapnia is not a local decrease in pH.", "contents": "Sensitivity of small subcutaneous vessels to altered respiratory gases and local pH. Television microscopy was used to quantitate the responses of small arteries and veins, in the wings of unanesthetized bats, to alterations in the inspired concentrations of O2 and CO2. Mean arterial pressure, heart rate, and the diameters of small arteries (28-54 mum) and veins (50-128 mum) were measured during a 90-min protocol--30 min with an inspiratory gas mixture of 20% O2 and 80% N2 (control period); 30 min with a gas mixture containing 5% O2 (hypoxic period) or 12, 20, or 28% CO2 (hypercapnic period); and 30 min with the original control gas. The hypoxic responses were dilatation of arteries and no change in the veins in both innervated and surgically denervated wings. Hypercapnia resulted in artery dilatation in innervated wings. Hypercapnia resulted in artery dilatation in innervated wings and constriction in denervated wings. The veins constricted in both innervated and denervated wings during the hypercapnia period. In another series, topical application of Krebs solutions (pH ranging from 7.7 to 6.7) to exposed segments of small arteries and veins produced dilatation of both vessels with decreasing pH. Artery dilatation during hypoxia and vein constriction during hypercapnia involve non-neural mechanisms, while both a neural stimulus for dilatation and a non-neural stimulus for constriction are components in the response of innervated arteries to hypercapnia. The non-neural stimulus for artery and vein constriction during hypercapnia is not a local decrease in pH."}
{"id": "PMID:8992", "title": "Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs.", "content": "The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (aO2) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood pressure, arterial Pco2, and pH were stabilized before and during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold+platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aO2 and rCBF of these regions were measured polarographically, the latter by the H2-gas clearance technique. Blood flow changed from 42 +/- 2.1 to 28 +/- 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.91 +/- 0.29 to 4.31 +/- 0.52 resistance units (RU) in the thalamus, from  59 +/- 5.0 to 47 +/- 5.0 ml/100 g per min (CVR: from 2.46 +/- 0.28 to 2.92 +/- 0.35 RU) in the hypothalamus, and from 21 +/- 1.0 to 17 +/- 0.8 ml/100 g per min (CVR: from 6.367 +/- 0.35 to 7.672 +/- 0.40 RU) in the white matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue aO2 decreased by 25 +/- 2% in the thalamic and by 19 +/- 2% in the hypothalamic area, relative to the prestimulation level.", "contents": "Hypothalamic and thalamic blood flow during somatic afferent stimulation in dogs. The effect of somatic afferent C fiber stimulation on regional cerebral blood flow (rCBF) and cerebral tissue available oxygen (aO2) was studied in 20 dogs under chloralose anesthesia. Mean arterial blood pressure, arterial Pco2, and pH were stabilized before and during the 3-min stimulation of the sciatic nerves (20 V, 300 ms, 15 Hz). Combined gold+platinum electrodes were chronically implanted into the ventral posterolateral nucleus of the thalamus, ventromedial nucleus of the hypothalamus, and into the white matter. Tissue aO2 and rCBF of these regions were measured polarographically, the latter by the H2-gas clearance technique. Blood flow changed from 42 +/- 2.1 to 28 +/- 1.7 ml/100 g per min (cerebrovascular resistance (CVR), from 2.91 +/- 0.29 to 4.31 +/- 0.52 resistance units (RU) in the thalamus, from  59 +/- 5.0 to 47 +/- 5.0 ml/100 g per min (CVR: from 2.46 +/- 0.28 to 2.92 +/- 0.35 RU) in the hypothalamus, and from 21 +/- 1.0 to 17 +/- 0.8 ml/100 g per min (CVR: from 6.367 +/- 0.35 to 7.672 +/- 0.40 RU) in the white matter during ipsilateral stimulation. Contralateral stimulation of the sciatic nerves caused a more moderate but likewise significant drop in rCBF and an increase in CVR except in the white matter. Parallel to these changes, tissue aO2 decreased by 25 +/- 2% in the thalamic and by 19 +/- 2% in the hypothalamic area, relative to the prestimulation level."}
{"id": "PMID:8993", "title": "Interorgan transport of amino acids in hemorrhagic shock.", "content": "Arterial concentrations and net organ metabolism of amino acids (AA), O2, CO2, H+, and glucose (Glc) were measured in two dogs before and during hemorrhage and after blood replacement. Shock caused increased splanchnic and decreased peripheral blood flow and O2 consumption. Po2 decreased more in hepatic venous than in mixed venous blood. pH fell in hemorrhage and increased with retransfusion. Increased liver output and arterial concentration of Glc were observed during hemorrhage. Differences between animals correlated with nutritional status. Blood concentrations of most AA showed little change during hemorrhage but increased after retransfusion. In contrast, arginine concentrations declined sharply. Peripheral output and hepatic uptake of most AA occurred during the control period. During shock, peripheral output and hepatic uptake of total AA and most individual AA declined progressively; after retransfusion peripheral uptake and hepatic output of many AA occurred. By contrast, peripheral output and hepatic uptake increased for alanine, glutamine, serine, phenylalanine, and tyrosine. After retransfusion net transport of some compounds occurred from periphery to liver; others, from liver to periphery. During shock, hepatic protein catabolism increased. and this catabolism, accompanied by decreased hepatic uptake (increased hepatic output), seemed the main cause of increased blood AA concentrations. Protein catabolism in peripheral tissue was not a cause of increased blood concentrations. Pathological changes in pH, Po2, and blood flow, occurred early in hemorrhage. In contrast, changes in AA movements and concentrations were within normal limits until late in shock.", "contents": "Interorgan transport of amino acids in hemorrhagic shock. Arterial concentrations and net organ metabolism of amino acids (AA), O2, CO2, H+, and glucose (Glc) were measured in two dogs before and during hemorrhage and after blood replacement. Shock caused increased splanchnic and decreased peripheral blood flow and O2 consumption. Po2 decreased more in hepatic venous than in mixed venous blood. pH fell in hemorrhage and increased with retransfusion. Increased liver output and arterial concentration of Glc were observed during hemorrhage. Differences between animals correlated with nutritional status. Blood concentrations of most AA showed little change during hemorrhage but increased after retransfusion. In contrast, arginine concentrations declined sharply. Peripheral output and hepatic uptake of most AA occurred during the control period. During shock, peripheral output and hepatic uptake of total AA and most individual AA declined progressively; after retransfusion peripheral uptake and hepatic output of many AA occurred. By contrast, peripheral output and hepatic uptake increased for alanine, glutamine, serine, phenylalanine, and tyrosine. After retransfusion net transport of some compounds occurred from periphery to liver; others, from liver to periphery. During shock, hepatic protein catabolism increased. and this catabolism, accompanied by decreased hepatic uptake (increased hepatic output), seemed the main cause of increased blood AA concentrations. Protein catabolism in peripheral tissue was not a cause of increased blood concentrations. Pathological changes in pH, Po2, and blood flow, occurred early in hemorrhage. In contrast, changes in AA movements and concentrations were within normal limits until late in shock."}
{"id": "PMID:8994", "title": "Effect of the histamine (H2) inhibitor metiamide on histamine-stimulated bile flow in dogs.", "content": "The effects of the histamine H2-receptor inhibitor metiamide on histamine-stimulated canine bile flow and gastric hydrogen ion output were evaluated. Histamine was found to stimulate bile volume in doses comparable to those that stimulated gastric hydrogen ion output; both responses appeared to have the same maximal response dose, 150 mug/kg per h. Metiamide alone did not alter hepatic bile flow. Administration of metiamide, 2 mg/kg per h, along with various doses of histamine demonstrated that the H2-receptor antagonist decreased bile volume and gastric hydrogen ion output from values obtained with histamine administration alone. The D50 of histamine for bile flow was 16.3 mug/kg per h and the D50 for hydrogen ion output was 44.2 mug/kg per h, Kinetic analysis suggests that the decrease in histamine-stimulated hydrogen ion output produced by metiamide is the result of competitive inhibition; the decrease in histamine-stimulated bile volume by metiamide which is different from the hydrogen ion inhibition, suggests noncompetitive inhibition. These data indicate that the mechanism of histamine choleresis is different from the mechanism of histamine-stimulated gastric acid output and that histamine-stimulated bile flow may not be the result of direct hormone-receptor interaction.", "contents": "Effect of the histamine (H2) inhibitor metiamide on histamine-stimulated bile flow in dogs. The effects of the histamine H2-receptor inhibitor metiamide on histamine-stimulated canine bile flow and gastric hydrogen ion output were evaluated. Histamine was found to stimulate bile volume in doses comparable to those that stimulated gastric hydrogen ion output; both responses appeared to have the same maximal response dose, 150 mug/kg per h. Metiamide alone did not alter hepatic bile flow. Administration of metiamide, 2 mg/kg per h, along with various doses of histamine demonstrated that the H2-receptor antagonist decreased bile volume and gastric hydrogen ion output from values obtained with histamine administration alone. The D50 of histamine for bile flow was 16.3 mug/kg per h and the D50 for hydrogen ion output was 44.2 mug/kg per h, Kinetic analysis suggests that the decrease in histamine-stimulated hydrogen ion output produced by metiamide is the result of competitive inhibition; the decrease in histamine-stimulated bile volume by metiamide which is different from the hydrogen ion inhibition, suggests noncompetitive inhibition. These data indicate that the mechanism of histamine choleresis is different from the mechanism of histamine-stimulated gastric acid output and that histamine-stimulated bile flow may not be the result of direct hormone-receptor interaction."}
{"id": "PMID:8995", "title": "Sympathetic nervous system and renin release from submaxillary glands in vitro.", "content": "We previously reported that alpha- but not beta-adrenergic agonists stimulate renin release from mouse submaxillary glands in vivo. The present studies were undertaken to determine if these in vivo effects were due to a direct action on the submaxillary glands and to find out if cyclic AMP (cAMP) might be involved in submaxillary renin release. Pooled mouse submaxillary gland slices were incubated in Krebs-Ringer bicarbonate medium following a preincubation period, and renin release was measured by a radioimmunoassay for the direct measurement of submaxillary gland renin. Tissue cAMP levels were also measured. Addition of the alpha-adrenergic agonists, phenylephrine or norepinephrine, significantly increased renin release (P less than 0.01 vs. control) while decreasing tissue cAMP levels (P less than 0.01 vs. control). In contrast, addition of the beta-adrenergic agonist isoproterenol markedly increased cAMP levels (P less than 0.01 vs. control) and decreased renin release (P less than 0.05 vs. control). Pretreatment of the slices with the alpha-blocker phenoxy genzamine inhibited the effect of phenylephrine. These results indicate that alpha-adrenergic agonists cause renin release from submaxillary glands which is accompanied by a fall in tissue cAMP levels. This is in contrast to renin release from the kidney which is stimulated by beta-adrenergic agonists.", "contents": "Sympathetic nervous system and renin release from submaxillary glands in vitro. We previously reported that alpha- but not beta-adrenergic agonists stimulate renin release from mouse submaxillary glands in vivo. The present studies were undertaken to determine if these in vivo effects were due to a direct action on the submaxillary glands and to find out if cyclic AMP (cAMP) might be involved in submaxillary renin release. Pooled mouse submaxillary gland slices were incubated in Krebs-Ringer bicarbonate medium following a preincubation period, and renin release was measured by a radioimmunoassay for the direct measurement of submaxillary gland renin. Tissue cAMP levels were also measured. Addition of the alpha-adrenergic agonists, phenylephrine or norepinephrine, significantly increased renin release (P less than 0.01 vs. control) while decreasing tissue cAMP levels (P less than 0.01 vs. control). In contrast, addition of the beta-adrenergic agonist isoproterenol markedly increased cAMP levels (P less than 0.01 vs. control) and decreased renin release (P less than 0.05 vs. control). Pretreatment of the slices with the alpha-blocker phenoxy genzamine inhibited the effect of phenylephrine. These results indicate that alpha-adrenergic agonists cause renin release from submaxillary glands which is accompanied by a fall in tissue cAMP levels. This is in contrast to renin release from the kidney which is stimulated by beta-adrenergic agonists."}
{"id": "PMID:8996", "title": "H+ current response to CO2 and carbonic anhydrase inhibition in turtle bladder.", "content": "To evaluate the role of CO2 and carbonic anhydrase (CA) in H+ transport (JH) by turtle urinary bladder the effect of CO2 addition, with and without addition of CA inhibitiors, was examined on JH. Since in the presence of exogenous CO2 and HCO3- the pH stat-measured rate of mucosal (M) acidification underestimates JH by the rate of electroneutral HCO3- secretion, the reverse short-circuit current (RSCC) applied across ouabain-treated bladders was used to estimate JH. That the RSCC is a measure of JH was demonstrated by: 1) in the absence of added CO2 and HCO3- the rate of M acidification totally accounted for the RSCC, and 2) increases in RSCC with CO2 addition occurred without changes in Na+ and K+ fluxes or the coupled ration of HCO3- secretion for Cl-absorption. When serosal (S) percent CO2 was progressively progressively increased JH achieved a maximum rate of 64 +/- 3 muA (SE) with 4.5% CO2. At higher S percent CO2 JH did not change, suggesting that factors other than the rate of CO2 hydration were rate limiting. The maximum rate of JH was not decreased by low concentrations of CA inhibitors (acetazolamide, 5 X 10(-5) M), although the percent CO2 at which this maximum rate occurred increased to 8.5%. The increased percent CO2 requirement for the maximum rate of JH with low concentrations of CA inhibitors suggests that these agents alter JH by decreasing the rate of enzymatic CO2 hydration. At high concentrations (acetazolamide, 5 X 10(-4) M) these inhibitors decrease the maximum rate of JH in the presence of CO2, implying that these inhibitors at higher concentrations directly interfere with the H+ transport system.", "contents": "H+ current response to CO2 and carbonic anhydrase inhibition in turtle bladder. To evaluate the role of CO2 and carbonic anhydrase (CA) in H+ transport (JH) by turtle urinary bladder the effect of CO2 addition, with and without addition of CA inhibitiors, was examined on JH. Since in the presence of exogenous CO2 and HCO3- the pH stat-measured rate of mucosal (M) acidification underestimates JH by the rate of electroneutral HCO3- secretion, the reverse short-circuit current (RSCC) applied across ouabain-treated bladders was used to estimate JH. That the RSCC is a measure of JH was demonstrated by: 1) in the absence of added CO2 and HCO3- the rate of M acidification totally accounted for the RSCC, and 2) increases in RSCC with CO2 addition occurred without changes in Na+ and K+ fluxes or the coupled ration of HCO3- secretion for Cl-absorption. When serosal (S) percent CO2 was progressively progressively increased JH achieved a maximum rate of 64 +/- 3 muA (SE) with 4.5% CO2. At higher S percent CO2 JH did not change, suggesting that factors other than the rate of CO2 hydration were rate limiting. The maximum rate of JH was not decreased by low concentrations of CA inhibitors (acetazolamide, 5 X 10(-5) M), although the percent CO2 at which this maximum rate occurred increased to 8.5%. The increased percent CO2 requirement for the maximum rate of JH with low concentrations of CA inhibitors suggests that these agents alter JH by decreasing the rate of enzymatic CO2 hydration. At high concentrations (acetazolamide, 5 X 10(-4) M) these inhibitors decrease the maximum rate of JH in the presence of CO2, implying that these inhibitors at higher concentrations directly interfere with the H+ transport system."}
{"id": "PMID:8997", "title": "Effect of potassium depletion on cerebrospinal fluid bicarbonate homeostasis.", "content": "We have examined the effect of K depletion on CSF [HCO3-] homeostasis in awake rats. The relationship of CSF [HCO3-] to arterial [HCO3-] in metabolic acid-base disturbances is displaced is an upward direction and has a significantly increased slope in K-depleted vs. control rats (0.51 +/- 0.02 vs. 0.42 +/- 0.02). Results of partial K-repletion experiments, with peripheral acid-base balance held constant, suggest that the effect is K specific. The K-depleted animals also exhibit a wider (CSF-arterial) PCO2 difference than controls (11.1 vs. 8.4 mmHg). When CSF [HCO3-] is shown as a function of CSF PCO2 the data of K-depleted rats are no longer displaced when compared to controls but still have a significantly greater slope (1.21 +/- 0.23 vs. 0.89 +/- 0.08). This increased slope is interpreted to reflect enhanced HCO3- movement from blood to CSF at high arterial [HCO3-]. Analysis of our data and observations from the literature in conditions of mixed acid-base disturbances suggest that CSF [HCO3-] is determined by a) CSF PCO2 and b) the level of arterial [HCO3-] when the latter is greater than the normal CSF [HCO3-].", "contents": "Effect of potassium depletion on cerebrospinal fluid bicarbonate homeostasis. We have examined the effect of K depletion on CSF [HCO3-] homeostasis in awake rats. The relationship of CSF [HCO3-] to arterial [HCO3-] in metabolic acid-base disturbances is displaced is an upward direction and has a significantly increased slope in K-depleted vs. control rats (0.51 +/- 0.02 vs. 0.42 +/- 0.02). Results of partial K-repletion experiments, with peripheral acid-base balance held constant, suggest that the effect is K specific. The K-depleted animals also exhibit a wider (CSF-arterial) PCO2 difference than controls (11.1 vs. 8.4 mmHg). When CSF [HCO3-] is shown as a function of CSF PCO2 the data of K-depleted rats are no longer displaced when compared to controls but still have a significantly greater slope (1.21 +/- 0.23 vs. 0.89 +/- 0.08). This increased slope is interpreted to reflect enhanced HCO3- movement from blood to CSF at high arterial [HCO3-]. Analysis of our data and observations from the literature in conditions of mixed acid-base disturbances suggest that CSF [HCO3-] is determined by a) CSF PCO2 and b) the level of arterial [HCO3-] when the latter is greater than the normal CSF [HCO3-]."}
{"id": "PMID:8998", "title": "Rational treatment for an irrational disorder: what does the schizophrenic patient need?", "content": "The author discusses the results of a review of controlled studies of treatment approaches to schizophrenia. Although the research evidence strongly supports the efficacy of pharmacotherapy, this finding should not be interpreted as meaning that all schizophrenic patients should receive antipsychotic drugs or that other forms of treatment are unnecessary. The author cautions against doctrinaire attitudes and advocates thoughtful adjustment of goals and methods to meet the needs of the various parties and situations involved in the treatment of the schizophrenic patient.", "contents": "Rational treatment for an irrational disorder: what does the schizophrenic patient need? The author discusses the results of a review of controlled studies of treatment approaches to schizophrenia. Although the research evidence strongly supports the efficacy of pharmacotherapy, this finding should not be interpreted as meaning that all schizophrenic patients should receive antipsychotic drugs or that other forms of treatment are unnecessary. The author cautions against doctrinaire attitudes and advocates thoughtful adjustment of goals and methods to meet the needs of the various parties and situations involved in the treatment of the schizophrenic patient."}
{"id": "PMID:8999", "title": "Infective larvae of Brugia: escape from mosquitoes into water and subsequent oral infectivity in jirds.", "content": "Published work showed that third-stage larvae (L-3s) escape into water from dead or dying, Brugia pahangi-infected, Aedes aegypti. The present study revealed the same escape phenomenon among B. pahangi-infected Armigeres subalbatus, Anopheles quadrimaculatus, and Aedes togoi, and among Brugia malayi-infected Ae. aegypti and Ae. togoi. L-3s maintained in water or in Lum's solution for 3 hours retained infectivity when tested in orally or subcutaneously exposed jirds; furthermore, L-3s recovered from mosquitoes dead for 24 to 48 hours were also infective by either portal of entry in jirds. Since L-3s may escape and remain infective in the field, it is conceivable that natural filarial infections might thus be acquired orally by definitive hosts.", "contents": "Infective larvae of Brugia: escape from mosquitoes into water and subsequent oral infectivity in jirds. Published work showed that third-stage larvae (L-3s) escape into water from dead or dying, Brugia pahangi-infected, Aedes aegypti. The present study revealed the same escape phenomenon among B. pahangi-infected Armigeres subalbatus, Anopheles quadrimaculatus, and Aedes togoi, and among Brugia malayi-infected Ae. aegypti and Ae. togoi. L-3s maintained in water or in Lum's solution for 3 hours retained infectivity when tested in orally or subcutaneously exposed jirds; furthermore, L-3s recovered from mosquitoes dead for 24 to 48 hours were also infective by either portal of entry in jirds. Since L-3s may escape and remain infective in the field, it is conceivable that natural filarial infections might thus be acquired orally by definitive hosts."}
{"id": "PMID:9000", "title": "Experimental studies on the transmission of hepatitis B by mosquitoes.", "content": "Culex tarsalis and Aedes aegypti mosquitoes were fed on chimpanzees carrying hepatitis B surface antigen (HBS Ag) of known infectivity and pools were tested by radioimmunoassay daily for the presence of HBS Ag. HBS Ag continued to be detected at low levels in mosquito tissue after digestion of the blood meal. Inoculation of susceptible chimpanzees with macerated pools of A. aegypti mosquitoes at two intervals after digestion of the blood meal did not produce hepatitis or serologic evidence of hepatitis B virus infection. Mechanical transmission studies by interrupting feeding of A aegypti from HBS Ag-carrier chimpanzees and transferring them to susceptible chimpanzees did not produce hepatitis. These findings do not support the hypothesis that mosquitoes are involved in either biological or mechanical transmission of hepatitis B.", "contents": "Experimental studies on the transmission of hepatitis B by mosquitoes. Culex tarsalis and Aedes aegypti mosquitoes were fed on chimpanzees carrying hepatitis B surface antigen (HBS Ag) of known infectivity and pools were tested by radioimmunoassay daily for the presence of HBS Ag. HBS Ag continued to be detected at low levels in mosquito tissue after digestion of the blood meal. Inoculation of susceptible chimpanzees with macerated pools of A. aegypti mosquitoes at two intervals after digestion of the blood meal did not produce hepatitis or serologic evidence of hepatitis B virus infection. Mechanical transmission studies by interrupting feeding of A aegypti from HBS Ag-carrier chimpanzees and transferring them to susceptible chimpanzees did not produce hepatitis. These findings do not support the hypothesis that mosquitoes are involved in either biological or mechanical transmission of hepatitis B."}
{"id": "PMID:9001", "title": "Plasma activities of lysosomal enzymes after hepatic dearterialization in man.", "content": "Six patients with liver metastases from carcinoid or colon carcinoma underwent hepatic derterialization. This operation, known to cause both tumor necrosis and liver cell damage, caused considerable increases of several lysosomal acid hydrolases in the circulation. Thus, beta-glucosidase showed a small temporary increase during the operation, followed by a slower but higher reaction reaching a maximum 12 to 36 hours postoperatively. Similar reactions were noted for beta-glucuronidase, acid phosphatase, beta-galactosidase, arylsuphatase A, and N-acetyl-beta-glucosaminidase while no reactions were found for cathepsin D. Very high enzyme levels occurred in a patient dying from bleeding complications in the postoperative period.", "contents": "Plasma activities of lysosomal enzymes after hepatic dearterialization in man. Six patients with liver metastases from carcinoid or colon carcinoma underwent hepatic derterialization. This operation, known to cause both tumor necrosis and liver cell damage, caused considerable increases of several lysosomal acid hydrolases in the circulation. Thus, beta-glucosidase showed a small temporary increase during the operation, followed by a slower but higher reaction reaching a maximum 12 to 36 hours postoperatively. Similar reactions were noted for beta-glucuronidase, acid phosphatase, beta-galactosidase, arylsuphatase A, and N-acetyl-beta-glucosaminidase while no reactions were found for cathepsin D. Very high enzyme levels occurred in a patient dying from bleeding complications in the postoperative period."}
{"id": "PMID:9005", "title": "[Combined acupuncture analgesia and controlled respiration. A new modified method of anesthesia in open heart surgery (author's transl)].", "content": "From October 1973 to May 1975 cardiae surgery with extracorporal circulation using Acupuncture as Analgesia was performed in 131 patients in the surgical clinic of the University of Giessen. Acupuncture is performed by electric-stimulation of 8 points at the lower legs, the neck and ears with 90 V and 5--6 Htz. All patients are intubated; controlled respiration is maintained with 50% O2 and 50% N2o. During the whole operation, 20 min after intubation the patients are responsible. The main advantage of the new method we see in a good postoperative cooperation of the patients, which are generally extubated in the operation-room.", "contents": "[Combined acupuncture analgesia and controlled respiration. A new modified method of anesthesia in open heart surgery (author's transl)]. From October 1973 to May 1975 cardiae surgery with extracorporal circulation using Acupuncture as Analgesia was performed in 131 patients in the surgical clinic of the University of Giessen. Acupuncture is performed by electric-stimulation of 8 points at the lower legs, the neck and ears with 90 V and 5--6 Htz. All patients are intubated; controlled respiration is maintained with 50% O2 and 50% N2o. During the whole operation, 20 min after intubation the patients are responsible. The main advantage of the new method we see in a good postoperative cooperation of the patients, which are generally extubated in the operation-room."}
{"id": "PMID:9019", "title": "On the morphology of the human Sertoli cells under normal conditions and in patients with impaired fertility.", "content": "Sertoli cells in testicular biopsies from 7 patients with Sertoli-cell only syndrome, 8 patients who had been treated with cyclophosphamide for testicular neoplasia, 8 patients with oligozoospermia, 7 patients with cryptorchidism, and 8 patients with seminoma were examined under the electron microscope and compared with Sertoli cells of normal tissues. The investigations reveal that each of these conditions of impaired fertility is characterized of a special type of Sertoli cell. The cell pattern is either restricted to one or two of the normally occurring cell types, or modified cells predominate that might be typical of the underlying disturbances of spermatogenesis. It is suggested that the cell type which prevails in the Sertoli-cell only syndrome is capable of maintaining a basic production of a substance that inhibits FSH secretion.", "contents": "On the morphology of the human Sertoli cells under normal conditions and in patients with impaired fertility. Sertoli cells in testicular biopsies from 7 patients with Sertoli-cell only syndrome, 8 patients who had been treated with cyclophosphamide for testicular neoplasia, 8 patients with oligozoospermia, 7 patients with cryptorchidism, and 8 patients with seminoma were examined under the electron microscope and compared with Sertoli cells of normal tissues. The investigations reveal that each of these conditions of impaired fertility is characterized of a special type of Sertoli cell. The cell pattern is either restricted to one or two of the normally occurring cell types, or modified cells predominate that might be typical of the underlying disturbances of spermatogenesis. It is suggested that the cell type which prevails in the Sertoli-cell only syndrome is capable of maintaining a basic production of a substance that inhibits FSH secretion."}
{"id": "PMID:9020", "title": "Interaction of anesthesia, beta-receptor blockade, and blood loss in dogs with induced myocardial infarction.", "content": "The cardiovascular effects of halothane-nitrous oxide anesthesia, and beta-receptor blockade with either propranolol or practolol, were studied in 15 dogs in which severe myocardial infarction had been induced ten days earlier. The hemodynamic responses to blood loss amounting to 25 per cent of estimated blood volume, and its subsequent replacement, were studied before and after induction of beta-receptor blockade. In terms of cardiac output and aortic blood flow acceleration, cardiac performance in the absence of beta-blockade was markedly impaired during steady-state anesthesia, compared with corresponding values in normal dogs. Practolol (2.0 mg/kg) administered during anesthesia induced no significant circulatory change other than a 14 per cent decrease in heart rate and a 25 per cent increase in strode volum. Propranolol (0.3 mg/kg) caused a comparable reduction of heart rate, but significantly reduced cardiac output (-27 per cent), aortic blood flow acceleration (-26 per cent), and peak LV power (-19 per cent), and increased systemic vascular resistance (+49 per cent). The two drugs caused comparable shifts of the isoproterenol dose-response curve during anesthesia. Graduated blood loss during anesthesia, to a total of 25 per cent of blood volume, caused consistent circulatory changes (decreased mean arterial pressure cardiac output, peak LV power, LV minute work) that were essentially similar before and after beta-receptor blockade with either propranolol or practolol. The positive inotropic effect of calcium gluconate during halothane anesthesia was significantly reduced following either propranolol or practolol, but the hemodynamic responses to changes of systemic vascular resistance induced with acetylcholine or phenylephrine were not modified by beta-receptor blockade.", "contents": "Interaction of anesthesia, beta-receptor blockade, and blood loss in dogs with induced myocardial infarction. The cardiovascular effects of halothane-nitrous oxide anesthesia, and beta-receptor blockade with either propranolol or practolol, were studied in 15 dogs in which severe myocardial infarction had been induced ten days earlier. The hemodynamic responses to blood loss amounting to 25 per cent of estimated blood volume, and its subsequent replacement, were studied before and after induction of beta-receptor blockade. In terms of cardiac output and aortic blood flow acceleration, cardiac performance in the absence of beta-blockade was markedly impaired during steady-state anesthesia, compared with corresponding values in normal dogs. Practolol (2.0 mg/kg) administered during anesthesia induced no significant circulatory change other than a 14 per cent decrease in heart rate and a 25 per cent increase in strode volum. Propranolol (0.3 mg/kg) caused a comparable reduction of heart rate, but significantly reduced cardiac output (-27 per cent), aortic blood flow acceleration (-26 per cent), and peak LV power (-19 per cent), and increased systemic vascular resistance (+49 per cent). The two drugs caused comparable shifts of the isoproterenol dose-response curve during anesthesia. Graduated blood loss during anesthesia, to a total of 25 per cent of blood volume, caused consistent circulatory changes (decreased mean arterial pressure cardiac output, peak LV power, LV minute work) that were essentially similar before and after beta-receptor blockade with either propranolol or practolol. The positive inotropic effect of calcium gluconate during halothane anesthesia was significantly reduced following either propranolol or practolol, but the hemodynamic responses to changes of systemic vascular resistance induced with acetylcholine or phenylephrine were not modified by beta-receptor blockade."}
{"id": "PMID:9025", "title": "Characterization and tissue distribution of N-acetyl hexosaminidase C: suggestive evidence for a separate hexosaminidase locus.", "content": "1. An electrophoretic system in which N-acetyl hexosaminidase C (HEX(C)) MIGRATES LESS ANODALLY THAN N-acetyl hexosaminidase A (HEX(A)) is described. 2. HEX(C) is shown to differ from HEX(A) and HEX(B) in substrate specificity, molecular size and affinity for Concanavalin-A. 3. HEX(C) is present in a wide range of adult and foetal tissues and in tissues from patients with Tay-Sachs and Sandhoff's diseases. It is particularly prominent in brain, testis, thymus and lymphoblastoid cell extracts and in several foetal tissues. 4. It is suggested that HEX(C) is coded at a separate gene locus from HEX(A) and HEX(B).", "contents": "Characterization and tissue distribution of N-acetyl hexosaminidase C: suggestive evidence for a separate hexosaminidase locus. 1. An electrophoretic system in which N-acetyl hexosaminidase C (HEX(C)) MIGRATES LESS ANODALLY THAN N-acetyl hexosaminidase A (HEX(A)) is described. 2. HEX(C) is shown to differ from HEX(A) and HEX(B) in substrate specificity, molecular size and affinity for Concanavalin-A. 3. HEX(C) is present in a wide range of adult and foetal tissues and in tissues from patients with Tay-Sachs and Sandhoff's diseases. It is particularly prominent in brain, testis, thymus and lymphoblastoid cell extracts and in several foetal tissues. 4. It is suggested that HEX(C) is coded at a separate gene locus from HEX(A) and HEX(B)."}
{"id": "PMID:9024", "title": "Monitoring the administration of methotrexate in antimetabolite therapy.", "content": "An enzymatic method for the measurement of methotrexate (MTX) in serum is presented in which the inhibition of the enzyme dihydrofolate reductase by MTX is measured. Reduction of the substrate dihydrofolate by the enzyme and cofactor NADPH is lessened in direct proportion to the amount of MTX present. Measurements can be made in the \"therapeutic range\" of MTX which corresponds to the 10(-7) to 10(-8) M concentration of MTX in serum.", "contents": "Monitoring the administration of methotrexate in antimetabolite therapy. An enzymatic method for the measurement of methotrexate (MTX) in serum is presented in which the inhibition of the enzyme dihydrofolate reductase by MTX is measured. Reduction of the substrate dihydrofolate by the enzyme and cofactor NADPH is lessened in direct proportion to the amount of MTX present. Measurements can be made in the \"therapeutic range\" of MTX which corresponds to the 10(-7) to 10(-8) M concentration of MTX in serum."}
{"id": "PMID:9029", "title": "Stool and urinary sugars in normal neonates.", "content": "The pH of the stool and the amount of reducing substances present were observed in 51 normal neonates aged 5 to 8 days. A stool pH of 5 or less was found in 6, 4 of whom were exclusively breast fed. Reducing substances, 0-5% or more, were found in the stools of 16. Stool chromatography in 13 showed lactose, glucose, galactose, or a variable combination of these sugars--that is, a pattern consistent with lactose malabsorption. The stools of 3 infants contained oligosaccharides or maltose only. Chromatography of urine from 60 normal neonates showed detectable sugars in 11 but only 3 had levels above 50 mg/100 ml.", "contents": "Stool and urinary sugars in normal neonates. The pH of the stool and the amount of reducing substances present were observed in 51 normal neonates aged 5 to 8 days. A stool pH of 5 or less was found in 6, 4 of whom were exclusively breast fed. Reducing substances, 0-5% or more, were found in the stools of 16. Stool chromatography in 13 showed lactose, glucose, galactose, or a variable combination of these sugars--that is, a pattern consistent with lactose malabsorption. The stools of 3 infants contained oligosaccharides or maltose only. Chromatography of urine from 60 normal neonates showed detectable sugars in 11 but only 3 had levels above 50 mg/100 ml."}
{"id": "PMID:9030", "title": "HCG stimulation test in children with abnormal sexual development.", "content": "Plasma testosterone was estimated by radioimmunoassay in 60 children with disorders of sexual development before and after stimulation with human chorionic gonadotrophin (HCG). In 21 children the testosterone levels after 3 and 5 daily injections of 1000 units HCG were compared and good correlation was found between the paired results (r =0-93), suggesting that the 5-day HCG test has no advantage over the 3-day test. In 7 boys with apparently normal genital development the increments in plasma testosterone ranged from 2-0 to 8-5 nmol/1 after 3 injections of HCG. 10 boys with anorchia showed little response to HCG stimulation, but in patients with other disorders, such as micropenis (10), cryptorchidism (8), hermaphroditism (3), male pseudohermaphroditism (13), hypospadias (3), and sex chromosome anomalies (6), there was considerable variation in the plasma testosterone level after HCG. In 2 boys with suspected anorchia the results suggested that testes were present and this was confirmed at operation.", "contents": "HCG stimulation test in children with abnormal sexual development. Plasma testosterone was estimated by radioimmunoassay in 60 children with disorders of sexual development before and after stimulation with human chorionic gonadotrophin (HCG). In 21 children the testosterone levels after 3 and 5 daily injections of 1000 units HCG were compared and good correlation was found between the paired results (r =0-93), suggesting that the 5-day HCG test has no advantage over the 3-day test. In 7 boys with apparently normal genital development the increments in plasma testosterone ranged from 2-0 to 8-5 nmol/1 after 3 injections of HCG. 10 boys with anorchia showed little response to HCG stimulation, but in patients with other disorders, such as micropenis (10), cryptorchidism (8), hermaphroditism (3), male pseudohermaphroditism (13), hypospadias (3), and sex chromosome anomalies (6), there was considerable variation in the plasma testosterone level after HCG. In 2 boys with suspected anorchia the results suggested that testes were present and this was confirmed at operation."}
{"id": "PMID:9031", "title": "Human skin proteases. Fractionation of psoriasis scale proteases and separation of a plasminogen activator and a histone hydrolysing protease.", "content": "Psoriatic scale proteases were found to be extracted effectively in salt solution (1 mol/l) containing Triton X-100 (5 g/l). The extraction in dilute buffer or sucrose yielded low activities. The acid (0.25 N H2SO4) and KSCN (2 mol/l) solutions effectively extracted plasminogen activator. Fibrinolysin was most active in salt (1 mol/l KCl) and in KSCN (2 mol/l) extracts. Psoriatic scale proteases were fractionated by Sephadex G-100 gel filtration and further by DEAE cellulose chromatography. Five different enzyme preparations were obtained. The first preparation, resembling cathepsin D, effectively hydrolysed hemoglobin at pH 3.5 and casein at pH 5.8 and was insensitive to protease modifiers. The second preparation effectively hydrolysed trypsin substrates (AGLME, TAME, BAEE and BANA) and also histone and casein at pH 7.2 and was inhibited by protease inhibitors, TLCK and E-600. The third preparation hydrolysed histone and casein at pH 10.2 and was effectively inhibited by E-600 and partially by protease inhibitors and TPCK. The fourth preparation, resembling cathepsin B1, hydrolysed BANA and BAEE at pH 5.8 and was activated by SH-reagents and EDTA. The fifth enzyme preparation hydrolysed ATEE and was inhibited by E-600 and TPCK. Plasminogen activator was found mainly in the second enzyme preparation and fibrinolysin activity in the third and fifth enzyme preparations. The second, third and fifth enzyme preparations were different from the enzymes found in healthy human skin. The proteases of psoriatic scale resemble those of tissue and cell cultures undergoing rapid cell division. The possible role of proteases in the increased cell division in psoriasis plaque is discussed.", "contents": "Human skin proteases. Fractionation of psoriasis scale proteases and separation of a plasminogen activator and a histone hydrolysing protease. Psoriatic scale proteases were found to be extracted effectively in salt solution (1 mol/l) containing Triton X-100 (5 g/l). The extraction in dilute buffer or sucrose yielded low activities. The acid (0.25 N H2SO4) and KSCN (2 mol/l) solutions effectively extracted plasminogen activator. Fibrinolysin was most active in salt (1 mol/l KCl) and in KSCN (2 mol/l) extracts. Psoriatic scale proteases were fractionated by Sephadex G-100 gel filtration and further by DEAE cellulose chromatography. Five different enzyme preparations were obtained. The first preparation, resembling cathepsin D, effectively hydrolysed hemoglobin at pH 3.5 and casein at pH 5.8 and was insensitive to protease modifiers. The second preparation effectively hydrolysed trypsin substrates (AGLME, TAME, BAEE and BANA) and also histone and casein at pH 7.2 and was inhibited by protease inhibitors, TLCK and E-600. The third preparation hydrolysed histone and casein at pH 10.2 and was effectively inhibited by E-600 and partially by protease inhibitors and TPCK. The fourth preparation, resembling cathepsin B1, hydrolysed BANA and BAEE at pH 5.8 and was activated by SH-reagents and EDTA. The fifth enzyme preparation hydrolysed ATEE and was inhibited by E-600 and TPCK. Plasminogen activator was found mainly in the second enzyme preparation and fibrinolysin activity in the third and fifth enzyme preparations. The second, third and fifth enzyme preparations were different from the enzymes found in healthy human skin. The proteases of psoriatic scale resemble those of tissue and cell cultures undergoing rapid cell division. The possible role of proteases in the increased cell division in psoriasis plaque is discussed."}
{"id": "PMID:9032", "title": "Sympathomimetic-induced effects in the soleus muscle of the guinea-pig.", "content": "Sympathomimetic amines reduced the peak tension, time to peak and time to half-relaxation of indirectly elicited twitches of the guinea-pig soleus muscle in vivo. Clonic contractions of the soleus muscle were depressed by the amines. On a molar basis salbutamol and orciprenaline were 5.12 and 80.0 times less potent than (+/-)-isoprenaline in producing these effects. Results obtained with the beta-receptor antagonists propranolol, practolol and H35/25 suggest that the depression in skeletal muscle contractility is due to beta2-adrenoreceptor stimulation. The effects of the amines on twitches and clonic contractions of the guinea-pig soleus muscle are qualitatively similar to those reported previously in the cat soleus muscle preparation, which has been used to assess the possible tremorogenic actions of sympathomimetic bronchodilators. On a quantitative basis the molar dose-ratios of the sympathomimetics used, and the effects of beta-receptor antagonists on the responses, are similar in the two species.", "contents": "Sympathomimetic-induced effects in the soleus muscle of the guinea-pig. Sympathomimetic amines reduced the peak tension, time to peak and time to half-relaxation of indirectly elicited twitches of the guinea-pig soleus muscle in vivo. Clonic contractions of the soleus muscle were depressed by the amines. On a molar basis salbutamol and orciprenaline were 5.12 and 80.0 times less potent than (+/-)-isoprenaline in producing these effects. Results obtained with the beta-receptor antagonists propranolol, practolol and H35/25 suggest that the depression in skeletal muscle contractility is due to beta2-adrenoreceptor stimulation. The effects of the amines on twitches and clonic contractions of the guinea-pig soleus muscle are qualitatively similar to those reported previously in the cat soleus muscle preparation, which has been used to assess the possible tremorogenic actions of sympathomimetic bronchodilators. On a quantitative basis the molar dose-ratios of the sympathomimetics used, and the effects of beta-receptor antagonists on the responses, are similar in the two species."}
{"id": "PMID:9033", "title": "The effects of the beta-adrenoceptor blocking agent LL 21-945 on renal hypertensive (Grollman) rats.", "content": "Prophylactic administration of LL 21-945 [4-(3-tert. butyl-amino-2-pivaloyloxypropoxy)-9-fluorenone] during 15 weeks to Grollman rats depressed the development of hypertension, tachycardia and myocardial pathogical changes. The tachycardia was eliminated and the degree of the myocardial pathological changes and coronary sclerosis was less severe than in the untreated Grollman rats. The survival rate was slightly improved with LL 21-945. With respect to the biochemical parameters studied, only a tendency of LL 21-945 to moderate the rises in blood cholesterol, total glycerides and urea was observed towards the end of the experiment.", "contents": "The effects of the beta-adrenoceptor blocking agent LL 21-945 on renal hypertensive (Grollman) rats. Prophylactic administration of LL 21-945 [4-(3-tert. butyl-amino-2-pivaloyloxypropoxy)-9-fluorenone] during 15 weeks to Grollman rats depressed the development of hypertension, tachycardia and myocardial pathogical changes. The tachycardia was eliminated and the degree of the myocardial pathological changes and coronary sclerosis was less severe than in the untreated Grollman rats. The survival rate was slightly improved with LL 21-945. With respect to the biochemical parameters studied, only a tendency of LL 21-945 to moderate the rises in blood cholesterol, total glycerides and urea was observed towards the end of the experiment."}
{"id": "PMID:9034", "title": "Mesenteric vasodilator effect of 5-hydroxytryptamine: possible enteric neuron mediation.", "content": "The superior mesenteric blood flow response to intra-arterial injections (0.5-25 mug) and infusions (5-30 mug/min) of 5-hydroxytryptamine (5-HT, serotonin) was investigated in anesthetized cats in which nerve activity to the intestine was altered by surgical and pharmacological procedures. With the superior mesenteric periarterial nerves intact, low doses of 5-HT (less than 5 mug) produce vasodilatation, whereas higher doses produce vasoconstriction. When the periarterial nerves are cut either at the start of or during the experiments, vasodilatation is elicited over the entire dose range, and doses of 5-HT which initially produce vasoconstriction elicit vasodilatation after nerve sectioning and also after alpha-adrenergic receptor blockade. These vascular responses are not secondary to changes in arterial pressure or intestinal motility. The vasodilator response to 5-HT is unaffected by alpha- or beta-adrenergic or cholinergic receptor blockade, by ganglionic blockade, or by histamine receptor blockade, but is blocked by tetrodotoxin and also the 5-HT antagonist, dihydroergotamine.", "contents": "Mesenteric vasodilator effect of 5-hydroxytryptamine: possible enteric neuron mediation. The superior mesenteric blood flow response to intra-arterial injections (0.5-25 mug) and infusions (5-30 mug/min) of 5-hydroxytryptamine (5-HT, serotonin) was investigated in anesthetized cats in which nerve activity to the intestine was altered by surgical and pharmacological procedures. With the superior mesenteric periarterial nerves intact, low doses of 5-HT (less than 5 mug) produce vasodilatation, whereas higher doses produce vasoconstriction. When the periarterial nerves are cut either at the start of or during the experiments, vasodilatation is elicited over the entire dose range, and doses of 5-HT which initially produce vasoconstriction elicit vasodilatation after nerve sectioning and also after alpha-adrenergic receptor blockade. These vascular responses are not secondary to changes in arterial pressure or intestinal motility. The vasodilator response to 5-HT is unaffected by alpha- or beta-adrenergic or cholinergic receptor blockade, by ganglionic blockade, or by histamine receptor blockade, but is blocked by tetrodotoxin and also the 5-HT antagonist, dihydroergotamine."}
{"id": "PMID:9035", "title": "Electrophysiologically determined quinidine-like actions of a beta-adrenergic blocking agent, 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2).", "content": "Since 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2) has been reported to be a potent beta-adrenergic blocking agent with antiarrhythmic effects, the electrophysiological effects of this compound on guinea-pig and canine heart muscle were examined. YB-2 was found to have typical quinidine-like actions such as decrease in rate of rise of the action potential, prolongation of refractory period and decrease in conduction velocity.", "contents": "Electrophysiologically determined quinidine-like actions of a beta-adrenergic blocking agent, 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2). Since 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2) has been reported to be a potent beta-adrenergic blocking agent with antiarrhythmic effects, the electrophysiological effects of this compound on guinea-pig and canine heart muscle were examined. YB-2 was found to have typical quinidine-like actions such as decrease in rate of rise of the action potential, prolongation of refractory period and decrease in conduction velocity."}
{"id": "PMID:9036", "title": "The effect of trimepranol on the binding of [3H] norepinephrine in myocardial subcellular fractions of the dog.", "content": "The effect of Trimepranol on the binding of 3H norepinephrine to myocardial particles from dogs (to fractions 1,000 g and 78,000 g resp.) has been studied and compared with the effect of propranolol, isoprenaline, phentolamine and ephedrine. Displacement of 3H norepinephrine by propranolol and isoprenaline was found in both fractions. Trimepranol, in low concentrations, inhibited the binding of 3H norepinephrine; in higher concentrations the binding of 3H norepinephrine was stimulated. Phentolamine and ephedrine were without effect in both fractions. The problem of specificity of adrenergic binding sites is discussed.", "contents": "The effect of trimepranol on the binding of [3H] norepinephrine in myocardial subcellular fractions of the dog. The effect of Trimepranol on the binding of 3H norepinephrine to myocardial particles from dogs (to fractions 1,000 g and 78,000 g resp.) has been studied and compared with the effect of propranolol, isoprenaline, phentolamine and ephedrine. Displacement of 3H norepinephrine by propranolol and isoprenaline was found in both fractions. Trimepranol, in low concentrations, inhibited the binding of 3H norepinephrine; in higher concentrations the binding of 3H norepinephrine was stimulated. Phentolamine and ephedrine were without effect in both fractions. The problem of specificity of adrenergic binding sites is discussed."}
{"id": "PMID:9037", "title": "Regional variation in the distribution of alpha-adrenoreceptors in the vas deferens of the rat.", "content": "Experiments were performed with preparations obtained by medial transection of the rat vas deferens. Eight sympathomimetic drugs: noradrenaline, alpha-methylnoradrenaline, phenylephrine, dopamine, tyramine, amphetamine, cocaine and isoprenaline, were applied to preparations which were field-stimulated at 10 sec intervals. On the testicular half of the tissue all except isoprenaline enhanced twitches and/or caused contractions. These effects were blocked by alpha-adrenoreceptor antagonists. On the urethral preparation all except phenylephrine, which often enhanced twitches, inhibited responses to field stimulation. These effects were not blocked by alpha-adrenoreceptor antagonists or by propranolol, though the latter blocked inhibitory effects of isoprenaline on both segments. Inhibitory responses to tyramine persisted in urethral segments treated with cocaine and in urethral segments taken from reserpine-treated rats, and thus tyramine may have some direct action. No regional variation was observed in response to acetylcholine or carbachol. High potassium concentrations were equally effective in contracting both segments, but the time courses of contractions differed. These experiments confirm a density gradient of excitatory alpha-adrenoreceptors along the length of the rat vas deferens.", "contents": "Regional variation in the distribution of alpha-adrenoreceptors in the vas deferens of the rat. Experiments were performed with preparations obtained by medial transection of the rat vas deferens. Eight sympathomimetic drugs: noradrenaline, alpha-methylnoradrenaline, phenylephrine, dopamine, tyramine, amphetamine, cocaine and isoprenaline, were applied to preparations which were field-stimulated at 10 sec intervals. On the testicular half of the tissue all except isoprenaline enhanced twitches and/or caused contractions. These effects were blocked by alpha-adrenoreceptor antagonists. On the urethral preparation all except phenylephrine, which often enhanced twitches, inhibited responses to field stimulation. These effects were not blocked by alpha-adrenoreceptor antagonists or by propranolol, though the latter blocked inhibitory effects of isoprenaline on both segments. Inhibitory responses to tyramine persisted in urethral segments treated with cocaine and in urethral segments taken from reserpine-treated rats, and thus tyramine may have some direct action. No regional variation was observed in response to acetylcholine or carbachol. High potassium concentrations were equally effective in contracting both segments, but the time courses of contractions differed. These experiments confirm a density gradient of excitatory alpha-adrenoreceptors along the length of the rat vas deferens."}
{"id": "PMID:9038", "title": "Studies on the action and interaction of dopamine and prostaglandin A1 in the renal vasculature.", "content": "Dopamine (3 mug/kg/min) and prostaglandin A1 (0.2 mug/kg/min) were found to dilate the renal vasculature and increase total kidney blood flow in be anesthetized dog. These effects of dopamine, but not of prostaglandin A1, were completely antagonized by bulbocapnine, a selective dopamine receptor inhibitor, at a dose (3 mg/kg) which did not itself significantly alter cardiovascular hemodynamics. Conversely, indomethacin, an inhibitor of prostaglandin synthetase in the dog at 2 mg/kg, did not reduce the dopamin renal vascular response. These results suggest that dopamine and PGA1 decrease renal vascular resistance in the dog via distinct pharmacological mechanisms.", "contents": "Studies on the action and interaction of dopamine and prostaglandin A1 in the renal vasculature. Dopamine (3 mug/kg/min) and prostaglandin A1 (0.2 mug/kg/min) were found to dilate the renal vasculature and increase total kidney blood flow in be anesthetized dog. These effects of dopamine, but not of prostaglandin A1, were completely antagonized by bulbocapnine, a selective dopamine receptor inhibitor, at a dose (3 mg/kg) which did not itself significantly alter cardiovascular hemodynamics. Conversely, indomethacin, an inhibitor of prostaglandin synthetase in the dog at 2 mg/kg, did not reduce the dopamin renal vascular response. These results suggest that dopamine and PGA1 decrease renal vascular resistance in the dog via distinct pharmacological mechanisms."}
{"id": "PMID:9040", "title": "Morphological features of red blood cells in subjects with sickle cell trait: changes during exercise.", "content": "Occasional complications and even death in subjects with sickle cell trait have been attributed to severe physical exertion. However, the extent to which sickling actually occurs during exercise has not been reported. This study examined the red blood cell morphological features immediately following near maximal upright graded bicycle exercise in five asymptomatic black subjects with hemoglobin AS. Exercise produced minimal sickling in vivo, which was not proportional to the intensity of exercise. The amount of sickling in vivo was small in comparison to that observed in the presence of severe hypoxia in vitro, never exceeding 0.75%. in seven normal subjects with hemoglobin AA, exercise did not cause changes in red blood cell morphological features. We conclude that exercise may initiate sickling in subjects with sickle cell trait.", "contents": "Morphological features of red blood cells in subjects with sickle cell trait: changes during exercise. Occasional complications and even death in subjects with sickle cell trait have been attributed to severe physical exertion. However, the extent to which sickling actually occurs during exercise has not been reported. This study examined the red blood cell morphological features immediately following near maximal upright graded bicycle exercise in five asymptomatic black subjects with hemoglobin AS. Exercise produced minimal sickling in vivo, which was not proportional to the intensity of exercise. The amount of sickling in vivo was small in comparison to that observed in the presence of severe hypoxia in vitro, never exceeding 0.75%. in seven normal subjects with hemoglobin AA, exercise did not cause changes in red blood cell morphological features. We conclude that exercise may initiate sickling in subjects with sickle cell trait."}
{"id": "PMID:9041", "title": "Lactic acidosis in diabetic patients.", "content": "Plasma lactate and beta-hydroxybutyrate concentrations were measured during episodes of ketoacidosis and lactic acidosis in diabetics. In 39 patients with ketoacidosis, with a mean plasma beta-hydroxybutyrate concentration of 12.4 millimols/liter, the plasma lactate concentration was less than 3.6 millimols/liter in 28 and moderately elevated in 11. In seven of the latter, coexisting lactic acidosis had been suspected clinically. In these 39 patients, there was no correlation between plasma lactate and beta-hydroxybutyrate concentrations. In six of ten episodes of presumed and later proved lactic acidosis, despite negative or weakly positive serum reactions with sodium nitroprusside, the plasma beta-hydroxybutyrate concentration was elevated. Although positive, the serum reaction with nitroprusside was also misleadingly weak in five of 39 patients with ketoacidosis, including three with plasma lactate concentrations less than 3 millimols/liter.", "contents": "Lactic acidosis in diabetic patients. Plasma lactate and beta-hydroxybutyrate concentrations were measured during episodes of ketoacidosis and lactic acidosis in diabetics. In 39 patients with ketoacidosis, with a mean plasma beta-hydroxybutyrate concentration of 12.4 millimols/liter, the plasma lactate concentration was less than 3.6 millimols/liter in 28 and moderately elevated in 11. In seven of the latter, coexisting lactic acidosis had been suspected clinically. In these 39 patients, there was no correlation between plasma lactate and beta-hydroxybutyrate concentrations. In six of ten episodes of presumed and later proved lactic acidosis, despite negative or weakly positive serum reactions with sodium nitroprusside, the plasma beta-hydroxybutyrate concentration was elevated. Although positive, the serum reaction with nitroprusside was also misleadingly weak in five of 39 patients with ketoacidosis, including three with plasma lactate concentrations less than 3 millimols/liter."}
{"id": "PMID:9043", "title": "Effect of the pH of culture medium on the alkalophilicity of a species of Bacillus.", "content": "The amino acid incorporation and alpha-amino-isobutyric acid (AIB) uptake of an alkalophilic Bacillus grown at pH 8.2 (the pH 8-bacteria) were much less pH dependent (less alkalophilic) than those of the organisms grown at pH 10.0 (the pH 10-bacteria), respectively. The rate of AIB uptake of the pH 10-bacteria was almost the same as that of the pH 8-bacteria, while the rate of amino acid incorporation of the pH 10-bacteria was higher than that of the pH 8-bacteria in alkaline environments. The colloidal titration with clupein showed that the amount of negative charge on the pH 10-bacteria was greater than that of the pH 8-bacteria in alkaline environments. Considerable difference in protein composition was observed between the membranes of the pH 8- and 10-bacteria while no difference was observed in phospholipid composition.", "contents": "Effect of the pH of culture medium on the alkalophilicity of a species of Bacillus. The amino acid incorporation and alpha-amino-isobutyric acid (AIB) uptake of an alkalophilic Bacillus grown at pH 8.2 (the pH 8-bacteria) were much less pH dependent (less alkalophilic) than those of the organisms grown at pH 10.0 (the pH 10-bacteria), respectively. The rate of AIB uptake of the pH 10-bacteria was almost the same as that of the pH 8-bacteria, while the rate of amino acid incorporation of the pH 10-bacteria was higher than that of the pH 8-bacteria in alkaline environments. The colloidal titration with clupein showed that the amount of negative charge on the pH 10-bacteria was greater than that of the pH 8-bacteria in alkaline environments. Considerable difference in protein composition was observed between the membranes of the pH 8- and 10-bacteria while no difference was observed in phospholipid composition."}
{"id": "PMID:9044", "title": "[Mg dependence and other properties of fructose-1, 6-diphosphatase and glucose-6-phosphatase in various organs of cattle].", "content": "The properties of fructose-1.6-disphosphatase in supernatant of homogenate of liver, kidneys, and adductor muscles of cattle were tested. EDTA was found to activate the enzyme up to concentrations of 10 mMol. The pH optimum was 7.5 in the presence of EDTA. Even lower concentrations of magnesium ions caused activation of the enzyme, but an activating effect was obtained as well from relatively high Mg concentrations. Fructose-1.6-diphosphatase could by activated also by 0.2 mMol Mn or Co ions or 1 mMol Zn ions. Inhibitive action was obtained from Cu, Cd, Pb, and Hg ions. Microsomal fractions of cattle liver and kidney caused high activity of glucose-6-phosphatase, but only low action was obtained be using microsomal fractions of mesenteric mucous membrane or brain. Mg ions, basically, failed to trigger activation, and higher concentrations even caused inhibition. The relatively high activity of both fructose-1.6-diphosphatase and glucose-6-phosphatase in kidney of cattle appeared to suggest an involvement of those enzymes in gluconeogenesis.", "contents": "[Mg dependence and other properties of fructose-1, 6-diphosphatase and glucose-6-phosphatase in various organs of cattle]. The properties of fructose-1.6-disphosphatase in supernatant of homogenate of liver, kidneys, and adductor muscles of cattle were tested. EDTA was found to activate the enzyme up to concentrations of 10 mMol. The pH optimum was 7.5 in the presence of EDTA. Even lower concentrations of magnesium ions caused activation of the enzyme, but an activating effect was obtained as well from relatively high Mg concentrations. Fructose-1.6-diphosphatase could by activated also by 0.2 mMol Mn or Co ions or 1 mMol Zn ions. Inhibitive action was obtained from Cu, Cd, Pb, and Hg ions. Microsomal fractions of cattle liver and kidney caused high activity of glucose-6-phosphatase, but only low action was obtained be using microsomal fractions of mesenteric mucous membrane or brain. Mg ions, basically, failed to trigger activation, and higher concentrations even caused inhibition. The relatively high activity of both fructose-1.6-diphosphatase and glucose-6-phosphatase in kidney of cattle appeared to suggest an involvement of those enzymes in gluconeogenesis."}
{"id": "PMID:9045", "title": "Specific gamma-glutamyl transpeptidase inhibitor from human and animal intestines.", "content": "An inhibitor of gamma-glutamyl transpeptidase in human and animal intestines was assayed by means of a new method. In mice fed with LSM fodder, accumulation of the inhibitor in the mucous membrane of the small intestine was observed. Purified gamma-glutamyl transpeptidase inhibitor from mouse and human intestines was identified as L-serine. Neither this amino acid nor purifed inhibitor acted on other intestinal peptidases. Presumably, one of the ingredients of LSM feed influences accumulation of the inhibitor, and consequently diminishes absorption of gamma-glutamyl substrates in the intestine.", "contents": "Specific gamma-glutamyl transpeptidase inhibitor from human and animal intestines. An inhibitor of gamma-glutamyl transpeptidase in human and animal intestines was assayed by means of a new method. In mice fed with LSM fodder, accumulation of the inhibitor in the mucous membrane of the small intestine was observed. Purified gamma-glutamyl transpeptidase inhibitor from mouse and human intestines was identified as L-serine. Neither this amino acid nor purifed inhibitor acted on other intestinal peptidases. Presumably, one of the ingredients of LSM feed influences accumulation of the inhibitor, and consequently diminishes absorption of gamma-glutamyl substrates in the intestine."}
{"id": "PMID:9046", "title": "Specificity and inhibition of gamma-glutamyl transpeptidase in guinea pig intestines.", "content": "Gamma-Glutamyl transpeptidase activity in guinea pig intestine was tested toward 8 monoglutamyl and 4 diglutamyl substrates. Distinct differences in specificity and activity related to ontogenetic development were noted. A mixture of L-serine and borate inhibited specifically gamma-glutamyl transpeptidase activity of homogenates and accumulation of naphthylamine and 14C-substances in slices of intestine incubated with gamma-L-14C-glutamyl-alpha-naphthylamide. The same mixture, administered per os together with 14C-gamma-glutamyl substrate, specifically inhibited urinary excretion of 14C-substance, but had no effect on the rate of excretion of glycine, L-glutamic acid or L-pyroglutamic acid.", "contents": "Specificity and inhibition of gamma-glutamyl transpeptidase in guinea pig intestines. Gamma-Glutamyl transpeptidase activity in guinea pig intestine was tested toward 8 monoglutamyl and 4 diglutamyl substrates. Distinct differences in specificity and activity related to ontogenetic development were noted. A mixture of L-serine and borate inhibited specifically gamma-glutamyl transpeptidase activity of homogenates and accumulation of naphthylamine and 14C-substances in slices of intestine incubated with gamma-L-14C-glutamyl-alpha-naphthylamide. The same mixture, administered per os together with 14C-gamma-glutamyl substrate, specifically inhibited urinary excretion of 14C-substance, but had no effect on the rate of excretion of glycine, L-glutamic acid or L-pyroglutamic acid."}
{"id": "PMID:9049", "title": "Simultaneous determination of glutethimide, methyprylon, and methaqualone in serum by gas liquid chromatography.", "content": "A gas chromatographic method is described that permits the simultaneous determination of glutethimide, methyprylon, and methaqualone in serum samples. The threshold of sensitivity for each of the three hypnotics is 0.2 mg/1.", "contents": "Simultaneous determination of glutethimide, methyprylon, and methaqualone in serum by gas liquid chromatography. A gas chromatographic method is described that permits the simultaneous determination of glutethimide, methyprylon, and methaqualone in serum samples. The threshold of sensitivity for each of the three hypnotics is 0.2 mg/1."}
{"id": "PMID:9050", "title": "Determination of lorazepam in plasma by electron capture GLC.", "content": "A method is described for the determination of lorazepam plasma levels involving extraction from the sample and analysis of the intact lorazepam by electron capture gas-liquid chromatography. Using mass spectrometry it is demonstrated, that lorazepam shows a thermal rearrangement under gas chromatographic conditions. The limit of detection is 0.01 mg/l and the assay shows a linearity from 0.01-0.80 mg lorazepam per liter of plasma.", "contents": "Determination of lorazepam in plasma by electron capture GLC. A method is described for the determination of lorazepam plasma levels involving extraction from the sample and analysis of the intact lorazepam by electron capture gas-liquid chromatography. Using mass spectrometry it is demonstrated, that lorazepam shows a thermal rearrangement under gas chromatographic conditions. The limit of detection is 0.01 mg/l and the assay shows a linearity from 0.01-0.80 mg lorazepam per liter of plasma."}
{"id": "PMID:9051", "title": "[Structure of bromine containing metabolites of carbromal (author's transl)].", "content": "Isolation of three bromine containing metabolites from human urine is described and their chemical structure is proved by comparison of their physical properties with those of synthetically prepared substances. 2-Bromo-2-ethyl-butyramide, a pharmacologically active product, is showed to be the most important bromine containing metabolite by volume. In 3-position hydroxylated metabolites of carbromal, 3-hydroxy-carbromal and 2-Bromo-2-ethyl-3-hydroxy-butyramide have same physical properties as the synthesized DL-threo--diastereomeres.", "contents": "[Structure of bromine containing metabolites of carbromal (author's transl)]. Isolation of three bromine containing metabolites from human urine is described and their chemical structure is proved by comparison of their physical properties with those of synthetically prepared substances. 2-Bromo-2-ethyl-butyramide, a pharmacologically active product, is showed to be the most important bromine containing metabolite by volume. In 3-position hydroxylated metabolites of carbromal, 3-hydroxy-carbromal and 2-Bromo-2-ethyl-3-hydroxy-butyramide have same physical properties as the synthesized DL-threo--diastereomeres."}
{"id": "PMID:9052", "title": "Some properties of togavirus hemagglutinin studied with the aid of kaolin-adsorbed virus.", "content": "Acidification (at pH 5.75) of Semliki Forest virus and West Nile virus suspensions completely eliminated their hemagglutinating activity within several minutes, but did not affect their infectivity or change their ability to absorb homologous hemagglutination-inhibition antibodies. In order to assay antibody absorption it was necessary to remove all of the immune complex from the reaction mixture, because the immune complex inhibited additional hemagglutinin. Removal of the immune complex can be accomplished by the use of kaolin-absorbed virus. This procedure is simple and dependable and has been carried out with viruses from several groups--Toga-, Myxo-, Paramyxo- and Picornaviridae.", "contents": "Some properties of togavirus hemagglutinin studied with the aid of kaolin-adsorbed virus. Acidification (at pH 5.75) of Semliki Forest virus and West Nile virus suspensions completely eliminated their hemagglutinating activity within several minutes, but did not affect their infectivity or change their ability to absorb homologous hemagglutination-inhibition antibodies. In order to assay antibody absorption it was necessary to remove all of the immune complex from the reaction mixture, because the immune complex inhibited additional hemagglutinin. Removal of the immune complex can be accomplished by the use of kaolin-absorbed virus. This procedure is simple and dependable and has been carried out with viruses from several groups--Toga-, Myxo-, Paramyxo- and Picornaviridae."}
{"id": "PMID:9062", "title": "Pyridine nucleotide metabolism in imaginal discs of Drosophila melanogaster.", "content": "The pyridine nucleotide metabolism of imaginal discs of Drosophila melanogaster has been studied in vitro by incubating discs with labeled nicotinic acid in the presence and absence of ecdysterone. The major labeled compounds found within the discs are NAD, NADP, and nicotinic acid. There is preferential uptake of nicotinamide over nicotinic acid, although the Priess-Handler pathway is used exclusively. The presence of ecdysterone produces a small increase in the NADP/NAD ratio, and an increase in NAD synthesis, probably to compensate for increased NAD turnover.", "contents": "Pyridine nucleotide metabolism in imaginal discs of Drosophila melanogaster. The pyridine nucleotide metabolism of imaginal discs of Drosophila melanogaster has been studied in vitro by incubating discs with labeled nicotinic acid in the presence and absence of ecdysterone. The major labeled compounds found within the discs are NAD, NADP, and nicotinic acid. There is preferential uptake of nicotinamide over nicotinic acid, although the Priess-Handler pathway is used exclusively. The presence of ecdysterone produces a small increase in the NADP/NAD ratio, and an increase in NAD synthesis, probably to compensate for increased NAD turnover."}
{"id": "PMID:9063", "title": "Glucose 6-phosphate dehydrogenase in rainbow trout.", "content": "Electrophoretic analysis of glucose 6-phosphate dehydrogenase from liver and blood of rainbow trout revealed a complex series of bands, which could differ between fish. The partial interconvertible nature of these bands was demonstrated with enzyme that had been incompletely inactivated at pH 8.4. In a single population of 40 fish, a homozygote and a heterozygote for an electrophoretic variant allele were found. We suggest that G6PD in rainbow trout liver and blood is determinted  by two alleles at a single locus, with posttranslational modification responsible for the complex electrophoretic patterns seen. The basis for this variation appears to be NADH binding to the protein molecule. Another variant and other properties of the enzyme are described.", "contents": "Glucose 6-phosphate dehydrogenase in rainbow trout. Electrophoretic analysis of glucose 6-phosphate dehydrogenase from liver and blood of rainbow trout revealed a complex series of bands, which could differ between fish. The partial interconvertible nature of these bands was demonstrated with enzyme that had been incompletely inactivated at pH 8.4. In a single population of 40 fish, a homozygote and a heterozygote for an electrophoretic variant allele were found. We suggest that G6PD in rainbow trout liver and blood is determinted  by two alleles at a single locus, with posttranslational modification responsible for the complex electrophoretic patterns seen. The basis for this variation appears to be NADH binding to the protein molecule. Another variant and other properties of the enzyme are described."}
{"id": "PMID:9064", "title": "Protein chromatography on adsorbents with hydrophobic and ionic groups. Chromatography of dodecyl sulphate-solubilized proteins of the human erythrocyte membrane on N-(3-carboxypropionyl)aminodecyl-sepharose.", "content": "Human erythrocyte 'ghosts' were solubilized in 0.5% (w/v) sodium dodecyl sulphate at pH 4.0(I = 0.012 mol/I). At a loading of 1-2 mg of protein/ml of column volume, all of membrane proteins were adsorbed to a column of CPAD [N-(3-carboxypropionyl)-aminodecyl]-Sepharose at pH 4.0 (I = 0-012 mol/1) and room temperature (22 degrees C). Many proteins were subsequently desorbed by raising the pH or by including sodium dodecyl sulphate continuously in the eluting buffer. Experiments with a series of adsorbents homologous with CPAD-Sepharose, in which the length of the hydrocarbon chain was varied, provided strong evidence of hydrophobic interactions, in addition to ionic interactions, in the binding of these proteins to CPAD-Sepharose. Elution with increasing-pH gradients at different concentrations of sodium dodecyl sulphate showed that glycophorin (the major sialoglycoprotein) was eluted in the void volume, at recoveries close to 100%, when the detergent concentration was greater than or equal to 0.3% (w/v). Protein E, the major protein, was desorbed late in the pH gradient even at a high (0.5%, w/v) concentration of the detergent, and was always incompletely desorbed, the maximum recovery recorded being 40%. Spectrin (the high-molecular-weight polypeptide pair) did not behave in a well-defined manner, and was found widely distributed among the effluent fractions under all the conditions that were tested.", "contents": "Protein chromatography on adsorbents with hydrophobic and ionic groups. Chromatography of dodecyl sulphate-solubilized proteins of the human erythrocyte membrane on N-(3-carboxypropionyl)aminodecyl-sepharose. Human erythrocyte 'ghosts' were solubilized in 0.5% (w/v) sodium dodecyl sulphate at pH 4.0(I = 0.012 mol/I). At a loading of 1-2 mg of protein/ml of column volume, all of membrane proteins were adsorbed to a column of CPAD [N-(3-carboxypropionyl)-aminodecyl]-Sepharose at pH 4.0 (I = 0-012 mol/1) and room temperature (22 degrees C). Many proteins were subsequently desorbed by raising the pH or by including sodium dodecyl sulphate continuously in the eluting buffer. Experiments with a series of adsorbents homologous with CPAD-Sepharose, in which the length of the hydrocarbon chain was varied, provided strong evidence of hydrophobic interactions, in addition to ionic interactions, in the binding of these proteins to CPAD-Sepharose. Elution with increasing-pH gradients at different concentrations of sodium dodecyl sulphate showed that glycophorin (the major sialoglycoprotein) was eluted in the void volume, at recoveries close to 100%, when the detergent concentration was greater than or equal to 0.3% (w/v). Protein E, the major protein, was desorbed late in the pH gradient even at a high (0.5%, w/v) concentration of the detergent, and was always incompletely desorbed, the maximum recovery recorded being 40%. Spectrin (the high-molecular-weight polypeptide pair) did not behave in a well-defined manner, and was found widely distributed among the effluent fractions under all the conditions that were tested."}
{"id": "PMID:9065", "title": "The nature of the residual alpha-mannosidase in plasma in bovine mannosidosis.", "content": "Acidic alpha-mannosidase (EC 3.2.1.24), optimum pH 4.25, is absent from the plasma of Angus calves with mannosidosis, and the residual alpha-mannosidase activity has an optimum pH of 5.5, intermediate between that of the acidic and neutral alpha-mannosidases. This 'intermediate' alpha-mannosidase differs from the acidic form in its kinetic properties, its lack of marked inhibition by EDTA and its thermolability at 55 degrees C and physiological pH. Isoelectric focusing and ion-exchange chromatography show that it exists in at least two forms. The presence of a secondary peak at pH 5.5 in the pH/activity profile of normal plasma and the effect of heating at 55 degrees C indicate that such a form is present in normal plasma. The residual activity in the plasma of a calf with mannosidosis is therefore probably not the product of the defective gene. A differential assay, based on their different stabilities at 55 degrees C, has been developed for measuring the acidic and intermediate alpha-mannosidases in plasma. There was no correlation between the concentrations of the two enzymes in the plasma of Angus cows heterozygous for mannosidosis or in the plasma of normal animals. This precludes the use of the intermediate form as a reference enzyme for the acidic activity in a test for heterozygosity for mannosidosis based on the gene-dosage phenomenon. The concentrations of the intermediate activity were comparable in normal animals and animals homozygous or heterozygous for mannosidosis.", "contents": "The nature of the residual alpha-mannosidase in plasma in bovine mannosidosis. Acidic alpha-mannosidase (EC 3.2.1.24), optimum pH 4.25, is absent from the plasma of Angus calves with mannosidosis, and the residual alpha-mannosidase activity has an optimum pH of 5.5, intermediate between that of the acidic and neutral alpha-mannosidases. This 'intermediate' alpha-mannosidase differs from the acidic form in its kinetic properties, its lack of marked inhibition by EDTA and its thermolability at 55 degrees C and physiological pH. Isoelectric focusing and ion-exchange chromatography show that it exists in at least two forms. The presence of a secondary peak at pH 5.5 in the pH/activity profile of normal plasma and the effect of heating at 55 degrees C indicate that such a form is present in normal plasma. The residual activity in the plasma of a calf with mannosidosis is therefore probably not the product of the defective gene. A differential assay, based on their different stabilities at 55 degrees C, has been developed for measuring the acidic and intermediate alpha-mannosidases in plasma. There was no correlation between the concentrations of the two enzymes in the plasma of Angus cows heterozygous for mannosidosis or in the plasma of normal animals. This precludes the use of the intermediate form as a reference enzyme for the acidic activity in a test for heterozygosity for mannosidosis based on the gene-dosage phenomenon. The concentrations of the intermediate activity were comparable in normal animals and animals homozygous or heterozygous for mannosidosis."}
{"id": "PMID:9066", "title": "Iron-dependent binding of 8-anilinonaphthalene-1-sulphonate by both lactoferrin and transferrin.", "content": "Fluorescence of 8-anilinonaphthalene-1-sulphonate is enhanced by both lactoferrin and transferrin. The enhancement is relatively low between pH 4 and 8, and high at below pH 4. At physiological pH the fluorescence enhancement is higher with the iron-deprived than with the iron-saturated proteins. Binding of iron by lactoferrin is associated with lowering affinity for the dye.", "contents": "Iron-dependent binding of 8-anilinonaphthalene-1-sulphonate by both lactoferrin and transferrin. Fluorescence of 8-anilinonaphthalene-1-sulphonate is enhanced by both lactoferrin and transferrin. The enhancement is relatively low between pH 4 and 8, and high at below pH 4. At physiological pH the fluorescence enhancement is higher with the iron-deprived than with the iron-saturated proteins. Binding of iron by lactoferrin is associated with lowering affinity for the dye."}
{"id": "PMID:9067", "title": "The kinetics of formation of horseradish peroxidase compound I by reaction with peroxobenzoic acids. pH and peroxo acid substituent effects.", "content": "1. The kinetics of formation of horseradish peroxidase Compound I were studied by using peroxobenzoic acid and ten substituted peroxobenzoic acids as substrates. Kinetic data for the formation of Compound I with H2O2 and for the reaction of deuteroferrihaem with H2O2 and peroxobenzoic acids, to form a peroxidatically active intermediate, are included for comparison. 2. The observed second-order rate constants for the formation of Compound I with peroxobenzoic acids decrease with increasing pH, in the range pH 5-10, in contrast with pH-independence of the reaction with H2O2. The results imply that the formation of Compound I involves a reaction between the enzyme and un-ionized hydroperoxide molecules. 3. The maximal rate constants for Compound I formation with unhindered peroxobenzoic acids exceed that for H2O2. Peroxobenzoic acids with bulky ortho substituents show marked adverse steric effects. The pattern of substituent effects does not agree with expectations for an electrophilic oxidation of the enzyme by peroxoacid molecules in aqueous solution, but is in agreement with that expected for a reaction involving nucleophilic attack by peroxo anions. 4. Possible reaction mechanisms are considered by which the apparent conflict between the pH-effect and substituent-effect data may be resolved. A model in which it is postulated that a negatively charged 'electrostatic gate' controls access of substrate to the active site and may also activate substrate within the active site, provides the most satisfactory explanation for both the present results and data from the literature.", "contents": "The kinetics of formation of horseradish peroxidase compound I by reaction with peroxobenzoic acids. pH and peroxo acid substituent effects. 1. The kinetics of formation of horseradish peroxidase Compound I were studied by using peroxobenzoic acid and ten substituted peroxobenzoic acids as substrates. Kinetic data for the formation of Compound I with H2O2 and for the reaction of deuteroferrihaem with H2O2 and peroxobenzoic acids, to form a peroxidatically active intermediate, are included for comparison. 2. The observed second-order rate constants for the formation of Compound I with peroxobenzoic acids decrease with increasing pH, in the range pH 5-10, in contrast with pH-independence of the reaction with H2O2. The results imply that the formation of Compound I involves a reaction between the enzyme and un-ionized hydroperoxide molecules. 3. The maximal rate constants for Compound I formation with unhindered peroxobenzoic acids exceed that for H2O2. Peroxobenzoic acids with bulky ortho substituents show marked adverse steric effects. The pattern of substituent effects does not agree with expectations for an electrophilic oxidation of the enzyme by peroxoacid molecules in aqueous solution, but is in agreement with that expected for a reaction involving nucleophilic attack by peroxo anions. 4. Possible reaction mechanisms are considered by which the apparent conflict between the pH-effect and substituent-effect data may be resolved. A model in which it is postulated that a negatively charged 'electrostatic gate' controls access of substrate to the active site and may also activate substrate within the active site, provides the most satisfactory explanation for both the present results and data from the literature."}
{"id": "PMID:9068", "title": "Preparation of immobilized baker's-yeast glucose 6-phosphate dehydrogenase attached to modified sepharose and sephadex and a comparison of the properties of these preparations with those of the soluble enzyme.", "content": "1. Glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate-NADP+ oxidoreductase, EC 1.1.1.49) from baker's yeast (Saccharomyces cerevisiae) was immobilized on CNBr-activated Sepharose 4B with retention of about 3% of enzyme activity. This uncharged preparation was stable for up to 4 months when stored in borate buffer, pH7.6, at 4 degrees C. 2. Stable enzyme preparations with negative or positive overall charge were made by adding valine or ethylenediamine to the CNBr-activated Sepharose 4B 30min after addition of the enzyme. 3. These three immobilized enzyme preparations retained 40-60% of their activity after 15 min at 50 degrees C. The soluble enzyme is inactivated by these conditions. 4. The soluble enzyme lost 45 and 100% of its activity on incubation for 3h at pH6 and 10 respectively. The three immobilized-enzyme preparations were completely stable over this entire pH range. 5. The pH optimum of the positively and negatively charged immobilized-enzyme preparations were about 8 and 9 respectively. The soluble enzyme and the uncharged immobilized enzyme had an optimum pH at about 8.5 6. Glucose 6-phosphate dehydrogenase immobilized on CNBr-activated Sephadex G-25 was unstable, as was enzyme attached to CNBr-activated Sepharose 4B to which glycine, asparitic acid, valine or ethylenediamine was added at the same time as the enzyme.", "contents": "Preparation of immobilized baker's-yeast glucose 6-phosphate dehydrogenase attached to modified sepharose and sephadex and a comparison of the properties of these preparations with those of the soluble enzyme. 1. Glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate-NADP+ oxidoreductase, EC 1.1.1.49) from baker's yeast (Saccharomyces cerevisiae) was immobilized on CNBr-activated Sepharose 4B with retention of about 3% of enzyme activity. This uncharged preparation was stable for up to 4 months when stored in borate buffer, pH7.6, at 4 degrees C. 2. Stable enzyme preparations with negative or positive overall charge were made by adding valine or ethylenediamine to the CNBr-activated Sepharose 4B 30min after addition of the enzyme. 3. These three immobilized enzyme preparations retained 40-60% of their activity after 15 min at 50 degrees C. The soluble enzyme is inactivated by these conditions. 4. The soluble enzyme lost 45 and 100% of its activity on incubation for 3h at pH6 and 10 respectively. The three immobilized-enzyme preparations were completely stable over this entire pH range. 5. The pH optimum of the positively and negatively charged immobilized-enzyme preparations were about 8 and 9 respectively. The soluble enzyme and the uncharged immobilized enzyme had an optimum pH at about 8.5 6. Glucose 6-phosphate dehydrogenase immobilized on CNBr-activated Sephadex G-25 was unstable, as was enzyme attached to CNBr-activated Sepharose 4B to which glycine, asparitic acid, valine or ethylenediamine was added at the same time as the enzyme."}
{"id": "PMID:9069", "title": "Isolation and characterization of human plasma alpha 1-proteinase inhibitor and a conformational study of its interaction with proteinases.", "content": "1. alpha 1-Proteinase inhibitor was isolated from human plasma by a five-step procedure. Isoelectric focusing showed that six components focused between pH4.85 and 4.95. 2. The mol.wt. of the inhibitor was 52000 by sedimentation equilibrium and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The amino acid and carbohydrate compositions of the inhibitor were also determined. 3. The far-u.v.c.d. (circular-dichroism) spectrum indicated that the inhibitor had about 36% alpha-helical content. 4. The loss of proteinase-inhibitory activity when the inhibitor was exposed to pH values less than 5.0 or greater than 10.5 was accompanied by small changes in the far-u.v.c.d. spectrum and large changes in the near-u.v.c.d. spectrum. The change at alkaline pH was associated with ionization of tyrosine residues. 5. Interaction of inhibitor with chymotrypsin caused perturbation of the c.d. spectrum and this was used to follow the interaction and show a 1:1 stoicheiometry. 6. C.d., electrophoresis and isoelectric focusing showed that the inhibitor-enzyme complex is degraded by free enzyme. 7. Parallel studies with trypsin indicated that it too forms a 1:1 complex with inhibitor and is degraded by excess of enzyme.", "contents": "Isolation and characterization of human plasma alpha 1-proteinase inhibitor and a conformational study of its interaction with proteinases. 1. alpha 1-Proteinase inhibitor was isolated from human plasma by a five-step procedure. Isoelectric focusing showed that six components focused between pH4.85 and 4.95. 2. The mol.wt. of the inhibitor was 52000 by sedimentation equilibrium and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The amino acid and carbohydrate compositions of the inhibitor were also determined. 3. The far-u.v.c.d. (circular-dichroism) spectrum indicated that the inhibitor had about 36% alpha-helical content. 4. The loss of proteinase-inhibitory activity when the inhibitor was exposed to pH values less than 5.0 or greater than 10.5 was accompanied by small changes in the far-u.v.c.d. spectrum and large changes in the near-u.v.c.d. spectrum. The change at alkaline pH was associated with ionization of tyrosine residues. 5. Interaction of inhibitor with chymotrypsin caused perturbation of the c.d. spectrum and this was used to follow the interaction and show a 1:1 stoicheiometry. 6. C.d., electrophoresis and isoelectric focusing showed that the inhibitor-enzyme complex is degraded by free enzyme. 7. Parallel studies with trypsin indicated that it too forms a 1:1 complex with inhibitor and is degraded by excess of enzyme."}
{"id": "PMID:9070", "title": "The beta-glucosidase in the gut contents of the snail Achatina achatina.", "content": "1. The enzyme beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) from the gut contents of active Achatina achatina exists in two molecular forms, beta-glucosidase C (mol.wt. about 82000) and D (mol.wt. about 41000). 2. Only the lower-molecular-weight species was found in the gut contents of aestivating snails or in extracts from their digestive glands and washed gut walls. 3. On re-activation of some aestivating snails, betion of ATP and Mg2+ to the isolated gut contents or to extracts from washed gut walls led to the formation of higher-molecular-weight forms of the enzyme, beta-glucosidase A (mol.wt. about 329000) and beta-glucosidase B (mol.wt. about 165000). 5. All these forms of the enzyme have similar pH optimum (pH 5.0-5.6). 6. The Michaelis constants (Km) and heat stability of the enzyme increased with increasing molecular complexity.", "contents": "The beta-glucosidase in the gut contents of the snail Achatina achatina. 1. The enzyme beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) from the gut contents of active Achatina achatina exists in two molecular forms, beta-glucosidase C (mol.wt. about 82000) and D (mol.wt. about 41000). 2. Only the lower-molecular-weight species was found in the gut contents of aestivating snails or in extracts from their digestive glands and washed gut walls. 3. On re-activation of some aestivating snails, betion of ATP and Mg2+ to the isolated gut contents or to extracts from washed gut walls led to the formation of higher-molecular-weight forms of the enzyme, beta-glucosidase A (mol.wt. about 329000) and beta-glucosidase B (mol.wt. about 165000). 5. All these forms of the enzyme have similar pH optimum (pH 5.0-5.6). 6. The Michaelis constants (Km) and heat stability of the enzyme increased with increasing molecular complexity."}
{"id": "PMID:9071", "title": "Kinetic mechanism from steady-state kinetics of the reaction catalysed by baker's-yeast glucose 6-phosphate dehydrogenase in solution and covalently attached to sepharose.", "content": "1. The reaction catalysed by glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate-NADP+ oxidoreductase, EC 1.1.1.49) from baker's yeast was studied in 42mM-glycylglycine buffer, pH7.4 at 25 degrees C, by initial-velocity studies and by the use of NADPH as a product inhibitor. 2. The reactions catalysed by both the soluble enzyme and a stable enzyme covalently attached to CNBr-activated Sepharose 4B probably follow an ordered reaction mechanism with NADP+ and NADPH as the leading reactants. 3. The kinetic constants obtained for the soluble enzyme lere: KNADP+m, 19 muM; KNADP+s, 23 muM; KNADPHs, 15 muM. Similar values were obtained for the immobilized enzyme. 4. The assay of the immobilized enzyme was done by using a micro packed-bed recirculation reactor, and the advantages of this technique are discussed.", "contents": "Kinetic mechanism from steady-state kinetics of the reaction catalysed by baker's-yeast glucose 6-phosphate dehydrogenase in solution and covalently attached to sepharose. 1. The reaction catalysed by glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate-NADP+ oxidoreductase, EC 1.1.1.49) from baker's yeast was studied in 42mM-glycylglycine buffer, pH7.4 at 25 degrees C, by initial-velocity studies and by the use of NADPH as a product inhibitor. 2. The reactions catalysed by both the soluble enzyme and a stable enzyme covalently attached to CNBr-activated Sepharose 4B probably follow an ordered reaction mechanism with NADP+ and NADPH as the leading reactants. 3. The kinetic constants obtained for the soluble enzyme lere: KNADP+m, 19 muM; KNADP+s, 23 muM; KNADPHs, 15 muM. Similar values were obtained for the immobilized enzyme. 4. The assay of the immobilized enzyme was done by using a micro packed-bed recirculation reactor, and the advantages of this technique are discussed."}
{"id": "PMID:9072", "title": "Kinetic studies on pantothenase from Pseudomonas fluorescens. Effects of pH on substrate and inhibitor binding.", "content": "The velocity of the pantothenase-catalysed hydrolysis of pantothenate was studied over pH5.5-9, and in the presence of oxalate or oxaloacetate as an inhibitor. The pH-dependence of the reaction can be described by a kinetic equation containing two ionizations of the enzyme, with one ionizable group located at the substrate-binding site, and the other at the inhibitor-binding site. The Km value of pantothenase to pantothenate depends on the buffer used, and phosphate tends to give somewhat lower values than other buffers. Km also depends on pH, the best activities being observed at basic pH values. The pH-independent Km is 7.6mM in phosphate buffer at 20 degrees C; the corresponding Kapp.m value at pH7 is 15 mM. The pK value of the ionizable group at the substrate-binding site was measured by two methods: from the pH-rate profile and from the pH-Km rofile. pK is 7.0 in phosphate buffer at 20 degrees C, ranging in various buffers between 6.9 and 7.3. The van't Hoff enthalpies of substrate binding and H+ ion binding were--14kJ/mol respectively. The inhibition by oxalate or oxaloacetate is of non-competitive type and depends on pH, the inhibitors being effective at acidic pH values. The pK value of the ionizable group at the inhibitor-binding site was derived from the measurements of the K1 values over the pH range 6-7.5. The pK value was 6.4 in oxaloacetate inhibition, the pH-independent K1 being 0.36mM, and the corresponding Kapp.m about 1.8mM at pH7. Phenylmethanesulphonyl fluoride was capable of inactivating pantothenase.", "contents": "Kinetic studies on pantothenase from Pseudomonas fluorescens. Effects of pH on substrate and inhibitor binding. The velocity of the pantothenase-catalysed hydrolysis of pantothenate was studied over pH5.5-9, and in the presence of oxalate or oxaloacetate as an inhibitor. The pH-dependence of the reaction can be described by a kinetic equation containing two ionizations of the enzyme, with one ionizable group located at the substrate-binding site, and the other at the inhibitor-binding site. The Km value of pantothenase to pantothenate depends on the buffer used, and phosphate tends to give somewhat lower values than other buffers. Km also depends on pH, the best activities being observed at basic pH values. The pH-independent Km is 7.6mM in phosphate buffer at 20 degrees C; the corresponding Kapp.m value at pH7 is 15 mM. The pK value of the ionizable group at the substrate-binding site was measured by two methods: from the pH-rate profile and from the pH-Km rofile. pK is 7.0 in phosphate buffer at 20 degrees C, ranging in various buffers between 6.9 and 7.3. The van't Hoff enthalpies of substrate binding and H+ ion binding were--14kJ/mol respectively. The inhibition by oxalate or oxaloacetate is of non-competitive type and depends on pH, the inhibitors being effective at acidic pH values. The pK value of the ionizable group at the inhibitor-binding site was derived from the measurements of the K1 values over the pH range 6-7.5. The pK value was 6.4 in oxaloacetate inhibition, the pH-independent K1 being 0.36mM, and the corresponding Kapp.m about 1.8mM at pH7. Phenylmethanesulphonyl fluoride was capable of inactivating pantothenase."}
{"id": "PMID:9073", "title": "The V-region sequence of the H chain from a third rabbit anti-pneumococcal antibody.", "content": "The amino acid sequence of the V (variable) region of the heavy (H) chain of rabbit antibody BS-1, raised against type III pneumococcal vaccine, is reported. Together with the sequence data of the V region of the light (L) chain previously determined [Jaton (1974a) Biochem. J. 141, 1-13], the present work completes the analysis of the V domain of the homogeneous antibody BS-1. The V domains (VL + VH regions) of this antibody are compared with those of two other anti-(type III) pneumococcal antibodies BS-5 and K-25 [Jaton (1975) Biochem. J. 147, 235-247]. Except for the second hypervariable section of the L chains, these antibodies have very different sequences in the hypervariable segments of the V domains. Within the third hypervariable region of the H chain, each antibody has a different length: BS-1 is three amino acids shorter than K-25 and two amino acids shorter than BS-5. When the sequences in that section are aligned for maximal homology, only two residues, glycine-97 and leucine-101, are common to the three antibodies. On the basis of the amino acid sequences of these three anti-pneumococcal antibodies, the results do not support the concept of a simple correlation between primary structure in the hypervariable sections (known to determine the shape of the combining site) and antigen-binding specificity.", "contents": "The V-region sequence of the H chain from a third rabbit anti-pneumococcal antibody. The amino acid sequence of the V (variable) region of the heavy (H) chain of rabbit antibody BS-1, raised against type III pneumococcal vaccine, is reported. Together with the sequence data of the V region of the light (L) chain previously determined [Jaton (1974a) Biochem. J. 141, 1-13], the present work completes the analysis of the V domain of the homogeneous antibody BS-1. The V domains (VL + VH regions) of this antibody are compared with those of two other anti-(type III) pneumococcal antibodies BS-5 and K-25 [Jaton (1975) Biochem. J. 147, 235-247]. Except for the second hypervariable section of the L chains, these antibodies have very different sequences in the hypervariable segments of the V domains. Within the third hypervariable region of the H chain, each antibody has a different length: BS-1 is three amino acids shorter than K-25 and two amino acids shorter than BS-5. When the sequences in that section are aligned for maximal homology, only two residues, glycine-97 and leucine-101, are common to the three antibodies. On the basis of the amino acid sequences of these three anti-pneumococcal antibodies, the results do not support the concept of a simple correlation between primary structure in the hypervariable sections (known to determine the shape of the combining site) and antigen-binding specificity."}
{"id": "PMID:9074", "title": "Subcellular localization of a rat liver enzyme converting thyroxine into tri-iodothyronine and possible involvement of essential thiol groups.", "content": "Experiments with rat liver homogenates showed that on subcellular fractionation the ability to catalyse the conversion of thyroxine into tri-iodothyronine was lost. The activity could in part be restored by addition of the cytosol to the microsomal fraction. Both components were found to be heat labile. The necessity of the presence of cytosol could be circumvented by incorporation of thiol-group-containing compounds in the medium. Optimal enzymic activity was observed in the presence of dithiothreitol and EDTA in medium of low osmolarity. By comparing the distribution of the converting enzyme over the subcellular fractions with a microsomal marker enzyme, glucose 6-phosphatase, it was demonstrated that the former is indeed of microsomal origin. Finally, it was shown that thiol groups play an essential role in the conversion of thyroxine into tri-iodothyronine.", "contents": "Subcellular localization of a rat liver enzyme converting thyroxine into tri-iodothyronine and possible involvement of essential thiol groups. Experiments with rat liver homogenates showed that on subcellular fractionation the ability to catalyse the conversion of thyroxine into tri-iodothyronine was lost. The activity could in part be restored by addition of the cytosol to the microsomal fraction. Both components were found to be heat labile. The necessity of the presence of cytosol could be circumvented by incorporation of thiol-group-containing compounds in the medium. Optimal enzymic activity was observed in the presence of dithiothreitol and EDTA in medium of low osmolarity. By comparing the distribution of the converting enzyme over the subcellular fractions with a microsomal marker enzyme, glucose 6-phosphatase, it was demonstrated that the former is indeed of microsomal origin. Finally, it was shown that thiol groups play an essential role in the conversion of thyroxine into tri-iodothyronine."}
{"id": "PMID:9075", "title": "The interaction of reduced nicotinamide--adenine dinucleotide phosphate with reduced nicotinamide--adenine dinucleotide--ubiquinone reductase from bovine heart mitochondria.", "content": "Reduction of the chromophores of mitochondrial NADH-ubiquinone reductase by NADPH reaches only 50% of the extent of reduction by NADH, monitored at 450 nm. This effect is due to autoxidation of an enzyme component at a higher rate than its reduction by NADPH.", "contents": "The interaction of reduced nicotinamide--adenine dinucleotide phosphate with reduced nicotinamide--adenine dinucleotide--ubiquinone reductase from bovine heart mitochondria. Reduction of the chromophores of mitochondrial NADH-ubiquinone reductase by NADPH reaches only 50% of the extent of reduction by NADH, monitored at 450 nm. This effect is due to autoxidation of an enzyme component at a higher rate than its reduction by NADPH."}
{"id": "PMID:9076", "title": "Haemolysis induced by tyrosine crystals: Modifiers and inhibitors.", "content": "Tyrosine as a solid, but not in solution, caused human erythrocyte haemolysis. Haemolysis was increased with higher tyrosine concentrations and extended incubation times; it was greater at 37degrees than 4degreesC, and decreased by higher erythrocyte concentrations. Titration of phenolic groups on the surface of di-iodotyrosine crystals altered the extent of di-iodotyrosine-induced haemolysis. Haemolysis induced by tyrosine was inhibited by polyethylene glycol (mol.wt. 6000 or 20000) in a competitive fashion; polyoxyethylene/polyoxypropylene non-ionic detergents, polyvinylpyrrolidone (mol.wt. 40000 or 360000), 0.25--1.0M-NaC1, 0.25--1.0 M-KC1 and 0.25 M-NaSCN also inhibited haemolysis. H+-ion donation from the phenolic groups of tyrosine is suggested as part of the mechanism of haemolysis. Non-ionic detergents may inhibit tyrosine-crystal-induced haemolysis by binding the phenolic groups at the surface of the crystal.", "contents": "Haemolysis induced by tyrosine crystals: Modifiers and inhibitors. Tyrosine as a solid, but not in solution, caused human erythrocyte haemolysis. Haemolysis was increased with higher tyrosine concentrations and extended incubation times; it was greater at 37degrees than 4degreesC, and decreased by higher erythrocyte concentrations. Titration of phenolic groups on the surface of di-iodotyrosine crystals altered the extent of di-iodotyrosine-induced haemolysis. Haemolysis induced by tyrosine was inhibited by polyethylene glycol (mol.wt. 6000 or 20000) in a competitive fashion; polyoxyethylene/polyoxypropylene non-ionic detergents, polyvinylpyrrolidone (mol.wt. 40000 or 360000), 0.25--1.0M-NaC1, 0.25--1.0 M-KC1 and 0.25 M-NaSCN also inhibited haemolysis. H+-ion donation from the phenolic groups of tyrosine is suggested as part of the mechanism of haemolysis. Non-ionic detergents may inhibit tyrosine-crystal-induced haemolysis by binding the phenolic groups at the surface of the crystal."}
{"id": "PMID:9077", "title": "Studies on the amino acid-incorporating activity of native rat liver rough membrane and that reconstituted in vitro.", "content": "The amino acid-incorporating activities of free polyribosomes, rough membranes and rough membranes reconstituted in vitro, derived from rat liver, were compared. The amino acid-incorporating activity of the two membrane fractions were very similar in their response towards changes in pH, Mg2+ concentration and temperature, but differed from the response of the amino acid-incorporating activity of free polyribosomes. Free polyribosomes irreversibly lost part of their amino acid-incorporating capacity after they had become bound to rough membrane, from which the original ribosomes had been removed. Ribonuclease activity present in the membrane fraction may be responsible for this loss.", "contents": "Studies on the amino acid-incorporating activity of native rat liver rough membrane and that reconstituted in vitro. The amino acid-incorporating activities of free polyribosomes, rough membranes and rough membranes reconstituted in vitro, derived from rat liver, were compared. The amino acid-incorporating activity of the two membrane fractions were very similar in their response towards changes in pH, Mg2+ concentration and temperature, but differed from the response of the amino acid-incorporating activity of free polyribosomes. Free polyribosomes irreversibly lost part of their amino acid-incorporating capacity after they had become bound to rough membrane, from which the original ribosomes had been removed. Ribonuclease activity present in the membrane fraction may be responsible for this loss."}
{"id": "PMID:9078", "title": "Species differences in the conjugation of 4-hydroxy-3-methoxyphenylethanol with glucuronic acid and sulphuric acid.", "content": "The biosynthesis of the glucuronide and sulphate conjugates of 4-hydroxy-3-methoxyphenylethanol was demonstrated in vitro by using the high-speed supernatant and microsomal fractions of liver respectively. These two conjugates were also produced simultaneously by using the post-mitochondrial fraction of rat, rabbit or guinea-pig liver. In contrast only the glucuronide was synthesized by human liver and only the sulphate by mouse and cat livers. Neither of these conjugates was formed by the kidney or the small or large intestine of the rat. A high sulphate-conjugating activity was observed in mouse kidney; the rate of sulphation of 4-hydroxy-3-methoxyphenylethanol with kidney homogenate and high-speed supernatant preparations was 1.8 times greater than with liver preparations. The sulpho-conjugates of 4-hydroxy-3-methoxyphenylethanol and 4-hydroxy-3-methoxy-phenylglycol were also formed by enzyme preparations of rabbit adrenal and rat brain; the glycol was the better substrate in the latter system. Mouse brain did not possess any sulphotransferase activity. For the conjugation of 4-hydroxy-3-methoxyphenylethanol by rabbit liver, the Km for UDP-glucuronic acid was 0.22 mM and that for Na2SO4 was 3.45 mM. The sulphotransferase has a greater affinity for 4-hydroxy-3-methoxyphenyl-ethanol than has glucuronyltransferase, as indicated by their respective Km values of 0.036 and 1.3 mM. It was concluded that sulphate conjugation of 4-hydroxy-3-methoxyphenylethanol predominates in most species of animals.", "contents": "Species differences in the conjugation of 4-hydroxy-3-methoxyphenylethanol with glucuronic acid and sulphuric acid. The biosynthesis of the glucuronide and sulphate conjugates of 4-hydroxy-3-methoxyphenylethanol was demonstrated in vitro by using the high-speed supernatant and microsomal fractions of liver respectively. These two conjugates were also produced simultaneously by using the post-mitochondrial fraction of rat, rabbit or guinea-pig liver. In contrast only the glucuronide was synthesized by human liver and only the sulphate by mouse and cat livers. Neither of these conjugates was formed by the kidney or the small or large intestine of the rat. A high sulphate-conjugating activity was observed in mouse kidney; the rate of sulphation of 4-hydroxy-3-methoxyphenylethanol with kidney homogenate and high-speed supernatant preparations was 1.8 times greater than with liver preparations. The sulpho-conjugates of 4-hydroxy-3-methoxyphenylethanol and 4-hydroxy-3-methoxy-phenylglycol were also formed by enzyme preparations of rabbit adrenal and rat brain; the glycol was the better substrate in the latter system. Mouse brain did not possess any sulphotransferase activity. For the conjugation of 4-hydroxy-3-methoxyphenylethanol by rabbit liver, the Km for UDP-glucuronic acid was 0.22 mM and that for Na2SO4 was 3.45 mM. The sulphotransferase has a greater affinity for 4-hydroxy-3-methoxyphenyl-ethanol than has glucuronyltransferase, as indicated by their respective Km values of 0.036 and 1.3 mM. It was concluded that sulphate conjugation of 4-hydroxy-3-methoxyphenylethanol predominates in most species of animals."}
{"id": "PMID:9079", "title": "Characterization of the binding of human growth hormone to microsomal membranes from rat liver.", "content": "The binding of 125I-labelled human growth hormone to the 100000g microsomal membrane fraction prepared from the livers of normal female rats was dependent on time, temperature, pH, membrane concentration and concentration of 125I-labelled human growth hormone. At 22 degrees C binding reached a steady state after 16h, with the mean maximal specific binding being 20% of the tracer initially added. Dissociation of 125I-labelled human growth hormone from the membranes, after addition of excess of unlabelled hormone, was relatively slow with a half-time greater than 24h. Only minor degradation of the 125I-labelled human growth hormone was observed during incubation with membranes for 16 or 25h at 22 degrees C. Similarly, no significant change in the ability of membranes to bind human growth hormone was evident after preincubation of the membranes for 16 or 25h. Specificity studies showed that up to 90% of the 125I-labelled human growth hormone bound could be displaced by 1 mug of unlabelled hormone. Ovine prolactin also showed considerable competition for the binding site. Non-primate growth-hormone preparations (ovine, bovine, porcine and rat) and non-related hormones (insulin, thyrotropin, lutropin and follitropin) all showed negligible competition. Scatchard analysis of the binding data was consistent with two classes of binding site with binding affinities of 0.64 X 10(10) +/- 0.2 X 10(10)M-1 and 0.03 X 10(10) +/- 0.007 X 10(10)M-1 and corresponding binding capacities of 98.4 +/- 10 fmol/mg of protein and 314.6 +/- 46.3 fmol/mg of protein. These studies provide data which, in general, are consistent with the criteria required for hormone-receptor interaction. However, proof of the thesis that the human-growth-hormone-binding sites in female rat liver represent physiological receptors must await the demonstration of a correlation between hormone binding and a biological response.", "contents": "Characterization of the binding of human growth hormone to microsomal membranes from rat liver. The binding of 125I-labelled human growth hormone to the 100000g microsomal membrane fraction prepared from the livers of normal female rats was dependent on time, temperature, pH, membrane concentration and concentration of 125I-labelled human growth hormone. At 22 degrees C binding reached a steady state after 16h, with the mean maximal specific binding being 20% of the tracer initially added. Dissociation of 125I-labelled human growth hormone from the membranes, after addition of excess of unlabelled hormone, was relatively slow with a half-time greater than 24h. Only minor degradation of the 125I-labelled human growth hormone was observed during incubation with membranes for 16 or 25h at 22 degrees C. Similarly, no significant change in the ability of membranes to bind human growth hormone was evident after preincubation of the membranes for 16 or 25h. Specificity studies showed that up to 90% of the 125I-labelled human growth hormone bound could be displaced by 1 mug of unlabelled hormone. Ovine prolactin also showed considerable competition for the binding site. Non-primate growth-hormone preparations (ovine, bovine, porcine and rat) and non-related hormones (insulin, thyrotropin, lutropin and follitropin) all showed negligible competition. Scatchard analysis of the binding data was consistent with two classes of binding site with binding affinities of 0.64 X 10(10) +/- 0.2 X 10(10)M-1 and 0.03 X 10(10) +/- 0.007 X 10(10)M-1 and corresponding binding capacities of 98.4 +/- 10 fmol/mg of protein and 314.6 +/- 46.3 fmol/mg of protein. These studies provide data which, in general, are consistent with the criteria required for hormone-receptor interaction. However, proof of the thesis that the human-growth-hormone-binding sites in female rat liver represent physiological receptors must await the demonstration of a correlation between hormone binding and a biological response."}
{"id": "PMID:9098", "title": "Some aspects in the pharmacology of diclonium bromide (2-(3,2-dichloroanilino)quinolizinium bromide). Part I: Antispasmodic action.", "content": "Diclonium bromide (EU-2972; 2-(3,4-dichloroanilino)quinolizinium bromide) was demonstrated to possess an effective, prolonged inhibitory action on contractions in response to stimuli or propulsive movements in the lower bowel of the dog. The compound's antagonism to contractile activity was greater in the distal colon than in the duodenum or upper bowel. Diclonium bromide was a nonselective antispasmodic but, unlike papaverine, caused profound antagonism against smooth muscle contractile responses to intrinsic motor neural excitation. The drug had weak specific anticholinergic action, but its lack of antagonistic effect on other cholinergic responses in this study indicates that the anticholinergic action contributes very little, if at all, to its overall antispasmodic effect. The compound has potential application in the treatment of spastic-colon disease.", "contents": "Some aspects in the pharmacology of diclonium bromide (2-(3,2-dichloroanilino)quinolizinium bromide). Part I: Antispasmodic action. Diclonium bromide (EU-2972; 2-(3,4-dichloroanilino)quinolizinium bromide) was demonstrated to possess an effective, prolonged inhibitory action on contractions in response to stimuli or propulsive movements in the lower bowel of the dog. The compound's antagonism to contractile activity was greater in the distal colon than in the duodenum or upper bowel. Diclonium bromide was a nonselective antispasmodic but, unlike papaverine, caused profound antagonism against smooth muscle contractile responses to intrinsic motor neural excitation. The drug had weak specific anticholinergic action, but its lack of antagonistic effect on other cholinergic responses in this study indicates that the anticholinergic action contributes very little, if at all, to its overall antispasmodic effect. The compound has potential application in the treatment of spastic-colon disease."}
{"id": "PMID:9099", "title": "[Antibacterial activity of sisomicin in comparison with gentamicin].", "content": "The antibacterial activity of sisomicin -- a new aminoglycoside antibiotic -- as compared with gentamicin was tested on 521 bacterial strains of different species in a serial-dilution test. Staphylococci, streptococci, E. coli, Klebsialla-Enterobacter, indole-psitive Proteus strains, pseufomonads, Salmonads, Salmonellae, and Serratia marcescens were inhibited to the extent of 100% at a maximun of 4.0 mug/ml. Sisomicin showed a higher antibacterial activity against part of the bacterial species. Gentamicin-resistant pseudomonads and Klebsiella (clinical isolates) were still inhibited to the extent of 42 and 67%, respectively, by sisomicin. In addition to the determination of the MIC values for the use of different liquid media, investigations on the determin ation of the minimal bactericidal concentration (MBC), the effect of serum, pH, and inoculum on the bacterial activity, and investigations on the resistance development in vitro were also carried out.", "contents": "[Antibacterial activity of sisomicin in comparison with gentamicin]. The antibacterial activity of sisomicin -- a new aminoglycoside antibiotic -- as compared with gentamicin was tested on 521 bacterial strains of different species in a serial-dilution test. Staphylococci, streptococci, E. coli, Klebsialla-Enterobacter, indole-psitive Proteus strains, pseufomonads, Salmonads, Salmonellae, and Serratia marcescens were inhibited to the extent of 100% at a maximun of 4.0 mug/ml. Sisomicin showed a higher antibacterial activity against part of the bacterial species. Gentamicin-resistant pseudomonads and Klebsiella (clinical isolates) were still inhibited to the extent of 42 and 67%, respectively, by sisomicin. In addition to the determination of the MIC values for the use of different liquid media, investigations on the determin ation of the minimal bactericidal concentration (MBC), the effect of serum, pH, and inoculum on the bacterial activity, and investigations on the resistance development in vitro were also carried out."}
{"id": "PMID:9096", "title": "Association between HLA and cutaneous necrotizing venulitis.", "content": "A group of patients has been identified with cutaneous necrotizing venulitis (vasculitis). These patients, some with concomitant connective tissue disorders, have skin lesions that  separate them from the arteritis commonly described as rheumatoid vasculitis. HLA typing has been performed on 31 of these unrelated patients with cutaneous necrotizing venulitis, including 19 with associated chronic disorders. The antigen pair A11, BW35 was found in 5 of these 19 patients and in 11 of 346 controls. This difference in frequency is statistically significant. Because HLA genes appear to be linked to immune response genes, these data suggest that such genes may exist in patients with this form of cutaneous necrotizing venulitis with associated connective tissue disease.", "contents": "Association between HLA and cutaneous necrotizing venulitis. A group of patients has been identified with cutaneous necrotizing venulitis (vasculitis). These patients, some with concomitant connective tissue disorders, have skin lesions that  separate them from the arteritis commonly described as rheumatoid vasculitis. HLA typing has been performed on 31 of these unrelated patients with cutaneous necrotizing venulitis, including 19 with associated chronic disorders. The antigen pair A11, BW35 was found in 5 of these 19 patients and in 11 of 346 controls. This difference in frequency is statistically significant. Because HLA genes appear to be linked to immune response genes, these data suggest that such genes may exist in patients with this form of cutaneous necrotizing venulitis with associated connective tissue disease."}
{"id": "PMID:9100", "title": "Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity.", "content": "A Vaccinium myrtillus anthocyanosides preparation (equivalent to 25% of anthocyanidins) demonstrated significant vasoprotective and antioedema properties in exerimental animals. In rabbits, the skin capillary permeability increase, due to chloroform, was reduced both after i.p. (25--100 mg/kg) and oral administration (200--400 mg/kg) of anthocyanosides. Their activity was more lasting in comparison to rutin or mepyramine and this did not seem to be due to a specific antagonism towards inflammatory process mediators such as histamine or bradykinin. Experiments carried out in rats demonstrated that Vacinium myrtillus anthocyanosides were effective both in skin capillary permeability test as well as on vascular resistance of rats fed a P factor deficient diet. In the former test effective doses were in the range of 25--100 mg/kg (by oral route). In both the animal species investigated, anthocyanosides were two-fold more active when compared to the flavonoid rutin. Vaccinium myrtillus anthocyanosides by oral route inhibited carrageein paw oedema in rats showing a dose-response relationship. An antioedema activity was detected also after i.v. or topical application.", "contents": "Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity. A Vaccinium myrtillus anthocyanosides preparation (equivalent to 25% of anthocyanidins) demonstrated significant vasoprotective and antioedema properties in exerimental animals. In rabbits, the skin capillary permeability increase, due to chloroform, was reduced both after i.p. (25--100 mg/kg) and oral administration (200--400 mg/kg) of anthocyanosides. Their activity was more lasting in comparison to rutin or mepyramine and this did not seem to be due to a specific antagonism towards inflammatory process mediators such as histamine or bradykinin. Experiments carried out in rats demonstrated that Vacinium myrtillus anthocyanosides were effective both in skin capillary permeability test as well as on vascular resistance of rats fed a P factor deficient diet. In the former test effective doses were in the range of 25--100 mg/kg (by oral route). In both the animal species investigated, anthocyanosides were two-fold more active when compared to the flavonoid rutin. Vaccinium myrtillus anthocyanosides by oral route inhibited carrageein paw oedema in rats showing a dose-response relationship. An antioedema activity was detected also after i.v. or topical application."}
{"id": "PMID:9101", "title": "Comparison of the action of BD 40 A and some other beta-adrenoceptor stimulants on the isolated trachea and atria of the guinea pig.", "content": "3-Formylamino-4-hydroxy-a-(N-1-methyl-2-p-methoxyphenethyl-aminomethyl)-benzylalcohol hemifumarate (BD 40A) was compared with isoproterenol, orciprenaline, trimetoquinol and salbutamol for its beta-adrenergic activity and selectivity in vitro. On trachea, the maximum relaxing responses to five agonists were similar, but the order of potency was BD 40A greater than trimetoquinol greater than isoproterenol greater than or equal to salbutamol greater than orciprenaline. On atria, the maximum chronotropic and inotropic responses to isoproterenol were greater than those to BD 40A, orciprenaline and trimetoquinol, and salbutamol caused the weakest cardiac stimulating effect. Namely, the latter four drugs appeared to be partial agonists on atria. Salbutamol showed the high selectivity for trachea, whereas orciprenaline and trimetoquinol were equipotent on trachea and atria. Isoproterenol was more potent on atria than on trachea. BD 40A had the highest bronchoselectivity among five agonists and seemed to act on the beta-adrenergic receptor directly.", "contents": "Comparison of the action of BD 40 A and some other beta-adrenoceptor stimulants on the isolated trachea and atria of the guinea pig. 3-Formylamino-4-hydroxy-a-(N-1-methyl-2-p-methoxyphenethyl-aminomethyl)-benzylalcohol hemifumarate (BD 40A) was compared with isoproterenol, orciprenaline, trimetoquinol and salbutamol for its beta-adrenergic activity and selectivity in vitro. On trachea, the maximum relaxing responses to five agonists were similar, but the order of potency was BD 40A greater than trimetoquinol greater than isoproterenol greater than or equal to salbutamol greater than orciprenaline. On atria, the maximum chronotropic and inotropic responses to isoproterenol were greater than those to BD 40A, orciprenaline and trimetoquinol, and salbutamol caused the weakest cardiac stimulating effect. Namely, the latter four drugs appeared to be partial agonists on atria. Salbutamol showed the high selectivity for trachea, whereas orciprenaline and trimetoquinol were equipotent on trachea and atria. Isoproterenol was more potent on atria than on trachea. BD 40A had the highest bronchoselectivity among five agonists and seemed to act on the beta-adrenergic receptor directly."}
{"id": "PMID:9102", "title": "The choice of neuroleptics in the treatment of schizophrenia: a critical review.", "content": "The selective use of different neuroleptics in the treatment of schizophrenia by some psychiatrist according to the greater need for a sedative, antidelusional or activating effect is supported only by some uncontrolled clinical observations. Most extensive controlled studies done until now showed no significant differences among neuroloptics in their therapeutic efficacy. The hypothesis that these drugs have specific and selective actions therfore cannot be accepted. In the single patient it seems more rational to choose the right dosage schedule instead of the \"right drug\". Though the study of the metabolism of these drugs remains the most interesting approach to the problem of the individualization of the therapy., the results of these studies have until now been disappointing e.g. plasma levels of chlorpromazine correlated weakly with clinical improvement. In clinical practice an important element in the process of choosing is still the incidence of side effects and in fact at the moment \"the drug of choice\" can only be the drug best tolerated by the patient.", "contents": "The choice of neuroleptics in the treatment of schizophrenia: a critical review. The selective use of different neuroleptics in the treatment of schizophrenia by some psychiatrist according to the greater need for a sedative, antidelusional or activating effect is supported only by some uncontrolled clinical observations. Most extensive controlled studies done until now showed no significant differences among neuroloptics in their therapeutic efficacy. The hypothesis that these drugs have specific and selective actions therfore cannot be accepted. In the single patient it seems more rational to choose the right dosage schedule instead of the \"right drug\". Though the study of the metabolism of these drugs remains the most interesting approach to the problem of the individualization of the therapy., the results of these studies have until now been disappointing e.g. plasma levels of chlorpromazine correlated weakly with clinical improvement. In clinical practice an important element in the process of choosing is still the incidence of side effects and in fact at the moment \"the drug of choice\" can only be the drug best tolerated by the patient."}
{"id": "PMID:9104", "title": "Interaction of psychotropic agents with central neurotransmitters as revealed by their effects on PGO waves in the cat.", "content": "One of the phasic phenomena of REM (rapid eye movement) sleep, the ponto-geniculo-occipital (PGO) waves, are induced in cats by either depleting brain monoamines with the benzoquinolizine derivative Ro 4-1284 or inhibiting the synthesis of 5-hydroxy-tryptamine (5-HT) by p-chlorophenylalanine (PCPA). The effects of the most important psychotropic agents on PGO1284 and PGOPCPA are reported and explained by their interaction with one or more of the 4 neurotransmitters known so far to be involved in the regulation of the PGO wave generation in the pontine reticular formation. Tricyclic antidepressants depress PGO waves by inhibiting the neuronal uptake of norepinephrine (NE) and/or 5-HT. Some neuroleptics increase the density of GO waves by blocking 5-HT and/or NE receptors. Various indole hallucinogens depress PGO waves by stimulating 5-HT receptors. Benzoldiazepines appear to enhance a (gamma-aminobutyric acid)-ergic (GABA)-ergic inhibitory influence on NE neurons and increase the density of PGO waves in the presence of functionally intact NE neurons.", "contents": "Interaction of psychotropic agents with central neurotransmitters as revealed by their effects on PGO waves in the cat. One of the phasic phenomena of REM (rapid eye movement) sleep, the ponto-geniculo-occipital (PGO) waves, are induced in cats by either depleting brain monoamines with the benzoquinolizine derivative Ro 4-1284 or inhibiting the synthesis of 5-hydroxy-tryptamine (5-HT) by p-chlorophenylalanine (PCPA). The effects of the most important psychotropic agents on PGO1284 and PGOPCPA are reported and explained by their interaction with one or more of the 4 neurotransmitters known so far to be involved in the regulation of the PGO wave generation in the pontine reticular formation. Tricyclic antidepressants depress PGO waves by inhibiting the neuronal uptake of norepinephrine (NE) and/or 5-HT. Some neuroleptics increase the density of GO waves by blocking 5-HT and/or NE receptors. Various indole hallucinogens depress PGO waves by stimulating 5-HT receptors. Benzoldiazepines appear to enhance a (gamma-aminobutyric acid)-ergic (GABA)-ergic inhibitory influence on NE neurons and increase the density of PGO waves in the presence of functionally intact NE neurons."}
{"id": "PMID:9105", "title": "[Proceedings: Psychotropic drugs and quality of sleep: quantitative neurophysiological and subjective parameters (author's transl)].", "content": "The effect of drugs of the 3 main psychopharmaceutical classes (anxiolytics, neuroleptics, antidepressants) on objective and subjective sleep parameters was studied in healthy normal volunteers. Objective parameters included: computerclassified sleep stages, visually evaluated REM-activity as well as 22 variables of the quantitatively analyzed all-night sleep and REM-sleep EEG. Alterations of the subjective sleep quality were rated based on a sleep self-rating scale. It was found that anxiolytics, neuroleptics and antidepressants induce characteristic changes in the objective sleep parameters. Subjectively, the quality of sleep was best after anxiolytics, while the quality of awakening in the morning was dependent on the dose of the anxiolytic drug. Finally, the relationship between objective and subjective sleep parameters was explored.", "contents": "[Proceedings: Psychotropic drugs and quality of sleep: quantitative neurophysiological and subjective parameters (author's transl)]. The effect of drugs of the 3 main psychopharmaceutical classes (anxiolytics, neuroleptics, antidepressants) on objective and subjective sleep parameters was studied in healthy normal volunteers. Objective parameters included: computerclassified sleep stages, visually evaluated REM-activity as well as 22 variables of the quantitatively analyzed all-night sleep and REM-sleep EEG. Alterations of the subjective sleep quality were rated based on a sleep self-rating scale. It was found that anxiolytics, neuroleptics and antidepressants induce characteristic changes in the objective sleep parameters. Subjectively, the quality of sleep was best after anxiolytics, while the quality of awakening in the morning was dependent on the dose of the anxiolytic drug. Finally, the relationship between objective and subjective sleep parameters was explored."}
{"id": "PMID:9107", "title": "[Interactions of dopamine receptor agonists and antagonists with regard to dopamine synthesis and metabolism].", "content": "Intraperitioneal injection of d-amphetamine sulfate, 0.3-3 mg/kg, led to a marked rise in dopa formation in the dopamine rich areas c. striatum and mesolibbic cortex of the rat brain inhibiton of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCL (NSD 1015). However, amphetamine given in a dose of 10 mg/kg decreased the tyrosine hydroxylation rate in the mesolimbic cortex as well as the norepinephrine containing neocortex. In combination with haloperidol the stimulating effect of the neuroleptic on dopa formation was markedly potentiated by amphetamine in rat forebrain. Also, amphetamine potentiated the haloperidol induced increase in dopamine release in vivo measured as 3-methoxytyramine formation. The functional antagonists haloperidol and d-amphetamine appear to have synergistic effects on dopaminergic neurons.", "contents": "[Interactions of dopamine receptor agonists and antagonists with regard to dopamine synthesis and metabolism]. Intraperitioneal injection of d-amphetamine sulfate, 0.3-3 mg/kg, led to a marked rise in dopa formation in the dopamine rich areas c. striatum and mesolibbic cortex of the rat brain inhibiton of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCL (NSD 1015). However, amphetamine given in a dose of 10 mg/kg decreased the tyrosine hydroxylation rate in the mesolimbic cortex as well as the norepinephrine containing neocortex. In combination with haloperidol the stimulating effect of the neuroleptic on dopa formation was markedly potentiated by amphetamine in rat forebrain. Also, amphetamine potentiated the haloperidol induced increase in dopamine release in vivo measured as 3-methoxytyramine formation. The functional antagonists haloperidol and d-amphetamine appear to have synergistic effects on dopaminergic neurons."}
{"id": "PMID:9108", "title": "[Acute and chronic effects of carpipramine, clozapine, haloperidol and sulpiride on the metabolism of biogenic amines in the rat brain (author's transl)].", "content": "In acute and chronic experiments investigations were made concerning the effect of clozapine, haloperidol, sulpiride and carpipramine on MHPG, HVA and 5-HIAA in rat brain and on motor activity of the animals. The activity of the rats treated with clozapine and haloperidol was reduced on the first day. After 10 days of treatment this effected of clozapine was significantly diminished. The MHPG level increased slightly on the first day of treatment with all four drugs. This elevation was maintained after chronic treatment with carpipramine and sulpiride, whereas clozapine and haloperidol decreased the MHPG content. 5-HIAA values did not show significant changes in acute experiments, whereas in chronic ones there was an increase. Haloperidol and clozapine induced a strong increase of HVA which decreased after 11 days in those animals treated with haloperidol. In comparison to haloperidol, after clozapine application the percentage of HVA-increase was higher in the limbic system than in the nigrostriatum.", "contents": "[Acute and chronic effects of carpipramine, clozapine, haloperidol and sulpiride on the metabolism of biogenic amines in the rat brain (author's transl)]. In acute and chronic experiments investigations were made concerning the effect of clozapine, haloperidol, sulpiride and carpipramine on MHPG, HVA and 5-HIAA in rat brain and on motor activity of the animals. The activity of the rats treated with clozapine and haloperidol was reduced on the first day. After 10 days of treatment this effected of clozapine was significantly diminished. The MHPG level increased slightly on the first day of treatment with all four drugs. This elevation was maintained after chronic treatment with carpipramine and sulpiride, whereas clozapine and haloperidol decreased the MHPG content. 5-HIAA values did not show significant changes in acute experiments, whereas in chronic ones there was an increase. Haloperidol and clozapine induced a strong increase of HVA which decreased after 11 days in those animals treated with haloperidol. In comparison to haloperidol, after clozapine application the percentage of HVA-increase was higher in the limbic system than in the nigrostriatum."}
{"id": "PMID:9109", "title": "Stimulation of rat striatal tyrosine hydroxylase by phospholipids and adenosine-3',5'-monophosphate.", "content": "Rat striatal tyrosine hydroxylase is stimulated in vitro by various phospholipids. This stimulation was produced by a 3- to 4-fold increase in affinity for pteridine cofactor. No change in the Km for tyrosine was observed, The sedimentation pattern of tyrosine hydroxylase on linear sucrose gradients showed no indication of enzyme dissociation in the presence of lysolecithin at maximal stimulatory concentration. Crude striatal tyrosine hydroxylase is also activated by a combination of ATP, Mg++, EGTA and cAMP. After removing these agents by Sephadex G-25 chromatography, the activated form of the enzyme can be further stimulated by lysolecithin. These results suggest a possible role for phospholipids in the regulation of striatal dopamine synthesis.", "contents": "Stimulation of rat striatal tyrosine hydroxylase by phospholipids and adenosine-3',5'-monophosphate. Rat striatal tyrosine hydroxylase is stimulated in vitro by various phospholipids. This stimulation was produced by a 3- to 4-fold increase in affinity for pteridine cofactor. No change in the Km for tyrosine was observed, The sedimentation pattern of tyrosine hydroxylase on linear sucrose gradients showed no indication of enzyme dissociation in the presence of lysolecithin at maximal stimulatory concentration. Crude striatal tyrosine hydroxylase is also activated by a combination of ATP, Mg++, EGTA and cAMP. After removing these agents by Sephadex G-25 chromatography, the activated form of the enzyme can be further stimulated by lysolecithin. These results suggest a possible role for phospholipids in the regulation of striatal dopamine synthesis."}
{"id": "PMID:9110", "title": "[Free description of drug effects and description by questionaire of a sleep inducer (flurazepam) by normal test subjects (author's transl)].", "content": "Giving flurazepam and placebo to students as subjects, the free description of drug-effects (FD) was compared to the description by a questionaire (QD). The results were: 1. The FD-method was more informative than the QD-method. 2. The FD-method induced less frequent placebo effects and more frequent verum-non-effects than did the QD-method. 3. The results (1) and (2) based mainly on the variables time-to fall-asleep, subjective quality of sleep and total time of sleep, in which variables flurazepam differed significantly from placebo.", "contents": "[Free description of drug effects and description by questionaire of a sleep inducer (flurazepam) by normal test subjects (author's transl)]. Giving flurazepam and placebo to students as subjects, the free description of drug-effects (FD) was compared to the description by a questionaire (QD). The results were: 1. The FD-method was more informative than the QD-method. 2. The FD-method induced less frequent placebo effects and more frequent verum-non-effects than did the QD-method. 3. The results (1) and (2) based mainly on the variables time-to fall-asleep, subjective quality of sleep and total time of sleep, in which variables flurazepam differed significantly from placebo."}
{"id": "PMID:9111", "title": "[Personality-specfic action of a tranquilizer (author's transl)].", "content": "23 emotionally lable and 22 emotionally stable subjects wefe selected from a total smaple of 147 students by three personality inventories (FPI, GT, MPI). In a 2(3)-factor design the following effects of a single dose of 1.5 mg bromazepam p.o. against placebo were found: whereas the fine-motor activity (tapping, line-tracing) was stabilized independently of personality traits, the performance in attention tests (d2, choice-reaction time) was decreased in the emotionally stable group. In the emotionally lable group, i.e. in those subjects for whom bromazepam could therapeutically be indicated, an advantageous effect on performance in these tests was possible. The following variables were not affected by personality or medication: after-image of spiral rotor, critical flicker fusion (CFF), taking-task", "contents": "[Personality-specfic action of a tranquilizer (author's transl)]. 23 emotionally lable and 22 emotionally stable subjects wefe selected from a total smaple of 147 students by three personality inventories (FPI, GT, MPI). In a 2(3)-factor design the following effects of a single dose of 1.5 mg bromazepam p.o. against placebo were found: whereas the fine-motor activity (tapping, line-tracing) was stabilized independently of personality traits, the performance in attention tests (d2, choice-reaction time) was decreased in the emotionally stable group. In the emotionally lable group, i.e. in those subjects for whom bromazepam could therapeutically be indicated, an advantageous effect on performance in these tests was possible. The following variables were not affected by personality or medication: after-image of spiral rotor, critical flicker fusion (CFF), taking-task"}
{"id": "PMID:9112", "title": "[Comparison of experimental-psychological and clinical findings on the effect of a test substance (author's transl)].", "content": "The results of a pharmacopsychological study on male students high or low in emotional stability are compared to those of a clinical study on neurotic out- and inpatients. These studies examine the effects of diazepam and various doses of a thienodiazepine (Bay g 5653), a drug under investigation. Although the studies are not completely comparable (placebo control missing in the clinical study, not enough information about comparable base line measures) the differences in effects of Bay g 5653 and diazepam on the actual emotional state, as measured by an adjective check list, show a certain amount of correspondence between normal subjects and patients but also considerable discrepancies.", "contents": "[Comparison of experimental-psychological and clinical findings on the effect of a test substance (author's transl)]. The results of a pharmacopsychological study on male students high or low in emotional stability are compared to those of a clinical study on neurotic out- and inpatients. These studies examine the effects of diazepam and various doses of a thienodiazepine (Bay g 5653), a drug under investigation. Although the studies are not completely comparable (placebo control missing in the clinical study, not enough information about comparable base line measures) the differences in effects of Bay g 5653 and diazepam on the actual emotional state, as measured by an adjective check list, show a certain amount of correspondence between normal subjects and patients but also considerable discrepancies."}
{"id": "PMID:9113", "title": "[Changes in drug elimination under the influence of perazine therapy (author's transl)].", "content": "In 8 male patients who were treated with perazine for a schizophrenic psychosis (200-800 mg/die), the elimination rate of phenazone was investigated. Simultaneously determinations of plasma levels of perazine and desmethylperazine were carried out. The average half-life of phenazone was 27.0 h in perazine-treated patients and 11.2 h in controls. Correspondingly, the clearance of phenazone decreased from 47.0 ml/min to 18.9 ml/min under perazine, both differences being highly significant. The amount of 4-OH-phenazone, the principal hydroxylated metabolite excreted in the urine, was 66 mg/24 h in the perazine group, and significantly different from the results obtained in the control group: 185 mg/24 h. In contrast the urinary excretion of the unchanged phenazone increased from 29 to 40 mg/24 h under perazine. The results are interpreted to demonstrate inhibition of drug hydroxylation in the liver by perazine treatment.", "contents": "[Changes in drug elimination under the influence of perazine therapy (author's transl)]. In 8 male patients who were treated with perazine for a schizophrenic psychosis (200-800 mg/die), the elimination rate of phenazone was investigated. Simultaneously determinations of plasma levels of perazine and desmethylperazine were carried out. The average half-life of phenazone was 27.0 h in perazine-treated patients and 11.2 h in controls. Correspondingly, the clearance of phenazone decreased from 47.0 ml/min to 18.9 ml/min under perazine, both differences being highly significant. The amount of 4-OH-phenazone, the principal hydroxylated metabolite excreted in the urine, was 66 mg/24 h in the perazine group, and significantly different from the results obtained in the control group: 185 mg/24 h. In contrast the urinary excretion of the unchanged phenazone increased from 29 to 40 mg/24 h under perazine. The results are interpreted to demonstrate inhibition of drug hydroxylation in the liver by perazine treatment."}
{"id": "PMID:9123", "title": "Porcine malignant hyperthermia. III: Adrenergic blockade.", "content": "The effects of the establishment of an adrenergic blockade on suxamethonium-induced porcine malignant hyperthermia (MH) were investigated in Pietrain pigs. Six animals were fed reserpine 10 mg daily for 7 days and then challenged with suxamethonium. Three survived but the remainder developed fatal MH. In a further study of 10 pigs, either phentolamine 40 mug/kg/min or propranolol 50 mug/kg/min were administered for 30 min before suxamethonium stimulation and continued for the duration of the experiment. The five year beta-blocked pigs all became hyperthermic and died whereas the phentolamine-treated group survived. However, both alpha adrenergic blockade and successful reserpinization failed to prevent the abnormal muscle response to the first dose of suxamethonium.", "contents": "Porcine malignant hyperthermia. III: Adrenergic blockade. The effects of the establishment of an adrenergic blockade on suxamethonium-induced porcine malignant hyperthermia (MH) were investigated in Pietrain pigs. Six animals were fed reserpine 10 mg daily for 7 days and then challenged with suxamethonium. Three survived but the remainder developed fatal MH. In a further study of 10 pigs, either phentolamine 40 mug/kg/min or propranolol 50 mug/kg/min were administered for 30 min before suxamethonium stimulation and continued for the duration of the experiment. The five year beta-blocked pigs all became hyperthermic and died whereas the phentolamine-treated group survived. However, both alpha adrenergic blockade and successful reserpinization failed to prevent the abnormal muscle response to the first dose of suxamethonium."}
{"id": "PMID:9118", "title": "[Organization and results of cadaver kidney transplantation from 1969 to 1973 (author's transl)].", "content": "France transplant was founded in order to organize rationally the cadaver kidneys transport and transplantation with is omogenous compatibility tests. 2143 hemodialysis patients have been presently (1-9-72) treated in 82 dialysis center in France; 964 of them are in the France Transplant waiting list. According with recent laws, nervous function cessation is synonimous of death. That made possible, by good resuscitation techniques, to maintain a good level of circulation and oxigenation of organs. Family permit is required for this purpose. 17 medical transporttion staffs are at work in 12 France towns and cooperate with 12 typing laboratoires working with the same techniques and reagents. One permanent secretariat in Paris is always telex connected with all staffs and mantains a continuous up to date patients waiting list. 415 cadaver kidneys were transplanted, 255 in the same town and 160 trabsported from a town another. A significative rise in cold ischemia times happened recently because of the increasing number of transported kidneys.", "contents": "[Organization and results of cadaver kidney transplantation from 1969 to 1973 (author's transl)]. France transplant was founded in order to organize rationally the cadaver kidneys transport and transplantation with is omogenous compatibility tests. 2143 hemodialysis patients have been presently (1-9-72) treated in 82 dialysis center in France; 964 of them are in the France Transplant waiting list. According with recent laws, nervous function cessation is synonimous of death. That made possible, by good resuscitation techniques, to maintain a good level of circulation and oxigenation of organs. Family permit is required for this purpose. 17 medical transporttion staffs are at work in 12 France towns and cooperate with 12 typing laboratoires working with the same techniques and reagents. One permanent secretariat in Paris is always telex connected with all staffs and mantains a continuous up to date patients waiting list. 415 cadaver kidneys were transplanted, 255 in the same town and 160 trabsported from a town another. A significative rise in cold ischemia times happened recently because of the increasing number of transported kidneys."}
{"id": "PMID:9124", "title": "Stimulation of the peripheral chemoreceptors with sodium bicarbonate.", "content": "The i.v. administration of sodium bicarbonate was found to cause an increase in arterial pH, followed by an increase in PaCO2. This caused a large increase in lung ventilation in in PaO2. Oxygen administration in human subjects, and anatomical denervation of the chemoreceptors in dogs, caused a substantial delay in the ventilatory responses to sodium bicarbonate. It was concluded that the i.v. administration of sodium bicarbonate provides a method of testing the presence of peripheral chemoreflexes which has the advantage of being independent of alveolar ventilation.", "contents": "Stimulation of the peripheral chemoreceptors with sodium bicarbonate. The i.v. administration of sodium bicarbonate was found to cause an increase in arterial pH, followed by an increase in PaCO2. This caused a large increase in lung ventilation in in PaO2. Oxygen administration in human subjects, and anatomical denervation of the chemoreceptors in dogs, caused a substantial delay in the ventilatory responses to sodium bicarbonate. It was concluded that the i.v. administration of sodium bicarbonate provides a method of testing the presence of peripheral chemoreflexes which has the advantage of being independent of alveolar ventilation."}
{"id": "PMID:9125", "title": "Oral premedication with oxypertine.", "content": "The preoperative effects of oral oxypertine have been compared with those of papaveretum and atropine in 185 patients in a double-blind between-patient study. Oxypertine 20 mg given orally as a nocturnal sedative and again on the morning of operation produced relief of anxiety comparable to that of papaveretum 10 mg and atropine 0.6 mg. It is concluded that oxypertine may be of value in medication before anaesthesia.", "contents": "Oral premedication with oxypertine. The preoperative effects of oral oxypertine have been compared with those of papaveretum and atropine in 185 patients in a double-blind between-patient study. Oxypertine 20 mg given orally as a nocturnal sedative and again on the morning of operation produced relief of anxiety comparable to that of papaveretum 10 mg and atropine 0.6 mg. It is concluded that oxypertine may be of value in medication before anaesthesia."}
{"id": "PMID:9127", "title": "Formation of anhydrosugars in the chemical depolymerization of heparin.", "content": "In the reactions used to break heparin down to mono- and oligosaccharides, androsugars are formed at two stages. The first of these is the well-known cleavage of heparin with nitrous acid to convert the N-sulfated D-glucosamines to anhydro-D-mannose residues; this reaction has been studied in detail. It is demonstrated here that only low pH (less than 2.5) reaction conditions favor the deamination of N-sulfated D-glucosamine residues; the reaction proceeds very slowly at pH 3.5 or above. On the other hand, N-unsubstituted amino sugars are deaminated at a maximum rate at pH 4 with markedly reduced rates at pH2 or pH6. At room temperature solutions of nitrous acid lose one-fourth to one-third of their capacity to deaminate amino sugars in 1 h at all pHs. A low pH nitrous acid reagent which will convert heparin quantitatively to its deamination products in 10 min at room temperature is described, and a comparison of the effectiveness of this reagent with other commonly used nitrous acid reagents is presented. It is also shown that conditions used for acid hydrolysis of heparin convert approximately one-fourth of the L-iduronosyluronic acid 2-sulfate residues to a 2,5-anhydrouronic acid. This product is an artifact of the reaction conditions, and its formation represents one of several pathways followed in the acid-catalyzed cleavage of the glycosidic bond of the sulfated L-idosyluronic acid residues.", "contents": "Formation of anhydrosugars in the chemical depolymerization of heparin. In the reactions used to break heparin down to mono- and oligosaccharides, androsugars are formed at two stages. The first of these is the well-known cleavage of heparin with nitrous acid to convert the N-sulfated D-glucosamines to anhydro-D-mannose residues; this reaction has been studied in detail. It is demonstrated here that only low pH (less than 2.5) reaction conditions favor the deamination of N-sulfated D-glucosamine residues; the reaction proceeds very slowly at pH 3.5 or above. On the other hand, N-unsubstituted amino sugars are deaminated at a maximum rate at pH 4 with markedly reduced rates at pH2 or pH6. At room temperature solutions of nitrous acid lose one-fourth to one-third of their capacity to deaminate amino sugars in 1 h at all pHs. A low pH nitrous acid reagent which will convert heparin quantitatively to its deamination products in 10 min at room temperature is described, and a comparison of the effectiveness of this reagent with other commonly used nitrous acid reagents is presented. It is also shown that conditions used for acid hydrolysis of heparin convert approximately one-fourth of the L-iduronosyluronic acid 2-sulfate residues to a 2,5-anhydrouronic acid. This product is an artifact of the reaction conditions, and its formation represents one of several pathways followed in the acid-catalyzed cleavage of the glycosidic bond of the sulfated L-idosyluronic acid residues."}
{"id": "PMID:9128", "title": "Influence of substrates and coenzymes on the role of manganous ion in reactions catalyzed by pig heart triphosphopyridine nucleotide-dependent isocitrate dehydrogenase.", "content": "The interaction of manganous ions with pig heart triphosphopyridine nucleotide (TPN) specific isocitrate dehydrogenase has been studied by kinetic experiments and by direct ultrafiltration measurements of manganous ion binding. At low metal ion concentrations, a lag is observed in the time-dependent production of reduced triphosphopyridine nucleotide (TPNH) that can be eliminated by adding 20 muM TPNH to the initial reaction mixture. A plot of 1/upsilon vs. 1/ (Mn2+) obtained at relatively high TPNH concentrations (20 muM) is linear and yields of Km value of 2 muM for metal ion, which is comparable to the direct binding constant measured in the presence of isocitrate. A similar plot at low TPNH concentrations (2 muM) reveals a biphasic relationship: at high metal concentrations the points are collinear with those obtained at high levels of TPNH, but at low metal concentrations that line is characterized by a Km of 19 muM for Mn2+. A difference in the deuterium oxide solvent isotope effect on Vmax observed with 20 muM TPNH as compared with 2 muM TPNH suggests that at high TPNH concentrations or high manganous ion concentrations the rate-limiting step is the dehydrogenation of isocitrate, while at low manganous ion concentrations and low TPNH concentrations, the slow step is the decarboxylation of enzyme-bound oxalosuccinate. Evidence to support this hypothesis is provided by the sensitivity to isocitrate concentration of the Km for total manganese measured in the presence of 20 muM TPNH that contrasts with the relative insensitivity to isocitrate of the Km measured at 2 muM TPNH and low manganous ion concentration. Direct measurements of oxalosuccinate decarboxylation reveal that the Vmax and the Km for manganous ion are influenced by the presence of oxidized or reduced TPN with the Km being lowest (5-7 muM) in the presence of TPNH. The dependence of the Km for manganous ion on the presence of substrate, TPN, and TPNH, is responsible for the variation with conditions in the rate-determining step. The enzyme binds only 1 mol of metal ion and 1 mol of isocitrate/mol of protein under all conditions. The pH dependence of the binding of free manganous ion, free isocitrate, and manganous-isocitrate complex indicates differences in the interaction of these species with isocitrate dehydrogenase. These results can be described in terms of two functions for manganous ion in the reactions catalyzed by isocitrate dehydrogenase, each of which requires a distinct binding site for metal ion: in the dehydrogenation step, Mn2+ facilitates the binding of the substrate isocitrate, and in the decarboxylation step it may stabilize the enolate of alpha-ketoglutarate which is generated.", "contents": "Influence of substrates and coenzymes on the role of manganous ion in reactions catalyzed by pig heart triphosphopyridine nucleotide-dependent isocitrate dehydrogenase. The interaction of manganous ions with pig heart triphosphopyridine nucleotide (TPN) specific isocitrate dehydrogenase has been studied by kinetic experiments and by direct ultrafiltration measurements of manganous ion binding. At low metal ion concentrations, a lag is observed in the time-dependent production of reduced triphosphopyridine nucleotide (TPNH) that can be eliminated by adding 20 muM TPNH to the initial reaction mixture. A plot of 1/upsilon vs. 1/ (Mn2+) obtained at relatively high TPNH concentrations (20 muM) is linear and yields of Km value of 2 muM for metal ion, which is comparable to the direct binding constant measured in the presence of isocitrate. A similar plot at low TPNH concentrations (2 muM) reveals a biphasic relationship: at high metal concentrations the points are collinear with those obtained at high levels of TPNH, but at low metal concentrations that line is characterized by a Km of 19 muM for Mn2+. A difference in the deuterium oxide solvent isotope effect on Vmax observed with 20 muM TPNH as compared with 2 muM TPNH suggests that at high TPNH concentrations or high manganous ion concentrations the rate-limiting step is the dehydrogenation of isocitrate, while at low manganous ion concentrations and low TPNH concentrations, the slow step is the decarboxylation of enzyme-bound oxalosuccinate. Evidence to support this hypothesis is provided by the sensitivity to isocitrate concentration of the Km for total manganese measured in the presence of 20 muM TPNH that contrasts with the relative insensitivity to isocitrate of the Km measured at 2 muM TPNH and low manganous ion concentration. Direct measurements of oxalosuccinate decarboxylation reveal that the Vmax and the Km for manganous ion are influenced by the presence of oxidized or reduced TPN with the Km being lowest (5-7 muM) in the presence of TPNH. The dependence of the Km for manganous ion on the presence of substrate, TPN, and TPNH, is responsible for the variation with conditions in the rate-determining step. The enzyme binds only 1 mol of metal ion and 1 mol of isocitrate/mol of protein under all conditions. The pH dependence of the binding of free manganous ion, free isocitrate, and manganous-isocitrate complex indicates differences in the interaction of these species with isocitrate dehydrogenase. These results can be described in terms of two functions for manganous ion in the reactions catalyzed by isocitrate dehydrogenase, each of which requires a distinct binding site for metal ion: in the dehydrogenation step, Mn2+ facilitates the binding of the substrate isocitrate, and in the decarboxylation step it may stabilize the enolate of alpha-ketoglutarate which is generated."}
{"id": "PMID:9129", "title": "Interaction of 1,N6-ethenoadenine derivatives of triphosphopyridine and reduced triphosphopyridine nucleotides with dihydrofolate reductase from amethopterin-resistant L1210 cells.", "content": "The 1,N6-ethenoadenine derivatives of triphosphopyridine and reduced triphosphopyridine nucleotides (TPN and TPNH) epsilon-TPN and epsilon-TPNH) have been synthesized and used as fluorescent probes to examine the pyridine nucleotide binding site of L1210 dihydrofolate reductase. Epsilon-TPNH (Km = 16.7 muM) was able to replace TPNH (Km = 3.8 muM) in the enzyme-catalyzed reduction of dihyrdofolate, and both epsilon-TPN and epsilon-TPNH formed binary complexes with the enzyme that were stable to polyacrylamide gel electrophoresis. The fluorescence of epsilon-TPN was enhanced and the emission maximum shifted from 415 to 405 nm when the nucleotide was bound to the enzyme. The ethenoadenine moiety in epsilon-TPNH behaved similarily, but the fluorescence changes were complicated by concurrent effects of binding upon the dihydronicotinamide fluorophore. Fluorescence enhancement titrations yielded values of 1.8 and 0.59 muM, respectively, for the dissociation constants of the enzyme-epsilon-TPN and enzyme-epsilon-TPNH complexes. Titration experiments based upon quenching of enzyme fluorescence gave similar values, viz., 2.1 and 0.53 muM for the dissociation constants of these complexes. Fluorimetric titration of the enzyme-TPNH complex with epsilon-TPN (or of the enzyme-TPN complex with epsilon-TPNH) failed to reveal the presence of a second pyridine nucleotide binding site. The fluorescence enhancement of enzyme-bound epsilon-TPN or dihydrofolate was quenched when amethopterin or epsilon-TPN, respectively, was added to form a ternary complex. These results provide information concerning the nature of the pyridine nucleotide binding site and its spatial relationship to the dihydrofolate/amethopterin binding site.", "contents": "Interaction of 1,N6-ethenoadenine derivatives of triphosphopyridine and reduced triphosphopyridine nucleotides with dihydrofolate reductase from amethopterin-resistant L1210 cells. The 1,N6-ethenoadenine derivatives of triphosphopyridine and reduced triphosphopyridine nucleotides (TPN and TPNH) epsilon-TPN and epsilon-TPNH) have been synthesized and used as fluorescent probes to examine the pyridine nucleotide binding site of L1210 dihydrofolate reductase. Epsilon-TPNH (Km = 16.7 muM) was able to replace TPNH (Km = 3.8 muM) in the enzyme-catalyzed reduction of dihyrdofolate, and both epsilon-TPN and epsilon-TPNH formed binary complexes with the enzyme that were stable to polyacrylamide gel electrophoresis. The fluorescence of epsilon-TPN was enhanced and the emission maximum shifted from 415 to 405 nm when the nucleotide was bound to the enzyme. The ethenoadenine moiety in epsilon-TPNH behaved similarily, but the fluorescence changes were complicated by concurrent effects of binding upon the dihydronicotinamide fluorophore. Fluorescence enhancement titrations yielded values of 1.8 and 0.59 muM, respectively, for the dissociation constants of the enzyme-epsilon-TPN and enzyme-epsilon-TPNH complexes. Titration experiments based upon quenching of enzyme fluorescence gave similar values, viz., 2.1 and 0.53 muM for the dissociation constants of these complexes. Fluorimetric titration of the enzyme-TPNH complex with epsilon-TPN (or of the enzyme-TPN complex with epsilon-TPNH) failed to reveal the presence of a second pyridine nucleotide binding site. The fluorescence enhancement of enzyme-bound epsilon-TPN or dihydrofolate was quenched when amethopterin or epsilon-TPN, respectively, was added to form a ternary complex. These results provide information concerning the nature of the pyridine nucleotide binding site and its spatial relationship to the dihydrofolate/amethopterin binding site."}
{"id": "PMID:9130", "title": "Thyroid Ribonucleic Acid-Iodopeptides. Comparison of Tyrosyl-Complex II and Tyrosyl-tRNA.", "content": "It has previously been shown that mammalian RNA-peptidyl complexes are found in close association with tRNA, but can be separated from the bulk of the tRNA by benzoylated diethylaminoethylcellulose chromatography (Kull, F.J., and Soodak, M. (1971), Biochim. Biophys. Acta 246, l; Gadski, R.A., and Kull, F.J. (1973), Biochemistry 12, 1907). These studies also showed that under aminoacylation conditions the complex fractions were able to act as acceptors for certain amino acids and that the formation of porcine thyroid tyrosyl-complex II was particularly high. Because of this high acceptor function, and because of the importance of tyrosine to thyroid metabolism, further studies were conducted comparing some of the properties of porcine thyroid tyrosyl-complex II with those of porcine thyroid tyrosyl-tRNA. Porcine thyroid tyrosyl-tRNA synthetase was purified in excess of 200-fold and characterized. It was found that maximal aminoacylation was achieved at pH 8.1 in the presence of 150 mM KCl. The Km for tyrosine was determined to be 3.0 X 10(-6) M. The purified thyroid tyrosyl-tRNA synthetase was used under aminoacylation conditions to prepare radioactively labeled porcine thyroid tyrosyl-tRNA and tyrosyl-complex II. Comparisons made using reversed-phase column chromatography (RPC-5) showed distinct differences between the two aminoacylated species and revealed, in addition, a number of isoaccepting forms of tyrosine tRNA. Tyrosyl-complex II was also found to differ from tyrosyl-tRNA in that it is more stable to deacylation at pH 7.0 and at pH 4.4 and to degradation by ribonuclease A. In addition, tyrosyl-complex II, unlike tyrosyl-tRNA, is degraded by trypsin. Ribosomal binding studies showed that tyrosyl-complex II did not respond to the codons for tyrosine, UpApU and UpApC, whereas tyrosyl-tRNA responded to both. It is suggested that thyroid tyrosine complex II is representative of a group of related complexes that constitute the complex II fraction and that, although the complexes resemble tRNA in many respects, they have distinctly different characteristics than conventional tRNA.", "contents": "Thyroid Ribonucleic Acid-Iodopeptides. Comparison of Tyrosyl-Complex II and Tyrosyl-tRNA. It has previously been shown that mammalian RNA-peptidyl complexes are found in close association with tRNA, but can be separated from the bulk of the tRNA by benzoylated diethylaminoethylcellulose chromatography (Kull, F.J., and Soodak, M. (1971), Biochim. Biophys. Acta 246, l; Gadski, R.A., and Kull, F.J. (1973), Biochemistry 12, 1907). These studies also showed that under aminoacylation conditions the complex fractions were able to act as acceptors for certain amino acids and that the formation of porcine thyroid tyrosyl-complex II was particularly high. Because of this high acceptor function, and because of the importance of tyrosine to thyroid metabolism, further studies were conducted comparing some of the properties of porcine thyroid tyrosyl-complex II with those of porcine thyroid tyrosyl-tRNA. Porcine thyroid tyrosyl-tRNA synthetase was purified in excess of 200-fold and characterized. It was found that maximal aminoacylation was achieved at pH 8.1 in the presence of 150 mM KCl. The Km for tyrosine was determined to be 3.0 X 10(-6) M. The purified thyroid tyrosyl-tRNA synthetase was used under aminoacylation conditions to prepare radioactively labeled porcine thyroid tyrosyl-tRNA and tyrosyl-complex II. Comparisons made using reversed-phase column chromatography (RPC-5) showed distinct differences between the two aminoacylated species and revealed, in addition, a number of isoaccepting forms of tyrosine tRNA. Tyrosyl-complex II was also found to differ from tyrosyl-tRNA in that it is more stable to deacylation at pH 7.0 and at pH 4.4 and to degradation by ribonuclease A. In addition, tyrosyl-complex II, unlike tyrosyl-tRNA, is degraded by trypsin. Ribosomal binding studies showed that tyrosyl-complex II did not respond to the codons for tyrosine, UpApU and UpApC, whereas tyrosyl-tRNA responded to both. It is suggested that thyroid tyrosine complex II is representative of a group of related complexes that constitute the complex II fraction and that, although the complexes resemble tRNA in many respects, they have distinctly different characteristics than conventional tRNA."}
{"id": "PMID:9131", "title": "Molecular polymorphism and mechanisms of activation and deactivation of the hydrolytic function of the coupling factor of oxidative phosphorylation.", "content": "The 13S coupling factor of oxidative phosphorylation from Alcaligenes faecalis has a latent adenosine triphosphatase (ATPase) function that can be activated by heating at 55 degrees C for 10 min at pH 8.5 in 50% glycerol. The specific activity increases from 0.1 to 20--30 mumol min-1 mg-1. Adenosine 5'-triphosphate (ATP) is not required for stabilization at 55 degreesC when glycerol is present. Activation involves displacement of the endogenous ATPase inhibitor subunit (epsilon subunit), and readdition of this subunit results in deactivation. In the deactivation process the ATPase inhibitor subunit can be replaced by other cationic proteins such as protamine, histones, or poly(lysine). Mg2+ and H+ also are effective deactivators. The fact that every positively charged substance tested deactivated the enzyme suggests that the inhibitor subunit is complexed with the enzyme at a site containing a surplus of negative charges. The activated enzyme is not labile, but it is salt labile, having a half-life of 2-3 min in 0.1 M KI at either 25 or 0 degrees C. The activated ATPase is also inhibited by aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD), and by the cross-linking agent dimethyl suberimidate. Evidence for polymorphism comes from finding that the properties of the unactivated enzyme (intrinsic ATPase) are different in many ways from the properties of activated ATPase. With respect to the coupling factor's ability to hydrolyze ATP, the data in this study suggest that there are at least four distinct functional allomorphs of this enzyme: (1) the latent enzyme, which has no kinetically measurable ATPase activity, (2) intrinsic ATPase, which is catalyzed by a small percentage of the molecular population that has been activated by some natural mechanism, (3) activated ATPase, which has properties different from those of intrinsic ATPase, and (4) aged activated ATPase, in which some of the properties (Km for substrate, sensitivity to deactivation by Mg2+ and H+) spontaneously change within 30 min.", "contents": "Molecular polymorphism and mechanisms of activation and deactivation of the hydrolytic function of the coupling factor of oxidative phosphorylation. The 13S coupling factor of oxidative phosphorylation from Alcaligenes faecalis has a latent adenosine triphosphatase (ATPase) function that can be activated by heating at 55 degrees C for 10 min at pH 8.5 in 50% glycerol. The specific activity increases from 0.1 to 20--30 mumol min-1 mg-1. Adenosine 5'-triphosphate (ATP) is not required for stabilization at 55 degreesC when glycerol is present. Activation involves displacement of the endogenous ATPase inhibitor subunit (epsilon subunit), and readdition of this subunit results in deactivation. In the deactivation process the ATPase inhibitor subunit can be replaced by other cationic proteins such as protamine, histones, or poly(lysine). Mg2+ and H+ also are effective deactivators. The fact that every positively charged substance tested deactivated the enzyme suggests that the inhibitor subunit is complexed with the enzyme at a site containing a surplus of negative charges. The activated enzyme is not labile, but it is salt labile, having a half-life of 2-3 min in 0.1 M KI at either 25 or 0 degrees C. The activated ATPase is also inhibited by aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD), and by the cross-linking agent dimethyl suberimidate. Evidence for polymorphism comes from finding that the properties of the unactivated enzyme (intrinsic ATPase) are different in many ways from the properties of activated ATPase. With respect to the coupling factor's ability to hydrolyze ATP, the data in this study suggest that there are at least four distinct functional allomorphs of this enzyme: (1) the latent enzyme, which has no kinetically measurable ATPase activity, (2) intrinsic ATPase, which is catalyzed by a small percentage of the molecular population that has been activated by some natural mechanism, (3) activated ATPase, which has properties different from those of intrinsic ATPase, and (4) aged activated ATPase, in which some of the properties (Km for substrate, sensitivity to deactivation by Mg2+ and H+) spontaneously change within 30 min."}
{"id": "PMID:9132", "title": "Histidine decarboxylase of Lactobacillus 30a: function and reactivity of sulfhydryl groups.", "content": "Two classes of sulfhydryl groups in histidine decarboxylase from Lactobacillus 30 a can be differentiated by their reaction with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Five cysteinyl residues (class I) of the native enzyme are titrated by DTNB as the pH of the reaction medium is increased from 6.5 to 7.5; the pH-rate profile for their reaction is described by a pKa of 9.2. An additional five thiol groups (class II) are titrated only when denaturing agents are added above neutral pH. Histidine decarboxylase is completely inactivated by DTNB in a kinetically second-order process (Kapp = 660 +/- 20 M-1 min-1 at pH 7.6 and 25 degrees C) which occurs coincident with and at the same rate as modification of the five class-I SH groups of the enzyme, i.e., one thiol group per pyruvoyl prosthetic group. The competitive inhibitors, histamine and imidazole, markedly enhanced the reactivity of these cysteinyl residues toward DTNB; this enhancement is accompanied by a concomitant increase in the rate of inactivation. A single SH group in each of the five catalytic units of histidine decarboxylase is thus implicated as being critical for the expression of enzymatic activity.", "contents": "Histidine decarboxylase of Lactobacillus 30a: function and reactivity of sulfhydryl groups. Two classes of sulfhydryl groups in histidine decarboxylase from Lactobacillus 30 a can be differentiated by their reaction with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Five cysteinyl residues (class I) of the native enzyme are titrated by DTNB as the pH of the reaction medium is increased from 6.5 to 7.5; the pH-rate profile for their reaction is described by a pKa of 9.2. An additional five thiol groups (class II) are titrated only when denaturing agents are added above neutral pH. Histidine decarboxylase is completely inactivated by DTNB in a kinetically second-order process (Kapp = 660 +/- 20 M-1 min-1 at pH 7.6 and 25 degrees C) which occurs coincident with and at the same rate as modification of the five class-I SH groups of the enzyme, i.e., one thiol group per pyruvoyl prosthetic group. The competitive inhibitors, histamine and imidazole, markedly enhanced the reactivity of these cysteinyl residues toward DTNB; this enhancement is accompanied by a concomitant increase in the rate of inactivation. A single SH group in each of the five catalytic units of histidine decarboxylase is thus implicated as being critical for the expression of enzymatic activity."}
{"id": "PMID:9133", "title": "Kinetic analysis of the individual reductive steps catalyzed by beta-hydroxy-beta-methylglutaryl-coenzyme A reductase obtained from yeast.", "content": "The mechanism of action of yeast beta-hydroxy-beta-methylglutaryl-coenzyme A reductase has been investigated through kinetic studies on the oxidation of mevaldate by nicotinamide adeninine dinucleotide phosphate (NADP) in the presence of coenzyme A (CoA) and on the reduction of mevaldate by reduced NADP (NADPH) in the absence of presence of CoA or acetyl-CoA. NADP and mevalonate were also used as product inhibitors of the reduction of mevaldate. In the reduction of mevaldate to mevalonate, coenzyme A and acetyl-CoA decreased the Km for mevaldate 30- and 3-fold, respectively. Both compounds increased the Vmax 1.5-fold. These results suggest that CoA is an allosteric activator for the second reductive step and that it acts by enhancing the binding of mevaldate. The intersecting patterns obtained from initial velocities and the patterns produced by product inhibitions suggest the following features of the mechanism. The binding of substrates and release of products proceeds sequentially in both reductive steps, and is ordered throughout or random with respect to the binding of the beta-hydroxy-beta-methylglutaryl-coenzymeA and the first NADPH. The binding of NADPH enhances the binding of the beta-hydroxy-beta-methylglutaryl portion of the CoA ester and the binding of free mevaldate, whereas the binding of NADP leads to an increased affinity of the enzyme for the hemithioacetal (of mevaldate and CoA) and for mevalonate. Thus, the replacement of NADP by NADPH after the first reductive step promotes the conversion of the hemithioacetal to the free carbonyl form, which is then rapidly reduced. The products, CoA and mevalonic acid, of the second reductive step leave the enzyme before the release of the second NADP. This release of the last product is probably the rate-limiting step for the overall process.", "contents": "Kinetic analysis of the individual reductive steps catalyzed by beta-hydroxy-beta-methylglutaryl-coenzyme A reductase obtained from yeast. The mechanism of action of yeast beta-hydroxy-beta-methylglutaryl-coenzyme A reductase has been investigated through kinetic studies on the oxidation of mevaldate by nicotinamide adeninine dinucleotide phosphate (NADP) in the presence of coenzyme A (CoA) and on the reduction of mevaldate by reduced NADP (NADPH) in the absence of presence of CoA or acetyl-CoA. NADP and mevalonate were also used as product inhibitors of the reduction of mevaldate. In the reduction of mevaldate to mevalonate, coenzyme A and acetyl-CoA decreased the Km for mevaldate 30- and 3-fold, respectively. Both compounds increased the Vmax 1.5-fold. These results suggest that CoA is an allosteric activator for the second reductive step and that it acts by enhancing the binding of mevaldate. The intersecting patterns obtained from initial velocities and the patterns produced by product inhibitions suggest the following features of the mechanism. The binding of substrates and release of products proceeds sequentially in both reductive steps, and is ordered throughout or random with respect to the binding of the beta-hydroxy-beta-methylglutaryl-coenzymeA and the first NADPH. The binding of NADPH enhances the binding of the beta-hydroxy-beta-methylglutaryl portion of the CoA ester and the binding of free mevaldate, whereas the binding of NADP leads to an increased affinity of the enzyme for the hemithioacetal (of mevaldate and CoA) and for mevalonate. Thus, the replacement of NADP by NADPH after the first reductive step promotes the conversion of the hemithioacetal to the free carbonyl form, which is then rapidly reduced. The products, CoA and mevalonic acid, of the second reductive step leave the enzyme before the release of the second NADP. This release of the last product is probably the rate-limiting step for the overall process."}
{"id": "PMID:9134", "title": "Conformational changes in subfractions of calf thymus histone H1.", "content": "This paper presents the first study of conformational changes in the subfractions of calf thymus H1. H1 was fractionated by the method of Kincade and Cole (Kincade, J. M., and Cole, R.D. (1966), J. Biol. Chem. 241. 5790) using a very shallow Gdn-HC1 gradient. A possible new H1 subfraction, about 5--8% of the H1, has been found and characterized by amino acid analysis and electrophoresis. The effects of salt concentration and pH on the conformation of each of the four major subfractions have been studied by measuring the fluorescence anisotropy of the tyrosine emission and the circular dichroism (CD) of the peptide bond. Upon the addition of salt to aqueous solutions at neutral pH, all four subfractions show an instantaneous change in fluorescence anisotropy, fluorescence intensity, tyrosine absorbance, and CD. The folding associated with this instantaneous change is highly cooperative, and involves the region of the molecule containing the lone tyrosine, which becomes buried in the folded form. The folding of subfraction 3a is more sensitive to salt than the other major subfractions. Upon folding, approximately 13% of the residues of subfractions 1b and 2 form alpha and beta structure; 3a and 3b have approximately 16% of the residues in alpha and beta structures. There is no evidence for interactions between the subfractions. In salt-free solutions, each of the four major subfractions show very little change in conformation in going from low to neutral pH, but each shows a very sharp transition near pH 9. This transition gives rise to a marked increase in fluorescence anisotropy and fluorescence intensity, and involves the formation of both alpha and beta strucute in a manner similar to that of the salt-induced state.", "contents": "Conformational changes in subfractions of calf thymus histone H1. This paper presents the first study of conformational changes in the subfractions of calf thymus H1. H1 was fractionated by the method of Kincade and Cole (Kincade, J. M., and Cole, R.D. (1966), J. Biol. Chem. 241. 5790) using a very shallow Gdn-HC1 gradient. A possible new H1 subfraction, about 5--8% of the H1, has been found and characterized by amino acid analysis and electrophoresis. The effects of salt concentration and pH on the conformation of each of the four major subfractions have been studied by measuring the fluorescence anisotropy of the tyrosine emission and the circular dichroism (CD) of the peptide bond. Upon the addition of salt to aqueous solutions at neutral pH, all four subfractions show an instantaneous change in fluorescence anisotropy, fluorescence intensity, tyrosine absorbance, and CD. The folding associated with this instantaneous change is highly cooperative, and involves the region of the molecule containing the lone tyrosine, which becomes buried in the folded form. The folding of subfraction 3a is more sensitive to salt than the other major subfractions. Upon folding, approximately 13% of the residues of subfractions 1b and 2 form alpha and beta structure; 3a and 3b have approximately 16% of the residues in alpha and beta structures. There is no evidence for interactions between the subfractions. In salt-free solutions, each of the four major subfractions show very little change in conformation in going from low to neutral pH, but each shows a very sharp transition near pH 9. This transition gives rise to a marked increase in fluorescence anisotropy and fluorescence intensity, and involves the formation of both alpha and beta strucute in a manner similar to that of the salt-induced state."}
{"id": "PMID:9135", "title": "Conformation of the extracellular polysaccharide of Xanthomonas campestris.", "content": "The solution conformation of the extracellular polysaccharide of the bacterium Xanthomonas campestris is examined by optical rotation, viscometry, and potentiometric titration. Measurements of optical rotation vs. temperature for solutions of the polysaccharide at low ionic strength reveal a sharp transition to a denatured structure which is reversible if sufficient salt is present. The temperature Tm at the transition midpoint increases as log (Na+) or log (Ca2+). Viscosity-temperature profiles substantiate a structural change of the polysaccharide at Tm. The intrinsic viscosity of the native molecule at zero shear rate exceeds 5000 ml/g. This high figure is indicative of a stiff chain. The viscosity of the native molecule is relatively insensitive to salt, whereas the denatured molecule collapses if salt is present. Hydrogen-ion titration shows that the pKapp of the COO- groups of the polymer decreases from 3.2 in 0.01 M NaC1 to 2.6 in 0.2 M NaC1. All these data suggest that the native polysaccharide possesses ordered secondary structure stabilized by nonionic interactions outweighing the repulsion between adjacent COO- groups.", "contents": "Conformation of the extracellular polysaccharide of Xanthomonas campestris. The solution conformation of the extracellular polysaccharide of the bacterium Xanthomonas campestris is examined by optical rotation, viscometry, and potentiometric titration. Measurements of optical rotation vs. temperature for solutions of the polysaccharide at low ionic strength reveal a sharp transition to a denatured structure which is reversible if sufficient salt is present. The temperature Tm at the transition midpoint increases as log (Na+) or log (Ca2+). Viscosity-temperature profiles substantiate a structural change of the polysaccharide at Tm. The intrinsic viscosity of the native molecule at zero shear rate exceeds 5000 ml/g. This high figure is indicative of a stiff chain. The viscosity of the native molecule is relatively insensitive to salt, whereas the denatured molecule collapses if salt is present. Hydrogen-ion titration shows that the pKapp of the COO- groups of the polymer decreases from 3.2 in 0.01 M NaC1 to 2.6 in 0.2 M NaC1. All these data suggest that the native polysaccharide possesses ordered secondary structure stabilized by nonionic interactions outweighing the repulsion between adjacent COO- groups."}
{"id": "PMID:9136", "title": "The reduction kinetics of chlorophyll aI as an indicator for proton uptake between the light reactions in chloroplasts.", "content": "The flash-induced oxidation kinetics of the primary acceptor of light Reaction II (X-320) and the reduction kinetics of chlorophyll aI (P-700) after far-red preillumination have been studied with high time resolution in spinach chloroplasts. 1. The kinetics of chlorophyll aI exhibits a pronounced lag phase of 2--3 ms at the onset of reduction as would be expected for the final product of consecutive reactions. Because the oxidation of the plastoquinone pool is the rate-limiting step for the electron transport between the two light reactions, the lag indicates the maximal electron transfer time over all preceding reactions after light Reaction II. 2. The observation that the lag phase decreases with decreasing pH is evidence of an electron transfer step coupled to a proton uptake reaction. 3. Protonation of X-320 after reduction in the flash is excluded because a slight increase of the decay time is found at decreasing pH values. 4. The time course of plastohydroquinone formation is deduced from the first derivative of the reduction kinetics of chlorophyll aI. This approach covers those plastohydroquinone molecules being available to the electron carriers of System I via the rate-limiting step. Direct measurements of absorbance changes would not allow to discriminate between these and functionally different plastohydroquinone molecules. 5. The derived time course of plastohydroquinone at different pH gives evidence for an additional electron transfer step with a half time of about 1 ms following the proton uptake and preceding the rate-limiting step. It is tentatively attributed to the diffusion of neutral plastohydroquinone across the hydrophobic core of the thylkaloid membrane. 6. The lower limit of the rate constant for proton uptake by an electron carrier, consistent with the lag of chlorophyll aI reduction, is estimated as greater than 10(11) M-1s-1. The value is higher than that of the fastest diffusion controlled protonations of organic molecules in solution. Possible mechanisms of linear electron transport between light Reaction II and the rate-limiting oxidation of neutral plastohydroquinone are thoroughly discussed.", "contents": "The reduction kinetics of chlorophyll aI as an indicator for proton uptake between the light reactions in chloroplasts. The flash-induced oxidation kinetics of the primary acceptor of light Reaction II (X-320) and the reduction kinetics of chlorophyll aI (P-700) after far-red preillumination have been studied with high time resolution in spinach chloroplasts. 1. The kinetics of chlorophyll aI exhibits a pronounced lag phase of 2--3 ms at the onset of reduction as would be expected for the final product of consecutive reactions. Because the oxidation of the plastoquinone pool is the rate-limiting step for the electron transport between the two light reactions, the lag indicates the maximal electron transfer time over all preceding reactions after light Reaction II. 2. The observation that the lag phase decreases with decreasing pH is evidence of an electron transfer step coupled to a proton uptake reaction. 3. Protonation of X-320 after reduction in the flash is excluded because a slight increase of the decay time is found at decreasing pH values. 4. The time course of plastohydroquinone formation is deduced from the first derivative of the reduction kinetics of chlorophyll aI. This approach covers those plastohydroquinone molecules being available to the electron carriers of System I via the rate-limiting step. Direct measurements of absorbance changes would not allow to discriminate between these and functionally different plastohydroquinone molecules. 5. The derived time course of plastohydroquinone at different pH gives evidence for an additional electron transfer step with a half time of about 1 ms following the proton uptake and preceding the rate-limiting step. It is tentatively attributed to the diffusion of neutral plastohydroquinone across the hydrophobic core of the thylkaloid membrane. 6. The lower limit of the rate constant for proton uptake by an electron carrier, consistent with the lag of chlorophyll aI reduction, is estimated as greater than 10(11) M-1s-1. The value is higher than that of the fastest diffusion controlled protonations of organic molecules in solution. Possible mechanisms of linear electron transport between light Reaction II and the rate-limiting oxidation of neutral plastohydroquinone are thoroughly discussed."}
{"id": "PMID:9137", "title": "An estimation of the light-induced electrochemical potential difference of protons across the membrane of Halobacterium halobium.", "content": "The light-dependent uptake of triphenylmethylphosphonium (TPMP+) and of 5,5-dimethyloxazolidine-2,4-dione (DMO) by starved purple cells of Halobacterium halobium was investigated. DMO uptake was used to calculate the pH difference (deltapH) across the membrane, and TPMP+ was used as an index of the electrical potential difference, deltapsi. Under most conditions, both in the light and in the dark, the cells are more alkaline than the medium. In the light at pH 6.6, deltapH amounts to 0.6-0.8 pH unit. Its value can be increased to 1.5-2.0 by either incubating the cells with TPMP+ (10(-3) M) or at low external pH (5.5). --deltapH can be lowered by uncoupler or by nigericin. The TPMP+ uptake by the cells indicates a large deltapsi across the membrane, negative inside. It was estimated that in the light, at pH 6.6, deltapsi might reach a value of about 100 mV and that consequently the electrical equivalent of the proton electrochemical potential difference, deltamuH+/F, amounts under these conditions to about 140 mV. The effects of different ionophores on the light-drive proton extrusion by the cells were in agreement with the effects of these compounds on --deltapH.", "contents": "An estimation of the light-induced electrochemical potential difference of protons across the membrane of Halobacterium halobium. The light-dependent uptake of triphenylmethylphosphonium (TPMP+) and of 5,5-dimethyloxazolidine-2,4-dione (DMO) by starved purple cells of Halobacterium halobium was investigated. DMO uptake was used to calculate the pH difference (deltapH) across the membrane, and TPMP+ was used as an index of the electrical potential difference, deltapsi. Under most conditions, both in the light and in the dark, the cells are more alkaline than the medium. In the light at pH 6.6, deltapH amounts to 0.6-0.8 pH unit. Its value can be increased to 1.5-2.0 by either incubating the cells with TPMP+ (10(-3) M) or at low external pH (5.5). --deltapH can be lowered by uncoupler or by nigericin. The TPMP+ uptake by the cells indicates a large deltapsi across the membrane, negative inside. It was estimated that in the light, at pH 6.6, deltapsi might reach a value of about 100 mV and that consequently the electrical equivalent of the proton electrochemical potential difference, deltamuH+/F, amounts under these conditions to about 140 mV. The effects of different ionophores on the light-drive proton extrusion by the cells were in agreement with the effects of these compounds on --deltapH."}
{"id": "PMID:9138", "title": "Reactions of the ferri-ferrocytochrome-c system with superoxide/oxygen and CO2-/CO2 studied by fast pulse radiolysis.", "content": "The reduction of ferricytochrome c by O2- and CO2- was studied in the pH range 6.6-9.2 and Arrhenius as well as Eyring parameters were derived from the rate constants and their temperature dependence. Ionic effects on the rate indicate that the redox process proceeds through a multiply-positively charged interaction site on cytochrome c. It is shown that the reaction with O2- (and correspondingly with O2 of ferrocytochrome c) is by a factor of approx. 10(3) slower than warranted by factors such as redox potential. Evidence is adduced to support the view that this slowness is connected with the role of water in the interaction between O2-/O2 and ferri-ferrocytochrome c in the positively charged interaction site on cytochrome c in which water molecules are specifically involved in maintaining the local structure of cytochrome c and participate in the process of electron equivalent transfer.", "contents": "Reactions of the ferri-ferrocytochrome-c system with superoxide/oxygen and CO2-/CO2 studied by fast pulse radiolysis. The reduction of ferricytochrome c by O2- and CO2- was studied in the pH range 6.6-9.2 and Arrhenius as well as Eyring parameters were derived from the rate constants and their temperature dependence. Ionic effects on the rate indicate that the redox process proceeds through a multiply-positively charged interaction site on cytochrome c. It is shown that the reaction with O2- (and correspondingly with O2 of ferrocytochrome c) is by a factor of approx. 10(3) slower than warranted by factors such as redox potential. Evidence is adduced to support the view that this slowness is connected with the role of water in the interaction between O2-/O2 and ferri-ferrocytochrome c in the positively charged interaction site on cytochrome c in which water molecules are specifically involved in maintaining the local structure of cytochrome c and participate in the process of electron equivalent transfer."}
{"id": "PMID:9139", "title": "Binding of ampholine to transfer RNA.", "content": "The melting temperature of isoaccepting tRNAfMet is affected by Ampholine. The plot of Tm versus the logarithm of Ampholine concentration shows clearly an increasing effect of Ampholine when the pH changes from 7.4 to 4.2. This result is interpreted as binding of Ampholine to the nucleic acid. The effects of Ampholine have been compared with those of soidum, magnesium and tetraethylene pentamine. Ampholine carrier ampholytes at pH 4.2 bind to tRNA with the same affinity as magnesium; at higher pH values they are less active. An hypothesis for the mechanism of action of Ampholine on nucleic acids during isoelectric focusing is proposed.", "contents": "Binding of ampholine to transfer RNA. The melting temperature of isoaccepting tRNAfMet is affected by Ampholine. The plot of Tm versus the logarithm of Ampholine concentration shows clearly an increasing effect of Ampholine when the pH changes from 7.4 to 4.2. This result is interpreted as binding of Ampholine to the nucleic acid. The effects of Ampholine have been compared with those of soidum, magnesium and tetraethylene pentamine. Ampholine carrier ampholytes at pH 4.2 bind to tRNA with the same affinity as magnesium; at higher pH values they are less active. An hypothesis for the mechanism of action of Ampholine on nucleic acids during isoelectric focusing is proposed."}
{"id": "PMID:9140", "title": "Purification and properties of alkaline ribonuclease from human serum.", "content": "1. Five alkaline ribonucleases (EC 3.1.4.22) were purified about 140- to 1900-fold from human serum by phosphocellulose and DEAE-cellulose chromatographies and Sephadex G-75 filtration, with a total recovery of 22%. These were designated as RNAases 1-5. 2. Optimum activities were observed at pH 8.5-8.7 for RNAases 1-4, and at pH 7.5 for RNAase 5. The molecular weights of these enzymes were estimated by gel filtration as 45 000, 32 000, 20 000, 13 000 and 8500, respectively. 3. These RNAases were found to be heat-labile proteins but are markedly stabilized with bovine plasma albumin. The reaction was activated by Na+, K+, Mg2+ and Ca2+, and inhibited by Co2+, Fe2+, Cu2+ and Zn2+. EDTA had little effect on the velocity of the reaction. Spermine caused 2- to 7-fold activation. 4. Among the substrates examined, these RNAases preferentially hydrolyzed pyrimidine bodies and except for RNAase 5 had a higher affinity for poly(C) than poly(U) as substrate. Each enzyme was free from other nucleolytic enzymes and hydrolyzed only RNA.", "contents": "Purification and properties of alkaline ribonuclease from human serum. 1. Five alkaline ribonucleases (EC 3.1.4.22) were purified about 140- to 1900-fold from human serum by phosphocellulose and DEAE-cellulose chromatographies and Sephadex G-75 filtration, with a total recovery of 22%. These were designated as RNAases 1-5. 2. Optimum activities were observed at pH 8.5-8.7 for RNAases 1-4, and at pH 7.5 for RNAase 5. The molecular weights of these enzymes were estimated by gel filtration as 45 000, 32 000, 20 000, 13 000 and 8500, respectively. 3. These RNAases were found to be heat-labile proteins but are markedly stabilized with bovine plasma albumin. The reaction was activated by Na+, K+, Mg2+ and Ca2+, and inhibited by Co2+, Fe2+, Cu2+ and Zn2+. EDTA had little effect on the velocity of the reaction. Spermine caused 2- to 7-fold activation. 4. Among the substrates examined, these RNAases preferentially hydrolyzed pyrimidine bodies and except for RNAase 5 had a higher affinity for poly(C) than poly(U) as substrate. Each enzyme was free from other nucleolytic enzymes and hydrolyzed only RNA."}
{"id": "PMID:9141", "title": "Sites of alkylation of poly(U) by agents of varying carcinogenicity and stability of products.", "content": "Several alkylating agents of widely varying reported carcinogenicity (dimethylsulfate, diethylsulfate, ethylmethanesulfonate, methylnitrosourea, ethylnitrosourea and ethylnitrosoguanidine) were reacted with poly(U) at pH values ranging from 4.5 to 7.5. All nucleophilic centers (internal phosphate groups, ribose hydroxyls, and O2, N-3 and O4 sites of the uracil base) were found reactive, though to different extents, at neutrality and in slightly acid solution. The distribution of products is a function of the alkylating agent and pH. The nitroso compounds are more reactive toward oxygens than are dialkylsulfates and alkylalkanesulfonates. The ratio of N : O alkyl products is strongly pH dependent, primarily due to the N-3 being most reactive at the higher pH values, while the diester is most reactive at the lower pH values. The extent of reaction of the O2, O4 or 2'-O or ribose is not greatly affected over the pH range tested. At pH 5.0 alkyl ribophosphotriesters mainly lose  alchol to re-form a stable phosphodiester. With increasing OH- concentration, the favored reaction is chain scission at the 3'-O-P bond.", "contents": "Sites of alkylation of poly(U) by agents of varying carcinogenicity and stability of products. Several alkylating agents of widely varying reported carcinogenicity (dimethylsulfate, diethylsulfate, ethylmethanesulfonate, methylnitrosourea, ethylnitrosourea and ethylnitrosoguanidine) were reacted with poly(U) at pH values ranging from 4.5 to 7.5. All nucleophilic centers (internal phosphate groups, ribose hydroxyls, and O2, N-3 and O4 sites of the uracil base) were found reactive, though to different extents, at neutrality and in slightly acid solution. The distribution of products is a function of the alkylating agent and pH. The nitroso compounds are more reactive toward oxygens than are dialkylsulfates and alkylalkanesulfonates. The ratio of N : O alkyl products is strongly pH dependent, primarily due to the N-3 being most reactive at the higher pH values, while the diester is most reactive at the lower pH values. The extent of reaction of the O2, O4 or 2'-O or ribose is not greatly affected over the pH range tested. At pH 5.0 alkyl ribophosphotriesters mainly lose  alchol to re-form a stable phosphodiester. With increasing OH- concentration, the favored reaction is chain scission at the 3'-O-P bond."}
{"id": "PMID:9142", "title": "Mode of orthophosphate uptake and ATP labeling by mammalian cells.", "content": "Incubation of HeLa cells with [32P]orthophosphate results in more rapid labeling of the gamma-phosphorus of ATP than of the intracellular pool of orthophosphate. The specific radioactivity of ATP equals that of extracellular orthophosphate after 2 h of incubation. A similar pattern of labeling is seen with human erythrocytes when incubated at physiological concentrations of orthophosphate (2 mM) and pH 7.4-7.8. At lower pH, 6.8-7.2, the rate of orthophosphate uptake increases and exceeds the rate of labeling of ATP. These data are explained by the existence of a primary system for ATP uptake which involves the mediation of membrane-bound glyceraldehyde-3-phosphate dehydrogenase. Phosphate first enters the cell as 1,3-diphosphoglyceric acid, is then transferred to ATP, and then enters the intracellular orthophosphate pool. At lower pH monovalent orthophosphate also enters the erythrocyte by a process not involving glyceraldehyde-3-phosphate dehydrogenase.", "contents": "Mode of orthophosphate uptake and ATP labeling by mammalian cells. Incubation of HeLa cells with [32P]orthophosphate results in more rapid labeling of the gamma-phosphorus of ATP than of the intracellular pool of orthophosphate. The specific radioactivity of ATP equals that of extracellular orthophosphate after 2 h of incubation. A similar pattern of labeling is seen with human erythrocytes when incubated at physiological concentrations of orthophosphate (2 mM) and pH 7.4-7.8. At lower pH, 6.8-7.2, the rate of orthophosphate uptake increases and exceeds the rate of labeling of ATP. These data are explained by the existence of a primary system for ATP uptake which involves the mediation of membrane-bound glyceraldehyde-3-phosphate dehydrogenase. Phosphate first enters the cell as 1,3-diphosphoglyceric acid, is then transferred to ATP, and then enters the intracellular orthophosphate pool. At lower pH monovalent orthophosphate also enters the erythrocyte by a process not involving glyceraldehyde-3-phosphate dehydrogenase."}
{"id": "PMID:9143", "title": "Studies on the phosphorylated intermediates of a K+-stimulated ATPase from rabbit gastric mucosa.", "content": "A density gradient-purified microsomal membrane preparation from rabbit fundic gastric mucosa was used for a detailed study of the K+-stimulated ATPase and associated intermediate reactions. Membranes incubated with gamma-[32P]ATP show the rapid incorporation of 32P into phosphoprotein. Phosphoprotein levels were markedly reduced (1) when ATP hydrolysis went to completion or (2) upon addition of unlabeled ATP, thus suggesting the participation of a rapid turnover phosphorylated intermediate in the gastric microsomal ATPase. Addition of K+, Rb+ or Tl+ greatly reduced the level of the intermediate while stimulating ATPase activity; the observed affinities of these cations were similar for the effects on both ATPase and intermediate levels, with Tl+ greater than K+ greater than Rb+. Neither ATPase nor intermediate were stimulated by Na+, and ouabain was without effect on the reactions, thus differentiating this system from the (Na+ + K+)-ATPase. Addition of various inhibitors showed differential effects on the partial reactions of the gastric ATPase system. N-ethylmaleimide and Zn2+ showed characteristics of completely abolishing the K+-stimulated component of ATPase as well as the effects of K+ in reducing the level of intermediate, thus suggesting that these agents exert their inhibitory effect on a phosphoprotein phosphatase partial reaction. F- abolished the K+-stimulated ATPase, but its more complex effects on the intermediate suggested an additional reaction step within the domain of the phosphorylated intermediate. Results are consistent with a model system for the gastric microsomal ATPase involving a Mg2+-dependent protein kinase, a phosphorylated intermediate(s), and a K+-stimulated phosphoprotein phosphatase.", "contents": "Studies on the phosphorylated intermediates of a K+-stimulated ATPase from rabbit gastric mucosa. A density gradient-purified microsomal membrane preparation from rabbit fundic gastric mucosa was used for a detailed study of the K+-stimulated ATPase and associated intermediate reactions. Membranes incubated with gamma-[32P]ATP show the rapid incorporation of 32P into phosphoprotein. Phosphoprotein levels were markedly reduced (1) when ATP hydrolysis went to completion or (2) upon addition of unlabeled ATP, thus suggesting the participation of a rapid turnover phosphorylated intermediate in the gastric microsomal ATPase. Addition of K+, Rb+ or Tl+ greatly reduced the level of the intermediate while stimulating ATPase activity; the observed affinities of these cations were similar for the effects on both ATPase and intermediate levels, with Tl+ greater than K+ greater than Rb+. Neither ATPase nor intermediate were stimulated by Na+, and ouabain was without effect on the reactions, thus differentiating this system from the (Na+ + K+)-ATPase. Addition of various inhibitors showed differential effects on the partial reactions of the gastric ATPase system. N-ethylmaleimide and Zn2+ showed characteristics of completely abolishing the K+-stimulated component of ATPase as well as the effects of K+ in reducing the level of intermediate, thus suggesting that these agents exert their inhibitory effect on a phosphoprotein phosphatase partial reaction. F- abolished the K+-stimulated ATPase, but its more complex effects on the intermediate suggested an additional reaction step within the domain of the phosphorylated intermediate. Results are consistent with a model system for the gastric microsomal ATPase involving a Mg2+-dependent protein kinase, a phosphorylated intermediate(s), and a K+-stimulated phosphoprotein phosphatase."}
{"id": "PMID:9144", "title": "Isolation of calcium pump system and purification of calcium ion-dependent ATPase from heart muscle.", "content": "The procedure for the isolation of the highly active fraction of sarcoplasmic reticulum from pigeon and dog hearts is described. The method is based on the partial loading of heart microsomes with calcium and oxalate ions and the precipitation of loaded vesicles in sucrose and potassium chloride concentration gradients. Preparations obtained possess high activity of Ca2+-dependent ATPase and are also able to accumulate up to 10 mumol Ca2+ per mg protein. Purification of sarcoplasmic reticulum membranes is accompanied by a decrease in concentration of cytochrome a+a3 and an increase in the content of [32P]phosphoenzyme. The basic components in \"calcium-oxalate preparation\" from hearts are proteins with molecular weights of about 100000 (Ca2+-dependent ATPase) and 55000 Calcium-oxalate preparation from pigeon hearts was used for subsequent purification of Ca2+-dependent ATPase. Specific activity of purified enzyme from pigeon hearts is 12-16 mumol Pi/min per mg protein. Enzyme activity of purified Ca2+-dependent ATPase is inhibited by EGTA and is not sensitive to azide, 2,4-dinitrophenol and ouabain. The data obtained demonstrate the similarity of calcium pump systems and Ca2+-dependent ATPases isolated from heart and skeletal muscles.", "contents": "Isolation of calcium pump system and purification of calcium ion-dependent ATPase from heart muscle. The procedure for the isolation of the highly active fraction of sarcoplasmic reticulum from pigeon and dog hearts is described. The method is based on the partial loading of heart microsomes with calcium and oxalate ions and the precipitation of loaded vesicles in sucrose and potassium chloride concentration gradients. Preparations obtained possess high activity of Ca2+-dependent ATPase and are also able to accumulate up to 10 mumol Ca2+ per mg protein. Purification of sarcoplasmic reticulum membranes is accompanied by a decrease in concentration of cytochrome a+a3 and an increase in the content of [32P]phosphoenzyme. The basic components in \"calcium-oxalate preparation\" from hearts are proteins with molecular weights of about 100000 (Ca2+-dependent ATPase) and 55000 Calcium-oxalate preparation from pigeon hearts was used for subsequent purification of Ca2+-dependent ATPase. Specific activity of purified enzyme from pigeon hearts is 12-16 mumol Pi/min per mg protein. Enzyme activity of purified Ca2+-dependent ATPase is inhibited by EGTA and is not sensitive to azide, 2,4-dinitrophenol and ouabain. The data obtained demonstrate the similarity of calcium pump systems and Ca2+-dependent ATPases isolated from heart and skeletal muscles."}
{"id": "PMID:9146", "title": "Biological activity of agarose-immobilized catecholamines.", "content": "Catecholamines substituted to agarose were synthesized in various ways. Norepinephrine and isoproterenol were linked to p-aminobenzamidohexyl agarose by an azo linkage to the catechol ring. Norepinephrine was also couple to hexyl agaros via the amino group, forming an amino, guanidino or amido bond. Biological activity of the immobilized catecholamines was determined by assessing their abilities to interact with adenylate cyclase in several membrane preparations and intact preparations of erythrocytes. In dog heart membranes, stimulation of adenylate cyclase by the catecholamine-gels could be accounted for by leached hormone which had been released from the gels. In frog erythrocyte membranes, leaching was minimal and no significant stimulation of adenylate cyclase was observed. Agarose-immobilized catecholamines, however, competitively inhibited isoproterenol stimulation of adenylate cyclase in these erythrocyte membranes indicating that catecholamines which are bound to agarose interact with the beta-adrenergic receptors as antagonists rather than agonists. When tested on intact frog erythrocytes, agarose immobilzed catecholamines did not increase the intracellular levels of cyclic AMP, although isoproterenol caused as 8-10 fold rise in these levels. Similarly, when tested for antagonist activity in the intact cells the agarose-catecholamines failed to inhibit the stimulation of cyclic AMP caused by isoproterenol. The difference observed in the beta-adrenergic antagonist activity of the agarose-bound catecholamines in membrane preparations and intact cells can be attributed to steric factors which could have prevented the access of the bead-bound ligands with the surface of the cell or to the possibility that receptors might be buried in the membrane matrix.", "contents": "Biological activity of agarose-immobilized catecholamines. Catecholamines substituted to agarose were synthesized in various ways. Norepinephrine and isoproterenol were linked to p-aminobenzamidohexyl agarose by an azo linkage to the catechol ring. Norepinephrine was also couple to hexyl agaros via the amino group, forming an amino, guanidino or amido bond. Biological activity of the immobilized catecholamines was determined by assessing their abilities to interact with adenylate cyclase in several membrane preparations and intact preparations of erythrocytes. In dog heart membranes, stimulation of adenylate cyclase by the catecholamine-gels could be accounted for by leached hormone which had been released from the gels. In frog erythrocyte membranes, leaching was minimal and no significant stimulation of adenylate cyclase was observed. Agarose-immobilized catecholamines, however, competitively inhibited isoproterenol stimulation of adenylate cyclase in these erythrocyte membranes indicating that catecholamines which are bound to agarose interact with the beta-adrenergic receptors as antagonists rather than agonists. When tested on intact frog erythrocytes, agarose immobilzed catecholamines did not increase the intracellular levels of cyclic AMP, although isoproterenol caused as 8-10 fold rise in these levels. Similarly, when tested for antagonist activity in the intact cells the agarose-catecholamines failed to inhibit the stimulation of cyclic AMP caused by isoproterenol. The difference observed in the beta-adrenergic antagonist activity of the agarose-bound catecholamines in membrane preparations and intact cells can be attributed to steric factors which could have prevented the access of the bead-bound ligands with the surface of the cell or to the possibility that receptors might be buried in the membrane matrix."}
{"id": "PMID:9147", "title": "Subcellular distribution and properties of guanylate cyclase in rat cerebellum.", "content": "In rat cerebellum the major portion of guanylate cyclase was found to be particulate-bound. The properties of particulate and supernatant guanylate cyclases from the cerebellum were comparatively examined. Both enzymes required the same optimal concentration of Mn2+ and were stimulated by Ca2+ in the presence of a low concentration of Mn2+. But dispersion of the particulate enzyme with Triton X-100 altered the Mn2+ concentration producing maximum activity and the inhibitory effect of Ca2+. The subcellular distributions of guanylate and adenylate cyclases were also studied in rat cerebellum. The major portions of the two cyclases were found in the mitochondrial fraction. The submitochondrial fractions separated by sucrose gradient showed that the major activities of both cyclases were concentrated in the fraction containing mainly nerve ending particles.", "contents": "Subcellular distribution and properties of guanylate cyclase in rat cerebellum. In rat cerebellum the major portion of guanylate cyclase was found to be particulate-bound. The properties of particulate and supernatant guanylate cyclases from the cerebellum were comparatively examined. Both enzymes required the same optimal concentration of Mn2+ and were stimulated by Ca2+ in the presence of a low concentration of Mn2+. But dispersion of the particulate enzyme with Triton X-100 altered the Mn2+ concentration producing maximum activity and the inhibitory effect of Ca2+. The subcellular distributions of guanylate and adenylate cyclases were also studied in rat cerebellum. The major portions of the two cyclases were found in the mitochondrial fraction. The submitochondrial fractions separated by sucrose gradient showed that the major activities of both cyclases were concentrated in the fraction containing mainly nerve ending particles."}
{"id": "PMID:9148", "title": "Studies on cyclic nucleotides in cancer. I. Adenylate guanylate cyclase and protein kinases in the prostatic sarcoma tissue.", "content": "Adenylate, guanylate cyclase and protein kinases in a fibrous sarcoma originating from rat prostate have been studied. A decrease in levels of adenosine 3', 5'-monophosphate (cyclic AMP) and adenylate cyclase activities and an increase in levels of guanosine 3',5'-monophosphate (cyclic GMP) and guanylate cyclase activities were observed in the tumor tissue when compared with the normal prostatic tissue of rats. Protein kinases from the tumor and the prostate were both responsive to exogenous cyclic AMP, with an apparent Ka of 0.08 muM in the tumor and of 0.11 muM in the prostate. It is of interest that the protein kinases from the tumor responded to cyclic AMP to the same extent as was observed in the enzyme preparation from the prostate. The protein kinase from the tumor was more sensitive to cyclic GMP than that from the prostate, showing an apparent Ka of 0.88 muM in the tumor and of 4.85 muM in the prostate. This tumor has been characterized with an increase in guanylate cyclase activities with a subsequent rise in cellular cyclic GMP and an increased sensitivity of the protein kinase to cyclic GMP.", "contents": "Studies on cyclic nucleotides in cancer. I. Adenylate guanylate cyclase and protein kinases in the prostatic sarcoma tissue. Adenylate, guanylate cyclase and protein kinases in a fibrous sarcoma originating from rat prostate have been studied. A decrease in levels of adenosine 3', 5'-monophosphate (cyclic AMP) and adenylate cyclase activities and an increase in levels of guanosine 3',5'-monophosphate (cyclic GMP) and guanylate cyclase activities were observed in the tumor tissue when compared with the normal prostatic tissue of rats. Protein kinases from the tumor and the prostate were both responsive to exogenous cyclic AMP, with an apparent Ka of 0.08 muM in the tumor and of 0.11 muM in the prostate. It is of interest that the protein kinases from the tumor responded to cyclic AMP to the same extent as was observed in the enzyme preparation from the prostate. The protein kinase from the tumor was more sensitive to cyclic GMP than that from the prostate, showing an apparent Ka of 0.88 muM in the tumor and of 4.85 muM in the prostate. This tumor has been characterized with an increase in guanylate cyclase activities with a subsequent rise in cellular cyclic GMP and an increased sensitivity of the protein kinase to cyclic GMP."}
{"id": "PMID:9149", "title": "Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes.", "content": "The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the \"release\" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels.", "contents": "Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes. The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the \"release\" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels."}
{"id": "PMID:9150", "title": "Images of divalent cations in unstained symmetric and asymmetric lipid bilayers.", "content": "Divalent cations have been microscopiccally visualized in association with simple lipid bilayers. Symmetric and asymmetric oriented bilayers were constructed from fatty acid monolayers and were cut in thin transverse sections for examination by bright field electron microscopy in the absence of stains, fixatives or embedding materials. It has been found that bilayers formed of lipid molecules having alkaline earth head groups exhibit natural electron contrast. The intrinsic image has been liked to local variations in the bilayer absolute electron density profile determined by X-ray diffraction analysis of the same specimens (McIntosh, T. J., Waldbillig, R. C. and Robertson, J. D. (1976) Biochim. Biophys. Acta 448, 15-33). By combining the microscopic, chemical and X-ray evidence it has been estimated that local increments of about 1 g/cm3 can produce detectable elelcron contrast in 500 A transverse sections of bilayers.", "contents": "Images of divalent cations in unstained symmetric and asymmetric lipid bilayers. Divalent cations have been microscopiccally visualized in association with simple lipid bilayers. Symmetric and asymmetric oriented bilayers were constructed from fatty acid monolayers and were cut in thin transverse sections for examination by bright field electron microscopy in the absence of stains, fixatives or embedding materials. It has been found that bilayers formed of lipid molecules having alkaline earth head groups exhibit natural electron contrast. The intrinsic image has been liked to local variations in the bilayer absolute electron density profile determined by X-ray diffraction analysis of the same specimens (McIntosh, T. J., Waldbillig, R. C. and Robertson, J. D. (1976) Biochim. Biophys. Acta 448, 15-33). By combining the microscopic, chemical and X-ray evidence it has been estimated that local increments of about 1 g/cm3 can produce detectable elelcron contrast in 500 A transverse sections of bilayers."}
{"id": "PMID:9151", "title": "The interaction of magnesium ions with the calcium pump of sarcoplasmic reticulum.", "content": "1. In the presence of Ca2+, ATP phosphorylates the Ca2+ pump of sarcoplasmic reticulum at the same site and to the same extent regardless of whether Mg2+ is added or not to the incubation media, the main effect of added Mg2+ being to increase the rate of phosphorylation. 2. When phosphoenzyme is made in Mg2+-containing media it dephosphorylates about 30-times faster than when it is made in the absence of added Mg2+. Addition of Mg2+ after phosphorylation is uneffective in accelerating the hydrolysis of phosphoenzyme even in solubilized enzyme, suggesting that phosphorylation of the Ca2+ pump results in occlusion of the site at which Mg2+ combines to accelerate the release of phosphate. 3. Occlusion of the site for Mg2+ can be partially reversed by trans-1,2-diaminocyclohexonetetraacetic acid (CDTA). Use was made of this property to demonstrate that for the rapid release of phosphate to occur Mg2+ has to be bound to the enzyme. 4. Results seem to indicate that Mg2+ combines with the Ca2+ pump prior to phosphorylation.", "contents": "The interaction of magnesium ions with the calcium pump of sarcoplasmic reticulum. 1. In the presence of Ca2+, ATP phosphorylates the Ca2+ pump of sarcoplasmic reticulum at the same site and to the same extent regardless of whether Mg2+ is added or not to the incubation media, the main effect of added Mg2+ being to increase the rate of phosphorylation. 2. When phosphoenzyme is made in Mg2+-containing media it dephosphorylates about 30-times faster than when it is made in the absence of added Mg2+. Addition of Mg2+ after phosphorylation is uneffective in accelerating the hydrolysis of phosphoenzyme even in solubilized enzyme, suggesting that phosphorylation of the Ca2+ pump results in occlusion of the site at which Mg2+ combines to accelerate the release of phosphate. 3. Occlusion of the site for Mg2+ can be partially reversed by trans-1,2-diaminocyclohexonetetraacetic acid (CDTA). Use was made of this property to demonstrate that for the rapid release of phosphate to occur Mg2+ has to be bound to the enzyme. 4. Results seem to indicate that Mg2+ combines with the Ca2+ pump prior to phosphorylation."}
{"id": "PMID:9152", "title": "Different proton-sugar stoichiometries for the uptake of glucose analogues by Chlorella vulgaris. Evidence for sugar-dependent proton uptake without concomitant sugar uptake by the proton-sugar symport system.", "content": "The uptake of hexoses by Chlorella vulgaris is accompanied by the uptake of protons. For 6-deoxyglucose a stoichiometry of one proton taken up per sugar molecule has been measured, whereas for 1-deoxyglucose approximately two protons are taken up per sugar molecule. It was found that in the presence of 1-deoxyglucose a considerable proportion of \"carrier\" catalyzes the transport of protons without the concomitant transport of sugar. Presumably, the binding of sugar initiates the translocation of the carrier-proton-sugar complex, but whereas 1-deoxyglucose can still dissociate from the complex at the external side of the cytoplasmic membrane, the translocation of the carrier-proton complex continues. This conclusion was reached since (a) the composition of the translocated carrier-proton-sugar complex is the same for both sugar. Its formation is a first order reaction with respect to protons. (b) When 6-deoxyglucose, present inside cells, is exchanged for external sugar, the exchange ratio is two to one when the external sugar is 1-deoxyglucose, two molecules of 6-deoxyglucose are lost for each molecule of 1-deoxyglucose entering. This result indicates that during uptake of 1-deoxyglucose statistically only each second carrier molecule appearing at the internal side of the cytoplasmic membrane is carrying sugar.", "contents": "Different proton-sugar stoichiometries for the uptake of glucose analogues by Chlorella vulgaris. Evidence for sugar-dependent proton uptake without concomitant sugar uptake by the proton-sugar symport system. The uptake of hexoses by Chlorella vulgaris is accompanied by the uptake of protons. For 6-deoxyglucose a stoichiometry of one proton taken up per sugar molecule has been measured, whereas for 1-deoxyglucose approximately two protons are taken up per sugar molecule. It was found that in the presence of 1-deoxyglucose a considerable proportion of \"carrier\" catalyzes the transport of protons without the concomitant transport of sugar. Presumably, the binding of sugar initiates the translocation of the carrier-proton-sugar complex, but whereas 1-deoxyglucose can still dissociate from the complex at the external side of the cytoplasmic membrane, the translocation of the carrier-proton complex continues. This conclusion was reached since (a) the composition of the translocated carrier-proton-sugar complex is the same for both sugar. Its formation is a first order reaction with respect to protons. (b) When 6-deoxyglucose, present inside cells, is exchanged for external sugar, the exchange ratio is two to one when the external sugar is 1-deoxyglucose, two molecules of 6-deoxyglucose are lost for each molecule of 1-deoxyglucose entering. This result indicates that during uptake of 1-deoxyglucose statistically only each second carrier molecule appearing at the internal side of the cytoplasmic membrane is carrying sugar."}
{"id": "PMID:9153", "title": "Lipid bilayer ultrastructure. Electron density profiles and chain tilt angles as determined by X-ray diffraction.", "content": "High resolution (6A) electron density profiles have been computed on an absolute electron density scale for bilayers composed of both saturated fatty acids and fatty acids associated with the alkaline earth series of divalent cations. Lowangle X-ray diffraction data have been interpreted by an isomorphous replacement technique. The position on the X-ray film of discrete wide-angle reflections has provided direct information on the hydrocarbon chain packing and chain tilt in these bilayers. These results have been correlated to an electron microscopy study of the same bilayers (Waldbilling, R. C., Robertson, J.D. and McIntosh, T. J. (1976) Biochim. Biophys. Acta 448, 1-14) and also to X-ray diffraction studies of fatty acid crystals. A method for forming and structurally analyzing bilayers of well defined chemical asymmetry is also described.", "contents": "Lipid bilayer ultrastructure. Electron density profiles and chain tilt angles as determined by X-ray diffraction. High resolution (6A) electron density profiles have been computed on an absolute electron density scale for bilayers composed of both saturated fatty acids and fatty acids associated with the alkaline earth series of divalent cations. Lowangle X-ray diffraction data have been interpreted by an isomorphous replacement technique. The position on the X-ray film of discrete wide-angle reflections has provided direct information on the hydrocarbon chain packing and chain tilt in these bilayers. These results have been correlated to an electron microscopy study of the same bilayers (Waldbilling, R. C., Robertson, J.D. and McIntosh, T. J. (1976) Biochim. Biophys. Acta 448, 1-14) and also to X-ray diffraction studies of fatty acid crystals. A method for forming and structurally analyzing bilayers of well defined chemical asymmetry is also described."}
{"id": "PMID:9154", "title": "Passive potassium ion permeability of Halobacterium halobium cell envelope membranes.", "content": "Cell envelope vesicles, prepared from Halobacterium halobium, were loaded with 3 M KCl, suspended in 3 M NaCl, and the loss of K+ was followed at various temperatures. The Arrhenius plot of the K+-efflux rates shows a break at 30 degrees C, with higher energy of activation above the break. This temperature dependence is consistent with earlier studies of chain motions in liposomes prepared from isolated lipids. The efflux of K+ is more rapid with increasing pH between pH 5 and 7. Since these vesicles do not respire under the experimental conditions it was expected that the K+-efflux data would be related to the passive permeability of the membranes to K+. The apparent K+ permeability at 30 degrees C is 1--2 - 10(-10) cm - s-1. This value corresponds to a 5-h half-life for retained K+ in the envelope vesicles and to a probably much longer half-life in whole cells. The previously observed ability of Halobacterium to retain K+ in the absence of metabolism can thus be explained solely by the permeability characteristics of the membranes.", "contents": "Passive potassium ion permeability of Halobacterium halobium cell envelope membranes. Cell envelope vesicles, prepared from Halobacterium halobium, were loaded with 3 M KCl, suspended in 3 M NaCl, and the loss of K+ was followed at various temperatures. The Arrhenius plot of the K+-efflux rates shows a break at 30 degrees C, with higher energy of activation above the break. This temperature dependence is consistent with earlier studies of chain motions in liposomes prepared from isolated lipids. The efflux of K+ is more rapid with increasing pH between pH 5 and 7. Since these vesicles do not respire under the experimental conditions it was expected that the K+-efflux data would be related to the passive permeability of the membranes to K+. The apparent K+ permeability at 30 degrees C is 1--2 - 10(-10) cm - s-1. This value corresponds to a 5-h half-life for retained K+ in the envelope vesicles and to a probably much longer half-life in whole cells. The previously observed ability of Halobacterium to retain K+ in the absence of metabolism can thus be explained solely by the permeability characteristics of the membranes."}
{"id": "PMID:9155", "title": "The interaction of radioiodinated thyrotropin with plasma membranes. Evidence for high affinity binding sites in the thyroid.", "content": "The binding of biologically active [125I]thyrotropin to purified plasma membranes prepared from bovine thyroid glands was studied. At 4 degrees C, specific binding reached a maximum after 2 h of incubation and a plateau was maintained for up to 20 h. Degradation of [125I]thyrotropin was undetectable after 2 h of incubation and was only 10% of the total after 20 h. At pH 6.0, at which binding was maximal, a single class of binding sites, having a dissociation constant of approx. 25 nM, was evident. Dissociation studies revealed first order kinetics with a half-time of 2-3 min. At pH 7.5, binding curves were complex, suggesting two orders of binding sites with dissociation constants of approx. 200 nM and 80 pM. Further, at this pH, dissociation of the thyrotropin from its receptor was also complex, suggesting the presence of two first order reactions, one with a half-time similar to that seen at pH 6.0 and another with a half-time of 4 h. At both pH 6.0 and 7.5, insulin, glucagon, growth hormone, and prolactin were without effect on [125I]thyrotropin binding. Similar high affinity and low affinity binding sites were seen with porcine thyroid membranes, but only low affinity sites were seen with either rat liver membranes or human cultured lymphocytes.", "contents": "The interaction of radioiodinated thyrotropin with plasma membranes. Evidence for high affinity binding sites in the thyroid. The binding of biologically active [125I]thyrotropin to purified plasma membranes prepared from bovine thyroid glands was studied. At 4 degrees C, specific binding reached a maximum after 2 h of incubation and a plateau was maintained for up to 20 h. Degradation of [125I]thyrotropin was undetectable after 2 h of incubation and was only 10% of the total after 20 h. At pH 6.0, at which binding was maximal, a single class of binding sites, having a dissociation constant of approx. 25 nM, was evident. Dissociation studies revealed first order kinetics with a half-time of 2-3 min. At pH 7.5, binding curves were complex, suggesting two orders of binding sites with dissociation constants of approx. 200 nM and 80 pM. Further, at this pH, dissociation of the thyrotropin from its receptor was also complex, suggesting the presence of two first order reactions, one with a half-time similar to that seen at pH 6.0 and another with a half-time of 4 h. At both pH 6.0 and 7.5, insulin, glucagon, growth hormone, and prolactin were without effect on [125I]thyrotropin binding. Similar high affinity and low affinity binding sites were seen with porcine thyroid membranes, but only low affinity sites were seen with either rat liver membranes or human cultured lymphocytes."}
{"id": "PMID:9156", "title": "Relationship between medium pH and that of the lysosomal matrix as studied by two independent methods.", "content": "1. The method of estimating the intralysosomal pH by measuring the distribution of [14C]methylamine in lysosomes isolated from the livers of Triton WR 1339-treated rats has been critically examined. 2. In lysed lysosomes, methylamine is bound to the membrane fragments, but this binding can be completely suppressed by increasing the concentration of monovalent cations in the medium. 3. In intact lysosomes, the binding of [14C]methylamine is only partly inhibited by monovalent cations at 25 degrees C. 4. THe accumulation of [14C]methylamine in intact lysosomes is progressively inhibited as the concentration of methylamine is increased. A similar inhibition of [14C]methylamine accumulation is obtained with NH4Cl. 5. Similar values for the intralysosomal pH were obtained from measurements of the distribution of methylamine, dimethylamine and trimethylamine, which are accumulated in the lysosomes, and of 5,5-dimethyloxazolidinedione-2,4, which is excluded. 6. The breakdown of endocytosed 123I-labelled bovine serum albumin by intact isolated lysosomes is much less sensitive to the pH of the medium than the breakdown of added protein by lysed lysosomes. 7. The intralysosomal pH has been estimated by comparing the rate of breakdown of endocytosed 125I-labelled albumin in intact lysosomes as a function of medium pH with that of added 125I-labelled albumin by lysed lysosomes at different pH values. The values obtained agree well with those calculated from the distribution of [14C]methylamine. 8. Methylamine and NH4Cl inhibit the breakdown of 125I-labelled albumin in intact lysosomes, particularly at high medium pH, but have no effect on the breakdown by lysed lysosomes. 9. It is concluded that a pH difference across the lysosomal membrane (more acidic inside than outside) is maintained by the presence of indiffusible negatively charged groups within the lysosomes, and by the permeation across the lysosomal membrane of protons together with permeant anions (or of OH- in exchange for anions).", "contents": "Relationship between medium pH and that of the lysosomal matrix as studied by two independent methods. 1. The method of estimating the intralysosomal pH by measuring the distribution of [14C]methylamine in lysosomes isolated from the livers of Triton WR 1339-treated rats has been critically examined. 2. In lysed lysosomes, methylamine is bound to the membrane fragments, but this binding can be completely suppressed by increasing the concentration of monovalent cations in the medium. 3. In intact lysosomes, the binding of [14C]methylamine is only partly inhibited by monovalent cations at 25 degrees C. 4. THe accumulation of [14C]methylamine in intact lysosomes is progressively inhibited as the concentration of methylamine is increased. A similar inhibition of [14C]methylamine accumulation is obtained with NH4Cl. 5. Similar values for the intralysosomal pH were obtained from measurements of the distribution of methylamine, dimethylamine and trimethylamine, which are accumulated in the lysosomes, and of 5,5-dimethyloxazolidinedione-2,4, which is excluded. 6. The breakdown of endocytosed 123I-labelled bovine serum albumin by intact isolated lysosomes is much less sensitive to the pH of the medium than the breakdown of added protein by lysed lysosomes. 7. The intralysosomal pH has been estimated by comparing the rate of breakdown of endocytosed 125I-labelled albumin in intact lysosomes as a function of medium pH with that of added 125I-labelled albumin by lysed lysosomes at different pH values. The values obtained agree well with those calculated from the distribution of [14C]methylamine. 8. Methylamine and NH4Cl inhibit the breakdown of 125I-labelled albumin in intact lysosomes, particularly at high medium pH, but have no effect on the breakdown by lysed lysosomes. 9. It is concluded that a pH difference across the lysosomal membrane (more acidic inside than outside) is maintained by the presence of indiffusible negatively charged groups within the lysosomes, and by the permeation across the lysosomal membrane of protons together with permeant anions (or of OH- in exchange for anions)."}
{"id": "PMID:9157", "title": "Protein kinases associated with peripheral nerve myelin. 1. Phosphorylation of endogenous myelin proteins and exogenous substrates.", "content": "When highly purified myelin from rat sciatic nerve was incubated with [gamma-32P]ATP, protein components of the membrane were phosphorylated indicating the presence of both the substrate (receptor protein) and an endogenous kinase in the membrane. Polyacrylamide gel electrophoresis of the phosphorylated membrane proteins followed by scintillation counting of gel slices and autoradiography showed that the polypeptides of molecular weights 28000, 23000 and 19000 were phosphorylated, and 32P from [gamma-32P]ATP having been incorporated into serine residues of the substrate proteins. Phosphorylation of purified myelin was Mg2+-dependent, was optimal at pH 6.5 and was not stimulated by adenosine 3',5'-monophosphate. We found that proteins other than those in myelin, such as phosvitin, casein, protamine and histones, can also act as a substrate for the membrane associated kinase. Muscle protein kinase inhibitor had no effect on the endogenous phosphorylation of myelin proteins or on the phosphorylation of phosvitin by peripheral nerve myelin protein kinase. However, the phosphorylation of histone by peripheral nerve myelin protein kinase was inhibited by the protein kinase inhibitor. After washing the membrane with 150 mM KCl the protein kinase that utilizes histone as substrate was found in the supernatant. In contrast, the endogenous phosphorylation of membrane proteins or the phosphorylation of phosvitin by the membrane associated kinase was not affected by washing. From these findings we conclude that at least two protein kinase systems exist in purified peripheral nerve myelin. One system is not inhibited by muscle kinase inhibitor, is tightly bound to the membrane and utilizes as its receptor proteins either exogenous phosvitin or endogenous membrane proteins. The second system is inhibited by muscle kinase inhibitor, is removable from the membrane and utilizes histones as its receptor proteins.", "contents": "Protein kinases associated with peripheral nerve myelin. 1. Phosphorylation of endogenous myelin proteins and exogenous substrates. When highly purified myelin from rat sciatic nerve was incubated with [gamma-32P]ATP, protein components of the membrane were phosphorylated indicating the presence of both the substrate (receptor protein) and an endogenous kinase in the membrane. Polyacrylamide gel electrophoresis of the phosphorylated membrane proteins followed by scintillation counting of gel slices and autoradiography showed that the polypeptides of molecular weights 28000, 23000 and 19000 were phosphorylated, and 32P from [gamma-32P]ATP having been incorporated into serine residues of the substrate proteins. Phosphorylation of purified myelin was Mg2+-dependent, was optimal at pH 6.5 and was not stimulated by adenosine 3',5'-monophosphate. We found that proteins other than those in myelin, such as phosvitin, casein, protamine and histones, can also act as a substrate for the membrane associated kinase. Muscle protein kinase inhibitor had no effect on the endogenous phosphorylation of myelin proteins or on the phosphorylation of phosvitin by peripheral nerve myelin protein kinase. However, the phosphorylation of histone by peripheral nerve myelin protein kinase was inhibited by the protein kinase inhibitor. After washing the membrane with 150 mM KCl the protein kinase that utilizes histone as substrate was found in the supernatant. In contrast, the endogenous phosphorylation of membrane proteins or the phosphorylation of phosvitin by the membrane associated kinase was not affected by washing. From these findings we conclude that at least two protein kinase systems exist in purified peripheral nerve myelin. One system is not inhibited by muscle kinase inhibitor, is tightly bound to the membrane and utilizes as its receptor proteins either exogenous phosvitin or endogenous membrane proteins. The second system is inhibited by muscle kinase inhibitor, is removable from the membrane and utilizes histones as its receptor proteins."}
{"id": "PMID:9158", "title": "Biochemical studies of the excitable membrane of Paramecium aurelia. I. 45Ca2+ fluxes across resting and excited membrane.", "content": "The characteristics of Ca2+ transport across the excitable membrane of Paramecium aurelia were studied by measuring 45Ca2+ influx and efflux. The intracellular concentration of free Ca2+ in resting P. aurelia was at least ten times less than the extracellular concentration. Ca2+ influx was easily measurable at 0 degrees C, but not at 23 degrees C. The influx of 45Ca2+ was stimulated by the same conditions which cause membrane depolarization and ciliary reversal. Addition of Na+ and K+ (which stimulate ciliary reversal) resulted in a 10-fold increase in the rate of Ca2+ influx. An externally applied, pulsed, electric field (1-2 mA/cm2 of electrode surface), caused the rate of Ca2+ influx to increase 3-5 times, with the extent of stimulation dependent on the current density and the pulse width. Ca2+ influx had the characteristics of a passive transport system and was associated with the chemically or electrically triggered Ca2+ \"gating\" mechanism, which has been studied electrophysiologically. In contrast, Ca2+ efflux appeared to be catalyzed by an active transport system. With cells previously loaded at 0 degrees C with 45Ca2+, Ca2+ efflux was rapid at 23 degrees C, but did not occur at 0 degrees C. This active Ca2+ efflux mechanism is probably responsible for maintaining the low internal Ca2+ levels in unstimulated cells.", "contents": "Biochemical studies of the excitable membrane of Paramecium aurelia. I. 45Ca2+ fluxes across resting and excited membrane. The characteristics of Ca2+ transport across the excitable membrane of Paramecium aurelia were studied by measuring 45Ca2+ influx and efflux. The intracellular concentration of free Ca2+ in resting P. aurelia was at least ten times less than the extracellular concentration. Ca2+ influx was easily measurable at 0 degrees C, but not at 23 degrees C. The influx of 45Ca2+ was stimulated by the same conditions which cause membrane depolarization and ciliary reversal. Addition of Na+ and K+ (which stimulate ciliary reversal) resulted in a 10-fold increase in the rate of Ca2+ influx. An externally applied, pulsed, electric field (1-2 mA/cm2 of electrode surface), caused the rate of Ca2+ influx to increase 3-5 times, with the extent of stimulation dependent on the current density and the pulse width. Ca2+ influx had the characteristics of a passive transport system and was associated with the chemically or electrically triggered Ca2+ \"gating\" mechanism, which has been studied electrophysiologically. In contrast, Ca2+ efflux appeared to be catalyzed by an active transport system. With cells previously loaded at 0 degrees C with 45Ca2+, Ca2+ efflux was rapid at 23 degrees C, but did not occur at 0 degrees C. This active Ca2+ efflux mechanism is probably responsible for maintaining the low internal Ca2+ levels in unstimulated cells."}
{"id": "PMID:9160", "title": "Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle.", "content": "\"Dale's Principle\" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ from typical transmitters by their ability to cross biological barriers; inhibition of decarboxylase in peripheral tissues only (using alpha-methyldopa hydrazine) markedly depletes brain PEA (but not catecholamines). Because of the homeostatic control of the rate of transmitter synthesis and disposition, physiological, pharmacological, and pathological changes may be expected to affect more the tissue levels of related modulators. This modulator theory of drug action is illustrated by the effect of several psychotropic drugs upon the brain levels of PEA and of norepinephrine. For instance, amphetamine initially decreases and then increases brain PEA levels, without altering brain norepinephrine levels. The authors propose an expanded \"Dale's Principle\": each neuron is specific in that it releases at all its endings the same pool of chemical messengers, composed of one transmitter and metabolically related modulators, the relative proportion of which is determined by the physiological state of the cell (biochemical plasticity)...", "contents": "Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle. \"Dale's Principle\" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ from typical transmitters by their ability to cross biological barriers; inhibition of decarboxylase in peripheral tissues only (using alpha-methyldopa hydrazine) markedly depletes brain PEA (but not catecholamines). Because of the homeostatic control of the rate of transmitter synthesis and disposition, physiological, pharmacological, and pathological changes may be expected to affect more the tissue levels of related modulators. This modulator theory of drug action is illustrated by the effect of several psychotropic drugs upon the brain levels of PEA and of norepinephrine. For instance, amphetamine initially decreases and then increases brain PEA levels, without altering brain norepinephrine levels. The authors propose an expanded \"Dale's Principle\": each neuron is specific in that it releases at all its endings the same pool of chemical messengers, composed of one transmitter and metabolically related modulators, the relative proportion of which is determined by the physiological state of the cell (biochemical plasticity)..."}
{"id": "PMID:9162", "title": "Inhibition of bovine renal adenylate cyclase by urinary products.", "content": "The secondary hyperparathyroidism in uremic patients is due to the modification plasma electrolyte concentrations accompanied by a renal resistance to PTH action. We postulate that the retention of a uremic toxin could be at least partly responsible for this resistance. We have tested this hypothesis \"in vitro\" by measuring the action of Middle Molecules on the adenylate cyclase activity stimulated by NaF, PTH and isoproterenol.", "contents": "Inhibition of bovine renal adenylate cyclase by urinary products. The secondary hyperparathyroidism in uremic patients is due to the modification plasma electrolyte concentrations accompanied by a renal resistance to PTH action. We postulate that the retention of a uremic toxin could be at least partly responsible for this resistance. We have tested this hypothesis \"in vitro\" by measuring the action of Middle Molecules on the adenylate cyclase activity stimulated by NaF, PTH and isoproterenol."}
{"id": "PMID:9163", "title": "Sedimentation equilibrium of proteins in density gradients.", "content": "The technique of sedimentation equilibrium in density gradients in the analytical ultracentrifuge has been applied to the study of proteins. A variety of effects and procedures including the use of density marker beads, the effects of pressure on buoyant  density and pH, and the calculation of compositional density gradient proportionality constants and density--refractive index relations have been developed. The buoyant densities of twenty-four proteins have been measured and hydration values computed. The buoyant titrations of six proteins have been measured. These data have been interpreted in terms of the buoyant titrations which have been obtained for six ionizable homopolypeptides, five copolypeptides, two non-ionizable homopolypeptides and three chemically modified proteins. Spectropolarimetry and potentiometric titrations were employed to further interpret these data. Approximate values for dissociation constants, numbers of ionizable residues, and the nature of ions bound or dissociated upon ionization have been obtained. The relation between potentiometric and buoyant titrations and the use of density gradient centrifugation as a probe for protein structure have been explored.", "contents": "Sedimentation equilibrium of proteins in density gradients. The technique of sedimentation equilibrium in density gradients in the analytical ultracentrifuge has been applied to the study of proteins. A variety of effects and procedures including the use of density marker beads, the effects of pressure on buoyant  density and pH, and the calculation of compositional density gradient proportionality constants and density--refractive index relations have been developed. The buoyant densities of twenty-four proteins have been measured and hydration values computed. The buoyant titrations of six proteins have been measured. These data have been interpreted in terms of the buoyant titrations which have been obtained for six ionizable homopolypeptides, five copolypeptides, two non-ionizable homopolypeptides and three chemically modified proteins. Spectropolarimetry and potentiometric titrations were employed to further interpret these data. Approximate values for dissociation constants, numbers of ionizable residues, and the nature of ions bound or dissociated upon ionization have been obtained. The relation between potentiometric and buoyant titrations and the use of density gradient centrifugation as a probe for protein structure have been explored."}
{"id": "PMID:9164", "title": "pH-sensitive glass microelectrodes and intracellular pH measurements.", "content": "1. Some properties of the open-tipped, uninsulated, pH-sensitive glass microelectrode were examined in several electrical experiments. 2. Based on these observations, technical and theoretical problems were considered for application to the pH measurement in small cells. 3. The intracellular pH, (pH)i, of the epithelial cell in rat duodenum measured was approximately 7.0. A reduction in (pH)i was apparent (about 0.3) with the addition of 20 mM-glucose to the bathing fluid. 4. It was concluded that with certain limitations such uninsulated, open-tipped microelectrodes may be successfully utilized for intracellular pH measurements.", "contents": "pH-sensitive glass microelectrodes and intracellular pH measurements. 1. Some properties of the open-tipped, uninsulated, pH-sensitive glass microelectrode were examined in several electrical experiments. 2. Based on these observations, technical and theoretical problems were considered for application to the pH measurement in small cells. 3. The intracellular pH, (pH)i, of the epithelial cell in rat duodenum measured was approximately 7.0. A reduction in (pH)i was apparent (about 0.3) with the addition of 20 mM-glucose to the bathing fluid. 4. It was concluded that with certain limitations such uninsulated, open-tipped microelectrodes may be successfully utilized for intracellular pH measurements."}
{"id": "PMID:9165", "title": "Dynamics of the aromatic amino acid residues in the globular conformation of the basic pancreatic trypsin inhibitor (BPTI). I. 1H NMR studies.", "content": "The basic pancreatic trypsin inhibitor (BPTI) was investigated by high resolution 1H NMR techniques at 360 MHz. Observation of the amide proton resonances of the polypeptide backbone showed that the globular conformation of BPTI determined by X-ray studies in single crystals is maintained in aqueous solution over the temperature range from 4 degrees to 87 degrees. NMR studies over this temperature range of the aromatic amino acid residues of BPTI. i.e. 4 tyrosines and 4 phenylalanines, led to complete assignments of all the aromatic spin systems in the protein. From this, information was obtained on the rotational motions about the C beta--Cv bond axis of the aromatic rings in the globular form of PBTI. At 25 degrees, two tyrosine rings and one phenylalanine ring are rotating rapidly on the NMR time scale. For the other rings the transitions from slow to rapid rotational motions were investigated at variable temperatures and energy barriers for these intramolecular rate processes determined. The studies of the tyrosine resonances had been described in detail in a previous publication. The present paper describes the identification of the phenylalanine resonances and comments on some technical aspects which might be of quite general interest for the analysis of highly resolved 1H NMR spectra of proteins. Data for the tyrosines and the phenylalanines are compiled in three tables, i.e. the pK alpha-values for the tyrosines, the NMR parameters for all eight aromatics, and the parameters delta G not equal to, and, where available, delta H not equal to and delta S not equal to for the rotational motions of the rings.", "contents": "Dynamics of the aromatic amino acid residues in the globular conformation of the basic pancreatic trypsin inhibitor (BPTI). I. 1H NMR studies. The basic pancreatic trypsin inhibitor (BPTI) was investigated by high resolution 1H NMR techniques at 360 MHz. Observation of the amide proton resonances of the polypeptide backbone showed that the globular conformation of BPTI determined by X-ray studies in single crystals is maintained in aqueous solution over the temperature range from 4 degrees to 87 degrees. NMR studies over this temperature range of the aromatic amino acid residues of BPTI. i.e. 4 tyrosines and 4 phenylalanines, led to complete assignments of all the aromatic spin systems in the protein. From this, information was obtained on the rotational motions about the C beta--Cv bond axis of the aromatic rings in the globular form of PBTI. At 25 degrees, two tyrosine rings and one phenylalanine ring are rotating rapidly on the NMR time scale. For the other rings the transitions from slow to rapid rotational motions were investigated at variable temperatures and energy barriers for these intramolecular rate processes determined. The studies of the tyrosine resonances had been described in detail in a previous publication. The present paper describes the identification of the phenylalanine resonances and comments on some technical aspects which might be of quite general interest for the analysis of highly resolved 1H NMR spectra of proteins. Data for the tyrosines and the phenylalanines are compiled in three tables, i.e. the pK alpha-values for the tyrosines, the NMR parameters for all eight aromatics, and the parameters delta G not equal to, and, where available, delta H not equal to and delta S not equal to for the rotational motions of the rings."}
{"id": "PMID:9170", "title": "[Standardization of ADP-induced thrombocyte aggregation].", "content": "It is the purpose of this study to standardize platelet aggregation according to the method of Born. It was found that aggregation is influenced by the time of storage, the pH and temperature of plasma. However, there is no significant correlation between platelet number versus aggregation in healthy subjects. To get reproducible results, the plasma samples should be investigated within 2 hours after venipuncture. During storage temperature of all samples should be constant.", "contents": "[Standardization of ADP-induced thrombocyte aggregation]. It is the purpose of this study to standardize platelet aggregation according to the method of Born. It was found that aggregation is influenced by the time of storage, the pH and temperature of plasma. However, there is no significant correlation between platelet number versus aggregation in healthy subjects. To get reproducible results, the plasma samples should be investigated within 2 hours after venipuncture. During storage temperature of all samples should be constant."}
{"id": "PMID:9173", "title": "A study of the inhalation of pentachlorophenol by rats. Part V. A protein binding study of pentachlorophenol.", "content": "This study examined the effects on PCP binding to BSA by varying the temperature, pH ionic strength, PCP concentration and BSA concentration. It also compared the albumin binding of PCP to the plasma binding of PCP for the rat and human.", "contents": "A study of the inhalation of pentachlorophenol by rats. Part V. A protein binding study of pentachlorophenol. This study examined the effects on PCP binding to BSA by varying the temperature, pH ionic strength, PCP concentration and BSA concentration. It also compared the albumin binding of PCP to the plasma binding of PCP for the rat and human."}
{"id": "PMID:9174", "title": "The effects of pH on the activity of coryneine and related phenolic quaternary ammonium salts on the frog rectus preparation.", "content": "The activity of m-hydroxybenzyltrimethylammonium, coryneine (3:4-dihydroxyphenethyltrimethylammonium, 'quaternary dopamine'), and m-hydroxyphenylpropyltrimethylammonium relative to tetramethylammonium has been measured on the frog rectus preparation (Rana pipiens) at pH 7 and pH 9. 2 The compounds are more active in the more acid environment indicating that ionization of the phenolic group reduces activity to between one-half and one-tenth of that of the form with the intact hydroxyl group. 3 In contrast with the situation at aminoacid receptors, there is no reason to believe that at other receptors zwitterions are likely to be more active than the uncharged forms with which they are in equilibrium.", "contents": "The effects of pH on the activity of coryneine and related phenolic quaternary ammonium salts on the frog rectus preparation. The activity of m-hydroxybenzyltrimethylammonium, coryneine (3:4-dihydroxyphenethyltrimethylammonium, 'quaternary dopamine'), and m-hydroxyphenylpropyltrimethylammonium relative to tetramethylammonium has been measured on the frog rectus preparation (Rana pipiens) at pH 7 and pH 9. 2 The compounds are more active in the more acid environment indicating that ionization of the phenolic group reduces activity to between one-half and one-tenth of that of the form with the intact hydroxyl group. 3 In contrast with the situation at aminoacid receptors, there is no reason to believe that at other receptors zwitterions are likely to be more active than the uncharged forms with which they are in equilibrium."}
{"id": "PMID:9175", "title": "Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability.", "content": "Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups.", "contents": "Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability. Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups."}
{"id": "PMID:9178", "title": "Autolysis of Neisseria gonorrhoeae. Relation between mechanical stability and viability.", "content": "The relationship between the mechanical stability and the viability of N. gonorrhoeae (Type 4) in suspension was investigated. A correlation between viability and optical density recordings was often found. However, in spite of increased mechanical stability in solutions with low pH (5-2) or containing Cu++ or sucrose (10 per cent.), these environments were toxic to the gonococci. A viability preserving effect by Mg++ (4 mM), Ca++ (4 mM), spermine (0-5 mM), polyvinylpyrrolidone (10 per cent.), and low temperature (4 degrees C) was demonstrated. The possibility of improving transport media for gonococci is discussed.", "contents": "Autolysis of Neisseria gonorrhoeae. Relation between mechanical stability and viability. The relationship between the mechanical stability and the viability of N. gonorrhoeae (Type 4) in suspension was investigated. A correlation between viability and optical density recordings was often found. However, in spite of increased mechanical stability in solutions with low pH (5-2) or containing Cu++ or sucrose (10 per cent.), these environments were toxic to the gonococci. A viability preserving effect by Mg++ (4 mM), Ca++ (4 mM), spermine (0-5 mM), polyvinylpyrrolidone (10 per cent.), and low temperature (4 degrees C) was demonstrated. The possibility of improving transport media for gonococci is discussed."}
{"id": "PMID:9181", "title": "Composition of crop and gizzard contents in the laying hen.", "content": "Crop and gizzard contents were analysed at six stages of egg formation. 2. The crop was empty during the day and full during the night while the gizzard contained a constant amount of dry matter. The water content of the crop did not change but that of the gizzard was at a minimum just after the ovulation and at a maximum 18 h later. 3. The osmotic pressure of the gizzard contents remained constant and close to that of the blood; that of the crop contents was almost isotonic at oviposition but hypertonic 18 h later. In both organs the pH of the liquid phase varied cyclicly with the egg formation and was lowest during egg shell deposition. 4. The Na+, K+ and Cl- contents of the crop liquid phase did not vary but Ca2+ increased with decreasing pH.Na+ and K+ were also constant in the gizzard liquid phase but Cl- and Ca2+ increased during shell formation. 5. It is concluded that the amount of HCl secreted by the proventiculus is related to egg shell deposition and that calcium solubilisation depends on microbial fermentation in crop and HCl secretion by proventriculus.", "contents": "Composition of crop and gizzard contents in the laying hen. Crop and gizzard contents were analysed at six stages of egg formation. 2. The crop was empty during the day and full during the night while the gizzard contained a constant amount of dry matter. The water content of the crop did not change but that of the gizzard was at a minimum just after the ovulation and at a maximum 18 h later. 3. The osmotic pressure of the gizzard contents remained constant and close to that of the blood; that of the crop contents was almost isotonic at oviposition but hypertonic 18 h later. In both organs the pH of the liquid phase varied cyclicly with the egg formation and was lowest during egg shell deposition. 4. The Na+, K+ and Cl- contents of the crop liquid phase did not vary but Ca2+ increased with decreasing pH.Na+ and K+ were also constant in the gizzard liquid phase but Cl- and Ca2+ increased during shell formation. 5. It is concluded that the amount of HCl secreted by the proventiculus is related to egg shell deposition and that calcium solubilisation depends on microbial fermentation in crop and HCl secretion by proventriculus."}
{"id": "PMID:9182", "title": "[Guanyl cyclase activities in clonal lines of cultured astroblasts and neuroblasts].", "content": "Guanylate cyclase was found to be present in a number of astroblast and neuroblast clones. No correlations were observed between the enzyme activity and the nature of the clone. The enzyme shows a requirement for manganese ions and is stimulated by calcium. When the astroblast clone NN is cultured together with the neuroblast clone M1 for two months and the astroblast cells again isolated, a reduced guanylate cyclase activity was found.", "contents": "[Guanyl cyclase activities in clonal lines of cultured astroblasts and neuroblasts]. Guanylate cyclase was found to be present in a number of astroblast and neuroblast clones. No correlations were observed between the enzyme activity and the nature of the clone. The enzyme shows a requirement for manganese ions and is stimulated by calcium. When the astroblast clone NN is cultured together with the neuroblast clone M1 for two months and the astroblast cells again isolated, a reduced guanylate cyclase activity was found."}
{"id": "PMID:9183", "title": "[Immunosuppressive role of the liver in the graft versus host reaction].", "content": "The ability of the liver to reduce the intensity of the graft versus host (GVH) reaction has been investigated in F1 hybrid rats implanted with parental lymph nodes. Intrahepatic and intrarenal tissue implantations were compared using classical GVH criteria. The intrahepatic implantation of lymph nodes suppress the mortality observed after intrarenal implantation. The results confirm the interest of portal drainage in organ transplantation and suggest a new site of implantation for lymphoid cells.", "contents": "[Immunosuppressive role of the liver in the graft versus host reaction]. The ability of the liver to reduce the intensity of the graft versus host (GVH) reaction has been investigated in F1 hybrid rats implanted with parental lymph nodes. Intrahepatic and intrarenal tissue implantations were compared using classical GVH criteria. The intrahepatic implantation of lymph nodes suppress the mortality observed after intrarenal implantation. The results confirm the interest of portal drainage in organ transplantation and suggest a new site of implantation for lymphoid cells."}
{"id": "PMID:9184", "title": "[Extraction of LHRH in human urine: study of the extraction of labelled synthetic hormone].", "content": "A method of extraction of synthetic LHRH is studied in human urines, using porous glass (Spherosil) and methanol. In the defined conditions the yield is greeter than 80%. It appears that the method is reproducible. The recovery varies essentially with the quantity of Spherosil and the pH of methanal. The use of methanol acidified at pH 3 increases the speed and the importance of labelled LHRH recovery.", "contents": "[Extraction of LHRH in human urine: study of the extraction of labelled synthetic hormone]. A method of extraction of synthetic LHRH is studied in human urines, using porous glass (Spherosil) and methanol. In the defined conditions the yield is greeter than 80%. It appears that the method is reproducible. The recovery varies essentially with the quantity of Spherosil and the pH of methanal. The use of methanol acidified at pH 3 increases the speed and the importance of labelled LHRH recovery."}
{"id": "PMID:9185", "title": "[Applications of the extraction and of the radioimmunoassay of LH-RH in human urine].", "content": "The existence of endogenous LH RH like immunoreactivity is shown in human urines after appropriate extraction, bu the radioimmunoassay of LH RH. In normaly cycling and menopausal women the quantities of endogenous hormone found in urines are greater after acid extraction than those found after extraction at pH 7. Furthermore, the increase observed by extraction in acidified methanol is directly correlated and proportional to the quantity of hormone assayable by extraction at pH 7. The hypothesis of urinary excretion of LH RH as a polymer of immunoreactive units is suggested by this study.", "contents": "[Applications of the extraction and of the radioimmunoassay of LH-RH in human urine]. The existence of endogenous LH RH like immunoreactivity is shown in human urines after appropriate extraction, bu the radioimmunoassay of LH RH. In normaly cycling and menopausal women the quantities of endogenous hormone found in urines are greater after acid extraction than those found after extraction at pH 7. Furthermore, the increase observed by extraction in acidified methanol is directly correlated and proportional to the quantity of hormone assayable by extraction at pH 7. The hypothesis of urinary excretion of LH RH as a polymer of immunoreactive units is suggested by this study."}
{"id": "PMID:9186", "title": "[Reduction of exercise inudced hyperventilation by blocking beta adrenergic receptors].", "content": "In normal subjects, beta-adrenergic blockage by propranolol or pindolol reduces exercise hyperventilation (40 to 60% VO2 max).", "contents": "[Reduction of exercise inudced hyperventilation by blocking beta adrenergic receptors]. In normal subjects, beta-adrenergic blockage by propranolol or pindolol reduces exercise hyperventilation (40 to 60% VO2 max)."}
{"id": "PMID:9187", "title": "[Splenomegaly reaction of the chick embryo following chorio-allantoid graft of chicken-spleen fragments].", "content": "The spleen enhancement reaction of the chick embryo, following the insertion (grafting or injection procedure) of homologous spleen cells is one of the results of the graft-versus-host reaction (G.V.H. reaction). Irrespective of the usual kinds of G.V.H. reaction measured, it has been proved that the relation between the number of immuno competent cells and the reaction intensity is linear. Our study shows that the relation is not the same when the chorio-allantois membrane grafting procedure is used instead of injection into the veins. However, two facts remain unchanged 1) the minimal amount of spleen cells sufficient to provoke a spleen enhancement is low, 2) there is a link between the number of homologous spleen cells and the rate of spleen enhancement, but in this case it was not shown to be linear. In the light of this, the role played by the chorio-allantois membrane is being debated.", "contents": "[Splenomegaly reaction of the chick embryo following chorio-allantoid graft of chicken-spleen fragments]. The spleen enhancement reaction of the chick embryo, following the insertion (grafting or injection procedure) of homologous spleen cells is one of the results of the graft-versus-host reaction (G.V.H. reaction). Irrespective of the usual kinds of G.V.H. reaction measured, it has been proved that the relation between the number of immuno competent cells and the reaction intensity is linear. Our study shows that the relation is not the same when the chorio-allantois membrane grafting procedure is used instead of injection into the veins. However, two facts remain unchanged 1) the minimal amount of spleen cells sufficient to provoke a spleen enhancement is low, 2) there is a link between the number of homologous spleen cells and the rate of spleen enhancement, but in this case it was not shown to be linear. In the light of this, the role played by the chorio-allantois membrane is being debated."}
{"id": "PMID:9188", "title": "[Influence of metabolic alkalosis on adrenaline hyperglycemia of the dog].", "content": "The metabolic alkalosis, induced by the administration bicarbonate, reduces adrenaline hyperglycemia in fasted dog.", "contents": "[Influence of metabolic alkalosis on adrenaline hyperglycemia of the dog]. The metabolic alkalosis, induced by the administration bicarbonate, reduces adrenaline hyperglycemia in fasted dog."}
{"id": "PMID:9189", "title": "Purification and characterization of tonin.", "content": "Tonin was purified from rat submaxillary glands by differential centrifugation, ammonium sulphate precipitation, gel filtration on Sephadex G150, and by ion-exchange chromatography on DEAE-cellulose, phospho-cellulose, SP-Sephadex C25, and SP-Sephadex C50. Purified tonin was shown to be homogeneous by analytical electrophoresis and by analytical ultracentrifugation analysis. Purified tonin was very stable when stored in buffers of low pH values or when incubated at high temperatures in neutral solution. The molecular weight estimated by sedimentation equilibrium was 28 700. The pH optimum was near 6.8 in a 0.1 M potassium phosphate buffer. The Michaelis-Menten constant for tonin using angiotensin I as substrate was about 4 X 10(-5) M. Tonin activity was strongly inhibited by plasma. Kinetic studies using angiotensin I as substrate showed that the inhibition of tonin by plasma was of the non-competitive type.", "contents": "Purification and characterization of tonin. Tonin was purified from rat submaxillary glands by differential centrifugation, ammonium sulphate precipitation, gel filtration on Sephadex G150, and by ion-exchange chromatography on DEAE-cellulose, phospho-cellulose, SP-Sephadex C25, and SP-Sephadex C50. Purified tonin was shown to be homogeneous by analytical electrophoresis and by analytical ultracentrifugation analysis. Purified tonin was very stable when stored in buffers of low pH values or when incubated at high temperatures in neutral solution. The molecular weight estimated by sedimentation equilibrium was 28 700. The pH optimum was near 6.8 in a 0.1 M potassium phosphate buffer. The Michaelis-Menten constant for tonin using angiotensin I as substrate was about 4 X 10(-5) M. Tonin activity was strongly inhibited by plasma. Kinetic studies using angiotensin I as substrate showed that the inhibition of tonin by plasma was of the non-competitive type."}
{"id": "PMID:9191", "title": "A particulate chitin synthase from Aspergillus flavus Link: the properties, location, and levels of activity in mycelium and regenerating protoplast preparations.", "content": "Chitin synthase (ED 2.4.1.16) has been characterized in Aspergillus flavus. A K(m) value of 2.5 m(M) was obtained for the substrate UDPGlcNAc. The enzyme had a requirement for GlcNAc, and Mg2+ and activity was increased in the presence of soluble chitodextrins F1 and F2. The optimum activity was obtained using Tris--HCl buffer, pH 7.5, with a secondary peak at pH 6.2 and an incubation temperature of 29.5 degrees C. Distribution patterns of chitin synthase in protoplasts and mycelial material were very similar. The highest specific activity was found in a 200 000 X g fraction. Enzyme levels in growing mycelium increased during the exponential growth phase after which they declined. Activity also increased during the early stages of regeneration of both conidial and mycelial protoplasts, despite an initial lack in net protein synthesis. Chitin synthase levels were also dependent upon the carbon source available during regeneration.", "contents": "A particulate chitin synthase from Aspergillus flavus Link: the properties, location, and levels of activity in mycelium and regenerating protoplast preparations. Chitin synthase (ED 2.4.1.16) has been characterized in Aspergillus flavus. A K(m) value of 2.5 m(M) was obtained for the substrate UDPGlcNAc. The enzyme had a requirement for GlcNAc, and Mg2+ and activity was increased in the presence of soluble chitodextrins F1 and F2. The optimum activity was obtained using Tris--HCl buffer, pH 7.5, with a secondary peak at pH 6.2 and an incubation temperature of 29.5 degrees C. Distribution patterns of chitin synthase in protoplasts and mycelial material were very similar. The highest specific activity was found in a 200 000 X g fraction. Enzyme levels in growing mycelium increased during the exponential growth phase after which they declined. Activity also increased during the early stages of regeneration of both conidial and mycelial protoplasts, despite an initial lack in net protein synthesis. Chitin synthase levels were also dependent upon the carbon source available during regeneration."}
{"id": "PMID:9192", "title": "Stable L-forms of Clostridium perfringens and their growth on glass surfaces.", "content": "L-forms of Clostridium perfringens were induced in brain heart infusion broth containing 10% sucrose and 2 units of penicillin. After a few hours of growth, spheroplasts, granules, and elongated bacilli were apparent. At 24-h intervals, serial subcultures were made in the above medium which resulted in a culture composed entirely of spheroplasts (or protoplasts) and granules. Upon the withdrawal of penicillin these L-form cultures grew well and, after 100 passages, there was no reversion to the bacillary form. Sucrose could also be withdrawn from the medium. The effects of centrifugation, osmotic stabilizer, ultraviolet light, temperature, pH, and lyophilization upon stable L-forms were examined. L-forms were found to attach to the walls of culture tubes during trowth and sheets of L-form growth were obtained on cover slips in Leighton tubes and on the sides of medicine bottles.", "contents": "Stable L-forms of Clostridium perfringens and their growth on glass surfaces. L-forms of Clostridium perfringens were induced in brain heart infusion broth containing 10% sucrose and 2 units of penicillin. After a few hours of growth, spheroplasts, granules, and elongated bacilli were apparent. At 24-h intervals, serial subcultures were made in the above medium which resulted in a culture composed entirely of spheroplasts (or protoplasts) and granules. Upon the withdrawal of penicillin these L-form cultures grew well and, after 100 passages, there was no reversion to the bacillary form. Sucrose could also be withdrawn from the medium. The effects of centrifugation, osmotic stabilizer, ultraviolet light, temperature, pH, and lyophilization upon stable L-forms were examined. L-forms were found to attach to the walls of culture tubes during trowth and sheets of L-form growth were obtained on cover slips in Leighton tubes and on the sides of medicine bottles."}
{"id": "PMID:9193", "title": "Competition between Phytophthora cinnamomi and Trichoderma spp. in autoclaved soil.", "content": "Results from analyses of beta-glucosidase (EC 3.2.1.21) and phosphatase (EC 3.1.3.1;EC 3.1.3.2) activities indicated that presence of a Trichoderma isolate reduced development of Phytophthora cinnamomi. It was also observed that P. cinnamomi was more competitive in coinoculated cultures than in cultures where Trichoderma was added on day 3. Analysis of trehalase (EC 3.2.1.28) activity indicated that Trichoderma either utilized portions of the P. cinnamomi mycelium as substrate or the action of P. cinnamomi released additional nutrients not normally available to Trichoderma. Ther stronger Trichoderma isolate was T. harzianum.", "contents": "Competition between Phytophthora cinnamomi and Trichoderma spp. in autoclaved soil. Results from analyses of beta-glucosidase (EC 3.2.1.21) and phosphatase (EC 3.1.3.1;EC 3.1.3.2) activities indicated that presence of a Trichoderma isolate reduced development of Phytophthora cinnamomi. It was also observed that P. cinnamomi was more competitive in coinoculated cultures than in cultures where Trichoderma was added on day 3. Analysis of trehalase (EC 3.2.1.28) activity indicated that Trichoderma either utilized portions of the P. cinnamomi mycelium as substrate or the action of P. cinnamomi released additional nutrients not normally available to Trichoderma. Ther stronger Trichoderma isolate was T. harzianum."}
{"id": "PMID:9194", "title": "Antifungal properties of alpha,omega-alkanedicarboxylic acids and their dimethyl esters.", "content": "Thirteen alpha, omega-alkanedicarboxylic acids (C2-C12, C14, and C16) and their dimethyl esters were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabourauc dextrose agar at pH 4.0 AND 5.6. Toxicity to Canadida albicans, Trichophyton mentagrophytes, and Mucor mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The dicarboxylic acids possessed very poor to no antifungal activity against all six fungi. The fungitoxicity of the dimethyl esters to A. niger, T. viride, and M. verrucaria was C8 = C9 greater than C7 greater than C6 = C5 greater than C10 greater than C4 greater than C11 and to C. albicans, T. mentagrophytes, and M. mucedo C9 greater than C10 greater than C11 greater than C12 = C8 greater than C7 greater than C6 greater than C5 greater than C4 greater than C3. The fungitoxicity of the esters of fatty acids and alpha-omega-alkanedicarboxylic acids was influenced by chain length and not by the pH of the medium or the absence or presence of beef serum.", "contents": "Antifungal properties of alpha,omega-alkanedicarboxylic acids and their dimethyl esters. Thirteen alpha, omega-alkanedicarboxylic acids (C2-C12, C14, and C16) and their dimethyl esters were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabourauc dextrose agar at pH 4.0 AND 5.6. Toxicity to Canadida albicans, Trichophyton mentagrophytes, and Mucor mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The dicarboxylic acids possessed very poor to no antifungal activity against all six fungi. The fungitoxicity of the dimethyl esters to A. niger, T. viride, and M. verrucaria was C8 = C9 greater than C7 greater than C6 = C5 greater than C10 greater than C4 greater than C11 and to C. albicans, T. mentagrophytes, and M. mucedo C9 greater than C10 greater than C11 greater than C12 = C8 greater than C7 greater than C6 greater than C5 greater than C4 greater than C3. The fungitoxicity of the esters of fatty acids and alpha-omega-alkanedicarboxylic acids was influenced by chain length and not by the pH of the medium or the absence or presence of beef serum."}
{"id": "PMID:9197", "title": "Tryptophanyl and carboxylic acid residues in the active centre of glucoamylase I from Aspergillus niger.", "content": "The pH-dependence of the photo-oxidation of L-tryptophan, in the presence of Rose Bengal and Methylene Blue, has been investigated. True, initial rate constants were determined in order to circumvent errors due to secondary processes. Photo-oxidation of glycoamylase I from A. niger in the presence of Methylene Blue or Rose Bengal resulted in a pH-dependent loss of enzymic activity, which was analogous to the destruction of free L-tryptophan during photo-oxidation. The loss of enzymic activity was closely associated with the destruction of tryptophan residues in the enzyme. Significant protection of both enzymic activity and tryptophanyl residues in the enzyme molecule was achieved by performing the photo-oxidation in the presence of maltose, which is a substrate for the enzyme. The tryptophanyl residues of glucoamylase I, which had been inactivated by reaction of its carboxylic acid residues with glycine methyl ester in the presence of a water-soluble carbodi-imide, were also substantially protected by maltose. It is concluded that the active centre of glucoamylase I is a cleft lined with tryptophanyl residues that participate in the binding of the substrate. One or more carboxylic acid residues are involved in bond cleavage.", "contents": "Tryptophanyl and carboxylic acid residues in the active centre of glucoamylase I from Aspergillus niger. The pH-dependence of the photo-oxidation of L-tryptophan, in the presence of Rose Bengal and Methylene Blue, has been investigated. True, initial rate constants were determined in order to circumvent errors due to secondary processes. Photo-oxidation of glycoamylase I from A. niger in the presence of Methylene Blue or Rose Bengal resulted in a pH-dependent loss of enzymic activity, which was analogous to the destruction of free L-tryptophan during photo-oxidation. The loss of enzymic activity was closely associated with the destruction of tryptophan residues in the enzyme. Significant protection of both enzymic activity and tryptophanyl residues in the enzyme molecule was achieved by performing the photo-oxidation in the presence of maltose, which is a substrate for the enzyme. The tryptophanyl residues of glucoamylase I, which had been inactivated by reaction of its carboxylic acid residues with glycine methyl ester in the presence of a water-soluble carbodi-imide, were also substantially protected by maltose. It is concluded that the active centre of glucoamylase I is a cleft lined with tryptophanyl residues that participate in the binding of the substrate. One or more carboxylic acid residues are involved in bond cleavage."}
{"id": "PMID:9198", "title": "Production and purification of two hemicellulases from Cephalosporium sacchari.", "content": "The production of extracellular hemicellulases by the fungus Cephalosporium sacchari was studied in the presence of various sources of carbon and at various initial pH values and temperatures. Hemicellulose B and holocellulose from spear grass (Heteropogon contortus) were the best sources of carbon, and the optimum temperature was 27 degrees. The initial pH value had little influence on the final yield of hemicellulases. Two hemicellulases (HC-III and HC-IV) were purified by ammonium sulphate precipitation and isoelectric focusing. Their molecular weights were 10,700 and 9,550, and their pI values 9.40 and 6.0, respectively. HC-III hydrolysed hemicellulose B to oligosaccharides without production of monosaccharides.", "contents": "Production and purification of two hemicellulases from Cephalosporium sacchari. The production of extracellular hemicellulases by the fungus Cephalosporium sacchari was studied in the presence of various sources of carbon and at various initial pH values and temperatures. Hemicellulose B and holocellulose from spear grass (Heteropogon contortus) were the best sources of carbon, and the optimum temperature was 27 degrees. The initial pH value had little influence on the final yield of hemicellulases. Two hemicellulases (HC-III and HC-IV) were purified by ammonium sulphate precipitation and isoelectric focusing. Their molecular weights were 10,700 and 9,550, and their pI values 9.40 and 6.0, respectively. HC-III hydrolysed hemicellulose B to oligosaccharides without production of monosaccharides."}
{"id": "PMID:9199", "title": "Bromine oxidation of methyl alpha- and beta-pyranosides of D-galactose, D-glucose, and D-mannose.", "content": "Methyl alpha- and beta-pyranosides of D-galactose, D-glucose, and D-mannose have been oxidized with bromine in aqueous solution at various pH values. The resulting keto glycosides were converted into their more-stable O-methyloxime derivatives which were characterized by spectroscopy and chromatography. Oxidation at a ring carbon atom where the hydrogen is axial is hindered by bulky substituents in syn (i.e., a 1,3) diaxial relationship. Thus, the aglycon group in the alpha anomers protects position 3, the axial HO-4 in galactopyranosides protects position 2, and the axial HO-2 in mannopyranosides protects position 4 from oxidation.", "contents": "Bromine oxidation of methyl alpha- and beta-pyranosides of D-galactose, D-glucose, and D-mannose. Methyl alpha- and beta-pyranosides of D-galactose, D-glucose, and D-mannose have been oxidized with bromine in aqueous solution at various pH values. The resulting keto glycosides were converted into their more-stable O-methyloxime derivatives which were characterized by spectroscopy and chromatography. Oxidation at a ring carbon atom where the hydrogen is axial is hindered by bulky substituents in syn (i.e., a 1,3) diaxial relationship. Thus, the aglycon group in the alpha anomers protects position 3, the axial HO-4 in galactopyranosides protects position 2, and the axial HO-2 in mannopyranosides protects position 4 from oxidation."}
{"id": "PMID:9200", "title": "Multiple forms of DNA-dependent DNA polymerase during early development and in somatic cells of Xenopus laevis.", "content": "Four distinct DNA-dependent DNA polymerase activities (DNA polymerases I, II, III and IV according to the order of elution from a DEAE column) have been separated from extracts of unfertilized Xenopus laevis eggs. The same activities, on the basis of their chromatographic properties, template specificities and sedimentation coefficients, have been found in embryos at least until the gastrula stage. On the other hand, Xenopus kidney cells grown in culture, as well as full grown oocytes lack DNA polymerase I. These data suggest the DNA polymerase I might be a special DNA polymerase activity involved in the extremely rapid DNA synthesis which takes place during early development of X. laevis.", "contents": "Multiple forms of DNA-dependent DNA polymerase during early development and in somatic cells of Xenopus laevis. Four distinct DNA-dependent DNA polymerase activities (DNA polymerases I, II, III and IV according to the order of elution from a DEAE column) have been separated from extracts of unfertilized Xenopus laevis eggs. The same activities, on the basis of their chromatographic properties, template specificities and sedimentation coefficients, have been found in embryos at least until the gastrula stage. On the other hand, Xenopus kidney cells grown in culture, as well as full grown oocytes lack DNA polymerase I. These data suggest the DNA polymerase I might be a special DNA polymerase activity involved in the extremely rapid DNA synthesis which takes place during early development of X. laevis."}
{"id": "PMID:9204", "title": "[Ionic control of biochemical reactions].", "content": "It is shown that pH and ionic strength are tightly interdependent in cytochrome oxidase activity at the level of inner membranes of the mitochondrion, as a direct consequence of the polyanionic environment of this enzyme. Application of polyelectrolyte theory explains a number of biochemical reactions controlled by ionic strength fluctuations.", "contents": "[Ionic control of biochemical reactions]. It is shown that pH and ionic strength are tightly interdependent in cytochrome oxidase activity at the level of inner membranes of the mitochondrion, as a direct consequence of the polyanionic environment of this enzyme. Application of polyelectrolyte theory explains a number of biochemical reactions controlled by ionic strength fluctuations."}
{"id": "PMID:9208", "title": "Oxidation of lactate by human serum.", "content": "The oxidation of lactate by lactate dehydrogenase of human serum is described, and the kinetics of the reaction are examined. It seems that at higher pH values which are optimal for the faster moving isoenzymes of lactate dehydrogenase, slower moving entities show only a part of their activity. In contrast, M type isoenzymes are active at lower pH values, where H type entities are partly inactivated.", "contents": "Oxidation of lactate by human serum. The oxidation of lactate by lactate dehydrogenase of human serum is described, and the kinetics of the reaction are examined. It seems that at higher pH values which are optimal for the faster moving isoenzymes of lactate dehydrogenase, slower moving entities show only a part of their activity. In contrast, M type isoenzymes are active at lower pH values, where H type entities are partly inactivated."}
{"id": "PMID:9209", "title": "Isoelectric focusing of spectrin components in hereditary spherocytosis.", "content": "1. By isoelectric focusing in 8 M urea, spectrin purified from normal human erythrocytes was resolved into 12 to 15 peptide bands differing by their isoelectric point. Most of them were focused between pH 6.4 and 5.2, one at pH 8.7 and some minor components between pH 7.4 and 6.8. 2. The results were not influenced by the erythrocyte population age. 3. Spectrin purified from erythrocytes of five patients with hereditary spherocytosis gave similar isoelectric focusing patterns, with the exception of the lack of the pH 8.7-focused component in two related patients.", "contents": "Isoelectric focusing of spectrin components in hereditary spherocytosis. 1. By isoelectric focusing in 8 M urea, spectrin purified from normal human erythrocytes was resolved into 12 to 15 peptide bands differing by their isoelectric point. Most of them were focused between pH 6.4 and 5.2, one at pH 8.7 and some minor components between pH 7.4 and 6.8. 2. The results were not influenced by the erythrocyte population age. 3. Spectrin purified from erythrocytes of five patients with hereditary spherocytosis gave similar isoelectric focusing patterns, with the exception of the lack of the pH 8.7-focused component in two related patients."}
{"id": "PMID:9210", "title": "Isolation and characterization of isoenzymes of human salivary and pancreatic alpha-amylase.", "content": "Human salivary and pancreatic alpha-amylase (1,4-glucan 4-glucanohydrolase, EC 3.2.1.1) were separated by electrofocusing. In the first case we obtained six isoenzymes with isoelectric points of pH 5.70, 5.72, 6.23, 6.32, 6.73 and 6.88. Human pancreatic alpha-amylase has been separated into eight isoenzymes with isoelectric points of pH 5.72, 5.77, 5.88, 6.05, 6.23, 6.69, 6.72 and 6.95. Some of the isoenzymes were shown to be sialoproteins; others representing about 80% of the total activity did not contain neuraminic acid. The molecular weight of the non-sialoproteinic isoenzymes was found to be about 47 000 in all cases.", "contents": "Isolation and characterization of isoenzymes of human salivary and pancreatic alpha-amylase. Human salivary and pancreatic alpha-amylase (1,4-glucan 4-glucanohydrolase, EC 3.2.1.1) were separated by electrofocusing. In the first case we obtained six isoenzymes with isoelectric points of pH 5.70, 5.72, 6.23, 6.32, 6.73 and 6.88. Human pancreatic alpha-amylase has been separated into eight isoenzymes with isoelectric points of pH 5.72, 5.77, 5.88, 6.05, 6.23, 6.69, 6.72 and 6.95. Some of the isoenzymes were shown to be sialoproteins; others representing about 80% of the total activity did not contain neuraminic acid. The molecular weight of the non-sialoproteinic isoenzymes was found to be about 47 000 in all cases."}
{"id": "PMID:9211", "title": "Determination of serum urea by mass fragmentography.", "content": "A mass fragmentographic method of high accuracy for determination of serum urea is described. A fixed amount of [15N2]urea is added to a fixed amount of serum, then the urea is converted into 5,5-diallyl barbituric acid by coupling with diallyl malonic acid diethyl ester. The barbiturate is then transferred from an alkaline water phase into an organic phase containing methyl iodine by ion-pair extraction using tetrabutyl ammonium as the positive counterion. The amount of urea is determined from the ratio between the recordings at m/e 236 and m/e 238 obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with an MID-unit (multiple-ion detector). The two ions used correspond to the molecular peak in the mass spectrum of the methyl derivative of unlabeled and labeled 5,5-diallyl barbituric acid, respectively. The relative standard deviation of the method was 3.6%. A comparison between the mass fragmentographic method and a routine method for determination of serum urea based on the urease-Berthelot reaction gave a high correlation (r = 0.99) and a regression coefficient of 0.95.", "contents": "Determination of serum urea by mass fragmentography. A mass fragmentographic method of high accuracy for determination of serum urea is described. A fixed amount of [15N2]urea is added to a fixed amount of serum, then the urea is converted into 5,5-diallyl barbituric acid by coupling with diallyl malonic acid diethyl ester. The barbiturate is then transferred from an alkaline water phase into an organic phase containing methyl iodine by ion-pair extraction using tetrabutyl ammonium as the positive counterion. The amount of urea is determined from the ratio between the recordings at m/e 236 and m/e 238 obtained after analysis with a combined gas chromatograph-mass spectrometer equipped with an MID-unit (multiple-ion detector). The two ions used correspond to the molecular peak in the mass spectrum of the methyl derivative of unlabeled and labeled 5,5-diallyl barbituric acid, respectively. The relative standard deviation of the method was 3.6%. A comparison between the mass fragmentographic method and a routine method for determination of serum urea based on the urease-Berthelot reaction gave a high correlation (r = 0.99) and a regression coefficient of 0.95."}
{"id": "PMID:9212", "title": "Modification of neonatal screening test for erythrocyte glucose-6-phosphate dehydrogenase deficiency.", "content": "An improved technique is proposed for detecting G6PD deficiency on dried blood. A simple and rapid ascending chromatography of NADPH makes it possible to differentiate the false positives, too frequently found with Beutler's spot test (1968).", "contents": "Modification of neonatal screening test for erythrocyte glucose-6-phosphate dehydrogenase deficiency. An improved technique is proposed for detecting G6PD deficiency on dried blood. A simple and rapid ascending chromatography of NADPH makes it possible to differentiate the false positives, too frequently found with Beutler's spot test (1968)."}
{"id": "PMID:9213", "title": "Lysyl oxidase activity in human normal skins and postburn scars.", "content": "Lysyl oxidase activity of human normal skins derived from the frontal thighs of 33 subjects showed large variations and the mean value was 11 455 +/- 7 172 (S.D.) cpm/g of wet weight tissue. The age of lesion affected the lysyl oxidase activity in postburn scars. Granulation tissues showed a fairly low activity; however, the activity increased sharply within 2--3 months, and reached a significantly higher value than that of normal skin. The high level of activity continued for up to 2--3 years, then gradually decreased to normal range after 5 years or so. Lysyl oxidase activity was detected only after 4 M urea treatment of tissues. Benzylamine oxidase activity also showed large variations in both normal skins and postburn scars, with mean values of: 0.128 +/- 0.077 (S.D.) and 0.145 +/- 0.090 (S.D.) mmol/g of wet weight/h, respectively. No correlation was observed between lysyl oxidase and benzylamine oxidase activities. The granulation tissues showed significantly high values of benzylamine oxidase activity in contrast to the low values of lysyl oxidase activity.", "contents": "Lysyl oxidase activity in human normal skins and postburn scars. Lysyl oxidase activity of human normal skins derived from the frontal thighs of 33 subjects showed large variations and the mean value was 11 455 +/- 7 172 (S.D.) cpm/g of wet weight tissue. The age of lesion affected the lysyl oxidase activity in postburn scars. Granulation tissues showed a fairly low activity; however, the activity increased sharply within 2--3 months, and reached a significantly higher value than that of normal skin. The high level of activity continued for up to 2--3 years, then gradually decreased to normal range after 5 years or so. Lysyl oxidase activity was detected only after 4 M urea treatment of tissues. Benzylamine oxidase activity also showed large variations in both normal skins and postburn scars, with mean values of: 0.128 +/- 0.077 (S.D.) and 0.145 +/- 0.090 (S.D.) mmol/g of wet weight/h, respectively. No correlation was observed between lysyl oxidase and benzylamine oxidase activities. The granulation tissues showed significantly high values of benzylamine oxidase activity in contrast to the low values of lysyl oxidase activity."}
{"id": "PMID:9214", "title": "Sensitive radiochemical esterolytic assays for urokinase.", "content": "Two radiochemical esterolytic assays for urokinase are described. One assay is based on the urokinase-dependent hydrolysis of Nalpha-acetyl-glycyl-L-lysine [3H]methyl ester and the other on the urokinase-dependent activation of plasminogen and assay of generated plasmin with Nalpha-tosyl-L-arginine [3H]methyl ester. The assays are performed in tubes placed in liquid scintillation counting vials. At the end of the experiment generated [3H]methanol is extracted into the liquid scintillation cocktail and counted. Unhydrolyzed substrate largely remains in the aqueous phase and contributes only a small fraction of the counts. This facile separation of 3H-labeled alcohol from the ester substrate allows the simple and highly sensitive assay for urokinase. The assays give results in good agreement with the classical fibrin plate assay.", "contents": "Sensitive radiochemical esterolytic assays for urokinase. Two radiochemical esterolytic assays for urokinase are described. One assay is based on the urokinase-dependent hydrolysis of Nalpha-acetyl-glycyl-L-lysine [3H]methyl ester and the other on the urokinase-dependent activation of plasminogen and assay of generated plasmin with Nalpha-tosyl-L-arginine [3H]methyl ester. The assays are performed in tubes placed in liquid scintillation counting vials. At the end of the experiment generated [3H]methanol is extracted into the liquid scintillation cocktail and counted. Unhydrolyzed substrate largely remains in the aqueous phase and contributes only a small fraction of the counts. This facile separation of 3H-labeled alcohol from the ester substrate allows the simple and highly sensitive assay for urokinase. The assays give results in good agreement with the classical fibrin plate assay."}
{"id": "PMID:9215", "title": "Titration of human placental alkaline phosphatase with radioactive orthophosphate.", "content": "Human placental alkaline phosphatase incorporates radioactive phosphate specifically and covalently at acid pH. By titration of solutions of the purified enzyme with radioactive orthophosphate, the enzyme was shown to incorporate up to 2 phosphate groups per molecule. No evidence was found to suggest that the two sites had different affinities for phosphate. Similar titrations can be used to determine the molarity of solutions of non-placental alkaline phosphatases of unknown purity, if these also are assumed to possess 2 binding sites per molecule.", "contents": "Titration of human placental alkaline phosphatase with radioactive orthophosphate. Human placental alkaline phosphatase incorporates radioactive phosphate specifically and covalently at acid pH. By titration of solutions of the purified enzyme with radioactive orthophosphate, the enzyme was shown to incorporate up to 2 phosphate groups per molecule. No evidence was found to suggest that the two sites had different affinities for phosphate. Similar titrations can be used to determine the molarity of solutions of non-placental alkaline phosphatases of unknown purity, if these also are assumed to possess 2 binding sites per molecule."}
{"id": "PMID:9216", "title": "Degradation of arylsulfate by hepatic microsomes.", "content": "The enzyme liberated by some treatments and the changes in arylsulfatase C activity in chronic hepatic damage were investigated in rat liver. 1. The enzyme activity liberated by ultrasound was the highest in the conditions studied. 2. Arylsulfatase C was assayed using p-nitrophenyl sulfate in 0.25 M Tris/acetate buffer as substrate. It is shown that this method can be used to measure arylsulfatase C activity in a mixture of arylsulfatases A and B. 3. The enzyme is mainly located in the microsomal fraction in rat liver. In toxic hepatic damage, the enzyme activity decreases from the early stage; decreasing markedly in chronic hepatic damage. The activity seems to reflect damage to the microsomes and therefore arylsulfatase C activity can be a good indicator of injury to liver microsomes.", "contents": "Degradation of arylsulfate by hepatic microsomes. The enzyme liberated by some treatments and the changes in arylsulfatase C activity in chronic hepatic damage were investigated in rat liver. 1. The enzyme activity liberated by ultrasound was the highest in the conditions studied. 2. Arylsulfatase C was assayed using p-nitrophenyl sulfate in 0.25 M Tris/acetate buffer as substrate. It is shown that this method can be used to measure arylsulfatase C activity in a mixture of arylsulfatases A and B. 3. The enzyme is mainly located in the microsomal fraction in rat liver. In toxic hepatic damage, the enzyme activity decreases from the early stage; decreasing markedly in chronic hepatic damage. The activity seems to reflect damage to the microsomes and therefore arylsulfatase C activity can be a good indicator of injury to liver microsomes."}
{"id": "PMID:9217", "title": "Ultramicromethod for the determination of human arginase in the presence of urea.", "content": "A technique for arginase determination in body fluids in the presence of urea is described. [14C]Arginine is hydrolysed by arginase to [14C]urea and ornithine. [14C]Urea is separated with paper chromatography and measured in a liquid scintillation counter. The experimental conditions including the pH, substrate concentration, activator, solvent for chromatography, urea inhibition, and arginase in hemolysates, are discussed.", "contents": "Ultramicromethod for the determination of human arginase in the presence of urea. A technique for arginase determination in body fluids in the presence of urea is described. [14C]Arginine is hydrolysed by arginase to [14C]urea and ornithine. [14C]Urea is separated with paper chromatography and measured in a liquid scintillation counter. The experimental conditions including the pH, substrate concentration, activator, solvent for chromatography, urea inhibition, and arginase in hemolysates, are discussed."}
{"id": "PMID:9218", "title": "Increased serum gamma-glutamyltransferase in hypertriglyceridemia: comparison with serum pseudocholinesterase.", "content": "Both gamma-glutamyltransferase (gammaGT) and pseudocholinesterase (PCE) were found to be increased in hypertriglyceridemic subjects. High values of gammaGT were noted in alcoholic subjects and especially in those with either increased serum triglyceride or alanine aminotransferase higher than 16 mU/ml, while PCE was not significantly changed in alcoholic subjects. Although both enzymes were strongly correlated with the logarithm of serum triglyceride and the prebeta electrophoretic fraction, there were striking differences concerning their behavior in various hypertriglyceridemic subjects. PCE activity was high even in moderate hypertriglyceridemias but its correlation with serum triglyceride had a tendency to flatten with increasing concentration of triglyceride. However, increase of gammaGT was rather characteristic for gross hypetriglyceridemia. Short-term, triglyceride-lowering therapy was accompanied by a tendency to normalization of gammaGT, while PCE values were not influenced. An attempt was made to interpret these changes of serum-enzyme activity in hypertriglyceridemia in connection with mechanisms of lipoprotein synthesis and with the pathogeny of hyperlipemic conditions.", "contents": "Increased serum gamma-glutamyltransferase in hypertriglyceridemia: comparison with serum pseudocholinesterase. Both gamma-glutamyltransferase (gammaGT) and pseudocholinesterase (PCE) were found to be increased in hypertriglyceridemic subjects. High values of gammaGT were noted in alcoholic subjects and especially in those with either increased serum triglyceride or alanine aminotransferase higher than 16 mU/ml, while PCE was not significantly changed in alcoholic subjects. Although both enzymes were strongly correlated with the logarithm of serum triglyceride and the prebeta electrophoretic fraction, there were striking differences concerning their behavior in various hypertriglyceridemic subjects. PCE activity was high even in moderate hypertriglyceridemias but its correlation with serum triglyceride had a tendency to flatten with increasing concentration of triglyceride. However, increase of gammaGT was rather characteristic for gross hypetriglyceridemia. Short-term, triglyceride-lowering therapy was accompanied by a tendency to normalization of gammaGT, while PCE values were not influenced. An attempt was made to interpret these changes of serum-enzyme activity in hypertriglyceridemia in connection with mechanisms of lipoprotein synthesis and with the pathogeny of hyperlipemic conditions."}
{"id": "PMID:9219", "title": "Circulating tissue antigens. III. Identification and characterization of antigens of limited and of wide body is distribution in human gall bladder bile. Presence in serum of patients with acute hepatitis.", "content": "Three antigens shared by bile and tissues (BT-1, BT-2 and BT-3) and one shared by bile and saliva (BA) were identified in human gallbladder bile by immunodiffusion. The former were detected in all bile specimens examined, whereas the latter was detected only in half. BT-1 was limited in distribution to kidney, urine and bile; whereas BT-2 and BT-3 were widely distributed mainly in liver, lung and bile. The antigens were not present in biles of other mammals tested, with the exception of BA which was also present in Rhesus monkey. All antigens were inactivated by Pronase, had relative electrophoretic mobilities of serum globulins and separated from each other in Sephadex G-200 gel filtration and ammonium sulphate fractionation. Ethanol inactivated BT-1 and precipitated the other antigens. BT-2 and BA were relatively resistant to boiling temperature and acid pH, whereas BT-1 and BT-3 were susceptible. Antigens BT-2 and BT-3 were detected in serum of patients with acute hepatitis but not of patients with other diseases or of normal controls.", "contents": "Circulating tissue antigens. III. Identification and characterization of antigens of limited and of wide body is distribution in human gall bladder bile. Presence in serum of patients with acute hepatitis. Three antigens shared by bile and tissues (BT-1, BT-2 and BT-3) and one shared by bile and saliva (BA) were identified in human gallbladder bile by immunodiffusion. The former were detected in all bile specimens examined, whereas the latter was detected only in half. BT-1 was limited in distribution to kidney, urine and bile; whereas BT-2 and BT-3 were widely distributed mainly in liver, lung and bile. The antigens were not present in biles of other mammals tested, with the exception of BA which was also present in Rhesus monkey. All antigens were inactivated by Pronase, had relative electrophoretic mobilities of serum globulins and separated from each other in Sephadex G-200 gel filtration and ammonium sulphate fractionation. Ethanol inactivated BT-1 and precipitated the other antigens. BT-2 and BA were relatively resistant to boiling temperature and acid pH, whereas BT-1 and BT-3 were susceptible. Antigens BT-2 and BT-3 were detected in serum of patients with acute hepatitis but not of patients with other diseases or of normal controls."}
{"id": "PMID:9221", "title": "Generation of ammonia from non-urea sources in a faecal incubation system.", "content": "1. A 25% faecal suspension in sodium chloride solution, incubated anaerobically at 37 degrees C for 48 h, showed excellent survival of all the main groups of faecal bacteria. 2. All faecal incubation systems studied generated large amounts of ammonia, particularly those in which bacterial counts fell during incubation. As normal faeces contain negligible amounts of urea this ammonia must have been generated from sources other than urea. 3. Ammonia was also generated by faeces delivered by sodium chloride enema, and by ileostomy fluid, indicating that the phenomenon is not confined to distal colonic contents. 4. Ammonia generation by incubated faeces was inhibited by prior autoclaving of the sample, but not by sterilization with gamma-irradiation. 5. Generation of ammonia by incubated stool was accompanied by release of large amounts of organic anion and a fall in pH. 6. These observations are interpreted as evidence that ammonia generated within the colon in situ is not derived exclusively from urea, but also from bacterial deamination of amino acids, peptides and proteins. Simultaneously bacterial activity generates large amounts of organacid. The presence of living bacteria is not essential for ammonia generation, provided that bacterial enzymes are present. 7. Bacterial generation of organic solute in faeces which have left the body is sufficiently rapid to cast serious doubts on the validity of faecal centrifugation, or other time-consuming techniques involving lengthy handling of faeces, as methods of obtaining extracellular faecal fluid for measurements of organic constituents or ammonia.", "contents": "Generation of ammonia from non-urea sources in a faecal incubation system. 1. A 25% faecal suspension in sodium chloride solution, incubated anaerobically at 37 degrees C for 48 h, showed excellent survival of all the main groups of faecal bacteria. 2. All faecal incubation systems studied generated large amounts of ammonia, particularly those in which bacterial counts fell during incubation. As normal faeces contain negligible amounts of urea this ammonia must have been generated from sources other than urea. 3. Ammonia was also generated by faeces delivered by sodium chloride enema, and by ileostomy fluid, indicating that the phenomenon is not confined to distal colonic contents. 4. Ammonia generation by incubated faeces was inhibited by prior autoclaving of the sample, but not by sterilization with gamma-irradiation. 5. Generation of ammonia by incubated stool was accompanied by release of large amounts of organic anion and a fall in pH. 6. These observations are interpreted as evidence that ammonia generated within the colon in situ is not derived exclusively from urea, but also from bacterial deamination of amino acids, peptides and proteins. Simultaneously bacterial activity generates large amounts of organacid. The presence of living bacteria is not essential for ammonia generation, provided that bacterial enzymes are present. 7. Bacterial generation of organic solute in faeces which have left the body is sufficiently rapid to cast serious doubts on the validity of faecal centrifugation, or other time-consuming techniques involving lengthy handling of faeces, as methods of obtaining extracellular faecal fluid for measurements of organic constituents or ammonia."}
{"id": "PMID:9222", "title": "The effect of pH on folic acid absorption in man.", "content": "1. Pteroylmonoglutamic acid (PteGlu) absorption has been measured by using the technique of small-intestinal perfusion with tritiated PteGlu in normal subjects and in patients with coeliac disease. 2. At similar intrajejunal pH, patients with untreated coeliac disease have significantly less PTEGlu than normal subjects and patients with treated coeliac disease. 3. The \"resting\" pH in the jejunum did not differ markedly between normal subjects and patients with coeliac disease. 4. Increasing pH decreased PteGlu absorption in patients with coeliac disease and in normal subjects. 5. These findings suggest that PteGlu malabsorption in coeliac disease is not due to abnormally high pH in the jejunum.", "contents": "The effect of pH on folic acid absorption in man. 1. Pteroylmonoglutamic acid (PteGlu) absorption has been measured by using the technique of small-intestinal perfusion with tritiated PteGlu in normal subjects and in patients with coeliac disease. 2. At similar intrajejunal pH, patients with untreated coeliac disease have significantly less PTEGlu than normal subjects and patients with treated coeliac disease. 3. The \"resting\" pH in the jejunum did not differ markedly between normal subjects and patients with coeliac disease. 4. Increasing pH decreased PteGlu absorption in patients with coeliac disease and in normal subjects. 5. These findings suggest that PteGlu malabsorption in coeliac disease is not due to abnormally high pH in the jejunum."}
{"id": "PMID:9268", "title": "The function of a psychiatric unit in a general hospital -- a five year experience.", "content": "The author reviews his five years experience with a psychiatric unit in a general hospital. He reviews the American Literature noting such units are thought to be important. There has been no discussion of the community roles of such units. From his experience, he recommends such units play a limited but specific function in the medical and mental health delivery system.", "contents": "The function of a psychiatric unit in a general hospital -- a five year experience. The author reviews his five years experience with a psychiatric unit in a general hospital. He reviews the American Literature noting such units are thought to be important. There has been no discussion of the community roles of such units. From his experience, he recommends such units play a limited but specific function in the medical and mental health delivery system."}
{"id": "PMID:9270", "title": "Antihistamines: pharmacology and clinical use.", "content": "Antihistamines are a diverse group of drugs which possess the ability to inhibit various histaminic actions. By and large, they bear a certain structural resemblance to histamine, and act principally to prevent histamine-receptor interaction through competition with histamine for histamine receptors. Consequently, they are helpful therapeutically in preventing, rather than reversing, histaminic actions. Individual antihistaminic drugs act to inhibit histaminic action at one or another histamine receptor (H1 or H2-receptor), but not at both receptors. The large number of antihistaminics which have been available for many years and employed chiefly as 'antiallergic' drugs are classified as H1-receptor inhibitors; they are most effective therapeutically in inhibiting manifestations of histamine-induced wheal and erythema formation and pruritus. H2-receptor inhibitors, agents which are able to inhibit histamine-induced gastric acid secretion, have been developed more recently. Antihistaminics in general and H1-receptor inhibitors in particular, exert a wide variety of pharmacological activities. Their use is frequently accompanied by undesirable side-effects, notably CNS depression, dryness of mucous membranes, and gastrointestinal effects. Used judiciously and in proper dosage, antihistaminic drugs are helpful in the control of allergic disorders, allergic rhinitis and urticaria in particular; newly developed H2-receptor inhibitors show therapeutic promise in the treatment of peptic ulceration.", "contents": "Antihistamines: pharmacology and clinical use. Antihistamines are a diverse group of drugs which possess the ability to inhibit various histaminic actions. By and large, they bear a certain structural resemblance to histamine, and act principally to prevent histamine-receptor interaction through competition with histamine for histamine receptors. Consequently, they are helpful therapeutically in preventing, rather than reversing, histaminic actions. Individual antihistaminic drugs act to inhibit histaminic action at one or another histamine receptor (H1 or H2-receptor), but not at both receptors. The large number of antihistaminics which have been available for many years and employed chiefly as 'antiallergic' drugs are classified as H1-receptor inhibitors; they are most effective therapeutically in inhibiting manifestations of histamine-induced wheal and erythema formation and pruritus. H2-receptor inhibitors, agents which are able to inhibit histamine-induced gastric acid secretion, have been developed more recently. Antihistaminics in general and H1-receptor inhibitors in particular, exert a wide variety of pharmacological activities. Their use is frequently accompanied by undesirable side-effects, notably CNS depression, dryness of mucous membranes, and gastrointestinal effects. Used judiciously and in proper dosage, antihistaminic drugs are helpful in the control of allergic disorders, allergic rhinitis and urticaria in particular; newly developed H2-receptor inhibitors show therapeutic promise in the treatment of peptic ulceration."}
{"id": "PMID:9273", "title": "Quantitative study of secondary structure of histones H1, H2A, and H4 in solution by infrared spectroscopy.", "content": "The secondary structure of histones H1, H2A, and H4 (F1, F2a2, and F2a1) has been quantitatively studied in heavy water (2H2O) solutions in a wide range of histone concentration, p2H, and concentration of sodium chloride using an improved infrared spectroscopy method. Under all conditions there are about 5--10% of alpha helix. Conditions favourable for aggregation induce formation of antiparallel pleated sheet structure to an extent of about 15% in H1 and H2A and about 30% in H4. When the p2H and concentration of NaCl are in the physiological range, there is the same content of this structure in H2A and H4 and none in H1.", "contents": "Quantitative study of secondary structure of histones H1, H2A, and H4 in solution by infrared spectroscopy. The secondary structure of histones H1, H2A, and H4 (F1, F2a2, and F2a1) has been quantitatively studied in heavy water (2H2O) solutions in a wide range of histone concentration, p2H, and concentration of sodium chloride using an improved infrared spectroscopy method. Under all conditions there are about 5--10% of alpha helix. Conditions favourable for aggregation induce formation of antiparallel pleated sheet structure to an extent of about 15% in H1 and H2A and about 30% in H4. When the p2H and concentration of NaCl are in the physiological range, there is the same content of this structure in H2A and H4 and none in H1."}
{"id": "PMID:9274", "title": "Photolysis of desmosine and isodesmosine by ultraviolet light.", "content": "1. Desmosine and isodesmosine were separated by ion-exchange and paper chromatography, after acid hydrolysis of purified elastin from beef ligamentum nuchae. The fractions obtained by ion-exchange chromatography were clearly mixtures of related compounds. The desmosine fraction could be resolved into seven compounds and the isodesmosine into four by paper chromatography. 2. Desmosine was maximally degraded by irradiation at 274 nm and isodesmosine at 285 nm. These wavelengths did not correspond to the absorption maxima of the cross links, but to shoulders of the main absorption peaks. 3. When irradiated at their optimum wavelengths, but at various pH, both desmosine and isodesmosine seemed quite stable at pH greater than 8.5. Between pH 8 and 5, the photolytic rate was maximum and decreased slightly at more acidic pH. Below pH 4.0, one of the products of photolysis was free lysine. 4. In analogy to the mechanism of the photolytic degradation of N-methyl pyridinium chloride, it appears that the (iso)desmosines were degraded via the formation of an open amino aldehyde, which was hydrolysed at acid pH to give free lysine and a substituted glutaconic aldehyde.", "contents": "Photolysis of desmosine and isodesmosine by ultraviolet light. 1. Desmosine and isodesmosine were separated by ion-exchange and paper chromatography, after acid hydrolysis of purified elastin from beef ligamentum nuchae. The fractions obtained by ion-exchange chromatography were clearly mixtures of related compounds. The desmosine fraction could be resolved into seven compounds and the isodesmosine into four by paper chromatography. 2. Desmosine was maximally degraded by irradiation at 274 nm and isodesmosine at 285 nm. These wavelengths did not correspond to the absorption maxima of the cross links, but to shoulders of the main absorption peaks. 3. When irradiated at their optimum wavelengths, but at various pH, both desmosine and isodesmosine seemed quite stable at pH greater than 8.5. Between pH 8 and 5, the photolytic rate was maximum and decreased slightly at more acidic pH. Below pH 4.0, one of the products of photolysis was free lysine. 4. In analogy to the mechanism of the photolytic degradation of N-methyl pyridinium chloride, it appears that the (iso)desmosines were degraded via the formation of an open amino aldehyde, which was hydrolysed at acid pH to give free lysine and a substituted glutaconic aldehyde."}
{"id": "PMID:9275", "title": "Effect of inhibitors on the substrate-dependent quenching of 9-aminoacridine fluorescence in inside-out membrane vesicles of Escherichia coli.", "content": "The effect of various inhibitors on the substrate-dependent quenching of the fluorescence of 9-aminoacridine was measured in inside-out membrane vesicles of Escherichia coli. The rate of fluorescence quenching in the presence of inhibitors was dependent on the rate of electron transfer through the respiratory chain with NADH, succinate, D-lactate or DL-glycerol 3-phosphate as substrates. Several patterns of response were given by the inhibitors. Inhibitors competitive with substrate, or those acting only on the dehydrogenases, gave a direct relationship between the extent of inhibition of oxidase activity and the rate of quenching. A biphasic relationship was given by 2-heptyl-4-hydroxyquinoline N-oxide and piericidin A which was due to these compounds acting both as inhibitors of the respiratory chain and, at higher concentrations, as uncoupling agents. Uncouplers inhibited fluorescence quenching with minimal inhibition of oxidase activity. The transmembrane pH difference was calculated from the extent of fluorescence quenching and the intravesicular volume. The maximum pH difference of 3.3--3.7 units was generated by each of the substrates tested.", "contents": "Effect of inhibitors on the substrate-dependent quenching of 9-aminoacridine fluorescence in inside-out membrane vesicles of Escherichia coli. The effect of various inhibitors on the substrate-dependent quenching of the fluorescence of 9-aminoacridine was measured in inside-out membrane vesicles of Escherichia coli. The rate of fluorescence quenching in the presence of inhibitors was dependent on the rate of electron transfer through the respiratory chain with NADH, succinate, D-lactate or DL-glycerol 3-phosphate as substrates. Several patterns of response were given by the inhibitors. Inhibitors competitive with substrate, or those acting only on the dehydrogenases, gave a direct relationship between the extent of inhibition of oxidase activity and the rate of quenching. A biphasic relationship was given by 2-heptyl-4-hydroxyquinoline N-oxide and piericidin A which was due to these compounds acting both as inhibitors of the respiratory chain and, at higher concentrations, as uncoupling agents. Uncouplers inhibited fluorescence quenching with minimal inhibition of oxidase activity. The transmembrane pH difference was calculated from the extent of fluorescence quenching and the intravesicular volume. The maximum pH difference of 3.3--3.7 units was generated by each of the substrates tested."}
{"id": "PMID:9276", "title": "8-Azidoacenine analogs of NAD+ and FAD. Synthesis and coenzyme properties with NAD+-dependent and FAD-dependent enzymes.", "content": "The synthesis and purification of the 8-azidoadenine analogs of NAD+ (azido-NAD+) and FAD (AZIDO-FAD) from 8-azidoadenosine 5'-phosphate and NMN+ or FMN, respectively, is described. The coenzyme analogs are characterized by absorption, nuclear magnetic resonance and circular dichroism spectra. The two latter methods indicate a folded structure of azido-NAD+ and azido-FAD. Upon irradiation at 300 mn in aqueous solution, a change of the ultraviolet absorption spectra of the coenzyme analogs indicates photolysis of the azido group. The coenzyme properties of azido-NAD+ are demonstrated with lactate, glutamate and alcohol dehydrogenase yielding 14, 154 and 60%, respectively, of the V observed with NAD+. Concomitantly, the Km values of the coenzyme analogs are 1.7, 3.5 and 3-fold higher than those of NAD+. Azido-FAD is shown to be coenzyme of apo-glucose oxidase. The recovery of activity, however, is much slower in the presence of azido-FAD than with FAD. A final value of 66% of the activity with FAD is obtained. With apo-D-amino acid oxidase, azido-FAD is completely inactive, although it is specifically bound to the enzyme.", "contents": "8-Azidoacenine analogs of NAD+ and FAD. Synthesis and coenzyme properties with NAD+-dependent and FAD-dependent enzymes. The synthesis and purification of the 8-azidoadenine analogs of NAD+ (azido-NAD+) and FAD (AZIDO-FAD) from 8-azidoadenosine 5'-phosphate and NMN+ or FMN, respectively, is described. The coenzyme analogs are characterized by absorption, nuclear magnetic resonance and circular dichroism spectra. The two latter methods indicate a folded structure of azido-NAD+ and azido-FAD. Upon irradiation at 300 mn in aqueous solution, a change of the ultraviolet absorption spectra of the coenzyme analogs indicates photolysis of the azido group. The coenzyme properties of azido-NAD+ are demonstrated with lactate, glutamate and alcohol dehydrogenase yielding 14, 154 and 60%, respectively, of the V observed with NAD+. Concomitantly, the Km values of the coenzyme analogs are 1.7, 3.5 and 3-fold higher than those of NAD+. Azido-FAD is shown to be coenzyme of apo-glucose oxidase. The recovery of activity, however, is much slower in the presence of azido-FAD than with FAD. A final value of 66% of the activity with FAD is obtained. With apo-D-amino acid oxidase, azido-FAD is completely inactive, although it is specifically bound to the enzyme."}
{"id": "PMID:9277", "title": "Glutathione reductase from human erythrocytes. Catalytic properties and aggregation.", "content": "The catalytic properties of glutathione reductase from human erythrocytes have been studied over a range of buffer conditions and substrate concentrations. This study provides optimal conditions for determining the basic kinetic parameters of the enzyme. The catalytic behaviour of glutathione reductase is consistent with spatially separated binding sites for its substrates. In certain assays anomalies were observed which are correlated with an inactivation of the enzyme by NADPH. Concurrent sedimentation experiments showed that NADPH promoted aggregation of the enzyme. Both inactivation and aggregation could be connected with oxidation of thiols at the active site. The relation of the properties of glutathione reductase to cellular conditions is discussed.", "contents": "Glutathione reductase from human erythrocytes. Catalytic properties and aggregation. The catalytic properties of glutathione reductase from human erythrocytes have been studied over a range of buffer conditions and substrate concentrations. This study provides optimal conditions for determining the basic kinetic parameters of the enzyme. The catalytic behaviour of glutathione reductase is consistent with spatially separated binding sites for its substrates. In certain assays anomalies were observed which are correlated with an inactivation of the enzyme by NADPH. Concurrent sedimentation experiments showed that NADPH promoted aggregation of the enzyme. Both inactivation and aggregation could be connected with oxidation of thiols at the active site. The relation of the properties of glutathione reductase to cellular conditions is discussed."}
{"id": "PMID:9278", "title": "Phosphate binding to chromatophores of Rhodospirillum rubrum.", "content": "Equilibrium dialysis has been used to determine the binding of phosphate to chromatophores of Rhodospirillum rubrum. Assuming a complete exchange of the added 32Pi with endogenous phosphate, the saturation with phosphate retained in any form by chromatophores was reached at about 20 nmoles Pi per mg of bacteriochlorophyll. The retention of phosphate had a pH optimum at pH 6.5 to 6.8. At pH 8.0 only chromatophores which have not been liberated from DNA and RNA show a considerable retention of phosphate. However, illumination of chromatophores prior to dialysis in the presence of ADP leads to a retention of phosphate at pH 8.0 which persists during dark dialysis in the absence of added magnesium.", "contents": "Phosphate binding to chromatophores of Rhodospirillum rubrum. Equilibrium dialysis has been used to determine the binding of phosphate to chromatophores of Rhodospirillum rubrum. Assuming a complete exchange of the added 32Pi with endogenous phosphate, the saturation with phosphate retained in any form by chromatophores was reached at about 20 nmoles Pi per mg of bacteriochlorophyll. The retention of phosphate had a pH optimum at pH 6.5 to 6.8. At pH 8.0 only chromatophores which have not been liberated from DNA and RNA show a considerable retention of phosphate. However, illumination of chromatophores prior to dialysis in the presence of ADP leads to a retention of phosphate at pH 8.0 which persists during dark dialysis in the absence of added magnesium."}
{"id": "PMID:9279", "title": "The role of interchain disulphide bridges in the conformational stability of human immunoglobulin G1 subclass. Hydrogen-deuterium exchange studies.", "content": "The hydrogen-deuterium exchange data of human immunoglobulin G1 (IgG1) are interpreted by assuming fast fluctuations of the protein conformation, through which the peptide groups become exposed to the solvent. The probability of solvent exposure of peptide hydrogens reflects a rather loose conformation for native IgG in comparison with other globular proteins. The probability of solvent exposure is greater than 10(-3) for half of the peptide groups, which shows that the conformational transitions by which these groups are exposed to the solvent are accompanied by changes in standard free energy less than 17 kJ/mol (4 kcal/mol). In the range of pH 6.2-8.45, at 25 degrees C no gross conformational changes are reflected in the hydrogen-deuterium exchange behaviour of the native, the reduced-nonalkylated-reassociated and the reduced-S-alkylated-reassociated IgG1. No difference could be detected in the conformational stability of the native and reoxidised reassociated IgG1 proteins. The lack of inter-subunit disulphide bridges in S-alkylated-reassociated molecules results in an increased conformational motility. This destabilization of protein conformation affects about 90% of the peptide groups covered by the measurements, and corresponds to changes in standard free energy of 8 kJ/mol on the average.", "contents": "The role of interchain disulphide bridges in the conformational stability of human immunoglobulin G1 subclass. Hydrogen-deuterium exchange studies. The hydrogen-deuterium exchange data of human immunoglobulin G1 (IgG1) are interpreted by assuming fast fluctuations of the protein conformation, through which the peptide groups become exposed to the solvent. The probability of solvent exposure of peptide hydrogens reflects a rather loose conformation for native IgG in comparison with other globular proteins. The probability of solvent exposure is greater than 10(-3) for half of the peptide groups, which shows that the conformational transitions by which these groups are exposed to the solvent are accompanied by changes in standard free energy less than 17 kJ/mol (4 kcal/mol). In the range of pH 6.2-8.45, at 25 degrees C no gross conformational changes are reflected in the hydrogen-deuterium exchange behaviour of the native, the reduced-nonalkylated-reassociated and the reduced-S-alkylated-reassociated IgG1. No difference could be detected in the conformational stability of the native and reoxidised reassociated IgG1 proteins. The lack of inter-subunit disulphide bridges in S-alkylated-reassociated molecules results in an increased conformational motility. This destabilization of protein conformation affects about 90% of the peptide groups covered by the measurements, and corresponds to changes in standard free energy of 8 kJ/mol on the average."}
{"id": "PMID:9280", "title": "Equilibrium studies on the refolding and reactivation of rabbit-muscle aldolase after acid dissociation.", "content": "Dissociation, denaturation, and deactivation of aldolase from rabbit muscle in the acid pH range have been investigated using sedimentation analysis, fluorescence, circular dichroism, and activity tests. Under comparable experimental conditions the pH-dependent profiles of deactivation and denaturation parallel the dissociation of the enzyme. In the range of dissociation at pH4-5tetramers and monomers are in equilibrium. Intrinsic chromophores and far-ultraviolet circular dichroism suggest the transition to be a complex multistep process. At pH approximately 2.3 the enzyme is split into its fully inactive monomers which still contain some residual secondary structure. After reassociation under optimum conditions (0.2 M phosphate buffer pH 7.6, 1 mM EDTA, 0.1 mM dithiothreitol, 0 degrees C, enzyme concentration 0.4-59 mug/ml) up to 95% enzymic activity is recovered which belongs to a renatured tetrameric species indistinguishable from the native enzyme by all available biochemical and physicochemical criteria.", "contents": "Equilibrium studies on the refolding and reactivation of rabbit-muscle aldolase after acid dissociation. Dissociation, denaturation, and deactivation of aldolase from rabbit muscle in the acid pH range have been investigated using sedimentation analysis, fluorescence, circular dichroism, and activity tests. Under comparable experimental conditions the pH-dependent profiles of deactivation and denaturation parallel the dissociation of the enzyme. In the range of dissociation at pH4-5tetramers and monomers are in equilibrium. Intrinsic chromophores and far-ultraviolet circular dichroism suggest the transition to be a complex multistep process. At pH approximately 2.3 the enzyme is split into its fully inactive monomers which still contain some residual secondary structure. After reassociation under optimum conditions (0.2 M phosphate buffer pH 7.6, 1 mM EDTA, 0.1 mM dithiothreitol, 0 degrees C, enzyme concentration 0.4-59 mug/ml) up to 95% enzymic activity is recovered which belongs to a renatured tetrameric species indistinguishable from the native enzyme by all available biochemical and physicochemical criteria."}
{"id": "PMID:9281", "title": "The non-convalent binding of small molecules by ligandin. Interactions with steroids and their conjugates, fatty acids, bromosulphophthalein carcinogens, glutathione and realted compounds.", "content": "1. Equilibrium dialysis studies have been made of the binding of a number of small molecules by rat ligandin. Direct measurements of binding together with competition experiments indicated that bromosulphophthalein, oestrone sulphate and dehydroepiandrosterone sulphate each bind at the same single primary binding site with association constants of 1.1 X 10(7), 6.6 X 10(5) and 2.6 X 10(5) 1/mol respectively at pH 7.0,IO.16M,4 degrees C. As well as bromosulphophthalein and dehydroepiandrosterone sulphate, a number of strucurally similar organic anions including 2-hydroxyoestradiol-glutathione oestrone glycyronide, N-methyl-4-aminoazobenzene-glutathione and several bile acids, were able to displace oestrone sulphate from ligandin in a manner consistent with competition at a single binding site. From these experiments association constants for the competing ligands were derived; these were inthe range 1 X 10(4)-1 X 10(6) 1/mol. 2. Ligandin was found to bind a number of compounds for which, because of their low aqueous solubilities relative to their binding affinities complete  binding isotherms could bot be obtained. These included several steroids (but not cortisol), 20-methylcholanthrene, diethylstilboestrol, oleate and palmitate. Oestrone sulphate was able to compete with these ligands for binding and the results of the competition experiments were interpretable in terms of 1:1 competition at a single binding site. 3. In general the conjugation of non-polar ligands with sulphate or glutathione resulted in increased affinities, but such increases were relatively small (approximately 15% in therms of free energy) implying that the main driving force for the binding of both the conjugated and unconjugated species was the hydrophobic effect. This conclusion is borne out by the observations that both oestrone and its sulphate showed slight increases in affinity with increase in ionic strength, as would be expected for hydrophobic interactions. 4. As well as non-polar compounds and organic anions, ligandin was also found to bind sulphate and glucuronate to a measurable degree, and to interact quite strongly with glutathione. For the latter compound a single binding site was found with an association constant of 1 X 10(5) 1/mol. Glutathione was able to cause the dissociation of the ligandin-oestrone sulphate complex, but this effect was not explicable in terms of simple 1:1 competition. 5. Both oestrone and oestrone sulphare were bound most strongly at pH 6-7, the affinity of the protein for these ligands falling off quite sharply on either side of this maximum. 6. The affinities of ligandin for bromosulphophthalein, steroids and their conjugates, diethylstilboestrol and N,N-dimethyl-4-aminoazobenzene are similar in magnitude to those of serum albumin and aminoazodye-binding protein A (B. Ketterer, E. Tipping, J.F. Hackney and D. Beale, 1976).", "contents": "The non-convalent binding of small molecules by ligandin. Interactions with steroids and their conjugates, fatty acids, bromosulphophthalein carcinogens, glutathione and realted compounds. 1. Equilibrium dialysis studies have been made of the binding of a number of small molecules by rat ligandin. Direct measurements of binding together with competition experiments indicated that bromosulphophthalein, oestrone sulphate and dehydroepiandrosterone sulphate each bind at the same single primary binding site with association constants of 1.1 X 10(7), 6.6 X 10(5) and 2.6 X 10(5) 1/mol respectively at pH 7.0,IO.16M,4 degrees C. As well as bromosulphophthalein and dehydroepiandrosterone sulphate, a number of strucurally similar organic anions including 2-hydroxyoestradiol-glutathione oestrone glycyronide, N-methyl-4-aminoazobenzene-glutathione and several bile acids, were able to displace oestrone sulphate from ligandin in a manner consistent with competition at a single binding site. From these experiments association constants for the competing ligands were derived; these were inthe range 1 X 10(4)-1 X 10(6) 1/mol. 2. Ligandin was found to bind a number of compounds for which, because of their low aqueous solubilities relative to their binding affinities complete  binding isotherms could bot be obtained. These included several steroids (but not cortisol), 20-methylcholanthrene, diethylstilboestrol, oleate and palmitate. Oestrone sulphate was able to compete with these ligands for binding and the results of the competition experiments were interpretable in terms of 1:1 competition at a single binding site. 3. In general the conjugation of non-polar ligands with sulphate or glutathione resulted in increased affinities, but such increases were relatively small (approximately 15% in therms of free energy) implying that the main driving force for the binding of both the conjugated and unconjugated species was the hydrophobic effect. This conclusion is borne out by the observations that both oestrone and its sulphate showed slight increases in affinity with increase in ionic strength, as would be expected for hydrophobic interactions. 4. As well as non-polar compounds and organic anions, ligandin was also found to bind sulphate and glucuronate to a measurable degree, and to interact quite strongly with glutathione. For the latter compound a single binding site was found with an association constant of 1 X 10(5) 1/mol. Glutathione was able to cause the dissociation of the ligandin-oestrone sulphate complex, but this effect was not explicable in terms of simple 1:1 competition. 5. Both oestrone and oestrone sulphare were bound most strongly at pH 6-7, the affinity of the protein for these ligands falling off quite sharply on either side of this maximum. 6. The affinities of ligandin for bromosulphophthalein, steroids and their conjugates, diethylstilboestrol and N,N-dimethyl-4-aminoazobenzene are similar in magnitude to those of serum albumin and aminoazodye-binding protein A (B. Ketterer, E. Tipping, J.F. Hackney and D. Beale, 1976)."}
{"id": "PMID:9282", "title": "Specificity and properties of the destabilization, induced by initiation factor IF-3, of ternary complexes of the 30-S ribosomal subunit, aminoacyl-tRNA and polynucleotides.", "content": "Initiation factor IF-3 causes the destabilization of preformed ternary complexes of 30-S ribosomal subunit, codons and aminoacyl-tRNAs or peptidyl-tRNA. This destabilization is dilution-dependent and affects all ternary complexes with the exception of those containing the initiator fMet-tRNA, which remain more resistant to IF-3-induced destabilization under the various conditions studied. Several possible reasons for this specificity have been examined. It was found that the basis for the specificity is not: (a) an intrinsic greater stability of the ternary complexes containing fMet-tRNA, (b) the amoung of aminoacyl-tRNA bound to the ribosome, (c) the conditions under which the ternary complex is made or (d) the formylation of the amino group. On the other hand, the nature of the polynucleotide in response to which the ternary complex is formed was found to influence the amount of aminoacyl-tRan bound to the ribosome, and to some extent the amount of aminoacyl-tRNA which can be relased. The ternary complex containing the mischarged initiator tRNA fVal-tRNAfMet displays greater resistance to the IF-3-induced destabilization than the complex containing fVal-tRNAVal. These results indicate that the specificity of the IF-3 activity is due to the special structural feature of the initiator tRNA molecule and to some extent to the nature of the polynucleotide. The IF-3-induced destabilization of ternary complexes was found to be little affected by variations in reaction conditons, so that this IF-3 activity can be used to measure the stoichiometric binding of IF-3 to the ribosome over a broad range of pH and K+ and Mg2+ concentrations. Several antibiotics have been tested for their capacity to interfere with this reaction; only high concentrations of tetracycline blocked this IF-3 activity.", "contents": "Specificity and properties of the destabilization, induced by initiation factor IF-3, of ternary complexes of the 30-S ribosomal subunit, aminoacyl-tRNA and polynucleotides. Initiation factor IF-3 causes the destabilization of preformed ternary complexes of 30-S ribosomal subunit, codons and aminoacyl-tRNAs or peptidyl-tRNA. This destabilization is dilution-dependent and affects all ternary complexes with the exception of those containing the initiator fMet-tRNA, which remain more resistant to IF-3-induced destabilization under the various conditions studied. Several possible reasons for this specificity have been examined. It was found that the basis for the specificity is not: (a) an intrinsic greater stability of the ternary complexes containing fMet-tRNA, (b) the amoung of aminoacyl-tRNA bound to the ribosome, (c) the conditions under which the ternary complex is made or (d) the formylation of the amino group. On the other hand, the nature of the polynucleotide in response to which the ternary complex is formed was found to influence the amount of aminoacyl-tRan bound to the ribosome, and to some extent the amount of aminoacyl-tRNA which can be relased. The ternary complex containing the mischarged initiator tRNA fVal-tRNAfMet displays greater resistance to the IF-3-induced destabilization than the complex containing fVal-tRNAVal. These results indicate that the specificity of the IF-3 activity is due to the special structural feature of the initiator tRNA molecule and to some extent to the nature of the polynucleotide. The IF-3-induced destabilization of ternary complexes was found to be little affected by variations in reaction conditons, so that this IF-3 activity can be used to measure the stoichiometric binding of IF-3 to the ribosome over a broad range of pH and K+ and Mg2+ concentrations. Several antibiotics have been tested for their capacity to interfere with this reaction; only high concentrations of tetracycline blocked this IF-3 activity."}
{"id": "PMID:9283", "title": "Amino-acid sequence of a coelenterate toxin: toxin II from Anemonia sulcata.", "content": "Toxin II from Anemonia sulcata, the main component of the sea anemone venom, consists of 47 amino acid residues which are interconnected by three disulfide bridges. The S-aminoethylated polypeptide was coupled to activated glass beads and sequenced to position 33 by automated solid-phase Edman degradation. Blanks arising from anchor points and the rest of the sequence were determined from tryptic peptides of the [14C]carboxymethylated toxin. Toxin II shows no significant homologies with other known sequences of neurotoxins or cardiotoxins. It might constitute a new class of polypeptide toxins.", "contents": "Amino-acid sequence of a coelenterate toxin: toxin II from Anemonia sulcata. Toxin II from Anemonia sulcata, the main component of the sea anemone venom, consists of 47 amino acid residues which are interconnected by three disulfide bridges. The S-aminoethylated polypeptide was coupled to activated glass beads and sequenced to position 33 by automated solid-phase Edman degradation. Blanks arising from anchor points and the rest of the sequence were determined from tryptic peptides of the [14C]carboxymethylated toxin. Toxin II shows no significant homologies with other known sequences of neurotoxins or cardiotoxins. It might constitute a new class of polypeptide toxins."}
{"id": "PMID:9284", "title": "The role of lysine-41 in ribonuclease A studied by proton-magnetic-resonance spectroscopy of guanidinated ribonuclease A.", "content": "Ribonuclease A has been guanidinated at the lysine residues and the nona-guanidinated and deca-guanidinated (fully substituted) products separated. In confirmation of an earlier report by Glick and Barnard (1970), it has been shown by chemical procedures that the former derivative is not reacted at lysine-41. Guanidination of lysine-41 to produce the fully substituted product causes loss of enzymic activity without any apparent change of conformation, as tested by conformational comparisons (using proton magnetic resonance spectroscopy) including (a) difference spectroscopy, evidence for the involvement of lysine-41 in a catalytic role in the enzyme. Dimethylation of lysine-41 of nona-guanidinated ribonuclease A produces sharp proton resonances which shifts as the dimethylamino group is titrated and allow the determination of an apparent pK of 8.8 for unsubstituted lysine-41.", "contents": "The role of lysine-41 in ribonuclease A studied by proton-magnetic-resonance spectroscopy of guanidinated ribonuclease A. Ribonuclease A has been guanidinated at the lysine residues and the nona-guanidinated and deca-guanidinated (fully substituted) products separated. In confirmation of an earlier report by Glick and Barnard (1970), it has been shown by chemical procedures that the former derivative is not reacted at lysine-41. Guanidination of lysine-41 to produce the fully substituted product causes loss of enzymic activity without any apparent change of conformation, as tested by conformational comparisons (using proton magnetic resonance spectroscopy) including (a) difference spectroscopy, evidence for the involvement of lysine-41 in a catalytic role in the enzyme. Dimethylation of lysine-41 of nona-guanidinated ribonuclease A produces sharp proton resonances which shifts as the dimethylamino group is titrated and allow the determination of an apparent pK of 8.8 for unsubstituted lysine-41."}
{"id": "PMID:9285", "title": "Biosynthesis of stizolobinic acid and stizolobic acid in higher plants. An enzyme system(s) catalyzing the conversion of dihydroxyphenylalanine into stizolobinic acid and stizolobic acid from etiolated seedlings of Stizolobium hassjoo.", "content": "It was demonstrated that an enzyme system(s) extracted from etiolated seedlings of Stizolobium hassjoo catalyzed the conversion of L-dihydroxyphenylalanine into stizolobinic acid, alpha-amino-6-carboxy-2-oxo-2H-pyran-3-propionic acid, and stizolobic acid, alpha-amino-6-carboxy-2-oxo-2H-pyran-4-propionic acid, in the presence of NADP+ or NAD+ under aerobic conditions. Enzymically synthesized radioactive stizolobinic acid and stizolobic acid isolated from the reaction mixtures were purified and confirmed to have constant specific radioactivities by cocrystallization with authentic samples. Maximal activity of the enzyme preparation was obtained by using an insoluble polyphenol adsorbent (Polyclar AT) and a reducing agent (araboascorbic acid) in the extraction medium and by subsequent fractionation of the extract with ammonium sulfate followed by Sephadex G-25 gel filtration. Catalytic activity of the enzyme preparation was more unstable under aerobic condition than anaerobic. Attempts to stabilise the enzyme activity were made by the use of many substances which are known to stabilise other enzymes or expected to arrest the inactivation. Evidence is provided in this paper that the previously proposed biosynthetic pathways of stizolobinic acid and stizolobic acid from dihydroxyphenylalanine proceeded in the cell-free system from etiolated seedlings of S. hassjoo.", "contents": "Biosynthesis of stizolobinic acid and stizolobic acid in higher plants. An enzyme system(s) catalyzing the conversion of dihydroxyphenylalanine into stizolobinic acid and stizolobic acid from etiolated seedlings of Stizolobium hassjoo. It was demonstrated that an enzyme system(s) extracted from etiolated seedlings of Stizolobium hassjoo catalyzed the conversion of L-dihydroxyphenylalanine into stizolobinic acid, alpha-amino-6-carboxy-2-oxo-2H-pyran-3-propionic acid, and stizolobic acid, alpha-amino-6-carboxy-2-oxo-2H-pyran-4-propionic acid, in the presence of NADP+ or NAD+ under aerobic conditions. Enzymically synthesized radioactive stizolobinic acid and stizolobic acid isolated from the reaction mixtures were purified and confirmed to have constant specific radioactivities by cocrystallization with authentic samples. Maximal activity of the enzyme preparation was obtained by using an insoluble polyphenol adsorbent (Polyclar AT) and a reducing agent (araboascorbic acid) in the extraction medium and by subsequent fractionation of the extract with ammonium sulfate followed by Sephadex G-25 gel filtration. Catalytic activity of the enzyme preparation was more unstable under aerobic condition than anaerobic. Attempts to stabilise the enzyme activity were made by the use of many substances which are known to stabilise other enzymes or expected to arrest the inactivation. Evidence is provided in this paper that the previously proposed biosynthetic pathways of stizolobinic acid and stizolobic acid from dihydroxyphenylalanine proceeded in the cell-free system from etiolated seedlings of S. hassjoo."}
{"id": "PMID:9286", "title": "Isolation and partial characterization of the cytochrome oxidase from Rhodopseudomonas palustris.", "content": "The cytochrome oxidase (EC 1.9.3.1) of Rhodopseudomonas palustris was extracted with Triton X-100 plus KCl, from the membrane fraction of cells grown aerobically in the dark. The solubilized enzyme was purified by (NH4)2SO4 precipitation and chromatography on DEAE-cellulose. The purification resulted in a 108-fold enrichment of cytochrome oxidase on the basis of specific activity when compared to the membrane fraction. The purified enzyme was phosphate-sensitive (less than mM), oxidized reduced bovine, horse and yeast cytochrome c, and was inhibited 50% by 0.5 muM KCN or 7 muM NaN3. The native purified preparation migrated as one band in polyacrylamide gel electrophoresis. In the presence of dodecylsulfate four major polypeptides with apparent molecular weights of 30500, 25500, 12200 and 9500 were observed. The enzyme reacted with oxygen via cytochrome o. The purified preparation contained cytochrome c but was free of flavoproteins and NADH-linked and succinate-linked enzyme activities of the respiratory chain.", "contents": "Isolation and partial characterization of the cytochrome oxidase from Rhodopseudomonas palustris. The cytochrome oxidase (EC 1.9.3.1) of Rhodopseudomonas palustris was extracted with Triton X-100 plus KCl, from the membrane fraction of cells grown aerobically in the dark. The solubilized enzyme was purified by (NH4)2SO4 precipitation and chromatography on DEAE-cellulose. The purification resulted in a 108-fold enrichment of cytochrome oxidase on the basis of specific activity when compared to the membrane fraction. The purified enzyme was phosphate-sensitive (less than mM), oxidized reduced bovine, horse and yeast cytochrome c, and was inhibited 50% by 0.5 muM KCN or 7 muM NaN3. The native purified preparation migrated as one band in polyacrylamide gel electrophoresis. In the presence of dodecylsulfate four major polypeptides with apparent molecular weights of 30500, 25500, 12200 and 9500 were observed. The enzyme reacted with oxygen via cytochrome o. The purified preparation contained cytochrome c but was free of flavoproteins and NADH-linked and succinate-linked enzyme activities of the respiratory chain."}
{"id": "PMID:9287", "title": "Distinct steps in the specific binding of tRNA to aminoacyl-tRNA synthetase. Temperature-jump studies on the serine-specific system from yeast and the tyrosine-specific system from Escherichia coli.", "content": "The kinetics of the interaction of tRNASer and seryl-tRNA synthetase from yeast as well as of tRNATyr and tyrosyl-tRNA synthetase from Escherichia coli have been investigated by temperature-jump experiments. It could be shown that complex formation proceeds in two distinct steps. This was demonstrated for both the first and the second binding site. The two-step mechanism was deduced from the characteristic concentration dependence of the relaxation times. Seryl-tRNA synthetase recombines with the first tRNA to form an intermediate complex (kI12, kI21), which is transformed in a fast reaction to the final 1:1 complex (kI23, kI32). At pH 7.2 with 0.1 M KCl the rate constants are: kI12 = 2.7 X 10(8) M-1 S-1; kI23, kI32). At pH 7.2 with 0.1 M KCl the rate constants are: kI12 = 2.7 x 10(8) M-1 S-1; kI21 = 220 S-1; kI23 = 760 S-1; kI32 = 330 S-1. The 1:1 complex can bind a second tRNA. At pH 7.2 without added salt the rate constants are: KII2 = 0.9 X 10(8) M-1 S-1; kII21 = 270 S-1; kII23 = 120 S-1; kII32 = 1250 S-1. The tyrosine-specific system behaves very similarly to the serine-specific system. Data are given for pH 7.2 (pH 6.0) for the binding of the second tRNA: kII12 = 1 X 10(8) (2.5 X 10(8)) M-1 S-1; kII21 = 470 (170) S-1; kII23 = 150 (530) S-1; kII32 = 1540 (720) S-1. The kinetic results are discussed in terms of their relevance to the recognition process and their relation to the anticooperative binding behaviour of tRNA to synthetase.", "contents": "Distinct steps in the specific binding of tRNA to aminoacyl-tRNA synthetase. Temperature-jump studies on the serine-specific system from yeast and the tyrosine-specific system from Escherichia coli. The kinetics of the interaction of tRNASer and seryl-tRNA synthetase from yeast as well as of tRNATyr and tyrosyl-tRNA synthetase from Escherichia coli have been investigated by temperature-jump experiments. It could be shown that complex formation proceeds in two distinct steps. This was demonstrated for both the first and the second binding site. The two-step mechanism was deduced from the characteristic concentration dependence of the relaxation times. Seryl-tRNA synthetase recombines with the first tRNA to form an intermediate complex (kI12, kI21), which is transformed in a fast reaction to the final 1:1 complex (kI23, kI32). At pH 7.2 with 0.1 M KCl the rate constants are: kI12 = 2.7 X 10(8) M-1 S-1; kI23, kI32). At pH 7.2 with 0.1 M KCl the rate constants are: kI12 = 2.7 x 10(8) M-1 S-1; kI21 = 220 S-1; kI23 = 760 S-1; kI32 = 330 S-1. The 1:1 complex can bind a second tRNA. At pH 7.2 without added salt the rate constants are: KII2 = 0.9 X 10(8) M-1 S-1; kII21 = 270 S-1; kII23 = 120 S-1; kII32 = 1250 S-1. The tyrosine-specific system behaves very similarly to the serine-specific system. Data are given for pH 7.2 (pH 6.0) for the binding of the second tRNA: kII12 = 1 X 10(8) (2.5 X 10(8)) M-1 S-1; kII21 = 470 (170) S-1; kII23 = 150 (530) S-1; kII32 = 1540 (720) S-1. The kinetic results are discussed in terms of their relevance to the recognition process and their relation to the anticooperative binding behaviour of tRNA to synthetase."}
{"id": "PMID:9288", "title": "Mechanism of discrimination between cognate and non-cognate tRNAs by phenylalanyl-tRNA synthetase from yeast.", "content": "The interaction between phenylalanyl-tRNA synthetase from yeast and Escherichia coli and tRNAPhe (yeast), tRNASer (yeast), tRNA1Val (E. coli) has been investigated by ultracentrifugation analysis, fluorescence titrations and fast kinetic techniques. The fluorescence of the Y-base of tRNAPhe and the intrinsic fluorescence of the synthetases have been used as optical indicators. 1. Specific complexes between phenylalanyl-tRNA synthetase and tRNAPhe from yeast are formed in a two-step mechanism: a nearly diffusion-controlled recombination is followed by a fast conformational transition. Binding constants, rate constants and changes in the quantum yield of the Y-base fluorescence upon binding are given under a variety of conditions with respect to pH, added salt, concentration of Mg2+ ions and temperature. 2. Heterologous complexes between phenylalanyl-tRNA synthetase (E. coli) and tRNAPhe (yeast) are formed in a similar two-step mechanism as the specific complexes; the conformational transition, however, is slower by a factor 4-5. 3. Formation of non-specific complexes between phenylalanyl-tRNA synthetase (yeast) and tRNATyr (E. coli) proceeds in a one-step mechanism. Phenylalanyl-tRNA synthetase (yeast) binds either two molecules of tRNAPhe (yeast) or only one molecule of tRNATyr (E. coli); tRNA1Val (E. coli) or tRNASer (yeast) are also bound in a 1:1 stoichiometry. Binding constants for complexes of phenylalanyl-tRNA synthetase (yeast) and tRNATyr (E. coli) are determined under a variety of conditions. In contrast to specific complex formation, non-specific binding is disfavoured by the presence of Mg2+ ions, and is not affected by pH and the presence of pyrophosphate. The difference in the stabilities of specific and non-specific complexes can be varied by a factor of 2--100 depending on the ionic conditions. Discrimination of cognate and non-cognate tRNA by phenylalanyl-tRNA synthetase (yeast) is discussed in terms of the binding mechanism, the topology of the binding sites, the nature of interacting forces and the relation between specificity and ionic conditions.", "contents": "Mechanism of discrimination between cognate and non-cognate tRNAs by phenylalanyl-tRNA synthetase from yeast. The interaction between phenylalanyl-tRNA synthetase from yeast and Escherichia coli and tRNAPhe (yeast), tRNASer (yeast), tRNA1Val (E. coli) has been investigated by ultracentrifugation analysis, fluorescence titrations and fast kinetic techniques. The fluorescence of the Y-base of tRNAPhe and the intrinsic fluorescence of the synthetases have been used as optical indicators. 1. Specific complexes between phenylalanyl-tRNA synthetase and tRNAPhe from yeast are formed in a two-step mechanism: a nearly diffusion-controlled recombination is followed by a fast conformational transition. Binding constants, rate constants and changes in the quantum yield of the Y-base fluorescence upon binding are given under a variety of conditions with respect to pH, added salt, concentration of Mg2+ ions and temperature. 2. Heterologous complexes between phenylalanyl-tRNA synthetase (E. coli) and tRNAPhe (yeast) are formed in a similar two-step mechanism as the specific complexes; the conformational transition, however, is slower by a factor 4-5. 3. Formation of non-specific complexes between phenylalanyl-tRNA synthetase (yeast) and tRNATyr (E. coli) proceeds in a one-step mechanism. Phenylalanyl-tRNA synthetase (yeast) binds either two molecules of tRNAPhe (yeast) or only one molecule of tRNATyr (E. coli); tRNA1Val (E. coli) or tRNASer (yeast) are also bound in a 1:1 stoichiometry. Binding constants for complexes of phenylalanyl-tRNA synthetase (yeast) and tRNATyr (E. coli) are determined under a variety of conditions. In contrast to specific complex formation, non-specific binding is disfavoured by the presence of Mg2+ ions, and is not affected by pH and the presence of pyrophosphate. The difference in the stabilities of specific and non-specific complexes can be varied by a factor of 2--100 depending on the ionic conditions. Discrimination of cognate and non-cognate tRNA by phenylalanyl-tRNA synthetase (yeast) is discussed in terms of the binding mechanism, the topology of the binding sites, the nature of interacting forces and the relation between specificity and ionic conditions."}
{"id": "PMID:9289", "title": "Experimental infusion thrombophlebitis. Importance of the infusion rate.", "content": "The importance of the method of administration of acid glucose infusions for the venous inflammatory response has been investigated in two series of experimental trials. 60 ml of 5% glucose solution was administered into rabbit-ear veins in three ways: 1) continuously over 5 hours (slow infusion), 2) continuously over 1 hour (rapid infusion), 3) discontinuously during 2 X 30 minutes with an interval of 4 hours (discontinuous infusion). Microscopical examination of the veins revealed that the inflammatory changes were less pronounced after rapid and discontinuous infusions than after slow infusions.", "contents": "Experimental infusion thrombophlebitis. Importance of the infusion rate. The importance of the method of administration of acid glucose infusions for the venous inflammatory response has been investigated in two series of experimental trials. 60 ml of 5% glucose solution was administered into rabbit-ear veins in three ways: 1) continuously over 5 hours (slow infusion), 2) continuously over 1 hour (rapid infusion), 3) discontinuously during 2 X 30 minutes with an interval of 4 hours (discontinuous infusion). Microscopical examination of the veins revealed that the inflammatory changes were less pronounced after rapid and discontinuous infusions than after slow infusions."}
{"id": "PMID:9290", "title": "Experimental infusion thrombophlebitis. Importance of the pH of glucose solutions.", "content": "An experimental method is presented, which compares the tendency of different infusions to cause thrombophlebitis. It is based ona quantitative histological analysis of the inflammatory changes in the veins of rabbit ears after infusions under standardized conditions. By means of this method the inflammatory changes in the veins have been shown to be significantly less pronounced when the pH of glucose solutions is altered from 3.0 to 3.6. This pH change has been prescribed in the 1971 corrections to Pharmacopoea Nordica 1963. By complete neutralization of 5% glucose a further reduction of the damage to the veins has been obtained. For this purpose phosphate buffer is recommended.", "contents": "Experimental infusion thrombophlebitis. Importance of the pH of glucose solutions. An experimental method is presented, which compares the tendency of different infusions to cause thrombophlebitis. It is based ona quantitative histological analysis of the inflammatory changes in the veins of rabbit ears after infusions under standardized conditions. By means of this method the inflammatory changes in the veins have been shown to be significantly less pronounced when the pH of glucose solutions is altered from 3.0 to 3.6. This pH change has been prescribed in the 1971 corrections to Pharmacopoea Nordica 1963. By complete neutralization of 5% glucose a further reduction of the damage to the veins has been obtained. For this purpose phosphate buffer is recommended."}
{"id": "PMID:9291", "title": "Cardiovascular response to exercise under increasing doses of chlorthalidone.", "content": "Five male subjects with essential hypertension received chlorthalidone at each of four dose levels (25, 50, 100, and 200 mg/day) for eight week periods each preceded by an eight week placebo period. Dosage order was randomized and double-blind. During the last week of each active and placebo period an upright bicycle exercise study was carried out at three loads (100, 200, 300 kpm/min) for 6 min each. Oxygen consumption at the maximal workload was 42% of predicted at a heart rate of 170. During placebo therapy, increasing workloads were associated with a progressive increase in blood pressure, heart rate, and pressure-rate index (systolic pressure times heart rate). With increasing doses of chlorthalidone up to 100 mg/day, there was a progressive reduction in blood pressure and pressure-rate index. At 200 mg/day there were paradoxical increases in diastolic pressures, heart rates and pressure-rate indices above values observed at 100 mg/day. With increasing doses of chlorthalidone, there was a progressive increase in arterial blood CO2 content and pH. Increasing workloads were associated with increased arterial blood lactate and decreased arterial blood lactate and decreased arterial blood pH. The changes in lactate and pH were not different at the different dose levels. The best antihypertensive effect in these exercising subjects was observed at a daily dose of 100 mg of chlorthalidone. The exercise response was useful in the determination of potentially adverse hemodynamic consequences of the larger dose of chlorthalidone.", "contents": "Cardiovascular response to exercise under increasing doses of chlorthalidone. Five male subjects with essential hypertension received chlorthalidone at each of four dose levels (25, 50, 100, and 200 mg/day) for eight week periods each preceded by an eight week placebo period. Dosage order was randomized and double-blind. During the last week of each active and placebo period an upright bicycle exercise study was carried out at three loads (100, 200, 300 kpm/min) for 6 min each. Oxygen consumption at the maximal workload was 42% of predicted at a heart rate of 170. During placebo therapy, increasing workloads were associated with a progressive increase in blood pressure, heart rate, and pressure-rate index (systolic pressure times heart rate). With increasing doses of chlorthalidone up to 100 mg/day, there was a progressive reduction in blood pressure and pressure-rate index. At 200 mg/day there were paradoxical increases in diastolic pressures, heart rates and pressure-rate indices above values observed at 100 mg/day. With increasing doses of chlorthalidone, there was a progressive increase in arterial blood CO2 content and pH. Increasing workloads were associated with increased arterial blood lactate and decreased arterial blood lactate and decreased arterial blood pH. The changes in lactate and pH were not different at the different dose levels. The best antihypertensive effect in these exercising subjects was observed at a daily dose of 100 mg of chlorthalidone. The exercise response was useful in the determination of potentially adverse hemodynamic consequences of the larger dose of chlorthalidone."}
{"id": "PMID:9292", "title": "Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. I. Relationship between plasma concentration and adrenergic beta-receptor blockade.", "content": "Mean steady-state plasma concentrations of alprenolol were studied in relationship to the degree of beta-blockade, in sixteen patients receiving 600 mg daily in divided doses. Steady-state alprenolol concentrations were determined from the area under the plasma concentration-time curve during one eight-hour dosage interval after treatment for six weeks. Beta-blockade during alprenolol treatment was assessed from the chronotropic response to intravenous isoprenaline compared to the response after six weeks of placebo therapy. Although there was interindividual variability in the mean steady-state alprenolol concentration (range 11 - 141 ng/ml), and in the degree of beta-blockade (7-fold), the correlation between the two variables was highly significant (r = 0.80, p less than 0.001). The prescribed dose of alprenolol (mg/kg) was not significantly correlated with the plasma level of alprenolol or the beta-blockade. The chronotropic effects of isoprenaline during placebo and alprenolol were significantly interrelated (r = 0.79, p less than 0.001).", "contents": "Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. I. Relationship between plasma concentration and adrenergic beta-receptor blockade. Mean steady-state plasma concentrations of alprenolol were studied in relationship to the degree of beta-blockade, in sixteen patients receiving 600 mg daily in divided doses. Steady-state alprenolol concentrations were determined from the area under the plasma concentration-time curve during one eight-hour dosage interval after treatment for six weeks. Beta-blockade during alprenolol treatment was assessed from the chronotropic response to intravenous isoprenaline compared to the response after six weeks of placebo therapy. Although there was interindividual variability in the mean steady-state alprenolol concentration (range 11 - 141 ng/ml), and in the degree of beta-blockade (7-fold), the correlation between the two variables was highly significant (r = 0.80, p less than 0.001). The prescribed dose of alprenolol (mg/kg) was not significantly correlated with the plasma level of alprenolol or the beta-blockade. The chronotropic effects of isoprenaline during placebo and alprenolol were significantly interrelated (r = 0.79, p less than 0.001)."}
{"id": "PMID:9293", "title": "The cardiovascular effects of etilefrine.", "content": "Intravenous etilefrine increases the pulse rate, cardiac output, stroke volume, central venous pressure and mean arterial pressure of healthy individuals. Peripheral vascular resistance falls during the infusion of 1-8 mg etilefrine but begins to rise at higher dosage. Marked falls in pulse rate, cardiac output, stroke volume and peripheral bloodflow, accompanied by rises in mean arterial pressure, occur when etilefrine is infused after administration of intravenous propranolol 2,5 mg. These findings indicate that etilefrine has both beta 1 and alpha adrenergic effects in man.", "contents": "The cardiovascular effects of etilefrine. Intravenous etilefrine increases the pulse rate, cardiac output, stroke volume, central venous pressure and mean arterial pressure of healthy individuals. Peripheral vascular resistance falls during the infusion of 1-8 mg etilefrine but begins to rise at higher dosage. Marked falls in pulse rate, cardiac output, stroke volume and peripheral bloodflow, accompanied by rises in mean arterial pressure, occur when etilefrine is infused after administration of intravenous propranolol 2,5 mg. These findings indicate that etilefrine has both beta 1 and alpha adrenergic effects in man."}
{"id": "PMID:9294", "title": "In vitro stability of proscillaridin A.", "content": "In an in vitro study, proscillardin A was found to be rapidly inactivated at low pH. More than 50 per cent of its activity, measured by 86Rb assay, was lost after incubation for 15 minutes at pH 1 and 37 degrees C. Compared with proscillaridin, the rate of inactivation of digoxin was lower in these experiments. The rapid inactivation of proscillaridin might be of clinical importance when treating patients with this glycoside.", "contents": "In vitro stability of proscillaridin A. In an in vitro study, proscillardin A was found to be rapidly inactivated at low pH. More than 50 per cent of its activity, measured by 86Rb assay, was lost after incubation for 15 minutes at pH 1 and 37 degrees C. Compared with proscillaridin, the rate of inactivation of digoxin was lower in these experiments. The rapid inactivation of proscillaridin might be of clinical importance when treating patients with this glycoside."}
{"id": "PMID:9295", "title": "Double-blind cross-over comparison of clenbuterol and salbutamol tablets in asthmatic out-patients.", "content": "A double-blind cross-over comparison of a new beta2-sympathomimetic bronchodilator, clenbuterol, with salbutamol and placebo has been made during a 24 day period of out-patient treatment of 19 adults with moderately severe asthma. Oral clenbuterol (10 mug 3 times a day) and salbutamol (4 mg 3 times a day) were equally and significantly (p less than 0.001) more effective than placebo, when daily records of peak expiratory flow or use of isoprenaline inhalations were the criteria of activity. Daily records of symptoms according to a questionnaire also suggested relief of the subjective effects of asthma during treatment with both active drugs (p less than 0.01).", "contents": "Double-blind cross-over comparison of clenbuterol and salbutamol tablets in asthmatic out-patients. A double-blind cross-over comparison of a new beta2-sympathomimetic bronchodilator, clenbuterol, with salbutamol and placebo has been made during a 24 day period of out-patient treatment of 19 adults with moderately severe asthma. Oral clenbuterol (10 mug 3 times a day) and salbutamol (4 mg 3 times a day) were equally and significantly (p less than 0.001) more effective than placebo, when daily records of peak expiratory flow or use of isoprenaline inhalations were the criteria of activity. Daily records of symptoms according to a questionnaire also suggested relief of the subjective effects of asthma during treatment with both active drugs (p less than 0.01)."}
{"id": "PMID:9296", "title": "Effects of dixyrazine and methaqualone on the sleep pattern in normal man.", "content": "Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone.", "contents": "Effects of dixyrazine and methaqualone on the sleep pattern in normal man. Whole night EEG and polygraphic recordings were made in ten young, healthy, male volunteers after dixyrazine (12.5 mg, 25 mg, 50 mg), methaqualone (250 mg) and Isonox (methaqualone 250 mg + etodroxizine 50 mg). A total of 156 recording nights (36 adaptation nights were not included in the analyses) were scored for different sleep stages according to accepted criteria. The smallest dose of dixyrazine (12.5 mg) had no significant effect upon sleep pattern: the larger doses (25 mg and 50 mg) caused significant decreases in REM-sleep during the first nights of administration. The decrease disappeared during the following two nights of treatment. No withdrawal effects were seen. Methaqualone also caused moderate depression of REM-sleep during the first night of treatment, and this effect, too, disappeared during prolonged administration. Isonox (methaqualone + etodroxizine) had a somewhat stronger surpressive effect upon REM-sleep than methaqualone alone."}
{"id": "PMID:9297", "title": "Evaluation of in vivo parameters of drug metabolizing enzyme activity in man after administration of clemastine, phenobarbital or placebo.", "content": "The 24 h urinary excretion of 6beta-hydroxycortisol and D-glucaric acid, the plasma half lives and total clearances of aminopyrine, and serum gamma-glutamyl-transpeptidase activity have been measured in nineteen healthy male volunteers. The study was done double blind and was conducted as a test of induction of microsomal drug metabolizing enzymes during and after daily doses of 6 mg clemastine, 300 mg phenobarbital or a placebo. The urinary excretion of 6beta-hydroxycortisol and D-glucaric acid was significantly increased in the phenobarbital group, the standard for induction. No changes were observed after treatment with clemastine or placebo. Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo. Gamma-glutamyl-transpeptidase activity increased only in the phenobarbital group. The elimination constant k2 of aminopyrine and the excretion of glucaric acid in the pre-medication period were correlated (p less than 0.05) The results indicate that the tests  were of diagnostic value in determination of microsomal enzyme induction by phenobarbital. Failure to observe similar changes after treatment with clemastine imply failure of induction of this activity under the experimental conditions.", "contents": "Evaluation of in vivo parameters of drug metabolizing enzyme activity in man after administration of clemastine, phenobarbital or placebo. The 24 h urinary excretion of 6beta-hydroxycortisol and D-glucaric acid, the plasma half lives and total clearances of aminopyrine, and serum gamma-glutamyl-transpeptidase activity have been measured in nineteen healthy male volunteers. The study was done double blind and was conducted as a test of induction of microsomal drug metabolizing enzymes during and after daily doses of 6 mg clemastine, 300 mg phenobarbital or a placebo. The urinary excretion of 6beta-hydroxycortisol and D-glucaric acid was significantly increased in the phenobarbital group, the standard for induction. No changes were observed after treatment with clemastine or placebo. Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo. Gamma-glutamyl-transpeptidase activity increased only in the phenobarbital group. The elimination constant k2 of aminopyrine and the excretion of glucaric acid in the pre-medication period were correlated (p less than 0.05) The results indicate that the tests  were of diagnostic value in determination of microsomal enzyme induction by phenobarbital. Failure to observe similar changes after treatment with clemastine imply failure of induction of this activity under the experimental conditions."}
{"id": "PMID:9298", "title": "Long term treatment of moderate hypertension with penbutolol (Hoe 893d). I. Effects on blood pressure, pulse rate, catecholamines in blood and urine, plasma renin activity and urinary aldosterone under basal conditions and following exercise.", "content": "The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2-4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3-8 months) 4-60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2-4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20-30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.", "contents": "Long term treatment of moderate hypertension with penbutolol (Hoe 893d). I. Effects on blood pressure, pulse rate, catecholamines in blood and urine, plasma renin activity and urinary aldosterone under basal conditions and following exercise. The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2-4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3-8 months) 4-60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2-4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20-30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated."}
{"id": "PMID:9299", "title": "Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration to man.", "content": "A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 - 5.0 mug/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 - 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 - 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug.", "contents": "Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration to man. A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 - 5.0 mug/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 - 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 - 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug."}
{"id": "PMID:9300", "title": "The physiological disposition of etilefrine in man.", "content": "Pharmacokinetic and metabolic studies with 3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of 3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, beta) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.", "contents": "The physiological disposition of etilefrine in man. Pharmacokinetic and metabolic studies with 3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of 3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, beta) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated."}
{"id": "PMID:9301", "title": "Long term treatment of moderate hypertension with penbutolol (Hoe 893d). II. Effect on the response of plasma catecholamines and plasma renin activity to insulin-induced hypoglycemia.", "content": "The effect of insulin-induced hypoglycemia on the blood levels of catecholamines and renin activity has been studied in five patients with moderate hypertension before and after treatment for 3 - 8 months with penbutolol (PEN) 20 - 30 mg twice daily. Penbutolol caused no change in fasting blood glucose level. Insulin o.1 IU per kg body weight i.v. reduced blood glucose concentration by approximately 50 per cent after 30 - 45 min, both before and during treatment with penbutolol. Hypoglycemia prior to medication was accompanied by a marked increase in the production of adrenaline and a minor increase of noradrenaline in all five patients. During treatment the response of adrenaline to hypoglycemia was reduced in four patients and the data was inconclusive in one. Basal renin activity was rather low in three patients, within the normal range in one and relatively high in one. Before penbutolol the hypoglycemia-induced increase in catecholamine production caused no change in plasma renin activity in the three patients with low basal levels, whereas a marked increase was observed in the other two. During medication plasma renin activity remained unchanged on induction of hypoglycemia regardless of the catecholamine response. Despite the marked increase in plasma adrenaline following insulin-induced hypoglycemia, no statistically significant increase in pulse rate was recorded.", "contents": "Long term treatment of moderate hypertension with penbutolol (Hoe 893d). II. Effect on the response of plasma catecholamines and plasma renin activity to insulin-induced hypoglycemia. The effect of insulin-induced hypoglycemia on the blood levels of catecholamines and renin activity has been studied in five patients with moderate hypertension before and after treatment for 3 - 8 months with penbutolol (PEN) 20 - 30 mg twice daily. Penbutolol caused no change in fasting blood glucose level. Insulin o.1 IU per kg body weight i.v. reduced blood glucose concentration by approximately 50 per cent after 30 - 45 min, both before and during treatment with penbutolol. Hypoglycemia prior to medication was accompanied by a marked increase in the production of adrenaline and a minor increase of noradrenaline in all five patients. During treatment the response of adrenaline to hypoglycemia was reduced in four patients and the data was inconclusive in one. Basal renin activity was rather low in three patients, within the normal range in one and relatively high in one. Before penbutolol the hypoglycemia-induced increase in catecholamine production caused no change in plasma renin activity in the three patients with low basal levels, whereas a marked increase was observed in the other two. During medication plasma renin activity remained unchanged on induction of hypoglycemia regardless of the catecholamine response. Despite the marked increase in plasma adrenaline following insulin-induced hypoglycemia, no statistically significant increase in pulse rate was recorded."}
{"id": "PMID:9302", "title": "Gastrointestinal absorption and metabolism of two 35S-labelled ampicillin esters.", "content": "Two ampicillin esters, 35S-pivampicillin and 35S-carampicillin and polyethylene glycol (nonabsorbable marker) were given orally to healthy subjects with gastrointestinal tubes. The cumulative absorption of radioactivity in both compounds (60-90%) was higher than (25-67%) previously found after administration of 35S-ampicillin. The pek plasma levels of radioactivity were reached earlier and were about twice as high as in the latter study. The amount of radioactivity excreted in urine was about the same as that absorbed from the proximal part of the gastrointestinal tract. Both 35S-pivampicillin and 35S-carampicillin were partly hydrolyzed in the stomach and upper small intestine and labelled ampicillin was released. They were also decomposed after absorption since all the radioactivity recovered from blood and urine appeared to be attached to ampicillin and ampicillin metabolites. Studies in vitro indicated that ampicillin esters absorbed intact may be hydrolyzed not only in the blood but also in the intestinal wall and the liver.", "contents": "Gastrointestinal absorption and metabolism of two 35S-labelled ampicillin esters. Two ampicillin esters, 35S-pivampicillin and 35S-carampicillin and polyethylene glycol (nonabsorbable marker) were given orally to healthy subjects with gastrointestinal tubes. The cumulative absorption of radioactivity in both compounds (60-90%) was higher than (25-67%) previously found after administration of 35S-ampicillin. The pek plasma levels of radioactivity were reached earlier and were about twice as high as in the latter study. The amount of radioactivity excreted in urine was about the same as that absorbed from the proximal part of the gastrointestinal tract. Both 35S-pivampicillin and 35S-carampicillin were partly hydrolyzed in the stomach and upper small intestine and labelled ampicillin was released. They were also decomposed after absorption since all the radioactivity recovered from blood and urine appeared to be attached to ampicillin and ampicillin metabolites. Studies in vitro indicated that ampicillin esters absorbed intact may be hydrolyzed not only in the blood but also in the intestinal wall and the liver."}
{"id": "PMID:9303", "title": "Brain homovanillic acid: regional changes over time with antipsychotic drugs.", "content": "Acute administration of equivalent doses of either chlorpromazine, thioridazine, or clozapine, respectively, produced progressively smaller increases in brain homovanillic acid (HVA) in the rabbit; however, changes in HVA in three brain regions were of equal magnitude for a single dose of a given drug. Chronic administration of fluphenazine enanthate resulted in a decrease in HVA relative to acute treatment in caudate more than limbic regions. No differences between caudate and limbic regions were observed during daily chlorpromazine administration for 3 ro 8 days. Tolerance appeared to develop in approximately 1 week. Chronic treatment with clozapine produced no tolerance at one week but suggestive evidence of tolerance in caudate and limbic regions at two weeks. No tolerance was observed in the hypothalamus during chronic treatment with any drug used. Cisternal CSF HVA paralleled caudate HVA during acute and chronic treatments.", "contents": "Brain homovanillic acid: regional changes over time with antipsychotic drugs. Acute administration of equivalent doses of either chlorpromazine, thioridazine, or clozapine, respectively, produced progressively smaller increases in brain homovanillic acid (HVA) in the rabbit; however, changes in HVA in three brain regions were of equal magnitude for a single dose of a given drug. Chronic administration of fluphenazine enanthate resulted in a decrease in HVA relative to acute treatment in caudate more than limbic regions. No differences between caudate and limbic regions were observed during daily chlorpromazine administration for 3 ro 8 days. Tolerance appeared to develop in approximately 1 week. Chronic treatment with clozapine produced no tolerance at one week but suggestive evidence of tolerance in caudate and limbic regions at two weeks. No tolerance was observed in the hypothalamus during chronic treatment with any drug used. Cisternal CSF HVA paralleled caudate HVA during acute and chronic treatments."}
{"id": "PMID:9309", "title": "Hypoxia in fibroblast cultures. I. Changes in glucose consumption by 5 vol.-% oxygen concentration and reduced pH.", "content": "In secondary cultures of rat embryonic fibroblasts the glucose consumption and lactate concentration were comparatively investigated in 5 and 21 Vol.-% O2 environment at pH 6.6 and pH 7.4 (HEPES-buffer). The results were correlated with cell density. The following observations were made: 1. At pH 6.6 the rate of cell proliferation was reduced to 81%; by additional hypoxia it was reduced to 71%. 2. Increase in cell density effectuated decrease of glucose consumption and lactate production at pH 7.4 and pH 6.6 in 5% as well as in 21% O2 environment. 3. At pH 7.4 enhancement of glucose consumption and lactate production due to hypoxia can be observed only at low cell density. 4. At pH 6.6 respiration of fibroblasts was little influenced by 5% O2 environment. 5. Transition from pH 7.4/21% O2 to pH 6.6/5% O2 effectuated decrease in glucose consumption and lactate concentration in tissues in hypoxic environment. This suggests a pH-governed feedback mechanism. Abbreviations used in the text: c-AMP = cyclic adenosine monophosphate; MPS = acid mucopolysaccharides (glycosaminoglycans).", "contents": "Hypoxia in fibroblast cultures. I. Changes in glucose consumption by 5 vol.-% oxygen concentration and reduced pH. In secondary cultures of rat embryonic fibroblasts the glucose consumption and lactate concentration were comparatively investigated in 5 and 21 Vol.-% O2 environment at pH 6.6 and pH 7.4 (HEPES-buffer). The results were correlated with cell density. The following observations were made: 1. At pH 6.6 the rate of cell proliferation was reduced to 81%; by additional hypoxia it was reduced to 71%. 2. Increase in cell density effectuated decrease of glucose consumption and lactate production at pH 7.4 and pH 6.6 in 5% as well as in 21% O2 environment. 3. At pH 7.4 enhancement of glucose consumption and lactate production due to hypoxia can be observed only at low cell density. 4. At pH 6.6 respiration of fibroblasts was little influenced by 5% O2 environment. 5. Transition from pH 7.4/21% O2 to pH 6.6/5% O2 effectuated decrease in glucose consumption and lactate concentration in tissues in hypoxic environment. This suggests a pH-governed feedback mechanism. Abbreviations used in the text: c-AMP = cyclic adenosine monophosphate; MPS = acid mucopolysaccharides (glycosaminoglycans)."}
{"id": "PMID:9310", "title": "Hypoxia in fibroblast cultures. 2. Influence of pH on the distribution pattern of acid mucopolysaccharides.", "content": "Secondary cultures of embryonic rat fibroblasts [NEUPERT et al., Exp. Path. 7, 19-28 (1972)] were cultured in 21% and 5% O2 concentration at pH 6.6 and 7.4 for 6 or 8 days. The acid mucopolysaccharides were isolated and fractionated by alcohol precipitation, papain digestion, CPC-precipitation and fractionation after the microtechniques of SVEJCAR and ROBERTSON [see KITTLICK and NEUPERT, Exp. Path. 7, 7-18 (1972)]. Cells and medium were investigated together. The results were related to cell density and compared with the glucose and lactate values [see KITTLICK and NEUPERT, Exp. Path. 10, 109-114 (1975)]. Concerning the question of interrelations of MPS-synthesis and glycolysis a survey on literature is given. Our own test results were as follows: 1. Hypoxia (5% O2) did not influence MPS-total synthesis. 2. Depending on cell density the individual MPS fractions were different in their reaction to hypoxia. 3. Hyaluronic acid (and heparan sulphate) in the MPS-pattern showed other behaviour than chondroitin sulphate and dermatan sulphate, respectively. 4. At low cell density hypoxia effectuated increase in hyaluronic acid and decrease in chondroitin sulphate and dermatan sulphate, respectively. 5. At high cell density hypoxia effectuated decrease in hyaluronic acid and increase in chondroitin sulphate and dermatan sulphate, respectively. Possible relationship to processes in the tissue is discussed.", "contents": "Hypoxia in fibroblast cultures. 2. Influence of pH on the distribution pattern of acid mucopolysaccharides. Secondary cultures of embryonic rat fibroblasts [NEUPERT et al., Exp. Path. 7, 19-28 (1972)] were cultured in 21% and 5% O2 concentration at pH 6.6 and 7.4 for 6 or 8 days. The acid mucopolysaccharides were isolated and fractionated by alcohol precipitation, papain digestion, CPC-precipitation and fractionation after the microtechniques of SVEJCAR and ROBERTSON [see KITTLICK and NEUPERT, Exp. Path. 7, 7-18 (1972)]. Cells and medium were investigated together. The results were related to cell density and compared with the glucose and lactate values [see KITTLICK and NEUPERT, Exp. Path. 10, 109-114 (1975)]. Concerning the question of interrelations of MPS-synthesis and glycolysis a survey on literature is given. Our own test results were as follows: 1. Hypoxia (5% O2) did not influence MPS-total synthesis. 2. Depending on cell density the individual MPS fractions were different in their reaction to hypoxia. 3. Hyaluronic acid (and heparan sulphate) in the MPS-pattern showed other behaviour than chondroitin sulphate and dermatan sulphate, respectively. 4. At low cell density hypoxia effectuated increase in hyaluronic acid and decrease in chondroitin sulphate and dermatan sulphate, respectively. 5. At high cell density hypoxia effectuated decrease in hyaluronic acid and increase in chondroitin sulphate and dermatan sulphate, respectively. Possible relationship to processes in the tissue is discussed."}
{"id": "PMID:9311", "title": "The extracellular protease from Pseudomonas fluorescens.", "content": "An extracellular protease has been purified from cultures of Pseudomonas fluorescens. It is a metalloenzyme with a molecular weight of 37,000 +/- 3,700, able to digest casein, hemoglobin and gelatine.", "contents": "The extracellular protease from Pseudomonas fluorescens. An extracellular protease has been purified from cultures of Pseudomonas fluorescens. It is a metalloenzyme with a molecular weight of 37,000 +/- 3,700, able to digest casein, hemoglobin and gelatine."}
{"id": "PMID:9312", "title": "Anionic activation of human salivary amylase.", "content": "In all earlier studies on alpha-amylase, the influence of different ions were studied in phosphate buffer. The present report shows the effect of different ions individually with Tris and amino acid. Though it has been claimed recently that sodium ion is an activator of alpha-amylase, this study reconfirms that sodium ion does not activate human salivary amylase.", "contents": "Anionic activation of human salivary amylase. In all earlier studies on alpha-amylase, the influence of different ions were studied in phosphate buffer. The present report shows the effect of different ions individually with Tris and amino acid. Though it has been claimed recently that sodium ion is an activator of alpha-amylase, this study reconfirms that sodium ion does not activate human salivary amylase."}
{"id": "PMID:9313", "title": "Effect of benzimidazole on nicotinamide adenine dinucleotide phosphate phosphomonoesterase activity in wheat leaves.", "content": "Nicotinamide adenine dinucleotide phosphate phosphomonoesterase was isolated and partially purified from wheat (Triticum aestivum L. var. Selkirk) leaves. The enzyme had KNADP value of 1.4 X 10(-4) M and a pH optimum of 5.9. In vitro activity of this enzyme was unaffected by precursors of NAD (nicotinamide and nicotinic acid) or cytokinins (kinetin and benzimidazole). However, when detached wheat leaves were treated with solutions of these compounds, the precursors lowered the specific activity while the cytokinins enhanced the activity. It is suggested that spatial separation and compartmentation of the enzyme and its substrate NADP account for the similar effect of benzimidazole on both.", "contents": "Effect of benzimidazole on nicotinamide adenine dinucleotide phosphate phosphomonoesterase activity in wheat leaves. Nicotinamide adenine dinucleotide phosphate phosphomonoesterase was isolated and partially purified from wheat (Triticum aestivum L. var. Selkirk) leaves. The enzyme had KNADP value of 1.4 X 10(-4) M and a pH optimum of 5.9. In vitro activity of this enzyme was unaffected by precursors of NAD (nicotinamide and nicotinic acid) or cytokinins (kinetin and benzimidazole). However, when detached wheat leaves were treated with solutions of these compounds, the precursors lowered the specific activity while the cytokinins enhanced the activity. It is suggested that spatial separation and compartmentation of the enzyme and its substrate NADP account for the similar effect of benzimidazole on both."}
{"id": "PMID:9314", "title": "Gastric mucus effusion elicited by oral copper compounds: potential anti-ulcer activity.", "content": "In rats, both Cu(I) and Cu(II) show an irritancy profile not shared with Cu degrees or Zn(II) or Ni(II). The gastric response to Cu(II), i.e. copius fluid and mucus secretion, can protect the stomach from the acute ulcerative effects of aspirin or physical stress administered subsequently.", "contents": "Gastric mucus effusion elicited by oral copper compounds: potential anti-ulcer activity. In rats, both Cu(I) and Cu(II) show an irritancy profile not shared with Cu degrees or Zn(II) or Ni(II). The gastric response to Cu(II), i.e. copius fluid and mucus secretion, can protect the stomach from the acute ulcerative effects of aspirin or physical stress administered subsequently."}
{"id": "PMID:9318", "title": "The effect of ion-exchange column chromatography on separation of X and Y chromosome-bearing human spermatozoa.", "content": "Separation of X and Y chromosome-bearing spermatozoa has been attempted using ion-exchange column chromatography, with cation- and anion-exchange resins of low, intermediate, and high ionic strength. Examination of F-bodies on the Y chromosome of treated human sperm and progeny resulting from insemination of treated rabbit spermatozoa indicates that in none of the cases investigated did the treatment cause a separation of X and Y chromosome-bearing spermatozoa. The treatment does appear to filter out dead rabbit (and bull) spermatozoa, but the possible beneficial effects of this phenomenon are as yet uninvestigated.", "contents": "The effect of ion-exchange column chromatography on separation of X and Y chromosome-bearing human spermatozoa. Separation of X and Y chromosome-bearing spermatozoa has been attempted using ion-exchange column chromatography, with cation- and anion-exchange resins of low, intermediate, and high ionic strength. Examination of F-bodies on the Y chromosome of treated human sperm and progeny resulting from insemination of treated rabbit spermatozoa indicates that in none of the cases investigated did the treatment cause a separation of X and Y chromosome-bearing spermatozoa. The treatment does appear to filter out dead rabbit (and bull) spermatozoa, but the possible beneficial effects of this phenomenon are as yet uninvestigated."}
{"id": "PMID:9319", "title": "Equality in survival of X and Y chromosome-bearing human spermatozoa.", "content": "Human X and Y chromosome-bearing spermatozoa survived equally well during washing and resuspension in buffers of pH 5.2 and 8.0 and during incubation in these buffers for 11 hours at 37 degrees C. This suggests that alteration of the ratio of living X- and Y-bearing spermatozoa by direct treatment is not an effective method of sex ratio alteration.", "contents": "Equality in survival of X and Y chromosome-bearing human spermatozoa. Human X and Y chromosome-bearing spermatozoa survived equally well during washing and resuspension in buffers of pH 5.2 and 8.0 and during incubation in these buffers for 11 hours at 37 degrees C. This suggests that alteration of the ratio of living X- and Y-bearing spermatozoa by direct treatment is not an effective method of sex ratio alteration."}
{"id": "PMID:9320", "title": "Accumulation of nicotine in the uterine fluid of the six-day pregnant rabbit.", "content": "In 6-day pregnant New Zealand White rabbits dosed intravenously with 3H-nicotine, the 3H-activity in the uterine fluid was approximately 5 to 11 times greater than that in the plasma at the corresponding times; 3H-nicotine itself accounted for most of this radioactivity. Dichlorodiphenyltrichloroethane (DDT) also accumulated in the uterine luminal fluid of 6-day pregnant rabbits, but to a lesser extent. However, nicotine or DDT accumulation did not occur in similarly treated, nonpregnant rabbits. The radioactivity in the uterine fluid of rabbits treated with 14C-isoniazid, salicylic acid, barbital, antipyrine, and caffeine was not different from that in the plasma (uterine fluid to plasma radioactivity ratios ranged between 0.67 and 1.85) in both 6-day pregnant and nonpregnant rabbits. No differences in regard to nicotine metabolism, volume of distribution, plasma disappearance, plasma protein binding, or urinary excretion were found between 6-day pregnant and nonpregnant rabbits. Accumulation of nicotine took place in the uterine luminal fluid of nonpregnant does pretreated with either progesterone or human chorionic gonadotropin, but did not occur in does pretreated with estrogen. It is possible that the accumulation of nicotine in uterine fluid of pregnant does and in human chorionic gonadotropin- or progesterone-pretreated nonpregnant does is due to the binding of nicotine to specific uterine fluid proteins.", "contents": "Accumulation of nicotine in the uterine fluid of the six-day pregnant rabbit. In 6-day pregnant New Zealand White rabbits dosed intravenously with 3H-nicotine, the 3H-activity in the uterine fluid was approximately 5 to 11 times greater than that in the plasma at the corresponding times; 3H-nicotine itself accounted for most of this radioactivity. Dichlorodiphenyltrichloroethane (DDT) also accumulated in the uterine luminal fluid of 6-day pregnant rabbits, but to a lesser extent. However, nicotine or DDT accumulation did not occur in similarly treated, nonpregnant rabbits. The radioactivity in the uterine fluid of rabbits treated with 14C-isoniazid, salicylic acid, barbital, antipyrine, and caffeine was not different from that in the plasma (uterine fluid to plasma radioactivity ratios ranged between 0.67 and 1.85) in both 6-day pregnant and nonpregnant rabbits. No differences in regard to nicotine metabolism, volume of distribution, plasma disappearance, plasma protein binding, or urinary excretion were found between 6-day pregnant and nonpregnant rabbits. Accumulation of nicotine took place in the uterine luminal fluid of nonpregnant does pretreated with either progesterone or human chorionic gonadotropin, but did not occur in does pretreated with estrogen. It is possible that the accumulation of nicotine in uterine fluid of pregnant does and in human chorionic gonadotropin- or progesterone-pretreated nonpregnant does is due to the binding of nicotine to specific uterine fluid proteins."}
{"id": "PMID:9322", "title": "Oxygen transport impairment in diabetes.", "content": "Oxyhemoglobin dissociation curves (ODC) from zero to full saturation were developed from tests performed on whole blood from various groups of diabetic and nondiabetic healthy subjects. P50 at in-vivo pH was slightly but significantly lower than normal in ambulatory nonacidotic, uncomplicated juvenile diabetics (26.0 vs. 27.3 mm. Hg, P less than 0.001), despite increased red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations in diabetic erythrocytes (15.0 vs. 13.7 mumole/gm. Hb, P less than 0.001). This combination of changes is in keeping with the presence of increased proportions of hemoglobin AIc in insulin-treated diabetics. The position of the ODC was positively correlated with the 2,3-DPG concentration (P less than 0.01), which varied in response to fluctuations in plasma concentration of inorganic phosphate (Pi) (P less than 0.001). Optimal metabolic control may lead to a normalization of the ODC in association with increased concentrations of red cell 2,3-DPG and P. When the diabetes was uncontrolled, the ODC was usually unchanged during the acidotic phase because the lowered pH balanced the effect of diminished 2,3-DPG concentration on the ODC. After correction of acidosis, the disproportion between erythrocyte 2,3-DPG and pH became quite prominent, accompanied by a corresponding fall in P50 (21.0 vs. 26.1 mm. Hg, P less than 0.001). Following ketoacidosis, with a persistently lowered Pi, it may take up to one week for 2,3-DPG to return to an approximately normal level, and the P50 will be impaired for the same period. A diphosphonate (EHDP) known to enhance tubular phosphate reabsorption in man was given to nonacidotic insulin-treated diabetic and healthy volunteers for 28 days. It caused a significant increase in mean Pi and P50 in both healthy and diabetic subjects (r = 0.58, P less than 0.01). When a dietary supplement of dibasic calcium phosphate was given to diabetic subjects for 28 days, a significant increase in P50 also occurred (25.2 vs. 27.2 mm. Hg, P less than 0.001). It is recommended that the diabetes diet be supplemented by dibasic calcium phosphate to prevent the inhibitory effect of a low concentration of Pi on red cell oxygen delivery.", "contents": "Oxygen transport impairment in diabetes. Oxyhemoglobin dissociation curves (ODC) from zero to full saturation were developed from tests performed on whole blood from various groups of diabetic and nondiabetic healthy subjects. P50 at in-vivo pH was slightly but significantly lower than normal in ambulatory nonacidotic, uncomplicated juvenile diabetics (26.0 vs. 27.3 mm. Hg, P less than 0.001), despite increased red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations in diabetic erythrocytes (15.0 vs. 13.7 mumole/gm. Hb, P less than 0.001). This combination of changes is in keeping with the presence of increased proportions of hemoglobin AIc in insulin-treated diabetics. The position of the ODC was positively correlated with the 2,3-DPG concentration (P less than 0.01), which varied in response to fluctuations in plasma concentration of inorganic phosphate (Pi) (P less than 0.001). Optimal metabolic control may lead to a normalization of the ODC in association with increased concentrations of red cell 2,3-DPG and P. When the diabetes was uncontrolled, the ODC was usually unchanged during the acidotic phase because the lowered pH balanced the effect of diminished 2,3-DPG concentration on the ODC. After correction of acidosis, the disproportion between erythrocyte 2,3-DPG and pH became quite prominent, accompanied by a corresponding fall in P50 (21.0 vs. 26.1 mm. Hg, P less than 0.001). Following ketoacidosis, with a persistently lowered Pi, it may take up to one week for 2,3-DPG to return to an approximately normal level, and the P50 will be impaired for the same period. A diphosphonate (EHDP) known to enhance tubular phosphate reabsorption in man was given to nonacidotic insulin-treated diabetic and healthy volunteers for 28 days. It caused a significant increase in mean Pi and P50 in both healthy and diabetic subjects (r = 0.58, P less than 0.01). When a dietary supplement of dibasic calcium phosphate was given to diabetic subjects for 28 days, a significant increase in P50 also occurred (25.2 vs. 27.2 mm. Hg, P less than 0.001). It is recommended that the diabetes diet be supplemented by dibasic calcium phosphate to prevent the inhibitory effect of a low concentration of Pi on red cell oxygen delivery."}
{"id": "PMID:9323", "title": "Increased microvascular permeability to plasma proteins in short- and long-term juvenile diabetics.", "content": "The present findings of increased microvascular protein passage are compatible with the hypothesis that the organic, histologically demonstrated diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i.e., the concept of plasmatic vasculosis. Arterial hypertension, frequently present in diabetes, enhances the development of arteriolar hyalinosis. Effective treatment of diabetes and hypertension arrests development of the microvascular lesions.", "contents": "Increased microvascular permeability to plasma proteins in short- and long-term juvenile diabetics. The present findings of increased microvascular protein passage are compatible with the hypothesis that the organic, histologically demonstrated diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i.e., the concept of plasmatic vasculosis. Arterial hypertension, frequently present in diabetes, enhances the development of arteriolar hyalinosis. Effective treatment of diabetes and hypertension arrests development of the microvascular lesions."}
{"id": "PMID:9324", "title": "Muscle metabolism during rest and exercise: influence on the oxygen transport system of blood in normal and diabetic subjects.", "content": "The oxygen dissociation curve shifted less to the right in venous blood draining from muscle in eight insulin-deficient diabetics working at a constant submaximal workload than in seven normal controls (28.7 mm. Hg vs. 30.8 mm Hg; P less than 0.05). This diminution of the in-vivo Bohr effect at the muscle tissue level during exercise in diabetics was due to a significantly smaller decrease of venous blood pH (down to 7.33 vs. 7.27 in normals; P less than 0.05), probably a consequence of an latered muscle metabolism in insulin deficiency. Although no glucose was taken up, even during exercise, and less lactate was produced by insulin-deficient muscle (P less than 0.05), the differences in venous blood pH appeared to be brought about mainly by a different CO2 production of the exercising muscle in the two groups. The response of Krebs cycle activity to exercise in insulin-deficient muscle might have been inadequate, as suggested by the increased 3-hydroxybutyrate/acetoacetate ratio in the venous blood observed in the normal controls but not in the diabetics. Furthermore, proportionally less of the arterial ketone body concentration was utilized by the working muscle in the insulin-deficient diabetics. Changes in erythrocyte 2,3-diphosphoglycerate did not contribute to the differences in the in-vivo Bohr effect.", "contents": "Muscle metabolism during rest and exercise: influence on the oxygen transport system of blood in normal and diabetic subjects. The oxygen dissociation curve shifted less to the right in venous blood draining from muscle in eight insulin-deficient diabetics working at a constant submaximal workload than in seven normal controls (28.7 mm. Hg vs. 30.8 mm Hg; P less than 0.05). This diminution of the in-vivo Bohr effect at the muscle tissue level during exercise in diabetics was due to a significantly smaller decrease of venous blood pH (down to 7.33 vs. 7.27 in normals; P less than 0.05), probably a consequence of an latered muscle metabolism in insulin deficiency. Although no glucose was taken up, even during exercise, and less lactate was produced by insulin-deficient muscle (P less than 0.05), the differences in venous blood pH appeared to be brought about mainly by a different CO2 production of the exercising muscle in the two groups. The response of Krebs cycle activity to exercise in insulin-deficient muscle might have been inadequate, as suggested by the increased 3-hydroxybutyrate/acetoacetate ratio in the venous blood observed in the normal controls but not in the diabetics. Furthermore, proportionally less of the arterial ketone body concentration was utilized by the working muscle in the insulin-deficient diabetics. Changes in erythrocyte 2,3-diphosphoglycerate did not contribute to the differences in the in-vivo Bohr effect."}
{"id": "PMID:9325", "title": "Effect of duodenal acidification on gastric mucus and acid secretion in conscious cats.", "content": "In cats with gastric fistulae and Heidenhein pouches, the effect of acid entering the duodenum on secretion of acid, pepsin, and mucus from the Heidenhain pouch during maximal acid stimulation with pentagastrin or histamine, was studied. Duodenal acidification produced stimulation of pepsin and mucus secretion comparable to that induced by exogenous hormones (secretin and the combination of secretin with cholecystokinin). In addition, duodenal acidification caused an increase in acid secretion, thus suggesting that, in addition to secretin and cholecystokinin, a factor that stimulates acid secretion was also released by acid.", "contents": "Effect of duodenal acidification on gastric mucus and acid secretion in conscious cats. In cats with gastric fistulae and Heidenhein pouches, the effect of acid entering the duodenum on secretion of acid, pepsin, and mucus from the Heidenhain pouch during maximal acid stimulation with pentagastrin or histamine, was studied. Duodenal acidification produced stimulation of pepsin and mucus secretion comparable to that induced by exogenous hormones (secretin and the combination of secretin with cholecystokinin). In addition, duodenal acidification caused an increase in acid secretion, thus suggesting that, in addition to secretin and cholecystokinin, a factor that stimulates acid secretion was also released by acid."}
{"id": "PMID:9327", "title": "Higher transpeptidation activity and broad acceptor specificity of gamma-glutamyltransferases of tumors.", "content": "The gamma-glutamyltransferase (EC 2.3.2.2) (=gamma-glutamyltranspeptidase, gamma-GTP) activity in hepatoma induced by 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) was 120-fold higher than that of normal liver and high activity was also found in bovine hepatocellular carcinoma. gamma-GTPs from these malignant tissues responded more and showed broader specificity to gamma-glutamyl group acceptors than those from normal tissue such as bovine, rat, and mouse liver and bovine kidney. Three species of gamma-GTP were isolated from bovine kidney by DEAE-cellulose chromatography, whereas only two species were isolated from bovine hepatocellular carcinoma. The carcinoma lacked the least acidic enzyme species. Appropriate gamma-glutamyl group acceptors stimulated more-acidic enzyme species more than less-acidic species in both tissues. The fractions separated from the hepatoma were stimulated more than those of kidney by gamma-glutamyl group acceptor. The enzymes from normal tissues responded similarly to a gamma-glutamyl group acceptor irrespective of the difference in their activity. Thus, gamma-GTPs of malignant tissues appear to be more versatile for amino acid transport, both qualitatively and quantitatively. In these properties the enzyme of mouse fetal liver which showed the highest activity in the last period of pregnancy resembled the enzymes of malignant rather than normal tissues. The activity of hepatic gamma-GTP is not parallel with the rate of cell proliferation during normal development.", "contents": "Higher transpeptidation activity and broad acceptor specificity of gamma-glutamyltransferases of tumors. The gamma-glutamyltransferase (EC 2.3.2.2) (=gamma-glutamyltranspeptidase, gamma-GTP) activity in hepatoma induced by 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) was 120-fold higher than that of normal liver and high activity was also found in bovine hepatocellular carcinoma. gamma-GTPs from these malignant tissues responded more and showed broader specificity to gamma-glutamyl group acceptors than those from normal tissue such as bovine, rat, and mouse liver and bovine kidney. Three species of gamma-GTP were isolated from bovine kidney by DEAE-cellulose chromatography, whereas only two species were isolated from bovine hepatocellular carcinoma. The carcinoma lacked the least acidic enzyme species. Appropriate gamma-glutamyl group acceptors stimulated more-acidic enzyme species more than less-acidic species in both tissues. The fractions separated from the hepatoma were stimulated more than those of kidney by gamma-glutamyl group acceptor. The enzymes from normal tissues responded similarly to a gamma-glutamyl group acceptor irrespective of the difference in their activity. Thus, gamma-GTPs of malignant tissues appear to be more versatile for amino acid transport, both qualitatively and quantitatively. In these properties the enzyme of mouse fetal liver which showed the highest activity in the last period of pregnancy resembled the enzymes of malignant rather than normal tissues. The activity of hepatic gamma-GTP is not parallel with the rate of cell proliferation during normal development."}
{"id": "PMID:9328", "title": "Ion selective effects of salicylate on antral mucosa.", "content": "The effects of luminal salicylate, 5mM, were measured on rates of ion transport by isolated antral mucosa. At neutral luminal pH, salicylate increases Na and decreases Cl permeability. Salicylate does not alter net Na transport but decreases net Cl secretion. At luminal pH 4, the effects of salicylate can be arbitrarily divided into two phases. The intitial phase is associated with an increase in Na and marked decrease in Cl permeability. Subsequently, a greater increase in Na permeability and a marked increase in Cl permeability occurs. Active Na transport persists in the presence of salicylate at pH 4. Indirect evidence also suggests that Cl secretion persists under these conditions, buy at a reduced rate. The rate of luminal acid acid loss also increases in the presence of salicylate. A 4-fold increase in salicylate concentration or decrease in luminal pH from 4 to 3 did not appear to intensify the effects observed for 5 mM salicylate at pH 4. The increase in cation and decrease in anion permeability observed at pH 7 and initially at pH 4 are compatible with an influence of a negative charge of the salicylate anion. The subsequent changes observed in the presence of acid also are compatible with the concept that as the mucosa becomes overwhelmed with acid, a nonspecific increase in permeability occurs. However, the effect of salicylate on active Cl transport is largely independent of acid diffusing into the mucosa.", "contents": "Ion selective effects of salicylate on antral mucosa. The effects of luminal salicylate, 5mM, were measured on rates of ion transport by isolated antral mucosa. At neutral luminal pH, salicylate increases Na and decreases Cl permeability. Salicylate does not alter net Na transport but decreases net Cl secretion. At luminal pH 4, the effects of salicylate can be arbitrarily divided into two phases. The intitial phase is associated with an increase in Na and marked decrease in Cl permeability. Subsequently, a greater increase in Na permeability and a marked increase in Cl permeability occurs. Active Na transport persists in the presence of salicylate at pH 4. Indirect evidence also suggests that Cl secretion persists under these conditions, buy at a reduced rate. The rate of luminal acid acid loss also increases in the presence of salicylate. A 4-fold increase in salicylate concentration or decrease in luminal pH from 4 to 3 did not appear to intensify the effects observed for 5 mM salicylate at pH 4. The increase in cation and decrease in anion permeability observed at pH 7 and initially at pH 4 are compatible with an influence of a negative charge of the salicylate anion. The subsequent changes observed in the presence of acid also are compatible with the concept that as the mucosa becomes overwhelmed with acid, a nonspecific increase in permeability occurs. However, the effect of salicylate on active Cl transport is largely independent of acid diffusing into the mucosa."}
{"id": "PMID:9329", "title": "Mechanism of prevention of aspirin-induced gastric lesions by bile duct legation in the rat.", "content": "Gastric reflux of bile has been reported to be essential for the production of acute gastric mucosal lesions by intragastric aspirin in the rat. The purpose of the present study was to determine whether bile duct legation of pylorus ligation in the rat inhibits asprin-induced gastric lesions, and, if so, what the protective mechanisms are. Operations were performed under ether anesthesia. Asprin, 200 mg per kg, was instilled into the stomach 1/2 hr postsurgery (bile duct ligation or pylorus ligation). Four hours later the rats were killed, the stomachs were examined, and mucosal lesions were scored. Bile duct ligation, but not pylorus ligation, significantly protected against aspirin-induced gastric-lesions. Bile duct ligation, in pylorus-ligated rats, inhibited gastric acid output by 78%. Instilling HCl + aspirin in bile duct-ligated rats restored lesion formation. Shunting bile to the colon (to prevent bile reflux) did not prevent aspirin lesions. Salicylate determination, to ascertain whether bile duct ligation altered asprin absorption, revealed no significant differences between bile duct ligation and aspirin, shunt + aspirin, and sham shunt + aspirin in plasma and gastric tissue salicylate concentrations. (1) Bile duct legation protects against aspirin-induced gastric mucosal lesions by inhibiting gastric HCl secretion. As a corollary, a certain amount of acid in the stomach is necessary for aspirin-induced gastric lesions to form. (2) Bile reflux is not necessary for aspirn-induced gastric lesions in the rat.", "contents": "Mechanism of prevention of aspirin-induced gastric lesions by bile duct legation in the rat. Gastric reflux of bile has been reported to be essential for the production of acute gastric mucosal lesions by intragastric aspirin in the rat. The purpose of the present study was to determine whether bile duct legation of pylorus ligation in the rat inhibits asprin-induced gastric lesions, and, if so, what the protective mechanisms are. Operations were performed under ether anesthesia. Asprin, 200 mg per kg, was instilled into the stomach 1/2 hr postsurgery (bile duct ligation or pylorus ligation). Four hours later the rats were killed, the stomachs were examined, and mucosal lesions were scored. Bile duct ligation, but not pylorus ligation, significantly protected against aspirin-induced gastric-lesions. Bile duct ligation, in pylorus-ligated rats, inhibited gastric acid output by 78%. Instilling HCl + aspirin in bile duct-ligated rats restored lesion formation. Shunting bile to the colon (to prevent bile reflux) did not prevent aspirin lesions. Salicylate determination, to ascertain whether bile duct ligation altered asprin absorption, revealed no significant differences between bile duct ligation and aspirin, shunt + aspirin, and sham shunt + aspirin in plasma and gastric tissue salicylate concentrations. (1) Bile duct legation protects against aspirin-induced gastric mucosal lesions by inhibiting gastric HCl secretion. As a corollary, a certain amount of acid in the stomach is necessary for aspirin-induced gastric lesions to form. (2) Bile reflux is not necessary for aspirn-induced gastric lesions in the rat."}
{"id": "PMID:9330", "title": "Gastric mucosal lesions produced by intravenous infusion of aspirin in cats.", "content": "Aspirin was given by continuous intravenous infusion to 35 intact cats for 7 days in doses ranging from 25 to 200 mg kg-1 day-1. Gastric mucosal lesions occurred in 50 to 70% of the animals in the various dosage groups, including deep ulcers in 20%. All of the ulcers were in antral mucosa near its border with oxyntic mucosa. The incidence of lesions, including ulcers, showed no apparent relation to the dose of aspirin. With all but the highest dose, plasma salicylate levels were within or below what is regarded as the therapeutic range for man. Asprin, 100 mg kg-1 day-1, was given for 7 days to 4 cats with pouches containing all of the antral mucosa plus some oxyntic mucosa. One or more deep ulcers occurred in the antral mucosa of the pouches in each of these 4 cats. The electrical potential difference across the mucosa did not decrease, and net fluxes of hydrogen ions out of the pouch and of sodium ions into the pouch did not increase during the 7 days of aspirin administration despite the occurrence of ulcers in the pouches. It is concluded that intravenous aspirin, in doses giving plasma levels within or below the therapeutic range for man, causes gastric mucosal lesions including deep ulcers within 7 days in cats. These lesions occur without the changes in electrical potential difference and hydrogen and sodium fluxes that are regarded as characteristic of the \"broken barrier.\"", "contents": "Gastric mucosal lesions produced by intravenous infusion of aspirin in cats. Aspirin was given by continuous intravenous infusion to 35 intact cats for 7 days in doses ranging from 25 to 200 mg kg-1 day-1. Gastric mucosal lesions occurred in 50 to 70% of the animals in the various dosage groups, including deep ulcers in 20%. All of the ulcers were in antral mucosa near its border with oxyntic mucosa. The incidence of lesions, including ulcers, showed no apparent relation to the dose of aspirin. With all but the highest dose, plasma salicylate levels were within or below what is regarded as the therapeutic range for man. Asprin, 100 mg kg-1 day-1, was given for 7 days to 4 cats with pouches containing all of the antral mucosa plus some oxyntic mucosa. One or more deep ulcers occurred in the antral mucosa of the pouches in each of these 4 cats. The electrical potential difference across the mucosa did not decrease, and net fluxes of hydrogen ions out of the pouch and of sodium ions into the pouch did not increase during the 7 days of aspirin administration despite the occurrence of ulcers in the pouches. It is concluded that intravenous aspirin, in doses giving plasma levels within or below the therapeutic range for man, causes gastric mucosal lesions including deep ulcers within 7 days in cats. These lesions occur without the changes in electrical potential difference and hydrogen and sodium fluxes that are regarded as characteristic of the \"broken barrier.\""}
{"id": "PMID:9331", "title": "Influence of acid secretory state on the gastric mucosal tolerance to back diffusion of H+.", "content": "The effect of back diffusion of H+ PON THE POTENTIAL DIFFERence (PD), electrical resistance (R), and short circuit current (Isc) of spontaneously secreting and burimamide-inhibited amphibian gastric mucosae were studied in vitro. When back diffusion of H+ was induced by the passage of an electrical current of 510 mua per cm2 from the secretory (S) side of pH 2.25 to the nutrient side (N) for 30 min, the spontaneously secreting mucosae showed small decreases in PD (23.6 leads to 16.2 mv) and Isc (80 leads to 61 mua per cm2) but no significant change in R. In the burimamide-inhibited mucosae there were marked and significantly greater decreases of PD (26.8 leads to 3.4 mv), R (473 leads to 170 ohms cm2) and Isc (50 leads to 13 mua per cm2). When back diffusion of H+ was induced by establishing a concentration gradient of H+ from S leads to N or by exposing the secretory surface to sodium taurocholate with secretory pH 2.25, the burimamide-inhibited tissue demonstrated significantly greater depression of the electrical parameters than the secreting mucosae. Intracellular pH, measured by the 5,5-dimethoxyazolidine-2,4-dione method, was significantly higher in the histamine-stimulated tissues (7.28) than in the metiamide-inhibited tissues (7.11). These studies strongly suggest that the secretory status of the mucosa and hence its acid-base status are important determinants in the tolerance of the tissue to exogenous back diffusion of H+. The measure of absolute loss of H+ From the mucosal solution alone may not be an adequate assessment of the gastric mucosal barrier.", "contents": "Influence of acid secretory state on the gastric mucosal tolerance to back diffusion of H+. The effect of back diffusion of H+ PON THE POTENTIAL DIFFERence (PD), electrical resistance (R), and short circuit current (Isc) of spontaneously secreting and burimamide-inhibited amphibian gastric mucosae were studied in vitro. When back diffusion of H+ was induced by the passage of an electrical current of 510 mua per cm2 from the secretory (S) side of pH 2.25 to the nutrient side (N) for 30 min, the spontaneously secreting mucosae showed small decreases in PD (23.6 leads to 16.2 mv) and Isc (80 leads to 61 mua per cm2) but no significant change in R. In the burimamide-inhibited mucosae there were marked and significantly greater decreases of PD (26.8 leads to 3.4 mv), R (473 leads to 170 ohms cm2) and Isc (50 leads to 13 mua per cm2). When back diffusion of H+ was induced by establishing a concentration gradient of H+ from S leads to N or by exposing the secretory surface to sodium taurocholate with secretory pH 2.25, the burimamide-inhibited tissue demonstrated significantly greater depression of the electrical parameters than the secreting mucosae. Intracellular pH, measured by the 5,5-dimethoxyazolidine-2,4-dione method, was significantly higher in the histamine-stimulated tissues (7.28) than in the metiamide-inhibited tissues (7.11). These studies strongly suggest that the secretory status of the mucosa and hence its acid-base status are important determinants in the tolerance of the tissue to exogenous back diffusion of H+. The measure of absolute loss of H+ From the mucosal solution alone may not be an adequate assessment of the gastric mucosal barrier."}
{"id": "PMID:9332", "title": "gamma-glutamyl transpeptidase of rat intestine: localization and possible role in amino acid transport.", "content": "gamma-Glutamyl transpeptidase (gamma-GT), an enzyme possibly involved in amino acid transport, was investigated in rat small intestine using the synthetic substrate L-gamma-glutamyl-p-nitroanilide. Enzyme localization and characteristics were correlated with features of amino acid uptake. gamma-GT activity copurified with sucrase and alkaline phosphatase. Activity was maximal at pH 8.2 and was stimulated by monovalent cations. The relative specificity of the gamma-GT reaction with diglycine and eight essential amino acids as substrates correlated well with the rate of intestinal absorption of this dipeptide and these amino acids as observed by others. gamma-GT activity was 12-fold greater in the jejunum than in the ileum, again in agreement with relative rates of amino acid absorption along the length of rat intestine. The specific activity of gamma-GT in villus tip cells was 10 times greater than in crypt cells, and amino acid uptake was 2 to 6 times greater with villus tip than with crypt cells. Bromosulfophthalein, a noncompetitive inhibitor of gamma-GT, inhibited amino acid uptake. These studies support the concept that membrane gamma-GT may be involved in amino acid and dipeptide uptake, and indicate that further investigation of such involvement may be conveniently pursued using mammalian small bowel.", "contents": "gamma-glutamyl transpeptidase of rat intestine: localization and possible role in amino acid transport. gamma-Glutamyl transpeptidase (gamma-GT), an enzyme possibly involved in amino acid transport, was investigated in rat small intestine using the synthetic substrate L-gamma-glutamyl-p-nitroanilide. Enzyme localization and characteristics were correlated with features of amino acid uptake. gamma-GT activity copurified with sucrase and alkaline phosphatase. Activity was maximal at pH 8.2 and was stimulated by monovalent cations. The relative specificity of the gamma-GT reaction with diglycine and eight essential amino acids as substrates correlated well with the rate of intestinal absorption of this dipeptide and these amino acids as observed by others. gamma-GT activity was 12-fold greater in the jejunum than in the ileum, again in agreement with relative rates of amino acid absorption along the length of rat intestine. The specific activity of gamma-GT in villus tip cells was 10 times greater than in crypt cells, and amino acid uptake was 2 to 6 times greater with villus tip than with crypt cells. Bromosulfophthalein, a noncompetitive inhibitor of gamma-GT, inhibited amino acid uptake. These studies support the concept that membrane gamma-GT may be involved in amino acid and dipeptide uptake, and indicate that further investigation of such involvement may be conveniently pursued using mammalian small bowel."}
{"id": "PMID:9333", "title": "Association of inflammatory bowel disease and large vascular lesions.", "content": "A case of inflammatory bowel disease with associated multiple large vessel vascular lesions similar to that seen in Takayasu's arteritis is described in a 15-year-old female. It is suggested that this type of vascular lesion may represent another rare systemic manifestation of inflammatory bowel disease.", "contents": "Association of inflammatory bowel disease and large vascular lesions. A case of inflammatory bowel disease with associated multiple large vessel vascular lesions similar to that seen in Takayasu's arteritis is described in a 15-year-old female. It is suggested that this type of vascular lesion may represent another rare systemic manifestation of inflammatory bowel disease."}
{"id": "PMID:9338", "title": "Presence or absence of inhibitors of crystal growth in bile. 1. Effect of bile on the formation of calcium phosphate, a constituent of gallstones.", "content": "When calcium and phosphate ions were mixed so that their final concentration was 4 mmol/1 and the pH was kept at 7-0, an amorphous precipitate immediately formed and this changed into crystalline material with an apatite-like structure after a period of time. The formation of either or both types of precipitate could be slowed down or prevented by adding to the crystallising medium trace amounts of pyrophosphate or citrate which are known inhibitors of the formation of calcium phosphate, or large quantities of sodium chloride which increased the ionic strength of the solution and hence the solubility of calcium phosphate, Both common duct and gallbladder bile from patients with gallstones composed of cholesterol and/or calcium carbonate had a very pronounced inhibitory action on the formation of these precipitates. Only very small amounts of bile were necessary to produce these effects, which therefore were not due to an increase in ionic strength. Ultrafiltration of bile showed that material with a molecular weight greater than 10 000 was mainly responsible for this activity. Because the inhibitor was present in both common duct and gallbladder bile, the liver is the likely source of origin. The possible identity of this material is examined. The powerful inhibitory effect of bile on the crystallisation of calcium phosphate is probably a contributory factor to the rare occurrence of the calcium phosphates, apatite and whitlockite, in gallstones.", "contents": "Presence or absence of inhibitors of crystal growth in bile. 1. Effect of bile on the formation of calcium phosphate, a constituent of gallstones. When calcium and phosphate ions were mixed so that their final concentration was 4 mmol/1 and the pH was kept at 7-0, an amorphous precipitate immediately formed and this changed into crystalline material with an apatite-like structure after a period of time. The formation of either or both types of precipitate could be slowed down or prevented by adding to the crystallising medium trace amounts of pyrophosphate or citrate which are known inhibitors of the formation of calcium phosphate, or large quantities of sodium chloride which increased the ionic strength of the solution and hence the solubility of calcium phosphate, Both common duct and gallbladder bile from patients with gallstones composed of cholesterol and/or calcium carbonate had a very pronounced inhibitory action on the formation of these precipitates. Only very small amounts of bile were necessary to produce these effects, which therefore were not due to an increase in ionic strength. Ultrafiltration of bile showed that material with a molecular weight greater than 10 000 was mainly responsible for this activity. Because the inhibitor was present in both common duct and gallbladder bile, the liver is the likely source of origin. The possible identity of this material is examined. The powerful inhibitory effect of bile on the crystallisation of calcium phosphate is probably a contributory factor to the rare occurrence of the calcium phosphates, apatite and whitlockite, in gallstones."}
{"id": "PMID:9340", "title": "[Interaction of dl-mandelamidine (Olimidine) with some antihypertensive drugs expressed in the blood pressure of conscious rats].", "content": "Hypotensive effect of dl-Mandelamidine (Olmidine, MA) in combination with some established antihypertensive drugs was studied in conscious normotensive rats. The mean blood pressure and heart rate were measured by means of a pressure transducer via a polyethylene tube inserted into the abdominal aorta of rat according to the method described by Weeks. The results obtained were as follows; 1) The hypotensive effects of guanethidine and hydrochlorothiazide were enhanced in combination with MA. 2) The hypotensive effect of reserpine was reduced by MA. 3) The hypotensive effects of clonidine, C6, propranolol and hydralazine were uneffected by MA. On the other hand, changes in heart rate induced by reserpine and C6 were increased by MA, however, those induced by guanethidine, clonidine propranolol and hydralazine were decreased by MA. The slight decrease in heart rate induced by hydrochlorothiazide was uneffected by MA. In view of our data, it is considered important that investigation of the interaction of antihypertensive drugs be done using conscious animals, as these drugs will be clinically prescribed.", "contents": "[Interaction of dl-mandelamidine (Olimidine) with some antihypertensive drugs expressed in the blood pressure of conscious rats]. Hypotensive effect of dl-Mandelamidine (Olmidine, MA) in combination with some established antihypertensive drugs was studied in conscious normotensive rats. The mean blood pressure and heart rate were measured by means of a pressure transducer via a polyethylene tube inserted into the abdominal aorta of rat according to the method described by Weeks. The results obtained were as follows; 1) The hypotensive effects of guanethidine and hydrochlorothiazide were enhanced in combination with MA. 2) The hypotensive effect of reserpine was reduced by MA. 3) The hypotensive effects of clonidine, C6, propranolol and hydralazine were uneffected by MA. On the other hand, changes in heart rate induced by reserpine and C6 were increased by MA, however, those induced by guanethidine, clonidine propranolol and hydralazine were decreased by MA. The slight decrease in heart rate induced by hydrochlorothiazide was uneffected by MA. In view of our data, it is considered important that investigation of the interaction of antihypertensive drugs be done using conscious animals, as these drugs will be clinically prescribed."}
{"id": "PMID:9341", "title": "[Metabolic fate of carteolol hydrochloride (OPC-1085), a new beta-adrenergic agent. (3) Autoradiographic total body distribution studies in mice].", "content": "Distribution of a new beta-adrenergic blocking agent, 3H-carteolol in mice was studied by whole body autoradiography. The distribution of radioactivity was observed in all organs except the eyes and brain, with particularly high specific activities in the kidneys, liver, gall bladder and content in the intestines within a short time after either oral or intravenous administration. The radioactivity was then promptly eliminated from all tissues and organs, and excreted almost entirely in the urine and bile. Propranolol is known to be distributed at a high concentration in the brain, whereas the concentration of (3H-) carteolol detectable in the brain was slight. In the adrenal gland, the radioactivity was localized in the medulla. Radioactivity was detected also in the stomach contents after the intravenous administration. The distribution of radioactivity in the fetus through the placenta was less than that in the major organs of the mother mouse, and the elimination of the activity was more rapid in the fetus than in mother. These findings indicate that carteolol and its metabolites do to some extent pass through the blood-brain barrier and placenta.", "contents": "[Metabolic fate of carteolol hydrochloride (OPC-1085), a new beta-adrenergic agent. (3) Autoradiographic total body distribution studies in mice]. Distribution of a new beta-adrenergic blocking agent, 3H-carteolol in mice was studied by whole body autoradiography. The distribution of radioactivity was observed in all organs except the eyes and brain, with particularly high specific activities in the kidneys, liver, gall bladder and content in the intestines within a short time after either oral or intravenous administration. The radioactivity was then promptly eliminated from all tissues and organs, and excreted almost entirely in the urine and bile. Propranolol is known to be distributed at a high concentration in the brain, whereas the concentration of (3H-) carteolol detectable in the brain was slight. In the adrenal gland, the radioactivity was localized in the medulla. Radioactivity was detected also in the stomach contents after the intravenous administration. The distribution of radioactivity in the fetus through the placenta was less than that in the major organs of the mother mouse, and the elimination of the activity was more rapid in the fetus than in mother. These findings indicate that carteolol and its metabolites do to some extent pass through the blood-brain barrier and placenta."}
{"id": "PMID:9342", "title": "Biochemical basis of an animal model of depressive illness--a preliminary report--.", "content": "Biochemical analyses of brain samples of an Animal Model of Depression indicate the state of motionlessness observed in response to a conditioned stimulus was due to an excess in functional activity of serotonin. An excess functional activity of serotonin may be directly responsible for human depressive illness. This conflicting conclusion to the currently popular theories of serotonin deficiency was discussed with reference to the animal and clinical data in the literature which are consistent with the conclusion.", "contents": "Biochemical basis of an animal model of depressive illness--a preliminary report--. Biochemical analyses of brain samples of an Animal Model of Depression indicate the state of motionlessness observed in response to a conditioned stimulus was due to an excess in functional activity of serotonin. An excess functional activity of serotonin may be directly responsible for human depressive illness. This conflicting conclusion to the currently popular theories of serotonin deficiency was discussed with reference to the animal and clinical data in the literature which are consistent with the conclusion."}
{"id": "PMID:9344", "title": "[Current resistence situation in a surgical and urological department].", "content": "Spectrum and sensitivity of bacteria were studied at the Surgical (534 positive wound smears) and the Urological Clinics (7879 urine specimens). Krankenhaus Nordwest, Frankfurt/M., during the period of 1969-1971 and in 1973. The most common organisms identified in wound smears were E. coli, followed by Staph. areus, Aerobacter and Proteus species. E. coli were also predominant in urine, but followed by Enterococci, Proteus and Pseudomonas. E. coli, Proteus species and especially Pseudomonas increased in number whereas Enterococci decreased. There was no pronounced increase in resistance to 9 current antibiotics as well as to chemotherapeutics during the observation period which was particularly striking in the case of Ampicillin used on a large scale. The results of our study support the presently employed therapeutic method using bactericidal antibiotics of the penicillin group in strict indications.", "contents": "[Current resistence situation in a surgical and urological department]. Spectrum and sensitivity of bacteria were studied at the Surgical (534 positive wound smears) and the Urological Clinics (7879 urine specimens). Krankenhaus Nordwest, Frankfurt/M., during the period of 1969-1971 and in 1973. The most common organisms identified in wound smears were E. coli, followed by Staph. areus, Aerobacter and Proteus species. E. coli were also predominant in urine, but followed by Enterococci, Proteus and Pseudomonas. E. coli, Proteus species and especially Pseudomonas increased in number whereas Enterococci decreased. There was no pronounced increase in resistance to 9 current antibiotics as well as to chemotherapeutics during the observation period which was particularly striking in the case of Ampicillin used on a large scale. The results of our study support the presently employed therapeutic method using bactericidal antibiotics of the penicillin group in strict indications."}
{"id": "PMID:9345", "title": "[Newer aspects in the therapy of angina pectoris].", "content": "Progress in coronary surgery has led to new aspects in the treatment of angina pectoris. According to the coronar-angiographic findings, which make an exact identification of the coronary heart disease possible, and according to the ventricular function a therapeutic strategy can be determined today with adequate safety for each individual case. The most important criterium for a decision for surgical or conservative treatment is not only the improvement of the subjective symptoms, in special forms of coronary heart disease the bypass-operation not only results in improved quality of life but also in a considerably increased survival time.", "contents": "[Newer aspects in the therapy of angina pectoris]. Progress in coronary surgery has led to new aspects in the treatment of angina pectoris. According to the coronar-angiographic findings, which make an exact identification of the coronary heart disease possible, and according to the ventricular function a therapeutic strategy can be determined today with adequate safety for each individual case. The most important criterium for a decision for surgical or conservative treatment is not only the improvement of the subjective symptoms, in special forms of coronary heart disease the bypass-operation not only results in improved quality of life but also in a considerably increased survival time."}
{"id": "PMID:9346", "title": "[Inflammatory intestinal diseases: ulcerative colitis and Crohn's disease. Early diagnosis and treatment].", "content": "Early rather characteristic symptoms are found in ulcerative colitis as well as in Crohn's disease. In these patients, but also in an advanced stage, differential diagnosis between these two disorders is possible by means of endoscopic techniques and guided biopsy. In a high percentage of patients with ulcerative colitis good results are obtained with conservative therapy, using salazopyridine alone or in combination with cortisone. Combination therapy with salazopyridine and cortisone seems to offer the best results in Crohn's disease too, however, in a certain percentage of cases surgical intervention is unavoidable.", "contents": "[Inflammatory intestinal diseases: ulcerative colitis and Crohn's disease. Early diagnosis and treatment]. Early rather characteristic symptoms are found in ulcerative colitis as well as in Crohn's disease. In these patients, but also in an advanced stage, differential diagnosis between these two disorders is possible by means of endoscopic techniques and guided biopsy. In a high percentage of patients with ulcerative colitis good results are obtained with conservative therapy, using salazopyridine alone or in combination with cortisone. Combination therapy with salazopyridine and cortisone seems to offer the best results in Crohn's disease too, however, in a certain percentage of cases surgical intervention is unavoidable."}
{"id": "PMID:9347", "title": "[Polygraphic recording of sleep under the influence of Plantival plus].", "content": "10 patients with moderate non-psychotic sleep disturbances were investigated polygraphically for a total of 14 nights each. These 14 nights were subdivided into 4 test series: Placebo was given during the first, Plantival plus during the second and third and placebo again during the fourth series. The results showed that wakefulness decreased after the application of Plantival plus and that there was an increase in deep sleep. These effects could be observed mainly during the first hour of sleep and disappeared gradually during the later sleeping hours. REM-phases were not influenced by the medication. Due to these observations, Plantival plus should mainly be applicated when disturbances in falling asleep and problems in sleeping continuously occur. In case interrupted sleep in the early morning hours has been found, this preparation could be applicated only in combination with other kinds of treatment.", "contents": "[Polygraphic recording of sleep under the influence of Plantival plus]. 10 patients with moderate non-psychotic sleep disturbances were investigated polygraphically for a total of 14 nights each. These 14 nights were subdivided into 4 test series: Placebo was given during the first, Plantival plus during the second and third and placebo again during the fourth series. The results showed that wakefulness decreased after the application of Plantival plus and that there was an increase in deep sleep. These effects could be observed mainly during the first hour of sleep and disappeared gradually during the later sleeping hours. REM-phases were not influenced by the medication. Due to these observations, Plantival plus should mainly be applicated when disturbances in falling asleep and problems in sleeping continuously occur. In case interrupted sleep in the early morning hours has been found, this preparation could be applicated only in combination with other kinds of treatment."}
{"id": "PMID:9348", "title": "Poly(adenosine diphosphate ribose) is covalently linked to nuclear proteins by two types of bonds.", "content": "(ADP-ribose)n residues formed by short-term incubation of adult rat liver and Ehrlich carcinoma nuclei with labeled NAD were analyzed by Cs2SO4/guanidinium chloride/urea density gradient centrifugation. Comparison with samples in which the protein had been completely digested revealed that most, or probably all, acid-insoluble (ADP-ribose)n chains are covalently bound to nuclear proteins, as is true for the short, acid-soluble (ADP-ribose)n chains. Complete release of (ADP-ribose)n chains is effected by dilute alkali. In contrast, NH2OH liberated only part of the long and the short (ADP-ribose)n residues from the protein conjugates, indicating two types of bonds, both alkali-labile, but only one susceptible to neutral hydroxylamine. Both types of bonds were equally distributed among acid-soluble and acid-insoluble (ADP-ribose)n chains. -Stability of the (ADP-ribose)n protein conjugates during isolation is only guaranteed at pH values below 7.", "contents": "Poly(adenosine diphosphate ribose) is covalently linked to nuclear proteins by two types of bonds. (ADP-ribose)n residues formed by short-term incubation of adult rat liver and Ehrlich carcinoma nuclei with labeled NAD were analyzed by Cs2SO4/guanidinium chloride/urea density gradient centrifugation. Comparison with samples in which the protein had been completely digested revealed that most, or probably all, acid-insoluble (ADP-ribose)n chains are covalently bound to nuclear proteins, as is true for the short, acid-soluble (ADP-ribose)n chains. Complete release of (ADP-ribose)n chains is effected by dilute alkali. In contrast, NH2OH liberated only part of the long and the short (ADP-ribose)n residues from the protein conjugates, indicating two types of bonds, both alkali-labile, but only one susceptible to neutral hydroxylamine. Both types of bonds were equally distributed among acid-soluble and acid-insoluble (ADP-ribose)n chains. -Stability of the (ADP-ribose)n protein conjugates during isolation is only guaranteed at pH values below 7."}
{"id": "PMID:9349", "title": "On the mechanism and some properties of vinylacetyl-CoA delta-isomerase of Clostridium kluyveri.", "content": "Vinylacetyl-CoA delta-isomerase from Clostridium kluyveri grown on ethanol/acetate was purified 32-fold. The enzyme is rather labile. All experiments were conducted with the substrate analog thioester of vinylacetic acid and N-acetylchysteamine (vinylacetyl-SEtNAc (1 f)). 3-Butinoyl-SEtNAc is a strong inhibitor of the isomerase. The hydrogen transfer from the alpha-position of vinylacetyl-SEtNAc to the gamma-position of 2-butenoyl-SEtNAc (1f leads to 2 f) occurs partially intramolecularly (40-50%) as shown by experiments in 3HOH/H2O, 2H2O and 3HOH/2H2O as well as by experiments with [2,3-3H]vinylacetyl-SEtNAc. Only 0.07 atoms of tritium are incorporated into the gamma-position of 2f when the isomerisation takes place in 3HOH/H2O. The extent of intramolecularity is in agreement with results of experiments conducted in 2H2O with whole cells [4]. The reaction 1f leads to 2f shows no or only negligiebl reversibility and at least no considerable isotope effect.", "contents": "On the mechanism and some properties of vinylacetyl-CoA delta-isomerase of Clostridium kluyveri. Vinylacetyl-CoA delta-isomerase from Clostridium kluyveri grown on ethanol/acetate was purified 32-fold. The enzyme is rather labile. All experiments were conducted with the substrate analog thioester of vinylacetic acid and N-acetylchysteamine (vinylacetyl-SEtNAc (1 f)). 3-Butinoyl-SEtNAc is a strong inhibitor of the isomerase. The hydrogen transfer from the alpha-position of vinylacetyl-SEtNAc to the gamma-position of 2-butenoyl-SEtNAc (1f leads to 2 f) occurs partially intramolecularly (40-50%) as shown by experiments in 3HOH/H2O, 2H2O and 3HOH/2H2O as well as by experiments with [2,3-3H]vinylacetyl-SEtNAc. Only 0.07 atoms of tritium are incorporated into the gamma-position of 2f when the isomerisation takes place in 3HOH/H2O. The extent of intramolecularity is in agreement with results of experiments conducted in 2H2O with whole cells [4]. The reaction 1f leads to 2f shows no or only negligiebl reversibility and at least no considerable isotope effect."}
{"id": "PMID:9350", "title": "A kallikrein-specific inhibitor in rat kidney tubules.", "content": "A kallikrein inhibitor was found in tubules of the rat kidney and purified by chromatography on Sephadex G-100. The molecular weight of the inhibitor, estimated by gel filtration and dodecylsulfate electrophoresis, is about 4700. It inhibits the following kallikreins: porcine submanidbular and pancreatic kallikrein, rat kidney and urine kallikrein, and human urine and plasma kallikrein. An inhibition of bovine trypsin was not observed.", "contents": "A kallikrein-specific inhibitor in rat kidney tubules. A kallikrein inhibitor was found in tubules of the rat kidney and purified by chromatography on Sephadex G-100. The molecular weight of the inhibitor, estimated by gel filtration and dodecylsulfate electrophoresis, is about 4700. It inhibits the following kallikreins: porcine submanidbular and pancreatic kallikrein, rat kidney and urine kallikrein, and human urine and plasma kallikrein. An inhibition of bovine trypsin was not observed."}
{"id": "PMID:9351", "title": "[Preparation and some properties of immobilized trypsin from the crayfish Cambarus affinis Say (author's transl)].", "content": "The anionic tryptic enzyme from the crayfish (crayfish trypsin) was adsorbed to DEAE-Sephadex A-50 and covalently coupled to BrCN-activated Sepharose 4B and porous glass loaded with isothiocyanate propyl groups (ITC-glass). The relative activities against p-tosylarginine methyl ester (TosArgOMe) were found to be 30 to 100% for DEAE-Sephadex crayfish trypsin, 20 to 53% for Sepharose crayfish trypsin, and 17 to 38% for ITC-glass crayfish trypsin. The relative activities rise with declining protein content of the enzyme matrix complexes. The highest relative proteinase activities (substrate: 1% casein) were obtained with Sepharose crayfish trypsin (74%), followed by DEAE-Sephadex crayfish trypsin (68%) and ITC-glass crayfish trypsin (45%). Similar results are obtained with protamine and native lactate dehydrogenase as substrates. In accordance with the Sepharose bovine trypsin complex the apparent Michaelis constant (Km(app)) of the Sepharose crayfish trypsin with TosArgOMe was found to be markedly higher than that of the native enzyme. The pH-activity profiles of the crayfish trypsin derivatives using TosArgOMe as substrate were shown to be displaced towards more alkaline pH values by 0.5 (ITC-glass crayfish trypsin) and 1 (Sepharose crayfish trypsin) pH units, respectively, or towards more acidic pH values (by 1.5 pH units) with the polycationic derivative (DEAE-Sephadex crayfish trypsin) as compared to the native enzyme (optimum pH 8.6). Concerning the temperature stability of the derivatives, Sepharose crayfish trypsin was more stabile, ITC-glass crayfish trypsin behaves like the native crayfish  trypsin, and DEAE-Sephadex crayfish trypsin was more sensitive at elevated temperatures as compared to the soluble enzyme. The properties of the crayfish trypsin derivatives are compared with the properties of the bovine analogues.", "contents": "[Preparation and some properties of immobilized trypsin from the crayfish Cambarus affinis Say (author's transl)]. The anionic tryptic enzyme from the crayfish (crayfish trypsin) was adsorbed to DEAE-Sephadex A-50 and covalently coupled to BrCN-activated Sepharose 4B and porous glass loaded with isothiocyanate propyl groups (ITC-glass). The relative activities against p-tosylarginine methyl ester (TosArgOMe) were found to be 30 to 100% for DEAE-Sephadex crayfish trypsin, 20 to 53% for Sepharose crayfish trypsin, and 17 to 38% for ITC-glass crayfish trypsin. The relative activities rise with declining protein content of the enzyme matrix complexes. The highest relative proteinase activities (substrate: 1% casein) were obtained with Sepharose crayfish trypsin (74%), followed by DEAE-Sephadex crayfish trypsin (68%) and ITC-glass crayfish trypsin (45%). Similar results are obtained with protamine and native lactate dehydrogenase as substrates. In accordance with the Sepharose bovine trypsin complex the apparent Michaelis constant (Km(app)) of the Sepharose crayfish trypsin with TosArgOMe was found to be markedly higher than that of the native enzyme. The pH-activity profiles of the crayfish trypsin derivatives using TosArgOMe as substrate were shown to be displaced towards more alkaline pH values by 0.5 (ITC-glass crayfish trypsin) and 1 (Sepharose crayfish trypsin) pH units, respectively, or towards more acidic pH values (by 1.5 pH units) with the polycationic derivative (DEAE-Sephadex crayfish trypsin) as compared to the native enzyme (optimum pH 8.6). Concerning the temperature stability of the derivatives, Sepharose crayfish trypsin was more stabile, ITC-glass crayfish trypsin behaves like the native crayfish  trypsin, and DEAE-Sephadex crayfish trypsin was more sensitive at elevated temperatures as compared to the soluble enzyme. The properties of the crayfish trypsin derivatives are compared with the properties of the bovine analogues."}
{"id": "PMID:9352", "title": "Identity of kynurenine: pyruvate aminotransferase with histidine: pyruvate aminotransferase.", "content": "Kynurenine pyruvate aminotransferase was purified from rat kidney. The purified enzyme had an isoelectric point of pH 5.2 and a pH optimum of 9.3. The enzyme was active with pyruvate as amino acceptor but not with 2-oxoglutarate, and utilized various aromatic amino acids as amino donors. L-Amino acids were effective in the following order of activity: histidine greather than phenylalanine greater than kynurenine greater than tyrosine greater than tryptophan greater than 5-hydroxytryptophan. The apparent Km values were about 0.63 mM, 1.4 mM and 0.09 mM for histidine, kynurenine and phenylalanine, respectively. Km values for pyruvate were 5.5 mM with histidine as amino donor, 1.3 mM with kynurenine and 8.5 mM with phenylalanine. Kynurenine pyruvate aminotransferase activity of the enzyme was inhibited by the addition of histidine or phenylalanine. The molecular weights determined by gel filtration and sucrose density gradient centrifugation were approximately 76000 and 79000, respectively. On the basis of purification ratio, substrate specificity, inhibition by common substrates, subcellular distribution, isoelectric focusing and polyacrylamide-gel electrophoresis, it is suggested that kynurenine pyruvate aminotransferase is identical with histidine pyruvate aminotransferase and also with phenylalanine pyruvate aminotransferase. The physiological significance of the enzyme is discussed.", "contents": "Identity of kynurenine: pyruvate aminotransferase with histidine: pyruvate aminotransferase. Kynurenine pyruvate aminotransferase was purified from rat kidney. The purified enzyme had an isoelectric point of pH 5.2 and a pH optimum of 9.3. The enzyme was active with pyruvate as amino acceptor but not with 2-oxoglutarate, and utilized various aromatic amino acids as amino donors. L-Amino acids were effective in the following order of activity: histidine greather than phenylalanine greater than kynurenine greater than tyrosine greater than tryptophan greater than 5-hydroxytryptophan. The apparent Km values were about 0.63 mM, 1.4 mM and 0.09 mM for histidine, kynurenine and phenylalanine, respectively. Km values for pyruvate were 5.5 mM with histidine as amino donor, 1.3 mM with kynurenine and 8.5 mM with phenylalanine. Kynurenine pyruvate aminotransferase activity of the enzyme was inhibited by the addition of histidine or phenylalanine. The molecular weights determined by gel filtration and sucrose density gradient centrifugation were approximately 76000 and 79000, respectively. On the basis of purification ratio, substrate specificity, inhibition by common substrates, subcellular distribution, isoelectric focusing and polyacrylamide-gel electrophoresis, it is suggested that kynurenine pyruvate aminotransferase is identical with histidine pyruvate aminotransferase and also with phenylalanine pyruvate aminotransferase. The physiological significance of the enzyme is discussed."}
{"id": "PMID:9353", "title": "Studies on the proteinase-A inhibitor I3A from yeast.", "content": "The purification and some properties of the two inhibitors I2A and I3A of proteinase A from yeast have previously been described [Saheki et al, (1974) Eur. J. Biochem. 47, 325]. An improved method for the preparation of I3A which is less time-consuming and leads to higher yields is presented. Based on amino acid analysis, I3A contains 68 amino acids per molecule. The molecular weight was 7676. The inhibitor contained no proline, no arginine, no cysteine and no tryptophan, but did contain a large number of the polar amino acids glutamate + glutamine, aspartate + asparagine and lysine. Neither by dansylation nor by Edman degradation could an N-terminal amino acid be detected. Changes in the circular dichroism upon transition from pH 6.9 to 3.0 suggest different tertiary structures at these pH values. Experiments on the kinetics of inhibition of proteinase A revealed an apparent Ki value of 5.5 X 10(-8) M for I3A and 1.6 X 10(-8) M for pepstatin. A \"non-stoichiometric inhibition\" of a \"pseudo-irreversible\" type is concluded from the kinetic data. A hydrophobic type of binding of I3A to yeast proteinase A is suggested from experiments demonstrating a large decrease in the percentage of inhibition caused by addition of 2 M urea, 2 M guanidine hydrochloride, 0.125% Triton or 0.125% cholic acid.", "contents": "Studies on the proteinase-A inhibitor I3A from yeast. The purification and some properties of the two inhibitors I2A and I3A of proteinase A from yeast have previously been described [Saheki et al, (1974) Eur. J. Biochem. 47, 325]. An improved method for the preparation of I3A which is less time-consuming and leads to higher yields is presented. Based on amino acid analysis, I3A contains 68 amino acids per molecule. The molecular weight was 7676. The inhibitor contained no proline, no arginine, no cysteine and no tryptophan, but did contain a large number of the polar amino acids glutamate + glutamine, aspartate + asparagine and lysine. Neither by dansylation nor by Edman degradation could an N-terminal amino acid be detected. Changes in the circular dichroism upon transition from pH 6.9 to 3.0 suggest different tertiary structures at these pH values. Experiments on the kinetics of inhibition of proteinase A revealed an apparent Ki value of 5.5 X 10(-8) M for I3A and 1.6 X 10(-8) M for pepstatin. A \"non-stoichiometric inhibition\" of a \"pseudo-irreversible\" type is concluded from the kinetic data. A hydrophobic type of binding of I3A to yeast proteinase A is suggested from experiments demonstrating a large decrease in the percentage of inhibition caused by addition of 2 M urea, 2 M guanidine hydrochloride, 0.125% Triton or 0.125% cholic acid."}
{"id": "PMID:9359", "title": "Antigenicity of type-specific pneumococcal polysaccharides in rats.", "content": "Hemagglutinating antibody responses of Lewis-Wistar and Sprague-Dawley rats to graded doses of type-specific pneumococcal polysaccharide were measured. Rats given a small dose (0.2 to 50 mug)of type 1 or 8 polysaccharide intraperitoneally developed type-specific hemagglutinating antibody. Rats given larger doses of polysaccharide (greater than or equal to200 mug) did not develop detectable hemagglutinating antibody, and they were unresponsive to a subsequence injection of a small (and normally antigenic) dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide, and the kinetics of antigen clearance in these animals resembled that reported for mice with polysaccharide immunological paralysis. These results indicate that a phenomenon resembling immunological paralysis with type-specific pneumococcal polysaccharides can be produced in rats.", "contents": "Antigenicity of type-specific pneumococcal polysaccharides in rats. Hemagglutinating antibody responses of Lewis-Wistar and Sprague-Dawley rats to graded doses of type-specific pneumococcal polysaccharide were measured. Rats given a small dose (0.2 to 50 mug)of type 1 or 8 polysaccharide intraperitoneally developed type-specific hemagglutinating antibody. Rats given larger doses of polysaccharide (greater than or equal to200 mug) did not develop detectable hemagglutinating antibody, and they were unresponsive to a subsequence injection of a small (and normally antigenic) dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide. There was prolonged antigenemia in rats injected with a large dose of polysaccharide, and the kinetics of antigen clearance in these animals resembled that reported for mice with polysaccharide immunological paralysis. These results indicate that a phenomenon resembling immunological paralysis with type-specific pneumococcal polysaccharides can be produced in rats."}
{"id": "PMID:9360", "title": "In vitro differentiation and pH sensitivity of field and cell culture-attentuated strains of transmissible gastroenteritis virus.", "content": "Characteristics of four transmissible gastroenteritis (TGE) virus field strains (Miller, Purdue, Bl, and V203) and four cell culture-attenuated strains (Purdue, SH, CKp, and Bl) were studied to find methods of differentiation between the two groups of viruses. TGE field virus strains did not replicate as well as attenuated strains at 37 C and could not be passaged serially for more than four to six passages at 33 C. There were clear differences in plaque size when the strains were compared. Field strains had average plaque sizes ranging from 3.59 to 3.15 mm, whereas attenuated strains induced plaques that were larger than 4.2 mm. Variations were observed in stability of strains at pH 3.0. Field strains and cell culture-attenuated strains CKp-270 and SH-114 were reduced in titer by about 1 log10. A reduction of about 3 log10, however, was obtained with cell culture strains B1-300 and Purdue-113.", "contents": "In vitro differentiation and pH sensitivity of field and cell culture-attentuated strains of transmissible gastroenteritis virus. Characteristics of four transmissible gastroenteritis (TGE) virus field strains (Miller, Purdue, Bl, and V203) and four cell culture-attenuated strains (Purdue, SH, CKp, and Bl) were studied to find methods of differentiation between the two groups of viruses. TGE field virus strains did not replicate as well as attenuated strains at 37 C and could not be passaged serially for more than four to six passages at 33 C. There were clear differences in plaque size when the strains were compared. Field strains had average plaque sizes ranging from 3.59 to 3.15 mm, whereas attenuated strains induced plaques that were larger than 4.2 mm. Variations were observed in stability of strains at pH 3.0. Field strains and cell culture-attenuated strains CKp-270 and SH-114 were reduced in titer by about 1 log10. A reduction of about 3 log10, however, was obtained with cell culture strains B1-300 and Purdue-113."}
{"id": "PMID:9361", "title": "Hemagglutination by equine infectious anemia virus.", "content": "Equine infectious anemia (EIA) virus which was propagated on an equine dermal cell line agglutinated guinea pig erythrocytes. Viral fluids containing about 10(7.5) mean tissue culture infective doses/ml showed hemagglutinating (HA) titers ranging from 16 to 32 units/0.05 ml. Results of cesium chloride equilibrium density gradient centrifugation revealed that the hemagglutinin was inseparable from the virus particles. The hemagglutination reaction persisted over a wide range of temperature and pH, and the absence of divalent cations did not decrease its activity. The HA activity was stable at 4 degrees C but not at 56 degreesC. The activity was destroyed by virus-disrupting lipid solvents and moderately sensitive to a proteolytic enzyme. Neuraminidase enhanced HA activity slightly. Phospholipase C had no effect on HA titer, although it completely inactivated infectivity. It was relatively stable to ultraviolet irradiation. Thus, the hemagglutinin appears to be closely associated with virus particles, and its activity is dependent on the presence of its lipids and proteins. Hemagglutination was inhibited by sera from horses infected with EIA virus. Hemagglutinin receptors on the erythrocytes were inactivated by a proteolytic enzyme and formaldehyde but were not influenced by neuraminidase, sodium deoxycholate, or KIO4.", "contents": "Hemagglutination by equine infectious anemia virus. Equine infectious anemia (EIA) virus which was propagated on an equine dermal cell line agglutinated guinea pig erythrocytes. Viral fluids containing about 10(7.5) mean tissue culture infective doses/ml showed hemagglutinating (HA) titers ranging from 16 to 32 units/0.05 ml. Results of cesium chloride equilibrium density gradient centrifugation revealed that the hemagglutinin was inseparable from the virus particles. The hemagglutination reaction persisted over a wide range of temperature and pH, and the absence of divalent cations did not decrease its activity. The HA activity was stable at 4 degrees C but not at 56 degreesC. The activity was destroyed by virus-disrupting lipid solvents and moderately sensitive to a proteolytic enzyme. Neuraminidase enhanced HA activity slightly. Phospholipase C had no effect on HA titer, although it completely inactivated infectivity. It was relatively stable to ultraviolet irradiation. Thus, the hemagglutinin appears to be closely associated with virus particles, and its activity is dependent on the presence of its lipids and proteins. Hemagglutination was inhibited by sera from horses infected with EIA virus. Hemagglutinin receptors on the erythrocytes were inactivated by a proteolytic enzyme and formaldehyde but were not influenced by neuraminidase, sodium deoxycholate, or KIO4."}
{"id": "PMID:9362", "title": "Humoral immunity to Streptococcus pneumoniae induced by a pneumococcal ribosomal protein fraction.", "content": "Isolation of a protective subfraction of ribosomes from Streptococcus pneumoniae has been achieved, and the immune response it induces has been investigated. Mice immunized with pneumococcal ribosomes or purified protein extracted from the ribosomal preparation (2-CE protein) exhibit similar survival rates upon challenge by virulent S. pneumoniae. In contrast, recipients of purified ribosomal ribonucleic acid were never protected against pneumococcal challenge. Serum from mice immunized with pneumococcal ribosomes or 2-CE protein passively immunized syngeneic recipients against pneumococcal challenge, whereas spleen cells from the same donors were unable to transfer immunity. Passive immunization with antiribosome serum could be abrogated by absorption with whole ribosomes, 2-CE protein, or various serotypes of S. pneumoniae (capsular types 2, 3, 6, and 14). Antiribosome serum significantly enhanced clearance of S. pneumoniae from mouse blood in vivo and in vitro. This required phagocytic cells, since antiribosome serum alone, with or without complement, supported growth of S. pneumoniae to an extent comparable to normal serum. The data suggest that the primary immunogen of pneumococcal ribosomes resides in the protein fraction. Further, the immunity induced by the protein fraction is mediated by antibody that appears to function as an opsonin for S. pneumoniae.", "contents": "Humoral immunity to Streptococcus pneumoniae induced by a pneumococcal ribosomal protein fraction. Isolation of a protective subfraction of ribosomes from Streptococcus pneumoniae has been achieved, and the immune response it induces has been investigated. Mice immunized with pneumococcal ribosomes or purified protein extracted from the ribosomal preparation (2-CE protein) exhibit similar survival rates upon challenge by virulent S. pneumoniae. In contrast, recipients of purified ribosomal ribonucleic acid were never protected against pneumococcal challenge. Serum from mice immunized with pneumococcal ribosomes or 2-CE protein passively immunized syngeneic recipients against pneumococcal challenge, whereas spleen cells from the same donors were unable to transfer immunity. Passive immunization with antiribosome serum could be abrogated by absorption with whole ribosomes, 2-CE protein, or various serotypes of S. pneumoniae (capsular types 2, 3, 6, and 14). Antiribosome serum significantly enhanced clearance of S. pneumoniae from mouse blood in vivo and in vitro. This required phagocytic cells, since antiribosome serum alone, with or without complement, supported growth of S. pneumoniae to an extent comparable to normal serum. The data suggest that the primary immunogen of pneumococcal ribosomes resides in the protein fraction. Further, the immunity induced by the protein fraction is mediated by antibody that appears to function as an opsonin for S. pneumoniae."}
{"id": "PMID:9363", "title": "Factors influencing heat-labile Escherichia coli enterotoxin activity.", "content": "In this study, conditions for production, detection, and storage of heat-labile Escherichia coli enterotoxin (LT) in culture filtrates from E. coli H-10407 were defined by using the adrenal tumor cell assay system. An enriched medium containing 0.6% yeast extract, 2% Casamino Acids, and 0.25% glucose buffered at pH 8.5 produced the highest LT activity of the various test media. In E. coli strain H-10407, LT activity was markedly decreased if the initial pH of the culture media was reduced to pH 7.5 or less. In contrast to E. coli P-263, if strain H-10407 was grown in the presence of mitomycin C there was no increase in LT production. Crude-culture filtrates containing LT can be stored at 4 degrees C for several days without an appreciable loss of activity; however, for long-term storage lyophilization or freezing at -70 degrees C is recommended.", "contents": "Factors influencing heat-labile Escherichia coli enterotoxin activity. In this study, conditions for production, detection, and storage of heat-labile Escherichia coli enterotoxin (LT) in culture filtrates from E. coli H-10407 were defined by using the adrenal tumor cell assay system. An enriched medium containing 0.6% yeast extract, 2% Casamino Acids, and 0.25% glucose buffered at pH 8.5 produced the highest LT activity of the various test media. In E. coli strain H-10407, LT activity was markedly decreased if the initial pH of the culture media was reduced to pH 7.5 or less. In contrast to E. coli P-263, if strain H-10407 was grown in the presence of mitomycin C there was no increase in LT production. Crude-culture filtrates containing LT can be stored at 4 degrees C for several days without an appreciable loss of activity; however, for long-term storage lyophilization or freezing at -70 degrees C is recommended."}
{"id": "PMID:9364", "title": "Factors influencing the immune enhancement of intrapulmonary bactericidal mechanisms.", "content": "The effect of specific immunization on the antibacterial defense mechanisms of the murine lung was assessed against Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus aureus (Smith), Serratia marcescens, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. Immunization by aerosol inhalation significantly enhanced the intrapulmonary killing of Pseudomonas aeruginosa and Proteus mirabilis but not the remaining organisms. With P. mirabilis, systemic immunization induced higher titers of specific serum agglutinins as compared with local respiratory tract immunization; however, local immunization was more effective in enhancing pulmonary bactericidal activity than was parenteral vaccination. Passive immunity against P. mirabilis or aerogenic challenge with preopsonized P. mirabilis significantly enhanced intrapulmonary killing of the homologous organism. With S. aureus, pulmonary bactericidal activity was not accelerated by aerosol challenge with the preopsonized organism, nor was it accelerated in passively immunized mice. These data demonstrate that the immune enhancement of pulmonary bactericidal activity is governed by the bacterium used for challenge and the route of immunization. The results further demonstrate that with P. mirabilis, antibody-mediated mechanisms are involved in the immune enhancement of pulmonary bactericidal activity.", "contents": "Factors influencing the immune enhancement of intrapulmonary bactericidal mechanisms. The effect of specific immunization on the antibacterial defense mechanisms of the murine lung was assessed against Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus aureus (Smith), Serratia marcescens, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. Immunization by aerosol inhalation significantly enhanced the intrapulmonary killing of Pseudomonas aeruginosa and Proteus mirabilis but not the remaining organisms. With P. mirabilis, systemic immunization induced higher titers of specific serum agglutinins as compared with local respiratory tract immunization; however, local immunization was more effective in enhancing pulmonary bactericidal activity than was parenteral vaccination. Passive immunity against P. mirabilis or aerogenic challenge with preopsonized P. mirabilis significantly enhanced intrapulmonary killing of the homologous organism. With S. aureus, pulmonary bactericidal activity was not accelerated by aerosol challenge with the preopsonized organism, nor was it accelerated in passively immunized mice. These data demonstrate that the immune enhancement of pulmonary bactericidal activity is governed by the bacterium used for challenge and the route of immunization. The results further demonstrate that with P. mirabilis, antibody-mediated mechanisms are involved in the immune enhancement of pulmonary bactericidal activity."}
{"id": "PMID:9365", "title": "Purification and properties of streptococcal hyaluronate lyase.", "content": "Hyaluronate lyase (hyaluronidase) has been purified and characterized from a group A type 4 Streptococcus. Production of the enzyme was favored by growth in trypsinized veal infusion in the presence of hyaluronate oligosaccharide and tetrasaccharide. Detectable enzymatic activity was diminished in the presence of N-acetylglucosamine and glucuronic acid. Purification of hyaluronate lyase consisted of 40 to 60% ammonium sulfate precipitation, diethylaminoethyl A-50 Sephadex ion-exchange chromatography, gel filtration with G-200 Sephadex, and adsorption to Sepharose 6B. Purified enzyme was antigenically homogeneous and free of proteinase, deoxyribonuclease, streptolysin 0, and streptokinase. Active hyaluronate lyase was recovered from neutral polyacrylamide gels, and it appeared to be a glycoprotein. A single band was detected by sodium dodecyl sulfate-acrylamide electrophoresis, which had a molecular weight of approximately 50,000. A molecular weight of 70,000 was observed by gel filtration. The purified enzyme had a Km of 3.8 x 10(-4) and a pH optimum of 6.0. Reducing agents increased the activity of crude enzyme at least threefold and were necessary to prevent inactivation of the purified enzyme.", "contents": "Purification and properties of streptococcal hyaluronate lyase. Hyaluronate lyase (hyaluronidase) has been purified and characterized from a group A type 4 Streptococcus. Production of the enzyme was favored by growth in trypsinized veal infusion in the presence of hyaluronate oligosaccharide and tetrasaccharide. Detectable enzymatic activity was diminished in the presence of N-acetylglucosamine and glucuronic acid. Purification of hyaluronate lyase consisted of 40 to 60% ammonium sulfate precipitation, diethylaminoethyl A-50 Sephadex ion-exchange chromatography, gel filtration with G-200 Sephadex, and adsorption to Sepharose 6B. Purified enzyme was antigenically homogeneous and free of proteinase, deoxyribonuclease, streptolysin 0, and streptokinase. Active hyaluronate lyase was recovered from neutral polyacrylamide gels, and it appeared to be a glycoprotein. A single band was detected by sodium dodecyl sulfate-acrylamide electrophoresis, which had a molecular weight of approximately 50,000. A molecular weight of 70,000 was observed by gel filtration. The purified enzyme had a Km of 3.8 x 10(-4) and a pH optimum of 6.0. Reducing agents increased the activity of crude enzyme at least threefold and were necessary to prevent inactivation of the purified enzyme."}
{"id": "PMID:9366", "title": "Hypnotic and minor tranquilizer use among inpatients and after discharge.", "content": "A major concern in prescribing hypnotics and minor tranquilizers in the hospital is that long-term habituation might develop. Former psychiatric inpatients were surveyed to assess hypnotic and minor tranquilizer use following discharge. Patients who used flurazepam and chloral hydrate as inpatients were no more likely to use these hypnotics as outpatients than patients who received no hypnotics as inpatients. There was a significant association between inpatient and outpatient use of minor tranquilizers. Outpatient use of minor tranquilizers was also significantly associated with outpatient hypnotic use.", "contents": "Hypnotic and minor tranquilizer use among inpatients and after discharge. A major concern in prescribing hypnotics and minor tranquilizers in the hospital is that long-term habituation might develop. Former psychiatric inpatients were surveyed to assess hypnotic and minor tranquilizer use following discharge. Patients who used flurazepam and chloral hydrate as inpatients were no more likely to use these hypnotics as outpatients than patients who received no hypnotics as inpatients. There was a significant association between inpatient and outpatient use of minor tranquilizers. Outpatient use of minor tranquilizers was also significantly associated with outpatient hypnotic use."}
{"id": "PMID:9367", "title": "Kinetics and control of bovine adrenal glucose-6-phosphate dehydrogenase.", "content": "Michaelis-Menten kinetics are observed in studies of highly purified bovine adrenal glucose-6-phosphate dehydrogenase at pH8.0 in 0.1 M bicine. The Km for NADP+ is 3.8 muM and for glucose-6-phosphate, 61 muM. At pH 6.9 Km for NADP+ increases to 6.5 muM. The enzyme is inhibited by NADPH both at pH 6.8 and at 8.0 with a Kip of 2.36 muM at pH 8.0. Inhibition is competitive with respect to both substrates implying that addition of substrates is random ordered. The data are also interpreted in terms of \"reducing charge\", the mole fraction of coenzyme in the reduced form. This appears to be the major mechanism for regulation of the pentose shunt. D-glucose, oxidized by the enzyme at a very slow rate, is also a competitive inhibitor for the natural substrate with a Ki of 0.29 M. Phosphate is a competitive inhibitor for glucose-6-phosphate oxidation but both phosphate and sulfate accelerate glucose oxidation suggesting a common binding site for the two anions and the phosphate of the natural substrate. While binding of ACTH to our enzyme preparations has been observed, we have not been able, in spite of repeated attempts, to demonstrate augmentation of the activity of the enzyme by the addition of ACTH.", "contents": "Kinetics and control of bovine adrenal glucose-6-phosphate dehydrogenase. Michaelis-Menten kinetics are observed in studies of highly purified bovine adrenal glucose-6-phosphate dehydrogenase at pH8.0 in 0.1 M bicine. The Km for NADP+ is 3.8 muM and for glucose-6-phosphate, 61 muM. At pH 6.9 Km for NADP+ increases to 6.5 muM. The enzyme is inhibited by NADPH both at pH 6.8 and at 8.0 with a Kip of 2.36 muM at pH 8.0. Inhibition is competitive with respect to both substrates implying that addition of substrates is random ordered. The data are also interpreted in terms of \"reducing charge\", the mole fraction of coenzyme in the reduced form. This appears to be the major mechanism for regulation of the pentose shunt. D-glucose, oxidized by the enzyme at a very slow rate, is also a competitive inhibitor for the natural substrate with a Ki of 0.29 M. Phosphate is a competitive inhibitor for glucose-6-phosphate oxidation but both phosphate and sulfate accelerate glucose oxidation suggesting a common binding site for the two anions and the phosphate of the natural substrate. While binding of ACTH to our enzyme preparations has been observed, we have not been able, in spite of repeated attempts, to demonstrate augmentation of the activity of the enzyme by the addition of ACTH."}
{"id": "PMID:9371", "title": "[A medical-legal question of hearing impairment following vaccination (author's transl)].", "content": "Three months following smallpox vaccination, a child was found to have profound sensory deafness. A medical-legal opinion in 1962 found no relationship between vaccination and deafness. However, when subsequent judgement appeal was made, the legality of the initial decision had to be justified. The consequence of the case, supported by available publication, indicated that a close temporal probability between vaccination and postvaccinial cerebral complication was required to justify any further legal claim. This was not considered to be a factor in the present case since the discovery of a goitre in the patient in association with an iodine dysfunction uncovered a Pendred's syndrome as the cause for the patient's hearing loss.", "contents": "[A medical-legal question of hearing impairment following vaccination (author's transl)]. Three months following smallpox vaccination, a child was found to have profound sensory deafness. A medical-legal opinion in 1962 found no relationship between vaccination and deafness. However, when subsequent judgement appeal was made, the legality of the initial decision had to be justified. The consequence of the case, supported by available publication, indicated that a close temporal probability between vaccination and postvaccinial cerebral complication was required to justify any further legal claim. This was not considered to be a factor in the present case since the discovery of a goitre in the patient in association with an iodine dysfunction uncovered a Pendred's syndrome as the cause for the patient's hearing loss."}
{"id": "PMID:9372", "title": "A pressure- and flow-insensitive reference electrode liquid junction.", "content": "The design and construction of a pressure- and flow-insensitive reference liquid junction for use in ion concentration electrode measuring systems is described. The junction is inexpensive, is very easily and rapidly constructed, is rugged, and is adaptable to various applications. When used in a pH-measuring system, drift, pressure artifacts, and flow artifacts are negligible. The response time of the system appears to be less than 10 ms. Using the pH electrode device as described, the dissociation reaction rate constant of H2CO3 at 24 degrees C was determined to be 22 s-1.", "contents": "A pressure- and flow-insensitive reference electrode liquid junction. The design and construction of a pressure- and flow-insensitive reference liquid junction for use in ion concentration electrode measuring systems is described. The junction is inexpensive, is very easily and rapidly constructed, is rugged, and is adaptable to various applications. When used in a pH-measuring system, drift, pressure artifacts, and flow artifacts are negligible. The response time of the system appears to be less than 10 ms. Using the pH electrode device as described, the dissociation reaction rate constant of H2CO3 at 24 degrees C was determined to be 22 s-1."}
{"id": "PMID:9373", "title": "Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude.", "content": "In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.", "contents": "Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude. In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude."}
{"id": "PMID:9374", "title": "Partial purification and characterization of an endo-alpha-N-acetylgalactosaminidase from the culture of medium of Diplococcus pneumoniae.", "content": "The culture medium of Diplococcus pneumoniae contains enzymic activity that cleaves Galbeta1 leads to 3GalNAc from desialized human erythrocyte membrane glycoprotein. The enzyme was purified 180-fold by ammonium sulfate fractionation, gel filtration through a Sephadex G-200 column, and DEAE A-25 Sephadex chromatography. The purified enzyme liberates Galbeta1 leads to 3GalNAc from glycopeptides and glycoproteins with Galbeta1 leads to 3GalNAcalpha1 leads to Ser and Thr moieties. The optimum pH of this enzyme is 6.0. Using glycopeptides obtained by trypsin digestion of human erythrocyte membrane glycoprotein as a substrate, a Km of 0.20 mM (on the basis of the amount of Galbeta1 leads to 3GalNAc residues) was obtained. So far, the enzyme appears to have a strict specificity for Galbeta1 leads to 3GalNAcalpha1 leads to Ser and Thr structures, because no oligosaccharides larger than trisaccharides were liberated from porcine submaxillary mucin.", "contents": "Partial purification and characterization of an endo-alpha-N-acetylgalactosaminidase from the culture of medium of Diplococcus pneumoniae. The culture medium of Diplococcus pneumoniae contains enzymic activity that cleaves Galbeta1 leads to 3GalNAc from desialized human erythrocyte membrane glycoprotein. The enzyme was purified 180-fold by ammonium sulfate fractionation, gel filtration through a Sephadex G-200 column, and DEAE A-25 Sephadex chromatography. The purified enzyme liberates Galbeta1 leads to 3GalNAc from glycopeptides and glycoproteins with Galbeta1 leads to 3GalNAcalpha1 leads to Ser and Thr moieties. The optimum pH of this enzyme is 6.0. Using glycopeptides obtained by trypsin digestion of human erythrocyte membrane glycoprotein as a substrate, a Km of 0.20 mM (on the basis of the amount of Galbeta1 leads to 3GalNAc residues) was obtained. So far, the enzyme appears to have a strict specificity for Galbeta1 leads to 3GalNAcalpha1 leads to Ser and Thr structures, because no oligosaccharides larger than trisaccharides were liberated from porcine submaxillary mucin."}
{"id": "PMID:9375", "title": "Thiols of myosin. IV. \"Abnormal\" reactivity of S1 thiol and the conformational changes around S2 thiol.", "content": "The flexibility of the tertiary structure around the active site of myosin ATPase [EC 3.6.1.3] was studied using the reactivity of two specific thiol groups, S1 and S2, as a structural probe. The following four maleimide derivatives were used as thiol-directed reagents: N-ethylmaleimide (NEM), N-(4-methoxy-2-benzimidazolyl methyl) maleimide (MBM), N-(p-(2-benzimidazolyl)phenyl)maleimide (BIPM) and N-(4-dimethyl-amino-3,5-dinitrophenyl)maleimide (DDPM). 1. All the maleimide derivatives used activated the Ca2+-ATPase activity and inhibited the EDTA-ATPase activity, like NEM, indicating that they modified S1. The rate of modification of S1 by NEM and BIPM increased with increasing pH, while that by DDPM decreased. BIPM simultaneously modified S1 and S2. 2. S1 showed much higher reactivity toward the maleimides, except for BIPM, than did N-acetylcysteine (N-Ac-Cys) a low molecular-weight model compound. The extremely small pKa value of S1, 6.28, accounted for this high reactivity. In addition, the ATP-induced increase in its reactivity inducated that S1 was in a buried state. Kinetic analysis showed that the teritiary structure around S1 at alkaline pH differed from that at acidic pH. 3. The apparent rate constant of S2-modification with NEM was approximately one seven-hundredth and one four-hundredth of those of S1 and N-Ac-Cys, respectively. Fluorimetric studies using BIPM revealed that S2 in the buried state was exposed upon adding ATP; this was compensated by the burying of some other thiol group(s) (Sp). Non-linearity of the Arrhenius plots of the reaction rate of S2 suggested that the S2 region of myosin had different conformations at high and low temperatures, the transition temperature being 10--15degrees. This non-linearity completely disappeared in the presence of Mg2+-ATP. On the other hand, Arrhenius plots for the thiols reactive to BIPM did not show non-linearity in the presence or absence of ATP.", "contents": "Thiols of myosin. IV. \"Abnormal\" reactivity of S1 thiol and the conformational changes around S2 thiol. The flexibility of the tertiary structure around the active site of myosin ATPase [EC 3.6.1.3] was studied using the reactivity of two specific thiol groups, S1 and S2, as a structural probe. The following four maleimide derivatives were used as thiol-directed reagents: N-ethylmaleimide (NEM), N-(4-methoxy-2-benzimidazolyl methyl) maleimide (MBM), N-(p-(2-benzimidazolyl)phenyl)maleimide (BIPM) and N-(4-dimethyl-amino-3,5-dinitrophenyl)maleimide (DDPM). 1. All the maleimide derivatives used activated the Ca2+-ATPase activity and inhibited the EDTA-ATPase activity, like NEM, indicating that they modified S1. The rate of modification of S1 by NEM and BIPM increased with increasing pH, while that by DDPM decreased. BIPM simultaneously modified S1 and S2. 2. S1 showed much higher reactivity toward the maleimides, except for BIPM, than did N-acetylcysteine (N-Ac-Cys) a low molecular-weight model compound. The extremely small pKa value of S1, 6.28, accounted for this high reactivity. In addition, the ATP-induced increase in its reactivity inducated that S1 was in a buried state. Kinetic analysis showed that the teritiary structure around S1 at alkaline pH differed from that at acidic pH. 3. The apparent rate constant of S2-modification with NEM was approximately one seven-hundredth and one four-hundredth of those of S1 and N-Ac-Cys, respectively. Fluorimetric studies using BIPM revealed that S2 in the buried state was exposed upon adding ATP; this was compensated by the burying of some other thiol group(s) (Sp). Non-linearity of the Arrhenius plots of the reaction rate of S2 suggested that the S2 region of myosin had different conformations at high and low temperatures, the transition temperature being 10--15degrees. This non-linearity completely disappeared in the presence of Mg2+-ATP. On the other hand, Arrhenius plots for the thiols reactive to BIPM did not show non-linearity in the presence or absence of ATP."}
{"id": "PMID:9376", "title": "Stabilization of human serum alkaline phosphatase to histidine-induced heat inactivation by tryptic digestion.", "content": "1. Serum alkaline phosphatase [EC 3.1.3.1] was strongly inactivated by histidine during incubation at pH 8.0 and 45degrees; however, tryptic digestion of the serum strongly protected the enzyme against inactivation by histidine. In the absence of histidine, however, neither heat inactivation of the phosphatase nor the effect of trypsin [EC 3.4.21.4] was observed. Factors affecting the alkaline phosphatase inactivation were studied further. 2. The effect of trypsin on the histidine-induced heat inactivation differed considerably according to the tissue source of the enzyme, which suggests a possible method for distinguishing alkaline phosphatase isoenzymes.", "contents": "Stabilization of human serum alkaline phosphatase to histidine-induced heat inactivation by tryptic digestion. 1. Serum alkaline phosphatase [EC 3.1.3.1] was strongly inactivated by histidine during incubation at pH 8.0 and 45degrees; however, tryptic digestion of the serum strongly protected the enzyme against inactivation by histidine. In the absence of histidine, however, neither heat inactivation of the phosphatase nor the effect of trypsin [EC 3.4.21.4] was observed. Factors affecting the alkaline phosphatase inactivation were studied further. 2. The effect of trypsin on the histidine-induced heat inactivation differed considerably according to the tissue source of the enzyme, which suggests a possible method for distinguishing alkaline phosphatase isoenzymes."}
{"id": "PMID:9377", "title": "Characterization of the NAD+ glycohydrolase associated with the rat liver nuclear envelope.", "content": "The localization of NAD+ glycohydrolase [EC 3.2.2.5] (NADase) in purified rat liver nuclei has been examined. Subnuclear fractionation revealed that at least 70% of the NADase in nuclei was associated with the nuclear envelope fraction. The nuclear envelope fraction was practically free of microsomal contamination as judged by electron microscopic morphometry and assays of microsomal marker enzymes. Therefore, NADase was found to be an integral component of the nuclear envelope. The enzymological properties of the nuclear envelope NADase were compared with those of the microsomal enzyme. The nuclear envelope NADase was identical to the microsomal enzyme in its Km for NAD+ (60 muM), pH optimum (pH 6.5), ratio of transglycosidase activity to NADase activity (about 0.5), thermal stability and sensitivity to various inhibitors. Thus, NADase is a common enzymic component of both the nuclear envelope and the endoplasmic reticulum.", "contents": "Characterization of the NAD+ glycohydrolase associated with the rat liver nuclear envelope. The localization of NAD+ glycohydrolase [EC 3.2.2.5] (NADase) in purified rat liver nuclei has been examined. Subnuclear fractionation revealed that at least 70% of the NADase in nuclei was associated with the nuclear envelope fraction. The nuclear envelope fraction was practically free of microsomal contamination as judged by electron microscopic morphometry and assays of microsomal marker enzymes. Therefore, NADase was found to be an integral component of the nuclear envelope. The enzymological properties of the nuclear envelope NADase were compared with those of the microsomal enzyme. The nuclear envelope NADase was identical to the microsomal enzyme in its Km for NAD+ (60 muM), pH optimum (pH 6.5), ratio of transglycosidase activity to NADase activity (about 0.5), thermal stability and sensitivity to various inhibitors. Thus, NADase is a common enzymic component of both the nuclear envelope and the endoplasmic reticulum."}
{"id": "PMID:9378", "title": "Purification and properties of an alkaline ribonuclease from the hepatic cytosol fraction of bullfrog, Rana catesbeiana.", "content": "In the hepatic cytosol fraction of bullfrog, Rana catesbeiana, an alkaline RNase [EC 3.1.4.22] exists in two forms. One is the free form of RNase, which elutes from a carboxymethyl-cellulose column at a concentration of 0.2 M NaC1. The other is a masked or latent form (RNase-RNase inhibitor complex) which is not adsorbed on the carboxymethyl-cellulose column and which can be converted to the free form of RNase by the addition of p-chloromercuribenzoate. Electrophoretically pure RNase was obtained by the following procedure. The unadsorbed fraction of hepatic cytosol on a column of carboxymethyl-cellulose was treated with p-chloromercuribenzoate and then applied to a second carboxymethyl-cellulose column. The molar weight of RNase was determined to be approximately 12,000 by gel filtration and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. From the results of gel filtration, the molecular weight of the RNase-RNase inhibitor complex was 130,000. The RNase hydrolyzed poly C, poly U, and poly I, but not poly A or poly G. When poly C was used as a substrate, 2',3'-cyclic CMP as an intermediate and 3'-CMP as a final product were identified. The results of amino acid analysis indicated the presence of an unusual component. The general properties of the RNase and the RNase-RNase inhibitor complex are also reported.", "contents": "Purification and properties of an alkaline ribonuclease from the hepatic cytosol fraction of bullfrog, Rana catesbeiana. In the hepatic cytosol fraction of bullfrog, Rana catesbeiana, an alkaline RNase [EC 3.1.4.22] exists in two forms. One is the free form of RNase, which elutes from a carboxymethyl-cellulose column at a concentration of 0.2 M NaC1. The other is a masked or latent form (RNase-RNase inhibitor complex) which is not adsorbed on the carboxymethyl-cellulose column and which can be converted to the free form of RNase by the addition of p-chloromercuribenzoate. Electrophoretically pure RNase was obtained by the following procedure. The unadsorbed fraction of hepatic cytosol on a column of carboxymethyl-cellulose was treated with p-chloromercuribenzoate and then applied to a second carboxymethyl-cellulose column. The molar weight of RNase was determined to be approximately 12,000 by gel filtration and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. From the results of gel filtration, the molecular weight of the RNase-RNase inhibitor complex was 130,000. The RNase hydrolyzed poly C, poly U, and poly I, but not poly A or poly G. When poly C was used as a substrate, 2',3'-cyclic CMP as an intermediate and 3'-CMP as a final product were identified. The results of amino acid analysis indicated the presence of an unusual component. The general properties of the RNase and the RNase-RNase inhibitor complex are also reported."}
{"id": "PMID:9379", "title": "Enzymatic synthesis of oligonucleotides of defined sequence. The \"single addition\" of 2(3)-O-dihydrocinnamoyl-nucleoside 5'-diphosphate to a primer oligonucleotide catalyzed by a thermophilic polynucleotide phosphorylase.", "content": "Several oligonucleotides of defined sequence were synthesized using 2'(3')-O-dihydrocinnamoyl-nucleoside 5'-diphosphates (DHC-NDP) as substrates for polynucleotide phosphorylase [EC 2.7.7.8] from Thermus thermophilus. The enzyme catalyzed the transfer of one nucleotidyl residue from each of the 2'(3')-O-dihydrocinnamoyl esters of CDP, UDP, and GDP to the 3'-terminus of the primer triadenosine diphosphate, (Ap)2A. The products were shown to be (Ap)3C, (Ap)3U, and (Ap)3G by enzymatic analysis.", "contents": "Enzymatic synthesis of oligonucleotides of defined sequence. The \"single addition\" of 2(3)-O-dihydrocinnamoyl-nucleoside 5'-diphosphate to a primer oligonucleotide catalyzed by a thermophilic polynucleotide phosphorylase. Several oligonucleotides of defined sequence were synthesized using 2'(3')-O-dihydrocinnamoyl-nucleoside 5'-diphosphates (DHC-NDP) as substrates for polynucleotide phosphorylase [EC 2.7.7.8] from Thermus thermophilus. The enzyme catalyzed the transfer of one nucleotidyl residue from each of the 2'(3')-O-dihydrocinnamoyl esters of CDP, UDP, and GDP to the 3'-terminus of the primer triadenosine diphosphate, (Ap)2A. The products were shown to be (Ap)3C, (Ap)3U, and (Ap)3G by enzymatic analysis."}
{"id": "PMID:9380", "title": "Incorporation of serine and ethanolamine into the phospholipids in rabbit retina.", "content": "The incorporation of serine and ethanolamine into phospholipids in rabbit retinal subcellular fractions and in excised retinas was studied in vitro, and some enzymic properties of the incorporation of phospholipid bases by base exchange were examined in the microsomal fraction. The retina was found to have a higher rate of base exchange for the incorporation of phospholipid bases than other tissues. The retinal microsomal fraction possessed the highest specific activity of base exchange, while the rod outer segment had very little activity. These results suggest that the phospholipids in the rod outer segment may be transferred from the inner segment of the photorecepter cell. The apparent Km values for serine and ethanolamine in the microsomal fraction decreased with decreasing Ca2+ concentration. Although no further increase of incorporation of serine and ethanolamine occurred after 40 min in the microsomal fraction, continuous incorporation of both bases into phospholipids was seen for 3 hr in excised retina. Illumination did not significantly affect the incorporation of serine and ethanolamine in excised retina or in the rod outer segment fraction. Base exchange reaction thus may not play a direct role in the visual process.", "contents": "Incorporation of serine and ethanolamine into the phospholipids in rabbit retina. The incorporation of serine and ethanolamine into phospholipids in rabbit retinal subcellular fractions and in excised retinas was studied in vitro, and some enzymic properties of the incorporation of phospholipid bases by base exchange were examined in the microsomal fraction. The retina was found to have a higher rate of base exchange for the incorporation of phospholipid bases than other tissues. The retinal microsomal fraction possessed the highest specific activity of base exchange, while the rod outer segment had very little activity. These results suggest that the phospholipids in the rod outer segment may be transferred from the inner segment of the photorecepter cell. The apparent Km values for serine and ethanolamine in the microsomal fraction decreased with decreasing Ca2+ concentration. Although no further increase of incorporation of serine and ethanolamine occurred after 40 min in the microsomal fraction, continuous incorporation of both bases into phospholipids was seen for 3 hr in excised retina. Illumination did not significantly affect the incorporation of serine and ethanolamine in excised retina or in the rod outer segment fraction. Base exchange reaction thus may not play a direct role in the visual process."}
{"id": "PMID:9381", "title": "The structure and function of acid proteases. IV. Inactivation of the acid protease from Mucor pusillus by acid protease-specific inhibitors.", "content": "Mucor pusillus acid protease was rapidly inactivated with 1 : 1 stoichiometry by reaction with diazoacetyl-DL-norleucine methyl ester (DAN) in the presence of cupric ions. Cupric ions were essential for this inactivation. The rate of inactivation was maximal at around pH 6 when the enzyme was mixed with DAN and cupric ions without prior mixing of the reagents, and at pH 5.3 when DAN and cupric ions were mixed and incubated before addition to the enzyme solution. In both cases, the rate of inactivation decreased as the pH was either increased or decreased. The amino acid composition of an acid hydrolysate of the DAN-Modified enzyme was indistinguishable from that of the native enzyme except for the incorporation of about one norleucine residue per molecule of protein. The enzyme was also inactivated by reaction with 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP). At the stage of about 90% inactivation, 1.50 residues of EPNP were incorporated per molecule of protein and the rate of inactivation followed pseudo-first order kinetics. The optimal pH for the inactivation was pH 3.0 and the rate of inactivation decreased as the pH was either increased or decreased. Furthermore, the enzyme was strongly inhibited by pepstatin, and the reactions of DAN and of EPNP was also inhibited significantly by prior treatment of the enzyme with pepstatin. These results suggest that the enzyme may have two essential carboxyl groups at the active site, one reactive with DAN in the presence of cupric ions and the other with EPNP, and that pepstatin binds part of the active site to inhibit the reactions with DAN and EPNP as well as the enzyme activity.", "contents": "The structure and function of acid proteases. IV. Inactivation of the acid protease from Mucor pusillus by acid protease-specific inhibitors. Mucor pusillus acid protease was rapidly inactivated with 1 : 1 stoichiometry by reaction with diazoacetyl-DL-norleucine methyl ester (DAN) in the presence of cupric ions. Cupric ions were essential for this inactivation. The rate of inactivation was maximal at around pH 6 when the enzyme was mixed with DAN and cupric ions without prior mixing of the reagents, and at pH 5.3 when DAN and cupric ions were mixed and incubated before addition to the enzyme solution. In both cases, the rate of inactivation decreased as the pH was either increased or decreased. The amino acid composition of an acid hydrolysate of the DAN-Modified enzyme was indistinguishable from that of the native enzyme except for the incorporation of about one norleucine residue per molecule of protein. The enzyme was also inactivated by reaction with 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP). At the stage of about 90% inactivation, 1.50 residues of EPNP were incorporated per molecule of protein and the rate of inactivation followed pseudo-first order kinetics. The optimal pH for the inactivation was pH 3.0 and the rate of inactivation decreased as the pH was either increased or decreased. Furthermore, the enzyme was strongly inhibited by pepstatin, and the reactions of DAN and of EPNP was also inhibited significantly by prior treatment of the enzyme with pepstatin. These results suggest that the enzyme may have two essential carboxyl groups at the active site, one reactive with DAN in the presence of cupric ions and the other with EPNP, and that pepstatin binds part of the active site to inhibit the reactions with DAN and EPNP as well as the enzyme activity."}
{"id": "PMID:9382", "title": "Purification and properties of an enzyme catalyzing the splitting of carbon-mercury linkages from mercury-resistant Pseudomonas K-62 strain. I. Splitting enzyme 1.", "content": "An enzyme (S-1) which catalyzes the splitting of carbon-mercury linkages of organomercury compounds was purified about 24-fold from the cell-free extract of mercury-resistant Pseudomonas K-62 strain by treatment with streptomycin, precipitation with ammonium sulfate, and successive chromatography on Sephadex G-150, DEAE-Sephadex, and DEAE-cellulose. A purified preparation of the enzyme showed a single band on polyacrylamide gel electrophoresis, and was colorless. The molecular weight of the enzyme was estimated to be 19,000, and Km was 5.3 X 10(-5) M for p-chloromercuribenzoic acid (PCMB). The temperature and pH optimum for the reaction were 50degrees and 7.0, respectively. The enzyme was capable of catalyzing the decomposition of methylmercuric chloride (MMC), ethylmercuric chloride (EMC), phenylmercuric acetate (PMA), and PCMB in the presence of a sulfhydryl compound to form a mercuric ion plus methane, ethane, benzene, or benzoic acid, respectively. The mercuric ion thus formed was reduced to metallic mercury by metallic mercury-releasing enzyme (MMR-enzyme).", "contents": "Purification and properties of an enzyme catalyzing the splitting of carbon-mercury linkages from mercury-resistant Pseudomonas K-62 strain. I. Splitting enzyme 1. An enzyme (S-1) which catalyzes the splitting of carbon-mercury linkages of organomercury compounds was purified about 24-fold from the cell-free extract of mercury-resistant Pseudomonas K-62 strain by treatment with streptomycin, precipitation with ammonium sulfate, and successive chromatography on Sephadex G-150, DEAE-Sephadex, and DEAE-cellulose. A purified preparation of the enzyme showed a single band on polyacrylamide gel electrophoresis, and was colorless. The molecular weight of the enzyme was estimated to be 19,000, and Km was 5.3 X 10(-5) M for p-chloromercuribenzoic acid (PCMB). The temperature and pH optimum for the reaction were 50degrees and 7.0, respectively. The enzyme was capable of catalyzing the decomposition of methylmercuric chloride (MMC), ethylmercuric chloride (EMC), phenylmercuric acetate (PMA), and PCMB in the presence of a sulfhydryl compound to form a mercuric ion plus methane, ethane, benzene, or benzoic acid, respectively. The mercuric ion thus formed was reduced to metallic mercury by metallic mercury-releasing enzyme (MMR-enzyme)."}
{"id": "PMID:9383", "title": "Interaction of tropomyosin with troponin components.", "content": "1. The TN-T and TN-I components of troponin both interact with tropomyosin and cause its precipitation in 0.1 M KC1 at neutral pH. The precipitate contains both end-to-end and side-by-side aggregates of tropomyosin molecules. 2. The TN-T and TN-I components change the band pattern of tropomyosin paracrystals formed in MgC1(2) solutions, although in different ways. TN-T causes the formation of hexagonal net structures, double-stranded net or paracrystals which result from the collapse of the double-stranded net. TN-I at pH 7.9 causes the formation of paracrystals with a 400 A periodic band pattern and a 200 A repeat. The same band pattern can also be seen in tropomyosin paracrystals formed at pH values below 6.0. 3. The TN-C component does not precipitate tropomyosin in 0.1 M KC1. The aggregates of tropomyosin obtained with either TN-T or TN-I can be solubilized by the addition of TN-C. No interaction of TN-C was observed with tropomyosin paracrystals formed in the presence of MgC12.", "contents": "Interaction of tropomyosin with troponin components. 1. The TN-T and TN-I components of troponin both interact with tropomyosin and cause its precipitation in 0.1 M KC1 at neutral pH. The precipitate contains both end-to-end and side-by-side aggregates of tropomyosin molecules. 2. The TN-T and TN-I components change the band pattern of tropomyosin paracrystals formed in MgC1(2) solutions, although in different ways. TN-T causes the formation of hexagonal net structures, double-stranded net or paracrystals which result from the collapse of the double-stranded net. TN-I at pH 7.9 causes the formation of paracrystals with a 400 A periodic band pattern and a 200 A repeat. The same band pattern can also be seen in tropomyosin paracrystals formed at pH values below 6.0. 3. The TN-C component does not precipitate tropomyosin in 0.1 M KC1. The aggregates of tropomyosin obtained with either TN-T or TN-I can be solubilized by the addition of TN-C. No interaction of TN-C was observed with tropomyosin paracrystals formed in the presence of MgC12."}
{"id": "PMID:9384", "title": "Purification and characterization of beta-N-acetylhexosaminidases and beta-galactosidase from Streptococcus 6646 K.", "content": "Three beta-N-acetylhexosaminidases [EC 3.2.1.52] and one beta-galactosidase [EC 3.2.1.23] were purified from the culture filtrate of streptococcus 6646 group K by a combination of column chromatographies on p-aminophenyl beta-D-thiogalactopyranoside-substituted Sepharose and N-(paminophenyl)oxamic acid-substituted Sepharose. These beta-N-acetylhexosaminidases showed optimal activities between pH 5.0 and 5.5 and could hydrolyze synthetic and glycopeptidic substrates. Glycolipids such as GM2, asialo-GM2, and globoside I were no susceptible to these beta-hexosaminidases. beta-Galactosidase, which was purified more than 11,000-fold, had a substrate specificity rather similar to that of beta-galactosidase from E. coli. This enzyme was inhibited by EDTA and activated by Mn2+, Ca2+, and Mg2+. Problems pertinent to the application of affinity chromatography to the purification of glycosidases are also discussed.", "contents": "Purification and characterization of beta-N-acetylhexosaminidases and beta-galactosidase from Streptococcus 6646 K. Three beta-N-acetylhexosaminidases [EC 3.2.1.52] and one beta-galactosidase [EC 3.2.1.23] were purified from the culture filtrate of streptococcus 6646 group K by a combination of column chromatographies on p-aminophenyl beta-D-thiogalactopyranoside-substituted Sepharose and N-(paminophenyl)oxamic acid-substituted Sepharose. These beta-N-acetylhexosaminidases showed optimal activities between pH 5.0 and 5.5 and could hydrolyze synthetic and glycopeptidic substrates. Glycolipids such as GM2, asialo-GM2, and globoside I were no susceptible to these beta-hexosaminidases. beta-Galactosidase, which was purified more than 11,000-fold, had a substrate specificity rather similar to that of beta-galactosidase from E. coli. This enzyme was inhibited by EDTA and activated by Mn2+, Ca2+, and Mg2+. Problems pertinent to the application of affinity chromatography to the purification of glycosidases are also discussed."}
{"id": "PMID:9385", "title": "On the mechanism of action of oligomycin and acidic uncouplers on proton translocation and energy transfer in \"sonic\" submitochondrial particles.", "content": "A study is presented of the effect of acidic uncouplers and oligomycin on energy-linked and passive proton translocation, oxidative phosphorylation, and energy-linked nicotinamide-adenine-nucleotide transhydrogenase in EDTA submitochondrial particles from beef-heart. A flow potentiometric technique has been applied to resolve the kinetics of the initial rapid phase of the redox proton pump. Rapid kinetics analysis shows that carbonyl-cyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP) does not exert any direct effect on redox-linked active proton transport. The uncoupling action of FCCP on oxidative phosphorylation and energy-linked transhydrogenase is shown to be quantitatively accounted for by its promoting effect of passive proton-diffusion across the mitochondrial membrane. Oligomycin depresses passive proton diffusion in EDTA sonic particles and this effect accounts for the coupling action exerted by the antibiotic on oxidative phosphorylation and energy-linked transhydrogenase. In fact, rapid kinetic analysis demonstrates that oligomycin does not directly affect the redox-linked proton pump. The present results show that there does not exist any labile intermediate in the redox-linked proton pump which is sensitive to acidic uncouplers.", "contents": "On the mechanism of action of oligomycin and acidic uncouplers on proton translocation and energy transfer in \"sonic\" submitochondrial particles. A study is presented of the effect of acidic uncouplers and oligomycin on energy-linked and passive proton translocation, oxidative phosphorylation, and energy-linked nicotinamide-adenine-nucleotide transhydrogenase in EDTA submitochondrial particles from beef-heart. A flow potentiometric technique has been applied to resolve the kinetics of the initial rapid phase of the redox proton pump. Rapid kinetics analysis shows that carbonyl-cyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP) does not exert any direct effect on redox-linked active proton transport. The uncoupling action of FCCP on oxidative phosphorylation and energy-linked transhydrogenase is shown to be quantitatively accounted for by its promoting effect of passive proton-diffusion across the mitochondrial membrane. Oligomycin depresses passive proton diffusion in EDTA sonic particles and this effect accounts for the coupling action exerted by the antibiotic on oxidative phosphorylation and energy-linked transhydrogenase. In fact, rapid kinetic analysis demonstrates that oligomycin does not directly affect the redox-linked proton pump. The present results show that there does not exist any labile intermediate in the redox-linked proton pump which is sensitive to acidic uncouplers."}
{"id": "PMID:9387", "title": "3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase. Purification, properties, and kinetics of the tyrosine-sensitive isoenzyme from Escherichia coli.", "content": "The tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate lyase (pyruvate-phosphorylating), EC 4.2.1.15) was purified to homogeneity from extracts of Escherichia coli K12. A spectrophotometric assay of the enzyme activity, based on the absorption difference of substrates and products at 232 nm, was developed. The enzyme has a molecular weight of 66,000 as judged by gel filtration on Sephadex G-200, and a subunit molecular weight of 39,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. This suggests either a rapid monomer-dimer equilibrium, or a very asymmetric shape for the native enzyme. The enzyme shows a narrow pH optimum around pH 7.0. The enzyme is stable for several months when stored at -20 degrees in phosphate buffer containing phosphoenol-pyruvate. Intersecting lines in double reciprocal plots of initial velocity data at substrate concentrations in the micromolar range suggest a sequential mechanism with-catalyzed reaction. Product inhibition studies specify an ordered sequential BiBi mechanism with a dead-end E-P complex. The feedback inhibitor tyrosine at concentrations above 10 muM exhibits noncompetitive inhibition with respect to erythrose-4-P, and competitive inhibition with respect to the other substrate, P-enolpyruvate. In addition, tyrosine at concentrations of at least 10 muM causes an alteration of one or more than one kinetic parameter of the enzyme.", "contents": "3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase. Purification, properties, and kinetics of the tyrosine-sensitive isoenzyme from Escherichia coli. The tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate lyase (pyruvate-phosphorylating), EC 4.2.1.15) was purified to homogeneity from extracts of Escherichia coli K12. A spectrophotometric assay of the enzyme activity, based on the absorption difference of substrates and products at 232 nm, was developed. The enzyme has a molecular weight of 66,000 as judged by gel filtration on Sephadex G-200, and a subunit molecular weight of 39,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. This suggests either a rapid monomer-dimer equilibrium, or a very asymmetric shape for the native enzyme. The enzyme shows a narrow pH optimum around pH 7.0. The enzyme is stable for several months when stored at -20 degrees in phosphate buffer containing phosphoenol-pyruvate. Intersecting lines in double reciprocal plots of initial velocity data at substrate concentrations in the micromolar range suggest a sequential mechanism with-catalyzed reaction. Product inhibition studies specify an ordered sequential BiBi mechanism with a dead-end E-P complex. The feedback inhibitor tyrosine at concentrations above 10 muM exhibits noncompetitive inhibition with respect to erythrose-4-P, and competitive inhibition with respect to the other substrate, P-enolpyruvate. In addition, tyrosine at concentrations of at least 10 muM causes an alteration of one or more than one kinetic parameter of the enzyme."}
{"id": "PMID:9388", "title": "Human adenosine deaminase. Distribution and properties.", "content": "Adenosine deaminase exists in multiple molecular forms in human tissue. One form of the enzyme appears to be \"particulate\". Three forms of the enzyme are soluble and interconvertible with apparent molecular weights of approximately 36,000, 114,000, and 298,000 (designated small, intermediate, and large, respectively). The small form of adenosine deaminase is convertible to the large form only in the presence of a protein, which has an apparent molecular weight of 200,000 and has no adenosine deaminase activity. This conversion of the small form of the enzyme to the large form occurs at 4 degrees, exhibits a pH optimum of 5.0 to 8.0, and is associated with a loss of conversion activity. The small form of the enzyme predominates in tissue preparations exhibiting the higher enzyme-specific activities and no detectable conversion activity. The large form of adenosine deaminase predominates in tissue extracts exhibiting the lower enzyme specific activities and abundant conversion activity. The small form of adenosine deaminase shows several electrophoretic variants by isoelectric focusing. The electrophoretic heterogeneity observed with the large form of the enzyme is similar to that observed with the small form, with the exception that several additional electrophoretic variants are uniformly identified. No organ specificity is demonstrable for the different electrophoretic forms. The kinetic characteristics of the three soluble molecular species of adenosine deaminase are identical except for pH optimum, which is 5.5 for the intermediate species and 7.0 to 7.4 for the large and small forms.", "contents": "Human adenosine deaminase. Distribution and properties. Adenosine deaminase exists in multiple molecular forms in human tissue. One form of the enzyme appears to be \"particulate\". Three forms of the enzyme are soluble and interconvertible with apparent molecular weights of approximately 36,000, 114,000, and 298,000 (designated small, intermediate, and large, respectively). The small form of adenosine deaminase is convertible to the large form only in the presence of a protein, which has an apparent molecular weight of 200,000 and has no adenosine deaminase activity. This conversion of the small form of the enzyme to the large form occurs at 4 degrees, exhibits a pH optimum of 5.0 to 8.0, and is associated with a loss of conversion activity. The small form of the enzyme predominates in tissue preparations exhibiting the higher enzyme-specific activities and no detectable conversion activity. The large form of adenosine deaminase predominates in tissue extracts exhibiting the lower enzyme specific activities and abundant conversion activity. The small form of adenosine deaminase shows several electrophoretic variants by isoelectric focusing. The electrophoretic heterogeneity observed with the large form of the enzyme is similar to that observed with the small form, with the exception that several additional electrophoretic variants are uniformly identified. No organ specificity is demonstrable for the different electrophoretic forms. The kinetic characteristics of the three soluble molecular species of adenosine deaminase are identical except for pH optimum, which is 5.5 for the intermediate species and 7.0 to 7.4 for the large and small forms."}
{"id": "PMID:9389", "title": "Electron paramagnetic resonance of the tungsten derivative of rat liver sulfite oxidase.", "content": "Sulfite oxidase purified from livers of tungsten-treated rats has been used for EPR studies of tungsten substituted at the molybdenum site of the enzyme in a fraction of the molecules. The EPR signal of W(V) in sulfite oxidase is quite similar to that of Mo(V) in its line shape and in its sensitivity to the presence of anions such as phosphate and fluoride. Hyperfine interaction with a dissociable proton is also observed in both signals. The pH-dependent alteration in line shape exhibited by the Mo(V) EPR signal of the rat liver enzyme. Incomplete reduction of the tungsten center at pH 9 is indicated by attenuated signal intensity at this pH. The W(V) signal has g values lower than those of the Mo(V) signal, has a much broader resonance envelope, and is much less readily saturated by increasing microwave power. Kinetic studies on the reduction of the heme and tungsten centers of sulfite oxidase have shown that reduction of de-molybdo forms of sulfite oxidase by sulfite is catalyzed by the residual traces of native molybdenum-containing molecules. Reduction is accomplished by electron transfer involving intermolecular heme-heme interaction. The W(V) signal is generated only after all the heme centers are reduced. The rate and extent of heme reduction at pH 9 are the same as at pH 7. Studies on the reoxidation of W(V) and reduced heme by O2 and by cytochrome c suggest that the cytochrome b5 of sulfite oxidase is the site of electron transfer to cytochrome c, whereas oxidase activity is the property of the molybdenum center. It appears that the tungsten center in sulfite oxidase is incapable of oxidizing sulfite.", "contents": "Electron paramagnetic resonance of the tungsten derivative of rat liver sulfite oxidase. Sulfite oxidase purified from livers of tungsten-treated rats has been used for EPR studies of tungsten substituted at the molybdenum site of the enzyme in a fraction of the molecules. The EPR signal of W(V) in sulfite oxidase is quite similar to that of Mo(V) in its line shape and in its sensitivity to the presence of anions such as phosphate and fluoride. Hyperfine interaction with a dissociable proton is also observed in both signals. The pH-dependent alteration in line shape exhibited by the Mo(V) EPR signal of the rat liver enzyme. Incomplete reduction of the tungsten center at pH 9 is indicated by attenuated signal intensity at this pH. The W(V) signal has g values lower than those of the Mo(V) signal, has a much broader resonance envelope, and is much less readily saturated by increasing microwave power. Kinetic studies on the reduction of the heme and tungsten centers of sulfite oxidase have shown that reduction of de-molybdo forms of sulfite oxidase by sulfite is catalyzed by the residual traces of native molybdenum-containing molecules. Reduction is accomplished by electron transfer involving intermolecular heme-heme interaction. The W(V) signal is generated only after all the heme centers are reduced. The rate and extent of heme reduction at pH 9 are the same as at pH 7. Studies on the reoxidation of W(V) and reduced heme by O2 and by cytochrome c suggest that the cytochrome b5 of sulfite oxidase is the site of electron transfer to cytochrome c, whereas oxidase activity is the property of the molybdenum center. It appears that the tungsten center in sulfite oxidase is incapable of oxidizing sulfite."}
{"id": "PMID:9390", "title": "Tetramer-dimer dissociation in homoglobin and the Bohr effect.", "content": "The pH dependence of the apparent tetramer to dimer dissociation constant has been determined at 20 degrees for both oxy- and deoxyhemoglobins A and Kansas. These measurements were made by three different procedures: gel chromatography, sedimentation velocity, and kinetic methods in either of three buffer systems: 0.05 M cacodylate, Tris, or glycine with 1 mM EDTA and 0.1 M NaCl between pH 6.5 and 11. The tetramer-dimer dissociation constant of human oxyhemoglobin A decreases from about 3.2 X 10(-6) M at pH 6.0 to about 3.2 X 10(-8) M at pH 8.5. The slope of this line indicates that the dissociation of tetramer to dimer is accompanied by the uptake of about 0.6 protons per mol of tetramer in this region. The corresponding dissociation constant for deoxyhemoglobin in the same pH region increases apparently almost linearly from 1.0 x 10(-12) M at pH 6.5 to about 1.0 x 10(-5) M at pH 11. To dimer is associated with the release of about 1.6 protons per mol of tetramer. Comparison of these data with the known proton release accompanying the oxygenation of tetramers confirms that the pH dependence of oxygen binding by dimers must be very small. The present data predict that the overall proton release or uptake per oxygen bound by dimer should be less than 0.1. The tetramer-dimer dissociation equilibria of oxy- and deoxyhemoglobins above pH 8.5 have identical pH dependences. In this range the dissociation constant of deoxy-Hb is about one-tenth that of oxyhemoglobin. Human oxyhemoglobin Kansas is known to have an enhanced tetramer-dimer dissociation compared with that of hemoglobin A. Below pH 8.5 the tetramer-dimer dissociation constant of Hb Kansas is about 400 times greater than that of HbA in the absence of phosphate buffers. In contrast, the tetramer-dimer dissociation constants of deoxyhemoglobins A and Kansas appear to be identical. These findings are consistent with previous structural observations on these hemoglobins. The data on the tetramer-dimer dissociation of human hemoglobin were used to calculate the total free energy of binding of oxygen to the tetramer and the median oxygen pressure on the basis of fundamental linkage relations and a pH-independent estimate of the total free energy of binding oxygen to dimer. Simulated oxygen binding curves were generated with the equations of Ackers and Halvorson (Ackers, G. K., and Halvorson, H. (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 4312-4316) by making two assumptions: (a) that the dimers are noncooperative and pH-independent in O2 binding and (b) that the distribution of cooperative energy in the oxygenation of tetramers is independent of pH. We have compared these simulations with experimental data obtained at low protein concentrations (30 to 124 muM heme) to show that the variation in oxygen affinity with pH can be described in terms of the subunit equilibria. We conclude that an accurate analysis of the contributions of individual oxygen binding steps to the Bohr effect cannot be made without considering the contributions of the dimers to oxygen binding...", "contents": "Tetramer-dimer dissociation in homoglobin and the Bohr effect. The pH dependence of the apparent tetramer to dimer dissociation constant has been determined at 20 degrees for both oxy- and deoxyhemoglobins A and Kansas. These measurements were made by three different procedures: gel chromatography, sedimentation velocity, and kinetic methods in either of three buffer systems: 0.05 M cacodylate, Tris, or glycine with 1 mM EDTA and 0.1 M NaCl between pH 6.5 and 11. The tetramer-dimer dissociation constant of human oxyhemoglobin A decreases from about 3.2 X 10(-6) M at pH 6.0 to about 3.2 X 10(-8) M at pH 8.5. The slope of this line indicates that the dissociation of tetramer to dimer is accompanied by the uptake of about 0.6 protons per mol of tetramer in this region. The corresponding dissociation constant for deoxyhemoglobin in the same pH region increases apparently almost linearly from 1.0 x 10(-12) M at pH 6.5 to about 1.0 x 10(-5) M at pH 11. To dimer is associated with the release of about 1.6 protons per mol of tetramer. Comparison of these data with the known proton release accompanying the oxygenation of tetramers confirms that the pH dependence of oxygen binding by dimers must be very small. The present data predict that the overall proton release or uptake per oxygen bound by dimer should be less than 0.1. The tetramer-dimer dissociation equilibria of oxy- and deoxyhemoglobins above pH 8.5 have identical pH dependences. In this range the dissociation constant of deoxy-Hb is about one-tenth that of oxyhemoglobin. Human oxyhemoglobin Kansas is known to have an enhanced tetramer-dimer dissociation compared with that of hemoglobin A. Below pH 8.5 the tetramer-dimer dissociation constant of Hb Kansas is about 400 times greater than that of HbA in the absence of phosphate buffers. In contrast, the tetramer-dimer dissociation constants of deoxyhemoglobins A and Kansas appear to be identical. These findings are consistent with previous structural observations on these hemoglobins. The data on the tetramer-dimer dissociation of human hemoglobin were used to calculate the total free energy of binding of oxygen to the tetramer and the median oxygen pressure on the basis of fundamental linkage relations and a pH-independent estimate of the total free energy of binding oxygen to dimer. Simulated oxygen binding curves were generated with the equations of Ackers and Halvorson (Ackers, G. K., and Halvorson, H. (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 4312-4316) by making two assumptions: (a) that the dimers are noncooperative and pH-independent in O2 binding and (b) that the distribution of cooperative energy in the oxygenation of tetramers is independent of pH. We have compared these simulations with experimental data obtained at low protein concentrations (30 to 124 muM heme) to show that the variation in oxygen affinity with pH can be described in terms of the subunit equilibria. We conclude that an accurate analysis of the contributions of individual oxygen binding steps to the Bohr effect cannot be made without considering the contributions of the dimers to oxygen binding..."}
{"id": "PMID:9391", "title": "Rapid transfer of oxygens from inorganic phosphate to glutamine catalyzed by Escherichia coli glutamine synthetase.", "content": "Measurements are reported on certain isotopic fluxes during the net conversion of glutamine, ADP and Pi to glutamate, NH3, and ATP by Escherichia coli glutamine synthetase (adenylylated form, Mn2+ activated) in presence of a hexokinase/glucose trap to remove the ATP formed during the reaction. The results show that the transfer of oxygens from Pi to glutamine is the most rapid of the measured isotopic interchanges, over five oxygens from Pi being transferred to glutamine for each glutamate formed by net reaction. Under similar conditions, the oxygen transfer from Pi to glutamate, was stimulated somewhat by an increase in the glutamate concentration but inhibited by an increase in the ammonia concentration. The enzyme from brain or peas did not show the rapid transfer of 18O from Pi to glutamine shown by the E. coli enzyme. Deductions are also made from the data about the availability of the oxygens of gamma-carboxyl of bound glutamate for reaction. The most logical explanation of the results with the E. coli enzyme is that the gamma-carboxyl group of bound glutamate has sufficient rotational freedom so that under conditions of rapid substrate interconversion either carboxylate oxygen can participate in the reaction. The results with the pea enzyme are consistent with hindered rotation of the gamma-care additional findings make likely a relative order of certain catalytic steps for the E. coli enzyme as follows: ATP release less than NH3 release less than glutamate release less than substrate interconversion less than glutamine release and Pi release and glutamate release less than ADP release.", "contents": "Rapid transfer of oxygens from inorganic phosphate to glutamine catalyzed by Escherichia coli glutamine synthetase. Measurements are reported on certain isotopic fluxes during the net conversion of glutamine, ADP and Pi to glutamate, NH3, and ATP by Escherichia coli glutamine synthetase (adenylylated form, Mn2+ activated) in presence of a hexokinase/glucose trap to remove the ATP formed during the reaction. The results show that the transfer of oxygens from Pi to glutamine is the most rapid of the measured isotopic interchanges, over five oxygens from Pi being transferred to glutamine for each glutamate formed by net reaction. Under similar conditions, the oxygen transfer from Pi to glutamate, was stimulated somewhat by an increase in the glutamate concentration but inhibited by an increase in the ammonia concentration. The enzyme from brain or peas did not show the rapid transfer of 18O from Pi to glutamine shown by the E. coli enzyme. Deductions are also made from the data about the availability of the oxygens of gamma-carboxyl of bound glutamate for reaction. The most logical explanation of the results with the E. coli enzyme is that the gamma-carboxyl group of bound glutamate has sufficient rotational freedom so that under conditions of rapid substrate interconversion either carboxylate oxygen can participate in the reaction. The results with the pea enzyme are consistent with hindered rotation of the gamma-care additional findings make likely a relative order of certain catalytic steps for the E. coli enzyme as follows: ATP release less than NH3 release less than glutamate release less than substrate interconversion less than glutamine release and Pi release and glutamate release less than ADP release."}
{"id": "PMID:9392", "title": "ATP-dependent calcium transport in isolated membrane vesicles from Azotobacter vinelandii.", "content": "Membrane vesicles from Azotobacter vinelandii O prepared by osmotic lysis of spheroplasts in tris (hydroxymethyl) aminomethane/acetate buffer (pH 7.8) contain a latent adenosine triphosphatase (ATPase). The ATPase can be activated when the vesicles are incubated in the presence of an electron donor (D-lactate) and a mixture of adenosine diphosphate and inorganic phosphate or by controlled treatment with trypsin. After the ATPase is activated, the membrane vesicles in the presence of adenosine triphosphate accumulate calcium but not glucose or rubidium (in the presence of valinomycin). ATP-dependent calcium uptake follows Michaelis-Menten kinetics with a Km of 48 muM and a Vmax of 20 nmol/min/mg of membrane protein and is highly specific for calcium over cations magnesium, barium, lanthanum, sodium, potassium, and lithium. The calcium accumulated in the presence of ATP is freely exchangeable with external calcium and is rapidly released in the presenceof uncouplers or ATPase inhibitors. Calcium uptake in the presenceof ATP is blocked by dicyclohexylcarbodiimide, ADP, p-chloromercuriphenylsulfonate, by the proton-conducting ionophores m-chlorophenylcarbonylcyanide hydrazone, nigericin, monensin, and gramicidin D, but not by potassium cyanide, anoxia, or valinomycin (in the presence of potassium). Measurements of the external pH of vesicle suspensions reveal that protons are actively taken up by the membranes during hydrolysis of ATP. These results suggest that vesicles prepared under these conditions have a topology which is inverted with respect to the intact cell and that calcium is accumulated by means of proton antiport.", "contents": "ATP-dependent calcium transport in isolated membrane vesicles from Azotobacter vinelandii. Membrane vesicles from Azotobacter vinelandii O prepared by osmotic lysis of spheroplasts in tris (hydroxymethyl) aminomethane/acetate buffer (pH 7.8) contain a latent adenosine triphosphatase (ATPase). The ATPase can be activated when the vesicles are incubated in the presence of an electron donor (D-lactate) and a mixture of adenosine diphosphate and inorganic phosphate or by controlled treatment with trypsin. After the ATPase is activated, the membrane vesicles in the presence of adenosine triphosphate accumulate calcium but not glucose or rubidium (in the presence of valinomycin). ATP-dependent calcium uptake follows Michaelis-Menten kinetics with a Km of 48 muM and a Vmax of 20 nmol/min/mg of membrane protein and is highly specific for calcium over cations magnesium, barium, lanthanum, sodium, potassium, and lithium. The calcium accumulated in the presence of ATP is freely exchangeable with external calcium and is rapidly released in the presenceof uncouplers or ATPase inhibitors. Calcium uptake in the presenceof ATP is blocked by dicyclohexylcarbodiimide, ADP, p-chloromercuriphenylsulfonate, by the proton-conducting ionophores m-chlorophenylcarbonylcyanide hydrazone, nigericin, monensin, and gramicidin D, but not by potassium cyanide, anoxia, or valinomycin (in the presence of potassium). Measurements of the external pH of vesicle suspensions reveal that protons are actively taken up by the membranes during hydrolysis of ATP. These results suggest that vesicles prepared under these conditions have a topology which is inverted with respect to the intact cell and that calcium is accumulated by means of proton antiport."}
{"id": "PMID:9393", "title": "Phosphofructokinase. I. Mechanism of the pH-dependent inactivation and reactivation of the rabbit muscle enzyme.", "content": "The kinetics of inactivation and reactivation of rabbit skeletal muscle phosphofructokinase have been studied as a function of pH and enzyme concentration at constant temperature in phosphate buffer. From the enzyme concentration dependence, we conclude that the minimal mechanism for inactivation involves a protonation step followed by isomerization to an inactive form and then dissociation to a species of one-half the molecular weight. Other data indicate a subsequent isomerization of the dissociated form. The pH and temperature dependence of the inactivation process shows that it is controlled by ionizable groups, and that the apparent pK for these groups is temperature-dependent in such a way as to make the enzyme show the characteristic of cold lability below pH 7. Reactivation of the inactive enzyme occurs by a kinetically different pathway involving deprotonation of an inactive, dissociated form to a form which may either isomerize to another inactive form, or dimerize to the active enzyme. A general mechanism is postulated in which the inactivation and reactivation processes are different aspects of the same mechanism. This mechanism assumes four species (two containing four subunits and two containing two subunits) each of which can exist in a protonated and unprotonated form. Inactivation or reactivation induced by changes in pH or temperature reflect the kinetic establishment of a new steady state between these forms. How the apparent pK values which control the distribution of the enzyme between protonated and unprotonated forms describe the pH-dependent characteristics of the enzyme is discussed in terms of the proposed mechanism.", "contents": "Phosphofructokinase. I. Mechanism of the pH-dependent inactivation and reactivation of the rabbit muscle enzyme. The kinetics of inactivation and reactivation of rabbit skeletal muscle phosphofructokinase have been studied as a function of pH and enzyme concentration at constant temperature in phosphate buffer. From the enzyme concentration dependence, we conclude that the minimal mechanism for inactivation involves a protonation step followed by isomerization to an inactive form and then dissociation to a species of one-half the molecular weight. Other data indicate a subsequent isomerization of the dissociated form. The pH and temperature dependence of the inactivation process shows that it is controlled by ionizable groups, and that the apparent pK for these groups is temperature-dependent in such a way as to make the enzyme show the characteristic of cold lability below pH 7. Reactivation of the inactive enzyme occurs by a kinetically different pathway involving deprotonation of an inactive, dissociated form to a form which may either isomerize to another inactive form, or dimerize to the active enzyme. A general mechanism is postulated in which the inactivation and reactivation processes are different aspects of the same mechanism. This mechanism assumes four species (two containing four subunits and two containing two subunits) each of which can exist in a protonated and unprotonated form. Inactivation or reactivation induced by changes in pH or temperature reflect the kinetic establishment of a new steady state between these forms. How the apparent pK values which control the distribution of the enzyme between protonated and unprotonated forms describe the pH-dependent characteristics of the enzyme is discussed in terms of the proposed mechanism."}
{"id": "PMID:9394", "title": "Phosphofructokinase. II. Role of ligands in pH-dependent structural changes of the rabbit muscle enzyme.", "content": "The effect of ligands, including substrates and allosteric effectors, on the pH-dependent inactivation and reactivation of rabbit muscle phosphofructokinase has been examined in terms of the mechanism proposed previously (Bock, P.E. and Fireden, C. (1976) J. Biol. Chem. 251, 5630-5636). It is concluded thatt many ligands exert their effect by binding preferentially to either protonated or unprotonated forms of the enzyme and thus shifting an apparent pK for the inactivation or reactivation process. ATP and fructose 6-phosphate influence the apparent pK to different extents and in different directions, with ATP binding preferentially to the protonated forms and fructose 6-phosphate to the unprotonated forms. Enzyme inactivated by ATP can be reactivated by the addition of fructose 6-phosphate. The experiments indicate that inactivation and reactivation in the presence of these ligands can occur by kinetically different pathways as has been found for these processes in the absence of ligands. The results are discussed in relation to what might be expected for ligand binding properties of the enzyme as a function of pH, temperature, and enzyme concentration. The effect of ATP and MgATP is complex, perhaps representing more than one site of binding. Citrate appears to bind preferentially to protonated forms of the enzyme while fructose 1,6-bisphosphate and AMP bind preferentially to the unprotonated forms. ADP, K+, and NH4+ appear to have little or no preference in binding to different enzyme forms.", "contents": "Phosphofructokinase. II. Role of ligands in pH-dependent structural changes of the rabbit muscle enzyme. The effect of ligands, including substrates and allosteric effectors, on the pH-dependent inactivation and reactivation of rabbit muscle phosphofructokinase has been examined in terms of the mechanism proposed previously (Bock, P.E. and Fireden, C. (1976) J. Biol. Chem. 251, 5630-5636). It is concluded thatt many ligands exert their effect by binding preferentially to either protonated or unprotonated forms of the enzyme and thus shifting an apparent pK for the inactivation or reactivation process. ATP and fructose 6-phosphate influence the apparent pK to different extents and in different directions, with ATP binding preferentially to the protonated forms and fructose 6-phosphate to the unprotonated forms. Enzyme inactivated by ATP can be reactivated by the addition of fructose 6-phosphate. The experiments indicate that inactivation and reactivation in the presence of these ligands can occur by kinetically different pathways as has been found for these processes in the absence of ligands. The results are discussed in relation to what might be expected for ligand binding properties of the enzyme as a function of pH, temperature, and enzyme concentration. The effect of ATP and MgATP is complex, perhaps representing more than one site of binding. Citrate appears to bind preferentially to protonated forms of the enzyme while fructose 1,6-bisphosphate and AMP bind preferentially to the unprotonated forms. ADP, K+, and NH4+ appear to have little or no preference in binding to different enzyme forms."}
{"id": "PMID:9395", "title": "Phosphofructokinase. III. Correlation of the regulatory kinetic and molecular properties of the rabbit muscle enzyme.", "content": "It is shown that the degree of regulatory kinetic behavior of rabbit muscle phosphofructokinase increases at a given pH and lower temperatures, as well as at a given temperature and lower pH values. It is also shown that the regulatory kinetic behavior which appears at lower pH values is inherent in the tetrameric (active) form of the enzyme. We conclude that a portion of the mechanism proposed previously (Bock, P.E., and Frieden, C. (1976) J. Biol. Chem. 251, 5630-5636) to describe the pH and temperature-dependent inactivation or reactivation may also be used to explain the pH and temperature-dependent regulatory kinetic behavior. According to this proposal, two rapidly equilibrating forms of the enzyme, which differ in the degree of protonation of specific residues, differ in their ability to bind substrates. While the protonated form of the enzyme subsequently becomes inactive by isomerization and dissociation, this process is too slow to affect the kinetic results, making direct comparisons between the association-dissociation behavior and regulatory kinetic behavior invalid. The time dependence of the processes of inactivation or reactivation in the presence or absence of ligands and of the appearance of regulatory kinetic behavior is discussed in relation to their possible role in metabolic regulation.", "contents": "Phosphofructokinase. III. Correlation of the regulatory kinetic and molecular properties of the rabbit muscle enzyme. It is shown that the degree of regulatory kinetic behavior of rabbit muscle phosphofructokinase increases at a given pH and lower temperatures, as well as at a given temperature and lower pH values. It is also shown that the regulatory kinetic behavior which appears at lower pH values is inherent in the tetrameric (active) form of the enzyme. We conclude that a portion of the mechanism proposed previously (Bock, P.E., and Frieden, C. (1976) J. Biol. Chem. 251, 5630-5636) to describe the pH and temperature-dependent inactivation or reactivation may also be used to explain the pH and temperature-dependent regulatory kinetic behavior. According to this proposal, two rapidly equilibrating forms of the enzyme, which differ in the degree of protonation of specific residues, differ in their ability to bind substrates. While the protonated form of the enzyme subsequently becomes inactive by isomerization and dissociation, this process is too slow to affect the kinetic results, making direct comparisons between the association-dissociation behavior and regulatory kinetic behavior invalid. The time dependence of the processes of inactivation or reactivation in the presence or absence of ligands and of the appearance of regulatory kinetic behavior is discussed in relation to their possible role in metabolic regulation."}
{"id": "PMID:9396", "title": "Re-evaluation of the H+/site ratio of mitochondrial electron transport with the oxygen pulse technique.", "content": "The number of protons ejected per pair of electrons passing each energy-conserving site in the electron transport chain (the H+/site ratio) has been investigated in rat liver mitochondria by means of the oxygen pulse technique introduced by Mitchell and Moyle (1967) (Biochem. J. 105, 1147-1162). The usual H+/site values of 2.0 observed by this method were found to be substantially underestimated as a result of the influx of phosphate into the mitochondria. This was shown by three different kinds of experiments. 1. Addition of N-ethylmaleimide or mersalyl, inhibitors of mitochondrial phosphate transport, increased the H+/site ratio from 2.0 to 3.0. The dependence of this effect on the concentration of either inhibitor was identical with that for inhibition of phosphate transport. Added phosphate diminished the H+/site ratio to values below 2.0 in the absence of N-ethylmaleimide. N-Ethylmaleimide protected the elevated H+/site ratio of 3.0 against the deleterious effect of added phosphate, but did not prevent a lowering effect of weak acid anions such as 3-hydroxybutyrate. 2. Prior washing of mitochondria to remove the endogenous phosphate that leaks out during the anaerobic preincubation led to H+/site ratios near 3.0, which were not increased by N-ethylmaleimide. Addition of low concentrations of phosphate to such phosphate-depleted mitochondria decreased the H+/site ratio to 2.0; addition of N-ethylmaleimide returned the ratio to 3.0. 3. Lowering the temperature to 5 degrees, which slows down phosphate transport, led to H+/site values of 3.0 even in the absence of N-ethylmaleimide. The H+/site ratio of 3.0 observed in the absence of phosphate movements was not dependent on any narrowly limited set of experimental conditions. It occurred with either Ca2+ or K+ (in the presence of valinomycin) as mobile permeant cation. It was independent of the concentration of succinate, oxygen, mitochondria, or rotenone, additions of Ca2+, Li+, or Na+ and was independent of medium pH between 6.5 and 7.5. Inhibitors of the transport of ions or acids other than phosphate did not affect the H+/site ratio. These results indicate that re-uptake of endogenous phosphate, lost from mitochondria during anaerobic preincubation, reduces the observed H+ ejection and leads to underestimated H+/site ratios of 2.0 in the oxygen pulse method. When phosphate movements are eliminated by the procedures described above, the observed H+/site ratio is about 3.0. This value appears to be closer to the true H+/site ratio for the primary H+ ejection process during electron transport.", "contents": "Re-evaluation of the H+/site ratio of mitochondrial electron transport with the oxygen pulse technique. The number of protons ejected per pair of electrons passing each energy-conserving site in the electron transport chain (the H+/site ratio) has been investigated in rat liver mitochondria by means of the oxygen pulse technique introduced by Mitchell and Moyle (1967) (Biochem. J. 105, 1147-1162). The usual H+/site values of 2.0 observed by this method were found to be substantially underestimated as a result of the influx of phosphate into the mitochondria. This was shown by three different kinds of experiments. 1. Addition of N-ethylmaleimide or mersalyl, inhibitors of mitochondrial phosphate transport, increased the H+/site ratio from 2.0 to 3.0. The dependence of this effect on the concentration of either inhibitor was identical with that for inhibition of phosphate transport. Added phosphate diminished the H+/site ratio to values below 2.0 in the absence of N-ethylmaleimide. N-Ethylmaleimide protected the elevated H+/site ratio of 3.0 against the deleterious effect of added phosphate, but did not prevent a lowering effect of weak acid anions such as 3-hydroxybutyrate. 2. Prior washing of mitochondria to remove the endogenous phosphate that leaks out during the anaerobic preincubation led to H+/site ratios near 3.0, which were not increased by N-ethylmaleimide. Addition of low concentrations of phosphate to such phosphate-depleted mitochondria decreased the H+/site ratio to 2.0; addition of N-ethylmaleimide returned the ratio to 3.0. 3. Lowering the temperature to 5 degrees, which slows down phosphate transport, led to H+/site values of 3.0 even in the absence of N-ethylmaleimide. The H+/site ratio of 3.0 observed in the absence of phosphate movements was not dependent on any narrowly limited set of experimental conditions. It occurred with either Ca2+ or K+ (in the presence of valinomycin) as mobile permeant cation. It was independent of the concentration of succinate, oxygen, mitochondria, or rotenone, additions of Ca2+, Li+, or Na+ and was independent of medium pH between 6.5 and 7.5. Inhibitors of the transport of ions or acids other than phosphate did not affect the H+/site ratio. These results indicate that re-uptake of endogenous phosphate, lost from mitochondria during anaerobic preincubation, reduces the observed H+ ejection and leads to underestimated H+/site ratios of 2.0 in the oxygen pulse method. When phosphate movements are eliminated by the procedures described above, the observed H+/site ratio is about 3.0. This value appears to be closer to the true H+/site ratio for the primary H+ ejection process during electron transport."}
{"id": "PMID:9397", "title": "Facile alkylation of methionine by benzyl bromide and demonstration of fumarase inactivation accompanied by alkylation of a methionine residue.", "content": "Benzyl bromide is a selective alkylator of sulfur nucleophiles including methionine and cysteine. Only the mercaptide ion is a more efficient nucleophile than is the sulfur ether of methionine. Alkylation rates relative to methionine are 200: less than or equal to 0.03: less than or equal to 0.03: less than or equal to 0.02 for GS-, histidine, tryptophan, and GSH, respectively. Alkylation of methionine by benzyl bromide is more than 50 times faster than alkylation by iodoacetate. Fumarase is readily inactivated by exposure to benzyl bromide at pH 6.6 to 6.8 accompanied by alkylation of close to 1 methionine residue/subunit. Fumarase fully inactivated by exposure to benzyl bromide shows no detected alkylation of amino acid residues other than methionine. The rate of inactivation of fumarase by benzyl bromide is decreased about 4-fold by the presence of excess substrates. Denaturation of fumarase in 6 M urea at pH 6.5 exposes additional methionine as well as cysteine residues to alkylation.", "contents": "Facile alkylation of methionine by benzyl bromide and demonstration of fumarase inactivation accompanied by alkylation of a methionine residue. Benzyl bromide is a selective alkylator of sulfur nucleophiles including methionine and cysteine. Only the mercaptide ion is a more efficient nucleophile than is the sulfur ether of methionine. Alkylation rates relative to methionine are 200: less than or equal to 0.03: less than or equal to 0.03: less than or equal to 0.02 for GS-, histidine, tryptophan, and GSH, respectively. Alkylation of methionine by benzyl bromide is more than 50 times faster than alkylation by iodoacetate. Fumarase is readily inactivated by exposure to benzyl bromide at pH 6.6 to 6.8 accompanied by alkylation of close to 1 methionine residue/subunit. Fumarase fully inactivated by exposure to benzyl bromide shows no detected alkylation of amino acid residues other than methionine. The rate of inactivation of fumarase by benzyl bromide is decreased about 4-fold by the presence of excess substrates. Denaturation of fumarase in 6 M urea at pH 6.5 exposes additional methionine as well as cysteine residues to alkylation."}
{"id": "PMID:9398", "title": "Triacylglycerol synthesis in isolated fat cells. Evidence that the sn-glycerol-3-phosphate and dihydroxyacetone phosphate acyltransferase activities are dual catalytic functions of a single microsomal enzyme.", "content": "The acyl-CoA:sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) (glycerol-P acyltransferase) and acyl-CoA:dihydroxyacetone phosphate acyltransferase (EC 2.3.1.42) (DHAP acyltransferase) activities were investigated in vitro in order to evaluate the quantitative contribution of the glycerol-P and DHAP pathways for the synthesis of triacylglycerols in isolated fat cells and to test the hypothesis that these two activities may be dual catalytic functions of a single enzyme. More than 85% of both acyltransferase activities was associated with the microsomal subcellular fraction. The microsomal glycerol-P acyltransferase activity showed an apparent Km of 8 muM for glycerol-P with a Vmax of 15.6 nmol/min/mg, while the DHAP acyltransferase activity showed an apparent Km of 40 muM for DHAP with a Vmax of 9.7 nmol/min/mg. Glycerol-P was a competitive inhibitor (Ki = 7.2 muM) of the DHAP acyltransferase, and DHAP was a competitive inhibitor (Ki = 92 muM) of the glycerol-P acyltransferase. The two acyltransferase activities showed virtual identity in their pH dependence, acyl-CoA chain length dependence, thermolability, and inactivation by N-ethylmaleimide. Trypsin, detergents, collagenase, phospholipases, and various salts and organic solvents also had similar effects on both activities. Taken as a whole, the data strongly suggest that the microsomal glycerol-P and DHAP acyltransferase activities actually represent dual functions of a single enzyme. Calculations based on the above kinetic constants and previously reported glycerol-P and DHAP pools in adipocytes suggest that the in vivo ratio of glycerol-P to DHAP acylation should be greater than 24:1.", "contents": "Triacylglycerol synthesis in isolated fat cells. Evidence that the sn-glycerol-3-phosphate and dihydroxyacetone phosphate acyltransferase activities are dual catalytic functions of a single microsomal enzyme. The acyl-CoA:sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15) (glycerol-P acyltransferase) and acyl-CoA:dihydroxyacetone phosphate acyltransferase (EC 2.3.1.42) (DHAP acyltransferase) activities were investigated in vitro in order to evaluate the quantitative contribution of the glycerol-P and DHAP pathways for the synthesis of triacylglycerols in isolated fat cells and to test the hypothesis that these two activities may be dual catalytic functions of a single enzyme. More than 85% of both acyltransferase activities was associated with the microsomal subcellular fraction. The microsomal glycerol-P acyltransferase activity showed an apparent Km of 8 muM for glycerol-P with a Vmax of 15.6 nmol/min/mg, while the DHAP acyltransferase activity showed an apparent Km of 40 muM for DHAP with a Vmax of 9.7 nmol/min/mg. Glycerol-P was a competitive inhibitor (Ki = 7.2 muM) of the DHAP acyltransferase, and DHAP was a competitive inhibitor (Ki = 92 muM) of the glycerol-P acyltransferase. The two acyltransferase activities showed virtual identity in their pH dependence, acyl-CoA chain length dependence, thermolability, and inactivation by N-ethylmaleimide. Trypsin, detergents, collagenase, phospholipases, and various salts and organic solvents also had similar effects on both activities. Taken as a whole, the data strongly suggest that the microsomal glycerol-P and DHAP acyltransferase activities actually represent dual functions of a single enzyme. Calculations based on the above kinetic constants and previously reported glycerol-P and DHAP pools in adipocytes suggest that the in vivo ratio of glycerol-P to DHAP acylation should be greater than 24:1."}
{"id": "PMID:9399", "title": "Properties of a human liver ribonuclease. Inhibition by polynucleotides and specificity for phosphodiester bond cleavage to yield purine nucleosides at the 5' termini.", "content": "A ribonuclease, purified 2500-fold from human liver, was found to be inactive against synthetic homopolynucleotides, whereas synthetic co-polymers containing adenylic acid were rapidly degraded. The specificity of the RNase is unique in that only purine residues, in a 5:4 ratio of guanylic to adenylic acid, are found at the 5' termini of the degradation products of yeast RNA. No specificity was observed at the 3' termini of the fragments. When analyzed by DEAE-cellulose chromatography, approximately 80% of the oligonucletoides were 4 to 11 residues in length. The hydrolysis of RNA by the liver enzyme, when examined in low ionic strength buffer, could be increased severalfold over control levels by the addition of polyamines. The enzyme was found to exist as two distinct species on sucrose gradients, with molecular weights of 128,000 and 14,000. However, the addition of spermidine to the gradients resulted in the recovery of all the enzyme activity as the smaller species. The polyamines were also shown to reverse the inhibition of the enzyme by the ordered polynucleotides, polyguanylic acid and polyadenylic acid. Inhibition of enzyme activity by the polyadenylic acid segment of various mammalian mRNAs was also demonstrated.", "contents": "Properties of a human liver ribonuclease. Inhibition by polynucleotides and specificity for phosphodiester bond cleavage to yield purine nucleosides at the 5' termini. A ribonuclease, purified 2500-fold from human liver, was found to be inactive against synthetic homopolynucleotides, whereas synthetic co-polymers containing adenylic acid were rapidly degraded. The specificity of the RNase is unique in that only purine residues, in a 5:4 ratio of guanylic to adenylic acid, are found at the 5' termini of the degradation products of yeast RNA. No specificity was observed at the 3' termini of the fragments. When analyzed by DEAE-cellulose chromatography, approximately 80% of the oligonucletoides were 4 to 11 residues in length. The hydrolysis of RNA by the liver enzyme, when examined in low ionic strength buffer, could be increased severalfold over control levels by the addition of polyamines. The enzyme was found to exist as two distinct species on sucrose gradients, with molecular weights of 128,000 and 14,000. However, the addition of spermidine to the gradients resulted in the recovery of all the enzyme activity as the smaller species. The polyamines were also shown to reverse the inhibition of the enzyme by the ordered polynucleotides, polyguanylic acid and polyadenylic acid. Inhibition of enzyme activity by the polyadenylic acid segment of various mammalian mRNAs was also demonstrated."}
{"id": "PMID:9400", "title": "Accumulation of neutral lipids in Saccharomyces carlsbergensis by myo-inositol deficiency and its mechanism. Reciprocal regulation of yeast acetyl-CoA carboxylase by fructose bisphosphate and citrate.", "content": "The abnormal accumulation of lipids due to myo-inositol deficiency in Saccharomyces carlsbergensis, and the mechanism involved was investigated. The deficient cells contained much more neutral lipids with a greater ratio of unsaturated fatty acids compared to the supplemented cells, whereas there was no significant change in their phospholipid contents. The biosynthesis of fatty acids and sterols from acetate, and of triacylglycerols and sterol esters from palmitate was markedly augmented in the deficient cells. Acetyl-CoA carboxylase activity of the deficient supernatant was 2- to 5-fold higher than that of the supplemented. However, the activity from both sources was not significantly different after Sephadex G-25 gel filtration of the supernatant, suggesting the presence of low molecular effector(s) in the deficient supernatant. There was a great increase in acid-soluble glycogen, trehalose, and fructose-1,6-P2, as well as a drastic decrease in citrate in the deficient cells. Their intracellular levels were calculated so that their effects on acetyl-CoA carboxylase was examined over the range of physiological concentration. Citrate strongly inhibited the enzyme activity of the supernatant, but it had no effect on the preparation after gel filtration. On the other hand, fructose-1,6-P2 stimulated the enzyme activity both before and after gel filtration. The acetyl-CoA carboxylase activity in the gel filtrate was measured as a function of citrate concentration at several fixed concentrations of fructose-1,6-P2. Citrate counteracted the activation by fructose-1,6-P2 in a dose-dependent manner. Citrate lacked the inhibitory effect in the absence of fructose-1,6-P2. It was concluded from these results that neutral lipid accumulation in the deficient cells reflected an increase in the synthesis of fatty acids, at least partly based on an enhancement of acetyl-CoA carboxylase activity, and that the operation of a reciprocal regulation of the enzyme by fructose-1,6-P2 and citrate caused a marked elevation of the enzyme activity in the deficient cells with a high fructose-1,6-P2 level and a low citrate level.", "contents": "Accumulation of neutral lipids in Saccharomyces carlsbergensis by myo-inositol deficiency and its mechanism. Reciprocal regulation of yeast acetyl-CoA carboxylase by fructose bisphosphate and citrate. The abnormal accumulation of lipids due to myo-inositol deficiency in Saccharomyces carlsbergensis, and the mechanism involved was investigated. The deficient cells contained much more neutral lipids with a greater ratio of unsaturated fatty acids compared to the supplemented cells, whereas there was no significant change in their phospholipid contents. The biosynthesis of fatty acids and sterols from acetate, and of triacylglycerols and sterol esters from palmitate was markedly augmented in the deficient cells. Acetyl-CoA carboxylase activity of the deficient supernatant was 2- to 5-fold higher than that of the supplemented. However, the activity from both sources was not significantly different after Sephadex G-25 gel filtration of the supernatant, suggesting the presence of low molecular effector(s) in the deficient supernatant. There was a great increase in acid-soluble glycogen, trehalose, and fructose-1,6-P2, as well as a drastic decrease in citrate in the deficient cells. Their intracellular levels were calculated so that their effects on acetyl-CoA carboxylase was examined over the range of physiological concentration. Citrate strongly inhibited the enzyme activity of the supernatant, but it had no effect on the preparation after gel filtration. On the other hand, fructose-1,6-P2 stimulated the enzyme activity both before and after gel filtration. The acetyl-CoA carboxylase activity in the gel filtrate was measured as a function of citrate concentration at several fixed concentrations of fructose-1,6-P2. Citrate counteracted the activation by fructose-1,6-P2 in a dose-dependent manner. Citrate lacked the inhibitory effect in the absence of fructose-1,6-P2. It was concluded from these results that neutral lipid accumulation in the deficient cells reflected an increase in the synthesis of fatty acids, at least partly based on an enhancement of acetyl-CoA carboxylase activity, and that the operation of a reciprocal regulation of the enzyme by fructose-1,6-P2 and citrate caused a marked elevation of the enzyme activity in the deficient cells with a high fructose-1,6-P2 level and a low citrate level."}
{"id": "PMID:9401", "title": "Collagen cross-linking. Purification and substrate specificity of lysyl oxidase.", "content": "Lysyl oxidase is a specific amine oxidase that catalyzes the formation of aldehyde cross-link intermediates in collagen and elastin. In this study, lysyl oxidase from embryonic chick cartilage was purified to constant specific activity and a single protein band on sodium dodecyl sulfate acrylamide gel electrophoresis. This band had an apparent molecular weight of 62,000. The eluted protein cross-reacted with inhibiting antisera developed against highly purified lysyl oxidase. The highly purified enzyme was active with both insoluble elastin and embryonic chick skin or bone collagen precipitated as reconstituted, native fibrils. There was low activity with nonhydroxylated collagen, collagen monomers, or native fibrils isolated from lathyritic calvaria. The maximum number of aldehyde intermediates formed per molecule of collagen that became insoluble was two. These results indicate that lysyl oxidase has maximum activity on ordered aggregates of collagen molecules that may be overlapping associations of only a few collagen molecules across. Formation of aldehyde intermediates and cross-links during fibril formation may facilitate the biosynthesis of stable collagen fibrils and contribute to increased fibril tensile strength in vivo.", "contents": "Collagen cross-linking. Purification and substrate specificity of lysyl oxidase. Lysyl oxidase is a specific amine oxidase that catalyzes the formation of aldehyde cross-link intermediates in collagen and elastin. In this study, lysyl oxidase from embryonic chick cartilage was purified to constant specific activity and a single protein band on sodium dodecyl sulfate acrylamide gel electrophoresis. This band had an apparent molecular weight of 62,000. The eluted protein cross-reacted with inhibiting antisera developed against highly purified lysyl oxidase. The highly purified enzyme was active with both insoluble elastin and embryonic chick skin or bone collagen precipitated as reconstituted, native fibrils. There was low activity with nonhydroxylated collagen, collagen monomers, or native fibrils isolated from lathyritic calvaria. The maximum number of aldehyde intermediates formed per molecule of collagen that became insoluble was two. These results indicate that lysyl oxidase has maximum activity on ordered aggregates of collagen molecules that may be overlapping associations of only a few collagen molecules across. Formation of aldehyde intermediates and cross-links during fibril formation may facilitate the biosynthesis of stable collagen fibrils and contribute to increased fibril tensile strength in vivo."}
{"id": "PMID:9402", "title": "Collagen cross-linking. Synthesis of collagen cross-links in vitro with highly purified lysyl oxidase.", "content": "In this paper, the synthesis of collagen cross-links in vitro was investigated in a defined system consisting of highly purified chick cartilage lysyl oxidase and chick bone collagen fibrils. Cross-link synthesis in vitro was quite similar to the biosynthesis of collagen cross-links in vivo. Enzyme-dependent synthesis of cross-link intermediates and cross-linked collagen derived from lathyritic collagen occurred. The concentration of the two principal reducible cross-links, N6:6'-dehydro-5,5'-dihydroxylysinonorleucine and N6:6'-dehydro-5-hydroxylysinonorleucine, increased to a peak value of approximately two cross-links per molecule and then decreased. Synthesis of histidinohydroxymerodesmosine and a second polyfunctional cross-link of unknown structure began after synthesis of bifunctional cross-links was largely completed and proceeded linearly afterwards. Inhibition of lysyl oxidase after the bulk of bifunctional cross-link synthesis had occurred did not alter the rate of decrease in reducible cross-link concentration but did inhibit further histidinohydroxymerodesmosine synthesis. These results indicate that lysyl oxidase and collagen fibrils are the only macromolecules required for cross-link biosynthesis in vivo. It is likely that the decrease in reducible cross-links observed during fibril maturation results from spontaneous reactions within the collagen fibril rather than additional enzymatic reactions.", "contents": "Collagen cross-linking. Synthesis of collagen cross-links in vitro with highly purified lysyl oxidase. In this paper, the synthesis of collagen cross-links in vitro was investigated in a defined system consisting of highly purified chick cartilage lysyl oxidase and chick bone collagen fibrils. Cross-link synthesis in vitro was quite similar to the biosynthesis of collagen cross-links in vivo. Enzyme-dependent synthesis of cross-link intermediates and cross-linked collagen derived from lathyritic collagen occurred. The concentration of the two principal reducible cross-links, N6:6'-dehydro-5,5'-dihydroxylysinonorleucine and N6:6'-dehydro-5-hydroxylysinonorleucine, increased to a peak value of approximately two cross-links per molecule and then decreased. Synthesis of histidinohydroxymerodesmosine and a second polyfunctional cross-link of unknown structure began after synthesis of bifunctional cross-links was largely completed and proceeded linearly afterwards. Inhibition of lysyl oxidase after the bulk of bifunctional cross-link synthesis had occurred did not alter the rate of decrease in reducible cross-link concentration but did inhibit further histidinohydroxymerodesmosine synthesis. These results indicate that lysyl oxidase and collagen fibrils are the only macromolecules required for cross-link biosynthesis in vivo. It is likely that the decrease in reducible cross-links observed during fibril maturation results from spontaneous reactions within the collagen fibril rather than additional enzymatic reactions."}
{"id": "PMID:9403", "title": "Stimulation of guanylate cyclase of fibroblasts by free fatty acids.", "content": "The membranous guanylate cyclase of Balb 3T3 fibroblasts was stimulated by a fraction of calf serum extracted by ether. Stimulation was observed with Mg2+ as the only bivalent cation in the presence of Lubrol PX. The activator co-chromatographed with free fatty acids, and several of these were found to stimulate guanylate cyclase. Among the saturated fatty acids, myristic acid had the highest activity. Stimulating activity diminished as the hydrocarbon chain of the fatty acid was lengthened or shortened. Introduction of an unsaturated bond enhanced the activation by the longer fatty acids. This pattern of specificity is similar to that observed for the effect of fatty acids on many other membranous functions. Under appropriate conditions fatty acids were found to stimulate guanylate cyclase activity in the absence of Lubrol PX. The relationship among the effects of Mg2+, Mn2+, Lubrol PX, and fatty acids on enzyme activity was examined. On the basis of these studies, it appears that fatty acids stimulate the enzyme by a mechanism different from nonionic detergents or Mn2+.", "contents": "Stimulation of guanylate cyclase of fibroblasts by free fatty acids. The membranous guanylate cyclase of Balb 3T3 fibroblasts was stimulated by a fraction of calf serum extracted by ether. Stimulation was observed with Mg2+ as the only bivalent cation in the presence of Lubrol PX. The activator co-chromatographed with free fatty acids, and several of these were found to stimulate guanylate cyclase. Among the saturated fatty acids, myristic acid had the highest activity. Stimulating activity diminished as the hydrocarbon chain of the fatty acid was lengthened or shortened. Introduction of an unsaturated bond enhanced the activation by the longer fatty acids. This pattern of specificity is similar to that observed for the effect of fatty acids on many other membranous functions. Under appropriate conditions fatty acids were found to stimulate guanylate cyclase activity in the absence of Lubrol PX. The relationship among the effects of Mg2+, Mn2+, Lubrol PX, and fatty acids on enzyme activity was examined. On the basis of these studies, it appears that fatty acids stimulate the enzyme by a mechanism different from nonionic detergents or Mn2+."}
{"id": "PMID:9404", "title": "Identification of a functional arginine residue involved in coenzyme binding by the NADP-specific glutamate dehydrogenase of Neurospora.", "content": "The NADP-specific glutamate dehydrogenase (EC 1.4.1.4) of Neurospora crassa is inhibited by reaction with 1,2-cyclohexanedione which binds to arginine residues. With the 14C-labeled reagent, a peptide was isolated with the sequence: Gly-Gly-Leu-Arg-Leu-His-Pro-Ser-Val-Asn-Leu, corresponding to residues 78 through 88 in the protein. The arginine, residue 81, was present as N7,N8-(1,2-dihydroxycyclohex-1,2-ylene)-arginyl (or DHCH-arginine). Present evidence indicates that this arginine residue resides at or near the nicotinamide binding domain of the enzyme. Similar sequences are present in the bovine liver enzyme (EC 1.4.1.3) and the NAD-specific glutamate dehydrogenase of Neurospora (EC 1.4.1.2).", "contents": "Identification of a functional arginine residue involved in coenzyme binding by the NADP-specific glutamate dehydrogenase of Neurospora. The NADP-specific glutamate dehydrogenase (EC 1.4.1.4) of Neurospora crassa is inhibited by reaction with 1,2-cyclohexanedione which binds to arginine residues. With the 14C-labeled reagent, a peptide was isolated with the sequence: Gly-Gly-Leu-Arg-Leu-His-Pro-Ser-Val-Asn-Leu, corresponding to residues 78 through 88 in the protein. The arginine, residue 81, was present as N7,N8-(1,2-dihydroxycyclohex-1,2-ylene)-arginyl (or DHCH-arginine). Present evidence indicates that this arginine residue resides at or near the nicotinamide binding domain of the enzyme. Similar sequences are present in the bovine liver enzyme (EC 1.4.1.3) and the NAD-specific glutamate dehydrogenase of Neurospora (EC 1.4.1.2)."}
{"id": "PMID:9405", "title": "X-ray and functional studies of hemoglobins Nancy and Cochin-Port-Royal.", "content": "The mutations in hemoglobin Nancy beta145(HC2) Tyr leads to Asp and hemoglobin Cochin-Portal-Royal beta146(HC3) His leads to Arg involve residues which are thought to be essential for the full expression of allosteric action in hemoglobin. Relative to the structure of deoxyhemoglobin A, our x-ray study of deoxyhemoglobin Nancy shows severe disordering of the beta chain COOH-terminal tetrapeptide and a possible movement of the beta heme iron atom toward the plane of the porphyrin ring. These structural perturbations result in a high oxygen affinity, reduced Bohr effect, and lack of cooperatively in hemoglobin Nancy. In the presence of inositol hexaphosphate (IHP), the Hill constant for hemoglobin Nancy increases from 1.1 to 2.0. But relative to its action on hemoglobin A, IHP is much less effective in reducing the oxygen affinity and in increasing the Bohr effect of hemoglobin Nancy. This indicates that IHP does not influence the R in equilibrium T equilibrium as much in hemoglobin Nancy as in hemoglobin A, and this probably is due to the disordering of His 143beta which is known to be part of the IHP binding site. IHP is also known to produce large changes in the absorption spectrum of methemoglobin A, but we find that it has no effect on the spectrum of methemoglobin Nancy. In contrast to the large structural changes in deoxyhemoglobin Nancy, the structure of deoxyhemoglobin Cochin-Port-Royal differs from deoxyhemoglobin A only in the position of the side chain of residue 146beta. The intrasubunit salt bridge between His 146beta and Asp 94beta in deoxyhemoglobin A is lost in deoxyhemoglobin Cochin-Portal-Royal with the guanidinium ion of Arg 146beta floating freely in solution. This small difference in structure results in a reduced Bohr effect, but does not cause a change in the Hill coefficient, the response to 2,3-diphosphoglycerate, or the oxygen affinity at physiological pH.", "contents": "X-ray and functional studies of hemoglobins Nancy and Cochin-Port-Royal. The mutations in hemoglobin Nancy beta145(HC2) Tyr leads to Asp and hemoglobin Cochin-Portal-Royal beta146(HC3) His leads to Arg involve residues which are thought to be essential for the full expression of allosteric action in hemoglobin. Relative to the structure of deoxyhemoglobin A, our x-ray study of deoxyhemoglobin Nancy shows severe disordering of the beta chain COOH-terminal tetrapeptide and a possible movement of the beta heme iron atom toward the plane of the porphyrin ring. These structural perturbations result in a high oxygen affinity, reduced Bohr effect, and lack of cooperatively in hemoglobin Nancy. In the presence of inositol hexaphosphate (IHP), the Hill constant for hemoglobin Nancy increases from 1.1 to 2.0. But relative to its action on hemoglobin A, IHP is much less effective in reducing the oxygen affinity and in increasing the Bohr effect of hemoglobin Nancy. This indicates that IHP does not influence the R in equilibrium T equilibrium as much in hemoglobin Nancy as in hemoglobin A, and this probably is due to the disordering of His 143beta which is known to be part of the IHP binding site. IHP is also known to produce large changes in the absorption spectrum of methemoglobin A, but we find that it has no effect on the spectrum of methemoglobin Nancy. In contrast to the large structural changes in deoxyhemoglobin Nancy, the structure of deoxyhemoglobin Cochin-Port-Royal differs from deoxyhemoglobin A only in the position of the side chain of residue 146beta. The intrasubunit salt bridge between His 146beta and Asp 94beta in deoxyhemoglobin A is lost in deoxyhemoglobin Cochin-Portal-Royal with the guanidinium ion of Arg 146beta floating freely in solution. This small difference in structure results in a reduced Bohr effect, but does not cause a change in the Hill coefficient, the response to 2,3-diphosphoglycerate, or the oxygen affinity at physiological pH."}
{"id": "PMID:9406", "title": "A stereochemical method for detection of ATP terminal phosphate transfer in enzymatic reactions. Glutamine synthetase.", "content": "An isotope scrambling method is described for the detection of transient [Enz:ADP:P-X] formation from [18O]ATP in ATP-coupled enzyme reactions. The method makes use of torsional symmetry of the newly formed (see article) group in ADP. [18 O]ATP labeled in the betagama bridge oxygen was incubated with enzyme and reversible cleavage of the PbetaO -- Pgamma bond was detected by the appearance of 18O in the beta nonbridge oxygens of the ATP pool. Experiments with sheep brain and Escherichia coli glutamine synthetases show that cleavage of ATP of enzyme-bound ADP and P-X requires glutamate. The exchange catalyzed by the E. coli enzyme with glutamate occurs in the absence of ammonia and is partially inhibited by added NH4Cl, as expected if the exchange is in the mechanistic pathway for glutamine synthesis. The results provide kinetic support for a two-step mechanism where phosphoryl transfer from ATP to glutamate precedes reaction with ammonia.", "contents": "A stereochemical method for detection of ATP terminal phosphate transfer in enzymatic reactions. Glutamine synthetase. An isotope scrambling method is described for the detection of transient [Enz:ADP:P-X] formation from [18O]ATP in ATP-coupled enzyme reactions. The method makes use of torsional symmetry of the newly formed (see article) group in ADP. [18 O]ATP labeled in the betagama bridge oxygen was incubated with enzyme and reversible cleavage of the PbetaO -- Pgamma bond was detected by the appearance of 18O in the beta nonbridge oxygens of the ATP pool. Experiments with sheep brain and Escherichia coli glutamine synthetases show that cleavage of ATP of enzyme-bound ADP and P-X requires glutamate. The exchange catalyzed by the E. coli enzyme with glutamate occurs in the absence of ammonia and is partially inhibited by added NH4Cl, as expected if the exchange is in the mechanistic pathway for glutamine synthesis. The results provide kinetic support for a two-step mechanism where phosphoryl transfer from ATP to glutamate precedes reaction with ammonia."}
{"id": "PMID:9407", "title": "Steroid 5alpha-reductase in cultured human fibroblasts. Biochemical and genetic evidence for two distinct enzyme activities.", "content": "Various properties of the steroid 5alpha-reductase have been examined in cell-free extracts of skin and of fibroblasts cultured from genital and nongenital skin from control subjects and from patients with several forms of male pseudohermaphroditism. When 20alpha-hydroxy-4-[1,2-3H] pregnen-3-one was used as substrate, two 5alpha-reductase activities could be demonstrated in intact skin and cultured fibroblasts. The major activity, previously described for microsomes from human prepuce and extracts of cultured foreskin fibroblasts, is characterized by a narrow pH optimum near 5.5 and is limited to fibroblasts derived from genital skin. A second activity, not limited by the site of biopsy, has been demonstrated over a higher and broader range of pH (from 7 to 9); this enzyme activity is found in both genital and nongenital skin and in fibroblasts cultured from all skin regions. Whereas there is wide variability in the activity at pH 5.5 in genital skin fibroblasts, the activity at pH 7 to 9 is similar in fibroblasts derived from all anatomical sites. The two activities exhibit different kinetics with respect to steroid substrate and are also dissimilar in their subcellular distributions. Other properties, such as coenzyme requirement, steroid substrate specificity, and instability with increasing temperature, appear to be similar.", "contents": "Steroid 5alpha-reductase in cultured human fibroblasts. Biochemical and genetic evidence for two distinct enzyme activities. Various properties of the steroid 5alpha-reductase have been examined in cell-free extracts of skin and of fibroblasts cultured from genital and nongenital skin from control subjects and from patients with several forms of male pseudohermaphroditism. When 20alpha-hydroxy-4-[1,2-3H] pregnen-3-one was used as substrate, two 5alpha-reductase activities could be demonstrated in intact skin and cultured fibroblasts. The major activity, previously described for microsomes from human prepuce and extracts of cultured foreskin fibroblasts, is characterized by a narrow pH optimum near 5.5 and is limited to fibroblasts derived from genital skin. A second activity, not limited by the site of biopsy, has been demonstrated over a higher and broader range of pH (from 7 to 9); this enzyme activity is found in both genital and nongenital skin and in fibroblasts cultured from all skin regions. Whereas there is wide variability in the activity at pH 5.5 in genital skin fibroblasts, the activity at pH 7 to 9 is similar in fibroblasts derived from all anatomical sites. The two activities exhibit different kinetics with respect to steroid substrate and are also dissimilar in their subcellular distributions. Other properties, such as coenzyme requirement, steroid substrate specificity, and instability with increasing temperature, appear to be similar."}
{"id": "PMID:9408", "title": "The NADH dehydrogenase of the respiratory chain of Escherichia coli. II. Kinetics of the purified enzyme and the effects of antibodies elicited against it on membrane-bound and free enzyme.", "content": "The purified respiratory chain NADH dehydrogenase of Escherichia coli oxidizes NADH with either dichlorophenolindophenol (DCIP). ferricyanide, or menadione as electron acceptors, with values for NADH are similar with the three electron acceptors (approximately 50 muM). The purified enzyme contains no flavin and has an absolute requirement for FAD, with Km values around 4 muM. The pH optimum of the enzyme appears to be between 6.5 and 7; the optimum is difficult to establish because of nonenzymatic reduction of DCIP at the lower pH values. Potassium cyanide stimulates the DCIP reductase activity about 2-fold, but has no effect on ferricyanide reductase. The enzyme exhibits hyperbolic kinetics with respect to NADH concentration in both the ferricyanide and DCIP reductase assays, but cooperatively is seen in the menadione reductase reaction. NAD+ is an effective competitive inhibitor of the reaction (Ki congruent to 20 muM); in the presence of NAD+, the NADH saturation curve becomes cooperative, even in the DCIP reductase assay. Many adenine containing nucleotides are competitive inhibitors of the enzyme. The apparent Ki values for these nucleotides as inhibitors of the purified enzyme, the membrane-bound NADH dehydrogenase, and the NADH oxidase are equivalent. An examination of inhibitory effects of a series of adenine nucleotides suggests that the inhibitors act as analogues of NAD+, which is the true physiological inhibitor. The results suggest that the enzyme in situ is always partially inhibited by the levels of NAD- in the E coli cell, and thus behaves in a cooperative fashion to changes in the NAD+/NADH ratio. An antibody has been elicited against the purified NADH dehydrogenase. Immunodiffusion and crossed immunoelectrophoresis show that the antibody is directed principally against the NADH dehydrogenase, with some activity against minor contaminants in the purified preparation. The antibody inhibits NADH dehydrogenase activity 50% at saturating levels. When this antibody preparation is used to examine solubilized membrane preparations, two major immunoprecipitates are found. A parallel inhibition of the membrane-bound NADH dehydrogenase and NADH oxidase activities is seen, supporting the hypothesis that the purified enzyme is indeed a component of the respiratory chain-dependent NADH oxidase pathway.", "contents": "The NADH dehydrogenase of the respiratory chain of Escherichia coli. II. Kinetics of the purified enzyme and the effects of antibodies elicited against it on membrane-bound and free enzyme. The purified respiratory chain NADH dehydrogenase of Escherichia coli oxidizes NADH with either dichlorophenolindophenol (DCIP). ferricyanide, or menadione as electron acceptors, with values for NADH are similar with the three electron acceptors (approximately 50 muM). The purified enzyme contains no flavin and has an absolute requirement for FAD, with Km values around 4 muM. The pH optimum of the enzyme appears to be between 6.5 and 7; the optimum is difficult to establish because of nonenzymatic reduction of DCIP at the lower pH values. Potassium cyanide stimulates the DCIP reductase activity about 2-fold, but has no effect on ferricyanide reductase. The enzyme exhibits hyperbolic kinetics with respect to NADH concentration in both the ferricyanide and DCIP reductase assays, but cooperatively is seen in the menadione reductase reaction. NAD+ is an effective competitive inhibitor of the reaction (Ki congruent to 20 muM); in the presence of NAD+, the NADH saturation curve becomes cooperative, even in the DCIP reductase assay. Many adenine containing nucleotides are competitive inhibitors of the enzyme. The apparent Ki values for these nucleotides as inhibitors of the purified enzyme, the membrane-bound NADH dehydrogenase, and the NADH oxidase are equivalent. An examination of inhibitory effects of a series of adenine nucleotides suggests that the inhibitors act as analogues of NAD+, which is the true physiological inhibitor. The results suggest that the enzyme in situ is always partially inhibited by the levels of NAD- in the E coli cell, and thus behaves in a cooperative fashion to changes in the NAD+/NADH ratio. An antibody has been elicited against the purified NADH dehydrogenase. Immunodiffusion and crossed immunoelectrophoresis show that the antibody is directed principally against the NADH dehydrogenase, with some activity against minor contaminants in the purified preparation. The antibody inhibits NADH dehydrogenase activity 50% at saturating levels. When this antibody preparation is used to examine solubilized membrane preparations, two major immunoprecipitates are found. A parallel inhibition of the membrane-bound NADH dehydrogenase and NADH oxidase activities is seen, supporting the hypothesis that the purified enzyme is indeed a component of the respiratory chain-dependent NADH oxidase pathway."}
{"id": "PMID:9409", "title": "Aspartate transcarbamylase of Escherichia coli. Heterogeneity of binding sites for carbamyl phosphate and fluorinated analogs of carbamyl phosphate.", "content": "Some preparations of both native aspartate transcarbamylase from Escherichia coli and catalytic subunit have fewer tight binding sites per oligomer for carbamyl-P than the number of catalytic peptide chains. In contrast, the number of sites for the tight-binding inhibitor N-(phosphonacetyl)-L-aspartate does equal the number of catalytic chains in each case. Binding of the labile carbamyl-P was determined using rapid gel filtration, with conversion to stable carbamyl-L-aspartate during collection. Native enzyme (six catalytic chains) obtained from cells grown under the conditions of J.C. Gerhart and H. Holoubek (J. Biol. Chem. (1967) 242, 2886-2892) has 5.4 tight sites for carbamyl-P at pH 8.0 (KD = 9.9 muM), whereas native enzyme from cells grown with higher concentrations of glucose, uracil, and histidine (to yield more enzyme per unit volume of culture) has only 1.9 tight sites at pH 8.0 (KD = 4.6 muM) and only 2.3 tight sites at pH 7.0 (KD = 2.6 muM). At pH 8.0, catalytic subunit (three catalytic chains) obtained from the former native enzyme has 2.2 tight sites for carbamyl-P (KD = 2.4 muM) and the number of sites is 2.3 in the presence of 35 mM succinate, whereas catalytic subunit obtained from the latter native enzyme has 1.8 tight sites (KD = 3.6 muM) in the absence of succinate and 2.3 tight sites in its presence. The number of tight binding sites is also less than the number of subunit peptide chains in 19F nuclear magnetic resonance experiments performed with catalytic subunit and two fluorinated analogs of carbamyl-P at comparable concentrations of analogs and active sites. A model is proposed in which incomplete removal of formylmethionine from the NH2 termini of the enzyme under conditions of extreme depression affects affinity for ligands.", "contents": "Aspartate transcarbamylase of Escherichia coli. Heterogeneity of binding sites for carbamyl phosphate and fluorinated analogs of carbamyl phosphate. Some preparations of both native aspartate transcarbamylase from Escherichia coli and catalytic subunit have fewer tight binding sites per oligomer for carbamyl-P than the number of catalytic peptide chains. In contrast, the number of sites for the tight-binding inhibitor N-(phosphonacetyl)-L-aspartate does equal the number of catalytic chains in each case. Binding of the labile carbamyl-P was determined using rapid gel filtration, with conversion to stable carbamyl-L-aspartate during collection. Native enzyme (six catalytic chains) obtained from cells grown under the conditions of J.C. Gerhart and H. Holoubek (J. Biol. Chem. (1967) 242, 2886-2892) has 5.4 tight sites for carbamyl-P at pH 8.0 (KD = 9.9 muM), whereas native enzyme from cells grown with higher concentrations of glucose, uracil, and histidine (to yield more enzyme per unit volume of culture) has only 1.9 tight sites at pH 8.0 (KD = 4.6 muM) and only 2.3 tight sites at pH 7.0 (KD = 2.6 muM). At pH 8.0, catalytic subunit (three catalytic chains) obtained from the former native enzyme has 2.2 tight sites for carbamyl-P (KD = 2.4 muM) and the number of sites is 2.3 in the presence of 35 mM succinate, whereas catalytic subunit obtained from the latter native enzyme has 1.8 tight sites (KD = 3.6 muM) in the absence of succinate and 2.3 tight sites in its presence. The number of tight binding sites is also less than the number of subunit peptide chains in 19F nuclear magnetic resonance experiments performed with catalytic subunit and two fluorinated analogs of carbamyl-P at comparable concentrations of analogs and active sites. A model is proposed in which incomplete removal of formylmethionine from the NH2 termini of the enzyme under conditions of extreme depression affects affinity for ligands."}
{"id": "PMID:9410", "title": "Evidence from 13C NMR for protonation of carbamyl-P and N-(phosphonacetyl)-L-aspartate in the active site of aspartate transcarbamylase.", "content": "Nuclear magnetic resonance has been used to study the binding of [13C]carbamyl-P (90% enriched) to the catalytic subunit of Escherichia coli aspartate transcarbamylase. Upon forming a binary complex, there is a small change in the chemical shift of the carbonyl carbon resonance, 2 Hz upfield at pH 7.0, indicating that the environments of the carbonyl group in the active site and in water are similar. When succinate, an analog of L-aspartate, is added to form a ternary complex, there is a large downfield change in the chemical shift for carbamyl-P, consistent with interaction between the carbonyl group and a proton donor of the enzyme. The change might also be caused by a ring current froma nearby aromatic amino acid residue. From the pH dependence of this downfield change and from the effects of L-aspartate analogs other than succinate, the form of the enzyme involved is proposed to be an isomerized ternary complex, previously observed in temperature jump and proton NMR studies. The downfield change to chemical shift for carbamyl-P bound to the isomerized complex is 17.7 +/- 1.0 Hz. Using this value, the relative ability of other four-carbon dicarboxylic acids to form isomerized ternary complexes with the enzyme and carbamyl-P has been evaluated quantitatively. The 13C peak for the transition state analog N-(phosphonacetyl)-L-aspartate (PALA), 90% enriched specifically at the amide carbonyl group, is shifted 20 Hz downfield of the peak for free PALA upon binding to the catalytic subunit at pH 7.0. In contrast, the peak for [1-13C] phosphonaceatmide shifts upfield by about 6 Hz upon binding. Since PALA induces isomerization of the enzyme and phosphonacetamide does not, these data provide further evidence consistent with protonation of the carbonyl group only upon isomerization. The degrees of protonation is strong acids of the carbonyl groups of PALA, phosphonacetamide and urethan (a model for the labile carbamyl-P) have been determined, as have the chemical shifts for these compounds upon full protonation. From these data it is calculated that the amide carbonyl groups of carbamyl-P and PALA might be protonated to a maximum of about 20% in the isomerized complexes at pH 7.0. The change in conformation of the enzyme-carbamyl-P complex upon binding L-aspartate, previously proposed to aid catalysis by compressing the two substrates together in the active site, may be accompanied by polarization of the C=O bond, making this ordinarily unreactive group a much better electrophile. A keto analog of PALA, 4,5-dicarboxy-2-ketopentyl phosphonate, also binds tightly to the catalytic subunit and induces a very similar conformational change, whereas an alcohol analog, 4,5-dicarboxy-2-hydroxypentyl phosphonate, does not bind tightly, indicating the critical importance of an unhindered carbonyl group with trigonal geometry.", "contents": "Evidence from 13C NMR for protonation of carbamyl-P and N-(phosphonacetyl)-L-aspartate in the active site of aspartate transcarbamylase. Nuclear magnetic resonance has been used to study the binding of [13C]carbamyl-P (90% enriched) to the catalytic subunit of Escherichia coli aspartate transcarbamylase. Upon forming a binary complex, there is a small change in the chemical shift of the carbonyl carbon resonance, 2 Hz upfield at pH 7.0, indicating that the environments of the carbonyl group in the active site and in water are similar. When succinate, an analog of L-aspartate, is added to form a ternary complex, there is a large downfield change in the chemical shift for carbamyl-P, consistent with interaction between the carbonyl group and a proton donor of the enzyme. The change might also be caused by a ring current froma nearby aromatic amino acid residue. From the pH dependence of this downfield change and from the effects of L-aspartate analogs other than succinate, the form of the enzyme involved is proposed to be an isomerized ternary complex, previously observed in temperature jump and proton NMR studies. The downfield change to chemical shift for carbamyl-P bound to the isomerized complex is 17.7 +/- 1.0 Hz. Using this value, the relative ability of other four-carbon dicarboxylic acids to form isomerized ternary complexes with the enzyme and carbamyl-P has been evaluated quantitatively. The 13C peak for the transition state analog N-(phosphonacetyl)-L-aspartate (PALA), 90% enriched specifically at the amide carbonyl group, is shifted 20 Hz downfield of the peak for free PALA upon binding to the catalytic subunit at pH 7.0. In contrast, the peak for [1-13C] phosphonaceatmide shifts upfield by about 6 Hz upon binding. Since PALA induces isomerization of the enzyme and phosphonacetamide does not, these data provide further evidence consistent with protonation of the carbonyl group only upon isomerization. The degrees of protonation is strong acids of the carbonyl groups of PALA, phosphonacetamide and urethan (a model for the labile carbamyl-P) have been determined, as have the chemical shifts for these compounds upon full protonation. From these data it is calculated that the amide carbonyl groups of carbamyl-P and PALA might be protonated to a maximum of about 20% in the isomerized complexes at pH 7.0. The change in conformation of the enzyme-carbamyl-P complex upon binding L-aspartate, previously proposed to aid catalysis by compressing the two substrates together in the active site, may be accompanied by polarization of the C=O bond, making this ordinarily unreactive group a much better electrophile. A keto analog of PALA, 4,5-dicarboxy-2-ketopentyl phosphonate, also binds tightly to the catalytic subunit and induces a very similar conformational change, whereas an alcohol analog, 4,5-dicarboxy-2-hydroxypentyl phosphonate, does not bind tightly, indicating the critical importance of an unhindered carbonyl group with trigonal geometry."}
{"id": "PMID:9411", "title": "Oxidation of p-cresol by horseradish peroxidase compound I.", "content": "Rate constants for the reaction between horseradish peroxidase compound I and p-cresol have been determined at several values of pH between 2.98 and 10.81. These rate constants were used to construct a log (rate) versus pH profile from which it is readily seen that the most reactive form of the enzyme is its most basic form within this pH range so that base catalysis is occurring. At the maximum rate a second order rate constant of (5.1 +/- 0.3) x 10(-7) M-1 s-1 at 25 degrees is obtained. The activation energy of the reaction at the maximum rate was determined from an Arrhenius plot to be 5.0 +/- 0.5 kcal/mol. Evidence for an exception to the generally accepted enzymatic cycle of horseradish peroxidase is presented. One-half molar equivalent of p-cresol can convert compound I quantitatively to compound II at high pH, whereas usually this step requires 1 molar equivalent of reductant. The stoichiometry of this reaction is pH-dependent.", "contents": "Oxidation of p-cresol by horseradish peroxidase compound I. Rate constants for the reaction between horseradish peroxidase compound I and p-cresol have been determined at several values of pH between 2.98 and 10.81. These rate constants were used to construct a log (rate) versus pH profile from which it is readily seen that the most reactive form of the enzyme is its most basic form within this pH range so that base catalysis is occurring. At the maximum rate a second order rate constant of (5.1 +/- 0.3) x 10(-7) M-1 s-1 at 25 degrees is obtained. The activation energy of the reaction at the maximum rate was determined from an Arrhenius plot to be 5.0 +/- 0.5 kcal/mol. Evidence for an exception to the generally accepted enzymatic cycle of horseradish peroxidase is presented. One-half molar equivalent of p-cresol can convert compound I quantitatively to compound II at high pH, whereas usually this step requires 1 molar equivalent of reductant. The stoichiometry of this reaction is pH-dependent."}
{"id": "PMID:9412", "title": "Stoichiometry of the reaction between horseradish peroxidase and p-cresol.", "content": "Over a wide range of pH horseradish peroxidase compound I can be reduced quantitatively via compound II to the native enzyme by only 1 molar equivalent of p-cresol. Since 2 molar equivalents of electrons are required for the single turnover of the enzymatic cycle, p-cresol behaves as a 2-electron reductant. With p-cresol and compound I in a 1:1 ratio compound II and p-methylphenoxy radicals are obtained in the transient state. Compound II is then reduced to the native enzyme. A possible explanation for the facile reduction of compound II involves reaction with the dimerization product of these radicals, 1/2 molar equivalent of 2,2'-dihydroxy-5,5'-dimethylbiphenyl. If only 1/2 molar equivalent of p-cresol is present, than at high pH the reduction stops at compound II. The major steady state peroxidase oxidation product of p-cresol (with p-cresol in large excess compared to the enzyme concentration) is Pummerer's ketone. Pummerer's ketone is only reactive at pH values greater than about 9 where significant amounts of the enol can be formed via the enolate anion. Therefore, in alkaline solution it is reactive with compound I, but not with compound II, which is converted into an unreactive basic form. These results indicate that Pummerer's ketone cannot be the intermediate free radical product responsible for reducing compound II in the single turnover experiments. It is postulated that Pummerer's ketone is formed only in the steady state by the reaction of the p-methylphenoxy radical with excess p-cresol.", "contents": "Stoichiometry of the reaction between horseradish peroxidase and p-cresol. Over a wide range of pH horseradish peroxidase compound I can be reduced quantitatively via compound II to the native enzyme by only 1 molar equivalent of p-cresol. Since 2 molar equivalents of electrons are required for the single turnover of the enzymatic cycle, p-cresol behaves as a 2-electron reductant. With p-cresol and compound I in a 1:1 ratio compound II and p-methylphenoxy radicals are obtained in the transient state. Compound II is then reduced to the native enzyme. A possible explanation for the facile reduction of compound II involves reaction with the dimerization product of these radicals, 1/2 molar equivalent of 2,2'-dihydroxy-5,5'-dimethylbiphenyl. If only 1/2 molar equivalent of p-cresol is present, than at high pH the reduction stops at compound II. The major steady state peroxidase oxidation product of p-cresol (with p-cresol in large excess compared to the enzyme concentration) is Pummerer's ketone. Pummerer's ketone is only reactive at pH values greater than about 9 where significant amounts of the enol can be formed via the enolate anion. Therefore, in alkaline solution it is reactive with compound I, but not with compound II, which is converted into an unreactive basic form. These results indicate that Pummerer's ketone cannot be the intermediate free radical product responsible for reducing compound II in the single turnover experiments. It is postulated that Pummerer's ketone is formed only in the steady state by the reaction of the p-methylphenoxy radical with excess p-cresol."}
{"id": "PMID:9413", "title": "Active site chlorination of D-amino acid oxidase by N-chloro-D-leucine.", "content": "N-Chloro-D-leucine is an irreversible inhibitor or D-amino acid oxidase on a time scale of seconds. Studies with N-[36C]chloro-D-leucine, N-chloro-D-[1-14C]leucine and N-chloro-D-[4,5-3H]leucine show that the modified enzyme has been chlorinated at a site, or sites, on the apoenzyme. The 36Cl measurements agree with titrations of catalytic activity in showing that two chlorine equivalents are incorporated per active site flavin. Kinetically, the interaction with N-chloro-D-leucine behaves in a manner which is consistent with consecutive chlorinations of an amino acid residue, or residues, in the active site region by the first 2 molecules of N-chloro-D-leucine to be processed by the enzyme. The effect of chlorination of the enzyme on the steady state parameters for oxidation of D-alanine is entirely explained by a single perturbation, namely, a 1000-fold reduction in the specific rate of flavin reduction as measured directly by rapid reaction techniques.", "contents": "Active site chlorination of D-amino acid oxidase by N-chloro-D-leucine. N-Chloro-D-leucine is an irreversible inhibitor or D-amino acid oxidase on a time scale of seconds. Studies with N-[36C]chloro-D-leucine, N-chloro-D-[1-14C]leucine and N-chloro-D-[4,5-3H]leucine show that the modified enzyme has been chlorinated at a site, or sites, on the apoenzyme. The 36Cl measurements agree with titrations of catalytic activity in showing that two chlorine equivalents are incorporated per active site flavin. Kinetically, the interaction with N-chloro-D-leucine behaves in a manner which is consistent with consecutive chlorinations of an amino acid residue, or residues, in the active site region by the first 2 molecules of N-chloro-D-leucine to be processed by the enzyme. The effect of chlorination of the enzyme on the steady state parameters for oxidation of D-alanine is entirely explained by a single perturbation, namely, a 1000-fold reduction in the specific rate of flavin reduction as measured directly by rapid reaction techniques."}
{"id": "PMID:9416", "title": "Spore germination promoter of Dictyostelium discoideum excreted by Aerobacter aerogenes.", "content": "The nutrient medium in which Aerobacter aerogenes was grown, contains a spore germination promoter (SGP) for the cellular slime mould Dictyostelium discoideum. SGP can cuase synchronous spore germination in a short time, and triggers the germination process in just a few minutes. Germination-promoting capacity of SGP decreases as it comes in contact with increasing number of spores. When spores activated by SGP are stored at 4 degrees C, they gradually return to the dormant state. SGP is comparatively heat-stable, but is unstable at pH above 10 or under 3.", "contents": "Spore germination promoter of Dictyostelium discoideum excreted by Aerobacter aerogenes. The nutrient medium in which Aerobacter aerogenes was grown, contains a spore germination promoter (SGP) for the cellular slime mould Dictyostelium discoideum. SGP can cuase synchronous spore germination in a short time, and triggers the germination process in just a few minutes. Germination-promoting capacity of SGP decreases as it comes in contact with increasing number of spores. When spores activated by SGP are stored at 4 degrees C, they gradually return to the dormant state. SGP is comparatively heat-stable, but is unstable at pH above 10 or under 3."}
{"id": "PMID:9414", "title": "Surgical treatment of dissecting aortic aneurysm. Twenty years' experience.", "content": "Early and late results of 40 cases of dissecting aortic aneurysm were reported. 1. Result of 6 cases with acute dissection was as follows: two of three surgical patients survived, whereas all three with drug therapy died. Surgical treatment is preferred for the dissection of the ascending aorta or the arch. Some problems of the postoperative morbidity were discussed: 2. Whether medically treated or surgically, chronic dissection of the descending aorta or the abdominal aorta had better prognosis than that of the other site. Chronic dissection with no saccular enlargement had good prognosis. More than 10 years survival is to be expected. The operative result for the chronic aortic dissection was poor, especially in case of the involved ascending aorta and arch. For the saccular enlargement of the pseudolumen wrapping method with or without the resection might be the preferable procedure to avoid early rupture.", "contents": "Surgical treatment of dissecting aortic aneurysm. Twenty years' experience. Early and late results of 40 cases of dissecting aortic aneurysm were reported. 1. Result of 6 cases with acute dissection was as follows: two of three surgical patients survived, whereas all three with drug therapy died. Surgical treatment is preferred for the dissection of the ascending aorta or the arch. Some problems of the postoperative morbidity were discussed: 2. Whether medically treated or surgically, chronic dissection of the descending aorta or the abdominal aorta had better prognosis than that of the other site. Chronic dissection with no saccular enlargement had good prognosis. More than 10 years survival is to be expected. The operative result for the chronic aortic dissection was poor, especially in case of the involved ascending aorta and arch. For the saccular enlargement of the pseudolumen wrapping method with or without the resection might be the preferable procedure to avoid early rupture."}
{"id": "PMID:9415", "title": "Aortitis syndrome due to Takayasu's disease. A guideline for the surgical indication.", "content": "Seven cases of aortitis syndrome were surgically treated with good results: Abdominal aortic aneurysm 1, atypical coarctation of aorta 2, aortic valve insufficiency 2, renovascular hypertension 2. Several attentions were paid as following: 1. Operation should be avoided during acute phase of aortitis. 2. Synthetic graft material should be avoided if possible. Autogenous vein is advisable for reconstruction of small-sized artery. 3. Surgical intervention should be performed before the loss of organ function. 4. Hematological consideration is worthwhile to prevent hypercoagulopathy due to aortitis.", "contents": "Aortitis syndrome due to Takayasu's disease. A guideline for the surgical indication. Seven cases of aortitis syndrome were surgically treated with good results: Abdominal aortic aneurysm 1, atypical coarctation of aorta 2, aortic valve insufficiency 2, renovascular hypertension 2. Several attentions were paid as following: 1. Operation should be avoided during acute phase of aortitis. 2. Synthetic graft material should be avoided if possible. Autogenous vein is advisable for reconstruction of small-sized artery. 3. Surgical intervention should be performed before the loss of organ function. 4. Hematological consideration is worthwhile to prevent hypercoagulopathy due to aortitis."}
{"id": "PMID:9421", "title": "Effect of glass on pH-dependent stability of typhoid vaccine.", "content": "Vaccines made from the Ty-2 strain of Salmonella typhosa were tested periodically for stability of pH and of potency. The acetone-treated cultures prepared in buffered saline solutions retained potency beyond 30 months of storage at 0 to 5 C. Similar vaccines in unbuffered saline solutions lost potency coincident with increase of alkalinity. Vaccines packaged in United States Pharmacopeia borosilicate glass vials retained potency and pH stability, whereas those in Type III United States Pharmacopeia soda-lime glass vials were less stable.", "contents": "Effect of glass on pH-dependent stability of typhoid vaccine. Vaccines made from the Ty-2 strain of Salmonella typhosa were tested periodically for stability of pH and of potency. The acetone-treated cultures prepared in buffered saline solutions retained potency beyond 30 months of storage at 0 to 5 C. Similar vaccines in unbuffered saline solutions lost potency coincident with increase of alkalinity. Vaccines packaged in United States Pharmacopeia borosilicate glass vials retained potency and pH stability, whereas those in Type III United States Pharmacopeia soda-lime glass vials were less stable."}
{"id": "PMID:9422", "title": "Latex agglutination in the diagnosis of pneumococcal infection.", "content": "A latex agglutination (LA) method for detection of pneumococcal antigens was evaluated and compared with counterimmunoelectrophoresis (CIE). LA was 2 to 10 times more sensitive than CIE for the detection of purified capsular polysaccharides in defined media, but only when a 1+ or 2+ agglutination reaction was interpreted as positive. LA was much less sensitive than CIE with clinical samples. In 50 cases of pneumococcal pneumonia, antigen was detected in the serum almost twice as often with CIE (40%) as with LA (22%). LA was positive in six cases of pneumonia where CIE was negative; however, in three of these cases, antigen was detected only in undiluted sera, which raised some question about the specificity of the result. With 18 samples of cerebrospinal fluid (CSF) from 11 patients with pneumococcal meningitis, the CIE test was positive more frequenlty (14 samples) than was LA (11 samples). Moreover, antigen was detected in CSF by LA in only one additional patient than was positive by CIE alone. There was one false-positive LA reaction among 45 samples of CSF from patients without pneumococcal infection. Although LA is a less complicated method than CIE, it is not a sensitive test for pneumococcal antigens and would be of little value as a routine diagnostic method.", "contents": "Latex agglutination in the diagnosis of pneumococcal infection. A latex agglutination (LA) method for detection of pneumococcal antigens was evaluated and compared with counterimmunoelectrophoresis (CIE). LA was 2 to 10 times more sensitive than CIE for the detection of purified capsular polysaccharides in defined media, but only when a 1+ or 2+ agglutination reaction was interpreted as positive. LA was much less sensitive than CIE with clinical samples. In 50 cases of pneumococcal pneumonia, antigen was detected in the serum almost twice as often with CIE (40%) as with LA (22%). LA was positive in six cases of pneumonia where CIE was negative; however, in three of these cases, antigen was detected only in undiluted sera, which raised some question about the specificity of the result. With 18 samples of cerebrospinal fluid (CSF) from 11 patients with pneumococcal meningitis, the CIE test was positive more frequenlty (14 samples) than was LA (11 samples). Moreover, antigen was detected in CSF by LA in only one additional patient than was positive by CIE alone. There was one false-positive LA reaction among 45 samples of CSF from patients without pneumococcal infection. Although LA is a less complicated method than CIE, it is not a sensitive test for pneumococcal antigens and would be of little value as a routine diagnostic method."}
{"id": "PMID:9423", "title": "Optimal conditions for elution of hepatitis B antigen after absorption onto colloidal silica.", "content": "Hepatitis B surface antigen (HBSAg) adsorbed from sera onto colloidal silica could be completely eluted through the use of 0.25% sodium deoxycholate in 0.01 M borax, pH 9.3, at 56 degrees C. The HBSAg recovered in the eluate represented 100% of that present in the original serum, and it was contaminated by only trace amounts of serum proteins (in decreasing amounts: beta-lipoprotein, immunoglobulin G, albumin). This preliminary step greatly facilitates purification of large amounts of HBSAg and provides small volumes of highly concentrated material for subsequent purification by density gradient centrifugation.", "contents": "Optimal conditions for elution of hepatitis B antigen after absorption onto colloidal silica. Hepatitis B surface antigen (HBSAg) adsorbed from sera onto colloidal silica could be completely eluted through the use of 0.25% sodium deoxycholate in 0.01 M borax, pH 9.3, at 56 degrees C. The HBSAg recovered in the eluate represented 100% of that present in the original serum, and it was contaminated by only trace amounts of serum proteins (in decreasing amounts: beta-lipoprotein, immunoglobulin G, albumin). This preliminary step greatly facilitates purification of large amounts of HBSAg and provides small volumes of highly concentrated material for subsequent purification by density gradient centrifugation."}
{"id": "PMID:9424", "title": "Immune response to acute otitis media: association between middle ear fluid antibody and the clearing of clinical infection.", "content": "Clearing of the middle ear fluid in patients with acute otitis media due to Streptococcus pneumoniae or Haemophilus influenzae was significantly associated with the presence and concentration of specific antibody in the middle ear fluid at the time of diagnosis.", "contents": "Immune response to acute otitis media: association between middle ear fluid antibody and the clearing of clinical infection. Clearing of the middle ear fluid in patients with acute otitis media due to Streptococcus pneumoniae or Haemophilus influenzae was significantly associated with the presence and concentration of specific antibody in the middle ear fluid at the time of diagnosis."}
{"id": "PMID:9425", "title": "Metalloproteases of human articular cartilage that digest cartilage proteoglycan at neutral and acid pH.", "content": "Extracts of human articular cartilage contain proteases capable of degrading the proteoglycan component of cartilage matrix at neutral and acid pH. These enzymes have been partially purified by ion exchange chromotography and characterized by disc electrophoresis, inhibition patterns, and action of proteoglycan. Three distinct metalloproteases are described. A neutral protease that digests proteoglycan subunit optimally at pH 7.25 has been purified up to 900-fold. It is strongly inhibited by o-phenanthroline, alpha-2-macroglobulin, and egg white, and to a lesser extent by D-penicillamine and EDTA. Inhibition by chelating agents is reversed by cobalt, zinc, and ferrous ions. Two acid metalloproteases, distinct from cathespins B1, D, and F, digest proteoglycan subunit at pH 4.5 and 5.5. Both are inhibited by o-phenanthroline and activity is restored by cobalt, zinc, or ferrous ions. With electron microscopy, it was found that cartilage slices were depleted of ruthenium red-staining matrix proteoglycan after incubation in vitro with a partially purified cartilage extract at neutral pH. Sedimentation, gel chromatography, sodium dodecyl sulfate-gel electrophoresis, and immuno-diffusion studies of digests of isolated proteoglycan fraction produced by the partially purified cartilage extract at neutral and acid pH confirmed that the cartilage enzymes act only on the protein component of proteoglycan subunit, producing fragments with 5 to 12 chondroitin sulfate chains. The link proteins were not digested.", "contents": "Metalloproteases of human articular cartilage that digest cartilage proteoglycan at neutral and acid pH. Extracts of human articular cartilage contain proteases capable of degrading the proteoglycan component of cartilage matrix at neutral and acid pH. These enzymes have been partially purified by ion exchange chromotography and characterized by disc electrophoresis, inhibition patterns, and action of proteoglycan. Three distinct metalloproteases are described. A neutral protease that digests proteoglycan subunit optimally at pH 7.25 has been purified up to 900-fold. It is strongly inhibited by o-phenanthroline, alpha-2-macroglobulin, and egg white, and to a lesser extent by D-penicillamine and EDTA. Inhibition by chelating agents is reversed by cobalt, zinc, and ferrous ions. Two acid metalloproteases, distinct from cathespins B1, D, and F, digest proteoglycan subunit at pH 4.5 and 5.5. Both are inhibited by o-phenanthroline and activity is restored by cobalt, zinc, or ferrous ions. With electron microscopy, it was found that cartilage slices were depleted of ruthenium red-staining matrix proteoglycan after incubation in vitro with a partially purified cartilage extract at neutral pH. Sedimentation, gel chromatography, sodium dodecyl sulfate-gel electrophoresis, and immuno-diffusion studies of digests of isolated proteoglycan fraction produced by the partially purified cartilage extract at neutral and acid pH confirmed that the cartilage enzymes act only on the protein component of proteoglycan subunit, producing fragments with 5 to 12 chondroitin sulfate chains. The link proteins were not digested."}
{"id": "PMID:9426", "title": "The particulate superoxide-forming system from human neutrophils. Properties of the system and further evidence supporting its participation in the respiratory burst.", "content": "Studies were performed to characterize the previously reported particulate O2--forming system from human neutrophils. Of eight reducing agents examined, including glutathione, ascorbic acid, and intermediates of the glycolytic and hexose monophosphate shunt pathways, only the pyridine nucleotides could serve as electron donors. At 0.1 mM pyridine nucleotide, O2- production was relatively independent of pH. The Km for NADH was approximately 0.7 mM regardless of pH, while with NADPH the Km varied from 0.02 mM at pH 6.0 to 0.3 mM at pH 7.5. The molar ratio of NADPH oxidized to O2- produced was consistent with the reaction: NADPH + 2 O2- leads to NADP+ H+; the product nucleotide was shown enzymatically to be NADP. O2- production was not inhibited by CN-, Na-, EDTA, or 1,10-phenanthroline. Particulate O2- production accounted for 35% of the oxygen taken up during the respiratory burst by an equivalent number of intact neutrophils. Greatly diminished O2- production was seen with particles prepared from cells obtained from three patients with chronic granulomatous disease, with 2.5 mM NADPH as electron donor. With 5.0 mM NADH similar observations were made with particles from two of the patients, but with this nucelotide, O2- production was only slightly reduced in the third case. The evidence available suggests that this particulate O2- -forming system is the one responsible for the respiratory burst in activated neutrophils. The relationship between this system and other O2- -forming system found in human neutrophils is discussed.", "contents": "The particulate superoxide-forming system from human neutrophils. Properties of the system and further evidence supporting its participation in the respiratory burst. Studies were performed to characterize the previously reported particulate O2--forming system from human neutrophils. Of eight reducing agents examined, including glutathione, ascorbic acid, and intermediates of the glycolytic and hexose monophosphate shunt pathways, only the pyridine nucleotides could serve as electron donors. At 0.1 mM pyridine nucleotide, O2- production was relatively independent of pH. The Km for NADH was approximately 0.7 mM regardless of pH, while with NADPH the Km varied from 0.02 mM at pH 6.0 to 0.3 mM at pH 7.5. The molar ratio of NADPH oxidized to O2- produced was consistent with the reaction: NADPH + 2 O2- leads to NADP+ H+; the product nucleotide was shown enzymatically to be NADP. O2- production was not inhibited by CN-, Na-, EDTA, or 1,10-phenanthroline. Particulate O2- production accounted for 35% of the oxygen taken up during the respiratory burst by an equivalent number of intact neutrophils. Greatly diminished O2- production was seen with particles prepared from cells obtained from three patients with chronic granulomatous disease, with 2.5 mM NADPH as electron donor. With 5.0 mM NADH similar observations were made with particles from two of the patients, but with this nucelotide, O2- production was only slightly reduced in the third case. The evidence available suggests that this particulate O2- -forming system is the one responsible for the respiratory burst in activated neutrophils. The relationship between this system and other O2- -forming system found in human neutrophils is discussed."}
{"id": "PMID:9432", "title": "Characterization and modification of permselective properties of apatite membranes.", "content": "Compressed apatite disks were used as models for tooth enamel. Their permselective properties were studied as functions of the pH of the gradient solutions, the composition of the apatites, and the pretreatments with anionic phosphate compounds and cationic proteins. The results are discussed in relation to the caries mechanisms.", "contents": "Characterization and modification of permselective properties of apatite membranes. Compressed apatite disks were used as models for tooth enamel. Their permselective properties were studied as functions of the pH of the gradient solutions, the composition of the apatites, and the pretreatments with anionic phosphate compounds and cationic proteins. The results are discussed in relation to the caries mechanisms."}
{"id": "PMID:9430", "title": "Capacity of buffers to inhibit acid production within dental plaque.", "content": "An oral radiotelemetric technique was used to determine whether a range of efficient buffers had the capacity to control the levels of hydrogen ions within dental plaque in the presence of sucrose. It was found that the buffers failed to control both the intensity and duration of the acid produced.", "contents": "Capacity of buffers to inhibit acid production within dental plaque. An oral radiotelemetric technique was used to determine whether a range of efficient buffers had the capacity to control the levels of hydrogen ions within dental plaque in the presence of sucrose. It was found that the buffers failed to control both the intensity and duration of the acid produced."}
{"id": "PMID:9431", "title": "Comparison of dextranases for their possible use in eliminating dental plaque.", "content": "Dextranases produced by P lilacinum NRRL 896 and NRRL 895 and by P funiculosum NRRL 1768 were studied for their possible incorporation into a dental plaque elimination system. The following properties of the enzymes were compared: effect of the pH level on the activity and the stability of the enzymes on the acid side of the pH range; molecular weight; affinity to Sephadex G-25 which served as a model for insoluble dextran in plaques; and the extent of hydrolytic action on dextrans containing alpha-1,3, alpha-1,4 and alpha-1,6 bonds in various proportions. The enzyme of P funiculosum NRRL 1768 certainly has its limitations as a plaque-degrading enzyme, for example, diminished activity at a high pH level and lack of activity on alpha-1,3 bonds. However, from our studies, and from a survey of the relevant literature with respect to the aforementioned properties in other dextranases, the enzyme of P funiculosum NRRL 1768 emerges as a suitable choice for incorporation as dextranase, possibly together with other enzymes, into an enzymatic dental plaque elimination system.", "contents": "Comparison of dextranases for their possible use in eliminating dental plaque. Dextranases produced by P lilacinum NRRL 896 and NRRL 895 and by P funiculosum NRRL 1768 were studied for their possible incorporation into a dental plaque elimination system. The following properties of the enzymes were compared: effect of the pH level on the activity and the stability of the enzymes on the acid side of the pH range; molecular weight; affinity to Sephadex G-25 which served as a model for insoluble dextran in plaques; and the extent of hydrolytic action on dextrans containing alpha-1,3, alpha-1,4 and alpha-1,6 bonds in various proportions. The enzyme of P funiculosum NRRL 1768 certainly has its limitations as a plaque-degrading enzyme, for example, diminished activity at a high pH level and lack of activity on alpha-1,3 bonds. However, from our studies, and from a survey of the relevant literature with respect to the aforementioned properties in other dextranases, the enzyme of P funiculosum NRRL 1768 emerges as a suitable choice for incorporation as dextranase, possibly together with other enzymes, into an enzymatic dental plaque elimination system."}
{"id": "PMID:9437", "title": "Histamine hypersensitivity in mice induced by Bordetella pertussis or pharmacologic beta adrenergic blockade. Effects of adrenergic, cholinergic, and other drugs.", "content": "The effects of prostaglandin E1, E2, F2alpha (PGE2 PGF2alpha), isoproterenol, epinephrine, norepinephrine, salbutamol, practolol, atropine, aminophylline, and corticosterone on the hypersensitivity to anaphylaxis, histamine, and serotonin in Bordetella pertussis-treated mice and propranolol-treated mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected with pertussis vaccine intravenously 4 days before challenge with antigen, histamine, or serotonin. Alternatively, instead of pertussis vaccine, propranolol was injected intraperitoneally 45 min before histamine challenge. Test drugs were administered intraperitoneally 15 min before challenge. PGE1 and PGE2 at a narrow range of between 10 and 100 mug and epinephrine at 100 mug protected both pertussis- and propranolol-treated mice. Isoproterenol (25 mug) and aminophilline (800 mug) protected beta-blocked mice, but did not protect pertussis-treated mice even with very high doses (1,000 and 3,2000 mug, respectively), although salbutamol (500 mug) did. PGF2alpha, norepinephrine, and atropine were not protective at all. Practolol, a beta 1-blocker, given intraperitoneally 30 min before histamine neither sensitized normal mice nor changed the effect of isoproterenol or salbutamol in pertussis-treated mice. Corticosterone 10 mg/kg reduced the number of deaths from histamine in beta-blocked mice, but not in pertussis-treated mice. The protective effect is discussed in connection with probable effects of the drugs on intracellular cyclic adenosine monophosphate (cAMP) levels.", "contents": "Histamine hypersensitivity in mice induced by Bordetella pertussis or pharmacologic beta adrenergic blockade. Effects of adrenergic, cholinergic, and other drugs. The effects of prostaglandin E1, E2, F2alpha (PGE2 PGF2alpha), isoproterenol, epinephrine, norepinephrine, salbutamol, practolol, atropine, aminophylline, and corticosterone on the hypersensitivity to anaphylaxis, histamine, and serotonin in Bordetella pertussis-treated mice and propranolol-treated mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected with pertussis vaccine intravenously 4 days before challenge with antigen, histamine, or serotonin. Alternatively, instead of pertussis vaccine, propranolol was injected intraperitoneally 45 min before histamine challenge. Test drugs were administered intraperitoneally 15 min before challenge. PGE1 and PGE2 at a narrow range of between 10 and 100 mug and epinephrine at 100 mug protected both pertussis- and propranolol-treated mice. Isoproterenol (25 mug) and aminophilline (800 mug) protected beta-blocked mice, but did not protect pertussis-treated mice even with very high doses (1,000 and 3,2000 mug, respectively), although salbutamol (500 mug) did. PGF2alpha, norepinephrine, and atropine were not protective at all. Practolol, a beta 1-blocker, given intraperitoneally 30 min before histamine neither sensitized normal mice nor changed the effect of isoproterenol or salbutamol in pertussis-treated mice. Corticosterone 10 mg/kg reduced the number of deaths from histamine in beta-blocked mice, but not in pertussis-treated mice. The protective effect is discussed in connection with probable effects of the drugs on intracellular cyclic adenosine monophosphate (cAMP) levels."}
{"id": "PMID:9454", "title": "A comparison of ATP-degrading enzyme activities in rat incisor odontoblasts.", "content": "In active odontoblasts from the rat incisor, used as a model system for biologic calcification, two distinguishable enzyme activities capable of degrading adenosine monophosphate (ATP) exist. Once can be inhibited ny 1-tetramisole, (+/-)-2,3,5,6,-tetrahydro-6-phenylimidazo (2.1B) THIAZOLE HYDROCHLORIDE (Levamisol) and (+/-)-6(m-bromophenyl)-5.6-dehydroimidazo (2.1-b) thiazole oxalate (R823) and is probably identical with nonspecific alkaline phosphatase (EC 3.1.3.1). The activity of the other enzyme, named Ca2+-ATPase, is dependent on the presence of Ca2+ or Mg2+ and is activated by these ions. The pH optimum of Ca2+-ATPase is 9.8. The Ca2+-ATPase is unaffected by Levamisole, R 8231, ouabain, ruthenium red, Na+ and K+ ions. Maximal activity was found against ATP, whereas adenosine diphosphate, guanosine triphosphate, inosine triphosphate and adensoine monophosphate were hydrolysed at lower rate. It may be speculated that the Ca2+-ATPase is concerned with the transmembranous transport of Ca2+ ions to the mineralization front.", "contents": "A comparison of ATP-degrading enzyme activities in rat incisor odontoblasts. In active odontoblasts from the rat incisor, used as a model system for biologic calcification, two distinguishable enzyme activities capable of degrading adenosine monophosphate (ATP) exist. Once can be inhibited ny 1-tetramisole, (+/-)-2,3,5,6,-tetrahydro-6-phenylimidazo (2.1B) THIAZOLE HYDROCHLORIDE (Levamisol) and (+/-)-6(m-bromophenyl)-5.6-dehydroimidazo (2.1-b) thiazole oxalate (R823) and is probably identical with nonspecific alkaline phosphatase (EC 3.1.3.1). The activity of the other enzyme, named Ca2+-ATPase, is dependent on the presence of Ca2+ or Mg2+ and is activated by these ions. The pH optimum of Ca2+-ATPase is 9.8. The Ca2+-ATPase is unaffected by Levamisole, R 8231, ouabain, ruthenium red, Na+ and K+ ions. Maximal activity was found against ATP, whereas adenosine diphosphate, guanosine triphosphate, inosine triphosphate and adensoine monophosphate were hydrolysed at lower rate. It may be speculated that the Ca2+-ATPase is concerned with the transmembranous transport of Ca2+ ions to the mineralization front."}
{"id": "PMID:9455", "title": "Detection of A1A2 and A2AAm1 heterozygotes among human A blood group phenotypes.", "content": "From the variations of alpha-N-acetylgalactosaminyltransferases activities with the pH, evidence was obtained for the recognition of A1A2 heterozygotes in normal A blood group sera. Besides, unusual transferase properties associated with two A2 sera from individuals out of AAm1 siblings, lead to the identification of the very infrequent A2AAm1 genotypes. These results strongly support the simultaneous coexistence of both A1 and A2 transferases in heterozygotes' sera, and bring some new information on the genetical background of the Am phenotype. The meaning of transferase properties directly determined on whole sera is briefly discussed.", "contents": "Detection of A1A2 and A2AAm1 heterozygotes among human A blood group phenotypes. From the variations of alpha-N-acetylgalactosaminyltransferases activities with the pH, evidence was obtained for the recognition of A1A2 heterozygotes in normal A blood group sera. Besides, unusual transferase properties associated with two A2 sera from individuals out of AAm1 siblings, lead to the identification of the very infrequent A2AAm1 genotypes. These results strongly support the simultaneous coexistence of both A1 and A2 transferases in heterozygotes' sera, and bring some new information on the genetical background of the Am phenotype. The meaning of transferase properties directly determined on whole sera is briefly discussed."}
{"id": "PMID:9456", "title": "Adrenergic mechanisms and the adenyl cyclase system in atopic dermatitis.", "content": "Patients with atopic dermatitis have abnormal autonomic responses of the arterioles, pilomotor smooth muscle, and sweat glands. Their lesions have been reported to contain increased amounts of the neurohumors, acetylcholine and norepinephrine, as well as increased activity of acetylcholinesterase and catechol-O-methyltransferase. In vitro studies of epidermis show that beta adrenergic agonists fail to evoke the normal inhibition of mitosis of basal cells of patients with atopic dermatitis. Epidermis removed not only from the lesions, but also from normal-appearing skin, responded abnormally. The increase in intracellular levels of cAMP after exposure to catecholamines was similar in normal and atopic epidermis. Lymphocytes and PMN leukocytes isolated from patients with atopic dermatitis show both a decreased physiologic response (glycogenolysis and inhibition of lysosome enzyme release) and a decreased rise in intracellular levels of cAMP upon incubation with beta agonists, but a normal response to PGE1. Cortisol increases the response of lymphocyte adenyl cyclase to both agonists and, in the case of the patients with atopic disease, more than overcomes the depressed response to beta agonists. Because the  leukocytes respond normally to PGE1 and because others have reported normal activities of skin and adenyl cyclase, phosphodiesterase, and protein kinases, we conclude that the step responsible for the diminished beta adrenergic response lies antecedent to the catalytic site of adenyl cyclase.", "contents": "Adrenergic mechanisms and the adenyl cyclase system in atopic dermatitis. Patients with atopic dermatitis have abnormal autonomic responses of the arterioles, pilomotor smooth muscle, and sweat glands. Their lesions have been reported to contain increased amounts of the neurohumors, acetylcholine and norepinephrine, as well as increased activity of acetylcholinesterase and catechol-O-methyltransferase. In vitro studies of epidermis show that beta adrenergic agonists fail to evoke the normal inhibition of mitosis of basal cells of patients with atopic dermatitis. Epidermis removed not only from the lesions, but also from normal-appearing skin, responded abnormally. The increase in intracellular levels of cAMP after exposure to catecholamines was similar in normal and atopic epidermis. Lymphocytes and PMN leukocytes isolated from patients with atopic dermatitis show both a decreased physiologic response (glycogenolysis and inhibition of lysosome enzyme release) and a decreased rise in intracellular levels of cAMP upon incubation with beta agonists, but a normal response to PGE1. Cortisol increases the response of lymphocyte adenyl cyclase to both agonists and, in the case of the patients with atopic disease, more than overcomes the depressed response to beta agonists. Because the  leukocytes respond normally to PGE1 and because others have reported normal activities of skin and adenyl cyclase, phosphodiesterase, and protein kinases, we conclude that the step responsible for the diminished beta adrenergic response lies antecedent to the catalytic site of adenyl cyclase."}
{"id": "PMID:9462", "title": "Coenzyme A derivatives of bile acids-chemical synthesis, purification, and utilization in enzymic preparation of taurine conjugates.", "content": "Synthesis of the coenzyme A derivatives of bile acids by the mixed anyhydride method results in a product that is contaminated by unreacted CoASH and bile acid. These compounds can be purified by Sephadex LH-20 chromatography. In each case, the purified product is free of starting materials and exhibits an equimolar ratio of bile acid, coenzyme A, and thioester bond. Millimolar extinction coefficients were calculated for these compounds as A259 nm, 15.03 +/- 0.58; A232 nm, 7.60 +/- 0.17; and A232 nm for the thioester bond, 4.12 +/- 0.17. These CoA derivatives were hydrolyzed in strongly alkaline solution, but were stable at physiologic temperature and pH. Utilization of these compounds in the enzymic preparation of taurine conjugates of bile acids indicated 94% activity. These purified CoA derivatives may be useful in studying the enzymic conjugation of bile acids.", "contents": "Coenzyme A derivatives of bile acids-chemical synthesis, purification, and utilization in enzymic preparation of taurine conjugates. Synthesis of the coenzyme A derivatives of bile acids by the mixed anyhydride method results in a product that is contaminated by unreacted CoASH and bile acid. These compounds can be purified by Sephadex LH-20 chromatography. In each case, the purified product is free of starting materials and exhibits an equimolar ratio of bile acid, coenzyme A, and thioester bond. Millimolar extinction coefficients were calculated for these compounds as A259 nm, 15.03 +/- 0.58; A232 nm, 7.60 +/- 0.17; and A232 nm for the thioester bond, 4.12 +/- 0.17. These CoA derivatives were hydrolyzed in strongly alkaline solution, but were stable at physiologic temperature and pH. Utilization of these compounds in the enzymic preparation of taurine conjugates of bile acids indicated 94% activity. These purified CoA derivatives may be useful in studying the enzymic conjugation of bile acids."}
{"id": "PMID:9463", "title": "Sphingomyelinase activity at pH 7.4 in human brain and a comparison to activity at pH 5.0.", "content": "A hitherto undescribed sphingomyelinase (sph'ase 7.4) of human brain has been studied in crude and partially purified (3- to 4- fold) extracts of grey matter, and compared to the known sphingomyelinase with an acid pH optimum (sph'ase 5.0). Its specificity for sphingomyelin as substrate is similar to that of sph'ase 5.0, but it differs from sph'ase 5.0 in its pH optimum (7.4 vs 5.0) and in a requirement for Mg2+ for optimal activity. Other properties of sph'ase 7.4 that distinguish it from sph'ase 5.0 include (a) its lack of appreciable solubilization during dialysis of crude homogenates (b) a more marked concentrations in grey matter than in white matter (9- to 13- fold vs 1.5- to 2-fold for sph'ase 5.0); (c) inhibition by Ca2+ and Cd2+ ions, and by EDTA; (D) stimulation by dithiothreitol, and inhibition by cysteine, N-ethylmaleimide, and p-hydroxymercuribenzoate; (e) lack of inhibition by nucleotides (AMP.ADP, and ATP) and by NAD plus NADH; and (f) relative instability to storage or manipulation between -20degrees C and 40degrees C. These differences indicate the SPH'ASE 7.4 is a different enzyme protein from sph'ase 5.0. Unlike sph'ase 5.0, which is widely distributed in mammalian tissues, sph'ase 7.4 occurs predominantly in grey matter and little activity was observed is spleen, liver, or leukocytes. The high levels of this enzyme in brain suggest a role related to the specific functions of this organ or to the need for a more stringent control of sphingomyelin catabolism in brain as compared to other organs.", "contents": "Sphingomyelinase activity at pH 7.4 in human brain and a comparison to activity at pH 5.0. A hitherto undescribed sphingomyelinase (sph'ase 7.4) of human brain has been studied in crude and partially purified (3- to 4- fold) extracts of grey matter, and compared to the known sphingomyelinase with an acid pH optimum (sph'ase 5.0). Its specificity for sphingomyelin as substrate is similar to that of sph'ase 5.0, but it differs from sph'ase 5.0 in its pH optimum (7.4 vs 5.0) and in a requirement for Mg2+ for optimal activity. Other properties of sph'ase 7.4 that distinguish it from sph'ase 5.0 include (a) its lack of appreciable solubilization during dialysis of crude homogenates (b) a more marked concentrations in grey matter than in white matter (9- to 13- fold vs 1.5- to 2-fold for sph'ase 5.0); (c) inhibition by Ca2+ and Cd2+ ions, and by EDTA; (D) stimulation by dithiothreitol, and inhibition by cysteine, N-ethylmaleimide, and p-hydroxymercuribenzoate; (e) lack of inhibition by nucleotides (AMP.ADP, and ATP) and by NAD plus NADH; and (f) relative instability to storage or manipulation between -20degrees C and 40degrees C. These differences indicate the SPH'ASE 7.4 is a different enzyme protein from sph'ase 5.0. Unlike sph'ase 5.0, which is widely distributed in mammalian tissues, sph'ase 7.4 occurs predominantly in grey matter and little activity was observed is spleen, liver, or leukocytes. The high levels of this enzyme in brain suggest a role related to the specific functions of this organ or to the need for a more stringent control of sphingomyelin catabolism in brain as compared to other organs."}
{"id": "PMID:9464", "title": "A stable, radioactive substrate emulsion for assay of lipoprotein lipase.", "content": "A method is described for the assay of lipoprotein lipase, using a stable, radioactive substrate emulsion. Fatty acid-labeled trioleoylglycerol was emulsified by homogenization in glycerol with lecithin as detergent. This anhydrous emulsion was stable for at least six weeks. Substrate solutions for enzyme assay were prepared by diluting the emulsion with buffer containing serum and albumin. The fatty acid produced on hydrolysis was isolated in a one-step liquid-liquid partition system. Incubations with extracts of acetone powders from adipose tissue displayed characteristics of lipoprotein lipase activity, i.e., serum dependence and inhibition by NaCl and protamine. The method is rapid (less than 1 hour), sensitive and reproducible, and suitable for routine use.", "contents": "A stable, radioactive substrate emulsion for assay of lipoprotein lipase. A method is described for the assay of lipoprotein lipase, using a stable, radioactive substrate emulsion. Fatty acid-labeled trioleoylglycerol was emulsified by homogenization in glycerol with lecithin as detergent. This anhydrous emulsion was stable for at least six weeks. Substrate solutions for enzyme assay were prepared by diluting the emulsion with buffer containing serum and albumin. The fatty acid produced on hydrolysis was isolated in a one-step liquid-liquid partition system. Incubations with extracts of acetone powders from adipose tissue displayed characteristics of lipoprotein lipase activity, i.e., serum dependence and inhibition by NaCl and protamine. The method is rapid (less than 1 hour), sensitive and reproducible, and suitable for routine use."}
{"id": "PMID:9466", "title": "A new method for the determination of gamma-glutamyltransferase in serum.", "content": "A new, simple and sensitive method is described for assay of serum gamma-glutamyltransferase activity based on the hydrolysis of the substrate L-gamma-glutamyl-3-carboxy-4-nitranilide which offers the advantage of producing directly its own chromogen. The substrate is highly soluble and the method can therefore easily be adapted to any equipment for the automated assay of gamma-glutamyltransferase. The activities at measured optimum substrate concentration are slightly higher than with the Szasz ((1969), Clin. Chem. 15, 124-136) method in which L-glutamyl-p-nitroanilide is used as substrate.", "contents": "A new method for the determination of gamma-glutamyltransferase in serum. A new, simple and sensitive method is described for assay of serum gamma-glutamyltransferase activity based on the hydrolysis of the substrate L-gamma-glutamyl-3-carboxy-4-nitranilide which offers the advantage of producing directly its own chromogen. The substrate is highly soluble and the method can therefore easily be adapted to any equipment for the automated assay of gamma-glutamyltransferase. The activities at measured optimum substrate concentration are slightly higher than with the Szasz ((1969), Clin. Chem. 15, 124-136) method in which L-glutamyl-p-nitroanilide is used as substrate."}
{"id": "PMID:9467", "title": "A reversible, hydrogen ion blockade of spontaneous oocyte maturation in the starfish: locus of action.", "content": "Starfish (Asterias forbesi) oocytes encased within their follicle cells mature spontaneously during a portion of the normal reproductive period when released from the ovary into seawater. A previous report has shown that oocytes isolated in acidic seawater do not mature spontaneously but retain the capacity to do so when returned to normal seawater. The object of this study was to determine the mechanism by which acidic pH reversibly blocks spontaneous oocyte maturation in isolated follicles. Incidence of spontaneous oocyte maturation in follicles isolated in acidic seawater decreased as pH decreased from 7 to 4. Oocytes in which spontaneous maturation was inhibited (ASW at pH 4.7 TO 5.4) underwent germinal vesicle breakdown with the addition of 1-methyladenine. Oocytes isolated in acidic seawater (pH 4 or 5) with intact follicle cells matured spontaneously when transferred immediately to normal seawater pH 8); after four hours, 60-65% of the follicles incubated in seawater at pH 5 matured spontaneously when returned to normal seawater as compared to less than 10% of the follicles maintained at pH 4. Inhibition of spontaneous maturation was not reversible in the absence of the follicle cells. Oocytes isolated in acidic seawater with their follicle cells did not spontaneously mature when transferred to calcium-free seawater at pH 8. The results obtained support the hypothesis that acidic seawater reversibly inhibits spontaneous oocyte maturation by interfering with the release of meiosis-inducing substance from the follicle cells.", "contents": "A reversible, hydrogen ion blockade of spontaneous oocyte maturation in the starfish: locus of action. Starfish (Asterias forbesi) oocytes encased within their follicle cells mature spontaneously during a portion of the normal reproductive period when released from the ovary into seawater. A previous report has shown that oocytes isolated in acidic seawater do not mature spontaneously but retain the capacity to do so when returned to normal seawater. The object of this study was to determine the mechanism by which acidic pH reversibly blocks spontaneous oocyte maturation in isolated follicles. Incidence of spontaneous oocyte maturation in follicles isolated in acidic seawater decreased as pH decreased from 7 to 4. Oocytes in which spontaneous maturation was inhibited (ASW at pH 4.7 TO 5.4) underwent germinal vesicle breakdown with the addition of 1-methyladenine. Oocytes isolated in acidic seawater (pH 4 or 5) with intact follicle cells matured spontaneously when transferred immediately to normal seawater pH 8); after four hours, 60-65% of the follicles incubated in seawater at pH 5 matured spontaneously when returned to normal seawater as compared to less than 10% of the follicles maintained at pH 4. Inhibition of spontaneous maturation was not reversible in the absence of the follicle cells. Oocytes isolated in acidic seawater with their follicle cells did not spontaneously mature when transferred to calcium-free seawater at pH 8. The results obtained support the hypothesis that acidic seawater reversibly inhibits spontaneous oocyte maturation by interfering with the release of meiosis-inducing substance from the follicle cells."}
{"id": "PMID:9468", "title": "Production of retarded, albino, regenerates in newts by alpha-methyl-p-tyrosine.", "content": "Inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine retarded growth and prevented melanization of limb regenerate in adult newts (Triturus cristatus).", "contents": "Production of retarded, albino, regenerates in newts by alpha-methyl-p-tyrosine. Inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine retarded growth and prevented melanization of limb regenerate in adult newts (Triturus cristatus)."}
{"id": "PMID:9470", "title": "On Ho's \"modern logic and schizophrenic thinking\".", "content": "The purpose of this note is to point out that conclusions drawn in the title paper about the role of logic in the schizophrenia thought process are not reliable, since they are based on patients medicated with antipsychotic drugs. The substance of this note is drawn from the title paper and related literature. The principal conclusion is that Dr. Ho's deductions about the role of logic in schizophrenia follow only if one confuses psychiatric diagnosis with psychotic behavior.", "contents": "On Ho's \"modern logic and schizophrenic thinking\". The purpose of this note is to point out that conclusions drawn in the title paper about the role of logic in the schizophrenia thought process are not reliable, since they are based on patients medicated with antipsychotic drugs. The substance of this note is drawn from the title paper and related literature. The principal conclusion is that Dr. Ho's deductions about the role of logic in schizophrenia follow only if one confuses psychiatric diagnosis with psychotic behavior."}
{"id": "PMID:9471", "title": "Medication, logic, and schizophernic thinking: a reply to Marini.", "content": "This article attempts to answer Marini's critique of my paper and to clarify the issue of medication in the study of the role of logic in the production of schizophrenic thought. It is argued that clinical observations do not lead one to believe that either the form or the content of schizophrenic thought disorder changes in any fundamental way as a result of medication. Consequently, the fact that most of the schizophrenic Ss were medicated at the time of the original research does not negate the conclusion that the thinking pathology found in schizophrenics cannot be accounted for by positing a basic defect in their deductive reasoning process.", "contents": "Medication, logic, and schizophernic thinking: a reply to Marini. This article attempts to answer Marini's critique of my paper and to clarify the issue of medication in the study of the role of logic in the production of schizophrenic thought. It is argued that clinical observations do not lead one to believe that either the form or the content of schizophrenic thought disorder changes in any fundamental way as a result of medication. Consequently, the fact that most of the schizophrenic Ss were medicated at the time of the original research does not negate the conclusion that the thinking pathology found in schizophrenics cannot be accounted for by positing a basic defect in their deductive reasoning process."}
{"id": "PMID:9491", "title": "Analysis of passive and active electrophysiologic properties of neurons in mammalian nodose ganglia maintained in vitro.", "content": "1. We studied the passive and active electrical properties of the soma membrane of neurons in nodose ganglia removed from cats and rabbits and maintained in vitro. The ganglia were superfused at 37 degrees C with a solution formulated to approximate the extracellular fluid of each species. The solution was buffered to pH 7.34, continuously equilibrated with 95% O2 and 5% CO2, and contained dialyzed calf serum and glucose. We also examined these properties in nodose ganglion neurons in vivo. Intracellular recordings were obtained with glass micropipettes filled with either 3 M KCl or 5 M K acetate. 2. We determined mean values for a variety of passive and active electrophysiologic properties. Values obtained in vitro did not differ significantly from those obtained in vivo. Based on the passive electrical properties of the soma membrane, neurons in the nodose ganglion appear to be a uniform population, despite the different sensory modalities conveyed by the afferent fibers. 3. Cell bodies of neurons generated action potentials in response to impulses in their afferent fibers. Somatic spikes could be evoked by stimulation of either the supranodose or infranodose vagus nerve, and an inflection point could be seen on their rising phase. When the vagus nerve was stimulated at frequencies greater than 10-20 Hz, the generation of somatic spikes often became progressively delayed and then failed completely, leaving a smaller potential (IS spike) which was apparently generated in the initial complex. The afterhyperpolarization was associated only with the somatic spike. 4. Many neurons, both in vitro and in vivo, developed a persistent hyperpolarization when repetitive action potentials occurred in the soma. This hyperpolarization was apparent at frequencies as low as 1-2 Hz, persisted for up to 5 s after the occurrence of the last somatic spike, and sometimes caused failure of somatic spikes to be generated. 5. Neurons in both species differed in their responses to suprathreshold depolarization applied through the recording electrode. Some neurons produced a train of action potentials which lasted for the duration of the depolarizing pulse, the frequency of the train being related to the magnitude of depolarization. The trains were characterized by gradually decreasing spike amplitudes and increasing interspike intervals. Other neurons responded with only a single spike or brief burst of action potentials at the beginning of depolarization to threshold. 6. It is suggested that the adaptive properties of the soma membrane of a peripheral sensory neuron are similar to those of its sensory ending, and that electrophysiological studies of the soma membrane may provide an opportunity to examine mechanisms of receptor adaptation.", "contents": "Analysis of passive and active electrophysiologic properties of neurons in mammalian nodose ganglia maintained in vitro. 1. We studied the passive and active electrical properties of the soma membrane of neurons in nodose ganglia removed from cats and rabbits and maintained in vitro. The ganglia were superfused at 37 degrees C with a solution formulated to approximate the extracellular fluid of each species. The solution was buffered to pH 7.34, continuously equilibrated with 95% O2 and 5% CO2, and contained dialyzed calf serum and glucose. We also examined these properties in nodose ganglion neurons in vivo. Intracellular recordings were obtained with glass micropipettes filled with either 3 M KCl or 5 M K acetate. 2. We determined mean values for a variety of passive and active electrophysiologic properties. Values obtained in vitro did not differ significantly from those obtained in vivo. Based on the passive electrical properties of the soma membrane, neurons in the nodose ganglion appear to be a uniform population, despite the different sensory modalities conveyed by the afferent fibers. 3. Cell bodies of neurons generated action potentials in response to impulses in their afferent fibers. Somatic spikes could be evoked by stimulation of either the supranodose or infranodose vagus nerve, and an inflection point could be seen on their rising phase. When the vagus nerve was stimulated at frequencies greater than 10-20 Hz, the generation of somatic spikes often became progressively delayed and then failed completely, leaving a smaller potential (IS spike) which was apparently generated in the initial complex. The afterhyperpolarization was associated only with the somatic spike. 4. Many neurons, both in vitro and in vivo, developed a persistent hyperpolarization when repetitive action potentials occurred in the soma. This hyperpolarization was apparent at frequencies as low as 1-2 Hz, persisted for up to 5 s after the occurrence of the last somatic spike, and sometimes caused failure of somatic spikes to be generated. 5. Neurons in both species differed in their responses to suprathreshold depolarization applied through the recording electrode. Some neurons produced a train of action potentials which lasted for the duration of the depolarizing pulse, the frequency of the train being related to the magnitude of depolarization. The trains were characterized by gradually decreasing spike amplitudes and increasing interspike intervals. Other neurons responded with only a single spike or brief burst of action potentials at the beginning of depolarization to threshold. 6. It is suggested that the adaptive properties of the soma membrane of a peripheral sensory neuron are similar to those of its sensory ending, and that electrophysiological studies of the soma membrane may provide an opportunity to examine mechanisms of receptor adaptation."}
{"id": "PMID:9493", "title": "Influence of molasses lignin-hemicellulose fractions in rat nutrition.", "content": "Previous reports have shown that fractionation of the non-sugar, non-dialyzable components of cane molasses yielded a fraction designated as a black phenolic-carbohydrate complex. Incorporation of 0.03% of this complex into diets fed weanling male rats significantly increased the growth rate above that of rats fed the basal diet alone. This study was conducted to determine the chemical nature and growth stimulating action of the black phenol-carbohydrate complex. Alkaline cleavage under nitrogen yielded a mixture of phenols and a carbohydrate fraction which was recovered by precipitation at pH 6 in four volumes of ethanol. The alkaline cleaved, free hemicellulose was non-diayzable and stimulated growth when incorporated into rat diets at the 0.03% levels. Acid hydrolysis of the complex yielded an insoluble product identified as lignin and found to represent 18% to 20% of the entire complex. The chemical nature of this ligninhemicellulose fraction and the previously reported growth-enhancing acid resistant hemicellulose fraction isolated from various plant sources were found to be similar.", "contents": "Influence of molasses lignin-hemicellulose fractions in rat nutrition. Previous reports have shown that fractionation of the non-sugar, non-dialyzable components of cane molasses yielded a fraction designated as a black phenolic-carbohydrate complex. Incorporation of 0.03% of this complex into diets fed weanling male rats significantly increased the growth rate above that of rats fed the basal diet alone. This study was conducted to determine the chemical nature and growth stimulating action of the black phenol-carbohydrate complex. Alkaline cleavage under nitrogen yielded a mixture of phenols and a carbohydrate fraction which was recovered by precipitation at pH 6 in four volumes of ethanol. The alkaline cleaved, free hemicellulose was non-diayzable and stimulated growth when incorporated into rat diets at the 0.03% levels. Acid hydrolysis of the complex yielded an insoluble product identified as lignin and found to represent 18% to 20% of the entire complex. The chemical nature of this ligninhemicellulose fraction and the previously reported growth-enhancing acid resistant hemicellulose fraction isolated from various plant sources were found to be similar."}
{"id": "PMID:9494", "title": "Effects of alkali-treated proteins: feeding studies with free and protein-bound lysinoalanine in rats and other animals.", "content": "To find out whether alkali-treated proteins posses nephrotoxic properties, feeding studies were conducted with drastically treated soybean protein and casein, and also with lysinoalanine (LAL), the amino acid known to be formed in protein subjected to high pH at elevated temperature. The feeding of synthesized LAL to rats at dietary levels of 100 ppm and above induced typical renal changes, called nephrocytomegalia. No such changes or any other indications of toxicity were observed, however, upon feeding much higher levels of LAL (up to 6,000 ppm) when provided as the protein-bound compound in alkali-treated casein or soybean protein. When set free by complete acid hydrolysis, LAL induced considerable renal activity, comparable to that of the synthetic compound. These results indicate that alkali treatment of proteins does not induce nephrotoxic properties provided that the compound remains protein-bound. Some nephrotoxic activity was observed, however, with peptide-boound LAL in break-down products (molecular weight less than 5,000) of alkali-treated casein, but considerably less than that of the free compound. LAL-analyses in blood, urine, and feces of rats fed free or protein-bound LAL indicated a positive correlation between intestinal absorption and nephrotoxic potential. No renal changes were encountered upon feeding diets with 1,000 ppm synthetic LAL to mice, hamsters, rabbits, quail, dogs or monkeys, which suggest a species specificity of LAL-induced renal changes in rats.", "contents": "Effects of alkali-treated proteins: feeding studies with free and protein-bound lysinoalanine in rats and other animals. To find out whether alkali-treated proteins posses nephrotoxic properties, feeding studies were conducted with drastically treated soybean protein and casein, and also with lysinoalanine (LAL), the amino acid known to be formed in protein subjected to high pH at elevated temperature. The feeding of synthesized LAL to rats at dietary levels of 100 ppm and above induced typical renal changes, called nephrocytomegalia. No such changes or any other indications of toxicity were observed, however, upon feeding much higher levels of LAL (up to 6,000 ppm) when provided as the protein-bound compound in alkali-treated casein or soybean protein. When set free by complete acid hydrolysis, LAL induced considerable renal activity, comparable to that of the synthetic compound. These results indicate that alkali treatment of proteins does not induce nephrotoxic properties provided that the compound remains protein-bound. Some nephrotoxic activity was observed, however, with peptide-boound LAL in break-down products (molecular weight less than 5,000) of alkali-treated casein, but considerably less than that of the free compound. LAL-analyses in blood, urine, and feces of rats fed free or protein-bound LAL indicated a positive correlation between intestinal absorption and nephrotoxic potential. No renal changes were encountered upon feeding diets with 1,000 ppm synthetic LAL to mice, hamsters, rabbits, quail, dogs or monkeys, which suggest a species specificity of LAL-induced renal changes in rats."}
{"id": "PMID:9495", "title": "Effects of divalent cations on vitamin B12 adsorption to brush borders of rat intestine.", "content": "A brush border preparation from rat intestine was incubated with rat intrinsic factor-vitamin B12 complex in 0.01 M Tris-HCl buffer, pH 7.4. The 57Co-B12 uptake to brush borders was proportional to the amount of protein or to alkaline phosphatase activity in the preparations. The uptake increased with time of incubation. At 37degreesC, the uptake after incubation for 15 min was 80-85% of that for one hr. The uptake at 4degreesC was approximately 70% of that at 37degreesC. Ther was no difference as a result of adding glucose to the incubation medium. The uptake was observed in the alkaline environment above pH 6.3. Maximum uptake occurred at pH 8.0. Brush borders washed with Krebs-Ringer bicarbonate buffer (pH 7.4) exhibited no difference in B12 uptake, whether in the presence or absence of calcium ion. But brush borders washed with ethylenediaminetetraacetate exhibited no uptake when incubated in calcium-free medium. The uptake reached a maximum by addition of calcium ion at a concentration of 0.3 mM, and was not alter up to 10 mM. Addition of magnesium ion exhibited no uptake. Calcium-dependent B12 uptake was markedly inhibited by manganese ion. Magnesium ion seemed to slightly inhibit the calcium-dependent uptake.", "contents": "Effects of divalent cations on vitamin B12 adsorption to brush borders of rat intestine. A brush border preparation from rat intestine was incubated with rat intrinsic factor-vitamin B12 complex in 0.01 M Tris-HCl buffer, pH 7.4. The 57Co-B12 uptake to brush borders was proportional to the amount of protein or to alkaline phosphatase activity in the preparations. The uptake increased with time of incubation. At 37degreesC, the uptake after incubation for 15 min was 80-85% of that for one hr. The uptake at 4degreesC was approximately 70% of that at 37degreesC. Ther was no difference as a result of adding glucose to the incubation medium. The uptake was observed in the alkaline environment above pH 6.3. Maximum uptake occurred at pH 8.0. Brush borders washed with Krebs-Ringer bicarbonate buffer (pH 7.4) exhibited no difference in B12 uptake, whether in the presence or absence of calcium ion. But brush borders washed with ethylenediaminetetraacetate exhibited no uptake when incubated in calcium-free medium. The uptake reached a maximum by addition of calcium ion at a concentration of 0.3 mM, and was not alter up to 10 mM. Addition of magnesium ion exhibited no uptake. Calcium-dependent B12 uptake was markedly inhibited by manganese ion. Magnesium ion seemed to slightly inhibit the calcium-dependent uptake."}
{"id": "PMID:9496", "title": "Purification and properties of the dihydrofolate synthetase from Serratia indica.", "content": "The dihydrofolate synthetase (EC 6.3.2.12) responsible for catalyzing the synthesis of dihydrofolic acid from dihydropteroic acid and L-glutamic acid was purified about 130-fold from extracts of Serratia indica IFO 3759 by ammonium sulfate fractionation, DEAE-Sephadex column chromatography, Sephadex G-200 gel filtration, and DEAE-cellulose column chromatography. The enzyme preparation obtained was shown to be homogeneous by DEAE-cellulose column chromatography and ultracentrifugal analysis. The sedimentation coefficient of this enzyme was 3.9 S, and the molecular weight was determined to be about 47,000 by Sephadex G-100. The optimum pH for the reaction was 9.0. The enzymatic reaction required dihydropteroate, L-glutamate and ATP as substrates, and Mg2+ and K+ as cofactors. gamma-L-Glutamyl-L-glutamic acid cannot replace L-glutamic acid as the substrate. Neither pteroic acid nor tetrahydropteroic acid can be used as the substrate. ATP was partially replaced by ITP or GTP. The enzyme reaction was inhibited by the addition of AD, but not by AMP. One mole of dihydrofolate, 1 mole of ADP and 1 mole of orthophosphate were produced from each 1 mole of dihydropteroic acid, L-glutamic acid, and ATP by the following equation: 7,8-Dihydropteroic acid ml-Glutamic acid matp Mg2+, K+ leads to Dihydrofolic acid + ADP + Pi. These results suggest that the systematic name for the dihydrofolate synthetase is 7,8-dihydropteroate: L-glutamate ligase (ADP).", "contents": "Purification and properties of the dihydrofolate synthetase from Serratia indica. The dihydrofolate synthetase (EC 6.3.2.12) responsible for catalyzing the synthesis of dihydrofolic acid from dihydropteroic acid and L-glutamic acid was purified about 130-fold from extracts of Serratia indica IFO 3759 by ammonium sulfate fractionation, DEAE-Sephadex column chromatography, Sephadex G-200 gel filtration, and DEAE-cellulose column chromatography. The enzyme preparation obtained was shown to be homogeneous by DEAE-cellulose column chromatography and ultracentrifugal analysis. The sedimentation coefficient of this enzyme was 3.9 S, and the molecular weight was determined to be about 47,000 by Sephadex G-100. The optimum pH for the reaction was 9.0. The enzymatic reaction required dihydropteroate, L-glutamate and ATP as substrates, and Mg2+ and K+ as cofactors. gamma-L-Glutamyl-L-glutamic acid cannot replace L-glutamic acid as the substrate. Neither pteroic acid nor tetrahydropteroic acid can be used as the substrate. ATP was partially replaced by ITP or GTP. The enzyme reaction was inhibited by the addition of AD, but not by AMP. One mole of dihydrofolate, 1 mole of ADP and 1 mole of orthophosphate were produced from each 1 mole of dihydropteroic acid, L-glutamic acid, and ATP by the following equation: 7,8-Dihydropteroic acid ml-Glutamic acid matp Mg2+, K+ leads to Dihydrofolic acid + ADP + Pi. These results suggest that the systematic name for the dihydrofolate synthetase is 7,8-dihydropteroate: L-glutamate ligase (ADP)."}
{"id": "PMID:9498", "title": "The use of microsurgery in the treatment of the undescended testis.", "content": "An experimental method of orchidopexy for high inguinal or abdominal testes, in the dog, using microsurgical anastomosis of the testicular vessels to vessels of the thigh or inferior epigastric vessels, is described. Experimental results suggest that this is a feasible method of treatment of such testes. A clinical trial of the method has commenced.", "contents": "The use of microsurgery in the treatment of the undescended testis. An experimental method of orchidopexy for high inguinal or abdominal testes, in the dog, using microsurgical anastomosis of the testicular vessels to vessels of the thigh or inferior epigastric vessels, is described. Experimental results suggest that this is a feasible method of treatment of such testes. A clinical trial of the method has commenced."}
{"id": "PMID:9499", "title": "The significance of the time interval in twin delivery.", "content": "In order to evaluate the influence of the time interval on the second twin in twin deliveries, we have used more precise criteria than have been used in the literature to date. In the period from July 1, 1970 to December 31, 1974, 35 twin deliveries in our hospital were analyzed, in which both twins fulfilled the following criteria: 1. vertex presentation 2. vaginal deliveries 3. birth weight above 2000 g. We analyzed various parameters in the clinical and acidity score of the second twin alone as well as in comparison to the first twin. The following points of view were considered: 1. The more sensitive aspect of morbidity was utilized by including the assessment of the state of the newborn rather than just mortality. 2. Since Caesarean sections in twins are often performed for a fetal indication, short time intervals between the birth of both infants correlate intrinsically with a higher risk for the second twin. Therefore we considered only vaginal deliveries in order to exclude this intrinsic correlation. 3. By excluding infants below a birth weight of 2000 g, the influence of the low birth weight of the second twin was eliminated. 4. The frequently occurring positional anomalies of the second twin will deteriorate the conditions independent of the time interval. therefore we have considered only births from vertex presentations. A comparison of the acidity state demonstrated that the actual pH values in the umbilical artery blood of these second twins (Fig. 1) decrease statistically significantly with increasing time intervals. this is also true for metabolic acidity (pHqu40). The differences of the actual pH values (Fig. 2) and the pHqu40 values between the first and second twin decreases significantly also with an increasing time interval. Our results indicate that obstetricians, according to the clinical conditions, should accomplish the birth of the second twin as soon as possible after the birth of the first twin.", "contents": "The significance of the time interval in twin delivery. In order to evaluate the influence of the time interval on the second twin in twin deliveries, we have used more precise criteria than have been used in the literature to date. In the period from July 1, 1970 to December 31, 1974, 35 twin deliveries in our hospital were analyzed, in which both twins fulfilled the following criteria: 1. vertex presentation 2. vaginal deliveries 3. birth weight above 2000 g. We analyzed various parameters in the clinical and acidity score of the second twin alone as well as in comparison to the first twin. The following points of view were considered: 1. The more sensitive aspect of morbidity was utilized by including the assessment of the state of the newborn rather than just mortality. 2. Since Caesarean sections in twins are often performed for a fetal indication, short time intervals between the birth of both infants correlate intrinsically with a higher risk for the second twin. Therefore we considered only vaginal deliveries in order to exclude this intrinsic correlation. 3. By excluding infants below a birth weight of 2000 g, the influence of the low birth weight of the second twin was eliminated. 4. The frequently occurring positional anomalies of the second twin will deteriorate the conditions independent of the time interval. therefore we have considered only births from vertex presentations. A comparison of the acidity state demonstrated that the actual pH values in the umbilical artery blood of these second twins (Fig. 1) decrease statistically significantly with increasing time intervals. this is also true for metabolic acidity (pHqu40). The differences of the actual pH values (Fig. 2) and the pHqu40 values between the first and second twin decreases significantly also with an increasing time interval. Our results indicate that obstetricians, according to the clinical conditions, should accomplish the birth of the second twin as soon as possible after the birth of the first twin."}
{"id": "PMID:9500", "title": "Evaluation of the fetal state by automatic analysis of the heart rate. 2. Deceleration areas and umbilical artery blood pH.", "content": "Fetal heart rate (FHR) deceleration areas were studied to obtain by objective measurement of the FHR, their prognostic value of the new-born state. 1. There is a reasonably good correlation between FHR deceleration areas and UApH (Tab. II). Such a correlation was found by SHELLEY and TIPTON [6] for the whole deceleration area, and by TOURNAIRE et al. [10] for areas divided in a slightly different way. The correlation coefficients between FHR deceleration areas and Apgar score at 1 minute are within a close range of those of the FHR deceleration area and UApH (Tab. I and II). 2. According to the time relationship between deceleration areas and uterine contractions the best correlation coefficient was obtained surprisingly for total, followed by residual and then simultaneous areas. These results agree with those of SHELLEY and TIPTON [6] suggesting that in practice a simple measurement of the whole deceleration area, regardless of the uterine contractions is a sufficient method in evaluating FHR patterns. 3. The special purpose computer built by the BAUDELOCQUE research group can be used on-line, thus in clinical practice. It was not the case for the manual method [4] or the method using a large programmed computer [10]. 4 The evaluation of deceleration areas appears to have several advantages: 1. It provides objective measurements. 2. The unit used is independant of factors such as display speed or scale of the strip-chart. 3. The data is reduced: A few numbers replace the long descriptions of the usual clinical classifications.", "contents": "Evaluation of the fetal state by automatic analysis of the heart rate. 2. Deceleration areas and umbilical artery blood pH. Fetal heart rate (FHR) deceleration areas were studied to obtain by objective measurement of the FHR, their prognostic value of the new-born state. 1. There is a reasonably good correlation between FHR deceleration areas and UApH (Tab. II). Such a correlation was found by SHELLEY and TIPTON [6] for the whole deceleration area, and by TOURNAIRE et al. [10] for areas divided in a slightly different way. The correlation coefficients between FHR deceleration areas and Apgar score at 1 minute are within a close range of those of the FHR deceleration area and UApH (Tab. I and II). 2. According to the time relationship between deceleration areas and uterine contractions the best correlation coefficient was obtained surprisingly for total, followed by residual and then simultaneous areas. These results agree with those of SHELLEY and TIPTON [6] suggesting that in practice a simple measurement of the whole deceleration area, regardless of the uterine contractions is a sufficient method in evaluating FHR patterns. 3. The special purpose computer built by the BAUDELOCQUE research group can be used on-line, thus in clinical practice. It was not the case for the manual method [4] or the method using a large programmed computer [10]. 4 The evaluation of deceleration areas appears to have several advantages: 1. It provides objective measurements. 2. The unit used is independant of factors such as display speed or scale of the strip-chart. 3. The data is reduced: A few numbers replace the long descriptions of the usual clinical classifications."}
{"id": "PMID:9503", "title": "Dc Polarographic assay of tetracyclines.", "content": "The inhibitory effect of dioctyl sodium sulfosuccinate on hog pepsin activity was investigated over the pH 1.5-3.0 range. The inhibitory effect was studied using a natural substrate, hemoglobin, and a synthetic substrate, N-acetyl-L-diiodotyrosine. The mechanistic studies revealed that a substrate-inhibitor interaction was the major mechanism of inhibition with hemoglobin. However, some direct enzyme inhibition also was involved. With the synthetic substrate, the inhibition las due to a competition between the substrate and the inhibitor molecules for the enzyme. The possible therapeutic significance of the inhibitory effect of the medicinal surfactant is discussed.", "contents": "Dc Polarographic assay of tetracyclines. The inhibitory effect of dioctyl sodium sulfosuccinate on hog pepsin activity was investigated over the pH 1.5-3.0 range. The inhibitory effect was studied using a natural substrate, hemoglobin, and a synthetic substrate, N-acetyl-L-diiodotyrosine. The mechanistic studies revealed that a substrate-inhibitor interaction was the major mechanism of inhibition with hemoglobin. However, some direct enzyme inhibition also was involved. With the synthetic substrate, the inhibition las due to a competition between the substrate and the inhibitor molecules for the enzyme. The possible therapeutic significance of the inhibitory effect of the medicinal surfactant is discussed."}
{"id": "PMID:9504", "title": "Isolation and characterization of the cardiotonic polypeptide anthopleurin-A from the sea anemone Anthopleura xanthogrammica.", "content": "A highly potent cardiotonic polypeptide, anthopleurin-A, was isolated from the sea anemone, Anthopleura xanthogrammica (Brandt), using solvent partition, gel permeation chromatography, and cation-exchange chromatography. It is a pure basic polypeptide wtih a molecular weight of about 5500.", "contents": "Isolation and characterization of the cardiotonic polypeptide anthopleurin-A from the sea anemone Anthopleura xanthogrammica. A highly potent cardiotonic polypeptide, anthopleurin-A, was isolated from the sea anemone, Anthopleura xanthogrammica (Brandt), using solvent partition, gel permeation chromatography, and cation-exchange chromatography. It is a pure basic polypeptide wtih a molecular weight of about 5500."}
{"id": "PMID:9505", "title": "Solid-state anomalies in IR spectra of compounds of pharmaceutical interest.", "content": "Solid-state anomalies in the IR spectra of lysine monohydrochloride, etoxadrol hydrochloride, thiamine hydrochloride, and L-histidine in a potassium bromide matrix were noted. With the first three compounds, the anomalies were due to metathetical exchange of the halide anion between the compound and the matrix. The anomaly seen with L-histidine was related to the crystal structure.", "contents": "Solid-state anomalies in IR spectra of compounds of pharmaceutical interest. Solid-state anomalies in the IR spectra of lysine monohydrochloride, etoxadrol hydrochloride, thiamine hydrochloride, and L-histidine in a potassium bromide matrix were noted. With the first three compounds, the anomalies were due to metathetical exchange of the halide anion between the compound and the matrix. The anomaly seen with L-histidine was related to the crystal structure."}
{"id": "PMID:9509", "title": "Calcium-binding protein in bull seminal vesicle secretion and seminal plasma.", "content": "A protein which showed high affinity for calcium ions was isolated from bull seminal vesicle secretion and seminal plasma. Its calcium-binding activity depended on the ionic strength and pH of the medium. The dissociation constant was 7-7 X 10(-7) M and there were 14 binding sites per protein molecule. The molecular weight of calcium-binding protein from bull seminal vesicle secretion, estimated by the gel filtration method, was 110,000. The protein may be involved in the regulation of the calcium ion level in seminal plasma.", "contents": "Calcium-binding protein in bull seminal vesicle secretion and seminal plasma. A protein which showed high affinity for calcium ions was isolated from bull seminal vesicle secretion and seminal plasma. Its calcium-binding activity depended on the ionic strength and pH of the medium. The dissociation constant was 7-7 X 10(-7) M and there were 14 binding sites per protein molecule. The molecular weight of calcium-binding protein from bull seminal vesicle secretion, estimated by the gel filtration method, was 110,000. The protein may be involved in the regulation of the calcium ion level in seminal plasma."}
{"id": "PMID:9510", "title": "Clonidine and related analogues. Quantitative correlations.", "content": "Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the critical role of the steric effect in the ortho positions. On the other hand, attempted quantitative correlations between physicochemical parameters and central hypotensive activity were unsuccessful. These results are discussed in the light of the postulated mechanism of action of clonidine.", "contents": "Clonidine and related analogues. Quantitative correlations. Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the critical role of the steric effect in the ortho positions. On the other hand, attempted quantitative correlations between physicochemical parameters and central hypotensive activity were unsuccessful. These results are discussed in the light of the postulated mechanism of action of clonidine."}
{"id": "PMID:9511", "title": "Synthesis and pharmacology of novel anxiolytic agents derived from 2-[(dialkylamino)methyl-4H-triazol-4-yl] benzophenones and related heterocyclic benzophenones.", "content": "A series of novel [(dialkylamino)methyl-4H-1,2,4-triazol-4-yl]benzophenones and related compounds has been prepared via total synthesis from substituted aminodiphenylmethanes or by hydrolysis and subsequent methylation of triazolobenzodiazepines. These new triazole compounds were found to have potent sedative and muscle relaxing activity in mice (i.e., these compounds depressed the traction and dish reflexes). In addition, the title compounds antagonized the clonic convulsions induced in mice by the administration of pentylenetratrazole (Metrazol, 85 mg/kg), with ED50's varying from 2.0 to 23.0 mg/kg, and the lethality induced by thiosemicarbazide, with ED50's varying from 0.02 to 9.0 mg/kg. In several biological tests, the potency of seven new benzophenone derivatives approached or exceed that of diazepam (35a) or its glycylaminobenzophenone analogue 36.", "contents": "Synthesis and pharmacology of novel anxiolytic agents derived from 2-[(dialkylamino)methyl-4H-triazol-4-yl] benzophenones and related heterocyclic benzophenones. A series of novel [(dialkylamino)methyl-4H-1,2,4-triazol-4-yl]benzophenones and related compounds has been prepared via total synthesis from substituted aminodiphenylmethanes or by hydrolysis and subsequent methylation of triazolobenzodiazepines. These new triazole compounds were found to have potent sedative and muscle relaxing activity in mice (i.e., these compounds depressed the traction and dish reflexes). In addition, the title compounds antagonized the clonic convulsions induced in mice by the administration of pentylenetratrazole (Metrazol, 85 mg/kg), with ED50's varying from 2.0 to 23.0 mg/kg, and the lethality induced by thiosemicarbazide, with ED50's varying from 0.02 to 9.0 mg/kg. In several biological tests, the potency of seven new benzophenone derivatives approached or exceed that of diazepam (35a) or its glycylaminobenzophenone analogue 36."}
{"id": "PMID:9512", "title": "Na+ transport by rabbit urinary bladder, a tight epithelium.", "content": "By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially when the animal is Na+-depleted.", "contents": "Na+ transport by rabbit urinary bladder, a tight epithelium. By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially when the animal is Na+-depleted."}
{"id": "PMID:9513", "title": "Perturbational effects of inorganic cations on human erythrocyte membranes.", "content": "The perturbational effects of monovalent and divalent cations on human erythrocyte membranes were analyzed by examining their influence on kinetic and structural characteristics of trinitrobenzenesulfonic acid (TNBS) incorporation into the amino groups of protein and phospholipid structural components. The stimulatory effects of monovalent cations on TNBS incorporation, which were size-independent and attributed to nonspecific membrane alterations resulting from ionic strength factors, contrasted with the more pronounced stimulatory properties of divalent cations which were markedly size-dependent. These stimulatory effects of cations on TNBS incorporation were associated with alterations not only in rate but also in activation energy in incorporation. Changes in activation energy produced by divalent cations paralleled their ability to perturb membrane protein components and probably reflected changes in probe permeation. The rate of TNBS incorporation exhibited a dependence on divalent cation ionic radius which paralleled ion-induced perturbations in the labelling of the membrane amino phospholipid phosphatidylethanolamine. Divalent cations differed both in the relative extent and in the characteristics of protein and phospholipid perturbation. Alkaline earth cations behaved as a rather homogeneous group while Ni++, Co++ and Mn++ constituted a second heterogeneous group. The influence of monovalent and divalent cations on the hemolytic behavior of intact erythrocytes paralleled their effects on TNBS incorporation into isolated membranes rather closely. It is suggested that TNBS incorporation may provide a valuable means of analyzing functionally relevant cation-induced alterations in biological membranes in general.", "contents": "Perturbational effects of inorganic cations on human erythrocyte membranes. The perturbational effects of monovalent and divalent cations on human erythrocyte membranes were analyzed by examining their influence on kinetic and structural characteristics of trinitrobenzenesulfonic acid (TNBS) incorporation into the amino groups of protein and phospholipid structural components. The stimulatory effects of monovalent cations on TNBS incorporation, which were size-independent and attributed to nonspecific membrane alterations resulting from ionic strength factors, contrasted with the more pronounced stimulatory properties of divalent cations which were markedly size-dependent. These stimulatory effects of cations on TNBS incorporation were associated with alterations not only in rate but also in activation energy in incorporation. Changes in activation energy produced by divalent cations paralleled their ability to perturb membrane protein components and probably reflected changes in probe permeation. The rate of TNBS incorporation exhibited a dependence on divalent cation ionic radius which paralleled ion-induced perturbations in the labelling of the membrane amino phospholipid phosphatidylethanolamine. Divalent cations differed both in the relative extent and in the characteristics of protein and phospholipid perturbation. Alkaline earth cations behaved as a rather homogeneous group while Ni++, Co++ and Mn++ constituted a second heterogeneous group. The influence of monovalent and divalent cations on the hemolytic behavior of intact erythrocytes paralleled their effects on TNBS incorporation into isolated membranes rather closely. It is suggested that TNBS incorporation may provide a valuable means of analyzing functionally relevant cation-induced alterations in biological membranes in general."}
{"id": "PMID:9514", "title": "Proton fluxes associated with erythrocyte membrane anion exchange.", "content": "Transient extracellular pH changes accompany the exchange of chloride for sulfate across the erythrocyte membrane. The direction of the extracellular pH change during chloride efflux and sulfate influx depends on experimental conditions. When bicarbonate is present, the extracellular pH drops sharply at the outset of the anion exchange and tends to follow the partial ionic equilibrium described by Wilbrandt (W. Wilbrandt, 1942. Pfluegers Arch. 246:291). When bicarbonate is absent, however, the anion exchange causes the pH to rise, indicating that protons are cotransported with sulfate during chloride-sulfate exchange. The pH rise can be reversed by the addition of HCO(-3) (4 muM) or 2,4-dinitrophenol (90 muM). This demonstrates that the proton-sulfate cotransport can drive proton transport uphill. The stoichiometry of the transport is that one chloride exchanges for one sulfate plus one proton. These results support the titratable carrier model proposed by Gunn (Gunn, R.B. 1972, In: Oxygen Affinity of Hemoglobin and Red Cell Acid-Base Status. M. Rorth and P. Astrup, editors. p. 823. Munksgaard, Copenhagen) for erythrocyte membrane anion exchange.", "contents": "Proton fluxes associated with erythrocyte membrane anion exchange. Transient extracellular pH changes accompany the exchange of chloride for sulfate across the erythrocyte membrane. The direction of the extracellular pH change during chloride efflux and sulfate influx depends on experimental conditions. When bicarbonate is present, the extracellular pH drops sharply at the outset of the anion exchange and tends to follow the partial ionic equilibrium described by Wilbrandt (W. Wilbrandt, 1942. Pfluegers Arch. 246:291). When bicarbonate is absent, however, the anion exchange causes the pH to rise, indicating that protons are cotransported with sulfate during chloride-sulfate exchange. The pH rise can be reversed by the addition of HCO(-3) (4 muM) or 2,4-dinitrophenol (90 muM). This demonstrates that the proton-sulfate cotransport can drive proton transport uphill. The stoichiometry of the transport is that one chloride exchanges for one sulfate plus one proton. These results support the titratable carrier model proposed by Gunn (Gunn, R.B. 1972, In: Oxygen Affinity of Hemoglobin and Red Cell Acid-Base Status. M. Rorth and P. Astrup, editors. p. 823. Munksgaard, Copenhagen) for erythrocyte membrane anion exchange."}
{"id": "PMID:9519", "title": "Bacteriology and antibiotics in acute suppurative otitis media.", "content": "One hundred and forty-seven patients with acute suppurative otitis media, were divided into three groups and treated with antibiotics (azidocillin, ampicillin, and cephalexin). The therapeutic effect was assessed bacterioloically by swabbing from the aural discharge and from the nasopharynx on the first, second, third, and seventh day after initiation of treatment. In addition, the concentration of antibiotic in the aural discharge and in the nasopharynx was determined. As compared with other published materials, there was a common occurrence of Haemophilus influenzae and S. Aureus. Hemolytic streptococci are less common than prior to the advent of antibiotics. Pneumococci disappeared in all cases from the aural discharge in the course of the first three days. The effect upon Haemophilus was slower. In the nasopharynx the effect was questionable, and no effect was obtained upon other bacteria. The clinical course could not be correlated to the bacterial findings except that resistant bacteria were found in all cases with persisting discharge.", "contents": "Bacteriology and antibiotics in acute suppurative otitis media. One hundred and forty-seven patients with acute suppurative otitis media, were divided into three groups and treated with antibiotics (azidocillin, ampicillin, and cephalexin). The therapeutic effect was assessed bacterioloically by swabbing from the aural discharge and from the nasopharynx on the first, second, third, and seventh day after initiation of treatment. In addition, the concentration of antibiotic in the aural discharge and in the nasopharynx was determined. As compared with other published materials, there was a common occurrence of Haemophilus influenzae and S. Aureus. Hemolytic streptococci are less common than prior to the advent of antibiotics. Pneumococci disappeared in all cases from the aural discharge in the course of the first three days. The effect upon Haemophilus was slower. In the nasopharynx the effect was questionable, and no effect was obtained upon other bacteria. The clinical course could not be correlated to the bacterial findings except that resistant bacteria were found in all cases with persisting discharge."}
{"id": "PMID:9521", "title": "Enzymatic action of coliphage omega8 and its possible role in infection.", "content": "The receptor of coliphage omega8 is the O-specific mannan of Escherichia coli O8 in which the trisaccharide alpha-mannosyl-1,2-alpha-mannosyl-1,2-mannose is joined through alpha-mannosyl-1,3-linkages. Coliphage omega8 produces an endo-alpha-1,3-mannosidase which destroys the receptor, liberating a series of oligosaccharides (repeating trisaccharide and multiples). The enzyme is an integral part of the phage particles and also occurs in a free form in the lysates. Phage particles hydrolyze alpha-1,3-mannosyl linkages in the lipopolysaccharide, the polysaccharide (mannan) moiety, and higher oligosaccharides with an efficiency decreasing in this order. No transmannosylation could be detected. Phage particles also degrade the receptor mannan on whole bacteria, as determined with 14C-labeled E. coli O8. The values of Km and Vmax were determined with omega8 particles and free enzymes using native lipopolysaccharide and its triethylammonium salt. The latter, which was obtained after electrodialysis, has a micellar weight of 2.5 X 10(5), whereas the native lipopolysaccharide forms supermicelles with micellar weights of several millions. With coliphage omega8 as enzyme and supermicellar lipopolysaccharide as substrate Km=5 X 10(-8) M was obtained. This, together with the fact that omega8 attaches irreversibly to E. coli O8, was used in proposing a hypothesis for the possible role of the enzyme in the first steps of infection with coliphage omega8.", "contents": "Enzymatic action of coliphage omega8 and its possible role in infection. The receptor of coliphage omega8 is the O-specific mannan of Escherichia coli O8 in which the trisaccharide alpha-mannosyl-1,2-alpha-mannosyl-1,2-mannose is joined through alpha-mannosyl-1,3-linkages. Coliphage omega8 produces an endo-alpha-1,3-mannosidase which destroys the receptor, liberating a series of oligosaccharides (repeating trisaccharide and multiples). The enzyme is an integral part of the phage particles and also occurs in a free form in the lysates. Phage particles hydrolyze alpha-1,3-mannosyl linkages in the lipopolysaccharide, the polysaccharide (mannan) moiety, and higher oligosaccharides with an efficiency decreasing in this order. No transmannosylation could be detected. Phage particles also degrade the receptor mannan on whole bacteria, as determined with 14C-labeled E. coli O8. The values of Km and Vmax were determined with omega8 particles and free enzymes using native lipopolysaccharide and its triethylammonium salt. The latter, which was obtained after electrodialysis, has a micellar weight of 2.5 X 10(5), whereas the native lipopolysaccharide forms supermicelles with micellar weights of several millions. With coliphage omega8 as enzyme and supermicellar lipopolysaccharide as substrate Km=5 X 10(-8) M was obtained. This, together with the fact that omega8 attaches irreversibly to E. coli O8, was used in proposing a hypothesis for the possible role of the enzyme in the first steps of infection with coliphage omega8."}
{"id": "PMID:9522", "title": "Alpha-adrenoceptor-mediated coronary artery spasm.", "content": "Selective coronary arteriography performed on a 41-year-old woman with angina pectoris demonstrated proximal stenosis of the right and left main coronary arteries that was unaffected by nitrate therapy. To exclude coronary artery spasm, the study was repeated, and a striking increase in the narrowing of the right coronary artery was observed. This 90% stenosis was virtually abolished by pretreatment with intravenously given phentolamine hydrochloride. Prolonged alpha-adrenoceptor blockade with phenoxybenzamine hydrochloride improved the patient's exercise tolerance and postexercise electrocardiographic abnormalities when compared to therapy in matched controls given placebo. These observations suggest that alpha-adrenoceptor-mediated coronary artery spasm may mimic organic lesions at coronary arteriography and may be a factor in the pathogenesis of angina pectoris in some patients.", "contents": "Alpha-adrenoceptor-mediated coronary artery spasm. Selective coronary arteriography performed on a 41-year-old woman with angina pectoris demonstrated proximal stenosis of the right and left main coronary arteries that was unaffected by nitrate therapy. To exclude coronary artery spasm, the study was repeated, and a striking increase in the narrowing of the right coronary artery was observed. This 90% stenosis was virtually abolished by pretreatment with intravenously given phentolamine hydrochloride. Prolonged alpha-adrenoceptor blockade with phenoxybenzamine hydrochloride improved the patient's exercise tolerance and postexercise electrocardiographic abnormalities when compared to therapy in matched controls given placebo. These observations suggest that alpha-adrenoceptor-mediated coronary artery spasm may mimic organic lesions at coronary arteriography and may be a factor in the pathogenesis of angina pectoris in some patients."}
{"id": "PMID:9523", "title": "[In vitro antibacterial effects of spectinomycin and penicillin G on Neisseria gonorrhoeae singly and in combination (author's transl)].", "content": "The antibacterial effects of spectinomycin and penicillin G on clinical isolates of Neisseria gonorrhoeae were studied. The concentrations of penicillin G at which the isolates showed drug sensitivity ranged widely from 0.011 to 6.25 mug/ml. Some of the isolates were resistant to penicillin G. Sensitivity to spectinomycin was observed at the drug concentrations ranging from 3.13 to 12.5 mug/ml. About 60% of the isolates were sensitive to 6.25 mug/ml of spectinomycin, and those isolates which were resistant to penicillin G showed good sensitivity to spectinomycin. No correlation in sensitivity was noted between the two drugs. Tests for their bactericidal activities on bouillon media revealed that the addition of spectinomycin at the concentration of 12.5 mug/ml or over produced a marked bactericidal effect in a short time while penicillin G exhibited a bactericidal or bacteriostatic effect depending upon the concentration used. A synergistic effect of a penicillin and an aminoglycoside antibiotic was observed in these isolates of N. gonorrhoea as was in the isolates of Pseudomonas aeruginosa. Where penicillin G and spectinomycin were used in combination, a simultaneous addition of both the drugs produced the most marked synergistic effect. Morphology of N. gonorrhoeae cells exposed to either of these drugs was examined under a scanning electron microscope. Exposure to spectinomycin at the level of 6.25 mug/ml resulted in almost no morphological change. At 6.25 mug/ml of the drug, however, a roughened cell surface, a bleb-like structure or a state suggesting the loosening of such a bleb-like structure was noted. The addition of penicillin G at 0.19 mug/ml led to an impairment of cell division at one hour of exposure and to cell swelling and lysis with further exposure. At 1.19 mug/ml of the drug, these processes of cell swelling and lysis took place early.", "contents": "[In vitro antibacterial effects of spectinomycin and penicillin G on Neisseria gonorrhoeae singly and in combination (author's transl)]. The antibacterial effects of spectinomycin and penicillin G on clinical isolates of Neisseria gonorrhoeae were studied. The concentrations of penicillin G at which the isolates showed drug sensitivity ranged widely from 0.011 to 6.25 mug/ml. Some of the isolates were resistant to penicillin G. Sensitivity to spectinomycin was observed at the drug concentrations ranging from 3.13 to 12.5 mug/ml. About 60% of the isolates were sensitive to 6.25 mug/ml of spectinomycin, and those isolates which were resistant to penicillin G showed good sensitivity to spectinomycin. No correlation in sensitivity was noted between the two drugs. Tests for their bactericidal activities on bouillon media revealed that the addition of spectinomycin at the concentration of 12.5 mug/ml or over produced a marked bactericidal effect in a short time while penicillin G exhibited a bactericidal or bacteriostatic effect depending upon the concentration used. A synergistic effect of a penicillin and an aminoglycoside antibiotic was observed in these isolates of N. gonorrhoea as was in the isolates of Pseudomonas aeruginosa. Where penicillin G and spectinomycin were used in combination, a simultaneous addition of both the drugs produced the most marked synergistic effect. Morphology of N. gonorrhoeae cells exposed to either of these drugs was examined under a scanning electron microscope. Exposure to spectinomycin at the level of 6.25 mug/ml resulted in almost no morphological change. At 6.25 mug/ml of the drug, however, a roughened cell surface, a bleb-like structure or a state suggesting the loosening of such a bleb-like structure was noted. The addition of penicillin G at 0.19 mug/ml led to an impairment of cell division at one hour of exposure and to cell swelling and lysis with further exposure. At 1.19 mug/ml of the drug, these processes of cell swelling and lysis took place early."}
{"id": "PMID:9524", "title": "Absence of blocking effect of quinidine on responses to norepinephrine in the isolated dog atrium.", "content": "The isolated right dog atrium was perfused through the sinus node artery with blood led from a heparinized support dog under constant perfusion pressure of 100 mmHg. The positive chronotropic and inotropic responses to norepinephrine were not significantly suppressed by treatment with large amounts of quinidine or procainamide, but completely blocked by propranolol. From these results, it was demonstrated that quinidine and procainamide have no adrenergic beta-blocking activity on chronotropism and on inotropism in the heart.", "contents": "Absence of blocking effect of quinidine on responses to norepinephrine in the isolated dog atrium. The isolated right dog atrium was perfused through the sinus node artery with blood led from a heparinized support dog under constant perfusion pressure of 100 mmHg. The positive chronotropic and inotropic responses to norepinephrine were not significantly suppressed by treatment with large amounts of quinidine or procainamide, but completely blocked by propranolol. From these results, it was demonstrated that quinidine and procainamide have no adrenergic beta-blocking activity on chronotropism and on inotropism in the heart."}
{"id": "PMID:9520", "title": "[Intra-renal arterio-venous aneurysm after renal puncture biopsy. Supra-selective embolization. Cure (author's transl)].", "content": "This case emphasizes the value of: 1. Treatment of malignant hypertension with the combination of hemodialysis and beta-blockers. 2. Supra-selective arterial embolization in inaccessible intra-renal aneurysms or those difficulty accessible to surgery.", "contents": "[Intra-renal arterio-venous aneurysm after renal puncture biopsy. Supra-selective embolization. Cure (author's transl)]. This case emphasizes the value of: 1. Treatment of malignant hypertension with the combination of hemodialysis and beta-blockers. 2. Supra-selective arterial embolization in inaccessible intra-renal aneurysms or those difficulty accessible to surgery."}
{"id": "PMID:9528", "title": "Effect of capsular polysaccharide of Klebsiella pneumoniae on host resistance to bacterial infections. I. Induction of increased susceptibility to infections in mice.", "content": "When Klebsiella pneumoniae capsular polysaccharide (CPS-K) from type 1, Kasuya strain, was injected intraperitoneally (i.p.) immediately before i.p. bacterial challenge, the survival time of mice infected with Salmonella enteritidis NUB 1 (virulent strain) was shortened and the mortality rate for mice infected with S. enteritidis NUB 31 (avirulent strain) was enhanced. The promotion of infection with S. enteritidis NUB 1 by CPS-K depended upon its dose, the effect of CPS-K being demonstrable up to as little as 0.2 mug per mouse. In the case of S. enteritidis NUB 31, the effect of CPS-K was detectable only when more than 20 mug per mouse was injected. As a result of enumeration of bacterial populations in the peritoneal washing, blood, liver and spleen, it was revealed that CPS-K promoted in vivo growth of S. enteritidis NUB 1 and NUB 31. In addition, CPS-K enhanced the mortality rate in mice infected with Streptococcus pyogenes or Streptococcus pneumoniae. The peak CPS-K effect on infection with S. enteritidis NUB 1 was seen when given immediately before bacterial challenge. The active substance responsible for the infection-promoting effect of CPS-K was neutral CPS-K, which is distinct from the O antigen and from acidic CPS-K (the type-specific capsular antigen). Preparations of neutral CPS-K isolated from the other three strains of K. pneumoniae exhibited a marked infection-promoting effect comparable with that of preparations from the Kasuya strain. Neutral CPS-K, with identical antigenicity to that from the Kasuya strain, has already been found to exert a strong adjuvant effect on antibody responses to various antigens in mice. No parallelism exists between infection-promoting activity and adjuvant activity of neutral CPS-K.", "contents": "Effect of capsular polysaccharide of Klebsiella pneumoniae on host resistance to bacterial infections. I. Induction of increased susceptibility to infections in mice. When Klebsiella pneumoniae capsular polysaccharide (CPS-K) from type 1, Kasuya strain, was injected intraperitoneally (i.p.) immediately before i.p. bacterial challenge, the survival time of mice infected with Salmonella enteritidis NUB 1 (virulent strain) was shortened and the mortality rate for mice infected with S. enteritidis NUB 31 (avirulent strain) was enhanced. The promotion of infection with S. enteritidis NUB 1 by CPS-K depended upon its dose, the effect of CPS-K being demonstrable up to as little as 0.2 mug per mouse. In the case of S. enteritidis NUB 31, the effect of CPS-K was detectable only when more than 20 mug per mouse was injected. As a result of enumeration of bacterial populations in the peritoneal washing, blood, liver and spleen, it was revealed that CPS-K promoted in vivo growth of S. enteritidis NUB 1 and NUB 31. In addition, CPS-K enhanced the mortality rate in mice infected with Streptococcus pyogenes or Streptococcus pneumoniae. The peak CPS-K effect on infection with S. enteritidis NUB 1 was seen when given immediately before bacterial challenge. The active substance responsible for the infection-promoting effect of CPS-K was neutral CPS-K, which is distinct from the O antigen and from acidic CPS-K (the type-specific capsular antigen). Preparations of neutral CPS-K isolated from the other three strains of K. pneumoniae exhibited a marked infection-promoting effect comparable with that of preparations from the Kasuya strain. Neutral CPS-K, with identical antigenicity to that from the Kasuya strain, has already been found to exert a strong adjuvant effect on antibody responses to various antigens in mice. No parallelism exists between infection-promoting activity and adjuvant activity of neutral CPS-K."}
{"id": "PMID:9538", "title": "A critical examination of some current assumptions in the treatment of alcoholism.", "content": "Recent scientific research challenges a number of traditional assumptions in the treatment of alcoholism. Two major tenets, the disease conception of alcoholism and mandatory abstinence as a goal of treatment are reviewed, and insufficient evidence is found to support a dogmatic position on either.", "contents": "A critical examination of some current assumptions in the treatment of alcoholism. Recent scientific research challenges a number of traditional assumptions in the treatment of alcoholism. Two major tenets, the disease conception of alcoholism and mandatory abstinence as a goal of treatment are reviewed, and insufficient evidence is found to support a dogmatic position on either."}
{"id": "PMID:9533", "title": "[Biological properties of Cl. perfringens type A, isolated from human subjects inhabiting a hermetic chamber].", "content": "This paper gives the results of quantifying and studying the biological properties of Cl. perfringens strains isolated from feces of test subjects kept in an enclosure for 34 days. During the experiment the total number of Cl. perfringens increased. It was especially true of the strains with an elevated toxigenic activity. This activity correlated with an increase of the titer of alpha-hemolysines and proteolytic enzymes.", "contents": "[Biological properties of Cl. perfringens type A, isolated from human subjects inhabiting a hermetic chamber]. This paper gives the results of quantifying and studying the biological properties of Cl. perfringens strains isolated from feces of test subjects kept in an enclosure for 34 days. During the experiment the total number of Cl. perfringens increased. It was especially true of the strains with an elevated toxigenic activity. This activity correlated with an increase of the titer of alpha-hemolysines and proteolytic enzymes."}
{"id": "PMID:9555", "title": "Interactions of phospholipase D with 1,2 diacyl-sn-glycerol-3-phosphorylcholine, dodecylsulfate, and Ca2+.", "content": "Some properties of the pure, soluble phospholipase D (phosphatidycholine phosphatido hydrolase, EC 3.1.4.4) interactions with phosphatidyl choline (1,2 diacyl-sn-glycerol-3-phosphoryl choline) in a system also containing dodecylsulfate and Ca2+ ions were studied. Concentrations of Ca2+ greater than 50 mM were necessary both for activity and adsorption of the enzyme to the \"supersubstrate.\" Ethylenediamine tetraacetic acid caused inhibition of activity, greater than one would expect from its chelating capacity. A nonlinear increase in activity with the increase of enzyme protein was observed, suggesting a subunit aggregation into a higher mol wt protein, catalytically more active. Upon centrifugation of the supersubstrate-enzyme complex at 4.5 X 10(5) g-min at 30 C, most of the substrate molecules sedimented regardless of the pH. The reverse was true when centrifugation was done at 1 C. Phospholipase D hydrolyzed phosphatidylcholine molecules present in the supersubstrate at temperatures around 0 C at a rate 1/5 that of a maximal value measured at 30 C. The Arrhenius plot was linear in the range from 0 to 30 C, and at that temperature the curve broke with a smaller slope. Activation energy of 9.1 Kcal/mol, below 30 C, was calculated. Adsorption of the enzyme to the sedimentable supersubstrate occurred at pH 8.0, regardless of temperature. At pH 5.6, a considerable portion of phosphatidylcholine was degraded at 30 C, thus minimizing the capacity of the supersubstrate to adsorb the enzyme. Although Mg2+ could replace Ca2+ in the formation of sedimentable supersubstrate, it neither assists in adsorption of the enzyme nor in activation of the phosphatidylcholine hydrolysis.", "contents": "Interactions of phospholipase D with 1,2 diacyl-sn-glycerol-3-phosphorylcholine, dodecylsulfate, and Ca2+. Some properties of the pure, soluble phospholipase D (phosphatidycholine phosphatido hydrolase, EC 3.1.4.4) interactions with phosphatidyl choline (1,2 diacyl-sn-glycerol-3-phosphoryl choline) in a system also containing dodecylsulfate and Ca2+ ions were studied. Concentrations of Ca2+ greater than 50 mM were necessary both for activity and adsorption of the enzyme to the \"supersubstrate.\" Ethylenediamine tetraacetic acid caused inhibition of activity, greater than one would expect from its chelating capacity. A nonlinear increase in activity with the increase of enzyme protein was observed, suggesting a subunit aggregation into a higher mol wt protein, catalytically more active. Upon centrifugation of the supersubstrate-enzyme complex at 4.5 X 10(5) g-min at 30 C, most of the substrate molecules sedimented regardless of the pH. The reverse was true when centrifugation was done at 1 C. Phospholipase D hydrolyzed phosphatidylcholine molecules present in the supersubstrate at temperatures around 0 C at a rate 1/5 that of a maximal value measured at 30 C. The Arrhenius plot was linear in the range from 0 to 30 C, and at that temperature the curve broke with a smaller slope. Activation energy of 9.1 Kcal/mol, below 30 C, was calculated. Adsorption of the enzyme to the sedimentable supersubstrate occurred at pH 8.0, regardless of temperature. At pH 5.6, a considerable portion of phosphatidylcholine was degraded at 30 C, thus minimizing the capacity of the supersubstrate to adsorb the enzyme. Although Mg2+ could replace Ca2+ in the formation of sedimentable supersubstrate, it neither assists in adsorption of the enzyme nor in activation of the phosphatidylcholine hydrolysis."}
{"id": "PMID:9556", "title": "Studies on drug-induced lipidosis: VII. Effects of bis-beta-diethyl-aminoethylether of hexestrol, chloroquine, homochlorocyclizine, prenylamine, and diazacholesterol on the lipid composition of rat liver and kidney.", "content": "4,4'-Bis (beta-diethylaminoethoxy)-alpha, beta-diethyldiphenylethane (DH), which had been shown to induce a type of lipidosis resembling Niemann-Pick disease, was given to rats at a dose of 20, 50, 100, and 150 mg/kg body weight per day for 1 or 2 weeks. An enlargement of the liver with marked increases in free cholesterol, total phospholipids, and phosphatidylinositol took place by administration of a larger dose. The increase in bis (monoacylglyceryl) phosphate (BMGP), which is peculiar to this kind of drug-induced lipidosis, was dependent upon the dose of the drug as well as the length of time. Similar changes were also observed in kidney. Among several other drugs tested, chloroquine and diazacholesterol brought on as much increase in BMGP as treatment with DH.", "contents": "Studies on drug-induced lipidosis: VII. Effects of bis-beta-diethyl-aminoethylether of hexestrol, chloroquine, homochlorocyclizine, prenylamine, and diazacholesterol on the lipid composition of rat liver and kidney. 4,4'-Bis (beta-diethylaminoethoxy)-alpha, beta-diethyldiphenylethane (DH), which had been shown to induce a type of lipidosis resembling Niemann-Pick disease, was given to rats at a dose of 20, 50, 100, and 150 mg/kg body weight per day for 1 or 2 weeks. An enlargement of the liver with marked increases in free cholesterol, total phospholipids, and phosphatidylinositol took place by administration of a larger dose. The increase in bis (monoacylglyceryl) phosphate (BMGP), which is peculiar to this kind of drug-induced lipidosis, was dependent upon the dose of the drug as well as the length of time. Similar changes were also observed in kidney. Among several other drugs tested, chloroquine and diazacholesterol brought on as much increase in BMGP as treatment with DH."}
{"id": "PMID:9559", "title": "Role of the parietal cell in gastric damage induced by aspirin and related drugs: implications for safer therapy.", "content": "The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is due to the ph gradient favouring a high rate of aspirin uptake and subsequent entrapment of drug anions inside these cells. This concept may serve as a useful basis for developing procedures to minimize the gastric damage by aspirin and related acidic drugs.", "contents": "Role of the parietal cell in gastric damage induced by aspirin and related drugs: implications for safer therapy. The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is due to the ph gradient favouring a high rate of aspirin uptake and subsequent entrapment of drug anions inside these cells. This concept may serve as a useful basis for developing procedures to minimize the gastric damage by aspirin and related acidic drugs."}
{"id": "PMID:9558", "title": "Schizophrenic psychology, associative learning and the role of forebrain dopamine.", "content": "It is suggested that schizophrenic thinking can be explained as a lowering of levels of significance for acceptance of conclusions based on inductive logic. The formal similarity between inductive logic and operant, or classical conditioning is pointed out. It is thus possible to explain the therapeutic effects of neuroleptic drugs by referring to the effect of these, and related drugs, and of lesions of ascending dopamine pathways, on acquisition of conditioned responses. It is tentatively suggested that recognition of association of related features of the environment, whether in humans or animals occurs in the basal ganglia by a dopamine dependent process. A role is suggested for neocortical noradrenaline in consolidaton of newly acquired associations. Implications and tests of this hypothesis are discussed.", "contents": "Schizophrenic psychology, associative learning and the role of forebrain dopamine. It is suggested that schizophrenic thinking can be explained as a lowering of levels of significance for acceptance of conclusions based on inductive logic. The formal similarity between inductive logic and operant, or classical conditioning is pointed out. It is thus possible to explain the therapeutic effects of neuroleptic drugs by referring to the effect of these, and related drugs, and of lesions of ascending dopamine pathways, on acquisition of conditioned responses. It is tentatively suggested that recognition of association of related features of the environment, whether in humans or animals occurs in the basal ganglia by a dopamine dependent process. A role is suggested for neocortical noradrenaline in consolidaton of newly acquired associations. Implications and tests of this hypothesis are discussed."}
{"id": "PMID:9581", "title": "Two weeks' treatment with chlorpromazine, thioridazine, sulpiride, or bromazepam: actions and interactions with alcohol on psychomotor skills related to driving.", "content": "Subacute effects of C, T, S, or B, alone or in combination with A, were tested against P in two double-blind crossover trials with 37 healthy students. The drugs were given in capsules t.i.d. for 2 weeks each and the psychomotor performance (choice reaction, coordination, attention) was measured on the 7th and 14th days of treatment. At each session the subjects swallowed a capsule together with 0.5 g/kg of A or P drink, and the measurements were done, 30, 90, and 150 min thereafter. T alone did not differ from placebo in the doses used (10 mg t.i.d. for 7 days and 20 mg t.i.d. for the next 7 days). After C (dosing as above) and S (50 mg t.i.d.) both reactive and coordinative skills were slightly impaired. B (6 mg t.i.d.) clearly impaired both reactive skills and attention. T + A had no major combined effect on skills while C interacted with A resulting in impaired reactive and coordinative skills. After C + A the subjects were unable of compensating their coordination mistakes by slow driving. The interaction of S with A was mild, whereas B + A strongly impaired coordination and divided attention. No alterations were recorded in flicker fusion after any treatment.", "contents": "Two weeks' treatment with chlorpromazine, thioridazine, sulpiride, or bromazepam: actions and interactions with alcohol on psychomotor skills related to driving. Subacute effects of C, T, S, or B, alone or in combination with A, were tested against P in two double-blind crossover trials with 37 healthy students. The drugs were given in capsules t.i.d. for 2 weeks each and the psychomotor performance (choice reaction, coordination, attention) was measured on the 7th and 14th days of treatment. At each session the subjects swallowed a capsule together with 0.5 g/kg of A or P drink, and the measurements were done, 30, 90, and 150 min thereafter. T alone did not differ from placebo in the doses used (10 mg t.i.d. for 7 days and 20 mg t.i.d. for the next 7 days). After C (dosing as above) and S (50 mg t.i.d.) both reactive and coordinative skills were slightly impaired. B (6 mg t.i.d.) clearly impaired both reactive skills and attention. T + A had no major combined effect on skills while C interacted with A resulting in impaired reactive and coordinative skills. After C + A the subjects were unable of compensating their coordination mistakes by slow driving. The interaction of S with A was mild, whereas B + A strongly impaired coordination and divided attention. No alterations were recorded in flicker fusion after any treatment."}
{"id": "PMID:9583", "title": "[Longterm therapy of angina pectoris patients with a new beta-receptor blocker (author's transl)].", "content": "The beta-receptor blocker Timolol was investigated for 28 weeks in a double blind trial and then for up to 100 weeks in an open trial in patients with angina pectoris. In both phases of the investigation. Timolol caused a quite marked regression in the frequency of attacks and in the pulse rate at rest. The evaluation of therapeutic success by doctor and patient was positive for Timolol.", "contents": "[Longterm therapy of angina pectoris patients with a new beta-receptor blocker (author's transl)]. The beta-receptor blocker Timolol was investigated for 28 weeks in a double blind trial and then for up to 100 weeks in an open trial in patients with angina pectoris. In both phases of the investigation. Timolol caused a quite marked regression in the frequency of attacks and in the pulse rate at rest. The evaluation of therapeutic success by doctor and patient was positive for Timolol."}
{"id": "PMID:9584", "title": "[Angina pectoris. Results of investigations to date (author's transl)].", "content": "Among the most important coronary risk factors are a diet rich in saturated fatty acids, cholesterol and calories, hypercholesterolemia, high blood pressure and excessive smoking. The typical pain can be elicited by putting a strain on the patient, e.g. climbing stairs. The disappearance of the pain after treatment with nitroglycerine is one of the most important pointers. Treatment is with nitroglycerine which, moreover, remains the drug of choice, also with nitrates such as pentaerythritol tetranitrate and with betablockers like propranolol. Favorable results have also been reported with a combination of isosorbide dinitrate and propranolol.", "contents": "[Angina pectoris. Results of investigations to date (author's transl)]. Among the most important coronary risk factors are a diet rich in saturated fatty acids, cholesterol and calories, hypercholesterolemia, high blood pressure and excessive smoking. The typical pain can be elicited by putting a strain on the patient, e.g. climbing stairs. The disappearance of the pain after treatment with nitroglycerine is one of the most important pointers. Treatment is with nitroglycerine which, moreover, remains the drug of choice, also with nitrates such as pentaerythritol tetranitrate and with betablockers like propranolol. Favorable results have also been reported with a combination of isosorbide dinitrate and propranolol."}
{"id": "PMID:9593", "title": "[Self cleaning of natural waters].", "content": "The planting of the waters left the question open as to whether the necessary expenditure of work is really worthwhile and should be encouraged. The investigations reported here with higher and particularly emersed plants, show what an astonishing influence the higher plants exert on organic and inorganic matter, on pH regulation, destruction of pathogenic bacteria, worms' eggs, and viruses, and also how they influence the waters and waste waters.", "contents": "[Self cleaning of natural waters]. The planting of the waters left the question open as to whether the necessary expenditure of work is really worthwhile and should be encouraged. The investigations reported here with higher and particularly emersed plants, show what an astonishing influence the higher plants exert on organic and inorganic matter, on pH regulation, destruction of pathogenic bacteria, worms' eggs, and viruses, and also how they influence the waters and waste waters."}
{"id": "PMID:9594", "title": "Lichens as indicators of air pollution.", "content": "Field and laboratory studies have demonstrated that lichens are extremely sensitive to sulfur dioxide and that lichens are fairly sensitive to hydrogen fluoride and heavy metals. Further studies are necessary to assess lichens' relative sensitivity to oxidant air pollutants.", "contents": "Lichens as indicators of air pollution. Field and laboratory studies have demonstrated that lichens are extremely sensitive to sulfur dioxide and that lichens are fairly sensitive to hydrogen fluoride and heavy metals. Further studies are necessary to assess lichens' relative sensitivity to oxidant air pollutants."}
{"id": "PMID:9595", "title": "Molecular sensory physiology of Euglena.", "content": "After a short description of the motile physiology of Euglena gracilis the responses to light stimulation are analyzed and a new nomenclature is proposed concerning flagellar motility variations. A discussion follows about the characteristics of the photoreceptive system of Euglena and about the flavinic nature of its phototactic pigments.", "contents": "Molecular sensory physiology of Euglena. After a short description of the motile physiology of Euglena gracilis the responses to light stimulation are analyzed and a new nomenclature is proposed concerning flagellar motility variations. A discussion follows about the characteristics of the photoreceptive system of Euglena and about the flavinic nature of its phototactic pigments."}
{"id": "PMID:9597", "title": "[Apudomas].", "content": "Apudomas, i.e. tumours deriving from apud system cells, comprise already known forms located in widely different organs at considerable distances one from the other. They present great cytochemical, biochemical and ultrastructural similarities and possess a common derivation in the neuroectodermal cells of the neural crest. They thus form part of that tumour group known as neurolophomas. They are also responsible for typical clinical pictures connected with the production of hormone-type substances, and are classified among multiple endocrine adenomatoses and in the ectopic hormone syndromes.", "contents": "[Apudomas]. Apudomas, i.e. tumours deriving from apud system cells, comprise already known forms located in widely different organs at considerable distances one from the other. They present great cytochemical, biochemical and ultrastructural similarities and possess a common derivation in the neuroectodermal cells of the neural crest. They thus form part of that tumour group known as neurolophomas. They are also responsible for typical clinical pictures connected with the production of hormone-type substances, and are classified among multiple endocrine adenomatoses and in the ectopic hormone syndromes."}
{"id": "PMID:9598", "title": "[Critical observations on changes in gamma-glutamyl-transpepdidase in hepatopathies].", "content": "The behaviour of gamma-glutamyl transpeptidase was compared with other serum enzyme activities and functional parameters in a carefully selected and relatively extensive series of patients with liver disease, including alcoholics, in an investigation of the underlying pathogenesis and its clinical expression. Reference. to the literature and to personal data showed that increased gamma-glutamyl transpeptidase levels could be attributed to enzyme induction (caused by drugs or alcohol), liver damage in the broad sense, and intra- or extrahepatic cholestasis. These causes were individually predominant, or nearly so, on occasions, though their concomitance was more common. High levels, however, were not pathognomonic for a given disease. In alcoholism, they were highly indicative, especially if accompanied by GLD changes. They were a virtually constant, early, and typical finding in intra- and extra-hepatic cholestasis, and tended to persist for a time after the resolution of icterus. Lastly, they were an aid in the early diagnosis of aggressive hepatitis and liver cancer.", "contents": "[Critical observations on changes in gamma-glutamyl-transpepdidase in hepatopathies]. The behaviour of gamma-glutamyl transpeptidase was compared with other serum enzyme activities and functional parameters in a carefully selected and relatively extensive series of patients with liver disease, including alcoholics, in an investigation of the underlying pathogenesis and its clinical expression. Reference. to the literature and to personal data showed that increased gamma-glutamyl transpeptidase levels could be attributed to enzyme induction (caused by drugs or alcohol), liver damage in the broad sense, and intra- or extrahepatic cholestasis. These causes were individually predominant, or nearly so, on occasions, though their concomitance was more common. High levels, however, were not pathognomonic for a given disease. In alcoholism, they were highly indicative, especially if accompanied by GLD changes. They were a virtually constant, early, and typical finding in intra- and extra-hepatic cholestasis, and tended to persist for a time after the resolution of icterus. Lastly, they were an aid in the early diagnosis of aggressive hepatitis and liver cancer."}
{"id": "PMID:9599", "title": "[Changes in partial pressures of gases and of pH in the arterial blood of hypocapnic and hypercapnic subjects subjected to oxygen therapy].", "content": "The behaviour of partial tensions of respiratory gases and pH in the arterial blood was evaluated in anoxiaemic and hypercapnic (1st group) and hypo-eucapnic (IInd group) subjects undergoing oxygen therapy. The following phenomena were observed: 1) normalization in paO2 values in both groups; 2) statistically significant diminution in paCO2, especially as regards hypercapnic subjects; 3) statistically significant diminution in blood pH; 4) statistically significant diminution in bicarbonates. In the light of these findings, it is considered that other variables, such as the electrolytes, might play an important role in pH diminution during oxygen therapy and that further research should be carried out to look into the possibility.", "contents": "[Changes in partial pressures of gases and of pH in the arterial blood of hypocapnic and hypercapnic subjects subjected to oxygen therapy]. The behaviour of partial tensions of respiratory gases and pH in the arterial blood was evaluated in anoxiaemic and hypercapnic (1st group) and hypo-eucapnic (IInd group) subjects undergoing oxygen therapy. The following phenomena were observed: 1) normalization in paO2 values in both groups; 2) statistically significant diminution in paCO2, especially as regards hypercapnic subjects; 3) statistically significant diminution in blood pH; 4) statistically significant diminution in bicarbonates. In the light of these findings, it is considered that other variables, such as the electrolytes, might play an important role in pH diminution during oxygen therapy and that further research should be carried out to look into the possibility."}
{"id": "PMID:9600", "title": "[Changes in acid-base equilibrium of the arterial blood in hypoxemic-eucapnic subjects subjected to oxygen therapy with and without an antiphosphodiesterase drug].", "content": "The behaviour of the partial tensions of respiratory gases and the main parameters of acid base balance in hypoxaemic and eucapnic chronic bronchopneumopathics undergoing oxygen therapy has been assessed. The patiests were subdivided into two groups, the first consisting of subjects undergoing oxygen therapy alone, the second of subjects having oxygen and i.v. theophylline at the same time. Two subgroups were also distinguished. These consisted respectively of normochloraemic and hypochloraemic patients, the purpose being to reveal whether electrolytic changes could be attributed to the  concentration of chlorine evaluated in basal conditions. The results obtained showed a disappearance of the hypoxaemic state without appreciable changes in paCO2 in all patients; in those undergoing oxygen therapy only, also observed were: 1) increase in plasmatic H+ and reduction in pH; 2) diminution in HCO3- and plasma Na+; 3) increase in plasma concentration of Cl-; 4)  statistical significance of these data; 5) tendency of all values in the parameters considered to return to basal values upon suspension of oxygenation.", "contents": "[Changes in acid-base equilibrium of the arterial blood in hypoxemic-eucapnic subjects subjected to oxygen therapy with and without an antiphosphodiesterase drug]. The behaviour of the partial tensions of respiratory gases and the main parameters of acid base balance in hypoxaemic and eucapnic chronic bronchopneumopathics undergoing oxygen therapy has been assessed. The patiests were subdivided into two groups, the first consisting of subjects undergoing oxygen therapy alone, the second of subjects having oxygen and i.v. theophylline at the same time. Two subgroups were also distinguished. These consisted respectively of normochloraemic and hypochloraemic patients, the purpose being to reveal whether electrolytic changes could be attributed to the  concentration of chlorine evaluated in basal conditions. The results obtained showed a disappearance of the hypoxaemic state without appreciable changes in paCO2 in all patients; in those undergoing oxygen therapy only, also observed were: 1) increase in plasmatic H+ and reduction in pH; 2) diminution in HCO3- and plasma Na+; 3) increase in plasma concentration of Cl-; 4)  statistical significance of these data; 5) tendency of all values in the parameters considered to return to basal values upon suspension of oxygenation."}
{"id": "PMID:9601", "title": "[Gasometric changes and acid-base equilibrium of venous blood oxygenated in vitro and incubated with or without a phosphodiesterase inhibitor].", "content": "Changes in partial tension of the respiratory gases and in acid-base balance were studied in venous blood subjected to oxygenation, with or without incubation with theophylline. The following modifications were noted: 1) increased pO2; 2) decreased CO2 due to true wash-out caused by tonometry in oxygen; 3)decreased hydrogen ion concentration and bicarbonates following CO2 washing in both experimental models. A smaller reduction in pH and HCO3 was statistically significant in specimens treated with theophylline. This is seen as proof of the view that theophylline inhibits red cell membrane ion exchanges, such as to oppose or at any rate limit metabolic changes in acid-base balance induced by oxygenation.", "contents": "[Gasometric changes and acid-base equilibrium of venous blood oxygenated in vitro and incubated with or without a phosphodiesterase inhibitor]. Changes in partial tension of the respiratory gases and in acid-base balance were studied in venous blood subjected to oxygenation, with or without incubation with theophylline. The following modifications were noted: 1) increased pO2; 2) decreased CO2 due to true wash-out caused by tonometry in oxygen; 3)decreased hydrogen ion concentration and bicarbonates following CO2 washing in both experimental models. A smaller reduction in pH and HCO3 was statistically significant in specimens treated with theophylline. This is seen as proof of the view that theophylline inhibits red cell membrane ion exchanges, such as to oppose or at any rate limit metabolic changes in acid-base balance induced by oxygenation."}
{"id": "PMID:9602", "title": "[Acid-base equilibrium of the arterial blood of subjects with grave hypercapnia subjected to mechanical ventilation with the iron lung (concerning 2 cases of post-hypercapnic alkalosis)].", "content": "Two cases of severe chronic respiratory insufficiency in severely acute phase with disturbances in acid base balance characterized by serious gaseous acidosis are reported. Therapy was based essentially on controlled ventilotherapy using an iron lung and considerable improvements were achieved clinically with practically total normalization of the acid base imbalance after only a few hours of treatment. In the following days, however, a picture of metabolic alkalosis established itself and this is discussed and interpreted as an expression of post-hypercapnic hypochloraemia.", "contents": "[Acid-base equilibrium of the arterial blood of subjects with grave hypercapnia subjected to mechanical ventilation with the iron lung (concerning 2 cases of post-hypercapnic alkalosis)]. Two cases of severe chronic respiratory insufficiency in severely acute phase with disturbances in acid base balance characterized by serious gaseous acidosis are reported. Therapy was based essentially on controlled ventilotherapy using an iron lung and considerable improvements were achieved clinically with practically total normalization of the acid base imbalance after only a few hours of treatment. In the following days, however, a picture of metabolic alkalosis established itself and this is discussed and interpreted as an expression of post-hypercapnic hypochloraemia."}
{"id": "PMID:9604", "title": "Measurement of pituitary hormones: clinical applications. 5. Prolactin.", "content": "A sensitive and specific assay for human prolactin has been developed using human prolactin and antiserum distributed by the United States National Pituitary Agency. Plasma prolactin concentrations in control subjects ranged from 0-20 ng/ml. No sex difference in prolactin concentration was observed. A brisk increase in plasma prolactin levels occurred in normal subjects during the administration of chlorpromazine and thyroid stimulating hormone releasing factor (TRH). These stimulatory tests of prolactin release should therefore be useful in the assessment of hypothalamic pituitary function. Basal plasma prolactin values were raised in most patients who were being treated with phenothiazines and were helpful diagnostically in patients with amenorrhoea, galactorrhoea, hypogonadism, cranio-pharyngioma, \"non-functioning\" pituitary tumours and acromegaly. In many of these disorders a significant reduction in the plasma prolactin concentration was observed following oral administration of bromocriptine. Plasma prolactin determinations should be useful in evaluating the response to medical treatment or pituitary ablation.", "contents": "Measurement of pituitary hormones: clinical applications. 5. Prolactin. A sensitive and specific assay for human prolactin has been developed using human prolactin and antiserum distributed by the United States National Pituitary Agency. Plasma prolactin concentrations in control subjects ranged from 0-20 ng/ml. No sex difference in prolactin concentration was observed. A brisk increase in plasma prolactin levels occurred in normal subjects during the administration of chlorpromazine and thyroid stimulating hormone releasing factor (TRH). These stimulatory tests of prolactin release should therefore be useful in the assessment of hypothalamic pituitary function. Basal plasma prolactin values were raised in most patients who were being treated with phenothiazines and were helpful diagnostically in patients with amenorrhoea, galactorrhoea, hypogonadism, cranio-pharyngioma, \"non-functioning\" pituitary tumours and acromegaly. In many of these disorders a significant reduction in the plasma prolactin concentration was observed following oral administration of bromocriptine. Plasma prolactin determinations should be useful in evaluating the response to medical treatment or pituitary ablation."}
{"id": "PMID:9605", "title": "Correlation of fetal heart rate patterns and fetal pH with neonatal outcome.", "content": "Fetal monitoring data in 200 consecutive cases was evaluated in the second hour prior to delivery to determine how neonatal outcome could be most accurately predicted. It was found that the correlation between ominous fetal heart rate-uterine contraction (FHR-UC) patterns and a depressed Apgar score at 1 minute was, at best, 37%. However, where the last fetal scalp blood pH (FSB-pH) was less than or equal to 7.2, neonatal depression occurred in 88% of cases. FSB-pH, therefore, provided a more reliable means of diagnosing fetal distress.", "contents": "Correlation of fetal heart rate patterns and fetal pH with neonatal outcome. Fetal monitoring data in 200 consecutive cases was evaluated in the second hour prior to delivery to determine how neonatal outcome could be most accurately predicted. It was found that the correlation between ominous fetal heart rate-uterine contraction (FHR-UC) patterns and a depressed Apgar score at 1 minute was, at best, 37%. However, where the last fetal scalp blood pH (FSB-pH) was less than or equal to 7.2, neonatal depression occurred in 88% of cases. FSB-pH, therefore, provided a more reliable means of diagnosing fetal distress."}
{"id": "PMID:9614", "title": "The detection of toxin production by Corynebacterium diphtheriae in diagnostic laboratories.", "content": "In vitro tests for assessing the toxigenicity of strains of C. diphtheriae using the original agar plate precipitin method of Elek are unreliable. At high concentrations of antitoxin (500-1000 U/ml) multiple non-specific precipitin lines occur making interpretation difficult. Increased specificity was obtained by diluting the antitoxin but this in turn caused a delay in the appearance of toxin-antitoxin lines. Also, the failure of lines to appear on media enriched with unsuitable serum may lead to false-negative results. Final assessment of the toxigenicity of strains of C. diphtheriae can probably only be made reliably by guinea-pig tests.", "contents": "The detection of toxin production by Corynebacterium diphtheriae in diagnostic laboratories. In vitro tests for assessing the toxigenicity of strains of C. diphtheriae using the original agar plate precipitin method of Elek are unreliable. At high concentrations of antitoxin (500-1000 U/ml) multiple non-specific precipitin lines occur making interpretation difficult. Increased specificity was obtained by diluting the antitoxin but this in turn caused a delay in the appearance of toxin-antitoxin lines. Also, the failure of lines to appear on media enriched with unsuitable serum may lead to false-negative results. Final assessment of the toxigenicity of strains of C. diphtheriae can probably only be made reliably by guinea-pig tests."}
{"id": "PMID:9619", "title": "Defective polymorphonuclear leukocyte chemotaxis and bactericidal capacity in a boy with recurrent pyogenic infections.", "content": "A 13-year-old boy with a history of recurrent pyogenic infections had abnormalities of polymorphonuclear leukocyte (PMN) function which probably accounted for his susceptibility to infection. PMN phagocytosis and nitroblue tetrazolium dye reduction were normal but glucose 14C oxidation was abnormally increased in resting cells. The patient's PMNs possessed decreased bactericidal activity against Staphylococcus aureus and Escherichia coli. Also documented were decreased PMN chemotactic activity and leukocyte accumulation in Rebuck skin windows. PMN random motility, PMN bone marrow reserve, PMN kinetics, lymphocyte blastogenesis, and delayed cutaneous hypersensitivity were normal. This patients represents another of the growing number of distinct granulocytopathies currently being recognized which may result in increased susceptibility to infection.", "contents": "Defective polymorphonuclear leukocyte chemotaxis and bactericidal capacity in a boy with recurrent pyogenic infections. A 13-year-old boy with a history of recurrent pyogenic infections had abnormalities of polymorphonuclear leukocyte (PMN) function which probably accounted for his susceptibility to infection. PMN phagocytosis and nitroblue tetrazolium dye reduction were normal but glucose 14C oxidation was abnormally increased in resting cells. The patient's PMNs possessed decreased bactericidal activity against Staphylococcus aureus and Escherichia coli. Also documented were decreased PMN chemotactic activity and leukocyte accumulation in Rebuck skin windows. PMN random motility, PMN bone marrow reserve, PMN kinetics, lymphocyte blastogenesis, and delayed cutaneous hypersensitivity were normal. This patients represents another of the growing number of distinct granulocytopathies currently being recognized which may result in increased susceptibility to infection."}
{"id": "PMID:9620", "title": "Polynucleotides. XL. Synthesis and properties of poly 2'-azido-2'-deoxyadenylic acid.", "content": "Poly 2'-azido-2'-deoxyadenylic acid (Poly Az) was synthesized from 2'-azido-2'-deoxyadenosine diphosphate by polynucleotide phosphorylase. Poly (Az) has U.V. absorption properties similar to poly (A) and hypochromicity of 40% at 0.1 M Na+ and neutrality. CD curve also resembled to that of poly (A), but has smaller ellipticity. Titration of poly (Az) with HCl gave a transition at pH 5.5, but exact structure of the acid-form complex was not elucidated. Upon mixing with poly (U), poly (Az) forms a 1:1 and 1:2 complexes having Tm's somewhat higher than that of poly (A)- poly (U) complex in the same condition.", "contents": "Polynucleotides. XL. Synthesis and properties of poly 2'-azido-2'-deoxyadenylic acid. Poly 2'-azido-2'-deoxyadenylic acid (Poly Az) was synthesized from 2'-azido-2'-deoxyadenosine diphosphate by polynucleotide phosphorylase. Poly (Az) has U.V. absorption properties similar to poly (A) and hypochromicity of 40% at 0.1 M Na+ and neutrality. CD curve also resembled to that of poly (A), but has smaller ellipticity. Titration of poly (Az) with HCl gave a transition at pH 5.5, but exact structure of the acid-form complex was not elucidated. Upon mixing with poly (U), poly (Az) forms a 1:1 and 1:2 complexes having Tm's somewhat higher than that of poly (A)- poly (U) complex in the same condition."}
{"id": "PMID:9621", "title": "Properties of DNA ligase from uninfected and virus-infected HeLa cells.", "content": "HeLa cells contain a high M.W. form of DNA ligase which can be completely converted to a low M.W. form. Stokes radius, frictional ratio, sedimentation coefficient, molecular weight, pH dependence, and heat inactivation rate of the two forms have been studied. The major properties of the two forms of DNA ligase in HeLa cells (in particular molecular weights and pH dependence) resemble those of the \"dimer\" and \"monomer\" structures described in cultured human cells (Pedrali, G., Spadari, S., Ciarrocchi, G., Pedrini, M., Falaschi, A. (1973) Eur. J. Biochem., 39 343) . In synchronized HeLa cells, the DNA ligase shows a two fold increase during S phase and parallels the increase in the DNA synthesis rate. DNA ligase increases in parallel with viral DNA synthesis after infection of HeLa cells with vaccinia and Herpes virus but its cofactor requirements and physical properties (including the dimer leads to monomer conversion) are unchanged, suggesting that the newly formed ligase is not virus-coded.", "contents": "Properties of DNA ligase from uninfected and virus-infected HeLa cells. HeLa cells contain a high M.W. form of DNA ligase which can be completely converted to a low M.W. form. Stokes radius, frictional ratio, sedimentation coefficient, molecular weight, pH dependence, and heat inactivation rate of the two forms have been studied. The major properties of the two forms of DNA ligase in HeLa cells (in particular molecular weights and pH dependence) resemble those of the \"dimer\" and \"monomer\" structures described in cultured human cells (Pedrali, G., Spadari, S., Ciarrocchi, G., Pedrini, M., Falaschi, A. (1973) Eur. J. Biochem., 39 343) . In synchronized HeLa cells, the DNA ligase shows a two fold increase during S phase and parallels the increase in the DNA synthesis rate. DNA ligase increases in parallel with viral DNA synthesis after infection of HeLa cells with vaccinia and Herpes virus but its cofactor requirements and physical properties (including the dimer leads to monomer conversion) are unchanged, suggesting that the newly formed ligase is not virus-coded."}
{"id": "PMID:9622", "title": "Histones bind more tightly to bromodeoxyuridine-substituted DNA than to normal DNA.", "content": "Using a membrane filter assay, we have obtained results from both kinetic and competition experiments indicating that histones bind more strongly to bromodeoxyuridine-substituted DNA than to normal DNA. At 37 degrees C in our standard buffer of 0.2 M ionic strength, the rate of dissociation of histones H1, H2, and h4 from BrdU-substituted DNA is respectively 7, 4, and 2 times slower than it is from normal DNA. Competition experiments show an even greater difference between BrdU-substituted and normal DNA with respect to histone binding. The tighter binding of histones to BrdU-substituted DNA is of interest because of the known effects of BrdU on eukaryotic chromosome condensation and staining, virus induction, and the inhibition of differentiation.", "contents": "Histones bind more tightly to bromodeoxyuridine-substituted DNA than to normal DNA. Using a membrane filter assay, we have obtained results from both kinetic and competition experiments indicating that histones bind more strongly to bromodeoxyuridine-substituted DNA than to normal DNA. At 37 degrees C in our standard buffer of 0.2 M ionic strength, the rate of dissociation of histones H1, H2, and h4 from BrdU-substituted DNA is respectively 7, 4, and 2 times slower than it is from normal DNA. Competition experiments show an even greater difference between BrdU-substituted and normal DNA with respect to histone binding. The tighter binding of histones to BrdU-substituted DNA is of interest because of the known effects of BrdU on eukaryotic chromosome condensation and staining, virus induction, and the inhibition of differentiation."}
{"id": "PMID:9623", "title": "The reaction between thiols and 8-azidoadenosine derivatives.", "content": "Thiols react at room temperature in dilute solution with 8-azidoadenosine and its nucleotides to give the corresponding 8-aminoadenosine derivatives. The reaction which takes place in the dark is base-catalysed and is particularly rapid when dithiols, e.g. dithiothreitol are used.", "contents": "The reaction between thiols and 8-azidoadenosine derivatives. Thiols react at room temperature in dilute solution with 8-azidoadenosine and its nucleotides to give the corresponding 8-aminoadenosine derivatives. The reaction which takes place in the dark is base-catalysed and is particularly rapid when dithiols, e.g. dithiothreitol are used."}
{"id": "PMID:9624", "title": "Novikoff hepatoma deoxyribonucleic acid polymerase. Sensitivity of the beta-polymerase to sulfhydryl blocking agents.", "content": "Unlike other beta-class eukaryotic DNA polymerases, the enzyme purified from the Novikoff hepatoma is inhibited by both sulfhydryl blocking agents N-ethylmaleimide (NEM) and p-hydroxymercuribenzoate (pHMB). The degree of sensitivity varies depending on the enzyme purity, pH of the reaction, and the presence of sulfhydryl reducing agents. Novikoff beta-polymerase activity is unaffected by the presence of 2-mercaptoethanol (2-Me) or dithiothreitol (DTT); however, the combination of 2-mercaptoethanol and NEM or pHMB acts to reverse the inhibition of the sulfhydryl blocking agent. The reversal of inhibition involves more than just a titration of NEM with 2-mercaptoethanol since a) the combination of these two reagents actually stimulates the DNA polymerase, and b) dithiothreitol did not reverse the inhibition. Binding of the polymerase to DNA did not affect the enzyme sensitivity to NEM.", "contents": "Novikoff hepatoma deoxyribonucleic acid polymerase. Sensitivity of the beta-polymerase to sulfhydryl blocking agents. Unlike other beta-class eukaryotic DNA polymerases, the enzyme purified from the Novikoff hepatoma is inhibited by both sulfhydryl blocking agents N-ethylmaleimide (NEM) and p-hydroxymercuribenzoate (pHMB). The degree of sensitivity varies depending on the enzyme purity, pH of the reaction, and the presence of sulfhydryl reducing agents. Novikoff beta-polymerase activity is unaffected by the presence of 2-mercaptoethanol (2-Me) or dithiothreitol (DTT); however, the combination of 2-mercaptoethanol and NEM or pHMB acts to reverse the inhibition of the sulfhydryl blocking agent. The reversal of inhibition involves more than just a titration of NEM with 2-mercaptoethanol since a) the combination of these two reagents actually stimulates the DNA polymerase, and b) dithiothreitol did not reverse the inhibition. Binding of the polymerase to DNA did not affect the enzyme sensitivity to NEM."}
{"id": "PMID:9626", "title": "The relationship between beta-blockade, hyporeninaemic and hypotensive effect of two beta-blocking agents.", "content": "In two consecutive series of hypertensive patients the hypotensive effect, the hyporeninaemic effect and the blockade of cardiac beta-receptors was studied using weekly increasing doses of propranolol or atenolol. With both beta-blockers, cardiac blockade and hypotensive effect increased in a parallel fashion when the dosage was increased suggesting that the hypotensive effect is related to cardiac beta-blockade. On the other hand lack of parallelism between the hypotensive effect and the hyporeninaemic effect suggests that the hypotensive effect was not related to a major extent to the hyporeninaemic effect of the drugs in the dosage range studied here.", "contents": "The relationship between beta-blockade, hyporeninaemic and hypotensive effect of two beta-blocking agents. In two consecutive series of hypertensive patients the hypotensive effect, the hyporeninaemic effect and the blockade of cardiac beta-receptors was studied using weekly increasing doses of propranolol or atenolol. With both beta-blockers, cardiac blockade and hypotensive effect increased in a parallel fashion when the dosage was increased suggesting that the hypotensive effect is related to cardiac beta-blockade. On the other hand lack of parallelism between the hypotensive effect and the hyporeninaemic effect suggests that the hypotensive effect was not related to a major extent to the hyporeninaemic effect of the drugs in the dosage range studied here."}
{"id": "PMID:9627", "title": "Ahlquist and the development of beta-adrenoceptor antagonists.", "content": "The power and fecundity of Ahlquist's original concept of alpha- and beta-receptors can now be seen in dramatic contrast to the obfuscation and sterility of the then contemporary theory of two \"sympathins\". But when his famous paper appeared in 1948, pharmacologists apparently were not ready for the new idea. Receptor theory was perhaps too esoteric (Dale, one of the great pharmacologists of his time, studiously ignored it) and pharamacological taxonomy was virtually non-existent. The relationship of the new idea to Ehrlich's older ones, with consequent utilitarian implications, was overlooked.", "contents": "Ahlquist and the development of beta-adrenoceptor antagonists. The power and fecundity of Ahlquist's original concept of alpha- and beta-receptors can now be seen in dramatic contrast to the obfuscation and sterility of the then contemporary theory of two \"sympathins\". But when his famous paper appeared in 1948, pharmacologists apparently were not ready for the new idea. Receptor theory was perhaps too esoteric (Dale, one of the great pharmacologists of his time, studiously ignored it) and pharamacological taxonomy was virtually non-existent. The relationship of the new idea to Ehrlich's older ones, with consequent utilitarian implications, was overlooked."}
{"id": "PMID:9628", "title": "The properties of beta-adrenoceptor antagonists.", "content": "After the clinical studies with pronethalol and propranolol confirmed Black's hypothesis that drugs which block beta-adrenoceptors were of value in the treatment of patients with angina pectoris and cardiac arrhythmias, other compounds have been described which block beta-adrenoceptors. Detailed pharmacological studies with propranolol and comparison of its properties with those of other beta-adrenoceptor blocking drugs have indicated that these drugs may possess properties in addition to their effect in blocking beta-adrenoceptors. These properties have been termed intrinsic sympathomimetic activity, membrane stabilizing activity and cardioselectivity. These properties have all been described in detailed observations in laboratory animals but not to the same extent in normal man or in patients. It appears that the therapeutic effectiveness of these drugs results from their beta-adrenoceptor blocking activity and that intrinsic sympathomimetic activity and membrane stabilizing activity do not contribute to the effects of these drugs in patients, although cardioselectivity may be of value in some patients.", "contents": "The properties of beta-adrenoceptor antagonists. After the clinical studies with pronethalol and propranolol confirmed Black's hypothesis that drugs which block beta-adrenoceptors were of value in the treatment of patients with angina pectoris and cardiac arrhythmias, other compounds have been described which block beta-adrenoceptors. Detailed pharmacological studies with propranolol and comparison of its properties with those of other beta-adrenoceptor blocking drugs have indicated that these drugs may possess properties in addition to their effect in blocking beta-adrenoceptors. These properties have been termed intrinsic sympathomimetic activity, membrane stabilizing activity and cardioselectivity. These properties have all been described in detailed observations in laboratory animals but not to the same extent in normal man or in patients. It appears that the therapeutic effectiveness of these drugs results from their beta-adrenoceptor blocking activity and that intrinsic sympathomimetic activity and membrane stabilizing activity do not contribute to the effects of these drugs in patients, although cardioselectivity may be of value in some patients."}
{"id": "PMID:9629", "title": "Beta-blockade and mechanisms of disease.", "content": "In this review an attempt has been made to define the contribution of beta-antagonists to out understanding of the mechanisms of disease. It is concluded that beta-antagonists, and propranolol in particular, have clarified mechanisms in angina pectoris, cardiac arrhythmias and some aspects of essential hypertension as well as hypertrophic obstructive cardiomyopathy. The study of beta-antagonists in anxiety states shows that they can help to define the somatic component but give no clue as to central mechanisms involved. There is no substantial evidence that beta-antogonists are of value in the psychoses and these negative findings suggest that disturbances of brain catecholamines contribute little to the pathogenesis of these conditions.", "contents": "Beta-blockade and mechanisms of disease. In this review an attempt has been made to define the contribution of beta-antagonists to out understanding of the mechanisms of disease. It is concluded that beta-antagonists, and propranolol in particular, have clarified mechanisms in angina pectoris, cardiac arrhythmias and some aspects of essential hypertension as well as hypertrophic obstructive cardiomyopathy. The study of beta-antagonists in anxiety states shows that they can help to define the somatic component but give no clue as to central mechanisms involved. There is no substantial evidence that beta-antogonists are of value in the psychoses and these negative findings suggest that disturbances of brain catecholamines contribute little to the pathogenesis of these conditions."}
{"id": "PMID:9630", "title": "Mechanism of action of beta-blocking drugs in angina pectoris: a review.", "content": "The effect of beta-blockers in improving exercise tolerance in angina pectoris can be accounted for by the reduction in heart rate and arterial pressure than they produce. The failure of a few patients to respond despite reduction in heart rate and the failure of those who do respond to obtain the full expected benefit suggests that beta-blockade has some action that offsets in while or in part the advantage gained from reduction in heart rate and pressure. This action might include an increase in left ventricular size with consequent increase in work, or an increase in left ventricular diastolic pressure with resultant impairment of blood flow to the inner layers of the myocardium.", "contents": "Mechanism of action of beta-blocking drugs in angina pectoris: a review. The effect of beta-blockers in improving exercise tolerance in angina pectoris can be accounted for by the reduction in heart rate and arterial pressure than they produce. The failure of a few patients to respond despite reduction in heart rate and the failure of those who do respond to obtain the full expected benefit suggests that beta-blockade has some action that offsets in while or in part the advantage gained from reduction in heart rate and pressure. This action might include an increase in left ventricular size with consequent increase in work, or an increase in left ventricular diastolic pressure with resultant impairment of blood flow to the inner layers of the myocardium."}
{"id": "PMID:9631", "title": "Effect of propranolol on mortality in patients with angina.", "content": "Two hundred and seventeen patients from general practice suffering from angina pectoris were studied over a three year period; 91 patients had beta-blocker treatment, the other 126 did not. The two groups were comparable for age, sex, blood pressure and length of history of angina. The frequency of infarction and mortality from infarction in the two groups was compared. The annual infarct rate in the 126 patients not treated with beta-blockers is shown to be more than three times the rate in the 91 patients treated by beta-blockers. The annual death rate from myocardial infarction is almost four times greater in the group not treated by beta-blockers compared with the beta-blocked group. It is concluded that this provides further evidence that treatment which includes beta-blockade in patients suffering from ischamic heart disease reduces the risk of myocardial infarction and death.", "contents": "Effect of propranolol on mortality in patients with angina. Two hundred and seventeen patients from general practice suffering from angina pectoris were studied over a three year period; 91 patients had beta-blocker treatment, the other 126 did not. The two groups were comparable for age, sex, blood pressure and length of history of angina. The frequency of infarction and mortality from infarction in the two groups was compared. The annual infarct rate in the 126 patients not treated with beta-blockers is shown to be more than three times the rate in the 91 patients treated by beta-blockers. The annual death rate from myocardial infarction is almost four times greater in the group not treated by beta-blockers compared with the beta-blocked group. It is concluded that this provides further evidence that treatment which includes beta-blockade in patients suffering from ischamic heart disease reduces the risk of myocardial infarction and death."}
{"id": "PMID:9632", "title": "Adverse reactions to beta-blocking drugs: a review.", "content": "Adverse reactions may occur as a predictable or unpredictable drug-induced illness can be reduced if the awareness of the prescribing doctor of clinically relevant drug and patient factors, which affect the response to the drug, can be increased. However, unexpected and unpredictable adverse reactions, sometimes reported as a single case in an anecdotal case report, are more difficult to evaluate and explain. Beta-blocking agents such as propranolol, oxprenolol and practolol have been asssociated with numerous adverse reactions. The influence of drug factors, such as range of action, absorption, metabolism, excretion, interactions, and patient factors such as disease states, idiosyncrasy, and personality are discussed.", "contents": "Adverse reactions to beta-blocking drugs: a review. Adverse reactions may occur as a predictable or unpredictable drug-induced illness can be reduced if the awareness of the prescribing doctor of clinically relevant drug and patient factors, which affect the response to the drug, can be increased. However, unexpected and unpredictable adverse reactions, sometimes reported as a single case in an anecdotal case report, are more difficult to evaluate and explain. Beta-blocking agents such as propranolol, oxprenolol and practolol have been asssociated with numerous adverse reactions. The influence of drug factors, such as range of action, absorption, metabolism, excretion, interactions, and patient factors such as disease states, idiosyncrasy, and personality are discussed."}
{"id": "PMID:9633", "title": "Discovery of the hypotensive effect of propranolol.", "content": "Following the observation that pronethalol lowered the blood pressure a similar effect was demonstrated with propranolol. Over a period of years propranolol was demonstrated to produce a fall in blood pressure comparable with other potent drugs with the advantage of good control of the supine blood pressure and with the absence of postural and exercise hypotension. These observations were slow to be accepted, as besides a novel mode of action, most attempts to repeat the work failed to pay enough attention to adequate dosage.", "contents": "Discovery of the hypotensive effect of propranolol. Following the observation that pronethalol lowered the blood pressure a similar effect was demonstrated with propranolol. Over a period of years propranolol was demonstrated to produce a fall in blood pressure comparable with other potent drugs with the advantage of good control of the supine blood pressure and with the absence of postural and exercise hypotension. These observations were slow to be accepted, as besides a novel mode of action, most attempts to repeat the work failed to pay enough attention to adequate dosage."}
{"id": "PMID:9634", "title": "The use of propranolol in hypertension: a review.", "content": "A review if given of the use of propranolol in hypertension emphasizing the importance of the studies by Prichard and Gillam in 1964 and 1969. The current use of propranolol in hypertension as regards dosage, dose intervals and starting doses is also outlined. Moreover, the combined treatment with propranolol and vasodilators is briefly described, as are attempts to make predictions of the therapeutic response by studying various haemodynamic and laboratory parameters. Finally, an attempt is made to assess the future role of propranolol in the treatment of hypertension in comparison with other antihypertensive drugs.", "contents": "The use of propranolol in hypertension: a review. A review if given of the use of propranolol in hypertension emphasizing the importance of the studies by Prichard and Gillam in 1964 and 1969. The current use of propranolol in hypertension as regards dosage, dose intervals and starting doses is also outlined. Moreover, the combined treatment with propranolol and vasodilators is briefly described, as are attempts to make predictions of the therapeutic response by studying various haemodynamic and laboratory parameters. Finally, an attempt is made to assess the future role of propranolol in the treatment of hypertension in comparison with other antihypertensive drugs."}
{"id": "PMID:9635", "title": "Indications for beta-adrenoceptor blocking drugs in hypertension.", "content": "The past 10 years have firmly established the role of beta-adrenoceptor blocking agents in the treatment of hypertension. They have been shown to lower systolic and diastolic blood pressure in the lying and standing position in mild, moderate and severe hypertension. Precise indications for beta-blockade have not yet been completely defined. Some authorities regard them as the drug of first choice in the management of most grades of idiopathic hypertension. There are in addition certain situations where beta-blockade seems especially suitable. These include the presence of associated coronary heart disease manifest either as angina pectoris or dysrhythmia. These agents can be introduced when side effects from other drugs are severe or intolerable and are valuable in the management of hypertensive young males since beta-blocking drugs do not interfere with sexual function. Compared with normotensive subjects 'stress' has been shown to produce excessive rise of blood pressure in those with labile or sustained idiopathic hypertension. After therapy with beta-blocking agents the rise in blood pressure after 'stress' is reduced. If labile and/or mild hypertension are the precursors of subsequently more severe sustained hypertension, then long term beta-blockade may help to control this response.", "contents": "Indications for beta-adrenoceptor blocking drugs in hypertension. The past 10 years have firmly established the role of beta-adrenoceptor blocking agents in the treatment of hypertension. They have been shown to lower systolic and diastolic blood pressure in the lying and standing position in mild, moderate and severe hypertension. Precise indications for beta-blockade have not yet been completely defined. Some authorities regard them as the drug of first choice in the management of most grades of idiopathic hypertension. There are in addition certain situations where beta-blockade seems especially suitable. These include the presence of associated coronary heart disease manifest either as angina pectoris or dysrhythmia. These agents can be introduced when side effects from other drugs are severe or intolerable and are valuable in the management of hypertensive young males since beta-blocking drugs do not interfere with sexual function. Compared with normotensive subjects 'stress' has been shown to produce excessive rise of blood pressure in those with labile or sustained idiopathic hypertension. After therapy with beta-blocking agents the rise in blood pressure after 'stress' is reduced. If labile and/or mild hypertension are the precursors of subsequently more severe sustained hypertension, then long term beta-blockade may help to control this response."}
{"id": "PMID:9636", "title": "Flurazepam ('Dalmane') in the treatment of insomnia in patients with respiratory disorders.", "content": "The effects on subjective aspects of sleep of flurazepam 15 mg and amylobarbitone sodium 100 mg were compared in insomniac patients with chest disease. A double-blind technique was used. The results indicate a significant superiority of flurazepam over the other drug.", "contents": "Flurazepam ('Dalmane') in the treatment of insomnia in patients with respiratory disorders. The effects on subjective aspects of sleep of flurazepam 15 mg and amylobarbitone sodium 100 mg were compared in insomniac patients with chest disease. A double-blind technique was used. The results indicate a significant superiority of flurazepam over the other drug."}
{"id": "PMID:9639", "title": "Implications of cross inhibitory interactions of potential mediators of hormone and neurotransmitter action.", "content": "Mediators of hormone and neurotransmitter action may exert negative control on the accumulation of one another (adenosine 3':5'-cyclic monophosphate, or conversely). A model in which one agonist stimulates the formation of two mediators which inhibit each other's accumulation has been simulated. Three types of agonist-receptor interaction, five mechanisms of inhibition, and three types of basal activity have been considered which lead to a set of 45 descriptions of the general cross inhibition model. For these submodels, pattern of the relation of agonist to mediator concentrations at steady state conditions have been defined. Some patterns are complex with mediator curves exhibiting extrema, one a maximum and the other a minimum. The complexity of the pattern depends on the submodel and on the degree of asymmetry between the parameters of each of the mediator pathways (e.g.,affinities for the agonist, strength of the inhibitions, etc.). This simple model can thus account for complex experimental results without requiring the postulation of elaborate molecular models of agonist-receptor interaction. The simulations presented emphasize the necessity of investigating a wide range of agonist concentrations.", "contents": "Implications of cross inhibitory interactions of potential mediators of hormone and neurotransmitter action. Mediators of hormone and neurotransmitter action may exert negative control on the accumulation of one another (adenosine 3':5'-cyclic monophosphate, or conversely). A model in which one agonist stimulates the formation of two mediators which inhibit each other's accumulation has been simulated. Three types of agonist-receptor interaction, five mechanisms of inhibition, and three types of basal activity have been considered which lead to a set of 45 descriptions of the general cross inhibition model. For these submodels, pattern of the relation of agonist to mediator concentrations at steady state conditions have been defined. Some patterns are complex with mediator curves exhibiting extrema, one a maximum and the other a minimum. The complexity of the pattern depends on the submodel and on the degree of asymmetry between the parameters of each of the mediator pathways (e.g.,affinities for the agonist, strength of the inhibitions, etc.). This simple model can thus account for complex experimental results without requiring the postulation of elaborate molecular models of agonist-receptor interaction. The simulations presented emphasize the necessity of investigating a wide range of agonist concentrations."}
{"id": "PMID:9640", "title": "Supersaturation in sickle cell hemoglobin solutions.", "content": "The kinetic inhibition of the gelation of hemoglobin S is compared to the change in hemoglobin S soulbility, when the solubility is altered by carbon monoxide, pH, or urea. By means of a new technique, the delay time and the extent of gelation are measured on the same sample. They delay time, td, is found to be proportional to a high power (30-40) of the hemoglobin S solubility. Togehter with the previously reported concentration dependence, this result demonstrates that the rate is proportional to a high power of the supersaturation, S, defined as the ratio of the total hemoglobin S concentration to the equilibrium solubility. The results obey the supersaturation equation td-1 = gammaSn, where gamma is an empirical constant (about 10(-7) sec-1) and n is about 35. The supersaturation equation can successfully account for observations on the kinetics of cell sickling and is therefore used to estimate the increase in the delay time for sickling necessary to produce significant clinical benefit to patients with sickle cell disease.", "contents": "Supersaturation in sickle cell hemoglobin solutions. The kinetic inhibition of the gelation of hemoglobin S is compared to the change in hemoglobin S soulbility, when the solubility is altered by carbon monoxide, pH, or urea. By means of a new technique, the delay time and the extent of gelation are measured on the same sample. They delay time, td, is found to be proportional to a high power (30-40) of the hemoglobin S solubility. Togehter with the previously reported concentration dependence, this result demonstrates that the rate is proportional to a high power of the supersaturation, S, defined as the ratio of the total hemoglobin S concentration to the equilibrium solubility. The results obey the supersaturation equation td-1 = gammaSn, where gamma is an empirical constant (about 10(-7) sec-1) and n is about 35. The supersaturation equation can successfully account for observations on the kinetics of cell sickling and is therefore used to estimate the increase in the delay time for sickling necessary to produce significant clinical benefit to patients with sickle cell disease."}
{"id": "PMID:9641", "title": "Mechanism of uncoupling in mitochondria: uncouplers as ionophores for cycling cations and protons.", "content": "Classical uncouplers such as 2,4-dinitrophenol have been shown to be ionophores with the capability for transporting monovalent or divalent cations with equal efficiency. The conditions appropriate for the maximal expression of this ionophoric capability have been explored. Two critical factors are the polarity of the organic phase and the pH of the aqueous phase that is equilibrated with the organic phase. The demonstrated cationic ionophoric capability of uncouplers, taken in conjunction with the known ability of uncouplers to cycle protons across a membrane phase, provides the experimental basis for the thesis that uncoupling of electron flow from ATP synthesis via classical uncouplers involves the substitution of one coupled process by another. Uncoupling thus reduces to the replacement of one driven reaction (ATP synthesis) by the driven reaction (cyclical transport) mediated by the uncoupler.", "contents": "Mechanism of uncoupling in mitochondria: uncouplers as ionophores for cycling cations and protons. Classical uncouplers such as 2,4-dinitrophenol have been shown to be ionophores with the capability for transporting monovalent or divalent cations with equal efficiency. The conditions appropriate for the maximal expression of this ionophoric capability have been explored. Two critical factors are the polarity of the organic phase and the pH of the aqueous phase that is equilibrated with the organic phase. The demonstrated cationic ionophoric capability of uncouplers, taken in conjunction with the known ability of uncouplers to cycle protons across a membrane phase, provides the experimental basis for the thesis that uncoupling of electron flow from ATP synthesis via classical uncouplers involves the substitution of one coupled process by another. Uncoupling thus reduces to the replacement of one driven reaction (ATP synthesis) by the driven reaction (cyclical transport) mediated by the uncoupler."}
{"id": "PMID:9642", "title": "Suppression of lytic effect of beta lactams on Escherichia coli and other bacteria.", "content": "Growth of E. coli at pH 5 protected the bacteria against the lytic effect of beta lactam antibiotics typically observed when the cells are grown at pH 7 or 7.5, i.e., the pH values routinely used in laboratory experiments. In contrast, the typical effects of beta lactam antibiotics on cellular shape and elongation and cell division appeared to be similar in cultures grown under neutral and acid pH conditions. The pH-dependent antibiotic tolerance can also be demonstrated with pneumococci, staphylococci, streptococci, and Bacillus subtilis. We suggest that the mechanism of the pH-dependent antibiotic tolerance may involve either the production of a more stable plasma membrane or the suppression of the activity of a murein hydrolase(s) that catalyzes the antibiotic-induced lysis; at least a fraction of these enzyme molecules may be localized at the cell surface and be accessible to experimental manipulation.", "contents": "Suppression of lytic effect of beta lactams on Escherichia coli and other bacteria. Growth of E. coli at pH 5 protected the bacteria against the lytic effect of beta lactam antibiotics typically observed when the cells are grown at pH 7 or 7.5, i.e., the pH values routinely used in laboratory experiments. In contrast, the typical effects of beta lactam antibiotics on cellular shape and elongation and cell division appeared to be similar in cultures grown under neutral and acid pH conditions. The pH-dependent antibiotic tolerance can also be demonstrated with pneumococci, staphylococci, streptococci, and Bacillus subtilis. We suggest that the mechanism of the pH-dependent antibiotic tolerance may involve either the production of a more stable plasma membrane or the suppression of the activity of a murein hydrolase(s) that catalyzes the antibiotic-induced lysis; at least a fraction of these enzyme molecules may be localized at the cell surface and be accessible to experimental manipulation."}
{"id": "PMID:9643", "title": "Bandage-backfall reaction: occurs in infancy, hypothalamic damage, and catalepsy.", "content": "In cataleptic clinging, produced either by catecholamine-blocking drugs or lateral hypothalamic damage in adult cats, rats, or monkeys, bandaging the face and neck causes the head to fall backwards. Early in development, a similar reaction can be seen in normal undrugged infants.", "contents": "Bandage-backfall reaction: occurs in infancy, hypothalamic damage, and catalepsy. In cataleptic clinging, produced either by catecholamine-blocking drugs or lateral hypothalamic damage in adult cats, rats, or monkeys, bandaging the face and neck causes the head to fall backwards. Early in development, a similar reaction can be seen in normal undrugged infants."}
{"id": "PMID:9646", "title": "Physiological effects of the plasminolytic derivatives of fibrinogen.", "content": "The macromolecular breakdown products of fibrinogen are known mainly for their inhibitory effect on the clotting of fibrinogen by thrombin. This inhibitory effect is due to interference with both the proteolytic action of thrombin and the polymerization of the fibrin monomers. However, the action of these products is not limited to these effects. They can on the one hand inhibit the consumption of Factors II and XIII and promote the inactivation of Factor VIII by thrombin. On the other hand, they can potentiate the activation of prothrombin in purified systems via the intrinsic pathway. The incidental observation was also made that Factor IXa and or Factor Xa inactivate Factor VIII. As substrates of both thrombin and plasmin the large fragments protect these two enzymes from spontaneous inactivation, while at the same time they inhibit their respective proteolytic activities. Contradictory results were obtained regarding their effect on platelets. The micromolecular (dialyzable) breakdown products prolong the thrombin, prothrombin, and partial thromboplastin times of plasma and retard the generation of the intrinsic prothrombin activator. They can also potentiate the effects of biologically active peptides and amines on the smooth muscles and on vascular permeability.", "contents": "Physiological effects of the plasminolytic derivatives of fibrinogen. The macromolecular breakdown products of fibrinogen are known mainly for their inhibitory effect on the clotting of fibrinogen by thrombin. This inhibitory effect is due to interference with both the proteolytic action of thrombin and the polymerization of the fibrin monomers. However, the action of these products is not limited to these effects. They can on the one hand inhibit the consumption of Factors II and XIII and promote the inactivation of Factor VIII by thrombin. On the other hand, they can potentiate the activation of prothrombin in purified systems via the intrinsic pathway. The incidental observation was also made that Factor IXa and or Factor Xa inactivate Factor VIII. As substrates of both thrombin and plasmin the large fragments protect these two enzymes from spontaneous inactivation, while at the same time they inhibit their respective proteolytic activities. Contradictory results were obtained regarding their effect on platelets. The micromolecular (dialyzable) breakdown products prolong the thrombin, prothrombin, and partial thromboplastin times of plasma and retard the generation of the intrinsic prothrombin activator. They can also potentiate the effects of biologically active peptides and amines on the smooth muscles and on vascular permeability."}
{"id": "PMID:9648", "title": "Bromazepam versus diazepam in psychoneurotic inpatients.", "content": "A double blind between-groups trial was carried out to compare the effectiveness of the new benzodiazepine compound, bromazepam, (Lexotan, Ro 5-3350) as an anti-anxiety compound with that of diazepan. The fifty-eight psychoneurotic inpatients admitted to the trial were divided into two groups, \"obsessives\" and \"neurotics\", in order to assess any specific action of the drug. Assessment was made by means of B.P.R.S. of Overall and Gorham, R.S.A.S. of Hamilton, P.R.S. of Wittenborn and I.M.P.S. of Lorr. The results showed that bromazepam has a general therapeutic effectiveness (though not always as great as that of diazepam) as an anti-anxiety agent, while no difference in the effects of the two drugs was found between the two psychopathologic groups; with both treatments the \"obsessives\" responded less than the \"neurotics\". Detailed evaluation of the individual items of the I.M.P.S. showed that bromazepam is likely to exert a disinhibiting or \"activating\" action, unlike most other benzodiazepines in clinical use.", "contents": "Bromazepam versus diazepam in psychoneurotic inpatients. A double blind between-groups trial was carried out to compare the effectiveness of the new benzodiazepine compound, bromazepam, (Lexotan, Ro 5-3350) as an anti-anxiety compound with that of diazepan. The fifty-eight psychoneurotic inpatients admitted to the trial were divided into two groups, \"obsessives\" and \"neurotics\", in order to assess any specific action of the drug. Assessment was made by means of B.P.R.S. of Overall and Gorham, R.S.A.S. of Hamilton, P.R.S. of Wittenborn and I.M.P.S. of Lorr. The results showed that bromazepam has a general therapeutic effectiveness (though not always as great as that of diazepam) as an anti-anxiety agent, while no difference in the effects of the two drugs was found between the two psychopathologic groups; with both treatments the \"obsessives\" responded less than the \"neurotics\". Detailed evaluation of the individual items of the I.M.P.S. showed that bromazepam is likely to exert a disinhibiting or \"activating\" action, unlike most other benzodiazepines in clinical use."}
{"id": "PMID:9649", "title": "[Practice and further development of the AMP-system (a report about a symposion and a seminar) (author's transl)].", "content": "During two days in November 1974 TV-tapes of psychiatric interviews were demonstrated and the psychopathology was documented on AMP-record sheet 3. It was a purpose of the discussion to get stimulation for the improvement of the AMP-manual and to decrease the interrater-variance. It was only the first tape which was not followed by a discussion. This film was presented a second time at the end of the seminar in order to examine the training effects. Both record-sheets were compared with each other. Generally the variance decreased. The discussion as to an improvement of the AMP-manual lead to the following suggestions: In defining a psychopathological item it is important to differentiate more precisely between the patient's subjective experience and his behaviour, to find better criteria concerning the rating of different intensities and to improve discrimination between singular items. Furthermore the logic of documentation procedure should be unequivocal and more practical. Following the seminar there was a symposion discussion more general and some specific methodological problems of the further development of the AMP-system. Finally study groups were formed to elaborate on the topics \"AMP-manual\", \"rater-training\", \"social data\" and \"electronic data processing\".", "contents": "[Practice and further development of the AMP-system (a report about a symposion and a seminar) (author's transl)]. During two days in November 1974 TV-tapes of psychiatric interviews were demonstrated and the psychopathology was documented on AMP-record sheet 3. It was a purpose of the discussion to get stimulation for the improvement of the AMP-manual and to decrease the interrater-variance. It was only the first tape which was not followed by a discussion. This film was presented a second time at the end of the seminar in order to examine the training effects. Both record-sheets were compared with each other. Generally the variance decreased. The discussion as to an improvement of the AMP-manual lead to the following suggestions: In defining a psychopathological item it is important to differentiate more precisely between the patient's subjective experience and his behaviour, to find better criteria concerning the rating of different intensities and to improve discrimination between singular items. Furthermore the logic of documentation procedure should be unequivocal and more practical. Following the seminar there was a symposion discussion more general and some specific methodological problems of the further development of the AMP-system. Finally study groups were formed to elaborate on the topics \"AMP-manual\", \"rater-training\", \"social data\" and \"electronic data processing\"."}
{"id": "PMID:9651", "title": "[Problems of prevention, registration and evaluation of post-vaccination neurogenic lesions in children from clinical and legal viewpoints. II. Problems in the evaluation of neurogenic post-vaccination lesions in childhood].", "content": "On the view of neurologist the authors describe the suppositions and the special problems of diagnostic and the importance of clinical and paraclinical findings for medical vaccination reports. They examined 13 patients with neurological cerebral defects after triple vaccination (DPT).", "contents": "[Problems of prevention, registration and evaluation of post-vaccination neurogenic lesions in children from clinical and legal viewpoints. II. Problems in the evaluation of neurogenic post-vaccination lesions in childhood]. On the view of neurologist the authors describe the suppositions and the special problems of diagnostic and the importance of clinical and paraclinical findings for medical vaccination reports. They examined 13 patients with neurological cerebral defects after triple vaccination (DPT)."}
{"id": "PMID:9652", "title": "Effects of humoral modulators and naloxone on morphine-induced changes in the spontaneous locomotor activity of the rat.", "content": "The s.c. administration of 20 mg/kg of morphine-HCl produced a decrease in the spontaneous locomotor activity (SLMA) of rats. The decrease in SLMA was significantly antagonized by p-chlorophenylalanine (p-CPA). When rats pretreated with p-CPA were given 5-hydroxytryptophan before morphine injection, the marked sedative response to morphine was restored, suggesting that the morphine-induced decrease in SLMA of rats may depend on the release of 5-hydroxytryptamine by morphine. By contrast, the s.c. administration of 5 mg/kg of morphine-HCl produced a significant increase in SLMA of rats. The magnitude of the increase was reduced by atropine, scopolamine or alpha-methyl-p-tyrosine. It appears that both adrenergic and cholinergic mechanisms participate in the increase in SLMA of rats induced by morphine. Both the increase in SLMA produced by 5 mg/kg of morphine and the decrease in SLMA induced by 20 mg/kg of morphine were completely antagonized by the s.c. administration of naloxone-HCl, 0.0625 and 0.25 mg/kg, respectively. Thus, it appears that the receptor with which morphine interacts to produce stimulation is chemically identical with or very similar to the receptor with which morphine combines to induce depression. The former receptors, however, are likely to be located on different neurons from the latter.", "contents": "Effects of humoral modulators and naloxone on morphine-induced changes in the spontaneous locomotor activity of the rat. The s.c. administration of 20 mg/kg of morphine-HCl produced a decrease in the spontaneous locomotor activity (SLMA) of rats. The decrease in SLMA was significantly antagonized by p-chlorophenylalanine (p-CPA). When rats pretreated with p-CPA were given 5-hydroxytryptophan before morphine injection, the marked sedative response to morphine was restored, suggesting that the morphine-induced decrease in SLMA of rats may depend on the release of 5-hydroxytryptamine by morphine. By contrast, the s.c. administration of 5 mg/kg of morphine-HCl produced a significant increase in SLMA of rats. The magnitude of the increase was reduced by atropine, scopolamine or alpha-methyl-p-tyrosine. It appears that both adrenergic and cholinergic mechanisms participate in the increase in SLMA of rats induced by morphine. Both the increase in SLMA produced by 5 mg/kg of morphine and the decrease in SLMA induced by 20 mg/kg of morphine were completely antagonized by the s.c. administration of naloxone-HCl, 0.0625 and 0.25 mg/kg, respectively. Thus, it appears that the receptor with which morphine interacts to produce stimulation is chemically identical with or very similar to the receptor with which morphine combines to induce depression. The former receptors, however, are likely to be located on different neurons from the latter."}
{"id": "PMID:9653", "title": "Treatment of phenothiazine-induced dyskinesia.", "content": "Previous experience indicated the possibility that a serotonin antagonist substance, was effective in relieving dyskinesia as a reaction to phenothiazine antipsychotic drugs. Since the substances used in the original observations did not become available on the United States market, a compound known to be a serotonin antagonist, cyproheptadine, which was readily available and safe, was used to treat three patients who had phenothiazine-induced dyskinesia. In these patients, cyproheptadine was definitely effective in relieving the dyskinesia over an extended period of time. Further controlled studies are required to confirm this report.", "contents": "Treatment of phenothiazine-induced dyskinesia. Previous experience indicated the possibility that a serotonin antagonist substance, was effective in relieving dyskinesia as a reaction to phenothiazine antipsychotic drugs. Since the substances used in the original observations did not become available on the United States market, a compound known to be a serotonin antagonist, cyproheptadine, which was readily available and safe, was used to treat three patients who had phenothiazine-induced dyskinesia. In these patients, cyproheptadine was definitely effective in relieving the dyskinesia over an extended period of time. Further controlled studies are required to confirm this report."}
{"id": "PMID:9654", "title": "Narcotic blockade, length of addiction and persistence of etonitazene consumption in rats.", "content": "Rats were given daily trials to determine relative preference for an opiate (etonitazene, ETZ) or for water. Animals with a greater history of previous drug exposure developed ETZ preferences more rapidly than did relatively drug-naive animals. Pretreatment with adequate blocking doses of naloxone reduced drug intake to near zero in most subjects. However, animals with the greatest history of prior addiction continued to drink large quantities of ETZ, despite pretreatment with relatively large doses of naloxone. These results can be explained by assuming that stimuli associated with the reinforcing properties of the opioid solution become strong conditioned reinforcers, capable of maintaining responding for long periods of time despite blockade of the reinforcement properties of the drug.", "contents": "Narcotic blockade, length of addiction and persistence of etonitazene consumption in rats. Rats were given daily trials to determine relative preference for an opiate (etonitazene, ETZ) or for water. Animals with a greater history of previous drug exposure developed ETZ preferences more rapidly than did relatively drug-naive animals. Pretreatment with adequate blocking doses of naloxone reduced drug intake to near zero in most subjects. However, animals with the greatest history of prior addiction continued to drink large quantities of ETZ, despite pretreatment with relatively large doses of naloxone. These results can be explained by assuming that stimuli associated with the reinforcing properties of the opioid solution become strong conditioned reinforcers, capable of maintaining responding for long periods of time despite blockade of the reinforcement properties of the drug."}
{"id": "PMID:9655", "title": "On the supersensitivity of dopamine receptors, induced by neuroleptics.", "content": "Different neuroleptics caused dopamine receptor blockade (antagonism against methylphenidate-induced compulsive gnawing) for varying lengths of time. When the receptor blockade had expired, supersensitivity to dopamine agonists (occurrence of apomorphine-induced compulsive gnawing and enhancement of methylphenidate-induced gnawing) developed and persisted for varying periods of time. The degree and duration of supersensitivity was related to the degree and duration of the preceding receptor blockade. Inhibition of catecholamine or 5-HT synthesis had no influence on development of supersensitivity. Stimulation with a dopamine agonist, apomorphine, during the period of the development of supersensitivity did not modify the enhanced receptor supersensitivity. A cholinergic-dopaminergic balance was shown to be involved in the manifestation of compulsive behavior during the supersensitivity phase. Tolerance to the dopamine antagonistic effect of a neuroleptic also developed after a single neuroleptic treatment, most likely due to increased sensitivity of the receptors for the dopamine agonist. It is concluded, that the dopamine receptor blockade induced by a single dose of a neuroleptic agent is a dynamic phenomenon which in the course of time is replaced by an increased sensitivity of the receptors to dopamine agonists. Noradrenergic or 5-HT neuron systems do not seem to be involved in the neuroleptic-induced supersensitivity, whereas a dopaminergic-cholinergic balance is operative in the supersensitivity situation.", "contents": "On the supersensitivity of dopamine receptors, induced by neuroleptics. Different neuroleptics caused dopamine receptor blockade (antagonism against methylphenidate-induced compulsive gnawing) for varying lengths of time. When the receptor blockade had expired, supersensitivity to dopamine agonists (occurrence of apomorphine-induced compulsive gnawing and enhancement of methylphenidate-induced gnawing) developed and persisted for varying periods of time. The degree and duration of supersensitivity was related to the degree and duration of the preceding receptor blockade. Inhibition of catecholamine or 5-HT synthesis had no influence on development of supersensitivity. Stimulation with a dopamine agonist, apomorphine, during the period of the development of supersensitivity did not modify the enhanced receptor supersensitivity. A cholinergic-dopaminergic balance was shown to be involved in the manifestation of compulsive behavior during the supersensitivity phase. Tolerance to the dopamine antagonistic effect of a neuroleptic also developed after a single neuroleptic treatment, most likely due to increased sensitivity of the receptors for the dopamine agonist. It is concluded, that the dopamine receptor blockade induced by a single dose of a neuroleptic agent is a dynamic phenomenon which in the course of time is replaced by an increased sensitivity of the receptors to dopamine agonists. Noradrenergic or 5-HT neuron systems do not seem to be involved in the neuroleptic-induced supersensitivity, whereas a dopaminergic-cholinergic balance is operative in the supersensitivity situation."}
{"id": "PMID:9656", "title": "The demonstration of a change in adrenergic receptor sensitivity in the central nervous system of mice after withdrawal from long-term treatment with haloperidol.", "content": "Mice, administered haloperidol (3 mg/kg/d) in their drinking water for 21 days, displayed, 4 days after cessation of the haloperidol-treatment, marked locomotor stimulation to clonidine (100 or 500 mug/kg) which lasted for about 6 h. 25 mug clonidine/kg was inactive. Premedication with FLA-63 (25 mg/kg) blocked the difference in stimulation after clonidine between the haloperidol- and vehicle-treated animals, but locomotor activity was still present in both groups. Haloperidol-treated animals displayed a supersensitive response to dexamphetamine. The difference in stimulation produced by dexamphetamine in the two groups was completely blocked by phenoxybenzamine (2.5 mg/kg), phentolamine (10 mg/kg), which drugs did not, however, block the locomotor stimulation produced by dexamphetamine in vehicle-treated animals. Pimozide (3 mg/kg) blocked all locomotor stimulation produced by dexamphetamine in both vehicle- and haloperidol-treated groups, while 1 mg/kg completely blocked the dexamphetamine response in vehicle-treated animals but not in haloperidol-treated animals. FLA-63 (25 mg/kg) blocked the difference in response between the haloperidol- and vehicle-treated groups to dexamphetamine, but did not antagonise the stimulation in the vehicle-treated animals. The data suggest that long-term haloperidol treatment leads to the development of \"supersensitive\" adrenergic receptors in the central nervous system, which, appropriately stimulated, effect an increase in locomotor activity. Moreover, the results indicate that a large component of the supersensitive response to dexamphetamine observed after long-term haloperidol-treatment is due to adrenergic receptor supersensitivity. However, the dopamine receptor (which was shown to be supersensitive to apomorphine) is of fundamental importance because phenoxybenzamine and phentolamine, while blocking the supersensitive response to dexamphetamine, failed to block the response to dexamphetamine in vehicle-treated animals, which was, however, blocked by pimozide.", "contents": "The demonstration of a change in adrenergic receptor sensitivity in the central nervous system of mice after withdrawal from long-term treatment with haloperidol. Mice, administered haloperidol (3 mg/kg/d) in their drinking water for 21 days, displayed, 4 days after cessation of the haloperidol-treatment, marked locomotor stimulation to clonidine (100 or 500 mug/kg) which lasted for about 6 h. 25 mug clonidine/kg was inactive. Premedication with FLA-63 (25 mg/kg) blocked the difference in stimulation after clonidine between the haloperidol- and vehicle-treated animals, but locomotor activity was still present in both groups. Haloperidol-treated animals displayed a supersensitive response to dexamphetamine. The difference in stimulation produced by dexamphetamine in the two groups was completely blocked by phenoxybenzamine (2.5 mg/kg), phentolamine (10 mg/kg), which drugs did not, however, block the locomotor stimulation produced by dexamphetamine in vehicle-treated animals. Pimozide (3 mg/kg) blocked all locomotor stimulation produced by dexamphetamine in both vehicle- and haloperidol-treated groups, while 1 mg/kg completely blocked the dexamphetamine response in vehicle-treated animals but not in haloperidol-treated animals. FLA-63 (25 mg/kg) blocked the difference in response between the haloperidol- and vehicle-treated groups to dexamphetamine, but did not antagonise the stimulation in the vehicle-treated animals. The data suggest that long-term haloperidol treatment leads to the development of \"supersensitive\" adrenergic receptors in the central nervous system, which, appropriately stimulated, effect an increase in locomotor activity. Moreover, the results indicate that a large component of the supersensitive response to dexamphetamine observed after long-term haloperidol-treatment is due to adrenergic receptor supersensitivity. However, the dopamine receptor (which was shown to be supersensitive to apomorphine) is of fundamental importance because phenoxybenzamine and phentolamine, while blocking the supersensitive response to dexamphetamine, failed to block the response to dexamphetamine in vehicle-treated animals, which was, however, blocked by pimozide."}
{"id": "PMID:9657", "title": "Changes in brain norepinephrine associated with sensitization to d-amphetamine.", "content": "Pretreatment of B6AF1/J mice with d-amphetamine HCl 10 mg/kg, twice daily for 5 days, produced a 4-fold increase in the running response to a test dose of 5 mg/kg amphetamine. Amphetamine pretreatment decreased whole-brain norepinephrine levels to 50% of control values and whole-brain dopamine to 85%. The test dose of 5 mg/kg amphetamine lowered whole brain norepinephrine levels of control mice from 0.50 mug/g to 0.28 mug/g in 2 h. In amphetamine-pretreated mice, this injection caused an increase in whole-brain norepinephrine levels from 0.22 mug/g to 0.55 mug/g at 30 min, followed by a decrease to 0.22 mug/g at 60 min. No change in whole brain dopamine levels was observed in either group. Amphetamine sensitization and norepinephrine depletion were still evident 25 days after pretreatment. No cross sensitization to morphine or cocaine was observed. Reserpine pretreatment resulted in a 3-fold increase in locomotor activity following injection of d-amphetamine, 5 mg/kg. No sensitization or changes in catecholamine levels were observed in amphetamine-treated A/J mice. These results suggest that the sensitization produced by amphetamine pretreatment may be related to the depletion of brain norepinephrine.", "contents": "Changes in brain norepinephrine associated with sensitization to d-amphetamine. Pretreatment of B6AF1/J mice with d-amphetamine HCl 10 mg/kg, twice daily for 5 days, produced a 4-fold increase in the running response to a test dose of 5 mg/kg amphetamine. Amphetamine pretreatment decreased whole-brain norepinephrine levels to 50% of control values and whole-brain dopamine to 85%. The test dose of 5 mg/kg amphetamine lowered whole brain norepinephrine levels of control mice from 0.50 mug/g to 0.28 mug/g in 2 h. In amphetamine-pretreated mice, this injection caused an increase in whole-brain norepinephrine levels from 0.22 mug/g to 0.55 mug/g at 30 min, followed by a decrease to 0.22 mug/g at 60 min. No change in whole brain dopamine levels was observed in either group. Amphetamine sensitization and norepinephrine depletion were still evident 25 days after pretreatment. No cross sensitization to morphine or cocaine was observed. Reserpine pretreatment resulted in a 3-fold increase in locomotor activity following injection of d-amphetamine, 5 mg/kg. No sensitization or changes in catecholamine levels were observed in amphetamine-treated A/J mice. These results suggest that the sensitization produced by amphetamine pretreatment may be related to the depletion of brain norepinephrine."}
{"id": "PMID:9658", "title": "Effects of a novel anti-aggressive agent upon two types of brain stimulated emotional behavior.", "content": "The effects of anti-aggressive agent Sch 12679 were evaluated upon stable baselines of rage and predation elicited by electrical stimulation of the hypothalamus in cats. Sch 12679 depressed approach and terminal aspects of both forms of attack. This is consistent with previous reports, and suggests the drug is effective in reducing many forms of aggression including brain stimulated emotional behavior.", "contents": "Effects of a novel anti-aggressive agent upon two types of brain stimulated emotional behavior. The effects of anti-aggressive agent Sch 12679 were evaluated upon stable baselines of rage and predation elicited by electrical stimulation of the hypothalamus in cats. Sch 12679 depressed approach and terminal aspects of both forms of attack. This is consistent with previous reports, and suggests the drug is effective in reducing many forms of aggression including brain stimulated emotional behavior."}
{"id": "PMID:9659", "title": "Effects of combined treatment with nortriptiline and lorazepam on conflict behavior and motility of rats.", "content": "Lorazepam attenuated the suppressant effects of punishment on the response rate of rats in the multiple schedule of reinforcement devised by Geller and Seifter (1960). Nortriptiline alone was ineffective on punished responses. Both drugs, at certain dose levels, inhibited the nonpunished response. Combined treatment with the two drugs in a dose ratio of 1:20 attenuated the effects of punishment at all dose levels tested. The effects of the combination upon both punished and nonpunished responding was greater than might be accounted for by a simple additive effect of the individual treatments. Lorazepam and nortriptiline both induced a dose-related decrease in the locomotor activity of rats; when given together the 2 drugs antagonized each other. The results give an experimental support to the clinical observations about the usefulness of the benzodiazepine-antidepressant combination in certain depressive illnesses.", "contents": "Effects of combined treatment with nortriptiline and lorazepam on conflict behavior and motility of rats. Lorazepam attenuated the suppressant effects of punishment on the response rate of rats in the multiple schedule of reinforcement devised by Geller and Seifter (1960). Nortriptiline alone was ineffective on punished responses. Both drugs, at certain dose levels, inhibited the nonpunished response. Combined treatment with the two drugs in a dose ratio of 1:20 attenuated the effects of punishment at all dose levels tested. The effects of the combination upon both punished and nonpunished responding was greater than might be accounted for by a simple additive effect of the individual treatments. Lorazepam and nortriptiline both induced a dose-related decrease in the locomotor activity of rats; when given together the 2 drugs antagonized each other. The results give an experimental support to the clinical observations about the usefulness of the benzodiazepine-antidepressant combination in certain depressive illnesses."}
{"id": "PMID:9660", "title": "Mepiprazole, a new psychotropic drug: effects on uptake and retention of monoamines in rat brain synaptosomes.", "content": "The influence of mepiprazole (EMD 16,923), a new pyrazol-ylalkyl-piperazine derivative, on the uptake of 3H-norepinephrine (NE), 3H-dopamine (DA), and 3H-serotonin (5-HT) into rat brain synaptosomes from cerebral cortex, corpus striatum, and hypothalamus was investigated in comparison with several psychotropic drugs, including oxypertine, d-amphetamine, imipramine, desipramine, chlorimipramine, amitriptyline, and chlorpromazine in vitro. Mepiprazole was a relatively weak inhibitor of monoamine uptake and exhibited its strongest action on the hypothalamic 5-HT uptake, being almost equipotent with desipramine (IC50 = 0.9 MUM). Furthermore, the influence of the drugs on the retention of 3H-amines previously taken up by whole rat brain synaptosomes was studied. Unlike the tricyclic antidepressants, mepiprazole as well as oxypertine and d-amphetamine markedly increased the efflux of radioactivity during a 20-min incubation at 37 degrees C at low concentrations (10(-6) to 10(-5) M), whereas at 10(-4) M all drugs greatly enhanced the efflux. The ability of mepiprazole to increase 5-HT concentration at the receptor level by a combination of neuronal uptake inhibition and release is discussed in relationship to the central actions of the drug.", "contents": "Mepiprazole, a new psychotropic drug: effects on uptake and retention of monoamines in rat brain synaptosomes. The influence of mepiprazole (EMD 16,923), a new pyrazol-ylalkyl-piperazine derivative, on the uptake of 3H-norepinephrine (NE), 3H-dopamine (DA), and 3H-serotonin (5-HT) into rat brain synaptosomes from cerebral cortex, corpus striatum, and hypothalamus was investigated in comparison with several psychotropic drugs, including oxypertine, d-amphetamine, imipramine, desipramine, chlorimipramine, amitriptyline, and chlorpromazine in vitro. Mepiprazole was a relatively weak inhibitor of monoamine uptake and exhibited its strongest action on the hypothalamic 5-HT uptake, being almost equipotent with desipramine (IC50 = 0.9 MUM). Furthermore, the influence of the drugs on the retention of 3H-amines previously taken up by whole rat brain synaptosomes was studied. Unlike the tricyclic antidepressants, mepiprazole as well as oxypertine and d-amphetamine markedly increased the efflux of radioactivity during a 20-min incubation at 37 degrees C at low concentrations (10(-6) to 10(-5) M), whereas at 10(-4) M all drugs greatly enhanced the efflux. The ability of mepiprazole to increase 5-HT concentration at the receptor level by a combination of neuronal uptake inhibition and release is discussed in relationship to the central actions of the drug."}
{"id": "PMID:9675", "title": "Time course of free and N4-acetylated sulfapyridine concentrations in the plasma and saliva of man after sulfasalazine (salicylazosulfapyridine) administration: preliminary findings.", "content": "The time course of free and N4-acetylated sulfapyridine (SP) concentrations in the saliva and whole plasma was determined in a healthy male volunteer after a single 2.0 g oral dose of salicylazosulfapyridine (SASP) as four-500 mg commercial, uncoated tablets. The mean (+/- S.D.) plasma: saliva concentration ratios for free and acetylated SP was 2.04 (+/- 0.24) and 3.12 (+/-0.43), respectively, and were independent of plasma concentration and saliva pH. The elimination half-lives of SP and N4-acetyl SP could be determined from either salivary or plasma concentration-time data. These preliminary results suggest that measurement of saliva concentrations of free and acetylated SP may be a convenient, noninvasive method for monitoring indirectly the plasma concentrations of SP and acetyl SP in patients treated with SASP and for determining acetylator phenotype.", "contents": "Time course of free and N4-acetylated sulfapyridine concentrations in the plasma and saliva of man after sulfasalazine (salicylazosulfapyridine) administration: preliminary findings. The time course of free and N4-acetylated sulfapyridine (SP) concentrations in the saliva and whole plasma was determined in a healthy male volunteer after a single 2.0 g oral dose of salicylazosulfapyridine (SASP) as four-500 mg commercial, uncoated tablets. The mean (+/- S.D.) plasma: saliva concentration ratios for free and acetylated SP was 2.04 (+/- 0.24) and 3.12 (+/-0.43), respectively, and were independent of plasma concentration and saliva pH. The elimination half-lives of SP and N4-acetyl SP could be determined from either salivary or plasma concentration-time data. These preliminary results suggest that measurement of saliva concentrations of free and acetylated SP may be a convenient, noninvasive method for monitoring indirectly the plasma concentrations of SP and acetyl SP in patients treated with SASP and for determining acetylator phenotype."}
{"id": "PMID:9676", "title": "Model to study long-term effects of propoxyphene napsylate (darvon-N) on narcotic-dependent mice.", "content": "Five different strains of mice were investigated for their suitability to serve as models for the study of long-term effects of propoxyphene napsylate (PN) on narcotic-dependent mice. The NIH/Swiss outbred strain proved to be most suitable because of its high liability to manifest physical dependence on morphine. Following removal of subcutaneously-implanted morphine pellets from the mice, the incidence of spontaneous withdrawal jumping was used as a quantifiable criterion of physical dependence. An orally administered suspension of PN suppressed the withdrawal jumping in a dose-dependent manner. However, chronic (daily) administration of PN at doses high enough to prevent withdrawal jumping was characterized by a high degree of toxicity.", "contents": "Model to study long-term effects of propoxyphene napsylate (darvon-N) on narcotic-dependent mice. Five different strains of mice were investigated for their suitability to serve as models for the study of long-term effects of propoxyphene napsylate (PN) on narcotic-dependent mice. The NIH/Swiss outbred strain proved to be most suitable because of its high liability to manifest physical dependence on morphine. Following removal of subcutaneously-implanted morphine pellets from the mice, the incidence of spontaneous withdrawal jumping was used as a quantifiable criterion of physical dependence. An orally administered suspension of PN suppressed the withdrawal jumping in a dose-dependent manner. However, chronic (daily) administration of PN at doses high enough to prevent withdrawal jumping was characterized by a high degree of toxicity."}
{"id": "PMID:9677", "title": "In vitro studies on the antimicrobial effects of colostrum and milk from vaccinated and unvaccinated pigs on Escherichia coli.", "content": "Unsupplemented porcine colostrum and milk exhibited a powerful bactericidal effect for porcine strains of E coli incubated in vitro at 37 degrees C. This activity was independent of complement but was susceptible to acid pH, to the presence of soluble iron and to the selective immunoprecipitation of IgG, IgA and IgM. Manifestation of bactericidal activity required bacteria in an active state of metabolism and the length of incubation was an important factor in demonstrating the quality of the anticoli activity, ie, proliferation-inhibitory, bacteriostatic or bactericidal. Whey obtained by acid precipitation or by the application of rennin was devoid of bactericidal activity but was capable of slowing down proliferation of E coli. There was no correlation between lysozyme and anticoli activity although the complete removal of lysozyme by adsorption on to bentonite reduced bactericidal titres. With very few exceptions the highest bactericidal titres were recorded for colostrum, but even 28 days post partum about one half of 22 undiluted milk samples exhibired bactericidal activity.", "contents": "In vitro studies on the antimicrobial effects of colostrum and milk from vaccinated and unvaccinated pigs on Escherichia coli. Unsupplemented porcine colostrum and milk exhibited a powerful bactericidal effect for porcine strains of E coli incubated in vitro at 37 degrees C. This activity was independent of complement but was susceptible to acid pH, to the presence of soluble iron and to the selective immunoprecipitation of IgG, IgA and IgM. Manifestation of bactericidal activity required bacteria in an active state of metabolism and the length of incubation was an important factor in demonstrating the quality of the anticoli activity, ie, proliferation-inhibitory, bacteriostatic or bactericidal. Whey obtained by acid precipitation or by the application of rennin was devoid of bactericidal activity but was capable of slowing down proliferation of E coli. There was no correlation between lysozyme and anticoli activity although the complete removal of lysozyme by adsorption on to bentonite reduced bactericidal titres. With very few exceptions the highest bactericidal titres were recorded for colostrum, but even 28 days post partum about one half of 22 undiluted milk samples exhibired bactericidal activity."}
{"id": "PMID:9678", "title": "Aquatic life at high altitude: respiratory adaptations in the Lake Titicaca frog, Telmatobius culeus.", "content": "Telmatobius culeus has a combination of behavioral, morphological and physiological adaptations which allows an aquatic life in cool (10 degrees C) O2-saturated (at 100 mm Hg) waters at high altitude (3812 m). The skin surgace area is increased by pronounced folds and the cutaneous capillaries penetrate to the outer layers of the skin. The erythrocyte volume (394 mu3) is the smallest reported for amphibians. The P50 (15.6 at ph 7.65 and 10 degrees C) is the lowest, and the erythrocyte count (729 - 103/mm3) the highest for an anuran. The O2 capacity (11.7 vol%), hemoglobin (8.1 g/100 ml), hemoglobin concentration (0.281 pg/mu3) and hematocrit (27.9%) measured at 18 degrees C and 3800 m are all elevated in comparison with most amphibians. The O2 dissociation curve is sigmoid (n = 2), the Bohr factor is small (deltalog P50/deltapH = -0.30) and the buffering capacity (-8.9 m M HCO3 - 1-1) is typical for an aquatic amphibian. The metabolic rate (14.1 mul -g-1-h-u) is the lowest reported for a frog and among amphibians only the giant salamanders (Amphiuma, Necturus and Siren) have lower values. If prevent from surfacing in hypoxic waters, the frogs ventilate the skin by \"bobbing\" behavior; if allowed to surface, they will ventilate the small lungs and the metabolic rate increases to 23 mul-g-1-h-1.", "contents": "Aquatic life at high altitude: respiratory adaptations in the Lake Titicaca frog, Telmatobius culeus. Telmatobius culeus has a combination of behavioral, morphological and physiological adaptations which allows an aquatic life in cool (10 degrees C) O2-saturated (at 100 mm Hg) waters at high altitude (3812 m). The skin surgace area is increased by pronounced folds and the cutaneous capillaries penetrate to the outer layers of the skin. The erythrocyte volume (394 mu3) is the smallest reported for amphibians. The P50 (15.6 at ph 7.65 and 10 degrees C) is the lowest, and the erythrocyte count (729 - 103/mm3) the highest for an anuran. The O2 capacity (11.7 vol%), hemoglobin (8.1 g/100 ml), hemoglobin concentration (0.281 pg/mu3) and hematocrit (27.9%) measured at 18 degrees C and 3800 m are all elevated in comparison with most amphibians. The O2 dissociation curve is sigmoid (n = 2), the Bohr factor is small (deltalog P50/deltapH = -0.30) and the buffering capacity (-8.9 m M HCO3 - 1-1) is typical for an aquatic amphibian. The metabolic rate (14.1 mul -g-1-h-u) is the lowest reported for a frog and among amphibians only the giant salamanders (Amphiuma, Necturus and Siren) have lower values. If prevent from surfacing in hypoxic waters, the frogs ventilate the skin by \"bobbing\" behavior; if allowed to surface, they will ventilate the small lungs and the metabolic rate increases to 23 mul-g-1-h-1."}
{"id": "PMID:9679", "title": "The oxygen affinity of chicken haemoglobin in whole blood and erythrocyte suspensions.", "content": "The oxygen equilibrium of whole chicken blood has a P50 of 52.3 mm Hg and a Hill coefficient of 2.6 at pH 7.4 and 37 degrees C when determined with new microtechniques which are not vitiated by cellular respiration. The apparent failure of the haemoglobin to reach full saturation at arterial PO2 IS DISCUSSED IN RELATION TO THE HAEMoglobin-oxygen equilibrium concept. The low affinity observed is due to intraerythrocytic inositol pentaphosphate (IPP), and the affinity of a haemolysate \"stripped\" of IPP is greatly increased (deltalog P50 =1.25). Unlike the mamalian analogue 2, 3-diphosphoglycerate, IPP concentration of whole blood does not decrease after incubation for 10 hr at 37 degreesC.", "contents": "The oxygen affinity of chicken haemoglobin in whole blood and erythrocyte suspensions. The oxygen equilibrium of whole chicken blood has a P50 of 52.3 mm Hg and a Hill coefficient of 2.6 at pH 7.4 and 37 degrees C when determined with new microtechniques which are not vitiated by cellular respiration. The apparent failure of the haemoglobin to reach full saturation at arterial PO2 IS DISCUSSED IN RELATION TO THE HAEMoglobin-oxygen equilibrium concept. The low affinity observed is due to intraerythrocytic inositol pentaphosphate (IPP), and the affinity of a haemolysate \"stripped\" of IPP is greatly increased (deltalog P50 =1.25). Unlike the mamalian analogue 2, 3-diphosphoglycerate, IPP concentration of whole blood does not decrease after incubation for 10 hr at 37 degreesC."}
{"id": "PMID:9682", "title": "[The role of arthropods as vector agents in viral hepatitis].", "content": "The increased incidence during the last years of viral hepatitis demands a new approach to the various eventual possibilities of contamination. The author discusses the transmission of serum hepatitis by mosquitoes, especially in warm climates, and the recent results obtained in investigations on the mechanical or biological transmission by haematophage arthropods.", "contents": "[The role of arthropods as vector agents in viral hepatitis]. The increased incidence during the last years of viral hepatitis demands a new approach to the various eventual possibilities of contamination. The author discusses the transmission of serum hepatitis by mosquitoes, especially in warm climates, and the recent results obtained in investigations on the mechanical or biological transmission by haematophage arthropods."}
{"id": "PMID:9689", "title": "The value of epicillin and ampicillin in the treatment of meningococcal and pneumococcal meningitis.", "content": "96 patients with meningitis due to Neisseria meningitidis and Diplococcus pneumoniae were treated with epicillin or ampicillin according to a predesigned randomization chart. Results indicate that epicillin and ampicillin are effective single drugs in the treatment of meningococcal and pneumococcal meningitis. No adverse reactions were noted with either drug and they were comparable in their efficacy.", "contents": "The value of epicillin and ampicillin in the treatment of meningococcal and pneumococcal meningitis. 96 patients with meningitis due to Neisseria meningitidis and Diplococcus pneumoniae were treated with epicillin or ampicillin according to a predesigned randomization chart. Results indicate that epicillin and ampicillin are effective single drugs in the treatment of meningococcal and pneumococcal meningitis. No adverse reactions were noted with either drug and they were comparable in their efficacy."}
{"id": "PMID:9688", "title": "Disorders induced by pheochromocytoma in the cardiovascular system. A therapeutic approach.", "content": "The diagnosis of pheochromocytoms is still made only post mortem in a high percentage of the cases. It is important to know both the diversity of clinical forms (of the 16 cases investigated 13 (80%) presented permanent AH, of which 12 cases with paroxysmal attacks, followed by collapse only in one case, and 3 (20%) with paroxysmal AH on a normotensive background) and the severity of cardiovascular accidents, which increases twofold during crises (arrhythmias, left ventricular failure, coronary insufficiency, cerebrovascular strokes, secondary adrenalinic shocks). These complications are preceded by the \"alarm syndrome\". The preoperatory treatment is associated: blocking of adrenergic alpha-receptors and beta-receptors; correction of hypovolemia, also applied during the surgical phase I (until the venous ligature is made and the tumor excised) under continuous monitoring (ECG, ABP and central venous pressure). In phase II vasoplegin should be promptly corrected by nor. E+E, and corticoids.", "contents": "Disorders induced by pheochromocytoma in the cardiovascular system. A therapeutic approach. The diagnosis of pheochromocytoms is still made only post mortem in a high percentage of the cases. It is important to know both the diversity of clinical forms (of the 16 cases investigated 13 (80%) presented permanent AH, of which 12 cases with paroxysmal attacks, followed by collapse only in one case, and 3 (20%) with paroxysmal AH on a normotensive background) and the severity of cardiovascular accidents, which increases twofold during crises (arrhythmias, left ventricular failure, coronary insufficiency, cerebrovascular strokes, secondary adrenalinic shocks). These complications are preceded by the \"alarm syndrome\". The preoperatory treatment is associated: blocking of adrenergic alpha-receptors and beta-receptors; correction of hypovolemia, also applied during the surgical phase I (until the venous ligature is made and the tumor excised) under continuous monitoring (ECG, ABP and central venous pressure). In phase II vasoplegin should be promptly corrected by nor. E+E, and corticoids."}
{"id": "PMID:9692", "title": "Cholinergic stimulation of the rat hypothalamus: effects of liver glycogen synthesis.", "content": "Cholinergic stimulation of the lateral hypothalamic neurons with intrahypothalamic microinjections of acetylcholine or carbachol caused a marked increase in the content of the active form of glycogen (starch) synthase in the liver. Total activity of the enzyme (active plus inactive forms) was not increased significantly. The lowest effective dose of acetylcholine was 5 X 10(-10) mole, and the optimum dose was 5 X 10(-9) mole. Similar applications of other neurotransmitters, such as norepinephrine, dopamine, serotonin, and gamma-aminobutyric acid, did not affect the enzyme's activity.", "contents": "Cholinergic stimulation of the rat hypothalamus: effects of liver glycogen synthesis. Cholinergic stimulation of the lateral hypothalamic neurons with intrahypothalamic microinjections of acetylcholine or carbachol caused a marked increase in the content of the active form of glycogen (starch) synthase in the liver. Total activity of the enzyme (active plus inactive forms) was not increased significantly. The lowest effective dose of acetylcholine was 5 X 10(-10) mole, and the optimum dose was 5 X 10(-9) mole. Similar applications of other neurotransmitters, such as norepinephrine, dopamine, serotonin, and gamma-aminobutyric acid, did not affect the enzyme's activity."}
{"id": "PMID:9696", "title": "Beta-blockers and the central nervous system.", "content": "Some of the interesting points which emerged from an international symposium on beta-blockers and the central nervous system, held in St Moritz in January 1976, are presented. Fifty-eight participants from 12 countries attended the symposium.", "contents": "Beta-blockers and the central nervous system. Some of the interesting points which emerged from an international symposium on beta-blockers and the central nervous system, held in St Moritz in January 1976, are presented. Fifty-eight participants from 12 countries attended the symposium."}
{"id": "PMID:9697", "title": "Somatostatin, 1976.", "content": "Somatostatin, a growth hormone release-inhibiting factor, isolated originally from the hypothalamus, has been shown to have widespread effects on brain and endocrine and exocrine pancreatic and gut function. Furthermore, it has a widespread distribution in the CNS, gut and C cells of the thyroid -- cells which probably migrated originally from the neural crest during development. While the pharmacological effects of somatostatin are diffuse, its physiological role is at present unknown, but in view of its concentration in synaptosomal fractions of neural tissue, it may have a neurotransmitter or a synaptic modulator function.", "contents": "Somatostatin, 1976. Somatostatin, a growth hormone release-inhibiting factor, isolated originally from the hypothalamus, has been shown to have widespread effects on brain and endocrine and exocrine pancreatic and gut function. Furthermore, it has a widespread distribution in the CNS, gut and C cells of the thyroid -- cells which probably migrated originally from the neural crest during development. While the pharmacological effects of somatostatin are diffuse, its physiological role is at present unknown, but in view of its concentration in synaptosomal fractions of neural tissue, it may have a neurotransmitter or a synaptic modulator function."}
{"id": "PMID:9699", "title": "Severe ischemia of the hand following radial artery catheterization.", "content": "Percutaneous radial artery catheterization for blood gas monitoring and continuous arterial pressure recording has become a common place procedure in the management of critically ill patients. Five patients with severe ischemia after cannulation have been encountered in the past 20 months, four of whom lost segments of one or more digits. Review of the events preceding and during radial artery cannulation allowed elucidation of the following principles: radial artery catheterization should be preceded always by a negative Allen test; the catheter should be removed after 12 to 18 hours, especially if the patient is critically ill, is hypercoagulable, or has impaired tissue perfusion; the superficial temporal artery is safer to use and permits long-term cannulation (5 to 7 days) without ill effect; and agressive approach to assessing flow and arterial reconstruction is essential if severe ischemic symptoms occur during or after radial artery catheterization. Ancillary measures, including cervicodorsal sympathetic block, intravenous low molecular weight dextran and heparin, and intra-arterial reserpine and fibrinolysin, may improve palmar circulation but should not be substituted for both noninvasive and angiographic study of arterial flow, followed by surgical restoration of flow, when indicated.", "contents": "Severe ischemia of the hand following radial artery catheterization. Percutaneous radial artery catheterization for blood gas monitoring and continuous arterial pressure recording has become a common place procedure in the management of critically ill patients. Five patients with severe ischemia after cannulation have been encountered in the past 20 months, four of whom lost segments of one or more digits. Review of the events preceding and during radial artery cannulation allowed elucidation of the following principles: radial artery catheterization should be preceded always by a negative Allen test; the catheter should be removed after 12 to 18 hours, especially if the patient is critically ill, is hypercoagulable, or has impaired tissue perfusion; the superficial temporal artery is safer to use and permits long-term cannulation (5 to 7 days) without ill effect; and agressive approach to assessing flow and arterial reconstruction is essential if severe ischemic symptoms occur during or after radial artery catheterization. Ancillary measures, including cervicodorsal sympathetic block, intravenous low molecular weight dextran and heparin, and intra-arterial reserpine and fibrinolysin, may improve palmar circulation but should not be substituted for both noninvasive and angiographic study of arterial flow, followed by surgical restoration of flow, when indicated."}
{"id": "PMID:9702", "title": "Bacterial precipitins and their immunoglobulin class in atopic asthma, non-atopic asthma, and chronic bronchitis.", "content": "In a study of groups of patients with atopic (extrinsic) asthma, non-atopic (intrinsic) asthma, and chronic bronchitis, no difference could be detected in the numbers having precipitating antibodies against species specific antigens from Staphylococcus aureus or Streptococcus pneumoniae compared to suitably matched control subjects. Precipitating antibodies against species specific antigens from Haemophilus influenzae, demonstrated in this investigation by double diffusion in agar gel, were found much more frequently in patients with chronic mucopurulent or obstructive bronchitis (50%) than in either asthmatic subjects (6%) or normal controls (6%) (P = less than 0.0005). While the precipitating antibody demonstrated in these patients against the extracts of Str. pneumoniae and Staph. aureus was in the IgG class alone, IgM and IgA antibody were detected against the species specific but not the non-species specific antigens of H. influenzae. These results underline the importance of H. influenzae as an infecting agent in chronic bronchitis and suggest that the finding of precipitins against the species specific H1 and H2 antigens of this bacterium denotes infection either concurrently or in the recent past. There is no evidence to suggest from this study that infection with Staph. aureus, Str. pneumoniae or H. influenzae is any more common in asthmatics as a group compared to controls or between patients with the non-atopic (intrinsic) and atopic (extrinsic) form of the disease.", "contents": "Bacterial precipitins and their immunoglobulin class in atopic asthma, non-atopic asthma, and chronic bronchitis. In a study of groups of patients with atopic (extrinsic) asthma, non-atopic (intrinsic) asthma, and chronic bronchitis, no difference could be detected in the numbers having precipitating antibodies against species specific antigens from Staphylococcus aureus or Streptococcus pneumoniae compared to suitably matched control subjects. Precipitating antibodies against species specific antigens from Haemophilus influenzae, demonstrated in this investigation by double diffusion in agar gel, were found much more frequently in patients with chronic mucopurulent or obstructive bronchitis (50%) than in either asthmatic subjects (6%) or normal controls (6%) (P = less than 0.0005). While the precipitating antibody demonstrated in these patients against the extracts of Str. pneumoniae and Staph. aureus was in the IgG class alone, IgM and IgA antibody were detected against the species specific but not the non-species specific antigens of H. influenzae. These results underline the importance of H. influenzae as an infecting agent in chronic bronchitis and suggest that the finding of precipitins against the species specific H1 and H2 antigens of this bacterium denotes infection either concurrently or in the recent past. There is no evidence to suggest from this study that infection with Staph. aureus, Str. pneumoniae or H. influenzae is any more common in asthmatics as a group compared to controls or between patients with the non-atopic (intrinsic) and atopic (extrinsic) form of the disease."}
{"id": "PMID:9703", "title": "The effect of beta adrenergic blockade upon exercise-induced changes in blood coagulation and fibrinolysis.", "content": "Exercise stress is known to stimulate blood coagulation and fibrinolysis possibly as a result of sympatho-adrenal stimulation of the beta adrenergic receptor. In order to test this hypothesis five men exercised on four separate occasions with and without prior beta adrenergic blockade with oxprenolol, propranolol and pindolol. The increase in plasma adrenaline and noradrenaline concentration was much greater during exercise under beta blockade but activation of fibrinolysis was enhanced as well. Factor VIII levels did not change significantly during any of the experiments. These results suggest that the activation of fibrinolysis by exercise is not mediated by the beta adrenergic receptor. The influence of beta adrenergic blockade on the change in factor VIII with exercise was inconclusive.", "contents": "The effect of beta adrenergic blockade upon exercise-induced changes in blood coagulation and fibrinolysis. Exercise stress is known to stimulate blood coagulation and fibrinolysis possibly as a result of sympatho-adrenal stimulation of the beta adrenergic receptor. In order to test this hypothesis five men exercised on four separate occasions with and without prior beta adrenergic blockade with oxprenolol, propranolol and pindolol. The increase in plasma adrenaline and noradrenaline concentration was much greater during exercise under beta blockade but activation of fibrinolysis was enhanced as well. Factor VIII levels did not change significantly during any of the experiments. These results suggest that the activation of fibrinolysis by exercise is not mediated by the beta adrenergic receptor. The influence of beta adrenergic blockade on the change in factor VIII with exercise was inconclusive."}
{"id": "PMID:9704", "title": "Studies on the action mechanism of the antihemostatic effect of lodopeptides.", "content": "A synthetic iodopeptide having a glutamic acid-diiodotyrosine molar ratio of 1:1 has been shown to be an effective anticoagulant both in vivo and in vitro. Contrasted with heparin the following general conclusions may be made regarding its action. The iodopeptide does not act through the inactivation of thrombin in plasma. Iodopeptide does interact with fibrinogen to form a complex which, in vitro, is not soluble in buffered saline at physiological pH. At pH 8, iodopeptide interacts with fibrinogen to form a soluble complex in the presence of 0.9% NaCl that is not coaguable either by thrombin or Crotalus venom enzymes. All the available evidence indicates that the fibrinogen to fibrin conversion is not inhibited under these conditions, but that fibrin, once formed, is not able to polymerize due to interference by iodopeptide. Similar results were obtained with heparin in vitro with thrombin-fibrinogen mixtures in the absence of NaCl. Studies with Russell's viper venom in native PRP strongly suggest that the iodopeptide also interferes with processes in the early coagulation pathway associated with prothrombin activation.", "contents": "Studies on the action mechanism of the antihemostatic effect of lodopeptides. A synthetic iodopeptide having a glutamic acid-diiodotyrosine molar ratio of 1:1 has been shown to be an effective anticoagulant both in vivo and in vitro. Contrasted with heparin the following general conclusions may be made regarding its action. The iodopeptide does not act through the inactivation of thrombin in plasma. Iodopeptide does interact with fibrinogen to form a complex which, in vitro, is not soluble in buffered saline at physiological pH. At pH 8, iodopeptide interacts with fibrinogen to form a soluble complex in the presence of 0.9% NaCl that is not coaguable either by thrombin or Crotalus venom enzymes. All the available evidence indicates that the fibrinogen to fibrin conversion is not inhibited under these conditions, but that fibrin, once formed, is not able to polymerize due to interference by iodopeptide. Similar results were obtained with heparin in vitro with thrombin-fibrinogen mixtures in the absence of NaCl. Studies with Russell's viper venom in native PRP strongly suggest that the iodopeptide also interferes with processes in the early coagulation pathway associated with prothrombin activation."}
{"id": "PMID:9712", "title": "Canine allogeneic bone marrow transplantation. Technique and variables influencing engraftment.", "content": "We have studied the toxicity and immune suppression of supralethal total body irradiation (800-2000 rads, 60Co) at three dose intensities (10 rads/min, 49 rads/min, and 100 rads/min). In 79 intensively supported radiation control animals, the LD50(5) (tn 5 days) for these dose intensities is estimated to be 1556, 941, and 921 rads, respectively. A biomodal pattern of early (median 4 days) and late (median 9 days) deaths was observed corresponding to histopathological evidence of the intestinal and hematopoietic radiation syndromes. Random donor bone marrow transplants were performed in 83 animals to test immune suppression afforded by 800 rads and 1000 rads at dose intensities of either 10 rads/min or 49 rads/min. Bone marrow cell dose was varied to analyze its effect on engraftment. A greater degree of immunosuppression with less toxicity was achieved at the lower dose intensity. A minimum dose of 3-5 X 10(8) nucleated allogeneic bone marrow cells/kg (readily obtainable from living donors) resulted in a high percentage of engraftment with lethal graft-versus-host disease following conditioning with 1,000 rads midplane at 10 rads/min, the optimum regimen employed.", "contents": "Canine allogeneic bone marrow transplantation. Technique and variables influencing engraftment. We have studied the toxicity and immune suppression of supralethal total body irradiation (800-2000 rads, 60Co) at three dose intensities (10 rads/min, 49 rads/min, and 100 rads/min). In 79 intensively supported radiation control animals, the LD50(5) (tn 5 days) for these dose intensities is estimated to be 1556, 941, and 921 rads, respectively. A biomodal pattern of early (median 4 days) and late (median 9 days) deaths was observed corresponding to histopathological evidence of the intestinal and hematopoietic radiation syndromes. Random donor bone marrow transplants were performed in 83 animals to test immune suppression afforded by 800 rads and 1000 rads at dose intensities of either 10 rads/min or 49 rads/min. Bone marrow cell dose was varied to analyze its effect on engraftment. A greater degree of immunosuppression with less toxicity was achieved at the lower dose intensity. A minimum dose of 3-5 X 10(8) nucleated allogeneic bone marrow cells/kg (readily obtainable from living donors) resulted in a high percentage of engraftment with lethal graft-versus-host disease following conditioning with 1,000 rads midplane at 10 rads/min, the optimum regimen employed."}
{"id": "PMID:9713", "title": "Graft-versus-host reactivity and renal allograft survival in rats given allogeneic spleen cells or spleen allografts.", "content": "Selective recruitment of antigen-sensitive cells (ASC) into the spleen as a method of inducing specific suppression was attempted by intravenous injection of either DA or Lewis spleen cells 24 hr before a (DA X Lewis)F1 renal allograft into a Lewis or DA recipient, either with or without a splenectomy. This led to suppression of rejection in the DA recipient and delayed rejection in the Lewis recipient. Splenectomy produced a minimal augmentation effect. Assay of graft-versus-host (GVH) reactions in (DA X Lewis)F1 rats by a popliteal node assay showed that injection of allogeneic DA or Lewis spleen cells 48 hr before the assay significantly reduced the reaction produced by node lymphocytes but not spleen lymphocytes, suggesting a loss of ASC from the lymph nodes. Lewis spleen allografts did not produce such a significant reduction in the GVH reactivity of DA node lymphocytes as intravenous Lewis cells, whereas DA spleen allografts led to an increased GVH reactivity of Lewis node lymphocytes. From these studies, it is not possible to attribute the suppression produced by the intravenous injection of allogeneic cells to selective recruitment of antigen-sensitive cells to the spleen.", "contents": "Graft-versus-host reactivity and renal allograft survival in rats given allogeneic spleen cells or spleen allografts. Selective recruitment of antigen-sensitive cells (ASC) into the spleen as a method of inducing specific suppression was attempted by intravenous injection of either DA or Lewis spleen cells 24 hr before a (DA X Lewis)F1 renal allograft into a Lewis or DA recipient, either with or without a splenectomy. This led to suppression of rejection in the DA recipient and delayed rejection in the Lewis recipient. Splenectomy produced a minimal augmentation effect. Assay of graft-versus-host (GVH) reactions in (DA X Lewis)F1 rats by a popliteal node assay showed that injection of allogeneic DA or Lewis spleen cells 48 hr before the assay significantly reduced the reaction produced by node lymphocytes but not spleen lymphocytes, suggesting a loss of ASC from the lymph nodes. Lewis spleen allografts did not produce such a significant reduction in the GVH reactivity of DA node lymphocytes as intravenous Lewis cells, whereas DA spleen allografts led to an increased GVH reactivity of Lewis node lymphocytes. From these studies, it is not possible to attribute the suppression produced by the intravenous injection of allogeneic cells to selective recruitment of antigen-sensitive cells to the spleen."}
{"id": "PMID:9714", "title": "Disseminated systemic expression of the \"local\" popliteal lymph node assay in rats.", "content": "In contrast to the traditional belief that the popliteal lymph node (PLN) assay of graft-versus-host (GVH) reactivity is a local phenomenon, this study describes significant systemic components of both donor and host lymphoid cell activity. Not only are host radiosensitive lymphocytes of systemic origin necessary for the manifestation of normal PLN hypertrophy, but as few as 2.5 X 10(6) parental lymph node cells (LNCs) injected into the hind footpad of adult F1 hybrid rats disseminate widely, provoking significant systemic GVH reactions, as measured by splenomegaly, and distant lymphadenopathy. Futhermore, locally injected donor LNCs ultimately engender three forms of attenuated GVH reactivity: (1) the dissipation of potentially unlimited GVH reactivity, (2) refractoriness of the host to subsequent rechallenge by GVH-inducing cells, and (3) progressive loss of GVH reactivity in donor LNCs when serially transferred to secondary F1 recipients. Whether this modulation of the cell-mediated immune response is the expression of an anti-recognition structure response by the host or the activation of some other immunoregulatory protein, it is absent or reduced in splenectomized recipients. The data suggest that the spleen provides an immunoregulatory microenvironment in which cell-mediated immune responses, such as the GVH reaction, are modulated.", "contents": "Disseminated systemic expression of the \"local\" popliteal lymph node assay in rats. In contrast to the traditional belief that the popliteal lymph node (PLN) assay of graft-versus-host (GVH) reactivity is a local phenomenon, this study describes significant systemic components of both donor and host lymphoid cell activity. Not only are host radiosensitive lymphocytes of systemic origin necessary for the manifestation of normal PLN hypertrophy, but as few as 2.5 X 10(6) parental lymph node cells (LNCs) injected into the hind footpad of adult F1 hybrid rats disseminate widely, provoking significant systemic GVH reactions, as measured by splenomegaly, and distant lymphadenopathy. Futhermore, locally injected donor LNCs ultimately engender three forms of attenuated GVH reactivity: (1) the dissipation of potentially unlimited GVH reactivity, (2) refractoriness of the host to subsequent rechallenge by GVH-inducing cells, and (3) progressive loss of GVH reactivity in donor LNCs when serially transferred to secondary F1 recipients. Whether this modulation of the cell-mediated immune response is the expression of an anti-recognition structure response by the host or the activation of some other immunoregulatory protein, it is absent or reduced in splenectomized recipients. The data suggest that the spleen provides an immunoregulatory microenvironment in which cell-mediated immune responses, such as the GVH reaction, are modulated."}
{"id": "PMID:9715", "title": "Infection rate of arboviruses in Dutch recruits returning from Surinam.", "content": "Paired serum samples from approximately 650 Dutch recruits residing temporarily in Surinam, the first sample being collected on arrival, the second when leaving the country, were examined for haemagglutination-inhibiting antibodies to two types of arbovirus (Mucambo and Restan) isolated from local mosquitoes, and to two types of arbovirus (Oriboca and Caraparu) isolated from human blood. In a group of inidviduals in whom mild febrile illness had been reported, antibodies had developed in 3.9 to 6.7%, and in a group without reported history of febrile illness in 3.0 to 47% for each of the viruses.", "contents": "Infection rate of arboviruses in Dutch recruits returning from Surinam. Paired serum samples from approximately 650 Dutch recruits residing temporarily in Surinam, the first sample being collected on arrival, the second when leaving the country, were examined for haemagglutination-inhibiting antibodies to two types of arbovirus (Mucambo and Restan) isolated from local mosquitoes, and to two types of arbovirus (Oriboca and Caraparu) isolated from human blood. In a group of inidviduals in whom mild febrile illness had been reported, antibodies had developed in 3.9 to 6.7%, and in a group without reported history of febrile illness in 3.0 to 47% for each of the viruses."}
{"id": "PMID:9723", "title": "Sipple's syndrome. A urologist's viewpoint.", "content": "A case of Sipple's syndrome, a triad of medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid hyperplasia is presented. The cause, laboratory diagnosis, and operative management of the syndrome are discussed. The need for thorough endocrine screening of patients with pheochromocytoma and family screening of patients with the full syndrome is stressed.", "contents": "Sipple's syndrome. A urologist's viewpoint. A case of Sipple's syndrome, a triad of medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid hyperplasia is presented. The cause, laboratory diagnosis, and operative management of the syndrome are discussed. The need for thorough endocrine screening of patients with pheochromocytoma and family screening of patients with the full syndrome is stressed."}
{"id": "PMID:9724", "title": "Disorders of micturition: neuropharmacologic basis and results of drug therapy.", "content": "The clinical use of various pharmacologic agents in problems of micturition is based on the new concepts of intrinsic urethrovesical innervation, presence and regional predominance of autonomic neuroreceptors, and experimental evidence of the effects of various drugs on the bladder and the urethra. A new concept, relating to the processes that control bladder filling and emptying, is coming into being and replacing the traditional concept based on anatomic grounds alone. On the basis of the published data, and from personal experience both experimental and clinical, pharmacologic agents singly or in combination can be effectively and safely used in various problems of micturition such as incontinence (enuresis, stress incontinence in women, postprostatectomy, urgency incontinence), and functional outflow obstruction caused by neurologic or non-neurologic disease processes.", "contents": "Disorders of micturition: neuropharmacologic basis and results of drug therapy. The clinical use of various pharmacologic agents in problems of micturition is based on the new concepts of intrinsic urethrovesical innervation, presence and regional predominance of autonomic neuroreceptors, and experimental evidence of the effects of various drugs on the bladder and the urethra. A new concept, relating to the processes that control bladder filling and emptying, is coming into being and replacing the traditional concept based on anatomic grounds alone. On the basis of the published data, and from personal experience both experimental and clinical, pharmacologic agents singly or in combination can be effectively and safely used in various problems of micturition such as incontinence (enuresis, stress incontinence in women, postprostatectomy, urgency incontinence), and functional outflow obstruction caused by neurologic or non-neurologic disease processes."}
{"id": "PMID:9725", "title": "Host factors in urinary infections.", "content": "To prevent the urologist from becoming simply a urinary tract mechanic we must develop more specific tests, perfect present tests and use these tests to elicit faulty mechanisms of host resistance of patients with urinary tract infections. We must then provide, from our research information, therapeutic measures to protect the faulty host from the inconvenience of recurrent significant bacteriuria and its sequelae.", "contents": "Host factors in urinary infections. To prevent the urologist from becoming simply a urinary tract mechanic we must develop more specific tests, perfect present tests and use these tests to elicit faulty mechanisms of host resistance of patients with urinary tract infections. We must then provide, from our research information, therapeutic measures to protect the faulty host from the inconvenience of recurrent significant bacteriuria and its sequelae."}
{"id": "PMID:9728", "title": "Physical and chemical changes of ACD-preserved blood: a comparison of blood in glass bottles and plastic bags.", "content": "ACD blood was preserved in glass bottles with or without aeration and in plastic bags in air or nitrogen gas at 4.5 degrees C. The blood was examined for physical and chemical changes of erythrocyte membrane resistance, hemoglobin in the plasma, the viscosity of the blood, pH of plasma, and ATP and 2,3-DPG content of erythrocytes. The blood preserved in plastic bags showed less changes than blood in glass bottles. The presence of air or nitrogen gas in blood seems to increase the pH perhaps by elimination of carbon dioxide (CO2) which in turn causes the different rates of glycolysis in the erythrocytes.", "contents": "Physical and chemical changes of ACD-preserved blood: a comparison of blood in glass bottles and plastic bags. ACD blood was preserved in glass bottles with or without aeration and in plastic bags in air or nitrogen gas at 4.5 degrees C. The blood was examined for physical and chemical changes of erythrocyte membrane resistance, hemoglobin in the plasma, the viscosity of the blood, pH of plasma, and ATP and 2,3-DPG content of erythrocytes. The blood preserved in plastic bags showed less changes than blood in glass bottles. The presence of air or nitrogen gas in blood seems to increase the pH perhaps by elimination of carbon dioxide (CO2) which in turn causes the different rates of glycolysis in the erythrocytes."}
{"id": "PMID:9732", "title": "[Metabolic disorders in the acute stage of cardiac infarction].", "content": "The level of lactates and pyruvates in arterial blood of 35 patients with myocardial infarction without shock (17-without heart insufficiency and 18-with manifested but in various degrees) is higher as compared with the level of 18 healthy subject and the elevation is better manifested in the patients with cardiac insufficiency. The highest level of lactates and pyruvates is reached in the first 48 hours of the onset of the disease, after which they decrease progressively and  in patients without cardiac insufficiency is normalized by the 5-6th day and in those with insufficiency-remains elevated. Slight to moderate correlation exists between the level of lactates and BE and PaCO2. Lacate and pyruvate level reoresents a more sensitive index for the existence of distrubances in the tissue metabolism as compared with the indices of alkaline-acid equilibtrium.", "contents": "[Metabolic disorders in the acute stage of cardiac infarction]. The level of lactates and pyruvates in arterial blood of 35 patients with myocardial infarction without shock (17-without heart insufficiency and 18-with manifested but in various degrees) is higher as compared with the level of 18 healthy subject and the elevation is better manifested in the patients with cardiac insufficiency. The highest level of lactates and pyruvates is reached in the first 48 hours of the onset of the disease, after which they decrease progressively and  in patients without cardiac insufficiency is normalized by the 5-6th day and in those with insufficiency-remains elevated. Slight to moderate correlation exists between the level of lactates and BE and PaCO2. Lacate and pyruvate level reoresents a more sensitive index for the existence of distrubances in the tissue metabolism as compared with the indices of alkaline-acid equilibtrium."}
{"id": "PMID:9733", "title": "[Integrated stimulation test with releasing hormones on healthy men and on patients with various forms of male hypogonadism].", "content": "Ninety subjects were examined; 20 healthy males, 20 patients with primary hypogonadism, 30 patients with Klinefelter's syndrome and 20 patients with secondary hypogonadism. The stimulating test with 200 mug LH-RH and 200 mug TTH was carried out tp all subjects examined, applied in two successive o.v. injections. The plasma as regards the levels of TTH, prolactin, FSH, LH, ACTH and STH is investigated every 0,20, 30, 60 and 90 minutes. The levels of tbe mentioned hormones were determined as well as the normal respond reaction. The basic LH and FSH levels are considerabty elevated in patients with primary hypogonadism and Klinefelter's syndrome and the respond reaction to stimulation is normal or diminished. A strict correlation between the number of X chromosomes and the level of FSH and LH was established in the patients with Klinefelter's syndrome. With respect to TTH, the basic, level in patients with primary hypogonadism in normal in 13 patients and pathological deviations were found in 7 patients. A strict correlation between TTH level and the number of X-chromosomes exists, Prolactin level in both groups is decreased. In patients with secondary hypogonadism the basic level of LH and ESH is decreased or at the lower limits of the norm. The respond reaction is absent. Both TTH and prolactin levels are pathologically changed as well as the respond reactions to stimulation depending on the etiology of the primary endocrine distrubance that had led to hypoginadism development.", "contents": "[Integrated stimulation test with releasing hormones on healthy men and on patients with various forms of male hypogonadism]. Ninety subjects were examined; 20 healthy males, 20 patients with primary hypogonadism, 30 patients with Klinefelter's syndrome and 20 patients with secondary hypogonadism. The stimulating test with 200 mug LH-RH and 200 mug TTH was carried out tp all subjects examined, applied in two successive o.v. injections. The plasma as regards the levels of TTH, prolactin, FSH, LH, ACTH and STH is investigated every 0,20, 30, 60 and 90 minutes. The levels of tbe mentioned hormones were determined as well as the normal respond reaction. The basic LH and FSH levels are considerabty elevated in patients with primary hypogonadism and Klinefelter's syndrome and the respond reaction to stimulation is normal or diminished. A strict correlation between the number of X chromosomes and the level of FSH and LH was established in the patients with Klinefelter's syndrome. With respect to TTH, the basic, level in patients with primary hypogonadism in normal in 13 patients and pathological deviations were found in 7 patients. A strict correlation between TTH level and the number of X-chromosomes exists, Prolactin level in both groups is decreased. In patients with secondary hypogonadism the basic level of LH and ESH is decreased or at the lower limits of the norm. The respond reaction is absent. Both TTH and prolactin levels are pathologically changed as well as the respond reactions to stimulation depending on the etiology of the primary endocrine distrubance that had led to hypoginadism development."}
{"id": "PMID:9734", "title": "Effect of aqueous extract of Eugenia caryophyllus on brain acetylcholine esterase in rats.", "content": "The effect of aqueous extract of Eugenia caryophyllus on brain acetylcholine esterase (AChE) activity in rats was studied. Results indicate that the aqueous extract reduced the hydrolysis of acetylcholine (ACh) by AChE. This reducing effect was not due to the acidic nature of the extract and suggests that Eugenia caryophyllus contains some water soluble substance(s) with anti-choline esterase activity.", "contents": "Effect of aqueous extract of Eugenia caryophyllus on brain acetylcholine esterase in rats. The effect of aqueous extract of Eugenia caryophyllus on brain acetylcholine esterase (AChE) activity in rats was studied. Results indicate that the aqueous extract reduced the hydrolysis of acetylcholine (ACh) by AChE. This reducing effect was not due to the acidic nature of the extract and suggests that Eugenia caryophyllus contains some water soluble substance(s) with anti-choline esterase activity."}
{"id": "PMID:9742", "title": "Properties of proteolytic enzymes isolated from a thermophilic strain of Micromonospora vulgaris 42.", "content": "Two proteolytic enzymes, protease A and protease B, were isolated in homogeneous state from the cultural broth of the thermophilic actinomycete Micromonospora vulgaris 42. Their physicochemical properties were studied, i.e., molecular weight (50 000 for protease A and 30 000 for protease B), amino acid composition, N-terminal amino acids (phenylalanine for protease A and alanine for protease B). The specificity of the action of these enzymes was assayed by splitting the B chain of oxidized insulin. Both enzymes are neutral proteases of the thermolysine type.", "contents": "Properties of proteolytic enzymes isolated from a thermophilic strain of Micromonospora vulgaris 42. Two proteolytic enzymes, protease A and protease B, were isolated in homogeneous state from the cultural broth of the thermophilic actinomycete Micromonospora vulgaris 42. Their physicochemical properties were studied, i.e., molecular weight (50 000 for protease A and 30 000 for protease B), amino acid composition, N-terminal amino acids (phenylalanine for protease A and alanine for protease B). The specificity of the action of these enzymes was assayed by splitting the B chain of oxidized insulin. Both enzymes are neutral proteases of the thermolysine type."}
{"id": "PMID:9743", "title": "Histone-like protein fractions of Kluyveromyces fragilis and their relation to the cell cycle.", "content": "Protein fractions were obtained from Kluyveromyces fragilis by pH titration, a technique used for histone extraction, following the inclusion of a distilled water extraction stage, and the fractions partially characterized. The inclusion of a distilled water step resulted in a tenfold purification of the fraction obtained at pH 2.20 as compared with pH titration alone. In synchronous cultures induced with 2'-deoxyadenosine or prepared by selection this fraction displayed a stepwise accumulation, and doubled in quantity at a point about one third of a cycle after cell division. The fraction obtained at pH 1.35 resembled calf thymus f2a2 histone in its extraction properties and amino acid composition, and also showed a possible stepwise accumulation. Other fractions appear to accumulate exponentially.", "contents": "Histone-like protein fractions of Kluyveromyces fragilis and their relation to the cell cycle. Protein fractions were obtained from Kluyveromyces fragilis by pH titration, a technique used for histone extraction, following the inclusion of a distilled water extraction stage, and the fractions partially characterized. The inclusion of a distilled water step resulted in a tenfold purification of the fraction obtained at pH 2.20 as compared with pH titration alone. In synchronous cultures induced with 2'-deoxyadenosine or prepared by selection this fraction displayed a stepwise accumulation, and doubled in quantity at a point about one third of a cycle after cell division. The fraction obtained at pH 1.35 resembled calf thymus f2a2 histone in its extraction properties and amino acid composition, and also showed a possible stepwise accumulation. Other fractions appear to accumulate exponentially."}
{"id": "PMID:9747", "title": "[Malabsorption caused by HBsAg-positive panareteritis nodosa].", "content": "A 36 year old man with panarteriitis nodosa (PAN) presented over a certain period of time meinly with gastrointestinal symptoms. He was HBsAg positive and a \"reactive\" hepatitis with histologically demonstrated. Arterial microaneurysms and stenoses were detected by angiography in the liver, kidney and small intestine. These findings were confirmed by autopsy. Vascular occlusions had caused infarctions of the small intestine as well as necroses and ulcerations of the large bowel. Chronic ischemia is considered as cause of the patient's malabsorption-syndrome. It is suggested, that cachexia of PAN may be partly due to malabsorption.", "contents": "[Malabsorption caused by HBsAg-positive panareteritis nodosa]. A 36 year old man with panarteriitis nodosa (PAN) presented over a certain period of time meinly with gastrointestinal symptoms. He was HBsAg positive and a \"reactive\" hepatitis with histologically demonstrated. Arterial microaneurysms and stenoses were detected by angiography in the liver, kidney and small intestine. These findings were confirmed by autopsy. Vascular occlusions had caused infarctions of the small intestine as well as necroses and ulcerations of the large bowel. Chronic ischemia is considered as cause of the patient's malabsorption-syndrome. It is suggested, that cachexia of PAN may be partly due to malabsorption."}
{"id": "PMID:9754", "title": "[Maldescensus testis (author's transl)].", "content": "During the last years numerous publications about clinical, endocrinologic, histologic, and animal experimental examinations for maldescensus have been made intending to find the most favourable time of therapy for obtaining fertility later on. Since the results partially differ considerably and even the findings in their prospective meaning are not easy to interpret, the right time is still under dispute, particularly because it is hardly possible to determine the limitation of inborn dysgenesis against acquired degenerative changes caused by a dystop position. The unanimous opinion exists for the scrotal position of the testicles to be repaired at least until puberty.", "contents": "[Maldescensus testis (author's transl)]. During the last years numerous publications about clinical, endocrinologic, histologic, and animal experimental examinations for maldescensus have been made intending to find the most favourable time of therapy for obtaining fertility later on. Since the results partially differ considerably and even the findings in their prospective meaning are not easy to interpret, the right time is still under dispute, particularly because it is hardly possible to determine the limitation of inborn dysgenesis against acquired degenerative changes caused by a dystop position. The unanimous opinion exists for the scrotal position of the testicles to be repaired at least until puberty."}
{"id": "PMID:9756", "title": "[The transfer of drugs into the amniotic fluid].", "content": "On the basis of the present literature and our own results a review will be given about the importance of the physico-chemical properties of drugs and of different factors of biological system \"mother, fetus and amniotic fluid\" for the passage of drugs into amniotic fluid. The amniotic fluid is relieved as a possible distribution volume for drugs.", "contents": "[The transfer of drugs into the amniotic fluid]. On the basis of the present literature and our own results a review will be given about the importance of the physico-chemical properties of drugs and of different factors of biological system \"mother, fetus and amniotic fluid\" for the passage of drugs into amniotic fluid. The amniotic fluid is relieved as a possible distribution volume for drugs."}
{"id": "PMID:9757", "title": "Alkaline ribonuclease from rye germ cytosol.", "content": "1. Alkaline ribonuclease (pH optimum 7.6) was isolated from rye (Secale cereale L) germ cytosol and partially purified; the preparation was devoid of other nucleolytic activities. 2. The enzyme is a typical endonuclease hydrolysing all phosphodiester bonds in RNA, yielding ultimately purine and pyrimidine nucleoside 2',3'-cyclic phosphates and the corresponding 3'-phosphates. Upon extensive digestion of synthetic polyribonucleotides, pyrimidine, but not purine, nucleoside 3'-phosphates are formed. The enzyme does not hydrolyse synthetic purine cyclic nucleotides. 3. The enzyme does not depolymerize double-stranded complexes of poly(A) and poly(U). 4. Susceptibility to photooxidation and inhibition by 2-hydroxy-5-nitrobenzyl bromide and N-bromosuccinimide implies the involvement of tryptophan residue in the active centre of the enzyme.", "contents": "Alkaline ribonuclease from rye germ cytosol. 1. Alkaline ribonuclease (pH optimum 7.6) was isolated from rye (Secale cereale L) germ cytosol and partially purified; the preparation was devoid of other nucleolytic activities. 2. The enzyme is a typical endonuclease hydrolysing all phosphodiester bonds in RNA, yielding ultimately purine and pyrimidine nucleoside 2',3'-cyclic phosphates and the corresponding 3'-phosphates. Upon extensive digestion of synthetic polyribonucleotides, pyrimidine, but not purine, nucleoside 3'-phosphates are formed. The enzyme does not hydrolyse synthetic purine cyclic nucleotides. 3. The enzyme does not depolymerize double-stranded complexes of poly(A) and poly(U). 4. Susceptibility to photooxidation and inhibition by 2-hydroxy-5-nitrobenzyl bromide and N-bromosuccinimide implies the involvement of tryptophan residue in the active centre of the enzyme."}
{"id": "PMID:9752", "title": "[Fatal kidney diseases due to analogesic abuse in Switzerland].", "content": "As part of an investigation into death by poisoning in Switzerland we were able to examine the register of deaths at the Swiss Federal Bureau of Statistics. All the medical reports which named analgesic nephropathy as being the basic illness and the main cause of death have been taken into consideration in this work. 331 deaths occurred in the five year period 1967-1971, and were studied as closely as the documents allowed. The earliest cases of death arose in the thirties, the maximum number however occurring between the age of 60 and 70. Between the onset of kidney damage and the actual death elapses a period of about 10 years. The ratio from woman to man is almost 2,8:1. The occurrence is particularly frequent among childless housewives. The victims are people of widely different occupations and social classes. The analgesic nephropathy resulting from addiction and leading to death is most frequently encountered among the population of the cities, and the German Swiss Cantons, as well as among people of protestant faith. The shocking number of 331 deaths in five years (in 1973 there were a further 79 cases) bears witness to the need for adequate preventive measures.", "contents": "[Fatal kidney diseases due to analogesic abuse in Switzerland]. As part of an investigation into death by poisoning in Switzerland we were able to examine the register of deaths at the Swiss Federal Bureau of Statistics. All the medical reports which named analgesic nephropathy as being the basic illness and the main cause of death have been taken into consideration in this work. 331 deaths occurred in the five year period 1967-1971, and were studied as closely as the documents allowed. The earliest cases of death arose in the thirties, the maximum number however occurring between the age of 60 and 70. Between the onset of kidney damage and the actual death elapses a period of about 10 years. The ratio from woman to man is almost 2,8:1. The occurrence is particularly frequent among childless housewives. The victims are people of widely different occupations and social classes. The analgesic nephropathy resulting from addiction and leading to death is most frequently encountered among the population of the cities, and the German Swiss Cantons, as well as among people of protestant faith. The shocking number of 331 deaths in five years (in 1973 there were a further 79 cases) bears witness to the need for adequate preventive measures."}
{"id": "PMID:9758", "title": "Inhibition by alanine of AMP-deaminase from rabbit skeletal muscle.", "content": "1. Alanine inhibits rabbit muscle AMP-deaminase while aspartate, histidine and glutamate are ineffective. 2. The degree and type of inhibition of AMP-deaminase by alanine depend on pH; at pH 6.5 alanine behaves like an allosteric effector exerting a negative heterotropic effect. At pH 7.0 the inhibition is non-competitive, Ki being as high as 19 mM. 3. The probable significance of the effect of alanine on AMP-deaminase in muscle metabolism is discussed.", "contents": "Inhibition by alanine of AMP-deaminase from rabbit skeletal muscle. 1. Alanine inhibits rabbit muscle AMP-deaminase while aspartate, histidine and glutamate are ineffective. 2. The degree and type of inhibition of AMP-deaminase by alanine depend on pH; at pH 6.5 alanine behaves like an allosteric effector exerting a negative heterotropic effect. At pH 7.0 the inhibition is non-competitive, Ki being as high as 19 mM. 3. The probable significance of the effect of alanine on AMP-deaminase in muscle metabolism is discussed."}
{"id": "PMID:9753", "title": "[Drugs and their way of application in juvenile drug abuse. A dimension-analytical study of consumption habits].", "content": "In a sample of 382 heavy users mode and extent of drug abuse were inquired. Factor analysis of the data gave three factors named \"i.v. applicated illegal drugs\", \"oral applicated illegal drugs\" and \"oral applicated medicaments\" for short. Results show that attitudes of the drug users towards their drug uses are strongly influenced by the mode of application and the definitions of the drug laws, whereas pharmacological aspects and subjective effects have hardly any demonstrable importance.", "contents": "[Drugs and their way of application in juvenile drug abuse. A dimension-analytical study of consumption habits]. In a sample of 382 heavy users mode and extent of drug abuse were inquired. Factor analysis of the data gave three factors named \"i.v. applicated illegal drugs\", \"oral applicated illegal drugs\" and \"oral applicated medicaments\" for short. Results show that attitudes of the drug users towards their drug uses are strongly influenced by the mode of application and the definitions of the drug laws, whereas pharmacological aspects and subjective effects have hardly any demonstrable importance."}
{"id": "PMID:9759", "title": "Regulation of aconitate hydratase activity from rat kidney cortex by bicarbonate.", "content": "1. The increase in pH value and bicarbonate concentration stimulated citrate synthesis from pyruvate and malate, inhibiting simultaneously conversion of isocitrate to citrate. 2. Bicarbonate inhibited competitively the activity of aconitate hydratase, probably binding with the two active sites of the enzyme. The Ki values for the cytoplasmic and mitochondrial enzyme were, respectively, 27 and 38 mM. The pH optimum for both forms of the enzyme in Tris-HCl buffer was in the range 7.8-8.6, and in bicarbonate buffer varied from 7.2 to 8.0, depending on the form of the enzyme and the substrate used. 3. Only free, completely dissociated citrate anion acts as a substrate for aconitate hydratase. 4. The role of aconitate hydratase as a factor controlling the rate of citrate metabolism in kidney in metabolic alkalosis is discussed.", "contents": "Regulation of aconitate hydratase activity from rat kidney cortex by bicarbonate. 1. The increase in pH value and bicarbonate concentration stimulated citrate synthesis from pyruvate and malate, inhibiting simultaneously conversion of isocitrate to citrate. 2. Bicarbonate inhibited competitively the activity of aconitate hydratase, probably binding with the two active sites of the enzyme. The Ki values for the cytoplasmic and mitochondrial enzyme were, respectively, 27 and 38 mM. The pH optimum for both forms of the enzyme in Tris-HCl buffer was in the range 7.8-8.6, and in bicarbonate buffer varied from 7.2 to 8.0, depending on the form of the enzyme and the substrate used. 3. Only free, completely dissociated citrate anion acts as a substrate for aconitate hydratase. 4. The role of aconitate hydratase as a factor controlling the rate of citrate metabolism in kidney in metabolic alkalosis is discussed."}
{"id": "PMID:9760", "title": "Trypsin inhibitors in bovine lung and pancreas during development.", "content": "1. The activity of trypsin inhibitors in lung and pancreas increased with age of the animals. 2. In foetal lung the activity of the basic Kunitz-type inhibitor was 1% that, and in calf lung 5-30% that, found in adult animals. 3. In foetal pancreas the basic Kunitz-type inhibitor was not detected, and in calf pancreas its activity was much lower than in adult animals. The activity of the acidic Kazal-type inhibitor in foetal pancreas was significantly lower than in calf or adult animal.", "contents": "Trypsin inhibitors in bovine lung and pancreas during development. 1. The activity of trypsin inhibitors in lung and pancreas increased with age of the animals. 2. In foetal lung the activity of the basic Kunitz-type inhibitor was 1% that, and in calf lung 5-30% that, found in adult animals. 3. In foetal pancreas the basic Kunitz-type inhibitor was not detected, and in calf pancreas its activity was much lower than in adult animals. The activity of the acidic Kazal-type inhibitor in foetal pancreas was significantly lower than in calf or adult animal."}
{"id": "PMID:9761", "title": "Inhibition of Ca++-stimulated respiration by uncouplers.", "content": "In a phosphate medium at pH 6.6 low concentrations of uncouplers such as p-trifluoromethoxyphenylhydrazone carbonylcyanide and 2,4-dinitrophenol inhibit the oxidation of beta-hydroxybutyrate and succinate, when added during Ca++-accumulation. The inhibition depends on the amount of accumulated Ca++, and is released by N,N,N',N'-tetramethyl-p-phenylendiamine plus ascorbate as substrate. Under identical conditions the uncouplers have no inhibitory effect when added to mitochondria during state 3 respiration or during accumulation of Sr++. Inhibition of respiration by the decrease of transmembranal succinate transport or by accumulation of oxaloacetate can be excluded. It is suggested that accumulation of Ca++ in the presence of phosphate induces structural alteration of the mitochondrial membrane, which on the one hand changes the accessibility or sensitivity of dehydrogenases to uncouplers and causes leakage of accumulated Ca++ on the other.", "contents": "Inhibition of Ca++-stimulated respiration by uncouplers. In a phosphate medium at pH 6.6 low concentrations of uncouplers such as p-trifluoromethoxyphenylhydrazone carbonylcyanide and 2,4-dinitrophenol inhibit the oxidation of beta-hydroxybutyrate and succinate, when added during Ca++-accumulation. The inhibition depends on the amount of accumulated Ca++, and is released by N,N,N',N'-tetramethyl-p-phenylendiamine plus ascorbate as substrate. Under identical conditions the uncouplers have no inhibitory effect when added to mitochondria during state 3 respiration or during accumulation of Sr++. Inhibition of respiration by the decrease of transmembranal succinate transport or by accumulation of oxaloacetate can be excluded. It is suggested that accumulation of Ca++ in the presence of phosphate induces structural alteration of the mitochondrial membrane, which on the one hand changes the accessibility or sensitivity of dehydrogenases to uncouplers and causes leakage of accumulated Ca++ on the other."}
{"id": "PMID:9762", "title": "[Inhibition of the malic enzyme from Acinetobacter calcoaceticus by NADPH and NADH].", "content": "The malic enzyme enriched from Acinetobacter calcoaceticus is inhibited by NADPH and NADH. The inhibition afforded by the reduced coenzymes is not affected by NAD+, AMP and 3'.5'-AMP. Against L-malate, NADPH inhibits the enzyme in a noncompetitive linear fashion (Ki = 1.5 x 10(-4) M), against NADP+, competitively linearly (Ki = 5.0 x 10(-5) M). While NADPH acted as a product inhibitor, NADH seems to be an allosteric effector of the malic enzyme, because with L-malate as the variable substrate in the double reciprocal plot, a nonlinear curve is obtained.", "contents": "[Inhibition of the malic enzyme from Acinetobacter calcoaceticus by NADPH and NADH]. The malic enzyme enriched from Acinetobacter calcoaceticus is inhibited by NADPH and NADH. The inhibition afforded by the reduced coenzymes is not affected by NAD+, AMP and 3'.5'-AMP. Against L-malate, NADPH inhibits the enzyme in a noncompetitive linear fashion (Ki = 1.5 x 10(-4) M), against NADP+, competitively linearly (Ki = 5.0 x 10(-5) M). While NADPH acted as a product inhibitor, NADH seems to be an allosteric effector of the malic enzyme, because with L-malate as the variable substrate in the double reciprocal plot, a nonlinear curve is obtained."}
{"id": "PMID:9763", "title": "[Oxygen binding of hemoglobin following covalent fixation in the deoxy- and oxy- conformation].", "content": "Deoxyhemoglobin (deoxyHB) and oxyhemoglobin (HbO2) were covalently fixed to BrCN-activated Sephadex G-200. At pH 6, the oxygen semi-saturation pressure for the deoxyHb coupling product was 14.1, and for the HbO2 coupling product, 7.2 mm Hg. The alkaline Bohr effect delta was calculated to be - 0.55 and - 0.4 respectively. The Hill coefficients n are for both Hb derivatives between 1.4 and 1.5, independently of pH (for free Hb the respective values are pO2 50% = 18.2 mm Hg, delta = -0.55 and n = 2.5). Non-crosslinked dextran and Sephadex G-200 have no influence upon the affinity of free Hb to oxygen and upon cooperativity. As a reason for the varying oxygen-binding properties for the two Hb derivatives it is assumed that the amino group of valin alpha 1 is involved in the HbO2 fixation. In deoxyHb, this group is not probably converted. The reduced Hill coefficients and enhanced oxygen affinity are assumed to be due to impairment of the inter-chain contacts, to restrained cooperative mobility, and heterogeneity of the coupling products.", "contents": "[Oxygen binding of hemoglobin following covalent fixation in the deoxy- and oxy- conformation]. Deoxyhemoglobin (deoxyHB) and oxyhemoglobin (HbO2) were covalently fixed to BrCN-activated Sephadex G-200. At pH 6, the oxygen semi-saturation pressure for the deoxyHb coupling product was 14.1, and for the HbO2 coupling product, 7.2 mm Hg. The alkaline Bohr effect delta was calculated to be - 0.55 and - 0.4 respectively. The Hill coefficients n are for both Hb derivatives between 1.4 and 1.5, independently of pH (for free Hb the respective values are pO2 50% = 18.2 mm Hg, delta = -0.55 and n = 2.5). Non-crosslinked dextran and Sephadex G-200 have no influence upon the affinity of free Hb to oxygen and upon cooperativity. As a reason for the varying oxygen-binding properties for the two Hb derivatives it is assumed that the amino group of valin alpha 1 is involved in the HbO2 fixation. In deoxyHb, this group is not probably converted. The reduced Hill coefficients and enhanced oxygen affinity are assumed to be due to impairment of the inter-chain contacts, to restrained cooperative mobility, and heterogeneity of the coupling products."}
{"id": "PMID:9765", "title": "[Intracellular protein breakdown. VI. Isolation, properties and biological significance of cathepsin D from rat liver].", "content": "The preparation and properties of cathepsin D from rat liver are reported. The enzyme is an endopeptidase of lysosomal origin. The molecular weight was estimated to be 49000 by sodium-dodecylsulfate electrophoresis. We did not find any dissociation into subunits under reducing conditions, in contrast to some other authors. We found the enzyme to occur in at least 4 forms with the isoelectric points 5.87, 5.65, 5.41 and 5.13. Strong -SH-blocking reagents inhibit the activity, but the most powerful and specific inhibitor was pepstatin (Ki=38 nM). The substrate specificity is discussed. There was no proof for any zymogen activation in a great number of experiments. Since the cathepsins B1, B3 and L obviously seem to play the major role in the intracellular protein breakdown within the rat liver, the main task of cathepsin D is the degradation of extracellular proteins in this organ.", "contents": "[Intracellular protein breakdown. VI. Isolation, properties and biological significance of cathepsin D from rat liver]. The preparation and properties of cathepsin D from rat liver are reported. The enzyme is an endopeptidase of lysosomal origin. The molecular weight was estimated to be 49000 by sodium-dodecylsulfate electrophoresis. We did not find any dissociation into subunits under reducing conditions, in contrast to some other authors. We found the enzyme to occur in at least 4 forms with the isoelectric points 5.87, 5.65, 5.41 and 5.13. Strong -SH-blocking reagents inhibit the activity, but the most powerful and specific inhibitor was pepstatin (Ki=38 nM). The substrate specificity is discussed. There was no proof for any zymogen activation in a great number of experiments. Since the cathepsins B1, B3 and L obviously seem to play the major role in the intracellular protein breakdown within the rat liver, the main task of cathepsin D is the degradation of extracellular proteins in this organ."}
{"id": "PMID:9766", "title": "[Intracellular protein breakdown. VII. Cathepsin L and H; two new proteinases from rat liver lysosomes].", "content": "Some properties (molecular weight, pI, temperature stability, action of selected inhibitors, substrate specificity and pH-activity dependence) of two not yet known cathepsins from rat liver lysosomes are compared with the properties of the known cathepsin B1. Cathepsin L is a thiolproteinase, has a molecular weight of 23--24000 and a pI of 5,8--6,1. By disc electrophoresis and isoelectric focusing there appear several protein bands which all have enzymatic activity. Leupeptin behaves as a strong inhibitor. The pH-optimum for digestion of proteins is close to 5,0. Cathepsin L does not hydrolyse esters and splits synthetic low molecular substrates only to a low degree. Cathepsin L stored in presence of glutathion and EDTA in liquid nitrogen kept its activity for some months. Cathepsin H is an aminopeptidase as well as an endopeptidase. An enzyme with these bifunctional properties was detected up to now only in E. coli but not in animal cells. Cathepsin H is a thiol-enzyme with a molecular weight of 28000 and a pI of 7,1. Strong inhibitors are leucyl-chlormethan and SH-blocking substances. Leupeptin shows only a weak inhibitory effect to this enzyme compared to its action on cathepsins L and B1. The pH-optimum for hydrolysis of all substrates is 6.0. Cathepsin H splits proteins, amino acid derivatives and selected N-protected amino acid derivatives. Cathepsin H compared to cathepsin L and B1 is quite temperature stable.", "contents": "[Intracellular protein breakdown. VII. Cathepsin L and H; two new proteinases from rat liver lysosomes]. Some properties (molecular weight, pI, temperature stability, action of selected inhibitors, substrate specificity and pH-activity dependence) of two not yet known cathepsins from rat liver lysosomes are compared with the properties of the known cathepsin B1. Cathepsin L is a thiolproteinase, has a molecular weight of 23--24000 and a pI of 5,8--6,1. By disc electrophoresis and isoelectric focusing there appear several protein bands which all have enzymatic activity. Leupeptin behaves as a strong inhibitor. The pH-optimum for digestion of proteins is close to 5,0. Cathepsin L does not hydrolyse esters and splits synthetic low molecular substrates only to a low degree. Cathepsin L stored in presence of glutathion and EDTA in liquid nitrogen kept its activity for some months. Cathepsin H is an aminopeptidase as well as an endopeptidase. An enzyme with these bifunctional properties was detected up to now only in E. coli but not in animal cells. Cathepsin H is a thiol-enzyme with a molecular weight of 28000 and a pI of 7,1. Strong inhibitors are leucyl-chlormethan and SH-blocking substances. Leupeptin shows only a weak inhibitory effect to this enzyme compared to its action on cathepsins L and B1. The pH-optimum for hydrolysis of all substrates is 6.0. Cathepsin H splits proteins, amino acid derivatives and selected N-protected amino acid derivatives. Cathepsin H compared to cathepsin L and B1 is quite temperature stable."}
{"id": "PMID:9767", "title": "[Influence of glutathione on the catalytic properties of leucine aminopeptidase].", "content": "1. Leucine aminopeptidase does not catalyze the hydrolysis of glutathione. 2. Glutathione inhibits the hydrolysis of the substrates leucine hydrazide and leucine-p-nitroanilide by leucine aminopeptidase. 3. By means of kinetic experiments the type of the inhibition has been determined as noncompetitive. The inhibition constant Ki for the Mg2+-activated enzyme is five times higher than for the non-activated enzyme. 4. The degree of inhibition caused by glutathione depends on the pH value indicating a competition between glutathione and OH- ions. Mg2+-activated enzyme is invariably inhibited in the investigated pH range of 7.2 to 9.8. 5. A preincubation of the enzyme with glutathione changes the degree of activity enhancement by metal ions.", "contents": "[Influence of glutathione on the catalytic properties of leucine aminopeptidase]. 1. Leucine aminopeptidase does not catalyze the hydrolysis of glutathione. 2. Glutathione inhibits the hydrolysis of the substrates leucine hydrazide and leucine-p-nitroanilide by leucine aminopeptidase. 3. By means of kinetic experiments the type of the inhibition has been determined as noncompetitive. The inhibition constant Ki for the Mg2+-activated enzyme is five times higher than for the non-activated enzyme. 4. The degree of inhibition caused by glutathione depends on the pH value indicating a competition between glutathione and OH- ions. Mg2+-activated enzyme is invariably inhibited in the investigated pH range of 7.2 to 9.8. 5. A preincubation of the enzyme with glutathione changes the degree of activity enhancement by metal ions."}
{"id": "PMID:9768", "title": "Binding of tritiated methylated luteinizing hormone to bovine corpus luteum receptors.", "content": "The binding of luteinizing hormone (LH) to cow corpora lutea homogenates was studied using a tritium labelled hormone obtained by reductive methylation. The KD observed was 0.9 10(-10) M and the number of sites was the equivalent of 0.4 10(-15) moles per mg of wet tissue. The influence of the pH and temperature was examined. HCG and LH produced the same binding inhibition properties of the derivative used for labelling LH were similar to those of native LH. The inhibitory activity of the subunits was extremely low (alpha-LH: 4%, beta-LH: 1%). No significant inhibition was observed in the case of FSH or prolactin.", "contents": "Binding of tritiated methylated luteinizing hormone to bovine corpus luteum receptors. The binding of luteinizing hormone (LH) to cow corpora lutea homogenates was studied using a tritium labelled hormone obtained by reductive methylation. The KD observed was 0.9 10(-10) M and the number of sites was the equivalent of 0.4 10(-15) moles per mg of wet tissue. The influence of the pH and temperature was examined. HCG and LH produced the same binding inhibition properties of the derivative used for labelling LH were similar to those of native LH. The inhibitory activity of the subunits was extremely low (alpha-LH: 4%, beta-LH: 1%). No significant inhibition was observed in the case of FSH or prolactin."}
{"id": "PMID:9770", "title": "A descriptive and comparative study of oral health in 8-year-old Swedish children.", "content": "The aim of the study was to assess the oral health of a group of children, and to compare the findings with the results from an investigation performed 4 years earlier in children of the same age and living in the same area. The material consisted of 149 randomly selected 8-year-old children. The study included examination of caries and the state of the gingival conditions, enamel hypoplasia and opacities, supragingival calculus and extrinsic stains. Determinations were also made of the rate of secretion, pH and buffer effect of stimulated saliva. Socio-economic data and anamnestic dental data were noted. The investigation showed a decrease in caries frequency in the primary teeth, but not in the permanent teeth, during the four-year-period. As in the former investigation, regression analyses showed a negative correlation between the level of education of the parents and caries indices, and that the variation of the gingival indices could be explained by socio-economic factors. In addition, a negative correlation was found between the caries index for primary teeth and the rate of secretion of the saliva and the presence of supragingival calculus.", "contents": "A descriptive and comparative study of oral health in 8-year-old Swedish children. The aim of the study was to assess the oral health of a group of children, and to compare the findings with the results from an investigation performed 4 years earlier in children of the same age and living in the same area. The material consisted of 149 randomly selected 8-year-old children. The study included examination of caries and the state of the gingival conditions, enamel hypoplasia and opacities, supragingival calculus and extrinsic stains. Determinations were also made of the rate of secretion, pH and buffer effect of stimulated saliva. Socio-economic data and anamnestic dental data were noted. The investigation showed a decrease in caries frequency in the primary teeth, but not in the permanent teeth, during the four-year-period. As in the former investigation, regression analyses showed a negative correlation between the level of education of the parents and caries indices, and that the variation of the gingival indices could be explained by socio-economic factors. In addition, a negative correlation was found between the caries index for primary teeth and the rate of secretion of the saliva and the presence of supragingival calculus."}
{"id": "PMID:9771", "title": "Inorganic pyrophosphatase in isolated enamel organ and odontoblasts from the rat incisor.", "content": "The inorganic pyrophosphatase (PPiase) activity was determined by a colorimetric method in the odontoblasts and the parts of the enamel organ related to enamel matrix formation and enamel maturation. The effects on PPi hydrolysis by EDTA, R 8231, urea and heat treatment were found to be almost identical to those reported for nonspecific alkaline phosphatase (APase) in the same tissues. The Mg2+ activation curve for PPiase was also similar. Like those of APase, these characteristics of PPiase activity were identical in the three locations studied. It is suggested that the close similarity in the properties of PPiase and APase is due to activity of the same enzyme, a concept which is in agreement with recent biochemical and histochemical studies of calcification.", "contents": "Inorganic pyrophosphatase in isolated enamel organ and odontoblasts from the rat incisor. The inorganic pyrophosphatase (PPiase) activity was determined by a colorimetric method in the odontoblasts and the parts of the enamel organ related to enamel matrix formation and enamel maturation. The effects on PPi hydrolysis by EDTA, R 8231, urea and heat treatment were found to be almost identical to those reported for nonspecific alkaline phosphatase (APase) in the same tissues. The Mg2+ activation curve for PPiase was also similar. Like those of APase, these characteristics of PPiase activity were identical in the three locations studied. It is suggested that the close similarity in the properties of PPiase and APase is due to activity of the same enzyme, a concept which is in agreement with recent biochemical and histochemical studies of calcification."}
{"id": "PMID:9772", "title": "Dissolution rate of cadmium from dental gold solder alloys.", "content": "The dissolution rate of cadmium from six different dental gold solder alloys was determined in an in vitro potentiostatic study. The measurements were made in the potential range 740--880 mV and attempts have been made to extrapolate the results to a potential region that might in reality occur in the oral cavity. For comparison the dissolution rates of copper and zinc were also determined. Electrochemically the most interesting quantity was the logarithm of the dissolution rate because it is a linear function of the applied potential. This linear relationship was given by the Tafel equation. The dissolution rate of cadmium was shown to be rather small even under circumstances which may be said to represent very unfavourable conditions within the oral cavity.", "contents": "Dissolution rate of cadmium from dental gold solder alloys. The dissolution rate of cadmium from six different dental gold solder alloys was determined in an in vitro potentiostatic study. The measurements were made in the potential range 740--880 mV and attempts have been made to extrapolate the results to a potential region that might in reality occur in the oral cavity. For comparison the dissolution rates of copper and zinc were also determined. Electrochemically the most interesting quantity was the logarithm of the dissolution rate because it is a linear function of the applied potential. This linear relationship was given by the Tafel equation. The dissolution rate of cadmium was shown to be rather small even under circumstances which may be said to represent very unfavourable conditions within the oral cavity."}
{"id": "PMID:9769", "title": "Preliminary report: parenteral Lorazepam in induced epileptic states in man.", "content": "The anticonvulsive effect of Lorazepam -- one of the newer diazepines -- has been tested in 10 patients with induced epileptic conditions under continuous polygraphic control. The quantitative analysis of the paroxysmal discharges -- i.e. the evolution of the \"paroxysmal index\" -- shows that 5 mg IV Lorazepam normalize the tracings in 2.3 minutes. Parenteral Lorazepam inhibits pharmacologically-induced electroencephalographic abnormalities in man. Its action is slightly delayed. No effect on cardiac or respiratory function, or muscle tone was noted.", "contents": "Preliminary report: parenteral Lorazepam in induced epileptic states in man. The anticonvulsive effect of Lorazepam -- one of the newer diazepines -- has been tested in 10 patients with induced epileptic conditions under continuous polygraphic control. The quantitative analysis of the paroxysmal discharges -- i.e. the evolution of the \"paroxysmal index\" -- shows that 5 mg IV Lorazepam normalize the tracings in 2.3 minutes. Parenteral Lorazepam inhibits pharmacologically-induced electroencephalographic abnormalities in man. Its action is slightly delayed. No effect on cardiac or respiratory function, or muscle tone was noted."}
{"id": "PMID:9773", "title": "The correlation between salivary peroxidase activity, salivary flow rate, and the oxidation-reduction potentials of human saliva and dental plaque suspensions.", "content": "18 subjects, 9 males and 9 females, were examined regarding salivary oxidation-reduction potential, salivary flow rate, salivary peroxidase activity, oxidation-reduction potential of dental plaque samples, and dental health. Both the peroxidase activity, expressed as the salivary lactoperoxidase, and the salivary oxidation-reduction potential increased with increasing salivary flow rate. The variation of these variables was obviously due to changes in salivary flow rate during the day. The remarkably slight differences in peroxidase activities, oxidation-reduction potentials and salivary flow rate in this study did not have any marked correlation with the clinical recordings of the test groups.", "contents": "The correlation between salivary peroxidase activity, salivary flow rate, and the oxidation-reduction potentials of human saliva and dental plaque suspensions. 18 subjects, 9 males and 9 females, were examined regarding salivary oxidation-reduction potential, salivary flow rate, salivary peroxidase activity, oxidation-reduction potential of dental plaque samples, and dental health. Both the peroxidase activity, expressed as the salivary lactoperoxidase, and the salivary oxidation-reduction potential increased with increasing salivary flow rate. The variation of these variables was obviously due to changes in salivary flow rate during the day. The remarkably slight differences in peroxidase activities, oxidation-reduction potentials and salivary flow rate in this study did not have any marked correlation with the clinical recordings of the test groups."}
{"id": "PMID:9774", "title": "Rapid diagnosis of Enterobacteriaceae. I. Detection of bacterial glycosidases.", "content": "The paper describes a number of tests for the rapid detection of glycosidases including alpha-glucosidase, beta-glucosidase, beta-glucuronidase, beta-xylosidase and alpha-fucosidase. The methods use heavy suspensions of viable but non-multiplying bacteria in a buffered solution of a chromogenic substrate. The results of the tests are readable within 4 h. The application of these tests to a collection of 633 strains of Enterobacteriaceae and Vibrionaceae demonstrates that some of the tests may be valuable additions to the present tests available for the identification of bacteria belonging to these families. beta-glucuronidase activity was observed only in strains of the Escherichia-Shigella group. 97 per cent of the Escherichia strains possessed beta-glucuronidase activity. beta-xylosidase activity was almost completely restricted to strains of the Klebsiella-Enterobacter group in addition to Yersinia strains. None of the strains possessed alpha-fucosidase activity.", "contents": "Rapid diagnosis of Enterobacteriaceae. I. Detection of bacterial glycosidases. The paper describes a number of tests for the rapid detection of glycosidases including alpha-glucosidase, beta-glucosidase, beta-glucuronidase, beta-xylosidase and alpha-fucosidase. The methods use heavy suspensions of viable but non-multiplying bacteria in a buffered solution of a chromogenic substrate. The results of the tests are readable within 4 h. The application of these tests to a collection of 633 strains of Enterobacteriaceae and Vibrionaceae demonstrates that some of the tests may be valuable additions to the present tests available for the identification of bacteria belonging to these families. beta-glucuronidase activity was observed only in strains of the Escherichia-Shigella group. 97 per cent of the Escherichia strains possessed beta-glucuronidase activity. beta-xylosidase activity was almost completely restricted to strains of the Klebsiella-Enterobacter group in addition to Yersinia strains. None of the strains possessed alpha-fucosidase activity."}
{"id": "PMID:9775", "title": "Proteolytic degradation of staphylococcal alpha-toxin.", "content": "Staphylococcal alpha-toxin of mol.wt. 39,000 was degraded at an alkaline pH by staphylococcal extracellular proteases resulting in the formation of three relatively stable intermediates with mol.wt. 27,500, 23,500 and 12,000. The intermediate with mol.wt. 27,500 which existed in two charged forms, was isolated by column chromatography and found to be non-haemolytic. Furthermore, it could be obtained by proteolysis of alpha-toxin (mol.wt. 39,000) with chymotrypsin in low concentrations. This intermediate was further degraded by trypsin to the protein with mol.wt. 23,500 and 12,000.", "contents": "Proteolytic degradation of staphylococcal alpha-toxin. Staphylococcal alpha-toxin of mol.wt. 39,000 was degraded at an alkaline pH by staphylococcal extracellular proteases resulting in the formation of three relatively stable intermediates with mol.wt. 27,500, 23,500 and 12,000. The intermediate with mol.wt. 27,500 which existed in two charged forms, was isolated by column chromatography and found to be non-haemolytic. Furthermore, it could be obtained by proteolysis of alpha-toxin (mol.wt. 39,000) with chymotrypsin in low concentrations. This intermediate was further degraded by trypsin to the protein with mol.wt. 23,500 and 12,000."}
{"id": "PMID:9776", "title": "Glycerol transport in human red cells.", "content": "The kinetics of 14C-glycerol exchange was studied in human red cells. Glycerol appeared to be transported by two mechanisms: (i) by facilitated diffusion with permeability depending on glycerol concentration, and (ii) by an unspecific pathway, presumably representing the diffusion of individual glycerol molecules through the membrane with permeability independent of glycerol concentration. The latter permeability was 8 X 10(-8) cm/s at 20 degrees C, it was independent of pH, and had an activation energy of 25 kcal/mol. The facilitated transport of glycerol was completely inhibited by Cu++, and the activation energy was low, about 10 kcal/mol. The transport system was competitively inhibited by H+, reacting with at least three hydrogen analogue, as well as dimethylsulfoxide (a hydrogen bonding molecule with no structural resemblance to glycerol), inhibited glycerol transport competitively. Steins \"dimerizer hypothesis\" was revised according to our findings. A kinetic scheme describing the reactions of a transport controlling site with glycerol is presented in the Appendix. It is demonstrated in the article that the scheme accounts for out experimental results.", "contents": "Glycerol transport in human red cells. The kinetics of 14C-glycerol exchange was studied in human red cells. Glycerol appeared to be transported by two mechanisms: (i) by facilitated diffusion with permeability depending on glycerol concentration, and (ii) by an unspecific pathway, presumably representing the diffusion of individual glycerol molecules through the membrane with permeability independent of glycerol concentration. The latter permeability was 8 X 10(-8) cm/s at 20 degrees C, it was independent of pH, and had an activation energy of 25 kcal/mol. The facilitated transport of glycerol was completely inhibited by Cu++, and the activation energy was low, about 10 kcal/mol. The transport system was competitively inhibited by H+, reacting with at least three hydrogen analogue, as well as dimethylsulfoxide (a hydrogen bonding molecule with no structural resemblance to glycerol), inhibited glycerol transport competitively. Steins \"dimerizer hypothesis\" was revised according to our findings. A kinetic scheme describing the reactions of a transport controlling site with glycerol is presented in the Appendix. It is demonstrated in the article that the scheme accounts for out experimental results."}
{"id": "PMID:9777", "title": "Significance of the extracellular bicarbonate buffer system to anaerobic glycolysis in hypoxic muscle.", "content": "1. The influence of the carbon dioxide-bicarbonate buffer system on anaerobic energy production during severe hypoxia was studied in isolated right hemidiaphragms of rats.--2. When the tissue was incubated in a Ringer solution containing 25 mM HCO-3 aerated with 7% CO2 in N2 at pH 7.4, the lactate production and lactate content of the tissue increased.--3. At an extracellular (tissue bath) pH OF 6.9 the lactate production was stimulated when carbon dioxide and bicarbonate were changed to 19% and 25 mM, respectively. This stimulatory effect disappeared when these values were lowered to 7% and 7 mM.--4. At pH 7.4 the stimulatory effect of the carbon dioxide-bicarbonate system persisted when the buffer value was lowered from 60 to 3 mM by changing the system from an open (i.e. continuous gas equilibration) to a closed one (i.e. without any gas phase). Decreasing the glucose in the media from 22 to 0 mM reduced the lactate production and abolished the stimulatory effect of the carbon dioxide--bicarbonate system.--5. There was no direct effect of this system on the glycolytic enzymes (i.e. lactate production and activity of phosphofructokinase of homogenates).", "contents": "Significance of the extracellular bicarbonate buffer system to anaerobic glycolysis in hypoxic muscle. 1. The influence of the carbon dioxide-bicarbonate buffer system on anaerobic energy production during severe hypoxia was studied in isolated right hemidiaphragms of rats.--2. When the tissue was incubated in a Ringer solution containing 25 mM HCO-3 aerated with 7% CO2 in N2 at pH 7.4, the lactate production and lactate content of the tissue increased.--3. At an extracellular (tissue bath) pH OF 6.9 the lactate production was stimulated when carbon dioxide and bicarbonate were changed to 19% and 25 mM, respectively. This stimulatory effect disappeared when these values were lowered to 7% and 7 mM.--4. At pH 7.4 the stimulatory effect of the carbon dioxide-bicarbonate system persisted when the buffer value was lowered from 60 to 3 mM by changing the system from an open (i.e. continuous gas equilibration) to a closed one (i.e. without any gas phase). Decreasing the glucose in the media from 22 to 0 mM reduced the lactate production and abolished the stimulatory effect of the carbon dioxide--bicarbonate system.--5. There was no direct effect of this system on the glycolytic enzymes (i.e. lactate production and activity of phosphofructokinase of homogenates)."}
{"id": "PMID:9778", "title": "Influence of adipose tissue blood flow on the lipolytic response to circulating noradrenaline at normal and reduced pH.", "content": "Hypercapnic acidosis (pH 7.0) inhibits the lipolytic response of canine subcutaneous adipose tissue to i.v. infused noradrenaline (NA) by 80 per cent or more. The response to sympathetic nerve stimulation, on the other hand, is only reduced by 10-40 per cent during acidosis. The fate of intravenously infused 3H-labelled NA (0.35 ug X kg-1 X min-1 for 30 min) was not significantly altered by acidosis. The rate of disappearance of unmetabolized NA from the arterial plasma after an infusion was the same at pH 7.4 and 7.0 and the calculated increase in circulating NA during infusions was 4 ng/ml at both pH:s. I.v. infusion of Na increases adipose tissue blood flow, an effect which is attenuated by acidosis. There was a significant correlation (p less than 0.001) between adipose tissue blood flow and the lipolytic response at normal pH. Preventing the NA-induced increase in blood flow by constant flow perfusion reduced the lipolytic response at normal pH. The degree of inhibition by acidosis of the lipolytic response to i.v. NA was significantly reduced (from 79 to 56 per cent, p less than 0.05) when the adipose tissue was perfused at constant flow. These data suggest that adipose tissue blood flow is important in determining the lipolytic response to i.v. NA, probably by influencing the delivery of NA to the tissue. The marked inhibition by acidosis of lipolysis due to i.v. infused NA therefore appears to be the combined effect of a direct antilipolytic effect of acidosis and a decreased delivery of NA to the adipose tissue due to the attenuated blood flow response.", "contents": "Influence of adipose tissue blood flow on the lipolytic response to circulating noradrenaline at normal and reduced pH. Hypercapnic acidosis (pH 7.0) inhibits the lipolytic response of canine subcutaneous adipose tissue to i.v. infused noradrenaline (NA) by 80 per cent or more. The response to sympathetic nerve stimulation, on the other hand, is only reduced by 10-40 per cent during acidosis. The fate of intravenously infused 3H-labelled NA (0.35 ug X kg-1 X min-1 for 30 min) was not significantly altered by acidosis. The rate of disappearance of unmetabolized NA from the arterial plasma after an infusion was the same at pH 7.4 and 7.0 and the calculated increase in circulating NA during infusions was 4 ng/ml at both pH:s. I.v. infusion of Na increases adipose tissue blood flow, an effect which is attenuated by acidosis. There was a significant correlation (p less than 0.001) between adipose tissue blood flow and the lipolytic response at normal pH. Preventing the NA-induced increase in blood flow by constant flow perfusion reduced the lipolytic response at normal pH. The degree of inhibition by acidosis of the lipolytic response to i.v. NA was significantly reduced (from 79 to 56 per cent, p less than 0.05) when the adipose tissue was perfused at constant flow. These data suggest that adipose tissue blood flow is important in determining the lipolytic response to i.v. NA, probably by influencing the delivery of NA to the tissue. The marked inhibition by acidosis of lipolysis due to i.v. infused NA therefore appears to be the combined effect of a direct antilipolytic effect of acidosis and a decreased delivery of NA to the adipose tissue due to the attenuated blood flow response."}
{"id": "PMID:9779", "title": "Contrast media with and without calcium for cardioangiography in children.", "content": "The possible beneficial effects of added calcium ions to contrast media to diminish myocardial toxicity was evaluated in 93 cardiac catheterizations with cardioangiography, performed in 50 children and adolescents. Two contrast media with equal iodine content (370 mg/ml) and similar physical properties were used: Isopawue-370, containing 0.34 mg calcium/ml, and Renografin-76, not containing calcium. It is concluded that addition of calcium to contrast media for cardioangiography in children and adolescents does not alter their myocardial, fluid or electrolyte effects when injected selectively into the cardiac chambers or great vessels.", "contents": "Contrast media with and without calcium for cardioangiography in children. The possible beneficial effects of added calcium ions to contrast media to diminish myocardial toxicity was evaluated in 93 cardiac catheterizations with cardioangiography, performed in 50 children and adolescents. Two contrast media with equal iodine content (370 mg/ml) and similar physical properties were used: Isopawue-370, containing 0.34 mg calcium/ml, and Renografin-76, not containing calcium. It is concluded that addition of calcium to contrast media for cardioangiography in children and adolescents does not alter their myocardial, fluid or electrolyte effects when injected selectively into the cardiac chambers or great vessels."}
{"id": "PMID:9780", "title": "Influence of the cation on the side-effects of urographic contrast media.", "content": "The incidence of side-effects produced by meglumine diatrizoate and meglumine-, meglumine-calcium-, and sodium-calcium-magnesium metrizoate, was compared in 800 urographies. Patients older than 60 years seem to have less side-effects than younger patients. The incidence of sensation of warmth seems to be higher in patients who have had previous urographies, compared to those who are examined for the first time. The incidence of this effect is higher for the sodium-calcium-magnesium salt of metrizoate, than for other salts of metrizoate.", "contents": "Influence of the cation on the side-effects of urographic contrast media. The incidence of side-effects produced by meglumine diatrizoate and meglumine-, meglumine-calcium-, and sodium-calcium-magnesium metrizoate, was compared in 800 urographies. Patients older than 60 years seem to have less side-effects than younger patients. The incidence of sensation of warmth seems to be higher in patients who have had previous urographies, compared to those who are examined for the first time. The incidence of this effect is higher for the sodium-calcium-magnesium salt of metrizoate, than for other salts of metrizoate."}
{"id": "PMID:9781", "title": "Regulation of lysine biosynthesis in Escherichia coli K12.", "content": "A general survey of the regulation in lysine biosynthesis in Escherichia coli K12 is presented. No polygenic operon exists for the genes that code for enzymes of the lysine biosynthetic pathway. Lysyl-tRNA is not directly involved as a co-repressor in the pathway. Different regulation mechanisms must exist for the different enzymes. In the case of the last enzyme, diaminopimelate decarboxylase, its synthesis is induced in vivo by the lysine-sensitive aspartokinase under its non-inhibited allosteric conformation.", "contents": "Regulation of lysine biosynthesis in Escherichia coli K12. A general survey of the regulation in lysine biosynthesis in Escherichia coli K12 is presented. No polygenic operon exists for the genes that code for enzymes of the lysine biosynthetic pathway. Lysyl-tRNA is not directly involved as a co-repressor in the pathway. Different regulation mechanisms must exist for the different enzymes. In the case of the last enzyme, diaminopimelate decarboxylase, its synthesis is induced in vivo by the lysine-sensitive aspartokinase under its non-inhibited allosteric conformation."}
{"id": "PMID:9783", "title": "Regulation of tyrosine and phenylalanine biosynthesis in Salmonella.", "content": "Several types of 4-fluorophenylalanine resistant mutants were isolated. In one type of mutant DAHP synthetase (tyr) and prephenate dehydrogenase were coordinately derepressed. The mutation was linked to aroF and tyrA and was cis- dominant by merodiploid analysis, thus confirming that it is an operator constitutive mutation (tyrOc). A second type of mutation showed highly elevated levels of tyrosine pathway enzymes which were not repressed by L-tyrosine. It was unlinked to tyrA and aroF, and was trans-recessive in merodiploids. These properties were attributed to a mutation in a regulator gene, tyrR (linked to pyr F), that resulted in altered or non-functional aporepressor. Hence tyrO, tyrA, and aroF constitute an operon regulated by tyrR. In a third type of mutation chorismate mutase P-prephenate dehydratase was highly elevated. It was not linked to pheA, was located in the 95--100 min region of the Salmonella chromosome, and was recessive to the wild type gene in merodiploids. A mutation was, therefore, indicated in a regulatory gene, pheR, which specified an aporepressor for regulating pheA. DAHP synthetase (phe), specified by aroG, was not regulated by pheR, but was derepressed in one of the tyrR mutants, suggesting that as in Escherichia coli tyrR may regulate DAHP synthetase(phe) and DAHP synthetase (tyr) with the same aporepressor. A novel mutation in chorismate mutase is described.", "contents": "Regulation of tyrosine and phenylalanine biosynthesis in Salmonella. Several types of 4-fluorophenylalanine resistant mutants were isolated. In one type of mutant DAHP synthetase (tyr) and prephenate dehydrogenase were coordinately derepressed. The mutation was linked to aroF and tyrA and was cis- dominant by merodiploid analysis, thus confirming that it is an operator constitutive mutation (tyrOc). A second type of mutation showed highly elevated levels of tyrosine pathway enzymes which were not repressed by L-tyrosine. It was unlinked to tyrA and aroF, and was trans-recessive in merodiploids. These properties were attributed to a mutation in a regulator gene, tyrR (linked to pyr F), that resulted in altered or non-functional aporepressor. Hence tyrO, tyrA, and aroF constitute an operon regulated by tyrR. In a third type of mutation chorismate mutase P-prephenate dehydratase was highly elevated. It was not linked to pheA, was located in the 95--100 min region of the Salmonella chromosome, and was recessive to the wild type gene in merodiploids. A mutation was, therefore, indicated in a regulatory gene, pheR, which specified an aporepressor for regulating pheA. DAHP synthetase (phe), specified by aroG, was not regulated by pheR, but was derepressed in one of the tyrR mutants, suggesting that as in Escherichia coli tyrR may regulate DAHP synthetase(phe) and DAHP synthetase (tyr) with the same aporepressor. A novel mutation in chorismate mutase is described."}
{"id": "PMID:9794", "title": "Blocking of olive oil induced plasma protein escape from the intestinal circulation by histamine antagonists and by a diamine oxidase releasing agent.", "content": "Earlier studies have shown that feeding of olive oil to rats substantially increased the plasma protein in the intestinal lymph. The possibility of histamine mediating this response was examined. The plasma protein escape from intestinal circulation after olive oil feeding was measured in rats in terms of the amount of Evans Blue labelled plasma protein found in the intestinal lymph. Animals treated with histamine antagonists (H1-receptor antagonist pyrilamine, 16-22 mg/kg i.p., plus H2-receptor antagonist Burimamide, 12-16 mg/kg i.p.) did not show an increase in the quantity of lymphatic plasma protein. Heparin pretreatment which releases the histaminolytic enzyme, diamine oxidase, into the interstitial space also prevented the increased accumulation of labelled plasma protein in the lymph after olive oil ingestion. Based on these observations, histamine appears to act on the intestinal microcirculation during olive oil absorption and allows larger quantities of plasma proteins to leave the intestinal circulation.", "contents": "Blocking of olive oil induced plasma protein escape from the intestinal circulation by histamine antagonists and by a diamine oxidase releasing agent. Earlier studies have shown that feeding of olive oil to rats substantially increased the plasma protein in the intestinal lymph. The possibility of histamine mediating this response was examined. The plasma protein escape from intestinal circulation after olive oil feeding was measured in rats in terms of the amount of Evans Blue labelled plasma protein found in the intestinal lymph. Animals treated with histamine antagonists (H1-receptor antagonist pyrilamine, 16-22 mg/kg i.p., plus H2-receptor antagonist Burimamide, 12-16 mg/kg i.p.) did not show an increase in the quantity of lymphatic plasma protein. Heparin pretreatment which releases the histaminolytic enzyme, diamine oxidase, into the interstitial space also prevented the increased accumulation of labelled plasma protein in the lymph after olive oil ingestion. Based on these observations, histamine appears to act on the intestinal microcirculation during olive oil absorption and allows larger quantities of plasma proteins to leave the intestinal circulation."}
{"id": "PMID:9796", "title": "Composition of the Zaysan virion.", "content": "The sedimentation coefficient of Zaysan virion ribonucleic acid (RNA), estimated by sucrose density gradient centrifugation, was 42 S. Pancreatic ribonuclease digested the viral RNA to acid-soluble fragments. Two viral structural proteins with apparent molecular weight of 50,000 and 30,000 daltons were identified by polyacrylamide gel electrophoresis. A dense, RNA-rich particle, containing the smaller polypeptide, was isolated after mild detergent treatment of Zaysan virus.", "contents": "Composition of the Zaysan virion. The sedimentation coefficient of Zaysan virion ribonucleic acid (RNA), estimated by sucrose density gradient centrifugation, was 42 S. Pancreatic ribonuclease digested the viral RNA to acid-soluble fragments. Two viral structural proteins with apparent molecular weight of 50,000 and 30,000 daltons were identified by polyacrylamide gel electrophoresis. A dense, RNA-rich particle, containing the smaller polypeptide, was isolated after mild detergent treatment of Zaysan virus."}
{"id": "PMID:9797", "title": "Morphological, cytological and biological observations on viruses isolated from patients with subacute thyroiditis de Quervain.", "content": "New data on viruses isolated from patients with subacute thyroiditis de Quervain are reported. Characteristic morphological, cytological, some physico-chemical and biological features of the isolated viruses are described. A possible role of these viruses in human and animal health disorders is discussed. The isolated viruses remain unclassified so far.", "contents": "Morphological, cytological and biological observations on viruses isolated from patients with subacute thyroiditis de Quervain. New data on viruses isolated from patients with subacute thyroiditis de Quervain are reported. Characteristic morphological, cytological, some physico-chemical and biological features of the isolated viruses are described. A possible role of these viruses in human and animal health disorders is discussed. The isolated viruses remain unclassified so far."}
{"id": "PMID:9798", "title": "Interfering activity of virulent and attenuated influenza virus strains.", "content": "The interfering activity of influenza virus variants A/Hong Kong/1/68 (H3N202), A/Victoria/35/72(H3N2-3), B/14/55 and B/USSR/69 differing in the level of their reactogenicity for adults and children was studied. An inverse relationship was established between reactogenicity of the strains and their interfering activity in the resistant chick embryo cell (CEC) cultures. Virulent strains did not interfere with vesicular stomatitis virus. Vaccine strains used for commercial live influenza vaccine safe for adults but reactogenic in children were intermediate and showed moderate interfering activity. The highest capacity for interference was demonstrated in cold-adapted thermosensitive variants non-pathogenic for both adults and children. The interfering activity of the attenuated strains increased progressively with increasing inocula.", "contents": "Interfering activity of virulent and attenuated influenza virus strains. The interfering activity of influenza virus variants A/Hong Kong/1/68 (H3N202), A/Victoria/35/72(H3N2-3), B/14/55 and B/USSR/69 differing in the level of their reactogenicity for adults and children was studied. An inverse relationship was established between reactogenicity of the strains and their interfering activity in the resistant chick embryo cell (CEC) cultures. Virulent strains did not interfere with vesicular stomatitis virus. Vaccine strains used for commercial live influenza vaccine safe for adults but reactogenic in children were intermediate and showed moderate interfering activity. The highest capacity for interference was demonstrated in cold-adapted thermosensitive variants non-pathogenic for both adults and children. The interfering activity of the attenuated strains increased progressively with increasing inocula."}
{"id": "PMID:9799", "title": "Interference stimulated by tick-borne encephalitis virus: influence of divalent cations.", "content": "The effects of divalent cations (barium, cobalt, calcium, copper, magnesium, zinc and iron) on the interference of tick-borne encephalitis (TE) virus with vaccinia virus in Detroit-6 cell cultures were investigated. An increase in interference was shown in the presence of cobalt, zinc, copper, and magnesium. Barium and iron displayed a marked inhibitory action. But an increase in interference was not parallel with an increased production of interferon.", "contents": "Interference stimulated by tick-borne encephalitis virus: influence of divalent cations. The effects of divalent cations (barium, cobalt, calcium, copper, magnesium, zinc and iron) on the interference of tick-borne encephalitis (TE) virus with vaccinia virus in Detroit-6 cell cultures were investigated. An increase in interference was shown in the presence of cobalt, zinc, copper, and magnesium. Barium and iron displayed a marked inhibitory action. But an increase in interference was not parallel with an increased production of interferon."}
{"id": "PMID:9800", "title": "Autoantibodies in sera of influenza patients.", "content": "Sera of the influenza patients and healthy controls were tested for some types of autoantibody (SMA, ANA, ABBA, AMA). They were detected in 83.8% of the patients' sera and in 16.6% of controls. SMA were present in 77.4%, ANA in 54.8%, and ABBA in 16.1% of the patient's sera. AMA were not detected. A majority of the sera contained more than one autoantibody type. The possible mechanisms of induction of the autoantibodies in virus infection and their possible role in disease are briefly discussed.", "contents": "Autoantibodies in sera of influenza patients. Sera of the influenza patients and healthy controls were tested for some types of autoantibody (SMA, ANA, ABBA, AMA). They were detected in 83.8% of the patients' sera and in 16.6% of controls. SMA were present in 77.4%, ANA in 54.8%, and ABBA in 16.1% of the patient's sera. AMA were not detected. A majority of the sera contained more than one autoantibody type. The possible mechanisms of induction of the autoantibodies in virus infection and their possible role in disease are briefly discussed."}
{"id": "PMID:9801", "title": "Latent pseudorabies virus infection in pigs.", "content": "Latent infection with the TOP strain of pseudorabies virus (PRV) was established in 6 weeks old piglets. Infectious virus was found in oropharyngeal swabs till day 10 post infection (p.i.); later on, attempts to detect the virus remained unsuccessful. However, PRV could be isolated by explantation of tonsils, cervical lymph nodes, nasal mucosa and gasserian ganglia. These tissues were removed between 160 and 181 days p.i., during cultivation, infectious PRV was released into the culture fluid from the 3rd to the 11th day of the explantation. PRV antigen was seen by immunofluorescence only in explants coming from gasserian ganglia. It was localized in both neurons and satellite cells. In piglets given hydrocortisone before explantation, the number of virus-producing explants was not enhanced as compared to that of virus-producing explants from untreated animals.", "contents": "Latent pseudorabies virus infection in pigs. Latent infection with the TOP strain of pseudorabies virus (PRV) was established in 6 weeks old piglets. Infectious virus was found in oropharyngeal swabs till day 10 post infection (p.i.); later on, attempts to detect the virus remained unsuccessful. However, PRV could be isolated by explantation of tonsils, cervical lymph nodes, nasal mucosa and gasserian ganglia. These tissues were removed between 160 and 181 days p.i., during cultivation, infectious PRV was released into the culture fluid from the 3rd to the 11th day of the explantation. PRV antigen was seen by immunofluorescence only in explants coming from gasserian ganglia. It was localized in both neurons and satellite cells. In piglets given hydrocortisone before explantation, the number of virus-producing explants was not enhanced as compared to that of virus-producing explants from untreated animals."}
{"id": "PMID:9802", "title": "Experimental live tick-borne encephalitis vaccine (Labgat E5 \"14\" virus clone): volunteers 1 and 2 years after single-dose immunization.", "content": "Groups of volunteers given intramuscularly 5 or 6.5 dex or perorally 6.5 dex newborn mouse icLD50 of the plaquesegregated \"14\" clone of the Langat E5 virus strain (tick-borne encephalitis comples) were followed for periods of 12 and 24-27 months. Circulating specific virus neutralizing antibodies persisted in them in the absence of apparent reaction as evidenced by clinical, electroencephalographic and cerebrospinal fluid findings.", "contents": "Experimental live tick-borne encephalitis vaccine (Labgat E5 \"14\" virus clone): volunteers 1 and 2 years after single-dose immunization. Groups of volunteers given intramuscularly 5 or 6.5 dex or perorally 6.5 dex newborn mouse icLD50 of the plaquesegregated \"14\" clone of the Langat E5 virus strain (tick-borne encephalitis comples) were followed for periods of 12 and 24-27 months. Circulating specific virus neutralizing antibodies persisted in them in the absence of apparent reaction as evidenced by clinical, electroencephalographic and cerebrospinal fluid findings."}
{"id": "PMID:9803", "title": "Experimental infection of Macaca mulatta monkeys with Lednice (Yaba 1) virus.", "content": "Macaca mulatta monkeys were inoculated with Lednice (Yaba 1) virus strain 6118. The animals developed no clinical signs and the body temperature and values of complete haematological examination remained within normal limits. In spite of positive immunofluorescence in regional lymph nodes, no virus could be recovered from them by passages in mice. Viraemia was not demonstrated. The antibody response was directly proportional to the amount of virus inoculated, i.e. it was significant after a higher virus dose or after repeated inoculation. The results obtained are discussed in respect of and in comparison with serological findings in man.", "contents": "Experimental infection of Macaca mulatta monkeys with Lednice (Yaba 1) virus. Macaca mulatta monkeys were inoculated with Lednice (Yaba 1) virus strain 6118. The animals developed no clinical signs and the body temperature and values of complete haematological examination remained within normal limits. In spite of positive immunofluorescence in regional lymph nodes, no virus could be recovered from them by passages in mice. Viraemia was not demonstrated. The antibody response was directly proportional to the amount of virus inoculated, i.e. it was significant after a higher virus dose or after repeated inoculation. The results obtained are discussed in respect of and in comparison with serological findings in man."}
{"id": "PMID:9804", "title": "A stable antibody-sensitized erythrocyte diagnostic preparation for detection of rhinovirus type 17 and its antibody.", "content": "A diagnostic preparation was obtained by sensitization of formalinized sheep erythrocytes with antibody to rhinovirus type 17. This preparation was agglutinated in the presence of relatively high concentrations of type 17 but not other types of rhinovirus. It could also be used for detection of antibody to rhinovirus type 17 in the antigen neutralization test, the antibody levels determined in this way being similar to those found by conventional virus neutralization tests in cell cultures.", "contents": "A stable antibody-sensitized erythrocyte diagnostic preparation for detection of rhinovirus type 17 and its antibody. A diagnostic preparation was obtained by sensitization of formalinized sheep erythrocytes with antibody to rhinovirus type 17. This preparation was agglutinated in the presence of relatively high concentrations of type 17 but not other types of rhinovirus. It could also be used for detection of antibody to rhinovirus type 17 in the antigen neutralization test, the antibody levels determined in this way being similar to those found by conventional virus neutralization tests in cell cultures."}
{"id": "PMID:9805", "title": "Soldado virus from Ornithodoros (Alectorobius) maritimus (Ixodoidea: Argasidae) infesting herring gull nests on Puffin Island, Northern Wales.", "content": "Three strains of Soldado (SOL) virus (Hughes serogroup) were isolated from nymphal and adult Ornithodoros (Alectorobius) maritimus Vermeil et Marguet collected in and near nests of the Herring Gull, Larus a. argentatus Pontoppidan, on Puffin Island, northern Wales. Reciprocal complement fixation (CF) titration results demonstrated recovered virus strains to be SOL virus and antigenically distinct from other Hughes serogroup members. All isolates killed mice and guinea pigs, and 1-2 day old domestic chicks when inoculated intracerebrally.", "contents": "Soldado virus from Ornithodoros (Alectorobius) maritimus (Ixodoidea: Argasidae) infesting herring gull nests on Puffin Island, Northern Wales. Three strains of Soldado (SOL) virus (Hughes serogroup) were isolated from nymphal and adult Ornithodoros (Alectorobius) maritimus Vermeil et Marguet collected in and near nests of the Herring Gull, Larus a. argentatus Pontoppidan, on Puffin Island, northern Wales. Reciprocal complement fixation (CF) titration results demonstrated recovered virus strains to be SOL virus and antigenically distinct from other Hughes serogroup members. All isolates killed mice and guinea pigs, and 1-2 day old domestic chicks when inoculated intracerebrally."}
{"id": "PMID:9806", "title": "Infection of Hela cells with a virulent and an attenuated strain of pseudorabies virus studied by electron microscopy.", "content": "Hollow-core particles, forming crystals in nuclei, prevailed in HeLa cells infected with an attenuated strain of pseudorabies virus (PRV). After infection with a virulent PRV strain, the cells contained mainly fully infectious dense-core particles. These findings might explain the lower susceptibility of HeLa and some other human cells to infection with attenuated strains of PRV as compared to virulent strains.", "contents": "Infection of Hela cells with a virulent and an attenuated strain of pseudorabies virus studied by electron microscopy. Hollow-core particles, forming crystals in nuclei, prevailed in HeLa cells infected with an attenuated strain of pseudorabies virus (PRV). After infection with a virulent PRV strain, the cells contained mainly fully infectious dense-core particles. These findings might explain the lower susceptibility of HeLa and some other human cells to infection with attenuated strains of PRV as compared to virulent strains."}
{"id": "PMID:9807", "title": "Respiratory syncytial virus-specific RNA synthesis in primary monkey kidney cell cultures.", "content": "Primary rhesus monkey kidney (MK) cell cultures were inoculated with respiratory syncytial virus and treated or untreated with actinomycin D before pulse labeling with uridine-5-3H. The virus-specific RNA synthesis was noted at its peak in the nucleoplasm and possibly less so in the cytoplasm of infected cells. At 48 and 72 hours post-inoculation (p.i.), small fractions of available cells were synthesising virus-specific RNA with labeling index of 15% and 18% respectively. By 48 hours p.i. syncytia started appearing and a higher grain count in the cytoplasm of actinomycin D-treated infected cells was noted.", "contents": "Respiratory syncytial virus-specific RNA synthesis in primary monkey kidney cell cultures. Primary rhesus monkey kidney (MK) cell cultures were inoculated with respiratory syncytial virus and treated or untreated with actinomycin D before pulse labeling with uridine-5-3H. The virus-specific RNA synthesis was noted at its peak in the nucleoplasm and possibly less so in the cytoplasm of infected cells. At 48 and 72 hours post-inoculation (p.i.), small fractions of available cells were synthesising virus-specific RNA with labeling index of 15% and 18% respectively. By 48 hours p.i. syncytia started appearing and a higher grain count in the cytoplasm of actinomycin D-treated infected cells was noted."}
{"id": "PMID:9808", "title": "Cultivation of foot and mouth disease virus in bovine leukocyte cultures for use in the complement fixation test.", "content": "Bovine leukocyte cultures achieved good growth after 72 hours of cultivation. Foot-and mouth disease (FMD) virus type 0 multiplied in such cultures to a titre of 10(6) TCID50/0.1 ml. The cell culture-grown virus was found to be suitable for the complement fixation test (CFT) after purification and concentration with calcium phosphate.", "contents": "Cultivation of foot and mouth disease virus in bovine leukocyte cultures for use in the complement fixation test. Bovine leukocyte cultures achieved good growth after 72 hours of cultivation. Foot-and mouth disease (FMD) virus type 0 multiplied in such cultures to a titre of 10(6) TCID50/0.1 ml. The cell culture-grown virus was found to be suitable for the complement fixation test (CFT) after purification and concentration with calcium phosphate."}
{"id": "PMID:9809", "title": "Non-infectious tick-borne encephalitis antigen.", "content": "After formalin treatment of sucrose-acetone antigens, prepared from different tick-borne encephalitis (TBE) virus strains, their haemagglutination (HA) activity was preserved or even higher than that of untreated antigens. Formalin-treated TBE antigen was non-infectious and thus may be recommended for routine work to avoid laboratory infections.", "contents": "Non-infectious tick-borne encephalitis antigen. After formalin treatment of sucrose-acetone antigens, prepared from different tick-borne encephalitis (TBE) virus strains, their haemagglutination (HA) activity was preserved or even higher than that of untreated antigens. Formalin-treated TBE antigen was non-infectious and thus may be recommended for routine work to avoid laboratory infections."}
{"id": "PMID:9816", "title": "Molecular weight analysis of the polypeptides of cholera phage PL 163/10 by polyacrylamide gel electrophoresis.", "content": "Cholera phage PL 163/10, belonging to Mukerjee's Group I, was purified by alternate cycles of low and high speed centrifugation. Gel electrophoresis revealed the presence of four polypeptide chains of respective molecular weights of 10,370+/-515 (A), 30,000+/-1,303 (B), 40,000+/-1,049(C) and 64,000+/-2,433 (D) daltons. Electrophoresis of the sample alkylated with iodoacetic acid resolved the presence of only one polypeptide chain of an average molecular weight of 10,310+/-565 daltons. The polypeptides B, C and D could be interpreted as trimer, tetramer and hexamer respectively of the polypeptide A, which was the basic structural protein of this phage.", "contents": "Molecular weight analysis of the polypeptides of cholera phage PL 163/10 by polyacrylamide gel electrophoresis. Cholera phage PL 163/10, belonging to Mukerjee's Group I, was purified by alternate cycles of low and high speed centrifugation. Gel electrophoresis revealed the presence of four polypeptide chains of respective molecular weights of 10,370+/-515 (A), 30,000+/-1,303 (B), 40,000+/-1,049(C) and 64,000+/-2,433 (D) daltons. Electrophoresis of the sample alkylated with iodoacetic acid resolved the presence of only one polypeptide chain of an average molecular weight of 10,310+/-565 daltons. The polypeptides B, C and D could be interpreted as trimer, tetramer and hexamer respectively of the polypeptide A, which was the basic structural protein of this phage."}
{"id": "PMID:9817", "title": "Investigation on the biological activity of fowl plague virus ribonucleoprotein.", "content": "Fowl plague virus (FPV) ribonucleoprotein (RNP) bands in sucrose density gradient in a heterogeneous peak with sedimentation coefficients from 45 to 70 S, whereas in cesium chloride gradient it has a homogeneous density of 1.33-1.34 g/cm3. FPV RNP contains 7.4-8% RNA. Upon inoculation of chick embryo cell cultures. FPV RNP shows no infectivity, does not induce virus-specific protein synthesis and does not participate in complementation or recombination interactions with ts mutants of FPV. The biological activity of FPV RNP demonstrable under certain experimental conditions is due to admixture of undestroyed virions and is completely eliminated by treatment of the preparation with gamma-globulin fraction of antiserum to FPV haemagglutinin, but not with antiserum to RNP proteins.", "contents": "Investigation on the biological activity of fowl plague virus ribonucleoprotein. Fowl plague virus (FPV) ribonucleoprotein (RNP) bands in sucrose density gradient in a heterogeneous peak with sedimentation coefficients from 45 to 70 S, whereas in cesium chloride gradient it has a homogeneous density of 1.33-1.34 g/cm3. FPV RNP contains 7.4-8% RNA. Upon inoculation of chick embryo cell cultures. FPV RNP shows no infectivity, does not induce virus-specific protein synthesis and does not participate in complementation or recombination interactions with ts mutants of FPV. The biological activity of FPV RNP demonstrable under certain experimental conditions is due to admixture of undestroyed virions and is completely eliminated by treatment of the preparation with gamma-globulin fraction of antiserum to FPV haemagglutinin, but not with antiserum to RNP proteins."}
{"id": "PMID:9818", "title": "Interaction of plasma membranes with influenza virus. VI. The possible role of the adenylate cyclase system.", "content": "The amounts of released soluble (s) antigen of influenza A/WSN virus were increased when the virus was allowed to interact with isolated plasma membranes in a medium containing substances enhancing the level of adenosine 3',5' cyclic monophosphate (c'AMP) or activating the enzyme adenylate cyclase. By contrast, less s-antigen was released upon addition to the incubation medium of foetal calf serum or calf serum proteins which activate c'AMP phosphodiesterase and thus decrease the level of c'AMP. Changes in the amount of released s-antigen were parallelled by changes in the activities of membrane Ca-adenosine triphosphatase and creatine phosphokinase.", "contents": "Interaction of plasma membranes with influenza virus. VI. The possible role of the adenylate cyclase system. The amounts of released soluble (s) antigen of influenza A/WSN virus were increased when the virus was allowed to interact with isolated plasma membranes in a medium containing substances enhancing the level of adenosine 3',5' cyclic monophosphate (c'AMP) or activating the enzyme adenylate cyclase. By contrast, less s-antigen was released upon addition to the incubation medium of foetal calf serum or calf serum proteins which activate c'AMP phosphodiesterase and thus decrease the level of c'AMP. Changes in the amount of released s-antigen were parallelled by changes in the activities of membrane Ca-adenosine triphosphatase and creatine phosphokinase."}
{"id": "PMID:9819", "title": "Virion heat-sensitivity of adenovirus type 5 temperature-sensitive mutants and interferon induction.", "content": "Kinetics of interferon induction with wild type adenovirus 5, and three temperature-sensitive mutants, ts 1, ts 18 and ts 19 were examined in chick embryo cells (CEC) at permissive (31 degrees C) and non-permissive (38 degrees C) temperatures. Interferon levels reached a maximum four days after infection with the wild type and all ts mutants at 31 degrees C. However, at 38 degrees C, ts 18 and ts 19 failed to induce interferon, while wild type and ts 1 induced normal levels which reached a maximum by three days after infection. Striking differences in virion heat sensitivities between wild type, ts 1, ts 18 and ts 19 at both 50 degrees C and 52 degrees C were detected. These results suggested that ts 18 and ts 19 might each have a mutation in a gene coding for a virion structural component. The production of infectious progeny by shift-up experiments on Hela cells showed that mutant ts 18 was affected immediately after shift-up at all times throughout the growth cycle. On the other hand, interferon production in CEC by mutant ts 18 was only affected by shift-up during the first five hours of incubation, which indicated involvement of an early gene function in elliciting interferon production.", "contents": "Virion heat-sensitivity of adenovirus type 5 temperature-sensitive mutants and interferon induction. Kinetics of interferon induction with wild type adenovirus 5, and three temperature-sensitive mutants, ts 1, ts 18 and ts 19 were examined in chick embryo cells (CEC) at permissive (31 degrees C) and non-permissive (38 degrees C) temperatures. Interferon levels reached a maximum four days after infection with the wild type and all ts mutants at 31 degrees C. However, at 38 degrees C, ts 18 and ts 19 failed to induce interferon, while wild type and ts 1 induced normal levels which reached a maximum by three days after infection. Striking differences in virion heat sensitivities between wild type, ts 1, ts 18 and ts 19 at both 50 degrees C and 52 degrees C were detected. These results suggested that ts 18 and ts 19 might each have a mutation in a gene coding for a virion structural component. The production of infectious progeny by shift-up experiments on Hela cells showed that mutant ts 18 was affected immediately after shift-up at all times throughout the growth cycle. On the other hand, interferon production in CEC by mutant ts 18 was only affected by shift-up during the first five hours of incubation, which indicated involvement of an early gene function in elliciting interferon production."}
{"id": "PMID:9820", "title": "Ts mutant of NWS influenza virus: behaviour in vitro and in vivo.", "content": "After passaging the NWS influenza virus at increasing temperatures in the hamster embryo fibroblast (HEF) cell line, a temperature-resistant (tr) mutant which grew well at 39 degrees C was isolated. Attempts were made to isolate temperature-sensitive (ts) mutants from the tr virus. After growth in the presence of 5-fluorouracil, 233 virus clones were isolated. Among these only one was incapable of replicating at 39 degrees C. The physiological studies, the shift-up experiment and the electron microscopic investigation suggested that the genetic defect responsible for its ts character influenced a late function of the virus genome. In the lungs of intranasally infected mice, the ts mutant replicated to a lesser extent than the tr virus. During its growth in vivo, the ts virus exhibited a high degree of genetic stability.", "contents": "Ts mutant of NWS influenza virus: behaviour in vitro and in vivo. After passaging the NWS influenza virus at increasing temperatures in the hamster embryo fibroblast (HEF) cell line, a temperature-resistant (tr) mutant which grew well at 39 degrees C was isolated. Attempts were made to isolate temperature-sensitive (ts) mutants from the tr virus. After growth in the presence of 5-fluorouracil, 233 virus clones were isolated. Among these only one was incapable of replicating at 39 degrees C. The physiological studies, the shift-up experiment and the electron microscopic investigation suggested that the genetic defect responsible for its ts character influenced a late function of the virus genome. In the lungs of intranasally infected mice, the ts mutant replicated to a lesser extent than the tr virus. During its growth in vivo, the ts virus exhibited a high degree of genetic stability."}
{"id": "PMID:9821", "title": "Replication dynamics of tick-borne encephalitis virus in, and glycolytic activity of, human diploid cells.", "content": "Tick-borne encephalitis (TBE) virus (Western subtype) strains replicated very rapidly in human diploid embryonic lung (HDEL) cells, namely within the first 24 hours of infection. Greater amounts of both intra- and extracellular virus were produced after inoculation of a virulent than of an attenuated strain. With the virulent strain, more infectious virus was found in the medium than in the cells: the opposite was true for the attenuated strain. No cytopathic effect was observed during the period studied. The rates of glucose uptake and lactate production by cells were markedly influenced by the infection. Lactate production was retarded by both virus strains to a comparable degree. Glucose uptake was markedly increased, appreciably more so after infection by the virulent than the attenuated strain. A method for differentiating between attenuated and virulent strains based on the determination of glucose conthe medium was developed.", "contents": "Replication dynamics of tick-borne encephalitis virus in, and glycolytic activity of, human diploid cells. Tick-borne encephalitis (TBE) virus (Western subtype) strains replicated very rapidly in human diploid embryonic lung (HDEL) cells, namely within the first 24 hours of infection. Greater amounts of both intra- and extracellular virus were produced after inoculation of a virulent than of an attenuated strain. With the virulent strain, more infectious virus was found in the medium than in the cells: the opposite was true for the attenuated strain. No cytopathic effect was observed during the period studied. The rates of glucose uptake and lactate production by cells were markedly influenced by the infection. Lactate production was retarded by both virus strains to a comparable degree. Glucose uptake was markedly increased, appreciably more so after infection by the virulent than the attenuated strain. A method for differentiating between attenuated and virulent strains based on the determination of glucose conthe medium was developed."}
{"id": "PMID:9822", "title": "Affinity chromatography of mouse interferon: a modified purification procedure utilizing specifically purified antibodies.", "content": "Interferon preparations of a high degree of purity were obtained by a one-step procedure using affinity chromatography on specifically purified immunoadsorbent. The procedure consisted of binding interferon harvested from serum-free medium and purified by Zn-acetate precipitation and SP-Sephadex chromatography to CNBr-activated Sepharose 4B (Column No. 1). In the next step, antiinterferon globulin was purified by affinity chromatography on Column No. 1 with the bound interferon. In this way, antibodies against purified interferon, which were free from non-antibody components, were obtained. The purified antibodies were then coupled to CNBr-activated Sepharose 4B forming Column No. 2. The latter had a binding capacity of 125 800 mouse interferon units per 4.8 ml of gel. This capacity was not altered during an 8-month period of use. The gel was capable to bind interferons obtained from fibroblasts and leukocytes and, partially, from serum. The resulting purified, products were similar, i.e. they were not influenced by volume, interferon activity, or purity of the starting material. The electrophoretic profiles of the products had a similar shape irrespective of the origin of the starting material.", "contents": "Affinity chromatography of mouse interferon: a modified purification procedure utilizing specifically purified antibodies. Interferon preparations of a high degree of purity were obtained by a one-step procedure using affinity chromatography on specifically purified immunoadsorbent. The procedure consisted of binding interferon harvested from serum-free medium and purified by Zn-acetate precipitation and SP-Sephadex chromatography to CNBr-activated Sepharose 4B (Column No. 1). In the next step, antiinterferon globulin was purified by affinity chromatography on Column No. 1 with the bound interferon. In this way, antibodies against purified interferon, which were free from non-antibody components, were obtained. The purified antibodies were then coupled to CNBr-activated Sepharose 4B forming Column No. 2. The latter had a binding capacity of 125 800 mouse interferon units per 4.8 ml of gel. This capacity was not altered during an 8-month period of use. The gel was capable to bind interferons obtained from fibroblasts and leukocytes and, partially, from serum. The resulting purified, products were similar, i.e. they were not influenced by volume, interferon activity, or purity of the starting material. The electrophoretic profiles of the products had a similar shape irrespective of the origin of the starting material."}
{"id": "PMID:9823", "title": "Use of cross-linking in studying the structure of RNA tumour viruses.", "content": "Treatment of intact avian myeloblastosis virus (AMV) with dimethyl suberimidate dihydrochloride (DMS), a cross-linking agent specific for amino groups, was found to result in progressive cross-linking among viral proteins, as revealed by polyacrylamide gel electrophoresis (PAGE) in the presence of sodium dodecyl sulphate (SDS). Free viral proteins were not cross-linked. The cross-linked protein complex with an apparent molecular weight of 50,000 daltons was studied in detail.", "contents": "Use of cross-linking in studying the structure of RNA tumour viruses. Treatment of intact avian myeloblastosis virus (AMV) with dimethyl suberimidate dihydrochloride (DMS), a cross-linking agent specific for amino groups, was found to result in progressive cross-linking among viral proteins, as revealed by polyacrylamide gel electrophoresis (PAGE) in the presence of sodium dodecyl sulphate (SDS). Free viral proteins were not cross-linked. The cross-linked protein complex with an apparent molecular weight of 50,000 daltons was studied in detail."}
{"id": "PMID:9824", "title": "Eyach--an arthropod-borne virus related to Colorado tick fever virus in the Federal Republic of Germany.", "content": "From Ixodes ricinus ticks collected in a tick-borne encephalitis focus in Baden-W\u00fcrttemberg, an agent pathogenic exclusively for suckling mice was isolated. Obviously a virus, it passed membrane filters with a pore width of 200 nm. It was resistant to ether and sodium deoxycholate, but not to chloroform. In the complement fixation test it showed a close, and in the neutralisation test a more one-sided relationship to Colorado tick fever virus.", "contents": "Eyach--an arthropod-borne virus related to Colorado tick fever virus in the Federal Republic of Germany. From Ixodes ricinus ticks collected in a tick-borne encephalitis focus in Baden-W\u00fcrttemberg, an agent pathogenic exclusively for suckling mice was isolated. Obviously a virus, it passed membrane filters with a pore width of 200 nm. It was resistant to ether and sodium deoxycholate, but not to chloroform. In the complement fixation test it showed a close, and in the neutralisation test a more one-sided relationship to Colorado tick fever virus."}
{"id": "PMID:9825", "title": "Effect of adamantane derivatives on the activity of orthomyxovirus RNA-dependent RNA polymerase.", "content": "The effect of several adamantane derivatives on the activity of virion-associated RNA-dependent RNA polymerase of fowl plague virus (FPV) and influenza B virus was studied in vitro. Some of the derivatives inhibited the activity of the polymerase by 60 per cent. A correlation was established between the previously demonstrated capacity of these inhibitors to suppress orthomyxovirus reproduction in vivo and their ability to reduce the activity of virion-associated RNA-dependent RNA polymerase in vitro.", "contents": "Effect of adamantane derivatives on the activity of orthomyxovirus RNA-dependent RNA polymerase. The effect of several adamantane derivatives on the activity of virion-associated RNA-dependent RNA polymerase of fowl plague virus (FPV) and influenza B virus was studied in vitro. Some of the derivatives inhibited the activity of the polymerase by 60 per cent. A correlation was established between the previously demonstrated capacity of these inhibitors to suppress orthomyxovirus reproduction in vivo and their ability to reduce the activity of virion-associated RNA-dependent RNA polymerase in vitro."}
{"id": "PMID:9826", "title": "Increased resistance of an interferon-resistant cell subline to the toxic effect of double-stranded RNA.", "content": "The toxicity of double-stranded (ds) f2-phage RNA for interferon-treated L cells and an interferon-resistant subline of L cells (CVS cells) was compared. The interferon-resistant subline proved to be about 20 times more resistant to ds RNA than the parent L cells. The degree of toxicity of ds RNA was dependent on the concentration of interferon to which the cells were exposed.", "contents": "Increased resistance of an interferon-resistant cell subline to the toxic effect of double-stranded RNA. The toxicity of double-stranded (ds) f2-phage RNA for interferon-treated L cells and an interferon-resistant subline of L cells (CVS cells) was compared. The interferon-resistant subline proved to be about 20 times more resistant to ds RNA than the parent L cells. The degree of toxicity of ds RNA was dependent on the concentration of interferon to which the cells were exposed."}
{"id": "PMID:9827", "title": "[Some aspects of phylogenetic development of cellular immune reaction in vertebrates].", "content": "The division of the immune system into humoral and cell-mediated immunity is established in vertebrates. Moreover single manifestations of cell-mediated immunity are observed in invertebrates, too. In protochordates, e.g., a genetically fixed ability to recognize \"Self\" and \"Not-Self\" could already be demonstrated, but the interpretation of this phenomenon as a preliminary stage of cell-mediated immunity in vertebrates is not established yet. Especially by the investigation of the transplantation tolerance, for example between mammalia and inferior vertebrates, essential results as to the development of the immune system in vertebrates could be obtained. It is quite sure that the experimental findings obtained till now are not sufficient for giming a complete picture of the phylogenesis of immunologic reactivity. But they very unanimously support the conception that nearly all of the nowadays living representatives of the vertebrates dispose of cell-mediated immunity, which is equal in its characteristic features. And the small lymphocyte takes the central part in the cell-mediated immune reactions of the vertebrates, and the complexity of the lymphoid organs, which is increasing in the course of phylogenesis leads to a quantitative but not to a qualitative change.", "contents": "[Some aspects of phylogenetic development of cellular immune reaction in vertebrates]. The division of the immune system into humoral and cell-mediated immunity is established in vertebrates. Moreover single manifestations of cell-mediated immunity are observed in invertebrates, too. In protochordates, e.g., a genetically fixed ability to recognize \"Self\" and \"Not-Self\" could already be demonstrated, but the interpretation of this phenomenon as a preliminary stage of cell-mediated immunity in vertebrates is not established yet. Especially by the investigation of the transplantation tolerance, for example between mammalia and inferior vertebrates, essential results as to the development of the immune system in vertebrates could be obtained. It is quite sure that the experimental findings obtained till now are not sufficient for giming a complete picture of the phylogenesis of immunologic reactivity. But they very unanimously support the conception that nearly all of the nowadays living representatives of the vertebrates dispose of cell-mediated immunity, which is equal in its characteristic features. And the small lymphocyte takes the central part in the cell-mediated immune reactions of the vertebrates, and the complexity of the lymphoid organs, which is increasing in the course of phylogenesis leads to a quantitative but not to a qualitative change."}
{"id": "PMID:9828", "title": "Evaluation of serum ionic calcium measurement in a general hospital population.", "content": "Direct measurement of ionic calcium was evaluated in light of conflicting reports concerning the correlation of ionic calcium with total calcium and ionic calcium as predicted from total calcium and serum protein. Ionic calcium in the sera of normo- hypo-, and hypercalcemic adult hospitalized patients was measured anaerobically using an Orion model 98-20 calcium flow-thorugh electrode. Good correlation (r = .77) was found with the calculated ionic calcium value derived from total protein and total calcium, using the McLean-Hastings nomogram. Good correlation was also present between the measured ionic and total calcium (r = .80). In view of these correlations, the introduction of serum ionic calcium measurements into the general hospital laboratory repertoire is of questionable value.", "contents": "Evaluation of serum ionic calcium measurement in a general hospital population. Direct measurement of ionic calcium was evaluated in light of conflicting reports concerning the correlation of ionic calcium with total calcium and ionic calcium as predicted from total calcium and serum protein. Ionic calcium in the sera of normo- hypo-, and hypercalcemic adult hospitalized patients was measured anaerobically using an Orion model 98-20 calcium flow-thorugh electrode. Good correlation (r = .77) was found with the calculated ionic calcium value derived from total protein and total calcium, using the McLean-Hastings nomogram. Good correlation was also present between the measured ionic and total calcium (r = .80). In view of these correlations, the introduction of serum ionic calcium measurements into the general hospital laboratory repertoire is of questionable value."}
{"id": "PMID:9829", "title": "Stability of several brands of ampicillin and penicillin V potassium oral liquids following reconstitution.", "content": "The stability-time profiles of the active ingredient of five generically equivalent brands of penicillin V potassium for oral solution, and of five generically equivalent brands of ampicillin for oral suspension, were studied. Three controlled conditions were employed-refrigerated, room and elevated temperature-and all the samples were assayed chemically for drug remaining at specific time intervals after reconstitution. The results showed that considerable variations in the initial concentrations of active component existed among the various ampicillin and penicillin products. In one penicillin product the official content requirement was not met. The data also showed that although the labels on each of the commerical penicillin products tested indicate that the reconstituted products may be stored in a refrigerator for 14 days without significant loss of potency, only one penicillin product still met 90% of label claim (minimal potency requirement of the United States Pharmacopeia for dry powder). All ampicillin products tested were stable when stored at the conditions recommended by the manufacturers, but the trihydrate forms exhibited greater stability than the anhydrous forms, probably because of the more rapid dissolution rate of anhydrous ampicillin.", "contents": "Stability of several brands of ampicillin and penicillin V potassium oral liquids following reconstitution. The stability-time profiles of the active ingredient of five generically equivalent brands of penicillin V potassium for oral solution, and of five generically equivalent brands of ampicillin for oral suspension, were studied. Three controlled conditions were employed-refrigerated, room and elevated temperature-and all the samples were assayed chemically for drug remaining at specific time intervals after reconstitution. The results showed that considerable variations in the initial concentrations of active component existed among the various ampicillin and penicillin products. In one penicillin product the official content requirement was not met. The data also showed that although the labels on each of the commerical penicillin products tested indicate that the reconstituted products may be stored in a refrigerator for 14 days without significant loss of potency, only one penicillin product still met 90% of label claim (minimal potency requirement of the United States Pharmacopeia for dry powder). All ampicillin products tested were stable when stored at the conditions recommended by the manufacturers, but the trihydrate forms exhibited greater stability than the anhydrous forms, probably because of the more rapid dissolution rate of anhydrous ampicillin."}
{"id": "PMID:9832", "title": "Comparison of microelectrode, DMO, and methylamine methods for measuring intracellular pH.", "content": "The intracellular pH (pHi) of giant barnacle muscle fibers was measured with glass microelectrodes and also calculated from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) and methylamine (MA). Simultaneously applying any two of these methods to muscle fibers of the same barnacle, we found the pH measured with an intracellular electrode (pH-Elec) to be about 0.06 higher than the DMO-derived pH (pH-DMO), and pH-DMO to be about 0.10 higher than the MA-derived pH (p-ma). in studies on the pHi of squid giant axons, we found that pH-Elec (7.35) and pH-DMO (7.36) were not significantly different. In the barnacle experiments, DMO required about 30 min to reach a steady-state distribution, while MA required more than 5 h. The deviations of pH-DMO and pH-MA from pH-Elec for the barnacle can be explained by a) an error in the assumed intracellular pKa' of DMO or MA, b) membrane permeability to the ionic form of DMO or MA, or c) intracellular compartmentalization. Included is a detailed study of the apparent dissociation constant of DMO as affected by temperature, and ionic strength and composition.", "contents": "Comparison of microelectrode, DMO, and methylamine methods for measuring intracellular pH. The intracellular pH (pHi) of giant barnacle muscle fibers was measured with glass microelectrodes and also calculated from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) and methylamine (MA). Simultaneously applying any two of these methods to muscle fibers of the same barnacle, we found the pH measured with an intracellular electrode (pH-Elec) to be about 0.06 higher than the DMO-derived pH (pH-DMO), and pH-DMO to be about 0.10 higher than the MA-derived pH (p-ma). in studies on the pHi of squid giant axons, we found that pH-Elec (7.35) and pH-DMO (7.36) were not significantly different. In the barnacle experiments, DMO required about 30 min to reach a steady-state distribution, while MA required more than 5 h. The deviations of pH-DMO and pH-MA from pH-Elec for the barnacle can be explained by a) an error in the assumed intracellular pKa' of DMO or MA, b) membrane permeability to the ionic form of DMO or MA, or c) intracellular compartmentalization. Included is a detailed study of the apparent dissociation constant of DMO as affected by temperature, and ionic strength and composition."}
{"id": "PMID:9833", "title": "Cardiovascular and metabolic responses during burn shock in the guinea pig.", "content": "The hemodynamic and metabolic responses of fatally burned, nonfatally burned, and unburned control guinea pigs were compared. The burns were induced in temporarily anesthetized animals by immersion to either the xyphoid process (70% fatal) or the midabdomen (100%survival) in boiling water for 3 s. Although cardiac output was reduced in all animals postburn, the survivors (MAG) has higher cardiac outputs at lower arterial pressures than the nonsurvivors (XPN). The postburn lactate levels in the XPN were higher than in the MAG, and the postburn values for pH, oxygen consumption, and core temperature were lower in the XPN. In each group, hyperglycemia was evident for 8 h postburn and terminal plasma glucose concentrations were usually elevated or similar to the prevalue. It was concluded that fatal and nonfatal burn shock were distinguished primarily by differences in tissue perfusion.", "contents": "Cardiovascular and metabolic responses during burn shock in the guinea pig. The hemodynamic and metabolic responses of fatally burned, nonfatally burned, and unburned control guinea pigs were compared. The burns were induced in temporarily anesthetized animals by immersion to either the xyphoid process (70% fatal) or the midabdomen (100%survival) in boiling water for 3 s. Although cardiac output was reduced in all animals postburn, the survivors (MAG) has higher cardiac outputs at lower arterial pressures than the nonsurvivors (XPN). The postburn lactate levels in the XPN were higher than in the MAG, and the postburn values for pH, oxygen consumption, and core temperature were lower in the XPN. In each group, hyperglycemia was evident for 8 h postburn and terminal plasma glucose concentrations were usually elevated or similar to the prevalue. It was concluded that fatal and nonfatal burn shock were distinguished primarily by differences in tissue perfusion."}
{"id": "PMID:9834", "title": "Autoregulation of cerebral blood flow and its relation to cerebrospinal fluid pH.", "content": "Internal carotid artery blood flow (IFBF) was determined in each of nine Macaca mulatta by means of a flow transducer implanted around an internal carotid artery. The monkeys were lightly anesthetized, intubated, and paralyzed. Normoxia and normocarbia were maintained stable throughout the experiment. ICBF was monitored while mean arterial blood pressure (MABP) was lowered by withdrawal of blood. MABP was kept within the known limits of autoregulation in order not to compromise CBF. Cerebrospinal fluid (CSF) from the cisterna magna was analyzed for pH PCO2, and PO2 before and after a 30-min hypotensive period in which MABP was lowered from 116 +/- 4 to 70 +/- 2 mmHg (mean +/- SE). Corresponding HCO3- concentrations were calculated. The decrease in MABP did not result in a significant reduction in ICBF but elicited a 37% reduction in calculated cerebrovascular resistance, indicating normal autoregulation. Mena CSF pH was not significantly decreased (P less than 0.05); it changed from 7.320 +/- 0.010 to 7.317 +/- 0.010 after the induced hypotensive period. Thus CSF pH does not appear to have a significant role in cerebral blood flow autoregulation.", "contents": "Autoregulation of cerebral blood flow and its relation to cerebrospinal fluid pH. Internal carotid artery blood flow (IFBF) was determined in each of nine Macaca mulatta by means of a flow transducer implanted around an internal carotid artery. The monkeys were lightly anesthetized, intubated, and paralyzed. Normoxia and normocarbia were maintained stable throughout the experiment. ICBF was monitored while mean arterial blood pressure (MABP) was lowered by withdrawal of blood. MABP was kept within the known limits of autoregulation in order not to compromise CBF. Cerebrospinal fluid (CSF) from the cisterna magna was analyzed for pH PCO2, and PO2 before and after a 30-min hypotensive period in which MABP was lowered from 116 +/- 4 to 70 +/- 2 mmHg (mean +/- SE). Corresponding HCO3- concentrations were calculated. The decrease in MABP did not result in a significant reduction in ICBF but elicited a 37% reduction in calculated cerebrovascular resistance, indicating normal autoregulation. Mena CSF pH was not significantly decreased (P less than 0.05); it changed from 7.320 +/- 0.010 to 7.317 +/- 0.010 after the induced hypotensive period. Thus CSF pH does not appear to have a significant role in cerebral blood flow autoregulation."}
{"id": "PMID:9835", "title": "Characteristics of phosphate transport in isolated proximal tubule.", "content": "The characteristics of inorganic phosphate transport in isolated perfused proximal tubules of the rabbit were examined using radioisotopic techniques. When tubules were perfused with an ultrafiltrate of rabbit serum, the mean lumen-to-bath flux of phosphate in the convoluted segment was 6.60 +/- 1.41 (SE) pmol/mm-min with a simultaneous back-to-lumen flux of 0.45 +/- 0.08. In the straight portion of the proximal tubule, the lumen-to-bath flux was significantly lower (P less than 0.01) at 2.22 +/- 0.48 pmol/min-min with a bath-to-lumen flux of 0.31 +/- 0.05. The lumen-to-bath flux was not affected by increases in the intraluminal phosphate concentration from 2.00 +/- 0.19 to 3.12 +/- 0.34 mM or by the isohydric replacement of bicarbonate in the ambient fluids with chloride. However, phosphate absorption was completely inhibited by ouabain 10(-5) M in the bath. These data indicate that phosphate absorption in these segments occurs by a mechanism other than independent diffusion and is saturated at phosphate concentrations characteristic of normal glomerular filtrate. There is no evidence for significant phosphate transport from bath to lumen.", "contents": "Characteristics of phosphate transport in isolated proximal tubule. The characteristics of inorganic phosphate transport in isolated perfused proximal tubules of the rabbit were examined using radioisotopic techniques. When tubules were perfused with an ultrafiltrate of rabbit serum, the mean lumen-to-bath flux of phosphate in the convoluted segment was 6.60 +/- 1.41 (SE) pmol/mm-min with a simultaneous back-to-lumen flux of 0.45 +/- 0.08. In the straight portion of the proximal tubule, the lumen-to-bath flux was significantly lower (P less than 0.01) at 2.22 +/- 0.48 pmol/min-min with a bath-to-lumen flux of 0.31 +/- 0.05. The lumen-to-bath flux was not affected by increases in the intraluminal phosphate concentration from 2.00 +/- 0.19 to 3.12 +/- 0.34 mM or by the isohydric replacement of bicarbonate in the ambient fluids with chloride. However, phosphate absorption was completely inhibited by ouabain 10(-5) M in the bath. These data indicate that phosphate absorption in these segments occurs by a mechanism other than independent diffusion and is saturated at phosphate concentrations characteristic of normal glomerular filtrate. There is no evidence for significant phosphate transport from bath to lumen."}
{"id": "PMID:9836", "title": "Atypical facial pain as a defense against psychosis.", "content": "The author describes three women who presented psychotic symptoms 24--48 hours before scheduled neurosurgical procedures for atypical facial pain; all had had extensive dental reconstruction and attempted nerve blocks with no relief. Psychiatric hospitalization and administration of major tranquilizers resulted in control of symptoms and relief of pain. Two patients were followed for a year and have had return of psychiatric symptoms or facial pain; both have been maintained on medication and have returned to normal activities. The author suggests that the facial pain may have served as a defense against the emergence of psychosis.", "contents": "Atypical facial pain as a defense against psychosis. The author describes three women who presented psychotic symptoms 24--48 hours before scheduled neurosurgical procedures for atypical facial pain; all had had extensive dental reconstruction and attempted nerve blocks with no relief. Psychiatric hospitalization and administration of major tranquilizers resulted in control of symptoms and relief of pain. Two patients were followed for a year and have had return of psychiatric symptoms or facial pain; both have been maintained on medication and have returned to normal activities. The author suggests that the facial pain may have served as a defense against the emergence of psychosis."}
{"id": "PMID:9838", "title": "The effect of lorazepam on the vasoconstriction of fear.", "content": "Volume-pulse digital plethysmography performed under ideal conditions on relatively fit adults has shown that lorazepam 4 mg intravenously abolishes the vasoconstriction of fear and restores the digital vasodilatation of the tranquil mind. The sedative effect of the drug is prolonged and is associated with several hours of anterograde amnesia from the time of its administration. The drug has no effect on the vasoconstrictor reaction to cold, pain, noise or other forms of adrenergic stimuli. Lorazepam seems to modify or prevent the psychomotor reactions which may complicate ketamine anaesthesia.", "contents": "The effect of lorazepam on the vasoconstriction of fear. Volume-pulse digital plethysmography performed under ideal conditions on relatively fit adults has shown that lorazepam 4 mg intravenously abolishes the vasoconstriction of fear and restores the digital vasodilatation of the tranquil mind. The sedative effect of the drug is prolonged and is associated with several hours of anterograde amnesia from the time of its administration. The drug has no effect on the vasoconstrictor reaction to cold, pain, noise or other forms of adrenergic stimuli. Lorazepam seems to modify or prevent the psychomotor reactions which may complicate ketamine anaesthesia."}
{"id": "PMID:9839", "title": "Anaesthesia for Caesarean section with ketamine.", "content": "Fifty healthy mothers, with normal placental function, were anaesthetised with ketamine for Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. Surgery was conducted in the lateral tilt position. Arterial blood samples were drawn from the mothers, and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. Results obtained were compared with those of a previous series anaesthetised with thiopentone, nitrous oxide, oxygen and muscle relaxants. Eight infants were clinically depressed, judged on the basis of their modified Apgar score 2 minutes after delivery. The average time to sustained respiration (TSR) was 58.1 seconds. The mean maternal pH and base excess values in the ketamine group were significantly greather than those reported after thiopentone anaesthesia. Mean Uv and Ua pH levels were also significantly higher after ketamine; in contrast, the average fetal base excess values did not differ from those obtained previously with thiopentone. The mean (Ma-Uv) and (Ma-Ua), pH gradients were 0.019 and 0.025 pH units greater respectively in the ketamine group compared to the thiopentone (P less than 0.005). The average (Uv-Ua) PO2 gradient was 3.4 mmHg less after ketamine anaesthesia (P less than 0.005). A significant inverse correlation was observed relating the I-D interval to the Ma and Ua pH values. Maternal arterial base deficit values appeared to increase with delay in delivering the fetus. Prolongation of the uterine incision to delivery (U-D) interval was associated with a decrease in Ua pH and base excess values. (Ma-Ua) pH and base excess gradients increased with lengthening of the U-D interval. No convincing evidence of awareness during anaesthesia was found during the study. Five patients, appeared to be hallucinated in the immediate post-anaesthetic period. Unpleasant dreams were reported in 5 instances. In this study ketamine appeared to be unassociated with significant biochemical asphyxia, but may have been responsible for some element of drug induced neonatal depression. In view of our own experience and that of other workers, it is suggested that ketamine induction for Caesarean section should be re-evaluated using a lower dose of the drug.", "contents": "Anaesthesia for Caesarean section with ketamine. Fifty healthy mothers, with normal placental function, were anaesthetised with ketamine for Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. Surgery was conducted in the lateral tilt position. Arterial blood samples were drawn from the mothers, and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. Results obtained were compared with those of a previous series anaesthetised with thiopentone, nitrous oxide, oxygen and muscle relaxants. Eight infants were clinically depressed, judged on the basis of their modified Apgar score 2 minutes after delivery. The average time to sustained respiration (TSR) was 58.1 seconds. The mean maternal pH and base excess values in the ketamine group were significantly greather than those reported after thiopentone anaesthesia. Mean Uv and Ua pH levels were also significantly higher after ketamine; in contrast, the average fetal base excess values did not differ from those obtained previously with thiopentone. The mean (Ma-Uv) and (Ma-Ua), pH gradients were 0.019 and 0.025 pH units greater respectively in the ketamine group compared to the thiopentone (P less than 0.005). The average (Uv-Ua) PO2 gradient was 3.4 mmHg less after ketamine anaesthesia (P less than 0.005). A significant inverse correlation was observed relating the I-D interval to the Ma and Ua pH values. Maternal arterial base deficit values appeared to increase with delay in delivering the fetus. Prolongation of the uterine incision to delivery (U-D) interval was associated with a decrease in Ua pH and base excess values. (Ma-Ua) pH and base excess gradients increased with lengthening of the U-D interval. No convincing evidence of awareness during anaesthesia was found during the study. Five patients, appeared to be hallucinated in the immediate post-anaesthetic period. Unpleasant dreams were reported in 5 instances. In this study ketamine appeared to be unassociated with significant biochemical asphyxia, but may have been responsible for some element of drug induced neonatal depression. In view of our own experience and that of other workers, it is suggested that ketamine induction for Caesarean section should be re-evaluated using a lower dose of the drug."}
{"id": "PMID:9840", "title": "Preoperative magnesium trisilicate in infants.", "content": "Three groups, each of forty children aged less than five years and prepared for elective surgery, had their gastric contents' volume and pH measured. The control group showed an incidence of 67-5 per cent with high acidity (pH equal to or less than 2-5). In the second and third groups magnesium trisilicate mixture was given within thirty minutes prior to induction of anaesthesia. The second group, sampled after induction of anaesthesia, showed a marked reduction in acidity, while the third group, sampled at the termination of anaesthesia and surgery, demonstrated that in most cases the neutralization of gastric acidity was still effective.", "contents": "Preoperative magnesium trisilicate in infants. Three groups, each of forty children aged less than five years and prepared for elective surgery, had their gastric contents' volume and pH measured. The control group showed an incidence of 67-5 per cent with high acidity (pH equal to or less than 2-5). In the second and third groups magnesium trisilicate mixture was given within thirty minutes prior to induction of anaesthesia. The second group, sampled after induction of anaesthesia, showed a marked reduction in acidity, while the third group, sampled at the termination of anaesthesia and surgery, demonstrated that in most cases the neutralization of gastric acidity was still effective."}
{"id": "PMID:9841", "title": "A diagram to facilitate the understanding and therapy of mixed acid base disorders.", "content": "A diagram based on in-vivo relationships between arterial hydrogen ion activity (H+) and carbon dioxide tension (PCO2) in primary abnormalities of acid base homeostasis is presented. It is designed to facilitate the interpretation of pH data by including the 95% confidence limits described in patients with simple metabolic and respiratory acid base disorders. These bands have been formulated from observation of simple acid base abnormalities and indicate the appropriate respiratory or renal compensatory response to the primary pH defect. A plot which falls outside these limits therefore indicates the presence of a mixed acid base disorder. The diagram presents a physiological approach to clinical disorders of pH regulation demonstrating maintenance of intra-cellular fluid homeostasis during primary extracellular fluid disturbances. Diagnostic and therapeutic advantages are further illustrated and discussed in six case reports.", "contents": "A diagram to facilitate the understanding and therapy of mixed acid base disorders. A diagram based on in-vivo relationships between arterial hydrogen ion activity (H+) and carbon dioxide tension (PCO2) in primary abnormalities of acid base homeostasis is presented. It is designed to facilitate the interpretation of pH data by including the 95% confidence limits described in patients with simple metabolic and respiratory acid base disorders. These bands have been formulated from observation of simple acid base abnormalities and indicate the appropriate respiratory or renal compensatory response to the primary pH defect. A plot which falls outside these limits therefore indicates the presence of a mixed acid base disorder. The diagram presents a physiological approach to clinical disorders of pH regulation demonstrating maintenance of intra-cellular fluid homeostasis during primary extracellular fluid disturbances. Diagnostic and therapeutic advantages are further illustrated and discussed in six case reports."}
{"id": "PMID:9844", "title": "Molecular mechanisms of nerve block by local anesthetics.", "content": "Local anesthetics block nerve conduction by preventing the increase in membrane permeability to sodium ions that normally leads to a nerve impulse. Among anesthetics containing tertiary amine groups, the cationic, protonated form appears to be more active than the neutral form. However, the neutral forms, as well as uncharged molecules like benzocaine and the aliphatic alcohols, also depress sodium permeability. Studies of single myelinated nerves and squid axons show no direct interaction between calcium ions and local anesthetics, thus disproving theories based on competition between these two agents. Likewise, hypotheses attributing local anesthesia to changes in electrical potentials at the membrane-water interface are disproven by the demonstrated potencies of electrically uncharged anesthetics. Hypotheses that propose that local anesthetics act by expanding the nerve membrane and causing a change in protein conformation that blocks sodium permeability are vague in conception and difficult to test experimentally. Evidence from voltage-clamp studies of single nerve fibers indicates that anesthetic molecules interact with the sodium channels directly, from the inner side of the nerve membrane. Anesthetics bind within sodium channels which have opened during membrane depolarization, preventing the normal sodium ion flux. Anesthetic molecules can dissociate from open channels, but not from channels that remain closed when the nerve is kept at rest. The \"gating\" properties that regulate the opening and closing of sodium channels are reversibly modified during anesthesia. Specifically, the inactivation function responds more slowly and requires more negative membrane potential changes to reach the same values as in unanesthetized nerves. A second, slow inactivation is observed following external application of tertiary amine anesthetics. The selective binding of anesthetics to open sodium channels provides a simple explanation for Wedenski inhibition, in which the block increases with the frequency of nerve impulses. When impulses occur at higher frequencies more sodium channels are open over a period of time comparable to the time necessary for the anesthetic binding reaction, thus more channels are blocked. In addition the changes of the inactivation function result in a longer refractory period and, thus, a decrease of impulse height at higher frequencies. Charged anesthetic molecules may bind in the pore of the sodium channel. Their binding can be modulated by the electrical field in the membrane. The channel has a higher affinity for larger anesthetic molecules, but this may result from their greater hydrophobicity as well as from their size. The binding site favors molecules that contain more polar linkages between the amine group and the aromatic residue. Binding of amine anesthetics is weakly stereospecific and, surprisingly, shows no absolute requirement for the terminal alkyl ammonium moiety present in most local anesthetics...", "contents": "Molecular mechanisms of nerve block by local anesthetics. Local anesthetics block nerve conduction by preventing the increase in membrane permeability to sodium ions that normally leads to a nerve impulse. Among anesthetics containing tertiary amine groups, the cationic, protonated form appears to be more active than the neutral form. However, the neutral forms, as well as uncharged molecules like benzocaine and the aliphatic alcohols, also depress sodium permeability. Studies of single myelinated nerves and squid axons show no direct interaction between calcium ions and local anesthetics, thus disproving theories based on competition between these two agents. Likewise, hypotheses attributing local anesthesia to changes in electrical potentials at the membrane-water interface are disproven by the demonstrated potencies of electrically uncharged anesthetics. Hypotheses that propose that local anesthetics act by expanding the nerve membrane and causing a change in protein conformation that blocks sodium permeability are vague in conception and difficult to test experimentally. Evidence from voltage-clamp studies of single nerve fibers indicates that anesthetic molecules interact with the sodium channels directly, from the inner side of the nerve membrane. Anesthetics bind within sodium channels which have opened during membrane depolarization, preventing the normal sodium ion flux. Anesthetic molecules can dissociate from open channels, but not from channels that remain closed when the nerve is kept at rest. The \"gating\" properties that regulate the opening and closing of sodium channels are reversibly modified during anesthesia. Specifically, the inactivation function responds more slowly and requires more negative membrane potential changes to reach the same values as in unanesthetized nerves. A second, slow inactivation is observed following external application of tertiary amine anesthetics. The selective binding of anesthetics to open sodium channels provides a simple explanation for Wedenski inhibition, in which the block increases with the frequency of nerve impulses. When impulses occur at higher frequencies more sodium channels are open over a period of time comparable to the time necessary for the anesthetic binding reaction, thus more channels are blocked. In addition the changes of the inactivation function result in a longer refractory period and, thus, a decrease of impulse height at higher frequencies. Charged anesthetic molecules may bind in the pore of the sodium channel. Their binding can be modulated by the electrical field in the membrane. The channel has a higher affinity for larger anesthetic molecules, but this may result from their greater hydrophobicity as well as from their size. The binding site favors molecules that contain more polar linkages between the amine group and the aromatic residue. Binding of amine anesthetics is weakly stereospecific and, surprisingly, shows no absolute requirement for the terminal alkyl ammonium moiety present in most local anesthetics..."}
{"id": "PMID:9845", "title": "Further studies of the anti-recall effect of lorazepam: A dose--time--effect relationship.", "content": "The time of onset and duration of the anti-recall action of lorazepam were assessed under clinical conditions by measuring recall and recognition of visual stimuli 24 hours after intravenous administration of lorazepam. The visual stimuli were first presented 5-240 minutes after 2 mg and 5-360 minutes after 4 mg lorazepam. Retrograde amnesia was not produced. Lorazepam, 2 mg, produced a short anti-recall effect (anterograde amnesia) in 50 per cent of the cases, with a latency of 30 minutes and a duration of less than half an hour. Duration and frequency of the anti-recall effect were greater after 4 mg, while the latency was shorter. More than 70 per cent of the individuals tested were amnesic for the visual stimuli 15 minutes to 4 hours after 4 mg lorazepam. Sedation was satisfactory and long-lasting following both doses of lorazepam, but was not related to the anti-recall effect.", "contents": "Further studies of the anti-recall effect of lorazepam: A dose--time--effect relationship. The time of onset and duration of the anti-recall action of lorazepam were assessed under clinical conditions by measuring recall and recognition of visual stimuli 24 hours after intravenous administration of lorazepam. The visual stimuli were first presented 5-240 minutes after 2 mg and 5-360 minutes after 4 mg lorazepam. Retrograde amnesia was not produced. Lorazepam, 2 mg, produced a short anti-recall effect (anterograde amnesia) in 50 per cent of the cases, with a latency of 30 minutes and a duration of less than half an hour. Duration and frequency of the anti-recall effect were greater after 4 mg, while the latency was shorter. More than 70 per cent of the individuals tested were amnesic for the visual stimuli 15 minutes to 4 hours after 4 mg lorazepam. Sedation was satisfactory and long-lasting following both doses of lorazepam, but was not related to the anti-recall effect."}
{"id": "PMID:9846", "title": "Influence of anesthetic agent on survival following hemorrhage.", "content": "One hundred and twenty-eight Sprague-Dawley rats were each anesthetized with one of four anaesthetics and subjected to a standard hemorrhage protocol to determine the effects of anesthetics on survival following hemorrhage. The anesthetics studied were: halothane, 1.26 vol per cent; fluroxene, 4.5 vol per cent; pentobarbital, 50 mg/kg ip; ketamine, 125 mg/kg, im. Mean arterial pressure was conrolled at 40 torr during 60 minutes of hemorrhage. Cumulative survival rates were determined at the end of hemorrhage and 24 hr, 48 hr, 72 hr, and 7 days after hemorrhage. Twenty-four-hour survival rates were: halothane, 50.0 per cent; fluroxene, 56.3 per cent; pentobarbital, 59.4 per cent; ketamine, 84.4 per cent. Seven-day survival rates were: halothane, 46.9 per cent; fluroxene, 18.7 per cent; pentobarbital, 53.1 per cent; ketamine; 81.3 per cent. Survival rates were significantly higher (P less than 0.05) in animals anesthetized with ketamine compared with survival rates associated with the other anesthetics. Long-term (72-hr and seven-day) survival rates were significantly (P less than 0.05) lower in animals anesthetized with fluroxene. Microscopic examination of livers and small intestines revealed significantly fewer (P less than 0.05) athologic changes in the splanchnic organs of hemorrhaged rats anesthetized with ketamine compared with animals anesthetized with the other drugs.", "contents": "Influence of anesthetic agent on survival following hemorrhage. One hundred and twenty-eight Sprague-Dawley rats were each anesthetized with one of four anaesthetics and subjected to a standard hemorrhage protocol to determine the effects of anesthetics on survival following hemorrhage. The anesthetics studied were: halothane, 1.26 vol per cent; fluroxene, 4.5 vol per cent; pentobarbital, 50 mg/kg ip; ketamine, 125 mg/kg, im. Mean arterial pressure was conrolled at 40 torr during 60 minutes of hemorrhage. Cumulative survival rates were determined at the end of hemorrhage and 24 hr, 48 hr, 72 hr, and 7 days after hemorrhage. Twenty-four-hour survival rates were: halothane, 50.0 per cent; fluroxene, 56.3 per cent; pentobarbital, 59.4 per cent; ketamine, 84.4 per cent. Seven-day survival rates were: halothane, 46.9 per cent; fluroxene, 18.7 per cent; pentobarbital, 53.1 per cent; ketamine; 81.3 per cent. Survival rates were significantly higher (P less than 0.05) in animals anesthetized with ketamine compared with survival rates associated with the other anesthetics. Long-term (72-hr and seven-day) survival rates were significantly (P less than 0.05) lower in animals anesthetized with fluroxene. Microscopic examination of livers and small intestines revealed significantly fewer (P less than 0.05) athologic changes in the splanchnic organs of hemorrhaged rats anesthetized with ketamine compared with animals anesthetized with the other drugs."}
{"id": "PMID:9851", "title": "[Structure of the interalveolar wall].", "content": "The wall, which unites as well as separates two contiguous pulmonary alveoli is composed of: - a conjuntival partition, the veritable skeleton of the wall, which is occupied, to the largest extent, by capillary blood vessels. Between the capillaries, conjunctival cells are dispursed: fibrocytes, fibroblasts and histiocytes, of which some can be mobilised, transformed into macrophages, and penetrate into the alveolar lumen; - modified epithelial cells, whose very thin, vast expansions cover the conjunctival partition; - a liquid film, 0.2 mu in thickness, which separates the epithelial cells, or pneumocytes from the alveolar air. Numerous physiological implications result from this organisation.", "contents": "[Structure of the interalveolar wall]. The wall, which unites as well as separates two contiguous pulmonary alveoli is composed of: - a conjuntival partition, the veritable skeleton of the wall, which is occupied, to the largest extent, by capillary blood vessels. Between the capillaries, conjunctival cells are dispursed: fibrocytes, fibroblasts and histiocytes, of which some can be mobilised, transformed into macrophages, and penetrate into the alveolar lumen; - modified epithelial cells, whose very thin, vast expansions cover the conjunctival partition; - a liquid film, 0.2 mu in thickness, which separates the epithelial cells, or pneumocytes from the alveolar air. Numerous physiological implications result from this organisation."}
{"id": "PMID:9852", "title": "[Pulmonary edemas of drownings].", "content": "Patients who are victims of near drowning in fresh water or salt water very frequently have acute edema of the lung which occurs either immediately, or after a free interval of variable duration. The mechanism of this edema is explained, in near drowning in salt water, by the hyperosmolarity of the alveolar fluid leading to a seeping of plasma from the capillaries in the alveoli. In the case of near drowning in fresh water, it is on the contrary the inhaled liquid which passes into the circulation, therby leading to immediate hypervolemia, but this overload is only transitory and is not responsible for the pulmonary edema which occurs later is not accompanied by a rise in pulmonary capillary pressure. It is therefore a lesional edema as is certified by the anatomopathological modifications found in the lungs of drowned patients. Therapeutic management must therefore take into consideration this physiopathology of acute edema of the lung in the drowned.", "contents": "[Pulmonary edemas of drownings]. Patients who are victims of near drowning in fresh water or salt water very frequently have acute edema of the lung which occurs either immediately, or after a free interval of variable duration. The mechanism of this edema is explained, in near drowning in salt water, by the hyperosmolarity of the alveolar fluid leading to a seeping of plasma from the capillaries in the alveoli. In the case of near drowning in fresh water, it is on the contrary the inhaled liquid which passes into the circulation, therby leading to immediate hypervolemia, but this overload is only transitory and is not responsible for the pulmonary edema which occurs later is not accompanied by a rise in pulmonary capillary pressure. It is therefore a lesional edema as is certified by the anatomopathological modifications found in the lungs of drowned patients. Therapeutic management must therefore take into consideration this physiopathology of acute edema of the lung in the drowned."}
{"id": "PMID:9853", "title": "[Pulmonary edemas. Classification and mechanisms].", "content": "Water exchanges in the lung under physiological conditions, are still badly known. Starling's classical equation is a too simplified view of the phenomenon. In addition, a certain number of its factors are badly determined. Such is the case with the hydrostatic pressure and the oncotic pressure of the interstitium. In pathological conditions secondary edema is opposed to lesions of the alveolocapillary membrane and hemodynamic edema where the increase in intravascular pressure increases a loss of liquid between the junctions of the endothelial cells. Between these two situations there are edemas, of which the mechanism is still subject to discussion, for example altitude edema, edema in heroin addicts, neurogenic edema.", "contents": "[Pulmonary edemas. Classification and mechanisms]. Water exchanges in the lung under physiological conditions, are still badly known. Starling's classical equation is a too simplified view of the phenomenon. In addition, a certain number of its factors are badly determined. Such is the case with the hydrostatic pressure and the oncotic pressure of the interstitium. In pathological conditions secondary edema is opposed to lesions of the alveolocapillary membrane and hemodynamic edema where the increase in intravascular pressure increases a loss of liquid between the junctions of the endothelial cells. Between these two situations there are edemas, of which the mechanism is still subject to discussion, for example altitude edema, edema in heroin addicts, neurogenic edema."}
{"id": "PMID:9854", "title": "[High altitude acute pulmonary edema (author's transl)].", "content": "HAAPE has been recognised only recently but is of real interest as much from the clinical as well as the dogmatic stand-point owing to the complexity of its physiopathological findings. It is encountered at altitudes higher than 4,000 meters either during a first contact or in natives returning from low altitude zones. There is an individual or even racial susceptibility.", "contents": "[High altitude acute pulmonary edema (author's transl)]. HAAPE has been recognised only recently but is of real interest as much from the clinical as well as the dogmatic stand-point owing to the complexity of its physiopathological findings. It is encountered at altitudes higher than 4,000 meters either during a first contact or in natives returning from low altitude zones. There is an individual or even racial susceptibility."}
{"id": "PMID:9855", "title": "[Pulmonary edemas of infectious origin].", "content": "Diffuse pulmonary edema, capable of arising in the absence of hemodynamic disorders is rare in infectious disease. They take on two different clinical appearances: a) acute edema of the lung with the syndrome of asphysia, b) a subacute dyspneic pneumonia with hypoxemia and hypo or normocapnia. These initial disorders can be followed by progressive respiratory failure secondary to the development of diffuse interstitial lesions with fibrosis and intra-alveolar hyaline deposits. The bronchiolo-alveolar lesions which induce a fibrin rich exudate are directly caused by the patogenic agent: myxovirus, essentially influenzae, and more rarely adeno or herpes virus. The role of bacteria and of certain parasites is more debateable.", "contents": "[Pulmonary edemas of infectious origin]. Diffuse pulmonary edema, capable of arising in the absence of hemodynamic disorders is rare in infectious disease. They take on two different clinical appearances: a) acute edema of the lung with the syndrome of asphysia, b) a subacute dyspneic pneumonia with hypoxemia and hypo or normocapnia. These initial disorders can be followed by progressive respiratory failure secondary to the development of diffuse interstitial lesions with fibrosis and intra-alveolar hyaline deposits. The bronchiolo-alveolar lesions which induce a fibrin rich exudate are directly caused by the patogenic agent: myxovirus, essentially influenzae, and more rarely adeno or herpes virus. The role of bacteria and of certain parasites is more debateable."}
{"id": "PMID:9856", "title": "[Hemodynamic data in lesional pulmonary edemas].", "content": "Pulmonary edema due to disorders in alveolo-capillary permeability (or lesional) are differentiated from hemodynamic pulmonary edema by the fact that they arise in spite of normal pulmonary capillary pressure (PCP). A hemodynamic study was carried out in 42 cases of lesional P.E. The PCP was normal whatever the date of the examination and the gravity of the P.E. Pulmonary arterial hypertension was only found in the presence of frank hypoxemia and disappeared with the correction of the latter. If there was no hemodynamic profile due to P.E. itself, its etiology sometimes induced a hyperkinetic or hypovolemic syndrome. Finally it was apparent that PCP was significantly higher- although normal- at the initial stage than after 6 hours of P.E.; that an elevation in PCP of only a few mm Hg by the perfusion of colloids aggravated the P.E., that despite the normal value for the PCP dehydration evidently improved hematosis. Thus this study confirms that numerous cases of P.E. can occur while the PCP remains normal. It also confirms the noxious nature of too abundant perfusions in these cases and the effectiveness of dehydration.", "contents": "[Hemodynamic data in lesional pulmonary edemas]. Pulmonary edema due to disorders in alveolo-capillary permeability (or lesional) are differentiated from hemodynamic pulmonary edema by the fact that they arise in spite of normal pulmonary capillary pressure (PCP). A hemodynamic study was carried out in 42 cases of lesional P.E. The PCP was normal whatever the date of the examination and the gravity of the P.E. Pulmonary arterial hypertension was only found in the presence of frank hypoxemia and disappeared with the correction of the latter. If there was no hemodynamic profile due to P.E. itself, its etiology sometimes induced a hyperkinetic or hypovolemic syndrome. Finally it was apparent that PCP was significantly higher- although normal- at the initial stage than after 6 hours of P.E.; that an elevation in PCP of only a few mm Hg by the perfusion of colloids aggravated the P.E., that despite the normal value for the PCP dehydration evidently improved hematosis. Thus this study confirms that numerous cases of P.E. can occur while the PCP remains normal. It also confirms the noxious nature of too abundant perfusions in these cases and the effectiveness of dehydration."}
{"id": "PMID:9858", "title": "[Blood gas determination and calculation of shunts in nonhemodynamic pulmonary edemas].", "content": "Qs/Qt is usually determined by the \"oxygen\" method. The standard equation for calculation of percentage shunts is therefore: (see article) In the case for an FiO2 of I and when PaO2 is greater than 150 mm Hg, the equation can be expressed in terms of the difference in partial pressures of oxygen between the alveolus and the artery: (see article) The determination of Qs/Qt then necessitates, apart from calculation of PaO2 measurement of the O2 content of mixed venous blood, taken from the pulmonary artery. When an indwelling catheter for the sampling of mixed venous blood is not available, samples of superior vena cava blood can be used instead. The error thereby introduced into the calculation of Qs/Qt is debatable. Strictly, only the sampling of mixed venous blood permits precise determination of Qs/Qt. As long as the variations in Qs/Qt, more than its real value at a give time, are worth supervising, superior vena cava blood gives a rather satisfactory approximation. Various graphs relating Qs/Qt to PaO2 or to the alveolo-arterial difference have been proposed and are discussed. The other methods of determining Qs/Qt are also looked at. The value of determination of the shunt during non-hemodynamic edema, and especially in the patient under artificial ventilation with P.E.E.P., is emphasised.", "contents": "[Blood gas determination and calculation of shunts in nonhemodynamic pulmonary edemas]. Qs/Qt is usually determined by the \"oxygen\" method. The standard equation for calculation of percentage shunts is therefore: (see article) In the case for an FiO2 of I and when PaO2 is greater than 150 mm Hg, the equation can be expressed in terms of the difference in partial pressures of oxygen between the alveolus and the artery: (see article) The determination of Qs/Qt then necessitates, apart from calculation of PaO2 measurement of the O2 content of mixed venous blood, taken from the pulmonary artery. When an indwelling catheter for the sampling of mixed venous blood is not available, samples of superior vena cava blood can be used instead. The error thereby introduced into the calculation of Qs/Qt is debatable. Strictly, only the sampling of mixed venous blood permits precise determination of Qs/Qt. As long as the variations in Qs/Qt, more than its real value at a give time, are worth supervising, superior vena cava blood gives a rather satisfactory approximation. Various graphs relating Qs/Qt to PaO2 or to the alveolo-arterial difference have been proposed and are discussed. The other methods of determining Qs/Qt are also looked at. The value of determination of the shunt during non-hemodynamic edema, and especially in the patient under artificial ventilation with P.E.E.P., is emphasised."}
{"id": "PMID:9859", "title": "[Continuous measurement, using 2 isotopes, of extravascular pulmonary water. Application of a new method or the analysis of supply and pulmonary capillary filtration in normal man].", "content": "Measurement of pulmonary interstitial fluid may be useful in clinical medicine for early diagnosis or measurement of interstitial and/or alveolar pulmonary edema. A modification of the double dilution method of CHINARD and GORESKY is proposed. Compared to previous methods, this technique, using two isotopes gamma  emitters, is rapid, simple, reproductible and may be repeated. The values obtained in normal subjects at rest 3.5 +/- 0.5 ml/kg, are comparable with those of other authors. They increase considerably in cases of fluid load.", "contents": "[Continuous measurement, using 2 isotopes, of extravascular pulmonary water. Application of a new method or the analysis of supply and pulmonary capillary filtration in normal man]. Measurement of pulmonary interstitial fluid may be useful in clinical medicine for early diagnosis or measurement of interstitial and/or alveolar pulmonary edema. A modification of the double dilution method of CHINARD and GORESKY is proposed. Compared to previous methods, this technique, using two isotopes gamma  emitters, is rapid, simple, reproductible and may be repeated. The values obtained in normal subjects at rest 3.5 +/- 0.5 ml/kg, are comparable with those of other authors. They increase considerably in cases of fluid load."}
{"id": "PMID:9860", "title": "[Pulmonary water and thoracic impedance. Evaluation of a measurement technic].", "content": "We measured transthoracic electrical impedance in 17 anesthetized and mechanically ventilated dogs with a four-electrode system. A current (5 KHZ, 50 mu A) is injected and detected at axillary levels. Transthoracic impedance was 67 +/- 14 ohms (S.D.) with insignificant shifts in control animals. Pulmonary edemas were induced by saline and dextrose overloads with large but opposite variations in impedance. Fifty to hundred per cent increases in total lung water content (determined at autopsy) were induced by intravenous injection of alloxan or instillation of endotracheal saline. Significant but small decreases in impedance followed. Validity of experimental pulmonary edemas with or without blood resistivity and pulmonary blood volume changes is discussed.", "contents": "[Pulmonary water and thoracic impedance. Evaluation of a measurement technic]. We measured transthoracic electrical impedance in 17 anesthetized and mechanically ventilated dogs with a four-electrode system. A current (5 KHZ, 50 mu A) is injected and detected at axillary levels. Transthoracic impedance was 67 +/- 14 ohms (S.D.) with insignificant shifts in control animals. Pulmonary edemas were induced by saline and dextrose overloads with large but opposite variations in impedance. Fifty to hundred per cent increases in total lung water content (determined at autopsy) were induced by intravenous injection of alloxan or instillation of endotracheal saline. Significant but small decreases in impedance followed. Validity of experimental pulmonary edemas with or without blood resistivity and pulmonary blood volume changes is discussed."}
{"id": "PMID:9861", "title": "[Regional distribution of pulmonary perfusion during fluid overload in man].", "content": "The effects of a fluid vascular overload (Dextran 40,000, 10 p. 100, 44 +/- ml/kg/45 min) were studied in 9 normal subjects in the upright position. The following were found: an increase in pulmonary blood volume (+30 p. 100), and in extravascular pulmonary water (+ 70 p. 100), a significant fall in pulmonary compliance and an increase in bronchial resistance. Radio-isotopic study of the regional distribution of pulmonary perfusion showed a clear inversion with decrease in perfusion at the bases and increase at the apices. From the theoretical standpoint, this inversion of distribution of perfusion can be due to hypoxic vasoconstriction in the lung bases, to an increase in flow and entry pressures recruiting apical vessels or to a perivascular compressive edema in the lower parts of the lungs. Different modifications complementing the initial experimental protocol tend to prove that it is this latter reason which is essentially at the origin of the inversion in regional distribution of pulmonary perfusion.", "contents": "[Regional distribution of pulmonary perfusion during fluid overload in man]. The effects of a fluid vascular overload (Dextran 40,000, 10 p. 100, 44 +/- ml/kg/45 min) were studied in 9 normal subjects in the upright position. The following were found: an increase in pulmonary blood volume (+30 p. 100), and in extravascular pulmonary water (+ 70 p. 100), a significant fall in pulmonary compliance and an increase in bronchial resistance. Radio-isotopic study of the regional distribution of pulmonary perfusion showed a clear inversion with decrease in perfusion at the bases and increase at the apices. From the theoretical standpoint, this inversion of distribution of perfusion can be due to hypoxic vasoconstriction in the lung bases, to an increase in flow and entry pressures recruiting apical vessels or to a perivascular compressive edema in the lower parts of the lungs. Different modifications complementing the initial experimental protocol tend to prove that it is this latter reason which is essentially at the origin of the inversion in regional distribution of pulmonary perfusion."}
{"id": "PMID:9862", "title": "[Pulmonary edemas. Anatomic study].", "content": "Whatever the etiology of pulmonary edema, i.e. increase in intrapulmonary water, edema passes through three, moreover intricate phases: 1- intracellular edema clearly visible in the type 1 pneumocyte. This intracellular edema appears at the same time as: 2- interstitial edema; that which appears when: 3- numerous vesicules of pinocytosis and separation of the capillary endothelial cells account for it; 4- intra-alveolar edema itself appears later and corresponds to the major clinical phase of pulmonary edema. There is nothing surprising about this as the cellular functions of pneumocytes are impervious as can be shown for example by studies carried out with tracers. This intracellular alveolar edema seems to have two different aspects depending on whether the experimental conditions create an acute or sub-acute pathology. In the acute form, the edema is poor in lipids and in proteins. In the sub-acute of chronic forms, it is on the contrary very rich in them. 5-In the last phase, a veritable desquamation of the pneumocytes then of the endothelial cells is produced which is very frequently lethal. If survival occurs, two sorts of lesions are found: -colonisation of the alveolar surface with type II pneumocytes; - occurrence of possible intersitial fibrosis. The remarkable fact is that such lesions are visible in a more or less identical manner in all cases of pulmonary edema, whether they be hemodynamic or lesional. The morphology does not confirm this physiopathological distinction which is moreover questionable as all pulmonary edema become lesional sooner or later.", "contents": "[Pulmonary edemas. Anatomic study]. Whatever the etiology of pulmonary edema, i.e. increase in intrapulmonary water, edema passes through three, moreover intricate phases: 1- intracellular edema clearly visible in the type 1 pneumocyte. This intracellular edema appears at the same time as: 2- interstitial edema; that which appears when: 3- numerous vesicules of pinocytosis and separation of the capillary endothelial cells account for it; 4- intra-alveolar edema itself appears later and corresponds to the major clinical phase of pulmonary edema. There is nothing surprising about this as the cellular functions of pneumocytes are impervious as can be shown for example by studies carried out with tracers. This intracellular alveolar edema seems to have two different aspects depending on whether the experimental conditions create an acute or sub-acute pathology. In the acute form, the edema is poor in lipids and in proteins. In the sub-acute of chronic forms, it is on the contrary very rich in them. 5-In the last phase, a veritable desquamation of the pneumocytes then of the endothelial cells is produced which is very frequently lethal. If survival occurs, two sorts of lesions are found: -colonisation of the alveolar surface with type II pneumocytes; - occurrence of possible intersitial fibrosis. The remarkable fact is that such lesions are visible in a more or less identical manner in all cases of pulmonary edema, whether they be hemodynamic or lesional. The morphology does not confirm this physiopathological distinction which is moreover questionable as all pulmonary edema become lesional sooner or later."}
{"id": "PMID:9863", "title": "[Contribution of radiology in nonhemodynamic pulmonary edemas].", "content": "The radiological appearances of non-hemodynamic, lesional edema are univoco; interstitial-type pictures, alveolar-type pictures, either successively or combined, in terms of the intensity or duration of the alveolo-capillary membrane lesions. Inflation of the interstitial medium is reflected by the appearance of Kerley B lines, haziness of the vascular contours and sometimes an axillary bordering line due to subpleural edema. Capillary congestion with increase in permeability especially to proteins and the tearing of connective tissue explains these pictures. In the following stage, edema is alveolar with hazy diffuse, unorganised and confluent opacities. These opacities can predominate in the bases, or take on a butterfly-wing distribution. At this stage atelectatic lesions can be superadded due to inactivation of surfactant. Finally, in the later periods the appearance of interstitial pulmonary fibrosis with fibrinous deposits and fibroblastic proliferation can be noted. The chest X-ray is the objective reflection of the disorders; in enables the making of a diagnosis, and the drawing up of a complete check of the lesions and supervision of its course.", "contents": "[Contribution of radiology in nonhemodynamic pulmonary edemas]. The radiological appearances of non-hemodynamic, lesional edema are univoco; interstitial-type pictures, alveolar-type pictures, either successively or combined, in terms of the intensity or duration of the alveolo-capillary membrane lesions. Inflation of the interstitial medium is reflected by the appearance of Kerley B lines, haziness of the vascular contours and sometimes an axillary bordering line due to subpleural edema. Capillary congestion with increase in permeability especially to proteins and the tearing of connective tissue explains these pictures. In the following stage, edema is alveolar with hazy diffuse, unorganised and confluent opacities. These opacities can predominate in the bases, or take on a butterfly-wing distribution. At this stage atelectatic lesions can be superadded due to inactivation of surfactant. Finally, in the later periods the appearance of interstitial pulmonary fibrosis with fibrinous deposits and fibroblastic proliferation can be noted. The chest X-ray is the objective reflection of the disorders; in enables the making of a diagnosis, and the drawing up of a complete check of the lesions and supervision of its course."}
{"id": "PMID:9864", "title": "[Severity factors and diagnosis of nonhemodynamic pulmonary edemas].", "content": "This syndrome is characterised by changes in the pulmonary capillary bed allowing filtration of edema fluid rich in proteins. It provokes an alveolo-capillary block and a fall in compliance. Positive diagnosis is envisaged from the clinical circumstances implicating a change in the pulmonary capillaries (blast, shock, microemboli). The fall in pO2 is early and intense. The fall in compliance is later and leads to hypoventilation necessitating ventilatory assistance. Diffuse radiological opacification of both pulmonary fields is characteristics, in its appearance and also in its prolonged course. In the differential diagnosis one should try to eliminate acute pulmonary edema and refractory hypoxia of bronchogenic origin. Prognosis of the condition is fixed by the course (of the pO2, of possible hypoventilation, of the radiological pictures), under treatment. Although persistance of the syndrome for more than one or two weeks is of bad prognosis, cases have been known to progress for more than three weeks and to heal leaving no after-effects. The syndrome can be complicated by cardiac incompetence, organic renal failure, which again aggravate the prognosis.", "contents": "[Severity factors and diagnosis of nonhemodynamic pulmonary edemas]. This syndrome is characterised by changes in the pulmonary capillary bed allowing filtration of edema fluid rich in proteins. It provokes an alveolo-capillary block and a fall in compliance. Positive diagnosis is envisaged from the clinical circumstances implicating a change in the pulmonary capillaries (blast, shock, microemboli). The fall in pO2 is early and intense. The fall in compliance is later and leads to hypoventilation necessitating ventilatory assistance. Diffuse radiological opacification of both pulmonary fields is characteristics, in its appearance and also in its prolonged course. In the differential diagnosis one should try to eliminate acute pulmonary edema and refractory hypoxia of bronchogenic origin. Prognosis of the condition is fixed by the course (of the pO2, of possible hypoventilation, of the radiological pictures), under treatment. Although persistance of the syndrome for more than one or two weeks is of bad prognosis, cases have been known to progress for more than three weeks and to heal leaving no after-effects. The syndrome can be complicated by cardiac incompetence, organic renal failure, which again aggravate the prognosis."}
{"id": "PMID:9865", "title": "[Reduction and anti-inflammatory technics in non-hemodynamic pulmonary edemas].", "content": "All hypervolemia or any decrease in plasma oncotic pressure leads to deterioration in lesional pulmonary edema. The aim of albumin infusions is to restore the plasma oncotic pressure and to oppose the passage of water into the extravascular space. This therapy is however debatable owing to the abnormal increase in the permeability of the alveolo-capillary membrane to proteins. Diuretics enable one to lower the volemia and to maintain the pulmonary capillary pressure at its minimum level. However, strict hemodynamic supervision is absolutely necessary. Cortico-steroids have been recommended without serious physiopathological justification. However, they have a preventive action on interstitial edema in endotoxic shock.", "contents": "[Reduction and anti-inflammatory technics in non-hemodynamic pulmonary edemas]. All hypervolemia or any decrease in plasma oncotic pressure leads to deterioration in lesional pulmonary edema. The aim of albumin infusions is to restore the plasma oncotic pressure and to oppose the passage of water into the extravascular space. This therapy is however debatable owing to the abnormal increase in the permeability of the alveolo-capillary membrane to proteins. Diuretics enable one to lower the volemia and to maintain the pulmonary capillary pressure at its minimum level. However, strict hemodynamic supervision is absolutely necessary. Cortico-steroids have been recommended without serious physiopathological justification. However, they have a preventive action on interstitial edema in endotoxic shock."}
{"id": "PMID:9866", "title": "[Justification, methods and indications for positive-pressure respiration in controlled and spontaneous ventilation in lesional pulmonary edeman].", "content": "Proposed since 1938 as a treatment for pulmonary edema, continuous positive pressure ventilation (PPP) still called teleexpiratory positive pressure in France (PPTE) and  \"Positive End Expiratory Pressure\" (PEEP) or even \"Continuous Pressure  Breathing\" (CPPB) in Anglo-Saxon countries, has taken a place in the first line of therapy in refractory hypoxia and particulary when the latter originate from lesional pulmonary edema. The aim of PPP is to open up the alveolar territories by calling on their elastic properties, to fight against micro-atelectasis and bronchial collapse, to diminish the closing volume, to increase the FRC, thereby improve VA/Qc, decrease Qs/Qt and increase PaO2. Furthermore, in the particular case of pulmonary edema, PPP acts against the hydrostatic pressure by increasing the external component of the transmural pressure and by evening out pulmonary capillary blood flow.", "contents": "[Justification, methods and indications for positive-pressure respiration in controlled and spontaneous ventilation in lesional pulmonary edeman]. Proposed since 1938 as a treatment for pulmonary edema, continuous positive pressure ventilation (PPP) still called teleexpiratory positive pressure in France (PPTE) and  \"Positive End Expiratory Pressure\" (PEEP) or even \"Continuous Pressure  Breathing\" (CPPB) in Anglo-Saxon countries, has taken a place in the first line of therapy in refractory hypoxia and particulary when the latter originate from lesional pulmonary edema. The aim of PPP is to open up the alveolar territories by calling on their elastic properties, to fight against micro-atelectasis and bronchial collapse, to diminish the closing volume, to increase the FRC, thereby improve VA/Qc, decrease Qs/Qt and increase PaO2. Furthermore, in the particular case of pulmonary edema, PPP acts against the hydrostatic pressure by increasing the external component of the transmural pressure and by evening out pulmonary capillary blood flow."}
{"id": "PMID:9867", "title": "[Treatment of fulminating lesional edemas using extracorporeal circulation with a membrane oxygenator].", "content": "Recourse to extra-corporeal oxygenation is legitimate in certain cases of fulminating pulmonary edema, with refractory hypoxemia, particularly when the early onset of the hemodynamic condition and the severity of the hypoxemia do not permit the carrying out of dehydration. Veno-arterial diversion then permits: --the ensuring of half or two thirds of the oxygen consumption; --the restoration of systemic hemodynamics by arterial reinjection; --the very rapid reduction of pulmonary edema by \"decompressing\" the pulmonary artery.", "contents": "[Treatment of fulminating lesional edemas using extracorporeal circulation with a membrane oxygenator]. Recourse to extra-corporeal oxygenation is legitimate in certain cases of fulminating pulmonary edema, with refractory hypoxemia, particularly when the early onset of the hemodynamic condition and the severity of the hypoxemia do not permit the carrying out of dehydration. Veno-arterial diversion then permits: --the ensuring of half or two thirds of the oxygen consumption; --the restoration of systemic hemodynamics by arterial reinjection; --the very rapid reduction of pulmonary edema by \"decompressing\" the pulmonary artery."}
{"id": "PMID:9868", "title": "[Present statues of lung transplantation (author's transl)].", "content": "It is difficult to sum up the justifications for pulmonary transplantation in man as out of 34 cases carried out up to now only the patient DEROM, has survived 10 months. In fact, analysis shows that all of the other cases cannot be taken into consideration, as there were technical problems, or the receivers were nearly in the threws of death and this was the case of the patient SALVATOR. Two important problems remain to be resolved: First of all that of obtaining grafts in good condition. In fact the sole source of donors remains irreversible comas, and it is known that after 24 hours of artificial respiration the lung has undergone irreparable damage. It is therefore necessary to develop a reliable method for preservation. Present experimental results show that lungs preserved for 48 hours and regrafted into other animals are not only functional, in the immediate, but the scintigraphic scanning graphs after a month, are comparable with those in control animals. Studies of coagulation have demonstrated that pulmonary rejection is characterised before infiltration by mononuclear cells, by major coagulation disorders. In the treated animals, rejection crises are preceded a few days earlier by hypercoagulability and a fall in circulating platelets. These findings have enabled one, by the addition of appropriate anti-coagulant treatment, to overcome the rejection crises- without any other therapy than the basic classical treatment- (Immuran + corticosteroids). Under these conditions, the few specialised centres are therefore authorised to again attempt human pulmonary transplantation.", "contents": "[Present statues of lung transplantation (author's transl)]. It is difficult to sum up the justifications for pulmonary transplantation in man as out of 34 cases carried out up to now only the patient DEROM, has survived 10 months. In fact, analysis shows that all of the other cases cannot be taken into consideration, as there were technical problems, or the receivers were nearly in the threws of death and this was the case of the patient SALVATOR. Two important problems remain to be resolved: First of all that of obtaining grafts in good condition. In fact the sole source of donors remains irreversible comas, and it is known that after 24 hours of artificial respiration the lung has undergone irreparable damage. It is therefore necessary to develop a reliable method for preservation. Present experimental results show that lungs preserved for 48 hours and regrafted into other animals are not only functional, in the immediate, but the scintigraphic scanning graphs after a month, are comparable with those in control animals. Studies of coagulation have demonstrated that pulmonary rejection is characterised before infiltration by mononuclear cells, by major coagulation disorders. In the treated animals, rejection crises are preceded a few days earlier by hypercoagulability and a fall in circulating platelets. These findings have enabled one, by the addition of appropriate anti-coagulant treatment, to overcome the rejection crises- without any other therapy than the basic classical treatment- (Immuran + corticosteroids). Under these conditions, the few specialised centres are therefore authorised to again attempt human pulmonary transplantation."}
{"id": "PMID:9869", "title": "[Vaso-active substances and pulmonary circulation].", "content": "This study reveals the main vaso-active substances which pass through the lung, by studying in each case the extra-pulmonary of pulmonary origin, the effects of the lung on these substances: capture, discharge, transformation, and the effects of these substances on the lung. Eight groups of substances are studied: mediators of the sympatho-adrenergic system, substances interfering with adrenergic agents, acetyl-choline, serotonin, angiotensin, histamine, kinins, and prostaglandins. The lung behaves either as a neutral organ, or a filtering organ, or a filtering organ, or a secreting organ for these substances. In this way it strangely resembles the kidney. The pulmonary circulation is not completely comprised of simple reaction. It is capable of internal adjustement and redistribution under the effect of these substances. Pulmonary edema probably will always remain difficult to their mechanism of production, in so far as can be estimated from the multitude of substances. It is still rather a delicate matter to distinguish between edema-generating phenomena and phenomena which are secondary to the edema itself.", "contents": "[Vaso-active substances and pulmonary circulation]. This study reveals the main vaso-active substances which pass through the lung, by studying in each case the extra-pulmonary of pulmonary origin, the effects of the lung on these substances: capture, discharge, transformation, and the effects of these substances on the lung. Eight groups of substances are studied: mediators of the sympatho-adrenergic system, substances interfering with adrenergic agents, acetyl-choline, serotonin, angiotensin, histamine, kinins, and prostaglandins. The lung behaves either as a neutral organ, or a filtering organ, or a filtering organ, or a secreting organ for these substances. In this way it strangely resembles the kidney. The pulmonary circulation is not completely comprised of simple reaction. It is capable of internal adjustement and redistribution under the effect of these substances. Pulmonary edema probably will always remain difficult to their mechanism of production, in so far as can be estimated from the multitude of substances. It is still rather a delicate matter to distinguish between edema-generating phenomena and phenomena which are secondary to the edema itself."}
{"id": "PMID:9870", "title": "[Pulmonary edema due to shock, fat embolism, disseminated intravascular coagulation and post extracorporeal circulation].", "content": "The appearance of lesional edema in the region of the alveolar wall constitues the initial phenomenon of involvement of the pulmonary parenchyma during shock lung, fat embolism, DIC and post perfusion lung syndrome. The alveolar septum reacts in a monomorphous manner to these various agressions, although the responsible physiopathological factors are numerous and varied. The lung in E.C.C. represents a vertiable experimental post-agressive lung. It has been studied in man from the clinical, radiological, hemodynamic and anatomopathological standpoints. The modifications found enable one to better understand the etiological factors intervening in the other post-agressive lungs.", "contents": "[Pulmonary edema due to shock, fat embolism, disseminated intravascular coagulation and post extracorporeal circulation]. The appearance of lesional edema in the region of the alveolar wall constitues the initial phenomenon of involvement of the pulmonary parenchyma during shock lung, fat embolism, DIC and post perfusion lung syndrome. The alveolar septum reacts in a monomorphous manner to these various agressions, although the responsible physiopathological factors are numerous and varied. The lung in E.C.C. represents a vertiable experimental post-agressive lung. It has been studied in man from the clinical, radiological, hemodynamic and anatomopathological standpoints. The modifications found enable one to better understand the etiological factors intervening in the other post-agressive lungs."}
{"id": "PMID:9871", "title": "[Pulmonary surfactants. Generalities].", "content": "The alveolar wall on contact with air can be compared with a biological air-liquide interface. As with all interfaces, there are therefore superficial forces which tend to reduce the surface to a minimum. In the case of a pulmonary alveolus with a spherical surface, these forces are at the origin of an internal pressure excess dependent on the radius of the alveolus and on the superficial tension related to the nature of the interface. Owing to the disparity in the alveolar radii, under these conditions the smaller alveoli would collapse to the benefit of a larger one, the pressure being lower and lower in the latter. In addition, at any time in the respiratory cycles, this surpression must be negligible in order to avoid rupture of the equilibrium of the forces exerted on the alveolar wall. Consequently, it is necessary that this air-alveolar wall interface should have a superficial tension on the one hand variable with the surface, and on the other hand always very low. Owing to the demonstration of large concentrations of phospholipid in this area, it can be thought that a superficial film is substituted at the air-biological liquid interface and owing to this fact effectively has superficial properties necessary for alveolar stability. The \"surface-tensio-active\" effect of this film lead to the giving of the name of \"surfactant\" to these constituents as a whole.", "contents": "[Pulmonary surfactants. Generalities]. The alveolar wall on contact with air can be compared with a biological air-liquide interface. As with all interfaces, there are therefore superficial forces which tend to reduce the surface to a minimum. In the case of a pulmonary alveolus with a spherical surface, these forces are at the origin of an internal pressure excess dependent on the radius of the alveolus and on the superficial tension related to the nature of the interface. Owing to the disparity in the alveolar radii, under these conditions the smaller alveoli would collapse to the benefit of a larger one, the pressure being lower and lower in the latter. In addition, at any time in the respiratory cycles, this surpression must be negligible in order to avoid rupture of the equilibrium of the forces exerted on the alveolar wall. Consequently, it is necessary that this air-alveolar wall interface should have a superficial tension on the one hand variable with the surface, and on the other hand always very low. Owing to the demonstration of large concentrations of phospholipid in this area, it can be thought that a superficial film is substituted at the air-biological liquid interface and owing to this fact effectively has superficial properties necessary for alveolar stability. The \"surface-tensio-active\" effect of this film lead to the giving of the name of \"surfactant\" to these constituents as a whole."}
{"id": "PMID:9872", "title": "[Acute neurogenic pulmonary edema].", "content": "Neurogenic edema, in the strict sense of the term, has at the present time practically not benefitted from precise hemodynamic investigations in human clinical practice, and owing to this fact, authors still classify them under the heading \"mixed edema or of unknown pathogenesis\". In contrast with this lack of information in man, animal experimental works are surprising by their coherence and the experimental facility of producing neurogenic edema (cranial hypertension by a small inflatable balloon and cisternal infection of fibrin). If one excludes the now ancient vagal theories (CAMERON 1949; CAMPBELL, 1949) which were never confirmed, all of the most recent experimental works (SARNOFF, 1952; DUCKER, 1968; LUISADA, 1967; MORITZ, 1974) confirm the adrenergic disorder of central origin during neurogenic A.P.E. which from the hemodynamic standpoint is like an authentic hemodynamic A.P.E. with raised left atrial pressure, pulmonary venous pressure and pulmonary capillary pressure.", "contents": "[Acute neurogenic pulmonary edema]. Neurogenic edema, in the strict sense of the term, has at the present time practically not benefitted from precise hemodynamic investigations in human clinical practice, and owing to this fact, authors still classify them under the heading \"mixed edema or of unknown pathogenesis\". In contrast with this lack of information in man, animal experimental works are surprising by their coherence and the experimental facility of producing neurogenic edema (cranial hypertension by a small inflatable balloon and cisternal infection of fibrin). If one excludes the now ancient vagal theories (CAMERON 1949; CAMPBELL, 1949) which were never confirmed, all of the most recent experimental works (SARNOFF, 1952; DUCKER, 1968; LUISADA, 1967; MORITZ, 1974) confirm the adrenergic disorder of central origin during neurogenic A.P.E. which from the hemodynamic standpoint is like an authentic hemodynamic A.P.E. with raised left atrial pressure, pulmonary venous pressure and pulmonary capillary pressure."}
{"id": "PMID:9873", "title": "[Pulmonary edema in hangings].", "content": "The authors present two cases of unsuccessful hanging which hat lead to a very severe neurological picture and especially the very rapid appearance of acute pulmonary edema resulting in a vertiable flooding of the alveoli. The victims, aged respectively 21 and 15 years, were free from any pre-existing cardiopathy. These cases of pulmonary edema, resistant to depletive therapy (bleeding, diuretics) and cardiotonic agents (Cedilanid) should only be jugulated after a one hour session of oxygen at 3 ATA with a baro-assisted respirator. The following are discussed with reference to these two cases: 1- The mode of occurrence of this type of pulmonary edema: - implication of sub-acute anoxic cerebral damage; - high negative alveolar pressures owing to a gasp-type ventilation with a closed glottis. 2- The opportunity for the very early treatment of the oxygen deficit contracted by the brain and myocardium.", "contents": "[Pulmonary edema in hangings]. The authors present two cases of unsuccessful hanging which hat lead to a very severe neurological picture and especially the very rapid appearance of acute pulmonary edema resulting in a vertiable flooding of the alveoli. The victims, aged respectively 21 and 15 years, were free from any pre-existing cardiopathy. These cases of pulmonary edema, resistant to depletive therapy (bleeding, diuretics) and cardiotonic agents (Cedilanid) should only be jugulated after a one hour session of oxygen at 3 ATA with a baro-assisted respirator. The following are discussed with reference to these two cases: 1- The mode of occurrence of this type of pulmonary edema: - implication of sub-acute anoxic cerebral damage; - high negative alveolar pressures owing to a gasp-type ventilation with a closed glottis. 2- The opportunity for the very early treatment of the oxygen deficit contracted by the brain and myocardium."}
{"id": "PMID:9874", "title": "[Nonhemodynamic pulmonary edema due to toxins].", "content": "Lesional pulmonary edema caused by substances which are directly caustic for the gastrointestinal pathways (strong acids and bases, inhaled vomit) are opposed by their immediate and long-term gravity with those due to cardiotropic medicamentatous toxins or volemic overloading which lead to curable pulmonary edema. Material and human factors, in favour of accidental intoxication are compensated for by the fact that many toxins produce vapours which are strongly irritant for the upper respiratory pathways: this prevents prolonged exposure and therefore wards off edema. Drug intoxication by ingestion can lead to pulmonary edema by relative or absolute volemic overload, by allergic accidents or by immaturity of the enzyme degradation systems. It seems to us that the notions of \"neurological\" and \"metabolic\" toxic edema should be abandoned. In lesional edema the treatment is that of the acute respiratory failure. The combination of pethidine, promethazine, and chlorpromazine gives good immediate results. Owing to careful follow-up, hemodynamic pulmonary edema should most frequently be avoided.", "contents": "[Nonhemodynamic pulmonary edema due to toxins]. Lesional pulmonary edema caused by substances which are directly caustic for the gastrointestinal pathways (strong acids and bases, inhaled vomit) are opposed by their immediate and long-term gravity with those due to cardiotropic medicamentatous toxins or volemic overloading which lead to curable pulmonary edema. Material and human factors, in favour of accidental intoxication are compensated for by the fact that many toxins produce vapours which are strongly irritant for the upper respiratory pathways: this prevents prolonged exposure and therefore wards off edema. Drug intoxication by ingestion can lead to pulmonary edema by relative or absolute volemic overload, by allergic accidents or by immaturity of the enzyme degradation systems. It seems to us that the notions of \"neurological\" and \"metabolic\" toxic edema should be abandoned. In lesional edema the treatment is that of the acute respiratory failure. The combination of pethidine, promethazine, and chlorpromazine gives good immediate results. Owing to careful follow-up, hemodynamic pulmonary edema should most frequently be avoided."}
{"id": "PMID:9875", "title": "[Pulmonary edemas due to acute heroin poisoning].", "content": "Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics.", "contents": "[Pulmonary edemas due to acute heroin poisoning]. Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics."}
{"id": "PMID:9876", "title": "[Oxygen toxicity for pulmonary parenchyma. Ultrastructural study by electron microscopy. Physiopathologic data].", "content": "The lungs of rats submitted to 24, 36, 48 and 72 hours of pure normobaric oxygen were examined by means of the scanning microscope. The images obtained give a dynamic aspect of the changes in the lesions with two distinct phases: a phase of reactivity at 48 hours, marked by the development of hyperactivity of the granular pneumocytes, a phase of destruction characterised by considerable changes in the alveolar epithelium and filling in of the alveolar lumen with various debris. From these morphological findings, different physio-pathological factors are discussed: the role of the increase in PaO2, the protection provided by the increase in the gradient (A - a) DO2, cerebral and adrenal medullary involvement especially in hypoxemic subjects.", "contents": "[Oxygen toxicity for pulmonary parenchyma. Ultrastructural study by electron microscopy. Physiopathologic data]. The lungs of rats submitted to 24, 36, 48 and 72 hours of pure normobaric oxygen were examined by means of the scanning microscope. The images obtained give a dynamic aspect of the changes in the lesions with two distinct phases: a phase of reactivity at 48 hours, marked by the development of hyperactivity of the granular pneumocytes, a phase of destruction characterised by considerable changes in the alveolar epithelium and filling in of the alveolar lumen with various debris. From these morphological findings, different physio-pathological factors are discussed: the role of the increase in PaO2, the protection provided by the increase in the gradient (A - a) DO2, cerebral and adrenal medullary involvement especially in hypoxemic subjects."}
{"id": "PMID:9877", "title": "[Pulmonary edema due to inhalation of gas and vapors].", "content": "In 1975, France will have manufactured 3.2 million tons of plastic materials which by pyrolysis, liberate chlorine, methyl chloride, hydrocyanic acid, hydrofluoric acid and other toxic gases. Now these materials are burnt in fires in \"modern\", buildings or vehicles , associated with fats (acrolein) and other gases and toxic industrial or household fumes which attack the lung. At sufficient dosage these agressive agents have first of all a \"suffocating\" action when in case of survival, a caustic and corrosive action. Pulmonary edema of the lesional type is met with at two stages in these cases. They are due to a direct action on the bronchial epithelium and an indirect action by disturbance of surfactant metabolism. It is an edema which is interstitial above all, and secondarily endo-alveolar. Study of the clinical, radiological, bronchoscopic and hemodynamic symptomatology. Differential diagnosis is not always easy. The possibility of burns of the respiratory pathways, blast, must be looked at. These elements can moreover be associated with lesions due to toxic inhalation. In case of survival the course is one of fibrosis with a restrictive syndrome.", "contents": "[Pulmonary edema due to inhalation of gas and vapors]. In 1975, France will have manufactured 3.2 million tons of plastic materials which by pyrolysis, liberate chlorine, methyl chloride, hydrocyanic acid, hydrofluoric acid and other toxic gases. Now these materials are burnt in fires in \"modern\", buildings or vehicles , associated with fats (acrolein) and other gases and toxic industrial or household fumes which attack the lung. At sufficient dosage these agressive agents have first of all a \"suffocating\" action when in case of survival, a caustic and corrosive action. Pulmonary edema of the lesional type is met with at two stages in these cases. They are due to a direct action on the bronchial epithelium and an indirect action by disturbance of surfactant metabolism. It is an edema which is interstitial above all, and secondarily endo-alveolar. Study of the clinical, radiological, bronchoscopic and hemodynamic symptomatology. Differential diagnosis is not always easy. The possibility of burns of the respiratory pathways, blast, must be looked at. These elements can moreover be associated with lesions due to toxic inhalation. In case of survival the course is one of fibrosis with a restrictive syndrome."}
{"id": "PMID:9878", "title": "[Classification of corticoids].", "content": "A pharmacological classification of corticoids can be carried out, based on the ratio of their glucocorticoid and mineralocorticoid activities. Their large number is due to the fact that they are practically all synthetic, and that minimal modifications in their structure gives rise to new drugs with variable gluco and mineralocorticoid activity.", "contents": "[Classification of corticoids]. A pharmacological classification of corticoids can be carried out, based on the ratio of their glucocorticoid and mineralocorticoid activities. Their large number is due to the fact that they are practically all synthetic, and that minimal modifications in their structure gives rise to new drugs with variable gluco and mineralocorticoid activity."}
{"id": "PMID:9879", "title": "[Glucocorticoids and metabolism].", "content": "After a brief historical account, the physiological effect of glucocorticoid hormones are analysed. Their main point of impact is neoglucogenesis from proteins. To this is added their direct action on carbohydrates, their intervention in the use of lipids, and in the movement of water and salts. Cortisone penetrates into the cell, is fixed by a cortisone receptor in order to be transferred into the nucleus and to act on the transformation of ADN-ARN. Its relationships with cyclic AMP are discussed. The hormonal correlations of glucocorticoids are numerous. (insulin, catecholamine, glucagon, growth hormone, androgen). Synthetic cordicoids have biological actions which are close to those of glucocorticoids, but vary depending on their structure. These physiological and pharmacological notions imply certain precautions in the use of this type of hormone derivative.", "contents": "[Glucocorticoids and metabolism]. After a brief historical account, the physiological effect of glucocorticoid hormones are analysed. Their main point of impact is neoglucogenesis from proteins. To this is added their direct action on carbohydrates, their intervention in the use of lipids, and in the movement of water and salts. Cortisone penetrates into the cell, is fixed by a cortisone receptor in order to be transferred into the nucleus and to act on the transformation of ADN-ARN. Its relationships with cyclic AMP are discussed. The hormonal correlations of glucocorticoids are numerous. (insulin, catecholamine, glucagon, growth hormone, androgen). Synthetic cordicoids have biological actions which are close to those of glucocorticoids, but vary depending on their structure. These physiological and pharmacological notions imply certain precautions in the use of this type of hormone derivative."}
{"id": "PMID:9880", "title": "[Study of carbohydrate tolerance without and with corticotherapy].", "content": "Using the glucose tolerance test by the intravenous route, from which the coefficients K (CONARD) of carbohydrate assimilation and (BERNIER) of fasting glycogenolysis, are deduced, the authors study the carbohydrate tolerance of neuro-surgical patients in acute and chronic phases, under corticosteroid therapy and without corticosteroid therapy. The role of corticosteroid therapy in the decrease in carbohydrate tolerance reported is discussed ; for comparative purposes, the authors present the study of carbohydrate assimilation in irreversible coma and in patients with advanced neuroplegia.", "contents": "[Study of carbohydrate tolerance without and with corticotherapy]. Using the glucose tolerance test by the intravenous route, from which the coefficients K (CONARD) of carbohydrate assimilation and (BERNIER) of fasting glycogenolysis, are deduced, the authors study the carbohydrate tolerance of neuro-surgical patients in acute and chronic phases, under corticosteroid therapy and without corticosteroid therapy. The role of corticosteroid therapy in the decrease in carbohydrate tolerance reported is discussed ; for comparative purposes, the authors present the study of carbohydrate assimilation in irreversible coma and in patients with advanced neuroplegia."}
{"id": "PMID:9881", "title": "[Corticoids in respiratory pathology].", "content": "After briefly recalling the action of corticosteroids on the normal and pathological lung, the authors review the different etiologies where they can be used in respiratory pathology.", "contents": "[Corticoids in respiratory pathology]. After briefly recalling the action of corticosteroids on the normal and pathological lung, the authors review the different etiologies where they can be used in respiratory pathology."}
{"id": "PMID:9882", "title": "[Immunological aspects of corticotherapy].", "content": "The therapeutic effectiveness of corticoids in transplantation, in autoimmune conditions and in numerous diseases in which the pathogenic role of hypersensitivity reactions is invoked, is perfectly established on the empirical basis of clinical cases. The study of the effects of corticoids on the immunological response is on the contrary very fragmentary; it comes up against numerous difficulties, especially against the differences in susceptibility from one species to another. The lymphoid cells have cytoplasmic and nuclear receptors for corticosteroids. The fixation of corticosteroids on lymphocytes inhibits the synthesis of nucleic acids and raises the intracellular level of cyclic AMP. Corticosteroids decrease the mobility of polymorph leukocytes in the presence of a chemotactic stimulus, at high doses, they disturb phagocytosis by marcophages, oppose the degranulation of mast cells and polymorph leukocytes, and the cytotoxic action of sensitised T lymphocytes. In vivo, corticosteroids have little effect on the production of antibodies (primary of secondary response) do not modify the \"immunological memory\" by through an anti-inflammatory effect, abolish the peripheral manifestations of late hypersentsitivity reactions. Corticosteroids enable the treatment of acute rejection crises in transplantation, they have a symptomatic effect on type I and IV Gel and Cooms hypersensitivity reaction, their activity is less regular in the other phenomena of hypersensitivity.", "contents": "[Immunological aspects of corticotherapy]. The therapeutic effectiveness of corticoids in transplantation, in autoimmune conditions and in numerous diseases in which the pathogenic role of hypersensitivity reactions is invoked, is perfectly established on the empirical basis of clinical cases. The study of the effects of corticoids on the immunological response is on the contrary very fragmentary; it comes up against numerous difficulties, especially against the differences in susceptibility from one species to another. The lymphoid cells have cytoplasmic and nuclear receptors for corticosteroids. The fixation of corticosteroids on lymphocytes inhibits the synthesis of nucleic acids and raises the intracellular level of cyclic AMP. Corticosteroids decrease the mobility of polymorph leukocytes in the presence of a chemotactic stimulus, at high doses, they disturb phagocytosis by marcophages, oppose the degranulation of mast cells and polymorph leukocytes, and the cytotoxic action of sensitised T lymphocytes. In vivo, corticosteroids have little effect on the production of antibodies (primary of secondary response) do not modify the \"immunological memory\" by through an anti-inflammatory effect, abolish the peripheral manifestations of late hypersentsitivity reactions. Corticosteroids enable the treatment of acute rejection crises in transplantation, they have a symptomatic effect on type I and IV Gel and Cooms hypersensitivity reaction, their activity is less regular in the other phenomena of hypersensitivity."}
{"id": "PMID:9883", "title": "[Hemodynamic effects of high-dosage corticoids. Their justification in the treatment of shock].", "content": "In 61 patients in whom high doses of corticoids had been administered owing to various indications, the hemodynamic modifications caused by this injection were studied. The corticoids administered were : hydrocortisone hemisucccinate (150 mg/kg), methyl prednisolone sulfate (30 mg/kg), prednisone sodium m sulfobenzoate (50 mg/kg), prednisolone sodium m sulfobenzoate (35 mg/kg) and dexamethasone phosphate (2 mg and 6 mg/kg). The results study the modifications caused by each drug on heart rate, arterial blood pressure, cardiac output, systolic stroke volume and peripheral vascular resistance. The expression of the results is given as a percentage of the variation with statistical study. Methyl-prednisolone sulfobenzoate only leads to slightly marked hemodynamic effects : the four other compounds studied have definite hemodynamic effects, of variable intensity and duration. The most important variations are noted with dexametasone phosphate. From these results, the indications and results of the use of corticoids in states of shock are discussed.", "contents": "[Hemodynamic effects of high-dosage corticoids. Their justification in the treatment of shock]. In 61 patients in whom high doses of corticoids had been administered owing to various indications, the hemodynamic modifications caused by this injection were studied. The corticoids administered were : hydrocortisone hemisucccinate (150 mg/kg), methyl prednisolone sulfate (30 mg/kg), prednisone sodium m sulfobenzoate (50 mg/kg), prednisolone sodium m sulfobenzoate (35 mg/kg) and dexamethasone phosphate (2 mg and 6 mg/kg). The results study the modifications caused by each drug on heart rate, arterial blood pressure, cardiac output, systolic stroke volume and peripheral vascular resistance. The expression of the results is given as a percentage of the variation with statistical study. Methyl-prednisolone sulfobenzoate only leads to slightly marked hemodynamic effects : the four other compounds studied have definite hemodynamic effects, of variable intensity and duration. The most important variations are noted with dexametasone phosphate. From these results, the indications and results of the use of corticoids in states of shock are discussed."}
{"id": "PMID:9884", "title": "[Corticoids and shock].", "content": "After recalling the major role of catecholamines in the genesis of irreversible shock, the anti-shock action of glucocorticosteroids, owing to properties which are \"alpha-blocking\" , is discussed in this work. The works of LILLEHEI on the effectiveness of corticosteroids in different types of shock are summarized and discussed, as well as numerous works which have followed and a synopsis of which, done in 1967 in the \"Annales de l'Anesth\u00e9siologie Francaise\", is presented. Since then, following new experimental facts, whereas numerous contradictions have appeared in the clinical and experimental realms, the possible mechanisms of action of corticosteroids in shock are looked at, by emphasizing the relationships between corticosteroids and SHWARTZMAN's phenomenon, in particular. A hypothesis on a probable central action of glucocorticosteroids is proposed following experimental works carried out by H. LABORIT et Coll. (1975). Finally, the author presents a personal experiment in hemorrhagic shock in the rabbit where the adjunction of corticosteroids had no effect on the different parameters such as the decrease in PaCO2, hyperlactacidemia and the liberation of beta-glycuronidase in the blood, mortality being practically the same in the controls and in the animals submitted to corticosteroid therapy.", "contents": "[Corticoids and shock]. After recalling the major role of catecholamines in the genesis of irreversible shock, the anti-shock action of glucocorticosteroids, owing to properties which are \"alpha-blocking\" , is discussed in this work. The works of LILLEHEI on the effectiveness of corticosteroids in different types of shock are summarized and discussed, as well as numerous works which have followed and a synopsis of which, done in 1967 in the \"Annales de l'Anesth\u00e9siologie Francaise\", is presented. Since then, following new experimental facts, whereas numerous contradictions have appeared in the clinical and experimental realms, the possible mechanisms of action of corticosteroids in shock are looked at, by emphasizing the relationships between corticosteroids and SHWARTZMAN's phenomenon, in particular. A hypothesis on a probable central action of glucocorticosteroids is proposed following experimental works carried out by H. LABORIT et Coll. (1975). Finally, the author presents a personal experiment in hemorrhagic shock in the rabbit where the adjunction of corticosteroids had no effect on the different parameters such as the decrease in PaCO2, hyperlactacidemia and the liberation of beta-glycuronidase in the blood, mortality being practically the same in the controls and in the animals submitted to corticosteroid therapy."}
{"id": "PMID:9885", "title": "[Corticosteroids and septic shock].", "content": "According to the data in the literature, the authors attempted to sum-up present attitudes on the value of corticoids in the treatment of septic shock. If their cardiovascular effects after a period of enthusiasm, are presently rather controversial, their cellular and sub-cellular actions, on the lysosomal membranes, capillary permeability and perhaps the intimate mechanisms of cellular oxygenation seem to be more real. However, the contra-indications which persist in the results of clinical works have resulted in the fact that the exact place of cortico-steroids in the therapeutic arsenal of septic shock still remains to be specified.", "contents": "[Corticosteroids and septic shock]. According to the data in the literature, the authors attempted to sum-up present attitudes on the value of corticoids in the treatment of septic shock. If their cardiovascular effects after a period of enthusiasm, are presently rather controversial, their cellular and sub-cellular actions, on the lysosomal membranes, capillary permeability and perhaps the intimate mechanisms of cellular oxygenation seem to be more real. However, the contra-indications which persist in the results of clinical works have resulted in the fact that the exact place of cortico-steroids in the therapeutic arsenal of septic shock still remains to be specified."}
{"id": "PMID:9886", "title": "[Plasma cortisol in neurosurgical resuscitation].", "content": "The authors study the values of spontaneous cortisonemia in neuro-surgical patients. They analysed the correlations between this parameter and certain clinical criteria (age, etiology, level of consciousness), the duration and nyctohemeral changes in spontaneous hypercortisonism. Furthermore, they presented the values of iatrogenic cortisonemias as a function of increasing doses of hydrocortisone and discussed the possible mechanisms for the disapperance of injected cortisone.", "contents": "[Plasma cortisol in neurosurgical resuscitation]. The authors study the values of spontaneous cortisonemia in neuro-surgical patients. They analysed the correlations between this parameter and certain clinical criteria (age, etiology, level of consciousness), the duration and nyctohemeral changes in spontaneous hypercortisonism. Furthermore, they presented the values of iatrogenic cortisonemias as a function of increasing doses of hydrocortisone and discussed the possible mechanisms for the disapperance of injected cortisone."}
{"id": "PMID:9887", "title": "[Indications for anti-inflammatory corticoids in anesthesia-resuscitiation].", "content": "The use of anti-inflammatory corticoids in anesthesia and resuscitation is a long-standing fact, but their indications, owing to the risks to which they expose certain patients and owing to the uncertitude concerning their mechanism of action, are still badly defined. If certain indications (attacks of asthma, laryngeal oedema, certain peri-lesional oedemas) are considered as being categorial, the usefulness of anti-inflammatory corticotherapy is being more and more and more debated in other pathological conditions : infectious or chemical pneumonias, drowning, shocked lung, post-traumatic neuro-surgical conditions, cirrhosis. Very useful in precise indications, anti-inflammatory corticoids should not be prescribed, particularly in fragile patients whom we well know in resuscitation, without having weighed up the advantages and disadvantages related to this remarkable therapeutic instrument.", "contents": "[Indications for anti-inflammatory corticoids in anesthesia-resuscitiation]. The use of anti-inflammatory corticoids in anesthesia and resuscitation is a long-standing fact, but their indications, owing to the risks to which they expose certain patients and owing to the uncertitude concerning their mechanism of action, are still badly defined. If certain indications (attacks of asthma, laryngeal oedema, certain peri-lesional oedemas) are considered as being categorial, the usefulness of anti-inflammatory corticotherapy is being more and more and more debated in other pathological conditions : infectious or chemical pneumonias, drowning, shocked lung, post-traumatic neuro-surgical conditions, cirrhosis. Very useful in precise indications, anti-inflammatory corticoids should not be prescribed, particularly in fragile patients whom we well know in resuscitation, without having weighed up the advantages and disadvantages related to this remarkable therapeutic instrument."}
{"id": "PMID:9888", "title": "[Complications and contraindications of corticotherapy].", "content": "In a review of the classical complications of corticotherapy the aouthors tried, in the light of the literature, to take into consideration the ideas received as compared with the numerical conclusions of statistical studies on large series. Then they presented the patient treated with corticoids, faced with the surgical intervention. They tried to demonstrate that adrenal insufficiency, if present, is only exceptional and that all of the incidents, observed during and immediately after surgery must not be attributed to it.", "contents": "[Complications and contraindications of corticotherapy]. In a review of the classical complications of corticotherapy the aouthors tried, in the light of the literature, to take into consideration the ideas received as compared with the numerical conclusions of statistical studies on large series. Then they presented the patient treated with corticoids, faced with the surgical intervention. They tried to demonstrate that adrenal insufficiency, if present, is only exceptional and that all of the incidents, observed during and immediately after surgery must not be attributed to it."}
{"id": "PMID:9889", "title": "[Problems posed by surgical patients submitted to long-term corticotherapy].", "content": "Contrary to the long-standing attitude which consisted of descreasing the doses of cortisone, or even of weaning patients before undergoing a surgical intervention, the author emphasizes the necessity for a quantitative and qualitative increase in corticotherapy in order to avoid the risks of acute hypocorti-costeroidism.", "contents": "[Problems posed by surgical patients submitted to long-term corticotherapy]. Contrary to the long-standing attitude which consisted of descreasing the doses of cortisone, or even of weaning patients before undergoing a surgical intervention, the author emphasizes the necessity for a quantitative and qualitative increase in corticotherapy in order to avoid the risks of acute hypocorti-costeroidism."}
{"id": "PMID:9890", "title": "[Determination of phenobarbital, mephenytoin and diphenylhydantoin in the surveillance of anticonvulsant treatment].", "content": "The authors describe a method of simultaneous estimation of phenobarbitone, mephenytoin and diphenylhydantoin in the blood. After extraction with ether, the methylation of these substances by trimethylanilinium hydroxide permits their rapid separation by gas chromatography. Heptabarbitone is used as internal standard and the chromatograph used is supplied with a thermoionic detector. The technique used is simple and rapid. Its reproducibility and sensitivity are satisfactory, permitting daily application to the supervision of anticonvulsant treatment, especially in Pediatrics.", "contents": "[Determination of phenobarbital, mephenytoin and diphenylhydantoin in the surveillance of anticonvulsant treatment]. The authors describe a method of simultaneous estimation of phenobarbitone, mephenytoin and diphenylhydantoin in the blood. After extraction with ether, the methylation of these substances by trimethylanilinium hydroxide permits their rapid separation by gas chromatography. Heptabarbitone is used as internal standard and the chromatograph used is supplied with a thermoionic detector. The technique used is simple and rapid. Its reproducibility and sensitivity are satisfactory, permitting daily application to the supervision of anticonvulsant treatment, especially in Pediatrics."}
{"id": "PMID:9891", "title": "[Determination of isoniazid in blood plasma].", "content": "The authors describe a new method of estimation of isoniazid in biological fluids, based on the formation and extraction of aluminium chelate obtained after combination of the isoniazid with salicylic aldehyde. The study of conditions of defecation and reaction permits one to eliminate interference with the metabolites, especially the acido-labile metabolites and obtain results comparable with those of microbiological methods.", "contents": "[Determination of isoniazid in blood plasma]. The authors describe a new method of estimation of isoniazid in biological fluids, based on the formation and extraction of aluminium chelate obtained after combination of the isoniazid with salicylic aldehyde. The study of conditions of defecation and reaction permits one to eliminate interference with the metabolites, especially the acido-labile metabolites and obtain results comparable with those of microbiological methods."}
{"id": "PMID:9893", "title": "[Electrogastroenterographic study of the digestive motor effects of prolonged psychotropic treatment].", "content": "Functional digestive complaints are frequent in psychiatri patients: simple constipation, which cannot be explained solely by the loss of the sensation of rectal fullness; occlusions, occasionally hemorragies; the late complication of dolichomegacolon (Bourgeois, 1973). In 160 subjects, an attempt to understand the physio-pathology were made by recording diurnal digestive motor activity using skin electrodes placed on the abdomen and extremities (electrogastroenterography or E.G.E.G.). A hypoactive E.G.E.G. was observed in 2/3 of 18 psychotic depressive patients, in 3/4 of 36 schizophrenies. The nocive effect of giving sedative phenothiazine and antiparkinsonian drugs (trihexyphenidyl or ethybenzatropine) during long periods is clear. Whereas non sedative phenothiazine and clotiapine gicen in small doses, do not have an undesirable effect. Sulpiride has been used in gastroduodenal dyskinesia. The dyskinesia noted by the E.G.E.G., sometimes found in the large intestin, were found in 55% of 30 patients with caracter disorders; they coincide with the high frequency of electro-encephalogram dysrythmies. Finally, in hysterical patients, one usually observes normal E.G.E.G., tracings which confirms the clinical observation that hysterical and psychosomatic symptoms, may succeed each other, but do not appear at the same time. In the same categories of patients, no longer treated in a classical psychiatric environment but in a group with institutional objectives, the same clinic results were obtained with fewer digestive disturbances. This tends to show the inutility and nocivity of excessive doses of psychotropic drugs given alone or in complexe association.", "contents": "[Electrogastroenterographic study of the digestive motor effects of prolonged psychotropic treatment]. Functional digestive complaints are frequent in psychiatri patients: simple constipation, which cannot be explained solely by the loss of the sensation of rectal fullness; occlusions, occasionally hemorragies; the late complication of dolichomegacolon (Bourgeois, 1973). In 160 subjects, an attempt to understand the physio-pathology were made by recording diurnal digestive motor activity using skin electrodes placed on the abdomen and extremities (electrogastroenterography or E.G.E.G.). A hypoactive E.G.E.G. was observed in 2/3 of 18 psychotic depressive patients, in 3/4 of 36 schizophrenies. The nocive effect of giving sedative phenothiazine and antiparkinsonian drugs (trihexyphenidyl or ethybenzatropine) during long periods is clear. Whereas non sedative phenothiazine and clotiapine gicen in small doses, do not have an undesirable effect. Sulpiride has been used in gastroduodenal dyskinesia. The dyskinesia noted by the E.G.E.G., sometimes found in the large intestin, were found in 55% of 30 patients with caracter disorders; they coincide with the high frequency of electro-encephalogram dysrythmies. Finally, in hysterical patients, one usually observes normal E.G.E.G., tracings which confirms the clinical observation that hysterical and psychosomatic symptoms, may succeed each other, but do not appear at the same time. In the same categories of patients, no longer treated in a classical psychiatric environment but in a group with institutional objectives, the same clinic results were obtained with fewer digestive disturbances. This tends to show the inutility and nocivity of excessive doses of psychotropic drugs given alone or in complexe association."}
{"id": "PMID:9898", "title": "Effect of acid and salt concentration in fresh-pack pickles on the growth of Clostridium botulinum spores.", "content": "The addition of various amounts of acetic acid to pureed cucumbers inoculated with Clostridium botulinum spores has shown that outgrowth is inhibited at pH 4.8 but not at pH 5.0. Inoculation experiments with whole cucumbers showed that as little as 0.9% acetic acid in the brine was sufficient to prevent outgrowth from spore inocula as high as 10(6)/cucumber. It was further shown that the rapid rate of acetic acid penetration into fresh-pack pickles prevents the growth of any C. botulinum spores that may be present.", "contents": "Effect of acid and salt concentration in fresh-pack pickles on the growth of Clostridium botulinum spores. The addition of various amounts of acetic acid to pureed cucumbers inoculated with Clostridium botulinum spores has shown that outgrowth is inhibited at pH 4.8 but not at pH 5.0. Inoculation experiments with whole cucumbers showed that as little as 0.9% acetic acid in the brine was sufficient to prevent outgrowth from spore inocula as high as 10(6)/cucumber. It was further shown that the rapid rate of acetic acid penetration into fresh-pack pickles prevents the growth of any C. botulinum spores that may be present."}
{"id": "PMID:9896", "title": "[On the ecology of marine chromatiaceae and chlorobiaceae (author's transl)].", "content": "Number and genera (types) of phototrophic red and green sulfur bacteria have been determined in the upper layer of eleven marine sediment samples from the euphotic zone in the Mediterranean Sea. Origin and nature of the sediment samples are given as well as their pH, total nitrogen and sulfide content. The results show that the sediments studied did not provide good growth conditions for Chromatiaceae (Chromatium, Thiocystis, Thiocapsa) and Chlorobiaceae (Prosthecochloris). The total number of these bacteria varied in agreement with the total nitrogen content (organic matter) of the samples; the organic matter content is, therefore, of primary importance for the occurrence of the red and green sulfur bacteria in the samples.", "contents": "[On the ecology of marine chromatiaceae and chlorobiaceae (author's transl)]. Number and genera (types) of phototrophic red and green sulfur bacteria have been determined in the upper layer of eleven marine sediment samples from the euphotic zone in the Mediterranean Sea. Origin and nature of the sediment samples are given as well as their pH, total nitrogen and sulfide content. The results show that the sediments studied did not provide good growth conditions for Chromatiaceae (Chromatium, Thiocystis, Thiocapsa) and Chlorobiaceae (Prosthecochloris). The total number of these bacteria varied in agreement with the total nitrogen content (organic matter) of the samples; the organic matter content is, therefore, of primary importance for the occurrence of the red and green sulfur bacteria in the samples."}
{"id": "PMID:9899", "title": "Isolation and characterization of an enzyme with esterase activity from Micropolyspora faeni.", "content": "The isolation and the characterization of one of the enzymes of Micropolyspora faeni that hydrolyzes the substrate N-benzoyl-DL-phenylalanine-beta-naphthyl ester and that seems to be of medical importance are described. This enzyme (enzyme 1) was isolated with an 86-fold purification by using the following seven steps: ammonium sulfate precipitation, gel filtration through Sephadex G-150, heat treatment, chromatography on diethylaminoethyl-cellulose, rechromatography on diethylaminoethyl-Sephadex, gel filtration through Sephadex G-200, and affinity chromatography. Enzyme 1 has a molecular weight of approximately 500,000 and maximum activity at pH 7.8 to 8.0 and at 20 degrees C. The enzyme is stable between pH 7.5 and 10.5 and at temperatures up to 60 degrees C. Its activity is not inhibited by ethylenediaminetetraacetic acid. It is, however, sensitive to diisopropyl phosphofluoride and phenylmethyl sulfonyl fluoride. These properties and the ability to hydrolyze the esters of phenylalanine, tyrosine, and tryptophan without endopeptidasic activity and no marked proteolytic activity suggest that the enzyme is an esterase.", "contents": "Isolation and characterization of an enzyme with esterase activity from Micropolyspora faeni. The isolation and the characterization of one of the enzymes of Micropolyspora faeni that hydrolyzes the substrate N-benzoyl-DL-phenylalanine-beta-naphthyl ester and that seems to be of medical importance are described. This enzyme (enzyme 1) was isolated with an 86-fold purification by using the following seven steps: ammonium sulfate precipitation, gel filtration through Sephadex G-150, heat treatment, chromatography on diethylaminoethyl-cellulose, rechromatography on diethylaminoethyl-Sephadex, gel filtration through Sephadex G-200, and affinity chromatography. Enzyme 1 has a molecular weight of approximately 500,000 and maximum activity at pH 7.8 to 8.0 and at 20 degrees C. The enzyme is stable between pH 7.5 and 10.5 and at temperatures up to 60 degrees C. Its activity is not inhibited by ethylenediaminetetraacetic acid. It is, however, sensitive to diisopropyl phosphofluoride and phenylmethyl sulfonyl fluoride. These properties and the ability to hydrolyze the esters of phenylalanine, tyrosine, and tryptophan without endopeptidasic activity and no marked proteolytic activity suggest that the enzyme is an esterase."}
{"id": "PMID:9897", "title": "Therapeutic drug monitoring: measurements of antiepileptic and barbiturate drug levels in blood by gas chromatography with nitrogen - selective detector.", "content": "The nitrogen-specific detector for gas chromatography consists of a non-volatile rubidium silicate bead, around which nitrogen-containing compounds are pyrolyzed. Speed, sensitivity, specificity, accuracy, small sample size and minumum sample handling are characteristics of the nitrogen detector that render it superior to conventional gas chromatographic detectors. The detector has been utilized to effect a simple and rapid quantitation of allobarbital, amobarbital, butabarbital, heptabarbital, pentabarbital, phenobarbital and secobarbital, plus the anticonvulsants diphenylhydantoin and primidone. Extraction of the drugs from acidified serum into organic solvent containing internal standard is followed by oncolumn methylation with methanolic trimethylphenyl ammonium hydroxide. The drugs, separated on a column of 3 percent OV-101 on Gas-Chrom Q, 100-120 mesh are readily quantitated by simple calculations based on peak-height ratios. Therapeutic drug monitoring is discussed in relation to recent concepts of drug-protein binding, drug-drug interactions, drug biotransformation and problems of multiple drug therapy.", "contents": "Therapeutic drug monitoring: measurements of antiepileptic and barbiturate drug levels in blood by gas chromatography with nitrogen - selective detector. The nitrogen-specific detector for gas chromatography consists of a non-volatile rubidium silicate bead, around which nitrogen-containing compounds are pyrolyzed. Speed, sensitivity, specificity, accuracy, small sample size and minumum sample handling are characteristics of the nitrogen detector that render it superior to conventional gas chromatographic detectors. The detector has been utilized to effect a simple and rapid quantitation of allobarbital, amobarbital, butabarbital, heptabarbital, pentabarbital, phenobarbital and secobarbital, plus the anticonvulsants diphenylhydantoin and primidone. Extraction of the drugs from acidified serum into organic solvent containing internal standard is followed by oncolumn methylation with methanolic trimethylphenyl ammonium hydroxide. The drugs, separated on a column of 3 percent OV-101 on Gas-Chrom Q, 100-120 mesh are readily quantitated by simple calculations based on peak-height ratios. Therapeutic drug monitoring is discussed in relation to recent concepts of drug-protein binding, drug-drug interactions, drug biotransformation and problems of multiple drug therapy."}
{"id": "PMID:9900", "title": "Oxidation of ethane by an Acremonium species.", "content": "Ethane oxidation was studied in ethane-grown resting cells (mycelia) of an Acremonium sp. and in cell-free preparations of such mycelia. From resting cell experiments evidence was found for a pathway of ethane oxidation via ethanol, acetaldehyde, and acetic acid. In vitro studies indicated that ethane-oxidizing activity in such mycelia occurred predominantly in the microsomal fraction of crude homogenates. Microsomal preparations were inactive in the absence of added coenzyme. Marked stimulation of activity was obtained in such preparations with reduced nicotinamide adenine dinucleotide phosphate and to a much lesser degree with nicotinamide adenine dinucleotide phosphate. Ethane oxidation was inhibited by sodium azide and carbon monoxide.", "contents": "Oxidation of ethane by an Acremonium species. Ethane oxidation was studied in ethane-grown resting cells (mycelia) of an Acremonium sp. and in cell-free preparations of such mycelia. From resting cell experiments evidence was found for a pathway of ethane oxidation via ethanol, acetaldehyde, and acetic acid. In vitro studies indicated that ethane-oxidizing activity in such mycelia occurred predominantly in the microsomal fraction of crude homogenates. Microsomal preparations were inactive in the absence of added coenzyme. Marked stimulation of activity was obtained in such preparations with reduced nicotinamide adenine dinucleotide phosphate and to a much lesser degree with nicotinamide adenine dinucleotide phosphate. Ethane oxidation was inhibited by sodium azide and carbon monoxide."}
{"id": "PMID:9901", "title": "Enzymatic hydrolysis of organophosphate insecticides, a possible pesticide disposal method.", "content": "A crude cell extract from a mixed bacterial culture growing on parathion, an organophosphate insecticide, hydrolyzed parathion (21 C) at a rate of 416 nmol/min per mg of protein. This rate of enzymatic hydrolysis, when compared with chemical hydrolysis by 0.1 N sodium hydroxide at 40 C, was 2, 450 times faster. Eight of 12 commonly used organophosphate insecticides were enzymatically hydrolyzed with this enzyme preparation at rates ranging from 12 to 1,360 nmol/min per mg of protein. Seven pesticides were hydrolyzed at rates significantly higher (40 to 1,005 times faster) than chemical hydrolysis. The pH optimum for enzymatic hydrolysis of the eight pesticides ranged from 8.5 to 9.5, with less than 50% of maximal activity expressed at pH 7.0. Maximal enzyme activity occurred at 35 C. The crude extract lost its activity at the rate of only 0.75%/day when stored at 6 C. Eight organic solvents, ranging from methanol to hexane, at low concentrations stimulated enzymatic hydrolysis by 3 to 20%, whereas at higher concentrations (1,000 mg/liter) they inhibited the reaction (9 to 50%). Parathion metabolites p-nitrophenol, hydroquinone, and diethylthiophosphoric acid, at up to 100-mg/liter concentrations, did not significantly influence enzyme activity.", "contents": "Enzymatic hydrolysis of organophosphate insecticides, a possible pesticide disposal method. A crude cell extract from a mixed bacterial culture growing on parathion, an organophosphate insecticide, hydrolyzed parathion (21 C) at a rate of 416 nmol/min per mg of protein. This rate of enzymatic hydrolysis, when compared with chemical hydrolysis by 0.1 N sodium hydroxide at 40 C, was 2, 450 times faster. Eight of 12 commonly used organophosphate insecticides were enzymatically hydrolyzed with this enzyme preparation at rates ranging from 12 to 1,360 nmol/min per mg of protein. Seven pesticides were hydrolyzed at rates significantly higher (40 to 1,005 times faster) than chemical hydrolysis. The pH optimum for enzymatic hydrolysis of the eight pesticides ranged from 8.5 to 9.5, with less than 50% of maximal activity expressed at pH 7.0. Maximal enzyme activity occurred at 35 C. The crude extract lost its activity at the rate of only 0.75%/day when stored at 6 C. Eight organic solvents, ranging from methanol to hexane, at low concentrations stimulated enzymatic hydrolysis by 3 to 20%, whereas at higher concentrations (1,000 mg/liter) they inhibited the reaction (9 to 50%). Parathion metabolites p-nitrophenol, hydroquinone, and diethylthiophosphoric acid, at up to 100-mg/liter concentrations, did not significantly influence enzyme activity."}
{"id": "PMID:9902", "title": "Effects of added germination agents on loss of optical density in electron-irradiated spores.", "content": "Spores of Bacillus megaterium ATCC 14581, subjected to partial-cell iradiation, were exposed to either lysozyme, H2O2, or glucose in an attempt to reduce or eliminate the nonmonotonic behavior in curves of percentage of germination versus energy, obtained when such spores were resuspended in phosphate buffer alone. Except at the lower doses. H2O2 effectively eliminated this anomalous dip in these curves, whereas lysozyme amplified it greatly. Glucose was generally ineffective. Coinciding with the increases in optical density when lysozyme was present was the formation of an occluding product.", "contents": "Effects of added germination agents on loss of optical density in electron-irradiated spores. Spores of Bacillus megaterium ATCC 14581, subjected to partial-cell iradiation, were exposed to either lysozyme, H2O2, or glucose in an attempt to reduce or eliminate the nonmonotonic behavior in curves of percentage of germination versus energy, obtained when such spores were resuspended in phosphate buffer alone. Except at the lower doses. H2O2 effectively eliminated this anomalous dip in these curves, whereas lysozyme amplified it greatly. Glucose was generally ineffective. Coinciding with the increases in optical density when lysozyme was present was the formation of an occluding product."}
{"id": "PMID:9913", "title": "The accumulation and loss of dieldrin and endrin in the eastern oyster.", "content": "Oysters demonstrated an ability to significantly concentrate dieldrin and endrin. Concentration ratios obtained after 168-hr exposures to endrin were 1670 at 0.1 mug/L and 2780 at 50 mug/L. Dieldrin was concentrated to higher levels. Exposure to 14C-labelled dieldrin at 0.5 mug/L produced whole body concentrations 2880 times the ambient level at 168 hr, while exposure to nine mug/L of dieldrin resulted in a concentration ratio of 2070 following the same period of exposure. Both endrin and dieldrin showed distinct linear regions in semi-logarithmic plots of uptake against time. Initial uptake was rapid and was followed by somewhat slower but still rapid uptake over the next 6 to 48 hr. Uptake within each of the stages followed an exponential form.", "contents": "The accumulation and loss of dieldrin and endrin in the eastern oyster. Oysters demonstrated an ability to significantly concentrate dieldrin and endrin. Concentration ratios obtained after 168-hr exposures to endrin were 1670 at 0.1 mug/L and 2780 at 50 mug/L. Dieldrin was concentrated to higher levels. Exposure to 14C-labelled dieldrin at 0.5 mug/L produced whole body concentrations 2880 times the ambient level at 168 hr, while exposure to nine mug/L of dieldrin resulted in a concentration ratio of 2070 following the same period of exposure. Both endrin and dieldrin showed distinct linear regions in semi-logarithmic plots of uptake against time. Initial uptake was rapid and was followed by somewhat slower but still rapid uptake over the next 6 to 48 hr. Uptake within each of the stages followed an exponential form."}
{"id": "PMID:9914", "title": "Fundoplication for reflux esophagitis: misadventures with the operation of choice.", "content": "Fundoplication, whether performed by thoracic or abdominal approach, is a sound method for control of reflux esophagitis. A series of 312 operations have been reviewed to assess the frequency of complications and the methods by which these can be prevented or treated effectively. Each source of an untoward outcome is examined in detail, and suggestions as to prevention or recognition are advanced. The current low death and complication rates have been lowered even more by a conscious effort to refine the procedure further; such efforts have been associated with a failure rate of less than 5% in a mean followup of 4 years.", "contents": "Fundoplication for reflux esophagitis: misadventures with the operation of choice. Fundoplication, whether performed by thoracic or abdominal approach, is a sound method for control of reflux esophagitis. A series of 312 operations have been reviewed to assess the frequency of complications and the methods by which these can be prevented or treated effectively. Each source of an untoward outcome is examined in detail, and suggestions as to prevention or recognition are advanced. The current low death and complication rates have been lowered even more by a conscious effort to refine the procedure further; such efforts have been associated with a failure rate of less than 5% in a mean followup of 4 years."}
{"id": "PMID:9916", "title": "Gastroesophageal reflux in esophageal scleroderma: diagnosis and implications.", "content": "Fifty-three patients with scleroderma were evaluated by history, barium swallow, and esophageal function tests. The most common esophageal symptoms were heartburn and dysphagia. Abnormal motility was seen radiologically in 43 patients, gastroesophageal reflux in only 9. Esophageal function tests demonstrated: (1) abnormal motility in 51 patients and lack of a distal esophageal high-pressure zone in 18; (2) moderate to severe gastroesophageal reflux in 38; and (3) abnormal acid-clearing ability in 50. Eleven patients, including 8 with peptic stricture, underwent the combined Collis-Belsey operation. Symptomatically, reflux was abolished in all and dysphagia in 10. Roentgenograms showed that regression of strictures was complete in 5 and partial in 3. Postoperative esophageal function tests in 9 patients demonstrated a competent distal esophageal valvular mechanism in 7. Gastroesophageal reflux, not impaired motility, is the major cause of esophageal symptoms in scleroderma. Its effecitve operative control is not contraindicated by systemic disease in these patients.", "contents": "Gastroesophageal reflux in esophageal scleroderma: diagnosis and implications. Fifty-three patients with scleroderma were evaluated by history, barium swallow, and esophageal function tests. The most common esophageal symptoms were heartburn and dysphagia. Abnormal motility was seen radiologically in 43 patients, gastroesophageal reflux in only 9. Esophageal function tests demonstrated: (1) abnormal motility in 51 patients and lack of a distal esophageal high-pressure zone in 18; (2) moderate to severe gastroesophageal reflux in 38; and (3) abnormal acid-clearing ability in 50. Eleven patients, including 8 with peptic stricture, underwent the combined Collis-Belsey operation. Symptomatically, reflux was abolished in all and dysphagia in 10. Roentgenograms showed that regression of strictures was complete in 5 and partial in 3. Postoperative esophageal function tests in 9 patients demonstrated a competent distal esophageal valvular mechanism in 7. Gastroesophageal reflux, not impaired motility, is the major cause of esophageal symptoms in scleroderma. Its effecitve operative control is not contraindicated by systemic disease in these patients."}
{"id": "PMID:9917", "title": "Giant cell arteritis with visceral angiitis.", "content": "We describe a case in which giant cell arteritis coexisted with microscopic polyarteritis nodosa and focal-local glomerulonephritis. We also review previous cases of renal abnormalities in giant cell arteritis. We believe that this association of inflammatory renal disease and giant cell arteritis has not been documented in the past.", "contents": "Giant cell arteritis with visceral angiitis. We describe a case in which giant cell arteritis coexisted with microscopic polyarteritis nodosa and focal-local glomerulonephritis. We also review previous cases of renal abnormalities in giant cell arteritis. We believe that this association of inflammatory renal disease and giant cell arteritis has not been documented in the past."}
{"id": "PMID:9918", "title": "[Experimental electric and biochemical data on ventricular fibrillation due to ischemia].", "content": "The author presents the results of prolonged research into ventricular fibrillation during myocardial ischaemia, both from the electrocardiographic and biochemical standpoints. - He emphasises the successive tonic and atonic features of VF due to ischaemia, and the difference between the fibrillation in an ischaemic area and in a control area. The most original concept is that there is often a difference between the onset of VF in an ischaemic zone and in a control zone. This study has been carried out with both acute and progressive ischaemia. - The biochemical studies were carried out on blood samples taken from the origin of the coronary arteries, the coronary veins, and from the saphenous veins. An important finding was the definite increase in the potassium level of the coronary venous blood in proportion to the degree of ischaemia; the sodium level showed little change, and if anything tended to fall. But the most important and distinctive finding was that at the onset of VF the sodium and potassium concentrations in the coronary venous blood suddenly increase. As the VF continues, there is a progressive increase in lactic acid and a fall in pH, which is maximal at the onset of the VF. These findings are valid under normothermic conditions, and when there is no extracorporeal circulation. - The physiopathological and practical implications of these facts are discussed.", "contents": "[Experimental electric and biochemical data on ventricular fibrillation due to ischemia]. The author presents the results of prolonged research into ventricular fibrillation during myocardial ischaemia, both from the electrocardiographic and biochemical standpoints. - He emphasises the successive tonic and atonic features of VF due to ischaemia, and the difference between the fibrillation in an ischaemic area and in a control area. The most original concept is that there is often a difference between the onset of VF in an ischaemic zone and in a control zone. This study has been carried out with both acute and progressive ischaemia. - The biochemical studies were carried out on blood samples taken from the origin of the coronary arteries, the coronary veins, and from the saphenous veins. An important finding was the definite increase in the potassium level of the coronary venous blood in proportion to the degree of ischaemia; the sodium level showed little change, and if anything tended to fall. But the most important and distinctive finding was that at the onset of VF the sodium and potassium concentrations in the coronary venous blood suddenly increase. As the VF continues, there is a progressive increase in lactic acid and a fall in pH, which is maximal at the onset of the VF. These findings are valid under normothermic conditions, and when there is no extracorporeal circulation. - The physiopathological and practical implications of these facts are discussed."}
{"id": "PMID:9919", "title": "Predicting the outcome of psychotherapy for schizophrenics. Relative contributions of patient, therapist, and treatment characteristics.", "content": "This study was designed to assess the relative prognostic importance of patient factors, therapist characterists, and treatment mode. The sample was 100 schizophrenic outpatients referred to a community mental health center following psychiatric hospitalization. Patients were randomly assigned to either group (N=50) or individual (N=50) psychotherapy. Criteria were rehospitalization and two clinician ratings--adjustment and social effectiveness--at a two-year follow-up. The best predictor of rehospitalization was the number of previous hospitalizations. The best predictor of adjustment status at two years was pretreatment adjustment level. Also, patients with good prognostic indices made relatively large gains. Predictors of outcome for group-treated patients did not differ from those for individually treated patients. Controlling for initial status, treatment mode was almost as good as predictor of adjustment gains as were other patient factors.", "contents": "Predicting the outcome of psychotherapy for schizophrenics. Relative contributions of patient, therapist, and treatment characteristics. This study was designed to assess the relative prognostic importance of patient factors, therapist characterists, and treatment mode. The sample was 100 schizophrenic outpatients referred to a community mental health center following psychiatric hospitalization. Patients were randomly assigned to either group (N=50) or individual (N=50) psychotherapy. Criteria were rehospitalization and two clinician ratings--adjustment and social effectiveness--at a two-year follow-up. The best predictor of rehospitalization was the number of previous hospitalizations. The best predictor of adjustment status at two years was pretreatment adjustment level. Also, patients with good prognostic indices made relatively large gains. Predictors of outcome for group-treated patients did not differ from those for individually treated patients. Controlling for initial status, treatment mode was almost as good as predictor of adjustment gains as were other patient factors."}
{"id": "PMID:9920", "title": "Different behaviour of thymus in hosts bearing skin homografts or ehrlich ascites carcinoma.", "content": "Thymus behaviour in A2G male mice transplanted with skin homografts or Ehrlich ascites carcinoma was followed for a period of 28 days. In comparison with control mice of the same strain in which only a slowly physiological involution of the thymus was observed, a marked, irreversible involution was seen in the tumour-bearing mice in contrast with the transient, completely recovered involution in animals transplanted with skin homografts. Thymus behaviour appears as the major structural difference between a host developping a strongly efficient or an inefficient immune response.", "contents": "Different behaviour of thymus in hosts bearing skin homografts or ehrlich ascites carcinoma. Thymus behaviour in A2G male mice transplanted with skin homografts or Ehrlich ascites carcinoma was followed for a period of 28 days. In comparison with control mice of the same strain in which only a slowly physiological involution of the thymus was observed, a marked, irreversible involution was seen in the tumour-bearing mice in contrast with the transient, completely recovered involution in animals transplanted with skin homografts. Thymus behaviour appears as the major structural difference between a host developping a strongly efficient or an inefficient immune response."}
{"id": "PMID:9921", "title": "Extracorporeal membrane oxygenation during bronchopulmonary lavage.", "content": "Extracorporeal membrane oxygenation (ECMO) in a venoarterial perfusion circuit was used to provide support of gas exchange during bronchopulmonary lavage in a 32-year-old man with pulmonary alveolar proteinosis and severe arterial hypoxemia. Prior to the lavage, Pao2 during mechanical ventilation with 100% oxygen and positive end-expiratory pressure was only 125 mm Hg. Extracorporeal perfusion at a flow rate of 3 liters/min, with oxygen delivery of 244 ml/min, increased the Pao2 to 227 mmHg and lowered the mean pulmonary artery pressure from 28 to 24 mm Hg. During bronchopulmonary lavage and ECMO, the Pao2 ranged between 46 and 96 mm Hg. After the procedure, pulmonary performance decidely improved. By reducing the chances of fatal hypoxemia, ECMO allowed treatment to be instituted for this potentially reversible disorder and proved helpful as a form of support during the management of pulmonary alveolar proteinosis when severe hypoxemia may have other wise precluded bronchopulmonary lavage.", "contents": "Extracorporeal membrane oxygenation during bronchopulmonary lavage. Extracorporeal membrane oxygenation (ECMO) in a venoarterial perfusion circuit was used to provide support of gas exchange during bronchopulmonary lavage in a 32-year-old man with pulmonary alveolar proteinosis and severe arterial hypoxemia. Prior to the lavage, Pao2 during mechanical ventilation with 100% oxygen and positive end-expiratory pressure was only 125 mm Hg. Extracorporeal perfusion at a flow rate of 3 liters/min, with oxygen delivery of 244 ml/min, increased the Pao2 to 227 mmHg and lowered the mean pulmonary artery pressure from 28 to 24 mm Hg. During bronchopulmonary lavage and ECMO, the Pao2 ranged between 46 and 96 mm Hg. After the procedure, pulmonary performance decidely improved. By reducing the chances of fatal hypoxemia, ECMO allowed treatment to be instituted for this potentially reversible disorder and proved helpful as a form of support during the management of pulmonary alveolar proteinosis when severe hypoxemia may have other wise precluded bronchopulmonary lavage."}
{"id": "PMID:9922", "title": "[On the toxicology of carbromal. I. Estimation of carbromal and its hypnotically active metabolites in rats and humans (author's transl)].", "content": "To analyze the toxic effects of carbromal it was necessary to have information on the concentrations of carbromal and of its metabolites in the organism. This information can be obtained by a simple method based on gaschromatography that allows rapid, specific, sensitive and quantitative estimation of carbromal and of its hypnotically active metabolites bromoethylbutyramide and ethylbutyrylurea. Employing different detectors (flame ionisation or electron capture detector) the limit of detection for carbromal and of its two metabolites was 2-3 nmoles/g of tissue. The method was used to study in rats the absorption and elimination of carbromal including biotransformation of carbromal to bromoethylbutyramide and ethylbutyrylurea. Both metabolites, significant amounts of which were found in serum and brain, distribute evenly between serum and brain as does carbromal. Both metabolites were detectable in the organism for a longer time than carbromal. Carbromal was given orally to 4 healthy volunteers at a dose of 1 g (4.2 nmoles). Highest serum concentrations (30 nmoles/ml) were found 30 min after ingestion. Serum concentrations declined rapidly. Twenty-four hours later 3-4% of the values were present in the serum. Beside carbromal considerable amounts (up to 20 nmoles/ml) of bromoethylbutyramide were detected but only small amounts (2-3 nmoles/ml) of ethylbutyrylurea. Peak concentrations of these metabolites were recorded 4-5 h after ingestion of carbromal. As was the case in rats both metabolites were present in the organism for a longer time than carbromal.", "contents": "[On the toxicology of carbromal. I. Estimation of carbromal and its hypnotically active metabolites in rats and humans (author's transl)]. To analyze the toxic effects of carbromal it was necessary to have information on the concentrations of carbromal and of its metabolites in the organism. This information can be obtained by a simple method based on gaschromatography that allows rapid, specific, sensitive and quantitative estimation of carbromal and of its hypnotically active metabolites bromoethylbutyramide and ethylbutyrylurea. Employing different detectors (flame ionisation or electron capture detector) the limit of detection for carbromal and of its two metabolites was 2-3 nmoles/g of tissue. The method was used to study in rats the absorption and elimination of carbromal including biotransformation of carbromal to bromoethylbutyramide and ethylbutyrylurea. Both metabolites, significant amounts of which were found in serum and brain, distribute evenly between serum and brain as does carbromal. Both metabolites were detectable in the organism for a longer time than carbromal. Carbromal was given orally to 4 healthy volunteers at a dose of 1 g (4.2 nmoles). Highest serum concentrations (30 nmoles/ml) were found 30 min after ingestion. Serum concentrations declined rapidly. Twenty-four hours later 3-4% of the values were present in the serum. Beside carbromal considerable amounts (up to 20 nmoles/ml) of bromoethylbutyramide were detected but only small amounts (2-3 nmoles/ml) of ethylbutyrylurea. Peak concentrations of these metabolites were recorded 4-5 h after ingestion of carbromal. As was the case in rats both metabolites were present in the organism for a longer time than carbromal."}
{"id": "PMID:9923", "title": "Late-onset acid maltase deficiency. Detection of patients and heterozygotes by urinary enzyme assay.", "content": "Daily urinary excretion of acid maltase (12.78 +/- 2.10 units/24 hr/mg of creatinine, in 11 normal adults) was significantly decreased in ten patients with late-onset acid maltase deficiency (1.33 +/- 0.16 units/24 hr; P less than .001) and 11 heterozygotes (3.27 +/- 0.62 units/24 hr; P less than .001). Maximal inhibition of urinary acid maltase activity by antibodies against human placental enzyme was 53% in controls, 30% in heterozygotes, and virtually absent in patients. Investigation of pH curves and enzyme inhibition by antibodies confirmed the presence in the kidney of an immunologically distinct \"extra\" maltase enzyme active at acid pH. Whether acid maltase in normal urine originates in the kidney or cells of the lower urinary tract, the enzyme defect seems to be expressed in these cells in late-onset acid maltase deficiency.", "contents": "Late-onset acid maltase deficiency. Detection of patients and heterozygotes by urinary enzyme assay. Daily urinary excretion of acid maltase (12.78 +/- 2.10 units/24 hr/mg of creatinine, in 11 normal adults) was significantly decreased in ten patients with late-onset acid maltase deficiency (1.33 +/- 0.16 units/24 hr; P less than .001) and 11 heterozygotes (3.27 +/- 0.62 units/24 hr; P less than .001). Maximal inhibition of urinary acid maltase activity by antibodies against human placental enzyme was 53% in controls, 30% in heterozygotes, and virtually absent in patients. Investigation of pH curves and enzyme inhibition by antibodies confirmed the presence in the kidney of an immunologically distinct \"extra\" maltase enzyme active at acid pH. Whether acid maltase in normal urine originates in the kidney or cells of the lower urinary tract, the enzyme defect seems to be expressed in these cells in late-onset acid maltase deficiency."}
{"id": "PMID:9925", "title": "Aspects of the use of lithium for the non-psychiatrist.", "content": "Lithium carbonate is commonly used in psychiatry, particularly in the management of the manic-depressive syndrome. It is also being increasingly tried in a variety of physical disorders. This essentially practical article summarizes important non-psychiatric aspects of the use of the drug, including its less common actions. Contra-indications to the use of lithium are discussed, and the management of lithium intoxication is outlined.", "contents": "Aspects of the use of lithium for the non-psychiatrist. Lithium carbonate is commonly used in psychiatry, particularly in the management of the manic-depressive syndrome. It is also being increasingly tried in a variety of physical disorders. This essentially practical article summarizes important non-psychiatric aspects of the use of the drug, including its less common actions. Contra-indications to the use of lithium are discussed, and the management of lithium intoxication is outlined."}
{"id": "PMID:9926", "title": "Homosexuality treated adventitiously in a stuttering therapy program: a case report presenting a heterophobic orientation.", "content": "The heterophobic orientation toward treatment of homosexuality is discussed. A case report is presented where homosexuality apparently \"spontaneously remitted\" and heterosexuality was instated while the patient underwent treatment for stuttering. The change in sexual orientation is interpreted as possibly adventitiously induced through generalization effects from treatment of the relevant phobic aspects of the stuttering problem to the associated social aspects of the sexual problem.", "contents": "Homosexuality treated adventitiously in a stuttering therapy program: a case report presenting a heterophobic orientation. The heterophobic orientation toward treatment of homosexuality is discussed. A case report is presented where homosexuality apparently \"spontaneously remitted\" and heterosexuality was instated while the patient underwent treatment for stuttering. The change in sexual orientation is interpreted as possibly adventitiously induced through generalization effects from treatment of the relevant phobic aspects of the stuttering problem to the associated social aspects of the sexual problem."}
{"id": "PMID:9930", "title": "[Alterations of cat papillary muscle mechanics induced by changes of preload under variation of physical and chemical parameters (author's transl)].", "content": "A rapid change in length of cat papillary muscle induces two reciprocal diastolic and systolic processes: stretching causes a viscoelastic relaxation of the muscle. The opposite behavior is observed after abrupt releases when - subsequent to an increase in resting tension - diastolic force attains its new equilibrium. The stretch-induced process of relaxation is accompanied by a transient decrease in mechanogram amplitudes; a release is accordingly followed by a temporary increase in isometric muscle performance. The mechanograms of the steady state prove to be the function of the degree of stretch or release, whereas muscle contractions in the early phase of stress relaxation depend on the contractile state before the change in length. All interventions which augment developed tension (increased calcium, decreased potassium, increased or decreased sodium concentrations, strontium, postextrasystolic potentiation, sympathicomimetic agents, frequency potentiation) diminish the transient phenomena due to stretch, whereas low frequency or a lesser intensity of electromechanical coupling (Hexobarbital, Iproveratril, Desoxycorticosteron, Ryanodine) increases them. A decrease of bath temperature enhances the transient increase in force due to a release or an initial reduction of isometric tension after a sudden stretch, although the absolute forces increase. No substantial changes could be observed in reserpinized cats with beta-blocking agents or under hypoxia. It is supposed that alterations in the time course of the action potential could be related to post-stretch and post-release systolic phenomena. A final interpretation of mechanical and electrical events after stretch and release is not possible with the methods used in these experiments.", "contents": "[Alterations of cat papillary muscle mechanics induced by changes of preload under variation of physical and chemical parameters (author's transl)]. A rapid change in length of cat papillary muscle induces two reciprocal diastolic and systolic processes: stretching causes a viscoelastic relaxation of the muscle. The opposite behavior is observed after abrupt releases when - subsequent to an increase in resting tension - diastolic force attains its new equilibrium. The stretch-induced process of relaxation is accompanied by a transient decrease in mechanogram amplitudes; a release is accordingly followed by a temporary increase in isometric muscle performance. The mechanograms of the steady state prove to be the function of the degree of stretch or release, whereas muscle contractions in the early phase of stress relaxation depend on the contractile state before the change in length. All interventions which augment developed tension (increased calcium, decreased potassium, increased or decreased sodium concentrations, strontium, postextrasystolic potentiation, sympathicomimetic agents, frequency potentiation) diminish the transient phenomena due to stretch, whereas low frequency or a lesser intensity of electromechanical coupling (Hexobarbital, Iproveratril, Desoxycorticosteron, Ryanodine) increases them. A decrease of bath temperature enhances the transient increase in force due to a release or an initial reduction of isometric tension after a sudden stretch, although the absolute forces increase. No substantial changes could be observed in reserpinized cats with beta-blocking agents or under hypoxia. It is supposed that alterations in the time course of the action potential could be related to post-stretch and post-release systolic phenomena. A final interpretation of mechanical and electrical events after stretch and release is not possible with the methods used in these experiments."}
{"id": "PMID:9940", "title": "Facultative anaerobiosis in molluscs.", "content": "The glycolytic fermentation of molluscs is rather complex. Multiple end products accumulate (lactate, alanine, octopine, succinate, propionate, acetate and CO2), which are partly formed in the cytoplasm and partly in the mitochondrion. Various schemes have been presented to account for these end products as well as for the maintenance of the redox balance. With respect to the role of alanine there are two opinions: (1) alanine accumulation is continuous and is essential for the generation of the mitochondrial NADH required in the reduction of fumarate and (2) succinate and alanine (initial end products) accumulate in different compartments and their accumulation occurs independently. Both statements are evaluated in the light of the latest experimental observations including the regulatory properties at the phosphoenolpyruvate branchpoint and the effect of pH and 'energy charge'. For nervous tissue the function of oxygen can be replaced by the lipochrome pigment, which enables carbohydrates to be totally oxidized to CO2 and water. The simultaneous mobilization of carbohydrates and amino acids is not supported by the experimental data. Various advantages of the glycolytic fermentation in molluscs as compared with classical glycolysis in skeletal muscle are discussed.", "contents": "Facultative anaerobiosis in molluscs. The glycolytic fermentation of molluscs is rather complex. Multiple end products accumulate (lactate, alanine, octopine, succinate, propionate, acetate and CO2), which are partly formed in the cytoplasm and partly in the mitochondrion. Various schemes have been presented to account for these end products as well as for the maintenance of the redox balance. With respect to the role of alanine there are two opinions: (1) alanine accumulation is continuous and is essential for the generation of the mitochondrial NADH required in the reduction of fumarate and (2) succinate and alanine (initial end products) accumulate in different compartments and their accumulation occurs independently. Both statements are evaluated in the light of the latest experimental observations including the regulatory properties at the phosphoenolpyruvate branchpoint and the effect of pH and 'energy charge'. For nervous tissue the function of oxygen can be replaced by the lipochrome pigment, which enables carbohydrates to be totally oxidized to CO2 and water. The simultaneous mobilization of carbohydrates and amino acids is not supported by the experimental data. Various advantages of the glycolytic fermentation in molluscs as compared with classical glycolysis in skeletal muscle are discussed."}
{"id": "PMID:9941", "title": "Adaptations of enzymes for regulation of catalytic function.", "content": "1. Enzymes must not only be extremely effective catalysts, but must also be the operating components of very sensitive and sophisticated regulatory systems. Appropriate evolutionary adjustment of the properties of different enzymes causes the sites that bind typical metabolic intermediates to be only partially saturated in vivo, thus allowing flexibility for control by variation in ligand concentration. In contrast, sites that bind such coupling agents as the pyridine and adenine nucleotides seem to be virtually saturated. Thus the ratios, rather than the absolute concentrations, of these compounds are important in metabolic regulation. This type of response is esstial to the function of these compounds simultaneously as thermodynamic energy transducers and modifiers in the kinetics regulatory system. 2. Reaction orders of two to four are frequently encountered. They appear to be essenital to biochemical homoeostasis, which is the maintenance of nearly constant substrate concentrations at the expense of wide variation in flux rates. 3. The strategies of enzyme adaptation are general, but the actual adaptations of enzymes are highly specific, reflecting the place of the enzyme in a metabolic sequence, the place of the sequence in the metabolism of the cell and, in complex organisms, the function of the cell, and of the organ or tissue of which it is a part, in the organism. Patterns of adaptation must be almost infinitely varied. A few are presently known in outline, but probably none as yet in detail. Several examples are discussed.", "contents": "Adaptations of enzymes for regulation of catalytic function. 1. Enzymes must not only be extremely effective catalysts, but must also be the operating components of very sensitive and sophisticated regulatory systems. Appropriate evolutionary adjustment of the properties of different enzymes causes the sites that bind typical metabolic intermediates to be only partially saturated in vivo, thus allowing flexibility for control by variation in ligand concentration. In contrast, sites that bind such coupling agents as the pyridine and adenine nucleotides seem to be virtually saturated. Thus the ratios, rather than the absolute concentrations, of these compounds are important in metabolic regulation. This type of response is esstial to the function of these compounds simultaneously as thermodynamic energy transducers and modifiers in the kinetics regulatory system. 2. Reaction orders of two to four are frequently encountered. They appear to be essenital to biochemical homoeostasis, which is the maintenance of nearly constant substrate concentrations at the expense of wide variation in flux rates. 3. The strategies of enzyme adaptation are general, but the actual adaptations of enzymes are highly specific, reflecting the place of the enzyme in a metabolic sequence, the place of the sequence in the metabolism of the cell and, in complex organisms, the function of the cell, and of the organ or tissue of which it is a part, in the organism. Patterns of adaptation must be almost infinitely varied. A few are presently known in outline, but probably none as yet in detail. Several examples are discussed."}
{"id": "PMID:9948", "title": "Early changes in the arterial wall of chickens fed a cholesterol diet.", "content": "A total of 160 1-2 day old chickens were fed a 2% cholesterol diet for a period of 8 to 42 days and compared with an equal number of controls. Aortas were analyzed for various indexes of reactivity of connective tissue, cholesterol content and scanning electron microscopy (SEM) characteristics of the endothelial lining. Cholesterol feeding for a period up to 6 weeks resulted in doubling the level of serum cholesterol. It was, however, without effect on the activity of prolyl hydroxylase, lysyl oxidase, collagenase and collagen content in the aortic wall. As early as 3 weeks of feeding significant changes occurred in total and esterified cholesterol content. At the same time endothelial cells were characteristically contracted with several long cytoplasmic elongations and protrusions. A significant decrease of activity of the above enzymes was found in aortic tissue with increased age of the chicken. Collagen content in aortas increased with age of chickens. It is concluded that cholesterol as an atherogenic agent induces marked changes in endothelial cells and lipids of chicken aorta at earlier periods, prior to the activation of connective tissue.", "contents": "Early changes in the arterial wall of chickens fed a cholesterol diet. A total of 160 1-2 day old chickens were fed a 2% cholesterol diet for a period of 8 to 42 days and compared with an equal number of controls. Aortas were analyzed for various indexes of reactivity of connective tissue, cholesterol content and scanning electron microscopy (SEM) characteristics of the endothelial lining. Cholesterol feeding for a period up to 6 weeks resulted in doubling the level of serum cholesterol. It was, however, without effect on the activity of prolyl hydroxylase, lysyl oxidase, collagenase and collagen content in the aortic wall. As early as 3 weeks of feeding significant changes occurred in total and esterified cholesterol content. At the same time endothelial cells were characteristically contracted with several long cytoplasmic elongations and protrusions. A significant decrease of activity of the above enzymes was found in aortic tissue with increased age of the chicken. Collagen content in aortas increased with age of chickens. It is concluded that cholesterol as an atherogenic agent induces marked changes in endothelial cells and lipids of chicken aorta at earlier periods, prior to the activation of connective tissue."}
{"id": "PMID:9950", "title": "Isoprenaline antagonism of cardioselective beta-adrenergic receptor blocking agents on human and rat adipocytes.", "content": "1. The beta-adrenergic blocking potencies of practolol, ICI 66082, tolamolol, acebutolol, H 93/26, H 87/07, pindolol and Ro 3-4787 were compared with that of propranolol, on human and rat adipocytes. 2. A good correlation was found between the potencies on adipocytes of the two species but not between our results and literature data on antagonism of isopernaline tachycardia in the anaesthetized cat. 3. The results indicate that differences between adrenergic beta-receptors in heart and adipose tissue may be detected using cardioselective beta-adrenergic receptor blocking agents.", "contents": "Isoprenaline antagonism of cardioselective beta-adrenergic receptor blocking agents on human and rat adipocytes. 1. The beta-adrenergic blocking potencies of practolol, ICI 66082, tolamolol, acebutolol, H 93/26, H 87/07, pindolol and Ro 3-4787 were compared with that of propranolol, on human and rat adipocytes. 2. A good correlation was found between the potencies on adipocytes of the two species but not between our results and literature data on antagonism of isopernaline tachycardia in the anaesthetized cat. 3. The results indicate that differences between adrenergic beta-receptors in heart and adipose tissue may be detected using cardioselective beta-adrenergic receptor blocking agents."}
{"id": "PMID:9952", "title": "Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man.", "content": "Cimetidine, a new H2-receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half-life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended.", "contents": "Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man. Cimetidine, a new H2-receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half-life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended."}
{"id": "PMID:9953", "title": "Inhibition of gastric emptying and drug absorption by narcotic analgesics.", "content": "The effect of intramuscular pethidine or diamorphine on gastric emptying and the absorption of orally administered paracetamol was assessed in eight normal subjects. 2 Both drugs produced a significant and striking delay in gastric emptying and absorption of paracetamol. 3 It seems inevitable that pethidine and diamorphine will retard the absorption of other orally administered drugs.", "contents": "Inhibition of gastric emptying and drug absorption by narcotic analgesics. The effect of intramuscular pethidine or diamorphine on gastric emptying and the absorption of orally administered paracetamol was assessed in eight normal subjects. 2 Both drugs produced a significant and striking delay in gastric emptying and absorption of paracetamol. 3 It seems inevitable that pethidine and diamorphine will retard the absorption of other orally administered drugs."}
{"id": "PMID:9954", "title": "The effects of atenolol (tenormin) and methyldopa on simple tests of central nervous function.", "content": "Two identical studies, one comparing the effect of single doses of a new beta-adrenoceptor blocker, atenolol (Tenormin) (50 mg and 100 mg) and placebo, and the other comparing the effect of single doses of methyldopa (250 mg and 500 mg) and placebo, in healthy volunteers, were carried out. 2 In both studies the effect of the drugs upon reaction time, critical flicker frequency, subjective drowsiness, pulse rate and blood pressure was measured. 3 Atenolol produced no effect upon reaction time, critical flicker frequency or subjective feelings, while methyldopa produced a statistically significant prolongation of reaction time and a statistically significant increase in the subjective sensation of drowsiness. 4 Atenolol produced statistically significant reductions in systolic and diastolic blood pressure and in pulse rate while methyldopa was without effect. 5 It is concluded that atenolol is unlikely to produce the side effects of sedation or drowsiness.", "contents": "The effects of atenolol (tenormin) and methyldopa on simple tests of central nervous function. Two identical studies, one comparing the effect of single doses of a new beta-adrenoceptor blocker, atenolol (Tenormin) (50 mg and 100 mg) and placebo, and the other comparing the effect of single doses of methyldopa (250 mg and 500 mg) and placebo, in healthy volunteers, were carried out. 2 In both studies the effect of the drugs upon reaction time, critical flicker frequency, subjective drowsiness, pulse rate and blood pressure was measured. 3 Atenolol produced no effect upon reaction time, critical flicker frequency or subjective feelings, while methyldopa produced a statistically significant prolongation of reaction time and a statistically significant increase in the subjective sensation of drowsiness. 4 Atenolol produced statistically significant reductions in systolic and diastolic blood pressure and in pulse rate while methyldopa was without effect. 5 It is concluded that atenolol is unlikely to produce the side effects of sedation or drowsiness."}
{"id": "PMID:9963", "title": "Effect of N-desmethyldiazepam (nordiazepam) and a precursor, potassium clorazepate, on sleep in man.", "content": "1 The effect of N-desmethyldiazepam (nordiazepam, 5 and 10 mg) and potassium clorazepate (15 mg, a precursor of nordiazepam) on sleep was studied in six healthy adult males. Electroencephalography (EEG) was used for sleep measures, and analogue scales were used for subjective assessments of well-being and sleep quality. 2 Effects on total sleep time were limited to the night of ingestion. There were increases with nordiazepam (5 and 10 mg) (P = 0.05) and 0.001 respectively), and with clorazepate (15 mg) (P = 0.01). Sleep onset latencies were shortened, particularly with nordiazepam, and awakening to stage 0 activity was reduced, by both drugs. The latency to stage 3 was reduced by nordiazepam (5 and 10 mg) (P = 0.05). 3 There were no effects of nordiazepam (5 mg) on the duration (min) of sleep stages. Nordiazepam (10 mg) and clorazepate (15 mg) reduced the duration of stage 0 and stage 1, and there were increases in stage 2. Reduced stage 1 and increased stage 2 sleep were observed during the recovery night. No effects were observed with stage 3, but there was evidence that stage 4 activity was depressed on the recovery night only. No effects were observed on REM sleep, except that the appearnace of the first REM period was delayed with clorazepate (15 mg) P = 0.01). The effect of nordiazepam (10 mg) and clorazepate (15 mg) were comparable, and each modified sleep for about 28-30 h after ingestion. 4 With nordiazepam (10 mg) and clorazepate (15 mg) the subjects, as a group, reported improved sleep, but subjective assessments of well-being were not altered. Correlations were calculated for sleep measures and subjective assessments.", "contents": "Effect of N-desmethyldiazepam (nordiazepam) and a precursor, potassium clorazepate, on sleep in man. 1 The effect of N-desmethyldiazepam (nordiazepam, 5 and 10 mg) and potassium clorazepate (15 mg, a precursor of nordiazepam) on sleep was studied in six healthy adult males. Electroencephalography (EEG) was used for sleep measures, and analogue scales were used for subjective assessments of well-being and sleep quality. 2 Effects on total sleep time were limited to the night of ingestion. There were increases with nordiazepam (5 and 10 mg) (P = 0.05) and 0.001 respectively), and with clorazepate (15 mg) (P = 0.01). Sleep onset latencies were shortened, particularly with nordiazepam, and awakening to stage 0 activity was reduced, by both drugs. The latency to stage 3 was reduced by nordiazepam (5 and 10 mg) (P = 0.05). 3 There were no effects of nordiazepam (5 mg) on the duration (min) of sleep stages. Nordiazepam (10 mg) and clorazepate (15 mg) reduced the duration of stage 0 and stage 1, and there were increases in stage 2. Reduced stage 1 and increased stage 2 sleep were observed during the recovery night. No effects were observed with stage 3, but there was evidence that stage 4 activity was depressed on the recovery night only. No effects were observed on REM sleep, except that the appearnace of the first REM period was delayed with clorazepate (15 mg) P = 0.01). The effect of nordiazepam (10 mg) and clorazepate (15 mg) were comparable, and each modified sleep for about 28-30 h after ingestion. 4 With nordiazepam (10 mg) and clorazepate (15 mg) the subjects, as a group, reported improved sleep, but subjective assessments of well-being were not altered. Correlations were calculated for sleep measures and subjective assessments."}
{"id": "PMID:9964", "title": "Assessment of drugs in schizophrenia. Basic trial design.", "content": "Clinical trials with major tranquilizers must take into account the clinical features of patients with schizophrenia and pharmacokinetic and pharmacodynamic properties of the drug. The objectives of the trial must be carefully defined so that appropriate selection criteria for patients, rating instruments and dosage schedules can be selected. It is useful to monitor physiological and biochemical actions of major tranquilizers as well as the clinical effects.", "contents": "Assessment of drugs in schizophrenia. Basic trial design. Clinical trials with major tranquilizers must take into account the clinical features of patients with schizophrenia and pharmacokinetic and pharmacodynamic properties of the drug. The objectives of the trial must be carefully defined so that appropriate selection criteria for patients, rating instruments and dosage schedules can be selected. It is useful to monitor physiological and biochemical actions of major tranquilizers as well as the clinical effects."}
{"id": "PMID:9965", "title": "Assessment of drugs in schizophrenia. Asessment of drug-induced extrapyramidal reactions and of drugs given for their control.", "content": "I have tried to bring out some of the important methodological problems found in examining the effectiveness of drugs used in the control of druginduced parkinsonism by referring mainly to studies in which I have taken part. I hope I have shown that the whole topic is far less well understood than is often assumed. The main points may be summarized as follows: there is doubt as to whether many of the drugs used in controlling drug-induced parkinsonism are really effective; the results of many studies are conflicting; many studies contain serious flaws in design; methods for assessing extrapyramidal signs are not well developed; we are ignorant of the way in which drug-induced extrapyramidal signs change spontaneously. There is a clear need for further research in this area to improve techniques of assessment, to provide basic information on drug-induced syndromes, and to rigorously examine the efficacy of the drugs used in controlling them.", "contents": "Assessment of drugs in schizophrenia. Asessment of drug-induced extrapyramidal reactions and of drugs given for their control. I have tried to bring out some of the important methodological problems found in examining the effectiveness of drugs used in the control of druginduced parkinsonism by referring mainly to studies in which I have taken part. I hope I have shown that the whole topic is far less well understood than is often assumed. The main points may be summarized as follows: there is doubt as to whether many of the drugs used in controlling drug-induced parkinsonism are really effective; the results of many studies are conflicting; many studies contain serious flaws in design; methods for assessing extrapyramidal signs are not well developed; we are ignorant of the way in which drug-induced extrapyramidal signs change spontaneously. There is a clear need for further research in this area to improve techniques of assessment, to provide basic information on drug-induced syndromes, and to rigorously examine the efficacy of the drugs used in controlling them."}
{"id": "PMID:9967", "title": "Residual effects and skills related to driving after a single oral administration of diazepam, medazepam or lorazepam.", "content": "Psychomotor skills and visual functions related to driving were measured double-blind cross-over in ten healthy volunteers before, and 1,3,5 and 7 h after a single oral administration of diazepam (10mg), medazepam (15 mg) or lorazepam (2.5 mg). The late effects of lorazepam were tested in seven other subjects 12 and 24 h after the administration. Lorazepam impaired almost all the measured skills more (P less than 0.05 to 0.001) than diazepam, medizepam or the placebo. The lorazepam impairment of reactive skills and flicker fusion discrimination remained statistically significant (P less than 0.05) for as long as 12 h. Medazepam impaired only reactive skills and flicker fusion, the latter remaining impaired (P less than 0.05) for as long a 5 h after the administration. The magnitude  and duration of the effects of diazepam were intermediate between those of lorazepam and medazepam. Diazepam impaired perceptual speed and reactive and co-ordinative skills as well as flicker fusion discrimination and visual parameters related to driving. Slight impairments in performance were measurable for up to 5 h after administration but at 7 h the results resembled those measured after the placebo. The lack of alterations in adaptation to darkness, sensitivity to brightness or visual discrimination ability in bright counterlight at a time when flicker fusion discrimination was severely depressed suggests that an impaired ability to discriminate flickering light is of no or little clinical significance to driving ability. It is concluded that patients receiving a 2.5 mg dose of lorazepam should not drive or operate machinery for 24 h after the administration. After diazepam (10 mg) or medazepam (15 mg) patients should refrain from driving or participating inskilled performances for only 5 to 7 hours.", "contents": "Residual effects and skills related to driving after a single oral administration of diazepam, medazepam or lorazepam. Psychomotor skills and visual functions related to driving were measured double-blind cross-over in ten healthy volunteers before, and 1,3,5 and 7 h after a single oral administration of diazepam (10mg), medazepam (15 mg) or lorazepam (2.5 mg). The late effects of lorazepam were tested in seven other subjects 12 and 24 h after the administration. Lorazepam impaired almost all the measured skills more (P less than 0.05 to 0.001) than diazepam, medizepam or the placebo. The lorazepam impairment of reactive skills and flicker fusion discrimination remained statistically significant (P less than 0.05) for as long as 12 h. Medazepam impaired only reactive skills and flicker fusion, the latter remaining impaired (P less than 0.05) for as long a 5 h after the administration. The magnitude  and duration of the effects of diazepam were intermediate between those of lorazepam and medazepam. Diazepam impaired perceptual speed and reactive and co-ordinative skills as well as flicker fusion discrimination and visual parameters related to driving. Slight impairments in performance were measurable for up to 5 h after administration but at 7 h the results resembled those measured after the placebo. The lack of alterations in adaptation to darkness, sensitivity to brightness or visual discrimination ability in bright counterlight at a time when flicker fusion discrimination was severely depressed suggests that an impaired ability to discriminate flickering light is of no or little clinical significance to driving ability. It is concluded that patients receiving a 2.5 mg dose of lorazepam should not drive or operate machinery for 24 h after the administration. After diazepam (10 mg) or medazepam (15 mg) patients should refrain from driving or participating inskilled performances for only 5 to 7 hours."}
{"id": "PMID:9968", "title": "Assessment of alpha- and beta-adrenoceptor blocking actions of labetalol.", "content": "Isoprenaline dose-response curves plotting increases in heart rate before and after labetalol are suggestive of competitive antagonism at beta-adrenoceptor sites. Phenylephrine dose-response curves using increases in systolic pressure before and after labetalol are suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of alpha:beta-adrenoceptor antagonism induced by labetalol is approximately 1:3. Peak pharmacological responses after a single oral dose of labetalol (400 mg) occurred between 90-120 min after administration.", "contents": "Assessment of alpha- and beta-adrenoceptor blocking actions of labetalol. Isoprenaline dose-response curves plotting increases in heart rate before and after labetalol are suggestive of competitive antagonism at beta-adrenoceptor sites. Phenylephrine dose-response curves using increases in systolic pressure before and after labetalol are suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of alpha:beta-adrenoceptor antagonism induced by labetalol is approximately 1:3. Peak pharmacological responses after a single oral dose of labetalol (400 mg) occurred between 90-120 min after administration."}
{"id": "PMID:9969", "title": "The sensitivity of a malignant cell line to hyperthermia (42 degrees C) at low intracellular pH.", "content": "The postulate that low intracellular pH acts as a preconditioner for the destructuve effects of hyperthermia (42 degrees C) was examined, using  a heat-sensitive line of malignant cells derived from rat mammary gland (SDB). Intracellular pH (pHi) was measured indirectly, from the distribution of the weak, non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolidinedione (DMO) between intra- and extra-cellular water. Respiration, aerobic and anaerobic and anaerobic glycolysis of the cells were studied at normal pHi (pH 7-0-7-4) or at low pHi (pH 6-2-6-6) and at 38 degrees C or 42 degrees C over 6 h in Warburg manometers; the ability of the cells to replicate in culture was examined after 3 h or 6 h incubation in the flasks. The relationship between pHi and extracellular pH (pHe) depended upon the buffer system used and the exact pH in question; no assumption regarding pHi based only on pHe measurement could be made. At 38 degrees C and low pHi, the Pasteur effect became negative due to a relatively greater inhibition of anaerobic than aerobic glycolysis. Respiration was unaffected and cell replicative ability unimpaired. At 42 degrees C and normal pHi, respiration was totally inhibited after 4 h and the Pasteur effect was decreased, in this case due to a compensatory increase in aerobic glycolysis without alteration in anaerobic CO2 production. Low pHi in the presence of hyperthermia enabled cell respiration to continue at a reduced level with no further change in glycolysis. There was delayed cell replication after 3 h at 42 degrees C and inability to multiply following 6 h hyperthermia: low pHi did not influence these results. It is concluded that with these cancer cells, pHi values maintained in the region of 1-0 pH unit below normal for 6 h had no deleterious effect on the cells. No sensitizing effect of the low pHi for the destructive effect of hyperthermia on the cells was observed.", "contents": "The sensitivity of a malignant cell line to hyperthermia (42 degrees C) at low intracellular pH. The postulate that low intracellular pH acts as a preconditioner for the destructuve effects of hyperthermia (42 degrees C) was examined, using  a heat-sensitive line of malignant cells derived from rat mammary gland (SDB). Intracellular pH (pHi) was measured indirectly, from the distribution of the weak, non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolidinedione (DMO) between intra- and extra-cellular water. Respiration, aerobic and anaerobic and anaerobic glycolysis of the cells were studied at normal pHi (pH 7-0-7-4) or at low pHi (pH 6-2-6-6) and at 38 degrees C or 42 degrees C over 6 h in Warburg manometers; the ability of the cells to replicate in culture was examined after 3 h or 6 h incubation in the flasks. The relationship between pHi and extracellular pH (pHe) depended upon the buffer system used and the exact pH in question; no assumption regarding pHi based only on pHe measurement could be made. At 38 degrees C and low pHi, the Pasteur effect became negative due to a relatively greater inhibition of anaerobic than aerobic glycolysis. Respiration was unaffected and cell replicative ability unimpaired. At 42 degrees C and normal pHi, respiration was totally inhibited after 4 h and the Pasteur effect was decreased, in this case due to a compensatory increase in aerobic glycolysis without alteration in anaerobic CO2 production. Low pHi in the presence of hyperthermia enabled cell respiration to continue at a reduced level with no further change in glycolysis. There was delayed cell replication after 3 h at 42 degrees C and inability to multiply following 6 h hyperthermia: low pHi did not influence these results. It is concluded that with these cancer cells, pHi values maintained in the region of 1-0 pH unit below normal for 6 h had no deleterious effect on the cells. No sensitizing effect of the low pHi for the destructive effect of hyperthermia on the cells was observed."}
{"id": "PMID:9970", "title": "A comparison of the pupilloconstrictor effect of pilocarpine solution administered to the conjunctival sac as a single drop or as a continuous infusion in normal subjects.", "content": "Pilocarpine was administered into the conjunctival sac of normal volunteers by single-drop administration or by continuous infusion of a solution to the inner canthus by means of a fine Silastic tube. Using pupilloconstriction as a measure of response it was shown that infusion with a 0-01 per cent solution of pilocarpine was as effective as a single drop of 0-5 per cent pilocarpine. The response to the single drop was faster at onset. It was demonstrated that at pH 7-2 pilocarpine was more effective than at acid pH. The infusion method is simple to use, comfortable for long periods, has potential for reducing the need for frequent drop administration and for reducing the total amount of drug administered, and could be used for drugs other than pilocarpine.", "contents": "A comparison of the pupilloconstrictor effect of pilocarpine solution administered to the conjunctival sac as a single drop or as a continuous infusion in normal subjects. Pilocarpine was administered into the conjunctival sac of normal volunteers by single-drop administration or by continuous infusion of a solution to the inner canthus by means of a fine Silastic tube. Using pupilloconstriction as a measure of response it was shown that infusion with a 0-01 per cent solution of pilocarpine was as effective as a single drop of 0-5 per cent pilocarpine. The response to the single drop was faster at onset. It was demonstrated that at pH 7-2 pilocarpine was more effective than at acid pH. The infusion method is simple to use, comfortable for long periods, has potential for reducing the need for frequent drop administration and for reducing the total amount of drug administered, and could be used for drugs other than pilocarpine."}
{"id": "PMID:9971", "title": "Ribose recognition by ribonuclease T1: difference spectral binding studies with guanosine and deoxyguanosine.", "content": "The binding of ribonuclease T1 with guanosine (Guo) and deoxyguanosine (dGuo) was studied in experiments employing ultraviolet difference spectroscopy in the pH range 3-9 at 0.2 M ionic strength and 25 degrees C. Similar experiments were also conducted with psi-carboxymethyl-glutamate-58 ribonuclease T1 at pH 5.0. At most pH values the characteristic difference spectrum and association constant were obtained. The binding constant for dGuo was  approximately 550 M-1 and did not significantly vary in the pH range 3.5-9.0. The binding constant for Guo increased from pH 3.5 to 5.0, was constant between pH 5.0 and 7.0 (approximately 3200 M-1), and decreased at higher pH values. The binding of Guo and dGuo with ribonuclease T1 could also be distinguished in terms of the wavelength for maximal difference absorbance, lambdamax, between pH 5.0 and 7.0. At higher and lower pH values, lambdamax for Guo approached that found fr dGuo. On the other hand, the value of the binding constant (approximately6500 M-1) and the nature of the difference spectra for Guo and dGuo binding with lambdamax-carboxymethyl-glutamate-58-ribonuclease T1 at pH 5.0 were identical. These results suggest that the discrete interaction of the Guo 2'-hydroxyl group with ribonuclease T1 involves the lambda-carboxylate of glutamate-58 and an imidazolium group at the active site.", "contents": "Ribose recognition by ribonuclease T1: difference spectral binding studies with guanosine and deoxyguanosine. The binding of ribonuclease T1 with guanosine (Guo) and deoxyguanosine (dGuo) was studied in experiments employing ultraviolet difference spectroscopy in the pH range 3-9 at 0.2 M ionic strength and 25 degrees C. Similar experiments were also conducted with psi-carboxymethyl-glutamate-58 ribonuclease T1 at pH 5.0. At most pH values the characteristic difference spectrum and association constant were obtained. The binding constant for dGuo was  approximately 550 M-1 and did not significantly vary in the pH range 3.5-9.0. The binding constant for Guo increased from pH 3.5 to 5.0, was constant between pH 5.0 and 7.0 (approximately 3200 M-1), and decreased at higher pH values. The binding of Guo and dGuo with ribonuclease T1 could also be distinguished in terms of the wavelength for maximal difference absorbance, lambdamax, between pH 5.0 and 7.0. At higher and lower pH values, lambdamax for Guo approached that found fr dGuo. On the other hand, the value of the binding constant (approximately6500 M-1) and the nature of the difference spectra for Guo and dGuo binding with lambdamax-carboxymethyl-glutamate-58-ribonuclease T1 at pH 5.0 were identical. These results suggest that the discrete interaction of the Guo 2'-hydroxyl group with ribonuclease T1 involves the lambda-carboxylate of glutamate-58 and an imidazolium group at the active site."}
{"id": "PMID:9972", "title": "Bovine brain purine-nucleoside phosphorylase purification, characterization, and catalytic mechanism.", "content": "Bovine brain purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) was purified to homogeneity at a specific activity of 78 mumol min-1 mg of protein-1. A molecular weight of 78 000-80 000 was calculated for the native enzyme by fel filtration on Sephadex. Gel electrophoresis in the presence of sodium dodecyl sulfate indicated subunits of molecular weight of 38 000. Chemical and kinetic studies strongly implicated histidine and cysteine as catalytic groups at the active site of the enzyme. The pKa's determined for ionizable groups at the active site of the free enzyme were 5.8 and 8.2. Enzyme completely inactivated by p-chloromercuribenzoate was partially reactivated enzyme. A strong susceptibility to photooxidation in presence of methylene blue was observed. Photoinactivation was pH dependent, implicating histidine as the susceptible group at the active site. A rapid loss of catalytic activity upon incubation at 55 degrees C suggested heat lability. An activation energy of 9.6 kcal/mol was calculated. The nature of the catalytic mechanism of the enzyme was investigated, and initial velocity studies showed linear converging patterns of double-reciprocal plots of the data, consistent with a sequential catalytic mechanism. The product inhibition pattern was at variance with both the ordered Bi-Bi and random mechanisms. The observed competition between purine and nucleoside, and between inorganic orthophosphate and ribose 1-phosphate for this ordered mechanism, suggest a Theorell-Chance mechanism. Michaelis constants determined for substrates of the enzyme were 4.35 X 10(-5) M for guanosine, 3.00 X 10(-5) M for guanine, and 2.15 X 10(-2) M for inorganic orthophosphate.", "contents": "Bovine brain purine-nucleoside phosphorylase purification, characterization, and catalytic mechanism. Bovine brain purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) was purified to homogeneity at a specific activity of 78 mumol min-1 mg of protein-1. A molecular weight of 78 000-80 000 was calculated for the native enzyme by fel filtration on Sephadex. Gel electrophoresis in the presence of sodium dodecyl sulfate indicated subunits of molecular weight of 38 000. Chemical and kinetic studies strongly implicated histidine and cysteine as catalytic groups at the active site of the enzyme. The pKa's determined for ionizable groups at the active site of the free enzyme were 5.8 and 8.2. Enzyme completely inactivated by p-chloromercuribenzoate was partially reactivated enzyme. A strong susceptibility to photooxidation in presence of methylene blue was observed. Photoinactivation was pH dependent, implicating histidine as the susceptible group at the active site. A rapid loss of catalytic activity upon incubation at 55 degrees C suggested heat lability. An activation energy of 9.6 kcal/mol was calculated. The nature of the catalytic mechanism of the enzyme was investigated, and initial velocity studies showed linear converging patterns of double-reciprocal plots of the data, consistent with a sequential catalytic mechanism. The product inhibition pattern was at variance with both the ordered Bi-Bi and random mechanisms. The observed competition between purine and nucleoside, and between inorganic orthophosphate and ribose 1-phosphate for this ordered mechanism, suggest a Theorell-Chance mechanism. Michaelis constants determined for substrates of the enzyme were 4.35 X 10(-5) M for guanosine, 3.00 X 10(-5) M for guanine, and 2.15 X 10(-2) M for inorganic orthophosphate."}
{"id": "PMID:9973", "title": "Mung bean nuclease I. Physical, chemical, and catalytic properties.", "content": "A simplified purification procedure for mung bean nuclease has been developed yielding a stable enzyme that is homogeneous in regards to shape and size. The nuclease is a glycoprotein consisting of 29% carbohydrate by weight. It has a molecular weight of 39 000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme contains 1 sulfhydryl group and 3 disulfide bonds per molecule. It has a high content (12.6 mol %) of aromatic residues. Approximately 70% of the enzyme molecules contain a peptide bond cleavage at a single region in the protein. The two polypeptides, 25 000 and 15 000 daltons, are covalently linked by a disulfide bond(s). Both the cleaved and intact forms of the enzyme are equally active in the hydrolysis of the phosphate ester linkages in either DNA, RNA, or adenosine 3'-monophophate. The enzymatic activity of mung bean nuclease can be stabilized at pH 5 in the presence of 0.1 mM zinc acetate, 1.0 mM cysteine, and 0.001% Triton X-100. The enzyme can be inactivated and reactivated by the removal and readdition of Zn2+ or sulfhydryl compounds.", "contents": "Mung bean nuclease I. Physical, chemical, and catalytic properties. A simplified purification procedure for mung bean nuclease has been developed yielding a stable enzyme that is homogeneous in regards to shape and size. The nuclease is a glycoprotein consisting of 29% carbohydrate by weight. It has a molecular weight of 39 000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme contains 1 sulfhydryl group and 3 disulfide bonds per molecule. It has a high content (12.6 mol %) of aromatic residues. Approximately 70% of the enzyme molecules contain a peptide bond cleavage at a single region in the protein. The two polypeptides, 25 000 and 15 000 daltons, are covalently linked by a disulfide bond(s). Both the cleaved and intact forms of the enzyme are equally active in the hydrolysis of the phosphate ester linkages in either DNA, RNA, or adenosine 3'-monophophate. The enzymatic activity of mung bean nuclease can be stabilized at pH 5 in the presence of 0.1 mM zinc acetate, 1.0 mM cysteine, and 0.001% Triton X-100. The enzyme can be inactivated and reactivated by the removal and readdition of Zn2+ or sulfhydryl compounds."}
{"id": "PMID:9974", "title": "Mung bean nuclease I. Terminally directed hydrolysis of native DNA.", "content": "Under conditions which favor the duplex structure of DNA, mung bean nuclease catalyzes a limited number of double-strand cleavages (probably less than 50) in the interior of native T7 DNA. However, under conditions which are not as favorable to a tight helical structure, the large duplex polymers previously produced are completely degraded from their termini with a continuous accumulation of mono-, di-, and trinucleotides. The terminally directed activity is an intrinsic property of the enzyme molecule because (1) it is inactivated and reactivated in parallel with the single-strand activity and (2) the two activities coelectrophorese on analytical gels. Kinetic measurements indicate that the apparent Km for the terminally directed hydrolysis of native DNA is relatively high. The pH optimum for both the hydrolysis of denatured DNA and the terminally directed hydrolysis of native DNA becomes more acidic with increasing salt concentration. The relative preference for single-stranded structures increases as the pH becomes more basic.", "contents": "Mung bean nuclease I. Terminally directed hydrolysis of native DNA. Under conditions which favor the duplex structure of DNA, mung bean nuclease catalyzes a limited number of double-strand cleavages (probably less than 50) in the interior of native T7 DNA. However, under conditions which are not as favorable to a tight helical structure, the large duplex polymers previously produced are completely degraded from their termini with a continuous accumulation of mono-, di-, and trinucleotides. The terminally directed activity is an intrinsic property of the enzyme molecule because (1) it is inactivated and reactivated in parallel with the single-strand activity and (2) the two activities coelectrophorese on analytical gels. Kinetic measurements indicate that the apparent Km for the terminally directed hydrolysis of native DNA is relatively high. The pH optimum for both the hydrolysis of denatured DNA and the terminally directed hydrolysis of native DNA becomes more acidic with increasing salt concentration. The relative preference for single-stranded structures increases as the pH becomes more basic."}
{"id": "PMID:9975", "title": "Effects of iodination of tyrosyl residues on the binding and action of glucagon at its receptor.", "content": "The binding and action of glucagon at its receptor in hepatic plasma membranes have been compared, as a function of pH, with that of glucagon containing iodotyrosyl residues. Iodinated glucagon, at pH 7.0 and below, binds to the receptor and activates adenylate cyclase with an affinity about threefold higher than that of native glucagon. At pH 8.5, the affinity of the receptor for native glucagon is the same as that seen at pH 7.0. However, iodinated glucagon binds with a lowered affinity with increasing pH. The decreased affinity of the iodinated hormone correlates with ionization of the iodotyrosyl phenoxy groups, which has a pKa of 8.2. It is suggested that the decreased affinity is actually due to the inability of the ionized iodoglucagon to bind to the receptor. The relative potency of native and iodoglucagon will depend, therefore, on the concentrations of ionized and un-ionized species of iodoglucagon, which in turn depend on the pH of the medium. We conclude that incorporation of iodine atoms in the tyrosyl residues of glucagon has two major effects: (i) the iodine atom increases hydrophobic interaction of the hormone with the receptor and (ii) ionization of the phenoxy groups results in the loss of biological activity possibly as the result of loss of hydrogen bonding capability. Thus, the tyrosyl residues in glucagon are critically involved in the function of the hormone.", "contents": "Effects of iodination of tyrosyl residues on the binding and action of glucagon at its receptor. The binding and action of glucagon at its receptor in hepatic plasma membranes have been compared, as a function of pH, with that of glucagon containing iodotyrosyl residues. Iodinated glucagon, at pH 7.0 and below, binds to the receptor and activates adenylate cyclase with an affinity about threefold higher than that of native glucagon. At pH 8.5, the affinity of the receptor for native glucagon is the same as that seen at pH 7.0. However, iodinated glucagon binds with a lowered affinity with increasing pH. The decreased affinity of the iodinated hormone correlates with ionization of the iodotyrosyl phenoxy groups, which has a pKa of 8.2. It is suggested that the decreased affinity is actually due to the inability of the ionized iodoglucagon to bind to the receptor. The relative potency of native and iodoglucagon will depend, therefore, on the concentrations of ionized and un-ionized species of iodoglucagon, which in turn depend on the pH of the medium. We conclude that incorporation of iodine atoms in the tyrosyl residues of glucagon has two major effects: (i) the iodine atom increases hydrophobic interaction of the hormone with the receptor and (ii) ionization of the phenoxy groups results in the loss of biological activity possibly as the result of loss of hydrogen bonding capability. Thus, the tyrosyl residues in glucagon are critically involved in the function of the hormone."}
{"id": "PMID:9976", "title": "Steady state kinetic analysis of the mechanism of guanosine triphosphate hydrolysis catalyzed by Escherichia coli elongation factor G and the ribosome.", "content": "The mechanism of guanosine triphosphate (GTP) hydrolysis catalyzed by elongation factor G and the ribosome in the absence of other participants in protein synthesis was examined by steady-state kinetic analysis. Optimal hydrolytic conditions were determined to be approximately pH 8.0, 20 mM Mg2+, and 80 mM NH4+. Kinetic analyses were performed under these conditions at constant elongation factor G concentrations and variable ribosome and GTP concentrations. The resulting double-reciprocal plots in conjunction with the inhibition patterns obtained with GDP indicated that the reaction occurs by an ordered mechanism in which GTP is the leading obligatory substrate. Dissociation constants for GTP and guanosine diphosphate (GDP), as well as limiting Michaelis constants for GTP and ribosomes, were calculated from the double-reciprocal plots. These values are: KSGTP = 37.0 muM, KSGDP = 16.5 muKMGTP = 8.0 muM, KMR = 0.22 muM. Inhibition was also observed at high ribosomal concentrations and suggests that inhibition was due both to the decreased breakdown of the tertiary elongation factor G-GDP-ribosome posthydrolytic complex and to the formation of a nonproductive elongation factor G-ribosome complex. A sequential mechanism with a dead-end elongation factor G-ribosome complex has been constructed to describe the hydrolysis of GTP catalyzed by elongation factor G and the ribosome.", "contents": "Steady state kinetic analysis of the mechanism of guanosine triphosphate hydrolysis catalyzed by Escherichia coli elongation factor G and the ribosome. The mechanism of guanosine triphosphate (GTP) hydrolysis catalyzed by elongation factor G and the ribosome in the absence of other participants in protein synthesis was examined by steady-state kinetic analysis. Optimal hydrolytic conditions were determined to be approximately pH 8.0, 20 mM Mg2+, and 80 mM NH4+. Kinetic analyses were performed under these conditions at constant elongation factor G concentrations and variable ribosome and GTP concentrations. The resulting double-reciprocal plots in conjunction with the inhibition patterns obtained with GDP indicated that the reaction occurs by an ordered mechanism in which GTP is the leading obligatory substrate. Dissociation constants for GTP and guanosine diphosphate (GDP), as well as limiting Michaelis constants for GTP and ribosomes, were calculated from the double-reciprocal plots. These values are: KSGTP = 37.0 muM, KSGDP = 16.5 muKMGTP = 8.0 muM, KMR = 0.22 muM. Inhibition was also observed at high ribosomal concentrations and suggests that inhibition was due both to the decreased breakdown of the tertiary elongation factor G-GDP-ribosome posthydrolytic complex and to the formation of a nonproductive elongation factor G-ribosome complex. A sequential mechanism with a dead-end elongation factor G-ribosome complex has been constructed to describe the hydrolysis of GTP catalyzed by elongation factor G and the ribosome."}
{"id": "PMID:9977", "title": "Nuclear magnetic resonance determination of intramolecular distances in bovine pancreatic trypsin inhibitor using nitrotyrosine chelation of lanthanides.", "content": "Nitration of tyrosine has been investigated as a means for chemically introducing lanthanide chelating sites at known positions in proteins. The low-field portions of the 250-MHZ and 270-MHZ 1H nuclear magnetic resonance spectra of native and chemically modified bovine pancreatic trypsin inhibitor have been studied in the presence of lanthanide ions. Comparisons of spectral changes observed with native, mononitro (tryosine 10) and dinitro (tyrosines 10 and 21) derivatives enable these changes to be separately attributed to metal bound at nitrotyrosine 21, nitrotyrosine 10, or the set of five carboxyl groups. The pH dependence of Pr(III) and Eu(III) induced chemical shifts yields stability constants of 50 and 159 M-1 for the association between lanthanides and nitrotyrosines 10 and 21, respectively. Correlation times for the interactions with Gd(III) bound to specific nitrotyrosines are estimated from the induced line broadening of resonances of the nitrotyrosine ring protons. These stability constants and correlation times are used to determine the distances from the different metal binding sites to buried backbone NH protons having resolved resonances. Comparisons with distances in the x-ray crystal structure give assignments of the NH resonances to a small set of buried backbone NH's.", "contents": "Nuclear magnetic resonance determination of intramolecular distances in bovine pancreatic trypsin inhibitor using nitrotyrosine chelation of lanthanides. Nitration of tyrosine has been investigated as a means for chemically introducing lanthanide chelating sites at known positions in proteins. The low-field portions of the 250-MHZ and 270-MHZ 1H nuclear magnetic resonance spectra of native and chemically modified bovine pancreatic trypsin inhibitor have been studied in the presence of lanthanide ions. Comparisons of spectral changes observed with native, mononitro (tryosine 10) and dinitro (tyrosines 10 and 21) derivatives enable these changes to be separately attributed to metal bound at nitrotyrosine 21, nitrotyrosine 10, or the set of five carboxyl groups. The pH dependence of Pr(III) and Eu(III) induced chemical shifts yields stability constants of 50 and 159 M-1 for the association between lanthanides and nitrotyrosines 10 and 21, respectively. Correlation times for the interactions with Gd(III) bound to specific nitrotyrosines are estimated from the induced line broadening of resonances of the nitrotyrosine ring protons. These stability constants and correlation times are used to determine the distances from the different metal binding sites to buried backbone NH protons having resolved resonances. Comparisons with distances in the x-ray crystal structure give assignments of the NH resonances to a small set of buried backbone NH's."}
{"id": "PMID:9978", "title": "Existence of electrogenic hydrogen ion/sodium ion antiport in Halobacterium halobium cell envelope vesicles.", "content": "Illumination causes the extrusion of protons from Halobacterium halobium cell envelope vesicles, as a result of the action of light on bacteriorhodopsin. The protonmotive force developed is coupled to the active transport of Na+ out of the vesicles. The light-dependent ion fluxes in these vesicles were studied by following changes in the external pH, in the fluorescence of the dye, 3,3'-dipentyloxadicarbocyanine, in the 22Na content of the vesicles, and in [3H]dibenzyldimethylammonium (DDA+) accumulation. During Na+ efflux, and dependent on the presence of Na+ inside the vesicles, the initial light-induced H+ extrusion is followed by H+ influx, which results in net alkalinization of the medium at pH greater than 6.5. When the Na+ content of the vesicles is depleted, the original net of the medium is restored and large deltapH develops, accompanied by a decrease in the electrical potential. Data reported elsewhere suggest that the driving force for the transport of some amino acids consists mainly of the electrical potential, while for others it comprises the Na+ gradient as well. Glutamate transport appears to be energized only by the Na+ gradient. The development of the Na+ gradient during illumination thus plays an important role in energy coupling. The results obtained are consistent with the existence of an electrogenic H+/Na+ antiport mechanism (H+/Na+ greater than 1) in H halobium which facilitates the uphill Na+ efflux. The light-induced protonmotive force thereby becomes the driving force in forming a Na+ gradient. The presence of the proposed H+/Na+ antiporter explains many of the light-induced pH effects in intact H. halobium cells.", "contents": "Existence of electrogenic hydrogen ion/sodium ion antiport in Halobacterium halobium cell envelope vesicles. Illumination causes the extrusion of protons from Halobacterium halobium cell envelope vesicles, as a result of the action of light on bacteriorhodopsin. The protonmotive force developed is coupled to the active transport of Na+ out of the vesicles. The light-dependent ion fluxes in these vesicles were studied by following changes in the external pH, in the fluorescence of the dye, 3,3'-dipentyloxadicarbocyanine, in the 22Na content of the vesicles, and in [3H]dibenzyldimethylammonium (DDA+) accumulation. During Na+ efflux, and dependent on the presence of Na+ inside the vesicles, the initial light-induced H+ extrusion is followed by H+ influx, which results in net alkalinization of the medium at pH greater than 6.5. When the Na+ content of the vesicles is depleted, the original net of the medium is restored and large deltapH develops, accompanied by a decrease in the electrical potential. Data reported elsewhere suggest that the driving force for the transport of some amino acids consists mainly of the electrical potential, while for others it comprises the Na+ gradient as well. Glutamate transport appears to be energized only by the Na+ gradient. The development of the Na+ gradient during illumination thus plays an important role in energy coupling. The results obtained are consistent with the existence of an electrogenic H+/Na+ antiport mechanism (H+/Na+ greater than 1) in H halobium which facilitates the uphill Na+ efflux. The light-induced protonmotive force thereby becomes the driving force in forming a Na+ gradient. The presence of the proposed H+/Na+ antiporter explains many of the light-induced pH effects in intact H. halobium cells."}
{"id": "PMID:9979", "title": "Fractionation of DNA from mammalian cells by alkaline elution.", "content": "The method of alkaline elution provides a sensitive measure of DNA single-strand length distribution in mamalian cells and is applicable to a variety of problems concerning DNA damage, repair, and replication. The physical basis of the elution process was studied. The kinetics of elution above the alkaline transition pH were found to occur in two phases: an initial phase in which single-strand length is rate limiting, followed by a phase in which elution is accelerated due to the accumulation of alkali-induced strand breaks. The range of DNA single-strand lengths that can be discriminated by elution above the alkaline transition pH was estimated by calibration relative to the effects of x ray, and was found to be 5 X 10(8)-10(10) daltons. Shorter DNA strands elute within the pH transition zone, which extended from pH 11.3 to 11.7 when tetrapropylammonium hydroxide was used as base. This elution was relatively rapid, but was sharply limited by pH, according to the length of the strands: the length of the strands eluted increased with increasing pH. Alkaline elution was inhibited by treatment of cells with low concentrations of nitrogen mustard, a bifunctional alkylating known to cross-link DNA. On investigation of the possibility that DNA subclasses may differ in their elution behavior, satellite L strands were found to elute more slowly from cells exposed to a low dose of x ray than did the bulk DNA.", "contents": "Fractionation of DNA from mammalian cells by alkaline elution. The method of alkaline elution provides a sensitive measure of DNA single-strand length distribution in mamalian cells and is applicable to a variety of problems concerning DNA damage, repair, and replication. The physical basis of the elution process was studied. The kinetics of elution above the alkaline transition pH were found to occur in two phases: an initial phase in which single-strand length is rate limiting, followed by a phase in which elution is accelerated due to the accumulation of alkali-induced strand breaks. The range of DNA single-strand lengths that can be discriminated by elution above the alkaline transition pH was estimated by calibration relative to the effects of x ray, and was found to be 5 X 10(8)-10(10) daltons. Shorter DNA strands elute within the pH transition zone, which extended from pH 11.3 to 11.7 when tetrapropylammonium hydroxide was used as base. This elution was relatively rapid, but was sharply limited by pH, according to the length of the strands: the length of the strands eluted increased with increasing pH. Alkaline elution was inhibited by treatment of cells with low concentrations of nitrogen mustard, a bifunctional alkylating known to cross-link DNA. On investigation of the possibility that DNA subclasses may differ in their elution behavior, satellite L strands were found to elute more slowly from cells exposed to a low dose of x ray than did the bulk DNA."}
{"id": "PMID:9980", "title": "Polymerization pattern of insulin at pH 7.0.", "content": "Sedimentation equilibrium results, obtained with bovine zinc-free insulin (with and without a component of proinsulin) at pH 7.0, I o.2, 25 degrees C, and up to a total concentration of 0.8 g/l., are shown to be consistent with three different polymerization patterns, all involving an isodesmic indefinite self-association of specified oligomeric species. The analysis procedure, based on closed solutions formed by summing infinite series, yields for each pattern a set of equilibrium constants, It is shown that a distinction between the possible patterns can be made by analyzing sedimentation equilibrium results obtained in a higher total concentration range (up to 4 g/1.) with insulin freed of zinc and proinsulin, account being taken of the composition dependence of activity coefficients. The favored pattern, which differs from that previously reported in the literature, involves the dimerization of monomeric insulin (mol wt 5734), governed by a dimerization constant of 11 X 10(4) M-1 and the isodesmic indefinite self-association of the dimer, described by an association constant of 1.7 X 10(4) M-1. This polymerization pattern is also shown to be consistent with the reaction boundary observed in sedimentation velocity experiments.", "contents": "Polymerization pattern of insulin at pH 7.0. Sedimentation equilibrium results, obtained with bovine zinc-free insulin (with and without a component of proinsulin) at pH 7.0, I o.2, 25 degrees C, and up to a total concentration of 0.8 g/l., are shown to be consistent with three different polymerization patterns, all involving an isodesmic indefinite self-association of specified oligomeric species. The analysis procedure, based on closed solutions formed by summing infinite series, yields for each pattern a set of equilibrium constants, It is shown that a distinction between the possible patterns can be made by analyzing sedimentation equilibrium results obtained in a higher total concentration range (up to 4 g/1.) with insulin freed of zinc and proinsulin, account being taken of the composition dependence of activity coefficients. The favored pattern, which differs from that previously reported in the literature, involves the dimerization of monomeric insulin (mol wt 5734), governed by a dimerization constant of 11 X 10(4) M-1 and the isodesmic indefinite self-association of the dimer, described by an association constant of 1.7 X 10(4) M-1. This polymerization pattern is also shown to be consistent with the reaction boundary observed in sedimentation velocity experiments."}
{"id": "PMID:9981", "title": "Double-ternary complex affinity chromatography: preparation of alcohol dehydrogenases.", "content": "A general affinity chromatographic method for alcohol dehydrogenase purification has been developed by employing immobilized 4-substituted pyrazole derivatives that isolate the enzyme through formation of a specific ternary complex. Sepharose 4B is activated with 300 mg of cyanogen bromide/ml of packed gel and coupled to 4-[3-(N-6-aminocaproyl)aminopropyl]pyrazole. From crude liver extracts in 50 mM phosphate-0.37 mM nicotinamide adenine dinucleotide, pH 7.5, alcohol dehydrogenase is optimally bound at a capacity of 4-5 mg of enzyme/ml of gel. Addition of ethanol, propanol, or butanol, 500 mM, results in the formation of a second ternary complex, which allows the elution of bound enzyme in high yield and purity. This double-ternary complex affinity chromatography has been applied successfully to human, horse, rat, and rabbit liver extracts to isolate the respective homogeneous alcohol dehydrogenases.", "contents": "Double-ternary complex affinity chromatography: preparation of alcohol dehydrogenases. A general affinity chromatographic method for alcohol dehydrogenase purification has been developed by employing immobilized 4-substituted pyrazole derivatives that isolate the enzyme through formation of a specific ternary complex. Sepharose 4B is activated with 300 mg of cyanogen bromide/ml of packed gel and coupled to 4-[3-(N-6-aminocaproyl)aminopropyl]pyrazole. From crude liver extracts in 50 mM phosphate-0.37 mM nicotinamide adenine dinucleotide, pH 7.5, alcohol dehydrogenase is optimally bound at a capacity of 4-5 mg of enzyme/ml of gel. Addition of ethanol, propanol, or butanol, 500 mM, results in the formation of a second ternary complex, which allows the elution of bound enzyme in high yield and purity. This double-ternary complex affinity chromatography has been applied successfully to human, horse, rat, and rabbit liver extracts to isolate the respective homogeneous alcohol dehydrogenases."}
{"id": "PMID:9982", "title": "Human liver alcohol dehydrogenase: purification, composition, and catalytic features.", "content": "Alcohol dehydrogenase has been purified from human liver by affinity chromatography. Ultracentrifugation, Sephadex G-200 chromatography, and amino acid analyses of multiple preparations demonstrate homogeneity of molecular weight. Sodium dodecyl sulfate disc gel electrophoresis reveals a single species of molecular weight 42 000. Based on a molecular weight of 85 000 for the dimer obtained from the amino acid composition and a molar absorptivity of A280nm0.1% = 0.58, the enzyme contains 3.6-4.2 g-atoms of zinc, as determined by emission spectrography, microwave-induced emission, and atomic absorption spectrometry. Inhibition by o-phenanthroline, (ethylenedinitrilo)tetraacetic acid, and alpha,alpha'-bipyridine demonstrates that zinc is essential to enzymatic function. Detailed kinetic analyses using primary alcohols of the homologous series CH3(CH2)nOH, n = 0-5, and the corresponding aldehydes as substrates show that KM values become smaller as n increases. This suggest that hydrophobic interactions play a role in substrate binding. The availability of well-defined preparations of human liver alcohol dehydrogenase now allows definitive genetic and functional studies of this enzyme to elucidate human ethanol metabolism.", "contents": "Human liver alcohol dehydrogenase: purification, composition, and catalytic features. Alcohol dehydrogenase has been purified from human liver by affinity chromatography. Ultracentrifugation, Sephadex G-200 chromatography, and amino acid analyses of multiple preparations demonstrate homogeneity of molecular weight. Sodium dodecyl sulfate disc gel electrophoresis reveals a single species of molecular weight 42 000. Based on a molecular weight of 85 000 for the dimer obtained from the amino acid composition and a molar absorptivity of A280nm0.1% = 0.58, the enzyme contains 3.6-4.2 g-atoms of zinc, as determined by emission spectrography, microwave-induced emission, and atomic absorption spectrometry. Inhibition by o-phenanthroline, (ethylenedinitrilo)tetraacetic acid, and alpha,alpha'-bipyridine demonstrates that zinc is essential to enzymatic function. Detailed kinetic analyses using primary alcohols of the homologous series CH3(CH2)nOH, n = 0-5, and the corresponding aldehydes as substrates show that KM values become smaller as n increases. This suggest that hydrophobic interactions play a role in substrate binding. The availability of well-defined preparations of human liver alcohol dehydrogenase now allows definitive genetic and functional studies of this enzyme to elucidate human ethanol metabolism."}
{"id": "PMID:9983", "title": "Regulatory properties of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa. Kinetic studies and fluorescence titration.", "content": "Mechanisms involved in the action of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa (EC 1.6.1.1) have been investigated by means of kinetic studies and fluorescence titration. Our results, as well as those from previous investigations, suggest that the allosteric MWC model (Monod, J., Wyman, J., and Changeux, J. P. (1965), J. Mol. Biol. 12, 88-118) may be used as a first step for the explanation of the properties of the transhydrogenase. The basic reaction of the enzyme is the oxidation of reduced triphosphopyridine nucleotide (TPNH) by diphosphopyridine nucleotide (DPN+). In terms of the model, the functional R state is favored by TPNH, whereas the product triphosphopyridine nucleotide (TPN+) behaves as an allosteric inhibitor, and is therefore assumed to favor the nonfunctional T state. To a slight extent, the T state is also favored by inorganic phosphate. On the other hand, adenosine 2'-monophosphate and several other 2'-phosphate nucleotides function as activators, and hence are presumed to shift the allosteric equilibrium toward the R state. The studies in this paper suggest a specific regulatory site for the transhydrogenase.", "contents": "Regulatory properties of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa. Kinetic studies and fluorescence titration. Mechanisms involved in the action of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa (EC 1.6.1.1) have been investigated by means of kinetic studies and fluorescence titration. Our results, as well as those from previous investigations, suggest that the allosteric MWC model (Monod, J., Wyman, J., and Changeux, J. P. (1965), J. Mol. Biol. 12, 88-118) may be used as a first step for the explanation of the properties of the transhydrogenase. The basic reaction of the enzyme is the oxidation of reduced triphosphopyridine nucleotide (TPNH) by diphosphopyridine nucleotide (DPN+). In terms of the model, the functional R state is favored by TPNH, whereas the product triphosphopyridine nucleotide (TPN+) behaves as an allosteric inhibitor, and is therefore assumed to favor the nonfunctional T state. To a slight extent, the T state is also favored by inorganic phosphate. On the other hand, adenosine 2'-monophosphate and several other 2'-phosphate nucleotides function as activators, and hence are presumed to shift the allosteric equilibrium toward the R state. The studies in this paper suggest a specific regulatory site for the transhydrogenase."}
{"id": "PMID:9984", "title": "Regulatory properties of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa. Active enzyme ultracentrifugation studies.", "content": "Active enzyme ultracentrifugation studies of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa (EC 1.6.1.1.) show that the enzymatic reaction is catalyzed by a molecular species characterized by an S20,W value of about 34 S, whatever the reduced substrate may be (tri- or diphosphopyridine nucleotide). The filamentous aggregated form of the enzyme (S20,W = 121 S and higher), identified by previous investigations (Cohen, P. T., and Kaplan, N. O. (1970), J. Biol. Chem. 245, 2825-2836; Louie, D. D., Kaplan, N. O., and Mc Lean, J. D. (1972), J. Mol. Biol. 70, 651-664), appears, therefore, to be an inactive species. The physiological implications of the enzyme are discussed. Several lines of evidence lead to the conclusion that the transhydrogenase might act as an essential link between carbohydrate catabolism and the respiratory chain.", "contents": "Regulatory properties of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa. Active enzyme ultracentrifugation studies. Active enzyme ultracentrifugation studies of the pyridine nucleotide transhydrogenase from Pseudomonas aeruginosa (EC 1.6.1.1.) show that the enzymatic reaction is catalyzed by a molecular species characterized by an S20,W value of about 34 S, whatever the reduced substrate may be (tri- or diphosphopyridine nucleotide). The filamentous aggregated form of the enzyme (S20,W = 121 S and higher), identified by previous investigations (Cohen, P. T., and Kaplan, N. O. (1970), J. Biol. Chem. 245, 2825-2836; Louie, D. D., Kaplan, N. O., and Mc Lean, J. D. (1972), J. Mol. Biol. 70, 651-664), appears, therefore, to be an inactive species. The physiological implications of the enzyme are discussed. Several lines of evidence lead to the conclusion that the transhydrogenase might act as an essential link between carbohydrate catabolism and the respiratory chain."}
{"id": "PMID:9985", "title": "Coenzyme binding by triphosphopyridine nucleotide dependent isocitrate dehydrogenase from beef liver. Equilibrium and kinetics studies.", "content": "The binding of reduced nicotinamide adenine dinucleotide phosphate (NADPH) to nicotinamide adenine dinucleotide phosphate (NADP) dependent isocitrate dehydrogenase from beef liver cytoplasm was studied by several equilibrium techniques (ultracentrifugation, molecular sieving, ultrafiltration, fluorescence). Two binding sites (per dimeric enzyme molecule) were found with slightly different dissociation constants (0.5 and 0.12 muM) and fluorescence yields (7.7 and 6.3). A ternary complex was formed between enzyme, isocitrate, and NADPH, in which NADPH dissociation constant was 5 muM. On the contrary, no binding of NADPH to the enzyme took place in the presence of magnesium isocitrate. Dialysis experiments showed the existence of 1 NADP binding site/dimer, with a dissociation constant of 26 muM. When NADPH was present with the enzyme in the proportion of 1 molecule/dimer, the dissociation constant of NADP was decreased fourfold, reaching a value quantitatively comparable to the Michaelis constant. The kinetics of coenzyme binding was followed using the stopped-flow technique with fluorescence detection. NADPH binding to the enzyme occurred through one fast reaction (k1 = 20 muM-1 s-1). Dissociation of NADPH took place upon NADP binding; however, equilibrium as well as kinetic data were incompatible with a simple competition scheme. Dissociation of NADPH from the enzyme upon magnesium isocitrate binding was preceded by the formation of a transitory ternary complex in which the fluorescence of NADPH was only about 30% of that in the enzyme-NADPH complex. Then interaction between the conenzymes and the involvement of ternary complexes in the catalytic mechanism are discussed in relation with what is known about the regulatory role of the coenzyme (Carlier, M. F., and Pantaloni, D. (1976), Biochemistry, 15, 1761-1766).", "contents": "Coenzyme binding by triphosphopyridine nucleotide dependent isocitrate dehydrogenase from beef liver. Equilibrium and kinetics studies. The binding of reduced nicotinamide adenine dinucleotide phosphate (NADPH) to nicotinamide adenine dinucleotide phosphate (NADP) dependent isocitrate dehydrogenase from beef liver cytoplasm was studied by several equilibrium techniques (ultracentrifugation, molecular sieving, ultrafiltration, fluorescence). Two binding sites (per dimeric enzyme molecule) were found with slightly different dissociation constants (0.5 and 0.12 muM) and fluorescence yields (7.7 and 6.3). A ternary complex was formed between enzyme, isocitrate, and NADPH, in which NADPH dissociation constant was 5 muM. On the contrary, no binding of NADPH to the enzyme took place in the presence of magnesium isocitrate. Dialysis experiments showed the existence of 1 NADP binding site/dimer, with a dissociation constant of 26 muM. When NADPH was present with the enzyme in the proportion of 1 molecule/dimer, the dissociation constant of NADP was decreased fourfold, reaching a value quantitatively comparable to the Michaelis constant. The kinetics of coenzyme binding was followed using the stopped-flow technique with fluorescence detection. NADPH binding to the enzyme occurred through one fast reaction (k1 = 20 muM-1 s-1). Dissociation of NADPH took place upon NADP binding; however, equilibrium as well as kinetic data were incompatible with a simple competition scheme. Dissociation of NADPH from the enzyme upon magnesium isocitrate binding was preceded by the formation of a transitory ternary complex in which the fluorescence of NADPH was only about 30% of that in the enzyme-NADPH complex. Then interaction between the conenzymes and the involvement of ternary complexes in the catalytic mechanism are discussed in relation with what is known about the regulatory role of the coenzyme (Carlier, M. F., and Pantaloni, D. (1976), Biochemistry, 15, 1761-1766)."}
{"id": "PMID:9986", "title": "Oxidation-reduction potential measurements on chloroperoxidase and its complexes.", "content": "The oxidation-reduction potential of chloroperoxidase, an enzyme which catalyzes peroxidative chlorination, bromination, and iodination reactions, has been investigated. In addition to catalyzing biological halogenation reactions, chloroperoxidase is unusual in that the carbon monoxide complex of ferrous chloroperoxidase shows the typical long wavelength Soret absorption associated with P-450 hemoproteins. The pH dependence of the chloroperoxidase oxidation-reduction potential shows a discontinuity around pH 4.7. Similarly, measurements of the affinity of ferrous chloroperoxidase for carbon monoxide monitored both by spectroscopic and potentiometric titration exhibit a discontinuity in the pH 4.7 region. Oxidation-reduction potential measurements on chloroperoxidase in a CO atmosphere also show a discontinuous pH profile. These results suggest that ferrous chloroperoxidase undergoes reversible modification at low pH and that these changes are reflected in the oxidation-reduction potential. The oxidation-reduction potential of chloroperoxidase at pH 6.9 is - 140 mV, close to that measured for cytochrome P-450cam in the presence of substrate. The oxidation-reduction potential of chloroperoxidase at pH 2.7, the pH optimum for enzymatic chlorination, is +150 mV. The oxidation-reduction potentials of the halide complexes of chloroperoxidase (chloride, bromide, and iodide) are essentially identical with the potential measurements on the native enzyme. These observations suggest that, although halide anions bind to the enzyme, they probably do not bind as an axial ligand to the heme ferric iron.", "contents": "Oxidation-reduction potential measurements on chloroperoxidase and its complexes. The oxidation-reduction potential of chloroperoxidase, an enzyme which catalyzes peroxidative chlorination, bromination, and iodination reactions, has been investigated. In addition to catalyzing biological halogenation reactions, chloroperoxidase is unusual in that the carbon monoxide complex of ferrous chloroperoxidase shows the typical long wavelength Soret absorption associated with P-450 hemoproteins. The pH dependence of the chloroperoxidase oxidation-reduction potential shows a discontinuity around pH 4.7. Similarly, measurements of the affinity of ferrous chloroperoxidase for carbon monoxide monitored both by spectroscopic and potentiometric titration exhibit a discontinuity in the pH 4.7 region. Oxidation-reduction potential measurements on chloroperoxidase in a CO atmosphere also show a discontinuous pH profile. These results suggest that ferrous chloroperoxidase undergoes reversible modification at low pH and that these changes are reflected in the oxidation-reduction potential. The oxidation-reduction potential of chloroperoxidase at pH 6.9 is - 140 mV, close to that measured for cytochrome P-450cam in the presence of substrate. The oxidation-reduction potential of chloroperoxidase at pH 2.7, the pH optimum for enzymatic chlorination, is +150 mV. The oxidation-reduction potentials of the halide complexes of chloroperoxidase (chloride, bromide, and iodide) are essentially identical with the potential measurements on the native enzyme. These observations suggest that, although halide anions bind to the enzyme, they probably do not bind as an axial ligand to the heme ferric iron."}
{"id": "PMID:9987", "title": "The influence of postnatal nutritional deprivation on the phospholipid content of developing rat lung.", "content": "It has been previously reported that fasting may result in decreased lung surfactant production. In order to investigate this relationship and the role of nutrition in lung phospholipid synthesis, 21-day-old rats were exposed for 60 h to one of five dietary regimens: standard rat chow (controls), fasting, pure glucose, pure fat, or pure protein. After the period of fasting there was a 33% decrease in lung protein content, but there was no change in DNA content. Exposure to any of the experimental diets resulted in a decrease in tissue total phospholipid and phosphatidylcholine content per lung, but not per unit lung protein. Similarly lung lavage phospholipid and phosphatidylcholine content was decreased by 25% after fasting when expressed per lung or per unit DNA, but not per unit protein. Pulmonary cholinephosphotransferase (EC 2.7.8.2) activity was decreased in the fasted animals and those fed the protein diet, but not in the glucose or fat-fed animals. The activities of acetyl-CoA carboxylase (EC 6.4.1.2) and microsomal fatty acid elongation were decreased in all the experimental groups except for the  glucose-fed group. It is concluded that fasting results in a decrease in lung cell size but not in lung cell number. Total phospholipid and phosphatidylcholine content in lung tissue and lung lavage is decreased per cell but not per unit cell mass.", "contents": "The influence of postnatal nutritional deprivation on the phospholipid content of developing rat lung. It has been previously reported that fasting may result in decreased lung surfactant production. In order to investigate this relationship and the role of nutrition in lung phospholipid synthesis, 21-day-old rats were exposed for 60 h to one of five dietary regimens: standard rat chow (controls), fasting, pure glucose, pure fat, or pure protein. After the period of fasting there was a 33% decrease in lung protein content, but there was no change in DNA content. Exposure to any of the experimental diets resulted in a decrease in tissue total phospholipid and phosphatidylcholine content per lung, but not per unit lung protein. Similarly lung lavage phospholipid and phosphatidylcholine content was decreased by 25% after fasting when expressed per lung or per unit DNA, but not per unit protein. Pulmonary cholinephosphotransferase (EC 2.7.8.2) activity was decreased in the fasted animals and those fed the protein diet, but not in the glucose or fat-fed animals. The activities of acetyl-CoA carboxylase (EC 6.4.1.2) and microsomal fatty acid elongation were decreased in all the experimental groups except for the  glucose-fed group. It is concluded that fasting results in a decrease in lung cell size but not in lung cell number. Total phospholipid and phosphatidylcholine content in lung tissue and lung lavage is decreased per cell but not per unit cell mass."}
{"id": "PMID:9988", "title": "Regulatory control and function of alanine dehydrogenase from a thermophilic bacillus.", "content": "L-alanine dehydrogenase, (L-alanine:NAD+ oxidoreductase (deaminating), EC 1.4.1.1) synthesis in a thermophilic bacillus was found to be subjected to regulatory control. Addition of L- and D-alanine and L-serine to cultures growing in the presence of either succinate or pyruvate, induced an accelerated synthesis of the alanine dehydrogenase enzyme. Synthesis of the enzyme was dependent on the presence of inducer during growth and was arrested by addition of glucose. Catabolite repression by glucose was abolished by limiting the ammonium concentration during growth. The apparent Km values of the substrates involved in alanine dehydrogenase activity are as follows (M): NH4+, 4-10(-2); pyruvate, 5-10(-4); NADH, 6-10(-5); L-alanine, 3.1-10(-3) and NAD, 2-10(-4). Alanine dehydrogenase activity was measurable at temperatures below the minimal growth temperature (at 25 degrees C) and the highest activity was found at 65 degrees C; heat denaturation occurred at 80 degrees C.", "contents": "Regulatory control and function of alanine dehydrogenase from a thermophilic bacillus. L-alanine dehydrogenase, (L-alanine:NAD+ oxidoreductase (deaminating), EC 1.4.1.1) synthesis in a thermophilic bacillus was found to be subjected to regulatory control. Addition of L- and D-alanine and L-serine to cultures growing in the presence of either succinate or pyruvate, induced an accelerated synthesis of the alanine dehydrogenase enzyme. Synthesis of the enzyme was dependent on the presence of inducer during growth and was arrested by addition of glucose. Catabolite repression by glucose was abolished by limiting the ammonium concentration during growth. The apparent Km values of the substrates involved in alanine dehydrogenase activity are as follows (M): NH4+, 4-10(-2); pyruvate, 5-10(-4); NADH, 6-10(-5); L-alanine, 3.1-10(-3) and NAD, 2-10(-4). Alanine dehydrogenase activity was measurable at temperatures below the minimal growth temperature (at 25 degrees C) and the highest activity was found at 65 degrees C; heat denaturation occurred at 80 degrees C."}
{"id": "PMID:9989", "title": "Studies on phenylalanine and tyrosine hydroxylation by rat brain tyrosine hydroxylase.", "content": "Tyrosine hydroxylase (EC1.14.16.2), presumably the rate-limiting enzyme in the biosynthesis of catecholamines, is known to catalyze the hydroxylation of both phenylalanine and tyrosine. Using both an isolated enzyme preparation and a synaptosomal preparation, where some architectural integrity of the tissue has been preserved, we have attempted to evaluate the manner in which these two substrates are hydroxylated by rat brain tyrosine hydroxylase. In the presence of tetrahydrobiopterin the isolated enzyme catalyzes the hydroxylation of phenylalanine to 3,4-dihydroxyphenylalanine with the release of free tyrosine as an obligatory intermediate. In contrast, the rat brain striatal synaptosomal preparation in the presence of endogenous cofactor converts phenylalanine to 3,4-dihydroxyphenylalanine without the release of free tyrosine.", "contents": "Studies on phenylalanine and tyrosine hydroxylation by rat brain tyrosine hydroxylase. Tyrosine hydroxylase (EC1.14.16.2), presumably the rate-limiting enzyme in the biosynthesis of catecholamines, is known to catalyze the hydroxylation of both phenylalanine and tyrosine. Using both an isolated enzyme preparation and a synaptosomal preparation, where some architectural integrity of the tissue has been preserved, we have attempted to evaluate the manner in which these two substrates are hydroxylated by rat brain tyrosine hydroxylase. In the presence of tetrahydrobiopterin the isolated enzyme catalyzes the hydroxylation of phenylalanine to 3,4-dihydroxyphenylalanine with the release of free tyrosine as an obligatory intermediate. In contrast, the rat brain striatal synaptosomal preparation in the presence of endogenous cofactor converts phenylalanine to 3,4-dihydroxyphenylalanine without the release of free tyrosine."}
{"id": "PMID:9990", "title": "Kinetic studies of Rhus vernicifera laccase. Role of the metal centers in electron transfer.", "content": "The reactions of Rhus vernicifera (monophenol,dihydroxyphenylalanine: oxygen oxidoreductase, EC 1.14.18.1) with the reducing substrates hydroquinone and ascorbic acid have been investigated with the stopped-flow technique. Rhus laccase appears to be present in two molecular forms with a pH-sensitive equilibrium constant regulating the relative concentrations of each species. A model for the reaction of Rhus laccase with reducing substrates has been formulated. The model is similar to one formulated earlier for the anaerobic reduction of laccase from Polyporus versicolor (Andr\u00e9asson, L.-E., Malstr\u00f6m, B.G., Str\u00f6mberg, C. and V\u00e4nng\u00e5rd, T. (1973) Eur. J. Biochem. 34, 434-439) and accounts for the reduction also of this enzyme. The essentials of the model are as follows: Electrons are taken up from reductants one at a time. The type 1 Cu2+ has a central role in mediating the transfer of at least one of the electrons needed for the reduction of the co-operative two-electron acceptor. Intramolecular reactions determine the concentrations of two molecular forms of the enzyme and influence the rate of reduction of the two-electron acceptor. The model, which has been used for successful simulations of the anaerobic reduction of Rhus laccase, is capable of explaining the reduction of laccases also in the presence of the inhibitor F-. In addition, the model gives an explanation of the behaviour of the laccases when reducing substrates and O2 are simultaneously present and is consistent with earlier observations of the post-steady-state reduction of the type 1 Cu2+ and the two-electron accetor (Holwerda, R.A. and Gray, H.B. (1974) J. Am. Chem. Soc. 96, 6008-6022).", "contents": "Kinetic studies of Rhus vernicifera laccase. Role of the metal centers in electron transfer. The reactions of Rhus vernicifera (monophenol,dihydroxyphenylalanine: oxygen oxidoreductase, EC 1.14.18.1) with the reducing substrates hydroquinone and ascorbic acid have been investigated with the stopped-flow technique. Rhus laccase appears to be present in two molecular forms with a pH-sensitive equilibrium constant regulating the relative concentrations of each species. A model for the reaction of Rhus laccase with reducing substrates has been formulated. The model is similar to one formulated earlier for the anaerobic reduction of laccase from Polyporus versicolor (Andr\u00e9asson, L.-E., Malstr\u00f6m, B.G., Str\u00f6mberg, C. and V\u00e4nng\u00e5rd, T. (1973) Eur. J. Biochem. 34, 434-439) and accounts for the reduction also of this enzyme. The essentials of the model are as follows: Electrons are taken up from reductants one at a time. The type 1 Cu2+ has a central role in mediating the transfer of at least one of the electrons needed for the reduction of the co-operative two-electron acceptor. Intramolecular reactions determine the concentrations of two molecular forms of the enzyme and influence the rate of reduction of the two-electron acceptor. The model, which has been used for successful simulations of the anaerobic reduction of Rhus laccase, is capable of explaining the reduction of laccases also in the presence of the inhibitor F-. In addition, the model gives an explanation of the behaviour of the laccases when reducing substrates and O2 are simultaneously present and is consistent with earlier observations of the post-steady-state reduction of the type 1 Cu2+ and the two-electron accetor (Holwerda, R.A. and Gray, H.B. (1974) J. Am. Chem. Soc. 96, 6008-6022)."}
{"id": "PMID:9991", "title": "Evidence for sulfhydryl groups at the active site of catechol-O-methyltransferase.", "content": "Earlier studies using affinity labeling reagents have suggested the existence of two nucleophilic groups at the active site of catechol-O-methyltransferase (S-adenosyl-L-methionine:catechol O-methyltransferase, EC 2.1.1.6). Both nucleophilic residues are critical for catalytic activity. In an effort to elucidate the nature of these residues and to further characterize the relationship between the chemical structure and the catalytic function of this enzyme, inactivation studies using N-ethylmaleimide were undertaken. Inactivation of the enzyme by N-ethylmaleimide under pseudo first-order conditions exhibited a non-linear relationship between the log of the fraction of enzyme activity remaining and preincubation time. Kinetic analysis of this inactivation process suggested the modification by N-ethylmaleimide of two residues at the active site of the enzyme, both crucial for catalytic activity. Detailed analysis of the inactivation process including substrate protection studies, pH profiles of inactivation, and incorporation studies using N-ethyl[2,3-14C2]maleimide provided additional evidence to support this conclusion.", "contents": "Evidence for sulfhydryl groups at the active site of catechol-O-methyltransferase. Earlier studies using affinity labeling reagents have suggested the existence of two nucleophilic groups at the active site of catechol-O-methyltransferase (S-adenosyl-L-methionine:catechol O-methyltransferase, EC 2.1.1.6). Both nucleophilic residues are critical for catalytic activity. In an effort to elucidate the nature of these residues and to further characterize the relationship between the chemical structure and the catalytic function of this enzyme, inactivation studies using N-ethylmaleimide were undertaken. Inactivation of the enzyme by N-ethylmaleimide under pseudo first-order conditions exhibited a non-linear relationship between the log of the fraction of enzyme activity remaining and preincubation time. Kinetic analysis of this inactivation process suggested the modification by N-ethylmaleimide of two residues at the active site of the enzyme, both crucial for catalytic activity. Detailed analysis of the inactivation process including substrate protection studies, pH profiles of inactivation, and incorporation studies using N-ethyl[2,3-14C2]maleimide provided additional evidence to support this conclusion."}
{"id": "PMID:9992", "title": "Microheterogeneity of arylsulfatase A from human tissues.", "content": "Human arylsulfatase A (cerebroside-3-sulfate 3-sulfohydrolase, EC 3.1.6.8) exhibited microheterogeneity on isoelectric focusing in polyacrylamide gels. Pure urinary enzyme gave 3 bands of activity with pI values of 4.7, 4.8 and 4.9, whereas purified liver enzyme yielded six equally spaced bands from pI 4.4 to 4.9. Detection of enzyme in the gel was made by either methylumbelliferyl sulfate or nitrocatechol sulfate. Crude enzyme preparations from human liver, kindey, placenta, brain and testis showed the six-banded pattern with varying amounts of activity in the different bands. The banding pattern of cultured human fibroblast extracts was distinctive: in addition to activity in the area of Bands 1-6 a sharp band at pI 5.1 was observed with both enzyme stains. This latter band was also present in metachromatic leukodystrophy fibroblast extracts. However, in this case the band did not appear when the specific aryl-sulfatase A stain was used. Enzyme Bands 1, 2 and 3 from urine were isolated by extraction of the gel. The three bands refocused in their initial positions; showed nearly identical enzymatic activities toward methylumbelliferyl sulfate, mitrocatechol sulfate, cerebroside sulfate and ascorbic acid 2-sulfate; and demonstrated equivalent immunological competence by antibody titration. The banding pattern of urinary arylsulfatase A was unchanged with neuraminidase treatment, whereas Bands 4-6 of the liver enzyme were converted to Bands 1-3 by this treatment. It appears that Bands 4-6 are due to sialylation of aryl-sulfatase A but that Bands 1-3 are probably due to some other type of post-ribosomal protein modification.", "contents": "Microheterogeneity of arylsulfatase A from human tissues. Human arylsulfatase A (cerebroside-3-sulfate 3-sulfohydrolase, EC 3.1.6.8) exhibited microheterogeneity on isoelectric focusing in polyacrylamide gels. Pure urinary enzyme gave 3 bands of activity with pI values of 4.7, 4.8 and 4.9, whereas purified liver enzyme yielded six equally spaced bands from pI 4.4 to 4.9. Detection of enzyme in the gel was made by either methylumbelliferyl sulfate or nitrocatechol sulfate. Crude enzyme preparations from human liver, kindey, placenta, brain and testis showed the six-banded pattern with varying amounts of activity in the different bands. The banding pattern of cultured human fibroblast extracts was distinctive: in addition to activity in the area of Bands 1-6 a sharp band at pI 5.1 was observed with both enzyme stains. This latter band was also present in metachromatic leukodystrophy fibroblast extracts. However, in this case the band did not appear when the specific aryl-sulfatase A stain was used. Enzyme Bands 1, 2 and 3 from urine were isolated by extraction of the gel. The three bands refocused in their initial positions; showed nearly identical enzymatic activities toward methylumbelliferyl sulfate, mitrocatechol sulfate, cerebroside sulfate and ascorbic acid 2-sulfate; and demonstrated equivalent immunological competence by antibody titration. The banding pattern of urinary arylsulfatase A was unchanged with neuraminidase treatment, whereas Bands 4-6 of the liver enzyme were converted to Bands 1-3 by this treatment. It appears that Bands 4-6 are due to sialylation of aryl-sulfatase A but that Bands 1-3 are probably due to some other type of post-ribosomal protein modification."}
{"id": "PMID:9993", "title": "Coupling of the Penicillium duponti acid protease to ethylene-maleic acid (1 : 1) linear copolymer. Preparation and properties of the water-soluble derivative.", "content": "The coupling of the thermostable acid protease (EC 3.4.23.-) of Penicillium duponti K 1014 to ethylene-maleic acid (1 : 1) linear copolymer in the presence of 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide at pH 3.0, afforded a soluble enzyme derivative with a protein incorporation yield of 67% under optimal conditions. The protein content of the enzyme-polymer complex, the molecular weights of the reactants, and the mean value of 2.2 lysine residues per mol of enzyme found in amide linkage to the matrix, support a structure consisting of two polymer chains per mol of protease, each chain acylating a single lysine residue of the enzyme. The isoelectric point of the coupled enzyme was found to be 3,47, a value lower than that measured on the free protease (3.81). The specific activity of the bound protease against casein, at pH 3.7 and 30 degrees C, was 34% of that of the free enzyme, and at 75 degrees C increased to 70%. The increased size of the coupled enzyme resulted in an improved retention of activity by ultrafiltration membranes over that observed with free protease, alone or in admixture with ethylene-maleic acid copolymer. A water-soluble, coupled pepsin was prepared in 43% yield on protein basis by using the aminoethylmonoamide of ethylene-maleic acid copolymer and the same water-soluble carbodiimide.", "contents": "Coupling of the Penicillium duponti acid protease to ethylene-maleic acid (1 : 1) linear copolymer. Preparation and properties of the water-soluble derivative. The coupling of the thermostable acid protease (EC 3.4.23.-) of Penicillium duponti K 1014 to ethylene-maleic acid (1 : 1) linear copolymer in the presence of 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide at pH 3.0, afforded a soluble enzyme derivative with a protein incorporation yield of 67% under optimal conditions. The protein content of the enzyme-polymer complex, the molecular weights of the reactants, and the mean value of 2.2 lysine residues per mol of enzyme found in amide linkage to the matrix, support a structure consisting of two polymer chains per mol of protease, each chain acylating a single lysine residue of the enzyme. The isoelectric point of the coupled enzyme was found to be 3,47, a value lower than that measured on the free protease (3.81). The specific activity of the bound protease against casein, at pH 3.7 and 30 degrees C, was 34% of that of the free enzyme, and at 75 degrees C increased to 70%. The increased size of the coupled enzyme resulted in an improved retention of activity by ultrafiltration membranes over that observed with free protease, alone or in admixture with ethylene-maleic acid copolymer. A water-soluble, coupled pepsin was prepared in 43% yield on protein basis by using the aminoethylmonoamide of ethylene-maleic acid copolymer and the same water-soluble carbodiimide."}
{"id": "PMID:9994", "title": "Neutral elastolytic proteinase from canine leucocytes. Purification and characterization.", "content": "1. A neutral proteinase (EC 3.4.-.-) with elastolytic activity was isolated from canine bloodstream leucocytes, and purified to apparent homogeneity by a two-step procedure consisting of DEAE-Sephadex chromatography and molecular sieving on Sephadex G-75. 2. The molecular weight of the enzyme was 23 500, and the absorbance (A1%1cm) at 282 nm was 6.1. Amino acid analysis showed high content of glycine, aspartic acid, and valine, and low proportion of methionine, lysine and histidine as well as the absence of tyrosine in the enzyme molecule. 3. The proteinase was active against several protein substrates as well as towards N-t-butyloxycarbonyl-L-alanine p-nitrophenyl ester, N-acetyl-L-alanyl-tyrosine ethyl ester. 4. The enzyme was inactivated by diisopropylfluorophosphate, N-acetyl-L-alanyl-L-alanyl-L-alanine chloromethyl ketone, and N-p-tosyl-L-phenylalanine chloromethyl ketone. Inhibition by some natural proteinase inhibitors was also noted.", "contents": "Neutral elastolytic proteinase from canine leucocytes. Purification and characterization. 1. A neutral proteinase (EC 3.4.-.-) with elastolytic activity was isolated from canine bloodstream leucocytes, and purified to apparent homogeneity by a two-step procedure consisting of DEAE-Sephadex chromatography and molecular sieving on Sephadex G-75. 2. The molecular weight of the enzyme was 23 500, and the absorbance (A1%1cm) at 282 nm was 6.1. Amino acid analysis showed high content of glycine, aspartic acid, and valine, and low proportion of methionine, lysine and histidine as well as the absence of tyrosine in the enzyme molecule. 3. The proteinase was active against several protein substrates as well as towards N-t-butyloxycarbonyl-L-alanine p-nitrophenyl ester, N-acetyl-L-alanyl-tyrosine ethyl ester. 4. The enzyme was inactivated by diisopropylfluorophosphate, N-acetyl-L-alanyl-L-alanyl-L-alanine chloromethyl ketone, and N-p-tosyl-L-phenylalanine chloromethyl ketone. Inhibition by some natural proteinase inhibitors was also noted."}
{"id": "PMID:9995", "title": "Purification and properties of the extracellular metallo-proteinases of Chromobacterium lividum (NCIB 10926).", "content": "Four extracellular proteolytic enzymes (I-IV) (EC 3.4.22.-) were identified in static cultures of Chromobacterium lividum (NCIB 10926) by agar gel electrophoresis and isoelectric focusing. Proteinases I-III were freed of non-enzymic protein by chromatography on TEAE-cellulose and CM-cellulose. The enzyme mixture was then fractionated in a pH gradient by isoelectric focusing. All three enzymes were shown to be heat-labile metallo-enzymes. Optimal activity occurred at pH 5.6 for enzyme I and at pH 6.2 for enzymes II and III. Remazolbrilliant Blue-hide powder was a sensitive substrate for these enzymes. Proteinase I was also shown to degrade haemoglobin and casein effectively, but not myoglobin, ovalbumin or bovine serum albumin. Proteinases I-III exhibited molecular weight values of 75 000, 72 000 and 67 000 by exclusion chromatography and 71 000 and 66 000 by sodium dodecyl sulphate-poly-acrylamide-gel electrophoresis for enzyme I and II, respectively. The amino acid compositions of enzymes I and II were somewhat similar. Proteinase I was inhibited by  EDTA, 1,2-di(2-aminoethoxy)ethane-N,N,N',N'-tetraacetic activity. Mg2+ could substitute for Ca2+ or Mn2+ for Co2+. The interrelationship of proteinases I-III is discussed.", "contents": "Purification and properties of the extracellular metallo-proteinases of Chromobacterium lividum (NCIB 10926). Four extracellular proteolytic enzymes (I-IV) (EC 3.4.22.-) were identified in static cultures of Chromobacterium lividum (NCIB 10926) by agar gel electrophoresis and isoelectric focusing. Proteinases I-III were freed of non-enzymic protein by chromatography on TEAE-cellulose and CM-cellulose. The enzyme mixture was then fractionated in a pH gradient by isoelectric focusing. All three enzymes were shown to be heat-labile metallo-enzymes. Optimal activity occurred at pH 5.6 for enzyme I and at pH 6.2 for enzymes II and III. Remazolbrilliant Blue-hide powder was a sensitive substrate for these enzymes. Proteinase I was also shown to degrade haemoglobin and casein effectively, but not myoglobin, ovalbumin or bovine serum albumin. Proteinases I-III exhibited molecular weight values of 75 000, 72 000 and 67 000 by exclusion chromatography and 71 000 and 66 000 by sodium dodecyl sulphate-poly-acrylamide-gel electrophoresis for enzyme I and II, respectively. The amino acid compositions of enzymes I and II were somewhat similar. Proteinase I was inhibited by  EDTA, 1,2-di(2-aminoethoxy)ethane-N,N,N',N'-tetraacetic activity. Mg2+ could substitute for Ca2+ or Mn2+ for Co2+. The interrelationship of proteinases I-III is discussed."}
{"id": "PMID:9996", "title": "Photocontrol of urease activity in spiropyran collagen membrane.", "content": "1. Collagen fibrils were modified with beta-1-[3,3-dimethyl-6'-nitrospiro-(indoline-2,2'-2H-benzopyran)] propionic anhydride. 2. Urease (urea amidohydrolase, EC 3.5.1.5) was immobilized in spiropyran collagen membrane. The activity of the urease-spiropyran collagen membrane was found to increase in the dark and then decrease with visible light irradiation. 3. The optimum pH of the urease-spiropyran collagen membrane under visible light was lowered in the dark. 4. The apparent Michaelis constant (K'm) of the urease-spiropyran collagen membrane in the dark was almost the same as that under visible light. The apparent maximum velocity was increased in the dark. 5. The diffusion coefficient of urea through the spiropyran collagen membrane in the dark was 1.4 times that under visible light. However, the increase of the diffusion rate was not responsible for the activity increase of the urease-spiropyran collagen membrane.", "contents": "Photocontrol of urease activity in spiropyran collagen membrane. 1. Collagen fibrils were modified with beta-1-[3,3-dimethyl-6'-nitrospiro-(indoline-2,2'-2H-benzopyran)] propionic anhydride. 2. Urease (urea amidohydrolase, EC 3.5.1.5) was immobilized in spiropyran collagen membrane. The activity of the urease-spiropyran collagen membrane was found to increase in the dark and then decrease with visible light irradiation. 3. The optimum pH of the urease-spiropyran collagen membrane under visible light was lowered in the dark. 4. The apparent Michaelis constant (K'm) of the urease-spiropyran collagen membrane in the dark was almost the same as that under visible light. The apparent maximum velocity was increased in the dark. 5. The diffusion coefficient of urea through the spiropyran collagen membrane in the dark was 1.4 times that under visible light. However, the increase of the diffusion rate was not responsible for the activity increase of the urease-spiropyran collagen membrane."}
{"id": "PMID:9997", "title": "Magnetic studies of Chromatium flavocytochrome C552. A mechanism for heme-flavin interaction.", "content": "Electron paramagnetic resonance and magnetic susceptibility studies of Chromatium flavocytochrome C552 and its diheme flavin-free subunit at temperatures below 45 degrees K are reported. The results show that in the intact protein and the subunit the two low-spin (S = 1/2) heme irons are distinguishable, giving rise to separate EPR signals. In the intact protein only, one of the heme irons exists in two different low spin environments in the pH range 5.5 to 10.5, while the other remains in a constant environment. Factors influencing the variable heme iron environment also influence flavin reactivity, indicating the existence of a mechanism for heme-flavin interaction.", "contents": "Magnetic studies of Chromatium flavocytochrome C552. A mechanism for heme-flavin interaction. Electron paramagnetic resonance and magnetic susceptibility studies of Chromatium flavocytochrome C552 and its diheme flavin-free subunit at temperatures below 45 degrees K are reported. The results show that in the intact protein and the subunit the two low-spin (S = 1/2) heme irons are distinguishable, giving rise to separate EPR signals. In the intact protein only, one of the heme irons exists in two different low spin environments in the pH range 5.5 to 10.5, while the other remains in a constant environment. Factors influencing the variable heme iron environment also influence flavin reactivity, indicating the existence of a mechanism for heme-flavin interaction."}
{"id": "PMID:9998", "title": "Conformational transitions of monellin, an intensely sweet protein.", "content": "Conformational transitions of monellin, an intensely sweet protein from the berries of Dioscoreophyllum cumminsii, were studied by the circular dichroism (CD) probe. According to the CD spectra, monellin has a low content of the helical structure and a significant amount of the pleated sheet (beta) conformation. The native conformation was found to be sensitive to alkali, sodium dodecyl sulfate, and guanidine-HC1, but it was stable in acid (e.g. pH 2.4) as shown by CD and persistence or the disappearance of sweet taste. The main chain conformation of the alkali-denatured monellin (pH 10.9) was restored upon acidification (pH 3.3) of the alkaline solutions. The tertiary structure, however, was not completely restroed, as indicated by CD in the 230-300 nm spectral zone, although the sweet taste reappeared. If the pH of a neutral solution was raised to 9.6, the CD in the near ultraviolet was significantly altered, though the sweet taste persisted. This indicates that a slight conformational change did not interfere with the effects on the taste buds. While sodium dodecyl sulfate readily disorganized the tertiary structure, the main chain was reconstructed by this reagent into a new form of higher helix content than in the native macromolecule. Reconstruction into a modified conformation of higher helix content was achieved also with 50% ethanol. The main chain conformation was not affected by 25% ethanol which produced slight changes in the CD at 230-260 nm zone and did not abolish the sweet taste.", "contents": "Conformational transitions of monellin, an intensely sweet protein. Conformational transitions of monellin, an intensely sweet protein from the berries of Dioscoreophyllum cumminsii, were studied by the circular dichroism (CD) probe. According to the CD spectra, monellin has a low content of the helical structure and a significant amount of the pleated sheet (beta) conformation. The native conformation was found to be sensitive to alkali, sodium dodecyl sulfate, and guanidine-HC1, but it was stable in acid (e.g. pH 2.4) as shown by CD and persistence or the disappearance of sweet taste. The main chain conformation of the alkali-denatured monellin (pH 10.9) was restored upon acidification (pH 3.3) of the alkaline solutions. The tertiary structure, however, was not completely restroed, as indicated by CD in the 230-300 nm spectral zone, although the sweet taste reappeared. If the pH of a neutral solution was raised to 9.6, the CD in the near ultraviolet was significantly altered, though the sweet taste persisted. This indicates that a slight conformational change did not interfere with the effects on the taste buds. While sodium dodecyl sulfate readily disorganized the tertiary structure, the main chain was reconstructed by this reagent into a new form of higher helix content than in the native macromolecule. Reconstruction into a modified conformation of higher helix content was achieved also with 50% ethanol. The main chain conformation was not affected by 25% ethanol which produced slight changes in the CD at 230-260 nm zone and did not abolish the sweet taste."}
{"id": "PMID:9999", "title": "In vitro activation of glycoprotein hormones. Hybridization of subunits from thyrotropin, lutropin and human choriogonadotropin.", "content": "In vitro assembly of thyrotropin alpha and beta subunits led to an increase in content of alpha helix and beta sheet very similar to that found for gonadotropins. This association-dependent active folding involved the burying of three tyrosine residues tentatively assigned to Tyr alpha 41, Tyr beta 37 and Tyr beta 59 and common to all studied glycoprotein hormones. In vitro hybridizations between alpha and beta subunits of various hormones (thyrotropin, lutropin and choriogonadotropin) from different species (ovine, bovine and human) triggered the same molecular events as assembly of homologous subunits: the burying of three tyrosine residues and the increase of periodic structure of the folding. These changes are slow, time-dependent processes. Rates and yields of hybrid formation measured by sedimentation analysis and difference spectroscopy of tyrosines are identical, within experimental error, with the rates and yields measured by the recovery of the biological activity either the stimulation of chick thyroids for thyrotropin-beta hybrids or binding to porcine testis receptors for gonadotropin-beta hybrids. Whatever the origin of the alpha subunit, the thyrotropin-beta hybrids were not able to bind to testis receptors although active on chick thyroids. Rates and yields of hybrid formation essentially depended on the origin of the beta subunit. All the hybrids could be dissociated at acid pH with rates similar to those of native hormone. The extension to thyrotropin and various hybrids of the structural features of the in vitro assembly already recognized for gonadotropins strengthens the hypothesis that one deals with a basic activation process which also occurs in vivo after the synthesis of the subunits.", "contents": "In vitro activation of glycoprotein hormones. Hybridization of subunits from thyrotropin, lutropin and human choriogonadotropin. In vitro assembly of thyrotropin alpha and beta subunits led to an increase in content of alpha helix and beta sheet very similar to that found for gonadotropins. This association-dependent active folding involved the burying of three tyrosine residues tentatively assigned to Tyr alpha 41, Tyr beta 37 and Tyr beta 59 and common to all studied glycoprotein hormones. In vitro hybridizations between alpha and beta subunits of various hormones (thyrotropin, lutropin and choriogonadotropin) from different species (ovine, bovine and human) triggered the same molecular events as assembly of homologous subunits: the burying of three tyrosine residues and the increase of periodic structure of the folding. These changes are slow, time-dependent processes. Rates and yields of hybrid formation measured by sedimentation analysis and difference spectroscopy of tyrosines are identical, within experimental error, with the rates and yields measured by the recovery of the biological activity either the stimulation of chick thyroids for thyrotropin-beta hybrids or binding to porcine testis receptors for gonadotropin-beta hybrids. Whatever the origin of the alpha subunit, the thyrotropin-beta hybrids were not able to bind to testis receptors although active on chick thyroids. Rates and yields of hybrid formation essentially depended on the origin of the beta subunit. All the hybrids could be dissociated at acid pH with rates similar to those of native hormone. The extension to thyrotropin and various hybrids of the structural features of the in vitro assembly already recognized for gonadotropins strengthens the hypothesis that one deals with a basic activation process which also occurs in vivo after the synthesis of the subunits."}
{"id": "PMID:10000", "title": "A new method for the determination of alpha1-protease inhibitor (alpha1-antitrypsin) phenotypes based on the formation of alpha1-protease inhibitor allele product-elastase complexes.", "content": "Up until now it has been assumed that the protease-binding property of alpha1-protease inhibitor (alpha1PI) was destroyed by acid starch gel electrophoresis (pH 4.9). Analyses on acid starch gel blocks for pH and conductivity changes during and following a typical electrophoretic run showed that it was unlikely that the separating alpha1PI would be exposed to pH values lower than 6.2, and that the allele products, following the passage of the buffer front, were in an environment of constant pH(6.3), extremely low conductivity and high field strength. These results strongly suggested the likelihood that alpha1-PI would be chemically and physically unchanged as a result of exposure to acid starch gel electrophoresis. In order to test this likelihood, human serum was electrophoretically separated in acid starch gel and following electrophoresis, was immersed in 0.1 M diethylbarbiturate buffer, pH 8.6, containing 20 mug/ml of pancreatic elastase. The pH-adjusted (8.15) and elastase-impregnated starch gel layer was superimposed on hemoglobin-agar for 2.5 h at 37 degrees C followed by immersion of the hemoglobin-agar layer in 1% NaCl overnight, distilled water for 2 h, drying under filter paper and staining. The results showed zones of undigested hemoglobin indicating, unequivocally, that the separated alpha1PI allele products are capable of forming complexes with proteases and that alpha1PI is not inactivated following exposure to acid starch gel electrophoresis. Densitometric analysis of the transparent stained zones on a clear agar gel background offers an alternative to analysis of the acid starch gel-separated zones by antigen-antibody crossed electrophoresis and as such is suitable for identification of alpha1-protease inhibitor phenotypes. Further, the method is specific for alpha1PI and a densitometric scan provides direct information relative to the protease-binding capacity of the sample as well as the contribution of each alpha1PI allele product to that capacity.", "contents": "A new method for the determination of alpha1-protease inhibitor (alpha1-antitrypsin) phenotypes based on the formation of alpha1-protease inhibitor allele product-elastase complexes. Up until now it has been assumed that the protease-binding property of alpha1-protease inhibitor (alpha1PI) was destroyed by acid starch gel electrophoresis (pH 4.9). Analyses on acid starch gel blocks for pH and conductivity changes during and following a typical electrophoretic run showed that it was unlikely that the separating alpha1PI would be exposed to pH values lower than 6.2, and that the allele products, following the passage of the buffer front, were in an environment of constant pH(6.3), extremely low conductivity and high field strength. These results strongly suggested the likelihood that alpha1-PI would be chemically and physically unchanged as a result of exposure to acid starch gel electrophoresis. In order to test this likelihood, human serum was electrophoretically separated in acid starch gel and following electrophoresis, was immersed in 0.1 M diethylbarbiturate buffer, pH 8.6, containing 20 mug/ml of pancreatic elastase. The pH-adjusted (8.15) and elastase-impregnated starch gel layer was superimposed on hemoglobin-agar for 2.5 h at 37 degrees C followed by immersion of the hemoglobin-agar layer in 1% NaCl overnight, distilled water for 2 h, drying under filter paper and staining. The results showed zones of undigested hemoglobin indicating, unequivocally, that the separated alpha1PI allele products are capable of forming complexes with proteases and that alpha1PI is not inactivated following exposure to acid starch gel electrophoresis. Densitometric analysis of the transparent stained zones on a clear agar gel background offers an alternative to analysis of the acid starch gel-separated zones by antigen-antibody crossed electrophoresis and as such is suitable for identification of alpha1-protease inhibitor phenotypes. Further, the method is specific for alpha1PI and a densitometric scan provides direct information relative to the protease-binding capacity of the sample as well as the contribution of each alpha1PI allele product to that capacity."}
{"id": "PMID:10001", "title": "Study of the biological significance of cytochrome methylation. I. Thermal, acid and guanidinium hydrochloride denaturations of baker's yeast ferricytochromes c.", "content": "The iso-cytochromes c from baker's yeast: iso-1 methylated and unmethylated forms and iso-2 have been purified and their stabilities towards denaturants compared to that of horse heart cytochrome c. Thermal, acid and guanidinium hydrochloride denaturations were followed using fluorescence emission of their tryptophan 59 and/or the absorbance in the Soret region as the physical parameters. Very few differences could be evidenced among the ferricytochromes investigated in this study insofar as the acid denaturations are concerned. This is to be contrasted with the conclusions of the thermal and guanidinium hydrochloride denaturations studies which clearly showed the ferricytochrome from horse heart to be much more stable than those from baker's yeast. No appreciable differences could be measured among the methylated and unmethylated forms of iso-1 cytochrome c nor among iso-1 and iso-2 cytochromes from baker's yeast. Our results suggest that a stabilizing effect of methylation on the tridimensional structure of ferricytochrome c must probably be discarded. Other possible physiological roles of methylation are suggested taking into account the relative instability of ascomycetes's cytochromes as compared to mammalian ones.", "contents": "Study of the biological significance of cytochrome methylation. I. Thermal, acid and guanidinium hydrochloride denaturations of baker's yeast ferricytochromes c. The iso-cytochromes c from baker's yeast: iso-1 methylated and unmethylated forms and iso-2 have been purified and their stabilities towards denaturants compared to that of horse heart cytochrome c. Thermal, acid and guanidinium hydrochloride denaturations were followed using fluorescence emission of their tryptophan 59 and/or the absorbance in the Soret region as the physical parameters. Very few differences could be evidenced among the ferricytochromes investigated in this study insofar as the acid denaturations are concerned. This is to be contrasted with the conclusions of the thermal and guanidinium hydrochloride denaturations studies which clearly showed the ferricytochrome from horse heart to be much more stable than those from baker's yeast. No appreciable differences could be measured among the methylated and unmethylated forms of iso-1 cytochrome c nor among iso-1 and iso-2 cytochromes from baker's yeast. Our results suggest that a stabilizing effect of methylation on the tridimensional structure of ferricytochrome c must probably be discarded. Other possible physiological roles of methylation are suggested taking into account the relative instability of ascomycetes's cytochromes as compared to mammalian ones."}
{"id": "PMID:10002", "title": "Physical studies on the size and structure of the covalently closed circular chloroplast DNA from higher plants.", "content": "The size and structure of the covalently closed circular chloroplast DNAs (ctDNA) from pea, lettuce, and spinach plants, have been studied by analytical ultracentrifugation. The values of so20,w,Na+ of the native and denatured forms of the open and closed circular DNAs from these plants have been determined. The absolute molecular weight of purified closed circular pea ctDNA monomers has been determined by buoyant equilibrium sedimentation to be 89.1 (S.D. +/- 0.7)-10(6). The value of the so20,w,Na+ of open circular pea ctDNA and its molecular weight, in conjunction with corresponding values for other sizes of circular DNA, has been used to derive an empirical relationship between so20,w,Na+ and molecular weight for open circular DNAs. Using this relationship, the molecular weights of lettuce and spinach ctDNAs have been determined to be 98.2 (S.D. +/- 1.5)-10(6) and 97.2 (S.D. +/- 1.5)-10(6), respectively. At pH values 12.7 and 13, closed circular lettuce and pea ctDNAs have been found to exist as mixtures of reversibly and irreversibly denatured closed circular DNAs.", "contents": "Physical studies on the size and structure of the covalently closed circular chloroplast DNA from higher plants. The size and structure of the covalently closed circular chloroplast DNAs (ctDNA) from pea, lettuce, and spinach plants, have been studied by analytical ultracentrifugation. The values of so20,w,Na+ of the native and denatured forms of the open and closed circular DNAs from these plants have been determined. The absolute molecular weight of purified closed circular pea ctDNA monomers has been determined by buoyant equilibrium sedimentation to be 89.1 (S.D. +/- 0.7)-10(6). The value of the so20,w,Na+ of open circular pea ctDNA and its molecular weight, in conjunction with corresponding values for other sizes of circular DNA, has been used to derive an empirical relationship between so20,w,Na+ and molecular weight for open circular DNAs. Using this relationship, the molecular weights of lettuce and spinach ctDNAs have been determined to be 98.2 (S.D. +/- 1.5)-10(6) and 97.2 (S.D. +/- 1.5)-10(6), respectively. At pH values 12.7 and 13, closed circular lettuce and pea ctDNAs have been found to exist as mixtures of reversibly and irreversibly denatured closed circular DNAs."}
{"id": "PMID:10003", "title": "Further characterization of a DNA polymerase activity in mouse sperm nuclei.", "content": "The presence of a nuclear DNA polymerase in mouse sperm from adult testes has been confirmed and the properties of this enzyme further investigated. This activity was shown to be greatly enhanced by treating the spermatozoa with methanol or ethanol before incubation in the reaction medium or by their addition in small amounts to this medium. It was protected against degradation by nuclear proteases by adding soybean trypsin inhibitor and was stimulated by ATP. It was found to be Mg2+ dependent (optimum concentration: 7.5 mM), DNA dependent, and all four deoxynucleoside triphosphates were needed for optimal reaction. The radioactive acid-precipitable product of polymerization was not eliminated by organic solvents, nor by pronase, ribonuclease or by nuclease S1; however, it was converted to a large extent to acid-soluble products by pancreatic deoxyribonuclease. Since it was only partially solubilized by Triton X-100, it therefore did not appear to be preferentially associated with the nuclear membranes. The activity recovered after incubation depended also on the pH (optimum at pH 8.3) and did not work well in a medium for DNA polymerase alpha. The temperature for maximum incorporation of nucleotides was found to be 32 degrees C and, under our conditions, the reaction was linear for 30 min. The DNA polymerase activity was inhibited by low and high concentrations of KCl. It was not lowered by N-ethylmaleimide or p-hydroxymercuribenzoate; urea slightly stimulated the reaction and this stimulation was reversed by subsequent treatment with N-ethylmaleimide. Actinomycin D (40 mug/ml), ethidium bromide (25--50 muM), netropsin (5--50 mug/ml), and spermidine (0.5--2.5 mM) lowered the polymerization of DNA precursors. The nuclear enzyme could shift from the endogenous template to activated exogenous calf thymus DNA, the resulting nuclear radioactivity being reduced. The endogenous DNP template ability was not increased by deoxyribonuclease activation according to the method of Aposhian and Kornberg (J. Biol. Chem. (1962) 237, 519--525) suggesting that the amount of DNA polymerase associated with chromatin was probably limiting the reaction. The DNA polymerase activity detected in mouse sperm nuclei has numerous properties of low molecular weight DNA polymerases (DNA polymerase beta) reported in several eukaryotic organisms.", "contents": "Further characterization of a DNA polymerase activity in mouse sperm nuclei. The presence of a nuclear DNA polymerase in mouse sperm from adult testes has been confirmed and the properties of this enzyme further investigated. This activity was shown to be greatly enhanced by treating the spermatozoa with methanol or ethanol before incubation in the reaction medium or by their addition in small amounts to this medium. It was protected against degradation by nuclear proteases by adding soybean trypsin inhibitor and was stimulated by ATP. It was found to be Mg2+ dependent (optimum concentration: 7.5 mM), DNA dependent, and all four deoxynucleoside triphosphates were needed for optimal reaction. The radioactive acid-precipitable product of polymerization was not eliminated by organic solvents, nor by pronase, ribonuclease or by nuclease S1; however, it was converted to a large extent to acid-soluble products by pancreatic deoxyribonuclease. Since it was only partially solubilized by Triton X-100, it therefore did not appear to be preferentially associated with the nuclear membranes. The activity recovered after incubation depended also on the pH (optimum at pH 8.3) and did not work well in a medium for DNA polymerase alpha. The temperature for maximum incorporation of nucleotides was found to be 32 degrees C and, under our conditions, the reaction was linear for 30 min. The DNA polymerase activity was inhibited by low and high concentrations of KCl. It was not lowered by N-ethylmaleimide or p-hydroxymercuribenzoate; urea slightly stimulated the reaction and this stimulation was reversed by subsequent treatment with N-ethylmaleimide. Actinomycin D (40 mug/ml), ethidium bromide (25--50 muM), netropsin (5--50 mug/ml), and spermidine (0.5--2.5 mM) lowered the polymerization of DNA precursors. The nuclear enzyme could shift from the endogenous template to activated exogenous calf thymus DNA, the resulting nuclear radioactivity being reduced. The endogenous DNP template ability was not increased by deoxyribonuclease activation according to the method of Aposhian and Kornberg (J. Biol. Chem. (1962) 237, 519--525) suggesting that the amount of DNA polymerase associated with chromatin was probably limiting the reaction. The DNA polymerase activity detected in mouse sperm nuclei has numerous properties of low molecular weight DNA polymerases (DNA polymerase beta) reported in several eukaryotic organisms."}
{"id": "PMID:10004", "title": "The rye embryo system as an alternative to the wheat system for protein synthesis in vitro.", "content": "Isolated rye embryos are a readily available source for the preparation of very active, cell-free, protein-synthesizing systems. Incorporation levels up to 2000 pmol leucine per 50 mul assay are routinely obtained at saturating TMV (Tobacco mosaic virus) RNA concentrations; at limiting messenger RNA concentrations the incorporation exceeds 1000 leucine molecules per TMV RNA molecule. The characteristics of this cell-free system for the translation of TMV RNA are identical with those of a similarly prepared wheat germ system. The major advantage of the rye embryo system is its high reliability as compared to the unpredictable wheat germ system. Sucrose gradient analysis of the reaction mixture during the incubation shows an extensive polysome formation with TMV RNA and demonstrates efficient polypeptide chain release.", "contents": "The rye embryo system as an alternative to the wheat system for protein synthesis in vitro. Isolated rye embryos are a readily available source for the preparation of very active, cell-free, protein-synthesizing systems. Incorporation levels up to 2000 pmol leucine per 50 mul assay are routinely obtained at saturating TMV (Tobacco mosaic virus) RNA concentrations; at limiting messenger RNA concentrations the incorporation exceeds 1000 leucine molecules per TMV RNA molecule. The characteristics of this cell-free system for the translation of TMV RNA are identical with those of a similarly prepared wheat germ system. The major advantage of the rye embryo system is its high reliability as compared to the unpredictable wheat germ system. Sucrose gradient analysis of the reaction mixture during the incubation shows an extensive polysome formation with TMV RNA and demonstrates efficient polypeptide chain release."}
{"id": "PMID:10005", "title": "Raman pH profiles for nucleic acid constituents I. Cytidine and uridine ribonucleosides.", "content": "Raman spectra of aqueous solutions of uridine and cytidine have been recorded as a function of pH with the band intensities and vibrational frequencies monitored to determine bands which may be considered as diagnostic of the concentration of the various species. Quantitative band intensity measurements indicate that not all pH-sensitive bands can be considered as diagnostic of the pK value for the acid form of the nucleoside, and for the percent species in solution. Although the accuracy of the Raman band intensity method is inherently less than that of the titrimetric or visible-ultraviolet spectrophotometric methods, the pK values and percent species agree well with those obtained from these methods. The utility of the results obtained from the pH profiles for cytidine is discussed in terms of the effect of acidification on the structural and conformational characteristics of polycytidylic acid in solution.", "contents": "Raman pH profiles for nucleic acid constituents I. Cytidine and uridine ribonucleosides. Raman spectra of aqueous solutions of uridine and cytidine have been recorded as a function of pH with the band intensities and vibrational frequencies monitored to determine bands which may be considered as diagnostic of the concentration of the various species. Quantitative band intensity measurements indicate that not all pH-sensitive bands can be considered as diagnostic of the pK value for the acid form of the nucleoside, and for the percent species in solution. Although the accuracy of the Raman band intensity method is inherently less than that of the titrimetric or visible-ultraviolet spectrophotometric methods, the pK values and percent species agree well with those obtained from these methods. The utility of the results obtained from the pH profiles for cytidine is discussed in terms of the effect of acidification on the structural and conformational characteristics of polycytidylic acid in solution."}
{"id": "PMID:10006", "title": "Raman ph profiles for nucleic acid constituents. II. 5'-AMP and 5'-GMP ribonucleotides.", "content": "Raman spectra of aqueous solutions of 5'-AMP and 5'-GMP have been recorded as a function of pH. Band intensities and frequencies have been monitored to determine bands which may be considered as diagnostic for the concentration and the pK of the solution species. Quantitative band intensity measurements indicate only a selected number of bands can be considered as diagnostic of the base or the secondary phosphate proton dissociation. The utility of the pH profiles derived from specific band intensity variations for 5'-AMP is discussed in terms of the effect of acidification on solution characteristics of polyadenylic acid.", "contents": "Raman ph profiles for nucleic acid constituents. II. 5'-AMP and 5'-GMP ribonucleotides. Raman spectra of aqueous solutions of 5'-AMP and 5'-GMP have been recorded as a function of pH. Band intensities and frequencies have been monitored to determine bands which may be considered as diagnostic for the concentration and the pK of the solution species. Quantitative band intensity measurements indicate only a selected number of bands can be considered as diagnostic of the base or the secondary phosphate proton dissociation. The utility of the pH profiles derived from specific band intensity variations for 5'-AMP is discussed in terms of the effect of acidification on solution characteristics of polyadenylic acid."}
{"id": "PMID:10007", "title": "Solubility of phospholipid polar group model compounds in water.", "content": "The aqueous solubilities of the Na+ and Ca2+ salts and the free acid forms of phosphorylcholine, phosphorylethanolamine and D,L-phospho-serine, respectively, were found to be below the polar group concentrations calculated for bilayers of the corresponding phospholipids.", "contents": "Solubility of phospholipid polar group model compounds in water. The aqueous solubilities of the Na+ and Ca2+ salts and the free acid forms of phosphorylcholine, phosphorylethanolamine and D,L-phospho-serine, respectively, were found to be below the polar group concentrations calculated for bilayers of the corresponding phospholipids."}
{"id": "PMID:10008", "title": "Photophosphorylation as a function of illumination time. II. Effects of permeant buffers.", "content": "(1) The amounts of orthophosphate, bicarbonate and tris (hydroxymethyl)-aminomethane found inside the thylakoid are almost exactly the amounts predicted by assuming that the buffers equilibrate across the membrane. Since imidazole and pyridine delay the development of post-illumination ATP formation while increasing the maximum amount of ATP formed, it follows that such relatively permeant buffers must also enter the inner aqueous space of the thylakoid. (2) Photophosphorylation begins abruptly at full steady-state efficiency and full steady-state rate as soon as the illumination time exceeds about 5 ms when permeant ions are absent or as soon as the time exceeds about 50 ms if valinomycin and KC1 are present. In either case, permeant buffers have little or no effect on the time of illumination required to initiate phosphorylation. A concentration of bicarbonate which would delay acidification of the bulk of the inner aqueous phase for at least 350 ms has no effect at all on the time of initiation of phosphorylation. In somewhat swollen chloroplasts, the combined buffering by the tris(hydroxymethyl) aminomethane and orthophosphate inside would delay acidification of the inside by 1500 ms but, even in the presence of valinomycin and KC1, the total delay in the initiation of phosphorylation is then only 65 ms. Similar discrepancies occur with all of the other buffers mentioned. (3) Since these discrepancies between internal acidification and phosphorylation are found in the presence of saturating amounts of valinomycin and KC1, it seems that photophosphorylation can occur when there are no proton concentration gradients and no electrical potential differences across the membranes which separate the medium from the greater part of the internal aqueous phase. (4) We suggest that the protons produced by electron transport may be used directly for phosphorylation without even entering the bulk of the inner aqueous phase of the lamellar system. If so, phosphorylation could proceed long before the internal pH reflected the proton activity gradients within the membrane.", "contents": "Photophosphorylation as a function of illumination time. II. Effects of permeant buffers. (1) The amounts of orthophosphate, bicarbonate and tris (hydroxymethyl)-aminomethane found inside the thylakoid are almost exactly the amounts predicted by assuming that the buffers equilibrate across the membrane. Since imidazole and pyridine delay the development of post-illumination ATP formation while increasing the maximum amount of ATP formed, it follows that such relatively permeant buffers must also enter the inner aqueous space of the thylakoid. (2) Photophosphorylation begins abruptly at full steady-state efficiency and full steady-state rate as soon as the illumination time exceeds about 5 ms when permeant ions are absent or as soon as the time exceeds about 50 ms if valinomycin and KC1 are present. In either case, permeant buffers have little or no effect on the time of illumination required to initiate phosphorylation. A concentration of bicarbonate which would delay acidification of the bulk of the inner aqueous phase for at least 350 ms has no effect at all on the time of initiation of phosphorylation. In somewhat swollen chloroplasts, the combined buffering by the tris(hydroxymethyl) aminomethane and orthophosphate inside would delay acidification of the inside by 1500 ms but, even in the presence of valinomycin and KC1, the total delay in the initiation of phosphorylation is then only 65 ms. Similar discrepancies occur with all of the other buffers mentioned. (3) Since these discrepancies between internal acidification and phosphorylation are found in the presence of saturating amounts of valinomycin and KC1, it seems that photophosphorylation can occur when there are no proton concentration gradients and no electrical potential differences across the membranes which separate the medium from the greater part of the internal aqueous phase. (4) We suggest that the protons produced by electron transport may be used directly for phosphorylation without even entering the bulk of the inner aqueous phase of the lamellar system. If so, phosphorylation could proceed long before the internal pH reflected the proton activity gradients within the membrane."}
{"id": "PMID:10009", "title": "Effect of ionophores A23187 and nigericin on the light-induced redistribution of Mg2+, K+ and H+ across the thylakoid membrane.", "content": "Passive redistributions of Mg2+ and K+ ions across the thylakoid membranes, occurring in association with the light-driven electrogenic influx of hydrogen ions have been examined in suspensions of broken spinach chloroplasts under a variety of conditions. (i) In accord with results of Hind el al. (Proc. Natl. Acad. Sci. U.S. (1974) 71, 1484), it was found that at a low K/Mg concentration ratio in the medium, the K-efflux is negligibly small, whereas a substantial Mg-efflux is observed. The converse is true when the K/Mg concentration ratio in the medium is high. (ii) In the presence of A23187, which was found to cause approximately a 60% inhibition of the light-induced pH-gradient, a significant influx of Mg2+ was observed in the light at a high K/Mg concentration ratio. Conversely the Mg-influx was small in the presence of A23187 when the K/Mg concentration ratio in the medium was low. Under these conditions, the Mg-influx was considerably increased upon the addition of valinomycin. A23187 was found not to affect the K-efflux in the light. (iii) The light-induced K-influx observed in the presence of nigericin also was found to be dependent on the concentration ratio of the monovalent and divalent cation. Its magnitude increased upon an increase in the K/Mg ratio. The results are interpreted in terms of a simplified model in which the total passive efflux of cations, driven by the potential set by the electrogenic proton pump, is considered to be a constant fraction of the proton influx. According to this, an increase in the flux of an ion species, induced either by raising its concentration, or by increasing its permeability through the membrane, will cause a decrease in the flux of the other cations. The relevance of the results is discussed with respect to conclusions about the involvement and relative magnitudes of the passive K and Mg effluxes across the thylakoid membrane during energization of intact chloroplasts and chloroplasts in situ.", "contents": "Effect of ionophores A23187 and nigericin on the light-induced redistribution of Mg2+, K+ and H+ across the thylakoid membrane. Passive redistributions of Mg2+ and K+ ions across the thylakoid membranes, occurring in association with the light-driven electrogenic influx of hydrogen ions have been examined in suspensions of broken spinach chloroplasts under a variety of conditions. (i) In accord with results of Hind el al. (Proc. Natl. Acad. Sci. U.S. (1974) 71, 1484), it was found that at a low K/Mg concentration ratio in the medium, the K-efflux is negligibly small, whereas a substantial Mg-efflux is observed. The converse is true when the K/Mg concentration ratio in the medium is high. (ii) In the presence of A23187, which was found to cause approximately a 60% inhibition of the light-induced pH-gradient, a significant influx of Mg2+ was observed in the light at a high K/Mg concentration ratio. Conversely the Mg-influx was small in the presence of A23187 when the K/Mg concentration ratio in the medium was low. Under these conditions, the Mg-influx was considerably increased upon the addition of valinomycin. A23187 was found not to affect the K-efflux in the light. (iii) The light-induced K-influx observed in the presence of nigericin also was found to be dependent on the concentration ratio of the monovalent and divalent cation. Its magnitude increased upon an increase in the K/Mg ratio. The results are interpreted in terms of a simplified model in which the total passive efflux of cations, driven by the potential set by the electrogenic proton pump, is considered to be a constant fraction of the proton influx. According to this, an increase in the flux of an ion species, induced either by raising its concentration, or by increasing its permeability through the membrane, will cause a decrease in the flux of the other cations. The relevance of the results is discussed with respect to conclusions about the involvement and relative magnitudes of the passive K and Mg effluxes across the thylakoid membrane during energization of intact chloroplasts and chloroplasts in situ."}
{"id": "PMID:10010", "title": "Electron paramagnetic resonance spectra of mitochondrial and microsomal cytochrome P-450 from the rat adrenal.", "content": "The electron paramagnetic resonance (EPR) spectra of rat adrenal zona fasciculate mitochondria showed peaks corresponding to low spin ferric cytochrome P-450 with apparent g values of 2.424, 2.248 and 1.917, and weak signals due to high spin ferric cytochrome P-450 with gx values of 8.08 and 7.80. The former is attributed to cholesterol side chain cleavage cytochrome P-450, the latter to 11beta-hydroxylase cytochrome P-450. On addition of deoxycorticosterone the g = 7.80 signal was elevated and there was an associated drop in the low spinal signal. As the pH was reduced from 7.4 to 6.1, the g = 8.08 signal increased with again a drop in intensity of the low spin signal. Mitochondria from the zona glomerulosa showed similar spectral properties to those described above. Addition of succinate, isocitrate or pregnenolone caused a loss of the g = 8.08 signal. Addition of calcium increased the magnitude of the g = 8.08 signal, and caused a slight reduction in the magnitude of the low spin signal. Also, addition of deoxycorticosterone, pregnenolone, succinate or isocitrate caused slight shifts of the outer lines of the low spin spectrum. Interaction of mitochondrial cytochrome P-450 with metyrapone and aminoglutethimide modified the low spinal parameters. Adrenal microsomal cytochrome P-450 had low spin ferric g values of 2.417, 2.244 and 1.919 and a high spin ferric gxy values of 7.90 and 3.85, distinct from the values obtained with mitochondria.", "contents": "Electron paramagnetic resonance spectra of mitochondrial and microsomal cytochrome P-450 from the rat adrenal. The electron paramagnetic resonance (EPR) spectra of rat adrenal zona fasciculate mitochondria showed peaks corresponding to low spin ferric cytochrome P-450 with apparent g values of 2.424, 2.248 and 1.917, and weak signals due to high spin ferric cytochrome P-450 with gx values of 8.08 and 7.80. The former is attributed to cholesterol side chain cleavage cytochrome P-450, the latter to 11beta-hydroxylase cytochrome P-450. On addition of deoxycorticosterone the g = 7.80 signal was elevated and there was an associated drop in the low spinal signal. As the pH was reduced from 7.4 to 6.1, the g = 8.08 signal increased with again a drop in intensity of the low spin signal. Mitochondria from the zona glomerulosa showed similar spectral properties to those described above. Addition of succinate, isocitrate or pregnenolone caused a loss of the g = 8.08 signal. Addition of calcium increased the magnitude of the g = 8.08 signal, and caused a slight reduction in the magnitude of the low spin signal. Also, addition of deoxycorticosterone, pregnenolone, succinate or isocitrate caused slight shifts of the outer lines of the low spin spectrum. Interaction of mitochondrial cytochrome P-450 with metyrapone and aminoglutethimide modified the low spinal parameters. Adrenal microsomal cytochrome P-450 had low spin ferric g values of 2.417, 2.244 and 1.919 and a high spin ferric gxy values of 7.90 and 3.85, distinct from the values obtained with mitochondria."}
{"id": "PMID:10011", "title": "Secretion of lecithin: cholesterol acyltransferase from isolated rat hepatocytes.", "content": "1. Lecithin:cholesterol acyltransferase is secreted from isolated rat heptocytes. 2. The secretion is stimulated when serum is added to the incubation medium. 3. Optimal conditions for secretion are: 5-10(6) hepatocytes per ml, 5 h incubation, pH 7.3-7.4 and 25% serum in the incubation medium. 4. Concomitantly with the secretion of lecithin:cholesterol acyltransferase there is a secretion of unesterified cholesterol and triacylglycerol. 5. Colchicine or cycloheximide in the incubation medium inhibits secretion of lecithin:cholesterol acyltransferase.", "contents": "Secretion of lecithin: cholesterol acyltransferase from isolated rat hepatocytes. 1. Lecithin:cholesterol acyltransferase is secreted from isolated rat heptocytes. 2. The secretion is stimulated when serum is added to the incubation medium. 3. Optimal conditions for secretion are: 5-10(6) hepatocytes per ml, 5 h incubation, pH 7.3-7.4 and 25% serum in the incubation medium. 4. Concomitantly with the secretion of lecithin:cholesterol acyltransferase there is a secretion of unesterified cholesterol and triacylglycerol. 5. Colchicine or cycloheximide in the incubation medium inhibits secretion of lecithin:cholesterol acyltransferase."}
{"id": "PMID:10012", "title": "Distinct testicular 17-ketosteroid reductases, one in interstitial tissue and one in seminiferous tubules. Differential modulation by testosterone and metabolites of testosterone.", "content": "The final step in the biosynthesis of testosterone is the reduction of androstenedione, which is catalyzed by the microsomal enzyme 17-ketosteroid reductase. Evidence is presented which suggests that there are two distinct 17-ketosteroid reductases in rat testes, one in interstitial tissue and one in seminiferous tubules. The two enzymes have different pH optima, 5.6 for the one from interstitial tissue and 6.5 for the one from seminiferous tubules. At the optimum pH, a 70-fold difference in Km values was observed, 17 muM for the interstitial tissue enzyme and 0.25 muM for the enzyme from seminiferous tubules. Testosterone and metabolites of testosterone have very different effects of each of these enzyme activities. The interstitial tissue enzyme activity is inhibited by testosterone and several 5alpha-reduced metabolites of testosterone and by estrogens. The most potent inhibitor of the steroids investigated was 5alpha-androstane-3alpha, 17beta-diol, followed by 17beta-estradiol approximately equal to dihydrotestosterone greater than testosterone greater than estrone greater than estriol. 5alpha-Androstane-3alpha, 17beta-diol and 17beta-estradiol were shown to act by competitive inhibition with apparent Ki values of 2.2 and 3.7 muM, respectively. In contrast, it was demonstrated that among the above steroids, only dihydrotestosterone inhibits the 17-ketosteroid reductase activity of seminiferous tubules and this inhibition was only observed at very high concentrations of inhibitor. Testosterone stimulated the 17-ketosteroid reductase activity of seminiferous tubules. 5alpha-Androstane-3alpha, 17beta-diol at low concentrations stimulated the enzyme activity from seminiferous tubules, while it had no effect at high concentrations. The remainder of the steroids tested had no effect on the 17-ketosteroid reductase activity of seminiferous tubules. The difference in response of the two enzyme activities suggests a mechanism for local regulation of testosterone synthesis in each testicular compartment that does not involve directly pituitary gonadotropins.", "contents": "Distinct testicular 17-ketosteroid reductases, one in interstitial tissue and one in seminiferous tubules. Differential modulation by testosterone and metabolites of testosterone. The final step in the biosynthesis of testosterone is the reduction of androstenedione, which is catalyzed by the microsomal enzyme 17-ketosteroid reductase. Evidence is presented which suggests that there are two distinct 17-ketosteroid reductases in rat testes, one in interstitial tissue and one in seminiferous tubules. The two enzymes have different pH optima, 5.6 for the one from interstitial tissue and 6.5 for the one from seminiferous tubules. At the optimum pH, a 70-fold difference in Km values was observed, 17 muM for the interstitial tissue enzyme and 0.25 muM for the enzyme from seminiferous tubules. Testosterone and metabolites of testosterone have very different effects of each of these enzyme activities. The interstitial tissue enzyme activity is inhibited by testosterone and several 5alpha-reduced metabolites of testosterone and by estrogens. The most potent inhibitor of the steroids investigated was 5alpha-androstane-3alpha, 17beta-diol, followed by 17beta-estradiol approximately equal to dihydrotestosterone greater than testosterone greater than estrone greater than estriol. 5alpha-Androstane-3alpha, 17beta-diol and 17beta-estradiol were shown to act by competitive inhibition with apparent Ki values of 2.2 and 3.7 muM, respectively. In contrast, it was demonstrated that among the above steroids, only dihydrotestosterone inhibits the 17-ketosteroid reductase activity of seminiferous tubules and this inhibition was only observed at very high concentrations of inhibitor. Testosterone stimulated the 17-ketosteroid reductase activity of seminiferous tubules. 5alpha-Androstane-3alpha, 17beta-diol at low concentrations stimulated the enzyme activity from seminiferous tubules, while it had no effect at high concentrations. The remainder of the steroids tested had no effect on the 17-ketosteroid reductase activity of seminiferous tubules. The difference in response of the two enzyme activities suggests a mechanism for local regulation of testosterone synthesis in each testicular compartment that does not involve directly pituitary gonadotropins."}
{"id": "PMID:10013", "title": "[Cathepsin D from horse spleen. II. Study of certain enzymatic properties].", "content": "This work reports some enzymatic properties of highly purified horse spleen cathepsin D. Hydrolysis rate of several proteins are compared. The Kinetic constants (Km = 4.95 10(-5) M and Vm = 1,76 delta DO/mn/mug) have been determined in the presence of a denatured haemoglobin substrate. Stability of the enzymatic preparation is discussed according to the pH, concentration and time of storage. Some investigations concerning the active site are described. Enzymatic and chemical results show that dicarboxylic and tryptophanyl residues seem to be involved in the hydrolytic process. Catalysis does not depend on sulfhydryl or seryl residues. Different salts, particularly nitrate, nitrite and polyphosphate are potent inhibitors of enzymatic activity.", "contents": "[Cathepsin D from horse spleen. II. Study of certain enzymatic properties]. This work reports some enzymatic properties of highly purified horse spleen cathepsin D. Hydrolysis rate of several proteins are compared. The Kinetic constants (Km = 4.95 10(-5) M and Vm = 1,76 delta DO/mn/mug) have been determined in the presence of a denatured haemoglobin substrate. Stability of the enzymatic preparation is discussed according to the pH, concentration and time of storage. Some investigations concerning the active site are described. Enzymatic and chemical results show that dicarboxylic and tryptophanyl residues seem to be involved in the hydrolytic process. Catalysis does not depend on sulfhydryl or seryl residues. Different salts, particularly nitrate, nitrite and polyphosphate are potent inhibitors of enzymatic activity."}
{"id": "PMID:10014", "title": "The chemical ecology of Biomphalaria glabrata: the effects of ammonia on the growth rate of juvenile snails.", "content": "When juvenile specimens of Biomphalaria glabrata were subjected to concentrations of ammonia ranging from 1-100 mug/ml in various media the following effects were observed: the addition of ammonia to borate buffered media caused mortality. Both borate and tris-buffered media caused a decrease in the growth rate of snails when compared with controls in SSW. The growth rates of the snails could be enhanced by increasing the concentration of ammonia to critical thresholds, but further increases beyond these thresholds resulted in growth inhibition. The toxicity of ammonia in ambient water was augmented by an an increase in pH. The possible causation and ecological significance of these effects are discussed. There are indications that the snails are physiologically well-adapted to utilize ammonia when required and also to control its excretion and uptake from the medium.", "contents": "The chemical ecology of Biomphalaria glabrata: the effects of ammonia on the growth rate of juvenile snails. When juvenile specimens of Biomphalaria glabrata were subjected to concentrations of ammonia ranging from 1-100 mug/ml in various media the following effects were observed: the addition of ammonia to borate buffered media caused mortality. Both borate and tris-buffered media caused a decrease in the growth rate of snails when compared with controls in SSW. The growth rates of the snails could be enhanced by increasing the concentration of ammonia to critical thresholds, but further increases beyond these thresholds resulted in growth inhibition. The toxicity of ammonia in ambient water was augmented by an an increase in pH. The possible causation and ecological significance of these effects are discussed. There are indications that the snails are physiologically well-adapted to utilize ammonia when required and also to control its excretion and uptake from the medium."}
{"id": "PMID:10015", "title": "[Spectral effects of denaturation of B- and C-phycoerythrins].", "content": "B-phycoerythrin (B-PhE) from red alga Porphyridium cruentum and C-phycoerythrin (C-PhE) from blue-green alga Nostoc punctiforma were isolated. Their absorption and fluorescence spectra were measured at room and liquid nitrogen temperature. The drastic change of fluorescence and absorption maxima under dissociation of the proteins into subunits was observed. Dissociation of the C-PhE into two subunits (molecular weight 16 000 and 12 000) was revealed by SDS-acrylamide gel electrophoresis in 0.01% SDS solution at pH 7.0. The absorption spectra of subunits of both B-PhE and C-PhE were similar. The fluorescence quenching by oxidants and destructive photooxidation were negligible and increased after denaturation.", "contents": "[Spectral effects of denaturation of B- and C-phycoerythrins]. B-phycoerythrin (B-PhE) from red alga Porphyridium cruentum and C-phycoerythrin (C-PhE) from blue-green alga Nostoc punctiforma were isolated. Their absorption and fluorescence spectra were measured at room and liquid nitrogen temperature. The drastic change of fluorescence and absorption maxima under dissociation of the proteins into subunits was observed. Dissociation of the C-PhE into two subunits (molecular weight 16 000 and 12 000) was revealed by SDS-acrylamide gel electrophoresis in 0.01% SDS solution at pH 7.0. The absorption spectra of subunits of both B-PhE and C-PhE were similar. The fluorescence quenching by oxidants and destructive photooxidation were negligible and increased after denaturation."}
{"id": "PMID:10016", "title": "[Catalytic properties and stability of horseradish peroxidase immobilized in polyacrylamide gel].", "content": "Effect of polyacrylamide (PAA) gel on properties of horseradish peroxidase, immobilized by means of the incorporation into PAA gel is studied. Catalytic properties of immobilized enzyme are studied. Km value and pH-dependency of the enzyme activity are found to be close to those of soluble enzyme, kcat value is 3 times lower at pH 7.0. PH-stability of immobilized peroxidase at 20 degrees C and thermostability of soluble and immobilized peroxidases at pH 7.0 within the temperature range from 20 to 81 degrees C are studied. The stability of peroxidase in PAA gel is found to decrease (in 3 times at 20 degrees C, and in 17 times at 56 degrees C). A mechanism of the effect of PAA gel on catalytic properties and stability of peroxidase is discussed.", "contents": "[Catalytic properties and stability of horseradish peroxidase immobilized in polyacrylamide gel]. Effect of polyacrylamide (PAA) gel on properties of horseradish peroxidase, immobilized by means of the incorporation into PAA gel is studied. Catalytic properties of immobilized enzyme are studied. Km value and pH-dependency of the enzyme activity are found to be close to those of soluble enzyme, kcat value is 3 times lower at pH 7.0. PH-stability of immobilized peroxidase at 20 degrees C and thermostability of soluble and immobilized peroxidases at pH 7.0 within the temperature range from 20 to 81 degrees C are studied. The stability of peroxidase in PAA gel is found to decrease (in 3 times at 20 degrees C, and in 17 times at 56 degrees C). A mechanism of the effect of PAA gel on catalytic properties and stability of peroxidase is discussed."}
{"id": "PMID:10017", "title": "Acid-base changes of mature and premature neonates following exchange transfusion.", "content": "The changes of acid-base values of 60 mature and premature neonates treated by exchange transfusion were followed. It could be shown that the blood conserves having acidic pH values caused no acidosis if the acid-base balance of the patients had been normal before transfusion. An existing acidosis frequently increased significantly in the first day of life of the mature but also in the later days in premature neonates. Thus, the determination of acid-base state prior and after transfusion of such patients seems to be important. In the case of pronounced acidosis its correction and also the control of the acid-base values after the exchange transfusion are necessary.", "contents": "Acid-base changes of mature and premature neonates following exchange transfusion. The changes of acid-base values of 60 mature and premature neonates treated by exchange transfusion were followed. It could be shown that the blood conserves having acidic pH values caused no acidosis if the acid-base balance of the patients had been normal before transfusion. An existing acidosis frequently increased significantly in the first day of life of the mature but also in the later days in premature neonates. Thus, the determination of acid-base state prior and after transfusion of such patients seems to be important. In the case of pronounced acidosis its correction and also the control of the acid-base values after the exchange transfusion are necessary."}
{"id": "PMID:10019", "title": "Active enzyme gel chromatography. I. Experimental aspects.", "content": "Transport properties of active enzyme species can be studied effectively by layering a small band of enzyme-containing sample on a gel chromatographic column previously saturated with substrate. The column is optically scanned at successive time intervals to yield profiles representing the appearance of chromophoric product or disappearnce of chromophoric substrate. These profiles permit determination of the specific activity and rate of transport of the active species. Initial studies on mechanic of the technique establish the feasibility of accurately determining transport properties of active enzyme species chromatographed on gel columns. Illustrative results are presented for L-glutamate dehydrogenase and for homoserine dehydrogenase studied in both forward and reverse reactions. It is shown that the partititon cross sections derived from the rates of motion of catalytic activity are the same as those determined by equilibrium saturation experiments which directly measure the degree of partitioning by the protein. These results establish the validity of the technique for a variety of future studies. Active enzyme gel chromatography appears comparable in precision to the active enzyme sedimentation technique at current stages of development.", "contents": "Active enzyme gel chromatography. I. Experimental aspects. Transport properties of active enzyme species can be studied effectively by layering a small band of enzyme-containing sample on a gel chromatographic column previously saturated with substrate. The column is optically scanned at successive time intervals to yield profiles representing the appearance of chromophoric product or disappearnce of chromophoric substrate. These profiles permit determination of the specific activity and rate of transport of the active species. Initial studies on mechanic of the technique establish the feasibility of accurately determining transport properties of active enzyme species chromatographed on gel columns. Illustrative results are presented for L-glutamate dehydrogenase and for homoserine dehydrogenase studied in both forward and reverse reactions. It is shown that the partititon cross sections derived from the rates of motion of catalytic activity are the same as those determined by equilibrium saturation experiments which directly measure the degree of partitioning by the protein. These results establish the validity of the technique for a variety of future studies. Active enzyme gel chromatography appears comparable in precision to the active enzyme sedimentation technique at current stages of development."}
{"id": "PMID:10020", "title": "A calorimetric study of polyguanylic acid at neutral pH.", "content": "The structure of polyguanylic acid (poly G) at neutral pH has been studied by optical and calorimetrical methods. It can be shown that diverging from earlier findings Poly G reversibly undergoes a cooperative thermal transition. Thermal denaturation curves are recorded at 253 nm as a function of the sodium ion concentration. The denaturation enthalpy of poly G in dilute aqueous solution is determined to 2.2 kcal/mole g. It is concluded, that the part of the ordered poly G structure, which gives rise to a temperature dependent cooperative transition, arises from stacking interactions of adjacent bases in the single strand.", "contents": "A calorimetric study of polyguanylic acid at neutral pH. The structure of polyguanylic acid (poly G) at neutral pH has been studied by optical and calorimetrical methods. It can be shown that diverging from earlier findings Poly G reversibly undergoes a cooperative thermal transition. Thermal denaturation curves are recorded at 253 nm as a function of the sodium ion concentration. The denaturation enthalpy of poly G in dilute aqueous solution is determined to 2.2 kcal/mole g. It is concluded, that the part of the ordered poly G structure, which gives rise to a temperature dependent cooperative transition, arises from stacking interactions of adjacent bases in the single strand."}
{"id": "PMID:10021", "title": "Electron transport by C-type cytochromes. I. The reaction of horse heart cytochrome c with anionic reductants.", "content": "The kinetics of reduction of horse heartcytochrome c have been investigated using the reductants sodium dithionite and potassium ferrocyanide. Sodium dithionite reduction at pH 7.0 yields rate constants of 2.8 X 10(8)M(-1)sec-1 for SO2 AND 6 X 10(5) M-1 sec-1 for S2O4 at infinite dilution. Moreover, the data presented demonstrates the participation of positively charged amino acid side chains at the site of electron transfer. The effect of pH on the reduction of ferricytochrome c requires a minimum of two pK values for description (pK1 = 7.0 +/- 0.4, pK2 = 9.3 +/- 0.3). Based on the pK values determined, one or more lysines and a residues(s) with a low pK are implicated as the positively charged residues participating in electron transfer. From a comparison of the rates of reduction of various denatured forms of cytochrome c we feel that the most viable conclusion is that electron transfer takes place at the exposed heme edge in the vicinity of the amino acid side chains indicated above. Ferrocyanide reduction of ferri-horse heart cytochrome c takes place in a kinetically complex manner. A mechanism is described which includes complexes of ferrocyanide and ferricytochrome c and ferricyanide and ferrocytochrome c. As was found for dithionite reduction a positively charged region of the cytochrome c participates in electron transfer. Combining our results with ferrocyanide and dithionite we conclude that avaible data is compatible with a single mechanism of electron transfer. It is suggested that the kinetic distinction between different reductants lies in the lifetime of the transient complex formed, with the order ferrocyanide greater than S2O4 greater than SO2.", "contents": "Electron transport by C-type cytochromes. I. The reaction of horse heart cytochrome c with anionic reductants. The kinetics of reduction of horse heartcytochrome c have been investigated using the reductants sodium dithionite and potassium ferrocyanide. Sodium dithionite reduction at pH 7.0 yields rate constants of 2.8 X 10(8)M(-1)sec-1 for SO2 AND 6 X 10(5) M-1 sec-1 for S2O4 at infinite dilution. Moreover, the data presented demonstrates the participation of positively charged amino acid side chains at the site of electron transfer. The effect of pH on the reduction of ferricytochrome c requires a minimum of two pK values for description (pK1 = 7.0 +/- 0.4, pK2 = 9.3 +/- 0.3). Based on the pK values determined, one or more lysines and a residues(s) with a low pK are implicated as the positively charged residues participating in electron transfer. From a comparison of the rates of reduction of various denatured forms of cytochrome c we feel that the most viable conclusion is that electron transfer takes place at the exposed heme edge in the vicinity of the amino acid side chains indicated above. Ferrocyanide reduction of ferri-horse heart cytochrome c takes place in a kinetically complex manner. A mechanism is described which includes complexes of ferrocyanide and ferricytochrome c and ferricyanide and ferrocytochrome c. As was found for dithionite reduction a positively charged region of the cytochrome c participates in electron transfer. Combining our results with ferrocyanide and dithionite we conclude that avaible data is compatible with a single mechanism of electron transfer. It is suggested that the kinetic distinction between different reductants lies in the lifetime of the transient complex formed, with the order ferrocyanide greater than S2O4 greater than SO2."}
{"id": "PMID:10022", "title": "Flash photometric experiments on the photochemical cycle of bacteriorhodopsin.", "content": "The photochemical reaction cycle of bacteriorhodopsin was investigated by means of flash photometric methods. Three different intermediates with absorption maxima at about 630 nm, 411 nm, and 646 nm could be detected. Kinetic data of the occurrence of these intermediates were obtained from isolated purple membrane in different mediums and from intact halobacteria. An activation energy of 14.1 +/- 0.4 kcal-mol-1 and of about 19 kcal-mol-1 for formation of bacteriorhodopsin 411 and of bacteriorhodopsin 565, resp., was calculated. pH-changes in the medium caused by the reaction cycle of bacteriorhodopsin were detected by use of the pH-indicator bromocresol green.", "contents": "Flash photometric experiments on the photochemical cycle of bacteriorhodopsin. The photochemical reaction cycle of bacteriorhodopsin was investigated by means of flash photometric methods. Three different intermediates with absorption maxima at about 630 nm, 411 nm, and 646 nm could be detected. Kinetic data of the occurrence of these intermediates were obtained from isolated purple membrane in different mediums and from intact halobacteria. An activation energy of 14.1 +/- 0.4 kcal-mol-1 and of about 19 kcal-mol-1 for formation of bacteriorhodopsin 411 and of bacteriorhodopsin 565, resp., was calculated. pH-changes in the medium caused by the reaction cycle of bacteriorhodopsin were detected by use of the pH-indicator bromocresol green."}
{"id": "PMID:10024", "title": "A new alkali-resistant hemoglobin alpha2J Oxford gammaF2 in a Sicilian baby girl with homozygous beta0 thalassemia.", "content": "A 10-mo-old baby girl with homozygous beta0 thalassemia and alphaJOxford, presenting the clinical picture of homozygous beta thalassemia is described. Hemoglobin electrophoresis showed three bands: the first two with the mobilities of hemoglobin Hb A2 (1%) and Hb F (69%), respectively, the third migrating a little faster than Hb A (30%). About 30% of her alpha chains were J Oxford which, bound to her gamma chains, produced a new alkali-resistant hemoglobin, alpha2 J Oxford gamma F2, which has not been described previously. Hemoglobin synthesis in vitro showed the absence of beta chain synthesis and an alpha/non-alpha ratio of 2. The patient's father was heterozygous for both the Hb J Oxford and beta0 thalassemia genes, the mother a carrier of beta0 thalassemia; four other relatives were carriers of Hb J Oxford, and one was a carrier of beta thalassemia.", "contents": "A new alkali-resistant hemoglobin alpha2J Oxford gammaF2 in a Sicilian baby girl with homozygous beta0 thalassemia. A 10-mo-old baby girl with homozygous beta0 thalassemia and alphaJOxford, presenting the clinical picture of homozygous beta thalassemia is described. Hemoglobin electrophoresis showed three bands: the first two with the mobilities of hemoglobin Hb A2 (1%) and Hb F (69%), respectively, the third migrating a little faster than Hb A (30%). About 30% of her alpha chains were J Oxford which, bound to her gamma chains, produced a new alkali-resistant hemoglobin, alpha2 J Oxford gamma F2, which has not been described previously. Hemoglobin synthesis in vitro showed the absence of beta chain synthesis and an alpha/non-alpha ratio of 2. The patient's father was heterozygous for both the Hb J Oxford and beta0 thalassemia genes, the mother a carrier of beta0 thalassemia; four other relatives were carriers of Hb J Oxford, and one was a carrier of beta thalassemia."}
{"id": "PMID:10025", "title": "Effect of osmotic pressure, ionic strength and dibutyryl cyclic adenosine monophosphate on the adhesion of hen erythrocytes.", "content": "In the presence of lysolecithin at physiological pH it was found that the increase of ionic strength facilitates the adhesion of hen erythrocytes. In this medium, dibutyryl cyclic adenosine monophosphate (DBcAMP) increases the adhesion index of the cells. If the osmotic pressure is elevated without a proper increase of ionic strength, the lysolecithin induced hemolysis and adhesion are found to be lacking.", "contents": "Effect of osmotic pressure, ionic strength and dibutyryl cyclic adenosine monophosphate on the adhesion of hen erythrocytes. In the presence of lysolecithin at physiological pH it was found that the increase of ionic strength facilitates the adhesion of hen erythrocytes. In this medium, dibutyryl cyclic adenosine monophosphate (DBcAMP) increases the adhesion index of the cells. If the osmotic pressure is elevated without a proper increase of ionic strength, the lysolecithin induced hemolysis and adhesion are found to be lacking."}
{"id": "PMID:10028", "title": "Report of the first hemispheric meeting on meningococcal disease.", "content": "The first Hemispheric meeting on meningococcal meningitis was held in S\u00e3o Paulo and Bras\u00edlia on 23-28 February 1976. Organized by the Pan American Health Organization in collaboration with the Government of Brazil and other PAHO Member States, the meeting had three principal aims: to review the general subject of cerebrospinal meningitis and the special situation in Brazil; to analyze experience gained in Brazil regarding laboratory diagnosis, treatment, and reduction of mortality among hospitalized patients; and to develop prevention and control strategies based on a review of available scientific knowledge and techniques for prevention and control of meningococcal disease.", "contents": "Report of the first hemispheric meeting on meningococcal disease. The first Hemispheric meeting on meningococcal meningitis was held in S\u00e3o Paulo and Bras\u00edlia on 23-28 February 1976. Organized by the Pan American Health Organization in collaboration with the Government of Brazil and other PAHO Member States, the meeting had three principal aims: to review the general subject of cerebrospinal meningitis and the special situation in Brazil; to analyze experience gained in Brazil regarding laboratory diagnosis, treatment, and reduction of mortality among hospitalized patients; and to develop prevention and control strategies based on a review of available scientific knowledge and techniques for prevention and control of meningococcal disease."}
{"id": "PMID:10029", "title": "The contribution of extraneuronal uptake to the trachea-blood vessel selectivity of beta-adrenoceptor stimulants in vitro in guinea-pigs.", "content": "1 The potencies relative to isoprenaline of isoetharine, tertiary butyl noradrenaline, salbutamol, orciprenaline, Me 506, rimiterol, fenoterol, carbuterol and terbutaline on isolated preparations of guinea-pig trachea and blood vessels (perfused hind limb) were determined. All the compounds were selective for trachea and selectivity values, i.e. relative potency on trachea divided by relative potency on hind limb, ranged from 2.3 to 21.4. 2 Responses to isoprenaline (the reference compound), tertiary butyl noradrenaline and isoetharine were potentiated on trachea by 50 muM phenoxybenzamine (PHB) and by other inhibitors of extraneuronal uptake (ENU). Under these conditions the selectivity values of all the compounds was close to unity. 3 Selectivity values were also close to unity if they were calculated from data obtained without ENU inhibition, provided that only those compounds not potentiated by PHB on trachea were used. 4 It is proposed that the trachea-blood vessel selectivity shown by beta-adrenoceptor stimulants can be caused by the influence of ENU upon them, rather than by their ability to distinguish between two beta2-adrenoceptors. 5 The suggestion that differences exist between beta2-adrenoceptors in respiratory and vascular smooth muscle is not supported by the in vitro experiments described.", "contents": "The contribution of extraneuronal uptake to the trachea-blood vessel selectivity of beta-adrenoceptor stimulants in vitro in guinea-pigs. 1 The potencies relative to isoprenaline of isoetharine, tertiary butyl noradrenaline, salbutamol, orciprenaline, Me 506, rimiterol, fenoterol, carbuterol and terbutaline on isolated preparations of guinea-pig trachea and blood vessels (perfused hind limb) were determined. All the compounds were selective for trachea and selectivity values, i.e. relative potency on trachea divided by relative potency on hind limb, ranged from 2.3 to 21.4. 2 Responses to isoprenaline (the reference compound), tertiary butyl noradrenaline and isoetharine were potentiated on trachea by 50 muM phenoxybenzamine (PHB) and by other inhibitors of extraneuronal uptake (ENU). Under these conditions the selectivity values of all the compounds was close to unity. 3 Selectivity values were also close to unity if they were calculated from data obtained without ENU inhibition, provided that only those compounds not potentiated by PHB on trachea were used. 4 It is proposed that the trachea-blood vessel selectivity shown by beta-adrenoceptor stimulants can be caused by the influence of ENU upon them, rather than by their ability to distinguish between two beta2-adrenoceptors. 5 The suggestion that differences exist between beta2-adrenoceptors in respiratory and vascular smooth muscle is not supported by the in vitro experiments described."}
{"id": "PMID:10034", "title": "Adrenoreceptors of the guinea-pig urinary bladder.", "content": "1 Adrenaline, noradrenaline and isoprenaline (5 mug/ml) did not affect the resting tone of the isolated urinary bladder of the guinea-pig. 2 The catecholamines (1-2 mug/ml) inhibited neuronally evoked contractions at various stimulation frequencies; the inhibition was maximum at 2 Hz and minimum at 50 Hz. Isoprenaline produced maximum inhibition. 3 Propranolol (0.5 mug/ml) completely blocked the catecholamine-induced inhibition at all the frequencies employed. The concentration-response curves of isoprenaline at 2, 10 and 50 Hz were characteristically shifted by propranolol (50 ng/ml). Phenoxybenzamine (0.2 mug/ml) was totally ineffective. 4 In some experiments adrenaline significantly raised the tone of the bladder exposed to propranolol; this effect could be blocked by phenoxybenzamine. 5 Acetylcholine-induced bladder contractions were inhibited by adrenaline (2 mug/ml); the inhibition was completely blocked by propranolol (0.5 mug/ml). 6 The results indicate the presence of an inhibitory beta-adrenoceptor and suggest the possibility of an excitatory alpha-adrenoceptor in guinea-pig urinary bladder.", "contents": "Adrenoreceptors of the guinea-pig urinary bladder. 1 Adrenaline, noradrenaline and isoprenaline (5 mug/ml) did not affect the resting tone of the isolated urinary bladder of the guinea-pig. 2 The catecholamines (1-2 mug/ml) inhibited neuronally evoked contractions at various stimulation frequencies; the inhibition was maximum at 2 Hz and minimum at 50 Hz. Isoprenaline produced maximum inhibition. 3 Propranolol (0.5 mug/ml) completely blocked the catecholamine-induced inhibition at all the frequencies employed. The concentration-response curves of isoprenaline at 2, 10 and 50 Hz were characteristically shifted by propranolol (50 ng/ml). Phenoxybenzamine (0.2 mug/ml) was totally ineffective. 4 In some experiments adrenaline significantly raised the tone of the bladder exposed to propranolol; this effect could be blocked by phenoxybenzamine. 5 Acetylcholine-induced bladder contractions were inhibited by adrenaline (2 mug/ml); the inhibition was completely blocked by propranolol (0.5 mug/ml). 6 The results indicate the presence of an inhibitory beta-adrenoceptor and suggest the possibility of an excitatory alpha-adrenoceptor in guinea-pig urinary bladder."}
{"id": "PMID:10035", "title": "The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea.", "content": "1 A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat. 2 The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2alpha, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2alpha and did not exhibit an intrinsic tone. 3 (-)-Isoprenaline and (-)-adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (+/-)-noradrenaline in the lung strip was isoprenaline greater than adrenaline greater than noradrenaline but in the trachea was isoprenaline greater than noradrenaline greater than or equal to adrenaline. 4 beta2-Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting beta2-adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of beta2-adrenoceptors in lung strip and beta1-adrenoceptors in trachea. 5 Strong Schultz-Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine-treated lung strip and trachea was not due to prostaglandins E1, F2alpha or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS-A). 6 It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs.", "contents": "The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea. 1 A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat. 2 The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2alpha, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2alpha and did not exhibit an intrinsic tone. 3 (-)-Isoprenaline and (-)-adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (+/-)-noradrenaline in the lung strip was isoprenaline greater than adrenaline greater than noradrenaline but in the trachea was isoprenaline greater than noradrenaline greater than or equal to adrenaline. 4 beta2-Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting beta2-adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of beta2-adrenoceptors in lung strip and beta1-adrenoceptors in trachea. 5 Strong Schultz-Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine-treated lung strip and trachea was not due to prostaglandins E1, F2alpha or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS-A). 6 It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs."}
{"id": "PMID:10036", "title": "Imaginal flooding and exposure to real phobic situations: treatment outcome with agoraphobic patients.", "content": "Each of thirty-six female agoraphobic out-patients were treated by one of three methods: 8 sessions of imaginal flooding followed by 8 sessions of practice in the real situation; 16 sessions of combined flooding and practice; or 16 sessions of practice alone. Three therapists treated equal numbers of patients in each group, and there was some evidence that patients' response varied according to the therapist seen, irrespective of treatment group. There were no significant differences between treatment groups after 8 sessions, 16 sessions or on six-month follow-up. It is concluded that there are no long-term differences between the effects of treatments involving exposure to either imaginal or real phobic situations or to a combination of both, provided that patients are encouraged to practise between sessions.", "contents": "Imaginal flooding and exposure to real phobic situations: treatment outcome with agoraphobic patients. Each of thirty-six female agoraphobic out-patients were treated by one of three methods: 8 sessions of imaginal flooding followed by 8 sessions of practice in the real situation; 16 sessions of combined flooding and practice; or 16 sessions of practice alone. Three therapists treated equal numbers of patients in each group, and there was some evidence that patients' response varied according to the therapist seen, irrespective of treatment group. There were no significant differences between treatment groups after 8 sessions, 16 sessions or on six-month follow-up. It is concluded that there are no long-term differences between the effects of treatments involving exposure to either imaginal or real phobic situations or to a combination of both, provided that patients are encouraged to practise between sessions."}
{"id": "PMID:10037", "title": "Imaginal flooding and exposure to real phobic situations: changes during treatment.", "content": "This paper reports the results of measures taken during treatment in the study of imaginal flooding and exposure to real phobic situations previously described by Mathews, Johnston, Lancashire, Munby, Shaw and Gelder (1976). On weekly measures of change of similar reduction in phobic behaviour in all treatments was found, confirming the previous findings. Differences in therapist effectiveness were also confirmed. On measures of the immediate effects of treatment, exposure to the phobic situation had consistent positive effects, imaginal flooding had little or no detectable effect. It is proposed that the treatments studied differ in their immediate effects on phobic behaviour but also have the common effect of facilitating counterphobic behaviour outside the treatment situation, and that this is the main agent of therapeutic change.", "contents": "Imaginal flooding and exposure to real phobic situations: changes during treatment. This paper reports the results of measures taken during treatment in the study of imaginal flooding and exposure to real phobic situations previously described by Mathews, Johnston, Lancashire, Munby, Shaw and Gelder (1976). On weekly measures of change of similar reduction in phobic behaviour in all treatments was found, confirming the previous findings. Differences in therapist effectiveness were also confirmed. On measures of the immediate effects of treatment, exposure to the phobic situation had consistent positive effects, imaginal flooding had little or no detectable effect. It is proposed that the treatments studied differ in their immediate effects on phobic behaviour but also have the common effect of facilitating counterphobic behaviour outside the treatment situation, and that this is the main agent of therapeutic change."}
{"id": "PMID:10038", "title": "Fresh symptom emergence after intensive behaviour therapy.", "content": "The outcome of a standard four-day intensive symptomatic treatment programme with 39 agoraphobics is examined in relation to the incidence of fresh symptom emergence. Twenty-six patients suffered fresh symptom emergence during follow-up, and there was a significant association of fresh symptom emergence with poorer outcome at one-year follow-up. About 18 percent of patients were adversely affected by the treatment programme, as judged on a wide range of symptoms and measures of inter- and intra-personal adjustment. Sixteen individually treated patients are then compared with the 39 group-treated patients and differences in drop-out rate are discussed.", "contents": "Fresh symptom emergence after intensive behaviour therapy. The outcome of a standard four-day intensive symptomatic treatment programme with 39 agoraphobics is examined in relation to the incidence of fresh symptom emergence. Twenty-six patients suffered fresh symptom emergence during follow-up, and there was a significant association of fresh symptom emergence with poorer outcome at one-year follow-up. About 18 percent of patients were adversely affected by the treatment programme, as judged on a wide range of symptoms and measures of inter- and intra-personal adjustment. Sixteen individually treated patients are then compared with the 39 group-treated patients and differences in drop-out rate are discussed."}
{"id": "PMID:10039", "title": "Personality, expectancies and group psychotherapy.", "content": "The paper reports an extension of work into the relevance of personality and pre-treatment expectancies for allocation and response of patients to group psychotherapy. The results show that subjects who are internally directed in interest and who have a liberal attitude to a variety of social issues and a \"psychological\" set to treatment are more responsive to group psychotherapy as seen by their therapists as well as by themselves. Those who are externally directed in interest and who have a conservative attitude to life and a more \"medical-physical\" set to treatment are more likely to be referred for behaviour therapy; if referred for group psychotherapy they are likely either to drop out or to show very limited response to treatment.", "contents": "Personality, expectancies and group psychotherapy. The paper reports an extension of work into the relevance of personality and pre-treatment expectancies for allocation and response of patients to group psychotherapy. The results show that subjects who are internally directed in interest and who have a liberal attitude to a variety of social issues and a \"psychological\" set to treatment are more responsive to group psychotherapy as seen by their therapists as well as by themselves. Those who are externally directed in interest and who have a conservative attitude to life and a more \"medical-physical\" set to treatment are more likely to be referred for behaviour therapy; if referred for group psychotherapy they are likely either to drop out or to show very limited response to treatment."}
{"id": "PMID:10049", "title": "Further characterization of morphine-like peptides (endorphins) from pituitary.", "content": "Pituitary peptides with opioid pharmacologic action (endorphins) can exist in several forms with different basicities and molecular weights from about 3000 to less than 1000 daltons. Partial purification yielded an endorphin at least 4 times more potent than normorphine and 16 times more potent than the endogenous brain pentapeptide methionine enkephalin. It is proposed that pituitary endorphin or a similar peptide in brain may be the precursor of brain enkephalin.", "contents": "Further characterization of morphine-like peptides (endorphins) from pituitary. Pituitary peptides with opioid pharmacologic action (endorphins) can exist in several forms with different basicities and molecular weights from about 3000 to less than 1000 daltons. Partial purification yielded an endorphin at least 4 times more potent than normorphine and 16 times more potent than the endogenous brain pentapeptide methionine enkephalin. It is proposed that pituitary endorphin or a similar peptide in brain may be the precursor of brain enkephalin."}
{"id": "PMID:10050", "title": "Separately developing axonal uptake of 5-hydroxytryptamine and norepinephrine in the fetal ileum of the rabbit.", "content": "Uptake of 5-hydroxytryptamine (5-HT) by adult and fetal rabbit's ileum was studied. The adult myenteric plexus accumulated tritium when incubated with tritiated 5-HT. However, in addition to labeled 5-HT, tritiated 5-hydroxyindole acetic acid and, when monoamine oxidase (MAO) was inhibited, 5-HT-o-glucuronide were found in the tissue. Two uptake processes differing in affinity could be defined. Only the high affinity process was saturable. Fetal ileum took up tritiated 5-HT but glucuronidation did not occur when MAO was inhibited. The uptake of tritiated 5-HT by the fetal ileum was due to a single, saturable, temperature sensitive (Q10 at 27-37 degress C = 2.4) process inhibited by ouabain. It was identical to the high affinity uptake found in adult tissue. This specific high affinity uptake could be found as early as the 16th day of gestation, 5-8 days before uptake of norepinephrine (NE) begins. Light and electron microscope radioautography revealed that the uptake of 5-HT was primarily into axons and a characteristic structure called the expanded process, both in the myenteric plexus. Both contained dense-cored vesicles. Axons were not labeled by tritiated NE until after 24 days and the expanded process was never labeled by tritiated NE. This study shows that uptake of 5-HT is a property of distinct system of axons in the mammalian myenteric plexus which develops prior to adrenergic axons during ontogeny.", "contents": "Separately developing axonal uptake of 5-hydroxytryptamine and norepinephrine in the fetal ileum of the rabbit. Uptake of 5-hydroxytryptamine (5-HT) by adult and fetal rabbit's ileum was studied. The adult myenteric plexus accumulated tritium when incubated with tritiated 5-HT. However, in addition to labeled 5-HT, tritiated 5-hydroxyindole acetic acid and, when monoamine oxidase (MAO) was inhibited, 5-HT-o-glucuronide were found in the tissue. Two uptake processes differing in affinity could be defined. Only the high affinity process was saturable. Fetal ileum took up tritiated 5-HT but glucuronidation did not occur when MAO was inhibited. The uptake of tritiated 5-HT by the fetal ileum was due to a single, saturable, temperature sensitive (Q10 at 27-37 degress C = 2.4) process inhibited by ouabain. It was identical to the high affinity uptake found in adult tissue. This specific high affinity uptake could be found as early as the 16th day of gestation, 5-8 days before uptake of norepinephrine (NE) begins. Light and electron microscope radioautography revealed that the uptake of 5-HT was primarily into axons and a characteristic structure called the expanded process, both in the myenteric plexus. Both contained dense-cored vesicles. Axons were not labeled by tritiated NE until after 24 days and the expanded process was never labeled by tritiated NE. This study shows that uptake of 5-HT is a property of distinct system of axons in the mammalian myenteric plexus which develops prior to adrenergic axons during ontogeny."}
{"id": "PMID:10051", "title": "A comparison of the 12,000 dalton proteins synthesized by Aplysia neurons L11 and R15.", "content": "The 12,000 dalton proteins of neurons L11 and R15 of the Aplysia abdominal ganglion were labeled by incubation of the ganglion in [3H]leucine and compared in terms of their subcellular localization, solubility in various media, and molecular charge. Both proteins are cytoplasmic constituents. Their solubility behavior is identical: both are insoluble in aqueous media of low and high ionic strength as well as chloroform-methanol, and both are solubilized by Triton X-100 + urea and by LIS. They are essentially identical in molecular weight as determined by SDS gel electrophoresis but differ by a single charge per molecule at low pH. The broad similarity between these proteins suggests that they could serve similar functions, while the observed charge difference might be important in terms of previously discovered differences in their processing.", "contents": "A comparison of the 12,000 dalton proteins synthesized by Aplysia neurons L11 and R15. The 12,000 dalton proteins of neurons L11 and R15 of the Aplysia abdominal ganglion were labeled by incubation of the ganglion in [3H]leucine and compared in terms of their subcellular localization, solubility in various media, and molecular charge. Both proteins are cytoplasmic constituents. Their solubility behavior is identical: both are insoluble in aqueous media of low and high ionic strength as well as chloroform-methanol, and both are solubilized by Triton X-100 + urea and by LIS. They are essentially identical in molecular weight as determined by SDS gel electrophoresis but differ by a single charge per molecule at low pH. The broad similarity between these proteins suggests that they could serve similar functions, while the observed charge difference might be important in terms of previously discovered differences in their processing."}
{"id": "PMID:10055", "title": "[Consequences of the administration of alpha or beta drenolytic agents on the mobilization of plasma free fatty acids as induced by noradrenaline and isoprenaline in the dog].", "content": "Noradr\u00e9naline or isoprenaline (a beta sympathicomimetic drug) infusion in fasting awake dog provoque a rise of plasmatic FFA. This effect is abolished by administration of propranolol (beta blocking agent) but not by phentolamine (alpha blocking agent). Phentolamine potentiate the rise of FFA in response to noradrenaline but not to isoprenaline. This alpha blocking drug supress the fall of FFA induced by phenylephrine a sympathomimetic drug.", "contents": "[Consequences of the administration of alpha or beta drenolytic agents on the mobilization of plasma free fatty acids as induced by noradrenaline and isoprenaline in the dog]. Noradr\u00e9naline or isoprenaline (a beta sympathicomimetic drug) infusion in fasting awake dog provoque a rise of plasmatic FFA. This effect is abolished by administration of propranolol (beta blocking agent) but not by phentolamine (alpha blocking agent). Phentolamine potentiate the rise of FFA in response to noradrenaline but not to isoprenaline. This alpha blocking drug supress the fall of FFA induced by phenylephrine a sympathomimetic drug."}
{"id": "PMID:10056", "title": "[Influence of variations in blood pH on the bronchodilator action of salbutamol and terbutaline].", "content": "In the cat, the broncho-dilatator effects of salbutamol and terbutaline are influenced by blood pH variations. Gazeous or metabolic alkalosis increases, acidosis decreases, the broncho-dilatation provoked by salbutamol or terbutaline.", "contents": "[Influence of variations in blood pH on the bronchodilator action of salbutamol and terbutaline]. In the cat, the broncho-dilatator effects of salbutamol and terbutaline are influenced by blood pH variations. Gazeous or metabolic alkalosis increases, acidosis decreases, the broncho-dilatation provoked by salbutamol or terbutaline."}
{"id": "PMID:10057", "title": "Effect of structural analogs of butaclamol (a new antipsychotic drug) on striatal homovanillic acid and adenyl cyclase of olfactory tubercle in rats.", "content": "The 3-isopropyl (I), 3-cyclohexyl (II) and 3-phenyl (III) analogs of the new antipsychotic drug butaclamol, which contains a 3-tertiary butyl group, and their respective (+)-enantiomers, but not (-)-enantiomers, caused a dose related elevation of rat striatal homovanillic acid concentration, indicative of an increased dopamine (DA) turnover; droperidol also exhibited this activity. The order of activity of the (+)-enantiomers was (butaclamol) approximately II greater than I greater than III. A decrease in striatal DA was observed with (+)-I and (+)-III at the highest dose used, but not at one-half the dose. Each analog antagonized the DA-induced increase in adenyl cyclase (EC 4.6.1.1) activity of olfactory tubercle homogenates, the order of activity of the racemates (except for II) AND (+)-ENANTIOMERS BEING (BUTACLAMOL) APPROXIMATELY I greater than III greater than II. The (+)-enantiomers of butaclamol and analogs were two to four times more potent than their respective racemates, with (+)-butaclamol and (+)-I displaying activity generally equivalent to fluphenazine. The respective (-)-enantiomers were ineffective indicating a stereochemical specificity for DA-receptor blockade. Such analogs presented should be of value in elucidating dopaminergic mechansims.", "contents": "Effect of structural analogs of butaclamol (a new antipsychotic drug) on striatal homovanillic acid and adenyl cyclase of olfactory tubercle in rats. The 3-isopropyl (I), 3-cyclohexyl (II) and 3-phenyl (III) analogs of the new antipsychotic drug butaclamol, which contains a 3-tertiary butyl group, and their respective (+)-enantiomers, but not (-)-enantiomers, caused a dose related elevation of rat striatal homovanillic acid concentration, indicative of an increased dopamine (DA) turnover; droperidol also exhibited this activity. The order of activity of the (+)-enantiomers was (butaclamol) approximately II greater than I greater than III. A decrease in striatal DA was observed with (+)-I and (+)-III at the highest dose used, but not at one-half the dose. Each analog antagonized the DA-induced increase in adenyl cyclase (EC 4.6.1.1) activity of olfactory tubercle homogenates, the order of activity of the racemates (except for II) AND (+)-ENANTIOMERS BEING (BUTACLAMOL) APPROXIMATELY I greater than III greater than II. The (+)-enantiomers of butaclamol and analogs were two to four times more potent than their respective racemates, with (+)-butaclamol and (+)-I displaying activity generally equivalent to fluphenazine. The respective (-)-enantiomers were ineffective indicating a stereochemical specificity for DA-receptor blockade. Such analogs presented should be of value in elucidating dopaminergic mechansims."}
{"id": "PMID:10058", "title": "Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs.", "content": "To investigate the extent of cholinergic involvement in opiate-induced catalepsy, the effects of three anticholinergic drugs were studied on morphine-induced catalepsy. Haloperidol-induced catalepsy was also examined. Maximum catalepsy in rats was obtained with 30 mg/kg morphine or 3 mg/kg haloperidol. The anticholinergic drugs atropine, benztropine, and scopolamine were unable to antagonize morphine-induced catalepsy, yet readily antagonized haloperidol-induced catalepsy. Low doses of apomorphine (7.5 mg/kg), on the other hand, readily antagonized morphine catalepsy, but 13-fold higher doses of apomorphine were needed to block haloperidol-induced catalepsy. The results are compatible with the idea that catalepsy can be mediated via the striatum or the amygdala; morphine-dopamine antagonism may occur in the amygdala, whereas morphine-dopamine-cholinergic interactions occur in the striatum.", "contents": "Catalepsy induced by morphine or haloperidol: effects of apomorphine and anticholinergic drugs. To investigate the extent of cholinergic involvement in opiate-induced catalepsy, the effects of three anticholinergic drugs were studied on morphine-induced catalepsy. Haloperidol-induced catalepsy was also examined. Maximum catalepsy in rats was obtained with 30 mg/kg morphine or 3 mg/kg haloperidol. The anticholinergic drugs atropine, benztropine, and scopolamine were unable to antagonize morphine-induced catalepsy, yet readily antagonized haloperidol-induced catalepsy. Low doses of apomorphine (7.5 mg/kg), on the other hand, readily antagonized morphine catalepsy, but 13-fold higher doses of apomorphine were needed to block haloperidol-induced catalepsy. The results are compatible with the idea that catalepsy can be mediated via the striatum or the amygdala; morphine-dopamine antagonism may occur in the amygdala, whereas morphine-dopamine-cholinergic interactions occur in the striatum."}
{"id": "PMID:10059", "title": "Behavioral studies on the enantiomers of butaclamol demonstrating absolute optical specificity for neuroleptic activity.", "content": "Butaclamol is a member of a new chemical class for which antipsychotic activity in humans has been demonstrated. Butaclamol, a racemate, has been resolved into its optical isomers and a separation of activities was found to occur between the (+) and (-) enantiomers. The present experiments show that at doses ranging from 0.1 to 0.3 mg/kg the (+) enantiomer abolished amphetamine-induced (a) stereotyped behavior and (b) rotational behavior in rats with unilateral lesions in the substantia nigra. It also inhibited the lever-pressing response in the continuous (Sidman) avoidance procedure, blocked discriminated avoidance behavior, and decreased ambulation and rearing in the open field. In contrast, the (-) enantiomer was devoid of behavioral activity at 100-500 times larger doses. At considerably higher doses (+)-butaclamol antagonized epinephrine-induced mortality. Again, the (-)-butaclamol was devoid of this activity as well. The significance of absolute optical specifity manifested by a neuroleptic drug is discussed in the light of dopaminergic and adrenergic mechanisms.", "contents": "Behavioral studies on the enantiomers of butaclamol demonstrating absolute optical specificity for neuroleptic activity. Butaclamol is a member of a new chemical class for which antipsychotic activity in humans has been demonstrated. Butaclamol, a racemate, has been resolved into its optical isomers and a separation of activities was found to occur between the (+) and (-) enantiomers. The present experiments show that at doses ranging from 0.1 to 0.3 mg/kg the (+) enantiomer abolished amphetamine-induced (a) stereotyped behavior and (b) rotational behavior in rats with unilateral lesions in the substantia nigra. It also inhibited the lever-pressing response in the continuous (Sidman) avoidance procedure, blocked discriminated avoidance behavior, and decreased ambulation and rearing in the open field. In contrast, the (-) enantiomer was devoid of behavioral activity at 100-500 times larger doses. At considerably higher doses (+)-butaclamol antagonized epinephrine-induced mortality. Again, the (-)-butaclamol was devoid of this activity as well. The significance of absolute optical specifity manifested by a neuroleptic drug is discussed in the light of dopaminergic and adrenergic mechanisms."}
{"id": "PMID:10060", "title": "Effects of acidity, cations and alcoholic fractionation on absorption of heparin from gastrointestinal tract.", "content": "Heparin was introduced into the stomach or duodenum of mice separately in doses of ca. 250 mg/kg. A slight anticoagulant effect in the systemic circulation was detected in whole blood clotting times and factor X inhibition. In contrast to most drugs, more heparin was absorbed from the stomach than from the intestine. Suppressing ionization of heparin by simultaneous administration of acid resulted in improved absorption of heparin from the small intestine. Heparin was separated with ethanol into five molecular weight fraction: I, 17 999; II, 13 i99; III, 10800, IV, 8 700; and V, 6 700. Each was introduced into the duodenum of mice with citric acid. The maximum hypocoagulability was produced with fraction IV. When administered in distilled water instead of in citric acid, this heparin fraction did not produce an anticoagulant effect. These studies demonstrated that improvement of heparin absorption from the gastrointestinal tract can be obtained by the combination of suppressing ionization and selecting molecular size.", "contents": "Effects of acidity, cations and alcoholic fractionation on absorption of heparin from gastrointestinal tract. Heparin was introduced into the stomach or duodenum of mice separately in doses of ca. 250 mg/kg. A slight anticoagulant effect in the systemic circulation was detected in whole blood clotting times and factor X inhibition. In contrast to most drugs, more heparin was absorbed from the stomach than from the intestine. Suppressing ionization of heparin by simultaneous administration of acid resulted in improved absorption of heparin from the small intestine. Heparin was separated with ethanol into five molecular weight fraction: I, 17 999; II, 13 i99; III, 10800, IV, 8 700; and V, 6 700. Each was introduced into the duodenum of mice with citric acid. The maximum hypocoagulability was produced with fraction IV. When administered in distilled water instead of in citric acid, this heparin fraction did not produce an anticoagulant effect. These studies demonstrated that improvement of heparin absorption from the gastrointestinal tract can be obtained by the combination of suppressing ionization and selecting molecular size."}
{"id": "PMID:10061", "title": "Extracellular nuclease produced by a marine bacterium. II. Purification and properties of extracellular nuclease from a marine Vibrio sp.", "content": "Extracellular nuclease produced by a marine Vibrio sp., strain No. 2, was purified by salting out with ammonium sulfate and by chromatography on a DEAE-cellulose column and twice on a Sephadex G-200 column. The nuclease was eluted as a single peak in which the deoxyribonuclease (DNase) activity and ribonuclease (RNase) activity appeared together. Polyacrylamide disc gel electrophoresis showed a single band of stained protein which had both DNase and RNase activity. The molecular weight of the enzyme was estimated to be 100 000 daltons. When using partially purified enzyme from the DEAE-cellulose column, the optimum pH for activity was 8.0, and the enzyme was activated strongly by 0.05 M Mg2+ ions and stabilized by 0.01 M Ca2+ ion. These concentrations of Mg2+ and Ca2+ ions are similar to those of the two cations in seawater. Indeed, the enzyme revealed high activity and strong stability when kept in seawater. The presence of particulate matter, such as cellulose powder, chitin powder. Hyflosupercel, Kaolin, and marine mud increased the stability of the enzyme. When the hydrostatic pressure was increased from 1 to 1000 atmospheres, the decrements of the enzyme activity were more pronounced at 30 and 40 degrees C than at 25 or 50 degrees C. The enzyme activity was restored after decompression to 1 atm at 30 degrees C.", "contents": "Extracellular nuclease produced by a marine bacterium. II. Purification and properties of extracellular nuclease from a marine Vibrio sp. Extracellular nuclease produced by a marine Vibrio sp., strain No. 2, was purified by salting out with ammonium sulfate and by chromatography on a DEAE-cellulose column and twice on a Sephadex G-200 column. The nuclease was eluted as a single peak in which the deoxyribonuclease (DNase) activity and ribonuclease (RNase) activity appeared together. Polyacrylamide disc gel electrophoresis showed a single band of stained protein which had both DNase and RNase activity. The molecular weight of the enzyme was estimated to be 100 000 daltons. When using partially purified enzyme from the DEAE-cellulose column, the optimum pH for activity was 8.0, and the enzyme was activated strongly by 0.05 M Mg2+ ions and stabilized by 0.01 M Ca2+ ion. These concentrations of Mg2+ and Ca2+ ions are similar to those of the two cations in seawater. Indeed, the enzyme revealed high activity and strong stability when kept in seawater. The presence of particulate matter, such as cellulose powder, chitin powder. Hyflosupercel, Kaolin, and marine mud increased the stability of the enzyme. When the hydrostatic pressure was increased from 1 to 1000 atmospheres, the decrements of the enzyme activity were more pronounced at 30 and 40 degrees C than at 25 or 50 degrees C. The enzyme activity was restored after decompression to 1 atm at 30 degrees C."}
{"id": "PMID:10062", "title": "Ecological distribution of Spirillum lipoferum Beijerinck.", "content": "A survey in various countries revealed that the N2-fixing Spirillum lipoferum Beijerinck is a very common root and soil inhabitant in the tropics. More than half of the grass root and soil samples collected in tropical countries (four African countries and Brazil) contained abundant S. lipoferum populations, while less than 10% of the samples collected in temperate South Brazil, Kenya, and the U.S.A. contained the organism. There is a pronounced vegetation effect. Panicum maximum seems the most favorable among the forage grasses, while few positive samples were found under virgin tropical forest. Legume roots contained less S. lipoferum than adjacent soils. More than 80% of the samples from cereal roots (maize, sorghum, wheat, and rye) grown in fields fertilized with PK and Mo, in Rio de Janeiro State, were positive. Maize and sorghum grown under similar conditions in Wisconsin contained less than 10% of positive samples, but when maize fields were inoculated 90% of the root samples contained S. lipoferum. Alluvial soils were more favorable than eroded hill soils. Occurrence in soil was strongly pH-dependent with a pH around 7, being optimal (correlation coefficient r = 0.90). Sporadic occurrence was observed even in soils with pH 4.8. Surface-sterilized P. maximum roots collected from soils with pH ranging from 4.8 to 7.2 contained high S. lipoferum numbers which did not correlate with soil pH (r = 0.41). Amendment with malate of acid soils was not very effective in increasing nitrogenase (N2-ase) activity, but in two soils with pH above 6.4, high N2-ase activity was obtained after 16 to 48 h of incubation. In two soils from a temperate climate region, inoculation with S. lipoferum increased N2-ase activity produced through malate amendment.", "contents": "Ecological distribution of Spirillum lipoferum Beijerinck. A survey in various countries revealed that the N2-fixing Spirillum lipoferum Beijerinck is a very common root and soil inhabitant in the tropics. More than half of the grass root and soil samples collected in tropical countries (four African countries and Brazil) contained abundant S. lipoferum populations, while less than 10% of the samples collected in temperate South Brazil, Kenya, and the U.S.A. contained the organism. There is a pronounced vegetation effect. Panicum maximum seems the most favorable among the forage grasses, while few positive samples were found under virgin tropical forest. Legume roots contained less S. lipoferum than adjacent soils. More than 80% of the samples from cereal roots (maize, sorghum, wheat, and rye) grown in fields fertilized with PK and Mo, in Rio de Janeiro State, were positive. Maize and sorghum grown under similar conditions in Wisconsin contained less than 10% of positive samples, but when maize fields were inoculated 90% of the root samples contained S. lipoferum. Alluvial soils were more favorable than eroded hill soils. Occurrence in soil was strongly pH-dependent with a pH around 7, being optimal (correlation coefficient r = 0.90). Sporadic occurrence was observed even in soils with pH 4.8. Surface-sterilized P. maximum roots collected from soils with pH ranging from 4.8 to 7.2 contained high S. lipoferum numbers which did not correlate with soil pH (r = 0.41). Amendment with malate of acid soils was not very effective in increasing nitrogenase (N2-ase) activity, but in two soils with pH above 6.4, high N2-ase activity was obtained after 16 to 48 h of incubation. In two soils from a temperate climate region, inoculation with S. lipoferum increased N2-ase activity produced through malate amendment."}
{"id": "PMID:10063", "title": "Thermothrix thioparus gen. et sp. nov. a facultatively anaerobic facultative chemolithotroph living at neutral pH and high temperature.", "content": "Thermothrix thioparus gen. et ep. nov. occurs naturally in a New Mexico hot spring at a temperature of 74 degrees C, a pH of 7.0, and a HS- concentration of 1 mg/litre. The organism is gram-negative, non-motile, 0.5-1.0 X 3-20 mum, and forms cell chains up to 1 cm in length. The resulting filaments do not possess a sheath. Sulfur is deposited extracellularly. The organism was isolated using an autotrophic medium with HS- as the energy source and NO3- as the terminal electron acceptor. Anaerobically either NO2- or NO3- is required, NO2- is formed from NO3-, and no observable gas is evolved. Oxygen can also be used as the terminal electron acceptor, but growth is poor because of the decreased solubility of O2 at temperatures required for growth. Alternate energy sources used aerobically and anaerobically include hexose, HS-, SO3-, and S2O3=. The temperature optimum is 70-73 degrees C and growth occurs from 62 to 77 degrees C. The organism's thermal and physiological characteristics are compared to those of Bacillus stearothermophilus, Methanobacterium thermoautotrophicum, Sulfolobus acidocalderius, Thermus aquaticus, Thermus flavus, as well as Thiobacillus denitrificans, the latter being the only other facultatively anaerobic chemolithotroph which has been isolated and described.", "contents": "Thermothrix thioparus gen. et sp. nov. a facultatively anaerobic facultative chemolithotroph living at neutral pH and high temperature. Thermothrix thioparus gen. et ep. nov. occurs naturally in a New Mexico hot spring at a temperature of 74 degrees C, a pH of 7.0, and a HS- concentration of 1 mg/litre. The organism is gram-negative, non-motile, 0.5-1.0 X 3-20 mum, and forms cell chains up to 1 cm in length. The resulting filaments do not possess a sheath. Sulfur is deposited extracellularly. The organism was isolated using an autotrophic medium with HS- as the energy source and NO3- as the terminal electron acceptor. Anaerobically either NO2- or NO3- is required, NO2- is formed from NO3-, and no observable gas is evolved. Oxygen can also be used as the terminal electron acceptor, but growth is poor because of the decreased solubility of O2 at temperatures required for growth. Alternate energy sources used aerobically and anaerobically include hexose, HS-, SO3-, and S2O3=. The temperature optimum is 70-73 degrees C and growth occurs from 62 to 77 degrees C. The organism's thermal and physiological characteristics are compared to those of Bacillus stearothermophilus, Methanobacterium thermoautotrophicum, Sulfolobus acidocalderius, Thermus aquaticus, Thermus flavus, as well as Thiobacillus denitrificans, the latter being the only other facultatively anaerobic chemolithotroph which has been isolated and described."}
{"id": "PMID:10064", "title": "Comparison of talc-Celite and polyelectrolyte 60 in virus recovery from sewage: development of technique and experiments with poliovirus (type 1, Sabin)-contaminated multilitre samples.", "content": "For virus recovery from sewage, a mixture of talc and Celite was tested as a possible inexpensive substitute for polyelectrolyte 60 (PE 60). After adjustment of pH to 6 and the addition of 45-60 plaque forming units (PFU)/ml of poliovirus type I (Sabin) to the sewage sample under test, 100 ml of it was passed through either a PE 60 (400 mg) or a talc (300 mg)-Celite (100 mg) layer; the layer-adsorbed virus was eluted with 10 ml of 10% fetal calf serum (FCS) in saline (pH 7.2). In these experiments, PE 60 layers recovered 73-80% (mean 76%) of the input virus. In comparison, virus recoveries with the talc-Celite layers were 65-70% (mean 68%). Passage of 5 litres of raw sewage (containing 50 to 1.26 X 10(5) PFU/100 ml of the poliovirus) through the talc (15 g)-Celite (5 g) layers and virus elution with 50 ml of 10% FCS in saline gave virus recoveries of 33-63% (mean 49%). Except for pH adjustment and prefiltration through two layers of gauze to remove large solids, no other sample pretreatment was found to be necessary. Application of this technique to recovery of indigenous viruses from field samples of raw sewage and effluents has been highly satisfactory.", "contents": "Comparison of talc-Celite and polyelectrolyte 60 in virus recovery from sewage: development of technique and experiments with poliovirus (type 1, Sabin)-contaminated multilitre samples. For virus recovery from sewage, a mixture of talc and Celite was tested as a possible inexpensive substitute for polyelectrolyte 60 (PE 60). After adjustment of pH to 6 and the addition of 45-60 plaque forming units (PFU)/ml of poliovirus type I (Sabin) to the sewage sample under test, 100 ml of it was passed through either a PE 60 (400 mg) or a talc (300 mg)-Celite (100 mg) layer; the layer-adsorbed virus was eluted with 10 ml of 10% fetal calf serum (FCS) in saline (pH 7.2). In these experiments, PE 60 layers recovered 73-80% (mean 76%) of the input virus. In comparison, virus recoveries with the talc-Celite layers were 65-70% (mean 68%). Passage of 5 litres of raw sewage (containing 50 to 1.26 X 10(5) PFU/100 ml of the poliovirus) through the talc (15 g)-Celite (5 g) layers and virus elution with 50 ml of 10% FCS in saline gave virus recoveries of 33-63% (mean 49%). Except for pH adjustment and prefiltration through two layers of gauze to remove large solids, no other sample pretreatment was found to be necessary. Application of this technique to recovery of indigenous viruses from field samples of raw sewage and effluents has been highly satisfactory."}
{"id": "PMID:10065", "title": "The effects of pH and temperature on the assay of superoxide dismutase.", "content": "A simple and reliable method for the measurement of superoxide dismutase (EC 1.15.1.1) activity is described. The method is based on a linear inhibition of the reduction of acetylated cytochrome c by superoxide dismutase.", "contents": "The effects of pH and temperature on the assay of superoxide dismutase. A simple and reliable method for the measurement of superoxide dismutase (EC 1.15.1.1) activity is described. The method is based on a linear inhibition of the reduction of acetylated cytochrome c by superoxide dismutase."}
{"id": "PMID:10066", "title": "Biosynthesis of lysine in Saccharomyces cervisiae: properties and spectrophotometric determination of homocitrate synthase activity.", "content": "A rapid assay is described for homocitrate synthase (EC 4.1.3.21) of the lysine biosynthetic pathway of Saccharomyces cerevisiae. The alpha-ketoglutarate-dependent cleavage of acetyl-coA was measured spectrophotometrically as decrease in absorbance at 600 nm in the presence of 2,6-dichlorophenol-indophenol and enzyme from the wild type strain X2180. This activity was also present in citrate synthaseless glutamate auxotroph glu3, and the activity was inhibited by 5 mM L-lysine. Radioactive homocitric acid was obtained from a reaction mixture containing [1-14C]acetyl-coA. Homocitrate synthase activity was dependent upon time, both substrates, and enzyme. The activity exhibited a pH and temperature optimum of 7.5-8.0 and 32 degrees C, respectively, and was inhibited by metal-chelating and sulfhydryl-binding agents.", "contents": "Biosynthesis of lysine in Saccharomyces cervisiae: properties and spectrophotometric determination of homocitrate synthase activity. A rapid assay is described for homocitrate synthase (EC 4.1.3.21) of the lysine biosynthetic pathway of Saccharomyces cerevisiae. The alpha-ketoglutarate-dependent cleavage of acetyl-coA was measured spectrophotometrically as decrease in absorbance at 600 nm in the presence of 2,6-dichlorophenol-indophenol and enzyme from the wild type strain X2180. This activity was also present in citrate synthaseless glutamate auxotroph glu3, and the activity was inhibited by 5 mM L-lysine. Radioactive homocitric acid was obtained from a reaction mixture containing [1-14C]acetyl-coA. Homocitrate synthase activity was dependent upon time, both substrates, and enzyme. The activity exhibited a pH and temperature optimum of 7.5-8.0 and 32 degrees C, respectively, and was inhibited by metal-chelating and sulfhydryl-binding agents."}
{"id": "PMID:10067", "title": "Dependence of the superficial layers of Spirillum putridiconchylium on Ca2+ or Sr2+.", "content": "Chelating agents disrupted the superficial layers on Spirillum putridiconchylium and adsorption of cationized ferritin indicated that both upper and lower surfaces of superficial layer fragments, as well as the outer membrane surface, possessed areas which were negatively charged. Growth of the bacterium in 1% casamino acids (vitamin free) resulted in cells which were devoid of the superficial layers, and negative staining of these cells revealed in amorphous precipitate together with a vesicular outer membrane component extruding from their surfaces into the medium. Addition of either 1 mM Ca2+ or 1 mM Sr2+ to the growth medium produced the typical regularly structured cell surface, whereas addition of equal concentrations of Li+, Na+, K+, Mg2+, Ba2+, Mn2+, Fe3+, or three polyamines produced the structureless surface.", "contents": "Dependence of the superficial layers of Spirillum putridiconchylium on Ca2+ or Sr2+. Chelating agents disrupted the superficial layers on Spirillum putridiconchylium and adsorption of cationized ferritin indicated that both upper and lower surfaces of superficial layer fragments, as well as the outer membrane surface, possessed areas which were negatively charged. Growth of the bacterium in 1% casamino acids (vitamin free) resulted in cells which were devoid of the superficial layers, and negative staining of these cells revealed in amorphous precipitate together with a vesicular outer membrane component extruding from their surfaces into the medium. Addition of either 1 mM Ca2+ or 1 mM Sr2+ to the growth medium produced the typical regularly structured cell surface, whereas addition of equal concentrations of Li+, Na+, K+, Mg2+, Ba2+, Mn2+, Fe3+, or three polyamines produced the structureless surface."}
{"id": "PMID:10068", "title": "Some properties of p-coumarate decarboxylase from Cladosporium phlei.", "content": "The optimal pH and temperature of p-coumarate decarboxylase were 6.0 and 23 degrees C respectively. The enzyme activity was reduced to three quarters by heat treatment at 35 degrees C for 5 min and by half at 25 degrees C in 24 h, but kept almost unchanged at -20 degrees C at least for 10 days. The activity was not inhibited by potassium cyanide, sodium diethyldithiocarbamate, ethylenediaminetetraacetic acid disodium salt, or sodium citrate at 10 mM concentration, but was inhibited by p-chloromercuribenzoate or iodoacetate at 0.1 mM, the inhibition by the former being prevented to a great extent by the presence of reduced glutathione or dithiothreitol. The activity was inhibited by maleic acid cinnamic acid, or p-methoxycinnamic acid, but not by fumaric acid, acrylic acid, p-hydroxystyrene, furcatin p-hydroxyphenylacetic acid, or phloretic acid. An unsubstituted p-hydroxy group on the benzene ring and an acrylic acid side chain were required for the enzyme activity. Km value for trans-p-coumaric acid was about 6.5 X 10(-4) M.", "contents": "Some properties of p-coumarate decarboxylase from Cladosporium phlei. The optimal pH and temperature of p-coumarate decarboxylase were 6.0 and 23 degrees C respectively. The enzyme activity was reduced to three quarters by heat treatment at 35 degrees C for 5 min and by half at 25 degrees C in 24 h, but kept almost unchanged at -20 degrees C at least for 10 days. The activity was not inhibited by potassium cyanide, sodium diethyldithiocarbamate, ethylenediaminetetraacetic acid disodium salt, or sodium citrate at 10 mM concentration, but was inhibited by p-chloromercuribenzoate or iodoacetate at 0.1 mM, the inhibition by the former being prevented to a great extent by the presence of reduced glutathione or dithiothreitol. The activity was inhibited by maleic acid cinnamic acid, or p-methoxycinnamic acid, but not by fumaric acid, acrylic acid, p-hydroxystyrene, furcatin p-hydroxyphenylacetic acid, or phloretic acid. An unsubstituted p-hydroxy group on the benzene ring and an acrylic acid side chain were required for the enzyme activity. Km value for trans-p-coumaric acid was about 6.5 X 10(-4) M."}
{"id": "PMID:10069", "title": "Production of volatiles from decomposing plant tissues and effect of these volatiles on Rhizoctonia solani in culture.", "content": "Volatiles, of which NH3 is a major component, were evolved from decomposing immature corn tissue (c:n9) and affected R. solani in culture two ways: they supplied additional nitrogen to the growth medium so that fungal mycelial growth increased; and they raised substrate pH from 5.5 to 8.2 which induced melanization of mycelium. Volatiles increased fungus growth and pigmentation within 2 weeks of amendment addition to soil. Increases were concomitant with NH3 production from corn tissue. More NH3 evolved from decomposing corn tissues of C:N9 and 17 than from those of C-N 33 and 81. More growth and pigmentation occurred in flasks through which volatiles from decomposing corn (C:N9) were passed than in flasks through which volatiles from nonamended soil or decomposing corn (C:N81) were passed. Carbon dioxide from decomposing tissues did not affect growth or pigmentation. Twice as much NH3 evolved from corn tissue (C:N9) which decomposed in saturated soil than from tissue which decomposed in soil at 50% of its water-holding capacity. Pigment production doubled under saturated conditions.", "contents": "Production of volatiles from decomposing plant tissues and effect of these volatiles on Rhizoctonia solani in culture. Volatiles, of which NH3 is a major component, were evolved from decomposing immature corn tissue (c:n9) and affected R. solani in culture two ways: they supplied additional nitrogen to the growth medium so that fungal mycelial growth increased; and they raised substrate pH from 5.5 to 8.2 which induced melanization of mycelium. Volatiles increased fungus growth and pigmentation within 2 weeks of amendment addition to soil. Increases were concomitant with NH3 production from corn tissue. More NH3 evolved from decomposing corn tissues of C:N9 and 17 than from those of C-N 33 and 81. More growth and pigmentation occurred in flasks through which volatiles from decomposing corn (C:N9) were passed than in flasks through which volatiles from nonamended soil or decomposing corn (C:N81) were passed. Carbon dioxide from decomposing tissues did not affect growth or pigmentation. Twice as much NH3 evolved from corn tissue (C:N9) which decomposed in saturated soil than from tissue which decomposed in soil at 50% of its water-holding capacity. Pigment production doubled under saturated conditions."}
{"id": "PMID:10070", "title": "Factors affecting rate of methane formation from acetic acid by enriched methanogenic cultures.", "content": "A stable enrichment culture converting acetic acid to methane was successfully obtained from a pear waste digester, using a synthetic substrate solution with acetic acid as the main carbon source. This enrichment culture converted up to 10 mmol of acetic acid per litre per day at 35 degrees C and did not use hydrogen or formic acid in appreciable amounts as substrate for methane production instead of, or in addition to, acetic acid. The rate of conversion of acetic acid to methane was maximum at temperature of 40-45 degrees C, at a pH of 6.5 to 7.1, and was adversely affected by exposure to air, reducing agents, and high salt concentrations. The rate of conversion was independent of acetic acid concentration between 0.2 and 100 mM, but dropped markedly at concentrations below 0.2 mM.", "contents": "Factors affecting rate of methane formation from acetic acid by enriched methanogenic cultures. A stable enrichment culture converting acetic acid to methane was successfully obtained from a pear waste digester, using a synthetic substrate solution with acetic acid as the main carbon source. This enrichment culture converted up to 10 mmol of acetic acid per litre per day at 35 degrees C and did not use hydrogen or formic acid in appreciable amounts as substrate for methane production instead of, or in addition to, acetic acid. The rate of conversion of acetic acid to methane was maximum at temperature of 40-45 degrees C, at a pH of 6.5 to 7.1, and was adversely affected by exposure to air, reducing agents, and high salt concentrations. The rate of conversion was independent of acetic acid concentration between 0.2 and 100 mM, but dropped markedly at concentrations below 0.2 mM."}
{"id": "PMID:10071", "title": "Roles of low pH, carbon and inorganic nitrogen source use in chlamydospore formation by Fusarium solani.", "content": "Citrate and malate were poorer sources of exogenous carbon than several hexose, pentose, or disaccharide sugars for supporting macroconidial germination by Fusarium solani at high conidial density (1 X 10(5) condia/ml). Only citrate, however, failed to block chlamydospore morphogenesis to a degree comparable to glucose or other readily used sugars. Mostly immature chlamydospores were formed in the presence of citrate. At low conidial density (5 X 10(3) conidia/ml), exogenous carbon-independent macroconidial germination and subsequent rapid chalmydospore formation on germ tubes was not inhibited by ammonium or nitrate nitrogen. The citrate-phosphate buffered, low pH (4.0) medium of Cochrane induced more immature chlamydospore formation by F. solani than a pH 6.0 medium, but few mature chlamydospores were formed in either medium. Condensation of hyphal cytoplasm into developing chlamydospores, a character typical of chlamydospore formation, did not occur extensively and macroconidia, hyphae, and immature chlamydospores stained deeply with Sudan III, suggesting lipid biosynthesis. This inhibition of chlamydospore maturation may be due partly to nitrogen deficiency imposed by the high C:N ratio of the medium and to the presence of citrate. Only vesiculate hyphal cells were formed by F. solani f. sp. phaseoli in both media. Field soils to which the clone of F. solani used is indigenous had mean pH values ranging from 5.2 to 6.0.", "contents": "Roles of low pH, carbon and inorganic nitrogen source use in chlamydospore formation by Fusarium solani. Citrate and malate were poorer sources of exogenous carbon than several hexose, pentose, or disaccharide sugars for supporting macroconidial germination by Fusarium solani at high conidial density (1 X 10(5) condia/ml). Only citrate, however, failed to block chlamydospore morphogenesis to a degree comparable to glucose or other readily used sugars. Mostly immature chlamydospores were formed in the presence of citrate. At low conidial density (5 X 10(3) conidia/ml), exogenous carbon-independent macroconidial germination and subsequent rapid chalmydospore formation on germ tubes was not inhibited by ammonium or nitrate nitrogen. The citrate-phosphate buffered, low pH (4.0) medium of Cochrane induced more immature chlamydospore formation by F. solani than a pH 6.0 medium, but few mature chlamydospores were formed in either medium. Condensation of hyphal cytoplasm into developing chlamydospores, a character typical of chlamydospore formation, did not occur extensively and macroconidia, hyphae, and immature chlamydospores stained deeply with Sudan III, suggesting lipid biosynthesis. This inhibition of chlamydospore maturation may be due partly to nitrogen deficiency imposed by the high C:N ratio of the medium and to the presence of citrate. Only vesiculate hyphal cells were formed by F. solani f. sp. phaseoli in both media. Field soils to which the clone of F. solani used is indigenous had mean pH values ranging from 5.2 to 6.0."}
{"id": "PMID:10072", "title": "Transport of phenylalanine by conidia of Fusarium sulphureum.", "content": "L-Phenylalanine was actively transported by conidia of Fusarium sulphurenum Schlect (isolate 1). Uptake was optimal at pH 7, 30 degrees C; respiration-dependent; and was unaffected by relatively high internal concentrations of phenylalanine. The Km for transport was 1-3 X 10(-5) M and the Vmax was 2.5-4 nmol/min per milligram dry weight. Phenylalanine is transported by a general transport system for basic and neutral amino acids. Sucrose repressed uptake of phenylalanine and this repression was largely negated by cycloheximide. Efflux of accumulated phenylalanine was influx-dependent; this transport system deteriorated slowly with aging of the conidial culture.", "contents": "Transport of phenylalanine by conidia of Fusarium sulphureum. L-Phenylalanine was actively transported by conidia of Fusarium sulphurenum Schlect (isolate 1). Uptake was optimal at pH 7, 30 degrees C; respiration-dependent; and was unaffected by relatively high internal concentrations of phenylalanine. The Km for transport was 1-3 X 10(-5) M and the Vmax was 2.5-4 nmol/min per milligram dry weight. Phenylalanine is transported by a general transport system for basic and neutral amino acids. Sucrose repressed uptake of phenylalanine and this repression was largely negated by cycloheximide. Efflux of accumulated phenylalanine was influx-dependent; this transport system deteriorated slowly with aging of the conidial culture."}
{"id": "PMID:10074", "title": "Characterization of a strain of Methanospirillum hungatti.", "content": "The results of morphological, base ratio, nutritional, temperature, and pH studies on a strain of Methanospirillum hungatii, isolated from an anaerobic pear waste digester, are described. The isolate, designated as strain GP 1, was compared with some of the characteristics of type-strain M. hungatii JF 1. Strain GP 1 is Gram-negative, weakly motile, and a strict anaerobe with a guanine plus cytosine (G +C) content of 46.5 mol%. The preferred substrates for methane production are hydrogen, carbon dioxide, and formate. Acetate is used under certain conditions but its specific contribution to cell carbon and (or) methane formation was not established. The optimum temperature for both growth and methane production is 35 degrees C, but growth and methane production occur over the range 25-45 degrees C. Methane production is optimal at pH 7.0.", "contents": "Characterization of a strain of Methanospirillum hungatti. The results of morphological, base ratio, nutritional, temperature, and pH studies on a strain of Methanospirillum hungatii, isolated from an anaerobic pear waste digester, are described. The isolate, designated as strain GP 1, was compared with some of the characteristics of type-strain M. hungatii JF 1. Strain GP 1 is Gram-negative, weakly motile, and a strict anaerobe with a guanine plus cytosine (G +C) content of 46.5 mol%. The preferred substrates for methane production are hydrogen, carbon dioxide, and formate. Acetate is used under certain conditions but its specific contribution to cell carbon and (or) methane formation was not established. The optimum temperature for both growth and methane production is 35 degrees C, but growth and methane production occur over the range 25-45 degrees C. Methane production is optimal at pH 7.0."}
{"id": "PMID:10075", "title": "Psychotropic drug use among women.", "content": "The consistent 2:1 ratio of women to men in the receipt of prescriptions for psychotropic drugs is reflected in the higher rates for women of neurotic illness, symptoms of both physical and mental discomfort, and help-seeking and drug-taking behaviour. Physicians' perceptions of the problems presented by their male and female patients influence their prescribing of these drugs. Recent statistics in Ontario indicate that greater use of physicians' services by women is an inadequate explanation of the higher rate of prescribing of psychotropic drugs to women. A longitudinal study of a large insured population in Ontario showed that almost twice the proportion of females, compared with males, received a prescription for psychotropic drugs in 1970-71 and in 1973-74, a higher proportion of females received multiple prescriptions for each drug class, and males were more likely than females to have received only one prescription in a year.", "contents": "Psychotropic drug use among women. The consistent 2:1 ratio of women to men in the receipt of prescriptions for psychotropic drugs is reflected in the higher rates for women of neurotic illness, symptoms of both physical and mental discomfort, and help-seeking and drug-taking behaviour. Physicians' perceptions of the problems presented by their male and female patients influence their prescribing of these drugs. Recent statistics in Ontario indicate that greater use of physicians' services by women is an inadequate explanation of the higher rate of prescribing of psychotropic drugs to women. A longitudinal study of a large insured population in Ontario showed that almost twice the proportion of females, compared with males, received a prescription for psychotropic drugs in 1970-71 and in 1973-74, a higher proportion of females received multiple prescriptions for each drug class, and males were more likely than females to have received only one prescription in a year."}
{"id": "PMID:10076", "title": "Adoptive immunotherapy of a Gross virus producing lymphoma and a methylcholanthrene-induced fibrosarcoma in tolerant rats.", "content": "Immunological tolerance to Gross virus-specific transplantation antigens in rats given neonatae transfer of donor lymphoid cells beneath the kidney capsule of syngeneic recipient rats. Immune or normal donor cells invariably developed a cell-mediated immune reaction in kidneys of GV-tolerant recipients, presumably against GV antigens present on the surface of recipient lymphoid cells in the kidney. Spleen and lymph node cells from tolerant rats failed to develop a reaction in tolerant recipients, but developed a strong reaction to histoincompatible antigens in the kidneys of semisyngeneic tolerant rats. The immunologically tolerant state in the rats could be broken by adoptive transfer of spleen and lymph node cells from syngeneic rats immunized with GV-induced lymphoma cells. Immunotherapy of a GV-induced and also a GV-infected methylcholanthrene-induced fibrosarcoma growing in tolerant rats was successful when immune spleen and lymph node cells were administered i.p. 3 days after s.c. inoculation of 2 X 10(7) tumor cells in the case of the lymphoma, and 1 day after inoculation of 5 X 10(6) tumor cells in the case of the fibrosarcoma.", "contents": "Adoptive immunotherapy of a Gross virus producing lymphoma and a methylcholanthrene-induced fibrosarcoma in tolerant rats. Immunological tolerance to Gross virus-specific transplantation antigens in rats given neonatae transfer of donor lymphoid cells beneath the kidney capsule of syngeneic recipient rats. Immune or normal donor cells invariably developed a cell-mediated immune reaction in kidneys of GV-tolerant recipients, presumably against GV antigens present on the surface of recipient lymphoid cells in the kidney. Spleen and lymph node cells from tolerant rats failed to develop a reaction in tolerant recipients, but developed a strong reaction to histoincompatible antigens in the kidneys of semisyngeneic tolerant rats. The immunologically tolerant state in the rats could be broken by adoptive transfer of spleen and lymph node cells from syngeneic rats immunized with GV-induced lymphoma cells. Immunotherapy of a GV-induced and also a GV-infected methylcholanthrene-induced fibrosarcoma growing in tolerant rats was successful when immune spleen and lymph node cells were administered i.p. 3 days after s.c. inoculation of 2 X 10(7) tumor cells in the case of the lymphoma, and 1 day after inoculation of 5 X 10(6) tumor cells in the case of the fibrosarcoma."}
{"id": "PMID:10077", "title": "Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA.", "content": "The hepatic nuclear fraction isolated from 3-methylcholanthrene (MC)-treated rats contained enhanced levels of cytochrome P-450 and aryl hydrocarbon hydroxylase [benzo(a)pyrene (BP) monooxygenase], whereas the activities of epoxide hydrase and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase and the concentration of cytochrome b5 were not altered. The metabolite pattern of BP was investigated by using high-pressure liquid chromatography and was found to be similar in nuclei and microsomes from MC-treated rats. After incubation of the nuclear fraction with [3H]BP and reduced nicotinamide adenine dinculeotide phosphate, radioactivity was found to be associated with nuclear DNA and the extent of binding was markedly enhanced by pretreatment of the animals with MC. Binding was strongly inhibited by a-napthoflavone but was not influenced by 1,1,1-trichloropropene-2,3-oxide, an inhibitor of epoxide hydrase. In the presence of microsomes from MC-treated rats, increased binding of BP to DNA was observed in nuclei from both control and MC-treated rats; moreover, when the nuclear DNA was replaced by a corresponding amount of calf thymus DNA, the extent of binding was severalfold enhanced. In contrast to nuclei from control rats, the nuclear fraction from MC-treated rats showed an increase in bound radioactivity when incubated with a microsome-free supernatant, obtained by incubating microsomes from MC-treated rats with [3H]BP. The increase in extent of binding was eliminated in the presence of menadione or alpha-naphthoflavone. It is suggested that under the conditions used here the following different processes may have contributed to the total incorporation of BP products into nuclear DNA: (a) formation of DNA-binding products derived from BP by nuclear aryl hydrocarbon hydroxylase; (b) formation of DNA-binding products from microsomal BP metabolites by nuclear aryl hydrocarbon hydroxylase; and (c) direct transfer of reactive microsomal metabolites to nuclear DNA.", "contents": "Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA. The hepatic nuclear fraction isolated from 3-methylcholanthrene (MC)-treated rats contained enhanced levels of cytochrome P-450 and aryl hydrocarbon hydroxylase [benzo(a)pyrene (BP) monooxygenase], whereas the activities of epoxide hydrase and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase and the concentration of cytochrome b5 were not altered. The metabolite pattern of BP was investigated by using high-pressure liquid chromatography and was found to be similar in nuclei and microsomes from MC-treated rats. After incubation of the nuclear fraction with [3H]BP and reduced nicotinamide adenine dinculeotide phosphate, radioactivity was found to be associated with nuclear DNA and the extent of binding was markedly enhanced by pretreatment of the animals with MC. Binding was strongly inhibited by a-napthoflavone but was not influenced by 1,1,1-trichloropropene-2,3-oxide, an inhibitor of epoxide hydrase. In the presence of microsomes from MC-treated rats, increased binding of BP to DNA was observed in nuclei from both control and MC-treated rats; moreover, when the nuclear DNA was replaced by a corresponding amount of calf thymus DNA, the extent of binding was severalfold enhanced. In contrast to nuclei from control rats, the nuclear fraction from MC-treated rats showed an increase in bound radioactivity when incubated with a microsome-free supernatant, obtained by incubating microsomes from MC-treated rats with [3H]BP. The increase in extent of binding was eliminated in the presence of menadione or alpha-naphthoflavone. It is suggested that under the conditions used here the following different processes may have contributed to the total incorporation of BP products into nuclear DNA: (a) formation of DNA-binding products derived from BP by nuclear aryl hydrocarbon hydroxylase; (b) formation of DNA-binding products from microsomal BP metabolites by nuclear aryl hydrocarbon hydroxylase; and (c) direct transfer of reactive microsomal metabolites to nuclear DNA."}
{"id": "PMID:10078", "title": "Nonenzymatic reduction of benzo(a)pyrene diol-epoxides to trihydroxypentahydrobenzo(a)pyrenes by reduced nicotinamide adenine dinucleotide phosphate.", "content": "The diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene is a potent mutagen and possibly the ultimate carcinogenic form of benzo(a)pyrene. A (7/8,9)-trihydroxy-7,8,9,10,10-pentahydrobenzo(a)pyrene is formed from the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydroxybenzo(a)pyrene by reduction with reduced nicotinamide adenine dinucleotide phosphate. Its formation is linear with reduced nicotinamide adenine dinucleotide phosphate concentration and does not require the presence of enzyme. A (7,9/8)-trihydroxy-7,8,9,10,10-pentahydrobenzo(a)pyrene is similarly formed from the diol-epoxide r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene by reduction with reduced nicotinamide adenine dinucleotide phosphate. The structures of the trihydroxypentahydrobenzo(a)pyrenes were established by their ultraviolet absorption and mass spectra and their reaction with potassium triacetylosmate.", "contents": "Nonenzymatic reduction of benzo(a)pyrene diol-epoxides to trihydroxypentahydrobenzo(a)pyrenes by reduced nicotinamide adenine dinucleotide phosphate. The diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene is a potent mutagen and possibly the ultimate carcinogenic form of benzo(a)pyrene. A (7/8,9)-trihydroxy-7,8,9,10,10-pentahydrobenzo(a)pyrene is formed from the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydroxybenzo(a)pyrene by reduction with reduced nicotinamide adenine dinucleotide phosphate. Its formation is linear with reduced nicotinamide adenine dinucleotide phosphate concentration and does not require the presence of enzyme. A (7,9/8)-trihydroxy-7,8,9,10,10-pentahydrobenzo(a)pyrene is similarly formed from the diol-epoxide r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene by reduction with reduced nicotinamide adenine dinucleotide phosphate. The structures of the trihydroxypentahydrobenzo(a)pyrenes were established by their ultraviolet absorption and mass spectra and their reaction with potassium triacetylosmate."}
{"id": "PMID:10079", "title": "Establishment and characterization of human neuroblastoma cell lines.", "content": "Three new tissue culture cell lines, CHP-100, CHP-126, and CHP-134, have been established from explant cultures of human neuroblastoma. The cell lines have been characterized with respect to morphology, chromosomes constitution, growth, neural enzyme content, and their ability to grow in nude mice. The cells grow as dense masses comprised of fibroblast-or neuroblast-like cells with small processes. The cell lines differ in their neural enzyme acitivity. The chromosomal content of the 3 cell lines is near diploid, and all are capable of forming tumors in nude mice. The morphological findings indicate that the cells in culture resemble those found in the tumor, and the enzyme activities are consistent with those of nervous tissue. This the morphological, biochemical, and tumorigenic properties confirm that the 3 cell lines are neoplastic cells of neural origin.", "contents": "Establishment and characterization of human neuroblastoma cell lines. Three new tissue culture cell lines, CHP-100, CHP-126, and CHP-134, have been established from explant cultures of human neuroblastoma. The cell lines have been characterized with respect to morphology, chromosomes constitution, growth, neural enzyme content, and their ability to grow in nude mice. The cells grow as dense masses comprised of fibroblast-or neuroblast-like cells with small processes. The cell lines differ in their neural enzyme acitivity. The chromosomal content of the 3 cell lines is near diploid, and all are capable of forming tumors in nude mice. The morphological findings indicate that the cells in culture resemble those found in the tumor, and the enzyme activities are consistent with those of nervous tissue. This the morphological, biochemical, and tumorigenic properties confirm that the 3 cell lines are neoplastic cells of neural origin."}
{"id": "PMID:10080", "title": "Behavior of transaldolase (EC 2.2.1.2) and transketolase (EC 2.2.1.1) Activities in normal, neoplastic, differentiating, and regenerating liver.", "content": "The objective of this investigation was to throw light on the biological behavior  and metabolic regulation of hepatic enzymes of the nonoxidative branch of the pentose phosphate pathway. The activities of transaldolase (EC 2.2.1.2) and trasketolase (EC 2.2.1.1) Were compared in biological conditions that involve modulation of gene expression such as in starvation, in differentiation, after partial hepatectomy, and in a spectrum of hepatomas of different growth rates. The enzyme activities were determined under optimal kinetic conditions by spectrophotometric methods in the 100,000 X g supernatant fluids prepared from tissue homogenates. The kinetic properties of transaldolase and transketolase were similar in normal liver and in rapidly growing hepatoma 3924A. For transaldolase, apparent Km values of 0.13 mM (normal liver) and 0.17 mM (hepatoma) were observed for erythrose 4-phosphate and of 0.30 to 0.35 mM for fructose 6-phosphate. The pH optima in liver and hepatoma were at approximately 6.9 to 7.2. For the transketolase substrates, ribose 5-phosphate and xylulose 5-phosphate, the apparent Km values were 0.3 and 0.5 mM, respectively, in both liver and hepatoma. A broad pH optimum around 7.6 was observed in both tissues. In organ distribution studies, enzyme activities were measured in liver, intestinal mucosa, thymus, kidney, spleen, brain, adipose tissue, lung, heart, and skeletal muscle. Taking the specific activity of liver as 100%, transaldolase activity was the highest in intestinal mucosa (316%) and in thymus (219%); it was the lowest in heart (53%) and in skeletal muscle (21%). Transketolase activity was highest in kidney (155%) and lowest in heart (26%) and skeletal muscle (23%). Starvation decreased transaldolase and transketolase activities in 6 days to 69 and 74%, respectively, of those of the liver of the normal, fed rat. This was in the same range as the decrease in the protein concentration (66%y. In the liver tumors, transaldolase activity was increased 1.5- to 3.4-fold over the activities observed in normal control rat liver. Transketolase activity showed no relationship to tumor proliferation rate. In the regenerating liver at 24 hr after partial hepatectomy, the activity of both pentose phosphate pathway enzymes was in the same range as that of the sham-operated controls. In differentiation at the postnatal age of 5, 12, 23, and 32 days, hepatic transaldolase activities were 33, 44, 55, and 72%, respectively, of the activities observed in the 60-day-old, adult male rat. During the same period, transketolase activ-ties were 18, 21, 26, and 55% of the activities observed in liver of adult rat. The demonstration of increased transaldolase activity in hepatomas, irrespective of the degree of tumor malignancy, differentiation, or growth rate, suggests that the reprogramming of gene expression in malignant transformation is linked with an increase in the expression of this pentose phosphate pathway enzyme...", "contents": "Behavior of transaldolase (EC 2.2.1.2) and transketolase (EC 2.2.1.1) Activities in normal, neoplastic, differentiating, and regenerating liver. The objective of this investigation was to throw light on the biological behavior  and metabolic regulation of hepatic enzymes of the nonoxidative branch of the pentose phosphate pathway. The activities of transaldolase (EC 2.2.1.2) and trasketolase (EC 2.2.1.1) Were compared in biological conditions that involve modulation of gene expression such as in starvation, in differentiation, after partial hepatectomy, and in a spectrum of hepatomas of different growth rates. The enzyme activities were determined under optimal kinetic conditions by spectrophotometric methods in the 100,000 X g supernatant fluids prepared from tissue homogenates. The kinetic properties of transaldolase and transketolase were similar in normal liver and in rapidly growing hepatoma 3924A. For transaldolase, apparent Km values of 0.13 mM (normal liver) and 0.17 mM (hepatoma) were observed for erythrose 4-phosphate and of 0.30 to 0.35 mM for fructose 6-phosphate. The pH optima in liver and hepatoma were at approximately 6.9 to 7.2. For the transketolase substrates, ribose 5-phosphate and xylulose 5-phosphate, the apparent Km values were 0.3 and 0.5 mM, respectively, in both liver and hepatoma. A broad pH optimum around 7.6 was observed in both tissues. In organ distribution studies, enzyme activities were measured in liver, intestinal mucosa, thymus, kidney, spleen, brain, adipose tissue, lung, heart, and skeletal muscle. Taking the specific activity of liver as 100%, transaldolase activity was the highest in intestinal mucosa (316%) and in thymus (219%); it was the lowest in heart (53%) and in skeletal muscle (21%). Transketolase activity was highest in kidney (155%) and lowest in heart (26%) and skeletal muscle (23%). Starvation decreased transaldolase and transketolase activities in 6 days to 69 and 74%, respectively, of those of the liver of the normal, fed rat. This was in the same range as the decrease in the protein concentration (66%y. In the liver tumors, transaldolase activity was increased 1.5- to 3.4-fold over the activities observed in normal control rat liver. Transketolase activity showed no relationship to tumor proliferation rate. In the regenerating liver at 24 hr after partial hepatectomy, the activity of both pentose phosphate pathway enzymes was in the same range as that of the sham-operated controls. In differentiation at the postnatal age of 5, 12, 23, and 32 days, hepatic transaldolase activities were 33, 44, 55, and 72%, respectively, of the activities observed in the 60-day-old, adult male rat. During the same period, transketolase activ-ties were 18, 21, 26, and 55% of the activities observed in liver of adult rat. The demonstration of increased transaldolase activity in hepatomas, irrespective of the degree of tumor malignancy, differentiation, or growth rate, suggests that the reprogramming of gene expression in malignant transformation is linked with an increase in the expression of this pentose phosphate pathway enzyme..."}
{"id": "PMID:10081", "title": "L-Asparagine synthetase in serum as a marker for neoplasia.", "content": "L-Asparagine synthetase appears in serum approximately 7 days after the s.c. implantation of 1 X 10(5) cells of Leukemia 5178Y/AR (resistant to L-asparaginase) and increases in activity as the neoplasm grows and metastasizes. The principal source of the enzyme is the primary tumor. After intravranial inoculation of tumor, the rate of leakage of the enzyme is more pronounced than when the subcutaneous, intramuscular, or intraperitoneal routes are used. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037), a nitro-sourea effective in the palliation of L5178Y/AR, temporarily halts the influx of enzyme into the blood stream, as does surgical excision of the s.c. tumor nodules. Treatment of mice with L-asparaginase within 24 hr of inoculation of the tumor markedly augments both tumor growth and the rate of penetration of L-asparagine synthetase into the circulation. Several other L-asparagine synthetase into the circulation. Several other L-asparaginase-resistant tumors also were found to spill L-asparagine synthetase into the serum, but the correlation between this phenomenon and the specific activity of the enzyme in homogenates of the tumor was imperfect.", "contents": "L-Asparagine synthetase in serum as a marker for neoplasia. L-Asparagine synthetase appears in serum approximately 7 days after the s.c. implantation of 1 X 10(5) cells of Leukemia 5178Y/AR (resistant to L-asparaginase) and increases in activity as the neoplasm grows and metastasizes. The principal source of the enzyme is the primary tumor. After intravranial inoculation of tumor, the rate of leakage of the enzyme is more pronounced than when the subcutaneous, intramuscular, or intraperitoneal routes are used. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037), a nitro-sourea effective in the palliation of L5178Y/AR, temporarily halts the influx of enzyme into the blood stream, as does surgical excision of the s.c. tumor nodules. Treatment of mice with L-asparaginase within 24 hr of inoculation of the tumor markedly augments both tumor growth and the rate of penetration of L-asparagine synthetase into the circulation. Several other L-asparagine synthetase into the circulation. Several other L-asparaginase-resistant tumors also were found to spill L-asparagine synthetase into the serum, but the correlation between this phenomenon and the specific activity of the enzyme in homogenates of the tumor was imperfect."}
{"id": "PMID:10082", "title": "The isolation of lectins on acid-treated agarose.", "content": "The ability of several D-galactose and N-acetyl-D-galactosamine-binding lectins to bind to Sepharose was investigated. Lectins from soybean, Wistaria floribunda, Bauhinia purpurea alba, and Sophora japonica could be isolated by affinity chromatography on acid-treated Sepharose 6B. These lectins would not bind to untreated Sepharose 2B, 4B, and 6B. The binding of B. purpurea alba and S. japonica was temperature-dependent. The S. japonica lectin would bind only at high pH. Ricinus communis toxin also showed a temperature-dependence of binding; acid-treated Sepharose 6B was a better affinity support for the toxin than was untreated Sepharose 4B Lectins from lima bean, Dolichos biflorus, and kidney-bean phytohemagglutinin did not bind to Sepharose under any of the conditions studied.", "contents": "The isolation of lectins on acid-treated agarose. The ability of several D-galactose and N-acetyl-D-galactosamine-binding lectins to bind to Sepharose was investigated. Lectins from soybean, Wistaria floribunda, Bauhinia purpurea alba, and Sophora japonica could be isolated by affinity chromatography on acid-treated Sepharose 6B. These lectins would not bind to untreated Sepharose 2B, 4B, and 6B. The binding of B. purpurea alba and S. japonica was temperature-dependent. The S. japonica lectin would bind only at high pH. Ricinus communis toxin also showed a temperature-dependence of binding; acid-treated Sepharose 6B was a better affinity support for the toxin than was untreated Sepharose 4B Lectins from lima bean, Dolichos biflorus, and kidney-bean phytohemagglutinin did not bind to Sepharose under any of the conditions studied."}
{"id": "PMID:10085", "title": "Identification of a ribonuclease P-like activity from human KB cells.", "content": "An endoribonuclease which cleaves tRNA precursor molecules has been partially purified from human KB tissue culture cells. This activity is found in cytoplasmic fractions but is not detectable in the nucleoplasm. tRNA precursor molecules from both E. coli and KB cells are cleaved by this novel activity to produce 5' phosphate-terminated oligonucleotides. E coli RNAase P and the KB cell nuclease both make a single endonucleolytic scission in E. coli tRNATyr precursor, thereby separating the 41 extra nucleotides on the 5' end of the precursor molecule from the 5' terminal sequence of the mature tRNATyr molecule. The cleavage products generated from other E. coli tRNA precursors by the KB cell activity are identical in size to those produced by RNAase P. The KB cell endoribonuclease requires Mg2+ and a monovalent cation (Na+, K+, or NH4+) for function. The enzymatic activity has a broad pH optimum, centered near pH 8.0, and the activity is inhibited by tRNA. Several KB cell RNAs with long half-lives in vivo, including 5S and bulk 4S RNA, are not cleaved by this nuclease. The KB cell endoribonuclease resembles E. coli RNAase P in its substrate specificity, pH optimum, ion requirements, and sensitivity to tRNA. These properties and the cytoplasmic localization of the novel endoribonuclease indicate its involvement in the biosynthesis of KB cell tRNA.", "contents": "Identification of a ribonuclease P-like activity from human KB cells. An endoribonuclease which cleaves tRNA precursor molecules has been partially purified from human KB tissue culture cells. This activity is found in cytoplasmic fractions but is not detectable in the nucleoplasm. tRNA precursor molecules from both E. coli and KB cells are cleaved by this novel activity to produce 5' phosphate-terminated oligonucleotides. E coli RNAase P and the KB cell nuclease both make a single endonucleolytic scission in E. coli tRNATyr precursor, thereby separating the 41 extra nucleotides on the 5' end of the precursor molecule from the 5' terminal sequence of the mature tRNATyr molecule. The cleavage products generated from other E. coli tRNA precursors by the KB cell activity are identical in size to those produced by RNAase P. The KB cell endoribonuclease requires Mg2+ and a monovalent cation (Na+, K+, or NH4+) for function. The enzymatic activity has a broad pH optimum, centered near pH 8.0, and the activity is inhibited by tRNA. Several KB cell RNAs with long half-lives in vivo, including 5S and bulk 4S RNA, are not cleaved by this nuclease. The KB cell endoribonuclease resembles E. coli RNAase P in its substrate specificity, pH optimum, ion requirements, and sensitivity to tRNA. These properties and the cytoplasmic localization of the novel endoribonuclease indicate its involvement in the biosynthesis of KB cell tRNA."}
{"id": "PMID:10090", "title": "Changes in extracellular potassium activity in response to decreased pH in rabbit atrial muscle.", "content": "The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean control level of 3.6 mM to a new steady state level of 3.9 mM after 1 hour. When the pH was further decreased to 6.1, extracellular K+ activity increased to a mean of 4.9 mM. Following the change in pH, the increase in extracellular K+ activity occurred over a period of 30-40 minutes at which time a stable value was reached and maintained for the next hour. On return to normal pH the extracellular K+ activity returned to control with a time constant of 20 minutes or less. Measurements of intracellular K+ activity over 1 hour showed a mean loss of 3 mM at pH 6.8 and a mean loss of 8 mM at pH 6.1. The loss was reversible within 20 minutes of return to control pH. The increase in extracellular K+ activity was accompanied by a decrease in resting membrane potential as well as decreases in maximum dv/dt and overshoot of the action potential. The action potential contour underwent complex changes consisting of decrease in the plateau and a prolongation of the time to full repolarization.", "contents": "Changes in extracellular potassium activity in response to decreased pH in rabbit atrial muscle. The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean control level of 3.6 mM to a new steady state level of 3.9 mM after 1 hour. When the pH was further decreased to 6.1, extracellular K+ activity increased to a mean of 4.9 mM. Following the change in pH, the increase in extracellular K+ activity occurred over a period of 30-40 minutes at which time a stable value was reached and maintained for the next hour. On return to normal pH the extracellular K+ activity returned to control with a time constant of 20 minutes or less. Measurements of intracellular K+ activity over 1 hour showed a mean loss of 3 mM at pH 6.8 and a mean loss of 8 mM at pH 6.1. The loss was reversible within 20 minutes of return to control pH. The increase in extracellular K+ activity was accompanied by a decrease in resting membrane potential as well as decreases in maximum dv/dt and overshoot of the action potential. The action potential contour underwent complex changes consisting of decrease in the plateau and a prolongation of the time to full repolarization."}
{"id": "PMID:10091", "title": "The use of gamma-glutamyl transpeptidase in differentiating liver from bone isoenzymes of alkaline phosphatase.", "content": "Sixty-one patients with elevated alkaline phosphatase activity due to liver or bone diseases were studied. An attempt was made to identify the origin of the increased alkaline phosphatase by chemical inhibition, by inactivation by heat and urea, and by electrophoretic separation. The results obtained from these procedures were correlated with the gamma-glutamyl transpeptidase activities performed on each patient. We concluded from this study that gamma-glutamyl transpeptidase determination, together with alkaline phosphatase electrophoretic separations, are useful laboratory procedures for accurately identifying the origin of elevated alkaline phosphatase activity.", "contents": "The use of gamma-glutamyl transpeptidase in differentiating liver from bone isoenzymes of alkaline phosphatase. Sixty-one patients with elevated alkaline phosphatase activity due to liver or bone diseases were studied. An attempt was made to identify the origin of the increased alkaline phosphatase by chemical inhibition, by inactivation by heat and urea, and by electrophoretic separation. The results obtained from these procedures were correlated with the gamma-glutamyl transpeptidase activities performed on each patient. We concluded from this study that gamma-glutamyl transpeptidase determination, together with alkaline phosphatase electrophoretic separations, are useful laboratory procedures for accurately identifying the origin of elevated alkaline phosphatase activity."}
{"id": "PMID:10092", "title": "Normal limits of urinary excretion of eleven enzymes.", "content": "Urinary excretion of lactate dehydrogenase, hydroxybutyrate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, arylsulphatase A, alpha-glucosidase, beta-galactosidase, trehalase, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and leucinearylamidase was studies in a carefully selected group of 100 healthy subjects, 50 women and 50 men. Enzyme activities were assayed in 3-h morning samples after gel filtration of the urine. Activities were related to  time volume, and to urinary creatinine concentration. Several transforming functions had to be applied to enzyme output data to obtain an approximation to gaussian frequency distribution. Men showed a significantly higher excretion of gamma-glutamyltransferase, alpha-glucosidase, trehalase, N-acetyl-beta-glucosaminidase,beta-glucuronidase, and leucine arylamidase activity than did women if enzyme activity was related to urinary time volume. Women  excreted more lactate dehydrogenase, hydroxybutyrate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, alpha-glucosidase, trehalase, and N-acetyl-beta-glucosaminidase activity than did men, if urinary creatinine was used as the basis of reference. Reference intervals were calculated as 2.5 and 97.5 percentiles for both sexes.", "contents": "Normal limits of urinary excretion of eleven enzymes. Urinary excretion of lactate dehydrogenase, hydroxybutyrate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, arylsulphatase A, alpha-glucosidase, beta-galactosidase, trehalase, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and leucinearylamidase was studies in a carefully selected group of 100 healthy subjects, 50 women and 50 men. Enzyme activities were assayed in 3-h morning samples after gel filtration of the urine. Activities were related to  time volume, and to urinary creatinine concentration. Several transforming functions had to be applied to enzyme output data to obtain an approximation to gaussian frequency distribution. Men showed a significantly higher excretion of gamma-glutamyltransferase, alpha-glucosidase, trehalase, N-acetyl-beta-glucosaminidase,beta-glucuronidase, and leucine arylamidase activity than did women if enzyme activity was related to urinary time volume. Women  excreted more lactate dehydrogenase, hydroxybutyrate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, alpha-glucosidase, trehalase, and N-acetyl-beta-glucosaminidase activity than did men, if urinary creatinine was used as the basis of reference. Reference intervals were calculated as 2.5 and 97.5 percentiles for both sexes."}
{"id": "PMID:10093", "title": "Isolation and identification of benzodiazepine drugs and their metabolites in urine by use of Amberlite XAD-2 resin and thin-layer chromatography.", "content": "We used the method described here to detect and identify seven benzodiazepine derivatives--diazepam, chlorodiazepoxide, nitrazepam, cloxazolam, oxazolam, oxazepam, and medazepam--and their metabolites in the urine of rabbits given the seven drugs orally. We column-chromatographed 25-ml samples of urine on Amberlite XAD-2. The drugs and their metabolites in the urine were adsorbed by the resin, irrespective of urinary pH, and upon successive elution with methanol and ethyl acetate/methanol/acetic acid (90/10/0.1 by vol) they could be separated and extracted from the normal components of urine with satisfactory analytical recovery. The conjugated metabolites were then enzymatically hydrolyzed and the hydrolysate was extracted into ethyl acetate and the extract thin-layer chromatographed to detect and identify each drug and each of its metabolites. In an experiment in which the urine of human subjects given 5 mg of nitrazepam orally was analyzed by this method, the metabolites of nitrazepam in the 24-h urine could be identified satisfactorily.", "contents": "Isolation and identification of benzodiazepine drugs and their metabolites in urine by use of Amberlite XAD-2 resin and thin-layer chromatography. We used the method described here to detect and identify seven benzodiazepine derivatives--diazepam, chlorodiazepoxide, nitrazepam, cloxazolam, oxazolam, oxazepam, and medazepam--and their metabolites in the urine of rabbits given the seven drugs orally. We column-chromatographed 25-ml samples of urine on Amberlite XAD-2. The drugs and their metabolites in the urine were adsorbed by the resin, irrespective of urinary pH, and upon successive elution with methanol and ethyl acetate/methanol/acetic acid (90/10/0.1 by vol) they could be separated and extracted from the normal components of urine with satisfactory analytical recovery. The conjugated metabolites were then enzymatically hydrolyzed and the hydrolysate was extracted into ethyl acetate and the extract thin-layer chromatographed to detect and identify each drug and each of its metabolites. In an experiment in which the urine of human subjects given 5 mg of nitrazepam orally was analyzed by this method, the metabolites of nitrazepam in the 24-h urine could be identified satisfactorily."}
{"id": "PMID:10094", "title": "Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects.", "content": "Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin.", "contents": "Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects. Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin."}
{"id": "PMID:10095", "title": "Reaction of alkaline sodium picrate with creatinine: I. Kinetics and mechanism of formation of the mono-creatinine picric acid complex.", "content": "Spectrophotometric, kinetic, and nuclear magnetic resonance studies indicate that alkaline sodium picrate and creatinine react to form a 1/1 aduct between picric and creatinine, with a stability constant of log K= 4.26. Kinetic studies indicate that the forward reaction is first order with respect to picric acid, hydroxide, and creatinine concentration. The reverse reaction, the dissociation of the 1/1 complex, shows a complex dependence on hydroxide concentration. The expression for the observed pseudo-first-order rate constant in the presence of excess picric acid is: Kobsd = K1K0[P][OH] +[K2[OH]x. A value of K1K0 = 5.0 (mol/liter)-2s-1 is obtained. For accurate analytical results with this reaction, hydroxide concentration must be maintained at a constant value for both samples and standards.", "contents": "Reaction of alkaline sodium picrate with creatinine: I. Kinetics and mechanism of formation of the mono-creatinine picric acid complex. Spectrophotometric, kinetic, and nuclear magnetic resonance studies indicate that alkaline sodium picrate and creatinine react to form a 1/1 aduct between picric and creatinine, with a stability constant of log K= 4.26. Kinetic studies indicate that the forward reaction is first order with respect to picric acid, hydroxide, and creatinine concentration. The reverse reaction, the dissociation of the 1/1 complex, shows a complex dependence on hydroxide concentration. The expression for the observed pseudo-first-order rate constant in the presence of excess picric acid is: Kobsd = K1K0[P][OH] +[K2[OH]x. A value of K1K0 = 5.0 (mol/liter)-2s-1 is obtained. For accurate analytical results with this reaction, hydroxide concentration must be maintained at a constant value for both samples and standards."}
{"id": "PMID:10098", "title": "Long-term reproducibility of a new pH/blood-gas quality-control system compared to two other procedures.", "content": "The long-term precision and stability of a new quality-control system for blood pH and gas measurements are compared to that of tonometered bicarbonate solutions and serum-based preparations. The new system, consisting of gas-equilibrated bicarbonate solutions in glass ampuls, is shown to be as stable as the serum-based preparation, and as reproducible as either of the other methods. The new system, offering three discrete sets of control values, has certain advantages in the simultaneous quality of pH, carbon dioxide tension, and oxygen tension measurements.", "contents": "Long-term reproducibility of a new pH/blood-gas quality-control system compared to two other procedures. The long-term precision and stability of a new quality-control system for blood pH and gas measurements are compared to that of tonometered bicarbonate solutions and serum-based preparations. The new system, consisting of gas-equilibrated bicarbonate solutions in glass ampuls, is shown to be as stable as the serum-based preparation, and as reproducible as either of the other methods. The new system, offering three discrete sets of control values, has certain advantages in the simultaneous quality of pH, carbon dioxide tension, and oxygen tension measurements."}
{"id": "PMID:10099", "title": "Application of a vidicon spectrometer for simultaneous multicomponent drug determinations.", "content": "A rapid scanning vidicon spectrometer has been evaluated for the simultaneous determination of drugs in mixtures, without a separation step. Spectral data in the ultraviolet region are collected on-line with a small computer at repetition rates of 100 scans per second. Absorbance data at several wavelengths are processed by matrix equations to resolve them into the concentration of each component in each mixture. Results are reported for two-component mixtures of procainamide and N-acetylprocainamide in serum, for two-component aqueous mixtures of butabarbital and seconbarbital, and for seven-component aqueous mixtures of phenobarbital, diphenylhydantoin, aminophylline, acetaminophen, salicylamide, phenylbutazone, and secobarbital. We conclude that the computer-inter-faced vidicon spectrometer is a viable tool for simultaneous multicomponent determinations.", "contents": "Application of a vidicon spectrometer for simultaneous multicomponent drug determinations. A rapid scanning vidicon spectrometer has been evaluated for the simultaneous determination of drugs in mixtures, without a separation step. Spectral data in the ultraviolet region are collected on-line with a small computer at repetition rates of 100 scans per second. Absorbance data at several wavelengths are processed by matrix equations to resolve them into the concentration of each component in each mixture. Results are reported for two-component mixtures of procainamide and N-acetylprocainamide in serum, for two-component aqueous mixtures of butabarbital and seconbarbital, and for seven-component aqueous mixtures of phenobarbital, diphenylhydantoin, aminophylline, acetaminophen, salicylamide, phenylbutazone, and secobarbital. We conclude that the computer-inter-faced vidicon spectrometer is a viable tool for simultaneous multicomponent determinations."}
{"id": "PMID:10100", "title": "A search for the best buffer to use in assaying human lactate dehydrogenase with the lactate-to-pyruvate reaction.", "content": "Highly purified human lactate dehydrogenases I and V were assayed in 17 different buffers, at a variety of reaction pH's. Diethanolamine and 2-amino-2-methyl-1,3-propanediol provided the best measurements of the enzyme, assayed lactate-to-pyruvate. However, the commercial preparation of 2-amino-2-methyl-1,3-propanediol contained insoluble matter and was relatively expensive. All of the four buffers nowmost commonly used were found to present difficulties. Glycine and pyrophosphate were inhibotory tolactate dehydrogenase activity with increasing buffer concentration. 2-Amino-2-methyl-1-propanol had three major disadvantages: it is chemically unstable during reagent preparation; activity is dependent on buffer concentration; and the pH optima for isoenzymes I and V are vastly different. The pKa of tris(hydroxymethyl)aminomethane is 8.0 at 30 degrees C, whereas to measure total activity the reaction pH should be greater than 8.5; thus tris(hydroxymethyl)aminomethane has limited buffering capacity at the reaction pH.", "contents": "A search for the best buffer to use in assaying human lactate dehydrogenase with the lactate-to-pyruvate reaction. Highly purified human lactate dehydrogenases I and V were assayed in 17 different buffers, at a variety of reaction pH's. Diethanolamine and 2-amino-2-methyl-1,3-propanediol provided the best measurements of the enzyme, assayed lactate-to-pyruvate. However, the commercial preparation of 2-amino-2-methyl-1,3-propanediol contained insoluble matter and was relatively expensive. All of the four buffers nowmost commonly used were found to present difficulties. Glycine and pyrophosphate were inhibotory tolactate dehydrogenase activity with increasing buffer concentration. 2-Amino-2-methyl-1-propanol had three major disadvantages: it is chemically unstable during reagent preparation; activity is dependent on buffer concentration; and the pH optima for isoenzymes I and V are vastly different. The pKa of tris(hydroxymethyl)aminomethane is 8.0 at 30 degrees C, whereas to measure total activity the reaction pH should be greater than 8.5; thus tris(hydroxymethyl)aminomethane has limited buffering capacity at the reaction pH."}
{"id": "PMID:10101", "title": "Negative anion gap in a young adult with multiple myeloma.", "content": "A young patient with multiple myeloma was found to have a negative anion gap, with marked asymptomatic hyponatremia. The cause for his negative anion gap is thought to be the myeloma protein, which acts as a cation at physiological pH. Such a hyponatremia responds to reduction in serum concentration of paraprotein and should not be treated by sodium replacement.", "contents": "Negative anion gap in a young adult with multiple myeloma. A young patient with multiple myeloma was found to have a negative anion gap, with marked asymptomatic hyponatremia. The cause for his negative anion gap is thought to be the myeloma protein, which acts as a cation at physiological pH. Such a hyponatremia responds to reduction in serum concentration of paraprotein and should not be treated by sodium replacement."}
{"id": "PMID:10102", "title": "Characterization of adenosine deaminase isozymes from normal human erythrocytes.", "content": "Adenosine deaminase of phenotype ADA was partially purified by chromatography on CM-Sephadex C-50 and ammonium sulphate precipitation. With DEAE-Sephadex A-50 three isozymes could be detected. a. The KM values for the substrate adenosine were found to be 30 muM for each isozyme. b. pH optimum was 7.0 and the molecular weight estimated by gel filtration was found to be 30 000 for each isozyme. c. The heat stability of RBC-ADA type 1-1 was greater than type 1-2. The isozyme in type 2-1 representing the electrophoretic band of phenotype ADA2-2 is the most labile. d. ATP, ADP, AMP and cyclic AMP, PCMB and 6-methylmercaptopurine riboside were found to be competitive inhibitors with ADA in all three isozymes.", "contents": "Characterization of adenosine deaminase isozymes from normal human erythrocytes. Adenosine deaminase of phenotype ADA was partially purified by chromatography on CM-Sephadex C-50 and ammonium sulphate precipitation. With DEAE-Sephadex A-50 three isozymes could be detected. a. The KM values for the substrate adenosine were found to be 30 muM for each isozyme. b. pH optimum was 7.0 and the molecular weight estimated by gel filtration was found to be 30 000 for each isozyme. c. The heat stability of RBC-ADA type 1-1 was greater than type 1-2. The isozyme in type 2-1 representing the electrophoretic band of phenotype ADA2-2 is the most labile. d. ATP, ADP, AMP and cyclic AMP, PCMB and 6-methylmercaptopurine riboside were found to be competitive inhibitors with ADA in all three isozymes."}
{"id": "PMID:10103", "title": "An abnormal form of purine nucleoside phosphorylase in a family with a child with severe defective T-cell-and normal B-cell immunity.", "content": "1. Purine nucleoside phosphorylase and adenosine deaminase (ADA) were studied in normal red blood cells and lymphocytes and in the cells of a family with a child with a defective T-cell-and normal B-cell immunity. 2. In the propositus no purine nucleoside phosphorylase (NP) activity could be detected in her red cells and lymphocytes, while the ADA activity was somewhat increased. The NP activities of the father, mother and brother of the propositus are in the heterozygote range. The decreased activity of NP was not only found for the substrate inosine but also when guanosine or xanthosine were used as substrate. The mode of inheritance is autosomal recessive. 3. With starch gel electrophoresis no NP activity could be detected in the patient's haemolysate. The electrophoretic patterns of NP from the father, mother and brother of the patient seem to be the same as for normal NP with six bands of NP activity. 4. The nucleoside phosphorylases of the father, mother and brother of the patient were characterized by an increased KM for the substrate inosine, normal pH optimum and a decreased heat stability.", "contents": "An abnormal form of purine nucleoside phosphorylase in a family with a child with severe defective T-cell-and normal B-cell immunity. 1. Purine nucleoside phosphorylase and adenosine deaminase (ADA) were studied in normal red blood cells and lymphocytes and in the cells of a family with a child with a defective T-cell-and normal B-cell immunity. 2. In the propositus no purine nucleoside phosphorylase (NP) activity could be detected in her red cells and lymphocytes, while the ADA activity was somewhat increased. The NP activities of the father, mother and brother of the propositus are in the heterozygote range. The decreased activity of NP was not only found for the substrate inosine but also when guanosine or xanthosine were used as substrate. The mode of inheritance is autosomal recessive. 3. With starch gel electrophoresis no NP activity could be detected in the patient's haemolysate. The electrophoretic patterns of NP from the father, mother and brother of the patient seem to be the same as for normal NP with six bands of NP activity. 4. The nucleoside phosphorylases of the father, mother and brother of the patient were characterized by an increased KM for the substrate inosine, normal pH optimum and a decreased heat stability."}
{"id": "PMID:10104", "title": "[Sialyltransferase in human malignant melanoma].", "content": "A glycosyltransferase, CMP-N-acetylneuraminic acid : glycoprotein sialyltransferase was found in human malignant melanoma. Activities were measured with desialized glycoprotein as an exogenous acceptor. The enzyme was characterized by means of its pH optimum, 5.5, temperature optimum, 30 degrees C, KM values, 10 muM for the sugar nucleotide and 0.3 mM for desialized glycoprotein. It did not require exogenously added metal ions but was slightly stimulated by Mg2+. It required detergent for optimal activity. The effect of nucleotides and sugar nucleotides on enzyme activity has been investigated.", "contents": "[Sialyltransferase in human malignant melanoma]. A glycosyltransferase, CMP-N-acetylneuraminic acid : glycoprotein sialyltransferase was found in human malignant melanoma. Activities were measured with desialized glycoprotein as an exogenous acceptor. The enzyme was characterized by means of its pH optimum, 5.5, temperature optimum, 30 degrees C, KM values, 10 muM for the sugar nucleotide and 0.3 mM for desialized glycoprotein. It did not require exogenously added metal ions but was slightly stimulated by Mg2+. It required detergent for optimal activity. The effect of nucleotides and sugar nucleotides on enzyme activity has been investigated."}
{"id": "PMID:10105", "title": "Gamma-Glutamyl-3-carboxy-14-nitroanilide: the substrate of choice for routine determinations of gamma-glutamyl-transferase activity in serum?", "content": "Gamma-Glutamyl-3-carboxy-4-nitroanilide has been tested as donor substrate in the assay of gamma-glutamyltransferase activity in serum, glycylglycine being used as acceptor substrate. This donor substrate is highly solube even in neutral solutions, in contrast to the commonly used gamma-glutamyl-4-nitroanilide. The enzyme which apparently acts accordingly to a ping-pong bi bi kinetic mechanism, shows an absolute KM value for gamma-glutamyl-3-carboxy-4-nitroanilide of about 0.64 mmol/l, and for glycylglycine of about 13.4 mmol/l. The former KM value is significantly lower than that previously found for gamma-glutamyl-4-nitroanilide. The carboxyl derivative exhibits a marked competitive inhibitory effect on the gamma-glutamyltransferase. This effect is more pronounced than that of gamma-glutamyl-4-nitroanilide. The carboxyl derivative has somewhat higher absorbance in the range of wave length (400-420 nm) used to monitor the formation of the product. It is concluded that as donor substrate in the assay of gamma-glutamyltransferase activity of serum, the new derivative is not substantially superior to the gamma-glutamyl-4-nitroanilide conventionally used.", "contents": "Gamma-Glutamyl-3-carboxy-14-nitroanilide: the substrate of choice for routine determinations of gamma-glutamyl-transferase activity in serum? Gamma-Glutamyl-3-carboxy-4-nitroanilide has been tested as donor substrate in the assay of gamma-glutamyltransferase activity in serum, glycylglycine being used as acceptor substrate. This donor substrate is highly solube even in neutral solutions, in contrast to the commonly used gamma-glutamyl-4-nitroanilide. The enzyme which apparently acts accordingly to a ping-pong bi bi kinetic mechanism, shows an absolute KM value for gamma-glutamyl-3-carboxy-4-nitroanilide of about 0.64 mmol/l, and for glycylglycine of about 13.4 mmol/l. The former KM value is significantly lower than that previously found for gamma-glutamyl-4-nitroanilide. The carboxyl derivative exhibits a marked competitive inhibitory effect on the gamma-glutamyltransferase. This effect is more pronounced than that of gamma-glutamyl-4-nitroanilide. The carboxyl derivative has somewhat higher absorbance in the range of wave length (400-420 nm) used to monitor the formation of the product. It is concluded that as donor substrate in the assay of gamma-glutamyltransferase activity of serum, the new derivative is not substantially superior to the gamma-glutamyl-4-nitroanilide conventionally used."}
{"id": "PMID:10106", "title": "Serum gamma glutamyl transferase and alkaline phosphatase activities in epileptics receiving anticonvulsant therapy.", "content": "1. Serum gamma glutamyl transferase (gammaGT) and alkaline phosphatase (ALP) activities have been estimated in 49 epileptic patients taking anticonvulsant drugs. 2. Serum gammaGT activity was clearly elevated in 12 of the patients and borderline in 8, giving a 40% frequency of abnormal values. 3. Total serum ALP activity was elevated in 7 out of 33 adult patients and 2 of 16 juveniles. 4. Electrophoresis on polyacrylamide gel showed that the bone isoenzyme was responsible for most of the increased serum ALP activity and that even when the total was not elevated, the contribution of the bone isoenzyme was greater than normal. 5. There was no correlation between total serum ALP and gammaGT activities but elevations of serum gammaGT were often accompanied by an increase in the proportion of the bone enzyme in the total serum ALP activity.", "contents": "Serum gamma glutamyl transferase and alkaline phosphatase activities in epileptics receiving anticonvulsant therapy. 1. Serum gamma glutamyl transferase (gammaGT) and alkaline phosphatase (ALP) activities have been estimated in 49 epileptic patients taking anticonvulsant drugs. 2. Serum gammaGT activity was clearly elevated in 12 of the patients and borderline in 8, giving a 40% frequency of abnormal values. 3. Total serum ALP activity was elevated in 7 out of 33 adult patients and 2 of 16 juveniles. 4. Electrophoresis on polyacrylamide gel showed that the bone isoenzyme was responsible for most of the increased serum ALP activity and that even when the total was not elevated, the contribution of the bone isoenzyme was greater than normal. 5. There was no correlation between total serum ALP and gammaGT activities but elevations of serum gammaGT were often accompanied by an increase in the proportion of the bone enzyme in the total serum ALP activity."}
{"id": "PMID:10108", "title": "Determination of isoenzyme contents of lactic dehydrogenase activity and 2-hydroxybutyric dehydrogenase activity in lactic dehydrogenase preparations.", "content": "In this inestigation, a determination of the isoenzyme contents of LDH and HBD activities in lactate dehydrogenase preparations and the differences in the interaction of these preparations with NAD analogues were examined. The results obtained were as follows. 1. The activity ratio between oxidation and reduction in LDH reaction is shown to be similar in both H4 and M4 preparations, whereas for HBD activity, the ratio seems to be lower in the M4 preparation than in H4(H4/M = 1/2). 2. NAD and its analogues (NXD, TNAD, and TNXD) are shown to be useful coenzymes for the LDH reaction, while 3-acetyl derivatives appear to be unsuitable for this purpose because of their lower activity. HBD activity with 3-acetyl NXD is shown to be higher than with TNAD or TNXD. among these NAD analogues, 3-acetyl NXD gives the highest HBD activity, especially in the M4 preparation. 3. The LDH activity of H4 relative to M4 preparations has been shown to be maximal when 450 mM lactic acid with NAD or 15 mM lactic acid with TNXD are used. Under these conditions, the contents of LDH subunits can be estimated with considerable reliability. As to HBD activity, the content of LDH subunit having HBD activity has been estimated by determing the enzyme activity under conditions in which either 300 mM 2-hydroxybutyrate with 3-acetyl NXD or 15 mM 2-hydroxybutyrate with NAD are employed.", "contents": "Determination of isoenzyme contents of lactic dehydrogenase activity and 2-hydroxybutyric dehydrogenase activity in lactic dehydrogenase preparations. In this inestigation, a determination of the isoenzyme contents of LDH and HBD activities in lactate dehydrogenase preparations and the differences in the interaction of these preparations with NAD analogues were examined. The results obtained were as follows. 1. The activity ratio between oxidation and reduction in LDH reaction is shown to be similar in both H4 and M4 preparations, whereas for HBD activity, the ratio seems to be lower in the M4 preparation than in H4(H4/M = 1/2). 2. NAD and its analogues (NXD, TNAD, and TNXD) are shown to be useful coenzymes for the LDH reaction, while 3-acetyl derivatives appear to be unsuitable for this purpose because of their lower activity. HBD activity with 3-acetyl NXD is shown to be higher than with TNAD or TNXD. among these NAD analogues, 3-acetyl NXD gives the highest HBD activity, especially in the M4 preparation. 3. The LDH activity of H4 relative to M4 preparations has been shown to be maximal when 450 mM lactic acid with NAD or 15 mM lactic acid with TNXD are used. Under these conditions, the contents of LDH subunits can be estimated with considerable reliability. As to HBD activity, the content of LDH subunit having HBD activity has been estimated by determing the enzyme activity under conditions in which either 300 mM 2-hydroxybutyrate with 3-acetyl NXD or 15 mM 2-hydroxybutyrate with NAD are employed."}
{"id": "PMID:10109", "title": "beta-Glucuronidase and oestrogens in hydatidiform mole.", "content": "The activity of beta-glucuronidase (beta-D-glucuronide glycuronohydrolase, EC 3.2.1.31) in placental and hydatidiform mole tissue and in sera from non-pregnant, normal and molar pregnant women was determined. The oestrogen concentrations in the two solid tissues were also assayed. Significant differences were found in the activities of the enzyme between placental and molar tissues and among the various sera. The lower activity in molar serum corresponds to a lower concentration of oestrogens in molar tissues and may be regarded as a response to the alleviation of conjugation requirements.", "contents": "beta-Glucuronidase and oestrogens in hydatidiform mole. The activity of beta-glucuronidase (beta-D-glucuronide glycuronohydrolase, EC 3.2.1.31) in placental and hydatidiform mole tissue and in sera from non-pregnant, normal and molar pregnant women was determined. The oestrogen concentrations in the two solid tissues were also assayed. Significant differences were found in the activities of the enzyme between placental and molar tissues and among the various sera. The lower activity in molar serum corresponds to a lower concentration of oestrogens in molar tissues and may be regarded as a response to the alleviation of conjugation requirements."}
{"id": "PMID:10110", "title": "Serum gamma-glutamyl transpeptidase and physical exercise.", "content": "The immediate and delayed influence of exercise of variable type, duration and intensity on the serum gamma-glutamyl transpeptidase activity (gamma-GT) has been examined in athletes and untrained persons. The possible effects of exercise-induced changes in other parameters (plasma free glutamate, serum triglyceride, haemoconcentration) on the measured postexercise serum gamma-GT have been discussed, partly on the basis of our own experimental data. It appears that neither exercise itself, nor any one of the above mentioned factors (excepting a slight, transient effect of haemoconcentration after brief, intensive exertion) have noticeable influence on serum gamma-GT. Determinations of this enzyme for diagnostic purposes are therefore likely to be used without regard to acute and chronic exercise history in man.", "contents": "Serum gamma-glutamyl transpeptidase and physical exercise. The immediate and delayed influence of exercise of variable type, duration and intensity on the serum gamma-glutamyl transpeptidase activity (gamma-GT) has been examined in athletes and untrained persons. The possible effects of exercise-induced changes in other parameters (plasma free glutamate, serum triglyceride, haemoconcentration) on the measured postexercise serum gamma-GT have been discussed, partly on the basis of our own experimental data. It appears that neither exercise itself, nor any one of the above mentioned factors (excepting a slight, transient effect of haemoconcentration after brief, intensive exertion) have noticeable influence on serum gamma-GT. Determinations of this enzyme for diagnostic purposes are therefore likely to be used without regard to acute and chronic exercise history in man."}
{"id": "PMID:10112", "title": "A simple, rapid method for prenatal detection of defects in propionate metabolism.", "content": "Incorporation of radiolabel from propionate-1(-14)C into protein (TCA insoluble material) in fibroblasts or amniotic fluid cells, provides a rapid, simple means of detecting fetuses with inborn errors of propionate metabolism using small numbers of cells. Controls were easily differentiated from mutant lines over differing media pH conditions. This method was successfully used to diagnose correctly a normal fetus at risk for methylmalonic acidemia. This method can be used as an adjunct in diagnosis, but cannot replace direct enzyme analysis.", "contents": "A simple, rapid method for prenatal detection of defects in propionate metabolism. Incorporation of radiolabel from propionate-1(-14)C into protein (TCA insoluble material) in fibroblasts or amniotic fluid cells, provides a rapid, simple means of detecting fetuses with inborn errors of propionate metabolism using small numbers of cells. Controls were easily differentiated from mutant lines over differing media pH conditions. This method was successfully used to diagnose correctly a normal fetus at risk for methylmalonic acidemia. This method can be used as an adjunct in diagnosis, but cannot replace direct enzyme analysis."}
{"id": "PMID:10113", "title": "Effects of morphine on brain histamine, antinociception and activity in mice.", "content": "1. The effect of morphine on the histamine content of the mouse brain has been investigated. The changes in the brain histamine level have been related to morphine-induced analgesia and morphine-induced changes in locomotor activity. 2. With doses of morphine between 1 and 5 mg/kg there was a significant increase in histamine levels. The time required to produce a maximal rise in the brain histamine level with 5 mg/kg of morphine was 15 min. 3. There was a significant decrease in brain histamine levels with doses of morphine between 7-5 and 100 mg/kg. The time at which the greatest decrease was produced with 50 mg/kg was 30 min. 4. The time couse of the alteration of brain histamine by morphine did not correlate with its antinociceptive activity. Both the 5 and 50 mg/kg doses of morphine produced analgesia in mice whereas brain histamine levels were increased and decreased, respectively. 5. Pretreating mice with compounds which modify histaminergic function did not modify the antinociceptive action of morphine. 6. Morphine produced a biphasic effect on locomotor activity when the dose was increased from 0-5 through to 100 mg/kg. Doses up to 2-5 mg/kg caused a reduction of activity and doses above this produced significant increases. 7. There appears to be an inverse relationship between the morphine-induced changes of brain histamine and the morphine-induced changes in locomotor activity.", "contents": "Effects of morphine on brain histamine, antinociception and activity in mice. 1. The effect of morphine on the histamine content of the mouse brain has been investigated. The changes in the brain histamine level have been related to morphine-induced analgesia and morphine-induced changes in locomotor activity. 2. With doses of morphine between 1 and 5 mg/kg there was a significant increase in histamine levels. The time required to produce a maximal rise in the brain histamine level with 5 mg/kg of morphine was 15 min. 3. There was a significant decrease in brain histamine levels with doses of morphine between 7-5 and 100 mg/kg. The time at which the greatest decrease was produced with 50 mg/kg was 30 min. 4. The time couse of the alteration of brain histamine by morphine did not correlate with its antinociceptive activity. Both the 5 and 50 mg/kg doses of morphine produced analgesia in mice whereas brain histamine levels were increased and decreased, respectively. 5. Pretreating mice with compounds which modify histaminergic function did not modify the antinociceptive action of morphine. 6. Morphine produced a biphasic effect on locomotor activity when the dose was increased from 0-5 through to 100 mg/kg. Doses up to 2-5 mg/kg caused a reduction of activity and doses above this produced significant increases. 7. There appears to be an inverse relationship between the morphine-induced changes of brain histamine and the morphine-induced changes in locomotor activity."}
{"id": "PMID:10115", "title": "The influence of histamine on epithelial cell proliferation in the jejunum of the rat.", "content": "1. The influence of histamine and histamine receptor blockade on the mitotic rate in epithelial cell proliferation in epithelial cells lining the crypts of Lieberk\u00fchn in rat jejunum was studied. 2. Histamine injection resulted in an increase in the mitotic rate. This increase in mitotic rate was blocked by metiamide but not by mepyramine. 3. Prevention of histamine synthesis by alpha-methylhistidine administration did not alter the mitotic rate. 4. The mechanism by which histamine may influence crypt cell proliferation and possible role of cyclic GMP in this mediation are discussed.\u00bf", "contents": "The influence of histamine on epithelial cell proliferation in the jejunum of the rat. 1. The influence of histamine and histamine receptor blockade on the mitotic rate in epithelial cell proliferation in epithelial cells lining the crypts of Lieberk\u00fchn in rat jejunum was studied. 2. Histamine injection resulted in an increase in the mitotic rate. This increase in mitotic rate was blocked by metiamide but not by mepyramine. 3. Prevention of histamine synthesis by alpha-methylhistidine administration did not alter the mitotic rate. 4. The mechanism by which histamine may influence crypt cell proliferation and possible role of cyclic GMP in this mediation are discussed.\u00bf"}
{"id": "PMID:10116", "title": "Comparison of the bromureide sedative-hypnotic drugs, bromvaletone (bromisoval) and carbromal, and their chloro analogues in mice.", "content": "1. The central depressant effects of bromvaletone, carbromal and six non-bromo analogues were compared in mice. 2. The chloro analogues of bromvaletone and carbromal were slightly less potent as central depressant agents than the bromo compounds. 3. The chloro analogue of bromvaletone had the greatest margin between central depressant and lethal doses. 4. Lipophilicity (octanol-water partition coefficient) did not provide a unifying relationship for potency within this group of eight acylureas. However, within each of the two subsets of compounds, a linear relationship was found between relative potency and lipophilicity.", "contents": "Comparison of the bromureide sedative-hypnotic drugs, bromvaletone (bromisoval) and carbromal, and their chloro analogues in mice. 1. The central depressant effects of bromvaletone, carbromal and six non-bromo analogues were compared in mice. 2. The chloro analogues of bromvaletone and carbromal were slightly less potent as central depressant agents than the bromo compounds. 3. The chloro analogue of bromvaletone had the greatest margin between central depressant and lethal doses. 4. Lipophilicity (octanol-water partition coefficient) did not provide a unifying relationship for potency within this group of eight acylureas. However, within each of the two subsets of compounds, a linear relationship was found between relative potency and lipophilicity."}
{"id": "PMID:10117", "title": "Saturable metabolic pathways for ethotoin in man.", "content": "1. The urinary excretion pattern of ethotoin and five metabolites were examined in three patients receiving continuous treatment with ethotoin at two dose levels, in order to investigate the mechanism behind the dose-dependent kinetics of this anticonvulsant drug. 2. The results suggest a partial saturation in the dealkylation process at high dose levels in three patients. 3. A rough approximation of the Michaelis-Menten constants for different enzymatic processes was attempted. On the basis of the results obtained, the p-hydroxylation may be a saturable process. 4. The dose-dependent kinetics of ethotoin in man seem to be explicable by the existence of partly saturable enzymatic pathways.", "contents": "Saturable metabolic pathways for ethotoin in man. 1. The urinary excretion pattern of ethotoin and five metabolites were examined in three patients receiving continuous treatment with ethotoin at two dose levels, in order to investigate the mechanism behind the dose-dependent kinetics of this anticonvulsant drug. 2. The results suggest a partial saturation in the dealkylation process at high dose levels in three patients. 3. A rough approximation of the Michaelis-Menten constants for different enzymatic processes was attempted. On the basis of the results obtained, the p-hydroxylation may be a saturable process. 4. The dose-dependent kinetics of ethotoin in man seem to be explicable by the existence of partly saturable enzymatic pathways."}
{"id": "PMID:10114", "title": "Adrenergic factors influencing the mitotic rate in stratified squamous epithelium of the buccal mucosa of the rat.", "content": "1. An in vivo stathmokinetic technique was used to determine the immediate effect of various adrenoceptor agonists and antagonists on the mitotic rate in the stratified squamous epithelium of the rat buccal mucosa. 2. The mitotic rate increased significantly in rats treated with propranolol and with practolol, whereas the mitotic rate decreased significantly in rats treated with metaraminol. In animals treated with isoprenaline and phentolamine the mitotic rate did not differ significantly from the control value. 3. The nature of the involvement of adrenergic mechanisms with cell proliferation is still uncertain but both alpha- and beta-adrenergic mechanisms appear to be associated with the control of cell proliferation.", "contents": "Adrenergic factors influencing the mitotic rate in stratified squamous epithelium of the buccal mucosa of the rat. 1. An in vivo stathmokinetic technique was used to determine the immediate effect of various adrenoceptor agonists and antagonists on the mitotic rate in the stratified squamous epithelium of the rat buccal mucosa. 2. The mitotic rate increased significantly in rats treated with propranolol and with practolol, whereas the mitotic rate decreased significantly in rats treated with metaraminol. In animals treated with isoprenaline and phentolamine the mitotic rate did not differ significantly from the control value. 3. The nature of the involvement of adrenergic mechanisms with cell proliferation is still uncertain but both alpha- and beta-adrenergic mechanisms appear to be associated with the control of cell proliferation."}
{"id": "PMID:10121", "title": "Absorption and malabsorption of folates.", "content": "Folic acid is one of the 'younger' vitamins, yet it has attracted intensive study in the thirty years since the identification of pteroylglutamic acid and its polyglutamyl conjugates. The absorption and malabsorption of folates, natural, purified and synthetic, in disease has been studied more than any other vitamin and indeed folate absorption has become one clinical test of intestinal function. We know little about the release of folate from protein complexes, but we have learned, with the help of synthetic radiolabelled pteroylpolyglutamates that polyglutamyl folates are hydrolysed at or near the luminal border of the intestine and the released folate is efficiently absorbed. The rate limiting stage of folate absorption appears to be the transport of the monoglutamyl folate. In disease, and with drugs, folate malabsorption occurs primarily when monoglutamyl transport is depressed. The specific components of the folate transport system, listed in Table 4, are receiving increased attention. The mechanism of uptake is still a topic of controversy but a dual system including both a saturable and a diffusion component would explain most of the data. Reduction and methyl or formyl addition occur in the intestine but such metabolism is not obligatory for transport. The nature of folate binding within the cell and the function of specific folate binding proteins requires further study. At present we have little or no information about the mechanism of folate release from the epithelial cell to the circulation but this step also could influence the rate and specificity of overall process. The tools are now at hand to complete our understanding of the steps in folate absorption and metabolism. Such an understanding should facilitate the management of folate deficiency whenever it complicates gastrointestinal disease or drug therapy.", "contents": "Absorption and malabsorption of folates. Folic acid is one of the 'younger' vitamins, yet it has attracted intensive study in the thirty years since the identification of pteroylglutamic acid and its polyglutamyl conjugates. The absorption and malabsorption of folates, natural, purified and synthetic, in disease has been studied more than any other vitamin and indeed folate absorption has become one clinical test of intestinal function. We know little about the release of folate from protein complexes, but we have learned, with the help of synthetic radiolabelled pteroylpolyglutamates that polyglutamyl folates are hydrolysed at or near the luminal border of the intestine and the released folate is efficiently absorbed. The rate limiting stage of folate absorption appears to be the transport of the monoglutamyl folate. In disease, and with drugs, folate malabsorption occurs primarily when monoglutamyl transport is depressed. The specific components of the folate transport system, listed in Table 4, are receiving increased attention. The mechanism of uptake is still a topic of controversy but a dual system including both a saturable and a diffusion component would explain most of the data. Reduction and methyl or formyl addition occur in the intestine but such metabolism is not obligatory for transport. The nature of folate binding within the cell and the function of specific folate binding proteins requires further study. At present we have little or no information about the mechanism of folate release from the epithelial cell to the circulation but this step also could influence the rate and specificity of overall process. The tools are now at hand to complete our understanding of the steps in folate absorption and metabolism. Such an understanding should facilitate the management of folate deficiency whenever it complicates gastrointestinal disease or drug therapy."}
{"id": "PMID:10122", "title": "Vitamin B12--folate interrelations.", "content": "Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. Cytosine arabinoside, which also may cause megaloblastosis, may affect principally the synthesis of new DNA fragments. Since active protein synthesis is needed for the cell to enter the S phase and RNA synthesis is needed to prime new DNA synthesis, megaloblastic anaemia may be expected to occur only when DNA synthesis is inhibited but protein and RNA synthesis are relatively unimpaired...", "contents": "Vitamin B12--folate interrelations. Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. Cytosine arabinoside, which also may cause megaloblastosis, may affect principally the synthesis of new DNA fragments. Since active protein synthesis is needed for the cell to enter the S phase and RNA synthesis is needed to prime new DNA synthesis, megaloblastic anaemia may be expected to occur only when DNA synthesis is inhibited but protein and RNA synthesis are relatively unimpaired..."}
{"id": "PMID:10123", "title": "Effect of sulfasalazine on digoxin bioavailability.", "content": "Low levels of digoxin were noted in a patient receiving digoxin and sulfasalazine (SSA). Discontinuation of SSA resulted in a significant increase in serum digoxin levels. To determine whether or not SSA consistently interfered with the therapeutic effect of digoxin, both drugs were administered to 10 normal subjects in a crossover study. Each received 2 doses of digoxin (0.5 mg, elixir): one dose given alone, and a second dose after 6 days of treatment with SSA. When digoxin was given with SSA, the average area under the serum digoxin curve fell from the control value of 8.79 ng-hr-ml(-1) to 6.66 ng-hr-ml(-1) (p less than 0.05), fell and total urinary excretion decreased from 278 mcg/10 days to 228 mcg/10 days (p less than 0.025). These changes suggest interference with the bioavailability of digoxin by SSA. Studies were conducted to determine whether SSA inhibited digoxin absorption by physically absorbing the glycoside from solution. In vitro tests failed to reveal any significant adsorptive properties for SSA.", "contents": "Effect of sulfasalazine on digoxin bioavailability. Low levels of digoxin were noted in a patient receiving digoxin and sulfasalazine (SSA). Discontinuation of SSA resulted in a significant increase in serum digoxin levels. To determine whether or not SSA consistently interfered with the therapeutic effect of digoxin, both drugs were administered to 10 normal subjects in a crossover study. Each received 2 doses of digoxin (0.5 mg, elixir): one dose given alone, and a second dose after 6 days of treatment with SSA. When digoxin was given with SSA, the average area under the serum digoxin curve fell from the control value of 8.79 ng-hr-ml(-1) to 6.66 ng-hr-ml(-1) (p less than 0.05), fell and total urinary excretion decreased from 278 mcg/10 days to 228 mcg/10 days (p less than 0.025). These changes suggest interference with the bioavailability of digoxin by SSA. Studies were conducted to determine whether SSA inhibited digoxin absorption by physically absorbing the glycoside from solution. In vitro tests failed to reveal any significant adsorptive properties for SSA."}
{"id": "PMID:10118", "title": "The influence of beta-adrenoceptor antagonists on accommodation of the lens.", "content": "1. A study of the influence of single oral doses of the adrenergic-beta-receptor anatagonists alprenolol (100 mg) and propranolol (50 mg) on the accommodation of the lens was made in six healthy male subjects. 2. There was no significant influence of either drug on lens accommodation.", "contents": "The influence of beta-adrenoceptor antagonists on accommodation of the lens. 1. A study of the influence of single oral doses of the adrenergic-beta-receptor anatagonists alprenolol (100 mg) and propranolol (50 mg) on the accommodation of the lens was made in six healthy male subjects. 2. There was no significant influence of either drug on lens accommodation."}
{"id": "PMID:10124", "title": "Pharmacokinetics of oxprenolol in normal subjects.", "content": "The effect of oxprenolol administered intravenously (10 and 20 mg) and orally (20, 40, 80, and 160 mg) on plasma concentrations of the drug, resting heart rate, exercise-induced tachycardia, and arterial blood pressure was assessed as a function of time in 6 healthy subjects. The pharmacokinetics of oxprenolol following intravenous administration are best described as 2-compartnent open model with dose-dependent parameters. The mean (+/-SD) plasma half-life for oral doses is 1.94 +/- 0.37 and for intravenous doses is 2.31 +/- 0.64 hr. After oral administration, peak plasma concentrations are reached within 30 to 90 min, and the area under the plasma concentration-time curve varies linearly with the dose. Comparison of oral and intravenous data reveals the variation in bioavailabilty of orally administered oxprenolol to range from 19% to 74%. Unlike propranolol, oxprenolol does not show a saturable \"first-pass\" elimination effect. Blockade of beta-receptors occurs at plasma levels in excess of 60 ng/ml as evidenced by significant reductions in resting heart rate and exercise-induced tachycardia. Higher plasma concentrations of oxprenolol are required to lower blood pressure compared to those necessary to slow heart rate. These data suggest significant pharmacokinetic differences between oxprenolol and other beta-adrenergic receptor antagonists.", "contents": "Pharmacokinetics of oxprenolol in normal subjects. The effect of oxprenolol administered intravenously (10 and 20 mg) and orally (20, 40, 80, and 160 mg) on plasma concentrations of the drug, resting heart rate, exercise-induced tachycardia, and arterial blood pressure was assessed as a function of time in 6 healthy subjects. The pharmacokinetics of oxprenolol following intravenous administration are best described as 2-compartnent open model with dose-dependent parameters. The mean (+/-SD) plasma half-life for oral doses is 1.94 +/- 0.37 and for intravenous doses is 2.31 +/- 0.64 hr. After oral administration, peak plasma concentrations are reached within 30 to 90 min, and the area under the plasma concentration-time curve varies linearly with the dose. Comparison of oral and intravenous data reveals the variation in bioavailabilty of orally administered oxprenolol to range from 19% to 74%. Unlike propranolol, oxprenolol does not show a saturable \"first-pass\" elimination effect. Blockade of beta-receptors occurs at plasma levels in excess of 60 ng/ml as evidenced by significant reductions in resting heart rate and exercise-induced tachycardia. Higher plasma concentrations of oxprenolol are required to lower blood pressure compared to those necessary to slow heart rate. These data suggest significant pharmacokinetic differences between oxprenolol and other beta-adrenergic receptor antagonists."}
{"id": "PMID:10125", "title": "Clinical pharmacologic observations on atenolol, a beta-adrenoceptor blocker.", "content": "The effects of oral and intravenous administration of atenolol were studied in healthy volunteers. The oral administration of a series of single doses of atenolol reduced an exercise tachycardia. After a 200-mg dose, the effect on an exercise tachycardia was maximal at 3 hr and declined linearly with time at a rate of approximately 10% per 24 hr. The peak plasma atenolol concentration occurred at 3 hr and thereafter declined exponentially with time with an elimination half-life of 6.36 +/- 0.55 hr: 43 +/- 3.9% of the dose was excreted in the urine within 72 hr. There was a correlation between the reduction in an exercise tachycardia and the logarithm of the corresponding plasma concentration. The intravenous administration of atenolol reduced exercise tachycardia with a significant correlation between effect and plasma concentration. After 50 mg intravenously, 100% of the dose was recovered from the urine, and the clearance was 97.3 ml/min. Comparison of AUC O leads to chi after oral and intravenous administration of 50 mg showed the bioavailability to be 63% after oral drug. Repeated oral administration of atenolol 200 mg daily either as a single dose or in divided 12 hourly doses for 8 days maintained reduction of an exercise tachycardia of at least 24% during the period of drug administration. The plasma elimination half-life, area under the plasma concentration-time curve, and peak plasma concentration after 200 mg atenolol were not changed by chronic dosing for 8 days.", "contents": "Clinical pharmacologic observations on atenolol, a beta-adrenoceptor blocker. The effects of oral and intravenous administration of atenolol were studied in healthy volunteers. The oral administration of a series of single doses of atenolol reduced an exercise tachycardia. After a 200-mg dose, the effect on an exercise tachycardia was maximal at 3 hr and declined linearly with time at a rate of approximately 10% per 24 hr. The peak plasma atenolol concentration occurred at 3 hr and thereafter declined exponentially with time with an elimination half-life of 6.36 +/- 0.55 hr: 43 +/- 3.9% of the dose was excreted in the urine within 72 hr. There was a correlation between the reduction in an exercise tachycardia and the logarithm of the corresponding plasma concentration. The intravenous administration of atenolol reduced exercise tachycardia with a significant correlation between effect and plasma concentration. After 50 mg intravenously, 100% of the dose was recovered from the urine, and the clearance was 97.3 ml/min. Comparison of AUC O leads to chi after oral and intravenous administration of 50 mg showed the bioavailability to be 63% after oral drug. Repeated oral administration of atenolol 200 mg daily either as a single dose or in divided 12 hourly doses for 8 days maintained reduction of an exercise tachycardia of at least 24% during the period of drug administration. The plasma elimination half-life, area under the plasma concentration-time curve, and peak plasma concentration after 200 mg atenolol were not changed by chronic dosing for 8 days."}
{"id": "PMID:10126", "title": "Psychiatric sequelae of phencyclidine abuse.", "content": "Phencyclidine use has been noted to produce a psychosis of several week's duration in a small fraction of users. Descriptions of the premorbid personalities of those who became psychotic resemble descriptions of LSD and marijuana users who experienced prolonged psychiatric difficulty. In addition, the psychosis produced can often be recognized as a \"hallucinogen\" psychosis. Certain features of the phencyclidine psychosis, namely the neurologic abnormalities, dose-related severity of symptoms, and regularity of the length of illness, are not noted with other psychedelic drugs, leading to the conclusion that PCP psychosis is a drug effect rather than a brief functional psychosis precipitated by the disintegrating PCP experience. However, the infrequent occurrence of psychosis in the (apparently) large exposed population still suggests that this is a combination of drug effect and vulnerable, pathologic personality.", "contents": "Psychiatric sequelae of phencyclidine abuse. Phencyclidine use has been noted to produce a psychosis of several week's duration in a small fraction of users. Descriptions of the premorbid personalities of those who became psychotic resemble descriptions of LSD and marijuana users who experienced prolonged psychiatric difficulty. In addition, the psychosis produced can often be recognized as a \"hallucinogen\" psychosis. Certain features of the phencyclidine psychosis, namely the neurologic abnormalities, dose-related severity of symptoms, and regularity of the length of illness, are not noted with other psychedelic drugs, leading to the conclusion that PCP psychosis is a drug effect rather than a brief functional psychosis precipitated by the disintegrating PCP experience. However, the infrequent occurrence of psychosis in the (apparently) large exposed population still suggests that this is a combination of drug effect and vulnerable, pathologic personality."}
{"id": "PMID:10134", "title": "Intrarenal arterial aneurysms.", "content": "Intraparenchymal renal aneurysms have been reported with increasing frequency; yet, to our knowledge, this subject has not been reviewed in radiologic literature. The spectrum of such aneurysms includes congenital aneurysms, those secondary to disease usually affecting the main renal arteries, those associated with renal masses, microaneurysms, and false or pseudo aneurysms. Seemingly unrelated conditions, such as atherosclerosis, bacterial endocarditis, and trauma, can all produce similar radiographic appearance of aneurysmal dilatation within the kidney, albeit through differing mechanisms. In addition, there are several etiologies for renal microaneurysms, even though this finding has been considered specific for polyarteritis in the past. Although there were a few guidelines for recognizing certain specific etiologies based solely on the angiographic appearance, it must be appreciated that many of these conditions may be indistinguishable. The possibility of hemorrhage from such intrarenal aneurysms, and the question of whether such lesions are responsible for renovascular hypertension are also discussed.", "contents": "Intrarenal arterial aneurysms. Intraparenchymal renal aneurysms have been reported with increasing frequency; yet, to our knowledge, this subject has not been reviewed in radiologic literature. The spectrum of such aneurysms includes congenital aneurysms, those secondary to disease usually affecting the main renal arteries, those associated with renal masses, microaneurysms, and false or pseudo aneurysms. Seemingly unrelated conditions, such as atherosclerosis, bacterial endocarditis, and trauma, can all produce similar radiographic appearance of aneurysmal dilatation within the kidney, albeit through differing mechanisms. In addition, there are several etiologies for renal microaneurysms, even though this finding has been considered specific for polyarteritis in the past. Although there were a few guidelines for recognizing certain specific etiologies based solely on the angiographic appearance, it must be appreciated that many of these conditions may be indistinguishable. The possibility of hemorrhage from such intrarenal aneurysms, and the question of whether such lesions are responsible for renovascular hypertension are also discussed."}
{"id": "PMID:10136", "title": "Relationship between pulmonary hemodynamics and arterial pH and carbon dioxide tension in critically ill patients.", "content": "To ascertain the clinical significance of derangements in arterial pH and arterial carbon dioxide tension (PaCO2) in modifying pulmonary arterial pressures and pulmonary vascular resistance in critically ill patients, the relationship between these two sets of variables was evaluated in 75 patients. No significant differences in pulmonary hemodynamic values were found among patients with acidemia, a normal pH, or alkalemia, even at extreme pH values; and there was no consistent relationship between PaCO2 and each of the pulmonary hemodynamic measurements. In patients who initially had a normal pH but subsequently developed acidemia or alkalemia, there was also no significant correlation between changes in pH and pulmonary hemodynamic values. We conclude that abnormalities of pulmonary hemodynamic values in seriously ill patients are usually due to factors other than acid-base derangements. Of practical importance is the observation that the predictability of the pulmonary arterial wedge pressure from the pulmonary arterial diastolic pressure is not invalidated by acid-base disturbances.", "contents": "Relationship between pulmonary hemodynamics and arterial pH and carbon dioxide tension in critically ill patients. To ascertain the clinical significance of derangements in arterial pH and arterial carbon dioxide tension (PaCO2) in modifying pulmonary arterial pressures and pulmonary vascular resistance in critically ill patients, the relationship between these two sets of variables was evaluated in 75 patients. No significant differences in pulmonary hemodynamic values were found among patients with acidemia, a normal pH, or alkalemia, even at extreme pH values; and there was no consistent relationship between PaCO2 and each of the pulmonary hemodynamic measurements. In patients who initially had a normal pH but subsequently developed acidemia or alkalemia, there was also no significant correlation between changes in pH and pulmonary hemodynamic values. We conclude that abnormalities of pulmonary hemodynamic values in seriously ill patients are usually due to factors other than acid-base derangements. Of practical importance is the observation that the predictability of the pulmonary arterial wedge pressure from the pulmonary arterial diastolic pressure is not invalidated by acid-base disturbances."}
{"id": "PMID:10139", "title": "Polyamines and drug oxidations.", "content": "The addition of spermine or of spermidine to rat liver assay systems produced marked changes in a number of microsomal drug oxidations. The hydroxylation of aniline and the N-demethylation of ethylmorphine were both enhanced with concentrations of 1-10 mM spermine or of spermidine. The results with putrescine on ethylmorphine metabolism were less dramatic, and no effect could be observed with putrescine in studies with other drug substrates. In contrast to the enhancing effects, inhibition was observed when spermine or spermidine was added to p-nitroanisole O-demethylation assay mixtures, and no effect was observed in assays for acetanilide hydroxylation. The inhibiting and enhancing effects of the polyamines can be observed in assays containing liver preparations from both male and female rats, and those from rats pretreated with phenobarbital or 3-methylcholanthrene. In all studies, the alterations were kinetically noncompetitive. The effects were shown to be independent of the NADPH-generating system and the cation requirements, and were not mediated through an interaction with NADPH-cytochrome c reductase. The possibility is considered that the enhancing and inhibiting effects may be related to the ability of these polycations to bind to microsomal membranes and cause alterations at different sites of substrate interaction.", "contents": "Polyamines and drug oxidations. The addition of spermine or of spermidine to rat liver assay systems produced marked changes in a number of microsomal drug oxidations. The hydroxylation of aniline and the N-demethylation of ethylmorphine were both enhanced with concentrations of 1-10 mM spermine or of spermidine. The results with putrescine on ethylmorphine metabolism were less dramatic, and no effect could be observed with putrescine in studies with other drug substrates. In contrast to the enhancing effects, inhibition was observed when spermine or spermidine was added to p-nitroanisole O-demethylation assay mixtures, and no effect was observed in assays for acetanilide hydroxylation. The inhibiting and enhancing effects of the polyamines can be observed in assays containing liver preparations from both male and female rats, and those from rats pretreated with phenobarbital or 3-methylcholanthrene. In all studies, the alterations were kinetically noncompetitive. The effects were shown to be independent of the NADPH-generating system and the cation requirements, and were not mediated through an interaction with NADPH-cytochrome c reductase. The possibility is considered that the enhancing and inhibiting effects may be related to the ability of these polycations to bind to microsomal membranes and cause alterations at different sites of substrate interaction."}
{"id": "PMID:10140", "title": "Drug biotransformation in microsomes from the fetal stumptailed macaque, Macaca arctoides: hepatic N-demethylation.", "content": "The kinetics of the N-demethylation of benzphetamine, ethylmorphine, meperidine, and methadone have been studied in microsomes isolated from livers of the fetal stumptailed macaque (Macaca arctoides) during the last third of gestation. The apparent KM for each substrate did not change during this time period. Values were similar to those from livers of adult African green monkeys. The Vmax for each substrate, when expressed per mg of microsomal protein, did not change during the last third of gestation. N-demethylase activity (Vmax) per g of liver increased during the last third of gestation, as did the content of microsomal protein, cytochrome P-450 concentration, and liver weight. The amount of cytochrome P-450 per g of liver was greater in whole homogenates of the left physiological lobe than in those of the right physiological lobe of fetal liver obtained near term; no differences occurred in whole homogenates of the separate lobes of adult liver. This observation suggests that a differential capacity for drug (and possibly steroid) metabolism may exist between the two physiological lobes of fetal liver.", "contents": "Drug biotransformation in microsomes from the fetal stumptailed macaque, Macaca arctoides: hepatic N-demethylation. The kinetics of the N-demethylation of benzphetamine, ethylmorphine, meperidine, and methadone have been studied in microsomes isolated from livers of the fetal stumptailed macaque (Macaca arctoides) during the last third of gestation. The apparent KM for each substrate did not change during this time period. Values were similar to those from livers of adult African green monkeys. The Vmax for each substrate, when expressed per mg of microsomal protein, did not change during the last third of gestation. N-demethylase activity (Vmax) per g of liver increased during the last third of gestation, as did the content of microsomal protein, cytochrome P-450 concentration, and liver weight. The amount of cytochrome P-450 per g of liver was greater in whole homogenates of the left physiological lobe than in those of the right physiological lobe of fetal liver obtained near term; no differences occurred in whole homogenates of the separate lobes of adult liver. This observation suggests that a differential capacity for drug (and possibly steroid) metabolism may exist between the two physiological lobes of fetal liver."}
{"id": "PMID:10141", "title": "N-Hydroxylation of phenacetin by hamster liver microsomes.", "content": "Hamster liver microsomes have been shown to catalyze the N-hydroxylation of phenacetin. The reaction, which requires oxygen and NADPH, is inhibited by a carbon monoxide/oxygen atmosphere, indicating that it is catalyzed by a cytochrome P-450-dependent mixed-function oxidase. The N-hydroxyphenacetin can be further metabolized by the microsomes, and the reaction is inhibited by phenacetin.", "contents": "N-Hydroxylation of phenacetin by hamster liver microsomes. Hamster liver microsomes have been shown to catalyze the N-hydroxylation of phenacetin. The reaction, which requires oxygen and NADPH, is inhibited by a carbon monoxide/oxygen atmosphere, indicating that it is catalyzed by a cytochrome P-450-dependent mixed-function oxidase. The N-hydroxyphenacetin can be further metabolized by the microsomes, and the reaction is inhibited by phenacetin."}
{"id": "PMID:10142", "title": "Properties of microsomal enzyme systems that reduce N-hydroxyphentermine.", "content": "The reduction of N-hydroxyphentermine was studied in liver microsomes isolated from rat, guinea pig, and rabbit. The reduction requires a NADPH-generating system and was inhibited by oxygen and carbon monoxide. In the rat, the reduction was increased by phenobarbital pretreatment. Kinetic analysis of the reductase activity in rat liver microsomes suggests that the reduction of the hydroxylamine is mediated by at least two enzyme systems, one of which is a CO-sensitive system inducible by phenobarbital.", "contents": "Properties of microsomal enzyme systems that reduce N-hydroxyphentermine. The reduction of N-hydroxyphentermine was studied in liver microsomes isolated from rat, guinea pig, and rabbit. The reduction requires a NADPH-generating system and was inhibited by oxygen and carbon monoxide. In the rat, the reduction was increased by phenobarbital pretreatment. Kinetic analysis of the reductase activity in rat liver microsomes suggests that the reduction of the hydroxylamine is mediated by at least two enzyme systems, one of which is a CO-sensitive system inducible by phenobarbital."}
{"id": "PMID:10143", "title": "Cytochrome P-450 content and mixed-function oxidase activity in microsomes isolated from mouse skin.", "content": "A microsomal fraction, prepared from mouse skin, catalyzed the hydroxylation of benzpyrene and aniline and the deethylation of 7-ethoxycoumarin. Contamination of the preparation by cytochrome oxidase and cytochrome P-420 was determined by spectral analysis. The enzyme activities studied in mouse skin (Swiss-Webster CD-1) did not respond to topical application of 3-MC. Twenty-four hours after topical application of TCDD to mice, microsomes from skin had 50% greater benzpyrene hydroxylase and 7-ethoxycoumarin deethylase activity, and 4- to 8-fold greater activity of these enzymes was seen after 72 hr. Increases in cytochrome P-450 content of skin microsomes could be demonstrated 24 and 72 hr after topical TCDD treatment of mice. Cholate treatment (solubilization) of skin microsomes, followed by centrifugation, removed the contaminating cytochrome oxidase. Quantitative and qualitative analyses of cytochrome P-450 difference spectra were made from the solubilized preparations.", "contents": "Cytochrome P-450 content and mixed-function oxidase activity in microsomes isolated from mouse skin. A microsomal fraction, prepared from mouse skin, catalyzed the hydroxylation of benzpyrene and aniline and the deethylation of 7-ethoxycoumarin. Contamination of the preparation by cytochrome oxidase and cytochrome P-420 was determined by spectral analysis. The enzyme activities studied in mouse skin (Swiss-Webster CD-1) did not respond to topical application of 3-MC. Twenty-four hours after topical application of TCDD to mice, microsomes from skin had 50% greater benzpyrene hydroxylase and 7-ethoxycoumarin deethylase activity, and 4- to 8-fold greater activity of these enzymes was seen after 72 hr. Increases in cytochrome P-450 content of skin microsomes could be demonstrated 24 and 72 hr after topical TCDD treatment of mice. Cholate treatment (solubilization) of skin microsomes, followed by centrifugation, removed the contaminating cytochrome oxidase. Quantitative and qualitative analyses of cytochrome P-450 difference spectra were made from the solubilized preparations."}
{"id": "PMID:10144", "title": "Preservation of various microsomal drug metabolizing components in tissue preparations from the livers, lungs, and small intestines of rodents.", "content": "The livers, lungs, and small intestines of untreated rabbits and the livers of control rats were stored intact, or as microsomal suspensions, under liquid nitrogen at -196 degrees C. Aniline hydroxylase, aminopyrine demethylase, benzpyrene hydroxylase, biphenyl hydroxylase, NADPH-cytochrome c reductase, UDP-glucuronyltransferase activities, the microsomal content of cytochrome P-450, and the aniline- and benzphetamine-induced spectral changes were compared in fresh and stored preparations. Few significant changes in any of the above parameters resulted from storage of rabbit tissue preparations in liquid nitrogen for periods of up to 28 days. Pretreatment of rabbits with phenobarbital did not affect the stability of their stored microsomal preparations. Enzyme activities in the livers of untreated or 3-methylcholanthrene-pretreated rats were less stable to storage than in tissue preparations from rabbits stored under identical conditions. However, when rat hepatic microsomes were resuspended in KCl-HEPES supplemented with 1 mM EDTA before storage, enzyme activities were largely unaffected by freezing in liquid nitrogen.", "contents": "Preservation of various microsomal drug metabolizing components in tissue preparations from the livers, lungs, and small intestines of rodents. The livers, lungs, and small intestines of untreated rabbits and the livers of control rats were stored intact, or as microsomal suspensions, under liquid nitrogen at -196 degrees C. Aniline hydroxylase, aminopyrine demethylase, benzpyrene hydroxylase, biphenyl hydroxylase, NADPH-cytochrome c reductase, UDP-glucuronyltransferase activities, the microsomal content of cytochrome P-450, and the aniline- and benzphetamine-induced spectral changes were compared in fresh and stored preparations. Few significant changes in any of the above parameters resulted from storage of rabbit tissue preparations in liquid nitrogen for periods of up to 28 days. Pretreatment of rabbits with phenobarbital did not affect the stability of their stored microsomal preparations. Enzyme activities in the livers of untreated or 3-methylcholanthrene-pretreated rats were less stable to storage than in tissue preparations from rabbits stored under identical conditions. However, when rat hepatic microsomes were resuspended in KCl-HEPES supplemented with 1 mM EDTA before storage, enzyme activities were largely unaffected by freezing in liquid nitrogen."}
{"id": "PMID:10145", "title": "Role of blood flow in carbon monoxide- and hypoxic hypoxia-induced alterations in hexobarbital metabolism in rats.", "content": "The flow dependency of hepatic hexobarbital metabolism was examined in the isolated perfused rat liver. At low flow rates (0.5-1.0 ml/min/g of liver) hexobarbital clearance was found to depend on perfusion fluid flow, whereas at higher flow rates drug clearnace approached flow independence. Calculation of the in vivo hepatic blood flow rate suggested that hexobarbital metabolism in vivo should be highly dependent upon flow. Blood flow in the conscious rat was measured by use of radiolabeled microspheres during acute exposure to levels of hypoxic hypoxia (lowered pO2) or carbon monoxide which resulted in equal alterations in arterial oxyhemoglobin content (approximately 65% oxyhemoglobin). Hypoxic hypoxia (8% O2) caused a massive redistribution of flow away from the splanchnic area, resulting in a 45% decrease in hepatic blood flow. Carbon monoxide (500 ppm) was without significant effect on hepatic blood flow. These data would appear to explain the relatively greater inhibitory potency of hypoxic hypoxia on drug metabolism in vivo, since drug delivery to the liver is depressed by hypoxic hypoxia but unaffected by carbon monoxide exposure.", "contents": "Role of blood flow in carbon monoxide- and hypoxic hypoxia-induced alterations in hexobarbital metabolism in rats. The flow dependency of hepatic hexobarbital metabolism was examined in the isolated perfused rat liver. At low flow rates (0.5-1.0 ml/min/g of liver) hexobarbital clearance was found to depend on perfusion fluid flow, whereas at higher flow rates drug clearnace approached flow independence. Calculation of the in vivo hepatic blood flow rate suggested that hexobarbital metabolism in vivo should be highly dependent upon flow. Blood flow in the conscious rat was measured by use of radiolabeled microspheres during acute exposure to levels of hypoxic hypoxia (lowered pO2) or carbon monoxide which resulted in equal alterations in arterial oxyhemoglobin content (approximately 65% oxyhemoglobin). Hypoxic hypoxia (8% O2) caused a massive redistribution of flow away from the splanchnic area, resulting in a 45% decrease in hepatic blood flow. Carbon monoxide (500 ppm) was without significant effect on hepatic blood flow. These data would appear to explain the relatively greater inhibitory potency of hypoxic hypoxia on drug metabolism in vivo, since drug delivery to the liver is depressed by hypoxic hypoxia but unaffected by carbon monoxide exposure."}
{"id": "PMID:10146", "title": "The time course of tolmetin and its metabolites in the plasma of individual rats and mice.", "content": "Tolmetin, 1-methyl-(5-p-toluoyl)pyrrole-2-acetic acid, is a new, nonsteroidal, anti-inflammatory agent. After oral administration of tolmetin-14C to rats and mice, sequential microsamples of blood were obtained from the ophthalmic venous plexus via the orbital sinus. Plasma was collected after centrifugation, and microaliquots of each plasma sample were analyzed. The total radioactivity and thin-layer chromatographic assays used permitted quantitation of tolmetin, its dicarboxylic acid metabolite, and (by difference) all other metabolites collectively for each sample. Time-course data on plasma levels were obtained for individual rats and mice. The plasma elimination half-life of tolmetin was estimated at 0.67 +/- 0.13 hr (mean +/- SD) in male rats, 1.4 +/- 0.6 hr in female rats, 1.2 +/- 0.3 hr in male mice, and 1.0 +/- 0.0 hr in female mice. A one-compartment open model was used.", "contents": "The time course of tolmetin and its metabolites in the plasma of individual rats and mice. Tolmetin, 1-methyl-(5-p-toluoyl)pyrrole-2-acetic acid, is a new, nonsteroidal, anti-inflammatory agent. After oral administration of tolmetin-14C to rats and mice, sequential microsamples of blood were obtained from the ophthalmic venous plexus via the orbital sinus. Plasma was collected after centrifugation, and microaliquots of each plasma sample were analyzed. The total radioactivity and thin-layer chromatographic assays used permitted quantitation of tolmetin, its dicarboxylic acid metabolite, and (by difference) all other metabolites collectively for each sample. Time-course data on plasma levels were obtained for individual rats and mice. The plasma elimination half-life of tolmetin was estimated at 0.67 +/- 0.13 hr (mean +/- SD) in male rats, 1.4 +/- 0.6 hr in female rats, 1.2 +/- 0.3 hr in male mice, and 1.0 +/- 0.0 hr in female mice. A one-compartment open model was used."}
{"id": "PMID:10147", "title": "The urinary excretion profiles of naltrexone in man, monkey, rabbit, and rat.", "content": "A gas-chromatographic method has been developed for the simultaneous determination of naltrexone, alpha-naltrexol, and beta-naltrexol as trimethylsiyl derivatives. Analysis of urine from rabbit, monkey, and rat demonstrated that, like man, these species reduce naltrexone primarily to beta-naltrexol. In naltrexone maintenance patients receiving 125 mg po three times per week, an average of 37% of the dose was recovered in 48-hr urine as free naltrexone (0.8%), conjugated naltrexone (7.6%), free beta-naltrexol (16.8%), and conjugated beta-naltrexol (11.8%). Thirty-four percent of the dose appeared in 0-24 hr and 3% during 24-48 hr. The ratio of beta-naltrexol to naltrexone rose from 2 at 0-4 hr to 34-48 hr. Monkeys receiving a daily dose of 12 mg/kg po, chronically, excreted very little free beta-naltrexol and exhibited an apparent sex-related difference in excretion patterns, with females excreting more than twice as much total base as males. Rabbits given a dose of 30 mg/kg ip for 4 days excreted conjugated naltrexone as the predominant urinary metabolite, accounting for 80% of total base recovered in 24 hr. In rats receiving 100 mg/kg po, less than 1% of the administered dose could be accounted for in the 24-hr urine, indicating that although the beta-naltrexol is produced as a urinary metabolite, other means of disposition of the drug must exist. Thus, in man and the monkey, beta-naltrexol is the predominant and persistent urinary metabolite. Urinary excretion profiles of naltrexone differ greatly between species commonly examined for chronic toxicity studies.", "contents": "The urinary excretion profiles of naltrexone in man, monkey, rabbit, and rat. A gas-chromatographic method has been developed for the simultaneous determination of naltrexone, alpha-naltrexol, and beta-naltrexol as trimethylsiyl derivatives. Analysis of urine from rabbit, monkey, and rat demonstrated that, like man, these species reduce naltrexone primarily to beta-naltrexol. In naltrexone maintenance patients receiving 125 mg po three times per week, an average of 37% of the dose was recovered in 48-hr urine as free naltrexone (0.8%), conjugated naltrexone (7.6%), free beta-naltrexol (16.8%), and conjugated beta-naltrexol (11.8%). Thirty-four percent of the dose appeared in 0-24 hr and 3% during 24-48 hr. The ratio of beta-naltrexol to naltrexone rose from 2 at 0-4 hr to 34-48 hr. Monkeys receiving a daily dose of 12 mg/kg po, chronically, excreted very little free beta-naltrexol and exhibited an apparent sex-related difference in excretion patterns, with females excreting more than twice as much total base as males. Rabbits given a dose of 30 mg/kg ip for 4 days excreted conjugated naltrexone as the predominant urinary metabolite, accounting for 80% of total base recovered in 24 hr. In rats receiving 100 mg/kg po, less than 1% of the administered dose could be accounted for in the 24-hr urine, indicating that although the beta-naltrexol is produced as a urinary metabolite, other means of disposition of the drug must exist. Thus, in man and the monkey, beta-naltrexol is the predominant and persistent urinary metabolite. Urinary excretion profiles of naltrexone differ greatly between species commonly examined for chronic toxicity studies."}
{"id": "PMID:10148", "title": "The biotransformation of (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy) acetic acid (MK-196) in the chimpanzee.", "content": "The metabolism of a novel polyvalent saluretic agent (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196) was studied in the chimpanzee. Following oral administration, 50% of the radioactive dose was recovered in the urine in four days; 8-14% of the dose was excreted as unchanged drug. The fecal specimens accounted for 5-9% of the dose. Following intravenous administration an initial rapid elimination of drug from the plasma was observed [(t1/2)alpha approximately 0.4 hr, (t1/2)beta approximately 4 hr]. The data are consistent with the rapid elimination of radioactivity, approximately 30% of dose, in the urine during the first 24 hr, followed by a much slower rate of excretion of drug and metabolites. These findings are congruous with the high affinity (greater than 98%) of MK-196 and the major metabolite with plasma proteins. The urinary metabolites were isolated and identified by the following techniques: solvent extraction, column, thin-layer, and gas-liquid chromatography, derivatization, and mass and nuclear magnetic resonance spectroscopy. The major metabolite, which resulted from para-hydroxylation of the 2-phenyl substitutent, accounted for about 40% of the urinary radioactivity. Reduction of the ketone group, methylation of the p-hydroxy group, and additional phenyl ring hydroxylation were also shown to occur. There was no evidence for glucuronide formation nor did SKF-525-A inhibit the metabolism of the drug in the chimpanzee. Under conditions of induced metabolic alkalosis, the urinary levels of MK-196 increased from 11 to 40%. Probenecid and p-aminohippurate administered during metabolic alkalosis decreased the clearance of drug (40 to 15%).", "contents": "The biotransformation of (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy) acetic acid (MK-196) in the chimpanzee. The metabolism of a novel polyvalent saluretic agent (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196) was studied in the chimpanzee. Following oral administration, 50% of the radioactive dose was recovered in the urine in four days; 8-14% of the dose was excreted as unchanged drug. The fecal specimens accounted for 5-9% of the dose. Following intravenous administration an initial rapid elimination of drug from the plasma was observed [(t1/2)alpha approximately 0.4 hr, (t1/2)beta approximately 4 hr]. The data are consistent with the rapid elimination of radioactivity, approximately 30% of dose, in the urine during the first 24 hr, followed by a much slower rate of excretion of drug and metabolites. These findings are congruous with the high affinity (greater than 98%) of MK-196 and the major metabolite with plasma proteins. The urinary metabolites were isolated and identified by the following techniques: solvent extraction, column, thin-layer, and gas-liquid chromatography, derivatization, and mass and nuclear magnetic resonance spectroscopy. The major metabolite, which resulted from para-hydroxylation of the 2-phenyl substitutent, accounted for about 40% of the urinary radioactivity. Reduction of the ketone group, methylation of the p-hydroxy group, and additional phenyl ring hydroxylation were also shown to occur. There was no evidence for glucuronide formation nor did SKF-525-A inhibit the metabolism of the drug in the chimpanzee. Under conditions of induced metabolic alkalosis, the urinary levels of MK-196 increased from 11 to 40%. Probenecid and p-aminohippurate administered during metabolic alkalosis decreased the clearance of drug (40 to 15%)."}
{"id": "PMID:10152", "title": "[A new immunochemical tube test for pregnancy, using the principle of the latex-agglutination inhibition reaction. I. Basic studies (author's transl)].", "content": "In a joint study of five laboratories the immunochemical tube test for pregnancy 'Roche', which uses the principle of the latex-agglutination inhibition test, was examined. A total of 1117 samples, complemented by a number of laboratory studies, proved that the test is specific, reproducible and low in interference with a sensitivity of 900-1000 U/l HCG. It is a simple test, the results can be easily read after 90 minutes. pH of the urine sample, protein, urea or calcium content, presence of oral contraceptives, detergents, disinfectants or organic solvents cause no or very little interference.", "contents": "[A new immunochemical tube test for pregnancy, using the principle of the latex-agglutination inhibition reaction. I. Basic studies (author's transl)]. In a joint study of five laboratories the immunochemical tube test for pregnancy 'Roche', which uses the principle of the latex-agglutination inhibition test, was examined. A total of 1117 samples, complemented by a number of laboratory studies, proved that the test is specific, reproducible and low in interference with a sensitivity of 900-1000 U/l HCG. It is a simple test, the results can be easily read after 90 minutes. pH of the urine sample, protein, urea or calcium content, presence of oral contraceptives, detergents, disinfectants or organic solvents cause no or very little interference."}
{"id": "PMID:10149", "title": "The physiological disposition of the uricosuric-saluretic agent (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196) in the rat, dog, and monkey.", "content": "The physiological disposition of a new saluretic-uricosuric agent, (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196), was studied in the rat, dog, and monkey. MK-196 was well absorbed and showed minimal metabolism in these species. Peak plasma levels of radioactivity and drug occurred 0.5-2 hr after oral administration at a dose of 2.5 mg/kg. Essentially all of the radioactivity present in the plasma during the first day was intact MK-196. Following a single dose, a long terminal half-life for plasma radioactivity was observed in the dog (approximately 68 hr) and monkey (approximately 105 hr). The chronic administration of MK-196 to dogs resulted in a dose-related plasma profile and showed no tendency to increase or decrease with dosing. However, upon repeated drug administration to monkeys, the plasma levels of drug increased and then decreased, possibly due to hypochloremia and secondary metabolic alkalosis. Fecal excretion was the predominant route of tracer elimination in the dog (approximately 80%) and rat (approximately 94%), whereas the monkey eliminated the majority of the dose (approximately 60%) via the urine. Minimal metabolism was noted in the three lower species; most of the urinary, plasma, and fecal radioactivity was accounted for as intact drug and its glucuronide conjugate. Three minor metabolites, which were present in dog bile, plasma, and urine, were characterized as: (l,7-dichloro-1alpha-hydroxy-2-methyl-2-phenyl-5-indanyloxy)acetic acid, I; (6,7-dichloro-2-(4-hydroxyphenyl)-2-methyl-2-oxo-5-indanyloxy)acetic acid, II; and 2-methyl-2-phenyl-5-hydroxy-6,7-dichloro-1-indanone, III. The monkey urine and plasma also contained small amounts of II.", "contents": "The physiological disposition of the uricosuric-saluretic agent (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196) in the rat, dog, and monkey. The physiological disposition of a new saluretic-uricosuric agent, (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196), was studied in the rat, dog, and monkey. MK-196 was well absorbed and showed minimal metabolism in these species. Peak plasma levels of radioactivity and drug occurred 0.5-2 hr after oral administration at a dose of 2.5 mg/kg. Essentially all of the radioactivity present in the plasma during the first day was intact MK-196. Following a single dose, a long terminal half-life for plasma radioactivity was observed in the dog (approximately 68 hr) and monkey (approximately 105 hr). The chronic administration of MK-196 to dogs resulted in a dose-related plasma profile and showed no tendency to increase or decrease with dosing. However, upon repeated drug administration to monkeys, the plasma levels of drug increased and then decreased, possibly due to hypochloremia and secondary metabolic alkalosis. Fecal excretion was the predominant route of tracer elimination in the dog (approximately 80%) and rat (approximately 94%), whereas the monkey eliminated the majority of the dose (approximately 60%) via the urine. Minimal metabolism was noted in the three lower species; most of the urinary, plasma, and fecal radioactivity was accounted for as intact drug and its glucuronide conjugate. Three minor metabolites, which were present in dog bile, plasma, and urine, were characterized as: (l,7-dichloro-1alpha-hydroxy-2-methyl-2-phenyl-5-indanyloxy)acetic acid, I; (6,7-dichloro-2-(4-hydroxyphenyl)-2-methyl-2-oxo-5-indanyloxy)acetic acid, II; and 2-methyl-2-phenyl-5-hydroxy-6,7-dichloro-1-indanone, III. The monkey urine and plasma also contained small amounts of II."}
{"id": "PMID:10153", "title": "Antianxiety drugs: clinical pharmacology and therapeutic use.", "content": "It is difficult to choose among the many drugs advocated for treating anxiety symptoms. The barbiturates were the most commonly used antianxiety agents until recently but are being superseded by the benzodiazepines. The latter are more effective than the barbiturates as shown in comparative clinical trials, they are safer in overdosage (deliberate or accidental), and they are somewhat less likely to induce dependence. The barbiturates have the additional drawback of interfering with the action of other drugs by inducing liver microsomal (oxidising) drug metabolising enzymes. The major tranquilisers (neuroleptics or antipsychotics) are often of value in low dosage in patients with a previous history of dependence on alcohol, the barbiturates or the benzodiazepines. Tricyclic antidepressants are the treatment of choice in anxious and depressed patients and monoamine oxidase inhibitors may be helpful in phobic patients. The beta-adrenoreceptor blocking agents such as propranolol often ameliorate somatic symptoms such as palpitations and tremor. In the treatment of anxious patients it is important to remove causes for anxiety and to limit any course of drug treatment to a finite period. Both dosage level and dosage interval should be flexible. Benzodiazepines remain the drug treatment of choice.", "contents": "Antianxiety drugs: clinical pharmacology and therapeutic use. It is difficult to choose among the many drugs advocated for treating anxiety symptoms. The barbiturates were the most commonly used antianxiety agents until recently but are being superseded by the benzodiazepines. The latter are more effective than the barbiturates as shown in comparative clinical trials, they are safer in overdosage (deliberate or accidental), and they are somewhat less likely to induce dependence. The barbiturates have the additional drawback of interfering with the action of other drugs by inducing liver microsomal (oxidising) drug metabolising enzymes. The major tranquilisers (neuroleptics or antipsychotics) are often of value in low dosage in patients with a previous history of dependence on alcohol, the barbiturates or the benzodiazepines. Tricyclic antidepressants are the treatment of choice in anxious and depressed patients and monoamine oxidase inhibitors may be helpful in phobic patients. The beta-adrenoreceptor blocking agents such as propranolol often ameliorate somatic symptoms such as palpitations and tremor. In the treatment of anxious patients it is important to remove causes for anxiety and to limit any course of drug treatment to a finite period. Both dosage level and dosage interval should be flexible. Benzodiazepines remain the drug treatment of choice."}
{"id": "PMID:10150", "title": "Biliary copper excretion in the rat is enhanced by spironolactone.", "content": "Tissue distribution and excretion (urinary, fecal, and biliary) of an intravenous bolus of 64Cu(NO3)2 were measured in rats pretreated with spironolactone and in controls. Intact animals pretreated with spironolactone excreted 10% more of a standard intravenous injection of copper in the first 24 hr than did controls. At the end of that time, kidney, red blood cell, and serum copper levels all were similar for the two groups, but liver copper concentrations were higher in controls. During the 1st hr after copper injection, plasma copper levels tended to fall more rapidly in pretreated animals, whereas liver copper concentrations increased more rapidly; red blood cell copper concentrations were not higher in animals given spironolactone. Pretreated animals excreted significantly more copper in the bile during the first 2 hr after 64Cu(NO3)2 injection, and had higher hepatic copper levels at 3 hr.", "contents": "Biliary copper excretion in the rat is enhanced by spironolactone. Tissue distribution and excretion (urinary, fecal, and biliary) of an intravenous bolus of 64Cu(NO3)2 were measured in rats pretreated with spironolactone and in controls. Intact animals pretreated with spironolactone excreted 10% more of a standard intravenous injection of copper in the first 24 hr than did controls. At the end of that time, kidney, red blood cell, and serum copper levels all were similar for the two groups, but liver copper concentrations were higher in controls. During the 1st hr after copper injection, plasma copper levels tended to fall more rapidly in pretreated animals, whereas liver copper concentrations increased more rapidly; red blood cell copper concentrations were not higher in animals given spironolactone. Pretreated animals excreted significantly more copper in the bile during the first 2 hr after 64Cu(NO3)2 injection, and had higher hepatic copper levels at 3 hr."}
{"id": "PMID:10155", "title": "An equine cryptorchid with testicular and ovarian tissues.", "content": "Cytogenetic and histological studies were carried out on an intersex horse which was diagnosed clinically as a cryptorchid. Surgery confirmed the horse to be a bilateral abdominal cryptorchid and histological examination revealed ovarian tissue associated with the left epididymis. Chromosome analysis of cultured cells from testicular tissue, ovarian tissue and skin revealed 64-XX and 64-XY make-up, the left gonad containing a greater preponderance of XX cells over XY cells. The external characteristics and behaviour of the horse were indistinguishable from that of a \"routine\" cryptorchid. Other cases of equine intersexes are reviewed and theories for the discrepancies between genetic, gonadal and phenotypic sex are discussed.", "contents": "An equine cryptorchid with testicular and ovarian tissues. Cytogenetic and histological studies were carried out on an intersex horse which was diagnosed clinically as a cryptorchid. Surgery confirmed the horse to be a bilateral abdominal cryptorchid and histological examination revealed ovarian tissue associated with the left epididymis. Chromosome analysis of cultured cells from testicular tissue, ovarian tissue and skin revealed 64-XX and 64-XY make-up, the left gonad containing a greater preponderance of XX cells over XY cells. The external characteristics and behaviour of the horse were indistinguishable from that of a \"routine\" cryptorchid. Other cases of equine intersexes are reviewed and theories for the discrepancies between genetic, gonadal and phenotypic sex are discussed."}
{"id": "PMID:10151", "title": "The secretion of methadone and its major metabolite in the gastric juice of humans: comparison with blood and salivary concentrations.", "content": "Four healthy subjects and four addicts on high daily maintenance doses of methadone each received a parenteral dose of methadone hydrochloride following an overnight fast. The concentration of methadone in blood was compared with that in the gastric juice obtained over 8 hr by continuous low-pressure suction via a nasogastric tube. The concentration in the gastric juice was 25-200 times that measured at the same time in the blood. Thus, 8 hr after the injection mean blood concentrations of 28 and 210 ng of methadone per ml were recorded in the normal subjects and the addicts, respectively. The corresponding concentrations in gastric juice were 2,200 ng/ml and 18,000 ng/ml, respectively. In the normal subjects about 2% of the administered dose was recovered in the gastric juice in 8 hr, whereas in addicts about 7% was recovered. The greater recovery of methadone from the addicts appears to be the result of the larger volume of gastric juice recovered from the latter subjects. Methadone was also excreted in the saliva of both groups of subjects. In addicts, salivary concentrations were often 10 times those recorded in the blood. The N-monodemethylated metabolite of methadone was identified in the gastric juice of addicts by gas chromatography and mass spectrometry.", "contents": "The secretion of methadone and its major metabolite in the gastric juice of humans: comparison with blood and salivary concentrations. Four healthy subjects and four addicts on high daily maintenance doses of methadone each received a parenteral dose of methadone hydrochloride following an overnight fast. The concentration of methadone in blood was compared with that in the gastric juice obtained over 8 hr by continuous low-pressure suction via a nasogastric tube. The concentration in the gastric juice was 25-200 times that measured at the same time in the blood. Thus, 8 hr after the injection mean blood concentrations of 28 and 210 ng of methadone per ml were recorded in the normal subjects and the addicts, respectively. The corresponding concentrations in gastric juice were 2,200 ng/ml and 18,000 ng/ml, respectively. In the normal subjects about 2% of the administered dose was recovered in the gastric juice in 8 hr, whereas in addicts about 7% was recovered. The greater recovery of methadone from the addicts appears to be the result of the larger volume of gastric juice recovered from the latter subjects. Methadone was also excreted in the saliva of both groups of subjects. In addicts, salivary concentrations were often 10 times those recorded in the blood. The N-monodemethylated metabolite of methadone was identified in the gastric juice of addicts by gas chromatography and mass spectrometry."}
{"id": "PMID:10157", "title": "Red cell hemoglobin, hydrogen ion and electrolyte concentrations during exercise in trained and untrained subjects.", "content": "Red cell concentrations of hemoglobin (MCHC), H+, Na+, K+, Mg++, cl- were measured in femoral venous blood of six untrained (UT), six endurance trained (TR) and three semitrained (ST) subjects during graded increasing work (4, 8, 12, 18 and 24 mkp/s, 10-15 min on each step) on a bicycle ergometer. Before exercise no significant differences were detected for the measured variables when comparing UT and TR. During exercise MCHC, [Na+], [K+] and [Mg++] remained constant indicating lack of water shift into the erythrocytes in spite of a marked acidosis (lowest pH Blood value 7.225). This lack resulted from an elevated extracellular osmolality. [H+]Ery and [Cl-]Ery maximally increased by 2.0 X 10(-8) eq/kg H2O and 10 meq/l, respectively. The change was markedly greater in UT than in TR at equal load. However, if [H+] Ery and [Cl-] Ery were related to pH of whole blood, differences between groups, almost disappeared and the ions were distributed as predictable from in vitro experiments (Fitzsimmons and Sendroy, 1961). Behaviour of H+ and Cl- may be of importance for oxygen dissociation under in vivo conditions.", "contents": "Red cell hemoglobin, hydrogen ion and electrolyte concentrations during exercise in trained and untrained subjects. Red cell concentrations of hemoglobin (MCHC), H+, Na+, K+, Mg++, cl- were measured in femoral venous blood of six untrained (UT), six endurance trained (TR) and three semitrained (ST) subjects during graded increasing work (4, 8, 12, 18 and 24 mkp/s, 10-15 min on each step) on a bicycle ergometer. Before exercise no significant differences were detected for the measured variables when comparing UT and TR. During exercise MCHC, [Na+], [K+] and [Mg++] remained constant indicating lack of water shift into the erythrocytes in spite of a marked acidosis (lowest pH Blood value 7.225). This lack resulted from an elevated extracellular osmolality. [H+]Ery and [Cl-]Ery maximally increased by 2.0 X 10(-8) eq/kg H2O and 10 meq/l, respectively. The change was markedly greater in UT than in TR at equal load. However, if [H+] Ery and [Cl-] Ery were related to pH of whole blood, differences between groups, almost disappeared and the ions were distributed as predictable from in vitro experiments (Fitzsimmons and Sendroy, 1961). Behaviour of H+ and Cl- may be of importance for oxygen dissociation under in vivo conditions."}
{"id": "PMID:10158", "title": "Binding of carbon monoxide to alpha-hemocyanin and beta-hemocyanin from Helix pomatia.", "content": "The binding of carbon monoxide to alpha and beta-hemocyanin from the snail Helix pomatia was studied under equilibrium conditions. Homotropic interactions upon carbon monoxide binding were much weaker than upon the binding of oxygen. Heterotropic interactions (Bohr effect and calcium-ion effect), however, were just as strong as in the case of the binding of oxygen. For alpha-hemocyanin a linkage has been observed between the binding of carbon monoxide and a change in quaternary structure of the protein.", "contents": "Binding of carbon monoxide to alpha-hemocyanin and beta-hemocyanin from Helix pomatia. The binding of carbon monoxide to alpha and beta-hemocyanin from the snail Helix pomatia was studied under equilibrium conditions. Homotropic interactions upon carbon monoxide binding were much weaker than upon the binding of oxygen. Heterotropic interactions (Bohr effect and calcium-ion effect), however, were just as strong as in the case of the binding of oxygen. For alpha-hemocyanin a linkage has been observed between the binding of carbon monoxide and a change in quaternary structure of the protein."}
{"id": "PMID:10159", "title": "Studies on the kinetic effects of adenosine-3':5'-monophosphate-dependent phosphorylation of purified pig-liver pyruvate kinase type L.", "content": "The effect of cyclic-AMP-dependent phosphorylation on the activity of isolated pig liver pyruvate kinase was studied. It was found that the major kinetic effect of the phosphorylation was to reduce the affinity for the substrate phosphoenolpyruvate, K0.5 for this substrate increasing from 0.3 to 0.9 mM upon phosphorylation. The cooperative effect with phosphoenolpyruvate was enhanced, the Hill constant nH increasing concomitantly from 1.1 to 1.5. V was unaltered. The change in activity occurred in parallel with the phosphate incorporation, except during the initial part of the reaction, when inactivation was correspondingly slower. The affinity for the second substrate ADP was unchanged, with an apparent Km of 0.3 mM at saturating concentration of phosphoenolpyruvate. Likewise, the requirement for potassium was unaffected, whereas the phosphoenzyme required a higher concentration of magnesium ions for maximal activity, compared with the control enzyme. The inhibitory effect of the phosphorylation was counteracted by positive effectors, fructose 1,6-biphosphate in micromolar concentrations completely activated the phosphoenzyme, resulting in an enzyme with properties similar to the fructose 1,6-biphosphate-activated unphosphorylated enzyme, with K0.5 for phosphoenolpyruvate about 0.025 mM and with a Hill constant of 1.1. Hydrogen ions were also effective in activating the phosphoenzyme. Thus, when pH was lowered from 8 to 6.5 the inhibition due to phosphorylation was abolished. The phosphoenzyme was sensitive to further inhibition by negative effectors such as ATP and alanine. 2 mM ATP increased K0.5 for phosphoenolpyruvate to 1.5 mM and nH to 2.3. The corresponding values with alanine were 1.3 mM and 1.9. Phosphorylation is thought to be an additional mechanism of inhibition of the enzyme under gluconeogenetic conditions.", "contents": "Studies on the kinetic effects of adenosine-3':5'-monophosphate-dependent phosphorylation of purified pig-liver pyruvate kinase type L. The effect of cyclic-AMP-dependent phosphorylation on the activity of isolated pig liver pyruvate kinase was studied. It was found that the major kinetic effect of the phosphorylation was to reduce the affinity for the substrate phosphoenolpyruvate, K0.5 for this substrate increasing from 0.3 to 0.9 mM upon phosphorylation. The cooperative effect with phosphoenolpyruvate was enhanced, the Hill constant nH increasing concomitantly from 1.1 to 1.5. V was unaltered. The change in activity occurred in parallel with the phosphate incorporation, except during the initial part of the reaction, when inactivation was correspondingly slower. The affinity for the second substrate ADP was unchanged, with an apparent Km of 0.3 mM at saturating concentration of phosphoenolpyruvate. Likewise, the requirement for potassium was unaffected, whereas the phosphoenzyme required a higher concentration of magnesium ions for maximal activity, compared with the control enzyme. The inhibitory effect of the phosphorylation was counteracted by positive effectors, fructose 1,6-biphosphate in micromolar concentrations completely activated the phosphoenzyme, resulting in an enzyme with properties similar to the fructose 1,6-biphosphate-activated unphosphorylated enzyme, with K0.5 for phosphoenolpyruvate about 0.025 mM and with a Hill constant of 1.1. Hydrogen ions were also effective in activating the phosphoenzyme. Thus, when pH was lowered from 8 to 6.5 the inhibition due to phosphorylation was abolished. The phosphoenzyme was sensitive to further inhibition by negative effectors such as ATP and alanine. 2 mM ATP increased K0.5 for phosphoenolpyruvate to 1.5 mM and nH to 2.3. The corresponding values with alanine were 1.3 mM and 1.9. Phosphorylation is thought to be an additional mechanism of inhibition of the enzyme under gluconeogenetic conditions."}
{"id": "PMID:10160", "title": "Efficiency of oxidative phosphorylation and energy dissipation by H+ ion recycling in rat-liver mitochondrial metabolizing pyruvate.", "content": "A method was developed for the calculation of metabolic fluxes through individual enzymatic reactions of pyruvate metabolism including the citric acid cycle in rat liver mitochondrial incubated at metabolic states between state 4 and state 3. This method is based on the measurement of the specific radioactivities of the products formed from [2-14C]pyruvate. With this procedure the energy balance of mitochondria incubated in the presence of [2-14C]pyruvate, ATP, bicarbonate and phosphate at different ATP/ADP ratios in the medium was calculated. The ATP/ADP ratios were maintained at a steady state with creatine kinase plus creatine as a phosphoryl acceptor. The calculations revealed that by adding increasing concentrations of creatine up to 20 mM the energy dissipated by the mitochondria decreased but showed a local maximum at 13mM creatine. Omission of bicarbonate from the medium led to a shift of this maximum. When energy dissipation was minimal the overall P/O ratio was maximal. The amount of energy dissipated was paralleled by the magnitude of the pH gradient across the inner membrane. From these results it was concluded that the recycling of H+ ions which consists of a passive leakage of H+ ions into the matrix and an active extrusion of these ions out of this compartment, is an important energy dissipating process. The H+ ion recycling is thus one of the processes which give rise to the state 4 respiration in mitochondria.", "contents": "Efficiency of oxidative phosphorylation and energy dissipation by H+ ion recycling in rat-liver mitochondrial metabolizing pyruvate. A method was developed for the calculation of metabolic fluxes through individual enzymatic reactions of pyruvate metabolism including the citric acid cycle in rat liver mitochondrial incubated at metabolic states between state 4 and state 3. This method is based on the measurement of the specific radioactivities of the products formed from [2-14C]pyruvate. With this procedure the energy balance of mitochondria incubated in the presence of [2-14C]pyruvate, ATP, bicarbonate and phosphate at different ATP/ADP ratios in the medium was calculated. The ATP/ADP ratios were maintained at a steady state with creatine kinase plus creatine as a phosphoryl acceptor. The calculations revealed that by adding increasing concentrations of creatine up to 20 mM the energy dissipated by the mitochondria decreased but showed a local maximum at 13mM creatine. Omission of bicarbonate from the medium led to a shift of this maximum. When energy dissipation was minimal the overall P/O ratio was maximal. The amount of energy dissipated was paralleled by the magnitude of the pH gradient across the inner membrane. From these results it was concluded that the recycling of H+ ions which consists of a passive leakage of H+ ions into the matrix and an active extrusion of these ions out of this compartment, is an important energy dissipating process. The H+ ion recycling is thus one of the processes which give rise to the state 4 respiration in mitochondria."}
{"id": "PMID:10161", "title": "Membrane-bound DD-carboxypeptidase and transpeptidase activities from Bacillus megaterium KM at pH 7. General properties, substrate specificity and inhibition by beta-lactam antibiotics.", "content": "1. The membranes from Bacillus megaterium KM contained a DD-carboxypeptidase with optimum activity under the following conditions: pH 7; ionic strength, 1.3 M; temperature, 40 degrees C and below 20 degrees C. It did not require any divalent cation, but was inactivated by Cu2+ and Hg2+. It was stimulated by 2-mercaptoethanol and low concentrations of p-chloromercuribenzoate. 2. The membrane preparation also catalyzed a simple transpeptidation reaction using as carboxyl acceptors D-alanine or glycine. 3. The conditions for optimum activity, temperature-inactivation, temperature-dependence of the activity, carboxyl donor specificity, sensitivity to beta-lactam antibiotics, and insensitivity to potential peptide inhibitors of both enzyme activities, was identical. The DD-carboxypeptidase showed inhibition by D-alanine and Ac2-L-Lys-D-Ala. 4. The inhibition by beta-lactam antibiotic was reversible for both enzymic activities and the time-dependence for their recovery was identical. 5. The DD-carboxypeptidase was very sensitive to changes in the configuration and size of the side-chains of the C-terminal dipeptide of the substrate. Amino acid residues at the C-terminus that precluded the peptide from being a DD-carboxypeptidase substrate were not acceptors in the transpeptidation reaction. Dipeptides were not acceptors for the 'model transpeptidase'. 6. It is suggested that both activities are catalysed by the same enzyme molecule, whose physiological role is not the formation of peptide crosslinks during peptidoglycan biosynthesis.", "contents": "Membrane-bound DD-carboxypeptidase and transpeptidase activities from Bacillus megaterium KM at pH 7. General properties, substrate specificity and inhibition by beta-lactam antibiotics. 1. The membranes from Bacillus megaterium KM contained a DD-carboxypeptidase with optimum activity under the following conditions: pH 7; ionic strength, 1.3 M; temperature, 40 degrees C and below 20 degrees C. It did not require any divalent cation, but was inactivated by Cu2+ and Hg2+. It was stimulated by 2-mercaptoethanol and low concentrations of p-chloromercuribenzoate. 2. The membrane preparation also catalyzed a simple transpeptidation reaction using as carboxyl acceptors D-alanine or glycine. 3. The conditions for optimum activity, temperature-inactivation, temperature-dependence of the activity, carboxyl donor specificity, sensitivity to beta-lactam antibiotics, and insensitivity to potential peptide inhibitors of both enzyme activities, was identical. The DD-carboxypeptidase showed inhibition by D-alanine and Ac2-L-Lys-D-Ala. 4. The inhibition by beta-lactam antibiotic was reversible for both enzymic activities and the time-dependence for their recovery was identical. 5. The DD-carboxypeptidase was very sensitive to changes in the configuration and size of the side-chains of the C-terminal dipeptide of the substrate. Amino acid residues at the C-terminus that precluded the peptide from being a DD-carboxypeptidase substrate were not acceptors in the transpeptidation reaction. Dipeptides were not acceptors for the 'model transpeptidase'. 6. It is suggested that both activities are catalysed by the same enzyme molecule, whose physiological role is not the formation of peptide crosslinks during peptidoglycan biosynthesis."}
{"id": "PMID:10162", "title": "Kinetic investigation of the staphylococcal protease-catalyzed hydrolysis of synthetic substrates.", "content": "In investigating the staphylococcal protease-catalyzed hydrolysis of N-tert-butoxycarbonyl-L-glutamate alpha-phenyl ester, N-benzyloxycarbonyl-L-glutamate alpha-phenyl ester and N-benzyloxycarbonyl-L-glutamate alpha-p-nitroanilide, we obtained kinetic evidence consistent with the formation of an acyl-enzyme intermediate. We found that addition of a nucleophile, such as methanol, led to the partition of the common acyl-enzyme intermediate between water and the alcohol. With N-benzyl-oxycarbonyl-L-glutamate alpha-phenyl ester, a specific ester substrate, deacylation was shown to be the rate-limiting step. By studying the kcat/Km ratio of these hydrolyses as a function of pH, we have shown that two ionizable groups on the enzyme are essential to the catalytic process. One of these groups has a pK of 6.58 and the other, a pK of 8.25. The assignment of these pK values is discussed in connection with the known features of the serine proteinase reaction mechanism. In addition, monovalent anions were shown to inhibit staphylococcal protease hydrolyses. They seem to compete with the negative charge of the substrate, thus inhibiting its binding on the enzyme molecule. Finally we compared the kinetic parameters obtained with five proteases isolated from different strains of Staphylococcus aureus.", "contents": "Kinetic investigation of the staphylococcal protease-catalyzed hydrolysis of synthetic substrates. In investigating the staphylococcal protease-catalyzed hydrolysis of N-tert-butoxycarbonyl-L-glutamate alpha-phenyl ester, N-benzyloxycarbonyl-L-glutamate alpha-phenyl ester and N-benzyloxycarbonyl-L-glutamate alpha-p-nitroanilide, we obtained kinetic evidence consistent with the formation of an acyl-enzyme intermediate. We found that addition of a nucleophile, such as methanol, led to the partition of the common acyl-enzyme intermediate between water and the alcohol. With N-benzyl-oxycarbonyl-L-glutamate alpha-phenyl ester, a specific ester substrate, deacylation was shown to be the rate-limiting step. By studying the kcat/Km ratio of these hydrolyses as a function of pH, we have shown that two ionizable groups on the enzyme are essential to the catalytic process. One of these groups has a pK of 6.58 and the other, a pK of 8.25. The assignment of these pK values is discussed in connection with the known features of the serine proteinase reaction mechanism. In addition, monovalent anions were shown to inhibit staphylococcal protease hydrolyses. They seem to compete with the negative charge of the substrate, thus inhibiting its binding on the enzyme molecule. Finally we compared the kinetic parameters obtained with five proteases isolated from different strains of Staphylococcus aureus."}
{"id": "PMID:10164", "title": "Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy.", "content": "Amino acid concentrations were determined in plasma, whole blood, cerebrospinal fluid and brain tissue of 45 patients with grade 3 or 4 coma due to fulminant hepatic failure. The concentration of 15 of the 19 amino acids determined were significantly increased in blood and the increases were greatest for the amino acids concerned with neurotransmitter metabolism. There was no correlation, however, between the plasma concentration of these amino acids and changes in the grade of hepatic coma. The plasma concentrations of the branched chain amino acids were normal except in those patients who subsequently recovered in whom levels were slightly decreased. Phenylalanine- tyrosine and methionine were among the 15 out of 18 amino acids which were significantly increased in cerebrospinal fluid and among the 15 out of 21 amino acids which were significantly increased in the brain. The increase in tryptophan was associated with a significant elevation in brain 5-hydroxyindoleacetic acid concentration suggesting an increase in 5-hydroxytryptamine turnover in hepatic coma. Brain to plasma ratios of most amino acids in hepatic coma patients were similar to control subjects suggesting that plasma concentration is the main factor controlling the cerebral concentration. However, for the branched chain amino acids, cerebrospinal fluid and brain concentrations were increased when plasma concentrations were normal suggesting an increase in brain uptake.", "contents": "Plasma and brain amino acids in fulminant hepatic failure and their relationship to hepatic encephalopathy. Amino acid concentrations were determined in plasma, whole blood, cerebrospinal fluid and brain tissue of 45 patients with grade 3 or 4 coma due to fulminant hepatic failure. The concentration of 15 of the 19 amino acids determined were significantly increased in blood and the increases were greatest for the amino acids concerned with neurotransmitter metabolism. There was no correlation, however, between the plasma concentration of these amino acids and changes in the grade of hepatic coma. The plasma concentrations of the branched chain amino acids were normal except in those patients who subsequently recovered in whom levels were slightly decreased. Phenylalanine- tyrosine and methionine were among the 15 out of 18 amino acids which were significantly increased in cerebrospinal fluid and among the 15 out of 21 amino acids which were significantly increased in the brain. The increase in tryptophan was associated with a significant elevation in brain 5-hydroxyindoleacetic acid concentration suggesting an increase in 5-hydroxytryptamine turnover in hepatic coma. Brain to plasma ratios of most amino acids in hepatic coma patients were similar to control subjects suggesting that plasma concentration is the main factor controlling the cerebral concentration. However, for the branched chain amino acids, cerebrospinal fluid and brain concentrations were increased when plasma concentrations were normal suggesting an increase in brain uptake."}
{"id": "PMID:10165", "title": "Serum concentrations of methaqualone after repeated oral doses of a combination formulation to human subjects.", "content": "Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 mug/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and thereafter more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 mug/ml; 1.5 mug/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 mug/ml - 0.6 mug/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.", "contents": "Serum concentrations of methaqualone after repeated oral doses of a combination formulation to human subjects. Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 mug/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and thereafter more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 mug/ml; 1.5 mug/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 mug/ml - 0.6 mug/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation."}
{"id": "PMID:10166", "title": "The immunological properties of haptens coupled to thymus-independent carrier molecules. III. The role of the immunogenicity and mitogenicity of the carrier in the induction of primary IgM anti-hapten responses.", "content": "Hapten (DNP-lys) conjugates of two putatively nonimmunogenic polymers, hyalutonic acid and poly-gamma-D-glutamic acid, induce significant primary IgM anti-DNP responses in C3H mice. Preparations of various immunogenic (Type 3 pneumococcal polysaccharide (SIII), levan, E. coli lipopolysaccharide) and nonimmunogenic (hyaluronic acid and poly-glutamic acid) polymers were tested for their ability to act as polyclonal mitogens in vitro. In serum-containing spleen cell cultures, only lipopolysaccharide stimulated substantial cell proliferation. In serum-free medium, and using high specific activity [3H]thymidine, lipopolysaccharide, levan, SIII and to a lesser degree hyaluronic acid induced significant thymidine incorporation. However, under the latter conditions cell survival and proliferation were much less impressive. There was no apparent correlation between the capacity of various polymers to induce lymphocyte proliferation and their \"potency\" as carriers for the generation of a primary IgM anti-DNP response. Furthermore while low doses of lipopolysaccharide elicited \"polyclonal\" antibody formation in vivo, high doses of SIII, levan and hyaluronic acid did not. These results indicate that T cell-independent B cell triggering is dependent on the polymeric nature of the antigen, and that polymers need not be immunogenic or mitogenic to act as carriers for the induction of primary IgM anti-hapten antibody responses.", "contents": "The immunological properties of haptens coupled to thymus-independent carrier molecules. III. The role of the immunogenicity and mitogenicity of the carrier in the induction of primary IgM anti-hapten responses. Hapten (DNP-lys) conjugates of two putatively nonimmunogenic polymers, hyalutonic acid and poly-gamma-D-glutamic acid, induce significant primary IgM anti-DNP responses in C3H mice. Preparations of various immunogenic (Type 3 pneumococcal polysaccharide (SIII), levan, E. coli lipopolysaccharide) and nonimmunogenic (hyaluronic acid and poly-glutamic acid) polymers were tested for their ability to act as polyclonal mitogens in vitro. In serum-containing spleen cell cultures, only lipopolysaccharide stimulated substantial cell proliferation. In serum-free medium, and using high specific activity [3H]thymidine, lipopolysaccharide, levan, SIII and to a lesser degree hyaluronic acid induced significant thymidine incorporation. However, under the latter conditions cell survival and proliferation were much less impressive. There was no apparent correlation between the capacity of various polymers to induce lymphocyte proliferation and their \"potency\" as carriers for the generation of a primary IgM anti-DNP response. Furthermore while low doses of lipopolysaccharide elicited \"polyclonal\" antibody formation in vivo, high doses of SIII, levan and hyaluronic acid did not. These results indicate that T cell-independent B cell triggering is dependent on the polymeric nature of the antigen, and that polymers need not be immunogenic or mitogenic to act as carriers for the induction of primary IgM anti-hapten antibody responses."}
{"id": "PMID:10167", "title": "B cell tolerance induced by polymeric antigens. I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo.", "content": "Hapten [2,4-dinitrophenyl (DNP)]-specific tolerance was induced in nonimmune or DNP-hemocyanin (DNP-KLH) primed mice by administering hapten-conjugated type 3 pneumococcal polysaccharide (DNP-lys-S3). The dose of DNP-lys2.5-S3 required to suppress the primary anti-DNP antibody responses was approximately ten times higher than that required to suppress the secondary response. Large doses of lightly substituted antigen (DNP-lys0.6-S3) had no effect on primary antibody responses, while small doses of this conjugate suppressed 90-95% of the secondary response. The conclusion from this (presumably B cell) tolerance model is that B lymphocytes \"mature\" in their susceptibility to tolerization following primary contact with immunogen, since primed cells are inactivated by lower doses of tolerogen, and by tolerogen with lower epitope density, than nonimmune B cells. These and other data suggest that the tolerance threshold of B lymphocytes is related to their state of differentiation, and especially to their antigen-binding characteristics.", "contents": "B cell tolerance induced by polymeric antigens. I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo. Hapten [2,4-dinitrophenyl (DNP)]-specific tolerance was induced in nonimmune or DNP-hemocyanin (DNP-KLH) primed mice by administering hapten-conjugated type 3 pneumococcal polysaccharide (DNP-lys-S3). The dose of DNP-lys2.5-S3 required to suppress the primary anti-DNP antibody responses was approximately ten times higher than that required to suppress the secondary response. Large doses of lightly substituted antigen (DNP-lys0.6-S3) had no effect on primary antibody responses, while small doses of this conjugate suppressed 90-95% of the secondary response. The conclusion from this (presumably B cell) tolerance model is that B lymphocytes \"mature\" in their susceptibility to tolerization following primary contact with immunogen, since primed cells are inactivated by lower doses of tolerogen, and by tolerogen with lower epitope density, than nonimmune B cells. These and other data suggest that the tolerance threshold of B lymphocytes is related to their state of differentiation, and especially to their antigen-binding characteristics."}
{"id": "PMID:10168", "title": "B cell tolerance induced by polymeric antigens. II. Effects of tolerance on hapten-binding lymphocyte levels in primary and secondary antibody responses.", "content": "Tolerogenic doses of hapten [2,4-dinitrophenyl (DNP)]-coupled type 3 pneumococcal polysaccharide (DNP-lys2.5-S3) totally abolished the anti-DNP rosette-forming cell (RFC) response to primary immunization with DNP-hemocyanin in mice, while lightly substituted antigen (DNP-lys0.6-S3) had little effect. Both antigens suppressed secondary anti-DNP RFC responses to DNP-KLH. Limiting doses of DNP-lys-S3 preferentially suppressed antibody-secreting cell levels, and had less effect on RFC. DNP-lys2.5-S3 was 500--1000-fold more potent in \"blockading\" primary RFC in vitro than DNP-lys0.6-S3, whereas both antigens were equally effective in blocking secondary RFC. These results suggest that the sensitivity of primed B lymphocytes to inactivation by DNP-lys-S3 is related to their high avidity for antigen. Furthermore, this appears to be largely due to a high density of immunoglobulin receptors on primed cells since the affinities of primary and secondary RFC for monovalent hapten were indistinguishable. Treatment of primarily immunized mice with DNP-lys2.5-S3 2 h before assay abolished 90% of RFC. Therefore, the reduction in RFC levels in tolerant mice may be due to cellular blockade by persisting tolerogen. However, it seems unlikely that simple blockade of antigen-reactive cells is the sole mechanism operative in this system.", "contents": "B cell tolerance induced by polymeric antigens. II. Effects of tolerance on hapten-binding lymphocyte levels in primary and secondary antibody responses. Tolerogenic doses of hapten [2,4-dinitrophenyl (DNP)]-coupled type 3 pneumococcal polysaccharide (DNP-lys2.5-S3) totally abolished the anti-DNP rosette-forming cell (RFC) response to primary immunization with DNP-hemocyanin in mice, while lightly substituted antigen (DNP-lys0.6-S3) had little effect. Both antigens suppressed secondary anti-DNP RFC responses to DNP-KLH. Limiting doses of DNP-lys-S3 preferentially suppressed antibody-secreting cell levels, and had less effect on RFC. DNP-lys2.5-S3 was 500--1000-fold more potent in \"blockading\" primary RFC in vitro than DNP-lys0.6-S3, whereas both antigens were equally effective in blocking secondary RFC. These results suggest that the sensitivity of primed B lymphocytes to inactivation by DNP-lys-S3 is related to their high avidity for antigen. Furthermore, this appears to be largely due to a high density of immunoglobulin receptors on primed cells since the affinities of primary and secondary RFC for monovalent hapten were indistinguishable. Treatment of primarily immunized mice with DNP-lys2.5-S3 2 h before assay abolished 90% of RFC. Therefore, the reduction in RFC levels in tolerant mice may be due to cellular blockade by persisting tolerogen. However, it seems unlikely that simple blockade of antigen-reactive cells is the sole mechanism operative in this system."}
{"id": "PMID:10169", "title": "Recruitment of effector lymphocytes by initiator lymphocytes. In vivo migration of in vitro sensitized initiator T lymphocytes.", "content": "We previously found that mouse T lymphocytes sensitized in vitro against allo- or syngeneic fibroblasts, upon injection into syngeneic recipients, do not themselves differentiate into effector cells, but recruit effector T lymphocytes within the draining lymph nodes. As a result of sensitization, these initiator lymphocytes acquire a trypsin-sensitive membrane property which is necessary for recruitment. We now report studies on the in vivo migratory behavior of initiator lymphocytes following sensitization. We injected 51Cr-labeled initiator lymphocytes into recipient footpads and found significantly increased migration of sensitized cells to the draining popliteal lymph node (PLN) during the first day. By amputation of the foot at various times, we showed that migration during the first 12-24 hours was critical for subsequent recruitment. Trypsin treatment of initiator lymphocytes abolished this accelerated migration. Lymphocytes triggered nonspecifically by Con A migrated to the PLN like antigen-sensitized cells. We also compared the migration of injected lymphocytes from the footpad to the PLN in graft-versus-host and host-versus-graft reactions, and found these reactions to differ both from each other and from recruitment in terms of lymphocyte migration. These findings are discussed in terms of the physiology of the cell-mediated immune response and the notion of peripheral sensitization.", "contents": "Recruitment of effector lymphocytes by initiator lymphocytes. In vivo migration of in vitro sensitized initiator T lymphocytes. We previously found that mouse T lymphocytes sensitized in vitro against allo- or syngeneic fibroblasts, upon injection into syngeneic recipients, do not themselves differentiate into effector cells, but recruit effector T lymphocytes within the draining lymph nodes. As a result of sensitization, these initiator lymphocytes acquire a trypsin-sensitive membrane property which is necessary for recruitment. We now report studies on the in vivo migratory behavior of initiator lymphocytes following sensitization. We injected 51Cr-labeled initiator lymphocytes into recipient footpads and found significantly increased migration of sensitized cells to the draining popliteal lymph node (PLN) during the first day. By amputation of the foot at various times, we showed that migration during the first 12-24 hours was critical for subsequent recruitment. Trypsin treatment of initiator lymphocytes abolished this accelerated migration. Lymphocytes triggered nonspecifically by Con A migrated to the PLN like antigen-sensitized cells. We also compared the migration of injected lymphocytes from the footpad to the PLN in graft-versus-host and host-versus-graft reactions, and found these reactions to differ both from each other and from recruitment in terms of lymphocyte migration. These findings are discussed in terms of the physiology of the cell-mediated immune response and the notion of peripheral sensitization."}
{"id": "PMID:10170", "title": "Immunologic induction of reticulum cell sarcoma: donor-type lymphomas in the graft-versus-host model.", "content": "The aim of this study was to investigate malignant lymphomas of donor origin induced in F1 mice undergoing a chronic graft-versus-host reaction (GVHR) after injection of parental strain spleen cells. A total of 3 X 10(8) or 4 X 10(8) C57BL/10 spleen cells were administered to 7-8-week-old H-2 incompatible (C57BL/10 X HTG)F1 hybrids either as single or fractionated i.p. injections. Recipients were killed at intervals ranging from 1 month to 1 year after the first injection and their lymphoid cells typed for host-derived and donor-derived histocompatibility antigens. In 49% of the 88 GVH F1 mice, cells failed to be killed by a hyperimmune serum against HTG (H-2g) but reacted normally with antisera to C57BL/10 (H-2b) and, in the 9 cases tested, to theta-C3H. The conclusion that the lymphoid cells of these mice were derived from donor cells was supported by the finding that these animals lacked immunoglobulins bearing host-derived Iga allotype in their serum. Forty-three percent of the GVH F1 mice developed reticulum cell sarcomas (RCS), 32% revealed hyperplastic lymphoreticular tissue, and 25% showed no grossly abnormal changes. Mice with donor-type lymphoid tissues were found in all three groups; 50% of the 38 RCS detected were donor-type neoplasms. The induction of donor-type RCS during the GVHR strengthens the concept of lymphomagenesis through persistent stimulation with antigen(s).", "contents": "Immunologic induction of reticulum cell sarcoma: donor-type lymphomas in the graft-versus-host model. The aim of this study was to investigate malignant lymphomas of donor origin induced in F1 mice undergoing a chronic graft-versus-host reaction (GVHR) after injection of parental strain spleen cells. A total of 3 X 10(8) or 4 X 10(8) C57BL/10 spleen cells were administered to 7-8-week-old H-2 incompatible (C57BL/10 X HTG)F1 hybrids either as single or fractionated i.p. injections. Recipients were killed at intervals ranging from 1 month to 1 year after the first injection and their lymphoid cells typed for host-derived and donor-derived histocompatibility antigens. In 49% of the 88 GVH F1 mice, cells failed to be killed by a hyperimmune serum against HTG (H-2g) but reacted normally with antisera to C57BL/10 (H-2b) and, in the 9 cases tested, to theta-C3H. The conclusion that the lymphoid cells of these mice were derived from donor cells was supported by the finding that these animals lacked immunoglobulins bearing host-derived Iga allotype in their serum. Forty-three percent of the GVH F1 mice developed reticulum cell sarcomas (RCS), 32% revealed hyperplastic lymphoreticular tissue, and 25% showed no grossly abnormal changes. Mice with donor-type lymphoid tissues were found in all three groups; 50% of the 38 RCS detected were donor-type neoplasms. The induction of donor-type RCS during the GVHR strengthens the concept of lymphomagenesis through persistent stimulation with antigen(s)."}
{"id": "PMID:10171", "title": "Graft-versus-host reaction induced by Peyer's patches.", "content": "Parental Peyer's patches were implanted into the anterior hepatic lobe of F1 hybrid rats. Using conventional histological techniques, phenomena typical of a graft-versus-host reaction were observed, such as paravascular lymphoid infiltration in the liver, cellular depletion of the thymus-dependent areas of spleen, and diffuse reticuloendothelial cell proliferation in various lymphoid tissues. Based on these findings and other observations it is concluded that a thymus-dependent cell population is present in the Peyer's patches.", "contents": "Graft-versus-host reaction induced by Peyer's patches. Parental Peyer's patches were implanted into the anterior hepatic lobe of F1 hybrid rats. Using conventional histological techniques, phenomena typical of a graft-versus-host reaction were observed, such as paravascular lymphoid infiltration in the liver, cellular depletion of the thymus-dependent areas of spleen, and diffuse reticuloendothelial cell proliferation in various lymphoid tissues. Based on these findings and other observations it is concluded that a thymus-dependent cell population is present in the Peyer's patches."}
{"id": "PMID:10172", "title": "Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. I. Studies with 2,4-dinitrophenyl conjugates in vitro.", "content": "The effect of different degrees of conjugation of levan, dextran, pneumococcal polysaccharide SIII and the copolymer of D-glutamic acid and D-lysine with the 2,4-dinitrophenyl determinant (DNP) on the immunogenic and tolerogenic capacity of its haptenic conjugates was investigated in vitro. A strikingly uniform effect of hapten conjugation was observed despite the marked difference in the mol. wt. and structure (branched or linear) of the carrier molecules. Regarding the anti-DNP response, low density conjugates were immunogenic but not tolerogenic (even at high doses), higher conjugates were both, depending on concentration, while very high density conjugates were only tolerogenic. These results confirm and extend earlier findings made with DNP conjugates of polymeric flagellin and indicate the probable generality of this principle. Together with parallel in vivo studies (Eur. J. Immunol. 1975. 5:541), they reaffirm the importance of epitope density in the discrimination between immunity and tolerance.", "contents": "Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. I. Studies with 2,4-dinitrophenyl conjugates in vitro. The effect of different degrees of conjugation of levan, dextran, pneumococcal polysaccharide SIII and the copolymer of D-glutamic acid and D-lysine with the 2,4-dinitrophenyl determinant (DNP) on the immunogenic and tolerogenic capacity of its haptenic conjugates was investigated in vitro. A strikingly uniform effect of hapten conjugation was observed despite the marked difference in the mol. wt. and structure (branched or linear) of the carrier molecules. Regarding the anti-DNP response, low density conjugates were immunogenic but not tolerogenic (even at high doses), higher conjugates were both, depending on concentration, while very high density conjugates were only tolerogenic. These results confirm and extend earlier findings made with DNP conjugates of polymeric flagellin and indicate the probable generality of this principle. Together with parallel in vivo studies (Eur. J. Immunol. 1975. 5:541), they reaffirm the importance of epitope density in the discrimination between immunity and tolerance."}
{"id": "PMID:10173", "title": "Effect of antipsychotic drugs on the firing of dorsal raphe cells. I. Role of adrenergic system.", "content": "The activity of serotonergic (5HT) neurons in the dorsal raphe nucleus was inhibited by the i.v. administration of certain antipsychotic drugs (methiothepin, clozapine and thioridazine). However, other antipsychotic agents (chlorpromazine, haloperidol and pimozide) did not inhibit raphe cell firing. The inhibitory potency of these drugs on raphe activity correlates with reported central noradrenergic blocking efficacy. An alpha-adrenergic blocking agent, piperoxane, but not the beta-blocking agents, propranolol and MJ 1999, inhibited raphe activity when administered systemically. All of these drugs appear to act indirectly since they (and NE) have relatively weak or variable effects when applied microiontophoretically to raphe neurons. The depressant effects of certain antipsychotic drugs and piperoxane on 5HT neurons appears to be mediated by a cnetral adrenergic system since (1) the depression could be reversed by the catecholamine releasing agents 1- and d-amphetamine; (2) the depression could be abolished by destruction of adrenergic pathways in the CNS by chemical, mechanical, or electrothermic lesions. While a precise localization has not yet been obtained, the data suggest that these drug effects may be mediated by an adrenergic pathway ascending from the lower brainstem.", "contents": "Effect of antipsychotic drugs on the firing of dorsal raphe cells. I. Role of adrenergic system. The activity of serotonergic (5HT) neurons in the dorsal raphe nucleus was inhibited by the i.v. administration of certain antipsychotic drugs (methiothepin, clozapine and thioridazine). However, other antipsychotic agents (chlorpromazine, haloperidol and pimozide) did not inhibit raphe cell firing. The inhibitory potency of these drugs on raphe activity correlates with reported central noradrenergic blocking efficacy. An alpha-adrenergic blocking agent, piperoxane, but not the beta-blocking agents, propranolol and MJ 1999, inhibited raphe activity when administered systemically. All of these drugs appear to act indirectly since they (and NE) have relatively weak or variable effects when applied microiontophoretically to raphe neurons. The depressant effects of certain antipsychotic drugs and piperoxane on 5HT neurons appears to be mediated by a cnetral adrenergic system since (1) the depression could be reversed by the catecholamine releasing agents 1- and d-amphetamine; (2) the depression could be abolished by destruction of adrenergic pathways in the CNS by chemical, mechanical, or electrothermic lesions. While a precise localization has not yet been obtained, the data suggest that these drug effects may be mediated by an adrenergic pathway ascending from the lower brainstem."}
{"id": "PMID:10174", "title": "Effect of antipsychotic drugs on the firing of dorsal raphe cells. II. Reversal by picrotoxin.", "content": "As reported in the preceding study, the ability of certain antipsychotic and adrenolytic agents to inhibit the spontaneous firing of serotonergic 5HT neurons in the dorsal raphe nucleus appeared to be related to adrenergic blocking efficacy. However, the interaction between adrenergic and serotonergic systems was apparently indirect. In this phase of the study we investigated the hypothesis that another transmitter system could mediate this interaction. We examined the effects of two inhibitory amino acid transmitters (GABA and glycine) for possible effects on dorsal raphe cell firing using single cell recording and microiontophoretic techniques. In addition, the ability of the GABA antagonist, picrotoxin and the glycine antagonist, strychnine to reverse the effects of the antipsychotic and alpha-blocking drugs on dorsal raphe firing was tested. Both GABA and glycine were found to inhibit raphe cell firing selectively, allowing for a possible neurotransmitter function for these amino acids within the dorsal raphe nucleus. However, picrotoxin but not strychnine was found to reverse the effects of the antipsychotic and alpha-blocking drugs on raphe firing. Based on these results, we propose that the adrenergic input may influence 5HT neurons indirectly via a GABAergic interneuron or interposed GABA neuron.", "contents": "Effect of antipsychotic drugs on the firing of dorsal raphe cells. II. Reversal by picrotoxin. As reported in the preceding study, the ability of certain antipsychotic and adrenolytic agents to inhibit the spontaneous firing of serotonergic 5HT neurons in the dorsal raphe nucleus appeared to be related to adrenergic blocking efficacy. However, the interaction between adrenergic and serotonergic systems was apparently indirect. In this phase of the study we investigated the hypothesis that another transmitter system could mediate this interaction. We examined the effects of two inhibitory amino acid transmitters (GABA and glycine) for possible effects on dorsal raphe cell firing using single cell recording and microiontophoretic techniques. In addition, the ability of the GABA antagonist, picrotoxin and the glycine antagonist, strychnine to reverse the effects of the antipsychotic and alpha-blocking drugs on dorsal raphe firing was tested. Both GABA and glycine were found to inhibit raphe cell firing selectively, allowing for a possible neurotransmitter function for these amino acids within the dorsal raphe nucleus. However, picrotoxin but not strychnine was found to reverse the effects of the antipsychotic and alpha-blocking drugs on raphe firing. Based on these results, we propose that the adrenergic input may influence 5HT neurons indirectly via a GABAergic interneuron or interposed GABA neuron."}
{"id": "PMID:10176", "title": "Regulation of enzymes of ethanol metabolism in yeast (Rhodotorula gracilis).", "content": "The three enzymes of ethanol metabolism alcohol dehydrogenase, aldehyde dehydrogenase and acetyl-CoA synthetase in the obligate aerobic yeast Rhodotorula gracilis are repressed by glucose and induced by C2 metabolic fuels with a regulatory pattern indicating a correlation in the control mechanisms. To try an identification of the molecular signals involved in the transmission of the inducing stimulus, experiments were carried out by blocking with 2 mM pyrazole the ethanol acetaldehyde metabolic step. Results indicate that ethanol is not specifically required as a molecular signal for induction.", "contents": "Regulation of enzymes of ethanol metabolism in yeast (Rhodotorula gracilis). The three enzymes of ethanol metabolism alcohol dehydrogenase, aldehyde dehydrogenase and acetyl-CoA synthetase in the obligate aerobic yeast Rhodotorula gracilis are repressed by glucose and induced by C2 metabolic fuels with a regulatory pattern indicating a correlation in the control mechanisms. To try an identification of the molecular signals involved in the transmission of the inducing stimulus, experiments were carried out by blocking with 2 mM pyrazole the ethanol acetaldehyde metabolic step. Results indicate that ethanol is not specifically required as a molecular signal for induction."}
{"id": "PMID:10178", "title": "Lipoperoxidation rates and drug-oxidizing enzyme activities in the liver and placenta of some mammal species during the perinatal period.", "content": "Lipoperoxidation and drug-metabolizing enzymes were measured in livers and placentas of different mammal species during the perinatal perios. In placentas and fetal livers of rat, rabbit and guinea-pig, cofactor-supported lipoperoxidation was negligible, as were the activities of drug-oxidizing enzymes. Human fetal liver contained an intact drug-oxidizing electron transport chain, and lipoperoxidation activity was accordingly abserved. It is suggested that lesions mediated by lipoperoxidation may be possible in human fetus, but they are less probable in animal fetuses.", "contents": "Lipoperoxidation rates and drug-oxidizing enzyme activities in the liver and placenta of some mammal species during the perinatal period. Lipoperoxidation and drug-metabolizing enzymes were measured in livers and placentas of different mammal species during the perinatal perios. In placentas and fetal livers of rat, rabbit and guinea-pig, cofactor-supported lipoperoxidation was negligible, as were the activities of drug-oxidizing enzymes. Human fetal liver contained an intact drug-oxidizing electron transport chain, and lipoperoxidation activity was accordingly abserved. It is suggested that lesions mediated by lipoperoxidation may be possible in human fetus, but they are less probable in animal fetuses."}
{"id": "PMID:10179", "title": "Similarities between sodium channels in excitable membranes and in epithelia.", "content": "The inhibitory effects of the pyrazine derivative, amiloride, on sodium transport in an amphibian epithelium has been studied as a function of pH. It is concluded that the charged (guanidinium) group interacts with a negatively charged acid grouping in the membrane. Similarities between sodium channels in excitable membranes and epithelia are highlighted.", "contents": "Similarities between sodium channels in excitable membranes and in epithelia. The inhibitory effects of the pyrazine derivative, amiloride, on sodium transport in an amphibian epithelium has been studied as a function of pH. It is concluded that the charged (guanidinium) group interacts with a negatively charged acid grouping in the membrane. Similarities between sodium channels in excitable membranes and epithelia are highlighted."}
{"id": "PMID:10180", "title": "Different types of synaptic vesicles in axons of the retractor penis muscle of the bull.", "content": "Three types of axon profiles were observed in the smooth muscle of the retractor penis and the penile artery of the bull: 1. profiles containing small granular vesicles, presumably representing adrenergic axons; 2. profiles containing small agranular vesicles, presumably representing cholinergic axons; 3. profiles containing numerous large and small granular vesicles. The third type of profile was not found in the vas deferens or the metatarsal artery. It is therefore possible that this type of profile represents the non-adrenergic, non-cholinergic inhibitory nerves, the presence of which has previously been pharmacologically indicated in these tissues.", "contents": "Different types of synaptic vesicles in axons of the retractor penis muscle of the bull. Three types of axon profiles were observed in the smooth muscle of the retractor penis and the penile artery of the bull: 1. profiles containing small granular vesicles, presumably representing adrenergic axons; 2. profiles containing small agranular vesicles, presumably representing cholinergic axons; 3. profiles containing numerous large and small granular vesicles. The third type of profile was not found in the vas deferens or the metatarsal artery. It is therefore possible that this type of profile represents the non-adrenergic, non-cholinergic inhibitory nerves, the presence of which has previously been pharmacologically indicated in these tissues."}
{"id": "PMID:10215", "title": "Properties of renin granules isolated from rat kidney.", "content": "Renin granules from rat kidney prepared at 25 degrees C show greater stability at 25 degrees C than at 0 degrees C when incubated in ionic medium. The sum of the renin in the supernatant fluid plus that in the pellet was the same at 25 degrees C as at 0 degrees C, thus ruling out the possibility that the extra release at 0 degrees C merely represented greater stability of free renin at 0 degrees C. In common with other secretory granules, renin granules were most stable at pH 6.0 and were osmotically sensitive. In contrast to neurosecretory and chromaffin granules, renin granules were stabilized by Mg-ATP in ionic medium. This result is similar to studies by others on lysosomes. It is concluded that the renin granules membrane shares many of the properties of other granule membranes. Some of these properties (temperature and pH lability) will have to be considered in the design of future experiments on renin storage and release.", "contents": "Properties of renin granules isolated from rat kidney. Renin granules from rat kidney prepared at 25 degrees C show greater stability at 25 degrees C than at 0 degrees C when incubated in ionic medium. The sum of the renin in the supernatant fluid plus that in the pellet was the same at 25 degrees C as at 0 degrees C, thus ruling out the possibility that the extra release at 0 degrees C merely represented greater stability of free renin at 0 degrees C. In common with other secretory granules, renin granules were most stable at pH 6.0 and were osmotically sensitive. In contrast to neurosecretory and chromaffin granules, renin granules were stabilized by Mg-ATP in ionic medium. This result is similar to studies by others on lysosomes. It is concluded that the renin granules membrane shares many of the properties of other granule membranes. Some of these properties (temperature and pH lability) will have to be considered in the design of future experiments on renin storage and release."}
{"id": "PMID:10217", "title": "A sensitive method for measuring haemoglobin in gastric contents.", "content": "A sensitive method for measuring haemoglobin in gastric contents using the rate of change of optical density of a mixture of orthotolidine and hydrogen peroxide in the presence of haemoglobin, is described. The method can measure the blood normally lost in 10 min from the gastric mucosa.", "contents": "A sensitive method for measuring haemoglobin in gastric contents. A sensitive method for measuring haemoglobin in gastric contents using the rate of change of optical density of a mixture of orthotolidine and hydrogen peroxide in the presence of haemoglobin, is described. The method can measure the blood normally lost in 10 min from the gastric mucosa."}
{"id": "PMID:10218", "title": "[Blood gas analysis and acid-base balance in acute myocardial infarction. Personal observations (author's transl)].", "content": "Arterial pH, pO2 and pCO2 were analysed with Astup's micromethod on one hundred and three acute myocardial infarctions (A.M.I.) without metabolic, pulmonary and renal diseases. Following the clinical picute, the patients were divided into five groups and results were clinically and statistically evaluated (mean, standard deviation, Student's test \"t\", correlation coefficient \"r\" between pO2 and pulmonary arterial diastolic pressure): --Ist group (A.M.I. without complications): only mild hypoxemia; --IInd group (A.M.I. with slight left ventricular failure): more remarkable hypoxemia and hypocapnia, often with respiratory alkalosis; --IIIrd group (A.M.I. complicated by acute pulmonary oedema): mixed acidosis and severe hypoxemia; --IVth group (A.M.I. complicated by shock): prevailing metabolic acidosis and severe hypoxemia. Acidosis shows good correlations with the clinical picture; --Vth group (A.M.I. with serious arrhythmias): mixed and profound acidosis and important hypoxemia during ventricular fibrillation and cardiac arrest. In twenty patients hypoxemia and arterial pulmonary diastolic pressure showed a significant correlation.", "contents": "[Blood gas analysis and acid-base balance in acute myocardial infarction. Personal observations (author's transl)]. Arterial pH, pO2 and pCO2 were analysed with Astup's micromethod on one hundred and three acute myocardial infarctions (A.M.I.) without metabolic, pulmonary and renal diseases. Following the clinical picute, the patients were divided into five groups and results were clinically and statistically evaluated (mean, standard deviation, Student's test \"t\", correlation coefficient \"r\" between pO2 and pulmonary arterial diastolic pressure): --Ist group (A.M.I. without complications): only mild hypoxemia; --IInd group (A.M.I. with slight left ventricular failure): more remarkable hypoxemia and hypocapnia, often with respiratory alkalosis; --IIIrd group (A.M.I. complicated by acute pulmonary oedema): mixed acidosis and severe hypoxemia; --IVth group (A.M.I. complicated by shock): prevailing metabolic acidosis and severe hypoxemia. Acidosis shows good correlations with the clinical picture; --Vth group (A.M.I. with serious arrhythmias): mixed and profound acidosis and important hypoxemia during ventricular fibrillation and cardiac arrest. In twenty patients hypoxemia and arterial pulmonary diastolic pressure showed a significant correlation."}
{"id": "PMID:10219", "title": "Salycylamide glucuronide formation in liver disease and its change by drugs.", "content": "Salicylamide glucuronide (SAMG) in 0-6 and 6-12 hours-urine specimens was determined after oral administration of salicylamide in 7 normal volunteers (NV), in 51 cases of various liver diseases and hyperbilirubinemias, and in 19 cases after drug administration, to predict the in vivo drug metabolism in man and its change by drugs. Maximal glucuronide formation was obtained by 1.0 g of salicylamide administered to NV; thus, this dosage was used in the present study. SAMG as percent of total salicylamide, the percent of SAMG, from 0-6 hours-urine specimens was high and constant in NV (71.3 +/- 8.3 (Mean +/- S.D.)). 0-0.08% of the total salicylamide was confirmed as free salicylamide in 0-12 hours-urine specimens of NV. The percent of SAMG of 0-6 hours-urine specimens was 57.2 +/- 8.6 in acute hepatitis, 66.6 +/- 10.9 in chronic hepatitis, and 48.6 +/- 10.7 in liver cirrhosis (mean +/- S.D.). Free salicylamide increased slightly in liver diseases. Serum bilirubin levels tended to be inversely correlated with the percent of SAMG. In most cases of Gilbert's syndrome, the percent of SAMG remained at a normal level. The percent of SAMG in cases with unconjugated hyperbilirubinemias of other geneses were almost within normal limits. Bucolome and phenobarbital increased the percent of SAMG in patients with various liver diseases. After rifampicin or phenytoin administration, the percent of SAMG of the patients with lung tuberculosis or epilepsy did not surpass that of NV.", "contents": "Salycylamide glucuronide formation in liver disease and its change by drugs. Salicylamide glucuronide (SAMG) in 0-6 and 6-12 hours-urine specimens was determined after oral administration of salicylamide in 7 normal volunteers (NV), in 51 cases of various liver diseases and hyperbilirubinemias, and in 19 cases after drug administration, to predict the in vivo drug metabolism in man and its change by drugs. Maximal glucuronide formation was obtained by 1.0 g of salicylamide administered to NV; thus, this dosage was used in the present study. SAMG as percent of total salicylamide, the percent of SAMG, from 0-6 hours-urine specimens was high and constant in NV (71.3 +/- 8.3 (Mean +/- S.D.)). 0-0.08% of the total salicylamide was confirmed as free salicylamide in 0-12 hours-urine specimens of NV. The percent of SAMG of 0-6 hours-urine specimens was 57.2 +/- 8.6 in acute hepatitis, 66.6 +/- 10.9 in chronic hepatitis, and 48.6 +/- 10.7 in liver cirrhosis (mean +/- S.D.). Free salicylamide increased slightly in liver diseases. Serum bilirubin levels tended to be inversely correlated with the percent of SAMG. In most cases of Gilbert's syndrome, the percent of SAMG remained at a normal level. The percent of SAMG in cases with unconjugated hyperbilirubinemias of other geneses were almost within normal limits. Bucolome and phenobarbital increased the percent of SAMG in patients with various liver diseases. After rifampicin or phenytoin administration, the percent of SAMG of the patients with lung tuberculosis or epilepsy did not surpass that of NV."}
{"id": "PMID:10220", "title": "Influence of drugs and chemicals upon hepatic enzymes and proteins. II. The effects of various barbiturates on the induction and reduction of hepatic cytoplasmic organic anion-binding proteins.", "content": "The effects of seven barbiturates (phenobarbital, three N-phenylbarbiturates and three N-cyclohexylbarbiturates) on the hepatic cytoplasmic organic anion-binding proteins, Y and Z, were investigated in an attempt to observe the structure-activity relationship of baributrates to induction and reduction of these two proteins. Sulfobromophthalein (BSP) was fully bound by the Y and Z proteins at ten minutes of mixing with the 10,5000 X g supernate. In low concentrations of BSP, saturation of binding of BSP by the Z protein was very low, and with increasing concentration, BSP-binding by the Z protein increased rapidly. The Y protein bound BSP sufficiently even in low concentrations of the dye. BSP-binding capacity of the Yprotein was increased by phenobarbital, phetharbital and bucolome, and decreased by one of the N-phenylbarbiturates. BSP-binding capacity of the Zprotein tended to be decreased by phenobarbital and phetharbital, but to be increased by bucolome. The other N-phenyl- and N-cyclohexylbarbiturates had no effect on the binding capacities of the two proteins. From these results it was concluded that the regulation by the barbiturates of cytoplasmic proteins is different from that of the microsomal enzymes, and that both type and structural relation are important in the induction and reduction of the Y and Z proteins.", "contents": "Influence of drugs and chemicals upon hepatic enzymes and proteins. II. The effects of various barbiturates on the induction and reduction of hepatic cytoplasmic organic anion-binding proteins. The effects of seven barbiturates (phenobarbital, three N-phenylbarbiturates and three N-cyclohexylbarbiturates) on the hepatic cytoplasmic organic anion-binding proteins, Y and Z, were investigated in an attempt to observe the structure-activity relationship of baributrates to induction and reduction of these two proteins. Sulfobromophthalein (BSP) was fully bound by the Y and Z proteins at ten minutes of mixing with the 10,5000 X g supernate. In low concentrations of BSP, saturation of binding of BSP by the Z protein was very low, and with increasing concentration, BSP-binding by the Z protein increased rapidly. The Y protein bound BSP sufficiently even in low concentrations of the dye. BSP-binding capacity of the Yprotein was increased by phenobarbital, phetharbital and bucolome, and decreased by one of the N-phenylbarbiturates. BSP-binding capacity of the Zprotein tended to be decreased by phenobarbital and phetharbital, but to be increased by bucolome. The other N-phenyl- and N-cyclohexylbarbiturates had no effect on the binding capacities of the two proteins. From these results it was concluded that the regulation by the barbiturates of cytoplasmic proteins is different from that of the microsomal enzymes, and that both type and structural relation are important in the induction and reduction of the Y and Z proteins."}
{"id": "PMID:10221", "title": "The estimation of gastric secretory capacity by the telemetering method of pH-sensitive radiocapsule.", "content": "Using a pH-sensitive radiotelemetering capsule with antimony electrode or glass electrode, the capacity of the gastric acid secretion was determined according to a modified Satveny's method on four healthy controls and 19 patients with peptic ulcer, and it was compared with that from the usual aspiration method. As to the basal condition, acid output couldn't be measured by the telemetering method in most cases because of high pH value in the stomach. There was no definite relation between two methods. On the other hand, acid output from the telemetering after stimulation of AOC-tetragastrin (4 gamma/kg, s.c.) showed a good reproducibility and good correlation with that from the aspiration method (r = +0.86). And the difference between two methods could be explained from the fact that some volume of secreted acid escaped into the duodenum before being neutralized by potassium bicarbonate, and that some of gastric juice remained not aspirated in the stomach.", "contents": "The estimation of gastric secretory capacity by the telemetering method of pH-sensitive radiocapsule. Using a pH-sensitive radiotelemetering capsule with antimony electrode or glass electrode, the capacity of the gastric acid secretion was determined according to a modified Satveny's method on four healthy controls and 19 patients with peptic ulcer, and it was compared with that from the usual aspiration method. As to the basal condition, acid output couldn't be measured by the telemetering method in most cases because of high pH value in the stomach. There was no definite relation between two methods. On the other hand, acid output from the telemetering after stimulation of AOC-tetragastrin (4 gamma/kg, s.c.) showed a good reproducibility and good correlation with that from the aspiration method (r = +0.86). And the difference between two methods could be explained from the fact that some volume of secreted acid escaped into the duodenum before being neutralized by potassium bicarbonate, and that some of gastric juice remained not aspirated in the stomach."}
{"id": "PMID:10222", "title": "Effect of salts on the kinetic parameters and thermal stability of bovine brain acid phosphatase.", "content": "Bovine brain acid phosphatase is inhibited, at any pH, by an increase in ionic strength. The rate decrease is associated at pH 5, with a marked decrease in Km and, at pH 8, with a noticeable decrease in Vm. The rate of thermal inactivation of the enzyme is unaffected by increasing ionic strength up to 300 mM. These results are discussed in terms of interactions at the active site of the enzyme.", "contents": "Effect of salts on the kinetic parameters and thermal stability of bovine brain acid phosphatase. Bovine brain acid phosphatase is inhibited, at any pH, by an increase in ionic strength. The rate decrease is associated at pH 5, with a marked decrease in Km and, at pH 8, with a noticeable decrease in Vm. The rate of thermal inactivation of the enzyme is unaffected by increasing ionic strength up to 300 mM. These results are discussed in terms of interactions at the active site of the enzyme."}
{"id": "PMID:10223", "title": "A pharmacological study of the angiotensin receptor and tachyphylaxis in smooth muscle.", "content": "The interaction of angiotensin with its receptor has been studied on the basis of the tachyphylaxis shown by the rat uterus towards angiotensin II when pH and Ca2+ concentration are below physiological levels. 14C-Angiotensin binding and 45Ca2+-uptake investigations suggest tachyphylaxis to be due to increased binding at low pH and Ca2+ concentration. Studies with alkylating (affinity labeled) angiotensin derivatives containing the N-mustard chlorambucil suggest a \"Charni\u00e8re type\" inhibition at the Ca-binding site of receptor and an irreversible inhibition at an anionic site. Angiotensin inhibitors containing chlorambucil do not alkylate tissue but are competitive inhibitors suggesting that the aromatic side chain in angiotensin may induce conformational changes in the receptor. The results obtained lead to a logical model for the angiotensin receptor allowing for normal activation by the hormone as well as for production of tachyphylaxis.", "contents": "A pharmacological study of the angiotensin receptor and tachyphylaxis in smooth muscle. The interaction of angiotensin with its receptor has been studied on the basis of the tachyphylaxis shown by the rat uterus towards angiotensin II when pH and Ca2+ concentration are below physiological levels. 14C-Angiotensin binding and 45Ca2+-uptake investigations suggest tachyphylaxis to be due to increased binding at low pH and Ca2+ concentration. Studies with alkylating (affinity labeled) angiotensin derivatives containing the N-mustard chlorambucil suggest a \"Charni\u00e8re type\" inhibition at the Ca-binding site of receptor and an irreversible inhibition at an anionic site. Angiotensin inhibitors containing chlorambucil do not alkylate tissue but are competitive inhibitors suggesting that the aromatic side chain in angiotensin may induce conformational changes in the receptor. The results obtained lead to a logical model for the angiotensin receptor allowing for normal activation by the hormone as well as for production of tachyphylaxis."}
{"id": "PMID:10224", "title": "5-Hydroxytryptamine and narcotic-analgesics interactions in the intestine.", "content": "The effects of 5-hydroxytriptamine (5-HT), 5-HT blocking agents, morphine, narcotic-antagonists and ganglionic blocking agents were tested in the dog intestine by close intra-arterial injection. Morphine, as 5-HT, induced an immediate increase in the intestinal tonus followed by phasic contractions. When 5-HT was injected immediately after cessation of morphine induced phasic contractions, a significant potentiation of the 5-HT induced intestinal contraction could be observed. The potentiation could be demonstrated for other narcotic-analgesics like dextromoramide and it is specific for 5-HT. 5-HT blocking agents like LSD, BOL, and cyproheptadine did not block either 5-HT or morphine. However, bufotenidine, a neural tryptaminergic blocking agent, blocked the effects of both 5-HT and morphine. The effects of 5-HT and morphine upon intestinal motility were also diminished by ganglionic depolarizing agents such as nicotine and DMPP. This effect could, however, be prevented by the pretreatment with hexamethonium. These results seem to confirm the hypothesis of a 5-HT mediator role in the intestinal contractile effect induced by the narcotic-analgesics. On the other hand, narcotic-antagonists such as nalorphine and cyclazocine, not only lacked the 5-HT potentiation effect but also prevented the 5-HT potentiation induced by morphine. Cyclazocine also showed a long lasting 5-HT blocking effect. These results seem to show that the 5-HT potentiating effect of morphine in vivo is very specific and characteristic of the narcotics and thus could be implicated in some of their central effects.", "contents": "5-Hydroxytryptamine and narcotic-analgesics interactions in the intestine. The effects of 5-hydroxytriptamine (5-HT), 5-HT blocking agents, morphine, narcotic-antagonists and ganglionic blocking agents were tested in the dog intestine by close intra-arterial injection. Morphine, as 5-HT, induced an immediate increase in the intestinal tonus followed by phasic contractions. When 5-HT was injected immediately after cessation of morphine induced phasic contractions, a significant potentiation of the 5-HT induced intestinal contraction could be observed. The potentiation could be demonstrated for other narcotic-analgesics like dextromoramide and it is specific for 5-HT. 5-HT blocking agents like LSD, BOL, and cyproheptadine did not block either 5-HT or morphine. However, bufotenidine, a neural tryptaminergic blocking agent, blocked the effects of both 5-HT and morphine. The effects of 5-HT and morphine upon intestinal motility were also diminished by ganglionic depolarizing agents such as nicotine and DMPP. This effect could, however, be prevented by the pretreatment with hexamethonium. These results seem to confirm the hypothesis of a 5-HT mediator role in the intestinal contractile effect induced by the narcotic-analgesics. On the other hand, narcotic-antagonists such as nalorphine and cyclazocine, not only lacked the 5-HT potentiation effect but also prevented the 5-HT potentiation induced by morphine. Cyclazocine also showed a long lasting 5-HT blocking effect. These results seem to show that the 5-HT potentiating effect of morphine in vivo is very specific and characteristic of the narcotics and thus could be implicated in some of their central effects."}
{"id": "PMID:10225", "title": "The effect of cold storage on the sensitivity to alpha and beta agonists in the isolated rabbit kidney.", "content": "Rabbit kidneys were perfused at 25 degrees C, and the effect of alpha and beta agonists was studied, before and after 24 hr of cold storage. Vascular and in vitro functional parameters were evaluated. We concluded that cold storage impairs partially the vascular alpha receptor. We could not find beta receptors under these conditions. An electron microscope analysis of these kidneys has shown some degree of autolysis of the tubular cells and good preservation of the vascular smooth muscle cells and membranes. These results are very important for kidney preservation before transplantation.", "contents": "The effect of cold storage on the sensitivity to alpha and beta agonists in the isolated rabbit kidney. Rabbit kidneys were perfused at 25 degrees C, and the effect of alpha and beta agonists was studied, before and after 24 hr of cold storage. Vascular and in vitro functional parameters were evaluated. We concluded that cold storage impairs partially the vascular alpha receptor. We could not find beta receptors under these conditions. An electron microscope analysis of these kidneys has shown some degree of autolysis of the tubular cells and good preservation of the vascular smooth muscle cells and membranes. These results are very important for kidney preservation before transplantation."}
{"id": "PMID:10226", "title": "Effect of colchicine and vinblastine on crayfish neuromuscular junction.", "content": "1. The effect of the microtubule disrupting agents colchicine and vinblastine was studied on crayfish excitatory neuromuscular transmission. 2. Colchicine, in concentrations of 1-3 mM, brought about a decrease in the amplitudes of intracellularly recorded excitatory junctional potentials (ejps). Vinblastine, in concentrations of 0.08-0.32 mM, increased the amplitudes of ejps. 3. Drug-induced alterations in ejp amplitude resulted from changes in quantal content of the excitattory nerve as determined by extracellular recording. The effect could not be explained by changes in quantal size. 4. The effect of colchicine and vinblastine does not appear to be related to an action on microtubules.", "contents": "Effect of colchicine and vinblastine on crayfish neuromuscular junction. 1. The effect of the microtubule disrupting agents colchicine and vinblastine was studied on crayfish excitatory neuromuscular transmission. 2. Colchicine, in concentrations of 1-3 mM, brought about a decrease in the amplitudes of intracellularly recorded excitatory junctional potentials (ejps). Vinblastine, in concentrations of 0.08-0.32 mM, increased the amplitudes of ejps. 3. Drug-induced alterations in ejp amplitude resulted from changes in quantal content of the excitattory nerve as determined by extracellular recording. The effect could not be explained by changes in quantal size. 4. The effect of colchicine and vinblastine does not appear to be related to an action on microtubules."}
{"id": "PMID:10227", "title": "Accumulation of chlorporomazine by subcellular fractions of rat brain.", "content": "1. The study of the in vitro accumulation of [3H] chlorpromazine that a state of rapid equilibrium was reached for subcellular particles from cortex, midbrain and hindbrain of rats. 2. This accumulation was not saturable by increasing the concentration of chlorpromazine, and the relationship between accumulation and concentration was not modified by temperature, preincubation with high concentration of unlabelled chlorpromazine or by lowering the fraction concentration. 3. The highest accumulation of radioactivity was seen in the midbrain region and the lowest in the hindbrain. 4. In the cortex and midbrain the membrane fraction showed the highest accumulation. 5. The effect of pH on the accumulation indicated that a significnat rise was seen between pH 8 and 5. 6. This factor could also be explained in terms of solubility of the drug in membranes. 7. Studies on the metabolic fate of the drug during incubation indicated that there was a fairly rapid breakdown during incubation, the highest being seen with mitochondrail fractions and the least with membrane procedures. 9. It is concluded that accumulation of chlorpromazine by subcellular fractions in vitro may be associated with solubility in membranes and that the picture  may be complicated by the presence of breakdown products.", "contents": "Accumulation of chlorporomazine by subcellular fractions of rat brain. 1. The study of the in vitro accumulation of [3H] chlorpromazine that a state of rapid equilibrium was reached for subcellular particles from cortex, midbrain and hindbrain of rats. 2. This accumulation was not saturable by increasing the concentration of chlorpromazine, and the relationship between accumulation and concentration was not modified by temperature, preincubation with high concentration of unlabelled chlorpromazine or by lowering the fraction concentration. 3. The highest accumulation of radioactivity was seen in the midbrain region and the lowest in the hindbrain. 4. In the cortex and midbrain the membrane fraction showed the highest accumulation. 5. The effect of pH on the accumulation indicated that a significnat rise was seen between pH 8 and 5. 6. This factor could also be explained in terms of solubility of the drug in membranes. 7. Studies on the metabolic fate of the drug during incubation indicated that there was a fairly rapid breakdown during incubation, the highest being seen with mitochondrail fractions and the least with membrane procedures. 9. It is concluded that accumulation of chlorpromazine by subcellular fractions in vitro may be associated with solubility in membranes and that the picture  may be complicated by the presence of breakdown products."}
{"id": "PMID:10229", "title": "[Effect of mutagenic metabolic activation of N-nitrosomorpholine on microorganisms].", "content": "Almost similar sensitivity is demonstrated of different methods of studying mutagenic metabolic activation of N-nitrosomorpholine (NM) in Salmonella typhimurium TA 1950 (host-mediated assay and the system of metabolic activation with rat liver homogenate). The role of correlation of certain ingredients of NM metabolic activation system with homogenates (homogenate and cofactor NADPH concentrations) is studied. The fact of influence of microsome protein activator (phenobarbital) on the NM mutagen activation effect is established.", "contents": "[Effect of mutagenic metabolic activation of N-nitrosomorpholine on microorganisms]. Almost similar sensitivity is demonstrated of different methods of studying mutagenic metabolic activation of N-nitrosomorpholine (NM) in Salmonella typhimurium TA 1950 (host-mediated assay and the system of metabolic activation with rat liver homogenate). The role of correlation of certain ingredients of NM metabolic activation system with homogenates (homogenate and cofactor NADPH concentrations) is studied. The fact of influence of microsome protein activator (phenobarbital) on the NM mutagen activation effect is established."}
{"id": "PMID:10230", "title": "Mechanisms of arrhythmias in chronic obstructive lung disease.", "content": "Because of the close anatomic and physiologic relationship between the heart and lungs, patients with chronic obstructive lung disease are at special risk of arrhythmias. Effective therapy hinges on identifying the mechanisms of the arrhythmias--hemodynamic, metabolic, or drug-induced. Impulsive use of antiarrhythmic agents may result only in a more complex and dangerous rhythm disorder. Extremes of pH are a major cause of arrhythmias in these patients. Respiratory alkalemia usually originates with inappropriate ventilation, often during mechanical respiration, while metabolic alkalemia generally can be traced to diuretic or bicarbonate therapy. Lidocaine or diphenylhydantoin are of little use, since the alkaline pH inside and outside heart muscle cells hampers drug distribution and activity. At the other extreme, the arrhythmias of acidemia strike patients who have severe respiratory failure with carbon dioxide retention or severe cardiac failure with shock and lactic acidemia. Arrhythmias may develop if vagal restraint is lost, which is especially likely in patients with potassium depletion. Irritant receptors along the bronchopulmonary tree can trigger arrhythmias if stimulated by cough, microembolism, or mechanical irritation, which is a hazard with endotracheal or tracheostomy tubes.", "contents": "Mechanisms of arrhythmias in chronic obstructive lung disease. Because of the close anatomic and physiologic relationship between the heart and lungs, patients with chronic obstructive lung disease are at special risk of arrhythmias. Effective therapy hinges on identifying the mechanisms of the arrhythmias--hemodynamic, metabolic, or drug-induced. Impulsive use of antiarrhythmic agents may result only in a more complex and dangerous rhythm disorder. Extremes of pH are a major cause of arrhythmias in these patients. Respiratory alkalemia usually originates with inappropriate ventilation, often during mechanical respiration, while metabolic alkalemia generally can be traced to diuretic or bicarbonate therapy. Lidocaine or diphenylhydantoin are of little use, since the alkaline pH inside and outside heart muscle cells hampers drug distribution and activity. At the other extreme, the arrhythmias of acidemia strike patients who have severe respiratory failure with carbon dioxide retention or severe cardiac failure with shock and lactic acidemia. Arrhythmias may develop if vagal restraint is lost, which is especially likely in patients with potassium depletion. Irritant receptors along the bronchopulmonary tree can trigger arrhythmias if stimulated by cough, microembolism, or mechanical irritation, which is a hazard with endotracheal or tracheostomy tubes."}
{"id": "PMID:10233", "title": "Social work training of new health professionals.", "content": "The Child Health Associate program provides a model for using social workers in the training of new health professionals. Administratively, social workers have contributed to curriculum development in the behavioral sciences. They have influenced decisions regarding student selection and have developed and implemented a faculty adviser program. Because of their practical experience as primary care practitioners, social workers have been able to define effectively the skills needed by the new professionals to meet the social and emotional needs of their patients. Social workers have made use of their contacts in hospitals and communities to design and implement courses and clinics that combine in a meaningful manner theoretical material and practical experiences in patient contact. Evaluative research in the area of interviewing skills and crisis management demonstrates that the teaching methods applied by the social work profession are effective in increasing the level of students' interviewing skills in clinical practice and help prepare them to recognize familiy crises.", "contents": "Social work training of new health professionals. The Child Health Associate program provides a model for using social workers in the training of new health professionals. Administratively, social workers have contributed to curriculum development in the behavioral sciences. They have influenced decisions regarding student selection and have developed and implemented a faculty adviser program. Because of their practical experience as primary care practitioners, social workers have been able to define effectively the skills needed by the new professionals to meet the social and emotional needs of their patients. Social workers have made use of their contacts in hospitals and communities to design and implement courses and clinics that combine in a meaningful manner theoretical material and practical experiences in patient contact. Evaluative research in the area of interviewing skills and crisis management demonstrates that the teaching methods applied by the social work profession are effective in increasing the level of students' interviewing skills in clinical practice and help prepare them to recognize familiy crises."}
{"id": "PMID:10234", "title": "[Experimental study on prediction of drug toxicity. Drug-induced hemolysis and lysosomes lysis in vitro].", "content": "The effect of drugs on isolated rat liver lysosomes, erythrocytes and some erythrocyte enzymes was studied in vitro. Many tranquilizers, antihistaminics and antidepressants, which are known to have the greatest number of adverse reactions in clinical use, had a lytic effect on the particle membranes at concentrations above 2 X 10(-4) M. The present study revealed a good correlation between the p.o. LD50 (rat and mouse) and H30 (molar concentration of drug causing 30% hemolysis). It is suggested, therefore, that the labilizing effect of drugs on rat erythrocytes is useful for testing the lytic action of drugs in vivo.", "contents": "[Experimental study on prediction of drug toxicity. Drug-induced hemolysis and lysosomes lysis in vitro]. The effect of drugs on isolated rat liver lysosomes, erythrocytes and some erythrocyte enzymes was studied in vitro. Many tranquilizers, antihistaminics and antidepressants, which are known to have the greatest number of adverse reactions in clinical use, had a lytic effect on the particle membranes at concentrations above 2 X 10(-4) M. The present study revealed a good correlation between the p.o. LD50 (rat and mouse) and H30 (molar concentration of drug causing 30% hemolysis). It is suggested, therefore, that the labilizing effect of drugs on rat erythrocytes is useful for testing the lytic action of drugs in vivo."}
{"id": "PMID:10235", "title": "[Action mechanisms of the contracting drugs, K, acetylcholine, histamine and Ba and of the antispasmodics, isoproterenol and papaverine in the isolated guinea pig ileum, particularly in relation to Ca].", "content": "Shapes of the contractions induced by K, acetylcholine (AHc), histamine and Ba consisted of the phasic contraction (PC) and the subsequent tonic contraction (TC). PCs by K, ACh and histamine are initiated by the release and the passive influx of Ca, whereas that by Ba is only initiated by the release of Ca. TCs by K, ACh and histamine are maintained by the active influx of Ca, whereas that by Ba is maintained by the active influx and the release of Ca. Storage sites of Ca in the cell membrane of this preparation can be divided into three; the first, the second and the third, which contain the loosely, the less loosely-, and the tightly-bound Ca, respectively. K releases Ca to elicit contraction from the first division, ACh or histamine does so from the first and second divisions, and Ba does so from all of the three divisions. Based on the influence of high K-depolarizing bath solution on the relaxations by isoproterenol (Iso) and papaverine (Pap) and the effects of Iso and Pap on the shapes of contractions by K, ACh, Ba and exogenous Ca, the following assumptions were made: antispasmodic action of Iso is produced by inhibition of cell membrane (inhibition of release and influx of Ca), whereas that by Pap is due to this inhibition followed by inhibition of the muscle contractile system with the increase of concentrations. The effects of Iso and Pap on the concentration-action curves of the contractions by K, ACh, Ba and exogenous Ca(Table II) suggest that the parallel shift to the right of the curves of K, ACh and Ba is due to the functional antagonism between the antispasmodics and the mobilization of Ca produced by the contracting agents.", "contents": "[Action mechanisms of the contracting drugs, K, acetylcholine, histamine and Ba and of the antispasmodics, isoproterenol and papaverine in the isolated guinea pig ileum, particularly in relation to Ca]. Shapes of the contractions induced by K, acetylcholine (AHc), histamine and Ba consisted of the phasic contraction (PC) and the subsequent tonic contraction (TC). PCs by K, ACh and histamine are initiated by the release and the passive influx of Ca, whereas that by Ba is only initiated by the release of Ca. TCs by K, ACh and histamine are maintained by the active influx of Ca, whereas that by Ba is maintained by the active influx and the release of Ca. Storage sites of Ca in the cell membrane of this preparation can be divided into three; the first, the second and the third, which contain the loosely, the less loosely-, and the tightly-bound Ca, respectively. K releases Ca to elicit contraction from the first division, ACh or histamine does so from the first and second divisions, and Ba does so from all of the three divisions. Based on the influence of high K-depolarizing bath solution on the relaxations by isoproterenol (Iso) and papaverine (Pap) and the effects of Iso and Pap on the shapes of contractions by K, ACh, Ba and exogenous Ca, the following assumptions were made: antispasmodic action of Iso is produced by inhibition of cell membrane (inhibition of release and influx of Ca), whereas that by Pap is due to this inhibition followed by inhibition of the muscle contractile system with the increase of concentrations. The effects of Iso and Pap on the concentration-action curves of the contractions by K, ACh, Ba and exogenous Ca(Table II) suggest that the parallel shift to the right of the curves of K, ACh and Ba is due to the functional antagonism between the antispasmodics and the mobilization of Ca produced by the contracting agents."}
{"id": "PMID:10236", "title": "[Action mechanism of dibenamine on the tonus and inhibition of drug-induced contraction of the isolated guinea pig ileum, with special reference to its relationship to Ca].", "content": "Dibenamine (DB) produced contraction due to influx and release of Ca in normal medium, whereas it produced relaxation of the K-induced contraction due to depression of the activity of the muscle cell membrane. DB inhibited active influx, passive influx and release of Ca induced by ACh in this order as the concentrations were increased and also inhibited the contraction by histamine selectively as compared with the contractions by ACh, K and Ba, the inhibition of the ACh-, K- and Ba-contractions being almost to the same degree. In addition, DB inhibited to much the same degree the phasic contraction(PC) and tonic contraction(TC) by histamine, whereas it inhibited TC in preference to PC induced by ACh, K and Ba. Irreversible inhibition by DB of ACh-, K- and Ba-induced contractions were protected by Ca, whereas those of histamine-induced contraction were selectively protected by histamine and antihistamine, but not by Ca. These results indicate that the antagonism of DB and its irreversibility against histamine may be due to blockade of the histaminergic receptor, whereas those against ACh, K and Ba may be due to inhibition of the Ca-site. Evidence has been obtained suggesting that the irreversible parallel shift to the right of the log concentration-action curve of histamine after washout of DB may be due to spare receptors, whereas that of ACh, K or Ba may be due to inhibition of the Ca-site.", "contents": "[Action mechanism of dibenamine on the tonus and inhibition of drug-induced contraction of the isolated guinea pig ileum, with special reference to its relationship to Ca]. Dibenamine (DB) produced contraction due to influx and release of Ca in normal medium, whereas it produced relaxation of the K-induced contraction due to depression of the activity of the muscle cell membrane. DB inhibited active influx, passive influx and release of Ca induced by ACh in this order as the concentrations were increased and also inhibited the contraction by histamine selectively as compared with the contractions by ACh, K and Ba, the inhibition of the ACh-, K- and Ba-contractions being almost to the same degree. In addition, DB inhibited to much the same degree the phasic contraction(PC) and tonic contraction(TC) by histamine, whereas it inhibited TC in preference to PC induced by ACh, K and Ba. Irreversible inhibition by DB of ACh-, K- and Ba-induced contractions were protected by Ca, whereas those of histamine-induced contraction were selectively protected by histamine and antihistamine, but not by Ca. These results indicate that the antagonism of DB and its irreversibility against histamine may be due to blockade of the histaminergic receptor, whereas those against ACh, K and Ba may be due to inhibition of the Ca-site. Evidence has been obtained suggesting that the irreversible parallel shift to the right of the log concentration-action curve of histamine after washout of DB may be due to spare receptors, whereas that of ACh, K or Ba may be due to inhibition of the Ca-site."}
{"id": "PMID:10239", "title": "Effect of hypophysectomy and insulin on lipogenesis in cockerels.", "content": "Hypophysectomy increases hepatic lipogenesis in cockerels. In an attempt to find the possible hormonal mechanism for this we have examined the effects of hypophysectomy, insulin and pituitary homogenates on hepatic lipogenesis. Insulin (5 U/kg) injected intravenously, simultaneously with glucose-14C tracer, increased the amount of 14C found in liver lipids at 30 min after the injection. Similarly, insulin injected 5 min before killing, increased the incorporation of glucose-14C and acetate-14C by liver slices during a 30 min incubation. Hypophysectomy increased lipogenesis within 24 hours. The effect of insulin was most pronounced in hypophysectomized cockerels. The activity of the lipogenic enzyme, acetyl CoA carboxylase was similarly affected. A homogenate of chicken pituitaries added to the medium reduced lipid synthesis from glucose-14C by liver slices. This effect was larger in liver slices in which lipogenesis had been stimulated by insulin. The increased rate of hepatic lipgenesis in hypophysectomized cockerels may be caused partly by increased hepatic sensitivity to the lipogenic action of insulin or by the removal of a direct inhibition by pituitary hormones.", "contents": "Effect of hypophysectomy and insulin on lipogenesis in cockerels. Hypophysectomy increases hepatic lipogenesis in cockerels. In an attempt to find the possible hormonal mechanism for this we have examined the effects of hypophysectomy, insulin and pituitary homogenates on hepatic lipogenesis. Insulin (5 U/kg) injected intravenously, simultaneously with glucose-14C tracer, increased the amount of 14C found in liver lipids at 30 min after the injection. Similarly, insulin injected 5 min before killing, increased the incorporation of glucose-14C and acetate-14C by liver slices during a 30 min incubation. Hypophysectomy increased lipogenesis within 24 hours. The effect of insulin was most pronounced in hypophysectomized cockerels. The activity of the lipogenic enzyme, acetyl CoA carboxylase was similarly affected. A homogenate of chicken pituitaries added to the medium reduced lipid synthesis from glucose-14C by liver slices. This effect was larger in liver slices in which lipogenesis had been stimulated by insulin. The increased rate of hepatic lipgenesis in hypophysectomized cockerels may be caused partly by increased hepatic sensitivity to the lipogenic action of insulin or by the removal of a direct inhibition by pituitary hormones."}
{"id": "PMID:10240", "title": "Effects of lithium on inducible enzymes of rat liver.", "content": "Chronic lithium administration to female rats results in elevation of serum corticoids, lowering of serum glucose and altered induction of liver enzymes. The cortisol induction of tyrosine transaminase is increased selectively over that of tryptophan oxygenase. The glucose induction of glucokinase following a fast is increased by chronic lithium treatment but diminished by acute treatment. These results indicate that lithium may alter the glucose metabolic set-point in rats.", "contents": "Effects of lithium on inducible enzymes of rat liver. Chronic lithium administration to female rats results in elevation of serum corticoids, lowering of serum glucose and altered induction of liver enzymes. The cortisol induction of tyrosine transaminase is increased selectively over that of tryptophan oxygenase. The glucose induction of glucokinase following a fast is increased by chronic lithium treatment but diminished by acute treatment. These results indicate that lithium may alter the glucose metabolic set-point in rats."}
{"id": "PMID:10242", "title": "[Metabolism of nicotinic acid in plant cell suspension cultures: II; Isolation, characterization and enzymology of nicotinic acid N-alpha-arabinoside (author's transl)].", "content": "A very hydrophilic compound was isolated from parsley cell suspension cultures in high yield after application of nicotinic acid. Using chemical, chromatographic and spectroscopic procedures the structure of this new plant constituent has been elucidated as nicotinic acid N-alpha-L-arabinopyranoside. This structure has been proved by chemical synthesis. An arabinosyltransferase was isolated from parsley cell suspension cultures and purified about 19-fold. The enzyme converted nicotinic acid N-alpha-arabinoside with UDP to nicotinic acid and UDP-arabinose. pH-Optimum (pH 7.0-8.0), Km value for nicotinic acid N-alpha-L-arabinoside (2.2 X 10(-4) mol/l) and mol. wt. (app. 70 000) of the transferase were measured. Function and biosynthesis of the arabinoside in cell cultures are discussed.", "contents": "[Metabolism of nicotinic acid in plant cell suspension cultures: II; Isolation, characterization and enzymology of nicotinic acid N-alpha-arabinoside (author's transl)]. A very hydrophilic compound was isolated from parsley cell suspension cultures in high yield after application of nicotinic acid. Using chemical, chromatographic and spectroscopic procedures the structure of this new plant constituent has been elucidated as nicotinic acid N-alpha-L-arabinopyranoside. This structure has been proved by chemical synthesis. An arabinosyltransferase was isolated from parsley cell suspension cultures and purified about 19-fold. The enzyme converted nicotinic acid N-alpha-arabinoside with UDP to nicotinic acid and UDP-arabinose. pH-Optimum (pH 7.0-8.0), Km value for nicotinic acid N-alpha-L-arabinoside (2.2 X 10(-4) mol/l) and mol. wt. (app. 70 000) of the transferase were measured. Function and biosynthesis of the arabinoside in cell cultures are discussed."}
{"id": "PMID:10243", "title": "Chemical modification of two tryptophan residues abolishes the catalytic activity of aminoacylase.", "content": "1) The reaction of 1 H-diazotetrazole and N-bromosuccinimide with aminoacylase was studied under different conditions. A tenfold molar excess of 1 H-diazotetrazole (2 X 10(-4) M) at pH 5.5 abolishes the catalytic activity of the enzyme while modifying only two tryptophan residues. No other amino acid reacted under these conditions as tested by amino acid analysis. 2) With a 40-fold molar excess of N-bromosuccinimide (8 X 10(-4)M) at pH 5.0, two tryptophan residues of the enzyme were oxidized with complete loss of activity. Under these conditions no significant cleavage of the polypeptide chain was observed. Neither tyrosine nor histidine was modified by this reagent, up to a 100-fold molar excess. 3) Substrates and reversible (N-tosylalanine) and irreversible (TosPheCH2Cl) inhibitors of the enzyme do not protect the two reactive tryptophans against the modification reagents. Under more drastic conditions, lysine, tyrosine and histidine residues are also modified by the reagents.", "contents": "Chemical modification of two tryptophan residues abolishes the catalytic activity of aminoacylase. 1) The reaction of 1 H-diazotetrazole and N-bromosuccinimide with aminoacylase was studied under different conditions. A tenfold molar excess of 1 H-diazotetrazole (2 X 10(-4) M) at pH 5.5 abolishes the catalytic activity of the enzyme while modifying only two tryptophan residues. No other amino acid reacted under these conditions as tested by amino acid analysis. 2) With a 40-fold molar excess of N-bromosuccinimide (8 X 10(-4)M) at pH 5.0, two tryptophan residues of the enzyme were oxidized with complete loss of activity. Under these conditions no significant cleavage of the polypeptide chain was observed. Neither tyrosine nor histidine was modified by this reagent, up to a 100-fold molar excess. 3) Substrates and reversible (N-tosylalanine) and irreversible (TosPheCH2Cl) inhibitors of the enzyme do not protect the two reactive tryptophans against the modification reagents. Under more drastic conditions, lysine, tyrosine and histidine residues are also modified by the reagents."}
{"id": "PMID:10244", "title": "Studies on ribonucleic acid metabolism using nuclear columns. Release of rapidly labeled RNA from rat liver nuclei.", "content": "A method is described to study the effect of successively changing incubation conditions on the release of rapidly labeled RNA from isolated nuclei. Nuclear columns containing immobilized rat liver nuclei isolated after in vivo application of labeled orotic acid are perfused with different non-radioactive media. Within the course of one perfusion, the rate of RNA release can be repeatedly altered by variation of temperature, acidity and concentrations of nucleoside triphosphates, complexing agents, sodium chloride and manganese chloride. RNA release can be started and stopped, indicating that the reaction does not result from damage to nuclei. During 60 min perfusion the same product, labeled ribonucleoprotein (sigma = 1.43 g/cm3 in CsCl), is released. High release rates depend on the ratio of nucleoside triphosphate to divalent cation concentration, not on the concentration of the agents per se. Ribonucleoside and deoxyribonucleoside triphosphates exert the same effect as ATP. The SH reagents iodoacetamide and iodoacetate only slightly affect the ATP-induced reaction. In contrast, p-chloromercuribenzoate, after an initial stimulation, causes inhibition of RNA release.", "contents": "Studies on ribonucleic acid metabolism using nuclear columns. Release of rapidly labeled RNA from rat liver nuclei. A method is described to study the effect of successively changing incubation conditions on the release of rapidly labeled RNA from isolated nuclei. Nuclear columns containing immobilized rat liver nuclei isolated after in vivo application of labeled orotic acid are perfused with different non-radioactive media. Within the course of one perfusion, the rate of RNA release can be repeatedly altered by variation of temperature, acidity and concentrations of nucleoside triphosphates, complexing agents, sodium chloride and manganese chloride. RNA release can be started and stopped, indicating that the reaction does not result from damage to nuclei. During 60 min perfusion the same product, labeled ribonucleoprotein (sigma = 1.43 g/cm3 in CsCl), is released. High release rates depend on the ratio of nucleoside triphosphate to divalent cation concentration, not on the concentration of the agents per se. Ribonucleoside and deoxyribonucleoside triphosphates exert the same effect as ATP. The SH reagents iodoacetamide and iodoacetate only slightly affect the ATP-induced reaction. In contrast, p-chloromercuribenzoate, after an initial stimulation, causes inhibition of RNA release."}
{"id": "PMID:10245", "title": "[Hydroxylation of testosterone and 5alpha-dihydrotestosterone--isolation of 2alpha-hydroxytestosterone (author's transl)].", "content": "The hydroxylation at C-2 of testosterone and 5alpha-dihydrotestosterone is measured by isolation of HTO after incubating \"metabolically labile\" tritium labeled steroids with the enzymes. After hydroxylation of testosterone in rat liver 2alpha-hydroxytestosterone was isolated and identified by gaschromatography and mass spectra.", "contents": "[Hydroxylation of testosterone and 5alpha-dihydrotestosterone--isolation of 2alpha-hydroxytestosterone (author's transl)]. The hydroxylation at C-2 of testosterone and 5alpha-dihydrotestosterone is measured by isolation of HTO after incubating \"metabolically labile\" tritium labeled steroids with the enzymes. After hydroxylation of testosterone in rat liver 2alpha-hydroxytestosterone was isolated and identified by gaschromatography and mass spectra."}
{"id": "PMID:10246", "title": "The activator of cerebroside sulphatase. Lysosomal localization.", "content": "1) An activator protein necessary for the enzymic hydrolysis of cerebroside sulphate could be partially purified from unfractionated rat liver. This activator, which is similar to that of human origin, proved to be a heat-stable, non-dialyzable, low molecular weight protein with an isoelectric point of 4.1. Its activity could be destroyed by pronase. 2) For elucidation of the subcellular localization of the activator, rat liver was fractionated by differential centrifugation. The intracellular distribution of the cerebroside sulphatase activator was compared to the distribution patterns of marker enzymes for different cell organelles and found to coincide with the lysosomal arylsulphatase, thus indicating a lysosomal localization. 3) This was confirmed using highly purified secondary, i.e. iron-loaded, lysosomes. After disruption by osmotic shock, these organelles hydrolyzed cerebroside sulphate when incubations were performed under physiological conditions with endogenous as well as exogenous sulphatase A as enzyme. 4) After subfractionation of the disrupted secondary lysosomes into membrane and lysosol fractions by high speed centrifugation, it was found that the activator protein was exclusively associated with the lysosol, whereas the acid hydrolases were distributed differently between the two fractions. 5) The lysosol was further fractionated by semi-preparative electrophoresis on polyacrylamide gels. Two protein fractions were obtained: a high molecular weight fraction, containing the activator-free acid hydrolases, and a low molecular weight fraction, containing the enzyme-free activator of cerebroside sulphatase. 6) The significance of these findings for the hydrolysis of sphingolipids in the lysosomes is discussed.", "contents": "The activator of cerebroside sulphatase. Lysosomal localization. 1) An activator protein necessary for the enzymic hydrolysis of cerebroside sulphate could be partially purified from unfractionated rat liver. This activator, which is similar to that of human origin, proved to be a heat-stable, non-dialyzable, low molecular weight protein with an isoelectric point of 4.1. Its activity could be destroyed by pronase. 2) For elucidation of the subcellular localization of the activator, rat liver was fractionated by differential centrifugation. The intracellular distribution of the cerebroside sulphatase activator was compared to the distribution patterns of marker enzymes for different cell organelles and found to coincide with the lysosomal arylsulphatase, thus indicating a lysosomal localization. 3) This was confirmed using highly purified secondary, i.e. iron-loaded, lysosomes. After disruption by osmotic shock, these organelles hydrolyzed cerebroside sulphate when incubations were performed under physiological conditions with endogenous as well as exogenous sulphatase A as enzyme. 4) After subfractionation of the disrupted secondary lysosomes into membrane and lysosol fractions by high speed centrifugation, it was found that the activator protein was exclusively associated with the lysosol, whereas the acid hydrolases were distributed differently between the two fractions. 5) The lysosol was further fractionated by semi-preparative electrophoresis on polyacrylamide gels. Two protein fractions were obtained: a high molecular weight fraction, containing the activator-free acid hydrolases, and a low molecular weight fraction, containing the enzyme-free activator of cerebroside sulphatase. 6) The significance of these findings for the hydrolysis of sphingolipids in the lysosomes is discussed."}
{"id": "PMID:10259", "title": "Blastogenic response of human lymphocytes to oral bacterial antigens: comparison of individuals with periodontal disease to normal and edentulous subjects.", "content": "Cell-mediated immunity in humans to antigens derived from oral plaque bacteria was investigated by using the lymphocyte blastogenesis assay. Subjects with varying severities of periodontal disease including normal, gingivitis, periodontitis, and edentulous were compared. Mononuclear leukocytes were separated from peripheral blood and cultured with antigens prepared by sonication of Actinomyces viscosus (AV), Actinomyces naeslundii (AN), Veillonella alcalescens (VA), Leptotrichia buccalis (LB), Bacteroides melaninogenicus (BM), and homologous dental plaque (DP). The lymphocyte response of subjects with gingivitis or periodontitis was significantly greater than that of normal subjects to antigens of AV, AN, and DP, but did not differ from the response of edentulous subjects. Periodontitis subjects were significantly more reactive than edentulous and normal subjects in response to VA, LB, and BM. These findings suggest that the tested gram-negative bacteria and the host response they evoke are associated with advanced periodontal destruction.", "contents": "Blastogenic response of human lymphocytes to oral bacterial antigens: comparison of individuals with periodontal disease to normal and edentulous subjects. Cell-mediated immunity in humans to antigens derived from oral plaque bacteria was investigated by using the lymphocyte blastogenesis assay. Subjects with varying severities of periodontal disease including normal, gingivitis, periodontitis, and edentulous were compared. Mononuclear leukocytes were separated from peripheral blood and cultured with antigens prepared by sonication of Actinomyces viscosus (AV), Actinomyces naeslundii (AN), Veillonella alcalescens (VA), Leptotrichia buccalis (LB), Bacteroides melaninogenicus (BM), and homologous dental plaque (DP). The lymphocyte response of subjects with gingivitis or periodontitis was significantly greater than that of normal subjects to antigens of AV, AN, and DP, but did not differ from the response of edentulous subjects. Periodontitis subjects were significantly more reactive than edentulous and normal subjects in response to VA, LB, and BM. These findings suggest that the tested gram-negative bacteria and the host response they evoke are associated with advanced periodontal destruction."}
{"id": "PMID:10260", "title": "Prevention of benzo(a)pyrene-induced mutagenicity by homogeneous epoxide hydratase.", "content": "Benzo(a)pyrene and benz(a) anthrancene which, in contrast to the K-region epoxides benzo(a)pyrene 4,5-oxide and benz(a)anthracene 5,6-oxide, are not mutagenic to Salmonella typhimurium TA 1537 in the absence of mammalian enzyme preparations, were activated by liver microsomes from C3H mice, which had not received any pretreatment, to mutagens reverting this tester strain to histidine prototrophy. Addition of epoxide hydratase inhibitors greatly increased this mutagenicity and addition of pure epoxide hydratase reduced it by more than 95% down to the range of spontaneous mutations as observed in absence of any added mutagen. This demonstrates than the metabolic pathway responsible for the mutagenicity of both polycyclic hydrocarbons observed in this system proceeds entirely via an epoxidation pathway and that the responsible metabolites are epoxides or species arising from them. Moreover, further metabolism by epoxide hydratase does not lead to produce contributing to the mutagenicity observed with the tester strain used. Finally, the epoxides relevant for the observed mutagenicity are substrates for epoxide hydratase; indeed, modest amounts of the pure enzyme can prevent the mutagenic effect.", "contents": "Prevention of benzo(a)pyrene-induced mutagenicity by homogeneous epoxide hydratase. Benzo(a)pyrene and benz(a) anthrancene which, in contrast to the K-region epoxides benzo(a)pyrene 4,5-oxide and benz(a)anthracene 5,6-oxide, are not mutagenic to Salmonella typhimurium TA 1537 in the absence of mammalian enzyme preparations, were activated by liver microsomes from C3H mice, which had not received any pretreatment, to mutagens reverting this tester strain to histidine prototrophy. Addition of epoxide hydratase inhibitors greatly increased this mutagenicity and addition of pure epoxide hydratase reduced it by more than 95% down to the range of spontaneous mutations as observed in absence of any added mutagen. This demonstrates than the metabolic pathway responsible for the mutagenicity of both polycyclic hydrocarbons observed in this system proceeds entirely via an epoxidation pathway and that the responsible metabolites are epoxides or species arising from them. Moreover, further metabolism by epoxide hydratase does not lead to produce contributing to the mutagenicity observed with the tester strain used. Finally, the epoxides relevant for the observed mutagenicity are substrates for epoxide hydratase; indeed, modest amounts of the pure enzyme can prevent the mutagenic effect."}
{"id": "PMID:10261", "title": "The intraocular pressure response of conscious rabbits to clonidine.", "content": "A study has been made of the time courses of the pupillary and intraocular pressure responses of conscious rabbits to clonidine administered either topically or intravenously. Topical unilateral application of clonidine caused transient pupil dilatation and a biphasic intraocular pressure response; an initial hypertensive response preceded a hypotensive phase lasting several hours. Pupillary and hypertensive responses were absent in the untreated eye, but there was a rapid decrease of intraocular pressure. Intravenous administration of clonidine caused an immediate and large decrease of intraocular pressure in both eyes. Phenoxybenzamine given intravenously inhibited the pupillary dilatation and the hypertensive responses to clonidine. The role of efferent adrenergic neuronal activity in mediating the local biphasic pressure response was studied in rabbits with unilateral precervical and postcervical sympathotomy. The results showed the hypotensive response to be dependent on an intact adrenergic innervation of the ocular tissues.", "contents": "The intraocular pressure response of conscious rabbits to clonidine. A study has been made of the time courses of the pupillary and intraocular pressure responses of conscious rabbits to clonidine administered either topically or intravenously. Topical unilateral application of clonidine caused transient pupil dilatation and a biphasic intraocular pressure response; an initial hypertensive response preceded a hypotensive phase lasting several hours. Pupillary and hypertensive responses were absent in the untreated eye, but there was a rapid decrease of intraocular pressure. Intravenous administration of clonidine caused an immediate and large decrease of intraocular pressure in both eyes. Phenoxybenzamine given intravenously inhibited the pupillary dilatation and the hypertensive responses to clonidine. The role of efferent adrenergic neuronal activity in mediating the local biphasic pressure response was studied in rabbits with unilateral precervical and postcervical sympathotomy. The results showed the hypotensive response to be dependent on an intact adrenergic innervation of the ocular tissues."}
{"id": "PMID:10262", "title": "The effect of miotics on the intraocular pressure of conscious owl monkeys.", "content": "The intraocular pressure of conscious, unsedated owl monkeys (Aotus trivirgatus) was measured with an applanation tonometer. Untreated eyes of the conscious animals were found to have higher values than those reported for owl monkeys anesthetized with pentobarbitone. Locally applied pilocarpine, carbachol, and oxotremorine gave concentration-related reduction in pressure, oxotremorine being the most potent and having longer duration of effect than the other compounds. Slight reductions were also observed with aceclidine and R. S. 86. These results are discussed in relation to the effects of miotics in man.", "contents": "The effect of miotics on the intraocular pressure of conscious owl monkeys. The intraocular pressure of conscious, unsedated owl monkeys (Aotus trivirgatus) was measured with an applanation tonometer. Untreated eyes of the conscious animals were found to have higher values than those reported for owl monkeys anesthetized with pentobarbitone. Locally applied pilocarpine, carbachol, and oxotremorine gave concentration-related reduction in pressure, oxotremorine being the most potent and having longer duration of effect than the other compounds. Slight reductions were also observed with aceclidine and R. S. 86. These results are discussed in relation to the effects of miotics in man."}
{"id": "PMID:10263", "title": "Interaction of Listeria monocytogenes and influenza in an animal model.", "content": "This study was designed to investigate the effects of viruses in the pathogenesis of Listeria monocytogenes. The organisms used in this study were: Listeria monocytogenes Type 1 isolated from a local fatal case; Mouse adapted influenza A/PR8/34 (HONI); Streptococcus pneumoniae Group B (U.M. Med. Ctr.) and poliovirus Type 2 MEF--G3M2. Balb-C mice were inoculated intraperitoneally with one LD50 of Listeria monocytogenes. Ten days later, the survivors were challenged intransally with 10 LD50 of influenza virus and observed for 14 days. Another set of Balb-C mice was inoculated intranasally with one LD50 of influenza virus and the survivors challenged 14 days later intraperitoneally with 10 LD50 of Listeria monocytogenes. Controls consisted of similar inoculation and challenge methods in mice using Streptococcus pneumoniae and polio virus with Listeria monocytogenes and influenza virus. Cross protection was observed only between Listeria monocytogenes and influenza virus. Cellular immunity may play a role in this interaction. This findings seem to agree with reports from others who showed cross protection between Listeria monocytogenes and other intracellular bacteria and parasites.", "contents": "Interaction of Listeria monocytogenes and influenza in an animal model. This study was designed to investigate the effects of viruses in the pathogenesis of Listeria monocytogenes. The organisms used in this study were: Listeria monocytogenes Type 1 isolated from a local fatal case; Mouse adapted influenza A/PR8/34 (HONI); Streptococcus pneumoniae Group B (U.M. Med. Ctr.) and poliovirus Type 2 MEF--G3M2. Balb-C mice were inoculated intraperitoneally with one LD50 of Listeria monocytogenes. Ten days later, the survivors were challenged intransally with 10 LD50 of influenza virus and observed for 14 days. Another set of Balb-C mice was inoculated intranasally with one LD50 of influenza virus and the survivors challenged 14 days later intraperitoneally with 10 LD50 of Listeria monocytogenes. Controls consisted of similar inoculation and challenge methods in mice using Streptococcus pneumoniae and polio virus with Listeria monocytogenes and influenza virus. Cross protection was observed only between Listeria monocytogenes and influenza virus. Cellular immunity may play a role in this interaction. This findings seem to agree with reports from others who showed cross protection between Listeria monocytogenes and other intracellular bacteria and parasites."}
{"id": "PMID:10266", "title": "[The symptomatic treatment of seasonal allergic rhinitis (author's transl)].", "content": "The aetiology, pathophysiology and symptomatology of seasonal rhinitis are briefly presented. Symptomatic therapy with antihistamines, nasal decongestants and local and systemic corticosteroids is critically discussed. The results of a trial with Disodium cromoglycate are reported. This is shown to be a valuable drug in the symptomatic management of seasonal rhinitis. It should be tried before resorting to steroid therapy.", "contents": "[The symptomatic treatment of seasonal allergic rhinitis (author's transl)]. The aetiology, pathophysiology and symptomatology of seasonal rhinitis are briefly presented. Symptomatic therapy with antihistamines, nasal decongestants and local and systemic corticosteroids is critically discussed. The results of a trial with Disodium cromoglycate are reported. This is shown to be a valuable drug in the symptomatic management of seasonal rhinitis. It should be tried before resorting to steroid therapy."}
{"id": "PMID:10267", "title": "Male pseudohermaphroditism, cryptorchism, and Sertoli cell neoplasia in three miniature Schnauzers.", "content": "A syndrome of male pseudohermaphroditism, cryptorchidism, and testicular neoplasia was diagnosed in 3 Miniature Schnauzers. The dogs had clinical signs of hyperestrogenism and were either unilateral or bilateral cryptorchids. At surgery, it was discovered that the dogs were male pseudohermaphrodites, having intra-abdominal testes containing Sertoli cell tumors and uteri that had undergone endometrial cystic hyperplasia.", "contents": "Male pseudohermaphroditism, cryptorchism, and Sertoli cell neoplasia in three miniature Schnauzers. A syndrome of male pseudohermaphroditism, cryptorchidism, and testicular neoplasia was diagnosed in 3 Miniature Schnauzers. The dogs had clinical signs of hyperestrogenism and were either unilateral or bilateral cryptorchids. At surgery, it was discovered that the dogs were male pseudohermaphrodites, having intra-abdominal testes containing Sertoli cell tumors and uteri that had undergone endometrial cystic hyperplasia."}
{"id": "PMID:10268", "title": "Observations on immobilization of P\u00e8re David's deer.", "content": "Etorphine and xylazine were found to be a safe and reliable drug combination for the immobilization of P\u00e8re David's deer, whether excited or unexcited. Excited deer had a longer preimmobilization period, when compared with unexcited deer at comparable dosages. Generally, the acid-base status of P\u00e8re David's deer during immobilization was not seriously altered. Deer that had been excited and exercised experienced mild respiratory problems; the unexcited, relatively calm deer experienced minimal acidosis. Significantly high pH and PO2 and significantly lower PCO2 and bicarbonate values were found in the excited deer, when compared with the unexcited deer. Rapid physiologic changes occurred after the intravenous administration of the antagonist, diprenorphine.", "contents": "Observations on immobilization of P\u00e8re David's deer. Etorphine and xylazine were found to be a safe and reliable drug combination for the immobilization of P\u00e8re David's deer, whether excited or unexcited. Excited deer had a longer preimmobilization period, when compared with unexcited deer at comparable dosages. Generally, the acid-base status of P\u00e8re David's deer during immobilization was not seriously altered. Deer that had been excited and exercised experienced mild respiratory problems; the unexcited, relatively calm deer experienced minimal acidosis. Significantly high pH and PO2 and significantly lower PCO2 and bicarbonate values were found in the excited deer, when compared with the unexcited deer. Rapid physiologic changes occurred after the intravenous administration of the antagonist, diprenorphine."}
{"id": "PMID:10269", "title": "The proliferation of transplanted haematopoietic cells derived from bone marrow and fetal liver.", "content": "The proliferation of transplanted murine haematopoietic cells, derived from the femoral bone marrow of young adults and from the liver on the sixteenth day of gestation, has been compared under standardized conditions. Suspensions of bone marrow cells contained 9-6+/-0-9 CFU per 10(5) cells (sm) and suspensions of fetal liver cells contained 3-7+/-0-5 CFU per 10(5) cells (Sl).Sl/Sm = 0-4. The mean diameter of colonies established by cells derived from bone marrow was 1-3+/-0-3 mm (established mean volume, Vm = 1-2 mm3) and the mean diameter of colonies established by cells derived from fetal liver was 1-7+/-0-1 mm (estimated mean volume, Vl ;-6 mm3). Vl/Vm ;-2. The relationship between the weight of the spleen and the number of bone marrow cells injected into lethally irradiated recipients 10 days previously has been confirmed, and a similar relationship between the weight of the spleen and the number of fetal liver cells injected has been demonstrated. An arbitrarily defined difference of 50 mg between the weight of the spleen in untreated irradiated controls and the weight of the spleen in irradiated recipients of haematopoietic cells has been observed 10 days after the administration of 2-2 x 10(6) bone marrow cells (Dm) or 3-0 x 10(6) fetal liver cells (Dl). Dm/Dl = 0-7. The calculated values of Dm/Dl (relative proliferative capacity), Sl/Sm (relative stem cell content) and Vl/Vm (relative clone size) are in good agreement with the values estimated using the equation Dm/Dl = Sl/Sm x Vl/Vm.", "contents": "The proliferation of transplanted haematopoietic cells derived from bone marrow and fetal liver. The proliferation of transplanted murine haematopoietic cells, derived from the femoral bone marrow of young adults and from the liver on the sixteenth day of gestation, has been compared under standardized conditions. Suspensions of bone marrow cells contained 9-6+/-0-9 CFU per 10(5) cells (sm) and suspensions of fetal liver cells contained 3-7+/-0-5 CFU per 10(5) cells (Sl).Sl/Sm = 0-4. The mean diameter of colonies established by cells derived from bone marrow was 1-3+/-0-3 mm (established mean volume, Vm = 1-2 mm3) and the mean diameter of colonies established by cells derived from fetal liver was 1-7+/-0-1 mm (estimated mean volume, Vl ;-6 mm3). Vl/Vm ;-2. The relationship between the weight of the spleen and the number of bone marrow cells injected into lethally irradiated recipients 10 days previously has been confirmed, and a similar relationship between the weight of the spleen and the number of fetal liver cells injected has been demonstrated. An arbitrarily defined difference of 50 mg between the weight of the spleen in untreated irradiated controls and the weight of the spleen in irradiated recipients of haematopoietic cells has been observed 10 days after the administration of 2-2 x 10(6) bone marrow cells (Dm) or 3-0 x 10(6) fetal liver cells (Dl). Dm/Dl = 0-7. The calculated values of Dm/Dl (relative proliferative capacity), Sl/Sm (relative stem cell content) and Vl/Vm (relative clone size) are in good agreement with the values estimated using the equation Dm/Dl = Sl/Sm x Vl/Vm."}
{"id": "PMID:10273", "title": "Metabolism of DL-(+/-)-phenylalanine by Aspergillus niger.", "content": "A fungus capable of degrading DL-phenylalanine was isolated from the soil and identified as Aspergillus niger. It was found to metabolize DL-phenylalanine by a new pathway involving 4-hydroxymandelic acid. D-Amino acid oxidase and L-phenylalanine: 2-oxoglutaric acid aminotransferase initiated the degradation of D- and L-phenylalanine, respectively. Both phenylpyruvate oxidase and phenylpyruvate decarboxylase activities could be demonstrated in the cell-free system. Phenylacetate hydroxylase, which required reduced nicotinamide adenine dinucleotide phosphate, converted phenylacetic acid to 2- and 4-hydroxyphenylacetic acid. Although 4-hydroxyphenylacetate was converted to 4-hydroxymandelate, 2-hydroxyphenylacetate was not utilized until the onset of sporulation. During sporulation, it was converted rapidly into homogentisate and oxidized to ring-cleaved products. 4-Hydroxymandelate was degraded to protocatechuate via 4-hydroxybenzoylformate, 4-hydroxybenzaldehyde, and 4-hydroxybenzoate.", "contents": "Metabolism of DL-(+/-)-phenylalanine by Aspergillus niger. A fungus capable of degrading DL-phenylalanine was isolated from the soil and identified as Aspergillus niger. It was found to metabolize DL-phenylalanine by a new pathway involving 4-hydroxymandelic acid. D-Amino acid oxidase and L-phenylalanine: 2-oxoglutaric acid aminotransferase initiated the degradation of D- and L-phenylalanine, respectively. Both phenylpyruvate oxidase and phenylpyruvate decarboxylase activities could be demonstrated in the cell-free system. Phenylacetate hydroxylase, which required reduced nicotinamide adenine dinucleotide phosphate, converted phenylacetic acid to 2- and 4-hydroxyphenylacetic acid. Although 4-hydroxyphenylacetate was converted to 4-hydroxymandelate, 2-hydroxyphenylacetate was not utilized until the onset of sporulation. During sporulation, it was converted rapidly into homogentisate and oxidized to ring-cleaved products. 4-Hydroxymandelate was degraded to protocatechuate via 4-hydroxybenzoylformate, 4-hydroxybenzaldehyde, and 4-hydroxybenzoate."}
{"id": "PMID:10274", "title": "Microbial oxidation of methane and methanol: crystallization and properties of methanol dehydrogenase from Methylosinus sporium.", "content": "Obligate methylotrophs are divisible into two types on the basis of ultrastructural biochemical characteristics. Both groups possess a soluble phenazine methosulfate (PMS)-dependent methanol dehydrogenase. In addition, particulate PMS-dependent methanol dehydrogenase and PMS-independent methanol oxidase have been found in the type I membrane group. A procedure was developed for the crystallization of methanol dehydrogenase from the soluble fraction of the type II obligate methylotroph Methylosinus sporium. This is the first report of a crystalline methanol dehydrogenase from a methylotrophic bacterium. The crystallized enzyme is homogeneous as judged by ultracentrifugation and by acrylamide gel electrophoresis. In the presence of an electron acceptor (phenazine or phenazinium compound) and an activator (ammonium compound), the crystallized enzyme catalyzed the oxidation of primary alcohols and formaldehyde. Secondary, tertiary, and aromatic alcohols were not oxidized. The molecular weight of the enzyme as estimated by gel filtration is approximately 60,000, and as estimated by sedimentation equilibrium analysis it is 62,000. The sedimentation constant (S20,W) is 2.9. The subunit size determined by sodium dodecyl sulfate-gel electrophoresis is approximately 60,000. The amino acid composition and spectral properties of the enzyme are also presented. Antisera prepared against the crystalline enzyme are nonspecific, they cross-reacted and inhibited isofunctional enzymes from other obligate methylotrophic bacteria.", "contents": "Microbial oxidation of methane and methanol: crystallization and properties of methanol dehydrogenase from Methylosinus sporium. Obligate methylotrophs are divisible into two types on the basis of ultrastructural biochemical characteristics. Both groups possess a soluble phenazine methosulfate (PMS)-dependent methanol dehydrogenase. In addition, particulate PMS-dependent methanol dehydrogenase and PMS-independent methanol oxidase have been found in the type I membrane group. A procedure was developed for the crystallization of methanol dehydrogenase from the soluble fraction of the type II obligate methylotroph Methylosinus sporium. This is the first report of a crystalline methanol dehydrogenase from a methylotrophic bacterium. The crystallized enzyme is homogeneous as judged by ultracentrifugation and by acrylamide gel electrophoresis. In the presence of an electron acceptor (phenazine or phenazinium compound) and an activator (ammonium compound), the crystallized enzyme catalyzed the oxidation of primary alcohols and formaldehyde. Secondary, tertiary, and aromatic alcohols were not oxidized. The molecular weight of the enzyme as estimated by gel filtration is approximately 60,000, and as estimated by sedimentation equilibrium analysis it is 62,000. The sedimentation constant (S20,W) is 2.9. The subunit size determined by sodium dodecyl sulfate-gel electrophoresis is approximately 60,000. The amino acid composition and spectral properties of the enzyme are also presented. Antisera prepared against the crystalline enzyme are nonspecific, they cross-reacted and inhibited isofunctional enzymes from other obligate methylotrophic bacteria."}
{"id": "PMID:10275", "title": "Mutant strains (nit) of Salmonella typhimurium with a pleiotropic defect in nitrogen metabolism.", "content": "We have isolated mutant strains (nit) of Salmonella typhimurium that are defective in nitrogen metabolism. They have a reduced ability to use a variety of compounds including glutamate, proline, arginine, N-acetyl-glucosamine, alanine, and adenosine as sole nitrogen source. In addition, although they grow normally on high concentrations of ammonium chloride (greater than 1 mM) as nitrogen source, they grow substantially more slowly than wild type at low concentrations (less than 1 mM). We postulated that the inability of these strains to utilize low concentrations of ammonium chloride accounts for their poor growth on other nitrogen sources. The specific biochemical lesion in strains with a nit mutation is not known; however, mutant strains have no detectable alteration in the activities of glutamine synthetase, glutamate synthetase, or glutamate dehydrogenase, the enzymes known to be involved in assimilation of ammonia. A nit mutation is suppressed by second-site mutations in the structural gene for glutamine synthetase (glnA) that decrease glutamine synthetase activity.", "contents": "Mutant strains (nit) of Salmonella typhimurium with a pleiotropic defect in nitrogen metabolism. We have isolated mutant strains (nit) of Salmonella typhimurium that are defective in nitrogen metabolism. They have a reduced ability to use a variety of compounds including glutamate, proline, arginine, N-acetyl-glucosamine, alanine, and adenosine as sole nitrogen source. In addition, although they grow normally on high concentrations of ammonium chloride (greater than 1 mM) as nitrogen source, they grow substantially more slowly than wild type at low concentrations (less than 1 mM). We postulated that the inability of these strains to utilize low concentrations of ammonium chloride accounts for their poor growth on other nitrogen sources. The specific biochemical lesion in strains with a nit mutation is not known; however, mutant strains have no detectable alteration in the activities of glutamine synthetase, glutamate synthetase, or glutamate dehydrogenase, the enzymes known to be involved in assimilation of ammonia. A nit mutation is suppressed by second-site mutations in the structural gene for glutamine synthetase (glnA) that decrease glutamine synthetase activity."}
{"id": "PMID:10276", "title": "Stable, inducible thermoacidophilic alpha-amylase from Bacillus acidocaldarius.", "content": "Bacillus acidocaldarius Agnano 101 produces an inducible thermoacidophilic alpha-amylase. The enzyme production occurs during the stationary phase of growth in the presence of compounds with alpha-1,4-glucosidic linkages. The enzymatic activity is both present in the culture medium and associated with the cells; the enzymes purified from both sources show identical molecular and catalytic properties. The purified amylase has a single polypeptide chain of molecular weight 68,000 and behaves like an alpha-amylase with affinity constants for starch and related substances of 0.8 to 0.9 mg/ml. The pH and temperature optima for activity are 3.5 and 75degreesC, respectively. The amylase is stable at acidic pH (below 4.5). Its thermal stability is strictly dependent upon protein concentration; the half-life at 60degreesC of the amylase in a 70-mug/ml solution is about 5 days.", "contents": "Stable, inducible thermoacidophilic alpha-amylase from Bacillus acidocaldarius. Bacillus acidocaldarius Agnano 101 produces an inducible thermoacidophilic alpha-amylase. The enzyme production occurs during the stationary phase of growth in the presence of compounds with alpha-1,4-glucosidic linkages. The enzymatic activity is both present in the culture medium and associated with the cells; the enzymes purified from both sources show identical molecular and catalytic properties. The purified amylase has a single polypeptide chain of molecular weight 68,000 and behaves like an alpha-amylase with affinity constants for starch and related substances of 0.8 to 0.9 mg/ml. The pH and temperature optima for activity are 3.5 and 75degreesC, respectively. The amylase is stable at acidic pH (below 4.5). Its thermal stability is strictly dependent upon protein concentration; the half-life at 60degreesC of the amylase in a 70-mug/ml solution is about 5 days."}
{"id": "PMID:10277", "title": "Size and transforming activity of deoxyribonucleic acid in Diplococcus pneumoniae during thymidine starvation.", "content": "The transforming activity and the molecular structure of DNA from cells of Diplococcus pneumoniae during thymidine starvation have been analyzed and the effects of thymidine starvation have been compared with the effects of single-strand breaks produced by deoxyribonucleases in DNA of unstarved cells. The decrease in transforming activity of lysates from starved cells as a function of the size of DNA particles, measured by centrifugation in neutral and alkaline sucrose gradients, does not follow the kinetics observed after enzymatic degradation of DNA of unstarved cells. Moreover, a strain lacking exo- and endonuclease activities is not protected from thymineless death. These results suggest that the basic lethal mechanism of thymidine starvation might have an origin other than the activation of nucleases.", "contents": "Size and transforming activity of deoxyribonucleic acid in Diplococcus pneumoniae during thymidine starvation. The transforming activity and the molecular structure of DNA from cells of Diplococcus pneumoniae during thymidine starvation have been analyzed and the effects of thymidine starvation have been compared with the effects of single-strand breaks produced by deoxyribonucleases in DNA of unstarved cells. The decrease in transforming activity of lysates from starved cells as a function of the size of DNA particles, measured by centrifugation in neutral and alkaline sucrose gradients, does not follow the kinetics observed after enzymatic degradation of DNA of unstarved cells. Moreover, a strain lacking exo- and endonuclease activities is not protected from thymineless death. These results suggest that the basic lethal mechanism of thymidine starvation might have an origin other than the activation of nucleases."}
{"id": "PMID:10278", "title": "Carbon and ammonia metabolism of Spirillum lipoferum.", "content": "Intact cells and extracts from Spirillum lipoferum rapidly oxidized malate, succinate, lactate, and pyruvate. Glucose, galactose, fructose, acetate, and citrate did not increase the rate of O2 uptake by cells above the endogenous rate. Cells grown on NH+/4 oxidized the various substrates at about the same rate as did cells grown on N2. Added oxidized nicotinamide adenine dinucleotide generally enhanced O2 uptake by extracts supplied organic acids, whereas oxidized nicotinamide adenine dinucleotide phosphate had little effect. Nitrogenase synthesis repressed by growth of cells in the presence of NH+/4 was derepressed by methionine sulfoximine or methionine sulfone. The total glutamine synthetase activity from N2-grown cells was about eight times that from NH+/4-grown S. lipoferum; the response of glutamate dehydrogenase was the opposite. The total glutamate synthetase activity from N2-grown S. lipoferum was 1.4 to 2.6 times that from NH+/4-grown cells. The levels of poly-beta-hydroxybutyrate and beta-hydroxybutyrate dehydrogenase were elevated in cells grown on N2 as compared with those grown on NH+/4. Cell-free extracts capable of reducing C2H2 have been prepared; both Mg2+ and Mn2+ are required for good activity.", "contents": "Carbon and ammonia metabolism of Spirillum lipoferum. Intact cells and extracts from Spirillum lipoferum rapidly oxidized malate, succinate, lactate, and pyruvate. Glucose, galactose, fructose, acetate, and citrate did not increase the rate of O2 uptake by cells above the endogenous rate. Cells grown on NH+/4 oxidized the various substrates at about the same rate as did cells grown on N2. Added oxidized nicotinamide adenine dinucleotide generally enhanced O2 uptake by extracts supplied organic acids, whereas oxidized nicotinamide adenine dinucleotide phosphate had little effect. Nitrogenase synthesis repressed by growth of cells in the presence of NH+/4 was derepressed by methionine sulfoximine or methionine sulfone. The total glutamine synthetase activity from N2-grown cells was about eight times that from NH+/4-grown S. lipoferum; the response of glutamate dehydrogenase was the opposite. The total glutamate synthetase activity from N2-grown S. lipoferum was 1.4 to 2.6 times that from NH+/4-grown cells. The levels of poly-beta-hydroxybutyrate and beta-hydroxybutyrate dehydrogenase were elevated in cells grown on N2 as compared with those grown on NH+/4. Cell-free extracts capable of reducing C2H2 have been prepared; both Mg2+ and Mn2+ are required for good activity."}
{"id": "PMID:10279", "title": "Photosystem II regulation of macromolecule synthesis in the blue-green alga Aphanocapsa 6714.", "content": "Polymers synthesized by heterotrophically growing (glucose as carbon source)  cultures of Aphanocapsa 6714 were compared with polymers synthesized in photosynthetically grown cultures. Loss of photosystem II by dark incubation, or inhibition of light-grown cells with the photosystem II-specific inhibitor dichlorophenylmethylurea, caused an 80 to 90% reduction in the rate of lipid and total ribonucleic acid synthesis, and more than a 90% reduction in the rate of protein synthesis. In contrast, glycogen synthesis was reduced only about 50% in dark cells and less than 30% in dichlorphenylmethylurea-inhibited cells. After longer heterotrophic growth, glycogen became the major component, whereas in photosynthetically grown cultures protein was the major constituent. 14C (from 14CO2 and/or [14C]glucose) assimilated into protein by heterotrophically grown cells was found in amino acids in nearly the same proportions as in photosynthetically grown cells. Thus, routes of biosynthesis available to autotropic cells were also available to heterotrophic cultures, but the supply of carbon precursors to those pathways was greatly reduced. The limited biosynthesis in heterotrophic cells was not due to a limitation for cellular energy. The adenylates were maintained at nearly the same concentrations (and hence the energy charge also) as in photosynthetic cells. The concentration of reduced nicotinamide adenine dinucleotide phosphate was higher in heterotrophic (dark) cells than in photosynthetic cells. From rates of CO2 fixation and/or glycogen biosynthesis it was determined that stationary-phase cells expended approximately 835, 165, and less than 42 nmol of adenosine 5'-triphosphate per mg (dry weight) of algae per 30 min during photosynthetic, photoheterotrophic, and chemoheterotrophic metabolism, respectively. Analysis of the soluble metabolite pools in dark heterotrophic cultures by double-labeling experiments revealed rapid equilibration of 14C through the monophosphate pools, but much slower movement of label into the diphosphate pools of fructose-1,6-diphosphate and sedoheptulose-1,7-diphosphate. Carbon did flow into 3-phosphoglycerate in the dark; however, the initial rate was low and the concentration of this metabolite soon fell to an undetectable level. In photosynthetic cells, 14C quickly equilibrated throughout all the intermediates of the reductive pentose cycle, in particular, into 3-phosphoglycerate. Analysis of glucose-6-phosphate dehydrogenase in cell extracts showed that the enzyme was very sensitive to product inhibition by reduced nicotinamide adenine dinucleotide.", "contents": "Photosystem II regulation of macromolecule synthesis in the blue-green alga Aphanocapsa 6714. Polymers synthesized by heterotrophically growing (glucose as carbon source)  cultures of Aphanocapsa 6714 were compared with polymers synthesized in photosynthetically grown cultures. Loss of photosystem II by dark incubation, or inhibition of light-grown cells with the photosystem II-specific inhibitor dichlorophenylmethylurea, caused an 80 to 90% reduction in the rate of lipid and total ribonucleic acid synthesis, and more than a 90% reduction in the rate of protein synthesis. In contrast, glycogen synthesis was reduced only about 50% in dark cells and less than 30% in dichlorphenylmethylurea-inhibited cells. After longer heterotrophic growth, glycogen became the major component, whereas in photosynthetically grown cultures protein was the major constituent. 14C (from 14CO2 and/or [14C]glucose) assimilated into protein by heterotrophically grown cells was found in amino acids in nearly the same proportions as in photosynthetically grown cells. Thus, routes of biosynthesis available to autotropic cells were also available to heterotrophic cultures, but the supply of carbon precursors to those pathways was greatly reduced. The limited biosynthesis in heterotrophic cells was not due to a limitation for cellular energy. The adenylates were maintained at nearly the same concentrations (and hence the energy charge also) as in photosynthetic cells. The concentration of reduced nicotinamide adenine dinucleotide phosphate was higher in heterotrophic (dark) cells than in photosynthetic cells. From rates of CO2 fixation and/or glycogen biosynthesis it was determined that stationary-phase cells expended approximately 835, 165, and less than 42 nmol of adenosine 5'-triphosphate per mg (dry weight) of algae per 30 min during photosynthetic, photoheterotrophic, and chemoheterotrophic metabolism, respectively. Analysis of the soluble metabolite pools in dark heterotrophic cultures by double-labeling experiments revealed rapid equilibration of 14C through the monophosphate pools, but much slower movement of label into the diphosphate pools of fructose-1,6-diphosphate and sedoheptulose-1,7-diphosphate. Carbon did flow into 3-phosphoglycerate in the dark; however, the initial rate was low and the concentration of this metabolite soon fell to an undetectable level. In photosynthetic cells, 14C quickly equilibrated throughout all the intermediates of the reductive pentose cycle, in particular, into 3-phosphoglycerate. Analysis of glucose-6-phosphate dehydrogenase in cell extracts showed that the enzyme was very sensitive to product inhibition by reduced nicotinamide adenine dinucleotide."}
{"id": "PMID:10280", "title": "Subunits of the alkaline phosphatase of Bacillus licheniformis: chemical, physicochemical, and dissociation studies.", "content": "The alkaline phosphatase (orthophosphoric monoester phosphydrolase, EC 3.1.3.1) of Bacillus licheniformis MC14 was studied in an attempt to determine the number of subunits contained in the 120,000-molecular-weight native enzyme. Two moles of arginine was liberated per mole of native enzyme by carboxypeptidases A and B in the presence of sodium dodecyl sulfate. The effect on the native enzyme of progressively lowering the solvent buffer pH was monitored by determining the molecular weight by sedimentation equilibrium analysis, the sedimentation coefficient, the frictional coefficient, and the percent alpha-helix content of the enzyme. The alkaline phosphatase dissociates into two subunits around pH 4. At pH 2.8 a further decrease in S value, but no change in molecular weight, is observed, indicating a change in conformation. The frictional coefficients and percent alpha-helix content agree with this interpretation. A subunit molecular weight of 59,000 was calculated from sodium dodecyl sulfate gels.", "contents": "Subunits of the alkaline phosphatase of Bacillus licheniformis: chemical, physicochemical, and dissociation studies. The alkaline phosphatase (orthophosphoric monoester phosphydrolase, EC 3.1.3.1) of Bacillus licheniformis MC14 was studied in an attempt to determine the number of subunits contained in the 120,000-molecular-weight native enzyme. Two moles of arginine was liberated per mole of native enzyme by carboxypeptidases A and B in the presence of sodium dodecyl sulfate. The effect on the native enzyme of progressively lowering the solvent buffer pH was monitored by determining the molecular weight by sedimentation equilibrium analysis, the sedimentation coefficient, the frictional coefficient, and the percent alpha-helix content of the enzyme. The alkaline phosphatase dissociates into two subunits around pH 4. At pH 2.8 a further decrease in S value, but no change in molecular weight, is observed, indicating a change in conformation. The frictional coefficients and percent alpha-helix content agree with this interpretation. A subunit molecular weight of 59,000 was calculated from sodium dodecyl sulfate gels."}
{"id": "PMID:10281", "title": "Inorganic nitrogen assimilation by the photosynthetic bacterium Rhodopseudomonas capsulata.", "content": "The photosynthetic bacterium Rhodopseudomonas capsulata lacks glutamate dehydrogenase and normally uses the glutamine synthetase/glutamate synthase sequence of reactions for assimilation of N2 and ammonia. The glutamine synthetase in cell-free extracts of the organism is completely sedimented by centrifugation at 140,000 X g for 2 h, is inhibited by L-alanine but not by adenosine 5'-monophosphate, and exhibits two apparent Km values for ammonia (ca. 13 muM and 1 mM).", "contents": "Inorganic nitrogen assimilation by the photosynthetic bacterium Rhodopseudomonas capsulata. The photosynthetic bacterium Rhodopseudomonas capsulata lacks glutamate dehydrogenase and normally uses the glutamine synthetase/glutamate synthase sequence of reactions for assimilation of N2 and ammonia. The glutamine synthetase in cell-free extracts of the organism is completely sedimented by centrifugation at 140,000 X g for 2 h, is inhibited by L-alanine but not by adenosine 5'-monophosphate, and exhibits two apparent Km values for ammonia (ca. 13 muM and 1 mM)."}
{"id": "PMID:10282", "title": "Interactions on 3-deoxy and 6-deoxy derivatives of N-acetyl-D-glucosamine with hen lysozyme.", "content": "The interactions of deoxy derivatives of GlcNAc, 6-deoxy-GlcNAc, and 3-deoxy-GlcNAc with hen egg-white lysozyme [EC 3.2.1.17] were studied at various pH's by measuring the changes in the circular dichroic (CD) band at 295 nm. It was shown that 6-deoxy-GlcNAc and 3-deoxy-GlcNAc bind at subsite C of lysozyme and compete with GlcNAc. The pH dependence of the binding constant of 6-deoxy-GlcNAc was the same as that of GlcNAc. On the other hand, the binding constants of 3-deoxy-GlcNAc were 3--10 times smaller than those of GlcNAc in the pH range from 3 to 9. X-ray crystallographic studies show that O(6) and O(3) of GlcNAc at subsite C are hydrogen-bonded to the indole NH's of Trp 62 and Trp 63, respectively, but the above results indicate that Trp 63, not Trp 62, is important for the interaction of GlcNAc with lysozyme.", "contents": "Interactions on 3-deoxy and 6-deoxy derivatives of N-acetyl-D-glucosamine with hen lysozyme. The interactions of deoxy derivatives of GlcNAc, 6-deoxy-GlcNAc, and 3-deoxy-GlcNAc with hen egg-white lysozyme [EC 3.2.1.17] were studied at various pH's by measuring the changes in the circular dichroic (CD) band at 295 nm. It was shown that 6-deoxy-GlcNAc and 3-deoxy-GlcNAc bind at subsite C of lysozyme and compete with GlcNAc. The pH dependence of the binding constant of 6-deoxy-GlcNAc was the same as that of GlcNAc. On the other hand, the binding constants of 3-deoxy-GlcNAc were 3--10 times smaller than those of GlcNAc in the pH range from 3 to 9. X-ray crystallographic studies show that O(6) and O(3) of GlcNAc at subsite C are hydrogen-bonded to the indole NH's of Trp 62 and Trp 63, respectively, but the above results indicate that Trp 63, not Trp 62, is important for the interaction of GlcNAc with lysozyme."}
{"id": "PMID:10283", "title": "Interactions of alpha- and beta-N-acetyl-D-glucosamines with hen and turkey lysozymes.", "content": "The binding constants of alpha- and beta-GlcNAc to hen and turkey lysozymes [EC 3.2.1.17] were determined at various pH's using the method proposed by Ikeda and Hamaguchi (1975) J. Biochem. 77, 1-16). The pH dependence of the binding of beta-GlcNAc to hen lysozyme was essentially the same as that for turkey lysozyme. The pH dependence curves of the binding constants of beta-GlcNAc to hen and turkey lysozymes were interpreted in terms of the participation of Glu 35 (pK 6.0), Asp 52 (pK 3.5), Asp 48 (pK 4.5), and Asp 66 (pK 1.5). The binding constants of alpha-GlcNAc to hen and turkey lysozymes were the same below pH 3.5 but were different above this pH. The main participant residues in the binding of alpha-GlcNAc were Glu 35, Asp 48, and Asp 66 for hen lysozyme and Glu 35 and Asp 66 for turkey lysozyme. The results obtained here were well explained by the following assumptions: (1) above about pH 4, alpha-GlcNAc binds to hen lysozyme in both alpha- and beta-modes, which correspond to the binding orientation of alpha-GlcNAc and that of beta-GlcNAc, respectively, as determined by X-ray crystallographic studies, but it binds predominantly in the beta-mode below about pH 4, (2) beta-GlcNAc binds to hen and turkey lysozymes predominantly in the beta-mode above about pH 4 and in both alpha- and beta-modes below pH 4, and (3) alpha-GlcNAc binds to turkey lysozyme predominantly in the beta-mode over the whole pH range studied.", "contents": "Interactions of alpha- and beta-N-acetyl-D-glucosamines with hen and turkey lysozymes. The binding constants of alpha- and beta-GlcNAc to hen and turkey lysozymes [EC 3.2.1.17] were determined at various pH's using the method proposed by Ikeda and Hamaguchi (1975) J. Biochem. 77, 1-16). The pH dependence of the binding of beta-GlcNAc to hen lysozyme was essentially the same as that for turkey lysozyme. The pH dependence curves of the binding constants of beta-GlcNAc to hen and turkey lysozymes were interpreted in terms of the participation of Glu 35 (pK 6.0), Asp 52 (pK 3.5), Asp 48 (pK 4.5), and Asp 66 (pK 1.5). The binding constants of alpha-GlcNAc to hen and turkey lysozymes were the same below pH 3.5 but were different above this pH. The main participant residues in the binding of alpha-GlcNAc were Glu 35, Asp 48, and Asp 66 for hen lysozyme and Glu 35 and Asp 66 for turkey lysozyme. The results obtained here were well explained by the following assumptions: (1) above about pH 4, alpha-GlcNAc binds to hen lysozyme in both alpha- and beta-modes, which correspond to the binding orientation of alpha-GlcNAc and that of beta-GlcNAc, respectively, as determined by X-ray crystallographic studies, but it binds predominantly in the beta-mode below about pH 4, (2) beta-GlcNAc binds to hen and turkey lysozymes predominantly in the beta-mode above about pH 4 and in both alpha- and beta-modes below pH 4, and (3) alpha-GlcNAc binds to turkey lysozyme predominantly in the beta-mode over the whole pH range studied."}
{"id": "PMID:10284", "title": "Binding of substrate analogs to hen egg-white lysozyme with an ester linkage between Glu 35 and Trp 108.", "content": "The interactions of the substrate analogs beta-methyl-GlcNAc, (GlcNAc)2, and (GlcNAc)3 with hen egg-white lysozyme [EC 3.2.1.17] in which an ester linkage had been formed between Glu 35 and Trp 108 (108 ester lysozyme), were studied by the circular dichroic and fluorescence techniques, and were compared with those for intact lysozyme. The binding constants of beta-methyl-GlcNAc and (GlcNAc)2 to 108 ester lysozyme were essentially the same as those for intact lysozyme in the pH range of 1 to 5. Above pH 5, the binding constants of these saccharides to 108 ester lysozyme did not change with pH, while the binding constants to intact lysozyme decreased. This indicates that Glu 35 (pK 6.0 in intact lysozyme) participates in the binding of these saccharides. The extent and direction of the pK shifts of Asp 52 (pK 3.5), Asp 48 (pK 4.4), and Asp 66 (pK 1.3) observed when beta-methyl-GlcNAc is bound to 108 ester lysozyme were the same as those for intact lysozyme. The participation of Asp 101 and Asp 66 in the binding of (GlcNAc)2 to 108 ester lysozyme was also the same as that for intact lysozyme. These findings indicate that the conformations of subsites B and C are not changed by the formation of the ester linkage. On the other hand, the binding constants of (GlcNAc)3 to 108 ester lysozyme were higher than those for intact lysozyme at all pH values studied. This result is interpreted in terms of an increase in the affinity for a GlcNAc residue of subsite D, which is situated near the esterified Glu 35.", "contents": "Binding of substrate analogs to hen egg-white lysozyme with an ester linkage between Glu 35 and Trp 108. The interactions of the substrate analogs beta-methyl-GlcNAc, (GlcNAc)2, and (GlcNAc)3 with hen egg-white lysozyme [EC 3.2.1.17] in which an ester linkage had been formed between Glu 35 and Trp 108 (108 ester lysozyme), were studied by the circular dichroic and fluorescence techniques, and were compared with those for intact lysozyme. The binding constants of beta-methyl-GlcNAc and (GlcNAc)2 to 108 ester lysozyme were essentially the same as those for intact lysozyme in the pH range of 1 to 5. Above pH 5, the binding constants of these saccharides to 108 ester lysozyme did not change with pH, while the binding constants to intact lysozyme decreased. This indicates that Glu 35 (pK 6.0 in intact lysozyme) participates in the binding of these saccharides. The extent and direction of the pK shifts of Asp 52 (pK 3.5), Asp 48 (pK 4.4), and Asp 66 (pK 1.3) observed when beta-methyl-GlcNAc is bound to 108 ester lysozyme were the same as those for intact lysozyme. The participation of Asp 101 and Asp 66 in the binding of (GlcNAc)2 to 108 ester lysozyme was also the same as that for intact lysozyme. These findings indicate that the conformations of subsites B and C are not changed by the formation of the ester linkage. On the other hand, the binding constants of (GlcNAc)3 to 108 ester lysozyme were higher than those for intact lysozyme at all pH values studied. This result is interpreted in terms of an increase in the affinity for a GlcNAc residue of subsite D, which is situated near the esterified Glu 35."}
{"id": "PMID:10285", "title": "Near-UV circular dichroism of trypsin inhibitor of adzuki beans attributable to disulfide groups.", "content": "The trypsin inhibitor of adzuki (Phaseolus angularis) beans shows a CD spectrum with a negative extremum at 280 nm and a positive shoulder around 245 nm. Since the inhibitor lacks tryptophan and tyrosine, the observed CD spectrum can be attributed to the six disulfide groups in the molecule. The CD features completely disappeared on reduction of the disulfide groups, and converged into a single negative extremum at 270 nm when the groups were modified to form mixed disulfides with glutathione. These observations of the CD properties of the inhibitor strongly suggest the presence  of disulfide groups constrained with respect to their dihedral angles.", "contents": "Near-UV circular dichroism of trypsin inhibitor of adzuki beans attributable to disulfide groups. The trypsin inhibitor of adzuki (Phaseolus angularis) beans shows a CD spectrum with a negative extremum at 280 nm and a positive shoulder around 245 nm. Since the inhibitor lacks tryptophan and tyrosine, the observed CD spectrum can be attributed to the six disulfide groups in the molecule. The CD features completely disappeared on reduction of the disulfide groups, and converged into a single negative extremum at 270 nm when the groups were modified to form mixed disulfides with glutathione. These observations of the CD properties of the inhibitor strongly suggest the presence  of disulfide groups constrained with respect to their dihedral angles."}
{"id": "PMID:10286", "title": "Interaction of diiodo-L-tyrosine and triiodophenol with bovine serum albumin. Circular dichroism and fluorescence studies.", "content": "As a model study to investigate the binding mechanism between thyroid hormones and carrier protein, the interaction of diiodo-L-tyrosine (DIT) and triiodophenol (I3phi) with bovine serum albumin (BSA) was investigated by circular dichroism (CD) and fluorescence methods. In both the DIT-BSA system and the I3phi-BSA system, induced Cotton effect was observed in the wavelength region near 320 nm. This induced Cotton effect was measured at various molar ratios of ligands to BSA (L/P). The value of the ellipticity at 319 nm, [theta]319, in the I3phi-BSA system was remarkably large compared with that of the DIT-BSA system, and [theta]319 at an L/P ratio of one was -1.96 X 10(4) (degree cm2 decimole-1) for the I3phi-BSA system and -0.1 X 10(4) for the DIT-BSA system. The binding constants for the combination of BSA with a single molecule of ligand, calculated by measuring the quenching of the fluorescence of the protein, were 1.33 X 10(5) M(-1) at 15 degrees for the DIT-BSA system and 1.6 X 10(9) M(-1) at 28 degrees for the I3theta-BSA system. These results suggest that the binding of I3theta to BSA is stronger than that of DIT and a cleft may exist more congruent with the molecular dimensions of I3theta than with those of DIT.", "contents": "Interaction of diiodo-L-tyrosine and triiodophenol with bovine serum albumin. Circular dichroism and fluorescence studies. As a model study to investigate the binding mechanism between thyroid hormones and carrier protein, the interaction of diiodo-L-tyrosine (DIT) and triiodophenol (I3phi) with bovine serum albumin (BSA) was investigated by circular dichroism (CD) and fluorescence methods. In both the DIT-BSA system and the I3phi-BSA system, induced Cotton effect was observed in the wavelength region near 320 nm. This induced Cotton effect was measured at various molar ratios of ligands to BSA (L/P). The value of the ellipticity at 319 nm, [theta]319, in the I3phi-BSA system was remarkably large compared with that of the DIT-BSA system, and [theta]319 at an L/P ratio of one was -1.96 X 10(4) (degree cm2 decimole-1) for the I3phi-BSA system and -0.1 X 10(4) for the DIT-BSA system. The binding constants for the combination of BSA with a single molecule of ligand, calculated by measuring the quenching of the fluorescence of the protein, were 1.33 X 10(5) M(-1) at 15 degrees for the DIT-BSA system and 1.6 X 10(9) M(-1) at 28 degrees for the I3theta-BSA system. These results suggest that the binding of I3theta to BSA is stronger than that of DIT and a cleft may exist more congruent with the molecular dimensions of I3theta than with those of DIT."}
{"id": "PMID:10287", "title": "Renal angiotensin I-converting enzyme as a mixture of sialo- and asialo-enzyme, and a rapid purification method.", "content": "Angiotensin I-converting enzyme [EC 3.4.15.1] was rapidly and highly purified from a particulate fraction of hog kidney cortex with 13% yield. The procedure, which was rapid, included fractionation on DEAE-cellulose and calcium phosphate gel, chromatographies on DEAE-Sephadex A-50 and hydroxylapatite columns, and gel filtration on a Sephadex G-200 column. The purified enzyme preparation gave two protein bands on standard disc gel electrophoresis, but showed a single protein component on the gel after treatment with neuraminidase [EC 3.2.1.18]. The data strongly suggest that the purified enzyme preparation was a mixture of sialo- and asialo-enzyme. Sialic acid residues apparently do not contribute to the catalytic activity of the enzyme. The enzyme was activated more by chloride ions than by other halide ions tested, using Bz-Gly-Gly-Gly as a substrate. The dissociation constant for chloride ions was determined to be 2.2 mM. Chloride did not protect the enzyme against heat or low pH. The enzyme was resistant to inactivation by trypsin [EC 3.4.21.4] and chymotrypsin [EC 3.4.21.1].", "contents": "Renal angiotensin I-converting enzyme as a mixture of sialo- and asialo-enzyme, and a rapid purification method. Angiotensin I-converting enzyme [EC 3.4.15.1] was rapidly and highly purified from a particulate fraction of hog kidney cortex with 13% yield. The procedure, which was rapid, included fractionation on DEAE-cellulose and calcium phosphate gel, chromatographies on DEAE-Sephadex A-50 and hydroxylapatite columns, and gel filtration on a Sephadex G-200 column. The purified enzyme preparation gave two protein bands on standard disc gel electrophoresis, but showed a single protein component on the gel after treatment with neuraminidase [EC 3.2.1.18]. The data strongly suggest that the purified enzyme preparation was a mixture of sialo- and asialo-enzyme. Sialic acid residues apparently do not contribute to the catalytic activity of the enzyme. The enzyme was activated more by chloride ions than by other halide ions tested, using Bz-Gly-Gly-Gly as a substrate. The dissociation constant for chloride ions was determined to be 2.2 mM. Chloride did not protect the enzyme against heat or low pH. The enzyme was resistant to inactivation by trypsin [EC 3.4.21.4] and chymotrypsin [EC 3.4.21.1]."}
{"id": "PMID:10288", "title": "Some catalytic and molecular properties of threonine deaminase from Bacillus stearothermophilus.", "content": "Threonine deaminase [EC 4.2.1.16] was highly purified from Bacillus stearothermophilus. The enzyme exhibited maximum activity at 65 degrees and at pH 9.2--9.6. It was inactivated on dilution and on storage at 4 degrees, but was protected by egg albumin. The enzyme was labile at 65 degrees, but became stable in the presence of egg albumin and isoleucine at pH 7.0. The substrate saturation curve for the enzyme reaction at 40 or 65 degrees was hyperbolic, but in the presence of isoleucine, the curve became sigmoidal (n = 2). The enzyme was more sensitive to isoleucine at 40 degrees than at 65 degrees, while valine slightly inhibited the enzyme at both 40 and 65 degrees. Inhibition of the enzyme by isoleucine was antagonized by valine at 40 and 65 degrees. These properties were essentially similar to those of the enzymes from mesophilic and thermophilic bacteria. The enzyme existed in two forms with different molecular sizes, 1.5-5 X 10(6) and 2 X 10(5) daltons, at pH 7.0 and at temperatures below 40 degrees. The larger component disaggregated into the small one at pH 8.5 or above, at temperatures above 50 degrees or in the presence of isoleucine and valine.", "contents": "Some catalytic and molecular properties of threonine deaminase from Bacillus stearothermophilus. Threonine deaminase [EC 4.2.1.16] was highly purified from Bacillus stearothermophilus. The enzyme exhibited maximum activity at 65 degrees and at pH 9.2--9.6. It was inactivated on dilution and on storage at 4 degrees, but was protected by egg albumin. The enzyme was labile at 65 degrees, but became stable in the presence of egg albumin and isoleucine at pH 7.0. The substrate saturation curve for the enzyme reaction at 40 or 65 degrees was hyperbolic, but in the presence of isoleucine, the curve became sigmoidal (n = 2). The enzyme was more sensitive to isoleucine at 40 degrees than at 65 degrees, while valine slightly inhibited the enzyme at both 40 and 65 degrees. Inhibition of the enzyme by isoleucine was antagonized by valine at 40 and 65 degrees. These properties were essentially similar to those of the enzymes from mesophilic and thermophilic bacteria. The enzyme existed in two forms with different molecular sizes, 1.5-5 X 10(6) and 2 X 10(5) daltons, at pH 7.0 and at temperatures below 40 degrees. The larger component disaggregated into the small one at pH 8.5 or above, at temperatures above 50 degrees or in the presence of isoleucine and valine."}
{"id": "PMID:10289", "title": "Temperature-jump studies on the interaction of benzeneboronic acid with chymotrypsinogen.", "content": "The interaction of chymotrypsinogen A with benzeneboronic acid (BBA), a transition state along inhibitor of serine proteases, was investigated by the temperature-jump method using pH indicators. It was found that l/tau is dependent on BBA concentration, in contrast to the case of the alpha-chymotrypsin [EC 3.4.21.1]-BBA system in which l/tau is independent of BBA concentration. By examination of the pH dependences of the kinetic parameters, the acid dissociation behavior of His 57 in chymotrypsinogen, chymotrypsinogen-trigonal BBA complex and chymotrypsinogen-tetrahedral BBA complex was analyzed. The kinetic deuterium isotope effect was also examined and found to occur principally on the acid dissociation constants. The state of the catalytic residues in the zymogen molecule is discussed based on these results.", "contents": "Temperature-jump studies on the interaction of benzeneboronic acid with chymotrypsinogen. The interaction of chymotrypsinogen A with benzeneboronic acid (BBA), a transition state along inhibitor of serine proteases, was investigated by the temperature-jump method using pH indicators. It was found that l/tau is dependent on BBA concentration, in contrast to the case of the alpha-chymotrypsin [EC 3.4.21.1]-BBA system in which l/tau is independent of BBA concentration. By examination of the pH dependences of the kinetic parameters, the acid dissociation behavior of His 57 in chymotrypsinogen, chymotrypsinogen-trigonal BBA complex and chymotrypsinogen-tetrahedral BBA complex was analyzed. The kinetic deuterium isotope effect was also examined and found to occur principally on the acid dissociation constants. The state of the catalytic residues in the zymogen molecule is discussed based on these results."}
{"id": "PMID:10290", "title": "The structure and function of acid proteases. V. Comparative studies on the specific inhibition of acid proteases by diazoacetyl-DL-norleucine methyl ester, 1,2-epoxy-3-(p-nitrophenoxy) propane and pepstatin.", "content": "Comparative studies have been made on the effects of diazoacetyl-DL-norleucine methyl ester (DAN), 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) and pepstatin on acid proteases, including those from Acrocylindrium sp., Aspergillus niger, Aspergillus saitoi, Mucor pusillus, Paecilomyces varioti, Rhizopus chinensis, and Trametes sanguinea, and also porcine pepsin [EC 3.4.23.1] and calf rennin [EC 3.4.23.4] for comparative purposes. These enzymes were rapidly inactivated at similar rates and in 1:1 stiochiometry by reaction with DAN in the presence of cupric ions. The pH profiles of inactivation of these enzymes were similar and had optima at pH 5.5 to 6. They were also inactivated at similar rates by reaction with EPNP, with concomitant incorporation of nearly 2 EPNP molecules per molecule of enzyme. The pH profiles of inactivation were again similar and maximal inactivation was observed at around pH 3 to 4. Some of the EPNP-inactivated enzymes were treated with DAN and shown still to retain reactivity toward DAN. All these enzymes were inhibited strongly by pepstatin, and the reactions of DAN and EPNP with them were also markedly inhibited by prior treatment with pepstatin. These results indicate that the active sites of these enzymes are quite similar and that they presumably have at least two essential carboxyl groups at the active site in common, one reactive with DAN in the presence of cupric ions and the other reactive with EPNP, as has already been demonstrated for porcine pepsin and calf rennin. Pepstatin appears to bind at least part of the active site of each enzyme in a simmilar manner.", "contents": "The structure and function of acid proteases. V. Comparative studies on the specific inhibition of acid proteases by diazoacetyl-DL-norleucine methyl ester, 1,2-epoxy-3-(p-nitrophenoxy) propane and pepstatin. Comparative studies have been made on the effects of diazoacetyl-DL-norleucine methyl ester (DAN), 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) and pepstatin on acid proteases, including those from Acrocylindrium sp., Aspergillus niger, Aspergillus saitoi, Mucor pusillus, Paecilomyces varioti, Rhizopus chinensis, and Trametes sanguinea, and also porcine pepsin [EC 3.4.23.1] and calf rennin [EC 3.4.23.4] for comparative purposes. These enzymes were rapidly inactivated at similar rates and in 1:1 stiochiometry by reaction with DAN in the presence of cupric ions. The pH profiles of inactivation of these enzymes were similar and had optima at pH 5.5 to 6. They were also inactivated at similar rates by reaction with EPNP, with concomitant incorporation of nearly 2 EPNP molecules per molecule of enzyme. The pH profiles of inactivation were again similar and maximal inactivation was observed at around pH 3 to 4. Some of the EPNP-inactivated enzymes were treated with DAN and shown still to retain reactivity toward DAN. All these enzymes were inhibited strongly by pepstatin, and the reactions of DAN and EPNP with them were also markedly inhibited by prior treatment with pepstatin. These results indicate that the active sites of these enzymes are quite similar and that they presumably have at least two essential carboxyl groups at the active site in common, one reactive with DAN in the presence of cupric ions and the other reactive with EPNP, as has already been demonstrated for porcine pepsin and calf rennin. Pepstatin appears to bind at least part of the active site of each enzyme in a simmilar manner."}
{"id": "PMID:10291", "title": "In vitro stimulation by retinol of porcine pancreatic esterase activity toward esters of short-chain fatty acids.", "content": "1. Retinol exerted a remarkable stimulating effect (approx. 260% increase), essentially similar to that (300%) of phytol, on the so-called esterase activity displayed by crude pancreatic lipase [EC 3.1.1.3] toward true solutions of esters, but none of the typical lipase activity toward emulsions of water-insoluble esters. 2. Comparison of the stimulatory effects of retinol derivatives on the esterase activity revealed that retinyl acetate was the most active, being sustantially similar in effect to retinol; retinal was fairly active, while retinoic acid, retinyl palmitate, and beta-ionone were far less active. 3. With various isoprenoid compounds, the efficiency of stimulation increased with the carbon chain length, attaining a maximum at 15 to 20 carbon atoms. Above this chain length the efficiency decreased rapidly. 4. Comparison of the effects of retinol and phytol on the esterase activity of various other lipolytic enzymes indicated that this kind of activator may be relatively specific to porcine pancreatic esterase activity.", "contents": "In vitro stimulation by retinol of porcine pancreatic esterase activity toward esters of short-chain fatty acids. 1. Retinol exerted a remarkable stimulating effect (approx. 260% increase), essentially similar to that (300%) of phytol, on the so-called esterase activity displayed by crude pancreatic lipase [EC 3.1.1.3] toward true solutions of esters, but none of the typical lipase activity toward emulsions of water-insoluble esters. 2. Comparison of the stimulatory effects of retinol derivatives on the esterase activity revealed that retinyl acetate was the most active, being sustantially similar in effect to retinol; retinal was fairly active, while retinoic acid, retinyl palmitate, and beta-ionone were far less active. 3. With various isoprenoid compounds, the efficiency of stimulation increased with the carbon chain length, attaining a maximum at 15 to 20 carbon atoms. Above this chain length the efficiency decreased rapidly. 4. Comparison of the effects of retinol and phytol on the esterase activity of various other lipolytic enzymes indicated that this kind of activator may be relatively specific to porcine pancreatic esterase activity."}
{"id": "PMID:10292", "title": "Cardiac myosin from pig heart ventricle. Purification and enzymatic properties.", "content": "A method is described for the preparation of high purity myosin from the left ventricle of pig heart. The purified myosin was free from nucleic acid, actin, tropomyosin, troponin, the 150,000 molecular weight protein and other contaminants. Analyses of subunits in the purified myosin were carried out on 3.5% acrylamide gel with 0.1% SDS. Of the total protein present in myosin, 11.3% was in the light chains; light chain 1 (LC1), 5.9% and light chain 2 (LC2), 5.4%. Urea gel electrophoresis of the purified myosin showed three closely spaced bands corresponding to the 20,000 dalton, the charge-modified 20,000 dalton and the phosphorylated 20,000 dalton components. The properties of the Ca2+-activated and K+-activated ATPases [EC 3.6.1.3] of the purified myosin were also studied. The Km values were 27 and 55 muM and the Vmax values were 0.263 and 0.317 mumole P1/mg/min for the Ca2+-activated and K+-activated ATPases, respectively. The pH-activity profiles and the effects of SH modification were of the skeletal myosin type except that the activities were lower.", "contents": "Cardiac myosin from pig heart ventricle. Purification and enzymatic properties. A method is described for the preparation of high purity myosin from the left ventricle of pig heart. The purified myosin was free from nucleic acid, actin, tropomyosin, troponin, the 150,000 molecular weight protein and other contaminants. Analyses of subunits in the purified myosin were carried out on 3.5% acrylamide gel with 0.1% SDS. Of the total protein present in myosin, 11.3% was in the light chains; light chain 1 (LC1), 5.9% and light chain 2 (LC2), 5.4%. Urea gel electrophoresis of the purified myosin showed three closely spaced bands corresponding to the 20,000 dalton, the charge-modified 20,000 dalton and the phosphorylated 20,000 dalton components. The properties of the Ca2+-activated and K+-activated ATPases [EC 3.6.1.3] of the purified myosin were also studied. The Km values were 27 and 55 muM and the Vmax values were 0.263 and 0.317 mumole P1/mg/min for the Ca2+-activated and K+-activated ATPases, respectively. The pH-activity profiles and the effects of SH modification were of the skeletal myosin type except that the activities were lower."}
{"id": "PMID:10293", "title": "Inability of the smallest light chain to bind to fetal fast muscle myosin.", "content": "1. The smallest light chain of myosin, g3, was not transferred from adult HMM to fetal myosin in alkali (pH 10.5) under conditions when the light chains dissociated from myosin. 2. The g3 isolated from adult myosin did not bind to fetal myosin at either pH 7.8 or 10.5.", "contents": "Inability of the smallest light chain to bind to fetal fast muscle myosin. 1. The smallest light chain of myosin, g3, was not transferred from adult HMM to fetal myosin in alkali (pH 10.5) under conditions when the light chains dissociated from myosin. 2. The g3 isolated from adult myosin did not bind to fetal myosin at either pH 7.8 or 10.5."}
{"id": "PMID:10294", "title": "Differences in phosphofructokinase regulation in normal and tumor rat thyroid cells.", "content": "The kinetic and molecular properties of a phosphofructokinase derived from a transplantable rat thyroid tumor lacking regulatory control on the glycolytic pathway were studied. The properties of the near-purified enzyme (specific activity 140 units/mg) were compared with those of phosphofructokinase from normal rat thyroid (specific activity 134 units/mg). The electrophoretic mobilities and gel elution behavior of these two enzymes were almost similar. The thyroid tumor phosphofructokinase showed, however, a greater degree of size and/or shape heterogeneity in the presence of ATP than the normal thyroid enzyme, as determined by gel filtration and sucrose density gradient centrifugation. Kinetic studies below pH 7.4 showed a sigmoid response curve for both enzymes when the velocity was determined at 1 mM ATP with varying levels of fructose-6-P. The interaction coefficient, however, was 4.2 and 2.6 for normal and tumor thyroid phosphofructokinase, respectively. Ammonium sulfate decreased the cooperative interactions with the substrate fructose-6-P in both enzymes. The thyroid tumor enzyme, however, was less sensitive to the inhibition by ATP and by citrate. The reversal of citrate inhibition by cyclic 3':5'-adenosine monophosphate was also less effective with the thyroid tumor phosphofructokinase, while the protective effect of fructose-6-P was stronger. The difference in citrate inhibition between tumor and normal thyroid enzyme was not strongly affected by varying the MgCl2 concentration up to 10 mM. It is concluded that the complex allosteric regulation typical of the normal thyroid phosphofructokinase is still present in the enzyme isolated from the thyroid tumor tissue. The latter, however, is more loosely controlled by its physiological effectors, such as ATP, citrate, and cyclic AMP.", "contents": "Differences in phosphofructokinase regulation in normal and tumor rat thyroid cells. The kinetic and molecular properties of a phosphofructokinase derived from a transplantable rat thyroid tumor lacking regulatory control on the glycolytic pathway were studied. The properties of the near-purified enzyme (specific activity 140 units/mg) were compared with those of phosphofructokinase from normal rat thyroid (specific activity 134 units/mg). The electrophoretic mobilities and gel elution behavior of these two enzymes were almost similar. The thyroid tumor phosphofructokinase showed, however, a greater degree of size and/or shape heterogeneity in the presence of ATP than the normal thyroid enzyme, as determined by gel filtration and sucrose density gradient centrifugation. Kinetic studies below pH 7.4 showed a sigmoid response curve for both enzymes when the velocity was determined at 1 mM ATP with varying levels of fructose-6-P. The interaction coefficient, however, was 4.2 and 2.6 for normal and tumor thyroid phosphofructokinase, respectively. Ammonium sulfate decreased the cooperative interactions with the substrate fructose-6-P in both enzymes. The thyroid tumor enzyme, however, was less sensitive to the inhibition by ATP and by citrate. The reversal of citrate inhibition by cyclic 3':5'-adenosine monophosphate was also less effective with the thyroid tumor phosphofructokinase, while the protective effect of fructose-6-P was stronger. The difference in citrate inhibition between tumor and normal thyroid enzyme was not strongly affected by varying the MgCl2 concentration up to 10 mM. It is concluded that the complex allosteric regulation typical of the normal thyroid phosphofructokinase is still present in the enzyme isolated from the thyroid tumor tissue. The latter, however, is more loosely controlled by its physiological effectors, such as ATP, citrate, and cyclic AMP."}
{"id": "PMID:10295", "title": "Partial purification and characterization of a triglyceride lipase from pig adipose tissue.", "content": "A triglyceride lipase was extracted from defatted pig adipose tissue powder with dilute ammonia and purified about 230-fold by a combination of ammonium sulfate fractionation, heparin-Sepharose 4B, DEAE-cellulose, and Sephadex G-150 column chromatographies and isoelectrofocusing electrophoresis. The enzyme was distinguishable in physical and kinetic properties from the two previously defined lipases in adipose tissue, lipoprotein lipase, and hormone-sensitive lipase. The purified enzyme was fully active in the absence of serum lipoprotein and was not stimulated by adenosine 3':5'-monophosphate-dependent protein kinase. In marked contrast to the already defined lipases, the enzyme was strongly inhibited by serum albumin. The enzyme had a molecular weigt of about 43,000, a pI of 5.2, and pH optimum of 7.0. The enzyme hydrolyzed triolein to oleic acid and glycerol, and did not exhibit esterase activity. The apparent Km for triolein was 0.05 mM. Physiological roles of this new species of lipase remained to be explored.", "contents": "Partial purification and characterization of a triglyceride lipase from pig adipose tissue. A triglyceride lipase was extracted from defatted pig adipose tissue powder with dilute ammonia and purified about 230-fold by a combination of ammonium sulfate fractionation, heparin-Sepharose 4B, DEAE-cellulose, and Sephadex G-150 column chromatographies and isoelectrofocusing electrophoresis. The enzyme was distinguishable in physical and kinetic properties from the two previously defined lipases in adipose tissue, lipoprotein lipase, and hormone-sensitive lipase. The purified enzyme was fully active in the absence of serum lipoprotein and was not stimulated by adenosine 3':5'-monophosphate-dependent protein kinase. In marked contrast to the already defined lipases, the enzyme was strongly inhibited by serum albumin. The enzyme had a molecular weigt of about 43,000, a pI of 5.2, and pH optimum of 7.0. The enzyme hydrolyzed triolein to oleic acid and glycerol, and did not exhibit esterase activity. The apparent Km for triolein was 0.05 mM. Physiological roles of this new species of lipase remained to be explored."}
{"id": "PMID:10296", "title": "Compound X. An intermediate in enzymatic halogenation.", "content": "Previous studies have shown that chlorite serves as a halogenation substrate for horseradish peroxidase. In its substrate role, chlorite serves both as a halogen donor and as a source of oxidizing equivalents in the chlorination reaction. We now show that a new spectral intermediate, which we have termed Compound X, can be detected as the initial product of the reaction of chlorite with horseradish peroxidase. The reaction of chlorite with horseradish peroxidase to form Compound X is a relatively fast reaction especially at acidic pH values. The second order rate constant (Kf) for the formation of Compound X at pH 4.5 (optimum pH) is 0.9 X 10(6) M-1 S-1. Compound X, in the absence of a halogen acceptor, decomposes to Compound I and chloride ion. The first order rate constant (Kd) for the decay of Compound X to Compound I is 0.2 s-1 at pH 4.5. The pH optimum for enzymatic chlorination with chlorite compares favorably with the pH profile for the lifetime of Compound X (Kf/Kd). These observations indicate that Compound X is the halogenating intermediate in the chlorite reaction and that the rate of enzymatic chlorination is directly related to the stability of Compound X. We propose an -OCl ligand on a ferric heme as the most likely structure for Compound X.", "contents": "Compound X. An intermediate in enzymatic halogenation. Previous studies have shown that chlorite serves as a halogenation substrate for horseradish peroxidase. In its substrate role, chlorite serves both as a halogen donor and as a source of oxidizing equivalents in the chlorination reaction. We now show that a new spectral intermediate, which we have termed Compound X, can be detected as the initial product of the reaction of chlorite with horseradish peroxidase. The reaction of chlorite with horseradish peroxidase to form Compound X is a relatively fast reaction especially at acidic pH values. The second order rate constant (Kf) for the formation of Compound X at pH 4.5 (optimum pH) is 0.9 X 10(6) M-1 S-1. Compound X, in the absence of a halogen acceptor, decomposes to Compound I and chloride ion. The first order rate constant (Kd) for the decay of Compound X to Compound I is 0.2 s-1 at pH 4.5. The pH optimum for enzymatic chlorination with chlorite compares favorably with the pH profile for the lifetime of Compound X (Kf/Kd). These observations indicate that Compound X is the halogenating intermediate in the chlorite reaction and that the rate of enzymatic chlorination is directly related to the stability of Compound X. We propose an -OCl ligand on a ferric heme as the most likely structure for Compound X."}
{"id": "PMID:10297", "title": "Studies on the regulation of chloroplast NADP-linked glyceraldehyde-3-phosphate dehydrogenase.", "content": "Chloroplast NADP-linked glyceraldehyde-3-phosphate dehydrogenase was resolved into three forms that differed in molecular weight: (a) larger than or equal to 1.5 million; (b) 600,000; and (c) less than or equal to 100,000. After preincubation with an effector (ATP, NADPH, or Pi) the activity of forms a and c was unaffected, whereas the activity of b, the regulatory form, was increased 10-fold. Activation was accompanied by the exposure of previously hidden sulfhydryl groups. The rate of activation was slower than the rate of catalysis and resulted in a lag phase during the measurement of activity when the enzyme was preincubated in the absence of an effector. The addition of one of several compounds as a second effector (at a concentration which itself was nonactivating) in the presence of a first effector enhanced activation by lowering the concentration of the first effector required for half-maximal activation (Pi constant/ATP or NADPH varied; ATP or NADPH constant/Pi varied). Other combinations of effectors caused little change in activity (ATP constant/NADPH varied; NADPH constant/ATP varied). Glyceraldehyde 3-phosphate added as a second effector induced contrasting changes: an increase in the ATP-mediated activation and a decrease in the NADPH-mediated activation. The results are consistent with the view that the products of the photochemical reactions of chloroplasts, ATP, and NADPH, in conjunction with other metabolites, regulate the activity of glyceraldehyde-3-phosphate dehydrogenase in the photosynthetic assimilation of CO2.", "contents": "Studies on the regulation of chloroplast NADP-linked glyceraldehyde-3-phosphate dehydrogenase. Chloroplast NADP-linked glyceraldehyde-3-phosphate dehydrogenase was resolved into three forms that differed in molecular weight: (a) larger than or equal to 1.5 million; (b) 600,000; and (c) less than or equal to 100,000. After preincubation with an effector (ATP, NADPH, or Pi) the activity of forms a and c was unaffected, whereas the activity of b, the regulatory form, was increased 10-fold. Activation was accompanied by the exposure of previously hidden sulfhydryl groups. The rate of activation was slower than the rate of catalysis and resulted in a lag phase during the measurement of activity when the enzyme was preincubated in the absence of an effector. The addition of one of several compounds as a second effector (at a concentration which itself was nonactivating) in the presence of a first effector enhanced activation by lowering the concentration of the first effector required for half-maximal activation (Pi constant/ATP or NADPH varied; ATP or NADPH constant/Pi varied). Other combinations of effectors caused little change in activity (ATP constant/NADPH varied; NADPH constant/ATP varied). Glyceraldehyde 3-phosphate added as a second effector induced contrasting changes: an increase in the ATP-mediated activation and a decrease in the NADPH-mediated activation. The results are consistent with the view that the products of the photochemical reactions of chloroplasts, ATP, and NADPH, in conjunction with other metabolites, regulate the activity of glyceraldehyde-3-phosphate dehydrogenase in the photosynthetic assimilation of CO2."}
{"id": "PMID:10298", "title": "Induction of lipogenesis during differentiation in a \"preadipocyte\" cell line.", "content": "3T3-L1 fibroblasts differentiate in culture into cells having adipocyte character. This transition is accompanied by a 40- to 50-fold  rise in the incorporation of [14C]acetate into triglyceride. The increase in lipogenic rate is exactly parallel to a coordinate rise in the activities of the key enzymes of the fatty acid biosynthetic pathway (ATP-citrate lyase, acetyl-CoA carboxylase, and fatty acid synthetase). Immunological studies indicate that the elevated acetyl-CoA carboxylase activity is the product of an increased cellular enzyme level.", "contents": "Induction of lipogenesis during differentiation in a \"preadipocyte\" cell line. 3T3-L1 fibroblasts differentiate in culture into cells having adipocyte character. This transition is accompanied by a 40- to 50-fold  rise in the incorporation of [14C]acetate into triglyceride. The increase in lipogenic rate is exactly parallel to a coordinate rise in the activities of the key enzymes of the fatty acid biosynthetic pathway (ATP-citrate lyase, acetyl-CoA carboxylase, and fatty acid synthetase). Immunological studies indicate that the elevated acetyl-CoA carboxylase activity is the product of an increased cellular enzyme level."}
{"id": "PMID:10299", "title": "Enzymatic synthesis of biopterin from D-erythrodihydroneopterin triphosphate by extracts of kidneys from Syrian golden hamsters.", "content": "An enzyme system was found in either crude homogenates of dialyzed extracts of liver, kidney, lung, and brain from Syrian golden hamsters that catalyzed the synthesis of radioactive 6(L-erythro-1',2'-dihydroxypropyl)pterin (biopterin) from [U-14C]6(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate (D-erythrolH2neopterin-PPP) preparation. The specific radioactivity of biopterin was found to be comparable to that of D-erythroH2neopterin-PPP. The enzyme system from hamster kidney was purified severalfold by fractionation with ammonium sulfate and with an Ultrogel AcA-34 column. It was demonstrated that (a) NADPH or NADAH was essential and that (b) Mg2+ was stimulatory for the enzymatic synthesis of biopterin from D-erythroH2-NEOPTERIN-PPP. Also GTP and nonphosphorylated neopterins were not converted to biopterin. Although 6-lactyl-7,8-dihydropterin (sepiapterin) was converted to biopterin in the presence of NADPH, sepiapterin was not detected from D-erythroH2neopterin-PPP in the absence of NADPH. A preliminary experiment was performed to identify dihydrobiopterin.", "contents": "Enzymatic synthesis of biopterin from D-erythrodihydroneopterin triphosphate by extracts of kidneys from Syrian golden hamsters. An enzyme system was found in either crude homogenates of dialyzed extracts of liver, kidney, lung, and brain from Syrian golden hamsters that catalyzed the synthesis of radioactive 6(L-erythro-1',2'-dihydroxypropyl)pterin (biopterin) from [U-14C]6(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate (D-erythrolH2neopterin-PPP) preparation. The specific radioactivity of biopterin was found to be comparable to that of D-erythroH2neopterin-PPP. The enzyme system from hamster kidney was purified severalfold by fractionation with ammonium sulfate and with an Ultrogel AcA-34 column. It was demonstrated that (a) NADPH or NADAH was essential and that (b) Mg2+ was stimulatory for the enzymatic synthesis of biopterin from D-erythroH2-NEOPTERIN-PPP. Also GTP and nonphosphorylated neopterins were not converted to biopterin. Although 6-lactyl-7,8-dihydropterin (sepiapterin) was converted to biopterin in the presence of NADPH, sepiapterin was not detected from D-erythroH2neopterin-PPP in the absence of NADPH. A preliminary experiment was performed to identify dihydrobiopterin."}
{"id": "PMID:10300", "title": "Purification and characterization of N-hydroxy-2-acetylaminofluorene sulfotransferase from rat liver.", "content": "N-Hydroxy-2-acetylaminofluorene (N-OH-2-AAF) sulfotransferase is an enzyme that catalyzes the sulfate transfer from the active sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to N-OH-2-AAF to form a highly reactive product acetylaminofluorene N-sulfate. It has been purified about 2000-fold with a yield of over 12% from adult Sprague-Dawley male rat livers by an eight-step procedure. The final preparation was homogeneous on analytrical disc gel electrophoresis. The purified enzyme had activity toward p-nitrophenol with an approximately 1600-fold increase in specific activity over the crude homogenate, but it had almost no detectable activity toward steroids such as estrone, beta-estradiol, testosterone, dehydroisoandrosterone, and corticosterone. There was also very little sulfation activity toward serotonin and L-tyrosine methyl ester. The optimal pH for the enzyme activity is approximately 6.3 when measured in sodium phosphate buffer. Mg2+ at 6 to 9 mM could increase the enzyme activity up to 30%. Mn2+ activated the enzyme only slightly at very low concentrations. Zn2+, Co2+, Cu2+, and Ni2+ were all strongly inhibitory, but Ca2+ had very little effect. Thiol compounds were found to have a stabilizing effect and thiol-blocking reagents were potent inhibitors for this enzyme. The pure enzyme was very unstable especially in diluet solutions. The isoelectric point (pl) of the enzyme is 5.66 +/- 0.07. The molecular weight of the native enzyme was 68,000 +/- 500 as estimated by Sephadex G-100 and G-200 gel filtrations. A single component with molecular weight of 38,250 +/- 1,350 was observed on sodium dodecyl sulfate gel electrophoresis in the absence and presence of 2-mercaptoethanol. Comparison of the enzyme activity in mail and female rat livers at each stage of purification revealed that there was only a trace amount of N-OH-2-AAF sulfotransferase present in the female rat liver.", "contents": "Purification and characterization of N-hydroxy-2-acetylaminofluorene sulfotransferase from rat liver. N-Hydroxy-2-acetylaminofluorene (N-OH-2-AAF) sulfotransferase is an enzyme that catalyzes the sulfate transfer from the active sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to N-OH-2-AAF to form a highly reactive product acetylaminofluorene N-sulfate. It has been purified about 2000-fold with a yield of over 12% from adult Sprague-Dawley male rat livers by an eight-step procedure. The final preparation was homogeneous on analytrical disc gel electrophoresis. The purified enzyme had activity toward p-nitrophenol with an approximately 1600-fold increase in specific activity over the crude homogenate, but it had almost no detectable activity toward steroids such as estrone, beta-estradiol, testosterone, dehydroisoandrosterone, and corticosterone. There was also very little sulfation activity toward serotonin and L-tyrosine methyl ester. The optimal pH for the enzyme activity is approximately 6.3 when measured in sodium phosphate buffer. Mg2+ at 6 to 9 mM could increase the enzyme activity up to 30%. Mn2+ activated the enzyme only slightly at very low concentrations. Zn2+, Co2+, Cu2+, and Ni2+ were all strongly inhibitory, but Ca2+ had very little effect. Thiol compounds were found to have a stabilizing effect and thiol-blocking reagents were potent inhibitors for this enzyme. The pure enzyme was very unstable especially in diluet solutions. The isoelectric point (pl) of the enzyme is 5.66 +/- 0.07. The molecular weight of the native enzyme was 68,000 +/- 500 as estimated by Sephadex G-100 and G-200 gel filtrations. A single component with molecular weight of 38,250 +/- 1,350 was observed on sodium dodecyl sulfate gel electrophoresis in the absence and presence of 2-mercaptoethanol. Comparison of the enzyme activity in mail and female rat livers at each stage of purification revealed that there was only a trace amount of N-OH-2-AAF sulfotransferase present in the female rat liver."}
{"id": "PMID:10301", "title": "Photochemical studies and ultraviolet sensitization of Escherichia coli thymidylate kinase by various halogenated substrate analogs.", "content": "The effect of 5-iodo-2'-deoxyuridine monophosphate (IdUMP), various 5-halogenated-5'-azido-2', 5' -dideoxyuridine derivatives, 2'-deoxy-6-azauridine (AzdUrd), and its halogenated analogs on the ultraviolet sensitization of Escherichia coli thymidylate kinase has been investigated. Only those compounds iodinated in position 5 enhance the rate of ultraviolet inactivation of this enzyme. However, 5'-azido nucleosides with iodo, bromo, chloro, or fluoro substituents in position 5 neither protect nor sensitize thymidylate kinase to ultraviolet inactivation. Thymidine 5'-monophosphate partially protects the enzyme against ultraviolet inactivation either in the presence or absence of ultraviolet-sensitizing iodinated analogs. Magnesium ion does not enhance the ultraviolet inactivation of thymidylate kinase by 5-iodinated nucleoside analogs. The kinatic data support an active site-directed enhancement of the enzyme to ultraviolet inactivation by 5-iodo-2'-deoxyuridine monophosphate, since the concentration of IdUMP required to attain 50% maximal enhancement is 0.24 mM which is in good agreement with its Ki of 0.18 mM. When either [125I]IdUMP or [2-14C]IdUMP was irradiated with the enzyme, both radioactivities were associated with the enzyme, however only with the 14C analog was the amount bound at half-saturation essentially equal to the amount required to inactivate the enzyme by 50%. These data support the hypothesis that the active entity in the enhancement by IdUMP of thymidylate kinase inactivation during ultraviolet irradiation is the uridylate free radical which is formed photochemically from IdUMP. Photochemical studies of 6-azauracil (AzUra), 2'-deoxy-6-azauridine, and 5-iodo-2'-deoxy-6-azauridine (IAzdUrd) were performed. Photolysis of IAzdUrd in the presence of a hydrogen donor yields AzdUrd which upon further photolysis yields the photohydrate. The photohydrate of AzdUrd when incubated in the dark at pH 5.2 is 90% converted back to AzdUrd, whereas the photohydrate of AzUra is only partially (20%) converted to AzUra. The rate of deiodination of IAzdUrd is 2.1-fold greater than that of IdUMP. Although the Ki of IdUMP and IAzdUrd is similar, the increased photosensitivity of the aza analog accounts for the much greater enhancement of ultraviolet inactivation of thymidylate kinase. The ability of a compound to enhance the ultraviolet inactivation of deoxythymidylate kinase is correlated with the potential of the compound to produce a free radical rather than a photohydrate when the enzyme-substrate analog complex is irradiated.", "contents": "Photochemical studies and ultraviolet sensitization of Escherichia coli thymidylate kinase by various halogenated substrate analogs. The effect of 5-iodo-2'-deoxyuridine monophosphate (IdUMP), various 5-halogenated-5'-azido-2', 5' -dideoxyuridine derivatives, 2'-deoxy-6-azauridine (AzdUrd), and its halogenated analogs on the ultraviolet sensitization of Escherichia coli thymidylate kinase has been investigated. Only those compounds iodinated in position 5 enhance the rate of ultraviolet inactivation of this enzyme. However, 5'-azido nucleosides with iodo, bromo, chloro, or fluoro substituents in position 5 neither protect nor sensitize thymidylate kinase to ultraviolet inactivation. Thymidine 5'-monophosphate partially protects the enzyme against ultraviolet inactivation either in the presence or absence of ultraviolet-sensitizing iodinated analogs. Magnesium ion does not enhance the ultraviolet inactivation of thymidylate kinase by 5-iodinated nucleoside analogs. The kinatic data support an active site-directed enhancement of the enzyme to ultraviolet inactivation by 5-iodo-2'-deoxyuridine monophosphate, since the concentration of IdUMP required to attain 50% maximal enhancement is 0.24 mM which is in good agreement with its Ki of 0.18 mM. When either [125I]IdUMP or [2-14C]IdUMP was irradiated with the enzyme, both radioactivities were associated with the enzyme, however only with the 14C analog was the amount bound at half-saturation essentially equal to the amount required to inactivate the enzyme by 50%. These data support the hypothesis that the active entity in the enhancement by IdUMP of thymidylate kinase inactivation during ultraviolet irradiation is the uridylate free radical which is formed photochemically from IdUMP. Photochemical studies of 6-azauracil (AzUra), 2'-deoxy-6-azauridine, and 5-iodo-2'-deoxy-6-azauridine (IAzdUrd) were performed. Photolysis of IAzdUrd in the presence of a hydrogen donor yields AzdUrd which upon further photolysis yields the photohydrate. The photohydrate of AzdUrd when incubated in the dark at pH 5.2 is 90% converted back to AzdUrd, whereas the photohydrate of AzUra is only partially (20%) converted to AzUra. The rate of deiodination of IAzdUrd is 2.1-fold greater than that of IdUMP. Although the Ki of IdUMP and IAzdUrd is similar, the increased photosensitivity of the aza analog accounts for the much greater enhancement of ultraviolet inactivation of thymidylate kinase. The ability of a compound to enhance the ultraviolet inactivation of deoxythymidylate kinase is correlated with the potential of the compound to produce a free radical rather than a photohydrate when the enzyme-substrate analog complex is irradiated."}
{"id": "PMID:10302", "title": "Kinetic studies on the binding affinity of human hemoglobin for the 4th carbon monoxide molecule, L4.", "content": "L4, the affinity of hemoglobin for the 4th CO molecule, has been determined for human adult hemoglobin (HbA) as a function of pH and the presence of organic phosphates by measuring the kinetic parameters for the reaction. l'4, the rate of combination of CO with the triliganded molecule, was measured by flash photolysis while l4, the rate of CO dissociation for the ligand-saturated molecule, was measured by ligand replacement. L4 is pH-dependent and affected by 2,3-diphosphoglycerate. Additionally, this pH dependence of the high affinity state is largely eliminated by carboxypeptidase A digestion. L4 for human fetal hemoglobin (HbF) in phosphate buffers was also determined and found to be pH-dependent. These results cannot be reconciled within the framework of the two-state allosteric model. Additional structures in the conformational equilibrium due to either intermediates in the T to R transition or two or more R states must exist.", "contents": "Kinetic studies on the binding affinity of human hemoglobin for the 4th carbon monoxide molecule, L4. L4, the affinity of hemoglobin for the 4th CO molecule, has been determined for human adult hemoglobin (HbA) as a function of pH and the presence of organic phosphates by measuring the kinetic parameters for the reaction. l'4, the rate of combination of CO with the triliganded molecule, was measured by flash photolysis while l4, the rate of CO dissociation for the ligand-saturated molecule, was measured by ligand replacement. L4 is pH-dependent and affected by 2,3-diphosphoglycerate. Additionally, this pH dependence of the high affinity state is largely eliminated by carboxypeptidase A digestion. L4 for human fetal hemoglobin (HbF) in phosphate buffers was also determined and found to be pH-dependent. These results cannot be reconciled within the framework of the two-state allosteric model. Additional structures in the conformational equilibrium due to either intermediates in the T to R transition or two or more R states must exist."}
{"id": "PMID:10303", "title": "Isolation and partial characterization of monophosphoglycerate mutase from human erythrocytes.", "content": "Monophosphoglycerate mutase has been purified to homogeneity from outdated human erythrocytes as indicated by exclusion chromatography, polyacrylamide gel electrophoresis, and equilibrium centrifugation. Occasionally, the recommended purification procedure yields a small amount (3% or less) of a single extraneous protein which can be deleted from the enzyme preparation by employing an additional purification step. The native enzyme has a molecular weight of 54,000 to 56,000 as determined by equilibrium centrifugation and exclusion chromatography. Disc gel electrophoresis in the presence of sodium dodecyl sulfate yields a single protein band with a molecular weight of 28,600, indicating that the native macromolecule is a dimer composed of subunits of similar mass. Homogeneous monophosphoglycerate mutase is free of diphosphoglycerate mutase, enolase, and nonspecific phosphatase activities; however, the enzyme manifests intrinsic 2,3-diphospho-D-glycerate phosphatase activity as shown by thermal denaturation studies. The diphosphatase activity is stimulated by PPi and glycolate-2-P, but is inhibited by Cl-, HSO3-, and Pi. The pH optimum for both the diphosphatase and the mutase is 6.8. The Km for 2,3-diphospho-D-glycerate in the phosphatase reaction is 82 muM at 37 degrees and pH 7.2. The amino acid composition of homogeneous monophosphoglycerate mutase is given.", "contents": "Isolation and partial characterization of monophosphoglycerate mutase from human erythrocytes. Monophosphoglycerate mutase has been purified to homogeneity from outdated human erythrocytes as indicated by exclusion chromatography, polyacrylamide gel electrophoresis, and equilibrium centrifugation. Occasionally, the recommended purification procedure yields a small amount (3% or less) of a single extraneous protein which can be deleted from the enzyme preparation by employing an additional purification step. The native enzyme has a molecular weight of 54,000 to 56,000 as determined by equilibrium centrifugation and exclusion chromatography. Disc gel electrophoresis in the presence of sodium dodecyl sulfate yields a single protein band with a molecular weight of 28,600, indicating that the native macromolecule is a dimer composed of subunits of similar mass. Homogeneous monophosphoglycerate mutase is free of diphosphoglycerate mutase, enolase, and nonspecific phosphatase activities; however, the enzyme manifests intrinsic 2,3-diphospho-D-glycerate phosphatase activity as shown by thermal denaturation studies. The diphosphatase activity is stimulated by PPi and glycolate-2-P, but is inhibited by Cl-, HSO3-, and Pi. The pH optimum for both the diphosphatase and the mutase is 6.8. The Km for 2,3-diphospho-D-glycerate in the phosphatase reaction is 82 muM at 37 degrees and pH 7.2. The amino acid composition of homogeneous monophosphoglycerate mutase is given."}
{"id": "PMID:10304", "title": "Conversion of proparathyroid hormone to parathyroid hormone by a particulate enzyme of the parathyroid gland.", "content": "The conversion of proparathyroid hormone (proparathormone) to parathyroid hormone (parathormone) by subcellular fractions of the bovine parathyroid has been investigated. The identification of the conversion product as parathormone was established by its elution postion during ion exchange chromatography and gel filtration, and by partial amino acid sequence analysis of its NH2-terminal region. Total homogenates and derived subcellular fractions (600 X g pellet, 5,000 X g pellet, 20,000 X g pellet, 190,000 X g pellet, and 190,000 X g supernatant) all catalyzed the conversion of exogenous [3H]- or [14C]prohormone. Over 60% of the converting activity was in the particulate fractions; the 190,000 X g particulate fraction contained the highest specific converting activity. The converting activity appeared to be an integral component of the membranes since it could only be partially removed by extraction with Triton X-100. The production of parathormone by the particulate converting enzyme increased with time and the concentration of enzyme protein. The optimum pH range was between 7 and 9, and the enzyme was inactive below pH 6. Conversion by the particulate enzyme was inhibited by benzamidine or chloroquine, but not by pancreatic trypsin inhibitor, indicating its dissimilarity to trypsin. When a mixture of [14C]proparathormone and [3H]parathormone was used as substrate, the particulate enzyme did not metabolize the hormone despite over 70% conversion of the prohormone to hormone and other peptides. There was a close correlation between the subcellular distribution of converting activity and that of newly formed parathormone found in the membrane fraction. These data suggest that the particulate converting activity is that concerned with the formation of parathormone in vivo.", "contents": "Conversion of proparathyroid hormone to parathyroid hormone by a particulate enzyme of the parathyroid gland. The conversion of proparathyroid hormone (proparathormone) to parathyroid hormone (parathormone) by subcellular fractions of the bovine parathyroid has been investigated. The identification of the conversion product as parathormone was established by its elution postion during ion exchange chromatography and gel filtration, and by partial amino acid sequence analysis of its NH2-terminal region. Total homogenates and derived subcellular fractions (600 X g pellet, 5,000 X g pellet, 20,000 X g pellet, 190,000 X g pellet, and 190,000 X g supernatant) all catalyzed the conversion of exogenous [3H]- or [14C]prohormone. Over 60% of the converting activity was in the particulate fractions; the 190,000 X g particulate fraction contained the highest specific converting activity. The converting activity appeared to be an integral component of the membranes since it could only be partially removed by extraction with Triton X-100. The production of parathormone by the particulate converting enzyme increased with time and the concentration of enzyme protein. The optimum pH range was between 7 and 9, and the enzyme was inactive below pH 6. Conversion by the particulate enzyme was inhibited by benzamidine or chloroquine, but not by pancreatic trypsin inhibitor, indicating its dissimilarity to trypsin. When a mixture of [14C]proparathormone and [3H]parathormone was used as substrate, the particulate enzyme did not metabolize the hormone despite over 70% conversion of the prohormone to hormone and other peptides. There was a close correlation between the subcellular distribution of converting activity and that of newly formed parathormone found in the membrane fraction. These data suggest that the particulate converting activity is that concerned with the formation of parathormone in vivo."}
{"id": "PMID:10305", "title": "Quantitative aspects of relationship between glucose 6-phosphate transport and hydrolysis for liver microsomal glucose-6-phosphatase system. Selective thermal inactivation of catalytic component in situ at acid pH.", "content": "Studies of the thermal stability of rat liver glucose-6-phosphatase (EC 3.1.3.9) were carried out to further elevate the proposal that the enzymic activity is the result of the coupling of a glucose-6-P-specific translocase and a nonspecific phosphohydrolase-phosphotransferase. Inactivation was observed when micorsomes were incubated at mild temperatures between pH 6.2 and 5.6. The rate of inactivation increased either with increasing hydrogen ion concentration or temperature. However, no inactivation was seen below 15 degrees in media as low as pH 5 or at neutral pH up to 37 degrees. The thermal stability of the enzyme may be controlled by the physical state of the membrane lipids and the degree of protonation of specific residues in the enzyme protein. Microsomes were exposed to inactivating conditions, and kinetic analyses were made of the glucose-6-P phosphohydrolase activities before and after supplementation to 0.4% sodium taurocholate. The results support the postulate and the kinetic characteristics of a given preparation of intact microsomes are determined by the relative capacities of the transport and catalytic components. Before detergent treatment, inactivation (i.e. a decrease in Vmax) was accompanied by a decrease in Km and a reduction in the fraction of latent activity, whereas only Vmax was depressed in disrupted preparations. The possibility that the inactivating treatments caused concurrent disruption of the microsomal membrane was ruled out. It is concluded that exposures to mild heat in acidic media selectively inactivate the catalytic component of the glucose-6-phosphatase system while preserving an intact permeability barrier and a functional glucose-6-P transport system. Analyses of kinetic data obtained in the present and earlier studies revealed several fundamental mathematical relationships among the kinetic constants describing the glucose-6-P phosphohydrolase activities of intact (i.e. the \"system\") and disrupted microsomes (i.e. the catalytic component). The quantitative relationships appear to provide a means to calculate a velocity constant (VT) and a half-saturation constant (KT) for glucose-6-P influx. The well documented, differential responses of the rat liver glucose-6-phosphatase system induced by starvation, experimental diabetes, or cortisol administration were analyzed in terms of these relationships. The possible influences of cisternal inorganic phosphate on the apparent kinetic constants of the intact system are discussed.", "contents": "Quantitative aspects of relationship between glucose 6-phosphate transport and hydrolysis for liver microsomal glucose-6-phosphatase system. Selective thermal inactivation of catalytic component in situ at acid pH. Studies of the thermal stability of rat liver glucose-6-phosphatase (EC 3.1.3.9) were carried out to further elevate the proposal that the enzymic activity is the result of the coupling of a glucose-6-P-specific translocase and a nonspecific phosphohydrolase-phosphotransferase. Inactivation was observed when micorsomes were incubated at mild temperatures between pH 6.2 and 5.6. The rate of inactivation increased either with increasing hydrogen ion concentration or temperature. However, no inactivation was seen below 15 degrees in media as low as pH 5 or at neutral pH up to 37 degrees. The thermal stability of the enzyme may be controlled by the physical state of the membrane lipids and the degree of protonation of specific residues in the enzyme protein. Microsomes were exposed to inactivating conditions, and kinetic analyses were made of the glucose-6-P phosphohydrolase activities before and after supplementation to 0.4% sodium taurocholate. The results support the postulate and the kinetic characteristics of a given preparation of intact microsomes are determined by the relative capacities of the transport and catalytic components. Before detergent treatment, inactivation (i.e. a decrease in Vmax) was accompanied by a decrease in Km and a reduction in the fraction of latent activity, whereas only Vmax was depressed in disrupted preparations. The possibility that the inactivating treatments caused concurrent disruption of the microsomal membrane was ruled out. It is concluded that exposures to mild heat in acidic media selectively inactivate the catalytic component of the glucose-6-phosphatase system while preserving an intact permeability barrier and a functional glucose-6-P transport system. Analyses of kinetic data obtained in the present and earlier studies revealed several fundamental mathematical relationships among the kinetic constants describing the glucose-6-P phosphohydrolase activities of intact (i.e. the \"system\") and disrupted microsomes (i.e. the catalytic component). The quantitative relationships appear to provide a means to calculate a velocity constant (VT) and a half-saturation constant (KT) for glucose-6-P influx. The well documented, differential responses of the rat liver glucose-6-phosphatase system induced by starvation, experimental diabetes, or cortisol administration were analyzed in terms of these relationships. The possible influences of cisternal inorganic phosphate on the apparent kinetic constants of the intact system are discussed."}
{"id": "PMID:10306", "title": "Acid-induced phosphorylation of adenosine 5'-diphosphate bound to coupling factor 1 in spinach chloroplast thylakoids.", "content": "Adenosine 5'-diphosphate, bound to coupling factor 1 (CF1) in spinach chloroplast thylakoids, is in part converted to adenosine 5'-triphosphate, upon injection of the thylakoids into strong acids in the dark. Bound phosphate serves as the phosphoryl donor for this uncoupler-insensitive conversion. Exposure of the thylakoids to heat or to urea prior to their injection into acid caused dissociation of ADP and prevents the apparent acid-induced synthesis of ATP. Conformational changes in CF1 may be elicited by acid denaturation which resemble those brought about by the proton electrochemical gradient across thylakoid membranes.", "contents": "Acid-induced phosphorylation of adenosine 5'-diphosphate bound to coupling factor 1 in spinach chloroplast thylakoids. Adenosine 5'-diphosphate, bound to coupling factor 1 (CF1) in spinach chloroplast thylakoids, is in part converted to adenosine 5'-triphosphate, upon injection of the thylakoids into strong acids in the dark. Bound phosphate serves as the phosphoryl donor for this uncoupler-insensitive conversion. Exposure of the thylakoids to heat or to urea prior to their injection into acid caused dissociation of ADP and prevents the apparent acid-induced synthesis of ATP. Conformational changes in CF1 may be elicited by acid denaturation which resemble those brought about by the proton electrochemical gradient across thylakoid membranes."}
{"id": "PMID:10307", "title": "An in vitro investigation of the anodic polarization and capacitance behavior of 316-L stainless steel.", "content": "Determinations were made of how the corrosion-resistant properties of the passive film on 316-L stainless steel are influenced by the material's mechanical and surface states, and the variable pH and PO2 conditions of the interstitial fluid. Cold-rolled and annealed specimens were surface-prepared, commercially and in the laboratory, respectively, as if for orthopedic implantation. Passive film behavior was studied by the anodic polarization and pulse-potentiostatic capacitance methods. The pH and PO2 of the Ringer's test solution were varied to include interstitial fluid values occurring postoperatively and onto recovery. The anodic polarization behavior of all specimens was found to be pH- and PO2-independent. Breakdown potentials of annealed specimens were 800-950 mV (SCE), in contrast to previously reported values of approximately 350 mV. This substantial increase is related to the influence of surface preparation and, in particular, to the optimization of electropolishing time which acts to produce a microscopically smooth surface, free of debris and disarrayed material. Capacitance behavior of annealed material for potentials greater than 400 mV was consistent with a model involving the entry of chloride and metal ions (mostly Fe) into the passive film. This entry is related to the onset of pitting.", "contents": "An in vitro investigation of the anodic polarization and capacitance behavior of 316-L stainless steel. Determinations were made of how the corrosion-resistant properties of the passive film on 316-L stainless steel are influenced by the material's mechanical and surface states, and the variable pH and PO2 conditions of the interstitial fluid. Cold-rolled and annealed specimens were surface-prepared, commercially and in the laboratory, respectively, as if for orthopedic implantation. Passive film behavior was studied by the anodic polarization and pulse-potentiostatic capacitance methods. The pH and PO2 of the Ringer's test solution were varied to include interstitial fluid values occurring postoperatively and onto recovery. The anodic polarization behavior of all specimens was found to be pH- and PO2-independent. Breakdown potentials of annealed specimens were 800-950 mV (SCE), in contrast to previously reported values of approximately 350 mV. This substantial increase is related to the influence of surface preparation and, in particular, to the optimization of electropolishing time which acts to produce a microscopically smooth surface, free of debris and disarrayed material. Capacitance behavior of annealed material for potentials greater than 400 mV was consistent with a model involving the entry of chloride and metal ions (mostly Fe) into the passive film. This entry is related to the onset of pitting."}
{"id": "PMID:10308", "title": "Secretion of old versus new exportable protein in rat parotid slics. Control by neurotransmitters.", "content": "The possibility that old and new secretory granules do not mix and that older exportable protein can be secreted preferentially was tested on parotid gland in vitro. Slices from fasted animals were pulse labeled for 3 min with L-[3H]leucine. Subcellular fractionstion showed that after 1 90-min chase period, the formation of new labeled secretory granules was mostly completed. The ratio of label in secretory granules to label in microsomes increased 250-fold during the period 5--90 min postpulse. After the 90-min chase, a submaximal rate of secretion was initiated by adding a low concentration of isoproterenol to the slices. Preferential secretion of old unlabeled exportable protein was evident from the finding that the percent of total amylase secreted was 3.5-fold greater than the percent of labeled protein secreted. Preferential secretion of old unlabeled exportable amylase was undiminished even when the chase period before addition of isoproterenol was extended to 240 min. Such long chase incubations were still meaningful due to the fact that the spontaneous rat of amylase release and radioactive protein release from the slices was negligibly low. A high isoproterenol concentration added to the slices after a 90-min chase produced the following results. An initial phase of preferential secretion of old unlabeled protein was soon replaced by secretion of a random mixture of new and old exportable protein. Electron micrographs indicated that high rates of secretion involved sequential fusion of secretory granules so that the lumen extended deep into the cell where the new labeled granules were presumably located. At low rates of secretion, the lumen showed no such deep extensions. Experiments were also conducted on slices from glands which had been largely depleted of old granules by prior injection of isoproterenol into the animals. Secretion of labeled protein from such slices stopped with the export of 80% of the labeled protein. This finding indicates that about 20% of the radioactive protein is cellular nonexportable protein and that the slices are capable of exporting the entire amount of secretory protein which was symthesized in vitrol. In addition to the beta-adrenergic receptor which mediates protein secretion, the parotid acinar cell also possesses an alpha-adrenergic and a cholinergic receptor both of which cause K+ release, vacuole formation, and water secretion. Activation of either of the latter two receptors in conjunction with the beta-adrenergic receptor increased randomization of the protein secreted. It is concluded that in the rat parotid acinar cell there is little spontaneous mixing between old granules near the luminal cell membrane and new granules coming up behind from the Golgi complex. The neurotransmitters which induce secretion produce the observed randomization.", "contents": "Secretion of old versus new exportable protein in rat parotid slics. Control by neurotransmitters. The possibility that old and new secretory granules do not mix and that older exportable protein can be secreted preferentially was tested on parotid gland in vitro. Slices from fasted animals were pulse labeled for 3 min with L-[3H]leucine. Subcellular fractionstion showed that after 1 90-min chase period, the formation of new labeled secretory granules was mostly completed. The ratio of label in secretory granules to label in microsomes increased 250-fold during the period 5--90 min postpulse. After the 90-min chase, a submaximal rate of secretion was initiated by adding a low concentration of isoproterenol to the slices. Preferential secretion of old unlabeled exportable protein was evident from the finding that the percent of total amylase secreted was 3.5-fold greater than the percent of labeled protein secreted. Preferential secretion of old unlabeled exportable amylase was undiminished even when the chase period before addition of isoproterenol was extended to 240 min. Such long chase incubations were still meaningful due to the fact that the spontaneous rat of amylase release and radioactive protein release from the slices was negligibly low. A high isoproterenol concentration added to the slices after a 90-min chase produced the following results. An initial phase of preferential secretion of old unlabeled protein was soon replaced by secretion of a random mixture of new and old exportable protein. Electron micrographs indicated that high rates of secretion involved sequential fusion of secretory granules so that the lumen extended deep into the cell where the new labeled granules were presumably located. At low rates of secretion, the lumen showed no such deep extensions. Experiments were also conducted on slices from glands which had been largely depleted of old granules by prior injection of isoproterenol into the animals. Secretion of labeled protein from such slices stopped with the export of 80% of the labeled protein. This finding indicates that about 20% of the radioactive protein is cellular nonexportable protein and that the slices are capable of exporting the entire amount of secretory protein which was symthesized in vitrol. In addition to the beta-adrenergic receptor which mediates protein secretion, the parotid acinar cell also possesses an alpha-adrenergic and a cholinergic receptor both of which cause K+ release, vacuole formation, and water secretion. Activation of either of the latter two receptors in conjunction with the beta-adrenergic receptor increased randomization of the protein secreted. It is concluded that in the rat parotid acinar cell there is little spontaneous mixing between old granules near the luminal cell membrane and new granules coming up behind from the Golgi complex. The neurotransmitters which induce secretion produce the observed randomization."}
{"id": "PMID:10309", "title": "The microsporidian spore invasion tube. The ultrastructure, isolation, and characterization of the protein comprising the tube.", "content": "The extrusion apparatus of the microsporidian parasitic protozoan Nosema michaelis discharges an invasion (or polar) tube with a velocity suitalbe for piercing cells and injecting infective sporoplasm. The tube is composed of a polar tube protein (PTP) which consists of a single, low molecular weight polypeptide slightly smaller than chymotrypsinogen-A. Assembled PTP tubes resist dissociation in sodium dodecyl sulfate and brief exposures in media at extreme ends of the pH range; however, the tubes are reduced by mercaptoethanol and dithiothreitol. When acidified, mercaptoethanol-reduced PTP self-assembles into plastic, two-dimensional monolayers. Dithiothreitol-reduced PTP will not reassemble when acidified. Evidence is presented which indicates that PTP is assembled as a tube within the spore; that the ejected tube has plasticity during sporoplasm passage; and, finally, that the subunits within the tube polymer are bound together, in part, by interprotein disulfide linkages.", "contents": "The microsporidian spore invasion tube. The ultrastructure, isolation, and characterization of the protein comprising the tube. The extrusion apparatus of the microsporidian parasitic protozoan Nosema michaelis discharges an invasion (or polar) tube with a velocity suitalbe for piercing cells and injecting infective sporoplasm. The tube is composed of a polar tube protein (PTP) which consists of a single, low molecular weight polypeptide slightly smaller than chymotrypsinogen-A. Assembled PTP tubes resist dissociation in sodium dodecyl sulfate and brief exposures in media at extreme ends of the pH range; however, the tubes are reduced by mercaptoethanol and dithiothreitol. When acidified, mercaptoethanol-reduced PTP self-assembles into plastic, two-dimensional monolayers. Dithiothreitol-reduced PTP will not reassemble when acidified. Evidence is presented which indicates that PTP is assembled as a tube within the spore; that the ejected tube has plasticity during sporoplasm passage; and, finally, that the subunits within the tube polymer are bound together, in part, by interprotein disulfide linkages."}
{"id": "PMID:10310", "title": "Adaptive enhancement of amino acid uptake and exodus by thymic lymphocytes: influence of pH.", "content": "Entry of certain free amino acids (alpha aminoisobutyric acid (AIB), alanine and proline), but not of leucine into rat thymic lymphocytes increased progressively when the cells were incubated in amino acid deficient medium. Actinomycin D, cycloheximide, or a high concentration of AIB abolished the time-related increase in AIB accumulation, whereas exposure to a high concentration of leucine had no effect. This phenomenon could not be attributed to a progressive alteration in the nature of the incubation medium nor to reduced transinhibition of AIB uptake. The exodus of AIB also increased with time, but to a smaller degree than AIB entry. Initial rates of AIB entry and exodus increased with increases in the pH of the incubation medium over the range 6.5-8.0. The effects of pH on entry and exodus were time-related, increasing progressively oveb nullified the magnified time related increments in AIB transport caused by prolonged incubation at pH 8.0. The influence of a given pH on transport of AIB decreased rapidly when the cells were transferred to medium of another pH, but this tendency diminished the longer the cells were exposed to the initial pH. pH influenced the entry of alanine and proline in the same fashion as that of AIB, but did not affect leucine entry. These results indicate that thymic lymphocytes exhibit adaptive enhancement in the accumulation of free amino acids that are transported largley by the A or alanine-preferring system, and that the adaptive process involves both entry and exodus. Moreover, alterations in pH modify entry and exodus of these same amino acids, profoundly affect the magnitude of time-released increases, and may induce fundamental changes in the mechanism(s) serving amino acid transport.", "contents": "Adaptive enhancement of amino acid uptake and exodus by thymic lymphocytes: influence of pH. Entry of certain free amino acids (alpha aminoisobutyric acid (AIB), alanine and proline), but not of leucine into rat thymic lymphocytes increased progressively when the cells were incubated in amino acid deficient medium. Actinomycin D, cycloheximide, or a high concentration of AIB abolished the time-related increase in AIB accumulation, whereas exposure to a high concentration of leucine had no effect. This phenomenon could not be attributed to a progressive alteration in the nature of the incubation medium nor to reduced transinhibition of AIB uptake. The exodus of AIB also increased with time, but to a smaller degree than AIB entry. Initial rates of AIB entry and exodus increased with increases in the pH of the incubation medium over the range 6.5-8.0. The effects of pH on entry and exodus were time-related, increasing progressively oveb nullified the magnified time related increments in AIB transport caused by prolonged incubation at pH 8.0. The influence of a given pH on transport of AIB decreased rapidly when the cells were transferred to medium of another pH, but this tendency diminished the longer the cells were exposed to the initial pH. pH influenced the entry of alanine and proline in the same fashion as that of AIB, but did not affect leucine entry. These results indicate that thymic lymphocytes exhibit adaptive enhancement in the accumulation of free amino acids that are transported largley by the A or alanine-preferring system, and that the adaptive process involves both entry and exodus. Moreover, alterations in pH modify entry and exodus of these same amino acids, profoundly affect the magnitude of time-released increases, and may induce fundamental changes in the mechanism(s) serving amino acid transport."}
{"id": "PMID:10311", "title": "Lysosomal hydrolase secretion by Tetrahymena: a comparison of several intralysosomal enzymes with the isoenzymes released into the medium.", "content": "Tetrahymena pyriformis were grown in proteose-peptone medium and then washed and incubated in a dilute salt solution for one hour. The cells were then discarded and the lysosomal hydrolases that had been secreted were subjected to DEAE cellulose column chromatography. At least three isoenzymes of acid phosphatase, three of acid protease, and two of beta-N-acetylhexoseaminidase were found, as well as single peaks of alpha-mannosidase, beta-galactosidase, and beta-fucosidase. The latter two activities were not resolved by the DEAE column and could not be separated in a second chromatographic step on CM-cellulose. Cells were also grown under identical conditions and homogenized in 0.25 M sucrose in order to allow comparison of some of the intracellular lysosomal hydrolases with their secreted counterparts. Two lysosomal populations were resolved by sucrose density gradient sedimentation, a heavy lysosomal fraction, contered at a density of about 1.25 gm/cm3, and a light lysosomal fraction, centered at a density of about 1.16 gm/cm3. These two populations differed in that the light lysosomes did not appear to contain significant amounts of beta-fucosidase, beta-galactosidase, or acid protease, whereas all six of the hydrolase activities studied were present in the heavy lysosomes. The light lysosomal peak occurred in cells grown to transition phase, but was markedly reduced in cells from cultures grown to stationary phase. In addition to these two fractions a third very light particle, containing only alpha-mannosidase activity, was detected just inside the gradient. Measurements were made of the effect of heat (10 minutes at 66 degrees) and of a change in pH from 4.5 (standard assay condition) to 6.0 on the three acid phosphatases and two beta-N-acetylhexoseaminidase isoenzymes resolved by DEAE column chromatography of the secreted hydrolases and on these hydrolyases in the heavy and light lysosomal fractions on the sucrose gradient. Use of the thermostability and pH criteria permitted computation of the expected properties of the intralysosomal acid phosphatase and hexoseaminidase activities if these consisted of the respective isoenzymes in the proportions secreted. It was found that neither the intralysosomal acid phosphatase nor the intralysosomal hexoseaminidase had the properties expected if they consisted of the secreted mixture of the respective isoenzymes, indicating that modification of some of these isoenzymes may have occurred during the 1-hour starvation period or after secretion.", "contents": "Lysosomal hydrolase secretion by Tetrahymena: a comparison of several intralysosomal enzymes with the isoenzymes released into the medium. Tetrahymena pyriformis were grown in proteose-peptone medium and then washed and incubated in a dilute salt solution for one hour. The cells were then discarded and the lysosomal hydrolases that had been secreted were subjected to DEAE cellulose column chromatography. At least three isoenzymes of acid phosphatase, three of acid protease, and two of beta-N-acetylhexoseaminidase were found, as well as single peaks of alpha-mannosidase, beta-galactosidase, and beta-fucosidase. The latter two activities were not resolved by the DEAE column and could not be separated in a second chromatographic step on CM-cellulose. Cells were also grown under identical conditions and homogenized in 0.25 M sucrose in order to allow comparison of some of the intracellular lysosomal hydrolases with their secreted counterparts. Two lysosomal populations were resolved by sucrose density gradient sedimentation, a heavy lysosomal fraction, contered at a density of about 1.25 gm/cm3, and a light lysosomal fraction, centered at a density of about 1.16 gm/cm3. These two populations differed in that the light lysosomes did not appear to contain significant amounts of beta-fucosidase, beta-galactosidase, or acid protease, whereas all six of the hydrolase activities studied were present in the heavy lysosomes. The light lysosomal peak occurred in cells grown to transition phase, but was markedly reduced in cells from cultures grown to stationary phase. In addition to these two fractions a third very light particle, containing only alpha-mannosidase activity, was detected just inside the gradient. Measurements were made of the effect of heat (10 minutes at 66 degrees) and of a change in pH from 4.5 (standard assay condition) to 6.0 on the three acid phosphatases and two beta-N-acetylhexoseaminidase isoenzymes resolved by DEAE column chromatography of the secreted hydrolases and on these hydrolyases in the heavy and light lysosomal fractions on the sucrose gradient. Use of the thermostability and pH criteria permitted computation of the expected properties of the intralysosomal acid phosphatase and hexoseaminidase activities if these consisted of the respective isoenzymes in the proportions secreted. It was found that neither the intralysosomal acid phosphatase nor the intralysosomal hexoseaminidase had the properties expected if they consisted of the secreted mixture of the respective isoenzymes, indicating that modification of some of these isoenzymes may have occurred during the 1-hour starvation period or after secretion."}
{"id": "PMID:10312", "title": "Synthesis of a liver enzyme in hybrid cells.", "content": "Rat hepatoma cells were fused with cells of an established mouse lymphoma line, with normal diploid mouse macrophages, lymphocytes and fibroblasts and with normal diploid rat macrophages and lymphocytes. The liver-specific enzyme tyrosine aminotransferase was produced by almost all the hybrid cells, but usually at a lower level than in the parental hepatoma cells. Most of the hybrids also showed increased levels of this enzyme after exposure to dexamethasone. In the rat x mouse hybrids, the electrophoretic mobility of the enzyme indicated that only the rat hepatoma enzyme was produced. The findings are difficult to explain in terms of simple models involving a single diffusible repressor or activator of tyrosine aminotransferase synthesis.", "contents": "Synthesis of a liver enzyme in hybrid cells. Rat hepatoma cells were fused with cells of an established mouse lymphoma line, with normal diploid mouse macrophages, lymphocytes and fibroblasts and with normal diploid rat macrophages and lymphocytes. The liver-specific enzyme tyrosine aminotransferase was produced by almost all the hybrid cells, but usually at a lower level than in the parental hepatoma cells. Most of the hybrids also showed increased levels of this enzyme after exposure to dexamethasone. In the rat x mouse hybrids, the electrophoretic mobility of the enzyme indicated that only the rat hepatoma enzyme was produced. The findings are difficult to explain in terms of simple models involving a single diffusible repressor or activator of tyrosine aminotransferase synthesis."}
{"id": "PMID:10313", "title": "[Zollinger-Ellison syndrome and parathyroid adenoma. Limits of Wermer's syndrome].", "content": "The authors report the case of a patient with pancreatic and parathyroid adenomatosis and discuss whether it belongs to Wermer's syndrome. After a study of the various possible endocrine involvements, the complexity of hormonal inter-relations is studied, the prognosis and classification of multiple endocrine tumours are then discussed.", "contents": "[Zollinger-Ellison syndrome and parathyroid adenoma. Limits of Wermer's syndrome]. The authors report the case of a patient with pancreatic and parathyroid adenomatosis and discuss whether it belongs to Wermer's syndrome. After a study of the various possible endocrine involvements, the complexity of hormonal inter-relations is studied, the prognosis and classification of multiple endocrine tumours are then discussed."}
{"id": "PMID:10314", "title": "Ion-pair chromatography of acidic drug metabolites and endogenic compounds.", "content": "Liquid-liquid chromatographic systems based on ion-pair partition with silica microparticles as the support for the stationary phase have been used for the separation of anionic compounds of biochemical and pharmacological interest. A high separating efficiency can be obtained with both aqueous and organic mobile phases and the retention is easily regulated by the nature and the concentration of the quaternary ammonium counter ion, present in the aqueous phase. The influence of the composition of the liquid phases on the selectivity and separating efficiency has been studied, as well as equilibration methods and the stability of the systems. Examples are given of separations of sulphonamides, barbiturates, glucuronic and sulphuric acid conjugates of steroidal compounds and phenols glycine conjugates of carboxylic acids (hippuric, nicotinuric and salicyluric acid) and anionic metabolites of biogenic amines (indoleacetic, benzoic, mandelic and phenylacetic acid derivatives).", "contents": "Ion-pair chromatography of acidic drug metabolites and endogenic compounds. Liquid-liquid chromatographic systems based on ion-pair partition with silica microparticles as the support for the stationary phase have been used for the separation of anionic compounds of biochemical and pharmacological interest. A high separating efficiency can be obtained with both aqueous and organic mobile phases and the retention is easily regulated by the nature and the concentration of the quaternary ammonium counter ion, present in the aqueous phase. The influence of the composition of the liquid phases on the selectivity and separating efficiency has been studied, as well as equilibration methods and the stability of the systems. Examples are given of separations of sulphonamides, barbiturates, glucuronic and sulphuric acid conjugates of steroidal compounds and phenols glycine conjugates of carboxylic acids (hippuric, nicotinuric and salicyluric acid) and anionic metabolites of biogenic amines (indoleacetic, benzoic, mandelic and phenylacetic acid derivatives)."}
{"id": "PMID:10315", "title": "Analysis of the acidic fraction of marijuana smoke condensate by capillary gas chromatography-mass spectrometry.", "content": "A method for the analysis of organic acids and phenols isolated from marijuana smoke condensate has been developed. Comparative analyses of standard tobacoo, Mexican, and Turkish marijuana smoke condensates carried out by means of capillary gas chromatography indicated both qualitative and quantitative changes in the constituents of chromatographic profiles. Samples were converted to volatile derivatives by methylation and trimethylsilylation; whereupon, 49 aliphatic acids, aromatic acids, and phenolic compounds were identified by means of capillary gas chromatography-mass spectrometry.", "contents": "Analysis of the acidic fraction of marijuana smoke condensate by capillary gas chromatography-mass spectrometry. A method for the analysis of organic acids and phenols isolated from marijuana smoke condensate has been developed. Comparative analyses of standard tobacoo, Mexican, and Turkish marijuana smoke condensates carried out by means of capillary gas chromatography indicated both qualitative and quantitative changes in the constituents of chromatographic profiles. Samples were converted to volatile derivatives by methylation and trimethylsilylation; whereupon, 49 aliphatic acids, aromatic acids, and phenolic compounds were identified by means of capillary gas chromatography-mass spectrometry."}
{"id": "PMID:10316", "title": "Electron capture and multiple ion detection of benzodiazepine esters in pharmacokinetic studies.", "content": "A sensitive and highly specific gas-liquid chromatographic method is described for the determination of benzodiazepine esters. The method involves the extraction of pivoxazepam and 2'-chloropivoxazepam from blood and urine samples and the hydrolysis of both drugs with strong acid to the corresponding 2-amino-5-chlorobenzophenone (ACB) and 2-amino-5,2'-dichlorobenzophenone (ACDB). Recoveries of 97-98% have been obtained and the trifluoroacetic (TFA) derivatives of both benzophenones (ACB-TFA and ACDB-TFA) can be chromatographed on OV-17, in a short time, with good electron-capture detector (ECD) responses. The mass spectra of these derivatives provide abundant molecular ions suitable for mass spectrometric detection by multiple ion detection (MID),  with a considerable improvement in specificity compared with the ECD responses. The detection limits in blood specimens have been established at 5-10 ng/ml by ECD and 0.5-0.8 ng/ml by MID. The method has been applied to the study of blood levels attained after i.v. and oral doses in rats and in man.", "contents": "Electron capture and multiple ion detection of benzodiazepine esters in pharmacokinetic studies. A sensitive and highly specific gas-liquid chromatographic method is described for the determination of benzodiazepine esters. The method involves the extraction of pivoxazepam and 2'-chloropivoxazepam from blood and urine samples and the hydrolysis of both drugs with strong acid to the corresponding 2-amino-5-chlorobenzophenone (ACB) and 2-amino-5,2'-dichlorobenzophenone (ACDB). Recoveries of 97-98% have been obtained and the trifluoroacetic (TFA) derivatives of both benzophenones (ACB-TFA and ACDB-TFA) can be chromatographed on OV-17, in a short time, with good electron-capture detector (ECD) responses. The mass spectra of these derivatives provide abundant molecular ions suitable for mass spectrometric detection by multiple ion detection (MID),  with a considerable improvement in specificity compared with the ECD responses. The detection limits in blood specimens have been established at 5-10 ng/ml by ECD and 0.5-0.8 ng/ml by MID. The method has been applied to the study of blood levels attained after i.v. and oral doses in rats and in man."}
{"id": "PMID:10317", "title": "Characterization of bacteroides melaninogenicus.", "content": "Fifty-eight human isolates of Bacteroides melaninogenicus, 42 from a variety of clinical infections and the rest from normal flora, were studied for pigment production and ultraviolet light fluorescence and by forty biochemical and other tests, including end-product analysis by gas-liquid chromatography. In a number of instances, tests were repeated several times and the results were reproducible. Agar plate dilution susceptibility tests were also performed to 12 antimicrobial agents. These 58 strains could be reliably placed into three groups, corresponding to the three subspecies described, based on seven characteristics. These included acid production in peptone-yeast-glucose medium, production of n-butyric acid from peptone-yeast-glucose medium, esculin hydrolysis, starch hydrolysis, indole production, effect on milk, and lipase production. Production of hydrogen gas in peptone-yeast-fructose medium may be another distinguishing characteristic. In general there was not much difference in the susceptibility of the three groups to the various antimicrobial agents tested. Two strains had a minimal inhibitory concentration of penicillin G of 16 and 32 U/ml, respectively. Three strains did not produce a black pigment in spite of prolonged incubation on blood-containing media.", "contents": "Characterization of bacteroides melaninogenicus. Fifty-eight human isolates of Bacteroides melaninogenicus, 42 from a variety of clinical infections and the rest from normal flora, were studied for pigment production and ultraviolet light fluorescence and by forty biochemical and other tests, including end-product analysis by gas-liquid chromatography. In a number of instances, tests were repeated several times and the results were reproducible. Agar plate dilution susceptibility tests were also performed to 12 antimicrobial agents. These 58 strains could be reliably placed into three groups, corresponding to the three subspecies described, based on seven characteristics. These included acid production in peptone-yeast-glucose medium, production of n-butyric acid from peptone-yeast-glucose medium, esculin hydrolysis, starch hydrolysis, indole production, effect on milk, and lipase production. Production of hydrogen gas in peptone-yeast-fructose medium may be another distinguishing characteristic. In general there was not much difference in the susceptibility of the three groups to the various antimicrobial agents tested. Two strains had a minimal inhibitory concentration of penicillin G of 16 and 32 U/ml, respectively. Three strains did not produce a black pigment in spite of prolonged incubation on blood-containing media."}
{"id": "PMID:10318", "title": "Recent rural health research.", "content": "Recent rural health research may be examined in two ways: needs and solutions. A definition of needs requires an evaluation of the social factors that affect the expectations and the behavior of both the provider and the consumer. Three types of solutions should be considered: the appropriate utilization of manpower, including the efforts to influence physician location and specialty distribution, new health practitioners, and team approaches; the new technology for transportation and communication; and the organization of new delivery systems. Two areas of rural health research that need more attention are program evaluation and financial planning.", "contents": "Recent rural health research. Recent rural health research may be examined in two ways: needs and solutions. A definition of needs requires an evaluation of the social factors that affect the expectations and the behavior of both the provider and the consumer. Three types of solutions should be considered: the appropriate utilization of manpower, including the efforts to influence physician location and specialty distribution, new health practitioners, and team approaches; the new technology for transportation and communication; and the organization of new delivery systems. Two areas of rural health research that need more attention are program evaluation and financial planning."}
{"id": "PMID:10331", "title": "Mouse ovarian alkaline phosphatase activities that respond to gonadotropins: histochemical and biochemical studies.", "content": "Alkaline phosphatase activity was measured in whole ovarian homogenates from pre-pubertal mice of different ages, with and without prior injection of human chorionic gonadotropin. Alkaline phosphatase activity was also scored in the different cell types in sections of similar ovaries, using two distinct histochemical procedures. The results from those methods differed. Biochemical studies indicated the presence of three distinct alakaline phosphatase activities: I and Ib, both optimal at pH 10.4 and with similar substrate requirements and inhibitor sensitivities (phosphatase I being characteristic of unstimulated ovaries and Ib of ovaries stimulated with human luteinizing hormone or human chorionic gonadotropin), and phosphatase II, optimal at pH 9.4, with different substrate requirements and inhibitor sensitivities. The differences observed using the histochemical procedures can probably be accounted for by the effects of different incubation conditions on the activities of these three enzymes.", "contents": "Mouse ovarian alkaline phosphatase activities that respond to gonadotropins: histochemical and biochemical studies. Alkaline phosphatase activity was measured in whole ovarian homogenates from pre-pubertal mice of different ages, with and without prior injection of human chorionic gonadotropin. Alkaline phosphatase activity was also scored in the different cell types in sections of similar ovaries, using two distinct histochemical procedures. The results from those methods differed. Biochemical studies indicated the presence of three distinct alakaline phosphatase activities: I and Ib, both optimal at pH 10.4 and with similar substrate requirements and inhibitor sensitivities (phosphatase I being characteristic of unstimulated ovaries and Ib of ovaries stimulated with human luteinizing hormone or human chorionic gonadotropin), and phosphatase II, optimal at pH 9.4, with different substrate requirements and inhibitor sensitivities. The differences observed using the histochemical procedures can probably be accounted for by the effects of different incubation conditions on the activities of these three enzymes."}
{"id": "PMID:10332", "title": "The occurrence of salmonellas, mycobacteria and pathogenic strains of Escherichia coli in pig slurry.", "content": "Ninety-eight samples of pig slurry from 54 farms were examined for the presence of salmonellas, porcine enteropathogenic strains of haemolytic Escherichia coli and mycobacteria. Salmonellas were isolated from 12 farms (22%) and enteropathogenic E. coli from 13 farms (24%). Pathogenic mycobacteria were not isolated. Salmonellas were isolated from 7 of 16 farms (44%) stocked with 'minimal disease' pigs compared with only 5 of 38 farms (13%) stocked with conventionally reared pigs. Conversely enteropathogenic coliforms were isolated from 3 of 16 farms (19%) stocked with 'minimal disease' pigs compared with 10 of 38 farms (26%) stocked with conventionally reared pigs.", "contents": "The occurrence of salmonellas, mycobacteria and pathogenic strains of Escherichia coli in pig slurry. Ninety-eight samples of pig slurry from 54 farms were examined for the presence of salmonellas, porcine enteropathogenic strains of haemolytic Escherichia coli and mycobacteria. Salmonellas were isolated from 12 farms (22%) and enteropathogenic E. coli from 13 farms (24%). Pathogenic mycobacteria were not isolated. Salmonellas were isolated from 7 of 16 farms (44%) stocked with 'minimal disease' pigs compared with only 5 of 38 farms (13%) stocked with conventionally reared pigs. Conversely enteropathogenic coliforms were isolated from 3 of 16 farms (19%) stocked with 'minimal disease' pigs compared with 10 of 38 farms (26%) stocked with conventionally reared pigs."}
{"id": "PMID:10333", "title": "Detection of serum proteins in the electrophoretic patterns of total proteins of mycoplasma cells.", "content": "The contamination of mycoplasma cell preparations by serum proteins originating from culture medium was studied. A. laidlawii and M. arthritidis cells were grown in the presence of [14C]-aminoacids, and the cells were washed with 0-9% NaC1 by threefold centrifugation. Total proteins of the washed cells were analysed by SDS gel electrophoresis. Coomassie-stained electrophoretic patterns were compared with autoradiographs of the same gels. The stained electrophoretic pattern of washed A. laidlawii grown without serum was identical with autoradiographs of the same cells grown without or with serum. That of washed A. laidlawii grown with serum differed from the corresponding autoradiography by the presence of extra protein bands I, II, III, and IV with molecular weights of over 160,000, 80,000-87,000, 55,000 and 25,000, respectively. The same extra bands were found in stained electrophoretic patterns of washed: (a) A. laidlawii cells grown without serum and mixed with serum in the stationary phase, (b) M. arthritidis cells, as compared with their autoradiographs, (c) serum precipitate. The bands III and IV may be due to the heavy and light chains of gamma-globulin, the band II might belong to transferrin or to some component of complement. Acidification of serum to pH 5 brought about 100-fold rise of amount of serum precipitate, the number of bands in the electrophoretic pattern of the precipitate being also increased. Stained electrophoretic patterns of cells purified by twofold centrifugation in step sucrose density gradient (1-20-1-27 g./cm.3 for A. laidlawii, and 1-15-1-25 for M. arthritidis) contained no extra bands and matched completely with their autoradiographs. It was concluded that contamination of washed mycoplasma cells by serum proteins is mainly due to co-precipitation of aggregated serum proteins together with cells during centrifugation rather than to adsorption of serum proteins on the cell surface.", "contents": "Detection of serum proteins in the electrophoretic patterns of total proteins of mycoplasma cells. The contamination of mycoplasma cell preparations by serum proteins originating from culture medium was studied. A. laidlawii and M. arthritidis cells were grown in the presence of [14C]-aminoacids, and the cells were washed with 0-9% NaC1 by threefold centrifugation. Total proteins of the washed cells were analysed by SDS gel electrophoresis. Coomassie-stained electrophoretic patterns were compared with autoradiographs of the same gels. The stained electrophoretic pattern of washed A. laidlawii grown without serum was identical with autoradiographs of the same cells grown without or with serum. That of washed A. laidlawii grown with serum differed from the corresponding autoradiography by the presence of extra protein bands I, II, III, and IV with molecular weights of over 160,000, 80,000-87,000, 55,000 and 25,000, respectively. The same extra bands were found in stained electrophoretic patterns of washed: (a) A. laidlawii cells grown without serum and mixed with serum in the stationary phase, (b) M. arthritidis cells, as compared with their autoradiographs, (c) serum precipitate. The bands III and IV may be due to the heavy and light chains of gamma-globulin, the band II might belong to transferrin or to some component of complement. Acidification of serum to pH 5 brought about 100-fold rise of amount of serum precipitate, the number of bands in the electrophoretic pattern of the precipitate being also increased. Stained electrophoretic patterns of cells purified by twofold centrifugation in step sucrose density gradient (1-20-1-27 g./cm.3 for A. laidlawii, and 1-15-1-25 for M. arthritidis) contained no extra bands and matched completely with their autoradiographs. It was concluded that contamination of washed mycoplasma cells by serum proteins is mainly due to co-precipitation of aggregated serum proteins together with cells during centrifugation rather than to adsorption of serum proteins on the cell surface."}
{"id": "PMID:10334", "title": "Comparison of the inactivation of IgM and IgG complement fixation sites by acid and base.", "content": "Rabbit IgM antibodies to denatured mammalian or T6 bacteriophage DNA or poly(A)-poly(U) irreversibly lost complement-(C) fixation reactivity on exposure to low pH and reneutralization, with a halving of the complement-fixation titer occurring after treatment at about pH 3. The titers of IgG antibodies to denatured phage DNA, to poly(A)-poly(U), or to hemocyanin were halved only after exposure to pH 2. Inactivation by acid was enhanced by low protein concentrations, incubation at higher temperatures, and by slow reneutralization; under all these conditions it was more extensive with IgM than with IgG. Inactivation of IgM C-fixation activity at pH 2.5 and room temperature was a first order reaction, with a half-time of about 20 min. Both classes retained antigen-binding activity after exposure to pH 2. In the alkaline range, full C-fixation reactivity was retained by both classes after reneutralization from pH 11.5, some loss occurred at pH 12, and total irreversible inactivation occurred by pH 12.5. In the latter case, antigen-binding activity was also lost. The C-fixation inactivation curves in the alkaline range were similar for IgG and IgM antibodies.", "contents": "Comparison of the inactivation of IgM and IgG complement fixation sites by acid and base. Rabbit IgM antibodies to denatured mammalian or T6 bacteriophage DNA or poly(A)-poly(U) irreversibly lost complement-(C) fixation reactivity on exposure to low pH and reneutralization, with a halving of the complement-fixation titer occurring after treatment at about pH 3. The titers of IgG antibodies to denatured phage DNA, to poly(A)-poly(U), or to hemocyanin were halved only after exposure to pH 2. Inactivation by acid was enhanced by low protein concentrations, incubation at higher temperatures, and by slow reneutralization; under all these conditions it was more extensive with IgM than with IgG. Inactivation of IgM C-fixation activity at pH 2.5 and room temperature was a first order reaction, with a half-time of about 20 min. Both classes retained antigen-binding activity after exposure to pH 2. In the alkaline range, full C-fixation reactivity was retained by both classes after reneutralization from pH 11.5, some loss occurred at pH 12, and total irreversible inactivation occurred by pH 12.5. In the latter case, antigen-binding activity was also lost. The C-fixation inactivation curves in the alkaline range were similar for IgG and IgM antibodies."}
{"id": "PMID:10335", "title": "Genetic control of the antibody response to type III pneumococcal polysaccharide in mice. III. Analysis of genes governing the expression of regulatory T cell activity.", "content": "Recombinant-inbred strains of mice, as well as the progenitor strains from which they were derived, were evaluated with respect to the capacity of B cells to respond to an optimally immunogenic dose of Type III pneumococcal polysaccharide (SSS-III) and the amount of suppressor and amplifier T cell activity present. None of these functional activities was found to be linked to genes within the major histocompatibility (H-2) or the IgCH allotype complex, and several autosomal genes appeared to govern the expression of each of these characteristics.", "contents": "Genetic control of the antibody response to type III pneumococcal polysaccharide in mice. III. Analysis of genes governing the expression of regulatory T cell activity. Recombinant-inbred strains of mice, as well as the progenitor strains from which they were derived, were evaluated with respect to the capacity of B cells to respond to an optimally immunogenic dose of Type III pneumococcal polysaccharide (SSS-III) and the amount of suppressor and amplifier T cell activity present. None of these functional activities was found to be linked to genes within the major histocompatibility (H-2) or the IgCH allotype complex, and several autosomal genes appeared to govern the expression of each of these characteristics."}
{"id": "PMID:10336", "title": "Bacterial interference by oropharynegeal and clinical isolates of anaerobic bacteria.", "content": "Anaerobic isolates were tested for bacterial inhibitory activity. Of 144 isolates, 102 were from oropharynegeal washings, and 42 were from clinical specimens. Thirteen facultative bacterial species (seven members of the Enterobacteriaceae and six species of gram-positive cocci) were used as indicators of inhibition. Eleven anaerobic species were isolated from oral secretions. All isolates of Bacteroides melaninogenicus, the most commonly recovered species, consistently inhibited several species of indicator bacteria. Bacteroides fragilis, Bacteroides oralis, and Peptostreptococcus anaerobius had unprecictable inhibitory activity, whereas most of the other oral anaerobes were noninhibitory. The 42 clinical species were generally noninhibitory.", "contents": "Bacterial interference by oropharynegeal and clinical isolates of anaerobic bacteria. Anaerobic isolates were tested for bacterial inhibitory activity. Of 144 isolates, 102 were from oropharynegeal washings, and 42 were from clinical specimens. Thirteen facultative bacterial species (seven members of the Enterobacteriaceae and six species of gram-positive cocci) were used as indicators of inhibition. Eleven anaerobic species were isolated from oral secretions. All isolates of Bacteroides melaninogenicus, the most commonly recovered species, consistently inhibited several species of indicator bacteria. Bacteroides fragilis, Bacteroides oralis, and Peptostreptococcus anaerobius had unprecictable inhibitory activity, whereas most of the other oral anaerobes were noninhibitory. The 42 clinical species were generally noninhibitory."}
{"id": "PMID:10338", "title": "Inhibition of pituitary prolactin secretion by human placental lactogen in rats.", "content": "Intact female rats given twice daily injections of 1 mg human placental lactogen (HPL) showed continued dioestrous vaginal smears and their ovarian corpora lutea were found to be hypertrophied and functiona. The serum prolactin level was significantly lower in these rats than in the controls at dioestrus as well as at pro-oestrus. Twice-daily injections of 0.5 or 2 mg HPL to ovariectomized rats decreased serum and pituitary levels of prolactin and increased hypothalamic activity of prolactin inhibiting hormone, although the effect was less at the lower dose. Human placental lactogen had no direct effect on pituitary prolactin secretion in vitro. These findings have demonstrated that HPL, like prolactin itself, inhibits prolactin secretion by actin", "contents": "Inhibition of pituitary prolactin secretion by human placental lactogen in rats. Intact female rats given twice daily injections of 1 mg human placental lactogen (HPL) showed continued dioestrous vaginal smears and their ovarian corpora lutea were found to be hypertrophied and functiona. The serum prolactin level was significantly lower in these rats than in the controls at dioestrus as well as at pro-oestrus. Twice-daily injections of 0.5 or 2 mg HPL to ovariectomized rats decreased serum and pituitary levels of prolactin and increased hypothalamic activity of prolactin inhibiting hormone, although the effect was less at the lower dose. Human placental lactogen had no direct effect on pituitary prolactin secretion in vitro. These findings have demonstrated that HPL, like prolactin itself, inhibits prolactin secretion by actin"}
{"id": "PMID:10339", "title": "A comparison of the cholinesterases of an oyster (Crassostrea virginica) and a clam (Macrocallista nimbosa).", "content": "Cholinesterase activities in the hearts and ganglia of an oyster (Crassostrea virginica) and a venerid clam (Macrocallista nimbosa) were measured and compared. Tissue extracts were partially purified by ammonium sulfate fractionation followed by gel column chromatography. Enzymatic activity was assayed spectrophotometrically; substrates were acetyl-, butyryl-, and propionylthiocholine (ATC, BTC, PTC). Kinetic constants characterizing each enzyme were derived. At all substrate concentrations, the hydrolysis rates of both clam enzymes were in the order: BTC greater than PTC greater than ATC. With oyster enzymes the ranking was ATC greater than or equal to PTC greater BTC. The specific activities of oyster heart and ganglion enzymes were similar. In contrast, clam ganglion extracts were 75-100 times more active than clam heart extracts and, with any substrate, had greater activity than either oyster enzyme. All enzyme preparations proved to be homogeneous on the bases of constant substrate activity ratios in successive column fractions, and of intermediate velocities with mixed substrates. Six cholinesterase inhibitors were tested. The specific acetylcholinesterase antagonist, B.W. 62C47, WAS MUCH MORE EFFECTIVE AGAINST OYSTER ENZYMES, WHILE THE SPECIFIC ANTIBUTYRYLCHOLINESTERASE, ISO-OMPA, almost totally inhibited calm enzyme activity, but had little effect on oyster. Eserine was the most effective inhibitor of both enzymes. In conclusion, the enzymes in oyster tissues are acetylcholinesterases, while clam enzymes are butyrylcholinesterases. Nevertheless, clam ganglion esterase is sifficiently active to hydrolyze the physiological substrate, acetylcholine. These results explain the long-observed differences in isolated heart pharmacology between ostreid and venerid bivalves.", "contents": "A comparison of the cholinesterases of an oyster (Crassostrea virginica) and a clam (Macrocallista nimbosa). Cholinesterase activities in the hearts and ganglia of an oyster (Crassostrea virginica) and a venerid clam (Macrocallista nimbosa) were measured and compared. Tissue extracts were partially purified by ammonium sulfate fractionation followed by gel column chromatography. Enzymatic activity was assayed spectrophotometrically; substrates were acetyl-, butyryl-, and propionylthiocholine (ATC, BTC, PTC). Kinetic constants characterizing each enzyme were derived. At all substrate concentrations, the hydrolysis rates of both clam enzymes were in the order: BTC greater than PTC greater than ATC. With oyster enzymes the ranking was ATC greater than or equal to PTC greater BTC. The specific activities of oyster heart and ganglion enzymes were similar. In contrast, clam ganglion extracts were 75-100 times more active than clam heart extracts and, with any substrate, had greater activity than either oyster enzyme. All enzyme preparations proved to be homogeneous on the bases of constant substrate activity ratios in successive column fractions, and of intermediate velocities with mixed substrates. Six cholinesterase inhibitors were tested. The specific acetylcholinesterase antagonist, B.W. 62C47, WAS MUCH MORE EFFECTIVE AGAINST OYSTER ENZYMES, WHILE THE SPECIFIC ANTIBUTYRYLCHOLINESTERASE, ISO-OMPA, almost totally inhibited calm enzyme activity, but had little effect on oyster. Eserine was the most effective inhibitor of both enzymes. In conclusion, the enzymes in oyster tissues are acetylcholinesterases, while clam enzymes are butyrylcholinesterases. Nevertheless, clam ganglion esterase is sifficiently active to hydrolyze the physiological substrate, acetylcholine. These results explain the long-observed differences in isolated heart pharmacology between ostreid and venerid bivalves."}
{"id": "PMID:10343", "title": "Factors affecting the uptake and metabolism of soluble carbohydrates by the rumen ciliate Dasytricha ruminantium isolated from ovine rumen contents by filtration.", "content": "A filtration technique is described whereby metabolically-active suspensions of Dasytricha ruminantium can be isolated from rumen contents with negligible contamination by bacteria or other protozoa. The effects of environmental factors and of the diurnal cycle of the rumen on the uptake and metabolism of soluble carbohydrates by these isolated cells were examined. The principal contribution of the protozoan metabolic end-products to the host ruminant is the supply of lactic, acetic and butyric acids during periods when soluble sugars are in excess.", "contents": "Factors affecting the uptake and metabolism of soluble carbohydrates by the rumen ciliate Dasytricha ruminantium isolated from ovine rumen contents by filtration. A filtration technique is described whereby metabolically-active suspensions of Dasytricha ruminantium can be isolated from rumen contents with negligible contamination by bacteria or other protozoa. The effects of environmental factors and of the diurnal cycle of the rumen on the uptake and metabolism of soluble carbohydrates by these isolated cells were examined. The principal contribution of the protozoan metabolic end-products to the host ruminant is the supply of lactic, acetic and butyric acids during periods when soluble sugars are in excess."}
{"id": "PMID:10344", "title": "Production of phospholipase C (alpha-toxin), haemolysins and lethal toxins by Clostridium perfringens types A to D.", "content": "To obtain high yields of extracellular enzymes and toxins for immunological analysis, type culture collection strains of Clostridium perfringens types A to D and 28 fresh isolates of C. perfringens type A from humans were grown in fermenters under controlled conditions in a pre-reduced proteose peptone medium. The type culture collection strains all showed different characteristics with respect to growth rates and pH optima for growth. Production of phospholipase C (alpha-toxin), haemolysin and lethal activity varied considerably between the different types. Growth and extracellular protein production in fermenters with pH control and static or stirred cultures were compared. Production of all extracellular proteins measured was markedly improved by cultivation in fermenters with pH control. Strain ATCC13124 produced five times more phospholipase C than any of 28 freshly isolated strains of C. perfringens type A, grown under identical conditions. Haemolytic and lethal activities of the ATCC strain were equal or superior to the activities of any of the freshly isolated strains. There were no differences in the bacterial yields and in the production of extracellular toxins between type A strains isolated from clinical cases of gas gangrene and abdominal wounds, and those isolated from faecal samples from healthy persons.", "contents": "Production of phospholipase C (alpha-toxin), haemolysins and lethal toxins by Clostridium perfringens types A to D. To obtain high yields of extracellular enzymes and toxins for immunological analysis, type culture collection strains of Clostridium perfringens types A to D and 28 fresh isolates of C. perfringens type A from humans were grown in fermenters under controlled conditions in a pre-reduced proteose peptone medium. The type culture collection strains all showed different characteristics with respect to growth rates and pH optima for growth. Production of phospholipase C (alpha-toxin), haemolysin and lethal activity varied considerably between the different types. Growth and extracellular protein production in fermenters with pH control and static or stirred cultures were compared. Production of all extracellular proteins measured was markedly improved by cultivation in fermenters with pH control. Strain ATCC13124 produced five times more phospholipase C than any of 28 freshly isolated strains of C. perfringens type A, grown under identical conditions. Haemolytic and lethal activities of the ATCC strain were equal or superior to the activities of any of the freshly isolated strains. There were no differences in the bacterial yields and in the production of extracellular toxins between type A strains isolated from clinical cases of gas gangrene and abdominal wounds, and those isolated from faecal samples from healthy persons."}
{"id": "PMID:10345", "title": "Role of wall phosphomannan in flocculation of Saccharomyces cerevisiae.", "content": "Treatment with 60% hydrofluoric acid (HF) removed most of the phosphorus and small amounts of mannan, glucan and protein from walls of two non-flocculent strains (NCYC366 and NCYC1004) and two flocculent strains (NCYC1005 and NCYC1063) of Saccharomyces cerevisiae. Organisms of all strains showed increased flocculating ability following HF treatment. Flocculation  of untreated organisms of NCYC1005 and NCYC1063, and of HF-treated organisms of all four strains, declined appreciably when they were washed in deionized water, with or without EDTA, and the flocculation was measured in deionized water instead of in 0-05 M-sodium acetate containing Ca2+. Treatment with 1,2-epoxypropane also caused a decrease in the flocculating ability of these organisms. Extracting the lipids from organisms of strains NCYC366 and NCYC1004 had no effect on their flocculating ability, but decreased the flocculating ability of organisms of strains NCYC1005 and NCYC1063. pH-electrophoretic mobility curves of untreated and HF-treated organisms confirmed the loss of wall phosphate by HF treatment, and indicated that HF treatment had little effect on the content of protein carboxyl groups in the outer wall layers. Mannose at 0-22 M completely prevented floc formation by organisms of strain NCYC1063; but, even at 0-33 M, it had very little effect on floc formation by HF-treated organisms of strains NCYC366 and NCYC1063. Organisms of all four strains bound fluorescein-conjugated concanavalin A to the same extent after treatment with HF as before, but this treatment led to a greatly diminished binding of of fluorescein-conjugated antiserum raised against organisms of strain NCYC366. The results indicate that phosphodiester linkages in yeast-wall mannan are not involved in bride formation through Ca2+ during floc formation and that this arises principally through carboxyl groups.", "contents": "Role of wall phosphomannan in flocculation of Saccharomyces cerevisiae. Treatment with 60% hydrofluoric acid (HF) removed most of the phosphorus and small amounts of mannan, glucan and protein from walls of two non-flocculent strains (NCYC366 and NCYC1004) and two flocculent strains (NCYC1005 and NCYC1063) of Saccharomyces cerevisiae. Organisms of all strains showed increased flocculating ability following HF treatment. Flocculation  of untreated organisms of NCYC1005 and NCYC1063, and of HF-treated organisms of all four strains, declined appreciably when they were washed in deionized water, with or without EDTA, and the flocculation was measured in deionized water instead of in 0-05 M-sodium acetate containing Ca2+. Treatment with 1,2-epoxypropane also caused a decrease in the flocculating ability of these organisms. Extracting the lipids from organisms of strains NCYC366 and NCYC1004 had no effect on their flocculating ability, but decreased the flocculating ability of organisms of strains NCYC1005 and NCYC1063. pH-electrophoretic mobility curves of untreated and HF-treated organisms confirmed the loss of wall phosphate by HF treatment, and indicated that HF treatment had little effect on the content of protein carboxyl groups in the outer wall layers. Mannose at 0-22 M completely prevented floc formation by organisms of strain NCYC1063; but, even at 0-33 M, it had very little effect on floc formation by HF-treated organisms of strains NCYC366 and NCYC1063. Organisms of all four strains bound fluorescein-conjugated concanavalin A to the same extent after treatment with HF as before, but this treatment led to a greatly diminished binding of of fluorescein-conjugated antiserum raised against organisms of strain NCYC366. The results indicate that phosphodiester linkages in yeast-wall mannan are not involved in bride formation through Ca2+ during floc formation and that this arises principally through carboxyl groups."}
{"id": "PMID:10346", "title": "Purification and characterization of phosphoglycerate mutase from methanol-grown Hyphomicrobium X and Pseudomonas AM1.", "content": "Phosphoglycerate mutase has been purified from methanol-grown Hyphomicrobium X and Pseudomonas AMI by acid precipitation, heat treatment, ammonium sulphate fractionation, Sephadex G-50 gel filtration and DEAE-cellulose column chromatography. The purification attained using the Hyphomicrobium X extract was 72-fold, and using the Pseudomonas AMI extract, 140-fold. The enzyme purity, as shown by analytical polyacrylamide gel electrophoresis, was 50% from Hyphomicrobium X and 40% from Pseudomonas AMI. The enzyme activity was associated with one band. The purified preparations did not contain detectable amounts of phosphoglycerate kinase, phosphopyruvate hydratase, phosphoglycerate dehydrogenase or glycerate kinase activity. The molecular weight of the enzymic preparation was 32000 +/- 3000. The enzyme from both organisms was stable at low temperatures and, in the presence of 2,3-diphosphoglyceric acid, could withstand exposure to high temperatures. The enzyme from Pseudomonas AMI has a broad pH optimum at 7-0 to 7-6 whilst the enzyme from Hyphomicrobium X has an optimal activity at pH 7-3. The cofactor 2,3-diphosphoglyceric acid was required for maximum enzyme activity and high concentrations of 2-phosphoglyceric acid were inhibitory. The Km values for the Hyphomicrobium X enzyme were: 3-phosphoglyceric acid, 6-0 X 10(-3) M: 2-phosphoglyceric acid, 6-9 X 10(-4) M; 2,3-diphosphoglyceric acid, 8-0 X 10(-6) M; and for the Pseudomonas AMI ENzyme: 3-4 X 10(-3) M, 3-7 X 10(-4) M and 10 X 10(-6) M respectively. The equilibrium constant for the reaction was 11-3 +/- 2-5 in the direction of 2-phosphoglyceric acid to 3-phosphoglyceric acid and 0-09 +/- 0-02 in the reverse direction. The standard free energy for the reaction proceeding from 2-phosphoglyceric acid to 3-phosphoglyceric acid was -5-84 kJ mol(-1) and in the reverse direction +5-81 kJ mol(-1).", "contents": "Purification and characterization of phosphoglycerate mutase from methanol-grown Hyphomicrobium X and Pseudomonas AM1. Phosphoglycerate mutase has been purified from methanol-grown Hyphomicrobium X and Pseudomonas AMI by acid precipitation, heat treatment, ammonium sulphate fractionation, Sephadex G-50 gel filtration and DEAE-cellulose column chromatography. The purification attained using the Hyphomicrobium X extract was 72-fold, and using the Pseudomonas AMI extract, 140-fold. The enzyme purity, as shown by analytical polyacrylamide gel electrophoresis, was 50% from Hyphomicrobium X and 40% from Pseudomonas AMI. The enzyme activity was associated with one band. The purified preparations did not contain detectable amounts of phosphoglycerate kinase, phosphopyruvate hydratase, phosphoglycerate dehydrogenase or glycerate kinase activity. The molecular weight of the enzymic preparation was 32000 +/- 3000. The enzyme from both organisms was stable at low temperatures and, in the presence of 2,3-diphosphoglyceric acid, could withstand exposure to high temperatures. The enzyme from Pseudomonas AMI has a broad pH optimum at 7-0 to 7-6 whilst the enzyme from Hyphomicrobium X has an optimal activity at pH 7-3. The cofactor 2,3-diphosphoglyceric acid was required for maximum enzyme activity and high concentrations of 2-phosphoglyceric acid were inhibitory. The Km values for the Hyphomicrobium X enzyme were: 3-phosphoglyceric acid, 6-0 X 10(-3) M: 2-phosphoglyceric acid, 6-9 X 10(-4) M; 2,3-diphosphoglyceric acid, 8-0 X 10(-6) M; and for the Pseudomonas AMI ENzyme: 3-4 X 10(-3) M, 3-7 X 10(-4) M and 10 X 10(-6) M respectively. The equilibrium constant for the reaction was 11-3 +/- 2-5 in the direction of 2-phosphoglyceric acid to 3-phosphoglyceric acid and 0-09 +/- 0-02 in the reverse direction. The standard free energy for the reaction proceeding from 2-phosphoglyceric acid to 3-phosphoglyceric acid was -5-84 kJ mol(-1) and in the reverse direction +5-81 kJ mol(-1)."}
{"id": "PMID:10348", "title": "The effects of alkalinity and hypertonicity on the morphology and motility of Leptospira interrogans (biflexa) strain B16.", "content": "Effects of alkalinity and hypertonicity on the motile behaviour of Leptospira interrogans (biflexa) B16 were observed, quantified, and compared with effects previously shown by similar factors on the motility of eubacteria. Leptospira interrogans tolerated relatively high concentrations of hydroxide ions. Motility similar to that in controls was observed at pH values up to 9-8; but at pH 10-0 motility declined sharply with time of exposure, and there was structural alteration, visible as a blebbing of the cell envelope. Unlike the behaviour of eubacteria, immobilization of L. interrogans induced by hydroxide ions could not be reversed by lowering the pH. It is suggested that by restricting entry of hydroxide ions, the cell envelope protects its motility apparatus from adverse effects. Leptospira interrogans was completely immobilized in 0-5 M and 1-0 M-sucrose solutions. Unlike the eubacteria, leptospires were incapable of spontaneous reversion to motile forms and resumption of motility was dependent on both concentration and time of exposure to sucrose. Deuterium oxide did not affect movement, suggesting that even though leptospire endoflagella and the exoflagella of eubacteria are analogous, the motile behaviour of L. interrogans is significantly different from that of eubacteria.", "contents": "The effects of alkalinity and hypertonicity on the morphology and motility of Leptospira interrogans (biflexa) strain B16. Effects of alkalinity and hypertonicity on the motile behaviour of Leptospira interrogans (biflexa) B16 were observed, quantified, and compared with effects previously shown by similar factors on the motility of eubacteria. Leptospira interrogans tolerated relatively high concentrations of hydroxide ions. Motility similar to that in controls was observed at pH values up to 9-8; but at pH 10-0 motility declined sharply with time of exposure, and there was structural alteration, visible as a blebbing of the cell envelope. Unlike the behaviour of eubacteria, immobilization of L. interrogans induced by hydroxide ions could not be reversed by lowering the pH. It is suggested that by restricting entry of hydroxide ions, the cell envelope protects its motility apparatus from adverse effects. Leptospira interrogans was completely immobilized in 0-5 M and 1-0 M-sucrose solutions. Unlike the eubacteria, leptospires were incapable of spontaneous reversion to motile forms and resumption of motility was dependent on both concentration and time of exposure to sucrose. Deuterium oxide did not affect movement, suggesting that even though leptospire endoflagella and the exoflagella of eubacteria are analogous, the motile behaviour of L. interrogans is significantly different from that of eubacteria."}
{"id": "PMID:10349", "title": "Autolysis in strains of viridans streptococci.", "content": "Seven strains of viridans streptococci of the species Streptococcus sanguis, S. mutans and S. mitis were investigated for autolysis. The effect of pH, salt concentration and temperature on the autolytic process was studied in Na2HPO4/NaH2PO4 buffer. Whole cells and walls of all strains autolysed most rapidly at pH values above 7. Autolysis of whole cells of S. sanguis and one strain of S. mitis (ATCC15909) was maximal in 0-05 TO 0-2 M buffer, while the two S. mutans strains and S. mitis ATCC15912 showed maximal autolysis in 0-5 and 1-0 M buffers. Cultures harvested in the stationary phase of growth possessed only slightly decreased autolytic activity compared with those from the exponential phase. Whole cells autolysed more rapidly at 37 degrees C Than at 45 degrees C and 10 degrees C. Autolysis of isolated walls of three strains of S. mitis (ATCC903, ATCC15909 and ATCC15912) was maximal at pH 7-0 AND 7-5 and in 1-0 M buffers. Streptococcus mitis ATCC15909 also showed maximal lysis in 0-01 M and 0-5 M buffers. An endopeptidase action of the autolytic system of S. mitis ATCC15912 was indicated by the progressive release of soluble amino groups during autolysis of the walls. No release of reducing groups was observed. Several free amino acids were released during autolysis of these walls, alanine, lysine and glutamic acid being in greatest quanitity.", "contents": "Autolysis in strains of viridans streptococci. Seven strains of viridans streptococci of the species Streptococcus sanguis, S. mutans and S. mitis were investigated for autolysis. The effect of pH, salt concentration and temperature on the autolytic process was studied in Na2HPO4/NaH2PO4 buffer. Whole cells and walls of all strains autolysed most rapidly at pH values above 7. Autolysis of whole cells of S. sanguis and one strain of S. mitis (ATCC15909) was maximal in 0-05 TO 0-2 M buffer, while the two S. mutans strains and S. mitis ATCC15912 showed maximal autolysis in 0-5 and 1-0 M buffers. Cultures harvested in the stationary phase of growth possessed only slightly decreased autolytic activity compared with those from the exponential phase. Whole cells autolysed more rapidly at 37 degrees C Than at 45 degrees C and 10 degrees C. Autolysis of isolated walls of three strains of S. mitis (ATCC903, ATCC15909 and ATCC15912) was maximal at pH 7-0 AND 7-5 and in 1-0 M buffers. Streptococcus mitis ATCC15909 also showed maximal lysis in 0-01 M and 0-5 M buffers. An endopeptidase action of the autolytic system of S. mitis ATCC15912 was indicated by the progressive release of soluble amino groups during autolysis of the walls. No release of reducing groups was observed. Several free amino acids were released during autolysis of these walls, alanine, lysine and glutamic acid being in greatest quanitity."}
{"id": "PMID:10350", "title": "Antipsychotic drugs and dopamine-mediated responses in Aplysia neurons.", "content": "The effect of antipsychotic drugs was tested on responses to micro-electrophoretically applied dopamine, acetylcholine and 5-hydroxytryptamine in identified neurons of the marine gastropod Aplysia californica. Fluphenazine was able to depress the response to DA in concentration of 10 muM, with 100 muM DA-responses of many neurons were blocked completely. Thioridazine (10 and 100 muM) and haloperidol (50 muM) were also effective in depressing DA-responses, while the non-antipsychotic phenothiazines mepazine (10 and 100 muM) and promethazine (100 muM) had only a slight action on DA-receptors. ACh- and 5-HT-responses were slightly affected only by high concentrations after long lasting perfusion. The investigated drugs had no persistent or only an insignificant effect on resting membrane potential and amplitude of action potentials of the neurons. With haloperidol depolarizing afterpotentials leading to double discharges were observed in some neurons. In a few instances spontaneous EPSPs disappeared with the DA-response under the influence of anti-psychotic drugs. The results render a direct neurophysiological evidence for the blockade of DA-receptors by antipsychotic drugs in correspondence to their clinical efficacy and agree with data from clinical observations and obtained in neurochemical, behavioral and indirect neurophysiological experiments.", "contents": "Antipsychotic drugs and dopamine-mediated responses in Aplysia neurons. The effect of antipsychotic drugs was tested on responses to micro-electrophoretically applied dopamine, acetylcholine and 5-hydroxytryptamine in identified neurons of the marine gastropod Aplysia californica. Fluphenazine was able to depress the response to DA in concentration of 10 muM, with 100 muM DA-responses of many neurons were blocked completely. Thioridazine (10 and 100 muM) and haloperidol (50 muM) were also effective in depressing DA-responses, while the non-antipsychotic phenothiazines mepazine (10 and 100 muM) and promethazine (100 muM) had only a slight action on DA-receptors. ACh- and 5-HT-responses were slightly affected only by high concentrations after long lasting perfusion. The investigated drugs had no persistent or only an insignificant effect on resting membrane potential and amplitude of action potentials of the neurons. With haloperidol depolarizing afterpotentials leading to double discharges were observed in some neurons. In a few instances spontaneous EPSPs disappeared with the DA-response under the influence of anti-psychotic drugs. The results render a direct neurophysiological evidence for the blockade of DA-receptors by antipsychotic drugs in correspondence to their clinical efficacy and agree with data from clinical observations and obtained in neurochemical, behavioral and indirect neurophysiological experiments."}
{"id": "PMID:10351", "title": "N-substituted maleimide inactivation of the response to taste cell stimulation.", "content": "N-Ethylmaleimide (NEM) irreversibly inactivates the response of gustatory cells to stimulation by NaCl, sucrose and hydrogen ions. The rate of inactivation can be measured by monitoring the decay of NaCl-stimulated summated electrophysiological activity at the chorda tympani nerve in the presence of NEM. The observed pseudo first-order rate constants are linear with NEM concentration, and the second-order rate constant is 0.38 M-1 sec-1. Other N-substituted maleimides, such as N-methylmaleimide and N-butylmaleimide, which have ether:water partition coefficient and is essentially ineffective as an inactivator of the NaCl response. These results, together with the observation that the inactivation rate is independent of pH between 4.5 and 7.0, indicate the inactivation site is either intracellular or buried within the cell membrane at a locus inaccessible to most extracellular fluids. The rate of inactivation of the sucrose and HCl responses were measured indirectly and found to be comparable to the NaCl-stimulated inactivation rate, indicating the inhibited event is common to the transduction of the response for all of the stimuli examined. Possible sites of inactivation by N-substituted maleimides are considered in the context for and characterizing receptor-specific as well as other classes of taste cell inhibitors.", "contents": "N-substituted maleimide inactivation of the response to taste cell stimulation. N-Ethylmaleimide (NEM) irreversibly inactivates the response of gustatory cells to stimulation by NaCl, sucrose and hydrogen ions. The rate of inactivation can be measured by monitoring the decay of NaCl-stimulated summated electrophysiological activity at the chorda tympani nerve in the presence of NEM. The observed pseudo first-order rate constants are linear with NEM concentration, and the second-order rate constant is 0.38 M-1 sec-1. Other N-substituted maleimides, such as N-methylmaleimide and N-butylmaleimide, which have ether:water partition coefficient and is essentially ineffective as an inactivator of the NaCl response. These results, together with the observation that the inactivation rate is independent of pH between 4.5 and 7.0, indicate the inactivation site is either intracellular or buried within the cell membrane at a locus inaccessible to most extracellular fluids. The rate of inactivation of the sucrose and HCl responses were measured indirectly and found to be comparable to the NaCl-stimulated inactivation rate, indicating the inhibited event is common to the transduction of the response for all of the stimuli examined. Possible sites of inactivation by N-substituted maleimides are considered in the context for and characterizing receptor-specific as well as other classes of taste cell inhibitors."}
{"id": "PMID:10352", "title": "Increased phosphorylated components of erythrocyte membrane spectrin band II with reference to Duchenne muscular dystrophy.", "content": "Increased erythrocyte band II phosphorylation has been demonstrated in patients with Duchenne muscular dystrophy (DMD). Band II has been purified by preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Isoelectric focusing of purified band II from which SDS has been removed reveals heterogeneity. Band II migrates as multiple bands on isoelectric focusing gels and as a single band on SDS-polyacrylamide gels. The increased phosphorylation in DMD does not occur uniformly in all components of band II. Highly phosphorylated components of band II are present in DMD in which only minimal phosphorylation occurs in controls. These results suggest the presence of an abnormal band II substrate in erythrocyte membranes from DMD patients.", "contents": "Increased phosphorylated components of erythrocyte membrane spectrin band II with reference to Duchenne muscular dystrophy. Increased erythrocyte band II phosphorylation has been demonstrated in patients with Duchenne muscular dystrophy (DMD). Band II has been purified by preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Isoelectric focusing of purified band II from which SDS has been removed reveals heterogeneity. Band II migrates as multiple bands on isoelectric focusing gels and as a single band on SDS-polyacrylamide gels. The increased phosphorylation in DMD does not occur uniformly in all components of band II. Highly phosphorylated components of band II are present in DMD in which only minimal phosphorylation occurs in controls. These results suggest the presence of an abnormal band II substrate in erythrocyte membranes from DMD patients."}
{"id": "PMID:10353", "title": "The histochemical profile of the human masseter. An autopsy and biopsy study.", "content": "A histochemical study has been carried out upon samples of muscle obtained from the human masseter. Sixteen specimens obtained either at autopsy or biopsy have shown that the middle and deep portions of the muscle contain fibres which in their size, histochemical staining properties and number correspond to the appearances noted in most human limb skeletal muscles. By contrast, samples taken from the superficial portion of the masseter demonstrated several unusual characteristics: these included a striking inequality of muscle fibre size in that the Type II fibres were much smaller than those of Type I but exceeded the latter in total number. This part of the muscle also contained, in 6 out of 10 samples, substantial numbers of intermediate fibres identified by myofibrillar ATPase staining. This study has confirmed that the superficial part of the human masseter is different morphologically and presumably functionally from the middle and deep parts of the muscle.", "contents": "The histochemical profile of the human masseter. An autopsy and biopsy study. A histochemical study has been carried out upon samples of muscle obtained from the human masseter. Sixteen specimens obtained either at autopsy or biopsy have shown that the middle and deep portions of the muscle contain fibres which in their size, histochemical staining properties and number correspond to the appearances noted in most human limb skeletal muscles. By contrast, samples taken from the superficial portion of the masseter demonstrated several unusual characteristics: these included a striking inequality of muscle fibre size in that the Type II fibres were much smaller than those of Type I but exceeded the latter in total number. This part of the muscle also contained, in 6 out of 10 samples, substantial numbers of intermediate fibres identified by myofibrillar ATPase staining. This study has confirmed that the superficial part of the human masseter is different morphologically and presumably functionally from the middle and deep parts of the muscle."}
{"id": "PMID:10358", "title": "Effects of stock or purified diet on rat liver enzymes involved in the synthesis of dimethyl selenide.", "content": "Rats fed either a stock deit or a purified diet based on casein were tested for their ability to convert 75Se-sodium selenite to volatile selenium (dimethyl selenide) in vivo. This conversion was also studied in liver and kidney in vitro. When injected with a subacute dose of selenite (2 mg Se/kg), rats previously fed stock diet volatilized more than twice as much of the dose compared to rats fed the purified diet, confirming earlier findings. Parallel dietary effects were also observed in vitro using subcellular fractions incubated with 75Se-selenite, glutathione, TPNH, and S-adenosylmethionine. The 9-000 X g supernate prepared from rats fed stock diet synthesized dimethyl selenide at approximately twice the rate of that prepared from rats fed purified diet. A fourfold higher activity was observed with liver microsomal fractions from rats fed the stock diet, whereas cytosol was slightly more active in rats fed the purified diet. Kidney fractions showed analogous changes with diet, although the activity of kidney microsomal fraction was very low. Only minor differences in the levels of glutathione reductase, nonspecific disulfide reducatse, and non-protein thiols were observed in liver and kidney from rats fed the two diets. Considering the effects of diet on the various enzymes known from our previous studies to be involved in dimethyl selenide synthesis, it was concluded that the enhanced ability of rats fed stock diet to synthesize dimethyl selenide results from the induction of a liver microsomal enzyme, apparently a Se-methyltransferase, caused by unknown substances in the stock diet.", "contents": "Effects of stock or purified diet on rat liver enzymes involved in the synthesis of dimethyl selenide. Rats fed either a stock deit or a purified diet based on casein were tested for their ability to convert 75Se-sodium selenite to volatile selenium (dimethyl selenide) in vivo. This conversion was also studied in liver and kidney in vitro. When injected with a subacute dose of selenite (2 mg Se/kg), rats previously fed stock diet volatilized more than twice as much of the dose compared to rats fed the purified diet, confirming earlier findings. Parallel dietary effects were also observed in vitro using subcellular fractions incubated with 75Se-selenite, glutathione, TPNH, and S-adenosylmethionine. The 9-000 X g supernate prepared from rats fed stock diet synthesized dimethyl selenide at approximately twice the rate of that prepared from rats fed purified diet. A fourfold higher activity was observed with liver microsomal fractions from rats fed the stock diet, whereas cytosol was slightly more active in rats fed the purified diet. Kidney fractions showed analogous changes with diet, although the activity of kidney microsomal fraction was very low. Only minor differences in the levels of glutathione reductase, nonspecific disulfide reducatse, and non-protein thiols were observed in liver and kidney from rats fed the two diets. Considering the effects of diet on the various enzymes known from our previous studies to be involved in dimethyl selenide synthesis, it was concluded that the enhanced ability of rats fed stock diet to synthesize dimethyl selenide results from the induction of a liver microsomal enzyme, apparently a Se-methyltransferase, caused by unknown substances in the stock diet."}
{"id": "PMID:10359", "title": "Nitrogen intake and tumorigenesis in rats injected with 1,2-dimethylhydrazine.", "content": "Tumor incidence was studied in 1,2-dimethylhydrazine (DMH) injected male rats assigned at weaning to isoenergetic casein-sucorse deits containing 7.5%, 15%, or 22.5% protein with or without 2.5% urea. Twenty rats fed each diet were given weekly intraperitoneal injections of DMH (15 mg/kg body weight/week) for the first 24 weeks and 20 were given saline. Of 96 DMH-injected rats necropsied after 28 weeks, 88 were necropsied during the 32nd or final week of the experiment. Adenocarcinomas of the small and large intestine were larger and significantly more numberous in rats fed 15% and 22.5% dietary protein. Keratin producing papillomas of the sebaceous glands of the external ear were observed first at 21 weeks in DMH-injected rats fed 22.5% protein. These were subsequently observed in some rats from all DMH-treated groups. As time progressed, the ear tumors increased in size and number in all groups but the greatest incidence was in the group fed 22.5% protein. No tumors were observed in saline-injected rats. Urea feeding did not increase the number of tumors nor cause changes in pH, urease activity or ammonia concentration of contents of the colon or cecum, or blood cholesterol. As dietary protein increased, cecal ammonia concentrations rose while both colon and cecal pH dropped. Portal blood urea and cholesterol reose as dietary protein was increased. DMH-treated rats had significantly higher concentrations of colon and cecal ammonia and lower blood cholesterol. Altough the rats fed 7.5% protein gained significantly less weight during 0 to 6 weeks of feeding, their weight gain was significantly higher during 6 to 26 weeks. No tumors were found in rats necropsied at 16 weeks.", "contents": "Nitrogen intake and tumorigenesis in rats injected with 1,2-dimethylhydrazine. Tumor incidence was studied in 1,2-dimethylhydrazine (DMH) injected male rats assigned at weaning to isoenergetic casein-sucorse deits containing 7.5%, 15%, or 22.5% protein with or without 2.5% urea. Twenty rats fed each diet were given weekly intraperitoneal injections of DMH (15 mg/kg body weight/week) for the first 24 weeks and 20 were given saline. Of 96 DMH-injected rats necropsied after 28 weeks, 88 were necropsied during the 32nd or final week of the experiment. Adenocarcinomas of the small and large intestine were larger and significantly more numberous in rats fed 15% and 22.5% dietary protein. Keratin producing papillomas of the sebaceous glands of the external ear were observed first at 21 weeks in DMH-injected rats fed 22.5% protein. These were subsequently observed in some rats from all DMH-treated groups. As time progressed, the ear tumors increased in size and number in all groups but the greatest incidence was in the group fed 22.5% protein. No tumors were observed in saline-injected rats. Urea feeding did not increase the number of tumors nor cause changes in pH, urease activity or ammonia concentration of contents of the colon or cecum, or blood cholesterol. As dietary protein increased, cecal ammonia concentrations rose while both colon and cecal pH dropped. Portal blood urea and cholesterol reose as dietary protein was increased. DMH-treated rats had significantly higher concentrations of colon and cecal ammonia and lower blood cholesterol. Altough the rats fed 7.5% protein gained significantly less weight during 0 to 6 weeks of feeding, their weight gain was significantly higher during 6 to 26 weeks. No tumors were found in rats necropsied at 16 weeks."}
{"id": "PMID:10360", "title": "Digestion and absorption of bovine milk xanthine oxidase and its role as an aldehyde oxidase.", "content": "The effects of acidic and intestinal proteolytic environments on bovine milk xanthine oxidase (XO) activity were determined in order to evaluate the extent to which this enzyme was absorbed in biologically active form. The inhibition of XO by folic acid and the relative affinities of XO for the oxidation of palmitaldehyde, stearaldehyde, and xanthine were compared. The effects of acid and gastric juice on XO activity were measured by incubating purified enzyme, and non-purified enzyme (milk), in buffers ranging in pH from 2 to 9. Fresh gastric juice was also incubated with milk. Increasing amounts of the enzyme were inactivated as the pH of the incubation mixture was reduced below pH 6.5. Below pH 3.5, the enzyme was completely inactivated. Gastric juice, pH juice incubated with milk. Milk XO activity was reduced 36% when mild was incubated with an equal volume of gastric juice. Homogenized milk had 59% less XO activity compared with raw molk. Fresh raw milk XO, homogenized milk XO, and purified XO were equally susceptible to inactivation by acid or gastric juice. After incubation of milk with gastric juice, or gastric juice followed by pancreatin, XO activity was associated with a macromolecule of 300,000 daltons molecular weight and subunits containg activity were not found. It was estimated that 0.00008% of the XO in the intestine was absorbed. Both folic acid and allopurinol inhibited XO activity in vitro. Allopurinol was 3.5 times more potent an inhibitor than folic acid. A large excess of dietary folic acid did not reduce rat liver or intestinal XO activity in vivo. XO had a much greater affinity for xanthine than for palmitaldehyde or stearaldehyde substrates. It was estimated that of 100 mg of XO in fresh raw milk, 41 mg remained after homogenization, 27 mg entered the intestine and only 20 ng were absorbed as intact enzyme.", "contents": "Digestion and absorption of bovine milk xanthine oxidase and its role as an aldehyde oxidase. The effects of acidic and intestinal proteolytic environments on bovine milk xanthine oxidase (XO) activity were determined in order to evaluate the extent to which this enzyme was absorbed in biologically active form. The inhibition of XO by folic acid and the relative affinities of XO for the oxidation of palmitaldehyde, stearaldehyde, and xanthine were compared. The effects of acid and gastric juice on XO activity were measured by incubating purified enzyme, and non-purified enzyme (milk), in buffers ranging in pH from 2 to 9. Fresh gastric juice was also incubated with milk. Increasing amounts of the enzyme were inactivated as the pH of the incubation mixture was reduced below pH 6.5. Below pH 3.5, the enzyme was completely inactivated. Gastric juice, pH juice incubated with milk. Milk XO activity was reduced 36% when mild was incubated with an equal volume of gastric juice. Homogenized milk had 59% less XO activity compared with raw molk. Fresh raw milk XO, homogenized milk XO, and purified XO were equally susceptible to inactivation by acid or gastric juice. After incubation of milk with gastric juice, or gastric juice followed by pancreatin, XO activity was associated with a macromolecule of 300,000 daltons molecular weight and subunits containg activity were not found. It was estimated that 0.00008% of the XO in the intestine was absorbed. Both folic acid and allopurinol inhibited XO activity in vitro. Allopurinol was 3.5 times more potent an inhibitor than folic acid. A large excess of dietary folic acid did not reduce rat liver or intestinal XO activity in vivo. XO had a much greater affinity for xanthine than for palmitaldehyde or stearaldehyde substrates. It was estimated that of 100 mg of XO in fresh raw milk, 41 mg remained after homogenization, 27 mg entered the intestine and only 20 ng were absorbed as intact enzyme."}
{"id": "PMID:10363", "title": "The formation of a platelet adhesive factor by disruption of the creatine phosphokinase molecule.", "content": "It was discovered that the product of a mix containing the enzyme creatine phosphokinase (CPK) and either glutathione (GSH) or cysteine caused platelets to adhere together in vitro. This platelet adhesive factor (PAF) was formed as CPK enzyme activity declined. An alternative method for the destruction of enzyme activity--heat at 56 degrees C--also resulted in the formation of an in-vitro active PAF which was both less stable and active than its chemically produced counterpart. Assay of the platelet adhesive potency of the CPK-GSH mix, using human platelets, revealed a wide variation in the response of different individuals' platelets to standard quantities of PAF. The nature of this preparation of PAF was investigated by both biochemical and biophysical means, including ion exchange chromatography, electrophoresis, amino acid analysis and analytical ultracentrifuge studies. Evidence is presented that PAF is the product of the disruption of the dimeric structure of the CPK molecule. PAF was found to adhere to paper, under the conditions of electrophoresis imposed, and also to cause sephadex beads to bind together, characteristics which suggested that the platelet adhesion reaction was probably a biophysical process. Red and white cells were not similarly affected. The feasibility of this novel concept for the initiation of platelet adhesion, as a naturally occurring process, was supported by the results of animal experiments in which a statistically depression of platelets in the systemic circulation followed the intravascular administration of PAF. The possible relevance to man of this basic mechanism in relation to exercise and disease processes, including ideopathic and post-traumatic thrombosis, atherogenesis, and dysbaric aseptic necrosis of bone, is discussed.", "contents": "The formation of a platelet adhesive factor by disruption of the creatine phosphokinase molecule. It was discovered that the product of a mix containing the enzyme creatine phosphokinase (CPK) and either glutathione (GSH) or cysteine caused platelets to adhere together in vitro. This platelet adhesive factor (PAF) was formed as CPK enzyme activity declined. An alternative method for the destruction of enzyme activity--heat at 56 degrees C--also resulted in the formation of an in-vitro active PAF which was both less stable and active than its chemically produced counterpart. Assay of the platelet adhesive potency of the CPK-GSH mix, using human platelets, revealed a wide variation in the response of different individuals' platelets to standard quantities of PAF. The nature of this preparation of PAF was investigated by both biochemical and biophysical means, including ion exchange chromatography, electrophoresis, amino acid analysis and analytical ultracentrifuge studies. Evidence is presented that PAF is the product of the disruption of the dimeric structure of the CPK molecule. PAF was found to adhere to paper, under the conditions of electrophoresis imposed, and also to cause sephadex beads to bind together, characteristics which suggested that the platelet adhesion reaction was probably a biophysical process. Red and white cells were not similarly affected. The feasibility of this novel concept for the initiation of platelet adhesion, as a naturally occurring process, was supported by the results of animal experiments in which a statistically depression of platelets in the systemic circulation followed the intravascular administration of PAF. The possible relevance to man of this basic mechanism in relation to exercise and disease processes, including ideopathic and post-traumatic thrombosis, atherogenesis, and dysbaric aseptic necrosis of bone, is discussed."}
{"id": "PMID:10365", "title": "Proteinase activity in Ascaris suum eggs, hatching fluid, and excretions-secretions.", "content": "Hatching fluid and the excretions and secretions (E.S.) of hatched larvae of Ascaris suum revealed proteinase activity when assayed by 2 different procedures employing collagen or casein as substrates. Both assays apparently detected similar levels of proteinase activity in hatching fluid and E.S. of hatched larvae. The Anson (casein substrate) assay worked best in 0.05 M phosphate buffer, pH 8.0. The Azocoll (collagen substrate) assay worked best in 0.05 M borate buffer at pH 8.8. Azocoll assays done at temperatures ranging from 25 to 65 C revealed maximal proteinase activity at 55 C. Analysis of hatching fluid from 18-, 21-, and 28-day-old embryos and of extracts from sonicated 0- to 28-day-old developmental stages showed that proteinase activity increased markedly 18 days after embryonation had begun. Prior to the 18th day of embryonation proteinase levels were relatively low.", "contents": "Proteinase activity in Ascaris suum eggs, hatching fluid, and excretions-secretions. Hatching fluid and the excretions and secretions (E.S.) of hatched larvae of Ascaris suum revealed proteinase activity when assayed by 2 different procedures employing collagen or casein as substrates. Both assays apparently detected similar levels of proteinase activity in hatching fluid and E.S. of hatched larvae. The Anson (casein substrate) assay worked best in 0.05 M phosphate buffer, pH 8.0. The Azocoll (collagen substrate) assay worked best in 0.05 M borate buffer at pH 8.8. Azocoll assays done at temperatures ranging from 25 to 65 C revealed maximal proteinase activity at 55 C. Analysis of hatching fluid from 18-, 21-, and 28-day-old embryos and of extracts from sonicated 0- to 28-day-old developmental stages showed that proteinase activity increased markedly 18 days after embryonation had begun. Prior to the 18th day of embryonation proteinase levels were relatively low."}
{"id": "PMID:10366", "title": "Prostaglandins and leucotaxis.", "content": "Freshly prepared solutions of prostaglandin E1 exhibit chemotactic activity against rabbit polymorphonuclear leucocytes harvested from the peritoneal cavity but are devoid of such activity either against similar cells obtained from the rat or against polymorphonuclear leucocytes obtained from the blood of the rabbit, rat and man. Some implications of these findings with respect to the development of inflammatory responses and the mode of action of non-steroidal acidic anti-inflammatory drugs are discussed.", "contents": "Prostaglandins and leucotaxis. Freshly prepared solutions of prostaglandin E1 exhibit chemotactic activity against rabbit polymorphonuclear leucocytes harvested from the peritoneal cavity but are devoid of such activity either against similar cells obtained from the rat or against polymorphonuclear leucocytes obtained from the blood of the rabbit, rat and man. Some implications of these findings with respect to the development of inflammatory responses and the mode of action of non-steroidal acidic anti-inflammatory drugs are discussed."}
{"id": "PMID:10367", "title": "Pharmacological studies with adenine, adenosine and some phosphorylated derivatives on guinea-pig tracheal muscle.", "content": "Adenine, adenosine and three adenine nucleotides all caused relaxation of the guinea-pig trachea. The relaxation to the nucleotides was often preceded by a contraction. The response to adenosine and the nucleotides, but not adenine, was potentiated by dipyridamole. Imidazole inhibited the response to adenine alone. Propranolol has no effect on the response to any of the compounds. It is concluded that the guinea-pig trachea does not possess and a nucleotide-specific receptor as has been postulated for some other smooth muscle preparations. An alternative hypothesis postulating an adenosine-specific receptor is presented.", "contents": "Pharmacological studies with adenine, adenosine and some phosphorylated derivatives on guinea-pig tracheal muscle. Adenine, adenosine and three adenine nucleotides all caused relaxation of the guinea-pig trachea. The relaxation to the nucleotides was often preceded by a contraction. The response to adenosine and the nucleotides, but not adenine, was potentiated by dipyridamole. Imidazole inhibited the response to adenine alone. Propranolol has no effect on the response to any of the compounds. It is concluded that the guinea-pig trachea does not possess and a nucleotide-specific receptor as has been postulated for some other smooth muscle preparations. An alternative hypothesis postulating an adenosine-specific receptor is presented."}
{"id": "PMID:10368", "title": "Interactions of bradykinin, prostaglandin E1, 5-hydroxytryptamine, histamine and adenosine-5'-triphosphate on the dry leakage response in rat skin.", "content": "Dye leakage in rats produced by intracutaneous injections of irritants was quantitated using an azovan blue technique. Concentration-response lines were obtained for irritants alone and in presence of constant concentrations of other irritants. 5-Hydroxytryptamine (5-HT) (10-7M) potentiated histamine, bradykinin and prostaglandin E1 (PGE1) but inhibited adenosine-5'-triphosphate (ATP). Histamine (10-5M) potentiated bradykinin, PGE1 and ATP. Bradykinin (10-6M) potentiated PGE1 only, but PGE1 (10-6M) potentiated bradykinin, 5-HT and histamine. ATP (10-4M) potentiated 5-HT, histamine and PGE1. Release of ATP during stimulation of sensory nerves might explain enhanced neurogenic oedema observed in skin surrounding an area pretreated with compound 48/80.", "contents": "Interactions of bradykinin, prostaglandin E1, 5-hydroxytryptamine, histamine and adenosine-5'-triphosphate on the dry leakage response in rat skin. Dye leakage in rats produced by intracutaneous injections of irritants was quantitated using an azovan blue technique. Concentration-response lines were obtained for irritants alone and in presence of constant concentrations of other irritants. 5-Hydroxytryptamine (5-HT) (10-7M) potentiated histamine, bradykinin and prostaglandin E1 (PGE1) but inhibited adenosine-5'-triphosphate (ATP). Histamine (10-5M) potentiated bradykinin, PGE1 and ATP. Bradykinin (10-6M) potentiated PGE1 only, but PGE1 (10-6M) potentiated bradykinin, 5-HT and histamine. ATP (10-4M) potentiated 5-HT, histamine and PGE1. Release of ATP during stimulation of sensory nerves might explain enhanced neurogenic oedema observed in skin surrounding an area pretreated with compound 48/80."}
{"id": "PMID:10369", "title": "Polymorphism of disopyramide.", "content": "Two crystal forms of disopyramide have been characterized using X-ray diffraction, differential scanning calorimetry and infrared spectroscopy. The kinetics of the solid state transformation of Form I to Form II has been analysed using the Prout-Tompkins theory. An activation energy of 144 kJ mol-1 is calculated for the system. Dissolution and plasma concentrations show no significant differences in bioavailability between the two polymorphs.", "contents": "Polymorphism of disopyramide. Two crystal forms of disopyramide have been characterized using X-ray diffraction, differential scanning calorimetry and infrared spectroscopy. The kinetics of the solid state transformation of Form I to Form II has been analysed using the Prout-Tompkins theory. An activation energy of 144 kJ mol-1 is calculated for the system. Dissolution and plasma concentrations show no significant differences in bioavailability between the two polymorphs."}
{"id": "PMID:10370", "title": "Aggregation of antiacetylcholine drugs in aqueous solution: monomer concentrations in non-micellar drug systems.", "content": "The self-association of the antiacetylcholine drugs, propantheline bromide, methantheline bromide and methixene hydrochloride in aqueous solution, has been examined by surface tension, light scattering and conductimetric methods. Surface tension graphs were similar to those of conventional surfactants, showing apparent critical micelle concentrations (cmc) at distinct inflection points. Surface tension measurements in the presence of increasing amounts of electrolyte indicated a decrease in the apparent cmc with increase in electrolyte concentration for propantheline bromide. Light scattering curves for propantheline bromide in electrolyte solution showed no significant discontinuity attributable to a cmc. A mode of self association involving aggregate growth by the stepwise addition of monomers was assumed and equilibrium constants for the initial stages of the association were evaluated. An increase in the magnitude of the stepwise association constants with increase in electrolyte concentration was noted. Integration of the light scattering data according to 1n x = oo [(M/Mapp) - 1] dln c (where M and M app are the monomer and apparent aggregate weights respectively and x is the weight fraction of monomers) showed an asymptotic increase in monomer concentration towards a limiting concentration, as the solution concentration, c was increased. Limiting monomer concentrations determined by this method were in reasonable agreement with the apparent cmcs from surface tension studies. It was not possible to detect a cmc for methantheline or propantheline bromide from conductivity measurements.", "contents": "Aggregation of antiacetylcholine drugs in aqueous solution: monomer concentrations in non-micellar drug systems. The self-association of the antiacetylcholine drugs, propantheline bromide, methantheline bromide and methixene hydrochloride in aqueous solution, has been examined by surface tension, light scattering and conductimetric methods. Surface tension graphs were similar to those of conventional surfactants, showing apparent critical micelle concentrations (cmc) at distinct inflection points. Surface tension measurements in the presence of increasing amounts of electrolyte indicated a decrease in the apparent cmc with increase in electrolyte concentration for propantheline bromide. Light scattering curves for propantheline bromide in electrolyte solution showed no significant discontinuity attributable to a cmc. A mode of self association involving aggregate growth by the stepwise addition of monomers was assumed and equilibrium constants for the initial stages of the association were evaluated. An increase in the magnitude of the stepwise association constants with increase in electrolyte concentration was noted. Integration of the light scattering data according to 1n x = oo [(M/Mapp) - 1] dln c (where M and M app are the monomer and apparent aggregate weights respectively and x is the weight fraction of monomers) showed an asymptotic increase in monomer concentration towards a limiting concentration, as the solution concentration, c was increased. Limiting monomer concentrations determined by this method were in reasonable agreement with the apparent cmcs from surface tension studies. It was not possible to detect a cmc for methantheline or propantheline bromide from conductivity measurements."}
{"id": "PMID:10371", "title": "Stability of salicylamide-caffeine complex at different temperatures and its thermodynamic parameters.", "content": "The stability constants for formation of complexes of salicylamide with caffeine have been measured between 15 and 45degrees, by means of the solubility method. There was a linear solubility increase at all temperatures but phase diagrams indicated that at 15 and 25degrees an additional phase was formed which was found to be an insoluble 1 : 1 complex. The enthalpies and entropies of interactions were evaluated. They indicate that the interaction is exothermic and enthalpy controlled.", "contents": "Stability of salicylamide-caffeine complex at different temperatures and its thermodynamic parameters. The stability constants for formation of complexes of salicylamide with caffeine have been measured between 15 and 45degrees, by means of the solubility method. There was a linear solubility increase at all temperatures but phase diagrams indicated that at 15 and 25degrees an additional phase was formed which was found to be an insoluble 1 : 1 complex. The enthalpies and entropies of interactions were evaluated. They indicate that the interaction is exothermic and enthalpy controlled."}
{"id": "PMID:10387", "title": "5-Hydroxytryptamine is a substrate for both species of monoamine oxidase in beef heart mitochondria.", "content": "The activity of beef heart mitochondrial monoamine oxidase towards 5-hydroxytryptamine (5-HT) is inhibited by the selective inhibitors clorgyline, PCO [5-phenyl-3-(N-cyclopropyl)-ethylamine-1,2,4-oxidiazole] and Deprenyl with a biphasic dependence on the inhibitor concentration. The activities towards tyramine, dopamine and tryptamine were also inhibited in a biphasic manner, but the apparent proportions of the two enzyme species active on dopamine and tryptamine depended on the inhibitor used. Phenethylamine oxidation was inhibited in a monophasic manner suggesting that only a single enzyme species was responsible for the oxidation of this substrate. The biphasic response of 5-HT oxidation to inhibition by clorgyline persisted when functionally competent mitochondria were used and was unaffected by the soluble amine oxidase inhibitors semicarbazine and aminoguanidine. These results indicate that the behaviour of the beef heart enzyme towards selective inhibitors is considerably different from that of any preparations previously studied and suggest that the classification of monoamine oxidase activites into A and B types may be only of limited usefulness.", "contents": "5-Hydroxytryptamine is a substrate for both species of monoamine oxidase in beef heart mitochondria. The activity of beef heart mitochondrial monoamine oxidase towards 5-hydroxytryptamine (5-HT) is inhibited by the selective inhibitors clorgyline, PCO [5-phenyl-3-(N-cyclopropyl)-ethylamine-1,2,4-oxidiazole] and Deprenyl with a biphasic dependence on the inhibitor concentration. The activities towards tyramine, dopamine and tryptamine were also inhibited in a biphasic manner, but the apparent proportions of the two enzyme species active on dopamine and tryptamine depended on the inhibitor used. Phenethylamine oxidation was inhibited in a monophasic manner suggesting that only a single enzyme species was responsible for the oxidation of this substrate. The biphasic response of 5-HT oxidation to inhibition by clorgyline persisted when functionally competent mitochondria were used and was unaffected by the soluble amine oxidase inhibitors semicarbazine and aminoguanidine. These results indicate that the behaviour of the beef heart enzyme towards selective inhibitors is considerably different from that of any preparations previously studied and suggest that the classification of monoamine oxidase activites into A and B types may be only of limited usefulness."}
{"id": "PMID:10388", "title": "Bioanalysis of picomole amounts of acetylcholine by ion-pair partition chromatography applied to rat sciatic nerve.", "content": "A method for determination of acetylcholine in small, discrete biological objects by use of ion-pair technique has been developed. Acetylcholine is extracted as an ion pair with 3,5-di-t-butyl-2-hydroxybenzenesulphonate and separated from co-extracted components by ion-pair partition chromatography with picrate as the counter ion and porous cellulose as support. The quantitative evaluation is made from the acetylcholine peak in the chromatogram obtained by ultraviolet detection. Acetylcholine has been analysed in 1 cm large pieces of rat sciatic nerve containing about 60 pmol (10 ng). The overall recovery of the method is 100 +/- 10% at the 120 pmol level of acetylcholine in a sample.", "contents": "Bioanalysis of picomole amounts of acetylcholine by ion-pair partition chromatography applied to rat sciatic nerve. A method for determination of acetylcholine in small, discrete biological objects by use of ion-pair technique has been developed. Acetylcholine is extracted as an ion pair with 3,5-di-t-butyl-2-hydroxybenzenesulphonate and separated from co-extracted components by ion-pair partition chromatography with picrate as the counter ion and porous cellulose as support. The quantitative evaluation is made from the acetylcholine peak in the chromatogram obtained by ultraviolet detection. Acetylcholine has been analysed in 1 cm large pieces of rat sciatic nerve containing about 60 pmol (10 ng). The overall recovery of the method is 100 +/- 10% at the 120 pmol level of acetylcholine in a sample."}
{"id": "PMID:10389", "title": "The effects of administering N-(2-benzoyloxyethyl) norfenfluramine to rats on the hepatic synthesis of glycerolipids.", "content": "N-(2-Benzoyloxyethyl) norfenfluramine (S-780) was administered to rats by stomach tube at a dose of 50 mg kg-1 of body weight. Livers of the rats which were given an acute dose of the drug synthesized more triacylglycerol, phosphatidylcholine and phosphatidylethanolamine from [1,3-3H]glycerol and [14C]palmitate than did those of control rats. The measurements were made by injecting a mixture of the radioactive precursors into the portal veins of anaesthetized rats and freeze clamping a portion of the liver 1 min later. Diffferent results were obtained after treating rats daily with S-780 for 5 days. Liver slices from these rats synthesized less triacylglycerol and relatively more phosphatidylinositol plus phosphatidylserine from [3H]glycerol than did those of control rats. S-780 treatment depressed the hepatic synthesis of phosphatidylcholine and phosphatidylethanolamine as measured in vivo after intrapotal injection of [14C]palmitate and [3H]glycerol. Chronic treatment with S-780 also depressed food intake and lowered liver weight and body weight of rats fed the 41B diet. The results are discussed in relation to the effects of S-780 on the synthesis of glycerolipids.", "contents": "The effects of administering N-(2-benzoyloxyethyl) norfenfluramine to rats on the hepatic synthesis of glycerolipids. N-(2-Benzoyloxyethyl) norfenfluramine (S-780) was administered to rats by stomach tube at a dose of 50 mg kg-1 of body weight. Livers of the rats which were given an acute dose of the drug synthesized more triacylglycerol, phosphatidylcholine and phosphatidylethanolamine from [1,3-3H]glycerol and [14C]palmitate than did those of control rats. The measurements were made by injecting a mixture of the radioactive precursors into the portal veins of anaesthetized rats and freeze clamping a portion of the liver 1 min later. Diffferent results were obtained after treating rats daily with S-780 for 5 days. Liver slices from these rats synthesized less triacylglycerol and relatively more phosphatidylinositol plus phosphatidylserine from [3H]glycerol than did those of control rats. S-780 treatment depressed the hepatic synthesis of phosphatidylcholine and phosphatidylethanolamine as measured in vivo after intrapotal injection of [14C]palmitate and [3H]glycerol. Chronic treatment with S-780 also depressed food intake and lowered liver weight and body weight of rats fed the 41B diet. The results are discussed in relation to the effects of S-780 on the synthesis of glycerolipids."}
{"id": "PMID:10390", "title": "Influence of various substances on prostaglandin biosynthesis by guinea-pig chopped lung.", "content": "Guinea-pig chopped lung tissue was used to investigate the inhibitory effect of various steroidal and non-steroidal anti-inflammatory agents, antipyretics, analgesics, local anaesthetics and psychotropic drugs on mechanically induced release of prostaglandin-like material. Low concentrations of non-steroidal anti-inflammatory agents inhibited synthesis, but other antipyretics and analgesics, and the local anaesthetics had little effect. Thymoleptics, neuroleptics and monoamine oxidase inhibitors except phenelzine exhibited weak activity. It is concluded that the method is a useful pharmacological model to study prostaglandin biosynthesis. The weak effects of the psychotropic drugs suggest that they do not exert their clinical effect by inhibiting PG biosynthesis.", "contents": "Influence of various substances on prostaglandin biosynthesis by guinea-pig chopped lung. Guinea-pig chopped lung tissue was used to investigate the inhibitory effect of various steroidal and non-steroidal anti-inflammatory agents, antipyretics, analgesics, local anaesthetics and psychotropic drugs on mechanically induced release of prostaglandin-like material. Low concentrations of non-steroidal anti-inflammatory agents inhibited synthesis, but other antipyretics and analgesics, and the local anaesthetics had little effect. Thymoleptics, neuroleptics and monoamine oxidase inhibitors except phenelzine exhibited weak activity. It is concluded that the method is a useful pharmacological model to study prostaglandin biosynthesis. The weak effects of the psychotropic drugs suggest that they do not exert their clinical effect by inhibiting PG biosynthesis."}
{"id": "PMID:10391", "title": "Metabolic N-oxidation of atropine, hyoscine and the corresponding nor-alkaloids by guinea-pig liver microsomal preparations.", "content": "Incubation of guinea-pig liver microsomal preparations with atropine or hyoscine resulted in the formation of the corresponding nor-alkaloids and both isomers of atropine N-oxide from atropine and one isomer of hyoscine N-oxide from hyoscine. Separate incubations of guinea-pig liver microsomal preparations with nor-atropine and nor-hyoscine yielded the corresponding hydroxylamines. The N-oxide and hydroxylamine metabolites were identified by comparison of their t.l.c. behavior and m.x. with prepared compounds and also by their reduction to the corresponding tertiary or secondary amines.", "contents": "Metabolic N-oxidation of atropine, hyoscine and the corresponding nor-alkaloids by guinea-pig liver microsomal preparations. Incubation of guinea-pig liver microsomal preparations with atropine or hyoscine resulted in the formation of the corresponding nor-alkaloids and both isomers of atropine N-oxide from atropine and one isomer of hyoscine N-oxide from hyoscine. Separate incubations of guinea-pig liver microsomal preparations with nor-atropine and nor-hyoscine yielded the corresponding hydroxylamines. The N-oxide and hydroxylamine metabolites were identified by comparison of their t.l.c. behavior and m.x. with prepared compounds and also by their reduction to the corresponding tertiary or secondary amines."}
{"id": "PMID:10392", "title": "The microsomal N-oxidation of phentermine.", "content": "The microsomal N-oxidation of phentermine (Ia) to N-hydroxyphentermine (Ib) and to alpha,alpha-dimethyl-alpha-nitroso-beta-phenylethane (Ic was investigated. Maximum activities were obtained with microsomal (9000 g supernatant and microsomes) fractions of rabbit liver in the presence of an NADPH generating system. Incubation of Ia with hepatic washed microsomes from a phenobarbitone pretreated rabbit increased the formation of Ib and decreased that of Ic but the total amount of N-oxidized metabolites (i.e. Ib + Ic) was not affected. The ratio of the metabolically produced Ic to Ib but not the total amount of N-oxygenated metabolites varied greatly depending of the liver microsomal fractions used in the incubation mixtures of Ia; more Ib was produced from Ia using 9000 g supernatant and conversely, more Ic was formed using the washed microsomes of the same liver. The nitroso compound (Ic) was metabolically reduced to Ib and Ib to Ia by the hepatic 9000 g supernatant and soluble fraction; under the same conditions, washed microsomes had only limited reductive properties towards Ic and Ib. N-Hydroxyphentermine (Ib) was not metabolically oxidized to Ic when incubated with washed microsomes from rabbit liver. The use of known carbon-oxidation inhibitors showed that cytochrome P-450 is not involved in the incorporation of oxygen at the nitrogen centre of Ia. The metabolic characteristics and kinetic behavior of the microsomal N-oxidation of Ia supported a recently proposed mechanism explaining the independent formation of Ib and Ic from a common precursor resulting from metabolic N-oxidation of Ia.", "contents": "The microsomal N-oxidation of phentermine. The microsomal N-oxidation of phentermine (Ia) to N-hydroxyphentermine (Ib) and to alpha,alpha-dimethyl-alpha-nitroso-beta-phenylethane (Ic was investigated. Maximum activities were obtained with microsomal (9000 g supernatant and microsomes) fractions of rabbit liver in the presence of an NADPH generating system. Incubation of Ia with hepatic washed microsomes from a phenobarbitone pretreated rabbit increased the formation of Ib and decreased that of Ic but the total amount of N-oxidized metabolites (i.e. Ib + Ic) was not affected. The ratio of the metabolically produced Ic to Ib but not the total amount of N-oxygenated metabolites varied greatly depending of the liver microsomal fractions used in the incubation mixtures of Ia; more Ib was produced from Ia using 9000 g supernatant and conversely, more Ic was formed using the washed microsomes of the same liver. The nitroso compound (Ic) was metabolically reduced to Ib and Ib to Ia by the hepatic 9000 g supernatant and soluble fraction; under the same conditions, washed microsomes had only limited reductive properties towards Ic and Ib. N-Hydroxyphentermine (Ib) was not metabolically oxidized to Ic when incubated with washed microsomes from rabbit liver. The use of known carbon-oxidation inhibitors showed that cytochrome P-450 is not involved in the incorporation of oxygen at the nitrogen centre of Ia. The metabolic characteristics and kinetic behavior of the microsomal N-oxidation of Ia supported a recently proposed mechanism explaining the independent formation of Ib and Ic from a common precursor resulting from metabolic N-oxidation of Ia."}
{"id": "PMID:10393", "title": "A new class of irreversible muscarinic antagonists: beta-haloethylamine furoates.", "content": "The synthesis of a class of ultra-long acting muscarinic antagonists is described. Furthermore, it is noted that the stability of the, in situ, aziridinium ion is sufficiently great so that these agents can be used to study the effect of temperature upon the conformation of the muscarinic cholinoceptor. The inactivation kinetics of these receptors as well as the dissociation constants, Kd, for all probes are presented.", "contents": "A new class of irreversible muscarinic antagonists: beta-haloethylamine furoates. The synthesis of a class of ultra-long acting muscarinic antagonists is described. Furthermore, it is noted that the stability of the, in situ, aziridinium ion is sufficiently great so that these agents can be used to study the effect of temperature upon the conformation of the muscarinic cholinoceptor. The inactivation kinetics of these receptors as well as the dissociation constants, Kd, for all probes are presented."}
{"id": "PMID:10394", "title": "The influence of polyvinylpyrrolidone on the solution and bioavailability of hydrochlorothiazide.", "content": "The dissolution properties of hydrochlorothiazide-PVP 10 000 mechanical mix and coprecipitate systems were qualitatively similar to those previously reported using hydroflumethiazide. Quantitative differences were dependent on the proportion of PVP present, its molecular weight and method of incorporation. Cumulative urinary excretion data from test capsule preparations showed that bioavailability was enhanced by the presence of PVP. However, the degree of enhancement was less than that expected from constant surface area disc rate studies. Dissolution tests on the capsule formulations, using the U.S.P. basket stirrer assembly, did not correlate with in vivo results. Using the Levy beaker method and a stirring speed of 40 rev min-1, good correlation between amount dissolved in 30 min and amount excreted in urine after 24 h was obtained. The dissolution tests revealed that PVP retards the initial dissolution from capsule dosage forms, probably by retarding deaggregation and dispersion of drug particles.", "contents": "The influence of polyvinylpyrrolidone on the solution and bioavailability of hydrochlorothiazide. The dissolution properties of hydrochlorothiazide-PVP 10 000 mechanical mix and coprecipitate systems were qualitatively similar to those previously reported using hydroflumethiazide. Quantitative differences were dependent on the proportion of PVP present, its molecular weight and method of incorporation. Cumulative urinary excretion data from test capsule preparations showed that bioavailability was enhanced by the presence of PVP. However, the degree of enhancement was less than that expected from constant surface area disc rate studies. Dissolution tests on the capsule formulations, using the U.S.P. basket stirrer assembly, did not correlate with in vivo results. Using the Levy beaker method and a stirring speed of 40 rev min-1, good correlation between amount dissolved in 30 min and amount excreted in urine after 24 h was obtained. The dissolution tests revealed that PVP retards the initial dissolution from capsule dosage forms, probably by retarding deaggregation and dispersion of drug particles."}
{"id": "PMID:10395", "title": "Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man.", "content": "Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg-1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a \"simplex\" non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (W1) attributed to individual data points. The plasma half-life of paracetamol varied by up to a seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors.", "contents": "Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man. Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg-1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a \"simplex\" non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (W1) attributed to individual data points. The plasma half-life of paracetamol varied by up to a seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors."}
{"id": "PMID:10408", "title": "Electrochemistry of drug action I: electrooreduction of ferredoxins.", "content": "Ferredoxin serves as an electron carrier in the oxidation-reduction system in anaerobic microorganisms, transferring electrons from a low potential donor to electron-accepting biochemicals. The anaerobicidal activity of some drugs may be due to their interference with the electron transport function of ferredoxin. Two types of ferredoxins (isolated from Clostridium pasteurianum and spinach) were studied, and their electrochemical reduction and biochemical properties were analyzed using a sensitive ac polarographic technique. The reduction potential of both ferredoxins was linearly related to pH. The mechanisms of electron transport in ferredoxin molecules were found to be related to their sulfur-iron bonds. The dissociation of the sulfur-iron bonds resulted in the formation of a free sulfhydryl group and the interruption of the electroactivity of ferredoxin. This sulfur-iron dissociation process was found to be pH dependent. The electroreduction of ferredoxins was an energy-requiring, pH-dependent process.", "contents": "Electrochemistry of drug action I: electrooreduction of ferredoxins. Ferredoxin serves as an electron carrier in the oxidation-reduction system in anaerobic microorganisms, transferring electrons from a low potential donor to electron-accepting biochemicals. The anaerobicidal activity of some drugs may be due to their interference with the electron transport function of ferredoxin. Two types of ferredoxins (isolated from Clostridium pasteurianum and spinach) were studied, and their electrochemical reduction and biochemical properties were analyzed using a sensitive ac polarographic technique. The reduction potential of both ferredoxins was linearly related to pH. The mechanisms of electron transport in ferredoxin molecules were found to be related to their sulfur-iron bonds. The dissociation of the sulfur-iron bonds resulted in the formation of a free sulfhydryl group and the interruption of the electroactivity of ferredoxin. This sulfur-iron dissociation process was found to be pH dependent. The electroreduction of ferredoxins was an energy-requiring, pH-dependent process."}
{"id": "PMID:10409", "title": "Liquid chromatography in pharmaceutical analysis V: determination of an isoniazid-pyridoxine hydrochloride mixture.", "content": "Operating parameters are described for the qualitative and quantitative analysis of an isoniazid-pyridoxine hydrochloride mixture by high-pressure liquid chromatography. Each compound was chromatographed on an octadecyl column, using absolute methanol-water (60:40) (pH 2.5) containing 0.01 M dioctyl sodium sulfosuccinate. The flow rate was 2.0 ml/min (2500 psig), and the peaks were detected at 293 nm. The analysis was accomplished using ion-pair formation for effecting chromatographic separation. The time required for separation of the drug mixture is approximately 12 min with an accuracy of 1.17-0.30%.", "contents": "Liquid chromatography in pharmaceutical analysis V: determination of an isoniazid-pyridoxine hydrochloride mixture. Operating parameters are described for the qualitative and quantitative analysis of an isoniazid-pyridoxine hydrochloride mixture by high-pressure liquid chromatography. Each compound was chromatographed on an octadecyl column, using absolute methanol-water (60:40) (pH 2.5) containing 0.01 M dioctyl sodium sulfosuccinate. The flow rate was 2.0 ml/min (2500 psig), and the peaks were detected at 293 nm. The analysis was accomplished using ion-pair formation for effecting chromatographic separation. The time required for separation of the drug mixture is approximately 12 min with an accuracy of 1.17-0.30%."}
{"id": "PMID:10410", "title": "Simple and rapid determination of a new pharmaceutically active amine hydrochloride.", "content": "The quantitative analysis of a new pharmaceutically active amine hydrochloride is described. Samples are extracted with chloroform. A yellow amine-dye complex is formed by buffering a sample-bromthymol blue solution at pH 8.5 +/- 0.1 and subsequently extracted with chloroform. The complex is treated with 0.01 N NaOH to convert it back to the sodium salt of bromthymol blue, which is then measured at 615 nm in the aqueous layer. The amount of complex extracted is linearly related to the amount of amine present, from 0.020 to 0.20 mg/ml. Under the selected conditions, the compound can be determined in the presence of degradation products and there is no interference from common pharmaceutical excipients. The method is suitable for stability studies.", "contents": "Simple and rapid determination of a new pharmaceutically active amine hydrochloride. The quantitative analysis of a new pharmaceutically active amine hydrochloride is described. Samples are extracted with chloroform. A yellow amine-dye complex is formed by buffering a sample-bromthymol blue solution at pH 8.5 +/- 0.1 and subsequently extracted with chloroform. The complex is treated with 0.01 N NaOH to convert it back to the sodium salt of bromthymol blue, which is then measured at 615 nm in the aqueous layer. The amount of complex extracted is linearly related to the amount of amine present, from 0.020 to 0.20 mg/ml. Under the selected conditions, the compound can be determined in the presence of degradation products and there is no interference from common pharmaceutical excipients. The method is suitable for stability studies."}
{"id": "PMID:10411", "title": "Phenylbutazone ionization kinetics.", "content": "Phenylbutazone has been associated with bioavailability problems and has shown nonclassical behavior in phase-transport studies. This nonclassical behavior has been attributed, in part, to the fact that phenylbutazone, as a carbon acid, undergoes noninstantaneous ionization kinetics. Instantaneous reaction is an assumption made in many diffusion-limited transport models involving a simultaneous ionization reaction. The ionization kinetics of phenylbutazone were determined at an ionic strength of 0.1 and 25 degrees using a stopped-flow spectrophotometer. A log kobs versus pH profile for the approach to the ionization equilibrium was determined, and a mechanism consistent with the profile was postulated. The percent enol versus the diketo form of phenylbutazone acid as well as pKaenol and pKadiketo was kinetically calculated. The protonation reaction was highly catalyzed by general acids while the deprotonation reaction was highly catalyzed by general bases. The general acid, water, was a poor proton donor to the anionic form (the so-called mesomericanion) of phenylbutazone.", "contents": "Phenylbutazone ionization kinetics. Phenylbutazone has been associated with bioavailability problems and has shown nonclassical behavior in phase-transport studies. This nonclassical behavior has been attributed, in part, to the fact that phenylbutazone, as a carbon acid, undergoes noninstantaneous ionization kinetics. Instantaneous reaction is an assumption made in many diffusion-limited transport models involving a simultaneous ionization reaction. The ionization kinetics of phenylbutazone were determined at an ionic strength of 0.1 and 25 degrees using a stopped-flow spectrophotometer. A log kobs versus pH profile for the approach to the ionization equilibrium was determined, and a mechanism consistent with the profile was postulated. The percent enol versus the diketo form of phenylbutazone acid as well as pKaenol and pKadiketo was kinetically calculated. The protonation reaction was highly catalyzed by general acids while the deprotonation reaction was highly catalyzed by general bases. The general acid, water, was a poor proton donor to the anionic form (the so-called mesomericanion) of phenylbutazone."}
{"id": "PMID:10412", "title": "Conversion of cefamandole nafate to cefamandole sodium.", "content": "The rate of hydrolysis of the formyl moiety of cefamandole nafate was determined as a function of pH, temperature, and concentration of added sodium carbonate or tromethamine. The reaction rate was sensitive to hydroxide ion in the pH 5.5-8.0 range with half-life values of hours to minutes. Hydrolysis was rapid upon the addition of sodium carbonate or tromethamine. Chirality in the 7-D-mandelamido side chain was unaffected by hydrolysis.", "contents": "Conversion of cefamandole nafate to cefamandole sodium. The rate of hydrolysis of the formyl moiety of cefamandole nafate was determined as a function of pH, temperature, and concentration of added sodium carbonate or tromethamine. The reaction rate was sensitive to hydroxide ion in the pH 5.5-8.0 range with half-life values of hours to minutes. Hydrolysis was rapid upon the addition of sodium carbonate or tromethamine. Chirality in the 7-D-mandelamido side chain was unaffected by hydrolysis."}
{"id": "PMID:10413", "title": "Structure of aluminum hydroxide gel I: initial precipitate.", "content": "The initial aluminum hydroxide gel precipitate resulting from the reaction of aluminum chloride or aluminum sulfate with ammonium hydroxide is shown by potentiometric titration, chemical analysis, and the ratio of bound hydroxide to aluminum to fit a polymer model described previously. The formation of polynuclear hydroxyaluminum particles is treated as a stepwise process involving a deprotonation-dehydration mechanism, which results in the formation of six-membered rings; these rings may further coalesce by the same mechanism. The aluminum hydroxide gel precipitated from aluminum chloride can be represented by the formula Al(OH)2.55(Cl)0.45 and probably exists as a polymer of 10 fused six-membered rings. The aluminum hydroxide gel precipitated from aluminum sulfate can be represented by the formula Al(OH)2.30(SO4)0.35. This species probably exists as a polymer of three fused six-membered rings.", "contents": "Structure of aluminum hydroxide gel I: initial precipitate. The initial aluminum hydroxide gel precipitate resulting from the reaction of aluminum chloride or aluminum sulfate with ammonium hydroxide is shown by potentiometric titration, chemical analysis, and the ratio of bound hydroxide to aluminum to fit a polymer model described previously. The formation of polynuclear hydroxyaluminum particles is treated as a stepwise process involving a deprotonation-dehydration mechanism, which results in the formation of six-membered rings; these rings may further coalesce by the same mechanism. The aluminum hydroxide gel precipitated from aluminum chloride can be represented by the formula Al(OH)2.55(Cl)0.45 and probably exists as a polymer of 10 fused six-membered rings. The aluminum hydroxide gel precipitated from aluminum sulfate can be represented by the formula Al(OH)2.30(SO4)0.35. This species probably exists as a polymer of three fused six-membered rings."}
{"id": "PMID:10414", "title": "Structure of aluminum hydroxide gel II: aging mechanism.", "content": "The aging of aluminum hydroxide gel prepared by the reaction of aluminum chloride and ammonium hydroxide was studied by measurement of pH, acid-consuming capacity, hydroxide to aluminum ratio, chloride activity, and X-ray line broadening. The results were consistent with a polymer model involving particle growth by a deprotonation-dehydration mechanism. Anions inhibit this reaction by binding to the positively charged edges of the hydroxyaluminum polymers.", "contents": "Structure of aluminum hydroxide gel II: aging mechanism. The aging of aluminum hydroxide gel prepared by the reaction of aluminum chloride and ammonium hydroxide was studied by measurement of pH, acid-consuming capacity, hydroxide to aluminum ratio, chloride activity, and X-ray line broadening. The results were consistent with a polymer model involving particle growth by a deprotonation-dehydration mechanism. Anions inhibit this reaction by binding to the positively charged edges of the hydroxyaluminum polymers."}
{"id": "PMID:10415", "title": "Structure of aluminum hydroxide gel III: mechanism of stabilization by sorbitol.", "content": "The effect of sorbitol on the aging of aluminum hydroxide gel, prepared by the reaction of aluminum chloride solution with strong ammonia solution to a final pH of 7.0, was studied by potentiometric titration, acid-consuming capacity, pH, hydroxide to aluminum ratio, chloride activity, X-ray diffraction, and IR spectroscopy. Gels containing sorbitol lost less than 10% of their acid-consuming capacity during a 6-month aging period compared with a loss of more than 60% for an identical gel without sorbitol. The mechanism by which sorbitol stabilizes the gel appears to be inhibition of the secondary polymerization reaction which takes place upon aging. Another polyhydroxy compound, quercetin, also stabilizes aluminum hydroxide gel.", "contents": "Structure of aluminum hydroxide gel III: mechanism of stabilization by sorbitol. The effect of sorbitol on the aging of aluminum hydroxide gel, prepared by the reaction of aluminum chloride solution with strong ammonia solution to a final pH of 7.0, was studied by potentiometric titration, acid-consuming capacity, pH, hydroxide to aluminum ratio, chloride activity, X-ray diffraction, and IR spectroscopy. Gels containing sorbitol lost less than 10% of their acid-consuming capacity during a 6-month aging period compared with a loss of more than 60% for an identical gel without sorbitol. The mechanism by which sorbitol stabilizes the gel appears to be inhibition of the secondary polymerization reaction which takes place upon aging. Another polyhydroxy compound, quercetin, also stabilizes aluminum hydroxide gel."}
{"id": "PMID:10416", "title": "Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines I: chlordiazepoxide and demoxepam.", "content": "Differential absorbance spectroscopy was successfully used to follow the hydrolysis kinetics of chlordiazepoxide and demoxepam from pH 1 to 11. Loss of the methylamino group from chlordiazepoxide produced demoxepam. Demoxepam degraded by a parallel consecutive reaction to 2-amino-5-chlorobenzophenone and a glycine derivative. Two intermediates were observed by TLC for demoxepam hydrolysis. One was assigned the open-ring structure resulting from amide hydrolysis, which kinetically appears to be the major mechanistic route leading to the benzophenone product. The other intermediate, representing an alternative but minor pathway, presumably results from initial scission of the azomethine linkage. Protonation of the N-oxide slightly alters the importance of these two pathways. Recyclization of the carboxylic acid intermediate was facile at pH values below the pKa of this intermediate. The stability parameters involving buffer catalysis, ionic strength effects, and temperature dependence of rate constants are reported.", "contents": "Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines I: chlordiazepoxide and demoxepam. Differential absorbance spectroscopy was successfully used to follow the hydrolysis kinetics of chlordiazepoxide and demoxepam from pH 1 to 11. Loss of the methylamino group from chlordiazepoxide produced demoxepam. Demoxepam degraded by a parallel consecutive reaction to 2-amino-5-chlorobenzophenone and a glycine derivative. Two intermediates were observed by TLC for demoxepam hydrolysis. One was assigned the open-ring structure resulting from amide hydrolysis, which kinetically appears to be the major mechanistic route leading to the benzophenone product. The other intermediate, representing an alternative but minor pathway, presumably results from initial scission of the azomethine linkage. Protonation of the N-oxide slightly alters the importance of these two pathways. Recyclization of the carboxylic acid intermediate was facile at pH values below the pKa of this intermediate. The stability parameters involving buffer catalysis, ionic strength effects, and temperature dependence of rate constants are reported."}
{"id": "PMID:10417", "title": "Spectrofluorometric determination of hydroflumethiazide in plasma and urine.", "content": "A rapid, accurate, sensitive, and reproducible assay for hydroflumethiazide in plasma and urine was developed after studies of its UV and fluorescence spectral properties and partitioning behavior. The assay is based on initial extraction from acidified plasma or urine into ether, back-extraction into basic solution followed by acidification to about pH 1, and measurement of the fluorescence derived from the unionized molecule. Analysis of variance indicated no significant differences in assays performed on the same day. The mean recovery was 98.8 +/- 7.4% for plasma over a concentration range of 0.2-2.0 mug/ml. The method is convenient for routine clinical use and has sufficient sensitivity to quantify hydroflumethiazide levels after administration of therapeutic doses.", "contents": "Spectrofluorometric determination of hydroflumethiazide in plasma and urine. A rapid, accurate, sensitive, and reproducible assay for hydroflumethiazide in plasma and urine was developed after studies of its UV and fluorescence spectral properties and partitioning behavior. The assay is based on initial extraction from acidified plasma or urine into ether, back-extraction into basic solution followed by acidification to about pH 1, and measurement of the fluorescence derived from the unionized molecule. Analysis of variance indicated no significant differences in assays performed on the same day. The mean recovery was 98.8 +/- 7.4% for plasma over a concentration range of 0.2-2.0 mug/ml. The method is convenient for routine clinical use and has sufficient sensitivity to quantify hydroflumethiazide levels after administration of therapeutic doses."}
{"id": "PMID:10418", "title": "Spectrofluorometric determination of bufuralol in blood and urine.", "content": "The benzofuran analog bufuralol, a beta-adrenergic blocker, was determined in blood and urine by a specific and sensitive spectrofluorometric assay. The compound was extracted into ether from blood or urine adjusted to pH 10. The ether extract was separated by TLC to resolve the parent drug from any basic metabolites present, and the spots were eluted off the silica gel and quantitated fluorometrically in 0.1 N HCl. The overall recovery of the assay was 85 +/- 3.0%; the sensitivity limit was 2-4 ng/ml of blood or urine, using a 2.5-ml specimen/analysis. The method was applied to the determination of blood levels in a dog following a single 10-mg/kg oral dose and in two human subjects administered a single 20-mg oral dose.", "contents": "Spectrofluorometric determination of bufuralol in blood and urine. The benzofuran analog bufuralol, a beta-adrenergic blocker, was determined in blood and urine by a specific and sensitive spectrofluorometric assay. The compound was extracted into ether from blood or urine adjusted to pH 10. The ether extract was separated by TLC to resolve the parent drug from any basic metabolites present, and the spots were eluted off the silica gel and quantitated fluorometrically in 0.1 N HCl. The overall recovery of the assay was 85 +/- 3.0%; the sensitivity limit was 2-4 ng/ml of blood or urine, using a 2.5-ml specimen/analysis. The method was applied to the determination of blood levels in a dog following a single 10-mg/kg oral dose and in two human subjects administered a single 20-mg oral dose."}
{"id": "PMID:10419", "title": "Kinetics of acid neutralization by aluminum hydroxide gel.", "content": "The rate of acid neutralization by an aluminum hydroxide gel prepared by the reaction of aluminum chloride solution and strong ammonia solution was studied. The decrease in acid-consuming capacity during aging as measured by the USP test is due to a decrease in the rate of reaction rather than to a decrease in equilibrium reactivity. The reactivity profile has three phases, which are shown to be related to the structure of the gel. The rate of loss of reactivity is directly related to the extent of washing.", "contents": "Kinetics of acid neutralization by aluminum hydroxide gel. The rate of acid neutralization by an aluminum hydroxide gel prepared by the reaction of aluminum chloride solution and strong ammonia solution was studied. The decrease in acid-consuming capacity during aging as measured by the USP test is due to a decrease in the rate of reaction rather than to a decrease in equilibrium reactivity. The reactivity profile has three phases, which are shown to be related to the structure of the gel. The rate of loss of reactivity is directly related to the extent of washing."}
{"id": "PMID:10420", "title": "Effect of histamine and antihistamines on renal hemodynamics and functions in the isolated perfused canine kidney.", "content": "Histamine was infused intra-arterially (10-40 mug/min) into isolated blood perfused canine kidneys while functional and hemodynamic parameters were monitored. When perfusion pressure (PP) was kept constant during the infusion of histamine, renal blood flow (RBF) increased from 137 +/- 9 to 181 +/- 9 ml/min (P less than .001). A greater increase in RBF occurred to the inner renal cortex than the outer renal cortex as measured by radioactive microspheres. The fractional outer/inner cortical blood flow changed from 79:21 before histamine to 74:26 during its infusion (P less than .001). Histamine did not alter creatinine clearance (Ccr), urine volume (V), sodium excretion (UNaV) or the fractional excretion of sodium (FENa) or water (FEH20) under these conditions. When renal blood flow was held constant during the infusion of histamine, PP decreased from 126/106 +/- 2 to 100/81 +/- 2 mm Hg (P less than .001). This resulted in a reduction of absolute outer cortical (outer/inner) changed from 77:23 before histamine to 72:28 during its infusion (P less than .001). In contrast to the effects of histamine at constant PP, CCr, V, UNaV, FENa, and FEH20 were decreased when histamine infusion reduced the PP. Administration of the H1 receptor antagonist, diphenhydramine, blocked the hemodynamic effects of histamine whereas the administration of an H2 receptor antagonist, metiamide, did not alter the histamine response. Similar vasodilatory responses to histamine were observed in isolated blood perfused dog and cat kidneys. In contrast, vasoconstrictor responses to histamine occurred in isolated dog and cat kidneys perfused with Krebs' solution and in isolated rabbit kidneys whether perfused with blood or Krebs' solution.", "contents": "Effect of histamine and antihistamines on renal hemodynamics and functions in the isolated perfused canine kidney. Histamine was infused intra-arterially (10-40 mug/min) into isolated blood perfused canine kidneys while functional and hemodynamic parameters were monitored. When perfusion pressure (PP) was kept constant during the infusion of histamine, renal blood flow (RBF) increased from 137 +/- 9 to 181 +/- 9 ml/min (P less than .001). A greater increase in RBF occurred to the inner renal cortex than the outer renal cortex as measured by radioactive microspheres. The fractional outer/inner cortical blood flow changed from 79:21 before histamine to 74:26 during its infusion (P less than .001). Histamine did not alter creatinine clearance (Ccr), urine volume (V), sodium excretion (UNaV) or the fractional excretion of sodium (FENa) or water (FEH20) under these conditions. When renal blood flow was held constant during the infusion of histamine, PP decreased from 126/106 +/- 2 to 100/81 +/- 2 mm Hg (P less than .001). This resulted in a reduction of absolute outer cortical (outer/inner) changed from 77:23 before histamine to 72:28 during its infusion (P less than .001). In contrast to the effects of histamine at constant PP, CCr, V, UNaV, FENa, and FEH20 were decreased when histamine infusion reduced the PP. Administration of the H1 receptor antagonist, diphenhydramine, blocked the hemodynamic effects of histamine whereas the administration of an H2 receptor antagonist, metiamide, did not alter the histamine response. Similar vasodilatory responses to histamine were observed in isolated blood perfused dog and cat kidneys. In contrast, vasoconstrictor responses to histamine occurred in isolated dog and cat kidneys perfused with Krebs' solution and in isolated rabbit kidneys whether perfused with blood or Krebs' solution."}
{"id": "PMID:10421", "title": "Phenacetin: renal tubular transport and intrarenal distribution in the dog.", "content": "In a total of 22 studies in the anesthetized dog, the renal clearnace of phenacetin was measured over a range of plasma concentrations and at different urinary pH and rates of urine flow. Phenacetin is reabsorbed by passive diffusion. The urine/plasma ratio is essentially unity under all conditions. As measured by ultraviolet-spectrophotometric and colorometric methods and by high-pressure liquid chromatography, a labile metabolite appears in urine and renal papilla which upon hydrolysis gives rise to falsely high values for phenacetin. Renal cortical and papillary concentrations were determined in six dogs during hydropenia or diuresis. All tissue/plasma concentration ratios for phenacetin were essentially unity. The results indicate that the papillary localization of the earliest lesions of analgesic nephropathy cannot be attributed to high phenacetin concentrations within the papilla. This is in contrast to acetaminophen, the major metabolite of phenacetin.", "contents": "Phenacetin: renal tubular transport and intrarenal distribution in the dog. In a total of 22 studies in the anesthetized dog, the renal clearnace of phenacetin was measured over a range of plasma concentrations and at different urinary pH and rates of urine flow. Phenacetin is reabsorbed by passive diffusion. The urine/plasma ratio is essentially unity under all conditions. As measured by ultraviolet-spectrophotometric and colorometric methods and by high-pressure liquid chromatography, a labile metabolite appears in urine and renal papilla which upon hydrolysis gives rise to falsely high values for phenacetin. Renal cortical and papillary concentrations were determined in six dogs during hydropenia or diuresis. All tissue/plasma concentration ratios for phenacetin were essentially unity. The results indicate that the papillary localization of the earliest lesions of analgesic nephropathy cannot be attributed to high phenacetin concentrations within the papilla. This is in contrast to acetaminophen, the major metabolite of phenacetin."}
{"id": "PMID:10422", "title": "Loperamide binding to opiate receptor sites of brain and myenteric plexus.", "content": "Loperamide, a new antidiarrheal agent, was tested to determine whether its biological activity involves binding to opiate receptor sites. Loperamide and morphine competitively inhibited 3H-naloxone binding to homogenates a guinea-pig brain and myenteric plexus. The Kp values obtain in the presence of Na+ were: morphine, 9.60-10(-9) M (brain), 1.66-10(-7) M (myenteric plexus); loperamide, 7.20-10(-9) M (brain), 1.33-10(-7) M (myenteric plexus); naloxone, 4.78-10(-10) M (brain), 1.27-10(-9) M (myenteric plexus. In the absence of Na+, binding a loperamide and morphine to brain homogenate was enhanced while the binding of naloxone was reduced. Morphine (IC50 = 7.5-10(-8) M) and loperamide (IC50 = 6.9-10(-9) M) inhibited the electrically induced contractions of longitudinal muscle from guinea-pig ileum, and naloxone competitively antagonized these effects. The Kd value calculated for the interaction of naloxone with binding sites associated with the contracting muscle was between 0.98-10(-9) M and 1.85-10(-9) M. In the mouse hot plate test, subcutaneous administration of morphine (minimal effective dose = 6.6 mugmol/kg) and loperamide (minimal effective dose = 78 mugmol/kg) delayed the response to heat stimuli and this effect was completely blocked by prior administration of naloxone. In the anesthetixed dog, intravenous administration of morphine (100 mug/kg) and loperamide (100 mug/kg) enhanced the contractile activity of circular muscle in proximal and distal duodenum, distal ileum and proximal colon but duodenal longitudinal muscle was relaxed; these effects were completely reversed by subsequent administration of naloxone. It is concluded that loperamide binds to opiate receptor sites and possesses opiate agonist activity both in vivo and in vitro.", "contents": "Loperamide binding to opiate receptor sites of brain and myenteric plexus. Loperamide, a new antidiarrheal agent, was tested to determine whether its biological activity involves binding to opiate receptor sites. Loperamide and morphine competitively inhibited 3H-naloxone binding to homogenates a guinea-pig brain and myenteric plexus. The Kp values obtain in the presence of Na+ were: morphine, 9.60-10(-9) M (brain), 1.66-10(-7) M (myenteric plexus); loperamide, 7.20-10(-9) M (brain), 1.33-10(-7) M (myenteric plexus); naloxone, 4.78-10(-10) M (brain), 1.27-10(-9) M (myenteric plexus. In the absence of Na+, binding a loperamide and morphine to brain homogenate was enhanced while the binding of naloxone was reduced. Morphine (IC50 = 7.5-10(-8) M) and loperamide (IC50 = 6.9-10(-9) M) inhibited the electrically induced contractions of longitudinal muscle from guinea-pig ileum, and naloxone competitively antagonized these effects. The Kd value calculated for the interaction of naloxone with binding sites associated with the contracting muscle was between 0.98-10(-9) M and 1.85-10(-9) M. In the mouse hot plate test, subcutaneous administration of morphine (minimal effective dose = 6.6 mugmol/kg) and loperamide (minimal effective dose = 78 mugmol/kg) delayed the response to heat stimuli and this effect was completely blocked by prior administration of naloxone. In the anesthetixed dog, intravenous administration of morphine (100 mug/kg) and loperamide (100 mug/kg) enhanced the contractile activity of circular muscle in proximal and distal duodenum, distal ileum and proximal colon but duodenal longitudinal muscle was relaxed; these effects were completely reversed by subsequent administration of naloxone. It is concluded that loperamide binds to opiate receptor sites and possesses opiate agonist activity both in vivo and in vitro."}
{"id": "PMID:10423", "title": "Cellular mechanisms of renal tubular transport of I-dopa and its derivatives in the rat: microperfusion studies.", "content": "Proximal tubular transport of L-3,4-dihydroxyphenylalanine (L-dopa) and its derivatives were studied in the rat kidney by microperfusion and capillary perfusion techniques in situ. With the use of microperfusion techniques alone, it was found that L-dopa, L-3-methoxy-4-hydroxyphenylalanine, L-tyrosine and L-phenylalanine rapidly disappeared from the perfusate. The rates of reabsorption were calculated to be 2.05 X 10(-12), 2.13 X 10(-12), 6.35 X 10(-12) and 7.14 X 10(-12) mol/cm/sec, respectively. In contrast, L-alpha-methyldopa and dopamine were only slightly reabsorbed. The permeability coefficients were calculated to be 0.35 X 10(-4) and 0.21 x 10(-4) and 0.21 x 10(-4) cm/sec, respectively. The rate of reabsorption of L-dopa was greatly reduced in the presence of L-phenylalanine in the perfusate, but was not affected by D-dopa. With the stop-flow microperfusion technique with simultaneous capillary perfusion, the zero net flux transtubular concentration difference (deltaC) of labeled dopa was measured. When the initial concentration of 2 mM labeled L-dopa was perfused, the luminal concentration fell to a plateau level of 1.5 mM after a contact time of 20 seconds; i.e., deltaC was 0.5 mM. The net flux was much less than the efflux, suggesting the presence of a secretory or passive back flux of L-dopa. The deltaC of L-dopa was not influenced by the decarboxylase inhibitor, MK-486, and monoamine oxidase inhibitor, pheniprazine, but was significantly reduced by NaCN. Thus the reabsorption of L-dopa in the proximal convoluted tubule is an active process with great structural specificity.", "contents": "Cellular mechanisms of renal tubular transport of I-dopa and its derivatives in the rat: microperfusion studies. Proximal tubular transport of L-3,4-dihydroxyphenylalanine (L-dopa) and its derivatives were studied in the rat kidney by microperfusion and capillary perfusion techniques in situ. With the use of microperfusion techniques alone, it was found that L-dopa, L-3-methoxy-4-hydroxyphenylalanine, L-tyrosine and L-phenylalanine rapidly disappeared from the perfusate. The rates of reabsorption were calculated to be 2.05 X 10(-12), 2.13 X 10(-12), 6.35 X 10(-12) and 7.14 X 10(-12) mol/cm/sec, respectively. In contrast, L-alpha-methyldopa and dopamine were only slightly reabsorbed. The permeability coefficients were calculated to be 0.35 X 10(-4) and 0.21 x 10(-4) and 0.21 x 10(-4) cm/sec, respectively. The rate of reabsorption of L-dopa was greatly reduced in the presence of L-phenylalanine in the perfusate, but was not affected by D-dopa. With the stop-flow microperfusion technique with simultaneous capillary perfusion, the zero net flux transtubular concentration difference (deltaC) of labeled dopa was measured. When the initial concentration of 2 mM labeled L-dopa was perfused, the luminal concentration fell to a plateau level of 1.5 mM after a contact time of 20 seconds; i.e., deltaC was 0.5 mM. The net flux was much less than the efflux, suggesting the presence of a secretory or passive back flux of L-dopa. The deltaC of L-dopa was not influenced by the decarboxylase inhibitor, MK-486, and monoamine oxidase inhibitor, pheniprazine, but was significantly reduced by NaCN. Thus the reabsorption of L-dopa in the proximal convoluted tubule is an active process with great structural specificity."}
{"id": "PMID:10424", "title": "Biosynthesis and metabolism of endogenous tyramine and its normal presence in sympathetic nerves.", "content": "By use of a sensitive and specific enzymatic isotopic method for the determination of tyramine, the small quantities of this amine which are present endogenously in rat tissues, including brain, heart, kidney and salivary gland, have been quantitated. The levels of tyramine in brain were increased to a similar extent by injecting animals with a monoamine oxidase inhibitor, pargyline, and a dopamine beta-hydroxylase inhibitor, FLA-63; in contrast, pretreatment of animals with alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, did not lead to an increase in tyramine levels in brain. Pretreatment of rats with 6-hydroxydopamine resulted in a marked diminution in the tyramine content of rat atria and salivary gland. Denervation of the salivary gland decreased the endogenous level of tyramine approximately 50% in denervated glands compared to undenervated glands. These results suggest that tyramine exists at least partly in sympathetic nerves in many tissues.", "contents": "Biosynthesis and metabolism of endogenous tyramine and its normal presence in sympathetic nerves. By use of a sensitive and specific enzymatic isotopic method for the determination of tyramine, the small quantities of this amine which are present endogenously in rat tissues, including brain, heart, kidney and salivary gland, have been quantitated. The levels of tyramine in brain were increased to a similar extent by injecting animals with a monoamine oxidase inhibitor, pargyline, and a dopamine beta-hydroxylase inhibitor, FLA-63; in contrast, pretreatment of animals with alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, did not lead to an increase in tyramine levels in brain. Pretreatment of rats with 6-hydroxydopamine resulted in a marked diminution in the tyramine content of rat atria and salivary gland. Denervation of the salivary gland decreased the endogenous level of tyramine approximately 50% in denervated glands compared to undenervated glands. These results suggest that tyramine exists at least partly in sympathetic nerves in many tissues."}
{"id": "PMID:10425", "title": "The beta adrenergic receptors of chromatophores of the frog, Rana pipiens.", "content": "The isolated skin of Rana pipiens was found to be a suitable model for the quantitative study of chromatophore beta adrenergic receptors uninfluenced by prejunctional phenomena. Cumulative concentration-response curves for adrenergic agonists were obtained in preparations in which effective alpha adrenergic blockade had been produced with phenoxybenzamine. The beta adrenergic agonists darkened the preparation, as did melanocyte-stimulating hormone, but the maximum effects differed. The maximum of the l-isoproterenol cumulative concentration-response curve was  approximately 50% less than that of melanocyte-stimulating hormone, while the maxima for l-epinephrine and l-norepinephrine were significantly less than that for isoproterenol. Microscopic examination revealed a qualitative difference: while maximal darkening produced by melanocyte-stimulating hormone was associated with maximal changes in both interspot melanophores and iridophores, maximal adrenergic-induced darkening was associated with maximal iridophore granule concentration only. No qualitative differences could be observed in the darkening caused by the three adrenergic agonists. The beta adrenergic potencies of l-norepinephrine and l-isoproterenol relative to l-epinephrine were determined by four-point bioassay. Isoproterenol was found to be 138 times as potent as epinephrine, while norepinephrine was 4 times as potent. Similarly, antagonism of isoproterenol-induced darkening of phenoxybenzamine-pretreated skin samples by the beta adrenergic blocking agents dl-propranolol, dl-sotalol, dl-practolol, l-butoxamine and d-butoxamine was studied, and their KB and pA2 values, respectively, were found to be: dl-propranolol (1.44 X 10(-8)M, 7.81); dl-sotalol (7.25 X 10(-8)M, 7.23); l-butoxamine (6.92 X 10(-6)M, 5.10); dl-practolol (1.91 X 10(-5)M, 4.96); d-butoxamine (no activity). Comparison of the potency ratios and pA2 values cited above with similar parameters obtained by other investigators in several mammalian tissues suggests that there is wide variation among beta adrenergic receptors.", "contents": "The beta adrenergic receptors of chromatophores of the frog, Rana pipiens. The isolated skin of Rana pipiens was found to be a suitable model for the quantitative study of chromatophore beta adrenergic receptors uninfluenced by prejunctional phenomena. Cumulative concentration-response curves for adrenergic agonists were obtained in preparations in which effective alpha adrenergic blockade had been produced with phenoxybenzamine. The beta adrenergic agonists darkened the preparation, as did melanocyte-stimulating hormone, but the maximum effects differed. The maximum of the l-isoproterenol cumulative concentration-response curve was  approximately 50% less than that of melanocyte-stimulating hormone, while the maxima for l-epinephrine and l-norepinephrine were significantly less than that for isoproterenol. Microscopic examination revealed a qualitative difference: while maximal darkening produced by melanocyte-stimulating hormone was associated with maximal changes in both interspot melanophores and iridophores, maximal adrenergic-induced darkening was associated with maximal iridophore granule concentration only. No qualitative differences could be observed in the darkening caused by the three adrenergic agonists. The beta adrenergic potencies of l-norepinephrine and l-isoproterenol relative to l-epinephrine were determined by four-point bioassay. Isoproterenol was found to be 138 times as potent as epinephrine, while norepinephrine was 4 times as potent. Similarly, antagonism of isoproterenol-induced darkening of phenoxybenzamine-pretreated skin samples by the beta adrenergic blocking agents dl-propranolol, dl-sotalol, dl-practolol, l-butoxamine and d-butoxamine was studied, and their KB and pA2 values, respectively, were found to be: dl-propranolol (1.44 X 10(-8)M, 7.81); dl-sotalol (7.25 X 10(-8)M, 7.23); l-butoxamine (6.92 X 10(-6)M, 5.10); dl-practolol (1.91 X 10(-5)M, 4.96); d-butoxamine (no activity). Comparison of the potency ratios and pA2 values cited above with similar parameters obtained by other investigators in several mammalian tissues suggests that there is wide variation among beta adrenergic receptors."}
{"id": "PMID:10426", "title": "A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action.", "content": "Anthopleurin-A (AP-A), a polypeptide with MW ca. 5500 (53 amino acids), isolated from the sea anemone, Anthopleura xanthogrammica (Brandt), elicited a potent positive inotropic effect but without an accompanying chronotropic effect on the isolated cardiac muscles of rat, rabbit, guinea pig and cat. Similarly in dogs and cats in situ, i.p. injections of AP-A increased the contractile force without effect on heart rate or blood pressure. The cardiotonic potency for AP-A was equivalent to that of isoproterenol but much greater than that for ouabain or glucagon on the isolated cardiac muscle. AP-A increased the contractile force (cardiac output) and decreased atrial pressure in dog heart during pentobarbital-induced failure. This inotropic effect was not inhibited by propranolol pretreatment. The Ca++ requirement to restore the contractile force was less in AP-A-treated than in ouabain or isoproterenol-treated tissues. After AP-A treatment, the cardiac contractility was more resistant to hypoxia and to low or high temperature stress than ouabain-treated or control preparations. AP-A at 5 10(-9) M increased the duration of the action potential, its mean rate of rise and conduction in the guinea-pig atria and ventricles. At the maximum effective concentration, AP-A did not inhibit Na+, K+-activated adenosine triphosphatase, phosphodiesterase (high Km and low Km) and cyclic 3',5'-adenosine monophosphate content of guinea-pig heart. AP-A (5 X 10(-8) to 5 X 10(-7) M) neither contracted nor relaxed the isolated vascular smooth muscle. The results suggest that AP-A may be useful in the clinical management of cardiac failure and as an experimental tool to study the pharmacology and physiology of cardiac muscle.", "contents": "A polypeptide (AP-A) from sea anemone (Anthopleura xanthogrammica) with potent positive inotropic action. Anthopleurin-A (AP-A), a polypeptide with MW ca. 5500 (53 amino acids), isolated from the sea anemone, Anthopleura xanthogrammica (Brandt), elicited a potent positive inotropic effect but without an accompanying chronotropic effect on the isolated cardiac muscles of rat, rabbit, guinea pig and cat. Similarly in dogs and cats in situ, i.p. injections of AP-A increased the contractile force without effect on heart rate or blood pressure. The cardiotonic potency for AP-A was equivalent to that of isoproterenol but much greater than that for ouabain or glucagon on the isolated cardiac muscle. AP-A increased the contractile force (cardiac output) and decreased atrial pressure in dog heart during pentobarbital-induced failure. This inotropic effect was not inhibited by propranolol pretreatment. The Ca++ requirement to restore the contractile force was less in AP-A-treated than in ouabain or isoproterenol-treated tissues. After AP-A treatment, the cardiac contractility was more resistant to hypoxia and to low or high temperature stress than ouabain-treated or control preparations. AP-A at 5 10(-9) M increased the duration of the action potential, its mean rate of rise and conduction in the guinea-pig atria and ventricles. At the maximum effective concentration, AP-A did not inhibit Na+, K+-activated adenosine triphosphatase, phosphodiesterase (high Km and low Km) and cyclic 3',5'-adenosine monophosphate content of guinea-pig heart. AP-A (5 X 10(-8) to 5 X 10(-7) M) neither contracted nor relaxed the isolated vascular smooth muscle. The results suggest that AP-A may be useful in the clinical management of cardiac failure and as an experimental tool to study the pharmacology and physiology of cardiac muscle."}
{"id": "PMID:10427", "title": "Isoproterenol antagonism of cardioselective beta adrenergic receptor blocking agents: a comparative study of human and guinea-pig cardiac and bronchial beta adrenergic receptors.", "content": "pA2 values against isoproterenol were determined for a number of cardioselective and noncardioselective beta adrenergic receptor blocking agents using human and guinea-pig isolated atrial and bronchial or tracheal preparations to study possible species differences. No significant differences in pA2 values for propranolol, pindolol, Ro 3-4787, acebutolol, atenolol, practolol, metoprolol, H 87/07 and tolamolol on bronchial or tracheal beta adrenergic receptors of both species were found. With respect to atrial beta adrenergic receptors, significantly lower pA2 values for human preparations, as compared to guinea-pig preparations, were found for tolamolol and CI 775. These are the only two agents in the series that derive their cardioselectivities from specific nitrogen substitutents. The different potencies of only these two compounds in antagonizing isoproterenol on atrial beta adrenergic receptors of both species suggest a difference in an accessory receptor area close to the site that interacts with the nitrogen atom of beta adrenergic agents.", "contents": "Isoproterenol antagonism of cardioselective beta adrenergic receptor blocking agents: a comparative study of human and guinea-pig cardiac and bronchial beta adrenergic receptors. pA2 values against isoproterenol were determined for a number of cardioselective and noncardioselective beta adrenergic receptor blocking agents using human and guinea-pig isolated atrial and bronchial or tracheal preparations to study possible species differences. No significant differences in pA2 values for propranolol, pindolol, Ro 3-4787, acebutolol, atenolol, practolol, metoprolol, H 87/07 and tolamolol on bronchial or tracheal beta adrenergic receptors of both species were found. With respect to atrial beta adrenergic receptors, significantly lower pA2 values for human preparations, as compared to guinea-pig preparations, were found for tolamolol and CI 775. These are the only two agents in the series that derive their cardioselectivities from specific nitrogen substitutents. The different potencies of only these two compounds in antagonizing isoproterenol on atrial beta adrenergic receptors of both species suggest a difference in an accessory receptor area close to the site that interacts with the nitrogen atom of beta adrenergic agents."}
{"id": "PMID:10428", "title": "Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse.", "content": "Interactions between the benzodiazepine derivatives, diazepam and oxazepam, and the narcotic analgesics, morphine and methadone, were evaluated on locomotor activity and in the tail-flick and hot-plate tests for analgesia in the mouse. The dose-related stimulation of locomotor activity by morphine was reduced by diazepam and oxazepam at doses which alone had no effect on locomotor activity. However, only oxazepam reduced the dose-related stimulation of locomotor activity by methadone. The observed decreases produced by diazepam and oxazepam were comparable in magnitude to those produced by naloxone. Stimulation of locomotor activity by d-amphetamine was not affected by either diazepam or oxazepam. Dose-response curves for locomotor activity were also determined with morphine and methadone administered intraventricularly. As before, diazepam and naloxone given i.p. decreased the stimulation of locomotor activity produced by morphine, but only naloxone affected methadone-stimulated locomotor activity. Neither diazepam, oxazepam nor naloxone reduced the brain or plasma levels of 3H-morphine or 3H-methadone. In contrast to the results on locomotor activity, neither of these benzodiazepines significantly modified the dose-response curves of morphine or methadone in either test for analgesia. The mechanisms involved in the observed interactions on locomotor activity may be related to the influences of benzodiazepines and narcotic analgesics on motor efferent pathways summating in such a manner as to interfere with the ability of the mice to locomote. The present results demonstrate that prominent interactions occur between members of the  benzodiazepine and narcotic analgesic classes; these interactions are dependent upon both the specific combination of drugs administered and upon the test procedure.", "contents": "Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. Interactions between the benzodiazepine derivatives, diazepam and oxazepam, and the narcotic analgesics, morphine and methadone, were evaluated on locomotor activity and in the tail-flick and hot-plate tests for analgesia in the mouse. The dose-related stimulation of locomotor activity by morphine was reduced by diazepam and oxazepam at doses which alone had no effect on locomotor activity. However, only oxazepam reduced the dose-related stimulation of locomotor activity by methadone. The observed decreases produced by diazepam and oxazepam were comparable in magnitude to those produced by naloxone. Stimulation of locomotor activity by d-amphetamine was not affected by either diazepam or oxazepam. Dose-response curves for locomotor activity were also determined with morphine and methadone administered intraventricularly. As before, diazepam and naloxone given i.p. decreased the stimulation of locomotor activity produced by morphine, but only naloxone affected methadone-stimulated locomotor activity. Neither diazepam, oxazepam nor naloxone reduced the brain or plasma levels of 3H-morphine or 3H-methadone. In contrast to the results on locomotor activity, neither of these benzodiazepines significantly modified the dose-response curves of morphine or methadone in either test for analgesia. The mechanisms involved in the observed interactions on locomotor activity may be related to the influences of benzodiazepines and narcotic analgesics on motor efferent pathways summating in such a manner as to interfere with the ability of the mice to locomote. The present results demonstrate that prominent interactions occur between members of the  benzodiazepine and narcotic analgesic classes; these interactions are dependent upon both the specific combination of drugs administered and upon the test procedure."}
{"id": "PMID:10429", "title": "Precipitation of abstinence-like syndrome in morphine-dependent mice by pargyline.", "content": "In mice rendered morphine-dependent by pellet implantation for 3 days, the administration of pargyline 6 hours after pellet removal intensified narcotic abstinence behavior, particularly the narcotic withdrawal jumping response. Pargyline, 75 mg/kg i.p., caused a 6- to 9-fold increase in the incidence of jumping in mice withdrawing from morphine 6 hours after removal of the pellet, whereas this effect was not observed: 1) 1 hour after the injection of pargyline or 2) in animals still implanted with the morphine pellet. The median effective dose (ED50) of pargyline required to elicit withdrawal jumping in mice implanted with morphine decreased with increasing physical dependence. The ED50 for 72 hours was about one-sixth that after 24 hours of implantation. Additionally, pargyline potentiated naloxone-precipitated withdrawal jumping as evidenced by a reduction of the naloxone ED50 by approximately one-half. Administration of other monoamine oxidase inhibitors such as pheniprazine, iproiazid or tranylcypromine failed to alter the indicence of jumping in dependent mice undergoind abrupt morphine with drawal. Further, dopamine receptor stimulation by amphetamine, pheniprazine or amantadine antagonized the pargyline-induced jumping response. These data suggest that the increased incidence of withdrawal jumping observed after pargyline in morphine-dependent mice is not related to monoamine oxidase inhibition but rather to a possible pargyline-induced decrease in dopaminergic activity.", "contents": "Precipitation of abstinence-like syndrome in morphine-dependent mice by pargyline. In mice rendered morphine-dependent by pellet implantation for 3 days, the administration of pargyline 6 hours after pellet removal intensified narcotic abstinence behavior, particularly the narcotic withdrawal jumping response. Pargyline, 75 mg/kg i.p., caused a 6- to 9-fold increase in the incidence of jumping in mice withdrawing from morphine 6 hours after removal of the pellet, whereas this effect was not observed: 1) 1 hour after the injection of pargyline or 2) in animals still implanted with the morphine pellet. The median effective dose (ED50) of pargyline required to elicit withdrawal jumping in mice implanted with morphine decreased with increasing physical dependence. The ED50 for 72 hours was about one-sixth that after 24 hours of implantation. Additionally, pargyline potentiated naloxone-precipitated withdrawal jumping as evidenced by a reduction of the naloxone ED50 by approximately one-half. Administration of other monoamine oxidase inhibitors such as pheniprazine, iproiazid or tranylcypromine failed to alter the indicence of jumping in dependent mice undergoind abrupt morphine with drawal. Further, dopamine receptor stimulation by amphetamine, pheniprazine or amantadine antagonized the pargyline-induced jumping response. These data suggest that the increased incidence of withdrawal jumping observed after pargyline in morphine-dependent mice is not related to monoamine oxidase inhibition but rather to a possible pargyline-induced decrease in dopaminergic activity."}
{"id": "PMID:10430", "title": "Effect of sodium para-aminosalicylate on oxygen affinity in normal, sickle and fetal human blood.", "content": "Sodium para-aminosalicylate (sodium salt of 2-hydroxy-4-aminobenzoic acid, Na-PAS) lowers the oxygen affinity of normal adult human placental, heterozygous and homozygous sickle cell anemic whole blood at 37 degrees C. The reduction of oxygen affinity is related to the type of hemoglobin in the blood. The mean P50 +/- S.E. at pH 7.40 for normal, placental, heterozygoud and homozygous sickle cell anemic blood in 26.2 +/- 0.1, 20.8 +/- 0.3, 26.8 +/- 0.3 and 31.0 +/- 0.5 mm Hg; in the presence of 5.7 mmol of Na-PAS per liter of blood the P50 values are increased to 28.0 +/- 0.3, 22.9 +/- 0.8, 30.5 +/- 0.6 and 33.9 +/- 0.3 mm Hg, respectively. The Bohr effect in normal and placental blood at this Na-PAS concentration is essentially unchanged: in heterozygous and homozygous sickle cell anemic blood, the Bohr factor (deta log P50/deta pH) is reduced from -0.48 +/- 0.02 to -0.41 +/- 0.01 and from -0.53 +/- 0.03 to -0.48 +/- 0.01. The Hill constants (n) of normal and placental blood are not affected by Na-PAS. In homozygous and heterozygous sickle blood, high concentrations of Na-PAS (22.9 mmol/l) decrease the Hill constant from 2.55 to 2.35 and from 2.56 to 2.28, respectively. Na-PAS is more firmly bound to red blood cells than to plasma. The binding of Na-PAS is probably primarily ionic in nature since the drug can be almost completely removed from blood components by dialysis. The changes in oxygen affinity caused by Na-PAS are consistent with conformational changes (R leads to T) which enhance the presence of deoxyhemoglobin.", "contents": "Effect of sodium para-aminosalicylate on oxygen affinity in normal, sickle and fetal human blood. Sodium para-aminosalicylate (sodium salt of 2-hydroxy-4-aminobenzoic acid, Na-PAS) lowers the oxygen affinity of normal adult human placental, heterozygous and homozygous sickle cell anemic whole blood at 37 degrees C. The reduction of oxygen affinity is related to the type of hemoglobin in the blood. The mean P50 +/- S.E. at pH 7.40 for normal, placental, heterozygoud and homozygous sickle cell anemic blood in 26.2 +/- 0.1, 20.8 +/- 0.3, 26.8 +/- 0.3 and 31.0 +/- 0.5 mm Hg; in the presence of 5.7 mmol of Na-PAS per liter of blood the P50 values are increased to 28.0 +/- 0.3, 22.9 +/- 0.8, 30.5 +/- 0.6 and 33.9 +/- 0.3 mm Hg, respectively. The Bohr effect in normal and placental blood at this Na-PAS concentration is essentially unchanged: in heterozygous and homozygous sickle cell anemic blood, the Bohr factor (deta log P50/deta pH) is reduced from -0.48 +/- 0.02 to -0.41 +/- 0.01 and from -0.53 +/- 0.03 to -0.48 +/- 0.01. The Hill constants (n) of normal and placental blood are not affected by Na-PAS. In homozygous and heterozygous sickle blood, high concentrations of Na-PAS (22.9 mmol/l) decrease the Hill constant from 2.55 to 2.35 and from 2.56 to 2.28, respectively. Na-PAS is more firmly bound to red blood cells than to plasma. The binding of Na-PAS is probably primarily ionic in nature since the drug can be almost completely removed from blood components by dialysis. The changes in oxygen affinity caused by Na-PAS are consistent with conformational changes (R leads to T) which enhance the presence of deoxyhemoglobin."}
{"id": "PMID:10432", "title": "Drug blockade of open end-plate channels.", "content": "1. The actions of amylobarbitone, thiopentone, methohexitone and methyprylone at voltage-clamped frog end-plates were studied. 2. In the presence of barbiturates the conductance change evoked by an iontophoretic carbachol application was reduced by a prepulse of carbachol. The extra inhibition evoked by a prepulse disappeared exponentially with a time constant of 150-200 ms. 3. Barbiturates produce an increased rate of decay of nerve evoked endplate currents. Tne concentration and voltage dependence of the barbtiruate e.p.c. decay rates tally with the hypothesis that the increased rate of decay is due to block of active receptor-channel complexes by barbiturates with a rate constant of  10(6) M-1S-1. 4. Conductance changes produced by bath applied agonists were depressed by thiopentone, the effect becoming greater the higher the agonist concentration. This effect, and also the observation that the concentration of thiopentone required to depress the bath agonist response is much greater than the apparent dissociation constant for binding to active receptor-channel complexes calculated from kinetic measurements, suggest that the selectivity for binding to open receptor-channel complexes is very high. 5. Methyprylone, which is structurally similar to the barbiturates, is only a weak antagonist and shows no interpulse interaction. It was predicted that methyprylone should produce fast and slow components in the e.p.c. decay, and this prediction was verified. 6. In the presence of barbiturates large iontophoretic carbachol applications produce conductance changes which show fast and slow components. Under these conditions the effects of carbachol prepulses become complex. However the effects are qualitatively consistent with the notion that different components of the response are contributed by channels located at various distances from the iontophoretic pipette tip. 7. All the data agree with a model in which the channel has three stages: closed, open and blocked. Only open channels can block, and blocked channels can only open.", "contents": "Drug blockade of open end-plate channels. 1. The actions of amylobarbitone, thiopentone, methohexitone and methyprylone at voltage-clamped frog end-plates were studied. 2. In the presence of barbiturates the conductance change evoked by an iontophoretic carbachol application was reduced by a prepulse of carbachol. The extra inhibition evoked by a prepulse disappeared exponentially with a time constant of 150-200 ms. 3. Barbiturates produce an increased rate of decay of nerve evoked endplate currents. Tne concentration and voltage dependence of the barbtiruate e.p.c. decay rates tally with the hypothesis that the increased rate of decay is due to block of active receptor-channel complexes by barbiturates with a rate constant of  10(6) M-1S-1. 4. Conductance changes produced by bath applied agonists were depressed by thiopentone, the effect becoming greater the higher the agonist concentration. This effect, and also the observation that the concentration of thiopentone required to depress the bath agonist response is much greater than the apparent dissociation constant for binding to active receptor-channel complexes calculated from kinetic measurements, suggest that the selectivity for binding to open receptor-channel complexes is very high. 5. Methyprylone, which is structurally similar to the barbiturates, is only a weak antagonist and shows no interpulse interaction. It was predicted that methyprylone should produce fast and slow components in the e.p.c. decay, and this prediction was verified. 6. In the presence of barbiturates large iontophoretic carbachol applications produce conductance changes which show fast and slow components. Under these conditions the effects of carbachol prepulses become complex. However the effects are qualitatively consistent with the notion that different components of the response are contributed by channels located at various distances from the iontophoretic pipette tip. 7. All the data agree with a model in which the channel has three stages: closed, open and blocked. Only open channels can block, and blocked channels can only open."}
{"id": "PMID:10433", "title": "Conductances, diffusion and streaming potentials in the rat proximal tubule.", "content": "1. Transtubular potential differences and specific resistances were measured in rat proximal tubules by means of single and double barrelled glass micro-electrodes. 2. Tip localization was made by observation of effective resistance changes measured with double barrelled micro-electrodes upon passage of oil droplets, and by perfusion with choline C1. 3. Mean early proximal p.d.s. of the order of -1 to -2 mV,  and late values of +0-5 to +1mV were found. Mean specific resistances ranged from 12 to 15 omega cm2. 4. Diffusion potentials and single ion relative conductances were evaluated, perfusing the lumen with solutions differing only with respect to one salt concentration. Na and K conductances were similar and greater than those of C1. 5. Luminal and peritubular perfusions with hypotonic solutions showed the occurrence of streaming potentials in this structure suggesting the existence of pores lined with negative charges. The effective diameter of these pores appeared to be reduced by hypotonic perfusion, as evidenced by a significant increase in resistance, indicating that the main ion path across this structure is represented by intercellular spaces.", "contents": "Conductances, diffusion and streaming potentials in the rat proximal tubule. 1. Transtubular potential differences and specific resistances were measured in rat proximal tubules by means of single and double barrelled glass micro-electrodes. 2. Tip localization was made by observation of effective resistance changes measured with double barrelled micro-electrodes upon passage of oil droplets, and by perfusion with choline C1. 3. Mean early proximal p.d.s. of the order of -1 to -2 mV,  and late values of +0-5 to +1mV were found. Mean specific resistances ranged from 12 to 15 omega cm2. 4. Diffusion potentials and single ion relative conductances were evaluated, perfusing the lumen with solutions differing only with respect to one salt concentration. Na and K conductances were similar and greater than those of C1. 5. Luminal and peritubular perfusions with hypotonic solutions showed the occurrence of streaming potentials in this structure suggesting the existence of pores lined with negative charges. The effective diameter of these pores appeared to be reduced by hypotonic perfusion, as evidenced by a significant increase in resistance, indicating that the main ion path across this structure is represented by intercellular spaces."}
{"id": "PMID:10434", "title": "Some aspects of foetal and uteroplacental metabolism in cows with indwelling umbilical and uterine vascular catheters.", "content": "1. The experiments were carried out on conscious pregnant Jersey cows with intravascular catheters implanted during late gestation in umbilical and uterine vessels. All but three of fifteen animals delivered live healthy calves. 2. Rountine daily analyses were made of blood gas tensions, pH and packed cell volume in foetal and maternal blood; plasma concentrations of glucose, fructose, lactate and urea were also determined. Measurements of plasma free fatty acids and blood acetate concentrations were made less frequently. Foetal heart rate and arterial blood pressure were recorded in animals with an umbilical arterial catheter. 3. The concentration differences between foetal and maternal blood or plasma in glucose, urea and acetate were measured in fifteen animals. The maternal-to-foetal glucose and acetate gradients across the placenta were high while the foetal-to-maternal plasma urea differences were small. 4. In those animals with patent arterial and venous catheters, uterine and umbilical blood flows were measured together with the arteriovenous differences in 02, glucose, acetate and lactate so that rates of foetal and uterine consumption could be estimated. The rates of utilization of O2, glucose and acetate by the foetus were lower than the values for the whole uterus, while the uteroplacental metabolism of these substrates was very high. 5. Significant amounts of lactate, which appeared to be produced by the uteroplacental tissue, were utilized by the foetus; the remainder passed into the uterine venous blood. 6. The total substrate/O2 quotient for the foetus, calculated from the utilization of known metabolites, appeared to be greater than 1. Thus, in the calf some carbon accumulation from sources other than amino acids, the uptake of which was not measured, would seem to occur. These results and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep.", "contents": "Some aspects of foetal and uteroplacental metabolism in cows with indwelling umbilical and uterine vascular catheters. 1. The experiments were carried out on conscious pregnant Jersey cows with intravascular catheters implanted during late gestation in umbilical and uterine vessels. All but three of fifteen animals delivered live healthy calves. 2. Rountine daily analyses were made of blood gas tensions, pH and packed cell volume in foetal and maternal blood; plasma concentrations of glucose, fructose, lactate and urea were also determined. Measurements of plasma free fatty acids and blood acetate concentrations were made less frequently. Foetal heart rate and arterial blood pressure were recorded in animals with an umbilical arterial catheter. 3. The concentration differences between foetal and maternal blood or plasma in glucose, urea and acetate were measured in fifteen animals. The maternal-to-foetal glucose and acetate gradients across the placenta were high while the foetal-to-maternal plasma urea differences were small. 4. In those animals with patent arterial and venous catheters, uterine and umbilical blood flows were measured together with the arteriovenous differences in 02, glucose, acetate and lactate so that rates of foetal and uterine consumption could be estimated. The rates of utilization of O2, glucose and acetate by the foetus were lower than the values for the whole uterus, while the uteroplacental metabolism of these substrates was very high. 5. Significant amounts of lactate, which appeared to be produced by the uteroplacental tissue, were utilized by the foetus; the remainder passed into the uterine venous blood. 6. The total substrate/O2 quotient for the foetus, calculated from the utilization of known metabolites, appeared to be greater than 1. Thus, in the calf some carbon accumulation from sources other than amino acids, the uptake of which was not measured, would seem to occur. These results and the metabolic activity of the uterine tissues are discussed in relation to comparable findings in the sheep."}
{"id": "PMID:10435", "title": "Stimulation-induced factors which affect augmentation and potentiation of trasmitter release at the neuromuscular junction.", "content": "1. End-plate potentials (e.p.p.s) were recorded from frog sartorius neuromuscular junctions under conditions of decreased transmitter release to study the effect of repetitive stimulation on augmentation and potentiation of transmitter release. 2. The magnitudes and time constants of decay of augmentation and potentiation were determined both following a primary conditioning train and following an identical secondary conditioning train applied from 30 to 170 sec after the primary conditioning train. 3. The magnitude of augmentation following the secondary conditioning trains was increased over that following the primary conditioning trains even though augmentation, with a time constant of decay of about 7 sec, had decayed to insignificant levels before the onset of the secondary trains. This increase in augmentation was not due to a change in its rate of decay during the secondary trains. 4. The increased magnitude of augmentation can be described as arising from an expression factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-6 +/- 1-2 (S.D. of observation) (the magnitude of augmentation is increased 2-6 times) and decays approximately exponentially with a time constant of 90 +/- 50 (S.D. of observation) sec. The expression factor thus decays about ten times slower than augmentation. 5. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 2-8 +/- 1-0 (S.D. of observation) times increase in the magnitude of the expression factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 6. The expression factor, while increasing the magnitude of augmentation, had little or no effect on the magnitude of potentiation or on trasmitter release in the absence of augmentation. The expression factor decayed about twice as slowly as potentiation. 7. The time constants characterizing the decay of potentiation were greater following the secondary conditioning trains than following the primary conditioning trains. 8. The increased time constant for the decay of potentiation can be described as arising from a time constant factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-2 +/- 0-7 (S.D. of observation) (the time constant of potentiation is increased 2-2 times) and decays approximately exponentially with a time constant of 130 +/- 45 (S.D. of observation) sec. The time constant factor decayed about three times slower than potentiation. 9. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 1-6 +/- 0-8 (S.D. of observation) times increase in the magnitude of the time constant factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 10...", "contents": "Stimulation-induced factors which affect augmentation and potentiation of trasmitter release at the neuromuscular junction. 1. End-plate potentials (e.p.p.s) were recorded from frog sartorius neuromuscular junctions under conditions of decreased transmitter release to study the effect of repetitive stimulation on augmentation and potentiation of transmitter release. 2. The magnitudes and time constants of decay of augmentation and potentiation were determined both following a primary conditioning train and following an identical secondary conditioning train applied from 30 to 170 sec after the primary conditioning train. 3. The magnitude of augmentation following the secondary conditioning trains was increased over that following the primary conditioning trains even though augmentation, with a time constant of decay of about 7 sec, had decayed to insignificant levels before the onset of the secondary trains. This increase in augmentation was not due to a change in its rate of decay during the secondary trains. 4. The increased magnitude of augmentation can be described as arising from an expression factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-6 +/- 1-2 (S.D. of observation) (the magnitude of augmentation is increased 2-6 times) and decays approximately exponentially with a time constant of 90 +/- 50 (S.D. of observation) sec. The expression factor thus decays about ten times slower than augmentation. 5. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 2-8 +/- 1-0 (S.D. of observation) times increase in the magnitude of the expression factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 6. The expression factor, while increasing the magnitude of augmentation, had little or no effect on the magnitude of potentiation or on trasmitter release in the absence of augmentation. The expression factor decayed about twice as slowly as potentiation. 7. The time constants characterizing the decay of potentiation were greater following the secondary conditioning trains than following the primary conditioning trains. 8. The increased time constant for the decay of potentiation can be described as arising from a time constant factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-2 +/- 0-7 (S.D. of observation) (the time constant of potentiation is increased 2-2 times) and decays approximately exponentially with a time constant of 130 +/- 45 (S.D. of observation) sec. The time constant factor decayed about three times slower than potentiation. 9. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 1-6 +/- 0-8 (S.D. of observation) times increase in the magnitude of the time constant factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 10..."}
{"id": "PMID:10436", "title": "Gastric emptying of organic acids in the dog.", "content": "Test meals of 300 ml. of six different organic acids were instilled into the stomach of six healthy mongrel dogs. Citric, acetic, propionic, lactic, tartaric and succinic acid were given in 50, 100, 150, and 200 mN concentrations. 2. During the emptying process, the gastric contents were aspirated and immediately re-instilled at 10 min intervals, and the following parameters were recorded: volume, concentration of the organic anion, pH, hydrogen ion concentration and osmolarity. 3. By multiple stepwise regression analysis, the combination of parameters which most effectively determines gastric emptying rate was found to be: concentration of the organic anion, followed by intragastric volume and number of previous test meals given on the same day. These three parameters appear in the equation for gastric emptying rate in which the individual characteristic of each acid is expressed by a constant. 4. Among the various acids, inhibition of emptying rate increases with rising number of carboxylic groups of the acid and its molecular weight. 5. After proximal gastric vagotomy, emptying rate of organic acids is independent of volume, and emptying approaches an exponential pattern. 6. A model for gastric emptying of organic acids with at least three different receptors is proposed: one for the structure of the organic acid, one for concentration and one for intragastric volume.", "contents": "Gastric emptying of organic acids in the dog. Test meals of 300 ml. of six different organic acids were instilled into the stomach of six healthy mongrel dogs. Citric, acetic, propionic, lactic, tartaric and succinic acid were given in 50, 100, 150, and 200 mN concentrations. 2. During the emptying process, the gastric contents were aspirated and immediately re-instilled at 10 min intervals, and the following parameters were recorded: volume, concentration of the organic anion, pH, hydrogen ion concentration and osmolarity. 3. By multiple stepwise regression analysis, the combination of parameters which most effectively determines gastric emptying rate was found to be: concentration of the organic anion, followed by intragastric volume and number of previous test meals given on the same day. These three parameters appear in the equation for gastric emptying rate in which the individual characteristic of each acid is expressed by a constant. 4. Among the various acids, inhibition of emptying rate increases with rising number of carboxylic groups of the acid and its molecular weight. 5. After proximal gastric vagotomy, emptying rate of organic acids is independent of volume, and emptying approaches an exponential pattern. 6. A model for gastric emptying of organic acids with at least three different receptors is proposed: one for the structure of the organic acid, one for concentration and one for intragastric volume."}
{"id": "PMID:10439", "title": "Evaluation of analgesic action and efficacy of antirheumatic drugs. Study of 10 drugs in 684 patients with rheumatoid arthritis.", "content": "A single-blind non-crossover method for assessing the potential effectiveness of antirheumatic drugs has been described. The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial. In addition, the mean number of days withdrawn and patients' satisfaction rating are measured. The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials. Ten antirheumatic medications were evaluated using this technique in 684 patients with rheumatoid arthritis, and the results are in agreement with those of previous studies using standard clinical methods. The new method is simple, rapid in performance, economical in terms of cost and time, and has been shown to be sensitive and reproducible. The results indicate that there are no significant differences in efficacy between the currently available non-steroidal, anti-inflammatory analgesic drugs, in the treatment of rheumatoid arthritis.", "contents": "Evaluation of analgesic action and efficacy of antirheumatic drugs. Study of 10 drugs in 684 patients with rheumatoid arthritis. A single-blind non-crossover method for assessing the potential effectiveness of antirheumatic drugs has been described. The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial. In addition, the mean number of days withdrawn and patients' satisfaction rating are measured. The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials. Ten antirheumatic medications were evaluated using this technique in 684 patients with rheumatoid arthritis, and the results are in agreement with those of previous studies using standard clinical methods. The new method is simple, rapid in performance, economical in terms of cost and time, and has been shown to be sensitive and reproducible. The results indicate that there are no significant differences in efficacy between the currently available non-steroidal, anti-inflammatory analgesic drugs, in the treatment of rheumatoid arthritis."}
{"id": "PMID:10441", "title": "Sympathomimetic amines having a carbostyril nucleus.", "content": "A series of new sympathomimetic amines containing an 8-hydroxycarbostyril moiety was synthesized. These compounds probably exist as resonance hybrids having two acidic hydrogen atoms in locations approximating to those of the hydroxyl groups of catechol-containing adrenergic agents. In an in vitro test, many of these compounds showed potent activity for relaxation of guinea pig tracheal smooth muscle. One of the compounds was 24 000 times more potent than isoproterenol. Their actions on cardiac muscle were also examined in vitro by measuring increase in the beating rate of the right atria of guinea pigs. Several of the compounds appeared to be beta-selective. Some of the compounds seem suitable for use as bronchodilators. The structure-activity relationships of these compounds were discussed in comparison with those of catecholamines.", "contents": "Sympathomimetic amines having a carbostyril nucleus. A series of new sympathomimetic amines containing an 8-hydroxycarbostyril moiety was synthesized. These compounds probably exist as resonance hybrids having two acidic hydrogen atoms in locations approximating to those of the hydroxyl groups of catechol-containing adrenergic agents. In an in vitro test, many of these compounds showed potent activity for relaxation of guinea pig tracheal smooth muscle. One of the compounds was 24 000 times more potent than isoproterenol. Their actions on cardiac muscle were also examined in vitro by measuring increase in the beating rate of the right atria of guinea pigs. Several of the compounds appeared to be beta-selective. Some of the compounds seem suitable for use as bronchodilators. The structure-activity relationships of these compounds were discussed in comparison with those of catecholamines."}
{"id": "PMID:10444", "title": "Fusion in phospholipid spherical membranes. II. Effect of cholesterol, divalent ions and pH.", "content": "Effect of cholesterol, divalent ions and pH on spherical bilayer membrane fusion was studied as a function of increasing temperature. Spherical bilayer membranes were composed of natural [phosphatidylcholine (PC) and phosphatidylserine (PS)] as well as synthetic (dipalmitoyl-PC, dimyristoyl-PC and dioleoyl-PC) phospholipids. Incorporation of cholesterol into the membrane (33% by weight) suppressed the fusion temperature and also greatly reduced the percentage of membrane fusion. The presence of 1 mM divalent ions (Ca++, Mg++ or Mn++) on both sides or one side of the PC membrane did not affect appreciably its fusion characteristic with temperature, but the PS membrane fusion with temperature was greatly enhanced by the presence of divalent ions. The variation of pH of the environmental solution in the range of 5.5 approximately 7.0 did not affect the membrane fusion characteristic. However, at pH 8.5, the fusion with respect to temperature was shifted toward the lower temperature by approximately 3degreesC for PC and PS membranes, and at pH 3.0 the opposite situation was observed as the fusion temperature was increased by 6degreesC for PS membranes and by 4degreesC for PC membranes The results seem to indicate that membrane fluidity and structural instability in the bilayer are important for membrane fusion to occur.", "contents": "Fusion in phospholipid spherical membranes. II. Effect of cholesterol, divalent ions and pH. Effect of cholesterol, divalent ions and pH on spherical bilayer membrane fusion was studied as a function of increasing temperature. Spherical bilayer membranes were composed of natural [phosphatidylcholine (PC) and phosphatidylserine (PS)] as well as synthetic (dipalmitoyl-PC, dimyristoyl-PC and dioleoyl-PC) phospholipids. Incorporation of cholesterol into the membrane (33% by weight) suppressed the fusion temperature and also greatly reduced the percentage of membrane fusion. The presence of 1 mM divalent ions (Ca++, Mg++ or Mn++) on both sides or one side of the PC membrane did not affect appreciably its fusion characteristic with temperature, but the PS membrane fusion with temperature was greatly enhanced by the presence of divalent ions. The variation of pH of the environmental solution in the range of 5.5 approximately 7.0 did not affect the membrane fusion characteristic. However, at pH 8.5, the fusion with respect to temperature was shifted toward the lower temperature by approximately 3degreesC for PC and PS membranes, and at pH 3.0 the opposite situation was observed as the fusion temperature was increased by 6degreesC for PS membranes and by 4degreesC for PC membranes The results seem to indicate that membrane fluidity and structural instability in the bilayer are important for membrane fusion to occur."}
{"id": "PMID:10447", "title": "Properties of two isolated antigens associated with bovine leukemia virus infection.", "content": "We isolated an ether-resistant internal antigen and an ether-sensitive antigen previously described in relation to bovine leukemia virus infection. These two antigens have now been isolated by isoelectric focusing and concanavalin A affinity chromatography, respectively. The ether-resistant antigen exhibited isoelectric heterogeneity with a major peak at pH 7.2 and a minor peak at pH 6.2. Its molecular weight, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was 23,000 (p23), and it gave a sedimentation value of 2.3s. For material containing ether-sensitive antigen, analyzed by SDS-PAGE, protein staining revealed four components with molecular weights of 18,000, 25,000, 45,000, and 55,000. Two of these [45,000 (gp45) and 55,000 (gp55)] were stained by periodic acid-Schiff reagent. Isoelectric point and sedimentation value of the major glycoprotein (gp45) were pH 5.0 and 3.4s, respectively; no immunologic cross-reactivity was found between p23 and glycoprotein antigen.", "contents": "Properties of two isolated antigens associated with bovine leukemia virus infection. We isolated an ether-resistant internal antigen and an ether-sensitive antigen previously described in relation to bovine leukemia virus infection. These two antigens have now been isolated by isoelectric focusing and concanavalin A affinity chromatography, respectively. The ether-resistant antigen exhibited isoelectric heterogeneity with a major peak at pH 7.2 and a minor peak at pH 6.2. Its molecular weight, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was 23,000 (p23), and it gave a sedimentation value of 2.3s. For material containing ether-sensitive antigen, analyzed by SDS-PAGE, protein staining revealed four components with molecular weights of 18,000, 25,000, 45,000, and 55,000. Two of these [45,000 (gp45) and 55,000 (gp55)] were stained by periodic acid-Schiff reagent. Isoelectric point and sedimentation value of the major glycoprotein (gp45) were pH 5.0 and 3.4s, respectively; no immunologic cross-reactivity was found between p23 and glycoprotein antigen."}
{"id": "PMID:10448", "title": "Glutathione and gamma glutamyl transpeptidase in rat liver during chemical carcinogenesis.", "content": "Continued administration of several hepatocarcinogens led to an increase in the concentration of glutathione (GSH) in the livers of intact, but not of hypophysectomized or adrenalectomized rats. The concentration of GSH remained high untill the development of hyperplastic nodules. Subsequently, the concentration of GSH dropped to the normal level or below. A single dose of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) produced an increase of GSH which, within a certain range, depended upon the amount of the carcinogen. In well differentiated, slowly growing hepatomas, the concentration of GSH approached the level in normal adult rat liver. On the other hand, in nondifferentiated and rapidly growing hepatomas, GSH was only 30-40% of that in normal liver. The activity of gamma-glutamyl transpeptidase (GTase) increased within 24-48 hours after a single large dose of 3'-Me-DAB. Continued feeding of 3'-Me-DAB led to an exponential increase of GTase. During hepatocarcinogenesis, the level of GTase activity corresponded to the degree and size of pathologic changes produced in rat liver. Chloramphenicol partially inhibited the increase of GTase induced by 2-acetylaminofluorene. Pretreatment with 3-methylcholanthrene partially inhibited the increase of GTase that had been induced by a single dose of 3'-Me-DAB. Puromycin partially inhibited the increase of GTase induced by several doses of dimethylnitrosamine. These observations indicated a close connection between the activation of GTase and chemical carcinogenesis in rat liver. Measurements of GTase activity in 12 Morris hepatomas supported this conclusion; their GTase levels were greatly elevated compared with that in normal adult rat liver.", "contents": "Glutathione and gamma glutamyl transpeptidase in rat liver during chemical carcinogenesis. Continued administration of several hepatocarcinogens led to an increase in the concentration of glutathione (GSH) in the livers of intact, but not of hypophysectomized or adrenalectomized rats. The concentration of GSH remained high untill the development of hyperplastic nodules. Subsequently, the concentration of GSH dropped to the normal level or below. A single dose of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) produced an increase of GSH which, within a certain range, depended upon the amount of the carcinogen. In well differentiated, slowly growing hepatomas, the concentration of GSH approached the level in normal adult rat liver. On the other hand, in nondifferentiated and rapidly growing hepatomas, GSH was only 30-40% of that in normal liver. The activity of gamma-glutamyl transpeptidase (GTase) increased within 24-48 hours after a single large dose of 3'-Me-DAB. Continued feeding of 3'-Me-DAB led to an exponential increase of GTase. During hepatocarcinogenesis, the level of GTase activity corresponded to the degree and size of pathologic changes produced in rat liver. Chloramphenicol partially inhibited the increase of GTase induced by 2-acetylaminofluorene. Pretreatment with 3-methylcholanthrene partially inhibited the increase of GTase that had been induced by a single dose of 3'-Me-DAB. Puromycin partially inhibited the increase of GTase induced by several doses of dimethylnitrosamine. These observations indicated a close connection between the activation of GTase and chemical carcinogenesis in rat liver. Measurements of GTase activity in 12 Morris hepatomas supported this conclusion; their GTase levels were greatly elevated compared with that in normal adult rat liver."}
{"id": "PMID:10449", "title": "Cyclic nucleotides in the regulation of expression of differentiated functions in neuroblastoma cells.", "content": "Adenosine 3',5'-cyclic monophosphate (cAMP) may be one of the important factors in regulating the expression of many differentiated functions in neuroblastoma cells, but some of these functions can be induced by agents that do not increase the intracellular level of cAMP. An elevation of the intracellular level of guanosine 3',5'-cyclic monophosphate (cGMP) neither induced differentiation nor antagonized the effects of cAMP. Neuroblastoma cells increased the level of cAMP-binding proteins during differentiation, whereas glial cells and L-cells did not. This might have accounted in part for an increase in the intracellular level of cAMP even in the presence of high phosphodiesterase activity in neuroblastoma cells, since the protein-bound with the same proteins, but cAMP had about 10 times higher affinity than did cGMP. cAMP promoted the organization of microtubules and microfilaments necessary for the expression of differentiated phenotypes. The extension of neurites required the synthesis of new protein, but it did not need the synthesis of new RNA. cAMP induced differentiation in neuroblastoma cells by increasing the expression of some genetic information while suppressing the expression of others; e.g., the activities of neural enzymes increased, whereas the synthesis of histone and the phosphorylation of H1-histone markedly decreased in differentiated cells. A hypothesis was offered: An increase in cAMP phosphodiesterase activity as a result of mutation in the regulatory gene for phosphodiesterase in a single, or group of, dividing nerve cell(s) is the primary lesion that leads to malignancy. Based on the concept that selective cytocytoxic drugs should be used with agents that cause differentiation, a new therapeutic approach was suggested for the treatment of neuroblastoma. This involved administration of sodium butyrate followed by L-DOPA or prostaglandin E1 in the presence of cAMP phosphodiesterase inhibitor followed by the less immunosuppressive vincristine and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide.", "contents": "Cyclic nucleotides in the regulation of expression of differentiated functions in neuroblastoma cells. Adenosine 3',5'-cyclic monophosphate (cAMP) may be one of the important factors in regulating the expression of many differentiated functions in neuroblastoma cells, but some of these functions can be induced by agents that do not increase the intracellular level of cAMP. An elevation of the intracellular level of guanosine 3',5'-cyclic monophosphate (cGMP) neither induced differentiation nor antagonized the effects of cAMP. Neuroblastoma cells increased the level of cAMP-binding proteins during differentiation, whereas glial cells and L-cells did not. This might have accounted in part for an increase in the intracellular level of cAMP even in the presence of high phosphodiesterase activity in neuroblastoma cells, since the protein-bound with the same proteins, but cAMP had about 10 times higher affinity than did cGMP. cAMP promoted the organization of microtubules and microfilaments necessary for the expression of differentiated phenotypes. The extension of neurites required the synthesis of new protein, but it did not need the synthesis of new RNA. cAMP induced differentiation in neuroblastoma cells by increasing the expression of some genetic information while suppressing the expression of others; e.g., the activities of neural enzymes increased, whereas the synthesis of histone and the phosphorylation of H1-histone markedly decreased in differentiated cells. A hypothesis was offered: An increase in cAMP phosphodiesterase activity as a result of mutation in the regulatory gene for phosphodiesterase in a single, or group of, dividing nerve cell(s) is the primary lesion that leads to malignancy. Based on the concept that selective cytocytoxic drugs should be used with agents that cause differentiation, a new therapeutic approach was suggested for the treatment of neuroblastoma. This involved administration of sodium butyrate followed by L-DOPA or prostaglandin E1 in the presence of cAMP phosphodiesterase inhibitor followed by the less immunosuppressive vincristine and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide."}
{"id": "PMID:10450", "title": "Catecholamine metabolism in neuroblastoma.", "content": "Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.", "contents": "Catecholamine metabolism in neuroblastoma. Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor."}
{"id": "PMID:10451", "title": "Exonuclease associated with bacteriophage T5-Induced DNA polymerase.", "content": "T-5-induced DNA polymerase has been shown to possess a 3' leads to 5'-exonucleolytic activity. The exonuclease acts on both native and denatured DNA, but the apparent rate of degradation of denatured DNA is about five times faster than that for native DNA. The enzyme appears to act only on 3'-OH ends and produces mainly 5'-dNMP's. Like polymerase activity, exonuclease activity shows a pH optimum around 8.6. Mg2+, dithiothreitol, and N-ethylmaleimide had identical effects on both the activities. Nicked DNA was almost totally protected from exonuclease action under synthetic conditions, i.e., in the presence of 4dNTP's. Denatured DNA was partly degraded in the early phase of incubation with 4dNTP's, presumably due to unhybridized tails at the 3'-OH primer ends. However, the exonuclease activity was operative in both cases under synthetic conditions, as evidenced by template-dependent conversion of [3H]dTTP to [3H]dTMP.", "contents": "Exonuclease associated with bacteriophage T5-Induced DNA polymerase. T-5-induced DNA polymerase has been shown to possess a 3' leads to 5'-exonucleolytic activity. The exonuclease acts on both native and denatured DNA, but the apparent rate of degradation of denatured DNA is about five times faster than that for native DNA. The enzyme appears to act only on 3'-OH ends and produces mainly 5'-dNMP's. Like polymerase activity, exonuclease activity shows a pH optimum around 8.6. Mg2+, dithiothreitol, and N-ethylmaleimide had identical effects on both the activities. Nicked DNA was almost totally protected from exonuclease action under synthetic conditions, i.e., in the presence of 4dNTP's. Denatured DNA was partly degraded in the early phase of incubation with 4dNTP's, presumably due to unhybridized tails at the 3'-OH primer ends. However, the exonuclease activity was operative in both cases under synthetic conditions, as evidenced by template-dependent conversion of [3H]dTTP to [3H]dTMP."}
{"id": "PMID:10452", "title": "Structural proteins of polyoma virus: proteolytic degradation of virion proteins by exogenous and by virion-associated proteases.", "content": "A model has previously been proposed for the genetic relatedness of the structural proteins of polyoma virus, based upon similarities in the peptide maps of the major capsid protein VP1 with the virion proteins VP2 and VP3. Newer evidence suggests that this model is incorrect, and that protein VP1 is a product of one viral gene and that the multiple components of VP2 and VP3 are products of a second viral gene. Two-dimensional peptide maps of several preparations of polyoma purified separately from four separate infected-cell lysates has shown a variable content of VP1 peptides in proteins VP2 and VP3, with some preparations being free of detectable VP1 material in VP2 and VP3. An alternative explanation for the presence of VP1 peptides in the regions of VP2 and VP3 of some polyoma preparations involves the cleavage of proteins of polyoma virions during exposure to proteolytic enzymes in lysates of infected cells or to endogenous proteolytic activity of virions. Prolonged incubation of infected-cell lysates at 37 degrees C leads to an increase in the amount of 86,000-dalton dimer of VP1, a decrease in the relative amount of VP1, a decrease in or a loss of the lower band of VP2, and the appearance of a new major protein band of approximately 29,000 daltons. Two-dimensional peptide maps of the new 29,000-dalton protein show that it contains some VP1 peptides, indicating that this protein is derived from proteolytic cleavage of VP1. In addition, extensively purified polyoma virus contains a proteolytic activity that can be activated during disruption of the virus with 0.2 M Na2CO3-NaHCO3 (pH 10.6) in the presence of 5 X 10(-3) M dithiothreitol.", "contents": "Structural proteins of polyoma virus: proteolytic degradation of virion proteins by exogenous and by virion-associated proteases. A model has previously been proposed for the genetic relatedness of the structural proteins of polyoma virus, based upon similarities in the peptide maps of the major capsid protein VP1 with the virion proteins VP2 and VP3. Newer evidence suggests that this model is incorrect, and that protein VP1 is a product of one viral gene and that the multiple components of VP2 and VP3 are products of a second viral gene. Two-dimensional peptide maps of several preparations of polyoma purified separately from four separate infected-cell lysates has shown a variable content of VP1 peptides in proteins VP2 and VP3, with some preparations being free of detectable VP1 material in VP2 and VP3. An alternative explanation for the presence of VP1 peptides in the regions of VP2 and VP3 of some polyoma preparations involves the cleavage of proteins of polyoma virions during exposure to proteolytic enzymes in lysates of infected cells or to endogenous proteolytic activity of virions. Prolonged incubation of infected-cell lysates at 37 degrees C leads to an increase in the amount of 86,000-dalton dimer of VP1, a decrease in the relative amount of VP1, a decrease in or a loss of the lower band of VP2, and the appearance of a new major protein band of approximately 29,000 daltons. Two-dimensional peptide maps of the new 29,000-dalton protein show that it contains some VP1 peptides, indicating that this protein is derived from proteolytic cleavage of VP1. In addition, extensively purified polyoma virus contains a proteolytic activity that can be activated during disruption of the virus with 0.2 M Na2CO3-NaHCO3 (pH 10.6) in the presence of 5 X 10(-3) M dithiothreitol."}
{"id": "PMID:10455", "title": "Purification and properties of glucose-6-phosphate dehydrogenase from Bacillus subtilis spores.", "content": "Glucose-6-phosphate dehydrogenase [D-glucose-6-phosphate: NADP oxidoreductase, EC. 1. 1. 1. 49] obtained from spores of Bacillus subtilis PCI 219 strain was partially purified by filtration on Sephadex G-200, ammonium sulfate fractionation and chromatography on DEAE-Sephadex A-25 (about 54-fold). The optimum pH for stability of this enzyme was about 6.3 and the optimum pH for the reaction about 8.3. The apparent Km values of the enzyme were 5.7 X 10(-4) M for glucose-6-phosphate and 2.4 X 10(-4) M for nicotinamide adenine dinucleotide phosphate (NADP). The isoelectric point was about pH 3.9. The enzyme activity was unaffected by the addition of Mg++ or Ca++. The inactive glucose-6-phosphate dehydrogenase obtained from the spores heated at 85 C for 30 min was not reactivated by the addition of ethylenediaminetetraacetic acid, dipicolinic acid or some salts unlike inactive glucose dehydrogenase.", "contents": "Purification and properties of glucose-6-phosphate dehydrogenase from Bacillus subtilis spores. Glucose-6-phosphate dehydrogenase [D-glucose-6-phosphate: NADP oxidoreductase, EC. 1. 1. 1. 49] obtained from spores of Bacillus subtilis PCI 219 strain was partially purified by filtration on Sephadex G-200, ammonium sulfate fractionation and chromatography on DEAE-Sephadex A-25 (about 54-fold). The optimum pH for stability of this enzyme was about 6.3 and the optimum pH for the reaction about 8.3. The apparent Km values of the enzyme were 5.7 X 10(-4) M for glucose-6-phosphate and 2.4 X 10(-4) M for nicotinamide adenine dinucleotide phosphate (NADP). The isoelectric point was about pH 3.9. The enzyme activity was unaffected by the addition of Mg++ or Ca++. The inactive glucose-6-phosphate dehydrogenase obtained from the spores heated at 85 C for 30 min was not reactivated by the addition of ethylenediaminetetraacetic acid, dipicolinic acid or some salts unlike inactive glucose dehydrogenase."}
{"id": "PMID:10456", "title": "A new analgesic testing method using ultrasonic stimulation. I. Effects of narcotic and nonnarcotic analgesics.", "content": "A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in mice has been designed. The method had the advantage of precision, simplicity of technique, rapidity of measurement, and the fact that the stimuli is innocuous upon repeated application. The nature of the senstaions induced by ultrasonic stimulus is somewhat like that felt with a prick type of pain. Pentazocine (30, 100, 150 mg/kg i.p.) aminopyrine (15,50, 100, 150 mg/kg i.p.), phenacetin (100,150, 200, 250 mg/kg i.p.) sodium salicylate (150, 200, 250 mg/kg i.p.) and other antipyretic analgesics were active in a wide range of doses indicating that this technique is sensitive to the narcotic antagonist and to the weak analgesics as well as to the narcotic analgesics as well as to the narcotic analgesics such as morphine (2.5, 5, 10, 15 mg/kg i.p.), codeine (10, 20, 25, 30, 50 mg/kg i.p.) and pethidine (5,10, 15, 20, 25 mg/kg i.p.). The ultrasonic method is, therefore, applicable in screening procedures when attempting to evaluate the analgesic potency of a wide variety of chemical agents.", "contents": "A new analgesic testing method using ultrasonic stimulation. I. Effects of narcotic and nonnarcotic analgesics. A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in mice has been designed. The method had the advantage of precision, simplicity of technique, rapidity of measurement, and the fact that the stimuli is innocuous upon repeated application. The nature of the senstaions induced by ultrasonic stimulus is somewhat like that felt with a prick type of pain. Pentazocine (30, 100, 150 mg/kg i.p.) aminopyrine (15,50, 100, 150 mg/kg i.p.), phenacetin (100,150, 200, 250 mg/kg i.p.) sodium salicylate (150, 200, 250 mg/kg i.p.) and other antipyretic analgesics were active in a wide range of doses indicating that this technique is sensitive to the narcotic antagonist and to the weak analgesics as well as to the narcotic analgesics as well as to the narcotic analgesics such as morphine (2.5, 5, 10, 15 mg/kg i.p.), codeine (10, 20, 25, 30, 50 mg/kg i.p.) and pethidine (5,10, 15, 20, 25 mg/kg i.p.). The ultrasonic method is, therefore, applicable in screening procedures when attempting to evaluate the analgesic potency of a wide variety of chemical agents."}
{"id": "PMID:10457", "title": "Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (III). Functional antagonism between beta-mimetics and spasmogens.", "content": "New equations which can explain the following characteristic phenomena in the functional antagonism between isoproterenol (ISO) and spasmogens in guinea-pig trachea are proposed: (1) The amplitude of relaxation of the muscle induced by ISO varied depending on the concentration of a spasmogen used (histamine or carbachol). (2) The dose-response curves for the relaxation by ISO shifted to the right in a parallel manner as the concentration of the spasmogen increased, and became stationary at high concentrations of the spasmogen. (3) The slope of the dose-response curve became steeper with increasing concentrations of the spasmogen. When the saturable uptake process of ISO was taken into consideration, a satisfactory parallel was seen between the theoretical dose-response curves and the present experimental results.", "contents": "Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (III). Functional antagonism between beta-mimetics and spasmogens. New equations which can explain the following characteristic phenomena in the functional antagonism between isoproterenol (ISO) and spasmogens in guinea-pig trachea are proposed: (1) The amplitude of relaxation of the muscle induced by ISO varied depending on the concentration of a spasmogen used (histamine or carbachol). (2) The dose-response curves for the relaxation by ISO shifted to the right in a parallel manner as the concentration of the spasmogen increased, and became stationary at high concentrations of the spasmogen. (3) The slope of the dose-response curve became steeper with increasing concentrations of the spasmogen. When the saturable uptake process of ISO was taken into consideration, a satisfactory parallel was seen between the theoretical dose-response curves and the present experimental results."}
{"id": "PMID:10458", "title": "Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (IV). Influence of functional antagonism by spasmogens.", "content": "A new theory is presented to describe the effect of functional antagonism on the competitive antagonism between adrenergic beta-mimetics and beta-blockers. According to this theory the shape of the log (dose ratio-1) vs.--log [B] curve and the apparent pA2 value in competitive antagonism should be affected by functional antagonism when the agonist is taken up by the saturable uptake process, and this was experimentally confirmed. The competitive antagonism between isoproterenol (ISO) and propranolol (Prop) was influenced by the functional antagonism between ISO and spasmogens (histamine and carbachol). The log (dose ratio-1) vs. --log [B] curve is ISO-Prop competitive antagonism was shifted variously depending on the concentration of a spasmogen used. Theoretical predictions and experimental results were in good parallel.", "contents": "Studies on the mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (IV). Influence of functional antagonism by spasmogens. A new theory is presented to describe the effect of functional antagonism on the competitive antagonism between adrenergic beta-mimetics and beta-blockers. According to this theory the shape of the log (dose ratio-1) vs.--log [B] curve and the apparent pA2 value in competitive antagonism should be affected by functional antagonism when the agonist is taken up by the saturable uptake process, and this was experimentally confirmed. The competitive antagonism between isoproterenol (ISO) and propranolol (Prop) was influenced by the functional antagonism between ISO and spasmogens (histamine and carbachol). The log (dose ratio-1) vs. --log [B] curve is ISO-Prop competitive antagonism was shifted variously depending on the concentration of a spasmogen used. Theoretical predictions and experimental results were in good parallel."}
{"id": "PMID:10460", "title": "HLA antigens in arterial occlusive diseases in Japan.", "content": "Using a NIH standard lymphocytotoxicity test, a possible Japanese specific HLA antigen, HLA-BJW 22.2 was identified in 17 out of 48 patients with thromboangiitis obliterans (35.4 per cent), in 5 out of 15 patients with Takayasu's arteritis (33.3 per cent) and in 11 out of 113 normal controls (9.7 per cent). On the other hand, HLA-CWl was found in 4 out of 47 patients with arteriosclerosis obliterans (8.5 per cent) and in 41 out of 113 normal controls (36.3 per cent).", "contents": "HLA antigens in arterial occlusive diseases in Japan. Using a NIH standard lymphocytotoxicity test, a possible Japanese specific HLA antigen, HLA-BJW 22.2 was identified in 17 out of 48 patients with thromboangiitis obliterans (35.4 per cent), in 5 out of 15 patients with Takayasu's arteritis (33.3 per cent) and in 11 out of 113 normal controls (9.7 per cent). On the other hand, HLA-CWl was found in 4 out of 47 patients with arteriosclerosis obliterans (8.5 per cent) and in 41 out of 113 normal controls (36.3 per cent)."}
{"id": "PMID:10463", "title": "[Comparative evaluation of the clinical action of a series of beta-adrenergic blockaders].", "content": "A comparative clinical study of the efficacy of Benzoral, Trasicor, Viskene, Aptene, Eraldine and Inderal was conducted in the ischaemic heart disease patients. Their antiarrhythmic and antianginal effect was determined, as well as their optimum therapeutic dosages, the activity of their specific beta-adrenolytic properties, the effect of the drugs on the bronchi and the peripheral venous tone. Apart from the clinical study, electro- and polycardiography, functional pulmonary tests and the Schellong orthostatic test were used. All the drugs in question were found to produce a distinct specific beta-blocking effect. They are effective in cases of atrial and ventricular extrasystole, paroxysmal tachycardia, sinus tachycardia and tachyarrhythmic fibrillation, as well as for the prevention of anginal attacks and arrhythmic fibrillation. All the drugs produce a negative inotropic effect, Inderal--the strongest, Viskene and Benzoral--the weakest. All beta-blockers can impair bronchial patency in patients with bronchial obstruction. This effect is least pronounced with Eraldine that may be used as the drug of choice in such cases. In most cases the beta-blockers do not affect the peripheral venous tone, but in some cases they may reduce it.", "contents": "[Comparative evaluation of the clinical action of a series of beta-adrenergic blockaders]. A comparative clinical study of the efficacy of Benzoral, Trasicor, Viskene, Aptene, Eraldine and Inderal was conducted in the ischaemic heart disease patients. Their antiarrhythmic and antianginal effect was determined, as well as their optimum therapeutic dosages, the activity of their specific beta-adrenolytic properties, the effect of the drugs on the bronchi and the peripheral venous tone. Apart from the clinical study, electro- and polycardiography, functional pulmonary tests and the Schellong orthostatic test were used. All the drugs in question were found to produce a distinct specific beta-blocking effect. They are effective in cases of atrial and ventricular extrasystole, paroxysmal tachycardia, sinus tachycardia and tachyarrhythmic fibrillation, as well as for the prevention of anginal attacks and arrhythmic fibrillation. All the drugs produce a negative inotropic effect, Inderal--the strongest, Viskene and Benzoral--the weakest. All beta-blockers can impair bronchial patency in patients with bronchial obstruction. This effect is least pronounced with Eraldine that may be used as the drug of choice in such cases. In most cases the beta-blockers do not affect the peripheral venous tone, but in some cases they may reduce it."}
{"id": "PMID:10464", "title": "[Change in the central and regional (brain) hemodynamics in the treatment of hypertension using beta-adrenergic blockaders].", "content": "The haemodynamic parameters were studied dynamically by way of noninvasive techniques--tetrapolar thoracic rheography in the course of treatment of 48 patients with essential hypertension Stage IB and IIA urth beta-blocking agents Obsidan and Visken. It was found that as early as by the 5th day of therapy the stroke volume and heart rate decreased, the maximum fall being noted after 2-3 weeks of treatment. The reflex elevation of the total peripheral resistance was moderate, as a result of which a gradual reduction of the arterial pressure developed. The state of the cerebral circulation significantly improved in the course of the treatment (as shown by rheoencephalography) and the tone of the cerebral arteries decreased. After 2-3 weeks of beta-blockers therapy favourable shifts were observed in the response of the general and cerebral haemodynamics to the orthostatic test.", "contents": "[Change in the central and regional (brain) hemodynamics in the treatment of hypertension using beta-adrenergic blockaders]. The haemodynamic parameters were studied dynamically by way of noninvasive techniques--tetrapolar thoracic rheography in the course of treatment of 48 patients with essential hypertension Stage IB and IIA urth beta-blocking agents Obsidan and Visken. It was found that as early as by the 5th day of therapy the stroke volume and heart rate decreased, the maximum fall being noted after 2-3 weeks of treatment. The reflex elevation of the total peripheral resistance was moderate, as a result of which a gradual reduction of the arterial pressure developed. The state of the cerebral circulation significantly improved in the course of the treatment (as shown by rheoencephalography) and the tone of the cerebral arteries decreased. After 2-3 weeks of beta-blockers therapy favourable shifts were observed in the response of the general and cerebral haemodynamics to the orthostatic test."}
{"id": "PMID:10466", "title": "[Assay of carbromal and its main metabolite (2-ethyl-butyryl-urea) in biological fluids (author's transl)].", "content": "The materials mentioned above are reextracted from an ether solution by 2 N sodium hydroxide. The UV extinction of the aqueous layer at 232 nm and 30 degrees C is followed by means of a slave recorder. The original extinction is found by back-extrapolating to the time of re-extraction. It has to be corrected for the \"biological matrix\" by subtracting the extinction value after complete hydrolysis. Most interfering substances in the ether solution (carboxylic acids, barbiturates) may be removed previously by washing with aqueous buffers (pH 7.0 and 10.5).", "contents": "[Assay of carbromal and its main metabolite (2-ethyl-butyryl-urea) in biological fluids (author's transl)]. The materials mentioned above are reextracted from an ether solution by 2 N sodium hydroxide. The UV extinction of the aqueous layer at 232 nm and 30 degrees C is followed by means of a slave recorder. The original extinction is found by back-extrapolating to the time of re-extraction. It has to be corrected for the \"biological matrix\" by subtracting the extinction value after complete hydrolysis. Most interfering substances in the ether solution (carboxylic acids, barbiturates) may be removed previously by washing with aqueous buffers (pH 7.0 and 10.5)."}
{"id": "PMID:10467", "title": "Histamine H2-receptor antagonists and gastric acid secretion -- a progress report.", "content": "Histamine H2-receptor antagonists, including burimamide, metiamide and cimetidine, are effective antagonists of histamine-stimulated acid secretion from mammalian, avian or reptilian gastric mucosa. Acid secretion stimulated by gastrin or pentagastrin is also inhibited by these drugs, but there is disagreement about the effects of these drugs on acid secretion resulting from activation of acetylcholine receptors. Based on the pharmacological evidence possibilities of treatment by these drugs were discussed in cases with excessive stimulation of acid secretion due to high blood levels of histamine or gastrin. The positive results in several trials on Zollinger-Ellison syndrome and peptic ulcer were very impressive. Some practical problems have still to be solved, for example the appropriate phase for applying the drugs. The demonstrated clinical effectiveness, however, against peptic ulceration offers a clear alternative to surgery for many patients.", "contents": "Histamine H2-receptor antagonists and gastric acid secretion -- a progress report. Histamine H2-receptor antagonists, including burimamide, metiamide and cimetidine, are effective antagonists of histamine-stimulated acid secretion from mammalian, avian or reptilian gastric mucosa. Acid secretion stimulated by gastrin or pentagastrin is also inhibited by these drugs, but there is disagreement about the effects of these drugs on acid secretion resulting from activation of acetylcholine receptors. Based on the pharmacological evidence possibilities of treatment by these drugs were discussed in cases with excessive stimulation of acid secretion due to high blood levels of histamine or gastrin. The positive results in several trials on Zollinger-Ellison syndrome and peptic ulcer were very impressive. Some practical problems have still to be solved, for example the appropriate phase for applying the drugs. The demonstrated clinical effectiveness, however, against peptic ulceration offers a clear alternative to surgery for many patients."}
{"id": "PMID:10470", "title": "[Selection of a urine preservative agent in relation to oxidative-catalytic methods of water regeneration].", "content": "Various chemicals were assayed as possible urine conservers to the used in space water reclamation systems. With respect to the antimicrobial activity and the quality of reclaimed water formalin at a concentration of 0.1% was selected as the best conserver. The reagent ensures urine preservation for 3 months.", "contents": "[Selection of a urine preservative agent in relation to oxidative-catalytic methods of water regeneration]. Various chemicals were assayed as possible urine conservers to the used in space water reclamation systems. With respect to the antimicrobial activity and the quality of reclaimed water formalin at a concentration of 0.1% was selected as the best conserver. The reagent ensures urine preservation for 3 months."}
{"id": "PMID:10478", "title": "[Hypoxia and polytrauma].", "content": "The importance of polytrauma and hypoxia, resp., is discussed by the authors with regard to the mortality and the common effect of these is analysed. It was found that in the mortality of the patients suffered polytraumatism the first place (59,4%) is taken by such lesions, in which simultaneous lesion of the skull and the thorax occurs. The values of the blood gas and the acid-base balance of the patients who had suffered polytraumatism, were examined in the 12th--24th hours proceding the death. It was found that whereas--using the possibilities of the intensive therapy--the values of pH, paCO2 and BE could be kept in a part of the cases between the physiological limits--the paO2 value was under the normal value in all cases--moreover 2/3 of the values fell into the domain between 40--60 mmHg--signifying severe hypoxia. On the basis of the analysis it may be presumed that in the process leading to death of the patients who had suffered polytraumatism the anoxic hypoxy plays considerable role. This is supported also by the earlier data published by the institute, according to which the mortality in itself high--33.8%--of polytraumatism increases to 71.4%, if it is associated hypoxy. Consequently the aim of the therapy must be to exert the greatest activity in order to prevent or to combat, resp., the anoxic hypoxy.", "contents": "[Hypoxia and polytrauma]. The importance of polytrauma and hypoxia, resp., is discussed by the authors with regard to the mortality and the common effect of these is analysed. It was found that in the mortality of the patients suffered polytraumatism the first place (59,4%) is taken by such lesions, in which simultaneous lesion of the skull and the thorax occurs. The values of the blood gas and the acid-base balance of the patients who had suffered polytraumatism, were examined in the 12th--24th hours proceding the death. It was found that whereas--using the possibilities of the intensive therapy--the values of pH, paCO2 and BE could be kept in a part of the cases between the physiological limits--the paO2 value was under the normal value in all cases--moreover 2/3 of the values fell into the domain between 40--60 mmHg--signifying severe hypoxia. On the basis of the analysis it may be presumed that in the process leading to death of the patients who had suffered polytraumatism the anoxic hypoxy plays considerable role. This is supported also by the earlier data published by the institute, according to which the mortality in itself high--33.8%--of polytraumatism increases to 71.4%, if it is associated hypoxy. Consequently the aim of the therapy must be to exert the greatest activity in order to prevent or to combat, resp., the anoxic hypoxy."}
{"id": "PMID:10479", "title": "[Classification and diagnosis of ankle injuries].", "content": "A new method for the classification of the injuries of the ankle is recommended by the author. The main types according to his classifixation are the following: pronation-flexion, pronation-extension, supination-extension, supination-flexion and supination-extension types. His classification is compared with Lauge-Hansen's and Weber's classification. Critical analysis of these two last classifications is given. The aim of the author's classification is to render help to the doctors for their every-days' curative work. The characteristic symptoms of the pronation and supination, resp., injuries are described. Attention is drawn to \"Weber's lace\"--this denomination is proposed by the author, since the first description is due to Weber. On the basis of the author's examinations described in his candidate's dissertation \"syndesmolysis trigonum\"--pathognostic for syndesmolysis--is dealt with. The \"reclined\" roentgenograms are dealt with. The so-called pronation reclined roentgenogram visualize the rupture of the deltoid ligament and the syndesmolysis in the same time. The sagittal reclined roentgenogram is dealth with separately, by means of which the \"table-drawer\" symptom may be produced.", "contents": "[Classification and diagnosis of ankle injuries]. A new method for the classification of the injuries of the ankle is recommended by the author. The main types according to his classifixation are the following: pronation-flexion, pronation-extension, supination-extension, supination-flexion and supination-extension types. His classification is compared with Lauge-Hansen's and Weber's classification. Critical analysis of these two last classifications is given. The aim of the author's classification is to render help to the doctors for their every-days' curative work. The characteristic symptoms of the pronation and supination, resp., injuries are described. Attention is drawn to \"Weber's lace\"--this denomination is proposed by the author, since the first description is due to Weber. On the basis of the author's examinations described in his candidate's dissertation \"syndesmolysis trigonum\"--pathognostic for syndesmolysis--is dealt with. The \"reclined\" roentgenograms are dealt with. The so-called pronation reclined roentgenogram visualize the rupture of the deltoid ligament and the syndesmolysis in the same time. The sagittal reclined roentgenogram is dealth with separately, by means of which the \"table-drawer\" symptom may be produced."}
{"id": "PMID:10480", "title": "[The effect of ligament calcification following syndesmolysis on pseudoarthrosis of the median malleolus].", "content": "The development of the false joint of the medial malleolus of 16 patients has been followed by the authors at the least for 13 years. It was found that in the cases, in which the fracture of the medial malleolus was concomitant with syndesmolysis, recovery of the false joint occured in the cases, in which in the place of the syndesmolysis calcification appeared, which brought the lateral cutting effect in the talo-crural joint to an end.", "contents": "[The effect of ligament calcification following syndesmolysis on pseudoarthrosis of the median malleolus]. The development of the false joint of the medial malleolus of 16 patients has been followed by the authors at the least for 13 years. It was found that in the cases, in which the fracture of the medial malleolus was concomitant with syndesmolysis, recovery of the false joint occured in the cases, in which in the place of the syndesmolysis calcification appeared, which brought the lateral cutting effect in the talo-crural joint to an end."}
{"id": "PMID:10481", "title": "[Conservative and surgical treatment of open fractures of the forearm].", "content": "On the basis of the 10 years' material of the Hugarian National Institute of Traumatology the possibilities of treatment of the open fractures of the forearm are discussed. It is stated by the authors that operative treatment of the open fractures of the forearm is more and more frequent, and--chiefly in the last time--the surgeon strives to obtain rigid internal fixation. If the individual and objective conditions of the internal fixation are not given or the operation seems risky for other reasons--intramedullary splinting--completing the conservative treatment--or wire fixation are the method of choice. In connection with fractures of different type the authors' method is discussed and a few cases are reported.", "contents": "[Conservative and surgical treatment of open fractures of the forearm]. On the basis of the 10 years' material of the Hugarian National Institute of Traumatology the possibilities of treatment of the open fractures of the forearm are discussed. It is stated by the authors that operative treatment of the open fractures of the forearm is more and more frequent, and--chiefly in the last time--the surgeon strives to obtain rigid internal fixation. If the individual and objective conditions of the internal fixation are not given or the operation seems risky for other reasons--intramedullary splinting--completing the conservative treatment--or wire fixation are the method of choice. In connection with fractures of different type the authors' method is discussed and a few cases are reported."}
{"id": "PMID:10477", "title": "Helix-coil stability constants for the naturally occurring amino acids in water. 11. Lysine parameters from random poly(hydroxybutylglutamine-co-L-lysine).", "content": "The synthesis and characterization of water-soluble random copolymers containing L-lysine with N5-(4-hydroxybutyl)-L-glutamine, and the thermally induced helix-coil transitions of these copolymers in water, are described. The incorporation of L-lysine was found to decrease the helix content of the polymers at neutral pH. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-lysine) in water were deduced from an analysis of the melting curves in the manner described in earlier papers. The computed values of s indicate that, in the temperature range of 0-60 degrees C, lysine has a tendency to destabilize helical sequences, this tendency being minimal at approximately 25 degrees C and increasing at lower and higher temperatures.", "contents": "Helix-coil stability constants for the naturally occurring amino acids in water. 11. Lysine parameters from random poly(hydroxybutylglutamine-co-L-lysine). The synthesis and characterization of water-soluble random copolymers containing L-lysine with N5-(4-hydroxybutyl)-L-glutamine, and the thermally induced helix-coil transitions of these copolymers in water, are described. The incorporation of L-lysine was found to decrease the helix content of the polymers at neutral pH. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-lysine) in water were deduced from an analysis of the melting curves in the manner described in earlier papers. The computed values of s indicate that, in the temperature range of 0-60 degrees C, lysine has a tendency to destabilize helical sequences, this tendency being minimal at approximately 25 degrees C and increasing at lower and higher temperatures."}
{"id": "PMID:10483", "title": "[Substitution of the frontal bone with silicon].", "content": "The good results obtained with silicon implants used in the frontal region are reported by the authors. After the correct primary treatment the reconstructive operations have been performed at the least 6 months after the lesion, if the environment of the defect was free from any reaction during this time. 14 implantations have been performed in 2 years. Satisfactory functional and cosmetic results were obtained and the implant was to be removed in no case.", "contents": "[Substitution of the frontal bone with silicon]. The good results obtained with silicon implants used in the frontal region are reported by the authors. After the correct primary treatment the reconstructive operations have been performed at the least 6 months after the lesion, if the environment of the defect was free from any reaction during this time. 14 implantations have been performed in 2 years. Satisfactory functional and cosmetic results were obtained and the implant was to be removed in no case."}
{"id": "PMID:10484", "title": "[Treatment of injuries of the penis and scrotum complicated by total skin loss].", "content": "In connection with two healed cases the free transplantation of semi-thick skin is recommended by the authors for the treatment of the above-mentioned injuries, on the basis of the following reasons: 1. The most ideal results may be expected from this method. 2. The objective conditions (dermatome, Humbey's knife, sponge etc.) age generally given. 3. The semi-thick skin plasty is one of the mostly used and well-known methods. 4. In the case of failure the method may be repeated or other method may be chosen. 5. Semi-thick skin plasty is the easiest way to observe the principle: \"Nil nocere\".", "contents": "[Treatment of injuries of the penis and scrotum complicated by total skin loss]. In connection with two healed cases the free transplantation of semi-thick skin is recommended by the authors for the treatment of the above-mentioned injuries, on the basis of the following reasons: 1. The most ideal results may be expected from this method. 2. The objective conditions (dermatome, Humbey's knife, sponge etc.) age generally given. 3. The semi-thick skin plasty is one of the mostly used and well-known methods. 4. In the case of failure the method may be repeated or other method may be chosen. 5. Semi-thick skin plasty is the easiest way to observe the principle: \"Nil nocere\"."}
{"id": "PMID:10485", "title": "[Acute arteria mesenterica superior syndrome caused by severe electric injury].", "content": "The case of acute arteria mesenterica superior syndrome--occurred in a boy aged 10, as rare complication of high voltage electro-trauma--is reported. The aetiology of the syndrome, as well as a possible new pathogenic factor are discussed. The clinical picture and the therapeutic principles are dealt with.", "contents": "[Acute arteria mesenterica superior syndrome caused by severe electric injury]. The case of acute arteria mesenterica superior syndrome--occurred in a boy aged 10, as rare complication of high voltage electro-trauma--is reported. The aetiology of the syndrome, as well as a possible new pathogenic factor are discussed. The clinical picture and the therapeutic principles are dealt with."}
{"id": "PMID:10486", "title": "[Substitution of an injured finger joint by silicone rubber prosthesis].", "content": "Between 1973 and the first semester of 1975, on the injured and destroyed digital articulation 27 patients have been operated on by means silicon rubber prosthesis of Swanson type. The prosthesis plasty and the field of its use are shortly resumed, pointing out the importance of its adaptation on the injured articulation. The operative technique is described, as well as the results obtained and the aspects of the evaluation are discussed. The results obtained with the silicon rubber prosthesis are very promising. In the case of failure arthrodesis may be performed at any time.", "contents": "[Substitution of an injured finger joint by silicone rubber prosthesis]. Between 1973 and the first semester of 1975, on the injured and destroyed digital articulation 27 patients have been operated on by means silicon rubber prosthesis of Swanson type. The prosthesis plasty and the field of its use are shortly resumed, pointing out the importance of its adaptation on the injured articulation. The operative technique is described, as well as the results obtained and the aspects of the evaluation are discussed. The results obtained with the silicon rubber prosthesis are very promising. In the case of failure arthrodesis may be performed at any time."}
{"id": "PMID:10487", "title": "[Phlebography of the talus following fracture and dislocation (preliminary report)].", "content": "After dislocation or dislocated fracture of the talus late arthrosis is a frequent complication, in which primary bone and cartilage damage play a role. For the demonstration and preclusion, resp., of the vascular damage phlebography performed 3--6 months after the injury is recommended by the authors--by means of which favourable initial experiences could be obtained.", "contents": "[Phlebography of the talus following fracture and dislocation (preliminary report)]. After dislocation or dislocated fracture of the talus late arthrosis is a frequent complication, in which primary bone and cartilage damage play a role. For the demonstration and preclusion, resp., of the vascular damage phlebography performed 3--6 months after the injury is recommended by the authors--by means of which favourable initial experiences could be obtained."}
{"id": "PMID:10490", "title": "Pharmacotherapy of myocardial ischemia.", "content": "The cornerstones of pharmacotherapy for myocardial ischemia are the nitrites and the beta-adrenergic blocking agents. These drugs not only inhibit cardiac mechanical activity (and therefore energy requirements) in a variety of ways but also redistribute available blood flow to the potentially ischemic segments of cardiac muscle. The least effective dose of nitroglycerin and the most tolerated (or blocking) dose of propranolol provide the optimum in management. There is increasing evidence that certain orally administered nitrates at larger than usual dosage can further increase the tolerance to effort. Amelioration of hypertension or congestive failure may play a significant role in selected patients.", "contents": "Pharmacotherapy of myocardial ischemia. The cornerstones of pharmacotherapy for myocardial ischemia are the nitrites and the beta-adrenergic blocking agents. These drugs not only inhibit cardiac mechanical activity (and therefore energy requirements) in a variety of ways but also redistribute available blood flow to the potentially ischemic segments of cardiac muscle. The least effective dose of nitroglycerin and the most tolerated (or blocking) dose of propranolol provide the optimum in management. There is increasing evidence that certain orally administered nitrates at larger than usual dosage can further increase the tolerance to effort. Amelioration of hypertension or congestive failure may play a significant role in selected patients."}
{"id": "PMID:10491", "title": "Principles in selection of therapy.", "content": "The physician today is presented with a plethora of possibilities in the therapy of each of the aspects of ischemic heart disease (Fig. 15-5). There is the temptation to recommend complex and impossible dietary prescriptions coupled with several pharmaceutical agents for control of anginal pain, hypertension, arrhythmias, hypercholesterolemia, and clinical congestive heart failure. While each of the objectives may be in part valid, the burden on the patient of following such a constraining and difficult life may make it virtually impossible either to enjoy life or to follow the physician's recommendations explicitly. Often a compromise must be reached between theoretically optimal therapy and that which is reasonable and acceptable to the patient. Again, a review of each aspect of the program with the patient may aid in establishing that which is possible rather than that which is ideal.", "contents": "Principles in selection of therapy. The physician today is presented with a plethora of possibilities in the therapy of each of the aspects of ischemic heart disease (Fig. 15-5). There is the temptation to recommend complex and impossible dietary prescriptions coupled with several pharmaceutical agents for control of anginal pain, hypertension, arrhythmias, hypercholesterolemia, and clinical congestive heart failure. While each of the objectives may be in part valid, the burden on the patient of following such a constraining and difficult life may make it virtually impossible either to enjoy life or to follow the physician's recommendations explicitly. Often a compromise must be reached between theoretically optimal therapy and that which is reasonable and acceptable to the patient. Again, a review of each aspect of the program with the patient may aid in establishing that which is possible rather than that which is ideal."}
{"id": "PMID:10504", "title": "Triacetylated insulin: biologic activity and resistance to degradation.", "content": "Tritiated N-hydroxysuccinimide acetate was prepared with specific activities up to 5 Ci/mmole and utilized to prepare tritiated triacetyl insulin. Binding of triacetyl insulin to liver plasma membranes was measured by its capacity to displace 125I-monoiodoinsulin. At low concentrations, less than 10 ng/ml triacetyl insulin appears to be as effective as native insulin in reducing the binding of 125I-monoiodoinsulin to plasma membranes. At concentrations of 20 ng/ml and higher, triacetyl insulin is significantly less effective than native insulin in displacing binding of 125I-monoiodoinsulin to plasma membranes. The properties of triacetyl insulin in this system are not ascribable to deacetylation and conversion of the substituted product to native insulin. Biologic activity of triacetylated insulin was studied in two other in vitro systmes. A comparison was made of the capacity of native beef insulin and its triacetyl derivative to stimulate glucose oxidation by epididymal fat pads. At all three concentrations tested (2, 6, and 18 ng/ml), triacetyl insulin exerted considerable activity, although its potency was significantly less than that of native insulin. Similar effects were observed when biologic activity was measured by induction of tyrosine-alpha-ketoglutarate transaminase in a cultured liver cell system where significant activity of triacetyl insulin was found at concentrations of 10(-9)-10(-7) M. In all systems tested, the activity of triacetylated insulin could not be accounted for by deacetylation and conversion to native insulin. In all systems studied, triacetyl insulin was more resistant to degradation than was monoiodoinsulin.", "contents": "Triacetylated insulin: biologic activity and resistance to degradation. Tritiated N-hydroxysuccinimide acetate was prepared with specific activities up to 5 Ci/mmole and utilized to prepare tritiated triacetyl insulin. Binding of triacetyl insulin to liver plasma membranes was measured by its capacity to displace 125I-monoiodoinsulin. At low concentrations, less than 10 ng/ml triacetyl insulin appears to be as effective as native insulin in reducing the binding of 125I-monoiodoinsulin to plasma membranes. At concentrations of 20 ng/ml and higher, triacetyl insulin is significantly less effective than native insulin in displacing binding of 125I-monoiodoinsulin to plasma membranes. The properties of triacetyl insulin in this system are not ascribable to deacetylation and conversion of the substituted product to native insulin. Biologic activity of triacetylated insulin was studied in two other in vitro systmes. A comparison was made of the capacity of native beef insulin and its triacetyl derivative to stimulate glucose oxidation by epididymal fat pads. At all three concentrations tested (2, 6, and 18 ng/ml), triacetyl insulin exerted considerable activity, although its potency was significantly less than that of native insulin. Similar effects were observed when biologic activity was measured by induction of tyrosine-alpha-ketoglutarate transaminase in a cultured liver cell system where significant activity of triacetyl insulin was found at concentrations of 10(-9)-10(-7) M. In all systems tested, the activity of triacetylated insulin could not be accounted for by deacetylation and conversion to native insulin. In all systems studied, triacetyl insulin was more resistant to degradation than was monoiodoinsulin."}
{"id": "PMID:10505", "title": "Effects of arginine infusion in infants: increased urea synthesis associated with unchanged ammonia blood levels.", "content": "Infusion of L-arginine hydrochloride in infants and children (ages ranging from 1 day to 12 yr) at a dosage of 0.5 g/kg body weight resulted in a dramatic increase in the arginine plasma concentration, with highest values of approximately 7 mmole/liter immediately after the end of the infusion; 120 min later the mean plasma level of the amino acid had decreased to mean values of 1 mmole/liter. These fluctuations were paralleled by increased ornithine concentrations, although the mean plasma levels of this amino acid remained far below those of arginine, i.e., 0.73 and 0.22 mmole/liter after 30 and 90 min, respectively. When expressed on a molar basis, arginine administration resulted in an almost stoichiometric rise in urinary urea excretion. These findings indicate that arginine is rapidly metabolized via urea and ornithine, the latter being transformed to glucose, as evidenced by a significant rise in the blood glucose concentration. Blood gas analyses and serum urea and blood ammonia concentrations determined after the load showed no significant deviations from preinfusion levels. Thus, in contrast to the effects to be expected form studies with tissue culture homogenates, even when administered to newborn infants, arginine does not impair the turnover of the urea cycle.", "contents": "Effects of arginine infusion in infants: increased urea synthesis associated with unchanged ammonia blood levels. Infusion of L-arginine hydrochloride in infants and children (ages ranging from 1 day to 12 yr) at a dosage of 0.5 g/kg body weight resulted in a dramatic increase in the arginine plasma concentration, with highest values of approximately 7 mmole/liter immediately after the end of the infusion; 120 min later the mean plasma level of the amino acid had decreased to mean values of 1 mmole/liter. These fluctuations were paralleled by increased ornithine concentrations, although the mean plasma levels of this amino acid remained far below those of arginine, i.e., 0.73 and 0.22 mmole/liter after 30 and 90 min, respectively. When expressed on a molar basis, arginine administration resulted in an almost stoichiometric rise in urinary urea excretion. These findings indicate that arginine is rapidly metabolized via urea and ornithine, the latter being transformed to glucose, as evidenced by a significant rise in the blood glucose concentration. Blood gas analyses and serum urea and blood ammonia concentrations determined after the load showed no significant deviations from preinfusion levels. Thus, in contrast to the effects to be expected form studies with tissue culture homogenates, even when administered to newborn infants, arginine does not impair the turnover of the urea cycle."}
{"id": "PMID:10506", "title": "Effect of hydrogen ion buffers on photosynthetic oxygen evolution in the blue-green alga, Agmenellum quadruplicatum.", "content": "The photosynthetic oxygen evolution capacity of Agmenelium quadruplication suspended in four hydrogen ion buffers (pH 7.4, 0.05 M) and its synthetic marine growth medium was measured with an oxygen electrode. High rates of oxygen evolution were obtained in the growth medium and N-tris(hydroxymethyl)-methylglycine (Tricine) buffer. Compared to oxygen evolution in the growth medium, rates in phosphate buffer and N-tris(hydroxymethyl)-2-aminoethanesulphonic acid (TES) buffer were sometimes reduced by up to 30% and rates in tris (hydroxymethyl) amino-methane (Tris) were consistently reduced by 50%. An incubation-rinsing procedure caused inhibition of oxygen evolution in TES, phosphate, and Tris by 50 to 100%. Oxygen evolution could be restored to cells rinsed in TES or phosphate by resuspension in growth medium or in buffer plus magnesium and calcium ions. Bezoquinone-supported oxygen evolution was not affected by rinsing with any buffer tested except Tris. Ferricyanide was photoreduced at a low rate by cells rinsed in Tes but at a high rate in TES plus magnesium and calcium ions. We interpreted our results to mean that, in Agmenellum quadruplicatum, inhibition of photosynthetic oxygen evolution by Tris occurs at the level of photosystem 2 while the effects of TES and phosphate are on electron-transport occurring after the rate-limiting reaction.", "contents": "Effect of hydrogen ion buffers on photosynthetic oxygen evolution in the blue-green alga, Agmenellum quadruplicatum. The photosynthetic oxygen evolution capacity of Agmenelium quadruplication suspended in four hydrogen ion buffers (pH 7.4, 0.05 M) and its synthetic marine growth medium was measured with an oxygen electrode. High rates of oxygen evolution were obtained in the growth medium and N-tris(hydroxymethyl)-methylglycine (Tricine) buffer. Compared to oxygen evolution in the growth medium, rates in phosphate buffer and N-tris(hydroxymethyl)-2-aminoethanesulphonic acid (TES) buffer were sometimes reduced by up to 30% and rates in tris (hydroxymethyl) amino-methane (Tris) were consistently reduced by 50%. An incubation-rinsing procedure caused inhibition of oxygen evolution in TES, phosphate, and Tris by 50 to 100%. Oxygen evolution could be restored to cells rinsed in TES or phosphate by resuspension in growth medium or in buffer plus magnesium and calcium ions. Bezoquinone-supported oxygen evolution was not affected by rinsing with any buffer tested except Tris. Ferricyanide was photoreduced at a low rate by cells rinsed in Tes but at a high rate in TES plus magnesium and calcium ions. We interpreted our results to mean that, in Agmenellum quadruplicatum, inhibition of photosynthetic oxygen evolution by Tris occurs at the level of photosystem 2 while the effects of TES and phosphate are on electron-transport occurring after the rate-limiting reaction."}
{"id": "PMID:10508", "title": "A new form of antihistamine--the H2-receptor antagonist.", "content": "A new group of drugs, the histamine2 (H2)-receptor antagonists, act on receptors in the stomach to reduce acid secretion when this is stimulated by histamine, pentagastrin, the vagus nerve or food. The reduction in acid secretion is profound and may approach the degree of reduction brought about by gastric surgery. The H2-receptor antagonist metiamide, administered orally, has been used successfully in the treatment of duodenal ulcer and the Zollinger-Ellison syndrome, but it has been shown to cause agranulocytosis. Trials are in process with an analogue, cimetidine (Tagamet, SKF), which has a different chemical structure from metiamide and has not caused haematological changes in animals or man. These drugs offer the prospect of successful medical management of duodenal ulcer, while a study of their effects on H2-receptors elsewhere in the body may reveal other therapeutic benefits.", "contents": "A new form of antihistamine--the H2-receptor antagonist. A new group of drugs, the histamine2 (H2)-receptor antagonists, act on receptors in the stomach to reduce acid secretion when this is stimulated by histamine, pentagastrin, the vagus nerve or food. The reduction in acid secretion is profound and may approach the degree of reduction brought about by gastric surgery. The H2-receptor antagonist metiamide, administered orally, has been used successfully in the treatment of duodenal ulcer and the Zollinger-Ellison syndrome, but it has been shown to cause agranulocytosis. Trials are in process with an analogue, cimetidine (Tagamet, SKF), which has a different chemical structure from metiamide and has not caused haematological changes in animals or man. These drugs offer the prospect of successful medical management of duodenal ulcer, while a study of their effects on H2-receptors elsewhere in the body may reveal other therapeutic benefits."}
{"id": "PMID:10509", "title": "Streptococcal sore throat in general practice--a controlled study.", "content": "A controlled study was undertaken to determine the incidence of Group A haemolytic streptococci and other bacterial pathogens in throat swabs from patients presenting with sore throats. The isolation rate (38-8%) of Group A haemolytic streptococci from patients with acute tonsillitis was significantly higher than the isolation rate (8-9%) in a control group, but there was no significant difference in the isolation rates in patients diagnosed as having acute pharyngitis compared with the control group. There was no difference in the isolation rates of the other bacterial pathogens in the patient and control groups. In-vitro antibiotic studies were performed, and a comparison was made of the results of these tests and the treatment prescribed.", "contents": "Streptococcal sore throat in general practice--a controlled study. A controlled study was undertaken to determine the incidence of Group A haemolytic streptococci and other bacterial pathogens in throat swabs from patients presenting with sore throats. The isolation rate (38-8%) of Group A haemolytic streptococci from patients with acute tonsillitis was significantly higher than the isolation rate (8-9%) in a control group, but there was no significant difference in the isolation rates in patients diagnosed as having acute pharyngitis compared with the control group. There was no difference in the isolation rates of the other bacterial pathogens in the patient and control groups. In-vitro antibiotic studies were performed, and a comparison was made of the results of these tests and the treatment prescribed."}
{"id": "PMID:10527", "title": "Reflex increase in coronary vascular resistance in patients with ischemic heart disease.", "content": "To assess possible coronary vasoconstriction in patients with ischemic heart disease, we measured coronary vascular resistance in 12 patients with normal hearts and 12 with coronary disease before and during the initial 50 seconds of cold pressor test, a stimulus known to produce systemic vasoconstriction. Control coronary vascular resistance was similar in the two groups, and although it did not change in patients with normal vessels, it rose by 27 per cent (P less than 0.005) in the group with coronary disease during the cold pressor test. In three of 12 patients with coronary disease coronary flow actually declined despite an increase in arterial pressure; in four, angina was precipitated. Phentolamine abolished increases in arterial pressure and coronary vascular resistance during the test in three patients with coronary disease. Adrenergically mediated coronary vascular tone may be an important determinant of coronary blood flow and may contribute to ischemia in patients with coronary disease.", "contents": "Reflex increase in coronary vascular resistance in patients with ischemic heart disease. To assess possible coronary vasoconstriction in patients with ischemic heart disease, we measured coronary vascular resistance in 12 patients with normal hearts and 12 with coronary disease before and during the initial 50 seconds of cold pressor test, a stimulus known to produce systemic vasoconstriction. Control coronary vascular resistance was similar in the two groups, and although it did not change in patients with normal vessels, it rose by 27 per cent (P less than 0.005) in the group with coronary disease during the cold pressor test. In three of 12 patients with coronary disease coronary flow actually declined despite an increase in arterial pressure; in four, angina was precipitated. Phentolamine abolished increases in arterial pressure and coronary vascular resistance during the test in three patients with coronary disease. Adrenergically mediated coronary vascular tone may be an important determinant of coronary blood flow and may contribute to ischemia in patients with coronary disease."}
{"id": "PMID:10531", "title": "Proteolytic activity in liver cells from mouse, rat, Ehrlich ascites carcinoma bearing mouse and in Ehrlich ascites carcinoma cells.", "content": "The activity of intracellular proteinases from Ehrlich ascites carcinoma bearing mice were compared with that from liver cells of normal mice and rats. The activity of intracellular proteinases was measured in the supernatant of Ehrlich ascites carcinoma cells homogenate. The activity of intracellular proteinases in normal mouse and normal rat liver were different at pH 3.5, pH 6.0 and pH 7.5. The activity in liver cells from Ehlrich ascites carcinoma bearing mouse at pH 3.5 was not significantly changed from normal mouse or rat liver cells, however at pH 6.0 and pH 7.5 the activity in the affected liver significantly decreased. The proteolytic activity in the supernatant of Ehrlich ascites tumor cell homogenate was 0.110 E750 mmu/mgN at pH 7.5, 0.154 E750 mmu/mgN at pH 3.5. The proteolytic activity at pH 6.0 was not detected in any experiment.", "contents": "Proteolytic activity in liver cells from mouse, rat, Ehrlich ascites carcinoma bearing mouse and in Ehrlich ascites carcinoma cells. The activity of intracellular proteinases from Ehrlich ascites carcinoma bearing mice were compared with that from liver cells of normal mice and rats. The activity of intracellular proteinases was measured in the supernatant of Ehrlich ascites carcinoma cells homogenate. The activity of intracellular proteinases in normal mouse and normal rat liver were different at pH 3.5, pH 6.0 and pH 7.5. The activity in liver cells from Ehlrich ascites carcinoma bearing mouse at pH 3.5 was not significantly changed from normal mouse or rat liver cells, however at pH 6.0 and pH 7.5 the activity in the affected liver significantly decreased. The proteolytic activity in the supernatant of Ehrlich ascites tumor cell homogenate was 0.110 E750 mmu/mgN at pH 7.5, 0.154 E750 mmu/mgN at pH 3.5. The proteolytic activity at pH 6.0 was not detected in any experiment."}
{"id": "PMID:10538", "title": "Correlation of the oxytocin challenge test with perinatal outcome.", "content": "A total of 234 oxytocin challenge tests (OCT) were performed on 100 high-risk patients. The results were negative (N) in 68 of these 100 patients, suspicious (S) in 22, and positive (P) in 10. The incidence of late decelerations during labor was N, 5%; S, 40%; P, 86%; and meconium staining of the amniotic fluid was N, 4%; S, 5%; and P, 30%. The cesarean section rate was N, 16%; S, 36%; and P, 60%; and of these the cesarean section rate for fetal indications was N, 9%; S, 25%; and P, 67%. The overall perinatal mortality in the study group was 2% (N, 1.5%; S, 0%; P, 10%). The results confirm the negative OCT as innocuous and positive OCT as the most ominous. They also indicate that the majority of patients with positive OCT can be delivered vaginally without endangering the fetus if fetal scalp blood pH determinations can be performed.", "contents": "Correlation of the oxytocin challenge test with perinatal outcome. A total of 234 oxytocin challenge tests (OCT) were performed on 100 high-risk patients. The results were negative (N) in 68 of these 100 patients, suspicious (S) in 22, and positive (P) in 10. The incidence of late decelerations during labor was N, 5%; S, 40%; P, 86%; and meconium staining of the amniotic fluid was N, 4%; S, 5%; and P, 30%. The cesarean section rate was N, 16%; S, 36%; and P, 60%; and of these the cesarean section rate for fetal indications was N, 9%; S, 25%; and P, 67%. The overall perinatal mortality in the study group was 2% (N, 1.5%; S, 0%; P, 10%). The results confirm the negative OCT as innocuous and positive OCT as the most ominous. They also indicate that the majority of patients with positive OCT can be delivered vaginally without endangering the fetus if fetal scalp blood pH determinations can be performed."}
{"id": "PMID:10539", "title": "Microstructure of the solder-casting zone in bridges of dental gold alloys.", "content": "The composition and structure were studied in the cast and in the solder of bridges which had failed clinically. Both materials were gold alloys but with different contents of Pt, Ag and Zn. The metallographic investigation revealed defects mostly in the solder, situated in the subsurface layer. SEM studied of the fracture surface revealed large porosites and a structure of dense parallel lines--striations--, indicating that the material had failed from fatigue. The materials in the fractured bridges were identified by micro-probe measurements. It was stated that cast material and solder material used together, were of different composition.", "contents": "Microstructure of the solder-casting zone in bridges of dental gold alloys. The composition and structure were studied in the cast and in the solder of bridges which had failed clinically. Both materials were gold alloys but with different contents of Pt, Ag and Zn. The metallographic investigation revealed defects mostly in the solder, situated in the subsurface layer. SEM studied of the fracture surface revealed large porosites and a structure of dense parallel lines--striations--, indicating that the material had failed from fatigue. The materials in the fractured bridges were identified by micro-probe measurements. It was stated that cast material and solder material used together, were of different composition."}
{"id": "PMID:10541", "title": "Gingival crevicular fluid: a new diagnostic aid in managing the periodontal patient.", "content": "On the whole, the studies on GCF have demonstrated that the flow of this fluid is sufficiently indicative of the inflammatory state that it can be used under a variety of clinical conditions to monitor and control gingival inflammation. Since gingivitis is extremely common, and since some cases of gingivitis presumably do not progress to periodontitis, the question could be posed whether or not a concerted effort to control inflammation (i.e. trying to achieve a GCF flow as near to zero as possible) would be clinically significant. Until there is evidence to the contrary, the answer must be \"yes\", since few cases are known where periodontitis occurs without being preceded by gingivitis. In other words, the control of all gingivitis, if feasible, should prevent most cases of periodontitis. Although control of all gingivitis would mean the treatment of many cases that would not progress to periodontal breakdown, such efforts would be worth-while if most periodontal destruction were prevented. Even the early destructive lesion exhibiting little or no inflammation may soon be identified, mainly because the minute volume of fluid collected from the gingival crevice can now be measured accurately. Accordingly, the concentration of various constituents in the GCF can be determined, which should lead to the development of tests to differentiate between pockets undergoing active destruction with minimal inflammation from the majority of active lesions that are intimately involved with frank inflammation. Thus, a clinician would measure sub-clinical gingival inflammation by measuring GCF flow, then differentiate destructive from quiescent lesions by analyzing the GCF sample for some constituent(s), chemical or microbial (Listgarten et al. 1975) indicative of the periodontal destructive process. Monitoring the flow of GCF might be of value in other clinical situations. For example, one could monitor the response of gingival tissues to various restorative and prosthetic procedures (Strauss et al. 1975) to ensure that these procedures do not aggravate the periodontal tissues and induce gingivitis or periodontitis. The education of the patient should be easier since patients can read their own numbers on the GCF meter at each examination and self-evaluate their personal periodontal condition and the effectiveness of their home care. Even the education of the dental student should be easier since he or she would have the means of self-evaluating the effectiveness of treatment, and not be as dependent upon the subjective assessment of his efforts by an instructor. Finally, monitoring GCF for various components could provide the dentist with a valuable means of easily screening patients for systemic disease. Obviously, this area of investigation is in its infancy, but does promise an exciting future for the oral diagnostician.", "contents": "Gingival crevicular fluid: a new diagnostic aid in managing the periodontal patient. On the whole, the studies on GCF have demonstrated that the flow of this fluid is sufficiently indicative of the inflammatory state that it can be used under a variety of clinical conditions to monitor and control gingival inflammation. Since gingivitis is extremely common, and since some cases of gingivitis presumably do not progress to periodontitis, the question could be posed whether or not a concerted effort to control inflammation (i.e. trying to achieve a GCF flow as near to zero as possible) would be clinically significant. Until there is evidence to the contrary, the answer must be \"yes\", since few cases are known where periodontitis occurs without being preceded by gingivitis. In other words, the control of all gingivitis, if feasible, should prevent most cases of periodontitis. Although control of all gingivitis would mean the treatment of many cases that would not progress to periodontal breakdown, such efforts would be worth-while if most periodontal destruction were prevented. Even the early destructive lesion exhibiting little or no inflammation may soon be identified, mainly because the minute volume of fluid collected from the gingival crevice can now be measured accurately. Accordingly, the concentration of various constituents in the GCF can be determined, which should lead to the development of tests to differentiate between pockets undergoing active destruction with minimal inflammation from the majority of active lesions that are intimately involved with frank inflammation. Thus, a clinician would measure sub-clinical gingival inflammation by measuring GCF flow, then differentiate destructive from quiescent lesions by analyzing the GCF sample for some constituent(s), chemical or microbial (Listgarten et al. 1975) indicative of the periodontal destructive process. Monitoring the flow of GCF might be of value in other clinical situations. For example, one could monitor the response of gingival tissues to various restorative and prosthetic procedures (Strauss et al. 1975) to ensure that these procedures do not aggravate the periodontal tissues and induce gingivitis or periodontitis. The education of the patient should be easier since patients can read their own numbers on the GCF meter at each examination and self-evaluate their personal periodontal condition and the effectiveness of their home care. Even the education of the dental student should be easier since he or she would have the means of self-evaluating the effectiveness of treatment, and not be as dependent upon the subjective assessment of his efforts by an instructor. Finally, monitoring GCF for various components could provide the dentist with a valuable means of easily screening patients for systemic disease. Obviously, this area of investigation is in its infancy, but does promise an exciting future for the oral diagnostician."}
{"id": "PMID:10544", "title": "[Neuroaminergic control of anterior pituitary secretions (author's transl)].", "content": "The demonstration and identification of monoamines and of aminergic tracts in the central nervous system has permitted a study of their role in the control of the liberation of hypothalamic releasing hormones. Knowledge of the role of these hypothalamic neurohormones in the release of pituitary hormones is at present under study. The role of monoamines in the control of pituitary hormone functions depends narrowly on pharmacological methods intervening either in the synthesis of neuroamines or in their action on a specific receptor. The authors consider successively the implication of monoamines in the control of liberation of ACTH, GH, TSH, prolactin and gonadotropic hormones. The role of aminergic mechanisms in the physiology of pituitary releasing hormones forms an integral part of homeostasis. Knowledge of these mechanisms leads to a clinical study of their role in disorders of hypothalamo-pituitary function.", "contents": "[Neuroaminergic control of anterior pituitary secretions (author's transl)]. The demonstration and identification of monoamines and of aminergic tracts in the central nervous system has permitted a study of their role in the control of the liberation of hypothalamic releasing hormones. Knowledge of the role of these hypothalamic neurohormones in the release of pituitary hormones is at present under study. The role of monoamines in the control of pituitary hormone functions depends narrowly on pharmacological methods intervening either in the synthesis of neuroamines or in their action on a specific receptor. The authors consider successively the implication of monoamines in the control of liberation of ACTH, GH, TSH, prolactin and gonadotropic hormones. The role of aminergic mechanisms in the physiology of pituitary releasing hormones forms an integral part of homeostasis. Knowledge of these mechanisms leads to a clinical study of their role in disorders of hypothalamo-pituitary function."}
{"id": "PMID:10545", "title": "Diagnosis and treatment of duodenal ulcer in infancy and childhood.", "content": "An awareness of the modes of presentation in childhood duodenal ulcer disease is necessary for prompt diagnosis and treatment. Therapy should be based on the rationale of decreasing acid secretion and providing adequate buffering of gastric acid throughout the day. Because of the high incidence of recurrence in children, aggressive diagnosis and treatment of duodenal ulcer are indicated in any child suspected of having the disease.", "contents": "Diagnosis and treatment of duodenal ulcer in infancy and childhood. An awareness of the modes of presentation in childhood duodenal ulcer disease is necessary for prompt diagnosis and treatment. Therapy should be based on the rationale of decreasing acid secretion and providing adequate buffering of gastric acid throughout the day. Because of the high incidence of recurrence in children, aggressive diagnosis and treatment of duodenal ulcer are indicated in any child suspected of having the disease."}
{"id": "PMID:10546", "title": "Genetic variation of lysosomal acid lipase.", "content": "Lysosomal acid lipase (LAL) activity was measured using a new fluorometric assay in cultured skin fibroblasts from eight control subjects, two obligate heterozygotes for Wolman's disease (WD), one patient with WD, and one patient with cholesteryl ester storage disease (CESD). The LAL activities (mean+/-SD) were 25.8+/-8.2, 13.2+/-0.1,1.1, and 1.4 nmol 4-methylumbelliferyl oleate (4-MUO) hydrolyzed/min/mg protein, respectively. These results compare favorably with those obtained using standard radioassays. The LAL activities of two cultures of amniotic fluid cells were 12.1 and 10.5. The LAL activity (mean+/-SD) of peripheral leukocytes obtained from 34 laboratory volunteers (19 females, 15 males) was 4.0+/-1.8. Partially purified lymphocytes contained about 25 times as much LAL activity as did granulocytes. Cellogel electrophoresis, followed by staining with 4-MUO, showed at least two bands of LAL (A and B) from normal fibroblasts, amniotic fluid cells, and lymphocytes. Band A was absent from WD and CESD fibroblasts and was reduced in fibroblasts of the WD heterozygotes.", "contents": "Genetic variation of lysosomal acid lipase. Lysosomal acid lipase (LAL) activity was measured using a new fluorometric assay in cultured skin fibroblasts from eight control subjects, two obligate heterozygotes for Wolman's disease (WD), one patient with WD, and one patient with cholesteryl ester storage disease (CESD). The LAL activities (mean+/-SD) were 25.8+/-8.2, 13.2+/-0.1,1.1, and 1.4 nmol 4-methylumbelliferyl oleate (4-MUO) hydrolyzed/min/mg protein, respectively. These results compare favorably with those obtained using standard radioassays. The LAL activities of two cultures of amniotic fluid cells were 12.1 and 10.5. The LAL activity (mean+/-SD) of peripheral leukocytes obtained from 34 laboratory volunteers (19 females, 15 males) was 4.0+/-1.8. Partially purified lymphocytes contained about 25 times as much LAL activity as did granulocytes. Cellogel electrophoresis, followed by staining with 4-MUO, showed at least two bands of LAL (A and B) from normal fibroblasts, amniotic fluid cells, and lymphocytes. Band A was absent from WD and CESD fibroblasts and was reduced in fibroblasts of the WD heterozygotes."}
{"id": "PMID:10549", "title": "Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium.", "content": "In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. 1. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a \"Wenckebach-like\" phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50-60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. 4. At pH 5.5 excess Ca (4 mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this beta-stimulating compound remained unchanged.", "contents": "Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium. In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. 1. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a \"Wenckebach-like\" phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50-60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. 4. At pH 5.5 excess Ca (4 mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this beta-stimulating compound remained unchanged."}
{"id": "PMID:10550", "title": "[Acute kidney failure during periarteritis nodosa].", "content": "In 9 patients aged 16 to 71 years with acute renal failure, histological examination disclosed polyarteritis nodosa. Symptoms of rapidly progressive glomerulonephritis (GN) were present in 7 cases. Hypertension was a constant feature. Fever and muscular articular and cutaneous signs occured at times simulating Henoch-Sch\u00f6nlein purpura. Necrotizing angiitis was a constant finding, with perivascular granuloma in 7 cases. Lesions affecting smaller arteries were associated with diffuse or segmental extracapillary GN, and lesions of larger arteries with ischaemic appearance of the glomeruli. Diagnosis was obtained during life by percutaneous renal biopsy in 5 patients and muscular or cutaneous biopsy in 2 other patients, whereas the evidence was only obtained on post mortem examination in the 2 remaining patients. In the 6 renal biopsies examined by immunofluorescence, fibrinogen was always present in glomeruli and/or arteries. In one patient there was a linear deposit of IgG along glomerular basement membrane (GBM) and there were circulating antibodies directed against GBM. Arteries of different sizes may be damaged in various organs, as showed by arteriography and autopsy. Steroid therapy and immunosuppressive drugs had no effect on renal symptoms. 8 out of 9 patients died rapidly, in 6 the death was due to extrarenal localization of the disease, even though uraemia was controlled by haemodialysis. The last patient died 2 years after onset of the disease, while being on maintenance haemodialysis treatment.", "contents": "[Acute kidney failure during periarteritis nodosa]. In 9 patients aged 16 to 71 years with acute renal failure, histological examination disclosed polyarteritis nodosa. Symptoms of rapidly progressive glomerulonephritis (GN) were present in 7 cases. Hypertension was a constant feature. Fever and muscular articular and cutaneous signs occured at times simulating Henoch-Sch\u00f6nlein purpura. Necrotizing angiitis was a constant finding, with perivascular granuloma in 7 cases. Lesions affecting smaller arteries were associated with diffuse or segmental extracapillary GN, and lesions of larger arteries with ischaemic appearance of the glomeruli. Diagnosis was obtained during life by percutaneous renal biopsy in 5 patients and muscular or cutaneous biopsy in 2 other patients, whereas the evidence was only obtained on post mortem examination in the 2 remaining patients. In the 6 renal biopsies examined by immunofluorescence, fibrinogen was always present in glomeruli and/or arteries. In one patient there was a linear deposit of IgG along glomerular basement membrane (GBM) and there were circulating antibodies directed against GBM. Arteries of different sizes may be damaged in various organs, as showed by arteriography and autopsy. Steroid therapy and immunosuppressive drugs had no effect on renal symptoms. 8 out of 9 patients died rapidly, in 6 the death was due to extrarenal localization of the disease, even though uraemia was controlled by haemodialysis. The last patient died 2 years after onset of the disease, while being on maintenance haemodialysis treatment."}
{"id": "PMID:10562", "title": "Treatment of angina pectoris. Pharmacologic approaches.", "content": "The short-acting nitrite sublingual nitroglycerin is the cornerstone of drug treatment of angina pectoris. It is most useful when given two to three minutes before activity that may precipitate an anginal attack. If disabling angina persists despite medical management and there is no contraindication, the beta-adrenergic blocking agent propranolol should be tried before coronary artery surgery is considered. Newer bera-adrenergic blocking agents do not appear to be more effective than propranolol. Digitalis may be beneficial in patients with congestive heart failure or with cardiac arrhythmias responsive to digitalis and in some patients with radiographic evidence of left ventricular enlargement or with nocturnal angina resulting from increased left ventricular end-diastolic volume. If bypass graft surgery is done, medical management must be continued postoperatively.", "contents": "Treatment of angina pectoris. Pharmacologic approaches. The short-acting nitrite sublingual nitroglycerin is the cornerstone of drug treatment of angina pectoris. It is most useful when given two to three minutes before activity that may precipitate an anginal attack. If disabling angina persists despite medical management and there is no contraindication, the beta-adrenergic blocking agent propranolol should be tried before coronary artery surgery is considered. Newer bera-adrenergic blocking agents do not appear to be more effective than propranolol. Digitalis may be beneficial in patients with congestive heart failure or with cardiac arrhythmias responsive to digitalis and in some patients with radiographic evidence of left ventricular enlargement or with nocturnal angina resulting from increased left ventricular end-diastolic volume. If bypass graft surgery is done, medical management must be continued postoperatively."}
{"id": "PMID:10564", "title": "An eighteen months' study of the clinical response to metoprolol, a selective beta1-receptor blocking agent, in patients with angina pectoris.", "content": "Following an initial dose response study, metoprolol, a selective beta1-receptor blocking agent, was compared with equipotent dosages of propanolol in a double blind cross-over study, including exercise tolerance tests, on fourteen patients with angina pectoris. Long term therapy with metoprolol then followed until the seventy-second week. Patients performed 8% more total work on metoprolol with 15% more work recorded up to the onset of S-T depression, in comparison with propranolol. In the long term, ther was no significant difference in work performed when the daily dosage of metoprolol was changed from a q.i.d. to a b.d. regime. Metoprolol was shown to be an effective anti-anginal compound with good tolerance and safety, with gradual improvement in underlying myocardial ischaemia during long term treatment.", "contents": "An eighteen months' study of the clinical response to metoprolol, a selective beta1-receptor blocking agent, in patients with angina pectoris. Following an initial dose response study, metoprolol, a selective beta1-receptor blocking agent, was compared with equipotent dosages of propanolol in a double blind cross-over study, including exercise tolerance tests, on fourteen patients with angina pectoris. Long term therapy with metoprolol then followed until the seventy-second week. Patients performed 8% more total work on metoprolol with 15% more work recorded up to the onset of S-T depression, in comparison with propranolol. In the long term, ther was no significant difference in work performed when the daily dosage of metoprolol was changed from a q.i.d. to a b.d. regime. Metoprolol was shown to be an effective anti-anginal compound with good tolerance and safety, with gradual improvement in underlying myocardial ischaemia during long term treatment."}
{"id": "PMID:10560", "title": "Piperazine derivatives of dimethylxanthines. IV. Reaction of beta,gamma-epoxypropyldimethylxanthines with piperazines.", "content": "In the reaction of 7-resp. 1-beta,gamma-epoxyproplderivatives of theophylline (Th) or theobromine (Tb) with piperazine and N-monoalkyl or monoarylpiperazines the corresponding 7-resp. 1-beta-hydroxy-gamma-piperazinopropyl-Th (1-8) resp. Tb (9-16) were formed. In preliminary screening some of the new compounds showed strong antagonism with histamine H1 receptor and with endogenous histamine.", "contents": "Piperazine derivatives of dimethylxanthines. IV. Reaction of beta,gamma-epoxypropyldimethylxanthines with piperazines. In the reaction of 7-resp. 1-beta,gamma-epoxyproplderivatives of theophylline (Th) or theobromine (Tb) with piperazine and N-monoalkyl or monoarylpiperazines the corresponding 7-resp. 1-beta-hydroxy-gamma-piperazinopropyl-Th (1-8) resp. Tb (9-16) were formed. In preliminary screening some of the new compounds showed strong antagonism with histamine H1 receptor and with endogenous histamine."}
{"id": "PMID:10565", "title": "Pneumococcal antigen in pneumonia. A post-mortem study with the histological and bacteriological findings.", "content": "Pneumococcal capsular antigens can be detected in lung tissue by counter-current immunoelectrophoresis even when, following antibiotics, post-mortem bacterilogy suggests that Escherichia coli has replaced pneumococci. The results suggest that antipneumococcal therapy would benefit at least 55% of patients critically ill with lung infection and that the potentially toxic drugs directed at coliform bacteria may be unnecessary.", "contents": "Pneumococcal antigen in pneumonia. A post-mortem study with the histological and bacteriological findings. Pneumococcal capsular antigens can be detected in lung tissue by counter-current immunoelectrophoresis even when, following antibiotics, post-mortem bacterilogy suggests that Escherichia coli has replaced pneumococci. The results suggest that antipneumococcal therapy would benefit at least 55% of patients critically ill with lung infection and that the potentially toxic drugs directed at coliform bacteria may be unnecessary."}
{"id": "PMID:10561", "title": "The stability of N-pyrrolidinomethyltetracycline in solutions.", "content": "In aqueous solution N-pyrrolidinomethyltetracycline (PTC) undergoes decomposition into tetracycline, epitetracylcine, anhydroepitetracycline and ynhydrotetracycline. The decomposition products were identified and separated  by TLC and their activity was estimated microbiologically.", "contents": "The stability of N-pyrrolidinomethyltetracycline in solutions. In aqueous solution N-pyrrolidinomethyltetracycline (PTC) undergoes decomposition into tetracycline, epitetracylcine, anhydroepitetracycline and ynhydrotetracycline. The decomposition products were identified and separated  by TLC and their activity was estimated microbiologically."}
{"id": "PMID:10570", "title": "Catecholamine-stimulated cyclic GMP accumulation in the rat pineal: apparent presynaptic site of action.", "content": "Guanosine 3':5'-cyclic monophosphate (cGMP) increased 7-fold in rat pineal glands incubated in the presence of l-norepinephrine. This response consisted of two components-one was stereospecific and inhibited by alpha-adrenergic antagonists while the other was not stereospecific and not readily inhibited by antagonists. Although l-isoproterenol was more potent than l-norepinephrine it had less intrinsic activity and its action was not stereospecifc. The increase in cGMP caused by these catecholamines, unlike that of adenosine 3':5'-cyclic monophosphate (cAMP), was dependent upon extracellular calcium. Ouabain and high levels of potassium produced a marked, calcium-dependent increase in pineal cGMP, without affecting cAMP. There was no effect of cholinergic agonists on cGMP. Surgical denervation markedly reduced the cGMP response to stimulation by l-norepinephrine, potassium, or ouabain. This was in contrast to the enhanced response of cAMP in denervated glands. The nonspecific increase in cGMP caused by l-isoproterenol, however, was not affected by denervation. These data demonstrate the existence of a calcium-dependent presynaptic mechanism for the generation of cGMP which may be mediated by an alpha-adrenergic-like receptor. In addition, the mechanisms regulating pineal cGMP appear to be physiologically distinct from those regulating cAMP.", "contents": "Catecholamine-stimulated cyclic GMP accumulation in the rat pineal: apparent presynaptic site of action. Guanosine 3':5'-cyclic monophosphate (cGMP) increased 7-fold in rat pineal glands incubated in the presence of l-norepinephrine. This response consisted of two components-one was stereospecific and inhibited by alpha-adrenergic antagonists while the other was not stereospecific and not readily inhibited by antagonists. Although l-isoproterenol was more potent than l-norepinephrine it had less intrinsic activity and its action was not stereospecifc. The increase in cGMP caused by these catecholamines, unlike that of adenosine 3':5'-cyclic monophosphate (cAMP), was dependent upon extracellular calcium. Ouabain and high levels of potassium produced a marked, calcium-dependent increase in pineal cGMP, without affecting cAMP. There was no effect of cholinergic agonists on cGMP. Surgical denervation markedly reduced the cGMP response to stimulation by l-norepinephrine, potassium, or ouabain. This was in contrast to the enhanced response of cAMP in denervated glands. The nonspecific increase in cGMP caused by l-isoproterenol, however, was not affected by denervation. These data demonstrate the existence of a calcium-dependent presynaptic mechanism for the generation of cGMP which may be mediated by an alpha-adrenergic-like receptor. In addition, the mechanisms regulating pineal cGMP appear to be physiologically distinct from those regulating cAMP."}
{"id": "PMID:10571", "title": "Erythrocyte membranes undergo cooperative, pH-sensitive state transitions in the physiological temperature range: evidence from Raman spectroscopy.", "content": "We have examined the Raman scattering from erythrocyte ghosts at 2700 to 3000 cm-1 (CH-stretching region). Plots of the intensity (I) of the 2930 cm-1 band relative to the intensity of the thermally stable 2850 cm-1 band, i.e., the [I2930/I2850] ratio, as a function of temperature reveal a sharp discontinuity, which at pH 7.4 has a lower limit of 38 degrees and is irreversible above 42 degrees. [I2930/I2850] is stable between pH 7.0 and pH 7.4, but increases or decreases sharply below pH 7.0 or above pH 7.5, respectively. Reduction of pH to 6.5 lowers the transition temperature by about 16 degrees, and a shift to pH 6.0 drops the transition range to 0 to 7 degrees. The above effects of temperature and pH on Raman scattering closely correspond to those detected by studies on the interaction of membrane protein fluorophores and lipid-soluble fluorescence quenchers [Bieri, V. and Wallach, D.F.H. (1975) Biochim. Biophys. Acta 406, 415-423]. Taken together, these results suggest that the transitions represent concerted process, involving hydrophobic amino acid residues and lipid chains at apolar protein-lipid boundaries.", "contents": "Erythrocyte membranes undergo cooperative, pH-sensitive state transitions in the physiological temperature range: evidence from Raman spectroscopy. We have examined the Raman scattering from erythrocyte ghosts at 2700 to 3000 cm-1 (CH-stretching region). Plots of the intensity (I) of the 2930 cm-1 band relative to the intensity of the thermally stable 2850 cm-1 band, i.e., the [I2930/I2850] ratio, as a function of temperature reveal a sharp discontinuity, which at pH 7.4 has a lower limit of 38 degrees and is irreversible above 42 degrees. [I2930/I2850] is stable between pH 7.0 and pH 7.4, but increases or decreases sharply below pH 7.0 or above pH 7.5, respectively. Reduction of pH to 6.5 lowers the transition temperature by about 16 degrees, and a shift to pH 6.0 drops the transition range to 0 to 7 degrees. The above effects of temperature and pH on Raman scattering closely correspond to those detected by studies on the interaction of membrane protein fluorophores and lipid-soluble fluorescence quenchers [Bieri, V. and Wallach, D.F.H. (1975) Biochim. Biophys. Acta 406, 415-423]. Taken together, these results suggest that the transitions represent concerted process, involving hydrophobic amino acid residues and lipid chains at apolar protein-lipid boundaries."}
{"id": "PMID:10572", "title": "Central regulation of sympathetic neuron development.", "content": "The sixth lumbar (L-6) ganglion has been used to study the central regulation of peripheral sympathetic neuron development. During post-natal ontogeny, tyrosine hydroxylase [tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity increased 60-fold, while total protein rose 10-fold in the ganglion. Transection of the spinal cord at the fifth thoracic (T-5) segment in neonatal rats prevented the normal developmental increase in tyrosine hydroxylase activity of the L-6 ganglion. However, spinal transection did not alter the ontogeny of tyrosine hydroxylase in the superior cervical ganglion, which derives its innervation from spinal segments rostral to the surgical lesion. Thus, spinal transection interfered with the maturation of sympathetic neurons distal to, but not proximal to, the lesion. The effect of transection on the L-6 ganglion persisted for at least one month, the longest time tested. Our observations suggest that trans-synaptic regulation of adrenergic maturation in the periphery is governed by suprasegmental mechanisms in the central nervous system.", "contents": "Central regulation of sympathetic neuron development. The sixth lumbar (L-6) ganglion has been used to study the central regulation of peripheral sympathetic neuron development. During post-natal ontogeny, tyrosine hydroxylase [tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity increased 60-fold, while total protein rose 10-fold in the ganglion. Transection of the spinal cord at the fifth thoracic (T-5) segment in neonatal rats prevented the normal developmental increase in tyrosine hydroxylase activity of the L-6 ganglion. However, spinal transection did not alter the ontogeny of tyrosine hydroxylase in the superior cervical ganglion, which derives its innervation from spinal segments rostral to the surgical lesion. Thus, spinal transection interfered with the maturation of sympathetic neurons distal to, but not proximal to, the lesion. The effect of transection on the L-6 ganglion persisted for at least one month, the longest time tested. Our observations suggest that trans-synaptic regulation of adrenergic maturation in the periphery is governed by suprasegmental mechanisms in the central nervous system."}
{"id": "PMID:10569", "title": "[Purification and properties of L-glutamine and L-asparagine deaminase from Pseudomonas aurantiaca IBPM-14].", "content": "An enzymic preparation of L-glutamine and L-asparagine deamidase was obtained from Pseudomonas auractiaca IBPM B-14. The preparation was purified 100--150-fold by thermal treatment and chromotography on columns with biogel P-150 and DEAE-cellulose. The enzymic activity was measured by the methods of hydroxylaminolysis and direct nesslerization. The deamidase preparation had an activity of 51 i. u. by glutamine and 15 i. e. by asparagine. Evidence on the pH effect on the deamidase activity was accumulated.", "contents": "[Purification and properties of L-glutamine and L-asparagine deaminase from Pseudomonas aurantiaca IBPM-14]. An enzymic preparation of L-glutamine and L-asparagine deamidase was obtained from Pseudomonas auractiaca IBPM B-14. The preparation was purified 100--150-fold by thermal treatment and chromotography on columns with biogel P-150 and DEAE-cellulose. The enzymic activity was measured by the methods of hydroxylaminolysis and direct nesslerization. The deamidase preparation had an activity of 51 i. u. by glutamine and 15 i. e. by asparagine. Evidence on the pH effect on the deamidase activity was accumulated."}
{"id": "PMID:10573", "title": "Use of thyrotropin and cholera toxin to probe the mechanism by which interferon initiates its antiviral activity.", "content": "Thyrotropin (10 muM) inhibited the antiviral activity of interferon. When added after interferon, thyrotropin (TSH) had no effect on antiviral activity. There was also no inhibition of interferon action in cells washed with medium between incubations with TSH and interferon. 125I-Labeled TSH and 125I-labeled cholera toxin could bind to preparations of mouse L-cell plasma membranes. The binding was specific in that it was prevented by unlabeled thyrotropin or cholera toxin, but not by insulin, glucagon, prolactin, growth hormone, human chorionic gonadotropin, or luteinizing hormone. Mouse interferon inhibited 125I-labeled TSH binding to L-cell plasma membranes. The effect of mouse interferon on 125I-labeled cholera toxon binding was more complex, inhibition occurring only after an initial enhancement at low interferon concentrations. A 10-fold higher concentration of interferon was required to inhibit 125I-labeled TSH binding. Mouse interferon was also able to displace bound 125I-labeled TSH, but not bound 125I-labeled cholera toxin. The interferon interaction with cell membranes was temperature-sensitive. Human interferon could induce changes in binding of 125I-labeled TSH and 125I-labeled cholera toxin to mouse L-cell plasma membranes similar to those induced by mouse interferon. Mouse interferon induced similar changes in plasma membranes of human KB-3 cells, which are insensitive to both human and mouse interferons. In view of these results, the species specificity of interferons does not appear to reside solely at the point of the initial interaction with their binding sites.", "contents": "Use of thyrotropin and cholera toxin to probe the mechanism by which interferon initiates its antiviral activity. Thyrotropin (10 muM) inhibited the antiviral activity of interferon. When added after interferon, thyrotropin (TSH) had no effect on antiviral activity. There was also no inhibition of interferon action in cells washed with medium between incubations with TSH and interferon. 125I-Labeled TSH and 125I-labeled cholera toxin could bind to preparations of mouse L-cell plasma membranes. The binding was specific in that it was prevented by unlabeled thyrotropin or cholera toxin, but not by insulin, glucagon, prolactin, growth hormone, human chorionic gonadotropin, or luteinizing hormone. Mouse interferon inhibited 125I-labeled TSH binding to L-cell plasma membranes. The effect of mouse interferon on 125I-labeled cholera toxon binding was more complex, inhibition occurring only after an initial enhancement at low interferon concentrations. A 10-fold higher concentration of interferon was required to inhibit 125I-labeled TSH binding. Mouse interferon was also able to displace bound 125I-labeled TSH, but not bound 125I-labeled cholera toxin. The interferon interaction with cell membranes was temperature-sensitive. Human interferon could induce changes in binding of 125I-labeled TSH and 125I-labeled cholera toxin to mouse L-cell plasma membranes similar to those induced by mouse interferon. Mouse interferon induced similar changes in plasma membranes of human KB-3 cells, which are insensitive to both human and mouse interferons. In view of these results, the species specificity of interferons does not appear to reside solely at the point of the initial interaction with their binding sites."}
{"id": "PMID:10574", "title": "Multiple factor analysis of the action of local anesthetics.", "content": "The pH jump data of Bianchi and Strobel [(1968) Trans. N.Y. Acad. Sci. Ser. II, 30, 1082-1092] on desheathed frog sciatic nerve are fitted to rate equations. A general quantitation of synergism, summation, and antagonism of anesthetics and of excitation is given.", "contents": "Multiple factor analysis of the action of local anesthetics. The pH jump data of Bianchi and Strobel [(1968) Trans. N.Y. Acad. Sci. Ser. II, 30, 1082-1092] on desheathed frog sciatic nerve are fitted to rate equations. A general quantitation of synergism, summation, and antagonism of anesthetics and of excitation is given."}
{"id": "PMID:10575", "title": "Rumen function in red deer, hill sheep and reindeer in the scottish highlands.", "content": "Red deer, sheep and reindeer grazing on their normal hill ranges were examined at intervals over a period of four years. Samples from the digestive tract were taken at different seasons and processed in the field. The Red deer and reindeer were killed before samples were taken; rumen samples from the sheep were taken by stomach tube, but a number of animals were also killed at different seasons to correlate stomach tube and whole rumen samples. The animals sampled were representative of the general condition of the herds. Examinations were made for parasites and any pathological conditions. In most instances parasitic infections were slight. Apparent seasonal changes were found in the compositions of the diets. The Red deer and sheep ate principally heather and grass, the proportion of heather increasing in the winter. The reindeer ate mainly grass in the summer, with lichens and grass forming the winter diet, and these animals seemed to have a higher nutritional status in the winter than did the other two species. The weights of the animals and of their rumen contents, the concentrations of rumen ammonia and volatile fatty acid, and the rates at which different dietary components were fermented are recorded. Rumen fermentation was low in winter and the diets were generally inadequate for the animals. A lack of nitrogen seemed to be a major factor. Some data on caecal contents are also given.", "contents": "Rumen function in red deer, hill sheep and reindeer in the scottish highlands. Red deer, sheep and reindeer grazing on their normal hill ranges were examined at intervals over a period of four years. Samples from the digestive tract were taken at different seasons and processed in the field. The Red deer and reindeer were killed before samples were taken; rumen samples from the sheep were taken by stomach tube, but a number of animals were also killed at different seasons to correlate stomach tube and whole rumen samples. The animals sampled were representative of the general condition of the herds. Examinations were made for parasites and any pathological conditions. In most instances parasitic infections were slight. Apparent seasonal changes were found in the compositions of the diets. The Red deer and sheep ate principally heather and grass, the proportion of heather increasing in the winter. The reindeer ate mainly grass in the summer, with lichens and grass forming the winter diet, and these animals seemed to have a higher nutritional status in the winter than did the other two species. The weights of the animals and of their rumen contents, the concentrations of rumen ammonia and volatile fatty acid, and the rates at which different dietary components were fermented are recorded. Rumen fermentation was low in winter and the diets were generally inadequate for the animals. A lack of nitrogen seemed to be a major factor. Some data on caecal contents are also given."}
{"id": "PMID:10577", "title": "Modulation of cycloheximide-resistant memory by sympathomimetic agents.", "content": "Amphetamine overcomes the amnesia caused by cycloheximide (CXM) provided it is administered closely following the learning trial. In day-old chickens with one trial passive avoidance learning, there is a short-term, labile memory existing for 90 min following training under the influence of CXM. Amphetamine has been shown to keep the memory at precisely the level exhibited by the labile, cycloheximide-resistant memory trace at the time of injection. Norepinephrine, methoxamine (an alpha adrenergic stimulant) and isoprenaline (a beta adrenergic stimulant) each mimic the amphetamine effect in CXM-pretreated chickens. That the action of amphetamine could be due to its release of norepinephrine is supported by the finding that it could be blocked by both alpha adrenergic (piperoxane) and beta adrenergic antagonists (propranolol). It has been suggested that this labile memory trace depends on the functioning of a sodium pump. Norepinephrine may be modulating memory formation by an action on the sodium pump since in preliminary biochemical assays norepinephrine stimulated the sodium pump (Na+/K+ ATPase) activity in chicken forebrain total homogenate.", "contents": "Modulation of cycloheximide-resistant memory by sympathomimetic agents. Amphetamine overcomes the amnesia caused by cycloheximide (CXM) provided it is administered closely following the learning trial. In day-old chickens with one trial passive avoidance learning, there is a short-term, labile memory existing for 90 min following training under the influence of CXM. Amphetamine has been shown to keep the memory at precisely the level exhibited by the labile, cycloheximide-resistant memory trace at the time of injection. Norepinephrine, methoxamine (an alpha adrenergic stimulant) and isoprenaline (a beta adrenergic stimulant) each mimic the amphetamine effect in CXM-pretreated chickens. That the action of amphetamine could be due to its release of norepinephrine is supported by the finding that it could be blocked by both alpha adrenergic (piperoxane) and beta adrenergic antagonists (propranolol). It has been suggested that this labile memory trace depends on the functioning of a sodium pump. Norepinephrine may be modulating memory formation by an action on the sodium pump since in preliminary biochemical assays norepinephrine stimulated the sodium pump (Na+/K+ ATPase) activity in chicken forebrain total homogenate."}
{"id": "PMID:10578", "title": "Studies on the polymorphism of carbromal.", "content": "Specimens of carbromal obtained by crystallization from various solvents were analyzed. After a 9-month storage period, the occurrence of three polymorphic forms (I, II and III) was ascertained. The metastable form III obtained by crystallization from dimethylformamide showed a reasonably high stability. Preliminary pharmacological tests revealed clear-cut differences in the therapeutic effect between a commercial specimen and the polymorphic modification III. The results presented here indicate the importance of polymorphism of carbromal for medicinal use.", "contents": "Studies on the polymorphism of carbromal. Specimens of carbromal obtained by crystallization from various solvents were analyzed. After a 9-month storage period, the occurrence of three polymorphic forms (I, II and III) was ascertained. The metastable form III obtained by crystallization from dimethylformamide showed a reasonably high stability. Preliminary pharmacological tests revealed clear-cut differences in the therapeutic effect between a commercial specimen and the polymorphic modification III. The results presented here indicate the importance of polymorphism of carbromal for medicinal use."}
{"id": "PMID:10583", "title": "Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects.", "content": "A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.", "contents": "Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects. A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored."}
{"id": "PMID:10584", "title": "The contribution of drug research to investigating the nature of endogenous depression.", "content": "A relationship between brain monamines and endogenous depression is suggested by observations on the mode of action of drugs producing or alleviating depressive symptoms. For example, reserpine is capable of faithfully mimicking the clinical picture of endogenous depression, which may be related to monoamine depletion. On the other hand, antidepressant drugs, e.g. the monoamine oxidase inhibitors, the tricyclic antidepressants and the monoamine precursors appear to increase the availability of monoamines at postsynaptic receptor sites. The different classes of antidepressant agents in general appear to potentiate each other's actions, according to animal data and clinical observations. Studies on the mode of action of tricyclic antidepressants with different profiles and on monoamine precursors suggest that 5-hydroxytryptamine is primarily involved in the control of mood, and noradrenaline in psychomotor activity. Clincial investigations initiated by the drug studies have demonstrated changes in monoamine metabolism in endogenous depression. The available evidence thus suggests a causal relationship between disturbances in monoamine metabolism and depression.", "contents": "The contribution of drug research to investigating the nature of endogenous depression. A relationship between brain monamines and endogenous depression is suggested by observations on the mode of action of drugs producing or alleviating depressive symptoms. For example, reserpine is capable of faithfully mimicking the clinical picture of endogenous depression, which may be related to monoamine depletion. On the other hand, antidepressant drugs, e.g. the monoamine oxidase inhibitors, the tricyclic antidepressants and the monoamine precursors appear to increase the availability of monoamines at postsynaptic receptor sites. The different classes of antidepressant agents in general appear to potentiate each other's actions, according to animal data and clinical observations. Studies on the mode of action of tricyclic antidepressants with different profiles and on monoamine precursors suggest that 5-hydroxytryptamine is primarily involved in the control of mood, and noradrenaline in psychomotor activity. Clincial investigations initiated by the drug studies have demonstrated changes in monoamine metabolism in endogenous depression. The available evidence thus suggests a causal relationship between disturbances in monoamine metabolism and depression."}
{"id": "PMID:10585", "title": "Indications for long-term pharmacological treatment of schizophrenic syndromes.", "content": "The practice of long term pharmacological treatment of schizophrenic syndromes has become widespread and seems to be currently recommended. The concept appears, however, to be poorly defined, and the assumptions underlying this therapeutic approach are scarcely discussed. In the present paper possible differences as concerns the hypotheses which might motivate a long term pharmacological treatment are schetched and their possible implications discussed. A short review of factors which might influence the decision for long term pharmacological treatment is also presented. Finally some recommendations for an appropriate management of long term psychopharmacological treatment are suggested.", "contents": "Indications for long-term pharmacological treatment of schizophrenic syndromes. The practice of long term pharmacological treatment of schizophrenic syndromes has become widespread and seems to be currently recommended. The concept appears, however, to be poorly defined, and the assumptions underlying this therapeutic approach are scarcely discussed. In the present paper possible differences as concerns the hypotheses which might motivate a long term pharmacological treatment are schetched and their possible implications discussed. A short review of factors which might influence the decision for long term pharmacological treatment is also presented. Finally some recommendations for an appropriate management of long term psychopharmacological treatment are suggested."}
{"id": "PMID:10586", "title": "Critical study of the use of long acting neuroleptics (depot neuroleptics) in France.", "content": "Long acting neuroleptics (L.A.N.) represent 11% of the medical prescription of neuroleptics in France (about 40,000 patients in 1974). Some psychiatrists remain reluctant to prescribe long acting-neuroleptics and many problems related to their use are still solved empirically:1) relation between the posology of the standard Neuroleptic and the corresponding L.A.N. 2)the problem of dose-interval. 3) the necessary prescription of an parkinsonian. The superiority of N.A.P. over the Neuroleptic Standard has received no experimental confirmation in France, but the L.A.N. appear to us as an original therapy, the \"pivot chemotherapy\" around which psychotherapy and sociotherapy can be arranged without anarchical and ceaseless changes of neuroleptic compounds and of posology.", "contents": "Critical study of the use of long acting neuroleptics (depot neuroleptics) in France. Long acting neuroleptics (L.A.N.) represent 11% of the medical prescription of neuroleptics in France (about 40,000 patients in 1974). Some psychiatrists remain reluctant to prescribe long acting-neuroleptics and many problems related to their use are still solved empirically:1) relation between the posology of the standard Neuroleptic and the corresponding L.A.N. 2)the problem of dose-interval. 3) the necessary prescription of an parkinsonian. The superiority of N.A.P. over the Neuroleptic Standard has received no experimental confirmation in France, but the L.A.N. appear to us as an original therapy, the \"pivot chemotherapy\" around which psychotherapy and sociotherapy can be arranged without anarchical and ceaseless changes of neuroleptic compounds and of posology."}
{"id": "PMID:10587", "title": "Unwanted effects of long-term medication in schizophrenia and depression.", "content": "Medicine is an experimental science which proceeds by trial and error, and with pharmacotherapy doctors must continually review the drugs at their disposal for both effectiveness and adverse effects. These adverse effects must be assessed not only in relation to the therapeutic effect, but also, of course, in relation to the severity of the patient's illness and the likely prognosis in the absence of treatment. In this review I will select one or two side effects in each of the major group of drugs for consideration.", "contents": "Unwanted effects of long-term medication in schizophrenia and depression. Medicine is an experimental science which proceeds by trial and error, and with pharmacotherapy doctors must continually review the drugs at their disposal for both effectiveness and adverse effects. These adverse effects must be assessed not only in relation to the therapeutic effect, but also, of course, in relation to the severity of the patient's illness and the likely prognosis in the absence of treatment. In this review I will select one or two side effects in each of the major group of drugs for consideration."}
{"id": "PMID:10589", "title": "Malaria of the orang-utan (Pongo pygmaeus) in Borneo.", "content": "The primary objective of this project was to study the life cycle and ecology of Plasmodium pitheci, a malaria parasite of the orang-utan. The field work was based on the orang-utan rehabilitation centre in the Sepilok Forest Reserve of eastern Sabah. Two visits were made to Sepilok, the first in February and March, 1972, and the second (by W.P.) in January 1974. On the first visit two species of \"surrogate host\" were taken to Sabah, i.e. chimpanzees and Aotus monkeys for experimental work. The arboreal habitat of the orang-utan in the dipterocarp forests of eastern Sabah is described. In the Sepilok Forest Reserve dwell gibbons and leaf-monkeys, in addition to a small population of semi-domesticated and wild, free-ranging orang-utans of various ages. Although numerous species of anopheline mosquitoes have been collected in eastern Sabah, longitudinal studies are not available. Anopheles balabacensis was caught both attracted to orang-utans and to man at Sepilok. This species which is the main vector of human malaria in the north of Borneo, is suspected also of transmitting orang-utan malaria in this part of Sabah. Repeated blood examinations have been made on a number of orang-utans in the centre since 1966 and a high prevalence of infection was recorded with Plasmodium pitheci. In 1966 10 out of 19 animals had demonstrable parasitaemia. Detailed case histories are presented to show the course of parasitaemia in several orang-utans. Infections of P. pitheci were found to run a very chronic course. During the 1972 expedition a second, previously undescribed malaria parasite of the orang-utan was discovered, and was named P. silvaticum. The new parasite was successfully transmitted both by blood inoculation and, later, by sporozoite inoculation, into splenectomized chimpanzees. Although both species of malaria parasite may cause transitory signs of illness, orang-utans in general appear to be little discomforted by the infection. The animals do however suffer from other infectious diseases such as amoebic and balantidial dysentery, and melioidosis is a serious natural hazard which may have accounted for several deaths of wild orang-utans. An unidentified, intraerythrocytic structure that appeared in the blood of one chimpanzee, which had been inoculated with blood from an orang-utan, may have contributed to its death. Detailed descriptions and illustrations of P. pitheci and P. silvaticum are given. All stages of the life cycle of P. silvaticum are known (the tissue stages having been described in the liver of a \"surrogate host\", the chimpanzee) but only the blood and sporogonic stages of P. pitheci have been seen. This species was not infective to a chimpanzee, although there is an earlier report of a transient infection in this host by other workers. In the blood both parasites showed a tertian periodicity. From the appearance of the tissue schizonts on the seventh day it was estimated that the complete pre-erythrocytic cycle of P. silvaticum in the chimpanzee would occupy 8 days. P...", "contents": "Malaria of the orang-utan (Pongo pygmaeus) in Borneo. The primary objective of this project was to study the life cycle and ecology of Plasmodium pitheci, a malaria parasite of the orang-utan. The field work was based on the orang-utan rehabilitation centre in the Sepilok Forest Reserve of eastern Sabah. Two visits were made to Sepilok, the first in February and March, 1972, and the second (by W.P.) in January 1974. On the first visit two species of \"surrogate host\" were taken to Sabah, i.e. chimpanzees and Aotus monkeys for experimental work. The arboreal habitat of the orang-utan in the dipterocarp forests of eastern Sabah is described. In the Sepilok Forest Reserve dwell gibbons and leaf-monkeys, in addition to a small population of semi-domesticated and wild, free-ranging orang-utans of various ages. Although numerous species of anopheline mosquitoes have been collected in eastern Sabah, longitudinal studies are not available. Anopheles balabacensis was caught both attracted to orang-utans and to man at Sepilok. This species which is the main vector of human malaria in the north of Borneo, is suspected also of transmitting orang-utan malaria in this part of Sabah. Repeated blood examinations have been made on a number of orang-utans in the centre since 1966 and a high prevalence of infection was recorded with Plasmodium pitheci. In 1966 10 out of 19 animals had demonstrable parasitaemia. Detailed case histories are presented to show the course of parasitaemia in several orang-utans. Infections of P. pitheci were found to run a very chronic course. During the 1972 expedition a second, previously undescribed malaria parasite of the orang-utan was discovered, and was named P. silvaticum. The new parasite was successfully transmitted both by blood inoculation and, later, by sporozoite inoculation, into splenectomized chimpanzees. Although both species of malaria parasite may cause transitory signs of illness, orang-utans in general appear to be little discomforted by the infection. The animals do however suffer from other infectious diseases such as amoebic and balantidial dysentery, and melioidosis is a serious natural hazard which may have accounted for several deaths of wild orang-utans. An unidentified, intraerythrocytic structure that appeared in the blood of one chimpanzee, which had been inoculated with blood from an orang-utan, may have contributed to its death. Detailed descriptions and illustrations of P. pitheci and P. silvaticum are given. All stages of the life cycle of P. silvaticum are known (the tissue stages having been described in the liver of a \"surrogate host\", the chimpanzee) but only the blood and sporogonic stages of P. pitheci have been seen. This species was not infective to a chimpanzee, although there is an earlier report of a transient infection in this host by other workers. In the blood both parasites showed a tertian periodicity. From the appearance of the tissue schizonts on the seventh day it was estimated that the complete pre-erythrocytic cycle of P. silvaticum in the chimpanzee would occupy 8 days. P..."}
{"id": "PMID:10591", "title": "Different susceptibilities to intracellular proteases of hemoglobin and hemoglobin-haptoglobin complex.", "content": "The susceptibilities of hemoglobin and hemoglobin-haptoglobin complex to intracellular proteases differ significantly. Hemoglobin and hemoglobin-haptoglobin complex are degested in the regions of pH 5.5-2.5 and 4.0-2.5 respectively, having pH optima at pH 4.0 and 3.0 respectively, by intracellular proteases from rat and mouse liver or spleen. The difference in proteolytic susceptibility is found to be due to the different stabilities to acid among hemoglobin derivatives as evidenced by the measurements of their helical contents in acidic pH.", "contents": "Different susceptibilities to intracellular proteases of hemoglobin and hemoglobin-haptoglobin complex. The susceptibilities of hemoglobin and hemoglobin-haptoglobin complex to intracellular proteases differ significantly. Hemoglobin and hemoglobin-haptoglobin complex are degested in the regions of pH 5.5-2.5 and 4.0-2.5 respectively, having pH optima at pH 4.0 and 3.0 respectively, by intracellular proteases from rat and mouse liver or spleen. The difference in proteolytic susceptibility is found to be due to the different stabilities to acid among hemoglobin derivatives as evidenced by the measurements of their helical contents in acidic pH."}
{"id": "PMID:10592", "title": "Mechanoelectrical transduction in hyaluronic acid salt solution is an entropy-driven process.", "content": "An electrical potential develops between the ends of a column of hyaluronic salt solution displaced from a resting position by gentle pressure. A previous study demonstrated that such displacement changes the optical rotary dispersion properties of the salt, either increasing the rotation in the direction already shown by the salt before displacement or changing and increasing the rotation in the opposite direction, depending on the direction of the displacement. The present investigation demonstrates that the loss of bound water component across a membrane separating the solution and water is corelated with the extent of the column displacement. In addition, a return of the column to the position before displacement is correlated with a return of the water component across the membrane-but not at the same rate as the exodus. The data seem consistent with the hypothesis that the hyaluronic acid salt, when strained, adopts a less entropic configuration, releasing bound water and thus increasing the  entropy of water component. This change in the distribution of entropy is reversible; i.e., Eddington's \"time's arrow\" is reversible with respect to the water component of the solution.", "contents": "Mechanoelectrical transduction in hyaluronic acid salt solution is an entropy-driven process. An electrical potential develops between the ends of a column of hyaluronic salt solution displaced from a resting position by gentle pressure. A previous study demonstrated that such displacement changes the optical rotary dispersion properties of the salt, either increasing the rotation in the direction already shown by the salt before displacement or changing and increasing the rotation in the opposite direction, depending on the direction of the displacement. The present investigation demonstrates that the loss of bound water component across a membrane separating the solution and water is corelated with the extent of the column displacement. In addition, a return of the column to the position before displacement is correlated with a return of the water component across the membrane-but not at the same rate as the exodus. The data seem consistent with the hypothesis that the hyaluronic acid salt, when strained, adopts a less entropic configuration, releasing bound water and thus increasing the  entropy of water component. This change in the distribution of entropy is reversible; i.e., Eddington's \"time's arrow\" is reversible with respect to the water component of the solution."}
{"id": "PMID:10599", "title": "Necroqizing enterocolitis with pneumatosis intestinalis in systemic lupus erythematosus and polyarteritis.", "content": "Pneumatosis intestinalis was encountered in association with fatal necrotizing enterocolitis in systemic lupus erythematosus (SLE) and polyarteritis nodosa. The radiologic identification of mottled, bubbly, and linear collections of intramural intestinal gas distinguish this ominous complication from benign pneumatosis cystoides intestinalis. In the setting of intestinal vasculitis due to SLE or polyarteritis nodosa, these characteristic radiologic features indicate necrotizing enterocolitis. Since corticosteroids may mask clinical progression of the intestinal lesion, radiologic evaluation is essential in the overall management of the patient with intestinal vasculitis.", "contents": "Necroqizing enterocolitis with pneumatosis intestinalis in systemic lupus erythematosus and polyarteritis. Pneumatosis intestinalis was encountered in association with fatal necrotizing enterocolitis in systemic lupus erythematosus (SLE) and polyarteritis nodosa. The radiologic identification of mottled, bubbly, and linear collections of intramural intestinal gas distinguish this ominous complication from benign pneumatosis cystoides intestinalis. In the setting of intestinal vasculitis due to SLE or polyarteritis nodosa, these characteristic radiologic features indicate necrotizing enterocolitis. Since corticosteroids may mask clinical progression of the intestinal lesion, radiologic evaluation is essential in the overall management of the patient with intestinal vasculitis."}
{"id": "PMID:10602", "title": "Biochemical properties of the prostaglandin/thromboxane synthetase of human blood platelets and comparison with the synthetase of bovine seminal vesicles.", "content": "The enzyme system which  synthesizes prostaglandins and thromboxanes in extracts of washed human platelets has been characterized with respect to kinetic parameters, pH and cofactor dependence, and inhibitor potencies. Arachidonate and dihomo-gamma-linolenate were shown to be mutually competitive substrates, thus providing biochemical support for the assumption that both substrates are metabolized by the same cyclooxygenase, although they are ultimately metabolized to different patterns of products. Products of the synthetase of human leucocytes qualitatively resemble those obtained with human platelets. The prostaglandin synthetase of bovine seminal vesicles was studied under similar conditions, and kinetic parameters and inhibitor potencies were compared with those of platelet extracts.", "contents": "Biochemical properties of the prostaglandin/thromboxane synthetase of human blood platelets and comparison with the synthetase of bovine seminal vesicles. The enzyme system which  synthesizes prostaglandins and thromboxanes in extracts of washed human platelets has been characterized with respect to kinetic parameters, pH and cofactor dependence, and inhibitor potencies. Arachidonate and dihomo-gamma-linolenate were shown to be mutually competitive substrates, thus providing biochemical support for the assumption that both substrates are metabolized by the same cyclooxygenase, although they are ultimately metabolized to different patterns of products. Products of the synthetase of human leucocytes qualitatively resemble those obtained with human platelets. The prostaglandin synthetase of bovine seminal vesicles was studied under similar conditions, and kinetic parameters and inhibitor potencies were compared with those of platelet extracts."}
{"id": "PMID:10603", "title": "Tardive dyskinesia and depressive illness.", "content": "Tardive dyskinesia has been regarded as a long-term complication of neuroleptic administration to patients with the diagnosis of schizophrenia. However, nine of the first fourteen patients evaluated for an investigation of tardive dyskinesia met diagnostic criteria for depression. Neuroleptics produce blockade of post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Chronically decreased neurotransmission in the synapse of a patient with depression may contribute to the development of a super-sensitive receptor and could explain the high proportion of patients with depression seen in this sample of patients with tardive dyskinesia.", "contents": "Tardive dyskinesia and depressive illness. Tardive dyskinesia has been regarded as a long-term complication of neuroleptic administration to patients with the diagnosis of schizophrenia. However, nine of the first fourteen patients evaluated for an investigation of tardive dyskinesia met diagnostic criteria for depression. Neuroleptics produce blockade of post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Chronically decreased neurotransmission in the synapse of a patient with depression may contribute to the development of a super-sensitive receptor and could explain the high proportion of patients with depression seen in this sample of patients with tardive dyskinesia."}
{"id": "PMID:10604", "title": "Weight-bearing deficiency of the 1st metatarsal ray.", "content": "The authors have analysed a special disturbance of the statics and dynamics of the forefoot - deficient weight-bearing on the first metatarsal ray whilst walking. From the clinical point of view, the condition resulted in the development of a dorsal bunion and metatarsalgia. Forty-nine cases were treated and seven causative factors were discovered: Club foot, Paralysis, Congenital deformity, Fracture-dislocation of Lisfranc's joint, Sequelae of surgery for hallux valgus, Sequelae of subtaler arthrodesis, \"Functional\" abnormality.", "contents": "Weight-bearing deficiency of the 1st metatarsal ray. The authors have analysed a special disturbance of the statics and dynamics of the forefoot - deficient weight-bearing on the first metatarsal ray whilst walking. From the clinical point of view, the condition resulted in the development of a dorsal bunion and metatarsalgia. Forty-nine cases were treated and seven causative factors were discovered: Club foot, Paralysis, Congenital deformity, Fracture-dislocation of Lisfranc's joint, Sequelae of surgery for hallux valgus, Sequelae of subtaler arthrodesis, \"Functional\" abnormality."}
{"id": "PMID:10605", "title": "Measurement of glycolytic rates in cell suspensions using a recording pH meter.", "content": "A method for measuring continuously glycolytic rates in cell suspensions, using a recording pH meter, is described. Under the described conditions the method is very exact, sensitive and reproducible. The method can be applied to different cells and different conditions of assay calibrating in each case the pH range, cell concentration range and the ratio of delta protons to delta lactic acid.", "contents": "Measurement of glycolytic rates in cell suspensions using a recording pH meter. A method for measuring continuously glycolytic rates in cell suspensions, using a recording pH meter, is described. Under the described conditions the method is very exact, sensitive and reproducible. The method can be applied to different cells and different conditions of assay calibrating in each case the pH range, cell concentration range and the ratio of delta protons to delta lactic acid."}
{"id": "PMID:10606", "title": "Characterization and induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in rabbit bone marrow.", "content": "Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered.", "contents": "Characterization and induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase in rabbit bone marrow. Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered."}
{"id": "PMID:10607", "title": "NADPH dependent lipid peroxidation of calcium bound microsomes.", "content": "Rat liver microsomes prepared by a calcium aggregation method have been found capable of readily undergoing NADPH induced lipid peroxidation. Malonic dialdehyde production of calcium bound microsomes is equivalent to that attained by microsomes prepared by ultracentrifugation. In addition these calcium bound microsomes can be quickly removed from suspension by means of ultrafiltration.", "contents": "NADPH dependent lipid peroxidation of calcium bound microsomes. Rat liver microsomes prepared by a calcium aggregation method have been found capable of readily undergoing NADPH induced lipid peroxidation. Malonic dialdehyde production of calcium bound microsomes is equivalent to that attained by microsomes prepared by ultracentrifugation. In addition these calcium bound microsomes can be quickly removed from suspension by means of ultrafiltration."}
{"id": "PMID:10608", "title": "Molecular complexes of cocaine, its active metabolites and some other stimulants with thiamine.", "content": "Cocaine, its pharmacologically active metabolites, norcocaine benzoylnorecgonine, benzoylecgonine and other central nervous system stimulants e.g. dextrococaine, nicotine, caffeine and p-hydroxy norephedrine formed molecular complexes with thiamine. The possible implications of such an interaction are discussed.", "contents": "Molecular complexes of cocaine, its active metabolites and some other stimulants with thiamine. Cocaine, its pharmacologically active metabolites, norcocaine benzoylnorecgonine, benzoylecgonine and other central nervous system stimulants e.g. dextrococaine, nicotine, caffeine and p-hydroxy norephedrine formed molecular complexes with thiamine. The possible implications of such an interaction are discussed."}
{"id": "PMID:10609", "title": "[Immune status of indefinitely surviving rat renal allograft recipients after short course of ALS-treatment Detection of a serum blocking factor by allorosette formation inhibition test (author's transl)].", "content": "53 LBNF1 kidneys were grafted into L-rats. 24 untreated recipients served as control and survived 16.1 +/- 1.7 days. 14 recipients were treated with 4 ml alloantiserum (ADS) each, and the other 15 animals with 4 ml ALS each. 9 and 10 of these 14 and 15 animals survived for more than 4 months. We performed GvH-reaction with spleen cells of these 19 animals. It showed normal cellular immune response. After splenectomy first donor specific skin was transplanted, 18 days later second skin of same origin (LBNF1) and 18' days after third party skin (LBufF1). The first grafts survived 13.1 +/- 1.9 days in the recipients of ADS treatment and 12.2 +/- 1.2 days in the recipients of ALS. Second skin grafts were rejected delayed in the former recipients as the first grafts, in the later more accelerated than the first grafts. The third grafts survived as the controls. Before and after skin grafting we could not detect lymphocytotoxin and hemagglutinin. The sera of animals with ADS therapy inhibited the spontaneous allorosette formation to 46.0 +/- 4.4% and of ALS therapy 37.7 +/- 9.2%. Our results suggest that after ALS treatment blocking antibodies were produced in the recipients and they cause the enhancement of kidney allograft.", "contents": "[Immune status of indefinitely surviving rat renal allograft recipients after short course of ALS-treatment Detection of a serum blocking factor by allorosette formation inhibition test (author's transl)]. 53 LBNF1 kidneys were grafted into L-rats. 24 untreated recipients served as control and survived 16.1 +/- 1.7 days. 14 recipients were treated with 4 ml alloantiserum (ADS) each, and the other 15 animals with 4 ml ALS each. 9 and 10 of these 14 and 15 animals survived for more than 4 months. We performed GvH-reaction with spleen cells of these 19 animals. It showed normal cellular immune response. After splenectomy first donor specific skin was transplanted, 18 days later second skin of same origin (LBNF1) and 18' days after third party skin (LBufF1). The first grafts survived 13.1 +/- 1.9 days in the recipients of ADS treatment and 12.2 +/- 1.2 days in the recipients of ALS. Second skin grafts were rejected delayed in the former recipients as the first grafts, in the later more accelerated than the first grafts. The third grafts survived as the controls. Before and after skin grafting we could not detect lymphocytotoxin and hemagglutinin. The sera of animals with ADS therapy inhibited the spontaneous allorosette formation to 46.0 +/- 4.4% and of ALS therapy 37.7 +/- 9.2%. Our results suggest that after ALS treatment blocking antibodies were produced in the recipients and they cause the enhancement of kidney allograft."}
{"id": "PMID:10610", "title": "[The G\u00f6ttinger minipig as a laboratory animal (author's transl)].", "content": "Blood pictures, serumelectrolytes, acid-base- and bloodgas-values of the arterial blood were determined from two juvenile and one adulte collectives of minipigs (Gottingen strain), which were kept under SPF-conditions. The results were compared with the corresponding values of human blood and should be regarded as base- or orienting values for further investigations.", "contents": "[The G\u00f6ttinger minipig as a laboratory animal (author's transl)]. Blood pictures, serumelectrolytes, acid-base- and bloodgas-values of the arterial blood were determined from two juvenile and one adulte collectives of minipigs (Gottingen strain), which were kept under SPF-conditions. The results were compared with the corresponding values of human blood and should be regarded as base- or orienting values for further investigations."}
{"id": "PMID:10611", "title": "[Studies on the pH-dependence, inhibition and reactivation of angiotension II-amide splitting enzymes in human erythrocytes (author's transl)].", "content": "Aminopeptidase activity of three fractions of human erythrocytes (membranes free of hemoglobin; hemolysate free of membranes; enzyme protein fraction made free of hemoglobin by DEAE-cellulose) was measured by a NADH dependent optical test using asparaginyl1-angiotension II-amide as substrate. 1. From the enzyme protein fraction 6 subfractions were obtained by (NH4)2SO4 precipitation. By measuring enzyme kinetics at three different pH-values (pH 5,0; 7,0; 8,0) with and without addition of the effectors Na2EDTA and Ca++ the existence of 6 different enzymes could be demonstrated. 2. The aminopeptidase activity of the hemolysate made free of membranes could be inhibited by diisopropylfluorphosphate and p-chloromercuribenzoate at three different pH-values (pH 5,0; 6,5; 7,0; 8,0 and 6,5; 7,0; 8,0 respectively). 3. A reduction of enzymatic activity of 20% was found after incubation at 37degreesC for two hours.", "contents": "[Studies on the pH-dependence, inhibition and reactivation of angiotension II-amide splitting enzymes in human erythrocytes (author's transl)]. Aminopeptidase activity of three fractions of human erythrocytes (membranes free of hemoglobin; hemolysate free of membranes; enzyme protein fraction made free of hemoglobin by DEAE-cellulose) was measured by a NADH dependent optical test using asparaginyl1-angiotension II-amide as substrate. 1. From the enzyme protein fraction 6 subfractions were obtained by (NH4)2SO4 precipitation. By measuring enzyme kinetics at three different pH-values (pH 5,0; 7,0; 8,0) with and without addition of the effectors Na2EDTA and Ca++ the existence of 6 different enzymes could be demonstrated. 2. The aminopeptidase activity of the hemolysate made free of membranes could be inhibited by diisopropylfluorphosphate and p-chloromercuribenzoate at three different pH-values (pH 5,0; 6,5; 7,0; 8,0 and 6,5; 7,0; 8,0 respectively). 3. A reduction of enzymatic activity of 20% was found after incubation at 37degreesC for two hours."}
{"id": "PMID:10613", "title": "Carbonic anhydrase inhibitor in trout plasma.", "content": "A manometric assay has been constructed such that carbonic anhydrase dehydration activity can be determined utilizing intact erythrocytes. It was found that unwashed whole trout blood lacks any dehydration activity quite in contrast to whole rat blood. Removal of the plasma and replacement with physiological saline results in pronounced dehydration activity with inhibition restored by replacing the saline with the original plasma. An inhibitor residing in the plasma (probably a protein but not yet fully characterized) is capable of limiting in vivo dehydration activity. The inhibitor could work at the level of the enzyme per se or by inhibiting erythrocytic HCO3 influx, or both. The lack of erythrocytic dehydration activity presumably would alter CO2 excretion patterns; possible implications are discussed.", "contents": "Carbonic anhydrase inhibitor in trout plasma. A manometric assay has been constructed such that carbonic anhydrase dehydration activity can be determined utilizing intact erythrocytes. It was found that unwashed whole trout blood lacks any dehydration activity quite in contrast to whole rat blood. Removal of the plasma and replacement with physiological saline results in pronounced dehydration activity with inhibition restored by replacing the saline with the original plasma. An inhibitor residing in the plasma (probably a protein but not yet fully characterized) is capable of limiting in vivo dehydration activity. The inhibitor could work at the level of the enzyme per se or by inhibiting erythrocytic HCO3 influx, or both. The lack of erythrocytic dehydration activity presumably would alter CO2 excretion patterns; possible implications are discussed."}
{"id": "PMID:10614", "title": "Intracellular pH in cold-blooded vertebrates as a function of body temperature.", "content": "Intracellular pH (pHi) was measured in vivo in tissue of frogs (Rana catesbeiana) and turtles (Pseudemys scripta) using the DMO technique. Animals were permitted 3-8 days to come to a new steady-state body temperature (Tb) which ranged 5-32 degrees C. Least squares regression equation for pHi data are: frog blood, 8.184-0.0206 Tb; frog striated muscle, 7.275-0.0152 Tb; turtle blood, 8.092-0.0207Tb; turtle muscle, 7.421-0.0186 Tb; turtle heart, 7.452-0.0122 Tb; turtle liver, 7.753-0.0233 Tb; turtle esophageal smooth muscle, 7.513-0.0141 Tb. Only turtle cardiac muscle deltapHi/deltaT was significantly different from deltapH/deltaT of blood. Results have been interpreted in terms of protein charge state alterations; in the physiological pH range, histidine residues of proteins are the principal dissociable groups (HPr+ = H+ + Pr) affected by pHi and Tb changes. Constancy of protein charge state can be assessed by monitoring alpha imidazole, alphaIM = Pr/(HPr+ + Pr). A uniform pKIM of 6.85 (20degreesC) and a deltaHO of 7 kcal/mol are assumed in calculating alphaIM. Intracellular alphaIM is preserved in the tissues studied as body temperature changes. These results indicate that ectotherm acid-base balance, alphastat control, regulates not only extracellular blood proteins, but also intracellular compartment proteins in such a way as to preserve functions dependent upon protein net charge states.", "contents": "Intracellular pH in cold-blooded vertebrates as a function of body temperature. Intracellular pH (pHi) was measured in vivo in tissue of frogs (Rana catesbeiana) and turtles (Pseudemys scripta) using the DMO technique. Animals were permitted 3-8 days to come to a new steady-state body temperature (Tb) which ranged 5-32 degrees C. Least squares regression equation for pHi data are: frog blood, 8.184-0.0206 Tb; frog striated muscle, 7.275-0.0152 Tb; turtle blood, 8.092-0.0207Tb; turtle muscle, 7.421-0.0186 Tb; turtle heart, 7.452-0.0122 Tb; turtle liver, 7.753-0.0233 Tb; turtle esophageal smooth muscle, 7.513-0.0141 Tb. Only turtle cardiac muscle deltapHi/deltaT was significantly different from deltapH/deltaT of blood. Results have been interpreted in terms of protein charge state alterations; in the physiological pH range, histidine residues of proteins are the principal dissociable groups (HPr+ = H+ + Pr) affected by pHi and Tb changes. Constancy of protein charge state can be assessed by monitoring alpha imidazole, alphaIM = Pr/(HPr+ + Pr). A uniform pKIM of 6.85 (20degreesC) and a deltaHO of 7 kcal/mol are assumed in calculating alphaIM. Intracellular alphaIM is preserved in the tissues studied as body temperature changes. These results indicate that ectotherm acid-base balance, alphastat control, regulates not only extracellular blood proteins, but also intracellular compartment proteins in such a way as to preserve functions dependent upon protein net charge states."}
{"id": "PMID:10615", "title": "Model studies of intracellular acid-base temperature responses in ectotherms.", "content": "Measurements of intracellular pH (pHi) in air-breathing ectotherms have only been made in the steady state; these pHi indicate that protein charge state, measured as alpha imidazole (alphaIM), the fractional dissociation of protein histidine imidazole groups, is preserved when ectotherm tissues change temperature in vivo, with related changes in pHi and PCO2. In partial answer to the question of how such tissues are able to avoid disrupting transients to functions sensitive to protein charge states, model studies were carried out to assess the passive intracellular buffer system response to a combined change in body temperature and CO2 partial pressure as occurs in vivo in these species. The cell compartment was modeled as a closed volume of ternary buffer solution, containing protein imidazole (50 mM/1); phosphate (15 mM/1) and CO2-bicarbonate buffer components, permeable only to CO2 and permitted no change in buffer base. Excursions from a steady-state non-equilibrium pHi were computed to a step-change in temperature/PCO2. Computations for frog (Rana catesbeiana) striated muscle show that the calculated pHi response on the basis of estimated composition and concentration of cell buffer components, moves along the curve describing the steady-state temperature relationship. No transient away from steady-state alphaIM and carbon dioxide content need be postulated. Applications to turtle (Pseudemys scripta) striated muscle are also explored. These calculations show that ectotherm cells may be capable of responding without appreciable time for adaptation to intracellular acid-base state changes incurred by sudden alteration of body temperature in vivo, given the observed adjustments of blood PCO2 with temperature.", "contents": "Model studies of intracellular acid-base temperature responses in ectotherms. Measurements of intracellular pH (pHi) in air-breathing ectotherms have only been made in the steady state; these pHi indicate that protein charge state, measured as alpha imidazole (alphaIM), the fractional dissociation of protein histidine imidazole groups, is preserved when ectotherm tissues change temperature in vivo, with related changes in pHi and PCO2. In partial answer to the question of how such tissues are able to avoid disrupting transients to functions sensitive to protein charge states, model studies were carried out to assess the passive intracellular buffer system response to a combined change in body temperature and CO2 partial pressure as occurs in vivo in these species. The cell compartment was modeled as a closed volume of ternary buffer solution, containing protein imidazole (50 mM/1); phosphate (15 mM/1) and CO2-bicarbonate buffer components, permeable only to CO2 and permitted no change in buffer base. Excursions from a steady-state non-equilibrium pHi were computed to a step-change in temperature/PCO2. Computations for frog (Rana catesbeiana) striated muscle show that the calculated pHi response on the basis of estimated composition and concentration of cell buffer components, moves along the curve describing the steady-state temperature relationship. No transient away from steady-state alphaIM and carbon dioxide content need be postulated. Applications to turtle (Pseudemys scripta) striated muscle are also explored. These calculations show that ectotherm cells may be capable of responding without appreciable time for adaptation to intracellular acid-base state changes incurred by sudden alteration of body temperature in vivo, given the observed adjustments of blood PCO2 with temperature."}
{"id": "PMID:10616", "title": "Intracellular buffering of heart and skeletal muscles during the onset of hypercapnia.", "content": "Changes in the total CO2 content of tissues were determined in order to characterize variations in intracellular acid-base parameters during the onset of hypercapnia. Within two minutes after an increasement in the CO2 tension of the inspired air of rats, there were large increases in the intracellular bicarbonate concentrations of both cardiac and skeletal muscles. Greater changes occurred in the heart, and its intracellular pH remained near normal during the first hour of hypercapnia; whereas there was an intracellular acidosis in skeletal muscle. This greater capacity of the heart to buffer excess CO2 has been linked to an increased movement of bicarbonate ions into and/or hydrogen ions out of cardiac cells during hypercapnia (Lai et al., 1973c). Yet, the buffer capacity of the heart was not compromised by metabolic acidosis during which there was a greatly reduced extracellular bicarbonate ion concentration and a greatly increased extracellular hydrogen ion concentration. The intracellular pH of the cardiac ventricle was stable following the imposition of a noncarbonic acid load on normocapnic rats.", "contents": "Intracellular buffering of heart and skeletal muscles during the onset of hypercapnia. Changes in the total CO2 content of tissues were determined in order to characterize variations in intracellular acid-base parameters during the onset of hypercapnia. Within two minutes after an increasement in the CO2 tension of the inspired air of rats, there were large increases in the intracellular bicarbonate concentrations of both cardiac and skeletal muscles. Greater changes occurred in the heart, and its intracellular pH remained near normal during the first hour of hypercapnia; whereas there was an intracellular acidosis in skeletal muscle. This greater capacity of the heart to buffer excess CO2 has been linked to an increased movement of bicarbonate ions into and/or hydrogen ions out of cardiac cells during hypercapnia (Lai et al., 1973c). Yet, the buffer capacity of the heart was not compromised by metabolic acidosis during which there was a greatly reduced extracellular bicarbonate ion concentration and a greatly increased extracellular hydrogen ion concentration. The intracellular pH of the cardiac ventricle was stable following the imposition of a noncarbonic acid load on normocapnic rats."}
{"id": "PMID:10618", "title": "The effect of hepatectomy on the energy state and on acid-base variables of the rat brain.", "content": "The influence of hepatectomy on cerebral energy metabolism was studied in rats in which an end-to-side portacaval anastomosis had been performed one week earlier. The hepatectomy gave rise to an exaggeration of the increase in tissue ammonia content resulting from the shunt. Three hours after the hepatectomy there was a fall in tissue glutamate content but no change in alpha-ketoglutarate. The energy state of the tissue, as evaluated from the concentrations of ATP, ADP, and AMP, was unchanged. There was a significant increase in cerebrospinal fluid pH but no change in intracellular pH.", "contents": "The effect of hepatectomy on the energy state and on acid-base variables of the rat brain. The influence of hepatectomy on cerebral energy metabolism was studied in rats in which an end-to-side portacaval anastomosis had been performed one week earlier. The hepatectomy gave rise to an exaggeration of the increase in tissue ammonia content resulting from the shunt. Three hours after the hepatectomy there was a fall in tissue glutamate content but no change in alpha-ketoglutarate. The energy state of the tissue, as evaluated from the concentrations of ATP, ADP, and AMP, was unchanged. There was a significant increase in cerebrospinal fluid pH but no change in intracellular pH."}
{"id": "PMID:10619", "title": "Microcalorimetric measurements of heat production in human erythrocytes. Heat effect during methylene blue stimulation.", "content": "The metabolic activity in human erythrocytes during stimulation with 10(-4) mol/l methylene blue has been studied by a microcalorimetric method. Simultaneous measurements were performed on cells from the same preparation suspended in different media. Mean values for the ratios between heat effect values were 7.1 +/- 1.0, 7.4 +/- 0.8, and 10.2 +/- 1.7 (+/- S.D.) for cells suspended in plasma, serum, and glucose phosphate buffer, respectively. All heat effect values were corrected to pH 7.40 using the correction factor found in the present work (0.4 % per 0.01 pH unit). The present calorimetric results are in qualitative agreement with previous reports of other investigators concerning the stimulating effect of methylene blue and the influence of pH on the pentose phosphate pathway.", "contents": "Microcalorimetric measurements of heat production in human erythrocytes. Heat effect during methylene blue stimulation. The metabolic activity in human erythrocytes during stimulation with 10(-4) mol/l methylene blue has been studied by a microcalorimetric method. Simultaneous measurements were performed on cells from the same preparation suspended in different media. Mean values for the ratios between heat effect values were 7.1 +/- 1.0, 7.4 +/- 0.8, and 10.2 +/- 1.7 (+/- S.D.) for cells suspended in plasma, serum, and glucose phosphate buffer, respectively. All heat effect values were corrected to pH 7.40 using the correction factor found in the present work (0.4 % per 0.01 pH unit). The present calorimetric results are in qualitative agreement with previous reports of other investigators concerning the stimulating effect of methylene blue and the influence of pH on the pentose phosphate pathway."}
{"id": "PMID:10620", "title": "Effect of the histamine H2-receptor antagonist, cimetidine, on gastric secretion and serum gastrin during insulin infusion in Man.", "content": "Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis.", "contents": "Effect of the histamine H2-receptor antagonist, cimetidine, on gastric secretion and serum gastrin during insulin infusion in Man. Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis."}
{"id": "PMID:10621", "title": "Effect of gastric hypersecretion on the canine duodenum.", "content": "The neutralization of acid introduced into the duodenum has been found to be less intensive in patients with duodenal ulcer than in controls. The present work studied the possibility that chronic gastric hypersecretion injures the duodenal mucosa and thereby influences the neutralization system. Gastric hypersecretion was provoked for 3 weeks in 3 dogs by a daily injection of a gastrin preparation with prolonged effect. After a subcutaneous injection of this preparation given together with a test meal the acidity of both gastric and duodenal contents was found to increase significantly. After the 3 weeks of gastric hypersecretion the pancreatic bicarbonate response to exogenous secretin was unchanged, while the bicarbonate response to duodenal acidification was decreased from 2.03 mEq/30 min to 1.27 mEq/30 min (p less than 0.05), compatible with an impaired secretin release. Also the concentration of lactase, maltase, sucrase, and alkaline phosphatase in mucosal biopsies from the second part of the duodenum was significantly reduced (p less than 0.001). These results indicate that gastric hypersecretion causes mucosal damage in the duodenum and thereby reduces the release of secretin.", "contents": "Effect of gastric hypersecretion on the canine duodenum. The neutralization of acid introduced into the duodenum has been found to be less intensive in patients with duodenal ulcer than in controls. The present work studied the possibility that chronic gastric hypersecretion injures the duodenal mucosa and thereby influences the neutralization system. Gastric hypersecretion was provoked for 3 weeks in 3 dogs by a daily injection of a gastrin preparation with prolonged effect. After a subcutaneous injection of this preparation given together with a test meal the acidity of both gastric and duodenal contents was found to increase significantly. After the 3 weeks of gastric hypersecretion the pancreatic bicarbonate response to exogenous secretin was unchanged, while the bicarbonate response to duodenal acidification was decreased from 2.03 mEq/30 min to 1.27 mEq/30 min (p less than 0.05), compatible with an impaired secretin release. Also the concentration of lactase, maltase, sucrase, and alkaline phosphatase in mucosal biopsies from the second part of the duodenum was significantly reduced (p less than 0.001). These results indicate that gastric hypersecretion causes mucosal damage in the duodenum and thereby reduces the release of secretin."}
{"id": "PMID:10625", "title": "Enkephalin-induced depression of single neurons in brain areas with opiate receptors--antagonism by naloxone.", "content": "Enkephalin, applied microiontophoretically, depressed spontaneous and glutamate-induced firing of single neurons in frontal cortex, caudate nucleus, and periaqueductal gray matter, where enkephalin and high concentrations of opiate receptors are found. Many of the depressions were blocked by the specific narcotic antagonist naloxone. The data are compatible with a neurotransmitter or neuromodulator role for this new brain pentapeptide.", "contents": "Enkephalin-induced depression of single neurons in brain areas with opiate receptors--antagonism by naloxone. Enkephalin, applied microiontophoretically, depressed spontaneous and glutamate-induced firing of single neurons in frontal cortex, caudate nucleus, and periaqueductal gray matter, where enkephalin and high concentrations of opiate receptors are found. Many of the depressions were blocked by the specific narcotic antagonist naloxone. The data are compatible with a neurotransmitter or neuromodulator role for this new brain pentapeptide."}
{"id": "PMID:10622", "title": "Structural studies on des-pentapeptide (B26-30)-insulin. III. State of aggregation, tyrosyl environment, and peptide backbone conformation in solution.", "content": "The three-dimensional structure of des-pentapeptide (B26--30)-insulin (DPI) in solution has been studied by several methods in view of the obvious fact that such knowledge would have much to bear on an understanding of the structure of the receptor-binding site of insulin. (1) The molecular weight of DPI has been studied by the gel filtration method. The results demonstrate that DPI exhibits no self-association behaviour but exists as monomers under the experimental conditions. This enables us to deduce that insulin binds its receptor in the monomeric form; its functional unit is the monomer. (2) The pH difference spectra, denaturation difference spectra, and temperature effect curves have been examined. The results indicate that all three tyrosyl side chains of DPI are unmasked and situated on the surface of the molecule. (3) The UV CD curves of DPI have also been studied. The far UV CD curve of DPI at pH 7.0 is similar to that of insulin, except that the negative value for [iota]220 decreases. This probably demonstrates that the peptide backbone conformation of DPI is very similar to that of insulin, except that it is slightly extended for the former. The near UV CD curve for DPI differs from that for insulin and has an extremum at 266nm as well as a low negative value of [iota]. The assignment of this extremum to Phe and/or -S-S- has been discussed. Taking into consideration the results given in the following papers, it may be concluded that the results of conformation research obtained support our previous working hypothesis that the hydrophobic surface in between the two monomers making up dimeric insulin constitutes a part of the receptor-binding site of insulin.", "contents": "Structural studies on des-pentapeptide (B26-30)-insulin. III. State of aggregation, tyrosyl environment, and peptide backbone conformation in solution. The three-dimensional structure of des-pentapeptide (B26--30)-insulin (DPI) in solution has been studied by several methods in view of the obvious fact that such knowledge would have much to bear on an understanding of the structure of the receptor-binding site of insulin. (1) The molecular weight of DPI has been studied by the gel filtration method. The results demonstrate that DPI exhibits no self-association behaviour but exists as monomers under the experimental conditions. This enables us to deduce that insulin binds its receptor in the monomeric form; its functional unit is the monomer. (2) The pH difference spectra, denaturation difference spectra, and temperature effect curves have been examined. The results indicate that all three tyrosyl side chains of DPI are unmasked and situated on the surface of the molecule. (3) The UV CD curves of DPI have also been studied. The far UV CD curve of DPI at pH 7.0 is similar to that of insulin, except that the negative value for [iota]220 decreases. This probably demonstrates that the peptide backbone conformation of DPI is very similar to that of insulin, except that it is slightly extended for the former. The near UV CD curve for DPI differs from that for insulin and has an extremum at 266nm as well as a low negative value of [iota]. The assignment of this extremum to Phe and/or -S-S- has been discussed. Taking into consideration the results given in the following papers, it may be concluded that the results of conformation research obtained support our previous working hypothesis that the hydrophobic surface in between the two monomers making up dimeric insulin constitutes a part of the receptor-binding site of insulin."}
{"id": "PMID:10626", "title": "beta-Adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex.", "content": "The intraventricular administration of 6-hydroxydopamine, a procedure which destroys noradrenergic nerve terminals in the central nervous system, caused an increase in the density of beta-adrenergic receptors in rat cerebral cortex, without affecting their affinity for isoproterenol. The results suggest that changes in the density of adrenergic receptors are involved in 6-hydroxydopamine-induced supersensitivity at central noradrenergic synapses.", "contents": "beta-Adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex. The intraventricular administration of 6-hydroxydopamine, a procedure which destroys noradrenergic nerve terminals in the central nervous system, caused an increase in the density of beta-adrenergic receptors in rat cerebral cortex, without affecting their affinity for isoproterenol. The results suggest that changes in the density of adrenergic receptors are involved in 6-hydroxydopamine-induced supersensitivity at central noradrenergic synapses."}
{"id": "PMID:10623", "title": "Structural studies on des-pentapeptide (B26-30)-insulin. IV. A preliminary investigation on the hydrophobic region by employing a fluorescence probe, 1-p-toluidinylnaphthalene-8-sulphonate.", "content": "The fluorescnece porperties of 1,8-TNS in relation to the polarity and viscosity of the solvents have been studied and found to be just as useful as those of its positional isomer 2,6-TNS in the capacity of being a fluorescent probe. The properties of the hydrophobic region of insulin, des-pentapeptide (B26-30)- insulin (DPI), bovine plasma albumin, lysozyme, and ovalbumin have been investigated by employing this fluorescent probe. It has been shown that there is a small but definite hydrophobic region in DPI just as in insulin. This suggests that removal of the C-terminal pentapeptide does not impair seriously the hydrophobic structure related to the binding with insulin receptor. However, at physiologic pH, the hydrophobic region of DPI becomes more exposed than that of insulin and its conformation is less stable. As the pH is increased, the local conformation of the DPI molecule probably suffers some distortion, which damages the conformation of the hydrophobic region to a certain extent. In comparison with insulin, the DPI molecule is relatively loose and unstable.", "contents": "Structural studies on des-pentapeptide (B26-30)-insulin. IV. A preliminary investigation on the hydrophobic region by employing a fluorescence probe, 1-p-toluidinylnaphthalene-8-sulphonate. The fluorescnece porperties of 1,8-TNS in relation to the polarity and viscosity of the solvents have been studied and found to be just as useful as those of its positional isomer 2,6-TNS in the capacity of being a fluorescent probe. The properties of the hydrophobic region of insulin, des-pentapeptide (B26-30)- insulin (DPI), bovine plasma albumin, lysozyme, and ovalbumin have been investigated by employing this fluorescent probe. It has been shown that there is a small but definite hydrophobic region in DPI just as in insulin. This suggests that removal of the C-terminal pentapeptide does not impair seriously the hydrophobic structure related to the binding with insulin receptor. However, at physiologic pH, the hydrophobic region of DPI becomes more exposed than that of insulin and its conformation is less stable. As the pH is increased, the local conformation of the DPI molecule probably suffers some distortion, which damages the conformation of the hydrophobic region to a certain extent. In comparison with insulin, the DPI molecule is relatively loose and unstable."}
{"id": "PMID:10624", "title": "Structural studies on des-pentapeptide (B26-30)-insulin. V. High resolution NMR studies.", "content": "Preliminary studies have been made of the 250 MHz nuclear magnetic resonance spectra of both insulin and DPI. Differences have been found between DPI and insulin spectra, which indicate that the splitting off of the B-chain C-terminal pentapeptide from insulin has brought about local changes in the conformation of the protein molecule in solution. It seems that these conformational changes have little effect on the biological activity of the hormone. Many studies have revealed that for insulin molecules in solution, an equilibrium exists between aggregation and dissociation, their state of aggregation bearing a close relationship to the concentration as well as pH of the insulin solution. Changes in the concentration and pH value of DPI solutions do not significantly affect the NMR spectra. But as the concentration and pH of the solution are increased, the methyl regions for valine, leucine, and isoleucine and aromatic regions of the insulin spectra are broadened. All these show that zinc-free DPI molecules probably exist as monomers in solution.", "contents": "Structural studies on des-pentapeptide (B26-30)-insulin. V. High resolution NMR studies. Preliminary studies have been made of the 250 MHz nuclear magnetic resonance spectra of both insulin and DPI. Differences have been found between DPI and insulin spectra, which indicate that the splitting off of the B-chain C-terminal pentapeptide from insulin has brought about local changes in the conformation of the protein molecule in solution. It seems that these conformational changes have little effect on the biological activity of the hormone. Many studies have revealed that for insulin molecules in solution, an equilibrium exists between aggregation and dissociation, their state of aggregation bearing a close relationship to the concentration as well as pH of the insulin solution. Changes in the concentration and pH value of DPI solutions do not significantly affect the NMR spectra. But as the concentration and pH of the solution are increased, the methyl regions for valine, leucine, and isoleucine and aromatic regions of the insulin spectra are broadened. All these show that zinc-free DPI molecules probably exist as monomers in solution."}
{"id": "PMID:10628", "title": "Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster.", "content": "Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction.", "contents": "Ovum aging and pH imbalance as a cause of chromosomal anomalies in the hamster. Using female hamsters mated in estrus, we have produced triploid embryos as manifestations of pregnancy wastage by combining delays of 3 to 4 hours in ferilization with exposure of the animals to hypoxia. Among the triploid embryos only XXX and XXY karotypes occurred, indicating derivation from XX-containing ova. These findings have relevance to human reproduction."}
{"id": "PMID:10629", "title": "Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain.", "content": "The administration of choline in doses previously shown to elevate brain acetylcholine concentrations also increases the activity of tyrosine hydroxylase in rat caudate nuclei. This response can be blocked by atropine, a muscarinic antagonist. These findings indicate that choline-induced increases in acetylcholine concentrations may be associated with parallel changes in the amount of the neurotransmitter released into synapses.", "contents": "Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain. The administration of choline in doses previously shown to elevate brain acetylcholine concentrations also increases the activity of tyrosine hydroxylase in rat caudate nuclei. This response can be blocked by atropine, a muscarinic antagonist. These findings indicate that choline-induced increases in acetylcholine concentrations may be associated with parallel changes in the amount of the neurotransmitter released into synapses."}
{"id": "PMID:10630", "title": "[Capillary sample and blood gas analysis. Technic and validity].", "content": "The authors have developed a technique of sampling and analysis of capillary blood which they describe here. Applied to 34 patients, it gives excellent correlations, both for PO2-PCO2 and pH. The advantages of capillary methods and their disadvantages are discussed.", "contents": "[Capillary sample and blood gas analysis. Technic and validity]. The authors have developed a technique of sampling and analysis of capillary blood which they describe here. Applied to 34 patients, it gives excellent correlations, both for PO2-PCO2 and pH. The advantages of capillary methods and their disadvantages are discussed."}
{"id": "PMID:10632", "title": "Skin changes in graft-vs-host disease.", "content": "In this review of the clinical and histopathologic manifestations of the graft-vs-host reaction, the characteristic changes in the skin are given particular emphasis, since they are among the earliest and most obvious signs of this syndrome. The acute and chronic forms of graft-vs-host disease are distinguished, with notation of their different dermatologic presentations. The distinctive histopathologic and immunopathologic findings of the graft-vs-host reaction in the skin are presented. Finally, the possible pathogenetic mechanisms which produce the clinical picuture of graft-vs-host disease are discussed. Both T cells and B cells apparently are involved, as are macrophages, but what is primary and what is secondary in the reaction remains to be delineated, as do the respective contributions of donor and host cells.", "contents": "Skin changes in graft-vs-host disease. In this review of the clinical and histopathologic manifestations of the graft-vs-host reaction, the characteristic changes in the skin are given particular emphasis, since they are among the earliest and most obvious signs of this syndrome. The acute and chronic forms of graft-vs-host disease are distinguished, with notation of their different dermatologic presentations. The distinctive histopathologic and immunopathologic findings of the graft-vs-host reaction in the skin are presented. Finally, the possible pathogenetic mechanisms which produce the clinical picuture of graft-vs-host disease are discussed. Both T cells and B cells apparently are involved, as are macrophages, but what is primary and what is secondary in the reaction remains to be delineated, as do the respective contributions of donor and host cells."}
{"id": "PMID:10633", "title": "The introduction of SI units and the standardisation of laboratory reports: recommendations of the South African Association of Clinical Biochemists.", "content": "The change of SI units in laboratory reporting is occurring in South Africa. To assist this process and to ensure uniformity among laboratories, the Recommendations of the South African Association of Clinical Biochemists are presented. Controversial points are discussed and subunits selected. A standardised format of laboratory reports is suggested.", "contents": "The introduction of SI units and the standardisation of laboratory reports: recommendations of the South African Association of Clinical Biochemists. The change of SI units in laboratory reporting is occurring in South Africa. To assist this process and to ensure uniformity among laboratories, the Recommendations of the South African Association of Clinical Biochemists are presented. Controversial points are discussed and subunits selected. A standardised format of laboratory reports is suggested."}
{"id": "PMID:10634", "title": "The effect of microaggregates in stored blood on canine pulmonary vascular resistance.", "content": "Microaggregates have been implicated as a contributory cause of respiratory distress syndrome. Blood flow and resistance changes are compared between the right and left lungs following the selective administration of stored autologous heparinized blood into the left pulmonary artery. Eight dogs were bled 1,160 +/- 47 c.c. over 3 days. Following storage for 5 days the volume, number and size of microaggregates were measured by multichannel particle size analyzer and compared to 14-day-old human blood. Distribution of blood flow and resistance were calculated from data derived from injection of radioactively tagged microspheres into the right atrium and determination of cardiac output and pulmonary artery and wedge pressures. These measurements were made during a control period, following resuscitation from a 2 hour hemorrhagic shock period with the stored blood and 3 hours after resuscitation. Despite the administration of stored blood with massive amounts of microaggregates into the left pulmonary artery, the distribution of blood flow immediately and 3 hours following resuscitation was the same as in the control period. The pulmonary vascular resistance increased across both lungs but the increase was the same on the left as the right. These data suggest that microaggregates may not be important in the development of the respiratory distress syndrome.", "contents": "The effect of microaggregates in stored blood on canine pulmonary vascular resistance. Microaggregates have been implicated as a contributory cause of respiratory distress syndrome. Blood flow and resistance changes are compared between the right and left lungs following the selective administration of stored autologous heparinized blood into the left pulmonary artery. Eight dogs were bled 1,160 +/- 47 c.c. over 3 days. Following storage for 5 days the volume, number and size of microaggregates were measured by multichannel particle size analyzer and compared to 14-day-old human blood. Distribution of blood flow and resistance were calculated from data derived from injection of radioactively tagged microspheres into the right atrium and determination of cardiac output and pulmonary artery and wedge pressures. These measurements were made during a control period, following resuscitation from a 2 hour hemorrhagic shock period with the stored blood and 3 hours after resuscitation. Despite the administration of stored blood with massive amounts of microaggregates into the left pulmonary artery, the distribution of blood flow immediately and 3 hours following resuscitation was the same as in the control period. The pulmonary vascular resistance increased across both lungs but the increase was the same on the left as the right. These data suggest that microaggregates may not be important in the development of the respiratory distress syndrome."}
{"id": "PMID:10636", "title": "Purification and properties of human factor IXa.", "content": "Human factor IXa was purified 5,000-fold from serum by ion exchange chromatography. The preparation was free from other clotting factors. Both pH sensitivity and heat stability of purified factor IXa appeared to be different from those of factor IX in the plasma. The molecular weight of human factor IXa is 80,000 as estimated from gel-filtration experiments. Modification of seryl or histidyl side chains abolished the activity of factor IXa.", "contents": "Purification and properties of human factor IXa. Human factor IXa was purified 5,000-fold from serum by ion exchange chromatography. The preparation was free from other clotting factors. Both pH sensitivity and heat stability of purified factor IXa appeared to be different from those of factor IX in the plasma. The molecular weight of human factor IXa is 80,000 as estimated from gel-filtration experiments. Modification of seryl or histidyl side chains abolished the activity of factor IXa."}
{"id": "PMID:10637", "title": "Reactivity of fibrinogen crosslinking sites in the absence of thrombin.", "content": "The reactivity of fibrinogen crosslinking sites with thrombin-free, preactivated factor XIII (F. XIIIa) was investigated under different conditions such as increased ionic strength, presence of urea, protamine sulfate (PS) or of varying concentrations of monodansylcadaverine (MDC). Crosslinking and incorporation of MDC into fibrinogen or fibrin gamma- and alpha-chains were evaluated by SDS-polyacrylamide gel electrophoresis. According to our results, rates of crosslinking of, and of MDC incorporation into, both gamma- and alpha-chains of fibrinogen were low under physiological conditions; they were not significantly influenced by the presence of either 1.0 M NaCl or 1.0 M urea. In contrast, 0.01% PS precipitated fibrinogen, and, simultaneously, significantly increased the rates of crosslinking and of MDC incorporation into both gamma- and alpha-chains. MDC, at concentrations above approximately 6 mM, also precipitated fibrinogen, and, up to a concentration of about 9 mM, markedly enhanced the reactivity of acceptor crosslinking sites. Our results suggest that solubility of fibrinogen and the conformational arrangement of its subunit chains are closely interdependent; the reactivity of crosslinking sites with F. XIIIa seems to be a function of this conformational state.", "contents": "Reactivity of fibrinogen crosslinking sites in the absence of thrombin. The reactivity of fibrinogen crosslinking sites with thrombin-free, preactivated factor XIII (F. XIIIa) was investigated under different conditions such as increased ionic strength, presence of urea, protamine sulfate (PS) or of varying concentrations of monodansylcadaverine (MDC). Crosslinking and incorporation of MDC into fibrinogen or fibrin gamma- and alpha-chains were evaluated by SDS-polyacrylamide gel electrophoresis. According to our results, rates of crosslinking of, and of MDC incorporation into, both gamma- and alpha-chains of fibrinogen were low under physiological conditions; they were not significantly influenced by the presence of either 1.0 M NaCl or 1.0 M urea. In contrast, 0.01% PS precipitated fibrinogen, and, simultaneously, significantly increased the rates of crosslinking and of MDC incorporation into both gamma- and alpha-chains. MDC, at concentrations above approximately 6 mM, also precipitated fibrinogen, and, up to a concentration of about 9 mM, markedly enhanced the reactivity of acceptor crosslinking sites. Our results suggest that solubility of fibrinogen and the conformational arrangement of its subunit chains are closely interdependent; the reactivity of crosslinking sites with F. XIIIa seems to be a function of this conformational state."}
{"id": "PMID:10638", "title": "Aggregation of platelets and inert particles induced by thrombin.", "content": "Thrombin-induced platelet aggregation and release were investigated in washed platelet suspensions and in suspensions of inert particles in order to evaluate the role of fibrinogen-fibrin transformation in aggregometer tracings. Thrombin (0.25-2.0 U/ml) produced two waves of light transmission increase (LTI) in both platelet and inert particle suspensions containing fibrinogen, and concomittantly aggregates were observed under phase microscopy. Without fibrinogen, thrombin induced rapid release of platelet ADP but failed to cause second wave of LTI. The kinetics of LTI in platelet and inert particle systems were related to both thrombin and fibrinogen concentrations. A rapid second wave of LTI could be produced by direct interaction of thrombin-treated platelets or inert particles with polymerizing fibrin, and was inhibited by sodium sulfite and low pH of 5.1 which prevent fibrin monomer polymerization. No fibrin strands were noted in platelet aggregates fixed at the completion of the second wave of LTI. Apyrase and PGE1 inhibited the rate of first but not that of second wave LTI. The results suggest that the release of platelet ADP induced by thrombin primarily affects the first phase aggregation, and the second phase may result from interaction of thrombin-exposed platelets and polymerizing fibrin. Thus, the blood coagulation mechanism may be directly involved in platelet aggregation.", "contents": "Aggregation of platelets and inert particles induced by thrombin. Thrombin-induced platelet aggregation and release were investigated in washed platelet suspensions and in suspensions of inert particles in order to evaluate the role of fibrinogen-fibrin transformation in aggregometer tracings. Thrombin (0.25-2.0 U/ml) produced two waves of light transmission increase (LTI) in both platelet and inert particle suspensions containing fibrinogen, and concomittantly aggregates were observed under phase microscopy. Without fibrinogen, thrombin induced rapid release of platelet ADP but failed to cause second wave of LTI. The kinetics of LTI in platelet and inert particle systems were related to both thrombin and fibrinogen concentrations. A rapid second wave of LTI could be produced by direct interaction of thrombin-treated platelets or inert particles with polymerizing fibrin, and was inhibited by sodium sulfite and low pH of 5.1 which prevent fibrin monomer polymerization. No fibrin strands were noted in platelet aggregates fixed at the completion of the second wave of LTI. Apyrase and PGE1 inhibited the rate of first but not that of second wave LTI. The results suggest that the release of platelet ADP induced by thrombin primarily affects the first phase aggregation, and the second phase may result from interaction of thrombin-exposed platelets and polymerizing fibrin. Thus, the blood coagulation mechanism may be directly involved in platelet aggregation."}
{"id": "PMID:10643", "title": "Human immunity to rat antigens. II. Immune responses in dialysis patients.", "content": "The immune status of 35 patients with renal failure was studied shortly after they had commenced treatment by chronic haemodialysis to see if a group with poor immunological responses could be identified. Of 27 patients who were unimmunised to start with, only two developed lymphocytoxic antibodies after a year of treatment. The routine immunological tests that were carried out on these patients failed to predict which of them would develop antibodies, and the values that were obtained for the group of cytotoxic negative patients were no different from those obtained for the two patients who became immunised and six others who had previously rejected a kidney transplant. By using a new test that measured cellular immunity to rat antigens, eight patients could be identified as \"poor responders.\" These individuals had in addition failed to develop cytotoxic antibodies during dialysis, had serum IgG levels that were significantly lower than normal, and were uniformly unresponsive to purified protein derivative. This group of patients might be a favoruable one to transplant.", "contents": "Human immunity to rat antigens. II. Immune responses in dialysis patients. The immune status of 35 patients with renal failure was studied shortly after they had commenced treatment by chronic haemodialysis to see if a group with poor immunological responses could be identified. Of 27 patients who were unimmunised to start with, only two developed lymphocytoxic antibodies after a year of treatment. The routine immunological tests that were carried out on these patients failed to predict which of them would develop antibodies, and the values that were obtained for the group of cytotoxic negative patients were no different from those obtained for the two patients who became immunised and six others who had previously rejected a kidney transplant. By using a new test that measured cellular immunity to rat antigens, eight patients could be identified as \"poor responders.\" These individuals had in addition failed to develop cytotoxic antibodies during dialysis, had serum IgG levels that were significantly lower than normal, and were uniformly unresponsive to purified protein derivative. This group of patients might be a favoruable one to transplant."}
{"id": "PMID:10644", "title": "Studies on a systemic xenogeneic graft-versus-host reaction model in newborn mice.", "content": "A xenogeneic graft-versus-host reaction model is described, evoked in neonatal mice by injection of rat spleen cells, and registered as splenomegaly at day 7. The following arguments are given as support for the idea that the reaction is indeed a graft-versus-host reaction: only living rat cells can give the reaction; rat cells treated with antilymphocyte serum cannot do so. The reaction is of almost the same strength in mice which have thymus dysplasia and are probably incapable of mounting a host-versus-graft reaction. Pretreatment of the grafted cells with mitomycin C, which abolishes the cells' capacity for DNA synthesis and proliferation, also eliminates their capacity to cause splenomegaly. This is probably because the grafted cell clone, reactive to mouse antigens, is small and has to be expended in order to be effective. Dividing rat cells have been demonstrated by chromosome studies in the enlarged mouse spleens 2--6 days after grafting.", "contents": "Studies on a systemic xenogeneic graft-versus-host reaction model in newborn mice. A xenogeneic graft-versus-host reaction model is described, evoked in neonatal mice by injection of rat spleen cells, and registered as splenomegaly at day 7. The following arguments are given as support for the idea that the reaction is indeed a graft-versus-host reaction: only living rat cells can give the reaction; rat cells treated with antilymphocyte serum cannot do so. The reaction is of almost the same strength in mice which have thymus dysplasia and are probably incapable of mounting a host-versus-graft reaction. Pretreatment of the grafted cells with mitomycin C, which abolishes the cells' capacity for DNA synthesis and proliferation, also eliminates their capacity to cause splenomegaly. This is probably because the grafted cell clone, reactive to mouse antigens, is small and has to be expended in order to be effective. Dividing rat cells have been demonstrated by chromosome studies in the enlarged mouse spleens 2--6 days after grafting."}
{"id": "PMID:10648", "title": "Correlation of graft-versus-host mortality and positive CML assay in the mouse.", "content": "GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo.", "contents": "Correlation of graft-versus-host mortality and positive CML assay in the mouse. GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo."}
{"id": "PMID:10655", "title": "Properties of 3',5'-cyclic-AMP phosphodiesterase from Paragonimus africanus metacercariae.", "content": "3',5'-Cyclic-AMP 5'-nucleotidohydrolase (cAMP phosphodiesterase, EC 3.1.4.17) was partial purified from metacercariae of Paragonimus africanus. The enzyme activity absolutely depends on Mg2 or Mn2+. The pH-optimum of the cAMP phosphidiesterase was found at pH 8.0. The Michaelis constant for cAMP was determined to be 5 X 10(-6) M. Papaverine deoxyadenosine, theophylline and adenosine were found to be competitive inhibitors of the enzyme activity. The inhibitor constants were calculated to be 13 X 10(-6)M, 25 X 10(-5)M, and 35 X 10(-5)M, and 85 X 10(-5)M,respectively. The molecular weight of the cAMP phosphodiesterase was estimated to be about 40 000 by gel filtration.", "contents": "Properties of 3',5'-cyclic-AMP phosphodiesterase from Paragonimus africanus metacercariae. 3',5'-Cyclic-AMP 5'-nucleotidohydrolase (cAMP phosphodiesterase, EC 3.1.4.17) was partial purified from metacercariae of Paragonimus africanus. The enzyme activity absolutely depends on Mg2 or Mn2+. The pH-optimum of the cAMP phosphidiesterase was found at pH 8.0. The Michaelis constant for cAMP was determined to be 5 X 10(-6) M. Papaverine deoxyadenosine, theophylline and adenosine were found to be competitive inhibitors of the enzyme activity. The inhibitor constants were calculated to be 13 X 10(-6)M, 25 X 10(-5)M, and 35 X 10(-5)M, and 85 X 10(-5)M,respectively. The molecular weight of the cAMP phosphodiesterase was estimated to be about 40 000 by gel filtration."}
{"id": "PMID:10657", "title": "[Hydrogen ion activity in the cell].", "content": "Literature data and results of our experiments evidence for a heterogenous hydrogen distribution in cells. Intracellular pH should be regarded as a mean activity of hydrogen ions which is the sum of activities in different phases of a cell. Intracellular pH value does not depend on the transmembrane action potential difference, and is resistant to respiratory and metabolic disorders of acid-base equilibrium in the body. It also slightly changes with changing the electrolyte composition and pH of the medium and is not influenced by metabolic inhibitors. A low hydrogen activity in the cell has a certain functional significance. The pH stability is ensured by a number of regulatory mechanism: the buffer properties of the protoplasm itself, and the active hydrogen transport into the medium. Hydrogen released from cells is supposed to be connected with functioning of a specific respiratory chain of superficial protoplasmic membranes.", "contents": "[Hydrogen ion activity in the cell]. Literature data and results of our experiments evidence for a heterogenous hydrogen distribution in cells. Intracellular pH should be regarded as a mean activity of hydrogen ions which is the sum of activities in different phases of a cell. Intracellular pH value does not depend on the transmembrane action potential difference, and is resistant to respiratory and metabolic disorders of acid-base equilibrium in the body. It also slightly changes with changing the electrolyte composition and pH of the medium and is not influenced by metabolic inhibitors. A low hydrogen activity in the cell has a certain functional significance. The pH stability is ensured by a number of regulatory mechanism: the buffer properties of the protoplasm itself, and the active hydrogen transport into the medium. Hydrogen released from cells is supposed to be connected with functioning of a specific respiratory chain of superficial protoplasmic membranes."}
{"id": "PMID:10664", "title": "In situ dissolution of ureteral calculus.", "content": "An obstructing uric acid calculus was successfully managed by dissolution in situ. The methods used are described in detail. Perhaps not applicable in all cases, the ease of the procedure makes it worth considering especially in patients at high risk for open operative intervention.", "contents": "In situ dissolution of ureteral calculus. An obstructing uric acid calculus was successfully managed by dissolution in situ. The methods used are described in detail. Perhaps not applicable in all cases, the ease of the procedure makes it worth considering especially in patients at high risk for open operative intervention."}
{"id": "PMID:10665", "title": "[Activity and variability of aminopeptidases and gamma-glutamyl transpeptidase of the cutaneous mucous membrane in the cow's rumen].", "content": "The authors studied the activity, chromatographic and electrophoretic distribution of leucylarylamidase, cystinamino peptidase, and gamma-glutamyl transpeptidase of the cytoplasmatic fraction of cow's rumen mucous membrane homogenate. The results of comparative analysis draw attention to the existence of a certain number of the molecular forms of the enzymes studied, to the activation of leucylarylamidase by Co2+, cystinamino peptidase by Co2+ and Ca2+. The possible functions of the amino peptidases and transpeptidase of glutamic acid in the metabolism of nitrogen compounds of the type of peptides, amino acids, and their amides, are discussed in the study.", "contents": "[Activity and variability of aminopeptidases and gamma-glutamyl transpeptidase of the cutaneous mucous membrane in the cow's rumen]. The authors studied the activity, chromatographic and electrophoretic distribution of leucylarylamidase, cystinamino peptidase, and gamma-glutamyl transpeptidase of the cytoplasmatic fraction of cow's rumen mucous membrane homogenate. The results of comparative analysis draw attention to the existence of a certain number of the molecular forms of the enzymes studied, to the activation of leucylarylamidase by Co2+, cystinamino peptidase by Co2+ and Ca2+. The possible functions of the amino peptidases and transpeptidase of glutamic acid in the metabolism of nitrogen compounds of the type of peptides, amino acids, and their amides, are discussed in the study."}
{"id": "PMID:10666", "title": "[Effectiveness of various barbiturates in chickens of different ages].", "content": "Phenobarbital, allobarbital, and pentobarbital in the doses of 40 and 80 mg per 1 kg body mass were applied intramuscularly to groups of the cockerels of the WL breed at the age of two days, one, two, and six weeks (each group had ten birds) and to eight-week-old WL cockerels in groups of five birds. The methods of clinical observation and repeated determination of the response of the animals to sonic stimuli and contact stimuli, and the evaluation of the quality of some reflexes (particularly the spontaneous position of the body and the correction of the lateral position) were used for the study of suppression evoked by the applied barbiturates. Sleep occurred first after the application of pentobarbital (sooner in younger age groups). The latest beginning of sleep was observed after phenobarbital; in the latter case, sleep was hard to evaluate because it was not very deep. The time of sleep had the longest duration after allobarbital (only in the eight-week-old sleep was longer after pentobarbital), and the shortest after phenobarbital; there were also differences in the duration of sleep between the age groups of birds. The pentobarbital dose of 80 mg kg-1 of body mass killed birds in the three youngest age groups )in the two-day-old it killed nine of ten birds, in the one-week-old eight of ten birds, and in the two-week-old two of ten birds). The differences in the effectiveness of the applied barbiturates in two doses per unit of body mass were related to the age of the animals, even in the cases of the shortest age intervals between individual groups. Very high interspecies differences ensue from a comparison with the doses of these barbiturates usually applied to man.", "contents": "[Effectiveness of various barbiturates in chickens of different ages]. Phenobarbital, allobarbital, and pentobarbital in the doses of 40 and 80 mg per 1 kg body mass were applied intramuscularly to groups of the cockerels of the WL breed at the age of two days, one, two, and six weeks (each group had ten birds) and to eight-week-old WL cockerels in groups of five birds. The methods of clinical observation and repeated determination of the response of the animals to sonic stimuli and contact stimuli, and the evaluation of the quality of some reflexes (particularly the spontaneous position of the body and the correction of the lateral position) were used for the study of suppression evoked by the applied barbiturates. Sleep occurred first after the application of pentobarbital (sooner in younger age groups). The latest beginning of sleep was observed after phenobarbital; in the latter case, sleep was hard to evaluate because it was not very deep. The time of sleep had the longest duration after allobarbital (only in the eight-week-old sleep was longer after pentobarbital), and the shortest after phenobarbital; there were also differences in the duration of sleep between the age groups of birds. The pentobarbital dose of 80 mg kg-1 of body mass killed birds in the three youngest age groups )in the two-day-old it killed nine of ten birds, in the one-week-old eight of ten birds, and in the two-week-old two of ten birds). The differences in the effectiveness of the applied barbiturates in two doses per unit of body mass were related to the age of the animals, even in the cases of the shortest age intervals between individual groups. Very high interspecies differences ensue from a comparison with the doses of these barbiturates usually applied to man."}
{"id": "PMID:10684", "title": "Microsomal styrene mono-oxygenase and styrene epoxide hydrase activities in rats.", "content": "1. Styrene epoxide formation and styrene epoxide hydration have been studied in liver, lung, kidney, heart, spleen and brain of female and male rats. 2. Styrene epoxide formation is NADPH-dependent although it is enhanced when NADH is added together with NADP. This enzymic activity is inhibited by metyrapone and SKF 525-A but not by the effective inhibitors of epoxide hydrase, 1,2-epoxy-3,3,3-trichloropropene and cyclohexene oxide. 3. Known inducers of liver microsomal mono-oxygenases show a different activity on the two enzymes. Phenobarbital increases both formation and hydration of styrene epoxide; and carbamazepine increase the hydration but not the formation of styrene epoxide; a steroid contraceptive combination (lynestrenol+ mestranol) increases styrene epoxide formation while it inhibits epoxide hydrase; 3-methylcholanthrene does not affect either of the activities.", "contents": "Microsomal styrene mono-oxygenase and styrene epoxide hydrase activities in rats. 1. Styrene epoxide formation and styrene epoxide hydration have been studied in liver, lung, kidney, heart, spleen and brain of female and male rats. 2. Styrene epoxide formation is NADPH-dependent although it is enhanced when NADH is added together with NADP. This enzymic activity is inhibited by metyrapone and SKF 525-A but not by the effective inhibitors of epoxide hydrase, 1,2-epoxy-3,3,3-trichloropropene and cyclohexene oxide. 3. Known inducers of liver microsomal mono-oxygenases show a different activity on the two enzymes. Phenobarbital increases both formation and hydration of styrene epoxide; and carbamazepine increase the hydration but not the formation of styrene epoxide; a steroid contraceptive combination (lynestrenol+ mestranol) increases styrene epoxide formation while it inhibits epoxide hydrase; 3-methylcholanthrene does not affect either of the activities."}
{"id": "PMID:10685", "title": "[Absorption, distribution and excretion of (quinuclidinyl-3 methyl)-10-phenothiazine (LM 209), a new antihistamine].", "content": "1. The absorption, distribution and elimination of 10-(3-quinuclidinylmethyl)-phenothiazine (LM 209) were studied in the rat and dog after oral or intravenous administration of the 35S-labelled molecule. 2. Determinations of radioactivity in the rat and dog confirmed absorption and showed that the blood levels increase in proportion to the dose but remain very low compared with tissue concentrations. These were highest in the liver and lung and persisted at high level for more than 6 h after dosage. 3. Excretion of radioactivity was by the urinary and faecal routes. The high level of radioactivity in faeces resulted mainly from biliary excretion which was accompanied by much entero-hepatic circulation. 4. The prolonged retention of LM 209, due to binding to blood and tissue proteins and to entero-hepatic circulation, did not lead to noticeable accumulation of the drug after repeated doses. 5. The difference in the intracellular distribution of LM 209 and phenothiazine shows the importance of the quinuclidine N-subsitution on the phenothiazine ring, and results in a greater affinity to sub-cellular particulate fractions (nuclei, mitochondria, microsomes).", "contents": "[Absorption, distribution and excretion of (quinuclidinyl-3 methyl)-10-phenothiazine (LM 209), a new antihistamine]. 1. The absorption, distribution and elimination of 10-(3-quinuclidinylmethyl)-phenothiazine (LM 209) were studied in the rat and dog after oral or intravenous administration of the 35S-labelled molecule. 2. Determinations of radioactivity in the rat and dog confirmed absorption and showed that the blood levels increase in proportion to the dose but remain very low compared with tissue concentrations. These were highest in the liver and lung and persisted at high level for more than 6 h after dosage. 3. Excretion of radioactivity was by the urinary and faecal routes. The high level of radioactivity in faeces resulted mainly from biliary excretion which was accompanied by much entero-hepatic circulation. 4. The prolonged retention of LM 209, due to binding to blood and tissue proteins and to entero-hepatic circulation, did not lead to noticeable accumulation of the drug after repeated doses. 5. The difference in the intracellular distribution of LM 209 and phenothiazine shows the importance of the quinuclidine N-subsitution on the phenothiazine ring, and results in a greater affinity to sub-cellular particulate fractions (nuclei, mitochondria, microsomes)."}
{"id": "PMID:10686", "title": "Metronidazole (Flagyl): degradation by the intestinal flora.", "content": "1. Metronidazole (Flagyl) is reduced exponentially by the contents of the rat caecum in the absence of oxygen. The rate of removal is highest at pH 7 and 37 degrees. 2. Reduction of the drug is inhibited by boiling of the caecal contents, CHCl3, Cu2+, Ag+, azodicarboxylic acid bis-dimethylamide, p-chloromercuric benzoate, N-ethylmaleimide and 4,4,4-trifluoro-1,2-thienyl-1,3-butanedione. Nitrate, ethanol (3%), CO, phenol and amytal did not affect the rate of reduction. 3. It is concluded that iron-sulphur systems are involved in degradation of the drug.", "contents": "Metronidazole (Flagyl): degradation by the intestinal flora. 1. Metronidazole (Flagyl) is reduced exponentially by the contents of the rat caecum in the absence of oxygen. The rate of removal is highest at pH 7 and 37 degrees. 2. Reduction of the drug is inhibited by boiling of the caecal contents, CHCl3, Cu2+, Ag+, azodicarboxylic acid bis-dimethylamide, p-chloromercuric benzoate, N-ethylmaleimide and 4,4,4-trifluoro-1,2-thienyl-1,3-butanedione. Nitrate, ethanol (3%), CO, phenol and amytal did not affect the rate of reduction. 3. It is concluded that iron-sulphur systems are involved in degradation of the drug."}
{"id": "PMID:10687", "title": "Mechanism of 2-naphthylamine oxidation catalysed by pig liver microsomes.", "content": "1. In pig liver microsomes 2-naphthylamine-dependent NADPH oxidation, oxygen reduction, and hydroxylamine formation are linear with time for several minutes. A sharp increase in NADPH oxidation and oxygen uptake then coincides with an abrupt loss of hydroxylamine from the medium. 2. The initial rate of 2-naphthylamine N-oxidation correlates with the microsomal concentration of mixed-function amine oxidase and the extent of linear accumulation of hydroxylamine is dependent on microsomal NADPH-cytochrome c reductase activity and concentration of lipid (microsomes). 3. Antisera to NADPH-cytochrome c reductase markedly decreased hydroxylamine accumulation during incubation but had no effect on the rate of 2-naphthylamine N-oxidation. 4. A system duplicating all of the kinetic properties of the microsomal 2-naphthylamine oxidase was constructed with two purified flavoproteins, (mixed-function amine oxidase and NADPH-cytochrome c reductase) and a lipid phase (erythrocyte ghosts or synthetic lecithin liposomes). 5. By independently varying the concentrations of each component in the reconstituted system, the contribution of each to the observed kinetics was defined. 6. In addition to the initial N-oxidation of 2-naphthylamine, at least six other reactions contribute to the kinetic patterns of 2-naphthylamine oxidation catalysed by the reconstituted system.", "contents": "Mechanism of 2-naphthylamine oxidation catalysed by pig liver microsomes. 1. In pig liver microsomes 2-naphthylamine-dependent NADPH oxidation, oxygen reduction, and hydroxylamine formation are linear with time for several minutes. A sharp increase in NADPH oxidation and oxygen uptake then coincides with an abrupt loss of hydroxylamine from the medium. 2. The initial rate of 2-naphthylamine N-oxidation correlates with the microsomal concentration of mixed-function amine oxidase and the extent of linear accumulation of hydroxylamine is dependent on microsomal NADPH-cytochrome c reductase activity and concentration of lipid (microsomes). 3. Antisera to NADPH-cytochrome c reductase markedly decreased hydroxylamine accumulation during incubation but had no effect on the rate of 2-naphthylamine N-oxidation. 4. A system duplicating all of the kinetic properties of the microsomal 2-naphthylamine oxidase was constructed with two purified flavoproteins, (mixed-function amine oxidase and NADPH-cytochrome c reductase) and a lipid phase (erythrocyte ghosts or synthetic lecithin liposomes). 5. By independently varying the concentrations of each component in the reconstituted system, the contribution of each to the observed kinetics was defined. 6. In addition to the initial N-oxidation of 2-naphthylamine, at least six other reactions contribute to the kinetic patterns of 2-naphthylamine oxidation catalysed by the reconstituted system."}
{"id": "PMID:10688", "title": "Production physiology and properties of a novel fungal fibrinolytic enzyme.", "content": "A potent extracellular fibrinolytic enzyme was obtained from cultures of the imperfect fungus Fusarium semitectum under certain growth conditions. Nitrate addition to cultures increased enzyme production. The enzyme showed a versatile proteolytic activity against several protein substrates including casein, gelatin, haemoglobin, bovine serum albumin, and fibrin from both buffalo and human sources. Optimal fibrinolysis occurred at pH values around 7.0. The fibrinolytic activity exhibited marked heat stability in enzyme samples heated at 60 degrees C, and retained more than 40% of its activity in samples heated to 100 degrees C for 10 min. Fibrinolysis proceeded optimally in the temperature range between 50--60 degrees C. Copper ions significantly activated the enzyme. Other biochemical properties are also reported.", "contents": "Production physiology and properties of a novel fungal fibrinolytic enzyme. A potent extracellular fibrinolytic enzyme was obtained from cultures of the imperfect fungus Fusarium semitectum under certain growth conditions. Nitrate addition to cultures increased enzyme production. The enzyme showed a versatile proteolytic activity against several protein substrates including casein, gelatin, haemoglobin, bovine serum albumin, and fibrin from both buffalo and human sources. Optimal fibrinolysis occurred at pH values around 7.0. The fibrinolytic activity exhibited marked heat stability in enzyme samples heated at 60 degrees C, and retained more than 40% of its activity in samples heated to 100 degrees C for 10 min. Fibrinolysis proceeded optimally in the temperature range between 50--60 degrees C. Copper ions significantly activated the enzyme. Other biochemical properties are also reported."}
{"id": "PMID:10689", "title": "[Cleavage of alpha-L-arabinofuranoside, beta-D-glucopyranoside and beta-cellobioside of 4-nitrophenol by enzymes of various fungi - a contribution to increase the selectivity of tumor therapy].", "content": "To carry out long-term experiments as part of a therapy concept of malignant tumours using inactive transport forms of cancerostatic substances and their specific cleavage in the acidic pH region of the tumours by application of extraneous enzymes, we require enzymes with similar catalytic and pharmacokinetic properties which differ from each other in immunological respect. In the search for such enzymes, the alpha-L-arabinofuranosidases from 12 different fungi, among them 9 basidiomycetes, were studied. The enzymes mentioned were demonstrable in all fungi. Optimum pH values ranged between 2.5 and 5.5. The Km values for the cleavage of alpha-L-arabinofuranoside were, in most cases, 0.5 to 1.8 moles-liter-1-10(-3). With regard to pH dependence, the alpha-L-arabinofuranosidases of most of the fungi investigated proved adequate for the long-term trials envisaged. 4-nitrophenyl-beta-D-glucopyranoside and -beta-cellobioside were also cleaved by enzyme preparations of all the 11 fungi investigated. The beta-D-glucopyranosidases showed a less favourable pH dependence than the alpha-L-arabinofuranosidases. The cleavage of 4-nitrophenyl-beta-cellobioside, on the contrary, showed mostly a comparatively favourable pH dependence. On the basis of the coinciding optimal pH values and the occurrence of 4-nitrophenyl-beta-D-glucopyranoside as an intermediate product in the cleavage of the corresponding cellobioside, we assume that both substrates are cleaved by beta-glucosidase. Because the occurrence of the glucoside during the cleavage of cellobioside is undesirable for the therapeutic trial, a method is proposed for selection of an appropriate cellobioside splitting enzyme basing on the present studies and the relevant literature.", "contents": "[Cleavage of alpha-L-arabinofuranoside, beta-D-glucopyranoside and beta-cellobioside of 4-nitrophenol by enzymes of various fungi - a contribution to increase the selectivity of tumor therapy]. To carry out long-term experiments as part of a therapy concept of malignant tumours using inactive transport forms of cancerostatic substances and their specific cleavage in the acidic pH region of the tumours by application of extraneous enzymes, we require enzymes with similar catalytic and pharmacokinetic properties which differ from each other in immunological respect. In the search for such enzymes, the alpha-L-arabinofuranosidases from 12 different fungi, among them 9 basidiomycetes, were studied. The enzymes mentioned were demonstrable in all fungi. Optimum pH values ranged between 2.5 and 5.5. The Km values for the cleavage of alpha-L-arabinofuranoside were, in most cases, 0.5 to 1.8 moles-liter-1-10(-3). With regard to pH dependence, the alpha-L-arabinofuranosidases of most of the fungi investigated proved adequate for the long-term trials envisaged. 4-nitrophenyl-beta-D-glucopyranoside and -beta-cellobioside were also cleaved by enzyme preparations of all the 11 fungi investigated. The beta-D-glucopyranosidases showed a less favourable pH dependence than the alpha-L-arabinofuranosidases. The cleavage of 4-nitrophenyl-beta-cellobioside, on the contrary, showed mostly a comparatively favourable pH dependence. On the basis of the coinciding optimal pH values and the occurrence of 4-nitrophenyl-beta-D-glucopyranoside as an intermediate product in the cleavage of the corresponding cellobioside, we assume that both substrates are cleaved by beta-glucosidase. Because the occurrence of the glucoside during the cleavage of cellobioside is undesirable for the therapeutic trial, a method is proposed for selection of an appropriate cellobioside splitting enzyme basing on the present studies and the relevant literature."}
{"id": "PMID:10690", "title": "[On the age dependence of the intracellular proteolysis (author's transl)].", "content": "We report the age dependent changes of the proteolytic capacity of the rat liver at pH 3.0 and pH 6.0. The total proteolytic activity increases during the whole cycle. During the weanling period the specific activity (mug substrate split x min-1 X mg liver protein-1) rises up to values about 30% higher than those of the remaining lifetime. We found the specific activity in old male animals (18 months) to be lower than in younger ones (5 months). These findings are correct for the liver homogenate as well as for the cell fractions.", "contents": "[On the age dependence of the intracellular proteolysis (author's transl)]. We report the age dependent changes of the proteolytic capacity of the rat liver at pH 3.0 and pH 6.0. The total proteolytic activity increases during the whole cycle. During the weanling period the specific activity (mug substrate split x min-1 X mg liver protein-1) rises up to values about 30% higher than those of the remaining lifetime. We found the specific activity in old male animals (18 months) to be lower than in younger ones (5 months). These findings are correct for the liver homogenate as well as for the cell fractions."}
{"id": "PMID:10691", "title": "[Study of resistance to physical stress in pregnant women: influence of standardized work on cardiovascular system, ventilation, gaseous interchange, carbohydrate metabolism and acid-base balance (author's transl)].", "content": "10 women in the 12th week of pregnancy were tested with 50 and 60 watts on the bicycle ergometer; 16, in the 38th week of pregnancy and 12 weeks after delivery. Heart rate, blood pressure, O2 intake, CO2 elimination, respiration rate, respiratory volume per minute, lactate, pyruvate, glucose, pCO2, base excess and pH were measured at rest and under stress. Already in the 12th week of pregnancy (SSW), O2 intake and calorie consumption for the same work was significantly higher than in the nonpregnant subjects. Heart rate and blood pressure behaved the same during and outside of pregnancy. In the 38th week of pregnancy, the steady-state was reached later. O2 intake and calorie consumption were significantly increased. In pregnant women, the glucose level decreased about 11 mg% under stress while it remained constant in nonpregnant subjects. In pregnant women, lactate production is significantly higher (26%) during work. Metabolic acidosis cannot be compensated by respiration. The base deficit was significantly larger; pH was reduced. In pregnant women, physical stress produces increased respiration, CO2 consumption and calorie consumption are increased, CO2 deficit is greater and metabolic acidosis develops.", "contents": "[Study of resistance to physical stress in pregnant women: influence of standardized work on cardiovascular system, ventilation, gaseous interchange, carbohydrate metabolism and acid-base balance (author's transl)]. 10 women in the 12th week of pregnancy were tested with 50 and 60 watts on the bicycle ergometer; 16, in the 38th week of pregnancy and 12 weeks after delivery. Heart rate, blood pressure, O2 intake, CO2 elimination, respiration rate, respiratory volume per minute, lactate, pyruvate, glucose, pCO2, base excess and pH were measured at rest and under stress. Already in the 12th week of pregnancy (SSW), O2 intake and calorie consumption for the same work was significantly higher than in the nonpregnant subjects. Heart rate and blood pressure behaved the same during and outside of pregnancy. In the 38th week of pregnancy, the steady-state was reached later. O2 intake and calorie consumption were significantly increased. In pregnant women, the glucose level decreased about 11 mg% under stress while it remained constant in nonpregnant subjects. In pregnant women, lactate production is significantly higher (26%) during work. Metabolic acidosis cannot be compensated by respiration. The base deficit was significantly larger; pH was reduced. In pregnant women, physical stress produces increased respiration, CO2 consumption and calorie consumption are increased, CO2 deficit is greater and metabolic acidosis develops."}
{"id": "PMID:10697", "title": "[Relationship between thermal treatments of milk and molecular hysteresis of the milk protein system (author's transl)].", "content": "The potentiometric titration curve of milk does not show an equilibrium curve but a hysteresis loop between pH 6.2 und pH 4.8. Hysteresis means thermodynamic metastability and cooperative changes within a structural domain. The structural domain involved in these changes is the casein micelle. Cooperative conformation changes and thermodynamic metastability appear on the resolution of the casein micelle caused by the action of protons. The charge condition of the polypeptide chains is not synchron with the charge supply. The lag depends on the thermal treatment. Therefore the milk protein system can serve as a memory for physical datas.", "contents": "[Relationship between thermal treatments of milk and molecular hysteresis of the milk protein system (author's transl)]. The potentiometric titration curve of milk does not show an equilibrium curve but a hysteresis loop between pH 6.2 und pH 4.8. Hysteresis means thermodynamic metastability and cooperative changes within a structural domain. The structural domain involved in these changes is the casein micelle. Cooperative conformation changes and thermodynamic metastability appear on the resolution of the casein micelle caused by the action of protons. The charge condition of the polypeptide chains is not synchron with the charge supply. The lag depends on the thermal treatment. Therefore the milk protein system can serve as a memory for physical datas."}
{"id": "PMID:10693", "title": "[Different deoxyribonuclease-activities in bull seminal plasma (author's transl)].", "content": "By means of the in situ assay of deoxyribonucleases in DNA-containing polyacrylamide gels after separation by micro-disc-electrophoresis different deoxyribonucleases are detectable in bull seminal plasma. There are two groups of acid deoxyribonuclease-activities with a pH optimum at pH 5.0, one with a pH optimum at pH 7.4 and an additional one with a pH optimum at pH 8.5.", "contents": "[Different deoxyribonuclease-activities in bull seminal plasma (author's transl)]. By means of the in situ assay of deoxyribonucleases in DNA-containing polyacrylamide gels after separation by micro-disc-electrophoresis different deoxyribonucleases are detectable in bull seminal plasma. There are two groups of acid deoxyribonuclease-activities with a pH optimum at pH 5.0, one with a pH optimum at pH 7.4 and an additional one with a pH optimum at pH 8.5."}
{"id": "PMID:10695", "title": "[Effect of pregnancy on the functional state of the upper respiratory tracts].", "content": "The author studied the condition of various components responsible for the protective function of the upper respiratory tract mucous membrane as well as the olfactory sensibility in 439 pregnant women. She found certain regularities in the change of the motor, absorbing and secretory activity of the mucous membrane and olfactory sensibility, the calorific effect and the active reaction of the secrete being less characteristic. She emphasizes that the above changes cause the development of respiratory disorders in women during the period of pregnancy.", "contents": "[Effect of pregnancy on the functional state of the upper respiratory tracts]. The author studied the condition of various components responsible for the protective function of the upper respiratory tract mucous membrane as well as the olfactory sensibility in 439 pregnant women. She found certain regularities in the change of the motor, absorbing and secretory activity of the mucous membrane and olfactory sensibility, the calorific effect and the active reaction of the secrete being less characteristic. She emphasizes that the above changes cause the development of respiratory disorders in women during the period of pregnancy."}
{"id": "PMID:10696", "title": "[Basic principles of physiotherapy for allergic diseases of the otorhinolaryngologic organs].", "content": "Physiotherapy for allergic diseases of otorhinolaryngeal organs is often practiced without taking into consideration the stage of development of the pathologic process, its form and individual peculiarities of its course. This is partly connected with lack of data on the mechanism of the hyposensibilizing effect of physiofactors. In this paper the authors divide the methods of hyposensibilizing physiotherapy into groups according to their prevalent effect on the particular system taking part in the formation of clinical manifestations of the allergic reaction. The authors discuss the expediency of using each group of methods at various stages of the disease according to its form and individual peculiarities of its course.", "contents": "[Basic principles of physiotherapy for allergic diseases of the otorhinolaryngologic organs]. Physiotherapy for allergic diseases of otorhinolaryngeal organs is often practiced without taking into consideration the stage of development of the pathologic process, its form and individual peculiarities of its course. This is partly connected with lack of data on the mechanism of the hyposensibilizing effect of physiofactors. In this paper the authors divide the methods of hyposensibilizing physiotherapy into groups according to their prevalent effect on the particular system taking part in the formation of clinical manifestations of the allergic reaction. The authors discuss the expediency of using each group of methods at various stages of the disease according to its form and individual peculiarities of its course."}
{"id": "PMID:10701", "title": "[Glucose infusions in suspected chronic placental insufficiency caused by gestosis].", "content": "In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia.", "contents": "[Glucose infusions in suspected chronic placental insufficiency caused by gestosis]. In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia."}
{"id": "PMID:10702", "title": "Susceptibility of Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae to antibiotics. Comparison of patterns in Poland and Federal Republic of Germany.", "content": "One hundred and eighty five strains of Gram-positive cocci were tested for susceptibility to 16 antibiotics, including some newer drugs, by agar dilution technique. Of these, 100 strains (50 each isolated in Poland and Germany) were Staphylococcus aureus, 55 Streptococcus pyogenes, and 30 Diplococcus pneumoniae. Previous investigations of streptococci and pneumococci isolated in Poland and Federal Republic of Grmany, revealed no differences in antibiotic-susceptibility patterns in both countries, which was not the case with staphylococci. Present study demonstrates further evidence for existence of differences in antibiotic-sensitivity of staphylococci, depending of their geographical origin, and presents actual state of susceptibility to antibiotics of Streptococcus pyogenes and Diplococcus pneumoniae.", "contents": "Susceptibility of Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae to antibiotics. Comparison of patterns in Poland and Federal Republic of Germany. One hundred and eighty five strains of Gram-positive cocci were tested for susceptibility to 16 antibiotics, including some newer drugs, by agar dilution technique. Of these, 100 strains (50 each isolated in Poland and Germany) were Staphylococcus aureus, 55 Streptococcus pyogenes, and 30 Diplococcus pneumoniae. Previous investigations of streptococci and pneumococci isolated in Poland and Federal Republic of Grmany, revealed no differences in antibiotic-susceptibility patterns in both countries, which was not the case with staphylococci. Present study demonstrates further evidence for existence of differences in antibiotic-sensitivity of staphylococci, depending of their geographical origin, and presents actual state of susceptibility to antibiotics of Streptococcus pyogenes and Diplococcus pneumoniae."}
{"id": "PMID:10703", "title": "Sport training and some activities of human polymorphonuclear leukocyte lysosomes.", "content": "The acid phosphatase and protease, neutral protease, bactericidal and mitogenic activities were determined in the polymorphonuclear leukocyte (PMNL) lysosomes of 16 years old boys. The investigated group consisted of 20 intense sport training persons during the last six years, the control one of the same age boys without any sport training. The significant decrease of hydrolase activity has been observed in the lysosomes of the peripheral blood PMNL's of the sport training boys.", "contents": "Sport training and some activities of human polymorphonuclear leukocyte lysosomes. The acid phosphatase and protease, neutral protease, bactericidal and mitogenic activities were determined in the polymorphonuclear leukocyte (PMNL) lysosomes of 16 years old boys. The investigated group consisted of 20 intense sport training persons during the last six years, the control one of the same age boys without any sport training. The significant decrease of hydrolase activity has been observed in the lysosomes of the peripheral blood PMNL's of the sport training boys."}
{"id": "PMID:10705", "title": "[Enzymatic conversion of tetradecanol in heterogenous phase by yeast-alcohol dehydrogenase].", "content": "Alcohol dehydrogenase from yeast converts long-chain primary alcohols not only in the dissolved state, but also at the surface of undissolved particles. Tetradecanol beads with a defined surface can be produced and employed as model substrate. The reaction rate was determined by the proton release accomplished in the reaction. The initial reaction rate depends on the enzyme concentration. The relation is nonlinear (vi = k-[e]0,4); the numerical value of the exponent (n = 0.4) argues in favour of a reaction occurring at the interface. The Lineweaver-Burk plots become linear if the substrate concentrations are based on the molar surface concentrations of the particles. The pH optimum for the reaction at the surface is displaced by 0.25 pH units towards the alkaline region (compared with ethanol as substrate). The activation energy of the reaction with tetradecanol beads as substrate is 30% lower than that for the ethanol oxydation.", "contents": "[Enzymatic conversion of tetradecanol in heterogenous phase by yeast-alcohol dehydrogenase]. Alcohol dehydrogenase from yeast converts long-chain primary alcohols not only in the dissolved state, but also at the surface of undissolved particles. Tetradecanol beads with a defined surface can be produced and employed as model substrate. The reaction rate was determined by the proton release accomplished in the reaction. The initial reaction rate depends on the enzyme concentration. The relation is nonlinear (vi = k-[e]0,4); the numerical value of the exponent (n = 0.4) argues in favour of a reaction occurring at the interface. The Lineweaver-Burk plots become linear if the substrate concentrations are based on the molar surface concentrations of the particles. The pH optimum for the reaction at the surface is displaced by 0.25 pH units towards the alkaline region (compared with ethanol as substrate). The activation energy of the reaction with tetradecanol beads as substrate is 30% lower than that for the ethanol oxydation."}
{"id": "PMID:10706", "title": "[Structure-activity relationships of halogenated phenylethanolamine and phenoxypropanolamine].", "content": "12 compounds from the series of halogenated phenylethanolamines and phenoxypropanolamines were tested at the isolated rabbit jejunum, and the pD2-and pA2-values were determined. All the substances act beta-adrenolytically. Except for 3,4-dichloronoradrenaline, which stimulates the alpha-receptors, all the compounds still have pronounced beta-mimetic effects. The 2,5-dihalogenated phenylethanolamines and phenoxypropanolamines block the beta-receptors at lower concentrations than 2,4-dihalogen derivatives. The weakest beta-adrenolytic effects at the intestine were found with compounds halogenated at the 3,4-position.", "contents": "[Structure-activity relationships of halogenated phenylethanolamine and phenoxypropanolamine]. 12 compounds from the series of halogenated phenylethanolamines and phenoxypropanolamines were tested at the isolated rabbit jejunum, and the pD2-and pA2-values were determined. All the substances act beta-adrenolytically. Except for 3,4-dichloronoradrenaline, which stimulates the alpha-receptors, all the compounds still have pronounced beta-mimetic effects. The 2,5-dihalogenated phenylethanolamines and phenoxypropanolamines block the beta-receptors at lower concentrations than 2,4-dihalogen derivatives. The weakest beta-adrenolytic effects at the intestine were found with compounds halogenated at the 3,4-position."}
{"id": "PMID:10707", "title": "The binding of noradrenaline to human erythrocytes.", "content": "When human erythrocytes are incubated in a suspension medium containing noradrenaline, they take up noradrenaline in a reaction proceeding in two phases. In a rapid first reaction noradrenaline is bound by the cells by adsorption at pH-values above 6.0; this reaction follows Freundlich's isotherms. Subsequently, noradrenaline is taken up much more slowly by transmembranous diffusion into the cells. Neither reaction can be influenced by inhibitors such as N-ethyl maleinimide, ouabain, alpha- or beta-receptor blockers.", "contents": "The binding of noradrenaline to human erythrocytes. When human erythrocytes are incubated in a suspension medium containing noradrenaline, they take up noradrenaline in a reaction proceeding in two phases. In a rapid first reaction noradrenaline is bound by the cells by adsorption at pH-values above 6.0; this reaction follows Freundlich's isotherms. Subsequently, noradrenaline is taken up much more slowly by transmembranous diffusion into the cells. Neither reaction can be influenced by inhibitors such as N-ethyl maleinimide, ouabain, alpha- or beta-receptor blockers."}
{"id": "PMID:10708", "title": "[Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value].", "content": "The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time.", "contents": "[Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]. The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time."}
{"id": "PMID:10709", "title": "On the behaviour of murine lymphocytes after in vitro treatment with acid mucoproteins from human serum.", "content": "Seromucoproteins from human serum were isolated by perchloric acid extraction followed by DEAE-Sephadex A-50 ion exchange chromatography. The in vitro pretreatment of spleen leukocytes with this fraction caused a dose-dependent inhibition of graft-versus-host reaction as well as an increase of their electrophoretic mobility, the viability being maintained. On contrary, the pretreatment of mice (prospective spleen cell donors of recipients of sheep red blood cells) with human seromucoproteins had no effect on the gvh-reaction as well as on the agglutinin formation to sheep red blood cells under the given conditions. It is supposed that the suppressive effect after in vitro pretreatment may be attributed to a coating effect of seromucoproteins. The fact that spleen cells pretreated in vitro with seromucoproteins are lysed in presence of complement and antiseromucoprotein antiserum supports our opinion. These findings as well as data from the literature support the hypothesis that local concentrated mucoproteins in the skin graft bed in cases of protractedly surviving skin grafts, in the placenta, and on neoplastic tissues can influence unspecifically the immune response. We hope that the understanding of this mechanism may open new possibilities in prolonging allograft survival time.", "contents": "On the behaviour of murine lymphocytes after in vitro treatment with acid mucoproteins from human serum. Seromucoproteins from human serum were isolated by perchloric acid extraction followed by DEAE-Sephadex A-50 ion exchange chromatography. The in vitro pretreatment of spleen leukocytes with this fraction caused a dose-dependent inhibition of graft-versus-host reaction as well as an increase of their electrophoretic mobility, the viability being maintained. On contrary, the pretreatment of mice (prospective spleen cell donors of recipients of sheep red blood cells) with human seromucoproteins had no effect on the gvh-reaction as well as on the agglutinin formation to sheep red blood cells under the given conditions. It is supposed that the suppressive effect after in vitro pretreatment may be attributed to a coating effect of seromucoproteins. The fact that spleen cells pretreated in vitro with seromucoproteins are lysed in presence of complement and antiseromucoprotein antiserum supports our opinion. These findings as well as data from the literature support the hypothesis that local concentrated mucoproteins in the skin graft bed in cases of protractedly surviving skin grafts, in the placenta, and on neoplastic tissues can influence unspecifically the immune response. We hope that the understanding of this mechanism may open new possibilities in prolonging allograft survival time."}
{"id": "PMID:10712", "title": "Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin.", "content": "Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.", "contents": "Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin. Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride."}
{"id": "PMID:10714", "title": "High uptake in the erythrocytes and the spleen of the quaternary dipyridylium salt paraquat injected intravenously in hypotonic solutions.", "content": "Intravenous injections of the quaternary dipyridlium salt paraquat (14C-labelled) dissolved in solutions of low tonicity result in a high uptake in the erythrocytes and concomitantly also in the spleen (red pulp), the latter being probably due to phagocytosis of paraquat-containing erythrocytes by the reticuloendothelial system. Higher tonicities of the injected solutions result in a low uptake and the same applies to oral, intraperitoneal and subcutaneous injections. Paraquat was present in the erythrocytes in a non-metabolized form without being bound to membranes or proteins. The uptake in the erythrocytes was not influenced by alterations of the pH or by the preparation of a charge-transfer complex with serotonin in the injection solutions. Chemical alterations of the paraquat in the injection solutions could not be detected. In vitro the uptake of paraquat in the erythrocytes was higher in the haemolysed (and then reconstituted by adding sodium chloride) erythrocyte-ghosts than in the non-haemolysed erythrocytes, as shown by incubations at various tonicities. It is proposed that the intravenous injections of paraquat in hypotonic solutions temporarily alter the membranes of the erythrocytes in the blood-stream and make them permeable to paraquat, possibly, as judged from the in vitro experiments, only during a short period of partial haemolysis. The distribution studies also showed a retention of paraquat in the lungs. In addition paraquat was accumulated in the melanin of the tissues.", "contents": "High uptake in the erythrocytes and the spleen of the quaternary dipyridylium salt paraquat injected intravenously in hypotonic solutions. Intravenous injections of the quaternary dipyridlium salt paraquat (14C-labelled) dissolved in solutions of low tonicity result in a high uptake in the erythrocytes and concomitantly also in the spleen (red pulp), the latter being probably due to phagocytosis of paraquat-containing erythrocytes by the reticuloendothelial system. Higher tonicities of the injected solutions result in a low uptake and the same applies to oral, intraperitoneal and subcutaneous injections. Paraquat was present in the erythrocytes in a non-metabolized form without being bound to membranes or proteins. The uptake in the erythrocytes was not influenced by alterations of the pH or by the preparation of a charge-transfer complex with serotonin in the injection solutions. Chemical alterations of the paraquat in the injection solutions could not be detected. In vitro the uptake of paraquat in the erythrocytes was higher in the haemolysed (and then reconstituted by adding sodium chloride) erythrocyte-ghosts than in the non-haemolysed erythrocytes, as shown by incubations at various tonicities. It is proposed that the intravenous injections of paraquat in hypotonic solutions temporarily alter the membranes of the erythrocytes in the blood-stream and make them permeable to paraquat, possibly, as judged from the in vitro experiments, only during a short period of partial haemolysis. The distribution studies also showed a retention of paraquat in the lungs. In addition paraquat was accumulated in the melanin of the tissues."}
{"id": "PMID:10711", "title": "Morphology and enzyme aktivity in rat small intestinal epithelium 6 and 12 hrs. after an alkylating agent (cyclophosphamide).", "content": "Six and twelve hours after a single i.p. dose of cyclophosphamide (100 mg/kg body weight) the activity of different \"brush border enzymes\" (maltase, sucrase lactase, alkaline phosphatase, gamma-glutamyl transferase) and of a lysosomal enzyme (acid phosphatase) did not change. In vivo absorption of galactose was not diminished by the treatment. The pattern of response to cyclophosphamide seems to be different in SPF and GF rats. The response of crypt epithelium (cell number, mitotic number, mitotic frequency) was more pronounced in the SPF rats, whereas the villus height only decreased in the GF rats.", "contents": "Morphology and enzyme aktivity in rat small intestinal epithelium 6 and 12 hrs. after an alkylating agent (cyclophosphamide). Six and twelve hours after a single i.p. dose of cyclophosphamide (100 mg/kg body weight) the activity of different \"brush border enzymes\" (maltase, sucrase lactase, alkaline phosphatase, gamma-glutamyl transferase) and of a lysosomal enzyme (acid phosphatase) did not change. In vivo absorption of galactose was not diminished by the treatment. The pattern of response to cyclophosphamide seems to be different in SPF and GF rats. The response of crypt epithelium (cell number, mitotic number, mitotic frequency) was more pronounced in the SPF rats, whereas the villus height only decreased in the GF rats."}
{"id": "PMID:10715", "title": "Hypertension in end-stage renal disease. The relationship between blood pressure, plasma renin, plasma renin substrate and exchangeable sodium in chronic hemodialysis patients.", "content": "Blood pressure (BP), plasma renin concentration (PRC), plasma renin substrate concentration (PRSC) and exchangeable sodium (ES) have been studied in 27 patients undergoing regular hemodialysis because of end-stage renal disease. PRC was significantly higher in the hypertensive than in the normotensive patients. The pattern of PRSC was similar in the groups of patients but with a marked individual variation. ES was slightly lower in the hypertensives than in the normotensives but the difference was not statistically significant. Multiple regression analysis demonstrated a significant correlation between mean BP, the natural logarithm of PRC and ES, but the effect of ES was negligible. PRC was negatively correlated to ES in all patients, including the hypertensives. These results strongly suggest that the renin-angiotensin system is the most important factor involved in the pathogenesis of hypertension in end-stage renal disease, when sodium balance is adequately controlled. A clinical application of the predictive value of PRC concerning the effect of bilateral nephrectomy on hypertension is outlined.", "contents": "Hypertension in end-stage renal disease. The relationship between blood pressure, plasma renin, plasma renin substrate and exchangeable sodium in chronic hemodialysis patients. Blood pressure (BP), plasma renin concentration (PRC), plasma renin substrate concentration (PRSC) and exchangeable sodium (ES) have been studied in 27 patients undergoing regular hemodialysis because of end-stage renal disease. PRC was significantly higher in the hypertensive than in the normotensive patients. The pattern of PRSC was similar in the groups of patients but with a marked individual variation. ES was slightly lower in the hypertensives than in the normotensives but the difference was not statistically significant. Multiple regression analysis demonstrated a significant correlation between mean BP, the natural logarithm of PRC and ES, but the effect of ES was negligible. PRC was negatively correlated to ES in all patients, including the hypertensives. These results strongly suggest that the renin-angiotensin system is the most important factor involved in the pathogenesis of hypertension in end-stage renal disease, when sodium balance is adequately controlled. A clinical application of the predictive value of PRC concerning the effect of bilateral nephrectomy on hypertension is outlined."}
{"id": "PMID:10716", "title": "A new pattern of multiple endocrine adenomatosis: chemodectoma, bronchial carcinoid, GH-producing pituitary adenoma, and hyperplasia of the parathyroid glands, and antral and duodenal gastrin cells.", "content": "A female patient was found to have a chemodectoma, a GH-producing pituitary tumour and a bronchial carcinoid combined with hyperplasia of the parathyroids and of antral and duodenal gastrin cells. This combination of endocrine tumours and hyperplasias does not fit with the two multiple endocrine adenomatosis syndromes recognized at present. The case stresses the importance of scanning the patient for other endocrine tumours, once one has been diagnosed.", "contents": "A new pattern of multiple endocrine adenomatosis: chemodectoma, bronchial carcinoid, GH-producing pituitary adenoma, and hyperplasia of the parathyroid glands, and antral and duodenal gastrin cells. A female patient was found to have a chemodectoma, a GH-producing pituitary tumour and a bronchial carcinoid combined with hyperplasia of the parathyroids and of antral and duodenal gastrin cells. This combination of endocrine tumours and hyperplasias does not fit with the two multiple endocrine adenomatosis syndromes recognized at present. The case stresses the importance of scanning the patient for other endocrine tumours, once one has been diagnosed."}
{"id": "PMID:10717", "title": "Multiple endocrine adenomatosis of mixed type.", "content": "A case of multiple endocrine adenomatosis (MEA) of mixed type is presented. The syndrome, observed in a 65 year-old female, consisted of multiple neurofibroadenomatosis, medullary thyroid carcinoma, multiple adenomata of the parathyroids, adrenal cortical adenoma and small cell anaplastic bronchogenic carcinoma. Thus, it was composed of type 1 as well as of type 2 MEA. On the basis of another seven cases, collected from the literature, the MEA syndrome of mixed type is reviewed with special reference to the phylogenetic origin of the cells of the APUD system.", "contents": "Multiple endocrine adenomatosis of mixed type. A case of multiple endocrine adenomatosis (MEA) of mixed type is presented. The syndrome, observed in a 65 year-old female, consisted of multiple neurofibroadenomatosis, medullary thyroid carcinoma, multiple adenomata of the parathyroids, adrenal cortical adenoma and small cell anaplastic bronchogenic carcinoma. Thus, it was composed of type 1 as well as of type 2 MEA. On the basis of another seven cases, collected from the literature, the MEA syndrome of mixed type is reviewed with special reference to the phylogenetic origin of the cells of the APUD system."}
{"id": "PMID:10720", "title": "Current dimensions of the endocrine system.", "content": "The basic and clinical sciences have become fused in the investigation of relatively new syndromes and their pathogenesis. The measurement of hormone content in serum and tissues and the elucidation of its biologic effect via the membrane and cytoplasmic receptors leads to diagnostic and prognostic accuracy. New breakthrough advances in clinical and cellular phenomena will portend new horizons for more specific diagnoses and modern treatment of present and new endocrinopathies. The dimensions of the neuroendocrine system are expanding; the future perimeters are beyond sight today.", "contents": "Current dimensions of the endocrine system. The basic and clinical sciences have become fused in the investigation of relatively new syndromes and their pathogenesis. The measurement of hormone content in serum and tissues and the elucidation of its biologic effect via the membrane and cytoplasmic receptors leads to diagnostic and prognostic accuracy. New breakthrough advances in clinical and cellular phenomena will portend new horizons for more specific diagnoses and modern treatment of present and new endocrinopathies. The dimensions of the neuroendocrine system are expanding; the future perimeters are beyond sight today."}
{"id": "PMID:10722", "title": "Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor.", "content": "The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.", "contents": "Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor. The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians."}
{"id": "PMID:10724", "title": "Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.", "content": "The residual hexosaminidase isoenzymes in juvenile Sandhoff and infantile Sandhoff disease fibroblasts, have been determined by starch gel electrophoresis and column isoelectric focusing. Hex A and hex S are the major residual isozymes in fibroblasts from the juvenile patient, while hex B is barely detectable. Only hex S could be detected in fibroblasts from infantile Sandhoff patients. These results suggest that the defects in juvenile and infantile Sandhoff disease may be different allelic modifications of the beta subunit common to hex A and hex B.", "contents": "Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts. The residual hexosaminidase isoenzymes in juvenile Sandhoff and infantile Sandhoff disease fibroblasts, have been determined by starch gel electrophoresis and column isoelectric focusing. Hex A and hex S are the major residual isozymes in fibroblasts from the juvenile patient, while hex B is barely detectable. Only hex S could be detected in fibroblasts from infantile Sandhoff patients. These results suggest that the defects in juvenile and infantile Sandhoff disease may be different allelic modifications of the beta subunit common to hex A and hex B."}
{"id": "PMID:10725", "title": "Effect of sodium depletion on plasma renin concentration before and during adrenergic beta-receptor blockade with propranolol in normotensive man.", "content": "Plasma renin levels have been used to discriminate between different forms of hypertension, but how to define the normal range of plasma renin levels has not been agreed upon. Sodium depletion stimulates renin release. Evaluation of plasma renin would, therefore seem possible only in relation to sodium balance. Plasma renin concentration and concurrent daily sodium excretion were determined in 33 healthy normotensive subjects (control group) ingesting high, normal and low sodium diets. A well-defined hyperbolic relationship was found between the two variables indicating that the physiologic level of plasma renin concentration depends on the state of sodium balance. An increase in plasma potassium concentration may reduce plasma renin concentration, but this appeared to be overruled by the stimulating effect of sodium depletion. To examine whether beta-adrenergic stimulation contributes to the increase in plasma renin concentration during sodium depletion, the relationship between plasma renin concentration and concurrent sodium excretion was studied during beta-receptor blockade with propranolol. In 20 healthy normotensive subjects in whom beta-receptor blockade was verified by a significant reduction in pulse rate, the same hyperbolic relationship was found between plasma renin concentration and sodium excretion as in the control group showing that sodium depletion stimulates renin release independent of sympathetic nervous activity.", "contents": "Effect of sodium depletion on plasma renin concentration before and during adrenergic beta-receptor blockade with propranolol in normotensive man. Plasma renin levels have been used to discriminate between different forms of hypertension, but how to define the normal range of plasma renin levels has not been agreed upon. Sodium depletion stimulates renin release. Evaluation of plasma renin would, therefore seem possible only in relation to sodium balance. Plasma renin concentration and concurrent daily sodium excretion were determined in 33 healthy normotensive subjects (control group) ingesting high, normal and low sodium diets. A well-defined hyperbolic relationship was found between the two variables indicating that the physiologic level of plasma renin concentration depends on the state of sodium balance. An increase in plasma potassium concentration may reduce plasma renin concentration, but this appeared to be overruled by the stimulating effect of sodium depletion. To examine whether beta-adrenergic stimulation contributes to the increase in plasma renin concentration during sodium depletion, the relationship between plasma renin concentration and concurrent sodium excretion was studied during beta-receptor blockade with propranolol. In 20 healthy normotensive subjects in whom beta-receptor blockade was verified by a significant reduction in pulse rate, the same hyperbolic relationship was found between plasma renin concentration and sodium excretion as in the control group showing that sodium depletion stimulates renin release independent of sympathetic nervous activity."}
{"id": "PMID:10721", "title": "[Etiopathogenesis of necrotizing arteritis (leukocytoclastic vasculitis)].", "content": "The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Sch\u00f6nlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarc\u00f3n-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Sch\u00f3nlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Sch\u00f3nlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found...", "contents": "[Etiopathogenesis of necrotizing arteritis (leukocytoclastic vasculitis)]. The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Sch\u00f6nlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarc\u00f3n-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Sch\u00f3nlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Sch\u00f3nlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found..."}
{"id": "PMID:10727", "title": "Methodologic problems in plasma renin activity measurements.", "content": "The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity.", "contents": "Methodologic problems in plasma renin activity measurements. The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity."}
{"id": "PMID:10728", "title": "Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects.", "content": "We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual \"concentration\" of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors.", "contents": "Plasma prorenin: cryoactivation and relationship to renin substrate in normal subjects. We previously demonstrated an inactive form of renin, termed prorenin, in the plasma of normal, hypertensive and anephric patients. Prorenin activity can be determined in plasma from the total renin activity after activation, minus the prior endogenous plasma renin activity. In the present study, conditions for cryoactivation of prorenin have been defined. Plasma prorenin is slowly converted to active renin-like material at -5 degrees C at pH 7.4. Activation takes four days and does not occur at pH 5.0. The degree of activation increases above pH 5 and is greatest between pH 7 and pH 9. Thus, almost no cryoactivation of prorenin occurs at the pH optimum for renin (5.7) in contrast to maximum activation at pH 7.4. No activation has been observed in the frozen state, but it does occur with decreasing rapidity at temperatures from -5 degress to +4 degress C. Since blood samples obtained for the determination of plasma renin activity are routinely chilled upon collection by most laboratories, some activatin of prorenin most likely occurs in all routine renin assays. The pH optimum of the enzymatic reaction of the activated prorenin in plasma is 5.8, the same as for renal renin, and the shape of the pH optimum curve is similar to that of renal renin added to human plasma. In a group of 23 normal subjects with plasma renin activity of 3.5 +/- 2.9 (SD), the activated prorenin increment was found to be significantly higher, 6.3 +/- 5.0 (SD) ng/ml/hour. Unlike plasma renin activity, prorenin activity in these normal subjects was directly related to the concentration of renin substrate (p less than 0.001). When the actual \"concentration\" of prorenin was calculated using renal renin as the reference standard, a direct relationship was also found between the concentration of prorenin and renin substrate (p less than 0.01). The observed relationship between prorenin and renin substrate concentrations might be a consequence of their regulation by common factors."}
{"id": "PMID:10729", "title": "Beta-adrenergic receptor blocking drugs in spontaneous hypertension.", "content": "Eleven beta-adrenergic receptor blocking agents and derivatives were evaluated for their ability to affect systolic arterial blood pressure and pulse rate in unanesthetized, male spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls. Animals ranged from 7 to 76 weeks of age. The subcutaneous injection of 5 and 45 mg/kg metoprolol in 52 to 64 week old SHRs and 45 mg/kg twice a day to 26 to 29 week old SHRs produced a significant decrease in blooc pressure. The subcutaneous injection of pindolol (0.1 and 1.0 mg/kg) produced a greater and more consistent depressor effect in mature SHRs. The subcutaneous administration of sotalol (100 mg/kg) and alprenolol (20 mg/kg) resulted in a depressor action which was significant 120 minutes after injection of the drug. In the doses used, propranolol, oxprenolol, 4-hydroxypropranolol and K9-1366 produced pressor effect in SHRs. Propranolol did not cause this pressor effect in prehypertensive (seven week old) SHRs. Practolol, dextro-propranolol and KO-1313 had no effect on blood pressure in the doses used. Propranolol, pindolol, metoprolol, dextro-propranolol, 4-hydroxypropranolol, practolol, oxprenolol, KO-1366 and KO-1313 produced no significant effects on blood pressure in normotensive WKY controls in the doses tested. Placing oral doses of 160 mg/kg/day of metoprolol in the drinking water for seven days significantly lowered blood pressure in 14 week old SHRs previously exposed to ineffective doses of 77 mg/kg/day for 24 days. The administration of oral doses of oxprenolol (40 mg/kg/day) in drinking water for three weeks had a slight but insignificant pressor effect. Smaller doses of metoprolol (15 and 39 mg/kg/day for three to four weeks) and practolol (70 to 85 mg/kg/day for two weeks) had no effect on 52 week old SHRs. Oral doses of pindolol, metoprolol, practolol and oxprenolol had no significant effect on blood pressure in WKY controls. There was no clear relationship between the effects of the drugs on blood pressure and their ability to affect the pulse rate. Similarly, there did not appear to be any consistent relationship between the potency of the beta-blocking drug and the blood pressure lowering action. In addition, neither cardioselective beta-blockade nor sympathomimetic properties allowed the prediction of blood pressure responses to the administration of those agents possessing these features. Although SHRs provide a valuable model of human essential hypertension, the variable effects reported here and elsewhere in the literature require caution as to the applicability and usefulness of testing and evaluating beta-adrenergic blocking drugs for theri potential anti-hypertensive effects in this particular form of experimental hypertension.", "contents": "Beta-adrenergic receptor blocking drugs in spontaneous hypertension. Eleven beta-adrenergic receptor blocking agents and derivatives were evaluated for their ability to affect systolic arterial blood pressure and pulse rate in unanesthetized, male spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) controls. Animals ranged from 7 to 76 weeks of age. The subcutaneous injection of 5 and 45 mg/kg metoprolol in 52 to 64 week old SHRs and 45 mg/kg twice a day to 26 to 29 week old SHRs produced a significant decrease in blooc pressure. The subcutaneous injection of pindolol (0.1 and 1.0 mg/kg) produced a greater and more consistent depressor effect in mature SHRs. The subcutaneous administration of sotalol (100 mg/kg) and alprenolol (20 mg/kg) resulted in a depressor action which was significant 120 minutes after injection of the drug. In the doses used, propranolol, oxprenolol, 4-hydroxypropranolol and K9-1366 produced pressor effect in SHRs. Propranolol did not cause this pressor effect in prehypertensive (seven week old) SHRs. Practolol, dextro-propranolol and KO-1313 had no effect on blood pressure in the doses used. Propranolol, pindolol, metoprolol, dextro-propranolol, 4-hydroxypropranolol, practolol, oxprenolol, KO-1366 and KO-1313 produced no significant effects on blood pressure in normotensive WKY controls in the doses tested. Placing oral doses of 160 mg/kg/day of metoprolol in the drinking water for seven days significantly lowered blood pressure in 14 week old SHRs previously exposed to ineffective doses of 77 mg/kg/day for 24 days. The administration of oral doses of oxprenolol (40 mg/kg/day) in drinking water for three weeks had a slight but insignificant pressor effect. Smaller doses of metoprolol (15 and 39 mg/kg/day for three to four weeks) and practolol (70 to 85 mg/kg/day for two weeks) had no effect on 52 week old SHRs. Oral doses of pindolol, metoprolol, practolol and oxprenolol had no significant effect on blood pressure in WKY controls. There was no clear relationship between the effects of the drugs on blood pressure and their ability to affect the pulse rate. Similarly, there did not appear to be any consistent relationship between the potency of the beta-blocking drug and the blood pressure lowering action. In addition, neither cardioselective beta-blockade nor sympathomimetic properties allowed the prediction of blood pressure responses to the administration of those agents possessing these features. Although SHRs provide a valuable model of human essential hypertension, the variable effects reported here and elsewhere in the literature require caution as to the applicability and usefulness of testing and evaluating beta-adrenergic blocking drugs for theri potential anti-hypertensive effects in this particular form of experimental hypertension."}
{"id": "PMID:10730", "title": "Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol.", "content": "A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition.  In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated.", "contents": "Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol. A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition.  In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated."}
{"id": "PMID:10731", "title": "Controlled trial of fetal intensive care.", "content": "A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified.", "contents": "Controlled trial of fetal intensive care. A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified."}
{"id": "PMID:10732", "title": "Other hydrophilic lens environments: pH.", "content": "Although hydrophilic contact lenses are specifically designed for compatibility with the eye environment, i.e., the tears, they will, with the exception of continuous wear types, spend a significant fraction of their daily cycle in other solutions. This investigation explores the pH characteristics of certain of those alternative media.", "contents": "Other hydrophilic lens environments: pH. Although hydrophilic contact lenses are specifically designed for compatibility with the eye environment, i.e., the tears, they will, with the exception of continuous wear types, spend a significant fraction of their daily cycle in other solutions. This investigation explores the pH characteristics of certain of those alternative media."}
{"id": "PMID:10733", "title": "Participation of H1 and H2 histamine receptors in physiological vasodilator responses.", "content": "Histamine causes vasodilation in the dog by activation of H1 and H2 receptors blocked by mepyramine and metiamide, respectively. Experiments were conducted in anesthetized dogs to determine the participation of H1 and H2 receptors in several forms of physiological dilatation. Mepyramine attenuated both histamine-induced and active-reflex dilatation in the hindlimb. Metiamide caused a further reduction in both sets of dilatation. Neither single nor combined antihistamines reduced dilatation due to exercise or after temporary occlusion of the circulation in the hindlimb. Poststimulation dilatation in the gracilis muscle was partially attenuated by metiamide or mepyramine. Neither dilatation caused by sympathetic nerve stimulation in the hindpaw nor dilatation in the gracilis muscle caused by compound 48/80 was reduced by mepyramine. Following combined H1- and H2-receptor blockade, portions of both types of dilatation were reduced. These data provide evidence for the participation of both types of histamine receptor in active reflex dilatation, low-frequency neurogenic dilatation, dilatation caused by compound 48/80, and poststimulation dilatation. Neither type of histamine receptor appears to be involved in reactive hyperemia or dilatation caused by exercise.", "contents": "Participation of H1 and H2 histamine receptors in physiological vasodilator responses. Histamine causes vasodilation in the dog by activation of H1 and H2 receptors blocked by mepyramine and metiamide, respectively. Experiments were conducted in anesthetized dogs to determine the participation of H1 and H2 receptors in several forms of physiological dilatation. Mepyramine attenuated both histamine-induced and active-reflex dilatation in the hindlimb. Metiamide caused a further reduction in both sets of dilatation. Neither single nor combined antihistamines reduced dilatation due to exercise or after temporary occlusion of the circulation in the hindlimb. Poststimulation dilatation in the gracilis muscle was partially attenuated by metiamide or mepyramine. Neither dilatation caused by sympathetic nerve stimulation in the hindpaw nor dilatation in the gracilis muscle caused by compound 48/80 was reduced by mepyramine. Following combined H1- and H2-receptor blockade, portions of both types of dilatation were reduced. These data provide evidence for the participation of both types of histamine receptor in active reflex dilatation, low-frequency neurogenic dilatation, dilatation caused by compound 48/80, and poststimulation dilatation. Neither type of histamine receptor appears to be involved in reactive hyperemia or dilatation caused by exercise."}
{"id": "PMID:10734", "title": "Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect.", "content": "Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate.", "contents": "Maleate-induced bicarbonaturia in the dog: a carbonic anhydrase-independene effect. Studies were performed to characterize the renal effects of maleate in anesthetized dogs. Following the intravenous administration of maleate or maleic acid (50 mg/kg), mean fractional bicarbonate excretion (CHCO3/GFR) rose to as high as 26%. Na, K, and phosphate excretion also increased markedly, whereas C1 excretion remained low. An initial transient fall in urinary pH from 6.53 to 6.13 contrasted sharply with the rapid alkalinization of the urine induced by acetazolamide administration. During saline expansion CHCO3/GFR rose from 4 to 37% after maleate administration, whereas Cl excretion did not change significantly. During continuous carbonic anhydrase inhibition with acetazolamide, maleate administration resulted in a further rise in CHCO3/GFR from 22 to 35%. Whereas CPO4/GFR increased only from 1 to 3% during acetazolamide administration, this ratio reached 75% following the addition of maleate. Fumarate, the transisomer of maleate, and malonate, a well-known inhibitor of Krebs cycle, failed to affect bicarbonate excretion. This study demonstrates that maleate inhibits the fraction of bicarbonate reabsorption uncatalyzed by carbonic anhydrase. Impaired anionic reabsorption of bicarbonate or accelerated passive backflux of this ion into proximal tubular lumen are the two mechanisms that best explain the bicarbonaturia induced by maleate."}
{"id": "PMID:10735", "title": "Tetanic hyperpolarization of single medullated nerve fibers in sodium and lithium.", "content": "Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping.", "contents": "Tetanic hyperpolarization of single medullated nerve fibers in sodium and lithium. Repetitive stimulation of a single medullated nerve fiber of Xenopus yields a succession of postspike voltage-time curves which are nearly coincident until attainment of a voltage that corresponds to that of the maximum attained by the normal postspike undershoot. Initially the interspike potential returns toward a resting level after this brief phase of hyperpolarization. However, as tetanization proceeds, a pattern of hyperpolarization develops with the result that, in the tetanic steady state, there exists a progressive hyperpolarization throughout each interspike interval. Extent of postspike hyperpolarization in terms of a deviation deltaVm from the resting level of membrane potential is approximated by the variation deltaVm = delta[MNa + MK]/[GNa + GK] where MNa and MK are current densities associated with active pumping of sodium and potassium ions and GNa and GK are corresponding time-dependent leak conductances. Tetanic hyperpolarization is reversibly abolished by cyanide and by exposure to lithium Ringer. Eventual reappearance of tetanic hyperpolarization in the presence of lithium Ringer suggests lithium pumping."}
{"id": "PMID:10736", "title": "Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat.", "content": "Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated.", "contents": "Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. Glutamine synthetase (GS) is known to exist in the kidney of the rat, guinea pig, rabbit, and sheep but not in that of the dog, pig, cat, or pigeon. No data is available in man. Assay of histologically normal renal tissue obtained in human subjects during surgery for abdominal vascular disease failed to demonstrate significant GS activity. In addition, L-glutamine gamma-glutamyltransferase (GT) activity was also very low. The same results were observed in the dog, in which both GS and GT activities did not exceed 15% of those found in the kidney of the normal rat. In the latter animal both GS and GT activities are higher in the outer medulla (312 and 1,165 mumol/h per g wet wt, respectively) than in the cortex (230 and 844, respectively). During metabolic acidosis, GT activity did not change but GS activity decreased in the outer medulla by 40%. When renal cortex slices from normal rats were incubated in the presence of ammonia, glutamate, and octanoate (as a source of ATP), net synthesis of glutamine was readily demonstrated in contrast to slices from normal DOGS. The present studies demonstrate that the kidney of man, like that of the dog, is devoid of significant glutamine synthetase and glutamine gamma-glutamyltransferase activities. In the rat, we have confirmed the functional significance of GS activity in the kidney. We have also shown that renal GT activity is ammoniagenic in vitro in this animal, but the contribution of this system to total ammonia production in vivo remains to be demonstrated."}
{"id": "PMID:10737", "title": "Calcium uptake by subcellular fractions of human umbilical artery.", "content": "Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2.", "contents": "Calcium uptake by subcellular fractions of human umbilical artery. Two different mechanisms for the active accumulation of Ca2+ by subcellular fractions of human umbilical artery are described. One, located in the mitochondrial fraction, was induced by exogenous ATP or respiratory substrates (ADP and succinate) and was inhibited by azide. The other, located in the microsomal fraction, was induced by ATP and potentiated by oxalate, but not inhibited by azide. Increasing ATP concentrations up to 4-5 mM increased microsomal Ca2+ accumulation, whereas increasing ATP concentration above 2-3 mM caused inhibition of mitochondrial Ca2+ uptake. Although changing pH from 7.4 to 7.2 had no effect on mitochondrial Ca2+ accumulation, it doubled microsomal uptake. Neither adenosine 3',5'-monophosphate nor guanosine 3',5'-monophosphate in the presence or absence of protein kinase and kinase modulator affected Ca2+ uptake by or phosphorylation of the subcellular fractions. Partially purified protein kinases from umbilical and beef skeletal muscle contained a component(s) distinguishable from the kinase on the basis of its heat stability that enhanced ATP-induced Ca2+ uptake by mitochondrial fractions from the umbilical artery. It is suggested that alterations in Ca2+ sequestration induced by changes in ATP concentration and intracellular pH in mitochondrial and microsomal fractions, respectively, could play a role in the control of arterial patency and closure with changes in PO2."}
{"id": "PMID:10738", "title": "Intrarenal blood flow distribution in the desert quail following salt loading.", "content": "The total-kidney glomerular filtration rate (GFR) falls when birds are salt loaded. This fall in GFR is caused by glomerular intermittency. The nephrons that stop filtering are small, surface nephrons without loops of Henle. Larger nephrons with loops of Henle in the deeper regions of the kidney continue to filter during salt loading. Microfil casts were made of the renal microvasculature of the desert quail, Lophortyx gambelii, in an attempt to determine at what points intrarenal blood flow is regulated to cause glomerular intermittency. Casts of the renal vasculature were made in quail that were hydrated and in quail that were salt loaded. The results indicate that the small, surface nephrons stop filtering during salt loading because of a vasoconstriction at the level of the afferent arterioles of these nephrons. At the same time, blood flow is maintained to the large nephrons with loops of Henle. Reducing GFR at the expenses of excreting wastes can be viewed as a mechanism to conserve body water during periods of water deprivation.", "contents": "Intrarenal blood flow distribution in the desert quail following salt loading. The total-kidney glomerular filtration rate (GFR) falls when birds are salt loaded. This fall in GFR is caused by glomerular intermittency. The nephrons that stop filtering are small, surface nephrons without loops of Henle. Larger nephrons with loops of Henle in the deeper regions of the kidney continue to filter during salt loading. Microfil casts were made of the renal microvasculature of the desert quail, Lophortyx gambelii, in an attempt to determine at what points intrarenal blood flow is regulated to cause glomerular intermittency. Casts of the renal vasculature were made in quail that were hydrated and in quail that were salt loaded. The results indicate that the small, surface nephrons stop filtering during salt loading because of a vasoconstriction at the level of the afferent arterioles of these nephrons. At the same time, blood flow is maintained to the large nephrons with loops of Henle. Reducing GFR at the expenses of excreting wastes can be viewed as a mechanism to conserve body water during periods of water deprivation."}
{"id": "PMID:10739", "title": "Inhibition of inotropic effect of hyperosmotic mannitol by lactate in vitro.", "content": "Isolated, isometrically contracting cat papillary muscles were used to evaluate the inotropic interactions of lactic acidosis, hypercarbic acidosis, and lactate ion with hypertonic mannitol. These studies have documented that both lactic acidosis (pH less than 7.0) and lactate ion at a normal pH inhibit the inotropic effect of hyperosmotic mannitol in vitro. In contrast, hypercarbic acidosis does not prevent the inotropic effect of mannitol. Inhibition by lactic acid of mannitol's effects on contractility persists in the presence of beta-receptor blockade. The results suggest that inhibition by severe lactic acidosis of the direct inotropic effect of hyperosmolality in isolated cardiac muscle is mediated by lactate ion rather than acidosis per se.", "contents": "Inhibition of inotropic effect of hyperosmotic mannitol by lactate in vitro. Isolated, isometrically contracting cat papillary muscles were used to evaluate the inotropic interactions of lactic acidosis, hypercarbic acidosis, and lactate ion with hypertonic mannitol. These studies have documented that both lactic acidosis (pH less than 7.0) and lactate ion at a normal pH inhibit the inotropic effect of hyperosmotic mannitol in vitro. In contrast, hypercarbic acidosis does not prevent the inotropic effect of mannitol. Inhibition by lactic acid of mannitol's effects on contractility persists in the presence of beta-receptor blockade. The results suggest that inhibition by severe lactic acidosis of the direct inotropic effect of hyperosmolality in isolated cardiac muscle is mediated by lactate ion rather than acidosis per se."}
{"id": "PMID:10740", "title": "Renal hydrogen ion secretion after release of unilateral ureteral obstruction.", "content": "The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney.", "contents": "Renal hydrogen ion secretion after release of unilateral ureteral obstruction. The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney."}
{"id": "PMID:10741", "title": "Effects of increased O2 and CO2 on acid secretion by dogfish gastric mucosa in vitro.", "content": "The gastric mucosa of the dogfish (Squalus acanthias), as usually prepared for in vitro chambered experiments, shows a secretory rate (JH) of about 2 mueq/cm2-h, but a potential difference (PD) of zero. Raising PCO2 from 0.05 to 0.1 atm increases JH by 40% and causes the development of a PD of about 2 mV, mucosal surface positive. Increasing PO2 from 0.9 to 1.9 atm in a hyperbaric chamber (at constant PCO2 = 0.1 atm) doubles JH and increases PD to 5 mV. Transepithelial resistance falls by 20% at high PO2. It appears that the dogfish gastric mucosa, like that of the frog, is rate limited by CO2 diffusion into the tissue from the usual 5% mixture and is also rate limited by the usual O2 levels (unlike the frog), presumably due to its thicker structure and higher O2 consumption. The mucosal-positive PD, which is reversed from all other mucosae studied, is readily explained by separate electrogenic H+ and Cl- pumps, but less readily by schemes embodying a neutral HCl pump. It is not yet known whether the hyperbaric conditions are sufficient to ensure O2 sufficiency.", "contents": "Effects of increased O2 and CO2 on acid secretion by dogfish gastric mucosa in vitro. The gastric mucosa of the dogfish (Squalus acanthias), as usually prepared for in vitro chambered experiments, shows a secretory rate (JH) of about 2 mueq/cm2-h, but a potential difference (PD) of zero. Raising PCO2 from 0.05 to 0.1 atm increases JH by 40% and causes the development of a PD of about 2 mV, mucosal surface positive. Increasing PO2 from 0.9 to 1.9 atm in a hyperbaric chamber (at constant PCO2 = 0.1 atm) doubles JH and increases PD to 5 mV. Transepithelial resistance falls by 20% at high PO2. It appears that the dogfish gastric mucosa, like that of the frog, is rate limited by CO2 diffusion into the tissue from the usual 5% mixture and is also rate limited by the usual O2 levels (unlike the frog), presumably due to its thicker structure and higher O2 consumption. The mucosal-positive PD, which is reversed from all other mucosae studied, is readily explained by separate electrogenic H+ and Cl- pumps, but less readily by schemes embodying a neutral HCl pump. It is not yet known whether the hyperbaric conditions are sufficient to ensure O2 sufficiency."}
{"id": "PMID:10742", "title": "Depression and the reintegration phase of acute schizophrenia.", "content": "The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools.", "contents": "Depression and the reintegration phase of acute schizophrenia. The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools."}
{"id": "PMID:10743", "title": "Self-induced depersonalization syndrome.", "content": "The author reports two cases in which depersonalization occurred during the waking consciousness of individuals who had engaged in meditative techniques designed to alter consciousness. Psychiatrists should be aware of this phenomenon, as the number organizations in the \"consciousness movement\" is increasing, and should ask people manifesting depersonalization about any involvement in activities leading to altered states of consciousness. In some cases it might be appropriate to refer such patients to responsible groups that teach altered consciousness by meditation as an egosyntonic desirable state. The author cautions against the use of phenothiazines in cases where depersonalization is a prominent feature.", "contents": "Self-induced depersonalization syndrome. The author reports two cases in which depersonalization occurred during the waking consciousness of individuals who had engaged in meditative techniques designed to alter consciousness. Psychiatrists should be aware of this phenomenon, as the number organizations in the \"consciousness movement\" is increasing, and should ask people manifesting depersonalization about any involvement in activities leading to altered states of consciousness. In some cases it might be appropriate to refer such patients to responsible groups that teach altered consciousness by meditation as an egosyntonic desirable state. The author cautions against the use of phenothiazines in cases where depersonalization is a prominent feature."}
{"id": "PMID:10746", "title": "Generic and trade-name antipsychotic drugs: clinical equivalence.", "content": "The clinical inequivalence of generic versus trade-name drugs has been reported for nonpsychiatric drugs but rarely for psychotropic drugs. Recent expiration of patents on some psychotropic drugs has made the evaluation of the clinical equivalence of generic versus trade-name drugs a matter of interest from methodological, sociopolitical, and economic aspects. The authors discuss these points, with emphasis on methodology, in their report of a double-blind study of the efficacy of chlorpromazine and Thorazine in the treatment of 54 acute schizophrenic patients. An analysis designed to infer the maximum possible advantage of Thorazine over generic chlorpromazine indicated that differences between the two were clinically insignificant.", "contents": "Generic and trade-name antipsychotic drugs: clinical equivalence. The clinical inequivalence of generic versus trade-name drugs has been reported for nonpsychiatric drugs but rarely for psychotropic drugs. Recent expiration of patents on some psychotropic drugs has made the evaluation of the clinical equivalence of generic versus trade-name drugs a matter of interest from methodological, sociopolitical, and economic aspects. The authors discuss these points, with emphasis on methodology, in their report of a double-blind study of the efficacy of chlorpromazine and Thorazine in the treatment of 54 acute schizophrenic patients. An analysis designed to infer the maximum possible advantage of Thorazine over generic chlorpromazine indicated that differences between the two were clinically insignificant."}
{"id": "PMID:10747", "title": "Coffee consumption among psychiatric inpatients.", "content": "Of 135 patients on an acute psychiatric ward, 34 were \"high users\" of coffee. The high users tended to be older, single, and have diagnoses of psychosis. They showed significantly more state anxiety than other patients, but there were no differences in trait anxiety or MMPI scores. Further research is suggested to determine whether high caffeine consumption among inpatients may be related to staff coffee-drinking behavior and/or treatment with anticholinergic drugs.", "contents": "Coffee consumption among psychiatric inpatients. Of 135 patients on an acute psychiatric ward, 34 were \"high users\" of coffee. The high users tended to be older, single, and have diagnoses of psychosis. They showed significantly more state anxiety than other patients, but there were no differences in trait anxiety or MMPI scores. Further research is suggested to determine whether high caffeine consumption among inpatients may be related to staff coffee-drinking behavior and/or treatment with anticholinergic drugs."}
{"id": "PMID:10748", "title": "Catatonialike symptomatology and withdrawal dyskinesias.", "content": "The authors describes a patient who presented catatonialike symptoms and dyskinesias associated with glutethimide discontinuance and antihistamine use. He hypothesizes that altered dopamine metabolism may produce some of the unusual neuropsychiatric characteristics of glutethimide withdrawal. Drug-withdrawal catatonia may be an additional entity in the differential diagnosis of catatonialike states of organic etiology.", "contents": "Catatonialike symptomatology and withdrawal dyskinesias. The authors describes a patient who presented catatonialike symptoms and dyskinesias associated with glutethimide discontinuance and antihistamine use. He hypothesizes that altered dopamine metabolism may produce some of the unusual neuropsychiatric characteristics of glutethimide withdrawal. Drug-withdrawal catatonia may be an additional entity in the differential diagnosis of catatonialike states of organic etiology."}
{"id": "PMID:10751", "title": "Formal presentation at a scientific meeting.", "content": "The giving of a ten minute scientific communication is an art form peculiar to researchers who frequently fail to research the technology required for the performance. Careful selection of the scientific material to be included, the audio-visual aids to support it, and adequate rehearsal before presentation to a critical audience are vital to the success of the presentation.", "contents": "Formal presentation at a scientific meeting. The giving of a ten minute scientific communication is an art form peculiar to researchers who frequently fail to research the technology required for the performance. Careful selection of the scientific material to be included, the audio-visual aids to support it, and adequate rehearsal before presentation to a critical audience are vital to the success of the presentation."}
{"id": "PMID:10752", "title": "Intravenous flunitrazepam as an anesthetic induction agent.", "content": "The effects of the fluorinated benzodiazepine compound flunitrazepam were studied in eighty patients. The drug was administered intravenously in a standard dose of 2 mg, 3 mg, or 4 mg to supplement lumbar epidural analgesia. Induction was smooth and pleasant. The sleep onset time was dose related and exceeded one minute in the majority of patients. Sleep was invariably produced in patients receiving 4 mg but at lower dosage some patients failed to become unconscious. Pain in the arm during injection was a common feature. The respiratory rate was slightly increased, but in two patients apnoea occurred at induction. The cardiovascular system was minimally depressed with a small decrease in systolic blood pressure and pulse rate. Recovery from sleep was slow but sequelae were minimal. The sedative and amnesic properties contributed significantly to the high rate of patient acceptance.", "contents": "Intravenous flunitrazepam as an anesthetic induction agent. The effects of the fluorinated benzodiazepine compound flunitrazepam were studied in eighty patients. The drug was administered intravenously in a standard dose of 2 mg, 3 mg, or 4 mg to supplement lumbar epidural analgesia. Induction was smooth and pleasant. The sleep onset time was dose related and exceeded one minute in the majority of patients. Sleep was invariably produced in patients receiving 4 mg but at lower dosage some patients failed to become unconscious. Pain in the arm during injection was a common feature. The respiratory rate was slightly increased, but in two patients apnoea occurred at induction. The cardiovascular system was minimally depressed with a small decrease in systolic blood pressure and pulse rate. Recovery from sleep was slow but sequelae were minimal. The sedative and amnesic properties contributed significantly to the high rate of patient acceptance."}
{"id": "PMID:10757", "title": "In vitro effects of certain neurohumors on ultrastructural change of the chick embryonic thyroid gland.", "content": "In vitro effects of certain neurohumors, on ultrastructure of 14 days old chick embryonic thyroid gland, has been studied. When the chick embryonic thyroid gland was cultivated in vitro, in the medium containing neurohumors like acetylcholine, adrenaline and histamine for a definite period in a particular sequence and dose, has resulted almost similar ultrastructural changes as seen in the hyperactive thyroid gland.", "contents": "In vitro effects of certain neurohumors on ultrastructural change of the chick embryonic thyroid gland. In vitro effects of certain neurohumors, on ultrastructure of 14 days old chick embryonic thyroid gland, has been studied. When the chick embryonic thyroid gland was cultivated in vitro, in the medium containing neurohumors like acetylcholine, adrenaline and histamine for a definite period in a particular sequence and dose, has resulted almost similar ultrastructural changes as seen in the hyperactive thyroid gland."}
{"id": "PMID:10758", "title": "Histological response of various endocrine glands after administration of certain neurohumors in chicks.", "content": "Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors.", "contents": "Histological response of various endocrine glands after administration of certain neurohumors in chicks. Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors."}
{"id": "PMID:10761", "title": "[Anaphylactic shock to pentothal induction].", "content": "In a patient who had been anaesthetised twice with penthiobarbitone, who had contracted a localised then a generalised eczema, collapse appeared during a third anaesthetic induction, 30 minutes after the injection of penthiobarbitone which was revealed by Shelley's test to be the most positive product.", "contents": "[Anaphylactic shock to pentothal induction]. In a patient who had been anaesthetised twice with penthiobarbitone, who had contracted a localised then a generalised eczema, collapse appeared during a third anaesthetic induction, 30 minutes after the injection of penthiobarbitone which was revealed by Shelley's test to be the most positive product."}
{"id": "PMID:10762", "title": "[Anaphylactoid complications of iodide contrast media in arteriography of the lower extremities during general anesthesia].", "content": "The authors studied the manifestations of intolerance to certain iodide contrast products injected by the arterial route, under general anaesthesia. The study covers 385 arteriographies of the lower limbs which were divided into two groups, depending on whether a cortisone premedication had been administrated or not. In the premedicated group, no incidents were noted. In the other group, 13 p. 100 of subjects had cutaneous manifestations with Radioselectan. General anaesthesia did not avoid the accidents which depend on the nature and the quantity of the product injected. Corticosteroids prevent these reactions.", "contents": "[Anaphylactoid complications of iodide contrast media in arteriography of the lower extremities during general anesthesia]. The authors studied the manifestations of intolerance to certain iodide contrast products injected by the arterial route, under general anaesthesia. The study covers 385 arteriographies of the lower limbs which were divided into two groups, depending on whether a cortisone premedication had been administrated or not. In the premedicated group, no incidents were noted. In the other group, 13 p. 100 of subjects had cutaneous manifestations with Radioselectan. General anaesthesia did not avoid the accidents which depend on the nature and the quantity of the product injected. Corticosteroids prevent these reactions."}
{"id": "PMID:10763", "title": "[Complications of local anesthetics].", "content": "With reference to two personal cases of accidents due to local anaesthetics, the authors deal with the clinical symptomatology of these accidents, whether they be toxic or truly allargic, and look at the treatment.", "contents": "[Complications of local anesthetics]. With reference to two personal cases of accidents due to local anaesthetics, the authors deal with the clinical symptomatology of these accidents, whether they be toxic or truly allargic, and look at the treatment."}
{"id": "PMID:10764", "title": "[Clinical observations of per- and post-anesthetic anaphylactoid complications. Results of an a posteriori survey].", "content": "After enquiry in seven French anaesthetic departments, 66 cases of anaphylactic accidents during and after anaesthesia were grouped together. The following are successively described, the clinical symptomatology, the products incriminated, the treatment and course. The immuno-allergological tests were not always carried out.", "contents": "[Clinical observations of per- and post-anesthetic anaphylactoid complications. Results of an a posteriori survey]. After enquiry in seven French anaesthetic departments, 66 cases of anaphylactic accidents during and after anaesthesia were grouped together. The following are successively described, the clinical symptomatology, the products incriminated, the treatment and course. The immuno-allergological tests were not always carried out."}
{"id": "PMID:10765", "title": "[Bronchial mediators and receptors: current data].", "content": "This is a very precise study of the mechanisms which intervene in bronchial motility. It is apparent that the most important recent acquisitions in the realm of bronchial mediators, over these last 10 years remains: the demonstration in the animal and in man of the duality between adrenergic bronchoconstriction of alpha nature and adrenergic bronchoconstriction of beta-2 nature, the duality of the effects of prostaglandins (PGF2 alpha broncho-constrictive, and PGE2 bronchodilator), and the role of cyclic AMP at the junction of the action of numerous substances which are active on the bronchial musculature.", "contents": "[Bronchial mediators and receptors: current data]. This is a very precise study of the mechanisms which intervene in bronchial motility. It is apparent that the most important recent acquisitions in the realm of bronchial mediators, over these last 10 years remains: the demonstration in the animal and in man of the duality between adrenergic bronchoconstriction of alpha nature and adrenergic bronchoconstriction of beta-2 nature, the duality of the effects of prostaglandins (PGF2 alpha broncho-constrictive, and PGE2 bronchodilator), and the role of cyclic AMP at the junction of the action of numerous substances which are active on the bronchial musculature."}
{"id": "PMID:10766", "title": "[Allergy and anesthesia: environment and psychological factors].", "content": "The assessment of so-called risk \"carriers\" is difficult from the standpoint of true allergy and consideration must be given to the following:- the psychology and environment of the patient to be anaesthesia, with regard to any warning signs. -also, though, the psychology and environment of the anaesthetist; himself alerted in the presence of a presumptive allergy. Such an attitude will lead to more rapid assessment of the true nature of the complication occurring. In most instances, acquired presumptions can only lead to widened prevention. A formal anaesthetic consultation, including a careful history, will aid in the detection of problems. It is also of significant value from a legal standpoint, at the same time ensuring application by the anaesthetist of appropriate therapy as early as possible.", "contents": "[Allergy and anesthesia: environment and psychological factors]. The assessment of so-called risk \"carriers\" is difficult from the standpoint of true allergy and consideration must be given to the following:- the psychology and environment of the patient to be anaesthesia, with regard to any warning signs. -also, though, the psychology and environment of the anaesthetist; himself alerted in the presence of a presumptive allergy. Such an attitude will lead to more rapid assessment of the true nature of the complication occurring. In most instances, acquired presumptions can only lead to widened prevention. A formal anaesthetic consultation, including a careful history, will aid in the detection of problems. It is also of significant value from a legal standpoint, at the same time ensuring application by the anaesthetist of appropriate therapy as early as possible."}
{"id": "PMID:10767", "title": "[Pre-anesthesia survey].", "content": "The pre-anaesthesia enquiry reposes essentially on a detailed interrogation, with respects to the risks of anaphylactic accident. Two types of information must be obtained: the presence of risk factors (related to an allergic background, to the pre-existence of a drug allergy, to a spasmophilic background) on the one hand; knowledge of anaesthetic substances and adjuvants already used, on the other hand.", "contents": "[Pre-anesthesia survey]. The pre-anaesthesia enquiry reposes essentially on a detailed interrogation, with respects to the risks of anaphylactic accident. Two types of information must be obtained: the presence of risk factors (related to an allergic background, to the pre-existence of a drug allergy, to a spasmophilic background) on the one hand; knowledge of anaesthetic substances and adjuvants already used, on the other hand."}
{"id": "PMID:10768", "title": "[What prevents the diagnosis of spasmphilia].", "content": "The frequency of spasmophilia in subjects who had had anaphylactic reactions during anaesthesia (80 p. 100 in our statistics, as opposed to 10 p. 100 in a normal population) must make one consider this condition as a risk factor. It must be looked for in the history, on clinical examination, on the electromyogram, and by laboratory assays. Therapeutic orientations are indicated.", "contents": "[What prevents the diagnosis of spasmphilia]. The frequency of spasmophilia in subjects who had had anaphylactic reactions during anaesthesia (80 p. 100 in our statistics, as opposed to 10 p. 100 in a normal population) must make one consider this condition as a risk factor. It must be looked for in the history, on clinical examination, on the electromyogram, and by laboratory assays. Therapeutic orientations are indicated."}
{"id": "PMID:10769", "title": "[Skin tests for 48/80 and histamine].", "content": "The variability in time of the cutaneous response, resulting from morbid and specially from therapeutic physiological interferences, restrains the credibility of cutaneous allergological investigations. The authors present the first results, established on control population considered as normal, of an approach to cutaneous reactivity by means of a non-specific histamine liberation, induced by a tween: 48/80 coupled with appreciation of the reactivity to histamine injected by the intra-dermal route. The study objectively demonstrates the variability in the response in terms of the doses injected, age, and especially in terms of drug interferences which usually, go in the direction of a hyporeactivity. On the contrary, hyper-reactivity is frequently observed in certain morbid conditions, in particular in spasmophilia. In conclusion, before including the 48/80 and histamine tests in the battery of allergological investigations, it seems indispensable to specify the limits in normal subjects and to better aprehend interferences which modify its expression.", "contents": "[Skin tests for 48/80 and histamine]. The variability in time of the cutaneous response, resulting from morbid and specially from therapeutic physiological interferences, restrains the credibility of cutaneous allergological investigations. The authors present the first results, established on control population considered as normal, of an approach to cutaneous reactivity by means of a non-specific histamine liberation, induced by a tween: 48/80 coupled with appreciation of the reactivity to histamine injected by the intra-dermal route. The study objectively demonstrates the variability in the response in terms of the doses injected, age, and especially in terms of drug interferences which usually, go in the direction of a hyporeactivity. On the contrary, hyper-reactivity is frequently observed in certain morbid conditions, in particular in spasmophilia. In conclusion, before including the 48/80 and histamine tests in the battery of allergological investigations, it seems indispensable to specify the limits in normal subjects and to better aprehend interferences which modify its expression."}
{"id": "PMID:10770", "title": "[Determination of serum IgE].", "content": "After recalling the properties of IgE antibodies responsible for allergic reactions, the author looks at the methods of assay by the techniques of radial immunodiffusion and radio-immunology. The total serum IgE of 13 subjects who had had an anaphylactic accident during anaesthesia, were assayed according to the latter technique. Elevated values were found in patient with an atopic background. The assay of IgE could be of value in the assessment of the allergic risk in anaesthesia.", "contents": "[Determination of serum IgE]. After recalling the properties of IgE antibodies responsible for allergic reactions, the author looks at the methods of assay by the techniques of radial immunodiffusion and radio-immunology. The total serum IgE of 13 subjects who had had an anaphylactic accident during anaesthesia, were assayed according to the latter technique. Elevated values were found in patient with an atopic background. The assay of IgE could be of value in the assessment of the allergic risk in anaesthesia."}
{"id": "PMID:10772", "title": "[2 cases of anaphylactic-type reaction to alphadione (Alfatesine, Althesin, CT 13.41)].", "content": "Two cases of anaphylactic-type reaction to alfadione were referred to our Department for immuno-allergic enquiry. From the clinical standpoint, the pictures obtained were rather similar, dominated by dramatic collapse of abrupt onset associated with an erythemato-oedematous cervico-facial rash, however with a favourable course under respiratory and circulatory emergency resuscitation. The immunological enquiry carried out in both cases did not enable one to attribute the responsibility for the accident to alfadione or to cremophor EL nor to be able to put it down to a direct pharmacological histamine-liberation, or to a specific histamine-liberation due to an antigen-antibody reaction.", "contents": "[2 cases of anaphylactic-type reaction to alphadione (Alfatesine, Althesin, CT 13.41)]. Two cases of anaphylactic-type reaction to alfadione were referred to our Department for immuno-allergic enquiry. From the clinical standpoint, the pictures obtained were rather similar, dominated by dramatic collapse of abrupt onset associated with an erythemato-oedematous cervico-facial rash, however with a favourable course under respiratory and circulatory emergency resuscitation. The immunological enquiry carried out in both cases did not enable one to attribute the responsibility for the accident to alfadione or to cremophor EL nor to be able to put it down to a direct pharmacological histamine-liberation, or to a specific histamine-liberation due to an antigen-antibody reaction."}
{"id": "PMID:10773", "title": "[2 cases of anaphylactic-type reaction related to anesthesia].", "content": "Two cases of anaphylactic shock during anaesthesia are presented, in which the etiology is confirmed by the lymphoblastic transformation test. In one case, the responsability was due to Pentothal, in the other to the combination of Pentothal-succinylcholine.", "contents": "[2 cases of anaphylactic-type reaction related to anesthesia]. Two cases of anaphylactic shock during anaesthesia are presented, in which the etiology is confirmed by the lymphoblastic transformation test. In one case, the responsability was due to Pentothal, in the other to the combination of Pentothal-succinylcholine."}
{"id": "PMID:10774", "title": "[In tolerance reactions to Rheomacrodes. Apropos of 3 cases].", "content": "Three cases of reactions of intolerance to Rheomacrodex were observed during these last four years in our Department, and this led us to attempt to sum up their exact nature and in particular the possibility of an immuno-allergic orgin. From the clinical standpoint, the symptomatology is dominated by the combination of abrupt collapse associated with Quincke's edema in two cases, and with bronchospasm in the third. The course was rapidly favourable under respiratory and circulatory emergency resuscitation. The immuno-allergic enquiry carried out in one case, did not enable one to demonstrate the responsibility of an antigen-antibody reaction. Analysis of the different works appeared on this subject, in particular those of the Swedish school, of W. RICHTER et col., did not enable one to pick out with any certainty the responsibility of an antigen-antibody conflict in the genesis of these reactions.", "contents": "[In tolerance reactions to Rheomacrodes. Apropos of 3 cases]. Three cases of reactions of intolerance to Rheomacrodex were observed during these last four years in our Department, and this led us to attempt to sum up their exact nature and in particular the possibility of an immuno-allergic orgin. From the clinical standpoint, the symptomatology is dominated by the combination of abrupt collapse associated with Quincke's edema in two cases, and with bronchospasm in the third. The course was rapidly favourable under respiratory and circulatory emergency resuscitation. The immuno-allergic enquiry carried out in one case, did not enable one to demonstrate the responsibility of an antigen-antibody reaction. Analysis of the different works appeared on this subject, in particular those of the Swedish school, of W. RICHTER et col., did not enable one to pick out with any certainty the responsibility of an antigen-antibody conflict in the genesis of these reactions."}
{"id": "PMID:10775", "title": "[Does anesthesia have an immunosuppressive effect?].", "content": "Immune depression occurs after general anaesthesia. It is related to depression of serum factors after anesthesia with ether or chloroform, or secondary to depression of antibody-producing cells after anaesthesia with halothane, nitrous oxyde or Pentothal. This immune depression augments proneness to bacterial and viral infection and to malignant disease.", "contents": "[Does anesthesia have an immunosuppressive effect?]. Immune depression occurs after general anaesthesia. It is related to depression of serum factors after anesthesia with ether or chloroform, or secondary to depression of antibody-producing cells after anaesthesia with halothane, nitrous oxyde or Pentothal. This immune depression augments proneness to bacterial and viral infection and to malignant disease."}
{"id": "PMID:10776", "title": "[Does local regional anesthesia exert an immunosuppressive effect?].", "content": "Lignocaine in very high doses exhibits immunodepressant properties in vitro. In vivo, in surgical patients submitted to spinal anaesthesia, lymphocyte transformation is diminished for one week. This inhibition is, however, less marked than after general anaesthesia.", "contents": "[Does local regional anesthesia exert an immunosuppressive effect?]. Lignocaine in very high doses exhibits immunodepressant properties in vitro. In vivo, in surgical patients submitted to spinal anaesthesia, lymphocyte transformation is diminished for one week. This inhibition is, however, less marked than after general anaesthesia."}
{"id": "PMID:10777", "title": "[Diagnosis of drug allergies related to anesthesia and surgery].", "content": "Drug allergies are increasingly common. They may occur in 5-10 p. 100 of patients treated with drugs. From a diagnostic standpoint, the problem is a complex one, many aspects of which are still poorly understood. This is particularly true with regard to the nature of the antigenic determinants and their vectors. Allergic reactions in patients submitted to anaesthesia and surgery represent a very particular case of the situation. A study of the immune status of such patients was undertaken and revealed that T lymphocyte depression, lasting from one to three weeks, often occurs. It is important to take this concept into account when choosing laboratory tests designed to substantiate the diagnosis. Several examples are presented and discussed.", "contents": "[Diagnosis of drug allergies related to anesthesia and surgery]. Drug allergies are increasingly common. They may occur in 5-10 p. 100 of patients treated with drugs. From a diagnostic standpoint, the problem is a complex one, many aspects of which are still poorly understood. This is particularly true with regard to the nature of the antigenic determinants and their vectors. Allergic reactions in patients submitted to anaesthesia and surgery represent a very particular case of the situation. A study of the immune status of such patients was undertaken and revealed that T lymphocyte depression, lasting from one to three weeks, often occurs. It is important to take this concept into account when choosing laboratory tests designed to substantiate the diagnosis. Several examples are presented and discussed."}
{"id": "PMID:10778", "title": "[Immunobiological means of identifying hypersensitivity to anesthetics and adjuvants].", "content": "The diagnosis of hypersensitivity to anesthetics and adjuvants is based chiefly on immunobiological tests which involve:-sensitized lymphocytes; -IgE or IgG antibodies; -sensitized target cells; -determination of chemical mediators. Comparison between these different methods is only possible for techniques involving the sensitized lymphocyte, such as the LTT and EA rosettes for examples, or T.D.B.H. and liberation of histamine. Comparison between the LTT and RAST is difficult, since the first technique investigates the sensitized lymphocyte while the second involves radio-immune antibody assay. An attempt to establish a correlation between these two types of methods is difficult but they can, however, complement each other.", "contents": "[Immunobiological means of identifying hypersensitivity to anesthetics and adjuvants]. The diagnosis of hypersensitivity to anesthetics and adjuvants is based chiefly on immunobiological tests which involve:-sensitized lymphocytes; -IgE or IgG antibodies; -sensitized target cells; -determination of chemical mediators. Comparison between these different methods is only possible for techniques involving the sensitized lymphocyte, such as the LTT and EA rosettes for examples, or T.D.B.H. and liberation of histamine. Comparison between the LTT and RAST is difficult, since the first technique investigates the sensitized lymphocyte while the second involves radio-immune antibody assay. An attempt to establish a correlation between these two types of methods is difficult but they can, however, complement each other."}
{"id": "PMID:10779", "title": "[A study of allergy to local anesthetics using the lymphoblast transformation test].", "content": "The lymphocyte transformation test (LTT) confirms the classical concept that Novocain is three times as potent as Xylocaine as a sensitizing agent. This sensitization to Novocaine is more common in patients with an allergic constitution and in those treated with several drugs. The LTT made it possible to identify the responsible drug, which was not always a local anesthetic, but sometimes Penicillin G and aspirin.", "contents": "[A study of allergy to local anesthetics using the lymphoblast transformation test]. The lymphocyte transformation test (LTT) confirms the classical concept that Novocain is three times as potent as Xylocaine as a sensitizing agent. This sensitization to Novocaine is more common in patients with an allergic constitution and in those treated with several drugs. The LTT made it possible to identify the responsible drug, which was not always a local anesthetic, but sometimes Penicillin G and aspirin."}
{"id": "PMID:10780", "title": "[Allergic characteristics of halothane hepatitis. Apropos of a case report].", "content": "The authors report a case of postoperative jaundice occurring within 30 days in a patient anesthetized three times with halothane. The responsibility of the anesthetic is discussed in view of the positivity of the lymphocyte transformation test and the absence of Australia antigen. It is suggested that this case of hepatitis may be related to a delayed hypersensitivity phenomen.", "contents": "[Allergic characteristics of halothane hepatitis. Apropos of a case report]. The authors report a case of postoperative jaundice occurring within 30 days in a patient anesthetized three times with halothane. The responsibility of the anesthetic is discussed in view of the positivity of the lymphocyte transformation test and the absence of Australia antigen. It is suggested that this case of hepatitis may be related to a delayed hypersensitivity phenomen."}
{"id": "PMID:10781", "title": "[Experimental study of the sensitizing properties of halothane].", "content": "The sensitizing properties of halothane were investigated experimentally in guinea pigs using two different techniques. The first method, derived from that of DRAIZE, included a sensitizing phase in which the product was administered by inhalation, while the second method, derived from that of MAGNUSSON and KLIGMAN, used guinea pigs sensitized to FREUND's adjuvant and which were sensitized to halothane administered subcutaneously. The results obtained in these two series of experiments appeared concordant. They showed that effective sensitization occurred in 60 to 80 p. 100 of the animals treated. This places halothane between level 3 (moderate potency) and level 4 (high potency) on the classical drug scale of \"allergenic potencies\".", "contents": "[Experimental study of the sensitizing properties of halothane]. The sensitizing properties of halothane were investigated experimentally in guinea pigs using two different techniques. The first method, derived from that of DRAIZE, included a sensitizing phase in which the product was administered by inhalation, while the second method, derived from that of MAGNUSSON and KLIGMAN, used guinea pigs sensitized to FREUND's adjuvant and which were sensitized to halothane administered subcutaneously. The results obtained in these two series of experiments appeared concordant. They showed that effective sensitization occurred in 60 to 80 p. 100 of the animals treated. This places halothane between level 3 (moderate potency) and level 4 (high potency) on the classical drug scale of \"allergenic potencies\"."}
{"id": "PMID:10782", "title": "[Experimental study of conjugates of a catabolite common to halothane, enflurane and fluroxene in guinea pigs].", "content": "The authors sensitized guinea pigs to a halothane catabolite, trifluoroacetic acid, combined with guinea pig albumin. They then exposed the animals to halothane. There was no correlation between the presence of humoral and cell-mediated immune reactions obtained with the catabolite and the incidence of liver necrosis.", "contents": "[Experimental study of conjugates of a catabolite common to halothane, enflurane and fluroxene in guinea pigs]. The authors sensitized guinea pigs to a halothane catabolite, trifluoroacetic acid, combined with guinea pig albumin. They then exposed the animals to halothane. There was no correlation between the presence of humoral and cell-mediated immune reactions obtained with the catabolite and the incidence of liver necrosis."}
{"id": "PMID:10783", "title": "[Immunologic study of viral hepatitis].", "content": "The author discusses the various immunological methods used to demonstrate antigen in serum hepatitis. This antigen is made up of three main types of particles: a spherical particle, a tub-like structure and a second larger spherical particle with a hexagonal centre, described by DANE. The centre of DANE's particle is immunologically distinct from its surface. The immune complexes thus formed by antibody links between surface antigens play a major role in extrahepatic manifestations of serum hepatitis. The various subtypes of antigen can be used as a basis for geographical and epidemiological study of the disease. The centre of DANE's particle is considered to be the virus itself. It cannot be cultured with current methods but it can be transmitted to chimpanzees. The antibody reacting with the surface antigen is protective. In conclusion, the author observed that an increase in serum transaminases in anesthetized patients occurred only after halothane. This suggests that liver damage after administration of halothane may be due to a direct effect of the product or its metabolites.", "contents": "[Immunologic study of viral hepatitis]. The author discusses the various immunological methods used to demonstrate antigen in serum hepatitis. This antigen is made up of three main types of particles: a spherical particle, a tub-like structure and a second larger spherical particle with a hexagonal centre, described by DANE. The centre of DANE's particle is immunologically distinct from its surface. The immune complexes thus formed by antibody links between surface antigens play a major role in extrahepatic manifestations of serum hepatitis. The various subtypes of antigen can be used as a basis for geographical and epidemiological study of the disease. The centre of DANE's particle is considered to be the virus itself. It cannot be cultured with current methods but it can be transmitted to chimpanzees. The antibody reacting with the surface antigen is protective. In conclusion, the author observed that an increase in serum transaminases in anesthetized patients occurred only after halothane. This suggests that liver damage after administration of halothane may be due to a direct effect of the product or its metabolites."}
{"id": "PMID:10785", "title": "[Antigenicity of drugs used in anesthesiology].", "content": "The authors studies the factors involved in the antigenicity of the principal medications used in anaesthetics, including general anaesthesia, local anaesthetics and muscle relaxants. Any attempt at establishing a correlation between the chemical properties of these medications and their haptenic power would seem difficult by virtue of the fact that the complications seen in clinical practice are characterised by their rarity. The latter may be explained either on the basis of a low haptenic power of the substances or by the fact of their administration which is rarely repeated after a short time interval. Finally, the difficulties of this correlation are even further increased by the fact that the haptenic power is not always due to the medication itself, but sometimes to one of its metabolites.", "contents": "[Antigenicity of drugs used in anesthesiology]. The authors studies the factors involved in the antigenicity of the principal medications used in anaesthetics, including general anaesthesia, local anaesthetics and muscle relaxants. Any attempt at establishing a correlation between the chemical properties of these medications and their haptenic power would seem difficult by virtue of the fact that the complications seen in clinical practice are characterised by their rarity. The latter may be explained either on the basis of a low haptenic power of the substances or by the fact of their administration which is rarely repeated after a short time interval. Finally, the difficulties of this correlation are even further increased by the fact that the haptenic power is not always due to the medication itself, but sometimes to one of its metabolites."}
{"id": "PMID:10786", "title": "[Technics for the experimental study of delayed hypersensitivity].", "content": "The author reviews the principal experimental methods proposed for the study of the sensitising power of medications. All these methods involve delayed hypersensitivity (Type IV) and fall into the same broad category, with a sensitisation phase, a rest phase and a stimulating phase. A critical review of these various phases is made; together with the interpretation of the results and their significance.", "contents": "[Technics for the experimental study of delayed hypersensitivity]. The author reviews the principal experimental methods proposed for the study of the sensitising power of medications. All these methods involve delayed hypersensitivity (Type IV) and fall into the same broad category, with a sensitisation phase, a rest phase and a stimulating phase. A critical review of these various phases is made; together with the interpretation of the results and their significance."}
{"id": "PMID:10787", "title": "[Biological rhythms and chronopharmacology].", "content": "After defining the various factors of chronobiology (chronophysiology, chronopathology, chronotoxicology and chronopharmacology), the authors describe the various methods available for the study of biological rhythms; which leads to the concept of \"time structure\".", "contents": "[Biological rhythms and chronopharmacology]. After defining the various factors of chronobiology (chronophysiology, chronopathology, chronotoxicology and chronopharmacology), the authors describe the various methods available for the study of biological rhythms; which leads to the concept of \"time structure\"."}
{"id": "PMID:10791", "title": "[Plasma level of the thiocyanate ion in sodium nitroprusside perfusion].", "content": "24 subjects were selected at random out of a group of 80 patients undergoing surgery under a hypotensive anaesthetic technique by means of nitroprusside perfusion; the variation of one of the metabolites, the thiocyanide ion, were assayed. Hypotension was of 30 to 380 minutes duration and mean dosage of 12,44 mg (1,99 mug/kg/min). SCN- assays were performed by means of an original technique, which is described in this publication, before any perfusion of nitroprusside, every 30 minutes during perfusion and 30 and 60 minutes after ending the perfusion. Results show that SCN- concentration is increasing during perfusion but not as much as compared with the toxic concentration. Major increase takes place 30 minutes after starting the perfusion (1,27 10(-4) M/l). Increase slows down then and remains on a plateau level until the end of the perfusion where it decreases. Those results allow to reject a toxicity risk related to an increase of SCN- during nitroprusside perfusion. However, the accidents reported after high dosage of NPS and probably related to cyanogenic ion accumulation combined with lactic acidosis as shown in this publication, led the authors to advise a dosage not over 10 mug/kg/min in a maximum of 2 hours time.", "contents": "[Plasma level of the thiocyanate ion in sodium nitroprusside perfusion]. 24 subjects were selected at random out of a group of 80 patients undergoing surgery under a hypotensive anaesthetic technique by means of nitroprusside perfusion; the variation of one of the metabolites, the thiocyanide ion, were assayed. Hypotension was of 30 to 380 minutes duration and mean dosage of 12,44 mg (1,99 mug/kg/min). SCN- assays were performed by means of an original technique, which is described in this publication, before any perfusion of nitroprusside, every 30 minutes during perfusion and 30 and 60 minutes after ending the perfusion. Results show that SCN- concentration is increasing during perfusion but not as much as compared with the toxic concentration. Major increase takes place 30 minutes after starting the perfusion (1,27 10(-4) M/l). Increase slows down then and remains on a plateau level until the end of the perfusion where it decreases. Those results allow to reject a toxicity risk related to an increase of SCN- during nitroprusside perfusion. However, the accidents reported after high dosage of NPS and probably related to cyanogenic ion accumulation combined with lactic acidosis as shown in this publication, led the authors to advise a dosage not over 10 mug/kg/min in a maximum of 2 hours time."}
{"id": "PMID:10792", "title": "[Electromyography and AH/8165 in man].", "content": "This article concerns the electromyographical study of a synthetic curare derived from Azobis Arylimidazo (1-2a) Pyridinium (AH/8165) with a simultaneous recording of the spontaneous diaphragmatic activity and \"testing\" of the neuro-muscular transmission at the level of a peripheral muscle. This study shows that AH/8165 is a powerful non-depolirizing curarimimetic drug that quickly induces a neuro-muscular block at the level of the diaphragm and the peripheric muscles that can be reversed by anticholinesterasic drugs. Its reaction time is short (about 1 mn). There are importante individual variations in the duration of the neuromuscular blockage. Towards the end of the experience, tetanizing stimulations reveal a muscular fatigability in all the cases. No ill side-effects could be observed upon the cardiovascular system or any side-effects ascribable to a histaminergic mechanism.", "contents": "[Electromyography and AH/8165 in man]. This article concerns the electromyographical study of a synthetic curare derived from Azobis Arylimidazo (1-2a) Pyridinium (AH/8165) with a simultaneous recording of the spontaneous diaphragmatic activity and \"testing\" of the neuro-muscular transmission at the level of a peripheral muscle. This study shows that AH/8165 is a powerful non-depolirizing curarimimetic drug that quickly induces a neuro-muscular block at the level of the diaphragm and the peripheric muscles that can be reversed by anticholinesterasic drugs. Its reaction time is short (about 1 mn). There are importante individual variations in the duration of the neuromuscular blockage. Towards the end of the experience, tetanizing stimulations reveal a muscular fatigability in all the cases. No ill side-effects could be observed upon the cardiovascular system or any side-effects ascribable to a histaminergic mechanism."}
{"id": "PMID:10793", "title": "[Epidurography in the continuous peridural anesthesia technic in geriatric surgery].", "content": "The radiographic opacification of the peridural space was carried out prior to any injection of anaesthetic solution, both in the interest of security and to maximize the chances of success, on a homogeneous series of patients of more than 75 years of age, benefiting from continuous peridural analgesia. The following observations are made: - the direction of the catheter is ascending in 94 p. 100 of the cases, - the frequency of malpositions seems to increase with the lenght of the catheter introduced into the space, - the images obtained by injections of the radio-opaque agent are sufficiently specific to allow verification of the extra-dural situation of the apex of the catheter, - the permeability of the intervertebral foramina is found in 36 p. 100 of the cases, - the unilateral blocks appear to be exceptional, the technical difficulties inherent in the effects of aging on the vertebral system being compensated for by the constant success whenever the peridural space is reached.", "contents": "[Epidurography in the continuous peridural anesthesia technic in geriatric surgery]. The radiographic opacification of the peridural space was carried out prior to any injection of anaesthetic solution, both in the interest of security and to maximize the chances of success, on a homogeneous series of patients of more than 75 years of age, benefiting from continuous peridural analgesia. The following observations are made: - the direction of the catheter is ascending in 94 p. 100 of the cases, - the frequency of malpositions seems to increase with the lenght of the catheter introduced into the space, - the images obtained by injections of the radio-opaque agent are sufficiently specific to allow verification of the extra-dural situation of the apex of the catheter, - the permeability of the intervertebral foramina is found in 36 p. 100 of the cases, - the unilateral blocks appear to be exceptional, the technical difficulties inherent in the effects of aging on the vertebral system being compensated for by the constant success whenever the peridural space is reached."}
{"id": "PMID:10794", "title": "[Involvement or non-involvement of intracranial pressure with arterial pressure].", "content": "In this experiment carried out on dogs, the authors demonstrate with the aid of very expressive illustrations that rapid variations in arterial pressure are accompanied by variations of the intracranial pressure. The latter may be, depending on the case, either in the same direction or inverse, according to the local cerebral vasomotor response accompanying the systemic arterial hypertension.", "contents": "[Involvement or non-involvement of intracranial pressure with arterial pressure]. In this experiment carried out on dogs, the authors demonstrate with the aid of very expressive illustrations that rapid variations in arterial pressure are accompanied by variations of the intracranial pressure. The latter may be, depending on the case, either in the same direction or inverse, according to the local cerebral vasomotor response accompanying the systemic arterial hypertension."}
{"id": "PMID:10795", "title": "[PLACEMENT OF AN INTRACAVITARY PROBE WITH RESPECT TO THE TRANSPORT OF CARDIAC PATIENTS UNDERGOING ELECTROSTIMULATION. Apropos of 11 cases at the Toulouse Emergency Medical Assistance Service].", "content": "In connection with the secondary transportation of cardiac patients, the medicine doctors at the SAMU in Toulouse placed endocavitary probes in 11 patients for purposes of electrosystolic releasing. The subjects exhibited auriculo-ventricular blocks resistant to isoprenaline and accompanied by syncopes. The evacuations were carried out in this fashion without any accident and with no negative effects in 10 out of the 11 cases. In light of this result, the indications and techniques of the process are discussed.", "contents": "[PLACEMENT OF AN INTRACAVITARY PROBE WITH RESPECT TO THE TRANSPORT OF CARDIAC PATIENTS UNDERGOING ELECTROSTIMULATION. Apropos of 11 cases at the Toulouse Emergency Medical Assistance Service]. In connection with the secondary transportation of cardiac patients, the medicine doctors at the SAMU in Toulouse placed endocavitary probes in 11 patients for purposes of electrosystolic releasing. The subjects exhibited auriculo-ventricular blocks resistant to isoprenaline and accompanied by syncopes. The evacuations were carried out in this fashion without any accident and with no negative effects in 10 out of the 11 cases. In light of this result, the indications and techniques of the process are discussed."}
{"id": "PMID:10796", "title": "[Amiodarone hydrochloride and anesthesia in heart surgery. Use of an injectable form in the correction of peroperative rhythm disorders].", "content": "The amiodarone is studied in the context of cardiac surgery to evaluate its anti-arrythmic properties in its injectable form and possible interference with the anaesthetic drugs. Two groups of patients were established: - the first group of 10 patients received the amiodarone per-os in the immediate pre-operative period, - the second group of 19 patients received injectable amiodarone either by direct intraveinous injection at a dose of 5 mg/kg or in I.V. drip for rhytmic irregulatities during surgery. The anti-arrythmic property of the product is confirmed. No incompatibility with the anaesthetics employed (neuroleptanalgesia) was observed. Howerer, a potentialization of the sympatholytic alpha-effects by the anaesthesia is observed. The fall in arterial pressure, when it is measureable, is of the order of a third of the initial value, with a return to the previous level within about ten minutes.", "contents": "[Amiodarone hydrochloride and anesthesia in heart surgery. Use of an injectable form in the correction of peroperative rhythm disorders]. The amiodarone is studied in the context of cardiac surgery to evaluate its anti-arrythmic properties in its injectable form and possible interference with the anaesthetic drugs. Two groups of patients were established: - the first group of 10 patients received the amiodarone per-os in the immediate pre-operative period, - the second group of 19 patients received injectable amiodarone either by direct intraveinous injection at a dose of 5 mg/kg or in I.V. drip for rhytmic irregulatities during surgery. The anti-arrythmic property of the product is confirmed. No incompatibility with the anaesthetics employed (neuroleptanalgesia) was observed. Howerer, a potentialization of the sympatholytic alpha-effects by the anaesthesia is observed. The fall in arterial pressure, when it is measureable, is of the order of a third of the initial value, with a return to the previous level within about ten minutes."}
{"id": "PMID:10797", "title": "[Prevention of stress ulcer by vitamin A. Experimental study in rats].", "content": "71 male rats (Whitstar strain) are submitted to restraint. 37 of them were receiving twice an injection of 10 000 I.U. of vitamin A in order to protect them against the occurence of stress ulcer. Untreated animals are used as controls. Incidence of obtained ulcer is compared with the variation of vitamin A serum concentration, classicaly decreased in stress. Analysis of individual results shows that, if parenteral administration was followed either by restitution of the initial serum concentration, or by its increase, the treatment was efficient in 64 p. 100 of the cases.", "contents": "[Prevention of stress ulcer by vitamin A. Experimental study in rats]. 71 male rats (Whitstar strain) are submitted to restraint. 37 of them were receiving twice an injection of 10 000 I.U. of vitamin A in order to protect them against the occurence of stress ulcer. Untreated animals are used as controls. Incidence of obtained ulcer is compared with the variation of vitamin A serum concentration, classicaly decreased in stress. Analysis of individual results shows that, if parenteral administration was followed either by restitution of the initial serum concentration, or by its increase, the treatment was efficient in 64 p. 100 of the cases."}
{"id": "PMID:10798", "title": "[Stress ulcer and acute postoperative renal insufficiency. An attempt at preventive treatment with Solcoseryl and proglumide].", "content": "The study grouped 68 patients treated for severe post-operative or post-traumatic renal insufficiency, having survived over 7 days after being admitted into the Reanimation Department. A group of 32 patients were given systematic preventive treatment for nervous ulcers witch Solcoseryl and Proglumide. A control group of 36 patients received no specific treatment. Nervous ulcerations (showing up in gastrocopy) are found in three patients in the group receiving treatment, as compared with seven in the control group. This preventive treatment appears to be of interest, especially as other local or neuroleptic treatments are difficult to use in the group of patients concerned here.", "contents": "[Stress ulcer and acute postoperative renal insufficiency. An attempt at preventive treatment with Solcoseryl and proglumide]. The study grouped 68 patients treated for severe post-operative or post-traumatic renal insufficiency, having survived over 7 days after being admitted into the Reanimation Department. A group of 32 patients were given systematic preventive treatment for nervous ulcers witch Solcoseryl and Proglumide. A control group of 36 patients received no specific treatment. Nervous ulcerations (showing up in gastrocopy) are found in three patients in the group receiving treatment, as compared with seven in the control group. This preventive treatment appears to be of interest, especially as other local or neuroleptic treatments are difficult to use in the group of patients concerned here."}
{"id": "PMID:10799", "title": "[Clinical evaluation of Triv\u00e9 1000 in surgery].", "content": "Trials with Trive 1000 allow to confirm its perfect tolerance and its real interest in N sparing effect provided a minimum of 1500 ml, or even better 2000 ml are perfused with an adequate caloric carboyhdrate complement. However, in severe cases such as septicemia, one may expect a positive N balance only with much more important supply of N and calories. Since there is almost no change in parameters refleting fat metabolism, one may suppose a normal utilisation of injected fat.", "contents": "[Clinical evaluation of Triv\u00e9 1000 in surgery]. Trials with Trive 1000 allow to confirm its perfect tolerance and its real interest in N sparing effect provided a minimum of 1500 ml, or even better 2000 ml are perfused with an adequate caloric carboyhdrate complement. However, in severe cases such as septicemia, one may expect a positive N balance only with much more important supply of N and calories. Since there is almost no change in parameters refleting fat metabolism, one may suppose a normal utilisation of injected fat."}
{"id": "PMID:10801", "title": "[Technics and indications of general anesthesia for tonsillectomy and adenoidectomy. Apropos of an experience using anesthetic perfusion and cold loop technic].", "content": "The authors present the results of an enquiry carried out in University and regional hospitals in France and recall the interest of general anaesthesia with tracheal intubation during tonsillectomy. This makes possible, even in young children, the use of the technique of cold loop dissection. Its main advantage is in the absolute control of the airways which permits the operator to carry out careful hemostasis. Propanidide used in perfusion, allows these patients to wake up rapidly and the awakening is of good quality; this is essential in this type of operation.", "contents": "[Technics and indications of general anesthesia for tonsillectomy and adenoidectomy. Apropos of an experience using anesthetic perfusion and cold loop technic]. The authors present the results of an enquiry carried out in University and regional hospitals in France and recall the interest of general anaesthesia with tracheal intubation during tonsillectomy. This makes possible, even in young children, the use of the technique of cold loop dissection. Its main advantage is in the absolute control of the airways which permits the operator to carry out careful hemostasis. Propanidide used in perfusion, allows these patients to wake up rapidly and the awakening is of good quality; this is essential in this type of operation."}
{"id": "PMID:10802", "title": "[General anesthesia for multiple dental extractions].", "content": "Between 1970 and 1975, 528 sessions of teeth extractions were carried out under general anaesthesia at the Ambroise Par\u00e9 Hospital in Boulogne. The distribution was as follows: -70 multiple dental extractions in cardiac patients, mostly sent up by cardiology units outside the establishment. -458 multiple dental extractions for orthodontic treatment, germectomies, removal of included or supernumerary teeth, contra-indication or refusal of local anaesthetic. Since 1972, all patients for whom a surgical decision was considered were examined at the Anaesthetic out-patients and the advantages appear obvious. The type of premedication, the choice of the anesthetic technique were classical in the vast majority of cases and, in particular, intubation was carried out as a routine.", "contents": "[General anesthesia for multiple dental extractions]. Between 1970 and 1975, 528 sessions of teeth extractions were carried out under general anaesthesia at the Ambroise Par\u00e9 Hospital in Boulogne. The distribution was as follows: -70 multiple dental extractions in cardiac patients, mostly sent up by cardiology units outside the establishment. -458 multiple dental extractions for orthodontic treatment, germectomies, removal of included or supernumerary teeth, contra-indication or refusal of local anaesthetic. Since 1972, all patients for whom a surgical decision was considered were examined at the Anaesthetic out-patients and the advantages appear obvious. The type of premedication, the choice of the anesthetic technique were classical in the vast majority of cases and, in particular, intubation was carried out as a routine."}
{"id": "PMID:10803", "title": "[General anesthesia in major cancer surgery of the upper respiratory and digestive tracts. Significance of a fentanyl-thiamine combination].", "content": "Synaptanalgesia uses a polysynaptic inhibitor: thiamine and a powerful analgesic drug with or without nitrous oxide. This type of vigil or sub-vigil anesthesia used in major cancer surgery of the upper digestive tract and the airway, permits one to obtain: -efficacious protection of the autonomic nervous system, in spite of manipulations of highly reflexogenic areas, -a marked reduction in bleeding. The technique used is derived from that of other authors: DE CASTRO, MUNDELEER, VALENI, MAZZONI, GASPARETTO, adapting it to this type of surgery and attempting to simplify it.", "contents": "[General anesthesia in major cancer surgery of the upper respiratory and digestive tracts. Significance of a fentanyl-thiamine combination]. Synaptanalgesia uses a polysynaptic inhibitor: thiamine and a powerful analgesic drug with or without nitrous oxide. This type of vigil or sub-vigil anesthesia used in major cancer surgery of the upper digestive tract and the airway, permits one to obtain: -efficacious protection of the autonomic nervous system, in spite of manipulations of highly reflexogenic areas, -a marked reduction in bleeding. The technique used is derived from that of other authors: DE CASTRO, MUNDELEER, VALENI, MAZZONI, GASPARETTO, adapting it to this type of surgery and attempting to simplify it."}
{"id": "PMID:10804", "title": "[Current aspects of ambulatory anesthesia for otorhinolaryngologic and stomatologic surgery in France].", "content": "Ambulatory anaesthesia is becoming more popular in France for several reasons: -for humanitory reasons and greater comfort, -for reasons of economy in hospital, -professional responsibility and insurance. This change has been made possible by: -techniques of anaesthesia using drugs which are eliminated rapidly without any rebound phenomenon, -medical attitudes, such as prior examination of the patient by an anesthetist; this is much better than a rapid examination at night or in the morning on admission of the patient, thus precise control of awakening by tests of psychomotor activity. -changes in hospital structure, e.g. post-anaesthetic awakening wards with specialised personnel. Anonymous questionnaires were sent out to O.R.L. surgeons and French oral surgeons, we received 38.5% replies: -51.75% never used ambulatory anaesthesia, -48.25% used ambulatory anaesthesia almost always in hospital with a recovery room and anaesthetic consultation. Admission to hospital for one day seems rarer. It thus appears that ambulatory anaesthesia is becoming common in France and that more than 50% of surgeons remain opposed to this technique.", "contents": "[Current aspects of ambulatory anesthesia for otorhinolaryngologic and stomatologic surgery in France]. Ambulatory anaesthesia is becoming more popular in France for several reasons: -for humanitory reasons and greater comfort, -for reasons of economy in hospital, -professional responsibility and insurance. This change has been made possible by: -techniques of anaesthesia using drugs which are eliminated rapidly without any rebound phenomenon, -medical attitudes, such as prior examination of the patient by an anesthetist; this is much better than a rapid examination at night or in the morning on admission of the patient, thus precise control of awakening by tests of psychomotor activity. -changes in hospital structure, e.g. post-anaesthetic awakening wards with specialised personnel. Anonymous questionnaires were sent out to O.R.L. surgeons and French oral surgeons, we received 38.5% replies: -51.75% never used ambulatory anaesthesia, -48.25% used ambulatory anaesthesia almost always in hospital with a recovery room and anaesthetic consultation. Admission to hospital for one day seems rarer. It thus appears that ambulatory anaesthesia is becoming common in France and that more than 50% of surgeons remain opposed to this technique."}
{"id": "PMID:10805", "title": "[Trials of controlled hypotension with sodium nitroprusside in ORL surgery. Resistance and tachyphylaxis].", "content": "Sodium nitropusside has been used to lower blood pressure during surgical operations on the ear, nose and throat when an operative field without bleeding was desired, e.g. surgery of the inner ear under microscope in particular. In our experience, with the preparation used, sodium nitropusside proved to be a powerful hypotensive agent, the effect of which comes on early but it is difficult to use owing to frequent tachyphylaxis, the possible causes of which are considered. No undesirable side-effects were noted on the main functions. From this limited personal experience, the efficacy of this technique of per-operative hypotension did not appear greater in the surgical field under consideration to those of the anaesthetic techniques used commonly, e.g. neuroleptanalgesia under artificial ventilation, which proved sufficient for reduction in operative bleeding and which had already caused the authors to abandon, some time ago, the use of hypotensive ganglioplegic drugs.", "contents": "[Trials of controlled hypotension with sodium nitroprusside in ORL surgery. Resistance and tachyphylaxis]. Sodium nitropusside has been used to lower blood pressure during surgical operations on the ear, nose and throat when an operative field without bleeding was desired, e.g. surgery of the inner ear under microscope in particular. In our experience, with the preparation used, sodium nitropusside proved to be a powerful hypotensive agent, the effect of which comes on early but it is difficult to use owing to frequent tachyphylaxis, the possible causes of which are considered. No undesirable side-effects were noted on the main functions. From this limited personal experience, the efficacy of this technique of per-operative hypotension did not appear greater in the surgical field under consideration to those of the anaesthetic techniques used commonly, e.g. neuroleptanalgesia under artificial ventilation, which proved sufficient for reduction in operative bleeding and which had already caused the authors to abandon, some time ago, the use of hypotensive ganglioplegic drugs."}
{"id": "PMID:10807", "title": "[Use of ventilation by oxygen injection in laryngeal microsurgery].", "content": "Thirty patients with a laryngeal polyp or other tumour, were operated on under the microscope. During the operation, which lasted from 10 to 30 minutes, ventilation was ensured by injection of oxygen at 3 to 4 atmospheric pressures through a naso-tracheal catheter. Anaesthesia was obtained by an association of propanidide, small doses of analgesic and succinycholine, constant rate syringes were used for maintenance of narcosis and curarisation. In 23 patients, blood gases were analysed at various stages of the operation permitting one to assess the quality of the ventilation carried out. In a few patients, it was also possible to record pressure curves in the trachea. The results were excellent, both concerning the quality of the ventilation and that of the anaesthesia together with the operative conditions. After recalling the main characteristics of this mode of ventilation which uses Venturi's principle, the authors expose the other methods which are variants compared with their technique of use of this procedure for laryngeal micro-surgery.", "contents": "[Use of ventilation by oxygen injection in laryngeal microsurgery]. Thirty patients with a laryngeal polyp or other tumour, were operated on under the microscope. During the operation, which lasted from 10 to 30 minutes, ventilation was ensured by injection of oxygen at 3 to 4 atmospheric pressures through a naso-tracheal catheter. Anaesthesia was obtained by an association of propanidide, small doses of analgesic and succinycholine, constant rate syringes were used for maintenance of narcosis and curarisation. In 23 patients, blood gases were analysed at various stages of the operation permitting one to assess the quality of the ventilation carried out. In a few patients, it was also possible to record pressure curves in the trachea. The results were excellent, both concerning the quality of the ventilation and that of the anaesthesia together with the operative conditions. After recalling the main characteristics of this mode of ventilation which uses Venturi's principle, the authors expose the other methods which are variants compared with their technique of use of this procedure for laryngeal micro-surgery."}
{"id": "PMID:10808", "title": "[Significance of Alfatesine in anesthesia for multiple dental extractions before major cardiac surgery].", "content": "This technique of anaesthesia used for oral surgical operations such as, multiple dental extractions, apical resection, carried out in cardiac patients before major cardiac surgery under extra-corporeal circulation, for insertion of valvular prostheses or aorto-coronary by-pass operations, has passed by various stages. The present technique associating phenoperidine-alfatesine-suxame-thonium-N2o-o2, was used in the last 58 cases. It presents a certain number of advantages compared with previous techniques: -very stable level of anaesthesia whatever the duration of the operation, -satisfactory cardio-vascular stability, -almost constant absence of hypo-excitability of the myocardium even in patients in poor cardiac condition before the operation with uninterrupted treatment with digitalis and diuretics, -good quality of awakening.", "contents": "[Significance of Alfatesine in anesthesia for multiple dental extractions before major cardiac surgery]. This technique of anaesthesia used for oral surgical operations such as, multiple dental extractions, apical resection, carried out in cardiac patients before major cardiac surgery under extra-corporeal circulation, for insertion of valvular prostheses or aorto-coronary by-pass operations, has passed by various stages. The present technique associating phenoperidine-alfatesine-suxame-thonium-N2o-o2, was used in the last 58 cases. It presents a certain number of advantages compared with previous techniques: -very stable level of anaesthesia whatever the duration of the operation, -satisfactory cardio-vascular stability, -almost constant absence of hypo-excitability of the myocardium even in patients in poor cardiac condition before the operation with uninterrupted treatment with digitalis and diuretics, -good quality of awakening."}
{"id": "PMID:10809", "title": "[Treatment of respiratory distress caused by laryngeal obstruction].", "content": "Respiratory distress due to laryngeal obstruction produces a more or less dramatic syndrome depending on the cause of the obstruction and its evolution in time. Treatment should be immediate in order to avoid death or cerebral and cardiac sequelae. It consists, above all, of restoring the patency of the respiratory tract, the short-circuit obtained by intubation or tracheotomy should, in no case, leave any laryngeal sequelae. The authors present their personal series based on a study of respiratory distress due to laryngeal obstruction in the child. These observations were obtained from a large series of 480 cases of laryngeal dyspnea observed over the last 5 years on the E.N.T. unit of the Edouard Herriot Hospital in Lyons. They contrast a very small number of sub-glottic laryngitis cases requiring intubation or tracheotomy to a very large number of cases of subglottic laryngitis, even with respiratory distress, which recovered with well designed medical treatment. Foreign bodies, of which they report eleven cases, all required emergency surgery. They emphasize the severity of this cause. As far as papillomas and angiomas are concerned, they require emergency treatment, either straightaway or after a trial of medical treatment.", "contents": "[Treatment of respiratory distress caused by laryngeal obstruction]. Respiratory distress due to laryngeal obstruction produces a more or less dramatic syndrome depending on the cause of the obstruction and its evolution in time. Treatment should be immediate in order to avoid death or cerebral and cardiac sequelae. It consists, above all, of restoring the patency of the respiratory tract, the short-circuit obtained by intubation or tracheotomy should, in no case, leave any laryngeal sequelae. The authors present their personal series based on a study of respiratory distress due to laryngeal obstruction in the child. These observations were obtained from a large series of 480 cases of laryngeal dyspnea observed over the last 5 years on the E.N.T. unit of the Edouard Herriot Hospital in Lyons. They contrast a very small number of sub-glottic laryngitis cases requiring intubation or tracheotomy to a very large number of cases of subglottic laryngitis, even with respiratory distress, which recovered with well designed medical treatment. Foreign bodies, of which they report eleven cases, all required emergency surgery. They emphasize the severity of this cause. As far as papillomas and angiomas are concerned, they require emergency treatment, either straightaway or after a trial of medical treatment."}
{"id": "PMID:10810", "title": "[Anesthesia and resuscitation in emergency maxillofacial surgery].", "content": "A series of 290 cases of maxillo facial trauma permitted the authors to draw up the indications for resuscitation and surgery. Restoration of the permeability of the airways is most often obtained by oral intubation under non-depressor pharmcological agents. The difficulties encountered during intubation were usually linked to pain, but sometimes had a mainly mechanical origin, particularly during zygomatic and malar bone fractures. Tracheotomy was exceptional. Hemorrhage was often the major obstacle and, in certain cases, could only be controlled by immobilisation of the fragments. The anaesthetic technique is very similar to that used in neurosurgery.", "contents": "[Anesthesia and resuscitation in emergency maxillofacial surgery]. A series of 290 cases of maxillo facial trauma permitted the authors to draw up the indications for resuscitation and surgery. Restoration of the permeability of the airways is most often obtained by oral intubation under non-depressor pharmcological agents. The difficulties encountered during intubation were usually linked to pain, but sometimes had a mainly mechanical origin, particularly during zygomatic and malar bone fractures. Tracheotomy was exceptional. Hemorrhage was often the major obstacle and, in certain cases, could only be controlled by immobilisation of the fragments. The anaesthetic technique is very similar to that used in neurosurgery."}
{"id": "PMID:10811", "title": "[Anesthesia and pre- and postoperative resuscitation in massive maxillofacial destruction].", "content": "Severe facial injuries are becoming more and more common, -either facial injuries alone or associated with other injuries, -or facial deformities due to cancer which has required radical surgical operation. The authors analyse the cases of 26 patients with trauma and 24 with neoplastic radical surgical modifications. In the first group, pre-operative resuscitation is often an emergency, e.g. tracheotomy to restore or maintain vital respiratory functions. In the second group, the patients are often elderly and undernourished and they require intensive care before operation. In both groups there are common problems: -feeding by gastric catheter is generally required, -many re-operations with their problems: -avoid nutritional disorders, -and avoid morphine addiction.", "contents": "[Anesthesia and pre- and postoperative resuscitation in massive maxillofacial destruction]. Severe facial injuries are becoming more and more common, -either facial injuries alone or associated with other injuries, -or facial deformities due to cancer which has required radical surgical operation. The authors analyse the cases of 26 patients with trauma and 24 with neoplastic radical surgical modifications. In the first group, pre-operative resuscitation is often an emergency, e.g. tracheotomy to restore or maintain vital respiratory functions. In the second group, the patients are often elderly and undernourished and they require intensive care before operation. In both groups there are common problems: -feeding by gastric catheter is generally required, -many re-operations with their problems: -avoid nutritional disorders, -and avoid morphine addiction."}
{"id": "PMID:10812", "title": "[Massive facial destruction. Management, resuscitation, anesthesia, surgery (experience at the Henri-Mondor University Hospital Center)].", "content": "Anaylsing 67 cases of facial injury treated at the Henri Mondor Hospital in Cr\u00e9teil, the authors consider the various problems raised by these injured patients. -first aid, -methods of protection of the airway, -surgical management, -anaesthetic management and resuscitation, -problems of post-operative supervision, -methods of feeding. Owing to the localisation of these lesions, and the surgical methods, these are high risk injured patients who raise complex problems in the pre, per and post-operative periods, dominated by maintenance of the permeability of the airway. A specialised multidisciplinary team ensures coordination of the various acts.", "contents": "[Massive facial destruction. Management, resuscitation, anesthesia, surgery (experience at the Henri-Mondor University Hospital Center)]. Anaylsing 67 cases of facial injury treated at the Henri Mondor Hospital in Cr\u00e9teil, the authors consider the various problems raised by these injured patients. -first aid, -methods of protection of the airway, -surgical management, -anaesthetic management and resuscitation, -problems of post-operative supervision, -methods of feeding. Owing to the localisation of these lesions, and the surgical methods, these are high risk injured patients who raise complex problems in the pre, per and post-operative periods, dominated by maintenance of the permeability of the airway. A specialised multidisciplinary team ensures coordination of the various acts."}
{"id": "PMID:10813", "title": "[Problems presented by closed laryngeal-tracheal injuries].", "content": "The authors consider the problems raised by severe closed laryngotracheal trauma and report 4 cases. -the immediate tisk to life is due to direct involvement of the respiratory tract requiring emergency measures including cardiorespiratory resuscitation in cases of acute asphyxia. -the origin of the initial respiratory distress, if not obvious from the start, may be suspected in view of the difficulties or impossibility of tracheal intubation, which is also liable to aggravate lesions due to trauma. It is one of these rare cases of resuscitation where emergency tracheotomy is essential. It permits also early, precise surgical exploration. -in cases of fracture of the larynx, a wound of the trachea or rupture and separation of the trachea, the reconstruction must be constructiononstruction must be considered within the first 48 hours. Provision of food and resting of the larynx may be conciliated by installing an esophageal catheter or performing a gastrostomy. Benign trauma, such as contusion or laryngeal commotion, requires close supervision association with medical treatment designed to prevent the onset of lesional oedema.", "contents": "[Problems presented by closed laryngeal-tracheal injuries]. The authors consider the problems raised by severe closed laryngotracheal trauma and report 4 cases. -the immediate tisk to life is due to direct involvement of the respiratory tract requiring emergency measures including cardiorespiratory resuscitation in cases of acute asphyxia. -the origin of the initial respiratory distress, if not obvious from the start, may be suspected in view of the difficulties or impossibility of tracheal intubation, which is also liable to aggravate lesions due to trauma. It is one of these rare cases of resuscitation where emergency tracheotomy is essential. It permits also early, precise surgical exploration. -in cases of fracture of the larynx, a wound of the trachea or rupture and separation of the trachea, the reconstruction must be constructiononstruction must be considered within the first 48 hours. Provision of food and resting of the larynx may be conciliated by installing an esophageal catheter or performing a gastrostomy. Benign trauma, such as contusion or laryngeal commotion, requires close supervision association with medical treatment designed to prevent the onset of lesional oedema."}
{"id": "PMID:10814", "title": "[Laryngeo-tracheal contusion caused by a seat belt].", "content": "The authors report cases of laryngo-tracheal rupture due to seat belts. They analyse the mechanisms, the clinical and radiological signs of these lesions. Although these lesions are rare, they should be recognised by medical teams when called to treat injured patients. It is, in fact, at this level that emergency treatment must be carried out, although difficult, this alone permits one to save a certain number of injured patients from asphyxia.", "contents": "[Laryngeo-tracheal contusion caused by a seat belt]. The authors report cases of laryngo-tracheal rupture due to seat belts. They analyse the mechanisms, the clinical and radiological signs of these lesions. Although these lesions are rare, they should be recognised by medical teams when called to treat injured patients. It is, in fact, at this level that emergency treatment must be carried out, although difficult, this alone permits one to save a certain number of injured patients from asphyxia."}
{"id": "PMID:10815", "title": "[Problems presented to the surgeon, anesthetist and resuscitation personnel by fractures of the malar bone (study of 100 cases)].", "content": "The authors emphasize the difficulties encountered with fractures of the zygomatic bone, both from the technical operative points of view and conditions of anaesthesia and intensive care. They distinguish in both fields, the so-called simple zygomatic fractures from fractures associated with multiple injuries of the face or skull. After recalling the surgical techniques, they consider routine management, from diagnosis to recovery from the anaesthetic, emphasizing the problem of the time of the operation, of the method ensuring freedom of the airways and anaesthetic indications used together with problems of intensive care.", "contents": "[Problems presented to the surgeon, anesthetist and resuscitation personnel by fractures of the malar bone (study of 100 cases)]. The authors emphasize the difficulties encountered with fractures of the zygomatic bone, both from the technical operative points of view and conditions of anaesthesia and intensive care. They distinguish in both fields, the so-called simple zygomatic fractures from fractures associated with multiple injuries of the face or skull. After recalling the surgical techniques, they consider routine management, from diagnosis to recovery from the anaesthetic, emphasizing the problem of the time of the operation, of the method ensuring freedom of the airways and anaesthetic indications used together with problems of intensive care."}
{"id": "PMID:10816", "title": "[Surgery of cancer of the larynx. The patient in the pre-, per-, and postoperative period].", "content": "Surgery of tumours of the larynx requires two main types of operation: -Extensive laryngeal surgery including: -the full pre-operative assessment and preparation of the patient's general condition which is always poor, e.g. due to alcoholism or respiratory failure. -variable techniques, adapted to the lesion, for the control of the patency of the upper airway. -operative risks, such as: reventilation shock, reflex cardiac arrest, disorders of cardiac rythm and gas embolism. -Its complications: -may be immediate and poorly specific, especially respiratory, neurological and infective. -secondary and more specific e.g. Pharyngostoma, and tracheal stenosis. -late complications due to spread of a malignant process. -Laryngeal surgery limited to one vocal cord for which local anaesthetic, improved by neuroleptanalgesia, such as Diethazine-Diparcol, best meets the surgeon and the interest of the patient.", "contents": "[Surgery of cancer of the larynx. The patient in the pre-, per-, and postoperative period]. Surgery of tumours of the larynx requires two main types of operation: -Extensive laryngeal surgery including: -the full pre-operative assessment and preparation of the patient's general condition which is always poor, e.g. due to alcoholism or respiratory failure. -variable techniques, adapted to the lesion, for the control of the patency of the upper airway. -operative risks, such as: reventilation shock, reflex cardiac arrest, disorders of cardiac rythm and gas embolism. -Its complications: -may be immediate and poorly specific, especially respiratory, neurological and infective. -secondary and more specific e.g. Pharyngostoma, and tracheal stenosis. -late complications due to spread of a malignant process. -Laryngeal surgery limited to one vocal cord for which local anaesthetic, improved by neuroleptanalgesia, such as Diethazine-Diparcol, best meets the surgeon and the interest of the patient."}
{"id": "PMID:10817", "title": "[Personal experience with anesthesia of ambulatory patients operated on in odontostomatological offices].", "content": "The authors report their experience of anaesthesia of ambulatory patients operated on in dental surgeries; the authors review safety factors, specially, choice of material, drugs and techniques which seem to them essential. They expose in detail their personal techniques, in particular, nasotracheal intubation and open circuit, association of a powerful analgesic drug with a short duration of activity and a mild antiemetic neuroleptic drug completed by inhalation of a mixture of Ethrane and oxygen. The various problems which may occur are considered together with their solutions.", "contents": "[Personal experience with anesthesia of ambulatory patients operated on in odontostomatological offices]. The authors report their experience of anaesthesia of ambulatory patients operated on in dental surgeries; the authors review safety factors, specially, choice of material, drugs and techniques which seem to them essential. They expose in detail their personal techniques, in particular, nasotracheal intubation and open circuit, association of a powerful analgesic drug with a short duration of activity and a mild antiemetic neuroleptic drug completed by inhalation of a mixture of Ethrane and oxygen. The various problems which may occur are considered together with their solutions."}
{"id": "PMID:10818", "title": "[CT 1341 in continuous administration in 75 cases of prolonged general anesthesia in odontostomatology (constant flow assured by a double-lumen venous catheter and electric perfuser)].", "content": "The authors used during 75 prolonged general anaesthesia in maxillo-facial surgery CT. 1341 (Alfatesine) administered pure at constant flow rate through a double lumen venous cannula and electric perfuser. Four series of patients were thus distinguished depending on their use or not of N2O as the only analgesic and of gallamine. We do not agree with the classical assertion that CT. 1341 has a cumulative effect on some EEG results. The technique is quite inocuous and the authors propose a technique using CT. 1341 at a dose of 0.1 ml/kg for induction of anaesthesia with, later, 1 mg/kg of gallamine. Under a mixture of oxygen and nitrous oxide at 60 p. 100, the maintenance dose advised in 6.17 microliters per kilo, per minute of CT. 1341.", "contents": "[CT 1341 in continuous administration in 75 cases of prolonged general anesthesia in odontostomatology (constant flow assured by a double-lumen venous catheter and electric perfuser)]. The authors used during 75 prolonged general anaesthesia in maxillo-facial surgery CT. 1341 (Alfatesine) administered pure at constant flow rate through a double lumen venous cannula and electric perfuser. Four series of patients were thus distinguished depending on their use or not of N2O as the only analgesic and of gallamine. We do not agree with the classical assertion that CT. 1341 has a cumulative effect on some EEG results. The technique is quite inocuous and the authors propose a technique using CT. 1341 at a dose of 0.1 ml/kg for induction of anaesthesia with, later, 1 mg/kg of gallamine. Under a mixture of oxygen and nitrous oxide at 60 p. 100, the maintenance dose advised in 6.17 microliters per kilo, per minute of CT. 1341."}
{"id": "PMID:10819", "title": "[Laryngo-tracheal injuries in hangings (apropos of 359 cases)].", "content": "Hanging is a relatively frequent method of suicide, and strangulation (accidental or volontary) may cause direct laryngeal or tracheal trauma and various lesions which may express themselves clinically either: -early, was severe from the start, e.g. fracture of the larynx, with major ventilatory distress, -or delayed, simple trauma without fracture, becoming manifest only after a few hours with severe dyspnea. In any case, early and late complications of these traumas require, even when they are apparently benign, admission to hospital on a specialised unit able to carry out rapidly respiratory intensive care.", "contents": "[Laryngo-tracheal injuries in hangings (apropos of 359 cases)]. Hanging is a relatively frequent method of suicide, and strangulation (accidental or volontary) may cause direct laryngeal or tracheal trauma and various lesions which may express themselves clinically either: -early, was severe from the start, e.g. fracture of the larynx, with major ventilatory distress, -or delayed, simple trauma without fracture, becoming manifest only after a few hours with severe dyspnea. In any case, early and late complications of these traumas require, even when they are apparently benign, admission to hospital on a specialised unit able to carry out rapidly respiratory intensive care."}
{"id": "PMID:10820", "title": "[Anesthesia and emergencies in otorhinolaryngology].", "content": "In this paper are considered the etiology, the clinical findings and the management of anaesthesia for a certain number of ENT emergencies, situations of respiratory distress which may lead rapidly to death, or be the cause of severe complications, e.g. -haemorrhage (epistaxis or tonsilar haemorrhage, haemorrhage from carcinoma..), -dyspnea of the adult, neonatal dyspnea and dyspnea of infants and children, -foreign bodies, burns and perforations of the esophagus.", "contents": "[Anesthesia and emergencies in otorhinolaryngology]. In this paper are considered the etiology, the clinical findings and the management of anaesthesia for a certain number of ENT emergencies, situations of respiratory distress which may lead rapidly to death, or be the cause of severe complications, e.g. -haemorrhage (epistaxis or tonsilar haemorrhage, haemorrhage from carcinoma..), -dyspnea of the adult, neonatal dyspnea and dyspnea of infants and children, -foreign bodies, burns and perforations of the esophagus."}
{"id": "PMID:10821", "title": "Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium.", "content": "This was a 60 year old woman, with a very large retro-pharyngeal tumour, mainly situated on the right, revealed by chronic decompensated respiratory failure. Admission to hospital was justified by deep coma with cyanosis of the face and extremities. She had taken 50 mg of Oxazepam the day before admission to hospital. This coma was due to chronic respiratory failure decompensated, as suggested by clinical and laboratory examination after elimination of any traumatic, neurological, endocrine or metabolic disorder. Intubation, rendered difficult by the retro-pharyngeal tumour and assisted ventilation permitted recovery of normal consciousness within 48 hours. This bi-lobed and encapsulated tumor was completely removed after full radiological assessment which showed the absence of any bony lesions. Histology suggested that this was a  benign lipoma. The course was very rapidly favourable with a definite improvement in respiratory function one year after the surgical operation.", "contents": "Lack of a significant protective effect of augmented circulating glucose on the ischemic myocardium. This was a 60 year old woman, with a very large retro-pharyngeal tumour, mainly situated on the right, revealed by chronic decompensated respiratory failure. Admission to hospital was justified by deep coma with cyanosis of the face and extremities. She had taken 50 mg of Oxazepam the day before admission to hospital. This coma was due to chronic respiratory failure decompensated, as suggested by clinical and laboratory examination after elimination of any traumatic, neurological, endocrine or metabolic disorder. Intubation, rendered difficult by the retro-pharyngeal tumour and assisted ventilation permitted recovery of normal consciousness within 48 hours. This bi-lobed and encapsulated tumor was completely removed after full radiological assessment which showed the absence of any bony lesions. Histology suggested that this was a  benign lipoma. The course was very rapidly favourable with a definite improvement in respiratory function one year after the surgical operation."}
{"id": "PMID:10822", "title": "Cardiopulmonary effects of the combination of neuroleptic azaperone and hypnotic metomidate in swine.", "content": "Cardiopulmonary measurements were made at given intervals up to 120 minutes on 6 awake, unanesthetized pigs given azaperone and metomidate. Decreases from control values occurred in arterial blood pressure (deltaBPart = 30 mm of Hg), heart rate (deltaHR = 30 to 35 beats/minute), and cardiac index (deltaCI = 1.5 L/minute/m2). Blood gas and pH measurements indicated no severe impairment of pulmonary function or arterial acidosis. Although the drugs led to decreases in the various functions, cardiopulmonary function remained stable and uncompromised.", "contents": "Cardiopulmonary effects of the combination of neuroleptic azaperone and hypnotic metomidate in swine. Cardiopulmonary measurements were made at given intervals up to 120 minutes on 6 awake, unanesthetized pigs given azaperone and metomidate. Decreases from control values occurred in arterial blood pressure (deltaBPart = 30 mm of Hg), heart rate (deltaHR = 30 to 35 beats/minute), and cardiac index (deltaCI = 1.5 L/minute/m2). Blood gas and pH measurements indicated no severe impairment of pulmonary function or arterial acidosis. Although the drugs led to decreases in the various functions, cardiopulmonary function remained stable and uncompromised."}
{"id": "PMID:10824", "title": "Propoxyphene napsylate.", "content": "Propoxyphene napsylate differs from the hydrochloride salt in several ways. It is much less soluble and bitter and poses few stability problems when capsulated or tableted with aspirin. There is some evidence in several animal species that the pattern and severity of poisoning may be different with the two salts. Equimolar doses of the two salts are probably interchangeable in the relief of pain. The role of propoxyphene in clinical medicine and the questions of propoxyphene abuse and propoxyphene-related fatalities are discussed.", "contents": "Propoxyphene napsylate. Propoxyphene napsylate differs from the hydrochloride salt in several ways. It is much less soluble and bitter and poses few stability problems when capsulated or tableted with aspirin. There is some evidence in several animal species that the pattern and severity of poisoning may be different with the two salts. Equimolar doses of the two salts are probably interchangeable in the relief of pain. The role of propoxyphene in clinical medicine and the questions of propoxyphene abuse and propoxyphene-related fatalities are discussed."}
{"id": "PMID:10825", "title": "Medical problems of surgical patients. Hypertension and ischaemic heart disease.", "content": "Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of 115 patients. The results did not support the view that antihypertensive drugs and beta-receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect beta-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium.", "contents": "Medical problems of surgical patients. Hypertension and ischaemic heart disease. Pre-existing disease in the form of hypertension or ischaemic heart disease may increase morbidity and mortality in patients presenting for anaesthesia and surgery. The interaction of these two cardiovascular conditions in relation to anaesthesia has been studied in a series of 115 patients. The results did not support the view that antihypertensive drugs and beta-receptor blocking agents should be withdrawn before anaesthesia and surgery. The main cause for concern in providing anaesthesia for these patients is that sympathetic nervous activation induced either by anaesthetic manoeuvres or by surgical stimulation may lead to reflex cardiovascular responses which, by increasing myocardial oxygen demand, lead to episodes of myocardial ischaemia. In this respect beta-receptor blocking drugs appear to have a protective effect on the ischaemic myocardium."}
{"id": "PMID:10828", "title": "Effect of organic mercurials and sulfhydryl compounds on the urease activity of Proteus: inhibition by urine and ascorbic acid.", "content": "Meralluride, mercaptomerin, ethacrynic acid, and penicillamine inhibited urease activity of Proteus mirabilis. The activity of the organic mercurials and ethacrynic acid was markedly inhibited by human and dog urine. Antiurease activity could not be detected in the urine of a human and a dog given meralluride by injection. Urine from patients receiving penicillamine also failed to inhibit urease activity. Ascorbic acid inhibited, whereas dehydroascorbic acid enhanced, the activity of the mercurials, but neither agent altered the inhibitory effect of urine. The lethal effect of meralluride against Proteus occurred at the same concentration at which urease activity was inhibited, but penicillamine inhibited the enzymatic activity without affecting viability of the organism. The data suggest that these sulfhydryl-reactive compounds will not be useful against Proteus infections of the urinary tract.", "contents": "Effect of organic mercurials and sulfhydryl compounds on the urease activity of Proteus: inhibition by urine and ascorbic acid. Meralluride, mercaptomerin, ethacrynic acid, and penicillamine inhibited urease activity of Proteus mirabilis. The activity of the organic mercurials and ethacrynic acid was markedly inhibited by human and dog urine. Antiurease activity could not be detected in the urine of a human and a dog given meralluride by injection. Urine from patients receiving penicillamine also failed to inhibit urease activity. Ascorbic acid inhibited, whereas dehydroascorbic acid enhanced, the activity of the mercurials, but neither agent altered the inhibitory effect of urine. The lethal effect of meralluride against Proteus occurred at the same concentration at which urease activity was inhibited, but penicillamine inhibited the enzymatic activity without affecting viability of the organism. The data suggest that these sulfhydryl-reactive compounds will not be useful against Proteus infections of the urinary tract."}
{"id": "PMID:10829", "title": "In vitro study of netilmicin compared with other aminoglycosides.", "content": "Netilmicin (Sch 20569) is an ethyl derivative of gentamicin C(1a) that is active against most Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus isolates. Among 342 clinical isolates tested, all staphylococci; 92% of Escherichia coli, 93% of Klebsiella pneumoniae, and 92% of Enterobacter were inhibited by 0.8 mug or less of netilmicin per ml, but only 78% of P. aeruginosa were inhibited by 3.1 mug or less per ml. Most clinical isolates of enterococci, Serratia marcescens, and Providencia were not inhibited by 3.1 mug of netilmicin per ml. Like other aminoglycosides, the netilmicin in vitro activity was markedly influenced by the growth medium used, with activity decreased by sodium, calcium, and magnesium. Netilmicin was more active at alkaline pH. Addition of magnesium to Pseudomonas or Serratia pretreated with netilmicin produced inhibition of killing. Netilmicin was more active than gentamicin, sisomicin, tobramycin, or amikacin against E. coli and K. pneumoniae. Netilmicin inhibited growth of all gentamicin-resistant isolates of Klebsiella and Citrobacter tested, but only 73% of E. coli; Pseudomonas and Providencia were resistant to netilmicin. Most Serratia (95%) and indole-positive Proteus (83%) isolates were resistant to netilmicin but were inhibited by amikacin.", "contents": "In vitro study of netilmicin compared with other aminoglycosides. Netilmicin (Sch 20569) is an ethyl derivative of gentamicin C(1a) that is active against most Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus isolates. Among 342 clinical isolates tested, all staphylococci; 92% of Escherichia coli, 93% of Klebsiella pneumoniae, and 92% of Enterobacter were inhibited by 0.8 mug or less of netilmicin per ml, but only 78% of P. aeruginosa were inhibited by 3.1 mug or less per ml. Most clinical isolates of enterococci, Serratia marcescens, and Providencia were not inhibited by 3.1 mug of netilmicin per ml. Like other aminoglycosides, the netilmicin in vitro activity was markedly influenced by the growth medium used, with activity decreased by sodium, calcium, and magnesium. Netilmicin was more active at alkaline pH. Addition of magnesium to Pseudomonas or Serratia pretreated with netilmicin produced inhibition of killing. Netilmicin was more active than gentamicin, sisomicin, tobramycin, or amikacin against E. coli and K. pneumoniae. Netilmicin inhibited growth of all gentamicin-resistant isolates of Klebsiella and Citrobacter tested, but only 73% of E. coli; Pseudomonas and Providencia were resistant to netilmicin. Most Serratia (95%) and indole-positive Proteus (83%) isolates were resistant to netilmicin but were inhibited by amikacin."}
{"id": "PMID:10830", "title": "Growth of Physarum gyrosum on agar plates and in liquid culture.", "content": "The physical and nutritional requirements of the antibiotic-producing slime mold Physarum gyrosum were examined to develop a liquid medium for this myxomycete. Liquid culture is desired to expedite a useful scale of production of antibiotic materials for ease of isolation and structure study. Culture conditions were selected to favor antibiotic production rather than maximum growth. The medium devised consisted of 0.010 M potassium phosphate buffer (pH 6.0), 2% bakers' yeast, and 0.2% glucose and was supplemented with either 10(-7) M hemoglobin (preferred) or 2.0 ml of live Escherichia coli per 100 ml of culture medium grown to a steady-state population in nutrient broth. The slime mold, which contained some E. coli carried along with the inoculum, was allowed to grow as a surface plasmodium at 20 degrees C in the dark with weekly subculturing for stocks or for 10 days for antibiotic production. P. gyrosum produced the same antibiotic materials when grown in liquid medium as it did when grown on agar plates. A seeded plate disk assay against Bacillus cereus was employed to follow antibiotic activity.", "contents": "Growth of Physarum gyrosum on agar plates and in liquid culture. The physical and nutritional requirements of the antibiotic-producing slime mold Physarum gyrosum were examined to develop a liquid medium for this myxomycete. Liquid culture is desired to expedite a useful scale of production of antibiotic materials for ease of isolation and structure study. Culture conditions were selected to favor antibiotic production rather than maximum growth. The medium devised consisted of 0.010 M potassium phosphate buffer (pH 6.0), 2% bakers' yeast, and 0.2% glucose and was supplemented with either 10(-7) M hemoglobin (preferred) or 2.0 ml of live Escherichia coli per 100 ml of culture medium grown to a steady-state population in nutrient broth. The slime mold, which contained some E. coli carried along with the inoculum, was allowed to grow as a surface plasmodium at 20 degrees C in the dark with weekly subculturing for stocks or for 10 days for antibiotic production. P. gyrosum produced the same antibiotic materials when grown in liquid medium as it did when grown on agar plates. A seeded plate disk assay against Bacillus cereus was employed to follow antibiotic activity."}
{"id": "PMID:10831", "title": "Suppression of the lytic and bactericidal effects of cell wallinhibitory antibiotics.", "content": "The bacteriolytic effect of beta-lactam antibiotics on Bacillus subtilis and on Streptococcus pneumoniae was found to be a function of the pH; lysis was suppressed if the pH of the pneumococcal culture was below 6.0 during penicillin treatment. In the case of B. subtilis, growth at pH 6.6 prevented penicillin-induced lysis. In pneumococci, the addition of trypsin to the growth medium also protected against lysis. The pH-dependent protection phenomenon resembled in several respects the antibiotic \"tolerance\" of pneumococci with a defective autolytic system. (i) At the pH nonpermissive for lysis, the bacteria retained their normal sensitivity to beta-lactam and to other cell wall inhibitors; however, instead of lysis, the drug-treated bacteria simply stopped growing. Loss of viability of the cells was also greatly reduced. (ii) Protection against lysis was independent of the dose and chemical nature of the cell wall inhibitors. (iii) The protection effect was reversible; lysis and loss of viability could be triggered by a postincubation of the drug-treated bacteria at the pH permissive for lysis.", "contents": "Suppression of the lytic and bactericidal effects of cell wallinhibitory antibiotics. The bacteriolytic effect of beta-lactam antibiotics on Bacillus subtilis and on Streptococcus pneumoniae was found to be a function of the pH; lysis was suppressed if the pH of the pneumococcal culture was below 6.0 during penicillin treatment. In the case of B. subtilis, growth at pH 6.6 prevented penicillin-induced lysis. In pneumococci, the addition of trypsin to the growth medium also protected against lysis. The pH-dependent protection phenomenon resembled in several respects the antibiotic \"tolerance\" of pneumococci with a defective autolytic system. (i) At the pH nonpermissive for lysis, the bacteria retained their normal sensitivity to beta-lactam and to other cell wall inhibitors; however, instead of lysis, the drug-treated bacteria simply stopped growing. Loss of viability of the cells was also greatly reduced. (ii) Protection against lysis was independent of the dose and chemical nature of the cell wall inhibitors. (iii) The protection effect was reversible; lysis and loss of viability could be triggered by a postincubation of the drug-treated bacteria at the pH permissive for lysis."}
{"id": "PMID:10832", "title": "Starch degradation by the mould Trichoderma viride. I. The mechanism of starch degradation.", "content": "The mechanism of starch degradation by the fungus Trichoderma viride was studied in strain CBS 354.44, which utilizes glucose, starch and dextrins but is unable to assimilate maltose. It was shown that the amylolytic enzyme system is completely extracellular, equally well induced by starch, amylose or amylopectin and that it consists mainly of enzymes of the glucoamylase type which yield glucose as the main product of starch hydrolysis. Small amounts of alpha-amylase are produced also. The enzymes produced in starch cultures degrade starch, amylose and amylopectin equally well. Enzyme synthesis in starch media takes place to a considerable extent after exhaustion of the carbon source when maximum growth has been attained. Low-molecular dextrins are degraded by extracellular enzymes of the glucoamylase type. These enzymes are produced in media containing starch or dextrins. Maltotriose is consumed for only one third leaving maltose in the culture filtrate. Maltose is hardly attacked and hardly induces any amylolytic enzyme activity. No stable alpha-glucosidase appears to be produced.", "contents": "Starch degradation by the mould Trichoderma viride. I. The mechanism of starch degradation. The mechanism of starch degradation by the fungus Trichoderma viride was studied in strain CBS 354.44, which utilizes glucose, starch and dextrins but is unable to assimilate maltose. It was shown that the amylolytic enzyme system is completely extracellular, equally well induced by starch, amylose or amylopectin and that it consists mainly of enzymes of the glucoamylase type which yield glucose as the main product of starch hydrolysis. Small amounts of alpha-amylase are produced also. The enzymes produced in starch cultures degrade starch, amylose and amylopectin equally well. Enzyme synthesis in starch media takes place to a considerable extent after exhaustion of the carbon source when maximum growth has been attained. Low-molecular dextrins are degraded by extracellular enzymes of the glucoamylase type. These enzymes are produced in media containing starch or dextrins. Maltotriose is consumed for only one third leaving maltose in the culture filtrate. Maltose is hardly attacked and hardly induces any amylolytic enzyme activity. No stable alpha-glucosidase appears to be produced."}
{"id": "PMID:10833", "title": "Synthesis of chitin by particulate preparations from Aspergillus flavus.", "content": "Cell-free extracts from Aspergillus flavus catalyzed the synthesis of chitin from UDP-GlcNAc. Most of the activity was associated with membrane-rich fractions whereas no activity was detected in the cell walls. Chitin synthetase was activated by fungal acid proteases; animal and plant proteases destroyed it. Upon incubation at 0 C and 28 C chitin synthetase was inactivated, probably by the action of proteases present in the particulate preparations. Maximal activity was obtained at pH 6.6-7.1 and 15 C. Arrhenius plot showed a biphasic curve with the transition at 7 C. E values were 3300 Kcal/mole above this temperature and 15500 Kcal/mole below it. The enzyme was activated by GlcNAc and required a divalent metal, the most active being Mg++. By plotting v vs UDP-GlcNAc concentration a sigmoidal curve was obtained. Km calculated at high substrate concentrations was 20 mM. Chitin synthetase was competitively inhibited by polyoxin D (Ki 6.5 muM) and (Ki 1.35 mM), the latter giving complex kinetics.", "contents": "Synthesis of chitin by particulate preparations from Aspergillus flavus. Cell-free extracts from Aspergillus flavus catalyzed the synthesis of chitin from UDP-GlcNAc. Most of the activity was associated with membrane-rich fractions whereas no activity was detected in the cell walls. Chitin synthetase was activated by fungal acid proteases; animal and plant proteases destroyed it. Upon incubation at 0 C and 28 C chitin synthetase was inactivated, probably by the action of proteases present in the particulate preparations. Maximal activity was obtained at pH 6.6-7.1 and 15 C. Arrhenius plot showed a biphasic curve with the transition at 7 C. E values were 3300 Kcal/mole above this temperature and 15500 Kcal/mole below it. The enzyme was activated by GlcNAc and required a divalent metal, the most active being Mg++. By plotting v vs UDP-GlcNAc concentration a sigmoidal curve was obtained. Km calculated at high substrate concentrations was 20 mM. Chitin synthetase was competitively inhibited by polyoxin D (Ki 6.5 muM) and (Ki 1.35 mM), the latter giving complex kinetics."}
{"id": "PMID:10834", "title": "The regulation of agarase production by resting cells of Cytophaga flevenis.", "content": "The regulation of the synthesis of extracellular agarase by Cytophaga flevensis was studied in resting-cell suspensions. Enzyme synthesis was strictly dependent on the presence of a suitable inducer. Enzyme production was maximal at 20 C in phosphate buffer pH 6.9 in the presence of 1.3 mM calcium chloride, 0.03% casamino acids and inducer. Enzyme production was virtually the same at 15 and 20 C, reduced to 50% at 25 C and was not detectable at 30 C. It was highly stimulated by the presence of 0.03% of casamino acids in the incubation mixture and was also favoured by the presence of 1.3 mM calcium ions. Of a variety of compounds tested, only melibiose or neoagaro-oligosaccharides were effective inducers. Among the neoagaro-oligosaccharides, neoagarotetraose was the best inducer. At higher concentrations of inducer compounds catabolite repression of enzyme synthesis was apparent. This was also found when glucose was added to the incubation mixture. This repression was not relieved by the addition of cyclic AMP. Indications were found that the excretion process was limiting the rate of production of extracellular enzyme", "contents": "The regulation of agarase production by resting cells of Cytophaga flevenis. The regulation of the synthesis of extracellular agarase by Cytophaga flevensis was studied in resting-cell suspensions. Enzyme synthesis was strictly dependent on the presence of a suitable inducer. Enzyme production was maximal at 20 C in phosphate buffer pH 6.9 in the presence of 1.3 mM calcium chloride, 0.03% casamino acids and inducer. Enzyme production was virtually the same at 15 and 20 C, reduced to 50% at 25 C and was not detectable at 30 C. It was highly stimulated by the presence of 0.03% of casamino acids in the incubation mixture and was also favoured by the presence of 1.3 mM calcium ions. Of a variety of compounds tested, only melibiose or neoagaro-oligosaccharides were effective inducers. Among the neoagaro-oligosaccharides, neoagarotetraose was the best inducer. At higher concentrations of inducer compounds catabolite repression of enzyme synthesis was apparent. This was also found when glucose was added to the incubation mixture. This repression was not relieved by the addition of cyclic AMP. Indications were found that the excretion process was limiting the rate of production of extracellular enzyme"}
{"id": "PMID:10835", "title": "Influences of soil acidity on Streptomyces populations inhabiting forest soils.", "content": "The Streptomyces populations inhabiting five acidic forest soils were examined. It was found that lowering the pH of a medium selective for streptomycetes (starch-casein agar) to the pH of the particular soil horizon being plated influenced both the total numbers and types of streptomycetes that were isolated from the soils examined in this study. On the acidified medium both the numbers of streptomycetes and the percentage of total bacteria on the plates represented by streptomycetes increased (as compared with the same medium with a pH of 7.2). These differences were greatest on the isolations from the most acid soils. The largest concentrations of streptomycetes were found in the surface horizon (0 to 15 cm) and the litter layer immediately over the surface mineral horizon. Acidity tolerance tests demonstrated that random samplings of isolates contained acidophilic, neutrophilic, and acidoduric strains, with the largest numbers of acidophiles being found on the acidified media from the most acid soils. There were no differences between overall utilization of selected carbohydrates among the isolates taken from either the neutral or acidic media, although a larger proportion of the acid media isolates produced acid from the carbohydrates. Evidence is presented which indicates that different types of streptomycetes were isolated on the acid media, and possible reasons for the presence of these acid-tolerant populations are discussed.", "contents": "Influences of soil acidity on Streptomyces populations inhabiting forest soils. The Streptomyces populations inhabiting five acidic forest soils were examined. It was found that lowering the pH of a medium selective for streptomycetes (starch-casein agar) to the pH of the particular soil horizon being plated influenced both the total numbers and types of streptomycetes that were isolated from the soils examined in this study. On the acidified medium both the numbers of streptomycetes and the percentage of total bacteria on the plates represented by streptomycetes increased (as compared with the same medium with a pH of 7.2). These differences were greatest on the isolations from the most acid soils. The largest concentrations of streptomycetes were found in the surface horizon (0 to 15 cm) and the litter layer immediately over the surface mineral horizon. Acidity tolerance tests demonstrated that random samplings of isolates contained acidophilic, neutrophilic, and acidoduric strains, with the largest numbers of acidophiles being found on the acidified media from the most acid soils. There were no differences between overall utilization of selected carbohydrates among the isolates taken from either the neutral or acidic media, although a larger proportion of the acid media isolates produced acid from the carbohydrates. Evidence is presented which indicates that different types of streptomycetes were isolated on the acid media, and possible reasons for the presence of these acid-tolerant populations are discussed."}
{"id": "PMID:10836", "title": "Factors affecting production of mold mycelium and protein in synthetic media.", "content": "The effects of certain cultural conditions on the yield of dry mycelium, protein, and total amino acid content of Rhizopus oligosporus Saito (NRRL 2710), Rhizopus rhizopodiformis (Cohn apud Lichtheim) Zopf (NRRL 6246), and Absidia corymbifera (Cohn) Sacc. et Trotter (NRRL 6247) were studied. The yield of mycelium was found to significantly increase as the spore inoculum was increased from 187,500 to 2,250,000 spores. But the total amino acids (grams/liter) did not change significantly, whereas the percentage of crude protein decreased. An inoculum containing approximately 750,000 spores/ml was used in all of the other experiments. Mycelial production was highest at 37 degrees C for all three molds. However, the best temperature for percentage of crude protein and total amino acids varied with the organism. The mycelial yield and total crude protein of R. oligosporus showed some significant changes as the C/N ratio was increased in 3% glucose medium. In a synthetic medium having a 15:1 C/N ratio, the strains of R. oligosporus, R. rhizopodiformis, and A. corymbifera had better yields from falactose than glucose, not only in dry mycelium but also in total crude protein (grams/liter) and total amino acids (grams/liter). R. oligosporus grew very well on several ammonium salts. but the maximum yield of dry mycelium, total crude protein (grams/liter), and total amino acids (grams/liter) occurred with ammonium sulfate. The optimum pH for both Rhizopus species was 4.0, although R. oligosporus grew equally well at pH 3.0 and slightly less at pH 5.0. The highest yield of mycelium for A. corymbifera was obtained in a medium with an initial pH of 8.0. It was calculated that a fermenter chanrged with an adequate medium and 1,000 lb (about 450 kg) of R. oligosporus or A. corymbifera cells could produce 88 or 90 lb of protein (on a dry-weight basis) per h if the product was removed continuously.", "contents": "Factors affecting production of mold mycelium and protein in synthetic media. The effects of certain cultural conditions on the yield of dry mycelium, protein, and total amino acid content of Rhizopus oligosporus Saito (NRRL 2710), Rhizopus rhizopodiformis (Cohn apud Lichtheim) Zopf (NRRL 6246), and Absidia corymbifera (Cohn) Sacc. et Trotter (NRRL 6247) were studied. The yield of mycelium was found to significantly increase as the spore inoculum was increased from 187,500 to 2,250,000 spores. But the total amino acids (grams/liter) did not change significantly, whereas the percentage of crude protein decreased. An inoculum containing approximately 750,000 spores/ml was used in all of the other experiments. Mycelial production was highest at 37 degrees C for all three molds. However, the best temperature for percentage of crude protein and total amino acids varied with the organism. The mycelial yield and total crude protein of R. oligosporus showed some significant changes as the C/N ratio was increased in 3% glucose medium. In a synthetic medium having a 15:1 C/N ratio, the strains of R. oligosporus, R. rhizopodiformis, and A. corymbifera had better yields from falactose than glucose, not only in dry mycelium but also in total crude protein (grams/liter) and total amino acids (grams/liter). R. oligosporus grew very well on several ammonium salts. but the maximum yield of dry mycelium, total crude protein (grams/liter), and total amino acids (grams/liter) occurred with ammonium sulfate. The optimum pH for both Rhizopus species was 4.0, although R. oligosporus grew equally well at pH 3.0 and slightly less at pH 5.0. The highest yield of mycelium for A. corymbifera was obtained in a medium with an initial pH of 8.0. It was calculated that a fermenter chanrged with an adequate medium and 1,000 lb (about 450 kg) of R. oligosporus or A. corymbifera cells could produce 88 or 90 lb of protein (on a dry-weight basis) per h if the product was removed continuously."}
{"id": "PMID:10837", "title": "Oxidation of arsenite to arsenate by Alcaligenes faecalis.", "content": "Alcaligenes faecalis, resistant to the toxic effects of 0.01 M sodium arsenite, was isolated from raw sewage and shown to be capable of oxidizing arsenite to arsenate. When the organisms were grown in chemically defined medium, this conversion was due to the appearance at stationary phase of an intracellular, oxygen-sensitive, inducible enzyme and/or component of the electron transport system; when the organisms were grown in a nutrient broth-yeast extract medium, the enzyme appeared in the late exponential phase of growth. The presence of 0.02 M arsenite in the culture medium affected neither growth rate nor final cell yield.", "contents": "Oxidation of arsenite to arsenate by Alcaligenes faecalis. Alcaligenes faecalis, resistant to the toxic effects of 0.01 M sodium arsenite, was isolated from raw sewage and shown to be capable of oxidizing arsenite to arsenate. When the organisms were grown in chemically defined medium, this conversion was due to the appearance at stationary phase of an intracellular, oxygen-sensitive, inducible enzyme and/or component of the electron transport system; when the organisms were grown in a nutrient broth-yeast extract medium, the enzyme appeared in the late exponential phase of growth. The presence of 0.02 M arsenite in the culture medium affected neither growth rate nor final cell yield."}
{"id": "PMID:10838", "title": "Defined conditions for synthesis of Bacillus cereus enterotoxin by fermenter-grown cultures.", "content": "A strain of Bacillus cereus produced high levels of enterotoxin when grown in a semidefined medium in a laboratory scale fermenter. The optimum conditions for enterotoxin synthesis by cultures grown in this medium, which contained Casamino Acids and yeast extract, were found to be: inoculation of vigorously gorwing culture at the 1% level, addition of glucose at a concentration of 1%, control of culture pH at 8.0, incubation at 32 degrees C, use of a moderate stirring rate, and addition of air at low flow rates to minimize foaming. The enterotoxin yield in fermenter-grown cultures was approximately 20 to 50 times higher than the yield obtained in shake flask cultures.", "contents": "Defined conditions for synthesis of Bacillus cereus enterotoxin by fermenter-grown cultures. A strain of Bacillus cereus produced high levels of enterotoxin when grown in a semidefined medium in a laboratory scale fermenter. The optimum conditions for enterotoxin synthesis by cultures grown in this medium, which contained Casamino Acids and yeast extract, were found to be: inoculation of vigorously gorwing culture at the 1% level, addition of glucose at a concentration of 1%, control of culture pH at 8.0, incubation at 32 degrees C, use of a moderate stirring rate, and addition of air at low flow rates to minimize foaming. The enterotoxin yield in fermenter-grown cultures was approximately 20 to 50 times higher than the yield obtained in shake flask cultures."}
{"id": "PMID:10839", "title": "Survival of coliform bacteria in sewage sludge applied to a forest clearcut and potential movement into groundwater.", "content": "Anaerobically digested dewatered sludge (10 to 15 cm thick) was applied to a forest clearcut as a fertilizer source in northwest Washington on gravelly glacial outwash soil. This sludge is not microbiologically sterile and may contain pathogenic organisms. Fecal coliform bacterial counts in sludge applied in summer (July) fell from 1.08 X 10(5) to 358/g in 204 days and to 0/g in 267 days. Dieoff appeared more rapid in winter (January)-applied sludge, when colnts fell from 1.2 X 10(5) to 20/g in 162 days. Initial death rates were related to sludge temperature, moisture, pH, physical composition, and microbial competition. Aftergrowth of fecal coliforms occurred in warm summer and fall months, but counts were of similar magnitude to background levels in forest soils, where a maximum count of 54/g was recorded. Total coliform counts in fresh sludge ranged from 1.4 X 10(4) to 1.9 X 10(6)/g. Numbers stabilized at 10(3) to 10(4)/g in spring, fall, and summer, with lower numbers in winter. Both total and fecal bacteria moved from the sludge to the soil beneath, but few penetrated past the first 5 cm. The soil acts as an effective biological filter. Few fecal coliform bacteria were recorded in the groundwater, generally being less than 5/100 ml and mostly 0/100 ml. A maximum count of 52/100 ml was recorded. Groundwater contamination from vertical movement of potential pathogens appears unlikely, but hazards from surface runoff and direct handling in the first year may arise.", "contents": "Survival of coliform bacteria in sewage sludge applied to a forest clearcut and potential movement into groundwater. Anaerobically digested dewatered sludge (10 to 15 cm thick) was applied to a forest clearcut as a fertilizer source in northwest Washington on gravelly glacial outwash soil. This sludge is not microbiologically sterile and may contain pathogenic organisms. Fecal coliform bacterial counts in sludge applied in summer (July) fell from 1.08 X 10(5) to 358/g in 204 days and to 0/g in 267 days. Dieoff appeared more rapid in winter (January)-applied sludge, when colnts fell from 1.2 X 10(5) to 20/g in 162 days. Initial death rates were related to sludge temperature, moisture, pH, physical composition, and microbial competition. Aftergrowth of fecal coliforms occurred in warm summer and fall months, but counts were of similar magnitude to background levels in forest soils, where a maximum count of 54/g was recorded. Total coliform counts in fresh sludge ranged from 1.4 X 10(4) to 1.9 X 10(6)/g. Numbers stabilized at 10(3) to 10(4)/g in spring, fall, and summer, with lower numbers in winter. Both total and fecal bacteria moved from the sludge to the soil beneath, but few penetrated past the first 5 cm. The soil acts as an effective biological filter. Few fecal coliform bacteria were recorded in the groundwater, generally being less than 5/100 ml and mostly 0/100 ml. A maximum count of 52/100 ml was recorded. Groundwater contamination from vertical movement of potential pathogens appears unlikely, but hazards from surface runoff and direct handling in the first year may arise."}
{"id": "PMID:10840", "title": "Dense autotrophic cultures of Alcaligenes eutrophus.", "content": "Alcaligenes eutrophus was grown autotrophically in 23-liter batch cultures in a controlled H2-O2-CO2 atmosphere. It was demonstrated that the need for periodic supplements of individual nutrients could be anticipated before cell growth depleted these nutrients to the point of becoming growth rate limiting. As a result, exponential growth was extended to optical densities of 44, with doubling times maintained at 2 h. Cultures having an initial optical density of 0.040 to 0.70 reached the final optical density of 60 in about 25 h. The final viable count was 1.2 X 10(11) cells per ml, and the dry weight was 25 g/liter.", "contents": "Dense autotrophic cultures of Alcaligenes eutrophus. Alcaligenes eutrophus was grown autotrophically in 23-liter batch cultures in a controlled H2-O2-CO2 atmosphere. It was demonstrated that the need for periodic supplements of individual nutrients could be anticipated before cell growth depleted these nutrients to the point of becoming growth rate limiting. As a result, exponential growth was extended to optical densities of 44, with doubling times maintained at 2 h. Cultures having an initial optical density of 0.040 to 0.70 reached the final optical density of 60 in about 25 h. The final viable count was 1.2 X 10(11) cells per ml, and the dry weight was 25 g/liter."}
{"id": "PMID:10841", "title": "Organic flocculation: an efficient second-step concentration method for the detection of viruses in tap water.", "content": "A method is described for second-step concentration of viruses from water. This method, combined with an adsorption-elution method, yields a mean recovery of about 75%", "contents": "Organic flocculation: an efficient second-step concentration method for the detection of viruses in tap water. A method is described for second-step concentration of viruses from water. This method, combined with an adsorption-elution method, yields a mean recovery of about 75%"}
{"id": "PMID:10842", "title": "Reconcentration of poliovirus from sewage.", "content": "Virus can be adsorbed from effluents of sewage treatment plants on large-surface membranes. Subsequent elution of virus requires large volumes, which in turn requires reconcentration of virus for assay. However, reconcentration of such viral eluates on small adsorbent surfaces is difficult because certain soluble sewage components are adsorbed along with the virus on the initial virus adsorbent and are removed along with the virus by the eluent. Upon acidification of the initial eluate to reconcentrate the virus on smaller membrane surfaces, flocs are formed that interfere with the reconcentration process. To circumvent this problem, the interfering sewage components can be removed by activated carbon and ion-exchange resins. The virus is then readily reconcentrated on small membranes.", "contents": "Reconcentration of poliovirus from sewage. Virus can be adsorbed from effluents of sewage treatment plants on large-surface membranes. Subsequent elution of virus requires large volumes, which in turn requires reconcentration of virus for assay. However, reconcentration of such viral eluates on small adsorbent surfaces is difficult because certain soluble sewage components are adsorbed along with the virus on the initial virus adsorbent and are removed along with the virus by the eluent. Upon acidification of the initial eluate to reconcentrate the virus on smaller membrane surfaces, flocs are formed that interfere with the reconcentration process. To circumvent this problem, the interfering sewage components can be removed by activated carbon and ion-exchange resins. The virus is then readily reconcentrated on small membranes."}
{"id": "PMID:10843", "title": "Concentration and purification of enteroviruses by membrane chromatography.", "content": "A simple procedure for the concentration and partial purification of enteroviruses from tissue culture harvests is described. After removal of acid-precipitating components with a cationic detergent, the detergent and most membrane-coating components were removed by treatment with a cationic-exchange resin. The resin effluent was then acidified, and the virus was adsorbed to epoxy-fiberglass membranes. Virus was then eluted with pH 11.5 glycine-NaOH buffer. Since this eluate contains no orgcentrated simply by acidifying the eluate and passing it through a smaller membrane than that used for the first concentration. As high as 500-fold concentrations can be achieved, with a high efficiency of recovery.", "contents": "Concentration and purification of enteroviruses by membrane chromatography. A simple procedure for the concentration and partial purification of enteroviruses from tissue culture harvests is described. After removal of acid-precipitating components with a cationic detergent, the detergent and most membrane-coating components were removed by treatment with a cationic-exchange resin. The resin effluent was then acidified, and the virus was adsorbed to epoxy-fiberglass membranes. Virus was then eluted with pH 11.5 glycine-NaOH buffer. Since this eluate contains no orgcentrated simply by acidifying the eluate and passing it through a smaller membrane than that used for the first concentration. As high as 500-fold concentrations can be achieved, with a high efficiency of recovery."}
{"id": "PMID:10844", "title": "Growth and toxin production by Clostridium botulinum in moldy tomato juice.", "content": "Tomato juice inoculated with Cladosporium sp. or Penicillium sp. developed pH gradients with the upper portions near the mold mats having pH values near neutrality and the lower portions remaining more acid. Clostridium botulinum spores in these moldy tomato juices germinated, grew out, and produced toxin.", "contents": "Growth and toxin production by Clostridium botulinum in moldy tomato juice. Tomato juice inoculated with Cladosporium sp. or Penicillium sp. developed pH gradients with the upper portions near the mold mats having pH values near neutrality and the lower portions remaining more acid. Clostridium botulinum spores in these moldy tomato juices germinated, grew out, and produced toxin."}
{"id": "PMID:10857", "title": "Release of immunoreactive serotonin following acid perfusion of the duodenum.", "content": "Cannulas were placed in the portal vein, hepatic vein, and infrarenal vena cava in eight anesthetized dogs. The duodenum of each dog was irrigated with saline (control) and 0.1 N HCI (50 ml in 10 min). Heparinized blood samples were taken from each cannula 5 min before, and 1, 5, 10, 30 and 60 min after each irrigation for measurement of immunoreactive serotonin concentrations. Serotonin concentrations did not change during saline irrigation of the duodenum. In contrast, serotonin release was consistently observed after duodenal acidification (pH 1.5-2.0). Portal venous serotonin concentrations were increased at 1 min (356 +/- 147 ng/ml) and following a biphasic pattern remained elevated at 30 and 60 min (499 +/- 131 and 489 +/- 187 ng/ml, respectively). Concentrations in the hepatic vein rose more slowly and to a lower peak (357 +/- 123 ng/ml at 10 min). Caval serotonin concentrations were increased at 10 min (342 +/- 121 ng/ml) but promptly returned to baseline levels. In the canine gastrointestinal tract, immunoreactive serotonin concentrations were highest in the duodenal bulb (15.4 mug/gm). This study demonstrated serotonin release from the duodenum following acid perfusion and documented that some of the released serotonin escaped hepatic inactivation. These findings support the possibility that serotonin may be a gastrointestinal hormone involved in the feedback inhibition of gastric acid secretion.", "contents": "Release of immunoreactive serotonin following acid perfusion of the duodenum. Cannulas were placed in the portal vein, hepatic vein, and infrarenal vena cava in eight anesthetized dogs. The duodenum of each dog was irrigated with saline (control) and 0.1 N HCI (50 ml in 10 min). Heparinized blood samples were taken from each cannula 5 min before, and 1, 5, 10, 30 and 60 min after each irrigation for measurement of immunoreactive serotonin concentrations. Serotonin concentrations did not change during saline irrigation of the duodenum. In contrast, serotonin release was consistently observed after duodenal acidification (pH 1.5-2.0). Portal venous serotonin concentrations were increased at 1 min (356 +/- 147 ng/ml) and following a biphasic pattern remained elevated at 30 and 60 min (499 +/- 131 and 489 +/- 187 ng/ml, respectively). Concentrations in the hepatic vein rose more slowly and to a lower peak (357 +/- 123 ng/ml at 10 min). Caval serotonin concentrations were increased at 10 min (342 +/- 121 ng/ml) but promptly returned to baseline levels. In the canine gastrointestinal tract, immunoreactive serotonin concentrations were highest in the duodenal bulb (15.4 mug/gm). This study demonstrated serotonin release from the duodenum following acid perfusion and documented that some of the released serotonin escaped hepatic inactivation. These findings support the possibility that serotonin may be a gastrointestinal hormone involved in the feedback inhibition of gastric acid secretion."}
{"id": "PMID:10858", "title": "Use of profound hypothermia induced by surface cooling in open-heart surgery.", "content": "Profound hypothermia with body-surface cooling for use in open-heart surgery is considered a difficult anesthetic technique because of the problems of controlling ether anesthesia. This paper describes our hypothermia technique in detail, with emphasis on its particular usefulness in open-heart procedures in neonates and infants. The results are based on our experience with 281 consecutive patients. Guidelines for safe and effective performance of this technique were established on the basis of continuous monitoring of the electrocardiogram, electroencephalogram, and arterial blood pressure. We conclude from our experience that open-heart operation under profound hypothermia is a safe, effective, and extremely promising method.", "contents": "Use of profound hypothermia induced by surface cooling in open-heart surgery. Profound hypothermia with body-surface cooling for use in open-heart surgery is considered a difficult anesthetic technique because of the problems of controlling ether anesthesia. This paper describes our hypothermia technique in detail, with emphasis on its particular usefulness in open-heart procedures in neonates and infants. The results are based on our experience with 281 consecutive patients. Guidelines for safe and effective performance of this technique were established on the basis of continuous monitoring of the electrocardiogram, electroencephalogram, and arterial blood pressure. We conclude from our experience that open-heart operation under profound hypothermia is a safe, effective, and extremely promising method."}
{"id": "PMID:10859", "title": "Inhibition of adjuvant arthritis by histamine.", "content": "Histamine was injected subcutaneously to rats at doses of 2--10 mg/kg, twice daily for various periods after an intradermal adjuvant injection into one hind paw. The administration of histamine prevented the appearance of the secondary lesion in the noninjected paw, but did not affect the primary swelling of the injected paw or the established secondary lesion. The histamine effect was dose-dependent with the most effective time of administration being from the 5th to the 10th day after adjuvant injection. Arthritic lesions found in control animals in histological and roentgenographic examinations were also inhibited in histamine-treated animals. Sinomenine, a histamine releaser, likewise showed a suppressive effect on the secondary lesion. Burimamide, a histamine H2-receptor antagonist, blocked these histamine effects, while mepyramine, a H1-receptor antagonist, did not have such a blocking effect. The findings suggest that histamine may inhibit the development of adjuvant arthritis by an immunosuppressive mechanism mediated through activation of H2-receptors on lymphoid cells.", "contents": "Inhibition of adjuvant arthritis by histamine. Histamine was injected subcutaneously to rats at doses of 2--10 mg/kg, twice daily for various periods after an intradermal adjuvant injection into one hind paw. The administration of histamine prevented the appearance of the secondary lesion in the noninjected paw, but did not affect the primary swelling of the injected paw or the established secondary lesion. The histamine effect was dose-dependent with the most effective time of administration being from the 5th to the 10th day after adjuvant injection. Arthritic lesions found in control animals in histological and roentgenographic examinations were also inhibited in histamine-treated animals. Sinomenine, a histamine releaser, likewise showed a suppressive effect on the secondary lesion. Burimamide, a histamine H2-receptor antagonist, blocked these histamine effects, while mepyramine, a H1-receptor antagonist, did not have such a blocking effect. The findings suggest that histamine may inhibit the development of adjuvant arthritis by an immunosuppressive mechanism mediated through activation of H2-receptors on lymphoid cells."}
{"id": "PMID:10860", "title": "Effects of propranolo, itramin tosylate and dipyridamole on myocardial phosphate metabolism in anoxic perfused rat hearts.", "content": "Effects of propranolo, itramin tosylate and dipyridamole on coronary flow, cardiac activity and phosphate metabolism were investigated in anoxic perfused rat hearts. During anoxia, heart contractions showed a transient increase followed by gradual declines in amplitude and frequency, while ATP and creatine phosphate (CP) contents strikingly decreased accompanying a pronounced increase in inorganic phosphate (Pi). Propranolol added to the anoxic perfusate attenuated the decrease in CP and increase in Pi, whereas heart contractions wre more markedly depressed than by anoxia alone. Similar effects were also seen in electrically paced anoxic hearts. Itramin decreased ATP contents in non-paced anoxic hearts, but did not in paced ones. Dipyridamole did not produce any significant effect on phosphate metabolism in anoxic myocardium. It was considered that propranolol prevented the anoxia-induced reduction in high-energy phosphates by antagonizing catecholamines released by anoxia and that itramin decreased ATP level by inhibiting ATP generation.", "contents": "Effects of propranolo, itramin tosylate and dipyridamole on myocardial phosphate metabolism in anoxic perfused rat hearts. Effects of propranolo, itramin tosylate and dipyridamole on coronary flow, cardiac activity and phosphate metabolism were investigated in anoxic perfused rat hearts. During anoxia, heart contractions showed a transient increase followed by gradual declines in amplitude and frequency, while ATP and creatine phosphate (CP) contents strikingly decreased accompanying a pronounced increase in inorganic phosphate (Pi). Propranolol added to the anoxic perfusate attenuated the decrease in CP and increase in Pi, whereas heart contractions wre more markedly depressed than by anoxia alone. Similar effects were also seen in electrically paced anoxic hearts. Itramin decreased ATP contents in non-paced anoxic hearts, but did not in paced ones. Dipyridamole did not produce any significant effect on phosphate metabolism in anoxic myocardium. It was considered that propranolol prevented the anoxia-induced reduction in high-energy phosphates by antagonizing catecholamines released by anoxia and that itramin decreased ATP level by inhibiting ATP generation."}
{"id": "PMID:10861", "title": "Possible mechanisms involved in the coronary vasodilatory response to dopamine.", "content": "Dopamine increased coronary blood flow in the dog heart pretreated with alpha-adrenoceptor blocking agents. The coronary vasodilator response was completely inhibited by indomethacin when pretreated with propranolol in addition to alpha blockade. The coronary vasodilation exerted by sodium nitrite was potentiated by indomethacin and adrenergic blockade. In coronary arterial strips, dopamine produced a contraction which was abolished by phenoxybenzamine. Dopamine elicited a dose-dependent relaxation in coronary arterial strips contracted previously by KC1 after pretreatment with phenoxybenzamine. The relaxation was potentiated by indomethacin; this effect was completely blocked by propranolol. Prostaglandin (PG)E1 produced a relaxing response but reduced the dopamine-induced relaxation. From the results it is suggested that beta-adrenoceptor stimulation and release of PG were involved in the coronary vasodilator response to dopamine. PG released by dopamine may increase coronary blood flow on the one hand and reduce beta-adrenoceptor stimulation by inhibiting adenyl cyclase on the other.", "contents": "Possible mechanisms involved in the coronary vasodilatory response to dopamine. Dopamine increased coronary blood flow in the dog heart pretreated with alpha-adrenoceptor blocking agents. The coronary vasodilator response was completely inhibited by indomethacin when pretreated with propranolol in addition to alpha blockade. The coronary vasodilation exerted by sodium nitrite was potentiated by indomethacin and adrenergic blockade. In coronary arterial strips, dopamine produced a contraction which was abolished by phenoxybenzamine. Dopamine elicited a dose-dependent relaxation in coronary arterial strips contracted previously by KC1 after pretreatment with phenoxybenzamine. The relaxation was potentiated by indomethacin; this effect was completely blocked by propranolol. Prostaglandin (PG)E1 produced a relaxing response but reduced the dopamine-induced relaxation. From the results it is suggested that beta-adrenoceptor stimulation and release of PG were involved in the coronary vasodilator response to dopamine. PG released by dopamine may increase coronary blood flow on the one hand and reduce beta-adrenoceptor stimulation by inhibiting adenyl cyclase on the other."}
{"id": "PMID:10862", "title": "Studies concerning dopamine diuresis in the rat.", "content": "Dopamine is both diuretic and saluretic in the conscious rat. The diuretic effect does not appear to be beta-receptor mediated, but rather may be the result of a combination of alpha- and dopaminergic receptor stimulation. Conclusive proof for the existence of the latter, however, must await the discovery of a more selective peripheral dopamine-receptor stimulant than is dopamine per se.", "contents": "Studies concerning dopamine diuresis in the rat. Dopamine is both diuretic and saluretic in the conscious rat. The diuretic effect does not appear to be beta-receptor mediated, but rather may be the result of a combination of alpha- and dopaminergic receptor stimulation. Conclusive proof for the existence of the latter, however, must await the discovery of a more selective peripheral dopamine-receptor stimulant than is dopamine per se."}
{"id": "PMID:10863", "title": "Selective blocking properties of chloro acetyl catechol (CAC) on the alpha-adrenergic receptor.", "content": "In anesthetized rats and cats chloro acetyl catechol (CAC, 10 mg/kg i.v. and 10-15 mg/kg i.v., respectively) selectively blocked the arterial hypertensive responses to epinephrine. No adrenergic blockade was produced by CAC in rats pretreated with 20 mg/kg i.p. of the compound 24 hr before the experiment. Norepinephrine-induced contractions of the rat vas deferens and the rat seminal vesicles in vitro were blocked by CAC 10(-4) M. The blockade was prevented by the simultaneous addition of norepinephrine or cysteine. The data are discussed in relation to : (a) the nature of the adrenergic blockade produced by CAC and (b) the possible existence of thiol groups in the vicinity of the active site of the alpha-adrenergic receptor.", "contents": "Selective blocking properties of chloro acetyl catechol (CAC) on the alpha-adrenergic receptor. In anesthetized rats and cats chloro acetyl catechol (CAC, 10 mg/kg i.v. and 10-15 mg/kg i.v., respectively) selectively blocked the arterial hypertensive responses to epinephrine. No adrenergic blockade was produced by CAC in rats pretreated with 20 mg/kg i.p. of the compound 24 hr before the experiment. Norepinephrine-induced contractions of the rat vas deferens and the rat seminal vesicles in vitro were blocked by CAC 10(-4) M. The blockade was prevented by the simultaneous addition of norepinephrine or cysteine. The data are discussed in relation to : (a) the nature of the adrenergic blockade produced by CAC and (b) the possible existence of thiol groups in the vicinity of the active site of the alpha-adrenergic receptor."}
{"id": "PMID:10864", "title": "The cardiovascular pharmacology and hemodynamic activity of tazolol, a selective myocardial beta-stimulant.", "content": "The pharmacology and hemodynamics of tazolol (1-iso-propylamino-3-(2-thiazoloxy)-2-propranolol HC1), a selective myocardial beta-stimulant, were studied in pentobarbital anesthetized dogs. Tazolol, i.v., increased myocardial contractile force and heart rate, but induced only minimal changes in arterial pressure. The cardiac effects of tazolol were blocked by pretreatment with the beta-blockers propranolol or practolol and inhibited in animals made tachyphylactic to amphetamine. They were not altered by pretreatment with hexamehtonium, atropine or reserpine. Tazolol increased left circumflex coronary artery flow to a far greater extent than a dose level of isoproterenol which produced a greater increase in cardiac output. Tazolol also increased superior mesenteric artery flow, whereas isoproterenol decreased it. Renal artery flow was not altered. Tazolol was also found to be orally active and to possess some mild general beta-blocking activity.", "contents": "The cardiovascular pharmacology and hemodynamic activity of tazolol, a selective myocardial beta-stimulant. The pharmacology and hemodynamics of tazolol (1-iso-propylamino-3-(2-thiazoloxy)-2-propranolol HC1), a selective myocardial beta-stimulant, were studied in pentobarbital anesthetized dogs. Tazolol, i.v., increased myocardial contractile force and heart rate, but induced only minimal changes in arterial pressure. The cardiac effects of tazolol were blocked by pretreatment with the beta-blockers propranolol or practolol and inhibited in animals made tachyphylactic to amphetamine. They were not altered by pretreatment with hexamehtonium, atropine or reserpine. Tazolol increased left circumflex coronary artery flow to a far greater extent than a dose level of isoproterenol which produced a greater increase in cardiac output. Tazolol also increased superior mesenteric artery flow, whereas isoproterenol decreased it. Renal artery flow was not altered. Tazolol was also found to be orally active and to possess some mild general beta-blocking activity."}
{"id": "PMID:10865", "title": "Influence of adrenaline, dibenamine and dopamine on acidosis, hemoconcentration and lethality in protracted anaphylactic shock of guinea-pigs.", "content": "Protracted anaphylactic shock of guinea-pigs was accompanied by a marked decrease in blood pH, and an increase in hematocrit. Death ensued in 58.3% of the animals within 3 hr of observation. Infusion of adrenaline (20 mug/kg/min), after eliciting anaphylaxis, intensified the acidosis, and increased the lethality to 100%. Pretreatment with dibenamine (5 mg/kg) reversed the effect of adrenaline. Dopamine, infused in amounts of 200 mug/kg/min, acted similarly to the combination dibenamine/adrenaline. Hemoconcentration was neither prevented nor intensified by adrenaline. Dopamine, however, reduced significantly the anaphylactic increase in hematocrit.", "contents": "Influence of adrenaline, dibenamine and dopamine on acidosis, hemoconcentration and lethality in protracted anaphylactic shock of guinea-pigs. Protracted anaphylactic shock of guinea-pigs was accompanied by a marked decrease in blood pH, and an increase in hematocrit. Death ensued in 58.3% of the animals within 3 hr of observation. Infusion of adrenaline (20 mug/kg/min), after eliciting anaphylaxis, intensified the acidosis, and increased the lethality to 100%. Pretreatment with dibenamine (5 mg/kg) reversed the effect of adrenaline. Dopamine, infused in amounts of 200 mug/kg/min, acted similarly to the combination dibenamine/adrenaline. Hemoconcentration was neither prevented nor intensified by adrenaline. Dopamine, however, reduced significantly the anaphylactic increase in hematocrit."}
{"id": "PMID:10866", "title": "Effects of lithium and rubidium on antinociception and behaviour in mice. I. Studies on narcotic analgesics and antagonists.", "content": "The effects of acute and chronic LiCl and RbCl treatments on the antinociception caused by morphine, pethidine, methadone, pentazocine, nalorphine or naloxone were studied in mice using the hot plate and phenylquinone writhing tests. In both tests morphine, pethidine, and methadone caused significant antinociception whereas the antagonistic drugs were almost inactive. In the hot plate test both the 21 day administration of LiCl and the 5 and 21 day administration of RbCl decreased the antinociceptive effect of morphine. The 5 day administration of LiCl increased the antinociceptive effect of pethidine whereas the acute and 5 day administrations of RbCl abolished it. There were no significant or consistent interactions of the ions with the antinociceptive effect of methadone or the antagonistic drugs. In the phenylquinone writhing test the effects of the ions were inconsistent. Especially in the acute experiments where LiCl and RbCl had some effects on the behaviour of the mice treated with the analgesics, LiCl mostly impaired motor coordination and motor activity whereas RbCl was inactive or had opposite effects. LiCl enhanced the decrease in rectal temperature whereas RbCl was mostly inactive.", "contents": "Effects of lithium and rubidium on antinociception and behaviour in mice. I. Studies on narcotic analgesics and antagonists. The effects of acute and chronic LiCl and RbCl treatments on the antinociception caused by morphine, pethidine, methadone, pentazocine, nalorphine or naloxone were studied in mice using the hot plate and phenylquinone writhing tests. In both tests morphine, pethidine, and methadone caused significant antinociception whereas the antagonistic drugs were almost inactive. In the hot plate test both the 21 day administration of LiCl and the 5 and 21 day administration of RbCl decreased the antinociceptive effect of morphine. The 5 day administration of LiCl increased the antinociceptive effect of pethidine whereas the acute and 5 day administrations of RbCl abolished it. There were no significant or consistent interactions of the ions with the antinociceptive effect of methadone or the antagonistic drugs. In the phenylquinone writhing test the effects of the ions were inconsistent. Especially in the acute experiments where LiCl and RbCl had some effects on the behaviour of the mice treated with the analgesics, LiCl mostly impaired motor coordination and motor activity whereas RbCl was inactive or had opposite effects. LiCl enhanced the decrease in rectal temperature whereas RbCl was mostly inactive."}
{"id": "PMID:10867", "title": "Effects of lithium and rubidium on antinociception and behaviour in mice. II. Studies on three tricyclic antidepressants and pimozide.", "content": "The effects of LiCl and RbCl on the antinociception caused by three antidepressants and pimozide were studied in mice. On the hot plate LiCl given acutely or chronically did not modify the antinociception of any drug although it augmented hypothermia induced by chlorimipramine and occasionally also that caused by desipramine and doxepine, and also caused definitive changes in motor abilities. RbCl given acutely (2.5 mEq/kg) or for 5 or 21 days in tap water (1 g/liter) abolished the antinociception caused by pimozide and when given acutely or for 5 days that of desipramine. In the phenylquinone writhing test LiCl when given for 21 days enhanced the nearly complete antinociception caused by chlorimipramine, doxepine and pimozide. These effects of ions did not seem to be related to changes in body temperature, motor coordination nor motility.", "contents": "Effects of lithium and rubidium on antinociception and behaviour in mice. II. Studies on three tricyclic antidepressants and pimozide. The effects of LiCl and RbCl on the antinociception caused by three antidepressants and pimozide were studied in mice. On the hot plate LiCl given acutely or chronically did not modify the antinociception of any drug although it augmented hypothermia induced by chlorimipramine and occasionally also that caused by desipramine and doxepine, and also caused definitive changes in motor abilities. RbCl given acutely (2.5 mEq/kg) or for 5 or 21 days in tap water (1 g/liter) abolished the antinociception caused by pimozide and when given acutely or for 5 days that of desipramine. In the phenylquinone writhing test LiCl when given for 21 days enhanced the nearly complete antinociception caused by chlorimipramine, doxepine and pimozide. These effects of ions did not seem to be related to changes in body temperature, motor coordination nor motility."}
{"id": "PMID:10869", "title": "Utilization of 35S-thiosulphate and an appraisal of the role of ATP-sulphurylase in chemolithotrophic Thiobacillus ferrooxidans.", "content": "Differentially labelled 35S-thiosulphate was taken up by washed cells of Thiobacillus ferrooxidans which were previously grown on thiosulphate. The uptake was proportional to the biomass over the range 0.5-4.0 mg dry wt. of bacteria and showed typical saturation kinetics with an estimated Km value of 0.5 mM for 35S-thiosulphate. Dithionate and Group VI anions inhibited the uptake, which was under pH control and had a temperature optimum of 50 degrees C. In the absence of thiosulphate, the cells bound 35S-sulphate but the binding did not increase on prolonged incubation and the label could be removed completely by washing with dilute sulphuric acid. Increasing amounts of the label were incorporated from [outer-35S]thiosulphate into cellular materials over a 60-min period, whereas little or no assimilation was observed from either the [inner-35S]thiosulphate or 35S-sulphate. The kinetic properties of the sulphate-activating enzyme ATP-sulphurylase enriched from bacteria grown with either thiosulphate or ferrous-iron were similar although this enzyme has an assimilatory function only when the bacterium is grown with ferrous-iron.", "contents": "Utilization of 35S-thiosulphate and an appraisal of the role of ATP-sulphurylase in chemolithotrophic Thiobacillus ferrooxidans. Differentially labelled 35S-thiosulphate was taken up by washed cells of Thiobacillus ferrooxidans which were previously grown on thiosulphate. The uptake was proportional to the biomass over the range 0.5-4.0 mg dry wt. of bacteria and showed typical saturation kinetics with an estimated Km value of 0.5 mM for 35S-thiosulphate. Dithionate and Group VI anions inhibited the uptake, which was under pH control and had a temperature optimum of 50 degrees C. In the absence of thiosulphate, the cells bound 35S-sulphate but the binding did not increase on prolonged incubation and the label could be removed completely by washing with dilute sulphuric acid. Increasing amounts of the label were incorporated from [outer-35S]thiosulphate into cellular materials over a 60-min period, whereas little or no assimilation was observed from either the [inner-35S]thiosulphate or 35S-sulphate. The kinetic properties of the sulphate-activating enzyme ATP-sulphurylase enriched from bacteria grown with either thiosulphate or ferrous-iron were similar although this enzyme has an assimilatory function only when the bacterium is grown with ferrous-iron."}
{"id": "PMID:10870", "title": "[The activity and properties of adenosine triphosphatase in various swine organs (liver, cerebral and kidney cortex, small intestinal mucosa)].", "content": "Studies into the activity of adenosine triphosphatase (ATPase) in homogenates of liver, cerebral cortex, renal cortex, and mucosa of small intestine of swine have shown differentiated activity patterns, with peak activity developing in the liver. This has been related to a particularly high metabolism performance of the liver in fattening pigs. No difference was found to exist between magnesium activation of ATPase of swine tissue homogenates and that in tissue obtained from ruminants. ATPase which could be activated by sodium and potassium ions and inhibited by ouabain was detectable from cerebral and renal cortex. Sodium and potassium ATPases accounts from some 25 per cent of the total activity. ATPase that could be stimulated by calcium ions was recorded only from liver homogenate. The optimum pH values of ATPase were between 7.5 and 8 in the liver, 9 in mucosa of small intestine, and 9.5 in cerebral and renal cortex.", "contents": "[The activity and properties of adenosine triphosphatase in various swine organs (liver, cerebral and kidney cortex, small intestinal mucosa)]. Studies into the activity of adenosine triphosphatase (ATPase) in homogenates of liver, cerebral cortex, renal cortex, and mucosa of small intestine of swine have shown differentiated activity patterns, with peak activity developing in the liver. This has been related to a particularly high metabolism performance of the liver in fattening pigs. No difference was found to exist between magnesium activation of ATPase of swine tissue homogenates and that in tissue obtained from ruminants. ATPase which could be activated by sodium and potassium ions and inhibited by ouabain was detectable from cerebral and renal cortex. Sodium and potassium ATPases accounts from some 25 per cent of the total activity. ATPase that could be stimulated by calcium ions was recorded only from liver homogenate. The optimum pH values of ATPase were between 7.5 and 8 in the liver, 9 in mucosa of small intestine, and 9.5 in cerebral and renal cortex."}
{"id": "PMID:10871", "title": "[Circulation load test and quality of meat in fattening pigs of known genetic origin].", "content": "102 fattened pigs with known genetic origin were tested on a conveyor-belt 1--4 days before slaughtering. 64 animals run in the first passage in each case 154 m in a 4 minutes (0.64 m/s), compared to it the 38 animals of the second passage run in each case 770 m in 20 minutes. Measurements of heart frequency and breathing and body temperature were taken before and at intervals until 30 minutes after movement. After slaughtering the values of pH, colour and drip loss of the M. longissimus dorsi were measured. It turned out a difference in the meat quality with a high part of PSE-meat in the first passage (36%), caused by season. The criterion \"recovery time of heart action after load\" was able to value the stress susceptibility in dependence on meat quality p.m. Animals with a longer recovery time exhibited a lower pH45 value, a lighter colour and a higher drip loss of meat. But only after a certain stress intensity (2. passage) the assertion was given.", "contents": "[Circulation load test and quality of meat in fattening pigs of known genetic origin]. 102 fattened pigs with known genetic origin were tested on a conveyor-belt 1--4 days before slaughtering. 64 animals run in the first passage in each case 154 m in a 4 minutes (0.64 m/s), compared to it the 38 animals of the second passage run in each case 770 m in 20 minutes. Measurements of heart frequency and breathing and body temperature were taken before and at intervals until 30 minutes after movement. After slaughtering the values of pH, colour and drip loss of the M. longissimus dorsi were measured. It turned out a difference in the meat quality with a high part of PSE-meat in the first passage (36%), caused by season. The criterion \"recovery time of heart action after load\" was able to value the stress susceptibility in dependence on meat quality p.m. Animals with a longer recovery time exhibited a lower pH45 value, a lighter colour and a higher drip loss of meat. But only after a certain stress intensity (2. passage) the assertion was given."}
{"id": "PMID:10872", "title": "[Physico-chemical properties of swine vesicular disease virus].", "content": "Titration of SVDV on primary pig kidney cell cultures revealed a plating efficiency of less than or equal to 0,9 X 10(-3). Concentration and purification of the SVD-Virus propagated on pig kidney cell cultures were done by chloroform treatment, adsorption, differential- and density gradient centrifugation. The following physical parameters were found: SVDV is an isometrical RNA-virus having a diameter of 25,1 +/- 1,0 nm. It is resistent to the action of chloroform, ether and pH. The virus has a sedimentation coefficient of 156 +/- 3S and a bouyant density in CsCl of 1,33 +/- 0,01 g/ml. Within the family of picornaviruses the SVDV belongs to the subgroup of enteroviruses and can be distinguished from the foot-and-mouth disease virus by the difference in pH-sensitivity and bouyant density in CsCl.", "contents": "[Physico-chemical properties of swine vesicular disease virus]. Titration of SVDV on primary pig kidney cell cultures revealed a plating efficiency of less than or equal to 0,9 X 10(-3). Concentration and purification of the SVD-Virus propagated on pig kidney cell cultures were done by chloroform treatment, adsorption, differential- and density gradient centrifugation. The following physical parameters were found: SVDV is an isometrical RNA-virus having a diameter of 25,1 +/- 1,0 nm. It is resistent to the action of chloroform, ether and pH. The virus has a sedimentation coefficient of 156 +/- 3S and a bouyant density in CsCl of 1,33 +/- 0,01 g/ml. Within the family of picornaviruses the SVDV belongs to the subgroup of enteroviruses and can be distinguished from the foot-and-mouth disease virus by the difference in pH-sensitivity and bouyant density in CsCl."}
{"id": "PMID:10874", "title": "Feedback of true heart rate during exposure in vivo. Partial replication with methodological improvement.", "content": "Ten specific phobics improved during a mean of two sessions of experimental treatment by exposure in vivo in a balanced design. Short-term results replicated those of a previous study that self-control of heart rate with the aid of biofeedback significantly reduced heart rate during treatment, but this did not hasten reduction of subjective anxiety, nor of respiratory rate or skin conductance responses. An hour's pretreatment training in self-control of heart rate with the aid of feedback did not enhance the effect. Mere instructions to lower heart rate without feedback had a significant effect during treatment, but the addition of heart rate feedback to instructions significantly augmented the decline in heart rate.", "contents": "Feedback of true heart rate during exposure in vivo. Partial replication with methodological improvement. Ten specific phobics improved during a mean of two sessions of experimental treatment by exposure in vivo in a balanced design. Short-term results replicated those of a previous study that self-control of heart rate with the aid of biofeedback significantly reduced heart rate during treatment, but this did not hasten reduction of subjective anxiety, nor of respiratory rate or skin conductance responses. An hour's pretreatment training in self-control of heart rate with the aid of feedback did not enhance the effect. Mere instructions to lower heart rate without feedback had a significant effect during treatment, but the addition of heart rate feedback to instructions significantly augmented the decline in heart rate."}
{"id": "PMID:10875", "title": "[The influence of partusisten and dilatol on the amino-acid metabolism (author's transl)].", "content": "The betamimetica Dilatol and Partusisten have a glycogenolytic and lipolytic effect on the metabolism. In 21 pregnant women significantly higher concentrations were measured in 9 free amino-acids during intravenous tocolysis with Dilatol. After Partusisten infusion 8 amino-acids were increased. After changing to oral medication of the tocolytica the concentration returned to a normal level again. The clinical significance of these findings is being discussed.", "contents": "[The influence of partusisten and dilatol on the amino-acid metabolism (author's transl)]. The betamimetica Dilatol and Partusisten have a glycogenolytic and lipolytic effect on the metabolism. In 21 pregnant women significantly higher concentrations were measured in 9 free amino-acids during intravenous tocolysis with Dilatol. After Partusisten infusion 8 amino-acids were increased. After changing to oral medication of the tocolytica the concentration returned to a normal level again. The clinical significance of these findings is being discussed."}
{"id": "PMID:10876", "title": "The prognostic value of the non-protein nitrogen (NPN) content in the serum and the cerebrospinal fluid.", "content": "The amounts of total protein and nonprotein nitrogen (NPN), together with the pH were determined in serum and lumbar cerebrospinal fluid (CSF) of controls and comatose patients before and after death. The serum/CSF ratio of NPN was calculated. Under normal conditions the value of this ratio is 1.65. The decrease of this value is a sign of worsening of barrier functions. If the NPN content of the serum and CSF becomes identical, i.e., when the serum/CSF ratio approaches or even equals 1.0, and at the same time the pH decreases in the CSF, then the prognosis is hopeless.", "contents": "The prognostic value of the non-protein nitrogen (NPN) content in the serum and the cerebrospinal fluid. The amounts of total protein and nonprotein nitrogen (NPN), together with the pH were determined in serum and lumbar cerebrospinal fluid (CSF) of controls and comatose patients before and after death. The serum/CSF ratio of NPN was calculated. Under normal conditions the value of this ratio is 1.65. The decrease of this value is a sign of worsening of barrier functions. If the NPN content of the serum and CSF becomes identical, i.e., when the serum/CSF ratio approaches or even equals 1.0, and at the same time the pH decreases in the CSF, then the prognosis is hopeless."}
{"id": "PMID:10877", "title": "[Kates forefoot arthroplasty (author's transl)].", "content": "In a series of 93 forefoot arthroplasties (71 of them followed up), the majority of the cases showed good results of Kates' procedure. The most frequent sources of errors are inadequate treatment of the plantar skin and the formation of steps in the line of resection of the mid-tarsal bones. Rheumatic and degenerative forefoot deformities are equally well suited for this procedure. Forefoot deformities combined with pes equinus appear to be less suitable.", "contents": "[Kates forefoot arthroplasty (author's transl)]. In a series of 93 forefoot arthroplasties (71 of them followed up), the majority of the cases showed good results of Kates' procedure. The most frequent sources of errors are inadequate treatment of the plantar skin and the formation of steps in the line of resection of the mid-tarsal bones. Rheumatic and degenerative forefoot deformities are equally well suited for this procedure. Forefoot deformities combined with pes equinus appear to be less suitable."}
{"id": "PMID:10882", "title": "Evaluation of intrinsic sympathomimetic activity of beta-adrenoceptor blocking drugs in the treatment of patients with angina pectoris.", "content": "Beta-adrenoceptor blocking drugs with intrinsic sympathomimetic activity (ISA) may be less effective in the treatment of patients with angina pectoris than some others that lack this property. A review of 14 trials comparing beta-adrenoceptor blocking drug with ISA and those without ISA in angina pectoris has been made. The overall picture emerges from both acute and chronic studies using subjective and objective endpoints, that there is no striking difference in effectiveness between the two kinds of beta-adrenoceptor blocking drugs. The one exception is pindolol (a drug with ISA) which, at higher doses, has been shown to be consistently worse than propranolol (a drug without ISA). The reasons for the similarity between propranolol and other bets-blocking drugs with ISA in the trials cited are either that the trial design was defective (the trials were mainly fixed dose comparisons) or that the stimulant effects of those drugs with ISA is not of sufficient magnitude to make a difference. It is suggested that further carefully constructed clinical trials should be carried out before the second reason can be accepted.", "contents": "Evaluation of intrinsic sympathomimetic activity of beta-adrenoceptor blocking drugs in the treatment of patients with angina pectoris. Beta-adrenoceptor blocking drugs with intrinsic sympathomimetic activity (ISA) may be less effective in the treatment of patients with angina pectoris than some others that lack this property. A review of 14 trials comparing beta-adrenoceptor blocking drug with ISA and those without ISA in angina pectoris has been made. The overall picture emerges from both acute and chronic studies using subjective and objective endpoints, that there is no striking difference in effectiveness between the two kinds of beta-adrenoceptor blocking drugs. The one exception is pindolol (a drug with ISA) which, at higher doses, has been shown to be consistently worse than propranolol (a drug without ISA). The reasons for the similarity between propranolol and other bets-blocking drugs with ISA in the trials cited are either that the trial design was defective (the trials were mainly fixed dose comparisons) or that the stimulant effects of those drugs with ISA is not of sufficient magnitude to make a difference. It is suggested that further carefully constructed clinical trials should be carried out before the second reason can be accepted."}
{"id": "PMID:10883", "title": "Characterization of hemoglobin Burke [beta 107 (G9) Gly replaced by Arg].", "content": "Hb Burke [beta 107 (G9) Gly replaced by Arg] was discovered in a young woman with hemolytic anemia. A substitution in this position has not been previously reported either in the human beta-chain or in any of the animal beta-chains so far sequenced. The abnormal hemoglobin shows heat instability and a lowered oxygen affinity. The substitution of a large charged arginine residue for the small glycine residue in the G helix next to a heme contact (Leu-106) may be responsible for these effects. Hb Burke is compared with five other hemoglobins having Gly-Arg substitutions in other parts of the molecule.", "contents": "Characterization of hemoglobin Burke [beta 107 (G9) Gly replaced by Arg]. Hb Burke [beta 107 (G9) Gly replaced by Arg] was discovered in a young woman with hemolytic anemia. A substitution in this position has not been previously reported either in the human beta-chain or in any of the animal beta-chains so far sequenced. The abnormal hemoglobin shows heat instability and a lowered oxygen affinity. The substitution of a large charged arginine residue for the small glycine residue in the G helix next to a heme contact (Leu-106) may be responsible for these effects. Hb Burke is compared with five other hemoglobins having Gly-Arg substitutions in other parts of the molecule."}
{"id": "PMID:10884", "title": "Genetically defined peptidases of maize. I. Biochemical characterization of allelic and nonallelic forms.", "content": "A number of biochemical properties have been investigated for both allelic and nonallelic forms of maize peptidases. Four aminopeptidases exist in maize (LAP-A, LAP-B, LAP-C, and LAP-D) and are the products of four diallelic loci. The aminopeptidases fall into two biochemical groups on the basis of these studies. LAP-A and LAP-D have comparatively low apparent Km (Kapp) values for arginine-naphthylamide derivatives and high velocities for arginine-naphthyl-amide and lysine-naphthylamide. LAP-B and LAP-C, on the other hand, have lower Kapp values for leucine-naphthylamide and higher velocities for nonpolar amino acid-naphthylamides than for arginine-naphthylamide. LAP-A and LAP-D are also relatively more heat stable than LAP-B and LAP-C and have somewhat higher molecular weights (71,500) than LAP-B and LAP-C (63,500). In determining molecular weights of the peptidases, use was made of their differential substrate specificities toward amino acid-naphthylamides. Some properties of genetically defined maize endopeptidase are also presented. Maize endopeptidase is inhibited by the sulfhydryl reagents N-ethylmaleimide and p-chloromercuribenzoate (pCMB), and by tosyl lysine chloromethyl ketone, Maize aminopeptidase activity is inhibited by N-ethylmaleimide, pCMB, and EDTA (ethylenediamine tetraacetic acid).", "contents": "Genetically defined peptidases of maize. I. Biochemical characterization of allelic and nonallelic forms. A number of biochemical properties have been investigated for both allelic and nonallelic forms of maize peptidases. Four aminopeptidases exist in maize (LAP-A, LAP-B, LAP-C, and LAP-D) and are the products of four diallelic loci. The aminopeptidases fall into two biochemical groups on the basis of these studies. LAP-A and LAP-D have comparatively low apparent Km (Kapp) values for arginine-naphthylamide derivatives and high velocities for arginine-naphthyl-amide and lysine-naphthylamide. LAP-B and LAP-C, on the other hand, have lower Kapp values for leucine-naphthylamide and higher velocities for nonpolar amino acid-naphthylamides than for arginine-naphthylamide. LAP-A and LAP-D are also relatively more heat stable than LAP-B and LAP-C and have somewhat higher molecular weights (71,500) than LAP-B and LAP-C (63,500). In determining molecular weights of the peptidases, use was made of their differential substrate specificities toward amino acid-naphthylamides. Some properties of genetically defined maize endopeptidase are also presented. Maize endopeptidase is inhibited by the sulfhydryl reagents N-ethylmaleimide and p-chloromercuribenzoate (pCMB), and by tosyl lysine chloromethyl ketone, Maize aminopeptidase activity is inhibited by N-ethylmaleimide, pCMB, and EDTA (ethylenediamine tetraacetic acid)."}
{"id": "PMID:10885", "title": "Aryl hydrocarbon hydroxylase and 16alpha-hydroxylase in cultured human lymphocytes.", "content": "Aryl hydrocarbon hydroxylase and 16alpha-hydroxylase were examined in intact, cultured human lymphocytes. The two microsomal mixed-function oxygenases had different pH optima and showed competitive inhibition for enzyme induction and activity. Population distributions were lognormal for both enzymes, giving apparent evidence for polygenic control. Induced levels of AHH were slightly higher among first-order relatives of lung or colon cancer patients than in the control group. The correlation coefficient (r) for AHH and SAH coinducibility was -0.08, indicating no correlation and suggesting the absence of association between the two enzymes in man.", "contents": "Aryl hydrocarbon hydroxylase and 16alpha-hydroxylase in cultured human lymphocytes. Aryl hydrocarbon hydroxylase and 16alpha-hydroxylase were examined in intact, cultured human lymphocytes. The two microsomal mixed-function oxygenases had different pH optima and showed competitive inhibition for enzyme induction and activity. Population distributions were lognormal for both enzymes, giving apparent evidence for polygenic control. Induced levels of AHH were slightly higher among first-order relatives of lung or colon cancer patients than in the control group. The correlation coefficient (r) for AHH and SAH coinducibility was -0.08, indicating no correlation and suggesting the absence of association between the two enzymes in man."}
{"id": "PMID:10886", "title": "Large-scale purification and characterization of dihydrofolate reductase from a methotrexate-resistant strain of Lactobacillus casei.", "content": "Dihydrofolate reductase has been purified from a methotrexate-resistant strain of Lactobacillus casei NCB 6375. By careful attention to growth conditions, up to 2.5 g of enzyme is obtained from a 400 litre culture. The purification procedure, involving poly-ethyleneimine treatment, DEAE-cellulose chromatography and affinity chromatography on methotrexate-aminohexyl-Sepharose, operates on the gram scale, with overall yields of 50-60%. Elution of the affinity column by reverse (upward) flow was used, as it led to recovery of the enzyme in a much smaller volume. The enzyme obtained appears to be more than 98% pure, as judged by gel electrophoresis, isoelectric focusing, and gel filtration. It has a mol.wt. of approx. 17900 and a turnover number of 4s-1 (50mM-triethanolamine/400mM-KCl, pH 7.2, 25 degrees C) with dihydrofolate and NADPH as substrates. The turnover number for folate is 0.02s-1. Michaelis constants for a variety of substrates have been measured by using a new fluorimetric assay (0.36 muM-dihydrofolate; 0.78 muM-NADPH), and binding constants determined by using the quenching of protein fluorescence (dihydrofolate, 2.25 X 10(6)M-1; NADPH, greater than 10(8)M-1). The pH/activity profile shows a single maximum at pH 7.3; at this pH, marked activation by 0.5M-NaCl is observed.", "contents": "Large-scale purification and characterization of dihydrofolate reductase from a methotrexate-resistant strain of Lactobacillus casei. Dihydrofolate reductase has been purified from a methotrexate-resistant strain of Lactobacillus casei NCB 6375. By careful attention to growth conditions, up to 2.5 g of enzyme is obtained from a 400 litre culture. The purification procedure, involving poly-ethyleneimine treatment, DEAE-cellulose chromatography and affinity chromatography on methotrexate-aminohexyl-Sepharose, operates on the gram scale, with overall yields of 50-60%. Elution of the affinity column by reverse (upward) flow was used, as it led to recovery of the enzyme in a much smaller volume. The enzyme obtained appears to be more than 98% pure, as judged by gel electrophoresis, isoelectric focusing, and gel filtration. It has a mol.wt. of approx. 17900 and a turnover number of 4s-1 (50mM-triethanolamine/400mM-KCl, pH 7.2, 25 degrees C) with dihydrofolate and NADPH as substrates. The turnover number for folate is 0.02s-1. Michaelis constants for a variety of substrates have been measured by using a new fluorimetric assay (0.36 muM-dihydrofolate; 0.78 muM-NADPH), and binding constants determined by using the quenching of protein fluorescence (dihydrofolate, 2.25 X 10(6)M-1; NADPH, greater than 10(8)M-1). The pH/activity profile shows a single maximum at pH 7.3; at this pH, marked activation by 0.5M-NaCl is observed."}
{"id": "PMID:10887", "title": "Determination of the mechanism and kinetic constants for hog kidney gamma-glutamyltransferase.", "content": "The initial-velocity kinetics of hog kidney gamma-glutamyltransferase were studied. Glutamate gamma-(4-nitroanilide) and its 3-carboxy derivative, glutamate gamma-(3-carboxy-4-nitroanilide), served as gamma-glutamyl donors, and glycylglycine as an acceptor. Reaction products were identified by paper chromatography and amino acid analysis. Inhibited Ping Pong mechanisms and a comprehensive initial- velocity expression were developed which account for the observed simultaneous gamma-glutamyl transfer and autotransfer, competitive inhibition by glycylglycine, and non-competitive inhibition by the carboxy donor. The validity of the proposed Ping Pong mechanisms are supported by enzyme-velocity data obtained with constant ratios of acceptor to donor concentrations. Kinetic constants were determined by a non-linear regression analysis. With glutamate gamma-(4-nitroanilide) as the donor, Michaelis constants for the donor, acceptor and donor-acting-as-acceptor are 1.87, 24.9, and 2.08 mM respectively. With glutamate gamma-(3-carboxy-4-nitroanilide) as the donor, these Michaelis constants are 1.63, 16.6, and 12.3 mM. Glyclyglycine competitive inhibition constants with the parent donor and its carboxy derivative are 275 and 205 mM respectively; the non-competitive inhibition constant of the carboxy donor is 34 mM.", "contents": "Determination of the mechanism and kinetic constants for hog kidney gamma-glutamyltransferase. The initial-velocity kinetics of hog kidney gamma-glutamyltransferase were studied. Glutamate gamma-(4-nitroanilide) and its 3-carboxy derivative, glutamate gamma-(3-carboxy-4-nitroanilide), served as gamma-glutamyl donors, and glycylglycine as an acceptor. Reaction products were identified by paper chromatography and amino acid analysis. Inhibited Ping Pong mechanisms and a comprehensive initial- velocity expression were developed which account for the observed simultaneous gamma-glutamyl transfer and autotransfer, competitive inhibition by glycylglycine, and non-competitive inhibition by the carboxy donor. The validity of the proposed Ping Pong mechanisms are supported by enzyme-velocity data obtained with constant ratios of acceptor to donor concentrations. Kinetic constants were determined by a non-linear regression analysis. With glutamate gamma-(4-nitroanilide) as the donor, Michaelis constants for the donor, acceptor and donor-acting-as-acceptor are 1.87, 24.9, and 2.08 mM respectively. With glutamate gamma-(3-carboxy-4-nitroanilide) as the donor, these Michaelis constants are 1.63, 16.6, and 12.3 mM. Glyclyglycine competitive inhibition constants with the parent donor and its carboxy derivative are 275 and 205 mM respectively; the non-competitive inhibition constant of the carboxy donor is 34 mM."}
{"id": "PMID:10888", "title": "Organ distribution of rat histidine-pyruvate aminotransferase isoenzymes.", "content": "The organ distribution of rat histidine-pyruvate aminotransferase isoenzymes 1 and 2 was examined by using an isoelectric-focusing technique. Isoenzyme 1 (pI8.0) is present only in the liver and its activity is increased by the injection of glucagon, whereas isoenzyme 2 (pI5.2) is distributed in all tissues (liver, kidney, brain and heart) tested, and is not affected by glucagon injection. Isoenzyme 2 of the liver, kidney, brain and heart was purified by the same procedure and characterized. Isoenzyme 2 preparations from these four tissues were nearly identical in physical and enzymic properties. These properties differed from those previously found for the highly purified isoenzyme 1 preparation of rat liver. Isoenzyme 2 was active with pyruvate but not with 2-oxoglutarate as amino acceptor. Amino donors were effective in the following order of activity: tyrosine greater than histidine greater than phenylalanine greater than kynurenine greater than tryptophan. Very little activity was found with 5-hydroxytryptophan. The apparent Km for histidine was about 0.45 mM. The Km for pyruvate was about 4.5 mM with histidine as amino donor. The amino-transferase activities of isoenzyme 2 towards phenylalanine and tyrosine were inhibited by histidine. The ratio of aminotransferase activities towards these three amino acids was constant through gel filtration, electrophoresis, isoelectric focusing and sucrose-density-gradient centrifugation of the purified isoenzyme 2 preparations. These results suggest that these three activities are properties of the same enzyme protein. Sephadex G-150 gel filtration and sucrose-density-gradient centrifugation yielded mol.wts. of approx. 95000 and 92000 respectively. The pH optimum was between 9.0 and 9.3.", "contents": "Organ distribution of rat histidine-pyruvate aminotransferase isoenzymes. The organ distribution of rat histidine-pyruvate aminotransferase isoenzymes 1 and 2 was examined by using an isoelectric-focusing technique. Isoenzyme 1 (pI8.0) is present only in the liver and its activity is increased by the injection of glucagon, whereas isoenzyme 2 (pI5.2) is distributed in all tissues (liver, kidney, brain and heart) tested, and is not affected by glucagon injection. Isoenzyme 2 of the liver, kidney, brain and heart was purified by the same procedure and characterized. Isoenzyme 2 preparations from these four tissues were nearly identical in physical and enzymic properties. These properties differed from those previously found for the highly purified isoenzyme 1 preparation of rat liver. Isoenzyme 2 was active with pyruvate but not with 2-oxoglutarate as amino acceptor. Amino donors were effective in the following order of activity: tyrosine greater than histidine greater than phenylalanine greater than kynurenine greater than tryptophan. Very little activity was found with 5-hydroxytryptophan. The apparent Km for histidine was about 0.45 mM. The Km for pyruvate was about 4.5 mM with histidine as amino donor. The amino-transferase activities of isoenzyme 2 towards phenylalanine and tyrosine were inhibited by histidine. The ratio of aminotransferase activities towards these three amino acids was constant through gel filtration, electrophoresis, isoelectric focusing and sucrose-density-gradient centrifugation of the purified isoenzyme 2 preparations. These results suggest that these three activities are properties of the same enzyme protein. Sephadex G-150 gel filtration and sucrose-density-gradient centrifugation yielded mol.wts. of approx. 95000 and 92000 respectively. The pH optimum was between 9.0 and 9.3."}
{"id": "PMID:10889", "title": "The asymmetric distribution of enzymic activity between the six subunits of bovine liver glutamate dehydrogenase. Use of D- and L-glutamyl alpha-chloromethyl ketones (4-amino-6-chloro-5-oxohexanoic acid.", "content": "A method for the preparation of D- and L-glutamyl alpha-chloromethyl ketones (4-amino-6-chloro-5-oxohexanoic acid) is described. These chloromethyl ketones irreversibly inactivated bovine glutamate dehydrogenase, whereas several other related compounds had no adverse effect on the activity of the enzyme. The inactivation process was shown to be due to the modification of lysine-126. The time-courses for the inactivation and the incorporation of radioactivity from tritiated L-glutamyl alpha-chloromethyl ketone into the glutamate dehydrogenase were biphasic. The results were interpreted to suggest the involvement of 'negative co-operative' interactions in the reactivity of lysine-126. From the cumulative evidence it is argued that the first subunit of the enzyme, which takes part in catalysis, makes the largest, and the last the smallest, contribution to the overall catalysis. It is emphasized that three of the six subunits of the enzyme may possess as much as 80% of the total activity of bovine glutamate dehydrogenase.", "contents": "The asymmetric distribution of enzymic activity between the six subunits of bovine liver glutamate dehydrogenase. Use of D- and L-glutamyl alpha-chloromethyl ketones (4-amino-6-chloro-5-oxohexanoic acid. A method for the preparation of D- and L-glutamyl alpha-chloromethyl ketones (4-amino-6-chloro-5-oxohexanoic acid) is described. These chloromethyl ketones irreversibly inactivated bovine glutamate dehydrogenase, whereas several other related compounds had no adverse effect on the activity of the enzyme. The inactivation process was shown to be due to the modification of lysine-126. The time-courses for the inactivation and the incorporation of radioactivity from tritiated L-glutamyl alpha-chloromethyl ketone into the glutamate dehydrogenase were biphasic. The results were interpreted to suggest the involvement of 'negative co-operative' interactions in the reactivity of lysine-126. From the cumulative evidence it is argued that the first subunit of the enzyme, which takes part in catalysis, makes the largest, and the last the smallest, contribution to the overall catalysis. It is emphasized that three of the six subunits of the enzyme may possess as much as 80% of the total activity of bovine glutamate dehydrogenase."}
{"id": "PMID:10890", "title": "Guanylate cyclase. Subcellular distribution in cardiac muscle, skeletal muscle, cerebral cortex and liver.", "content": "1. Guanylate cyclase of every fraction studied showed an absolute requirement for Mn2+ ions for optimal activity; with Mg2+ or Ca2+ reaction was barely detectable. Triton X-100 stimulated the particulate enzyme much more than the supernatant enzyme and solubilized the particulate-enzyme activity. 2. Substantial amounts of guanylate cyclase were recovered with the washed particulate fractions of cardiac muscle (63-98%), skeletal muscle (77-93%), cerebral cortex (62-88%) and liver (60-75%) of various species. The supernatants of these tissues contained 7-38% of total activities. In frog heart, the bulk of guanylate cyclase was present in the supernatant fluid. 3. Plasma-membrane fractions contained 26, 21, 22 and 40% respectively of the total homogenate guanylate cyclase activities present in skeletal muscle (rabbit), cardiac muscle (guinea pig), liver (rat) and cerebral cortex (rat). In each case, the specific activity of this enzyme in plasma membranes showed a five- to ten-fold enrichment when compared with homogenate specific activity. 4. These results suggest that guanylate cyclase, like adenylate cyclase, and ouabain-sensitive Na+ + K+-dependent ATPase (adenosine triphosphatase), is associated with the surface membranes of cardiac muscle, skeletal muscle, liver and cerebral cortex; however, considerable activities are also present in the supernatant fractions of these tissues which contain very little adenylate cyclase or ouabain-sensitive Na+ + K+-dependent ATPase activities.", "contents": "Guanylate cyclase. Subcellular distribution in cardiac muscle, skeletal muscle, cerebral cortex and liver. 1. Guanylate cyclase of every fraction studied showed an absolute requirement for Mn2+ ions for optimal activity; with Mg2+ or Ca2+ reaction was barely detectable. Triton X-100 stimulated the particulate enzyme much more than the supernatant enzyme and solubilized the particulate-enzyme activity. 2. Substantial amounts of guanylate cyclase were recovered with the washed particulate fractions of cardiac muscle (63-98%), skeletal muscle (77-93%), cerebral cortex (62-88%) and liver (60-75%) of various species. The supernatants of these tissues contained 7-38% of total activities. In frog heart, the bulk of guanylate cyclase was present in the supernatant fluid. 3. Plasma-membrane fractions contained 26, 21, 22 and 40% respectively of the total homogenate guanylate cyclase activities present in skeletal muscle (rabbit), cardiac muscle (guinea pig), liver (rat) and cerebral cortex (rat). In each case, the specific activity of this enzyme in plasma membranes showed a five- to ten-fold enrichment when compared with homogenate specific activity. 4. These results suggest that guanylate cyclase, like adenylate cyclase, and ouabain-sensitive Na+ + K+-dependent ATPase (adenosine triphosphatase), is associated with the surface membranes of cardiac muscle, skeletal muscle, liver and cerebral cortex; however, considerable activities are also present in the supernatant fractions of these tissues which contain very little adenylate cyclase or ouabain-sensitive Na+ + K+-dependent ATPase activities."}
{"id": "PMID:10891", "title": "Properties of particulate, membrane-associated and soluble guanylate cyclase from cardiac muscle, skeletal muscle, cerebral cortex and liver.", "content": "1. Guanylate cyclase of washed particles and plasma membranes showed S-shaped progress curves when titrated with either GTP or Mn2+ ions; similar results were obtained with Triton X-100-solubilized enzyme preparation from washed particles. Hill plots of these data revealed multiple metal-nucleotide and free-metal binding sites. 2. Guanylate cyclase of supernatant fractions displayed typical Michaelis-Menten properties when enzyme required excess of (free) Mn2+ (over GTP) for maximal activities; Ka (free Mn2+) was about 0.15-0.25 mM at subsaturating concentrations of GTP. 4 MnATP, MnADP, and MnGDP were found to increase the activities of both particulate and superantant enzyme, when MnGTP concentration was below saturation and free Mn2+ ion concentration was low (less than 100 muM); MnATP (50muM-1 mM) inhibited both these activities at high free Mn2+ concentration (1.5 mM) and inhibition of the particulate enzyme was greater than that of supernatant enzyme. 5. Ca2+ ions stimulated supernatant-enzyme activity; the stimulatory concentration of Ca2+ ions depended on the concentration of Mn2+ and GTP. 6. A modest stimulation of particulate guanylate cyclase by pyrophosphate (0.02-1 mM) was observed; the pyrophosphate effect appeared to be competitive with respect to GTP. At a higher concentration (2 mM), pyrophosphate produced a marked inhibition of particulate enzyme; the nature of inhibitory effect appeared complex. 7. Inorganic salts (e.g. NaCl, KCl, LiBr, NaF) produced inhibition of particulate enzyme; the degree of inhibition of Triton X-100-stimulated activity was less than that of unstimulated activity. 9. Treatment of sarcolemmal or microsomal membranes with either phospholipase C or trypsin decreased, whereas phospholipase A increased, the activity of guanylate cyclase.", "contents": "Properties of particulate, membrane-associated and soluble guanylate cyclase from cardiac muscle, skeletal muscle, cerebral cortex and liver. 1. Guanylate cyclase of washed particles and plasma membranes showed S-shaped progress curves when titrated with either GTP or Mn2+ ions; similar results were obtained with Triton X-100-solubilized enzyme preparation from washed particles. Hill plots of these data revealed multiple metal-nucleotide and free-metal binding sites. 2. Guanylate cyclase of supernatant fractions displayed typical Michaelis-Menten properties when enzyme required excess of (free) Mn2+ (over GTP) for maximal activities; Ka (free Mn2+) was about 0.15-0.25 mM at subsaturating concentrations of GTP. 4 MnATP, MnADP, and MnGDP were found to increase the activities of both particulate and superantant enzyme, when MnGTP concentration was below saturation and free Mn2+ ion concentration was low (less than 100 muM); MnATP (50muM-1 mM) inhibited both these activities at high free Mn2+ concentration (1.5 mM) and inhibition of the particulate enzyme was greater than that of supernatant enzyme. 5. Ca2+ ions stimulated supernatant-enzyme activity; the stimulatory concentration of Ca2+ ions depended on the concentration of Mn2+ and GTP. 6. A modest stimulation of particulate guanylate cyclase by pyrophosphate (0.02-1 mM) was observed; the pyrophosphate effect appeared to be competitive with respect to GTP. At a higher concentration (2 mM), pyrophosphate produced a marked inhibition of particulate enzyme; the nature of inhibitory effect appeared complex. 7. Inorganic salts (e.g. NaCl, KCl, LiBr, NaF) produced inhibition of particulate enzyme; the degree of inhibition of Triton X-100-stimulated activity was less than that of unstimulated activity. 9. Treatment of sarcolemmal or microsomal membranes with either phospholipase C or trypsin decreased, whereas phospholipase A increased, the activity of guanylate cyclase."}
{"id": "PMID:10892", "title": "Changes in conformation of reduced cytochrome c in neutral aqueous solution.", "content": "In neutral aqueous solution, high concentrations of alcohols perturb cytochrome c in such a way that reduction by means of ionizing radiation results in the formation of abnormal conformers of ferrocytochrome c resembling those previously seen on reduction in alkaline solution. These relax to normal ferrocytochrome c in about 0.1 s.", "contents": "Changes in conformation of reduced cytochrome c in neutral aqueous solution. In neutral aqueous solution, high concentrations of alcohols perturb cytochrome c in such a way that reduction by means of ionizing radiation results in the formation of abnormal conformers of ferrocytochrome c resembling those previously seen on reduction in alkaline solution. These relax to normal ferrocytochrome c in about 0.1 s."}
{"id": "PMID:10893", "title": "The effects of diphenyleneiodonium and of 2,4-dichlorodiphenyleneiodonium on mitochondrial reactions. Mechanism of the inhibition of oxygen uptake as a consequence of the catalysis of the chloride/hydroxyl-ion exchange.", "content": "1. Increasing the substrate concentration only decreased the inhibition of mitochondrial oxidations by diphenyleneiodonium or by 2,4-dichlorophenyleneiodonium by a small amount. 2. Diphenyleneiodonium and 2,4-dichlorodiphenyleneiodonium lowered the amounts of succinate, citrate and glutamate accumulated in the matrix of mitochondria in the presence of Cl-, but not in its absences. 2,4-Dichlorodiphenyleneiodonium decreased the accumulation of substrates by mitochondria oxidizing glycerol 3-phosphate. 3. Diphenyleneiodonium caused an alkalinization of the medium with an anaerobic suspension of mitochondria, which was only partly reversed by Triton X-100. 4. The rate of proton extrusion by mitochondria oxidizing succinate was not altered by diphenyleneiodonium or by 2,4-dichlorodiphenyleneiodium, although the rate of decay of proton pulses was increased. 5. 2,4-Dichlorodiphenyleneiodonium shifted the pH optimum for succinate oxidation by intact mitochondria from pH 7.2 to 8.0, whereas there was no effect on that of freeze-thawed mitochondria, which was pH 8.0. 6. The concentration of 2,4-dichlorophenyleneiodonium required to inhibit respiration by 50% is less the higher the absolute rate of oxygen uptake. 7. EDTA, but not EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid] increased the inhibition of respiration by diphenyleneiodonium, 2,4-dichlorodiphenyleneiodonium and by tri-n-propyltin. 8. It is concluded that diphenyleneiodonium and 2,4-dichlorodiphenyleneiodonium limit respiration in Cl--containing medium by causing an acidification of the matrix, and that there are pH-sensitive sites in the respiratory chain between NADH and succinate, and between succinate and cytochrome c.", "contents": "The effects of diphenyleneiodonium and of 2,4-dichlorodiphenyleneiodonium on mitochondrial reactions. Mechanism of the inhibition of oxygen uptake as a consequence of the catalysis of the chloride/hydroxyl-ion exchange. 1. Increasing the substrate concentration only decreased the inhibition of mitochondrial oxidations by diphenyleneiodonium or by 2,4-dichlorophenyleneiodonium by a small amount. 2. Diphenyleneiodonium and 2,4-dichlorodiphenyleneiodonium lowered the amounts of succinate, citrate and glutamate accumulated in the matrix of mitochondria in the presence of Cl-, but not in its absences. 2,4-Dichlorodiphenyleneiodonium decreased the accumulation of substrates by mitochondria oxidizing glycerol 3-phosphate. 3. Diphenyleneiodonium caused an alkalinization of the medium with an anaerobic suspension of mitochondria, which was only partly reversed by Triton X-100. 4. The rate of proton extrusion by mitochondria oxidizing succinate was not altered by diphenyleneiodonium or by 2,4-dichlorodiphenyleneiodium, although the rate of decay of proton pulses was increased. 5. 2,4-Dichlorodiphenyleneiodonium shifted the pH optimum for succinate oxidation by intact mitochondria from pH 7.2 to 8.0, whereas there was no effect on that of freeze-thawed mitochondria, which was pH 8.0. 6. The concentration of 2,4-dichlorophenyleneiodonium required to inhibit respiration by 50% is less the higher the absolute rate of oxygen uptake. 7. EDTA, but not EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid] increased the inhibition of respiration by diphenyleneiodonium, 2,4-dichlorodiphenyleneiodonium and by tri-n-propyltin. 8. It is concluded that diphenyleneiodonium and 2,4-dichlorodiphenyleneiodonium limit respiration in Cl--containing medium by causing an acidification of the matrix, and that there are pH-sensitive sites in the respiratory chain between NADH and succinate, and between succinate and cytochrome c."}
{"id": "PMID:10894", "title": "Properties and developmental regulation of an alpha-d-galactosidase from Dictyostelium discoideum.", "content": "An alpha-D-galactosidase was detected in cells of the cellular slime mould, Dictyostelium discoideum, at all stages of development. Its specific activity was highest during early development (interphase), and this accumulation of enzyme appears to require protein synthesis de novo. Its subcellular distribution differs from that of other D. discoideum glycosidases, since most activity was recovered in the soluble fraction. No evidence was obtained for more than one isoenzymic form after subjection of extracts to electrophoresis and various chromatographic procedures. It is excreted from the cell during development, but no evidence was found for an extracellular function for the enzyme.", "contents": "Properties and developmental regulation of an alpha-d-galactosidase from Dictyostelium discoideum. An alpha-D-galactosidase was detected in cells of the cellular slime mould, Dictyostelium discoideum, at all stages of development. Its specific activity was highest during early development (interphase), and this accumulation of enzyme appears to require protein synthesis de novo. Its subcellular distribution differs from that of other D. discoideum glycosidases, since most activity was recovered in the soluble fraction. No evidence was obtained for more than one isoenzymic form after subjection of extracts to electrophoresis and various chromatographic procedures. It is excreted from the cell during development, but no evidence was found for an extracellular function for the enzyme."}
{"id": "PMID:10895", "title": "Adenylate cyclase, guanylate cyclase and cyclic nucleotide phosphodiesterases of guinea-pig cardiac sarcolemma.", "content": "1. The activities of the enzymes involved in the metabolism of cyclic nucleotides were studied in sarcolemma prepared front guinea-pig heart ventricle; the enzyme activities reported here were linear under the assay conditions. 2. Adenylate cyclase was maximally activated by 3mM-NaF; NaF increased the Km for ATP (from 0.042 to 0.19 mM) but decreased the Ka for Mg2+ (from 2.33 to 0.9 mM). In the presence of saturating Mg2+ (15 mM), Mn2+ enhanced adenylate cyclase, whereas Co2+ was inhibitory. beta-Adrenergic amines (10-50 muM) stimulated adenylate cyclase (38+/-2%). When added to the assay mixture, guanyl nucleotides (GTP and its analogue, guanylyl imidophosphate) stimulated basal enzyme activity and enhanced the stimulation by isoproterenol. By contrast, preincubation of sarcolemma with guanylyl imidodiphosphate stimulated the formation of an 'activated' form of the enzyme, which did not reveal increased hormonal sensitivity. 3. The guanylate cyclase present in the membranes as well as in the Triton X-100-solubilized extract of membranes exhibited a Ka for Mn 2+ of 0.3 mM; Mn2+ in excess of GTP was required for maximal activity. Solubilized guanylate cyclase was activated by Mg2+ only in the presence of low Mn2+ concentrations; Ca2+ was inhibitory both in the absence and presence of low Mn2+. Acetylcholine as well as carbamolycholine stimulated membrane-bound guanylate cyclase. 4. Cylic nucleotide phosphodiesterase activities of sarcolemma exhibited both high-and low-Km forms with cyclic AMP and with cyclic GMP as substrate. Ca2+ ions increased the Vmax. of the cyclic GMP-dependent enzyme.", "contents": "Adenylate cyclase, guanylate cyclase and cyclic nucleotide phosphodiesterases of guinea-pig cardiac sarcolemma. 1. The activities of the enzymes involved in the metabolism of cyclic nucleotides were studied in sarcolemma prepared front guinea-pig heart ventricle; the enzyme activities reported here were linear under the assay conditions. 2. Adenylate cyclase was maximally activated by 3mM-NaF; NaF increased the Km for ATP (from 0.042 to 0.19 mM) but decreased the Ka for Mg2+ (from 2.33 to 0.9 mM). In the presence of saturating Mg2+ (15 mM), Mn2+ enhanced adenylate cyclase, whereas Co2+ was inhibitory. beta-Adrenergic amines (10-50 muM) stimulated adenylate cyclase (38+/-2%). When added to the assay mixture, guanyl nucleotides (GTP and its analogue, guanylyl imidophosphate) stimulated basal enzyme activity and enhanced the stimulation by isoproterenol. By contrast, preincubation of sarcolemma with guanylyl imidodiphosphate stimulated the formation of an 'activated' form of the enzyme, which did not reveal increased hormonal sensitivity. 3. The guanylate cyclase present in the membranes as well as in the Triton X-100-solubilized extract of membranes exhibited a Ka for Mn 2+ of 0.3 mM; Mn2+ in excess of GTP was required for maximal activity. Solubilized guanylate cyclase was activated by Mg2+ only in the presence of low Mn2+ concentrations; Ca2+ was inhibitory both in the absence and presence of low Mn2+. Acetylcholine as well as carbamolycholine stimulated membrane-bound guanylate cyclase. 4. Cylic nucleotide phosphodiesterase activities of sarcolemma exhibited both high-and low-Km forms with cyclic AMP and with cyclic GMP as substrate. Ca2+ ions increased the Vmax. of the cyclic GMP-dependent enzyme."}
{"id": "PMID:10937", "title": "Maternal blood-gases, PAo2--Pao2), hysiological shunt and VD/VT in normal pregnancy.", "content": "Serial measurements of maternal blood-gases, alveolar-to-arterial oxygen tension difference (PAO2--PaO), calculated pulmonary venous admixture (physiological shunt), deadspace/tidal volume ratio (VD/VT), and respiratory minute volume have been made in a carefully selected group of normal pregnant patients at 12, 24, 32 and 38 weeks of gestation and 5 weeks after delivery. All measurements were made in the semi-recumbent position with a left lateral pelvic tilt. Mean arterial PO2 was consistently greater than 100 mm Hg throughout pregnancy, although the value decreased from 106.4 mm Hg at 12 weeks of gestation to 101.8 mm Hg at the 38th week. Despite this decrease there was no change in (PAO2--PaO2) VD/VT, or percentage shunt with increasing gestation; nor did these values differ significantly from non-pregnant values in the same patients.", "contents": "Maternal blood-gases, PAo2--Pao2), hysiological shunt and VD/VT in normal pregnancy. Serial measurements of maternal blood-gases, alveolar-to-arterial oxygen tension difference (PAO2--PaO), calculated pulmonary venous admixture (physiological shunt), deadspace/tidal volume ratio (VD/VT), and respiratory minute volume have been made in a carefully selected group of normal pregnant patients at 12, 24, 32 and 38 weeks of gestation and 5 weeks after delivery. All measurements were made in the semi-recumbent position with a left lateral pelvic tilt. Mean arterial PO2 was consistently greater than 100 mm Hg throughout pregnancy, although the value decreased from 106.4 mm Hg at 12 weeks of gestation to 101.8 mm Hg at the 38th week. Despite this decrease there was no change in (PAO2--PaO2) VD/VT, or percentage shunt with increasing gestation; nor did these values differ significantly from non-pregnant values in the same patients."}
{"id": "PMID:10938", "title": "Metabolism of lorazepam.", "content": "The metabolism of lorazepam by man and four other species is reviewed. Lorazepam and its metabolites in blood, urine and faeces were identified by thin-layer and gas chromatography and by mass spectrometry. The principal metabolite in man, dog, pig and cat is the glucuronide, but the rat produces other metabolites after small doses of lorazepam, and significant amounts of the glucuronide only after high doses. Since all metabolites, except the glucuronide, occur in small quantities only in man, most studies in man have been confined to an estimation of gree and conjugated lorazepam. Blood concentrations of unconjugated lorazepam peak at 1-4 h, significant concentrations persisting for 24 h and decreasing slowly over the next 24 h. About 95% of a dose of lorazepam was accounted for in urine and faeces over a period of 5 days; 74.5% was excreted in the urine as lorazepam glucuronide and 13.5% as minor metabolites. The excretory half-life was 12 h. The blood concentrations and excretion rates are compatible with the clinical effects of lorazepam.", "contents": "Metabolism of lorazepam. The metabolism of lorazepam by man and four other species is reviewed. Lorazepam and its metabolites in blood, urine and faeces were identified by thin-layer and gas chromatography and by mass spectrometry. The principal metabolite in man, dog, pig and cat is the glucuronide, but the rat produces other metabolites after small doses of lorazepam, and significant amounts of the glucuronide only after high doses. Since all metabolites, except the glucuronide, occur in small quantities only in man, most studies in man have been confined to an estimation of gree and conjugated lorazepam. Blood concentrations of unconjugated lorazepam peak at 1-4 h, significant concentrations persisting for 24 h and decreasing slowly over the next 24 h. About 95% of a dose of lorazepam was accounted for in urine and faeces over a period of 5 days; 74.5% was excreted in the urine as lorazepam glucuronide and 13.5% as minor metabolites. The excretory half-life was 12 h. The blood concentrations and excretion rates are compatible with the clinical effects of lorazepam."}
{"id": "PMID:10940", "title": "Comparison of the beta2-adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline by the intravenous route in man.", "content": "1 The bronchodilating efficacy and the degree of beta2-adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline were determined in seven subjects who exhibited histamine-induced bronchoconstriction. 2 Rimiterol, 0.5 (high dose) and 0.05 (low dose) mug kg-1 min-1, salbutamol, 0.3 and 0.03 mug kg-1 min-1, isoprenaline, 0.05 and 0.005 mug kg-1 min-1 and placebo were administered by a single intravenous injection over 6 min, and the protection against histamine-induced bronchoconstriction, changes in heart rate, pulse pressure and skeletal muscle tremor were measured. 3 Rimiterol (98%), salbutamol (96%) and isoprenaline (69%) protected against histamine-induced bronchoconstriction. For these ventilatory responses, there was a heart rate increase of 31.9, 24.7 and 44.3 beats/min for rimiterol, salbutamol and isoprenaline respectively. The three drugs produced similar increases in pulse pressure and tremor. 4 Significant dose-responses were obtained for all the parameters with each drug. 5 Isoprenaline was approximately 7 and 5 times as potent as rimiterol and salbutamol respectively in bronchodilator action when equimolar doses were compared. Similarly, isoprenaline was approximately 14 and 10 times as potent in increasing the heart rate as rimiterol and salbutamol respectively. 6 Rimiterol, a new beta-adrenoceptor stimulating drug, is an effective bronchodilator and has similar beta2-adrenoceptor selectivity to salbutamol when administered intravenously. The relative potencies and degrees of beta2-adrenoceptor selectivity of these drugs depend partly on their route of administration.", "contents": "Comparison of the beta2-adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline by the intravenous route in man. 1 The bronchodilating efficacy and the degree of beta2-adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline were determined in seven subjects who exhibited histamine-induced bronchoconstriction. 2 Rimiterol, 0.5 (high dose) and 0.05 (low dose) mug kg-1 min-1, salbutamol, 0.3 and 0.03 mug kg-1 min-1, isoprenaline, 0.05 and 0.005 mug kg-1 min-1 and placebo were administered by a single intravenous injection over 6 min, and the protection against histamine-induced bronchoconstriction, changes in heart rate, pulse pressure and skeletal muscle tremor were measured. 3 Rimiterol (98%), salbutamol (96%) and isoprenaline (69%) protected against histamine-induced bronchoconstriction. For these ventilatory responses, there was a heart rate increase of 31.9, 24.7 and 44.3 beats/min for rimiterol, salbutamol and isoprenaline respectively. The three drugs produced similar increases in pulse pressure and tremor. 4 Significant dose-responses were obtained for all the parameters with each drug. 5 Isoprenaline was approximately 7 and 5 times as potent as rimiterol and salbutamol respectively in bronchodilator action when equimolar doses were compared. Similarly, isoprenaline was approximately 14 and 10 times as potent in increasing the heart rate as rimiterol and salbutamol respectively. 6 Rimiterol, a new beta-adrenoceptor stimulating drug, is an effective bronchodilator and has similar beta2-adrenoceptor selectivity to salbutamol when administered intravenously. The relative potencies and degrees of beta2-adrenoceptor selectivity of these drugs depend partly on their route of administration."}
{"id": "PMID:10941", "title": "Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.", "content": "1 The residual effects of two benzodiazepines, nitrazepam (10 mg) and flurazepam hydrochloride (30 mg), and pentobarbitone sodium (200 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after ingestion of each drug. Impaired performance on adaptive tracking was observed at 10 h, 13 h, 16 h and 19 h after nitrazepam and pentobarbitone sodium and at 10 h, 13 h and 16 h after flurazepam hydrochloride. Enhanced performance was observed at 34 h after nitrazepam and pentobarbitone sodium. 2 Increased reaction time persisted to 16 h after nitrazepam, flurazepam hydrochloride and pentobarbitone sodium and reaction time was also increased at 34 h after nitrazepam and pentobarbitone sodium. 3 During the morning immediately after ingestion, the subjects as a group were able to differentiate correctly between placebo and drugs, but they were not able to assess accurately the persistence of the residual effects of nitrazepam and pentobarbitone sodium. 4 Flurazepam hydrochloride would appear to be a more promising benzodiazepine than nitrazepam for use as a hypnotic by persons involved in skilled activity. There was a rapid recovery of performance during the afternoon and, unlike pentobarbitone sodium and nitrazepam, subjects retained the ability to recognize impaired skill.", "contents": "Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance. 1 The residual effects of two benzodiazepines, nitrazepam (10 mg) and flurazepam hydrochloride (30 mg), and pentobarbitone sodium (200 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after ingestion of each drug. Impaired performance on adaptive tracking was observed at 10 h, 13 h, 16 h and 19 h after nitrazepam and pentobarbitone sodium and at 10 h, 13 h and 16 h after flurazepam hydrochloride. Enhanced performance was observed at 34 h after nitrazepam and pentobarbitone sodium. 2 Increased reaction time persisted to 16 h after nitrazepam, flurazepam hydrochloride and pentobarbitone sodium and reaction time was also increased at 34 h after nitrazepam and pentobarbitone sodium. 3 During the morning immediately after ingestion, the subjects as a group were able to differentiate correctly between placebo and drugs, but they were not able to assess accurately the persistence of the residual effects of nitrazepam and pentobarbitone sodium. 4 Flurazepam hydrochloride would appear to be a more promising benzodiazepine than nitrazepam for use as a hypnotic by persons involved in skilled activity. There was a rapid recovery of performance during the afternoon and, unlike pentobarbitone sodium and nitrazepam, subjects retained the ability to recognize impaired skill."}
{"id": "PMID:10942", "title": "Residual effects of flunitrazepam.", "content": "1 Twelve normal subjects were tested on a large battery of tests after a hypnotic dose of flunitrazepam(1 or 2 mg) and a placebo. Psychological tests were given 12 h after the drug and physiological tests 12, 15 and 18 h after the drug. 2 The tests included self-ratings of hypnotic effects and mood, the electroencephalogram, the auditory electroencephalographic evoked response, skin conductance, tapping, card-sorting and the symbol copying test. 3 Both doses of flunitrazepam were effective hypnotics according to the ratings, with an anxiolytic effect the following day. The EEG was significantly altered up to 18 h after the drug and the behavioural tests showed a motor impairment 12 h after drug administration. 4 Nearly all changes displayed linear dose-related trends.", "contents": "Residual effects of flunitrazepam. 1 Twelve normal subjects were tested on a large battery of tests after a hypnotic dose of flunitrazepam(1 or 2 mg) and a placebo. Psychological tests were given 12 h after the drug and physiological tests 12, 15 and 18 h after the drug. 2 The tests included self-ratings of hypnotic effects and mood, the electroencephalogram, the auditory electroencephalographic evoked response, skin conductance, tapping, card-sorting and the symbol copying test. 3 Both doses of flunitrazepam were effective hypnotics according to the ratings, with an anxiolytic effect the following day. The EEG was significantly altered up to 18 h after the drug and the behavioural tests showed a motor impairment 12 h after drug administration. 4 Nearly all changes displayed linear dose-related trends."}
{"id": "PMID:10943", "title": "A clinical and psychometric evaluation of flurazepam.", "content": "1 The efficacy of flurazepam (15 mg or 30 mg) as a hypnotic, and the residual effects of each dose were compared with placebo in a double-blind cross-over trial involving thirty patients in a general practice setting. Patients received each medication for one week. Daily self-ratings of onset, duration and quality of sleep, together with reports of any untoward effects were made. At the end of each period of medication psychomotor tests (reaction time, pursuit rotor, tapping speed) were administered at 09.00 hours. 2 Both doses of flurazepam were significantly more effective than placebo in inducing sleep, improving the quality of sleep and extending its duration. 3 'Hangover' effects were marked following 30 mg, but not after flurazepam (15 mg). Flurazepam (30 mg, but not 15 mg) significantly impaired performance on the pursuit rotor test and tapping speed. Flurazepam thus appears to be an effective hypnotic drug with the optimum dose for use in general practice being 15 mg at night.", "contents": "A clinical and psychometric evaluation of flurazepam. 1 The efficacy of flurazepam (15 mg or 30 mg) as a hypnotic, and the residual effects of each dose were compared with placebo in a double-blind cross-over trial involving thirty patients in a general practice setting. Patients received each medication for one week. Daily self-ratings of onset, duration and quality of sleep, together with reports of any untoward effects were made. At the end of each period of medication psychomotor tests (reaction time, pursuit rotor, tapping speed) were administered at 09.00 hours. 2 Both doses of flurazepam were significantly more effective than placebo in inducing sleep, improving the quality of sleep and extending its duration. 3 'Hangover' effects were marked following 30 mg, but not after flurazepam (15 mg). Flurazepam (30 mg, but not 15 mg) significantly impaired performance on the pursuit rotor test and tapping speed. Flurazepam thus appears to be an effective hypnotic drug with the optimum dose for use in general practice being 15 mg at night."}
{"id": "PMID:10944", "title": "Bioavailability and dissolution of different formulations of oxytetracycline preparations.", "content": "1 The concentration of oxytetracycline in plasma was studied by microbiological assay after oral administration of five different preparations of the antibiotic. None of these preparations had been studied previously. 2 There was a statistically significant correlation between the time required for 50% dissolution at pH 2 and biological availability, as assessed by the peak plasma level or the area under the plasma concentration-time curve. 3 The mean bioavailability of oxytetracycline was greatest with preparations of the hydrochloride, and with film-coated tablets of the dihydrate. In contrast, sugar-coated tablets of oxytetracycline dihydrate were associated with poorer dissolution characteristics and reduced biological availability.", "contents": "Bioavailability and dissolution of different formulations of oxytetracycline preparations. 1 The concentration of oxytetracycline in plasma was studied by microbiological assay after oral administration of five different preparations of the antibiotic. None of these preparations had been studied previously. 2 There was a statistically significant correlation between the time required for 50% dissolution at pH 2 and biological availability, as assessed by the peak plasma level or the area under the plasma concentration-time curve. 3 The mean bioavailability of oxytetracycline was greatest with preparations of the hydrochloride, and with film-coated tablets of the dihydrate. In contrast, sugar-coated tablets of oxytetracycline dihydrate were associated with poorer dissolution characteristics and reduced biological availability."}
{"id": "PMID:10948", "title": "A review of the animal pharmacology of labetalol, a combined alpha- and beta-adrenoceptor-blocking drug.", "content": "1 The animal pharmacology of labetalol, a drug that blocks both alpha- and beta-adrenoreceptors, is reviewed. 2 In isolated tissues the blockade by labetalol of both alpha- and beta-adrenoreceptors satisfied accepted critera for competitive antagonism. In contrast phentolamine was a competitive antagonist at alpha-adrenoreceptors only, and propranolol a competitive antagonist at beta-adrenoreceptors only. Labetalol was 6-10 times less potent than phentolamine in blocking alpha-adrenoreceptors and 1.5-3 times less potent than propranolol in blocking beta-adrenoreceptors. Labetalol itself was 4-8 times more potent at beta- than at alpha-adrenoreceptors. 3 In anaesthetized dogs labetalol given intravenously blocked vasopressor responses to phenylephrine positive chronotropic, vasodepressor and bronchodilator response to isoprenaline. Phentolamine blocked the effect of phenylephrine only, and propranolol the effects of isoprenaline only. Labetalol was about 7 times less potent than phentolamine in blocking alpha-adrenoreceptors, about 4 times less potent than propranolol in blocking cardiac beta1-adrenoreceptors, and 11-17 times less potent than propranolol in blocking vascular and bronchial beta2-adrenoceptors. This difference in the relative potency of labetalol arises because propranolol is a slightly more potent antagonist at beta2- than at beta1-adrenoreceptors. Labetaol itself was about 16 times more potent at cardiac beta1- than at vascular alpha-adrenoreceptors. In conscious dogs labetaol given orally blocked vasopressor responses to phenylephrine and positive chonotropic responses to isoprenaline. 4 In anesthetized dogs and pithed rats labetaol blocked alpha- or beta-adrenoreceptor-mediated responses to sympathetic nerve stimulation and intravenously administered phenylephrine or isoprenaline to approximately the same extent. 5 Labetalol does not possess partial agonist (intrinsic sympathomimetic) activity at cardiac beta1-adrenoreceptors. 6 The blocking action of labetalol both in vivo was shown to be specific for alpha- and beta-adrenoreceptors. 7 The haemodynamic effects of labetalol are attributable to its adrenoreceptor-blocking actions. The observed responses vary from one experiment situation to another depending on the balance of autonomic influences. For example, in barbitone-anaesthetized dogs, in which sympathetic tone predominates, both labetalol and propranolol reduced heart rate, contractility, output and work--effects which are attributable to beta-adrenoreceptor blockade. Labetalol differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger falls in blood pressure at equipotent beta-adrenoreceptor-blocking doses. These differences are probably attributable to peripheral vasodilatation resulting from the vascular alpha-adrenoreceptor-blocking action of labetalol...", "contents": "A review of the animal pharmacology of labetalol, a combined alpha- and beta-adrenoceptor-blocking drug. 1 The animal pharmacology of labetalol, a drug that blocks both alpha- and beta-adrenoreceptors, is reviewed. 2 In isolated tissues the blockade by labetalol of both alpha- and beta-adrenoreceptors satisfied accepted critera for competitive antagonism. In contrast phentolamine was a competitive antagonist at alpha-adrenoreceptors only, and propranolol a competitive antagonist at beta-adrenoreceptors only. Labetalol was 6-10 times less potent than phentolamine in blocking alpha-adrenoreceptors and 1.5-3 times less potent than propranolol in blocking beta-adrenoreceptors. Labetalol itself was 4-8 times more potent at beta- than at alpha-adrenoreceptors. 3 In anaesthetized dogs labetalol given intravenously blocked vasopressor responses to phenylephrine positive chronotropic, vasodepressor and bronchodilator response to isoprenaline. Phentolamine blocked the effect of phenylephrine only, and propranolol the effects of isoprenaline only. Labetalol was about 7 times less potent than phentolamine in blocking alpha-adrenoreceptors, about 4 times less potent than propranolol in blocking cardiac beta1-adrenoreceptors, and 11-17 times less potent than propranolol in blocking vascular and bronchial beta2-adrenoceptors. This difference in the relative potency of labetalol arises because propranolol is a slightly more potent antagonist at beta2- than at beta1-adrenoreceptors. Labetaol itself was about 16 times more potent at cardiac beta1- than at vascular alpha-adrenoreceptors. In conscious dogs labetaol given orally blocked vasopressor responses to phenylephrine and positive chonotropic responses to isoprenaline. 4 In anesthetized dogs and pithed rats labetaol blocked alpha- or beta-adrenoreceptor-mediated responses to sympathetic nerve stimulation and intravenously administered phenylephrine or isoprenaline to approximately the same extent. 5 Labetalol does not possess partial agonist (intrinsic sympathomimetic) activity at cardiac beta1-adrenoreceptors. 6 The blocking action of labetalol both in vivo was shown to be specific for alpha- and beta-adrenoreceptors. 7 The haemodynamic effects of labetalol are attributable to its adrenoreceptor-blocking actions. The observed responses vary from one experiment situation to another depending on the balance of autonomic influences. For example, in barbitone-anaesthetized dogs, in which sympathetic tone predominates, both labetalol and propranolol reduced heart rate, contractility, output and work--effects which are attributable to beta-adrenoreceptor blockade. Labetalol differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger falls in blood pressure at equipotent beta-adrenoreceptor-blocking doses. These differences are probably attributable to peripheral vasodilatation resulting from the vascular alpha-adrenoreceptor-blocking action of labetalol..."}
{"id": "PMID:10949", "title": "Pharmacological effects of labetalol in man.", "content": "1 The pharmacological effects of labetalol have been studied in normal healthy subjects. The results of these studies are reviewed. 2 In the evaluation of the beta-adrenoreceptor-blocking effects of labetalol various indices of beta-adrenoceptor blockade in man were used. Labetalol administered orally and intravenously competitively antagonized the effects of isoprenaline on heart rate and diastolic blood pressure. The beta-adrenoceptor blockade induced was regarded as 'non-selective'. In addition, labetalol produced dose-related inhibitory effects on exercise-induced increases in heart rate any systolic blood pressure and similar dose-related inhibitory effects on the tachycardia induced by valsalva's manoeuvre. Labetalol had only a modest inhibitory effect on the tachycardia induced by tilting since blood pressure was reduced on a dose-related basis. 3 Labetalol was a specific competitive antagonist of the alpha-adrenoceptor agonist effects of systemically administered phenylephrine and locally infused noradrenaline. In addition, oral and intravenous administration of labetalol reduced systolic and diastolic blood pressure in the supine, standing and sitting positions. 4 The onset and duration of the alpha- and beta-antagonist effects of oral labetalol did not seem to be dissociated in time and there was a close correlation between the change in plasma concentration and pharmacological effects. 5 In comparative studies with propranolol, similar beta-antagonist effects were observed but propranolol was 4-6 times more potent weight for weight. Precise comparison, however, was complicated by the combined alpha- and beta -effects of labetalol, especially as the predominant effect of labetalol in normotensive subjects was to reduce blood pressure; whereas the predominant effect of propranolol was to reduce heart rate. In addition propranolol had inhibitory effects on ventilatory function in normal subjects, whereas labetalol in equivalent beta-adrenoreceptor-blocking doses did not. 6 From the details of the studies reviewed it was concluded that in man labetalol possesses combined alpha- and beta-adrenoreceptor antagonist properties.", "contents": "Pharmacological effects of labetalol in man. 1 The pharmacological effects of labetalol have been studied in normal healthy subjects. The results of these studies are reviewed. 2 In the evaluation of the beta-adrenoreceptor-blocking effects of labetalol various indices of beta-adrenoceptor blockade in man were used. Labetalol administered orally and intravenously competitively antagonized the effects of isoprenaline on heart rate and diastolic blood pressure. The beta-adrenoceptor blockade induced was regarded as 'non-selective'. In addition, labetalol produced dose-related inhibitory effects on exercise-induced increases in heart rate any systolic blood pressure and similar dose-related inhibitory effects on the tachycardia induced by valsalva's manoeuvre. Labetalol had only a modest inhibitory effect on the tachycardia induced by tilting since blood pressure was reduced on a dose-related basis. 3 Labetalol was a specific competitive antagonist of the alpha-adrenoceptor agonist effects of systemically administered phenylephrine and locally infused noradrenaline. In addition, oral and intravenous administration of labetalol reduced systolic and diastolic blood pressure in the supine, standing and sitting positions. 4 The onset and duration of the alpha- and beta-antagonist effects of oral labetalol did not seem to be dissociated in time and there was a close correlation between the change in plasma concentration and pharmacological effects. 5 In comparative studies with propranolol, similar beta-antagonist effects were observed but propranolol was 4-6 times more potent weight for weight. Precise comparison, however, was complicated by the combined alpha- and beta -effects of labetalol, especially as the predominant effect of labetalol in normotensive subjects was to reduce blood pressure; whereas the predominant effect of propranolol was to reduce heart rate. In addition propranolol had inhibitory effects on ventilatory function in normal subjects, whereas labetalol in equivalent beta-adrenoreceptor-blocking doses did not. 6 From the details of the studies reviewed it was concluded that in man labetalol possesses combined alpha- and beta-adrenoreceptor antagonist properties."}
{"id": "PMID:10950", "title": "Haemodynamic effects of combined alpha- and beta-adrenoreceptor blockade after intravenous labetalol in hypertensive patients at rest and during exercise.", "content": "1 The haemodynamic effects of labetalol 50 mg intravenously were studied in 13 hypertensive patients at rest in the supine and upright positions and during exercise using percutaneous right heart and brachial artery catheterization. 2 Labetalol induced immediate significant reductions in systolic and diastolic blood pressures in all conditions. 3 Heart rate, stroke volume and cardiac output were not significantly altered in the supine position at rest but were significantly reduced in the upright position. In addition systemic vascular resistance was significantly reduced. 4 During exercise, heart-rate, cardiac output and vascular resistance were significantly reduced; stroke volume was increased. Left ventriclac filling pressures were unchanged both at rest and during exercise. 5 It was concluded that these changes resulted from blockade to both alpha- and beta-adrenoreceptor.", "contents": "Haemodynamic effects of combined alpha- and beta-adrenoreceptor blockade after intravenous labetalol in hypertensive patients at rest and during exercise. 1 The haemodynamic effects of labetalol 50 mg intravenously were studied in 13 hypertensive patients at rest in the supine and upright positions and during exercise using percutaneous right heart and brachial artery catheterization. 2 Labetalol induced immediate significant reductions in systolic and diastolic blood pressures in all conditions. 3 Heart rate, stroke volume and cardiac output were not significantly altered in the supine position at rest but were significantly reduced in the upright position. In addition systemic vascular resistance was significantly reduced. 4 During exercise, heart-rate, cardiac output and vascular resistance were significantly reduced; stroke volume was increased. Left ventriclac filling pressures were unchanged both at rest and during exercise. 5 It was concluded that these changes resulted from blockade to both alpha- and beta-adrenoreceptor."}
{"id": "PMID:10951", "title": "Combined alpha- and beta-adrenoreceptors blockade with oral labetalol in hypertensive patients with reference to haemodynamic effects at rest and during exercise.", "content": "Twelve hypertensive patients received oral labetalol treatment (average final dose 1,200 mg/d) over a period of 16 months. 2 Satisfactory blood pressure control was maintained both at rest and after exercise. 3 Plasma renin activity was significantly reduced. 4 Postural hypotension measured in this group of patients after a single dose of labetalol 50 mg intravenously was considerably reduced during long-term oral treatment. 5 No serious side-effects were observed nor were there any significant changes in haematological and biochemical variables during the period. 6 Haemodynamic data obtained in two of the patients after 16 months' treatment suggests that the haemodynamic profile observed after acute intravenous administration is maintained after prolonged oral treatment.", "contents": "Combined alpha- and beta-adrenoreceptors blockade with oral labetalol in hypertensive patients with reference to haemodynamic effects at rest and during exercise. Twelve hypertensive patients received oral labetalol treatment (average final dose 1,200 mg/d) over a period of 16 months. 2 Satisfactory blood pressure control was maintained both at rest and after exercise. 3 Plasma renin activity was significantly reduced. 4 Postural hypotension measured in this group of patients after a single dose of labetalol 50 mg intravenously was considerably reduced during long-term oral treatment. 5 No serious side-effects were observed nor were there any significant changes in haematological and biochemical variables during the period. 6 Haemodynamic data obtained in two of the patients after 16 months' treatment suggests that the haemodynamic profile observed after acute intravenous administration is maintained after prolonged oral treatment."}
{"id": "PMID:10952", "title": "Labetalol, a new alpha- and beta-adrenoreceptor blocking agent, in hypertension.", "content": "1Labetalol is a new compound with antagonistic effects at both alpha- and beta-adrenoreceptor sites. 2 When given to 12 hypertensive patients at an average daily dosage of 273 mg for 7 months statistically significant reductions (compared with pretreatment values) in recumbent and standing blood pressure were observed. 3 Treatment has to be withdrawn in one patient because of vivid dreams, and dosage was reduced in one patient because of dizziness. Otherwise no side-effects of importance were noted. 4 It can therefore be concluded that labetalol offers a useful anti-hypertensive effect and that this compound is well tolerated.", "contents": "Labetalol, a new alpha- and beta-adrenoreceptor blocking agent, in hypertension. 1Labetalol is a new compound with antagonistic effects at both alpha- and beta-adrenoreceptor sites. 2 When given to 12 hypertensive patients at an average daily dosage of 273 mg for 7 months statistically significant reductions (compared with pretreatment values) in recumbent and standing blood pressure were observed. 3 Treatment has to be withdrawn in one patient because of vivid dreams, and dosage was reduced in one patient because of dizziness. Otherwise no side-effects of importance were noted. 4 It can therefore be concluded that labetalol offers a useful anti-hypertensive effect and that this compound is well tolerated."}
{"id": "PMID:10953", "title": "Intravenous labetalol in hypertensive patients treated with beta-adrenoreceptor-blocking drugs.", "content": "1 The effect of intravenous injections of labetalol at doses of 1 and 2 mg/kg was studied in 15 patients with severe hypertension inadequately controlled by beta-adrenoreceptor-blocking drugs. 2 At a dose of 1 mg/kg there was a slight but statistically insignificant reduction in blood pressure. When 2 mg/kg was given there was a prolonged (6 h) significant reduction in lying blood pressure. At both dose levels there was a small initial increase in pulse rate but forced peak flow was not affected. 3 Side-effects were limited to transient postural hypotension and a feeling of warmth. 4 It is concluded that intravenous labetalol at a dose of 2 mg/kg is safe and effective in rapidly reducing blood pressure in patients already receiving beta-adrenoreceptor-blocking drugs.", "contents": "Intravenous labetalol in hypertensive patients treated with beta-adrenoreceptor-blocking drugs. 1 The effect of intravenous injections of labetalol at doses of 1 and 2 mg/kg was studied in 15 patients with severe hypertension inadequately controlled by beta-adrenoreceptor-blocking drugs. 2 At a dose of 1 mg/kg there was a slight but statistically insignificant reduction in blood pressure. When 2 mg/kg was given there was a prolonged (6 h) significant reduction in lying blood pressure. At both dose levels there was a small initial increase in pulse rate but forced peak flow was not affected. 3 Side-effects were limited to transient postural hypotension and a feeling of warmth. 4 It is concluded that intravenous labetalol at a dose of 2 mg/kg is safe and effective in rapidly reducing blood pressure in patients already receiving beta-adrenoreceptor-blocking drugs."}
{"id": "PMID:10955", "title": "Arterialized ear lobe blood samples for blood gas tensions.", "content": "The accuracy of arterialized blood samples both at rest and during exercise is described in comparison to simultaneous arterial blood samples. The technique was found to be reliable and sufficiently accurate for clinical exercise testing, with no significant differences for Po2 or Pco2 between the two methods.", "contents": "Arterialized ear lobe blood samples for blood gas tensions. The accuracy of arterialized blood samples both at rest and during exercise is described in comparison to simultaneous arterial blood samples. The technique was found to be reliable and sufficiently accurate for clinical exercise testing, with no significant differences for Po2 or Pco2 between the two methods."}
{"id": "PMID:10956", "title": "Preparation and storage of platelet concentrates. II. Storage variables influencing platelet viability and function.", "content": "Factors affecting the viability and function of stored platelet concentrates have been investigated in a blood component programme. It was found that platelets could be maintained for up to 72 h without bacterial contamination under the following conditions: (1) surgical skin preparation at venipuncture site; (2) blood collection in CPD or ACD anticoagulant in a closed bag system; (3) centrifugation of PRP at 3000 g for 20 min; (4) storage in Fenwal PL-146, Cutter CL-2383, or McGaw plastic bags; (5) resuspension of the platelet pellet in 70 ml residual plasma; (6) storage at 22+/-2 degrees C; and (7) constant gentle mixing throughout storage. Platelet viability as determined by recovery and survival is largely maintained, as is platelet function measured by template bleeding time. Both viability and function of concentrated platelets stored at 4 degrees C are severely compromised.", "contents": "Preparation and storage of platelet concentrates. II. Storage variables influencing platelet viability and function. Factors affecting the viability and function of stored platelet concentrates have been investigated in a blood component programme. It was found that platelets could be maintained for up to 72 h without bacterial contamination under the following conditions: (1) surgical skin preparation at venipuncture site; (2) blood collection in CPD or ACD anticoagulant in a closed bag system; (3) centrifugation of PRP at 3000 g for 20 min; (4) storage in Fenwal PL-146, Cutter CL-2383, or McGaw plastic bags; (5) resuspension of the platelet pellet in 70 ml residual plasma; (6) storage at 22+/-2 degrees C; and (7) constant gentle mixing throughout storage. Platelet viability as determined by recovery and survival is largely maintained, as is platelet function measured by template bleeding time. Both viability and function of concentrated platelets stored at 4 degrees C are severely compromised."}
{"id": "PMID:10957", "title": "Solubilization, partial purification and radioassay for the intrinsic factor receptor from the ileal mucosa.", "content": "A macromolecule which binds intrinsic factor saturated with vitamin B12 has been solubilized from the guinea-pig ileum by homogenization followed by mechanical disruption without organic solvents or detergents. This intrinsic factor 'receptor' was further purified by precipitation with 30% saturated ammonium sulphate, centrifugation at 105000 g, and filtration through Sephadex G-200. Failure to precipitate the receptor following centrifugation at 105000 g for 3 h and filtration of the receptor with the included volumes through Sepharose 4B and 6B was evidence that it was solubilized. The purification of the receptor was monitored by a radiometric assay where the intrinsic factor-[57Co]vitamin-B12 complex coupled to the solubilized receptor precipitated at 15% sodium sulphate while intrinsic factor-[57Co]B12 alone remained soluble at this salt concentration. This radioassay also permitted the in vitro study of the interaction of the solubilized receptor and intrinsic factor saturated with [57Co]B12. The receptor did not bind intrinsic factor-[57Co]B12 below pH 5 while binding was observed to pH 9.0. Binding was equivalent at 37 degrees C and 25 degrees C, but was markedly reduced at 4 degrees C and 56 degrees C and was destroyed at 100 degrees C. The receptor resisted 60 min of digestion by trypsin, chymotrypsin, pronase and subtilisin. After 180 min digestion, pronase and subtilisin inactivated 90% and 41% of the receptor respectively, whereas trypsin and chymotrypsin inactivated only 21% and 23%. Trisodium EDTA inhibited the binding of intrinsic factor-[57Co]B12 to the receptor and this inhibition could be reversed by the addition of excess Ca2+. Mg2+ and Mn2+ were less effective than Ca2+ for the activity of the receptor. Kinetic analysis of the reaction indicated a maximum velocity of 0.083 nmole IF bound B12/min with a Km of 1.36 x 10(-10) M. The solubilized receptor had a greater affinity for intrinsic factor bound to vitamin B12 than for intrinsic factor free of vitamin B12. The solubilization of this intrinsic factor receptor without chemicals suggests that it is not an integral component of the microvillus membranes hydrophobically bonded to the lipid matrix, but rather a peripheral protein weakly associated with the membrane by non-covalent interaction.", "contents": "Solubilization, partial purification and radioassay for the intrinsic factor receptor from the ileal mucosa. A macromolecule which binds intrinsic factor saturated with vitamin B12 has been solubilized from the guinea-pig ileum by homogenization followed by mechanical disruption without organic solvents or detergents. This intrinsic factor 'receptor' was further purified by precipitation with 30% saturated ammonium sulphate, centrifugation at 105000 g, and filtration through Sephadex G-200. Failure to precipitate the receptor following centrifugation at 105000 g for 3 h and filtration of the receptor with the included volumes through Sepharose 4B and 6B was evidence that it was solubilized. The purification of the receptor was monitored by a radiometric assay where the intrinsic factor-[57Co]vitamin-B12 complex coupled to the solubilized receptor precipitated at 15% sodium sulphate while intrinsic factor-[57Co]B12 alone remained soluble at this salt concentration. This radioassay also permitted the in vitro study of the interaction of the solubilized receptor and intrinsic factor saturated with [57Co]B12. The receptor did not bind intrinsic factor-[57Co]B12 below pH 5 while binding was observed to pH 9.0. Binding was equivalent at 37 degrees C and 25 degrees C, but was markedly reduced at 4 degrees C and 56 degrees C and was destroyed at 100 degrees C. The receptor resisted 60 min of digestion by trypsin, chymotrypsin, pronase and subtilisin. After 180 min digestion, pronase and subtilisin inactivated 90% and 41% of the receptor respectively, whereas trypsin and chymotrypsin inactivated only 21% and 23%. Trisodium EDTA inhibited the binding of intrinsic factor-[57Co]B12 to the receptor and this inhibition could be reversed by the addition of excess Ca2+. Mg2+ and Mn2+ were less effective than Ca2+ for the activity of the receptor. Kinetic analysis of the reaction indicated a maximum velocity of 0.083 nmole IF bound B12/min with a Km of 1.36 x 10(-10) M. The solubilized receptor had a greater affinity for intrinsic factor bound to vitamin B12 than for intrinsic factor free of vitamin B12. The solubilization of this intrinsic factor receptor without chemicals suggests that it is not an integral component of the microvillus membranes hydrophobically bonded to the lipid matrix, but rather a peripheral protein weakly associated with the membrane by non-covalent interaction."}
{"id": "PMID:10958", "title": "Effect of pyridoxal 5'-phosphate on the oxygen affinity of human erythrocytes.", "content": "Pyridoxal 5'-phosphate (PLP), an allosteric effector for the oxygenation of haemoglobin, was incorporated readily into erythrocytes and disappeared from them by simple passive diffusion. The disappearance of PLP from the cells was accelerated by the generation of 2,3-DPG in a medium of inosine, pyruvate and phosphate. The oxygen dissociation curve measured at an extracellular pH of 7.4 demonstrated that PLP incorporated into the cells also lowered the oxygen affinity and that PLP functionally compensated for a metabolically reduced 2,3-DPG. However, the dependency of the oxygen affinity on the intracellular PLP concentration showed a different pattern from the observed for 2,3-DPG. On the other hand, the lowering of intracellular pH by organic phosphates accumulated in the cells was much larger with PLP than with 2,3-DPG. The peculiar relationship between the oxygen affinity of erythrocytes and the intracellular PLP concentration is discussed in detail. The present study may offer a new prospect for the preservation of blood with a normal function.", "contents": "Effect of pyridoxal 5'-phosphate on the oxygen affinity of human erythrocytes. Pyridoxal 5'-phosphate (PLP), an allosteric effector for the oxygenation of haemoglobin, was incorporated readily into erythrocytes and disappeared from them by simple passive diffusion. The disappearance of PLP from the cells was accelerated by the generation of 2,3-DPG in a medium of inosine, pyruvate and phosphate. The oxygen dissociation curve measured at an extracellular pH of 7.4 demonstrated that PLP incorporated into the cells also lowered the oxygen affinity and that PLP functionally compensated for a metabolically reduced 2,3-DPG. However, the dependency of the oxygen affinity on the intracellular PLP concentration showed a different pattern from the observed for 2,3-DPG. On the other hand, the lowering of intracellular pH by organic phosphates accumulated in the cells was much larger with PLP than with 2,3-DPG. The peculiar relationship between the oxygen affinity of erythrocytes and the intracellular PLP concentration is discussed in detail. The present study may offer a new prospect for the preservation of blood with a normal function."}
{"id": "PMID:10961", "title": "Phosphorus-31 Fourier transform nuclear magnetic resonance study of mononucleotides and dinucleotides. 1. Chemical shifts.", "content": "A phosphorus-31 nuclear magnetic resonance (NMR) study of adenine, uracil, and thymine mononucleotides, their cyclic analogues, and the corresponding dinucleotides is reported. From the pH dependence of phosphate chemical shifts, pKa values of 6.25-6.30 are found for all 5'-mononucleotides secondary phosphate ionization, independently from the nature of the base and the presence of a hydroxyl group at the 2' position. Conversely, substitution of a hydrogen atom for a 2'-OH lowers the pKa of 3'-monoribonucleotides from 6.25 down to 5.71-5.85. This indication of a strong influence of the 2'-hydroxyl group on the 3'-phosphate is confirmed by the existence of a 0.4 to 0.5 ppm downfield shift induced by the 2'-OH on the phosphate resonance of 3'-monoribonucleotides, and 3',5'-cyclic nucleotides and dinucleotides with respect to the deoxyribosyl analogues. Phosphate chemical shifts and titration curves are affected by the ionization and the type of the base. Typically, deviations from the theoretical Henderson-Hasselbalch plots are observed upon base titration. In addition, purine displays a more deshielding influence than pyrimidine on the phosphate groups of most of the mononucleotides (0.10 to 0.25 ppm downfield shift) with a reverse situation for dinucleotides. These effects together with the importance of stereochemical arrangement (furanose ring pucker, furanose-phosphate backbone conformation, O-P-O bond angle) on the phosphate chemical shifts are discussed.", "contents": "Phosphorus-31 Fourier transform nuclear magnetic resonance study of mononucleotides and dinucleotides. 1. Chemical shifts. A phosphorus-31 nuclear magnetic resonance (NMR) study of adenine, uracil, and thymine mononucleotides, their cyclic analogues, and the corresponding dinucleotides is reported. From the pH dependence of phosphate chemical shifts, pKa values of 6.25-6.30 are found for all 5'-mononucleotides secondary phosphate ionization, independently from the nature of the base and the presence of a hydroxyl group at the 2' position. Conversely, substitution of a hydrogen atom for a 2'-OH lowers the pKa of 3'-monoribonucleotides from 6.25 down to 5.71-5.85. This indication of a strong influence of the 2'-hydroxyl group on the 3'-phosphate is confirmed by the existence of a 0.4 to 0.5 ppm downfield shift induced by the 2'-OH on the phosphate resonance of 3'-monoribonucleotides, and 3',5'-cyclic nucleotides and dinucleotides with respect to the deoxyribosyl analogues. Phosphate chemical shifts and titration curves are affected by the ionization and the type of the base. Typically, deviations from the theoretical Henderson-Hasselbalch plots are observed upon base titration. In addition, purine displays a more deshielding influence than pyrimidine on the phosphate groups of most of the mononucleotides (0.10 to 0.25 ppm downfield shift) with a reverse situation for dinucleotides. These effects together with the importance of stereochemical arrangement (furanose ring pucker, furanose-phosphate backbone conformation, O-P-O bond angle) on the phosphate chemical shifts are discussed."}
{"id": "PMID:10962", "title": "Reaction of yeast carboxypeptidase C1 with group-specific reagents.", "content": "The reactions between yeast carboxypeptidase C and the group-specific reagents, phenylglyoxal and iodoacetamide, have been studied in detail and the reactions of residue at the active site with N-tosyl-L-phenylalanine chloromethyl ketone and diisopropyl phosphorofluoridate have been confirmed. Modification of the enzyme by either phenylglyoxal or iodoacetamide results in the loss of peptidase activity, while esterase activity remains unchanged. Inactivation by phenylglyoxal appears to be the result of the modification of a single arginine residue, whereas inhibition by iodoacetamide can be correlated with the modification of a single methionine residue. Inactivation of the enzyme by either N-tosyl-L-phenylalanine chloromethyl ketone or diisopropyl phosphorofluoridate is the result of the modification of a single histidine and a single serine residue, respectively. The pattern of inhibition indicates certain analogies in the mechanism of yeast carboxypeptidase C to pancreatic chymotrypsin, on the one hand, and to carboxypeptidase A, on the other.", "contents": "Reaction of yeast carboxypeptidase C1 with group-specific reagents. The reactions between yeast carboxypeptidase C and the group-specific reagents, phenylglyoxal and iodoacetamide, have been studied in detail and the reactions of residue at the active site with N-tosyl-L-phenylalanine chloromethyl ketone and diisopropyl phosphorofluoridate have been confirmed. Modification of the enzyme by either phenylglyoxal or iodoacetamide results in the loss of peptidase activity, while esterase activity remains unchanged. Inactivation by phenylglyoxal appears to be the result of the modification of a single arginine residue, whereas inhibition by iodoacetamide can be correlated with the modification of a single methionine residue. Inactivation of the enzyme by either N-tosyl-L-phenylalanine chloromethyl ketone or diisopropyl phosphorofluoridate is the result of the modification of a single histidine and a single serine residue, respectively. The pattern of inhibition indicates certain analogies in the mechanism of yeast carboxypeptidase C to pancreatic chymotrypsin, on the one hand, and to carboxypeptidase A, on the other."}
{"id": "PMID:10963", "title": "Identification and properties of the covalently bound flavin of beta-cyclopiazonate oxidocyclase.", "content": "Beta-Cyclopiazonate oxidocyclase from Penicillium cyclopium has been previously shown to contain flavin dinucleotide in covalent linkage to the protein. In the present study, a pure flavin mononucleotide peptide was isolated from the enzyme by tryptic-chymotryptic digestion, chromatography on Florisil and on diethylaminoethylcellulose, and hydrolysis with nucleotide pyrophosphatase. The flavin peptide contains 9 amino acids, including histidine in linkage to the flavin, and Asx as the N-terminal residue. The fluorescence of the flavin in the FMN peptide is profoundly quenched even at pH 3.2, where protonation of the imidazole prevents queching of the flavin fluorescence by histidine. This quenching appears to be due to interaction of the flavin with a tryptophan residue, as the quenching is abolished by oxidation of the tryptophan with performic acid. Similarly, the fluorescence of the tryptophan in the peptide is quenched, presumably by the flavin. The flavin of beta-cyclopiazonate oxidocylcase is attached, by the way of the 8alpha-methylene group, to the imidazole ring of a histidine. The aminoacylflavin isolated from the enzyme is identical in the pKa of its imidazole group, in reduction by NaBH4, and in other properties with synthetic 8alpha-(N1-histidyl)riboflavin. The pKa of the histidylriboflavin component of the oxidocyclase is 5.2 before and 5.0 after acid modification of the ribityl chain, as is found in the synthetic derivative. It is concluded that the enzyme contains the N1 isomer of histidylriboflavin and that acid hydrolysis of flavin peptides isolated from the oxidocyclase, while liberating histidylriboflavin, also causes acid modification of the ribityl chain of the flavin moiety.", "contents": "Identification and properties of the covalently bound flavin of beta-cyclopiazonate oxidocyclase. Beta-Cyclopiazonate oxidocyclase from Penicillium cyclopium has been previously shown to contain flavin dinucleotide in covalent linkage to the protein. In the present study, a pure flavin mononucleotide peptide was isolated from the enzyme by tryptic-chymotryptic digestion, chromatography on Florisil and on diethylaminoethylcellulose, and hydrolysis with nucleotide pyrophosphatase. The flavin peptide contains 9 amino acids, including histidine in linkage to the flavin, and Asx as the N-terminal residue. The fluorescence of the flavin in the FMN peptide is profoundly quenched even at pH 3.2, where protonation of the imidazole prevents queching of the flavin fluorescence by histidine. This quenching appears to be due to interaction of the flavin with a tryptophan residue, as the quenching is abolished by oxidation of the tryptophan with performic acid. Similarly, the fluorescence of the tryptophan in the peptide is quenched, presumably by the flavin. The flavin of beta-cyclopiazonate oxidocylcase is attached, by the way of the 8alpha-methylene group, to the imidazole ring of a histidine. The aminoacylflavin isolated from the enzyme is identical in the pKa of its imidazole group, in reduction by NaBH4, and in other properties with synthetic 8alpha-(N1-histidyl)riboflavin. The pKa of the histidylriboflavin component of the oxidocyclase is 5.2 before and 5.0 after acid modification of the ribityl chain, as is found in the synthetic derivative. It is concluded that the enzyme contains the N1 isomer of histidylriboflavin and that acid hydrolysis of flavin peptides isolated from the oxidocyclase, while liberating histidylriboflavin, also causes acid modification of the ribityl chain of the flavin moiety."}
{"id": "PMID:10964", "title": "Potentiometric determination of ionizations at the active site of papain.", "content": "The ionization behavior of groups at the active site of papain was determined from the pH dependence of the difference of proton content of papain and the methylthio derivative of the thiol group at the active site of papain (papain-S-SCH3). This difference in proton content was determined directly by two independent methods. One method involved potentiometric measurements of the protons released and demethylthiolation of papain-S-SCH3 with dithiothreitol, as a function of pH. The other method involved analogous measurements of the protons released on methylthiolation of papain with methyl methanethiosulfonate. The methylthio pH-difference titrations generated by these measurements indicate that ionization of the thiol group at the active site of papain is linked to the ionization of His-159. The pK of the thiol group changes from 3.3 to 7.6 on deprotonation of His-159 at 29 degrees C/20.05. Similarly, the pK of His-159 shifts from 4.3 to 8.5 when the active site thiol group is deprotonated. The microscopic ionization constants determined in this work for Cys-25 and His-159 indicate that equilibrium constant for transfer of the proton from Cys-25 to His-159 is 8--12, and that in the physiological pH range the active site thiol group exists mainly as a thiol anion.", "contents": "Potentiometric determination of ionizations at the active site of papain. The ionization behavior of groups at the active site of papain was determined from the pH dependence of the difference of proton content of papain and the methylthio derivative of the thiol group at the active site of papain (papain-S-SCH3). This difference in proton content was determined directly by two independent methods. One method involved potentiometric measurements of the protons released and demethylthiolation of papain-S-SCH3 with dithiothreitol, as a function of pH. The other method involved analogous measurements of the protons released on methylthiolation of papain with methyl methanethiosulfonate. The methylthio pH-difference titrations generated by these measurements indicate that ionization of the thiol group at the active site of papain is linked to the ionization of His-159. The pK of the thiol group changes from 3.3 to 7.6 on deprotonation of His-159 at 29 degrees C/20.05. Similarly, the pK of His-159 shifts from 4.3 to 8.5 when the active site thiol group is deprotonated. The microscopic ionization constants determined in this work for Cys-25 and His-159 indicate that equilibrium constant for transfer of the proton from Cys-25 to His-159 is 8--12, and that in the physiological pH range the active site thiol group exists mainly as a thiol anion."}
{"id": "PMID:10965", "title": "Studies on the noncooperative binding of the Escherichia coli DNA unwinding protein to single-stranded nucleic acids.", "content": "The noncooperative binding of the Escherichia coli DNA unwinding protein to single-stranded DNA oligomers has been studied by means of equilibrium dialysis. Dialyses were performed under a number of solution and temperature conditions using oligomers of varying length and base compositions. The results of these studies, which include a Scatchard analysis of the binding, have allowed us to propose a model for the cooperative binding of the protein to single-stranded DNA. The results of experiments dealing with the interaction of the protein with single-stranded RNA are also presented.", "contents": "Studies on the noncooperative binding of the Escherichia coli DNA unwinding protein to single-stranded nucleic acids. The noncooperative binding of the Escherichia coli DNA unwinding protein to single-stranded DNA oligomers has been studied by means of equilibrium dialysis. Dialyses were performed under a number of solution and temperature conditions using oligomers of varying length and base compositions. The results of these studies, which include a Scatchard analysis of the binding, have allowed us to propose a model for the cooperative binding of the protein to single-stranded DNA. The results of experiments dealing with the interaction of the protein with single-stranded RNA are also presented."}
{"id": "PMID:10966", "title": "A simple, quantitative approach to the coupling of photophosphorylation to electron flow in terms of proton fluxes.", "content": "A simple relationship between observed phosphorylation efficiencies (P/e ratios) and internal proton concentration in spinach chloroplast thylakoids has been derived. P/e ratios, varked by either changing the light intensity or by adding the energy transfer inhibitor, 4'-deoxyphlorizin, were found to change with internal proton concentration in accordance with this relationship. A quantitative prediction of the effect of uncouplers on the P/e ratio can probably also be made. By extrapolation of plots of observed P/e ratios against internal proton concentration divided by the overall rate of electron flow, a maximum intrinsic P/e of about 0.66 is obtained. Assuming that two protons appear inside thylakoids per electron transferred, a P/e ratio of 0.66 suggests that three internal protons are consumed for each ATP formed. Internal protons may be considered to be substrates for the phosphorylation reaction. Hill plots of phosphorylation rate vs. internal proton concentration also indicate that three protons are consumed for each ATP synthesized. Thus, the H+ concentration gradient behaves quantitatively, as well as qualitatively, as if it is the connecting link between electron flow and phosphorylation in illuminated thylakoids.", "contents": "A simple, quantitative approach to the coupling of photophosphorylation to electron flow in terms of proton fluxes. A simple relationship between observed phosphorylation efficiencies (P/e ratios) and internal proton concentration in spinach chloroplast thylakoids has been derived. P/e ratios, varked by either changing the light intensity or by adding the energy transfer inhibitor, 4'-deoxyphlorizin, were found to change with internal proton concentration in accordance with this relationship. A quantitative prediction of the effect of uncouplers on the P/e ratio can probably also be made. By extrapolation of plots of observed P/e ratios against internal proton concentration divided by the overall rate of electron flow, a maximum intrinsic P/e of about 0.66 is obtained. Assuming that two protons appear inside thylakoids per electron transferred, a P/e ratio of 0.66 suggests that three internal protons are consumed for each ATP formed. Internal protons may be considered to be substrates for the phosphorylation reaction. Hill plots of phosphorylation rate vs. internal proton concentration also indicate that three protons are consumed for each ATP synthesized. Thus, the H+ concentration gradient behaves quantitatively, as well as qualitatively, as if it is the connecting link between electron flow and phosphorylation in illuminated thylakoids."}
{"id": "PMID:10967", "title": "Properties and subcellular distribution of guanylate cyclase activity in rat renal medulla: correlation with tissue content of guanosine 3',5'-monophosphate.", "content": "The properties of the guanylate cyclase systems of outer and inner medulla of rat kidney were examined and compared with those of the renal cortex. A gradation in steady-state cyclic guanosine 3',5'-monophosphate (cGMP) levels was observed in incubated slices of these tissues (inner medula greater than outer medulla greater than cortex). This correlated with the proportion of total guanyl cyclase activity in the 100 000 g particulate fraction of each tissue, but was discordant with the relative activities of guanylate cyclase (highest in cortex) and of cGMP-phosphodiesterase (lowest in cortex) in whole tissue homogenates. Soluble guanylate cyclase of cortex and inner medulla exhibited typical Michaelis-Menten kinetics with an apparent Km for MnGTP of 0.11 mM, while the particulate enzyme from inner medulla exhibited apparent positive cooperative behavior and a decreased dependence on Mn2+. Thus, the particulate enzyme could play a key role in regulating cGMP levels inthe intact cell where Mn2+ concentrations are low. The soluble and particulate enzymes from inner medulla were further distinguished by their responses to several test agents. The soluble enzyme was activated by Ca2+, NaN3, NaNo2 and phenylhydrazine, whereas particulate activity was inhibited by Ca2+ and was unresponsive to the latter agents. In the presence of NaNo2, Mn2+ requirement of the soluble enzyme was reduced and equivalent to that of the particulate preparation. Moreover, relative responsiveness of the sollble enzyme to NaNO2 was potentiated when Mg2+ replaced Mn2+ as the sole divalent cation. These changes in metal requirements may be involved in the action of NaNO2 to increase cGMP in intact kidney. Soluble guanylate cyclase of cortex was clearly more responsive to stimulation by NaN3, Nano2, and phenylhydrazine that was soluble activity from either medullary tissue. The effectiveness of the agonists on soluble activity from outer and inner medulla cound also be distinguished. Accordingly, regulation and properties of soluble guanylate cyclase, as well as subcellular enzyme distribution, and distinct in the three regions of the kidney.", "contents": "Properties and subcellular distribution of guanylate cyclase activity in rat renal medulla: correlation with tissue content of guanosine 3',5'-monophosphate. The properties of the guanylate cyclase systems of outer and inner medulla of rat kidney were examined and compared with those of the renal cortex. A gradation in steady-state cyclic guanosine 3',5'-monophosphate (cGMP) levels was observed in incubated slices of these tissues (inner medula greater than outer medulla greater than cortex). This correlated with the proportion of total guanyl cyclase activity in the 100 000 g particulate fraction of each tissue, but was discordant with the relative activities of guanylate cyclase (highest in cortex) and of cGMP-phosphodiesterase (lowest in cortex) in whole tissue homogenates. Soluble guanylate cyclase of cortex and inner medulla exhibited typical Michaelis-Menten kinetics with an apparent Km for MnGTP of 0.11 mM, while the particulate enzyme from inner medulla exhibited apparent positive cooperative behavior and a decreased dependence on Mn2+. Thus, the particulate enzyme could play a key role in regulating cGMP levels inthe intact cell where Mn2+ concentrations are low. The soluble and particulate enzymes from inner medulla were further distinguished by their responses to several test agents. The soluble enzyme was activated by Ca2+, NaN3, NaNo2 and phenylhydrazine, whereas particulate activity was inhibited by Ca2+ and was unresponsive to the latter agents. In the presence of NaNo2, Mn2+ requirement of the soluble enzyme was reduced and equivalent to that of the particulate preparation. Moreover, relative responsiveness of the sollble enzyme to NaNO2 was potentiated when Mg2+ replaced Mn2+ as the sole divalent cation. These changes in metal requirements may be involved in the action of NaNO2 to increase cGMP in intact kidney. Soluble guanylate cyclase of cortex was clearly more responsive to stimulation by NaN3, Nano2, and phenylhydrazine that was soluble activity from either medullary tissue. The effectiveness of the agonists on soluble activity from outer and inner medulla cound also be distinguished. Accordingly, regulation and properties of soluble guanylate cyclase, as well as subcellular enzyme distribution, and distinct in the three regions of the kidney."}
{"id": "PMID:10968", "title": "Thermal transitions of myosin and its helical fragments. Regions of structural instability in the myosin molecule.", "content": "The structural stabilities of all the familiar proteolytic fragments of myosin have been investigated in melting studies over the pH ranges 5.5-7.0 in 0.5 M KCl. All fragments except subfragment 2 undergo a melting transition manifested by the cooperative uptake of protons in the temperature range 34-47 degrees C, and these fragments experience an increase in transition temperature, Tm as the pH is increased. Subfragment 2 undergoes a melting transition in the 43-55 degrees C range, manifested by the dissociation of protons, and it experiences a decrease in Tm as the pH is increased. These results suggest that pH changes can modulate the relative stabilities of the light meromysin, subfragment-1, and subfragment-2 regions of the myosin molecule.", "contents": "Thermal transitions of myosin and its helical fragments. Regions of structural instability in the myosin molecule. The structural stabilities of all the familiar proteolytic fragments of myosin have been investigated in melting studies over the pH ranges 5.5-7.0 in 0.5 M KCl. All fragments except subfragment 2 undergo a melting transition manifested by the cooperative uptake of protons in the temperature range 34-47 degrees C, and these fragments experience an increase in transition temperature, Tm as the pH is increased. Subfragment 2 undergoes a melting transition in the 43-55 degrees C range, manifested by the dissociation of protons, and it experiences a decrease in Tm as the pH is increased. These results suggest that pH changes can modulate the relative stabilities of the light meromysin, subfragment-1, and subfragment-2 regions of the myosin molecule."}
{"id": "PMID:10969", "title": "Relative stabilities of the two quaternary conformations of human fetal hemoglobin.", "content": "The pH dependence of several functional properties of human fetal and adult hemoglobins have been studied to determine the relative stabilities of the high and low affinity (R and T) quaternary conformations of the two proteins under different conditions. Fetal aqumethemoglobin undergoes changes in sulfhydryl reactivity, absorption spectrum, and circular dichroism in the presence of insitol hexaphospahte which are consistent with a transition from the R to T quaternary state, but only at pH values below 6.8. In adult hemoglobin this transition can be induced pH values below 7.2. Even in the absence of phosphates, the ultraviolet (uv) circular dichroism spectrum of fetal aquomethemoglobin at low pH indicates the presence of some T conformation. The initial value for the second-order rate constant for combination of fetal deoxyhemoglobin with carbon monoxide is comparable to that for adult hemoglobin in the absence of organic phosphates and is not reduced by organic phosphates as much as that for the adult protein. The apparent first-order rate constant for dissociation of CO from fully liganded fetal hemoglobin, measured by replacement with NO, increases threefold in the absence of organic phosphates, and fourfold in the presence of organic phosphates, with decreasing pH; the midpoint of the pH dependent transition occurs around 6.8. A similar increase in the apparent first-order rate constant for O2 dissociation as measured by replacement with CO, can also be seen with decreasing pH. NO-hemoglobin F can be converted to the T state even when fully liganded simply by lowering the pH, as judged by uv circular dichroism, visible difference spectrum in the region of the alpha and beta bands, and a dramatic increase in the rate of NO dissociation, measured by replacement with CO in the presence of dithionite. These results are all consistent with a model for fetal hemoglobin in which the organic phosphate site may be functionally weakened by replacement of a residue involved in ionic interactions with the negatively charged phosphate groups, but in which the low affinity T conformation is intrinsically more stable than that of adllt hemoglobin. According to this model,the differences between fetal and adult hemoglobin can be accounted for primarily in terms of the relative stabilities of R and T conformations in each of the proteins with differences in the intrinsic properties of the individual conformations contributing effects of only secondary importance.", "contents": "Relative stabilities of the two quaternary conformations of human fetal hemoglobin. The pH dependence of several functional properties of human fetal and adult hemoglobins have been studied to determine the relative stabilities of the high and low affinity (R and T) quaternary conformations of the two proteins under different conditions. Fetal aqumethemoglobin undergoes changes in sulfhydryl reactivity, absorption spectrum, and circular dichroism in the presence of insitol hexaphospahte which are consistent with a transition from the R to T quaternary state, but only at pH values below 6.8. In adult hemoglobin this transition can be induced pH values below 7.2. Even in the absence of phosphates, the ultraviolet (uv) circular dichroism spectrum of fetal aquomethemoglobin at low pH indicates the presence of some T conformation. The initial value for the second-order rate constant for combination of fetal deoxyhemoglobin with carbon monoxide is comparable to that for adult hemoglobin in the absence of organic phosphates and is not reduced by organic phosphates as much as that for the adult protein. The apparent first-order rate constant for dissociation of CO from fully liganded fetal hemoglobin, measured by replacement with NO, increases threefold in the absence of organic phosphates, and fourfold in the presence of organic phosphates, with decreasing pH; the midpoint of the pH dependent transition occurs around 6.8. A similar increase in the apparent first-order rate constant for O2 dissociation as measured by replacement with CO, can also be seen with decreasing pH. NO-hemoglobin F can be converted to the T state even when fully liganded simply by lowering the pH, as judged by uv circular dichroism, visible difference spectrum in the region of the alpha and beta bands, and a dramatic increase in the rate of NO dissociation, measured by replacement with CO in the presence of dithionite. These results are all consistent with a model for fetal hemoglobin in which the organic phosphate site may be functionally weakened by replacement of a residue involved in ionic interactions with the negatively charged phosphate groups, but in which the low affinity T conformation is intrinsically more stable than that of adllt hemoglobin. According to this model,the differences between fetal and adult hemoglobin can be accounted for primarily in terms of the relative stabilities of R and T conformations in each of the proteins with differences in the intrinsic properties of the individual conformations contributing effects of only secondary importance."}
{"id": "PMID:10970", "title": "Adenine nucleotide metabolism of blood platelets. IX. Time course of secretion and changes in energy metabolism in thrombin-treated platelets.", "content": "Changes in the energy metabolism of washed human platelets were compared with the kinetics of secretion induced by thrombin (5 units/ml). A 50% decrease in the level of metabolic ATP (3H-labelled), which was essentially complete in 30s, was matched in rate by adenine nucleotide secretion from storage in dense granules. Incubation of platelets with antimycin before thrombin addition increased the rate of fall in metabolic ATP, but did not affect the rate of adenine nucleotide secretion. beta-N-Acetylglucosaminidase secretion, which was slower than adenine nucleotide secretion in control platelets, was noticeably inhibited by antimycin, confirming previous reports that different regulatory mechanisms exist for dense and alpha-granule secretion. The rates of rephosphorylation of metabolic ADP to ATP via glycolysis and oxidative phosphorylation were estimated by measuring lactate production and O2 consumption in resting and thrombin-stimulated platelets and compared to the level of metabolic ATP (9-10 nmol/mg of platelet protein in the resting state). The rate of ATP production was stimulated at least two fold from 12 nmol to 24 nmol/min/mg within seconds of thrombin addition. This increased rate was maintained over the observed period of 5 min although the level of metabolic ATP had decreased to 4-5 nmol/mg within 30 s; the turnover of the remaining metabolic ATP thus increased four fold over the resting state although the actual stimulation of energy production was only two fold.", "contents": "Adenine nucleotide metabolism of blood platelets. IX. Time course of secretion and changes in energy metabolism in thrombin-treated platelets. Changes in the energy metabolism of washed human platelets were compared with the kinetics of secretion induced by thrombin (5 units/ml). A 50% decrease in the level of metabolic ATP (3H-labelled), which was essentially complete in 30s, was matched in rate by adenine nucleotide secretion from storage in dense granules. Incubation of platelets with antimycin before thrombin addition increased the rate of fall in metabolic ATP, but did not affect the rate of adenine nucleotide secretion. beta-N-Acetylglucosaminidase secretion, which was slower than adenine nucleotide secretion in control platelets, was noticeably inhibited by antimycin, confirming previous reports that different regulatory mechanisms exist for dense and alpha-granule secretion. The rates of rephosphorylation of metabolic ADP to ATP via glycolysis and oxidative phosphorylation were estimated by measuring lactate production and O2 consumption in resting and thrombin-stimulated platelets and compared to the level of metabolic ATP (9-10 nmol/mg of platelet protein in the resting state). The rate of ATP production was stimulated at least two fold from 12 nmol to 24 nmol/min/mg within seconds of thrombin addition. This increased rate was maintained over the observed period of 5 min although the level of metabolic ATP had decreased to 4-5 nmol/mg within 30 s; the turnover of the remaining metabolic ATP thus increased four fold over the resting state although the actual stimulation of energy production was only two fold."}
{"id": "PMID:10971", "title": "Ammonia production and pathways of glutamine utilization in rat kidney slices.", "content": "Ammonia production from glutamine was studied in slices from non-acidotic and acidotic rat kidneys. Slices from non-acidotic kidneys made 53% as much ammonia from D-glutamine as from L-glutamine during the initial 15 min of incubation. Thereafter the production rate from the L-isomer accelerated while that from the D-isomer remained constant. The accelerated rate of ammonia production from L-glutamine was dependent upon tissue swelling since prevention of swelling reduced the production rate. Swelling activates the mitochondrial glutaminase I pathway as evidenced by the rise in ammonia produced per glutamine utilized ratio as well as by the accelerated rate of CO2 production derived from the oxidative disposal of glutamin's carbon skeleton. Cortical slice swelling activates the mitochondrial pathway in a manner not unlike that seen in vivo during chronic acidosis and may reflect increased permeability to glutamine. Acidotic rat kidneys are not swollen in vivo while cortical slices initially produce 4-fold more ammonia than do non-acidotic slices. After 15 min, this 4-fold difference in total ammonia production drops to only a 2-fold difference due to the swelling-induced activation of the mitochondrial pathway. Consequently, slice swelling obliterates the important fact that ammonia production by the mitochondrial pathway is 15-fold greater in acidotic than in non-acidotic kidneys.", "contents": "Ammonia production and pathways of glutamine utilization in rat kidney slices. Ammonia production from glutamine was studied in slices from non-acidotic and acidotic rat kidneys. Slices from non-acidotic kidneys made 53% as much ammonia from D-glutamine as from L-glutamine during the initial 15 min of incubation. Thereafter the production rate from the L-isomer accelerated while that from the D-isomer remained constant. The accelerated rate of ammonia production from L-glutamine was dependent upon tissue swelling since prevention of swelling reduced the production rate. Swelling activates the mitochondrial glutaminase I pathway as evidenced by the rise in ammonia produced per glutamine utilized ratio as well as by the accelerated rate of CO2 production derived from the oxidative disposal of glutamin's carbon skeleton. Cortical slice swelling activates the mitochondrial pathway in a manner not unlike that seen in vivo during chronic acidosis and may reflect increased permeability to glutamine. Acidotic rat kidneys are not swollen in vivo while cortical slices initially produce 4-fold more ammonia than do non-acidotic slices. After 15 min, this 4-fold difference in total ammonia production drops to only a 2-fold difference due to the swelling-induced activation of the mitochondrial pathway. Consequently, slice swelling obliterates the important fact that ammonia production by the mitochondrial pathway is 15-fold greater in acidotic than in non-acidotic kidneys."}
{"id": "PMID:10972", "title": "Effect of imidazole on renal gluconeogenesis.", "content": "The metabolic effects of imidazole were tested in rat renal cortex. Imidazole enhanced the activity of renal cortical phosphodiesterase in vitro. Imidazole inhibited glucose production in a dose-dependent fashion from a variety of substrates in the gluconeogenic pathway proximal to the triose phsophates. The stimulation in renal gluconeogenesis resulting from isoproterenol and parathyroid hormone was inhibited by imidazole. These changes correlated with an inhibition of the augmented levels of renal cortical cyclic AMP levels produced by these hormones. These studies indicate that imidazole is an effective activator of phosphodiesterase in intact renal cells and lend further support to the suggestion that the stimulation of renal gluconeogenesis produced by isoproterenol and parathyroid hormone is mediated by a release of cyclic AMP.", "contents": "Effect of imidazole on renal gluconeogenesis. The metabolic effects of imidazole were tested in rat renal cortex. Imidazole enhanced the activity of renal cortical phosphodiesterase in vitro. Imidazole inhibited glucose production in a dose-dependent fashion from a variety of substrates in the gluconeogenic pathway proximal to the triose phsophates. The stimulation in renal gluconeogenesis resulting from isoproterenol and parathyroid hormone was inhibited by imidazole. These changes correlated with an inhibition of the augmented levels of renal cortical cyclic AMP levels produced by these hormones. These studies indicate that imidazole is an effective activator of phosphodiesterase in intact renal cells and lend further support to the suggestion that the stimulation of renal gluconeogenesis produced by isoproterenol and parathyroid hormone is mediated by a release of cyclic AMP."}
{"id": "PMID:10973", "title": "Vitamin B-6-catalyzed beta-elimination of serine and O-phosphoserine. Qualitative and quantitative aspects of catalytic influences at the rate-limiting step, a comparison with the rate of enzymatic beta-elimination.", "content": "The overall reaction rates for the beta-elimination of serine and O-phosphoserine, catalyzed by various vitamin B-6 analogs (pyridoxal 5'-phosphate, 5'-deoxypyridoxal and N-methylpyridoxal 5'-phosphate) in the presence or absence of Cu2+ ions, are determined. The comparison of the pH-dependence of the molar activities of the three vitamin B-6 aldehydes in beta-elimination of serine enables the characterization of the different active Schiff base species and the single catalytic events. The Schiff base which has a positive charge on the pyridine ring nitrogen and a fully ionized phosphate group shows the highest molar activity. The phosphate group acts as an intramolecular general base catalyst, most probably at the alpha-carbon proton of the amino acid. Furthermore general acid catalysis by buffer species occurs at the beta-hydroxy group serine. These facts together provide a kinetically unambiguous description of the mechanism of the reaction: the removal of the proton at the alpha-carbon atom of serine is the rate-limiting step and is followed by the more rapid elimination of the b-hydroxy group of serine. The forward rate constant of the rate-limiting step is calculated for each of the reactions mentioned. The rate constants are compared with respect to the effectiveness of the individual catalytic components in the vitamin B-6-dependent beta-elimination. For optimal conditions the reaction of O-phosphoserine is faster by a factor of 10(4) in the velocity of the beta-elimination than the corresponding acid-catalyzed beta-elimination of serine. For the eliminations at the alpha- and beta-carbon atoms of O-phosphoserine in vitamin B-6-catalysed reactions a common transition state is discussed. From a comparison of the fastest vitamin beta-6-dependent model reaction with the rate of an enzymatic beta-elimination it is suggested that for those beta-elininating enzymes where the rate-limiting step is the same as in the model, the catalytic components mentioned could suffice to explain the velocity of the rate-limiting step.", "contents": "Vitamin B-6-catalyzed beta-elimination of serine and O-phosphoserine. Qualitative and quantitative aspects of catalytic influences at the rate-limiting step, a comparison with the rate of enzymatic beta-elimination. The overall reaction rates for the beta-elimination of serine and O-phosphoserine, catalyzed by various vitamin B-6 analogs (pyridoxal 5'-phosphate, 5'-deoxypyridoxal and N-methylpyridoxal 5'-phosphate) in the presence or absence of Cu2+ ions, are determined. The comparison of the pH-dependence of the molar activities of the three vitamin B-6 aldehydes in beta-elimination of serine enables the characterization of the different active Schiff base species and the single catalytic events. The Schiff base which has a positive charge on the pyridine ring nitrogen and a fully ionized phosphate group shows the highest molar activity. The phosphate group acts as an intramolecular general base catalyst, most probably at the alpha-carbon proton of the amino acid. Furthermore general acid catalysis by buffer species occurs at the beta-hydroxy group serine. These facts together provide a kinetically unambiguous description of the mechanism of the reaction: the removal of the proton at the alpha-carbon atom of serine is the rate-limiting step and is followed by the more rapid elimination of the b-hydroxy group of serine. The forward rate constant of the rate-limiting step is calculated for each of the reactions mentioned. The rate constants are compared with respect to the effectiveness of the individual catalytic components in the vitamin B-6-dependent beta-elimination. For optimal conditions the reaction of O-phosphoserine is faster by a factor of 10(4) in the velocity of the beta-elimination than the corresponding acid-catalyzed beta-elimination of serine. For the eliminations at the alpha- and beta-carbon atoms of O-phosphoserine in vitamin B-6-catalysed reactions a common transition state is discussed. From a comparison of the fastest vitamin beta-6-dependent model reaction with the rate of an enzymatic beta-elimination it is suggested that for those beta-elininating enzymes where the rate-limiting step is the same as in the model, the catalytic components mentioned could suffice to explain the velocity of the rate-limiting step."}
{"id": "PMID:10974", "title": "Properties and subcellular localization of CMP-N-acetylneuraminic acid hydrolase of calf kidney.", "content": "The properties and subcellular distribution of CMP-N-acetylneuraminic acid (CMP-NAcNeu) hydrolase were studied in the cortex of calf kidney. The pH optimum was 9.0 in both Tris - HCl and glycine/NaOH buffer. The apparent Km was 0.47 mM and the apparent V 15.3 mumol/h/g wet wt of calf kidney cortex. A stimulation by divalent metal ions (Ca2+ and Mg2+) was demonstrated for the hydrolase. In the presence of Triton X-100 an increase in enzyme activity was observed. CMP-NAcNeu hydrolase was inhibited by EDTA, beta-mercaptoethanol, nucleoside phosphates and nucleotide-sugars. The inhibition was more pronounced when a sub-optimal CMP-NAcNeu concentration was used. The enzyme appeared to be localized in the plasma membranes. In the plasma membrane preparation of calf kidney cortex, which was derived mainly from the proximal tubule cells, the yield of CMP-NAcNeu hydrolase (13%) and its increase in specific activity (9-fold) was as high as for the plasma membrane marker enzymes. From subcellular distribution studies it appeared that the enzyme was localized mainly at the bursh border side of the plasma membrane of the proximal tubule cell.", "contents": "Properties and subcellular localization of CMP-N-acetylneuraminic acid hydrolase of calf kidney. The properties and subcellular distribution of CMP-N-acetylneuraminic acid (CMP-NAcNeu) hydrolase were studied in the cortex of calf kidney. The pH optimum was 9.0 in both Tris - HCl and glycine/NaOH buffer. The apparent Km was 0.47 mM and the apparent V 15.3 mumol/h/g wet wt of calf kidney cortex. A stimulation by divalent metal ions (Ca2+ and Mg2+) was demonstrated for the hydrolase. In the presence of Triton X-100 an increase in enzyme activity was observed. CMP-NAcNeu hydrolase was inhibited by EDTA, beta-mercaptoethanol, nucleoside phosphates and nucleotide-sugars. The inhibition was more pronounced when a sub-optimal CMP-NAcNeu concentration was used. The enzyme appeared to be localized in the plasma membranes. In the plasma membrane preparation of calf kidney cortex, which was derived mainly from the proximal tubule cells, the yield of CMP-NAcNeu hydrolase (13%) and its increase in specific activity (9-fold) was as high as for the plasma membrane marker enzymes. From subcellular distribution studies it appeared that the enzyme was localized mainly at the bursh border side of the plasma membrane of the proximal tubule cell."}
{"id": "PMID:10975", "title": "Localization and some properties of lysosomal dipeptidases in rat liver.", "content": "1. The rates of hydrolysis of 26 synthetic dipeptides by extracts from highly purified lysosomal fractions from rat liver at pH 5.0 and by whole liver homogenates at pH 7.4 have been determined. Extracts from the lysosomal fractions hydrolysed most peptides at a lower rate per mg protein than the homogenates, and some peptides not at all. 2. Properties of two dipeptidases present in the extracts from the lysosomal fractions, splitting Ile-Glu and Leu-Gly, respectively, were studied in greater detail. The enzyme that hydrolysed Ile-Glu was strongly activated by dithiothreitol, showed optimal activity at pH 4.5 and had a molecular weight of about 120 000. Leu-Gly dipeptidase did apparently not contain an essential thiol group and had a molecular weight of approx. 90 000. It showed maximal activity at pH 6.5. 3. After differential centrifugation of liver homogenates, Ile-Glu and Leu-Gly-splitting activities were determined in the fractions, under the optimal conditions mentioned above. The Ile-Glu-hydrolysing enzyme activity showed about the same distribution as the lysosomal marker enzyme acid phosphatase. Leu-Gly-splitting activity, however, was largely present in the cytosol fraction, with only a small peak in the lysosomal fraction. We obtained evidence that the activities present in the lysosomal fraction and in the cytosol fraction were due to different enzymes, and that one of these enzymes was localized exclusively in lysosomes. 4. It is concluded that some dipeptides originating from intralysosomal proteolysis might be split by lysosomal dipeptidases, whereas others are probably hydrolysed only in the extra-lysosomal compartment of the cell.", "contents": "Localization and some properties of lysosomal dipeptidases in rat liver. 1. The rates of hydrolysis of 26 synthetic dipeptides by extracts from highly purified lysosomal fractions from rat liver at pH 5.0 and by whole liver homogenates at pH 7.4 have been determined. Extracts from the lysosomal fractions hydrolysed most peptides at a lower rate per mg protein than the homogenates, and some peptides not at all. 2. Properties of two dipeptidases present in the extracts from the lysosomal fractions, splitting Ile-Glu and Leu-Gly, respectively, were studied in greater detail. The enzyme that hydrolysed Ile-Glu was strongly activated by dithiothreitol, showed optimal activity at pH 4.5 and had a molecular weight of about 120 000. Leu-Gly dipeptidase did apparently not contain an essential thiol group and had a molecular weight of approx. 90 000. It showed maximal activity at pH 6.5. 3. After differential centrifugation of liver homogenates, Ile-Glu and Leu-Gly-splitting activities were determined in the fractions, under the optimal conditions mentioned above. The Ile-Glu-hydrolysing enzyme activity showed about the same distribution as the lysosomal marker enzyme acid phosphatase. Leu-Gly-splitting activity, however, was largely present in the cytosol fraction, with only a small peak in the lysosomal fraction. We obtained evidence that the activities present in the lysosomal fraction and in the cytosol fraction were due to different enzymes, and that one of these enzymes was localized exclusively in lysosomes. 4. It is concluded that some dipeptides originating from intralysosomal proteolysis might be split by lysosomal dipeptidases, whereas others are probably hydrolysed only in the extra-lysosomal compartment of the cell."}
{"id": "PMID:10976", "title": "Some properties of erythrocuprein treated by organic solvents.", "content": "The effect of various types of organic solvents on the properties of bovine erythrocuprein was studied. Three organic solvents were found in which the protein is soluble, these were: dimethyl sulfoxide, formamide and N-methylformamide. It was shown that in formamide and dimethyl sulfoxide media the protein possees superoxide dismutase activity, but in N-methylformamide the protein has negligible activity. In organic solvents the substrate (superoxide radical) and solvated electron result in reduction of the protein copper. At high concentrations of superoxide radical or solvated electrons an inactivation of protein and stabilization of superoxide radicals was noted. The stabilization is most pronounced in N-methylformamide. The protein that is reduced by the radical or the solvated electron may be reoxidized by molecular oxygen, the latter being reduced to the superoxide radical.", "contents": "Some properties of erythrocuprein treated by organic solvents. The effect of various types of organic solvents on the properties of bovine erythrocuprein was studied. Three organic solvents were found in which the protein is soluble, these were: dimethyl sulfoxide, formamide and N-methylformamide. It was shown that in formamide and dimethyl sulfoxide media the protein possees superoxide dismutase activity, but in N-methylformamide the protein has negligible activity. In organic solvents the substrate (superoxide radical) and solvated electron result in reduction of the protein copper. At high concentrations of superoxide radical or solvated electrons an inactivation of protein and stabilization of superoxide radicals was noted. The stabilization is most pronounced in N-methylformamide. The protein that is reduced by the radical or the solvated electron may be reoxidized by molecular oxygen, the latter being reduced to the superoxide radical."}
{"id": "PMID:10977", "title": "Oxygen equilibrium characteristics of adult and fetal hemoglobin of Japanese monkey (Macaca fuscata).", "content": "Adult hemoglobin and fetal hemoglobin were obtained from Japanese monkey (Macaca fuscata) and their oxygen equilibrium characteristics were studied. (1) The oxygen affinity of fetal hemoglobin was higher than that of adult hemoglobin both in the presence and absence of 2,3-diphosphoglycerate. The presence of diphosphoglycerate lowers the oxygen affinity of adult hemoglobin much greater than does that of HbF and the diphosphoglycerate levels of red cells of adult and newborn monkeys are about the same. (2) The intensity of the Bohr effect, as expressed by -deltalogP50/deltapH, at pH 7.4 was in the order of fetal hemoglobin-diphosphoglycerate greater than adult hemoglobin-diphosphoglycerate greater than fetal hemoglobin greater than adult hemoglobin.", "contents": "Oxygen equilibrium characteristics of adult and fetal hemoglobin of Japanese monkey (Macaca fuscata). Adult hemoglobin and fetal hemoglobin were obtained from Japanese monkey (Macaca fuscata) and their oxygen equilibrium characteristics were studied. (1) The oxygen affinity of fetal hemoglobin was higher than that of adult hemoglobin both in the presence and absence of 2,3-diphosphoglycerate. The presence of diphosphoglycerate lowers the oxygen affinity of adult hemoglobin much greater than does that of HbF and the diphosphoglycerate levels of red cells of adult and newborn monkeys are about the same. (2) The intensity of the Bohr effect, as expressed by -deltalogP50/deltapH, at pH 7.4 was in the order of fetal hemoglobin-diphosphoglycerate greater than adult hemoglobin-diphosphoglycerate greater than fetal hemoglobin greater than adult hemoglobin."}
{"id": "PMID:10978", "title": "Studies on the binding of FMN by apoflavodoxin from Peptostreptococcus elsdenii, pH and NaCl concentration dependence.", "content": "1. The pH and ionic strength dependence of the interaction of FMN with apoflavodoxin has been studied by fluorometry in the pH region 2-5, at 22 degrees C. 2. The rate constant of dissociation and the dissociation constant were experimentally determined; the rate constants of association were claculated at a given pH value. These constants depend on the ionic strength. The plots of these constants against the square root of the ionic strength are straight. 3. Our data have been interpreted in terms of the Br\u00f6nsted theory, which relates chemical reaction rates to ionic strength. The data indicate that the apoenzyme reaches its maximum net positive charge at pH 2.0-2.6. The calculated net charge in this pH region is between 11 and 12 and is in agreement with the theoretical value of 12 as deduced from the primary structure of the protein. The isoelectric point of the holoenzyme is about 4. 4. The rate constant of association extrapolated to zero ionic strength is 3.2-10(5)M-1-s-1 and is pH-independent. 5. The rate constant of dissociation and the dissociation constant extrapolated to zero ionic strength depend on the pH. The results are explained by assuming that there are two protein ionizations with a pK value of 3.4; these ionizing groups are possibly close to the FMN binding site.", "contents": "Studies on the binding of FMN by apoflavodoxin from Peptostreptococcus elsdenii, pH and NaCl concentration dependence. 1. The pH and ionic strength dependence of the interaction of FMN with apoflavodoxin has been studied by fluorometry in the pH region 2-5, at 22 degrees C. 2. The rate constant of dissociation and the dissociation constant were experimentally determined; the rate constants of association were claculated at a given pH value. These constants depend on the ionic strength. The plots of these constants against the square root of the ionic strength are straight. 3. Our data have been interpreted in terms of the Br\u00f6nsted theory, which relates chemical reaction rates to ionic strength. The data indicate that the apoenzyme reaches its maximum net positive charge at pH 2.0-2.6. The calculated net charge in this pH region is between 11 and 12 and is in agreement with the theoretical value of 12 as deduced from the primary structure of the protein. The isoelectric point of the holoenzyme is about 4. 4. The rate constant of association extrapolated to zero ionic strength is 3.2-10(5)M-1-s-1 and is pH-independent. 5. The rate constant of dissociation and the dissociation constant extrapolated to zero ionic strength depend on the pH. The results are explained by assuming that there are two protein ionizations with a pK value of 3.4; these ionizing groups are possibly close to the FMN binding site."}
{"id": "PMID:10979", "title": "Alkalin titrations of human somatotropin, human choriomammotropin and ovine prolactin by circular dichroism and fluorescence.", "content": "Structural transitions occurring during the alkalin titration of human somatotropin, human choriomammotropin, and ovine prolactin have been investigated by means of circular dichroism and fluorescence emission spectra. Human somatotropin exhibited an isodichroic point at 287 nm, with all spectral changes being reversed upon back titration from pH 12.50 to pH 8.0. Fluorescence quenching as a function of pH produced a simple sigmoidal curve. Human choriomammotropin exhibited an isodichroic point at 288 nm. The fluorescence and circular dichroism spectra of this protein were found to be reversible between pH 8.0 and 11.0. However, on titration above pH 11, the isodichroic point and the reversibility of the circular dichroism spectra were lost. This conformational transition was accompanied by a sharp increase in fluorescence quantum yield. The circular dichroism spectra of ovine prolactin showed essentially no change on titration to pH 11.0. However, between pH 11.0 and 12.0, a sharp conformational transition was observed similar to that seen in human choriomammotropin, but not exhibiting the same increase in fluorescence quantum yield. The fluorescence titration of prolactin was found to be essentially reversible upon back titration from pH 12.5, although the circular dichroism spectra were not reversible from this pH.", "contents": "Alkalin titrations of human somatotropin, human choriomammotropin and ovine prolactin by circular dichroism and fluorescence. Structural transitions occurring during the alkalin titration of human somatotropin, human choriomammotropin, and ovine prolactin have been investigated by means of circular dichroism and fluorescence emission spectra. Human somatotropin exhibited an isodichroic point at 287 nm, with all spectral changes being reversed upon back titration from pH 12.50 to pH 8.0. Fluorescence quenching as a function of pH produced a simple sigmoidal curve. Human choriomammotropin exhibited an isodichroic point at 288 nm. The fluorescence and circular dichroism spectra of this protein were found to be reversible between pH 8.0 and 11.0. However, on titration above pH 11, the isodichroic point and the reversibility of the circular dichroism spectra were lost. This conformational transition was accompanied by a sharp increase in fluorescence quantum yield. The circular dichroism spectra of ovine prolactin showed essentially no change on titration to pH 11.0. However, between pH 11.0 and 12.0, a sharp conformational transition was observed similar to that seen in human choriomammotropin, but not exhibiting the same increase in fluorescence quantum yield. The fluorescence titration of prolactin was found to be essentially reversible upon back titration from pH 12.5, although the circular dichroism spectra were not reversible from this pH."}
{"id": "PMID:10980", "title": "A pH-dependent conformational change in the coat protein subunits from potato virus X.", "content": "Both the circular dichroism and fluorescence spectra of the dissociated coat protein subunits from potato virus X changed substantially over the pH range 8 to 4, irreversible changes resulted below pH 4, with tyrosyl and tryptophanyl residues affected most. The titration curves show a pKa of about 5.6 and do not require cooperative interactions between the coat protein subunits, thus they are in marked contrast to titrations of tobacco mosaic virus A-protein. The spectra of the intact virus were little changed between pH 8 and 4 and suggested that the coat protein was locked into a conformation similar to that of the subunits in solution at pH 7. It is proposed that the pH induced conformational change is responsible for determining the acidic branch of the pH profile for reconstitution of potato virus X from its dissociated coat protein subunits and RNA.", "contents": "A pH-dependent conformational change in the coat protein subunits from potato virus X. Both the circular dichroism and fluorescence spectra of the dissociated coat protein subunits from potato virus X changed substantially over the pH range 8 to 4, irreversible changes resulted below pH 4, with tyrosyl and tryptophanyl residues affected most. The titration curves show a pKa of about 5.6 and do not require cooperative interactions between the coat protein subunits, thus they are in marked contrast to titrations of tobacco mosaic virus A-protein. The spectra of the intact virus were little changed between pH 8 and 4 and suggested that the coat protein was locked into a conformation similar to that of the subunits in solution at pH 7. It is proposed that the pH induced conformational change is responsible for determining the acidic branch of the pH profile for reconstitution of potato virus X from its dissociated coat protein subunits and RNA."}
{"id": "PMID:10981", "title": "On the allosteric transition between the structures of high and low ligand affinity in carp hemoglobin.", "content": "The variation of magneto-optical rotatory dispersion with pH for carp deoxyhemoglobin in the presence and absence of inositol hexaphosphate was interpreted as a pH-induced allosteric transition between the structures of high and low ligand affinity (the R and T states in terms of the two state model of cooperativity). Increasing the pH from 6 to 11 causes a decrease in the fraction of molecules in the T state from 1 to 0.65. In the absence of inositol hexaphosphate the pH dependence of this fraction has a midpoint at 7.8, addition of inositol hexaphosphate shifts this midpoint by 1.5 units toward high pH. From the analysis of the data obtained and the pH dependences of functional properties (Tan, A.L., Noble, R.W. and Gibson, Q.H. (1973) J. Biol. Chem. 248, 2880-2888) the parameters of the two state model of cooperativity for carp hemoglobin were estimated.", "contents": "On the allosteric transition between the structures of high and low ligand affinity in carp hemoglobin. The variation of magneto-optical rotatory dispersion with pH for carp deoxyhemoglobin in the presence and absence of inositol hexaphosphate was interpreted as a pH-induced allosteric transition between the structures of high and low ligand affinity (the R and T states in terms of the two state model of cooperativity). Increasing the pH from 6 to 11 causes a decrease in the fraction of molecules in the T state from 1 to 0.65. In the absence of inositol hexaphosphate the pH dependence of this fraction has a midpoint at 7.8, addition of inositol hexaphosphate shifts this midpoint by 1.5 units toward high pH. From the analysis of the data obtained and the pH dependences of functional properties (Tan, A.L., Noble, R.W. and Gibson, Q.H. (1973) J. Biol. Chem. 248, 2880-2888) the parameters of the two state model of cooperativity for carp hemoglobin were estimated."}
{"id": "PMID:10982", "title": "The kinetics of the reduction of cytochrome c by the superoxide anion radical.", "content": "1. At neutral pH ferricytochrome c is reduced by the superoxide anion radical (O2-), without loss of enzymatic activity, by a second order process in which no intermediates are observed. The yield of ferrocytochrome c (82-104%), as related to the amount of O2- produced, is slightly dependent on the concentration of sodium formate in the matrix solution. 2. The reaction (k1 equals (1.1+/-0.1) - 10(6) M-1 - s-1 at pH 7.2, I equals 4 mM and 21 degrees C) can be inhibited by superoxide dismutase and trace amounts of copper ions. The inhibition by copper ions is removed by EDTA without interference in the O2- reduction reaction. 3. The second-order rate constant for the reaction of O2- with ferricytochrome c depends on the pH of the matrix solution, decreasing rapidly at pH greater than 8. The dependence of the rate constant on the pH can be explained by assuming that only the neutral form of ferricytochrome c reacts with O2- and that the alkaline form of the hemoprotein is unreactive. From studies at pH 8.9, the rate for the transition from the alkaline to the neutral form of ferricytochrome c can be estimated to be 0.3 s-1 (at 21 degrees C and I equals 4 mM). 4. The second-order rate constant for the reaction of O2- with ferricytochrome c is also dependent on the ionic strength of the medium. From a plot of log k1 versus I1/2-(I + alphaI1/2)-1 we determined the effective charge on the ferricytochrome c molecule as +6.3 and the rate constant at I equals 0 as (3.1+/-0.1) - 10(6) M-1 - s-1 (pH 7.1, 21 degrees C). 5. The possibility that singlet oxygen is formed as a product of the reaction of O2- with ferricytochrome c can be ruled out on thermodynamic grounds.", "contents": "The kinetics of the reduction of cytochrome c by the superoxide anion radical. 1. At neutral pH ferricytochrome c is reduced by the superoxide anion radical (O2-), without loss of enzymatic activity, by a second order process in which no intermediates are observed. The yield of ferrocytochrome c (82-104%), as related to the amount of O2- produced, is slightly dependent on the concentration of sodium formate in the matrix solution. 2. The reaction (k1 equals (1.1+/-0.1) - 10(6) M-1 - s-1 at pH 7.2, I equals 4 mM and 21 degrees C) can be inhibited by superoxide dismutase and trace amounts of copper ions. The inhibition by copper ions is removed by EDTA without interference in the O2- reduction reaction. 3. The second-order rate constant for the reaction of O2- with ferricytochrome c depends on the pH of the matrix solution, decreasing rapidly at pH greater than 8. The dependence of the rate constant on the pH can be explained by assuming that only the neutral form of ferricytochrome c reacts with O2- and that the alkaline form of the hemoprotein is unreactive. From studies at pH 8.9, the rate for the transition from the alkaline to the neutral form of ferricytochrome c can be estimated to be 0.3 s-1 (at 21 degrees C and I equals 4 mM). 4. The second-order rate constant for the reaction of O2- with ferricytochrome c is also dependent on the ionic strength of the medium. From a plot of log k1 versus I1/2-(I + alphaI1/2)-1 we determined the effective charge on the ferricytochrome c molecule as +6.3 and the rate constant at I equals 0 as (3.1+/-0.1) - 10(6) M-1 - s-1 (pH 7.1, 21 degrees C). 5. The possibility that singlet oxygen is formed as a product of the reaction of O2- with ferricytochrome c can be ruled out on thermodynamic grounds."}
{"id": "PMID:10983", "title": "Algal glyceraldehyde-3-phosphate dehydrogenases. Conversion of the NADH-linked enzyme of Scenedesmus obliquus into a form which preferentially uses NADPH as coenzyme.", "content": "Scenedesmus obliquus contains two glyceraldehyde-3-phosphate dehydrogenases (EC 1.2.1.-) one of which uses NADH as its preferred coenzyme (D-enzyme) and the other NADPH (T-enzyme). On incubation of the D-enzyme with cysteine and a 1,3-diphosphoglycerate-generating system the specific activity with NADH as coenzyme decreased whilst that with NADPH increased by a factor of 10. The components of the generating system had no effect on the D-enzyme individually and it is concluded that 1,3-diphosphoglycerate was probably responsible for the change in nucleotide specificity. The coenzyme specificity of the T-enzyme was not affected by such treatment. A similar type of activation occurred to a lesser extent on incubation of the D-enzyme with 2,3-diphosphoglycerate. The NADPH-dependent activity of the D-enzyme could also be promoted by incubation with NADPH. However, in this case the activation was less than that seen with either 1,3- or 2,3-diphosphoglycerate. The change in coenzyme specificity of the D-enzyme occurred in parallel with changes in sedimentation behaviour. Initially, a single boundary of S20,w equals 14.5 S was present, but on conversion to NADPH-dependent activity by incubation with the 1,3-diphosphoglycerate-generating system, new boundaries of 7.5 S and 5.5 S appeared. The first of these corresponds in sedimentation coefficient to the native T-enzyme. On removal of 1,3-diphosphoglycerate the 7.5 S boundary disappeared accompanied by an increase in that of 14.5 S, whilst the 5.5 S boundary persisted. These changes are consistent with the reversible conversion of the D-enzyme into a form similar to the native T-enzyme in response to cysteine and 1,3-diphosphoglycerate. These effects may be explained if acylation of the active site of the D-enzyme by 1,3-diphosphoglycerate results in displacement of the bound nucleotide, thus promoting nucleotide exchange. These findings are consistent with the kinetic mechanism established for other glyceraldehyde-3-phosphate dehydrogenases. Similar activation was seen in extracts of other species of the Chlorophyta but not in other photosynthetic organisms. The significance of this type of activation of enzyme activity to the metabolism of these species of algae is discussed.", "contents": "Algal glyceraldehyde-3-phosphate dehydrogenases. Conversion of the NADH-linked enzyme of Scenedesmus obliquus into a form which preferentially uses NADPH as coenzyme. Scenedesmus obliquus contains two glyceraldehyde-3-phosphate dehydrogenases (EC 1.2.1.-) one of which uses NADH as its preferred coenzyme (D-enzyme) and the other NADPH (T-enzyme). On incubation of the D-enzyme with cysteine and a 1,3-diphosphoglycerate-generating system the specific activity with NADH as coenzyme decreased whilst that with NADPH increased by a factor of 10. The components of the generating system had no effect on the D-enzyme individually and it is concluded that 1,3-diphosphoglycerate was probably responsible for the change in nucleotide specificity. The coenzyme specificity of the T-enzyme was not affected by such treatment. A similar type of activation occurred to a lesser extent on incubation of the D-enzyme with 2,3-diphosphoglycerate. The NADPH-dependent activity of the D-enzyme could also be promoted by incubation with NADPH. However, in this case the activation was less than that seen with either 1,3- or 2,3-diphosphoglycerate. The change in coenzyme specificity of the D-enzyme occurred in parallel with changes in sedimentation behaviour. Initially, a single boundary of S20,w equals 14.5 S was present, but on conversion to NADPH-dependent activity by incubation with the 1,3-diphosphoglycerate-generating system, new boundaries of 7.5 S and 5.5 S appeared. The first of these corresponds in sedimentation coefficient to the native T-enzyme. On removal of 1,3-diphosphoglycerate the 7.5 S boundary disappeared accompanied by an increase in that of 14.5 S, whilst the 5.5 S boundary persisted. These changes are consistent with the reversible conversion of the D-enzyme into a form similar to the native T-enzyme in response to cysteine and 1,3-diphosphoglycerate. These effects may be explained if acylation of the active site of the D-enzyme by 1,3-diphosphoglycerate results in displacement of the bound nucleotide, thus promoting nucleotide exchange. These findings are consistent with the kinetic mechanism established for other glyceraldehyde-3-phosphate dehydrogenases. Similar activation was seen in extracts of other species of the Chlorophyta but not in other photosynthetic organisms. The significance of this type of activation of enzyme activity to the metabolism of these species of algae is discussed."}
{"id": "PMID:10984", "title": "The uptake of choline by rat liver mitochondria.", "content": "1. Rat liver mitochondria can accumulate choline against a concentration gradient. Maximally about 30 nmol choline per mg mitochondrial protein are found in the matrix space. 2. The process of choline uptake is biphasic. After a rapid uptake of 1.5-15 nmol per mg protein, a slower uptake occurs if an energy supply is present. In the absence of energy, only the rapid uptake is found. 3. The inhibition of uncoupler-stimulated choline oxidation by cations is the result of an inhibition of choline uptake.", "contents": "The uptake of choline by rat liver mitochondria. 1. Rat liver mitochondria can accumulate choline against a concentration gradient. Maximally about 30 nmol choline per mg mitochondrial protein are found in the matrix space. 2. The process of choline uptake is biphasic. After a rapid uptake of 1.5-15 nmol per mg protein, a slower uptake occurs if an energy supply is present. In the absence of energy, only the rapid uptake is found. 3. The inhibition of uncoupler-stimulated choline oxidation by cations is the result of an inhibition of choline uptake."}
{"id": "PMID:10985", "title": "3alpha-, 7alpha- and 12alpha-hydroxysteroid dehydrogenase activities from Clostridium perfringens.", "content": "25 strains of Clostridium perfringens were screened for hydroxysteroid dehydrogenase activity; 19 contained NADP-dependent 3alpha-hydroxysteroid dehydrogenase and eight contained NAD-dependent 12alpha-hydroxysteroid dehydrogenase active against conjugated and unconjugated bile salts. All strains containing 12alpha-hydroxysteroid dehydrogenase also contained 3alpha-hydroxysteroid dehydrogenase although 12alpha-hydroxysteroid dehydrogenase was invariably in lesser quantity than the 3alpha-hydroxysteroid dehydrogenase. In addition, 7alpha-hydroxysteroid dehydrogenase activity was evident only when 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholanoate was substrate but notably absent when 3alpha, 7alpha-dihydroxy-5beta-cholanoate was substrate. The oxidation product 12alpha-hydroxy-3, 7-diketo-5beta-cholanoate is rapidly further degraded to an unknown compound devoid of either 3alpha- or 7alpha-OH groups. Group specificity of these enzymes was confirmed by thin-layer chromatography studies of the oxidation products. These enzyme systems appear to be constitutive rather than inducible. In contrast to C. perfringens. Clostridium paraputrificum (five strains tested) contained no measurable hydroxysteroid dehydrogenase activity. pH studies of the C. perfringens enzymes revealed a sharp pH optimum at pH 11.3 and 10.5 for the 3alpha-OH- and 12alpha-OH-oriented activities, respectively. Kinetic studies gave Km estimates of approx. 5 X 10(-5) and 8 X 10(-4) M with 3alpha, 7a-dihydroxy-5beta-cholanoate and 3alpha, 12alpha-dihydroxy-5beta-cholanoate as substrates for two respective enzymes. 3alpha-hydroxysteroid dehydrogenase was active against 3alpha-OH-containing steroids such as androsterone regardless of the sterochemistry of the 5H (Both A/B cis and A/B trans steroides were substrates). There was no activity against 3beta-OH-containing steroids. The 3alpha- and 12alpha-hydroxysteroid dehydrogenase activities, although differing in cofactor requirements cannot be distinguished by their appearance in the growth curve, their mobility on disc gel electrophoresis, elution volume on passage through Sephadex G-200 or heat inactivation studies.", "contents": "3alpha-, 7alpha- and 12alpha-hydroxysteroid dehydrogenase activities from Clostridium perfringens. 25 strains of Clostridium perfringens were screened for hydroxysteroid dehydrogenase activity; 19 contained NADP-dependent 3alpha-hydroxysteroid dehydrogenase and eight contained NAD-dependent 12alpha-hydroxysteroid dehydrogenase active against conjugated and unconjugated bile salts. All strains containing 12alpha-hydroxysteroid dehydrogenase also contained 3alpha-hydroxysteroid dehydrogenase although 12alpha-hydroxysteroid dehydrogenase was invariably in lesser quantity than the 3alpha-hydroxysteroid dehydrogenase. In addition, 7alpha-hydroxysteroid dehydrogenase activity was evident only when 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholanoate was substrate but notably absent when 3alpha, 7alpha-dihydroxy-5beta-cholanoate was substrate. The oxidation product 12alpha-hydroxy-3, 7-diketo-5beta-cholanoate is rapidly further degraded to an unknown compound devoid of either 3alpha- or 7alpha-OH groups. Group specificity of these enzymes was confirmed by thin-layer chromatography studies of the oxidation products. These enzyme systems appear to be constitutive rather than inducible. In contrast to C. perfringens. Clostridium paraputrificum (five strains tested) contained no measurable hydroxysteroid dehydrogenase activity. pH studies of the C. perfringens enzymes revealed a sharp pH optimum at pH 11.3 and 10.5 for the 3alpha-OH- and 12alpha-OH-oriented activities, respectively. Kinetic studies gave Km estimates of approx. 5 X 10(-5) and 8 X 10(-4) M with 3alpha, 7a-dihydroxy-5beta-cholanoate and 3alpha, 12alpha-dihydroxy-5beta-cholanoate as substrates for two respective enzymes. 3alpha-hydroxysteroid dehydrogenase was active against 3alpha-OH-containing steroids such as androsterone regardless of the sterochemistry of the 5H (Both A/B cis and A/B trans steroides were substrates). There was no activity against 3beta-OH-containing steroids. The 3alpha- and 12alpha-hydroxysteroid dehydrogenase activities, although differing in cofactor requirements cannot be distinguished by their appearance in the growth curve, their mobility on disc gel electrophoresis, elution volume on passage through Sephadex G-200 or heat inactivation studies."}
{"id": "PMID:10986", "title": "Studies on phosphatidylinositol phosphodiesterase (phospholipase C type) of Bacillus cereus. I. purification, properties and phosphatase-releasing activity.", "content": "A phosphatidylinositol phosphodiesterase from the culture broth of Bacillus cereus, was purified to a homogeneous state as indicated by polyacrylamide gel electrophoresis, by ammonium sulfate precipitation and chromatography with DEAE-cellulose and CM-Sephadex. The enzyme (molecular weight: 29000 +/- 1000) was maximally active at pH 7.2-7.5, AND NOT INFLUENCED BY EDTA, ophenanthroline, monoiodoacetate, p-chloromercuribenzoate or reduced glutathione. The enzyme specifically hydrolyzed phosphatidylinositol, but did not act on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, under the conditions examined. The products from phosphatidylinositol of enzyme reaction were diacylglycerols and a mixture of myoinositol 1- and 1, 2-cyclic phosphates, suggesting that the enzyme was a phosphatidylinositol-specific phospholipase C. The enzyme released alkaline phosphatase quantitatively from rat kidney slices. A kinetic analysis was made on the release of alkaline phosphatase. The results suggest that phosphatidylinositol-specific phospholipase C can specifically act on plasma membrane of rat kidney slices.", "contents": "Studies on phosphatidylinositol phosphodiesterase (phospholipase C type) of Bacillus cereus. I. purification, properties and phosphatase-releasing activity. A phosphatidylinositol phosphodiesterase from the culture broth of Bacillus cereus, was purified to a homogeneous state as indicated by polyacrylamide gel electrophoresis, by ammonium sulfate precipitation and chromatography with DEAE-cellulose and CM-Sephadex. The enzyme (molecular weight: 29000 +/- 1000) was maximally active at pH 7.2-7.5, AND NOT INFLUENCED BY EDTA, ophenanthroline, monoiodoacetate, p-chloromercuribenzoate or reduced glutathione. The enzyme specifically hydrolyzed phosphatidylinositol, but did not act on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, under the conditions examined. The products from phosphatidylinositol of enzyme reaction were diacylglycerols and a mixture of myoinositol 1- and 1, 2-cyclic phosphates, suggesting that the enzyme was a phosphatidylinositol-specific phospholipase C. The enzyme released alkaline phosphatase quantitatively from rat kidney slices. A kinetic analysis was made on the release of alkaline phosphatase. The results suggest that phosphatidylinositol-specific phospholipase C can specifically act on plasma membrane of rat kidney slices."}
{"id": "PMID:10987", "title": "Properties of triacylglycerol lipase in a mitochondrial fraction from baker's yeast (Saccharomyces cerevisiae).", "content": "A triacylglycerol lipase in a mitochondrial fraction isolated from yeast (Saccharomyces cerevisiae) has been characterized and the hydrolysis studied kinetically using an insoluble artificial triacylglycerol suspension. 1. The triacylglycerol was hydrolyzed almost completely to fatty acids and glycerol. The lipase activity was inhibited by potassium fluoride and the sodium salts of -chloride, -glycocholate and -pyrophosphate as well as by protamine sulfate but at concentrations much too high to indicate that the lipase is a non specific esterase or a lipoprotein lipase. Also parachloromercuribenzoate inhibited the lipase activity. Inhibitory effect of fatty acid was observed at concentrations above 1mM. This inhibition may provide a regulatory mechanism of the lipase in vivo. 2. On the day of isolation the lipase activity of intact mitochondria at pH 7.5 and 30 degrees C was 400 nmol free fatty acid -h-1 - mg-1 at a triacylglycerol concentration of 9.0 mM. Sonication of the mitochondria increased the activity 2-3 fold. Freezing of the mitochondria also activated the lipase and this activation was dependent upon the freezing method, the concentration of mitochondrial protein and the presence of bovine serum albumin. 3. The particulate nature of the assay system was illustrated by the observation that the apparent Km value of the lipase increased with the concentration of mitochondrial protein. For each protein concentration the lipase had two apparent Km values when the activity was assayed with intact mitochondria, but only one when  assayed with submitochondrial particles. At the same protein concentration the Km value for the latter was identical with the \"low affinity\" Km for the lipase in intact mitochondria.", "contents": "Properties of triacylglycerol lipase in a mitochondrial fraction from baker's yeast (Saccharomyces cerevisiae). A triacylglycerol lipase in a mitochondrial fraction isolated from yeast (Saccharomyces cerevisiae) has been characterized and the hydrolysis studied kinetically using an insoluble artificial triacylglycerol suspension. 1. The triacylglycerol was hydrolyzed almost completely to fatty acids and glycerol. The lipase activity was inhibited by potassium fluoride and the sodium salts of -chloride, -glycocholate and -pyrophosphate as well as by protamine sulfate but at concentrations much too high to indicate that the lipase is a non specific esterase or a lipoprotein lipase. Also parachloromercuribenzoate inhibited the lipase activity. Inhibitory effect of fatty acid was observed at concentrations above 1mM. This inhibition may provide a regulatory mechanism of the lipase in vivo. 2. On the day of isolation the lipase activity of intact mitochondria at pH 7.5 and 30 degrees C was 400 nmol free fatty acid -h-1 - mg-1 at a triacylglycerol concentration of 9.0 mM. Sonication of the mitochondria increased the activity 2-3 fold. Freezing of the mitochondria also activated the lipase and this activation was dependent upon the freezing method, the concentration of mitochondrial protein and the presence of bovine serum albumin. 3. The particulate nature of the assay system was illustrated by the observation that the apparent Km value of the lipase increased with the concentration of mitochondrial protein. For each protein concentration the lipase had two apparent Km values when the activity was assayed with intact mitochondria, but only one when  assayed with submitochondrial particles. At the same protein concentration the Km value for the latter was identical with the \"low affinity\" Km for the lipase in intact mitochondria."}
{"id": "PMID:10988", "title": "Properties of microsomal phospholipases in rat liver and hepatoma.", "content": "Phospholipase A1, A2 and lysophospholipase activities in microsomes of Novikoff hepatoma host rat liver and regenerating rat liver were compared using 1-[9', 10'-3H2]palmitoyl-2-[1'-14C] linoleoyl-sn-glycero-3-phosphoethanolamine, 1-[1' -3H-]hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamine, and 1-[9', 10'-3H2]palmitoyl-sn-glycero-3-phosphoethanolamine as substrates. 1. Microsomes of all three tissues showed two pH dependent peaks of hydrolytic activity, one at pH 7.5 and another at pH 9.5. 2. Phospholipid hydrolytic activity in microsomes from host liver and regenerating liver require Ca2+ for hydrolysis at pH 9.5, but not at pH 7.5. Hepatoma microsomes require Ca2+ for activity at both pH values. 3. Phospholipase A1 activity, stimulated by addition of Triton X-100 to the incubation mixtures, was detected in both host liver and regenerating liver microsomes. There was no evidence of phospholipase A1 activity in hepatoma microsomes. 4. Phospholipase A2 was detected in microsomes of all three tissues using 1-[1'-3H] hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamine as a substrate. The activity required calcium and was inhibited by Triton X-100. 5. Lysophospholipase activity was evident in the microsomes from all three tissues. The activity was inhibited by both Ca2+ and Triton X-100. 6. Differences were also detected between host liver and hepatoma microsomal phospholipid hydrolase activities with respect to the effect of increasing protein concentration, apparent Michaelis-Menten constants, and time course of the reaction.", "contents": "Properties of microsomal phospholipases in rat liver and hepatoma. Phospholipase A1, A2 and lysophospholipase activities in microsomes of Novikoff hepatoma host rat liver and regenerating rat liver were compared using 1-[9', 10'-3H2]palmitoyl-2-[1'-14C] linoleoyl-sn-glycero-3-phosphoethanolamine, 1-[1' -3H-]hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamine, and 1-[9', 10'-3H2]palmitoyl-sn-glycero-3-phosphoethanolamine as substrates. 1. Microsomes of all three tissues showed two pH dependent peaks of hydrolytic activity, one at pH 7.5 and another at pH 9.5. 2. Phospholipid hydrolytic activity in microsomes from host liver and regenerating liver require Ca2+ for hydrolysis at pH 9.5, but not at pH 7.5. Hepatoma microsomes require Ca2+ for activity at both pH values. 3. Phospholipase A1 activity, stimulated by addition of Triton X-100 to the incubation mixtures, was detected in both host liver and regenerating liver microsomes. There was no evidence of phospholipase A1 activity in hepatoma microsomes. 4. Phospholipase A2 was detected in microsomes of all three tissues using 1-[1'-3H] hexadecyl-2-acyl-sn-glycero-3-phosphoethanolamine as a substrate. The activity required calcium and was inhibited by Triton X-100. 5. Lysophospholipase activity was evident in the microsomes from all three tissues. The activity was inhibited by both Ca2+ and Triton X-100. 6. Differences were also detected between host liver and hepatoma microsomal phospholipid hydrolase activities with respect to the effect of increasing protein concentration, apparent Michaelis-Menten constants, and time course of the reaction."}
{"id": "PMID:10989", "title": "Purification and positional specificity of sn-glycerol-3-phosphate acyltransferase from Escherichia coli membranes.", "content": "SN-Glycerol-3-phosphate acyltransferase was solubilized from membranes of Escherichia coli B and K-12 and purified on an affinity column of Sepharose 4B coupled with 6-phosphogluconic acid. Phosphatidylglycerol was required for activation and stabilization of the purified enzyme. The acyl residues were exclusively transferred to the position 1 of sn-glycerol 3-phosphate by the enzyme, regardless of whether the acyl-CoA was saturated or unsaturated.", "contents": "Purification and positional specificity of sn-glycerol-3-phosphate acyltransferase from Escherichia coli membranes. SN-Glycerol-3-phosphate acyltransferase was solubilized from membranes of Escherichia coli B and K-12 and purified on an affinity column of Sepharose 4B coupled with 6-phosphogluconic acid. Phosphatidylglycerol was required for activation and stabilization of the purified enzyme. The acyl residues were exclusively transferred to the position 1 of sn-glycerol 3-phosphate by the enzyme, regardless of whether the acyl-CoA was saturated or unsaturated."}
{"id": "PMID:10990", "title": "Isolation and characterization of aldose reductase from calf brain.", "content": "Aldose reductase activity (alditol: NADP+ 1-oxidoreductase, EC 1.1.1.21) from calf brain was separated into two protein fractions by DEAE chromatography. Further purifcation by molecular sieve chromotography and electrofocusing yielding two distinctive enzymes, which were designated AR I and AR II. AR I was purified 646-fold and found to have an isoelectric point of 6.18. AR I was most active as a monomer with a molecular weight of 29 000 and appeared to be in equilibrium with a less active dimer. AR II was purified 425-fold and found to have an isoelectric point of 4.88. The molecular weight of this enzyme was 30 000. Although both enzymes had specificity for aldoses as substrates, AR I had two to three times larger turnover numbers with aromatic aldehydes and hexonates than did AR II. AR I was activated by sulfhydryl compounds and exhibited biphasic double reciprocal plots. AR I was more sensitive to inhibition by high substrate and phenobarbital concentrations than was AR II. AR I and AR II did not have antigenic similarity as tested by Ouchterlony immunodiffusion and counter immunoelectrophoresis. An immunochemical cross-reaction was observed  between AR II and lens aldose reductase.", "contents": "Isolation and characterization of aldose reductase from calf brain. Aldose reductase activity (alditol: NADP+ 1-oxidoreductase, EC 1.1.1.21) from calf brain was separated into two protein fractions by DEAE chromatography. Further purifcation by molecular sieve chromotography and electrofocusing yielding two distinctive enzymes, which were designated AR I and AR II. AR I was purified 646-fold and found to have an isoelectric point of 6.18. AR I was most active as a monomer with a molecular weight of 29 000 and appeared to be in equilibrium with a less active dimer. AR II was purified 425-fold and found to have an isoelectric point of 4.88. The molecular weight of this enzyme was 30 000. Although both enzymes had specificity for aldoses as substrates, AR I had two to three times larger turnover numbers with aromatic aldehydes and hexonates than did AR II. AR I was activated by sulfhydryl compounds and exhibited biphasic double reciprocal plots. AR I was more sensitive to inhibition by high substrate and phenobarbital concentrations than was AR II. AR I and AR II did not have antigenic similarity as tested by Ouchterlony immunodiffusion and counter immunoelectrophoresis. An immunochemical cross-reaction was observed  between AR II and lens aldose reductase."}
{"id": "PMID:10991", "title": "Studies on the role of methionine in porcine pancreatic phospholipase A2.", "content": "The unique methionine-15 residue located at the N-terminal site of iso- or beta-phospholipase A2 from porcine pancrease has been specifically carboxymethylated with iodoacetic acid. The modification results in a complete inactivation of the enzymatic activity toward micellar and monomeric substrates. Spectroscopic measurements reveled that the carboxymethylated protein still binds Ca2+ and monomeric substrates with comparable affinities as the native enzyeme. The active site histidine-54 residue in the modified enzyme shows a reactivity toward the active site-directed irreversible inhibitor p-bromophenacylbromide which is identical to that of the native enzyme. The alkylated protein, however, has lost its ability to bind to lipid-water interfaces. Although circular dichroic spectra of the carboxymethylated enzyme display some changes in the tertiary structure as compared with the native enzyme, the alpha-helix content remains rather constant. It is concluded that carboxymethylation of methionine-15 destroys the interface recognition site but has only limited influence on the active site of the molecule. Therefore, it seems that methionine-15 is not involved in the catalytic events but that this residue is part of the interface recognition site which embraces the N-terminal hydrophobic part of the enzyme: Ala-Leu-Trp-Gln-Phe-Arg-Ser-Met.", "contents": "Studies on the role of methionine in porcine pancreatic phospholipase A2. The unique methionine-15 residue located at the N-terminal site of iso- or beta-phospholipase A2 from porcine pancrease has been specifically carboxymethylated with iodoacetic acid. The modification results in a complete inactivation of the enzymatic activity toward micellar and monomeric substrates. Spectroscopic measurements reveled that the carboxymethylated protein still binds Ca2+ and monomeric substrates with comparable affinities as the native enzyeme. The active site histidine-54 residue in the modified enzyme shows a reactivity toward the active site-directed irreversible inhibitor p-bromophenacylbromide which is identical to that of the native enzyme. The alkylated protein, however, has lost its ability to bind to lipid-water interfaces. Although circular dichroic spectra of the carboxymethylated enzyme display some changes in the tertiary structure as compared with the native enzyme, the alpha-helix content remains rather constant. It is concluded that carboxymethylation of methionine-15 destroys the interface recognition site but has only limited influence on the active site of the molecule. Therefore, it seems that methionine-15 is not involved in the catalytic events but that this residue is part of the interface recognition site which embraces the N-terminal hydrophobic part of the enzyme: Ala-Leu-Trp-Gln-Phe-Arg-Ser-Met."}
{"id": "PMID:10992", "title": "The effect of calcium ions on the hydrolysis of benzoylarginine ethyl ester by porcine enteropeptidase.", "content": "Calcium ions are shown to have a marked pH-dependent effect on the kinetics of benzoyllarginine ethyl ester hydrolysis by porcine enteropeptidase (EC 3.4.21.9). Below pH 6.0, calcium ions stimulate benzoylarginine ethyl ester hydrolysis but inhibit this activity above pH 6.0. This effect is mainly on the Km for benzoylarginine ethyl ester. At pH 5.3, 2mM calcium ions reduce the Km for benzoylarginine ethyl ester from 0.31 mM to 0.26 mM while at pH 6.5 the Km increases four-fold from 0.035 mM to 0.12 mM in the presence of calcium ions. Enteropeptidase activity is not inhibited by ethylenediaminetetra-acetate indicating that calcium ions are a non-essential cofactor for benzoylarginine ethyl ester hydrolysis.", "contents": "The effect of calcium ions on the hydrolysis of benzoylarginine ethyl ester by porcine enteropeptidase. Calcium ions are shown to have a marked pH-dependent effect on the kinetics of benzoyllarginine ethyl ester hydrolysis by porcine enteropeptidase (EC 3.4.21.9). Below pH 6.0, calcium ions stimulate benzoylarginine ethyl ester hydrolysis but inhibit this activity above pH 6.0. This effect is mainly on the Km for benzoylarginine ethyl ester. At pH 5.3, 2mM calcium ions reduce the Km for benzoylarginine ethyl ester from 0.31 mM to 0.26 mM while at pH 6.5 the Km increases four-fold from 0.035 mM to 0.12 mM in the presence of calcium ions. Enteropeptidase activity is not inhibited by ethylenediaminetetra-acetate indicating that calcium ions are a non-essential cofactor for benzoylarginine ethyl ester hydrolysis."}
{"id": "PMID:10993", "title": "Purification and characterization of bile salt hydrolase from Bacteroides fragilis subsp. fragilis.", "content": "A high-molecular-weight (250 000) bile salt hydrolase (cholylglycine hydrolase, EC 3.5.-.-) was isolated and purified 128-fold from the \"spheroplast lysate\" fraction prepared from Bacteroids fragilis subsp. fragilis ATCC 25285. The intact enzyme had a molecular weight of approx. 250 000 as determined by gel infiltration chromatography. One major protein band, corresponding to a molecular weight of 32 500, was observed on 7% sodium dodecyl sulfate polyacrylamide gel electrophoresis of pooled fractions from DEAE-cellulose column chromatography (128-fold purified). The pH optimum for the 64-fold purified enzyme isolated from Bio-Gel A 1.5 M chromatography was 4.2 and bile salt hydrolase activity measured in intact cell suspensions had a pH optimum of 4.5. Substrate specificity studies indicated that taurine and glycine conjugates of cholic acid, chenodeoxycholic acid and deoxycholic acid were readily hydrolyzed; however, lithocholic acid conjugates were not hydrolyzed. Substrate saturation kinetics were biphasic with an intermediate plateau (0.2--0.3 mM) and a complete loss of enzymatic activity was observed at high concentration for certain substrates. The presence or absence of 7-alpha-hydroxysteroid dehydrogenase was absolutely correlated with that of bile salt hydrolase activity in six to ten strains and subspecies of B. fragilis.", "contents": "Purification and characterization of bile salt hydrolase from Bacteroides fragilis subsp. fragilis. A high-molecular-weight (250 000) bile salt hydrolase (cholylglycine hydrolase, EC 3.5.-.-) was isolated and purified 128-fold from the \"spheroplast lysate\" fraction prepared from Bacteroids fragilis subsp. fragilis ATCC 25285. The intact enzyme had a molecular weight of approx. 250 000 as determined by gel infiltration chromatography. One major protein band, corresponding to a molecular weight of 32 500, was observed on 7% sodium dodecyl sulfate polyacrylamide gel electrophoresis of pooled fractions from DEAE-cellulose column chromatography (128-fold purified). The pH optimum for the 64-fold purified enzyme isolated from Bio-Gel A 1.5 M chromatography was 4.2 and bile salt hydrolase activity measured in intact cell suspensions had a pH optimum of 4.5. Substrate specificity studies indicated that taurine and glycine conjugates of cholic acid, chenodeoxycholic acid and deoxycholic acid were readily hydrolyzed; however, lithocholic acid conjugates were not hydrolyzed. Substrate saturation kinetics were biphasic with an intermediate plateau (0.2--0.3 mM) and a complete loss of enzymatic activity was observed at high concentration for certain substrates. The presence or absence of 7-alpha-hydroxysteroid dehydrogenase was absolutely correlated with that of bile salt hydrolase activity in six to ten strains and subspecies of B. fragilis."}
{"id": "PMID:10994", "title": "On the partial reactivation of inactivated pantothenase from Pseudomonas fluorescens.", "content": "Partial reactivation of inactivated pantothenase (pantothenate amidohydrolase, EC 3.5.1.22) from Pseudomonas fluorescens was studied. After partial inactivation during storing, pantothenase activity is increased by 10-40% when incubated with, for instance, oxalate, oxaloacetate or pyruvate. Reactivation proceedes slowly; with oxaloacetate the stable level of enzyme activity is attained in 20-30 min. The same compounds also cause reactivation of thermally inactivated pantothenase when partial inactivation has occurred at 28-37 degrees C. The amount of the reactivating enzyme form is relatively greater the lower the temperature during inactivation, but it never exceeds 20% of the original amount of active enzyme. Also another, unstable form of pantothenase is formed in thermal inactivation. This form becomes inactivated in a few minutes after the heat treatment, at pH 6-8 and at temperatures between 0 and 10 degrees C. Reactivation causes special problems in enzyme kinetic measurements; for instance, curvature is found in the lines of Ki determination by the Dixon plot.", "contents": "On the partial reactivation of inactivated pantothenase from Pseudomonas fluorescens. Partial reactivation of inactivated pantothenase (pantothenate amidohydrolase, EC 3.5.1.22) from Pseudomonas fluorescens was studied. After partial inactivation during storing, pantothenase activity is increased by 10-40% when incubated with, for instance, oxalate, oxaloacetate or pyruvate. Reactivation proceedes slowly; with oxaloacetate the stable level of enzyme activity is attained in 20-30 min. The same compounds also cause reactivation of thermally inactivated pantothenase when partial inactivation has occurred at 28-37 degrees C. The amount of the reactivating enzyme form is relatively greater the lower the temperature during inactivation, but it never exceeds 20% of the original amount of active enzyme. Also another, unstable form of pantothenase is formed in thermal inactivation. This form becomes inactivated in a few minutes after the heat treatment, at pH 6-8 and at temperatures between 0 and 10 degrees C. Reactivation causes special problems in enzyme kinetic measurements; for instance, curvature is found in the lines of Ki determination by the Dixon plot."}
{"id": "PMID:10995", "title": "Studies on aspartase. III. Alteration of enzymatic properties upon trypsin-mediated activation.", "content": "Highly purified aspartase (L-aspartate ammonia-lyase, EC 4.3.1.1) from Escherichia coli, already of full activity, is further activated 3.3-fold by limited treatment with trypsin. The activation requires a few minutes to attain maximum level, and hereafter the activity gradually decreases to complete inactivation. Prior or intermediate addition of soybean trypsin inhibitor results in an immediate cessation of any further change in the enzyme activity. Upon trypsin-mediated activation no appreciable change is detected in the molecular weight of the enzyme subunits as judged from sodium dodecyl sulfate polyacrylamide gel electrophoresis, nor in the pH vs. activity profile in the presence of added metal ions. However, S0.5 and hill coefficient for L-aspartate considerably increase upon activation. As the trypsin-mediated activation proceeds, a marked absorbance difference spectrum of the trypsin-treated aspartase vs. untreated aspartase appears with negative absorbance maxima at 278 and 285 nm. When the trypsin-activated enzyme is denatured in 4 M guanidine-HCl, followed by removal of the denaturant by dilution, the enzyme activity is readily restored to as much as 1.5 times that of the native enzyme, indicating that the trypsin-activated enzyme is rather a stable molecule.", "contents": "Studies on aspartase. III. Alteration of enzymatic properties upon trypsin-mediated activation. Highly purified aspartase (L-aspartate ammonia-lyase, EC 4.3.1.1) from Escherichia coli, already of full activity, is further activated 3.3-fold by limited treatment with trypsin. The activation requires a few minutes to attain maximum level, and hereafter the activity gradually decreases to complete inactivation. Prior or intermediate addition of soybean trypsin inhibitor results in an immediate cessation of any further change in the enzyme activity. Upon trypsin-mediated activation no appreciable change is detected in the molecular weight of the enzyme subunits as judged from sodium dodecyl sulfate polyacrylamide gel electrophoresis, nor in the pH vs. activity profile in the presence of added metal ions. However, S0.5 and hill coefficient for L-aspartate considerably increase upon activation. As the trypsin-mediated activation proceeds, a marked absorbance difference spectrum of the trypsin-treated aspartase vs. untreated aspartase appears with negative absorbance maxima at 278 and 285 nm. When the trypsin-activated enzyme is denatured in 4 M guanidine-HCl, followed by removal of the denaturant by dilution, the enzyme activity is readily restored to as much as 1.5 times that of the native enzyme, indicating that the trypsin-activated enzyme is rather a stable molecule."}
{"id": "PMID:10996", "title": "Investigations on the kinetic properties of estrone glucuronyltransferase from pig kidney.", "content": "The microsomal fraction of the pig kidney catalyzes the glucuronidation of estrone in the presence of UDP-glucuronic acid. This bireactant system exhibits a sequential type of reaction mechanism. Increasing concentrations of either substrate increase the affinity of the enzyme for the other substrate. The Hill coefficient, n, was calculated to be 1.0 for both estrone and UDP-glucuronic acid. The Kestrone and KUDP-glucuronic acid are 6.6 muM and 254 muM, respectively. The estrone glucuronyltransferase (UDP-glucuronate: 17 beta-oestradiol 3-glucuronosyltransferase, EC 2.4.1.59) exhibits high substrate specificity in that it is inhibited noncompetetively by estradiol-17 beta, estradiol-17 alpha, estriol, testosterone, phenolphthalein and bilirubin; p-nitrophenol and o-aminophenol do not inhibit the glucuronidation of estrone. Mg2+ and Ca2+ were found to be nonessential activators. One of the two products of the reaction, estrone glucuronide, inhibits the enzyme competitively in the presence of increasing concentrations of UDP-glucuronic acid. The other product of the reaction, UDP, inhibits the enzyme noncompetitively with varying estrone concentrations and uncompetitively with varying UDP-glucuronic acid concentrations. Under incubation conditions for the glucuronidation of estrone, the enzyme catalyzes the reverse reaction with estrone glucuronide and UDP as reactants to an extent of about 0.4% of the forward reaction; this reverse reaction is also of a sequential type.", "contents": "Investigations on the kinetic properties of estrone glucuronyltransferase from pig kidney. The microsomal fraction of the pig kidney catalyzes the glucuronidation of estrone in the presence of UDP-glucuronic acid. This bireactant system exhibits a sequential type of reaction mechanism. Increasing concentrations of either substrate increase the affinity of the enzyme for the other substrate. The Hill coefficient, n, was calculated to be 1.0 for both estrone and UDP-glucuronic acid. The Kestrone and KUDP-glucuronic acid are 6.6 muM and 254 muM, respectively. The estrone glucuronyltransferase (UDP-glucuronate: 17 beta-oestradiol 3-glucuronosyltransferase, EC 2.4.1.59) exhibits high substrate specificity in that it is inhibited noncompetetively by estradiol-17 beta, estradiol-17 alpha, estriol, testosterone, phenolphthalein and bilirubin; p-nitrophenol and o-aminophenol do not inhibit the glucuronidation of estrone. Mg2+ and Ca2+ were found to be nonessential activators. One of the two products of the reaction, estrone glucuronide, inhibits the enzyme competitively in the presence of increasing concentrations of UDP-glucuronic acid. The other product of the reaction, UDP, inhibits the enzyme noncompetitively with varying estrone concentrations and uncompetitively with varying UDP-glucuronic acid concentrations. Under incubation conditions for the glucuronidation of estrone, the enzyme catalyzes the reverse reaction with estrone glucuronide and UDP as reactants to an extent of about 0.4% of the forward reaction; this reverse reaction is also of a sequential type."}
{"id": "PMID:10997", "title": "Interactions between phospholipids and barbiturates.", "content": "The effects of a number of barbiturates on the temperature of the lipid phase transition have been studied using chlorophyll a as a fluorescence probe. The barbiturates cause a reduction in the temperature of the phase transitions of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanolamine, the effects being greatest at lower pH values where more of the barbiturate is present in the uncharged form. There was no significant interaction between the barbiturates and dipalmitoyl phosphatidylserine. These and other observations on the actions of local anaesthetics are used to develop a model for local anaesthesia. It is suggested that the sodium channel is surrounded by an annulus of lipid in the gel state, this rigid microenvironment preventing the sodium channel relaxing from its active configuration to an inactive one. Local anaesthetics, which reduce the temperature of lipid phase transitions, trigger a change of the annular lipid from the gel to the liquid-crystalline state, with a consequent relaxation of the sodium channel to an inactive configuration, in which the sodium current is reduced or blocked.", "contents": "Interactions between phospholipids and barbiturates. The effects of a number of barbiturates on the temperature of the lipid phase transition have been studied using chlorophyll a as a fluorescence probe. The barbiturates cause a reduction in the temperature of the phase transitions of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanolamine, the effects being greatest at lower pH values where more of the barbiturate is present in the uncharged form. There was no significant interaction between the barbiturates and dipalmitoyl phosphatidylserine. These and other observations on the actions of local anaesthetics are used to develop a model for local anaesthesia. It is suggested that the sodium channel is surrounded by an annulus of lipid in the gel state, this rigid microenvironment preventing the sodium channel relaxing from its active configuration to an inactive one. Local anaesthetics, which reduce the temperature of lipid phase transitions, trigger a change of the annular lipid from the gel to the liquid-crystalline state, with a consequent relaxation of the sodium channel to an inactive configuration, in which the sodium current is reduced or blocked."}
{"id": "PMID:10998", "title": "Transport and phosphorylation of D-galactose in renal cortical cells.", "content": "An improved analytical procedure for the extraction and determination of total, free and phosphorylated tissue sugar is described. This method, employing ZnSO4 plus Ba(OH)2 for the precipitation of sugar phosphates, yields values identical with those obtained by the more laborious separation of free and phosphorylated sugar by ion-exchange chromatography. Erroneous values for free sugar due to the action of a Zn2+ -activated phosphatase and/or the lability to acids of some sugar phosphates, are avoided. Using this technique for the sudy of transport and phosphorylation of D-galactose in rabbit renal cortical slices and tissue extracts, it was found: 1. The cellular uptake of D-galactose was associated with the appearance of both free and phosphorylated sugar whether or not external Na+ was present. At 1 mM sugar, galactose was accumulated in the cells against a modest concentration gradient of 1.445 +/- 0.097 (n = 17). Galactose phosphate appeared in the cells considerably faster than free sugar under conditions of net uptake as well as of steady-state exchange (pulse-labelling). 2. Increasing saline pH (6-8) increased the cellular levels of sugar phosphate without affecting the steady-state values of free sugar. With tissue extracts, increasing pH also stimulated the activity of galactokinase and the dephosphorylation of galactose 1-phosphate by a Zn2+ -activated phosphatase. 3. 0.5 mM phlorizin inhibited the tissue uptake of galactose and its subsequent oxidation to CO2 only to a minor degree (30 and 10%, respectively). The absence of external Na+ further depressed the phlorizin effect. Preincubation of the tissue with phlorizin and subsequent washing in part abolished the inhibitory effect. The data suggest that a major portion of the galactose uptake by the tissue proceeds by a mechanism with a low affinity for phlorizin. 4. Efflux studies showed that the wash-out of free galactose from slices was associated with a net decrease of both free and phosphorylated tissue sugar. 5. The above results suggest the possibility that phosphorylation may represent a step in the Na+ -independent, phloretin-sensitive transfer of D-galactose across the antiluminal cell membrane. The participation of intracellular galactokinase and a Zn2+ -activated alkaline phosphatase in the maintenance of the steady state of free and phosphorylated galactose in the cells has been demonstrated.", "contents": "Transport and phosphorylation of D-galactose in renal cortical cells. An improved analytical procedure for the extraction and determination of total, free and phosphorylated tissue sugar is described. This method, employing ZnSO4 plus Ba(OH)2 for the precipitation of sugar phosphates, yields values identical with those obtained by the more laborious separation of free and phosphorylated sugar by ion-exchange chromatography. Erroneous values for free sugar due to the action of a Zn2+ -activated phosphatase and/or the lability to acids of some sugar phosphates, are avoided. Using this technique for the sudy of transport and phosphorylation of D-galactose in rabbit renal cortical slices and tissue extracts, it was found: 1. The cellular uptake of D-galactose was associated with the appearance of both free and phosphorylated sugar whether or not external Na+ was present. At 1 mM sugar, galactose was accumulated in the cells against a modest concentration gradient of 1.445 +/- 0.097 (n = 17). Galactose phosphate appeared in the cells considerably faster than free sugar under conditions of net uptake as well as of steady-state exchange (pulse-labelling). 2. Increasing saline pH (6-8) increased the cellular levels of sugar phosphate without affecting the steady-state values of free sugar. With tissue extracts, increasing pH also stimulated the activity of galactokinase and the dephosphorylation of galactose 1-phosphate by a Zn2+ -activated phosphatase. 3. 0.5 mM phlorizin inhibited the tissue uptake of galactose and its subsequent oxidation to CO2 only to a minor degree (30 and 10%, respectively). The absence of external Na+ further depressed the phlorizin effect. Preincubation of the tissue with phlorizin and subsequent washing in part abolished the inhibitory effect. The data suggest that a major portion of the galactose uptake by the tissue proceeds by a mechanism with a low affinity for phlorizin. 4. Efflux studies showed that the wash-out of free galactose from slices was associated with a net decrease of both free and phosphorylated tissue sugar. 5. The above results suggest the possibility that phosphorylation may represent a step in the Na+ -independent, phloretin-sensitive transfer of D-galactose across the antiluminal cell membrane. The participation of intracellular galactokinase and a Zn2+ -activated alkaline phosphatase in the maintenance of the steady state of free and phosphorylated galactose in the cells has been demonstrated."}
{"id": "PMID:10999", "title": "Transport and phosphorylation of 2-deoxy-D-galactase in renal cortical cells.", "content": "The transport and phosphorylation of 2-deoxy-D-[3H]galactose in rabbit renal cortical cells was studied. 1. The uptake of 2-deoxy-galactose by cortical slices is associated with an appearance of both free and phosphorylated sugar in the cells. At 1 mM external sugar the cells establish a steady-state gradient of free 2-deoxy-galactose of 3.97 +/- 0.15 (23 animals). 2. The acid-labile sugar phosphate accumulated in the tissue has been identified by a combination of paper and radio-chromatography, as well as on the basis of some of its chemical properties, as 2-deoxy-D-galactose 1-phosphate. Ice-cold trichloroacetic acid produces a decomposition of this compound. 3. Increasing external pH (6-8) brings about a decrease in the steady-state levels of both free and phosphorylated sugar in slices. On the other hand, increasing pH activates the phosphorylation of 2-deoxy-D-galactose by a crude kinase in a tissue extract. 4. Sugar phosphate accumulated in the cells is dephosphorylated by the action of a Zn2+ -activated phosphatase. 5. The efflux of 2-deoxy-D-galactose from the cells is rather slow compared with that found for D-galactose. The efflux is associated with some dephosphorylation of cellular sugar phosphate, and some loss of 2-deoxy-galactose phosphate into the wash-out medium takes place. 6. An inhibition analysis of the uptake of 2-deoxy-D-galactose by the slices indicates that the transport site is shared by D-galactose. The following points of interaction between the sugar molecule and the carrier are identified: C1-OH, C3-OH and C4-OH (both axial) and C6-OH. A (pyranose) ring structure is also essential. A close packing between the substrate and the carrier in the vicinity of C2 is indicated. 7. The data suggest that the above transport system is localized predominantly at the antiluminal (basolateral) face of the renal tubular cells. While the detailed mechanism of the actual transport step (i.e. active transport of the free sugar, or by the action of a phosphotransferase) is still unclear, the data present evidence that both galactokinase and a Zn2+ -activated phosphatase participate in the maintenance of an intracellular steady state of the transported sugar.", "contents": "Transport and phosphorylation of 2-deoxy-D-galactase in renal cortical cells. The transport and phosphorylation of 2-deoxy-D-[3H]galactose in rabbit renal cortical cells was studied. 1. The uptake of 2-deoxy-galactose by cortical slices is associated with an appearance of both free and phosphorylated sugar in the cells. At 1 mM external sugar the cells establish a steady-state gradient of free 2-deoxy-galactose of 3.97 +/- 0.15 (23 animals). 2. The acid-labile sugar phosphate accumulated in the tissue has been identified by a combination of paper and radio-chromatography, as well as on the basis of some of its chemical properties, as 2-deoxy-D-galactose 1-phosphate. Ice-cold trichloroacetic acid produces a decomposition of this compound. 3. Increasing external pH (6-8) brings about a decrease in the steady-state levels of both free and phosphorylated sugar in slices. On the other hand, increasing pH activates the phosphorylation of 2-deoxy-D-galactose by a crude kinase in a tissue extract. 4. Sugar phosphate accumulated in the cells is dephosphorylated by the action of a Zn2+ -activated phosphatase. 5. The efflux of 2-deoxy-D-galactose from the cells is rather slow compared with that found for D-galactose. The efflux is associated with some dephosphorylation of cellular sugar phosphate, and some loss of 2-deoxy-galactose phosphate into the wash-out medium takes place. 6. An inhibition analysis of the uptake of 2-deoxy-D-galactose by the slices indicates that the transport site is shared by D-galactose. The following points of interaction between the sugar molecule and the carrier are identified: C1-OH, C3-OH and C4-OH (both axial) and C6-OH. A (pyranose) ring structure is also essential. A close packing between the substrate and the carrier in the vicinity of C2 is indicated. 7. The data suggest that the above transport system is localized predominantly at the antiluminal (basolateral) face of the renal tubular cells. While the detailed mechanism of the actual transport step (i.e. active transport of the free sugar, or by the action of a phosphotransferase) is still unclear, the data present evidence that both galactokinase and a Zn2+ -activated phosphatase participate in the maintenance of an intracellular steady state of the transported sugar."}
{"id": "PMID:11000", "title": "Heterogeneity of histidine transport in the Ehrlich cell.", "content": "We have reexamined the heterogeneity shown by histidine in its uptake by the Ehrlich ascites tumor cell, in the face of a contradiction of our earlier interpretation. We again find the fraction of histidine uptake at neutral pH inhibitable by the model substrate for System A, 2-(methylamino)-isobutyric acid, to be fully dependent on the presence of Na+ or Li+. The small Na+ -independent component not attributable to System L can be identified with System Ly+ through its inhibitability by homoarginine. This component increases as the pH is lowered with an apparent pK' a of 6.1. The simultaneous decrease in the uptake by the neutral systems could be identified, for System L, with the same titration of histidine to its cationic form, but for System A the sharp decrease is identified with the protonation of a structure on the membrane rather than one on the substrate. The action of H+ in the latter case proved approximately non-competitive with Na+ when tested with ordinary substrates.", "contents": "Heterogeneity of histidine transport in the Ehrlich cell. We have reexamined the heterogeneity shown by histidine in its uptake by the Ehrlich ascites tumor cell, in the face of a contradiction of our earlier interpretation. We again find the fraction of histidine uptake at neutral pH inhibitable by the model substrate for System A, 2-(methylamino)-isobutyric acid, to be fully dependent on the presence of Na+ or Li+. The small Na+ -independent component not attributable to System L can be identified with System Ly+ through its inhibitability by homoarginine. This component increases as the pH is lowered with an apparent pK' a of 6.1. The simultaneous decrease in the uptake by the neutral systems could be identified, for System L, with the same titration of histidine to its cationic form, but for System A the sharp decrease is identified with the protonation of a structure on the membrane rather than one on the substrate. The action of H+ in the latter case proved approximately non-competitive with Na+ when tested with ordinary substrates."}
{"id": "PMID:11001", "title": "Calcium incorporation by smooth muscle microsomes.", "content": "The purpose of the present work was to study the factors influencing calcium incorporation into a microsomal fraction prepared from the longitudinal smooth muscle of the guinea-pig ileum. Calcium incorporation required the presence of both ATP and Mg2+ and was unaffected by azide. It was enhanced by oxalate; this effect was pH dependent and it was maximal at pH 6.6. The relation between calcium uptake with oxalate and free Ca2+ concentration in the medium was represented by a curve with an optimum for Ca2+ equal to 3-10-5 M. The threshold concentration was comprised between 5-10-7 and 10-6 7. The optimum calcium uptake rate was 4.5 nmol Ca2+/mg protein per min. In the absence of oxalate, two distinct groups of binding sites were identified. Low affinity sites had a binding constant of 7-104 M-1 and a maximum binding capacity of 0.6-106 M-1 and a binding capacity of 33 nmol Ca2+/mg protein; their capacity was sensitive to pH changes. In the absence of oxalate, Ca2+ binding was depressed by Na+ with respect to K+ or choline. When the medium was supplemented with oxalate, the stimulation of 45Ca incorporation was barely detectable in the presence of choline+ and it was lower in a medium containing Na+ instead of K+. The subcellular distribution profiles of calcium incorporation with and without oxalate indicate the microsomal location of both activities. However, the oxalate-stimulated calcium uptake activity sedimented faster than the calcium binding activity. The subcellular distribution of marker enzyme actvities has been examined. The present results indicate that Ca2+ incorporations with and without oxalate are the result of two processes likely related to two different structures. The role of microsomal calcium uptake in excitation-contraction coupling and its modification by the activity of the sodium pump is discussed.", "contents": "Calcium incorporation by smooth muscle microsomes. The purpose of the present work was to study the factors influencing calcium incorporation into a microsomal fraction prepared from the longitudinal smooth muscle of the guinea-pig ileum. Calcium incorporation required the presence of both ATP and Mg2+ and was unaffected by azide. It was enhanced by oxalate; this effect was pH dependent and it was maximal at pH 6.6. The relation between calcium uptake with oxalate and free Ca2+ concentration in the medium was represented by a curve with an optimum for Ca2+ equal to 3-10-5 M. The threshold concentration was comprised between 5-10-7 and 10-6 7. The optimum calcium uptake rate was 4.5 nmol Ca2+/mg protein per min. In the absence of oxalate, two distinct groups of binding sites were identified. Low affinity sites had a binding constant of 7-104 M-1 and a maximum binding capacity of 0.6-106 M-1 and a binding capacity of 33 nmol Ca2+/mg protein; their capacity was sensitive to pH changes. In the absence of oxalate, Ca2+ binding was depressed by Na+ with respect to K+ or choline. When the medium was supplemented with oxalate, the stimulation of 45Ca incorporation was barely detectable in the presence of choline+ and it was lower in a medium containing Na+ instead of K+. The subcellular distribution profiles of calcium incorporation with and without oxalate indicate the microsomal location of both activities. However, the oxalate-stimulated calcium uptake activity sedimented faster than the calcium binding activity. The subcellular distribution of marker enzyme actvities has been examined. The present results indicate that Ca2+ incorporations with and without oxalate are the result of two processes likely related to two different structures. The role of microsomal calcium uptake in excitation-contraction coupling and its modification by the activity of the sodium pump is discussed."}
{"id": "PMID:11003", "title": "Alternating current studies of charge carrier transport in lipid bilayers. Pentachlorophenol in lecithin-cholesterol membranes.", "content": "Surface and interior electrical properties of lecithin-cholesterol bilayer membranes treated with the uncoupler pentachlorophenol have been determined on the basis of a.c. measurements over a wide range of frequencies (0.02 to 1000 kHZ). The method used depends on accurately determining the resistance of the aqueous solution in series with each individual membrane by extrapolating admittance data into infinite frequency. Loss tangent vs. frequency curves are corrected by subtracting out a loss contribution which is present in untreated membranes and is due, presumably, to dielectric relaxation. The results, which are useful below 100 kHZ, can be fitted to loss tangent curves computed for a three-element equivalent circuit consisting of frequency independent conductance-capacitance pairs, arranged in series to represent surface and interior properties of membranes. Interior conductances agree with net conductances obtained from d.c. measurements. The pH and concentration dependence of surface conductance is consistent with a scheme of transport in which a fixed number of surface binding sites are filled preferentially with neutral pentachlorophenol molecules, which in turn dissociate to supply protons to the aqueous phase. Surface capacitances range from 15 to 90 times that of interior capacitance and show a systematic increase with pentachlorophenol concentration at high pH, and a decrease with concentration at low pH.", "contents": "Alternating current studies of charge carrier transport in lipid bilayers. Pentachlorophenol in lecithin-cholesterol membranes. Surface and interior electrical properties of lecithin-cholesterol bilayer membranes treated with the uncoupler pentachlorophenol have been determined on the basis of a.c. measurements over a wide range of frequencies (0.02 to 1000 kHZ). The method used depends on accurately determining the resistance of the aqueous solution in series with each individual membrane by extrapolating admittance data into infinite frequency. Loss tangent vs. frequency curves are corrected by subtracting out a loss contribution which is present in untreated membranes and is due, presumably, to dielectric relaxation. The results, which are useful below 100 kHZ, can be fitted to loss tangent curves computed for a three-element equivalent circuit consisting of frequency independent conductance-capacitance pairs, arranged in series to represent surface and interior properties of membranes. Interior conductances agree with net conductances obtained from d.c. measurements. The pH and concentration dependence of surface conductance is consistent with a scheme of transport in which a fixed number of surface binding sites are filled preferentially with neutral pentachlorophenol molecules, which in turn dissociate to supply protons to the aqueous phase. Surface capacitances range from 15 to 90 times that of interior capacitance and show a systematic increase with pentachlorophenol concentration at high pH, and a decrease with concentration at low pH."}
{"id": "PMID:11005", "title": "The lasat mouse: a new model for transplantation of human tissues.", "content": "A new animal model characterized by hereditary athymia and asplenia was developed by breeding congenitally athymic with hereditarily asplenic mice. The new hybrids have no cellular immunity and produce significantly less antibody than nude mice. The lasat mouse has been found useful for the transplantation of normal and malignant hemopoietic cells and other neoplastic tissues of human origin.", "contents": "The lasat mouse: a new model for transplantation of human tissues. A new animal model characterized by hereditary athymia and asplenia was developed by breeding congenitally athymic with hereditarily asplenic mice. The new hybrids have no cellular immunity and produce significantly less antibody than nude mice. The lasat mouse has been found useful for the transplantation of normal and malignant hemopoietic cells and other neoplastic tissues of human origin."}
{"id": "PMID:11006", "title": "The processing of human bone marrow for cryopreservation and reinfusion.", "content": "Bone marrow was aspirated from 22 patients with solid tumors. A median of 1.2 x 10(10) net bone marrow cells were obtained during a 1 hour 45 minute operative procedure. Three methods were used to concentrate the bone marrow for cryopreservation. The greatest concentration of mononuclear cells was obtained by the Haemonetics pheresis procedure. Bone marrow was cryopreserved in 10 % DMSO in volumes ranging from 150 to 700 ml. The thawed marrow was further processed to remove both DMSO and free hemoglobin prior to reinfusion. Cell clumping was observed in the first 6 of the 10 marrows thawed. Acidification of the thawed marrow to pH 6.65 was found to retard cell clumping. The immediate recovery of cells frozen was 66 % with a viability of 50 %. The mean number of viable mononuclear bone marrow cells per kilogram available for reinfusion was therefore 5.5 x 10(7).", "contents": "The processing of human bone marrow for cryopreservation and reinfusion. Bone marrow was aspirated from 22 patients with solid tumors. A median of 1.2 x 10(10) net bone marrow cells were obtained during a 1 hour 45 minute operative procedure. Three methods were used to concentrate the bone marrow for cryopreservation. The greatest concentration of mononuclear cells was obtained by the Haemonetics pheresis procedure. Bone marrow was cryopreserved in 10 % DMSO in volumes ranging from 150 to 700 ml. The thawed marrow was further processed to remove both DMSO and free hemoglobin prior to reinfusion. Cell clumping was observed in the first 6 of the 10 marrows thawed. Acidification of the thawed marrow to pH 6.65 was found to retard cell clumping. The immediate recovery of cells frozen was 66 % with a viability of 50 %. The mean number of viable mononuclear bone marrow cells per kilogram available for reinfusion was therefore 5.5 x 10(7)."}
{"id": "PMID:11007", "title": "Physical characteristics of porous cellulose beads as supporting material for immobilized enzymes.", "content": "Cellulose beads prepared in this report have high porosity (75-80%) and evenly distributed pores. The pore size is about 1000 A. The cellulose beads are physically strong and contain large amounts of reactive groups, making them suitable for use as carriers for immobilized enzymes.", "contents": "Physical characteristics of porous cellulose beads as supporting material for immobilized enzymes. Cellulose beads prepared in this report have high porosity (75-80%) and evenly distributed pores. The pore size is about 1000 A. The cellulose beads are physically strong and contain large amounts of reactive groups, making them suitable for use as carriers for immobilized enzymes."}
{"id": "PMID:11010", "title": "[Induction of tyrosine aminotransferase by blastomogenic metabolites of tryptophan and tyrosine].", "content": "A comparitive study was made of the effect produced by endogenous blastomogenic agents (3-oxyanthranylic and paraoxphenyl-lactic acids) and their nonblastomogenic anaogues (anthranylic and phenyl-lactic acids) on the activity of tyrosine-aminotranspherase in the rat liver. Blastomogenic metabolites proved to be capable of inducing sharply the enzyme activity. This phenomenon and data on the role played by the increase in the activity of tyrosine-aminotranspherase and tryptophane-oxygenase in tyrosine and tryptophane catabolism on the way of a possible formation of blastomogenic metabolites permitted to put forward a suggestion on the \"chain reaction\" of accumulation of the endogenous blastomogenic agents in the organism.", "contents": "[Induction of tyrosine aminotransferase by blastomogenic metabolites of tryptophan and tyrosine]. A comparitive study was made of the effect produced by endogenous blastomogenic agents (3-oxyanthranylic and paraoxphenyl-lactic acids) and their nonblastomogenic anaogues (anthranylic and phenyl-lactic acids) on the activity of tyrosine-aminotranspherase in the rat liver. Blastomogenic metabolites proved to be capable of inducing sharply the enzyme activity. This phenomenon and data on the role played by the increase in the activity of tyrosine-aminotranspherase and tryptophane-oxygenase in tyrosine and tryptophane catabolism on the way of a possible formation of blastomogenic metabolites permitted to put forward a suggestion on the \"chain reaction\" of accumulation of the endogenous blastomogenic agents in the organism."}
{"id": "PMID:11011", "title": "[Effect of cocaine on the tyrosine hydroxylase of rat hypothalamus].", "content": "The influence of cocaine on tyrosine hydroxilase of rat brain hypothalamus was investigated in vivo (0.5 mg/kg) and in vitro (10(--6)--10(--5)M). Cocaine was used as a substance with a known adrenergic type of action. It was shown that under standard conditions cocaine in vitro increased the enzyme activity and decreased the Km for DMPH4 cofactor without changing Vmax of the reaction analyzed by the membrane enzyme. Cocaine in vitro decreased the tyrosine hydroxylase activity, especially that of the membrane enzyme. In this case there occurred a decrease of Km for DMPH4 and a decrease of Vmax of the reaction. The decrease of Vmax is considered to be the result of the secondary effect of cocaine.", "contents": "[Effect of cocaine on the tyrosine hydroxylase of rat hypothalamus]. The influence of cocaine on tyrosine hydroxilase of rat brain hypothalamus was investigated in vivo (0.5 mg/kg) and in vitro (10(--6)--10(--5)M). Cocaine was used as a substance with a known adrenergic type of action. It was shown that under standard conditions cocaine in vitro increased the enzyme activity and decreased the Km for DMPH4 cofactor without changing Vmax of the reaction analyzed by the membrane enzyme. Cocaine in vitro decreased the tyrosine hydroxylase activity, especially that of the membrane enzyme. In this case there occurred a decrease of Km for DMPH4 and a decrease of Vmax of the reaction. The decrease of Vmax is considered to be the result of the secondary effect of cocaine."}
{"id": "PMID:11012", "title": "[Analysis of the structure of the components of the convulsive action of corazole following administration of sulazepam and its metabolites to mice].", "content": "A study was made of the interrelationship between the minimal effective doses of pseudoclonic and clonico-tonic convulsions, and also tonic extension caused by the intravenous injection of corazol to mice and the effect of anticonvulsive action of sulazepam and its metabolites (diazepam, desmethyldiazepam and oxadiazepam) on this process. It was shown that all the compounds under study increased the values of the minimal effective doses by the recorded indices of the convulsive seizure, whereas the maximum of the anticonvulsive activity was reached 15 minutes after the sulazepam and oxazepam, and 5 to 30 min after diazepam administration. There proved to be a distinct correlation between the minimal effective doses values of the recorded indices of the confulsive seizure in the control animals which also persisted after the administration of the agents under study. It is supposed that sulazepam and its metabolites increased the minimal effective doses of corazol for the recorded effects, but failed to alter the general picture of the convulsive attack and did not influence the dispersion corazol dose-effect dependence.", "contents": "[Analysis of the structure of the components of the convulsive action of corazole following administration of sulazepam and its metabolites to mice]. A study was made of the interrelationship between the minimal effective doses of pseudoclonic and clonico-tonic convulsions, and also tonic extension caused by the intravenous injection of corazol to mice and the effect of anticonvulsive action of sulazepam and its metabolites (diazepam, desmethyldiazepam and oxadiazepam) on this process. It was shown that all the compounds under study increased the values of the minimal effective doses by the recorded indices of the convulsive seizure, whereas the maximum of the anticonvulsive activity was reached 15 minutes after the sulazepam and oxazepam, and 5 to 30 min after diazepam administration. There proved to be a distinct correlation between the minimal effective doses values of the recorded indices of the confulsive seizure in the control animals which also persisted after the administration of the agents under study. It is supposed that sulazepam and its metabolites increased the minimal effective doses of corazol for the recorded effects, but failed to alter the general picture of the convulsive attack and did not influence the dispersion corazol dose-effect dependence."}
{"id": "PMID:11013", "title": "[Participation of phytohemagglutinin-transformed mouse lymphocytes in development of the \"graft-versus-host\" reaction].", "content": "Transformed lymphocytes obtained as a result of phytohemagglutinin-stimulation of the cells of the lymph nodes of the CBA mice were incapable of realizing the graft-versus-host reaction in administration to the sublethally irradiated (CBAXC57BL/6) F1 hybrids. In this case the graft-versus-host reaction is induced by small untransformed lymphocytes with the same concentration of surface antigens detected by the antilymphocytic serum as in the intact lymphocytes.", "contents": "[Participation of phytohemagglutinin-transformed mouse lymphocytes in development of the \"graft-versus-host\" reaction]. Transformed lymphocytes obtained as a result of phytohemagglutinin-stimulation of the cells of the lymph nodes of the CBA mice were incapable of realizing the graft-versus-host reaction in administration to the sublethally irradiated (CBAXC57BL/6) F1 hybrids. In this case the graft-versus-host reaction is induced by small untransformed lymphocytes with the same concentration of surface antigens detected by the antilymphocytic serum as in the intact lymphocytes."}
{"id": "PMID:11014", "title": "[Suppression of interferon synthesis during the \"graft-versus-host\" reaction in F1(CBAXC57BL/6) mice].", "content": "The development of the graft-versus-host reaction (GVHR) in the F1(1CBA X C57BL/6 hybrid mice after the transplantation of spleen cells from the C57BL/6 parent donor resulted in a strong inhibition of the serum interferon production induced by the intraperitoneal injection of the Newcastle disease virus. In vitro with the mouse bone marrow cells during the development of the GVHR the interferon response was first reduced and then disappeared completely. The described phenomenon could therefore serve as an index of the development of the GVHR.", "contents": "[Suppression of interferon synthesis during the \"graft-versus-host\" reaction in F1(CBAXC57BL/6) mice]. The development of the graft-versus-host reaction (GVHR) in the F1(1CBA X C57BL/6 hybrid mice after the transplantation of spleen cells from the C57BL/6 parent donor resulted in a strong inhibition of the serum interferon production induced by the intraperitoneal injection of the Newcastle disease virus. In vitro with the mouse bone marrow cells during the development of the GVHR the interferon response was first reduced and then disappeared completely. The described phenomenon could therefore serve as an index of the development of the GVHR."}
{"id": "PMID:11018", "title": "Analgesia produced by morphine when acting from the liquor space.", "content": "1 In cats analgesia was produced by morphine sulphate introduced into different parts of the liquor space in doses too small to be effective on intravenous injection. Analgesia was measured with the tail pinch method of Russell & Tate (1975). 2 On infusion into the fourth ventricle or into the subarachnoid space beneath the ventral surface of the brain stem caudal to the pons, doses of 100 to 200 mug of morphine sulphate were sufficient to produce strong long-lasting analgesia. On injection into the cisterna magna somewhat larger doses (400 to 800mug) were required. 3 It is concluded that the site where morphine acts when producing analgesia in all three circumstances is at the ventral surface of the brain stem. 4 The possibility is discussed that the structures acted upon are tryptaminergic nerve fibres. They arise from the raphe nuclei, belong to a descending inhibitory pathway, and on their way to the spinal cord, reach the ventral surface of the brain stem lateral to each pyramid, where they could be reached and acted upon by the morphine. This theory postulates a morphine sensitivity of tryptaminergic nerve fibres.", "contents": "Analgesia produced by morphine when acting from the liquor space. 1 In cats analgesia was produced by morphine sulphate introduced into different parts of the liquor space in doses too small to be effective on intravenous injection. Analgesia was measured with the tail pinch method of Russell & Tate (1975). 2 On infusion into the fourth ventricle or into the subarachnoid space beneath the ventral surface of the brain stem caudal to the pons, doses of 100 to 200 mug of morphine sulphate were sufficient to produce strong long-lasting analgesia. On injection into the cisterna magna somewhat larger doses (400 to 800mug) were required. 3 It is concluded that the site where morphine acts when producing analgesia in all three circumstances is at the ventral surface of the brain stem. 4 The possibility is discussed that the structures acted upon are tryptaminergic nerve fibres. They arise from the raphe nuclei, belong to a descending inhibitory pathway, and on their way to the spinal cord, reach the ventral surface of the brain stem lateral to each pyramid, where they could be reached and acted upon by the morphine. This theory postulates a morphine sensitivity of tryptaminergic nerve fibres."}
{"id": "PMID:11027", "title": "Behavioural treatment of orgasmic dysfunction: a controlled study.", "content": "Twenty-two anorgasmic women received 20 sessions of a multiple-technique behavioural therapy. The design included blind ratings by two independent assessors, multiple assessment instruments, and a waiting list control group. Treatment was significantly better than no treatment in terms of: (1) the percentage of patients experiencing orgasm during at least 50 per cent of sexual relations; (2) the percentage of women reporting satisfactory sexual relations at least 50 per cent of the time; (3) patients' ratings of positive reactions to various sexual behaviours; and (4) assessors' global clinical ratings. Significant improvement was also noted on the MMPI, IPAT, and Symptom Check List. Improvement was maintained at a follow-up average 9 months later. These results support the impression that a behavioural approach offers much promise in treating female orgasmic dysfunction.", "contents": "Behavioural treatment of orgasmic dysfunction: a controlled study. Twenty-two anorgasmic women received 20 sessions of a multiple-technique behavioural therapy. The design included blind ratings by two independent assessors, multiple assessment instruments, and a waiting list control group. Treatment was significantly better than no treatment in terms of: (1) the percentage of patients experiencing orgasm during at least 50 per cent of sexual relations; (2) the percentage of women reporting satisfactory sexual relations at least 50 per cent of the time; (3) patients' ratings of positive reactions to various sexual behaviours; and (4) assessors' global clinical ratings. Significant improvement was also noted on the MMPI, IPAT, and Symptom Check List. Improvement was maintained at a follow-up average 9 months later. These results support the impression that a behavioural approach offers much promise in treating female orgasmic dysfunction."}
{"id": "PMID:11029", "title": "The relationship of the serum gastrin and calcium concentrations in patients with multiple endocrine neoplasia type I.", "content": "The relationship between the serum gastrin and calcium concentrations has been examined in patients with multiple endocrine neoplasia type I. Variations in gastrin concentrations were induced by metiamide and secretin; calcium concentrations were altered by parathyroidectomy and by calcium infusion. Changes in the serum gastrin concentrations were not accompanied by changes in the serum calcium concentration. However, alteration of the serum calcium was accompanied by significant parallel changes in the serum gastrin. It is concluded that acute changes in the serum calcium may induce changes in the serum gastrin. Parathyroidectomy in these patients produced a fall in the serum gastrin, but the ability to produce large quantities of gastrin remains. It is postulated that the thyro-parathyroid hormones may modulate the relationship between calcium and gastrin.", "contents": "The relationship of the serum gastrin and calcium concentrations in patients with multiple endocrine neoplasia type I. The relationship between the serum gastrin and calcium concentrations has been examined in patients with multiple endocrine neoplasia type I. Variations in gastrin concentrations were induced by metiamide and secretin; calcium concentrations were altered by parathyroidectomy and by calcium infusion. Changes in the serum gastrin concentrations were not accompanied by changes in the serum calcium concentration. However, alteration of the serum calcium was accompanied by significant parallel changes in the serum gastrin. It is concluded that acute changes in the serum calcium may induce changes in the serum gastrin. Parathyroidectomy in these patients produced a fall in the serum gastrin, but the ability to produce large quantities of gastrin remains. It is postulated that the thyro-parathyroid hormones may modulate the relationship between calcium and gastrin."}
{"id": "PMID:11030", "title": "Inhibitors of gastric secretion: current progress.", "content": "Several new compounds have become available recently which are potent inhibitors of gastric secretion. The therapeutic potential of these inhibitors in the peptic ulcer diathesis is reviewed and it is concluded that the histamine H2-receptor antagonists show most promise at present. The prostaglandins and gastro-intestinal polypeptides are of considerable physiological interest but are unlikely to have clinical importance in the immediate future.", "contents": "Inhibitors of gastric secretion: current progress. Several new compounds have become available recently which are potent inhibitors of gastric secretion. The therapeutic potential of these inhibitors in the peptic ulcer diathesis is reviewed and it is concluded that the histamine H2-receptor antagonists show most promise at present. The prostaglandins and gastro-intestinal polypeptides are of considerable physiological interest but are unlikely to have clinical importance in the immediate future."}
{"id": "PMID:11035", "title": "Effect of surgical isolation of the hypothalamus on its neurotransmitter content.", "content": "The concentrations of norepinephrine, dopamine-beta-hydroxylase, dopamine, tyrosine hydroxylase, phenylethanolamine-N-methyltransferase, serotonin, tryptophan hydroxylase, histamine, glutamic acid decarboxylase, and choline acetyltransferase were determined in selected hypothalamic nuclei and in the median eminence after deafferentation of the medial basal hypothalamus. Norepinephrine and dopamine-beta-hydroxylase fell markedly while dopamine and tyrosine hydroxylase did not. Serotonin also decreased in all regions studied; histamine decreased in none. Choline acetyltransferase, phenylethanolamine-N-methyltransferase, and glutamic acid decarboxylase declined in some areas, but not in others.", "contents": "Effect of surgical isolation of the hypothalamus on its neurotransmitter content. The concentrations of norepinephrine, dopamine-beta-hydroxylase, dopamine, tyrosine hydroxylase, phenylethanolamine-N-methyltransferase, serotonin, tryptophan hydroxylase, histamine, glutamic acid decarboxylase, and choline acetyltransferase were determined in selected hypothalamic nuclei and in the median eminence after deafferentation of the medial basal hypothalamus. Norepinephrine and dopamine-beta-hydroxylase fell markedly while dopamine and tyrosine hydroxylase did not. Serotonin also decreased in all regions studied; histamine decreased in none. Choline acetyltransferase, phenylethanolamine-N-methyltransferase, and glutamic acid decarboxylase declined in some areas, but not in others."}
{"id": "PMID:11038", "title": "Cardiac responsiveness to beta-adrenergic stimulation in experimental anemia.", "content": "Cardiac reactivity of beta-adrenergic stimulation was assessed by isoproterenol dose-reponse curves (dose range 0.025-0.4 mug/kg) before and 1 h after the rapid induction of anemia in dogs anesthetized with halothane:N2O:O2. Anemai (hematocrit = 16 +/- 4%) was induced by an isovolumic exchange transfusion with Dextran 70, and was followed by significant increments in cardiac output (+57 +/- 9%), max dP/dt of the left ventricle (+37 +/- 7%), and in peak acceleration of blood flow in the ascending aorta (+46 +/- 13%). Anemia was associated with a significant reduction of the chronotropic responses to all but the lowest dose of isoproterenol. The simultaneously determined inotropic responses (max dP/dt) where the same before and after the induction of anemia. The responses in terms of peak acceleration of aortic blood flow tended to be greater in the anemic than in the control phase, at all dose levels used. These findings indicate that in rapidly induced experimental anemia the heart is capable of responding to marked degrees of beta-adrenergic stimulation, representing a more than two-fold increase in the dP/dt.", "contents": "Cardiac responsiveness to beta-adrenergic stimulation in experimental anemia. Cardiac reactivity of beta-adrenergic stimulation was assessed by isoproterenol dose-reponse curves (dose range 0.025-0.4 mug/kg) before and 1 h after the rapid induction of anemia in dogs anesthetized with halothane:N2O:O2. Anemai (hematocrit = 16 +/- 4%) was induced by an isovolumic exchange transfusion with Dextran 70, and was followed by significant increments in cardiac output (+57 +/- 9%), max dP/dt of the left ventricle (+37 +/- 7%), and in peak acceleration of blood flow in the ascending aorta (+46 +/- 13%). Anemia was associated with a significant reduction of the chronotropic responses to all but the lowest dose of isoproterenol. The simultaneously determined inotropic responses (max dP/dt) where the same before and after the induction of anemia. The responses in terms of peak acceleration of aortic blood flow tended to be greater in the anemic than in the control phase, at all dose levels used. These findings indicate that in rapidly induced experimental anemia the heart is capable of responding to marked degrees of beta-adrenergic stimulation, representing a more than two-fold increase in the dP/dt."}
{"id": "PMID:11039", "title": "Propranolol induces acute natriuresis by beta blockade and dopaminergic stimulation.", "content": "dl-Propranolol (0.8-1.6 mg/kg - h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin-angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by beta blockade and requires post ganglionic nerve function but is independent of alpha receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal beta blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking beta receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.", "contents": "Propranolol induces acute natriuresis by beta blockade and dopaminergic stimulation. dl-Propranolol (0.8-1.6 mg/kg - h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin-angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by beta blockade and requires post ganglionic nerve function but is independent of alpha receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal beta blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking beta receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation."}
{"id": "PMID:11040", "title": "Differences in the altered energy metabolism of hemorrhagic shock and hypoxemia.", "content": "The effect of hemorrhagic shock, hypoxemia, and anoxia on the levels of adenine and pyridine nucleotides of liver and kidney was assessed. ATP levels in liver and kidney of animals in shock or animals subjected to 7 min of anoxia decreased by 85 and 73%, respectively. Under hypoxic conditions (arterial PO2 AT 18 MMHg), the decrease was only 62 and 48% in liver and kidney, respectively. Tissue NAD levels decreased and NADH levels increased during shock but were found to be essentially unaltered during experimental hypoxemia. Thus, shock produced greater alterations in adenine and pyridine nucleotides than did hypoxemia alone, indicating that stagnant hypoxemia due to shock is more deleterious to energy metabolism than is severe hypoxemia with an otherwise normal circulation. The results also suggest that if an anterial PO2 OF 18 MMHg represents the initial stages of tissue hypoxia, then tissue ATP levels are a more sensitive indicator of this than NAD levels.", "contents": "Differences in the altered energy metabolism of hemorrhagic shock and hypoxemia. The effect of hemorrhagic shock, hypoxemia, and anoxia on the levels of adenine and pyridine nucleotides of liver and kidney was assessed. ATP levels in liver and kidney of animals in shock or animals subjected to 7 min of anoxia decreased by 85 and 73%, respectively. Under hypoxic conditions (arterial PO2 AT 18 MMHg), the decrease was only 62 and 48% in liver and kidney, respectively. Tissue NAD levels decreased and NADH levels increased during shock but were found to be essentially unaltered during experimental hypoxemia. Thus, shock produced greater alterations in adenine and pyridine nucleotides than did hypoxemia alone, indicating that stagnant hypoxemia due to shock is more deleterious to energy metabolism than is severe hypoxemia with an otherwise normal circulation. The results also suggest that if an anterial PO2 OF 18 MMHg represents the initial stages of tissue hypoxia, then tissue ATP levels are a more sensitive indicator of this than NAD levels."}
{"id": "PMID:11041", "title": "Reduction in brain tyrosine hydroxylase activity following acetylcholinesterase blockade in rats.", "content": "Activation of cholinergic neurons in the brain is produced by administration of the acetylcholinesterase inhibitors physostigmine and diisopropylfluorophosphate (DFP). This activation has a biphasic effect on tyrosine hydroxylase (EC 4.14.3-) activity. The acute effect of DFP, 1 mg/kg, intraperitoneally, or physostigmine, 0.2 mg/kg, intravenously, or 10 mug, intraventricularly, was a rapid reduction in tyrosine hydroxylase activity in the hypothalamus. The activities of DOPA decarboxylase (EC 4.1.1.28) and dopamine-beta-hydroxylase (EC 1.14.17.1) were not changed. In contrast to the acute effect, chronic administration of physostigmine, 0.2 mg/kg, intravenously, twice daily for 7 days produced an increase in tyrosine hydroxylase activity in the hypothalamus. The rapid acute effects may be due to an allosteric inactivation of tyrosine hydroxylase, while the chronic effects may reflect enzyme induction.", "contents": "Reduction in brain tyrosine hydroxylase activity following acetylcholinesterase blockade in rats. Activation of cholinergic neurons in the brain is produced by administration of the acetylcholinesterase inhibitors physostigmine and diisopropylfluorophosphate (DFP). This activation has a biphasic effect on tyrosine hydroxylase (EC 4.14.3-) activity. The acute effect of DFP, 1 mg/kg, intraperitoneally, or physostigmine, 0.2 mg/kg, intravenously, or 10 mug, intraventricularly, was a rapid reduction in tyrosine hydroxylase activity in the hypothalamus. The activities of DOPA decarboxylase (EC 4.1.1.28) and dopamine-beta-hydroxylase (EC 1.14.17.1) were not changed. In contrast to the acute effect, chronic administration of physostigmine, 0.2 mg/kg, intravenously, twice daily for 7 days produced an increase in tyrosine hydroxylase activity in the hypothalamus. The rapid acute effects may be due to an allosteric inactivation of tyrosine hydroxylase, while the chronic effects may reflect enzyme induction."}
{"id": "PMID:11042", "title": "Reduced hemoglobin affinity for oxygen in venous blood following hemodilution, independent of changes in pH or PCO2.", "content": "A rapidly induced and readily reversible shift in the affinity of hemoglobin for oxygen has been demonstrated. The shift, similar to the Bohr effect, is independent of PCO2 or pH changes. It occurred within 30 min of hemodilution and was seen in portal venous blood but not arterial blood. A hypothesis is suggested involving a phasic alteration in levels of 2,3-diphosphoglycerate (DPG) or ATP binding to hemoglobin. It is proposed that, following hemodilution, the degree of these phosphates to hemoglobin increases on passage through the intestinal vascular bed. The increased DPG binding to hemoglobin results in displacement of additional oxygen. As the blood becomes reoxygenated, the levels of DPG-hemoglobin binding decline and DPG is displaced from the hemoglobin by oxygen.", "contents": "Reduced hemoglobin affinity for oxygen in venous blood following hemodilution, independent of changes in pH or PCO2. A rapidly induced and readily reversible shift in the affinity of hemoglobin for oxygen has been demonstrated. The shift, similar to the Bohr effect, is independent of PCO2 or pH changes. It occurred within 30 min of hemodilution and was seen in portal venous blood but not arterial blood. A hypothesis is suggested involving a phasic alteration in levels of 2,3-diphosphoglycerate (DPG) or ATP binding to hemoglobin. It is proposed that, following hemodilution, the degree of these phosphates to hemoglobin increases on passage through the intestinal vascular bed. The increased DPG binding to hemoglobin results in displacement of additional oxygen. As the blood becomes reoxygenated, the levels of DPG-hemoglobin binding decline and DPG is displaced from the hemoglobin by oxygen."}
{"id": "PMID:11043", "title": "Microdose mammography.", "content": "Tens of thousands of mammograms are performed daily in the United States. Accumulated radiation biologic data suggest that approximately 90-rad is the level of radition to the breast above which the incidence of cancer may be increase. A microdose system of roentgenography is described that provides better images at one-third to one-fifth the exposure of the commonly used low-dose system and about one-eight to one-tenth the dose of Xeromammography. This system should allow for repeated x-ray study in a patient as required, without exceeding the critical level.", "contents": "Microdose mammography. Tens of thousands of mammograms are performed daily in the United States. Accumulated radiation biologic data suggest that approximately 90-rad is the level of radition to the breast above which the incidence of cancer may be increase. A microdose system of roentgenography is described that provides better images at one-third to one-fifth the exposure of the commonly used low-dose system and about one-eight to one-tenth the dose of Xeromammography. This system should allow for repeated x-ray study in a patient as required, without exceeding the critical level."}
{"id": "PMID:11049", "title": "An ESR study of the anchoring of spin-labeled stearic acid in lecithin multilayers.", "content": "In egg lecithin-water lamellar phases, spin-labeled stearic acid gives two superimposed ESR spectra which are only well resolved when the temperature is greater than 30 degrees C. These two spectral components are attributed to the dissociated and non-dissociated forms of the fatty acid carboxylic group, anchored at two different positions in the polar interface constituted by the hydrated lipid polar heads. Results on such interactions of other functional groups (spin-labeled fatty ester and fatty alcohol) are also presented.", "contents": "An ESR study of the anchoring of spin-labeled stearic acid in lecithin multilayers. In egg lecithin-water lamellar phases, spin-labeled stearic acid gives two superimposed ESR spectra which are only well resolved when the temperature is greater than 30 degrees C. These two spectral components are attributed to the dissociated and non-dissociated forms of the fatty acid carboxylic group, anchored at two different positions in the polar interface constituted by the hydrated lipid polar heads. Results on such interactions of other functional groups (spin-labeled fatty ester and fatty alcohol) are also presented."}
{"id": "PMID:11051", "title": "[Guinea pig liver cytosol has an L-threonine deaminase activity distinct from L-serine deaminase].", "content": "Using sodium sulfate precipitation, \"Sephadex G200\" gel filtration and polyacrylamide gel electrophoresis, a L-threonine desaminase was demonstrated in the Guinea-Pig liver cytosol. This enzyme was separated from the guinea pig liver L-serine desaminase possessing an auxiliary activity on L-threonine substrate described by us in a previous work. The optimals for pH (7,1) and temperature (+ 55 degrees C) and the apparent molecular weight (134,000 + 20,000) were established.", "contents": "[Guinea pig liver cytosol has an L-threonine deaminase activity distinct from L-serine deaminase]. Using sodium sulfate precipitation, \"Sephadex G200\" gel filtration and polyacrylamide gel electrophoresis, a L-threonine desaminase was demonstrated in the Guinea-Pig liver cytosol. This enzyme was separated from the guinea pig liver L-serine desaminase possessing an auxiliary activity on L-threonine substrate described by us in a previous work. The optimals for pH (7,1) and temperature (+ 55 degrees C) and the apparent molecular weight (134,000 + 20,000) were established."}
{"id": "PMID:11052", "title": "Comparison of internal mammary artery and saphenous vein bypass grafts for myocardial revascularization: exercise test and angiographic correlations.", "content": "The effectiveness of myocardial perfusion with internal mammary artery (IMA) bypass revascularization has been questioned. We compared 37 patients with single patent IMA bypass grafts with 26 patients who had single patent saphenous vein graft (SVG) bypass. Serial computer assisted graded maximal stress testing was used for quantitation of palliation. Patients were classified and compared according to the completeness of revascularization by postoperative catheterization. All patient subgroups, had statistically significant improvements in work capacity, maximal heart rate, maximal rate-pressure products, abnormal exercise electrocardiograms, and exercise-induced angina pectoris. The quantitative improvements in these measurements of patient palliation were the same during postoperative stress tests after either SVG or IMA revascularization. Considering the overall higher patency rate of the IMA bypass, the data indicate that this procedure, when surgically applicable, is preferable to SVG bypass.", "contents": "Comparison of internal mammary artery and saphenous vein bypass grafts for myocardial revascularization: exercise test and angiographic correlations. The effectiveness of myocardial perfusion with internal mammary artery (IMA) bypass revascularization has been questioned. We compared 37 patients with single patent IMA bypass grafts with 26 patients who had single patent saphenous vein graft (SVG) bypass. Serial computer assisted graded maximal stress testing was used for quantitation of palliation. Patients were classified and compared according to the completeness of revascularization by postoperative catheterization. All patient subgroups, had statistically significant improvements in work capacity, maximal heart rate, maximal rate-pressure products, abnormal exercise electrocardiograms, and exercise-induced angina pectoris. The quantitative improvements in these measurements of patient palliation were the same during postoperative stress tests after either SVG or IMA revascularization. Considering the overall higher patency rate of the IMA bypass, the data indicate that this procedure, when surgically applicable, is preferable to SVG bypass."}
{"id": "PMID:11053", "title": "Renal acidification in hypothyroid man.", "content": "The role of thyroid hormone in renal hydrogen ion secretion remains largely unknown, and there is only limited information on renal acidification in hypothyroid patients. In the present study two of five adult male patients with untreated primary hypothyroidism and without clinical evidence of systemic autoimmune disease were unable to lower their urine pH appropriately after short duration acid-loading. Since, prior to acid-loading, their arterial blood gas values were within the normal range and urinary bicarbonate excretion was trival, the findings are consistent with the incomplete syndrome of distal renal tubular acidosis. Although the mechanism of this abnormality remains unknown, thyroxine deficiency per se may in part be responsible.", "contents": "Renal acidification in hypothyroid man. The role of thyroid hormone in renal hydrogen ion secretion remains largely unknown, and there is only limited information on renal acidification in hypothyroid patients. In the present study two of five adult male patients with untreated primary hypothyroidism and without clinical evidence of systemic autoimmune disease were unable to lower their urine pH appropriately after short duration acid-loading. Since, prior to acid-loading, their arterial blood gas values were within the normal range and urinary bicarbonate excretion was trival, the findings are consistent with the incomplete syndrome of distal renal tubular acidosis. Although the mechanism of this abnormality remains unknown, thyroxine deficiency per se may in part be responsible."}
{"id": "PMID:11056", "title": "Group desensitization of dissimilar anxieties.", "content": "Group desensitization is an effective, efficient anxiety-reduction therapy that, nonetheless, is not applicable in most mental health settings. This paper outlines several procedural modifications that make possible the desensitization of diverse anxieties within a single group and thus make group desensitization a more practical strategy.", "contents": "Group desensitization of dissimilar anxieties. Group desensitization is an effective, efficient anxiety-reduction therapy that, nonetheless, is not applicable in most mental health settings. This paper outlines several procedural modifications that make possible the desensitization of diverse anxieties within a single group and thus make group desensitization a more practical strategy."}
{"id": "PMID:11078", "title": "Effect of ascorbic acid on arylsulfatase A and B activities in human chondrocyte cultures.", "content": "Cultured normal human articular cartilage chondrocytes exhibited decreasing levels of arylsulfatase A and B activities when grown in the presence of increasing levels of ascorbic acid (0 to 90 mug/ml) in the media. That this was not a general effect on all lysosomal enzymes was supported by the increase in acid phosphatase activity and no change in beta-glucuronidase activity observed with increasing levels of vitamin C under identical culture conditions. No decrease in either arylsulfatase activity was observed when ascorbic acid was replaced by ascorbate-2-sulfate. Ascorbic acid did not inhibit either arylsulfatase activity when added directly to the assay mixture. These data, combined with results of mixing experiments, suggest that the effect of vitamin C is mediated through cellular factors produced in response to its inclusion in the growth media.", "contents": "Effect of ascorbic acid on arylsulfatase A and B activities in human chondrocyte cultures. Cultured normal human articular cartilage chondrocytes exhibited decreasing levels of arylsulfatase A and B activities when grown in the presence of increasing levels of ascorbic acid (0 to 90 mug/ml) in the media. That this was not a general effect on all lysosomal enzymes was supported by the increase in acid phosphatase activity and no change in beta-glucuronidase activity observed with increasing levels of vitamin C under identical culture conditions. No decrease in either arylsulfatase activity was observed when ascorbic acid was replaced by ascorbate-2-sulfate. Ascorbic acid did not inhibit either arylsulfatase activity when added directly to the assay mixture. These data, combined with results of mixing experiments, suggest that the effect of vitamin C is mediated through cellular factors produced in response to its inclusion in the growth media."}
{"id": "PMID:11079", "title": "Enzymes from human articular cartilage: isolation of arylsulfatase B and its comparison with arylsulfatase A.", "content": "This study describes the isolation of arylsulfatases A and B (arylsulfate sulfohydrolase EC 3.1.6.1) from human articular cartilage. These enzymes were extracted from collagenase digests of tissue homogenates. After fractionation with ammonium sulfate the enzymes were separated from each other by DEAE-cellulose chromatography and further purified by gel filtration on Sephadex G-200. Sulfatase B, subsequently chromatographed on CM-cellulose was apparently homogenous as judged by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. The enzyme has a pH optimum of 5.6, a molecular weight of 51,000 and Km of 2.6 mM for 4-nitrocatechol sulfate. Sulfatase A was found to be a glycoprotein with a pH optimum of 4.8, a molecular weight of 105,000 and a Km of 0.16 mM for 4-nitrocatechol sulfate. The competitive inhibition of both enzymes by inorganic sulfate, sulfite and phosphate support the likelihood of a common reaction mechanism. In contrast to sulfatase B which showed minimal inhibition, sulfatase A was totally inhibited by 5 mM N-ethylmaleimide.", "contents": "Enzymes from human articular cartilage: isolation of arylsulfatase B and its comparison with arylsulfatase A. This study describes the isolation of arylsulfatases A and B (arylsulfate sulfohydrolase EC 3.1.6.1) from human articular cartilage. These enzymes were extracted from collagenase digests of tissue homogenates. After fractionation with ammonium sulfate the enzymes were separated from each other by DEAE-cellulose chromatography and further purified by gel filtration on Sephadex G-200. Sulfatase B, subsequently chromatographed on CM-cellulose was apparently homogenous as judged by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. The enzyme has a pH optimum of 5.6, a molecular weight of 51,000 and Km of 2.6 mM for 4-nitrocatechol sulfate. Sulfatase A was found to be a glycoprotein with a pH optimum of 4.8, a molecular weight of 105,000 and a Km of 0.16 mM for 4-nitrocatechol sulfate. The competitive inhibition of both enzymes by inorganic sulfate, sulfite and phosphate support the likelihood of a common reaction mechanism. In contrast to sulfatase B which showed minimal inhibition, sulfatase A was totally inhibited by 5 mM N-ethylmaleimide."}
{"id": "PMID:11080", "title": "Lorazepam as a sedative-amnesic in an intensive care unit.", "content": "A clinical study was carried out to evaluate the usefulness of intravenous lorazepam, given for sedation instead of opiate narcotics or diazepam, in 25 seriously-ill patients being treated in a respiratory and intensive care unit. All but 3 patients were on assisted ventilation. Standard doses of 4 mg lorazepam were given at 4 or 6-hourly intervals for periods up to 25 days. ECG, haemodynamic stability and biological determinations were monitored constantly. Apart from some delay in onset of action, lorazepam proved to be a useful sedative with diminished recall on the part of the patients. No side-effects were reported, nor was there any local reaction to the injection. Cardiac output was measured in 9 patients following intravenous administration of a single-dose of either 4 mg or 8 mg lorazepam. No significant changes were recorded.", "contents": "Lorazepam as a sedative-amnesic in an intensive care unit. A clinical study was carried out to evaluate the usefulness of intravenous lorazepam, given for sedation instead of opiate narcotics or diazepam, in 25 seriously-ill patients being treated in a respiratory and intensive care unit. All but 3 patients were on assisted ventilation. Standard doses of 4 mg lorazepam were given at 4 or 6-hourly intervals for periods up to 25 days. ECG, haemodynamic stability and biological determinations were monitored constantly. Apart from some delay in onset of action, lorazepam proved to be a useful sedative with diminished recall on the part of the patients. No side-effects were reported, nor was there any local reaction to the injection. Cardiac output was measured in 9 patients following intravenous administration of a single-dose of either 4 mg or 8 mg lorazepam. No significant changes were recorded."}
{"id": "PMID:11086", "title": "[Effective treatment of duodenal ulcer with cimetidine (author's transl)].", "content": "Twelve male duodenal ulcer in-patients received in a double-blind trial either the histamine H2-receptor antagonist cimetidine (4 X 200 mg/d p.o.) or placebo capsules. Ulcer sizes were assessed endoscopically before therapy followed by repeat endoscopy at weekly intervals. Duodenal ulcer healing was significantly more rapid in cimetidine-treated patients than in those receiving the placebo (chi2 test; P less than 0.0005). Plotting of log ulcer sizes (mm2) against time (days) resulted in regression lines the slopes of which indicated the respective half-time of ulcer healing: about 6 days on cimetidine therapy and about 20 days on placebo treatment. Gastric secretion of acid, protein, pepsin, and N-acetylneuraminic acid-containing glycoproteins was not altered by a 4-week course of daily cimetidine or placebo, nor pancreatic secretion of bicarbonate and enzymes. No statistically significant changes in laboratory findings (haemoglobin, white blood-cells, neutrophils, platelets, alkaline phosphatase, blood-urea, serum-creatinine, GOT, GPT) were associated with treatment.", "contents": "[Effective treatment of duodenal ulcer with cimetidine (author's transl)]. Twelve male duodenal ulcer in-patients received in a double-blind trial either the histamine H2-receptor antagonist cimetidine (4 X 200 mg/d p.o.) or placebo capsules. Ulcer sizes were assessed endoscopically before therapy followed by repeat endoscopy at weekly intervals. Duodenal ulcer healing was significantly more rapid in cimetidine-treated patients than in those receiving the placebo (chi2 test; P less than 0.0005). Plotting of log ulcer sizes (mm2) against time (days) resulted in regression lines the slopes of which indicated the respective half-time of ulcer healing: about 6 days on cimetidine therapy and about 20 days on placebo treatment. Gastric secretion of acid, protein, pepsin, and N-acetylneuraminic acid-containing glycoproteins was not altered by a 4-week course of daily cimetidine or placebo, nor pancreatic secretion of bicarbonate and enzymes. No statistically significant changes in laboratory findings (haemoglobin, white blood-cells, neutrophils, platelets, alkaline phosphatase, blood-urea, serum-creatinine, GOT, GPT) were associated with treatment."}
{"id": "PMID:11087", "title": "[Treatment of diabetic coma and precoma with continuous low-dose insulin infusions (author's transl)].", "content": "13 patients, nine women and four men, aged 22 to 83 years, were treated for diabetic coma or precoma between September 1974 and January 1976. Ten patients were known diabetics and six of them had been treated with insulin. On admission blood sugar was 32.4 +/- 3.3 mmol/l (5.84 +/- 0.6 g/l). The capillary blood pH was 7.15 +/- 0.06 (n = 13). Treatment consisted of continuous insulin infusion (6 IU soluble insulin/hour), physiological saline, potassium substitution and sodium bicarbonate (if the pH was below 7.15). In the first hours of treatment 98 +/- 12IU of insulin, 6.5 +/- 0.5 litres of fluid, 168 +/- 22 mmol of potassium and 237 +/- 55 mmol NaHCO3 were required. During the first 4 hours of the insulin infusion the blood sugar decrease per hour was 3.55 mmol/l (0.64 g/l). Hypokalaemia during treatment occurred in one case, hypoglycaemia was not observed. A preceding treatment with insulin and severe acidosis did not influence therapeutic success. Twelve patients were treated successfully, one patient died 6 hours after admission following mesenteric arterial embolism.", "contents": "[Treatment of diabetic coma and precoma with continuous low-dose insulin infusions (author's transl)]. 13 patients, nine women and four men, aged 22 to 83 years, were treated for diabetic coma or precoma between September 1974 and January 1976. Ten patients were known diabetics and six of them had been treated with insulin. On admission blood sugar was 32.4 +/- 3.3 mmol/l (5.84 +/- 0.6 g/l). The capillary blood pH was 7.15 +/- 0.06 (n = 13). Treatment consisted of continuous insulin infusion (6 IU soluble insulin/hour), physiological saline, potassium substitution and sodium bicarbonate (if the pH was below 7.15). In the first hours of treatment 98 +/- 12IU of insulin, 6.5 +/- 0.5 litres of fluid, 168 +/- 22 mmol of potassium and 237 +/- 55 mmol NaHCO3 were required. During the first 4 hours of the insulin infusion the blood sugar decrease per hour was 3.55 mmol/l (0.64 g/l). Hypokalaemia during treatment occurred in one case, hypoglycaemia was not observed. A preceding treatment with insulin and severe acidosis did not influence therapeutic success. Twelve patients were treated successfully, one patient died 6 hours after admission following mesenteric arterial embolism."}
{"id": "PMID:11091", "title": "[Tranquilizers. Pharmacologic aspects].", "content": "An inventory was made of the various substances utilized as minor tranquillizers in man. Throughout the various methods of study of these drugs in animals the main pharmacological properties of tranquillizing drugs were considered. Attention is drawn on the various secondary or adverse effects of minor tranquillizers.", "contents": "[Tranquilizers. Pharmacologic aspects]. An inventory was made of the various substances utilized as minor tranquillizers in man. Throughout the various methods of study of these drugs in animals the main pharmacological properties of tranquillizing drugs were considered. Attention is drawn on the various secondary or adverse effects of minor tranquillizers."}
{"id": "PMID:11092", "title": "[The sector and the walls of the asylum].", "content": "The author has been able to strengthen his position of self confident, active practitioner by means of a noteworthy case: patient suffering of a chronic delusion whose internement has been avoided by the prescription of a long acting drug.", "contents": "[The sector and the walls of the asylum]. The author has been able to strengthen his position of self confident, active practitioner by means of a noteworthy case: patient suffering of a chronic delusion whose internement has been avoided by the prescription of a long acting drug."}
{"id": "PMID:11093", "title": "Interaction of uteroglobin with progesterone, 5alphapregnane-3,20-dione and estrogens.", "content": "Uteroglobin was obtained from 5 day pregnant rabbits and purified to homogeneity by Sephadex G 75 and DEAE-cellulose chromatographies. Progesterone binding to uteroglobin was decreased by lyophilization and enhanced by SH-reducing agents. Dithiothreitol was more effective than dithioerythritol, and beta-mercaptoethanol was only active at 25 to 100 mM concentrations. SH-blocking agents (iodoacetate, iodoacetamide, phydroxymercuribenzoate and, dithiobisnitrobenzoic acid) inhibited binding. In the absence of SH-reducing agents only one in every 500 uteroglobin molecules bound the hormone, whereas under optimal conditions (20 mM dithiothreitol) one in every two molecules bound progesterone. There was no significant difference in equilibrium dissociation constants under these two conditions. Uteroglobin had a relatively high affinity for progesterone (KD=4.1 X 10(-7)M) but a threefold higher affinity for 5alpha-pregnane-3,20-dione (KD=1.3 X 10(-7)M). Estradiol was bound but non-specifically with a very low affinity, and its binding was not enhanced by SH-reducing agents. Hormonal specificity of binding to uteroglobin was different from that of binding to rabbit uterine progesterone receptor. Various synthetic progestagens (chlormadinone acetate, norethisterone, R5020) were bound to the latter but not to the former protein. Diethylstilbestrol had some affinity (15% of that of progesterone) for uteroglobin and no affinity for the progesterone receptor. Uteroglobin incubated in the presence or absence of cofactors (NADH and NADPH) with or without dithiothreitol did not metabolize progesterone.", "contents": "Interaction of uteroglobin with progesterone, 5alphapregnane-3,20-dione and estrogens. Uteroglobin was obtained from 5 day pregnant rabbits and purified to homogeneity by Sephadex G 75 and DEAE-cellulose chromatographies. Progesterone binding to uteroglobin was decreased by lyophilization and enhanced by SH-reducing agents. Dithiothreitol was more effective than dithioerythritol, and beta-mercaptoethanol was only active at 25 to 100 mM concentrations. SH-blocking agents (iodoacetate, iodoacetamide, phydroxymercuribenzoate and, dithiobisnitrobenzoic acid) inhibited binding. In the absence of SH-reducing agents only one in every 500 uteroglobin molecules bound the hormone, whereas under optimal conditions (20 mM dithiothreitol) one in every two molecules bound progesterone. There was no significant difference in equilibrium dissociation constants under these two conditions. Uteroglobin had a relatively high affinity for progesterone (KD=4.1 X 10(-7)M) but a threefold higher affinity for 5alpha-pregnane-3,20-dione (KD=1.3 X 10(-7)M). Estradiol was bound but non-specifically with a very low affinity, and its binding was not enhanced by SH-reducing agents. Hormonal specificity of binding to uteroglobin was different from that of binding to rabbit uterine progesterone receptor. Various synthetic progestagens (chlormadinone acetate, norethisterone, R5020) were bound to the latter but not to the former protein. Diethylstilbestrol had some affinity (15% of that of progesterone) for uteroglobin and no affinity for the progesterone receptor. Uteroglobin incubated in the presence or absence of cofactors (NADH and NADPH) with or without dithiothreitol did not metabolize progesterone."}
{"id": "PMID:11094", "title": "Progesterone metabolism in vitro by rabbit testes at different stages of development.", "content": "Testicular homogenates from white rabbits of 0.4, 1, 3, 4, 5, 8, 18, and 24 months of age were incubated with [3H]progesterone and NADPH. At 12 days of age, major C21-17-OH-and C19- steroids formed from progesterone were 17alpha-hydroxyprogesterone and testosterone. However, at 4-24 months of age, 17alpha-hydroxyprogesterone, 3beta,17alpha-dihydroxy-5alpha-pregnan-20-one, and 5alpha-reduced C19-steroids such as 17beta-hydroxy-5alpha-androstan-3-one, 3beta-hydroxy-5alpha-androstan-17-one, and 5alpha-androstane-3beta,17beta-diol were the major products. The formation of significant quantities of 5alpha-reduced C19-steroids, which had been demonstrated previously only in prepubertal testes of rats and mice, was present in prepubertal as well as adult testes of rabbits. These findings clearly indicate that the metabolic patterns of progesterone in the adult rabbit differ from those in the adult rat and mouse. The major C19-steroids formed by testes are testosterone in the adult rat and mouse, but 5alpha-reduced C19-steroids in the adult rabbit.", "contents": "Progesterone metabolism in vitro by rabbit testes at different stages of development. Testicular homogenates from white rabbits of 0.4, 1, 3, 4, 5, 8, 18, and 24 months of age were incubated with [3H]progesterone and NADPH. At 12 days of age, major C21-17-OH-and C19- steroids formed from progesterone were 17alpha-hydroxyprogesterone and testosterone. However, at 4-24 months of age, 17alpha-hydroxyprogesterone, 3beta,17alpha-dihydroxy-5alpha-pregnan-20-one, and 5alpha-reduced C19-steroids such as 17beta-hydroxy-5alpha-androstan-3-one, 3beta-hydroxy-5alpha-androstan-17-one, and 5alpha-androstane-3beta,17beta-diol were the major products. The formation of significant quantities of 5alpha-reduced C19-steroids, which had been demonstrated previously only in prepubertal testes of rats and mice, was present in prepubertal as well as adult testes of rabbits. These findings clearly indicate that the metabolic patterns of progesterone in the adult rabbit differ from those in the adult rat and mouse. The major C19-steroids formed by testes are testosterone in the adult rat and mouse, but 5alpha-reduced C19-steroids in the adult rabbit."}
{"id": "PMID:11095", "title": "Direct determination of ligand interactions with beta-adrenergic receptors on intact turkey erythrocytes: correlation of binding with biological activity.", "content": "Previous studies on the interaction of labeled beta-adrenergic blockers with beta-adrenergic receptors have employed broken cell or membrane preparations. We have now carried out direct binding analysis on intact turkey erythrocytes employing the potent, high specific activity blocker [125I]-hydroxbenzylpindolol (HYP). [125I]HYP binds to a single class of receptor sites with a K of 5.3 X 10(10)M-1 and a binding capacity of 400-500 sites/cell. These results as well as the kinetics of association and dissociation and lack of evidence for negative cooperativity all agree well with studies reported earlier on membrane preparations from the same cells. True dissociation constants (Kd) for agonists and antagonists determined by inhibition of binding of [125I]HYP are in good agreement with results in membrane preparations. These Kd's have been compared directly with activation or inhibition constants for effects on adenylate cyclase using generation of [14C]cAMP from [14C]adenine in intact cells. The close correlation between effects on binding and adenylate cyclase activity in whole cells are similar to results obtained in membrane preparations in the presence of guanine nucleotides, suggesting the presence of an analogous regulatory substance in vivo.", "contents": "Direct determination of ligand interactions with beta-adrenergic receptors on intact turkey erythrocytes: correlation of binding with biological activity. Previous studies on the interaction of labeled beta-adrenergic blockers with beta-adrenergic receptors have employed broken cell or membrane preparations. We have now carried out direct binding analysis on intact turkey erythrocytes employing the potent, high specific activity blocker [125I]-hydroxbenzylpindolol (HYP). [125I]HYP binds to a single class of receptor sites with a K of 5.3 X 10(10)M-1 and a binding capacity of 400-500 sites/cell. These results as well as the kinetics of association and dissociation and lack of evidence for negative cooperativity all agree well with studies reported earlier on membrane preparations from the same cells. True dissociation constants (Kd) for agonists and antagonists determined by inhibition of binding of [125I]HYP are in good agreement with results in membrane preparations. These Kd's have been compared directly with activation or inhibition constants for effects on adenylate cyclase using generation of [14C]cAMP from [14C]adenine in intact cells. The close correlation between effects on binding and adenylate cyclase activity in whole cells are similar to results obtained in membrane preparations in the presence of guanine nucleotides, suggesting the presence of an analogous regulatory substance in vivo."}
{"id": "PMID:11096", "title": "The fate of ACTH released from rat anterior pituitary into the incubation medium in vitro: enzymatic degradation and acid activation.", "content": "The bioactivity of ACTH released from isolated rat anterior pituitary glands into the incubation medium was determined. After the pituitaries were removed, ACTH activity in the medium decreased exponentially during further incubation at 37degreesC. The loss of ACTH activity was temperature- and pH-dependent and inhibited both by protease inhibitor (trasylol) and by preheating. Crude tissue extracts from median eminence, cerebral cortex and liver similarly inhibited the loss of ACTH activity. These results indicate that ACTH released into the medium may be destroyed by proteolytic enzyme(s) from the rat anterior pituitary. ACTH activity in the incubation medium was increased promptly by acidification of the medium to pH 1.5-2.5 with HC1, and reduced to the initial level by NaOH reneutralization of the medium (pH 6.8-7.8). These phenomena were not observed after the incubation medium had been heated at 100degreesC for 5 min.", "contents": "The fate of ACTH released from rat anterior pituitary into the incubation medium in vitro: enzymatic degradation and acid activation. The bioactivity of ACTH released from isolated rat anterior pituitary glands into the incubation medium was determined. After the pituitaries were removed, ACTH activity in the medium decreased exponentially during further incubation at 37degreesC. The loss of ACTH activity was temperature- and pH-dependent and inhibited both by protease inhibitor (trasylol) and by preheating. Crude tissue extracts from median eminence, cerebral cortex and liver similarly inhibited the loss of ACTH activity. These results indicate that ACTH released into the medium may be destroyed by proteolytic enzyme(s) from the rat anterior pituitary. ACTH activity in the incubation medium was increased promptly by acidification of the medium to pH 1.5-2.5 with HC1, and reduced to the initial level by NaOH reneutralization of the medium (pH 6.8-7.8). These phenomena were not observed after the incubation medium had been heated at 100degreesC for 5 min."}
{"id": "PMID:11097", "title": "Ferredoxin from a red alga, Porphyra umbilicalis.", "content": "A plant-algal type ferredoxin was isolated from the red alga, Porphyra umbilicalis. In its oxidised form the ferredoxin had absorption maxima at 277, (281), 323, 420 and 462 nm. Two atoms each of non-haem iron and labile sulphur were present per molecule protein. The midpoint potential of the protein was -400 mV and it effectively mediated electron transport in the NADP-photoreduction system of barley. The amino acid composition of Porphyra umbilicalis ferredoxin was determined as (Lys4, His2, Arg1, Asx10, Thr8, Ser7, Glx16-17, Pro3, Gly7, Ala8, Cys5, Val6, Met1, Ile5, Leu8, Tyr5, Phe2). The minimum molecular weight of approximately 11000 was confirmed by sedimentation-equilibrium studies in the analytical ultracentrifuge. Approaching half of the total amino acid sequence was determined by means of an automatic sequencer.", "contents": "Ferredoxin from a red alga, Porphyra umbilicalis. A plant-algal type ferredoxin was isolated from the red alga, Porphyra umbilicalis. In its oxidised form the ferredoxin had absorption maxima at 277, (281), 323, 420 and 462 nm. Two atoms each of non-haem iron and labile sulphur were present per molecule protein. The midpoint potential of the protein was -400 mV and it effectively mediated electron transport in the NADP-photoreduction system of barley. The amino acid composition of Porphyra umbilicalis ferredoxin was determined as (Lys4, His2, Arg1, Asx10, Thr8, Ser7, Glx16-17, Pro3, Gly7, Ala8, Cys5, Val6, Met1, Ile5, Leu8, Tyr5, Phe2). The minimum molecular weight of approximately 11000 was confirmed by sedimentation-equilibrium studies in the analytical ultracentrifuge. Approaching half of the total amino acid sequence was determined by means of an automatic sequencer."}
{"id": "PMID:11098", "title": "The antigen-inexperienced thymic suppressor cells: a class of lymphocytes in the young chicken thymus that inhibits antibody production and cell-mediated immune responses.", "content": "Transfer of thymus cells from young chickens in combination with a light whole body irradiation (360 R) was found to suppress the rejection of skin grafts across strong histocompatibility (B) differences. On the average, the suppressed animals also showed decreased serum hemagglutinin titers against erythrocytes of the skin donor strain and a decreased graft-versus-host (GvH) reactivity against embryos of this strain. The thymic suppressor cells can be obtained from animals that have not experienced the antigen under test. However, after transfer and contact to the antigen (skin graft) they can lead to the formation of specific (\"activated\") suppressor cells and can mediate in the long run a specific inhibition of the response to this antigen. The suppressive activity is associated with a bursa-dependent cellular subpopulation in the thymus that is different from B lymphocytes, B precursor cells or GvH-reactive T cells. The bursa dependency of the thymic suppressor cell suggests that functionally different lineages of thymic and thymus-derived lymphocytes are derived from different sources of prethymic stem cells. The suppressor cells are predominantly found in the young chicken thymus and already detectable in the 16-day-old embryo, while poor suppressive activity is found in the adult thymus. The suppressive effect can be obtained with thymus cells from either syngeneic or allogeneic donors. Embryonic allogeneic donors provide suppressive cell preparations free of GvH reactivity. The possibility that the thymus suppressor cells mediate self tolerance and \"neonatal tolerance\" is discussed.", "contents": "The antigen-inexperienced thymic suppressor cells: a class of lymphocytes in the young chicken thymus that inhibits antibody production and cell-mediated immune responses. Transfer of thymus cells from young chickens in combination with a light whole body irradiation (360 R) was found to suppress the rejection of skin grafts across strong histocompatibility (B) differences. On the average, the suppressed animals also showed decreased serum hemagglutinin titers against erythrocytes of the skin donor strain and a decreased graft-versus-host (GvH) reactivity against embryos of this strain. The thymic suppressor cells can be obtained from animals that have not experienced the antigen under test. However, after transfer and contact to the antigen (skin graft) they can lead to the formation of specific (\"activated\") suppressor cells and can mediate in the long run a specific inhibition of the response to this antigen. The suppressive activity is associated with a bursa-dependent cellular subpopulation in the thymus that is different from B lymphocytes, B precursor cells or GvH-reactive T cells. The bursa dependency of the thymic suppressor cell suggests that functionally different lineages of thymic and thymus-derived lymphocytes are derived from different sources of prethymic stem cells. The suppressor cells are predominantly found in the young chicken thymus and already detectable in the 16-day-old embryo, while poor suppressive activity is found in the adult thymus. The suppressive effect can be obtained with thymus cells from either syngeneic or allogeneic donors. Embryonic allogeneic donors provide suppressive cell preparations free of GvH reactivity. The possibility that the thymus suppressor cells mediate self tolerance and \"neonatal tolerance\" is discussed."}
{"id": "PMID:11099", "title": "Inhibition of T cell activity in vivo: a test model for quantitative evaluation.", "content": "A test model is presented which, in comparison with the conventional models of skin transplantation or graft-versus-host (GvH) reaction in mice, permits a more sensitive quantitative evaluation of T cell inhibition in vivo. Prospective donors (type AA) are immunized with prospective recipient material (type AB); the resulting T cell reaction of A versus B is inhibited by consecutive treatment. Extent of inhibition can be evaluated after transfer of the pretreated AA material onto AB recipients by calculation of remaining GvH reactivity, if compared to adequate control tranfers. In this model the target animal for T cell reactivity (the AB recipient) remains untouched from immunosuppressive regimen.", "contents": "Inhibition of T cell activity in vivo: a test model for quantitative evaluation. A test model is presented which, in comparison with the conventional models of skin transplantation or graft-versus-host (GvH) reaction in mice, permits a more sensitive quantitative evaluation of T cell inhibition in vivo. Prospective donors (type AA) are immunized with prospective recipient material (type AB); the resulting T cell reaction of A versus B is inhibited by consecutive treatment. Extent of inhibition can be evaluated after transfer of the pretreated AA material onto AB recipients by calculation of remaining GvH reactivity, if compared to adequate control tranfers. In this model the target animal for T cell reactivity (the AB recipient) remains untouched from immunosuppressive regimen."}
{"id": "PMID:11100", "title": "Antibody response to phosphorylcholine in vitro. II. Analysis of T-dependent and T-independent responses.", "content": "Spleen cells from BALB/c mice primed with keyhole limpet hemocyanin (KLH), were stimulated with heat-killed vaccine of rough Pneumococcus pneumoniae R36A (Pn) and/or phosphorylcholine (PC)-coupled KLH to induce an anti-PC response in vitro. The response to PC-KLH was found to be T-dependent while it is T-independent to Pn. The antibodies induced with either antigen had similar avidity and expressed the TEPC 15 idiotype exclusively; thus T cell involvement in the response to PC-KLH failed to alter these parameters of the anti-PC response. At the precursor cell level, Pn induced small clones with an average size of 10 plaque-forming cells (PFC), whereas PC-KLH gave rise to larger clones of 40-50 PFC. This difference in the proliferative potential of PC precursor B cells hinted at the possibility that Pn and PC-KLH were stimulating different precursors. This was corroborated by the observation that a) when Pn and PC-KLH were added to the same cultures a synergistic effect was seen, i.e. the number of plaques was greater than the sum of the responses induced by each antigen, and b) in microcultures, under conditions limiting B cells only, Pn plus PC-KLH induced a higher fraction of responding wells than either antigen on its own. We postulate that Pn and PC-KLH stimulate subpopulations of PC precursor cells which are T-independent and T-dependent, respectively.", "contents": "Antibody response to phosphorylcholine in vitro. II. Analysis of T-dependent and T-independent responses. Spleen cells from BALB/c mice primed with keyhole limpet hemocyanin (KLH), were stimulated with heat-killed vaccine of rough Pneumococcus pneumoniae R36A (Pn) and/or phosphorylcholine (PC)-coupled KLH to induce an anti-PC response in vitro. The response to PC-KLH was found to be T-dependent while it is T-independent to Pn. The antibodies induced with either antigen had similar avidity and expressed the TEPC 15 idiotype exclusively; thus T cell involvement in the response to PC-KLH failed to alter these parameters of the anti-PC response. At the precursor cell level, Pn induced small clones with an average size of 10 plaque-forming cells (PFC), whereas PC-KLH gave rise to larger clones of 40-50 PFC. This difference in the proliferative potential of PC precursor B cells hinted at the possibility that Pn and PC-KLH were stimulating different precursors. This was corroborated by the observation that a) when Pn and PC-KLH were added to the same cultures a synergistic effect was seen, i.e. the number of plaques was greater than the sum of the responses induced by each antigen, and b) in microcultures, under conditions limiting B cells only, Pn plus PC-KLH induced a higher fraction of responding wells than either antigen on its own. We postulate that Pn and PC-KLH stimulate subpopulations of PC precursor cells which are T-independent and T-dependent, respectively."}
{"id": "PMID:11101", "title": "Mechanisms by which hapten conjugates of pneumococcal polysaccharide interfere with the challenge of anti-hapten memory cells.", "content": "Incubation of trinitrophenylated hemocyanin (TNP-KLH)-primed spleen cells with microgram amounts of 2,4-dinitrophenyl (DNP) or 2,4,6-trinitrophenyl (TNP) conjugates of pneumococcal polysaccharide type 3 (SIII) for as little as 5 min at 4 degrees C results in a specific \"block\" of the 19 S and 7 S adoptive memory response to TNP-KLH. This hapten-SIII-induced block of anti-hapten memory B cell responsiveness seems to be an example of specific receptor blockade. The block is specific and can be prevented by simultaneous incubation of the primed cells with hapten-protein conjugates which presumably compete with the hapten-polysaccharide for attachment to the B cell surface via anti-hapten Ig receptors. Removal via capping of these Ig receptors by exposure of TNP-KLH-primed memory cells to rabbit anti-mouse Fab serum for 45 min at 37 degrees C renders these cells refractory to the blocking effect of hapten-SIII. Once the hapten-SIII has attached to the memory cells, these blocked cells can be \"rescued\" (i.e. returned to a state of responsiveness) by incubating these cells with either mouse anti-SIII at 37 degrees C or rabbit anti-DNP serum at 4 degrees C. Since a papain digest of the IgG fraction of rabbit anti-DNP did not rescue the cells while the intact IgG did, a capping off of the TNP-SIII was proposed as the mechanims for this return to responsiveness of the hitherto blocked cells. A rescue was not seen by treatment of recipient mice with such B cell mitogens as dextran sulfate, endotoxin or purified protein derivative of tuberculin.", "contents": "Mechanisms by which hapten conjugates of pneumococcal polysaccharide interfere with the challenge of anti-hapten memory cells. Incubation of trinitrophenylated hemocyanin (TNP-KLH)-primed spleen cells with microgram amounts of 2,4-dinitrophenyl (DNP) or 2,4,6-trinitrophenyl (TNP) conjugates of pneumococcal polysaccharide type 3 (SIII) for as little as 5 min at 4 degrees C results in a specific \"block\" of the 19 S and 7 S adoptive memory response to TNP-KLH. This hapten-SIII-induced block of anti-hapten memory B cell responsiveness seems to be an example of specific receptor blockade. The block is specific and can be prevented by simultaneous incubation of the primed cells with hapten-protein conjugates which presumably compete with the hapten-polysaccharide for attachment to the B cell surface via anti-hapten Ig receptors. Removal via capping of these Ig receptors by exposure of TNP-KLH-primed memory cells to rabbit anti-mouse Fab serum for 45 min at 37 degrees C renders these cells refractory to the blocking effect of hapten-SIII. Once the hapten-SIII has attached to the memory cells, these blocked cells can be \"rescued\" (i.e. returned to a state of responsiveness) by incubating these cells with either mouse anti-SIII at 37 degrees C or rabbit anti-DNP serum at 4 degrees C. Since a papain digest of the IgG fraction of rabbit anti-DNP did not rescue the cells while the intact IgG did, a capping off of the TNP-SIII was proposed as the mechanims for this return to responsiveness of the hitherto blocked cells. A rescue was not seen by treatment of recipient mice with such B cell mitogens as dextran sulfate, endotoxin or purified protein derivative of tuberculin."}
{"id": "PMID:11102", "title": "Suprression of local graft-versus-host reactions by mouse fetal and newborn spleen cells.", "content": "Fetal splenic but not thymic lymphocytes significantly reduce the ability of parenteral adult spleen cells to elicit local graft-versus-host reactions in F1 recipients. This suppressive activity wanes early after birth. There is no requirement for histo compatibility between reacting and suppressor cells.", "contents": "Suprression of local graft-versus-host reactions by mouse fetal and newborn spleen cells. Fetal splenic but not thymic lymphocytes significantly reduce the ability of parenteral adult spleen cells to elicit local graft-versus-host reactions in F1 recipients. This suppressive activity wanes early after birth. There is no requirement for histo compatibility between reacting and suppressor cells."}
{"id": "PMID:11103", "title": "In vitro studies on smooth muscle of the human renal pelvis.", "content": "Isolated segments of human renal pelvis were studied by an isometric technique. Increases in tension following the addition of adrenaline, noradrenaline and phenylephrine were shown to be mediated via alpha-adrenoceptors. Similar responses to acetylcholine were demonstrated to be due to muscarinic receptor stimulation. Specimens responded to transmural electrical stimulation only when the pulse width was greater than 4 msec, and such responses were unaffected by pretreatment with tetrodotoxin, phentolamine and atropine. These experiments suggest that there is no effective innervation of the receptor sites identified, and hence that renal pelvis motility in vivo is not amenable to regulation by the autonomic nervous system.", "contents": "In vitro studies on smooth muscle of the human renal pelvis. Isolated segments of human renal pelvis were studied by an isometric technique. Increases in tension following the addition of adrenaline, noradrenaline and phenylephrine were shown to be mediated via alpha-adrenoceptors. Similar responses to acetylcholine were demonstrated to be due to muscarinic receptor stimulation. Specimens responded to transmural electrical stimulation only when the pulse width was greater than 4 msec, and such responses were unaffected by pretreatment with tetrodotoxin, phentolamine and atropine. These experiments suggest that there is no effective innervation of the receptor sites identified, and hence that renal pelvis motility in vivo is not amenable to regulation by the autonomic nervous system."}
{"id": "PMID:11104", "title": "Differential response control by isopropamide: a peripherally induced discriminative cue.", "content": "The peripherally acting anticholinergic drug isopropamide (0.02 mg/kg s.c.) is shown to produce a discriminative stimulus complex in rats. In rats trained to discriminate isopropamide from saline, dexetimide and methylscopolamine were generalized with isopropamide treatment. The results indicate that drug discrimination learning does not necessarily require a central drug action.", "contents": "Differential response control by isopropamide: a peripherally induced discriminative cue. The peripherally acting anticholinergic drug isopropamide (0.02 mg/kg s.c.) is shown to produce a discriminative stimulus complex in rats. In rats trained to discriminate isopropamide from saline, dexetimide and methylscopolamine were generalized with isopropamide treatment. The results indicate that drug discrimination learning does not necessarily require a central drug action."}
{"id": "PMID:11105", "title": "Antiarrhythmic action of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), compared with that of propranolol.", "content": "The antiarrhythmic activity of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), was compared with that of propranolol. KF-577 antagonized ouabain-induced arrhythmias in normal and bilaterally vagotomized guinea pigs; its antagonistic activity was equal to that of propranolol. Reserpinization greatly reduced ouabain intoxication and neither of the two beta-blockers produced further reduction. Aconitine-induced arrhythmias in rats were not antagonized by the two agents. In intact guinea pigs, the reduction of ouabain intoxication by both beta-blockers could not exceed that produced by simulataneous infusion of KCl, and vice versa. In isolated guinea pig atria, propranolol was about 10 times more effective than KF-577 in reducing the ouabain intoxication. The antiaarhythmic activity of KF-577 paralleled its beta-blocking activity in the isolated preparations but not in the intact animals.", "contents": "Antiarrhythmic action of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), compared with that of propranolol. The antiarrhythmic activity of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), was compared with that of propranolol. KF-577 antagonized ouabain-induced arrhythmias in normal and bilaterally vagotomized guinea pigs; its antagonistic activity was equal to that of propranolol. Reserpinization greatly reduced ouabain intoxication and neither of the two beta-blockers produced further reduction. Aconitine-induced arrhythmias in rats were not antagonized by the two agents. In intact guinea pigs, the reduction of ouabain intoxication by both beta-blockers could not exceed that produced by simulataneous infusion of KCl, and vice versa. In isolated guinea pig atria, propranolol was about 10 times more effective than KF-577 in reducing the ouabain intoxication. The antiaarhythmic activity of KF-577 paralleled its beta-blocking activity in the isolated preparations but not in the intact animals."}
{"id": "PMID:11106", "title": "Effects of drugs on the formation of homovanillic acid in the rat retina.", "content": "Homovanillic acid (HVA) levels were measured in the eye and the corpus striatum of rats under normal conditions and after different drug treatments. Neuroleptic agents such as clozapine, cis-flupenthixol and haloperidol induced comparable increases in HVA levels, whereas the non-neuroleptic trans-isomer of flupenthixol was inactive in both structures. Apomorphine decreased HVA levels in the retina and the corpus striatum, while amphetamine induced a decreased HVA formation in the retina and did not change levels of HVA in the corpus striatum. Probenecid caused a similar percentage rise of HVA in both structures. Morphine and oxotremorine induced a rise in HVA levels in the corpus striatum but not in retinal samples.", "contents": "Effects of drugs on the formation of homovanillic acid in the rat retina. Homovanillic acid (HVA) levels were measured in the eye and the corpus striatum of rats under normal conditions and after different drug treatments. Neuroleptic agents such as clozapine, cis-flupenthixol and haloperidol induced comparable increases in HVA levels, whereas the non-neuroleptic trans-isomer of flupenthixol was inactive in both structures. Apomorphine decreased HVA levels in the retina and the corpus striatum, while amphetamine induced a decreased HVA formation in the retina and did not change levels of HVA in the corpus striatum. Probenecid caused a similar percentage rise of HVA in both structures. Morphine and oxotremorine induced a rise in HVA levels in the corpus striatum but not in retinal samples."}
{"id": "PMID:11107", "title": "Relationship between the prevention of rat gastric erosions and the inhibition of acid secretion by prostaglandins.", "content": "The formation of gastric mucosal erosions induced by indomethacin in the rat was inhibited in a time- and dose-dependent manner by antisecretory prostaglandins, the methyl analogues of PGE2 being 400 times as active as the parent prostaglandin. PGA2, a methyl analogue of PGF2alpha and the H2-receptor antagonist metiamide, also inhibited erosion formation. There was a variable relationship between the doses required to inhibit erosions and to inhibit gastric acid secretion. In the anaesthetised rat, the low incidence of erosions with indomethacin was markedly increased by concurrent gastric perfusion with acid saline and taurocholate. This mucosal damage was inhibited by the methyl analogues of PGE2, suggesting protective actions on the mucosa other than inhibition of acid secretion.", "contents": "Relationship between the prevention of rat gastric erosions and the inhibition of acid secretion by prostaglandins. The formation of gastric mucosal erosions induced by indomethacin in the rat was inhibited in a time- and dose-dependent manner by antisecretory prostaglandins, the methyl analogues of PGE2 being 400 times as active as the parent prostaglandin. PGA2, a methyl analogue of PGF2alpha and the H2-receptor antagonist metiamide, also inhibited erosion formation. There was a variable relationship between the doses required to inhibit erosions and to inhibit gastric acid secretion. In the anaesthetised rat, the low incidence of erosions with indomethacin was markedly increased by concurrent gastric perfusion with acid saline and taurocholate. This mucosal damage was inhibited by the methyl analogues of PGE2, suggesting protective actions on the mucosa other than inhibition of acid secretion."}
{"id": "PMID:11108", "title": "Centrally induced reduction in sympathetic tone-a postsynaptic alpha-adrenoceptor-stimulating action of imidazolines.", "content": "Naphazoline or oxymetazoline (both 30 mug/kg) were injected into the cisterna magna of anaesthetized cats and reduced blood pressure, heart rate and the electrical discharge rate of small fibre bundles of the preganglionic sympathetic splanchnic nerve. Cats were depleted of endogenous noradrenaline by pretreatment with reserpine (5 mg/kg, 18 h) and alpha-methyl-p-tyrosine (twice 300 mg/kg, 18 and 2 h). In these animals, intracisternal injection of 30 mug/kg oxymetazoline exerted a decrease of sympathetic discharges similar to that described for non-pretreated animals. In noradrenaline-depleted cats intracisternal injection of 1 mug/kg clonidine also decreased the sympathetic discharges. It is concluded that these imidazolines exert their sympathoinhibitory and cardiovascular effects by stimulation of postsynaptic alpha-adrenoceptors in the CNS.", "contents": "Centrally induced reduction in sympathetic tone-a postsynaptic alpha-adrenoceptor-stimulating action of imidazolines. Naphazoline or oxymetazoline (both 30 mug/kg) were injected into the cisterna magna of anaesthetized cats and reduced blood pressure, heart rate and the electrical discharge rate of small fibre bundles of the preganglionic sympathetic splanchnic nerve. Cats were depleted of endogenous noradrenaline by pretreatment with reserpine (5 mg/kg, 18 h) and alpha-methyl-p-tyrosine (twice 300 mg/kg, 18 and 2 h). In these animals, intracisternal injection of 30 mug/kg oxymetazoline exerted a decrease of sympathetic discharges similar to that described for non-pretreated animals. In noradrenaline-depleted cats intracisternal injection of 1 mug/kg clonidine also decreased the sympathetic discharges. It is concluded that these imidazolines exert their sympathoinhibitory and cardiovascular effects by stimulation of postsynaptic alpha-adrenoceptors in the CNS."}
{"id": "PMID:11109", "title": "Contribution of granulocytopenia to endotoxin sensitivity of mice irradiated or undergoing graft-versus-host reaction.", "content": "Animals compromised by irradiation or graft-versus-host reaction (GVHR) are highly sensitive to endotoxin (ET). In order to determine the causes of the increased sensitivity of compromised mice, we studied alterations of hepatic (central) and bloodborne (peripheral) ET clearance processes. We observed that increased sensitivity to ET, as determined by mortality, occurred shortly after irradiation and correlated with granulocytopenia nd thrombocytopenia rather than with impairment of liver function. The involvement of granulocytes in ET clearance was indicated by injection of 51Cr-ET suspended in whole blood. By comparison with clearance of ET injected with saline or plasma, greater amounts of 51Cr-ET were sequestered in peripheral organs than in the liver. Similar results were obtained when Cr-ET in whole blood was perfused through a rat liver. ET clearance was enhanced 50% over that seen in M-199, plasma, or platelet-rich plasma. It was also found that intestinal ET contributes to mortality of granulocytopenic-thrombocytopenic mice. This was supported by the observation that bacteriologically decontaminated, irradiated animals were eight times more resistant to challenge with ET than were conventional animals. Thus, an important aspect of increased sensitivity to ET, in comprised mice, is defective peripheral clearance.", "contents": "Contribution of granulocytopenia to endotoxin sensitivity of mice irradiated or undergoing graft-versus-host reaction. Animals compromised by irradiation or graft-versus-host reaction (GVHR) are highly sensitive to endotoxin (ET). In order to determine the causes of the increased sensitivity of compromised mice, we studied alterations of hepatic (central) and bloodborne (peripheral) ET clearance processes. We observed that increased sensitivity to ET, as determined by mortality, occurred shortly after irradiation and correlated with granulocytopenia nd thrombocytopenia rather than with impairment of liver function. The involvement of granulocytes in ET clearance was indicated by injection of 51Cr-ET suspended in whole blood. By comparison with clearance of ET injected with saline or plasma, greater amounts of 51Cr-ET were sequestered in peripheral organs than in the liver. Similar results were obtained when Cr-ET in whole blood was perfused through a rat liver. ET clearance was enhanced 50% over that seen in M-199, plasma, or platelet-rich plasma. It was also found that intestinal ET contributes to mortality of granulocytopenic-thrombocytopenic mice. This was supported by the observation that bacteriologically decontaminated, irradiated animals were eight times more resistant to challenge with ET than were conventional animals. Thus, an important aspect of increased sensitivity to ET, in comprised mice, is defective peripheral clearance."}
{"id": "PMID:11110", "title": "Mitigation of Graft-versus-host disease in mice with xenogeneic antithymocyte serum and complement.", "content": "In vitro treatment of parental C57BL/6 lymphohematopoietic cell grafts with unabsorbed guinea pig anti-mouse thymocyte serum (ATS) and guinea pig complement (GPC), prior to inoculation into lethally irradiated B6D2F hybrid hosts, has proven to be of value in terms of mitigating graft-versus-host disease (GvHD). However, the beneficial effect of such a pregrafting procedure is limited to the prevention of acute GvHD. The late GvHD remains a continuing problem, and is probably due to the graft-versus-host activity (GvHA) of newly produced nontolerant lymphocytes from lymphoid precursors resistant to ATS. Possible ways to render these precursors sensitive to ATS and complement are discussed. The potential significance of thymic hormones and cyclic AMP in achieving this is emphasized.", "contents": "Mitigation of Graft-versus-host disease in mice with xenogeneic antithymocyte serum and complement. In vitro treatment of parental C57BL/6 lymphohematopoietic cell grafts with unabsorbed guinea pig anti-mouse thymocyte serum (ATS) and guinea pig complement (GPC), prior to inoculation into lethally irradiated B6D2F hybrid hosts, has proven to be of value in terms of mitigating graft-versus-host disease (GvHD). However, the beneficial effect of such a pregrafting procedure is limited to the prevention of acute GvHD. The late GvHD remains a continuing problem, and is probably due to the graft-versus-host activity (GvHA) of newly produced nontolerant lymphocytes from lymphoid precursors resistant to ATS. Possible ways to render these precursors sensitive to ATS and complement are discussed. The potential significance of thymic hormones and cyclic AMP in achieving this is emphasized."}
{"id": "PMID:11111", "title": "Acid mucopolysaccharides in fibroblast cultures. 1. Influence of cell density, pH-value and lactate concentration on the MPS distribution pattern.", "content": "From cells and culture media of embryonic rat fibroblasts (1st subculture) the acid mucopolysaccharides were isolated and fractionated. The per cent calculation of the 6 fractions was based on the content of glucuronic acid. The cultures were maintained as follows: 0.5 X 10(6) to 3 X 10(6) cells were examined in Demeter flasks at pH 7.4 or 6.6; lactate concentration was enhanced to 100 mg%. The amount of each fraction was correlated with the cell density (linear regression). The pH-value and lactate concentration in connection with cell density proved to be important factors in the modification of the MPS distribution pattern.", "contents": "Acid mucopolysaccharides in fibroblast cultures. 1. Influence of cell density, pH-value and lactate concentration on the MPS distribution pattern. From cells and culture media of embryonic rat fibroblasts (1st subculture) the acid mucopolysaccharides were isolated and fractionated. The per cent calculation of the 6 fractions was based on the content of glucuronic acid. The cultures were maintained as follows: 0.5 X 10(6) to 3 X 10(6) cells were examined in Demeter flasks at pH 7.4 or 6.6; lactate concentration was enhanced to 100 mg%. The amount of each fraction was correlated with the cell density (linear regression). The pH-value and lactate concentration in connection with cell density proved to be important factors in the modification of the MPS distribution pattern."}
{"id": "PMID:11112", "title": "Acid mucopolysaccharides in fibroblast cultures. 2. 35S-sulfate incorporation kinetics in dependence on pH-value and cell density.", "content": "Cultures of embryonic rat fibroblasts were incubated with 35S-sulfate at pH 6.6 and 7.4 (Eagle basal medium plus HEPES buffer) for 12 to 48 hours. The acid mucopolysaccharides were isolated and fractionated after the method of SVEJCAR and ROBERTSON. Sulfate incorporation was determined by liquid scintillation counting.", "contents": "Acid mucopolysaccharides in fibroblast cultures. 2. 35S-sulfate incorporation kinetics in dependence on pH-value and cell density. Cultures of embryonic rat fibroblasts were incubated with 35S-sulfate at pH 6.6 and 7.4 (Eagle basal medium plus HEPES buffer) for 12 to 48 hours. The acid mucopolysaccharides were isolated and fractionated after the method of SVEJCAR and ROBERTSON. Sulfate incorporation was determined by liquid scintillation counting."}
{"id": "PMID:11114", "title": "Allantoinase in the marine polychaete Eudistylia vancouveri.", "content": "Allantoinase, an enzyme in the purine-urea cycle, was found in Eudistylia vancouveri (Polychaeta). The enzyme had a pH optimum at 7.6. The Km was 0.012 M allantoin, and the Arrhenius energy of activation was 12.6 to 14.6 kcal/mol.", "contents": "Allantoinase in the marine polychaete Eudistylia vancouveri. Allantoinase, an enzyme in the purine-urea cycle, was found in Eudistylia vancouveri (Polychaeta). The enzyme had a pH optimum at 7.6. The Km was 0.012 M allantoin, and the Arrhenius energy of activation was 12.6 to 14.6 kcal/mol."}
{"id": "PMID:11116", "title": "Influence of the trypsin activity by the side chain of arginine homologues.", "content": "The N-alpha-tosyl-p-nitroanilides of homoarginine and of the two shorter arginine homologues were synthesized. These compounds behave as specific, chromogenic substrates for trypsin.", "contents": "Influence of the trypsin activity by the side chain of arginine homologues. The N-alpha-tosyl-p-nitroanilides of homoarginine and of the two shorter arginine homologues were synthesized. These compounds behave as specific, chromogenic substrates for trypsin."}
{"id": "PMID:11117", "title": "Beta-adrenergic receptors in rat myocardium: direct detection by a new fluorescent beta-blocker.", "content": "A new fluorescent beta-blocker, 9-amino-acridin propranolol (9-AAP), was administered i.v. to rats. Multiple fluorescent 9-AAP binding sites were observed on cardiac muscle cells in frozen sections. Intensity and density of cardiac 9-AAP fluorescence were markedly reduced following pretreatment with (+/-)- and (-)-propranolol but not with (+)-propranolol. Our findings suggest that 9-AAP may label beta-adrenergic receptor sites in rat myocardium.", "contents": "Beta-adrenergic receptors in rat myocardium: direct detection by a new fluorescent beta-blocker. A new fluorescent beta-blocker, 9-amino-acridin propranolol (9-AAP), was administered i.v. to rats. Multiple fluorescent 9-AAP binding sites were observed on cardiac muscle cells in frozen sections. Intensity and density of cardiac 9-AAP fluorescence were markedly reduced following pretreatment with (+/-)- and (-)-propranolol but not with (+)-propranolol. Our findings suggest that 9-AAP may label beta-adrenergic receptor sites in rat myocardium."}
{"id": "PMID:11118", "title": "Histamine-induced hypotension modified by H1 and H2 antagonists in the monkey (Macaca mulatta).", "content": "Blocking H2 receptors with burimamide in the dose used (20 mg/kg) approximately doubles the amount of histamine needed to produce the same effect as seen when H1 antagonists (chlorpheniramine or mepyramine) are used alone. The Kz ratios for chlorpheniramine-chlorpheniramine plus burimamide are 117-204 and for mepyramine-mepyramine phus burimamide are 200-478. H1 and H2 receptors, in the monkey, when stimulated, both cause cardiovascular responses in the same direction.", "contents": "Histamine-induced hypotension modified by H1 and H2 antagonists in the monkey (Macaca mulatta). Blocking H2 receptors with burimamide in the dose used (20 mg/kg) approximately doubles the amount of histamine needed to produce the same effect as seen when H1 antagonists (chlorpheniramine or mepyramine) are used alone. The Kz ratios for chlorpheniramine-chlorpheniramine plus burimamide are 117-204 and for mepyramine-mepyramine phus burimamide are 200-478. H1 and H2 receptors, in the monkey, when stimulated, both cause cardiovascular responses in the same direction."}
{"id": "PMID:11119", "title": "The oxygen-linked hydrogen ion binding (the Haldane coefficient) of bovine hemoglobin.", "content": "The Haldane coefficient (the amount of the oxygen-linked hydrogen ion binding of hemoglobin) was determined in bovine erythrolysate (Hb concentration equals 13.5 mM) by means of the differential titration method with varying PCO2 from 0 to 74 mm Hg and pH from 6.0 to 8.5 at 37 degrees C. The maximum value of the coefficient was found to be 0.49 mM per mM Hb at PCO2 equals 0 and pH 7.20. With increasing of PCO2, the coefficient became smaller in all ranges of pH studied. The coefficient under the conditions of pH 7.20 and PCO2 equals 45 mm Hg that are normally prevailing in the interior of bovine erythrocytes was 0.31.", "contents": "The oxygen-linked hydrogen ion binding (the Haldane coefficient) of bovine hemoglobin. The Haldane coefficient (the amount of the oxygen-linked hydrogen ion binding of hemoglobin) was determined in bovine erythrolysate (Hb concentration equals 13.5 mM) by means of the differential titration method with varying PCO2 from 0 to 74 mm Hg and pH from 6.0 to 8.5 at 37 degrees C. The maximum value of the coefficient was found to be 0.49 mM per mM Hb at PCO2 equals 0 and pH 7.20. With increasing of PCO2, the coefficient became smaller in all ranges of pH studied. The coefficient under the conditions of pH 7.20 and PCO2 equals 45 mm Hg that are normally prevailing in the interior of bovine erythrocytes was 0.31."}
{"id": "PMID:11120", "title": "Activation of sustained sympathetic vasodilatation in dog by spinal cord stimulation.", "content": "Electrical stimulation in lateral sites of the upper cervical spinal cord evoked vasodilatation after adrenergic blockade. Sympathetic fibres mediating sustained vasodilatation were shown to be separate from adrenergic sympathetic fibres since the adrenergic vasoconstrictor response in the paw evoked by vasomotor stimulation in the medulla was not reversed to vasodilatation after bretylium.", "contents": "Activation of sustained sympathetic vasodilatation in dog by spinal cord stimulation. Electrical stimulation in lateral sites of the upper cervical spinal cord evoked vasodilatation after adrenergic blockade. Sympathetic fibres mediating sustained vasodilatation were shown to be separate from adrenergic sympathetic fibres since the adrenergic vasoconstrictor response in the paw evoked by vasomotor stimulation in the medulla was not reversed to vasodilatation after bretylium."}
{"id": "PMID:11121", "title": "Effects of morphine administration on cerebellar guanosine 3',5'-monophosphate.", "content": "An increase in mouse cerebellar C-GMP levels during acute morphine treatment was observed, which was possibly related to the decrease in C-GMP phosphodiesterase levels also observed in acute treatment. Chronic treatment lowered C-GMP levels as did abrupt withdrawal without naloxone.", "contents": "Effects of morphine administration on cerebellar guanosine 3',5'-monophosphate. An increase in mouse cerebellar C-GMP levels during acute morphine treatment was observed, which was possibly related to the decrease in C-GMP phosphodiesterase levels also observed in acute treatment. Chronic treatment lowered C-GMP levels as did abrupt withdrawal without naloxone."}
{"id": "PMID:11122", "title": "[Effect of liver damage by thioacetamide on microsomal aromatization of testosterone in rats (author's transl)].", "content": "Rat liver microsomes, NADPH-regenerating system, and 1beta, 2beta-3H-testosterone have been incubated in vitro. The loss of tritium from the steroid, associated with aromatization of testosterone, was linear with time for 20 min and required NADPH. Pre-treatment of the rats with thioacetamide raised the liberation of tritium from 1beta, 2beta-3H-testosterone. The results suggest that liver damage by thioacetamide in rats may give rise to increased aromatization of testosterone.", "contents": "[Effect of liver damage by thioacetamide on microsomal aromatization of testosterone in rats (author's transl)]. Rat liver microsomes, NADPH-regenerating system, and 1beta, 2beta-3H-testosterone have been incubated in vitro. The loss of tritium from the steroid, associated with aromatization of testosterone, was linear with time for 20 min and required NADPH. Pre-treatment of the rats with thioacetamide raised the liberation of tritium from 1beta, 2beta-3H-testosterone. The results suggest that liver damage by thioacetamide in rats may give rise to increased aromatization of testosterone."}
{"id": "PMID:11136", "title": "Reduction of the graft-versus-host reactivity of mouse and rat spleen cells by 5alpha-androstane-3,17-dione.", "content": "The local graft-versus-host reaction as evaluated by the popliteal lymph node enlargement was used for studying the immunosuppressive potency of placental steroid 5alpha-androstane-3,17-dione. Spleen cells from virgin female mice and rats injected subcutaneously with this steroid compound produced in appropriate F1 recipients a significantly weaker reaction (P less than 0.001) than spleen cells from untreated or medium-treated control animals. On the other hand, the pretreatment of cell donors either with 5beta-androstane-3,17-dione or testosterone, the compounds which are not present in the mouse and rat placenta, did not influence the normal graft-versus-host reactivity.", "contents": "Reduction of the graft-versus-host reactivity of mouse and rat spleen cells by 5alpha-androstane-3,17-dione. The local graft-versus-host reaction as evaluated by the popliteal lymph node enlargement was used for studying the immunosuppressive potency of placental steroid 5alpha-androstane-3,17-dione. Spleen cells from virgin female mice and rats injected subcutaneously with this steroid compound produced in appropriate F1 recipients a significantly weaker reaction (P less than 0.001) than spleen cells from untreated or medium-treated control animals. On the other hand, the pretreatment of cell donors either with 5beta-androstane-3,17-dione or testosterone, the compounds which are not present in the mouse and rat placenta, did not influence the normal graft-versus-host reactivity."}
{"id": "PMID:11137", "title": "The sensitivity of chromatin from thymuses and spleens of irradiated mice to alkaline solutions.", "content": "Increasing amounts of DNA and proteins are released from the suspensions of chromatin from thymuses and spleens of irradiated mice (6 hours after 600R whole-body) by the action of alkaline solutions (pH 8-10) at physiological ionic strengths. The suspension of chromatin from normal tissues releases in this pH range only a small amount of proteins and negligible amount of DNA. The behaviour of liver and kidney chromatin to alkaline solutions shows no difference between normal and irradiated tissues. The time of onset and dose relation of the increased sensitivity of thymus and spleen chromatin from irradiated mice to alkaline solutions show a similar course as earlier described signs of postirradiation damage to chromatin of these tissues.", "contents": "The sensitivity of chromatin from thymuses and spleens of irradiated mice to alkaline solutions. Increasing amounts of DNA and proteins are released from the suspensions of chromatin from thymuses and spleens of irradiated mice (6 hours after 600R whole-body) by the action of alkaline solutions (pH 8-10) at physiological ionic strengths. The suspension of chromatin from normal tissues releases in this pH range only a small amount of proteins and negligible amount of DNA. The behaviour of liver and kidney chromatin to alkaline solutions shows no difference between normal and irradiated tissues. The time of onset and dose relation of the increased sensitivity of thymus and spleen chromatin from irradiated mice to alkaline solutions show a similar course as earlier described signs of postirradiation damage to chromatin of these tissues."}
{"id": "PMID:11138", "title": "Some biological properties of mouse spleen cells fractionated by the adherence of Sephadex G 25 and glass bead columns.", "content": "The possibilities of separation of haemopoietic cells from lymphocytes capable of eliciting the graft-versus-host reaction through column chromatography were investigated. Strain-A mouse spleen cells were fractionated into the adherent and non-adherent fraction on Sephadex G-25, glass bead columns and glass beads coated with antibody against mouse globulin. Increased numbers of cells forming haemopoietic colonies were found in the cell fraction which did not adhere to the antibody-coated glass beads and in cells reversibly adhering to glass beads. No significant decrease in local graft-versus-host reaction was found in any fraction obtained, and the prolonged survival of irradiated semiallogeneic recipients was observed in both fractions obtained on Sephadex G-25 columns.", "contents": "Some biological properties of mouse spleen cells fractionated by the adherence of Sephadex G 25 and glass bead columns. The possibilities of separation of haemopoietic cells from lymphocytes capable of eliciting the graft-versus-host reaction through column chromatography were investigated. Strain-A mouse spleen cells were fractionated into the adherent and non-adherent fraction on Sephadex G-25, glass bead columns and glass beads coated with antibody against mouse globulin. Increased numbers of cells forming haemopoietic colonies were found in the cell fraction which did not adhere to the antibody-coated glass beads and in cells reversibly adhering to glass beads. No significant decrease in local graft-versus-host reaction was found in any fraction obtained, and the prolonged survival of irradiated semiallogeneic recipients was observed in both fractions obtained on Sephadex G-25 columns."}
{"id": "PMID:11140", "title": "Dopamine as a possible neurotransmitter in gastric relaxation.", "content": "In dogs with gastric fistulas, intragastric pressure was measured with a flaccid ballon containing 500 ml of water. Graded doses of dopamine caused graded decreases in intragastric pressure. The effect was blocked by pimozide or by metoclopramide but was not significantly affected by phenoxybenzamine, propranolol, guanethidine, or FLA-63 (a beta-hydroxylase inhibitor). Pretreatment with metoclopramide or with pimozide shifted the volume-pressure diagram of the stomach to the left; that is, at any given volume the pressure was greater after than before these drugs. In dogs with vagally innervated gastric pouches and gastric fistulas, feeding for 1 min (while allowing the food to leave the stomach through the gastric fistula) caused a prompt decrease in pressure in the pouch that lasted for about 5 min. Pretreatment with metoclopramide decreased the magnitude and duration of this receptive relaxation. It is concluded that these findings are consistent with (but do not establish) the hypothesis that dopamine is the neurotransmitter for receptive relaxation of the stomach, because dopamine mimics receptive relaxation, and dopamine antagonists partially block reflexly induced receptive relaxation.", "contents": "Dopamine as a possible neurotransmitter in gastric relaxation. In dogs with gastric fistulas, intragastric pressure was measured with a flaccid ballon containing 500 ml of water. Graded doses of dopamine caused graded decreases in intragastric pressure. The effect was blocked by pimozide or by metoclopramide but was not significantly affected by phenoxybenzamine, propranolol, guanethidine, or FLA-63 (a beta-hydroxylase inhibitor). Pretreatment with metoclopramide or with pimozide shifted the volume-pressure diagram of the stomach to the left; that is, at any given volume the pressure was greater after than before these drugs. In dogs with vagally innervated gastric pouches and gastric fistulas, feeding for 1 min (while allowing the food to leave the stomach through the gastric fistula) caused a prompt decrease in pressure in the pouch that lasted for about 5 min. Pretreatment with metoclopramide decreased the magnitude and duration of this receptive relaxation. It is concluded that these findings are consistent with (but do not establish) the hypothesis that dopamine is the neurotransmitter for receptive relaxation of the stomach, because dopamine mimics receptive relaxation, and dopamine antagonists partially block reflexly induced receptive relaxation."}
{"id": "PMID:11141", "title": "Inhibition of intestinal iron absorption by laundry starch.", "content": "The pathogenesis of iron deficiency anemia associated with amylophagia is usually attributed to dietary iron lack. However, large quantities of starch may inhibit intestinal iron absorption. Accordingly, studies were carried out to determine the effect of laundry starch on the intestinal absorption of inorganic and hemoglobin iron. In vitro, laundry starch bound 19 to 80% of the available 59FeSO4 and 34 to 68% of the available 59Fe-hemoglobin. Binding of both forms of iron was pH-dependent, with maximal binding at pH 7.0. In vivo, laundry starch significantly inhibited mucosal uptake of 59FeSO4 from isolated duodenal loops. In nonanemic rats, administration of laundry starch (100 mg) 1 hr before a 100-mug dose of 59FeSO4 significantly decreased the absorption of 59FeSO4, as compared to saline or low iron chow controls (6.2 +/- 2.0 versus 14.9 +/- 2.1 and -1.8 +/- 1.7, respectively, P less than 0.001). In anemic rats the absorption of either a 100-mug dose of 59FeSO4 or a 500-mug dose of 59Fe-hemoglobin was also significantly decreased by prior administration of laundry starch. The data obtained indicated that laundry starch (1) binds appreciable quantities of inorganic and hemoglobin iron in vitro; (2) inhibits the mucosal uptake or inorganic iron by isolated intestinal loops; (3) inhibits the intestinal absorption of inorganic iron in normal nonanemic rats, and (4) blunts the compensatory increase in inorganic and organic iron absorption in anemic rats.", "contents": "Inhibition of intestinal iron absorption by laundry starch. The pathogenesis of iron deficiency anemia associated with amylophagia is usually attributed to dietary iron lack. However, large quantities of starch may inhibit intestinal iron absorption. Accordingly, studies were carried out to determine the effect of laundry starch on the intestinal absorption of inorganic and hemoglobin iron. In vitro, laundry starch bound 19 to 80% of the available 59FeSO4 and 34 to 68% of the available 59Fe-hemoglobin. Binding of both forms of iron was pH-dependent, with maximal binding at pH 7.0. In vivo, laundry starch significantly inhibited mucosal uptake of 59FeSO4 from isolated duodenal loops. In nonanemic rats, administration of laundry starch (100 mg) 1 hr before a 100-mug dose of 59FeSO4 significantly decreased the absorption of 59FeSO4, as compared to saline or low iron chow controls (6.2 +/- 2.0 versus 14.9 +/- 2.1 and -1.8 +/- 1.7, respectively, P less than 0.001). In anemic rats the absorption of either a 100-mug dose of 59FeSO4 or a 500-mug dose of 59Fe-hemoglobin was also significantly decreased by prior administration of laundry starch. The data obtained indicated that laundry starch (1) binds appreciable quantities of inorganic and hemoglobin iron in vitro; (2) inhibits the mucosal uptake or inorganic iron by isolated intestinal loops; (3) inhibits the intestinal absorption of inorganic iron in normal nonanemic rats, and (4) blunts the compensatory increase in inorganic and organic iron absorption in anemic rats."}
{"id": "PMID:11142", "title": "Effect of serotonin on water and electrolyte transport in the in vivo rabbit small intestine.", "content": "The influence of intravenously administered serotonin on water and electrolyte fluxes in the in vivo rabbit jejunum and ileum was examined. Animals were divided into four groups: (1) those receiving saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) serotonin given intravenously while glucose-free intestinal perfusate was used as in group 1; (3) intravenous saline given while a 10 mM glucose-isotonic saline solution perfused the jejunum and ileum; and (4) intravenous serotonin given while the intestinal perfusate was as in group 3. Serotonin administration resulted in highly significant net secretion of H2O and sodium in both jejunum and ileum in the groups with a glucose-free perfusate. In jejunum, serotonin evoked net water and sodium secretion, whereas controls absorbed water and sodium. In ileum, serotonin significantly enhanced secretion. The addition of glucose to the perfusate completely abolished the serotonin effect. Unidirectional 22Na flux analysis revealed a marked diminution in both mucosal to serosal and serosal to mucosal fluxes in serotonin-treated animals. The decrease in mucosal to serosal flux was greater than the decrease in serosal to mucosal flux, thus explaining the enhanced net secretion observed with serotonin in the groups receiving glucose-free perfusate. In spite of its pronounced effect on water and electrolyte transport, serotonin failed to produce any detectable histological alterations in small bowel mucosa, either by light or electron microscopy. We postulate that serotonin may be an important mediator of the diarrhea so frequently noted in the carcinoid syndrome by virtue of its effects on small intestinal H2O and electrolyte transport.", "contents": "Effect of serotonin on water and electrolyte transport in the in vivo rabbit small intestine. The influence of intravenously administered serotonin on water and electrolyte fluxes in the in vivo rabbit jejunum and ileum was examined. Animals were divided into four groups: (1) those receiving saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) serotonin given intravenously while glucose-free intestinal perfusate was used as in group 1; (3) intravenous saline given while a 10 mM glucose-isotonic saline solution perfused the jejunum and ileum; and (4) intravenous serotonin given while the intestinal perfusate was as in group 3. Serotonin administration resulted in highly significant net secretion of H2O and sodium in both jejunum and ileum in the groups with a glucose-free perfusate. In jejunum, serotonin evoked net water and sodium secretion, whereas controls absorbed water and sodium. In ileum, serotonin significantly enhanced secretion. The addition of glucose to the perfusate completely abolished the serotonin effect. Unidirectional 22Na flux analysis revealed a marked diminution in both mucosal to serosal and serosal to mucosal fluxes in serotonin-treated animals. The decrease in mucosal to serosal flux was greater than the decrease in serosal to mucosal flux, thus explaining the enhanced net secretion observed with serotonin in the groups receiving glucose-free perfusate. In spite of its pronounced effect on water and electrolyte transport, serotonin failed to produce any detectable histological alterations in small bowel mucosa, either by light or electron microscopy. We postulate that serotonin may be an important mediator of the diarrhea so frequently noted in the carcinoid syndrome by virtue of its effects on small intestinal H2O and electrolyte transport."}
{"id": "PMID:11144", "title": "Lower esophageal sphincter response to oral administration of cimetidine in normal subjects.", "content": "Anithistamines that specifically block the gastric and secretory action of histamine have recently been developed. One of these H2-receptor blockers, metiamide, has been found to increase lower esophageal sphincter (LES) pressure in the opossum. Because of reported agranulocytosis with metiamide, another H2-receptor blocking agent, cimetidine, was developed. To determine its effect on LES pressure, 8 normal volunteers received placebo or oral doses of cimetidine (50, 100, 200, and 400 mg) in a random, blinded manner. Indicative of adequate absorption, significant serum levels were achieved with all doses of cimetidine (50 mg = 0.17 mug per ml; 100 mg = 0.33 mug per ml; 200 mg = 0.76 mug per ml; and 400 mg = 1.61 mug per ml). Although these serum levels have been found to produce marked inhibition of gastric acid secretion, no discernible effect was found on LES pressure when compared to placebo. Thus cimetidine does not increase LES pressure. It does not decrease sphincter pressure either and is therefore not contraindicated in patients with reflux esophagitis.", "contents": "Lower esophageal sphincter response to oral administration of cimetidine in normal subjects. Anithistamines that specifically block the gastric and secretory action of histamine have recently been developed. One of these H2-receptor blockers, metiamide, has been found to increase lower esophageal sphincter (LES) pressure in the opossum. Because of reported agranulocytosis with metiamide, another H2-receptor blocking agent, cimetidine, was developed. To determine its effect on LES pressure, 8 normal volunteers received placebo or oral doses of cimetidine (50, 100, 200, and 400 mg) in a random, blinded manner. Indicative of adequate absorption, significant serum levels were achieved with all doses of cimetidine (50 mg = 0.17 mug per ml; 100 mg = 0.33 mug per ml; 200 mg = 0.76 mug per ml; and 400 mg = 1.61 mug per ml). Although these serum levels have been found to produce marked inhibition of gastric acid secretion, no discernible effect was found on LES pressure when compared to placebo. Thus cimetidine does not increase LES pressure. It does not decrease sphincter pressure either and is therefore not contraindicated in patients with reflux esophagitis."}
{"id": "PMID:11145", "title": "The role of histamine receptors in the pathophysiology of gastric mucosal damage.", "content": "In four canine Heidenhain pouches the net fluxes of H+ and Na+ have been examined before, during, and after instillation of sodium taurocholate into the pouch. These experiments were conducted in animals given H1 (mepyramine maleate) and H2 (metiamide) histamine antagonists, alone and in combination. Control experiments without antagonists were also conducted. In control experiments, as well as in those using  the histamine antagonists separately, the usual sequence of events followed exposure to taurocholate-that is, a gain in the volume of the solution in the pouch and an increase in the fluxes of Na+ and H+ across the mucosa. In experiments in which H1 and H2 histamine antagonists were used in combination, taurocholate had very little effect on the ionic fluxes of H+ and Na+, suggesting that changes in the ionic permeability of the gastric mucosal barrier are mediated by histamine through both H1 and H2 receptor sites.", "contents": "The role of histamine receptors in the pathophysiology of gastric mucosal damage. In four canine Heidenhain pouches the net fluxes of H+ and Na+ have been examined before, during, and after instillation of sodium taurocholate into the pouch. These experiments were conducted in animals given H1 (mepyramine maleate) and H2 (metiamide) histamine antagonists, alone and in combination. Control experiments without antagonists were also conducted. In control experiments, as well as in those using  the histamine antagonists separately, the usual sequence of events followed exposure to taurocholate-that is, a gain in the volume of the solution in the pouch and an increase in the fluxes of Na+ and H+ across the mucosa. In experiments in which H1 and H2 histamine antagonists were used in combination, taurocholate had very little effect on the ionic fluxes of H+ and Na+, suggesting that changes in the ionic permeability of the gastric mucosal barrier are mediated by histamine through both H1 and H2 receptor sites."}
{"id": "PMID:11146", "title": "Properties of gastric antrum. III. Selectivity and modification of shunt conductance.", "content": "The permselectivity of the paracellular pathway of amphibian (Necturus and bullfrog) antrum was investigated with respect to intracationic selectivity and the K+ and Cl- permeability ratio as a function of mucosal pH. The intracationic selectivity sequence was Rb+ greater than K+ greater than Cs+ greater than Na+ greater than Li+. Both antra showed weak cationic selectivity at pH 7.4, and at pH 4.4 for bullfrog and pH 3.0 for Necturus, the ratio Pk+/P Cl- was unity. At lower mucosal pH the tissues were anion selective. Treatment of the tissue with a water-soluble carbodiimide enhanced anion selectivity at higher pH; carbenoxolone, a weak acid, resulted in maintained cation selectivity at lower pH. These data suggest that carboxyl groups play a role in determining shunt selectivity; the increase in anion selectivity below pH 2.0 suggests that phosphate or sulfate groups could also be involved.", "contents": "Properties of gastric antrum. III. Selectivity and modification of shunt conductance. The permselectivity of the paracellular pathway of amphibian (Necturus and bullfrog) antrum was investigated with respect to intracationic selectivity and the K+ and Cl- permeability ratio as a function of mucosal pH. The intracationic selectivity sequence was Rb+ greater than K+ greater than Cs+ greater than Na+ greater than Li+. Both antra showed weak cationic selectivity at pH 7.4, and at pH 4.4 for bullfrog and pH 3.0 for Necturus, the ratio Pk+/P Cl- was unity. At lower mucosal pH the tissues were anion selective. Treatment of the tissue with a water-soluble carbodiimide enhanced anion selectivity at higher pH; carbenoxolone, a weak acid, resulted in maintained cation selectivity at lower pH. These data suggest that carboxyl groups play a role in determining shunt selectivity; the increase in anion selectivity below pH 2.0 suggests that phosphate or sulfate groups could also be involved."}
{"id": "PMID:11147", "title": "Effect of fundusectomy on serum and antral gastrin levels in rats.", "content": "In adult male rats, fundusectomy decreased acid secretion but significantly increased total antral gastrin and both fasting and food-stimulated serum gastrin levels. The rise in fasting serum gastrin could be inhibited by antral acidification, suggesting that decreased acidity caused postfundusectomy hypergastrinemia. The mechanism for the increase in total gastrin in antral tissue is probably the same. These studies provide a useful experimental model for the increasing of antral gastrin and for the production of hypergastrinemia.", "contents": "Effect of fundusectomy on serum and antral gastrin levels in rats. In adult male rats, fundusectomy decreased acid secretion but significantly increased total antral gastrin and both fasting and food-stimulated serum gastrin levels. The rise in fasting serum gastrin could be inhibited by antral acidification, suggesting that decreased acidity caused postfundusectomy hypergastrinemia. The mechanism for the increase in total gastrin in antral tissue is probably the same. These studies provide a useful experimental model for the increasing of antral gastrin and for the production of hypergastrinemia."}
{"id": "PMID:11148", "title": "Postprandial gastric, pancreatic, and biliary response to histamine H2-receptor antagonists active duodenal ulcer.", "content": "Histamine H2-receptor antagonists are potentially useful agents in duodenal ulcer and knowledge of their effect on postprandial digestive events will contribute to their clinical application. We studied the effect of 200- and 300-mg doses of cimetidine, an H2-receptor antagonist, taken with an ordinary meal, on gastric, pancreatic, and biliary function. Both doses significantly reduced acid output and its delivery into the duodenum. Gastric secretory volume and pepsin output were less affected. Acid inhibition was related to blood drug levels and was less than that previously found at night in nocturnal fasting studies. As the stomach emptied the food, the gastric pH rose. The fractional gastric emptying rate, pancreatic enzyme, and bile acid outputs were unaltered. Cimetidine taken orally with meals at these doses is a potent gastric antisecretory agent without affecting other postprandial gastric, pancreatic, or biliary functions.", "contents": "Postprandial gastric, pancreatic, and biliary response to histamine H2-receptor antagonists active duodenal ulcer. Histamine H2-receptor antagonists are potentially useful agents in duodenal ulcer and knowledge of their effect on postprandial digestive events will contribute to their clinical application. We studied the effect of 200- and 300-mg doses of cimetidine, an H2-receptor antagonist, taken with an ordinary meal, on gastric, pancreatic, and biliary function. Both doses significantly reduced acid output and its delivery into the duodenum. Gastric secretory volume and pepsin output were less affected. Acid inhibition was related to blood drug levels and was less than that previously found at night in nocturnal fasting studies. As the stomach emptied the food, the gastric pH rose. The fractional gastric emptying rate, pancreatic enzyme, and bile acid outputs were unaltered. Cimetidine taken orally with meals at these doses is a potent gastric antisecretory agent without affecting other postprandial gastric, pancreatic, or biliary functions."}
{"id": "PMID:11149", "title": "Isolation and characterization of four peptide hydrolases from the cytosol of rat intestinal mucosa.", "content": "The high speed supernatant fluid prepared from rat intestinal mucosa was subjected to ion-exchange chromatography on diethlaminoethyl-cellulose eluted with a linear gradient of sodium chloride (0 to 0.27 M). Assay of eluted fractions for Phe-Gly hydrolase activity revealed four distinct peaks of enzyme activity. These cytosol enzymes have been designated I, II, III, and IV in order of their elution from the column. Examination of the substrate specificity of the four enzymes by use of 20 mM peptide concentrations indicated the most discriminating substrates for the four enzymes were Leu-Gly-Gly, His-Met, Ser-Phe, and leucine amide, respectively. The mean distribution of the recovered peptide hydrolase activities against these substrates among the four enzymes I, II, III, and IV was 96.1, 1.4, 1.7, and 0.8%, respectively, for Leu-Gly-Gly; 0.6, 96.4, 2.4, and 0.6% for His-Met; 0, 0, 95.8, and 4.2% for Ser-Phe; and 20.8, 19.8, 5.6, and 53.8% for leucine amide. Ion-exchange chromatography resulted in increases in specific activity of 19-, 19-, 46-, and 3.5-fold for enzymes I, II, III, and IV, respectively. The activity of all four enzymes, but especially III and IV, were stabilized by the presence of 150 muM dithioerythritol. Activity of each of the four enzymes was decreased 79 to 100% by 1mM ethylenediaminetetraacetate, HgCl2, 1, 10-phenanthroline, or 0.5 mM p-hydroxymercuribenzoate, except that the activity of enzyme I was decreased only 15% by ethylenediaminetetraacetate. No significant activation of the partially purified enzymes occurred in the presence of 500 muM Zn++, Co++, or Mg++. The four enzymes exhibited distinct pH profiles with optima at 7.5, 7.5, 8.5, and 8.0 for enzymes I, II, III, and IV, respectively. Molecular weights of the four enzymes determined by gel filtration on Sephadex G-200 were 58,500, 74,000, 97,500, and 113,000, respectively. All four enzymes lost more than 85% of their activity after 1 hr at temperatures of 50 degrees C or higher in sodium phosphate buffer, pH 7.0. The Km values determined with the most specific substrates for each enzyme were 0.76, 0.44, 3.82, and 8.3 mM for enzymes I, II, III, and IV, respectively. Recent evidence suggests that a significant amount of some small peptides are absorbed intact and hydrolyzed by cytosol peptide hydrolases. Adequate understanding of the function and control of these intracellular enzymes requires knowledge of the characteristics and substrates specificity of individual enzymes. The study described here demonstrates the presence of at least four cytosol peptide hydrolases with distinct substrate specificities. Substrates almost exclusively hydrolyzed by each of three of the enzymes, and therefore suitable for assay of each of these enzymes in the presence of the others, have been identified.", "contents": "Isolation and characterization of four peptide hydrolases from the cytosol of rat intestinal mucosa. The high speed supernatant fluid prepared from rat intestinal mucosa was subjected to ion-exchange chromatography on diethlaminoethyl-cellulose eluted with a linear gradient of sodium chloride (0 to 0.27 M). Assay of eluted fractions for Phe-Gly hydrolase activity revealed four distinct peaks of enzyme activity. These cytosol enzymes have been designated I, II, III, and IV in order of their elution from the column. Examination of the substrate specificity of the four enzymes by use of 20 mM peptide concentrations indicated the most discriminating substrates for the four enzymes were Leu-Gly-Gly, His-Met, Ser-Phe, and leucine amide, respectively. The mean distribution of the recovered peptide hydrolase activities against these substrates among the four enzymes I, II, III, and IV was 96.1, 1.4, 1.7, and 0.8%, respectively, for Leu-Gly-Gly; 0.6, 96.4, 2.4, and 0.6% for His-Met; 0, 0, 95.8, and 4.2% for Ser-Phe; and 20.8, 19.8, 5.6, and 53.8% for leucine amide. Ion-exchange chromatography resulted in increases in specific activity of 19-, 19-, 46-, and 3.5-fold for enzymes I, II, III, and IV, respectively. The activity of all four enzymes, but especially III and IV, were stabilized by the presence of 150 muM dithioerythritol. Activity of each of the four enzymes was decreased 79 to 100% by 1mM ethylenediaminetetraacetate, HgCl2, 1, 10-phenanthroline, or 0.5 mM p-hydroxymercuribenzoate, except that the activity of enzyme I was decreased only 15% by ethylenediaminetetraacetate. No significant activation of the partially purified enzymes occurred in the presence of 500 muM Zn++, Co++, or Mg++. The four enzymes exhibited distinct pH profiles with optima at 7.5, 7.5, 8.5, and 8.0 for enzymes I, II, III, and IV, respectively. Molecular weights of the four enzymes determined by gel filtration on Sephadex G-200 were 58,500, 74,000, 97,500, and 113,000, respectively. All four enzymes lost more than 85% of their activity after 1 hr at temperatures of 50 degrees C or higher in sodium phosphate buffer, pH 7.0. The Km values determined with the most specific substrates for each enzyme were 0.76, 0.44, 3.82, and 8.3 mM for enzymes I, II, III, and IV, respectively. Recent evidence suggests that a significant amount of some small peptides are absorbed intact and hydrolyzed by cytosol peptide hydrolases. Adequate understanding of the function and control of these intracellular enzymes requires knowledge of the characteristics and substrates specificity of individual enzymes. The study described here demonstrates the presence of at least four cytosol peptide hydrolases with distinct substrate specificities. Substrates almost exclusively hydrolyzed by each of three of the enzymes, and therefore suitable for assay of each of these enzymes in the presence of the others, have been identified."}
{"id": "PMID:11150", "title": "[Characteristics of two new mutant forms of erythrocyte glucose-6-phosphate dehydrogenase: \"Kirovograd\" G6PD and \"Zhitomir\" G6PD].", "content": "The paper comprises the description of properties of three mutant forms of glucoso-6-phosphate dehydrogenase characterized according the WHO program. Preparations of the enzymes were isolated from erythrocytes of patients with G6PD deficiency from three unrelated to one another Ashkenasi families coming from the Ukraine and from Byelorussia. Two new variants of G6PD hitherto never described in the literature were discovered. These variants were designated as \"Kirovograd\" and \"Zhitomir\" after the towns the probands came from. The properties of purified enzymes revealed by the methods of the WHO program were as follows: the variant \"Kirovograd\" has a normal electrophoretic mobility in tris and TEB buffers and 98% of the normal in phosphate buffer. KM for G6P is 6,54; KM for NADP--2,19. It is characterized by a reduced thermostability and by an acute peak of activity at pH 8,5. The variant \"Zhitomir\" has 90-98% of the normal electrophoretic mobility in TEB buffer and 78-84% in phosphate buffer. KM for G6P is 5,4-8,3. KM for NADP is 1,4-3,1; with deoxyG6P is 50% and with deaminoNADP is 35%. It is also characterized with a reduced thermostability, while the curve of the dependence of its activity on pH has two peaks. Both variants are perfectly inactive with erythrocytes and thus should be assigned to the second group of the mutants variants of G6PD. The comparison of these variants to other variants encountered in the same national group revealed that they resemble certain quantitative variations.", "contents": "[Characteristics of two new mutant forms of erythrocyte glucose-6-phosphate dehydrogenase: \"Kirovograd\" G6PD and \"Zhitomir\" G6PD]. The paper comprises the description of properties of three mutant forms of glucoso-6-phosphate dehydrogenase characterized according the WHO program. Preparations of the enzymes were isolated from erythrocytes of patients with G6PD deficiency from three unrelated to one another Ashkenasi families coming from the Ukraine and from Byelorussia. Two new variants of G6PD hitherto never described in the literature were discovered. These variants were designated as \"Kirovograd\" and \"Zhitomir\" after the towns the probands came from. The properties of purified enzymes revealed by the methods of the WHO program were as follows: the variant \"Kirovograd\" has a normal electrophoretic mobility in tris and TEB buffers and 98% of the normal in phosphate buffer. KM for G6P is 6,54; KM for NADP--2,19. It is characterized by a reduced thermostability and by an acute peak of activity at pH 8,5. The variant \"Zhitomir\" has 90-98% of the normal electrophoretic mobility in TEB buffer and 78-84% in phosphate buffer. KM for G6P is 5,4-8,3. KM for NADP is 1,4-3,1; with deoxyG6P is 50% and with deaminoNADP is 35%. It is also characterized with a reduced thermostability, while the curve of the dependence of its activity on pH has two peaks. Both variants are perfectly inactive with erythrocytes and thus should be assigned to the second group of the mutants variants of G6PD. The comparison of these variants to other variants encountered in the same national group revealed that they resemble certain quantitative variations."}
{"id": "PMID:11151", "title": "[Influence of the maternal effect on allogenic inhibition of hematopoietic stem cells].", "content": "Bone marrow cells (0,5-10(6)) of female mice of CBA or C57BL strains were injected intravenously to lethally irradiated CBA, C57BL/6, (femaleCBA X maleC57BL/6)F1 and (femaleC57BL/6 X maleCBA)F1 mice. Spleen of recipients as assayed for colony count on the 9th day after bone marrow transplantation by the method of Till and McCullouch. Stem cells of CBA mice demonstrated failure of allogenic inhibition in (CBA X C57BL/6)F1 hybrid mice and formed the same number of colonies as in the spleen of syngenic recipients. The level of allogenic inhibition of CBA stem cells transplanted to (C57BL/6 X X CBA)F1 hybrid mice was 50%. Bone marrow cells of C57BL/6 mice formed colonies in spleen of (CBA X C57BL/6)F1 mice at least in 20 times less than in syngenic combination. In the transplantation of bone marrow from C57BL/6 mice to (C57BL/6 X CBA)F1 hybrid mice the allogenic inhibition was less pronounced (77-85%) as compared with the transfer of cells to (CBA X C57BL/6)F1 hybrid mice (95%). The sex of a recipient did not influence the number of formed colonies. The different level of allogenic inhibition of parental stem cells can not be explained by the effect of linkage with sex as the female of reciprocal hybrid mice have identical structure of sex chromosomes (X(CBA)XC57BL/6). The data obtained indicate that the maternal effect affects allogenic inhibition of stem cells in parent--F1 system. It is possible that the maternal influence may be determined by cytoplasmic factors of inheritance which affect the expressivity of recessive genes Hh, controlling the inheritance of specific haematopoietic cell antigens.", "contents": "[Influence of the maternal effect on allogenic inhibition of hematopoietic stem cells]. Bone marrow cells (0,5-10(6)) of female mice of CBA or C57BL strains were injected intravenously to lethally irradiated CBA, C57BL/6, (femaleCBA X maleC57BL/6)F1 and (femaleC57BL/6 X maleCBA)F1 mice. Spleen of recipients as assayed for colony count on the 9th day after bone marrow transplantation by the method of Till and McCullouch. Stem cells of CBA mice demonstrated failure of allogenic inhibition in (CBA X C57BL/6)F1 hybrid mice and formed the same number of colonies as in the spleen of syngenic recipients. The level of allogenic inhibition of CBA stem cells transplanted to (C57BL/6 X X CBA)F1 hybrid mice was 50%. Bone marrow cells of C57BL/6 mice formed colonies in spleen of (CBA X C57BL/6)F1 mice at least in 20 times less than in syngenic combination. In the transplantation of bone marrow from C57BL/6 mice to (C57BL/6 X CBA)F1 hybrid mice the allogenic inhibition was less pronounced (77-85%) as compared with the transfer of cells to (CBA X C57BL/6)F1 hybrid mice (95%). The sex of a recipient did not influence the number of formed colonies. The different level of allogenic inhibition of parental stem cells can not be explained by the effect of linkage with sex as the female of reciprocal hybrid mice have identical structure of sex chromosomes (X(CBA)XC57BL/6). The data obtained indicate that the maternal effect affects allogenic inhibition of stem cells in parent--F1 system. It is possible that the maternal influence may be determined by cytoplasmic factors of inheritance which affect the expressivity of recessive genes Hh, controlling the inheritance of specific haematopoietic cell antigens."}
{"id": "PMID:11152", "title": "Effect of size of Morris hepatoma 5123D on gamma-glutamyltranspeptidase activity in serum and urine.", "content": "Close correlation between the size of Morris hepatoma 5123D implanted in the hind limb of rat and serum gamm-glutamyltranspeptidase activity was found. The tumour implanted in both hind legs of the rat resulted in about twofold increase of the serum enzyme activity. The growth of the hepatoma resulted also in a significant increase in the enzyme activity in urine of the tumour-bearing rats. After surgical removal of the leg with hepatoma a rapid decrease in the enzyme activity in both the studied body fluids and its subsequent renewed increase associated with formation of pulmonary metastases were observed. Partial hepatectomy and pancreatectomy were without effect on the serum gamma-glutamyltranspeptidase activity.", "contents": "Effect of size of Morris hepatoma 5123D on gamma-glutamyltranspeptidase activity in serum and urine. Close correlation between the size of Morris hepatoma 5123D implanted in the hind limb of rat and serum gamm-glutamyltranspeptidase activity was found. The tumour implanted in both hind legs of the rat resulted in about twofold increase of the serum enzyme activity. The growth of the hepatoma resulted also in a significant increase in the enzyme activity in urine of the tumour-bearing rats. After surgical removal of the leg with hepatoma a rapid decrease in the enzyme activity in both the studied body fluids and its subsequent renewed increase associated with formation of pulmonary metastases were observed. Partial hepatectomy and pancreatectomy were without effect on the serum gamma-glutamyltranspeptidase activity."}
{"id": "PMID:11153", "title": "[Experimental anti-arrhythmic effects of a new beta-adrenergic receptor blocking agent, dl-l-(tert. butylamino)-3-[(2-propinyloxy)phenoxy]2-propanol hydrochloride (dl K\u00f6 1400-Cl)].", "content": "Antiarrhythmic property of a new adrenergic beta-blocking agent, dl-1-(tert.butylamino)-3[(2-propinyloxy) phenoxy]-2-propanol hydrochloride (K\u00f6 1400-Cl) was studied, using 1) ouabain-induced arrhythmia in the guinea pig, 2) aconitine-induced arrhythmia in the rat, 3) arrhythmia induced by two-step ligation of coronary artery (Harris's method) in the dog and 4) halothane-adrenaline arrhythmia in the dog and was compared with those of propranolol, oxprenolol, procainamide and ajmaline. Procainamide and ajmaline produced a marked protective effect against aconitine-induced ventricular extrasystole, but were not so effective against aconitine-induced ventricular fibrillation, while oxprenolol and, to a lesser degree, propranolol were effective against the latter type of aconitine arrhythmias. K\u00f6 1400-Cl proved to be ineffective. All the compounds tested produced a marked protective action against ouabain-arrhythmia. Whereas procainamide was most effective in abolishing the ventricular arrhythmia due to coronary-ligation even on the first postoperative day, K\u00f6 1400-Cl and propranolol were almost ineffective on the first day. Even on the second postoperative day, the antiarrhythmic effects of these two beta-blockers were not remarkable, effective only in 2/4 animals in the case of K\u00f6 1400-Cl and in 2/3 animals in the case of propranolol. On the contrary, all the beta-blockers tested produced a protective action against halothane-adrenaline arrhythmia at much lower doses than against coronary ligation arrhythmia. The potency ratio of K\u00f6 1400-Cl and propranolol was 3 : 1, which paralleled with beta-blocking activity of these compounds.", "contents": "[Experimental anti-arrhythmic effects of a new beta-adrenergic receptor blocking agent, dl-l-(tert. butylamino)-3-[(2-propinyloxy)phenoxy]2-propanol hydrochloride (dl K\u00f6 1400-Cl)]. Antiarrhythmic property of a new adrenergic beta-blocking agent, dl-1-(tert.butylamino)-3[(2-propinyloxy) phenoxy]-2-propanol hydrochloride (K\u00f6 1400-Cl) was studied, using 1) ouabain-induced arrhythmia in the guinea pig, 2) aconitine-induced arrhythmia in the rat, 3) arrhythmia induced by two-step ligation of coronary artery (Harris's method) in the dog and 4) halothane-adrenaline arrhythmia in the dog and was compared with those of propranolol, oxprenolol, procainamide and ajmaline. Procainamide and ajmaline produced a marked protective effect against aconitine-induced ventricular extrasystole, but were not so effective against aconitine-induced ventricular fibrillation, while oxprenolol and, to a lesser degree, propranolol were effective against the latter type of aconitine arrhythmias. K\u00f6 1400-Cl proved to be ineffective. All the compounds tested produced a marked protective action against ouabain-arrhythmia. Whereas procainamide was most effective in abolishing the ventricular arrhythmia due to coronary-ligation even on the first postoperative day, K\u00f6 1400-Cl and propranolol were almost ineffective on the first day. Even on the second postoperative day, the antiarrhythmic effects of these two beta-blockers were not remarkable, effective only in 2/4 animals in the case of K\u00f6 1400-Cl and in 2/3 animals in the case of propranolol. On the contrary, all the beta-blockers tested produced a protective action against halothane-adrenaline arrhythmia at much lower doses than against coronary ligation arrhythmia. The potency ratio of K\u00f6 1400-Cl and propranolol was 3 : 1, which paralleled with beta-blocking activity of these compounds."}
{"id": "PMID:11154", "title": "Exocellular proteases of Serratia marcescens and their toxicity to larvae of Galleria mellonella.", "content": "Out of 18 strains of Serratia marcescens producing exocellular proteases the strain Serratia marcescens CCEB 415 was selected according to preliminary experiments. It could be shown that the train exhibits proteolytic activity reaching up to 10 TU per 1 ml of the culture filtrate in a medium with gelatine and peptone. Two proteolytic enzyme could be demonstrated by means of specific inhibitors EDTA and diisopropyfluorophosphate: metalprotease with optimum activity at pH 7.5 and serine protease with pH optimum of 10.9. The enzymes were purified on Sephadex and DEAE cellulose columns and by means of gel electrophoresis. However, it was not possible to separate them. The optimum temperature for activity of the mixture of the two enzymes was 50degrees C, molecular weight varied around 37000 (according to gel filtration); certain kinetic characteristics of their activity were determined. Excess subtrate (casein) inhibited activity of the enzyme mixture. Toxicity of proteases expressed as LD50 units equals 78 - 10(3) TU per larva of Galleria mellonella.", "contents": "Exocellular proteases of Serratia marcescens and their toxicity to larvae of Galleria mellonella. Out of 18 strains of Serratia marcescens producing exocellular proteases the strain Serratia marcescens CCEB 415 was selected according to preliminary experiments. It could be shown that the train exhibits proteolytic activity reaching up to 10 TU per 1 ml of the culture filtrate in a medium with gelatine and peptone. Two proteolytic enzyme could be demonstrated by means of specific inhibitors EDTA and diisopropyfluorophosphate: metalprotease with optimum activity at pH 7.5 and serine protease with pH optimum of 10.9. The enzymes were purified on Sephadex and DEAE cellulose columns and by means of gel electrophoresis. However, it was not possible to separate them. The optimum temperature for activity of the mixture of the two enzymes was 50degrees C, molecular weight varied around 37000 (according to gel filtration); certain kinetic characteristics of their activity were determined. Excess subtrate (casein) inhibited activity of the enzyme mixture. Toxicity of proteases expressed as LD50 units equals 78 - 10(3) TU per larva of Galleria mellonella."}
{"id": "PMID:11158", "title": "[Teratogenic damages of the male genital organs].", "content": "1. Malformations and functional disturbances of the male genitalia may be caused by teratogens. 2. A short review of the prenatal development points out the possible sites of action. 3. In animals some distinct teratogens produce typical malformation syndromo spermatogenetic cells. Cyproteronacetat, an antiandrogen, suppresses the development of the accessoric genital organs and produces an external feminisation. 4. In man, cryptorchidism, agenesis of the spermatic tracts, anorchia and hypospady are known as non-hereditary malformations. 5. The teratogenic etiology of some disturbances of the spermatogenesis is discussed.", "contents": "[Teratogenic damages of the male genital organs]. 1. Malformations and functional disturbances of the male genitalia may be caused by teratogens. 2. A short review of the prenatal development points out the possible sites of action. 3. In animals some distinct teratogens produce typical malformation syndromo spermatogenetic cells. Cyproteronacetat, an antiandrogen, suppresses the development of the accessoric genital organs and produces an external feminisation. 4. In man, cryptorchidism, agenesis of the spermatic tracts, anorchia and hypospady are known as non-hereditary malformations. 5. The teratogenic etiology of some disturbances of the spermatogenesis is discussed."}
{"id": "PMID:11162", "title": "[Liver function in undisturbed pregnancy].", "content": "In order to evaluate liver function during pregnancy the enzyme activities of GPT, GOT, GLDH, LDH, AP, LAP, gamma-GT and CHE were determined in 272 healthy pregnant women from the 16th week of gestation up to term. The normal range of GPT, GOT, GLDH, LDH, gamma-GT and CHE did not differ significantly from those in non-pregnant women. Increases in AP and LAP are conditioned by placental synthesis. The functional reserves of a healthy liver obviously suffice to compensate for increased demands during pregnancy. Increases in enzyme aktivities during pregnancy are not physiologic - except for increases in AP and LAP.", "contents": "[Liver function in undisturbed pregnancy]. In order to evaluate liver function during pregnancy the enzyme activities of GPT, GOT, GLDH, LDH, AP, LAP, gamma-GT and CHE were determined in 272 healthy pregnant women from the 16th week of gestation up to term. The normal range of GPT, GOT, GLDH, LDH, gamma-GT and CHE did not differ significantly from those in non-pregnant women. Increases in AP and LAP are conditioned by placental synthesis. The functional reserves of a healthy liver obviously suffice to compensate for increased demands during pregnancy. Increases in enzyme aktivities during pregnancy are not physiologic - except for increases in AP and LAP."}
{"id": "PMID:11163", "title": "[Beta receptor blocking agents in psychiatry (author's transl)].", "content": "The effects of beta receptor blocking agents in various psychiatric indications have been investigated during the last decade. The results are summarised and discussed. A final judgement of the value of beta blocking agents within the complete psychopharmacological treatment is, at present, not yet possible. They appear to have a certain therapeutic effect depending on the peripheral beta receptor blockade, at least on functional psycho- and neurovegetative cardial and circulatory disturbances as well as on anxiety states, neurotic and those caused by stress, both of these presenting primarily somatic symptoms. In other cases the results, as they now stand, present some very interesting features for further investigation.", "contents": "[Beta receptor blocking agents in psychiatry (author's transl)]. The effects of beta receptor blocking agents in various psychiatric indications have been investigated during the last decade. The results are summarised and discussed. A final judgement of the value of beta blocking agents within the complete psychopharmacological treatment is, at present, not yet possible. They appear to have a certain therapeutic effect depending on the peripheral beta receptor blockade, at least on functional psycho- and neurovegetative cardial and circulatory disturbances as well as on anxiety states, neurotic and those caused by stress, both of these presenting primarily somatic symptoms. In other cases the results, as they now stand, present some very interesting features for further investigation."}
{"id": "PMID:11164", "title": "[A sensitive fluorometric determination of catechol methyltransferase activity (author's transl)].", "content": "A method for the determination of catechol-methyltransferase activity is described, based on the measurement of fluorometric intensity of 7-hydroxy-6-methoxycoumarin (scopoletin), enzymatically produced by dihydroxycoumarin in the presence of the methyl donor S-adenosylmethionine.", "contents": "[A sensitive fluorometric determination of catechol methyltransferase activity (author's transl)]. A method for the determination of catechol-methyltransferase activity is described, based on the measurement of fluorometric intensity of 7-hydroxy-6-methoxycoumarin (scopoletin), enzymatically produced by dihydroxycoumarin in the presence of the methyl donor S-adenosylmethionine."}
{"id": "PMID:11165", "title": "[Detection of multiple molecular forms of the gamma-glutamyltransferase by concanavalin A affinity chromatography (author's transl)].", "content": "The separation of several forms of gamma-glutamyl-transferase was achieved by using concanavalin A-Sepharose columns. The enzyme of the adult liver was bound totally to the lectin, whereas only 5% of the kidney enzyme and 50% of the pancreas gamma-glutamyltransferase was adsorbed by concanavalin A. Due to a higher content of N-acetylneuraminic acid, the enzyme of the fetal liver does not show any affinity to concanavalin A. Within 8 days after birth the N-acetylneuraminic acid-rich fetal gamma-glutamyltransferase is substituted by the adult form.", "contents": "[Detection of multiple molecular forms of the gamma-glutamyltransferase by concanavalin A affinity chromatography (author's transl)]. The separation of several forms of gamma-glutamyl-transferase was achieved by using concanavalin A-Sepharose columns. The enzyme of the adult liver was bound totally to the lectin, whereas only 5% of the kidney enzyme and 50% of the pancreas gamma-glutamyltransferase was adsorbed by concanavalin A. Due to a higher content of N-acetylneuraminic acid, the enzyme of the fetal liver does not show any affinity to concanavalin A. Within 8 days after birth the N-acetylneuraminic acid-rich fetal gamma-glutamyltransferase is substituted by the adult form."}
{"id": "PMID:11166", "title": "[Isoelectric focusing of complex protein mixtures in the nanogram range in microgels (author's transl)].", "content": "A method is described for isolectric focusing of complex protein mixtures in 2, 5 or 10 mul capillaries. For one separation only 15- 50 ng of a protein mixture is needed. Isoelectric focusing is finished after 10 min, staining takes 20 min and destaining approximately 30 min. Using defined mixtures of Servalyt from different pH ranges, isoelectric focusing can be adapted to the protein sample to be fractionated. Protein peaks separated by isoelectric focusing can be electrophoretically eluted and for further analysis refractionated directly in a microgradient gel. The resolution power of microisoelectric focusing is as good as that of the wellknown macroprocedure, as is demonstrated by isoelectric focusing of the water soluble proteins from cerebellum and heart, of rat and human serum and of a human oncocytoma of the thyroid gland.", "contents": "[Isoelectric focusing of complex protein mixtures in the nanogram range in microgels (author's transl)]. A method is described for isolectric focusing of complex protein mixtures in 2, 5 or 10 mul capillaries. For one separation only 15- 50 ng of a protein mixture is needed. Isoelectric focusing is finished after 10 min, staining takes 20 min and destaining approximately 30 min. Using defined mixtures of Servalyt from different pH ranges, isoelectric focusing can be adapted to the protein sample to be fractionated. Protein peaks separated by isoelectric focusing can be electrophoretically eluted and for further analysis refractionated directly in a microgradient gel. The resolution power of microisoelectric focusing is as good as that of the wellknown macroprocedure, as is demonstrated by isoelectric focusing of the water soluble proteins from cerebellum and heart, of rat and human serum and of a human oncocytoma of the thyroid gland."}
{"id": "PMID:11167", "title": "Activation of snail (Helix pomatia) nervous tissue tyrosine monooxygenase by calcium in vitro.", "content": "Addition of calcium chloride to soluble preparations of tyrosine monooxygenase from snail brain appears to produce an activation of the enzyme when assayed with subsaturating concentrations of the pteridine cofactor 6 MPH4 (2-amino-4-hydroxy-6-methyltetrahydropteridine). While some increase in the activity occurs with calcium chloride at a concentration of 0.01 mM, activation is increased by about 100% at 1mM and reaches a maximum at 5mM (144%) where it remains more or less constant up to 10mM. Barium chloride also produces an activating effect although it is much less pronounced while magnesium chloride is without effect. EGTA has no direct effect on the enzyme but antagonises the activation produced by calcium chloride. The activation of tyrosine monooxygenase by calcium is reflected in changes in the kinetic properties of the enzyme, decreasing the Km from 43 muM to 19 muM for tyrosine and from 670muM to 230muM for the pteridine cofactor. No change was observed with V values for either tyrosine or pteridine cofactor. It is suggested that calcium, which enters the nerve terminal during nerve stimulation, regulates the transmitter dopamine by activating the rate-limiting enzyme tyrosine monooxygenase.", "contents": "Activation of snail (Helix pomatia) nervous tissue tyrosine monooxygenase by calcium in vitro. Addition of calcium chloride to soluble preparations of tyrosine monooxygenase from snail brain appears to produce an activation of the enzyme when assayed with subsaturating concentrations of the pteridine cofactor 6 MPH4 (2-amino-4-hydroxy-6-methyltetrahydropteridine). While some increase in the activity occurs with calcium chloride at a concentration of 0.01 mM, activation is increased by about 100% at 1mM and reaches a maximum at 5mM (144%) where it remains more or less constant up to 10mM. Barium chloride also produces an activating effect although it is much less pronounced while magnesium chloride is without effect. EGTA has no direct effect on the enzyme but antagonises the activation produced by calcium chloride. The activation of tyrosine monooxygenase by calcium is reflected in changes in the kinetic properties of the enzyme, decreasing the Km from 43 muM to 19 muM for tyrosine and from 670muM to 230muM for the pteridine cofactor. No change was observed with V values for either tyrosine or pteridine cofactor. It is suggested that calcium, which enters the nerve terminal during nerve stimulation, regulates the transmitter dopamine by activating the rate-limiting enzyme tyrosine monooxygenase."}
{"id": "PMID:11168", "title": "Extrinsic signals for monitoring the association reaction of proteins as introduced by fluorescent and non-fluorescent labels.", "content": "Two known dansyl labels (I, II) and 5-[2-(iodoacetamido)ethylamino]-1-naphthalene-sulfonic acid (III) and three new azo-dyes (IV - VI) were covalently attached to alpha-chymotrypsin and to basic pancreatic trypsin inhibitor by four different reactive groups. In order to protect the contact region of the proteins the complex of the two proteins was labeled. Advantage was taken of the fact that a group which is buried in the complex reacts about (see article) times slower than a group which is always exposed (K = dissociation equilibrium constant, [C] = concentration of the complex). The complex was dissociated at pH 3 and the labeled proteins were isolated by column chromatography. They were fully active. The dansyl label was immobilized when introduced by dansyl chloride but highly mobile when attached via the longer imidoester group (II). Changes of absorption and of fluorescence which occur when differently labeled reaction partners recombine were studied. Changes in absorption (up to 18%) were mainly due to interactions of the label of one protein with the other protein. Fluorescence changes of up to 480% could be obtained. They were interpreted in terms of a F\u00f6rster type energy transfer between donor and acceptor labels and changes of absorption and quantum yield due to interactions of the labels with the proteins. The kinetic constants of complex formation are not seriously altered by the labels (B\u00f6sterling, B & Engel, J. (1976) this J. 357, 1297-1307, succeeding). It is concluded that the labeling technique may be of general value for kinetic and equilibrium studies of protein associations.", "contents": "Extrinsic signals for monitoring the association reaction of proteins as introduced by fluorescent and non-fluorescent labels. Two known dansyl labels (I, II) and 5-[2-(iodoacetamido)ethylamino]-1-naphthalene-sulfonic acid (III) and three new azo-dyes (IV - VI) were covalently attached to alpha-chymotrypsin and to basic pancreatic trypsin inhibitor by four different reactive groups. In order to protect the contact region of the proteins the complex of the two proteins was labeled. Advantage was taken of the fact that a group which is buried in the complex reacts about (see article) times slower than a group which is always exposed (K = dissociation equilibrium constant, [C] = concentration of the complex). The complex was dissociated at pH 3 and the labeled proteins were isolated by column chromatography. They were fully active. The dansyl label was immobilized when introduced by dansyl chloride but highly mobile when attached via the longer imidoester group (II). Changes of absorption and of fluorescence which occur when differently labeled reaction partners recombine were studied. Changes in absorption (up to 18%) were mainly due to interactions of the label of one protein with the other protein. Fluorescence changes of up to 480% could be obtained. They were interpreted in terms of a F\u00f6rster type energy transfer between donor and acceptor labels and changes of absorption and quantum yield due to interactions of the labels with the proteins. The kinetic constants of complex formation are not seriously altered by the labels (B\u00f6sterling, B & Engel, J. (1976) this J. 357, 1297-1307, succeeding). It is concluded that the labeling technique may be of general value for kinetic and equilibrium studies of protein associations."}
{"id": "PMID:11169", "title": "Influence of various fluorescent and non-fluorescent labels on the kinetics of the complex formation of alpha-chymotrypsin with basic pancreatic trypsin inhibitor (Kunitz).", "content": "The association of alpha-chymotrypsin with basic pancreatic trypsin inhibitor was studied using extrinsic signals produced by fluorescent and nonfluorescent labels. The reactive dyes were covalently bound to the proteins in the complexed state, in which the binding region was protected. The signals were sufficiently large to measure the complex formation at protein concentrations of 10(-9)M by fluorescence and down to 10(-6)M by absorption. Therefore, the association and dissociation could be followed over a broad range of concentration. Good correspondence was observed between data which were obtained with different labels and with published values for the unlabeled proteins. Existing differences could be explained by different buffer conditions used by the different authors. Also the pH dependence of the dissociation rate constants was essentially unaltered by the introduction of the labels. The large signals allowed a direct measurement of the equilibrium constants of dissociation, even at high pH, at which they are in the range of 10(-8)M. The experimentally determined binding constants were in agreement with those calculated from the rate constants. The temperature dependence of the binding constants revealed a small positive and pH-dependent enthalpy change [deltaHo = 4.0 kcal/mol (16.7 kJ) at H 7.0[. The results prove that the labeling can be performed in such a way that the equilibrium and kinetic parameters of the system studied are not significantly influenced.", "contents": "Influence of various fluorescent and non-fluorescent labels on the kinetics of the complex formation of alpha-chymotrypsin with basic pancreatic trypsin inhibitor (Kunitz). The association of alpha-chymotrypsin with basic pancreatic trypsin inhibitor was studied using extrinsic signals produced by fluorescent and nonfluorescent labels. The reactive dyes were covalently bound to the proteins in the complexed state, in which the binding region was protected. The signals were sufficiently large to measure the complex formation at protein concentrations of 10(-9)M by fluorescence and down to 10(-6)M by absorption. Therefore, the association and dissociation could be followed over a broad range of concentration. Good correspondence was observed between data which were obtained with different labels and with published values for the unlabeled proteins. Existing differences could be explained by different buffer conditions used by the different authors. Also the pH dependence of the dissociation rate constants was essentially unaltered by the introduction of the labels. The large signals allowed a direct measurement of the equilibrium constants of dissociation, even at high pH, at which they are in the range of 10(-8)M. The experimentally determined binding constants were in agreement with those calculated from the rate constants. The temperature dependence of the binding constants revealed a small positive and pH-dependent enthalpy change [deltaHo = 4.0 kcal/mol (16.7 kJ) at H 7.0[. The results prove that the labeling can be performed in such a way that the equilibrium and kinetic parameters of the system studied are not significantly influenced."}
{"id": "PMID:11177", "title": "Rat liver cells in culture: effect of storage, long-term culture, and transformation on some enzyme levels.", "content": "Aryl hydrocarbon hydroxylase (AHH) and tyrosine aminotransferase (TAT) activities were determined in rat liver cell lines after frozen storage, long-term culture, and transformation in vitro. Levels of AHH activity after 17 months in frozen storage were comparable to levels prior to freezing. During long-term culture the AHH levels of the cell lines tended to decrease. Transformed lines had variable levels of AHH activity. Cell lines retained measurable TAT activity following long-term culture and frozen storage. TAT activity of transformed cells was comparable to that of normal lines. Prolonged frozen storage did not induce transformation up to one year.", "contents": "Rat liver cells in culture: effect of storage, long-term culture, and transformation on some enzyme levels. Aryl hydrocarbon hydroxylase (AHH) and tyrosine aminotransferase (TAT) activities were determined in rat liver cell lines after frozen storage, long-term culture, and transformation in vitro. Levels of AHH activity after 17 months in frozen storage were comparable to levels prior to freezing. During long-term culture the AHH levels of the cell lines tended to decrease. Transformed lines had variable levels of AHH activity. Cell lines retained measurable TAT activity following long-term culture and frozen storage. TAT activity of transformed cells was comparable to that of normal lines. Prolonged frozen storage did not induce transformation up to one year."}
{"id": "PMID:11178", "title": "Synthesis of alpha subunit of human chorionic gonadotrophin by presumptive HeLa cells.", "content": "Several cell lines, originally thought to be derived from a human placenta at term but possibly HeLa-contaminated, have been studied. These cells secrete a protein indistinguishable immunochemically from the alpha subunit of chorionic gonadotropin but not the beta subunit of chorionic gonadotropin or placental lactogen. Complete chorionic gonadotropin was detected but amounted to less than 1% of the level of the alpha subunit. The cells also produce an alkaline phosphatase similar to placental alkaline phosphatase in immunochemical, gel-electrophoretic, and heat-denaturation properties. They induce tumor growth when inoculated into nude mice. These cells are aneuploid and have a model chromosome number of 66. The common HeLa karyologic markers, designated 1, 2, and 3, and A-type glucose-6-phosphate dehydrogenase are present in these cells. HeLa cells have not previously been shown to secrete the alpha subunit of hCG.", "contents": "Synthesis of alpha subunit of human chorionic gonadotrophin by presumptive HeLa cells. Several cell lines, originally thought to be derived from a human placenta at term but possibly HeLa-contaminated, have been studied. These cells secrete a protein indistinguishable immunochemically from the alpha subunit of chorionic gonadotropin but not the beta subunit of chorionic gonadotropin or placental lactogen. Complete chorionic gonadotropin was detected but amounted to less than 1% of the level of the alpha subunit. The cells also produce an alkaline phosphatase similar to placental alkaline phosphatase in immunochemical, gel-electrophoretic, and heat-denaturation properties. They induce tumor growth when inoculated into nude mice. These cells are aneuploid and have a model chromosome number of 66. The common HeLa karyologic markers, designated 1, 2, and 3, and A-type glucose-6-phosphate dehydrogenase are present in these cells. HeLa cells have not previously been shown to secrete the alpha subunit of hCG."}
{"id": "PMID:11179", "title": "[Approach to a practical method for screening and identifying microorganism genera from urine (author's transl)].", "content": "In this study the author reported upon a practical new system for screening and identifying the microbial agents causing urinary tract infections. This system is composed of a combination of 3 screening procedures (pH-value + nitrite-test + catalase-test) and 8 selective culture media for the purpose of genus identification within 24 hours (Uripret-G). A total of 130 cultures was investigated. The employed microorganisms were mainly recovered from urine samples. They included the following species: Candida albicans, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus inconstans, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris, Serratia liquefaciens, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis and Streptococcus faecium. Employing coded cultures not only monoinfections but also multiinfections in urine samples were simulated. Under the circumstances of investigation it was possible with the help of the new system to reidentify the genera of all but two of the 130 employed microorganisms.", "contents": "[Approach to a practical method for screening and identifying microorganism genera from urine (author's transl)]. In this study the author reported upon a practical new system for screening and identifying the microbial agents causing urinary tract infections. This system is composed of a combination of 3 screening procedures (pH-value + nitrite-test + catalase-test) and 8 selective culture media for the purpose of genus identification within 24 hours (Uripret-G). A total of 130 cultures was investigated. The employed microorganisms were mainly recovered from urine samples. They included the following species: Candida albicans, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus inconstans, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris, Serratia liquefaciens, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis and Streptococcus faecium. Employing coded cultures not only monoinfections but also multiinfections in urine samples were simulated. Under the circumstances of investigation it was possible with the help of the new system to reidentify the genera of all but two of the 130 employed microorganisms."}
{"id": "PMID:11180", "title": "Slow reacting substance as a preformed mediator from human lung.", "content": "Homogenates from human lung contained a preformed slow reacting substance (pSRS). The pattern of contraction on the guinea-pig ileum by pSRS was indistinguishable from that of SRS-A. The activity of pSRS could not be attributed to the presence of K+, Na+, Ca2+ and Mg2+ ions, or any prostaglandin including PGF2 or its 15-oxo derivative. As with SRS-A, pSRS could be absorbed onto Amberlite XAD-2 and silicic acid. Both were eluted from the former with 80 per cent ethanol and from the latter with a mixture of ethanol, ammonia and water. Both pSRS and SRS-A were resistant to the action of NaOH whereas their activities were destroyed by boiling in HCl. Arylsulphatase II B destroyed the activities of both pSRS and SRS-A. An antagonist of SRS-A, FPL55712, inhibited the action of pSRS at comparable concentrations to that of SRS-A. These experiments suggest that pSRS and SRS-A are identical. Thus SRS joins histamine and ECF-A as a preformed mediator. Although SRS was present in a preformed state the amount of material extractable was more than doubled by the anaphylactic reaction. The extraction of slow reacting substance from human lung without apparent requirement for antigen or antibody points to a possible role of this mediator in inflammatory reactions evoked by mechanisms independent of IgE and other tissue-sensitizing antibodies.", "contents": "Slow reacting substance as a preformed mediator from human lung. Homogenates from human lung contained a preformed slow reacting substance (pSRS). The pattern of contraction on the guinea-pig ileum by pSRS was indistinguishable from that of SRS-A. The activity of pSRS could not be attributed to the presence of K+, Na+, Ca2+ and Mg2+ ions, or any prostaglandin including PGF2 or its 15-oxo derivative. As with SRS-A, pSRS could be absorbed onto Amberlite XAD-2 and silicic acid. Both were eluted from the former with 80 per cent ethanol and from the latter with a mixture of ethanol, ammonia and water. Both pSRS and SRS-A were resistant to the action of NaOH whereas their activities were destroyed by boiling in HCl. Arylsulphatase II B destroyed the activities of both pSRS and SRS-A. An antagonist of SRS-A, FPL55712, inhibited the action of pSRS at comparable concentrations to that of SRS-A. These experiments suggest that pSRS and SRS-A are identical. Thus SRS joins histamine and ECF-A as a preformed mediator. Although SRS was present in a preformed state the amount of material extractable was more than doubled by the anaphylactic reaction. The extraction of slow reacting substance from human lung without apparent requirement for antigen or antibody points to a possible role of this mediator in inflammatory reactions evoked by mechanisms independent of IgE and other tissue-sensitizing antibodies."}
{"id": "PMID:11181", "title": "Analysis of immunosuppression generated by the graft-versus-host reaction. II. Characterization of the suppression cell and its mechanism of action.", "content": "Spleen cells from (CBA X C57/BL) F1 mice undergoing graft-versus-host (GVH) reaction induced by injection of parental cells 7-14 days previously are capable of suppressing an immune response by normal or primed F1 spleen cells to chicken erythrocytes and levan in vivo and sheep erythrocytes in vitro. The cells in these GVH spleens which were responsible for the suppression were sensitive to treatment with anti-0 serum, resistant to 900 rad irradiation in vivo and not retained by anti-immunoglobulin columns. Suppressor activity in vitro was present only in the non-adherent fraction of these GVH cell suspensions. Furthermore, the T-cell fraction, purified by affinity chromatography, suppressed the in vitro response of macrophage-depleted normal F1 cells to DNP-levan. Collectively, these observations imply that suppressor T cells generated by GVH reaction can affect B-cell functions directly without intermediary macrophage participation. Spleen cells from (CBA X C57/BL) F1 mice undergoing GVH reaction induced by C57/BL cells were depleted of their F1 content by treatment with anti-CBA alloantiserum. The suppressive activity of the residual donor component was still expressed against other F1 cells (AKR X C57/BL) which were H-2 compatible with the original host, but not against H-2-incompatible cells (DBA/1 X C57/BL) F1. However, the latter were suppressed in the presence of (CBA X C57/BL) F1 cells. Thus, interaction of donor T cells with F1 target cells containing those H-2 antigens towards which they are sensitized is mandatory for the subsequent manifestation of immunosuppressive activity. GVH cells suppressed the response of primed F1 cells in double Marbrook chambers when the two populations were separated were by a cell-impermeable membrane, provided the GVH suspension contained F1 cells to which donor T cells were sensitized. This suggests that soluble factors are involved in the mechanism of GVH-induced immunosuppression.", "contents": "Analysis of immunosuppression generated by the graft-versus-host reaction. II. Characterization of the suppression cell and its mechanism of action. Spleen cells from (CBA X C57/BL) F1 mice undergoing graft-versus-host (GVH) reaction induced by injection of parental cells 7-14 days previously are capable of suppressing an immune response by normal or primed F1 spleen cells to chicken erythrocytes and levan in vivo and sheep erythrocytes in vitro. The cells in these GVH spleens which were responsible for the suppression were sensitive to treatment with anti-0 serum, resistant to 900 rad irradiation in vivo and not retained by anti-immunoglobulin columns. Suppressor activity in vitro was present only in the non-adherent fraction of these GVH cell suspensions. Furthermore, the T-cell fraction, purified by affinity chromatography, suppressed the in vitro response of macrophage-depleted normal F1 cells to DNP-levan. Collectively, these observations imply that suppressor T cells generated by GVH reaction can affect B-cell functions directly without intermediary macrophage participation. Spleen cells from (CBA X C57/BL) F1 mice undergoing GVH reaction induced by C57/BL cells were depleted of their F1 content by treatment with anti-CBA alloantiserum. The suppressive activity of the residual donor component was still expressed against other F1 cells (AKR X C57/BL) which were H-2 compatible with the original host, but not against H-2-incompatible cells (DBA/1 X C57/BL) F1. However, the latter were suppressed in the presence of (CBA X C57/BL) F1 cells. Thus, interaction of donor T cells with F1 target cells containing those H-2 antigens towards which they are sensitized is mandatory for the subsequent manifestation of immunosuppressive activity. GVH cells suppressed the response of primed F1 cells in double Marbrook chambers when the two populations were separated were by a cell-impermeable membrane, provided the GVH suspension contained F1 cells to which donor T cells were sensitized. This suggests that soluble factors are involved in the mechanism of GVH-induced immunosuppression."}
{"id": "PMID:11187", "title": "Large-scale purification and characterization of the exotoxin of Pseudomonas aeruginosa.", "content": "The exotoxin (PE) of Pseudomonas aeruginosa was purified from 50-liter cultures by a simple three-step procedure, yielding 135 mg of essentially homogeneous protein. In Ouchterlony gel diffusion, PE produces a single line which does not interact with a diphtheria toxin-antitoxin precipitin line. The protein has a molecular weight of 66,000, an isoelectric point of 5.1, N-terminal arginine, and four disulfide bridges. The amino acid composition shows no apparent similarity to that of diphtheria toxin. The median lethal dose of this PE preparation in mice weighing 20 g is 0.1 mug. The median lethal dose in 350-g rats is 20 mug. The cytotoxicity of PE for mouse L929 fibroblasts is completely neutralized by small amounts of specific pony antitoxin. The exotoxin possesses adenosine diphosphate-ribosylation activity. Both cytotoxic and adenosine diphosphate-ribosylation activities are shown to be properties of the intact 66,000-dalton protein.", "contents": "Large-scale purification and characterization of the exotoxin of Pseudomonas aeruginosa. The exotoxin (PE) of Pseudomonas aeruginosa was purified from 50-liter cultures by a simple three-step procedure, yielding 135 mg of essentially homogeneous protein. In Ouchterlony gel diffusion, PE produces a single line which does not interact with a diphtheria toxin-antitoxin precipitin line. The protein has a molecular weight of 66,000, an isoelectric point of 5.1, N-terminal arginine, and four disulfide bridges. The amino acid composition shows no apparent similarity to that of diphtheria toxin. The median lethal dose of this PE preparation in mice weighing 20 g is 0.1 mug. The median lethal dose in 350-g rats is 20 mug. The cytotoxicity of PE for mouse L929 fibroblasts is completely neutralized by small amounts of specific pony antitoxin. The exotoxin possesses adenosine diphosphate-ribosylation activity. Both cytotoxic and adenosine diphosphate-ribosylation activities are shown to be properties of the intact 66,000-dalton protein."}
{"id": "PMID:11188", "title": "Serum bactericidal activity in the horseshoe crab, Limulus polyphemus.", "content": "Serum from the horseshoe crab, Limulus polyphemus, was examined for bactericidal activity against five species of bacteria. Greatest activity was found against Pseudomonas putida and Flavobacterium sp.; with the former, serum dilutions as high as 1:20 were capable of reducing viable counts by 50% within 2 h. Bactericidal activity of a significantly lesser magnitude was demonstrated against Serratia marcesencs and Salmonella minnesota. No killing was seen when the lobster pathogen Aerococcus viridans (formerly Gaffkya homari) was used. The cidal activity against Flavobacterium sp. remained relatively consistent for 6 months.", "contents": "Serum bactericidal activity in the horseshoe crab, Limulus polyphemus. Serum from the horseshoe crab, Limulus polyphemus, was examined for bactericidal activity against five species of bacteria. Greatest activity was found against Pseudomonas putida and Flavobacterium sp.; with the former, serum dilutions as high as 1:20 were capable of reducing viable counts by 50% within 2 h. Bactericidal activity of a significantly lesser magnitude was demonstrated against Serratia marcesencs and Salmonella minnesota. No killing was seen when the lobster pathogen Aerococcus viridans (formerly Gaffkya homari) was used. The cidal activity against Flavobacterium sp. remained relatively consistent for 6 months."}
{"id": "PMID:11189", "title": "Immunity to Mycobacterium leprae infections in mice stimulated by M. leprae, BCG, and graft-versus-host reactions.", "content": "Infections of mice with Mycobacterium leprae in one rear foot pad immunized them against a second infection in the other rear foot pad. Purified bacilli harvested from the first infection also produced immuniy when injection into the foot pads of previously uninfected mice. Injections of BCG afforded similar protection, but had no adjuvant effect on M. leprae. M. duvali, a cultivable mycobacterium that is reported to be more closely related antigenically to M. leprae than BCG is, provided much less protection against M. leprae challenge than BCG did. Moreover, when M. duvali was mixed with BCG, it was not any more effective than BCG alone. Graft-versus-host reactions, induced by injections of parental spleen cells into F1 hybrids, provided no protection against M. tuberculosis and M. marinum challenge. They gave moderate protection against M. leprae in one experiment but not in another with a different schedule. Allogenic spleen cells had a protective effect when injected locally into the infected foot pad. The effect produced by these injections of spleen cells was a delay in the appearance of bacterial growth; however, there was no decrease in the rate of logarithmic growth when it did appear and no reduction in the eventual plateau level.", "contents": "Immunity to Mycobacterium leprae infections in mice stimulated by M. leprae, BCG, and graft-versus-host reactions. Infections of mice with Mycobacterium leprae in one rear foot pad immunized them against a second infection in the other rear foot pad. Purified bacilli harvested from the first infection also produced immuniy when injection into the foot pads of previously uninfected mice. Injections of BCG afforded similar protection, but had no adjuvant effect on M. leprae. M. duvali, a cultivable mycobacterium that is reported to be more closely related antigenically to M. leprae than BCG is, provided much less protection against M. leprae challenge than BCG did. Moreover, when M. duvali was mixed with BCG, it was not any more effective than BCG alone. Graft-versus-host reactions, induced by injections of parental spleen cells into F1 hybrids, provided no protection against M. tuberculosis and M. marinum challenge. They gave moderate protection against M. leprae in one experiment but not in another with a different schedule. Allogenic spleen cells had a protective effect when injected locally into the infected foot pad. The effect produced by these injections of spleen cells was a delay in the appearance of bacterial growth; however, there was no decrease in the rate of logarithmic growth when it did appear and no reduction in the eventual plateau level."}
{"id": "PMID:11191", "title": "The distribution of hepatitis B surface antigen in Africa and the tropics: report of a population study in Nigeria.", "content": "This preliminary study was designed to examine the distribution of hepatitis B surface antigen (HBsAg) in two contrasting groups in an urban area situated in the tropical forest belt. The sample from the traditional area represents a population of low socio-economic status, living in the central slum areas of the city, and the sample from the peripheral area represents a population of high socio-economic status living in clean modern estates. The prevalence rate of HBsAg by complement fixation (CF) was 12-6 per cent in both areas. There was no statistically significant difference between the two groups with respect to prevalence of the antigen. When both groups were combined, no significant relationship was found between the presence of the antigen and sex, age, marital status, level of education, occupation, income, and a presumed exposure to the antigen from injections, dental treatment, blood tests, surgical operations, blood donations, tribal, (medicinal), tattoo and cosmetic marking, insanitary disposal of faeces, doubtful sources of water supply, and exposure to mosquitoes. No association with genotype was found.", "contents": "The distribution of hepatitis B surface antigen in Africa and the tropics: report of a population study in Nigeria. This preliminary study was designed to examine the distribution of hepatitis B surface antigen (HBsAg) in two contrasting groups in an urban area situated in the tropical forest belt. The sample from the traditional area represents a population of low socio-economic status, living in the central slum areas of the city, and the sample from the peripheral area represents a population of high socio-economic status living in clean modern estates. The prevalence rate of HBsAg by complement fixation (CF) was 12-6 per cent in both areas. There was no statistically significant difference between the two groups with respect to prevalence of the antigen. When both groups were combined, no significant relationship was found between the presence of the antigen and sex, age, marital status, level of education, occupation, income, and a presumed exposure to the antigen from injections, dental treatment, blood tests, surgical operations, blood donations, tribal, (medicinal), tattoo and cosmetic marking, insanitary disposal of faeces, doubtful sources of water supply, and exposure to mosquitoes. No association with genotype was found."}
{"id": "PMID:11192", "title": "Thermal fragmentation of Escherichia coli beta-galactosidase. Isolation and characterization of an alpha-complementing and two non-complementing polypeptide fractions.", "content": "Carboxymethylated Escherichia coli beta-galactosidase EC 3.2.1.23 could be broken to polypeptides of fairly uniform size (average molecular weight about 22,000 daltons) by heating for less than or equal to 8 h at 100 degrees C and pH 7.5 IN 8 M-urea. Using phosphocellulose chromatography in NaCl-urea gradients, the resulting polypeptide mixture could be resolved in three fractions essentially homogeneous by disc gel electrophoresis in urea at several pH values, and by isoelectric focusing. One of these fractions was active as alpha-donor in in vitro complementation of beta-galactosidase activity with Escherichia coli mutant M15; this activity was largely retained after CNBr cleavage. All three fractions carried arginine as carboxyl-terminal amino acid. No significant amount of any specific amino could be detected in NH2-terminal position.", "contents": "Thermal fragmentation of Escherichia coli beta-galactosidase. Isolation and characterization of an alpha-complementing and two non-complementing polypeptide fractions. Carboxymethylated Escherichia coli beta-galactosidase EC 3.2.1.23 could be broken to polypeptides of fairly uniform size (average molecular weight about 22,000 daltons) by heating for less than or equal to 8 h at 100 degrees C and pH 7.5 IN 8 M-urea. Using phosphocellulose chromatography in NaCl-urea gradients, the resulting polypeptide mixture could be resolved in three fractions essentially homogeneous by disc gel electrophoresis in urea at several pH values, and by isoelectric focusing. One of these fractions was active as alpha-donor in in vitro complementation of beta-galactosidase activity with Escherichia coli mutant M15; this activity was largely retained after CNBr cleavage. All three fractions carried arginine as carboxyl-terminal amino acid. No significant amount of any specific amino could be detected in NH2-terminal position."}
{"id": "PMID:11193", "title": "The effects of hallucinogens on blind monkeys.", "content": "Two blind monkeys were studied with an observational profile that was previously shown to distinguish the effects of hallucinogens from those of other classes of drugs. Lysergic acid diethylamide and dimethyltryptamine could be distinguished from saline, chlorpromazine, d-amphetamine sulfate, and bromo-lysergic acid diethylamide by the increased frequency of spasms, stereotypy, bump, and tracking. The hallucinogens also produced dramatic increases in exploration and related behaviors normally seen only in response to real visual or auditory stimuli. These behaviors are discussed in terms of their similarity to behaviors observed with sighted monkeys in light and dark environments.", "contents": "The effects of hallucinogens on blind monkeys. Two blind monkeys were studied with an observational profile that was previously shown to distinguish the effects of hallucinogens from those of other classes of drugs. Lysergic acid diethylamide and dimethyltryptamine could be distinguished from saline, chlorpromazine, d-amphetamine sulfate, and bromo-lysergic acid diethylamide by the increased frequency of spasms, stereotypy, bump, and tracking. The hallucinogens also produced dramatic increases in exploration and related behaviors normally seen only in response to real visual or auditory stimuli. These behaviors are discussed in terms of their similarity to behaviors observed with sighted monkeys in light and dark environments."}
{"id": "PMID:11194", "title": "A review of psychotropic medications and the glaucomas.", "content": "Four general groups of psychotropic drugs are examined with respect to possible adverse effects upon intraocular pressure. After a brief discussion of the various mechanisms of the glaucomas, both general and specific information is provided and discussed concerning antipsychotic, antidepressant, antiparkinsonian and antianxiety preparations of a variety of chemical structures and utilities. The consensus of the authors is that with certain basic safeguards virtually all of the medications studied are acceptably safe to prescribe even in patients with diagnosed glaucoma.", "contents": "A review of psychotropic medications and the glaucomas. Four general groups of psychotropic drugs are examined with respect to possible adverse effects upon intraocular pressure. After a brief discussion of the various mechanisms of the glaucomas, both general and specific information is provided and discussed concerning antipsychotic, antidepressant, antiparkinsonian and antianxiety preparations of a variety of chemical structures and utilities. The consensus of the authors is that with certain basic safeguards virtually all of the medications studied are acceptably safe to prescribe even in patients with diagnosed glaucoma."}
{"id": "PMID:11197", "title": "[Prolactin in male reproduction].", "content": "Prolactin (PRL), a peptide hormon from the hypophysis, becomes more interesting, since it can be determined by radioimmunassays. The release of prolactin is controlled by two not yet identified factors, the prolactin-releasing-factor and the prolactin-inhibiting-factor. The latter predominantes. Many pharmacological substances can alter the release. The normal serum levels in the man are 6-13 ng/ml. Prolactin affects many organs, f.e. kidney, mamma, ovary, testis, hepar and skin. For clinical tests the raise in the serum levels after TSH or chlorpromacin and the drop after application of 2-brom-alpha-ergocryptin is used. Increased serum levels are found in patients with prolactin-producing tumors. In the male this is followed by disturbances of the sexual potency. Relations between prolactin and male infertility of gynecomastia are not yet known.", "contents": "[Prolactin in male reproduction]. Prolactin (PRL), a peptide hormon from the hypophysis, becomes more interesting, since it can be determined by radioimmunassays. The release of prolactin is controlled by two not yet identified factors, the prolactin-releasing-factor and the prolactin-inhibiting-factor. The latter predominantes. Many pharmacological substances can alter the release. The normal serum levels in the man are 6-13 ng/ml. Prolactin affects many organs, f.e. kidney, mamma, ovary, testis, hepar and skin. For clinical tests the raise in the serum levels after TSH or chlorpromacin and the drop after application of 2-brom-alpha-ergocryptin is used. Increased serum levels are found in patients with prolactin-producing tumors. In the male this is followed by disturbances of the sexual potency. Relations between prolactin and male infertility of gynecomastia are not yet known."}
{"id": "PMID:11198", "title": "Rapid microspectrofluorometric studies in EL2 cells following intracellular accumulation of dibenzocarbazoles.", "content": "Microspectrofluorometric observations were carried out in EL2 ascites cancer cells and dibenzo(a,e)fluoranthene (diB(a,e)F)-grown EL2 cells, following treatment (5 min) with three dibenzocarbazoles (1,2,7,8; 1,2,5,6 and 3,4,5,6). After microinjection of glucose-6-P leading to reduction of NAD(P), a sequence of difference spectra (after substrate minus before) is recorded. In dibenzocarbazole-untreated cells, maximum (NAD(P) reduction (emission maximum at 465-475 nm) is attained within 5 s, followed by a gradual return to initial fluorescence within 20 to 200 s (faster in the diB(a,e)F-grown). In dibenzocarbazole-treated cells there is a rather regular increase in the intensity of the difference spectrum up to approximately 300-500 s. Initially the increase is more predominant in the region around 460-470 nm, but it gains later prominence in the shorter wavelength region (420-430 nm) characteristic of the hydrocarbon (higher and steadier increase in the 3,4,5,6, dibenzocarbazole-treated diB(a,e)F-grown). Subsequently there is a gradual decrease of fluorescence which may or may or not return to initial level. The observed increase spectra require evaluation in terms of possible components (e.g. a mixture of NAD(P)H and hydrocarbon, binding changes, succession of fluorescent metabolites).", "contents": "Rapid microspectrofluorometric studies in EL2 cells following intracellular accumulation of dibenzocarbazoles. Microspectrofluorometric observations were carried out in EL2 ascites cancer cells and dibenzo(a,e)fluoranthene (diB(a,e)F)-grown EL2 cells, following treatment (5 min) with three dibenzocarbazoles (1,2,7,8; 1,2,5,6 and 3,4,5,6). After microinjection of glucose-6-P leading to reduction of NAD(P), a sequence of difference spectra (after substrate minus before) is recorded. In dibenzocarbazole-untreated cells, maximum (NAD(P) reduction (emission maximum at 465-475 nm) is attained within 5 s, followed by a gradual return to initial fluorescence within 20 to 200 s (faster in the diB(a,e)F-grown). In dibenzocarbazole-treated cells there is a rather regular increase in the intensity of the difference spectrum up to approximately 300-500 s. Initially the increase is more predominant in the region around 460-470 nm, but it gains later prominence in the shorter wavelength region (420-430 nm) characteristic of the hydrocarbon (higher and steadier increase in the 3,4,5,6, dibenzocarbazole-treated diB(a,e)F-grown). Subsequently there is a gradual decrease of fluorescence which may or may or not return to initial level. The observed increase spectra require evaluation in terms of possible components (e.g. a mixture of NAD(P)H and hydrocarbon, binding changes, succession of fluorescent metabolites)."}
{"id": "PMID:11196", "title": "Full-time course studies of bovine liver glutamate dehydrogenase. Simulation of inhibition by pyridoxal-5'-phosphate.", "content": "Inhibition of bovine liver glutamate dehydrogenase by pyridoxal-5'-phosphate was studied by measuring the full time course of the oxidation of NADPH. Progress curves were determined before and after incubation of the enzyme with PLP in the presence of saturating concentrations of alpha-ketoglutarate and ammonium ion, at pH 7.4 and 25 degrees C. The data were fitted to the integrated Michaelis-Menten equation and an inhibition model derived. According to the model, PLP inhibits the enzyme non-competitively, by reversible formation of the complexes E--PLP and E--PLP--NADPH; the oxidation of NADPH is also inhibited by NADP+. After incubation with PLP, the dissociation constants of E--NADPH and E--NADP+ (Km and Kp) show a very definite decrease, while the maximum rate of oxidation (Vm) is increased. The inhibition constants for PLP were also computed.", "contents": "Full-time course studies of bovine liver glutamate dehydrogenase. Simulation of inhibition by pyridoxal-5'-phosphate. Inhibition of bovine liver glutamate dehydrogenase by pyridoxal-5'-phosphate was studied by measuring the full time course of the oxidation of NADPH. Progress curves were determined before and after incubation of the enzyme with PLP in the presence of saturating concentrations of alpha-ketoglutarate and ammonium ion, at pH 7.4 and 25 degrees C. The data were fitted to the integrated Michaelis-Menten equation and an inhibition model derived. According to the model, PLP inhibits the enzyme non-competitively, by reversible formation of the complexes E--PLP and E--PLP--NADPH; the oxidation of NADPH is also inhibited by NADP+. After incubation with PLP, the dissociation constants of E--NADPH and E--NADP+ (Km and Kp) show a very definite decrease, while the maximum rate of oxidation (Vm) is increased. The inhibition constants for PLP were also computed."}
{"id": "PMID:11199", "title": "Adenosine triphosphate hydrolysis in rat dental tissues. A histochemical study of ion dependencies.", "content": "The effect of EDTA-decalcification, reactivating and activating procedures on the hydrolysis of ATP was studied histochemically in developing dental tissues in the rat. The incubation media contained lead citrate at alkaline pH and lead nitrate at neutral pH, and the results with ATP as substrate were compared with those obtained with beta-glycerophosphate. The ion dependency of ATP hydrolysis could only be ascertained in decalcified sections. As in earlier studies on the hydrolysis of beta-glycerophosphate in dental tissues, this hydrolysis could readily be reactivated through preincubation of the sections in a series of 0.1 M solutions of divalent cations; Zn2+ being the most efficient. This treatment was now found also to give rise to an ATP hydrolysis, which occurred without the need for activating ions in the incubation medium. This ATP hydrolysis should thus be described as nonspecific and, in terms of ion dependency, as due to a metalloenzyme, i.e. alkaline phosphatase. Activating ion dependent ATP hydrolysis in the dental tissues was found in the blood vessels and in the apical part of the secretory ameloblasts. The former was activated by Mg2+, Ca2+ and Mn2+, and the latter by Ca2+ and--almost specifically--by Sr2+. Preincubation with Zn2+ always inhibited the ion dependant ATP hydrolysis in the dental tissues.", "contents": "Adenosine triphosphate hydrolysis in rat dental tissues. A histochemical study of ion dependencies. The effect of EDTA-decalcification, reactivating and activating procedures on the hydrolysis of ATP was studied histochemically in developing dental tissues in the rat. The incubation media contained lead citrate at alkaline pH and lead nitrate at neutral pH, and the results with ATP as substrate were compared with those obtained with beta-glycerophosphate. The ion dependency of ATP hydrolysis could only be ascertained in decalcified sections. As in earlier studies on the hydrolysis of beta-glycerophosphate in dental tissues, this hydrolysis could readily be reactivated through preincubation of the sections in a series of 0.1 M solutions of divalent cations; Zn2+ being the most efficient. This treatment was now found also to give rise to an ATP hydrolysis, which occurred without the need for activating ions in the incubation medium. This ATP hydrolysis should thus be described as nonspecific and, in terms of ion dependency, as due to a metalloenzyme, i.e. alkaline phosphatase. Activating ion dependent ATP hydrolysis in the dental tissues was found in the blood vessels and in the apical part of the secretory ameloblasts. The former was activated by Mg2+, Ca2+ and Mn2+, and the latter by Ca2+ and--almost specifically--by Sr2+. Preincubation with Zn2+ always inhibited the ion dependant ATP hydrolysis in the dental tissues."}
{"id": "PMID:11200", "title": "[An improved histofluorescence procedure for freeze-dried paraffin-embedded tissue based on combined formaldehyde-glyoxylic acid perfusion with high magnesium content and acid pH].", "content": "A technique is described for highly sensitive and precise visualization of central catecholamine systems in paraffin sections of freeze-dried tissue. The procedure is based on perfusion of the animal with a solution containing formaldehyde and/or glyoxylic acid, in the presence of a very high magnesium content (40 g MgSO4/150 ml solution) and acid pH. The perfused tissue is rapidly frozen, freeze-dried, treated with formaldehyde vapours (at +80 degrees C for 1 h), embedded in parffin in vacuo, and finally sectioned. The present technique has a sensitivity for the dopamine- and noradrenaline-containing systems that is comparable with that of the glyoxylic acid-Vibratome technique, which utilizes fresh, glyoxylic acid-perfused tissue. Thus, the preterminal axon pathways become fluorescent throughout their full extent and the several new terminal systems, discovered with the glyoxylic acid-Vibratome method, are well demonstrable. The method is also highly useful for the study of the cell bodies and their dendritic processes. The catacholamine fibre systems are visualized without any signs of diffusion and with a richness in detail. In animals pretreated with L-tryptophan and MAO-inhibitor the technique is also useful for studies on central indolamine-containing systems.", "contents": "[An improved histofluorescence procedure for freeze-dried paraffin-embedded tissue based on combined formaldehyde-glyoxylic acid perfusion with high magnesium content and acid pH]. A technique is described for highly sensitive and precise visualization of central catecholamine systems in paraffin sections of freeze-dried tissue. The procedure is based on perfusion of the animal with a solution containing formaldehyde and/or glyoxylic acid, in the presence of a very high magnesium content (40 g MgSO4/150 ml solution) and acid pH. The perfused tissue is rapidly frozen, freeze-dried, treated with formaldehyde vapours (at +80 degrees C for 1 h), embedded in parffin in vacuo, and finally sectioned. The present technique has a sensitivity for the dopamine- and noradrenaline-containing systems that is comparable with that of the glyoxylic acid-Vibratome technique, which utilizes fresh, glyoxylic acid-perfused tissue. Thus, the preterminal axon pathways become fluorescent throughout their full extent and the several new terminal systems, discovered with the glyoxylic acid-Vibratome method, are well demonstrable. The method is also highly useful for the study of the cell bodies and their dendritic processes. The catacholamine fibre systems are visualized without any signs of diffusion and with a richness in detail. In animals pretreated with L-tryptophan and MAO-inhibitor the technique is also useful for studies on central indolamine-containing systems."}
{"id": "PMID:11201", "title": "[Pharmacologic aspects in the management of inner ear disease (author's transl)].", "content": "Our knowledge of the effects of drugs on the inner ear is extremely insufficient when compared to their effects on other organs. The role of drugs commonly recommended for therapy of inner ear disorders (such as, procaine, antihistaminics, diuretics, osmotics, corticoids and substances changing blood viscosity) has yet to be clarified since the clinical effects of these pharmaceuticals or vasoactive substances often cannot be confirmed by experimental study. Under present circumstances, the use of definitive therapy to prevent deafness has only limited application--as in thyroid hormone substitution to prevent deafness from cretinism.", "contents": "[Pharmacologic aspects in the management of inner ear disease (author's transl)]. Our knowledge of the effects of drugs on the inner ear is extremely insufficient when compared to their effects on other organs. The role of drugs commonly recommended for therapy of inner ear disorders (such as, procaine, antihistaminics, diuretics, osmotics, corticoids and substances changing blood viscosity) has yet to be clarified since the clinical effects of these pharmaceuticals or vasoactive substances often cannot be confirmed by experimental study. Under present circumstances, the use of definitive therapy to prevent deafness has only limited application--as in thyroid hormone substitution to prevent deafness from cretinism."}
{"id": "PMID:11205", "title": "Thin layer chromatographic identification of some sympathomimetic amines.", "content": "Thin layer chromatographic behavior of some sympathomimetic amines in the presence of acids in neutral and organic solvent systems is reported. The sympathomimetic amines were dissolved in 0.1N HCl or ethanol and treated with bromocresol green or p-nitrobenzoyl chloride reagents on fiber sheets or precoated glass plates. Two-, 3-, and 4-, component solvent systems were tested. Benzene-ethyl acetate gave 2 spots for each amine standard; the more polar spots were satisfactorily separated. Amines in pharmaccuticals were not separated by any solvent system tested.", "contents": "Thin layer chromatographic identification of some sympathomimetic amines. Thin layer chromatographic behavior of some sympathomimetic amines in the presence of acids in neutral and organic solvent systems is reported. The sympathomimetic amines were dissolved in 0.1N HCl or ethanol and treated with bromocresol green or p-nitrobenzoyl chloride reagents on fiber sheets or precoated glass plates. Two-, 3-, and 4-, component solvent systems were tested. Benzene-ethyl acetate gave 2 spots for each amine standard; the more polar spots were satisfactorily separated. Amines in pharmaccuticals were not separated by any solvent system tested."}
{"id": "PMID:11206", "title": "Evidence for a negative membrane potential and for movement of C1- against its electrochemical gradient in the ascomycete Neocosmospora vasinfecta.", "content": "The iodides of three lipid-soluble cations (dibenzyldimethylammonium; tribenzylmethylammonium, TBMA+; ethyldimethylbenzylammonium) were synthesized by the reaction of 14C-labeled methyl or 14C-labeled ethyl iodide with the appropriate secondary of tertiary amine and used in an attempt to measure the transmembrane electrical potential difference in Neocosmospora. Only mycelium containing high levels of Na+ accumulated measureable amounts of these cations and only above pH 6. Uptake was reduced in the presence of exogenous K+, Na+, Mg2+, or tris(hydroxymethyl)aminomethane. The velocity of TBMA+ uptake was proportional to its concentration between 46 and 427 muM. Neither the rate nor the extent of TBMB+ uptake was greatly affected by the presence of a fivefold excess of either dibenzyldimethylammonium or ethyldimethylbenzylammonium, even though these cations were themselves accumulated. The uncoupler m-chlorophenylhydrazone induced loss of previously accumulated TBMA+ from the mycelium. Anaerobiosis and cold (5 degrees C) temperature both inhibited TBMA+ uptake but did not induce the loss of previously accumulated TBMA+. The uptake of lipophilic cations by Na+-rich mycelium indicated a minimum transmembrane electrical potential of -60 to -70 mV (inside negative). Net uptake of these cations appeared to be strongly influenced by the availability of endogenous exchangeable cations and by the presence of other exogenous cations, as well as by the membrane potential. Despite these limitations, transport of C1- by Na+-rich mycelium appeared to take place against the electrochemical gradient for C1-.", "contents": "Evidence for a negative membrane potential and for movement of C1- against its electrochemical gradient in the ascomycete Neocosmospora vasinfecta. The iodides of three lipid-soluble cations (dibenzyldimethylammonium; tribenzylmethylammonium, TBMA+; ethyldimethylbenzylammonium) were synthesized by the reaction of 14C-labeled methyl or 14C-labeled ethyl iodide with the appropriate secondary of tertiary amine and used in an attempt to measure the transmembrane electrical potential difference in Neocosmospora. Only mycelium containing high levels of Na+ accumulated measureable amounts of these cations and only above pH 6. Uptake was reduced in the presence of exogenous K+, Na+, Mg2+, or tris(hydroxymethyl)aminomethane. The velocity of TBMA+ uptake was proportional to its concentration between 46 and 427 muM. Neither the rate nor the extent of TBMB+ uptake was greatly affected by the presence of a fivefold excess of either dibenzyldimethylammonium or ethyldimethylbenzylammonium, even though these cations were themselves accumulated. The uncoupler m-chlorophenylhydrazone induced loss of previously accumulated TBMA+ from the mycelium. Anaerobiosis and cold (5 degrees C) temperature both inhibited TBMA+ uptake but did not induce the loss of previously accumulated TBMA+. The uptake of lipophilic cations by Na+-rich mycelium indicated a minimum transmembrane electrical potential of -60 to -70 mV (inside negative). Net uptake of these cations appeared to be strongly influenced by the availability of endogenous exchangeable cations and by the presence of other exogenous cations, as well as by the membrane potential. Despite these limitations, transport of C1- by Na+-rich mycelium appeared to take place against the electrochemical gradient for C1-."}
{"id": "PMID:11207", "title": "Unique aspects of the regulation of the aspartate transcarbamylase of Serratia marcescens.", "content": "Aspartate trancarbamylase (ATC ase; EC 2.1.3.2) from Serratia marcescens HY has been purified 134-fold. Its properties are unique. Unlike the ATCase from Escherichia coli and Salmonella typhimurium, the S. marcescens HY enzyme activity is not feedback inhibited by any purine or pyrimidine nucleotide effectors; instead, the enzyme is activated by both cytidine 5'-triphosphate and adenosine 5'-triphosphate. Like the ATCase from E. coli and S. typhimurium, adenosine 5'-triphosphate alters the [S]0.5 of the enzyme and, in contrast, cytidine 5'-triphosphate does not alter the [S]0.5 but, instead, alters the Vmax. As has been shown for both E. coli and S . typhimurium, effector sensitivity may be selectively dissociated form catalytic activity by treatment with heat, parachloromercuribenzoate, or neohydrin. This dissociated enzyme possesses threefold higher specific activity than the native enzyme. The sedimentation coefficient of the native enzyme is approximately 11.4S, whereas the dissociated enzyme has a value of 6.0S. Whereas it has been possible to reconstitute the E. coli and the S. marcescens ATCase enzymes from their own homologous subunits, it has not been possible to make hybrid enzymes of catalytic and regulatory heterologous subunits from each other. It was not possible to detect repression of ATCase formation after growth of prototrophic strains of S. marcescens HY supplemented with 200 mug of uracil per ml, but eightfold derepression was observed after uracil withdrawal in pyrimidine auxotrophs.", "contents": "Unique aspects of the regulation of the aspartate transcarbamylase of Serratia marcescens. Aspartate trancarbamylase (ATC ase; EC 2.1.3.2) from Serratia marcescens HY has been purified 134-fold. Its properties are unique. Unlike the ATCase from Escherichia coli and Salmonella typhimurium, the S. marcescens HY enzyme activity is not feedback inhibited by any purine or pyrimidine nucleotide effectors; instead, the enzyme is activated by both cytidine 5'-triphosphate and adenosine 5'-triphosphate. Like the ATCase from E. coli and S. typhimurium, adenosine 5'-triphosphate alters the [S]0.5 of the enzyme and, in contrast, cytidine 5'-triphosphate does not alter the [S]0.5 but, instead, alters the Vmax. As has been shown for both E. coli and S . typhimurium, effector sensitivity may be selectively dissociated form catalytic activity by treatment with heat, parachloromercuribenzoate, or neohydrin. This dissociated enzyme possesses threefold higher specific activity than the native enzyme. The sedimentation coefficient of the native enzyme is approximately 11.4S, whereas the dissociated enzyme has a value of 6.0S. Whereas it has been possible to reconstitute the E. coli and the S. marcescens ATCase enzymes from their own homologous subunits, it has not been possible to make hybrid enzymes of catalytic and regulatory heterologous subunits from each other. It was not possible to detect repression of ATCase formation after growth of prototrophic strains of S. marcescens HY supplemented with 200 mug of uracil per ml, but eightfold derepression was observed after uracil withdrawal in pyrimidine auxotrophs."}
{"id": "PMID:11208", "title": "Reduced nicotinamide adenine dinucleotide oxidase activity in membranes and cytoplasm of Acholeplasma laidlawii and Mycoplasma mycoides subsp. capri.", "content": "The properties of the membrane-bound reduced nicotinamide adenine dinucleotide (NADH) oxidase of Acholeplasma laidlawii were compared with those of the corresponding cytoplasmic activity of Mycoplasma mycoides subsp. capri. The striking differences in pH optima, susceptibility to inhibitors and detergents, and heat inactivation between the NADH oxidase activity, with oxygen as an electron acceptor, and the NADH oxidoreductase activity, with dichlorophenol indophenol (DCPIP) as an alternate electron acceptor, support the presence of more than one catalytic protein in both the membrane-bound and soluble enzyme systems. The detection of more than one band positive for the NADH-nitroblue tetrazolium oxidoreductase reaction on electrophoresis of either the membranes of A. laidlawii or the cytoplasm of M mycoides subsp. capri also points in the same direction. The membrane-bound enzyme system differed, however, form the soluble one because it had a lower ratio of oxidase activity to oxidoreductase activity, and because it was less susceptible to heat inactivation and more readily incorporated incorporated into reaggregated membranes. In addition, the specific activity of the membrane-bound enzyme system increased as the culture aged, whereas that of the soluble system decreased as the culture aged. It is suggested that the different location in the cell could be responsible for some of the differences between the membrane-bound NADH oxidase activity of A. laidlawii and that found in the cytoplasm of M. mycoides subsp. capri.", "contents": "Reduced nicotinamide adenine dinucleotide oxidase activity in membranes and cytoplasm of Acholeplasma laidlawii and Mycoplasma mycoides subsp. capri. The properties of the membrane-bound reduced nicotinamide adenine dinucleotide (NADH) oxidase of Acholeplasma laidlawii were compared with those of the corresponding cytoplasmic activity of Mycoplasma mycoides subsp. capri. The striking differences in pH optima, susceptibility to inhibitors and detergents, and heat inactivation between the NADH oxidase activity, with oxygen as an electron acceptor, and the NADH oxidoreductase activity, with dichlorophenol indophenol (DCPIP) as an alternate electron acceptor, support the presence of more than one catalytic protein in both the membrane-bound and soluble enzyme systems. The detection of more than one band positive for the NADH-nitroblue tetrazolium oxidoreductase reaction on electrophoresis of either the membranes of A. laidlawii or the cytoplasm of M mycoides subsp. capri also points in the same direction. The membrane-bound enzyme system differed, however, form the soluble one because it had a lower ratio of oxidase activity to oxidoreductase activity, and because it was less susceptible to heat inactivation and more readily incorporated incorporated into reaggregated membranes. In addition, the specific activity of the membrane-bound enzyme system increased as the culture aged, whereas that of the soluble system decreased as the culture aged. It is suggested that the different location in the cell could be responsible for some of the differences between the membrane-bound NADH oxidase activity of A. laidlawii and that found in the cytoplasm of M. mycoides subsp. capri."}
{"id": "PMID:11210", "title": "Calcium transport ATPase of canine cardiac sarcoplasmic reticulum. A comparison with that of rabbit fast skeletal muscle sarcoplasmic reticulum.", "content": "To define the mechanism responsible for the slow rate of calcium transport by cardiac sarcoplasmic reticulum, the kinetic properties of the Ca2+-dependent ATPase of canine cardiac microsomes were characterized and compared with those of a comparable preparation from rabbit fast skeletal muscle. A phosphoprotein intermediate (E approximately P), which has the stability characteristics of an acyl phosphate, is formed during ATP hydrolysis by cardiac microsomes. Ca2+ is required for the E approximately P formation, and Mg2+ accelerates its decomposition. The Ca2+ concentration required for half-maximal activation of the ATPase is 4.7 +/- 0.2 muM for cardiac microsomes and 1.3 +/- 0.1 muM for skeletal microsomes at pH 6.8 and 0 degrees. The ATPase activities at saturating concentrations of ionized Ca2+ and pH 6.8, expressed as ATP hydrolysis per mg of protein, are 3 to 6 times lower for cardiac microsomes than for skeletal microsomes under a variety of conditions tested. The apparent Km value for MgATP at high concentrations in the presence of saturating concentrations of ionized Ca2+ is 0.18 +/- 0.03 ms at pH 6.8 and 25 degrees. The maximum velocity of ATPase activity under these conditions is 0.45 +/- 0.05 mumol per mg per min for cardiac microsomes and 1.60 +/- 0.05 mumol per mg per min for skeletal microsomes. The maximum steady state level of E approximately P for cardiac microsomes, 1.3 +/- 0.1 nmol per mg, is significantly less than the value of 4.9 +/- 0.2 nmol per mg for skeletal microsomes, so that the turnover number of the Ca2+-dependent ATPase of cardiac microsomes, calculated as the ratio of ATPase activity to the E approximately P level is similar to that of the skeletal ATPase. These findings indicate that the relatively slow rate of calcium transport by cardiac microsomes, whem compared to that of skeletal microsomes, reflects a lower density of calcium pumping sites and lower Ca2+ affinity for these sites, rather than a lower turnover rate.", "contents": "Calcium transport ATPase of canine cardiac sarcoplasmic reticulum. A comparison with that of rabbit fast skeletal muscle sarcoplasmic reticulum. To define the mechanism responsible for the slow rate of calcium transport by cardiac sarcoplasmic reticulum, the kinetic properties of the Ca2+-dependent ATPase of canine cardiac microsomes were characterized and compared with those of a comparable preparation from rabbit fast skeletal muscle. A phosphoprotein intermediate (E approximately P), which has the stability characteristics of an acyl phosphate, is formed during ATP hydrolysis by cardiac microsomes. Ca2+ is required for the E approximately P formation, and Mg2+ accelerates its decomposition. The Ca2+ concentration required for half-maximal activation of the ATPase is 4.7 +/- 0.2 muM for cardiac microsomes and 1.3 +/- 0.1 muM for skeletal microsomes at pH 6.8 and 0 degrees. The ATPase activities at saturating concentrations of ionized Ca2+ and pH 6.8, expressed as ATP hydrolysis per mg of protein, are 3 to 6 times lower for cardiac microsomes than for skeletal microsomes under a variety of conditions tested. The apparent Km value for MgATP at high concentrations in the presence of saturating concentrations of ionized Ca2+ is 0.18 +/- 0.03 ms at pH 6.8 and 25 degrees. The maximum velocity of ATPase activity under these conditions is 0.45 +/- 0.05 mumol per mg per min for cardiac microsomes and 1.60 +/- 0.05 mumol per mg per min for skeletal microsomes. The maximum steady state level of E approximately P for cardiac microsomes, 1.3 +/- 0.1 nmol per mg, is significantly less than the value of 4.9 +/- 0.2 nmol per mg for skeletal microsomes, so that the turnover number of the Ca2+-dependent ATPase of cardiac microsomes, calculated as the ratio of ATPase activity to the E approximately P level is similar to that of the skeletal ATPase. These findings indicate that the relatively slow rate of calcium transport by cardiac microsomes, whem compared to that of skeletal microsomes, reflects a lower density of calcium pumping sites and lower Ca2+ affinity for these sites, rather than a lower turnover rate."}
{"id": "PMID:11211", "title": "Purification and characterization of L-asparaginase with anti-lymphoma activity from Vibrio succinogenes.", "content": "Homogeneols L-asparaginase with anti-lymphoma activity was prepared from Vibrio succinogenes, an anaerobic bacterium from the bovine rumen. An overall yield of pure L-asparaginase of 40 to 45% and a specific activity of 200 +/- 2 IU per mg of protein was obtained. The pure enzyme can be stored at -20 degrees for at least 3 months with no loss of activity. The isoelectric point of the L-asparaginase is 8.74. No carbohydrate, phosphorus, tryptophan, disulfide, or sulfhydryl groups were detected. The enzyme has a molecular weight of 146,000 and a subunit weight of approximately 37,000. The Km of the enzyme for L-asparagine is 4.78 X 10(-5) M and the pH optimum of the L-asparaginase reaction is 7.3. D-Asparagine was hydrolyzed at 6.5% of the rate found with the L isomer. L-Glutamine and a variety of other amides were not hydrolyzed at significant rates; the activity of the enzyme for L-glutamine was 130- to 600-fold less than that of other therapeutically effective L-asparaginases of bacterial origin. The L-asparaginase from V. succinogenes is immunologically distinct from the L-asparaginase (EC-2) of Escherichia coli.", "contents": "Purification and characterization of L-asparaginase with anti-lymphoma activity from Vibrio succinogenes. Homogeneols L-asparaginase with anti-lymphoma activity was prepared from Vibrio succinogenes, an anaerobic bacterium from the bovine rumen. An overall yield of pure L-asparaginase of 40 to 45% and a specific activity of 200 +/- 2 IU per mg of protein was obtained. The pure enzyme can be stored at -20 degrees for at least 3 months with no loss of activity. The isoelectric point of the L-asparaginase is 8.74. No carbohydrate, phosphorus, tryptophan, disulfide, or sulfhydryl groups were detected. The enzyme has a molecular weight of 146,000 and a subunit weight of approximately 37,000. The Km of the enzyme for L-asparagine is 4.78 X 10(-5) M and the pH optimum of the L-asparaginase reaction is 7.3. D-Asparagine was hydrolyzed at 6.5% of the rate found with the L isomer. L-Glutamine and a variety of other amides were not hydrolyzed at significant rates; the activity of the enzyme for L-glutamine was 130- to 600-fold less than that of other therapeutically effective L-asparaginases of bacterial origin. The L-asparaginase from V. succinogenes is immunologically distinct from the L-asparaginase (EC-2) of Escherichia coli."}
{"id": "PMID:11212", "title": "Hydrogen ion interactions of horse spleen ferritin and apoferritin.", "content": "The interactions of horse spleen ferritin and its derivative apoferritin with H+ ions were studied by potentiometric and spectrophotometric titration; to aid in data analysis, heats of ionization over a limited pH range and amide content were also determined. Per apoferritin subunit, all tyrosine and cysteine side chains, two of the nine lysine side chains and at least three of the six histidine side chains were found not to titrate; a preliminary but self-consistent analysis of the titration data is proposed. The titration curve of ferritin was identical with that of apoferritin in the pH range 5.5 to 3. In addition, under the conditions used, the reactivities of ferritin histidines to bromoacetate and of ferritin lysines to formaldehyde were identical with those in apoferritin. Above pH 8, a time-dependent titration of the ferritin core occurs which prevents comparison of the titration curves of the two proteins in this region. However, in the pH regions 5.5 to 7.5, two extra groups per subunit titrate reversibly in ferritin relative to apoferritin. Moreover, although the isoionic points of ferritin and apoferritin are identical in water, the isoionic point of ferritin is 0.5 pH unit lower than that of apoferritin in 0.16 to 1 M KCl. The different effects of KCl and NaCl on the two proteins indicate the presence of cation binding sites in ferritin that are absent in apoferritin and possibly also the presence of anion binding sites in apoferritin that are occupied in ferritin by anions of the core. The difference between the isoionic points of the two proteins in KCl has been interpreted to indicate the presence of approximately 2 phosphate residues per ferritin subunit which serve as cation binding sites and which are negatively charged at the isoionic point in KCl. These phosphates may also represent the additional residues that titrate in ferritin between pH 5.5 and 7.5, or may interact with positively charged residues on the inner surface of the ferritin shell, or both.", "contents": "Hydrogen ion interactions of horse spleen ferritin and apoferritin. The interactions of horse spleen ferritin and its derivative apoferritin with H+ ions were studied by potentiometric and spectrophotometric titration; to aid in data analysis, heats of ionization over a limited pH range and amide content were also determined. Per apoferritin subunit, all tyrosine and cysteine side chains, two of the nine lysine side chains and at least three of the six histidine side chains were found not to titrate; a preliminary but self-consistent analysis of the titration data is proposed. The titration curve of ferritin was identical with that of apoferritin in the pH range 5.5 to 3. In addition, under the conditions used, the reactivities of ferritin histidines to bromoacetate and of ferritin lysines to formaldehyde were identical with those in apoferritin. Above pH 8, a time-dependent titration of the ferritin core occurs which prevents comparison of the titration curves of the two proteins in this region. However, in the pH regions 5.5 to 7.5, two extra groups per subunit titrate reversibly in ferritin relative to apoferritin. Moreover, although the isoionic points of ferritin and apoferritin are identical in water, the isoionic point of ferritin is 0.5 pH unit lower than that of apoferritin in 0.16 to 1 M KCl. The different effects of KCl and NaCl on the two proteins indicate the presence of cation binding sites in ferritin that are absent in apoferritin and possibly also the presence of anion binding sites in apoferritin that are occupied in ferritin by anions of the core. The difference between the isoionic points of the two proteins in KCl has been interpreted to indicate the presence of approximately 2 phosphate residues per ferritin subunit which serve as cation binding sites and which are negatively charged at the isoionic point in KCl. These phosphates may also represent the additional residues that titrate in ferritin between pH 5.5 and 7.5, or may interact with positively charged residues on the inner surface of the ferritin shell, or both."}
{"id": "PMID:11213", "title": "Purification and properties of two aromatic aminotransferases in Bacillus subtilis.", "content": "Two enzymes which transaminate tyrosine and phenylalanine in Bacillus subtilis were each purified over 200-fold and partially characterized. One of the enzymes, termed histidinol phosphate aminotransferase, is also active with imidazole acetyl phosphate as the amino group recipient. Previous studies have shown that mutants lacking this enzyme require histidine for growth. Mutants in the other enzyme termed aromatic aminotransferase are prototrophs. Neither enzyme is active on any other substrate involved in amino acid synthesis. The two enzymes can be distinguished by a number of criteria. Gel filtration analysis indicate the aromatic and histidinol phosphate aminotransferases have molecular weights of 63,500 and 33,000, respectively. Histidinol phosphate aminotransferase is heat-sensitive, whereas aromatic aminotransferase is relatively heat-stable, particularly in the presence of alpha-ketoglutarate. Both enzymes display typical Michaelis-Menten kinetics in their rates of reaction. The two enzymes have similar pH optima and employ a ping-pong mechanism of action. The Km values for various substrates suggest that histidinol phosphate aminotransferase is the predominant enzyme responsible for the transamaination reactions in the synthesis of tyrosine and phenylalanine. This enzyme has a 4-fold higher affinity for tyrosine and phenylalanine than does the aromatic aminotransferase. Competitive substrate inhibition was observed between tyrosine, phenylalanine, and histidinol phosphate for histidinol phosphate aminotransferase. The significance of the fact that an enzyme of histidine synthesis plays an important role in aromatic amino acid synthesis is discussed.", "contents": "Purification and properties of two aromatic aminotransferases in Bacillus subtilis. Two enzymes which transaminate tyrosine and phenylalanine in Bacillus subtilis were each purified over 200-fold and partially characterized. One of the enzymes, termed histidinol phosphate aminotransferase, is also active with imidazole acetyl phosphate as the amino group recipient. Previous studies have shown that mutants lacking this enzyme require histidine for growth. Mutants in the other enzyme termed aromatic aminotransferase are prototrophs. Neither enzyme is active on any other substrate involved in amino acid synthesis. The two enzymes can be distinguished by a number of criteria. Gel filtration analysis indicate the aromatic and histidinol phosphate aminotransferases have molecular weights of 63,500 and 33,000, respectively. Histidinol phosphate aminotransferase is heat-sensitive, whereas aromatic aminotransferase is relatively heat-stable, particularly in the presence of alpha-ketoglutarate. Both enzymes display typical Michaelis-Menten kinetics in their rates of reaction. The two enzymes have similar pH optima and employ a ping-pong mechanism of action. The Km values for various substrates suggest that histidinol phosphate aminotransferase is the predominant enzyme responsible for the transamaination reactions in the synthesis of tyrosine and phenylalanine. This enzyme has a 4-fold higher affinity for tyrosine and phenylalanine than does the aromatic aminotransferase. Competitive substrate inhibition was observed between tyrosine, phenylalanine, and histidinol phosphate for histidinol phosphate aminotransferase. The significance of the fact that an enzyme of histidine synthesis plays an important role in aromatic amino acid synthesis is discussed."}
{"id": "PMID:11214", "title": "A new oxygenase, 2-nitropropane dioxygenase of Hansenula mrakii. Enzymologic and spectrophotometric properties.", "content": "2-Nitropropane dioxygenase, purified to homogeneity from Hansenula mrakii (IFO 0895), has a molecular weight of approximately 62,000 and consists of two subunits nonidentical in molecular weight (39,000 and 25,000). Stoichiometrical studies and the results obtained with 18O2 showed that 2 atoms of molecular oxygen are incorporated into 2 molecules of acetone formed from 2-nitropropane. In addition to 2-nitropropane, nitroethane, 3-nitro-2-pentanol, and 1-nitropropane are oxidatively dentrified. The enzyme, which exhibits absorption maxima at 274, 370, 415, and 440 nm and a shoulder at 470 nm, contains 1 mol of FAD and 1 g atom of non-heme iron per mol of enzyme. The enzyme-bound FAD is reduced by 2-nitropropane under anaerogic conditions, but the enzyme-bound Fe3+ is not affected. The introduction of oxygen to the reduced form of enzyme causes reoxidation of the enzyme. The bound FAD and Fe3+ are reduced by the addition of nitromethane, which is not a substrate, under anaerobic conditions. The aerobic dialysis of the enzyme treated with nitromethane causes reoxidation of only the Fe2+. Sodium dithionite also reduces both the enzyme-bound FAD and Fe3+ under anaerobic conditions. When the enzyme is dialyzed against 10 mM potassium phosphate buffer (pH 7.0) immediately after reduction by dithionite, the absorption spectrum similar to that of the native enzyme appeared with concomitant restoration of approximately 80% of the activity. The enzyme activity is significantly inhibited by pyrocatechol-3,5-disulfonate disodium salt, 8-hydroxyquinoline, reducing agents such as 2-mercaptoethanol, and HgCl2. The Michaelis constants are as follows: 2-nitropropane (2.13 X 10(-2) M), nitroethane (2.43 X 10(-2) M), 3-nitro-2-pentanol (6.8 X 10(-3) M), 1-nitropropane (2.56 X 10(-2) M), and oxygen (3.03 X 10(-4) M, with 2-nitropropane).", "contents": "A new oxygenase, 2-nitropropane dioxygenase of Hansenula mrakii. Enzymologic and spectrophotometric properties. 2-Nitropropane dioxygenase, purified to homogeneity from Hansenula mrakii (IFO 0895), has a molecular weight of approximately 62,000 and consists of two subunits nonidentical in molecular weight (39,000 and 25,000). Stoichiometrical studies and the results obtained with 18O2 showed that 2 atoms of molecular oxygen are incorporated into 2 molecules of acetone formed from 2-nitropropane. In addition to 2-nitropropane, nitroethane, 3-nitro-2-pentanol, and 1-nitropropane are oxidatively dentrified. The enzyme, which exhibits absorption maxima at 274, 370, 415, and 440 nm and a shoulder at 470 nm, contains 1 mol of FAD and 1 g atom of non-heme iron per mol of enzyme. The enzyme-bound FAD is reduced by 2-nitropropane under anaerogic conditions, but the enzyme-bound Fe3+ is not affected. The introduction of oxygen to the reduced form of enzyme causes reoxidation of the enzyme. The bound FAD and Fe3+ are reduced by the addition of nitromethane, which is not a substrate, under anaerobic conditions. The aerobic dialysis of the enzyme treated with nitromethane causes reoxidation of only the Fe2+. Sodium dithionite also reduces both the enzyme-bound FAD and Fe3+ under anaerobic conditions. When the enzyme is dialyzed against 10 mM potassium phosphate buffer (pH 7.0) immediately after reduction by dithionite, the absorption spectrum similar to that of the native enzyme appeared with concomitant restoration of approximately 80% of the activity. The enzyme activity is significantly inhibited by pyrocatechol-3,5-disulfonate disodium salt, 8-hydroxyquinoline, reducing agents such as 2-mercaptoethanol, and HgCl2. The Michaelis constants are as follows: 2-nitropropane (2.13 X 10(-2) M), nitroethane (2.43 X 10(-2) M), 3-nitro-2-pentanol (6.8 X 10(-3) M), 1-nitropropane (2.56 X 10(-2) M), and oxygen (3.03 X 10(-4) M, with 2-nitropropane)."}
{"id": "PMID:11215", "title": "Reconstitution of biological molecular generators of electric current. H+-ATPase.", "content": "1. Generation of a transmembrane electric potential difference by oligomycin-sensitive ATPase complex, incorporated into spherical or planar phospholipid membrane, has been demonstrated. To this end, penetrating anion probe and direct voltmeter measurement of electric potential across phospholipid membrane were used. It was found that ATP-induced electric response is sensitive to oligomycin and protonophorous uncouplers. 2. The effect of variations in the phospholipid component of proteoliposomes on the electric generation was studied. It was revealed that the usage of mitochondrial phospholipids and phosphatidylethanolamine allows the highest values of membrane potential to be obtained in the case of ATPase proteoliposomes. In the case of cytochrome oxidase and bacteriorhodopsin proteoliposomes, phosphatidylserine was also shown to be quite suitable. Phosphatidylcholine was absolutely ineffective in all cases. 3. In proteoliposomes, containing both ATPase and bacteriorhodopsin, ATP and light induced generation of the electric field of the same direction. 4. In ATPase + cytochrome oxidase proteoliposomes, ATP hydrolysis and ascorbate oxidation was found to support electric generation of the same direction if cytochrome c was inside vesicles. Oxidation via external cytochrome c resulted in formation of electric field of the direction, opposite to that induced by ATP hydrolysis. 5. The data obtained in experiments with proteoliposomes of different types are discussed. The conclusion is made that conversion of energy of different resources into electric form is a common feature of membraneous energy transducers, which is in agreement with the Mitchellian principle of cellular energetics.", "contents": "Reconstitution of biological molecular generators of electric current. H+-ATPase. 1. Generation of a transmembrane electric potential difference by oligomycin-sensitive ATPase complex, incorporated into spherical or planar phospholipid membrane, has been demonstrated. To this end, penetrating anion probe and direct voltmeter measurement of electric potential across phospholipid membrane were used. It was found that ATP-induced electric response is sensitive to oligomycin and protonophorous uncouplers. 2. The effect of variations in the phospholipid component of proteoliposomes on the electric generation was studied. It was revealed that the usage of mitochondrial phospholipids and phosphatidylethanolamine allows the highest values of membrane potential to be obtained in the case of ATPase proteoliposomes. In the case of cytochrome oxidase and bacteriorhodopsin proteoliposomes, phosphatidylserine was also shown to be quite suitable. Phosphatidylcholine was absolutely ineffective in all cases. 3. In proteoliposomes, containing both ATPase and bacteriorhodopsin, ATP and light induced generation of the electric field of the same direction. 4. In ATPase + cytochrome oxidase proteoliposomes, ATP hydrolysis and ascorbate oxidation was found to support electric generation of the same direction if cytochrome c was inside vesicles. Oxidation via external cytochrome c resulted in formation of electric field of the direction, opposite to that induced by ATP hydrolysis. 5. The data obtained in experiments with proteoliposomes of different types are discussed. The conclusion is made that conversion of energy of different resources into electric form is a common feature of membraneous energy transducers, which is in agreement with the Mitchellian principle of cellular energetics."}
{"id": "PMID:11216", "title": "Mechanism of intramolecular activation of pepsinogen. Evidence for an intermediate delta and the involvement of the active site of pepsin in the intramolecular activation of pepsinogen.", "content": "Intramolecular pepsinogen activation is inhibited either by pepstatin, a potent pepsin inhibitor, or by purified globin from hemoglobin, a good pepsin substrate. Also, pepsinogen at pH 2 can be bound to a pepstatin-Sepharose column and recovered as native zymogen upon elution in pH 8 buffer. Kinetic studies of the globin inhibition of pepsinogen activation show that globin binds to a pepsinogen intermediate. This interaction gives rise to competitive inhibition of intramolecular pepsinogen activation. The evidence presented in this paper suggests that pepsinogen is converted rapidly upon acidification to the pepsinogen intermediate delta. In the absence of an inhibitor, the intermediate undergoes conformational change to bind the activation peptide portion of this same pepsinogen molecule in the active center to form an intramolecular enzyme-substrate complex (intermediate theta). This is followed by the intramolecular hydrolysis of the peptide bond between residues 44 and 45 of the pepsinogen molecule and the dissociation of the activation peptide from the pepsin. Intermediate delta apparently does not activate another pepsinogen molecule via an intermolecular process. Neither does intermediate delta hydrolyze globin substrate.", "contents": "Mechanism of intramolecular activation of pepsinogen. Evidence for an intermediate delta and the involvement of the active site of pepsin in the intramolecular activation of pepsinogen. Intramolecular pepsinogen activation is inhibited either by pepstatin, a potent pepsin inhibitor, or by purified globin from hemoglobin, a good pepsin substrate. Also, pepsinogen at pH 2 can be bound to a pepstatin-Sepharose column and recovered as native zymogen upon elution in pH 8 buffer. Kinetic studies of the globin inhibition of pepsinogen activation show that globin binds to a pepsinogen intermediate. This interaction gives rise to competitive inhibition of intramolecular pepsinogen activation. The evidence presented in this paper suggests that pepsinogen is converted rapidly upon acidification to the pepsinogen intermediate delta. In the absence of an inhibitor, the intermediate undergoes conformational change to bind the activation peptide portion of this same pepsinogen molecule in the active center to form an intramolecular enzyme-substrate complex (intermediate theta). This is followed by the intramolecular hydrolysis of the peptide bond between residues 44 and 45 of the pepsinogen molecule and the dissociation of the activation peptide from the pepsin. Intermediate delta apparently does not activate another pepsinogen molecule via an intermolecular process. Neither does intermediate delta hydrolyze globin substrate."}
{"id": "PMID:11217", "title": "Temperature dependence of cholesterol binding to cytochrome P-450scc of the rat adrenal. Effect of adrenocorticotropic hormone and cycloheximide.", "content": "A type I absorbance change is observed in suspensions of adrenal cortical mitochondria as the temperature is increased from 0-22 degrees. This \"heat-generated\" type I absorbance change is similar in magnitude to the pregnenolone-induced type II absorbance change of these mitochondria. Studies with inhibitors of cholesterol side chain cleavage indicate that the heat-generated type I absorbance change represents the specific interaction of cytochrome P-450scc with endogenous cholesterol in the mitochondria. This finding is confirmed by low temperature EPR spectroscopy on temperature-equilibrated, quick frozen adrenal mitochondrial samples. The EPR resonance at g = 8.2, which is that of the high spin cholesterol-bound cytochrome P-450scc, is absent in the samples incubated at 0 degrees and increases in magnitude with increasing temperature of incubation. Studies of the pH dependence of the heat-generated type I and pregnenolone-induced type II absorbance changes reveal that both are diminished by increasing pH over the range 6 to 8. Adrenocorticotropic hormone (ACTH) treatment of rats results in adrenal mitochondria which show a greatly increased heat-generated type I absorbance change. The latter correlates with an increased pregnenolone-induced type II absorbance change and increased EPR g = 8.2 signal. Prior treatment of animals with cycloheximide eliminated the ACTH-induced increase in the heat-generated type I absorbance change, the pregnenolone-induced type II absorbance change and the EPR g = 8.2 signal. We estimate that the hydrophobic bonding of cholesterol to cytochrome P-450scc occurs with a deltaH0' of approximately +15 kcal/mol and a deltaS0' of approximately +55 cal/mol deg. Our data support the concept of a labile protein which participates directly in this process.", "contents": "Temperature dependence of cholesterol binding to cytochrome P-450scc of the rat adrenal. Effect of adrenocorticotropic hormone and cycloheximide. A type I absorbance change is observed in suspensions of adrenal cortical mitochondria as the temperature is increased from 0-22 degrees. This \"heat-generated\" type I absorbance change is similar in magnitude to the pregnenolone-induced type II absorbance change of these mitochondria. Studies with inhibitors of cholesterol side chain cleavage indicate that the heat-generated type I absorbance change represents the specific interaction of cytochrome P-450scc with endogenous cholesterol in the mitochondria. This finding is confirmed by low temperature EPR spectroscopy on temperature-equilibrated, quick frozen adrenal mitochondrial samples. The EPR resonance at g = 8.2, which is that of the high spin cholesterol-bound cytochrome P-450scc, is absent in the samples incubated at 0 degrees and increases in magnitude with increasing temperature of incubation. Studies of the pH dependence of the heat-generated type I and pregnenolone-induced type II absorbance changes reveal that both are diminished by increasing pH over the range 6 to 8. Adrenocorticotropic hormone (ACTH) treatment of rats results in adrenal mitochondria which show a greatly increased heat-generated type I absorbance change. The latter correlates with an increased pregnenolone-induced type II absorbance change and increased EPR g = 8.2 signal. Prior treatment of animals with cycloheximide eliminated the ACTH-induced increase in the heat-generated type I absorbance change, the pregnenolone-induced type II absorbance change and the EPR g = 8.2 signal. We estimate that the hydrophobic bonding of cholesterol to cytochrome P-450scc occurs with a deltaH0' of approximately +15 kcal/mol and a deltaS0' of approximately +55 cal/mol deg. Our data support the concept of a labile protein which participates directly in this process."}
{"id": "PMID:11218", "title": "6-Phosphogluconate dehydrogenase. Purification and kinetics.", "content": "A method is described for the isolation and purification of 6-phosphogluconate dehydrogenase from pig liver. The molecular weight is estimated at 83,000 and that of the subunits is 42,000 as determined by gel electrophoresis. The pH maximum is 8.5 in 50 mM glycine/NaOH buffer and from 7.5 to 10 in 50 mM phosphate buffer at 30 degrees. Magnesium ion is not required for activity and acts as an inhibitor at concentrations above 20 mM. A cellular fractionation study indicates that this enzyme is located almost entirely within the soluble portion of the cytoplasm. Kinetic studies have been done in 50 mM glycine buffer, pH 8.5, at 30 degrees. The data are consistent with a sequential mechanism in which NADP+ is added first, followed by 6-phosphogluconate, and the products are released in the order, CO2, ribulose 5-phosphate, and NADPH. The Michaelis constant is 13.5 muM for 6-phosphogluconate. Dissociation constants are 4.8 muM for NADP+ and 5.1 muM for NADPH.", "contents": "6-Phosphogluconate dehydrogenase. Purification and kinetics. A method is described for the isolation and purification of 6-phosphogluconate dehydrogenase from pig liver. The molecular weight is estimated at 83,000 and that of the subunits is 42,000 as determined by gel electrophoresis. The pH maximum is 8.5 in 50 mM glycine/NaOH buffer and from 7.5 to 10 in 50 mM phosphate buffer at 30 degrees. Magnesium ion is not required for activity and acts as an inhibitor at concentrations above 20 mM. A cellular fractionation study indicates that this enzyme is located almost entirely within the soluble portion of the cytoplasm. Kinetic studies have been done in 50 mM glycine buffer, pH 8.5, at 30 degrees. The data are consistent with a sequential mechanism in which NADP+ is added first, followed by 6-phosphogluconate, and the products are released in the order, CO2, ribulose 5-phosphate, and NADPH. The Michaelis constant is 13.5 muM for 6-phosphogluconate. Dissociation constants are 4.8 muM for NADP+ and 5.1 muM for NADPH."}
{"id": "PMID:11219", "title": "Energy-dependent calcium transport in endoplasmic reticulum of adipocytes.", "content": "The endoplasmic reticulum from isolated rat adipocytes has the ability to actively accumulate calcium. The calcium uptake was characterized using the 20,000 X g supernatant (S1 fraction) of total cellular homogenate. Endoplasmic reticulum vesicles isolated from the S1 fraction as a 160,000 X g microsomal pellet prior to testing demonstrated little ability to accumulate calcium. The calcium uptake in the S1 fraction was localized to the endoplasmic reticulum vesicles by morphologic appearance, by the use of selective inhibitors of calcium uptake, and by high speed sedimentation of the accumulated calcium. The uptake was MgATP- and temperature-dependent and was sustained by the oxalate used as the intravesicular trapping agent. Uptake was linear with time for at least 30 min at all calcium concentrations tested (3 to 100 muM) and exhibited a pH optimum of approximately 7.0. The sulfhydryl inhibitor p-chloromercuribenzene sulfonate produced a dose-dependent inhibition of calcium uptake with total inhibition at 0.07 mumol/mg protein. Ruthenium red and sodium azide inhibited less than 5% of the uptake at concentrations (5 muM and 10 mM, respectively) which completely blocked calcium uptake by mitochondria isolated from the same cells. The Km for calcium uptake was 10 muM total calcium which corresponded to approximately 3.6 muM ionized calcium in the assay system. The maximum velocity of the uptake was 5.0 nmol (mg of microsomal protein)-1 (min)-1 at 24 degrees under the assay conditions used and exhibited a Q10 of 1.8. The uptake activity of the endoplasmic reticulum vesicles in the S1 fraction exhibited a marked time- and temperature-dependent lability which might account in part for the lack of uptake in the isolated microsomal fraction. This energy-dependent calcium uptake system would appear to be of physiologic importance to the regulation of intracellular calcium.", "contents": "Energy-dependent calcium transport in endoplasmic reticulum of adipocytes. The endoplasmic reticulum from isolated rat adipocytes has the ability to actively accumulate calcium. The calcium uptake was characterized using the 20,000 X g supernatant (S1 fraction) of total cellular homogenate. Endoplasmic reticulum vesicles isolated from the S1 fraction as a 160,000 X g microsomal pellet prior to testing demonstrated little ability to accumulate calcium. The calcium uptake in the S1 fraction was localized to the endoplasmic reticulum vesicles by morphologic appearance, by the use of selective inhibitors of calcium uptake, and by high speed sedimentation of the accumulated calcium. The uptake was MgATP- and temperature-dependent and was sustained by the oxalate used as the intravesicular trapping agent. Uptake was linear with time for at least 30 min at all calcium concentrations tested (3 to 100 muM) and exhibited a pH optimum of approximately 7.0. The sulfhydryl inhibitor p-chloromercuribenzene sulfonate produced a dose-dependent inhibition of calcium uptake with total inhibition at 0.07 mumol/mg protein. Ruthenium red and sodium azide inhibited less than 5% of the uptake at concentrations (5 muM and 10 mM, respectively) which completely blocked calcium uptake by mitochondria isolated from the same cells. The Km for calcium uptake was 10 muM total calcium which corresponded to approximately 3.6 muM ionized calcium in the assay system. The maximum velocity of the uptake was 5.0 nmol (mg of microsomal protein)-1 (min)-1 at 24 degrees under the assay conditions used and exhibited a Q10 of 1.8. The uptake activity of the endoplasmic reticulum vesicles in the S1 fraction exhibited a marked time- and temperature-dependent lability which might account in part for the lack of uptake in the isolated microsomal fraction. This energy-dependent calcium uptake system would appear to be of physiologic importance to the regulation of intracellular calcium."}
{"id": "PMID:11221", "title": "A quantitative description of the extension and retraction of surface protrusions in spreading 3T3 mouse fibroblasts.", "content": "We suggest a method of quantitating the motile actions of surface protrusions in spreading animal cells in culture. Its basis is the determination of the percentage of freshly plated cells which produce particle-free areas around them on a gold particle-coated glass cover slip within 50 min. Studying 3T3 cells with this assay, we found that the presence of Na+, K+, Cl-, and Mg++ or Ca++ in a neutral or slightly alkaline phosphate or bicarbonate buffered solution is sufficient to support the optimal particle removal by the cells for at least 50 min. Two metabolic inhibitors, 2,4-dinitrophenol and Na-azide, inhibit the particle removal. If D-glucose is added along with the inhibitors, particle removal can be restored, whereas the addition of three glucose analogues which are generally believed to be nonmetabolizable cannot restore the activity. Serum is not required for the mechanism(s) of the motile actions of surface protrusions in spreading 3T3 cells. However, it contains components which can neutralize the inhibitory actions of bovine serum albumin and several amino acids, particularly L-cystine or L-cystein and L-methionine. Furthermore, serum codetermines which of the major surface extension, filopodia, lamellipodia, or lobopodia, is predominantly active. We found three distinct classes of extracellular conditions under which the active surface projections are predominantly either lamellipodia, (sheetlike projections), lobopodia (blebs), or filopodia (microspikes). The quantitated dependencies on temperature, pH and the inhibition by cytochalasin B or the particle removal are very similar in all three cases. Preventing the cells from anchoring themselves for 15-20 min before plating in serum-free medium seems to stimulate particle removal threefold.", "contents": "A quantitative description of the extension and retraction of surface protrusions in spreading 3T3 mouse fibroblasts. We suggest a method of quantitating the motile actions of surface protrusions in spreading animal cells in culture. Its basis is the determination of the percentage of freshly plated cells which produce particle-free areas around them on a gold particle-coated glass cover slip within 50 min. Studying 3T3 cells with this assay, we found that the presence of Na+, K+, Cl-, and Mg++ or Ca++ in a neutral or slightly alkaline phosphate or bicarbonate buffered solution is sufficient to support the optimal particle removal by the cells for at least 50 min. Two metabolic inhibitors, 2,4-dinitrophenol and Na-azide, inhibit the particle removal. If D-glucose is added along with the inhibitors, particle removal can be restored, whereas the addition of three glucose analogues which are generally believed to be nonmetabolizable cannot restore the activity. Serum is not required for the mechanism(s) of the motile actions of surface protrusions in spreading 3T3 cells. However, it contains components which can neutralize the inhibitory actions of bovine serum albumin and several amino acids, particularly L-cystine or L-cystein and L-methionine. Furthermore, serum codetermines which of the major surface extension, filopodia, lamellipodia, or lobopodia, is predominantly active. We found three distinct classes of extracellular conditions under which the active surface projections are predominantly either lamellipodia, (sheetlike projections), lobopodia (blebs), or filopodia (microspikes). The quantitated dependencies on temperature, pH and the inhibition by cytochalasin B or the particle removal are very similar in all three cases. Preventing the cells from anchoring themselves for 15-20 min before plating in serum-free medium seems to stimulate particle removal threefold."}
{"id": "PMID:11220", "title": "Long-term results of mammary artery implants.", "content": "Eighty out of eighty-six patients (93%) with mammary artery implants were followed postoperatively for an average of three and a half years. The immediate mortality rate was 7% (6 cases), and the late mortality was 6% (5 cases). All had angina preoperatively. Twenty-four had a history of myocardial infarction and thirty-one were on limited physical activity, because of the pain. After surgery, thirty-three (45%) became asymptomatic. The angina improved significantly in thirty-five (47%) and remained unchanged in six (8%). Improvement in ventricular repolarization on ECG was observed in 69% of the patients. Postoperative cineangiography was performed in twenty-three patients; thirteen with single and ten with double implants. Out of the total of thirty-three implants, four (12%) were obstructed and twenty-seven patent (82%); twenty were in two cases of double implant, only one implant could be satisfactorily studied effectively functioning (61%). No obstructions were seen in the single implants. Non functioning implants were found in five (38%) of the thirteen single implants and in two of the twenty double ones (10%). The highest incidence of obstruction or non-functioning implants occurred in the group that did not show improvement (43%). This rate fell to 40% in the group that had some improvement and to 29% in those that were completely asymptomatic. Twelve of the eighteen patent mammary implants (67%) on the anterior wall of the left ventricle and eight of nine (89%) on the lateroinferior wall, established collateral circulation to the coronaries. Indication for surgery was considered satisfactory for nineteen out of the twenty-three patients and poor in four. There were two cases of obstruction of the implant (7%) in the group where surgery was correctly indicated and three of the twenty-three (11%) patent implants were non-functioning. Clinical improvement of the angina occurred in 84% in the first group and 50% in the other. In conclusion, this technique of indirect revascularization of the myocardium is valid for patients with severe diffuse lesions of the coronaries with a collateral network and preserved myocardial contractility.", "contents": "Long-term results of mammary artery implants. Eighty out of eighty-six patients (93%) with mammary artery implants were followed postoperatively for an average of three and a half years. The immediate mortality rate was 7% (6 cases), and the late mortality was 6% (5 cases). All had angina preoperatively. Twenty-four had a history of myocardial infarction and thirty-one were on limited physical activity, because of the pain. After surgery, thirty-three (45%) became asymptomatic. The angina improved significantly in thirty-five (47%) and remained unchanged in six (8%). Improvement in ventricular repolarization on ECG was observed in 69% of the patients. Postoperative cineangiography was performed in twenty-three patients; thirteen with single and ten with double implants. Out of the total of thirty-three implants, four (12%) were obstructed and twenty-seven patent (82%); twenty were in two cases of double implant, only one implant could be satisfactorily studied effectively functioning (61%). No obstructions were seen in the single implants. Non functioning implants were found in five (38%) of the thirteen single implants and in two of the twenty double ones (10%). The highest incidence of obstruction or non-functioning implants occurred in the group that did not show improvement (43%). This rate fell to 40% in the group that had some improvement and to 29% in those that were completely asymptomatic. Twelve of the eighteen patent mammary implants (67%) on the anterior wall of the left ventricle and eight of nine (89%) on the lateroinferior wall, established collateral circulation to the coronaries. Indication for surgery was considered satisfactory for nineteen out of the twenty-three patients and poor in four. There were two cases of obstruction of the implant (7%) in the group where surgery was correctly indicated and three of the twenty-three (11%) patent implants were non-functioning. Clinical improvement of the angina occurred in 84% in the first group and 50% in the other. In conclusion, this technique of indirect revascularization of the myocardium is valid for patients with severe diffuse lesions of the coronaries with a collateral network and preserved myocardial contractility."}
{"id": "PMID:11222", "title": "Brush border motility. Microvillar contraction in triton-treated brush borders isolated from intestinal epithelium.", "content": "The brush border of intestinal epithelial cells consists of an array of tightly packed microvilli. Within each microvillus is a bundle of 20-30 actin filaments. The basal ends of the filament bundles are embedded in and interconected by a filamentous meshwork, the terminal web, which lies directly beneath the microvilli. When calcium and ATP are added to isolated brush borders that have been treated with the detergent, Triton X-100, the microvillar filament bundles rapidly retract into and through the terminal web region. Biochemical studies of brush border contractile proteins suggest that the observed microvillar contraction is actomyosin mediated. We have shown previously that the major protein of the brush border's actin (Tilney, L. G., and M. S. Mooseker. 1971. Proc. Natl. Acad. Sci. U. S. A. 68:2611-2615). The brush border also contains a protein with the same molecular weight as the heavy chain subunit of myosin (200, 000 daltons). In addition, preparations of demembranated brush borders exhibit potassium-EDTA ATPase activity of 0.02 mumol phosphate/mg-min (22 degrees C); this assay is diagnostic for myosin-like ATPase isolated from vertebrate sources. Other proteins of the brush border include a 30,000 dalton protein with properties similar to those of tropomyosin, and a protein with the same molecular weight as the Z band protein, alpha-actinin (95,000 daltons). How these observations bear on the basis for microvillar movements in vivo is discussed within the framework of our recent model for the organization of actin and myosin in the brush border (Mooseker, M. S., and L. G. Tilney. 1975. J. Cell Biol. 67:725-743).", "contents": "Brush border motility. Microvillar contraction in triton-treated brush borders isolated from intestinal epithelium. The brush border of intestinal epithelial cells consists of an array of tightly packed microvilli. Within each microvillus is a bundle of 20-30 actin filaments. The basal ends of the filament bundles are embedded in and interconected by a filamentous meshwork, the terminal web, which lies directly beneath the microvilli. When calcium and ATP are added to isolated brush borders that have been treated with the detergent, Triton X-100, the microvillar filament bundles rapidly retract into and through the terminal web region. Biochemical studies of brush border contractile proteins suggest that the observed microvillar contraction is actomyosin mediated. We have shown previously that the major protein of the brush border's actin (Tilney, L. G., and M. S. Mooseker. 1971. Proc. Natl. Acad. Sci. U. S. A. 68:2611-2615). The brush border also contains a protein with the same molecular weight as the heavy chain subunit of myosin (200, 000 daltons). In addition, preparations of demembranated brush borders exhibit potassium-EDTA ATPase activity of 0.02 mumol phosphate/mg-min (22 degrees C); this assay is diagnostic for myosin-like ATPase isolated from vertebrate sources. Other proteins of the brush border include a 30,000 dalton protein with properties similar to those of tropomyosin, and a protein with the same molecular weight as the Z band protein, alpha-actinin (95,000 daltons). How these observations bear on the basis for microvillar movements in vivo is discussed within the framework of our recent model for the organization of actin and myosin in the brush border (Mooseker, M. S., and L. G. Tilney. 1975. J. Cell Biol. 67:725-743)."}
{"id": "PMID:11223", "title": "pH-dependent binding of immunoglobulins to intestinal cells of the neonatal rat.", "content": "Rat and rabbit IgG immunoglobulins conjugated to horseradiah peroxidase as a histochemical marker bind at 0 degrees C to the luminal surface of absorptive cells in isolated segments of jejunum from 10-12-day old rats. Binding is observed at pH 6.0, near the normal luminal pH of the duodenum and jejunum at this age, but not at pH 7.4. Furthermore, no binding occurs when cells are exposed at pH 6.0 to either free peroxidase or peroxidase conjugated to chicken or sheep IgG immunoglobulins or bovine serum albumin. The sensitivity of binding to pH suggests a means whereby immunoglobulins which are selectively absorbed by the cells can be released efficiently at the abluminal surface.", "contents": "pH-dependent binding of immunoglobulins to intestinal cells of the neonatal rat. Rat and rabbit IgG immunoglobulins conjugated to horseradiah peroxidase as a histochemical marker bind at 0 degrees C to the luminal surface of absorptive cells in isolated segments of jejunum from 10-12-day old rats. Binding is observed at pH 6.0, near the normal luminal pH of the duodenum and jejunum at this age, but not at pH 7.4. Furthermore, no binding occurs when cells are exposed at pH 6.0 to either free peroxidase or peroxidase conjugated to chicken or sheep IgG immunoglobulins or bovine serum albumin. The sensitivity of binding to pH suggests a means whereby immunoglobulins which are selectively absorbed by the cells can be released efficiently at the abluminal surface."}
{"id": "PMID:11224", "title": "Dietary phosphate deprivation in women and men: effects on mineral and acid balances, parathyroid hormone and the metabolism of 25-OH-vitamin D.", "content": "We evaluated the effects of dietary PO4 restriction on 25-OH-Vitamin D3 metabolism, serum iPTH levels, and mineral balances in healthy women and men. PO4 balances were progressively negative because of fecal losses without sex difference. Turnover of the plasma 25-OH-D pool was increased from 5.8 +/- 0.4 to 12 +/- 1.2 nmol/day; P less than 0.001, despite a fall in serum iPTH of -1.1 +/- 0.3 mulEq/ml; P less than 0.01. In both sexes, net intestinal calcium and magnesium absorption increased in proportion to a more rapid turnover of the plasma 25-OH-D pool, implying increased renal 1,25-(OH)2-D3 production. By contrast, there was a striking sex difference in the response of serum PO4 to dietary PO4 deprivation; the levels falling progressively in women, but remaining at control levels in men. Women demonstrated progressive hypercalciuria and negative Ca balances while in men the increments in intestinal Ca absorption were approximately matched by the increments in urinary Ca excretion so that Ca balances were not different from zero.", "contents": "Dietary phosphate deprivation in women and men: effects on mineral and acid balances, parathyroid hormone and the metabolism of 25-OH-vitamin D. We evaluated the effects of dietary PO4 restriction on 25-OH-Vitamin D3 metabolism, serum iPTH levels, and mineral balances in healthy women and men. PO4 balances were progressively negative because of fecal losses without sex difference. Turnover of the plasma 25-OH-D pool was increased from 5.8 +/- 0.4 to 12 +/- 1.2 nmol/day; P less than 0.001, despite a fall in serum iPTH of -1.1 +/- 0.3 mulEq/ml; P less than 0.01. In both sexes, net intestinal calcium and magnesium absorption increased in proportion to a more rapid turnover of the plasma 25-OH-D pool, implying increased renal 1,25-(OH)2-D3 production. By contrast, there was a striking sex difference in the response of serum PO4 to dietary PO4 deprivation; the levels falling progressively in women, but remaining at control levels in men. Women demonstrated progressive hypercalciuria and negative Ca balances while in men the increments in intestinal Ca absorption were approximately matched by the increments in urinary Ca excretion so that Ca balances were not different from zero."}
{"id": "PMID:11225", "title": "Size heterogeneity of human serum somatomedin.", "content": "Somatomedin (SM) in unextracted human serum was studied by Sephadex chromatography, starch gel electrophoresis, and in vitro SM bioassays. Repeated rechromatography of the various serum fractions revealed SM activity in a variety of indicated molecular size (IMS) areas; greater than 90,000, (very large); 90,000-20,000, (large); 20,000-9000, (intermediate); 9000-2000, (small); and less than 2000, (very small). Chromatography of unextracted serum, at pH 7.4, revealed 65% of SM as very large SM. Most of this very large SM remained stable at neutral pH; less than 25% appeared in smaller molecular sizes after acid eluent rechromatography. The latter significantly reassociated with other serum proteins in alkaline conditions. The large IMS SM was relatively stable on rehcromatography, whereas most of the intermediate IMS SM was converted to acidic small IMS SM proteins. The small IMS SM was stable, as a basic protein, after repeated acidic rechromatography. Most of the very small IMS SM occurred in a molecular size of less than 500. These results suggest the presence of multiple molecular size forms of SM in unextracted serum. Some of the larger SM represents an SM-serum protein aggregation. The acidic SM, with a molecular size near insulin, may be derived from a larger SM. The very small SM may be a nonpolypeptide substance(s).", "contents": "Size heterogeneity of human serum somatomedin. Somatomedin (SM) in unextracted human serum was studied by Sephadex chromatography, starch gel electrophoresis, and in vitro SM bioassays. Repeated rechromatography of the various serum fractions revealed SM activity in a variety of indicated molecular size (IMS) areas; greater than 90,000, (very large); 90,000-20,000, (large); 20,000-9000, (intermediate); 9000-2000, (small); and less than 2000, (very small). Chromatography of unextracted serum, at pH 7.4, revealed 65% of SM as very large SM. Most of this very large SM remained stable at neutral pH; less than 25% appeared in smaller molecular sizes after acid eluent rechromatography. The latter significantly reassociated with other serum proteins in alkaline conditions. The large IMS SM was relatively stable on rehcromatography, whereas most of the intermediate IMS SM was converted to acidic small IMS SM proteins. The small IMS SM was stable, as a basic protein, after repeated acidic rechromatography. Most of the very small IMS SM occurred in a molecular size of less than 500. These results suggest the presence of multiple molecular size forms of SM in unextracted serum. Some of the larger SM represents an SM-serum protein aggregation. The acidic SM, with a molecular size near insulin, may be derived from a larger SM. The very small SM may be a nonpolypeptide substance(s)."}
{"id": "PMID:11226", "title": "Evaluation of enrichment, storage, and age of blood agar medium in relation to its ability to support growth of anaerobic bacteria.", "content": "By measuring the colony size of a variety of anaerobic bacteria isolated from clinical specimens, an evaluation was made of the benefits derived from the addition of several enrichments to blood agar medium commonly used for the growth of anaerobes. Similar methods were used to study the effects of various storage conditions and age of the medium. The results were compared with those obtained on freshly prepared and enriched blood agar plates as well as commercially available blood agar plates. Freshly prepared and enriched blood agar was found to give substantially larger colonies than could be grown on commercially obtained blood agar plates when both were inoculated and incubated under identical conditions. Storage of plating media under CO2 for periods of up to 72 h had only a minor effect on the growth of the anaerobic bacteria studied, but longer periods of storage under CO2 resulted in a less efficient plating medium. Nonenriched brain heart infusion (BHI) was found to be a better basal medium than Trypticase soy agar (TSA) medium. Colony size on fully enriched BHI blood agar plates was greater than nonenriched BHI greater than nonenriched TSA greater than commercially prepared nonenriched TSA plates. The data suggest that freshness of the plates may be as important as using rich media.", "contents": "Evaluation of enrichment, storage, and age of blood agar medium in relation to its ability to support growth of anaerobic bacteria. By measuring the colony size of a variety of anaerobic bacteria isolated from clinical specimens, an evaluation was made of the benefits derived from the addition of several enrichments to blood agar medium commonly used for the growth of anaerobes. Similar methods were used to study the effects of various storage conditions and age of the medium. The results were compared with those obtained on freshly prepared and enriched blood agar plates as well as commercially available blood agar plates. Freshly prepared and enriched blood agar was found to give substantially larger colonies than could be grown on commercially obtained blood agar plates when both were inoculated and incubated under identical conditions. Storage of plating media under CO2 for periods of up to 72 h had only a minor effect on the growth of the anaerobic bacteria studied, but longer periods of storage under CO2 resulted in a less efficient plating medium. Nonenriched brain heart infusion (BHI) was found to be a better basal medium than Trypticase soy agar (TSA) medium. Colony size on fully enriched BHI blood agar plates was greater than nonenriched BHI greater than nonenriched TSA greater than commercially prepared nonenriched TSA plates. The data suggest that freshness of the plates may be as important as using rich media."}
{"id": "PMID:11227", "title": "Mycobactericidal activity of glutaraldehyde solutions.", "content": "Aqueous solutions of alkaline glutaraldehyde (buffered at pH 8.5) inactivated a standard suspension of Mycobacterium tuberculosis H37Rv faster than the corresponding acid (pH 3.7 preparation. Quantitative differences in the rate of inactivation of eight other species of Mycobacterium were determined using a 1% solution of alkaline glutaraldehyde and inactivation of residual glutaraldehyde with 1% sodium bisulfite solution. Variations in the rate of kill were observed between the various mycobacterial species tested, but such differences were probably not sufficiently large to be of practical importance. A 2% alkaline glutaraldehyde solution inactivated 10(5) viable M. tuberculosis cells present on the surface of porcelain penicylinders within 5 min at 18 degrees C. This rate of inactivation was faster than in the acidic solution.", "contents": "Mycobactericidal activity of glutaraldehyde solutions. Aqueous solutions of alkaline glutaraldehyde (buffered at pH 8.5) inactivated a standard suspension of Mycobacterium tuberculosis H37Rv faster than the corresponding acid (pH 3.7 preparation. Quantitative differences in the rate of inactivation of eight other species of Mycobacterium were determined using a 1% solution of alkaline glutaraldehyde and inactivation of residual glutaraldehyde with 1% sodium bisulfite solution. Variations in the rate of kill were observed between the various mycobacterial species tested, but such differences were probably not sufficiently large to be of practical importance. A 2% alkaline glutaraldehyde solution inactivated 10(5) viable M. tuberculosis cells present on the surface of porcelain penicylinders within 5 min at 18 degrees C. This rate of inactivation was faster than in the acidic solution."}
{"id": "PMID:11233", "title": "Coordination of classroom and clinical experience.", "content": "Clinical experience, providing opportunity to apply concepts and theories presented in the classroom, is essential in the education of a dietetic practitioner--whether it be as assistant, technician, or professional. Coordination of theory and practice is needed to permit students to acquire the knowledge, attitudes, and skills necessary for competent practice. Accountable program planners and instructors are responsible for presenting curricula designed to provide such coordinated classroom and clinical experiences in a relevant, holistic approach to the education of future dietetic practitioners.", "contents": "Coordination of classroom and clinical experience. Clinical experience, providing opportunity to apply concepts and theories presented in the classroom, is essential in the education of a dietetic practitioner--whether it be as assistant, technician, or professional. Coordination of theory and practice is needed to permit students to acquire the knowledge, attitudes, and skills necessary for competent practice. Accountable program planners and instructors are responsible for presenting curricula designed to provide such coordinated classroom and clinical experiences in a relevant, holistic approach to the education of future dietetic practitioners."}
{"id": "PMID:11260", "title": "Interaction of erythrocytes with human serum proteins. I. Analysis of the effect of pH and ionic strength of the medium.", "content": "The effect of ionic parameters of the medium (pH and ionic strength) on the processes of interaction of tannin-treated erythrocytes and the protein fractions of human serum (macroglobulins, microbulins and albumin) was studied in factorial experiments. Complex effect of these parametres on the processes under investigation and optimum conditions of erythrocyte sensitization were established. Subsequent fixation of antibodies by the erythrocyte diagnostic and their agglutinating activity are manifested in different mannera depending on the conditions of preceding sensitization. Important peculairities were discovered in the mechanism of interaction between the erythrocytes and various serum proteins. The obtained results should be taken into account in the production of erythrocyte antigen and antibody diagnosticums.", "contents": "Interaction of erythrocytes with human serum proteins. I. Analysis of the effect of pH and ionic strength of the medium. The effect of ionic parameters of the medium (pH and ionic strength) on the processes of interaction of tannin-treated erythrocytes and the protein fractions of human serum (macroglobulins, microbulins and albumin) was studied in factorial experiments. Complex effect of these parametres on the processes under investigation and optimum conditions of erythrocyte sensitization were established. Subsequent fixation of antibodies by the erythrocyte diagnostic and their agglutinating activity are manifested in different mannera depending on the conditions of preceding sensitization. Important peculairities were discovered in the mechanism of interaction between the erythrocytes and various serum proteins. The obtained results should be taken into account in the production of erythrocyte antigen and antibody diagnosticums."}
{"id": "PMID:11261", "title": "Tuberculin-sensitized lymphocytes detected by altered electrophorectic mobility distributions after incubation with the antigen PPD.", "content": "Lymphocytes from donors who had had tuberculosis (a disease known to provoke a cell-mediated immunity) were incubated with the tuberculin antigen, purified protein derivative (PPD), and their distribution of electrophoretic mobility was determined by laser Doppler spectroscopy. In 75% of the cases, the distribution showed a new, high mobility cell subpopulation that was not present before exposure to the PPD. Control lymphocytes from individuals with negative skin tests or no record of tuberculosis showed no mobility changes after incubation with PPD. These observations indicate that the new mobility subpopulation arose from a specific interaction between the antigen and sensitized cells of the donors.", "contents": "Tuberculin-sensitized lymphocytes detected by altered electrophorectic mobility distributions after incubation with the antigen PPD. Lymphocytes from donors who had had tuberculosis (a disease known to provoke a cell-mediated immunity) were incubated with the tuberculin antigen, purified protein derivative (PPD), and their distribution of electrophoretic mobility was determined by laser Doppler spectroscopy. In 75% of the cases, the distribution showed a new, high mobility cell subpopulation that was not present before exposure to the PPD. Control lymphocytes from individuals with negative skin tests or no record of tuberculosis showed no mobility changes after incubation with PPD. These observations indicate that the new mobility subpopulation arose from a specific interaction between the antigen and sensitized cells of the donors."}
{"id": "PMID:11264", "title": "Acyl specificity in triglyceride synthesis by lactating rat mammary gland.", "content": "We have studied the specificity of the acyl-CoA:diglyceride acyltransferase reaction in lactating rat mammary gland to provide a rational explanation at the enzyme level for the nonrandom distribution of fatty acids in milk fat triglycerides. Acyl-CoA:diglyceride acyltransferase activity was measured using various diglyceride and radioactive acyl-CoA substrates; products were identified as triglycerides by thin-layer and gas-liquid chromatography. Most of the enzymatic activity was located in the microsomal fraction and showed a broad specificity for the acyl donors tested C10, C12, C14, C16, C18, and C18:1 CoA esters). The acyltransferase activity was highly specific for sn-1,2-diglyceride enantiomers; rac-1,3- and sn-2,3-diglycerides were relatively inactive. The acyl-CoA specificity was not affected by the type of 1,2-diglyceride acceptor offered, although dilaurin was the best acceptor and sn-1,2-dilaurin greater than sn-1,2-dimyristin greater than sn-1,2-dipalmitin greater than sn-1,2-distearin. We have previously shown that in the microsomal fraction from lactating rat mammary gland, the acyltransferase activities concerned with the conversion of sn-glycero-3-phosphate to diacylglycerophosphate show a very marked specificity for long chain acyl-CoA's. Therefore, we conclude that the predominant localization of long chain fatty acids in the 1 and 2 positions, and of shorter chain fatty acids in the 3 position of the glycerol backbone, results at least in part from the specificities of the mammary gland acyltransferases.", "contents": "Acyl specificity in triglyceride synthesis by lactating rat mammary gland. We have studied the specificity of the acyl-CoA:diglyceride acyltransferase reaction in lactating rat mammary gland to provide a rational explanation at the enzyme level for the nonrandom distribution of fatty acids in milk fat triglycerides. Acyl-CoA:diglyceride acyltransferase activity was measured using various diglyceride and radioactive acyl-CoA substrates; products were identified as triglycerides by thin-layer and gas-liquid chromatography. Most of the enzymatic activity was located in the microsomal fraction and showed a broad specificity for the acyl donors tested C10, C12, C14, C16, C18, and C18:1 CoA esters). The acyltransferase activity was highly specific for sn-1,2-diglyceride enantiomers; rac-1,3- and sn-2,3-diglycerides were relatively inactive. The acyl-CoA specificity was not affected by the type of 1,2-diglyceride acceptor offered, although dilaurin was the best acceptor and sn-1,2-dilaurin greater than sn-1,2-dimyristin greater than sn-1,2-dipalmitin greater than sn-1,2-distearin. We have previously shown that in the microsomal fraction from lactating rat mammary gland, the acyltransferase activities concerned with the conversion of sn-glycero-3-phosphate to diacylglycerophosphate show a very marked specificity for long chain acyl-CoA's. Therefore, we conclude that the predominant localization of long chain fatty acids in the 1 and 2 positions, and of shorter chain fatty acids in the 3 position of the glycerol backbone, results at least in part from the specificities of the mammary gland acyltransferases."}
{"id": "PMID:11265", "title": "The coordinate roles of branchial nerve activity and potassium in the stimulation of ciliary activity in Mytilus edulis: observations with phenoxybenzamine, bromolysergic acid and fluorescence histochemistry.", "content": "Potassium concentrations in excess of 30 mM increase the rate of beating of lateral cilia on the gill of Mytilus edulis. Cilioexcitation produced by low frequency (5 beats/s) electrical stimulation was potentiated with potassium but blocked with bromolysergic acid (a serotonergic inhibitor). Cilioinhibition produced by high frequency (50 beats/s) stimulation was decreased with potassium and phenoxybenzamine (a dopaminergic inhibitor). Phenoxybenzamine enhanced the cilioexcitation produced by potassium. Potassium doses incapable of maintaining a basal rate of beating (less than 30 mM) could increase ciliary activity if phenoxybenzamine was also added. After transection of the branchial nerve, the yellow-fluorophore (serotonergic storage) and cilioexcitatory effect of potassium gradually decrease. This study shows that the potassium effect on ciliary activity (a) increase with low frequency nerve stimulation, presumably through the release of serotonin and (b) decreases with high frequency nerve stimulation, presumably through the release of dopamine.", "contents": "The coordinate roles of branchial nerve activity and potassium in the stimulation of ciliary activity in Mytilus edulis: observations with phenoxybenzamine, bromolysergic acid and fluorescence histochemistry. Potassium concentrations in excess of 30 mM increase the rate of beating of lateral cilia on the gill of Mytilus edulis. Cilioexcitation produced by low frequency (5 beats/s) electrical stimulation was potentiated with potassium but blocked with bromolysergic acid (a serotonergic inhibitor). Cilioinhibition produced by high frequency (50 beats/s) stimulation was decreased with potassium and phenoxybenzamine (a dopaminergic inhibitor). Phenoxybenzamine enhanced the cilioexcitation produced by potassium. Potassium doses incapable of maintaining a basal rate of beating (less than 30 mM) could increase ciliary activity if phenoxybenzamine was also added. After transection of the branchial nerve, the yellow-fluorophore (serotonergic storage) and cilioexcitatory effect of potassium gradually decrease. This study shows that the potassium effect on ciliary activity (a) increase with low frequency nerve stimulation, presumably through the release of serotonin and (b) decreases with high frequency nerve stimulation, presumably through the release of dopamine."}
{"id": "PMID:11266", "title": "Proline inhibition of a sea anemone alarm pheromone response.", "content": "1. L-proline, by itself or in animal tissue extracts, inhibits the response of the sea anemone Anthopleura elegantissima to the alarm phermone, anthopeurine. 2. The effect of proline is mediated by a receptor that is specific for the structure and configuration of the part of the L-proline molecule containing the carboxyl and imino groups. 3. Proline inhibition is competitive, in the sense that the effects of a given proline concentration can be overridden by an increase in anthopeurine concentration. 4. The magnitude of proline inhibition increases with proline concentration and decreases as the duration of exposure to proline increases. 5. Neither the final conducting system mediating the alarm response nor the responding muscles are inhbited by proline. Inhibition presumably occurs at or soon after the level of anthopleurine receptors. 6. Proline inhibition may resolve the potential conflict between Anthopleura's mutually exclusive feeding and alarm pheromone responses.", "contents": "Proline inhibition of a sea anemone alarm pheromone response. 1. L-proline, by itself or in animal tissue extracts, inhibits the response of the sea anemone Anthopleura elegantissima to the alarm phermone, anthopeurine. 2. The effect of proline is mediated by a receptor that is specific for the structure and configuration of the part of the L-proline molecule containing the carboxyl and imino groups. 3. Proline inhibition is competitive, in the sense that the effects of a given proline concentration can be overridden by an increase in anthopeurine concentration. 4. The magnitude of proline inhibition increases with proline concentration and decreases as the duration of exposure to proline increases. 5. Neither the final conducting system mediating the alarm response nor the responding muscles are inhbited by proline. Inhibition presumably occurs at or soon after the level of anthopleurine receptors. 6. Proline inhibition may resolve the potential conflict between Anthopleura's mutually exclusive feeding and alarm pheromone responses."}
{"id": "PMID:11267", "title": "An electrolytic method for determining oxygen dissociation curves using small blood samples: the effect of temperature on trout and human blood.", "content": "1. A detailed account is given of an electrolytic method for determining the oxygen dissociation curve of fish blood using a single sample of 50-100 mul for the whole curve. The accuracy and some of the problems arising from its uses are discussed. 2. Oxygen dissociation curves have been determined for trout blood and human blood at temperatures of 15 and 37 degrees C. The relationship between P50 and temperature is similar to that obtained using other methods. Absolute values of P50 are generally lower than those obtained by other methods, especially in the case of fish blood. 3. The effect of PCO2 and pH on the oxygen dissociation curve of trout blood is tested and it is shown that PCO2 has a more marked effect than pH when the other factor is maintained at a constant level. The Bohr factor (delta log P50/delta pH) appears to be approximately the same and independent of the PCO2. 4. The P50 of ray blood determined from fish during and after an operation showed an increased Bohr factor.", "contents": "An electrolytic method for determining oxygen dissociation curves using small blood samples: the effect of temperature on trout and human blood. 1. A detailed account is given of an electrolytic method for determining the oxygen dissociation curve of fish blood using a single sample of 50-100 mul for the whole curve. The accuracy and some of the problems arising from its uses are discussed. 2. Oxygen dissociation curves have been determined for trout blood and human blood at temperatures of 15 and 37 degrees C. The relationship between P50 and temperature is similar to that obtained using other methods. Absolute values of P50 are generally lower than those obtained by other methods, especially in the case of fish blood. 3. The effect of PCO2 and pH on the oxygen dissociation curve of trout blood is tested and it is shown that PCO2 has a more marked effect than pH when the other factor is maintained at a constant level. The Bohr factor (delta log P50/delta pH) appears to be approximately the same and independent of the PCO2. 4. The P50 of ray blood determined from fish during and after an operation showed an increased Bohr factor."}
{"id": "PMID:11268", "title": "Physiology of an ATP receptor in labellar sensilla of the tsetse fly Glossina morsitans morsitans Westw. (Diptera: Glossinidae).", "content": "Electrophysiological recordings have been made from cells in the eight large, labellar sensilla of g. morsitans. One of these cells in each sensillum was shown to respond to ATP over a concentration range of 10(-6)-10(-3) M. It was also sensitive to several other adenosine phophates, but much less sensitive to CTP, GTP and ITP. The activity of the receptor was depressed below pH 7, and sometimes considerably increased above pH 9. These aspects the receptor's physiology support the results of behavioural studies. It is concluded that the eight receptors mediate the flies' behavioural response to ATP.", "contents": "Physiology of an ATP receptor in labellar sensilla of the tsetse fly Glossina morsitans morsitans Westw. (Diptera: Glossinidae). Electrophysiological recordings have been made from cells in the eight large, labellar sensilla of g. morsitans. One of these cells in each sensillum was shown to respond to ATP over a concentration range of 10(-6)-10(-3) M. It was also sensitive to several other adenosine phophates, but much less sensitive to CTP, GTP and ITP. The activity of the receptor was depressed below pH 7, and sometimes considerably increased above pH 9. These aspects the receptor's physiology support the results of behavioural studies. It is concluded that the eight receptors mediate the flies' behavioural response to ATP."}
{"id": "PMID:11269", "title": "Nervous control of light responses in the sea anemone, Calamactis praelongus.", "content": "1. The burrowing sea anemone, Calamactis praelongus, responds to light with local, non-nervous contractions of the column. There are also more extensive responses of the column and retractor muscles co-ordinated by nerve net pulses (NNP's) under pacemaker control. 2. NNP's occur in at least two types of bursts and in sequences which sometimes indicate a rotating site of pulse initiation. 3. Light-evoked NNP sequences can be tape recorded and used later to drive a stimulator to reproduce the original sequences in the same or different anemones, evoking muscular responses which approximate the originals. This technique separates the pacemaker-directed component of the light response from the local effects of light stimulation. 4. Isolated circular and parietal muscles contract slowly when stimulated by light or excited indirectly by NNP's. Retractor muscles are insensitive to light but produce rapid contractions when excited by closely spaced light-evoked NNP's. 5. A model for light responses is proposed which incorporates the characteristics of isolated muscles  and intact anemones.", "contents": "Nervous control of light responses in the sea anemone, Calamactis praelongus. 1. The burrowing sea anemone, Calamactis praelongus, responds to light with local, non-nervous contractions of the column. There are also more extensive responses of the column and retractor muscles co-ordinated by nerve net pulses (NNP's) under pacemaker control. 2. NNP's occur in at least two types of bursts and in sequences which sometimes indicate a rotating site of pulse initiation. 3. Light-evoked NNP sequences can be tape recorded and used later to drive a stimulator to reproduce the original sequences in the same or different anemones, evoking muscular responses which approximate the originals. This technique separates the pacemaker-directed component of the light response from the local effects of light stimulation. 4. Isolated circular and parietal muscles contract slowly when stimulated by light or excited indirectly by NNP's. Retractor muscles are insensitive to light but produce rapid contractions when excited by closely spaced light-evoked NNP's. 5. A model for light responses is proposed which incorporates the characteristics of isolated muscles  and intact anemones."}
{"id": "PMID:11270", "title": "Active H+ transport in the turtle urinary bladder. Coupling of transport to glucose oxidation.", "content": "The turtle urinary bladder acidifies the contents of its lumen by actively transporting protons. H+ secretion by the isolated bladder was measured simultaneously with the rate of 14CO2 evolution from [14C]glucose. The application of an adverse pH gradient resulted in a decline in the rate of H+ secretion (JH) and in the rate of glucose oxidation (JCO2). The changes in JH and JCO2 were linear functions of the pH difference across the membrane. Hence, JH and JCO2 were linearly related to each other. The slope, deltaJH/deltaJCO2 was found to be similar in half-bladders from the same animal but was seen to vary widely in a population of turtles. To investigate the effect of pH gradients on deltaJH/deltaJCO2, two experiments were performed in each of 14 hemibladders. In one, JH and JCO2 were altered by changing the luminal pH. In the other, they were altered by changing the ambient pCO2 while the luminal pH was kept constant. The average slope, deltaJH/deltaJCO2, in the presence of pH gradients was 14.45 eq-mol-1. In the absence of gradients in the same hemibladders it was 14.72, delta = 0.27 +/- 1.46. The results show that H+ transport is organized in such a way that leaks to protons in parallel to the pump are negligible. Analysis of the transport system by use of the Essig-Caplan linear irreversible thermodynamic formalism shows that the system is tightly coupled. The degree of coupling, q, given by that analysis was measured and found to be at or very near the maximum theoretical value.", "contents": "Active H+ transport in the turtle urinary bladder. Coupling of transport to glucose oxidation. The turtle urinary bladder acidifies the contents of its lumen by actively transporting protons. H+ secretion by the isolated bladder was measured simultaneously with the rate of 14CO2 evolution from [14C]glucose. The application of an adverse pH gradient resulted in a decline in the rate of H+ secretion (JH) and in the rate of glucose oxidation (JCO2). The changes in JH and JCO2 were linear functions of the pH difference across the membrane. Hence, JH and JCO2 were linearly related to each other. The slope, deltaJH/deltaJCO2 was found to be similar in half-bladders from the same animal but was seen to vary widely in a population of turtles. To investigate the effect of pH gradients on deltaJH/deltaJCO2, two experiments were performed in each of 14 hemibladders. In one, JH and JCO2 were altered by changing the luminal pH. In the other, they were altered by changing the ambient pCO2 while the luminal pH was kept constant. The average slope, deltaJH/deltaJCO2, in the presence of pH gradients was 14.45 eq-mol-1. In the absence of gradients in the same hemibladders it was 14.72, delta = 0.27 +/- 1.46. The results show that H+ transport is organized in such a way that leaks to protons in parallel to the pump are negligible. Analysis of the transport system by use of the Essig-Caplan linear irreversible thermodynamic formalism shows that the system is tightly coupled. The degree of coupling, q, given by that analysis was measured and found to be at or very near the maximum theoretical value."}
{"id": "PMID:11271", "title": "Analysis of the rhodopsin cycle in limulus ventral photoreceptors using the early receptor potential.", "content": "The early receptor potential (ERP) was recorded intracellularly from Limulus ventral photoreceptors. The ERP in cells dissected under red light was altered by exhaustive illumination. No recovery to the original wafeform was observed, even after 1 h in the dark. The ERP waveform could be further altered by chromatic adaptation or by changes in pH. The results indicate that at pH 7.8 there are two interconvertible pigment states with only slightly different lambdamax, whereas at pH 9.6 there are two interconvertible states with very different lambdamax. Under all conditions studied the ERPs were almost identical with those previously obtained in squid retinas. This strongly suggests that light converts Limulus rhodopsin to a stable photoequilibrium mixture of rhodopsin to a stable photoequilibrium mixture of rhodopsin and metarhodopsin and that, as in squid, the lambdamax of metarhodopsin depends on pH. This conversion at pH 7.8 is associated with a small (0.7 log unit) decrease in the maximum sensitivity of the late receptor potential. Thus the component of adaptation linked to changes in rhodopsin concentration is unimportant in comparison to the \"neural\" component.", "contents": "Analysis of the rhodopsin cycle in limulus ventral photoreceptors using the early receptor potential. The early receptor potential (ERP) was recorded intracellularly from Limulus ventral photoreceptors. The ERP in cells dissected under red light was altered by exhaustive illumination. No recovery to the original wafeform was observed, even after 1 h in the dark. The ERP waveform could be further altered by chromatic adaptation or by changes in pH. The results indicate that at pH 7.8 there are two interconvertible pigment states with only slightly different lambdamax, whereas at pH 9.6 there are two interconvertible states with very different lambdamax. Under all conditions studied the ERPs were almost identical with those previously obtained in squid retinas. This strongly suggests that light converts Limulus rhodopsin to a stable photoequilibrium mixture of rhodopsin to a stable photoequilibrium mixture of rhodopsin and metarhodopsin and that, as in squid, the lambdamax of metarhodopsin depends on pH. This conversion at pH 7.8 is associated with a small (0.7 log unit) decrease in the maximum sensitivity of the late receptor potential. Thus the component of adaptation linked to changes in rhodopsin concentration is unimportant in comparison to the \"neural\" component."}
{"id": "PMID:11272", "title": "Ion permeability of isolated chromaffin granules.", "content": "The passive ion permeability, regulation of volume, and internal pH of isolated bovine chromaffin granules were studied by radiochemical, potentiometric, gravimetric, and spectrophotometric techniques. Chromaffin granules behave as perfect osmometers between 340 and 1,000 mosM in choline chloride, NaCl, and KCl as measured by changes in absorbance at 430 nm or from intragranular water measurements using 3H2O and [14C]polydextran. By suspending chromaffin granules in iso-osmotic media of various metal ions and selectively increasing the permeability to either the cation or the anion by intrinsically permeable ions or specific ionophores, it was possible to determine by turbidity and potentiometric measurements the permeability to the counterion. These measurements indicate that the chromaffin granule is impermeable to the cations tested (Na+, K+, and H+). Limited H+ permeability across the chromaffin granule membrane was also shown by means of the time course of pH re-equilibration after pulsed pH changes in the surrounding media. The measurement of [14C]methylamine distribution indicates that a significant deltapH exists across the membrane, inside acidic, which at an external value of 6.85 has a value of 1.16. The deltapH is relatively insensitive to changes in the composition of the external media and can be enhanced or collapsed by the addition of ionophores and uncouplers. Measurement at various values of external pH indicates an internal pH of 5.5. Use of the ionophore A23187 indicates that Ca++ and Mg++ can be accumulated against an apparent concentration gradient with calcium uptake exceeding 50 nmol/mg of protein at saturation. These measurements also show that Ca++ and Mg++ are impermeable. Measurement of catecholamine release under conditions where intravesicular calcium accumulation is maximal indicates that catecholamine release does not occur. The physiological significance of the high impermeability to ions and the existence of a large deltapH are discussed in terms of regulation of uptake, storage, and release of catecholamines in chromaffin granules.", "contents": "Ion permeability of isolated chromaffin granules. The passive ion permeability, regulation of volume, and internal pH of isolated bovine chromaffin granules were studied by radiochemical, potentiometric, gravimetric, and spectrophotometric techniques. Chromaffin granules behave as perfect osmometers between 340 and 1,000 mosM in choline chloride, NaCl, and KCl as measured by changes in absorbance at 430 nm or from intragranular water measurements using 3H2O and [14C]polydextran. By suspending chromaffin granules in iso-osmotic media of various metal ions and selectively increasing the permeability to either the cation or the anion by intrinsically permeable ions or specific ionophores, it was possible to determine by turbidity and potentiometric measurements the permeability to the counterion. These measurements indicate that the chromaffin granule is impermeable to the cations tested (Na+, K+, and H+). Limited H+ permeability across the chromaffin granule membrane was also shown by means of the time course of pH re-equilibration after pulsed pH changes in the surrounding media. The measurement of [14C]methylamine distribution indicates that a significant deltapH exists across the membrane, inside acidic, which at an external value of 6.85 has a value of 1.16. The deltapH is relatively insensitive to changes in the composition of the external media and can be enhanced or collapsed by the addition of ionophores and uncouplers. Measurement at various values of external pH indicates an internal pH of 5.5. Use of the ionophore A23187 indicates that Ca++ and Mg++ can be accumulated against an apparent concentration gradient with calcium uptake exceeding 50 nmol/mg of protein at saturation. These measurements also show that Ca++ and Mg++ are impermeable. Measurement of catecholamine release under conditions where intravesicular calcium accumulation is maximal indicates that catecholamine release does not occur. The physiological significance of the high impermeability to ions and the existence of a large deltapH are discussed in terms of regulation of uptake, storage, and release of catecholamines in chromaffin granules."}
{"id": "PMID:11273", "title": "Microcalorimetric detection of growth of Mycoplasmatales.", "content": "A static ampoule microcalorimeter was used to study the growth of mycoplasmas, acholeplasmas and ureaplasmas. Growth as indicated by thermograms was compared with the results of conventional methods, namely, terminal dilution counts, plate counts, turbidimetric measurements, glucose consumption and pH changes. Removal of oxygen had little effect on mycoplasma growth. The microcalorimetric method is potentially useful for identifying and enumerating the members of the Mycoplasmatales.", "contents": "Microcalorimetric detection of growth of Mycoplasmatales. A static ampoule microcalorimeter was used to study the growth of mycoplasmas, acholeplasmas and ureaplasmas. Growth as indicated by thermograms was compared with the results of conventional methods, namely, terminal dilution counts, plate counts, turbidimetric measurements, glucose consumption and pH changes. Removal of oxygen had little effect on mycoplasma growth. The microcalorimetric method is potentially useful for identifying and enumerating the members of the Mycoplasmatales."}
{"id": "PMID:11274", "title": "The effect of hydrogen peroxide on spores of Clostridium bifermentans.", "content": "The effect of hydrogen peroxide on the germination, colony formation and structure of spores of Clostridium bifermentans was examined. Treatment with 0.35 M-hydrogen peroxide increased the germination rate at 25 degrees C but increasing the temperature or concentration of hydrogen peroxide decreased both the germination rate and colony formation. The presence of Cu2+ increased the lethal effect of hydrogen peroxide on colony formation as much as 3000-fold. Pre-incubation of spores with Cu2+ before treatment with hydrogen peroxide produced a similar increase, but this could be eliminated by washing the spores with dilute spores--apparently from the coat--and treatment with dithiothreitol, which also removes spore-coat protein, increased the lethal effect of hydrogen peroxide 500-fold, suggesting that spore-coat protein has a protective effect against hydrogen peroxide.", "contents": "The effect of hydrogen peroxide on spores of Clostridium bifermentans. The effect of hydrogen peroxide on the germination, colony formation and structure of spores of Clostridium bifermentans was examined. Treatment with 0.35 M-hydrogen peroxide increased the germination rate at 25 degrees C but increasing the temperature or concentration of hydrogen peroxide decreased both the germination rate and colony formation. The presence of Cu2+ increased the lethal effect of hydrogen peroxide on colony formation as much as 3000-fold. Pre-incubation of spores with Cu2+ before treatment with hydrogen peroxide produced a similar increase, but this could be eliminated by washing the spores with dilute spores--apparently from the coat--and treatment with dithiothreitol, which also removes spore-coat protein, increased the lethal effect of hydrogen peroxide 500-fold, suggesting that spore-coat protein has a protective effect against hydrogen peroxide."}
{"id": "PMID:11275", "title": "Molluscum contagiosum -- a defective poxvirus?", "content": "Purified preparations of molluscum contagiosum virus contain a DNA-dependent RNA polymerase (EC 2.7.7.6) with similar but not identical properties to those of the enzyme found in vaccinia virions. The ultraviolet inactivation kinetics of the RNA polymerase from both viruses were similar, displaying fast and slow components. Ultraviolet irradiation destroyed the interfering capacities of molluscum and inactivated vaccinia virions, and the interferon-inducing capacity of molluscum virus slowly and with first-order kinetics. Inactivation studies of the interferon-inducing capacity of vaccinia virus were complicated by cytotoxic effects. Electron microscopical studies showed all stages of virus growth in vaccinia-infected mouse embryo cells; molluscum virus appeared to be degraded in lysosome-like bodies. In preliminary studies, marked changes in cytoplasmic RNA synthesis and in patterns of polypeptide synthesis were found in vaccinia-infected but not in molluscum-infected mouse embryo cells.", "contents": "Molluscum contagiosum -- a defective poxvirus? Purified preparations of molluscum contagiosum virus contain a DNA-dependent RNA polymerase (EC 2.7.7.6) with similar but not identical properties to those of the enzyme found in vaccinia virions. The ultraviolet inactivation kinetics of the RNA polymerase from both viruses were similar, displaying fast and slow components. Ultraviolet irradiation destroyed the interfering capacities of molluscum and inactivated vaccinia virions, and the interferon-inducing capacity of molluscum virus slowly and with first-order kinetics. Inactivation studies of the interferon-inducing capacity of vaccinia virus were complicated by cytotoxic effects. Electron microscopical studies showed all stages of virus growth in vaccinia-infected mouse embryo cells; molluscum virus appeared to be degraded in lysosome-like bodies. In preliminary studies, marked changes in cytoplasmic RNA synthesis and in patterns of polypeptide synthesis were found in vaccinia-infected but not in molluscum-infected mouse embryo cells."}
{"id": "PMID:11276", "title": "Gel filtration of hepatitis B surface antigen: increased size of the native particle.", "content": "The Stokes radius of umpurified hepatitis B antigen (HBSAg) was determined by chromatography on a carefully calibrated Sepharose 4B column. A value of 14-2 nm was found by this procedure, contrasting with a published value of II nm for purified, pepsin-treated HBSAg. Chromatography at pH 3 appeared to reduce the Strokes radius of HBSAg to II nm. Evidence is presented to show that serum proteins adsorbed to HBSAg can be removed with pepsin or acid.", "contents": "Gel filtration of hepatitis B surface antigen: increased size of the native particle. The Stokes radius of umpurified hepatitis B antigen (HBSAg) was determined by chromatography on a carefully calibrated Sepharose 4B column. A value of 14-2 nm was found by this procedure, contrasting with a published value of II nm for purified, pepsin-treated HBSAg. Chromatography at pH 3 appeared to reduce the Strokes radius of HBSAg to II nm. Evidence is presented to show that serum proteins adsorbed to HBSAg can be removed with pepsin or acid."}
{"id": "PMID:11277", "title": "Extrapyramidal effects of neuroleptics.", "content": "A study was conducted on 66 psychiatric inpatients who took major tranquilizers for periods of four to 16 years. The frequency of signs of Parkinsonism and the effects of orphenadrine on these were studied in a double-blind crossover method. Sixty-one per cent of the patients showed signs of Parkinsonism. Female patients and those with organic brain pathology more frequently exhibited Parkinsonism (although the difference was not statistically significant). No correlation was found between duration of treatment and extrapyramidal effects. Of the 40 patients who developed Parkinsonism, 25 responded favourably to orphenadrine, while six (15%) had more marked manifestations on orphenadrine than on placebo.", "contents": "Extrapyramidal effects of neuroleptics. A study was conducted on 66 psychiatric inpatients who took major tranquilizers for periods of four to 16 years. The frequency of signs of Parkinsonism and the effects of orphenadrine on these were studied in a double-blind crossover method. Sixty-one per cent of the patients showed signs of Parkinsonism. Female patients and those with organic brain pathology more frequently exhibited Parkinsonism (although the difference was not statistically significant). No correlation was found between duration of treatment and extrapyramidal effects. Of the 40 patients who developed Parkinsonism, 25 responded favourably to orphenadrine, while six (15%) had more marked manifestations on orphenadrine than on placebo."}
{"id": "PMID:11279", "title": "A health study of employees exposed to vinylidene chloride.", "content": "Previous studies have reported on employee populations exposed coincidentally to vinylidene chloride in copolymer processes using vinyl chloride. The current study examines the mortality and health examination findings of 138 employees exposed to measured levels of vinylidene chloride where vinyl chloride was not used as a copolymer. There were no findings statistically related or individually attributable to vinylidene chloride exposure in this employee population. It is recommended that additional epidemiological studies be undertaken to develop data on chronic exposure to vinylidene chloride.", "contents": "A health study of employees exposed to vinylidene chloride. Previous studies have reported on employee populations exposed coincidentally to vinylidene chloride in copolymer processes using vinyl chloride. The current study examines the mortality and health examination findings of 138 employees exposed to measured levels of vinylidene chloride where vinyl chloride was not used as a copolymer. There were no findings statistically related or individually attributable to vinylidene chloride exposure in this employee population. It is recommended that additional epidemiological studies be undertaken to develop data on chronic exposure to vinylidene chloride."}
{"id": "PMID:11280", "title": "An unusual bilateral pathological fracture.", "content": "An unusual case of a bilateral pathological fracture of the mandible has been presented. The fracture of the right side of the mandible was through an area of bacteroides osteomyelitis and the fracture of the left side of the mandible was through a large cementifying fibroma, which had replaced the left body of the mandible.", "contents": "An unusual bilateral pathological fracture. An unusual case of a bilateral pathological fracture of the mandible has been presented. The fracture of the right side of the mandible was through an area of bacteroides osteomyelitis and the fracture of the left side of the mandible was through a large cementifying fibroma, which had replaced the left body of the mandible."}
{"id": "PMID:11278", "title": "Fetal metachromatic leukodystrophy: pathology, biochemistry and a study of in vitro enzyme replacement in CNS tissue.", "content": "Brain tissue from a fetus with the diagnosis of metachromatic leukodystrophy (MLD) became available at autopsy. Pathologic studies of the CNS showed inclusion bodies within oligodendroglia. The morphology of myelin was normal. Cells and myelin were isolated from the cerebrum; there was an increased level of sulfatide present in both fractions. In vitro studies of enzyme replacement in cultured MLD brain cells indicated that it may be possible to correct the abnormal sulfatide accumulation.", "contents": "Fetal metachromatic leukodystrophy: pathology, biochemistry and a study of in vitro enzyme replacement in CNS tissue. Brain tissue from a fetus with the diagnosis of metachromatic leukodystrophy (MLD) became available at autopsy. Pathologic studies of the CNS showed inclusion bodies within oligodendroglia. The morphology of myelin was normal. Cells and myelin were isolated from the cerebrum; there was an increased level of sulfatide present in both fractions. In vitro studies of enzyme replacement in cultured MLD brain cells indicated that it may be possible to correct the abnormal sulfatide accumulation."}
{"id": "PMID:11284", "title": "Blood acid-base balance at birth in neonates from labors with early and late rupture of membranes.", "content": "The purpose of this study was to determine whether the early artificial rupture of the amniotic membranes performed to shorten the duration of an otherwise normal labor and delivery might have potentially deleterious effects on the fetus that would be reflected in the neonate. In 38 infants delivered at term, acid-base balances and O2 and CO2 pressures were obtained in umbilical arterial and venous blood at birth, prior to the first inspiration. For the purpose of the study the infants were divided into two groups: group I infants were born after a normal labor in which the amniotic membranes were permitted to rupture spontaneously at full cervical dilatation; group II infants were born after a labor in which the membranes were ruptured artificially when cervical dilatation was 4 to 5 cm. There was no evidence of fetal distress, and all infants were vigorous at birth. The pH of umbilical venous blood was greater in the group with late rupture of the membranes (fiftieth percentile [P50] = 7.36) than in those born after early amniotomy (P50 = 7.30) (p less than 0.01). The pH values of umbilical arterial blood were also higher in the group I infants (P50 = 7.31) than in those born after amniotomy (P50 = 7.25)(p less than 0.025). These differences were also observed in the 19 neonates in whom the cord was not encircled around the neck at the time of birth. The PCO2 in umbilical venous blood was less, and the hemoglobin saturation was greater (P less than 0.05) in group I infants than in those of group II. It is possible that the influence of early amniotomy on fetal pH may be deleterious in infants born after high-risk pregnancies in which the uteroplacental circulation is impaired.", "contents": "Blood acid-base balance at birth in neonates from labors with early and late rupture of membranes. The purpose of this study was to determine whether the early artificial rupture of the amniotic membranes performed to shorten the duration of an otherwise normal labor and delivery might have potentially deleterious effects on the fetus that would be reflected in the neonate. In 38 infants delivered at term, acid-base balances and O2 and CO2 pressures were obtained in umbilical arterial and venous blood at birth, prior to the first inspiration. For the purpose of the study the infants were divided into two groups: group I infants were born after a normal labor in which the amniotic membranes were permitted to rupture spontaneously at full cervical dilatation; group II infants were born after a labor in which the membranes were ruptured artificially when cervical dilatation was 4 to 5 cm. There was no evidence of fetal distress, and all infants were vigorous at birth. The pH of umbilical venous blood was greater in the group with late rupture of the membranes (fiftieth percentile [P50] = 7.36) than in those born after early amniotomy (P50 = 7.30) (p less than 0.01). The pH values of umbilical arterial blood were also higher in the group I infants (P50 = 7.31) than in those born after amniotomy (P50 = 7.25)(p less than 0.025). These differences were also observed in the 19 neonates in whom the cord was not encircled around the neck at the time of birth. The PCO2 in umbilical venous blood was less, and the hemoglobin saturation was greater (P less than 0.05) in group I infants than in those of group II. It is possible that the influence of early amniotomy on fetal pH may be deleterious in infants born after high-risk pregnancies in which the uteroplacental circulation is impaired."}
{"id": "PMID:11285", "title": "The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method.", "content": "A method is described for the rapid determination of phenothiazine drugs in a wide variety of pharmaceutical preparations. The drugs are determined by a difference spectrophotometric technique based upon the absorbance of the sulphoxide derivative of the drug relative to the absorbance of a solution of the underivatized drug. The sulphoxide derivatives are formed rapidly and quantitatively at room temperature by the addition of a solution of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid on standing. The difference absorbance of the solutions is proportional to the concentration of the phenothiazine drug in the preparation and is specific for the intact drug in the presence of oxidative and photochemical decomposition products, colouring and flavouring agents, excipients and most co-formulated drugs.", "contents": "The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method. A method is described for the rapid determination of phenothiazine drugs in a wide variety of pharmaceutical preparations. The drugs are determined by a difference spectrophotometric technique based upon the absorbance of the sulphoxide derivative of the drug relative to the absorbance of a solution of the underivatized drug. The sulphoxide derivatives are formed rapidly and quantitatively at room temperature by the addition of a solution of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid on standing. The difference absorbance of the solutions is proportional to the concentration of the phenothiazine drug in the preparation and is specific for the intact drug in the presence of oxidative and photochemical decomposition products, colouring and flavouring agents, excipients and most co-formulated drugs."}
{"id": "PMID:11286", "title": "The influence of casting solvent composition on structure and permeability of acrylic-methacrylic ester copolymer films.", "content": "Decrease in the solvation of polymer by inclusion of ethanol in the acetone casting solution resulted in greater permeability to urea of cast acrylate-methacrylate film. The greater permeability was accompanied particularly by a decrease in pore size and increase in pore number, despite the absence of change in pore area. A decrease in cohesiveness in the film was suggested by the decrease in tortuosity of the pores as seen by scanning electron microscopy; also, water uptake was increased when the film was cast from an ethanolic solution. The results support the view that, in practice, the composition of the solvent, by its effect on microstructure, can affect the function of the film cast from it.", "contents": "The influence of casting solvent composition on structure and permeability of acrylic-methacrylic ester copolymer films. Decrease in the solvation of polymer by inclusion of ethanol in the acetone casting solution resulted in greater permeability to urea of cast acrylate-methacrylate film. The greater permeability was accompanied particularly by a decrease in pore size and increase in pore number, despite the absence of change in pore area. A decrease in cohesiveness in the film was suggested by the decrease in tortuosity of the pores as seen by scanning electron microscopy; also, water uptake was increased when the film was cast from an ethanolic solution. The results support the view that, in practice, the composition of the solvent, by its effect on microstructure, can affect the function of the film cast from it."}
{"id": "PMID:11287", "title": "The granulation of binary mixtures: the effects of the composition of the granulating solution and the initial particle size of one component on granule properties.", "content": "The effect of total solvent volume and the presence of dissolved material (other than binder) in the granulating solution, on the properties of granules prepared from lactose: boric acid mixtures has been studied. The total volume of binder solution available to powder mixtures during massing determines the ultimate average size of granules produced. Part-dissolution of powders being granulated contributes significantly to the average granule size by increasing the total solution volume and reducing the amount of powder to be wetted. Although the amount of PVP (binder) dissolved in the granulating solution contributed very little to granule size at the concentration examined, the combined effect of total volume of solution and amount of PVP present in the granulating solution determines granule strength and porosity. The effect of the initial particle size of lactose in a binary mixture with boric acid differs from its effect reported for single component systems.", "contents": "The granulation of binary mixtures: the effects of the composition of the granulating solution and the initial particle size of one component on granule properties. The effect of total solvent volume and the presence of dissolved material (other than binder) in the granulating solution, on the properties of granules prepared from lactose: boric acid mixtures has been studied. The total volume of binder solution available to powder mixtures during massing determines the ultimate average size of granules produced. Part-dissolution of powders being granulated contributes significantly to the average granule size by increasing the total solution volume and reducing the amount of powder to be wetted. Although the amount of PVP (binder) dissolved in the granulating solution contributed very little to granule size at the concentration examined, the combined effect of total volume of solution and amount of PVP present in the granulating solution determines granule strength and porosity. The effect of the initial particle size of lactose in a binary mixture with boric acid differs from its effect reported for single component systems."}
{"id": "PMID:11288", "title": "A thin-layer chromatographic procedure for the assay of labelled noradrenaline and its metabolites in tissues and in incubation medium.", "content": "A method for the extraction, separation and quantitative determination of [3H]noradrenaline [3H-NA] and its five major metabolites has been devised using thin layer chromatography. This procedure was used to study the pattern of 3H-NA and its metabolites in the total radioactivity of the tissues and that released spontaneously from the rat isolated vas deferens. Whereas in tissues 3H-NA represented almost all of the total radioactivity (94-8+/-0.47%), in the samples of spontaneous outflow it represented only 16-8+/-2.1%. The rest was mostly accounted for by the five metabolites, primarily 3H-DOPEG and 3H-MOPEG. These findings show that in the rat vas deferens 3H-NA is preferentially metabolized via the two glycol derivatives, i.e. 3H-DOPEG and 3H-MOPEG.", "contents": "A thin-layer chromatographic procedure for the assay of labelled noradrenaline and its metabolites in tissues and in incubation medium. A method for the extraction, separation and quantitative determination of [3H]noradrenaline [3H-NA] and its five major metabolites has been devised using thin layer chromatography. This procedure was used to study the pattern of 3H-NA and its metabolites in the total radioactivity of the tissues and that released spontaneously from the rat isolated vas deferens. Whereas in tissues 3H-NA represented almost all of the total radioactivity (94-8+/-0.47%), in the samples of spontaneous outflow it represented only 16-8+/-2.1%. The rest was mostly accounted for by the five metabolites, primarily 3H-DOPEG and 3H-MOPEG. These findings show that in the rat vas deferens 3H-NA is preferentially metabolized via the two glycol derivatives, i.e. 3H-DOPEG and 3H-MOPEG."}
{"id": "PMID:11289", "title": "In vitro metabolism of 1-phenyl-2-(n-propylamino) propane (N-propylamphetamine) by rat liver homogenates.", "content": "In vitro incubation of (+/-)-N-(n-propyl)amphetamine (NPA) with the 12000 g supernatant fraction of rat liver hmogenate resulted in the formation of two N-oxygenated products identified as N-hydroxy-1-phenyl-2(n-propylamino)propane and N-[(1-methyl-2-phenyl) ethyl]-1-propanamine N-oxide by g.l.c., g.l.c.-m.s. and t.l.c. Amphetamine, phenylacetone,...", "contents": "In vitro metabolism of 1-phenyl-2-(n-propylamino) propane (N-propylamphetamine) by rat liver homogenates. In vitro incubation of (+/-)-N-(n-propyl)amphetamine (NPA) with the 12000 g supernatant fraction of rat liver hmogenate resulted in the formation of two N-oxygenated products identified as N-hydroxy-1-phenyl-2(n-propylamino)propane and N-[(1-methyl-2-phenyl) ethyl]-1-propanamine N-oxide by g.l.c., g.l.c.-m.s. and t.l.c. Amphetamine, phenylacetone,..."}
{"id": "PMID:11290", "title": "A proposed mechanism for the biphasic vasoconstrictor responses to 5-hydroxytryptamine and methysergide in the rabbit ear artery.", "content": "Rabbit ear arteries were isolated and perfused at a constant flow rate so that the perfusate flowed into the fluid bathing the adventitial surface of the artery. Submaximal doses of intraluminally applied noradrenaline injected as a bolus into the perfusion fluid produced transient monophasic vascoconstrictor responses. In contrast, similarly administered 5-hydroxytryptamine (5-HT) or methysergide caused prolonged biphasic vascoconstrictor responses. The extraluminal/intraluminal potency ratios for noradrenaline, 5-HT and methysergide were 230, 15 and 6 respectively, which indicates that 5-HT methysergide are relatively more potent when administered extraluminally than noradrenaline. Cocaine (3-0 X 10(-5) mol litre-1) markedly increased the potency of extraluminally administered noradrenaline and converted the monophasic responses produced by noradrenaline to biphasic responses. It is concluded that under the experimental conditions used 5-HT and methysergide produced biphasic responses by an action on the medial smooth muscle firstly via the intraluminal surface and secondly an additional direct action via the adventitial surface. Noradrenaline's extraluminal potency is low because of its neuronal uptake and hence the responses are normally monophasic.", "contents": "A proposed mechanism for the biphasic vasoconstrictor responses to 5-hydroxytryptamine and methysergide in the rabbit ear artery. Rabbit ear arteries were isolated and perfused at a constant flow rate so that the perfusate flowed into the fluid bathing the adventitial surface of the artery. Submaximal doses of intraluminally applied noradrenaline injected as a bolus into the perfusion fluid produced transient monophasic vascoconstrictor responses. In contrast, similarly administered 5-hydroxytryptamine (5-HT) or methysergide caused prolonged biphasic vascoconstrictor responses. The extraluminal/intraluminal potency ratios for noradrenaline, 5-HT and methysergide were 230, 15 and 6 respectively, which indicates that 5-HT methysergide are relatively more potent when administered extraluminally than noradrenaline. Cocaine (3-0 X 10(-5) mol litre-1) markedly increased the potency of extraluminally administered noradrenaline and converted the monophasic responses produced by noradrenaline to biphasic responses. It is concluded that under the experimental conditions used 5-HT and methysergide produced biphasic responses by an action on the medial smooth muscle firstly via the intraluminal surface and secondly an additional direct action via the adventitial surface. Noradrenaline's extraluminal potency is low because of its neuronal uptake and hence the responses are normally monophasic."}
{"id": "PMID:11291", "title": "A comparison of the effects of morphine and pethidine upon body temperature and the reversal of reserpine's effects upon body temperature in the mouse.", "content": "The effects of morphine and pethidine upon body temperature and upon the reversal of reserpine hypothermia in the mouse were investigated. Both morphine and pethidine produced a dose-dependent fall in body temperature, that of morphine being totally antagonized by nalorphine and partially by naloxone, while that of pethidine was antagonised by naloxone and enhanced by nalorphine. Both drugs reversed reserpine-induced hypothermia. The reversal by morphine, but not by pethidine, was partially antagonized by naloxone. Adrenalectomy prevented the reversal of reserpine hypothermia by pethidine but morphine produced a partial reversal. Ganglion blockade and alpha-and beta-blockade all prevented reversal of reserpine hypothermia by both drugs. The results are discussed with regard to differences between pethidine and morphine and possible involvement of opiate receptors.", "contents": "A comparison of the effects of morphine and pethidine upon body temperature and the reversal of reserpine's effects upon body temperature in the mouse. The effects of morphine and pethidine upon body temperature and upon the reversal of reserpine hypothermia in the mouse were investigated. Both morphine and pethidine produced a dose-dependent fall in body temperature, that of morphine being totally antagonized by nalorphine and partially by naloxone, while that of pethidine was antagonised by naloxone and enhanced by nalorphine. Both drugs reversed reserpine-induced hypothermia. The reversal by morphine, but not by pethidine, was partially antagonized by naloxone. Adrenalectomy prevented the reversal of reserpine hypothermia by pethidine but morphine produced a partial reversal. Ganglion blockade and alpha-and beta-blockade all prevented reversal of reserpine hypothermia by both drugs. The results are discussed with regard to differences between pethidine and morphine and possible involvement of opiate receptors."}
{"id": "PMID:11292", "title": "Enhancement of ethonol-induced withdrawal convulsions by blockade of 5-hydroxytryptamine receptors.", "content": "Male Swiss-Webster mice were made physically dependent on ethanol using the ethanol vapour inhalation technique. Animals pretreated with methysergide, a known 5-hydroxytryptamine receptor blocking agent, had significantly greater alcohol-induced withdrawal convulsions than saline pretreated controls. These findings suggest that the reduction of 5-HT at receptor sites may result in the augmentation of the withdrawal convulsions.", "contents": "Enhancement of ethonol-induced withdrawal convulsions by blockade of 5-hydroxytryptamine receptors. Male Swiss-Webster mice were made physically dependent on ethanol using the ethanol vapour inhalation technique. Animals pretreated with methysergide, a known 5-hydroxytryptamine receptor blocking agent, had significantly greater alcohol-induced withdrawal convulsions than saline pretreated controls. These findings suggest that the reduction of 5-HT at receptor sites may result in the augmentation of the withdrawal convulsions."}
{"id": "PMID:11306", "title": "Dioxygenated metabolites of cannabidiol formed by rat liver.", "content": "The metabolism of cannabidiol (CBD) was studied in vitro using a 10 000 g supernatant from rat liver. After removal of unchanged CBD and its monohydroxylated metabolites, a polar fraction remained from which ten dioxygenated metabolites were isolated. Mass spectrometry and nuclear magnetic resonance spectroscopy were used to identify the following metabolites: 6,7-dihydroxy-CBD, 1 inch,7-dihydroxy-CBD, 3 inch,7-dihydroxy-CBD, 4 inch,7-dihydroxy-CBD, 5 inch,7-dihydroxy-CBD, 2 inch,6-dihydroxy-CBD, 3 inch,6beta-dihydroxy-CBD, 4 inch, 6beta-dihydroxy-CBD (tentative), 3 inch-hydroxy-6-oxo-CBD, and 4 inch-hydroxy-6-oxo-CBD. The abundance of isolated dihydroxy metabolites reflected the quantity of monohydroxy metabolites that was previously found. In both series, 7-hydroxylation occurred to the greatest extent. Side chain hydroxylation occurred predominantly at C-4 inch and to a lesser degree at C-3 inch. Trace amounts of metabolites were hydroxylated at C-1 inch,-2 inch, or 5 inch.", "contents": "Dioxygenated metabolites of cannabidiol formed by rat liver. The metabolism of cannabidiol (CBD) was studied in vitro using a 10 000 g supernatant from rat liver. After removal of unchanged CBD and its monohydroxylated metabolites, a polar fraction remained from which ten dioxygenated metabolites were isolated. Mass spectrometry and nuclear magnetic resonance spectroscopy were used to identify the following metabolites: 6,7-dihydroxy-CBD, 1 inch,7-dihydroxy-CBD, 3 inch,7-dihydroxy-CBD, 4 inch,7-dihydroxy-CBD, 5 inch,7-dihydroxy-CBD, 2 inch,6-dihydroxy-CBD, 3 inch,6beta-dihydroxy-CBD, 4 inch, 6beta-dihydroxy-CBD (tentative), 3 inch-hydroxy-6-oxo-CBD, and 4 inch-hydroxy-6-oxo-CBD. The abundance of isolated dihydroxy metabolites reflected the quantity of monohydroxy metabolites that was previously found. In both series, 7-hydroxylation occurred to the greatest extent. Side chain hydroxylation occurred predominantly at C-4 inch and to a lesser degree at C-3 inch. Trace amounts of metabolites were hydroxylated at C-1 inch,-2 inch, or 5 inch."}
{"id": "PMID:11307", "title": "Effects of various diuretic agents in the mouse.", "content": "Diuretic effects of seven orally-acting diuretic agents have been examined in the mouse. The following compounds, examples of various types of orally active compound available, produced their characteristic diuretic effects: bendrofluazide, frusemide, ethacrynic acid, acetazolamide, triamterene, aminophylline and Su 15049A. The diuretic effects of the various agents were demonstrated under both water and saline-loading conditions. After allowing for differences in baseline sodium excretion, all diuretics except acetazolamide caused a further enhancement of sodium excretion after saline-loading compared with water-loading tests. The mouse possesses several advantages over the more commonly used rat since the range of diuretic responsiveness is greater. These results suggest that the mouse is a suitable species for diuretic testing.", "contents": "Effects of various diuretic agents in the mouse. Diuretic effects of seven orally-acting diuretic agents have been examined in the mouse. The following compounds, examples of various types of orally active compound available, produced their characteristic diuretic effects: bendrofluazide, frusemide, ethacrynic acid, acetazolamide, triamterene, aminophylline and Su 15049A. The diuretic effects of the various agents were demonstrated under both water and saline-loading conditions. After allowing for differences in baseline sodium excretion, all diuretics except acetazolamide caused a further enhancement of sodium excretion after saline-loading compared with water-loading tests. The mouse possesses several advantages over the more commonly used rat since the range of diuretic responsiveness is greater. These results suggest that the mouse is a suitable species for diuretic testing."}
{"id": "PMID:11308", "title": "Effects of animal maturity on smooth muscle and blood pressure responses to prostaglandins E2 and F2alpha.", "content": "The effects of prostaglandins E2 (PGE2) and F2alpha (PGF2-alpha) on muscle strips from mature and immature rats and guinea-pigs and on rat blood pressure were investigated in the presence of atropine. The colon and stomach strips from immature rats were equally responsive to PGE 2 and PGF2alpha where mature colons were significantly more sensitive to PGF2ALPHA AND MATURE STOMACH STRIPS SIGNIFICANTLY MORE SENSITIVE TO PGE2. On the ileum from immature guinea-pigs the maximum responses to PGE2 and PGF2alpha were 16 and 8% of the histamine maximum respectively. The corresponding figures on the mature ileum were 86 and 75%. Whereas PGE2 was only twice as active as PGF2alpha on immature ilea, it was ten times more active than PGF2alpha on mature muscles. On blood pressure PGF2alpha and PGE2 were both hypotensive in immature rats whereas PGE2 was hypotensive and PGF2alpha hypertensive in mature rats. The results suggest that as the animal gets older, receptors for prostaglandins became increasingly differentiated.", "contents": "Effects of animal maturity on smooth muscle and blood pressure responses to prostaglandins E2 and F2alpha. The effects of prostaglandins E2 (PGE2) and F2alpha (PGF2-alpha) on muscle strips from mature and immature rats and guinea-pigs and on rat blood pressure were investigated in the presence of atropine. The colon and stomach strips from immature rats were equally responsive to PGE 2 and PGF2alpha where mature colons were significantly more sensitive to PGF2ALPHA AND MATURE STOMACH STRIPS SIGNIFICANTLY MORE SENSITIVE TO PGE2. On the ileum from immature guinea-pigs the maximum responses to PGE2 and PGF2alpha were 16 and 8% of the histamine maximum respectively. The corresponding figures on the mature ileum were 86 and 75%. Whereas PGE2 was only twice as active as PGF2alpha on immature ilea, it was ten times more active than PGF2alpha on mature muscles. On blood pressure PGF2alpha and PGE2 were both hypotensive in immature rats whereas PGE2 was hypotensive and PGF2alpha hypertensive in mature rats. The results suggest that as the animal gets older, receptors for prostaglandins became increasingly differentiated."}
{"id": "PMID:11309", "title": "Actions of the muscle relaxant chandonium iodide on guinea-pig ileum and vas deferens preparations.", "content": "The effects of the newly synthesized neuromuscular blocking agent, chandonium iodide (17a-methyl-3beta-pyrrolidino-17a-aza-D-homo-5-androstene dimethiodide) have been investigated on guinea-pig isolated ileum and vas deferens preparations. On the ileum, chandonium (0-1-10-0 mug ml(-1); 1-6 X 10(-7) M-1-6 X 10(-5) M) had weak muscarinic receptor blocking action (pA2 is 5-7), but no antihistamine properties at the concentration tested. No evidence for anticholinesterase actions was found. On the vas deferens, chandonium (10-50 mug ml(-1); 1-6-8-1 X 10(-5) M) potentiated responses to exogenous noradrenaline; responses to electrical stimulation were potentiated only in the presence of 50 mug ml(-1) chandonium. No adrenoceptor or adrenergic neuron blockade was found. The results provide evidence that chandonium acts selectively at acetylcholine receptors and that it is more active as a nicotinic receptor antagonist than as a muscarinic receptor antagonist.", "contents": "Actions of the muscle relaxant chandonium iodide on guinea-pig ileum and vas deferens preparations. The effects of the newly synthesized neuromuscular blocking agent, chandonium iodide (17a-methyl-3beta-pyrrolidino-17a-aza-D-homo-5-androstene dimethiodide) have been investigated on guinea-pig isolated ileum and vas deferens preparations. On the ileum, chandonium (0-1-10-0 mug ml(-1); 1-6 X 10(-7) M-1-6 X 10(-5) M) had weak muscarinic receptor blocking action (pA2 is 5-7), but no antihistamine properties at the concentration tested. No evidence for anticholinesterase actions was found. On the vas deferens, chandonium (10-50 mug ml(-1); 1-6-8-1 X 10(-5) M) potentiated responses to exogenous noradrenaline; responses to electrical stimulation were potentiated only in the presence of 50 mug ml(-1) chandonium. No adrenoceptor or adrenergic neuron blockade was found. The results provide evidence that chandonium acts selectively at acetylcholine receptors and that it is more active as a nicotinic receptor antagonist than as a muscarinic receptor antagonist."}
{"id": "PMID:11310", "title": "A comparative study of the effect of bile salts on the absorption of quinalbarbitone sodium in goldfish.", "content": "The goldfish has been used as a model membrane to estimate the absorption of quinalbarbitone sodium by measurement of overturn time. The effect of sodium cholate, sodium deoxycholate, sodium chenodeoxycholate and sodium taurodeoxycholate on the quinalbarbitone-induced overturn time has been investigated and differences in capacity to promote absorption have been demonstrated. These differences could not be attributed to variations in solubility or partitioning of the drug within the membrane by the bile salts or to the relative hydrophobicity of each molecule. It is suggested that the bile salts must in someway affect the integrity of the goldfish membrane rendering it more permeable to quinalbarbitone sodium.", "contents": "A comparative study of the effect of bile salts on the absorption of quinalbarbitone sodium in goldfish. The goldfish has been used as a model membrane to estimate the absorption of quinalbarbitone sodium by measurement of overturn time. The effect of sodium cholate, sodium deoxycholate, sodium chenodeoxycholate and sodium taurodeoxycholate on the quinalbarbitone-induced overturn time has been investigated and differences in capacity to promote absorption have been demonstrated. These differences could not be attributed to variations in solubility or partitioning of the drug within the membrane by the bile salts or to the relative hydrophobicity of each molecule. It is suggested that the bile salts must in someway affect the integrity of the goldfish membrane rendering it more permeable to quinalbarbitone sodium."}
{"id": "PMID:11311", "title": "Gels in soap stabilized emulsions.", "content": "In some soap stabilized liquid paraffin emulsions a correlation has been found between emulsion type and the contact angle of the soap gel (the stabilizing agent) at the o/w interface. Two unrelated series of emulsions have been prepared, one series being stabilized by magnesium oleate gels and the other series by ammonium oleate gels. The soap gels were prepared by double decomposition and suppression of ionization respectively. Unlike the magnesium oleate system no inversion to w/o emulsions occurred with the ammonium oleate series. This dissimilarity is predicted from differences in the contact angles of the soap gels at the o/w interface.", "contents": "Gels in soap stabilized emulsions. In some soap stabilized liquid paraffin emulsions a correlation has been found between emulsion type and the contact angle of the soap gel (the stabilizing agent) at the o/w interface. Two unrelated series of emulsions have been prepared, one series being stabilized by magnesium oleate gels and the other series by ammonium oleate gels. The soap gels were prepared by double decomposition and suppression of ionization respectively. Unlike the magnesium oleate system no inversion to w/o emulsions occurred with the ammonium oleate series. This dissimilarity is predicted from differences in the contact angles of the soap gels at the o/w interface."}
{"id": "PMID:11312", "title": "The effect of waxes, hydrolysed gelatin and moisture on the compression characteristics of paracetamol and phenacetin.", "content": "Stearic acid or hard paraffin added to crystals of paracetamol and phenacetin reduced capping of tablets prepared by direct compression but did not produce acceptable tablets because the inter-particular bonds were very weak. The pressure cycle that can be constructed form the measurement of the axial pressure and the corresponding die wall pressures offers information that is useful in the formulation of the tablets. The behaviour of paracetamol or phenacetin and their mixtures with gelatin hydrolysate or water or both shows a similarity to a Mohr body and it appears that the maximum die wall pressure is affected by the particle size of the material compressed and also by the additives present. Good transmission of radial force implies that the material can be initially consolidated, but alone it does not indicate that the tablet formed is physically stable. When the tablet formed remains coherent after the axial pressure is removed the residual die wall pressure remains high. Measurement of the residual die wall pressure might therefore be a useful indicator for identifying satisfactory formulations of substances that cap readily. Hydrolysed gelatin or water or both together produced paracetamol and phenacetin mixtures with satisfacotry compression characteristics.", "contents": "The effect of waxes, hydrolysed gelatin and moisture on the compression characteristics of paracetamol and phenacetin. Stearic acid or hard paraffin added to crystals of paracetamol and phenacetin reduced capping of tablets prepared by direct compression but did not produce acceptable tablets because the inter-particular bonds were very weak. The pressure cycle that can be constructed form the measurement of the axial pressure and the corresponding die wall pressures offers information that is useful in the formulation of the tablets. The behaviour of paracetamol or phenacetin and their mixtures with gelatin hydrolysate or water or both shows a similarity to a Mohr body and it appears that the maximum die wall pressure is affected by the particle size of the material compressed and also by the additives present. Good transmission of radial force implies that the material can be initially consolidated, but alone it does not indicate that the tablet formed is physically stable. When the tablet formed remains coherent after the axial pressure is removed the residual die wall pressure remains high. Measurement of the residual die wall pressure might therefore be a useful indicator for identifying satisfactory formulations of substances that cap readily. Hydrolysed gelatin or water or both together produced paracetamol and phenacetin mixtures with satisfacotry compression characteristics."}
{"id": "PMID:11313", "title": "Effect of disintegrant type upon the relationship between compressional pressure and dissolution efficiency.", "content": "Four tablet disintegrants: a relatively insoluble sodium carboxymethyl cellulose, casein formaldehyde, calcium carboxymethyl cellulose and a cross-linked polyvinylpyrrolidone have been evaluated. Three widely used disintegrants, sodium carboxymethyl cellulose, sodium starch glycolate and a cation exchange resin were included for comparison. The effect of compressional pressure on the disintegration and dissolution behaviours of a soluble and an insoluble system containing different disintegrants were examined. The results show that disintegrant type can have a pronounced effect upon the relationship between compressional pressure and dissolution efficiency. The significance of this relationship is discussed in terms of the properties of disintegrants and the differing mechanisms by which they act.", "contents": "Effect of disintegrant type upon the relationship between compressional pressure and dissolution efficiency. Four tablet disintegrants: a relatively insoluble sodium carboxymethyl cellulose, casein formaldehyde, calcium carboxymethyl cellulose and a cross-linked polyvinylpyrrolidone have been evaluated. Three widely used disintegrants, sodium carboxymethyl cellulose, sodium starch glycolate and a cation exchange resin were included for comparison. The effect of compressional pressure on the disintegration and dissolution behaviours of a soluble and an insoluble system containing different disintegrants were examined. The results show that disintegrant type can have a pronounced effect upon the relationship between compressional pressure and dissolution efficiency. The significance of this relationship is discussed in terms of the properties of disintegrants and the differing mechanisms by which they act."}
{"id": "PMID:11314", "title": "Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol.", "content": "Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17 beta-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism.", "contents": "Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol. Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17 beta-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism."}
{"id": "PMID:11330", "title": "Comparative stability of cephalosporins in aqueous solution: kinetics and mechanisms of degradation.", "content": "The acidic, neutral, and alkaline degradations of six therapeutically useful cephalosporins (cephalothin, cephaloridine, cephaloglycin, cephalexin, cephradine, and cefazolin), 7-amino-cephalosporanic acid, 7-aminodeacetoxycephalosporanic acid, and some 7-substituted derivatives were followed by high-pressure liquid chromatographic, UV spectrometric, iodometric, and hydroxamic acid assays. The pH-rate profiles were determined at 35 degrees and mu = 0.5. The acidic degradation pathway for the 3-acetoxymethyl and 3-pyridinylmethyl derivatives was the specific hydrogen-ion-catalyzed hydrolysis of the beta-lactam bonds. The beta-lactam hydrolyses of these antibiotics exhibited half-lives of about 25 hr at pH 1.0 and 35 degrees. The acetyl functions of 3-acetoxymethylcephalosporins were hydrolyzed eight times faster than their beta-lactam moieties to yield the corresponding deacetyl intermediates, which were rapidly converted to the lactones. Deacetoxycephalosporins were fairly acid stable; e.g., cephalexin and cephradine were about 25 times more stable than cephalothin, cephaloridine, and cephaloglycin and about 180 times more stable than ampicillin at pH 1.0. In the neutral degradation of 3-acetoxymethyl compounds, the competitive reactions of the direct water attack and intramolecular catalysis by the side-chain amido upon the beta-lactams were proposed. The pH-rate profiles near pH 8 for cephaloglycin, cephalexin, and cephradine could be explained by the intramolecular-nucleophilic attack of the side-chain alpha-amino group upon the beta-lactam carbonyls to produce diketopiperazine-type compounds. The reactivity of the cephalosporins in the hydroxideion-catalyzed degradation was influenced significantly by the C-3 methylene substituents.", "contents": "Comparative stability of cephalosporins in aqueous solution: kinetics and mechanisms of degradation. The acidic, neutral, and alkaline degradations of six therapeutically useful cephalosporins (cephalothin, cephaloridine, cephaloglycin, cephalexin, cephradine, and cefazolin), 7-amino-cephalosporanic acid, 7-aminodeacetoxycephalosporanic acid, and some 7-substituted derivatives were followed by high-pressure liquid chromatographic, UV spectrometric, iodometric, and hydroxamic acid assays. The pH-rate profiles were determined at 35 degrees and mu = 0.5. The acidic degradation pathway for the 3-acetoxymethyl and 3-pyridinylmethyl derivatives was the specific hydrogen-ion-catalyzed hydrolysis of the beta-lactam bonds. The beta-lactam hydrolyses of these antibiotics exhibited half-lives of about 25 hr at pH 1.0 and 35 degrees. The acetyl functions of 3-acetoxymethylcephalosporins were hydrolyzed eight times faster than their beta-lactam moieties to yield the corresponding deacetyl intermediates, which were rapidly converted to the lactones. Deacetoxycephalosporins were fairly acid stable; e.g., cephalexin and cephradine were about 25 times more stable than cephalothin, cephaloridine, and cephaloglycin and about 180 times more stable than ampicillin at pH 1.0. In the neutral degradation of 3-acetoxymethyl compounds, the competitive reactions of the direct water attack and intramolecular catalysis by the side-chain amido upon the beta-lactams were proposed. The pH-rate profiles near pH 8 for cephaloglycin, cephalexin, and cephradine could be explained by the intramolecular-nucleophilic attack of the side-chain alpha-amino group upon the beta-lactam carbonyls to produce diketopiperazine-type compounds. The reactivity of the cephalosporins in the hydroxideion-catalyzed degradation was influenced significantly by the C-3 methylene substituents."}
{"id": "PMID:11331", "title": "Simultaneous semiautomated assay of pyrrobutamine phosphate, cyclopentamine hydrochloride, and methapyrilene hydrochloride in pharmaceutical mixtures.", "content": "Antihistamine preparations containing methapyrilene hydrochloride, pyrrobutamine phosphate, and cyclopentamine hydrochloride were assayed by introducing an aqueous sample solution into the appropriate automated system. Methapyrilene hydrochloride was determined by UV spectrophotometry. Pyrrobutamine phosphate was extracted as an ion-pair and quantitated colorimetrically by forming the bromcresol purple acid-dye complex. Cyclopentamine hydrochloride was determined colorimetrically by using the copper dithiocarbamate reaction for secondary amines.", "contents": "Simultaneous semiautomated assay of pyrrobutamine phosphate, cyclopentamine hydrochloride, and methapyrilene hydrochloride in pharmaceutical mixtures. Antihistamine preparations containing methapyrilene hydrochloride, pyrrobutamine phosphate, and cyclopentamine hydrochloride were assayed by introducing an aqueous sample solution into the appropriate automated system. Methapyrilene hydrochloride was determined by UV spectrophotometry. Pyrrobutamine phosphate was extracted as an ion-pair and quantitated colorimetrically by forming the bromcresol purple acid-dye complex. Cyclopentamine hydrochloride was determined colorimetrically by using the copper dithiocarbamate reaction for secondary amines."}
{"id": "PMID:11332", "title": "Effect of polymers on dissolution from drug suspensions.", "content": "The effect of three viscosity grades of methylcellulose on the dissolution-dialysis rate of nitrofurantoin suspensions was investigated using a cell designed to provide a large surface area for dialysis. Apparent dialytic rate constants of drug dispersions and solutions were measured in 0.1 N HC1 and in pH 7.4 buffer. Samples containing methylcellulose had lower rates of dialysis, with the lowest rate being observed for samples in which the polymer was used as the suspending agent. The reduced rate of dialysis of the drug suspension containing methylcellulose is thought to be due to complexation of the drug in solution with the polymer as well as formation of microscopic regions of high viscosity surrounding the undissolved drug particles leading to a reduction in the dissolution rate of the drug. An empirical relationship was obtained to enable the estimation of the effective drug concentration in the dissolution chamber for drug dispersions. The method is based on utilizing dialysis rate data of drug solutions. This relationship could be used for comparing suspension formulations in terms of the amount of drug available for dialysis.", "contents": "Effect of polymers on dissolution from drug suspensions. The effect of three viscosity grades of methylcellulose on the dissolution-dialysis rate of nitrofurantoin suspensions was investigated using a cell designed to provide a large surface area for dialysis. Apparent dialytic rate constants of drug dispersions and solutions were measured in 0.1 N HC1 and in pH 7.4 buffer. Samples containing methylcellulose had lower rates of dialysis, with the lowest rate being observed for samples in which the polymer was used as the suspending agent. The reduced rate of dialysis of the drug suspension containing methylcellulose is thought to be due to complexation of the drug in solution with the polymer as well as formation of microscopic regions of high viscosity surrounding the undissolved drug particles leading to a reduction in the dissolution rate of the drug. An empirical relationship was obtained to enable the estimation of the effective drug concentration in the dissolution chamber for drug dispersions. The method is based on utilizing dialysis rate data of drug solutions. This relationship could be used for comparing suspension formulations in terms of the amount of drug available for dialysis."}
{"id": "PMID:11333", "title": "Biotransformation of drugs: quantitative structure-activity relationships for barbiturates, tertiary amines, and substituted imidazoles.", "content": "When using free energy-related physicochemical parameters, stimulation of NADPH oxidation by barbiturates and the N-oxidation of tertiary amines was found to be primarily dependent upon the lipophilic character of the substrates as measured by log P, where P is the partition coefficient from either 1-octanol-water or corn oil-water solvent systems. In contrast, the inhibition of epoxidation of aldrin by a series of substituted imidazoles appears to be much more dependent on electronic (sigma) and steric (Es) effects of the inhibitors.", "contents": "Biotransformation of drugs: quantitative structure-activity relationships for barbiturates, tertiary amines, and substituted imidazoles. When using free energy-related physicochemical parameters, stimulation of NADPH oxidation by barbiturates and the N-oxidation of tertiary amines was found to be primarily dependent upon the lipophilic character of the substrates as measured by log P, where P is the partition coefficient from either 1-octanol-water or corn oil-water solvent systems. In contrast, the inhibition of epoxidation of aldrin by a series of substituted imidazoles appears to be much more dependent on electronic (sigma) and steric (Es) effects of the inhibitors."}
{"id": "PMID:11334", "title": "Effect of topically applied pilocarpine on tear film pH.", "content": "Changes in tear film pH were observed during the 1st hr after instillation of pilocarpine in various dosage forms to the rabbit eye. In anesthetized rabbits, with periodic blinking induced electrically, commercial formulations of pilocarpine salts applied as drops or a spray acutely lowered tear film pH by 1.1-1.6 pH units. The pH remained below pretreatment levels for 45-greater than 60 min after instillation. Pilocarpine base, administered continuously at the rates of 20 or 80 mug/hr from ocular therapeutic systems, had little or no effect on tear film pH in this same animal preparation. The reduction in tear film pH produced by pilocarpine eyedrops or spray solution is attributable to the acid pH and buffer capacity of these solutions. Delivery of pilocarpine base without pH change was achieved with ocular therapeutic systems, because the drug (pKa = 7.07) was delivered free, or virtually so, of excipients. These observed differences in tear film pH after application may partially explain the four- to eightfold reduction in total effective pilocarpine dose with ocular therapeutic systems compared to eyedrops or spray, since the cornea is less permeable to ionized than to unionized molecules.", "contents": "Effect of topically applied pilocarpine on tear film pH. Changes in tear film pH were observed during the 1st hr after instillation of pilocarpine in various dosage forms to the rabbit eye. In anesthetized rabbits, with periodic blinking induced electrically, commercial formulations of pilocarpine salts applied as drops or a spray acutely lowered tear film pH by 1.1-1.6 pH units. The pH remained below pretreatment levels for 45-greater than 60 min after instillation. Pilocarpine base, administered continuously at the rates of 20 or 80 mug/hr from ocular therapeutic systems, had little or no effect on tear film pH in this same animal preparation. The reduction in tear film pH produced by pilocarpine eyedrops or spray solution is attributable to the acid pH and buffer capacity of these solutions. Delivery of pilocarpine base without pH change was achieved with ocular therapeutic systems, because the drug (pKa = 7.07) was delivered free, or virtually so, of excipients. These observed differences in tear film pH after application may partially explain the four- to eightfold reduction in total effective pilocarpine dose with ocular therapeutic systems compared to eyedrops or spray, since the cornea is less permeable to ionized than to unionized molecules."}
{"id": "PMID:11335", "title": "Effect of formulation of intramuscular injections of phenothiazines on duration of activity.", "content": "Trifluoperazine and pericyazine were formulated using both the hydrochloride and embonate salts, and some comparisons were made with the activity of fluphenazine salt and ester formulations. Simple solutions in polyethylene glycol, gelled aqueous solutions, nonaqueous suspensions, multiple emulsions, and microencapsulated preparations were formulated, and their duration of activity was tested in dogs. While the multiple emulsion system showed some promise, a nylon microcapsule system produced significant prolonged activity of the drug after deep intramuscular injection.", "contents": "Effect of formulation of intramuscular injections of phenothiazines on duration of activity. Trifluoperazine and pericyazine were formulated using both the hydrochloride and embonate salts, and some comparisons were made with the activity of fluphenazine salt and ester formulations. Simple solutions in polyethylene glycol, gelled aqueous solutions, nonaqueous suspensions, multiple emulsions, and microencapsulated preparations were formulated, and their duration of activity was tested in dogs. While the multiple emulsion system showed some promise, a nylon microcapsule system produced significant prolonged activity of the drug after deep intramuscular injection."}
{"id": "PMID:11336", "title": "Pulmonary absorption studies utilizing in situ rat lung model: designing dosage regimen for bronchial delivery of new drug entities.", "content": "The absorption of 7-methylsulfinylxanthone-2-carboxylic acid, 7-(methylthio)xanthone-2-carboxylic acid, and their sodium salts from the respiratory tract of anesthetized rats was studied after intratracheal administration of 0.1 ml of a solution or suspension containing the drug. At various times after administration, the lungs and trachea were removed and assayed radiochemically for unabsorbed drug. Sodium 7-(methylthio)xanthone-2-carboxylate from solution was absorbed approximately 20 times faster than sodium 7-methylsulfinylxanthone-2-carboxylate from a solution. The absorption from solutions was three to four times faster than the absorption from suspensions. For inhalation aerosol dosage  forms intended for prophylactic use, the drug entity with slower systemic absorption probably would be more desirable than the drug entity with rapid absorption. Rapid systemic absorption following inhalation of powder or liquid aerosols would lead to more frequent dosing if the biological activity is related to the drug concentration in the tracheobronchial tissues. Therefore, the powder or liquid inhalation aerosols of organic acids rather than the corresponding sodium salts may be preferable for designing a dosage regimen. However, if the dosage form is intended for utilizing the bronchodilator activity of the compound, the drug entity with rapid absorption is more desirable. Therefore, in the treatment of asthmatic attacks, liquid or powder inhalation aerosols of the sodium salt of the rapidly absorbing drug entity are preferable. The absorption rates were directly proportional to concentration when the initial concentration of sodium 7-methylsulfinylxanthone-2-carboxylate was varied over a 333-fold range. The effect of the pH of the drug solution administered intratracheally to the rat lung indicated a sharp increase in the pulmonary absorption at a pH near the pKa. The results suggested that structurally related xanthones are absorbed possibly by passive diffusion across the lipoidal region of the pulmonary membranes and that the absorption of organic acids and organic electrolytes is mainly controlled by the lipid solubility of the unionized species.", "contents": "Pulmonary absorption studies utilizing in situ rat lung model: designing dosage regimen for bronchial delivery of new drug entities. The absorption of 7-methylsulfinylxanthone-2-carboxylic acid, 7-(methylthio)xanthone-2-carboxylic acid, and their sodium salts from the respiratory tract of anesthetized rats was studied after intratracheal administration of 0.1 ml of a solution or suspension containing the drug. At various times after administration, the lungs and trachea were removed and assayed radiochemically for unabsorbed drug. Sodium 7-(methylthio)xanthone-2-carboxylate from solution was absorbed approximately 20 times faster than sodium 7-methylsulfinylxanthone-2-carboxylate from a solution. The absorption from solutions was three to four times faster than the absorption from suspensions. For inhalation aerosol dosage  forms intended for prophylactic use, the drug entity with slower systemic absorption probably would be more desirable than the drug entity with rapid absorption. Rapid systemic absorption following inhalation of powder or liquid aerosols would lead to more frequent dosing if the biological activity is related to the drug concentration in the tracheobronchial tissues. Therefore, the powder or liquid inhalation aerosols of organic acids rather than the corresponding sodium salts may be preferable for designing a dosage regimen. However, if the dosage form is intended for utilizing the bronchodilator activity of the compound, the drug entity with rapid absorption is more desirable. Therefore, in the treatment of asthmatic attacks, liquid or powder inhalation aerosols of the sodium salt of the rapidly absorbing drug entity are preferable. The absorption rates were directly proportional to concentration when the initial concentration of sodium 7-methylsulfinylxanthone-2-carboxylate was varied over a 333-fold range. The effect of the pH of the drug solution administered intratracheally to the rat lung indicated a sharp increase in the pulmonary absorption at a pH near the pKa. The results suggested that structurally related xanthones are absorbed possibly by passive diffusion across the lipoidal region of the pulmonary membranes and that the absorption of organic acids and organic electrolytes is mainly controlled by the lipid solubility of the unionized species."}
{"id": "PMID:11337", "title": "Colorimetric assay for guaiacol O-methyltransferase.", "content": "A relatively simple colorimetric assay was developed for guaiacol O-methyltransferase. Monomethylated phenolic acid substrates are enzymatically methylated to their corresponding dimethoxyl compounds; S-adenosylmethionine serves as the methyl donor. Enzymatic activity is measured by colorimetric assay of the monomethylated (nonreacted) substrate by coupling of the phenolic acid with a diazotized sulfanilic acid. The methoxyl and hydroxyl groups may be in the 3,4- or 4,3-positions on the substrate molecules; however, a side chain (COOH) or a substituted side chain is necessary for enzyme action. The radioactive demonstration of guaiacol O-methyltransferase as a separate entity from catechol O-methyl-transferase was confirmed.", "contents": "Colorimetric assay for guaiacol O-methyltransferase. A relatively simple colorimetric assay was developed for guaiacol O-methyltransferase. Monomethylated phenolic acid substrates are enzymatically methylated to their corresponding dimethoxyl compounds; S-adenosylmethionine serves as the methyl donor. Enzymatic activity is measured by colorimetric assay of the monomethylated (nonreacted) substrate by coupling of the phenolic acid with a diazotized sulfanilic acid. The methoxyl and hydroxyl groups may be in the 3,4- or 4,3-positions on the substrate molecules; however, a side chain (COOH) or a substituted side chain is necessary for enzyme action. The radioactive demonstration of guaiacol O-methyltransferase as a separate entity from catechol O-methyl-transferase was confirmed."}
{"id": "PMID:11338", "title": "Investigations on metabolic modulation of p-aminohippurate accumulation by rabbit renal cortical slices.", "content": "Preparation and incubation of renal cortical slices from adult, female, New Zealand white rabbit depleted tissue citrate concentration. Acetate (10.0 mM) in the incubation significantly increased slice citrate concentration and p-aminohippurate (PAH) accumulation. Physiological concentrations of citrate increased PAH accumulation and final medium pH. increasing concentrations of citrate produced a biphasic effect on PAH accumulation. These data suggested that citrate may act as an intracellular modulator of organic anion transport. This hypothesis was tested with other stimulators of PAH accumulation. Physiological concentrations of alpha-ketoglutarate or succinate increased slice accumulation of PAH. Higher concentrations of either substrate significantly inhibited PAH accumulation. Final medium pH increased with increased medium concentration of both substrates. alpha-Ketoglutarate (0.5 mM) increased PAH accumulation but had no effect on slice citrate concentration. Glucose did not alter either PAH accumulation or slice citrate concentration. Slices incubated without substrate were depleted of citrate but not of alpha-ketoglutarate. Acetate (1.0 mM) significantly increased slice concentration of both alpha-ketoglutarate and citrate. These data suggested that organic anion transport could be modulated by several metabolic intermediates acting through similar but separate mechanisms.", "contents": "Investigations on metabolic modulation of p-aminohippurate accumulation by rabbit renal cortical slices. Preparation and incubation of renal cortical slices from adult, female, New Zealand white rabbit depleted tissue citrate concentration. Acetate (10.0 mM) in the incubation significantly increased slice citrate concentration and p-aminohippurate (PAH) accumulation. Physiological concentrations of citrate increased PAH accumulation and final medium pH. increasing concentrations of citrate produced a biphasic effect on PAH accumulation. These data suggested that citrate may act as an intracellular modulator of organic anion transport. This hypothesis was tested with other stimulators of PAH accumulation. Physiological concentrations of alpha-ketoglutarate or succinate increased slice accumulation of PAH. Higher concentrations of either substrate significantly inhibited PAH accumulation. Final medium pH increased with increased medium concentration of both substrates. alpha-Ketoglutarate (0.5 mM) increased PAH accumulation but had no effect on slice citrate concentration. Glucose did not alter either PAH accumulation or slice citrate concentration. Slices incubated without substrate were depleted of citrate but not of alpha-ketoglutarate. Acetate (1.0 mM) significantly increased slice concentration of both alpha-ketoglutarate and citrate. These data suggested that organic anion transport could be modulated by several metabolic intermediates acting through similar but separate mechanisms."}
{"id": "PMID:11339", "title": "Properties of the larval neuromuscular junction in Drosophila melanogaster.", "content": "The anatomy and physiology of the Drosophila larval neuromuscular junction were studied. 2. The dependence of muscle resting potentials on [K+]o and [Na+]o follows the Goldman-Hodgkin-Katz equation (PNa/PK=0-23). Chloride ions distribute passively across the membrane. 3. The mean specific membrane resistance of muscle fibres is 4-3 X 10(3) omega cm2, and the mean specific membrane capacitance is 7-1 muF/cm2. The muscle fibre is virtually isopotential. 4. Transmitter release is quantal. Both the miniature excitatory junctional potential and the evoked release follow the Poisson distribution. 5. Transmitter release depends on approximately the fourth power of [Ca2+]o. If Sr2+ replaces Ca2+, it depends on approximately the fourth power of [Sr2+]o. Mg2+ reduces transmitter release without altering the fourth power dependence on [Ca2+]o.", "contents": "Properties of the larval neuromuscular junction in Drosophila melanogaster. The anatomy and physiology of the Drosophila larval neuromuscular junction were studied. 2. The dependence of muscle resting potentials on [K+]o and [Na+]o follows the Goldman-Hodgkin-Katz equation (PNa/PK=0-23). Chloride ions distribute passively across the membrane. 3. The mean specific membrane resistance of muscle fibres is 4-3 X 10(3) omega cm2, and the mean specific membrane capacitance is 7-1 muF/cm2. The muscle fibre is virtually isopotential. 4. Transmitter release is quantal. Both the miniature excitatory junctional potential and the evoked release follow the Poisson distribution. 5. Transmitter release depends on approximately the fourth power of [Ca2+]o. If Sr2+ replaces Ca2+, it depends on approximately the fourth power of [Sr2+]o. Mg2+ reduces transmitter release without altering the fourth power dependence on [Ca2+]o."}
{"id": "PMID:11340", "title": "The effects of pH changes on the frequency of miniature end-plate potentials at the frog neuromuscular junction.", "content": "As reported by Landau & Nachshen (1975), a decrease in extracellular pH at the frog neuromuscular junction leads to an increase in min.e.p.p. frequency. 2. Decreasing the extracellular pH still increases the min.e.p.p. frequency when the bathing Ringer contains 10 mM-Ca2+, in place of the usual 2-5 mM. At the mammalian neuromuscular junction, the elevated Ca2+ blocks the effect of the pH change on the min.e.p.p. frequency (Hubbard, Jones & Landau, 1968). 3. In Cl--free solution (isethionate or methylsulphate substitution) min.e.p.p. frequency is no longer a monotonic function of decreasing pH. Instead there is an optimum pH for spontaneous release between pH 6-6 and 8-6. 4. This suggests that in Cl- containing Ringer min.e.p.p. frequency increases with increasing extracellular acidity because there is a change in the PCl of the nerve terminal leading to a depolarization. In agreement with this idea,in low Ca2+ Ringer, acid pH has little effect on the min.e.p.p. frequency. 5. Decreasing the intracellular pH by raising PCO2 produces substantial increases in the min.e.p.p. frequency. The effects are much greater than the effects of equal changes of H+ in the extracellular solution. 6. Possible explanations for the effects of increased PCO2 are discussed. Although release of Ca2+ from mitochondria or other unknown effects of intracellular pH change or molecular CO2 are possible, the results do give some support to the hypothesis that an important step in transmitter release involves an electrostatic repulsion between fixed membrane surface charges on the transmitter containing vesicles and the inner face of the nerve terminal. The surface charge density would be decreased by a lower pH in the axoplasm, and this would increase the rate of spontaneous transmitter release, in agreement with the observations.", "contents": "The effects of pH changes on the frequency of miniature end-plate potentials at the frog neuromuscular junction. As reported by Landau & Nachshen (1975), a decrease in extracellular pH at the frog neuromuscular junction leads to an increase in min.e.p.p. frequency. 2. Decreasing the extracellular pH still increases the min.e.p.p. frequency when the bathing Ringer contains 10 mM-Ca2+, in place of the usual 2-5 mM. At the mammalian neuromuscular junction, the elevated Ca2+ blocks the effect of the pH change on the min.e.p.p. frequency (Hubbard, Jones & Landau, 1968). 3. In Cl--free solution (isethionate or methylsulphate substitution) min.e.p.p. frequency is no longer a monotonic function of decreasing pH. Instead there is an optimum pH for spontaneous release between pH 6-6 and 8-6. 4. This suggests that in Cl- containing Ringer min.e.p.p. frequency increases with increasing extracellular acidity because there is a change in the PCl of the nerve terminal leading to a depolarization. In agreement with this idea,in low Ca2+ Ringer, acid pH has little effect on the min.e.p.p. frequency. 5. Decreasing the intracellular pH by raising PCO2 produces substantial increases in the min.e.p.p. frequency. The effects are much greater than the effects of equal changes of H+ in the extracellular solution. 6. Possible explanations for the effects of increased PCO2 are discussed. Although release of Ca2+ from mitochondria or other unknown effects of intracellular pH change or molecular CO2 are possible, the results do give some support to the hypothesis that an important step in transmitter release involves an electrostatic repulsion between fixed membrane surface charges on the transmitter containing vesicles and the inner face of the nerve terminal. The surface charge density would be decreased by a lower pH in the axoplasm, and this would increase the rate of spontaneous transmitter release, in agreement with the observations."}
{"id": "PMID:11341", "title": "The effect of local changes in potassium and bicarbonate concentration on hypothalamic blood flow in the rabbit.", "content": "Blood flow has been measured locally in the hypothalamus of anaesthetized rabbits by measuring the clearance of small volumes (5-20 mul.) of a mock cerebrospinal fluid solution containing 133Xe. The effect of varying the [K+] or [HCO-3] of the 133Xe-containing solution on local hypothalamic blood flow has been investigated. 2. There was an increase in local hypothalamic blood flow if the 133Xe-containing solution was HCO3--free; raising the [HCO--3,] of the solution to 40 mM caused a fall in local blood flow. 3. There was an increase in local hypothalamic blood flow when 133Xe was injectedin a mock cerebrospinal fluid containing 10 or 20 mM-[K+]. There was no significant change in  blood flow if a K+-free or a 40 mM [K+] solution was used. 4. The decrease in hypothalamic blood flow caused by injecting a 40 mM-[HCO3] solution could be reversed by the addition of 20 mM [K+] to the solution. There was no further increase in blood flow if 20 mM-[K+] was added to a HCO3--free solution. 5. It is concluded that local blood flow in the hypothalamus changes as a result of variation in local [K+] as well as local [HCO-3]. The changes in blood flow in the brain which accompany neuronal activity could be mediated by variation in local [K+].", "contents": "The effect of local changes in potassium and bicarbonate concentration on hypothalamic blood flow in the rabbit. Blood flow has been measured locally in the hypothalamus of anaesthetized rabbits by measuring the clearance of small volumes (5-20 mul.) of a mock cerebrospinal fluid solution containing 133Xe. The effect of varying the [K+] or [HCO-3] of the 133Xe-containing solution on local hypothalamic blood flow has been investigated. 2. There was an increase in local hypothalamic blood flow if the 133Xe-containing solution was HCO3--free; raising the [HCO--3,] of the solution to 40 mM caused a fall in local blood flow. 3. There was an increase in local hypothalamic blood flow when 133Xe was injectedin a mock cerebrospinal fluid containing 10 or 20 mM-[K+]. There was no significant change in  blood flow if a K+-free or a 40 mM [K+] solution was used. 4. The decrease in hypothalamic blood flow caused by injecting a 40 mM-[HCO3] solution could be reversed by the addition of 20 mM [K+] to the solution. There was no further increase in blood flow if 20 mM-[K+] was added to a HCO3--free solution. 5. It is concluded that local blood flow in the hypothalamus changes as a result of variation in local [K+] as well as local [HCO-3]. The changes in blood flow in the brain which accompany neuronal activity could be mediated by variation in local [K+]."}
{"id": "PMID:11342", "title": "On the receptors which mediate the hyperpolarization of salivary gland cells of Nauphoeta cinerea Olivier.", "content": "The actions of sympathomimetics and of catecholamine antagonists have been investigated on the membrane potential and responses to nerve stimulation of acinar cells of the salivary gland of Nauphoeta cinerea Olivier. 2. Hyperpolarizations such as those evoked by nerve stimulation and by low concentrations of adrenaline, noradrenaline and dopamine were not produced by the alpha-agonists amidephrine and methoxamine. Isoprenaline was active, but only in concentrations above 100 muM. 3. Tyramine, an indirectly acting sympathomimetic, and high concentrations of methoxamine caused an increase in the rate of the small transient hyperpolarizations sometimes seen in the absence of stimulation. 4. The response to nerve stimulation was unaffected by propranolol (20 muM) an alpha-adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, reduced matching responses to nerve stimulation and to dopamine to about the same extent. 5. As on other systems responsive to low concentrations of dopamine, apomorphine was active, although only in high concentration, and ergometrine and methysergide were antagonistic both to nerve stimulation and to dopamine.", "contents": "On the receptors which mediate the hyperpolarization of salivary gland cells of Nauphoeta cinerea Olivier. The actions of sympathomimetics and of catecholamine antagonists have been investigated on the membrane potential and responses to nerve stimulation of acinar cells of the salivary gland of Nauphoeta cinerea Olivier. 2. Hyperpolarizations such as those evoked by nerve stimulation and by low concentrations of adrenaline, noradrenaline and dopamine were not produced by the alpha-agonists amidephrine and methoxamine. Isoprenaline was active, but only in concentrations above 100 muM. 3. Tyramine, an indirectly acting sympathomimetic, and high concentrations of methoxamine caused an increase in the rate of the small transient hyperpolarizations sometimes seen in the absence of stimulation. 4. The response to nerve stimulation was unaffected by propranolol (20 muM) an alpha-adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, reduced matching responses to nerve stimulation and to dopamine to about the same extent. 5. As on other systems responsive to low concentrations of dopamine, apomorphine was active, although only in high concentration, and ergometrine and methysergide were antagonistic both to nerve stimulation and to dopamine."}
{"id": "PMID:11343", "title": "Heat treatment of laser-welded gold alloys.", "content": "(1) Three alloys, G-3, SMG-2,  and Ceramco-0, showed no ductility in the aswelded condition. (2) The Ney G-3 as-welded samples had no ductility, but heat treating greatly increased their yield stress. (3) The simulated ceramic firing cycle created a small amount of ductility in SMG-2, but the lowering of the yield stress in Ceramco-0 renders the welds dangerously weak even with improved ductility. (4) The Jelenko F as-welded specimens were acceptable. Heat treatment improved the joints slightly, but this is not considered necessary. (5) The Ney B-2 as-welded specimens produced satisfactory joints which did not benefit from heat treatment. The large loss in ductility with heat treatment is considered undesirable. (6) The unpredictable behavior of Ceramco-0 in this study suggests the need to evaluate each alloy individually before clinical application.", "contents": "Heat treatment of laser-welded gold alloys. (1) Three alloys, G-3, SMG-2,  and Ceramco-0, showed no ductility in the aswelded condition. (2) The Ney G-3 as-welded samples had no ductility, but heat treating greatly increased their yield stress. (3) The simulated ceramic firing cycle created a small amount of ductility in SMG-2, but the lowering of the yield stress in Ceramco-0 renders the welds dangerously weak even with improved ductility. (4) The Jelenko F as-welded specimens were acceptable. Heat treatment improved the joints slightly, but this is not considered necessary. (5) The Ney B-2 as-welded specimens produced satisfactory joints which did not benefit from heat treatment. The large loss in ductility with heat treatment is considered undesirable. (6) The unpredictable behavior of Ceramco-0 in this study suggests the need to evaluate each alloy individually before clinical application."}
{"id": "PMID:11345", "title": "Correlation of opiate receptor affinity with analgetic effects of meperidine homologues.", "content": "The affinity for opiate receptor sites in brain tissue  in a series of N-substituted meperidine homologues has been compared with the analgetic potency of these compounds in mice. There is a good correlation between affinity for opiate receptor binding sites assayed in the presence of sodium and analgetic potency for homologues whose N-substituent has six or fewer carbons. The apparent discrepancy between the weak affinity of these drugs for opiate receptors and their fairly potent analgetic effects in vivo can be explained by meperidine's efficient penetration into brain.", "contents": "Correlation of opiate receptor affinity with analgetic effects of meperidine homologues. The affinity for opiate receptor sites in brain tissue  in a series of N-substituted meperidine homologues has been compared with the analgetic potency of these compounds in mice. There is a good correlation between affinity for opiate receptor binding sites assayed in the presence of sodium and analgetic potency for homologues whose N-substituent has six or fewer carbons. The apparent discrepancy between the weak affinity of these drugs for opiate receptors and their fairly potent analgetic effects in vivo can be explained by meperidine's efficient penetration into brain."}
{"id": "PMID:11346", "title": "Pharmacological activity of nitroxide analogues of dichloroisoproterenol and propranolol.", "content": "Spin-labeled analogues of dichloroisoproterenol and propranolol were synthesized. It was found that the KD's of both probes for the beta-adrenergic receptors of frog erythrocytes were about 30-fold higher than the KD's previously reported for the parent antagonists. Thus the introduction of a bulky nitroxide moiety in place of the isopropyl group on the amino nitrogen is associated with a decrease in affinity for the beta-adrenergic receptors. Nonetheless, the affinity of the spin-labeled propranolol would appear to be within a range compatible with EPR measurements.", "contents": "Pharmacological activity of nitroxide analogues of dichloroisoproterenol and propranolol. Spin-labeled analogues of dichloroisoproterenol and propranolol were synthesized. It was found that the KD's of both probes for the beta-adrenergic receptors of frog erythrocytes were about 30-fold higher than the KD's previously reported for the parent antagonists. Thus the introduction of a bulky nitroxide moiety in place of the isopropyl group on the amino nitrogen is associated with a decrease in affinity for the beta-adrenergic receptors. Nonetheless, the affinity of the spin-labeled propranolol would appear to be within a range compatible with EPR measurements."}
{"id": "PMID:11347", "title": "Cycloalkanones. 9. Comparison of analogues which inhibit cholesterol and fatty acid synthesis.", "content": "A number of 2,8-dibenzylcyclooctanone analogues inhibited the HMG-CoA reductases activity of Holtzman male rat liver, whereas only 2-octanone, 2-hexadecanone, 2,8-dibenzylcyclooctanone derivatives, and 2-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4-pyrone inhibited fatty acid synthetase activity. 2-Octanone significantly lowered serum cholesterol, triglycerides, and glycerol levels in Holtzman male rats and serlm cholesterol in male CF1 mice. Serum lipase activity was significantly elevated in rats administered 20 mg/kg/day of 2-octanone for 16 days. The activity of liver HMG-CoA reductase was inhibited in mice administered 10 mg/kg/day of 2-octanone for 10 days and in mouse and rat liver in vitro by 10 mg of 2-octanone. In mice, fecal excretion of [14C]cholesterol and tripalmitin was accelerated whereas palmitic acid and cholesteryl oleate were not affected by 10 mg/kg/day of 2-octanone. The LD50 in male mice for 2-octanone was 1.6g/kg.", "contents": "Cycloalkanones. 9. Comparison of analogues which inhibit cholesterol and fatty acid synthesis. A number of 2,8-dibenzylcyclooctanone analogues inhibited the HMG-CoA reductases activity of Holtzman male rat liver, whereas only 2-octanone, 2-hexadecanone, 2,8-dibenzylcyclooctanone derivatives, and 2-bis(4-chlorophenyl)-3,5-dimethyltetrahydro-4-pyrone inhibited fatty acid synthetase activity. 2-Octanone significantly lowered serum cholesterol, triglycerides, and glycerol levels in Holtzman male rats and serlm cholesterol in male CF1 mice. Serum lipase activity was significantly elevated in rats administered 20 mg/kg/day of 2-octanone for 16 days. The activity of liver HMG-CoA reductase was inhibited in mice administered 10 mg/kg/day of 2-octanone for 10 days and in mouse and rat liver in vitro by 10 mg of 2-octanone. In mice, fecal excretion of [14C]cholesterol and tripalmitin was accelerated whereas palmitic acid and cholesteryl oleate were not affected by 10 mg/kg/day of 2-octanone. The LD50 in male mice for 2-octanone was 1.6g/kg."}
{"id": "PMID:11348", "title": "Structural characteristics of the saxitoxin receptor on nerve.", "content": "The effects of uranyl ion (UO22+; at low concentrations binds specifically to phosphate groups) and the cationic dye methylene blue (MB+; binds strongly to carboxyl groups) on saxitoxin (STX) potency in crayfish axon has been studied by means of intracellular microelectrodes. At pH 6.00 +/- 0.05 and 13.5 mM Ca2+, addition of 10.0 muM UO22+ + 5.0 nM STX had only slightly, if any, less effect on the spike's maximum rate of rise [0.79 +/- 0.04 (viz., mean +/- SEM) of control value] than did addition of 5.0 nM STX alone (0.72 +/- 0.05). Under the same conditions of pH and Ca2+ concentration, 1.0 mM MB+ had approximately the same effect: 1.0 mM MB+ + 5.0 nM STX, 0.76 +/- 0.03; 5.0 nM STX alone, 0.70 +/- 0.04. However, at pH 7.00 +/- 0.05 and lower Ca2+ concentrations, 1.0 mM MB+ significantly reduced STX potency. Using 6.0 mM Ca2+: 1.0 mM MB+ + 5.0 nM STX, 0.92 +/- 0.01; 5.0 nM STX alone, 0.68 +/- 0.08. Using 3.0 mM Ca2+, the corresponding values were 0.94 +/- 0.03 and 0.67 +/- 0.04. It is concluded that: (1) In accord with previous suggestions, the ionized acidic group known to exist in the Na channel (and to which a guanidinium group of STX appears to bind) is very likely a carboxyl group and not a phosphate group. (2) The accessible part of the Na channel mouth serving as the saxitoxin receptor probably does not include phospholipid in its structure proper.", "contents": "Structural characteristics of the saxitoxin receptor on nerve. The effects of uranyl ion (UO22+; at low concentrations binds specifically to phosphate groups) and the cationic dye methylene blue (MB+; binds strongly to carboxyl groups) on saxitoxin (STX) potency in crayfish axon has been studied by means of intracellular microelectrodes. At pH 6.00 +/- 0.05 and 13.5 mM Ca2+, addition of 10.0 muM UO22+ + 5.0 nM STX had only slightly, if any, less effect on the spike's maximum rate of rise [0.79 +/- 0.04 (viz., mean +/- SEM) of control value] than did addition of 5.0 nM STX alone (0.72 +/- 0.05). Under the same conditions of pH and Ca2+ concentration, 1.0 mM MB+ had approximately the same effect: 1.0 mM MB+ + 5.0 nM STX, 0.76 +/- 0.03; 5.0 nM STX alone, 0.70 +/- 0.04. However, at pH 7.00 +/- 0.05 and lower Ca2+ concentrations, 1.0 mM MB+ significantly reduced STX potency. Using 6.0 mM Ca2+: 1.0 mM MB+ + 5.0 nM STX, 0.92 +/- 0.01; 5.0 nM STX alone, 0.68 +/- 0.08. Using 3.0 mM Ca2+, the corresponding values were 0.94 +/- 0.03 and 0.67 +/- 0.04. It is concluded that: (1) In accord with previous suggestions, the ionized acidic group known to exist in the Na channel (and to which a guanidinium group of STX appears to bind) is very likely a carboxyl group and not a phosphate group. (2) The accessible part of the Na channel mouth serving as the saxitoxin receptor probably does not include phospholipid in its structure proper."}
{"id": "PMID:11349", "title": "Ca binding to the human red cell membrane: characterization of membrane preparations and binding sites.", "content": "Inside out and right side out vesicles were used to study the sidedness of Ca binding to the human red cell membrane. It was shown that these vesicles exhibited only a limited permeability to Ca, enabling the independent characterization of Ca binding to the extracellular and cytoplasmic membrane surfaces...", "contents": "Ca binding to the human red cell membrane: characterization of membrane preparations and binding sites. Inside out and right side out vesicles were used to study the sidedness of Ca binding to the human red cell membrane. It was shown that these vesicles exhibited only a limited permeability to Ca, enabling the independent characterization of Ca binding to the extracellular and cytoplasmic membrane surfaces..."}
{"id": "PMID:11350", "title": "Influence of extracellular pH on the viability and morphology of tumor cells exposed to hyperthermia.", "content": "The influence of hyperthermia (42.5 degrees C) on the viability and morphology of L1A2 ascites cells incubated at various pH levels (6.4-7.2) was studied. In contrast to unheated cells, increased extracellular acidity in hyperthermically treated tumor cells was associated with markedly reduced viability of the tumor cells exposed to hyperthermia. The cells heated at neutral pH underwent ultrastructural nuclear changes; the most prominent were the appearance of filamentous bundles and increased perichromatin granules. The cells heated under more acid conditions had an increased lysosomal activity and intense cell lysis resulting in lethal damage to the entire cell population within 6 hours after treatment. The active mechanism was not clear, but cell membrane lesions combined with the increased lysosome activity seemed of major importance in the mechanism of heat-induced damage to tumor cells kept in an acid milieu.", "contents": "Influence of extracellular pH on the viability and morphology of tumor cells exposed to hyperthermia. The influence of hyperthermia (42.5 degrees C) on the viability and morphology of L1A2 ascites cells incubated at various pH levels (6.4-7.2) was studied. In contrast to unheated cells, increased extracellular acidity in hyperthermically treated tumor cells was associated with markedly reduced viability of the tumor cells exposed to hyperthermia. The cells heated at neutral pH underwent ultrastructural nuclear changes; the most prominent were the appearance of filamentous bundles and increased perichromatin granules. The cells heated under more acid conditions had an increased lysosomal activity and intense cell lysis resulting in lethal damage to the entire cell population within 6 hours after treatment. The active mechanism was not clear, but cell membrane lesions combined with the increased lysosome activity seemed of major importance in the mechanism of heat-induced damage to tumor cells kept in an acid milieu."}
{"id": "PMID:11351", "title": "Estrogen-induced Leydig cell tumor in the mouse: a model system for the study of carcinogenesis and hormone dependency.", "content": "Malignant neoplasms of endocrine tissues represent almost half of the cancers diagnosed clinically in the United States, and many of these respond to hormonal therapies. Estrogen-induced testicular Leydig cell tumors in the mouse would seem to represent a realistic model for the laboratory investigation of this significant group of cancers. Data accumulated over the past few years clearly show that the Leydig cell is a target tissue for estrogens. Administering large doses of estrogen results in a reduction of enzymes converting progesterone to testosterone and induces a transient, but quantitatively very significant, synthesis of DNA in the Leydig cells of tumor-susceptible strains of mice. Neither of these actions of estrogen is mediated via the hypophysis. It has been demonstrated that the Leydig cells have specific protein receptors in their cytoplasm that bind estrogens and transport them to the nucleus where they are also bound. The genetic composition of the Leydig cells themselves is extremely important for the development of tumors. An adequately functioning pituitary gland is also essential for tumor formation. Confining the testes to the abdomen results in enzyme changes similar to those produced by estrogen administration and significantly augments the development of Leydig cell tumors. Once tumors form they frequently are dependent for their continued growth on estrogenic stimulation and/or on a functioning hypothysis. Regressed tumors may remain dormant for many months only to resume progressive growth when placed in and adequate hormone environment.", "contents": "Estrogen-induced Leydig cell tumor in the mouse: a model system for the study of carcinogenesis and hormone dependency. Malignant neoplasms of endocrine tissues represent almost half of the cancers diagnosed clinically in the United States, and many of these respond to hormonal therapies. Estrogen-induced testicular Leydig cell tumors in the mouse would seem to represent a realistic model for the laboratory investigation of this significant group of cancers. Data accumulated over the past few years clearly show that the Leydig cell is a target tissue for estrogens. Administering large doses of estrogen results in a reduction of enzymes converting progesterone to testosterone and induces a transient, but quantitatively very significant, synthesis of DNA in the Leydig cells of tumor-susceptible strains of mice. Neither of these actions of estrogen is mediated via the hypophysis. It has been demonstrated that the Leydig cells have specific protein receptors in their cytoplasm that bind estrogens and transport them to the nucleus where they are also bound. The genetic composition of the Leydig cells themselves is extremely important for the development of tumors. An adequately functioning pituitary gland is also essential for tumor formation. Confining the testes to the abdomen results in enzyme changes similar to those produced by estrogen administration and significantly augments the development of Leydig cell tumors. Once tumors form they frequently are dependent for their continued growth on estrogenic stimulation and/or on a functioning hypothysis. Regressed tumors may remain dormant for many months only to resume progressive growth when placed in and adequate hormone environment."}
{"id": "PMID:11352", "title": "Metabolism of diethylstilbestrol by rat liver: a preliminary report.", "content": "Aerobic incubation of a misture of E[1,1,1-D3]-3,4;bis(p-hydroxyphenyl)-hex-3-ene admixed with an approximately equimolar amount of unlabeled diethylstilbestrol and [ 2-(14)C ] diethylstilbestrol with rat liver homogenates in the presence of NADPH yielded water-soluble metabolites as well as products more and less polar than the starting material. Addition of 5-adenosyl-L-methionine increased the quantity of nonpolar metabolites. Incubation with rat liver microsomes yielded similar results. When polar metabolites from incubation with rat liver microsomes were incubated with catechol O-methyltransferase and S-adenosyl[methyl-3 H]-L-methionine there was conversion to 3H-labeled nonpolar products. Examination of reaction products by means of gas chronatography-mass spectrometry gave evidence for the formation of a dihydroxydiethylstilbestrol, a dihydroxydienestrol, and a monomethoxydiethylstilbestrol.", "contents": "Metabolism of diethylstilbestrol by rat liver: a preliminary report. Aerobic incubation of a misture of E[1,1,1-D3]-3,4;bis(p-hydroxyphenyl)-hex-3-ene admixed with an approximately equimolar amount of unlabeled diethylstilbestrol and [ 2-(14)C ] diethylstilbestrol with rat liver homogenates in the presence of NADPH yielded water-soluble metabolites as well as products more and less polar than the starting material. Addition of 5-adenosyl-L-methionine increased the quantity of nonpolar metabolites. Incubation with rat liver microsomes yielded similar results. When polar metabolites from incubation with rat liver microsomes were incubated with catechol O-methyltransferase and S-adenosyl[methyl-3 H]-L-methionine there was conversion to 3H-labeled nonpolar products. Examination of reaction products by means of gas chronatography-mass spectrometry gave evidence for the formation of a dihydroxydiethylstilbestrol, a dihydroxydienestrol, and a monomethoxydiethylstilbestrol."}
{"id": "PMID:11353", "title": "Reflections on Second Annual NCTR Hormone Research Symposium.", "content": "Hormones have widely different effects depending on species, dosage use, timing of dosage, route of administration, status of animals (re: pregnancy, stage of estrous cycle, age), and end point being measured. Hormones are essential to both maintenance and quality of life, and they occur in our environment with regularity. Hormones are seen by some persons as a regulatory dilemma because, when characterized under conditions of marked overdosage, the biological consequences are often undesirable. Because many of the naturally occurring hormones were identified long ago and have been studied for many decades, the reality is that much more knowledge is available on hormones than on more recently discovered substances, either naturally occurring or synthetic. The effects of hormones on tumors, either increases or decreases in incidence, appear to be indirect through alterations of normal physiological processes. The mechanism of action of hormones at the cellular level suggests that hormones are not involved in cancer by causing DNA changes, but in the degree of expression of changes in DNA that have occurred by other means. Key studies, especially at the molecular level, to further define the involvement of hormones in carcinogenesis should help us to define tolerance levels and aid with the regulatory dilemma.", "contents": "Reflections on Second Annual NCTR Hormone Research Symposium. Hormones have widely different effects depending on species, dosage use, timing of dosage, route of administration, status of animals (re: pregnancy, stage of estrous cycle, age), and end point being measured. Hormones are essential to both maintenance and quality of life, and they occur in our environment with regularity. Hormones are seen by some persons as a regulatory dilemma because, when characterized under conditions of marked overdosage, the biological consequences are often undesirable. Because many of the naturally occurring hormones were identified long ago and have been studied for many decades, the reality is that much more knowledge is available on hormones than on more recently discovered substances, either naturally occurring or synthetic. The effects of hormones on tumors, either increases or decreases in incidence, appear to be indirect through alterations of normal physiological processes. The mechanism of action of hormones at the cellular level suggests that hormones are not involved in cancer by causing DNA changes, but in the degree of expression of changes in DNA that have occurred by other means. Key studies, especially at the molecular level, to further define the involvement of hormones in carcinogenesis should help us to define tolerance levels and aid with the regulatory dilemma."}
{"id": "PMID:11354", "title": "Bromodeoxyuridine resistance induced in mouse lymphoma cells by microsomal activation of dimethylnitrosamine.", "content": "Many chemicals are not mutagenic per se, but when metabolized by mammalian tissues yield mutagenic products. Dimethylnitrosamine (DMN) is such a promutagen. It has no effect on cell growth or mutant frequency when incubated alone with L5178Y mouse lymphoma cells, but exerts both mutagenic and toxic effects when incubated in a microsome reaction mixture. Microsomes were prepared from C3H/f We 16-wk-old male mice by the calcium preciptation technique. L5178Y continuously cultured mouse lymphoma cells heterozygous for thymidine kinase (TK+/-) were incubated for 15 min with calcium-precipitated microsomes and various concentrations of DMN in appropriate reaction mixtures. After a 48-hr expression time, treated cells were cloned in soft agar with and without bromodeoxyuridine (BUdR) (50 mug/ml); 10 days later colonies grown to greater than about 200 mum diameter were counted. The frequency of BUdR-resistant (mutant) colonies increased linearly with the DMN concentration. A reconstruction experiment showed that the assay conditions did not significantly alter the relationship between parent and BUdR-resistant cells in growth and cloning efficiency. The smallest dose of DMN used in these experiments was 100mumol/liter, the one-sided (100 mumol greater than control frequency) -p value is 0.036. The locus is extremely sensitive to mutagenesis by DMN compared with other known mutagens at similar levels of cell survival.", "contents": "Bromodeoxyuridine resistance induced in mouse lymphoma cells by microsomal activation of dimethylnitrosamine. Many chemicals are not mutagenic per se, but when metabolized by mammalian tissues yield mutagenic products. Dimethylnitrosamine (DMN) is such a promutagen. It has no effect on cell growth or mutant frequency when incubated alone with L5178Y mouse lymphoma cells, but exerts both mutagenic and toxic effects when incubated in a microsome reaction mixture. Microsomes were prepared from C3H/f We 16-wk-old male mice by the calcium preciptation technique. L5178Y continuously cultured mouse lymphoma cells heterozygous for thymidine kinase (TK+/-) were incubated for 15 min with calcium-precipitated microsomes and various concentrations of DMN in appropriate reaction mixtures. After a 48-hr expression time, treated cells were cloned in soft agar with and without bromodeoxyuridine (BUdR) (50 mug/ml); 10 days later colonies grown to greater than about 200 mum diameter were counted. The frequency of BUdR-resistant (mutant) colonies increased linearly with the DMN concentration. A reconstruction experiment showed that the assay conditions did not significantly alter the relationship between parent and BUdR-resistant cells in growth and cloning efficiency. The smallest dose of DMN used in these experiments was 100mumol/liter, the one-sided (100 mumol greater than control frequency) -p value is 0.036. The locus is extremely sensitive to mutagenesis by DMN compared with other known mutagens at similar levels of cell survival."}
{"id": "PMID:11355", "title": "Absorption, utilization, and safety of aspartic acid.", "content": "The dicarboxylic amino acids, asparate and glutamate, occupy unique positions in intermediary metabolism, particularly in the mitochondria, where they play important roles in nitrogen and energy metabolism. Administration of large quantities of glutamate and asparate to the newborn mouse produces a variety of neurotoxic effects, the most marked of which is neuronal necrosis. Neurotoxic effects of glutamate and aspartate in animal species other than the rodent are highly controversial. In the most critical animal species, the infant subhuman primate, at least four research groups have failed to duplicate the original report of glutamate-induced neuronal necrosis. Marked elevations in plasma glutamate or aspartate must occur for development of neuronal necrosis. In the highly sensitive neonatal mouse, plasma glutamate plus plasma aspartate levels must reach 60-80 mumol/dl to produce even minimal neuronal necrosis. In the healthy neonatal primate, loads producing plasma glutamate levels ranging from 50 to 1,600 mumol/dl failed to produce neuronal necrosis in our studies. Thus, it is clear that (1) marked elevations in plasma glutamate and aspartate must occur for neuronal necrosis, and (2) threshold levels required to produce neuronal necrosis vary greatly with species. The available data indicate little danger to the healthy primate and humans from ingestion of the dicarboxylic amino acids under anything resembling a reasonable intake. However, there is no doubt that these amino acids are toxic to the neonatal mouse at high dose levels.", "contents": "Absorption, utilization, and safety of aspartic acid. The dicarboxylic amino acids, asparate and glutamate, occupy unique positions in intermediary metabolism, particularly in the mitochondria, where they play important roles in nitrogen and energy metabolism. Administration of large quantities of glutamate and asparate to the newborn mouse produces a variety of neurotoxic effects, the most marked of which is neuronal necrosis. Neurotoxic effects of glutamate and aspartate in animal species other than the rodent are highly controversial. In the most critical animal species, the infant subhuman primate, at least four research groups have failed to duplicate the original report of glutamate-induced neuronal necrosis. Marked elevations in plasma glutamate or aspartate must occur for development of neuronal necrosis. In the highly sensitive neonatal mouse, plasma glutamate plus plasma aspartate levels must reach 60-80 mumol/dl to produce even minimal neuronal necrosis. In the healthy neonatal primate, loads producing plasma glutamate levels ranging from 50 to 1,600 mumol/dl failed to produce neuronal necrosis in our studies. Thus, it is clear that (1) marked elevations in plasma glutamate and aspartate must occur for neuronal necrosis, and (2) threshold levels required to produce neuronal necrosis vary greatly with species. The available data indicate little danger to the healthy primate and humans from ingestion of the dicarboxylic amino acids under anything resembling a reasonable intake. However, there is no doubt that these amino acids are toxic to the neonatal mouse at high dose levels."}
{"id": "PMID:11356", "title": "Medex and their physician preceptors. Quality of care.", "content": "Studies of selected indicators of the process of care provided by a Medex and by a physician preceptor in seven rural practices suggest that the Medex is more likely to use appropriate laboratory tests and less likely to use inappropriate treatments. When outcomes of care were determined in 13 practices with a Medex and a preceptor, the patients seen by the Medex tended to fare about as well as those seen by a physician (71% versus 74%, respectively) in regaining their usual functional status. The addition of a Medex to a rural practice may thus produce both direct and indirected benefits.", "contents": "Medex and their physician preceptors. Quality of care. Studies of selected indicators of the process of care provided by a Medex and by a physician preceptor in seven rural practices suggest that the Medex is more likely to use appropriate laboratory tests and less likely to use inappropriate treatments. When outcomes of care were determined in 13 practices with a Medex and a preceptor, the patients seen by the Medex tended to fare about as well as those seen by a physician (71% versus 74%, respectively) in regaining their usual functional status. The addition of a Medex to a rural practice may thus produce both direct and indirected benefits."}
{"id": "PMID:11358", "title": "Benzodiazepines and withdrawal psychosis. Report of three cases.", "content": "Three cases of acute psychotic illness following sudden withdrawal from high daily doses of benzodiazepines were associated with agitation and confusion. Disorientation was prominent in two of the patients. None of the patients had had previous psychotic episodes. The condition of all patients was reversed dramatically with hypnotic drugs. Gradual withdrawal was successfully accomplished without relapse, with a follow-up of as much as one year. To our knowledge, this is the first such series in the literature.", "contents": "Benzodiazepines and withdrawal psychosis. Report of three cases. Three cases of acute psychotic illness following sudden withdrawal from high daily doses of benzodiazepines were associated with agitation and confusion. Disorientation was prominent in two of the patients. None of the patients had had previous psychotic episodes. The condition of all patients was reversed dramatically with hypnotic drugs. Gradual withdrawal was successfully accomplished without relapse, with a follow-up of as much as one year. To our knowledge, this is the first such series in the literature."}
{"id": "PMID:11359", "title": "Calcium uptake, release and Mg-ATPase activity of sarcoplasmic reticulum from arterial smooth muscle.", "content": "Sarcoplasmic reticulum (SR) isolated from rat aorta exhibited ATP dependent Ca2+ uptake in the presence of Mg2+. The maximum capacity and apparent binding constant were 23n moles/mg and 1.8 X 10(4) M (-1), respectively. The energy source of this active Ca2+ accumulation would be Mg-ATPase associated with the membrane. Ca2+ which was taken up inside of sarcoplasmic reticulum was released rapidly by washout with the medium containing no Ca2+. These facts suggest that sarcoplasmic reticulum in vascular smooth muscle cell may play and important role in the regulation of intracellular Ca2+ concentration.", "contents": "Calcium uptake, release and Mg-ATPase activity of sarcoplasmic reticulum from arterial smooth muscle. Sarcoplasmic reticulum (SR) isolated from rat aorta exhibited ATP dependent Ca2+ uptake in the presence of Mg2+. The maximum capacity and apparent binding constant were 23n moles/mg and 1.8 X 10(4) M (-1), respectively. The energy source of this active Ca2+ accumulation would be Mg-ATPase associated with the membrane. Ca2+ which was taken up inside of sarcoplasmic reticulum was released rapidly by washout with the medium containing no Ca2+. These facts suggest that sarcoplasmic reticulum in vascular smooth muscle cell may play and important role in the regulation of intracellular Ca2+ concentration."}
{"id": "PMID:11362", "title": "Influence of transepithelial potential difference on acidification in the toad urinary bladder.", "content": "The rate of urinary acidification by toad urinary bladders was measured in vitro by following the pH changes of the HCO3-/CO2-buffered Ringer's solutions bathing the mucosal and serosal sides of the bladder. Within the tolerated range of transepithelial potential differences (PD) (-100 to +100 mv), the rate of acidification was found to be a linear function of the PD. The rate of acidification could be increased by a favorable PD whether the PD was the spontaneous transepithelial PD due to sodium transport or a PD imposed in the absence of sodium transport, as when choline was substituted for Na or when amiloride blocked sodium transport. Acetazolamide inhibited both active and PD-driven acidification. Acidification rate was the same in 2.4 mM HCO3- and 1% CO2 as in 12 mM HCO3- and 5% CO2; again, acidification was increased equally by a favorable PD. PD-driven acidification was found to be linearly correlated with acidification occurring at short-circuit conditions. These findings suggest that the rate of acidification can be accelerated by the transepithelial PD in the absence of sodium transport and that the PD-driven component of acidification utilizes a transcellular pathway.", "contents": "Influence of transepithelial potential difference on acidification in the toad urinary bladder. The rate of urinary acidification by toad urinary bladders was measured in vitro by following the pH changes of the HCO3-/CO2-buffered Ringer's solutions bathing the mucosal and serosal sides of the bladder. Within the tolerated range of transepithelial potential differences (PD) (-100 to +100 mv), the rate of acidification was found to be a linear function of the PD. The rate of acidification could be increased by a favorable PD whether the PD was the spontaneous transepithelial PD due to sodium transport or a PD imposed in the absence of sodium transport, as when choline was substituted for Na or when amiloride blocked sodium transport. Acetazolamide inhibited both active and PD-driven acidification. Acidification rate was the same in 2.4 mM HCO3- and 1% CO2 as in 12 mM HCO3- and 5% CO2; again, acidification was increased equally by a favorable PD. PD-driven acidification was found to be linearly correlated with acidification occurring at short-circuit conditions. These findings suggest that the rate of acidification can be accelerated by the transepithelial PD in the absence of sodium transport and that the PD-driven component of acidification utilizes a transcellular pathway."}
{"id": "PMID:11363", "title": "[Early neuro-ophthalmological symptoms of periarteritis nodosa. A case report (author's transl)].", "content": "A report is given on a 47-year-old woman with periarteritis nodosa. A unilateral retinopathy with disseminated cotton-wool-spots surrounded by retinal haemorrhages and edema was observed. Fluoresceinangiography showed a multifocal constriction of the retinal capillaries. This lesion of the retinal vessels can be distinguished from those caused by hypertension. An acute immunological reaction has been suggested as the pathogenesis. Some authors have described this retinal lesion in collagen diseases as a \"toxic\" retinopathy. We prefer the term acute immunological microangiopathy (AIM).", "contents": "[Early neuro-ophthalmological symptoms of periarteritis nodosa. A case report (author's transl)]. A report is given on a 47-year-old woman with periarteritis nodosa. A unilateral retinopathy with disseminated cotton-wool-spots surrounded by retinal haemorrhages and edema was observed. Fluoresceinangiography showed a multifocal constriction of the retinal capillaries. This lesion of the retinal vessels can be distinguished from those caused by hypertension. An acute immunological reaction has been suggested as the pathogenesis. Some authors have described this retinal lesion in collagen diseases as a \"toxic\" retinopathy. We prefer the term acute immunological microangiopathy (AIM)."}
{"id": "PMID:11368", "title": "Isolated cortical granules: a model system for studying membrane fusion and calcium-mediated exocytosis.", "content": "Cortical granules are secretory vesicles bound to the inner surface of the plasma membrane of sea urchin eggs. Intact granules can be isolated by shearing away the cytoplasm of eggs which have been bonded to a protamine-coated surface. When Ca2+ is added to preparations of isolated granules the granules fuse with each other and release their contents. It is believed that isolated cortical granules may be an excellent model system for the biochemical study of exocytosis.", "contents": "Isolated cortical granules: a model system for studying membrane fusion and calcium-mediated exocytosis. Cortical granules are secretory vesicles bound to the inner surface of the plasma membrane of sea urchin eggs. Intact granules can be isolated by shearing away the cytoplasm of eggs which have been bonded to a protamine-coated surface. When Ca2+ is added to preparations of isolated granules the granules fuse with each other and release their contents. It is believed that isolated cortical granules may be an excellent model system for the biochemical study of exocytosis."}
{"id": "PMID:11373", "title": "[Current status of treatment and new aspects of the problems of the undescended testicle (author's transl)].", "content": "Early treatment of the undescended testicle was first demanded by Fischer, Bramann and Ramstedt early this century. From the 2nd year of life the number of the spermatogonia decreases rapidly, the diameter of the tubuli decreases, and distension and collaginization of the interstice are revealed by electron microscopy. The descended testis is also injured in unilateral maldescensus. The damage to the undescended testicle seen in the microscopic structure is secondary. Early treatment always begins with choriogonadotropin and only if this is not successful is surgery performed. Treatment with hormones and surgery guarantee normal development of the testicle. The results of follow-up studies show that fertility is favorably influenced by very early treatment.", "contents": "[Current status of treatment and new aspects of the problems of the undescended testicle (author's transl)]. Early treatment of the undescended testicle was first demanded by Fischer, Bramann and Ramstedt early this century. From the 2nd year of life the number of the spermatogonia decreases rapidly, the diameter of the tubuli decreases, and distension and collaginization of the interstice are revealed by electron microscopy. The descended testis is also injured in unilateral maldescensus. The damage to the undescended testicle seen in the microscopic structure is secondary. Early treatment always begins with choriogonadotropin and only if this is not successful is surgery performed. Treatment with hormones and surgery guarantee normal development of the testicle. The results of follow-up studies show that fertility is favorably influenced by very early treatment."}
{"id": "PMID:11374", "title": "[Morphologic changes in cryptorchism (author's transl)].", "content": "Histologic changes caused by malposition occur in the undescended testicle after the second year of life. Histologic changes like those seen in the human are found in experimental cryptorchism in dogs. The same pathologic changes also occur in the unilaterally descended testicle. The results of preliminary experiments in dogs allow the statement that in unilateral cryptorchism the damage to the contralateral, descended, testicle is produced by an autoimmunologic mechanism.", "contents": "[Morphologic changes in cryptorchism (author's transl)]. Histologic changes caused by malposition occur in the undescended testicle after the second year of life. Histologic changes like those seen in the human are found in experimental cryptorchism in dogs. The same pathologic changes also occur in the unilaterally descended testicle. The results of preliminary experiments in dogs allow the statement that in unilateral cryptorchism the damage to the contralateral, descended, testicle is produced by an autoimmunologic mechanism."}
{"id": "PMID:11375", "title": "[Surgical technique in the management of undescenced testis (author's transl)].", "content": "In cases of retentio abdominalis or inguinalis and of ectopic testis, surgery is performed about the 2nd year of life. Essentials of the operating technique are: incision of the skin must not be parallel to the spermatic cord; testes and spermatic cord must be mobilized without trauma; ideally a biopsy of the testis should be taken; any pulling of the spermatic cord and torsion of it during fixation of the testis should be avoided. If initial tensionfree placement of the testis in the scrotum is impossible, the operation should be carried out in 2 sessions with an interval of 6-12 months. In 241 cases of children operated on from 1972-1975 with 308 total operations, the author observed 2 recurrences and 1 deep infection (scrotal abscess).", "contents": "[Surgical technique in the management of undescenced testis (author's transl)]. In cases of retentio abdominalis or inguinalis and of ectopic testis, surgery is performed about the 2nd year of life. Essentials of the operating technique are: incision of the skin must not be parallel to the spermatic cord; testes and spermatic cord must be mobilized without trauma; ideally a biopsy of the testis should be taken; any pulling of the spermatic cord and torsion of it during fixation of the testis should be avoided. If initial tensionfree placement of the testis in the scrotum is impossible, the operation should be carried out in 2 sessions with an interval of 6-12 months. In 241 cases of children operated on from 1972-1975 with 308 total operations, the author observed 2 recurrences and 1 deep infection (scrotal abscess)."}
{"id": "PMID:11388", "title": "Phospholipid synthesis in mammary tissue. Choline and ethanolamine kinases: kinetic evidence for two discrete active sites.", "content": "Choline and ethanolamine kinases are located in the high speed supernatant of lactating bovine mammary gland. Maximum activities of choline and ethanolamine kinases were observed at pH 9.2 and 8.0, respectively, with the rate of ethanolamine phosphorylation being 1/15 that of choline phosphorylation. Activation energies of 29 joules (Q10--1.5) and 31 joules (Q10 = 1.5) were calculated between 3.4 and 31.3 C for choline kinase and ethanolamine kinase, respectively. Above 31.3 C, the Arrhenius plot deviated from linearity for both enzymes, suggesting that denaturation was occurring. An apparent Km of 0.25 mM for choline was obtained for choline kinase activity. The apparent Km of ethanolamine kinase for ethanolamine was unusually high (17 mM), the activity was not linear with increasing protein concentration. Activity was tripled and the Km decreased to 2.5 mM when the enzyme preparation was washed with butanol: benzene mixture, suggesting the presence of an endogenous competitive inhibitor(s), with respect to ethanolamine. Choline kinase was not affected by the solvent wash. Substrate competition studies revealed that choline kinase was slightly inhibited competitively by ethanolamine (apparent Ki = 19-21 mM), whereas choline was a potent competitive inhibitor of ethanolamine kinase (apparent Ki = 0.33-0.50 mM). The results indicated that these two kinase activities were mediated by two distinct active sites, possibly on a single protein. The significance of choline in the regulation of phosphatidylethanolamine synthesis is discussed.", "contents": "Phospholipid synthesis in mammary tissue. Choline and ethanolamine kinases: kinetic evidence for two discrete active sites. Choline and ethanolamine kinases are located in the high speed supernatant of lactating bovine mammary gland. Maximum activities of choline and ethanolamine kinases were observed at pH 9.2 and 8.0, respectively, with the rate of ethanolamine phosphorylation being 1/15 that of choline phosphorylation. Activation energies of 29 joules (Q10--1.5) and 31 joules (Q10 = 1.5) were calculated between 3.4 and 31.3 C for choline kinase and ethanolamine kinase, respectively. Above 31.3 C, the Arrhenius plot deviated from linearity for both enzymes, suggesting that denaturation was occurring. An apparent Km of 0.25 mM for choline was obtained for choline kinase activity. The apparent Km of ethanolamine kinase for ethanolamine was unusually high (17 mM), the activity was not linear with increasing protein concentration. Activity was tripled and the Km decreased to 2.5 mM when the enzyme preparation was washed with butanol: benzene mixture, suggesting the presence of an endogenous competitive inhibitor(s), with respect to ethanolamine. Choline kinase was not affected by the solvent wash. Substrate competition studies revealed that choline kinase was slightly inhibited competitively by ethanolamine (apparent Ki = 19-21 mM), whereas choline was a potent competitive inhibitor of ethanolamine kinase (apparent Ki = 0.33-0.50 mM). The results indicated that these two kinase activities were mediated by two distinct active sites, possibly on a single protein. The significance of choline in the regulation of phosphatidylethanolamine synthesis is discussed."}
{"id": "PMID:11389", "title": "Effect of early postnatal dietary sterculate on the fatty acid composition of rat liver and brain lipids.", "content": "Pregnant rats were fed a high carbohydrate diet containing either 1% trilinolein or 1% trilinolein with 0.2% methyl sterculate from 18 day gestation to 21 day postpartum. The pups were weaned at 21 days and continued on the same diet for an additional 10 days. The microsomal stearyl CoA desaturase activities of the liver were effectively inhibited. Liver triglycerides showed increases in the saturated fatty acids concentrations at the expense of the corresponding monoenes. The concentration of cis 6-7 octadecenoic acid was elevated. In liver phospholipids, the concentration of stearic acid was increased without a corresponding decrease in the oleic acid content. A drastic decrease in the nervonic acid (24:1, n-9) concentration of liver sphingomyelin was observed. The lipids of the brain did not contain sterculic acid, and brain desaturase activity was unaffected. There was no significant change in the concentration of monoenoic acids from 16:1 to 22:1. However, nervonic acid was decreased by 32%. These results suggest that brain nervonic acid may be derived from a precursor other than oleic acid.", "contents": "Effect of early postnatal dietary sterculate on the fatty acid composition of rat liver and brain lipids. Pregnant rats were fed a high carbohydrate diet containing either 1% trilinolein or 1% trilinolein with 0.2% methyl sterculate from 18 day gestation to 21 day postpartum. The pups were weaned at 21 days and continued on the same diet for an additional 10 days. The microsomal stearyl CoA desaturase activities of the liver were effectively inhibited. Liver triglycerides showed increases in the saturated fatty acids concentrations at the expense of the corresponding monoenes. The concentration of cis 6-7 octadecenoic acid was elevated. In liver phospholipids, the concentration of stearic acid was increased without a corresponding decrease in the oleic acid content. A drastic decrease in the nervonic acid (24:1, n-9) concentration of liver sphingomyelin was observed. The lipids of the brain did not contain sterculic acid, and brain desaturase activity was unaffected. There was no significant change in the concentration of monoenoic acids from 16:1 to 22:1. However, nervonic acid was decreased by 32%. These results suggest that brain nervonic acid may be derived from a precursor other than oleic acid."}
{"id": "PMID:11390", "title": "Effect of dietary fats on ovine adipose tissue metabolism.", "content": "The effects of different dietary fats on ovine adipose tissue metabolism have been investigated. Six-month old sheep were fed for 6 weeks a control diet or diets supplemented with either tallow or a mixture of sunflower seed oil and soybean oil, treated to protect the fats from hydrolysis and hydrogenation in the rumen, or with maize oil. The rates of fatty acid, glyceride glycerol, and CO2 formation were measured in perirenal and subcutaneous adipose tissue slices by following the incorporation of either 14C from labeled acetate or glucose, or 3H from tritiated water into the appropriate product. Feeding protected tallow or maize oil but not protected sunflower seed oil plus soybean oil resulted in reduced rates of fatty acid biosynthesis in both perirenal and subcutaneous adipose tissue slices and CO2 formation in perirenal adipose tissue. Feeding the fat-supplemented diets had no effect on the rate of glyceride glycerol formation. The fat-supplemented diets also resulted in reduced activities of various enzymes, thought to be involved in lipogenesis, measured in 105,000 x g supernatant fractions from adipose tissue homogenates. The results suggested that ovine adipose tissue lipogenesis is sensitive to both the amount and the nature of dietary fat.", "contents": "Effect of dietary fats on ovine adipose tissue metabolism. The effects of different dietary fats on ovine adipose tissue metabolism have been investigated. Six-month old sheep were fed for 6 weeks a control diet or diets supplemented with either tallow or a mixture of sunflower seed oil and soybean oil, treated to protect the fats from hydrolysis and hydrogenation in the rumen, or with maize oil. The rates of fatty acid, glyceride glycerol, and CO2 formation were measured in perirenal and subcutaneous adipose tissue slices by following the incorporation of either 14C from labeled acetate or glucose, or 3H from tritiated water into the appropriate product. Feeding protected tallow or maize oil but not protected sunflower seed oil plus soybean oil resulted in reduced rates of fatty acid biosynthesis in both perirenal and subcutaneous adipose tissue slices and CO2 formation in perirenal adipose tissue. Feeding the fat-supplemented diets had no effect on the rate of glyceride glycerol formation. The fat-supplemented diets also resulted in reduced activities of various enzymes, thought to be involved in lipogenesis, measured in 105,000 x g supernatant fractions from adipose tissue homogenates. The results suggested that ovine adipose tissue lipogenesis is sensitive to both the amount and the nature of dietary fat."}
{"id": "PMID:11393", "title": "Effect of glucose and sucrose on the survival in batch culture of Streptococcus mutans C67-1 and a non-cariogenic mutant C67-25. Morphological studies.", "content": "This study comprised an ultrastructural examination of a cariogenic strain of Streptococcus mutans, C67-1, and a non-cariogenic mutant of that strain, C67-25. The aim of the work was to define more clearly the relationship between S. mutans and dental caries and, more specifically, to elicit ultrastructural evidence for the conclusion from a previous investigation that the greater survival of the parent strain in sucrose broth at uncontrolled pH was related partly to the production in this medium of abundant extracellular polysaccharide (EPS). The strains were grown as previously in 5% (w/v) glucose or sucrose broths, the pH being either allowed to fall or maintained above 6.0, and processed by the thiosemicarbazide technique for election microscopy. It was confirmed that EPS was most abundant in the sucrose broth culture of the parent strain at uncontrolled pH. While the presence of abundant EPS relates to the greater survival of the parent strain in sucrose broth at uncontrolled pH, this organism possesses at least one other mechanism of survival in acid media, possibly dependent on cell wall properties, in view of its greater cell wall thickness and increased survival in pH-uncontrolled glucose broth in the absence of detectable EPS production. It is postulated that intracellular and extracellular polysaccharide formation, cell wall thickening and reduced viability were indicators of unfavourable growth conditions in the test media. Cariogenic strains of S. mutans appear to be able to survive better under such conditions and hence the prevalence of this and other polysaccharide-producing organisms in stagnant sites in natural dental plaques.", "contents": "Effect of glucose and sucrose on the survival in batch culture of Streptococcus mutans C67-1 and a non-cariogenic mutant C67-25. Morphological studies. This study comprised an ultrastructural examination of a cariogenic strain of Streptococcus mutans, C67-1, and a non-cariogenic mutant of that strain, C67-25. The aim of the work was to define more clearly the relationship between S. mutans and dental caries and, more specifically, to elicit ultrastructural evidence for the conclusion from a previous investigation that the greater survival of the parent strain in sucrose broth at uncontrolled pH was related partly to the production in this medium of abundant extracellular polysaccharide (EPS). The strains were grown as previously in 5% (w/v) glucose or sucrose broths, the pH being either allowed to fall or maintained above 6.0, and processed by the thiosemicarbazide technique for election microscopy. It was confirmed that EPS was most abundant in the sucrose broth culture of the parent strain at uncontrolled pH. While the presence of abundant EPS relates to the greater survival of the parent strain in sucrose broth at uncontrolled pH, this organism possesses at least one other mechanism of survival in acid media, possibly dependent on cell wall properties, in view of its greater cell wall thickness and increased survival in pH-uncontrolled glucose broth in the absence of detectable EPS production. It is postulated that intracellular and extracellular polysaccharide formation, cell wall thickening and reduced viability were indicators of unfavourable growth conditions in the test media. Cariogenic strains of S. mutans appear to be able to survive better under such conditions and hence the prevalence of this and other polysaccharide-producing organisms in stagnant sites in natural dental plaques."}
{"id": "PMID:11397", "title": "Current status of treatment of severe hypertension.", "content": "Drug fashions have changed and older drugs have given place to others with less side effects. Drugs and combinations of drugs administered to 100 patients currently under treatment at a clinic for severe hypertensives are listed. The most popular drugs were thiazide diuretics, methyldopa, beta-adrenergic blocking drugs, clinidine and hydrallazine. A thiazide diuretic was a constant member of the drug combinations. About 60% of patients achieved \"good\" blood pressure control (diastolic blood pressure less than or equal to 100 mm Hg), 30% \"fair\" (diastolic blood pressure=100 to 110 mm Hg) and 10+ \"poor\" (diastolic blood pressure greater than 110 mm Hg). Similar proportions were in \"good\", \"fair\" and \"poor\" general health. The best prospect for improved management of hypertension probably lies in earlier treatment with current drug combinations.", "contents": "Current status of treatment of severe hypertension. Drug fashions have changed and older drugs have given place to others with less side effects. Drugs and combinations of drugs administered to 100 patients currently under treatment at a clinic for severe hypertensives are listed. The most popular drugs were thiazide diuretics, methyldopa, beta-adrenergic blocking drugs, clinidine and hydrallazine. A thiazide diuretic was a constant member of the drug combinations. About 60% of patients achieved \"good\" blood pressure control (diastolic blood pressure less than or equal to 100 mm Hg), 30% \"fair\" (diastolic blood pressure=100 to 110 mm Hg) and 10+ \"poor\" (diastolic blood pressure greater than 110 mm Hg). Similar proportions were in \"good\", \"fair\" and \"poor\" general health. The best prospect for improved management of hypertension probably lies in earlier treatment with current drug combinations."}
{"id": "PMID:11398", "title": "[How healthy are our blood donors? Result of a liver screening in voluntary blood donors of Blutspendedienst Innsbruck].", "content": "A screening of hepatic function and HBs-antigen, made in 22344 voluntary blood donors in the bloodbank of Innsbruck, gave the following results: 0,33% HBs-AG negative donors were found to have pathological liverfunctiontests. Overweight and alcohol would be established as the most important etiological factors. 0,4% of the donors are carriers of the HBs-antigen. A control examination after 2 years showed a persistence of that antigenemia. Antigen carriers are requested to have regular examinations. Since HBs-AG positive hepatitis is not only transferred by blood and blood-constituents, it would be important to use the same screening methods applied in the blood donor organisation throughout any hospital area, to reduce the incidence of this disease.", "contents": "[How healthy are our blood donors? Result of a liver screening in voluntary blood donors of Blutspendedienst Innsbruck]. A screening of hepatic function and HBs-antigen, made in 22344 voluntary blood donors in the bloodbank of Innsbruck, gave the following results: 0,33% HBs-AG negative donors were found to have pathological liverfunctiontests. Overweight and alcohol would be established as the most important etiological factors. 0,4% of the donors are carriers of the HBs-antigen. A control examination after 2 years showed a persistence of that antigenemia. Antigen carriers are requested to have regular examinations. Since HBs-AG positive hepatitis is not only transferred by blood and blood-constituents, it would be important to use the same screening methods applied in the blood donor organisation throughout any hospital area, to reduce the incidence of this disease."}
{"id": "PMID:11409", "title": "Anatomo-pathologic observations on epidemic nephropathy.", "content": "Two cases of necropsy and 5 cases of renal biopuncture were studied on the occassion of an epidemic of \"hemorrhagic fever with renal syndrome\" identified in mountainous areas of Transylvania. The prevalent pathogenic process was capillary toxicosis which injured the renal tubules and vessels. The severity of the disease was determined by the phenomena of tubular failure, by the hemorrhagic syndrome and shock.", "contents": "Anatomo-pathologic observations on epidemic nephropathy. Two cases of necropsy and 5 cases of renal biopuncture were studied on the occassion of an epidemic of \"hemorrhagic fever with renal syndrome\" identified in mountainous areas of Transylvania. The prevalent pathogenic process was capillary toxicosis which injured the renal tubules and vessels. The severity of the disease was determined by the phenomena of tubular failure, by the hemorrhagic syndrome and shock."}
{"id": "PMID:11416", "title": "Effectiveness of various food preservatives in controlling the outgrowth of Byssochlamys nivea ascospores.", "content": "Potassium sorbate, sodium benzoate, sulfur dioxide, and diethylpyrocarbonate (DEPC) were tested for their effectiveness in preventing the outgrowth of Byssochlamys nivea Westling ascospores. Sulfur dioxide was the most inhibitory of the test antimycotics, complete inhibition of colony formation occuring in acidified (pH 3.5) potato dextrose agar containing 50 ppm of the preservative. Complete inhibition of B. nivea ascospore outgrowth in grape juice stored for 60 days was noted in the presence of 300 ppm sulfur dioxide, 400 ppm potassium sorbate, and 600 ppm DEPC. Growth was observed in grape juice containing 1000 ppm sodium benzoate. The presence of up to 100 ppm potassium sorbate in grape juice during heat activation appears to have a stimulatory effect on breaking dormancy, while the other test preservatives at this concentration decrease the heat resistance of B. nivea ascospores. The time elapsed between heat shock and exposure to DEPC or sodium benzoate is critical with respect to the sensitivity of ascospores to these preservatives.", "contents": "Effectiveness of various food preservatives in controlling the outgrowth of Byssochlamys nivea ascospores. Potassium sorbate, sodium benzoate, sulfur dioxide, and diethylpyrocarbonate (DEPC) were tested for their effectiveness in preventing the outgrowth of Byssochlamys nivea Westling ascospores. Sulfur dioxide was the most inhibitory of the test antimycotics, complete inhibition of colony formation occuring in acidified (pH 3.5) potato dextrose agar containing 50 ppm of the preservative. Complete inhibition of B. nivea ascospore outgrowth in grape juice stored for 60 days was noted in the presence of 300 ppm sulfur dioxide, 400 ppm potassium sorbate, and 600 ppm DEPC. Growth was observed in grape juice containing 1000 ppm sodium benzoate. The presence of up to 100 ppm potassium sorbate in grape juice during heat activation appears to have a stimulatory effect on breaking dormancy, while the other test preservatives at this concentration decrease the heat resistance of B. nivea ascospores. The time elapsed between heat shock and exposure to DEPC or sodium benzoate is critical with respect to the sensitivity of ascospores to these preservatives."}
{"id": "PMID:11417", "title": "[Effect of production and storage on the survival of Staphylococcus aureus in curd].", "content": "The effect of curd production on the survival of staphylococci has been studied. At the begining of the manufacture process favourable conditions exist for the development of staphylococci. Their number decreases with the increasing acidity and in the final product they occur only sporadically or quite disappeare, especially when the curd is stored at cooling chamber temperatures. The lactose-positive staphylococci take part in the splitting of milk lactose and the production of milk acid as well. Their participation in this process is statistically significant. Some biochemical properties of the used Staphylococcus aureus strain as plasma koagulation, lecithinase, phosphatase and haemolytical toxin production, glucose, mannitol and lactose fermentation under aerobic and anaerobic conditions were studied. The biochemical properties of this strain do not change during the process of curd production.", "contents": "[Effect of production and storage on the survival of Staphylococcus aureus in curd]. The effect of curd production on the survival of staphylococci has been studied. At the begining of the manufacture process favourable conditions exist for the development of staphylococci. Their number decreases with the increasing acidity and in the final product they occur only sporadically or quite disappeare, especially when the curd is stored at cooling chamber temperatures. The lactose-positive staphylococci take part in the splitting of milk lactose and the production of milk acid as well. Their participation in this process is statistically significant. Some biochemical properties of the used Staphylococcus aureus strain as plasma koagulation, lecithinase, phosphatase and haemolytical toxin production, glucose, mannitol and lactose fermentation under aerobic and anaerobic conditions were studied. The biochemical properties of this strain do not change during the process of curd production."}
{"id": "PMID:11420", "title": "Dexclamol: effects on catecholamine metabolism and demonstration of stereochemical specificity of antagonism of central adrenergic receptors.", "content": "The effects of the benzocycloheptapyridoisoquinolinol derivative (+)-dexclamol-HCl and some of those of (+/-)-dexclamol and the corresponding (-)-dexclamol were compared to those of the potent neuroleptic agents droperidol and fluphenazine on norepinephrine (NE) and dopamine (DA) turnover in the whole brain and in the striatum of rats. Differences in NE and DA depletion following tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine indicated that (+)-dexclamol and droperidol increased DA turnover with no effect on NE turnover. At a higher dose both (+)-dexclamol and droperidol, but not (-)-dexclamol, accelerated DA turnover and also that of NE. A decrease in DA concentration occurred after both drugs under the latter condition only. (+)-Dexclamol, (+/-)-dexclamol and droperidol exhibited a similar onset of action employing striatal homovanillic acid (HVA) increase as indicative of DA turnover changes. The duration of action of droperidol was shorter than for (+)-dexclamol and (+/-)-dexclamol; fluphenazine displayed a slower onset and longer duration of activity. The (-)-dexclamol was ineffective. (+)-Dexclamol, droperidol and phentolamine reduced the concentrations of 3H-NE in heart when given after the 3H-NE, a probable indication of increased NE release due to adrenergic receptor blockade. The present findings demonstrate that the neuroleptic agent (+)-dexclamol, but not (-)-dexclamol, affects central DA and NE turnover and indicates a stereochemical specificity with respect to antagonism of central DA and NE receptors.", "contents": "Dexclamol: effects on catecholamine metabolism and demonstration of stereochemical specificity of antagonism of central adrenergic receptors. The effects of the benzocycloheptapyridoisoquinolinol derivative (+)-dexclamol-HCl and some of those of (+/-)-dexclamol and the corresponding (-)-dexclamol were compared to those of the potent neuroleptic agents droperidol and fluphenazine on norepinephrine (NE) and dopamine (DA) turnover in the whole brain and in the striatum of rats. Differences in NE and DA depletion following tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine indicated that (+)-dexclamol and droperidol increased DA turnover with no effect on NE turnover. At a higher dose both (+)-dexclamol and droperidol, but not (-)-dexclamol, accelerated DA turnover and also that of NE. A decrease in DA concentration occurred after both drugs under the latter condition only. (+)-Dexclamol, (+/-)-dexclamol and droperidol exhibited a similar onset of action employing striatal homovanillic acid (HVA) increase as indicative of DA turnover changes. The duration of action of droperidol was shorter than for (+)-dexclamol and (+/-)-dexclamol; fluphenazine displayed a slower onset and longer duration of activity. The (-)-dexclamol was ineffective. (+)-Dexclamol, droperidol and phentolamine reduced the concentrations of 3H-NE in heart when given after the 3H-NE, a probable indication of increased NE release due to adrenergic receptor blockade. The present findings demonstrate that the neuroleptic agent (+)-dexclamol, but not (-)-dexclamol, affects central DA and NE turnover and indicates a stereochemical specificity with respect to antagonism of central DA and NE receptors."}
{"id": "PMID:11421", "title": "Association between the increase of cAMP content and the trans-synaptic induction of tyrosine hydroxylase in rat adrenal medulla. Studies with dexamethasone and reserpine.", "content": "When dexamethasone 0.25 or 2.5 mumole/kg i.p. was injected 2 h before reserpine (16 mumol/kg i.p.) the time course of the increase in cAMP content of rat adrenal medulla was changed. Reserpine alone caused a monophasic increase lasting between 1-2 h; reserpine after dexamethasone caused a biphasic increase: the immediate response, lasting between 15 and 30 min, was followed by a secondary increase beginning 2-3 h after reserpine and lasting for several hours. The overall increase in cAMP content elicited by reserpine during the 8 h following injection remained unchanged or was even increased, depending on the dose of dexamethasone. Pretreatment with dexamethasone, which delayed the increase in cAMP, also delayed the activation and translocation of protein kinase and the induction of tyrosine hydroxylase caused by reserpine in adrenal medulla. The action of reserpine on the cAMP content of adrenal medulla required an intact innervation and did not appear to be related to increased secretion of ACTH from pituitary. In denervated adrenals reserpine failed to increase the cAMP content of the medulla but not that of the cortex.", "contents": "Association between the increase of cAMP content and the trans-synaptic induction of tyrosine hydroxylase in rat adrenal medulla. Studies with dexamethasone and reserpine. When dexamethasone 0.25 or 2.5 mumole/kg i.p. was injected 2 h before reserpine (16 mumol/kg i.p.) the time course of the increase in cAMP content of rat adrenal medulla was changed. Reserpine alone caused a monophasic increase lasting between 1-2 h; reserpine after dexamethasone caused a biphasic increase: the immediate response, lasting between 15 and 30 min, was followed by a secondary increase beginning 2-3 h after reserpine and lasting for several hours. The overall increase in cAMP content elicited by reserpine during the 8 h following injection remained unchanged or was even increased, depending on the dose of dexamethasone. Pretreatment with dexamethasone, which delayed the increase in cAMP, also delayed the activation and translocation of protein kinase and the induction of tyrosine hydroxylase caused by reserpine in adrenal medulla. The action of reserpine on the cAMP content of adrenal medulla required an intact innervation and did not appear to be related to increased secretion of ACTH from pituitary. In denervated adrenals reserpine failed to increase the cAMP content of the medulla but not that of the cortex."}
{"id": "PMID:11424", "title": "[Controlled clinical trial of parsalmide in patients with predominantly neuro-anxiety syndromes. Comparison with chlordiazepoxide].", "content": "The anxiolytic and tranquillizing effect of a new compound called parsalmide was studied in a group of 20 patients suffering from medium anxiety neurosis. The new drug also possesses anti-inflammatory and analgesic effects. The technique employed was the double blind, between patients, crossover system and chlordiazepoxide was used for comparison purposes. Parsalmide proved to possess an anxiolytic-tranquillizing action comparable to that of chlordiazepoxide and, unlike the latter, was quite free from unpleasant side effects, such as somnolence and asthenia.", "contents": "[Controlled clinical trial of parsalmide in patients with predominantly neuro-anxiety syndromes. Comparison with chlordiazepoxide]. The anxiolytic and tranquillizing effect of a new compound called parsalmide was studied in a group of 20 patients suffering from medium anxiety neurosis. The new drug also possesses anti-inflammatory and analgesic effects. The technique employed was the double blind, between patients, crossover system and chlordiazepoxide was used for comparison purposes. Parsalmide proved to possess an anxiolytic-tranquillizing action comparable to that of chlordiazepoxide and, unlike the latter, was quite free from unpleasant side effects, such as somnolence and asthenia."}
{"id": "PMID:11425", "title": "[Double-blind comparison of parsalmide and diazepam in anxious and depressive neurotic syndromes].", "content": "Parsalmide- a new drug- is effective in the relief of inflammation and pain. In a double-blind, between-patients, cross-over trial with diazepam in 16 subjects with anxiety and depression, however, it proved less successful in relieving anxiety, though it was on a par with diazepam on an overall evaluation. The daytime somnolence and asthenia observed with diazepam were not observed with parsalmide.", "contents": "[Double-blind comparison of parsalmide and diazepam in anxious and depressive neurotic syndromes]. Parsalmide- a new drug- is effective in the relief of inflammation and pain. In a double-blind, between-patients, cross-over trial with diazepam in 16 subjects with anxiety and depression, however, it proved less successful in relieving anxiety, though it was on a par with diazepam on an overall evaluation. The daytime somnolence and asthenia observed with diazepam were not observed with parsalmide."}
{"id": "PMID:11426", "title": "[The problem of dissecting aneurysm of the aorta and its benign course].", "content": "On the basis of a personal case, the clinical, diagnostic and therapeutic problems of variants of dissecting aneurysm of the aorta with benign course are discussed. The usefulness of cardio-aortic angioscintigraphy in the interests of early diagnosis of aneurysm and aortography by catheterism for specifying its location and extent, is pointed out. Spontaneous benign development would seem to be tied up with the affected area of the aorta, the modalities of dissection, and above all with the establishment of a distal return breach for blood flow into the aortic lumen. The predominant role of cystic medionecrosis in determining dissection is stressed and the usefulness of intensive pharmacological therapy based essentially on hypotensive and beta-blocking substances confirmed.", "contents": "[The problem of dissecting aneurysm of the aorta and its benign course]. On the basis of a personal case, the clinical, diagnostic and therapeutic problems of variants of dissecting aneurysm of the aorta with benign course are discussed. The usefulness of cardio-aortic angioscintigraphy in the interests of early diagnosis of aneurysm and aortography by catheterism for specifying its location and extent, is pointed out. Spontaneous benign development would seem to be tied up with the affected area of the aorta, the modalities of dissection, and above all with the establishment of a distal return breach for blood flow into the aortic lumen. The predominant role of cystic medionecrosis in determining dissection is stressed and the usefulness of intensive pharmacological therapy based essentially on hypotensive and beta-blocking substances confirmed."}
{"id": "PMID:11431", "title": "[Temperature measurements in Wistar rats and DS carcinosarcoma under various conditions].", "content": "Temperature measurements on Wistar rats with miniature-Hg-thermometer and laser-welded thermoelements lead to the following conclusions: 1. No change of temperature-profile, especially in the liver through glucose-infusion and hyperthermia, can be noticed. 2. Glucose-infusion causes hyperthermia of about 1.5 degrees C. 3. The temperature of the subcutaneous growing DS- carcinosarcoma lies under the norm and increases with the distance from the surface of the body. 4. Hyperthermia of 3 degrees C has no influence on tumor over-acidification. 5. The substance CEU has no pyrogenic effect on the rat but potentiates the decrease of the body-temperature caused by narcosis.", "contents": "[Temperature measurements in Wistar rats and DS carcinosarcoma under various conditions]. Temperature measurements on Wistar rats with miniature-Hg-thermometer and laser-welded thermoelements lead to the following conclusions: 1. No change of temperature-profile, especially in the liver through glucose-infusion and hyperthermia, can be noticed. 2. Glucose-infusion causes hyperthermia of about 1.5 degrees C. 3. The temperature of the subcutaneous growing DS- carcinosarcoma lies under the norm and increases with the distance from the surface of the body. 4. Hyperthermia of 3 degrees C has no influence on tumor over-acidification. 5. The substance CEU has no pyrogenic effect on the rat but potentiates the decrease of the body-temperature caused by narcosis."}
{"id": "PMID:11432", "title": "Polyarteritis nodosa induced in arteriosclerotic, male and female breeder rats by chronic alloxan diabetes.", "content": "Male and female virgin rats and breeder rats with naturally-occurring diabetes, hypertension and arteriosclerosis, were made severely diabetic with a single, subcutaneous injection of alloxan (10 mg/100 g b.w.), after an 18 h fast. During five months of unrelenting diabetes, some animals became obese while others became emaciated. Only the emaciated animals survived but they were blind, their adrenal glands were hemorrhagic, hypertrophied and thrombosed, thymi involuted, kidneys swollen, hearts reduced in size while testes and ovaries were atrophic. Serum CPK, SGOT and SGPT were elevated concomitant with extensive cardiovascular damage, hepatic steatosis and generalized catabolism. Circulating triglycerides and free fatty acids were markedly elevated with total cholesterol only slightly increased. BUN and serum calcium levels were also greatly elevated. Sub-normal Cmpd. B levels indicated impaired adrenal steroidogenesis. Virgin rats developed arteriosclerosis and male and female breeder rats showed exacerbation of their pre-existing aortic sclerosis as well as P.A.N. lesions in their small-sized arteries. It is believed that severe diabetes causes exacerbation of the endogenous hormonal milieu resulting from abnormal hypothalamic-pituitary-adrenal function induced by repeated breeding, which conditions the connective tissue components of the arterial wall of rats toward accelerated degenerative changes.", "contents": "Polyarteritis nodosa induced in arteriosclerotic, male and female breeder rats by chronic alloxan diabetes. Male and female virgin rats and breeder rats with naturally-occurring diabetes, hypertension and arteriosclerosis, were made severely diabetic with a single, subcutaneous injection of alloxan (10 mg/100 g b.w.), after an 18 h fast. During five months of unrelenting diabetes, some animals became obese while others became emaciated. Only the emaciated animals survived but they were blind, their adrenal glands were hemorrhagic, hypertrophied and thrombosed, thymi involuted, kidneys swollen, hearts reduced in size while testes and ovaries were atrophic. Serum CPK, SGOT and SGPT were elevated concomitant with extensive cardiovascular damage, hepatic steatosis and generalized catabolism. Circulating triglycerides and free fatty acids were markedly elevated with total cholesterol only slightly increased. BUN and serum calcium levels were also greatly elevated. Sub-normal Cmpd. B levels indicated impaired adrenal steroidogenesis. Virgin rats developed arteriosclerosis and male and female breeder rats showed exacerbation of their pre-existing aortic sclerosis as well as P.A.N. lesions in their small-sized arteries. It is believed that severe diabetes causes exacerbation of the endogenous hormonal milieu resulting from abnormal hypothalamic-pituitary-adrenal function induced by repeated breeding, which conditions the connective tissue components of the arterial wall of rats toward accelerated degenerative changes."}
{"id": "PMID:11434", "title": "Conditioning of striatal dopamine metabolism with methadone, morphine or bulbocapnine as an unconditioned stimulus.", "content": "Psychotropic drugs such as methadone, morphine and bulbocapnine produce increments in dopamine metabolism as an unconditioned reflex. When a buzzer noise is used as a conditioned stimulus (CS) with these drugs as unconditioned stimuli, the buzzer CS acquires the properties of the drugs in increasing dopamine metabolism. These results suggest that the brain, like other visceral organs, can be conditioned in terms of neurotransmitter release or metabolism.", "contents": "Conditioning of striatal dopamine metabolism with methadone, morphine or bulbocapnine as an unconditioned stimulus. Psychotropic drugs such as methadone, morphine and bulbocapnine produce increments in dopamine metabolism as an unconditioned reflex. When a buzzer noise is used as a conditioned stimulus (CS) with these drugs as unconditioned stimuli, the buzzer CS acquires the properties of the drugs in increasing dopamine metabolism. These results suggest that the brain, like other visceral organs, can be conditioned in terms of neurotransmitter release or metabolism."}
{"id": "PMID:11442", "title": "Arterial and mixed venous PCO2 and hydrogen ion, bicarbonate and base excess concentrations in water-depleted dogs.", "content": "The arterial (a), mixed venous (v), and arterial-mixed venous differences (A-V) of hydrogen ion concentration ([H+]), PCO2, HCO-3 and base excess (BE) were measured during 3 h in control (C), water-depleted (WD) and water- and salt-depleted (WSD) dogs. In WD animals the difference in hydrogen ion concentration between venous and arterial blood increased because the [H+] increased more in venous than in arterial blood. In WSD animals (A-V) [H+] remained unchanged since both [H+]a and [H+]v increases were parallel. [H+] variations seem to represent the changes in fixed-acid concentration of blood. The difference between both groups of animals in (A-V) [H+] changes could be ascribed to PCO2 variations. [HCO-3] values changed inconsistently. Arterial samples from the experimental groups showed a continuous decrease at the same rate of change. The mean values in WSD were lower than in WD. [HCO-3]v of WSD decreased slowly during the experiment. The rate of decrease of (A-V) [HCO-3] was higher in WD than in WSD. The different behavior of of [HCO-3] between both arterial and mixed venous samples and among experimental groups disappeared if [HCO-3] changes were corrected for bicarbonate generation due to PCO2 variation (respiratory bicarbonate). Thus [HCO-3] corrected for PCO2 variation represents metabolic changes, in good agreement with both [H+] and BE variations. The metabolic acidosis cannot be explained only on the basis of the increase in blood lactate; it is suggested that other fixed acids might contribute to the decrease in blood bicarbonate. In both experimental groups PvCO2 increased continuously. The (A-V) PCO2 showed the same rate of change. There is a good relationship between this increase and the degree of plasma volume change. It therefore might be that PvCO2 increase is a direct consequence of hemodynamic impairment. In WD and WSD, BE decreased progressively in both arterial and mixed venous samples. BEa values were lower than BEv values after the experiment began. (A-V) BE decreased in an exponential manner in both experimental groups; this change could be ascribed to the increased level of deoxygenated hemoglobin in mixed venous blood, thus giving rise to a decrease in fixed acid concentration.", "contents": "Arterial and mixed venous PCO2 and hydrogen ion, bicarbonate and base excess concentrations in water-depleted dogs. The arterial (a), mixed venous (v), and arterial-mixed venous differences (A-V) of hydrogen ion concentration ([H+]), PCO2, HCO-3 and base excess (BE) were measured during 3 h in control (C), water-depleted (WD) and water- and salt-depleted (WSD) dogs. In WD animals the difference in hydrogen ion concentration between venous and arterial blood increased because the [H+] increased more in venous than in arterial blood. In WSD animals (A-V) [H+] remained unchanged since both [H+]a and [H+]v increases were parallel. [H+] variations seem to represent the changes in fixed-acid concentration of blood. The difference between both groups of animals in (A-V) [H+] changes could be ascribed to PCO2 variations. [HCO-3] values changed inconsistently. Arterial samples from the experimental groups showed a continuous decrease at the same rate of change. The mean values in WSD were lower than in WD. [HCO-3]v of WSD decreased slowly during the experiment. The rate of decrease of (A-V) [HCO-3] was higher in WD than in WSD. The different behavior of of [HCO-3] between both arterial and mixed venous samples and among experimental groups disappeared if [HCO-3] changes were corrected for bicarbonate generation due to PCO2 variation (respiratory bicarbonate). Thus [HCO-3] corrected for PCO2 variation represents metabolic changes, in good agreement with both [H+] and BE variations. The metabolic acidosis cannot be explained only on the basis of the increase in blood lactate; it is suggested that other fixed acids might contribute to the decrease in blood bicarbonate. In both experimental groups PvCO2 increased continuously. The (A-V) PCO2 showed the same rate of change. There is a good relationship between this increase and the degree of plasma volume change. It therefore might be that PvCO2 increase is a direct consequence of hemodynamic impairment. In WD and WSD, BE decreased progressively in both arterial and mixed venous samples. BEa values were lower than BEv values after the experiment began. (A-V) BE decreased in an exponential manner in both experimental groups; this change could be ascribed to the increased level of deoxygenated hemoglobin in mixed venous blood, thus giving rise to a decrease in fixed acid concentration."}
{"id": "PMID:11443", "title": "Developmental changes of sugar transport in the ovine small intestine.", "content": "Intestinal monosaccharide transport was studied in young lambs (age: up to 1 week) and in older lambs (age: 2.5-4 months) with well developed forestomach system employing everted sacs of small intestine. Both glucose and galactose were transported against a high concentration gradient from the mucosal to the serosal side of the intestinal wall in young lambs. In the older lambs glucose was transported only against a small concentration gradient, when intestinal glucose metabolism was diminished by reducing the pH of the incubation medium from 7 to 5. Galactose and alpha-methyl-glucoside, which are not markedly metabolized by the intestine, were transported against a small but similar concentration gradient at both pH values in these animals. In young lambs, however, at pH 5 intestinal galactose transport was lower than at pH 7. These results indicate that active intestinal monosaccharide transport becomes rudimentary in the maturing sheep.", "contents": "Developmental changes of sugar transport in the ovine small intestine. Intestinal monosaccharide transport was studied in young lambs (age: up to 1 week) and in older lambs (age: 2.5-4 months) with well developed forestomach system employing everted sacs of small intestine. Both glucose and galactose were transported against a high concentration gradient from the mucosal to the serosal side of the intestinal wall in young lambs. In the older lambs glucose was transported only against a small concentration gradient, when intestinal glucose metabolism was diminished by reducing the pH of the incubation medium from 7 to 5. Galactose and alpha-methyl-glucoside, which are not markedly metabolized by the intestine, were transported against a small but similar concentration gradient at both pH values in these animals. In young lambs, however, at pH 5 intestinal galactose transport was lower than at pH 7. These results indicate that active intestinal monosaccharide transport becomes rudimentary in the maturing sheep."}
{"id": "PMID:11444", "title": "Blood gas analyses of hibernating hamsters and dormice.", "content": "Blood gases were measured in hibernating and hypothermic animals as a biological model of clinical hypothermia. Blood gas analyses from hamsters and dormice were carried out with the aid of permanent arterial catheters during normothermia and hibernation. In golden hamster pH increased from 7.30 to 7.46 during hibernation and PaCO2 decreased from 59.7 to 40.5 mm Hg. In dormice pH increased from 7.24 to 7.44 and PaCO2 decreases from 38.5 to 27.4 mm Hg. The actual bicarbonate concentration increased from 29 to 52 mMol in golden hamsters and from 16 to 34 mMol in dormice during hibernation. In experiments with induced hypothermia in golden hamsters under ketamine-anaesthesia there was no correlation between temperature and PaCO2. Despite the slight decrease in PaCO2 during hibernation we conclude that PaCO2 rather than total carbon dioxide content is held constant when temperature is changed. During clinical hypothermia it will probably be safe to keep PaCO2 constant.", "contents": "Blood gas analyses of hibernating hamsters and dormice. Blood gases were measured in hibernating and hypothermic animals as a biological model of clinical hypothermia. Blood gas analyses from hamsters and dormice were carried out with the aid of permanent arterial catheters during normothermia and hibernation. In golden hamster pH increased from 7.30 to 7.46 during hibernation and PaCO2 decreased from 59.7 to 40.5 mm Hg. In dormice pH increased from 7.24 to 7.44 and PaCO2 decreases from 38.5 to 27.4 mm Hg. The actual bicarbonate concentration increased from 29 to 52 mMol in golden hamsters and from 16 to 34 mMol in dormice during hibernation. In experiments with induced hypothermia in golden hamsters under ketamine-anaesthesia there was no correlation between temperature and PaCO2. Despite the slight decrease in PaCO2 during hibernation we conclude that PaCO2 rather than total carbon dioxide content is held constant when temperature is changed. During clinical hypothermia it will probably be safe to keep PaCO2 constant."}
{"id": "PMID:11445", "title": "(Na+K+)-activated ATPase in human cornea. Distribution within the cornea and properties of the enzyme from epithelial cells.", "content": "Distribution and principal characteristics of (Na+K+)-activated ATPase in human cornea were investigated. (Na+K+)-ATPase was present in both epithelium and endothelium, whereas the corneal stroma did not exhibit significant enzyme activity. In homogenates specific activity of the (Na+K+)-ATPase was 2.3-fold higher in endothelium than in epithelium. Calculation of total enzyme activity revealed a 6.1-fold higher content of (Na+K+)-ATPase in the epithelium. In the epithelium a 7-fold enrichment of (Na+K+)-ATPase compared to the homogenate was obtained in the 150-1500 X gav fraction. Maximum enrichment in the endothelium was 3.5-fold and was achieved in the 1500-2500 X gav fraction. Both fractions showed, however, the same specific activity. The pH-optimum of (Na+K+)-ATPase in the 150-1500 X gav fraction ranged from 8.0-8.2 in both epithelium and endothelium. In the epithelial 150-1500 X gav fraction the apparent Km-values were 4.0 mM for Na+, 2.8 mM for K+ and 0.12 mM for Mg2+ - ATP in equimolar concentrations. The inhibition constant of epithelial (Na+K+)-ATPase for ouabain was determined as Ki = 3.3 X 10(-7) M. The present data support the view that control of corneal hydration in man is a function of both endothelium and epithelium.", "contents": "(Na+K+)-activated ATPase in human cornea. Distribution within the cornea and properties of the enzyme from epithelial cells. Distribution and principal characteristics of (Na+K+)-activated ATPase in human cornea were investigated. (Na+K+)-ATPase was present in both epithelium and endothelium, whereas the corneal stroma did not exhibit significant enzyme activity. In homogenates specific activity of the (Na+K+)-ATPase was 2.3-fold higher in endothelium than in epithelium. Calculation of total enzyme activity revealed a 6.1-fold higher content of (Na+K+)-ATPase in the epithelium. In the epithelium a 7-fold enrichment of (Na+K+)-ATPase compared to the homogenate was obtained in the 150-1500 X gav fraction. Maximum enrichment in the endothelium was 3.5-fold and was achieved in the 1500-2500 X gav fraction. Both fractions showed, however, the same specific activity. The pH-optimum of (Na+K+)-ATPase in the 150-1500 X gav fraction ranged from 8.0-8.2 in both epithelium and endothelium. In the epithelial 150-1500 X gav fraction the apparent Km-values were 4.0 mM for Na+, 2.8 mM for K+ and 0.12 mM for Mg2+ - ATP in equimolar concentrations. The inhibition constant of epithelial (Na+K+)-ATPase for ouabain was determined as Ki = 3.3 X 10(-7) M. The present data support the view that control of corneal hydration in man is a function of both endothelium and epithelium."}
{"id": "PMID:11446", "title": "Effect of oxygen saturation on H+ and Cl- distribution across the red cell membrane in human and ruminant blood.", "content": "Alterations of red cell pH (pHc) and distribution ratios of H+ (gammaH+) and Cl (gammaCl-) between plasma and red blood cells with oxygenation of blood were studied in human blood (audult and fetal) and ruminant blood (bovine, goat and sheep). The experiments were carried out at a plasma pH of 7.0 to 7.7 and at 37 degrees C. In human blood pHc of fully oxygenated blood was 0.035 pH lower than that of fully deoxygenated blood in all ranges of plasma pH studied. In ruminant blood, however, the differences in pHc between oxygenated and deoxygenated blood were 0.011 in ox, and 0.003 in goat and sheep, all of them not being significant. The decreases in gammaH+ accompanying oxygenation were in fairly good agreement with those in gammaCl- in human blood and amounted to about 0.05. In ruminant blood, in spite of virtually zero changes in gammaH+ with oxygenation, the decreases in gammaCl- were slightly greater than those in human blood. There might be a species difference in the mechanisms of distribution of Cl- and H+ across the red cell membrane.", "contents": "Effect of oxygen saturation on H+ and Cl- distribution across the red cell membrane in human and ruminant blood. Alterations of red cell pH (pHc) and distribution ratios of H+ (gammaH+) and Cl (gammaCl-) between plasma and red blood cells with oxygenation of blood were studied in human blood (audult and fetal) and ruminant blood (bovine, goat and sheep). The experiments were carried out at a plasma pH of 7.0 to 7.7 and at 37 degrees C. In human blood pHc of fully oxygenated blood was 0.035 pH lower than that of fully deoxygenated blood in all ranges of plasma pH studied. In ruminant blood, however, the differences in pHc between oxygenated and deoxygenated blood were 0.011 in ox, and 0.003 in goat and sheep, all of them not being significant. The decreases in gammaH+ accompanying oxygenation were in fairly good agreement with those in gammaCl- in human blood and amounted to about 0.05. In ruminant blood, in spite of virtually zero changes in gammaH+ with oxygenation, the decreases in gammaCl- were slightly greater than those in human blood. There might be a species difference in the mechanisms of distribution of Cl- and H+ across the red cell membrane."}
{"id": "PMID:11449", "title": "CD studies on the conformation of oligonucleotides complexed with divalent metal ions: interaction of Zn2+ with guanine favours syn conformation.", "content": "The interaction of the divalent metal ions Mg2+, Mn2+, Zn2+ and Cu2+ with GpG and several other dinucleoside monophosphates were investigated by means of circular dichroism. The spectra of the complexes of GpG, GpU analogues and ApGpG caused in the presence of Zn2+ and other transition metals show a close similarity in the spectral CD shape to that previously reported in the literature for GpG and GpU at low pH and for m7GpG. From the results it may be concluded that transition metal ions-particularly considered for Zn2+/- tends to favour the degree of stacking with Guo in syn conformation in GpG or GpU due to the coordination of the metal ion at N-7 of the 3'-bound position while shielding of the phosphate site by Mg2+ does not influence the sugar-base torsional angle under comparable conditions. Stereochemical aspects and selectivity of the Zn2+ mediated conformation of the dinucleoside phosphates are discussed.", "contents": "CD studies on the conformation of oligonucleotides complexed with divalent metal ions: interaction of Zn2+ with guanine favours syn conformation. The interaction of the divalent metal ions Mg2+, Mn2+, Zn2+ and Cu2+ with GpG and several other dinucleoside monophosphates were investigated by means of circular dichroism. The spectra of the complexes of GpG, GpU analogues and ApGpG caused in the presence of Zn2+ and other transition metals show a close similarity in the spectral CD shape to that previously reported in the literature for GpG and GpU at low pH and for m7GpG. From the results it may be concluded that transition metal ions-particularly considered for Zn2+/- tends to favour the degree of stacking with Guo in syn conformation in GpG or GpU due to the coordination of the metal ion at N-7 of the 3'-bound position while shielding of the phosphate site by Mg2+ does not influence the sugar-base torsional angle under comparable conditions. Stereochemical aspects and selectivity of the Zn2+ mediated conformation of the dinucleoside phosphates are discussed."}
{"id": "PMID:11454", "title": "Pretreatment with antilymphocyte globulin and donor cells on graft prolongation in an experimental model and some observations on graft-versus-host reaction.", "content": "Survival of Lewis X Brown Norway F1 renal allografts was prolonged in Lewis recipients by pretreatment with small numbers of donor marrow cells and low dose antilymphocyte globulin(ALG)in combination. Either marrow cells or ALG alone were ineffective at these doses. It was also shown that pretreatment with marrow cells and antilymphocyte serum (ALS) considerably suppressed the local graft-versus-host reaction.", "contents": "Pretreatment with antilymphocyte globulin and donor cells on graft prolongation in an experimental model and some observations on graft-versus-host reaction. Survival of Lewis X Brown Norway F1 renal allografts was prolonged in Lewis recipients by pretreatment with small numbers of donor marrow cells and low dose antilymphocyte globulin(ALG)in combination. Either marrow cells or ALG alone were ineffective at these doses. It was also shown that pretreatment with marrow cells and antilymphocyte serum (ALS) considerably suppressed the local graft-versus-host reaction."}
{"id": "PMID:11455", "title": "The elective treatment of graft-versus-host disease following a bone marrow graft from a father to a son with severe combined immunodeficiency.", "content": "The details of the first successful bone marrow graft from father to son are described. The recipient developed an acute graft-versus-host reaction on the seventh day which was successfully treated with anit-lymphocyte globulin and methotrexate. This regime did not destroy the graft and the child is alive and well with normal immunological function some 2 1/2 years later.", "contents": "The elective treatment of graft-versus-host disease following a bone marrow graft from a father to a son with severe combined immunodeficiency. The details of the first successful bone marrow graft from father to son are described. The recipient developed an acute graft-versus-host reaction on the seventh day which was successfully treated with anit-lymphocyte globulin and methotrexate. This regime did not destroy the graft and the child is alive and well with normal immunological function some 2 1/2 years later."}
{"id": "PMID:11456", "title": "Use of antithymocyte serum in clinical and experimental marrow transplantation.", "content": "Pre-sensitization was investigated in the dog marrow transplant model with donor and recipient mismatching at the canine major histocompatibility complex (MHC). Various prophylactic immunosuppressive regimes were used and it was concluded from these regimes that sensitization to histocompatibility antigens could be abrogated by a combination of procarbazine and antithymocyte serum (ATS) together, before total body irradiation. Subsequent work in humans showed that rejection of a bone marrow graft can be successfully treated by using the procarbazine-antithymocyte clobulin regime and a second transplant. Based upon animal studies, attempts were made to prevent graft-versus-host disease in humans by the use of methotrexate following grafting. Despite matching at the MHC and the use of methotrexate some recipients developed graft-versus-host disease with a fatal outcome. Further work using ATS in the immediate pre- and post-grafting period was inconclusive. Accordingly ATS was used in animals once graft-versus-host disease became manifest with drmatic improvement in clinical status. As a result it was decided to treat all patients who developed graft-versus-host disease with antithymocyte globulin (ATG). Under ATG therpy twelve out of nineteen patients showed complete resolution, and five showed improvement. Six patients became long term survivors. Of the remaining 13, 11 died on interstitial pneumonitis, and two of fungal and bacterial infections. ATG in estblished graft-versus-host disease appears capable of modigying an otherwise fatal disease in a therpeutically beneficial manner.", "contents": "Use of antithymocyte serum in clinical and experimental marrow transplantation. Pre-sensitization was investigated in the dog marrow transplant model with donor and recipient mismatching at the canine major histocompatibility complex (MHC). Various prophylactic immunosuppressive regimes were used and it was concluded from these regimes that sensitization to histocompatibility antigens could be abrogated by a combination of procarbazine and antithymocyte serum (ATS) together, before total body irradiation. Subsequent work in humans showed that rejection of a bone marrow graft can be successfully treated by using the procarbazine-antithymocyte clobulin regime and a second transplant. Based upon animal studies, attempts were made to prevent graft-versus-host disease in humans by the use of methotrexate following grafting. Despite matching at the MHC and the use of methotrexate some recipients developed graft-versus-host disease with a fatal outcome. Further work using ATS in the immediate pre- and post-grafting period was inconclusive. Accordingly ATS was used in animals once graft-versus-host disease became manifest with drmatic improvement in clinical status. As a result it was decided to treat all patients who developed graft-versus-host disease with antithymocyte globulin (ATG). Under ATG therpy twelve out of nineteen patients showed complete resolution, and five showed improvement. Six patients became long term survivors. Of the remaining 13, 11 died on interstitial pneumonitis, and two of fungal and bacterial infections. ATG in estblished graft-versus-host disease appears capable of modigying an otherwise fatal disease in a therpeutically beneficial manner."}
{"id": "PMID:11465", "title": "Immobilization of bacterial luciferase and FMN reductase on glass rods.", "content": "Bacterial luciferase and NAD(P)H: FMN oxidoreductase isolated from Beneckea harveyi were covalently linked via diazotization to arylamine porous glass beads which had been cemented onto plain glass rods. These immobilized enzymes are individually active and also function to produce light via a coupled reaction utilizing NADH or NADPH. These enzymes have properties similar to the soluble forms with regard to pH and substrate optima and also exhibit linearity in peak intensity of the initial flash of light emitted as a function of NADH or NADPH concentration. Linearity with NADH is obtained in the range of 1 pmol to 50 nmol, and between 10 pmol to 200 nmol for NADPH. The bound enzymes are stable and reusable. This immobilized system offers a rapid and inexpensive m", "contents": "Immobilization of bacterial luciferase and FMN reductase on glass rods. Bacterial luciferase and NAD(P)H: FMN oxidoreductase isolated from Beneckea harveyi were covalently linked via diazotization to arylamine porous glass beads which had been cemented onto plain glass rods. These immobilized enzymes are individually active and also function to produce light via a coupled reaction utilizing NADH or NADPH. These enzymes have properties similar to the soluble forms with regard to pH and substrate optima and also exhibit linearity in peak intensity of the initial flash of light emitted as a function of NADH or NADPH concentration. Linearity with NADH is obtained in the range of 1 pmol to 50 nmol, and between 10 pmol to 200 nmol for NADPH. The bound enzymes are stable and reusable. This immobilized system offers a rapid and inexpensive m"}
{"id": "PMID:11466", "title": "Subcellular localization of S-adenosyl-L-methionine:tRNA methyltransferases with aminoacyl-tRNA synthetases in human and mouse: normal and leukemic leukocytes.", "content": "The subcellular distributions of S-adenosyl-L-methionine:tRNA methyltransferases and aminoacyl-tRNA synthetases were investigated with the use of human and mouse normal and leukemic leukocyte cell lines. Differential centrifugation of homogenized cell suspensions produced three pelleted subcellular fractions (nuclear and membrane, microsomal, and postribosomal) and a supernatant fraction. Each fraction was assayed for both methyltransferase activity and synthetase activity. The largest amounts, 40-50%, of total methyltransferase and synthetase activities were localized in either the microsomal or the postribosomal fractions, depending on cell type. In addition, the highest specific activities of these two enzyme systems were found to be present in the microsomal and postribosomal fractions. The psotribosomal fraction from leukemic leukocytes had a methyltransferase specific activity higher than that of the microsomal fraction, while the same two fractions of normal leukocytes had approximately equal activities. Specific activities of aminoacyl-tRNA synthetases were found to be approximately equal for these two fractions, whether they were from normal or leukemic leukocytes. The activity of tRNA methyltransferases and synthetases within the postribosomal fraction of the cytoplasm suggests the existence of high-molecular-weight enzyme complexes for the modification as well as the aminoacylation of tRNA.", "contents": "Subcellular localization of S-adenosyl-L-methionine:tRNA methyltransferases with aminoacyl-tRNA synthetases in human and mouse: normal and leukemic leukocytes. The subcellular distributions of S-adenosyl-L-methionine:tRNA methyltransferases and aminoacyl-tRNA synthetases were investigated with the use of human and mouse normal and leukemic leukocyte cell lines. Differential centrifugation of homogenized cell suspensions produced three pelleted subcellular fractions (nuclear and membrane, microsomal, and postribosomal) and a supernatant fraction. Each fraction was assayed for both methyltransferase activity and synthetase activity. The largest amounts, 40-50%, of total methyltransferase and synthetase activities were localized in either the microsomal or the postribosomal fractions, depending on cell type. In addition, the highest specific activities of these two enzyme systems were found to be present in the microsomal and postribosomal fractions. The psotribosomal fraction from leukemic leukocytes had a methyltransferase specific activity higher than that of the microsomal fraction, while the same two fractions of normal leukocytes had approximately equal activities. Specific activities of aminoacyl-tRNA synthetases were found to be approximately equal for these two fractions, whether they were from normal or leukemic leukocytes. The activity of tRNA methyltransferases and synthetases within the postribosomal fraction of the cytoplasm suggests the existence of high-molecular-weight enzyme complexes for the modification as well as the aminoacylation of tRNA."}
{"id": "PMID:11462", "title": "[Preparative isolation of terrilytin components and study of their enzymatic properties].", "content": "By ion-exchange chromatography the composition of the fibrinolytic enzyme from Aspergillus terricola-terrilytine-was studied. The preparation contained five components that differed in their substrate specificity. Three of the components and proteolytic and fibrinolytic activities. The isolated fractions were examined with respect to their pH stability, pH optima (casein, hemoglobin and fibrin used as substrates), fibrinolytic and fibrinohenolytic activities.", "contents": "[Preparative isolation of terrilytin components and study of their enzymatic properties]. By ion-exchange chromatography the composition of the fibrinolytic enzyme from Aspergillus terricola-terrilytine-was studied. The preparation contained five components that differed in their substrate specificity. Three of the components and proteolytic and fibrinolytic activities. The isolated fractions were examined with respect to their pH stability, pH optima (casein, hemoglobin and fibrin used as substrates), fibrinolytic and fibrinohenolytic activities."}
{"id": "PMID:11508", "title": "Alterations in the behavioral effects of LSD by motivational and neurohumoral variables.", "content": "Forty naive male albino rats were trained to press a bar on a fixed-ratio (FR 32) schedule of water reinforcement. They were then divided into two groups, one of which (N = 20) received 5 min of extra water 12 hr before each experimental session; the other group (N = 20) received no extra water. Half of the animals in each group was given three daily doses (100 mg/kg) of the trytophan hydroxylase inhibitor p-chlorophenylalanine methyl ester (PCPA) while the remaining animals were given control injections of the PCPA vehicle. Ten days following the last administration of PCPA (or vehicle) all animals were given a low dose of LSD (20 mug/kg). Bar-pressing behavior was significantly disrupted only in those animals receiving both PCPA and extra water. Central (whold brain) concentrations of serotonin (5-HT) were significantly lower in all animals which had been treated with PCPA. These results, along with those previously reported, suggest that amount of deprivation can be an important determinant of both the ability of drugs to alter behavior and the dependence of such alterations upon underlying neuronal activity.", "contents": "Alterations in the behavioral effects of LSD by motivational and neurohumoral variables. Forty naive male albino rats were trained to press a bar on a fixed-ratio (FR 32) schedule of water reinforcement. They were then divided into two groups, one of which (N = 20) received 5 min of extra water 12 hr before each experimental session; the other group (N = 20) received no extra water. Half of the animals in each group was given three daily doses (100 mg/kg) of the trytophan hydroxylase inhibitor p-chlorophenylalanine methyl ester (PCPA) while the remaining animals were given control injections of the PCPA vehicle. Ten days following the last administration of PCPA (or vehicle) all animals were given a low dose of LSD (20 mug/kg). Bar-pressing behavior was significantly disrupted only in those animals receiving both PCPA and extra water. Central (whold brain) concentrations of serotonin (5-HT) were significantly lower in all animals which had been treated with PCPA. These results, along with those previously reported, suggest that amount of deprivation can be an important determinant of both the ability of drugs to alter behavior and the dependence of such alterations upon underlying neuronal activity."}
{"id": "PMID:11512", "title": "The organization of perpendicular fibre pathways in the insect optic lobe.", "content": "High resolution serial photomicrography has been used to plot the axonal projection patterns between retina, lamina and medulla in the optic lobes of various insects with differing ommatidial receptor arrangements. Observations are reported on the cabbage white and skipper butterflies, the bee, locust, fly, backswimmer and waterbug. The patterns of these fibre pathways have previously eluded non-rigorous analyses primarily because of their physical dimensions but are revealed in this study to have striking precision and uniformity between species when examined at the level of individually identifiable cells. Axon bundles of the tracts between retina and lamina or lamina and medulla project between a single ommatidium and its corresponding lamina cartridge or between corresponding lamina and medulla cartridges. Lateral interweaving of axons between adjacent bundles is absent. The bundles preserve the retinotopic order within their total array, so transferring the pattern of retinulae directly upon the lamina and thence after horizontal inversion in the chiasma upon the medulla. Within the lamina neuropile on the other hand the trajectories of the individual terminals from a bundle have patterns which are species-specific, sometimes involving lateral divergences. In species with open-rhabdomere ommatidia the terminals distribute to a group of lamina cartidges with a pattern which resembles the receptor pattern in the overlying ommatidium. In species with fused-rhabdome ommatidia the terminals of a single retinula behave less interestingly and all enter the same cartridge, within which, again, each occupies a position related to its cell body position within the retinula. Long visual fibres in both eye types penetrate the lamina and terminate in the particular medulla cartridge that connects with the lamina cartridge underlying their ommatidium. The perpendicular fibre pathways therefore project the visual field exactly upon the medulla in all species while the lack of interweaving between adjacent fibre bundles precludes their involvement in lateral interactions between pathways with differing visual axes. Uniformity of these projection patterns between cell layers and species differences in retinular terminal locations in the lamina can be correlated with different modes of axon growth between and within neuropile layers during optic lobe neurogenesis. Further discussion surrounds the question of which particular receptors give rise to which type of axon, for which no clear generalization has yet emerged.", "contents": "The organization of perpendicular fibre pathways in the insect optic lobe. High resolution serial photomicrography has been used to plot the axonal projection patterns between retina, lamina and medulla in the optic lobes of various insects with differing ommatidial receptor arrangements. Observations are reported on the cabbage white and skipper butterflies, the bee, locust, fly, backswimmer and waterbug. The patterns of these fibre pathways have previously eluded non-rigorous analyses primarily because of their physical dimensions but are revealed in this study to have striking precision and uniformity between species when examined at the level of individually identifiable cells. Axon bundles of the tracts between retina and lamina or lamina and medulla project between a single ommatidium and its corresponding lamina cartridge or between corresponding lamina and medulla cartridges. Lateral interweaving of axons between adjacent bundles is absent. The bundles preserve the retinotopic order within their total array, so transferring the pattern of retinulae directly upon the lamina and thence after horizontal inversion in the chiasma upon the medulla. Within the lamina neuropile on the other hand the trajectories of the individual terminals from a bundle have patterns which are species-specific, sometimes involving lateral divergences. In species with open-rhabdomere ommatidia the terminals distribute to a group of lamina cartidges with a pattern which resembles the receptor pattern in the overlying ommatidium. In species with fused-rhabdome ommatidia the terminals of a single retinula behave less interestingly and all enter the same cartridge, within which, again, each occupies a position related to its cell body position within the retinula. Long visual fibres in both eye types penetrate the lamina and terminate in the particular medulla cartridge that connects with the lamina cartridge underlying their ommatidium. The perpendicular fibre pathways therefore project the visual field exactly upon the medulla in all species while the lack of interweaving between adjacent fibre bundles precludes their involvement in lateral interactions between pathways with differing visual axes. Uniformity of these projection patterns between cell layers and species differences in retinular terminal locations in the lamina can be correlated with different modes of axon growth between and within neuropile layers during optic lobe neurogenesis. Further discussion surrounds the question of which particular receptors give rise to which type of axon, for which no clear generalization has yet emerged."}
{"id": "PMID:11513", "title": "The evolution of plants and animals under domestication: the contribution of studies at the molecular level.", "content": "Protein molecules are essential catalysts in life processes and also form much of the substance of living material. Their three dimensional structures determine their biological function. Their biosynthesis is primarily determined by arrays of nucleic acid macromolecules (DNA and RNA), and the amino acid sequences that constitute their long spatially organized peptide-chain molecules reflect at one remove this DNA coding system, and thus record a step-by-step history of some of the viable genetic events (natural or man-controlled) that have created the organism and the breed. Amino acid sequences can be used to trace the progress of controlled breeding in two ways: by extrapolation back from living breeds, and by analysis of ancient protein material. Of the latter, bone or tendon or skin collagens and hair keratins are the most perfectly preserved as molecular structures through 20,000 years and indeed much longer. Amino acid sequences are expensive to determine (collagen has 1052 amino acid residues), and the potential of this palaeobiological information has been as yet little exploited. The first approach has, however, been more explored, in both plants and animals. Several protein systems must be studied in conjunction to reveal the phylogenetic threads in any one breed. As the three dimensional quaternary structure of protein molecules becomes more appreciated in relation to biological function, and as new techniques and procedures are developed, amino acid sequence data can become more informative in our ultimate understanding of early selective breeding.", "contents": "The evolution of plants and animals under domestication: the contribution of studies at the molecular level. Protein molecules are essential catalysts in life processes and also form much of the substance of living material. Their three dimensional structures determine their biological function. Their biosynthesis is primarily determined by arrays of nucleic acid macromolecules (DNA and RNA), and the amino acid sequences that constitute their long spatially organized peptide-chain molecules reflect at one remove this DNA coding system, and thus record a step-by-step history of some of the viable genetic events (natural or man-controlled) that have created the organism and the breed. Amino acid sequences can be used to trace the progress of controlled breeding in two ways: by extrapolation back from living breeds, and by analysis of ancient protein material. Of the latter, bone or tendon or skin collagens and hair keratins are the most perfectly preserved as molecular structures through 20,000 years and indeed much longer. Amino acid sequences are expensive to determine (collagen has 1052 amino acid residues), and the potential of this palaeobiological information has been as yet little exploited. The first approach has, however, been more explored, in both plants and animals. Several protein systems must be studied in conjunction to reveal the phylogenetic threads in any one breed. As the three dimensional quaternary structure of protein molecules becomes more appreciated in relation to biological function, and as new techniques and procedures are developed, amino acid sequence data can become more informative in our ultimate understanding of early selective breeding."}
{"id": "PMID:11514", "title": "Organization of motoneurones in the prothoracic ganglion of the cockroach Periplaneta americana (L.).", "content": "The location within the prothoracic ganglion of neurone somata with axons in identified peripheral nerves is examined by the cobalt iontophoresis technique. Axons are filled with cobalt by diffusion through their cut ends and the cobalt is then precipitated as the black sulphide inside the neurone. It is assumed that neurones with axons in peripheral nerves and somata in central ganglia are either motor or neuro-secretory. Fifteen nerves are examined and maps of the location of somata with axons in each nerve are presented. The axon distribution in peripheral nerves of three common inhibitory neurones is described. Dendritic morphology of one common inhibitory neurone and two coxal depressor motoneurones is illustrated. It is proposed that some individual neurones can be reliably identified from their soma dimensions and location within the ganglion. The number of motoneurones with somata in the prothoracic ganglion and their homology with cells in the other thoracic ganglia are discussed.", "contents": "Organization of motoneurones in the prothoracic ganglion of the cockroach Periplaneta americana (L.). The location within the prothoracic ganglion of neurone somata with axons in identified peripheral nerves is examined by the cobalt iontophoresis technique. Axons are filled with cobalt by diffusion through their cut ends and the cobalt is then precipitated as the black sulphide inside the neurone. It is assumed that neurones with axons in peripheral nerves and somata in central ganglia are either motor or neuro-secretory. Fifteen nerves are examined and maps of the location of somata with axons in each nerve are presented. The axon distribution in peripheral nerves of three common inhibitory neurones is described. Dendritic morphology of one common inhibitory neurone and two coxal depressor motoneurones is illustrated. It is proposed that some individual neurones can be reliably identified from their soma dimensions and location within the ganglion. The number of motoneurones with somata in the prothoracic ganglion and their homology with cells in the other thoracic ganglia are discussed."}
{"id": "PMID:11518", "title": "[Autogenic training within the therapeutic scope of schizophrenic patients].", "content": "The author calls the reader's attention to the rather strange fact that autogenic training, in spite of worldwide recognition and extensive uses of the method in various disciplines of medicine and spheres of live, has not so far been finding wide application in the medical specialty dealing with mental disorders. After discussing some possible causes of this situation and commenting on first signs of a necessary change in attitude toward autogenic training, he reports his own experience in the treatment of schizophrenic patients with this psychotherapeutic method, emphasizing the need for including psychotherapy in a complex concept of the treatment of psychoses.", "contents": "[Autogenic training within the therapeutic scope of schizophrenic patients]. The author calls the reader's attention to the rather strange fact that autogenic training, in spite of worldwide recognition and extensive uses of the method in various disciplines of medicine and spheres of live, has not so far been finding wide application in the medical specialty dealing with mental disorders. After discussing some possible causes of this situation and commenting on first signs of a necessary change in attitude toward autogenic training, he reports his own experience in the treatment of schizophrenic patients with this psychotherapeutic method, emphasizing the need for including psychotherapy in a complex concept of the treatment of psychoses."}
{"id": "PMID:11519", "title": "Possible association of schizophrenia with a disturbance in prostaglandin metabolism: a physiological hypothesis.", "content": "Schizophrenia may be associated with increased prostaglandin synthesis in certain parts of the brain. This hypothesis is based on the following findings: (1) Catalepsy, which is the nearest equivalent in animals to human catatonia, develops in cats when prostaglandin E1 is injected into the cerebral ventricles and when during endotoxin or lipid A fever the prostaglandin E2 level in cisternal c.s.f. rises to high levels; however, when fever and prostaglandin level are brought down by non-steroid anti-pyretics which inhibit prostaglandin synthesis, catalepsy disappears as well. (2) Febrile episodes are a genuine syndrome of schizophrenia.", "contents": "Possible association of schizophrenia with a disturbance in prostaglandin metabolism: a physiological hypothesis. Schizophrenia may be associated with increased prostaglandin synthesis in certain parts of the brain. This hypothesis is based on the following findings: (1) Catalepsy, which is the nearest equivalent in animals to human catatonia, develops in cats when prostaglandin E1 is injected into the cerebral ventricles and when during endotoxin or lipid A fever the prostaglandin E2 level in cisternal c.s.f. rises to high levels; however, when fever and prostaglandin level are brought down by non-steroid anti-pyretics which inhibit prostaglandin synthesis, catalepsy disappears as well. (2) Febrile episodes are a genuine syndrome of schizophrenia."}
{"id": "PMID:11521", "title": "Ontogenetic development of locomotor activity and rate of tyrosine hydroxylation.", "content": "A combined biochemical and behavioral study was performed postnatally on albino rats. An almost linear increase in total motor activity was observed from 1 to 15 days of age followed by a pronounced decrease in motor activity between days 15 and 18. The in vivo rate of tyrosine hydroxylase activity in whole brain was estimated by means of measuring accumulation of L-3,4-dihydroxyphenylalanine (Dopa) after administration of an inhibitor of aromatic amino acid decarboxylase NSD 1015. Additionally, Dopa accumulation was studied in regional brain areas in 10 and 14-day-old animals. A slight gradual increase in the amount of Dopa accumulation in whole brain was observed from 1 to 10 days of age, followed by a pronounced increase between 10 and 14 days. Regional studies revealed that the increase in Dopa accumulation was primarily located to striatum. The data suggest an involvement of central catecholamine neurons possibly dopaminergic, terminating in striatum. The decrease in motor activity observed after 15 days of age is interpreted as involvement of maturing inhibitory pathways of noncatecholaminergic origin.", "contents": "Ontogenetic development of locomotor activity and rate of tyrosine hydroxylation. A combined biochemical and behavioral study was performed postnatally on albino rats. An almost linear increase in total motor activity was observed from 1 to 15 days of age followed by a pronounced decrease in motor activity between days 15 and 18. The in vivo rate of tyrosine hydroxylase activity in whole brain was estimated by means of measuring accumulation of L-3,4-dihydroxyphenylalanine (Dopa) after administration of an inhibitor of aromatic amino acid decarboxylase NSD 1015. Additionally, Dopa accumulation was studied in regional brain areas in 10 and 14-day-old animals. A slight gradual increase in the amount of Dopa accumulation in whole brain was observed from 1 to 10 days of age, followed by a pronounced increase between 10 and 14 days. Regional studies revealed that the increase in Dopa accumulation was primarily located to striatum. The data suggest an involvement of central catecholamine neurons possibly dopaminergic, terminating in striatum. The decrease in motor activity observed after 15 days of age is interpreted as involvement of maturing inhibitory pathways of noncatecholaminergic origin."}
{"id": "PMID:11523", "title": "In vivo desensitization of a phobic shop steward.", "content": "Techniques used in behaviour therapy effectively counteract the symptoms presented by the patient. The question arises as to the precise nature of such intervention, and whether this form of treatment is in fact a superficial one which deals only with symptom removal, or whether this is really a much more fundamental form of therapy, in which the patient alters as a whole. The case reported here is of interest in that, during a course of in vivo desensitization, in which the therapist accompanied the patient on journeys through London, it was shown that, as the symptoms were alleviated, there were concomitant changes in his whole personality structure. He no longer needed to be a militant shop steward and developed an amicable relationship with his employers, and yet he was still able to negotiate a pay rise for the men. This suggests that the treatment had an effect on his hostility level, so that he could deal effectively with his superiors without the need to fight them. This has important theoretical and ethnical implications.", "contents": "In vivo desensitization of a phobic shop steward. Techniques used in behaviour therapy effectively counteract the symptoms presented by the patient. The question arises as to the precise nature of such intervention, and whether this form of treatment is in fact a superficial one which deals only with symptom removal, or whether this is really a much more fundamental form of therapy, in which the patient alters as a whole. The case reported here is of interest in that, during a course of in vivo desensitization, in which the therapist accompanied the patient on journeys through London, it was shown that, as the symptoms were alleviated, there were concomitant changes in his whole personality structure. He no longer needed to be a militant shop steward and developed an amicable relationship with his employers, and yet he was still able to negotiate a pay rise for the men. This suggests that the treatment had an effect on his hostility level, so that he could deal effectively with his superiors without the need to fight them. This has important theoretical and ethnical implications."}
{"id": "PMID:11526", "title": "Characterization of interactions of phenothiazines and related drugs with lipids by UV-spectrophotometry.", "content": "The UV-spectrum of chlorpromazine undergoes a red shift in the presence of vesicles of biological membranes or phospholipids, triglycerides, serum lipoproteins or fatty acids. The resulting difference spectrum has two positive peaks at about 260 and 320 nm and two negative peaks at 250 and 290 nm. This interaction signal, which was elicited in the presence of as little as 3 muM oleic acid, was dependent on the concentrations of both ligand and binder. It was abolished by 8 M urea, diminished by temperature increase up to 70 degrees C, but not changed by varying the ionic strength from 0 to 0.5. The chlorpromazine-triglyceride interaction signal was strongly enhanced with pH increasing from 6 to 10. The signal was only obtained with ligands fulfilling specific structural requirements, e.g., phenothiazines and most iminostilbenes, but not carbamazepine, imipramine, and amitriptyline.", "contents": "Characterization of interactions of phenothiazines and related drugs with lipids by UV-spectrophotometry. The UV-spectrum of chlorpromazine undergoes a red shift in the presence of vesicles of biological membranes or phospholipids, triglycerides, serum lipoproteins or fatty acids. The resulting difference spectrum has two positive peaks at about 260 and 320 nm and two negative peaks at 250 and 290 nm. This interaction signal, which was elicited in the presence of as little as 3 muM oleic acid, was dependent on the concentrations of both ligand and binder. It was abolished by 8 M urea, diminished by temperature increase up to 70 degrees C, but not changed by varying the ionic strength from 0 to 0.5. The chlorpromazine-triglyceride interaction signal was strongly enhanced with pH increasing from 6 to 10. The signal was only obtained with ligands fulfilling specific structural requirements, e.g., phenothiazines and most iminostilbenes, but not carbamazepine, imipramine, and amitriptyline."}
{"id": "PMID:11528", "title": "Discriminative response control by psychomotor stimulants.", "content": "Psychomotor stimulants are capable of controlling discriminative responding in rats. Evidence suggests that response control is central, of a fairly specific nature, and dependent on intact dopaminergic functions.", "contents": "Discriminative response control by psychomotor stimulants. Psychomotor stimulants are capable of controlling discriminative responding in rats. Evidence suggests that response control is central, of a fairly specific nature, and dependent on intact dopaminergic functions."}
{"id": "PMID:11529", "title": "Discriminable effects of benzodiazepines.", "content": "In a shock-escape T-maze task, rats rapidly discriminated diazepam, flurazepam and chloridazepoxide from no drug. The discriminable effects of these benzodiazepines were not completely interchangeable with those of barbiturate anesthetics. The dose-response curve for diazepam asymptoted over the range 15 to 100 mg/kg, ip whereas dose-response curves for flurazepam and chloridazepoxide were more linear.", "contents": "Discriminable effects of benzodiazepines. In a shock-escape T-maze task, rats rapidly discriminated diazepam, flurazepam and chloridazepoxide from no drug. The discriminable effects of these benzodiazepines were not completely interchangeable with those of barbiturate anesthetics. The dose-response curve for diazepam asymptoted over the range 15 to 100 mg/kg, ip whereas dose-response curves for flurazepam and chloridazepoxide were more linear."}
{"id": "PMID:11531", "title": "Effects of drugs on the uptake of acetylcholine by human term placenta fragments.", "content": "An active concentrative component of the ACh accumulation in fragments of human term placenta followed kinetics predicted by the Michaelis-Menten equation (Km greater than 15 mM). This process was competitively inhibited by choline or hemicholinium-3, suggesting the possibility that a common carrier existed. Morphine reduced the 3 H-ACh uptake competitively. Imipramine, desmethylimipramine, haloperidol and chlorpromazine decreased the concentration ratios. This effect was uncompetitive with respect to chlorpromazine. Compared to drug actions on the ACh uptake in innervated tissue drug effects in the placenta were much less predictable for various classes of compounds.", "contents": "Effects of drugs on the uptake of acetylcholine by human term placenta fragments. An active concentrative component of the ACh accumulation in fragments of human term placenta followed kinetics predicted by the Michaelis-Menten equation (Km greater than 15 mM). This process was competitively inhibited by choline or hemicholinium-3, suggesting the possibility that a common carrier existed. Morphine reduced the 3 H-ACh uptake competitively. Imipramine, desmethylimipramine, haloperidol and chlorpromazine decreased the concentration ratios. This effect was uncompetitive with respect to chlorpromazine. Compared to drug actions on the ACh uptake in innervated tissue drug effects in the placenta were much less predictable for various classes of compounds."}
{"id": "PMID:11545", "title": "Postoperative treatment with corticosteroids and salazosulphapyridine (Salazopyrin) after radical resection for Crohn's disease.", "content": "In a prospective multicentre study, 97 patients with Crohn's disease and operated on by a radical excision of the Crohn-involved bowel were randomly divided into two groups, one treated 33 weeks postoperatively by corticosteroids and Salazopyrin and the other without any medical treatment postoperatively. The patients in the two groups were followed up during three years after the operation and an X-ray of the bowel was yearly performed. Thirteen patients were excluded for different reasons, which means that 84 patients were left for the study. There was no statistically significant difference in the number of recurrences after one, two, or three years of observation time in the two groups of patients. There was a statistically significantly longer time between diagnosis and operation in the group of patients with recurrences than in patients with no recurrences. This might mean that patients with Crohn's disease undergoing an early operation have a better chance of escaping recurrences.", "contents": "Postoperative treatment with corticosteroids and salazosulphapyridine (Salazopyrin) after radical resection for Crohn's disease. In a prospective multicentre study, 97 patients with Crohn's disease and operated on by a radical excision of the Crohn-involved bowel were randomly divided into two groups, one treated 33 weeks postoperatively by corticosteroids and Salazopyrin and the other without any medical treatment postoperatively. The patients in the two groups were followed up during three years after the operation and an X-ray of the bowel was yearly performed. Thirteen patients were excluded for different reasons, which means that 84 patients were left for the study. There was no statistically significant difference in the number of recurrences after one, two, or three years of observation time in the two groups of patients. There was a statistically significantly longer time between diagnosis and operation in the group of patients with recurrences than in patients with no recurrences. This might mean that patients with Crohn's disease undergoing an early operation have a better chance of escaping recurrences."}
{"id": "PMID:11546", "title": "Endogenous motilin and the LES pressure.", "content": "The changes in LES pressure were measured after alkalinization and subsequent acidification of the antrum or duodenum. For the alkalinization of the antrum, a strong (sodium-hydroxide) and a weaker alkaline stimulus were used in different subjects. At the end of the experiments, glycine 5% was infused into antrum and glycine 5% or phenylalanine 0.1 N into the duodenum. Plasma samples were drawn for determination of the motilin levels. Although in some experimental situations, motilin levels and LES pressure were significantly correlated, any correlation was lacking in other test situations. It may be concluded that the role of endogenous motilin for the regulation of the LES pressure is either non-existent or frequently overwhelmed by other influences.", "contents": "Endogenous motilin and the LES pressure. The changes in LES pressure were measured after alkalinization and subsequent acidification of the antrum or duodenum. For the alkalinization of the antrum, a strong (sodium-hydroxide) and a weaker alkaline stimulus were used in different subjects. At the end of the experiments, glycine 5% was infused into antrum and glycine 5% or phenylalanine 0.1 N into the duodenum. Plasma samples were drawn for determination of the motilin levels. Although in some experimental situations, motilin levels and LES pressure were significantly correlated, any correlation was lacking in other test situations. It may be concluded that the role of endogenous motilin for the regulation of the LES pressure is either non-existent or frequently overwhelmed by other influences."}
{"id": "PMID:11547", "title": "Relationship of plasma motilin response to lower esophageal sphincter pressure in man.", "content": "The effect of intraduodenal instillation of 0.1 N hydrochloric acid or 0.9% saline (control) on lower esophageal sphincter pressure (LESP) and plasma motilin concentrations was studied in five normal volunteers. After acid, LESP and plasma motilin rose concomitantly exceeding basal by about 80% (p less than 0.025) and 90% (p less than 0.05), respectively, at 3 to 4 minutes. Control values did not significantly differ throughout the test period from the mean basal level. These results are compatible with the view that the increase in LESP after duodenal acidification may be mediated by endogenously released motilin.", "contents": "Relationship of plasma motilin response to lower esophageal sphincter pressure in man. The effect of intraduodenal instillation of 0.1 N hydrochloric acid or 0.9% saline (control) on lower esophageal sphincter pressure (LESP) and plasma motilin concentrations was studied in five normal volunteers. After acid, LESP and plasma motilin rose concomitantly exceeding basal by about 80% (p less than 0.025) and 90% (p less than 0.05), respectively, at 3 to 4 minutes. Control values did not significantly differ throughout the test period from the mean basal level. These results are compatible with the view that the increase in LESP after duodenal acidification may be mediated by endogenously released motilin."}
{"id": "PMID:11548", "title": "Fetal thymus transplantations in severe combined immunodeficiency.", "content": "Two brothers with severe combined immunodeficiency were treated with repeated transplantations of fetal thymus tissue. The first patient was not treated until he was critically ill, and the intramuscular transplants had no effect. He died at 11 months of age of overwhelming pneumonia. At postmortem examination a transplanted thymus seemed viable. In the second patient an intramuscular transplant had no effect, but three subsequent intraperitoneal transplants led to transient increase in circulating T lymphocytes with a concomitant fall in B lymphocytes. The results suggested an additive effect of each transplant. However, delayed hypersensitivity skin tests and in vitro mitogen responses were not influenced. Initially, transfer factor was given, and fetal liver was administered intraperitoneally together with the last thymic transplant. Neither of these measures had any observed effect, and this patient, similarly, died of pneumonia at nearly 12 months of age.", "contents": "Fetal thymus transplantations in severe combined immunodeficiency. Two brothers with severe combined immunodeficiency were treated with repeated transplantations of fetal thymus tissue. The first patient was not treated until he was critically ill, and the intramuscular transplants had no effect. He died at 11 months of age of overwhelming pneumonia. At postmortem examination a transplanted thymus seemed viable. In the second patient an intramuscular transplant had no effect, but three subsequent intraperitoneal transplants led to transient increase in circulating T lymphocytes with a concomitant fall in B lymphocytes. The results suggested an additive effect of each transplant. However, delayed hypersensitivity skin tests and in vitro mitogen responses were not influenced. Initially, transfer factor was given, and fetal liver was administered intraperitoneally together with the last thymic transplant. Neither of these measures had any observed effect, and this patient, similarly, died of pneumonia at nearly 12 months of age."}
{"id": "PMID:11549", "title": "Partial tolerant state against H-2 disparate cells. No impaired specific reactivity in MLC, GVH, or antibody production.", "content": "Injection of CBA mice with H-2-compatible lymphoid cells from C3H hybrids induces a specific reduction of the mixed lymphocyte culture (MLC) response of their lymphoytes. This is not the case after injection of H-2-disparate C3H-hybrid cells, presumably because they are rapidly eliminated due to the immune response of the host. This investigation shows that CBA mice injected with CBA X C57Bl cells (H-2-disparate) at an age of 0-3 days, but not older, develop a specifically reduced MLC response after infusion of C3H X C57Bl cells as adults, indicating that they were tolerant to the C57Bl-determined antigens. However, lymphocytes from such mice showed a normal reactivity against C57Bl as assessed by MLC, graft-versus-host tests, and capacity to produce specific antibodies.", "contents": "Partial tolerant state against H-2 disparate cells. No impaired specific reactivity in MLC, GVH, or antibody production. Injection of CBA mice with H-2-compatible lymphoid cells from C3H hybrids induces a specific reduction of the mixed lymphocyte culture (MLC) response of their lymphoytes. This is not the case after injection of H-2-disparate C3H-hybrid cells, presumably because they are rapidly eliminated due to the immune response of the host. This investigation shows that CBA mice injected with CBA X C57Bl cells (H-2-disparate) at an age of 0-3 days, but not older, develop a specifically reduced MLC response after infusion of C3H X C57Bl cells as adults, indicating that they were tolerant to the C57Bl-determined antigens. However, lymphocytes from such mice showed a normal reactivity against C57Bl as assessed by MLC, graft-versus-host tests, and capacity to produce specific antibodies."}
{"id": "PMID:11550", "title": "Renal function in experimental chronic hydronephrosis. V. Net acid excretion capacity in relation to renal pelvic volume after maximal loading with NH4Cl.", "content": "In 12 mongrel dogs intravenous loading with ammonium chloride (4 mmol NH4+/kg body weight) was performed before and 2-9 weeks after unilateral hydronephrosis had been produced by ligation of the ureter over an indwelling catheter. In an attempt to satisfy the demand for adequate, constant, alveolar ventilation a special respirator of the high-frequency positive-pressure ventilation (HFPPV) type was used. The acid-base status of the blood was determined before and after the loading and the acidification capacity of each kidney was assessed by measuring the amount of titratable acid and ammonium ions excreted in the urine. In the hydronephrotic kidney the excretion of both titratable acid and ammonium ions was statistically significantly reduced, both compared with the initial values in session I and compared with the healthy kidney in session II. After additional loading with ammonium chloride in session II, however, both kidneys increased their excretions to approximately similar extents. When the excretion was calculated per ml glomerular filtrate, no statistically significant changes were found between sessions I and II, either for the intact or the hydronephrotic kidney. The renal pelvic volume on the hydronephrotic side was measured and related to the reduction of the capacity of the kidney to excrete titratable acid and ammonium ions. No statistically significant correlation was obtained.", "contents": "Renal function in experimental chronic hydronephrosis. V. Net acid excretion capacity in relation to renal pelvic volume after maximal loading with NH4Cl. In 12 mongrel dogs intravenous loading with ammonium chloride (4 mmol NH4+/kg body weight) was performed before and 2-9 weeks after unilateral hydronephrosis had been produced by ligation of the ureter over an indwelling catheter. In an attempt to satisfy the demand for adequate, constant, alveolar ventilation a special respirator of the high-frequency positive-pressure ventilation (HFPPV) type was used. The acid-base status of the blood was determined before and after the loading and the acidification capacity of each kidney was assessed by measuring the amount of titratable acid and ammonium ions excreted in the urine. In the hydronephrotic kidney the excretion of both titratable acid and ammonium ions was statistically significantly reduced, both compared with the initial values in session I and compared with the healthy kidney in session II. After additional loading with ammonium chloride in session II, however, both kidneys increased their excretions to approximately similar extents. When the excretion was calculated per ml glomerular filtrate, no statistically significant changes were found between sessions I and II, either for the intact or the hydronephrotic kidney. The renal pelvic volume on the hydronephrotic side was measured and related to the reduction of the capacity of the kidney to excrete titratable acid and ammonium ions. No statistically significant correlation was obtained."}
{"id": "PMID:11552", "title": "[Graft versus host disease, a little known complication of blood transfusion].", "content": "A case of fatal graft-versus-host disease (GvHD) following blood transfusions is reported. This relatively rare complication of blood and bloodcomponent replacement therapy may occur in recipients with decreased cellular immunity, which may be due to the underlying disease, chemotherapy or radiation therapy, or a combination of both. GvHD is a result of active proliferation of transfused immunologically competent cells which attack host organs. This complication can be prevented by irradiating transfusions with 1500 rads in vitro.", "contents": "[Graft versus host disease, a little known complication of blood transfusion]. A case of fatal graft-versus-host disease (GvHD) following blood transfusions is reported. This relatively rare complication of blood and bloodcomponent replacement therapy may occur in recipients with decreased cellular immunity, which may be due to the underlying disease, chemotherapy or radiation therapy, or a combination of both. GvHD is a result of active proliferation of transfused immunologically competent cells which attack host organs. This complication can be prevented by irradiating transfusions with 1500 rads in vitro."}
{"id": "PMID:11553", "title": "[Glucagon producing adenomatosis of Islands of Langerhans with polyendocrine symptoms].", "content": "A patient in whom Cushing syndrome had been diagnosed at the age of 23 was found 14 years later to have subclinical diabetes mellitus, subcutaneous calcified fat tissue necroses, and hypergastrinemia suggesting Zollinger-Ellison syndrome. Histopathologic investigation revealed pancreatic adenomatosis of the glucagon producing A2-cells with accompanying B-cell hyperplasia, and hyperplasia of the adrenal cortex. The origin of the increased serum gastrin concentration in this patient is not yet known. The significance of A2-cell proliferation in Zollinger-Ellison syndrome and and in multiple endocrine adenomatosis is discussed.", "contents": "[Glucagon producing adenomatosis of Islands of Langerhans with polyendocrine symptoms]. A patient in whom Cushing syndrome had been diagnosed at the age of 23 was found 14 years later to have subclinical diabetes mellitus, subcutaneous calcified fat tissue necroses, and hypergastrinemia suggesting Zollinger-Ellison syndrome. Histopathologic investigation revealed pancreatic adenomatosis of the glucagon producing A2-cells with accompanying B-cell hyperplasia, and hyperplasia of the adrenal cortex. The origin of the increased serum gastrin concentration in this patient is not yet known. The significance of A2-cell proliferation in Zollinger-Ellison syndrome and and in multiple endocrine adenomatosis is discussed."}
{"id": "PMID:11554", "title": "[Diphenylhydantoin. Metabolism, pharmacokinetics, interactions and side effects].", "content": "The metabolism, mechanism of action, interactions with other drugs and side effects of diphenylhydantoin (DPH), which is probably the most commonly used antiepileptic drug are reviewed in the light of the recent literature. Some findings of practical importance are emphasized, and the resultant implications with regard to the management of epileptic patients are discussed.", "contents": "[Diphenylhydantoin. Metabolism, pharmacokinetics, interactions and side effects]. The metabolism, mechanism of action, interactions with other drugs and side effects of diphenylhydantoin (DPH), which is probably the most commonly used antiepileptic drug are reviewed in the light of the recent literature. Some findings of practical importance are emphasized, and the resultant implications with regard to the management of epileptic patients are discussed."}
{"id": "PMID:11555", "title": "[The petit-mal-status].", "content": "In the light of three case histories, other personal observations and the literature, the clinical and electroencephalographical differences between absences in the limited sense and continuous LENNOX petit-mal state are described and the problems of the latter discussed. As a rule, petit-mal state is diagnosed as such in young people or adults, and practically never before the 10th year of life. In about two thirds of cases, its clinical symptomatology consists of a twilight condition lasting some hours to a few days, coupled with inertia and apathy. The remaining third of the patients usually experience milder disturbances, e.g. in the form of concentration difficulties, tiredness, and (more rarely) severe forms including lethargy. The EEG correlate of a petit-mal state is made up of continuous bilaterally synchronous, frontally marked (less frequently with exclusively frontal localization), usually irregular spike waves or poly-spike waves, which frequently occur in only rudimentary forms and register a frequency of 2 1/2-4 c/sec. For the treatment of petit-mal state, benzodiazepines and in particular clonazepam (Rivotril) (1-2 mg i.v.) are recommended. During the interval condition the same therapy as with an absence epilepsy, e.g. succinimides or dipropylacetate (Depakine) is administered. Anti-grand-mal remedies, especially hydantoins, may trigger petit-mal status.", "contents": "[The petit-mal-status]. In the light of three case histories, other personal observations and the literature, the clinical and electroencephalographical differences between absences in the limited sense and continuous LENNOX petit-mal state are described and the problems of the latter discussed. As a rule, petit-mal state is diagnosed as such in young people or adults, and practically never before the 10th year of life. In about two thirds of cases, its clinical symptomatology consists of a twilight condition lasting some hours to a few days, coupled with inertia and apathy. The remaining third of the patients usually experience milder disturbances, e.g. in the form of concentration difficulties, tiredness, and (more rarely) severe forms including lethargy. The EEG correlate of a petit-mal state is made up of continuous bilaterally synchronous, frontally marked (less frequently with exclusively frontal localization), usually irregular spike waves or poly-spike waves, which frequently occur in only rudimentary forms and register a frequency of 2 1/2-4 c/sec. For the treatment of petit-mal state, benzodiazepines and in particular clonazepam (Rivotril) (1-2 mg i.v.) are recommended. During the interval condition the same therapy as with an absence epilepsy, e.g. succinimides or dipropylacetate (Depakine) is administered. Anti-grand-mal remedies, especially hydantoins, may trigger petit-mal status."}
{"id": "PMID:11556", "title": "[The behavior of gamma-glutamyltranspeptidase and other liver enzymes in the plasma during alcohol withdrawal treatments].", "content": "90 chronic alcoholics (55 men and 35 women, aged between 20 and 60 years) were investigated to determine how alcohol withdrawal effects the pattern of enzymes in plasma and if changes in this enzyme pattern could be used as criteria for evaluation of the recovery process. Among the different enzymes tested, gamma-glutamyl-transpeptidase (GGTP) and the transamines seemed the most suitable parameters. At the beginning of the alcohol withdrawal course, 79 out of 90 patients (80%) showed elevated values of one of these enzymes in plasma. GOT was elevated in 31 (34%), GPT in 24 (23%) and GGTP in 79 (88%) of the cases. In 49 patients (54%) GGTP was the only enzyme found to be elevated. The values of GGTP were on the average higher than those of GOT and GPT. GGTP has thereforeto be regarded as the most sensitive enzyme since it was elevated in most of the patients. GGTP reacted with 6.8 times more sensitivity than GOT and 6.3 times that of GPT. After withdrawal of alcohol the three enzymes showed a decline in all 79 patients. The transaminases normalized faster than GGTP. GTP fell into the upper normal limit after only 30 days. Among the 90 alcoholics examined, 14 relapsed during the alcohol withdrawal course. After the new excess of alcohol intake, the GGTP in plasma rose immediately. Alcohol abuse was suspected in 50% of the patients due to the increase in this enzyme and was subsequently confirmed by the patients. Acute alcohol loading in normal volunteers did not lead to an increase in GGTP activity. A comparison of the histology of liver biopsy material showed that neither the transaminases nor the alkaline phosphatase and GGTP served to differentiate the various forms of alcoholic liver damage. However, GGTP represents the most sensitive enzymatic parameter for the detection of alcoholic liver disease. This enzyme is useful in evaluating the success of a course of alcohol deprivation. The decreasing values during such treatment, as well as the prompt increase after a relapse, points to the high sensitivity of this enzyme. A further argument is that in 54% of the patients elevation of GGTP only was present. Since no liver damage could be demonstrated in these patients with the aid of the other liver enzymes, the elevation of GGTP may be related to the alcohol intake through an enzyme induction mechanism such as has been demonstrated for this enzyme with certain drugs.", "contents": "[The behavior of gamma-glutamyltranspeptidase and other liver enzymes in the plasma during alcohol withdrawal treatments]. 90 chronic alcoholics (55 men and 35 women, aged between 20 and 60 years) were investigated to determine how alcohol withdrawal effects the pattern of enzymes in plasma and if changes in this enzyme pattern could be used as criteria for evaluation of the recovery process. Among the different enzymes tested, gamma-glutamyl-transpeptidase (GGTP) and the transamines seemed the most suitable parameters. At the beginning of the alcohol withdrawal course, 79 out of 90 patients (80%) showed elevated values of one of these enzymes in plasma. GOT was elevated in 31 (34%), GPT in 24 (23%) and GGTP in 79 (88%) of the cases. In 49 patients (54%) GGTP was the only enzyme found to be elevated. The values of GGTP were on the average higher than those of GOT and GPT. GGTP has thereforeto be regarded as the most sensitive enzyme since it was elevated in most of the patients. GGTP reacted with 6.8 times more sensitivity than GOT and 6.3 times that of GPT. After withdrawal of alcohol the three enzymes showed a decline in all 79 patients. The transaminases normalized faster than GGTP. GTP fell into the upper normal limit after only 30 days. Among the 90 alcoholics examined, 14 relapsed during the alcohol withdrawal course. After the new excess of alcohol intake, the GGTP in plasma rose immediately. Alcohol abuse was suspected in 50% of the patients due to the increase in this enzyme and was subsequently confirmed by the patients. Acute alcohol loading in normal volunteers did not lead to an increase in GGTP activity. A comparison of the histology of liver biopsy material showed that neither the transaminases nor the alkaline phosphatase and GGTP served to differentiate the various forms of alcoholic liver damage. However, GGTP represents the most sensitive enzymatic parameter for the detection of alcoholic liver disease. This enzyme is useful in evaluating the success of a course of alcohol deprivation. The decreasing values during such treatment, as well as the prompt increase after a relapse, points to the high sensitivity of this enzyme. A further argument is that in 54% of the patients elevation of GGTP only was present. Since no liver damage could be demonstrated in these patients with the aid of the other liver enzymes, the elevation of GGTP may be related to the alcohol intake through an enzyme induction mechanism such as has been demonstrated for this enzyme with certain drugs."}
{"id": "PMID:11557", "title": "[Impotence and male sterility].", "content": "The causes of sexual impotence, including disturbances of ejaculation, and the methods of treatment are described. In the vast majority of cases male sterility results from a disorder of spermatogenesis. The main factors responsible for infertile semen are discussed: in most cases the causes are unknown. It is to be hoped that progress in research into human reproduction and recent diagnostic advances will provide the groundwork for more successful therapy of male sterility.", "contents": "[Impotence and male sterility]. The causes of sexual impotence, including disturbances of ejaculation, and the methods of treatment are described. In the vast majority of cases male sterility results from a disorder of spermatogenesis. The main factors responsible for infertile semen are discussed: in most cases the causes are unknown. It is to be hoped that progress in research into human reproduction and recent diagnostic advances will provide the groundwork for more successful therapy of male sterility."}
{"id": "PMID:11560", "title": "Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia.", "content": "Sensitization is an elementary form of nonassociative learning, related to behavioral arousal, in which a strong stimulus facilitates a reflex response. Studies of the neural circuit of the gill-withdrawal reflex in the isolated abdominal ganglion on Aplysia indicate that short-term sensitization is due to presynaptic facilitation. The facilitation results in a sudden increase in the amount of neurotransmitter released by the sensory neurons at their synapses with motor neurons.", "contents": "Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia. Sensitization is an elementary form of nonassociative learning, related to behavioral arousal, in which a strong stimulus facilitates a reflex response. Studies of the neural circuit of the gill-withdrawal reflex in the isolated abdominal ganglion on Aplysia indicate that short-term sensitization is due to presynaptic facilitation. The facilitation results in a sudden increase in the amount of neurotransmitter released by the sensory neurons at their synapses with motor neurons."}
{"id": "PMID:11561", "title": "Recent studies on the identification of proliferative abnormalities and of oncogenic potential of cutaneous cells in individuals at increased risk of colon cancer.", "content": "This recent study describes the growth characteristics of ACR skin fibroblasts in culture and their differential susceptibility to transformation by Kirsten murine sarcoma virus (Ki-MSV). The SF were derived from normal appearing subepidermoid biopsies of ACR individuals, their progeny and ocntrols. Normal SF were contact-inhibited and grew only in 15% FCS. SF of ACR subjects, and some asymptomatic ACR progeny were not contact inhibited, grew in both 1% and 15% FCS and were considerably more susceptible to transformation by Ki-MSV than were control SF. The virally transformed SF showed a loss of anchorage dependency in methylcellulose and formed tumors in athymic mice. The results suggest the presence of early and previously undetected metabolic lesions in SF from clinically asymptomatic subjects. These phenotype markers are currently evaluated for their utility in the clinical diagnosis of individuals with latent ACR and those at increased risk for colon cancer. SF from ACR individuals have been recently shown to contain significant alterations in the intracellular distribution of actin (R. Pollack and L. Kopelovich, in preparation), and elevated levels of plasminogen activator (L. Kopelovich).", "contents": "Recent studies on the identification of proliferative abnormalities and of oncogenic potential of cutaneous cells in individuals at increased risk of colon cancer. This recent study describes the growth characteristics of ACR skin fibroblasts in culture and their differential susceptibility to transformation by Kirsten murine sarcoma virus (Ki-MSV). The SF were derived from normal appearing subepidermoid biopsies of ACR individuals, their progeny and ocntrols. Normal SF were contact-inhibited and grew only in 15% FCS. SF of ACR subjects, and some asymptomatic ACR progeny were not contact inhibited, grew in both 1% and 15% FCS and were considerably more susceptible to transformation by Ki-MSV than were control SF. The virally transformed SF showed a loss of anchorage dependency in methylcellulose and formed tumors in athymic mice. The results suggest the presence of early and previously undetected metabolic lesions in SF from clinically asymptomatic subjects. These phenotype markers are currently evaluated for their utility in the clinical diagnosis of individuals with latent ACR and those at increased risk for colon cancer. SF from ACR individuals have been recently shown to contain significant alterations in the intracellular distribution of actin (R. Pollack and L. Kopelovich, in preparation), and elevated levels of plasminogen activator (L. Kopelovich)."}
{"id": "PMID:11564", "title": "Histamine H2-receptor antagonists in the treatment of duodenal ulcers.", "content": "A double-blind trial of histamine H2-receptor antagonists and placebo was carried out in 46 patients with endoscopically proven duodenal ulceration. H2-receptor antagonists (metiamide and cimetidine) produced a significantly greater degree of completely healed ulcers and fewer complete failures than placebo. The results of the trial indicate that H2-receptor antagonists promote the healing of ulcers. The action of these compounds would appear to be related to the inhibition of acid secretion. Neither the duration of the illness, rate of recurrence of the ulcers of level of gastric acid secretion materially affected the healing rate in indvidual patients. There were no serious side-effects over the 6-week period of drug administration, but the metiamide was replaced by cimetidine because reports from other centrea indicated that agranulocytosis was associtated with metiamide therapy.", "contents": "Histamine H2-receptor antagonists in the treatment of duodenal ulcers. A double-blind trial of histamine H2-receptor antagonists and placebo was carried out in 46 patients with endoscopically proven duodenal ulceration. H2-receptor antagonists (metiamide and cimetidine) produced a significantly greater degree of completely healed ulcers and fewer complete failures than placebo. The results of the trial indicate that H2-receptor antagonists promote the healing of ulcers. The action of these compounds would appear to be related to the inhibition of acid secretion. Neither the duration of the illness, rate of recurrence of the ulcers of level of gastric acid secretion materially affected the healing rate in indvidual patients. There were no serious side-effects over the 6-week period of drug administration, but the metiamide was replaced by cimetidine because reports from other centrea indicated that agranulocytosis was associtated with metiamide therapy."}
{"id": "PMID:11565", "title": "Facts, anecdotes, and new horizons in the medical treatment of duodenal ulcers.", "content": "There continue to be marked differences of opinion regarding how to manage duodenal ulcer disease. Recent developments in medical management which appear of major importance include the development of antagonists of H2-receptors of histamine, the prostaglandins, and transendoscopic instrumentation. Intractability of duodenal ulcer continues to be an over-used category which disguises situations that are easily remedied. Until we have more long-term and complete evaluations of ulcer treatment, we will continue to base therapy on anecdotes and incomplete data.", "contents": "Facts, anecdotes, and new horizons in the medical treatment of duodenal ulcers. There continue to be marked differences of opinion regarding how to manage duodenal ulcer disease. Recent developments in medical management which appear of major importance include the development of antagonists of H2-receptors of histamine, the prostaglandins, and transendoscopic instrumentation. Intractability of duodenal ulcer continues to be an over-used category which disguises situations that are easily remedied. Until we have more long-term and complete evaluations of ulcer treatment, we will continue to base therapy on anecdotes and incomplete data."}
{"id": "PMID:11568", "title": "Factors influencing the ionization of calcium during major surgical procedures.", "content": "The existence of a clinically feasible calcium electrode makes it possible to obtain rapid, accurate levels of ionized calcium. It is now possible to study the actual ionization of calcium under normal and abnormal physiologic conditions. The present investigation was directed at changes in ionized calcium during major surgical procedures. The total series of 125 patients was divided into three groups according to the type of plasma volume expander: group 1, whole blood alone; group 2, whole blood plus exogenous albumin, and group 3, albumin alone. Ionized calcium levels dropped significantly, p less than 0.001, in all three groups. Although albumin alone produced a decrease in ionized calcium, the addition of albumin to whole blood did not result in a greater decline than that experienced with whole blood alone. Chelation with the citrate ion of bank blood preservative was the major factor responsible for the decrease in ionized calcium. There was no statistically significant relationship between the extent of the decrease, the total volume of blood, the volume of blood per kilogram of the rate of transfusion in milliliters per kilogram per minute. Although the ionized calcium level fell initially, it increased while blood administration continued. In view of these facts, it is difficult to estimate the acutal level of ionized calcium at any point during the operation. Twenty patients in the series had ionized calcium levels below 1.25 milliequivalents per liter, range of 0.51 to 1.24 milliequivalents per liter. With the possible exception of one patient, no adverse cardiovascular effects could be attributed to the low levels of ionized calcium. The results in this series confirm our previous conclusion that the administration of exogenous calcium is not necessary during massive transfusion, with the possible exception of bypass open heart procedures and exchange transfusions in children.", "contents": "Factors influencing the ionization of calcium during major surgical procedures. The existence of a clinically feasible calcium electrode makes it possible to obtain rapid, accurate levels of ionized calcium. It is now possible to study the actual ionization of calcium under normal and abnormal physiologic conditions. The present investigation was directed at changes in ionized calcium during major surgical procedures. The total series of 125 patients was divided into three groups according to the type of plasma volume expander: group 1, whole blood alone; group 2, whole blood plus exogenous albumin, and group 3, albumin alone. Ionized calcium levels dropped significantly, p less than 0.001, in all three groups. Although albumin alone produced a decrease in ionized calcium, the addition of albumin to whole blood did not result in a greater decline than that experienced with whole blood alone. Chelation with the citrate ion of bank blood preservative was the major factor responsible for the decrease in ionized calcium. There was no statistically significant relationship between the extent of the decrease, the total volume of blood, the volume of blood per kilogram of the rate of transfusion in milliliters per kilogram per minute. Although the ionized calcium level fell initially, it increased while blood administration continued. In view of these facts, it is difficult to estimate the acutal level of ionized calcium at any point during the operation. Twenty patients in the series had ionized calcium levels below 1.25 milliequivalents per liter, range of 0.51 to 1.24 milliequivalents per liter. With the possible exception of one patient, no adverse cardiovascular effects could be attributed to the low levels of ionized calcium. The results in this series confirm our previous conclusion that the administration of exogenous calcium is not necessary during massive transfusion, with the possible exception of bypass open heart procedures and exchange transfusions in children."}
{"id": "PMID:11571", "title": "Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide.", "content": "Ventilatory response to CO2 was measured before and after two different benzodiazepine hypnotics in both chronic bronchitics and patients without chest disease. Flurazepam, but not nitrazepam, produced a significant decrease in CO2 sensitivity, although there was no significant change in FEV1 or mixed venous PCO2. This is the first unequivocal evidence of central depression of respiration by a benzodiazepine and may be the mechanism by which benzodiazepines cause deterioration in patients with respiratory failure.", "contents": "Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide. Ventilatory response to CO2 was measured before and after two different benzodiazepine hypnotics in both chronic bronchitics and patients without chest disease. Flurazepam, but not nitrazepam, produced a significant decrease in CO2 sensitivity, although there was no significant change in FEV1 or mixed venous PCO2. This is the first unequivocal evidence of central depression of respiration by a benzodiazepine and may be the mechanism by which benzodiazepines cause deterioration in patients with respiratory failure."}
{"id": "PMID:11573", "title": "Comparative studies of the effects of cyclic AMP, various hormones and chloramphenicol on the induction of delta-aminolevulinic acid synthetase and tyrosine aminotransferase in the organ-cultured chick embryo liver.", "content": "Induction of delta-aminolevulinic acid synthetase by allylisopropylacetamide in organ-cultured chick embryo liver was not appreciably influenced by any of cycli AMP, dibutyryl cyclic AMP, theophylline, glucose, insulin, glucagon, epinephrine, isoproterenol, and hydrocortisone, whereas the activity of tyrosine aminotransferase significantly increased in response to cyclic AMP and some of those hormones. Accumulation of delta-aminolevulinic acid synthetase in the cultured liver cytosol fraction was not appreciably increased by the addition of dibutyryl cyclic AMP or insulin to the incubation medium. Apparently the behaviors of the induction of delta-aminolevulinic acid synthetase in chick embryo liver in ovo and in vitro differ from those in the livers of adult chicken and rat. High concentrations of chloramphenicol suppressed significantly the allylisopropylacetamide-induced increase of delta-aminolevulinic acid synthetase as well as incorporation of 14C-leucine into proteins. The activity of tyrosine aminotransferase, however, was rather increased when relatively low concentrations of chloramphenicol were added to the medium.", "contents": "Comparative studies of the effects of cyclic AMP, various hormones and chloramphenicol on the induction of delta-aminolevulinic acid synthetase and tyrosine aminotransferase in the organ-cultured chick embryo liver. Induction of delta-aminolevulinic acid synthetase by allylisopropylacetamide in organ-cultured chick embryo liver was not appreciably influenced by any of cycli AMP, dibutyryl cyclic AMP, theophylline, glucose, insulin, glucagon, epinephrine, isoproterenol, and hydrocortisone, whereas the activity of tyrosine aminotransferase significantly increased in response to cyclic AMP and some of those hormones. Accumulation of delta-aminolevulinic acid synthetase in the cultured liver cytosol fraction was not appreciably increased by the addition of dibutyryl cyclic AMP or insulin to the incubation medium. Apparently the behaviors of the induction of delta-aminolevulinic acid synthetase in chick embryo liver in ovo and in vitro differ from those in the livers of adult chicken and rat. High concentrations of chloramphenicol suppressed significantly the allylisopropylacetamide-induced increase of delta-aminolevulinic acid synthetase as well as incorporation of 14C-leucine into proteins. The activity of tyrosine aminotransferase, however, was rather increased when relatively low concentrations of chloramphenicol were added to the medium."}
{"id": "PMID:11578", "title": "Cytotoxicity in graft-versus-host reaction. II. Lysis of target cells of parental genotyppe by F1 hybrid macrophages.", "content": "Graft-versus-host (GVH) reactions were induced in adult F1 hybrid mice with the i.p. injection of parental strain spleen cells. Peritoneal exudate and spleen cells of the F1 hybrids taken 8 days after the induction of GVH reaction had a nonspecific in vitro cytotoxic effect which was measured by using 51Cr-labeled target cells of parental genotype. The cytotoxic cells in the peritoneal exudates were shown to be macrophages which adhered to plastic surfaces and were sensitive to the toxic action of crystalline silica particles. Moreover, the injection of partially purified syngeneic macrophages into the F1 hybrids undergoing GVH reactions increased the cytotoxic activity of the peritoneal exudate cells obtained from these animals. These results suggest that during GVH reaction host macrophages are activated into a state of nonspecific cytotoxicity.", "contents": "Cytotoxicity in graft-versus-host reaction. II. Lysis of target cells of parental genotyppe by F1 hybrid macrophages. Graft-versus-host (GVH) reactions were induced in adult F1 hybrid mice with the i.p. injection of parental strain spleen cells. Peritoneal exudate and spleen cells of the F1 hybrids taken 8 days after the induction of GVH reaction had a nonspecific in vitro cytotoxic effect which was measured by using 51Cr-labeled target cells of parental genotype. The cytotoxic cells in the peritoneal exudates were shown to be macrophages which adhered to plastic surfaces and were sensitive to the toxic action of crystalline silica particles. Moreover, the injection of partially purified syngeneic macrophages into the F1 hybrids undergoing GVH reactions increased the cytotoxic activity of the peritoneal exudate cells obtained from these animals. These results suggest that during GVH reaction host macrophages are activated into a state of nonspecific cytotoxicity."}
{"id": "PMID:11579", "title": "Cellular and humoral immunity after allogeneic renal transplantation in the rat. V. Appearance of anti-idiotypic antibody and its relationship to cellular immunity after treatment with donor spleen cells and alloantibody.", "content": "Enhancement of LBN F1 renal allograft survival in Lewis (L) rats is achieved by injecting the recipient i.v. with donor antigen (LBN F1 spleen cells) 1 day before transplantation and antidonor antibody (L anti-BN alloantiserum) at the time of transplantation. Treatment with this combination of antigen and antibody also induces the recipient to make L anti-(L anti-BN) anti-idiotypic antibody that reaches peak titers within 10 days. The degree of graft enhancement achieved was increased greatly by delaying transplantation until the peak of the anti-idiotypic antibody response 10 days after treatment with antigen and antibody. Two in vitro assays for cellular immunity (51Cr release and microcytotoxicity) failed to demonstrate antidonor activity in spleen cells from recipients for which transplantation had been delayed 10 days. The close correlation of enhancement, absence of cellular immunity in vitro, and the kinetics of the anti-idiotypic antibody response suggest that anti-idiotypic antibody may prevent either sensitization and generation of effector T lymphocytes or the destructive potential of sensitized cells.", "contents": "Cellular and humoral immunity after allogeneic renal transplantation in the rat. V. Appearance of anti-idiotypic antibody and its relationship to cellular immunity after treatment with donor spleen cells and alloantibody. Enhancement of LBN F1 renal allograft survival in Lewis (L) rats is achieved by injecting the recipient i.v. with donor antigen (LBN F1 spleen cells) 1 day before transplantation and antidonor antibody (L anti-BN alloantiserum) at the time of transplantation. Treatment with this combination of antigen and antibody also induces the recipient to make L anti-(L anti-BN) anti-idiotypic antibody that reaches peak titers within 10 days. The degree of graft enhancement achieved was increased greatly by delaying transplantation until the peak of the anti-idiotypic antibody response 10 days after treatment with antigen and antibody. Two in vitro assays for cellular immunity (51Cr release and microcytotoxicity) failed to demonstrate antidonor activity in spleen cells from recipients for which transplantation had been delayed 10 days. The close correlation of enhancement, absence of cellular immunity in vitro, and the kinetics of the anti-idiotypic antibody response suggest that anti-idiotypic antibody may prevent either sensitization and generation of effector T lymphocytes or the destructive potential of sensitized cells."}
{"id": "PMID:11575", "title": "Comparison of methods to wash liquid-stored red blood cells and red blood cells frozen with high or low concentrations of glycerol.", "content": "The efficiency of washing liquid-stored red blood cells and red blood cells frozen with high or low glycerol concentrations was evaluated by measuring the recovery of red blood cells in vitro, supernatant hemoglobin, extracellular potassium and red blood cell potassium levels, supernatant osmolality, residual 125I albumin, glycerol, hypoxanthine, and di-2-ethylhexyl phthalate (DEHP) levels. Four commercial washing systems were studied, three which used sodium chloride solutions with serial or continuous-flow centrifugation and one which used sugar solutions and dilution/agglomeration. Washing was most efficient using sodium chloride solutions in the IBM Blood Processor, an automated serial centrifugation procedure and in the Fenwal Elutramatic, a continuous-flow centrifugation procedure. Less efficient washing was achieved in the Haemonetics Processor 15, a continuous-flow centrifugation procedure and the least efficient washing occurred using the original and modified dilution/agglomeration procedures. To achieve the most efficient washing, three principles must be utilized: concentration of the red blood cells to hematocrit values of 90 per cent, prior to washing or freezing. Liquid-stored red blood cells concentrated to hematocrit values of 90V per cent should be diluted with hypertonic sodium chloride solutions prior to recovery and washing. Red blood cells containing 20 per cent or 40 per cent W/V glycerol should be diluted with hypertonic sodium chloride solutions before recovery and washing. Finally, on-line dilution should be achieved in the washing systems that use continuous-flow centrifugation.", "contents": "Comparison of methods to wash liquid-stored red blood cells and red blood cells frozen with high or low concentrations of glycerol. The efficiency of washing liquid-stored red blood cells and red blood cells frozen with high or low glycerol concentrations was evaluated by measuring the recovery of red blood cells in vitro, supernatant hemoglobin, extracellular potassium and red blood cell potassium levels, supernatant osmolality, residual 125I albumin, glycerol, hypoxanthine, and di-2-ethylhexyl phthalate (DEHP) levels. Four commercial washing systems were studied, three which used sodium chloride solutions with serial or continuous-flow centrifugation and one which used sugar solutions and dilution/agglomeration. Washing was most efficient using sodium chloride solutions in the IBM Blood Processor, an automated serial centrifugation procedure and in the Fenwal Elutramatic, a continuous-flow centrifugation procedure. Less efficient washing was achieved in the Haemonetics Processor 15, a continuous-flow centrifugation procedure and the least efficient washing occurred using the original and modified dilution/agglomeration procedures. To achieve the most efficient washing, three principles must be utilized: concentration of the red blood cells to hematocrit values of 90 per cent, prior to washing or freezing. Liquid-stored red blood cells concentrated to hematocrit values of 90V per cent should be diluted with hypertonic sodium chloride solutions prior to recovery and washing. Red blood cells containing 20 per cent or 40 per cent W/V glycerol should be diluted with hypertonic sodium chloride solutions before recovery and washing. Finally, on-line dilution should be achieved in the washing systems that use continuous-flow centrifugation."}
{"id": "PMID:11580", "title": "Absence of specific mixed leukocyte culture reactivity during graft-versus-host disease and following bone marrow transplant rejection.", "content": "Retrospective mixed leukocyte culture studies were performed in eight patients who had either rejected their marrow grafts or experienced graft-versus-host disease and in seven patients with successful marrow engraftment. In tests of pre-and post-transplant lymphocytes we found no evidence that rejection or graft-versus-host disease was caused by antigens that stimulate in the mixed lymphocyte culture assay.", "contents": "Absence of specific mixed leukocyte culture reactivity during graft-versus-host disease and following bone marrow transplant rejection. Retrospective mixed leukocyte culture studies were performed in eight patients who had either rejected their marrow grafts or experienced graft-versus-host disease and in seven patients with successful marrow engraftment. In tests of pre-and post-transplant lymphocytes we found no evidence that rejection or graft-versus-host disease was caused by antigens that stimulate in the mixed lymphocyte culture assay."}
{"id": "PMID:11576", "title": "Metabolic changes during platelet storage.", "content": "Platelet concentrates (PC) were stored in plastic bags with continuous shaking at 4, 22, and 37 C. Various metabolic parameters were examined over a 72-hour period. At 22 C, the pH and PO2 declined over 72 hours while the PCO2 and lactate increased. Hypotonic shock declined to 70 per cent. This differed from the small amounts of CO2 and lactate found at 4 C and the marked accumulation of metabolites and almost complete loss of shock response at 37 C. Aggregation was always better maintained with 4 C storage. The toxic effect of the accumulation of metabolites on the platelets was tested by adding lactate to fresh PC at zero time. This was effective in lowering the initial pH, markedly inhibiting the response to aggregation and decreasing the total accumulation of lactate during storage, but did not produce an inhibition of hypotonic shock response. The effect of accumulation of toxic metabolites was further investigated by using 72-hour plasma and platelets and recombining each of them with fresh preparations. Platelets were tested under degassed conditions to outline the requirements for oxygen and gasious exchange. Surprisingly, there was less accumulation of lactate and CO2 and better hypotonic shock response. These experiments have detected various changes in viability markers in platelets that are stored under actual blood bank conditions and indicate that the accumulation of lactate is not totally responsible for the toxic inhibition of platelet performance that is found upon storage at 22 C.", "contents": "Metabolic changes during platelet storage. Platelet concentrates (PC) were stored in plastic bags with continuous shaking at 4, 22, and 37 C. Various metabolic parameters were examined over a 72-hour period. At 22 C, the pH and PO2 declined over 72 hours while the PCO2 and lactate increased. Hypotonic shock declined to 70 per cent. This differed from the small amounts of CO2 and lactate found at 4 C and the marked accumulation of metabolites and almost complete loss of shock response at 37 C. Aggregation was always better maintained with 4 C storage. The toxic effect of the accumulation of metabolites on the platelets was tested by adding lactate to fresh PC at zero time. This was effective in lowering the initial pH, markedly inhibiting the response to aggregation and decreasing the total accumulation of lactate during storage, but did not produce an inhibition of hypotonic shock response. The effect of accumulation of toxic metabolites was further investigated by using 72-hour plasma and platelets and recombining each of them with fresh preparations. Platelets were tested under degassed conditions to outline the requirements for oxygen and gasious exchange. Surprisingly, there was less accumulation of lactate and CO2 and better hypotonic shock response. These experiments have detected various changes in viability markers in platelets that are stored under actual blood bank conditions and indicate that the accumulation of lactate is not totally responsible for the toxic inhibition of platelet performance that is found upon storage at 22 C."}
{"id": "PMID:11577", "title": "Freezing and deglycerolizing sickle-trait red blood cells.", "content": "Sickle-trait red blood cells respond to freezing and thawing like normal cells, but during deglycerolization by centrifugal methods, they pack and hemolyze. This appears to be the result of changes in surface characteristics with suspension in hyperosmotic saline and even modest increases in osmolality result in packing with centrifugation. Modifications to permit deglycerolization of sickle-trait cells have been designed for use with both the Haemonetics and the IBM cell washing systems. Sickle-trait cells do not agglomerate satisfactorily but we were unable to devise a modification of this deglycerolizing system that would accommodate sickle-trait cells.", "contents": "Freezing and deglycerolizing sickle-trait red blood cells. Sickle-trait red blood cells respond to freezing and thawing like normal cells, but during deglycerolization by centrifugal methods, they pack and hemolyze. This appears to be the result of changes in surface characteristics with suspension in hyperosmotic saline and even modest increases in osmolality result in packing with centrifugation. Modifications to permit deglycerolization of sickle-trait cells have been designed for use with both the Haemonetics and the IBM cell washing systems. Sickle-trait cells do not agglomerate satisfactorily but we were unable to devise a modification of this deglycerolizing system that would accommodate sickle-trait cells."}
{"id": "PMID:11582", "title": "Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells.", "content": "(1)Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. (2) Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. (3) Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. (4) The findings suggest that Tcells, at an early stage of differentiation, are more susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. (5) It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstituting and cellular engineering without producing GVHD.", "contents": "Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells. (1)Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. (2) Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. (3) Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. (4) The findings suggest that Tcells, at an early stage of differentiation, are more susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. (5) It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstituting and cellular engineering without producing GVHD."}
{"id": "PMID:11589", "title": "Graft-versus-leukemia for AKR spontaneous leukemia-lymphoma.", "content": "Adoptive immunotherapy in the form of a transient graft of mismatched DBA/2 BM + LN cells was used in combination with several chemoradiotherapy regimens to treat AKR mice bearing advanced SLL. Leukemic mice treated in this manner had a significant prolongation of their MST and significantly higher survival rates 60 and 90 days posttreatment than corresponding control groups. Syngeneic- or allogeneic-matched cells did not provide substantial GVL effect. An inverse relationship that influenced survival was observed between the radiation dose and the dose of GVL effector cells used to treat leukemic AKR mice in the treatment model. Recurrence leukemia remains a major problem.", "contents": "Graft-versus-leukemia for AKR spontaneous leukemia-lymphoma. Adoptive immunotherapy in the form of a transient graft of mismatched DBA/2 BM + LN cells was used in combination with several chemoradiotherapy regimens to treat AKR mice bearing advanced SLL. Leukemic mice treated in this manner had a significant prolongation of their MST and significantly higher survival rates 60 and 90 days posttreatment than corresponding control groups. Syngeneic- or allogeneic-matched cells did not provide substantial GVL effect. An inverse relationship that influenced survival was observed between the radiation dose and the dose of GVL effector cells used to treat leukemic AKR mice in the treatment model. Recurrence leukemia remains a major problem."}
{"id": "PMID:11601", "title": "Renal complications of drug addiction.", "content": "The kidney is one of the target organs involved as a consequence of the systemic complications seen in drug abusers. This may manifest itself in one of the following forms: acute hepatitis with modest proteinuria (less than 2 Gm. per day); bacterial endocarditis with hematuria, azotemia, and a focal or diffuse glomerulonephritis; the nephrotic syndrome with focal mesangial sclerosis and diffuse interstitial nephritis often pursuing a fulminant course terminating in uremia; acute renal failure secondary to rhabdomyolysis and myoglobinuria; polyarteritis nodosa with renal involvement; and obstructive uropathy secondary to fungus ball in the urinary tract.", "contents": "Renal complications of drug addiction. The kidney is one of the target organs involved as a consequence of the systemic complications seen in drug abusers. This may manifest itself in one of the following forms: acute hepatitis with modest proteinuria (less than 2 Gm. per day); bacterial endocarditis with hematuria, azotemia, and a focal or diffuse glomerulonephritis; the nephrotic syndrome with focal mesangial sclerosis and diffuse interstitial nephritis often pursuing a fulminant course terminating in uremia; acute renal failure secondary to rhabdomyolysis and myoglobinuria; polyarteritis nodosa with renal involvement; and obstructive uropathy secondary to fungus ball in the urinary tract."}
{"id": "PMID:11602", "title": "Spontaneous renal hemorrhage.", "content": "This report of 9 cases of spontaneous renal hemorrhage illustrates the wide variety of responsible conditions that may be found in a small series and the tendency for some of these conditions to coexist. In particular, all 3 patients with a bleeding diathesis had an associated anatomic lesion, and it was concluded that this group of patients required aggressive radiologic investigation. Three main clinical presentations were identified: sudden severe flank pain, symptomless hypertension, and a palpable mass with few or no symptoms. The radiologic signs are reviewed with emphasis on a recently described sign of streaky retroperitoneal fat. Treatment is discussed briefly.", "contents": "Spontaneous renal hemorrhage. This report of 9 cases of spontaneous renal hemorrhage illustrates the wide variety of responsible conditions that may be found in a small series and the tendency for some of these conditions to coexist. In particular, all 3 patients with a bleeding diathesis had an associated anatomic lesion, and it was concluded that this group of patients required aggressive radiologic investigation. Three main clinical presentations were identified: sudden severe flank pain, symptomless hypertension, and a palpable mass with few or no symptoms. The radiologic signs are reviewed with emphasis on a recently described sign of streaky retroperitoneal fat. Treatment is discussed briefly."}
{"id": "PMID:11607", "title": "[Effect of glutamic acid on the interrelationship of the effects of different activators of cerebral glutaminase].", "content": "When phosphate and tyroxine (activators of brain glutaminase) are used in small amounts, a potentiation of their stimulatory effect is observed. Higher concentrations exhibit an opposite effect. Glutamic acid has a strong inhibitory effect on all the activators of glutaminase given separately. The inhibitory effect of glutamate increases on lowering the pH. On the other hand the potentiation observed on adding two stimulators is increased greatly in the presence of glutamate. On the addition of tyroxine to other stimulators a greater potentiation and rise of glutaminase activity are observed. The potentiation, which occurs on the joint addition of phosphate and tyroxine, is raised with the increase of the amount of glutamic acid, while on the contrary on joining phosphate with other stimulators potentiation is reduced. Potentiation is variable and depends on the pH. Preincubation of brain mitochondrial fraction with guanidine chloride inhibits markedly the stimulatory effect of all the stimulators used, but their joint addition almost abolishes the potentiating effect. In the presence of glutamic acid, due to the increase of the cooperative effect between the two stimulators, glutaminase activity is greatly increased and sometimes its inhibitory effect is not even observed. The data obtained indicate that in brain glutamic acid in the presence of phosphate+thyroxine cannot be considered as an inhibitor of glutaminase and that the important factor here is not so much the absolute levels of the activators as their favorable combinations.", "contents": "[Effect of glutamic acid on the interrelationship of the effects of different activators of cerebral glutaminase]. When phosphate and tyroxine (activators of brain glutaminase) are used in small amounts, a potentiation of their stimulatory effect is observed. Higher concentrations exhibit an opposite effect. Glutamic acid has a strong inhibitory effect on all the activators of glutaminase given separately. The inhibitory effect of glutamate increases on lowering the pH. On the other hand the potentiation observed on adding two stimulators is increased greatly in the presence of glutamate. On the addition of tyroxine to other stimulators a greater potentiation and rise of glutaminase activity are observed. The potentiation, which occurs on the joint addition of phosphate and tyroxine, is raised with the increase of the amount of glutamic acid, while on the contrary on joining phosphate with other stimulators potentiation is reduced. Potentiation is variable and depends on the pH. Preincubation of brain mitochondrial fraction with guanidine chloride inhibits markedly the stimulatory effect of all the stimulators used, but their joint addition almost abolishes the potentiating effect. In the presence of glutamic acid, due to the increase of the cooperative effect between the two stimulators, glutaminase activity is greatly increased and sometimes its inhibitory effect is not even observed. The data obtained indicate that in brain glutamic acid in the presence of phosphate+thyroxine cannot be considered as an inhibitor of glutaminase and that the important factor here is not so much the absolute levels of the activators as their favorable combinations."}
{"id": "PMID:11613", "title": "Comparative studies on the N-oxidation of aniline and N,N-dimethylaniline by rabbit liver microsomes.", "content": "1. Rate studies of N-oxidation of aniline and N,N-dimethylaniline by rabbit liver microsomal preparations were performed at different pH values. The apparent pKs of the free functional groups were 7-2 and 6-9, respectively, at 26 degrees. The apparent heats of ionization of these groups varied from 26-8 to 31-8 kJ mol-1. 2. Photo-oxidation of the microsomal mixed function oxidase resulted in rapid loss of N-oxygenating activity. The enzyme was markedly protected from inactivation by the presence of aniline or N,N-dimethylaniline. The apparent KD values for protection were close to the Km and KS values for the individual arylamines. The pH profiles of the initial rates of photo-inactivation resembled the titration curves of groups with an apparent pKa between 6-0 and 6-2. 3. The N-oxidase was strongly inhibited by diethyl pyrocarbonate at pH 6-2. 3. The N-oxidase was strongly inhibited by diethyl pyrocarbonate at pH 6-0. Catalytic capacity was partially restored by treatment with neutral hydroxylamine. Pyridine protected the enzyme from acylation. 4. A close relationship exists between the N-hydroxylation of aniline and the N-oxide formation from N,N-dimethylaniline with respect to sensitivity to photo-oxidation, reactivity to protective substrates and susceptibility to carbethoxylation.", "contents": "Comparative studies on the N-oxidation of aniline and N,N-dimethylaniline by rabbit liver microsomes. 1. Rate studies of N-oxidation of aniline and N,N-dimethylaniline by rabbit liver microsomal preparations were performed at different pH values. The apparent pKs of the free functional groups were 7-2 and 6-9, respectively, at 26 degrees. The apparent heats of ionization of these groups varied from 26-8 to 31-8 kJ mol-1. 2. Photo-oxidation of the microsomal mixed function oxidase resulted in rapid loss of N-oxygenating activity. The enzyme was markedly protected from inactivation by the presence of aniline or N,N-dimethylaniline. The apparent KD values for protection were close to the Km and KS values for the individual arylamines. The pH profiles of the initial rates of photo-inactivation resembled the titration curves of groups with an apparent pKa between 6-0 and 6-2. 3. The N-oxidase was strongly inhibited by diethyl pyrocarbonate at pH 6-2. 3. The N-oxidase was strongly inhibited by diethyl pyrocarbonate at pH 6-0. Catalytic capacity was partially restored by treatment with neutral hydroxylamine. Pyridine protected the enzyme from acylation. 4. A close relationship exists between the N-hydroxylation of aniline and the N-oxide formation from N,N-dimethylaniline with respect to sensitivity to photo-oxidation, reactivity to protective substrates and susceptibility to carbethoxylation."}
{"id": "PMID:11614", "title": "Azo- and nitro-reductases of the cestode Moniezia expansa. Substrate specificity, reaction products and the effects of flavins and other compounds.", "content": "1. The effects of various inhibitors and activators on the azo- and nitro-reductases of Moniezia expansa have been studied. Both reductions were partially inhibited by FAD, FMN, riboflavin, allopurinol, dicoumarol, 5-nitro-2-furaldehyde, azide and cyanide at 1 mM. Both reactions were stimulated by hypoxanthine. Menadione, nitrofurantoin, SKF 525-A (2-diethylaminoethyl 2,2-diphenylvalerate) and fluoride were without effect. 2. Xanthine- and aldehyde-oxidase activities were not detected in the enzyme preparation. 3. The substrate specificity of the azo- and nitro-reductases were determined. Azobenzene, 4-dimethylamino-azobenzene and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene, nitrobenzene, 4-nitrohippuric acid and the isomers of nitrophenol, nitroanisole, nitrobenzoic acid, nitrobenzaldehyde and nitrobenzyl alcohol were reduced. Nitrobenzaldehyde isomers were not reduced to the alcohols and the coumaric acids were not reduced to the phenylpropionic acids. 4. The products of azo- and nitro-reduction were the corresponding amines; hydroxylamino- and hydrazo-compounds were not detected. 5. The pH optima and cofactor requirements were the same for both azo- and nitro-reduction. Neither reaction was inhibited by oxygen.", "contents": "Azo- and nitro-reductases of the cestode Moniezia expansa. Substrate specificity, reaction products and the effects of flavins and other compounds. 1. The effects of various inhibitors and activators on the azo- and nitro-reductases of Moniezia expansa have been studied. Both reductions were partially inhibited by FAD, FMN, riboflavin, allopurinol, dicoumarol, 5-nitro-2-furaldehyde, azide and cyanide at 1 mM. Both reactions were stimulated by hypoxanthine. Menadione, nitrofurantoin, SKF 525-A (2-diethylaminoethyl 2,2-diphenylvalerate) and fluoride were without effect. 2. Xanthine- and aldehyde-oxidase activities were not detected in the enzyme preparation. 3. The substrate specificity of the azo- and nitro-reductases were determined. Azobenzene, 4-dimethylamino-azobenzene and 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene, nitrobenzene, 4-nitrohippuric acid and the isomers of nitrophenol, nitroanisole, nitrobenzoic acid, nitrobenzaldehyde and nitrobenzyl alcohol were reduced. Nitrobenzaldehyde isomers were not reduced to the alcohols and the coumaric acids were not reduced to the phenylpropionic acids. 4. The products of azo- and nitro-reduction were the corresponding amines; hydroxylamino- and hydrazo-compounds were not detected. 5. The pH optima and cofactor requirements were the same for both azo- and nitro-reduction. Neither reaction was inhibited by oxygen."}
{"id": "PMID:11615", "title": "A new metabolic pathway of bromazepam involving attachment of a methylthio group.", "content": "1. The structures of three hitherto unidentified metabolites of bromazepam in the rat were elucidated using u.v., mass, n.m.r. and i.r. spectrometry. 2. All three metabolites contained a methylthio or corresponding oxidized group at the C-6' position of the pyridyl moiety. 3. Quantitative analysis of the metabolites determined after administration of [14C]bromazepam to rat revealed that the three metabolites together comprised about 6% of the total radioactivity excreted in the 24-h urine, or about 1% of the dose.", "contents": "A new metabolic pathway of bromazepam involving attachment of a methylthio group. 1. The structures of three hitherto unidentified metabolites of bromazepam in the rat were elucidated using u.v., mass, n.m.r. and i.r. spectrometry. 2. All three metabolites contained a methylthio or corresponding oxidized group at the C-6' position of the pyridyl moiety. 3. Quantitative analysis of the metabolites determined after administration of [14C]bromazepam to rat revealed that the three metabolites together comprised about 6% of the total radioactivity excreted in the 24-h urine, or about 1% of the dose."}
{"id": "PMID:11616", "title": "[Incidence of stress ulcer and secretion of gastric juice following truncal and selective vagotomy].", "content": "In rats development of stress ulcers by immobilization is accompanied by elevated pH, reduced amount of gastric juice, and by this with decreased amount of acid. Consequently, the acid factor has no primary importance for the development of stress ulcer. Truncal vagotomy, selective proximal vagotomy, and selective antral vagotomy result in reducing the acid secretion at elevated pH value and increased juice amount, and in a decreased ulcer rate. Greatest certainty to prevent stress ulcer gives the truncal vagotomy, whereas there is a poor effect after antral vagotomy.", "contents": "[Incidence of stress ulcer and secretion of gastric juice following truncal and selective vagotomy]. In rats development of stress ulcers by immobilization is accompanied by elevated pH, reduced amount of gastric juice, and by this with decreased amount of acid. Consequently, the acid factor has no primary importance for the development of stress ulcer. Truncal vagotomy, selective proximal vagotomy, and selective antral vagotomy result in reducing the acid secretion at elevated pH value and increased juice amount, and in a decreased ulcer rate. Greatest certainty to prevent stress ulcer gives the truncal vagotomy, whereas there is a poor effect after antral vagotomy."}
{"id": "PMID:11617", "title": "Influence of alpha-adrenergic block and beta-adrenergic stimulation on distribution of cardiac output after cardiopulmonary bypass.", "content": "Organ and tissue damage restricts total cardiopulmonary bypass to a few hours in patients. The cause might be the disturbance of tissue flow in which the sympatho-adrenal hyper-activity plays a decisive role. In dogs, killed 30 min after cardiopulmonary bypass was stopped, we studied the tissue distribution of cardiac output with the method of Sapirstein. In one group the alpha-adrenergic blocker, in the other one the beta-adrenergic stimulator was continuously applied during the whole operation-period. Compared to a control group the per cent of cardiac output as well as the regional tissue flow after alpha-adrenergic block increased in the liver, ileum, adrenals, testes, kidney and in the skin and decreased in the spleen and thyroid gland. After beta-adrenergic stimulation the per cent of cardiac output increased in the heart muscle, lungs, liver, ileum, adrenals and m. soleus and decreased in the spleen and thyroid gland. The absolute values of organ tissue flow increased in ileum and decreased in the spleen, thyroid gland and in the kidney.", "contents": "Influence of alpha-adrenergic block and beta-adrenergic stimulation on distribution of cardiac output after cardiopulmonary bypass. Organ and tissue damage restricts total cardiopulmonary bypass to a few hours in patients. The cause might be the disturbance of tissue flow in which the sympatho-adrenal hyper-activity plays a decisive role. In dogs, killed 30 min after cardiopulmonary bypass was stopped, we studied the tissue distribution of cardiac output with the method of Sapirstein. In one group the alpha-adrenergic blocker, in the other one the beta-adrenergic stimulator was continuously applied during the whole operation-period. Compared to a control group the per cent of cardiac output as well as the regional tissue flow after alpha-adrenergic block increased in the liver, ileum, adrenals, testes, kidney and in the skin and decreased in the spleen and thyroid gland. After beta-adrenergic stimulation the per cent of cardiac output increased in the heart muscle, lungs, liver, ileum, adrenals and m. soleus and decreased in the spleen and thyroid gland. The absolute values of organ tissue flow increased in ileum and decreased in the spleen, thyroid gland and in the kidney."}
{"id": "PMID:11621", "title": "[On the effect of particulate airborne substances on various micro-organisms (author's transl)].", "content": "Experimental studies on the reaction of micro-organisms on fine-dust filters (type C) and high-efficiency particulate air filters (type R and S) have shown no evidence of a growth of microorganisms. Therefore efforts were aimed at detecting antimicrobial factors which were supposed to exist in the precipitated acidic continental aerosol. With this in mind, air filters from different locations and with service times were extracted in water and the extract was tested for its antimicrobial effects. Die-off rates are used to demonstrate the influence of such extracts with varying concentrations of substances and pH values on bacteria.", "contents": "[On the effect of particulate airborne substances on various micro-organisms (author's transl)]. Experimental studies on the reaction of micro-organisms on fine-dust filters (type C) and high-efficiency particulate air filters (type R and S) have shown no evidence of a growth of microorganisms. Therefore efforts were aimed at detecting antimicrobial factors which were supposed to exist in the precipitated acidic continental aerosol. With this in mind, air filters from different locations and with service times were extracted in water and the extract was tested for its antimicrobial effects. Die-off rates are used to demonstrate the influence of such extracts with varying concentrations of substances and pH values on bacteria."}
{"id": "PMID:11622", "title": "[On the enzymatics of the microbial breakdown of pyrazone (author's transl)].", "content": "From samples of earth taken in different parts of the world bacteria were isolated which grow on pyrazone as the only source of carbon. When these bacteria are grown in a pyrazone mineral salt medium, four compounds are excreted into the medium. The structures of these compounds furnish information on the catabolic route of pyrazone. Since the suggested scheme of breakdown was incomplete, enzymatic tests were carried out to clarify the matter. It was possible to carry out the first steps of breakdown also in the cell-free extract of the pyrazone-degrading bacteria. For the second step of pyrazone breakdown, 2 different enzymes of the same catalytic activity were identified. For the oxidative cleavage of the pyrocatechole derivative 2 different enzymes were found: an ortho- and a meta-clearing enzyme. The 2-hydroxy muconic acid decarboxylase was identified as a further enzyme. The importance of this enzyme is discussed in connection with the further breakdown.", "contents": "[On the enzymatics of the microbial breakdown of pyrazone (author's transl)]. From samples of earth taken in different parts of the world bacteria were isolated which grow on pyrazone as the only source of carbon. When these bacteria are grown in a pyrazone mineral salt medium, four compounds are excreted into the medium. The structures of these compounds furnish information on the catabolic route of pyrazone. Since the suggested scheme of breakdown was incomplete, enzymatic tests were carried out to clarify the matter. It was possible to carry out the first steps of breakdown also in the cell-free extract of the pyrazone-degrading bacteria. For the second step of pyrazone breakdown, 2 different enzymes of the same catalytic activity were identified. For the oxidative cleavage of the pyrocatechole derivative 2 different enzymes were found: an ortho- and a meta-clearing enzyme. The 2-hydroxy muconic acid decarboxylase was identified as a further enzyme. The importance of this enzyme is discussed in connection with the further breakdown."}
{"id": "PMID:11623", "title": "[Determination of the toxicity of industrial waste by means of a bacterial test (author's transl)].", "content": "The decision on whether industrial waste should be deposited on general or special dumps depends upon the toxicity of the waste and thus upon the risk of ground-water pollution and the killing off of micro-organisms responsible for breaking down waste products. Since chemical analyses that are to provide information on toxicity are frequently very costly, an attempt was made to determine the toxicity of solid or semi-solid waste with the aid of a bacterial test. As in the perforated-plate test, here, too, the formation and size of inhibition zones were used to determine the toxicity after diffusion of substances contained in industrial waste. About 30 different types of industrial waste were examined with this method. For almost all substances a positive correlation of the (known) constituents of waste to the formation of inhibition zones was found to exist. The influence exercised by solubility and diffusibility and other problems are dealt with.", "contents": "[Determination of the toxicity of industrial waste by means of a bacterial test (author's transl)]. The decision on whether industrial waste should be deposited on general or special dumps depends upon the toxicity of the waste and thus upon the risk of ground-water pollution and the killing off of micro-organisms responsible for breaking down waste products. Since chemical analyses that are to provide information on toxicity are frequently very costly, an attempt was made to determine the toxicity of solid or semi-solid waste with the aid of a bacterial test. As in the perforated-plate test, here, too, the formation and size of inhibition zones were used to determine the toxicity after diffusion of substances contained in industrial waste. About 30 different types of industrial waste were examined with this method. For almost all substances a positive correlation of the (known) constituents of waste to the formation of inhibition zones was found to exist. The influence exercised by solubility and diffusibility and other problems are dealt with."}
{"id": "PMID:11624", "title": "[The effect of pH value and temperature on the stability of L-aminoacidoxidase from the venom of the sand viper].", "content": "The stability of highly purified L-amino acid oxidase from the sand viper venom remains practically unaffected by the pH-value at 4degreesC between pH 5 and 8, whereas a sharp activity fall was observed on both sides of this range. At temperatures above 30 degreesC the enzyme is stable only at pH 5.0--5.5. The inactivation pH values above 5.5 follows a first-order rate equation with characteristic changes in the absorption and emission spectra of the enzyme. The stability of the enzyme is dependent on the temperature of storage. At pH 7.5 there is a stability minimum at --10 degrees and -- 30 degreesC. At -- 72 degreesC the enzyme is stable practically for an unlimited period of time; temperatures exceeding 50 degrees C rapidly lead to complete inactivation. Also in the cold, the L-amino acid oxidase is most stable at pH 5.5. There are characteristic changes in absorption and emission spectra in the temperature-stability minimum (--15 degreesC) and at temperatures above 30degreesC. The inactivations follow a first-order rate equation. The cold inactivation is reversible. The stability of the enzyme is diminished by some anions and cations at 37 degreesC. The cold inactivation is promoted by several inorganic anions; organic anions and ammonium sulfate prevent cold inactivation.", "contents": "[The effect of pH value and temperature on the stability of L-aminoacidoxidase from the venom of the sand viper]. The stability of highly purified L-amino acid oxidase from the sand viper venom remains practically unaffected by the pH-value at 4degreesC between pH 5 and 8, whereas a sharp activity fall was observed on both sides of this range. At temperatures above 30 degreesC the enzyme is stable only at pH 5.0--5.5. The inactivation pH values above 5.5 follows a first-order rate equation with characteristic changes in the absorption and emission spectra of the enzyme. The stability of the enzyme is dependent on the temperature of storage. At pH 7.5 there is a stability minimum at --10 degrees and -- 30 degreesC. At -- 72 degreesC the enzyme is stable practically for an unlimited period of time; temperatures exceeding 50 degrees C rapidly lead to complete inactivation. Also in the cold, the L-amino acid oxidase is most stable at pH 5.5. There are characteristic changes in absorption and emission spectra in the temperature-stability minimum (--15 degreesC) and at temperatures above 30degreesC. The inactivations follow a first-order rate equation. The cold inactivation is reversible. The stability of the enzyme is diminished by some anions and cations at 37 degreesC. The cold inactivation is promoted by several inorganic anions; organic anions and ammonium sulfate prevent cold inactivation."}
{"id": "PMID:11626", "title": "Retransfusion acidosis after brief haemorrhagic hypotension in the dog.", "content": "Dogs under chloralose anasthesia were bled at a rate of 50 ml/min to a total of 25 ml/kg body weight and 2 minutes later a quick reinfusion of adequate volumes of blood, dextran, or Locke's solution was done. Within 2 minutes after reinfusion, the pH of arterial blood fell by 0.074--0.127; concurrently, PaCO2 rose by 9.2-12.9 mm Hg. A close correlation was demonstrated between these changes. After retransfusion, PaO2 and the arterial lactic acid level did not change significantly. Thus retransfusion acidosis in the dog appears after a brief hypotensive period, too, but cannot be attributed to a \"washout\" of lactate from the tissues.", "contents": "Retransfusion acidosis after brief haemorrhagic hypotension in the dog. Dogs under chloralose anasthesia were bled at a rate of 50 ml/min to a total of 25 ml/kg body weight and 2 minutes later a quick reinfusion of adequate volumes of blood, dextran, or Locke's solution was done. Within 2 minutes after reinfusion, the pH of arterial blood fell by 0.074--0.127; concurrently, PaCO2 rose by 9.2-12.9 mm Hg. A close correlation was demonstrated between these changes. After retransfusion, PaO2 and the arterial lactic acid level did not change significantly. Thus retransfusion acidosis in the dog appears after a brief hypotensive period, too, but cannot be attributed to a \"washout\" of lactate from the tissues."}
{"id": "PMID:11629", "title": "[Gamma-glutamyl-transpeptidase in alcoholic liver diseases].", "content": "In well defined liver diseases in 69 alcoholics and in 71 patients without history of alcoholism the enzymatic findings were compared. Also a group of 43 alcoholics with praedelirium or delirium tremens were examined. In steatosis due to alcohol, the average of GGTP (145 U/l) attains values two times higher than in comparable cases of non-alcoholic origin (73 U/l). In cirrhotics with alcoholism, the average GGTP levels (477 U/l) exceed those obtained in patients with cirrhosis of other origin (110 U/l), four times more. Similar or higher GGTP values were found only in primary biliary cirrhosis. After a period of at least 3 months of abstinence, GGTP values had decreased (to 68 U/l) in the average). The highest values of GGTP were found in acute alcoholic hepatitis and in chronic alcoholics with praedelirium or delirium tremens. GGTP accords diagnostic hints in comparison with other enzymes, as shown by a quotient of GGTP-GPT. GGTP is very helpful for differentiation and long time observation of alcoholic liver disease, especially with regards controlling abstinence of alcohol.", "contents": "[Gamma-glutamyl-transpeptidase in alcoholic liver diseases]. In well defined liver diseases in 69 alcoholics and in 71 patients without history of alcoholism the enzymatic findings were compared. Also a group of 43 alcoholics with praedelirium or delirium tremens were examined. In steatosis due to alcohol, the average of GGTP (145 U/l) attains values two times higher than in comparable cases of non-alcoholic origin (73 U/l). In cirrhotics with alcoholism, the average GGTP levels (477 U/l) exceed those obtained in patients with cirrhosis of other origin (110 U/l), four times more. Similar or higher GGTP values were found only in primary biliary cirrhosis. After a period of at least 3 months of abstinence, GGTP values had decreased (to 68 U/l) in the average). The highest values of GGTP were found in acute alcoholic hepatitis and in chronic alcoholics with praedelirium or delirium tremens. GGTP accords diagnostic hints in comparison with other enzymes, as shown by a quotient of GGTP-GPT. GGTP is very helpful for differentiation and long time observation of alcoholic liver disease, especially with regards controlling abstinence of alcohol."}
{"id": "PMID:11630", "title": "Hepatic blood flow and cardiac output during Fluoromar anaesthesia. An animal study.", "content": "Related values of cardiac output and hepatic blood flow were measured in eight premedicated (pethidine 10 mg/kg b.w.) dogs under varying depths of fluoromar anaesthesia. The measurements were first taken under basis anaesthesia with barbiturate (mebumal natrium 25 mg/kg b.w.) gallamine (80 mg)-N2O-O-O2 (ratio 2 to 1) with controlled normoventilation, and then under increasing depths of fluoromar anaesthesia: increasing stepwise to 1 1/2-3 and 6% inspiratory concentrations. Finally the measurements were repeated after the fluoromar had been discontinued. Using the basis anaesthesia as a reference, it was found that 6% fluoromar gave a reduction in cardiac output (34%), heart rate (11%) and mean pressure in the aorta (18%). The peripheral resistance was simultaneously increased by 22%. The effect on the splanchnic blood flow was far less and without significant changes from one step in the anaesthesia to the next. Using 6% fluoromar it was found that there was a maximum reduction in blood flow of 20% of the initial value. There was unchanged splanchnic resistance during the whole of the investigation. After discontinuation of the fluoromar for 15 min and continued controlled ventilation (O2-N2O), rising heart rate and blood pressure were observed; however, cardiac output and splanchnic blood flow were unchanged. Corresponding to this, an additional increase in peripheral resistance of 10% and an insignificant increase of 5% in the splanchnic resistance were observed.", "contents": "Hepatic blood flow and cardiac output during Fluoromar anaesthesia. An animal study. Related values of cardiac output and hepatic blood flow were measured in eight premedicated (pethidine 10 mg/kg b.w.) dogs under varying depths of fluoromar anaesthesia. The measurements were first taken under basis anaesthesia with barbiturate (mebumal natrium 25 mg/kg b.w.) gallamine (80 mg)-N2O-O-O2 (ratio 2 to 1) with controlled normoventilation, and then under increasing depths of fluoromar anaesthesia: increasing stepwise to 1 1/2-3 and 6% inspiratory concentrations. Finally the measurements were repeated after the fluoromar had been discontinued. Using the basis anaesthesia as a reference, it was found that 6% fluoromar gave a reduction in cardiac output (34%), heart rate (11%) and mean pressure in the aorta (18%). The peripheral resistance was simultaneously increased by 22%. The effect on the splanchnic blood flow was far less and without significant changes from one step in the anaesthesia to the next. Using 6% fluoromar it was found that there was a maximum reduction in blood flow of 20% of the initial value. There was unchanged splanchnic resistance during the whole of the investigation. After discontinuation of the fluoromar for 15 min and continued controlled ventilation (O2-N2O), rising heart rate and blood pressure were observed; however, cardiac output and splanchnic blood flow were unchanged. Corresponding to this, an additional increase in peripheral resistance of 10% and an insignificant increase of 5% in the splanchnic resistance were observed."}
{"id": "PMID:11631", "title": "Regulation of the cyclic guanosine 3'-5' monophosphate system in human brain tumors.", "content": "Several reports have suggested that cylcic guanosine 3'-5' monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) are involved in the regulation of cellular proliferation. Following our previous reports on the cAMP system in human brain tumors, we decided to investigate the cGMP system in the same pathological tissues by studying the activity of guanylate cyclase and cGMP-phosphodiesterase (cGMP-PDE). We found that the activity of both enzymes is lower in neurinomas and glioblastomas than in meningiomas or in normal cerebral cortex. Furthermore, the subcellular distribution of guanylate cyclase in human cerebral cortex differs from that of neurinomas and glioblastomas. On the basis of such observations we have discussed the possibility that the regulatory mechanism of the enzymes related to the cyclic nucleotide metabolism is altered in brain tumors.", "contents": "Regulation of the cyclic guanosine 3'-5' monophosphate system in human brain tumors. Several reports have suggested that cylcic guanosine 3'-5' monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) are involved in the regulation of cellular proliferation. Following our previous reports on the cAMP system in human brain tumors, we decided to investigate the cGMP system in the same pathological tissues by studying the activity of guanylate cyclase and cGMP-phosphodiesterase (cGMP-PDE). We found that the activity of both enzymes is lower in neurinomas and glioblastomas than in meningiomas or in normal cerebral cortex. Furthermore, the subcellular distribution of guanylate cyclase in human cerebral cortex differs from that of neurinomas and glioblastomas. On the basis of such observations we have discussed the possibility that the regulatory mechanism of the enzymes related to the cyclic nucleotide metabolism is altered in brain tumors."}
{"id": "PMID:11632", "title": "Exposure to drugs and other possibly harmful factors during the first trimester of pregnancy. Comparison of two prospective studies performed in Sweden 10 years apart.", "content": "474 women in mid-pregnancy, interviewed at ten different hospitals in Sweden, were questioned on a number of social and medical items: e.g., drug use, contraceptive technique used before pregnancy, exposure to possibly deleterious factors in the environment. The study, compared with a similar study made ten years earlier in Sweden, showed little or no difference in the use of iron and/or vitamin preparations, analgesic drugs, antibiotics, or endocrine drugs; but a drastic reduction is noted in the use of psychotropic drugs and of antihistaminic drugs. A marked decrease in frequency of first trimester X-ray exposures can be found, but no marked changes in smoking habits. Appr. 18% of the women used contraceptive pills within 6 months of becoming pregnant---3 had used them during early pregnancy. About 4% (18 women) had used IUD---one became pregnant with a Cu-UID (intra-uterine device inpregnated with copper).This type of study can provide some information on the prevalence of relatively common factors, but it must be considerably extended in order to permit an analysis of rare events, e.g., use of most drugs.", "contents": "Exposure to drugs and other possibly harmful factors during the first trimester of pregnancy. Comparison of two prospective studies performed in Sweden 10 years apart. 474 women in mid-pregnancy, interviewed at ten different hospitals in Sweden, were questioned on a number of social and medical items: e.g., drug use, contraceptive technique used before pregnancy, exposure to possibly deleterious factors in the environment. The study, compared with a similar study made ten years earlier in Sweden, showed little or no difference in the use of iron and/or vitamin preparations, analgesic drugs, antibiotics, or endocrine drugs; but a drastic reduction is noted in the use of psychotropic drugs and of antihistaminic drugs. A marked decrease in frequency of first trimester X-ray exposures can be found, but no marked changes in smoking habits. Appr. 18% of the women used contraceptive pills within 6 months of becoming pregnant---3 had used them during early pregnancy. About 4% (18 women) had used IUD---one became pregnant with a Cu-UID (intra-uterine device inpregnated with copper).This type of study can provide some information on the prevalence of relatively common factors, but it must be considerably extended in order to permit an analysis of rare events, e.g., use of most drugs."}
{"id": "PMID:11633", "title": "Correlation of maternal physical fitness during pregnancy with maternal and fetal pH and lactic acid at delivery.", "content": "The physical fitness of 120 healthy primigravidae was determined two weeks before term using first the standardized three-stage submaximal work test on the following day the voluntarily maximal pulse-conducted work test on a bicycle ergometer. After the first test the level of lactic acid in the capillary circulation of 115 mothers was examined. Immediately after delivery the pH and the level of lactic acid in the maternal artery, umbilical vein and umbilical artery were determined. The level of lactic acid after the work test was negatively correlated with the physical performance of the mother. The level of lactic acid in the mother after the work test and the levels of lactic acid in the umbilical vessels were positively correlated. The mean pH value in physically fit women after delivery was almost significantly higher than in the women of below average performance. The pH level in the umbilical artery was also almost significantly higher in the mothers with above average performance. The physically fit women appear to work more during delivery than the less fit mothers, as the level of lactic acid after the delivery was as high as or higher than in mothers with a physical performance below average. The physical fitness of six mothers, who delivered an asphyxiated baby, was almost significantly lower than the performance of the mothers. Five mothers with an exceptionally high pH after delivery had a significantly higher performance than the other mothers.", "contents": "Correlation of maternal physical fitness during pregnancy with maternal and fetal pH and lactic acid at delivery. The physical fitness of 120 healthy primigravidae was determined two weeks before term using first the standardized three-stage submaximal work test on the following day the voluntarily maximal pulse-conducted work test on a bicycle ergometer. After the first test the level of lactic acid in the capillary circulation of 115 mothers was examined. Immediately after delivery the pH and the level of lactic acid in the maternal artery, umbilical vein and umbilical artery were determined. The level of lactic acid after the work test was negatively correlated with the physical performance of the mother. The level of lactic acid in the mother after the work test and the levels of lactic acid in the umbilical vessels were positively correlated. The mean pH value in physically fit women after delivery was almost significantly higher than in the women of below average performance. The pH level in the umbilical artery was also almost significantly higher in the mothers with above average performance. The physically fit women appear to work more during delivery than the less fit mothers, as the level of lactic acid after the delivery was as high as or higher than in mothers with a physical performance below average. The physical fitness of six mothers, who delivered an asphyxiated baby, was almost significantly lower than the performance of the mothers. Five mothers with an exceptionally high pH after delivery had a significantly higher performance than the other mothers."}
{"id": "PMID:11634", "title": "Serum gamma-glutamyl transpeptidase activity and urinary D-glucaric acid excretion in newborns in the first week of life. Effects of phenobarbital and nicethamide combination.", "content": "High serum gamma-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of phenobarbital and nicethamide an increase of gamma-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.", "contents": "Serum gamma-glutamyl transpeptidase activity and urinary D-glucaric acid excretion in newborns in the first week of life. Effects of phenobarbital and nicethamide combination. High serum gamma-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of phenobarbital and nicethamide an increase of gamma-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution."}
{"id": "PMID:11635", "title": "Enzyme histochemical study on fat-storing cells (so-called Ito's cell) of liver.", "content": "Inorder to gain a foothold in clarifying the functional significance of fatstoring cells, an enzyme histochemical study on these cells was carried out. Fat-storing cells showed no alkaline phosphatase, acid phosphatase or esterase activity but demonstrated a marked gamma-glutamyl transpeptidase activity suggesting the possibility of its participation in the synthesis of fiber protein. This possibility was further heightened by its remarkable activity noted at the site of progressive fibrosis. Fat-storing cells under a normal condition partake in the formation of fibers supporting the sinusoidal wall, and under an abnormal condition gradually change their shape with loss of fat droplets and then transform into fibroblast-like cells closely related to the progress of fibrosis.", "contents": "Enzyme histochemical study on fat-storing cells (so-called Ito's cell) of liver. Inorder to gain a foothold in clarifying the functional significance of fatstoring cells, an enzyme histochemical study on these cells was carried out. Fat-storing cells showed no alkaline phosphatase, acid phosphatase or esterase activity but demonstrated a marked gamma-glutamyl transpeptidase activity suggesting the possibility of its participation in the synthesis of fiber protein. This possibility was further heightened by its remarkable activity noted at the site of progressive fibrosis. Fat-storing cells under a normal condition partake in the formation of fibers supporting the sinusoidal wall, and under an abnormal condition gradually change their shape with loss of fat droplets and then transform into fibroblast-like cells closely related to the progress of fibrosis."}
{"id": "PMID:11636", "title": "A simple procedure for the purification of staphylococcal alpha-toxin.", "content": "Staphylococcal alpha-toxin was produced in a fluid medium based on acid hydrolysed casein using strain Wood 46. alpha-Toxin and several other proteins were precipitated from bacteria-free culture supernatants by heating at 60 degrees C for 20 min. The process was influenced by the pH of the solution. The toxin was completely inactivated and the precipitate contained a number of proteins if the pH of the solution was adjusted to 4.0-5.0. Heat precipitation of solutions having a pH of 6.0-7.0 resulted in a partial inactivation of alpha-toxin. The precipitates at this pH contained less of the additional proteins and had higher relative amounts of alpha-toxin than precipitates formed at a lower pH. The precipitate was dissolved in 8 M urea with the resultant activation of the haemolysin. Pure alpha-toxin with a molecular weight of 39,000 was obtained by electrophoresis in 8 M urea at pH 8.6 in ordinary tubes for polyacrylamide electrophoresis. The separation time was 45 min. The minor component of alpha-toxin with a pI of 7.4 could be demonstrated by the same method. A non-haemolytic protein with a molecular weight of 27,500 which existed in at least two charged forms, was shown to have an antigenic relationship to the toxin with a molecular weight of 39,000.", "contents": "A simple procedure for the purification of staphylococcal alpha-toxin. Staphylococcal alpha-toxin was produced in a fluid medium based on acid hydrolysed casein using strain Wood 46. alpha-Toxin and several other proteins were precipitated from bacteria-free culture supernatants by heating at 60 degrees C for 20 min. The process was influenced by the pH of the solution. The toxin was completely inactivated and the precipitate contained a number of proteins if the pH of the solution was adjusted to 4.0-5.0. Heat precipitation of solutions having a pH of 6.0-7.0 resulted in a partial inactivation of alpha-toxin. The precipitates at this pH contained less of the additional proteins and had higher relative amounts of alpha-toxin than precipitates formed at a lower pH. The precipitate was dissolved in 8 M urea with the resultant activation of the haemolysin. Pure alpha-toxin with a molecular weight of 39,000 was obtained by electrophoresis in 8 M urea at pH 8.6 in ordinary tubes for polyacrylamide electrophoresis. The separation time was 45 min. The minor component of alpha-toxin with a pI of 7.4 could be demonstrated by the same method. A non-haemolytic protein with a molecular weight of 27,500 which existed in at least two charged forms, was shown to have an antigenic relationship to the toxin with a molecular weight of 39,000."}
{"id": "PMID:11637", "title": "Some physicochemical properties of human leucocyte migration inhibitory factor (LIF).", "content": "Leucocyte migration inhibitory factor (LIF) obtained from human lymphocytes stimulated with concanavalin A was consistently and irreversibly blocked by the serine-esterase inhibitor phenyl-methyl sulphonylfuoride (PMSF). This effect was not due to fluoride ions, hydrolysis products of PMSF or to impurities. PMSF pulse treatment of human buffy coat cells did not affect cell migration under agarose. LIF was also irreversibly destroyed by treatment with L-cysteine and 2-mercapto-ethanol, suggesting that the molecule contains disulphide linkage groups decisive for its configuration and biological activity. Di-sodium EDTA completely inhibited LIF activity but only if present during the entire migration period. Removal of EDTA before LIF assay restored LIF activity. Leucotye migration was neighter influenced by L-cysteine nor by EDTA. LIF activity was slightly diminished after treatment at 56 degrees C for 1 h and completely lost at 80 degrees C for 1/2 h. Furthermore, LIF appeared rather stable when treated at pH values between 4 and 11. These findings suggest, but do not prove, an esterase or a protease nature of human LIF.", "contents": "Some physicochemical properties of human leucocyte migration inhibitory factor (LIF). Leucocyte migration inhibitory factor (LIF) obtained from human lymphocytes stimulated with concanavalin A was consistently and irreversibly blocked by the serine-esterase inhibitor phenyl-methyl sulphonylfuoride (PMSF). This effect was not due to fluoride ions, hydrolysis products of PMSF or to impurities. PMSF pulse treatment of human buffy coat cells did not affect cell migration under agarose. LIF was also irreversibly destroyed by treatment with L-cysteine and 2-mercapto-ethanol, suggesting that the molecule contains disulphide linkage groups decisive for its configuration and biological activity. Di-sodium EDTA completely inhibited LIF activity but only if present during the entire migration period. Removal of EDTA before LIF assay restored LIF activity. Leucotye migration was neighter influenced by L-cysteine nor by EDTA. LIF activity was slightly diminished after treatment at 56 degrees C for 1 h and completely lost at 80 degrees C for 1/2 h. Furthermore, LIF appeared rather stable when treated at pH values between 4 and 11. These findings suggest, but do not prove, an esterase or a protease nature of human LIF."}
{"id": "PMID:11642", "title": "A study of the relationship between the electrocardiogram and hemodynamics in the fetal lamb during asphyxia.", "content": "Progressive changes in the S-T interval of the fetal ECG were studied in 22 lamb fetuses, acutely exteriorized and submitted to graded hypoxia. The ECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure and combined cardiac output, estimated by the thermodilution method, as well as with blood gases and acid-base status. Close correlations were obtained between PaO2, pH and base deficit and the severity of ECG changes, graded according to a scoring system. Alterations in the ECG pattern consistently preceeded signs of failing cardiovascular function. Our previous findings indicated that the hypoxic ECG changes could be regarded as a sign of myocardial glycolysis. Accordingly, similar progressive ECG changes could be induced by isoprenaline injections. It is concluded that progressive changes of the S-T interval of the fetal ECG contains information about fetal hypoxic stress before signs of failing cardiovascular function are seen.", "contents": "A study of the relationship between the electrocardiogram and hemodynamics in the fetal lamb during asphyxia. Progressive changes in the S-T interval of the fetal ECG were studied in 22 lamb fetuses, acutely exteriorized and submitted to graded hypoxia. The ECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure and combined cardiac output, estimated by the thermodilution method, as well as with blood gases and acid-base status. Close correlations were obtained between PaO2, pH and base deficit and the severity of ECG changes, graded according to a scoring system. Alterations in the ECG pattern consistently preceeded signs of failing cardiovascular function. Our previous findings indicated that the hypoxic ECG changes could be regarded as a sign of myocardial glycolysis. Accordingly, similar progressive ECG changes could be induced by isoprenaline injections. It is concluded that progressive changes of the S-T interval of the fetal ECG contains information about fetal hypoxic stress before signs of failing cardiovascular function are seen."}
{"id": "PMID:11643", "title": "Non-pharmacological factors in drug treatment of anxiety states.", "content": "Forty-six outpatients with anxiety tension states took part in a study on the effects of anxiolytic drugs. After the first interview the subjects also filled in a questionnaire as to their expectations of treatment outcome (n=41) and their experience of the first consultation (n=42), and the doctors made a prognostic evaluation (n=46). The relations between these three factors and background variables as well as initial ratings and outcome as rated by the doctors at follow-up examinations after 2, 4, and 8 weeks were investigated. Expectations, experience, and prognosis were not related to each other. Less hopeful patients more often considered conflicts to be the exclusive cause of their disorder and they were rated higher on signs and on the variable difficulties in being with people. Patients with less favourable experience more often considered practical and economic difficulties to be a cause of their disorder. Single or divorced patients were more often judged to have a less favourable prognosis. More positive expectations and a favourable prognosis. More positive expectations and a favourable prognosis were to some extent related to a better outcome after 2 and 4 weeks and a favourable experience was to some extent related to a better outcome after 4 and 8 weeks.", "contents": "Non-pharmacological factors in drug treatment of anxiety states. Forty-six outpatients with anxiety tension states took part in a study on the effects of anxiolytic drugs. After the first interview the subjects also filled in a questionnaire as to their expectations of treatment outcome (n=41) and their experience of the first consultation (n=42), and the doctors made a prognostic evaluation (n=46). The relations between these three factors and background variables as well as initial ratings and outcome as rated by the doctors at follow-up examinations after 2, 4, and 8 weeks were investigated. Expectations, experience, and prognosis were not related to each other. Less hopeful patients more often considered conflicts to be the exclusive cause of their disorder and they were rated higher on signs and on the variable difficulties in being with people. Patients with less favourable experience more often considered practical and economic difficulties to be a cause of their disorder. Single or divorced patients were more often judged to have a less favourable prognosis. More positive expectations and a favourable prognosis. More positive expectations and a favourable prognosis were to some extent related to a better outcome after 2 and 4 weeks and a favourable experience was to some extent related to a better outcome after 4 and 8 weeks."}
{"id": "PMID:11645", "title": "A comparison of drug use among Houston and lower Rio Grande valley secondary students.", "content": "The authors conducted a study of drug use among students of a predominantly Mexican-American population and compared their findings with a similar study that was done in a large urban setting. They suggest that drug use among Mexican-American secondary students is less than among Anglo secondary students, which is opposite to popular lay notions.", "contents": "A comparison of drug use among Houston and lower Rio Grande valley secondary students. The authors conducted a study of drug use among students of a predominantly Mexican-American population and compared their findings with a similar study that was done in a large urban setting. They suggest that drug use among Mexican-American secondary students is less than among Anglo secondary students, which is opposite to popular lay notions."}
{"id": "PMID:11649", "title": "Chlorination, decarboxylation and bactericidal activity mediated by the MPO-H2O2-C1- system.", "content": "1. MPO, H2O2 and C1- form a complex that undergoes intramolecular rearrangement yielding the chlorinium ion. 2. The chlorinium ion can interact with MPO, bacteria and amino acids. 3. The reaction can occur at a wide range of pH, H2O2 concentration and C1- concentration. 4. The chlorinium ion can attack different protein molecules to cause structural changes. 5. Preincubation of MPO with bacteria results in greater bactericidal activity. 6. Diffusible bactericidal agents are also produced by the MPO-H2O2-C1- system.", "contents": "Chlorination, decarboxylation and bactericidal activity mediated by the MPO-H2O2-C1- system. 1. MPO, H2O2 and C1- form a complex that undergoes intramolecular rearrangement yielding the chlorinium ion. 2. The chlorinium ion can interact with MPO, bacteria and amino acids. 3. The reaction can occur at a wide range of pH, H2O2 concentration and C1- concentration. 4. The chlorinium ion can attack different protein molecules to cause structural changes. 5. Preincubation of MPO with bacteria results in greater bactericidal activity. 6. Diffusible bactericidal agents are also produced by the MPO-H2O2-C1- system."}
{"id": "PMID:11650", "title": "Antagonism of arachidonic acid hydroperoxide on isolated gastrointestinal tissues as a measure of the inhibition of prostaglandin biosynthesis.", "content": "Arachidonic acid hydroperoxide (AAP)-induced contractions of the isolated guinea pig ileum and rat stomach fundus are inhibited by suprofen [alpha-methyl-4-(2-thienylcarbonyl) benzeneacetic acid], indomethacin, phenylbutazone, and acetylsalicyclic acid in descending order of activity. This effect is highly specific, since prostaglandins (PG) and various agonists of gastrointestinal smooth muscle are not, or only weakly antagonized by these four compounds, whereas various compounds, including narcotic analgesics, are inactive versus AAP. The antagonism of AAP-induced contractions of the isolated rat stomach fundus is a valuable test system for inhibitors of PG biosynthesis.", "contents": "Antagonism of arachidonic acid hydroperoxide on isolated gastrointestinal tissues as a measure of the inhibition of prostaglandin biosynthesis. Arachidonic acid hydroperoxide (AAP)-induced contractions of the isolated guinea pig ileum and rat stomach fundus are inhibited by suprofen [alpha-methyl-4-(2-thienylcarbonyl) benzeneacetic acid], indomethacin, phenylbutazone, and acetylsalicyclic acid in descending order of activity. This effect is highly specific, since prostaglandins (PG) and various agonists of gastrointestinal smooth muscle are not, or only weakly antagonized by these four compounds, whereas various compounds, including narcotic analgesics, are inactive versus AAP. The antagonism of AAP-induced contractions of the isolated rat stomach fundus is a valuable test system for inhibitors of PG biosynthesis."}
{"id": "PMID:11654", "title": "Splenomegaly in Northern Nigeria.", "content": "Seventy five patients with large spleens were investigated in order to establish the causes of splenomegaly in Northern Nigeria, to define further the diagnostic criteria of tropical splenomegaly syndrome (TSS), and to study its pathogenesis. Investigations included examination of liver biopsy, bone marrow cytology, lymphocyte response to phytohaemagglutinin (PHA), serum immunoglobulins and complement, and the presence of immunoglobulin and complement fixed in Kupffer cells. Thirty patients had TSS, five chronic lymphatic leukaemia (CLL), four a syndrome of gross lymphoid hyperplasia (GLH) distinct from TSS, CLL and the lymphomas, and twenty three miscellaneous conventional diseases. In thirteen cases no definite diagnosis could be established. TSS was found to be predominantly a disease of female Fulani cattle herders. Its essential characteristics were splenomegaly in the presence of acquired immunity to malaria, a grossly raised serum IgM, a lowered serum complement, and the presence of IgM fixed in Kupffer cells. There was lymphoid hyperplasia in bone marrow, hepatic sinusoids and often blood which may be indistinguishable from that in CLL. Lymphocytes undergo normal blastogenesis to PHA. There was clinical and haematological response to proguanil therapy. Reticuloendothelial phagocytosis of IgM, probably as a complex, seems to be the essential feature of the condition. As it was impossible to identify early cases of TSS it is unclear whether IgM overproduction or phagocytosis of IgM complexes is the first stage of the disease. The precise nature of the association with malaria remains obscure. The diagnosis of CLL demanded the demonstration of an abnormally low immunoglobulin level and impaired lymphocyte responsiveness to PHA by blast transformation or 3H-thymidine incorporation, in addition to the usual haematological findings. The syndrome GLH occurred in multiparous Hausa women. It was characterised by intense lymphocytosis with active, PHA-responsive cells, and normal immunoglobulin levels. Patients responded to proguanil therapy. It is suggested that these patients have a depressed immune response to malaria, perhaps through repeated pregnancies, and to a leukaemogenic agent, both of which stimulate lymphocytosis. Antimalarial treatment at this stage may prevent the development of frank leukaemia or lymphoma. The usefulness of the various investigative procedures and the problem of managing the large number of undiagnosed cases are discussed.", "contents": "Splenomegaly in Northern Nigeria. Seventy five patients with large spleens were investigated in order to establish the causes of splenomegaly in Northern Nigeria, to define further the diagnostic criteria of tropical splenomegaly syndrome (TSS), and to study its pathogenesis. Investigations included examination of liver biopsy, bone marrow cytology, lymphocyte response to phytohaemagglutinin (PHA), serum immunoglobulins and complement, and the presence of immunoglobulin and complement fixed in Kupffer cells. Thirty patients had TSS, five chronic lymphatic leukaemia (CLL), four a syndrome of gross lymphoid hyperplasia (GLH) distinct from TSS, CLL and the lymphomas, and twenty three miscellaneous conventional diseases. In thirteen cases no definite diagnosis could be established. TSS was found to be predominantly a disease of female Fulani cattle herders. Its essential characteristics were splenomegaly in the presence of acquired immunity to malaria, a grossly raised serum IgM, a lowered serum complement, and the presence of IgM fixed in Kupffer cells. There was lymphoid hyperplasia in bone marrow, hepatic sinusoids and often blood which may be indistinguishable from that in CLL. Lymphocytes undergo normal blastogenesis to PHA. There was clinical and haematological response to proguanil therapy. Reticuloendothelial phagocytosis of IgM, probably as a complex, seems to be the essential feature of the condition. As it was impossible to identify early cases of TSS it is unclear whether IgM overproduction or phagocytosis of IgM complexes is the first stage of the disease. The precise nature of the association with malaria remains obscure. The diagnosis of CLL demanded the demonstration of an abnormally low immunoglobulin level and impaired lymphocyte responsiveness to PHA by blast transformation or 3H-thymidine incorporation, in addition to the usual haematological findings. The syndrome GLH occurred in multiparous Hausa women. It was characterised by intense lymphocytosis with active, PHA-responsive cells, and normal immunoglobulin levels. Patients responded to proguanil therapy. It is suggested that these patients have a depressed immune response to malaria, perhaps through repeated pregnancies, and to a leukaemogenic agent, both of which stimulate lymphocytosis. Antimalarial treatment at this stage may prevent the development of frank leukaemia or lymphoma. The usefulness of the various investigative procedures and the problem of managing the large number of undiagnosed cases are discussed."}
{"id": "PMID:11655", "title": "Rheumatic fever and rheumatic heart disease among 56,8000 inhabitants in southeast Teheran from 1972-1974.", "content": "A study of the incidence of R. fever in an area in southeast Teheran during the period 1972-1974 revealed 92 cases. The crude annual incidence of R. fever ranged from a high of 58 cases to a low of 51 cases per 100,000 population. The age and sex specific rates revealed the incidence to be strikingly higher in the 5-19 year age group, reaching roughly 80/100,000. There was an approximately similar number of males and females with R. fever. Among the R. fever patients, there were 6 cases of chorea, 5 girls and 1 boy. From 92 R. fever cases, 49 (53%) developed carditis. Among these patients, 35 (71%) were female in contrast to 14 (29%) male cases. Overall there were 59 cases (62%) which were initial attacks and 33 cases (38%) which were recurrences. During the trial there were also 7 recurrences of R fever and 4 deaths. The seasonal pattern showed that the majority of cases occurred during the winter and spring months. From the R. fever/R.H.D. patients, 63 (70%) and from cases with carditis alone, 24 (40%) were hospitalized.", "contents": "Rheumatic fever and rheumatic heart disease among 56,8000 inhabitants in southeast Teheran from 1972-1974. A study of the incidence of R. fever in an area in southeast Teheran during the period 1972-1974 revealed 92 cases. The crude annual incidence of R. fever ranged from a high of 58 cases to a low of 51 cases per 100,000 population. The age and sex specific rates revealed the incidence to be strikingly higher in the 5-19 year age group, reaching roughly 80/100,000. There was an approximately similar number of males and females with R. fever. Among the R. fever patients, there were 6 cases of chorea, 5 girls and 1 boy. From 92 R. fever cases, 49 (53%) developed carditis. Among these patients, 35 (71%) were female in contrast to 14 (29%) male cases. Overall there were 59 cases (62%) which were initial attacks and 33 cases (38%) which were recurrences. During the trial there were also 7 recurrences of R fever and 4 deaths. The seasonal pattern showed that the majority of cases occurred during the winter and spring months. From the R. fever/R.H.D. patients, 63 (70%) and from cases with carditis alone, 24 (40%) were hospitalized."}
{"id": "PMID:11656", "title": "Incidence of and beliefs about trypanosomiasis in the Senegal River Basin.", "content": "A survey was conducted for trypanosomiasis of 10,875 persons living in 56 villages in the Senegal River Basin in Mali. The incidence of the disease was found to be 137.9/100,000. An interview survey was simultaneously undertaken in order to elucidate local beliefs about the disease. Although trypanosomiasis is recognized as a distinct disease entity once the late stage has developed, there is no knowledge of its relationship to tsetse flies. It is common knowledge that hunters who frequent riverine forest galleries and forested savanna often contract the disease. Their frequent and intense exposure to Glossina sp. is not viewed as having any relationship to their contracting the disease.", "contents": "Incidence of and beliefs about trypanosomiasis in the Senegal River Basin. A survey was conducted for trypanosomiasis of 10,875 persons living in 56 villages in the Senegal River Basin in Mali. The incidence of the disease was found to be 137.9/100,000. An interview survey was simultaneously undertaken in order to elucidate local beliefs about the disease. Although trypanosomiasis is recognized as a distinct disease entity once the late stage has developed, there is no knowledge of its relationship to tsetse flies. It is common knowledge that hunters who frequent riverine forest galleries and forested savanna often contract the disease. Their frequent and intense exposure to Glossina sp. is not viewed as having any relationship to their contracting the disease."}
{"id": "PMID:11657", "title": "[Toxoplasmosis in the Republic of Mali. An epidemiologic approach].", "content": "1664- sera from children and adults were collected in rural and urban areas of Mali and were tested in Toxoplasmosis serology. Immunofluorescent antibody tests and direct agglutination test have been used for this purpose. 65 per cent of adults from urban area and 56 to 58 per cent of adults from rural area gave positive results. Before the age sixteen, only 33 to 40 percent of children are positive in urban area while 51 to 53 per cent are so in rural area. The study of hundreds of sera collected from various animals allows to explain the different ages of the serological changes. In rural area children have been infected very early after catching birds, reptiles and above all, rodents and eating them not cooked enough. In urban area the infection occurs all along the life and, particularly, in adults, after consuming grilled meat. The recent description of three cases of congenital toxoplasmosis demonstrates the interest of such an epidemiological study.", "contents": "[Toxoplasmosis in the Republic of Mali. An epidemiologic approach]. 1664- sera from children and adults were collected in rural and urban areas of Mali and were tested in Toxoplasmosis serology. Immunofluorescent antibody tests and direct agglutination test have been used for this purpose. 65 per cent of adults from urban area and 56 to 58 per cent of adults from rural area gave positive results. Before the age sixteen, only 33 to 40 percent of children are positive in urban area while 51 to 53 per cent are so in rural area. The study of hundreds of sera collected from various animals allows to explain the different ages of the serological changes. In rural area children have been infected very early after catching birds, reptiles and above all, rodents and eating them not cooked enough. In urban area the infection occurs all along the life and, particularly, in adults, after consuming grilled meat. The recent description of three cases of congenital toxoplasmosis demonstrates the interest of such an epidemiological study."}
{"id": "PMID:11658", "title": "[Changes in the blood pictureof the red goat of Maradi as a function of its gastrointestinal parasitism].", "content": "Numerous \"ch\u00e8vres de Maradi\" are bred in Republique du Niger (cap. Niamey), 2 - 10(+6) numbered in 1973. This rustic ruminant is often very parasitized by intestinal nematodes and sporozoa. The most frequent genera are Bunostomum (55%), Trichostrongylus (40%), Strongyloides (27%), Oesophagostomum and Haemonchus (20%), sometimes Moniezia or Stilesia, coccidiosis being endemic and very pathogenic, Eimeria (70%). Polyparasitism is a \"modus vivendi\" between the host and these various parasites. All modification of the number or the kind of parasites (prevalence of one or two genera) involves a variation of the differential leucocyte count (anthelmintic cure for example). When the normal leucocyte count is 18 to 22 - 10(+3) per mm3, whose neutrophils: 40.73%; acidophils: 2%; basophils: 0.28%; monocytes: 11.28%; lymphocytes (small and big forms): 45.71%, a tapeworm parasitism by adults (Moniezia or Stilesia) or by peritoneal larvae (Cysticercus sp.) involves a light eosinophilia (8%), in morbid cases of coccidiosis, neutrophilia prevails (70%), and a polyparasitism with nematodes and Eimeria is characterized by monocytosis and neutrophilia, the polynuclear eosinophils being very rare. These observations show the necessity to elaborate simultaneously two cures: the first with an anthelmintic product, the second against coccidia, to avoid an uncertain Eimeria proliferation after the nematode destruction. In African breeding conditions, where polyparasitism is very frequent, such a therapeutic schedule is recommended.", "contents": "[Changes in the blood pictureof the red goat of Maradi as a function of its gastrointestinal parasitism]. Numerous \"ch\u00e8vres de Maradi\" are bred in Republique du Niger (cap. Niamey), 2 - 10(+6) numbered in 1973. This rustic ruminant is often very parasitized by intestinal nematodes and sporozoa. The most frequent genera are Bunostomum (55%), Trichostrongylus (40%), Strongyloides (27%), Oesophagostomum and Haemonchus (20%), sometimes Moniezia or Stilesia, coccidiosis being endemic and very pathogenic, Eimeria (70%). Polyparasitism is a \"modus vivendi\" between the host and these various parasites. All modification of the number or the kind of parasites (prevalence of one or two genera) involves a variation of the differential leucocyte count (anthelmintic cure for example). When the normal leucocyte count is 18 to 22 - 10(+3) per mm3, whose neutrophils: 40.73%; acidophils: 2%; basophils: 0.28%; monocytes: 11.28%; lymphocytes (small and big forms): 45.71%, a tapeworm parasitism by adults (Moniezia or Stilesia) or by peritoneal larvae (Cysticercus sp.) involves a light eosinophilia (8%), in morbid cases of coccidiosis, neutrophilia prevails (70%), and a polyparasitism with nematodes and Eimeria is characterized by monocytosis and neutrophilia, the polynuclear eosinophils being very rare. These observations show the necessity to elaborate simultaneously two cures: the first with an anthelmintic product, the second against coccidia, to avoid an uncertain Eimeria proliferation after the nematode destruction. In African breeding conditions, where polyparasitism is very frequent, such a therapeutic schedule is recommended."}
{"id": "PMID:11660", "title": "[Distribution and ecology of Ixodes trianguliceps (Birula, 1895) (Acarina, Ixodoidea) in France, particularly in the South-East].", "content": "Ixodes trianguliceps, parasite of insectivores and rodent mammals seems to be distributed throughout France, except in the mediterranean low altitude areas. This tick which does not manifest any parasitic specificty, has meanwhile preferred hosts (Clethrionomys glareolus, especially). At low altitudes, it likes forests, hedge-rows and heaths and at higher altitudes (Subalpine and alpine), opened area may be densely inhabited. The authors study the numerous concerned vegetal associations and precise the tick's phenology, particularly in the Bas-Dauphin\u00e9. They also discuss the many hypothesis concerning the still unknown ecology of I. trianguliceps free instars.", "contents": "[Distribution and ecology of Ixodes trianguliceps (Birula, 1895) (Acarina, Ixodoidea) in France, particularly in the South-East]. Ixodes trianguliceps, parasite of insectivores and rodent mammals seems to be distributed throughout France, except in the mediterranean low altitude areas. This tick which does not manifest any parasitic specificty, has meanwhile preferred hosts (Clethrionomys glareolus, especially). At low altitudes, it likes forests, hedge-rows and heaths and at higher altitudes (Subalpine and alpine), opened area may be densely inhabited. The authors study the numerous concerned vegetal associations and precise the tick's phenology, particularly in the Bas-Dauphin\u00e9. They also discuss the many hypothesis concerning the still unknown ecology of I. trianguliceps free instars."}
{"id": "PMID:11662", "title": "Buoyant density of some togaviruses in sucrose density gradient and capacity of their haemagglutinin fractions to interact with antibody.", "content": "The buoyant densities of Western equine encephalomyelitis virus (an Alphavirus) and tick-borne encephalitis (TBE) virus (a Flavivirus) antigens prepared by different methods were studied. Sucrose density centrifugation revealed a heterogeneity in the density of the virions. The sedimentation pattern and height of peaks of the haemagglutinating activities and infectivity, other conditions being equal, depended both on the virus species and properties of its strains and on the mode of preparation and treatment of the virus-containing material. Different haemagglutinating antigen fractions differed in their capacity to interact with specific antibody. It was suggested that the kinetics of a serological reaction and its result depend on the functional activity of the antigen preparation and, in particular, on the proportion in the reaction mixture of virus particles with a dissimilar antigenic structure.", "contents": "Buoyant density of some togaviruses in sucrose density gradient and capacity of their haemagglutinin fractions to interact with antibody. The buoyant densities of Western equine encephalomyelitis virus (an Alphavirus) and tick-borne encephalitis (TBE) virus (a Flavivirus) antigens prepared by different methods were studied. Sucrose density centrifugation revealed a heterogeneity in the density of the virions. The sedimentation pattern and height of peaks of the haemagglutinating activities and infectivity, other conditions being equal, depended both on the virus species and properties of its strains and on the mode of preparation and treatment of the virus-containing material. Different haemagglutinating antigen fractions differed in their capacity to interact with specific antibody. It was suggested that the kinetics of a serological reaction and its result depend on the functional activity of the antigen preparation and, in particular, on the proportion in the reaction mixture of virus particles with a dissimilar antigenic structure."}
{"id": "PMID:11663", "title": "The opposite temperature-sensitivity character (ts) in two attenuated flaviviruses, used for human immunization: 17D yellow fever and E5\"14\" (Langat) viruses. A reappraisal of thoughts.", "content": "For the reproduction of the man-attenuated E5\"14\" clone of the Langat virus (tick-borne encephalitis complex) in pig kidney epithelial cells, the temperature of 39 degrees C was shown as restrictive, whereas it was permissive for the 17D strain of yellow fever virus and three virulent strains of tick-borne encephalitis (western subtype) virus. The temperature of 36 degrees C permitted the reproduction of all viruses studied. The implication of genetic marker studies in the assessment of human neuropathogenicity of flaviviruses is discussed.", "contents": "The opposite temperature-sensitivity character (ts) in two attenuated flaviviruses, used for human immunization: 17D yellow fever and E5\"14\" (Langat) viruses. A reappraisal of thoughts. For the reproduction of the man-attenuated E5\"14\" clone of the Langat virus (tick-borne encephalitis complex) in pig kidney epithelial cells, the temperature of 39 degrees C was shown as restrictive, whereas it was permissive for the 17D strain of yellow fever virus and three virulent strains of tick-borne encephalitis (western subtype) virus. The temperature of 36 degrees C permitted the reproduction of all viruses studied. The implication of genetic marker studies in the assessment of human neuropathogenicity of flaviviruses is discussed."}
{"id": "PMID:11664", "title": "Studies on the characteristics of Poliovirus type 3. III. Strain characteristics after passage in man.", "content": "The markers d, IST, EA1(OH)3 and rct at sub- and supraoptimal temperatures as well as neurovirulence (PMic) for monkeys was determined for strains isolated from children vaccinated with Leon 12a1b vaccine, their contacts and from paralytic cases. The strains were isolated at early and late phases of excretion. The changes concerned mainly rct determined at supraoptimal temperatures, d and PMic markers, especially in strains isolated at the late phase of excretion. The passage through the human alimentary tract did not change such markers as IST and EA1(OH)3. Some degree of correlation was observed between the rct 40.3, d and PMic markers.", "contents": "Studies on the characteristics of Poliovirus type 3. III. Strain characteristics after passage in man. The markers d, IST, EA1(OH)3 and rct at sub- and supraoptimal temperatures as well as neurovirulence (PMic) for monkeys was determined for strains isolated from children vaccinated with Leon 12a1b vaccine, their contacts and from paralytic cases. The strains were isolated at early and late phases of excretion. The changes concerned mainly rct determined at supraoptimal temperatures, d and PMic markers, especially in strains isolated at the late phase of excretion. The passage through the human alimentary tract did not change such markers as IST and EA1(OH)3. Some degree of correlation was observed between the rct 40.3, d and PMic markers."}
{"id": "PMID:11665", "title": "Effect of methyl glyoxal on infectivity and antigenicity of foot-and-mouth disease virus.", "content": "The inactivating effect of methyl glyoxal on foot-and-mouth disease (FMD) virus was studied. The rate of inactivation depended upon the drug concentration, incubation temperature and pH of the medium. RNA recovered from the inactivated virus was not infectious. The complement-fixing activity of the virus was not reduced by methyl glyoxal treatment. The antigenicity of inactivated virus preparations determined by levels of virus neutralizing antibody in the blood sera of immunized white rats and rabbits was not inferior to that of the initial uninactivated virus.", "contents": "Effect of methyl glyoxal on infectivity and antigenicity of foot-and-mouth disease virus. The inactivating effect of methyl glyoxal on foot-and-mouth disease (FMD) virus was studied. The rate of inactivation depended upon the drug concentration, incubation temperature and pH of the medium. RNA recovered from the inactivated virus was not infectious. The complement-fixing activity of the virus was not reduced by methyl glyoxal treatment. The antigenicity of inactivated virus preparations determined by levels of virus neutralizing antibody in the blood sera of immunized white rats and rabbits was not inferior to that of the initial uninactivated virus."}
{"id": "PMID:11666", "title": "Some immunological mechanisms of the influenza virus antitumour effect.", "content": "Vaccine strains of influenza A virus inhibited the growth of ascitic tumour cells and outbred rats or inbred mice. The infected tumour bearers had an enhanced immune response to viral and specific tumour antigens. These phenomena are apparently due to the formation of complexes of both antigens on cell membranes and increased immunogenicity of such complexes.", "contents": "Some immunological mechanisms of the influenza virus antitumour effect. Vaccine strains of influenza A virus inhibited the growth of ascitic tumour cells and outbred rats or inbred mice. The infected tumour bearers had an enhanced immune response to viral and specific tumour antigens. These phenomena are apparently due to the formation of complexes of both antigens on cell membranes and increased immunogenicity of such complexes."}
{"id": "PMID:11667", "title": "In vitro studies on cell-mediated immune response to tick-borne encephalitis virus: findings in convalescents and human subclinical infections.", "content": "Peripheral blood leukocytes from tick-borne encephalitis (TBE) convelescents (manifest and inapparent forms) working with TBE virus-containing material and from individuals without specific serum virus neutralizing antibodies (VNA) were studied in capillary tube leukocyte migration experiments. Partially purified TBE virus preparations were used as antigen. Under standardized conditions a strong inhibitory reaction was observed in convalescents with significantly higher values in persons recovered from an abortive form of infection only. These results differed markedly from values recorded in persons without specific VNA. Significance of correlation between humoral VNA titres and the intensity of the cell-mediated component of the immune response (CM IR), as indicated by leukocyte migration inhibition (LMI) values, was less than P equals 0.25.", "contents": "In vitro studies on cell-mediated immune response to tick-borne encephalitis virus: findings in convalescents and human subclinical infections. Peripheral blood leukocytes from tick-borne encephalitis (TBE) convelescents (manifest and inapparent forms) working with TBE virus-containing material and from individuals without specific serum virus neutralizing antibodies (VNA) were studied in capillary tube leukocyte migration experiments. Partially purified TBE virus preparations were used as antigen. Under standardized conditions a strong inhibitory reaction was observed in convalescents with significantly higher values in persons recovered from an abortive form of infection only. These results differed markedly from values recorded in persons without specific VNA. Significance of correlation between humoral VNA titres and the intensity of the cell-mediated component of the immune response (CM IR), as indicated by leukocyte migration inhibition (LMI) values, was less than P equals 0.25."}
{"id": "PMID:11668", "title": "Computer evaluation of antiviral activities of some thiosemicarbazones in experiments in vivo.", "content": "A new mathematical method based on 3-, 4- or 6-point parallel-line assays was applied for working out a computer programme used to evaluate the activity of some new isatin-beta-thiosemicarbazone derivatives against vaccinia virus, studied in vivo.", "contents": "Computer evaluation of antiviral activities of some thiosemicarbazones in experiments in vivo. A new mathematical method based on 3-, 4- or 6-point parallel-line assays was applied for working out a computer programme used to evaluate the activity of some new isatin-beta-thiosemicarbazone derivatives against vaccinia virus, studied in vivo."}
{"id": "PMID:11669", "title": "Quantitative assay of influenza virus soluble antigen by complement-fixation micromethod.", "content": "A modified micromethod of complement fixation (CF) reaction for quantitive assay of Influenzavirus soluble (s) antigen was elaborated. The method makes it possible to determine microquantities of s-antigen with an accuracy of +/- 15%. The accuracy of the method was checked by theoretical calculations.", "contents": "Quantitative assay of influenza virus soluble antigen by complement-fixation micromethod. A modified micromethod of complement fixation (CF) reaction for quantitive assay of Influenzavirus soluble (s) antigen was elaborated. The method makes it possible to determine microquantities of s-antigen with an accuracy of +/- 15%. The accuracy of the method was checked by theoretical calculations."}
{"id": "PMID:11670", "title": "Stable erythrocyte diagnostic preparation for passive haemagglutination test with herpes simplex virus antigen.", "content": "A method for the preparation of stable suspensions of erythrocytes sensitized with herpes simplex virus (HSV) antigen and for their use in the passive haemagglutination test (PHAT) was developed. Formolized sheep erythrocytes were treated with tannin and sensitized with HSV antigen prepared from infected chick embryo cell culture by ultrasonication and virus extraction with alkaline glycine buffer. Antibody titres determined in the PHAT were higher than titres of neutralizing antibody. The specificity of the results was checked by the passive haemagglutination-inhibition test (PHAIT). The sensitized erythrocytes retained their activity for 5 months (the observation period) and gave reproducible results. The availability of stable erythrocyte diagnostic preparations simplifies the detection of herpesvirus antibody and makes the method widely applicable.", "contents": "Stable erythrocyte diagnostic preparation for passive haemagglutination test with herpes simplex virus antigen. A method for the preparation of stable suspensions of erythrocytes sensitized with herpes simplex virus (HSV) antigen and for their use in the passive haemagglutination test (PHAT) was developed. Formolized sheep erythrocytes were treated with tannin and sensitized with HSV antigen prepared from infected chick embryo cell culture by ultrasonication and virus extraction with alkaline glycine buffer. Antibody titres determined in the PHAT were higher than titres of neutralizing antibody. The specificity of the results was checked by the passive haemagglutination-inhibition test (PHAIT). The sensitized erythrocytes retained their activity for 5 months (the observation period) and gave reproducible results. The availability of stable erythrocyte diagnostic preparations simplifies the detection of herpesvirus antibody and makes the method widely applicable."}
{"id": "PMID:11673", "title": "Uptake of labelled tobacco mosaic virus by tobacco protoplasts in the presence of metabolic inhibitors and at low temperature.", "content": "In the presence of inhibitors of protein synthesis and energy metabolism, tobacco protoplasts were shown to retain 14C-labelled tobacco mosaic virus (14C-TMV) with the same intensity as in control. At 2 degrees C, the protoplasts retained 14C-TMV at approximately the same rate as at 25 degrees C. In protoplasts inocculated at different temperatures, approximately equal amounts of infectious virus were produced, this being possibly indicative of a non-physiological nature of the first stages of virus penetration into the protoplast.", "contents": "Uptake of labelled tobacco mosaic virus by tobacco protoplasts in the presence of metabolic inhibitors and at low temperature. In the presence of inhibitors of protein synthesis and energy metabolism, tobacco protoplasts were shown to retain 14C-labelled tobacco mosaic virus (14C-TMV) with the same intensity as in control. At 2 degrees C, the protoplasts retained 14C-TMV at approximately the same rate as at 25 degrees C. In protoplasts inocculated at different temperatures, approximately equal amounts of infectious virus were produced, this being possibly indicative of a non-physiological nature of the first stages of virus penetration into the protoplast."}
{"id": "PMID:11680", "title": "Present state of alpha and beta adrenergic drugs. II. The adrenergic blocking agents.", "content": "There are selective blocking agents (antagonists) for alpha receptors and beta receptors. These blocking agents prevent the response to injected agonists and neurogenically released norepinephrine. The principal cardiovascular response to alpha blockade is postural hypotension with reflexly induced cardiac stimulation. If neurogenic vasoconstriction is present, this will be removed. The principal cardiovascular response to beta blockade is bradycardia. If fast arrhythmias are present, these will be slowed. Beta blockade tends to increase peripheral resistance. Unless circulation is previously impaired this vasoconstrictive effect is insignificant.", "contents": "Present state of alpha and beta adrenergic drugs. II. The adrenergic blocking agents. There are selective blocking agents (antagonists) for alpha receptors and beta receptors. These blocking agents prevent the response to injected agonists and neurogenically released norepinephrine. The principal cardiovascular response to alpha blockade is postural hypotension with reflexly induced cardiac stimulation. If neurogenic vasoconstriction is present, this will be removed. The principal cardiovascular response to beta blockade is bradycardia. If fast arrhythmias are present, these will be slowed. Beta blockade tends to increase peripheral resistance. Unless circulation is previously impaired this vasoconstrictive effect is insignificant."}
{"id": "PMID:11682", "title": "The binding of the components of mixed micelle to dietary fiber.", "content": "Bile acid conjugates are adsorbed to cereal fiber. Bile acid conjugates incorporated into micelles with cholesterol are reversibly adsorbed as micelles on to the fiber. Incorporating bile acid conjugates into micelles with monoglycerides somewhat depresses adsorption of bile acid conjugate. If fatty acids, monoglycerides, and bile acid conjugate mixed micelles are exposed to cereal fiber, then adsorption of bile acids to the fiber is diminished. The extent to which the adsorption is diminished is affected by the fatty acid concentration, chain length, and unsaturation. This suggests that bile acid conjugates are minimally adsorbed to fiber in the jejunum but deconjugation and dehydroxylation as in the cecum favors adsorption.", "contents": "The binding of the components of mixed micelle to dietary fiber. Bile acid conjugates are adsorbed to cereal fiber. Bile acid conjugates incorporated into micelles with cholesterol are reversibly adsorbed as micelles on to the fiber. Incorporating bile acid conjugates into micelles with monoglycerides somewhat depresses adsorption of bile acid conjugate. If fatty acids, monoglycerides, and bile acid conjugate mixed micelles are exposed to cereal fiber, then adsorption of bile acids to the fiber is diminished. The extent to which the adsorption is diminished is affected by the fatty acid concentration, chain length, and unsaturation. This suggests that bile acid conjugates are minimally adsorbed to fiber in the jejunum but deconjugation and dehydroxylation as in the cecum favors adsorption."}
{"id": "PMID:11683", "title": "Anti-inflammatory drug treatment in Crohn's disease.", "content": "In a prospective evaluation of all patients with Crohn's disease treated by us since 1970, 62 have completed at least one year, or required bowel resection after at least three months, of anti-inflammatory drug treatment. Sulfasalazine alone was used in 24 patients, steroids alone were used in four patients, both drugs were used together in 29 patients and azathioprine was added to the drug regimen of five patients. The initial choice of drug followed a set design but the regimens ultimately arrived at depended upon patient responses. Favorable complete or partial clinical responses were obtained in 54 patients, while 37 patients showed objective radiographic improvement or regression. No radiographic improvement was found in the eight patients with clinical treatment failure as well as in 11 patients with clinical improvement. Six clinically improved patients had not yet been re-examined radiographically. The study provides objective evidence that the majority of patients with Crohn's disease can be successfully treated by means of anti-inflammatory drugs.", "contents": "Anti-inflammatory drug treatment in Crohn's disease. In a prospective evaluation of all patients with Crohn's disease treated by us since 1970, 62 have completed at least one year, or required bowel resection after at least three months, of anti-inflammatory drug treatment. Sulfasalazine alone was used in 24 patients, steroids alone were used in four patients, both drugs were used together in 29 patients and azathioprine was added to the drug regimen of five patients. The initial choice of drug followed a set design but the regimens ultimately arrived at depended upon patient responses. Favorable complete or partial clinical responses were obtained in 54 patients, while 37 patients showed objective radiographic improvement or regression. No radiographic improvement was found in the eight patients with clinical treatment failure as well as in 11 patients with clinical improvement. Six clinically improved patients had not yet been re-examined radiographically. The study provides objective evidence that the majority of patients with Crohn's disease can be successfully treated by means of anti-inflammatory drugs."}
{"id": "PMID:11684", "title": "A filtration model for study of leukocyte transit in the microcirculation.", "content": "In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes.", "contents": "A filtration model for study of leukocyte transit in the microcirculation. In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes."}
{"id": "PMID:11685", "title": "Pharmacology and therapeutic use of antihistamines.", "content": "The classes of antihistaminic agents, their pharmacology and therapeutic uses, adverse effects, drug interactions, toxic overdoses and abuse are reviewed. It is concluded that antihistamines are valuable drugs for treating a number of conditions and diseases (e.g. allergic rhinitis, motion sickness and parkinsonism), but proof of efficacy has not been established for the treatment of cardiac arrhythmias, peptic ulcers, insomnia and headaches. Because responses to antihistamines may vary, titration of each patient's dose is recommended.", "contents": "Pharmacology and therapeutic use of antihistamines. The classes of antihistaminic agents, their pharmacology and therapeutic uses, adverse effects, drug interactions, toxic overdoses and abuse are reviewed. It is concluded that antihistamines are valuable drugs for treating a number of conditions and diseases (e.g. allergic rhinitis, motion sickness and parkinsonism), but proof of efficacy has not been established for the treatment of cardiac arrhythmias, peptic ulcers, insomnia and headaches. Because responses to antihistamines may vary, titration of each patient's dose is recommended."}
{"id": "PMID:11686", "title": "Hemolysis of erythrocytes by primary pharmacologic agents, part 2: influence of the vehicle.", "content": "The hemolytic activity in vitro of chlorpromazine hydrochloride, chlordiazepoxide hydrochloride and brompheniramine maleate was examined using various intravenous solutions as the vehicle. Fresh human blood was employed in the investigation which used a colorimetric method for the determination of hemolysis. Prior to the examination of the hemolytic activity of each drug in the various vehicles, the vehicles themselves were examined for their ability to protect erythrocytes from hemolysis. Little to no hemolysis occurred in normal saline solution (the standard), dextrose 2.5% in normal saline, dextrose 5% in normal saline, dextrose 10% in normal saline, and lactated Ringer's injection. Low levels of hemolysis occurred in dextrose 5% in water, invert sugar 10% in water, and M/6 sodium lactate in water. High levels of hemolysis occurred when red blood cells were suspended in dextrose 2.5% in water. Invert sugar 10% in normal saline and fructose 10% in water caused red cell denaturation resulting in brown cells and hemolysate rather than the characteristic red color. This denaturation was attributed to the hydrogen ion concentration of these two solutions, both having pH values less than 4.0. Vehicles of dextrose in saline, dextrose in water, lactated Ringer's, and invert sugar in water reduced the level of drug-induced hemolysis for the drugs tested compared to that which occurred in normal saline solution. The reduction of hemolysis was greater as the tonicity of the vehicle used was increased. It was concluded that the pharmaceutical vehicles examined have an influence on the cellular effects of drugs which only affects the erythrocyte but which could potentially affect the drugs' distribution from the blood to the sites of their action.", "contents": "Hemolysis of erythrocytes by primary pharmacologic agents, part 2: influence of the vehicle. The hemolytic activity in vitro of chlorpromazine hydrochloride, chlordiazepoxide hydrochloride and brompheniramine maleate was examined using various intravenous solutions as the vehicle. Fresh human blood was employed in the investigation which used a colorimetric method for the determination of hemolysis. Prior to the examination of the hemolytic activity of each drug in the various vehicles, the vehicles themselves were examined for their ability to protect erythrocytes from hemolysis. Little to no hemolysis occurred in normal saline solution (the standard), dextrose 2.5% in normal saline, dextrose 5% in normal saline, dextrose 10% in normal saline, and lactated Ringer's injection. Low levels of hemolysis occurred in dextrose 5% in water, invert sugar 10% in water, and M/6 sodium lactate in water. High levels of hemolysis occurred when red blood cells were suspended in dextrose 2.5% in water. Invert sugar 10% in normal saline and fructose 10% in water caused red cell denaturation resulting in brown cells and hemolysate rather than the characteristic red color. This denaturation was attributed to the hydrogen ion concentration of these two solutions, both having pH values less than 4.0. Vehicles of dextrose in saline, dextrose in water, lactated Ringer's, and invert sugar in water reduced the level of drug-induced hemolysis for the drugs tested compared to that which occurred in normal saline solution. The reduction of hemolysis was greater as the tonicity of the vehicle used was increased. It was concluded that the pharmaceutical vehicles examined have an influence on the cellular effects of drugs which only affects the erythrocyte but which could potentially affect the drugs' distribution from the blood to the sites of their action."}
{"id": "PMID:11687", "title": "Beta blockers in hypertension: a review.", "content": "The mechanisms of action, clinical use and untoward reactions of the beta-adrenergic blocking drugs, with particular attention to the role of these agents in the treatment of hypertension, are reviewed. Specific topics covered include the effect of beta-adrenergic blockade on the heart, renin secretion and the central nervous system; the efficacy and pharmacokinetics of beta-blocking agents; combinations with other drugs; patient acceptance and advantages; and toxicity and side effects. It is concluded that, with proper dosage titration, most hypertensive patients could probably be controlled on beta blockers alone or in combination with a diuretic.", "contents": "Beta blockers in hypertension: a review. The mechanisms of action, clinical use and untoward reactions of the beta-adrenergic blocking drugs, with particular attention to the role of these agents in the treatment of hypertension, are reviewed. Specific topics covered include the effect of beta-adrenergic blockade on the heart, renin secretion and the central nervous system; the efficacy and pharmacokinetics of beta-blocking agents; combinations with other drugs; patient acceptance and advantages; and toxicity and side effects. It is concluded that, with proper dosage titration, most hypertensive patients could probably be controlled on beta blockers alone or in combination with a diuretic."}
{"id": "PMID:11688", "title": "Effect of orange juice consumption on urinary pH.", "content": "The effect of orange juice consumption on urinary pH was studied in seven adult male subjects, each of whom served as his own control. The diet of the subjects was standardized during the work-day. The effects of two regimens of orange juice were studied: 1500 ml divided into five 300-ml portions during the day, and 300 ml once in the morning. Urine was collected, its pH recorded, and titrated with HCl to determine the mEq of base excreted per unit time. The consumption of 300 ml of orange juice did not significantly alter urinary pH. The consumption of 1500 of orange juice changed the urinary pH by an average of one pH unit. A change of this magnitude could cause clinically significant variation in the overall excretion pattern of acidic or basic drugs.", "contents": "Effect of orange juice consumption on urinary pH. The effect of orange juice consumption on urinary pH was studied in seven adult male subjects, each of whom served as his own control. The diet of the subjects was standardized during the work-day. The effects of two regimens of orange juice were studied: 1500 ml divided into five 300-ml portions during the day, and 300 ml once in the morning. Urine was collected, its pH recorded, and titrated with HCl to determine the mEq of base excreted per unit time. The consumption of 300 ml of orange juice did not significantly alter urinary pH. The consumption of 1500 of orange juice changed the urinary pH by an average of one pH unit. A change of this magnitude could cause clinically significant variation in the overall excretion pattern of acidic or basic drugs."}
{"id": "PMID:11689", "title": "Prevention of prematurity.", "content": "Although only about 8 per cent of pregnancies end prematurely, as much as 75 per cent of perinatal deaths are due to prematurity. Since it is difficult to identify the predisposing factors in individual cases and to prevent the premature onset of labor, it is necessary to try to arrest such labor when it occurs. A theoretical scheme for the mechanism of labor in the human subject is presented. This permits the identification of four possible points of attack: (1) replacement of progesterone to reduce the myometrial sensitivity to oxytocin, (2) administration of beta-mimetic agents to relax the uterus and make it unresponsive to stimuli, (3) administration of ethanol to block oxytocin secretion, and (4) administration of anti-inflammatory drugs to inhibit prostaglandin synthesis. Results obtained with ritodrine, a beta-mimetic agent, and with ethanol are presented as illustration. Ritodrine gave somewhat better results than ethanol, possibly because the treatment was continued after discharge of the patients.", "contents": "Prevention of prematurity. Although only about 8 per cent of pregnancies end prematurely, as much as 75 per cent of perinatal deaths are due to prematurity. Since it is difficult to identify the predisposing factors in individual cases and to prevent the premature onset of labor, it is necessary to try to arrest such labor when it occurs. A theoretical scheme for the mechanism of labor in the human subject is presented. This permits the identification of four possible points of attack: (1) replacement of progesterone to reduce the myometrial sensitivity to oxytocin, (2) administration of beta-mimetic agents to relax the uterus and make it unresponsive to stimuli, (3) administration of ethanol to block oxytocin secretion, and (4) administration of anti-inflammatory drugs to inhibit prostaglandin synthesis. Results obtained with ritodrine, a beta-mimetic agent, and with ethanol are presented as illustration. Ritodrine gave somewhat better results than ethanol, possibly because the treatment was continued after discharge of the patients."}
{"id": "PMID:11690", "title": "Effect of ritodrine on uterine activity, heart rate, and blood pressure in the pregnant sheep: combined use of alpha or beta blockade.", "content": "Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine.", "contents": "Effect of ritodrine on uterine activity, heart rate, and blood pressure in the pregnant sheep: combined use of alpha or beta blockade. Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine."}
{"id": "PMID:11691", "title": "Effect of propranolol infusion on the umbilical and uterine circulations of pregnant sheep.", "content": "Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits.", "contents": "Effect of propranolol infusion on the umbilical and uterine circulations of pregnant sheep. Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits."}
{"id": "PMID:11692", "title": "Exudative retinal detachment and scleritis in polyarteritis.", "content": "A 64-year-old white man, treated with systemic corticosteroids for five years, developed polyarteritis. He then developed a severe scleritis with an exudative retinal detachment in the right eye, which became blind and painful and was enucleated 23 months after onset of the scleritis. Histopathologic examination of the enucleated eye revealed granulomatous scleritis, chronic nongranulomatous uveitis, exudative retinal detachment, and perivasculitis of intrascleral, iris, ciliary body, and retinal blood vessels. Systemic findings were minimal and limited to elevated sedimentation rate, weight loss, mild anemia, and microscopic hematuria. Respiratory disease, severe kidney disease, hypertension, and arthritis were notably absent. A muscle biopsy established the diagnosis.", "contents": "Exudative retinal detachment and scleritis in polyarteritis. A 64-year-old white man, treated with systemic corticosteroids for five years, developed polyarteritis. He then developed a severe scleritis with an exudative retinal detachment in the right eye, which became blind and painful and was enucleated 23 months after onset of the scleritis. Histopathologic examination of the enucleated eye revealed granulomatous scleritis, chronic nongranulomatous uveitis, exudative retinal detachment, and perivasculitis of intrascleral, iris, ciliary body, and retinal blood vessels. Systemic findings were minimal and limited to elevated sedimentation rate, weight loss, mild anemia, and microscopic hematuria. Respiratory disease, severe kidney disease, hypertension, and arthritis were notably absent. A muscle biopsy established the diagnosis."}
{"id": "PMID:11693", "title": "The stability of ten antibiotics in artificial tear solutions.", "content": "We determined the relative potencies of penicillin G, carbenicillin, oxacillin, cephalothin, cephaloridine, gentamicin, kanamycin, neomycin, vancomycin, and bacitracin after their addition to three commercially available 0.5% hydroxypropyl methylcellulose artificial tear solutions in plastic squeeze bottles. We found no significant loss of antibiotic activity at room temperature over a period of seven days for all antibiotics except penicillin G, cephalothin, and cephaloridine. Three of the antibiotics were insoluble in one or more of the artificial tear solutions.", "contents": "The stability of ten antibiotics in artificial tear solutions. We determined the relative potencies of penicillin G, carbenicillin, oxacillin, cephalothin, cephaloridine, gentamicin, kanamycin, neomycin, vancomycin, and bacitracin after their addition to three commercially available 0.5% hydroxypropyl methylcellulose artificial tear solutions in plastic squeeze bottles. We found no significant loss of antibiotic activity at room temperature over a period of seven days for all antibiotics except penicillin G, cephalothin, and cephaloridine. Three of the antibiotics were insoluble in one or more of the artificial tear solutions."}
{"id": "PMID:11694", "title": "The closed eye environement: pH.", "content": "Earlier observations showed that unbuffered bathing media held by a closed chamber against the eye would become progressively more acid over a few minutes. Such shifts, however, when examined for the naturally closed eye, even for prolonged periods, were found to be within 1 pH unit of the open-eye measured average.", "contents": "The closed eye environement: pH. Earlier observations showed that unbuffered bathing media held by a closed chamber against the eye would become progressively more acid over a few minutes. Such shifts, however, when examined for the naturally closed eye, even for prolonged periods, were found to be within 1 pH unit of the open-eye measured average."}
{"id": "PMID:11695", "title": "Effect of virus infection on the inflammatory response. Depression of macrophage accumulation in influenza-infected mice.", "content": "To better define the mechanisms by which viruses depress immune function, the effect of influenza infection on the ability of macrophages to accumulate at sites of inflammation was determined. Mice were inoculated with virus, and their inflammatory response measured in vivo by counting the number of leukocytes which accumulated in the peritoneal cavity 2 days after an intraperitoneal injection of phytohemagglutinin. Mice infected with influenza had a 57% and 65% depression of total leukocyte and macrophage accumulation, respectively, as compared to the response of uninfected mice. In contrast, bacterial pneumonia did not produce a decrease in the macrophage response. This indicated that the depression was produced by the virus infection rather than being a nonspecific phenomenon accompanying any inflammatory focus in the lung. The in vitro chemotactic responsiveness of normal peritoneal macrophages incubated with infectious influenza virus was 53% of normal. These experiments suggest that influenza infection may depress a host's ability to mobilize macrophages to inflammatory sites in vivo by inhibiting their chemotactic responsiveness.", "contents": "Effect of virus infection on the inflammatory response. Depression of macrophage accumulation in influenza-infected mice. To better define the mechanisms by which viruses depress immune function, the effect of influenza infection on the ability of macrophages to accumulate at sites of inflammation was determined. Mice were inoculated with virus, and their inflammatory response measured in vivo by counting the number of leukocytes which accumulated in the peritoneal cavity 2 days after an intraperitoneal injection of phytohemagglutinin. Mice infected with influenza had a 57% and 65% depression of total leukocyte and macrophage accumulation, respectively, as compared to the response of uninfected mice. In contrast, bacterial pneumonia did not produce a decrease in the macrophage response. This indicated that the depression was produced by the virus infection rather than being a nonspecific phenomenon accompanying any inflammatory focus in the lung. The in vitro chemotactic responsiveness of normal peritoneal macrophages incubated with infectious influenza virus was 53% of normal. These experiments suggest that influenza infection may depress a host's ability to mobilize macrophages to inflammatory sites in vivo by inhibiting their chemotactic responsiveness."}
{"id": "PMID:11696", "title": "Formation of slow-reacting substance by guinea pig immunoglobulins.", "content": "The capacity of guinea pig antibodies to mediate the antigen-induced release of slow-reacting substance (SRS) in the rat peritoneal cavity is restricted to IgG2 and, to a lesser extent, to IgG1 populations of immunoglobulin. IgM and homocytotropic antibody of the reaginic type lacked this activity. The process was partially blocked by previous decomplementation of the rats, was not affected by previous reduction of the circulating leukocytes, and was partially suppressed by previous depletion of circulating platelets with an antiserum to rat platelets.", "contents": "Formation of slow-reacting substance by guinea pig immunoglobulins. The capacity of guinea pig antibodies to mediate the antigen-induced release of slow-reacting substance (SRS) in the rat peritoneal cavity is restricted to IgG2 and, to a lesser extent, to IgG1 populations of immunoglobulin. IgM and homocytotropic antibody of the reaginic type lacked this activity. The process was partially blocked by previous decomplementation of the rats, was not affected by previous reduction of the circulating leukocytes, and was partially suppressed by previous depletion of circulating platelets with an antiserum to rat platelets."}
{"id": "PMID:11697", "title": "Interaction of chemical carcinogens and drug-metabolizing enzymes in primary cultures of hepatic cells from the rat.", "content": "The experiments described in this paper have demonstrated that hepatocytes cultured on floating collagen membranes for periods of 10 days retain their ability to respond to the inducers of drug-metabolizing enzymes, phenobarbital and methylcholanthrene, by increases in cytochromes of the cytochrome P-450 complex. Since the regulation of these cytochromes is the rate-controlling factor in the metabolism of drugs and carcinogens in hepatocytes, such experiments indicate that hepatocytes cultured on floating collagen membranes retain those functions of the liver cell responsible for the metabolism and \"activation\" of carcinogenic substances. The data support this hypothesis and further indicate that this system may have potential application both in the investigation of hepatocarcinogenesis by chemicals in vitro and as a screening system for the detection of substances truly carcinogenic for the mammalian organism.", "contents": "Interaction of chemical carcinogens and drug-metabolizing enzymes in primary cultures of hepatic cells from the rat. The experiments described in this paper have demonstrated that hepatocytes cultured on floating collagen membranes for periods of 10 days retain their ability to respond to the inducers of drug-metabolizing enzymes, phenobarbital and methylcholanthrene, by increases in cytochromes of the cytochrome P-450 complex. Since the regulation of these cytochromes is the rate-controlling factor in the metabolism of drugs and carcinogens in hepatocytes, such experiments indicate that hepatocytes cultured on floating collagen membranes retain those functions of the liver cell responsible for the metabolism and \"activation\" of carcinogenic substances. The data support this hypothesis and further indicate that this system may have potential application both in the investigation of hepatocarcinogenesis by chemicals in vitro and as a screening system for the detection of substances truly carcinogenic for the mammalian organism."}
{"id": "PMID:11698", "title": "Properties of toad skin Na-K-ATPase with special reference to effect of temperature.", "content": "The NA-K-ATPase of toad skin was characteristically sensitive to Na, K, and ATP. It was not affected by amiloride, vasopressin, cAMP, and thyroxine, but stimulated by insulin. Ouabain, a potent inhibitor at 37 degrees C, did not inhibit the enzyme activity significantly at 23 degrees C. The optimal pH for the enzyme activity increased as temperature decreased. However, the optimal OH-/H+ ratio of the medium remained constant at 16 regardless of temperature. The Km for ATP remained unchanged between 37 and 8 degrees C if the OH-/H+ ratio was held constant at 16, but increased as temperature decreased if the pH of the medium was held constant at 7.4. The enzyme activity showed no appreciable variation between 37 and 20 degrees C with a constant OH-/H+ ratio of 16, whereas it decreased logarithmically at a constant pH of 7.4 over the same temperature range. These results indicate the presence of a typical Na-K-ATPase system in toad skin and that the enzyme is in the most active catalytic state at a fixed level of OH-/H+ ratio in the medium regardless of incubation temperature.", "contents": "Properties of toad skin Na-K-ATPase with special reference to effect of temperature. The NA-K-ATPase of toad skin was characteristically sensitive to Na, K, and ATP. It was not affected by amiloride, vasopressin, cAMP, and thyroxine, but stimulated by insulin. Ouabain, a potent inhibitor at 37 degrees C, did not inhibit the enzyme activity significantly at 23 degrees C. The optimal pH for the enzyme activity increased as temperature decreased. However, the optimal OH-/H+ ratio of the medium remained constant at 16 regardless of temperature. The Km for ATP remained unchanged between 37 and 8 degrees C if the OH-/H+ ratio was held constant at 16, but increased as temperature decreased if the pH of the medium was held constant at 7.4. The enzyme activity showed no appreciable variation between 37 and 20 degrees C with a constant OH-/H+ ratio of 16, whereas it decreased logarithmically at a constant pH of 7.4 over the same temperature range. These results indicate the presence of a typical Na-K-ATPase system in toad skin and that the enzyme is in the most active catalytic state at a fixed level of OH-/H+ ratio in the medium regardless of incubation temperature."}
{"id": "PMID:11699", "title": "Extracranial angiographic findings in giant cell (temporal) arteritis.", "content": "Angiograms of 10 patients with giant cell arteritis who had large-artery and aortic abnormalities were reviewed. The affected arteries had multiple stenotic areas, and occlusions were relatively common, usually located at the end of tapered stenotic segments. Bridging collateral arteries usually refilled the distal portion of the occluded artery. The laterations were seen most frequently in the subclavian, axillary, and brachial arters, and the arteriographic lesions reflected the clinical findings. Such arteriographic abnormalities are suggestive of giant cell arteritis in a patient over the age of 50. The differential diagnosis includes Takayasu's disease, arteriosclerosis, thoracic outlet syndrome, and ergotism.", "contents": "Extracranial angiographic findings in giant cell (temporal) arteritis. Angiograms of 10 patients with giant cell arteritis who had large-artery and aortic abnormalities were reviewed. The affected arteries had multiple stenotic areas, and occlusions were relatively common, usually located at the end of tapered stenotic segments. Bridging collateral arteries usually refilled the distal portion of the occluded artery. The laterations were seen most frequently in the subclavian, axillary, and brachial arters, and the arteriographic lesions reflected the clinical findings. Such arteriographic abnormalities are suggestive of giant cell arteritis in a patient over the age of 50. The differential diagnosis includes Takayasu's disease, arteriosclerosis, thoracic outlet syndrome, and ergotism."}
{"id": "PMID:11714", "title": "Analysis of body height in 829 patients with different forms of testicular pathology.", "content": "Analysis of body height was performed in the control group of 500 well-fertile men and in 829 patients with various forms of testicular pathology such as hypoplasia of testicles, unilateral and bilateral cryptorchism, hypogonadotrophic eunuchodism, and Klinefelter's syndrome. A statistically greater average height was found in bilateral cryptorchids, unilateral cryptorchids with an adequate spermiogenesis, hypogonadotrophic eunuchoids and chromatin-positive men. The greatest difference, when compared with the control group, was found in patients with a Klinefelter's syndrome. The authors hold the view that the plasmatic testosterone values are not the only factor conditioning the termination of the process of growth into height in males. Importance must also be given to the lowered sensibility of epiphysial growth zones to male sex hormone; this reduced sensibility is especially to be seen in chromatin-positive men.", "contents": "Analysis of body height in 829 patients with different forms of testicular pathology. Analysis of body height was performed in the control group of 500 well-fertile men and in 829 patients with various forms of testicular pathology such as hypoplasia of testicles, unilateral and bilateral cryptorchism, hypogonadotrophic eunuchodism, and Klinefelter's syndrome. A statistically greater average height was found in bilateral cryptorchids, unilateral cryptorchids with an adequate spermiogenesis, hypogonadotrophic eunuchoids and chromatin-positive men. The greatest difference, when compared with the control group, was found in patients with a Klinefelter's syndrome. The authors hold the view that the plasmatic testosterone values are not the only factor conditioning the termination of the process of growth into height in males. Importance must also be given to the lowered sensibility of epiphysial growth zones to male sex hormone; this reduced sensibility is especially to be seen in chromatin-positive men."}
{"id": "PMID:11718", "title": "Cutaneous necrotizing vasculitis and related disorders.", "content": "Leukocytoclastic vasculitis of the skin comprises several distinct clinical syndromes, each with immune complex deposition and some form of complement activation. Necrotizing vasculitides of larger blood vessels also produce skin lesions. These can be distinguished morphologically from those of small vessel vasculitis. Analysis of the features of these lesions is discussed.", "contents": "Cutaneous necrotizing vasculitis and related disorders. Leukocytoclastic vasculitis of the skin comprises several distinct clinical syndromes, each with immune complex deposition and some form of complement activation. Necrotizing vasculitides of larger blood vessels also produce skin lesions. These can be distinguished morphologically from those of small vessel vasculitis. Analysis of the features of these lesions is discussed."}
{"id": "PMID:11719", "title": "[Anesthesia for resections-anastomoses of the trachea and the tracheal bifurcation].", "content": "Resection and anastomosis of the trachea or the tracheal bifurcation, raises numerous problems, which will be discussed in a series of 81 patients: -there is more or less marked ventilatory insufficiency related to the degree of the stenosis, and difficulties of expectoration responsible for retention of sputum; -per-operative ventilation. One must choose between an intubation catheter of small caliber in order to overcome the stenosis, or a large catheter to remain above it. The problem is all the more delicate to solve when the stenosis is tighter and higher; -during the period when the trachea is open, the surgeon must intubate the central part of the trachea with a sterile catheter. If the division is low, it is necessary to intubate the main bronchi or one only, and then create a marked shunt effect which would be ill-supported by the patient; -It is advisable to remove the catheter at the end of the operation. Awakening should be perfect in order to cough to be immediately efficacious in a patient who often has to remain with his head flexed forwards.", "contents": "[Anesthesia for resections-anastomoses of the trachea and the tracheal bifurcation]. Resection and anastomosis of the trachea or the tracheal bifurcation, raises numerous problems, which will be discussed in a series of 81 patients: -there is more or less marked ventilatory insufficiency related to the degree of the stenosis, and difficulties of expectoration responsible for retention of sputum; -per-operative ventilation. One must choose between an intubation catheter of small caliber in order to overcome the stenosis, or a large catheter to remain above it. The problem is all the more delicate to solve when the stenosis is tighter and higher; -during the period when the trachea is open, the surgeon must intubate the central part of the trachea with a sterile catheter. If the division is low, it is necessary to intubate the main bronchi or one only, and then create a marked shunt effect which would be ill-supported by the patient; -It is advisable to remove the catheter at the end of the operation. Awakening should be perfect in order to cough to be immediately efficacious in a patient who often has to remain with his head flexed forwards."}
{"id": "PMID:11720", "title": "[Note on the care of tracheotomized patients].", "content": "After considering the indications for tracheotomy on his intensive care unit, the author describes the risks of this operation and the means of avoiding them. Out of 1940 patients admitted over a period of 5 years on the intensive care unit of the Royal Victoria Infirmary, Newcastle-on-Tyne, 175 were tracheotomised, inclusing 133 who were submitted to intermittent positive pressure ventilation. Only three patients had complications linked to the tracheotomy, complications which were the cause of the death of two of them.", "contents": "[Note on the care of tracheotomized patients]. After considering the indications for tracheotomy on his intensive care unit, the author describes the risks of this operation and the means of avoiding them. Out of 1940 patients admitted over a period of 5 years on the intensive care unit of the Royal Victoria Infirmary, Newcastle-on-Tyne, 175 were tracheotomised, inclusing 133 who were submitted to intermittent positive pressure ventilation. Only three patients had complications linked to the tracheotomy, complications which were the cause of the death of two of them."}
{"id": "PMID:11721", "title": "[Present role of selective intubation sounds in thoracic surgery].", "content": "After the indications for selective bronchial intubation, the methods of bronchial control by various techniques, together with their advantages and disadvantages, are discussed. A Advantages: -the right and left lungs are completely separated and if the tube is correctly placed in position, it will avoid any loss of secretions towards the healthy lung; -the lungs may be ventilated together or separately; -there is perfect water tightness within the traches and bronchi; -rapid deflation or inflation of each may be obtained without modifying the position of the tube. B Disadvantages: -there is an increased resistance to the air flow if only one lung is ventilated; -alone, a small diameter aspiration catheter may be used; -the catheters are costly, they may be difficult to introduce in small size subjects.", "contents": "[Present role of selective intubation sounds in thoracic surgery]. After the indications for selective bronchial intubation, the methods of bronchial control by various techniques, together with their advantages and disadvantages, are discussed. A Advantages: -the right and left lungs are completely separated and if the tube is correctly placed in position, it will avoid any loss of secretions towards the healthy lung; -the lungs may be ventilated together or separately; -there is perfect water tightness within the traches and bronchi; -rapid deflation or inflation of each may be obtained without modifying the position of the tube. B Disadvantages: -there is an increased resistance to the air flow if only one lung is ventilated; -alone, a small diameter aspiration catheter may be used; -the catheters are costly, they may be difficult to introduce in small size subjects."}
{"id": "PMID:11722", "title": "[Benign esophagotracheobronchial fistulas in adults].", "content": "Oeso-tracheal-bronchial fistulas are rare in adults and their precise etiology is often difficult to determine, apart from the traumatic causes. Their diagnosis, based on symptoms, is confirmed by tracheal, bronchial and esophageal endoscopy, esophageal opacification and esophageal cineradiography. Treatment should permit one to avoid progressive pulmonary deterioration. Fatal accidents of bronchial inudation are rare but have been observed, especially in tracheotomised subjects. Surgical cure is possible and should be carried out under conditions of security which are defined here. In cases of irreversible pulmonary damage, one should carry out during the same stage, resection of part of the lung. Whereas the prognosis of fistulas after tracheotomy or intubation is always reserved, that of primary fistulas is good, providing the surgical cure is carried out early.", "contents": "[Benign esophagotracheobronchial fistulas in adults]. Oeso-tracheal-bronchial fistulas are rare in adults and their precise etiology is often difficult to determine, apart from the traumatic causes. Their diagnosis, based on symptoms, is confirmed by tracheal, bronchial and esophageal endoscopy, esophageal opacification and esophageal cineradiography. Treatment should permit one to avoid progressive pulmonary deterioration. Fatal accidents of bronchial inudation are rare but have been observed, especially in tracheotomised subjects. Surgical cure is possible and should be carried out under conditions of security which are defined here. In cases of irreversible pulmonary damage, one should carry out during the same stage, resection of part of the lung. Whereas the prognosis of fistulas after tracheotomy or intubation is always reserved, that of primary fistulas is good, providing the surgical cure is carried out early."}
{"id": "PMID:11723", "title": "[Role of peridural anesthesia in thoracic surgery].", "content": "Periduralaneaesthesia by the cervical route (C6-C7 or C7-D1) or by the upper lumbar route with an ascending catheter, permit thoracic surgery in all its applications. The reduction in operative bleeding is an appreciable advantage of the method, and automatic nervous stability is remarkable. On the other hand, keeping the patient in the waking state is a definite disadvantage, especially in removal of one lung. As far as the anaesthetist is concerned he will be faced with difficulties of ventilation and bronchial aspiration. On the other hand, combined with slight general anaesthesia and tracheal intubation, peridural anaesthesia is definitely of interest. Furthermore, during the post-operative period, it is precious permitting a cough without pain and, in this respect, the comparison with anaesthesia of the inter-costal nerves, is worth discussins, each technique having special advantages.", "contents": "[Role of peridural anesthesia in thoracic surgery]. Periduralaneaesthesia by the cervical route (C6-C7 or C7-D1) or by the upper lumbar route with an ascending catheter, permit thoracic surgery in all its applications. The reduction in operative bleeding is an appreciable advantage of the method, and automatic nervous stability is remarkable. On the other hand, keeping the patient in the waking state is a definite disadvantage, especially in removal of one lung. As far as the anaesthetist is concerned he will be faced with difficulties of ventilation and bronchial aspiration. On the other hand, combined with slight general anaesthesia and tracheal intubation, peridural anaesthesia is definitely of interest. Furthermore, during the post-operative period, it is precious permitting a cough without pain and, in this respect, the comparison with anaesthesia of the inter-costal nerves, is worth discussins, each technique having special advantages."}
{"id": "PMID:11724", "title": "[Anesthesia for lung grafts].", "content": "The problems of anaesthesia for pulmonary transplantation are discussed from the theoretical and practical points of view. The problems of elimination of carbon dioxide and adequate oxygenation of the arterial blood, and protection of the transplanted lung, are considered. In the phase immediately after transplantation, the efficacy of gas exchanges are determined by reciprocal values of the resistance of the pulmonary artery, the resistance of the airways and the compliance of the transplanted and non-transplanted lung.", "contents": "[Anesthesia for lung grafts]. The problems of anaesthesia for pulmonary transplantation are discussed from the theoretical and practical points of view. The problems of elimination of carbon dioxide and adequate oxygenation of the arterial blood, and protection of the transplanted lung, are considered. In the phase immediately after transplantation, the efficacy of gas exchanges are determined by reciprocal values of the resistance of the pulmonary artery, the resistance of the airways and the compliance of the transplanted and non-transplanted lung."}
{"id": "PMID:11725", "title": "[Anesthesia and the postoperative period in non-urgent tracheal surgery. Apropos of 36 patients].", "content": "The authors report 36 cases of resection and suture for stenosis or tumour of the trachea and give details of their technique of anaesthesia, the post-operative follow-up and their results. The development of fiber endoscopy and simplification of intubation, increases the security of the patient, facilitates the task of the anaesthetist and thus improves greatly the operative conditions and post-operative period.", "contents": "[Anesthesia and the postoperative period in non-urgent tracheal surgery. Apropos of 36 patients]. The authors report 36 cases of resection and suture for stenosis or tumour of the trachea and give details of their technique of anaesthesia, the post-operative follow-up and their results. The development of fiber endoscopy and simplification of intubation, increases the security of the patient, facilitates the task of the anaesthetist and thus improves greatly the operative conditions and post-operative period."}
{"id": "PMID:11717", "title": "Lorazepam premedication: lack of recall and relief of anxiety.", "content": "Premedication with lorazepam (4 mg), diazepam (10 mg), and a placebo was compared in a randomized, double-blind study of 95 adult surgical patients. Comparisons were made of recall of a memory card and events of the operative day, relief of anxiety, degree of somnolence, effects on blood pressure and heart rate, and incidence of side effects. Lorazepam produced a significant lack of recall (antegrade amnesia) compared to the other agents. Lorazepam produced a greater antianxiety effect than placebo and a greater degree of somnolence than diazepam or placebo. Since no adverse effects on blood pressure or heart rate occurred, lorazepam appears to show promise as a premedicant.", "contents": "Lorazepam premedication: lack of recall and relief of anxiety. Premedication with lorazepam (4 mg), diazepam (10 mg), and a placebo was compared in a randomized, double-blind study of 95 adult surgical patients. Comparisons were made of recall of a memory card and events of the operative day, relief of anxiety, degree of somnolence, effects on blood pressure and heart rate, and incidence of side effects. Lorazepam produced a significant lack of recall (antegrade amnesia) compared to the other agents. Lorazepam produced a greater antianxiety effect than placebo and a greater degree of somnolence than diazepam or placebo. Since no adverse effects on blood pressure or heart rate occurred, lorazepam appears to show promise as a premedicant."}
{"id": "PMID:11726", "title": "[Technic of pleural drainage (emergency pleural drainage)].", "content": "Pleural effusion is still often poorly drained: - incorrect introduction of the drain into the thorax, - ill-chosen position of the drain. Simple drainage, a minima, is considered here, that which requires no broad surgical incision and which, in cases of effusion with compression of the lung, is often a life saving procedure which any doctor should be able to carry out, especially if he deals with emergencies. The surest technique consists of placing a No. 30 drain, using a pleurotomy trocart, type Monod or Coquelet, under local anaesthesia. Introduction of the drain using a forceps after an incision with the scalpel blade is only justified if one has no trocart available. So-called disposable drains, mounted on a pointed bevelled needle prepared in advance, are practical but dangerous. Capillary drainages are methods of second choice. They are often excluded within short delays. The efficacy of the drainage depends on its position.", "contents": "[Technic of pleural drainage (emergency pleural drainage)]. Pleural effusion is still often poorly drained: - incorrect introduction of the drain into the thorax, - ill-chosen position of the drain. Simple drainage, a minima, is considered here, that which requires no broad surgical incision and which, in cases of effusion with compression of the lung, is often a life saving procedure which any doctor should be able to carry out, especially if he deals with emergencies. The surest technique consists of placing a No. 30 drain, using a pleurotomy trocart, type Monod or Coquelet, under local anaesthesia. Introduction of the drain using a forceps after an incision with the scalpel blade is only justified if one has no trocart available. So-called disposable drains, mounted on a pointed bevelled needle prepared in advance, are practical but dangerous. Capillary drainages are methods of second choice. They are often excluded within short delays. The efficacy of the drainage depends on its position."}
{"id": "PMID:11727", "title": "[Tracheobronchial ruptures seen in emergencies. Viewpoint of the anesthesiologist].", "content": "At the Marie Lannelongue surgical centre between 1964 and 1975, out of 278 patients with trauma of the thorax, we noted only 10 cases of tracheal-bronchial rupture admitted as an emergency = 9 ruptures due to closed trauma of the thorax, one with division of the lower part of the trachea. Analysis of these cases showed in particular:-the notion of violent trauma in -young subjects (average age: 20 years). In these thoracic injuries suspected of tracheal-bronchial rupture, the anaesthetist intervenes in four early stages: 1) arrival of the injured patient 2) bronchoscopy-diagnosis 3) surgical operation, the anaesthetic problems are linked to various factors, the most important of which are the very precarious cardio-respiratory condition, the lack of information and, sometimes, the lack of time. 4) Post-operative respiratory resuscitation.", "contents": "[Tracheobronchial ruptures seen in emergencies. Viewpoint of the anesthesiologist]. At the Marie Lannelongue surgical centre between 1964 and 1975, out of 278 patients with trauma of the thorax, we noted only 10 cases of tracheal-bronchial rupture admitted as an emergency = 9 ruptures due to closed trauma of the thorax, one with division of the lower part of the trachea. Analysis of these cases showed in particular:-the notion of violent trauma in -young subjects (average age: 20 years). In these thoracic injuries suspected of tracheal-bronchial rupture, the anaesthetist intervenes in four early stages: 1) arrival of the injured patient 2) bronchoscopy-diagnosis 3) surgical operation, the anaesthetic problems are linked to various factors, the most important of which are the very precarious cardio-respiratory condition, the lack of information and, sometimes, the lack of time. 4) Post-operative respiratory resuscitation."}
{"id": "PMID:11728", "title": "[Emergency treatment of tracheal and bronchial foreign bodies].", "content": "Basing their report on personal experience of more than 300 tracheal or bronchial foreign bodies, the authors emphasize: -the difficulty of extraction, even in very expert hands. -the absolute necessity of a fully trained operator, and experienced anaesthetist and appropriate material. Apart from acute respiratory distress, they consider preferable to defer operation for a few hours, under strict supervision, in order to make available all these optimal conditions.", "contents": "[Emergency treatment of tracheal and bronchial foreign bodies]. Basing their report on personal experience of more than 300 tracheal or bronchial foreign bodies, the authors emphasize: -the difficulty of extraction, even in very expert hands. -the absolute necessity of a fully trained operator, and experienced anaesthetist and appropriate material. Apart from acute respiratory distress, they consider preferable to defer operation for a few hours, under strict supervision, in order to make available all these optimal conditions."}
{"id": "PMID:11729", "title": "[Extraction of intrabronchial foreign bodies in young patients in a surgical unit].", "content": "The authors report a study of 35 cases of intra-bronchial foreign bodies in young subjects (average age 6 years). This shows that, more than the age of the child, or the duration of the presence of the object, its nature, has an influence on the possibilities of extraction by bronchoscopy or by thoracotomy. Whatever the nature of the foreign body, the authors emphasize the importance of the quality of the team formed by the endoscopist and the anaesthetist, repeated attempts at bronchoscopy compromise success and may lead to tracheotomy.", "contents": "[Extraction of intrabronchial foreign bodies in young patients in a surgical unit]. The authors report a study of 35 cases of intra-bronchial foreign bodies in young subjects (average age 6 years). This shows that, more than the age of the child, or the duration of the presence of the object, its nature, has an influence on the possibilities of extraction by bronchoscopy or by thoracotomy. Whatever the nature of the foreign body, the authors emphasize the importance of the quality of the team formed by the endoscopist and the anaesthetist, repeated attempts at bronchoscopy compromise success and may lead to tracheotomy."}
{"id": "PMID:11730", "title": "Glucose and insulin responses in sheep subjected to a second episode of hemorrhagic shock.", "content": "These studies indicated that the responses of the sheep beta cell parallel mnay of those seen in man. Regulation by pH, potassium, and epinephrine and suggested, as is the existence of a two-pool system for insulin synthesis and release which is responsive to glucose. Differences in glucose and insulin responses following a second episode of shock are noted. It is shown that the addition of hypertonic glucose to a resuscitation regimen is associated with a response to a second episode of shock that is more nearly like that to a first episode of shock.", "contents": "Glucose and insulin responses in sheep subjected to a second episode of hemorrhagic shock. These studies indicated that the responses of the sheep beta cell parallel mnay of those seen in man. Regulation by pH, potassium, and epinephrine and suggested, as is the existence of a two-pool system for insulin synthesis and release which is responsive to glucose. Differences in glucose and insulin responses following a second episode of shock are noted. It is shown that the addition of hypertonic glucose to a resuscitation regimen is associated with a response to a second episode of shock that is more nearly like that to a first episode of shock."}
{"id": "PMID:11731", "title": "Chemical mediation in Coelenterata.", "content": "This paper reports the results of a pharmacological survey of drug action on muscle preparations of the anthozoan Bunodosoma caissarum. A critical review of previous results of drug action on Coelenterate neuromuscular junction is also given. The preparations responded only to body wall homogenates and acetylcholine. Sympathomimeticamines (adrenaline and nor-adrenaline), indolalkylamines (tryptamine, serotonin) and other drugs (tyramine, histamine, 1-glutamate and GABA) showed no action. The view that the Coelenterates do not employ acetylcholine as a neurotransmitter is discussed.", "contents": "Chemical mediation in Coelenterata. This paper reports the results of a pharmacological survey of drug action on muscle preparations of the anthozoan Bunodosoma caissarum. A critical review of previous results of drug action on Coelenterate neuromuscular junction is also given. The preparations responded only to body wall homogenates and acetylcholine. Sympathomimeticamines (adrenaline and nor-adrenaline), indolalkylamines (tryptamine, serotonin) and other drugs (tyramine, histamine, 1-glutamate and GABA) showed no action. The view that the Coelenterates do not employ acetylcholine as a neurotransmitter is discussed."}
{"id": "PMID:11735", "title": "Studies on the carbohydrate metabolism in psoriatic epidermis.", "content": "Enzymic activities and cofactor levels in the epidermis are reviewed with special regard to psoriasis and the papulosquamous disorders lichen simplex and lichen planus. The metabolism of nicotinamide adenine dinucleotide phosphate and its dependent pathways seems to deviate in psoriasis from that in the contrasted dermatoses, in normal skin in health and in skin during the process of wound healing. The mitochondrial function also differs between psoriatic and normal skin. In some conditions in psoriasis this function cannot be seen to deviate from normality, however. The regulation and control of mitochondrial function in psoriasis might be another area in which future investigations may yield significant information on the pathophysiology in this skin disease.", "contents": "Studies on the carbohydrate metabolism in psoriatic epidermis. Enzymic activities and cofactor levels in the epidermis are reviewed with special regard to psoriasis and the papulosquamous disorders lichen simplex and lichen planus. The metabolism of nicotinamide adenine dinucleotide phosphate and its dependent pathways seems to deviate in psoriasis from that in the contrasted dermatoses, in normal skin in health and in skin during the process of wound healing. The mitochondrial function also differs between psoriatic and normal skin. In some conditions in psoriasis this function cannot be seen to deviate from normality, however. The regulation and control of mitochondrial function in psoriasis might be another area in which future investigations may yield significant information on the pathophysiology in this skin disease."}
{"id": "PMID:11736", "title": "[Carbohydrate and pyruvic acid degradation pathways in Fusidium coccineum strains with varying levels of antibiotic synthesis].", "content": "A number of enzymes and reactions of glycolysis, pentose-phosphate cycle and degradation of pyruvic acid in strains of F. coccineum with various levels of antibiotic production was studied comparatively. The experiments showed that highly productive strains were characterized by higher activity of the NADP-deficient enzymes of the pentoze-phosphate cycle as compared to the low active strains. The activity levels of glycolytic enzymes, such as fructose-diphosphate-aldolase and 3-phosphoglycerolaldehydehydrogenase did not practically differ. Significant differences were found in the reactions of puryvic acid degradation: the activity of cytoplasmic pyruvatedecarboxylase in the mutant with high antibiotic production level was lower than that in the low productive strain, while oxidation of the pyruvate of the mitochondrial fraction was on the contrary more intensive than in the highly productive strain. Therefore, metabilism in the strains studied was characterized by ever-increasing biochemical changes with an increase in their antibiotic productivity. Lowering of the growth rate of the mutants as their capacity for antibiotic supersynthesis increased and subsequently the anabolic processes became more intensive was accompanied by increasing derepression of the key enzymes of carbohydrate metabolism and in particular NADR-deficient dehydrogenase of the pentose cycle and pyruvatedehydrogenase, significant for fusidin biosynthesis and providing production of the antibiotic of steroid nature by cofactor NADP-H and acetyl-KoA, the primary precursor.", "contents": "[Carbohydrate and pyruvic acid degradation pathways in Fusidium coccineum strains with varying levels of antibiotic synthesis]. A number of enzymes and reactions of glycolysis, pentose-phosphate cycle and degradation of pyruvic acid in strains of F. coccineum with various levels of antibiotic production was studied comparatively. The experiments showed that highly productive strains were characterized by higher activity of the NADP-deficient enzymes of the pentoze-phosphate cycle as compared to the low active strains. The activity levels of glycolytic enzymes, such as fructose-diphosphate-aldolase and 3-phosphoglycerolaldehydehydrogenase did not practically differ. Significant differences were found in the reactions of puryvic acid degradation: the activity of cytoplasmic pyruvatedecarboxylase in the mutant with high antibiotic production level was lower than that in the low productive strain, while oxidation of the pyruvate of the mitochondrial fraction was on the contrary more intensive than in the highly productive strain. Therefore, metabilism in the strains studied was characterized by ever-increasing biochemical changes with an increase in their antibiotic productivity. Lowering of the growth rate of the mutants as their capacity for antibiotic supersynthesis increased and subsequently the anabolic processes became more intensive was accompanied by increasing derepression of the key enzymes of carbohydrate metabolism and in particular NADR-deficient dehydrogenase of the pentose cycle and pyruvatedehydrogenase, significant for fusidin biosynthesis and providing production of the antibiotic of steroid nature by cofactor NADP-H and acetyl-KoA, the primary precursor."}
{"id": "PMID:11737", "title": "[Dependence of erythromycin biosynthesis on the active acidity of the medium].", "content": "Dependence of erythromycin biosynthesis on the medium active acidity was studied by the following methods: by changing pH of the initial medium, by changing the concentration of the medium components determining the active acidity of the culture, by using buffer mixtures by automatic control of pH. It was found that pH of the initial medium within 5.7-8.1 had no effect on the culture growth. Biosynthesis of erythromycin markedly decreased at pH 6.3 or lower. The values of pH within 6.6-7.5 (optimal values 6.7-6.9) were favourable for the antibiotic biosynthesis. At pH 6.2-6.3 the antibiotic accumulation was equal to 5-10 per cent of the control.", "contents": "[Dependence of erythromycin biosynthesis on the active acidity of the medium]. Dependence of erythromycin biosynthesis on the medium active acidity was studied by the following methods: by changing pH of the initial medium, by changing the concentration of the medium components determining the active acidity of the culture, by using buffer mixtures by automatic control of pH. It was found that pH of the initial medium within 5.7-8.1 had no effect on the culture growth. Biosynthesis of erythromycin markedly decreased at pH 6.3 or lower. The values of pH within 6.6-7.5 (optimal values 6.7-6.9) were favourable for the antibiotic biosynthesis. At pH 6.2-6.3 the antibiotic accumulation was equal to 5-10 per cent of the control."}
{"id": "PMID:11738", "title": "[Determination of rifamycin B activity in culture liquids and in preparations with varying degrees of purity].", "content": "A possibility of using the biological method of rifamycin B activity determination in the fermentation broth and dry preparations of various purity levels was studied. It was found that the biological method was useful only for determination of rifamycin B activity in preparations containing not less than 850 gamma/mg of the main product. When the activity of rifamycin B was determined in the fermentation broth and crude preparations containing less than 800 gamma/mg of the main product, the results of the biological assay were always higher as compared to those of spectrophotometrical estimation. It was accounted for the effect of other rifamycin types possessing high biological activity.", "contents": "[Determination of rifamycin B activity in culture liquids and in preparations with varying degrees of purity]. A possibility of using the biological method of rifamycin B activity determination in the fermentation broth and dry preparations of various purity levels was studied. It was found that the biological method was useful only for determination of rifamycin B activity in preparations containing not less than 850 gamma/mg of the main product. When the activity of rifamycin B was determined in the fermentation broth and crude preparations containing less than 800 gamma/mg of the main product, the results of the biological assay were always higher as compared to those of spectrophotometrical estimation. It was accounted for the effect of other rifamycin types possessing high biological activity."}
{"id": "PMID:11739", "title": "[Stability of 6-beta-[(hexahydro-1H-azepin-l-yl)methyleneamino]-penicillanic acid in aqueous solutions].", "content": "Stability of acqueous solutions of 6-beta-[(hexahydro-IH-azepin-I-yl)methylenamino] penicillanic acid at various values of pH and temperature was studied. It was found that inactivation of the antibiotic in both the acid and the alkaline medium proceeded according to the equation of the 1st order. At pH 1.3 and a temperature of 35 degrees the half life of the antibiotic was 7 hours. The activation energy calculated according to the Arrenius equation was 13.5 kcal/mol at pH 1.3 and 22.2 kcal/mol at pH 10.5. The antibiotic was inactivated in glycol and phosphate buffers. Its qualitative analysis was performed according to an improved iodometric method.", "contents": "[Stability of 6-beta-[(hexahydro-1H-azepin-l-yl)methyleneamino]-penicillanic acid in aqueous solutions]. Stability of acqueous solutions of 6-beta-[(hexahydro-IH-azepin-I-yl)methylenamino] penicillanic acid at various values of pH and temperature was studied. It was found that inactivation of the antibiotic in both the acid and the alkaline medium proceeded according to the equation of the 1st order. At pH 1.3 and a temperature of 35 degrees the half life of the antibiotic was 7 hours. The activation energy calculated according to the Arrenius equation was 13.5 kcal/mol at pH 1.3 and 22.2 kcal/mol at pH 10.5. The antibiotic was inactivated in glycol and phosphate buffers. Its qualitative analysis was performed according to an improved iodometric method."}
{"id": "PMID:11740", "title": "[Interaction of morphocycline with beryllium ions].", "content": "Behaviour of morphocycline (H5R) and its complex with beryllium ions in acqueous solutions was studied fluorimetrically. The ionization constants of H5R were estimated at pH 1.5-15 according to the data of fluorimetric determination with respect to OH-group: pK1 6.40, pK2 8.25, pK3 10.65, pK4 11.30. Two constants characterizing the deprotonization process with respect to the carbonylic group and nitrogen were also estimated: pK01--1.0 (greater than C = 0) and pK02 4.75 (--N=). Formation of an intensively fluorescing compound less than [Be3(OH)3(H2O2)5]2HR greater than 2+ was observed at pH 6.0-7.0. The cause of such intensive fluorescence was deformation of ion [Be3(OH)3(H2O)6]3+ because of its exclusion from the coordinating sphere of one molecule of water during the complex formation and decreasing of level H comes from II as compared to the morphocycline level II comes from n. A procedure for detecting morphocycline in the blood of humans and animals was developed.", "contents": "[Interaction of morphocycline with beryllium ions]. Behaviour of morphocycline (H5R) and its complex with beryllium ions in acqueous solutions was studied fluorimetrically. The ionization constants of H5R were estimated at pH 1.5-15 according to the data of fluorimetric determination with respect to OH-group: pK1 6.40, pK2 8.25, pK3 10.65, pK4 11.30. Two constants characterizing the deprotonization process with respect to the carbonylic group and nitrogen were also estimated: pK01--1.0 (greater than C = 0) and pK02 4.75 (--N=). Formation of an intensively fluorescing compound less than [Be3(OH)3(H2O2)5]2HR greater than 2+ was observed at pH 6.0-7.0. The cause of such intensive fluorescence was deformation of ion [Be3(OH)3(H2O)6]3+ because of its exclusion from the coordinating sphere of one molecule of water during the complex formation and decreasing of level H comes from II as compared to the morphocycline level II comes from n. A procedure for detecting morphocycline in the blood of humans and animals was developed."}
{"id": "PMID:11741", "title": "[Dependence of the mutagenic effect of N-nitroso-N-methylbiuret on the pH index].", "content": "The mutagenic effect of nitrosocompounds is known to be dependent on pH. The effect of N-nitrozo-N-methylbiuret on the conidia of Penicillium chrysogenum was studied within the ranges of pH from 5.0 to 7.0, the role of the buffer and distilled water being also considered. It was found that survival, morphological variation and induction of biochemical mutants depended on the value of pH. The optimal conditions for the culture treatment at the exposures tested were provided at pH 6.0 with the use of a phosphate buffer mixture as a substrate.", "contents": "[Dependence of the mutagenic effect of N-nitroso-N-methylbiuret on the pH index]. The mutagenic effect of nitrosocompounds is known to be dependent on pH. The effect of N-nitrozo-N-methylbiuret on the conidia of Penicillium chrysogenum was studied within the ranges of pH from 5.0 to 7.0, the role of the buffer and distilled water being also considered. It was found that survival, morphological variation and induction of biochemical mutants depended on the value of pH. The optimal conditions for the culture treatment at the exposures tested were provided at pH 6.0 with the use of a phosphate buffer mixture as a substrate."}
{"id": "PMID:11743", "title": "Initial fast reaction of bromine on reovirus in turbulent flowing water.", "content": "An apparatus is described for precise observation of the kinetics of the initial fast reaction of bromine with reovirus in turbulent flowing water. When quantitative electron microscopy shows that virus suspensions are essentially all single particles, the loss of infectivity follows first-order kinetics, the plaque titer falling at the rate of 3 log10 units/s at pH 7, 2 C, and at a 3-muM bromine concentration. Virus suspensions containing small aggregates (2 to 10/clump) exhibit a constantly decreasing disinfection rate with bromine. At a survival level of 10(-3) for single virions, the aggregated preparations have lost only 99% of their plaque titer and 10(-4) is reached only after 4 s of exposure. The disinfection rate does not appear to be a simple function of the size and frequency of aggregates in the virus suspension even when the aggregates contain no foreign material. Unpurified virus preparations (crude freeze-thaw lysates of infected cells) are shown, by zonal centrifugation, to contain 50% to over 90% of the infectivity in large, fast sedimenting aggregates. Such aggregates would strongly influence the bromine resistance of virus in polluted water.", "contents": "Initial fast reaction of bromine on reovirus in turbulent flowing water. An apparatus is described for precise observation of the kinetics of the initial fast reaction of bromine with reovirus in turbulent flowing water. When quantitative electron microscopy shows that virus suspensions are essentially all single particles, the loss of infectivity follows first-order kinetics, the plaque titer falling at the rate of 3 log10 units/s at pH 7, 2 C, and at a 3-muM bromine concentration. Virus suspensions containing small aggregates (2 to 10/clump) exhibit a constantly decreasing disinfection rate with bromine. At a survival level of 10(-3) for single virions, the aggregated preparations have lost only 99% of their plaque titer and 10(-4) is reached only after 4 s of exposure. The disinfection rate does not appear to be a simple function of the size and frequency of aggregates in the virus suspension even when the aggregates contain no foreign material. Unpurified virus preparations (crude freeze-thaw lysates of infected cells) are shown, by zonal centrifugation, to contain 50% to over 90% of the infectivity in large, fast sedimenting aggregates. Such aggregates would strongly influence the bromine resistance of virus in polluted water."}
{"id": "PMID:11744", "title": "Synthesis of staphylococcal enterotoxin A and nuclease under controlled fermentor conditions.", "content": "The production of enterotoxin A and nuclease by Staphylococcus aureus strain 100 was studied in a 1.0-liter fermentor. The effects of the gas flow rate, pH, and dissolved oxygen were evaluated. Toxin and nuclease secretion occurred under all conditions which permitted growth of the organism. Final yields of toxin and nuclease in cultures grown at constant air flow rates, ranging from 50 to 500 cm3 per min, were higher at successively higher flow rates. An optimum flow rate for either toxin or nuclease production was not observed. When the aeration rate alone or aeration rate and pH were held constant, the dissolved oxygen levels in the culture decreased from the initial 100% level to 0 to 5% 3 to 4 h after inoculation. The O2 demand of the culture then maintained this level for an additional 4 to 5 h. This low dissolved oxygen interval was characterized by rapid growth and extracellular protein production. Controlling the dissolved oxygen at a constant level throughout growth did not increase the final levels of toxin and nuclease above those achieved at the respective constant pH values. Growth under the influence of a constant aeration rate of 500 cm3 per min and a constant pH of 6.5 and 7.0 yielded the highest titers of nuclease (1,550 units/ml) and toxin (10.5 mug/ml) obtained in any of the fermentations conducted in this study. Sparging fermentor cultures with pure oxygen at a rate of 100 cm3 per min yielded growth and extracellular protein levels similar to those achieved at the sparge rate of 500 cm3 of air per min. Controlling the dissolved oxygen at 100% of pure oxygen saturation appeared to inhibit the culture, as the final cultural turbidity as well as the levels of toxin and nuclease were reduced. These data indicate that enterotoxin and nuclease secretions are closely associated with the growth of strain 100. Analyses of the production rates of these components indicated that early log phase was the most efficient production interval in the growth cycle and that this efficiency was increased by pH control at 6.7 to 6.8 and dissolved oxygen control at 10% of air saturation.", "contents": "Synthesis of staphylococcal enterotoxin A and nuclease under controlled fermentor conditions. The production of enterotoxin A and nuclease by Staphylococcus aureus strain 100 was studied in a 1.0-liter fermentor. The effects of the gas flow rate, pH, and dissolved oxygen were evaluated. Toxin and nuclease secretion occurred under all conditions which permitted growth of the organism. Final yields of toxin and nuclease in cultures grown at constant air flow rates, ranging from 50 to 500 cm3 per min, were higher at successively higher flow rates. An optimum flow rate for either toxin or nuclease production was not observed. When the aeration rate alone or aeration rate and pH were held constant, the dissolved oxygen levels in the culture decreased from the initial 100% level to 0 to 5% 3 to 4 h after inoculation. The O2 demand of the culture then maintained this level for an additional 4 to 5 h. This low dissolved oxygen interval was characterized by rapid growth and extracellular protein production. Controlling the dissolved oxygen at a constant level throughout growth did not increase the final levels of toxin and nuclease above those achieved at the respective constant pH values. Growth under the influence of a constant aeration rate of 500 cm3 per min and a constant pH of 6.5 and 7.0 yielded the highest titers of nuclease (1,550 units/ml) and toxin (10.5 mug/ml) obtained in any of the fermentations conducted in this study. Sparging fermentor cultures with pure oxygen at a rate of 100 cm3 per min yielded growth and extracellular protein levels similar to those achieved at the sparge rate of 500 cm3 of air per min. Controlling the dissolved oxygen at 100% of pure oxygen saturation appeared to inhibit the culture, as the final cultural turbidity as well as the levels of toxin and nuclease were reduced. These data indicate that enterotoxin and nuclease secretions are closely associated with the growth of strain 100. Analyses of the production rates of these components indicated that early log phase was the most efficient production interval in the growth cycle and that this efficiency was increased by pH control at 6.7 to 6.8 and dissolved oxygen control at 10% of air saturation."}
{"id": "PMID:11745", "title": "Inactivation by bromine of single poliovirus particles in water.", "content": "Quantitative electron microscopy shows that Freon-extracted poliovirus, velocity banded in a sucrose gradient, contains over 95% single particles. This well-dispersed virus reacts quite rapidly with bromine in turbulent flowing water, losing plaque titer at the rate of one log10 unit in 10s at pH 7, 2 C, and at a bromine concentration of 2.2 muM. At 10 and 20 C the rate of disinfection (log10 plaque-forming units per second) is faster, and at both temperatures it increases in approximately linear fashion with increasing bromine concentration. At 2 C such a linear relationship is not observed.", "contents": "Inactivation by bromine of single poliovirus particles in water. Quantitative electron microscopy shows that Freon-extracted poliovirus, velocity banded in a sucrose gradient, contains over 95% single particles. This well-dispersed virus reacts quite rapidly with bromine in turbulent flowing water, losing plaque titer at the rate of one log10 unit in 10s at pH 7, 2 C, and at a bromine concentration of 2.2 muM. At 10 and 20 C the rate of disinfection (log10 plaque-forming units per second) is faster, and at both temperatures it increases in approximately linear fashion with increasing bromine concentration. At 2 C such a linear relationship is not observed."}
{"id": "PMID:11753", "title": "Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.", "content": "The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and  after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive.", "contents": "Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration. The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and  after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive."}
{"id": "PMID:11754", "title": "Changes in the interstitial fluid and the muscle water in rabbits in hemorrhagic shock.", "content": "Dynamics and changes in the biochemical composition in the interstitial fluid and the muscle water were studied in hemorrhagic shock. The interstitial fluid was collected from implanted perforated capsules. Muscle biopsies were examined with regard to their water content by the steady state magnetic nuclear resonance spectroscopy. The consistent and what appears to be the most significant changes were the fall in the interstitial fluid pressures, the quantitative reduction of muscle water, a sharp fall in the blood and interstitial blood pH, the moderate hyperkalemia and lack of change in blood an interstitial fluid sodium, and the rise in blood glucose levels not accompanied by a rise in the interstitial fluid glucose levels.", "contents": "Changes in the interstitial fluid and the muscle water in rabbits in hemorrhagic shock. Dynamics and changes in the biochemical composition in the interstitial fluid and the muscle water were studied in hemorrhagic shock. The interstitial fluid was collected from implanted perforated capsules. Muscle biopsies were examined with regard to their water content by the steady state magnetic nuclear resonance spectroscopy. The consistent and what appears to be the most significant changes were the fall in the interstitial fluid pressures, the quantitative reduction of muscle water, a sharp fall in the blood and interstitial blood pH, the moderate hyperkalemia and lack of change in blood an interstitial fluid sodium, and the rise in blood glucose levels not accompanied by a rise in the interstitial fluid glucose levels."}
{"id": "PMID:11755", "title": "Cardiac function and metabolism following hemorrhage in the newborn lamb.", "content": "Cardiac performance was assessed in 33 lambs less than 1 to 5 days of age by means of left ventricular function curves. Performance was quantified by determining stroke volume ejected at end diastolic pressure 10 cm H2O (SV10) with constant afterload. Coronary flow, myocardial O2 consumption (MVO2), blood gas tensions and pH were determined. Measurements were obtained before and at 30 min intervals following hemorrhage to 30 mm Hg arterial pressure, and in controls (arterial pressure 75 mm Hg). Effects of metabolic acidosis, hypercapnia and beta-blockade were determined. In control lambs acidosis and hypercapnia failed to reduce SV10 after two hours. In hemorrhaged animals both factors sharply reduced SV10 and lambs with prior beta-blockade showed no greater reduction. MVO2 fell following hemorrhage but did not differ with metabolic conditions and did not relate to SV10. It is concluded that beta-adrenergic function is critically important in preserving left ventricular performance in newborn exposed to acidosis or hypercapnia. With sustained hemorrhage this mechanism fails leading to a significant depression of ventricular function. MVO2 was not a determining factor in these studies.", "contents": "Cardiac function and metabolism following hemorrhage in the newborn lamb. Cardiac performance was assessed in 33 lambs less than 1 to 5 days of age by means of left ventricular function curves. Performance was quantified by determining stroke volume ejected at end diastolic pressure 10 cm H2O (SV10) with constant afterload. Coronary flow, myocardial O2 consumption (MVO2), blood gas tensions and pH were determined. Measurements were obtained before and at 30 min intervals following hemorrhage to 30 mm Hg arterial pressure, and in controls (arterial pressure 75 mm Hg). Effects of metabolic acidosis, hypercapnia and beta-blockade were determined. In control lambs acidosis and hypercapnia failed to reduce SV10 after two hours. In hemorrhaged animals both factors sharply reduced SV10 and lambs with prior beta-blockade showed no greater reduction. MVO2 fell following hemorrhage but did not differ with metabolic conditions and did not relate to SV10. It is concluded that beta-adrenergic function is critically important in preserving left ventricular performance in newborn exposed to acidosis or hypercapnia. With sustained hemorrhage this mechanism fails leading to a significant depression of ventricular function. MVO2 was not a determining factor in these studies."}
{"id": "PMID:11757", "title": "Structure-activity relationship studies of derivatives of aminotetralins and open chain analogs in relation to beta and alpha-adrenoceptor agonist activities.", "content": "Some derivatives of aminotetralins and their open chain analogs were tested for their ability to alter blood pressure and heart rate in anesthetized cats with both vagi nerves sectioned and their ability to relax tracheal smooth muscle of guinea-pigs. TL-257 and JOD-213, tertiary amines, produced weak alpha-adrenoceptor stimulating activity while JOD-176 and JOD-211, secondary amines, showed beta-adrenoceptor stimulating activity. Another compounds, M-8, an aminotetralin that is a secondary amine, produced alpha and beta adrenoceptor stimulating activity. The beta-adrenoceptor stimulating activities of M-8 and JOD-176 showed more specificity for beta2-adrenoceptors than for beta1-adrenoceptors.", "contents": "Structure-activity relationship studies of derivatives of aminotetralins and open chain analogs in relation to beta and alpha-adrenoceptor agonist activities. Some derivatives of aminotetralins and their open chain analogs were tested for their ability to alter blood pressure and heart rate in anesthetized cats with both vagi nerves sectioned and their ability to relax tracheal smooth muscle of guinea-pigs. TL-257 and JOD-213, tertiary amines, produced weak alpha-adrenoceptor stimulating activity while JOD-176 and JOD-211, secondary amines, showed beta-adrenoceptor stimulating activity. Another compounds, M-8, an aminotetralin that is a secondary amine, produced alpha and beta adrenoceptor stimulating activity. The beta-adrenoceptor stimulating activities of M-8 and JOD-176 showed more specificity for beta2-adrenoceptors than for beta1-adrenoceptors."}
{"id": "PMID:11758", "title": "Appetite stimulant activity of 3-carboxy-10,11-dihydrocyproheptadine.", "content": "The orexigenic and ancillary pharmacologic properties of 3-carboxy-10,11-dihydrocyproheptadine (CDC) were compared to those of cyproheptadine. The threshold dose, 0.0312 mg/kg p.o., of CDC for increasing food intake in the cat is similar to that of cyproheptadine, but CDC has a broader effective dose range, extending to 8 mg/kg p.o., compared with 1 mg/kg p.o. for cyproheptadine. Using an increase in food consumption of 20% or more as the criterion of a positive response, the dose effective in 50% of the animals was 0.35 mg/kg p.o. for both CDC and cyproheptadine. Both CDC and cyproheptadine possess a long duration of appetite-stimulant action, exceeding 18 hr following 0.5 mg/kg p.o. The ancillary pharmacologic properties of CDC are considerably reduced over those of cyproheptadine, except for antihistaminic activity, CDC being about two times more potent (protection against lethality in guinea-pigs exposed to an aeosol of histamine). As an anticholinergic in mice, CDC is greater than thirteen times less active than cyproheptadine as a mydriatic agent and greater than forty-two times less potent as an antagonist of oxotremorine-induced tremors. CDC retains only about 1/25 of the antiserotonin potency of the parent compound (inhibition of serotonin-elicited edema in the rat paw and 5-hydroxytryptophan provoked head twitch in rats). CDC reduced locomotor activity in rats to a significantly lesser degree than cyproheptadine. CDC thus is a more selective agent for the therapy of anorexia.", "contents": "Appetite stimulant activity of 3-carboxy-10,11-dihydrocyproheptadine. The orexigenic and ancillary pharmacologic properties of 3-carboxy-10,11-dihydrocyproheptadine (CDC) were compared to those of cyproheptadine. The threshold dose, 0.0312 mg/kg p.o., of CDC for increasing food intake in the cat is similar to that of cyproheptadine, but CDC has a broader effective dose range, extending to 8 mg/kg p.o., compared with 1 mg/kg p.o. for cyproheptadine. Using an increase in food consumption of 20% or more as the criterion of a positive response, the dose effective in 50% of the animals was 0.35 mg/kg p.o. for both CDC and cyproheptadine. Both CDC and cyproheptadine possess a long duration of appetite-stimulant action, exceeding 18 hr following 0.5 mg/kg p.o. The ancillary pharmacologic properties of CDC are considerably reduced over those of cyproheptadine, except for antihistaminic activity, CDC being about two times more potent (protection against lethality in guinea-pigs exposed to an aeosol of histamine). As an anticholinergic in mice, CDC is greater than thirteen times less active than cyproheptadine as a mydriatic agent and greater than forty-two times less potent as an antagonist of oxotremorine-induced tremors. CDC retains only about 1/25 of the antiserotonin potency of the parent compound (inhibition of serotonin-elicited edema in the rat paw and 5-hydroxytryptophan provoked head twitch in rats). CDC reduced locomotor activity in rats to a significantly lesser degree than cyproheptadine. CDC thus is a more selective agent for the therapy of anorexia."}
{"id": "PMID:11759", "title": "Spectral density analysis of the effects of barbiturates and benzodiazepines on the electrocorticogram of the squirrel monkey.", "content": "The effects of pentobarbital and diazepam were compared in a series of tests in squirrel monkeys; the effects of phenobarbital and flurazepam were compared in a second series. Observations were made of gross behavior and on the ECoG; the latter was analyzed by the spectral density technique. The two barbiturates induced sedation,which was occasionally so deep that the monkeys could not be readily aroused. The benzodiazepines induced sedation in some monkeys, but others showed signs of restlessness. The ECoG showed general slowing with the barbiturates, whereas the benzodiazepines produced mixed fast and slow patterns. Spectral density analysis showed that pentobarbital increased activity at frequencies below 40 Hz, with the largest increases occurring below 8 Hz. Phenobarbital increased activity below 8 Hz, but differed from pentobarbital by decreasing activity above 13 Hz. The benzodiazepines increased activity below 8 Hz, decreased it between 8 and 20 Hz, and increased it between 20 and 50 Hz.", "contents": "Spectral density analysis of the effects of barbiturates and benzodiazepines on the electrocorticogram of the squirrel monkey. The effects of pentobarbital and diazepam were compared in a series of tests in squirrel monkeys; the effects of phenobarbital and flurazepam were compared in a second series. Observations were made of gross behavior and on the ECoG; the latter was analyzed by the spectral density technique. The two barbiturates induced sedation,which was occasionally so deep that the monkeys could not be readily aroused. The benzodiazepines induced sedation in some monkeys, but others showed signs of restlessness. The ECoG showed general slowing with the barbiturates, whereas the benzodiazepines produced mixed fast and slow patterns. Spectral density analysis showed that pentobarbital increased activity at frequencies below 40 Hz, with the largest increases occurring below 8 Hz. Phenobarbital increased activity below 8 Hz, but differed from pentobarbital by decreasing activity above 13 Hz. The benzodiazepines increased activity below 8 Hz, decreased it between 8 and 20 Hz, and increased it between 20 and 50 Hz."}
{"id": "PMID:11760", "title": "Very high dose fluphenazine decanoate: a controlled trial in chronic schizophrenia.", "content": "In a double-blind trial of six months' duration, a very high dose (VHD) regimen of fluphenazine decanoate (250 mg weekly) was compared with a standard dose (SD) regimen (12.5 mg weekly) in 50 chronic schizophrenic patients. The rating scales used included the Brief Psychiatric Rating Scale and the Wing Ward Behavior Scale. Both treatment groups improved during the trial, but there was no significant difference between them. The VHD regimen, however, exerted better control of the psychosis in that it had fewer patient dropouts and fewer \"additional treatments\" prescribed. Some of the patients receiving standard doses were probably not receiving adequate antipsychotic drug dosage. No predictors of clinical response could be defined. Extrapyramidal side effects were not significantly higher in the VHD group.", "contents": "Very high dose fluphenazine decanoate: a controlled trial in chronic schizophrenia. In a double-blind trial of six months' duration, a very high dose (VHD) regimen of fluphenazine decanoate (250 mg weekly) was compared with a standard dose (SD) regimen (12.5 mg weekly) in 50 chronic schizophrenic patients. The rating scales used included the Brief Psychiatric Rating Scale and the Wing Ward Behavior Scale. Both treatment groups improved during the trial, but there was no significant difference between them. The VHD regimen, however, exerted better control of the psychosis in that it had fewer patient dropouts and fewer \"additional treatments\" prescribed. Some of the patients receiving standard doses were probably not receiving adequate antipsychotic drug dosage. No predictors of clinical response could be defined. Extrapyramidal side effects were not significantly higher in the VHD group."}
{"id": "PMID:11761", "title": "Effect of adrenergic blockade on gastric secretion altered by catecholamines in rats.", "content": "The effect of adrenergic blockade on gastric secretion altered by catecholamines was studied for 4 hr after injection in rats with chronic gastric fistulas. The alpha-adrenergic blockers phenoxybenzamine and phentolamine significantly inhibited the basal secretion of HCl and pepsin. Blockade of the beta-adrenergic receptors with propranolol did not change this secretion. Practolol in small doses slightly increased and in larger doses inhibited HCl out-put. Of the catecholamines, adrenaline and dopamine most markedly reduced HCl and pepsin secretion, while noradrenaline and isoprenaline had a weaker effect. Neither alpha- nor beta-adrenergic blockers prevented the inhibitory action of the catecholamines employed, but intensified the depression of the gastric secretion provoked by them. Adrenergic blockers inhibited secretion after catecholamines as well as basal secretion. This indicates that these two antagonistic groups of compounds act independently on the mechanism controlling gastric secretion. It is unlikely that this takes place indirectly through changes in the blood supply of the gastric mucosa.", "contents": "Effect of adrenergic blockade on gastric secretion altered by catecholamines in rats. The effect of adrenergic blockade on gastric secretion altered by catecholamines was studied for 4 hr after injection in rats with chronic gastric fistulas. The alpha-adrenergic blockers phenoxybenzamine and phentolamine significantly inhibited the basal secretion of HCl and pepsin. Blockade of the beta-adrenergic receptors with propranolol did not change this secretion. Practolol in small doses slightly increased and in larger doses inhibited HCl out-put. Of the catecholamines, adrenaline and dopamine most markedly reduced HCl and pepsin secretion, while noradrenaline and isoprenaline had a weaker effect. Neither alpha- nor beta-adrenergic blockers prevented the inhibitory action of the catecholamines employed, but intensified the depression of the gastric secretion provoked by them. Adrenergic blockers inhibited secretion after catecholamines as well as basal secretion. This indicates that these two antagonistic groups of compounds act independently on the mechanism controlling gastric secretion. It is unlikely that this takes place indirectly through changes in the blood supply of the gastric mucosa."}
{"id": "PMID:11762", "title": "Fluctuation in activity of the molecular forms of cellular DNA polymerase during infection by SV40.", "content": "Infection of BSC-1 cells by SV40 brings about an increase of 7--11-fold in DNA polymerase activity, found in the nuclei and cytoplasm, respectively. The overall ratio between activites of DNA polymerase beta (3.1S) and DNA polymerase alpha (5.5S) remains fairly constant throughout infection. However,there is a large increase in DNA polymerase alpha2 (7.1S) in the cytoplasm, and its appearance in the nuclei late in infection. The addition of 1 M NaCl to infected cytoplasm,causes an aggregation of DNA polymerase alpha into a higher sedimenting form (9.8S), termed DNA polymerase alpha3. DNA polymerase alpha1, alpha2 and alpha3 are different molecular forms of the same enzyme, as can be seen by their similar inhibition by N-ethyl-maleimide, heparin and NaCl. However, this new activity, alpha3, is stimulated by dithiothreitol to a greater extent at pH 9.30 than at pH 7.94. The conformational changes induced in DNA polymerase and its increase in activity during infection with SV40 are discussed.", "contents": "Fluctuation in activity of the molecular forms of cellular DNA polymerase during infection by SV40. Infection of BSC-1 cells by SV40 brings about an increase of 7--11-fold in DNA polymerase activity, found in the nuclei and cytoplasm, respectively. The overall ratio between activites of DNA polymerase beta (3.1S) and DNA polymerase alpha (5.5S) remains fairly constant throughout infection. However,there is a large increase in DNA polymerase alpha2 (7.1S) in the cytoplasm, and its appearance in the nuclei late in infection. The addition of 1 M NaCl to infected cytoplasm,causes an aggregation of DNA polymerase alpha into a higher sedimenting form (9.8S), termed DNA polymerase alpha3. DNA polymerase alpha1, alpha2 and alpha3 are different molecular forms of the same enzyme, as can be seen by their similar inhibition by N-ethyl-maleimide, heparin and NaCl. However, this new activity, alpha3, is stimulated by dithiothreitol to a greater extent at pH 9.30 than at pH 7.94. The conformational changes induced in DNA polymerase and its increase in activity during infection with SV40 are discussed."}
{"id": "PMID:11763", "title": "pH mediated inhibition of the cell to cell spread of herpes simplex virus infection.", "content": "The relationships between the environmental pH and the replication and spread of herps simplex virus (HSV) infection in rabbit skin (RS) cell cultures was studies. Relative to the plaque formation at pH7.0, incubation of RS cells with medium adjusted to pH 6.6 resulted in a 50 to 70 per cent decrement in plaque number. The addition of overlay media adjusted to pH 6.0 or 6.3 precluded HSV plaque formation. Select HSV-1 (type 1) and HSV (type 2) strains readily survived a 3 day incubation with medium adjusted to pH 6.3 as demonstrated by plaque production following a medium shift to pH 7.0. Rs cells incubated with medium at pH 6.3 did not replicate. The survival of RS cells incubated for 3 days with medium adjusted to pH 6.3 was demonstrated by renewed cell proliferation following a medium change from pH 6.3 to 7.0. The progeny virus yields of two HSV strains replicating in RS cells incubated with medium adjusted to pH 6.3 or 7.0 were equivalent at 24 or 48 hours post infection and were indicative of a productive infection. The inhibition of HSV plaque formation at pH 6.3 was not due to an alteration of cell receptors but was the result of an inhibition in the cell to cell spread of the virus. These results are discussed with regard to the possibility that the decline in pH associated with the inflammatory response may serve as a host defense against HSV infections.", "contents": "pH mediated inhibition of the cell to cell spread of herpes simplex virus infection. The relationships between the environmental pH and the replication and spread of herps simplex virus (HSV) infection in rabbit skin (RS) cell cultures was studies. Relative to the plaque formation at pH7.0, incubation of RS cells with medium adjusted to pH 6.6 resulted in a 50 to 70 per cent decrement in plaque number. The addition of overlay media adjusted to pH 6.0 or 6.3 precluded HSV plaque formation. Select HSV-1 (type 1) and HSV (type 2) strains readily survived a 3 day incubation with medium adjusted to pH 6.3 as demonstrated by plaque production following a medium shift to pH 7.0. Rs cells incubated with medium at pH 6.3 did not replicate. The survival of RS cells incubated for 3 days with medium adjusted to pH 6.3 was demonstrated by renewed cell proliferation following a medium change from pH 6.3 to 7.0. The progeny virus yields of two HSV strains replicating in RS cells incubated with medium adjusted to pH 6.3 or 7.0 were equivalent at 24 or 48 hours post infection and were indicative of a productive infection. The inhibition of HSV plaque formation at pH 6.3 was not due to an alteration of cell receptors but was the result of an inhibition in the cell to cell spread of the virus. These results are discussed with regard to the possibility that the decline in pH associated with the inflammatory response may serve as a host defense against HSV infections."}
{"id": "PMID:11764", "title": "The infection of cucumber mesophyll protoplasts with tobacco mosaic virus.", "content": "Protoplasts from the first leaf mesophyll of cucumber plants were isolated by an 18 hours combined petinase/cellulase treatment. Conditions favouring the infection of these protoplasts with tobacco mosaic virus (TMV), and the accumulation of infective virus up to 96 hours after inoculation have been studied. Infection of approximately 5--10 per cent of the protoplats, revealed by indirect fluorescent antibody staining, was achieved by pre-treatment of the cells in 0.01 M citrate-buffered mannitol (CBM), pH 5.2 with 2 mug/ml poly-L-ornithine followed by centrifugation and direct resuspension of the cells in the same mixture together with 2 to 4 mug/ml TMV. Higher concentrations of the polycation and buffer were toxic to the protoplasts. Under the best conditions, virus yields of approximately 10-20 mug TMV/10(6) protoplasts were attained, while after 72 hours incubation, significant amounts of virus could often be recovered from the incubation medium. Addition of actinomycin D to cultures of protoplasts 2 hours post-inoculation partially inhibited development of infectivity.", "contents": "The infection of cucumber mesophyll protoplasts with tobacco mosaic virus. Protoplasts from the first leaf mesophyll of cucumber plants were isolated by an 18 hours combined petinase/cellulase treatment. Conditions favouring the infection of these protoplasts with tobacco mosaic virus (TMV), and the accumulation of infective virus up to 96 hours after inoculation have been studied. Infection of approximately 5--10 per cent of the protoplats, revealed by indirect fluorescent antibody staining, was achieved by pre-treatment of the cells in 0.01 M citrate-buffered mannitol (CBM), pH 5.2 with 2 mug/ml poly-L-ornithine followed by centrifugation and direct resuspension of the cells in the same mixture together with 2 to 4 mug/ml TMV. Higher concentrations of the polycation and buffer were toxic to the protoplasts. Under the best conditions, virus yields of approximately 10-20 mug TMV/10(6) protoplasts were attained, while after 72 hours incubation, significant amounts of virus could often be recovered from the incubation medium. Addition of actinomycin D to cultures of protoplasts 2 hours post-inoculation partially inhibited development of infectivity."}
{"id": "PMID:11765", "title": "The growth of respiratory syncytial virus in organ cultures of bovine foetal trachea.", "content": "Respiratory syncytial (RS) virus grown in organ cultures of bovine foetal trachea at 37 degrees C and pH 7.2 reached maximum titres of up to 1 X 10(5) PFU/ml between 11 and 21 days after inoculation. Virus yield was increased three fold by incubation at 33 degrees C, but depressed by the addition of RS virus antiserum, with or without bovine complement, or by the addition of alveolar macrophages. Variation in pH or the concentration of foetal calf serum and magnesium chloride did not affect the virus yield. Virus growth did not affect ciliary activity of the cultures. Histological changes involved slight flattening of the epithelium and the appearance of phloxinophilic inclusion bodies. Fluorescent antibody staining showed more virus antigen in the peri-tracheal connective tissue than in the ciliated epithelium. The presence of non-cytopathic mucosal disease (MD) virus in RS virus infected organ cultures slightly depressed RS virus growth but did not influence ciliary activity. These in vitro experiments suggest that the tracheal epithelium may not be an important target in the pathogenesis of RS virus infection in vivo.", "contents": "The growth of respiratory syncytial virus in organ cultures of bovine foetal trachea. Respiratory syncytial (RS) virus grown in organ cultures of bovine foetal trachea at 37 degrees C and pH 7.2 reached maximum titres of up to 1 X 10(5) PFU/ml between 11 and 21 days after inoculation. Virus yield was increased three fold by incubation at 33 degrees C, but depressed by the addition of RS virus antiserum, with or without bovine complement, or by the addition of alveolar macrophages. Variation in pH or the concentration of foetal calf serum and magnesium chloride did not affect the virus yield. Virus growth did not affect ciliary activity of the cultures. Histological changes involved slight flattening of the epithelium and the appearance of phloxinophilic inclusion bodies. Fluorescent antibody staining showed more virus antigen in the peri-tracheal connective tissue than in the ciliated epithelium. The presence of non-cytopathic mucosal disease (MD) virus in RS virus infected organ cultures slightly depressed RS virus growth but did not influence ciliary activity. These in vitro experiments suggest that the tracheal epithelium may not be an important target in the pathogenesis of RS virus infection in vivo."}
{"id": "PMID:11767", "title": "Epilepsy.", "content": "Epilepsy is a common disorder affecting approximately one in every two hundred people, from all walks of life, and presenting in addition to the seizure disorder itself, varying social, psychological and economic problems. A simple classification of epilepsy is described, and the concept of 'seizure threshold' introduced. Having diagnosed epilepsy, the need for investigation to separate the symptomatic epilepsies from idiopathic epilepsy is stressed. Accurate diagnosis of seizure type ensures that optimal therapy can be offered. The various drugs used to control epilepsy are discussed, and comments on the general management of the patient are offered.", "contents": "Epilepsy. Epilepsy is a common disorder affecting approximately one in every two hundred people, from all walks of life, and presenting in addition to the seizure disorder itself, varying social, psychological and economic problems. A simple classification of epilepsy is described, and the concept of 'seizure threshold' introduced. Having diagnosed epilepsy, the need for investigation to separate the symptomatic epilepsies from idiopathic epilepsy is stressed. Accurate diagnosis of seizure type ensures that optimal therapy can be offered. The various drugs used to control epilepsy are discussed, and comments on the general management of the patient are offered."}
{"id": "PMID:11771", "title": "Rate of elemental sulfur oxidation in some soils of Egypt as affected by the salinity level, moisture, texture, temperature and inoculation.", "content": "1. The level of soil moisture most favourable to the oxidation of elemental sulfur was found to be around the field moisture capacity; the oxidation rate decreased at lower and higher moisture levels. 2. The rate of oxidation increased with the clay content of the soils from sandy loam to clay loam. 3. Although S-oxidation could be found already at 10 degrees C, it increased markedly up to a maximum at 35 degrees C and then decreased again at higher temperatures. 4. Increasing the salt content of the soil (NaCl) reduced the rate of oxidation up to a concentration of 9 g salt/100 g soil; at a concentration of salt of 11 g/100 g soil no S-oxidation occurred. 5. Inoculation of the soil with Thiobacillus thiooxidans accelerated the S-oxidation, especially when organic matter was added. 6. In all experiments, S-oxidation was accompained by a decrease in pH.", "contents": "Rate of elemental sulfur oxidation in some soils of Egypt as affected by the salinity level, moisture, texture, temperature and inoculation. 1. The level of soil moisture most favourable to the oxidation of elemental sulfur was found to be around the field moisture capacity; the oxidation rate decreased at lower and higher moisture levels. 2. The rate of oxidation increased with the clay content of the soils from sandy loam to clay loam. 3. Although S-oxidation could be found already at 10 degrees C, it increased markedly up to a maximum at 35 degrees C and then decreased again at higher temperatures. 4. Increasing the salt content of the soil (NaCl) reduced the rate of oxidation up to a concentration of 9 g salt/100 g soil; at a concentration of salt of 11 g/100 g soil no S-oxidation occurred. 5. Inoculation of the soil with Thiobacillus thiooxidans accelerated the S-oxidation, especially when organic matter was added. 6. In all experiments, S-oxidation was accompained by a decrease in pH."}
{"id": "PMID:11772", "title": "Concentration of MgATP2- and other ions in solution. Calculation of the true concentrations of species present in mixtures of associating ions.", "content": "1. A simple method is described for calculating the free concentrations of all species in a mixture of several ionic components that associate at equilibrium to any extent and with any stoicheiometry. 2. It can readily be adapted to take account of species such as protons for which the free rather than the total concentrations are controlled. 3. It was applied to mixtures of adenine nucleotides, Mg2+ and other ions relevant to the study of glucokinase (EC 2.7.1.2), but the qualitative conclusions are not peculiar to this system. 4. ATP exists in a high and nearly constant proportion (about 80%) as MgATP2- in solutions in which the total MgCl2 concentration exceeds the total ATP concentration by 1-10 mM. 5. By contrast, the proportion of ATP present as MgATP2- varies greatly if the total MgCl2 and total ATP concentrations are varied in constant proportion.", "contents": "Concentration of MgATP2- and other ions in solution. Calculation of the true concentrations of species present in mixtures of associating ions. 1. A simple method is described for calculating the free concentrations of all species in a mixture of several ionic components that associate at equilibrium to any extent and with any stoicheiometry. 2. It can readily be adapted to take account of species such as protons for which the free rather than the total concentrations are controlled. 3. It was applied to mixtures of adenine nucleotides, Mg2+ and other ions relevant to the study of glucokinase (EC 2.7.1.2), but the qualitative conclusions are not peculiar to this system. 4. ATP exists in a high and nearly constant proportion (about 80%) as MgATP2- in solutions in which the total MgCl2 concentration exceeds the total ATP concentration by 1-10 mM. 5. By contrast, the proportion of ATP present as MgATP2- varies greatly if the total MgCl2 and total ATP concentrations are varied in constant proportion."}
{"id": "PMID:11773", "title": "Purification and properties of arylsulphatase A from rabbit testis.", "content": "Rabbit testis arylsulphatase A was purified 140-fold with a recovery of 20% from detergent extracts of an acetone-dried powder by using DE-52 cellulose column chromatography, gel filtration on Sephadex G-200 and preparative isoelectric focusing. The purified enzyme showed one major band with one minor contaminant on electrophoresis in a 7.5% (w/v) polyacrylamide gel at pH8.3. On sodiumdodecyl sulphate/polyacrylamidegel electrophoresis, a single major band was observed with minor contaminants. The final preparation of enzyme was free from general proteolytic, esterase, hyaluronidase, beta-glucuronidase and beta-galactosidase activities. Rabbit testicular arylsulphatase A exists as a dimer of mol.wt. 110000 at pH7.1. At pH5.0 the enzyme is a tetramer of mol.wt. 220000. Arylsulphatase A appears to consist of two identical subunits of mol.wt. 55000 each. The highly purified enzyme has pI4.6. The enzyme hydrolyses p-nitrocatechol sulphate with Km and Vmax, of 4.1 mM and 80nmol/min respectively, but has no activity toward p-nitrophenyl sulphate. The pH optimum of the enzyme varies with the incubation time. By applying Sephacex G-200 chromatography and preparative isoelectric focusing, one form of enzyme was obtained. The enzyme has properites common to arylsulphatase A of other sources with respect to the anomalous time-activity relationship, pI, inhibition by PO42-, SO32- and Ag+ ions and substrate affinity to p-nitrocatechol sulphate. However, the enzyme shows the temperature optimum of arylsulphatase B of other species.", "contents": "Purification and properties of arylsulphatase A from rabbit testis. Rabbit testis arylsulphatase A was purified 140-fold with a recovery of 20% from detergent extracts of an acetone-dried powder by using DE-52 cellulose column chromatography, gel filtration on Sephadex G-200 and preparative isoelectric focusing. The purified enzyme showed one major band with one minor contaminant on electrophoresis in a 7.5% (w/v) polyacrylamide gel at pH8.3. On sodiumdodecyl sulphate/polyacrylamidegel electrophoresis, a single major band was observed with minor contaminants. The final preparation of enzyme was free from general proteolytic, esterase, hyaluronidase, beta-glucuronidase and beta-galactosidase activities. Rabbit testicular arylsulphatase A exists as a dimer of mol.wt. 110000 at pH7.1. At pH5.0 the enzyme is a tetramer of mol.wt. 220000. Arylsulphatase A appears to consist of two identical subunits of mol.wt. 55000 each. The highly purified enzyme has pI4.6. The enzyme hydrolyses p-nitrocatechol sulphate with Km and Vmax, of 4.1 mM and 80nmol/min respectively, but has no activity toward p-nitrophenyl sulphate. The pH optimum of the enzyme varies with the incubation time. By applying Sephacex G-200 chromatography and preparative isoelectric focusing, one form of enzyme was obtained. The enzyme has properites common to arylsulphatase A of other sources with respect to the anomalous time-activity relationship, pI, inhibition by PO42-, SO32- and Ag+ ions and substrate affinity to p-nitrocatechol sulphate. However, the enzyme shows the temperature optimum of arylsulphatase B of other species."}
{"id": "PMID:11774", "title": "Application of a spectrophotometric method to the determination of the composition of oligonucleotides obtained from cysteine transfer ribonucleic acid.", "content": "1. The applications of methods for determining the composition of oligonucleotides from u.v.-absorption spectra is described. 2. In the first method absorbances at selected wave-lengths were read from the spectra of oligonucleotides in solution in 7 M-urea which had been recorded at acid and alkaline pH values. 3. In the second method absorbances were sampled automatically at regular time-intervals during scans at acid and alkaline pH of each spectrum, converted into digital signals and recorded on paper take for computer processing. The holmium spectrum in the region of the holmium peak at 333.7 nm was superimposed on each nucleotide spectrum. The position of this peak maximum was used as a standard reference point in the computer-based analysis. 4. By using either method the composition was calculated by a least-squares procedure by using a library of values for five standard nucelotides obtained in a similar manner. 5. The methods gave satisfactory compositions for mixtures of mononucleotides as well as for five dinucleoside monophosphates. 6. Methods of minimizing the effects on the nucleotide composition of spectural changes due to base stacking are discussed. 7. The compositions of some oligonucleotides obtained during an investigation of the nucleotide sequence of tRNA (Cys) were determined and agreed with the sequences found by other methods.", "contents": "Application of a spectrophotometric method to the determination of the composition of oligonucleotides obtained from cysteine transfer ribonucleic acid. 1. The applications of methods for determining the composition of oligonucleotides from u.v.-absorption spectra is described. 2. In the first method absorbances at selected wave-lengths were read from the spectra of oligonucleotides in solution in 7 M-urea which had been recorded at acid and alkaline pH values. 3. In the second method absorbances were sampled automatically at regular time-intervals during scans at acid and alkaline pH of each spectrum, converted into digital signals and recorded on paper take for computer processing. The holmium spectrum in the region of the holmium peak at 333.7 nm was superimposed on each nucleotide spectrum. The position of this peak maximum was used as a standard reference point in the computer-based analysis. 4. By using either method the composition was calculated by a least-squares procedure by using a library of values for five standard nucelotides obtained in a similar manner. 5. The methods gave satisfactory compositions for mixtures of mononucleotides as well as for five dinucleoside monophosphates. 6. Methods of minimizing the effects on the nucleotide composition of spectural changes due to base stacking are discussed. 7. The compositions of some oligonucleotides obtained during an investigation of the nucleotide sequence of tRNA (Cys) were determined and agreed with the sequences found by other methods."}
{"id": "PMID:11775", "title": "Unmasking of histone amino groups in chromatin at high pH.", "content": "The reactivity of the amino groups of histones in chromatin towards acetic anhydride was determined as a function of pH. In the pH range 7-10 the vast majority of amino groups in all five histones are buried. However, at higher pH values some of the histone amino groups become exposed, and the higher the lysine:arginine ratio for the histone the greater was the degree of unmasking observed. At pH 11.8 histone I appears to be completely dissociated, histones IIB1 and IIb2 have approx. 55% of the amino groups unmasked, and histones III and IV have approx. 25% of the amino groups unmasked.", "contents": "Unmasking of histone amino groups in chromatin at high pH. The reactivity of the amino groups of histones in chromatin towards acetic anhydride was determined as a function of pH. In the pH range 7-10 the vast majority of amino groups in all five histones are buried. However, at higher pH values some of the histone amino groups become exposed, and the higher the lysine:arginine ratio for the histone the greater was the degree of unmasking observed. At pH 11.8 histone I appears to be completely dissociated, histones IIB1 and IIb2 have approx. 55% of the amino groups unmasked, and histones III and IV have approx. 25% of the amino groups unmasked."}
{"id": "PMID:11776", "title": "Isolation, characterization and oxygen equilibrium of an extracellular haemoglobin from Eunice aphroditois (Passas).", "content": "The extracellular haemoglobin from the polychaeta,Eunice aphroditois, existed as a mixture of a heavy major component (so20, w = 56.96 +/- 0.125) and a light minor component (so20, w = 10.00 +/- 0.13S), the latter probably being a dissociation product of the former. The molecular weight of the purified heavier component, as detetermined by sedimentation equilibrium, was 3.44 x 10(6) +/- 0.04x10(6). The molecule had the electron-microscopic appearance typical of annelid haemoglobins, consisting of a stack of two hexagonal plates, with dimensions 26.32 +/- 0.27 nm across the flats of the hexagon, height of stack 17.86 +/- 0.34 nm. The sugar composition is reported, and the isoelectric point was approx. pH7.8. The haem content was 2.31 +/- 0.01%, corresponding to a minimal mol.wt. of 26700. Detergent/gel electrophoresis revealed the presence of at least four bands with molecular weights in the range 14600-31000. Five N-terminal amino acids were found. In addition to the 10S component, which co-existed with the 57S component at all pH values in the range 4.0-10.6, at low pH values (less than pH.5.0) A 16S and a 1.9 S component were found. The absorption and circular-dichroic spectra are reported, and the alpha-helical content, calculated from the ellipticity at 222 nm, was about 40%. The molecule bound O2 co-operatively with a maximum value of the Hill coefficient, h, of 3.9. Over the pH range 7.0-8.0 there was a positive Bohr effect.", "contents": "Isolation, characterization and oxygen equilibrium of an extracellular haemoglobin from Eunice aphroditois (Passas). The extracellular haemoglobin from the polychaeta,Eunice aphroditois, existed as a mixture of a heavy major component (so20, w = 56.96 +/- 0.125) and a light minor component (so20, w = 10.00 +/- 0.13S), the latter probably being a dissociation product of the former. The molecular weight of the purified heavier component, as detetermined by sedimentation equilibrium, was 3.44 x 10(6) +/- 0.04x10(6). The molecule had the electron-microscopic appearance typical of annelid haemoglobins, consisting of a stack of two hexagonal plates, with dimensions 26.32 +/- 0.27 nm across the flats of the hexagon, height of stack 17.86 +/- 0.34 nm. The sugar composition is reported, and the isoelectric point was approx. pH7.8. The haem content was 2.31 +/- 0.01%, corresponding to a minimal mol.wt. of 26700. Detergent/gel electrophoresis revealed the presence of at least four bands with molecular weights in the range 14600-31000. Five N-terminal amino acids were found. In addition to the 10S component, which co-existed with the 57S component at all pH values in the range 4.0-10.6, at low pH values (less than pH.5.0) A 16S and a 1.9 S component were found. The absorption and circular-dichroic spectra are reported, and the alpha-helical content, calculated from the ellipticity at 222 nm, was about 40%. The molecule bound O2 co-operatively with a maximum value of the Hill coefficient, h, of 3.9. Over the pH range 7.0-8.0 there was a positive Bohr effect."}
{"id": "PMID:11777", "title": "Preparation of fully active ficin from Ficus glabrata by covalent chromatography and characterization of its active centre by using 2,2'-depyridyl disulphide as a reactivity probe.", "content": "1. Fully active ficin (EC 3.4.22.3) containing 1 mol of thiol with high reactivity towards 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) at pH4.5 per mol of protein was prepared from the dried latex of Ficus glabrata by covalent chromatography on a Sepharose-glutathione-2-pyridyl disulphide gel. 2. Ficin thus prepared is a mixture of ficins I-IV and ficin G, in which ficins II and III predominate. The various ficins exhibit similar reactivity characteristics towards 2-Py-S-S-2-Py. 3. Use of 2-Py-S-S-2-Py as a reactivity probe demonstrates (a) that in ficin, as in papain (EC 3.4.22.2), the active-centre thiol and imidazole groups interact to provide a nucleophilic state at pH values of approx. 6 additional to the uncomplicated thiolate ion that predominates at pH values over 9, and (b) a structural difference between ficin and papain that leads to a much higher rate of reaction of 2-Py-S-S-2-Py with ficin than with papain at pH values 3-4. This difference is suggested to include a lack in ficin of a carboxyl group conformationally equivalent to that of aspartic acid-158 in papain. 4. The high electrophilicity of the 2-Py-S-S-2PyH+ monocation allows directly the detection of the exposure of the buried thiol group of ficin at pH values below 4.", "contents": "Preparation of fully active ficin from Ficus glabrata by covalent chromatography and characterization of its active centre by using 2,2'-depyridyl disulphide as a reactivity probe. 1. Fully active ficin (EC 3.4.22.3) containing 1 mol of thiol with high reactivity towards 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) at pH4.5 per mol of protein was prepared from the dried latex of Ficus glabrata by covalent chromatography on a Sepharose-glutathione-2-pyridyl disulphide gel. 2. Ficin thus prepared is a mixture of ficins I-IV and ficin G, in which ficins II and III predominate. The various ficins exhibit similar reactivity characteristics towards 2-Py-S-S-2-Py. 3. Use of 2-Py-S-S-2-Py as a reactivity probe demonstrates (a) that in ficin, as in papain (EC 3.4.22.2), the active-centre thiol and imidazole groups interact to provide a nucleophilic state at pH values of approx. 6 additional to the uncomplicated thiolate ion that predominates at pH values over 9, and (b) a structural difference between ficin and papain that leads to a much higher rate of reaction of 2-Py-S-S-2-Py with ficin than with papain at pH values 3-4. This difference is suggested to include a lack in ficin of a carboxyl group conformationally equivalent to that of aspartic acid-158 in papain. 4. The high electrophilicity of the 2-Py-S-S-2PyH+ monocation allows directly the detection of the exposure of the buried thiol group of ficin at pH values below 4."}
{"id": "PMID:11778", "title": "4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole as a reactivity probe for the investigation of the thiol proteinases. evidence that ficin and bromelain may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain.", "content": "1. 4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride) was used as a reactivity probe to characterize the active centres of papin (EC 3.4.22.2), ficin (EC 3.4.22.3) and bromelain (EC 3.4.22.4). 2. In the pH range 0-8 Nbd chloride probably exists mainly as a monocation, possibly with the proton located on N-1 of the oxadiazole ring. 3. Spectroscopic evidence is presented for the intermediacy of Meisenheimer-type adducts in the reaction of Nbd chloride with nucleophiles. 4. The pH-dependence of the second-order rate constants (k) of the reactions of the three enzymes with Nbd chloride was determined at 25 degrees C, I = 0.1 mol/litre in 6.7% (v/v) ethanol in the pH range 2.5-5, where, at least for papain and ficin, the reactions occur specifically with their active-centre thiol groups. The pH-k profile for the papain reaction is bell-shaped (pKaI = 3.24, pKaII = 3.44 and k = 86M(-1)-s(-1), whereas that for ficin is sigmoidal (pKa = 3.6, k = 0.36M(-1)-s(-1), the rate increasing with increasing pH. The profile for the bromelain reaction appears to resemble that for the ficin reaction, but is complicated by amino-group labelling. 5. The bell-shaped profile of the papain reaction is considered to arise from the reaction of the thiolate ion of cysteine-25, maintained in acidic media by interaction with the side chain of histidine-159, with the Nbd chloride monocation hydrogen-bonded at its nitro group to the un-ionized form of the carboxyl group of aspartic acid-158. The lack of acid catalysis in the corresponding reactions of ficin and probably of bromelain suggests that these enzymes may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain. The possible consequences of this for the catalytic sites of these enzymes is discussed.", "contents": "4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole as a reactivity probe for the investigation of the thiol proteinases. evidence that ficin and bromelain may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain. 1. 4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride) was used as a reactivity probe to characterize the active centres of papin (EC 3.4.22.2), ficin (EC 3.4.22.3) and bromelain (EC 3.4.22.4). 2. In the pH range 0-8 Nbd chloride probably exists mainly as a monocation, possibly with the proton located on N-1 of the oxadiazole ring. 3. Spectroscopic evidence is presented for the intermediacy of Meisenheimer-type adducts in the reaction of Nbd chloride with nucleophiles. 4. The pH-dependence of the second-order rate constants (k) of the reactions of the three enzymes with Nbd chloride was determined at 25 degrees C, I = 0.1 mol/litre in 6.7% (v/v) ethanol in the pH range 2.5-5, where, at least for papain and ficin, the reactions occur specifically with their active-centre thiol groups. The pH-k profile for the papain reaction is bell-shaped (pKaI = 3.24, pKaII = 3.44 and k = 86M(-1)-s(-1), whereas that for ficin is sigmoidal (pKa = 3.6, k = 0.36M(-1)-s(-1), the rate increasing with increasing pH. The profile for the bromelain reaction appears to resemble that for the ficin reaction, but is complicated by amino-group labelling. 5. The bell-shaped profile of the papain reaction is considered to arise from the reaction of the thiolate ion of cysteine-25, maintained in acidic media by interaction with the side chain of histidine-159, with the Nbd chloride monocation hydrogen-bonded at its nitro group to the un-ionized form of the carboxyl group of aspartic acid-158. The lack of acid catalysis in the corresponding reactions of ficin and probably of bromelain suggests that these enzymes may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain. The possible consequences of this for the catalytic sites of these enzymes is discussed."}
{"id": "PMID:11779", "title": "A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe.", "content": "1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 +/- 1.47 kat/kg, Km = 3.32 +/- 0.05 mM; kcat. = 2.15 X 10(4) +/- 0.05 X 10(4)s-1 at pH7.0 and 38 degrees C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin. 11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and epsilon280 = 2.84 X 10(5) litre-mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six 'essential' thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25 degrees C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 X 10(4)M-1-s-1 and (b) pKa = 8.1, k = 8.05 X 10(2)M-1-s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 X 10(2)M-1-s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases an or equal to approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the 'essential' thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.", "contents": "A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe. 1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 +/- 1.47 kat/kg, Km = 3.32 +/- 0.05 mM; kcat. = 2.15 X 10(4) +/- 0.05 X 10(4)s-1 at pH7.0 and 38 degrees C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin. 11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and epsilon280 = 2.84 X 10(5) litre-mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six 'essential' thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25 degrees C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 X 10(4)M-1-s-1 and (b) pKa = 8.1, k = 8.05 X 10(2)M-1-s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 X 10(2)M-1-s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases an or equal to approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the 'essential' thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed."}
{"id": "PMID:11780", "title": "Isolation and characterization of two sequence-specific endonucleases from Anabaena variabilis.", "content": "Two endonucleases, AvaI and AvaII, were isolated from Anabaena variabilis on the basis of their ability to make a limited number of breaks at specific points in bacteriophage lambda DNA. Neither enzyme has cofactor requirements beyond Mg2+. Endonuclease AvaI makes eight breaks in the phage lambda chromosome at which the 5'-terminal sequence is pPy-C-G-N. AvaII endonuclease cuts phage lambda DNA more extensively, yielding fragments with the 5'-terminal sequence G-T-C-N or G-A-C-N. Neither enzyme generates cohesive ends.", "contents": "Isolation and characterization of two sequence-specific endonucleases from Anabaena variabilis. Two endonucleases, AvaI and AvaII, were isolated from Anabaena variabilis on the basis of their ability to make a limited number of breaks at specific points in bacteriophage lambda DNA. Neither enzyme has cofactor requirements beyond Mg2+. Endonuclease AvaI makes eight breaks in the phage lambda chromosome at which the 5'-terminal sequence is pPy-C-G-N. AvaII endonuclease cuts phage lambda DNA more extensively, yielding fragments with the 5'-terminal sequence G-T-C-N or G-A-C-N. Neither enzyme generates cohesive ends."}
{"id": "PMID:11781", "title": "Absorption of antisera for studies on specific enzyme turnover.", "content": "Antisera were raised to acetyl-CoA carboxylase and 6-phosphogluconate dehydrogenase from mammary glands of lactating rabbits, and cytochrome oxidase from rat liver. The enzymes were all highly purified but gave rise to multispecific antisera when tested against tissue extracts. Absorption procedures were devised to free the antisera of contaminating antibodies. Antisera to acetyl-CoA carboxylase and cytochrome oxidase were absorbed with fractions discarded during enzyme purification. The antiserum to 6-phospho-gluconate dehydrogenase was absorbed with a tissue extract from an early stage in mammary-gland differentiation. Monospecific antisera are essential for enzyme turnover studies and therefore antisera should be extensively tested and absorbed before use. A general procedure for the absorption of antisera to purified enzymes has been devised on the basis of accepted principles of antisera absorption.", "contents": "Absorption of antisera for studies on specific enzyme turnover. Antisera were raised to acetyl-CoA carboxylase and 6-phosphogluconate dehydrogenase from mammary glands of lactating rabbits, and cytochrome oxidase from rat liver. The enzymes were all highly purified but gave rise to multispecific antisera when tested against tissue extracts. Absorption procedures were devised to free the antisera of contaminating antibodies. Antisera to acetyl-CoA carboxylase and cytochrome oxidase were absorbed with fractions discarded during enzyme purification. The antiserum to 6-phospho-gluconate dehydrogenase was absorbed with a tissue extract from an early stage in mammary-gland differentiation. Monospecific antisera are essential for enzyme turnover studies and therefore antisera should be extensively tested and absorbed before use. A general procedure for the absorption of antisera to purified enzymes has been devised on the basis of accepted principles of antisera absorption."}
{"id": "PMID:11782", "title": "The kinetics and mechanism of the recombination reaction between apomyoglobin and haemin.", "content": "A simple rapid-mixing technique is described which allows the recombination reaction between apomyoglobin and haemin to be studied within 0.3s of the splitting of myoglobin by dilute HCl. Evidence is presented that indicates that the recombination process occurs between folded 'native' apomyoglobin and monomeric haemin. Postulation of a one (or more)-intermediate recombination process, as suggested by other studies, is not necessary to explain the results. The effect, on the kinetics and mechanism of recombination, of the time of exposure to acid pH of the split myoglobin solution was investigated. The effect of temperature on the recombination kinetics was also studied.", "contents": "The kinetics and mechanism of the recombination reaction between apomyoglobin and haemin. A simple rapid-mixing technique is described which allows the recombination reaction between apomyoglobin and haemin to be studied within 0.3s of the splitting of myoglobin by dilute HCl. Evidence is presented that indicates that the recombination process occurs between folded 'native' apomyoglobin and monomeric haemin. Postulation of a one (or more)-intermediate recombination process, as suggested by other studies, is not necessary to explain the results. The effect, on the kinetics and mechanism of recombination, of the time of exposure to acid pH of the split myoglobin solution was investigated. The effect of temperature on the recombination kinetics was also studied."}
{"id": "PMID:11783", "title": "Thiol-protein disulphide oxidoreductases. Assay of microsomal membrane-bound glutathione-insulin transhydrogenase and comparison with protein disulphide-isomerase.", "content": "1. Inhibition of endogenous microsomal NADPH oxidase by CO enables membrane-bound glutathione-insulin transhydrogenase (EC 1.8.4.2) to be assayed conveniently by a linked assay involving NADPH and glutathione reductase (EC 1.6.4.2). 2. The specific activity of the enzyme in rat liver microsomal preparations is of the order of 1 nmol of oxidized glutathione formed/min per mg of membrane protein. 3. The specific activity of the enzyme is comparable in rough and smooth microsomal fractions, and the activity is not affected by treatment with EDTA and the removal of ribosomes from rough microsomal fractions. 4. Membrane-bound glutathione-insulin transhydrogenase is not affected by concentrations of deoxycholate up to 0.5%, whereas protein disulphide-isomerase (EC 5.3.4.1) is drastically inhibited. 5. On these grounds it is concluded that, in rat liver microsomal fractions, glutathione-insulin transhydrogenase and protein disulphide-isomerase activities are not both catalysed by a single enzyme species.", "contents": "Thiol-protein disulphide oxidoreductases. Assay of microsomal membrane-bound glutathione-insulin transhydrogenase and comparison with protein disulphide-isomerase. 1. Inhibition of endogenous microsomal NADPH oxidase by CO enables membrane-bound glutathione-insulin transhydrogenase (EC 1.8.4.2) to be assayed conveniently by a linked assay involving NADPH and glutathione reductase (EC 1.6.4.2). 2. The specific activity of the enzyme in rat liver microsomal preparations is of the order of 1 nmol of oxidized glutathione formed/min per mg of membrane protein. 3. The specific activity of the enzyme is comparable in rough and smooth microsomal fractions, and the activity is not affected by treatment with EDTA and the removal of ribosomes from rough microsomal fractions. 4. Membrane-bound glutathione-insulin transhydrogenase is not affected by concentrations of deoxycholate up to 0.5%, whereas protein disulphide-isomerase (EC 5.3.4.1) is drastically inhibited. 5. On these grounds it is concluded that, in rat liver microsomal fractions, glutathione-insulin transhydrogenase and protein disulphide-isomerase activities are not both catalysed by a single enzyme species."}
{"id": "PMID:11784", "title": "Adenosine 3':5'-cyclic monophosphate-binding proteins in bovine and rat tissues.", "content": "1. At least two classes of high-affinity cyclic AMP-binding proteins have been identified: those derived from cyclic AMP-dependent protein kinases (regulatory subunits) and those that bind a wide range of adenine analogues (adenine analogue-binding proteins). 2. In fresh-tissue extracts, regulatory subunits could be further subdivided into 'type I or 'type II' depending on whether they were derived from 'type I' or 'type II' protein kinase [see Corbin et al. (1975) J. Biol. Chem. 250, 218-225]. 3. The adenine analogue-binding protein was detected in crude tissue supernatant fractions of bovine and rat liver. It differed from the regulatory subunit of cyclic AMP-dependent protein kinase in many of its properties. Under the conditions of assay used, the protein accounted for about 45% of the binding of cyclic AMP to bovine liver supernatants. 4. The adenine analogue-binding protein from bovine liver was partially purified by DEAE-cellulose and Sepharose 6B chromatography. It had mol.wt. 185000 and was trypsin-sensitive. As shown by competition and direct binding experiments, it bound adenosine and AMP in addition to cyclic AMP. At intracellular concentrations of adenine nucleotides, binding of cyclic AMP was essentially completely inhibited in vitro. Adenosine binding was inhibited by only 30% under similar conditions. 5. Rat tissues were examined for the presence of the adenine analogue-binding protein, and, of those examined (adipose tissue, heart, brain, testis, kidney and liver), significant amounts were only found in the liver. The possible physiological role of the adenine analogue-binding protein is discussed. 6. Because the adenine analogue-binding protein or other cyclic AMP-binding proteins in tissues may be products of partial proteolysis of the regulatory subunit of cyclic AMP-dependent protein kinase, the effects of trypsin and aging on partially purified protein kinase and its regulatory subunit from bovine liver were investigated. In all studies, the effects of trypsin and aging were similar. 7. In fresh preparations, the cyclic AMP-dependent protein kinase had mol.wt. 150000. Trypsin treatment converted it into a form of mol.wt 79500. 8. The regulatory subunit of the protein kinase had mol.wt. 87000. It would reassociate with and inhibit the catalytic subunit of the enzyme. Trypsin treatment of the regulatory subunit produced a species of mol.wt. 35500 which bound cyclic AMP but did not reassociate with the catalytic subunit. Trypsin treatment of the protein kinase and dissociation of the product by cyclic AMP produced a regulatory subunit of mol.wt. 46500 which reassociated with the catalytic subunit. 9. These results may be explained by at least two trypsin-sensitive sites on the regulatory subunit. A model for the effects of trypsin is described.", "contents": "Adenosine 3':5'-cyclic monophosphate-binding proteins in bovine and rat tissues. 1. At least two classes of high-affinity cyclic AMP-binding proteins have been identified: those derived from cyclic AMP-dependent protein kinases (regulatory subunits) and those that bind a wide range of adenine analogues (adenine analogue-binding proteins). 2. In fresh-tissue extracts, regulatory subunits could be further subdivided into 'type I or 'type II' depending on whether they were derived from 'type I' or 'type II' protein kinase [see Corbin et al. (1975) J. Biol. Chem. 250, 218-225]. 3. The adenine analogue-binding protein was detected in crude tissue supernatant fractions of bovine and rat liver. It differed from the regulatory subunit of cyclic AMP-dependent protein kinase in many of its properties. Under the conditions of assay used, the protein accounted for about 45% of the binding of cyclic AMP to bovine liver supernatants. 4. The adenine analogue-binding protein from bovine liver was partially purified by DEAE-cellulose and Sepharose 6B chromatography. It had mol.wt. 185000 and was trypsin-sensitive. As shown by competition and direct binding experiments, it bound adenosine and AMP in addition to cyclic AMP. At intracellular concentrations of adenine nucleotides, binding of cyclic AMP was essentially completely inhibited in vitro. Adenosine binding was inhibited by only 30% under similar conditions. 5. Rat tissues were examined for the presence of the adenine analogue-binding protein, and, of those examined (adipose tissue, heart, brain, testis, kidney and liver), significant amounts were only found in the liver. The possible physiological role of the adenine analogue-binding protein is discussed. 6. Because the adenine analogue-binding protein or other cyclic AMP-binding proteins in tissues may be products of partial proteolysis of the regulatory subunit of cyclic AMP-dependent protein kinase, the effects of trypsin and aging on partially purified protein kinase and its regulatory subunit from bovine liver were investigated. In all studies, the effects of trypsin and aging were similar. 7. In fresh preparations, the cyclic AMP-dependent protein kinase had mol.wt. 150000. Trypsin treatment converted it into a form of mol.wt 79500. 8. The regulatory subunit of the protein kinase had mol.wt. 87000. It would reassociate with and inhibit the catalytic subunit of the enzyme. Trypsin treatment of the regulatory subunit produced a species of mol.wt. 35500 which bound cyclic AMP but did not reassociate with the catalytic subunit. Trypsin treatment of the protein kinase and dissociation of the product by cyclic AMP produced a regulatory subunit of mol.wt. 46500 which reassociated with the catalytic subunit. 9. These results may be explained by at least two trypsin-sensitive sites on the regulatory subunit. A model for the effects of trypsin is described."}
{"id": "PMID:11808", "title": "Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana.", "content": "The alkaloid 13-hydroxylupanine-2-pyrrolcarbonic acid ester (Hoe 933) from the Madagascan plant Cadia ellisiana has an hypotensive and antiarrhythmic effect. The hypotensive effect in dogs, monkeys, and rats anaesthetized with barbiturates reaches its maximum with 0.2 mg/kg i.v. However, the hypotensive effect is much weaker in conscious animals. The enteral absorption in the dog is good; an intraduodenal dose of only 0.5 mg/kg lowered the blood pressure. In the isolated rabbit heart whose accelerator nerves were intact, the perfusion with concentrations of 0.6 mug/min Hoe 933 (total dose 6 mug) decreased the release of norepinephrine from the nerve endings, reduced the positive inotropic effect, and diminished the increase in heart rate produced by electrical stimulation of the accelerator nerve. The effect of the stimulation of the accelerator nerve on dp/dt in dogs in situ was considerably diminished by such low doses as 10 and 25 mug/kg i.v. Consequently, the alkaloid inhibits sympathetic impulse transmission. Sympathetic circulatory reflexes are weakened by the compound. The alkaloid has also a ganglionic blocking effect, which is demonstrated on the upper cervical ganglion of the cat. The effect of preganglionic stimulation of the nictitating membrane was reduced with 200 mug Hoe 933/kg i.v. In the isolated guinea pig heart the effect of nicotine on heart rate and contraction was diminished. In this respect the ganglion blocker pentolinium is 8 times more active. The antifibrillatory effect of Hoe 933 was demonstrated with 0.3 mg/kg i.v. in supercooled cats, the antiarrhythmic activity was evident with 0.5 mg/kg i.v. in dogs intoxicated with K-strophanthin. In isolated hearts of guinea pigs, a dose of only 6 mug/heart inhibited ventricular fibrillation induced by aconitine and digitoxin. Even the toxicity of digoxin was diminished by previous administration of 300 mug/kg i.v. The relative refractory period and the duration of the action potential were prolonged in the isolated papillary muscle of the guinea pig heart.", "contents": "Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana. The alkaloid 13-hydroxylupanine-2-pyrrolcarbonic acid ester (Hoe 933) from the Madagascan plant Cadia ellisiana has an hypotensive and antiarrhythmic effect. The hypotensive effect in dogs, monkeys, and rats anaesthetized with barbiturates reaches its maximum with 0.2 mg/kg i.v. However, the hypotensive effect is much weaker in conscious animals. The enteral absorption in the dog is good; an intraduodenal dose of only 0.5 mg/kg lowered the blood pressure. In the isolated rabbit heart whose accelerator nerves were intact, the perfusion with concentrations of 0.6 mug/min Hoe 933 (total dose 6 mug) decreased the release of norepinephrine from the nerve endings, reduced the positive inotropic effect, and diminished the increase in heart rate produced by electrical stimulation of the accelerator nerve. The effect of the stimulation of the accelerator nerve on dp/dt in dogs in situ was considerably diminished by such low doses as 10 and 25 mug/kg i.v. Consequently, the alkaloid inhibits sympathetic impulse transmission. Sympathetic circulatory reflexes are weakened by the compound. The alkaloid has also a ganglionic blocking effect, which is demonstrated on the upper cervical ganglion of the cat. The effect of preganglionic stimulation of the nictitating membrane was reduced with 200 mug Hoe 933/kg i.v. In the isolated guinea pig heart the effect of nicotine on heart rate and contraction was diminished. In this respect the ganglion blocker pentolinium is 8 times more active. The antifibrillatory effect of Hoe 933 was demonstrated with 0.3 mg/kg i.v. in supercooled cats, the antiarrhythmic activity was evident with 0.5 mg/kg i.v. in dogs intoxicated with K-strophanthin. In isolated hearts of guinea pigs, a dose of only 6 mug/heart inhibited ventricular fibrillation induced by aconitine and digitoxin. Even the toxicity of digoxin was diminished by previous administration of 300 mug/kg i.v. The relative refractory period and the duration of the action potential were prolonged in the isolated papillary muscle of the guinea pig heart."}
{"id": "PMID:11809", "title": "The action of psychotropic drugs on DOPA induced behavioural responses in mice.", "content": "The \"DOPA potentiation\" test in mice was investigated for its usefulness in the detection of compounds with antidepressant properties. It was found that the anti-depressant drugs imipramine, amitriptyline, 5-methylamino-acetyl-6-methyl-5,6-dihydro-phenanthridine-HCl (Org OI77) and 1,2,3,4,10,14b-hexahydro-2-methyl-dibenzo[c,f]pyrazino[1,2-a]azepine-HCl (mianserin, Org GB 94) potentiated the behavioural effect of DOPA in groups of mice which had been treated 17 h previously with the monoamine oxidase inhibitor (MAOI) iproniazid. However, the DOPA response was also potentiated by a variety of centrally acting drugs which do not have antidepressant properties (atropine, methysergide, chlordiazepoxide, apomorphine). The peptide hormones ACTH4-10 and desglycinamide lysine vasopressin had equivocal effects while melanocyte stimulating hormone release-inhibiting factor (MIF) had no effect on the DOPA response. The DOPA response was inhibited by the neuroleptics chlorpromazine and haloperidol. There appeared to be no correlation between the effects of the drugs on the behavioural responses elicited by DOPA and the changes found in the brain concentration of noradrenaline, dopamine, serotonin, gamma-aminobutyric acid, tryptophan and tyrosine. It is concluded that the \"DOPA potentiation\" test cannot be considered as a reliable test in the detection of anti-depressant compounds.", "contents": "The action of psychotropic drugs on DOPA induced behavioural responses in mice. The \"DOPA potentiation\" test in mice was investigated for its usefulness in the detection of compounds with antidepressant properties. It was found that the anti-depressant drugs imipramine, amitriptyline, 5-methylamino-acetyl-6-methyl-5,6-dihydro-phenanthridine-HCl (Org OI77) and 1,2,3,4,10,14b-hexahydro-2-methyl-dibenzo[c,f]pyrazino[1,2-a]azepine-HCl (mianserin, Org GB 94) potentiated the behavioural effect of DOPA in groups of mice which had been treated 17 h previously with the monoamine oxidase inhibitor (MAOI) iproniazid. However, the DOPA response was also potentiated by a variety of centrally acting drugs which do not have antidepressant properties (atropine, methysergide, chlordiazepoxide, apomorphine). The peptide hormones ACTH4-10 and desglycinamide lysine vasopressin had equivocal effects while melanocyte stimulating hormone release-inhibiting factor (MIF) had no effect on the DOPA response. The DOPA response was inhibited by the neuroleptics chlorpromazine and haloperidol. There appeared to be no correlation between the effects of the drugs on the behavioural responses elicited by DOPA and the changes found in the brain concentration of noradrenaline, dopamine, serotonin, gamma-aminobutyric acid, tryptophan and tyrosine. It is concluded that the \"DOPA potentiation\" test cannot be considered as a reliable test in the detection of anti-depressant compounds."}
{"id": "PMID:11810", "title": "Investigation of phosphatidylethanolamine bilayers by deuterium and phosphorus-31 nuclear magnetic resonance.", "content": "The motion of the ethanolamine head group in unsonicated lipid bilayers above and below the phase transition is studied by means of deuterium and phosphorus magnetic resonance. For this purpose, dipalmitoyl-3-sn-phosphatidylethanolamine is selectively deuterated at the two ethanolamine carbon atoms. The deuterium quadrupole splittings of the corresponding bilayer phases are measured at pH 5.5 as a function of temperature. In addition, the phosphorus-31 chemical shift anisotropies of planor-oriented and randomly dispersed samples of dipalmitoyl-3-sn-phosphatidylethanolamine are measured at pH 5.5 and 11 by applying a proton-decoupling field. The knowledge of the static chemical shift tensor (Kohler, S.J., and Klein, M.P. (1976), Biochemistry 15, 967) provides the basis for a quantitive analysis of the head-group motion. The nuclear magnetic resonance data are consistent with a model in which the ethanolamine group is rotating flat on the surface of the bilayer with rapid transitions occurring between two enantiomeric conformations.", "contents": "Investigation of phosphatidylethanolamine bilayers by deuterium and phosphorus-31 nuclear magnetic resonance. The motion of the ethanolamine head group in unsonicated lipid bilayers above and below the phase transition is studied by means of deuterium and phosphorus magnetic resonance. For this purpose, dipalmitoyl-3-sn-phosphatidylethanolamine is selectively deuterated at the two ethanolamine carbon atoms. The deuterium quadrupole splittings of the corresponding bilayer phases are measured at pH 5.5 as a function of temperature. In addition, the phosphorus-31 chemical shift anisotropies of planor-oriented and randomly dispersed samples of dipalmitoyl-3-sn-phosphatidylethanolamine are measured at pH 5.5 and 11 by applying a proton-decoupling field. The knowledge of the static chemical shift tensor (Kohler, S.J., and Klein, M.P. (1976), Biochemistry 15, 967) provides the basis for a quantitive analysis of the head-group motion. The nuclear magnetic resonance data are consistent with a model in which the ethanolamine group is rotating flat on the surface of the bilayer with rapid transitions occurring between two enantiomeric conformations."}
{"id": "PMID:11811", "title": "Fluorine-containing analogues of intermediates in the Shikimate pathway.", "content": "The phosphoenolpyruvate analogue (Z)-phosphoenol-3-fluoropyruvate is a substrate for phenylalanine-inhibitable 3-deoxy-D-arabino-heptulosonic acid-7-phosphate synthase from Escherichia coli. In the presence of excess erythrose 4-phosphate, apparent KM values of 65 and 38 muM were observed for phosphoenol-3-fluoropyruvate and phosphoenolpyruvate, respectively. Because the apparent Vmax for phosphoenol-3-fluoropyruvate is only 1.17% of that for phosphoenolpyruvate, one can study the former as an inhibitor of 3-deoxy-arabino-heptulosonic acid-7-phosphate synthase. Kinetic experiments showed phosphoenol-3-fluoropyruvate to be competitive with respect to phosphoenolpyruvate. Two distinguishable Ki values of 8 and 48 muM were obtained. The product (3S)-3-deoxy--3-fluoro-arabino-heptulosonic acid 7-phosphate was purified, characterized, and shown to act as a substrate for 5-dehydroquinate synthase. 3-Deoxy-3-fluoro-arabino-heptulosonic acid 7-phosphate, in contrast to 3-deoxy-arabino-heptulosonic acid 7-phosphate reacts slowly or not at all with reagents specific for 2-keto-3-deoxy sugars and is relatively resistant to oxidative cleavage by sodium periodate. The expected product of periodate oxidation, 3-fluoro-3-formylpyruvate, cannot be detected. This observation was clarified by studies with model compounds.", "contents": "Fluorine-containing analogues of intermediates in the Shikimate pathway. The phosphoenolpyruvate analogue (Z)-phosphoenol-3-fluoropyruvate is a substrate for phenylalanine-inhibitable 3-deoxy-D-arabino-heptulosonic acid-7-phosphate synthase from Escherichia coli. In the presence of excess erythrose 4-phosphate, apparent KM values of 65 and 38 muM were observed for phosphoenol-3-fluoropyruvate and phosphoenolpyruvate, respectively. Because the apparent Vmax for phosphoenol-3-fluoropyruvate is only 1.17% of that for phosphoenolpyruvate, one can study the former as an inhibitor of 3-deoxy-arabino-heptulosonic acid-7-phosphate synthase. Kinetic experiments showed phosphoenol-3-fluoropyruvate to be competitive with respect to phosphoenolpyruvate. Two distinguishable Ki values of 8 and 48 muM were obtained. The product (3S)-3-deoxy--3-fluoro-arabino-heptulosonic acid 7-phosphate was purified, characterized, and shown to act as a substrate for 5-dehydroquinate synthase. 3-Deoxy-3-fluoro-arabino-heptulosonic acid 7-phosphate, in contrast to 3-deoxy-arabino-heptulosonic acid 7-phosphate reacts slowly or not at all with reagents specific for 2-keto-3-deoxy sugars and is relatively resistant to oxidative cleavage by sodium periodate. The expected product of periodate oxidation, 3-fluoro-3-formylpyruvate, cannot be detected. This observation was clarified by studies with model compounds."}
{"id": "PMID:11812", "title": "Characterization of the recombination reaction of rhodopsin.", "content": "The kinetics of recombination of 11-cis-retinal with bleached rod outer segments and sodium cholate solubilized rhodopsin have been investigated. At neutral pH, it was found that bleached rod outer segments in the presence of an excess of 11-cis-retinal follow pseudo-first-order kinetics. The results suggest the second-order formation of an intermediate addition compound followed by a first-order dehydration step to form a protonated aldimine linkage. In addition, at pH values above 7.5 or below 6.5 the kinetics of recombination are complex, indicating the formation of a molecular species inactive in recombination which is in equilibrium with the active form of opsin. Based upon the observed rate constants as a function of pH, a scheme is presented to describe the recombination reaction in bleached rod outer segments. The kinetics of recombination of sodium cholate solubilized opsin were also analyzed. In terms of formation of an intermediate addition compound and subsequent dehydration, the values for the individual rate constants for both bleached rod outer segments and cholate-solubilized opsin were found to compare very favorably. These results demonstrate that the sodium cholate (2 mg/ml) maintains opsin in a conformation very similar to that in the rod outer segment membrane and suggest that the cholate-opsin complex is an excellent model system for studies on opsin-membrane interactions.", "contents": "Characterization of the recombination reaction of rhodopsin. The kinetics of recombination of 11-cis-retinal with bleached rod outer segments and sodium cholate solubilized rhodopsin have been investigated. At neutral pH, it was found that bleached rod outer segments in the presence of an excess of 11-cis-retinal follow pseudo-first-order kinetics. The results suggest the second-order formation of an intermediate addition compound followed by a first-order dehydration step to form a protonated aldimine linkage. In addition, at pH values above 7.5 or below 6.5 the kinetics of recombination are complex, indicating the formation of a molecular species inactive in recombination which is in equilibrium with the active form of opsin. Based upon the observed rate constants as a function of pH, a scheme is presented to describe the recombination reaction in bleached rod outer segments. The kinetics of recombination of sodium cholate solubilized opsin were also analyzed. In terms of formation of an intermediate addition compound and subsequent dehydration, the values for the individual rate constants for both bleached rod outer segments and cholate-solubilized opsin were found to compare very favorably. These results demonstrate that the sodium cholate (2 mg/ml) maintains opsin in a conformation very similar to that in the rod outer segment membrane and suggest that the cholate-opsin complex is an excellent model system for studies on opsin-membrane interactions."}
{"id": "PMID:11815", "title": "Energy tranduction in photosynthetic bacteria. XI. Further resolution of cytochromes of b type and the nature of the co-sensitive oxidase present in the respiratory chain of Rhodopseudomonas capsulata.", "content": "1. In membranes prepared from dark grown cells of Rhodopseudomonas capsulata, five cytochromes of b type (E'0 at pH 7.0 +413+/-5, +270+/-5, +148+/-5, +56+/-5 and -32+/-5 mV) can be detected by redox titrations at different pH values. The midpoint potentials of only three of these cytochromes (b148, b56, and b-32) vary as a function of pH with a slope of 30 mV per pH unit. 2. In the presence of a CO/N2 mixture, the apparent E'0 of cytochrome b270 shifts markedly towards higher potentials (+355mV); a similar but less pronounced shift is apparent also for cytochrome b150. The effect of CO on the midpoint potential of cytochrome b270 is absent in the respiration deficient mutant M6 which possesses a specific lesion in the CO-sensitive segment of the branched respiratory chain present in the wild type strain. 3. Preparations of spheroplasts with lysozyme digestion lead to the release of a large amount of cytochrome c2 and of virtually all cytochrome cc'. These preparations show a respiratory chain impaired in the electron pathway sensitive to low KCN concentration, in agreement with the proposed role of cytochrome c2 in this branch; on the contrary, the activity of the CO-sensitive branch remains unaffected, indicating that neither cytochrome c2 nor the CO-binding cytochrome cc' are involved in this pathway. 4. Membranes prepared from spheroplasts still possess a CO-binding pigment characterized by maxima at 420.5, 543 and 574 nm and minima at 431, 560 nm in C0-difference spectra and with an alpha band at 562.5 nm in reduced minus oxidized difference spectra. This membrane-bound cytochrome, which is coincident with cytochrome b270, can be classified as a typical cytochrome \"0\" and considered the alternative CO-sensitive oxidase.", "contents": "Energy tranduction in photosynthetic bacteria. XI. Further resolution of cytochromes of b type and the nature of the co-sensitive oxidase present in the respiratory chain of Rhodopseudomonas capsulata. 1. In membranes prepared from dark grown cells of Rhodopseudomonas capsulata, five cytochromes of b type (E'0 at pH 7.0 +413+/-5, +270+/-5, +148+/-5, +56+/-5 and -32+/-5 mV) can be detected by redox titrations at different pH values. The midpoint potentials of only three of these cytochromes (b148, b56, and b-32) vary as a function of pH with a slope of 30 mV per pH unit. 2. In the presence of a CO/N2 mixture, the apparent E'0 of cytochrome b270 shifts markedly towards higher potentials (+355mV); a similar but less pronounced shift is apparent also for cytochrome b150. The effect of CO on the midpoint potential of cytochrome b270 is absent in the respiration deficient mutant M6 which possesses a specific lesion in the CO-sensitive segment of the branched respiratory chain present in the wild type strain. 3. Preparations of spheroplasts with lysozyme digestion lead to the release of a large amount of cytochrome c2 and of virtually all cytochrome cc'. These preparations show a respiratory chain impaired in the electron pathway sensitive to low KCN concentration, in agreement with the proposed role of cytochrome c2 in this branch; on the contrary, the activity of the CO-sensitive branch remains unaffected, indicating that neither cytochrome c2 nor the CO-binding cytochrome cc' are involved in this pathway. 4. Membranes prepared from spheroplasts still possess a CO-binding pigment characterized by maxima at 420.5, 543 and 574 nm and minima at 431, 560 nm in C0-difference spectra and with an alpha band at 562.5 nm in reduced minus oxidized difference spectra. This membrane-bound cytochrome, which is coincident with cytochrome b270, can be classified as a typical cytochrome \"0\" and considered the alternative CO-sensitive oxidase."}
{"id": "PMID:11816", "title": "Light-dependent changes of the Mg2+ concentration in the stroma in relation to the Mg2+ dependency of CO2 fixation in intact chloroplasts.", "content": "(1) Light-dependent changes of the Mg2+ content of thylakoid membranes were measured at pH 8.0 and compared with earlier measurements at pH 6.6. In a NaCl and KCl medium, the light-dependent decrease in the Mg2+ content of the thylakoid membranes at pH 8.0 is found to be 23 nmol Mg2+ per mg chlorophyll, whereas in a sorbitol medium it is 83 nmol Mg2+ per mg chlorophyll. (2) A light dependent increase in the Mg2+ content of the stroma was detected wjem chloroplasts were subjected to osmotic shock, amounting to 26 nmol/mg chlorophyll. Furthermore, a rapid and reversible light-dependent efflux of Mg2+ has been observed in intact chloroplasts when the divalent cation ionophore A 23 187 was added, indicating a light-dependent transfer of about 60 nmol of Mg2+ per mg chlorophyll from the thylakoid membranes to the stroma. (3) CO2 fixation, but not phosphoglycerate reduction, could be completely inhibited when A 23 187 was added to intact chloroplasts in the absence of external Mg2+. If Mg2+ was then added to the medium, CO2 fixation was restored. Half of the maximal restoration was achieved with about 0.2 mM Mg2+, which is calculated to reflect a Mg2+ concentration in the stroma of 1.2 mM. The further addition of Ca2+ strongly inhibits CO2 fixation. (4) The results suggest that illumination of intact chloroplasts causes an increase in the Mg2+ concentration of 1-3 mM in the stroma. Compared to the total Mg2+ content of chloroplasts, this increase is very low, but it appears to be high enough to have a possible function in the light regulation of CO2 fixation.", "contents": "Light-dependent changes of the Mg2+ concentration in the stroma in relation to the Mg2+ dependency of CO2 fixation in intact chloroplasts. (1) Light-dependent changes of the Mg2+ content of thylakoid membranes were measured at pH 8.0 and compared with earlier measurements at pH 6.6. In a NaCl and KCl medium, the light-dependent decrease in the Mg2+ content of the thylakoid membranes at pH 8.0 is found to be 23 nmol Mg2+ per mg chlorophyll, whereas in a sorbitol medium it is 83 nmol Mg2+ per mg chlorophyll. (2) A light dependent increase in the Mg2+ content of the stroma was detected wjem chloroplasts were subjected to osmotic shock, amounting to 26 nmol/mg chlorophyll. Furthermore, a rapid and reversible light-dependent efflux of Mg2+ has been observed in intact chloroplasts when the divalent cation ionophore A 23 187 was added, indicating a light-dependent transfer of about 60 nmol of Mg2+ per mg chlorophyll from the thylakoid membranes to the stroma. (3) CO2 fixation, but not phosphoglycerate reduction, could be completely inhibited when A 23 187 was added to intact chloroplasts in the absence of external Mg2+. If Mg2+ was then added to the medium, CO2 fixation was restored. Half of the maximal restoration was achieved with about 0.2 mM Mg2+, which is calculated to reflect a Mg2+ concentration in the stroma of 1.2 mM. The further addition of Ca2+ strongly inhibits CO2 fixation. (4) The results suggest that illumination of intact chloroplasts causes an increase in the Mg2+ concentration of 1-3 mM in the stroma. Compared to the total Mg2+ content of chloroplasts, this increase is very low, but it appears to be high enough to have a possible function in the light regulation of CO2 fixation."}
{"id": "PMID:11817", "title": "Studies on the ferrochelatase activity of isolated rat liver mitochondria with special reference to the effect of oxidizable substrates and oxygen concentration.", "content": "The mitochondrial ferrochelatase activity has been studied in coupled rat liver mitochondria using deuteroporphyrin IX (incorporated into liposomes of lecithin) and Fe(III) or Co(II) as the substrates. 1. It was found that respiring mitochondria catalyze the insertion of Fe(II) and Co(II) into deuteroporphyrin. When Fe(III) was used as the metal donor, the reaction revealed an absolute requirement for a supply of reducing equivalents supported by the respiratory chain. 2. A close correlation was found between the disappearance of porphyrin and the formation of heme which allows an accurate estimate of the extinction coefficient for the porphyrin to heme conversion. The value deltae (mM-1 - cm-1) = 3.5 for the wavelength pair 498 509 nm, is considerably lower than previously reported. 3. The maximal rate of deuteroheme synthesis was found to be approx. 1 nM - min-1 - mg-1 of protein at 37 degrees C, PH 7.4 and optimal substrate concentrations, i.e. 75 muM Fe(III) and 50 muM deuteroporphyrin. 4. Provided the mitochondria are supplemented with an oxidizable substrate, the presence of oxygen has no effect on the rate of deuteroheme synthesis.", "contents": "Studies on the ferrochelatase activity of isolated rat liver mitochondria with special reference to the effect of oxidizable substrates and oxygen concentration. The mitochondrial ferrochelatase activity has been studied in coupled rat liver mitochondria using deuteroporphyrin IX (incorporated into liposomes of lecithin) and Fe(III) or Co(II) as the substrates. 1. It was found that respiring mitochondria catalyze the insertion of Fe(II) and Co(II) into deuteroporphyrin. When Fe(III) was used as the metal donor, the reaction revealed an absolute requirement for a supply of reducing equivalents supported by the respiratory chain. 2. A close correlation was found between the disappearance of porphyrin and the formation of heme which allows an accurate estimate of the extinction coefficient for the porphyrin to heme conversion. The value deltae (mM-1 - cm-1) = 3.5 for the wavelength pair 498 509 nm, is considerably lower than previously reported. 3. The maximal rate of deuteroheme synthesis was found to be approx. 1 nM - min-1 - mg-1 of protein at 37 degrees C, PH 7.4 and optimal substrate concentrations, i.e. 75 muM Fe(III) and 50 muM deuteroporphyrin. 4. Provided the mitochondria are supplemented with an oxidizable substrate, the presence of oxygen has no effect on the rate of deuteroheme synthesis."}
{"id": "PMID:11818", "title": "Photoinactivation of photophosphorylation and dark ATPase in Rhodospirillum rubrum chromatophores.", "content": "Preillumination of Rhodospirillum rubrum chromatophores with strong, far-red light in the presence of phenazine methosulfate under non-phosphorylation conditions results in a selective, irreversible inactivation (typically about 70%) of photophosphorylation and of uncoupler-stimulated dark ATPase. The time course of the photoinactivation is similar to the light-on kinetics of the light-induced proton uptake in the absence of ADP. Only little photoinactivation occurs when the uncoupler carbonyl cyanide m-chlorophenyl hydrazone is present or when phenazine methosulfate is absent during the preillumination, indicating that the reaction occurs only when the membrane is energized. Phosphorylation conditions offer a practically complete protection against the photoinactivation. Inorganic phosphate, Mg2+ or ADP do not provide a significant protection against the photoinactivation, nor does ATP. The pH-dependence of the reaction(s) leading to photoinactivation may indicate that a partial reaction of the photophosphorylation process (perhaps only a conformational change of the coupling factor) precedes the photoinactivation.", "contents": "Photoinactivation of photophosphorylation and dark ATPase in Rhodospirillum rubrum chromatophores. Preillumination of Rhodospirillum rubrum chromatophores with strong, far-red light in the presence of phenazine methosulfate under non-phosphorylation conditions results in a selective, irreversible inactivation (typically about 70%) of photophosphorylation and of uncoupler-stimulated dark ATPase. The time course of the photoinactivation is similar to the light-on kinetics of the light-induced proton uptake in the absence of ADP. Only little photoinactivation occurs when the uncoupler carbonyl cyanide m-chlorophenyl hydrazone is present or when phenazine methosulfate is absent during the preillumination, indicating that the reaction occurs only when the membrane is energized. Phosphorylation conditions offer a practically complete protection against the photoinactivation. Inorganic phosphate, Mg2+ or ADP do not provide a significant protection against the photoinactivation, nor does ATP. The pH-dependence of the reaction(s) leading to photoinactivation may indicate that a partial reaction of the photophosphorylation process (perhaps only a conformational change of the coupling factor) precedes the photoinactivation."}
{"id": "PMID:11819", "title": "Control of synbiotic nitrogen fixation in Rhizobia. Regulation of NH4+ assimilation.", "content": "This communication is concerned with physiological, biochemical, and genetic studies of the regulation of ammonium (NH4+) assimilation by Rhizobia (root nodule bacteria) that infect leguminous plants. The major conclutions are (i) physiological studies show that Rhizobia are able to assimilate NH4+ for growth only when supplemented with certain organic nitrogen sources (e.g., L-aspartate, L-leucine, L-serine). Addition of as little as 2 mug/ml of L-aspartate supported growth on NH4+ as nitrogen source. In contrast, addition of glutamate in combination with NH4+-blocked NH4+ utilization; (ii) biochemical analysis show that glutamate synthase activity (NADP- and NAD-linked) is always present in cells capable of assimilating NH4+; also cells without glutamate synthase activity were found to be incapable of NH4+ utilization. Glutamate synthase levels were observed to fluctuate markedly depending on the available nitrogen source and on the growth stage of the culture; (iii) mutants were selected in which assimilation of NH4+ is no longer subject to inhibition (repression?) by glutamate. The levels of glutamate synthase activity (NADP-linked) (in the presence of glutamate) show approximately a two-fold increase over the level in the parent strain. The mutants no longer require supplementation with small amounts of organic nitrogen for growth in medium containing inorganic nitrogen (e.g., NH4+ or NO3-); (iv) these findings are discussed in relation to the working model of symbiotic nitrogen fixation recently proposed (O'Gara and Shanmugam (1976), Biochim. Biophys. Acta 437, 313--321).", "contents": "Control of synbiotic nitrogen fixation in Rhizobia. Regulation of NH4+ assimilation. This communication is concerned with physiological, biochemical, and genetic studies of the regulation of ammonium (NH4+) assimilation by Rhizobia (root nodule bacteria) that infect leguminous plants. The major conclutions are (i) physiological studies show that Rhizobia are able to assimilate NH4+ for growth only when supplemented with certain organic nitrogen sources (e.g., L-aspartate, L-leucine, L-serine). Addition of as little as 2 mug/ml of L-aspartate supported growth on NH4+ as nitrogen source. In contrast, addition of glutamate in combination with NH4+-blocked NH4+ utilization; (ii) biochemical analysis show that glutamate synthase activity (NADP- and NAD-linked) is always present in cells capable of assimilating NH4+; also cells without glutamate synthase activity were found to be incapable of NH4+ utilization. Glutamate synthase levels were observed to fluctuate markedly depending on the available nitrogen source and on the growth stage of the culture; (iii) mutants were selected in which assimilation of NH4+ is no longer subject to inhibition (repression?) by glutamate. The levels of glutamate synthase activity (NADP-linked) (in the presence of glutamate) show approximately a two-fold increase over the level in the parent strain. The mutants no longer require supplementation with small amounts of organic nitrogen for growth in medium containing inorganic nitrogen (e.g., NH4+ or NO3-); (iv) these findings are discussed in relation to the working model of symbiotic nitrogen fixation recently proposed (O'Gara and Shanmugam (1976), Biochim. Biophys. Acta 437, 313--321)."}
{"id": "PMID:11821", "title": "Conformational dependence on pH in tripeptides.", "content": "From the 1H-NMR study of Tyr-Gly-Gly and Phe-Gly-Gly in H2O and 2H2O as a function of pH it follows that these tripeptides display at least two and probably three conformational zones. Under slow exchange conditions of the peptidic NH-protons, coupling constants 3J(NH, CaH) may be extracted as the probe. At higher pH values shift values and 3J(a, beta) of the side chain and the titration curves are indicative for these conformational alterations.", "contents": "Conformational dependence on pH in tripeptides. From the 1H-NMR study of Tyr-Gly-Gly and Phe-Gly-Gly in H2O and 2H2O as a function of pH it follows that these tripeptides display at least two and probably three conformational zones. Under slow exchange conditions of the peptidic NH-protons, coupling constants 3J(NH, CaH) may be extracted as the probe. At higher pH values shift values and 3J(a, beta) of the side chain and the titration curves are indicative for these conformational alterations."}
{"id": "PMID:11822", "title": "Inactivation of Streptomyces subtilisin inhibitory by chemical modifications.", "content": "1. The inhibitory activity of an alkaline protease inhibitor, (Streptomyces subtilisin inhibitor) towards subtilisin is found to decrease by photooxidation sensitized by methylene blue with a clear pH dependence, the midpoint of which is about 6.0. 2. Amino acid analyses of photooxidized Streptomyces subtilisin inhibitor indicate that one of the two histidyl residues and the three methionyl residues are destroyed, concomittant with the loss of inhibitory activity. 3. In accordance with this observation, one of the clearly resolved nuclear magnetic resonances from C2-protons of the two histidyl residues is selectively diminished. This histidyl residue, sensitive to photooxidation and giving a proton magnetic resonance peak at lower field, is assigned to His-106 from peptide analyses. 4. Independent modification of methionyl residues by a reaction with H2O2 or Cl2 also decreases the inhibitory activity of Streptomyces subtilisin inhibitor. 5. Modification of lysyl, tyrosyl and tryptophanyl residues by diazonium-1-H-tetrazole does not lead to the loss of the inhibitory activity. 6. The above results indicate that one or more methionyl residue(s) are essential to the inhibitory activity of Streptomyces subtilisin inhibitor, whereas lysyl, tyrosyl and tryptophanyl residues are not essential to the inhibitory activity. Modification of His-106 is also strongly related to the loss of activity, although its distinct participation in the inactivation mechanism has not been demonstrated.", "contents": "Inactivation of Streptomyces subtilisin inhibitory by chemical modifications. 1. The inhibitory activity of an alkaline protease inhibitor, (Streptomyces subtilisin inhibitor) towards subtilisin is found to decrease by photooxidation sensitized by methylene blue with a clear pH dependence, the midpoint of which is about 6.0. 2. Amino acid analyses of photooxidized Streptomyces subtilisin inhibitor indicate that one of the two histidyl residues and the three methionyl residues are destroyed, concomittant with the loss of inhibitory activity. 3. In accordance with this observation, one of the clearly resolved nuclear magnetic resonances from C2-protons of the two histidyl residues is selectively diminished. This histidyl residue, sensitive to photooxidation and giving a proton magnetic resonance peak at lower field, is assigned to His-106 from peptide analyses. 4. Independent modification of methionyl residues by a reaction with H2O2 or Cl2 also decreases the inhibitory activity of Streptomyces subtilisin inhibitor. 5. Modification of lysyl, tyrosyl and tryptophanyl residues by diazonium-1-H-tetrazole does not lead to the loss of the inhibitory activity. 6. The above results indicate that one or more methionyl residue(s) are essential to the inhibitory activity of Streptomyces subtilisin inhibitor, whereas lysyl, tyrosyl and tryptophanyl residues are not essential to the inhibitory activity. Modification of His-106 is also strongly related to the loss of activity, although its distinct participation in the inactivation mechanism has not been demonstrated."}
{"id": "PMID:11823", "title": "Use of an iridium electrode for direct measurements of pI of proteins after isoelectric focusing in polyacrylamide gel.", "content": "The use of an iridium microelectrode 0.5 mm in diameter is proposed for measuring the pH gradient in polyacrylamide gels after isoelectric focusing. The electrode exhibits a perfectly linear potential/pH relationship; thus it can be used directly in conjunction with a pH meter using the pH scale for readings. pH equilibrium values are rapidly reached (10-15 s) and pI determinations are obtainable with good accuracy (better than 0.1 pH).", "contents": "Use of an iridium electrode for direct measurements of pI of proteins after isoelectric focusing in polyacrylamide gel. The use of an iridium microelectrode 0.5 mm in diameter is proposed for measuring the pH gradient in polyacrylamide gels after isoelectric focusing. The electrode exhibits a perfectly linear potential/pH relationship; thus it can be used directly in conjunction with a pH meter using the pH scale for readings. pH equilibrium values are rapidly reached (10-15 s) and pI determinations are obtainable with good accuracy (better than 0.1 pH)."}
{"id": "PMID:11824", "title": "Fluorescence properties of 2' (or 3')-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate and its use in the study of binding to heavy meromyosin ATPase.", "content": "2' (or 3')-O-(2,4,6-Trinitrophenyl) adenosine 5'-triphosphate (N3ph-ATP), which contains a Meisenheimer complex moiety, is one of the class of compounds which do not fluoresce in water but fluoresce both in low polarity solvents and when bound to the protein molecule. Fluorescence intensity of N3ph-ATP in the range of 540 nm, when excited at 410 nm, decreased with increasing the solvent polarity accompanying the increment of the wavelength of maximum emission. When bound to heavy meromyosin ATPase, the fluorescence properties of N3ph-ADP were almost the same as those of N3ph-ATP in a low polarity solvent, suggesting that N3ph-ADP was bound to hydrophobic area on heavy meromyosin ATPase.", "contents": "Fluorescence properties of 2' (or 3')-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate and its use in the study of binding to heavy meromyosin ATPase. 2' (or 3')-O-(2,4,6-Trinitrophenyl) adenosine 5'-triphosphate (N3ph-ATP), which contains a Meisenheimer complex moiety, is one of the class of compounds which do not fluoresce in water but fluoresce both in low polarity solvents and when bound to the protein molecule. Fluorescence intensity of N3ph-ATP in the range of 540 nm, when excited at 410 nm, decreased with increasing the solvent polarity accompanying the increment of the wavelength of maximum emission. When bound to heavy meromyosin ATPase, the fluorescence properties of N3ph-ADP were almost the same as those of N3ph-ATP in a low polarity solvent, suggesting that N3ph-ADP was bound to hydrophobic area on heavy meromyosin ATPase."}
{"id": "PMID:11825", "title": "Purification and characterization of a coagulant protein from the venom of Russell's viper.", "content": "The coagulant protein from the venom of Russell's viper was purified by means of successive chromatography on Sephadex G-50, DEAE-cellulose and Sephadex G-200. The purified coagulant protein was homogeneous by polyacrylamide gel electrophoresis and ultracentrifugation. The molecular weight was estimated to be about 100 000 by ultracentrifuge analysis and 130 000 by gel filtration. The coagulant protein contains 11.1% carbohydrate which includes 5.1% hexose (galactose: mannose = 1:1), 5% hexosamine (glucosamine), and 1% neuraminic acid (N-acetylneuraminic  acid and N-glycolyneuraminic acid). The isoelectric point is pH 6.3. The results of both sodium dodecyl sulfate electrophoresis and gel filtration in 6 M guanidium chloride suggest that it consists of four polypeptide chains. The coagulant protein functions as an enzyme in activating blood coagulation factor X in the presence of Ca2+. N-a-p-Toluenesulfonyl-L-arginine methyl ester hydrolyzing activity in the preparation definitely decreased during purification and it suggests that the clotting activity is not associated with the esterase activity. The clotting activity is inhibited by diisopropyl phosphorofluoridate and by phenylmethylsulfonyl fluoride, suggesting that the coagulant protein is a serine protease. The optimum pH is between pH 7.0 and pH 8.0. At neutral pH the coagulant protein is stable below 50 degrees C, but is rapidly inactivated above 55 degrees C.", "contents": "Purification and characterization of a coagulant protein from the venom of Russell's viper. The coagulant protein from the venom of Russell's viper was purified by means of successive chromatography on Sephadex G-50, DEAE-cellulose and Sephadex G-200. The purified coagulant protein was homogeneous by polyacrylamide gel electrophoresis and ultracentrifugation. The molecular weight was estimated to be about 100 000 by ultracentrifuge analysis and 130 000 by gel filtration. The coagulant protein contains 11.1% carbohydrate which includes 5.1% hexose (galactose: mannose = 1:1), 5% hexosamine (glucosamine), and 1% neuraminic acid (N-acetylneuraminic  acid and N-glycolyneuraminic acid). The isoelectric point is pH 6.3. The results of both sodium dodecyl sulfate electrophoresis and gel filtration in 6 M guanidium chloride suggest that it consists of four polypeptide chains. The coagulant protein functions as an enzyme in activating blood coagulation factor X in the presence of Ca2+. N-a-p-Toluenesulfonyl-L-arginine methyl ester hydrolyzing activity in the preparation definitely decreased during purification and it suggests that the clotting activity is not associated with the esterase activity. The clotting activity is inhibited by diisopropyl phosphorofluoridate and by phenylmethylsulfonyl fluoride, suggesting that the coagulant protein is a serine protease. The optimum pH is between pH 7.0 and pH 8.0. At neutral pH the coagulant protein is stable below 50 degrees C, but is rapidly inactivated above 55 degrees C."}
{"id": "PMID:11826", "title": "Competitive binding of iron by transferrins from different vertebrates.", "content": "1. A competitive dialysis technique has been used to study the relative affinities of the two iron-binding sites on transferrin molecules and the relative binding strengths of transferrins isolated from plasma of different species. 2. The comparisons were extended to include desialylated human transferrin, ovotransferrin, and a cyanogen bromide fragment of the latter. 3. Although the results of bilateral experiments could generally be accounted for in terms of the theory of independent sites, there were some exceptions, and cyclic comparisons were inconsistent. 4. All the comparisons made were compatible with a model in which site-interaction occurred, but it was not possible to decide whether the sites were intrinsically identical or not. For most species this corresponded to positive cooperativity, but for rabbit it was negative. 5. The average affinity of transferrin for iron depended on species, but the variation was never more than about one order of magnitude. 6. No effect on the binding constants for human transferrin could be detected when the sialic acid residues were removed. 7. The fragment of ovotransferrin competed fairly effectively with the native molecule for iron, although the average relative affinity was only about 1:15. 8. The relative binding of iron by ovotranferrin and human transferrin was affected little when bicarbonate anion was replaced by oxalate, although the ratio of the two binding constants for ovotranferrin increased.", "contents": "Competitive binding of iron by transferrins from different vertebrates. 1. A competitive dialysis technique has been used to study the relative affinities of the two iron-binding sites on transferrin molecules and the relative binding strengths of transferrins isolated from plasma of different species. 2. The comparisons were extended to include desialylated human transferrin, ovotransferrin, and a cyanogen bromide fragment of the latter. 3. Although the results of bilateral experiments could generally be accounted for in terms of the theory of independent sites, there were some exceptions, and cyclic comparisons were inconsistent. 4. All the comparisons made were compatible with a model in which site-interaction occurred, but it was not possible to decide whether the sites were intrinsically identical or not. For most species this corresponded to positive cooperativity, but for rabbit it was negative. 5. The average affinity of transferrin for iron depended on species, but the variation was never more than about one order of magnitude. 6. No effect on the binding constants for human transferrin could be detected when the sialic acid residues were removed. 7. The fragment of ovotransferrin competed fairly effectively with the native molecule for iron, although the average relative affinity was only about 1:15. 8. The relative binding of iron by ovotranferrin and human transferrin was affected little when bicarbonate anion was replaced by oxalate, although the ratio of the two binding constants for ovotranferrin increased."}
{"id": "PMID:11827", "title": "Effect of divalent metal ions on the digestibility of concanavalin A by endopeptidases.", "content": "Demetallized concanavalin A is degraded rapidly at pH 7.0 and 8.2 by alpha-chymotrypsin, thermolysin or trypsin, yielding peptide fragments devoid of ability to bind to Sephadex G-75. Addition of Ni2+ and of Ca2+ confers on concanavalin A high resistance towards proteolytic attack so that even after long periods of exposure to the enzymes, almost all of the saccharide-binding capacity is preserved. Ni2+ alone protects strongly at pH 7.0 but not at pH 8.2. Apparently, both the transition metal ion and Ca2+ play an important role in stabilizing the native conformation of the protein molecule. Digestion of demetallized concanavalin A with alpha-chymotrypsin or thermolysin readily yields small peptide fragments (Mr less than 10 000), while trypsin yields as the major product(s) larger peptide(s) (Mr approximately 20 000) of appreciable resistance to further fragmentation.", "contents": "Effect of divalent metal ions on the digestibility of concanavalin A by endopeptidases. Demetallized concanavalin A is degraded rapidly at pH 7.0 and 8.2 by alpha-chymotrypsin, thermolysin or trypsin, yielding peptide fragments devoid of ability to bind to Sephadex G-75. Addition of Ni2+ and of Ca2+ confers on concanavalin A high resistance towards proteolytic attack so that even after long periods of exposure to the enzymes, almost all of the saccharide-binding capacity is preserved. Ni2+ alone protects strongly at pH 7.0 but not at pH 8.2. Apparently, both the transition metal ion and Ca2+ play an important role in stabilizing the native conformation of the protein molecule. Digestion of demetallized concanavalin A with alpha-chymotrypsin or thermolysin readily yields small peptide fragments (Mr less than 10 000), while trypsin yields as the major product(s) larger peptide(s) (Mr approximately 20 000) of appreciable resistance to further fragmentation."}
{"id": "PMID:11828", "title": "Hemoglobin Fannin-Lubbock [alpha2 beta 2 119 (GH2) Gly replaced by Asp]. A new hemoglobin variant at the alpha1 beta 1 contact.", "content": "Hemoglobin Fannin-Lubbock was found in a 9-year-old Mexican-American female. The abnormal hemoglobin was detected as a fast-moving variant by electrophoresis on cellulose acetate at pH 8.4. Structural analysis indicated a substitution in the beta-chain of aspartic acid for glycine at position 119, a position involved in the alpha1beta1 contact of the hemoglobin tetramer. This contact between unlike chains is larger and undergoes a smaller shift during the process of oxygenation and deoxygenation that the alpha1beta2 contact (Perutz, M.F., Muirhead, H., Cox, J.M. and Goaman, L.C.G. (1968) Nature 219, 131-139). Mutations in this contact tend to cause slight or no changes in functional behavior. Apart from a mild anemia, the propositus did not exhibit any obvious clinical symptoms.", "contents": "Hemoglobin Fannin-Lubbock [alpha2 beta 2 119 (GH2) Gly replaced by Asp]. A new hemoglobin variant at the alpha1 beta 1 contact. Hemoglobin Fannin-Lubbock was found in a 9-year-old Mexican-American female. The abnormal hemoglobin was detected as a fast-moving variant by electrophoresis on cellulose acetate at pH 8.4. Structural analysis indicated a substitution in the beta-chain of aspartic acid for glycine at position 119, a position involved in the alpha1beta1 contact of the hemoglobin tetramer. This contact between unlike chains is larger and undergoes a smaller shift during the process of oxygenation and deoxygenation that the alpha1beta2 contact (Perutz, M.F., Muirhead, H., Cox, J.M. and Goaman, L.C.G. (1968) Nature 219, 131-139). Mutations in this contact tend to cause slight or no changes in functional behavior. Apart from a mild anemia, the propositus did not exhibit any obvious clinical symptoms."}
{"id": "PMID:11830", "title": "An unusual fluorescence spectrum of a protein proteinase inhibitor, Streptomyces subtilisin inhibitor.", "content": "Streptomyces subtilisin inhibitor, a dimeric protein proteinase inhibitor isolated in crystalline form by Murae et al. in 1972, contains three tyrosine and one tryptophan residues per monomer unit and has unusual fluorescence properties. When excited at 280 nm, it shows a characteristic fluorescence spectrum having a peak at 307 nm and a shoulder near 340 nm, a feature which has been recognized only for a very few cases in proteins containing both tryosine and tryptophan residues. When excited at 295 nm, at which tryrosine scarcely absorbs, the inhibitor shows an emission spectrum with a peak at 340 nm characteristic of a tryptophan residue. The emission with a peak at 307 nm is considered to arise from the tryrosine residues. The tryptophan quantum yield of Streptomyces subtilisin inhibitor excited at 295 nm is very small, indicating that the tryptophan florescence is strongly quenched in the native state of the inhibitor. Below pH 4 the peak of the fluorescence spectrum of the inhibitor excited at 280 nm shifts toward 340-350 nm with a concomitant increase in the quantum yield. The structural change induced by low pH seems to release the tryptophan fluorescence from the quenching.", "contents": "An unusual fluorescence spectrum of a protein proteinase inhibitor, Streptomyces subtilisin inhibitor. Streptomyces subtilisin inhibitor, a dimeric protein proteinase inhibitor isolated in crystalline form by Murae et al. in 1972, contains three tyrosine and one tryptophan residues per monomer unit and has unusual fluorescence properties. When excited at 280 nm, it shows a characteristic fluorescence spectrum having a peak at 307 nm and a shoulder near 340 nm, a feature which has been recognized only for a very few cases in proteins containing both tryosine and tryptophan residues. When excited at 295 nm, at which tryrosine scarcely absorbs, the inhibitor shows an emission spectrum with a peak at 340 nm characteristic of a tryptophan residue. The emission with a peak at 307 nm is considered to arise from the tryrosine residues. The tryptophan quantum yield of Streptomyces subtilisin inhibitor excited at 295 nm is very small, indicating that the tryptophan florescence is strongly quenched in the native state of the inhibitor. Below pH 4 the peak of the fluorescence spectrum of the inhibitor excited at 280 nm shifts toward 340-350 nm with a concomitant increase in the quantum yield. The structural change induced by low pH seems to release the tryptophan fluorescence from the quenching."}
{"id": "PMID:11831", "title": "Structure-activity relationships of luliberin substituted at position 8.", "content": "Substitution of arginine at position 8 of luliberin by the basic amino acids homoarginine, lysine and diaminobutyric acid resulted in analogues in which the luteinizing hormone-releasing activity is markedly reduced, whereas the cross reactivity with specific antibodies to luliberin is preserved. Fluorimetric titrations of these analogues, carried out as with luliberin, revealed pK values of 6.00 +/- 0.05 and of 9.75 +/- 0.15 for His 2 and Try 5 respectively which are essentially the same as in luliberin. However, the rate of collisions between the side chains of His 2 and Trp 3 in these analogues was found to decrease by 36-39%. Substitution at position 8 with the non-basic amino acid omega-nitro arginine yielded an analogue possessing a very low hormonal activity as well as poor recognition of antibodies specific to luliberin. The fluorescence properties of this peptide are markedly different from those of luliberin and its three basic analogues. These results indicate that the functional integrity of the active unit His 2 . . . Tyr 5 . . . Arg 8 in luliberin depends both on size and basicity of the amino acid side chain at position 8.", "contents": "Structure-activity relationships of luliberin substituted at position 8. Substitution of arginine at position 8 of luliberin by the basic amino acids homoarginine, lysine and diaminobutyric acid resulted in analogues in which the luteinizing hormone-releasing activity is markedly reduced, whereas the cross reactivity with specific antibodies to luliberin is preserved. Fluorimetric titrations of these analogues, carried out as with luliberin, revealed pK values of 6.00 +/- 0.05 and of 9.75 +/- 0.15 for His 2 and Try 5 respectively which are essentially the same as in luliberin. However, the rate of collisions between the side chains of His 2 and Trp 3 in these analogues was found to decrease by 36-39%. Substitution at position 8 with the non-basic amino acid omega-nitro arginine yielded an analogue possessing a very low hormonal activity as well as poor recognition of antibodies specific to luliberin. The fluorescence properties of this peptide are markedly different from those of luliberin and its three basic analogues. These results indicate that the functional integrity of the active unit His 2 . . . Tyr 5 . . . Arg 8 in luliberin depends both on size and basicity of the amino acid side chain at position 8."}
{"id": "PMID:11832", "title": "Purification from baker's yeast of an activator of DNA photolyase.", "content": "The activity of purified DNA photolyase from Baker's yeast is enhanced by a compound (Activator (III)) obtained from yeast by chloroform extraction ion exchange chromatography and gel filtration. Thin layer chromatography and spectral data indicate that the compound is homogeneous. Activator III emits at 350 and 440 nm when excited at 290 nm, and emits at 440 nm when excited at 358 nm. After acid hydrolysis, emission at 440 nm is produced only by excitation at 358 nm, indicating that activator (III) contains two separate chromophoric moieties. The chromophore excited by 358 nm light has a pK of 9-11, while the other chromophore has a pK of 4-5, and possibly of 9-11. The enhancement of photolytic activity by activator (III) at a concentration equimolar with that of the enzyme and the similarity of the fluorescent spectra of the activator with that of heat-denatured photolyase, suggests that the activator may be the chromophore associated with the enzyme.", "contents": "Purification from baker's yeast of an activator of DNA photolyase. The activity of purified DNA photolyase from Baker's yeast is enhanced by a compound (Activator (III)) obtained from yeast by chloroform extraction ion exchange chromatography and gel filtration. Thin layer chromatography and spectral data indicate that the compound is homogeneous. Activator III emits at 350 and 440 nm when excited at 290 nm, and emits at 440 nm when excited at 358 nm. After acid hydrolysis, emission at 440 nm is produced only by excitation at 358 nm, indicating that activator (III) contains two separate chromophoric moieties. The chromophore excited by 358 nm light has a pK of 9-11, while the other chromophore has a pK of 4-5, and possibly of 9-11. The enhancement of photolytic activity by activator (III) at a concentration equimolar with that of the enzyme and the similarity of the fluorescent spectra of the activator with that of heat-denatured photolyase, suggests that the activator may be the chromophore associated with the enzyme."}
{"id": "PMID:11833", "title": "Altered leucyl-transfer RNA synthetase from a mammalian cell culture mutant.", "content": "Altered leucyl-tRNA synthetase from a mammalian cell culture temperature-sensitive mutant, tsHl, was compared with enzyme from normal wild type Chinese hamster ovary cells. The mutant enzyme had a Km for leucine four times larger than that of wild type and enzyme levels 3-10% that of wild type. The presence of tRNA was necessary during in vitro heating of the mutant enzyme to allow expression of thermolability while the presence of tRNA protected wild type enzyme against thermal inactivation. The tsHl enzyme was stable when heated alone or in the presence of tRNA, leucine, and ATP simultaneously. The mutant's enzymes aminoacylated tRNALeu, tRNAVal, and tRNAIle with fidelity in vitro as determined by cochromatography of the amino-acyl-tRNA isoacceptors on RPC-5 reversed phase chromatography. The mutant failed to show any defect other than the direct formation of leucyl tRNALeu by leucyl-tRNA synthetase.", "contents": "Altered leucyl-transfer RNA synthetase from a mammalian cell culture mutant. Altered leucyl-tRNA synthetase from a mammalian cell culture temperature-sensitive mutant, tsHl, was compared with enzyme from normal wild type Chinese hamster ovary cells. The mutant enzyme had a Km for leucine four times larger than that of wild type and enzyme levels 3-10% that of wild type. The presence of tRNA was necessary during in vitro heating of the mutant enzyme to allow expression of thermolability while the presence of tRNA protected wild type enzyme against thermal inactivation. The tsHl enzyme was stable when heated alone or in the presence of tRNA, leucine, and ATP simultaneously. The mutant's enzymes aminoacylated tRNALeu, tRNAVal, and tRNAIle with fidelity in vitro as determined by cochromatography of the amino-acyl-tRNA isoacceptors on RPC-5 reversed phase chromatography. The mutant failed to show any defect other than the direct formation of leucyl tRNALeu by leucyl-tRNA synthetase."}
{"id": "PMID:11834", "title": "Glucose 6-phosphate-dependent binding of hexokinase to membranes of ascites tumor cells.", "content": "A pH-dependent, saturable binding of hexokinase isozyme I from Ehrlich ascites carcinoma to plasma membrane and microsome preparations from the same tissue is demonstrated. This binding is enhanced by glucose 6-phosphate and may be considered as the sum of a glucose 6-phosphate-dependent binding and an independent binding. The half saturation concentration of hexokinase is about 0.4 unit per ml for both types of binding, and a maximal binding of 0.5-2.0 units per mg membrane protein is observed for both, although the pH optimum of the independent binding (5.4) is lower than that of the dependent binding (5.9). The half saturation concentration of glucose 6-phosphate required for the dependent binding is 0.05 mM at pH 6.1. 2-Deoxyglucose 6-phosphate competatively reverses the effect of glucose 6-phosphate on binding but does not diminish its inhibition of hexokinase activity.", "contents": "Glucose 6-phosphate-dependent binding of hexokinase to membranes of ascites tumor cells. A pH-dependent, saturable binding of hexokinase isozyme I from Ehrlich ascites carcinoma to plasma membrane and microsome preparations from the same tissue is demonstrated. This binding is enhanced by glucose 6-phosphate and may be considered as the sum of a glucose 6-phosphate-dependent binding and an independent binding. The half saturation concentration of hexokinase is about 0.4 unit per ml for both types of binding, and a maximal binding of 0.5-2.0 units per mg membrane protein is observed for both, although the pH optimum of the independent binding (5.4) is lower than that of the dependent binding (5.9). The half saturation concentration of glucose 6-phosphate required for the dependent binding is 0.05 mM at pH 6.1. 2-Deoxyglucose 6-phosphate competatively reverses the effect of glucose 6-phosphate on binding but does not diminish its inhibition of hexokinase activity."}
{"id": "PMID:11835", "title": "Plasma membrane phosphorylation by endogenous phosphate donors in human blood platelets. Selectivity of the action of dibutyryl cyclic AMP.", "content": "Incubation of platelet-rich plasma with 32Pi leads to cellular uptake of the isotope and covalent incorporation into several cell constituents. Plasma membranes isolated from intact labelled platelets, delipidated and solubilized in sodium dodecyl sulfate, show, upon gel electorphoretic analysis, three main peaks of radioactivity: two in the molecular weight range 100 000-30 000 and an additional very slow migrating component strong positive by the peirodic acid-Schiff reaction. Treatment of the cells with dibutyryl cyclic AMP under conditions just sufficient to completely inhibit platelet aggregation leads to an increased isotope incorporation. Electrophoretic analysis of membranes isolated from dibutyryl cyclic AMP-treated cell reveals: (a) no change in the general pattern of distribution of the isotope, (b) no difference in the isotope incorporation to the two components of lower mol. wt. and (c) a marked increase (greater than 100%) in isotope incorporation in the slow migrating material as compared to membranes isolated from control cells. This material can be extracted from platelet plasma membranes after treatment of the membranes for 5 h with Triton X-100, at a detergent-to-protein ratio of 7.5. When the membrane material extracted with Triton X-100 is subjected to gel chromatography in Agarose (Biogel A-15m), the phosphorylated material that corresponds to the slow migrating band in polyacrylanide gel electrophoresis is eluted with or very close to the void volume of the column. Isoelectric focussing of this fraction, shows a single radioactive peak corresponding to an isolectric point of 3.78. The isolated component is pronase-sensitive, contains 52% of carbohydrate and 15% sialic acid. Analysis of the stability of the bound phosphate suggests that about 43% of it is bound as acyl-phosphate. The results reported, obtained through an approach that closely resembles physiological conditions are compatible with the participation of this membrane phosphoglycoprotein in the phenomena of platelet aggregation.", "contents": "Plasma membrane phosphorylation by endogenous phosphate donors in human blood platelets. Selectivity of the action of dibutyryl cyclic AMP. Incubation of platelet-rich plasma with 32Pi leads to cellular uptake of the isotope and covalent incorporation into several cell constituents. Plasma membranes isolated from intact labelled platelets, delipidated and solubilized in sodium dodecyl sulfate, show, upon gel electorphoretic analysis, three main peaks of radioactivity: two in the molecular weight range 100 000-30 000 and an additional very slow migrating component strong positive by the peirodic acid-Schiff reaction. Treatment of the cells with dibutyryl cyclic AMP under conditions just sufficient to completely inhibit platelet aggregation leads to an increased isotope incorporation. Electrophoretic analysis of membranes isolated from dibutyryl cyclic AMP-treated cell reveals: (a) no change in the general pattern of distribution of the isotope, (b) no difference in the isotope incorporation to the two components of lower mol. wt. and (c) a marked increase (greater than 100%) in isotope incorporation in the slow migrating material as compared to membranes isolated from control cells. This material can be extracted from platelet plasma membranes after treatment of the membranes for 5 h with Triton X-100, at a detergent-to-protein ratio of 7.5. When the membrane material extracted with Triton X-100 is subjected to gel chromatography in Agarose (Biogel A-15m), the phosphorylated material that corresponds to the slow migrating band in polyacrylanide gel electrophoresis is eluted with or very close to the void volume of the column. Isoelectric focussing of this fraction, shows a single radioactive peak corresponding to an isolectric point of 3.78. The isolated component is pronase-sensitive, contains 52% of carbohydrate and 15% sialic acid. Analysis of the stability of the bound phosphate suggests that about 43% of it is bound as acyl-phosphate. The results reported, obtained through an approach that closely resembles physiological conditions are compatible with the participation of this membrane phosphoglycoprotein in the phenomena of platelet aggregation."}
{"id": "PMID:11836", "title": "[Purification and properties of rat kidney catechol-O-methyltransferase].", "content": "The S-adenosyl-methionine: catechol-O-methyltransferase (EC 2.1.1.6) from rat kidney was purified about 650 fold as compared with the homogenate and the result of disc electrophoresis presented. The purification involved extraction, precipitation at pH 5, ammonium sulfate fractionation, Chromatographies on Biogel 0.5 m, Ultrogel AcA 44 and DE Sephadex A 50. Affinity chromatography was tried but unsuccessful. The enzyme exhibited two pH optima at 7.9 and 9.6 with a minimum at about 8.9. The COMT had a temperature optimum of 50 degrees C, with activation energy of 23.1 Kcal/Mole between 25-35 degrees C, 18.9 Kcal/mole between 35-45 degrees C and the Q10 within the range of 25-35 degrees amounted to 3.5. The molecular weight was estimated to be 21500+/-1000 daltons from its behavior on Ultrogel AcA 44 and the pH1 determined by electrofocalisation was near 5.50. The time of half life of the best purified enzymatic extract was found to be 2 h 10 min. at -20 degrees C. At basic pH the instability of the enzyme was increased. Since O-methylation required the presence of divalent cations, our results show that apparent Michaelis constants for Mg++ and Mn++ were respectively 0.50 X 10(-3) M and 0.33 X 10(-5) M. The study of their Hill's number indicated that there was only one point of fixation on the enzyme. The Km value determined by Florini and Vestling's method were 2.5 X 10(-4) M and 11.9 X 10(-5) M for epinephrine and S-adenosyl-methionine respectively. All results were discussed with respect to other investigations.", "contents": "[Purification and properties of rat kidney catechol-O-methyltransferase]. The S-adenosyl-methionine: catechol-O-methyltransferase (EC 2.1.1.6) from rat kidney was purified about 650 fold as compared with the homogenate and the result of disc electrophoresis presented. The purification involved extraction, precipitation at pH 5, ammonium sulfate fractionation, Chromatographies on Biogel 0.5 m, Ultrogel AcA 44 and DE Sephadex A 50. Affinity chromatography was tried but unsuccessful. The enzyme exhibited two pH optima at 7.9 and 9.6 with a minimum at about 8.9. The COMT had a temperature optimum of 50 degrees C, with activation energy of 23.1 Kcal/Mole between 25-35 degrees C, 18.9 Kcal/mole between 35-45 degrees C and the Q10 within the range of 25-35 degrees amounted to 3.5. The molecular weight was estimated to be 21500+/-1000 daltons from its behavior on Ultrogel AcA 44 and the pH1 determined by electrofocalisation was near 5.50. The time of half life of the best purified enzymatic extract was found to be 2 h 10 min. at -20 degrees C. At basic pH the instability of the enzyme was increased. Since O-methylation required the presence of divalent cations, our results show that apparent Michaelis constants for Mg++ and Mn++ were respectively 0.50 X 10(-3) M and 0.33 X 10(-5) M. The study of their Hill's number indicated that there was only one point of fixation on the enzyme. The Km value determined by Florini and Vestling's method were 2.5 X 10(-4) M and 11.9 X 10(-5) M for epinephrine and S-adenosyl-methionine respectively. All results were discussed with respect to other investigations."}
{"id": "PMID:11837", "title": "Purification and some properties of free and cell-associated dextransucrase from Streptococcus sanguis.", "content": "Dextransucrase of Streptococcus sanguis occurred in cell-free and cell-associated forms. Cell-free dextransucrase was purified by four successive chromatographies on Bio-Gel P 60, DEAE-cellulose, and Bio-Gel P 200 from the culture supernatant. The purification of cell-associated dextransucrase was made from the pellet of Streptococcus sanguis culture. Bacterial pellet was extracted with 1 M phosphate buffer (pH 6.0) and chromatographied by using an immunosorbent column. The two enzymes gave single bands in polyacrylamide gel electrophoresis. The molecular weight determined by sodium dodecyl sulfate polyacrylamide gel was about 100 000 daltons for the two forms of dextransucrases. The optimum pH of the cell-free and cell-associated enzymes was around 6 and the temperature optimum was broad for the two enzymes. The KM values for sucrose were respectively 2 mM and 3 mM for cell-free and cell-associated enzymes. When primer dextran was added, the reaction velocity increased but the KM for sucrose remained the same, and the KA for dextran was 200 muM for the two dextransucrases. Trehalose and maltose acted also as glucosyl residue acceptors. Purified enzymes had dextran synthesising activity and invertase-like activity. The same properties of the two forms of enzymes and the positive cross reaction against anti free and anti cell-associated globulins stongly suggest the identity of the two enzymes.", "contents": "Purification and some properties of free and cell-associated dextransucrase from Streptococcus sanguis. Dextransucrase of Streptococcus sanguis occurred in cell-free and cell-associated forms. Cell-free dextransucrase was purified by four successive chromatographies on Bio-Gel P 60, DEAE-cellulose, and Bio-Gel P 200 from the culture supernatant. The purification of cell-associated dextransucrase was made from the pellet of Streptococcus sanguis culture. Bacterial pellet was extracted with 1 M phosphate buffer (pH 6.0) and chromatographied by using an immunosorbent column. The two enzymes gave single bands in polyacrylamide gel electrophoresis. The molecular weight determined by sodium dodecyl sulfate polyacrylamide gel was about 100 000 daltons for the two forms of dextransucrases. The optimum pH of the cell-free and cell-associated enzymes was around 6 and the temperature optimum was broad for the two enzymes. The KM values for sucrose were respectively 2 mM and 3 mM for cell-free and cell-associated enzymes. When primer dextran was added, the reaction velocity increased but the KM for sucrose remained the same, and the KA for dextran was 200 muM for the two dextransucrases. Trehalose and maltose acted also as glucosyl residue acceptors. Purified enzymes had dextran synthesising activity and invertase-like activity. The same properties of the two forms of enzymes and the positive cross reaction against anti free and anti cell-associated globulins stongly suggest the identity of the two enzymes."}
{"id": "PMID:11838", "title": "[Primary structure of bovine erythrocyte carbonic anhydrase CI. I. Tryptic peptides].", "content": "Bovine erythrocyte carbonic anhydrase CI consists of 259 amino acid residues including 18 lysines and 9 arginines. Its primary structure has been first investigated by isolation and sequence determination of the tryptic units. Acidification of the tryptic hydrolysate leads to the precipitation of 40% of the peptidic material. All the acid soluble peptides were isolated from the supernatant by chromatography on Dowex 50 W-X2 and Dowex 1-X2 followed by purification of heterogeneous fractions. Two of the three  acid insoluble peptides were obtained in a pure form from the whole tryptic hydrolysate by gel filtration on Sephadex G-50 and chromatography on DEAE-Sephadex in alkaline medium. The sequence of the so isolated tryptic units has been determined with the exception of two of them obtained in a very poor yield.", "contents": "[Primary structure of bovine erythrocyte carbonic anhydrase CI. I. Tryptic peptides]. Bovine erythrocyte carbonic anhydrase CI consists of 259 amino acid residues including 18 lysines and 9 arginines. Its primary structure has been first investigated by isolation and sequence determination of the tryptic units. Acidification of the tryptic hydrolysate leads to the precipitation of 40% of the peptidic material. All the acid soluble peptides were isolated from the supernatant by chromatography on Dowex 50 W-X2 and Dowex 1-X2 followed by purification of heterogeneous fractions. Two of the three  acid insoluble peptides were obtained in a pure form from the whole tryptic hydrolysate by gel filtration on Sephadex G-50 and chromatography on DEAE-Sephadex in alkaline medium. The sequence of the so isolated tryptic units has been determined with the exception of two of them obtained in a very poor yield."}
{"id": "PMID:11839", "title": "The shikimate pathway. III. 3-dehydroquinate synthetase of E. coli. Mechanistic studies by kinetic isotope effect.", "content": "The conversion of 3-deoxy D-arabino heptulosonate 7-phosphate to 3-dehydroquinate by the 3-dehydroquinate synthetase from E. coli is characterized by a low but significant kinetic isotope effect for tritium carried in position-5 of DAHP, while no isotope effect was detectable for tritium in position-4. This effect was observed at different pH nad is interpreted as a result of theintermediary of a 5-ketonic form of the substrate, formed in a preliminary non limiting step during the enzymic cyclization reaction. A tentative scheme for the 3-DHQ synthetase reaction is proposed involving five steps: oxidation by NAD+ in position-5, phsophate elimination after enolization, reduction with precedently formed NADH and cyclization by attack of the 2-carbonyl by the C-7 methylene group.", "contents": "The shikimate pathway. III. 3-dehydroquinate synthetase of E. coli. Mechanistic studies by kinetic isotope effect. The conversion of 3-deoxy D-arabino heptulosonate 7-phosphate to 3-dehydroquinate by the 3-dehydroquinate synthetase from E. coli is characterized by a low but significant kinetic isotope effect for tritium carried in position-5 of DAHP, while no isotope effect was detectable for tritium in position-4. This effect was observed at different pH nad is interpreted as a result of theintermediary of a 5-ketonic form of the substrate, formed in a preliminary non limiting step during the enzymic cyclization reaction. A tentative scheme for the 3-DHQ synthetase reaction is proposed involving five steps: oxidation by NAD+ in position-5, phsophate elimination after enolization, reduction with precedently formed NADH and cyclization by attack of the 2-carbonyl by the C-7 methylene group."}
{"id": "PMID:11840", "title": "[Mechanism of opiate of oxidative phosphorylation in mitochondria].", "content": "Effect of morphine, codeine, dionine and nalorphine on the oxidative phosphorylation in rat liver mitochondria was studied. Morphine is found to inhibit both ATP-synthetase and ATP-ase activities in mitochondria, but not in submitochondrial particles. Morphine-suppressed oxidative phosphorylation was competitively reversed with high concentrations of ADP, but not of inorganic phosphate. The effect of other opiates (i.e. codeine, dionine, nalorphine) was similar. It is suggested, that opiates inhibit the transport of adenine nucleotides through inner mitochondrial membrane, as it does atractyloside. A significance of the hydrophobic interaction between the inhibitor and adenine nucleotide translocase is outlined, since the degree of the inhibition of oxidative phosphorylation is increased with the increase in the number of non-ionized opiate molecules (at alkaline pH values) and in the length of the carbon chain of narcotic molecule as follows: morphine--codeine--dionine--nalorphine.", "contents": "[Mechanism of opiate of oxidative phosphorylation in mitochondria]. Effect of morphine, codeine, dionine and nalorphine on the oxidative phosphorylation in rat liver mitochondria was studied. Morphine is found to inhibit both ATP-synthetase and ATP-ase activities in mitochondria, but not in submitochondrial particles. Morphine-suppressed oxidative phosphorylation was competitively reversed with high concentrations of ADP, but not of inorganic phosphate. The effect of other opiates (i.e. codeine, dionine, nalorphine) was similar. It is suggested, that opiates inhibit the transport of adenine nucleotides through inner mitochondrial membrane, as it does atractyloside. A significance of the hydrophobic interaction between the inhibitor and adenine nucleotide translocase is outlined, since the degree of the inhibition of oxidative phosphorylation is increased with the increase in the number of non-ionized opiate molecules (at alkaline pH values) and in the length of the carbon chain of narcotic molecule as follows: morphine--codeine--dionine--nalorphine."}
{"id": "PMID:11841", "title": "[Regulation of urocaninase activity in the liver: role of 3',5'-AMP].", "content": "A dependence of rat liver urocaninase activity on the agents affecting the adenylate cyclase system was studied in vitro and in vivo. Urocaninase is considerably activated after the injection of glucagone, NaF, theophylline and 3',5'-AMP. Under conditions optimal for the protein kinase activity of phosphorylase the urocaninase of liver extracts was activated 7-fold on the average. The nezyme retains its activity after gel-filtration through Sephadex G-25 and is capable of inactivation in the presence of Mg2+ and of reactivation after addition of ATP and 3',5'-AMP. These data suggest a possibility of regulation of mammalian liver urocaninase activity by 3',5'-AMP-dependent phosphorylation of the enzyme. Derivatives of hypoxanthine (theophylline and caffeine) in concentration 10(-4) M activate urocaninase in liver extracts 2--3 and 1.5-fold respectively. The activation is probably not due to the 3',5'-AMP phosphodiesterase inhibition, since another phosphodiesterase inhibitor--papaverine--has no activating effect on urocaninase.", "contents": "[Regulation of urocaninase activity in the liver: role of 3',5'-AMP]. A dependence of rat liver urocaninase activity on the agents affecting the adenylate cyclase system was studied in vitro and in vivo. Urocaninase is considerably activated after the injection of glucagone, NaF, theophylline and 3',5'-AMP. Under conditions optimal for the protein kinase activity of phosphorylase the urocaninase of liver extracts was activated 7-fold on the average. The nezyme retains its activity after gel-filtration through Sephadex G-25 and is capable of inactivation in the presence of Mg2+ and of reactivation after addition of ATP and 3',5'-AMP. These data suggest a possibility of regulation of mammalian liver urocaninase activity by 3',5'-AMP-dependent phosphorylation of the enzyme. Derivatives of hypoxanthine (theophylline and caffeine) in concentration 10(-4) M activate urocaninase in liver extracts 2--3 and 1.5-fold respectively. The activation is probably not due to the 3',5'-AMP phosphodiesterase inhibition, since another phosphodiesterase inhibitor--papaverine--has no activating effect on urocaninase."}
{"id": "PMID:11842", "title": "[Effect of environmental factors on inactivation of B12-dependent glycerol dehydratase from Aerobacter aerogenes].", "content": "Effect of temperature, pH and univalent cation on kinetics of self-activation of B12-dependent glycerol dehydratase (GD) from Aerobacter aerogenes with Co alpha-[alpha-(5,6-dimethylbenzimidazolyl]-Co beta-adenosylcobamide (AdoCbl) was investigated. The activation energy of the process of GD inactivation is found to be 3.9 kkal/M, the effect of pH on GD inactivation being insignificant. Monovalent cation is not required for the formation of GD-AdoCbl complex, but it protects the complex from selfinactivation. The rate of GD inactivation greatly depends on concentration of monovalent cations. Effect of K+, Rb+, Cs+, Tl+ and NH4+ cations, which are enzyme cofactors, qualitatively differs from the effect of Na+ and Li+, which are inactive in a catalytic reaction. The presence of at least two cation-binding sites in GD molecule is suggested. Possible mechanism of the effect of environmental factors in self-inactivation of GD-AdoCbl complex is discussed.", "contents": "[Effect of environmental factors on inactivation of B12-dependent glycerol dehydratase from Aerobacter aerogenes]. Effect of temperature, pH and univalent cation on kinetics of self-activation of B12-dependent glycerol dehydratase (GD) from Aerobacter aerogenes with Co alpha-[alpha-(5,6-dimethylbenzimidazolyl]-Co beta-adenosylcobamide (AdoCbl) was investigated. The activation energy of the process of GD inactivation is found to be 3.9 kkal/M, the effect of pH on GD inactivation being insignificant. Monovalent cation is not required for the formation of GD-AdoCbl complex, but it protects the complex from selfinactivation. The rate of GD inactivation greatly depends on concentration of monovalent cations. Effect of K+, Rb+, Cs+, Tl+ and NH4+ cations, which are enzyme cofactors, qualitatively differs from the effect of Na+ and Li+, which are inactive in a catalytic reaction. The presence of at least two cation-binding sites in GD molecule is suggested. Possible mechanism of the effect of environmental factors in self-inactivation of GD-AdoCbl complex is discussed."}
{"id": "PMID:11843", "title": "[Regulation of glutamine metabolism in Chlorella pyrenoidosa. Mechanisms of regulating the activity of glutamine synthetase during ammonia assimilation].", "content": "Glutamine synthetase (GS) (E.C.6.3.1.2) activity in Chlorella cells decreased when NH4+ was added to nitrogen-free growth medium. This GS inactivation had such a rate, that it could not be due to the repression of enzyme synthesis: the GS activity decreased by 20% within 5 minutes of NH4+ assimilation. Glutamine content in cell increased in 2.5 times for this period. In vitro experiments have shown that glutamine is a strong inhibitor of GS from Chlorella grown in the presence of NO3-, and in a less degree--an inhibitor of GS from cells grown in ammonium-containing medium. The data obtained are negative with respect to possible mechanisms of GS activity regulation via adenylation and ATP-dependent destruction of glutamine synthetase.", "contents": "[Regulation of glutamine metabolism in Chlorella pyrenoidosa. Mechanisms of regulating the activity of glutamine synthetase during ammonia assimilation]. Glutamine synthetase (GS) (E.C.6.3.1.2) activity in Chlorella cells decreased when NH4+ was added to nitrogen-free growth medium. This GS inactivation had such a rate, that it could not be due to the repression of enzyme synthesis: the GS activity decreased by 20% within 5 minutes of NH4+ assimilation. Glutamine content in cell increased in 2.5 times for this period. In vitro experiments have shown that glutamine is a strong inhibitor of GS from Chlorella grown in the presence of NO3-, and in a less degree--an inhibitor of GS from cells grown in ammonium-containing medium. The data obtained are negative with respect to possible mechanisms of GS activity regulation via adenylation and ATP-dependent destruction of glutamine synthetase."}
{"id": "PMID:11844", "title": "[Isolation and several properties of purified preparations of the alkaline ribonuclease of the soluble fraction of rat cerebral hemispheres].", "content": "Preparations of alkaline ribonuclease with optimum activity at pH 7,8 have been isolated from postmitochondrial fraction of the rat brain tissue by ammonium sulfate precipitation, 0.1 HCl extraction and following ammonium sulfate fractionation. Two preparations of this enzyme have been obtained by gel filtration through Sephadex G-25 and G-75, molecular weight of one of them (the most purified preparation) being about 13000. During electrophoresis the preparations moved from anode to cathode through polyacrylamide gel at pH 3.2. Bivalent cations (Ca2+, Mg2+) activated the enzyme preparations at concentration of u.10(-3)--5.10(-3) M. The degree of purification of preparations examined was 60 and 250 respectively.", "contents": "[Isolation and several properties of purified preparations of the alkaline ribonuclease of the soluble fraction of rat cerebral hemispheres]. Preparations of alkaline ribonuclease with optimum activity at pH 7,8 have been isolated from postmitochondrial fraction of the rat brain tissue by ammonium sulfate precipitation, 0.1 HCl extraction and following ammonium sulfate fractionation. Two preparations of this enzyme have been obtained by gel filtration through Sephadex G-25 and G-75, molecular weight of one of them (the most purified preparation) being about 13000. During electrophoresis the preparations moved from anode to cathode through polyacrylamide gel at pH 3.2. Bivalent cations (Ca2+, Mg2+) activated the enzyme preparations at concentration of u.10(-3)--5.10(-3) M. The degree of purification of preparations examined was 60 and 250 respectively."}
{"id": "PMID:11845", "title": "[Alpha-glucosidase from human kidneys].", "content": "The data obtained show that most part of the activity of neutral alpha-glucosidases from human kidney is observed in the particle fraction, and only approximately 15%--in supernatant. Soluble neutral alpha-glucosidases have at least 4 different forms, as it is shown by means of their fractionation on Sephadex G-150, Bio-Gel P-200 and by polyacrylamide gel electrophoresis. Four forms are different in their molecular weight, electrophoretic mobility and substrate specificity. Two of the forms have molecular weight of 310000 and 110000. All the neutral alpha-glucosidases except high molecular weight form (greater than 400000) were retarded on column of Sephadex G-150.", "contents": "[Alpha-glucosidase from human kidneys]. The data obtained show that most part of the activity of neutral alpha-glucosidases from human kidney is observed in the particle fraction, and only approximately 15%--in supernatant. Soluble neutral alpha-glucosidases have at least 4 different forms, as it is shown by means of their fractionation on Sephadex G-150, Bio-Gel P-200 and by polyacrylamide gel electrophoresis. Four forms are different in their molecular weight, electrophoretic mobility and substrate specificity. Two of the forms have molecular weight of 310000 and 110000. All the neutral alpha-glucosidases except high molecular weight form (greater than 400000) were retarded on column of Sephadex G-150."}
{"id": "PMID:11848", "title": "Effect of osmotic changes on intracellular pH and haemoglobin oxygen affinity of human erythrocytes.", "content": "The effect of osmolality on intra-erythrocytic pH and haemoglobin oxygen affinity of red cells was studied at three different osmolality levels (the mean osmolalities were respectively 257, 294 and 341 mOsmol). No osmotically induced alteration of the pHe-pHi relationship was observed. In contrast, P50(7.4) increased (namely: 24.5, 24.9 and 25.6 torr) as osmolality rose. This increase was accompanied by a simultaneous increment of both MCHC (respectively 30.5, 33.4 and 36.3 g percent) and 2,3-DPG concentration (4.495, 4.924 and 5.392 mM/l red cells) while the 2,3-DPG/Hb molar ratio remained constant. The different factors that might induce such a change in haemoglobin affinity for oxygen were discussed. It would be best explained by a modification in the amount of haemoglobin-bound 2,3-DPG when 2,3-DPG and haemoglobin concentrations in red cell vary simultaneously.", "contents": "Effect of osmotic changes on intracellular pH and haemoglobin oxygen affinity of human erythrocytes. The effect of osmolality on intra-erythrocytic pH and haemoglobin oxygen affinity of red cells was studied at three different osmolality levels (the mean osmolalities were respectively 257, 294 and 341 mOsmol). No osmotically induced alteration of the pHe-pHi relationship was observed. In contrast, P50(7.4) increased (namely: 24.5, 24.9 and 25.6 torr) as osmolality rose. This increase was accompanied by a simultaneous increment of both MCHC (respectively 30.5, 33.4 and 36.3 g percent) and 2,3-DPG concentration (4.495, 4.924 and 5.392 mM/l red cells) while the 2,3-DPG/Hb molar ratio remained constant. The different factors that might induce such a change in haemoglobin affinity for oxygen were discussed. It would be best explained by a modification in the amount of haemoglobin-bound 2,3-DPG when 2,3-DPG and haemoglobin concentrations in red cell vary simultaneously."}
{"id": "PMID:11849", "title": "Lack of effect of methemoglobinemia on the plasma-erythrocyte pH relationship.", "content": "A stable and reproducible methemoglobinemia is induced by small concentration of an oxidizing gas (NO). Under such conditions we evidenced that plasma pH (pHe) to erythrocyte pH (pHi) relationship is unchanged. A strong acidity bound to the changes of NO in water occurs. But we may conclude that the buffer capacity of erythrocyte is not modified by the oxydation of ferro into ferrihemoglobin within the erythrocyte.", "contents": "Lack of effect of methemoglobinemia on the plasma-erythrocyte pH relationship. A stable and reproducible methemoglobinemia is induced by small concentration of an oxidizing gas (NO). Under such conditions we evidenced that plasma pH (pHe) to erythrocyte pH (pHi) relationship is unchanged. A strong acidity bound to the changes of NO in water occurs. But we may conclude that the buffer capacity of erythrocyte is not modified by the oxydation of ferro into ferrihemoglobin within the erythrocyte."}
{"id": "PMID:11850", "title": "Evidence of a pure \"contraction alkalosis= in awaken rat.", "content": "A pure contraction alkalosis with no urinary loss of bicarbonate was evidenced in awaken rat, after a Furosemide IV injection. We observed: 1) an early and important respiratory compensation possibly owing to a simultaneous contraction of CSF volume, thus increasing bicarbonate concentration. 2) a net shift of HCO3- towards intracellular compartment, in proportion to the magnitude of the contraction rather than to bicarbonate gradient across the membrane.", "contents": "Evidence of a pure \"contraction alkalosis= in awaken rat. A pure contraction alkalosis with no urinary loss of bicarbonate was evidenced in awaken rat, after a Furosemide IV injection. We observed: 1) an early and important respiratory compensation possibly owing to a simultaneous contraction of CSF volume, thus increasing bicarbonate concentration. 2) a net shift of HCO3- towards intracellular compartment, in proportion to the magnitude of the contraction rather than to bicarbonate gradient across the membrane."}
{"id": "PMID:11851", "title": "The effect of Trichinella spiralis on graft-versus-host reaction, transplantation immunity and antibody formation.", "content": "The effect of Trichinella spiralis in different phases of infection on transplantation immunity, the ability of lymphocytes to induce graft-versus-host reaction, on antibody and plaque-forming cell production was studied. In certain phases of Trichinella spiralis beginhing from the first days of infection and during 40 days significant suppression of transplantation immunity was observed. Thus, on the 24th day of infection skin allograft necrosis occurred much later (26.2 days) as compared with non-infected mice (12.5 days). The spleen cells of C57BL/6j mice infected with Trichinella spiralis on the 22, 29, 36, 42, 56, 72 days either induced slight graft-versus-host reaction in (CBA X C57B1/6j) F1 hybrid mice or did not induce it at all (42nd day of infection). The amount of antibody forming cells in Trichinella-infected mice significantly decreased on the 20, 25, 47, 55th days of infection. Hemagglutinin production to sheep red blood cells was significantly inhibited on the 25th day of Trichinella spiralis infection. The concept of immunodepressors being released from helminths is briefly discussed.", "contents": "The effect of Trichinella spiralis on graft-versus-host reaction, transplantation immunity and antibody formation. The effect of Trichinella spiralis in different phases of infection on transplantation immunity, the ability of lymphocytes to induce graft-versus-host reaction, on antibody and plaque-forming cell production was studied. In certain phases of Trichinella spiralis beginhing from the first days of infection and during 40 days significant suppression of transplantation immunity was observed. Thus, on the 24th day of infection skin allograft necrosis occurred much later (26.2 days) as compared with non-infected mice (12.5 days). The spleen cells of C57BL/6j mice infected with Trichinella spiralis on the 22, 29, 36, 42, 56, 72 days either induced slight graft-versus-host reaction in (CBA X C57B1/6j) F1 hybrid mice or did not induce it at all (42nd day of infection). The amount of antibody forming cells in Trichinella-infected mice significantly decreased on the 20, 25, 47, 55th days of infection. Hemagglutinin production to sheep red blood cells was significantly inhibited on the 25th day of Trichinella spiralis infection. The concept of immunodepressors being released from helminths is briefly discussed."}
{"id": "PMID:11852", "title": "Human serum albumin variants: determination and repartition of allotypes in 24 cases of bisalbuminemia observed in the French population.", "content": "Weitkamp et al. (1973) using starch gel electrophoresis in three different systems of buffers (pH 5, 5.6 and 6.9) distinguish at least 24 genetically determined variants. In the European area only seven variants have been observed. The study of 24 cases of bisalbuminemia observed in the french population by acetate electrophoresis at pH 8.6 and polyacrylamide agarose gel electrophoresis at pH 8.7 and pH 6.9 can distinguish three slower variants than the normal albumin. The most frequent variant is the B type observed in 16 cases. The other types are the Pollibauer type observed in 7 cases, and the Gainsville type in one case only. The incidence of these variants can be estimated to 0.7 p. 1000 individuals.", "contents": "Human serum albumin variants: determination and repartition of allotypes in 24 cases of bisalbuminemia observed in the French population. Weitkamp et al. (1973) using starch gel electrophoresis in three different systems of buffers (pH 5, 5.6 and 6.9) distinguish at least 24 genetically determined variants. In the European area only seven variants have been observed. The study of 24 cases of bisalbuminemia observed in the french population by acetate electrophoresis at pH 8.6 and polyacrylamide agarose gel electrophoresis at pH 8.7 and pH 6.9 can distinguish three slower variants than the normal albumin. The most frequent variant is the B type observed in 16 cases. The other types are the Pollibauer type observed in 7 cases, and the Gainsville type in one case only. The incidence of these variants can be estimated to 0.7 p. 1000 individuals."}
{"id": "PMID:11853", "title": "Erythrocyte pH in respiratory and metabolic acid-base disturbances. Studies on human blood in vitro.", "content": "The influence of oxygenation in respiratory and metabolic acid-base disturbances on erythocyte pH has been studied on normal human blood \"in vitro\". In physiological pH range, pHe-pHi relationship is the same for PCO2 variations at constant metabolic level and for metablic level variations at constant PCO2. A \"global\" pHe-pHi relationship has been calculated at 0 and 100% SO2. The oxygen-linked pH shift depends on pH level and PCO2 and is different in plasma and erythrocyte. From these results arise conclusions on pHi and pHe dependency, physiological role of saturation level of hemoglobin and conditions of P50 normalisation at pH 7.4.", "contents": "Erythrocyte pH in respiratory and metabolic acid-base disturbances. Studies on human blood in vitro. The influence of oxygenation in respiratory and metabolic acid-base disturbances on erythocyte pH has been studied on normal human blood \"in vitro\". In physiological pH range, pHe-pHi relationship is the same for PCO2 variations at constant metabolic level and for metablic level variations at constant PCO2. A \"global\" pHe-pHi relationship has been calculated at 0 and 100% SO2. The oxygen-linked pH shift depends on pH level and PCO2 and is different in plasma and erythrocyte. From these results arise conclusions on pHi and pHe dependency, physiological role of saturation level of hemoglobin and conditions of P50 normalisation at pH 7.4."}
{"id": "PMID:11854", "title": "Production of cellulase by Trichoderma.", "content": "The cellulase complex in T. viride is inducible. For large-scale enzyme production the fungus should be cultured on media containing cellulose. The cellulase enzymes are respressible. To produce and maintain best cellulase yields cultural conditions which lead to carbohydrate consumption in excess of cellular needs should be avoided. With the present mutant (QM9414) extracellular enzyme preparations having 1.6 FP units/ml and 1.6 mg protein/ml have been obtained within four to five days in submerged fermentation. Such preparations are capable of producing a 5% sugar solution when mixed with 10% ball milled cellulose and incubated 24 hr at 50 degrees C. Further improvements of cellulase yields are being sought by continued mutagenesis and increased nutrient levels in the growth medium.", "contents": "Production of cellulase by Trichoderma. The cellulase complex in T. viride is inducible. For large-scale enzyme production the fungus should be cultured on media containing cellulose. The cellulase enzymes are respressible. To produce and maintain best cellulase yields cultural conditions which lead to carbohydrate consumption in excess of cellular needs should be avoided. With the present mutant (QM9414) extracellular enzyme preparations having 1.6 FP units/ml and 1.6 mg protein/ml have been obtained within four to five days in submerged fermentation. Such preparations are capable of producing a 5% sugar solution when mixed with 10% ball milled cellulose and incubated 24 hr at 50 degrees C. Further improvements of cellulase yields are being sought by continued mutagenesis and increased nutrient levels in the growth medium."}
{"id": "PMID:11859", "title": "Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle.", "content": "Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5-96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.", "contents": "Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle. Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5-96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure."}
{"id": "PMID:11860", "title": "Total folate binding capacity of normal human plasma, and variations in uremia, cirrhosis, and pregnancy.", "content": "The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325  pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements.", "contents": "Total folate binding capacity of normal human plasma, and variations in uremia, cirrhosis, and pregnancy. The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325  pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements."}
{"id": "PMID:11861", "title": "Cardiovascular effects of dopamine after central administration into conscious cats.", "content": "Dopamine (30 and 45 mug) administered intracerebroventricular (i.c.v.) to a group of 10 conscious normotensive cats caused dose-related increases in blood pressure and heart rate. In 4 of these animals the initial cardiovascular stimulant effects of i.c.v. dopamine were followed by hypotension and bradycardia. 2 alpha-Methyldopamine (30 and 45 mug i.c.v.) produced qualitatively similar responses to dopamine except that the cardiovascular stimulant effects were smaller and the secondary depressant effects somewhat more prolonged. 3 Both stimulant and depressant effects of i.c.v. dopamine and alpha-methyldopamine were greatly inhibited by autonomic ganglion blockade or by adrenergic neurone blockade. 4 The cardiovascular stimulant effects of both i.c.v. dopamine and i.c.v. alpha-methyldopamine were selectively inhibited by beta-adrenoceptor blocking agents whilst the cardiovascular depressant effects of these substances were abolished by the alpha-adrenoceptor blocker phentolamine or by the dopamine-beta-hydroxylase inhibitor disulfiram. 5 Haloperidol by either i.c.v. or the intravenous route abolished both cardiovascular stimulant and depressant effects of i.c.v. dopamine, whilst pimozide by either route inhibited only the cardiovascular stimulant effects. 6 In 2 cats, injection of dopamine into the cisterna magna produced predominantly depressant effects on the cardiovascular system except with a higher dose which induced biphasic responses.", "contents": "Cardiovascular effects of dopamine after central administration into conscious cats. Dopamine (30 and 45 mug) administered intracerebroventricular (i.c.v.) to a group of 10 conscious normotensive cats caused dose-related increases in blood pressure and heart rate. In 4 of these animals the initial cardiovascular stimulant effects of i.c.v. dopamine were followed by hypotension and bradycardia. 2 alpha-Methyldopamine (30 and 45 mug i.c.v.) produced qualitatively similar responses to dopamine except that the cardiovascular stimulant effects were smaller and the secondary depressant effects somewhat more prolonged. 3 Both stimulant and depressant effects of i.c.v. dopamine and alpha-methyldopamine were greatly inhibited by autonomic ganglion blockade or by adrenergic neurone blockade. 4 The cardiovascular stimulant effects of both i.c.v. dopamine and i.c.v. alpha-methyldopamine were selectively inhibited by beta-adrenoceptor blocking agents whilst the cardiovascular depressant effects of these substances were abolished by the alpha-adrenoceptor blocker phentolamine or by the dopamine-beta-hydroxylase inhibitor disulfiram. 5 Haloperidol by either i.c.v. or the intravenous route abolished both cardiovascular stimulant and depressant effects of i.c.v. dopamine, whilst pimozide by either route inhibited only the cardiovascular stimulant effects. 6 In 2 cats, injection of dopamine into the cisterna magna produced predominantly depressant effects on the cardiovascular system except with a higher dose which induced biphasic responses."}
{"id": "PMID:11862", "title": "On the functional coupling of neurotransmitter uptake and release in brain.", "content": "1 Isolated synaptosomal fractions from mouse forebrains were incubated [14C]-gamma-aminobutyric acid ([14C]-GABA). Release of the accumulated label in high potassium solution was measured. 2 The fractional release dependent upon calcium was decreased by raising the concentration of [14C]-GABA during labeling but was not affected by altering the time allowed for labelling or the time between labelling and stimulation. 3 These data suggest that extracellular GABA gains rapid access to available intraterminal pools. The relative distribution of the accumulated GABA in differerent pools can be influenced by the concentration of GABA in the incubation medium but, once (stored\", there is no net redistribution of accumulated GABA in the absence of stimulation.", "contents": "On the functional coupling of neurotransmitter uptake and release in brain. 1 Isolated synaptosomal fractions from mouse forebrains were incubated [14C]-gamma-aminobutyric acid ([14C]-GABA). Release of the accumulated label in high potassium solution was measured. 2 The fractional release dependent upon calcium was decreased by raising the concentration of [14C]-GABA during labeling but was not affected by altering the time allowed for labelling or the time between labelling and stimulation. 3 These data suggest that extracellular GABA gains rapid access to available intraterminal pools. The relative distribution of the accumulated GABA in differerent pools can be influenced by the concentration of GABA in the incubation medium but, once (stored\", there is no net redistribution of accumulated GABA in the absence of stimulation."}
{"id": "PMID:11863", "title": "Antagonism by some antihistamines of the amino acid-evoked responses recorded from the lobster muscle fibre and the frog spinal cord.", "content": "1 The effects of some antihistamines on the lobster muscle fibre and the frog spinal cord were investigated using intracellular and extracellular recordings, respectively. 2. On lobster muscle, histamine H1-blockers reversibly antagonized responses to bath-applied glutamate, aspartate and quisqualate but not responses to gamma-aminobutyric acid (GABA). Iontophoretic glutamate potentials were also reduced. Histamine (up to 1 mM) had no effect on this preparation. 3 The H1-antagonists produced a small increase in muscle membrane conductance and a slight hyperpolarization. These effects were largely unchanged in a low C1- bathing solution. Procaine (1 mM) decreased membrane conductance and did not affect responses to GABA or glutamate. 4 The H2-antagonist burimamide blocked both glutamate and GABA-evoked responses on the lobster muscle without affecting resting potential or conductance. 5 In the frog cord, bath-applied histamine produced ventral root depolarizations and dorsal root hyperpolarizations (sometimes biphasic responses). These effects were reduced by tetrodotoxin (TTX) but not by antazoline (H1-blocker) or burimamide; the latter reversibly antagonized responses to both glutamate and GABA on TTX-treated cords while antazoline was ineffective. 6 It is suggested that antihistamines can act as non-specific amino acid antagonists by interacting at the level of the receptor-coupled ionophores.", "contents": "Antagonism by some antihistamines of the amino acid-evoked responses recorded from the lobster muscle fibre and the frog spinal cord. 1 The effects of some antihistamines on the lobster muscle fibre and the frog spinal cord were investigated using intracellular and extracellular recordings, respectively. 2. On lobster muscle, histamine H1-blockers reversibly antagonized responses to bath-applied glutamate, aspartate and quisqualate but not responses to gamma-aminobutyric acid (GABA). Iontophoretic glutamate potentials were also reduced. Histamine (up to 1 mM) had no effect on this preparation. 3 The H1-antagonists produced a small increase in muscle membrane conductance and a slight hyperpolarization. These effects were largely unchanged in a low C1- bathing solution. Procaine (1 mM) decreased membrane conductance and did not affect responses to GABA or glutamate. 4 The H2-antagonist burimamide blocked both glutamate and GABA-evoked responses on the lobster muscle without affecting resting potential or conductance. 5 In the frog cord, bath-applied histamine produced ventral root depolarizations and dorsal root hyperpolarizations (sometimes biphasic responses). These effects were reduced by tetrodotoxin (TTX) but not by antazoline (H1-blocker) or burimamide; the latter reversibly antagonized responses to both glutamate and GABA on TTX-treated cords while antazoline was ineffective. 6 It is suggested that antihistamines can act as non-specific amino acid antagonists by interacting at the level of the receptor-coupled ionophores."}
{"id": "PMID:11864", "title": "Excretion and metabolism of nikethamide in the horse.", "content": "It is well known that nikethamide (N,N-diethylnicotinamide, CoramineR) is metabolized very rapidly to nicotinamide. Hence, there is difficulty in proving that nikethamide has been used as a doping substance because nicotinamide is a normal physiological metabolite in the organism as well as a vitamin preparation. However, an intermediate metabolite (N-ethylnicotinamide) was found by us in the urine of horses treated with CoramineR. This was characterized by gas chromatography/mass spectrometry, and synthesized and identified as being N-ethylnicotinamide. The excretion and metabolism of nikethamide after intramuscular injection in the horse was followed using quantitative gas chromatography of urine extracts over a period of several hours and the results of these experiments are reported. Changes in urinary pH had no significant effect upon either the metabolism or rate of excretion of the drug.", "contents": "Excretion and metabolism of nikethamide in the horse. It is well known that nikethamide (N,N-diethylnicotinamide, CoramineR) is metabolized very rapidly to nicotinamide. Hence, there is difficulty in proving that nikethamide has been used as a doping substance because nicotinamide is a normal physiological metabolite in the organism as well as a vitamin preparation. However, an intermediate metabolite (N-ethylnicotinamide) was found by us in the urine of horses treated with CoramineR. This was characterized by gas chromatography/mass spectrometry, and synthesized and identified as being N-ethylnicotinamide. The excretion and metabolism of nikethamide after intramuscular injection in the horse was followed using quantitative gas chromatography of urine extracts over a period of several hours and the results of these experiments are reported. Changes in urinary pH had no significant effect upon either the metabolism or rate of excretion of the drug."}
{"id": "PMID:11865", "title": "The detection of doping agents in blood.", "content": "Gas chromatographic screening procedures have been evaluated which permit the detection of stimulants and sedatives in blood after administration of pharmacological doses. The techniques actually used in sample preparations and gas chromatographic work are presented as well as examples of pharmacokinetic studies and postive dope cases. The use of sensitive and selective detectors like the nigrogen-specific detector or a mass spectrometer is absolutely essential for routine work, as for non-specific detectors the number of \"false positives\" leads to an intolerable work load for the laboratory.", "contents": "The detection of doping agents in blood. Gas chromatographic screening procedures have been evaluated which permit the detection of stimulants and sedatives in blood after administration of pharmacological doses. The techniques actually used in sample preparations and gas chromatographic work are presented as well as examples of pharmacokinetic studies and postive dope cases. The use of sensitive and selective detectors like the nigrogen-specific detector or a mass spectrometer is absolutely essential for routine work, as for non-specific detectors the number of \"false positives\" leads to an intolerable work load for the laboratory."}
{"id": "PMID:11867", "title": "Gonadal function in young adults after surgical treatment of cryptorchidism.", "content": "In a follow-up study of 48 young men who had been surgically treated for cryptorchidism before puberty testicular function was assessed by examining the genitalia, testicular volume, secondary sex characteristics, semen, plasma luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations after luteinising hormone-releasing hormone stimulation, and plasma testosterone concentrations. Clinical androgen effects were normal. The mean testicular volume of both testes was in the low normal range in those who had had unilateral cryptorchidism and below normal in those who had had bilateral cryptorchidism. Of 37 patients whose sperm counts were recorded (14 bilateral) six showed azoospermia (all bilateral), five had severe oligospermia (four bilateral), and 10 had moderate oligospermia (one bilateral). In nearly all those who had had bilateral cryptorchidism and most of those who had had unilateral cryptorchidism plasma gonadotrophin levels were increased. Four cases of possible partial LH deficiency were identified. Plasma testosterone concentrations were normal in all except two patients.", "contents": "Gonadal function in young adults after surgical treatment of cryptorchidism. In a follow-up study of 48 young men who had been surgically treated for cryptorchidism before puberty testicular function was assessed by examining the genitalia, testicular volume, secondary sex characteristics, semen, plasma luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations after luteinising hormone-releasing hormone stimulation, and plasma testosterone concentrations. Clinical androgen effects were normal. The mean testicular volume of both testes was in the low normal range in those who had had unilateral cryptorchidism and below normal in those who had had bilateral cryptorchidism. Of 37 patients whose sperm counts were recorded (14 bilateral) six showed azoospermia (all bilateral), five had severe oligospermia (four bilateral), and 10 had moderate oligospermia (one bilateral). In nearly all those who had had bilateral cryptorchidism and most of those who had had unilateral cryptorchidism plasma gonadotrophin levels were increased. Four cases of possible partial LH deficiency were identified. Plasma testosterone concentrations were normal in all except two patients."}
{"id": "PMID:11871", "title": "Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies.", "content": "Fifty-six brains from middle-aged and elderly normal as well as demented subjects and patients with provisional clinical diagnosis of other neurological and psychiatric diseases were assessed histologically. On this basis the specimens were classified into 14 diagnostic groups. A survey of potential indices of specific neurons has been carried out on these brains in which neurotransmitter-related enzymes, gamma-GTP (a potential index of capillaries) and specific proteins have been determined in up to 20 brain regions. In addition, the agonal state has been tentatively assessed by examining the post-mortem states of the circulatory and respiratory systems. CAT and gamma-GTP activities and the concentration of a soluble neuronal-type protein (neuronin S-5) were found to be relatively unaffected by the agonal state. When cases of senile dementia were compared to controls (matched with respect to the cause of death) the activity of CAT (the potential index of cholinergic neurons) appears to be reduced in the cerebral cortex. This is a preliminary finding, although a correlation was indicated between CAT activity and 'senile' morphological changes, the activity was markedly reduced in only 3 brains. However, despite inconsistencies in the literature (Karczmar, 1975) at least one pharmacological study on humans appears to show that the cholinergic system may be involved in age-related memory degeneration (Drachman and Leavitt, 1974). Cholinergic neurons may be abnormal in the other abiotrophies examined (Huntington's chorea, motor neuron disease and mixed vascular and senile dementia). gamma-GTP and neuronin S-5 (identical in most respects to the soluble acidic neuronal protein 14-3-2 of antigen alpha) were not reduced in senile dementia. The activities of brain decarboxylase (GAD and AAD) and the concentration of another soluble acidic brain protein (neuronin S-6) appear to be affected by the agonal state. This is remarkable because GAD and, in particular, neuronin S6, are relatively unaffected by post-mortem autolysis. As judged by the state of the extraneural systems which regulated the blood and oxygen supply to the brain it appears that terminal 'cerebral hypoxia' is responsible for the depletion of these brain constituents. This effect appears to be particularly marked in deep grey matter. In non-demented patients that die of bronchopneumonia, the areas of the cortex which are depleted in neuronin S-6 are consistent with the pattern of the 'selective vulnerability' of the cortex to hypoxia, suggesting that the terminal state can also affect the neocortex. If so, then this is particularly relevant to studies on senile dementia, for the effect of the terminal bronchopneumonia that so often occurs in these patients (and in patients with other abiotrophies) may be exacerbated by a terminal reduction in cerebral blood flow...", "contents": "Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Fifty-six brains from middle-aged and elderly normal as well as demented subjects and patients with provisional clinical diagnosis of other neurological and psychiatric diseases were assessed histologically. On this basis the specimens were classified into 14 diagnostic groups. A survey of potential indices of specific neurons has been carried out on these brains in which neurotransmitter-related enzymes, gamma-GTP (a potential index of capillaries) and specific proteins have been determined in up to 20 brain regions. In addition, the agonal state has been tentatively assessed by examining the post-mortem states of the circulatory and respiratory systems. CAT and gamma-GTP activities and the concentration of a soluble neuronal-type protein (neuronin S-5) were found to be relatively unaffected by the agonal state. When cases of senile dementia were compared to controls (matched with respect to the cause of death) the activity of CAT (the potential index of cholinergic neurons) appears to be reduced in the cerebral cortex. This is a preliminary finding, although a correlation was indicated between CAT activity and 'senile' morphological changes, the activity was markedly reduced in only 3 brains. However, despite inconsistencies in the literature (Karczmar, 1975) at least one pharmacological study on humans appears to show that the cholinergic system may be involved in age-related memory degeneration (Drachman and Leavitt, 1974). Cholinergic neurons may be abnormal in the other abiotrophies examined (Huntington's chorea, motor neuron disease and mixed vascular and senile dementia). gamma-GTP and neuronin S-5 (identical in most respects to the soluble acidic neuronal protein 14-3-2 of antigen alpha) were not reduced in senile dementia. The activities of brain decarboxylase (GAD and AAD) and the concentration of another soluble acidic brain protein (neuronin S-6) appear to be affected by the agonal state. This is remarkable because GAD and, in particular, neuronin S6, are relatively unaffected by post-mortem autolysis. As judged by the state of the extraneural systems which regulated the blood and oxygen supply to the brain it appears that terminal 'cerebral hypoxia' is responsible for the depletion of these brain constituents. This effect appears to be particularly marked in deep grey matter. In non-demented patients that die of bronchopneumonia, the areas of the cortex which are depleted in neuronin S-6 are consistent with the pattern of the 'selective vulnerability' of the cortex to hypoxia, suggesting that the terminal state can also affect the neocortex. If so, then this is particularly relevant to studies on senile dementia, for the effect of the terminal bronchopneumonia that so often occurs in these patients (and in patients with other abiotrophies) may be exacerbated by a terminal reduction in cerebral blood flow..."}
{"id": "PMID:11872", "title": "Development of neurotransmitter uptake in regions of the chick brain.", "content": "The uptake of postulated neurotransmitters of their precursors into regions of the developing chick brain and retina has been examined. The transport of low concentrations (around 10(-8) M) of GABA, glutamic acid, choline, dopamine and serotonin into homogenates was sodium and energy dependent and inhibited by a variety of pharmacological agents that are thought to act presynaptically. After morphological fractionation, the high affinity transport mechanism was concentrated in the nerve ending fraction. Compounds were poorly accumulated by the cerebral regions of the 6 day incubated chick embryo. After this time, the uptake capacity of each brain region studied exhibited a characteristic development profile. Mechanisms for GABA transport appeared early in development, while catecholamine and choline systems matured later. Homogenates of the cerebral hemispheres and optic lobes took up all compounds studied, while the retina and cerebellum of the young chick were able to take up only GABA to a significant extent.", "contents": "Development of neurotransmitter uptake in regions of the chick brain. The uptake of postulated neurotransmitters of their precursors into regions of the developing chick brain and retina has been examined. The transport of low concentrations (around 10(-8) M) of GABA, glutamic acid, choline, dopamine and serotonin into homogenates was sodium and energy dependent and inhibited by a variety of pharmacological agents that are thought to act presynaptically. After morphological fractionation, the high affinity transport mechanism was concentrated in the nerve ending fraction. Compounds were poorly accumulated by the cerebral regions of the 6 day incubated chick embryo. After this time, the uptake capacity of each brain region studied exhibited a characteristic development profile. Mechanisms for GABA transport appeared early in development, while catecholamine and choline systems matured later. Homogenates of the cerebral hemispheres and optic lobes took up all compounds studied, while the retina and cerebellum of the young chick were able to take up only GABA to a significant extent."}
{"id": "PMID:11873", "title": "Putative neurotransmitters of the avian visual pathway.", "content": "The ability of homogenates of the chick optic lobe to accumulate a series of possible neurotransmitters has been studied. High affinity uptake of several possible neurotransmitters was examined in optic lobes of 21-day-old embryos that had a single eye removed on the third day of incubation and in 23-day-old chicks that had an eye removed at hatch. Embryonic enucleation resulted in severe reduction of development of the ability of the contralateral optic lobe to take up tritiated GABA, dopamine, choline, serotonin and glutamate from solutions around 10(-8)M. Unilateral eye removal of new-hatched chicks caused failure of the denervated optic lobe to grow, but only the uptake capacity for glutamate was significantly recuced. This deficit was apparent as early as 4 days after enucleation. The transport of other compounds was unimpaired. The uptake of glutamate by homogenates of the optic tract was 43% of that or the optic lobe. This was a much greater fraction than the corresponding value for other postulated neurotransmitters. These data suggest that glutamate may be the primary neurotransmitter of the fibers of the optic tract originating in the retinal ganglion cells.", "contents": "Putative neurotransmitters of the avian visual pathway. The ability of homogenates of the chick optic lobe to accumulate a series of possible neurotransmitters has been studied. High affinity uptake of several possible neurotransmitters was examined in optic lobes of 21-day-old embryos that had a single eye removed on the third day of incubation and in 23-day-old chicks that had an eye removed at hatch. Embryonic enucleation resulted in severe reduction of development of the ability of the contralateral optic lobe to take up tritiated GABA, dopamine, choline, serotonin and glutamate from solutions around 10(-8)M. Unilateral eye removal of new-hatched chicks caused failure of the denervated optic lobe to grow, but only the uptake capacity for glutamate was significantly recuced. This deficit was apparent as early as 4 days after enucleation. The transport of other compounds was unimpaired. The uptake of glutamate by homogenates of the optic tract was 43% of that or the optic lobe. This was a much greater fraction than the corresponding value for other postulated neurotransmitters. These data suggest that glutamate may be the primary neurotransmitter of the fibers of the optic tract originating in the retinal ganglion cells."}
{"id": "PMID:11875", "title": "[Effect of sodium dichloroacetate on hyperlactatemia and hyperpyruvicemia induced by phenformin in the dog].", "content": "In the normal anesthetized dog a continuous perfusion of sodium dichloroacetate (30 mg/kg.h) prevents the increase in blood lactates and pyruvates as well as the lowering of the arterial pH induced by the intraduodenal administration of phenformin (30 mg/kg). Furthermore a perfusion of sodium dichloroacetate (7.5 mg/kg.mn) during 20 minutes, three hours after the administration of phenformin, tends to improve the utilization of blood lactates and pyruvates.", "contents": "[Effect of sodium dichloroacetate on hyperlactatemia and hyperpyruvicemia induced by phenformin in the dog]. In the normal anesthetized dog a continuous perfusion of sodium dichloroacetate (30 mg/kg.h) prevents the increase in blood lactates and pyruvates as well as the lowering of the arterial pH induced by the intraduodenal administration of phenformin (30 mg/kg). Furthermore a perfusion of sodium dichloroacetate (7.5 mg/kg.mn) during 20 minutes, three hours after the administration of phenformin, tends to improve the utilization of blood lactates and pyruvates."}
{"id": "PMID:11876", "title": "Alkaline phosphatase activity, characterization, and subcellular distribution during initial skeletogenesis in the prenatal rat limb.", "content": "The specific activity, tissue specificity, and subcellular distribution of alkaline phosphatase were studied in the fetal rat limb during initial cartilage calcification and bone formation. The pH optimum, Km, activation, and inhibition characteristics of the enzyme assayed for in 900 X g supernates of whole limb homogenates indicated that the activity represented a fetal bone alkaline phosphatase. Studies examining temporal changes of the enzyme in these preparations demonstrated a substantial increase in activity over each of the days during which they were studied (days 15-18). Fractions derived from the discontinuous density gradient centrifugation of the limb preparations were used to study the chronological subcellular distribution of the enzyme. Enzyme activity was found in all of the fractions with the greatest activity occurring in fractions consisting of ribosomes and small vesicles. The vesicular component was similar to the matrix vesicles dexcribed by others in calcifying tissues. The daily increase in activity measured in the curde supernate was further reflected in the distribution studies. The association of alkaline phosphatase with the vesicular structure is compatible with the theorized functions of matrix vesicles, and the substantial increase in activity between days 15 and 18 further demonstrates an intimate association of alkaline phosphatase with skeletal development.", "contents": "Alkaline phosphatase activity, characterization, and subcellular distribution during initial skeletogenesis in the prenatal rat limb. The specific activity, tissue specificity, and subcellular distribution of alkaline phosphatase were studied in the fetal rat limb during initial cartilage calcification and bone formation. The pH optimum, Km, activation, and inhibition characteristics of the enzyme assayed for in 900 X g supernates of whole limb homogenates indicated that the activity represented a fetal bone alkaline phosphatase. Studies examining temporal changes of the enzyme in these preparations demonstrated a substantial increase in activity over each of the days during which they were studied (days 15-18). Fractions derived from the discontinuous density gradient centrifugation of the limb preparations were used to study the chronological subcellular distribution of the enzyme. Enzyme activity was found in all of the fractions with the greatest activity occurring in fractions consisting of ribosomes and small vesicles. The vesicular component was similar to the matrix vesicles dexcribed by others in calcifying tissues. The daily increase in activity measured in the curde supernate was further reflected in the distribution studies. The association of alkaline phosphatase with the vesicular structure is compatible with the theorized functions of matrix vesicles, and the substantial increase in activity between days 15 and 18 further demonstrates an intimate association of alkaline phosphatase with skeletal development."}
{"id": "PMID:11877", "title": "The seeded growth of calcium phosphates. The kinetics of growth of dicalcium phosphate dihydrate on hydroxyapatite.", "content": "The kinetics of growth of calcium phosphate on synthetic HAP seed crystals has been studied at 37 degrees C and at pH values of 4.5 and 5.0 by the pH-stat controlled addition of base. Following an induction, DCPD crystal growth takes place with growth kinetics characteristic of the crystallization of pure DCPD seed. The effect of stirring rate, HAP seed concentration and initial degree of supersaturation with respect to DCPD on the kinetics of the growth process have been determined. The crystallization appears to be controlled by a surface reaction and nucleation of DCPD on the HAP substrate is completed in the initial induction period. Formation of DCPD under these conditions closely simulates plaque and calculus production in the mouth. Thus calculus that develops from the initial plaque is known to contain an appreciable amount of DCPD.", "contents": "The seeded growth of calcium phosphates. The kinetics of growth of dicalcium phosphate dihydrate on hydroxyapatite. The kinetics of growth of calcium phosphate on synthetic HAP seed crystals has been studied at 37 degrees C and at pH values of 4.5 and 5.0 by the pH-stat controlled addition of base. Following an induction, DCPD crystal growth takes place with growth kinetics characteristic of the crystallization of pure DCPD seed. The effect of stirring rate, HAP seed concentration and initial degree of supersaturation with respect to DCPD on the kinetics of the growth process have been determined. The crystallization appears to be controlled by a surface reaction and nucleation of DCPD on the HAP substrate is completed in the initial induction period. Formation of DCPD under these conditions closely simulates plaque and calculus production in the mouth. Thus calculus that develops from the initial plaque is known to contain an appreciable amount of DCPD."}
{"id": "PMID:11878", "title": "Pyrophosphatase and ATPase of isolated cartilage matrix vesicles.", "content": "Some of the characteristics of the pyrophosphatase and ATPase activities studied in isolated cartilage matrix vesicles were found to be similar to those already reported for the solubilized and purified bone alkaline phosphatase. Thus, the pH optimum of the pyrophosphatase activity responded similarly to changes in the concentration of Mg2+, Ca2+, and PPi. Further, the ATPase activity was not activated by Ca2+ in the presence of an optimal Mg2+ concentration. It is proposed that a function of the alkaline phosphatase of matrix vesicles in vivo is to hydrolyze the substrates PPi, ADP, and ATP, which are known inhibitors of calcium phosphate precipitation.", "contents": "Pyrophosphatase and ATPase of isolated cartilage matrix vesicles. Some of the characteristics of the pyrophosphatase and ATPase activities studied in isolated cartilage matrix vesicles were found to be similar to those already reported for the solubilized and purified bone alkaline phosphatase. Thus, the pH optimum of the pyrophosphatase activity responded similarly to changes in the concentration of Mg2+, Ca2+, and PPi. Further, the ATPase activity was not activated by Ca2+ in the presence of an optimal Mg2+ concentration. It is proposed that a function of the alkaline phosphatase of matrix vesicles in vivo is to hydrolyze the substrates PPi, ADP, and ATP, which are known inhibitors of calcium phosphate precipitation."}
{"id": "PMID:11879", "title": "The hydrolytic activity of L-ascorbic acid.", "content": "The ability of L-ascorbic acid to catalyze the liberation of 4-methylumbelliferone from 4-methylumbelliferyl-beta-D-N-acetylglucosaminide, 4-methylumbelliferyl-beta-D-glucuronide, 4-methylumbelliferyl-alpha-D-mannoside, and 4-methylumbelliferyl-beta-D-galactoside is documented. There is an apparent metal and oxygen dependency. The cleavage of two lipids was shown in addition to the hydrolysis of these fluorogenic glycosides. Galactose was liberated from galactosyl-6-[3H]ceramide and oleic acid from cholesterol-[1-14C]oleate by L-ascorbic acid under conditins usually used for in vitro incubations. In common with most in vitro systems, only a small percentage of substrate was degraded.", "contents": "The hydrolytic activity of L-ascorbic acid. The ability of L-ascorbic acid to catalyze the liberation of 4-methylumbelliferone from 4-methylumbelliferyl-beta-D-N-acetylglucosaminide, 4-methylumbelliferyl-beta-D-glucuronide, 4-methylumbelliferyl-alpha-D-mannoside, and 4-methylumbelliferyl-beta-D-galactoside is documented. There is an apparent metal and oxygen dependency. The cleavage of two lipids was shown in addition to the hydrolysis of these fluorogenic glycosides. Galactose was liberated from galactosyl-6-[3H]ceramide and oleic acid from cholesterol-[1-14C]oleate by L-ascorbic acid under conditins usually used for in vitro incubations. In common with most in vitro systems, only a small percentage of substrate was degraded."}
{"id": "PMID:11880", "title": "Adenosine triphosphate - dependent calcium binding and accumulation by guinea pig cardiac sarcolemma.", "content": "Sarcolemma isolated from guinea pig heart ventricles possessed ATP-dependent Ca2+ binding and accumulation (+ oxalate) activities which were not inhibited by sodium azide, oligomycin, or ruthenium red. Ca2+ binding and accumulation by sarcolemma were sensitive to pH, the optimum being about pH 6.8. The concentrations of ATP required for half-maximal binding and accumulation were 94.3 and 172 muM, respectively. Mg2+ up to 5 mM significantly enhanced both activities but was inhibitory at higher concentrations (greater than 10 mM). Sarcolemmal Ca2+ binding and accumulation were stimulated 100% by K+, half-maximal enhancement occurring at 5-10 mM K+. Ca2+ binding and accumulation were both saturable processes and the respective apparent Km values for Ca2+ were 16.4 and 14.3 muM. Ca2+ binding by sarcolemma was a rapid process and the bound Ca2+ was released upon depletion of ATP in the medium. It is suggested that the sarcolemmal Ca2+ transport system may well be of significance in regulation of the contraction-relaxation cycle of cardiac muscle.", "contents": "Adenosine triphosphate - dependent calcium binding and accumulation by guinea pig cardiac sarcolemma. Sarcolemma isolated from guinea pig heart ventricles possessed ATP-dependent Ca2+ binding and accumulation (+ oxalate) activities which were not inhibited by sodium azide, oligomycin, or ruthenium red. Ca2+ binding and accumulation by sarcolemma were sensitive to pH, the optimum being about pH 6.8. The concentrations of ATP required for half-maximal binding and accumulation were 94.3 and 172 muM, respectively. Mg2+ up to 5 mM significantly enhanced both activities but was inhibitory at higher concentrations (greater than 10 mM). Sarcolemmal Ca2+ binding and accumulation were stimulated 100% by K+, half-maximal enhancement occurring at 5-10 mM K+. Ca2+ binding and accumulation were both saturable processes and the respective apparent Km values for Ca2+ were 16.4 and 14.3 muM. Ca2+ binding by sarcolemma was a rapid process and the bound Ca2+ was released upon depletion of ATP in the medium. It is suggested that the sarcolemmal Ca2+ transport system may well be of significance in regulation of the contraction-relaxation cycle of cardiac muscle."}
{"id": "PMID:11881", "title": "Histone-histone interactions. II. Structural stability of the histone H3-H4 complex.", "content": "The stability of the histone H3-H4 complex toward urea, changes in pH and ionic strength, and certain chemical modifications have been examined by gel electrophoresis anc circular dichronism. When uncomplexed, the two cysteine residues of histone H3 become rapidly oxidized, forming an intramolecular disulfide bridge which apparently blocks complex formation on return to complexing conditions. The complex was found to be unstable toward low values of pH and ionic strength, concentrations of urea exceeding 1 M, modifications of the cysteine residues, and fragmention in which the C terminal portions of either H3 or H4 are removed. A possible structure for this complex is proposed.", "contents": "Histone-histone interactions. II. Structural stability of the histone H3-H4 complex. The stability of the histone H3-H4 complex toward urea, changes in pH and ionic strength, and certain chemical modifications have been examined by gel electrophoresis anc circular dichronism. When uncomplexed, the two cysteine residues of histone H3 become rapidly oxidized, forming an intramolecular disulfide bridge which apparently blocks complex formation on return to complexing conditions. The complex was found to be unstable toward low values of pH and ionic strength, concentrations of urea exceeding 1 M, modifications of the cysteine residues, and fragmention in which the C terminal portions of either H3 or H4 are removed. A possible structure for this complex is proposed."}
{"id": "PMID:11882", "title": "Circular dichroism studies of sheep beta-lipotropic hormone.", "content": "The far ultraviolet circular dichroism spectra of sheep beta-lipotropic hormone (beta-LPH) were recorded under different conditions of pH, temperature, salt concentration, and solvent composition. Results confirm the stability of the hormone in strong basic or acidic solutions; moreover, temperatures up to 50 degrees C do not seem to affect noticeably the conformation of beta-LPH. However, increasing the NaC1 concentration or addition of dioxane in the solution brings about a conformational transition of the chain, interpreted as an increase in the helical content. The method of Yang (Chen, Y.H., Yang, J. T. & Martinez, H. M. (1972) Biochemistry 11, 4120-4131) was used to compute the proportion of helical, beta, and unordered forms of the hormone chain. The proportions are compared with those obtained from Fasman's predictive method (Chou, P. Y & Fasman, G. D. (1974) Biochemistry 13, 211-221 and Chou, P. Y. & Fasman, G. D. (1974) Biochemistry 13, 222-245) based on the known amino acid sequence of beta-LPH.", "contents": "Circular dichroism studies of sheep beta-lipotropic hormone. The far ultraviolet circular dichroism spectra of sheep beta-lipotropic hormone (beta-LPH) were recorded under different conditions of pH, temperature, salt concentration, and solvent composition. Results confirm the stability of the hormone in strong basic or acidic solutions; moreover, temperatures up to 50 degrees C do not seem to affect noticeably the conformation of beta-LPH. However, increasing the NaC1 concentration or addition of dioxane in the solution brings about a conformational transition of the chain, interpreted as an increase in the helical content. The method of Yang (Chen, Y.H., Yang, J. T. & Martinez, H. M. (1972) Biochemistry 11, 4120-4131) was used to compute the proportion of helical, beta, and unordered forms of the hormone chain. The proportions are compared with those obtained from Fasman's predictive method (Chou, P. Y & Fasman, G. D. (1974) Biochemistry 13, 211-221 and Chou, P. Y. & Fasman, G. D. (1974) Biochemistry 13, 222-245) based on the known amino acid sequence of beta-LPH."}
{"id": "PMID:11883", "title": "The fusion of erythrocytes by treatment with proteolytic enzymes and polyethylene glycol.", "content": "Polyethylene glycol (PEG) has been utilized to induce homokaryocyte formation in avian and mammalian erythrocytes previously treated with proteolytic enzymes. PEG of molecular weight 6,000-7,5000 was found superior to 1,500 and 20,000 MW PEG. Cells exposed to protease alone, prior to PEG treatment, fused to a high degree (60-95% multinucleated cells), whereas trypsin or pepsin treatment alone allowed very little fusion (2.5%). Trypsin lowered the effectiveness of protease when used in combination. Cells which were not treated with proteolytic enzymes agglutinated in the presence of PEG but did not fuse to a significant extent (0.01%). Fusion was also markedly dependent upon the rate at which PEG was eluted during the fusion process. Electron microscopy indicated that fusion began during the elution of PEG from the agglutinated cells.", "contents": "The fusion of erythrocytes by treatment with proteolytic enzymes and polyethylene glycol. Polyethylene glycol (PEG) has been utilized to induce homokaryocyte formation in avian and mammalian erythrocytes previously treated with proteolytic enzymes. PEG of molecular weight 6,000-7,5000 was found superior to 1,500 and 20,000 MW PEG. Cells exposed to protease alone, prior to PEG treatment, fused to a high degree (60-95% multinucleated cells), whereas trypsin or pepsin treatment alone allowed very little fusion (2.5%). Trypsin lowered the effectiveness of protease when used in combination. Cells which were not treated with proteolytic enzymes agglutinated in the presence of PEG but did not fuse to a significant extent (0.01%). Fusion was also markedly dependent upon the rate at which PEG was eluted during the fusion process. Electron microscopy indicated that fusion began during the elution of PEG from the agglutinated cells."}
{"id": "PMID:11884", "title": "Congenital retroflexion of the penis and inguinal cryptorchidism in a presumptive bovine twin with a 60,XY/60,XX/61,XX,+cen chromosome constitution.", "content": "Studies were carried out on a yearling Holstein with external genitalia resembling those of a freemartin whose birth and developmental history was unknown. Dissection following slaughter showed testes close to the external inguinal rings, an underdeveloped penis coiled up subcutaneously in the perineum and terminating in a deep fossa at the level of the ischial arch and no evidence of a female genital tract. Chromosome analyses showed 60,XY cells in the blood and 60,XX and 61,XX,+cen cells in other tissues. It is postulated that the animal had a basic 60,XX/61,XX+cen mixoploid chromosome constitution, that the centric fragment functioned as a Y chromosome or as an autosomal modifier of the X chromosome in sex determination which accounted for the animal's Klinefelter syndrome-like abnormalities, and that animal was also twin to a bull which accounted for the presence of 60,XY cells in the blood.", "contents": "Congenital retroflexion of the penis and inguinal cryptorchidism in a presumptive bovine twin with a 60,XY/60,XX/61,XX,+cen chromosome constitution. Studies were carried out on a yearling Holstein with external genitalia resembling those of a freemartin whose birth and developmental history was unknown. Dissection following slaughter showed testes close to the external inguinal rings, an underdeveloped penis coiled up subcutaneously in the perineum and terminating in a deep fossa at the level of the ischial arch and no evidence of a female genital tract. Chromosome analyses showed 60,XY cells in the blood and 60,XX and 61,XX,+cen cells in other tissues. It is postulated that the animal had a basic 60,XX/61,XX+cen mixoploid chromosome constitution, that the centric fragment functioned as a Y chromosome or as an autosomal modifier of the X chromosome in sex determination which accounted for the animal's Klinefelter syndrome-like abnormalities, and that animal was also twin to a bull which accounted for the presence of 60,XY cells in the blood."}
{"id": "PMID:11886", "title": "Isoferritin composition of tissues and serum in human cancers.", "content": "A highly sensitive technique for isoferritin detection using 125I-labeled monospecific anti-human liver ferritin antibody for the identification of isoferritins after the analysis of small quantities of ferritin by isoelectric focusing in polyacryl-amide gels was applied to the study of renal, pancreatic, and colonic carcinomas. In all tumors studied, the isoferritin composition differed from that of the corresponding normal tissue; major isoferritins with pl more basic than those of the normal tissues were consistently detected. Composition of purified ferritin from metastases closely resembled the isoferritin composition of the primary tumors. Examination of the serum isoferritin profiles of four patients with cancers did not reveal the presence of any tumor-specific changes in isoferritins. It is suggested that the abnormality in tissue ferritins in the three human cancers studied is the synthesis of major isoferritins in the more basic range, rather than the appearance of tumor-specific isoferritins in the more acidic range.", "contents": "Isoferritin composition of tissues and serum in human cancers. A highly sensitive technique for isoferritin detection using 125I-labeled monospecific anti-human liver ferritin antibody for the identification of isoferritins after the analysis of small quantities of ferritin by isoelectric focusing in polyacryl-amide gels was applied to the study of renal, pancreatic, and colonic carcinomas. In all tumors studied, the isoferritin composition differed from that of the corresponding normal tissue; major isoferritins with pl more basic than those of the normal tissues were consistently detected. Composition of purified ferritin from metastases closely resembled the isoferritin composition of the primary tumors. Examination of the serum isoferritin profiles of four patients with cancers did not reveal the presence of any tumor-specific changes in isoferritins. It is suggested that the abnormality in tissue ferritins in the three human cancers studied is the synthesis of major isoferritins in the more basic range, rather than the appearance of tumor-specific isoferritins in the more acidic range."}
{"id": "PMID:11887", "title": "Increased guanylate cyclase activity and guanosine 3',5'-monophosphate content in ethionine-induced hepatomas.", "content": "Ethionine-induced hepatomas are characterized by high adenylate cyclase activity and cyclic adenosine 3',5'-monophosphate content relative to those of surrounding liver or liver from pair-fed control rats. The present study examined the properties of the guanylate cyclase-cyclic guanosine 3',5'-monophosphate (cGMP) system of these tissues. cGMP levels of the ethionine-induced hepatomas, determined in both specimens quick-forzen in situ and after in vitro incubation of tissue slices, were approximately 2 times higher than those of surrounding liver or controls. Higher cGMP in the tumors was associated with an increase in whole homogenate, soluble, and particulate guanylate cyclase activities, as well as an increase in soluble cGMP-phosphodiesterase activity. 3-Isobutyl-1-methylxanthine, a potent inhibitor of cGMP-phosphodiesterase activity, potentiated the differences in cGMP between slices of the hepatomas and surrounding liver or control, suggesting that the higher steady-state cGMP content of the tumors reflected enhanced basal cGMP synthesis which was partially offset by increased nucleotide degradation. In the hepatomas, a greater proportion of the total guanylate cyclase activity was located in the particulate cell fraction (31%) as compared to the subcellular distribution of enzyme activity in either surrounding liver or controls (15% of total in the particulate fraction). Carbamylcholine, which increased cGMP 3-fold in surrounding liver and controls, failed to alter cGMP levels inslices of hepatoma. Further, the relative changes in both cGMP accumulation and guanylate cyclase activity of the tumors in response to NaN3, NH2OH, and NaNO2 were blunted compared to surrounding liver or controls, although in each instance a response was clearly evident. Ethionine-induced hepatomas are thus characterized by: (a) significant increases in cGMP content and in guanylate cyclase and cGMP-phosphodiesterase activities, (b) a change in the subcellular distribution of guanylate cyclase, and (c) altered responsiveness of the guanylate cyclase-cGMP system to several agonists.", "contents": "Increased guanylate cyclase activity and guanosine 3',5'-monophosphate content in ethionine-induced hepatomas. Ethionine-induced hepatomas are characterized by high adenylate cyclase activity and cyclic adenosine 3',5'-monophosphate content relative to those of surrounding liver or liver from pair-fed control rats. The present study examined the properties of the guanylate cyclase-cyclic guanosine 3',5'-monophosphate (cGMP) system of these tissues. cGMP levels of the ethionine-induced hepatomas, determined in both specimens quick-forzen in situ and after in vitro incubation of tissue slices, were approximately 2 times higher than those of surrounding liver or controls. Higher cGMP in the tumors was associated with an increase in whole homogenate, soluble, and particulate guanylate cyclase activities, as well as an increase in soluble cGMP-phosphodiesterase activity. 3-Isobutyl-1-methylxanthine, a potent inhibitor of cGMP-phosphodiesterase activity, potentiated the differences in cGMP between slices of the hepatomas and surrounding liver or control, suggesting that the higher steady-state cGMP content of the tumors reflected enhanced basal cGMP synthesis which was partially offset by increased nucleotide degradation. In the hepatomas, a greater proportion of the total guanylate cyclase activity was located in the particulate cell fraction (31%) as compared to the subcellular distribution of enzyme activity in either surrounding liver or controls (15% of total in the particulate fraction). Carbamylcholine, which increased cGMP 3-fold in surrounding liver and controls, failed to alter cGMP levels inslices of hepatoma. Further, the relative changes in both cGMP accumulation and guanylate cyclase activity of the tumors in response to NaN3, NH2OH, and NaNO2 were blunted compared to surrounding liver or controls, although in each instance a response was clearly evident. Ethionine-induced hepatomas are thus characterized by: (a) significant increases in cGMP content and in guanylate cyclase and cGMP-phosphodiesterase activities, (b) a change in the subcellular distribution of guanylate cyclase, and (c) altered responsiveness of the guanylate cyclase-cGMP system to several agonists."}
{"id": "PMID:11888", "title": "Activation of guanylate cyclase by streptozotocin and 1-methyl-1-nitrosourea.", "content": "Streptozotocin has been shown to induce the production of a variety of tumors in rats. The present report demonstrates that streptozotocin and 1-methyl-1-nitrosourea, a component of the streptozotocin molecule and a known carcinogen, stimulate the enzyme guanylate cyclase which catalyzes the production of guanosine 3',5'-monophosphate. At a maximal concentration of 3 mg/ml, these agents activated guanylate cyclase approximately 30-fold in liver, 20-fold in kidney, 15-fold in cerebellum. 15- to 30-fold in cerebrum, 4- to 20-fold inheart, 12-fold in brain stem, 10-fold in lung, and 2-fold in pancreas. Since recent evidence suggests a role for guanosine 3',5'-monophosphate in malignant transformation, the data may help explain the tumor-inducing capacity of these agents.", "contents": "Activation of guanylate cyclase by streptozotocin and 1-methyl-1-nitrosourea. Streptozotocin has been shown to induce the production of a variety of tumors in rats. The present report demonstrates that streptozotocin and 1-methyl-1-nitrosourea, a component of the streptozotocin molecule and a known carcinogen, stimulate the enzyme guanylate cyclase which catalyzes the production of guanosine 3',5'-monophosphate. At a maximal concentration of 3 mg/ml, these agents activated guanylate cyclase approximately 30-fold in liver, 20-fold in kidney, 15-fold in cerebellum. 15- to 30-fold in cerebrum, 4- to 20-fold inheart, 12-fold in brain stem, 10-fold in lung, and 2-fold in pancreas. Since recent evidence suggests a role for guanosine 3',5'-monophosphate in malignant transformation, the data may help explain the tumor-inducing capacity of these agents."}
{"id": "PMID:11889", "title": "Use of an elemental diet in animals during treatment with 5-fluorouracil (NSC-19893).", "content": "Rats eating a diet containing casein hydrolysate (10% wt/wt)(diet 3) instead of whole casein (diet 1) exhibited increased tolerance to nine consecutive daily injections of 15 mg/kg of 5-fluorouracil (5-FU). The relative nutritional efficiency of diet 3 was significantly higher during 5-FU treatment. Serum albumin levels measured after 5-FU treatment dropped by only 2.7% in diet 3 groups and by 13.5% in diet 1 groups. Serum albumin values for rats on the control diet (Purina lab chow) were comparable to those on diet 1. No 5-FU-related mortality was observed in any of the groups. Intestinal brush border enzymes were determined in a group of rats on diet 1. At the end of 5-FU treatment statistically significant changes were observed: sucrase dropped to 30% of control and leucylnaphthylamide-hydrolyzing activity dropped to 19% of control. The activity of gamma-glutamyltransferase did not change significantly. It is postulated that under these circumstances a mixture with a prevalence of free amino acids (casein hydrolysate) could be more readily absorbed than a corresponding mixture containing a larger proportion of oligopeptides.", "contents": "Use of an elemental diet in animals during treatment with 5-fluorouracil (NSC-19893). Rats eating a diet containing casein hydrolysate (10% wt/wt)(diet 3) instead of whole casein (diet 1) exhibited increased tolerance to nine consecutive daily injections of 15 mg/kg of 5-fluorouracil (5-FU). The relative nutritional efficiency of diet 3 was significantly higher during 5-FU treatment. Serum albumin levels measured after 5-FU treatment dropped by only 2.7% in diet 3 groups and by 13.5% in diet 1 groups. Serum albumin values for rats on the control diet (Purina lab chow) were comparable to those on diet 1. No 5-FU-related mortality was observed in any of the groups. Intestinal brush border enzymes were determined in a group of rats on diet 1. At the end of 5-FU treatment statistically significant changes were observed: sucrase dropped to 30% of control and leucylnaphthylamide-hydrolyzing activity dropped to 19% of control. The activity of gamma-glutamyltransferase did not change significantly. It is postulated that under these circumstances a mixture with a prevalence of free amino acids (casein hydrolysate) could be more readily absorbed than a corresponding mixture containing a larger proportion of oligopeptides."}
{"id": "PMID:11893", "title": "[Daily variations of the level of neural secretions in Owenia fusiformis. Persistance of a daily rhythm in cultured tissues].", "content": "A quantitative study of elementary granules in neuron axons of the nervous chain of Owenia fusiformis (Annelid polychaete) shows that daily variations of the number of secretory granules occur in unamputated animals and in ventral tissue cultures. These variations are correlated with the thythm of the cell cycle.", "contents": "[Daily variations of the level of neural secretions in Owenia fusiformis. Persistance of a daily rhythm in cultured tissues]. A quantitative study of elementary granules in neuron axons of the nervous chain of Owenia fusiformis (Annelid polychaete) shows that daily variations of the number of secretory granules occur in unamputated animals and in ventral tissue cultures. These variations are correlated with the thythm of the cell cycle."}
{"id": "PMID:11894", "title": "[Demonstration of different metabolic pathways starting with glucose or fructose in Rhizobium meliloti].", "content": "Rhizobium meliloti can produce many polysaccharides on D-fructose and D-mannitol. In glucose-grown cultures, few polysaccharides are observed and 2 keto-gluconate is accumulated.", "contents": "[Demonstration of different metabolic pathways starting with glucose or fructose in Rhizobium meliloti]. Rhizobium meliloti can produce many polysaccharides on D-fructose and D-mannitol. In glucose-grown cultures, few polysaccharides are observed and 2 keto-gluconate is accumulated."}
{"id": "PMID:11895", "title": "[Enzymatic characteristics of the guanylate cyclase of KB cells: their change as a function of the development of the cultures].", "content": "We have localized 71% of the guanylate cyclase activity in the (G X 105,000) supernatent fraction of broken KB cells. The reaction follows Michaelis-Menten kinetics, the apparent Km for GTP is 0,5 mM, as long as GTP is lower than a limited concentration, then activity is inhibited. The ion Mn++ is an absolutely required activator, it does not change enzyme-substrate affinity. The enzyme shows several types of binding sites of Mn++. Guanylate cyclase, studied over a period of development of culture, shows, in KB cells without cell contact, an activity higher than that observed in confluent cells. This is not due to the fact of a change in enzyme-substrate affinity but to a modification of Mn++ influence.", "contents": "[Enzymatic characteristics of the guanylate cyclase of KB cells: their change as a function of the development of the cultures]. We have localized 71% of the guanylate cyclase activity in the (G X 105,000) supernatent fraction of broken KB cells. The reaction follows Michaelis-Menten kinetics, the apparent Km for GTP is 0,5 mM, as long as GTP is lower than a limited concentration, then activity is inhibited. The ion Mn++ is an absolutely required activator, it does not change enzyme-substrate affinity. The enzyme shows several types of binding sites of Mn++. Guanylate cyclase, studied over a period of development of culture, shows, in KB cells without cell contact, an activity higher than that observed in confluent cells. This is not due to the fact of a change in enzyme-substrate affinity but to a modification of Mn++ influence."}
{"id": "PMID:11896", "title": "Facial vein in the rabbit. Neurogenic vasodilation mediated by beta-adrenergic receptors.", "content": "A segment of the facial vein of the rabbit, that opposite the buccal cavity, responds to norepinephrine (NE) and opposite the buccal cavity, responds to norepinephrine (NE) and transmural nerve stimulation (TNS) by a brisk biphasic dilation. The dilation in response to both procedures is reveresed by prior exposure to propranolol (10(-6)M). Pretreatment with phenoxybenzamine (10(-5)M) increases the size of the neurogenic response and displaces the NE dose-relaxation curve to the left. Histamine causes a constrictor response exclusively. Sympathetic stimulation of a segment of the facial vein proximal to this buccal segment, and also of the external jugular vein, results in constriction. Light microscopy showed no fequtres which can account for the dilation, and fluorescence histochemistry using a modified Flack technique showed a dense adrenergic nerve plexus extending throughout the thickness of the media. We found that frequency-response characteristics and neuronal uptake of 3H-NE were consistent with findings for a blood vessel with a heavy medial innervation. Also, monoamine oxidase and catechol O-methyltransferase activities were similar to those found in other rabbit veins. Furthermore, these results are consistent with an adrenergic neuroeffector organization in which there is a predominance of beta- over alpha-adrenergic receptors. In conclusion, the presence of a dilator response in this buccal segment of the facial vein may be related to its location in the wall of the cheek, where it may be subjected to considerable stretch.", "contents": "Facial vein in the rabbit. Neurogenic vasodilation mediated by beta-adrenergic receptors. A segment of the facial vein of the rabbit, that opposite the buccal cavity, responds to norepinephrine (NE) and opposite the buccal cavity, responds to norepinephrine (NE) and transmural nerve stimulation (TNS) by a brisk biphasic dilation. The dilation in response to both procedures is reveresed by prior exposure to propranolol (10(-6)M). Pretreatment with phenoxybenzamine (10(-5)M) increases the size of the neurogenic response and displaces the NE dose-relaxation curve to the left. Histamine causes a constrictor response exclusively. Sympathetic stimulation of a segment of the facial vein proximal to this buccal segment, and also of the external jugular vein, results in constriction. Light microscopy showed no fequtres which can account for the dilation, and fluorescence histochemistry using a modified Flack technique showed a dense adrenergic nerve plexus extending throughout the thickness of the media. We found that frequency-response characteristics and neuronal uptake of 3H-NE were consistent with findings for a blood vessel with a heavy medial innervation. Also, monoamine oxidase and catechol O-methyltransferase activities were similar to those found in other rabbit veins. Furthermore, these results are consistent with an adrenergic neuroeffector organization in which there is a predominance of beta- over alpha-adrenergic receptors. In conclusion, the presence of a dilator response in this buccal segment of the facial vein may be related to its location in the wall of the cheek, where it may be subjected to considerable stretch."}
{"id": "PMID:11897", "title": "Diazotization of catecholamines and their analogs and metabolites for urinary screening tests: chemical aspects.", "content": "Coupling of diazotized p-nitroaniline to catecholamines and their metabolites in urine has been proposed for use in screening for secreting neuroblastoma in childhood. We have coupled diazotized p-nitroaniline to catecholamines, derivatives, and metabolites and examined the reaction products by thin-layer chromatography and physico-chemical methods (ultraviolet spectra, mass spectroscopy, nuclear magnetic resonance). We conclude that during diazotization, products containing a p-hydroxybenzyl alcohol or a p-hydroxybenzoic acid structure (e.g., vanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenyl-ethyleneglycol, metanephrine, normetanephrine, synephrine, and isoproterenol) react with a diazonium cation, with release of their alcohol or acid moiety. Therefore the mentioned qualitative screening methods are very nonspecific. In contrast, thin-layer chromatographic screening methods provide complete separation and unambiguous identification of those metabolites and are to be preferred for use in detecting secreting neuroblastoma in childhood.", "contents": "Diazotization of catecholamines and their analogs and metabolites for urinary screening tests: chemical aspects. Coupling of diazotized p-nitroaniline to catecholamines and their metabolites in urine has been proposed for use in screening for secreting neuroblastoma in childhood. We have coupled diazotized p-nitroaniline to catecholamines, derivatives, and metabolites and examined the reaction products by thin-layer chromatography and physico-chemical methods (ultraviolet spectra, mass spectroscopy, nuclear magnetic resonance). We conclude that during diazotization, products containing a p-hydroxybenzyl alcohol or a p-hydroxybenzoic acid structure (e.g., vanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenyl-ethyleneglycol, metanephrine, normetanephrine, synephrine, and isoproterenol) react with a diazonium cation, with release of their alcohol or acid moiety. Therefore the mentioned qualitative screening methods are very nonspecific. In contrast, thin-layer chromatographic screening methods provide complete separation and unambiguous identification of those metabolites and are to be preferred for use in detecting secreting neuroblastoma in childhood."}
{"id": "PMID:11898", "title": "A mechanism for the conversion of oxyhemoglobin to methemoglobin by nitrite.", "content": "Each mole of oxyhemoglobin iron converted to methemoglobin causes the oxidation of 1.5 mol of nitrite to nitrate and consumes 1 mol of protons. No oxygen is liberated. The overall reaction has two simultaneously occurring parts. In the beginning the rate-limiting reaction converting O2Hb to metHb is directly proportional to H+ and NO2- concentrations and is independent of metHb. The second portion accounts in major part for the stoichiometry and rate of the overall reaction. In this portion O2Hb tetramers and metHbNO2- are the reactants. Essentially no reaction takes place in the presence of CN-, which displaces nitrite from the metHbNO2-, nor in the presence of 0.5 mol/liter Nal, which converts the O2Hb to alphabeta-dimers. The autocatalytic nature of the overall reaction in the presence of excess nitrite is the result of metHb, which is formed in both parts of the reaction, associating with nitrite to increase the concentration of one reactant of the cyanide-sensitive part. The reaction rates at constant pH in excess nitrite are porportional to the product of the O2Hb concentration and the square of the metHb concentration. The rate increases up to about 66% conversion of O2Hb followed by a decrease as the O2Hb becomes limiting. The dissociation constant of metHbNO2- at 25 degrees C and pH = 6.4 was found to be 1.11+/-0.11 mmol/liter.", "contents": "A mechanism for the conversion of oxyhemoglobin to methemoglobin by nitrite. Each mole of oxyhemoglobin iron converted to methemoglobin causes the oxidation of 1.5 mol of nitrite to nitrate and consumes 1 mol of protons. No oxygen is liberated. The overall reaction has two simultaneously occurring parts. In the beginning the rate-limiting reaction converting O2Hb to metHb is directly proportional to H+ and NO2- concentrations and is independent of metHb. The second portion accounts in major part for the stoichiometry and rate of the overall reaction. In this portion O2Hb tetramers and metHbNO2- are the reactants. Essentially no reaction takes place in the presence of CN-, which displaces nitrite from the metHbNO2-, nor in the presence of 0.5 mol/liter Nal, which converts the O2Hb to alphabeta-dimers. The autocatalytic nature of the overall reaction in the presence of excess nitrite is the result of metHb, which is formed in both parts of the reaction, associating with nitrite to increase the concentration of one reactant of the cyanide-sensitive part. The reaction rates at constant pH in excess nitrite are porportional to the product of the O2Hb concentration and the square of the metHb concentration. The rate increases up to about 66% conversion of O2Hb followed by a decrease as the O2Hb becomes limiting. The dissociation constant of metHbNO2- at 25 degrees C and pH = 6.4 was found to be 1.11+/-0.11 mmol/liter."}
{"id": "PMID:11899", "title": "Relation of pH to fluorescence of serotonin, melatonin, and other indole compounds reacted with o-phthaldialdehyde.", "content": "We distinguished serotonin, malatonin, and other indole compounds by their markedly different fluorescence behavior when heated with o-phthaldialdehyde in different concentration of HCl, or after the subsequent addition of alkali. Fluorescence may increase, disappear, or change from blue to orange-red. Only melatonin developed significant fluorescence (at less than 0.5 mug/liter) when heated with the reagent in 50 mmol/liter HCl. Serotonin and 5-hydroxyindole compounds with a C-3 aliphatic chain lost their blue fluorescence when brought from strong to weakly acid and alkaline pH. Intense reddish fluorescence developed in strongly alkaline solution. C-5 methoxy derivatives, such as melatonin, maintained their blue fluorescence in alkaline solution. Differences in fluorescence color (and RF) also characterized these compounds on silica gel plates. The use of toluene decreased blank fluorescence, while sample preparation in dim light, as often recommended, resulted in diminished and less-stable fluorescence.", "contents": "Relation of pH to fluorescence of serotonin, melatonin, and other indole compounds reacted with o-phthaldialdehyde. We distinguished serotonin, malatonin, and other indole compounds by their markedly different fluorescence behavior when heated with o-phthaldialdehyde in different concentration of HCl, or after the subsequent addition of alkali. Fluorescence may increase, disappear, or change from blue to orange-red. Only melatonin developed significant fluorescence (at less than 0.5 mug/liter) when heated with the reagent in 50 mmol/liter HCl. Serotonin and 5-hydroxyindole compounds with a C-3 aliphatic chain lost their blue fluorescence when brought from strong to weakly acid and alkaline pH. Intense reddish fluorescence developed in strongly alkaline solution. C-5 methoxy derivatives, such as melatonin, maintained their blue fluorescence in alkaline solution. Differences in fluorescence color (and RF) also characterized these compounds on silica gel plates. The use of toluene decreased blank fluorescence, while sample preparation in dim light, as often recommended, resulted in diminished and less-stable fluorescence."}
{"id": "PMID:11900", "title": "An optimized continuous-monitoring procedure for semiautomated determination of serum acid phosphatase activity.", "content": "A continuous-monitoring method for measuring acid phosphatase activity with alpha-naphthyl phosphate as the substrate was critically evaluated and modified. Using partially purified prostatic acid phosphatase, we show that certain conditions for the assay must be satisfied to ensure linearity. These conditions include maintaining the pH between 5.6 and 5.9 and the addition of detergent to sustain linearity. The results obtained with alpha-naphthyl phosphate have been compared with those obtained by using p-nitrophenyl phosphate as substrate. When used with an automatic rate analyzer, the modified method is as sensitive but more reproducible.", "contents": "An optimized continuous-monitoring procedure for semiautomated determination of serum acid phosphatase activity. A continuous-monitoring method for measuring acid phosphatase activity with alpha-naphthyl phosphate as the substrate was critically evaluated and modified. Using partially purified prostatic acid phosphatase, we show that certain conditions for the assay must be satisfied to ensure linearity. These conditions include maintaining the pH between 5.6 and 5.9 and the addition of detergent to sustain linearity. The results obtained with alpha-naphthyl phosphate have been compared with those obtained by using p-nitrophenyl phosphate as substrate. When used with an automatic rate analyzer, the modified method is as sensitive but more reproducible."}
{"id": "PMID:11901", "title": "Enzymatic rate method for measuring cholesterol in serum.", "content": "An enzymatic rate assay is described for measuring cholesterol in serum. Cholesterol is analyzed by mixing 5 mul of sample with a reagent consisting of cholesterol esterase, cholesterol oxidase, catalase, acetylacetone, methanol, and hydroxypolyethoxydodecane in a ammonium  phosphate buffer at pH 7.0. The rate of increase in absorbance of the dihydrolutidine product is measured at 37 degrees C and 405 nm. The change in absorbance between 4 and 10 min is used to calculate the cholesterol concentrations by using simultaneously determined free cholesterol standards. The change is linearly related to cholesterol concentration up to 4 g/liter. Samples containing bilirubin up to 200 mg/liter, uric acid up to 200 mg/liter, and hemoglobin up to 1 g/liter, or certain drugs (clofibrate, phenobarbital, nicotinic acid, salicylate, Ketochol, and Ovral) gave no interference. Ascorbic acid added to serum caused a positive interference. Lipemic samples gave values that were slightly lower than did the method of Abell et al., used for comparison. Our kinetic assay, compared with the method of Abell et al., the enzymatic assay used with Abbott's Bichromatic Analyzer, and the Technicon SMA 12/60 enzymatic procedure gave correlation coefficients of 0.992, 0.985, and 0.986, respectively.", "contents": "Enzymatic rate method for measuring cholesterol in serum. An enzymatic rate assay is described for measuring cholesterol in serum. Cholesterol is analyzed by mixing 5 mul of sample with a reagent consisting of cholesterol esterase, cholesterol oxidase, catalase, acetylacetone, methanol, and hydroxypolyethoxydodecane in a ammonium  phosphate buffer at pH 7.0. The rate of increase in absorbance of the dihydrolutidine product is measured at 37 degrees C and 405 nm. The change in absorbance between 4 and 10 min is used to calculate the cholesterol concentrations by using simultaneously determined free cholesterol standards. The change is linearly related to cholesterol concentration up to 4 g/liter. Samples containing bilirubin up to 200 mg/liter, uric acid up to 200 mg/liter, and hemoglobin up to 1 g/liter, or certain drugs (clofibrate, phenobarbital, nicotinic acid, salicylate, Ketochol, and Ovral) gave no interference. Ascorbic acid added to serum caused a positive interference. Lipemic samples gave values that were slightly lower than did the method of Abell et al., used for comparison. Our kinetic assay, compared with the method of Abell et al., the enzymatic assay used with Abbott's Bichromatic Analyzer, and the Technicon SMA 12/60 enzymatic procedure gave correlation coefficients of 0.992, 0.985, and 0.986, respectively."}
{"id": "PMID:11905", "title": "Erythrocyte glutathione synthetase in 5-oxoprolinuria: kinetic studies of the mutant enzyme and detection of heterozygotes.", "content": "The primary metabolic defect in 5-oxoprolinuria is a generalized deficiency of glutathione synthetase. The activity of this enzyme was determined in cell-free extracts of erythrocytes from patients with 5-oxoprolinuria, their parents and a sibling as well as from normal control individuals. The following activities (pkat/mg of hemoglobin) for glutathione synthetase were obtained: homozygotes mean 0.10 (range 0.07-0.12), heterozygotes mean 3.1 (range 2.8-3.7) and control individuals mean 6.1 (range 5.4-6.7). These results indicate that 5-oxoprolinuria, i.e. the defective gluthione synthetase gene(s), is transmitted by autosomal recessive inheritance. Studies of the kinetics of the low remaining activity of erythrocyte glutathione synthetase in patients with 5-oxoprolinuria failed to reveal defective affinity for glycine, gamma-glutamyl-alpha-aminobutyrate, ATP and Mg2+ ions. Furthermore, the pH optimum, time curves and temperature dependence for the mutant enzyme activity did not significantly differ from the corresponding parameters observed with normal enzyme.", "contents": "Erythrocyte glutathione synthetase in 5-oxoprolinuria: kinetic studies of the mutant enzyme and detection of heterozygotes. The primary metabolic defect in 5-oxoprolinuria is a generalized deficiency of glutathione synthetase. The activity of this enzyme was determined in cell-free extracts of erythrocytes from patients with 5-oxoprolinuria, their parents and a sibling as well as from normal control individuals. The following activities (pkat/mg of hemoglobin) for glutathione synthetase were obtained: homozygotes mean 0.10 (range 0.07-0.12), heterozygotes mean 3.1 (range 2.8-3.7) and control individuals mean 6.1 (range 5.4-6.7). These results indicate that 5-oxoprolinuria, i.e. the defective gluthione synthetase gene(s), is transmitted by autosomal recessive inheritance. Studies of the kinetics of the low remaining activity of erythrocyte glutathione synthetase in patients with 5-oxoprolinuria failed to reveal defective affinity for glycine, gamma-glutamyl-alpha-aminobutyrate, ATP and Mg2+ ions. Furthermore, the pH optimum, time curves and temperature dependence for the mutant enzyme activity did not significantly differ from the corresponding parameters observed with normal enzyme."}
{"id": "PMID:11906", "title": "A microfluorometric assay of leukocyte alpha-1,4-glucosidase.", "content": "We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease). The procedure requires smaller volumes of blood and less time than previous methods. The assay involves the separation of leukocytes by Peter's method for beta-glucosidase and a modification of Salafsky and Nadler's fluorometric method for alpha-glucosidase.", "contents": "A microfluorometric assay of leukocyte alpha-1,4-glucosidase. We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease). The procedure requires smaller volumes of blood and less time than previous methods. The assay involves the separation of leukocytes by Peter's method for beta-glucosidase and a modification of Salafsky and Nadler's fluorometric method for alpha-glucosidase."}
{"id": "PMID:11907", "title": "Studies on gamma-glutamyl transpeptidase of human urine.", "content": "A simple and rapid method suitable for clinical laboratories, for the removal of the inhibitors in urine of gamma-glutamyl transpeptidase activity, using an ion-retardation resin, is described. Gel chromatography of urine resulted in appreciable loss of the enzyme activity. Freezing at -5 degrees C and thawing, did not affect the activity of the enzyme. Dimethyl sulfoxide and polyvinyl pyrrolidone up to a creatinine and NaCl at levels found in normal urine did not inhibit the transpeptidase.", "contents": "Studies on gamma-glutamyl transpeptidase of human urine. A simple and rapid method suitable for clinical laboratories, for the removal of the inhibitors in urine of gamma-glutamyl transpeptidase activity, using an ion-retardation resin, is described. Gel chromatography of urine resulted in appreciable loss of the enzyme activity. Freezing at -5 degrees C and thawing, did not affect the activity of the enzyme. Dimethyl sulfoxide and polyvinyl pyrrolidone up to a creatinine and NaCl at levels found in normal urine did not inhibit the transpeptidase."}
{"id": "PMID:11908", "title": "Studies on the multiple forms of gamma-glutamyltransferase.", "content": "In sera of 53 patients with highly raised gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) activity, the gamma-GT was separated by column chromatography on Sephadex DEAE A-50 into two fractions. In 35 sera only one gamma-GT fraction was found at a conductivity of 2.0--2.5 mS and in 18 sera two gamma-GT fractions were found at a conductivity of 0.2 mS and again at 2.0--2.5 mS. There was no opvious correlation to the underlying disease. In 20 sera the additional parameters, protein, protein electrophoresis, free and esterified cholesterol, bilirubin, triglycerides, lipoprotein pattern and lipoprotein X were examined. We recognized, that the two forms of the gamma-GT are not true isoenzymes but that the separation of the gamma-GT into two fractions is caused by a different distribution of the cholesterol containing lipoprotei,s.", "contents": "Studies on the multiple forms of gamma-glutamyltransferase. In sera of 53 patients with highly raised gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) activity, the gamma-GT was separated by column chromatography on Sephadex DEAE A-50 into two fractions. In 35 sera only one gamma-GT fraction was found at a conductivity of 2.0--2.5 mS and in 18 sera two gamma-GT fractions were found at a conductivity of 0.2 mS and again at 2.0--2.5 mS. There was no opvious correlation to the underlying disease. In 20 sera the additional parameters, protein, protein electrophoresis, free and esterified cholesterol, bilirubin, triglycerides, lipoprotein pattern and lipoprotein X were examined. We recognized, that the two forms of the gamma-GT are not true isoenzymes but that the separation of the gamma-GT into two fractions is caused by a different distribution of the cholesterol containing lipoprotei,s."}
{"id": "PMID:11910", "title": "Human leucocyte alpha-L-fucosidase.", "content": "1. Human alpha-L-fucosidase (EC 3.2.1.51) was studied from leucocytes, urine and serum. 2. The leucocyte and urine enzymes are similar in many properties (KM, pH optimum, electrophoretic pattern, heat stability). 3. The serum alpha-L-fucosidase differs from the leucocyte and 4rine enzyme wit,respect to: electrophoretic pattern, pH optimum and heat stapility. 4. The molecular weight of leucocyte alpha-L-fucosidase was determined to be 80 000 +/- 5000. 5. Cu2+, Hg2+ and PCMB are strong inhibitors of leucocyte alpha-L-fucosidase. This inhibition could be completely reversed by beta-mercaptoethanol, indicating that thiol groups are essential for catalytic activity.", "contents": "Human leucocyte alpha-L-fucosidase. 1. Human alpha-L-fucosidase (EC 3.2.1.51) was studied from leucocytes, urine and serum. 2. The leucocyte and urine enzymes are similar in many properties (KM, pH optimum, electrophoretic pattern, heat stability). 3. The serum alpha-L-fucosidase differs from the leucocyte and 4rine enzyme wit,respect to: electrophoretic pattern, pH optimum and heat stapility. 4. The molecular weight of leucocyte alpha-L-fucosidase was determined to be 80 000 +/- 5000. 5. Cu2+, Hg2+ and PCMB are strong inhibitors of leucocyte alpha-L-fucosidase. This inhibition could be completely reversed by beta-mercaptoethanol, indicating that thiol groups are essential for catalytic activity."}
{"id": "PMID:11911", "title": "Characterization of alpha-L-fucosidase from two different families with fucosidosis.", "content": "1. Two different families with a different type of fucosidase deficiency are described. 2. In the first family the activity of alpha-L-fucosidase in leucocytes of two patients with fucosidosis type I was about 4 to 8% of the normal value. The activity of alpha-L-fucosidase in the leucocytes of the father and the mother are in the heterozygote range, while a sister of the propositus showed normal values. 3. The activity of alpha-L-fucosidase of the propositus from urine, serum and liver were also severely decreased. The activity of alpha-L-fucosidase in the urine of the parents and the healthy sister of thr propositus were about 5% of the mean normal value. However in the serum these values were above 50%. 4. The KM value for alpha-L-fucosidase from leucocytes of the patient was increased about 10 times and in serum this value was even higher. The KM values from the enzyme of the parents were in the normal range. 5. The abnormal enzyme from the propositus is unique in its thermal behaviour since after heating its activity increased. 6. In the second fanily the activity of alpha-L-fucosidase in the leucocytes of the patient is about 30% of the mean normal value, while the arylsulphatase A activity is also decreased (25% of the mean normal value). 7. The activity of alpha-L-fucosidase from the leucocytes of the father and the healthy brother are about 50% of the mean normal level, while the enzyme of the mother showed a normal activity. 8. The alpha-L-fucosidase activity in the urine and the liver of the propositus is also decreased. The serum enzyme activity however was in the normal range. 9. The KM value of alpha-L-fucosidase and heat stability of the enzyme of the patient were normal. In the leectrophoretic pattern of the whole family one bond was missing.", "contents": "Characterization of alpha-L-fucosidase from two different families with fucosidosis. 1. Two different families with a different type of fucosidase deficiency are described. 2. In the first family the activity of alpha-L-fucosidase in leucocytes of two patients with fucosidosis type I was about 4 to 8% of the normal value. The activity of alpha-L-fucosidase in the leucocytes of the father and the mother are in the heterozygote range, while a sister of the propositus showed normal values. 3. The activity of alpha-L-fucosidase of the propositus from urine, serum and liver were also severely decreased. The activity of alpha-L-fucosidase in the urine of the parents and the healthy sister of thr propositus were about 5% of the mean normal value. However in the serum these values were above 50%. 4. The KM value for alpha-L-fucosidase from leucocytes of the patient was increased about 10 times and in serum this value was even higher. The KM values from the enzyme of the parents were in the normal range. 5. The abnormal enzyme from the propositus is unique in its thermal behaviour since after heating its activity increased. 6. In the second fanily the activity of alpha-L-fucosidase in the leucocytes of the patient is about 30% of the mean normal value, while the arylsulphatase A activity is also decreased (25% of the mean normal value). 7. The activity of alpha-L-fucosidase from the leucocytes of the father and the healthy brother are about 50% of the mean normal level, while the enzyme of the mother showed a normal activity. 8. The alpha-L-fucosidase activity in the urine and the liver of the propositus is also decreased. The serum enzyme activity however was in the normal range. 9. The KM value of alpha-L-fucosidase and heat stability of the enzyme of the patient were normal. In the leectrophoretic pattern of the whole family one bond was missing."}
{"id": "PMID:11913", "title": "Rapid colorimetric assay of beta-galactosidase and N-acetyl-beta-glucosaminidase in human urine.", "content": "Colorimetric methods using 4-nitrophenyl-glycoside substrates for the assay of beta-galactosidase and N-acetyl-beta-glucosaminidase in human urine are described. Interfering substances were removed by gel-filtration of urine. An unidentified low-molecular-weight inhibitor of N-acetyl-beta-glucosaminidase was found. Increased sensitivity of the methods was achieved by high sample volumes, small volumes of buffer to terminate the enzyme reaction and optimal substrate concentration and buffer pH. Incubation periods were shortened to 15 min. Both methods were designed as single-tube tests in which buffer-substrate solutions are prepared in bulk and aliquots are stored in individual containers at -25 degrees C. Under these conditions reagents were stable for at least six months. Precision of both methods was satisfactory. Estimates of normal limits are reported.", "contents": "Rapid colorimetric assay of beta-galactosidase and N-acetyl-beta-glucosaminidase in human urine. Colorimetric methods using 4-nitrophenyl-glycoside substrates for the assay of beta-galactosidase and N-acetyl-beta-glucosaminidase in human urine are described. Interfering substances were removed by gel-filtration of urine. An unidentified low-molecular-weight inhibitor of N-acetyl-beta-glucosaminidase was found. Increased sensitivity of the methods was achieved by high sample volumes, small volumes of buffer to terminate the enzyme reaction and optimal substrate concentration and buffer pH. Incubation periods were shortened to 15 min. Both methods were designed as single-tube tests in which buffer-substrate solutions are prepared in bulk and aliquots are stored in individual containers at -25 degrees C. Under these conditions reagents were stable for at least six months. Precision of both methods was satisfactory. Estimates of normal limits are reported."}
{"id": "PMID:11914", "title": "Comparative studies on cholesterol oxidases from different sources.", "content": "1. Comparison of the characteristics of cholesterol oxidases from different sources was made by a new polarographic method for measurement of the oxygen-consumption rate. 2. A pH optimum of 7.0 was observed for cholesterol oxidases isolated from Nocardia and Brevibacterium, pH 5.0 for the enzyme from Schizophyllum and pH 7.5 for the enzyme from Streptomyces. 3. In the system used in the present study, Ca2+ and Mg2+ had no effect on these enzyme activities. On the other hand, the Schizophyllum enzyme was strongly inhibited by increasing concentrations of Cu2+, whereas the brevibacterium enzyme was slightly activated by them and Nocardia and Streptomyces enzymes were not affected. Hg2+ strongly inhibited the activities of enzymes the Schizophyllum enzyme. 4. Using serum as substrate, the cholesterol oxidases employed, except for the enzyme from Streptomyces, were not active without detergent in the reaction mixture. Effects of various detergents at various concentrations on the enzyme activities were studied. 5. Results of studies on the reaction of cholesterol oxidases on free cholesterol in low-and high-density lipoproteins were also compared.", "contents": "Comparative studies on cholesterol oxidases from different sources. 1. Comparison of the characteristics of cholesterol oxidases from different sources was made by a new polarographic method for measurement of the oxygen-consumption rate. 2. A pH optimum of 7.0 was observed for cholesterol oxidases isolated from Nocardia and Brevibacterium, pH 5.0 for the enzyme from Schizophyllum and pH 7.5 for the enzyme from Streptomyces. 3. In the system used in the present study, Ca2+ and Mg2+ had no effect on these enzyme activities. On the other hand, the Schizophyllum enzyme was strongly inhibited by increasing concentrations of Cu2+, whereas the brevibacterium enzyme was slightly activated by them and Nocardia and Streptomyces enzymes were not affected. Hg2+ strongly inhibited the activities of enzymes the Schizophyllum enzyme. 4. Using serum as substrate, the cholesterol oxidases employed, except for the enzyme from Streptomyces, were not active without detergent in the reaction mixture. Effects of various detergents at various concentrations on the enzyme activities were studied. 5. Results of studies on the reaction of cholesterol oxidases on free cholesterol in low-and high-density lipoproteins were also compared."}
{"id": "PMID:11915", "title": "Catecholamine-sensitive adenylate cyclase of human fat cell ghosts. Characteristics of the GMP(PNP)-liganded state.", "content": "The effects of 5'-guanylyl-imidodiphosphate (GMP(PNP)) on the catecholamine-sensitive adenylate cyclase of human fat cell ghosts were studied. The compound increased basal and epinephrine-stimulated enzyme activity by about 300%; in addition GMP(PNP) increased hormone sensitivity by reducing the epinephrine concentration required, to produce half maximal stimulation. The rate of GMP(PNP)-induced activation was slow in onset and could be enhanced by epinephrine. The GMP(PNP)-activated state was resistant to thermal inactivation and could not be reversed by extensive washing. The application of this compound in clinical studies may be useful because of its stimulating and stabilizing action.", "contents": "Catecholamine-sensitive adenylate cyclase of human fat cell ghosts. Characteristics of the GMP(PNP)-liganded state. The effects of 5'-guanylyl-imidodiphosphate (GMP(PNP)) on the catecholamine-sensitive adenylate cyclase of human fat cell ghosts were studied. The compound increased basal and epinephrine-stimulated enzyme activity by about 300%; in addition GMP(PNP) increased hormone sensitivity by reducing the epinephrine concentration required, to produce half maximal stimulation. The rate of GMP(PNP)-induced activation was slow in onset and could be enhanced by epinephrine. The GMP(PNP)-activated state was resistant to thermal inactivation and could not be reversed by extensive washing. The application of this compound in clinical studies may be useful because of its stimulating and stabilizing action."}
{"id": "PMID:11916", "title": "Galactose-1-phosphate uridyltransferase in cultured cells.", "content": "A method to measure the enzyme galactose-1-phosphate uridyltransferase in cultured cells is described. The optimun pH was 8.7 and no enzyme activity was found without preincubation with dithiothreitol. The KM values for Gal-1-P and UDPG for the wild type enzyme were found to be 0.2 mM and 0.08 mM, respectively. Values for the Duarte variant were found to be identical. No significant change in enzyme activity with time after subculture was found in either cultured skin fibroblasts or cultured amniotic fluid cells. Different transferase genotypes were clearly distinguished and reference range established. Transferase levels found in normal cultured amniotic fluid cells were the same as in normal cultured skin fibroblasts. The results of a prenatal diagnosis was obtained within 3 weeks of amniocentesis.", "contents": "Galactose-1-phosphate uridyltransferase in cultured cells. A method to measure the enzyme galactose-1-phosphate uridyltransferase in cultured cells is described. The optimun pH was 8.7 and no enzyme activity was found without preincubation with dithiothreitol. The KM values for Gal-1-P and UDPG for the wild type enzyme were found to be 0.2 mM and 0.08 mM, respectively. Values for the Duarte variant were found to be identical. No significant change in enzyme activity with time after subculture was found in either cultured skin fibroblasts or cultured amniotic fluid cells. Different transferase genotypes were clearly distinguished and reference range established. Transferase levels found in normal cultured amniotic fluid cells were the same as in normal cultured skin fibroblasts. The results of a prenatal diagnosis was obtained within 3 weeks of amniocentesis."}
{"id": "PMID:11959", "title": "Herbicides and soil microorganisms.", "content": "The production and usage of herbicides have increased dramatically in recent years. Consequently there is growing concern about the effects of these chemicals on the environment, particularly the possible long-term effects on soil fertility which may result from disturbance of the soil microflora. This review considers the recent developments in the study of the interactions between herbicides and microorganisms, and discusses the problems of evaluating the results of such studies with a view to determining or predicting possible short-term or long-term effects which may be of practical significance.", "contents": "Herbicides and soil microorganisms. The production and usage of herbicides have increased dramatically in recent years. Consequently there is growing concern about the effects of these chemicals on the environment, particularly the possible long-term effects on soil fertility which may result from disturbance of the soil microflora. This review considers the recent developments in the study of the interactions between herbicides and microorganisms, and discusses the problems of evaluating the results of such studies with a view to determining or predicting possible short-term or long-term effects which may be of practical significance."}
{"id": "PMID:11960", "title": "Evaluation of anxiolytic and amnesic effects of intramuscular lorazepam as a pre-operative medication.", "content": "In a double-blind investigation in 21 patients undergoing minor plastic surgery the effects of 4 mg lorazepam or a mixture of 20 mg papaveretum/400 mug hyoscine given intramuscularly as premedicants were studied. Lorazepam produced superior preoperative and post-operative anterograde amnesia, with respect to both incidence and duration. There was no difference in the pre-operative anxiolytic and soporofic effects of the two regimens and post-operatively, analgesic requirements and the incidence of vomitting and restlessness were the same in both groups of patients.", "contents": "Evaluation of anxiolytic and amnesic effects of intramuscular lorazepam as a pre-operative medication. In a double-blind investigation in 21 patients undergoing minor plastic surgery the effects of 4 mg lorazepam or a mixture of 20 mg papaveretum/400 mug hyoscine given intramuscularly as premedicants were studied. Lorazepam produced superior preoperative and post-operative anterograde amnesia, with respect to both incidence and duration. There was no difference in the pre-operative anxiolytic and soporofic effects of the two regimens and post-operatively, analgesic requirements and the incidence of vomitting and restlessness were the same in both groups of patients."}
{"id": "PMID:11961", "title": "Lorazepam in the treatment of neurosis.", "content": "An open study was carried out in 40 ambulatory neurotic patients with classical symptoms of anxiety to assess which of their symptoms responded most readily and favourably to treatment with lorazepam. Doses ranged from 2 mg to 15 mg daily and were adjusted to individual patient needs. The study period lasted 4 weeks and patients' individual symptoms were assessed weekly on a 4-point severity rating scale. The results showed a statistically significant and marked improvement during the first week for the majority of the 16 symptoms assessed, particularly emotional tension, irritability and apprehension. Symptoms with a cognitive element of anxiety were controlled to a lesser extent and were slower to respond. The few side-effects which were reported, mainly somnolence, appeared to be dose related and usually occurred during the first few days of treatment.", "contents": "Lorazepam in the treatment of neurosis. An open study was carried out in 40 ambulatory neurotic patients with classical symptoms of anxiety to assess which of their symptoms responded most readily and favourably to treatment with lorazepam. Doses ranged from 2 mg to 15 mg daily and were adjusted to individual patient needs. The study period lasted 4 weeks and patients' individual symptoms were assessed weekly on a 4-point severity rating scale. The results showed a statistically significant and marked improvement during the first week for the majority of the 16 symptoms assessed, particularly emotional tension, irritability and apprehension. Symptoms with a cognitive element of anxiety were controlled to a lesser extent and were slower to respond. The few side-effects which were reported, mainly somnolence, appeared to be dose related and usually occurred during the first few days of treatment."}
{"id": "PMID:11963", "title": "The role of HCO3-stimulated ATPase in buffer transport.", "content": "An ATPase stimulated by HCO-3ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO-3ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO-3. The HCO-3ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'nucleotidase. The activities of the HCO-3ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO-3 and K+ ions by the rat salivary duct epithelium. In renal cortex tissue, where HCO-3 is actively reabsorbed respectively H+ is secreted, there was also found a parallel change in the activity of the HCO-3ATPase and the rate of active H+ secretion. These findings provide further evidence that the membrane-bound HCO-3ATPase is involved in active H+/HCO-3 transport. The HCO-3ATPase is not only stimulated by HCO-3 but also by other non transportable oxybases, a finding which indicates H+ rather than HCO-3 being the actively transported component of the buffer system. Small concentrations of K+ ions decrease the Km for HCO-3 and thus yield stimulation of the HCO-3-ATPase. Thport changing in parallel with that of H+/HCO-3 may be taken as indicative for a coupled K+-H+-exchange mechanism to which the HCO-3ATPase is linked.", "contents": "The role of HCO3-stimulated ATPase in buffer transport. An ATPase stimulated by HCO-3ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO-3ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO-3. The HCO-3ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'nucleotidase. The activities of the HCO-3ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO-3 and K+ ions by the rat salivary duct epithelium. In renal cortex tissue, where HCO-3 is actively reabsorbed respectively H+ is secreted, there was also found a parallel change in the activity of the HCO-3ATPase and the rate of active H+ secretion. These findings provide further evidence that the membrane-bound HCO-3ATPase is involved in active H+/HCO-3 transport. The HCO-3ATPase is not only stimulated by HCO-3 but also by other non transportable oxybases, a finding which indicates H+ rather than HCO-3 being the actively transported component of the buffer system. Small concentrations of K+ ions decrease the Km for HCO-3 and thus yield stimulation of the HCO-3-ATPase. Thport changing in parallel with that of H+/HCO-3 may be taken as indicative for a coupled K+-H+-exchange mechanism to which the HCO-3ATPase is linked."}
{"id": "PMID:11964", "title": "Polarity of proximal tubular epithelial cells in relation to transepithelial transport.", "content": "Transport properties of brush border microvilli and basal-lateral plasma membranes isolated from rat kidney cortex were studied by a millipore filtration technique. Brush border microvilli but not basal-lateral plasma membranes contain sodium dependent stereospecific transport system for D-glucose, L-phenylalanine and inorganic phosphate as indicated by saturability, countertransport and inhibition by structurally related compounds. Reduction of equilbrium uptake by increasing medium osmolarity suggests transport into an osmotically reactive space rather than binding to the membranes. Electrogenecity of the sodium-sugar and sodium-amino-acid cotransport system was established by their dependence on artificially imposed diffusion potentials. Also a NA+/H+ antiport system can be demonstrated in microvilli vesicles by demonstrating counterflow of both ions under short circuit conditions. Basal-lateral plasma membranes contain sodium independent stereospecific transport systems for sugars and amino acids. These results demonstrate a marked functional polarity of the cell membranes in respect to sodium dependent and sodium independent transport systems. This polarity in conjunction with the asymmetrical distribution of sodium between the intra- and extracellular space seems to enable the proximal tubule epithelial cells to perform active transepithelial transport.", "contents": "Polarity of proximal tubular epithelial cells in relation to transepithelial transport. Transport properties of brush border microvilli and basal-lateral plasma membranes isolated from rat kidney cortex were studied by a millipore filtration technique. Brush border microvilli but not basal-lateral plasma membranes contain sodium dependent stereospecific transport system for D-glucose, L-phenylalanine and inorganic phosphate as indicated by saturability, countertransport and inhibition by structurally related compounds. Reduction of equilbrium uptake by increasing medium osmolarity suggests transport into an osmotically reactive space rather than binding to the membranes. Electrogenecity of the sodium-sugar and sodium-amino-acid cotransport system was established by their dependence on artificially imposed diffusion potentials. Also a NA+/H+ antiport system can be demonstrated in microvilli vesicles by demonstrating counterflow of both ions under short circuit conditions. Basal-lateral plasma membranes contain sodium independent stereospecific transport systems for sugars and amino acids. These results demonstrate a marked functional polarity of the cell membranes in respect to sodium dependent and sodium independent transport systems. This polarity in conjunction with the asymmetrical distribution of sodium between the intra- and extracellular space seems to enable the proximal tubule epithelial cells to perform active transepithelial transport."}
{"id": "PMID:11965", "title": "Properties of rat kidney glutaminase enzymes and their role in renal ammoniagenesis.", "content": "Rat kidney contains two distinct glutaminase activities; the mitochondrial phosphate-dependent glutaminase and a second glutaminase activity associated with the brush border membrane which is maleate-activated and phosphate-independent. It has recently been shown that the phosphate-independent glutaminase is a partial reaction of gamma-glutamyl transpeptidase and that maleate activates this enzyme by blocking transpeptidation. The gamma-glutamyl transpeptidase in other rat tissues is also affected by maleate. This enzyme has at least a 100-fold greater affinity for glutathione or for glutathione derivatives than for glutamine, suggesting that under physiological conditions glutathione is the preferred substrate. With either type of substrate, maleate affects the Vmax of the reaction but not the Km. These findings suggest that this enzyme probably contributes very little to renal ammoniagenesis. In contrast, the phosphate-dependent glutaminase, whose activity increases 20 to 30-fold in the proximal convoluted tubule cells in response to metabolic acidosis, probably contributes significantly to renal ammoniagenesis. We have purified the rat kidney phosphate-dependent glutaminase and compared the phosphate activation and the phosphate-induced dimerization of the Tris form of this enzyme. There is an excellent correlation between increased activity and extent of dimerization as phosphate concentration is increased. The molecular weights of the Tris form are 1600000 and 316000 in the absence and presence of -1 M NaPO4, respectively. At saturating concentration of phosphate, increasing concentrations of chloride ion similarly reverse both activation and dimerization. These observations suggest that only the dimer form of the Tris enzyme is active.", "contents": "Properties of rat kidney glutaminase enzymes and their role in renal ammoniagenesis. Rat kidney contains two distinct glutaminase activities; the mitochondrial phosphate-dependent glutaminase and a second glutaminase activity associated with the brush border membrane which is maleate-activated and phosphate-independent. It has recently been shown that the phosphate-independent glutaminase is a partial reaction of gamma-glutamyl transpeptidase and that maleate activates this enzyme by blocking transpeptidation. The gamma-glutamyl transpeptidase in other rat tissues is also affected by maleate. This enzyme has at least a 100-fold greater affinity for glutathione or for glutathione derivatives than for glutamine, suggesting that under physiological conditions glutathione is the preferred substrate. With either type of substrate, maleate affects the Vmax of the reaction but not the Km. These findings suggest that this enzyme probably contributes very little to renal ammoniagenesis. In contrast, the phosphate-dependent glutaminase, whose activity increases 20 to 30-fold in the proximal convoluted tubule cells in response to metabolic acidosis, probably contributes significantly to renal ammoniagenesis. We have purified the rat kidney phosphate-dependent glutaminase and compared the phosphate activation and the phosphate-induced dimerization of the Tris form of this enzyme. There is an excellent correlation between increased activity and extent of dimerization as phosphate concentration is increased. The molecular weights of the Tris form are 1600000 and 316000 in the absence and presence of -1 M NaPO4, respectively. At saturating concentration of phosphate, increasing concentrations of chloride ion similarly reverse both activation and dimerization. These observations suggest that only the dimer form of the Tris enzyme is active."}
{"id": "PMID:11966", "title": "On the role of gamma-glutamyltransferase in renal tubular amino acid reabsorption.", "content": "The degradation of glutathione in the kidney of the rat was investigated in vivo and in vitro. When radioactive glutathione or its analogue ophthalmic acid was administered intravenously to mice or rats, the tripeptides were rapidly and completely degraded. Within the organs, no radioactive glutathione, but only labelled glycine was found. The main part of the degrading activity was localized in the kidney. Kidney homogenate degraded glutathione at a rate of 46.5 nmoles/min per mg of protein. This could be inhibited by the gamma-glutamyltransferase inhibitor serine-borate. Isolated renal tubules degraded the tripeptide at a rate of 18 nmoles/min/mg; this reaction was also inhibited by serine-borate. The whole activity was found in the particulate fraction (100000 xg). Glycine and gamma-glutamylglycine were identified as the radio-active products. The results indicate that gamma-glutamyltransferase is able to split glutathione extracellularly in the lumen of the tubule at a very high rate. It is concluded that the enzyme faces the luminal side of the brush border membrane with respect to its substrate gluthathione. This seems to be incompatible with a basic topological prerequisite for the in vivo function of the gamma-glutamyl cycle in renal tubular amino acid reabsorption.", "contents": "On the role of gamma-glutamyltransferase in renal tubular amino acid reabsorption. The degradation of glutathione in the kidney of the rat was investigated in vivo and in vitro. When radioactive glutathione or its analogue ophthalmic acid was administered intravenously to mice or rats, the tripeptides were rapidly and completely degraded. Within the organs, no radioactive glutathione, but only labelled glycine was found. The main part of the degrading activity was localized in the kidney. Kidney homogenate degraded glutathione at a rate of 46.5 nmoles/min per mg of protein. This could be inhibited by the gamma-glutamyltransferase inhibitor serine-borate. Isolated renal tubules degraded the tripeptide at a rate of 18 nmoles/min/mg; this reaction was also inhibited by serine-borate. The whole activity was found in the particulate fraction (100000 xg). Glycine and gamma-glutamylglycine were identified as the radio-active products. The results indicate that gamma-glutamyltransferase is able to split glutathione extracellularly in the lumen of the tubule at a very high rate. It is concluded that the enzyme faces the luminal side of the brush border membrane with respect to its substrate gluthathione. This seems to be incompatible with a basic topological prerequisite for the in vivo function of the gamma-glutamyl cycle in renal tubular amino acid reabsorption."}
{"id": "PMID:11967", "title": "The influence of branched chain aminoacids and their ketoderivatives on renal gluconeogenesis.", "content": "Isolated kidney tubules served as a model to investigate the direct effect of branched chain aminoacids and their ketoderivatives on gluconeogenesis. The data presented in this paper demonstrate that the ketoderivatives rather than the branched chain aminoacids themselves inhibit renal glucosesynthesis from various precursors entering the glucogenic pathway at different levels. Though the point of the inhibitory attack of ketoacids could not be localized, an impairement of the kidney cortex to respond to metabolic acidosis with an increase of gluconeogenesis is evident from the present data. The relevance of the presented data concerning the production of hypoglycemia and metabolic acidosis in leucine induced hypoglycemia and maple syrup urine disease is discussed.", "contents": "The influence of branched chain aminoacids and their ketoderivatives on renal gluconeogenesis. Isolated kidney tubules served as a model to investigate the direct effect of branched chain aminoacids and their ketoderivatives on gluconeogenesis. The data presented in this paper demonstrate that the ketoderivatives rather than the branched chain aminoacids themselves inhibit renal glucosesynthesis from various precursors entering the glucogenic pathway at different levels. Though the point of the inhibitory attack of ketoacids could not be localized, an impairement of the kidney cortex to respond to metabolic acidosis with an increase of gluconeogenesis is evident from the present data. The relevance of the presented data concerning the production of hypoglycemia and metabolic acidosis in leucine induced hypoglycemia and maple syrup urine disease is discussed."}
{"id": "PMID:11969", "title": "Human mitochondrial NADP-dependent isocitrate dehydrogenase in man-mouse somatic cell hybrids.", "content": "Human mitochondrial NADP-dependent isocitrate dehydrogenase (IDH-2) is expressed in man-mouse somatic cell hybrids as a dimeric molecule. The gene specifing this enzyme was observed to be syntenic with the mannose phosphate isomerase locus in the 56 primary man-mouse clones in this series. The human IDH-2 locus, therefore, may be assigned to chromosome 15.", "contents": "Human mitochondrial NADP-dependent isocitrate dehydrogenase in man-mouse somatic cell hybrids. Human mitochondrial NADP-dependent isocitrate dehydrogenase (IDH-2) is expressed in man-mouse somatic cell hybrids as a dimeric molecule. The gene specifing this enzyme was observed to be syntenic with the mannose phosphate isomerase locus in the 56 primary man-mouse clones in this series. The human IDH-2 locus, therefore, may be assigned to chromosome 15."}
{"id": "PMID:11970", "title": "Immediate hypersensitivity to tuberculin. In vivo and in vitro studies.", "content": "Immediate responses of hypersensitivity to skin testing with purified derivative of tuberculin (PPD) were observed in 2.3 percent of 3,248 patients seen in an allergy clinic, and the relationship to delayed responses was questioned. Immediate cutaneous reactions to testing with PPD appeared in all age groups and occurred in nonatopic patients but were more common in atopic patients (p less than 0.005). Delayed cutaneous reactions to testing with PPD occurred in only three out of 76 patients with immediate reactivity. Antihistaminic suppression of immediate reactivity was not followed by evidence of delayed cutaneous reactivity. In vitro tests of lymphocytic stimulation revealed indices of stimulation with PPD to be similar both in patients with immediate and delayed cutaneous reactivity. Failure to manifest delayed cutaneous reactivity following immediate cutaneous reactions alone may be explained by antigen-antibody binding and phagocytosis, by suppressor T-lymphocytes, or by impaired release or lack of response to T-lymphocytic mediators. Adverse reactions to administration of BCG vaccine in patients with immediate cutaneous reactivity might be anticipated.", "contents": "Immediate hypersensitivity to tuberculin. In vivo and in vitro studies. Immediate responses of hypersensitivity to skin testing with purified derivative of tuberculin (PPD) were observed in 2.3 percent of 3,248 patients seen in an allergy clinic, and the relationship to delayed responses was questioned. Immediate cutaneous reactions to testing with PPD appeared in all age groups and occurred in nonatopic patients but were more common in atopic patients (p less than 0.005). Delayed cutaneous reactions to testing with PPD occurred in only three out of 76 patients with immediate reactivity. Antihistaminic suppression of immediate reactivity was not followed by evidence of delayed cutaneous reactivity. In vitro tests of lymphocytic stimulation revealed indices of stimulation with PPD to be similar both in patients with immediate and delayed cutaneous reactivity. Failure to manifest delayed cutaneous reactivity following immediate cutaneous reactions alone may be explained by antigen-antibody binding and phagocytosis, by suppressor T-lymphocytes, or by impaired release or lack of response to T-lymphocytic mediators. Adverse reactions to administration of BCG vaccine in patients with immediate cutaneous reactivity might be anticipated."}
{"id": "PMID:11971", "title": "Organ and species differences in microsomal activation of methyldopa.", "content": "The covalent binding of 3H-methyldopa to microsomal protein in the presence of NADHP and oxygen was studied in various microsomal preparations. Rat and mouse liver microsomes showed high binding, hamster and guinea pig liver microsomes gave intermediate values, whereas no binding was seen with rabbit liver microsomes. No activation of methyldopa was detected with kidney microsomes. Lung microsomes from rats, guinea pigs, and rabbits were quite active with respect to methyldopa binding, and the reactions were totally blocked by superoxide dismutase. There was no sex difference in the binding of methyldopa in liver microsomes from adult rats. No methyldopa activation could be detected in fetal liver microsomes, whereas a rapid increase in activity to above adult levels occurred during the first 2 days after birth.", "contents": "Organ and species differences in microsomal activation of methyldopa. The covalent binding of 3H-methyldopa to microsomal protein in the presence of NADHP and oxygen was studied in various microsomal preparations. Rat and mouse liver microsomes showed high binding, hamster and guinea pig liver microsomes gave intermediate values, whereas no binding was seen with rabbit liver microsomes. No activation of methyldopa was detected with kidney microsomes. Lung microsomes from rats, guinea pigs, and rabbits were quite active with respect to methyldopa binding, and the reactions were totally blocked by superoxide dismutase. There was no sex difference in the binding of methyldopa in liver microsomes from adult rats. No methyldopa activation could be detected in fetal liver microsomes, whereas a rapid increase in activity to above adult levels occurred during the first 2 days after birth."}
{"id": "PMID:11972", "title": "Xenobiotic metabolism and enzyme induction in isolated rat intestinal microsomes.", "content": "Intestinal microsomes were isolated from rats pretreated with 3-methylcholanthrene (MC), phenobarbital (PB), and pregnenolone-16alpha-carbonitrile (PCN). The metabolism of benzo[a]pyrene (BP), 7-ethoxyresorufin, 7-ethoxycoumarin, and biphenyl were examined. MC induces a 30-fold increase in BP metabolism. With control microsomes, BP metabolism is inhibited by metyrapone, SKF 525-A, and antimycin A, but is stimulated 4.5-fold by rotenone. With microsomes from MC-treated rats, BP metabolism is inhibited by metyrapone, SKF 525-A, antimycin A, and rotenone. MC pretreatment increases 7-ethoxyresorufin de-ethylase by almost 20-fold and ethoxycoumarin de-ethylase by almost 18 fold. PB pretreatment produces less than a 2-fold increase in both de-ethylases. PCN pretreatment inhibits 7-ethoxyresorufin and 7-ethoxycoumarin de-ethylases. In rats fasted for 2 days, neither de-ethylase could be detected in intestinal microsomes. Biphenyl 2- and 4-hydroxylase activities were induced less than 4-fold by MC or PB pretreatment.", "contents": "Xenobiotic metabolism and enzyme induction in isolated rat intestinal microsomes. Intestinal microsomes were isolated from rats pretreated with 3-methylcholanthrene (MC), phenobarbital (PB), and pregnenolone-16alpha-carbonitrile (PCN). The metabolism of benzo[a]pyrene (BP), 7-ethoxyresorufin, 7-ethoxycoumarin, and biphenyl were examined. MC induces a 30-fold increase in BP metabolism. With control microsomes, BP metabolism is inhibited by metyrapone, SKF 525-A, and antimycin A, but is stimulated 4.5-fold by rotenone. With microsomes from MC-treated rats, BP metabolism is inhibited by metyrapone, SKF 525-A, antimycin A, and rotenone. MC pretreatment increases 7-ethoxyresorufin de-ethylase by almost 20-fold and ethoxycoumarin de-ethylase by almost 18 fold. PB pretreatment produces less than a 2-fold increase in both de-ethylases. PCN pretreatment inhibits 7-ethoxyresorufin and 7-ethoxycoumarin de-ethylases. In rats fasted for 2 days, neither de-ethylase could be detected in intestinal microsomes. Biphenyl 2- and 4-hydroxylase activities were induced less than 4-fold by MC or PB pretreatment."}
{"id": "PMID:11973", "title": "The rat brain as a \"deep compartment\" in the kinetics of a common metabolite of prochlorperazine and perphenazine.", "content": "N-[gamma-(2-Chlorophenothiazin-10-yl)propyl]ethylenediamine (Cl-PPED), a common metabolite of prochlorperazine and perphenazine, was orally administered to male rats  at a dose of 50 mg/kg, and its concentrations in plasma, liver, lung, kidney, and brain were followed from 6 hr to 40 days after dosage. Small quantities were measured by two-dimensional thin-layer chromatography of a fluorescent derivative and in situ fluorometry of the chromatograms. The kinetic behavior of Cl-PPED in brain differed from that in other tissues in that the concentration maximum was  achieved later and the elimination half-life was distinctly longer (8 days vs. 1.2-3 days). Cl-PPED was evenly among the three major brain regions. Subcellular fractionation of liver and brain revealed preferential localization in mitochondria.", "contents": "The rat brain as a \"deep compartment\" in the kinetics of a common metabolite of prochlorperazine and perphenazine. N-[gamma-(2-Chlorophenothiazin-10-yl)propyl]ethylenediamine (Cl-PPED), a common metabolite of prochlorperazine and perphenazine, was orally administered to male rats  at a dose of 50 mg/kg, and its concentrations in plasma, liver, lung, kidney, and brain were followed from 6 hr to 40 days after dosage. Small quantities were measured by two-dimensional thin-layer chromatography of a fluorescent derivative and in situ fluorometry of the chromatograms. The kinetic behavior of Cl-PPED in brain differed from that in other tissues in that the concentration maximum was  achieved later and the elimination half-life was distinctly longer (8 days vs. 1.2-3 days). Cl-PPED was evenly among the three major brain regions. Subcellular fractionation of liver and brain revealed preferential localization in mitochondria."}
{"id": "PMID:11974", "title": "Localization of nicotine-14C, cotinine-14C, and nicotine-1'-N-oxide-14C in tissues of the mouse.", "content": "The distrubutions of nicotine-14C (2'- or methyl-labeled), cotinine-14C, and nicotine-1'-N-oxide-14C were studied by whole-body autoradiography in mice and in perfused rabbit lung. The compounds were administered either iv, sc, ip, or by inhalation. Blank sections were also incubated with nicotine-14C and cotinine-14C in vitro. The distributions were compared in a black (C57BL/6J), brown (C57L/J), and albino (A/HeJ) strain and in CD-1 germ-free mice. After administration of nicotine-14C in vivo, radioactivity was localized in all strains in bronchi, nasal mucosa, salivary gland, Harder's gland, liver, kidney, stomach, spleen, pancreas, intestine, bone, gallbladder, and adrenal medulla. In the pigmented strains, it was also localized in melanin in the eye, brain, and hair. Radioactivity did not accumulate in the bronchi of late-term fetuses or the 1-day-old newborn but was present in the 2-day-old and older. Cotinine-14C and nicotine-1'-N-oxide-14C, after iv administration, did not localize in bronchi or nasal mucosa at short time intervals after injection. Frozen sections incubated in vitro did not accumulate either nicotine-14C or cotinine-14C in the bronchi; whereas the affinity for melanin was unchanged. Incubation of fresh, nonfrozen mouse lung and perfusion of rabbit lung in vitro with nicotine-14C produced the same localization of radioactivity in bronchi as that seen after in vivo administration. Preheating the frozen sections or lungs in a microwave oven before incubation did not change the localization of radioactivity in the bronchi or other tissues. The localization of radioactivity in bronchi may be due to metabolism, active transport, or binding of nicotine; this mechanism is destroyed by freezing the tissue.", "contents": "Localization of nicotine-14C, cotinine-14C, and nicotine-1'-N-oxide-14C in tissues of the mouse. The distrubutions of nicotine-14C (2'- or methyl-labeled), cotinine-14C, and nicotine-1'-N-oxide-14C were studied by whole-body autoradiography in mice and in perfused rabbit lung. The compounds were administered either iv, sc, ip, or by inhalation. Blank sections were also incubated with nicotine-14C and cotinine-14C in vitro. The distributions were compared in a black (C57BL/6J), brown (C57L/J), and albino (A/HeJ) strain and in CD-1 germ-free mice. After administration of nicotine-14C in vivo, radioactivity was localized in all strains in bronchi, nasal mucosa, salivary gland, Harder's gland, liver, kidney, stomach, spleen, pancreas, intestine, bone, gallbladder, and adrenal medulla. In the pigmented strains, it was also localized in melanin in the eye, brain, and hair. Radioactivity did not accumulate in the bronchi of late-term fetuses or the 1-day-old newborn but was present in the 2-day-old and older. Cotinine-14C and nicotine-1'-N-oxide-14C, after iv administration, did not localize in bronchi or nasal mucosa at short time intervals after injection. Frozen sections incubated in vitro did not accumulate either nicotine-14C or cotinine-14C in the bronchi; whereas the affinity for melanin was unchanged. Incubation of fresh, nonfrozen mouse lung and perfusion of rabbit lung in vitro with nicotine-14C produced the same localization of radioactivity in bronchi as that seen after in vivo administration. Preheating the frozen sections or lungs in a microwave oven before incubation did not change the localization of radioactivity in the bronchi or other tissues. The localization of radioactivity in bronchi may be due to metabolism, active transport, or binding of nicotine; this mechanism is destroyed by freezing the tissue."}
{"id": "PMID:11975", "title": "Effect of sex hormones on the disposition in rats of 1-aminocyclohexane carboxylic acid, a metabolite of semisynthetic penicillin.", "content": "The renal clearance of 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of the semisynthetic penicillin, cyclacillin, is about 10 times faster in female than in male rats. The slower clearance in males is attributed to a higher net rate of reabsorption of the compound from the tubule of the kidney. Because ACHC is not metabolized, it is apparently continuously recirculated through the kidney of the male, resulting in the longer half-life. The sex-related disposition of the metabolite can be modified by gonadectomy and/or treatment with sex hormones. Castrated males show increased urinary excretion and decreased plasma half-life of  ACHC relative to intact males. In ovariectomized females, less ACHC is excreted and the half-life is longer than in intact females. Thus, in both sexes, gonadectomy shifts the excretion and the residence time in plasma toward the values of these parameters for the opposite sex. Treatment of castrated males with estradiol markedly enhances the effect of castration, but treatment of ovariectomized females with testosterone propionate has little or no additional effect over ovariectomy. Treatment of intact males with estradiol modifies both excretion and residence time in plasma to a great extent, but treatment of intact females with testosterone has a lesser effect on the disposition of ACHC. These results indicate that excretion and residence time of ACHC in both male and female rats are influenced by sex hormones. The described effect is an example of the action of sex hormones on the transport of foreign compounds in this species. Its mechanism is quite different from the well known influence of sex hormones on the microsomal metabolism of foreign compounds in rats.", "contents": "Effect of sex hormones on the disposition in rats of 1-aminocyclohexane carboxylic acid, a metabolite of semisynthetic penicillin. The renal clearance of 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of the semisynthetic penicillin, cyclacillin, is about 10 times faster in female than in male rats. The slower clearance in males is attributed to a higher net rate of reabsorption of the compound from the tubule of the kidney. Because ACHC is not metabolized, it is apparently continuously recirculated through the kidney of the male, resulting in the longer half-life. The sex-related disposition of the metabolite can be modified by gonadectomy and/or treatment with sex hormones. Castrated males show increased urinary excretion and decreased plasma half-life of  ACHC relative to intact males. In ovariectomized females, less ACHC is excreted and the half-life is longer than in intact females. Thus, in both sexes, gonadectomy shifts the excretion and the residence time in plasma toward the values of these parameters for the opposite sex. Treatment of castrated males with estradiol markedly enhances the effect of castration, but treatment of ovariectomized females with testosterone propionate has little or no additional effect over ovariectomy. Treatment of intact males with estradiol modifies both excretion and residence time in plasma to a great extent, but treatment of intact females with testosterone has a lesser effect on the disposition of ACHC. These results indicate that excretion and residence time of ACHC in both male and female rats are influenced by sex hormones. The described effect is an example of the action of sex hormones on the transport of foreign compounds in this species. Its mechanism is quite different from the well known influence of sex hormones on the microsomal metabolism of foreign compounds in rats."}
{"id": "PMID:11976", "title": "Species differences in the metabolism and disposition of spironolactone.", "content": "The absorption, excretion and metabolism of [22-14C]spironolactone was compared in Charles River rats, beagle dogs and rhesus monkeys. The drug was administered at the fixed dose of 5 mg/kg po and iv. From the po/iv ratios of the areas under the plasma radioactivity-time curves, the gastrointestinal absorption of the drug was estimated to be 82% in the rat, 62% in the dog, and 103% in the monkey. The absolute bioavailability of a pharmacologically active metabolite, canrenone, was 57% in the dog and 48% in the monkey. Spironolactone was extensively metabolized in all three species and differences existed in the composition of the metabolites in their plasma, urine, and feces. The amount of radioactivity that was excreted in the urine and feces of all three species was similar after either po or iv administration of the drug. The cumulative average excretion of radioactivity in the urine as percentage of the po dose in 6 days was 4.69% in the rat (N = 5), 18.5% in the dog (N = 3), and 46.0% in the monkey (N = 3). In the feces, the corresponding excretion values were 74.2, 69.3 and 40.1%, respectively. Canrenone excretion in the urine constituted 0.65% of the po dose in the rat, 0.82% in the dog, and 5.86% in the monkey, whereas the excretion of total fluorogenic metabolites constituted 1.1, 1.9, and 12.1% respectively. Comparison of animal data with those published for humans indicated that the disposition and metabolism of spironolactone in the rhesus monkey, rather than those in the rat or the dog, was closest to that in man.", "contents": "Species differences in the metabolism and disposition of spironolactone. The absorption, excretion and metabolism of [22-14C]spironolactone was compared in Charles River rats, beagle dogs and rhesus monkeys. The drug was administered at the fixed dose of 5 mg/kg po and iv. From the po/iv ratios of the areas under the plasma radioactivity-time curves, the gastrointestinal absorption of the drug was estimated to be 82% in the rat, 62% in the dog, and 103% in the monkey. The absolute bioavailability of a pharmacologically active metabolite, canrenone, was 57% in the dog and 48% in the monkey. Spironolactone was extensively metabolized in all three species and differences existed in the composition of the metabolites in their plasma, urine, and feces. The amount of radioactivity that was excreted in the urine and feces of all three species was similar after either po or iv administration of the drug. The cumulative average excretion of radioactivity in the urine as percentage of the po dose in 6 days was 4.69% in the rat (N = 5), 18.5% in the dog (N = 3), and 46.0% in the monkey (N = 3). In the feces, the corresponding excretion values were 74.2, 69.3 and 40.1%, respectively. Canrenone excretion in the urine constituted 0.65% of the po dose in the rat, 0.82% in the dog, and 5.86% in the monkey, whereas the excretion of total fluorogenic metabolites constituted 1.1, 1.9, and 12.1% respectively. Comparison of animal data with those published for humans indicated that the disposition and metabolism of spironolactone in the rhesus monkey, rather than those in the rat or the dog, was closest to that in man."}
{"id": "PMID:11977", "title": "The formation of cytochrome P-450-metabolic intermediate complexes in microsomal fractions from extrahepatic tissues of the rabbit.", "content": "Cytochrome P-450-metabolic intermediate complexes were formed from N-hydroxyamphetamine, benzphetamine, norbenzphetamine, and d- and l-amphetamine in lung microsomal fractions and from N-hydroxyamphetamine in small intestinal mucosa microsomal fractions. Complexes were not formed in either tissue from SKF 525-A or propoxyphene. The rates of metabolic intermediate complex formation, per mole of cytochrome P-450, were higher in lung than in liver or small intestine. In contrast to that in liver, metabolic intermediate complex formation in the extrahepatic tissues was not dramatically affected by phenobarbital or 3-methylcholanthrene treatment.", "contents": "The formation of cytochrome P-450-metabolic intermediate complexes in microsomal fractions from extrahepatic tissues of the rabbit. Cytochrome P-450-metabolic intermediate complexes were formed from N-hydroxyamphetamine, benzphetamine, norbenzphetamine, and d- and l-amphetamine in lung microsomal fractions and from N-hydroxyamphetamine in small intestinal mucosa microsomal fractions. Complexes were not formed in either tissue from SKF 525-A or propoxyphene. The rates of metabolic intermediate complex formation, per mole of cytochrome P-450, were higher in lung than in liver or small intestine. In contrast to that in liver, metabolic intermediate complex formation in the extrahepatic tissues was not dramatically affected by phenobarbital or 3-methylcholanthrene treatment."}
{"id": "PMID:11978", "title": "Identification of basic metabolites of 4-[4-(p-chlo- robenzoyl)piperidino]-4'-fluorobutyrophenone, an experimental neuroleptic agent.", "content": "Two metabolites of 4-[4-(p-(chlorobenzoyl)piperidino]-4'-fluorobutyrophenone (RMI 9901) as well as unchanged drug, have been identified in the urine of rats following oral administration of the drug. Analysis of basic urine extracts by combined gas chromatography-mass spectrometry was employed for metabolite identification. N-dealkylation appears to be a major metabolic pathway and results in formation of 4-(p-chlorobenzoyl)piperidine (I). Subsequent oxidation of this metabolite results in the formation of 4-(p-chlorobenzoyl)-2-piperidone (II), and represents rather unusual metabolic pathway for compounds of this chemical class.", "contents": "Identification of basic metabolites of 4-[4-(p-chlo- robenzoyl)piperidino]-4'-fluorobutyrophenone, an experimental neuroleptic agent. Two metabolites of 4-[4-(p-(chlorobenzoyl)piperidino]-4'-fluorobutyrophenone (RMI 9901) as well as unchanged drug, have been identified in the urine of rats following oral administration of the drug. Analysis of basic urine extracts by combined gas chromatography-mass spectrometry was employed for metabolite identification. N-dealkylation appears to be a major metabolic pathway and results in formation of 4-(p-chlorobenzoyl)piperidine (I). Subsequent oxidation of this metabolite results in the formation of 4-(p-chlorobenzoyl)-2-piperidone (II), and represents rather unusual metabolic pathway for compounds of this chemical class."}
{"id": "PMID:11982", "title": "[Serum-gastrin levels and gastric-acid secretion in infants (author's transl)].", "content": "Gastric acid secretion was measured in 20 infants aged 6-438 days. The values for the basal acid output and that after stimulation with 6 mug/kg pentagastrin subcutaneously were found to be related to age, body weight and body surface area. But these correlations were not comparable to those in adults. Standard values for different age groups in childhood must therefore be established. Furthermore, the results indicate parietal-cell immaturity during the first six months of life. Measurement of fasting serum-gastrin concentration by radioimmunoassay in 74 infants, aged 1-438 days, and 154 adults as controls revealed a high serum-gastrin level in infants, with an exponential decrease during the first year of life. Despite comparable pH values in gastric juice at one year of life, the gastrin concentrations were higher than those in adults (at a statistically significant level). On the other hand, normal serum-gastrin concentrations were found in ten pregnant women just before delivery. The results suggest a negative feed-back mechanism between gastric-acid secretion and fasting serum-gastrin levels, but such mechanism probably being limited by extragastric gastrin secretion.", "contents": "[Serum-gastrin levels and gastric-acid secretion in infants (author's transl)]. Gastric acid secretion was measured in 20 infants aged 6-438 days. The values for the basal acid output and that after stimulation with 6 mug/kg pentagastrin subcutaneously were found to be related to age, body weight and body surface area. But these correlations were not comparable to those in adults. Standard values for different age groups in childhood must therefore be established. Furthermore, the results indicate parietal-cell immaturity during the first six months of life. Measurement of fasting serum-gastrin concentration by radioimmunoassay in 74 infants, aged 1-438 days, and 154 adults as controls revealed a high serum-gastrin level in infants, with an exponential decrease during the first year of life. Despite comparable pH values in gastric juice at one year of life, the gastrin concentrations were higher than those in adults (at a statistically significant level). On the other hand, normal serum-gastrin concentrations were found in ten pregnant women just before delivery. The results suggest a negative feed-back mechanism between gastric-acid secretion and fasting serum-gastrin levels, but such mechanism probably being limited by extragastric gastrin secretion."}
{"id": "PMID:11979", "title": "Metabolism of methoxyphenamine in man and in monkey.", "content": "Metabolites of methoxyphenamine in the urine of human subjects and monkeys were separated by gas-liquid chromatography and identified by comparison of their chromatographic and mass spectrometric behavior with those of synthetic compounds. Aromatic O-demethylation, aromatic ring hydroxylation (both followed by glucuronide conjugation), and N-demethylation were shown to occur in man as well as in monkey. In man these were the principal metabolites, whereas in the monkey three additional unidentified major metabolites were formed.", "contents": "Metabolism of methoxyphenamine in man and in monkey. Metabolites of methoxyphenamine in the urine of human subjects and monkeys were separated by gas-liquid chromatography and identified by comparison of their chromatographic and mass spectrometric behavior with those of synthetic compounds. Aromatic O-demethylation, aromatic ring hydroxylation (both followed by glucuronide conjugation), and N-demethylation were shown to occur in man as well as in monkey. In man these were the principal metabolites, whereas in the monkey three additional unidentified major metabolites were formed."}
{"id": "PMID:11980", "title": "A method for the measurement of L-phenylalanine mustard in the mouse and dog by high-pressure liquid chromatography.", "content": "The distribution of L-phenylalanine mustard (L-PAM) was studied in dogs and mice by high-pressure liquid chromatography. Separation of L-PAM from its products of hydrolysis was accomplished with a mu-Bondapak C18 column, a solvent system composed of 2-methoxyethanol/0.1% acetic acid, and solvent programming with a step gradient. Complete separation was effected in less than 15 min. The half-life for disappearance of L-PAM from mouse blood was 41 min, whereas that from dog blood was 29 min. The monohydroxy derivative of L-PAM, L-MOH, disappeared from dog serum with a half-life of 32 min. L-MOH was not detectable in mouse tissue other than blood at times greater than 15 min after injection. In the dog at 4 hr after injection, the tissue/serum concentration ratios were greater than 1 for liver, spleen, intestine, skeletal muscle, urinary bladder and gallbladder. The concentration of L-PAM in the bile was approximately 500 times higher than that in serum.", "contents": "A method for the measurement of L-phenylalanine mustard in the mouse and dog by high-pressure liquid chromatography. The distribution of L-phenylalanine mustard (L-PAM) was studied in dogs and mice by high-pressure liquid chromatography. Separation of L-PAM from its products of hydrolysis was accomplished with a mu-Bondapak C18 column, a solvent system composed of 2-methoxyethanol/0.1% acetic acid, and solvent programming with a step gradient. Complete separation was effected in less than 15 min. The half-life for disappearance of L-PAM from mouse blood was 41 min, whereas that from dog blood was 29 min. The monohydroxy derivative of L-PAM, L-MOH, disappeared from dog serum with a half-life of 32 min. L-MOH was not detectable in mouse tissue other than blood at times greater than 15 min after injection. In the dog at 4 hr after injection, the tissue/serum concentration ratios were greater than 1 for liver, spleen, intestine, skeletal muscle, urinary bladder and gallbladder. The concentration of L-PAM in the bile was approximately 500 times higher than that in serum."}
{"id": "PMID:11984", "title": "[Lactic acidosis in diabetics on biguanides (author's transl)].", "content": "A systematic search for cases of lactic acidosis among diabetics on biguanides revealed ten during an eight-month period, while in the preceding ten years not a single case had been definitely diagnosed. This represents a prevelance of 1 in 2000 patients admitted to hospital. All ten were over 60 years old and had previously been treated for heart failure. Most of them had suffered from renal insufficiency for some time. There was no case of biguanide overdosage. Criteria for the diagnosis of lactic acidosis are lactic concentration in blood averaging 18.4 mmol/l and a low pH, averaging 6.9. Serum-biguanide concentration (measured by radioimmuno-assay) was markedly increased. Most of the patients were in circulatory shock on admission or soon after and all of them had a history of gastro-intestinal complaints. Despite intensive treatment with insulin and glucose and careful correction of the acidosis with bicarbonate four of the ten patients died.", "contents": "[Lactic acidosis in diabetics on biguanides (author's transl)]. A systematic search for cases of lactic acidosis among diabetics on biguanides revealed ten during an eight-month period, while in the preceding ten years not a single case had been definitely diagnosed. This represents a prevelance of 1 in 2000 patients admitted to hospital. All ten were over 60 years old and had previously been treated for heart failure. Most of them had suffered from renal insufficiency for some time. There was no case of biguanide overdosage. Criteria for the diagnosis of lactic acidosis are lactic concentration in blood averaging 18.4 mmol/l and a low pH, averaging 6.9. Serum-biguanide concentration (measured by radioimmuno-assay) was markedly increased. Most of the patients were in circulatory shock on admission or soon after and all of them had a history of gastro-intestinal complaints. Despite intensive treatment with insulin and glucose and careful correction of the acidosis with bicarbonate four of the ten patients died."}
{"id": "PMID:11986", "title": "[Alcohol-psychotropic drug interactions].", "content": "The problem of ethanol interactions with psychotropic drugs involves various factors whose complex action is examined in this article. Great care should be taken with regard to the alcohol consumption among patients treated with sedatives; the depressive action of ethanol on the central nervous system could be potentiated especially at the beginning of the treatment, as it seems that a certain habituation to the interactions may exist. However, one should be aware that the personality of the patient is perhaps more important to take into account that the consumption of drugs, at least as regards to the factors of risk in traffic accidents. Parallel to the interactions involving the receptors of the central nervous system, metabolic interactions are possible, however more difficult to describe: they affect drugs absorption, their hepatic metabolism and seem to act especially in chronic alcoholism or during barbiturates consumption.", "contents": "[Alcohol-psychotropic drug interactions]. The problem of ethanol interactions with psychotropic drugs involves various factors whose complex action is examined in this article. Great care should be taken with regard to the alcohol consumption among patients treated with sedatives; the depressive action of ethanol on the central nervous system could be potentiated especially at the beginning of the treatment, as it seems that a certain habituation to the interactions may exist. However, one should be aware that the personality of the patient is perhaps more important to take into account that the consumption of drugs, at least as regards to the factors of risk in traffic accidents. Parallel to the interactions involving the receptors of the central nervous system, metabolic interactions are possible, however more difficult to describe: they affect drugs absorption, their hepatic metabolism and seem to act especially in chronic alcoholism or during barbiturates consumption."}
{"id": "PMID:11987", "title": "Developmental changes in serum luteinizing hormone, follicle stimulating hormone and androgen levels in males of two inbred mouse strains.", "content": "A comprehensive developmental study of serum LH, FSH and androgen concentrations was carried out in male mice of two inbred strains. Gonadotropic hormone (GTH) levels rose 10-15 days prior to the pubertal increase in serum androgen with FSH preceding LH in this regard. In both strains GTH titer rose to a peak at 30 or 35 days and then steadily declined to adult levels which were strain-specific. Serum androgen was detected at low, relatively steady levels until the pubertal increase between 30 and 50 days postpartum. The results are interpreted as supporting the hypothesis that a shift in feedback sensitivity, occurring at about 20 days of age, may be involved in the onset of puberty in the male mouse.", "contents": "Developmental changes in serum luteinizing hormone, follicle stimulating hormone and androgen levels in males of two inbred mouse strains. A comprehensive developmental study of serum LH, FSH and androgen concentrations was carried out in male mice of two inbred strains. Gonadotropic hormone (GTH) levels rose 10-15 days prior to the pubertal increase in serum androgen with FSH preceding LH in this regard. In both strains GTH titer rose to a peak at 30 or 35 days and then steadily declined to adult levels which were strain-specific. Serum androgen was detected at low, relatively steady levels until the pubertal increase between 30 and 50 days postpartum. The results are interpreted as supporting the hypothesis that a shift in feedback sensitivity, occurring at about 20 days of age, may be involved in the onset of puberty in the male mouse."}
{"id": "PMID:11988", "title": "Corticotropin releasing factor distribution in normal and Brattleboro rat brain, and effect of deafferentation, hypophysectomy and steroid treatment in normal animals.", "content": "Corticotropin-Releasing Factor (CRF) activity was determined (dispersed pituitary cell assay) in rat median eminence (ME), various hypothalamic nuclei, as well as in entire median basal hypothalamus (MBH) and extra-hypothalamic areas. Highest concentrations were seen in ME, with decreased concentrations noted proceeding dorsally and cephalad from ME. Potency (NIAMDD HE-RP-1, ME reference extract, equivalent to 1.0) estimates were: ME-2.2; arcuate n.-0.88; dorsomedial n.-041; ventromedial n.-0.35; periventricular n.-0.24; hypothalamus-0.05; thalamus-0.01; cortex-0.005. Measurable, but lesser amounts, than in the above cited nuclei, were present in supraoptic and paraventricular nuclei. CRF activity was not measurable in preoptic area, septum, olfactory bulb, striatum, mesencephalon, pons, medulla or cerebellum. Complete hypothalamic deafferentation was accompanied by an increase in CRF activity/mug protein in ME and MBH, associated with decreased AM plasma ACTH and corticosterone concentrations. CRF-like activity in ME and MBH increased following hypophysectomy and after dexamethasone pretreatment. These findings indicate that CRF is mainly synthesized in the ME and surrounding area, and this source of CRF is sensitive to feedback effects and that extrahypothalamic inputs affect CRF release. Female animals had higher ME CRF content than did male animals. Homozygous and heterozygous Brattleboro rats had significantly less CRF in ME and MBH than did control animals, with significant differences also noted between homozygous and heterozygous animals.", "contents": "Corticotropin releasing factor distribution in normal and Brattleboro rat brain, and effect of deafferentation, hypophysectomy and steroid treatment in normal animals. Corticotropin-Releasing Factor (CRF) activity was determined (dispersed pituitary cell assay) in rat median eminence (ME), various hypothalamic nuclei, as well as in entire median basal hypothalamus (MBH) and extra-hypothalamic areas. Highest concentrations were seen in ME, with decreased concentrations noted proceeding dorsally and cephalad from ME. Potency (NIAMDD HE-RP-1, ME reference extract, equivalent to 1.0) estimates were: ME-2.2; arcuate n.-0.88; dorsomedial n.-041; ventromedial n.-0.35; periventricular n.-0.24; hypothalamus-0.05; thalamus-0.01; cortex-0.005. Measurable, but lesser amounts, than in the above cited nuclei, were present in supraoptic and paraventricular nuclei. CRF activity was not measurable in preoptic area, septum, olfactory bulb, striatum, mesencephalon, pons, medulla or cerebellum. Complete hypothalamic deafferentation was accompanied by an increase in CRF activity/mug protein in ME and MBH, associated with decreased AM plasma ACTH and corticosterone concentrations. CRF-like activity in ME and MBH increased following hypophysectomy and after dexamethasone pretreatment. These findings indicate that CRF is mainly synthesized in the ME and surrounding area, and this source of CRF is sensitive to feedback effects and that extrahypothalamic inputs affect CRF release. Female animals had higher ME CRF content than did male animals. Homozygous and heterozygous Brattleboro rats had significantly less CRF in ME and MBH than did control animals, with significant differences also noted between homozygous and heterozygous animals."}
{"id": "PMID:11989", "title": "The insulin receptor of the turkey erythrocyte: similarity to mammalian insulin receptors.", "content": "Avian erythrocytes possess insulin receptors which have binding properties that are virtually identical to those of the well studied mammalian insulin receptors. The affinity for porcine insulin was identical for the turkey and mammalian receptors over the entire range of insulin concentrations, as was the affinity of each of four insulin analogues which differed 300-fold in biological potency. Insulin induced acceleration of dissociation (i.e., the negatively cooperativite site-site interaction) was indistinguishable over a 10(6) range of insulin concentrations. Sharp pH dependence of binding was identical for turkey and mammalian receptors. The effects of temperature on association, dissociation and steady state binding were also identical. Thus, although birds and mammals have evolved separately for 300 million years there has been little change in the properties of the insulin receptor over this time period.", "contents": "The insulin receptor of the turkey erythrocyte: similarity to mammalian insulin receptors. Avian erythrocytes possess insulin receptors which have binding properties that are virtually identical to those of the well studied mammalian insulin receptors. The affinity for porcine insulin was identical for the turkey and mammalian receptors over the entire range of insulin concentrations, as was the affinity of each of four insulin analogues which differed 300-fold in biological potency. Insulin induced acceleration of dissociation (i.e., the negatively cooperativite site-site interaction) was indistinguishable over a 10(6) range of insulin concentrations. Sharp pH dependence of binding was identical for turkey and mammalian receptors. The effects of temperature on association, dissociation and steady state binding were also identical. Thus, although birds and mammals have evolved separately for 300 million years there has been little change in the properties of the insulin receptor over this time period."}
{"id": "PMID:11990", "title": "Pyridine nucleotides in pancreatic islets during inhibition of insulin release by exogenous insulin.", "content": "In vitro addition of rat insulin (200, 400 or 800 muU/ml) to collagenase-isolated pancreatic islets of adult rats diminished glucose (3 mg/ml)-induced insulin release which was correlated with a decrease of the ratio of total NADPH/NADP and inhibition of glucose oxidation via the pentose phosphate shunt (PPS). NADH and NAD levels were not affected. It is suggested that exogenous insulin diminishes the islet total NADPH/NADP ratio by a direct or indirect decrease in PPS activity. However, it is also conceivable that insulin decreases this ratio through another mechanism than PPS. It is possible that inhibition of insulin secretion by exogenous insulin is at least in part due to the decrease of the NADPH/NADP ratio.", "contents": "Pyridine nucleotides in pancreatic islets during inhibition of insulin release by exogenous insulin. In vitro addition of rat insulin (200, 400 or 800 muU/ml) to collagenase-isolated pancreatic islets of adult rats diminished glucose (3 mg/ml)-induced insulin release which was correlated with a decrease of the ratio of total NADPH/NADP and inhibition of glucose oxidation via the pentose phosphate shunt (PPS). NADH and NAD levels were not affected. It is suggested that exogenous insulin diminishes the islet total NADPH/NADP ratio by a direct or indirect decrease in PPS activity. However, it is also conceivable that insulin decreases this ratio through another mechanism than PPS. It is possible that inhibition of insulin secretion by exogenous insulin is at least in part due to the decrease of the NADPH/NADP ratio."}
{"id": "PMID:11991", "title": "Binding of nuclear triiodothyronine (T3) binding protein-T3 complex to chromatin.", "content": "Nuclear tirrodothyronine (T3) binding protein (NTBP)-T3 complex, prepared from liver nuclei of rats given [125I]T3 in vovo, rebinds to rat nuclear chromatin at pH 7.4 and at low, but not high, KCl concentrations. Liver NTBP-T3 complex binds to chromatin from liver, kidney, heart, brain, testis, and spleen. Binding was depressed at pH8, by addition of 10 mm CaCl2 or 100 mM MgCl2, and by 1 mM GTP or UTP. Although heart chromatin bound the most NTBP-T3 complex and brain the least, there is no clear separation of binding activity on comparison of three T3-responsive tissues (heart, liver, kidney) to the T3 insensitive tissues. Under the conditions of these experiments, there was no evident competition for binding sites on any of the six chromatins tested.", "contents": "Binding of nuclear triiodothyronine (T3) binding protein-T3 complex to chromatin. Nuclear tirrodothyronine (T3) binding protein (NTBP)-T3 complex, prepared from liver nuclei of rats given [125I]T3 in vovo, rebinds to rat nuclear chromatin at pH 7.4 and at low, but not high, KCl concentrations. Liver NTBP-T3 complex binds to chromatin from liver, kidney, heart, brain, testis, and spleen. Binding was depressed at pH8, by addition of 10 mm CaCl2 or 100 mM MgCl2, and by 1 mM GTP or UTP. Although heart chromatin bound the most NTBP-T3 complex and brain the least, there is no clear separation of binding activity on comparison of three T3-responsive tissues (heart, liver, kidney) to the T3 insensitive tissues. Under the conditions of these experiments, there was no evident competition for binding sites on any of the six chromatins tested."}
{"id": "PMID:11992", "title": "Teratopsychogenetic effects apparently produced by nonphysiological neurotransmitter concentrations during brain differentiation.", "content": "In male rats treated with pargyline, reserpine or pyridostigmine during neonatal life significant permanent changes of sexual behaviour and conditioned learning behaviour were observed in juvenile and/or adult life. Male sexual activity and learning capacity were permanently decreased in neonatally pargyline- or reserpine-treated animals, but permanently increased in neonatally pyridostigmine-treated rats. These findings suggest that nonphysiological concentrations and/or turnover rates of neurotransmitters, if produced during a critical period of brain differentiation, are able to induce lifelond effective behavioural changes, i.e. teratopsychogenetic effects.", "contents": "Teratopsychogenetic effects apparently produced by nonphysiological neurotransmitter concentrations during brain differentiation. In male rats treated with pargyline, reserpine or pyridostigmine during neonatal life significant permanent changes of sexual behaviour and conditioned learning behaviour were observed in juvenile and/or adult life. Male sexual activity and learning capacity were permanently decreased in neonatally pargyline- or reserpine-treated animals, but permanently increased in neonatally pyridostigmine-treated rats. These findings suggest that nonphysiological concentrations and/or turnover rates of neurotransmitters, if produced during a critical period of brain differentiation, are able to induce lifelond effective behavioural changes, i.e. teratopsychogenetic effects."}
{"id": "PMID:11993", "title": "[Plasma testosterone values in patients with somatosexual development disturbances from 11 years old to adulthood].", "content": "The testosterone plasma level was determined in 5 groups: 1. in 69 normal juveniles and 85 fertile males at the age of 11 to 45 years, 2. in 42 patients with hypospadia or epispadia aged 11 to 25 years, 3. in 72 males with unilateral cryptorchidism at the age of 11 to 45 years, 4. in 83 males with bilateral cryptorchidism aged 11 to 45 years and 5. in 106 patients with Klinefelter's syndrome at the age of 16 to 45 years. A pubertal increase of the testosterone plasma level was found to begin in subjects with cryptorchidism or Klinefelter's syndrome at a similar age as in the control group. However, as early as at the age of 13 to 14 years decreased testosterone values were found in the patients as compared to normal juveniles. Between 19 and 20 years, the plasma testosterone level was significantly decreased in all patient-groups as compared to the controls of similar age. In adulthood, plasma testosterone concentrations in the patient groups were observed to be 4 to 6 ng/ml without significant age-dependent changes, which are characteristic of normospermic males. Different degrees of clinical symptoms indicating androgen deficiency found in various patient groups despite similar androgen levels in adulthood suggest a different responsiveness of their target organs to androgens.", "contents": "[Plasma testosterone values in patients with somatosexual development disturbances from 11 years old to adulthood]. The testosterone plasma level was determined in 5 groups: 1. in 69 normal juveniles and 85 fertile males at the age of 11 to 45 years, 2. in 42 patients with hypospadia or epispadia aged 11 to 25 years, 3. in 72 males with unilateral cryptorchidism at the age of 11 to 45 years, 4. in 83 males with bilateral cryptorchidism aged 11 to 45 years and 5. in 106 patients with Klinefelter's syndrome at the age of 16 to 45 years. A pubertal increase of the testosterone plasma level was found to begin in subjects with cryptorchidism or Klinefelter's syndrome at a similar age as in the control group. However, as early as at the age of 13 to 14 years decreased testosterone values were found in the patients as compared to normal juveniles. Between 19 and 20 years, the plasma testosterone level was significantly decreased in all patient-groups as compared to the controls of similar age. In adulthood, plasma testosterone concentrations in the patient groups were observed to be 4 to 6 ng/ml without significant age-dependent changes, which are characteristic of normospermic males. Different degrees of clinical symptoms indicating androgen deficiency found in various patient groups despite similar androgen levels in adulthood suggest a different responsiveness of their target organs to androgens."}
{"id": "PMID:11995", "title": "In vivo measurements of oxyhaemoglobin saturation by a fiberoptic catheter. The effects of variations in pH and haematocrit.", "content": "The development of plastic fiberoptic catheters, cheaper and less fragile than glass ones, has enabled the more widespread use of oxyhaemoglobin saturation (SO2) monitoring. They allow direct determinations of SO2 to be made, using reflection spectrophotometry. The purpose of the present work was to evaluate the accuracy of SO2 measurements as provided by these catheters. The studies were performed in dogs, with large variations of SO2, acid-base balance and haematocrit levels.", "contents": "In vivo measurements of oxyhaemoglobin saturation by a fiberoptic catheter. The effects of variations in pH and haematocrit. The development of plastic fiberoptic catheters, cheaper and less fragile than glass ones, has enabled the more widespread use of oxyhaemoglobin saturation (SO2) monitoring. They allow direct determinations of SO2 to be made, using reflection spectrophotometry. The purpose of the present work was to evaluate the accuracy of SO2 measurements as provided by these catheters. The studies were performed in dogs, with large variations of SO2, acid-base balance and haematocrit levels."}
{"id": "PMID:11996", "title": "The action of bombesin on gastric secretion of the chicken.", "content": "The natural tetradecapeptide bombesin at a threshold dose of 3--5 ng/kg/min i.v. stimulates gastric secretion in the chicken with either an acute or a chronic proventriculus fistula; this effect is blocked by atropine. The occurrence of tachyphylaxis in the acute, but not in the chronic preparation, and the inhibition of the response by proventriculus acidification, in the presence of an intact sensitivity to caerulein -- a directly stimulating agent -- support the hypothesis of an indirect mechanism of action of bombesin, namely the release of endogenous gastrin, as well as of the existence of gastrin also in the chicken.", "contents": "The action of bombesin on gastric secretion of the chicken. The natural tetradecapeptide bombesin at a threshold dose of 3--5 ng/kg/min i.v. stimulates gastric secretion in the chicken with either an acute or a chronic proventriculus fistula; this effect is blocked by atropine. The occurrence of tachyphylaxis in the acute, but not in the chronic preparation, and the inhibition of the response by proventriculus acidification, in the presence of an intact sensitivity to caerulein -- a directly stimulating agent -- support the hypothesis of an indirect mechanism of action of bombesin, namely the release of endogenous gastrin, as well as of the existence of gastrin also in the chicken."}
{"id": "PMID:11997", "title": "Further evidence implicating E-type prostaglandins in the patency of the lamb ductus arteriosus.", "content": "A blocker of prostaglandin (PG) snythesis, indomethacin, given to pregnant ewes near term produces constriction of the lamb ductus arteriosus in utero. The result supports the hypothesis formulated previously that E-type prostaglandins, which are potent relaxant on the ductus, are responsible for maintaining the patency of the vessel during foetal life.", "contents": "Further evidence implicating E-type prostaglandins in the patency of the lamb ductus arteriosus. A blocker of prostaglandin (PG) snythesis, indomethacin, given to pregnant ewes near term produces constriction of the lamb ductus arteriosus in utero. The result supports the hypothesis formulated previously that E-type prostaglandins, which are potent relaxant on the ductus, are responsible for maintaining the patency of the vessel during foetal life."}
{"id": "PMID:11998", "title": "A comparison of the actions of ICI66082 and propranolol on cardiac and peripheral beta-adrenoceptors.", "content": "The relative blocking potencies of ICI66082 and propranolol with respect to heart rate contractility, diastolic blood pressure and peripheral vascular conductance were compared in anaesthetized dogs. Peripheral blood flow was measured with an electromagnetic flow-probe around the descending aorta with retrograde cannulation of the inferior mesenteric artery for intra-arterial injections of isoprenaline. Cardiac and peripheral vascular effects of ICI66082 and propranolol were compared in terms of the shifts in the dose--response curves after i.v. and intra-arterial injections of isoprenaline. Propranolol was twice as potent as an equimolar dose of ICI66082 on cardiac beta-adrenoceptors. It was 70--130 times more potent in its action on the peripheral vascular receptors. Propranolol itself was 3 times more potent in blocking peripheral vascular receptors than cardiac beta-receptors. ICI66082 was 17--21 times more active in blocking the myocardial beta-adrenoceptors than those in the peripheral vessels. Electrophysiological studies showed that ICI66082 is devoid of membrane-depressant properties in concentrations up to 100 mg/l.", "contents": "A comparison of the actions of ICI66082 and propranolol on cardiac and peripheral beta-adrenoceptors. The relative blocking potencies of ICI66082 and propranolol with respect to heart rate contractility, diastolic blood pressure and peripheral vascular conductance were compared in anaesthetized dogs. Peripheral blood flow was measured with an electromagnetic flow-probe around the descending aorta with retrograde cannulation of the inferior mesenteric artery for intra-arterial injections of isoprenaline. Cardiac and peripheral vascular effects of ICI66082 and propranolol were compared in terms of the shifts in the dose--response curves after i.v. and intra-arterial injections of isoprenaline. Propranolol was twice as potent as an equimolar dose of ICI66082 on cardiac beta-adrenoceptors. It was 70--130 times more potent in its action on the peripheral vascular receptors. Propranolol itself was 3 times more potent in blocking peripheral vascular receptors than cardiac beta-receptors. ICI66082 was 17--21 times more active in blocking the myocardial beta-adrenoceptors than those in the peripheral vessels. Electrophysiological studies showed that ICI66082 is devoid of membrane-depressant properties in concentrations up to 100 mg/l."}
{"id": "PMID:11999", "title": "Effect of propranolol on antinociceptive, tolerance- and dependence-producing properties of morphine in rodents and monkeys.", "content": "Since an abstinence syndrome may accompany the injection of opioids in addicts pretreated with propranolol the morphine antagonistic properties of this compound were investigated. Racemic propranolol did not significantly affect the antinociceptive ED50 of morphine in rodents and neither precipitated abstinence in morphine-dependent monkeys nor exacerbated the syndrome in 24 hr withdrawn monkeys. Multiple doses of propranolol did not alter the development of physical dependence on morphine in monkeys. Clinical narcotic antagonism would not be predicted from this profile. Evidence for a possible propranolol-morphine interaction came from studies using the mouse tail flick test. Thus, after 8 injections of propranolol (over 4 days) mice were tolerant to normally effective doses of morphine. Concurrent injections of naloxone antagonised this effect. When propranolol and morphine were administered concurrently the morphine ED50 (on day 5) was twice that of the group receiving morphine alone. Similar results were obtained with d-propranolol; practolol had a neutral effect.", "contents": "Effect of propranolol on antinociceptive, tolerance- and dependence-producing properties of morphine in rodents and monkeys. Since an abstinence syndrome may accompany the injection of opioids in addicts pretreated with propranolol the morphine antagonistic properties of this compound were investigated. Racemic propranolol did not significantly affect the antinociceptive ED50 of morphine in rodents and neither precipitated abstinence in morphine-dependent monkeys nor exacerbated the syndrome in 24 hr withdrawn monkeys. Multiple doses of propranolol did not alter the development of physical dependence on morphine in monkeys. Clinical narcotic antagonism would not be predicted from this profile. Evidence for a possible propranolol-morphine interaction came from studies using the mouse tail flick test. Thus, after 8 injections of propranolol (over 4 days) mice were tolerant to normally effective doses of morphine. Concurrent injections of naloxone antagonised this effect. When propranolol and morphine were administered concurrently the morphine ED50 (on day 5) was twice that of the group receiving morphine alone. Similar results were obtained with d-propranolol; practolol had a neutral effect."}
{"id": "PMID:12000", "title": "Separate receptors mediating the positive inotropic and chronotropic effect of histamine in guinea-pig atria.", "content": "The direct positive inotropic effect of histamine was studied on paced left atrial preparation from guinea pigs. Histamine (10(-8) to 10(-4) M) increased the maximum tension developed in left atria incubated at 35degreesC and driven at 2 Hz. The maximum increase in tension was 60% of that observed with norepinephrine. Metiamide (3 X 10(-5) M, a specific H2-receptor antagonist) did not alter the inotropic response of left atria to histamine. However, tripelennamine (a typical H1-receptor antagonist) competitively shifted the histamine inotropic dose--response curve to the right at concentrations from 10(-8) to 10(-7) M. Higher concentrations (3 X 10(-7) and 10(-6) M) caused little further additional shift to the right. The positive chronotropic effect of histamine on spontaneously beating atria was competitively antagonized by metiamide (10(-6) and 3 X 10(-6) M). These results demonstrate that in guinea-pig atria histamine increases myocardial contractility by an interaction with receptors closely related to classical H1-receptors while its chronotropic effect is mediated by interaction with H2-receptors.", "contents": "Separate receptors mediating the positive inotropic and chronotropic effect of histamine in guinea-pig atria. The direct positive inotropic effect of histamine was studied on paced left atrial preparation from guinea pigs. Histamine (10(-8) to 10(-4) M) increased the maximum tension developed in left atria incubated at 35degreesC and driven at 2 Hz. The maximum increase in tension was 60% of that observed with norepinephrine. Metiamide (3 X 10(-5) M, a specific H2-receptor antagonist) did not alter the inotropic response of left atria to histamine. However, tripelennamine (a typical H1-receptor antagonist) competitively shifted the histamine inotropic dose--response curve to the right at concentrations from 10(-8) to 10(-7) M. Higher concentrations (3 X 10(-7) and 10(-6) M) caused little further additional shift to the right. The positive chronotropic effect of histamine on spontaneously beating atria was competitively antagonized by metiamide (10(-6) and 3 X 10(-6) M). These results demonstrate that in guinea-pig atria histamine increases myocardial contractility by an interaction with receptors closely related to classical H1-receptors while its chronotropic effect is mediated by interaction with H2-receptors."}
{"id": "PMID:12027", "title": "The effects of altering the pH of seminal fluid on the sex ratio of rabbit offspring.", "content": "It has been suggested that the pH of the vagina at the time of fertilization may have a differential effect on X- or Y-bearing sperm and thereby affect the sex of the offspring. To test this postulate, rabbit semen was collected, diluted 1:10 with a buffer of pH 5.4, 6.9, or 9.6, and after 20 minutes 0.5 ml of semen-buffer mixture was used for insemination in an ovulation-induced female. Newborn pups were examined both externally and internally for gender. The females inseminated with acidic semen had 6 litters, 50 offspring, with 48% males; those with neutral semen had 8 litters, 48 offspring, with 63% males; and those with alkaline semen had 7 litters, 49 offspring, with 49% males. There was no significant difference in these sex ratios from the expected 50% males. Motility of rabbit sperm at 23 degrees C in buffers of pH 4.6, 5.4, 6.9, 9.6, and 9.8 was reduced in vitro as the pH deviated from neutrality. Acid conditions were more detrimental than alkaline conditions. Sperm lost their motility more quickly in buffers of 37 degrees C than in buffers of 23 degrees C. It was not possible with scanning electron microscopy to distinguish morphologically between X- and Y-bearing sperm. It seems unlikely that a direct effect of pH on sperm can be a single influence on the sex of offspring.", "contents": "The effects of altering the pH of seminal fluid on the sex ratio of rabbit offspring. It has been suggested that the pH of the vagina at the time of fertilization may have a differential effect on X- or Y-bearing sperm and thereby affect the sex of the offspring. To test this postulate, rabbit semen was collected, diluted 1:10 with a buffer of pH 5.4, 6.9, or 9.6, and after 20 minutes 0.5 ml of semen-buffer mixture was used for insemination in an ovulation-induced female. Newborn pups were examined both externally and internally for gender. The females inseminated with acidic semen had 6 litters, 50 offspring, with 48% males; those with neutral semen had 8 litters, 48 offspring, with 63% males; and those with alkaline semen had 7 litters, 49 offspring, with 49% males. There was no significant difference in these sex ratios from the expected 50% males. Motility of rabbit sperm at 23 degrees C in buffers of pH 4.6, 5.4, 6.9, 9.6, and 9.8 was reduced in vitro as the pH deviated from neutrality. Acid conditions were more detrimental than alkaline conditions. Sperm lost their motility more quickly in buffers of 37 degrees C than in buffers of 23 degrees C. It was not possible with scanning electron microscopy to distinguish morphologically between X- and Y-bearing sperm. It seems unlikely that a direct effect of pH on sperm can be a single influence on the sex of offspring."}
{"id": "PMID:12062", "title": "Properties of prostaglandin F2alpha receptors in bovine corpus luteum cell membranes.", "content": "The specific binding of 3H-labeled prostaglandin (PG) F2alpha to bovine corpus luteum cell membranes was a rapid (K1=1.1 X 10(4) M(-1)S(-1) and reversible (K(-1)=3.3 X 10(-4) S(-1)) process at 22 degrees C. The specific binding was also a saturable process exhibiting two classes of receptors with apparent dissociation constants (Kds) of 1.6 X 10(-9) M and 2.4 X 10(-8) M. The heterogenous nature of [3H]PGF2alpha binding does not appear to be due to negative cooperatively but merely to represent the existence of two independent groups of receptor sites with discrete affinities. Free energy changes of +11.9 and +10.3 Kcal/mol were calculated from the Kds of high and low affinity receptors, respectively. The binding of [3H]PGF2alpha to the membranes was not accompanied by any detectable changes in receptor-bound or free [3H]PGF2alpha. Addition of increasing amounts of unlabeled PGF2alpha resulted in a dose-dependent inhibition of [3H]PGF2alpha binding to the membranes, with complete inhibition occurring at 10(-6) M. Other unlabeled PGs such as PGF1alpha, PGE2 (5-fold), PGE1 (120-fold), PGA1 and PGB1 (about 10,000-fold) were less effective when compared to unlabeled PGF2alpha in inhibiting [3H] PGF2alpha binding to the membranes. The metabolites of PGF2alpha, 15-keto-PGF2alpha and 13,14-dihydro-15-keto-PGF2alpha had 100-fold less affinity for PGF2alpha receptors. 15(S)15-Methyl-PGF2alpha, an analogue of PGF2alpha, had a fairly high affinity but lower than its parent molecule. Various unsaturated fatty acids, indomethacin and 7-oxa-13-prostynoic acid had 3,000- to 10,000-fold less affinities for PGF2alpha receptors. Incubation of membranes with various enzymes revealed that PGF2alpha receptor molecules are protein in nature which require membrane lipids and specific phospholipids for binding function. Among the various phospholipids used, sphingomyelin was found to be very effective in restoring the loss of [3H]PGF2alpha binding in phospholipase C-treated membranes. N-Ethylmaleimide, but not other SH group alkylating agents inhibited binding. The binding was also inhibited by tetranitromethane, dinitrofluorobenzene and acetic anhydride. This suggested that tyrosyl, histidyl, tryptophan and amino (any one or all of them) but not SH groups were involved in binding interaction.", "contents": "Properties of prostaglandin F2alpha receptors in bovine corpus luteum cell membranes. The specific binding of 3H-labeled prostaglandin (PG) F2alpha to bovine corpus luteum cell membranes was a rapid (K1=1.1 X 10(4) M(-1)S(-1) and reversible (K(-1)=3.3 X 10(-4) S(-1)) process at 22 degrees C. The specific binding was also a saturable process exhibiting two classes of receptors with apparent dissociation constants (Kds) of 1.6 X 10(-9) M and 2.4 X 10(-8) M. The heterogenous nature of [3H]PGF2alpha binding does not appear to be due to negative cooperatively but merely to represent the existence of two independent groups of receptor sites with discrete affinities. Free energy changes of +11.9 and +10.3 Kcal/mol were calculated from the Kds of high and low affinity receptors, respectively. The binding of [3H]PGF2alpha to the membranes was not accompanied by any detectable changes in receptor-bound or free [3H]PGF2alpha. Addition of increasing amounts of unlabeled PGF2alpha resulted in a dose-dependent inhibition of [3H]PGF2alpha binding to the membranes, with complete inhibition occurring at 10(-6) M. Other unlabeled PGs such as PGF1alpha, PGE2 (5-fold), PGE1 (120-fold), PGA1 and PGB1 (about 10,000-fold) were less effective when compared to unlabeled PGF2alpha in inhibiting [3H] PGF2alpha binding to the membranes. The metabolites of PGF2alpha, 15-keto-PGF2alpha and 13,14-dihydro-15-keto-PGF2alpha had 100-fold less affinity for PGF2alpha receptors. 15(S)15-Methyl-PGF2alpha, an analogue of PGF2alpha, had a fairly high affinity but lower than its parent molecule. Various unsaturated fatty acids, indomethacin and 7-oxa-13-prostynoic acid had 3,000- to 10,000-fold less affinities for PGF2alpha receptors. Incubation of membranes with various enzymes revealed that PGF2alpha receptor molecules are protein in nature which require membrane lipids and specific phospholipids for binding function. Among the various phospholipids used, sphingomyelin was found to be very effective in restoring the loss of [3H]PGF2alpha binding in phospholipase C-treated membranes. N-Ethylmaleimide, but not other SH group alkylating agents inhibited binding. The binding was also inhibited by tetranitromethane, dinitrofluorobenzene and acetic anhydride. This suggested that tyrosyl, histidyl, tryptophan and amino (any one or all of them) but not SH groups were involved in binding interaction."}
{"id": "PMID:12063", "title": "Isozyme patterns of branched-chain amino acid transminase in cultured Morris hepatoma 7316A.", "content": "Cultured cells from Morris hepatoma 7316A contained isozymes I and II, but not isozyme III, of branched-chain amino acid transaminase. They also contained tyrosine transaminase. Isozyme II and tyrosine transaminase were induced by addition of cortisol. These findings agree well with in vivo findings. However, prolonged culutre of the cells for over 500 days caused deviation of the chromosomal bumber and activity of both enzymes, and they were no longer affected by cortisol. A tumor formed by back-transplantation of the cells showed the typical isozyme pattern of rapidly growing hepatomas, such as Yoshida ascites hepatomas, i.e., isozymes I and III. These results were discussed in relation to change of gene expression during culture.", "contents": "Isozyme patterns of branched-chain amino acid transminase in cultured Morris hepatoma 7316A. Cultured cells from Morris hepatoma 7316A contained isozymes I and II, but not isozyme III, of branched-chain amino acid transaminase. They also contained tyrosine transaminase. Isozyme II and tyrosine transaminase were induced by addition of cortisol. These findings agree well with in vivo findings. However, prolonged culutre of the cells for over 500 days caused deviation of the chromosomal bumber and activity of both enzymes, and they were no longer affected by cortisol. A tumor formed by back-transplantation of the cells showed the typical isozyme pattern of rapidly growing hepatomas, such as Yoshida ascites hepatomas, i.e., isozymes I and III. These results were discussed in relation to change of gene expression during culture."}
{"id": "PMID:12064", "title": "Serum gamma-glutamyl transpeptidase activity in viral hepatitis: suppression in pregnancy and by birth control pills.", "content": "gamma-Glutamyl transpeptidase (GGT) activity in serum was increased in the majority of women with viral hepatitis occurring in the first half of pregnancy. By contrast, GGT activity was abnormal less frequently and the mean value was relatively depressed, even though hepatitis was as severe, in the second half of gestation. Mean GGT activity was also lower, and abnormal values were less frequent, in nonpregnant women with viral hepatitis who were taking birth control pills (BCP). Depressed GGT is not attributable to an inhibitor in serum in women in late pregnancy or taking BCP. The data suggest that estrogen and/or progestational compounds affect liver such that less GGT is released into blood with acute hepatocellular injury. In addition, hyperbilirubinemia was found to be associated with depressed serum GGT activity, and bilirubin added to serum in vitro interfered with measured activity of the enzyme.", "contents": "Serum gamma-glutamyl transpeptidase activity in viral hepatitis: suppression in pregnancy and by birth control pills. gamma-Glutamyl transpeptidase (GGT) activity in serum was increased in the majority of women with viral hepatitis occurring in the first half of pregnancy. By contrast, GGT activity was abnormal less frequently and the mean value was relatively depressed, even though hepatitis was as severe, in the second half of gestation. Mean GGT activity was also lower, and abnormal values were less frequent, in nonpregnant women with viral hepatitis who were taking birth control pills (BCP). Depressed GGT is not attributable to an inhibitor in serum in women in late pregnancy or taking BCP. The data suggest that estrogen and/or progestational compounds affect liver such that less GGT is released into blood with acute hepatocellular injury. In addition, hyperbilirubinemia was found to be associated with depressed serum GGT activity, and bilirubin added to serum in vitro interfered with measured activity of the enzyme."}
{"id": "PMID:12065", "title": "[Effect of O-methylhydroxylamine on extracellular phage cd].", "content": "Study was made of lethal and mutagenic effect of 1 M and 0,5 M O-methylhydroxylamine (OMHA) on extracellular phage Sd. The correlation between chemical changes of the genome and the degree of phage inactivation under the action of OMHA has been established within the range of studied pH (4,5-7,0) of the reaction medium. OMHA in activates the phage at the highest rate at pH 5,0, which agrees with chemical data indicating that the total rate of OMHA modification of cytidine units is maximal at this pH. Inactivation curves of OMHA-treated phage are single-hit at pH investigated, but have a small initial shoulder; at pH 5,0 and 4,5 inactivation curves consist of two exponents, the second exponent having the smallest slope, that is the phage is characterized by an increased resistance to OMHA at this section. The increased phage resistance can be explained by transforming the original product IV (cross-linked with protein) into the product II (N4-methoxy-6-methoxyamine-5,6-dihydrocytidine) which can be repaired in contrast to IV. OMHA has a high mutagenic effect on phage Sd. Under optimal conditions (at pH 4,5) the mutagen induces plaque mutants (up to 6%) among survived phages. The data obtained correlate with the fact that with decreasing pH (from 5,0 to 4,5) the ratio of the \"mutagen\" unit - N4-methoxycytidine (product III) to the \"inactivating\" one (product II) increases. The curves of mutation induction under the action of OMHA have a characteristic form with the initial linear section and the maximum or the plateau similar to mutation curves to be observed under the action of radiation and chemical agents.", "contents": "[Effect of O-methylhydroxylamine on extracellular phage cd]. Study was made of lethal and mutagenic effect of 1 M and 0,5 M O-methylhydroxylamine (OMHA) on extracellular phage Sd. The correlation between chemical changes of the genome and the degree of phage inactivation under the action of OMHA has been established within the range of studied pH (4,5-7,0) of the reaction medium. OMHA in activates the phage at the highest rate at pH 5,0, which agrees with chemical data indicating that the total rate of OMHA modification of cytidine units is maximal at this pH. Inactivation curves of OMHA-treated phage are single-hit at pH investigated, but have a small initial shoulder; at pH 5,0 and 4,5 inactivation curves consist of two exponents, the second exponent having the smallest slope, that is the phage is characterized by an increased resistance to OMHA at this section. The increased phage resistance can be explained by transforming the original product IV (cross-linked with protein) into the product II (N4-methoxy-6-methoxyamine-5,6-dihydrocytidine) which can be repaired in contrast to IV. OMHA has a high mutagenic effect on phage Sd. Under optimal conditions (at pH 4,5) the mutagen induces plaque mutants (up to 6%) among survived phages. The data obtained correlate with the fact that with decreasing pH (from 5,0 to 4,5) the ratio of the \"mutagen\" unit - N4-methoxycytidine (product III) to the \"inactivating\" one (product II) increases. The curves of mutation induction under the action of OMHA have a characteristic form with the initial linear section and the maximum or the plateau similar to mutation curves to be observed under the action of radiation and chemical agents."}
{"id": "PMID:12067", "title": "Blood pH: a test for assessment of severity in proctocolitis.", "content": "Acid base balance was studied in 58 patients with active idiopathic proctocolitis; the condition of 10 of them was complicated by toxic megacolon. Arterial blood pH increased progressively with increased severity of the colitis and as the lesions became more widespread. Statistically significant differences were observed in pH values between the mild/moderate and severe forms and between the severe and complicated forms ('toxic megacolon'). A linear correlation was found between pH and the amount of intestinal gas, pulse rate, and plasma albumin.", "contents": "Blood pH: a test for assessment of severity in proctocolitis. Acid base balance was studied in 58 patients with active idiopathic proctocolitis; the condition of 10 of them was complicated by toxic megacolon. Arterial blood pH increased progressively with increased severity of the colitis and as the lesions became more widespread. Statistically significant differences were observed in pH values between the mild/moderate and severe forms and between the severe and complicated forms ('toxic megacolon'). A linear correlation was found between pH and the amount of intestinal gas, pulse rate, and plasma albumin."}
{"id": "PMID:12068", "title": "Relationships between mucosal hydrolysis and transport of two phenylalanine dipeptides.", "content": "In order to investigate the source of free amino acids found in the gut lumen during absorption of dipeptides, as well as evaluating the role of brush border peptidases in the mucosal hydrolysis of dipeptides during absorption, rates of dipeptide disappearance and appearance of hydrolytic products were measured during perfusion of rat jejunum and ileum in vivo with buffered and unbuffered 10 mM solutions of glycl-L-phenylalanine (Gly-Phe) and L-phenylalanyl-glycine (Phe-Gly). Mucosal brush border peptidase activity was then measured in the perfused segments in vitro at luminal pH and at two substrate concentrations. In addition cytosol peptidase activity in the perfused segments was measured at pH 7-4 and at 10 mM substrate concentrations. In the jejunum, there was a relationship between rates of free phenylalanine appearance in vivo (Phe-Gly greater than Gly-Phe) and rates of brush border (Phe-Gly greater than Gly-Phe) rather than cytosol (Gly-Phe greater than Phe-Gly) peptidase activities. No constant relationship between free phenylalanine appearance and hydrolysis of the dipeptides by either brush border or cytosol peptidases was observed in the ileal studies. These findings suggest that, in the jejunum, hydrolytic products originate from the surface of the cell whereas, in the ileum, hydrolytic products originate from both the intracellular compartment as well as from the surface of the mucosal cell. In the jejunum, in vitro rates of brush border hydrolysis of Gly-Phe were always less than in vivo disappearance rates, whereas rates of Phe-Gly brush border hydrolysis always exceeded luminal disappearance rates. These data imply that Gly-Phe is predominantly transported intact and hydrolysed by cytosol peptidases, In contrast, brush border peptidases play an importnat role in the mucosal hydrolysis of Phe-Gly.", "contents": "Relationships between mucosal hydrolysis and transport of two phenylalanine dipeptides. In order to investigate the source of free amino acids found in the gut lumen during absorption of dipeptides, as well as evaluating the role of brush border peptidases in the mucosal hydrolysis of dipeptides during absorption, rates of dipeptide disappearance and appearance of hydrolytic products were measured during perfusion of rat jejunum and ileum in vivo with buffered and unbuffered 10 mM solutions of glycl-L-phenylalanine (Gly-Phe) and L-phenylalanyl-glycine (Phe-Gly). Mucosal brush border peptidase activity was then measured in the perfused segments in vitro at luminal pH and at two substrate concentrations. In addition cytosol peptidase activity in the perfused segments was measured at pH 7-4 and at 10 mM substrate concentrations. In the jejunum, there was a relationship between rates of free phenylalanine appearance in vivo (Phe-Gly greater than Gly-Phe) and rates of brush border (Phe-Gly greater than Gly-Phe) rather than cytosol (Gly-Phe greater than Phe-Gly) peptidase activities. No constant relationship between free phenylalanine appearance and hydrolysis of the dipeptides by either brush border or cytosol peptidases was observed in the ileal studies. These findings suggest that, in the jejunum, hydrolytic products originate from the surface of the cell whereas, in the ileum, hydrolytic products originate from both the intracellular compartment as well as from the surface of the mucosal cell. In the jejunum, in vitro rates of brush border hydrolysis of Gly-Phe were always less than in vivo disappearance rates, whereas rates of Phe-Gly brush border hydrolysis always exceeded luminal disappearance rates. These data imply that Gly-Phe is predominantly transported intact and hydrolysed by cytosol peptidases, In contrast, brush border peptidases play an importnat role in the mucosal hydrolysis of Phe-Gly."}
{"id": "PMID:12069", "title": "Effect of metiamide on basal and stimulated serum cholecystokinin levels in duodenal ulcer patients.", "content": "Serum cholecystokinin (CCK) levels were measured in 10 patients with chronic duodenal ulcers, fasting and at intervals after two standard tests meals  (300 ml of 40 mmol/1 phenylalanine solution), one given before and one during H2-receptor blockade with metiamide (200 mg four times a day). Fasting serum CCK levels were lower in all patients during treatment with metiamide (the mean level falling from 306-0 +/- 102-0 (SEM) to 82-1 +/- 23-6 pg/ml after treatment (p less than 0-01)). In contrast, peak serum CCK levels after the meal were not significantly different (7400 +/- 1141 pg/ml before treatment and 7569 +/- 1293 pg/ml on metiamide). We conclude that in duodenal ulcer patients CCK secretion under basal condtions may be in part dependent on stimulation of the small intestinal mucosa by gastric acid, but that, after an amino acid  meal, gastric acid secretion is less important in determining the amount of CCK released.", "contents": "Effect of metiamide on basal and stimulated serum cholecystokinin levels in duodenal ulcer patients. Serum cholecystokinin (CCK) levels were measured in 10 patients with chronic duodenal ulcers, fasting and at intervals after two standard tests meals  (300 ml of 40 mmol/1 phenylalanine solution), one given before and one during H2-receptor blockade with metiamide (200 mg four times a day). Fasting serum CCK levels were lower in all patients during treatment with metiamide (the mean level falling from 306-0 +/- 102-0 (SEM) to 82-1 +/- 23-6 pg/ml after treatment (p less than 0-01)). In contrast, peak serum CCK levels after the meal were not significantly different (7400 +/- 1141 pg/ml before treatment and 7569 +/- 1293 pg/ml on metiamide). We conclude that in duodenal ulcer patients CCK secretion under basal condtions may be in part dependent on stimulation of the small intestinal mucosa by gastric acid, but that, after an amino acid  meal, gastric acid secretion is less important in determining the amount of CCK released."}
{"id": "PMID:12070", "title": "Reversible norepinephrine binding to rabbit myometrium: relationship to sites of known biological significance.", "content": "Catecholamines bind specifically to several cell types and subcellular fractions. This binding is not consistent with binding to the adrenergic receptor. Catecholamines would be expected to bind to sites other than the adrenergic receptor (uptake 1, uptake 2, nerve vesicles, catecholamine-O-methyl transferase and serum albumin). We characterized the binding of 3H-norepinephrine to microsomes prepared from rabbit myometrium. In the presence of antioxidant binding was reversible and 3H-norepinephrine could be recovered bound to microsomes or free in incubation media. The binding was not characteristic of binding to any one known biological site. It may represent binding to a mixture of these sites or may be fortuitous binding to sites of unknown biological significance.", "contents": "Reversible norepinephrine binding to rabbit myometrium: relationship to sites of known biological significance. Catecholamines bind specifically to several cell types and subcellular fractions. This binding is not consistent with binding to the adrenergic receptor. Catecholamines would be expected to bind to sites other than the adrenergic receptor (uptake 1, uptake 2, nerve vesicles, catecholamine-O-methyl transferase and serum albumin). We characterized the binding of 3H-norepinephrine to microsomes prepared from rabbit myometrium. In the presence of antioxidant binding was reversible and 3H-norepinephrine could be recovered bound to microsomes or free in incubation media. The binding was not characteristic of binding to any one known biological site. It may represent binding to a mixture of these sites or may be fortuitous binding to sites of unknown biological significance."}
{"id": "PMID:12071", "title": "Occurrence of C1 inactivator and other proteinase inhibitors in euglobulin fractions and their influence on fibrinolytic activity.", "content": "Considerable amounts of C1 inactivator and inter-alpha-trypsin inhibitor pecipitate during euglobulin fractionation of human plasma. The amount precipitated depends on the ionic strength and the pH during the fractionation procedure. In contrast, alpha1-anti-trypsin, alpha2-macroglobulinand antithrombin II are present in euglobulin fractions in trace amounts only. The fibrinolytic activity of the euglobulin fractions is inhibited by the endogenous C1 inactivator, particularly as shown by comparison of normal and hereditary angioneurotic edema (HANE) plasma.", "contents": "Occurrence of C1 inactivator and other proteinase inhibitors in euglobulin fractions and their influence on fibrinolytic activity. Considerable amounts of C1 inactivator and inter-alpha-trypsin inhibitor pecipitate during euglobulin fractionation of human plasma. The amount precipitated depends on the ionic strength and the pH during the fractionation procedure. In contrast, alpha1-anti-trypsin, alpha2-macroglobulinand antithrombin II are present in euglobulin fractions in trace amounts only. The fibrinolytic activity of the euglobulin fractions is inhibited by the endogenous C1 inactivator, particularly as shown by comparison of normal and hereditary angioneurotic edema (HANE) plasma."}
{"id": "PMID:12072", "title": "Studies on the dynamics and mechanism of glibenclamide-induced insulin secretion.", "content": "Sustained, 60-minute perfusion of glibenclamide (0.5, 1.5 and 10 mug/ml) elicits a one-phase insulin release profile, formed by a rapid secretion peak followed by a second peak with lower insulin levels than the former. Basal insulin secretion values are observed during the period comprised between 13 and 60 minutes of perfusion. Concurrent stimulation with glucose (100, 150, 200 and 300 mg%) plus glibenclamide (1 mug/ml) causes a marked rise in both phases of insulin secretion. The addition of glibenclamide does not modify the biphasic secretion pattern caused by maximal glucose concentration (400 mg%). The maximal values of both phases of secretion in the dose-response curve elicited by different glucose concentrations shift to the left when glibenclamide is added to the perfusate. The increase in insulin secretion caused by glibenclamide is not inhibited by puromycin. Both theophylline and phentolamine modify and increase the glibenclamide-induced insulin release pattern. Propranolol and imidazole inhibit glibenclamide-induced insulin release. Our results suggest that: 1. Glibenclamide increases beta cell sensitivity to glucose stimulation. 2. Glibenclamide and glucose induce secretion of insulin originating in the same compartment. 3. Modification of alpha and beta adrenergic receptors may modify glibodulate the beta cell response to glibenclamide.", "contents": "Studies on the dynamics and mechanism of glibenclamide-induced insulin secretion. Sustained, 60-minute perfusion of glibenclamide (0.5, 1.5 and 10 mug/ml) elicits a one-phase insulin release profile, formed by a rapid secretion peak followed by a second peak with lower insulin levels than the former. Basal insulin secretion values are observed during the period comprised between 13 and 60 minutes of perfusion. Concurrent stimulation with glucose (100, 150, 200 and 300 mg%) plus glibenclamide (1 mug/ml) causes a marked rise in both phases of insulin secretion. The addition of glibenclamide does not modify the biphasic secretion pattern caused by maximal glucose concentration (400 mg%). The maximal values of both phases of secretion in the dose-response curve elicited by different glucose concentrations shift to the left when glibenclamide is added to the perfusate. The increase in insulin secretion caused by glibenclamide is not inhibited by puromycin. Both theophylline and phentolamine modify and increase the glibenclamide-induced insulin release pattern. Propranolol and imidazole inhibit glibenclamide-induced insulin release. Our results suggest that: 1. Glibenclamide increases beta cell sensitivity to glucose stimulation. 2. Glibenclamide and glucose induce secretion of insulin originating in the same compartment. 3. Modification of alpha and beta adrenergic receptors may modify glibodulate the beta cell response to glibenclamide."}
{"id": "PMID:12073", "title": "Plasma testosterone in prepubertal cryptorchid boys under long-term HCG therapy.", "content": "Plasma testosterone concentrations were determined before and after 6 weeks of human chorionic gonadotropin treatment in 36 prepubertal boys with bilateral or unilateral cryptorchidism. Mean +/- SD basal and post-treatment values (ng/100 ml) in the bilateral group were: treatment successful (n = 14): 32 +/- 19 and 302 +/- 49, treatment unsuccessful (n = 12): 20 +/- 15 and 176 +/- 73. The figures for the unilateral group were: treatment successful (n = 6): 23 +/- 9 and 244 +/- 41, treatment unsuccessful (n = 5): 22 +/- 11 and 264 +/- 102. In the bilateral group significant differences in the T response emerged when successfully treated boys were compared to unsuccessfully treated ones. It is concluded that Leydig cell function may be impaired in some cases of cryptorchidism.", "contents": "Plasma testosterone in prepubertal cryptorchid boys under long-term HCG therapy. Plasma testosterone concentrations were determined before and after 6 weeks of human chorionic gonadotropin treatment in 36 prepubertal boys with bilateral or unilateral cryptorchidism. Mean +/- SD basal and post-treatment values (ng/100 ml) in the bilateral group were: treatment successful (n = 14): 32 +/- 19 and 302 +/- 49, treatment unsuccessful (n = 12): 20 +/- 15 and 176 +/- 73. The figures for the unilateral group were: treatment successful (n = 6): 23 +/- 9 and 244 +/- 41, treatment unsuccessful (n = 5): 22 +/- 11 and 264 +/- 102. In the bilateral group significant differences in the T response emerged when successfully treated boys were compared to unsuccessfully treated ones. It is concluded that Leydig cell function may be impaired in some cases of cryptorchidism."}
{"id": "PMID:12074", "title": "Effects of D-glyceraldehyde and 3-o-methylglucose upon fluorescence of reduced pyridine nucleotides from perifused isolated pancreatic islets.", "content": "In perfused pancreatic islets, the fluorescence of reduced pyridine nucleotides was recorded continuously, D-Glyceraldehyde (5 mM) or 3-o-methylglucose (27.5 mM) never caused a net fluorescence increase. Since stepwise changes of the D-glucose concentration between 0 and 20 mM always induced a fluorescence increase, it is concluded that glucose on the one hand and glyceraldehyde or 3-o-methylglucose on the other hand cause different metabolic states in pancreatic islets.", "contents": "Effects of D-glyceraldehyde and 3-o-methylglucose upon fluorescence of reduced pyridine nucleotides from perifused isolated pancreatic islets. In perfused pancreatic islets, the fluorescence of reduced pyridine nucleotides was recorded continuously, D-Glyceraldehyde (5 mM) or 3-o-methylglucose (27.5 mM) never caused a net fluorescence increase. Since stepwise changes of the D-glucose concentration between 0 and 20 mM always induced a fluorescence increase, it is concluded that glucose on the one hand and glyceraldehyde or 3-o-methylglucose on the other hand cause different metabolic states in pancreatic islets."}
{"id": "PMID:12075", "title": "Peptidase inactivation of hypothalamic releasing hormones.", "content": "With the structural characterization of the hypothalamic hormones, luteinizing hormone-releasing hormone (LH-RH), thyrotrophin-releasing (TRH), melanocyte-stimulating hormone release-inhibiting hormine (MIH), and growth hormone release-inhibiting hormone, (GH-RIH or somatostatin), it has been possible to investigate their enzymic inactivation by peptidases which are present at various sites in the body. Enzymes may play an important part in the control of polypeptide hormone levels and the peptidases acting on these four hypothalamic hormones may regulate the amount of TRH, LH-RH, MIH and somatostatin released from the hypothalamus, or their action at the level of the pituitary and their removal from the circulation. By studying the peptidase enzymes, further information may be obtained on the physiological mechanisms controlling the secretion and actions of hypothalamic hormones, as well as on the design of analogues with increased or competitive activity.", "contents": "Peptidase inactivation of hypothalamic releasing hormones. With the structural characterization of the hypothalamic hormones, luteinizing hormone-releasing hormone (LH-RH), thyrotrophin-releasing (TRH), melanocyte-stimulating hormone release-inhibiting hormine (MIH), and growth hormone release-inhibiting hormone, (GH-RIH or somatostatin), it has been possible to investigate their enzymic inactivation by peptidases which are present at various sites in the body. Enzymes may play an important part in the control of polypeptide hormone levels and the peptidases acting on these four hypothalamic hormones may regulate the amount of TRH, LH-RH, MIH and somatostatin released from the hypothalamus, or their action at the level of the pituitary and their removal from the circulation. By studying the peptidase enzymes, further information may be obtained on the physiological mechanisms controlling the secretion and actions of hypothalamic hormones, as well as on the design of analogues with increased or competitive activity."}
{"id": "PMID:12076", "title": "[The biosynthesis of glutathione in human erythrocytes (author's transl)].", "content": "The concentrations of glutathione precursors in human erythrocytes were investigated. 300muM glutamate, 375 muM glycine, and 10muM cysteine were found by automated amino acid analysis. The concentration of 2-aminobutyrate, the precursor of ophthalmic acid, was 15muM. The influence of the activities of endogenous or added glutamyl-cysteine synthetase and glutathione synthetase on the rate of glutathione biosynthesis was measured in membrane-free hemolysates under physiological conditions. The results show that the rate of the overall biosynthesis mainly depends on the formation of the dipeptide glutamyl-cysteine. The effect of glutathione precursor concentrations on the synthesis of the tripeptide was investigated at constant (endogenous) activities of the synthesizing enzymes. The rate was not enhanced by addition of glutamate and/or glycine unless cysteine or glutamyl-cysteine was also added. It is concluded that the concentration of cysteine limits the actual rate of the glutamyl-cysteine-synthetase reaction in vivo. No cysteine or bis(glutamyl)cystine was detected in human hemolysate; however, these disulfides were converted to glutathione. This indicates that erythrocytes have an appropriate system for their reduction, since the disulfides themselves are not substrates for the glutathione-synthesizing enzymes. Studies with intact human red cells indicate that the uptake of cysteine is the rate-determining step in the biosynthesis of glutathione.", "contents": "[The biosynthesis of glutathione in human erythrocytes (author's transl)]. The concentrations of glutathione precursors in human erythrocytes were investigated. 300muM glutamate, 375 muM glycine, and 10muM cysteine were found by automated amino acid analysis. The concentration of 2-aminobutyrate, the precursor of ophthalmic acid, was 15muM. The influence of the activities of endogenous or added glutamyl-cysteine synthetase and glutathione synthetase on the rate of glutathione biosynthesis was measured in membrane-free hemolysates under physiological conditions. The results show that the rate of the overall biosynthesis mainly depends on the formation of the dipeptide glutamyl-cysteine. The effect of glutathione precursor concentrations on the synthesis of the tripeptide was investigated at constant (endogenous) activities of the synthesizing enzymes. The rate was not enhanced by addition of glutamate and/or glycine unless cysteine or glutamyl-cysteine was also added. It is concluded that the concentration of cysteine limits the actual rate of the glutamyl-cysteine-synthetase reaction in vivo. No cysteine or bis(glutamyl)cystine was detected in human hemolysate; however, these disulfides were converted to glutathione. This indicates that erythrocytes have an appropriate system for their reduction, since the disulfides themselves are not substrates for the glutathione-synthesizing enzymes. Studies with intact human red cells indicate that the uptake of cysteine is the rate-determining step in the biosynthesis of glutathione."}
{"id": "PMID:12077", "title": "[Does a modified gamma-glutamyl cycle exist in human erythrocytes (author's transl)].", "content": "The first step in the biosynthesis of glutathione is the formation of gamma-glutamyl-cysteine by the enzyme glutamyl-cysteine synthetase. Since this enzyme is not specific for cysteine, different gamma-glutamylamino acids may be formed in vivo which represent potential substrates for the enzymes gamma-glutamylcyclotransferase; in this way 5-oxo-L-proline and free amino acid are formed. We investigated in membrane-free hemolysate the competition between the biosynthesis of glutathione or ophthalmic acid and the degradation of gamma-glutamyl peptides by measuring the formation of 5-oxoproline. The endogenous rate of 5-oxoproline production was 0.13 muM/min. This increased to 2muM/min after addition of 2-aminobutyrate, and to 10muM/min after addition of glutamate and 2-aminobutyrate to hemolysate. Addition of cysteine resulted in an increased oxoproline production only under conditions where glutamyl-cysteine accumulated. In addition, it was shown that for glutamyl-2-aminobutyrate the degradation to 5-oxoproline is faster than the utilization for the tripeptide synthesis. This was not the case for glutamyl-cysteine. Since membrane-free hemolysate (which lacks gamma-glutamyltransferase) is able to produce 5-oxoproline starting from glutamate, it is concluded that this 5-oxoprolinent amino acid transport via a modified gamma-glutamyl cycle.", "contents": "[Does a modified gamma-glutamyl cycle exist in human erythrocytes (author's transl)]. The first step in the biosynthesis of glutathione is the formation of gamma-glutamyl-cysteine by the enzyme glutamyl-cysteine synthetase. Since this enzyme is not specific for cysteine, different gamma-glutamylamino acids may be formed in vivo which represent potential substrates for the enzymes gamma-glutamylcyclotransferase; in this way 5-oxo-L-proline and free amino acid are formed. We investigated in membrane-free hemolysate the competition between the biosynthesis of glutathione or ophthalmic acid and the degradation of gamma-glutamyl peptides by measuring the formation of 5-oxoproline. The endogenous rate of 5-oxoproline production was 0.13 muM/min. This increased to 2muM/min after addition of 2-aminobutyrate, and to 10muM/min after addition of glutamate and 2-aminobutyrate to hemolysate. Addition of cysteine resulted in an increased oxoproline production only under conditions where glutamyl-cysteine accumulated. In addition, it was shown that for glutamyl-2-aminobutyrate the degradation to 5-oxoproline is faster than the utilization for the tripeptide synthesis. This was not the case for glutamyl-cysteine. Since membrane-free hemolysate (which lacks gamma-glutamyltransferase) is able to produce 5-oxoproline starting from glutamate, it is concluded that this 5-oxoprolinent amino acid transport via a modified gamma-glutamyl cycle."}
{"id": "PMID:12079", "title": "[Carcinogenic polycyclic aromatic hydrocarbons in petroleum products: possible prevention of mineral oil cancer].", "content": "A real epidemy of cutaneous cancer has appeared from 1954 in a french area specialized in the metal machining industry (valley of the Arve, Haute-Saoie). Two investigations have been carried out: - one, of clinical and epidemiological nature over a period of 15 years, has recorded 133 casesof spinocellular epitheliams often located in the scrotum and has allowed to estimate the hazard for the population of this region at 25 per 100 000 (that is to say 36 times more than for the general population). - the other, of chemical nature, has revealed on one hand that the new cutting oils, such as delivered to the utilizers, rather frequently contain benzo [a] pyrene (concentration : 0,5 to 150 ug/l), and on the other hand that the used oils are inclined to grow richer in carcinogenic hydrocarbons. The prevention must be directed towards a supplementary effort in the refining of industrial oils and proposals for toxicological threshold value, which would allow to supply machine shops with oils no longer presenting a carcinogenic hazards.", "contents": "[Carcinogenic polycyclic aromatic hydrocarbons in petroleum products: possible prevention of mineral oil cancer]. A real epidemy of cutaneous cancer has appeared from 1954 in a french area specialized in the metal machining industry (valley of the Arve, Haute-Saoie). Two investigations have been carried out: - one, of clinical and epidemiological nature over a period of 15 years, has recorded 133 casesof spinocellular epitheliams often located in the scrotum and has allowed to estimate the hazard for the population of this region at 25 per 100 000 (that is to say 36 times more than for the general population). - the other, of chemical nature, has revealed on one hand that the new cutting oils, such as delivered to the utilizers, rather frequently contain benzo [a] pyrene (concentration : 0,5 to 150 ug/l), and on the other hand that the used oils are inclined to grow richer in carcinogenic hydrocarbons. The prevention must be directed towards a supplementary effort in the refining of industrial oils and proposals for toxicological threshold value, which would allow to supply machine shops with oils no longer presenting a carcinogenic hazards."}
{"id": "PMID:12080", "title": "Radiation cancer, safety standards and current levels of exposure.", "content": "Cancer can be induced by radiation in any tissue where cancer occurs naturally. The observation that antenatal diagnostic radiography causes a small but definit increas in childhood cancer is as good evidence as could be expected in support of the scientific expectation that there would be no threshold of dose for carcinogenesis. A linear relation between radiation dose and frequency of of induced cancer is a necessary assumption for a system of radiological protection but is not necessarily a reasonable basis for realistic assessments of cancer risk. Indeed there are radiobiological and epidemiological reasons to the contrary. If the linear hypothesis is accepted then at the present time in the UK the routine practice of medicine is of about 2 orders of magnitude more important in causing cancer than environmental pollution by discharge of radio-activity. The acceptability of radiation safety standards for occupational exposure may be justified by comparison of radiation cancer risks with risks from fatal accidents in the safer industries. The acceptability of the corresponding standards for members of the public seems to require more public discussion of the concept of negligible risk. Emotional reactions to uncontrolled releases of radio-activity are based at least in part on a failure to appreciate the hypothesis of linearity.", "contents": "Radiation cancer, safety standards and current levels of exposure. Cancer can be induced by radiation in any tissue where cancer occurs naturally. The observation that antenatal diagnostic radiography causes a small but definit increas in childhood cancer is as good evidence as could be expected in support of the scientific expectation that there would be no threshold of dose for carcinogenesis. A linear relation between radiation dose and frequency of of induced cancer is a necessary assumption for a system of radiological protection but is not necessarily a reasonable basis for realistic assessments of cancer risk. Indeed there are radiobiological and epidemiological reasons to the contrary. If the linear hypothesis is accepted then at the present time in the UK the routine practice of medicine is of about 2 orders of magnitude more important in causing cancer than environmental pollution by discharge of radio-activity. The acceptability of radiation safety standards for occupational exposure may be justified by comparison of radiation cancer risks with risks from fatal accidents in the safer industries. The acceptability of the corresponding standards for members of the public seems to require more public discussion of the concept of negligible risk. Emotional reactions to uncontrolled releases of radio-activity are based at least in part on a failure to appreciate the hypothesis of linearity."}
{"id": "PMID:12081", "title": "[Epidemiological aspects in carcinogenic risk evaluation arising from pollution].", "content": "Descriptive epidemiology in which population groups are studied can be of considerable value in drawing attention to a potential carcinogen. This must be followed by analytical studies which might either lead with a fair degree of certainty to the identification of the responsible factor or at least help to identify the high-risk group who could then be screened for the suspected cancer. Such epidemiological research must always take into account the results of experimental studies.", "contents": "[Epidemiological aspects in carcinogenic risk evaluation arising from pollution]. Descriptive epidemiology in which population groups are studied can be of considerable value in drawing attention to a potential carcinogen. This must be followed by analytical studies which might either lead with a fair degree of certainty to the identification of the responsible factor or at least help to identify the high-risk group who could then be screened for the suspected cancer. Such epidemiological research must always take into account the results of experimental studies."}
{"id": "PMID:12084", "title": "Effect of thiocyanate on nitrite estimation and the cleavage of nitrosamines.", "content": "Thiocyanate or bromide increased the colour formed by nitrite reacting with sulfanilic acid and naphthylethylenediamine. If the colour reagents were added together with thiocyanate (final concentration, M/10), the colour intensity was doubled. If sulfanilic acid was added three minutes before addition of naphthylethylenediamine, the relationship between nitrite concentration and colour production was more linear in the presence of thiocyanate. This effect was due to thiocyanate catalysing the diazotization of sulfanilic acid and inhibiting the reaction of nitrite with naphthylethylenediamine. Bromide and thiocyanate are similar in their catalytic effects on nitrosation, and hydrobromic acid in glacial acetic acid is an effective reagent for denitrosation of nitrosamine. Although thiocyanate catalysed denitrosation of nitrosamines, the effect was small except with nitrosomethylaniline, which had also been found to be denitrosated by sulfanilic acid. Thiocyanate could not be used generally for the destruction of nitrosamines; it was also found to be ineffective as an alternative to hydrobromic acid in the estimation of nitrosamines.", "contents": "Effect of thiocyanate on nitrite estimation and the cleavage of nitrosamines. Thiocyanate or bromide increased the colour formed by nitrite reacting with sulfanilic acid and naphthylethylenediamine. If the colour reagents were added together with thiocyanate (final concentration, M/10), the colour intensity was doubled. If sulfanilic acid was added three minutes before addition of naphthylethylenediamine, the relationship between nitrite concentration and colour production was more linear in the presence of thiocyanate. This effect was due to thiocyanate catalysing the diazotization of sulfanilic acid and inhibiting the reaction of nitrite with naphthylethylenediamine. Bromide and thiocyanate are similar in their catalytic effects on nitrosation, and hydrobromic acid in glacial acetic acid is an effective reagent for denitrosation of nitrosamine. Although thiocyanate catalysed denitrosation of nitrosamines, the effect was small except with nitrosomethylaniline, which had also been found to be denitrosated by sulfanilic acid. Thiocyanate could not be used generally for the destruction of nitrosamines; it was also found to be ineffective as an alternative to hydrobromic acid in the estimation of nitrosamines."}
{"id": "PMID:12085", "title": "Effects of gallic acid and of ethanol on formation of nitrosodiethylamine.", "content": "In vitro experiments demonstrate that the polyphenol, gallic acid, can both catalyse and inhibit NDEA formation. The products of reaction depend considerably on pH conditions and relative concentrations of the reactants. Therefore, interpretation of in vitro experiments in terms of possible in vivo effects in a given population must take into consideration detailed information on eating and drinking habits which might affect pH conditions and relative concentrations of the reactants in the digestive tract. In this respect, it is interesting to note that epidemiological studies conducted by the agency (Day 1) indicate that tea, which contains gallotannins, is consumed more frequently but in a more diluted brew in the area of high oesophageal cancer incidence of the Caspian littoral than in the low incidence area. Our preliminary study on ethanol suggests that its effects will be found to lack the complications present with the tannins and would thus be more easily extrapolated to in vivo situations.", "contents": "Effects of gallic acid and of ethanol on formation of nitrosodiethylamine. In vitro experiments demonstrate that the polyphenol, gallic acid, can both catalyse and inhibit NDEA formation. The products of reaction depend considerably on pH conditions and relative concentrations of the reactants. Therefore, interpretation of in vitro experiments in terms of possible in vivo effects in a given population must take into consideration detailed information on eating and drinking habits which might affect pH conditions and relative concentrations of the reactants in the digestive tract. In this respect, it is interesting to note that epidemiological studies conducted by the agency (Day 1) indicate that tea, which contains gallotannins, is consumed more frequently but in a more diluted brew in the area of high oesophageal cancer incidence of the Caspian littoral than in the low incidence area. Our preliminary study on ethanol suggests that its effects will be found to lack the complications present with the tannins and would thus be more easily extrapolated to in vivo situations."}
{"id": "PMID:12090", "title": "Effects of some inhibitors on the nitrosation of drugs in human gastric juice.", "content": "The nitrosation of several drugs under simulated stomach conditions was only weakly inhibited by the beverages studied. With easily and rapidly nitrosatable drugs, such as aminophenazone or piperazine, administered orally, the use of an inhibitor of nitrosation is to be recommended. Of all the substances investigated, ascorbic acid should be regarded as the best inhibitor because of its pronounced activity at the pH values occurring in the stomach and its lack of toxic effects. We would like to propose that the drugs under consideration should be made up to contain a sufficient amount of ascorbic acid.", "contents": "Effects of some inhibitors on the nitrosation of drugs in human gastric juice. The nitrosation of several drugs under simulated stomach conditions was only weakly inhibited by the beverages studied. With easily and rapidly nitrosatable drugs, such as aminophenazone or piperazine, administered orally, the use of an inhibitor of nitrosation is to be recommended. Of all the substances investigated, ascorbic acid should be regarded as the best inhibitor because of its pronounced activity at the pH values occurring in the stomach and its lack of toxic effects. We would like to propose that the drugs under consideration should be made up to contain a sufficient amount of ascorbic acid."}
{"id": "PMID:12092", "title": "Chemical studies on tobacco smoke. XLII. Nitrosonornicotine: presence in tobacco, formation and carcinogenicity.", "content": "NNN is the first organic carcinogen isolated from unburned tobacco. It has been found in smoking tobaccos, chewing tobaccos and in snuff in concentrations between 0.3 and 90.0 mug. This appears to be an unusually high concentration for a nitrosamine in an environmental agent. We have presented data which suggest that NNN, and possibly other unknown nitrosamines, are formed during the curing of tobacco and that the nitrate content of tobacco is an important factor in nitrosamine formation. Studies with N'-methylanabasine applied to tobacco plants are currently under way to test the idea that nicotine rather than nornicotine is the major precursor of NNN in processed tobacco. In mice, NNN induces adenomas of the lung. Bioassays with rats have shown that NNN is carcinogenic to the oesophagus and the nasal cavity. These chemical and biological data are consistent with the observation that tobacco chewers face an increased risk of cancer of the oesophagus. This observation does not, of course, rule out the possibility that other tobacco carcinogens are responsible for the increased cancer risk of tobacco chewers.", "contents": "Chemical studies on tobacco smoke. XLII. Nitrosonornicotine: presence in tobacco, formation and carcinogenicity. NNN is the first organic carcinogen isolated from unburned tobacco. It has been found in smoking tobaccos, chewing tobaccos and in snuff in concentrations between 0.3 and 90.0 mug. This appears to be an unusually high concentration for a nitrosamine in an environmental agent. We have presented data which suggest that NNN, and possibly other unknown nitrosamines, are formed during the curing of tobacco and that the nitrate content of tobacco is an important factor in nitrosamine formation. Studies with N'-methylanabasine applied to tobacco plants are currently under way to test the idea that nicotine rather than nornicotine is the major precursor of NNN in processed tobacco. In mice, NNN induces adenomas of the lung. Bioassays with rats have shown that NNN is carcinogenic to the oesophagus and the nasal cavity. These chemical and biological data are consistent with the observation that tobacco chewers face an increased risk of cancer of the oesophagus. This observation does not, of course, rule out the possibility that other tobacco carcinogens are responsible for the increased cancer risk of tobacco chewers."}
{"id": "PMID:12111", "title": "Microbicidal mechanisms of human granulocytes: synergistic effects of granulocyte elastase and myeloperoxidase or chymotrypsin-like cationic protein.", "content": "The antibacterial activity of a myeloperoxidase (MPO)-glucose oxidase system was found to be greatly increased by granulocyte elastase, present in azurophil granules of human neutrophils. The MPO-H2O3-mediated killing of both Escherichia coli and Staphylococcus aureus was potentiated by granuocyte elastase at an acid pH, whereas at pH 7.4 only killing of E. coli was potentiated. The potentiating effect of elastase was not dependent on the enzymatic properties of the protein since it was not abolished by heating, which destroys the enzymatic activity. A peptide chloromethyl ketone elastase inhibitor abolished both elastolytic activity and the pctentiating effects on MPO-H2-O2-mediated bacterial killing. The antibacterial activity of chymotrypsin-like cationic protein of human neutrophils was also potentiated by elastase. Other degradative enzymes isolated from human granulocytes, e.g., collagenase and lysozyme, did not potentiate MPO-H2O2-mediated or cationic protein-dependent bacterial killing. The present study indicates that a neutrophil constitutent, elastase, which is not microbicidal by itself, can initiate sublethal changes that render some microorganisms more susceptible to the action of microbicidal agents like MPO and chymotrypsin-like cationic protein.", "contents": "Microbicidal mechanisms of human granulocytes: synergistic effects of granulocyte elastase and myeloperoxidase or chymotrypsin-like cationic protein. The antibacterial activity of a myeloperoxidase (MPO)-glucose oxidase system was found to be greatly increased by granulocyte elastase, present in azurophil granules of human neutrophils. The MPO-H2O3-mediated killing of both Escherichia coli and Staphylococcus aureus was potentiated by granuocyte elastase at an acid pH, whereas at pH 7.4 only killing of E. coli was potentiated. The potentiating effect of elastase was not dependent on the enzymatic properties of the protein since it was not abolished by heating, which destroys the enzymatic activity. A peptide chloromethyl ketone elastase inhibitor abolished both elastolytic activity and the pctentiating effects on MPO-H2-O2-mediated bacterial killing. The antibacterial activity of chymotrypsin-like cationic protein of human neutrophils was also potentiated by elastase. Other degradative enzymes isolated from human granulocytes, e.g., collagenase and lysozyme, did not potentiate MPO-H2O2-mediated or cationic protein-dependent bacterial killing. The present study indicates that a neutrophil constitutent, elastase, which is not microbicidal by itself, can initiate sublethal changes that render some microorganisms more susceptible to the action of microbicidal agents like MPO and chymotrypsin-like cationic protein."}
{"id": "PMID:12113", "title": "Effect of bromazepam on gastric acid secretion related to hypnotically induced anxiety.", "content": "The effects of bromazepam (0.1 mg/kg b.w. i.v.) and of placebo on gastric acid secretion related to hypnotically induced anxiety were evaluated in a double blind study, 22 experiments were carried out on 4 healthy volunteers. Drugs were injected after one basal hour. Hypnosis was induced immediately thereafter, and a sequence of anxiety-charged situations out of the subjects past was recalled. After one hour, posthypnotic amnesia was suggested, the subjects awakened and observation continued for another hour. Acid output was measured by means of intragastric titration and a telemetering capsule. During hypnosis and recalling of anxiety in both series, acid output decreased. In the posthypnotic hour there was a significant increase of secretion in the placebo-series, while there was virtually no change in the the bromazepam-series. The pattern of acid output in the placebo-series seems to result from an activation of the sympathetic system under anxiety and a rebound vagal activation in the posthypnotic hour. By contrast, under the sedating effect of bromazepam, no anxiety could be evoked and no rebound vagal activation and thereby no increase of acid secretion resulted.", "contents": "Effect of bromazepam on gastric acid secretion related to hypnotically induced anxiety. The effects of bromazepam (0.1 mg/kg b.w. i.v.) and of placebo on gastric acid secretion related to hypnotically induced anxiety were evaluated in a double blind study, 22 experiments were carried out on 4 healthy volunteers. Drugs were injected after one basal hour. Hypnosis was induced immediately thereafter, and a sequence of anxiety-charged situations out of the subjects past was recalled. After one hour, posthypnotic amnesia was suggested, the subjects awakened and observation continued for another hour. Acid output was measured by means of intragastric titration and a telemetering capsule. During hypnosis and recalling of anxiety in both series, acid output decreased. In the posthypnotic hour there was a significant increase of secretion in the placebo-series, while there was virtually no change in the the bromazepam-series. The pattern of acid output in the placebo-series seems to result from an activation of the sympathetic system under anxiety and a rebound vagal activation in the posthypnotic hour. By contrast, under the sedating effect of bromazepam, no anxiety could be evoked and no rebound vagal activation and thereby no increase of acid secretion resulted."}
{"id": "PMID:12114", "title": "[Effect of fominoben on ventilation, oxygen uptake and blood gases in patients with obstructive ventilation disorders].", "content": "The substituted benzylamin-derivative fominoben (PB 89 Noleptan) was intravenously administered to 12 patients with chronic obstructive lung disease in order to determine, whether an analeptic action on respiration, which had been found by others in animal studies and in healthy subjects, can also be demonstrated in patients with COLD. Time ventilation showed no statistically significant change. Respiratory rate was increased for a short time, alveolar ventilation showed a slight but significant increase 35 minutes after i.v. injection of fominoben, however no significant change in the first 10 minutes after injection.--Arterial pO2 was slightly but not significantly increased in the first 10 minutes after fominoben, while the same patients showed a significant decrease of pO2 after injection of placebo. As alveolar ventilation at this time had not significantly changed, the increase in pO2 can only be explained by an improvement of regional ventilation-perfusion ratio by fominoben. -In conclusion it can be stated, that a marked stimulative action on respiration by fominoben could not be demonstrated. There was, however, no depression of respiration as it is associated with most other caugh medications. As the drug has been shown to be an excellent caugh sedative, lack of respiratory depression can be considered as a considerable advantage.", "contents": "[Effect of fominoben on ventilation, oxygen uptake and blood gases in patients with obstructive ventilation disorders]. The substituted benzylamin-derivative fominoben (PB 89 Noleptan) was intravenously administered to 12 patients with chronic obstructive lung disease in order to determine, whether an analeptic action on respiration, which had been found by others in animal studies and in healthy subjects, can also be demonstrated in patients with COLD. Time ventilation showed no statistically significant change. Respiratory rate was increased for a short time, alveolar ventilation showed a slight but significant increase 35 minutes after i.v. injection of fominoben, however no significant change in the first 10 minutes after injection.--Arterial pO2 was slightly but not significantly increased in the first 10 minutes after fominoben, while the same patients showed a significant decrease of pO2 after injection of placebo. As alveolar ventilation at this time had not significantly changed, the increase in pO2 can only be explained by an improvement of regional ventilation-perfusion ratio by fominoben. -In conclusion it can be stated, that a marked stimulative action on respiration by fominoben could not be demonstrated. There was, however, no depression of respiration as it is associated with most other caugh medications. As the drug has been shown to be an excellent caugh sedative, lack of respiratory depression can be considered as a considerable advantage."}
{"id": "PMID:12115", "title": "Antihypertensive effect of labetalol, a new alpha- and beta-adrenergic blocking agent.", "content": "Labetalol (AH5158) a new alpha- and beta-adrenergic blocking agent was given to 12 hypertensive patients for an average of 7 months. Statistically significant and clinically relevant reductions of blood pressure both in the recumbent and standing positions were observed. Side effects were few and the absence of postural hypotension was noted.", "contents": "Antihypertensive effect of labetalol, a new alpha- and beta-adrenergic blocking agent. Labetalol (AH5158) a new alpha- and beta-adrenergic blocking agent was given to 12 hypertensive patients for an average of 7 months. Statistically significant and clinically relevant reductions of blood pressure both in the recumbent and standing positions were observed. Side effects were few and the absence of postural hypotension was noted."}
{"id": "PMID:12116", "title": "Preliminary experience with vascularised Fallopian tube transplants in the human female.", "content": "The preoperative screening and postoperative case records of two patients that underwent vascularised Fallopian tube transplants are described. In both cases the operation was followed by immunological rejection. This was chronic and clinically quiescent in the first patient, but an accelerated rejection associated with a pyrexial illness and a rise in serum fibrinogen, blood platelet and serum lactic dehydrogenase levels was observed in the second case. Technical feasibility was demonstrated but further progress in the field of Fallopian tube transplants will be dependent on the development of safer techniques of immunosuppression considered necessary for graft survival.", "contents": "Preliminary experience with vascularised Fallopian tube transplants in the human female. The preoperative screening and postoperative case records of two patients that underwent vascularised Fallopian tube transplants are described. In both cases the operation was followed by immunological rejection. This was chronic and clinically quiescent in the first patient, but an accelerated rejection associated with a pyrexial illness and a rise in serum fibrinogen, blood platelet and serum lactic dehydrogenase levels was observed in the second case. Technical feasibility was demonstrated but further progress in the field of Fallopian tube transplants will be dependent on the development of safer techniques of immunosuppression considered necessary for graft survival."}
{"id": "PMID:12117", "title": "Completed pregnancy following vascularized heterotopic autotransplantation of the Fallopian tube in the ewe.", "content": "Transplantation of the Fallopian tube is a technically feasible operation. Previous authors have reported pregnancies following turbo-ovarian transplants, but there appears to be no record of gestation following transplantation of the isolated oviduct. This communication illustrates the method that we have used to perform Fallopian tube transplants in the ewe and documents our first full-term pregnancy following this operation. It provides further evidence of the technical feasibility of Fallopian tube transplants.", "contents": "Completed pregnancy following vascularized heterotopic autotransplantation of the Fallopian tube in the ewe. Transplantation of the Fallopian tube is a technically feasible operation. Previous authors have reported pregnancies following turbo-ovarian transplants, but there appears to be no record of gestation following transplantation of the isolated oviduct. This communication illustrates the method that we have used to perform Fallopian tube transplants in the ewe and documents our first full-term pregnancy following this operation. It provides further evidence of the technical feasibility of Fallopian tube transplants."}
{"id": "PMID:12118", "title": "Hormone-receptor interactions--basic mechanisms.", "content": "An understanding of the basic mechanisms of hormone action is becoming an important part of a clinician's training. With the advent of radioreceptor assays and their comparison with radioimmunoassays, we are becoming increasingly aware that the normal physiological function of a hormone is not necessarily dependent on \"normal\" levels of hormone being present in the plasma. Even if plasma levels are normal, if a particular target cell lacks the receptor for the particular hormone the target tissue will not respond to the hormone. It has been shown, for example, by many workers that steroid hormones act on their cells via a receptor located in the cytoplasm of the target cells (1-4). Since the presence or absence of such receptors are becoming increasingly important in terms of unexplained infertility, endometrial carcinoma and breast cancer, it is necessary that the practicing clinician be familiar with the concept of receptors and have some understanding of their mode of action. In this brief presentation, I will explain certain terminology and summarize the state of the art so that you can critically read the literature concerning new developments in the area of hormone action which is to become increasingly important in the next few years. I will discuss some of the aspects of the mechanism of peptide hormones such as LH and FSH but will devote most of my attention discussing the details of steroid hormone action since our knowledge in this area is much more complete. I will also explain the terms frequently discussed in the literature concerned with hormone-receptor interactions.", "contents": "Hormone-receptor interactions--basic mechanisms. An understanding of the basic mechanisms of hormone action is becoming an important part of a clinician's training. With the advent of radioreceptor assays and their comparison with radioimmunoassays, we are becoming increasingly aware that the normal physiological function of a hormone is not necessarily dependent on \"normal\" levels of hormone being present in the plasma. Even if plasma levels are normal, if a particular target cell lacks the receptor for the particular hormone the target tissue will not respond to the hormone. It has been shown, for example, by many workers that steroid hormones act on their cells via a receptor located in the cytoplasm of the target cells (1-4). Since the presence or absence of such receptors are becoming increasingly important in terms of unexplained infertility, endometrial carcinoma and breast cancer, it is necessary that the practicing clinician be familiar with the concept of receptors and have some understanding of their mode of action. In this brief presentation, I will explain certain terminology and summarize the state of the art so that you can critically read the literature concerning new developments in the area of hormone action which is to become increasingly important in the next few years. I will discuss some of the aspects of the mechanism of peptide hormones such as LH and FSH but will devote most of my attention discussing the details of steroid hormone action since our knowledge in this area is much more complete. I will also explain the terms frequently discussed in the literature concerned with hormone-receptor interactions."}
{"id": "PMID:12119", "title": "Effect of caffeine on the motility, viability, oxygen consumption and glycolytic rate of ejaculated human normokinetic and hypokinetic spermatozoa.", "content": "In this report the effect of caffeine, IBMX and Cholera toxin on ejaculated human spermatozoa was tested. It was found that caffeine was the most effective drug, and that Cholera toxin was ineffective. Caffeine stimulated motility, preserved viability and increased the glucose, fructose utilization and lactate production of sperm in whole semen and washed sperm. Oxygen consumption however was decreased. These results of the normokinetic ejaculates were defined as a basis for comparison with the response of hypokinetic sperm. A group of 11 hypokinetic ejaculated spermatozoa were treated by caffeine and only five responded to caffeine stimulation by a response, similar to that of normokinetic sperm. They were defined as \"responsive.\" The other group of six patients who did not respond were defined as a \"non-responsive\" class. The possibility that the in vitro treated sperm of the responsive class ejaculate is suitable for artificial insemination to their wives, is discussed.", "contents": "Effect of caffeine on the motility, viability, oxygen consumption and glycolytic rate of ejaculated human normokinetic and hypokinetic spermatozoa. In this report the effect of caffeine, IBMX and Cholera toxin on ejaculated human spermatozoa was tested. It was found that caffeine was the most effective drug, and that Cholera toxin was ineffective. Caffeine stimulated motility, preserved viability and increased the glucose, fructose utilization and lactate production of sperm in whole semen and washed sperm. Oxygen consumption however was decreased. These results of the normokinetic ejaculates were defined as a basis for comparison with the response of hypokinetic sperm. A group of 11 hypokinetic ejaculated spermatozoa were treated by caffeine and only five responded to caffeine stimulation by a response, similar to that of normokinetic sperm. They were defined as \"responsive.\" The other group of six patients who did not respond were defined as a \"non-responsive\" class. The possibility that the in vitro treated sperm of the responsive class ejaculate is suitable for artificial insemination to their wives, is discussed."}
{"id": "PMID:12120", "title": "Blastoid transformation of lymphocytes in response to spermatozoa.", "content": "Microlymphocyte transformation tests were done on 33 female rabbits immunized with different components of rabbit ejaculate. In rabbits injected with total ejaculate or washed spermatozoa a specific stimulation of lymphocytes could be demonstrated by exposure to washed spermatozoa. It is shown that it is necessary to notice the length of time for cultivation, the antigen concentration and especially the time-interval after the last immunization.", "contents": "Blastoid transformation of lymphocytes in response to spermatozoa. Microlymphocyte transformation tests were done on 33 female rabbits immunized with different components of rabbit ejaculate. In rabbits injected with total ejaculate or washed spermatozoa a specific stimulation of lymphocytes could be demonstrated by exposure to washed spermatozoa. It is shown that it is necessary to notice the length of time for cultivation, the antigen concentration and especially the time-interval after the last immunization."}
{"id": "PMID:12121", "title": "GPC diesterase activity in human endometrial secretion. (Its variations under the action of estrogens, clomiphene citrate, D-norgestrel (post-coital and low dose) and intrauterine device (IUD).)", "content": "Diesterase activity was studied in human uterine secretions of normal women and in those under treatment for sterility or contraception. Endometrial secretions were obtained from 78 patients and the material divided into four groups: normal women, under different estrogens; with D-Norgestrel treatment (daily and post-coital) and patients with IUD Lippes D. The mean concentration of free choline delivered by the GPC diesterase in the normal group was 777 +/- 128 mug/ml (SD 286). Under hormonal treatment an increase of diesterase activity was observed. D-Norgestrel post-coital produced a fall of the enzymatic activity between 180 to 420 minutes. The uninterrupted use of D-Norgestrel (30 gammas daily) produced a loss of diesterase activity in 80% of cases studied. The use of IUD (Lippes D) did not modify the enzymatic activity in this group.", "contents": "GPC diesterase activity in human endometrial secretion. (Its variations under the action of estrogens, clomiphene citrate, D-norgestrel (post-coital and low dose) and intrauterine device (IUD).). Diesterase activity was studied in human uterine secretions of normal women and in those under treatment for sterility or contraception. Endometrial secretions were obtained from 78 patients and the material divided into four groups: normal women, under different estrogens; with D-Norgestrel treatment (daily and post-coital) and patients with IUD Lippes D. The mean concentration of free choline delivered by the GPC diesterase in the normal group was 777 +/- 128 mug/ml (SD 286). Under hormonal treatment an increase of diesterase activity was observed. D-Norgestrel post-coital produced a fall of the enzymatic activity between 180 to 420 minutes. The uninterrupted use of D-Norgestrel (30 gammas daily) produced a loss of diesterase activity in 80% of cases studied. The use of IUD (Lippes D) did not modify the enzymatic activity in this group."}
{"id": "PMID:12122", "title": "Frequency of Y-chromatin bearing spermatozoa in intracervical and intrauterine postcoital tests.", "content": "By means of the intracervical Sims-Huhner-test and supplementary to this, the intrauterine postcoital test, the percentages of Y-chromatin-positive spermatozoa was determined after penetration into the cervix and the cavum uteri. A significant rise of the Y-positive sperms after penetration could be observed. There was no influence of certain parameters of the spermiogram upon the relationship of X- to Y-sperms after the PCT. Statistical calculations show the dependences of the positive and negative postcoital tests upon the individual parameters of the cervical factors and the spermiogram.", "contents": "Frequency of Y-chromatin bearing spermatozoa in intracervical and intrauterine postcoital tests. By means of the intracervical Sims-Huhner-test and supplementary to this, the intrauterine postcoital test, the percentages of Y-chromatin-positive spermatozoa was determined after penetration into the cervix and the cavum uteri. A significant rise of the Y-positive sperms after penetration could be observed. There was no influence of certain parameters of the spermiogram upon the relationship of X- to Y-sperms after the PCT. Statistical calculations show the dependences of the positive and negative postcoital tests upon the individual parameters of the cervical factors and the spermiogram."}
{"id": "PMID:12123", "title": "Tubal pregnancy in Nigerian Igbos.", "content": "Fifty cases of excised tubal pregnancy which occurred in the Igbos of Nigeria are reviewed. Twenty percent of the tubes were unruptured at the time of excision, indicating a high level of awareness of the condition among local doctors. There were several pointers to the conclusion that, in this ethnic group, tubal pregnancy tends to be seen at an advanced stage. It also tends to occur in the younger women, to manifest during the first known pregnancy, to recur, and to be associated with salpingitis. Interstitial tubal pregnancy is also probably relatively common.", "contents": "Tubal pregnancy in Nigerian Igbos. Fifty cases of excised tubal pregnancy which occurred in the Igbos of Nigeria are reviewed. Twenty percent of the tubes were unruptured at the time of excision, indicating a high level of awareness of the condition among local doctors. There were several pointers to the conclusion that, in this ethnic group, tubal pregnancy tends to be seen at an advanced stage. It also tends to occur in the younger women, to manifest during the first known pregnancy, to recur, and to be associated with salpingitis. Interstitial tubal pregnancy is also probably relatively common."}
{"id": "PMID:12124", "title": "The necessity for bilateral biopsy in oligo- and azospermia.", "content": "The 384 testicles from 192 infertile men were examined by bilateral biopsy. The main reason of this investigation was to see whether differences in the varying degrees of damage to the seminal epithelium existed in both testicles. Depending on the damage, the material was divided into five groups. The conclusion is, that the greater the degree of damage, the greater are the differences in the findings in both testicles. The left testis was more often and more strongly damaged than the right.", "contents": "The necessity for bilateral biopsy in oligo- and azospermia. The 384 testicles from 192 infertile men were examined by bilateral biopsy. The main reason of this investigation was to see whether differences in the varying degrees of damage to the seminal epithelium existed in both testicles. Depending on the damage, the material was divided into five groups. The conclusion is, that the greater the degree of damage, the greater are the differences in the findings in both testicles. The left testis was more often and more strongly damaged than the right."}
{"id": "PMID:12130", "title": "Alterations in the coronary circulation of man following ascent to 3,100 m altitude.", "content": "Alterations in coronary blood flow associated with adaptation to high altitude were examined. Three normal men native to low altitude were studied, first at sea level, and again after 10 days' sojourn at 3,100 m altitude. During rest at high altitude, a 32% decrease in coronary blood flow was largely offset by a 28% increase in coronary arterial O2 extraction to maintain myocardial O2 delivery. The increase in O2 extraction resulted mainly from a decrease in coronary sinus blood O2 content and saturation. However, coronary sinus O2 tension remained constant, implying a decrease in the affinity of hemoglobin for O2. These observations are consistent with the hypothesis that coronary blood flow is regulated to maintain constant myocardial tissue O2 tension (as reflected here by coronary sinus blood O2 tension). The absence of a decrease in coronary sinus O2 tension or a decrease in myocardial lactate extraction imply that myocardial hypoxia did not develop. Therefore, myocardial hypoxia is not the basis for the decrease in cardiac stroke volume at high altitude reported previously and also observed in the present study.", "contents": "Alterations in the coronary circulation of man following ascent to 3,100 m altitude. Alterations in coronary blood flow associated with adaptation to high altitude were examined. Three normal men native to low altitude were studied, first at sea level, and again after 10 days' sojourn at 3,100 m altitude. During rest at high altitude, a 32% decrease in coronary blood flow was largely offset by a 28% increase in coronary arterial O2 extraction to maintain myocardial O2 delivery. The increase in O2 extraction resulted mainly from a decrease in coronary sinus blood O2 content and saturation. However, coronary sinus O2 tension remained constant, implying a decrease in the affinity of hemoglobin for O2. These observations are consistent with the hypothesis that coronary blood flow is regulated to maintain constant myocardial tissue O2 tension (as reflected here by coronary sinus blood O2 tension). The absence of a decrease in coronary sinus O2 tension or a decrease in myocardial lactate extraction imply that myocardial hypoxia did not develop. Therefore, myocardial hypoxia is not the basis for the decrease in cardiac stroke volume at high altitude reported previously and also observed in the present study."}
{"id": "PMID:12127", "title": "Reduced red cell membrane potential and acidification of the plasma in response to contrast materials. Time course of the alteration in plasma pH.", "content": "Radiographic contrast materials added to blood reduce the red cell membrane potential by balancing the internal impenetrable anions, hemoglobin and organic phosphates. In so doing, a redistribution of protons occurs such that plasma is acidified. The time course of acidification of plasma is measured in seconds, with a nadir of pH occurring 12 to 15 seconds after addition of Hypaque (1.5 to 3.0 ml/10 ml blood) and a half-time of acidification requiring about 6 seconds. The acidification process is slowed in part by an initial alkalosis due to Hypaque. The acidification of blood is more rapid after addition of Renografin (1.5 to 3.0 ml/10 ml blood) than after addition of Hypaque since the former solution is slightly acidic. The time course of plasma acidification indicates that a maximal reduction in blood pH may not occur in the capillaries of a regional circulation following injection of contrast materials into its afferent vessel, since the transit time of the contrast material may be less than the time required for maximal acidification of plasma.", "contents": "Reduced red cell membrane potential and acidification of the plasma in response to contrast materials. Time course of the alteration in plasma pH. Radiographic contrast materials added to blood reduce the red cell membrane potential by balancing the internal impenetrable anions, hemoglobin and organic phosphates. In so doing, a redistribution of protons occurs such that plasma is acidified. The time course of acidification of plasma is measured in seconds, with a nadir of pH occurring 12 to 15 seconds after addition of Hypaque (1.5 to 3.0 ml/10 ml blood) and a half-time of acidification requiring about 6 seconds. The acidification process is slowed in part by an initial alkalosis due to Hypaque. The acidification of blood is more rapid after addition of Renografin (1.5 to 3.0 ml/10 ml blood) than after addition of Hypaque since the former solution is slightly acidic. The time course of plasma acidification indicates that a maximal reduction in blood pH may not occur in the capillaries of a regional circulation following injection of contrast materials into its afferent vessel, since the transit time of the contrast material may be less than the time required for maximal acidification of plasma."}
{"id": "PMID:12131", "title": "Ventilation in conscious dogs during acute and chronic hypercapnia.", "content": "Minute ventilation was measured in conscious dogs, at rest and during exercise (1 mph), over 60 min immediately following the acute inhalation of 5% carbon dioxide in air and at 2, 4, 7, and 14 days while breathing the same gas mixture in a chamber. The dogs were also studied in the immediate period of air recovery from chronic hypercapnia and 1 day later. Control studies were carried out with the dogs breathing air in the chamber under comparable conditions. A triphasic ventilation change was ovserved in dogs at rest over the 14 days of hypercapnia. After an initial marked increase in ventilation during acute hypercapnia, ventilation returned to control levels by 2 days and then appeared to be elevated above control studies from 4 to 14 days at a time when blood acid-base balance became compensated. When the same dogs were studied during exercise, ventilation was also not different from air control at 2 days of hypercapnia; however during exercise, unlike the resting studies, there was only a tendency for a secondary increase in ventilation at 7 and 14 days of hypercapnia. During the immediate recovery from chronic hypercapnia when the dogs breathed air there was no evidence of hypoventilation either at rest or exercise despite arterial alkalosis. At 24 h of recovery it appeared that dogs while at rest had a slightly reduced ventilatory response to 5% carbon dioxide relative to control studies. The findings provide suggestive evidence that other factors, in addition to acid-base balance, might contribute to the regulation of ventilation during chronic hypercapnia and the recovery from chronic hypercapnia.", "contents": "Ventilation in conscious dogs during acute and chronic hypercapnia. Minute ventilation was measured in conscious dogs, at rest and during exercise (1 mph), over 60 min immediately following the acute inhalation of 5% carbon dioxide in air and at 2, 4, 7, and 14 days while breathing the same gas mixture in a chamber. The dogs were also studied in the immediate period of air recovery from chronic hypercapnia and 1 day later. Control studies were carried out with the dogs breathing air in the chamber under comparable conditions. A triphasic ventilation change was ovserved in dogs at rest over the 14 days of hypercapnia. After an initial marked increase in ventilation during acute hypercapnia, ventilation returned to control levels by 2 days and then appeared to be elevated above control studies from 4 to 14 days at a time when blood acid-base balance became compensated. When the same dogs were studied during exercise, ventilation was also not different from air control at 2 days of hypercapnia; however during exercise, unlike the resting studies, there was only a tendency for a secondary increase in ventilation at 7 and 14 days of hypercapnia. During the immediate recovery from chronic hypercapnia when the dogs breathed air there was no evidence of hypoventilation either at rest or exercise despite arterial alkalosis. At 24 h of recovery it appeared that dogs while at rest had a slightly reduced ventilatory response to 5% carbon dioxide relative to control studies. The findings provide suggestive evidence that other factors, in addition to acid-base balance, might contribute to the regulation of ventilation during chronic hypercapnia and the recovery from chronic hypercapnia."}
{"id": "PMID:12128", "title": "Electrophoretic properties of temperature-sensitive mutant particles of simian virus 40.", "content": "Forty-five temperature-sensitive strains of simian virus 40 (SV40) particles belonging to four complementation groups were analyzed by agarose gel electrophoresis. Five strains (B204, B218, B233, and BC226), which are members of the B and BC complementation groups, yielded virions with aberrant mobilities. Genetic mapping by LAI and NATHANS suggested that B and BC mutantions are in a single gene. The mutant virions possessing altered mobilities have greater positive charges than wild-type particles. The findings presented here indicate that the product of gene B and BC is a significant component of the SV40 capsid.", "contents": "Electrophoretic properties of temperature-sensitive mutant particles of simian virus 40. Forty-five temperature-sensitive strains of simian virus 40 (SV40) particles belonging to four complementation groups were analyzed by agarose gel electrophoresis. Five strains (B204, B218, B233, and BC226), which are members of the B and BC complementation groups, yielded virions with aberrant mobilities. Genetic mapping by LAI and NATHANS suggested that B and BC mutantions are in a single gene. The mutant virions possessing altered mobilities have greater positive charges than wild-type particles. The findings presented here indicate that the product of gene B and BC is a significant component of the SV40 capsid."}
{"id": "PMID:12132", "title": "Influence of carbon monoxide on hemoglobin-oxygen binding.", "content": "The oxygen dissociation curve and Bohr effect were measured in normal whole blood as a function of carboxyhemoglobin concentration [HbCO]. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HCl at constant PCO2 (fixed acid Bohr effect). As [HbCO] varied through the range of 2, 25, 50, and 75%, P50 was 26.3, 18.0, 11.6, and 6.5 mmHg, respectively. CO2 Bohr effect was highest at low oxygen saturations. This effect did not change as [HbCO] was increased. However, as [HbCO] was increased from 2 to 75%, the fixed acid Bohr factor increased in magnitude from -0.20 to -0.80 at very low oxygen saturations. The effect of molecular CO2 binding (carbamino) on oxygen affinity was eliminated at high [HbCO]. These results are consistent with the initial binding of O2 or CO to the alpha-chain of hemoglobin. The results also suggest that heme-heme interaction is different for oxygen than for carbon monoxide.", "contents": "Influence of carbon monoxide on hemoglobin-oxygen binding. The oxygen dissociation curve and Bohr effect were measured in normal whole blood as a function of carboxyhemoglobin concentration [HbCO]. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HCl at constant PCO2 (fixed acid Bohr effect). As [HbCO] varied through the range of 2, 25, 50, and 75%, P50 was 26.3, 18.0, 11.6, and 6.5 mmHg, respectively. CO2 Bohr effect was highest at low oxygen saturations. This effect did not change as [HbCO] was increased. However, as [HbCO] was increased from 2 to 75%, the fixed acid Bohr factor increased in magnitude from -0.20 to -0.80 at very low oxygen saturations. The effect of molecular CO2 binding (carbamino) on oxygen affinity was eliminated at high [HbCO]. These results are consistent with the initial binding of O2 or CO to the alpha-chain of hemoglobin. The results also suggest that heme-heme interaction is different for oxygen than for carbon monoxide."}
{"id": "PMID:12133", "title": "Partial purification and some properties of delta1-pyrroline-5-carboxylate reductase from Escherichia coli.", "content": "delta1-Pyrroline-5-carboxylate (PCA) reductase [L-proline:NAD(P)+5-oxidoreductase, EC 1.5.1.2] has been purified over 200-fold from Escherichia coli K-12. It has a molecular weight of approximately 320,000. PCA reductase mediates the pyridine nucleotide-linked reduction of PCA to proline but not the reverse reaction (even at high substrate concentrations). The partially purified preparation is free of competing pyridine nucleotide oxidase, PCA dehydrogenase, and proline oxidase activities. The Michaelis constant (Km) values for the substrate, PCA, with reduced nicotinamide adenine dinucleotide phosphate (NADPH) or NADH as cofactor are 0.15 and 0.14 mM, respectively. The Km values determined for NADPH and NADH are 0.03 and 0.23 mM, respectively. Although either NADPH or NADH can function as cofactor, the activity observed with NADPH is severalfold greater. PCA reductase is not repressed by growth in the presence of proline, but it is inhibited by the reaction end products, proline and NADP.", "contents": "Partial purification and some properties of delta1-pyrroline-5-carboxylate reductase from Escherichia coli. delta1-Pyrroline-5-carboxylate (PCA) reductase [L-proline:NAD(P)+5-oxidoreductase, EC 1.5.1.2] has been purified over 200-fold from Escherichia coli K-12. It has a molecular weight of approximately 320,000. PCA reductase mediates the pyridine nucleotide-linked reduction of PCA to proline but not the reverse reaction (even at high substrate concentrations). The partially purified preparation is free of competing pyridine nucleotide oxidase, PCA dehydrogenase, and proline oxidase activities. The Michaelis constant (Km) values for the substrate, PCA, with reduced nicotinamide adenine dinucleotide phosphate (NADPH) or NADH as cofactor are 0.15 and 0.14 mM, respectively. The Km values determined for NADPH and NADH are 0.03 and 0.23 mM, respectively. Although either NADPH or NADH can function as cofactor, the activity observed with NADPH is severalfold greater. PCA reductase is not repressed by growth in the presence of proline, but it is inhibited by the reaction end products, proline and NADP."}
{"id": "PMID:12134", "title": "Chemotaxis toward amino acids by Bacillus subtilis.", "content": "Conditions for assaying chemotaxis in Bacillus subtilis are described. The chemotaxis medium we used afforded excellent motility for hours. In it, chemotaxis measured by capillary assays was insensitive to pH between 5.5 and 9, and to temperature between 28 degrees C and 42 degrees C. Chemotaxis was observed toward all 20 common amino acids, with thresholds varying from 3nM for alanine to 0.1 mM for glutamate, in the capillary assay, and from 0.1 muM for alanine to 0.32 mM for glutamate in the microscope assay.", "contents": "Chemotaxis toward amino acids by Bacillus subtilis. Conditions for assaying chemotaxis in Bacillus subtilis are described. The chemotaxis medium we used afforded excellent motility for hours. In it, chemotaxis measured by capillary assays was insensitive to pH between 5.5 and 9, and to temperature between 28 degrees C and 42 degrees C. Chemotaxis was observed toward all 20 common amino acids, with thresholds varying from 3nM for alanine to 0.1 mM for glutamate, in the capillary assay, and from 0.1 muM for alanine to 0.32 mM for glutamate in the microscope assay."}
{"id": "PMID:12135", "title": "Properties of tyrosine-inhibitable 3-deoxy-d-arabinoheptulosonic acid-7-phosphate synthase from Salmonella.", "content": "Tyrosine-inhibitable 3-deoxy-D-arabinoheptulosonic acid-7-phosphate (DAHP) synthase was purified to homogeneity without significant loss of sensitivity to inhibition by tyrosine from an operator-constitutive strain (tyrOc) of Salmonella. The enzyme had an apparent molecular weight of 76,000 by gel filtration and a subunit molecular weight of 40,000 by sodium dodecyl sulfate-gel electrophoresis and by reaction with dimethyl suberimidate. It had an isoelectric point of 4.68. Inhibition by L-tyrosine showed a Hill coefficient of 1.8 at pH 7.0, suggesting cooperative interaction between tyrosine-binding sites, and was competitive with phosphoenol pyruvate and noncompetitive with erythrose-4-phosphate.", "contents": "Properties of tyrosine-inhibitable 3-deoxy-d-arabinoheptulosonic acid-7-phosphate synthase from Salmonella. Tyrosine-inhibitable 3-deoxy-D-arabinoheptulosonic acid-7-phosphate (DAHP) synthase was purified to homogeneity without significant loss of sensitivity to inhibition by tyrosine from an operator-constitutive strain (tyrOc) of Salmonella. The enzyme had an apparent molecular weight of 76,000 by gel filtration and a subunit molecular weight of 40,000 by sodium dodecyl sulfate-gel electrophoresis and by reaction with dimethyl suberimidate. It had an isoelectric point of 4.68. Inhibition by L-tyrosine showed a Hill coefficient of 1.8 at pH 7.0, suggesting cooperative interaction between tyrosine-binding sites, and was competitive with phosphoenol pyruvate and noncompetitive with erythrose-4-phosphate."}
{"id": "PMID:12136", "title": "Vesicle penicillinase of Bacillus licheniformis: existence of periplasmic-releasing factor(s).", "content": "In earlier studies of the membrane-bound penicillinase of Bacillus licheniformis 749/C, the enzyme present in the vesicles that were released during protoplast formation and the enzyme retained in the plasma membrane of protoplasts appeared to differ (i) in their behavior on gel permeation chromatography in the presence or absence of deoxycholate and (ii) in their tendency to convert to the hydrophilic exoenzyme (Sargent and Lampen, 1970). We have now shown that these vesicle preparations contain a soluble, heat-sensitive enzyme(s) that is released along with the vesicles during protoplast formation. The enzyme will convert the vesicle penicillinase to a form that resembles exopenicillinase, and this conversion can be inhibited by deoxycholate under certain circumstances. Sedimentation of such vesicle preparations at 100,000 X g produces vesicles which contain penicillinase that behaves as the plasma membrane enzyme obtained from protoplasts. Exopenicillinases released by growing cells at pH 6.5 and by washed cells or protoplasts at pH 9.0 have the same NH2-terminal residues (lysine and some glutamic acid); in addition, the various release systems show a parallel sensitivity to inhibition by deoxycholate, quinacrine, chloroquine, and o-phenanthroline. The formation of exopenicillinase (by cleavage of the membrane-bound enzyme) may well be dependent on the action of the releasing enzyme.", "contents": "Vesicle penicillinase of Bacillus licheniformis: existence of periplasmic-releasing factor(s). In earlier studies of the membrane-bound penicillinase of Bacillus licheniformis 749/C, the enzyme present in the vesicles that were released during protoplast formation and the enzyme retained in the plasma membrane of protoplasts appeared to differ (i) in their behavior on gel permeation chromatography in the presence or absence of deoxycholate and (ii) in their tendency to convert to the hydrophilic exoenzyme (Sargent and Lampen, 1970). We have now shown that these vesicle preparations contain a soluble, heat-sensitive enzyme(s) that is released along with the vesicles during protoplast formation. The enzyme will convert the vesicle penicillinase to a form that resembles exopenicillinase, and this conversion can be inhibited by deoxycholate under certain circumstances. Sedimentation of such vesicle preparations at 100,000 X g produces vesicles which contain penicillinase that behaves as the plasma membrane enzyme obtained from protoplasts. Exopenicillinases released by growing cells at pH 6.5 and by washed cells or protoplasts at pH 9.0 have the same NH2-terminal residues (lysine and some glutamic acid); in addition, the various release systems show a parallel sensitivity to inhibition by deoxycholate, quinacrine, chloroquine, and o-phenanthroline. The formation of exopenicillinase (by cleavage of the membrane-bound enzyme) may well be dependent on the action of the releasing enzyme."}
{"id": "PMID:12137", "title": "Penicillinase-releasing protease of Bacillus licheniformis: purification and general properties.", "content": "The membrane penicillinase of Bacillus licheniformis 749/C is a phospholipoprotein which differs from the exoenzyme in that it has an additional sequence of 24 amino acid residues and a phosphatidylserine at the NH2 terminus. In exponential-phase cultures, the conversion of membrane penicillinase to exoenzyme occurs at neutral and alkaline pH. An enzyme that will cleave the membrane penicillinase to yield the exoenzyme is present (in small amounts) in exponential-phase cells and is released during their conversion to protoplasts. The enzyme is found in the filtrate of a stationary-phase culture of the uninduced penicillinase-inducible strain 749 and has been purified to apparent homogeneity from this source. The protease has an approximate molecular weight of 21,500 and requires Ca2+ ions for stabilization. It has a pH optimum of 7.0 to 9.5 for hydrolysis of casein and for the cleavage of membrane penicillinase. Both activities are inhibited by diisopropylfluorophosphate; hence, the enzyme is a serine protease. This enzyme may be entirely responsible for the formation of exopenicillinase by this organism, since the other neutral and alkaline proteases of strain 749 have little, if any, activity in releasing exopenicillinase. The enzyme has been termed penicillinase-releasing protease.", "contents": "Penicillinase-releasing protease of Bacillus licheniformis: purification and general properties. The membrane penicillinase of Bacillus licheniformis 749/C is a phospholipoprotein which differs from the exoenzyme in that it has an additional sequence of 24 amino acid residues and a phosphatidylserine at the NH2 terminus. In exponential-phase cultures, the conversion of membrane penicillinase to exoenzyme occurs at neutral and alkaline pH. An enzyme that will cleave the membrane penicillinase to yield the exoenzyme is present (in small amounts) in exponential-phase cells and is released during their conversion to protoplasts. The enzyme is found in the filtrate of a stationary-phase culture of the uninduced penicillinase-inducible strain 749 and has been purified to apparent homogeneity from this source. The protease has an approximate molecular weight of 21,500 and requires Ca2+ ions for stabilization. It has a pH optimum of 7.0 to 9.5 for hydrolysis of casein and for the cleavage of membrane penicillinase. Both activities are inhibited by diisopropylfluorophosphate; hence, the enzyme is a serine protease. This enzyme may be entirely responsible for the formation of exopenicillinase by this organism, since the other neutral and alkaline proteases of strain 749 have little, if any, activity in releasing exopenicillinase. The enzyme has been termed penicillinase-releasing protease."}
{"id": "PMID:12138", "title": "Carboxylation of phosphoenolpyruvate by extracts of Neisseria gonorrhoeae.", "content": "The enzymatic carboxylation of phosphoenolpyruvate by cell-free extracts of Neisseria gonorrhoeae was examined and determined to be similar to the reaction catalyzed by phosphoenolpyruvate carboxylase (PEPC). This was shown by the irreversibility of the reaction and nucleotide independency. The enzyme was found to have some characteristics different from the other bacterial PEPCs reported. The enzyme showed catalytic activity in the presence of cobalt ions as well as magnesium and manganese ions, was not inhibited by succinate in fresh extracts, and displayed a low Michaelis constant for bicarbonate (0.27 mM), as compared with other PEPCs. The significance of this low Michaelis constant is discussed with respect to the growth of the organism and the importance of this enzyme to protein and nucleic acid synthesis.", "contents": "Carboxylation of phosphoenolpyruvate by extracts of Neisseria gonorrhoeae. The enzymatic carboxylation of phosphoenolpyruvate by cell-free extracts of Neisseria gonorrhoeae was examined and determined to be similar to the reaction catalyzed by phosphoenolpyruvate carboxylase (PEPC). This was shown by the irreversibility of the reaction and nucleotide independency. The enzyme was found to have some characteristics different from the other bacterial PEPCs reported. The enzyme showed catalytic activity in the presence of cobalt ions as well as magnesium and manganese ions, was not inhibited by succinate in fresh extracts, and displayed a low Michaelis constant for bicarbonate (0.27 mM), as compared with other PEPCs. The significance of this low Michaelis constant is discussed with respect to the growth of the organism and the importance of this enzyme to protein and nucleic acid synthesis."}
{"id": "PMID:12139", "title": "Mismatch excision and possible polarity effects result in preferred deoxyribonucleic acid strand of integration in pneumococcal transformation.", "content": "Heteroduplex deoxyribonucleic acid molecules having a drug resistance marker on one strand and its wild-type allele on the other have been used as donors in pneumococcal transformation. Opposite strands are not equally effective in producing transformants, and this strand bias is not the same, either in direction or magnitude, for various different genetic markers. Selective excision of mismatched base pairs is probably responsible for the large differences in strand efficiency seen with discriminating (hex+) strains, for when the recipient is nondiscriminating (hex-), and therefore presumably lacking an excision enzyme system, strand bias is drastically reduced or altered. The evidence also indicates that excision occurs after integration, as it is provoked by specific donor-recipient mismatch and not by the same mismatch when introduced within donor heteroduplex molecules. Excision can extend to include a neighboring linked marker which would otherwise not be excised, thus altering its intrinsic strand bias as well as its efficiency in transformation. There is a small bias in relative strand efficiency for some markers, not caused by mismatch excision, which perhaps is due to polarity in the integration process itself.", "contents": "Mismatch excision and possible polarity effects result in preferred deoxyribonucleic acid strand of integration in pneumococcal transformation. Heteroduplex deoxyribonucleic acid molecules having a drug resistance marker on one strand and its wild-type allele on the other have been used as donors in pneumococcal transformation. Opposite strands are not equally effective in producing transformants, and this strand bias is not the same, either in direction or magnitude, for various different genetic markers. Selective excision of mismatched base pairs is probably responsible for the large differences in strand efficiency seen with discriminating (hex+) strains, for when the recipient is nondiscriminating (hex-), and therefore presumably lacking an excision enzyme system, strand bias is drastically reduced or altered. The evidence also indicates that excision occurs after integration, as it is provoked by specific donor-recipient mismatch and not by the same mismatch when introduced within donor heteroduplex molecules. Excision can extend to include a neighboring linked marker which would otherwise not be excised, thus altering its intrinsic strand bias as well as its efficiency in transformation. There is a small bias in relative strand efficiency for some markers, not caused by mismatch excision, which perhaps is due to polarity in the integration process itself."}
{"id": "PMID:12140", "title": "Ultrastructural, physiological, and cytochemical characterization of cores in group D streptococci.", "content": "Cores are large, rod-shaped structures that have been found almost exclusively in group D streptococci, measure 0.1 to 0.16 mum in diameter, and extend the width or length of cells. This study has shown that cores are produced in the cells at a reproducible point in early stationary growth after extensive mesosomal formation and after the pH has dropped below 6.5. When cells containing cores were introduced into a fresh medium with a pH above 6.5, the structures disappeared within 5 min. The structures were not found in young, logarithmically growing cells but formed in these cells upon autolysis or treatment with penicillin. Cores that were forming or disintegrating appeared to have a lamellar substructure. When chloramphenicol was added to the medium before the culture reached stationary phase, no cores were found in the cells. Cytochemical studies indicated that cores contain protein and are not composed of cell wall material or other polysaccharides that contain 1,2-glycol groups.", "contents": "Ultrastructural, physiological, and cytochemical characterization of cores in group D streptococci. Cores are large, rod-shaped structures that have been found almost exclusively in group D streptococci, measure 0.1 to 0.16 mum in diameter, and extend the width or length of cells. This study has shown that cores are produced in the cells at a reproducible point in early stationary growth after extensive mesosomal formation and after the pH has dropped below 6.5. When cells containing cores were introduced into a fresh medium with a pH above 6.5, the structures disappeared within 5 min. The structures were not found in young, logarithmically growing cells but formed in these cells upon autolysis or treatment with penicillin. Cores that were forming or disintegrating appeared to have a lamellar substructure. When chloramphenicol was added to the medium before the culture reached stationary phase, no cores were found in the cells. Cytochemical studies indicated that cores contain protein and are not composed of cell wall material or other polysaccharides that contain 1,2-glycol groups."}
{"id": "PMID:12141", "title": "Casamino acids enhance growth of Bacteroides melaninogenicus.", "content": "Casamino Acids enhance the growth of Bacteroides melaninogenicus when added to various concentrations of Trypticase. Absence of a peptide, not amino acids, is responsible for the inability of Casamino Acids to support growth.", "contents": "Casamino acids enhance growth of Bacteroides melaninogenicus. Casamino Acids enhance the growth of Bacteroides melaninogenicus when added to various concentrations of Trypticase. Absence of a peptide, not amino acids, is responsible for the inability of Casamino Acids to support growth."}
{"id": "PMID:12142", "title": "The chemical modification of beef liver catalase. V. Ethoxyformylation of histidine and tyrosine residues of catalase with diethylpyrocarbonate.", "content": "In order to elucidate the possible roles of histidine and tyrosine residues of catalase [EC 1.11.1.6] in maintaining the quaternary structure and catalatic activity, diethylpyrocarbonate modification experiments were carried out. A method for the estimation of N-ethoxyformyl (EF)-His at pH 5--7 and of O-ethoxyformyl (EF)-Tyr in alkaline solution by measuring A 242 nm (ximM = 3.2) and A278 nm (ximM = 1.16), respectively, was developed. The formation of EF-His and EF-Tyr was an electrophilic reaction and was dependent on pH, exhibiting pK values of 6.8 and 9.9, respectively. The maximal yield of EF-His at pH 6.0 was 49% of the total histidine content, but no inactivation nor unfolding of the enzyme was observed. The formation of 12 EF-Tyr residues per mole of catalase at pH 8.1 did not cause any inactivation, but the formation of 8 more EF-Tyr residues at pH 8.9 resulted in both inactivation and unfolding. Nearly complete inactivation and partial splitting of catalase were observed when 43-46 EF-Tyr residues per mole were produced at pH 10.0. More EF-His residues were formed by the reaction of diethyl pyrocarbonate with cyanoethylated (CE)-catalase monomer (subunit) than with CE-catalase tetramer. The CE-catalase tetramer and monomer were extensively O-ethoxyformylated, reaching 100% EF-Tyr formation. These results indicate that a half of the histidine residues may lie outside the protein core and that three-quarters of the tyrosine residues are probably in the protein core of the enzyme. The production of 2--3 EF-Tyr residues per mole of the monomer by ethoxyformylation at pH 7.0 was accompanied by a decrease in the magnitude of the Soret peak. A possible interaction of those tyrosine residues with porphyrin of the heme group is discussed.", "contents": "The chemical modification of beef liver catalase. V. Ethoxyformylation of histidine and tyrosine residues of catalase with diethylpyrocarbonate. In order to elucidate the possible roles of histidine and tyrosine residues of catalase [EC 1.11.1.6] in maintaining the quaternary structure and catalatic activity, diethylpyrocarbonate modification experiments were carried out. A method for the estimation of N-ethoxyformyl (EF)-His at pH 5--7 and of O-ethoxyformyl (EF)-Tyr in alkaline solution by measuring A 242 nm (ximM = 3.2) and A278 nm (ximM = 1.16), respectively, was developed. The formation of EF-His and EF-Tyr was an electrophilic reaction and was dependent on pH, exhibiting pK values of 6.8 and 9.9, respectively. The maximal yield of EF-His at pH 6.0 was 49% of the total histidine content, but no inactivation nor unfolding of the enzyme was observed. The formation of 12 EF-Tyr residues per mole of catalase at pH 8.1 did not cause any inactivation, but the formation of 8 more EF-Tyr residues at pH 8.9 resulted in both inactivation and unfolding. Nearly complete inactivation and partial splitting of catalase were observed when 43-46 EF-Tyr residues per mole were produced at pH 10.0. More EF-His residues were formed by the reaction of diethyl pyrocarbonate with cyanoethylated (CE)-catalase monomer (subunit) than with CE-catalase tetramer. The CE-catalase tetramer and monomer were extensively O-ethoxyformylated, reaching 100% EF-Tyr formation. These results indicate that a half of the histidine residues may lie outside the protein core and that three-quarters of the tyrosine residues are probably in the protein core of the enzyme. The production of 2--3 EF-Tyr residues per mole of the monomer by ethoxyformylation at pH 7.0 was accompanied by a decrease in the magnitude of the Soret peak. A possible interaction of those tyrosine residues with porphyrin of the heme group is discussed."}
{"id": "PMID:12143", "title": "Involvement of cyclic GMP in the initial stage of hepatocytes proliferation.", "content": "A transient rise in cyclic guanosine 3' : 5' monophosphate (c-GMP) in the liver was observed in rats in vivo 10--20 min after partial hepatectomy. A similar increase in c-GMP in the liver was also found in rats in vivo 15 min after infusion of TGH solution (a mixture of triiodothyronine, glucagon, and heparin). In both cases, inductions of ornithine decarboxylase [EC 4.1.1.17] and tyrosine aminotransferase [EC 2.6.1.5] were found 4 hr after the beginning of the experiments. Later, 22 hr after the surgical intervention or hormone infusion, thymidine kinase [EC 2.7.1.21] was activated and liver slices were able to incorporate [3H]thymidine into DNA. These biochemical phenomena were observed commonly in regenerating liver as well as in the liver of rats infused with TGH solution. c-GMP, but not c-AMP, could induce ornithine decarboxylase and tyrosine aminotransferase in isolated, perfused liver.", "contents": "Involvement of cyclic GMP in the initial stage of hepatocytes proliferation. A transient rise in cyclic guanosine 3' : 5' monophosphate (c-GMP) in the liver was observed in rats in vivo 10--20 min after partial hepatectomy. A similar increase in c-GMP in the liver was also found in rats in vivo 15 min after infusion of TGH solution (a mixture of triiodothyronine, glucagon, and heparin). In both cases, inductions of ornithine decarboxylase [EC 4.1.1.17] and tyrosine aminotransferase [EC 2.6.1.5] were found 4 hr after the beginning of the experiments. Later, 22 hr after the surgical intervention or hormone infusion, thymidine kinase [EC 2.7.1.21] was activated and liver slices were able to incorporate [3H]thymidine into DNA. These biochemical phenomena were observed commonly in regenerating liver as well as in the liver of rats infused with TGH solution. c-GMP, but not c-AMP, could induce ornithine decarboxylase and tyrosine aminotransferase in isolated, perfused liver."}
{"id": "PMID:12144", "title": "Studies on phospholipase A in Trimeresurus flaoviridis venom. III. Purification and some properties of phospholipase A inhibitor in Habu serum.", "content": "Phospholipase A [EC 3.1.1.4] inhibitor was purified from Habu (Trimeresurus flavivurudls) serum by gel filtration on Sephadex G-200, chromatography on DE-23 cellulose and affinity chromatography on a Sepharose 4B-phospholipase A column. By these procedures, a 31-fold increase in specific activity was attained with a yield of 15%. The purified material was homogeneous as judged by cellulose acetate and polyacrylamide gel electrophoresis. It had an apparent molecular weight of 100,000 as measured by gel filtration on Sephadex G-200. The purified inhibitor was stable for 20 min at 80 degrees and was unstable below pH 6. It migrated before albumin in cellulose acetate electrophoresis and did not form any precipitin line with the crude venom or with purified phospholipase A in immunodiffusin tests. An 8-fold excess of the purified inhibitor by weight was required to inhibit completely both the egg yolk clearing action and the hemolytic action of phospholipase A.", "contents": "Studies on phospholipase A in Trimeresurus flaoviridis venom. III. Purification and some properties of phospholipase A inhibitor in Habu serum. Phospholipase A [EC 3.1.1.4] inhibitor was purified from Habu (Trimeresurus flavivurudls) serum by gel filtration on Sephadex G-200, chromatography on DE-23 cellulose and affinity chromatography on a Sepharose 4B-phospholipase A column. By these procedures, a 31-fold increase in specific activity was attained with a yield of 15%. The purified material was homogeneous as judged by cellulose acetate and polyacrylamide gel electrophoresis. It had an apparent molecular weight of 100,000 as measured by gel filtration on Sephadex G-200. The purified inhibitor was stable for 20 min at 80 degrees and was unstable below pH 6. It migrated before albumin in cellulose acetate electrophoresis and did not form any precipitin line with the crude venom or with purified phospholipase A in immunodiffusin tests. An 8-fold excess of the purified inhibitor by weight was required to inhibit completely both the egg yolk clearing action and the hemolytic action of phospholipase A."}
{"id": "PMID:12145", "title": "Studies on triglyceride lipases from rat adipose tissue.", "content": "A new assay procedure for triglyceride lipase [EC 3.1.1.3] was developed in which radioactive triolein was dissolved in ethanol and directly added to the reaction mixture in the absence of serum and albumin. In the rat adipose tissue there appeared to be a triglyceride lipase measurable with this assay in addition to the two previously defined lipases, lipoprotein lipase [EC 3.1.1.34] and hormone-sensitive lipase. The enzyme was active in the absence of serum and was strongly inhibited by albumin. The molecular weight was estimated to be about 42,000. Adenosine 3',5'-monophosphate-dependent protein kinase [EC 2.7.1.27] was unable to activate the enzyme. The three species of lipases mentioned above behaved differently upon chromatography on a Sepharose 4B column, and were distinguishable from each other in their physical and kinetic properties. The physiological roles of the new species of lipase remain to be explored.", "contents": "Studies on triglyceride lipases from rat adipose tissue. A new assay procedure for triglyceride lipase [EC 3.1.1.3] was developed in which radioactive triolein was dissolved in ethanol and directly added to the reaction mixture in the absence of serum and albumin. In the rat adipose tissue there appeared to be a triglyceride lipase measurable with this assay in addition to the two previously defined lipases, lipoprotein lipase [EC 3.1.1.34] and hormone-sensitive lipase. The enzyme was active in the absence of serum and was strongly inhibited by albumin. The molecular weight was estimated to be about 42,000. Adenosine 3',5'-monophosphate-dependent protein kinase [EC 2.7.1.27] was unable to activate the enzyme. The three species of lipases mentioned above behaved differently upon chromatography on a Sepharose 4B column, and were distinguishable from each other in their physical and kinetic properties. The physiological roles of the new species of lipase remain to be explored."}
{"id": "PMID:12146", "title": "Purification and properties of oxytocinase (cystine amino-peptidase) from monkey placenta.", "content": "Oxytocinase (cystyl-aminopeptidase) [EC 3.4.11.3] was isolated from monkey placenta in a purified form by a six-step prodedure comprising extraction from monkey placenta homogenate, ammonium sulfate fractionation, repeated chromatography on hydroxylapatite, chromatography on a column of DEAE-cellulose and gel filtration on a column of Sephadex G-200. The purified enzyme showed a single band on polyacrylamide disc electrophoresis. Oxytocin was inactivated by this enzyme preparation. The enzyme hydrolyzed several aminoacyl-beta-naphthylamides. A terminal amino group was required for enzyme activity. The molecular weight of the purified enzyme was estimated to be 87,000 by gel filtration and 83,000 by sodium dodecyl sulfate gel electrophoresis. Other properties of the enzyme, the effects of metal ions and various chemical reagents on the enzyme activity, the pH optimum, and Km values for a number of aminoacyl-beta-naphthylamides were also examined.", "contents": "Purification and properties of oxytocinase (cystine amino-peptidase) from monkey placenta. Oxytocinase (cystyl-aminopeptidase) [EC 3.4.11.3] was isolated from monkey placenta in a purified form by a six-step prodedure comprising extraction from monkey placenta homogenate, ammonium sulfate fractionation, repeated chromatography on hydroxylapatite, chromatography on a column of DEAE-cellulose and gel filtration on a column of Sephadex G-200. The purified enzyme showed a single band on polyacrylamide disc electrophoresis. Oxytocin was inactivated by this enzyme preparation. The enzyme hydrolyzed several aminoacyl-beta-naphthylamides. A terminal amino group was required for enzyme activity. The molecular weight of the purified enzyme was estimated to be 87,000 by gel filtration and 83,000 by sodium dodecyl sulfate gel electrophoresis. Other properties of the enzyme, the effects of metal ions and various chemical reagents on the enzyme activity, the pH optimum, and Km values for a number of aminoacyl-beta-naphthylamides were also examined."}
{"id": "PMID:12147", "title": "Isolation of myosin from starfish sperm heads.", "content": "Myosin was extracted and partially purified from the head portion of spermatozoa of the starfish, Asterias amurensis. The sperm myosin showed a specific Ca2+-activated ATPase [EC 3.6.1.3] activity of 0.2 mumoles Pi/min/mg at high ionic strength and pH 6.5. It resembled egg myosin in forming thick filaments, becoming attached to actin filaments. subunit composition, and serological properties.", "contents": "Isolation of myosin from starfish sperm heads. Myosin was extracted and partially purified from the head portion of spermatozoa of the starfish, Asterias amurensis. The sperm myosin showed a specific Ca2+-activated ATPase [EC 3.6.1.3] activity of 0.2 mumoles Pi/min/mg at high ionic strength and pH 6.5. It resembled egg myosin in forming thick filaments, becoming attached to actin filaments. subunit composition, and serological properties."}
{"id": "PMID:12148", "title": "A clottable protein (coagulogen) from amoebocyte lysate of Japanese horseshoe crab (Tachypleus tridentatus). Its isolation and biochemical properties.", "content": "A clottable protein, named coagulogen, was highly purified from the amoebocyte lysate of Japanese horseshoe crab (Tachypleus tridentatus) by a method similar to that used for the lysate of Limulus polyphemus amoebocytes. The isolated material gave a single protein band on analytical gel electrophoresis at pH 3.2, gel electrofocusing, and sodium dodecyl sulfate (SDS) gel electrophoresis with or without 2-mercaptoethanol. It was 90 percent coagulable, and the total yield from 10 ml of the amoebocyte lysate was about 40 mg. The sedimentation coefficient of purified coagulogen was 2.6 S and its molecular weight was estimated to be about 15,300 by sedimentation equilibrium analysis. The molecular weight estimated by SDS-gel electrophoretic analysis was 19,500 +/- 1,000. This discrepancy was apparently due to abnormal mobility arising from the basic nature of this protein on electrophoresis. The protein had a high isoelectric point of pH 10.0 +/- 0.2, as measured by the isoelectric focusing technique. It consisted of a total of 132 to 135 amino acid residues and contained high levels of basic amino acids, which accounted for more than 16 per cent of the total amino acid residues. No methionine was detected. High contents of valine, half-cystine, glutamic acid (glutamine), and phenylalanine were found. The N-terminal sequence of the first three residues of the coagulogen was Ala-Asx-Thr, and its C-terminal residues was identified as phenylalanine, indicating that it consists of a single polypeptide chain. It is of interest that the first three N-terminal residues are homologous with those of the Aalpha-chain of non-human primate fibrinogen.", "contents": "A clottable protein (coagulogen) from amoebocyte lysate of Japanese horseshoe crab (Tachypleus tridentatus). Its isolation and biochemical properties. A clottable protein, named coagulogen, was highly purified from the amoebocyte lysate of Japanese horseshoe crab (Tachypleus tridentatus) by a method similar to that used for the lysate of Limulus polyphemus amoebocytes. The isolated material gave a single protein band on analytical gel electrophoresis at pH 3.2, gel electrofocusing, and sodium dodecyl sulfate (SDS) gel electrophoresis with or without 2-mercaptoethanol. It was 90 percent coagulable, and the total yield from 10 ml of the amoebocyte lysate was about 40 mg. The sedimentation coefficient of purified coagulogen was 2.6 S and its molecular weight was estimated to be about 15,300 by sedimentation equilibrium analysis. The molecular weight estimated by SDS-gel electrophoretic analysis was 19,500 +/- 1,000. This discrepancy was apparently due to abnormal mobility arising from the basic nature of this protein on electrophoresis. The protein had a high isoelectric point of pH 10.0 +/- 0.2, as measured by the isoelectric focusing technique. It consisted of a total of 132 to 135 amino acid residues and contained high levels of basic amino acids, which accounted for more than 16 per cent of the total amino acid residues. No methionine was detected. High contents of valine, half-cystine, glutamic acid (glutamine), and phenylalanine were found. The N-terminal sequence of the first three residues of the coagulogen was Ala-Asx-Thr, and its C-terminal residues was identified as phenylalanine, indicating that it consists of a single polypeptide chain. It is of interest that the first three N-terminal residues are homologous with those of the Aalpha-chain of non-human primate fibrinogen."}
{"id": "PMID:12149", "title": "The mechanism of reassembly of immunoglobulin G.", "content": "The noncovalent interaction of light (L) chain with heavy (H) chain or Fd isolated from a human myeloma protein Jo (IgG1, kappa) was studied by following circular dichroic (CD) change at 235 nm. The dimerization constants of Jo-L chain determined by measuring the CD change at 293 nm with protein concentration showed that the Jo-L chain exists as the monomeric form under the experimental conditions used for recombination with H chain. The second-order rate constants for the interaction between H and L chains were in good agreement with those for the interaction between Fd and L chain at various pH values. The binding behavior of L chain to Fd could be described by a single association constant. In the interpretation of the binding of L chain to H chain, however, it was necessary to assume that the binding of L chain to one of the two sites on H chain dimer (H2) decreases the affinity of the other site for L chain. The binding constant of the first L chain to H2 was the same as that of L chain to Fd. Renaturation processes of L chain, Fd, Fab(SS) fragment (with intact interchain disulfide bond), and Fab(RA) fragment (in which the interchain disulfide bond had been reduced and alkylated) from the denatured states in 0.5 or 1 M acetic acid on neutralization were studied. The renaturation of Fd occurred very rapidly, while that of L chain consisted of a very rapid process and a slow process which followed first-order kinetics. The renaturation process of Fab(SS) consisted of rapid and slow phases, of which the latter followed first-order kinetics. The renaturation process of Fab(RA) also consisted of rapid and slow phases, but the latter process followed second-order kinetics. The overall rate constant of renaturation of Fab(RA) was the same as that of the reformation of Fab(RA) from isolated Fd and L chain. On the basis of these facts, the kinetic mechanism by which Fd and L chain recombine to yield Fab(RA) can be described in terms of the scheme Fd + L in equilibrium Fd ... L leads to Fab(RA), where Fd ... L is an intermediate, and CD change is only observed in the second unimolecular process and not in the first bimolecular process.", "contents": "The mechanism of reassembly of immunoglobulin G. The noncovalent interaction of light (L) chain with heavy (H) chain or Fd isolated from a human myeloma protein Jo (IgG1, kappa) was studied by following circular dichroic (CD) change at 235 nm. The dimerization constants of Jo-L chain determined by measuring the CD change at 293 nm with protein concentration showed that the Jo-L chain exists as the monomeric form under the experimental conditions used for recombination with H chain. The second-order rate constants for the interaction between H and L chains were in good agreement with those for the interaction between Fd and L chain at various pH values. The binding behavior of L chain to Fd could be described by a single association constant. In the interpretation of the binding of L chain to H chain, however, it was necessary to assume that the binding of L chain to one of the two sites on H chain dimer (H2) decreases the affinity of the other site for L chain. The binding constant of the first L chain to H2 was the same as that of L chain to Fd. Renaturation processes of L chain, Fd, Fab(SS) fragment (with intact interchain disulfide bond), and Fab(RA) fragment (in which the interchain disulfide bond had been reduced and alkylated) from the denatured states in 0.5 or 1 M acetic acid on neutralization were studied. The renaturation of Fd occurred very rapidly, while that of L chain consisted of a very rapid process and a slow process which followed first-order kinetics. The renaturation process of Fab(SS) consisted of rapid and slow phases, of which the latter followed first-order kinetics. The renaturation process of Fab(RA) also consisted of rapid and slow phases, but the latter process followed second-order kinetics. The overall rate constant of renaturation of Fab(RA) was the same as that of the reformation of Fab(RA) from isolated Fd and L chain. On the basis of these facts, the kinetic mechanism by which Fd and L chain recombine to yield Fab(RA) can be described in terms of the scheme Fd + L in equilibrium Fd ... L leads to Fab(RA), where Fd ... L is an intermediate, and CD change is only observed in the second unimolecular process and not in the first bimolecular process."}
{"id": "PMID:12150", "title": "Interaction between D-amino acid oxidase and small molecules.", "content": "1. From the standpoint of monomer-dimer equilibrium of hog kidney D-amino acid oxidase [EC 1.4.3.3] and the interaction between the enzyme and small molecules, the effect of pH on the binding of p-aminobenzoate to the monomer and dimer of the enzyme was studied by kinetic methods and spectrophotometric titration. 2. The maximum binding number of p-aminobenzoate to the dimer is two molecules, and there is no interaction between the two active sites of the dimer (i.e., no cooperativity) over the range of pH from 6.5 to 10. 3. The affinity of the dimer for p-aminobenzoate is several times higher than that of the monomer at pH 6.5-10, and consequently p-aminobenzoate induces dimerization in the equilibrium state of D-amino acid oxidase. The interaction energy of two subunits of the dimer is stabilized by the binding of p-aminobenzoate by 1-2 kcal/mole over the pH range studied. 4. The binding sites of the quasi-substrate, p-aminobenzoate, in the dimer and the intersubunit binding site of the dimer are clearly different, because p-aminobenzoate induces dimerization of the enzyme. 5. The pK values of ionizing groups in the free monomer and the free dimer which participate in the binding of the competitive inhibitor, p-aminobenzoate, are approximately the same, 8.7, as determined from the pH dependence of the affinity of the inhibitor for the enzyme. Furthermore, no pK for the enzyme-inhibitor complex in the pH range 6.5-10 was observed. 6. There is no interaction between the two ionizing groups of the dimer during protonation-deprotonation, because a theoretical equation involving no cooperativity between the two ionizing groups in the dimer explains the results well.", "contents": "Interaction between D-amino acid oxidase and small molecules. 1. From the standpoint of monomer-dimer equilibrium of hog kidney D-amino acid oxidase [EC 1.4.3.3] and the interaction between the enzyme and small molecules, the effect of pH on the binding of p-aminobenzoate to the monomer and dimer of the enzyme was studied by kinetic methods and spectrophotometric titration. 2. The maximum binding number of p-aminobenzoate to the dimer is two molecules, and there is no interaction between the two active sites of the dimer (i.e., no cooperativity) over the range of pH from 6.5 to 10. 3. The affinity of the dimer for p-aminobenzoate is several times higher than that of the monomer at pH 6.5-10, and consequently p-aminobenzoate induces dimerization in the equilibrium state of D-amino acid oxidase. The interaction energy of two subunits of the dimer is stabilized by the binding of p-aminobenzoate by 1-2 kcal/mole over the pH range studied. 4. The binding sites of the quasi-substrate, p-aminobenzoate, in the dimer and the intersubunit binding site of the dimer are clearly different, because p-aminobenzoate induces dimerization of the enzyme. 5. The pK values of ionizing groups in the free monomer and the free dimer which participate in the binding of the competitive inhibitor, p-aminobenzoate, are approximately the same, 8.7, as determined from the pH dependence of the affinity of the inhibitor for the enzyme. Furthermore, no pK for the enzyme-inhibitor complex in the pH range 6.5-10 was observed. 6. There is no interaction between the two ionizing groups of the dimer during protonation-deprotonation, because a theoretical equation involving no cooperativity between the two ionizing groups in the dimer explains the results well."}
{"id": "PMID:12151", "title": "A study of the interaction between D-amino acid oxidase and quasi-substrates.", "content": "To study the interaction between D-amino acid oxidase [EC 1.4.3.3] and quasi-substrates such as benzoate and o-, m-, and p-aminobenzoate, visible circular dichroism spectra (CD spectra) were measured and the binding rate and affinity of o-aminobenzoate to the enzyme were observed by following the absorption changes at various wavelengths. We found a new CD band around 560 nm, corresponding to the charge-transfer complexes which result from the formation of aminobenzoate complexes with the enzyme. The ellipticity of this band was positive for the p-aminobenzoate complex, but negative for the o- and m-aminobenzoate complexes. Crossover points in CD spectra were observed at 470 nm for the m-aminobenzoate complex and at 475 nm for the o-aminobenzoate complex. They probably resulted from overlapping of the positive CD band of FAD bound with the enzyme and the negative CD band of the charge-transfer complex. We propose that the amino group in aminobenzoate, not the pi-electrons of the benzene ring, is the electron donor in the charge-transfer complex and that the position of the amino group is very important for the charge-transfer interaction. The binding rate and affinity of o-aminobenzoate to the enzyme were determined using the absorption changes at 370 nm (380 nm), caused by the modification of electronic states of FAD bound with the enzyme, and at 550 nm (565 nm), caused by the formation of the charge-transfer complex of o-aminobenzoate with the enzyme. No differences between these parameters with wavelength were observed. This independence of wavelength simplifies discussion of the experimental data obtained from absorption changes.", "contents": "A study of the interaction between D-amino acid oxidase and quasi-substrates. To study the interaction between D-amino acid oxidase [EC 1.4.3.3] and quasi-substrates such as benzoate and o-, m-, and p-aminobenzoate, visible circular dichroism spectra (CD spectra) were measured and the binding rate and affinity of o-aminobenzoate to the enzyme were observed by following the absorption changes at various wavelengths. We found a new CD band around 560 nm, corresponding to the charge-transfer complexes which result from the formation of aminobenzoate complexes with the enzyme. The ellipticity of this band was positive for the p-aminobenzoate complex, but negative for the o- and m-aminobenzoate complexes. Crossover points in CD spectra were observed at 470 nm for the m-aminobenzoate complex and at 475 nm for the o-aminobenzoate complex. They probably resulted from overlapping of the positive CD band of FAD bound with the enzyme and the negative CD band of the charge-transfer complex. We propose that the amino group in aminobenzoate, not the pi-electrons of the benzene ring, is the electron donor in the charge-transfer complex and that the position of the amino group is very important for the charge-transfer interaction. The binding rate and affinity of o-aminobenzoate to the enzyme were determined using the absorption changes at 370 nm (380 nm), caused by the modification of electronic states of FAD bound with the enzyme, and at 550 nm (565 nm), caused by the formation of the charge-transfer complex of o-aminobenzoate with the enzyme. No differences between these parameters with wavelength were observed. This independence of wavelength simplifies discussion of the experimental data obtained from absorption changes."}
{"id": "PMID:12152", "title": "Physiological significance of Ca uptake by mitochondria in the heart in comparison with that by cardiac sarcoplasmic reticulum.", "content": "It was investigated whether mitochondria play a significant role in the physiological regulation of the contractile process by Ca2+ in cardiac muscle in comparison with the sarcoplasmic reticulum (SR). Ca uptake activities of chicken cardiac SR and rabbit cardiac mitochondria were measured by means of centrifugation, dual-wave-length spectrophotometric and Millipore filtration methods. The maximum Ca uptake capacity of cardiac SR was usually 50-60 nmoles/mg protein and the apparent binding constant was 2.0 X 10(6) M-1. The apparent Ca-binding constant of cardiac mitochondria under limited loading conditions was 2.4 X 10(5) M-1 at pH 7.4 and 5.9 X 10(4) M-1 at pH 6.8. In the presence of 100 muM Ca2+ at 28-29 degrees, the estimated initial rate of Ca uptake of cardiac SR ranged from 20 to 30 nmoles Ca/mg-sec, while that of mitochondria was 4.6 nmoles Ca/mg-sec under limited loading conditions at pH 7.4 and 0.64 nmoles Ca/mg-sec under massive loading conditions at pH 6.8, which was much closer to physiological conditions. In the presence of low Ca2+ concentrations, the initial rate of Ca uptake of cardiac SR was 0.5 nmoles Ca/mg-sec at 3.5 X 10(-7) M Ca2+ and that of mitochondria under massive loading conditions at 1 X 10(-6) M Ca2+ was 0.02 nmoles Ca/mg-sec at pH 7.4 and 0.004 nmoles Ca/mg-sec at pH 6.8. The Ca uptake activities were also examined using glycerol-extracted cardiac muscle fibers. Cardiac SR, 1.7 mg/ml, reduced the tension of maximally contracted cardiac muscle fibers to a level corresponding to about 30% of maximum tension, but in the presence of 14.3 mg/ml of mitochondria the maximum tensions of both skeletal muscle and cardiac muscle fibers were maintained for at least 3 min. From these results the time course of relaxation of cardiac muscle induced by cardiac SR or mitochondria was calculated. It was concluded that, in the physiological contraction of cardiac muscle, the SR plays a major role in controlling intracellular Ca2+ movement; the Ca uptake of mitochondria is relatively insignificant. When the cardiac muscle contracts maximally, SR alone cannot relax the cardiac muscle without the aid of other Ca removing system.", "contents": "Physiological significance of Ca uptake by mitochondria in the heart in comparison with that by cardiac sarcoplasmic reticulum. It was investigated whether mitochondria play a significant role in the physiological regulation of the contractile process by Ca2+ in cardiac muscle in comparison with the sarcoplasmic reticulum (SR). Ca uptake activities of chicken cardiac SR and rabbit cardiac mitochondria were measured by means of centrifugation, dual-wave-length spectrophotometric and Millipore filtration methods. The maximum Ca uptake capacity of cardiac SR was usually 50-60 nmoles/mg protein and the apparent binding constant was 2.0 X 10(6) M-1. The apparent Ca-binding constant of cardiac mitochondria under limited loading conditions was 2.4 X 10(5) M-1 at pH 7.4 and 5.9 X 10(4) M-1 at pH 6.8. In the presence of 100 muM Ca2+ at 28-29 degrees, the estimated initial rate of Ca uptake of cardiac SR ranged from 20 to 30 nmoles Ca/mg-sec, while that of mitochondria was 4.6 nmoles Ca/mg-sec under limited loading conditions at pH 7.4 and 0.64 nmoles Ca/mg-sec under massive loading conditions at pH 6.8, which was much closer to physiological conditions. In the presence of low Ca2+ concentrations, the initial rate of Ca uptake of cardiac SR was 0.5 nmoles Ca/mg-sec at 3.5 X 10(-7) M Ca2+ and that of mitochondria under massive loading conditions at 1 X 10(-6) M Ca2+ was 0.02 nmoles Ca/mg-sec at pH 7.4 and 0.004 nmoles Ca/mg-sec at pH 6.8. The Ca uptake activities were also examined using glycerol-extracted cardiac muscle fibers. Cardiac SR, 1.7 mg/ml, reduced the tension of maximally contracted cardiac muscle fibers to a level corresponding to about 30% of maximum tension, but in the presence of 14.3 mg/ml of mitochondria the maximum tensions of both skeletal muscle and cardiac muscle fibers were maintained for at least 3 min. From these results the time course of relaxation of cardiac muscle induced by cardiac SR or mitochondria was calculated. It was concluded that, in the physiological contraction of cardiac muscle, the SR plays a major role in controlling intracellular Ca2+ movement; the Ca uptake of mitochondria is relatively insignificant. When the cardiac muscle contracts maximally, SR alone cannot relax the cardiac muscle without the aid of other Ca removing system."}
{"id": "PMID:12153", "title": "Enzymatic studies on a cellulase system of Trichoderma viride. IV. Purification and properties of a less-random type cellulase.", "content": "A cellulase [EC 3.2.1.4] component was purified from a crude cellulase preparation of Trichoderma viride (Meicelase) by consecutive column chromatography procedures, and was designated as cellulase III. The enzyme was homogeneous on polyacrylamide gel disc electrophoresis. The molecular weight of the enzyme was estimated to be about 45,000 by gel filtration. The optimum pH and temperature of the enzyme were pH 4.5-5.0 and 50 degrees, respectively. The enzyme was stable over the range of pH 4.5-7.5 at 4 degrees for 24 hr, and retained 40% of the original carboxymethylcellulose-saccharifying activity after heating at 100 degrees for 10 min. The enzyme was completely inactivated by 1 mM Hg2+, and partially by 1 mM Ag+ and Cu2+. The enzyme was characterized as a less-random type cellulase on the basis of its action on carboxymethylcellulose. The enzyme split cellohexaose, retaining the beta-configuration of the anomeric carbon atoms in the hydrolysis products. The Km values of cellulase III for cellooligosaccharides decreased in parallel with increase of the chain length of the substrates, while Vmax values showed a tendency to increase. The enzyme produced predominantly cellobiose and glucose from various cellulosic substrates as well as from higher cellooligosaccharides. Cellulase III preferentially attacked the aglycone linkage of p-nitrophenyl beta-D-cellobioside. The enzyme was found to catalyze the rapid synthesis of cellotetraose from cellobiose (condensation action).", "contents": "Enzymatic studies on a cellulase system of Trichoderma viride. IV. Purification and properties of a less-random type cellulase. A cellulase [EC 3.2.1.4] component was purified from a crude cellulase preparation of Trichoderma viride (Meicelase) by consecutive column chromatography procedures, and was designated as cellulase III. The enzyme was homogeneous on polyacrylamide gel disc electrophoresis. The molecular weight of the enzyme was estimated to be about 45,000 by gel filtration. The optimum pH and temperature of the enzyme were pH 4.5-5.0 and 50 degrees, respectively. The enzyme was stable over the range of pH 4.5-7.5 at 4 degrees for 24 hr, and retained 40% of the original carboxymethylcellulose-saccharifying activity after heating at 100 degrees for 10 min. The enzyme was completely inactivated by 1 mM Hg2+, and partially by 1 mM Ag+ and Cu2+. The enzyme was characterized as a less-random type cellulase on the basis of its action on carboxymethylcellulose. The enzyme split cellohexaose, retaining the beta-configuration of the anomeric carbon atoms in the hydrolysis products. The Km values of cellulase III for cellooligosaccharides decreased in parallel with increase of the chain length of the substrates, while Vmax values showed a tendency to increase. The enzyme produced predominantly cellobiose and glucose from various cellulosic substrates as well as from higher cellooligosaccharides. Cellulase III preferentially attacked the aglycone linkage of p-nitrophenyl beta-D-cellobioside. The enzyme was found to catalyze the rapid synthesis of cellotetraose from cellobiose (condensation action)."}
{"id": "PMID:12154", "title": "Metabolism of triacylglycerol in Mycobacterium smegmatis.", "content": "Mycobacterium smegmatis cells incorporated [1-14C]oleic acid into triacylglycerols (TG) from the medium more rapidly than shorter chain fatty acids, caprilic and butyric acids. This incorporation was inhibited more strongly by 10(-3) M N-ethylmaleimide than by 10(-3) M KCN. [14C]TG in the bacterial cells was utilized when the cells were in poor nutritional conditions, such as phosphate buffer (pH 7.0) containing oleic acid. Accumulation of TG was observed in the cells at late stages of growth. Diglyceride acyltransferase [EC 2.3.1.20] activity was detected in a cell-free extract from this bacterium. The pH optimum of this enzyme was between pH 7 and 9. F- and Tween 20 showed remarkable enhancing and inhibitory effects, respectively.", "contents": "Metabolism of triacylglycerol in Mycobacterium smegmatis. Mycobacterium smegmatis cells incorporated [1-14C]oleic acid into triacylglycerols (TG) from the medium more rapidly than shorter chain fatty acids, caprilic and butyric acids. This incorporation was inhibited more strongly by 10(-3) M N-ethylmaleimide than by 10(-3) M KCN. [14C]TG in the bacterial cells was utilized when the cells were in poor nutritional conditions, such as phosphate buffer (pH 7.0) containing oleic acid. Accumulation of TG was observed in the cells at late stages of growth. Diglyceride acyltransferase [EC 2.3.1.20] activity was detected in a cell-free extract from this bacterium. The pH optimum of this enzyme was between pH 7 and 9. F- and Tween 20 showed remarkable enhancing and inhibitory effects, respectively."}
{"id": "PMID:12155", "title": "Hydrogen-deuterium exchange in the histidine residues of bovine alpha-lactalbumin.", "content": "The proton magnetic resonance spectrum of bovine alpha-lactalbumin has been observed, and three peaks assignable to the position-2 CH protons of the three histidine rpsidues (His 32, 68, and 107) of this protein have been subjected to detailed examination. The assignments of these peaks to His 32, 68, and 107 were made on the basis of the difference in their reactivities with iodoacetic acid. The rate constants of the hydrogen-deuterium exchange reactions were found to be 8.0 X 10(-5), 2.6 X 10(-4), and 8.0 X 10(-5) min-1, respectively, at pH 8.5 and at 35 degrees, while at 62 degrees all three were found to be 0.84 approximately 1.1 X 10(-2) min-1. On the basis of these data, it has been shown that, in the native form of this protein, His 68 is the most exposed to the solvent while His 32 and His 107 are buried slightly deeper in the surface of the molecule. The fluctuation amplitudes gamma, or the effective chances of His 32, 68, and 107 to be fully exposed to the solvent, were found to be 0.4, 1.3, and 0.4, respectively.", "contents": "Hydrogen-deuterium exchange in the histidine residues of bovine alpha-lactalbumin. The proton magnetic resonance spectrum of bovine alpha-lactalbumin has been observed, and three peaks assignable to the position-2 CH protons of the three histidine rpsidues (His 32, 68, and 107) of this protein have been subjected to detailed examination. The assignments of these peaks to His 32, 68, and 107 were made on the basis of the difference in their reactivities with iodoacetic acid. The rate constants of the hydrogen-deuterium exchange reactions were found to be 8.0 X 10(-5), 2.6 X 10(-4), and 8.0 X 10(-5) min-1, respectively, at pH 8.5 and at 35 degrees, while at 62 degrees all three were found to be 0.84 approximately 1.1 X 10(-2) min-1. On the basis of these data, it has been shown that, in the native form of this protein, His 68 is the most exposed to the solvent while His 32 and His 107 are buried slightly deeper in the surface of the molecule. The fluctuation amplitudes gamma, or the effective chances of His 32, 68, and 107 to be fully exposed to the solvent, were found to be 0.4, 1.3, and 0.4, respectively."}
{"id": "PMID:12156", "title": "The structure and function of acid proteases. VI. Effects of acid protease-specific inhibitors on the acid proteases from Aspergillus niger var. macrosporus.", "content": "1. The Type B acid protease from Aspergillus niger var. macrosporus was inactivated by reaction with diazoacetyl-DL-norleucine methyl ester (DAN), DL-1-diazo-3-tosylamido-2-heptanone (DTH), and L-1-diazo-3-tosylamido-4-phenyl-2-butanone (DTPB) in the presence of cupric ions. The reaction with DAN took place with 1:1 stoichiometry. The enzyme was also inactivated by reaction with 1, 2-epoxy-3-(p-nitrophenoxy)-propane (EPNP) with concomitant incorporation of approximately two EPNP molecules per molecule of protein. Moreover, these reactions of DAN and of EPNP were markedly inhibited by pepstatin. These results seem to indicate that, as in the case of porcine pepsin [EC 3.4.23.1] and related acid proteases, the enzyme has two essential carboxyl groups at the active site, one reactive with DAN and related diazo reagents in the presence of cupric ions and the other reactive with EPNP, and that pepstatin binds in the vicinity of these residues. 2. The Type A acid protease from the same mold, on the other hand, was found to be markedly less sensitive to these specific inhibitors. Under conditions where the Type B enzyme was completely inactivated by DAN and related diazo reagents, only partial inactivation of this enzyme occurred. The effect of prior mixing of DAN and cupric ions on the pH profile of inactivation was also different from that for the Type B enzyme. Moreover, the Type A enzyme was not inactivated by EPNP. These results thus indicate that the nature of the active site of the Type A enzyme is rather different from that of the Type B enzyme and hence that the Type A enzyme belongs to a different class of acid proteases from the Type B enzyme.", "contents": "The structure and function of acid proteases. VI. Effects of acid protease-specific inhibitors on the acid proteases from Aspergillus niger var. macrosporus. 1. The Type B acid protease from Aspergillus niger var. macrosporus was inactivated by reaction with diazoacetyl-DL-norleucine methyl ester (DAN), DL-1-diazo-3-tosylamido-2-heptanone (DTH), and L-1-diazo-3-tosylamido-4-phenyl-2-butanone (DTPB) in the presence of cupric ions. The reaction with DAN took place with 1:1 stoichiometry. The enzyme was also inactivated by reaction with 1, 2-epoxy-3-(p-nitrophenoxy)-propane (EPNP) with concomitant incorporation of approximately two EPNP molecules per molecule of protein. Moreover, these reactions of DAN and of EPNP were markedly inhibited by pepstatin. These results seem to indicate that, as in the case of porcine pepsin [EC 3.4.23.1] and related acid proteases, the enzyme has two essential carboxyl groups at the active site, one reactive with DAN and related diazo reagents in the presence of cupric ions and the other reactive with EPNP, and that pepstatin binds in the vicinity of these residues. 2. The Type A acid protease from the same mold, on the other hand, was found to be markedly less sensitive to these specific inhibitors. Under conditions where the Type B enzyme was completely inactivated by DAN and related diazo reagents, only partial inactivation of this enzyme occurred. The effect of prior mixing of DAN and cupric ions on the pH profile of inactivation was also different from that for the Type B enzyme. Moreover, the Type A enzyme was not inactivated by EPNP. These results thus indicate that the nature of the active site of the Type A enzyme is rather different from that of the Type B enzyme and hence that the Type A enzyme belongs to a different class of acid proteases from the Type B enzyme."}
{"id": "PMID:12157", "title": "Pepsinogen C and pepsin C from gastric mucosa of Japanese monkey. Purification and characterization.", "content": "A new pepsinogen component, pepsinogen C, was purified from the gastric mucosa of Japanese monkey. The chromatographic behavior of this component on DE-32 cellulose was coincident with that of pepsinogen III-2 previously reported (1), and final purification was performed by large-scale polyacrylamide disc gel electrophoresis. The molecular weight was 35,000 as determined by gel filtration. The ratios of glutamic acid to aspartic acid and of leucine to isoleucine were higher than those of other Japanese monkey pepsinogens. The activated form, pepsin C, had a molecular weight of 27,000 and contained a large number of glutamic acid residues. The optimal pH for hemoglobin digestion was 3.0. Pepsin C could scarcely hydrolyze the synthetic substrate, N-acetyl-L-phenylalanyl-3, 5-diiodo-L-tyrosine (APDT). 1, 2-Epoxy-3-(p-nitrophenoxy)propane (EPNP), p-bromophenacyl bromide, and diazoacetyl-DL-norleucine methyl ester (DAN) inhibited pepsin C [EC 3.4.23.3] in the same way as pepsin III-3 of Japanese monkey. The susceptibility to pepstatin of pepsin C was lower than that of pepsin III-3, and 500 times more pepstatin was required for the same inhibitory effect. The classification and nomenclature of Japanese monkey pepsinogens and pepsins are discussed.", "contents": "Pepsinogen C and pepsin C from gastric mucosa of Japanese monkey. Purification and characterization. A new pepsinogen component, pepsinogen C, was purified from the gastric mucosa of Japanese monkey. The chromatographic behavior of this component on DE-32 cellulose was coincident with that of pepsinogen III-2 previously reported (1), and final purification was performed by large-scale polyacrylamide disc gel electrophoresis. The molecular weight was 35,000 as determined by gel filtration. The ratios of glutamic acid to aspartic acid and of leucine to isoleucine were higher than those of other Japanese monkey pepsinogens. The activated form, pepsin C, had a molecular weight of 27,000 and contained a large number of glutamic acid residues. The optimal pH for hemoglobin digestion was 3.0. Pepsin C could scarcely hydrolyze the synthetic substrate, N-acetyl-L-phenylalanyl-3, 5-diiodo-L-tyrosine (APDT). 1, 2-Epoxy-3-(p-nitrophenoxy)propane (EPNP), p-bromophenacyl bromide, and diazoacetyl-DL-norleucine methyl ester (DAN) inhibited pepsin C [EC 3.4.23.3] in the same way as pepsin III-3 of Japanese monkey. The susceptibility to pepstatin of pepsin C was lower than that of pepsin III-3, and 500 times more pepstatin was required for the same inhibitory effect. The classification and nomenclature of Japanese monkey pepsinogens and pepsins are discussed."}
{"id": "PMID:12158", "title": "[Dissolution kinetics of synthetic hydroxyapatite and human enamel crystals].", "content": "A comparative study of the dissolution of synthetic hydroxyapatite and human enamel crystals has been realized in a buffered (sodium citrate - citric acid) solution in presence of variable quantities of sodium fluoride. The pH of the solutions used was 3.7 and 5.6. The dissolution curves of the synthetic hydroxyapatite and the human enamel crystals were similar. In all cases, the dissolution mechanism was characterized by a first step with a rapid kinetic corresponding to the formation of a central cavity extending parallel to the c axis of the apatite crystal and observed with the electron microscope. In a second stage, the dissolution kinetic was much slower corresponding to a saturation of the buffered solution and an extension of the crystal destruction towards its lateral external surfaces. The dissolution kinetic was faster in a more acidic solution and the total dissolution at a given moment varied inversely to the fluoride amount.", "contents": "[Dissolution kinetics of synthetic hydroxyapatite and human enamel crystals]. A comparative study of the dissolution of synthetic hydroxyapatite and human enamel crystals has been realized in a buffered (sodium citrate - citric acid) solution in presence of variable quantities of sodium fluoride. The pH of the solutions used was 3.7 and 5.6. The dissolution curves of the synthetic hydroxyapatite and the human enamel crystals were similar. In all cases, the dissolution mechanism was characterized by a first step with a rapid kinetic corresponding to the formation of a central cavity extending parallel to the c axis of the apatite crystal and observed with the electron microscope. In a second stage, the dissolution kinetic was much slower corresponding to a saturation of the buffered solution and an extension of the crystal destruction towards its lateral external surfaces. The dissolution kinetic was faster in a more acidic solution and the total dissolution at a given moment varied inversely to the fluoride amount."}
{"id": "PMID:12159", "title": "Human epidermal transglutaminase. Preparation and properties.", "content": "A transglutaminase from human hair follicle-free epidermis was purified to homogeneity using gel filtration and ion exchange chromatography. The enzyme had an apparent Mr = 51,000 +/- 2,000 by sodium dodecyl sulfate electrophoresis, 100,000 +/- 5,000 by discontinuous gel electrophoresis, and 50,000 +/- 2,000 by gel filtration in Bio-Gel A-0.5m agarose. The enzyme cross-linked Factor XIII-free fibrinogen forming gamma dimers and alpha polymers. Either calcium or strontium was necessary for enzyme activity. In the presence of calcium, enzyme activity was increased by heating at 56 degrees or by treating with dimethylsulfoxide. Activation required calcium and occurred in the presence of serine protease inhibitors. The activated and native enzyme had apparently identical mobilities in acrylamide disc electrophoresis and sodium dodecyl sulfate electrophoresis. The Km values for two substrates in the reaction, casein and putrescine, were very similar for the native and the activated enzyme. The activated enzyme had a larger elution volume on Bio-Gel A-0.5m in the presence of calcium than did the native enzyme. The detailed mechanism of activation remains to be determined.", "contents": "Human epidermal transglutaminase. Preparation and properties. A transglutaminase from human hair follicle-free epidermis was purified to homogeneity using gel filtration and ion exchange chromatography. The enzyme had an apparent Mr = 51,000 +/- 2,000 by sodium dodecyl sulfate electrophoresis, 100,000 +/- 5,000 by discontinuous gel electrophoresis, and 50,000 +/- 2,000 by gel filtration in Bio-Gel A-0.5m agarose. The enzyme cross-linked Factor XIII-free fibrinogen forming gamma dimers and alpha polymers. Either calcium or strontium was necessary for enzyme activity. In the presence of calcium, enzyme activity was increased by heating at 56 degrees or by treating with dimethylsulfoxide. Activation required calcium and occurred in the presence of serine protease inhibitors. The activated and native enzyme had apparently identical mobilities in acrylamide disc electrophoresis and sodium dodecyl sulfate electrophoresis. The Km values for two substrates in the reaction, casein and putrescine, were very similar for the native and the activated enzyme. The activated enzyme had a larger elution volume on Bio-Gel A-0.5m in the presence of calcium than did the native enzyme. The detailed mechanism of activation remains to be determined."}
{"id": "PMID:12160", "title": "Activation of soluble guanylate cyclase from rat lung by incubation or by hydrogen peroxide.", "content": "A 37,000 X g supernatant fraction prepared from fat lung homogenate demonstrated a 2- to 3-fold increase in guanylate cyclase activity after incubation at 30 degrees for 30 min (preincubation). Treatment of the supernatant fraction with Triton X-100 increased activity to approximately the same extent as preincubation, but would not increase the activity after preincubation. By chromatography on Sepharose 2B, before and after preincubation, it was demonstrated that the increase in activity was only associated with the soluble guanylate cyclase, and not the particulate enzyme. Activation by preincubation required O2. It was completely inhibited by thiols such as 2-mercaptoethanol, and by bovine serum albumin, KCN, and sodium diethyldithiocarbamate. These inhibitors suggested a copper requirement for activation, and this was confirmed by demonstrating that 20 to 60 muM CuCl2 could relieve the inhibition by 0.1 mM sodium diethyldithiocarbamate. 2-Mercaptoethanol inhibition could also be reversed by removal of the thiol on a Sephadex G-25 column, however, this treatment partially activated the enzyme. Addition of 2-mercaptoethanol to a preincubated preparation would not reverse the activation. H2O2 was found to activate guanylate cyclase, either by its generation in the lung supernatant with glucose oxidase and glucose, or by its addition to a preparation in which the catalase was inhibited with KCN. KCN or bovine serum albumin was able to partially inhibit activation by glucose oxidase plus glucose, however, larger amounts of glucose oxidase could overcome that inhibition, indicating a catalytic role for Cu2+ at low H2O2 concentrations. No direct evidence for H2O2 formation during preincubation could be found, however, indirect evidence was obtained by the spectrophotometric detection of choleglobin formation from hemoglobin present in the lung supernatant fluid. The H2O2 is believed to result from the reaction of oxyhemoglobin with ascorbate.", "contents": "Activation of soluble guanylate cyclase from rat lung by incubation or by hydrogen peroxide. A 37,000 X g supernatant fraction prepared from fat lung homogenate demonstrated a 2- to 3-fold increase in guanylate cyclase activity after incubation at 30 degrees for 30 min (preincubation). Treatment of the supernatant fraction with Triton X-100 increased activity to approximately the same extent as preincubation, but would not increase the activity after preincubation. By chromatography on Sepharose 2B, before and after preincubation, it was demonstrated that the increase in activity was only associated with the soluble guanylate cyclase, and not the particulate enzyme. Activation by preincubation required O2. It was completely inhibited by thiols such as 2-mercaptoethanol, and by bovine serum albumin, KCN, and sodium diethyldithiocarbamate. These inhibitors suggested a copper requirement for activation, and this was confirmed by demonstrating that 20 to 60 muM CuCl2 could relieve the inhibition by 0.1 mM sodium diethyldithiocarbamate. 2-Mercaptoethanol inhibition could also be reversed by removal of the thiol on a Sephadex G-25 column, however, this treatment partially activated the enzyme. Addition of 2-mercaptoethanol to a preincubated preparation would not reverse the activation. H2O2 was found to activate guanylate cyclase, either by its generation in the lung supernatant with glucose oxidase and glucose, or by its addition to a preparation in which the catalase was inhibited with KCN. KCN or bovine serum albumin was able to partially inhibit activation by glucose oxidase plus glucose, however, larger amounts of glucose oxidase could overcome that inhibition, indicating a catalytic role for Cu2+ at low H2O2 concentrations. No direct evidence for H2O2 formation during preincubation could be found, however, indirect evidence was obtained by the spectrophotometric detection of choleglobin formation from hemoglobin present in the lung supernatant fluid. The H2O2 is believed to result from the reaction of oxyhemoglobin with ascorbate."}
{"id": "PMID:12161", "title": "Control of phosphofructokinase from rat skeletal muscle. Effects of fructose diphosphate, AMP, ATP, and citrate.", "content": "Under conditions used previously for demonstrating glycolytic oscillations in muscle extracts (pH 6.65, 0.1 to 0.5 mM ATP), phosphofructokinase from rat skeletal muscle is strongly activated by micromolar concentrations of fructose diphosphate. The activation is dependent on the presence of AMP. Activation by fructose diphosphate and AMP, and inhibition by ATP, is primarily due to large changes in the apparent affinity of the enzyme for the substrate fructose 6-phosphate. These control properties can account for the generation of glycolytic oscillations. The enzyme was also studied under conditions approximating the metabolite contents of skeletal muscle in vivo (pH 7.0, 10mM ATP, 0.1 mM fructose 6-phosphate). Under these more inhibitory conditions, phosphofructokinase is strongly activated by low concentrations of fructose diphosphate, with half-maximal activation at about 10 muM. Citrate is a potent inhibitor at physiological concentrations, whereas AMP is a strong activator. Both AMP and citrate affect the maximum velocity and have little effect on affinity of the enzyme for fructose diphosphate.", "contents": "Control of phosphofructokinase from rat skeletal muscle. Effects of fructose diphosphate, AMP, ATP, and citrate. Under conditions used previously for demonstrating glycolytic oscillations in muscle extracts (pH 6.65, 0.1 to 0.5 mM ATP), phosphofructokinase from rat skeletal muscle is strongly activated by micromolar concentrations of fructose diphosphate. The activation is dependent on the presence of AMP. Activation by fructose diphosphate and AMP, and inhibition by ATP, is primarily due to large changes in the apparent affinity of the enzyme for the substrate fructose 6-phosphate. These control properties can account for the generation of glycolytic oscillations. The enzyme was also studied under conditions approximating the metabolite contents of skeletal muscle in vivo (pH 7.0, 10mM ATP, 0.1 mM fructose 6-phosphate). Under these more inhibitory conditions, phosphofructokinase is strongly activated by low concentrations of fructose diphosphate, with half-maximal activation at about 10 muM. Citrate is a potent inhibitor at physiological concentrations, whereas AMP is a strong activator. Both AMP and citrate affect the maximum velocity and have little effect on affinity of the enzyme for fructose diphosphate."}
{"id": "PMID:12162", "title": "Solubilized nuclear \"receptors\" for thyroid hormones. Physical characteristics and binding properties, evidence for multiple forms.", "content": "Tissues regulated by thyroid hormones contain chromatin-localized \"receptors\" that may be involved in the actions of these hormones. In this report, we describe some properties of these receptors after their solubilization from rat liver nuclei and their separation from nucleic acids and basic proteins. The nuclear extract and partially purified preparations contain a dominant class of binding sites which have a high affinity for triiodothyronine (3,5,3'-triiodo-L-thyronine, Kd approximately 1 nM) and for the biologically potent isopropyl diiodothyronine (3,5-diiodo-3'-isopropyl-L-thyronine, Kd congruent to 1 nM) and also bind thyroxine (3,5,3',5'-tetraiodo-L-thyronine, Kd approximately 5 nM) and reverse triiodothyronine (3,3',5'-triiodo-L-thyronine, Kd approximately nM). This binding activity elutes on Sephadex G-100 in an included peak which has a Stokes radius of 35 A and sediments on glycerol gradients at 3.5 S. From these data a molecular weight ratio of 50,500 and a frictional ratio of 1.4 were calculated, suggesting that the receptor is somewhat asymmetrical. There was a sharp decline in triiodothyronine binding by this component above pH 8.7 (optimum around pH 7.6) where there is marked dissociation of the 4' phenolic hydroxyl of triiodothyronine (pKalpha approximately 8.5). A similar decrease in thyroxine (pKalpha approximately 6.7) binding with pH increases in this range was not observed. Thus, ionization of the phenolic hydroxyl may influence binding. The solubilized preparations can also contain a minor specific-binding component that can be identified by binding analyses, and by G-100 or quaternary aminoethyl Sephadex chromatography. this component has a much lower affinity for triiodothyronine and isopropyl diiodothyronine than for thyroxine as compared to the major component. It probably has a pH optima around 6.0 and demonstrates and apparent tendency to aggregate. The minor component was not always identified by direct Scatchard analysis and may be generated in part from the major component as it was more commonly observed after storage or purification of the nuclear extract. Thus, at least two thyroid hormone-binding components can be present in extracts of purified rat liver nuclei; the minor component may be an altered form or subunit of the major component. The relative binding activities of triiodothyronine, isopropyl diiodothyronine, and thyroxine by the major component, similar to those in intact nuclei, parallel the biological potencies of these compounds, and suggest that the dominant binding is by biologically relevant receptors. Since ionization of the phenolic hydroxyl may influence binding, the lower activity of thyroxine relative to triiodothyronine may in part be due to the fact that at physiological pH, the phenolic hydroxyl of thyroxine is more dissociated than is that of triiodothyronine. The finding that this receptor is somewhat asymmetrical provides an indication of the shape of an intrinsic chromatin protein implicated in specific gene regulation...", "contents": "Solubilized nuclear \"receptors\" for thyroid hormones. Physical characteristics and binding properties, evidence for multiple forms. Tissues regulated by thyroid hormones contain chromatin-localized \"receptors\" that may be involved in the actions of these hormones. In this report, we describe some properties of these receptors after their solubilization from rat liver nuclei and their separation from nucleic acids and basic proteins. The nuclear extract and partially purified preparations contain a dominant class of binding sites which have a high affinity for triiodothyronine (3,5,3'-triiodo-L-thyronine, Kd approximately 1 nM) and for the biologically potent isopropyl diiodothyronine (3,5-diiodo-3'-isopropyl-L-thyronine, Kd congruent to 1 nM) and also bind thyroxine (3,5,3',5'-tetraiodo-L-thyronine, Kd approximately 5 nM) and reverse triiodothyronine (3,3',5'-triiodo-L-thyronine, Kd approximately nM). This binding activity elutes on Sephadex G-100 in an included peak which has a Stokes radius of 35 A and sediments on glycerol gradients at 3.5 S. From these data a molecular weight ratio of 50,500 and a frictional ratio of 1.4 were calculated, suggesting that the receptor is somewhat asymmetrical. There was a sharp decline in triiodothyronine binding by this component above pH 8.7 (optimum around pH 7.6) where there is marked dissociation of the 4' phenolic hydroxyl of triiodothyronine (pKalpha approximately 8.5). A similar decrease in thyroxine (pKalpha approximately 6.7) binding with pH increases in this range was not observed. Thus, ionization of the phenolic hydroxyl may influence binding. The solubilized preparations can also contain a minor specific-binding component that can be identified by binding analyses, and by G-100 or quaternary aminoethyl Sephadex chromatography. this component has a much lower affinity for triiodothyronine and isopropyl diiodothyronine than for thyroxine as compared to the major component. It probably has a pH optima around 6.0 and demonstrates and apparent tendency to aggregate. The minor component was not always identified by direct Scatchard analysis and may be generated in part from the major component as it was more commonly observed after storage or purification of the nuclear extract. Thus, at least two thyroid hormone-binding components can be present in extracts of purified rat liver nuclei; the minor component may be an altered form or subunit of the major component. The relative binding activities of triiodothyronine, isopropyl diiodothyronine, and thyroxine by the major component, similar to those in intact nuclei, parallel the biological potencies of these compounds, and suggest that the dominant binding is by biologically relevant receptors. Since ionization of the phenolic hydroxyl may influence binding, the lower activity of thyroxine relative to triiodothyronine may in part be due to the fact that at physiological pH, the phenolic hydroxyl of thyroxine is more dissociated than is that of triiodothyronine. The finding that this receptor is somewhat asymmetrical provides an indication of the shape of an intrinsic chromatin protein implicated in specific gene regulation..."}
{"id": "PMID:12163", "title": "Photoactivated cross-linking of proteins within the erythrocyte membrane core.", "content": "We describe the reactions of three lipophilic, photoactivated cross-linking reagents, 1,5-diazidonapthalene, 4,4'-diazidobiphenyl, and the reversible 4,4'-dithiobisphenylazide, with erythrocyte membranes. Cross-linking occurs only upon photoactivation. At pH 7 to 8, only spectrin components are cross-linked by these reagents. At pH 5.0 to 5.5 several additional membrane proteins including the major \"integral\" membrane proteins are also cross-linked, despite equivalent binding of the cross-linkers at neutral and acid pH. The cross-linking rates of various membrane proteins at pH 5.0 to 5.5 depend distinctly upon duration of photoactivation. Bidimensional electrophoresis of membrane proteins after cross-linking with the reversible cross-linker, 4,4'-dithiobisphenylazide, has allowed for the identification of homopolymeric products of cross-linking (e.g. dimers and tetramers of Band 3) and heterocomplexes (spectrin plus other membrane proteins). The data suggest that at reduced pH, cross-linking can proceed not only at the membrane surface but also in the membrane core.", "contents": "Photoactivated cross-linking of proteins within the erythrocyte membrane core. We describe the reactions of three lipophilic, photoactivated cross-linking reagents, 1,5-diazidonapthalene, 4,4'-diazidobiphenyl, and the reversible 4,4'-dithiobisphenylazide, with erythrocyte membranes. Cross-linking occurs only upon photoactivation. At pH 7 to 8, only spectrin components are cross-linked by these reagents. At pH 5.0 to 5.5 several additional membrane proteins including the major \"integral\" membrane proteins are also cross-linked, despite equivalent binding of the cross-linkers at neutral and acid pH. The cross-linking rates of various membrane proteins at pH 5.0 to 5.5 depend distinctly upon duration of photoactivation. Bidimensional electrophoresis of membrane proteins after cross-linking with the reversible cross-linker, 4,4'-dithiobisphenylazide, has allowed for the identification of homopolymeric products of cross-linking (e.g. dimers and tetramers of Band 3) and heterocomplexes (spectrin plus other membrane proteins). The data suggest that at reduced pH, cross-linking can proceed not only at the membrane surface but also in the membrane core."}
{"id": "PMID:12164", "title": "Evaluation of the H+/site ratio of mitochondrial electron transport from rate measurements.", "content": "The mitochondrial H+/site ratio (i.e. the number of protons ejected per pair of electrons traversing each of the energy-conserving sites of the respiratory chain) has been evaluated employing a new experimental approach. In this method the rates of oxygen uptake and H+ ejection were measured simultaneously during the initial period of respiration evoked by addition of succinate to aerobic, rotenone-inhibited, de-energized mitochondria. Either K+, in the presence of valinomycin, or Ca2+, was used as mobile cation to dissipate the membrane potential and allow quantitative H+ ejection into the medium. The H+/site ratio observed with this method in the absence of precautions to inhibit the uptake of phosphate was close to 2.0, in agreement with values obtained using the oxygen pulse technique (Mitchell, P. and Moyle, J. (1967) Biochem. J. 105, 1147-1162). However, when phosphate movements were eliminated either by inhibition of the phosphate-hydroxide antiporter with N-ethylamaleimide or by depleting the mitochondria of their endogenous phosphate content, H+/site ratios close to 4.0 were consistently observed. This ratio was independent of the concentration of succinate, of mitochondrial protein, of pH between 6 and 8, and of ionic composition of the medium, provided that sufficient K+ (plus valinomycin) or Ca2+ were present. Specific inhibitors of the hydrolysis of endogenous ATP or transport of other ions (adenine nucleotides, tricarboxylates, HCO3-, etc.) were shown not to affect the observed H+/site ratio. Furthermore, the replacement of succinate by alpha-glycerol phosphate, a substrate which is oxidized on the outer surface of the inner membrane and thus does not need to enter the matrix, gave the same H+/site ratios as did succinate. It is concluded that the H+/site ratio of mitochondrial electron transport, when phosphate movements are eliminated, may be close to 4.0.", "contents": "Evaluation of the H+/site ratio of mitochondrial electron transport from rate measurements. The mitochondrial H+/site ratio (i.e. the number of protons ejected per pair of electrons traversing each of the energy-conserving sites of the respiratory chain) has been evaluated employing a new experimental approach. In this method the rates of oxygen uptake and H+ ejection were measured simultaneously during the initial period of respiration evoked by addition of succinate to aerobic, rotenone-inhibited, de-energized mitochondria. Either K+, in the presence of valinomycin, or Ca2+, was used as mobile cation to dissipate the membrane potential and allow quantitative H+ ejection into the medium. The H+/site ratio observed with this method in the absence of precautions to inhibit the uptake of phosphate was close to 2.0, in agreement with values obtained using the oxygen pulse technique (Mitchell, P. and Moyle, J. (1967) Biochem. J. 105, 1147-1162). However, when phosphate movements were eliminated either by inhibition of the phosphate-hydroxide antiporter with N-ethylamaleimide or by depleting the mitochondria of their endogenous phosphate content, H+/site ratios close to 4.0 were consistently observed. This ratio was independent of the concentration of succinate, of mitochondrial protein, of pH between 6 and 8, and of ionic composition of the medium, provided that sufficient K+ (plus valinomycin) or Ca2+ were present. Specific inhibitors of the hydrolysis of endogenous ATP or transport of other ions (adenine nucleotides, tricarboxylates, HCO3-, etc.) were shown not to affect the observed H+/site ratio. Furthermore, the replacement of succinate by alpha-glycerol phosphate, a substrate which is oxidized on the outer surface of the inner membrane and thus does not need to enter the matrix, gave the same H+/site ratios as did succinate. It is concluded that the H+/site ratio of mitochondrial electron transport, when phosphate movements are eliminated, may be close to 4.0."}
{"id": "PMID:12165", "title": "Nuclear magnetic resonance studies of sperm whale myoglobin specifically enriched with 13C in the methionine methyl groups.", "content": "The Cepsilon methyl group of the 2 methionine residues in sperm whale myoglobin was enriched with respect to 13C. This was accomplished by treatment of the apomyoglobin at pH 4 at room temperature with a 100-fold proportion of 13CH3I to form an intermediate containing enriched S-methylmethionine. Unselective demethylation to regain the apomyoglobin structure was accomplished by treatment at pH 10.5 with 0.5 M dithioerythritol at 37 degrees for 18 h. Reagents were removed at each stage by dialysis against dilute sodium azide solution. Hemin was reincorporated to form the holoprotein in a way that avoided the presence of an excess of the small molecule. After chromatographic purification the enriched myoglobin was obtained in a yield of between 29 and 60%. The composition, absorbance spectrum, circular dichroism spectrum, isoionic point, electrophoretic behavior, and oxygen-binding behavior following reduction were all indistinguishable from those of the virgin protein. NMR measurements were made at 15.1, 25.2, and 67.9 MHz at 27-30 degrees. The two enriched loci are represented by separate resonances that appear slightly downfield of the spectral position of the corresponding resonance in free methionine. The positions of these resonances are sensitive to pH and to the ligand bound at the heme group which is approximately 17 A distant from each methionine Cepsilon. On the basis of two separate types of experiment the downfield resonance was assigned to methionine 55 and the upfield resonance to methionine 131. Part of the observed variations in chemical shift could be treated as arising from pseudocontact interactions but part was ascribed to structural changes communicated to the environment of each methionine residue as a result of changes in heme ligand, pH, or temperature. The linewidths of the methionine Cepsilon resonances are narrowed by increasing temperature according to an Arrhenius energy of activation of nearly 3 kcal. The spin-lattice relaxation times, T1, of the two methionine Cepsilon resonances at the three spectrometer frequencies were interpreted to indicate the existence of rotational motions in each side chain in addition to that about the Sdelta-Cepsilon bond. The results as a whole show that the two methionine side chains undergo continuous variations in environment, and that these variations are controlled by events at a distance within the protein structure. It is suggested that the structural lability serves the function of facilitating conformational variations and adjustments within the heme pocket.", "contents": "Nuclear magnetic resonance studies of sperm whale myoglobin specifically enriched with 13C in the methionine methyl groups. The Cepsilon methyl group of the 2 methionine residues in sperm whale myoglobin was enriched with respect to 13C. This was accomplished by treatment of the apomyoglobin at pH 4 at room temperature with a 100-fold proportion of 13CH3I to form an intermediate containing enriched S-methylmethionine. Unselective demethylation to regain the apomyoglobin structure was accomplished by treatment at pH 10.5 with 0.5 M dithioerythritol at 37 degrees for 18 h. Reagents were removed at each stage by dialysis against dilute sodium azide solution. Hemin was reincorporated to form the holoprotein in a way that avoided the presence of an excess of the small molecule. After chromatographic purification the enriched myoglobin was obtained in a yield of between 29 and 60%. The composition, absorbance spectrum, circular dichroism spectrum, isoionic point, electrophoretic behavior, and oxygen-binding behavior following reduction were all indistinguishable from those of the virgin protein. NMR measurements were made at 15.1, 25.2, and 67.9 MHz at 27-30 degrees. The two enriched loci are represented by separate resonances that appear slightly downfield of the spectral position of the corresponding resonance in free methionine. The positions of these resonances are sensitive to pH and to the ligand bound at the heme group which is approximately 17 A distant from each methionine Cepsilon. On the basis of two separate types of experiment the downfield resonance was assigned to methionine 55 and the upfield resonance to methionine 131. Part of the observed variations in chemical shift could be treated as arising from pseudocontact interactions but part was ascribed to structural changes communicated to the environment of each methionine residue as a result of changes in heme ligand, pH, or temperature. The linewidths of the methionine Cepsilon resonances are narrowed by increasing temperature according to an Arrhenius energy of activation of nearly 3 kcal. The spin-lattice relaxation times, T1, of the two methionine Cepsilon resonances at the three spectrometer frequencies were interpreted to indicate the existence of rotational motions in each side chain in addition to that about the Sdelta-Cepsilon bond. The results as a whole show that the two methionine side chains undergo continuous variations in environment, and that these variations are controlled by events at a distance within the protein structure. It is suggested that the structural lability serves the function of facilitating conformational variations and adjustments within the heme pocket."}
{"id": "PMID:12166", "title": "Investigation of microsomal oxygenases of biosynthetic processes. Stearyl-CoA desaturase of adipose tissue and liver.", "content": "Porcine and rat microsomal stearyl-CoA desaturases require reduced pyridine nucleotide and oxygen, are cyanide sensitive, and are insensitive to carbon monoxide. The Km for stearyl-CoA is somewhat larger for liver than for the adipose desaturases, but, in general, assay conditions are quite similar. Adipose tissue microsomes contain cytochromes b5 and P-450, as well as the NADH- and NADPH-specific cytochrome reductases. Compared to liver, the specific contents and activities of electron carriers are much lower in adipose tissue, and activities of 4-methyl sterol oxidase of cholesterol biosynthesis, as well as the cytochrome P-450-dependent aminopyrene demethylase and benzypyrene hydroxylase, are negligible in adipose tissue microsomes. Furthermore, unlike hepatic desaturase, administration of insulin stimulates the adipose desaturase 3-fold without affecting either the amounts or activities of microsomal oxidation-reduction proteins; the changes in desaturase activities produced either by altering dietary fat or by fasting and/or fasting followed by refeeding are, in general, both more extensive and more permanent in adipose compared to liver microsomes. The effects produced by isotopic hydrogen substitution both in stearyl-CoA and in the medium (2H2O) are similar with microsomes from both tissues. The rate-determining step of desaturase appears to be similar in both tissues. The primary isotope effect, k H/Tr, observed with [9,10-3H2]stearyl-CoA is relatively small, 2.88. Since little, if any, primary isotope effect is associated with methyl sterol oxidase, these two mixed function oxidases of biosynthetic processes also appear to share this property in common.", "contents": "Investigation of microsomal oxygenases of biosynthetic processes. Stearyl-CoA desaturase of adipose tissue and liver. Porcine and rat microsomal stearyl-CoA desaturases require reduced pyridine nucleotide and oxygen, are cyanide sensitive, and are insensitive to carbon monoxide. The Km for stearyl-CoA is somewhat larger for liver than for the adipose desaturases, but, in general, assay conditions are quite similar. Adipose tissue microsomes contain cytochromes b5 and P-450, as well as the NADH- and NADPH-specific cytochrome reductases. Compared to liver, the specific contents and activities of electron carriers are much lower in adipose tissue, and activities of 4-methyl sterol oxidase of cholesterol biosynthesis, as well as the cytochrome P-450-dependent aminopyrene demethylase and benzypyrene hydroxylase, are negligible in adipose tissue microsomes. Furthermore, unlike hepatic desaturase, administration of insulin stimulates the adipose desaturase 3-fold without affecting either the amounts or activities of microsomal oxidation-reduction proteins; the changes in desaturase activities produced either by altering dietary fat or by fasting and/or fasting followed by refeeding are, in general, both more extensive and more permanent in adipose compared to liver microsomes. The effects produced by isotopic hydrogen substitution both in stearyl-CoA and in the medium (2H2O) are similar with microsomes from both tissues. The rate-determining step of desaturase appears to be similar in both tissues. The primary isotope effect, k H/Tr, observed with [9,10-3H2]stearyl-CoA is relatively small, 2.88. Since little, if any, primary isotope effect is associated with methyl sterol oxidase, these two mixed function oxidases of biosynthetic processes also appear to share this property in common."}
{"id": "PMID:12167", "title": "Effect of organic phosphates on methemoglobin reduction by ascorbic acid.", "content": "The rate of methemoglobin reduction by ascorbic acid was accelerated in the presence of ATP,2,3-diphosphoglycerate (2,3-DPG), and inositol hexaphosphate (IHP). The acceleration was as much as three times, four times, and ten times in the presence of ATP, 2.3-DPG, and IHP at pH 7.0, respectively. The changes of the concentrations of methemoglobin and ascorbic acid during the methemoglobin reduction were determined, and the reaction was found to proceed stoichiometrically in the presence of IHP. The reduction rate of methemoglobin by ascorbic acid was compared at different concentrations of organic phosphates (ATP,2,3-DPG, and IHP) at various pH values (6.3, 7.0, 7.7). From the changes in the reduction rate under different concentrations of organic phosphates, the dissociation constants of ATP, 2,3-DPG, and IHP to methemoglobin could be determined and were estimated to be 3.3 X 10(-4) M, 2 X 10(-3) M, and 8 X 10(-6) M at pH 7.0, respectively. On the basis of these results, the acceleration mechanism of methemoglobin reduction by ascorbic acid due to the presence of organic phosphates was described. The physiological role of 2,3-DPG in human red cells was discussed in relation to the reduction of methemoglobin by ascorbic acid.", "contents": "Effect of organic phosphates on methemoglobin reduction by ascorbic acid. The rate of methemoglobin reduction by ascorbic acid was accelerated in the presence of ATP,2,3-diphosphoglycerate (2,3-DPG), and inositol hexaphosphate (IHP). The acceleration was as much as three times, four times, and ten times in the presence of ATP, 2.3-DPG, and IHP at pH 7.0, respectively. The changes of the concentrations of methemoglobin and ascorbic acid during the methemoglobin reduction were determined, and the reaction was found to proceed stoichiometrically in the presence of IHP. The reduction rate of methemoglobin by ascorbic acid was compared at different concentrations of organic phosphates (ATP,2,3-DPG, and IHP) at various pH values (6.3, 7.0, 7.7). From the changes in the reduction rate under different concentrations of organic phosphates, the dissociation constants of ATP, 2,3-DPG, and IHP to methemoglobin could be determined and were estimated to be 3.3 X 10(-4) M, 2 X 10(-3) M, and 8 X 10(-6) M at pH 7.0, respectively. On the basis of these results, the acceleration mechanism of methemoglobin reduction by ascorbic acid due to the presence of organic phosphates was described. The physiological role of 2,3-DPG in human red cells was discussed in relation to the reduction of methemoglobin by ascorbic acid."}
{"id": "PMID:12169", "title": "pH-dependent effects of Cr(NH3)2ATP on kinetics of yeast hexokinase PII. Relationship to the slow transition mechanism.", "content": "The effect of Cr(NH3)2ATP, a virtually inert, inner sphere metal-ligand complex, on the kinetics of purified yeast hexokinase PII has been studied at pH 6.5 and pH 7.5. At pH 6.5, where the normal assays exhibit a slow burst-type transient, low concentrations of Cr(NH3)2ATP were found to activate both phii, the initial velocity, and phiII, the steady state velocity. At higher concentrations, Cr(NH3)2ATP was found to be a competitive inhibitor versus MgATP for both phii and phiII. The apparent Ki values for both velocities were the same. The inhibition by Cr(NH3)2ATP at pH 6.5 was found to be a slow process with half-times similar to those found for the normal burst-type transient at this pH value. At pH 7.5, where normal assays exhibit linear progress curves, Cr(NH3)2ATP behaved similarly to that observed before at pH 7 (Danenberg, D. D., and Cleland, W. W. (1975) Biochemistry 14, 28-39), i.e. it was a competitive inhibitor versus MgATP and it caused a slowing of the reaction rate over the first several minutes. The apparent Ki for the initial velocity was 8-fold higher than the apparent Ki for the steady state velocity, suggesting tighter binding of Cr(NH3)2ATP with time. Preincubation experiments indicated that the normal pH 6.5 burst-type transient could be eliminated by appropriate preincubation with Cr(NH3)2ATP and a sugar. In agreement with Danenberg and Cleland (1975), similar preincubations have been shown to produce linear assays at pH 7.5 in the presence of Cr(NH3)2ATP. Similar results were seen with MgITP as the nucleotide substrate, where a burst-type transient is not seen at either pH value under normal assay conditions. At pH 7.5, a slow decrease in the reaction rate is seen over the first several minutes in the presence of Cr(NH3)2ATP. The apparent Ki for phii was 7-fold higher than the apparent Ki value for phiII, again suggesting a tighter binding of Cr(NH3)2ATP with time. A similar observation was made at pH 6.5, but the Ki values for phii and phiII were the same, suggesting no tightening of the binding of Cr(NH3)2ATP with time at this pH value. These results suggested that both slow processes reflect the same basic molecular change, but the consequences are different at the two pH values, presumably because of the difference in the charge of the enzyme. The Cr(NH3)2ATP kinetics at pH 6.5 have been interpreted in terms of a modification of the slow transition mechanism for hexokinase (Shill, J. P., and Neet, K. E. (1975) J. Biol. Chem. 250, 2259-2268). It is postulated that glucose and Cr(NH3)2ATP induce the same slow conformational change at pH 6.5 as that induced by glucose and MgATP, which gives rise to the normal burst-type transient. This suggests that Cr(NH3)2ATP may be a useful tool for physical studies to determine the cause of the slow transition of yeast hexokinase. Activation by low concentrations of Cr(NH3)2ATP was interpreted as binding of the nucleotide to an activator site on the enzyme, causing a shift in the distribution of enzyme towards the more active form.", "contents": "pH-dependent effects of Cr(NH3)2ATP on kinetics of yeast hexokinase PII. Relationship to the slow transition mechanism. The effect of Cr(NH3)2ATP, a virtually inert, inner sphere metal-ligand complex, on the kinetics of purified yeast hexokinase PII has been studied at pH 6.5 and pH 7.5. At pH 6.5, where the normal assays exhibit a slow burst-type transient, low concentrations of Cr(NH3)2ATP were found to activate both phii, the initial velocity, and phiII, the steady state velocity. At higher concentrations, Cr(NH3)2ATP was found to be a competitive inhibitor versus MgATP for both phii and phiII. The apparent Ki values for both velocities were the same. The inhibition by Cr(NH3)2ATP at pH 6.5 was found to be a slow process with half-times similar to those found for the normal burst-type transient at this pH value. At pH 7.5, where normal assays exhibit linear progress curves, Cr(NH3)2ATP behaved similarly to that observed before at pH 7 (Danenberg, D. D., and Cleland, W. W. (1975) Biochemistry 14, 28-39), i.e. it was a competitive inhibitor versus MgATP and it caused a slowing of the reaction rate over the first several minutes. The apparent Ki for the initial velocity was 8-fold higher than the apparent Ki for the steady state velocity, suggesting tighter binding of Cr(NH3)2ATP with time. Preincubation experiments indicated that the normal pH 6.5 burst-type transient could be eliminated by appropriate preincubation with Cr(NH3)2ATP and a sugar. In agreement with Danenberg and Cleland (1975), similar preincubations have been shown to produce linear assays at pH 7.5 in the presence of Cr(NH3)2ATP. Similar results were seen with MgITP as the nucleotide substrate, where a burst-type transient is not seen at either pH value under normal assay conditions. At pH 7.5, a slow decrease in the reaction rate is seen over the first several minutes in the presence of Cr(NH3)2ATP. The apparent Ki for phii was 7-fold higher than the apparent Ki value for phiII, again suggesting a tighter binding of Cr(NH3)2ATP with time. A similar observation was made at pH 6.5, but the Ki values for phii and phiII were the same, suggesting no tightening of the binding of Cr(NH3)2ATP with time at this pH value. These results suggested that both slow processes reflect the same basic molecular change, but the consequences are different at the two pH values, presumably because of the difference in the charge of the enzyme. The Cr(NH3)2ATP kinetics at pH 6.5 have been interpreted in terms of a modification of the slow transition mechanism for hexokinase (Shill, J. P., and Neet, K. E. (1975) J. Biol. Chem. 250, 2259-2268). It is postulated that glucose and Cr(NH3)2ATP induce the same slow conformational change at pH 6.5 as that induced by glucose and MgATP, which gives rise to the normal burst-type transient. This suggests that Cr(NH3)2ATP may be a useful tool for physical studies to determine the cause of the slow transition of yeast hexokinase. Activation by low concentrations of Cr(NH3)2ATP was interpreted as binding of the nucleotide to an activator site on the enzyme, causing a shift in the distribution of enzyme towards the more active form."}
{"id": "PMID:12170", "title": "Catalytic mechanisms of glutamine synthetase enzymes. Studies with analogs of possible intermediates and transition states.", "content": "Glutamine synthetase enzymes isolated from pea seeds and from Escherichia coli are observed to behave differently in experiments designed to probe reaction mechanism. Although both enzymes were found to bind and release substrates in random order mechanisms (Wedler, F.C. (1974) J. Biol. Chem, 247, 5080-5087), isotopic exchanges with partial reaction systems indicative of a gamma-glutamylphosphate intermediate are catalyzed only by the pea seed enzyme. The E. coli system fails to catalyze any exchanges at appreciable rates unless all substrates are present. This negative result implies either an absolute conformational requirement for bound substrates or that the putative complex (E-Glu-P-MgADP) is exceedingly tight. To test the latter, a nonreactive structural analog of gamma-glutamyl-phosphate, namely 3-(phosphonoacetylamido)-L-alanine (PA2LA), has been synthesized. With the E. coli enzyme PA2LA was found to bind no more tightly than L-glutamate and is strictly competitive versus L-glutamate (Ki = 3 mM). Thus, failure to catalyze partial exchange reactions indicative of gamma-Glu-P is probably not attributable to tight complex formation. The binding of PA2LA with the pea seed enzyme apparently involves a two-step process: a rapid, reversible step in which PA2LA binds 10-fold more tightly than L-glutamate, followed by a slow (but reversible) process involving very tight PA2LA binding, apparently with enzyme isomerization promoted by nucleotide. The specificity of the two enzymes toward L-methionine-SR-sulfoximine, Met(O)(NH), was also different...", "contents": "Catalytic mechanisms of glutamine synthetase enzymes. Studies with analogs of possible intermediates and transition states. Glutamine synthetase enzymes isolated from pea seeds and from Escherichia coli are observed to behave differently in experiments designed to probe reaction mechanism. Although both enzymes were found to bind and release substrates in random order mechanisms (Wedler, F.C. (1974) J. Biol. Chem, 247, 5080-5087), isotopic exchanges with partial reaction systems indicative of a gamma-glutamylphosphate intermediate are catalyzed only by the pea seed enzyme. The E. coli system fails to catalyze any exchanges at appreciable rates unless all substrates are present. This negative result implies either an absolute conformational requirement for bound substrates or that the putative complex (E-Glu-P-MgADP) is exceedingly tight. To test the latter, a nonreactive structural analog of gamma-glutamyl-phosphate, namely 3-(phosphonoacetylamido)-L-alanine (PA2LA), has been synthesized. With the E. coli enzyme PA2LA was found to bind no more tightly than L-glutamate and is strictly competitive versus L-glutamate (Ki = 3 mM). Thus, failure to catalyze partial exchange reactions indicative of gamma-Glu-P is probably not attributable to tight complex formation. The binding of PA2LA with the pea seed enzyme apparently involves a two-step process: a rapid, reversible step in which PA2LA binds 10-fold more tightly than L-glutamate, followed by a slow (but reversible) process involving very tight PA2LA binding, apparently with enzyme isomerization promoted by nucleotide. The specificity of the two enzymes toward L-methionine-SR-sulfoximine, Met(O)(NH), was also different..."}
{"id": "PMID:12171", "title": "Adrenodoxin reductase-adrenodexin complex.", "content": "Adrenodoxin reductase and adrenodoxin have been shown (Chu, J.-W., and Kimura, T. (1973) J. Biol. Chem. 248, 5183-5187) to form a low dissociation constant, 1:1 complex when both proteins are in the oxidized form. We have found that when adrenodoxin: adrenodoxin reductase ratios are varied by increasing the adrenodoxin concentration, with adrenodoxin reductase held constant, an increasing rate of cytochrome c reduction, with NADPH as reductant, is seen up to a ratio of 1:1, indicating that cytochrome c reduction occurs via the protein-protein complex. Spectra observed during titration of this protein-protein complex with NADH were resolved into components by the linear programming method, using a computer program written in Fortran IV. Analysis of the data has shown that the flavoprotein is reduced prior to the iron sulfur protein, and that the midpoint oxidation-reduction potentials (pH 7.5) of the two proteins are -295 and -331 mV, respectively, when both are present in the complex. Complex formation does not alter the potential of adrenodoxin reductase, but changes that of adrenodoxin by -40 mV. Equilibrium constants derived from potential measurements show that the strength of the protein-protein interaction in the complex is unaltered by reduction of adrenodoxin reductase, but is decreased by about 1 kcal due to reduction of adrenodoxin. The low dissociation constants for both oxidized reduced forms of the adrenodoxin reductase-adrenodoxin complex indicate that the complex must remain associated throughout its catalytic cycle. Titration of the adrenodoxin reductase-adrenodoxin complex with the physiologic reductant, NADPH, was followed by EPR and visible spectra, and yielded an order of reduction of the components identical with that seen when NADH was used as reductant. Reduction of the protein-protein complex with NADPH yielded a ternary complex between NADP+, flavoprotein, and iron sulfur protein, with the two electrons located in a \"charge transfer\" complex between flavoprotein and pyridine nucleotide.", "contents": "Adrenodoxin reductase-adrenodexin complex. Adrenodoxin reductase and adrenodoxin have been shown (Chu, J.-W., and Kimura, T. (1973) J. Biol. Chem. 248, 5183-5187) to form a low dissociation constant, 1:1 complex when both proteins are in the oxidized form. We have found that when adrenodoxin: adrenodoxin reductase ratios are varied by increasing the adrenodoxin concentration, with adrenodoxin reductase held constant, an increasing rate of cytochrome c reduction, with NADPH as reductant, is seen up to a ratio of 1:1, indicating that cytochrome c reduction occurs via the protein-protein complex. Spectra observed during titration of this protein-protein complex with NADH were resolved into components by the linear programming method, using a computer program written in Fortran IV. Analysis of the data has shown that the flavoprotein is reduced prior to the iron sulfur protein, and that the midpoint oxidation-reduction potentials (pH 7.5) of the two proteins are -295 and -331 mV, respectively, when both are present in the complex. Complex formation does not alter the potential of adrenodoxin reductase, but changes that of adrenodoxin by -40 mV. Equilibrium constants derived from potential measurements show that the strength of the protein-protein interaction in the complex is unaltered by reduction of adrenodoxin reductase, but is decreased by about 1 kcal due to reduction of adrenodoxin. The low dissociation constants for both oxidized reduced forms of the adrenodoxin reductase-adrenodoxin complex indicate that the complex must remain associated throughout its catalytic cycle. Titration of the adrenodoxin reductase-adrenodoxin complex with the physiologic reductant, NADPH, was followed by EPR and visible spectra, and yielded an order of reduction of the components identical with that seen when NADH was used as reductant. Reduction of the protein-protein complex with NADPH yielded a ternary complex between NADP+, flavoprotein, and iron sulfur protein, with the two electrons located in a \"charge transfer\" complex between flavoprotein and pyridine nucleotide."}
{"id": "PMID:12172", "title": "Hemoglobin providence. Functional consequences of two alterations of the 2,3-diphosphoglycerate binding site at position beta 82.", "content": "Position beta 82 in human hemoglobin (Hb) is normally occupied by lysine, a positively charged residue that is involved in the binding of anionic cofactors. This residue is substituted by a neutral residue in Hb Providence Asn and by a negatively charged residue in Hb Providence Asp. Hb Providence Asp shows more differences from Hb A than does Hb Providence Asn in studies of the kinetics and equilibria of ligand binding. For both forms, homotropic (cooperative) interactions are normal with n values of 2.5 to 2.7, while heterotropic (pH and anion) interactions are reduced greatly. The reduction in anion sensitivity is attributed to the absence of a positive residue at position beta 82. Reduction in pH sensitivity may be due to a ligand-linked change in the pK of a neighboring residue, beta 143 histidine, which normally is not a Bohr group. This change in pK would act in opposition to the normal Bohr effect. Reduction in the net positive charge of the central cavity has a further consequence. Relative to Hb A, both Hb Providence Asn and Hb Providence Asp show decreased oxygen affinities at neutral pH in the absence of cofactors. This suggests that in Hb A the binding of anionic cofactors directly influences the oxygen affinity by neutralizing the charged groups of the diphosphoglycerate binding site and thus stabilizing the low affinity (T) conformation. From pH 6 to 9 in the presence of 1 M NaCl, where all the charged groups may be masked, the oxygen-binding properties of Hb A and the Hb Providence mutants are identical. Moreover, subunit dissociation of the liganded Hb Providence mutants appears to be increased, as is known to occur for Hb A in the presence of high salt. The results obtained with Hb Providence Asn and Hb Providence Asp illustrate how single amino acid substitutions can modify hemoglobins' pH and anion interactions without altering cooperative interactions between subunits. The alteration in cofactor effects observed with these mutants also illustrates differences between the allosteric effects induced by organic and inorganic anions.", "contents": "Hemoglobin providence. Functional consequences of two alterations of the 2,3-diphosphoglycerate binding site at position beta 82. Position beta 82 in human hemoglobin (Hb) is normally occupied by lysine, a positively charged residue that is involved in the binding of anionic cofactors. This residue is substituted by a neutral residue in Hb Providence Asn and by a negatively charged residue in Hb Providence Asp. Hb Providence Asp shows more differences from Hb A than does Hb Providence Asn in studies of the kinetics and equilibria of ligand binding. For both forms, homotropic (cooperative) interactions are normal with n values of 2.5 to 2.7, while heterotropic (pH and anion) interactions are reduced greatly. The reduction in anion sensitivity is attributed to the absence of a positive residue at position beta 82. Reduction in pH sensitivity may be due to a ligand-linked change in the pK of a neighboring residue, beta 143 histidine, which normally is not a Bohr group. This change in pK would act in opposition to the normal Bohr effect. Reduction in the net positive charge of the central cavity has a further consequence. Relative to Hb A, both Hb Providence Asn and Hb Providence Asp show decreased oxygen affinities at neutral pH in the absence of cofactors. This suggests that in Hb A the binding of anionic cofactors directly influences the oxygen affinity by neutralizing the charged groups of the diphosphoglycerate binding site and thus stabilizing the low affinity (T) conformation. From pH 6 to 9 in the presence of 1 M NaCl, where all the charged groups may be masked, the oxygen-binding properties of Hb A and the Hb Providence mutants are identical. Moreover, subunit dissociation of the liganded Hb Providence mutants appears to be increased, as is known to occur for Hb A in the presence of high salt. The results obtained with Hb Providence Asn and Hb Providence Asp illustrate how single amino acid substitutions can modify hemoglobins' pH and anion interactions without altering cooperative interactions between subunits. The alteration in cofactor effects observed with these mutants also illustrates differences between the allosteric effects induced by organic and inorganic anions."}
{"id": "PMID:12173", "title": "Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography.", "content": "The endopeptidase, post-proline cleaving enzyme, has been purified 10,500-fold in an overall yield of 18% from lamb kidney. The enzyme possesses a specific activity of 45 mumol/mg/min as tested with the substrate Z-Gly-Pro-Leu-Gly (Km = 6.0 X 10(-5)), has a molecular weight of 115,000, is comprised of two subunits with a molecular weight of 57,000, and exhibits maximal activity at pH 7.5 to 8.0. With the exception of the -Pro-Pro linkage, the -Pro-X-peptide bond (X equals L- and D-amino acid residues) located internally in the peptide sequence can be hydrolyzed (cleavage occurs faster when X = lipophilic side chain as compared to X = acidic side chain). The appropriate -Pro-X- bonds in zinc-free porcine insulin, oxytocin, arginine vasopressin, angiotensin II, bradykinin-potentiating factor were cleaved. Human gastrin, adrenocorticotropic hormone, denatured guinea pig skin collagen, and ascaris cuticle collagen were not degraded. Dipeptides with the structure Z-Pro-LD-X competitively inhibit post-proline cleaving enzyme.", "contents": "Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography. The endopeptidase, post-proline cleaving enzyme, has been purified 10,500-fold in an overall yield of 18% from lamb kidney. The enzyme possesses a specific activity of 45 mumol/mg/min as tested with the substrate Z-Gly-Pro-Leu-Gly (Km = 6.0 X 10(-5)), has a molecular weight of 115,000, is comprised of two subunits with a molecular weight of 57,000, and exhibits maximal activity at pH 7.5 to 8.0. With the exception of the -Pro-Pro linkage, the -Pro-X-peptide bond (X equals L- and D-amino acid residues) located internally in the peptide sequence can be hydrolyzed (cleavage occurs faster when X = lipophilic side chain as compared to X = acidic side chain). The appropriate -Pro-X- bonds in zinc-free porcine insulin, oxytocin, arginine vasopressin, angiotensin II, bradykinin-potentiating factor were cleaved. Human gastrin, adrenocorticotropic hormone, denatured guinea pig skin collagen, and ascaris cuticle collagen were not degraded. Dipeptides with the structure Z-Pro-LD-X competitively inhibit post-proline cleaving enzyme."}
{"id": "PMID:12174", "title": "A new endoribonuclease from Escherichia coli. Ribonuclease N.", "content": "A new ribonuclease called RNase N was isolated from Escherichia coli. It is a nonspecific endoribonuclease that can cleave rRNA, poly(U), and poly(C) to small oligonucleotides and 5'-mononucleotides. It requires monovalent cations and is inhibited by divalent cations. It is suggested that this enzyme plays a role in the decay of rRNA,under various starvation conditions and perhaps in the decay of mRNA.", "contents": "A new endoribonuclease from Escherichia coli. Ribonuclease N. A new ribonuclease called RNase N was isolated from Escherichia coli. It is a nonspecific endoribonuclease that can cleave rRNA, poly(U), and poly(C) to small oligonucleotides and 5'-mononucleotides. It requires monovalent cations and is inhibited by divalent cations. It is suggested that this enzyme plays a role in the decay of rRNA,under various starvation conditions and perhaps in the decay of mRNA."}
{"id": "PMID:12175", "title": "A nonelectrogenic H+ pump in plasma membranes of hog stomach.", "content": "Differential and density gradient centrifugation were used to prepare a vesicular membrane fraction from hog gastric mucosa enriched 17-fold with respect to cation-activated ATPase and 5'-AMPase. Fractionation of the gradient material by free flow electrophoresis resulted in a fraction 35-fold enriched in cation-activated ATPase and essentially free of 5'-AMPase and Mg2+ATPase. The addition of ATP to either fraction resulted in H+ uptake and Rb+ efflux. The ionophoric and osmotic sensitivity showed that these ion movements were due to transport rather than binding. The cation selectivity sequences, substrate specificities and action of inhibitors indicated that the transport was a function of K+ATPase activity. The characteristics of the ATP-dependent enhancement of SCN- uptake and 8-anilinonapthalene-1-sulfonate fluorescence in the presence of valinomycin and the action of ionophores and lipid-permeable ions suggested that the energy dependent K+:H+ exchange was effectively nonelectrogenic. Thus these vesicles contain a nonelectrogenic (H+ + K+)-ATPase, hence acid secretion by the stomach is probably due to an ATP-dependent H+ + K+ exchange.", "contents": "A nonelectrogenic H+ pump in plasma membranes of hog stomach. Differential and density gradient centrifugation were used to prepare a vesicular membrane fraction from hog gastric mucosa enriched 17-fold with respect to cation-activated ATPase and 5'-AMPase. Fractionation of the gradient material by free flow electrophoresis resulted in a fraction 35-fold enriched in cation-activated ATPase and essentially free of 5'-AMPase and Mg2+ATPase. The addition of ATP to either fraction resulted in H+ uptake and Rb+ efflux. The ionophoric and osmotic sensitivity showed that these ion movements were due to transport rather than binding. The cation selectivity sequences, substrate specificities and action of inhibitors indicated that the transport was a function of K+ATPase activity. The characteristics of the ATP-dependent enhancement of SCN- uptake and 8-anilinonapthalene-1-sulfonate fluorescence in the presence of valinomycin and the action of ionophores and lipid-permeable ions suggested that the energy dependent K+:H+ exchange was effectively nonelectrogenic. Thus these vesicles contain a nonelectrogenic (H+ + K+)-ATPase, hence acid secretion by the stomach is probably due to an ATP-dependent H+ + K+ exchange."}
{"id": "PMID:12177", "title": "Appearance of magnesium guanylate cyclase activity in rat liver with sodium azide activation.", "content": "Native soluble and particulate guanylate cyclase from several rat tissues preferred Mn2+ to Mg2+ as the sole cation cofactor. Wtih 4mM cation, activities with Mg2+ were less than 25% of the activities with Mn2+. The 1 mM NaN3 markedly increased the activity of soluble and particulate preparations from rat liver. Wtih NaN3 activation guanylate cyclase activities wite similar with Mn2+ and Mg2+. Co2+ was partially effective as a cofactor in the presence of NaN3, while Ca2+ was a poor cation with or without NaN3. Activities with Ba, Cu2+, or Zn2+ were not detectable without or with 1 mM NaN3. With soluble liver enzyme both manganese and magnesium activities were dependent upon excess Mn2+ or Mg2+ at a fixed MnGTP or MgGTP concentration of 0.4 mm; apparent Km values for excess Mn2+ and Mg2+ were 0.3 and 0.24 mM, respectively. After NaN3 activation, the activity was less dependent upon free Mn2+ and retained its dependence for free Mg2+, at 0.4 mM MgGTP the apparent Km for excess Mg2+ was 0.3 mM. The activity of soluble liver guanylate cyclase assayed with Mn2+ or Mg2+ was increased with Ca2+. After NaN3 activiation, Ca2+ had no effect or was somewhat inhibitory with either Mn2+. After NaN activation, Ca2+ had no effect or was somewhat inhibitory with either Mn2+ or Mg2+. The stimulatory effect of NaN2 on Mn2+-and Mg2+-dependent guanylate cyclase activity from liver or cerebral cortex supernatant fractions required the presence of the sodium azide-activator factor. With partially purified soluble liver guanylate cyclase and azide-activator factor, the concentration (1 mjM) of NaN3 that gave half-maximal activation with Mn2+ or Mg2+ was imilar. Thus, under some conditions guanylate cyclase can effectively use Mg2+ as a sole cation cofactor.", "contents": "Appearance of magnesium guanylate cyclase activity in rat liver with sodium azide activation. Native soluble and particulate guanylate cyclase from several rat tissues preferred Mn2+ to Mg2+ as the sole cation cofactor. Wtih 4mM cation, activities with Mg2+ were less than 25% of the activities with Mn2+. The 1 mM NaN3 markedly increased the activity of soluble and particulate preparations from rat liver. Wtih NaN3 activation guanylate cyclase activities wite similar with Mn2+ and Mg2+. Co2+ was partially effective as a cofactor in the presence of NaN3, while Ca2+ was a poor cation with or without NaN3. Activities with Ba, Cu2+, or Zn2+ were not detectable without or with 1 mM NaN3. With soluble liver enzyme both manganese and magnesium activities were dependent upon excess Mn2+ or Mg2+ at a fixed MnGTP or MgGTP concentration of 0.4 mm; apparent Km values for excess Mn2+ and Mg2+ were 0.3 and 0.24 mM, respectively. After NaN3 activation, the activity was less dependent upon free Mn2+ and retained its dependence for free Mg2+, at 0.4 mM MgGTP the apparent Km for excess Mg2+ was 0.3 mM. The activity of soluble liver guanylate cyclase assayed with Mn2+ or Mg2+ was increased with Ca2+. After NaN3 activiation, Ca2+ had no effect or was somewhat inhibitory with either Mn2+. After NaN activation, Ca2+ had no effect or was somewhat inhibitory with either Mn2+ or Mg2+. The stimulatory effect of NaN2 on Mn2+-and Mg2+-dependent guanylate cyclase activity from liver or cerebral cortex supernatant fractions required the presence of the sodium azide-activator factor. With partially purified soluble liver guanylate cyclase and azide-activator factor, the concentration (1 mjM) of NaN3 that gave half-maximal activation with Mn2+ or Mg2+ was imilar. Thus, under some conditions guanylate cyclase can effectively use Mg2+ as a sole cation cofactor."}
{"id": "PMID:12178", "title": "Synthesis of bound adenosine triphosphate from bound adenosine diphosphate by the purified coupling factor 1 of chloroplasts. Evidence for direct involvement of the coupling factor in this \"adenylate kinase-like\" reaction.", "content": "Electrophoretically homogeneous coupling factor 1 from spinach chloroplasts binds ADP and converts the bound ADP to bound ATP and AMP. That this transphosphorylation of enzyme-bound ADP is catalyzed by the coupling factor itself, and not be a conventional adenylate kinase which might possibly contaminate preparations of the coupling factor, is supported by the following evidence. 1. The procedure for isolatio of the coupling factor is designed to separate this large (approximately 13 S) enzyme from the smaller (4.2 S) conventional adenylate kinase of spinach chloroplasts. The conventional adenylate kinase cannot be detected in purified preparations of the coupling factor by biochemical assay or by polyacrylamide gel electrophoresis. 2. The activity of spinach adenylate kinase is completely dependent upon magnesium ions. However, the production of bound ATP and AMP from bound ADP by the coupling factor can be assayed in the total absence of added magnesium ions or even in the presence of added EDTA. 3. Comparative studies with inhibitors show that the coupling factor can produce bound ATP from ADP under conditions where the activity of adenylate kinase is strongly inhibited. Conversely, the coupling factor is prevented from synthesizing bound ATP from ADP under other conditions where the conventional adenylate kinase has high levels of activity. 4. AMP, when added in solution to the coupling factor, does not bind to this enzyme, even in the presence of APT. Thus, it is unlikely that the appearance of AMP bound to the coupling factor after its incubation with ADP is due to the production of free AMP by contaminating adenylate kinase. These results demonstrate that the isolated, homogeneous coupling factor from spinach chloroplasts has the intrinsic capacity to perform a phosphoryl group transfer between two bound ADP molecules and thus to synthesize ATP. This reaction may have an important role in the photosynthetic production of ATP by the chloroplast, as is discussed in this communication.", "contents": "Synthesis of bound adenosine triphosphate from bound adenosine diphosphate by the purified coupling factor 1 of chloroplasts. Evidence for direct involvement of the coupling factor in this \"adenylate kinase-like\" reaction. Electrophoretically homogeneous coupling factor 1 from spinach chloroplasts binds ADP and converts the bound ADP to bound ATP and AMP. That this transphosphorylation of enzyme-bound ADP is catalyzed by the coupling factor itself, and not be a conventional adenylate kinase which might possibly contaminate preparations of the coupling factor, is supported by the following evidence. 1. The procedure for isolatio of the coupling factor is designed to separate this large (approximately 13 S) enzyme from the smaller (4.2 S) conventional adenylate kinase of spinach chloroplasts. The conventional adenylate kinase cannot be detected in purified preparations of the coupling factor by biochemical assay or by polyacrylamide gel electrophoresis. 2. The activity of spinach adenylate kinase is completely dependent upon magnesium ions. However, the production of bound ATP and AMP from bound ADP by the coupling factor can be assayed in the total absence of added magnesium ions or even in the presence of added EDTA. 3. Comparative studies with inhibitors show that the coupling factor can produce bound ATP from ADP under conditions where the activity of adenylate kinase is strongly inhibited. Conversely, the coupling factor is prevented from synthesizing bound ATP from ADP under other conditions where the conventional adenylate kinase has high levels of activity. 4. AMP, when added in solution to the coupling factor, does not bind to this enzyme, even in the presence of APT. Thus, it is unlikely that the appearance of AMP bound to the coupling factor after its incubation with ADP is due to the production of free AMP by contaminating adenylate kinase. These results demonstrate that the isolated, homogeneous coupling factor from spinach chloroplasts has the intrinsic capacity to perform a phosphoryl group transfer between two bound ADP molecules and thus to synthesize ATP. This reaction may have an important role in the photosynthetic production of ATP by the chloroplast, as is discussed in this communication."}
{"id": "PMID:12179", "title": "Purification and properties of squid mantle adenylate kinase. Role of NADH in control of the enzyme.", "content": "Adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) from the mantle muscle of the squid, Loligo pealeii, was purified over 170-fold to homogeneity as judged by polyacrylamide and starch gel electrophoresis. The tissue contains a single isozyme of adenylate kinase, the enzyme from cytoplasmic and mitochondrial compartments (90 and 10% of total activity, respectively) being identical in physical and kinetic properties. Molecular weight was found to be 27,000 +/- 400. The enzyme shows a pH optimum of 8.2 in the forward (APD utilizing) and 7.4 in the reverse direction. Michaelis constants for ADP, ATP, and AMP are 0.70, 0.13, and 0.15 mM, respectively, with optimal Mg2+:adenylate ratios being 1:2 for ADP and 1:1 for ATP. A comparison of mass action ratios with the equilibrium constant indicated that squid adenylate kinase is held out of equilibrium in resting, but not active, muscle. A search for metabolic modulators of adenylate kinase revealed that NADH (Ki of 0.1 mM) was the only modulator which exerted a significant effect within its in vivo concentration range. The data presented indicate that NADH inhibition is the factor maintaining adenylate kinase in a nonequilibrium state in resting muscle and that release of this inhibition can serve to integrate adenylate kinase into the known scheme of intermediary metabolism in this tissue. A sharp drop in NADH levels at the onset on muscular work co-ordinates that activation of aerobic metabolism in this tissue and allows adenylate kinase to return to equilibrium function. At equilibrium, the enzyme can function to ampligy the concentration of AMP, a potent activator and deinhibitor of key glycolytic and Krebs cycle enzymes. The effect of modulators of adenylate kinase in preventing denaturation by heat or proteolysis revealed that NADH and substrates induced conformational changes in the enzyme which rendered it less susceptible to denaturation. The conformation state induced by NADH differed from that induced by substrate.", "contents": "Purification and properties of squid mantle adenylate kinase. Role of NADH in control of the enzyme. Adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) from the mantle muscle of the squid, Loligo pealeii, was purified over 170-fold to homogeneity as judged by polyacrylamide and starch gel electrophoresis. The tissue contains a single isozyme of adenylate kinase, the enzyme from cytoplasmic and mitochondrial compartments (90 and 10% of total activity, respectively) being identical in physical and kinetic properties. Molecular weight was found to be 27,000 +/- 400. The enzyme shows a pH optimum of 8.2 in the forward (APD utilizing) and 7.4 in the reverse direction. Michaelis constants for ADP, ATP, and AMP are 0.70, 0.13, and 0.15 mM, respectively, with optimal Mg2+:adenylate ratios being 1:2 for ADP and 1:1 for ATP. A comparison of mass action ratios with the equilibrium constant indicated that squid adenylate kinase is held out of equilibrium in resting, but not active, muscle. A search for metabolic modulators of adenylate kinase revealed that NADH (Ki of 0.1 mM) was the only modulator which exerted a significant effect within its in vivo concentration range. The data presented indicate that NADH inhibition is the factor maintaining adenylate kinase in a nonequilibrium state in resting muscle and that release of this inhibition can serve to integrate adenylate kinase into the known scheme of intermediary metabolism in this tissue. A sharp drop in NADH levels at the onset on muscular work co-ordinates that activation of aerobic metabolism in this tissue and allows adenylate kinase to return to equilibrium function. At equilibrium, the enzyme can function to ampligy the concentration of AMP, a potent activator and deinhibitor of key glycolytic and Krebs cycle enzymes. The effect of modulators of adenylate kinase in preventing denaturation by heat or proteolysis revealed that NADH and substrates induced conformational changes in the enzyme which rendered it less susceptible to denaturation. The conformation state induced by NADH differed from that induced by substrate."}
{"id": "PMID:12180", "title": "Latency of inosine-5'-diphosphatase in microsomes isolated from rat liver.", "content": "The latency of inosine-5'-diphosphatase has been studied in microsomes isolated from rat liver. The appearance of latent activity was the result of an increase in the Vmax of the enzyme. This was observed when assays were carried out in the presence of sodium deoxycholate, after microsomes were treated wtih phospholipase C, or at pH 10.3 and after microsomes were subjected to nitrogen cavitation. The apparent Km of inosine-5'-diphosphatase for IDP was unchanged when microsomes were treated with phospholipase C or at pH 10.3 after both these treatments approximately 85% of the enzyme remained bound to the membrane. In contrast, when microsomes were treated with phospholipase C or at pH 10.3 after both these treatments approximately 85% of the enzyme remained bound to the membrane. In contrast, when microsomes were treated with sodium deoxycholate or subjected to nitrogen cavitation, approximately 75% of the inosine-5'-diphosphatase activity was released from the membrane, and the apparent Km of the enzyme for IDP increased 4- and 2-fold, respectively. Microsomal cisternae were loaded with lead phosphate by incubation with glucose-6-P and Pb2+, and the release of this lead phosphate following the addition of EDTA to the medium was determined to estimate the permeability of the microsomal membrane. When microsomes were treated with sodium deoxycholate, phospholipase C, or at alkaline pH, the microsomal membrane became almost completely permeable to EDTA under conditions where there was little or no increase in the activity of inosine-5'-diphosphatase. Microsomes were treated at pH 10.3 and then adjusted slowly to pH 7.5. The activity of inosine-5'-diphosphatase decreased to the same activity observed in untreated preparations. The results seem of exclude the possibility that latent inosine-5'-diphosphatase activity is the result of an increased permeability of the membrane to IDP. They are, however, consistent with the presence of a noncompetitive inhibitor of the enzyme in the microsomal membrane.", "contents": "Latency of inosine-5'-diphosphatase in microsomes isolated from rat liver. The latency of inosine-5'-diphosphatase has been studied in microsomes isolated from rat liver. The appearance of latent activity was the result of an increase in the Vmax of the enzyme. This was observed when assays were carried out in the presence of sodium deoxycholate, after microsomes were treated wtih phospholipase C, or at pH 10.3 and after microsomes were subjected to nitrogen cavitation. The apparent Km of inosine-5'-diphosphatase for IDP was unchanged when microsomes were treated with phospholipase C or at pH 10.3 after both these treatments approximately 85% of the enzyme remained bound to the membrane. In contrast, when microsomes were treated with phospholipase C or at pH 10.3 after both these treatments approximately 85% of the enzyme remained bound to the membrane. In contrast, when microsomes were treated with sodium deoxycholate or subjected to nitrogen cavitation, approximately 75% of the inosine-5'-diphosphatase activity was released from the membrane, and the apparent Km of the enzyme for IDP increased 4- and 2-fold, respectively. Microsomal cisternae were loaded with lead phosphate by incubation with glucose-6-P and Pb2+, and the release of this lead phosphate following the addition of EDTA to the medium was determined to estimate the permeability of the microsomal membrane. When microsomes were treated with sodium deoxycholate, phospholipase C, or at alkaline pH, the microsomal membrane became almost completely permeable to EDTA under conditions where there was little or no increase in the activity of inosine-5'-diphosphatase. Microsomes were treated at pH 10.3 and then adjusted slowly to pH 7.5. The activity of inosine-5'-diphosphatase decreased to the same activity observed in untreated preparations. The results seem of exclude the possibility that latent inosine-5'-diphosphatase activity is the result of an increased permeability of the membrane to IDP. They are, however, consistent with the presence of a noncompetitive inhibitor of the enzyme in the microsomal membrane."}
{"id": "PMID:12181", "title": "Aggregation of deoxyhemoglobin subunits.", "content": "The formation of deoxyhemoglobin was examined by measuring the heme spectral change that accompanies the aggregation of isolated alpha and beta chains. At low hemeconcentrations (less than 10(-5) M), tetramer formation can be described by two consecutive, second order reactions representing the aggregation of monomers followed by the association of alphabeta dimers. At neutral pH, the rates of monomer and dimer aggregation are roughly the same, approximately 5 X 10(5) M(-1) X(-1) at 20 degrees. Raising or lowering the pH results in a uniform decrease of both aggregation rates due presumably to repulsion of positively charged subunits at acid pH and repulsion of negatively charged subunits at alkaline pH. Addition of p-hydroxymercuribenzoate to alpha chains lowers the rate of monomer aggregation whereas addition of mercurials to the beta subunits appears to lower both the rate of monomer and the rate of dimer aggregation. At high heme concentrations (greater than 10(-5) M) or in the presence of organic phosphates, the rate of chain aggregation becomes limited, in part, by the slow dissociation of beta chain tetramers. In the case of inositol hexaphosphate, the rate of hemoglobin formation exhibits a bell-shaped dependence on phosphate concentration. When intermediate concentrations of inositol hexaphosphate (approximately 10(-4 M) are preincubated with beta subunits, a slow first order time course is observed and exhibits a half-time of about 8 min. As more inositol hexaphosphate is added, the chain aggregation reaction begins to occur more rapidly. Eventually at about 10(-2) M inositol hexaphospate, the time course becomes almost identical to that observed in the absence of phosphates. The increase in the velocity of the chain aggregation reaction at high phosphate concentrations suggests strongly that inositol hexaphosphate binds to beta monomers and, if added in sufficiently large amounts, promotes beta4 dissociation. A quantitative analysis of these results showed that the affinity of beta monomers for inositol hexaphosphate is the same as that of alphabeta dimers. Only when tetramers are formed, either alpha2beta2 or beta4, is a marked increase in affinity for inositol hexaphosphate observed.", "contents": "Aggregation of deoxyhemoglobin subunits. The formation of deoxyhemoglobin was examined by measuring the heme spectral change that accompanies the aggregation of isolated alpha and beta chains. At low hemeconcentrations (less than 10(-5) M), tetramer formation can be described by two consecutive, second order reactions representing the aggregation of monomers followed by the association of alphabeta dimers. At neutral pH, the rates of monomer and dimer aggregation are roughly the same, approximately 5 X 10(5) M(-1) X(-1) at 20 degrees. Raising or lowering the pH results in a uniform decrease of both aggregation rates due presumably to repulsion of positively charged subunits at acid pH and repulsion of negatively charged subunits at alkaline pH. Addition of p-hydroxymercuribenzoate to alpha chains lowers the rate of monomer aggregation whereas addition of mercurials to the beta subunits appears to lower both the rate of monomer and the rate of dimer aggregation. At high heme concentrations (greater than 10(-5) M) or in the presence of organic phosphates, the rate of chain aggregation becomes limited, in part, by the slow dissociation of beta chain tetramers. In the case of inositol hexaphosphate, the rate of hemoglobin formation exhibits a bell-shaped dependence on phosphate concentration. When intermediate concentrations of inositol hexaphosphate (approximately 10(-4 M) are preincubated with beta subunits, a slow first order time course is observed and exhibits a half-time of about 8 min. As more inositol hexaphosphate is added, the chain aggregation reaction begins to occur more rapidly. Eventually at about 10(-2) M inositol hexaphospate, the time course becomes almost identical to that observed in the absence of phosphates. The increase in the velocity of the chain aggregation reaction at high phosphate concentrations suggests strongly that inositol hexaphosphate binds to beta monomers and, if added in sufficiently large amounts, promotes beta4 dissociation. A quantitative analysis of these results showed that the affinity of beta monomers for inositol hexaphosphate is the same as that of alphabeta dimers. Only when tetramers are formed, either alpha2beta2 or beta4, is a marked increase in affinity for inositol hexaphosphate observed."}
{"id": "PMID:12182", "title": "Comparison of the size and physical properties of gamma-glutamyltranspeptidase purified from rat kidney following solubilization with papain or with Triton X-100.", "content": "gamma-Glutamyltranspeptidase is associated with the brush border membrane of kidney proximal straight tubule cells. It can be solubilized qualitatively by treatment with papain or Triton X-100. Neither procedure affects its catalytic activity but the two resulting forms of the enzyme differ considerably in their physical properties. The papain-solubilized transpeptidase is soluble in aqueous buffers and was purified 430-fold. It has an s20,w of 4.9 S, a Stokes radius of 36 A, and a calculated molecular weight of 69,000. It appears homogeneous by sedimentation equilibrium centrifugation (Mr=66,700). In contrast, the Triton-solubilized transpeptidase is soluble only in the presence of detergents and was purifed 300-fold. This form of the enzyme has a Stokes radius of 70 A but an s20,w of only 4.15 S. Aggregation of the enzyme just below the critical micelle concentration of Triton X-100 and its ability to bind 1.16 mg of Triton X-100-protein complex was calculated to be 169,000, but the glycoprotein portion of the complex is 52% of the total mass (87,000). The mass of Triton X-100 (82,000) is consistent with its reported micelle molecular weight. Treatment of the Triton-purified transpeptidase with papain or bromelain results in a form of the enzyme identical in all respects with the papain-purified enzyme. Both the Triton- and papain-purified transpeptidase exhibit two protein bands on sodium lauryl sulfate-polyacrylamide gel electrophoresis. The smaller subunits of the two forms appear identical (Mr=27,000), while the larger subunits of the Triton- and papain-purified enzyme have apparent molecular weights of 54,000 and 51,000, respectively. These data suggest that a peptide (3,000 to 19,000) in the larger subunit of gamma-glutamyltranspeptidase is responsible for its binding to Triton micelles and probably for holding the enzyme in the brush border membrane.", "contents": "Comparison of the size and physical properties of gamma-glutamyltranspeptidase purified from rat kidney following solubilization with papain or with Triton X-100. gamma-Glutamyltranspeptidase is associated with the brush border membrane of kidney proximal straight tubule cells. It can be solubilized qualitatively by treatment with papain or Triton X-100. Neither procedure affects its catalytic activity but the two resulting forms of the enzyme differ considerably in their physical properties. The papain-solubilized transpeptidase is soluble in aqueous buffers and was purified 430-fold. It has an s20,w of 4.9 S, a Stokes radius of 36 A, and a calculated molecular weight of 69,000. It appears homogeneous by sedimentation equilibrium centrifugation (Mr=66,700). In contrast, the Triton-solubilized transpeptidase is soluble only in the presence of detergents and was purifed 300-fold. This form of the enzyme has a Stokes radius of 70 A but an s20,w of only 4.15 S. Aggregation of the enzyme just below the critical micelle concentration of Triton X-100 and its ability to bind 1.16 mg of Triton X-100-protein complex was calculated to be 169,000, but the glycoprotein portion of the complex is 52% of the total mass (87,000). The mass of Triton X-100 (82,000) is consistent with its reported micelle molecular weight. Treatment of the Triton-purified transpeptidase with papain or bromelain results in a form of the enzyme identical in all respects with the papain-purified enzyme. Both the Triton- and papain-purified transpeptidase exhibit two protein bands on sodium lauryl sulfate-polyacrylamide gel electrophoresis. The smaller subunits of the two forms appear identical (Mr=27,000), while the larger subunits of the Triton- and papain-purified enzyme have apparent molecular weights of 54,000 and 51,000, respectively. These data suggest that a peptide (3,000 to 19,000) in the larger subunit of gamma-glutamyltranspeptidase is responsible for its binding to Triton micelles and probably for holding the enzyme in the brush border membrane."}
{"id": "PMID:12183", "title": "Plasma protein synthesis by isolated rat hepatocytes.", "content": "A system of preparation of rat hepatocytes with extended viability has been developed to study the role of hormones and other plasma components upon secretory protein synthesis. Hepatocytes maintained in minimal essential medium reduced the levels of all amino acids in the medium except the slowly catabolized amino acids leucine, isoleucine, and valine, which steadily increase as the result of catabolism of liver protein. Although the liver cells catabolize 10-15% of their own protein during a 20-h incubation, the cells continue to secrete protein in a linear fashion throughout the period. The effects of insulin, cortisol, and epinephrine on general protein synthesis, and specifically on fibrinogen and albumin synthesis, have been tested on cells from both normal rats and adrenalectomized rats. Cells from normal animals show preinduction of tyrosine amino transferase (TAT), having at the time of isolation a high level of enzyme which shows only an increase of approximately 60% upon incubation with cortisol. In contrast, cells from adrenalectomized animals initially have a low level of enzyme which increases fourfold over a period of 9 h. The effects of both epinephrine and cortisol on protein synthesis are also much larger in cells from adrenalectomized animals. After a delay of several hours, cortisol increases fibrinogen synthesis sharply, so that at the end of the 20-h incubation, cells treated with hormone have secreted nearly 2.5 times as much fibrinogen as control cells. The effect is specific; cortisol stimulates neither albumin secretion nor intracellular protein synthesis. The combination of cortisol and epinephrine strongly depresses albumin synthesis in both types of cells. Insulin enhances albumin and general protein synthesis but has little effect on fibrinogen synthesis.", "contents": "Plasma protein synthesis by isolated rat hepatocytes. A system of preparation of rat hepatocytes with extended viability has been developed to study the role of hormones and other plasma components upon secretory protein synthesis. Hepatocytes maintained in minimal essential medium reduced the levels of all amino acids in the medium except the slowly catabolized amino acids leucine, isoleucine, and valine, which steadily increase as the result of catabolism of liver protein. Although the liver cells catabolize 10-15% of their own protein during a 20-h incubation, the cells continue to secrete protein in a linear fashion throughout the period. The effects of insulin, cortisol, and epinephrine on general protein synthesis, and specifically on fibrinogen and albumin synthesis, have been tested on cells from both normal rats and adrenalectomized rats. Cells from normal animals show preinduction of tyrosine amino transferase (TAT), having at the time of isolation a high level of enzyme which shows only an increase of approximately 60% upon incubation with cortisol. In contrast, cells from adrenalectomized animals initially have a low level of enzyme which increases fourfold over a period of 9 h. The effects of both epinephrine and cortisol on protein synthesis are also much larger in cells from adrenalectomized animals. After a delay of several hours, cortisol increases fibrinogen synthesis sharply, so that at the end of the 20-h incubation, cells treated with hormone have secreted nearly 2.5 times as much fibrinogen as control cells. The effect is specific; cortisol stimulates neither albumin secretion nor intracellular protein synthesis. The combination of cortisol and epinephrine strongly depresses albumin synthesis in both types of cells. Insulin enhances albumin and general protein synthesis but has little effect on fibrinogen synthesis."}
{"id": "PMID:12184", "title": "Differential binding of methyl benzimidazol-2-yl carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans.", "content": "The antimitotic compound methyl benzimidazol-2-yl carbamate (MBC) formed a complex in vitro with a protein present in mycelial extracts of fungi. The binding protein of Aspergillus nidulans showed a set of properties which is unique for tubulin. Binding occurred rapidly at 4 degrees C and was competitively inhibited by oncodazole and colchicine. Other inhibitors of microtubule function such as podophyllotoxin, vinblastine sulfate, melatonin, and griseofulvin did not interfere with binding of MBC. Electrophoretic analysis of partially purified preparations of the binding protein revealed the presence of proteins with similar mobilities as mammalian tubulin monomers. Hence it is concluded that the binding protein is identical with fungal tubulin. The effect of MBC on mycelial growth of mutant strains of A. nidulans was positively correlated with the affinity of the binding sites for this compound. The apparent binding constant for MBC and tubulin from a wild type was estimated at 4.5 X 10(5), from a resistant strain at 3.7 X 10(4), and from a strain with increased sensitivity to MBC at 1.6 X 10(6) liters/mol. Mutants showing resistance and increased sensitivity to MBC are candidates to have alterations in tubulin structure. Affinity of tubulin for MBC is probably a common mechanism of resistance to this compound in fungi. Low affinity of tubulin for MBC is probably a common mechanism of resistance binding constant of 2.5 X 10(3) liters/mol.", "contents": "Differential binding of methyl benzimidazol-2-yl carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans. The antimitotic compound methyl benzimidazol-2-yl carbamate (MBC) formed a complex in vitro with a protein present in mycelial extracts of fungi. The binding protein of Aspergillus nidulans showed a set of properties which is unique for tubulin. Binding occurred rapidly at 4 degrees C and was competitively inhibited by oncodazole and colchicine. Other inhibitors of microtubule function such as podophyllotoxin, vinblastine sulfate, melatonin, and griseofulvin did not interfere with binding of MBC. Electrophoretic analysis of partially purified preparations of the binding protein revealed the presence of proteins with similar mobilities as mammalian tubulin monomers. Hence it is concluded that the binding protein is identical with fungal tubulin. The effect of MBC on mycelial growth of mutant strains of A. nidulans was positively correlated with the affinity of the binding sites for this compound. The apparent binding constant for MBC and tubulin from a wild type was estimated at 4.5 X 10(5), from a resistant strain at 3.7 X 10(4), and from a strain with increased sensitivity to MBC at 1.6 X 10(6) liters/mol. Mutants showing resistance and increased sensitivity to MBC are candidates to have alterations in tubulin structure. Affinity of tubulin for MBC is probably a common mechanism of resistance to this compound in fungi. Low affinity of tubulin for MBC is probably a common mechanism of resistance binding constant of 2.5 X 10(3) liters/mol."}
{"id": "PMID:12186", "title": "[Ultra-selective vagotomy in the treatment of duodenal ulcer. Report on the round table discussion (77th French Surgery Congress, 1975)].", "content": "This panel enables us to draw following conclusions on highly selective vagotomy for duodenal ulcer: --One fact seems to be sure: H.S.V. is a benign and efficient operation over short and average periods of time, providing that some technical requirements are observed. --However some points are still under discussion and much debated: --the useful purpose of per-operative tests; --the more or less frequent addition of drainage procedure. --Lastly, long-term anti-ulcerous efficiency (over 5 years) is still not known precisely; some think that the risk of vagal regeneration are greater after this type of vagotomy.", "contents": "[Ultra-selective vagotomy in the treatment of duodenal ulcer. Report on the round table discussion (77th French Surgery Congress, 1975)]. This panel enables us to draw following conclusions on highly selective vagotomy for duodenal ulcer: --One fact seems to be sure: H.S.V. is a benign and efficient operation over short and average periods of time, providing that some technical requirements are observed. --However some points are still under discussion and much debated: --the useful purpose of per-operative tests; --the more or less frequent addition of drainage procedure. --Lastly, long-term anti-ulcerous efficiency (over 5 years) is still not known precisely; some think that the risk of vagal regeneration are greater after this type of vagotomy."}
{"id": "PMID:12187", "title": "Chromatographic characterization of phenothiazine drugs by a reversed-phase thin-layer technique.", "content": "A reversed-phase thin-layer chromatographic technique was used for the characterization of 26 phenothiazine drugs. With two chromatographic systems having the sam stationary phase and phase volume ratio, but mobile phases of different pH, all but two of the compounds could be identified. Rf values in the different systems were standardized by applying a reference compound to the plates next to each compound under investigation; the corrected Rf values were calculated from the differences in the Rm values of the compounds and the reference compound, and the theoretical Rm value of the reference. It was shown that Rf values for different chromatographic systems with the same stationary phase could be predicted with reasonable accuracy. The pH of the mobile phase, for which a maximum difference in Rf values was obtained for pairs of compounds, could also be calculated and corresponded well with the observed values.", "contents": "Chromatographic characterization of phenothiazine drugs by a reversed-phase thin-layer technique. A reversed-phase thin-layer chromatographic technique was used for the characterization of 26 phenothiazine drugs. With two chromatographic systems having the sam stationary phase and phase volume ratio, but mobile phases of different pH, all but two of the compounds could be identified. Rf values in the different systems were standardized by applying a reference compound to the plates next to each compound under investigation; the corrected Rf values were calculated from the differences in the Rm values of the compounds and the reference compound, and the theoretical Rm value of the reference. It was shown that Rf values for different chromatographic systems with the same stationary phase could be predicted with reasonable accuracy. The pH of the mobile phase, for which a maximum difference in Rf values was obtained for pairs of compounds, could also be calculated and corresponded well with the observed values."}
{"id": "PMID:12188", "title": "Use of acetonitrile for the extraction of herbicide residues from soils.", "content": "Using a 10% aqueous acetonitrile solution for extraction and an identical solvent clean-up procedure, soil-based residues of the herbicides alachlor, benzoyl-prop-ethyl, flufenprop-isopropyl, flufenprop-methyl, dichlorfop-methyl, nitrofen, and profluralin were recovered reproducibly from three prairie soils fortified at 0.5 and 0.1 ppm levels. The acidic herbicides benazolin, 2,4-D, and 2,4,5-T, together with the acids derived from benzoylprop-ethyl, dichlorfop-methyl, flufenprop-isopropyl, and flufenprop-methyl were reproducibly recovered from the three prairie soils fortified at 0.5 and 0.1 ppm levels using 30% aqueous acetonitrile containing 1% acetic acid after identical clean-up stages. All compounds were analysed by gas chromatographic means utilising an electron-capture detector. The two procedures described were developed for the routine extraction and analysis of neutral and acidic herbicide residues from field soil persistence studies.", "contents": "Use of acetonitrile for the extraction of herbicide residues from soils. Using a 10% aqueous acetonitrile solution for extraction and an identical solvent clean-up procedure, soil-based residues of the herbicides alachlor, benzoyl-prop-ethyl, flufenprop-isopropyl, flufenprop-methyl, dichlorfop-methyl, nitrofen, and profluralin were recovered reproducibly from three prairie soils fortified at 0.5 and 0.1 ppm levels. The acidic herbicides benazolin, 2,4-D, and 2,4,5-T, together with the acids derived from benzoylprop-ethyl, dichlorfop-methyl, flufenprop-isopropyl, and flufenprop-methyl were reproducibly recovered from the three prairie soils fortified at 0.5 and 0.1 ppm levels using 30% aqueous acetonitrile containing 1% acetic acid after identical clean-up stages. All compounds were analysed by gas chromatographic means utilising an electron-capture detector. The two procedures described were developed for the routine extraction and analysis of neutral and acidic herbicide residues from field soil persistence studies."}
{"id": "PMID:12189", "title": "High-pressure liquid chromatography of cannabis. Quantitative analysis of acidic and neutral cannabinoids.", "content": "A reversed-phase high-pressure liquid chromatographic method has been developed for the simultaneous analysis of the acidic and neutral cannabinoids in cannabis. Cannabigerol and cannabigerolic acid have been located in the liquid chromatogram of cannabis and factors affecting the chromatographic process are discussed. A method for quantitating one component in the presence of a second unresolved component is described.", "contents": "High-pressure liquid chromatography of cannabis. Quantitative analysis of acidic and neutral cannabinoids. A reversed-phase high-pressure liquid chromatographic method has been developed for the simultaneous analysis of the acidic and neutral cannabinoids in cannabis. Cannabigerol and cannabigerolic acid have been located in the liquid chromatogram of cannabis and factors affecting the chromatographic process are discussed. A method for quantitating one component in the presence of a second unresolved component is described."}
{"id": "PMID:12190", "title": "Residual anionic properties of a covalently substituted controlled-pore glass, glyceryl-CPG.", "content": "A commercial controlled-pore glass medium for exclusion chromatography which is substituted with glycerol to eliminate non-specific adsorption (Glyceryl-CPG) was examined. Experiments on the elution of acetylcholinesterase and ganglioside micelles at varied ionic strength and pH showed that a slight anionic character still persisted on the glass matrix. At ionic strengths above 0.1, this had no effect on the elution of proteins. The material was found to have no tendency to adsorb proteins and other compounds, and was judged an excellent medium for exclusion chromatography. As a support for affinity chromatography, Glyceryl-CPG could be activated by periodate to form a virtually neutral matrix-ligand system.", "contents": "Residual anionic properties of a covalently substituted controlled-pore glass, glyceryl-CPG. A commercial controlled-pore glass medium for exclusion chromatography which is substituted with glycerol to eliminate non-specific adsorption (Glyceryl-CPG) was examined. Experiments on the elution of acetylcholinesterase and ganglioside micelles at varied ionic strength and pH showed that a slight anionic character still persisted on the glass matrix. At ionic strengths above 0.1, this had no effect on the elution of proteins. The material was found to have no tendency to adsorb proteins and other compounds, and was judged an excellent medium for exclusion chromatography. As a support for affinity chromatography, Glyceryl-CPG could be activated by periodate to form a virtually neutral matrix-ligand system."}
{"id": "PMID:12191", "title": "Inhibition of human plasma renin activity by pepstatin.", "content": "Pepstatin, a pentapeptide isolated from streptomyces, is a powerful inhibitor of several acid proteases. Its ability to inhibit the renin-angiotensinogen reaction was studied in vitro, in various human plasma. A 50% inhibition of plasma renin activity was obtained with 10(-6)M pepstatin at pH 5.7 and 10(-5)M at pH 7.4. The inhibition of plasma renin activity by pepstatin was studied in hypertensive patients with various plasma renin levels. The inhibitory effect could be demonstrated in patients with low, normal and high renin activity at both pH's. The type of inhibition and the inhibitory constant were investigated by Dixon plot and Lineweaver-Burk plot in three separate experiments. On both representations, a competitive type of inhibition was found with an inhibitory constant of about 1.2 x 10(-6)M.", "contents": "Inhibition of human plasma renin activity by pepstatin. Pepstatin, a pentapeptide isolated from streptomyces, is a powerful inhibitor of several acid proteases. Its ability to inhibit the renin-angiotensinogen reaction was studied in vitro, in various human plasma. A 50% inhibition of plasma renin activity was obtained with 10(-6)M pepstatin at pH 5.7 and 10(-5)M at pH 7.4. The inhibition of plasma renin activity by pepstatin was studied in hypertensive patients with various plasma renin levels. The inhibitory effect could be demonstrated in patients with low, normal and high renin activity at both pH's. The type of inhibition and the inhibitory constant were investigated by Dixon plot and Lineweaver-Burk plot in three separate experiments. On both representations, a competitive type of inhibition was found with an inhibitory constant of about 1.2 x 10(-6)M."}
{"id": "PMID:12192", "title": "Adaptive responses of brain cyclic AMP-generating systems to alterations in synaptic input.", "content": "The concept of subsensitivity and supersensitivity as a mechanism of neuronal adaptation to alterations in synaptic activity in the brain is an attractive one. However, the complexity of the central nervous system has made it difficult to determine the cellular basis of apparent changes in neuronal excitability resulting from alterations in synaptic input (cf. ref. 83). It now seems that, at least for inhibitory central pathways in which cyclic AMP-generating systems mediate postsynaptic receptor-responses, alterations in synaptic input lead in rat cortex to predictable super- or subsensitivity of the norepinephrine-sensitive cyclic AMP-systems. Supersensitivity of histamine-sensitive cyclic AMP-systems also occurs in rat cortex as a result of apparent lesions of histaminergic tracts. The reason that supersensitivity does not develop to norepinephrine and histamine in guinea pig cortex after similar \"denervations\" is not known, but is central to an understanding of the factors involved in the role of cyclic AMP-mechanisms to the adaptive plasticity of the central nervous system. However, even before an understanding of all the factors involved in alterations in cyclic AMP-responses in brain tissue is obtained, studies on the effects of environmental and drug-manipulations can provide insights both into the central roles for cyclic AMP-mechanisms and into the nature of drug action. Clearly, an understanding of the interelationships of synaptic input and adaptive changes in postsynaptic cyclic AMP-systems and the exploitation of such knowledge for the elucidation of central adaptive function is an exciting challenge for future research.", "contents": "Adaptive responses of brain cyclic AMP-generating systems to alterations in synaptic input. The concept of subsensitivity and supersensitivity as a mechanism of neuronal adaptation to alterations in synaptic activity in the brain is an attractive one. However, the complexity of the central nervous system has made it difficult to determine the cellular basis of apparent changes in neuronal excitability resulting from alterations in synaptic input (cf. ref. 83). It now seems that, at least for inhibitory central pathways in which cyclic AMP-generating systems mediate postsynaptic receptor-responses, alterations in synaptic input lead in rat cortex to predictable super- or subsensitivity of the norepinephrine-sensitive cyclic AMP-systems. Supersensitivity of histamine-sensitive cyclic AMP-systems also occurs in rat cortex as a result of apparent lesions of histaminergic tracts. The reason that supersensitivity does not develop to norepinephrine and histamine in guinea pig cortex after similar \"denervations\" is not known, but is central to an understanding of the factors involved in the role of cyclic AMP-mechanisms to the adaptive plasticity of the central nervous system. However, even before an understanding of all the factors involved in alterations in cyclic AMP-responses in brain tissue is obtained, studies on the effects of environmental and drug-manipulations can provide insights both into the central roles for cyclic AMP-mechanisms and into the nature of drug action. Clearly, an understanding of the interelationships of synaptic input and adaptive changes in postsynaptic cyclic AMP-systems and the exploitation of such knowledge for the elucidation of central adaptive function is an exciting challenge for future research."}
{"id": "PMID:12194", "title": "Enhancement of methacholine-stimulated guanosine 3':5'-cyclic monophosphate formation in supersensitive guinea pig vasa deferentia.", "content": "Decentralization of the guinea pig vas deferens resulted in supersensitivity of the contractile response to methacholine. Methacholine also elevated cyclic GMP to a greater extent in the decentralized vas deferens than in sham-operated controls. Decentralization did not alter basal cyclic AMP or cyclic GMP content. These observations are analogous to the enhanced responsiveness of cyclic AMP formation in supersensitive beta adrenergic systems.", "contents": "Enhancement of methacholine-stimulated guanosine 3':5'-cyclic monophosphate formation in supersensitive guinea pig vasa deferentia. Decentralization of the guinea pig vas deferens resulted in supersensitivity of the contractile response to methacholine. Methacholine also elevated cyclic GMP to a greater extent in the decentralized vas deferens than in sham-operated controls. Decentralization did not alter basal cyclic AMP or cyclic GMP content. These observations are analogous to the enhanced responsiveness of cyclic AMP formation in supersensitive beta adrenergic systems."}
{"id": "PMID:12193", "title": "Inhibition of mammalian soluble guanylate cyclase activity by adenosine 5'-tetraphosphate, guanosine 5'-tetraphosphate and other nucleotides.", "content": "The effects of a variety of purine and pyrimidine nucleotides were tested for their capacity to inhibit mammalian soluble guanylate cyclase activity. Adenosine 5'-tetraphosphate (ATetP), ATP, ADP, AMP, guanosine 5'-tetraphosphate (GTetP) and GDP were found to inhibit soluble guanylate cyclase activity from rat lung and other mammalian tissues. The corresponding cytosine and thymine nucleotides showed little or no inhibitory activity, except for thymidine 5'-tetraphosphate, which inhibited glanylate cyclase activity but to a lesser extent than did the purine nucleoside tetraphosphates. ATetP and GTetP were found to be potent inhibitors of soluble guanylate cyclase activity from rat, guinea pig and mouse lung, rat heart and rat brain. Both purine nucleoside tetraphosphates were competitive inhibitors of the rat lung soluble enzyme. ATetP and GTetP had Ki values of 1 muM and 2.5 muM, respectively. The experimental data suggest that purine nucleoside tetraphosphates, and perhaps other purine nucleotides, may play a biologic role in modulating mammalian soluble guanylate cyclase activity.", "contents": "Inhibition of mammalian soluble guanylate cyclase activity by adenosine 5'-tetraphosphate, guanosine 5'-tetraphosphate and other nucleotides. The effects of a variety of purine and pyrimidine nucleotides were tested for their capacity to inhibit mammalian soluble guanylate cyclase activity. Adenosine 5'-tetraphosphate (ATetP), ATP, ADP, AMP, guanosine 5'-tetraphosphate (GTetP) and GDP were found to inhibit soluble guanylate cyclase activity from rat lung and other mammalian tissues. The corresponding cytosine and thymine nucleotides showed little or no inhibitory activity, except for thymidine 5'-tetraphosphate, which inhibited glanylate cyclase activity but to a lesser extent than did the purine nucleoside tetraphosphates. ATetP and GTetP were found to be potent inhibitors of soluble guanylate cyclase activity from rat, guinea pig and mouse lung, rat heart and rat brain. Both purine nucleoside tetraphosphates were competitive inhibitors of the rat lung soluble enzyme. ATetP and GTetP had Ki values of 1 muM and 2.5 muM, respectively. The experimental data suggest that purine nucleoside tetraphosphates, and perhaps other purine nucleotides, may play a biologic role in modulating mammalian soluble guanylate cyclase activity."}
{"id": "PMID:12195", "title": "Enhancement of the antiplaque value of antibacterial agents through enamel-conditioning methods: II. Acquisition of antiplaque properties by treated enamel.", "content": "Enamel specimens treated with systems containing enamel conditioners and antibacterial agents have previously been shown to incorporate the latter into the enamel. It has now been demonstrated that enamel blocks treated with these systems become highly resistant to bacterial colonization, that this effect is rather long lasting, and that the treated specimens prevent acid formation when incubated with Streptococcus mutans in a sugar-containing medium.", "contents": "Enhancement of the antiplaque value of antibacterial agents through enamel-conditioning methods: II. Acquisition of antiplaque properties by treated enamel. Enamel specimens treated with systems containing enamel conditioners and antibacterial agents have previously been shown to incorporate the latter into the enamel. It has now been demonstrated that enamel blocks treated with these systems become highly resistant to bacterial colonization, that this effect is rather long lasting, and that the treated specimens prevent acid formation when incubated with Streptococcus mutans in a sugar-containing medium."}
{"id": "PMID:12204", "title": "The systemic use of procaine in the treatment of the elderly: a review.", "content": "This article is a review and evaluation of the world literature on the systemic use of procaine in the treatment of the aging process and the common chronic diseases of later life. Included are data from 285 articles and books, describing treatment in more than 100,000 patients in the past 25 years. Except for a possible antidepressant effect, there is no convincing evidence that procaine (or Gerovital, of which procaine is the major component) has any value in the treatment of disease in older patients. If procaine has an antidepressant effect, there is some likelihood that this accounts for the reports of decreased complaints referable to the musculoskeletal, cardiovascular, endocrine sexual, gastrointestinal and respiratory systems.", "contents": "The systemic use of procaine in the treatment of the elderly: a review. This article is a review and evaluation of the world literature on the systemic use of procaine in the treatment of the aging process and the common chronic diseases of later life. Included are data from 285 articles and books, describing treatment in more than 100,000 patients in the past 25 years. Except for a possible antidepressant effect, there is no convincing evidence that procaine (or Gerovital, of which procaine is the major component) has any value in the treatment of disease in older patients. If procaine has an antidepressant effect, there is some likelihood that this accounts for the reports of decreased complaints referable to the musculoskeletal, cardiovascular, endocrine sexual, gastrointestinal and respiratory systems."}
{"id": "PMID:12205", "title": "[Diagnosis of fetal distress during labor with the aid of the Hammacher cardio-tocographic score and fetal pH determination].", "content": "The authors study the value of the Hammacher tocographic scoring system in the diagnosis of fetal distress in labour. This score gives equal value to three components of the fetal heart rate: the base line, transient variations (dips) and fluctuations (oscillations). There is a statistically very significant (p less than 0.001) relationship between the cardio-tocographic score and the fetal pH as has been found in 106 labours with a coefficient of correlation of 0.67. The score can only be carried out usefully when a \"beat to beat\" to heart rate is registered and when this is not influenced by the administration of drugs to the mother. The score has been demonstrated to be particularly useful in the diagnosis of fetal distress when the membranes are still intact.", "contents": "[Diagnosis of fetal distress during labor with the aid of the Hammacher cardio-tocographic score and fetal pH determination]. The authors study the value of the Hammacher tocographic scoring system in the diagnosis of fetal distress in labour. This score gives equal value to three components of the fetal heart rate: the base line, transient variations (dips) and fluctuations (oscillations). There is a statistically very significant (p less than 0.001) relationship between the cardio-tocographic score and the fetal pH as has been found in 106 labours with a coefficient of correlation of 0.67. The score can only be carried out usefully when a \"beat to beat\" to heart rate is registered and when this is not influenced by the administration of drugs to the mother. The score has been demonstrated to be particularly useful in the diagnosis of fetal distress when the membranes are still intact."}
{"id": "PMID:12206", "title": "[The risk of cardiac arrest during laparoscopy. A study of 50,000 laparoscopies and animal experimentation].", "content": "In a French national enquiry into 50,000 laparoscopies it emerges that the number of cardiac arrests works out at 1 in 2,000. The percentage of reversible cardiac arrests was 1 in 2500 and of irreversible cardiac arrests 1.2 in 10,000. 25 cases were studied in great detail, both clinically and physiopathologically. This was thanks to a very full questionnaire most kindly filled up by those who had told us that this type of accident had happened in their practice. The physiopathogenesis of circulatory arrests during laparoscopy is complex. It appears however that among the different potentiating factors are changes in haemodynamics and biological changes that give rise to the greatest risks. Experimental work carried out with a long-tailed baboon was performed by the authors with the idea on the one hand of confirming that haemodynamic and biological troubles resulting from the pneumoperitoneum were important and on the other hand of analysing the changes in detail and of working out prophylactic principles for the anaesthetist and the laparoscopist.", "contents": "[The risk of cardiac arrest during laparoscopy. A study of 50,000 laparoscopies and animal experimentation]. In a French national enquiry into 50,000 laparoscopies it emerges that the number of cardiac arrests works out at 1 in 2,000. The percentage of reversible cardiac arrests was 1 in 2500 and of irreversible cardiac arrests 1.2 in 10,000. 25 cases were studied in great detail, both clinically and physiopathologically. This was thanks to a very full questionnaire most kindly filled up by those who had told us that this type of accident had happened in their practice. The physiopathogenesis of circulatory arrests during laparoscopy is complex. It appears however that among the different potentiating factors are changes in haemodynamics and biological changes that give rise to the greatest risks. Experimental work carried out with a long-tailed baboon was performed by the authors with the idea on the one hand of confirming that haemodynamic and biological troubles resulting from the pneumoperitoneum were important and on the other hand of analysing the changes in detail and of working out prophylactic principles for the anaesthetist and the laparoscopist."}
{"id": "PMID:12234", "title": "Human epidermal transglutaminase. II. Immunologic properties.", "content": "A monospecific antibody for human epidermal transglutaminase was prepared in rabbits. The antibody formed single immunoprecipitin lines with purified or crude human transglutaminases and quantitatively precipitated transglutaminase activity. There were no precipitin reactions between human factor XIII (zymogen or active enzyme) and antihuman epidermal transglutaminase or between human epidermal transglutaminase and antihuman factor XIII. Heating epidermal transglutaminase (56 degrees C, 15 min) in the presence of calcium increased the enzyme activity up to 10 times baseline levels. The heat-activated human epidermal transglutaminase was identical by immunodiffusion with the native enzyme, although slightly higher precipitation titers were detected following heating. There was no cross-reaction of antihuman epidermal transglutaminase with frog, rat, mouse, chicken, or human hair follicle transglutaminases.", "contents": "Human epidermal transglutaminase. II. Immunologic properties. A monospecific antibody for human epidermal transglutaminase was prepared in rabbits. The antibody formed single immunoprecipitin lines with purified or crude human transglutaminases and quantitatively precipitated transglutaminase activity. There were no precipitin reactions between human factor XIII (zymogen or active enzyme) and antihuman epidermal transglutaminase or between human epidermal transglutaminase and antihuman factor XIII. Heating epidermal transglutaminase (56 degrees C, 15 min) in the presence of calcium increased the enzyme activity up to 10 times baseline levels. The heat-activated human epidermal transglutaminase was identical by immunodiffusion with the native enzyme, although slightly higher precipitation titers were detected following heating. There was no cross-reaction of antihuman epidermal transglutaminase with frog, rat, mouse, chicken, or human hair follicle transglutaminases."}
{"id": "PMID:12235", "title": "Interactions between viruses and bacteria in patients with chronic bronchitis.", "content": "The possibility that viral infections of the respiratory tract might predispose to bacterial colonization or infection was studied in 120 patients with chronic obstructive pulmonary disease and 30 control subjects; these individuals were observed for seven years. The ratio of the number of observed to the number of expected associations between viruses and bacteria was 2.43 (P = 0.037) for the pair influenza virus and Streptococcus pneumoniae and was 2.06 (P = 0.056) for influenza virus and Haemophilus influenzae. Consistently positive, but not significant, associations were detected between rhinovirus and herpes simplex virus infections and isolations of S. pneumoniae and H. influenzae. In contrast, isolations of the nonpathogenic Haemophilus parainfluenzae could not be related to prior viral infections. Significant rises in titer of antibody to H. influenzae were detected on 76 occasions, and 20 (26%) of these antibody rises were associated with viral or mycoplasmal infections during the preceding 120 days. The expected number of such associations was 8.34 (ratio of number observed to number expected, 2.40; P = 0.08). These results suggest that viral infections of the respiratory tract in patients with chronic obstructive pulmonary disease are associated with increased colonization by potentially pathogenic bacteria and may also predispose to infections with H. influenzae.", "contents": "Interactions between viruses and bacteria in patients with chronic bronchitis. The possibility that viral infections of the respiratory tract might predispose to bacterial colonization or infection was studied in 120 patients with chronic obstructive pulmonary disease and 30 control subjects; these individuals were observed for seven years. The ratio of the number of observed to the number of expected associations between viruses and bacteria was 2.43 (P = 0.037) for the pair influenza virus and Streptococcus pneumoniae and was 2.06 (P = 0.056) for influenza virus and Haemophilus influenzae. Consistently positive, but not significant, associations were detected between rhinovirus and herpes simplex virus infections and isolations of S. pneumoniae and H. influenzae. In contrast, isolations of the nonpathogenic Haemophilus parainfluenzae could not be related to prior viral infections. Significant rises in titer of antibody to H. influenzae were detected on 76 occasions, and 20 (26%) of these antibody rises were associated with viral or mycoplasmal infections during the preceding 120 days. The expected number of such associations was 8.34 (ratio of number observed to number expected, 2.40; P = 0.08). These results suggest that viral infections of the respiratory tract in patients with chronic obstructive pulmonary disease are associated with increased colonization by potentially pathogenic bacteria and may also predispose to infections with H. influenzae."}
{"id": "PMID:12236", "title": "Experimental otitis media due to Streptococcus pneumoniae: immunopathogenic response in the chinchilla.", "content": "Acute otitis media was produced in 110 chinchillas by inoculation of type 23 Streptococcus pneumoniae directly into the middle ear cavity by tympanotomy. During the first three days after inoculation, inflammatory cells were seen in the mucoperiosteum of the middle ear. After four to seven days, there was purulent exudation in the middle ear cavity, and 40% of the animals had pneumococcal meningitis and/or bacteremia. The middle ears were sterile in five of 28 animals sacrificed during the second week and in six of seven animals sacrificed at six weeks, although subepithelial changes persisted in the mucoperiosteum. Levels of antibody to S. pneumoniae in serum were measured by radioimmunoassay; mean values were 6.1 ng of pneumococcal antibody nitrogen/ml in 28 uninfected control animals and 16.5 ng of antibody nitrogen/ml in 29 animals sacrificed two weeks after inoculation (P less than 0.025). Opsonic activity of serum against S. pneumoniae was evaluated in infected and uninfected chinchillas. The opsonic titer was significantly higher in infected animals sacrificed at six weeks than in uninfected controls. Although pneumococcal polysaccharide antigen was found by counterimmunoelectrophoresis in 25 of 30 middle ear effusions, it could not be detected in the serum from infected animals. Methods for infection and sacrifice of chinchillas yielded reproducible results. This model should permit evaluation of the pathologic response to other serotypes of S. pneumoniae and possibly to prophylactic and therapeutic regimes.", "contents": "Experimental otitis media due to Streptococcus pneumoniae: immunopathogenic response in the chinchilla. Acute otitis media was produced in 110 chinchillas by inoculation of type 23 Streptococcus pneumoniae directly into the middle ear cavity by tympanotomy. During the first three days after inoculation, inflammatory cells were seen in the mucoperiosteum of the middle ear. After four to seven days, there was purulent exudation in the middle ear cavity, and 40% of the animals had pneumococcal meningitis and/or bacteremia. The middle ears were sterile in five of 28 animals sacrificed during the second week and in six of seven animals sacrificed at six weeks, although subepithelial changes persisted in the mucoperiosteum. Levels of antibody to S. pneumoniae in serum were measured by radioimmunoassay; mean values were 6.1 ng of pneumococcal antibody nitrogen/ml in 28 uninfected control animals and 16.5 ng of antibody nitrogen/ml in 29 animals sacrificed two weeks after inoculation (P less than 0.025). Opsonic activity of serum against S. pneumoniae was evaluated in infected and uninfected chinchillas. The opsonic titer was significantly higher in infected animals sacrificed at six weeks than in uninfected controls. Although pneumococcal polysaccharide antigen was found by counterimmunoelectrophoresis in 25 of 30 middle ear effusions, it could not be detected in the serum from infected animals. Methods for infection and sacrifice of chinchillas yielded reproducible results. This model should permit evaluation of the pathologic response to other serotypes of S. pneumoniae and possibly to prophylactic and therapeutic regimes."}
{"id": "PMID:12239", "title": "Inhibition of vitamin B12 binding to transcobalamin II at low pH: basis of a procedure for quantitation of circulating TC II and R binders.", "content": "A diminution in the binding of exogenous vitamin B12 by serum or plasma at pH 1.5 to 2 (acid-resistant binding capacity, ARBC) as compared with the binding capacity at neutral pH (unsaturated vitamin B12 binding capacity, UBBC) was observed. This phenomenon was found to be attributable to the absence of transcobalamin II (TC II)-associated vitamin B12 from serum labeled at low pH, as demonstrated by gel chromatography on Sephadex G-200. Further confirmation was obtained by demonstration of a significant correlation between the ARBC and the R binder content, quantitated as resistance to precipitation by ammonium sulfate at a 2M concentration. Serum labeled at acid pH failed to deliver vitamin B12 to Hela cells indicating absence of a \"functional\" TC II-B12 complex. The differing vitamin B12 binding capacities of neutral and acidified material was utilized to fractionate the unsaturated vitamin B12-binding proteins of serum and plasma. The ARBC was used to measure the R binder content, and TC II was calculated from the difference between UBBC and ARBC. The fractionation procedure was performed on 75 sera and showed increased ARBC in patients with myeloproliferative disorders and decreased ARBC in leukopenia. The content of unsaturated vitamin B12-binding protein was compared in 75 paired samples of serum and plasma collected from EDTA-anticoagulated blood containing sodium fluoride to inhibit release of granulocyte binders. The ARBC content of fluoridated plasma was significantly lower, due to decreased in vitro R binder release. Plasma also contained less TC II, possibly related to in vitro cellular uptake of this binder in fluoridated plasma.", "contents": "Inhibition of vitamin B12 binding to transcobalamin II at low pH: basis of a procedure for quantitation of circulating TC II and R binders. A diminution in the binding of exogenous vitamin B12 by serum or plasma at pH 1.5 to 2 (acid-resistant binding capacity, ARBC) as compared with the binding capacity at neutral pH (unsaturated vitamin B12 binding capacity, UBBC) was observed. This phenomenon was found to be attributable to the absence of transcobalamin II (TC II)-associated vitamin B12 from serum labeled at low pH, as demonstrated by gel chromatography on Sephadex G-200. Further confirmation was obtained by demonstration of a significant correlation between the ARBC and the R binder content, quantitated as resistance to precipitation by ammonium sulfate at a 2M concentration. Serum labeled at acid pH failed to deliver vitamin B12 to Hela cells indicating absence of a \"functional\" TC II-B12 complex. The differing vitamin B12 binding capacities of neutral and acidified material was utilized to fractionate the unsaturated vitamin B12-binding proteins of serum and plasma. The ARBC was used to measure the R binder content, and TC II was calculated from the difference between UBBC and ARBC. The fractionation procedure was performed on 75 sera and showed increased ARBC in patients with myeloproliferative disorders and decreased ARBC in leukopenia. The content of unsaturated vitamin B12-binding protein was compared in 75 paired samples of serum and plasma collected from EDTA-anticoagulated blood containing sodium fluoride to inhibit release of granulocyte binders. The ARBC content of fluoridated plasma was significantly lower, due to decreased in vitro R binder release. Plasma also contained less TC II, possibly related to in vitro cellular uptake of this binder in fluoridated plasma."}
{"id": "PMID:12240", "title": "Properties and development of erythropoietic stem cells in the chick embryo.", "content": "1. When injected into irradiated chickens, haemopoietic stem cells give rise to well-defined erythrocytic colonies in the host marrow. Such stem cells (CFU-M = Colony Forming Unit in Marrow) have been found in different tissue of the chicke embryo (yolk sac, blood, marrow). Analysis of the properties of CFU-M reveals that they represent two classes of stem cells: pluripotent stem cells mainly in adult marrow and erythrocytic-committed stem cells present in yolk sac. 2. Yolk sac contains the main pool of CFU-M during the major part of embryonic life. In the blood of 6-day-old embryo, there are three or four times more CFU-Ms than in the yolk sac; they are no longer detected in the blood after the 16th day of incubation. During development of the marrow, stem cells are actively differentiating and their total number remains the same from 16 days to hatching.", "contents": "Properties and development of erythropoietic stem cells in the chick embryo. 1. When injected into irradiated chickens, haemopoietic stem cells give rise to well-defined erythrocytic colonies in the host marrow. Such stem cells (CFU-M = Colony Forming Unit in Marrow) have been found in different tissue of the chicke embryo (yolk sac, blood, marrow). Analysis of the properties of CFU-M reveals that they represent two classes of stem cells: pluripotent stem cells mainly in adult marrow and erythrocytic-committed stem cells present in yolk sac. 2. Yolk sac contains the main pool of CFU-M during the major part of embryonic life. In the blood of 6-day-old embryo, there are three or four times more CFU-Ms than in the yolk sac; they are no longer detected in the blood after the 16th day of incubation. During development of the marrow, stem cells are actively differentiating and their total number remains the same from 16 days to hatching."}
{"id": "PMID:12241", "title": "Temperature acclimation and oxygen-binding properties of blood and multiple haemoglobins of rainbow trout.", "content": "Acclimation of rainbow trout to 5, 15 and 22 degrees C for periods exceeding 4 months had no significant effect on the oxygen affinity of whole blood or on the concentration of ATP, which is the main organic phosphate in red cells. Slight differences were, however, found in the oxygenation properties of the haemolysates, which correlate with changes in the relative concentration of the multiple haemoglobins. The oxygen-binding properties of the main haemoglobin components account for the observed differences in the haemolysates. The possible thermoacclimatory significance of changes in haemoglobin multiplicity and co-factor concentrations is discussed.", "contents": "Temperature acclimation and oxygen-binding properties of blood and multiple haemoglobins of rainbow trout. Acclimation of rainbow trout to 5, 15 and 22 degrees C for periods exceeding 4 months had no significant effect on the oxygen affinity of whole blood or on the concentration of ATP, which is the main organic phosphate in red cells. Slight differences were, however, found in the oxygenation properties of the haemolysates, which correlate with changes in the relative concentration of the multiple haemoglobins. The oxygen-binding properties of the main haemoglobin components account for the observed differences in the haemolysates. The possible thermoacclimatory significance of changes in haemoglobin multiplicity and co-factor concentrations is discussed."}
{"id": "PMID:12242", "title": "An electrophysiological study of mechanisms controlling polyp retraction in colonies of the scleractinian coral Goniopora lobata.", "content": "1. Electrical or mechanical stimulation of Goniopora lobata produces coordinated retraction of polyps in the colony. With repetitive stimulation, the response spreads in linear, radial increments which become successively smaller with each stimulus. 2. Electrical activity recorded from these colonies is interpreted as originating in a conduction system responsible for effecting the colonial retraction response. The electrical activity spreads incrementally through the colony in a similar manner to the behavioural response. 3. Various hypotheses have been proposed to account for such a spread of electrical acitvity. Of these, only interneural facilitation is of appreciable importance to Goniopora. 4. Temporary termination of a pathway, by the passage of an impulse through it, was found and interpreted as being an additional and important property of the colonial conduction system.", "contents": "An electrophysiological study of mechanisms controlling polyp retraction in colonies of the scleractinian coral Goniopora lobata. 1. Electrical or mechanical stimulation of Goniopora lobata produces coordinated retraction of polyps in the colony. With repetitive stimulation, the response spreads in linear, radial increments which become successively smaller with each stimulus. 2. Electrical activity recorded from these colonies is interpreted as originating in a conduction system responsible for effecting the colonial retraction response. The electrical activity spreads incrementally through the colony in a similar manner to the behavioural response. 3. Various hypotheses have been proposed to account for such a spread of electrical acitvity. Of these, only interneural facilitation is of appreciable importance to Goniopora. 4. Temporary termination of a pathway, by the passage of an impulse through it, was found and interpreted as being an additional and important property of the colonial conduction system."}
{"id": "PMID:12243", "title": "Possible involvement of monoamines in the release of adipokinetic hormone in the locust Schistocerca gregaria.", "content": "1. The adipokinetic hormone release, which can be induced by anticholinesterases, is reduced by depleting the content of monoamines in the nervous system. 2. The participation of monoamines in the pathway of release of adipokinetic hormone is studied in vivo and in vitro. 3. A possible mechanism for anticholinesterase-induced release of this hormone involving cholinergic and aminergic transmission is postulated.", "contents": "Possible involvement of monoamines in the release of adipokinetic hormone in the locust Schistocerca gregaria. 1. The adipokinetic hormone release, which can be induced by anticholinesterases, is reduced by depleting the content of monoamines in the nervous system. 2. The participation of monoamines in the pathway of release of adipokinetic hormone is studied in vivo and in vitro. 3. A possible mechanism for anticholinesterase-induced release of this hormone involving cholinergic and aminergic transmission is postulated."}
{"id": "PMID:12244", "title": "Oxygen dissociation curves of the blood of larval and adult lampreys (Lampetra fluviatilis).", "content": "1. An electrolytic method was used to plot the oxygen dissociation curves of whole blood from both the larva and adult of the lamprey Lampetra fluviatilis at a temperature of 10 degrees C and over a pH range of 6-5-8-1. 2. Larval blood has a far higher affinity for oxygen than that of adults, the respective calculated P50's at a pH of 7-75 being 1-9 and 10-7 mmHg. 3. The high affinity of larval blood is of use to a relatively sedentary animal living in burrows, and the increased oxygen delivery pressure brought about by the shift of the curve to the right in the adult is of advantage to an animal exhibiting greater activity. 4. The n value obtained from the Hill plots increased with increasing saturation and were lower in larvae than adults at the same level of blood saturation. 5. The Bohr effect in larvae at 10 degrees C over the pH range 6-5-8-1 was --0-25, a value which did not differ significantly from the -0-22 found in adults.", "contents": "Oxygen dissociation curves of the blood of larval and adult lampreys (Lampetra fluviatilis). 1. An electrolytic method was used to plot the oxygen dissociation curves of whole blood from both the larva and adult of the lamprey Lampetra fluviatilis at a temperature of 10 degrees C and over a pH range of 6-5-8-1. 2. Larval blood has a far higher affinity for oxygen than that of adults, the respective calculated P50's at a pH of 7-75 being 1-9 and 10-7 mmHg. 3. The high affinity of larval blood is of use to a relatively sedentary animal living in burrows, and the increased oxygen delivery pressure brought about by the shift of the curve to the right in the adult is of advantage to an animal exhibiting greater activity. 4. The n value obtained from the Hill plots increased with increasing saturation and were lower in larvae than adults at the same level of blood saturation. 5. The Bohr effect in larvae at 10 degrees C over the pH range 6-5-8-1 was --0-25, a value which did not differ significantly from the -0-22 found in adults."}
{"id": "PMID:12245", "title": "Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors.", "content": "Serum or urine from normal adult Lewis rats can be shown to contain detectable amounts of idiotypic, antigen-binding receptors with specificity for the major histocompatibility complex locus antigens of the rat, the Ag-B locus antigens. Such purified naturally occurring receptor molecules, be they of T- or B-lymphocyte origin, can be used in a polymerized form to provoke the production of auto-anti-idiotypic antibodies when injected back into normal Lewis rats. As a consequence of this autoimmunity, lymphocytes of these Lewis rats can be shown to be depleted of cells carrying the relevant idiotypic receptors signifying reactivity against a given Ag-B locus-determined antigen(s). This specific lack of idiotypic lymphocytes is manifested as a selective loss of reactivity against the relevant Ag-B-incompatible antigens as measured by graft versus host or MLC reactions. Furthermore, autoimmune Lewis rats display specific transplantation tolerance against the skin grafts from the relevant strain, as demonstrated by specific prolongation of graft survival. A further indication of the specific tolerence state of these rats comes from the highly reduced ability to produce circulating antibodies against the relevant Ag-B antigens. No side effects of these autoimmunization procedures have been noted so far. It would thus seem clear that a prolonged state of specific transplantation tolerance can be achieved via autoimmunization against the individual's naturally occurring idiotypic, antigen-binding receptors.", "contents": "Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors. Serum or urine from normal adult Lewis rats can be shown to contain detectable amounts of idiotypic, antigen-binding receptors with specificity for the major histocompatibility complex locus antigens of the rat, the Ag-B locus antigens. Such purified naturally occurring receptor molecules, be they of T- or B-lymphocyte origin, can be used in a polymerized form to provoke the production of auto-anti-idiotypic antibodies when injected back into normal Lewis rats. As a consequence of this autoimmunity, lymphocytes of these Lewis rats can be shown to be depleted of cells carrying the relevant idiotypic receptors signifying reactivity against a given Ag-B locus-determined antigen(s). This specific lack of idiotypic lymphocytes is manifested as a selective loss of reactivity against the relevant Ag-B-incompatible antigens as measured by graft versus host or MLC reactions. Furthermore, autoimmune Lewis rats display specific transplantation tolerance against the skin grafts from the relevant strain, as demonstrated by specific prolongation of graft survival. A further indication of the specific tolerence state of these rats comes from the highly reduced ability to produce circulating antibodies against the relevant Ag-B antigens. No side effects of these autoimmunization procedures have been noted so far. It would thus seem clear that a prolonged state of specific transplantation tolerance can be achieved via autoimmunization against the individual's naturally occurring idiotypic, antigen-binding receptors."}
{"id": "PMID:12246", "title": "Respiratory behaviour of sea-urchin spermatozoa. I. Effect of pH and egg water on the respiratory rate.", "content": "Effects of pH and egg water on the respiration of sea-urchin spermatozoa were polarographically studied in three sea-urchins and one starfish species. Sea-urchin sperm respiration is extremely sensitive to change in the pH of the suspending medium over a wide range. In normal-sea water, the pH of the sperm suspension decreased from 8.02 to 7.62, after four to five minutes' incubation at 18 degrees C. The Respiratory Dilution Effect could be recognized in the same medium. However, when sea water was buffered with HEPES at pH 8.2, the Effect was no longer observed. The diffusate from egg water (jelly coat solution) brought about a striking increase in the respiration when added to moderately respiring spermatozoa in HEPES-sea water of pH values lower than 7.9. No inccrease in the respiration was observed when the diffusate was added to vigorously respiring spermatozoa in HEPES-sea water of pH values higher than 8.2. Sperm motility was also inhibited by acid pH, and this inhibition was reversed by the addition of the diffusate. It does not seem that there is any species-specificity among three sea-urchins and one starfish used. The role of the diffusate is discussed in relation to the penetration of spermatozoa through the jelly coat to the egg surface.", "contents": "Respiratory behaviour of sea-urchin spermatozoa. I. Effect of pH and egg water on the respiratory rate. Effects of pH and egg water on the respiration of sea-urchin spermatozoa were polarographically studied in three sea-urchins and one starfish species. Sea-urchin sperm respiration is extremely sensitive to change in the pH of the suspending medium over a wide range. In normal-sea water, the pH of the sperm suspension decreased from 8.02 to 7.62, after four to five minutes' incubation at 18 degrees C. The Respiratory Dilution Effect could be recognized in the same medium. However, when sea water was buffered with HEPES at pH 8.2, the Effect was no longer observed. The diffusate from egg water (jelly coat solution) brought about a striking increase in the respiration when added to moderately respiring spermatozoa in HEPES-sea water of pH values lower than 7.9. No inccrease in the respiration was observed when the diffusate was added to vigorously respiring spermatozoa in HEPES-sea water of pH values higher than 8.2. Sperm motility was also inhibited by acid pH, and this inhibition was reversed by the addition of the diffusate. It does not seem that there is any species-specificity among three sea-urchins and one starfish used. The role of the diffusate is discussed in relation to the penetration of spermatozoa through the jelly coat to the egg surface."}
{"id": "PMID:12247", "title": "Respiratory behaviour of sea-urchin spermatozoa. II. Sperm-activating substance obtained from jelly coat of sea-urchin eggs.", "content": "A sperm-activating substance (SAS) was obtained from the jelly coat of sea-urchin ova and its chemical properties were investigated in three sea-urchin species. The SAS was partially purified from the jelly coat of Pseudocentrotus eggs through several steps of purification by procedures consisting of charcoal adsorption, ion-exchange chromatography on DEAE-Sephadex A-25 column, and gel-filtration on Sephadex G-15 columns. The partially purified SAS was found to contain a ninhydrin-positive material and is inactivated by pronase digestion. The molecular weight of SAS was estimated as about 630 by gel-filtration through Sephadex G-25 and the isoelectric-point of SAS is located at about pH 5.3 by isoelectrofocusing method. The SAS is non-volatile, alcohol-soluble, and labile in a diluted alkaline or acid solution. The origin of SAS is discussed.", "contents": "Respiratory behaviour of sea-urchin spermatozoa. II. Sperm-activating substance obtained from jelly coat of sea-urchin eggs. A sperm-activating substance (SAS) was obtained from the jelly coat of sea-urchin ova and its chemical properties were investigated in three sea-urchin species. The SAS was partially purified from the jelly coat of Pseudocentrotus eggs through several steps of purification by procedures consisting of charcoal adsorption, ion-exchange chromatography on DEAE-Sephadex A-25 column, and gel-filtration on Sephadex G-15 columns. The partially purified SAS was found to contain a ninhydrin-positive material and is inactivated by pronase digestion. The molecular weight of SAS was estimated as about 630 by gel-filtration through Sephadex G-25 and the isoelectric-point of SAS is located at about pH 5.3 by isoelectrofocusing method. The SAS is non-volatile, alcohol-soluble, and labile in a diluted alkaline or acid solution. The origin of SAS is discussed."}
{"id": "PMID:12254", "title": "Deficiency of NADPH oxidase activity in chronic granulomatous disease.", "content": "NADPH oxidase activity was examined in paired 27,000 x g granule fractions isolated from normal polymorphonuclear leukocytes from patients with chronic granulomatous disease. At 0.17 mM NADPH, the oxidase activity was not measurable in normal resting cells but was activated by phagocytosis. This activation was absent in CGD cells. At higher levels of NADPH, activity was present in cells from patients with CGD, although it was lower than normal, and no difference in activity was found between resting and phagocytizing cells. Granule fractions from phagocytizing normal cells exhibited higher than granule fractions from resting normal cells at all levels of NADPH. These results suggest that NADPH oxidase activity is defective in chronic granulomatous disease, and further that the defect is not the absence of the enzyme but rather a failure to activate it.", "contents": "Deficiency of NADPH oxidase activity in chronic granulomatous disease. NADPH oxidase activity was examined in paired 27,000 x g granule fractions isolated from normal polymorphonuclear leukocytes from patients with chronic granulomatous disease. At 0.17 mM NADPH, the oxidase activity was not measurable in normal resting cells but was activated by phagocytosis. This activation was absent in CGD cells. At higher levels of NADPH, activity was present in cells from patients with CGD, although it was lower than normal, and no difference in activity was found between resting and phagocytizing cells. Granule fractions from phagocytizing normal cells exhibited higher than granule fractions from resting normal cells at all levels of NADPH. These results suggest that NADPH oxidase activity is defective in chronic granulomatous disease, and further that the defect is not the absence of the enzyme but rather a failure to activate it."}
{"id": "PMID:12255", "title": "Development of the Timor filaria in Aedes togoi: preliminary observations.", "content": "Developmental stages of the Timor filaria recovered from experimentally infected Aedes togoi mosquitoes are described. Mosquitoes were dissected and examined for larvae beginning 1 1/2 days and continuing daily for 9 days after they had fed on a carrier on the island of Flores, Indonesia. Timor microfilariae develop rapidly to third-stage larvae within the thoracic muscles of A. togoi: the first molt occurs at 3 1/2 days, the second molt as early as 5 1/2 days, and infective forms are found at 6 1/2 to 7 1/2 days postfeeding. These larvae were compared with similar stages of subperiodic Brugia malayi recovered from A. togoi fed on an infected jird (Meriones unguiculatus) and the features distinguishing larvae of the Timor filaria from those of B. malayi are restricted to the tails of the first-stage forms. The terminal and subterminal nuclei of the Timor larva are generally smaller than those of B. malayi, and there is little if any bulge of the cuticle around them. A constriction of the tail between these nuclei is subtle or absent. The findings of this study support the view that the Timor filaria is a member of the Brugia complex.", "contents": "Development of the Timor filaria in Aedes togoi: preliminary observations. Developmental stages of the Timor filaria recovered from experimentally infected Aedes togoi mosquitoes are described. Mosquitoes were dissected and examined for larvae beginning 1 1/2 days and continuing daily for 9 days after they had fed on a carrier on the island of Flores, Indonesia. Timor microfilariae develop rapidly to third-stage larvae within the thoracic muscles of A. togoi: the first molt occurs at 3 1/2 days, the second molt as early as 5 1/2 days, and infective forms are found at 6 1/2 to 7 1/2 days postfeeding. These larvae were compared with similar stages of subperiodic Brugia malayi recovered from A. togoi fed on an infected jird (Meriones unguiculatus) and the features distinguishing larvae of the Timor filaria from those of B. malayi are restricted to the tails of the first-stage forms. The terminal and subterminal nuclei of the Timor larva are generally smaller than those of B. malayi, and there is little if any bulge of the cuticle around them. A constriction of the tail between these nuclei is subtle or absent. The findings of this study support the view that the Timor filaria is a member of the Brugia complex."}
{"id": "PMID:12256", "title": "Acetylcholine synthesis in sympathetic human neuroblastoma.", "content": "The synthesis of acetylcholine, as well as catecholamines, was studied by assaying the activities of choline acetyltransferase (ChA) and tyrosine hydroxylase (TH) in the tumor tissues and the culture cells of human neuroblastoma. In the majority of 20 neuroblastomas of sympathetic origin, both ChA and TH activities were detected at a significantly high level. In the culture cells of five cell lines of human neuroblastoma, ChA activity was high, but TH was negative in four of the lines. However, it was observed that these enzyme activities changed significantly while in the long-term culture. ChA assay is a useful diagnostic test for neuroblastomas that synthesize acetylcholine. Future studies of neuroblastoma should consider cholinergic activity.", "contents": "Acetylcholine synthesis in sympathetic human neuroblastoma. The synthesis of acetylcholine, as well as catecholamines, was studied by assaying the activities of choline acetyltransferase (ChA) and tyrosine hydroxylase (TH) in the tumor tissues and the culture cells of human neuroblastoma. In the majority of 20 neuroblastomas of sympathetic origin, both ChA and TH activities were detected at a significantly high level. In the culture cells of five cell lines of human neuroblastoma, ChA activity was high, but TH was negative in four of the lines. However, it was observed that these enzyme activities changed significantly while in the long-term culture. ChA assay is a useful diagnostic test for neuroblastomas that synthesize acetylcholine. Future studies of neuroblastoma should consider cholinergic activity."}
{"id": "PMID:12258", "title": "Some biological and pharmacological properties of inflammatory exudates.", "content": "Inflammatory exudates were obtained from polyester sponges which had been implanted subcutaneously in rats four days previously. This material was found to be anti-inflammatory when injected into other rats in which carrageenan pleurisy had been induced. At a dose of 600 mg kg-1 exudate inhibited the formation of pleural effusion, emigration of both neutrophils and mononuclear cells and the accumulation of beta-glucuronidase and lactic dehydrogenase. The same dose of sponge exudate did not however inhibit the increased vascular permeability induced in the rat skin or rat foot following injection of 5-hydroxytryptamine, histamine, prostaglandin E1, or bradykinin. Furthermore sponge exudate did not reduce the haemolytic complement titre of rat serum either in vivo or in vitro. The possible mechanism of anti-inflammatory action of exudate is discussed.", "contents": "Some biological and pharmacological properties of inflammatory exudates. Inflammatory exudates were obtained from polyester sponges which had been implanted subcutaneously in rats four days previously. This material was found to be anti-inflammatory when injected into other rats in which carrageenan pleurisy had been induced. At a dose of 600 mg kg-1 exudate inhibited the formation of pleural effusion, emigration of both neutrophils and mononuclear cells and the accumulation of beta-glucuronidase and lactic dehydrogenase. The same dose of sponge exudate did not however inhibit the increased vascular permeability induced in the rat skin or rat foot following injection of 5-hydroxytryptamine, histamine, prostaglandin E1, or bradykinin. Furthermore sponge exudate did not reduce the haemolytic complement titre of rat serum either in vivo or in vitro. The possible mechanism of anti-inflammatory action of exudate is discussed."}
{"id": "PMID:12259", "title": "The role of copper in preventing gastrointestinal damage by acidic anti-inflammatory drugs.", "content": "The ability of several non-steroidal acidic anti-inflammatory drugs to cause ulceration when given as copper complexes has been examined. The damage caused by clopirac, niflumic acid and aspirin was virtually abolished when they were given as copper complexes whereas the damage caused by indomethacin, ketoprofen and (+)-naproxen was unaltered. The lack of ulceration with three of these preparations appeared to be correlated with a much reduced ability to inhibit prostaglandin synthesis as determined using an in vitro enzyme system.", "contents": "The role of copper in preventing gastrointestinal damage by acidic anti-inflammatory drugs. The ability of several non-steroidal acidic anti-inflammatory drugs to cause ulceration when given as copper complexes has been examined. The damage caused by clopirac, niflumic acid and aspirin was virtually abolished when they were given as copper complexes whereas the damage caused by indomethacin, ketoprofen and (+)-naproxen was unaltered. The lack of ulceration with three of these preparations appeared to be correlated with a much reduced ability to inhibit prostaglandin synthesis as determined using an in vitro enzyme system."}
{"id": "PMID:12260", "title": "Methods for study of fluphenazine kinetics in man.", "content": "Fluphenazine and its principal metabolites, fluphenazine sulphoxide, and 7-hydroxyfluphenazine were identified and quantified in human plasma, urine and faeces following intramuscular and oral administration of 14C-fluphenazine dihydrochloride. The presence of a conjugate fraction was also noted. Unmetabolized fluphenazine was selectively extracted into n-heptane. The metabolites were separated by solvent extraction into toluene. Conjugates were hydrolysed back to fluphenazine, fluphenazne sulphoxide and 7-hydroxyfluphenazine. Fluphenazine and fluphenazine conjugates were also measured in the urine of patients receiving long term non-radioactive fluphenazine decanoate therapy. The urinary excretion rate of the conjugate fraction was systematically related to the plasma concentration, regardless of urine flow rate or pH, providing a convenient method for the assessment of fluphenazine kinetics by urinary excretion studies not involving administration of labelled drug.", "contents": "Methods for study of fluphenazine kinetics in man. Fluphenazine and its principal metabolites, fluphenazine sulphoxide, and 7-hydroxyfluphenazine were identified and quantified in human plasma, urine and faeces following intramuscular and oral administration of 14C-fluphenazine dihydrochloride. The presence of a conjugate fraction was also noted. Unmetabolized fluphenazine was selectively extracted into n-heptane. The metabolites were separated by solvent extraction into toluene. Conjugates were hydrolysed back to fluphenazine, fluphenazne sulphoxide and 7-hydroxyfluphenazine. Fluphenazine and fluphenazine conjugates were also measured in the urine of patients receiving long term non-radioactive fluphenazine decanoate therapy. The urinary excretion rate of the conjugate fraction was systematically related to the plasma concentration, regardless of urine flow rate or pH, providing a convenient method for the assessment of fluphenazine kinetics by urinary excretion studies not involving administration of labelled drug."}
{"id": "PMID:12261", "title": "Potentiation of dopaminergic transmission by phosphodiesterase inhibitors and cyclic nucleotides.", "content": "Experiments were made to determine whether cyclic AMP plays a role in transmission at identified dopaminergic synapses in the water snail Planorbis corneus. Intracellular stimulation of a specific dopamine neuron produces direct inhibitory postsynaptic potentials (ipsps) in a number of other neurons. These ipsps, which are mediated by dopamine, were potentiated by as much as 120% by caffeine, theophylline or dibutyryl cyclic AMP, although they were unaffected by cyclic AMP and prostaglandin E1. Caffeine and theophylline also potentiated the inhibitory response to dopamine, applied to the postsynaptic neurons by perfusion or iontophoresis, but the effects were generally much smaller (maximum potentiation 30%). The results provide evidence that postsynaptic cyclic AMP is involved in transmission at these synapses, but that the phosphodiesterase inhibitors may also have a presynaptic effect.", "contents": "Potentiation of dopaminergic transmission by phosphodiesterase inhibitors and cyclic nucleotides. Experiments were made to determine whether cyclic AMP plays a role in transmission at identified dopaminergic synapses in the water snail Planorbis corneus. Intracellular stimulation of a specific dopamine neuron produces direct inhibitory postsynaptic potentials (ipsps) in a number of other neurons. These ipsps, which are mediated by dopamine, were potentiated by as much as 120% by caffeine, theophylline or dibutyryl cyclic AMP, although they were unaffected by cyclic AMP and prostaglandin E1. Caffeine and theophylline also potentiated the inhibitory response to dopamine, applied to the postsynaptic neurons by perfusion or iontophoresis, but the effects were generally much smaller (maximum potentiation 30%). The results provide evidence that postsynaptic cyclic AMP is involved in transmission at these synapses, but that the phosphodiesterase inhibitors may also have a presynaptic effect."}
{"id": "PMID:12262", "title": "A simple technique for the frequent intravenous infusion of fluid without heparin into the rabbit.", "content": "A technique is described for the daily intravenous injection over 16 weeks in the rabbit. The system consists of a Teflon cannula passed down the external jugular vein with the tip in the superior vena cava. The cannula is joined at the point of entry to the jugular vein to a length of silicon rubber tubing, which is then passed subcutaneously to the forehead. The silicon tubing is terminated on a Luer needle hub, which is held in a simple Perspex plate secured subcutaneously between the rabbit's ears. The Luer hub is covered with a replaceable rubber cap through which injections may be made. With this system cannulae were maintained patent for 16 weeks by flushing once a day with Hanks' balanced salt solution, pH 7-4.", "contents": "A simple technique for the frequent intravenous infusion of fluid without heparin into the rabbit. A technique is described for the daily intravenous injection over 16 weeks in the rabbit. The system consists of a Teflon cannula passed down the external jugular vein with the tip in the superior vena cava. The cannula is joined at the point of entry to the jugular vein to a length of silicon rubber tubing, which is then passed subcutaneously to the forehead. The silicon tubing is terminated on a Luer needle hub, which is held in a simple Perspex plate secured subcutaneously between the rabbit's ears. The Luer hub is covered with a replaceable rubber cap through which injections may be made. With this system cannulae were maintained patent for 16 weeks by flushing once a day with Hanks' balanced salt solution, pH 7-4."}
{"id": "PMID:12263", "title": "Anabolic and androgenic activities, in rat, of some nandrolone and androstanolone esters.", "content": "The anabolic and androgenic activities of the formate to undecanoate esters of nandrolone and formate to valerate esters of androstanolone, after intramuscular injection, have been determined in rat. The response to a given dose was measured as cumulative weight (the area under the plot of weight of indicator organ against time). Levator anus muscle was used to assess anabolic activity, and the sum of the cumulative weight for prostate and seminal vesicles for androgenic activity. Log dose-log cumulative weights plots were parallel, and biological activities were expressed as the cumulative weight corresponding to a 2 muM dose, calculated from the regression lines. Anabolic-androgenic ratios for both series were calculated and were found to be minimum in the region of the propionate and butyrate. The anabolic-androgenic ratios of the nandrolone esters continued to increase after the minimum, as the series ascended. This method is believed to give a reliable assessment of anabolic and androgenic activities of steroid esters.", "contents": "Anabolic and androgenic activities, in rat, of some nandrolone and androstanolone esters. The anabolic and androgenic activities of the formate to undecanoate esters of nandrolone and formate to valerate esters of androstanolone, after intramuscular injection, have been determined in rat. The response to a given dose was measured as cumulative weight (the area under the plot of weight of indicator organ against time). Levator anus muscle was used to assess anabolic activity, and the sum of the cumulative weight for prostate and seminal vesicles for androgenic activity. Log dose-log cumulative weights plots were parallel, and biological activities were expressed as the cumulative weight corresponding to a 2 muM dose, calculated from the regression lines. Anabolic-androgenic ratios for both series were calculated and were found to be minimum in the region of the propionate and butyrate. The anabolic-androgenic ratios of the nandrolone esters continued to increase after the minimum, as the series ascended. This method is believed to give a reliable assessment of anabolic and androgenic activities of steroid esters."}
{"id": "PMID:12264", "title": "The adhesion of film coatings to tablet surfaces--instrumentation and preliminary evaluation.", "content": "The strength of the adhesive bond between a film coating and a tablet surface has been studied using a specially designed tensile testing apparatus. The adhesion has been taken as the force required to remove the film from unit area of the tablet surface and has been shown to be dependent on the compression pressure used to prepare the tablet and on changes in the film formulation. Although plasticizers did not show any significant effect on the adhesion of a hydroxypropyl methylcellulose film, a reduction of 45% was found on the addition of 10% w/w titanium dioxide.", "contents": "The adhesion of film coatings to tablet surfaces--instrumentation and preliminary evaluation. The strength of the adhesive bond between a film coating and a tablet surface has been studied using a specially designed tensile testing apparatus. The adhesion has been taken as the force required to remove the film from unit area of the tablet surface and has been shown to be dependent on the compression pressure used to prepare the tablet and on changes in the film formulation. Although plasticizers did not show any significant effect on the adhesion of a hydroxypropyl methylcellulose film, a reduction of 45% was found on the addition of 10% w/w titanium dioxide."}
{"id": "PMID:12265", "title": "Size analysis of metered suspension pressurized aerosols with the Quantimet 720.", "content": "A method is described for particle sizing of pressurized metered suspension aerosols by collection in a settling drum followed by microscopic evaluation of the slides with a Quantimet 720 automatic image analyser. The method gives satisfactory representation of the distribution of particles settling to the drum base, and demonstrates the excellent stability and reproducibility between and within aerosol packs for two widely used inhalation products. There is much drug deposition of somewhat finer size distribution on the wall of the drum than on the drum base. In spite of this wall loss, the method gives only slightly higher results for the weight and number mean diameters, than when both wall and base distributions are considered. The Quantimet was found to be suitable for particle sizing salbutamol used in preparing aerosol products.", "contents": "Size analysis of metered suspension pressurized aerosols with the Quantimet 720. A method is described for particle sizing of pressurized metered suspension aerosols by collection in a settling drum followed by microscopic evaluation of the slides with a Quantimet 720 automatic image analyser. The method gives satisfactory representation of the distribution of particles settling to the drum base, and demonstrates the excellent stability and reproducibility between and within aerosol packs for two widely used inhalation products. There is much drug deposition of somewhat finer size distribution on the wall of the drum than on the drum base. In spite of this wall loss, the method gives only slightly higher results for the weight and number mean diameters, than when both wall and base distributions are considered. The Quantimet was found to be suitable for particle sizing salbutamol used in preparing aerosol products."}
{"id": "PMID:12266", "title": "Size analysis of suspension inhalation aerosols by inertial separation methods.", "content": "The particle size distribution of beclomethasone dipropionate (BDP) aerosols delivered from pressurized metered dose suspension inhalers has been measured with three cascaded inertial separation instruments, the Casella Cascade Impactor, Multistage Liquid Impinger and Cascade Centripeter. Various methods for collecting the emitted aerosol before measurement have been examined. A bent glass tubular 'throat', used as a simulated oro-pharynx, collects 35-60% of the emitted dose by impingement of the wet spray cone in the throat. The aerosol passing through the throat has a similar but somewhat finer size distribution to that collected by firing directly into a large flask. The three cascaded instruments give similar results which in the Multistage Liquid Impinger also resemble those given by a salbutamol inhaler. The mass fraction (35-60%) emitted from the oral adaptor which is of a size capable of deep lung penetration ( less than 4 mum) is much higher than the fraction (10-16%) found in the lungs of dogs after inhalation of aerosol. The size distributions resemble those determined by microscopy and are expressed as aerodynamic sizes, thus showing that the particles approximate to unit density spheres. The performance of two simpler devices, Kirk's apparatus and the Harwell size selective air sampler are also assessed, the latter shows some promise for the simple evaluation of the respirable fraction of inhalation aerosols.", "contents": "Size analysis of suspension inhalation aerosols by inertial separation methods. The particle size distribution of beclomethasone dipropionate (BDP) aerosols delivered from pressurized metered dose suspension inhalers has been measured with three cascaded inertial separation instruments, the Casella Cascade Impactor, Multistage Liquid Impinger and Cascade Centripeter. Various methods for collecting the emitted aerosol before measurement have been examined. A bent glass tubular 'throat', used as a simulated oro-pharynx, collects 35-60% of the emitted dose by impingement of the wet spray cone in the throat. The aerosol passing through the throat has a similar but somewhat finer size distribution to that collected by firing directly into a large flask. The three cascaded instruments give similar results which in the Multistage Liquid Impinger also resemble those given by a salbutamol inhaler. The mass fraction (35-60%) emitted from the oral adaptor which is of a size capable of deep lung penetration ( less than 4 mum) is much higher than the fraction (10-16%) found in the lungs of dogs after inhalation of aerosol. The size distributions resemble those determined by microscopy and are expressed as aerodynamic sizes, thus showing that the particles approximate to unit density spheres. The performance of two simpler devices, Kirk's apparatus and the Harwell size selective air sampler are also assessed, the latter shows some promise for the simple evaluation of the respirable fraction of inhalation aerosols."}
{"id": "PMID:12267", "title": "An investigation into the deposition of inhalation aerosol particles as a function of air flow rate in a modified 'Kirk Lung'.", "content": "The effect of air flow rate on the deposition of inhalation aerosol particles in a modified 'Kirk Lung' has been studied. Two commercial products were used. The amount depositied in the mouthpiece and throat regions decreases with increasing flow rate. The amount in the collector rises to maximum of approximately 50%. This material represents the therapeutically available portion. Such an apparatus would be useful for routine quality control of the size distribution ratios for inhalation aerosol particles.", "contents": "An investigation into the deposition of inhalation aerosol particles as a function of air flow rate in a modified 'Kirk Lung'. The effect of air flow rate on the deposition of inhalation aerosol particles in a modified 'Kirk Lung' has been studied. Two commercial products were used. The amount depositied in the mouthpiece and throat regions decreases with increasing flow rate. The amount in the collector rises to maximum of approximately 50%. This material represents the therapeutically available portion. Such an apparatus would be useful for routine quality control of the size distribution ratios for inhalation aerosol particles."}
{"id": "PMID:12268", "title": "The in vitro dissolution of phenobarbitone sodium from ethyl cellulose microcapsules.", "content": "Microcapsules of sodium phenobarbitone, with a wall of ethyl cellulose, have been prepared. The size distribution was determined by use of standard sieves and the effect of coreWALL ratio noted. Release of the drug into an aqueous medium was studied. The release pattern was found to have similar characteristics to the release of a drug from an insoluble porous matrix.", "contents": "The in vitro dissolution of phenobarbitone sodium from ethyl cellulose microcapsules. Microcapsules of sodium phenobarbitone, with a wall of ethyl cellulose, have been prepared. The size distribution was determined by use of standard sieves and the effect of coreWALL ratio noted. Release of the drug into an aqueous medium was studied. The release pattern was found to have similar characteristics to the release of a drug from an insoluble porous matrix."}
{"id": "PMID:12269", "title": "The granulation of binary mixtures: the effects of the properties of the component powders on granules.", "content": "Sulphanilamide and citric acid individually and in various proportions with lactose, have been granulated by massing and screening. There was an optimum blend, that produced granules of maximum mean size and strength, for each binary system examined. The proportion of the components of this optimal blend was dependent on the physical properties of the second component in a mixture with lactose. Results from three systems, lactose:boric acid, lactose:sulphanilamide and lactose:citric acid indicate that although part dissolution of powder during granulation is a factor affecting granule properties, in some systems other physical properties of the second component may become dominant. It is suggested that the combined effect of cohesiveness and wettability of the powders may make the major contribution to granule strength with the sulphanilamide systems. The ultimate mean granule size produced is determined by the wettability or solubiluty of the powders, or both, in all cases examined. The great affinity of citric acid for aqueous binder solution was the dominant factor determining the properties of granules prepared from lactose:citric acid mixtures.", "contents": "The granulation of binary mixtures: the effects of the properties of the component powders on granules. Sulphanilamide and citric acid individually and in various proportions with lactose, have been granulated by massing and screening. There was an optimum blend, that produced granules of maximum mean size and strength, for each binary system examined. The proportion of the components of this optimal blend was dependent on the physical properties of the second component in a mixture with lactose. Results from three systems, lactose:boric acid, lactose:sulphanilamide and lactose:citric acid indicate that although part dissolution of powder during granulation is a factor affecting granule properties, in some systems other physical properties of the second component may become dominant. It is suggested that the combined effect of cohesiveness and wettability of the powders may make the major contribution to granule strength with the sulphanilamide systems. The ultimate mean granule size produced is determined by the wettability or solubiluty of the powders, or both, in all cases examined. The great affinity of citric acid for aqueous binder solution was the dominant factor determining the properties of granules prepared from lactose:citric acid mixtures."}
{"id": "PMID:12368", "title": "Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines.", "content": "The synthesis of (R)-(+)-4-methyl-2-(1-naphthylmethyl)imidazoline hydrochloride (2) and (S)-(-)-4-methyl-2-(1-naphthylmethyl)imidazoline hydrochloride (3) is presented. The synthesis involves the preparation of (R)-(+)- and (S)-(-)-1,2-diaminopropane dihydrochloride and then allowing the appropriate diaminopropane to react with ethyl 1-naphthyliminoacetate hydrochloride in the presence of triethylamine. The parent compound, naphazoline, is a potent alpha-adrenoreceptor agonist (-log ED50 = 7.22), whereas the methylated derivatives, 2 and 3, were moderately potent antagonists (pA2 = 5.6 and 5.8, respectively) of the alpha-adrenoreceptor. Compounds 2 and 3 also produced blockade of the response to histamine on the rabbit aorta, but at concentrations approximately 20 times higher than necessary to produce equal blockade of the alpha-adrenoreceptor.", "contents": "Stereochemical studies of adrenergic drugs. Optically active derivatives of imidazolines. The synthesis of (R)-(+)-4-methyl-2-(1-naphthylmethyl)imidazoline hydrochloride (2) and (S)-(-)-4-methyl-2-(1-naphthylmethyl)imidazoline hydrochloride (3) is presented. The synthesis involves the preparation of (R)-(+)- and (S)-(-)-1,2-diaminopropane dihydrochloride and then allowing the appropriate diaminopropane to react with ethyl 1-naphthyliminoacetate hydrochloride in the presence of triethylamine. The parent compound, naphazoline, is a potent alpha-adrenoreceptor agonist (-log ED50 = 7.22), whereas the methylated derivatives, 2 and 3, were moderately potent antagonists (pA2 = 5.6 and 5.8, respectively) of the alpha-adrenoreceptor. Compounds 2 and 3 also produced blockade of the response to histamine on the rabbit aorta, but at concentrations approximately 20 times higher than necessary to produce equal blockade of the alpha-adrenoreceptor."}
{"id": "PMID:12369", "title": "Effects of staphylococcal products on locomotion and chemotaxis of human blood neutrophils and monocytes.", "content": "The effects of staphylococcal products as chemo-attractants for human blood neutrophils and monocytes and as inhibitors of locomotion of these cells were studied with bacterial cells, culture filtrates and isoelectrically focused fractions from culture filtrates of nine strains of Staphylococcus aureus. Little direct chemotactic activity of staphylococcal products for neutrophils was observed, although a chloroform-soluble extract of the whole organisms contained such activity. The major chemotactic effect of staphylococci for neutrophils was indirect, i.e., generated when the organisms or their products were incubated with plasma, perhaps due to activation of complement. In contrast, direct chemotactic activity for monocytes was found in a large number of staphylococcal fractions. Staphylococci also produced inhibitors of locomotion of both neutrophils and monocytes. Isoelectric focusing showed more fractions inhibitory for neutrophils than for monocytes. Some of the inhibitors could be identified. Staphylococcal alpha-toxin inhibited migration of both neutrophils and monocytes. Sphingomyelinase C (beta toxin) inhibited migration of monocytes but not of neutrophils. Leucocidin-rich strains were strongly active as inhibitors of neutrophil locomotion but less so as inhibitors of monocyte locomotion.", "contents": "Effects of staphylococcal products on locomotion and chemotaxis of human blood neutrophils and monocytes. The effects of staphylococcal products as chemo-attractants for human blood neutrophils and monocytes and as inhibitors of locomotion of these cells were studied with bacterial cells, culture filtrates and isoelectrically focused fractions from culture filtrates of nine strains of Staphylococcus aureus. Little direct chemotactic activity of staphylococcal products for neutrophils was observed, although a chloroform-soluble extract of the whole organisms contained such activity. The major chemotactic effect of staphylococci for neutrophils was indirect, i.e., generated when the organisms or their products were incubated with plasma, perhaps due to activation of complement. In contrast, direct chemotactic activity for monocytes was found in a large number of staphylococcal fractions. Staphylococci also produced inhibitors of locomotion of both neutrophils and monocytes. Isoelectric focusing showed more fractions inhibitory for neutrophils than for monocytes. Some of the inhibitors could be identified. Staphylococcal alpha-toxin inhibited migration of both neutrophils and monocytes. Sphingomyelinase C (beta toxin) inhibited migration of monocytes but not of neutrophils. Leucocidin-rich strains were strongly active as inhibitors of neutrophil locomotion but less so as inhibitors of monocyte locomotion."}
{"id": "PMID:12375", "title": "Osteomyelitis following puncture wounds of the foot in children.", "content": "Review of the laboratory and clinical findings and treatment of eight patients with osteomyelitis of the foot after puncture wounds revealed that: 1) osteomyelitis after puncture wounds is a infrequent but potentially serious complication, with significant morbidity; 2) osteomyelitis is frequently preceded by inadequate primary care for simple puncture wounds, and when treatment is appropriate, osteomyelitis usually can be avoided; 3) P. aeruginosa is the most commonly recovered organism; 4) the clinical presentation is characterized by a lack of systemic toxicity, paucity of laboratory abnormalities, and evidence of a localized infection process and the patient may be asymptomatic for a few days to several months after the injury before presentation of the osteomyelitis; and 5) once the infection has become established, treatment must be aggressive, including surgical debridement.", "contents": "Osteomyelitis following puncture wounds of the foot in children. Review of the laboratory and clinical findings and treatment of eight patients with osteomyelitis of the foot after puncture wounds revealed that: 1) osteomyelitis after puncture wounds is a infrequent but potentially serious complication, with significant morbidity; 2) osteomyelitis is frequently preceded by inadequate primary care for simple puncture wounds, and when treatment is appropriate, osteomyelitis usually can be avoided; 3) P. aeruginosa is the most commonly recovered organism; 4) the clinical presentation is characterized by a lack of systemic toxicity, paucity of laboratory abnormalities, and evidence of a localized infection process and the patient may be asymptomatic for a few days to several months after the injury before presentation of the osteomyelitis; and 5) once the infection has become established, treatment must be aggressive, including surgical debridement."}
{"id": "PMID:12376", "title": "Ureteral changes in polyarteritis nodosa as seen during excretory urography.", "content": "The conventional excretory urogram may provide valuable information in the diagnosis of polyarteritis nodosa. A finding of imprints on the ureteral wall or a nodular appearance of the ureter simulating a string of pearls would seem to be pathognomonic for this disorder. Two cases with these manifestations are presented and the differential diagnosis is discussed.", "contents": "Ureteral changes in polyarteritis nodosa as seen during excretory urography. The conventional excretory urogram may provide valuable information in the diagnosis of polyarteritis nodosa. A finding of imprints on the ureteral wall or a nodular appearance of the ureter simulating a string of pearls would seem to be pathognomonic for this disorder. Two cases with these manifestations are presented and the differential diagnosis is discussed."}
{"id": "PMID:12377", "title": "The incidence of intersexuality in patients with hypospadias and cryptorchidism.", "content": "The incidence of intersexuality was determined in 45 patients with cryptorchidism and hypospadias seen between 1952 and 1975. Including patients with ambiguous genitalia the incidence was 53 per cent. When patients with ambiguous genitalia were excluded, providing a group more representative of the patient population usually seen by the urologist, a diagnosis of intersexuality was made in 27 per cent. The concomitant occurrence of hypospadias and cryptorchidism should alert the urologist to evaluate the patient for the presence of intersexuality.", "contents": "The incidence of intersexuality in patients with hypospadias and cryptorchidism. The incidence of intersexuality was determined in 45 patients with cryptorchidism and hypospadias seen between 1952 and 1975. Including patients with ambiguous genitalia the incidence was 53 per cent. When patients with ambiguous genitalia were excluded, providing a group more representative of the patient population usually seen by the urologist, a diagnosis of intersexuality was made in 27 per cent. The concomitant occurrence of hypospadias and cryptorchidism should alert the urologist to evaluate the patient for the presence of intersexuality."}
{"id": "PMID:12378", "title": "Calcium oxalate crystalluria.", "content": "Calcium oxalate crystals were obtained from urine specimens submitted to a hospital laboratory. The incidence of crystalluria was 4.2 per cent of 42 times the maximum reported incidence of urinary calculi. In our opinion the crystalluria was real and not artifactual. The crystalline structure was determined by polarized light, x-ray diffraction and electron microprobe analysis. Calcium oxalate occurs in several forms--the dihydrate as bipyramidal and dodecahedral prisms, the monohydrate as biconcave ovals, dumbbell shapes and intermediate forms.", "contents": "Calcium oxalate crystalluria. Calcium oxalate crystals were obtained from urine specimens submitted to a hospital laboratory. The incidence of crystalluria was 4.2 per cent of 42 times the maximum reported incidence of urinary calculi. In our opinion the crystalluria was real and not artifactual. The crystalline structure was determined by polarized light, x-ray diffraction and electron microprobe analysis. Calcium oxalate occurs in several forms--the dihydrate as bipyramidal and dodecahedral prisms, the monohydrate as biconcave ovals, dumbbell shapes and intermediate forms."}
{"id": "PMID:12379", "title": "Congenital megalourethra associated with prune belly syndrome.", "content": "Dilation of the penile urethra is described in a male infant with the classic triad of the prune belly syndrome. This dilated penile urethra was not accompanied by obstruction of the urethra proximal or distal to the dilation. Dilation of the penile urethra is a rare feature of the prune belly syndrome and may be part of the same developmental abnormality that affects the remainder of the urinary collecting system.", "contents": "Congenital megalourethra associated with prune belly syndrome. Dilation of the penile urethra is described in a male infant with the classic triad of the prune belly syndrome. This dilated penile urethra was not accompanied by obstruction of the urethra proximal or distal to the dilation. Dilation of the penile urethra is a rare feature of the prune belly syndrome and may be part of the same developmental abnormality that affects the remainder of the urinary collecting system."}
{"id": "PMID:12380", "title": "Chromosomal studies in cryptorchidism.", "content": "The chromosomes of undescended tests from 13 boys were analyzed. In 12 of these patients the peripheral blood chromosomes were examined and in 7 the chromosomes of normal skin cultures were examined. In addition to standard techniques the chromosomes also were analyzed by G and Q-banding methods. We were unable to detect any significant abnormalities of either chromosome number of structure in the undescended testes. Thus, our investigation failed to demonstrate a chromosomal lesions that may be responsible for maldescent of the testes. Our investigation did not reveal any changes in the chromosomes of these undescended testes that could be interpreted as indicating a potentially malignant state.", "contents": "Chromosomal studies in cryptorchidism. The chromosomes of undescended tests from 13 boys were analyzed. In 12 of these patients the peripheral blood chromosomes were examined and in 7 the chromosomes of normal skin cultures were examined. In addition to standard techniques the chromosomes also were analyzed by G and Q-banding methods. We were unable to detect any significant abnormalities of either chromosome number of structure in the undescended testes. Thus, our investigation failed to demonstrate a chromosomal lesions that may be responsible for maldescent of the testes. Our investigation did not reveal any changes in the chromosomes of these undescended testes that could be interpreted as indicating a potentially malignant state."}
{"id": "PMID:12381", "title": "The staged orchiopexy: a critical review of the literature.", "content": "During the last 20 years reports have appeared describing successful results with a 2-stage orchiopexy for patients noted to have a short testicular artery on first exploration. A critical review of these reports indicates that accurate documentation of the phenomenon of spontaneously increasing spermatic cord length following surgical manipulation does not exist. It is suggested that a scientifically accurate prospective study of the staged orchiopexy is needed.", "contents": "The staged orchiopexy: a critical review of the literature. During the last 20 years reports have appeared describing successful results with a 2-stage orchiopexy for patients noted to have a short testicular artery on first exploration. A critical review of these reports indicates that accurate documentation of the phenomenon of spontaneously increasing spermatic cord length following surgical manipulation does not exist. It is suggested that a scientifically accurate prospective study of the staged orchiopexy is needed."}
{"id": "PMID:12383", "title": "Failure to prove arenavirus infection among the small mammals from an endemic area of Korean hemorrhagic nephrosonephritis.", "content": "In the light of recent knowledge on a complex of diseases caused by a new group of viruses, arenaviruses, virological studies largely directed toward small field mammals were undertaken during 1973-1974 aiming at etiological clarification of Korean hemorrhagic nephrosonephritis (KHNN). Specimens were collected in an endemic area of KHNN located north to northeast of Seoul. Virus isolation tests with 299 urine specimens and 131 mite pools recovered from small mammals and 14 acute stage sera from typical cases yielded negative results. Complement-fixation (CF) tests failed to detect antibodies against the antigens of Congo, lymphocytic choriomeningitis (LCM), Tacaribe, and Pichinde viruses among 366 small mammal sera. In addition, CF tests of 59 of the above sera against Apoi and Lassa virus antigens were negative. The results do not support the likelihood of an arenavirus being transmitted among Korean small field mammals, the overwhelming majority of which were Apodemus agrarius. A hypothesis that KHNN is caused by a virus of small field mammal origin was not proved within the technical limit of relatively unsophisticated methods employed herein.", "contents": "Failure to prove arenavirus infection among the small mammals from an endemic area of Korean hemorrhagic nephrosonephritis. In the light of recent knowledge on a complex of diseases caused by a new group of viruses, arenaviruses, virological studies largely directed toward small field mammals were undertaken during 1973-1974 aiming at etiological clarification of Korean hemorrhagic nephrosonephritis (KHNN). Specimens were collected in an endemic area of KHNN located north to northeast of Seoul. Virus isolation tests with 299 urine specimens and 131 mite pools recovered from small mammals and 14 acute stage sera from typical cases yielded negative results. Complement-fixation (CF) tests failed to detect antibodies against the antigens of Congo, lymphocytic choriomeningitis (LCM), Tacaribe, and Pichinde viruses among 366 small mammal sera. In addition, CF tests of 59 of the above sera against Apoi and Lassa virus antigens were negative. The results do not support the likelihood of an arenavirus being transmitted among Korean small field mammals, the overwhelming majority of which were Apodemus agrarius. A hypothesis that KHNN is caused by a virus of small field mammal origin was not proved within the technical limit of relatively unsophisticated methods employed herein."}
{"id": "PMID:12387", "title": "Effects of benzodiazepines and pentobarbital on the evoked potentials in the cat brain.", "content": "The sites of action of benzodiazepines, diazepam and ID-540 [7-chloro-5-(o-fluorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) on the central nervous system were examined and compared with those of pentobarbital using evoked potentials recorded on the limbic system and hypothalamus in the cat brain. Benzodiazepines affected the various neuronal connections of the intra-limbic, limbic-hypothalamic and midbrain-limbic systems; especially the amygdala (AMYG)-, ventromedial hypothalamus (VMH)- and central gray matter (SGC)-hippocampal (HIPP) evoked potentials were attenuated, whereas the AMYG-VMH, VMH-AMYG and the septum (SP)-VMH evoked potentials were facilitated. Pentobarbital selectively attenuated the SGC-, VMH- and AMYG-HIPP evoked potentials, or facilitated the VMH-AMYG and the SP-HIPP evoked potentials. Both benzodiazepines and pentobarbital affected three afferent hippocampal neuronal connections, areas of the reticulo-hypothalamic systems regulating hippocampal activity, while only benzodiazepines affected the neuronal influence of the amygdaloid and septal areas on the hypothalamus.", "contents": "Effects of benzodiazepines and pentobarbital on the evoked potentials in the cat brain. The sites of action of benzodiazepines, diazepam and ID-540 [7-chloro-5-(o-fluorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) on the central nervous system were examined and compared with those of pentobarbital using evoked potentials recorded on the limbic system and hypothalamus in the cat brain. Benzodiazepines affected the various neuronal connections of the intra-limbic, limbic-hypothalamic and midbrain-limbic systems; especially the amygdala (AMYG)-, ventromedial hypothalamus (VMH)- and central gray matter (SGC)-hippocampal (HIPP) evoked potentials were attenuated, whereas the AMYG-VMH, VMH-AMYG and the septum (SP)-VMH evoked potentials were facilitated. Pentobarbital selectively attenuated the SGC-, VMH- and AMYG-HIPP evoked potentials, or facilitated the VMH-AMYG and the SP-HIPP evoked potentials. Both benzodiazepines and pentobarbital affected three afferent hippocampal neuronal connections, areas of the reticulo-hypothalamic systems regulating hippocampal activity, while only benzodiazepines affected the neuronal influence of the amygdaloid and septal areas on the hypothalamus."}
{"id": "PMID:12388", "title": "Effects of L-glutamine of acetylsalicylic acid or taurocholic acid-induced gastric lesions and secretory changes in pylorus-ligated rats under normal or stress conditions.", "content": "An oral dosing of either acetylsalicylic acid (ASA) or taurocholic acid (TCA) to pylorus-ligated rats subjected to water-immersion stress produced severe damage to the gastric musoca in contrast to the irritation observed in non-stressed ones. The irritative activity of ASA or TCA on gastric mucosa under stress was dose-dependent. Stress itself (23 degrees C, 7 hr) did not induce any appreciable changes in gastric mucosa under stress wasic mucosa of rats. L-glutamine, given together with SAS or TCA, significantly prevented the potentiated development of SAS- or TCA-induced gastric lesions in stressed rats. L-glutamine also prevented in varying degrees the reduction of acid and increment of Na+ ion in gastric juice accumulated in stressed rats in response to ASA or TCA.", "contents": "Effects of L-glutamine of acetylsalicylic acid or taurocholic acid-induced gastric lesions and secretory changes in pylorus-ligated rats under normal or stress conditions. An oral dosing of either acetylsalicylic acid (ASA) or taurocholic acid (TCA) to pylorus-ligated rats subjected to water-immersion stress produced severe damage to the gastric musoca in contrast to the irritation observed in non-stressed ones. The irritative activity of ASA or TCA on gastric mucosa under stress was dose-dependent. Stress itself (23 degrees C, 7 hr) did not induce any appreciable changes in gastric mucosa under stress wasic mucosa of rats. L-glutamine, given together with SAS or TCA, significantly prevented the potentiated development of SAS- or TCA-induced gastric lesions in stressed rats. L-glutamine also prevented in varying degrees the reduction of acid and increment of Na+ ion in gastric juice accumulated in stressed rats in response to ASA or TCA."}
{"id": "PMID:12389", "title": "Studies on monoamine oxidase. XVIII. Enzymic properties of placental monoamine oxidase.", "content": "Enzymic properties of partially purified monoamine oxidase (MAO) from human placenta were studied with tyramine, serotonin and benzylamine as substrates. The highest activity was obtained with serotonin and almost no activity was observed with benzylamine. These results are similar to those obtained with rat placental MAO, but different from those with rabbit placental MAO. The Km values for serotonin and tyramine were found to be 0.21 mM and 0.23 mM, respectively and the pH optimum was 8.1 with either substrate. The thermal inactivation curves of this enzyme with the two substrates were identical. The pI curves for inhibition of MAO activity by harmine, pargyline and iproniazid were similar and almost the same pI 50 values for the respective inhibitors were obtained with the two substrates. MAO in human placenta differs from that in other organs, such as liver, brain and plasma from the standpoint of the substrate specificity and the inhibitor sensitivity. The possibility that human placenta contains a single form of MAO is discussed on the basis of the present results.", "contents": "Studies on monoamine oxidase. XVIII. Enzymic properties of placental monoamine oxidase. Enzymic properties of partially purified monoamine oxidase (MAO) from human placenta were studied with tyramine, serotonin and benzylamine as substrates. The highest activity was obtained with serotonin and almost no activity was observed with benzylamine. These results are similar to those obtained with rat placental MAO, but different from those with rabbit placental MAO. The Km values for serotonin and tyramine were found to be 0.21 mM and 0.23 mM, respectively and the pH optimum was 8.1 with either substrate. The thermal inactivation curves of this enzyme with the two substrates were identical. The pI curves for inhibition of MAO activity by harmine, pargyline and iproniazid were similar and almost the same pI 50 values for the respective inhibitors were obtained with the two substrates. MAO in human placenta differs from that in other organs, such as liver, brain and plasma from the standpoint of the substrate specificity and the inhibitor sensitivity. The possibility that human placenta contains a single form of MAO is discussed on the basis of the present results."}
{"id": "PMID:12391", "title": "Antagonizing effects of beta-adrenergic blockers on lucus coeruleus-induced inhibition of trigeminal nucleus neurons.", "content": "Effects of alpha- and beta-adrenergic blocking agents applied into the lateral ventricle were studied on the relay neuron in the rostral part of spinal trigeminal nucleus (STN) of cats. Conditioning stimulation of the locus coeruleus (LC) and sensory cortex (SC) inhibited the orthodromic spike generation in STN relay neuron without affecting the antidromic spike, as already reported, and re-confirmed herein. The LC-induced inhibition of orthodromic spike was significantly reduced by intraventricular administration of beta-blockers, MJ 1999 (5 mg) and propranolol (0.5 mg), while the SC-induced inhibition of orthodromic one was not modified by the beta-blockers. The antidromic spike in STN relay neuron per se remained unaffected by these treatments. Intraventricular administration of alpha-blockers such as phentolamine and phenoxybezamine produced no alterations of the LC- and SC-induced inhibition of orthodromic spike. As the beta-blockers produced a selective antagonism, noradrenaline originating in LC probably acts as an inhibitory transmitter on the STN relay neuron and is mediated by beta-receptor.", "contents": "Antagonizing effects of beta-adrenergic blockers on lucus coeruleus-induced inhibition of trigeminal nucleus neurons. Effects of alpha- and beta-adrenergic blocking agents applied into the lateral ventricle were studied on the relay neuron in the rostral part of spinal trigeminal nucleus (STN) of cats. Conditioning stimulation of the locus coeruleus (LC) and sensory cortex (SC) inhibited the orthodromic spike generation in STN relay neuron without affecting the antidromic spike, as already reported, and re-confirmed herein. The LC-induced inhibition of orthodromic spike was significantly reduced by intraventricular administration of beta-blockers, MJ 1999 (5 mg) and propranolol (0.5 mg), while the SC-induced inhibition of orthodromic one was not modified by the beta-blockers. The antidromic spike in STN relay neuron per se remained unaffected by these treatments. Intraventricular administration of alpha-blockers such as phentolamine and phenoxybezamine produced no alterations of the LC- and SC-induced inhibition of orthodromic spike. As the beta-blockers produced a selective antagonism, noradrenaline originating in LC probably acts as an inhibitory transmitter on the STN relay neuron and is mediated by beta-receptor."}
{"id": "PMID:12392", "title": "Reversible adrenergic alpha-receptor blocking action of 2,4'-dimethyl-3-piperidino-propiophenone (tolperisone).", "content": "The vascular action of 2,4'-dimethyl-3-piperidino-propiophenone hydrochloride (tolperisone hydrochloride), a centrally acting muscle relaxant, was investigated in pentobarbital anesthetized dogs. Tolperisone given intravenously produced a transient hypotension, tachycardia, and hyperventilation. The drug increased the femoral arterial flow, and decreased the superior mesenteric arterial flow following an initial transient increase. When injected directly into femoral and mesenteric arteries, tolperisone caused a rapid increase in both arterial flow (vasodilatation). However, femoral vessels were about 90 times as sensitive as mesenteric vessels to tolperisone. These results indicate that tolperisone shifts the blood volume from mesenteric (visceral) vessels to femoral (skeltal) ones. The femoral vasodilatation produced by i.a. tolperisone was not depressed by the pretreatment with i.a. propranolol, atropine or chlorphenylamine. Tolperisone decreased the contractile force in an isolated and cross-circulated papillary muscle. Tolperisone produced adrenaline reversal and antagonized the pressor response to noradrenaline. Moreover, femoral vasoconstriction caused by i.a. adrenaline was converted to vasodilatation and that caused by i.a. noradrenaline was depressed during an i.a. infusion of tolperisone. These results indicate that tolperisone blocks adrenergic alpha-receptors. The blocking action was rapid in onset, short-lived, and in addition, competitive.", "contents": "Reversible adrenergic alpha-receptor blocking action of 2,4'-dimethyl-3-piperidino-propiophenone (tolperisone). The vascular action of 2,4'-dimethyl-3-piperidino-propiophenone hydrochloride (tolperisone hydrochloride), a centrally acting muscle relaxant, was investigated in pentobarbital anesthetized dogs. Tolperisone given intravenously produced a transient hypotension, tachycardia, and hyperventilation. The drug increased the femoral arterial flow, and decreased the superior mesenteric arterial flow following an initial transient increase. When injected directly into femoral and mesenteric arteries, tolperisone caused a rapid increase in both arterial flow (vasodilatation). However, femoral vessels were about 90 times as sensitive as mesenteric vessels to tolperisone. These results indicate that tolperisone shifts the blood volume from mesenteric (visceral) vessels to femoral (skeltal) ones. The femoral vasodilatation produced by i.a. tolperisone was not depressed by the pretreatment with i.a. propranolol, atropine or chlorphenylamine. Tolperisone decreased the contractile force in an isolated and cross-circulated papillary muscle. Tolperisone produced adrenaline reversal and antagonized the pressor response to noradrenaline. Moreover, femoral vasoconstriction caused by i.a. adrenaline was converted to vasodilatation and that caused by i.a. noradrenaline was depressed during an i.a. infusion of tolperisone. These results indicate that tolperisone blocks adrenergic alpha-receptors. The blocking action was rapid in onset, short-lived, and in addition, competitive."}
{"id": "PMID:12393", "title": "Pharmacological studies on triazine derivatives V Sedative and neuroleptic actions of 2-amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10).", "content": "Pharmacological properties of 2 amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10) were investigated in mice and rats. Chlorpromazine served as a reference compound. Tr-10 expressed in general the pharmacological profiles as neuroleptic ascertained by anti-methamphetamine activity, supression of conditioned avoidance response, taming effects, decrease in exploratory behavior and cataleptogenic activity. Among these effects, anti-methamphetamine action was most potent. Different from chlorpromazine, TR-10 showed a similar pharmacological activity pattern in the intraperitoneal and oral routes of administration as depicted from ED50/LD50 values. Although the effects relevant to neuroleptics were less potent than chlorpromazine, such were seen with TR-10 at lower doses than those causing muscle relaxation. TR-10 significantly depressed the spontaneous motor activity but showed no anti-convulsant action in mice. Hypothermic action, potentiating effects of hypnotics and alpha-adrenergic blocking action, characteristic to chlorpromazine, were very weak for TR-10. TR-10 also showed low toxicity in mice (LD50 = 820 mg/kg p.o., 465 mg/kg i.p.) compared with that of chlorpromazine (LD50 = 370 mg/kg p.o., 228 mg/kg i.p.).", "contents": "Pharmacological studies on triazine derivatives V Sedative and neuroleptic actions of 2-amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10). Pharmacological properties of 2 amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10) were investigated in mice and rats. Chlorpromazine served as a reference compound. Tr-10 expressed in general the pharmacological profiles as neuroleptic ascertained by anti-methamphetamine activity, supression of conditioned avoidance response, taming effects, decrease in exploratory behavior and cataleptogenic activity. Among these effects, anti-methamphetamine action was most potent. Different from chlorpromazine, TR-10 showed a similar pharmacological activity pattern in the intraperitoneal and oral routes of administration as depicted from ED50/LD50 values. Although the effects relevant to neuroleptics were less potent than chlorpromazine, such were seen with TR-10 at lower doses than those causing muscle relaxation. TR-10 significantly depressed the spontaneous motor activity but showed no anti-convulsant action in mice. Hypothermic action, potentiating effects of hypnotics and alpha-adrenergic blocking action, characteristic to chlorpromazine, were very weak for TR-10. TR-10 also showed low toxicity in mice (LD50 = 820 mg/kg p.o., 465 mg/kg i.p.) compared with that of chlorpromazine (LD50 = 370 mg/kg p.o., 228 mg/kg i.p.)."}
{"id": "PMID:12394", "title": "Effects of narcotic analgesics on serotonin metabolism in brain of rats and mice.", "content": "The effects of narcotic analgesics on the brain 5-hydroxytryptamine (5-Ht) and 5-hydroxyindoleacetic acid (5-HIAA) levels of rats and mice were investigated in relation to our preceding data on the effect of humoral modulatorents. The results suggest that morphine accelerates the release of brain 5-HT both in rats and mice, and that neither methadone nor pethidine alters the brain 5-HT and 5-HIAA levels in rats. The morphine-induced increase in brain 5-HT turnover is likely to be involved in the morphine-induced decrease in locomotor activity and hypothermia in rats. The activity-decreasing effects of methadone or pethidine, on the other hand, are mediated by mechanisms different from those which mediate the effects of morphine. In contrast, an increase in brain 5-HT turnover in mice apparently does not play an important role on activity-increasing effects of morphine but rather participates in other pharmacological effects of morphine.", "contents": "Effects of narcotic analgesics on serotonin metabolism in brain of rats and mice. The effects of narcotic analgesics on the brain 5-hydroxytryptamine (5-Ht) and 5-hydroxyindoleacetic acid (5-HIAA) levels of rats and mice were investigated in relation to our preceding data on the effect of humoral modulatorents. The results suggest that morphine accelerates the release of brain 5-HT both in rats and mice, and that neither methadone nor pethidine alters the brain 5-HT and 5-HIAA levels in rats. The morphine-induced increase in brain 5-HT turnover is likely to be involved in the morphine-induced decrease in locomotor activity and hypothermia in rats. The activity-decreasing effects of methadone or pethidine, on the other hand, are mediated by mechanisms different from those which mediate the effects of morphine. In contrast, an increase in brain 5-HT turnover in mice apparently does not play an important role on activity-increasing effects of morphine but rather participates in other pharmacological effects of morphine."}
{"id": "PMID:12395", "title": "Selective alpha-adrenoceptor blocking actions of a new derivative of 2-halogenotheylamine: 6-(2-bromoethyl)-10,11-methylenedioxy-5,6,7,8-tetrahydrodibenz[c,e]azocine.", "content": "A new compound, 6-(2-bromoethyl)-10,11-methylenedioxy-5,6,7,8-tetrahydrodibenz [c,e] azocine (DA-VIII-MBr) was found to have a more selective alpha-adrenergic blocking action than dibenamine or phenoxybenzamine. From dose-response curves for adrenaline and 5-hydroxytryptamine (5-HT) obtained in strips of rat aorta before and after incubation with each of the three blocking agents, the fractions of receptors remaining active for adrenaline and 5-HT, respectively, were estimated. After blockade with DA-VIII-MBr the receptors for adrenaline were blocked considerably, but those for 5-HT were little affected. Dibenamine blocked the receptors to adrenaline and 5-HT almost equally. The effective dose of phenoxybenzamine for adrenaline receptors was less than one hundredth that of dibenamine or DA-VIII-MBr, but specificity for these receptors was intermediate between those of dibenamine and DA-VIII-MBr. The structure of DA-VIII-MBr is an analog of apogalanthamine and its nitrogen atom bears the 2-halogenoethylamine group in part of an eight membered ring.", "contents": "Selective alpha-adrenoceptor blocking actions of a new derivative of 2-halogenotheylamine: 6-(2-bromoethyl)-10,11-methylenedioxy-5,6,7,8-tetrahydrodibenz[c,e]azocine. A new compound, 6-(2-bromoethyl)-10,11-methylenedioxy-5,6,7,8-tetrahydrodibenz [c,e] azocine (DA-VIII-MBr) was found to have a more selective alpha-adrenergic blocking action than dibenamine or phenoxybenzamine. From dose-response curves for adrenaline and 5-hydroxytryptamine (5-HT) obtained in strips of rat aorta before and after incubation with each of the three blocking agents, the fractions of receptors remaining active for adrenaline and 5-HT, respectively, were estimated. After blockade with DA-VIII-MBr the receptors for adrenaline were blocked considerably, but those for 5-HT were little affected. Dibenamine blocked the receptors to adrenaline and 5-HT almost equally. The effective dose of phenoxybenzamine for adrenaline receptors was less than one hundredth that of dibenamine or DA-VIII-MBr, but specificity for these receptors was intermediate between those of dibenamine and DA-VIII-MBr. The structure of DA-VIII-MBr is an analog of apogalanthamine and its nitrogen atom bears the 2-halogenoethylamine group in part of an eight membered ring."}
{"id": "PMID:12403", "title": "[Arteritis of the large vessels originating at the aorta (Takayasu arteritis) in childhood (author's transl)].", "content": "A 9-month-old female child with extensive inflammatory lesions in the large arterial trunks originating at the aorta (Takayasu arteritis) was reported. Severe cerebral, intestinal and coronary circulatory disturbances as well as insufficient blood supply in both arms, particularly the left arm, developed as a result of the stenoses and obliterations. Clinical course, postmortem findings and the results of EKG, EEG and carotid angiography were discussed. The onset in infancy and the very rapid progression of the disease were unusual.", "contents": "[Arteritis of the large vessels originating at the aorta (Takayasu arteritis) in childhood (author's transl)]. A 9-month-old female child with extensive inflammatory lesions in the large arterial trunks originating at the aorta (Takayasu arteritis) was reported. Severe cerebral, intestinal and coronary circulatory disturbances as well as insufficient blood supply in both arms, particularly the left arm, developed as a result of the stenoses and obliterations. Clinical course, postmortem findings and the results of EKG, EEG and carotid angiography were discussed. The onset in infancy and the very rapid progression of the disease were unusual."}
{"id": "PMID:12404", "title": "[Cyclic AMP and plasma renin activity in renal vein blood after amitryptiline, theophylline, furosemide and beta adrenergic blocking substances (author's transl)].", "content": "The influence of amitryptiline, theophylline and furosemide on the concentration of cyclic-AMP and plasma renin activity (PRA) was investigated in renal vein plasma. Additionally, the stimulating effect of furosemide on the PRA after application of the beta-adrenergic receptor antagonists propranolol and practolol and the cyclic AMP concentration in the plasma were measured. All drugs were given intravenously. After amitryptiline cyclic-AMP concentration increased about 1.5-fold compared with the basal value,PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold compared with the basal value, PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold coa increased within 7 min and no further increase was observed till the 15th min. After practolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value within 10 min. The stimulating effect of subsequently applied furosemide on PRA was not altered, but the cyclic-AMP concentration was not changed in this time by furosemide. After propranolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value. The cyclic-AMP concentration was not influenced by the following furosemide application, in agreement with the findings after practolol, however, PRA could be stimulated only in 36% of these patients under beta-receptor blockade. Our results show that changes of the concentrations of cyclic-AMP and of PRA are independent of each other. An elevated intracellular cyclic-AMP level due to the inhibition of phosphodiesterase is as a single factor unable to stimulate renin release. Our results give no evidence of a direct involvement of the adenylcyclase-system in the mechanism of renin release. The effect of propranolol and practolol on the basal value of PRA and cyclic-AMP is equal. The different influence of 10 mg propranolol and 20 mg practolol on the stimulating effect of 40 mg furosemide on the PRA can be interpreted as a dosage problem.", "contents": "[Cyclic AMP and plasma renin activity in renal vein blood after amitryptiline, theophylline, furosemide and beta adrenergic blocking substances (author's transl)]. The influence of amitryptiline, theophylline and furosemide on the concentration of cyclic-AMP and plasma renin activity (PRA) was investigated in renal vein plasma. Additionally, the stimulating effect of furosemide on the PRA after application of the beta-adrenergic receptor antagonists propranolol and practolol and the cyclic AMP concentration in the plasma were measured. All drugs were given intravenously. After amitryptiline cyclic-AMP concentration increased about 1.5-fold compared with the basal value,PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold compared with the basal value, PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold coa increased within 7 min and no further increase was observed till the 15th min. After practolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value within 10 min. The stimulating effect of subsequently applied furosemide on PRA was not altered, but the cyclic-AMP concentration was not changed in this time by furosemide. After propranolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value. The cyclic-AMP concentration was not influenced by the following furosemide application, in agreement with the findings after practolol, however, PRA could be stimulated only in 36% of these patients under beta-receptor blockade. Our results show that changes of the concentrations of cyclic-AMP and of PRA are independent of each other. An elevated intracellular cyclic-AMP level due to the inhibition of phosphodiesterase is as a single factor unable to stimulate renin release. Our results give no evidence of a direct involvement of the adenylcyclase-system in the mechanism of renin release. The effect of propranolol and practolol on the basal value of PRA and cyclic-AMP is equal. The different influence of 10 mg propranolol and 20 mg practolol on the stimulating effect of 40 mg furosemide on the PRA can be interpreted as a dosage problem."}
{"id": "PMID:12410", "title": "[The effect of surgery, performed under ischemia, on the fine structure of the hand muscles].", "content": "The ultrastructural picture of the intact and injured hand muscles has been examined by the authors during and after operations in tourniquet ischaemia of 12 patients, in connection with tendon and nerve reconstruction. Muscle specimina were taken partly in the beginning of the ischaemization, and partly at the end ot it, every 15--20 minutes, and the muscle specimina have been examined by means of electron microscope. It has been found that in the first 2 hours of ischaemia neither the intact muscles, nor those previously injured suffer demonstrable damage.", "contents": "[The effect of surgery, performed under ischemia, on the fine structure of the hand muscles]. The ultrastructural picture of the intact and injured hand muscles has been examined by the authors during and after operations in tourniquet ischaemia of 12 patients, in connection with tendon and nerve reconstruction. Muscle specimina were taken partly in the beginning of the ischaemization, and partly at the end ot it, every 15--20 minutes, and the muscle specimina have been examined by means of electron microscope. It has been found that in the first 2 hours of ischaemia neither the intact muscles, nor those previously injured suffer demonstrable damage."}
{"id": "PMID:12411", "title": "[Simultaneous occurrence of Perthes' disease, spondylolysis-spondylolisthesis and other forms of aseptic necrosis].", "content": "Cleft formation on the lumbo-sacral spine has been observed by the authors in 15% of 32 patients with Perthes' disease--in whom follow-up examination has been performed without selection. In one case Perthes' disease was concomitant with spondylolisthesis causing no complaints. In 2 cases aspetic necrosis with other localization was found. It is presumed by the authors that between Perthes' disease and the arch rupture of the vertebrae causal relationship may exist--but also simultaneous occurrence with sterile bone necrosis with other localization is to be taken into consideration.", "contents": "[Simultaneous occurrence of Perthes' disease, spondylolysis-spondylolisthesis and other forms of aseptic necrosis]. Cleft formation on the lumbo-sacral spine has been observed by the authors in 15% of 32 patients with Perthes' disease--in whom follow-up examination has been performed without selection. In one case Perthes' disease was concomitant with spondylolisthesis causing no complaints. In 2 cases aspetic necrosis with other localization was found. It is presumed by the authors that between Perthes' disease and the arch rupture of the vertebrae causal relationship may exist--but also simultaneous occurrence with sterile bone necrosis with other localization is to be taken into consideration."}
{"id": "PMID:12412", "title": "[Axillary block anesthesia in hand surgery].", "content": "In spite of the use of narcosis on a large scale local anaesthesia is necessary in the surgery on the hand. After the discussion of the possibilities and types of local anaesthesia the axillary blocking of the plexus brachialis is dealt with in detail, and on the basis of the experience gained with 150 cases the advantages of this method are evaluated.", "contents": "[Axillary block anesthesia in hand surgery]. In spite of the use of narcosis on a large scale local anaesthesia is necessary in the surgery on the hand. After the discussion of the possibilities and types of local anaesthesia the axillary blocking of the plexus brachialis is dealt with in detail, and on the basis of the experience gained with 150 cases the advantages of this method are evaluated."}
{"id": "PMID:12408", "title": "Thermodynamic parameters for the intramolecular disordered-to-beta transition of poly(L-tyrosine) in aqueous solution.", "content": "We have examined the disordered-to-beat transition of two samples of high molecular wieght poly(L-tyrosine), a polypeptide with an ionizing side chain, by potentiometric titration of solutions of this polymer in aqueous buffer. The degree of ionization was determined spectrophotometrically from the absorption of the tyrosinate anion at 293.5 nm. By using polymer solutions of high dilution the region of the conformational transition was separated from that of aggregation. As a consequence it was possible to obtain titration data for the intramolecular transition which we believe are free of interference from aggregation. For this transition we found that deltaHO=-1330 cal/mol of residue. The two samples gave values of -3.42+/-0.14 and -3.85+/-0.10 u for the change in entropy. Possible artifactual origins for this distinction have been examined and may be dicounted. Rather, it probably reflects a difference in the beta structures formed which depends on molecular weight.", "contents": "Thermodynamic parameters for the intramolecular disordered-to-beta transition of poly(L-tyrosine) in aqueous solution. We have examined the disordered-to-beat transition of two samples of high molecular wieght poly(L-tyrosine), a polypeptide with an ionizing side chain, by potentiometric titration of solutions of this polymer in aqueous buffer. The degree of ionization was determined spectrophotometrically from the absorption of the tyrosinate anion at 293.5 nm. By using polymer solutions of high dilution the region of the conformational transition was separated from that of aggregation. As a consequence it was possible to obtain titration data for the intramolecular transition which we believe are free of interference from aggregation. For this transition we found that deltaHO=-1330 cal/mol of residue. The two samples gave values of -3.42+/-0.14 and -3.85+/-0.10 u for the change in entropy. Possible artifactual origins for this distinction have been examined and may be dicounted. Rather, it probably reflects a difference in the beta structures formed which depends on molecular weight."}
{"id": "PMID:12413", "title": "[Substitution of skull defects with methyl acrylate].", "content": "On the basis of the data of the literature and their own experiences the theoretical and pratical problems of cranioplasty are dealt with by the authors. The indications of the cranioplasty and the various materials employed are discussed. In the author's opinion, the metacrylate polymerizating to heat has been found the most practical. The use of the metacrylate implant, the modelling and the preparation of the implant, as well as a new method worked out by the authors are discussed. The operative technique, the results and the possible complications are dealt with. Also the authors' new method in order to prevent the infection from the nasal cavity is described.", "contents": "[Substitution of skull defects with methyl acrylate]. On the basis of the data of the literature and their own experiences the theoretical and pratical problems of cranioplasty are dealt with by the authors. The indications of the cranioplasty and the various materials employed are discussed. In the author's opinion, the metacrylate polymerizating to heat has been found the most practical. The use of the metacrylate implant, the modelling and the preparation of the implant, as well as a new method worked out by the authors are discussed. The operative technique, the results and the possible complications are dealt with. Also the authors' new method in order to prevent the infection from the nasal cavity is described."}
{"id": "PMID:12415", "title": "[Collagen synthesis, studied by sub microscopic methods in beta-propiolactone and in tendon homografts, preserved by gamma irradiation].", "content": "In dog experiments homologous tendos conserved in beta-propiolacton and by means of gamma-radiation have been transplanted by the authors. After the 1st, 3rd and 8th post-operative week various regions of the graft and the recipient tendon stump have been examined by means of light--, polarisation microscopic and electron microscopic method. The examinations have unanimously shown that the tendon grafts conserved in beta-propiolacton are reorganized quickly, within 8 weeks nearly completely besides hardly visible inflammatory reaction. In the meantime, the originally collagen fibrous framework is decomposed and on it a new collagen fibrous structure develops, and thus a new tendon--capable to function--is formed. On the other hand, the reorganization of the grafts conserved with gamma-radiation is protracted or it fails to occur, and cicatrization is observed. Some problems of the modern tissue preservation, the collagen synthesis occurring in the active fibroblasts, the secretion of the collagen precursory substance into the extracellulary space, as well as the formation, the structure and the constitution of the newly synthesized collagen fibres--forming the transplant--are discussed by the authors. The obtained results are demonstrated in light-, polarization microscopic and electron microscopic pictures.", "contents": "[Collagen synthesis, studied by sub microscopic methods in beta-propiolactone and in tendon homografts, preserved by gamma irradiation]. In dog experiments homologous tendos conserved in beta-propiolacton and by means of gamma-radiation have been transplanted by the authors. After the 1st, 3rd and 8th post-operative week various regions of the graft and the recipient tendon stump have been examined by means of light--, polarisation microscopic and electron microscopic method. The examinations have unanimously shown that the tendon grafts conserved in beta-propiolacton are reorganized quickly, within 8 weeks nearly completely besides hardly visible inflammatory reaction. In the meantime, the originally collagen fibrous framework is decomposed and on it a new collagen fibrous structure develops, and thus a new tendon--capable to function--is formed. On the other hand, the reorganization of the grafts conserved with gamma-radiation is protracted or it fails to occur, and cicatrization is observed. Some problems of the modern tissue preservation, the collagen synthesis occurring in the active fibroblasts, the secretion of the collagen precursory substance into the extracellulary space, as well as the formation, the structure and the constitution of the newly synthesized collagen fibres--forming the transplant--are discussed by the authors. The obtained results are demonstrated in light-, polarization microscopic and electron microscopic pictures."}
{"id": "PMID:12416", "title": "[Surgical treatment of chemical injuries].", "content": "Among nearly 2000 patients of a traumatological ward 82 patients were treated with chemical injury during 6 years. On the basis of their experiences the tissue damaging effect of the chemical substances as well as the methods of treatment are discussed by the authors. Dermoplastic operations have been performed in 28 injured patients. Two patients died--the immediate cause of death was in both patients pneumonia developed as complication of important skin defect. As first-aid abundant sponge-bath and flushing are recommended by the authors--the neutralizing drugs play a secondary role. In the case of deep injuries primary necrectomy is recommended, firstly in colliquation necrosis, as well as in the cases, in which the absorption of the poisonous substance is to be feared of.", "contents": "[Surgical treatment of chemical injuries]. Among nearly 2000 patients of a traumatological ward 82 patients were treated with chemical injury during 6 years. On the basis of their experiences the tissue damaging effect of the chemical substances as well as the methods of treatment are discussed by the authors. Dermoplastic operations have been performed in 28 injured patients. Two patients died--the immediate cause of death was in both patients pneumonia developed as complication of important skin defect. As first-aid abundant sponge-bath and flushing are recommended by the authors--the neutralizing drugs play a secondary role. In the case of deep injuries primary necrectomy is recommended, firstly in colliquation necrosis, as well as in the cases, in which the absorption of the poisonous substance is to be feared of."}
{"id": "PMID:12417", "title": "[Intramural duodenal hematoma of traumatic origin].", "content": "A rare case of the blunt abdominal injuries--forming a clinical entity--intramural duodenal haematoma is reported. The symptoms of IMDH may appear--non specifically--after a longer interval. The diagnosis is assured in the first place by careful anamnesis and on the basis of the characteristic radiological signs. The treatment may be--depending on the extent of the obstruction--conservative or surgical--in the latter case mostly the evacuation of the haematoma is performed.", "contents": "[Intramural duodenal hematoma of traumatic origin]. A rare case of the blunt abdominal injuries--forming a clinical entity--intramural duodenal haematoma is reported. The symptoms of IMDH may appear--non specifically--after a longer interval. The diagnosis is assured in the first place by careful anamnesis and on the basis of the characteristic radiological signs. The treatment may be--depending on the extent of the obstruction--conservative or surgical--in the latter case mostly the evacuation of the haematoma is performed."}
{"id": "PMID:12419", "title": "[Acute traumatic infratentorial subdural hematoma].", "content": "The case of an injured man, aged 54, is reported. On the basis of the neurological symptoms, without neuro-radiological contrast examinations, in presence of negative skull osteogram, on the day of the injury suboccipital craniectomy and removal of the subdural haematoma have been performed. The diagnostical difficulties of the occipital injury are pointed out, since both the occipital and infratentorial regions are \"silent\" regions for the carotis-angiography. In the case of subdural haematoma the suboccipital decompression performed in due time may be exactly as much successful as the supratentorial decompression.", "contents": "[Acute traumatic infratentorial subdural hematoma]. The case of an injured man, aged 54, is reported. On the basis of the neurological symptoms, without neuro-radiological contrast examinations, in presence of negative skull osteogram, on the day of the injury suboccipital craniectomy and removal of the subdural haematoma have been performed. The diagnostical difficulties of the occipital injury are pointed out, since both the occipital and infratentorial regions are \"silent\" regions for the carotis-angiography. In the case of subdural haematoma the suboccipital decompression performed in due time may be exactly as much successful as the supratentorial decompression."}
{"id": "PMID:12420", "title": "[Mistakes, errors and their prevention in the medical expertise about accidental injuries].", "content": "It may be stated that in the examination of the individuals who had suffered an accident, as well as in the assessment of the subsequent consequences--for whatever authority (social assurance, court of justice, State Insurance Company) the medical opinion is given--various errors may be committed, which may direct the claim for indemnity in a faulty way and may endanger also the medical competence of the expert opinion. The medical, social, legal and economical relationships of these errors have repeatedly been pointed out by the authors. Neither the patient nor the community may suffer a loss or injury merely by the reason that the medical expert's skill was defective regarding the medical expert's work. The aim of the authors' paper is to through a flash of light on these errors and mistakes and possibly to improve the work of the medical experts in these special fields.", "contents": "[Mistakes, errors and their prevention in the medical expertise about accidental injuries]. It may be stated that in the examination of the individuals who had suffered an accident, as well as in the assessment of the subsequent consequences--for whatever authority (social assurance, court of justice, State Insurance Company) the medical opinion is given--various errors may be committed, which may direct the claim for indemnity in a faulty way and may endanger also the medical competence of the expert opinion. The medical, social, legal and economical relationships of these errors have repeatedly been pointed out by the authors. Neither the patient nor the community may suffer a loss or injury merely by the reason that the medical expert's skill was defective regarding the medical expert's work. The aim of the authors' paper is to through a flash of light on these errors and mistakes and possibly to improve the work of the medical experts in these special fields."}
{"id": "PMID:12423", "title": "Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in the mes- and diencephalon.", "content": "The localization and distribution of tyrosine hydroxylase (TH), the first enzyme in the catecholamine synthesis, in the mes- and diencephalon has been studied with the indirect immunofluorescence technique of Coons and collaborators. Principally, TH was present in neuron systems with a distribution similar to known dopamine, noradrenaline and adrenaline systems. The present data, taken together with published and some unpublished results, indicate that all parts of most central dopamine neurons, i.e. cell body, dendrites, axon and nerve terminals, appear strongly fluorescent. The adrenaline neurons also appeared strongly fluorescent, except for their axons, which only exhibited a weak fluorescence. Only cell bodies of noradrenaline neurons were strongly fluorescent, whereas the nerve terminals and axons showed a weak or moderate fluorescence intensity. The fine noradrenaline nerve terminals in some areas, such as the thalamus, were invisible or, under favourable conditions, weakly fluorescent. Therefore, in the present study we are mainly dealing with the dopamine neurons of the upper brain stem. Our results demonstrate a widespread occurrence of TH-positive neuron systems in the mes- and diencephalon. The different mesencephalic dopamine systems and their ascending projections were visualized. Numerous TH-positive cell bodies were present along the ventricle system extending from the aqueductus cerebri to the most cranial periventricular parts of the third ventricle. The caudal part of these neurons, consisting of very small cell bodies, belong to the dorsal periventricular system described by Lindvall and Bj\u00f6rklund. Several TH-positive cell bodies were also observed in the inferior collicle of young animals. In the superficial layers of the inferior collicles TH positive nerve terminals were seen. At the hypothalamic level the A11 to A14 cell groups as well as some additonal cell bodies and extensive nerve terminal plexuses appeared strongly fluorescent. The differences in the intensity of the TH-related immunofluorescence between various brain regions and between various neuron systems may well reflect differences in enzyme levels between the various catacholamine systems rather than be due to the existence of different types of TH.", "contents": "Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in the mes- and diencephalon. The localization and distribution of tyrosine hydroxylase (TH), the first enzyme in the catecholamine synthesis, in the mes- and diencephalon has been studied with the indirect immunofluorescence technique of Coons and collaborators. Principally, TH was present in neuron systems with a distribution similar to known dopamine, noradrenaline and adrenaline systems. The present data, taken together with published and some unpublished results, indicate that all parts of most central dopamine neurons, i.e. cell body, dendrites, axon and nerve terminals, appear strongly fluorescent. The adrenaline neurons also appeared strongly fluorescent, except for their axons, which only exhibited a weak fluorescence. Only cell bodies of noradrenaline neurons were strongly fluorescent, whereas the nerve terminals and axons showed a weak or moderate fluorescence intensity. The fine noradrenaline nerve terminals in some areas, such as the thalamus, were invisible or, under favourable conditions, weakly fluorescent. Therefore, in the present study we are mainly dealing with the dopamine neurons of the upper brain stem. Our results demonstrate a widespread occurrence of TH-positive neuron systems in the mes- and diencephalon. The different mesencephalic dopamine systems and their ascending projections were visualized. Numerous TH-positive cell bodies were present along the ventricle system extending from the aqueductus cerebri to the most cranial periventricular parts of the third ventricle. The caudal part of these neurons, consisting of very small cell bodies, belong to the dorsal periventricular system described by Lindvall and Bj\u00f6rklund. Several TH-positive cell bodies were also observed in the inferior collicle of young animals. In the superficial layers of the inferior collicles TH positive nerve terminals were seen. At the hypothalamic level the A11 to A14 cell groups as well as some additonal cell bodies and extensive nerve terminal plexuses appeared strongly fluorescent. The differences in the intensity of the TH-related immunofluorescence between various brain regions and between various neuron systems may well reflect differences in enzyme levels between the various catacholamine systems rather than be due to the existence of different types of TH."}
{"id": "PMID:12424", "title": "A study of physicians' assistants in a rural setting.", "content": "In an effort to improve the health care in a rural county in Southern Appalachia, physicians' assistants (MEDEX) have been employed in the offices of three general practitioners over a three-year period. This program was evaluated using a before-after and experimental-control (county) design, utilizing data both from physician office contracts and a continuing survey of the populations of the experimental and control counties. Results show the following: 1) utilization (average office visits per week) increased; 2) types of care (preventive versus curative) remained stable; 3) the hospitalization rate increased continuously during the three years for those physicians using physicians' assistants; and 4) the physicians' assistant functioned more as a physician substitute than as an assistant. It is concluded that although use of physicians' assistants may increase utilization rates, they may not reduce the long-range cost of medical care through providing more preventive or ambulatory (as opposed to hospital) care.", "contents": "A study of physicians' assistants in a rural setting. In an effort to improve the health care in a rural county in Southern Appalachia, physicians' assistants (MEDEX) have been employed in the offices of three general practitioners over a three-year period. This program was evaluated using a before-after and experimental-control (county) design, utilizing data both from physician office contracts and a continuing survey of the populations of the experimental and control counties. Results show the following: 1) utilization (average office visits per week) increased; 2) types of care (preventive versus curative) remained stable; 3) the hospitalization rate increased continuously during the three years for those physicians using physicians' assistants; and 4) the physicians' assistant functioned more as a physician substitute than as an assistant. It is concluded that although use of physicians' assistants may increase utilization rates, they may not reduce the long-range cost of medical care through providing more preventive or ambulatory (as opposed to hospital) care."}
{"id": "PMID:12425", "title": "Adding a Medex to the medical mix: an evaluation.", "content": "Three classes of Medex were followed during their preceptorship training and subsequent employment to assess the impact of adding such physician assistants on 13 private practices. The data suggest that the Medex are readily incorporated into the practice, seeing a similar spectrum of patients and generally functioning as a semicolleague. Although the Medex was almost universally a contributing addition to the practice, increasing patient volume, the specific effects varied with the setting.", "contents": "Adding a Medex to the medical mix: an evaluation. Three classes of Medex were followed during their preceptorship training and subsequent employment to assess the impact of adding such physician assistants on 13 private practices. The data suggest that the Medex are readily incorporated into the practice, seeing a similar spectrum of patients and generally functioning as a semicolleague. Although the Medex was almost universally a contributing addition to the practice, increasing patient volume, the specific effects varied with the setting."}
{"id": "PMID:12448", "title": "[Alternativity of methane assimilation pathways in obligate methylotrophs].", "content": "The activity of key enzymes involved in the primary pathways of methane assimilation and enzymes of the citrate cycle was determined in various obligate methylotrophs: mesophilic, thermotolerant, and thermophilic. The bacteria are characterized by the membrane ultrastructure of the I type, high activity of hexosephosphate synthase, NAD- and NADP-specific isocitrate dehydrogenase, and the absence of alpha-ketoglutarate dehydrogenase. The bacteria also displayed the activity of key enzymes of the serine cycle, hydroxypyruvate reductase, and serineglyoxylate aminotransferase. Therefore, both the ribulose monophosphate and serine pathways are involved in methane assimilation, and the division of methanotrophs into two groups, according to their metabolism, is tentative.", "contents": "[Alternativity of methane assimilation pathways in obligate methylotrophs]. The activity of key enzymes involved in the primary pathways of methane assimilation and enzymes of the citrate cycle was determined in various obligate methylotrophs: mesophilic, thermotolerant, and thermophilic. The bacteria are characterized by the membrane ultrastructure of the I type, high activity of hexosephosphate synthase, NAD- and NADP-specific isocitrate dehydrogenase, and the absence of alpha-ketoglutarate dehydrogenase. The bacteria also displayed the activity of key enzymes of the serine cycle, hydroxypyruvate reductase, and serineglyoxylate aminotransferase. Therefore, both the ribulose monophosphate and serine pathways are involved in methane assimilation, and the division of methanotrophs into two groups, according to their metabolism, is tentative."}
{"id": "PMID:12450", "title": "[Effect of H+, OH-, Cu2+ and Ag+ on amino acid composition of Candida utilis cells in chemostat culture].", "content": "Amino acid composition was determined in the cells of Candida utilis VKM Y-1668 growing in the regime of chemostat. The growth was inhibited by pH of the medium, copper and silver ions, and glycerol deficiency as a control. Some specific differences have been found in the amino acid composition of the yeast depending on the nature of the inhibitor.", "contents": "[Effect of H+, OH-, Cu2+ and Ag+ on amino acid composition of Candida utilis cells in chemostat culture]. Amino acid composition was determined in the cells of Candida utilis VKM Y-1668 growing in the regime of chemostat. The growth was inhibited by pH of the medium, copper and silver ions, and glycerol deficiency as a control. Some specific differences have been found in the amino acid composition of the yeast depending on the nature of the inhibitor."}
{"id": "PMID:12452", "title": "[Biosynthesis of chitinase by Achromobacter liquefaciens].", "content": "Bacterial cultures under study synthesize exocellular chitinase on a medium containing chitin or demineralized crab shells as a source of carbon and nitrogen. Conditions for biosynthesis of chitinase by the cells of Achromobacter liquefaciens 301a were investigated under periodic and continuous conditions of cultivation. The preparation of chitinase isolated from the cultural broth of A. liquefaciens 301a hydrolysed colloid and native chitin at the optimum pH 6.5 and temperature 40degreesC. The terminal products of the reaction are chitobiose and N-acetylglucosamine.", "contents": "[Biosynthesis of chitinase by Achromobacter liquefaciens]. Bacterial cultures under study synthesize exocellular chitinase on a medium containing chitin or demineralized crab shells as a source of carbon and nitrogen. Conditions for biosynthesis of chitinase by the cells of Achromobacter liquefaciens 301a were investigated under periodic and continuous conditions of cultivation. The preparation of chitinase isolated from the cultural broth of A. liquefaciens 301a hydrolysed colloid and native chitin at the optimum pH 6.5 and temperature 40degreesC. The terminal products of the reaction are chitobiose and N-acetylglucosamine."}
{"id": "PMID:12457", "title": "The physician's assistant. A controversial topic at home and abroad.", "content": "Non-physician primary care providers (physicians' assistants) have existed in under-developed or emerging nations, in various forms, for many years. It is only recently, however, that this concept has been introduced into countries with more advanced economic and medical care systems. An active and rapidly developing physician's assistant movement has been organized in the United States since the early 1960s; physician's assistants and nurse practitioners may now be found in the almost every one of the 50 United States. Recently, this kind of concept has been suggested as a possibility for improving the Australian medical care system. This article explores the history and present status of the physician's assistant/nurse practitioner movement in the American medical care scene.", "contents": "The physician's assistant. A controversial topic at home and abroad. Non-physician primary care providers (physicians' assistants) have existed in under-developed or emerging nations, in various forms, for many years. It is only recently, however, that this concept has been introduced into countries with more advanced economic and medical care systems. An active and rapidly developing physician's assistant movement has been organized in the United States since the early 1960s; physician's assistants and nurse practitioners may now be found in the almost every one of the 50 United States. Recently, this kind of concept has been suggested as a possibility for improving the Australian medical care system. This article explores the history and present status of the physician's assistant/nurse practitioner movement in the American medical care scene."}
{"id": "PMID:12453", "title": "[Cultivation conditions of the Aspergillus terricola mutant producing proteolytic enzyme].", "content": "The effect of temperature, aeration and various foam suppressors on the growth of a mutant of Aspergillus terricola H-20 and on its production of proteolytic enzymes was studied. A high level of the proteolytic activity (12-15 PU/ml) was found at 28-30 degree C in conditions of aeration with the rate of oxygen dissolution being 0.38-0.86 g of oxygen per litre per hour. Synthesis of the enzyme was inhibited by a decrease in temperature to 22-24 degree C, a surplass (1.07 g O2 per litre per hour) or insufficient (0.18 g O2 per litre per hour) content of oxygen in the medium, and by addition of animal (sperm-whale) fat as a froth breaker to the medium. The best rate of protease biosynthesis was obtained upon stepwise addition of sunflower oil to the cultural broth. The best synthetic froth breakers for biosynthesis of the proteolytic enzyme are adecanol at a concentration of 0.1-1% and polymethylsiloxane PMS-A 154 as a water emulsion at a concentration of 0.5% of the medium volume.", "contents": "[Cultivation conditions of the Aspergillus terricola mutant producing proteolytic enzyme]. The effect of temperature, aeration and various foam suppressors on the growth of a mutant of Aspergillus terricola H-20 and on its production of proteolytic enzymes was studied. A high level of the proteolytic activity (12-15 PU/ml) was found at 28-30 degree C in conditions of aeration with the rate of oxygen dissolution being 0.38-0.86 g of oxygen per litre per hour. Synthesis of the enzyme was inhibited by a decrease in temperature to 22-24 degree C, a surplass (1.07 g O2 per litre per hour) or insufficient (0.18 g O2 per litre per hour) content of oxygen in the medium, and by addition of animal (sperm-whale) fat as a froth breaker to the medium. The best rate of protease biosynthesis was obtained upon stepwise addition of sunflower oil to the cultural broth. The best synthetic froth breakers for biosynthesis of the proteolytic enzyme are adecanol at a concentration of 0.1-1% and polymethylsiloxane PMS-A 154 as a water emulsion at a concentration of 0.5% of the medium volume."}
{"id": "PMID:12449", "title": "[Effect of growth medium composition of glucoamylase and glycosyltransferase activity of Endomyces fibuliger].", "content": "Production of glucoamylase and glycosyltransferase by Endomyces fibuliger was found to depend on sources of carbon and nitrogen nutrition. Starch at a concentration above 0.5% in the medium stimulated biosynthesis of glycosyltransferase but inhibited production of glucoamylase by End. fibuliger 20-9. The rate of growth of the micro-organism increased by a factor of 3.3 with an increase of starch concentration from 0.5 to 6%. Synthesis of glycosyltransferase was repressed by glucose, lactose, sucrose and maltose. Synthesis of glucoamylase was repressed by lactose, sorbose and galactose. Synthesis of glycosyltransferase was stimulated by xylose, sorbose and galactose. Production of glucoamylase was stimulated by xylose and arabinose. Growth of the culture and synthesis of glucoamylase and maltase in the cultural broth were stimulated by an increase in the concentration of maize extract. Biosynthesis of glucoamylase and glycosyltransferase was stimulated by NH4H2PO4.", "contents": "[Effect of growth medium composition of glucoamylase and glycosyltransferase activity of Endomyces fibuliger]. Production of glucoamylase and glycosyltransferase by Endomyces fibuliger was found to depend on sources of carbon and nitrogen nutrition. Starch at a concentration above 0.5% in the medium stimulated biosynthesis of glycosyltransferase but inhibited production of glucoamylase by End. fibuliger 20-9. The rate of growth of the micro-organism increased by a factor of 3.3 with an increase of starch concentration from 0.5 to 6%. Synthesis of glycosyltransferase was repressed by glucose, lactose, sucrose and maltose. Synthesis of glucoamylase was repressed by lactose, sorbose and galactose. Synthesis of glycosyltransferase was stimulated by xylose, sorbose and galactose. Production of glucoamylase was stimulated by xylose and arabinose. Growth of the culture and synthesis of glucoamylase and maltase in the cultural broth were stimulated by an increase in the concentration of maize extract. Biosynthesis of glucoamylase and glycosyltransferase was stimulated by NH4H2PO4."}
{"id": "PMID:12451", "title": "[Isolation and properties of the fibrinolytic enzyme from the Actinomyces thermovulgaris cultural broth].", "content": "A fibrinolytic enzyme was isolated from the cultural broth of Actinomyces thermovulgaris T-54 by precipitation with ammonium sulphate to 0.8 saturation and chromatography on GE-cellulose and CM-cellulose. The enzyme is homogeneous as was confirmed by disk electrophoresis in polyacrylamide gel. Some properties of the enzyme were studied. A modification of the method is suggested to assay the fibrinolytic activity.", "contents": "[Isolation and properties of the fibrinolytic enzyme from the Actinomyces thermovulgaris cultural broth]. A fibrinolytic enzyme was isolated from the cultural broth of Actinomyces thermovulgaris T-54 by precipitation with ammonium sulphate to 0.8 saturation and chromatography on GE-cellulose and CM-cellulose. The enzyme is homogeneous as was confirmed by disk electrophoresis in polyacrylamide gel. Some properties of the enzyme were studied. A modification of the method is suggested to assay the fibrinolytic activity."}
{"id": "PMID:12456", "title": "New approaches to the causation and prevention of cancers of epithelial surfaces.", "content": "Environmental rather than genetic factors appear to be responsible for the causation of cancers involving epithelial surfaces, especially oropharyngeal cancers, cancers of the gastro-intestinal tract, cancers of the liver and gall-bladder, cancers of the cervix uteri and lung cancers. Epithelial surfaces which have mucus-bearing cells are particularly prone, because if these mucus cells are surrounded by an alkaline milieu over a prolonged period, the mucous of the epithelial cells is rendered fluid and is removed from the cells, of which it forms an integral part. This leads to proliferative changes with metaplasia, cell-atypia and a very significant increase in mitotic activity. Such changes are a prelude to carcinogenesis. In the case of many oropharyngeal cancers in Asia and Africa it is the alkaline slaked lime in the betel quid which is responsible; in the case of gastric cancers it is the reflux of the alkaline duodenal contents into the stomach; in the case of colon it is the absence of roughage, cellulose and vegetable fibres from the diet; in the case of the cervix uteri it is the frequency of coitus which gives rise to a highly alkaline seminal fluid; and in the case of cancer lung it is the alkaline cigarette smoke.", "contents": "New approaches to the causation and prevention of cancers of epithelial surfaces. Environmental rather than genetic factors appear to be responsible for the causation of cancers involving epithelial surfaces, especially oropharyngeal cancers, cancers of the gastro-intestinal tract, cancers of the liver and gall-bladder, cancers of the cervix uteri and lung cancers. Epithelial surfaces which have mucus-bearing cells are particularly prone, because if these mucus cells are surrounded by an alkaline milieu over a prolonged period, the mucous of the epithelial cells is rendered fluid and is removed from the cells, of which it forms an integral part. This leads to proliferative changes with metaplasia, cell-atypia and a very significant increase in mitotic activity. Such changes are a prelude to carcinogenesis. In the case of many oropharyngeal cancers in Asia and Africa it is the alkaline slaked lime in the betel quid which is responsible; in the case of gastric cancers it is the reflux of the alkaline duodenal contents into the stomach; in the case of colon it is the absence of roughage, cellulose and vegetable fibres from the diet; in the case of the cervix uteri it is the frequency of coitus which gives rise to a highly alkaline seminal fluid; and in the case of cancer lung it is the alkaline cigarette smoke."}
{"id": "PMID:12463", "title": "Application of halide ion nuclear magnetic resonance to bioinorganic problems.", "content": "The basis for the application of halide ion nuclear magnetic resonance to the investigation of biochemical problems is reviewed and a summary of applications is presented. Anion binding to macromolecules, low molecular weight or model compounds, metalloenzymes, and extrinsic metal interactions with macromolecules are discussed.", "contents": "Application of halide ion nuclear magnetic resonance to bioinorganic problems. The basis for the application of halide ion nuclear magnetic resonance to the investigation of biochemical problems is reviewed and a summary of applications is presented. Anion binding to macromolecules, low molecular weight or model compounds, metalloenzymes, and extrinsic metal interactions with macromolecules are discussed."}
{"id": "PMID:12464", "title": "Determination of intermediary metabolites in yeast. Critical examination of the effect of sampling conditions and recommendations for obtaining true levels.", "content": "The effect of sampling conditions on the levels of adenine nucleotides, pyridine nucleotides, glycolytic intermediates and related metabolites in yeast has been studied. A systematic examination of the conditions for harvesting has shown that it can be best accomplished by rapid filtration. Delays in the handling for removal of the medium, as is usual in the process of obtaining a number of data reported in the literature, lead to important changes in some of the metabolites examined. It is also shown that when a washing is imperative it can be carried out with a methanol-water mixture (50/50, v/v) cooled at -40 degrees without loss of intracellular concentrations of non-readily diffusible metabolites. On the basis of this experience the outline of a generally applicable procedure is presented.", "contents": "Determination of intermediary metabolites in yeast. Critical examination of the effect of sampling conditions and recommendations for obtaining true levels. The effect of sampling conditions on the levels of adenine nucleotides, pyridine nucleotides, glycolytic intermediates and related metabolites in yeast has been studied. A systematic examination of the conditions for harvesting has shown that it can be best accomplished by rapid filtration. Delays in the handling for removal of the medium, as is usual in the process of obtaining a number of data reported in the literature, lead to important changes in some of the metabolites examined. It is also shown that when a washing is imperative it can be carried out with a methanol-water mixture (50/50, v/v) cooled at -40 degrees without loss of intracellular concentrations of non-readily diffusible metabolites. On the basis of this experience the outline of a generally applicable procedure is presented."}
{"id": "PMID:12465", "title": "The extracellular metalloprotease of Serratia marcescens: I. Purification and characterization.", "content": "An extracellular protease of Serratia marcescens produced during growth on skim milk medium was isolated by ethanol precipitation. The protease was purified by salt fractionation, DEAE-cellulose ion exchange chromatography and gel filtration chromatography on Agarose P-100. It has a broad optimum from pH 6.0 to 9.0 and a temperature optimum of 45 degrees C for proteolytic activity on casein. It was classified as a metallo-protease by virtue of its inactivation by metal-ion chelators and reactivation by ferrous ions. Proteolytic activity was not affected by diiso-propylfluorophosphate, p-chloromercuribenzoate and dithiothreitol.", "contents": "The extracellular metalloprotease of Serratia marcescens: I. Purification and characterization. An extracellular protease of Serratia marcescens produced during growth on skim milk medium was isolated by ethanol precipitation. The protease was purified by salt fractionation, DEAE-cellulose ion exchange chromatography and gel filtration chromatography on Agarose P-100. It has a broad optimum from pH 6.0 to 9.0 and a temperature optimum of 45 degrees C for proteolytic activity on casein. It was classified as a metallo-protease by virtue of its inactivation by metal-ion chelators and reactivation by ferrous ions. Proteolytic activity was not affected by diiso-propylfluorophosphate, p-chloromercuribenzoate and dithiothreitol."}
{"id": "PMID:12466", "title": "[Juvenile rheumatoid arthritis and related collagen diseases. Clinical aspects (author's transl)].", "content": "Juvenile rheumatoid arthritis or, more correctly, juvenile chronic polyarthritis with its many clinical manifestations can be separated into the Still-syndrome with acute beginning, high fever and a high percentage of extra-articulalar, i.e. visceral symptoms, and the chronic polyarthritis in the more strict sense with non-visceral symptoms. The subsepsis allergica should be regarded as a subseptic first stage of the Still syndrome. The Still-syndrome implies a systemic disease mainly of the reticulo-endothelial system, with carditis, nephropathy, recurrent erythemas, and a progressing polyarthritis. Later symptoms are amyloidosis, chronic nephritis, myo- and pericarditis, and artheriitis necroticans. Predominanly the involvement of the kidneys is the reasons for the high mortality rate of 13%. Chronic polyarthritis in the strict sense is similar in children and adults, though in children rheumatic factors are rarely detected. The exsudative form of arthritis tends to cause early deterioration. Joint symptoms are distributed asymmetrically and show locally inflammed growth otherwise less common in Still-syndrome. Spondylitis cervicalis rapidly causes ankylosis. Atlanto-axial-arthritis with consequent atlanto-axial dislocation can be the reason for neurological disturbances. Juvenile mono- or oligo-arthritis often turns into polyarthritis; but for joints the prognosis is more favourable. In contrast, rheumatoid iridocyclitis as found in 22% of the cases causes unfavourable complications because symptoms are not noticed in time so that treatment is often too late. Juvenile spondylitis ankylosans begins with a peripheral arthritic stage which is not easily distinguished from chronic polyarthritis. The male sex, mono- or oligoarthritis of the outer extremities, pain in the heel, atlanto-axial-arthritis, iridocyclitis, and a positive HLA of 27 give a diagnostic clue. -- Characteristics of the therapy will be discussed.", "contents": "[Juvenile rheumatoid arthritis and related collagen diseases. Clinical aspects (author's transl)]. Juvenile rheumatoid arthritis or, more correctly, juvenile chronic polyarthritis with its many clinical manifestations can be separated into the Still-syndrome with acute beginning, high fever and a high percentage of extra-articulalar, i.e. visceral symptoms, and the chronic polyarthritis in the more strict sense with non-visceral symptoms. The subsepsis allergica should be regarded as a subseptic first stage of the Still syndrome. The Still-syndrome implies a systemic disease mainly of the reticulo-endothelial system, with carditis, nephropathy, recurrent erythemas, and a progressing polyarthritis. Later symptoms are amyloidosis, chronic nephritis, myo- and pericarditis, and artheriitis necroticans. Predominanly the involvement of the kidneys is the reasons for the high mortality rate of 13%. Chronic polyarthritis in the strict sense is similar in children and adults, though in children rheumatic factors are rarely detected. The exsudative form of arthritis tends to cause early deterioration. Joint symptoms are distributed asymmetrically and show locally inflammed growth otherwise less common in Still-syndrome. Spondylitis cervicalis rapidly causes ankylosis. Atlanto-axial-arthritis with consequent atlanto-axial dislocation can be the reason for neurological disturbances. Juvenile mono- or oligo-arthritis often turns into polyarthritis; but for joints the prognosis is more favourable. In contrast, rheumatoid iridocyclitis as found in 22% of the cases causes unfavourable complications because symptoms are not noticed in time so that treatment is often too late. Juvenile spondylitis ankylosans begins with a peripheral arthritic stage which is not easily distinguished from chronic polyarthritis. The male sex, mono- or oligoarthritis of the outer extremities, pain in the heel, atlanto-axial-arthritis, iridocyclitis, and a positive HLA of 27 give a diagnostic clue. -- Characteristics of the therapy will be discussed."}
{"id": "PMID:12467", "title": "[The ecology and medical importance of the Tahyna Virus (author's transl)].", "content": "In 1958 a virus transmitted by a mosquito was isolated in the Slovakian village of Tahyna. Since this virus was unknown in Europe, a detailed study was begun. It was shown that this virus belonged to the California group of arboviruses and occurs in practically all European countries. It could very well be that young hares are the hosts for this virus, and that it multiplies in them. Foals and suckling pigs are also hosts and possibly also increase the virus. In patients observed so far, infection with the Tahyna virus appears with influenza-like symptoms. In some cases, meningoencephalitis and atypical pneumonia were observed.", "contents": "[The ecology and medical importance of the Tahyna Virus (author's transl)]. In 1958 a virus transmitted by a mosquito was isolated in the Slovakian village of Tahyna. Since this virus was unknown in Europe, a detailed study was begun. It was shown that this virus belonged to the California group of arboviruses and occurs in practically all European countries. It could very well be that young hares are the hosts for this virus, and that it multiplies in them. Foals and suckling pigs are also hosts and possibly also increase the virus. In patients observed so far, infection with the Tahyna virus appears with influenza-like symptoms. In some cases, meningoencephalitis and atypical pneumonia were observed."}
{"id": "PMID:12468", "title": "Formation of mutagenic N-nitroso compounds from the pesticides prometryne, dodine and carbaryl in the presence of nitrite at pH 1.", "content": "Environmental chemicals including pesticides carrying secondary and tertiary amino groups are suggested to be a health hazard to man since potentially carcinogenic nitroso compounds may be formed in the presence of nitrite at low pH values resembling conditions in the human stomach. Nitrosation of the isopropylamino-triazine Prometryne, the n-dodecyl guanidine Dodine and the N-methylcarbamate carbaryl was investigated in the presence of HCl and acetic acid at pH 1 and excess sodium nitrite for 4 h at 37 degrees C. The reaction products were extracted with CCl4 and were analyzed qualitatively and quantitatively by infrared spectroscopy, nuclear-resonance spectrometry, GC/mass spectrometry and by spectrophotometry. All compounds investigated formed N-nitroso derivatives in the following yields: carbaryl 67%, Dodine 12% and Prometryne 14%. The N-nitroso derivatives per se were not or only slightly mutagenic to Escherichia coli K12 or Salmonella typhimurium TA 1538. However, significantly increased mutation frequencies were seen after metabolic activation by mouse-liver microsomes. These results add to the observations that among environmental chemicals not only those containing methyl- or ethyl-substituted amino groups form potentially carcinogenic nitroso derivatives but also those with iso-propylamino groups as well as alkyl-substituted guanidine derivatives.", "contents": "Formation of mutagenic N-nitroso compounds from the pesticides prometryne, dodine and carbaryl in the presence of nitrite at pH 1. Environmental chemicals including pesticides carrying secondary and tertiary amino groups are suggested to be a health hazard to man since potentially carcinogenic nitroso compounds may be formed in the presence of nitrite at low pH values resembling conditions in the human stomach. Nitrosation of the isopropylamino-triazine Prometryne, the n-dodecyl guanidine Dodine and the N-methylcarbamate carbaryl was investigated in the presence of HCl and acetic acid at pH 1 and excess sodium nitrite for 4 h at 37 degrees C. The reaction products were extracted with CCl4 and were analyzed qualitatively and quantitatively by infrared spectroscopy, nuclear-resonance spectrometry, GC/mass spectrometry and by spectrophotometry. All compounds investigated formed N-nitroso derivatives in the following yields: carbaryl 67%, Dodine 12% and Prometryne 14%. The N-nitroso derivatives per se were not or only slightly mutagenic to Escherichia coli K12 or Salmonella typhimurium TA 1538. However, significantly increased mutation frequencies were seen after metabolic activation by mouse-liver microsomes. These results add to the observations that among environmental chemicals not only those containing methyl- or ethyl-substituted amino groups form potentially carcinogenic nitroso derivatives but also those with iso-propylamino groups as well as alkyl-substituted guanidine derivatives."}
{"id": "PMID:12478", "title": "Thyrotropin releasing hormone (TRH): restoration of oxotremorine tremor in mice. Comparison with quipazine, a serotoninergic and dopaminergic stimulant.", "content": "Both TRH and quipazine (2.5-25 mg/kg) were found to restore and to intensify the oxotremorine-induced tremor in mice when injected i.p. 60 min after oxotremorine 0.5 mg/kg s.c. This phenomenon does not seem to be due to an increase in body temperature or muscle tone. Also other dopaminergic drugs, e.g. amphetamine, methylphenidate, nomifensine and apomorphine had a significant but lesser effect than TRH or quipazine. Haloperidol and methysergide both antagonized the effect of quipazine but not that of TRH. Neither propranolol, phenoxybenzamine, alpha-methyl-p-tyrosine, nor p-chlorophenylalanine inhibited the activity of TRH or quipazine. The restoration of oxotremorine-induced tremor could be prevented by atropine but not by methylatropine. It is concluded that quipazine exerts its effect by direct stimulation of serotoninergic and dopaminergic receptors, whereas TRH receptors may represent separate entities and TRH may function as a neurotransmitter or neuromodulator.", "contents": "Thyrotropin releasing hormone (TRH): restoration of oxotremorine tremor in mice. Comparison with quipazine, a serotoninergic and dopaminergic stimulant. Both TRH and quipazine (2.5-25 mg/kg) were found to restore and to intensify the oxotremorine-induced tremor in mice when injected i.p. 60 min after oxotremorine 0.5 mg/kg s.c. This phenomenon does not seem to be due to an increase in body temperature or muscle tone. Also other dopaminergic drugs, e.g. amphetamine, methylphenidate, nomifensine and apomorphine had a significant but lesser effect than TRH or quipazine. Haloperidol and methysergide both antagonized the effect of quipazine but not that of TRH. Neither propranolol, phenoxybenzamine, alpha-methyl-p-tyrosine, nor p-chlorophenylalanine inhibited the activity of TRH or quipazine. The restoration of oxotremorine-induced tremor could be prevented by atropine but not by methylatropine. It is concluded that quipazine exerts its effect by direct stimulation of serotoninergic and dopaminergic receptors, whereas TRH receptors may represent separate entities and TRH may function as a neurotransmitter or neuromodulator."}
{"id": "PMID:12477", "title": "Interaction of benzodiazepines with neuroleptics at central dopamine neurons.", "content": "Several benzodiazepines (chlordiazepoxide, clonazepam, diazepam and flunitrazepam) markedly counteracted the elevation of the homovanillic acid (HVA) content of the rat brain induced by neuroleptics (haloperidol, pimozide, chlorpromazine, and clozapine). A similar effect was obtained with the inhibitor of GABA transaminase, aminooxyacetic acid (AOAA). The interaction of benzodiazepines with the neuroleptic-induced HVA increase was similar in the striatum and in the limbic forebrain and was antagonized by the GABA receptor-blocking agent, picrotoxin. Both the benzodiazepines used and AOAA potentiated the cataleptic effect of the four neuroleptics. It is concluded that benzodiazepines, by intensifying GABA-ergic transmission, enhance the ongoing inhibition of mesencephalic dopamine neurons exerted by the striatonigral GABA system. As a consequence, the feedback activation of dopamine neurons induced by the neuroleptic blockade of dopamine receptors in the striatum and the limbic system is attenuated. This results in a reduction of the neuroleptic-induced increase of HVA and in the potentiation of the cataleptic effect of neuroleptics.", "contents": "Interaction of benzodiazepines with neuroleptics at central dopamine neurons. Several benzodiazepines (chlordiazepoxide, clonazepam, diazepam and flunitrazepam) markedly counteracted the elevation of the homovanillic acid (HVA) content of the rat brain induced by neuroleptics (haloperidol, pimozide, chlorpromazine, and clozapine). A similar effect was obtained with the inhibitor of GABA transaminase, aminooxyacetic acid (AOAA). The interaction of benzodiazepines with the neuroleptic-induced HVA increase was similar in the striatum and in the limbic forebrain and was antagonized by the GABA receptor-blocking agent, picrotoxin. Both the benzodiazepines used and AOAA potentiated the cataleptic effect of the four neuroleptics. It is concluded that benzodiazepines, by intensifying GABA-ergic transmission, enhance the ongoing inhibition of mesencephalic dopamine neurons exerted by the striatonigral GABA system. As a consequence, the feedback activation of dopamine neurons induced by the neuroleptic blockade of dopamine receptors in the striatum and the limbic system is attenuated. This results in a reduction of the neuroleptic-induced increase of HVA and in the potentiation of the cataleptic effect of neuroleptics."}
{"id": "PMID:12479", "title": "Effects of enzyme induction and inhibition on microsomal oxidation of 1,4-benzodiazepines.", "content": "Metabolic oxidative profiles of diazepam (I) were obtained by aromatic C-4'-hydroxylation, N-1-demethylation, and 3-hydroxylation using a supernatant of rat liver. Incubation of 3-methyldiazepam (VI), which suppressed 3-hydroxylation, and N-1-nor-3-methyldiazepam (VII), were used to separately investigate these three oxidative pathways. Treatment of animals with phenobarbital enhanced N-1-demethylation and 3-hydroxylation, and to a variable extent C-4'-hydroxylation. Application of metyrapone reduced metabolite formation by 3-hydroxylation and N-1-demethylation, but had no effect on C-4'-hydroxylation. Metyrapone inhibition was more pronounced following than prior to phenobarbital treatment. C-2-hydroxylation was studied using medazepam (XX) incubations. This pathway was increased by phenobarbital pretreatment and reduced by metyrapone inhibition which was again more pronounced following than prior to phenobarbital pretreatment. These results support earlier conclusions on the heterogeneity of liver microsomes and suggests the presence of different species of hepatic microsomal terminal oxidases. Phenobarbital treatment and metyrapone change the metabolic profile via induction and inhibition, respectively, and, thus, in the case of 1,4-benzodiazepines, the formation of metabolites with varying pharmacological activity. This could become important in clinical situations as a diagnostic mean to determine induction under various treatment or, possibly, during cumulation of metabolites with a long half-life.", "contents": "Effects of enzyme induction and inhibition on microsomal oxidation of 1,4-benzodiazepines. Metabolic oxidative profiles of diazepam (I) were obtained by aromatic C-4'-hydroxylation, N-1-demethylation, and 3-hydroxylation using a supernatant of rat liver. Incubation of 3-methyldiazepam (VI), which suppressed 3-hydroxylation, and N-1-nor-3-methyldiazepam (VII), were used to separately investigate these three oxidative pathways. Treatment of animals with phenobarbital enhanced N-1-demethylation and 3-hydroxylation, and to a variable extent C-4'-hydroxylation. Application of metyrapone reduced metabolite formation by 3-hydroxylation and N-1-demethylation, but had no effect on C-4'-hydroxylation. Metyrapone inhibition was more pronounced following than prior to phenobarbital treatment. C-2-hydroxylation was studied using medazepam (XX) incubations. This pathway was increased by phenobarbital pretreatment and reduced by metyrapone inhibition which was again more pronounced following than prior to phenobarbital pretreatment. These results support earlier conclusions on the heterogeneity of liver microsomes and suggests the presence of different species of hepatic microsomal terminal oxidases. Phenobarbital treatment and metyrapone change the metabolic profile via induction and inhibition, respectively, and, thus, in the case of 1,4-benzodiazepines, the formation of metabolites with varying pharmacological activity. This could become important in clinical situations as a diagnostic mean to determine induction under various treatment or, possibly, during cumulation of metabolites with a long half-life."}
{"id": "PMID:12480", "title": "Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium.", "content": "Electrophysiological and mechanical effects of histamine were observed in guinea-pig papillary muscle which had been depolarized and rendered inexcitable by elevation of potassium concentration in Tyrode solution to 27 mM. 1. Histamine (3 X 10(-7) to 3 X 10(-5) M) restored the action potential and tension development. The amplitude of the action potential was increased by 31.6 mV/10-fold increase in extracellular Ca2+ concentration. Nifedipine (10(-6) M) abolished the electrical and mechanical responses which had been restored by histamine (10(-5) M) but TTX (10(-5) M) did not affect them. Reduction of the extracellular Na+ concentration to one half decreased the amplitude and the maximum rate of rise of the action potential restored by histamine (10(-5) M) while the peak tension was increased and an after-contraction occurred. 2. The maximum rate of rise and the amplitude of the action potential restored by histamine (10(-5) M) decreased with increase in stimulus frequency from 0.1-1.6 Hz. The peak tension decreased and then increased. The shape of the developed tension was also changed. In the presence of caffeine (1 mM), the only effect of an increase in stimulus frequency was a decrease in peak tension but the change in the shape of developed tension did not occur. 3. The electrical and mechanical responses restored by histamine (3 X 10(-6) or 10(-5) M) were depressed by metiamide (3 X 10(-6) M) but not by diphenhydramine (10(-5) M) or bufetolol (10(-6) M). 4. The electrical response restored by histamine (10(-6) or 10(-5) M) was enhanced by papaverine (10(-5) M) and depressed by N-methylimidazole (10 mM). It is concluded that histamine may enhance the slow inward Ca2+ current mediated by histamine H2-receptors and the adenylate cyclase system in ventricular muscle and that the positive inotropic action of histamine may be attributed to these mechanisms.", "contents": "Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium. Electrophysiological and mechanical effects of histamine were observed in guinea-pig papillary muscle which had been depolarized and rendered inexcitable by elevation of potassium concentration in Tyrode solution to 27 mM. 1. Histamine (3 X 10(-7) to 3 X 10(-5) M) restored the action potential and tension development. The amplitude of the action potential was increased by 31.6 mV/10-fold increase in extracellular Ca2+ concentration. Nifedipine (10(-6) M) abolished the electrical and mechanical responses which had been restored by histamine (10(-5) M) but TTX (10(-5) M) did not affect them. Reduction of the extracellular Na+ concentration to one half decreased the amplitude and the maximum rate of rise of the action potential restored by histamine (10(-5) M) while the peak tension was increased and an after-contraction occurred. 2. The maximum rate of rise and the amplitude of the action potential restored by histamine (10(-5) M) decreased with increase in stimulus frequency from 0.1-1.6 Hz. The peak tension decreased and then increased. The shape of the developed tension was also changed. In the presence of caffeine (1 mM), the only effect of an increase in stimulus frequency was a decrease in peak tension but the change in the shape of developed tension did not occur. 3. The electrical and mechanical responses restored by histamine (3 X 10(-6) or 10(-5) M) were depressed by metiamide (3 X 10(-6) M) but not by diphenhydramine (10(-5) M) or bufetolol (10(-6) M). 4. The electrical response restored by histamine (10(-6) or 10(-5) M) was enhanced by papaverine (10(-5) M) and depressed by N-methylimidazole (10 mM). It is concluded that histamine may enhance the slow inward Ca2+ current mediated by histamine H2-receptors and the adenylate cyclase system in ventricular muscle and that the positive inotropic action of histamine may be attributed to these mechanisms."}
{"id": "PMID:12481", "title": "Inhibition by locally applied alpha-adrenoreceptor blocking drugs of the depressor response to stimulation of the anterior hypothalamus.", "content": "Cats were anaesthetized with pentobarbital sodium and the anterior hypothalamus was superfused with artificial cerebrospinal fluid through a push-pull cannula. Electrical stimulation of the superfused area with the tip of the cannula elicited a fall of the arterial blood pressure which was dependent on frequency and voltage. Maximal depressor response was obtained at 60 Hz with 2-4V; further increase of the voltage often led to a rise of the arterial blood pressure. Superfusion of the anterior hypothalamus with the alpha-adrenoreceptor blocking drugs tolazoline, piperoxan, yohimbine or phentolamine caused a dose-dependent inhibition of the depressor response to hypothalamic stimulation. Tolazoline was less effective than the other drugs. Superfusion of the anterior hypothalamus with the alpha-sympathomimetic drug phenylephrine prior to and during superfusion with phentolamine abolished the inhibitory action of the latter drug. It is concluded that alphaadrenoreceptors are present in the anterior hypothalamus and involved in the depressor response to electrical stimulation of this hypothalamic area.", "contents": "Inhibition by locally applied alpha-adrenoreceptor blocking drugs of the depressor response to stimulation of the anterior hypothalamus. Cats were anaesthetized with pentobarbital sodium and the anterior hypothalamus was superfused with artificial cerebrospinal fluid through a push-pull cannula. Electrical stimulation of the superfused area with the tip of the cannula elicited a fall of the arterial blood pressure which was dependent on frequency and voltage. Maximal depressor response was obtained at 60 Hz with 2-4V; further increase of the voltage often led to a rise of the arterial blood pressure. Superfusion of the anterior hypothalamus with the alpha-adrenoreceptor blocking drugs tolazoline, piperoxan, yohimbine or phentolamine caused a dose-dependent inhibition of the depressor response to hypothalamic stimulation. Tolazoline was less effective than the other drugs. Superfusion of the anterior hypothalamus with the alpha-sympathomimetic drug phenylephrine prior to and during superfusion with phentolamine abolished the inhibitory action of the latter drug. It is concluded that alphaadrenoreceptors are present in the anterior hypothalamus and involved in the depressor response to electrical stimulation of this hypothalamic area."}
{"id": "PMID:12482", "title": "Dopaminergic neurons: reversal of effects elicited by gamma-butyrolactone by stimulation of the nigro-neostriatal pathway.", "content": "In vivo studies demonstrate that administration of gamma-butyrolactone, a precursor of gamma-hydroxybutyric acid causes a rapid increase in endogenous levels of striatal dopamine and an increase in tyrosine hydroxylase activity measured by following the short term accumulation of dihydroxyphenylalanine. The increase in dopamine produced by GBL is blocked by stimulation of the nigro-neostriatal pathway. If dopamine is allowed to accumulate for 30 min following administration of GBL this increased dopamine can be released by stimulation of the nigro-neostriatal pathway. Maintenance of neuronal activity in the nigro-neostriatal pathway by continuous stimulation at a physiological frequency of 3/s effectively blocks the ability of GBL to cause an increase in tyrosine hydroxylase activity in the striatum on the stimulated side. Tyrosine hydroxylase activity in the non-stimulated contralateral striatum is increased over 100% by administration of GBL. Stimulation of the nigro-neostriatal pathway 30 min after GBL administration causes about a 500% increase in the accumulation of dihydroxyphenylacetic acid in the striatum on the stimulated side. These results suggest that the increased dopamine is present in a pool which is releasable by neuronal stimulation and is subsequently exposed to MAO. These results are also consistent with the hypothesis that GBL activates tyrosine hydroxylase and increases endogenous dopamine levels primarily by blocking impulse flow in central dopaminergic neurons.", "contents": "Dopaminergic neurons: reversal of effects elicited by gamma-butyrolactone by stimulation of the nigro-neostriatal pathway. In vivo studies demonstrate that administration of gamma-butyrolactone, a precursor of gamma-hydroxybutyric acid causes a rapid increase in endogenous levels of striatal dopamine and an increase in tyrosine hydroxylase activity measured by following the short term accumulation of dihydroxyphenylalanine. The increase in dopamine produced by GBL is blocked by stimulation of the nigro-neostriatal pathway. If dopamine is allowed to accumulate for 30 min following administration of GBL this increased dopamine can be released by stimulation of the nigro-neostriatal pathway. Maintenance of neuronal activity in the nigro-neostriatal pathway by continuous stimulation at a physiological frequency of 3/s effectively blocks the ability of GBL to cause an increase in tyrosine hydroxylase activity in the striatum on the stimulated side. Tyrosine hydroxylase activity in the non-stimulated contralateral striatum is increased over 100% by administration of GBL. Stimulation of the nigro-neostriatal pathway 30 min after GBL administration causes about a 500% increase in the accumulation of dihydroxyphenylacetic acid in the striatum on the stimulated side. These results suggest that the increased dopamine is present in a pool which is releasable by neuronal stimulation and is subsequently exposed to MAO. These results are also consistent with the hypothesis that GBL activates tyrosine hydroxylase and increases endogenous dopamine levels primarily by blocking impulse flow in central dopaminergic neurons."}
{"id": "PMID:12483", "title": "The action of a toxin from the sea anemone Anemonia sulcata upon Mammalian heart muscles.", "content": "The cardiac activity of toxin II, a basic polypeptide (m.w.: 4770) from the sea anemone Anemonia sulcata, was investigated in isolated electrically driven guinea-pig and rat auricles, Langendorff heart preparations of guinea-pigs and cat heart-lung preparations. Low concentrations of toxin II (2-100 nM) evoked a dose-dependent positive inotropic effect in the three different heart muscle preparations investigated. Higher concentrations of toxin II produced toxic symptoms like contracture and arrhythmia in auricles and atria (about 25 nM). In isolated cat hearts high toxin II concentrations (about 160 nM) caused unusual toxic symptoms such as long periods of ventricular fibrillation alternating with periods of normal cardiac activity. In rat and guinea-pig auricles as well as in Langendorff hearts of guinea-pigs the extent and rate of the positive inotropic effect induced by toxin II depended on the extracellular calcium concentration (0.45 to 2.7 mM). Toxin II did not alter the heart rate in spontaneously beating isolated cat hearts. In electrically driven guinea-pig auricles, the rate of the inotropic effect induced by toxin II was accelerated by increasing stimulation frequencies. Toxin II did not change the coronary flow in Langendorff heart preparations of guinea-pigs.", "contents": "The action of a toxin from the sea anemone Anemonia sulcata upon Mammalian heart muscles. The cardiac activity of toxin II, a basic polypeptide (m.w.: 4770) from the sea anemone Anemonia sulcata, was investigated in isolated electrically driven guinea-pig and rat auricles, Langendorff heart preparations of guinea-pigs and cat heart-lung preparations. Low concentrations of toxin II (2-100 nM) evoked a dose-dependent positive inotropic effect in the three different heart muscle preparations investigated. Higher concentrations of toxin II produced toxic symptoms like contracture and arrhythmia in auricles and atria (about 25 nM). In isolated cat hearts high toxin II concentrations (about 160 nM) caused unusual toxic symptoms such as long periods of ventricular fibrillation alternating with periods of normal cardiac activity. In rat and guinea-pig auricles as well as in Langendorff hearts of guinea-pigs the extent and rate of the positive inotropic effect induced by toxin II depended on the extracellular calcium concentration (0.45 to 2.7 mM). Toxin II did not alter the heart rate in spontaneously beating isolated cat hearts. In electrically driven guinea-pig auricles, the rate of the inotropic effect induced by toxin II was accelerated by increasing stimulation frequencies. Toxin II did not change the coronary flow in Langendorff heart preparations of guinea-pigs."}
{"id": "PMID:12484", "title": "[Clinical evaluation of oxypertine in anxiety conditions].", "content": "Oxypertine, a new anxiolytic drug related to the indolylazine compounds, was evaluated in a group of 30 patients, the majority with severe anxiety (acute or chronic) : in some cases depression was associated. The study was performed in the Psychiatric Department at the Centro Femenil de Rehabilitaci\u00f3n Social, in Mexico City. A special feature of this study was that patients were confined for a legal process and consequently with restricted liberty. All were females between 19 to 44 years old, with an average age of 32.05 years. The methodology applied in this case was a modified double blind randomized procedure, using different color capsules with placebo or the active drug (yellow oxypertine and blue placebo). Patients received a 10 mg capsule every 12 hours (20 mg daily). The clinical measurement of anxiety was performed using the Visual Anxiety Scale (Murphy), evaluating each of its 11 parameters. The intensity was qualified from 0 to 3; at the end of each consultation a global assessment was made. Most of the patients were interviewed in five occasions during the treatment period. For each of the nine patients receiving during 4 weeks only oxypertine capsules (group I), the scores of the parameters of the scale were added, observing the following results: in seven excellent respond, fair in one and one abandoned the study since the beginning. In eight of the patients who received placebo (group II) also for a 4 weeks period, results were evaluated as follows: five excellent one good and two poor. It can be observed that both groups gave a similar final score at the end of the study, meaning that no significant benefits were obtained between the active drug and the placebo, in spite that anxiety decreased in most of them. In group III, seven cases initiated with placebo and after 2 weeks the capsule had to be changed to oxypertine due to stablization or increase in the anxiety. Results were excellent in three, good in two, poor in one and another case suspended the treatment when placebo was to be substituted. In this same group, six cases initiated treatment with oxypertine, and after two weeks or more the medication was changed to placebo due to the same reasons mentioned above. Results were fair in one and poor in five. A significant response was observed in those cases where oxypertine replaced placebo and no response was obtained when placebo substituted oxypertine. Few cases abandoned mainly for two reasons: satisfactory remission of the anxiety or symptoms exacerbation. Investigators emphasize that the psychological conditions of the patients studied in this trial were different from the ones who ordinarily assist to the out patient clinics or private practice, mainly because were subjects with legal and social problems, as already mentioned, confined in a rehabilitation center. The conclusion of the stldy is that the administration of oxpertine at the dosage of 20 mg to patients with severe anxiety and with the special conditions mentioned above, provides a relative anxiolytic effect.", "contents": "[Clinical evaluation of oxypertine in anxiety conditions]. Oxypertine, a new anxiolytic drug related to the indolylazine compounds, was evaluated in a group of 30 patients, the majority with severe anxiety (acute or chronic) : in some cases depression was associated. The study was performed in the Psychiatric Department at the Centro Femenil de Rehabilitaci\u00f3n Social, in Mexico City. A special feature of this study was that patients were confined for a legal process and consequently with restricted liberty. All were females between 19 to 44 years old, with an average age of 32.05 years. The methodology applied in this case was a modified double blind randomized procedure, using different color capsules with placebo or the active drug (yellow oxypertine and blue placebo). Patients received a 10 mg capsule every 12 hours (20 mg daily). The clinical measurement of anxiety was performed using the Visual Anxiety Scale (Murphy), evaluating each of its 11 parameters. The intensity was qualified from 0 to 3; at the end of each consultation a global assessment was made. Most of the patients were interviewed in five occasions during the treatment period. For each of the nine patients receiving during 4 weeks only oxypertine capsules (group I), the scores of the parameters of the scale were added, observing the following results: in seven excellent respond, fair in one and one abandoned the study since the beginning. In eight of the patients who received placebo (group II) also for a 4 weeks period, results were evaluated as follows: five excellent one good and two poor. It can be observed that both groups gave a similar final score at the end of the study, meaning that no significant benefits were obtained between the active drug and the placebo, in spite that anxiety decreased in most of them. In group III, seven cases initiated with placebo and after 2 weeks the capsule had to be changed to oxypertine due to stablization or increase in the anxiety. Results were excellent in three, good in two, poor in one and another case suspended the treatment when placebo was to be substituted. In this same group, six cases initiated treatment with oxypertine, and after two weeks or more the medication was changed to placebo due to the same reasons mentioned above. Results were fair in one and poor in five. A significant response was observed in those cases where oxypertine replaced placebo and no response was obtained when placebo substituted oxypertine. Few cases abandoned mainly for two reasons: satisfactory remission of the anxiety or symptoms exacerbation. Investigators emphasize that the psychological conditions of the patients studied in this trial were different from the ones who ordinarily assist to the out patient clinics or private practice, mainly because were subjects with legal and social problems, as already mentioned, confined in a rehabilitation center. The conclusion of the stldy is that the administration of oxpertine at the dosage of 20 mg to patients with severe anxiety and with the special conditions mentioned above, provides a relative anxiolytic effect."}
{"id": "PMID:12487", "title": "Benzodiazepine-induced modifications of dream content: the effect of flunitrazepam.", "content": "The purpose of this study was to investigate the effect of flunitrazepam, a benzodiazepine with strong hypnotic properties, on dream content. Eight normal subjects were studied in laboratory by the awakening technique, and the dream contents were rated by two judges according to nine scaled dimensions: unreality, participation of the dreamer, pleasantness, unpleasantness, verbal aggresivity, physical aggressivity, sexuality, sensoriality and time of reference in the dreamer's life. By comparison with placebo condition, flunitrazepam induced more unpleasantness, more verbal aggressivity, more physical aggressivity, and more sexuality in dreams. This increase of emotionally loaded contents can be related to a disinhibitory effect of this drug, and the possible involvement of dopaminergic or serotoninergic systems is discussed.", "contents": "Benzodiazepine-induced modifications of dream content: the effect of flunitrazepam. The purpose of this study was to investigate the effect of flunitrazepam, a benzodiazepine with strong hypnotic properties, on dream content. Eight normal subjects were studied in laboratory by the awakening technique, and the dream contents were rated by two judges according to nine scaled dimensions: unreality, participation of the dreamer, pleasantness, unpleasantness, verbal aggresivity, physical aggressivity, sexuality, sensoriality and time of reference in the dreamer's life. By comparison with placebo condition, flunitrazepam induced more unpleasantness, more verbal aggressivity, more physical aggressivity, and more sexuality in dreams. This increase of emotionally loaded contents can be related to a disinhibitory effect of this drug, and the possible involvement of dopaminergic or serotoninergic systems is discussed."}
{"id": "PMID:12490", "title": "[Cases of enuresis nocturna treated with single reflexotherapy. Clinical and therapeutic evaluation].", "content": "Treatment of children with nocturnal enuresis by means of acupuncture, auriculotherapy, etc. is reported. The aetiopathogenetic background, the results of treatment, and the neurophysiological mechanisms through which the action of reflexotherapy can be explained are discussed.", "contents": "[Cases of enuresis nocturna treated with single reflexotherapy. Clinical and therapeutic evaluation]. Treatment of children with nocturnal enuresis by means of acupuncture, auriculotherapy, etc. is reported. The aetiopathogenetic background, the results of treatment, and the neurophysiological mechanisms through which the action of reflexotherapy can be explained are discussed."}
{"id": "PMID:12491", "title": "Practolol and the safety of other beta blockers.", "content": "Recognition of the \"occulomucocutaneous syndrome\" related to practolol administration has caused the safety of other beta-blocking agents to come under close scrutiny. No satisfactory means of screening for at-risk patients is available. ANF estimation, has considerable limitations as both a screening and a diagnostic procedure. Patients with skin lesions alone may not be positive, while even advanced cases often show very low titres. There are important technical difficulties with the assay and interpretation of results is hindered by an increase in incidence of the antibody with age, in females, and in patients on a wide variety of other therapeutic agents.", "contents": "Practolol and the safety of other beta blockers. Recognition of the \"occulomucocutaneous syndrome\" related to practolol administration has caused the safety of other beta-blocking agents to come under close scrutiny. No satisfactory means of screening for at-risk patients is available. ANF estimation, has considerable limitations as both a screening and a diagnostic procedure. Patients with skin lesions alone may not be positive, while even advanced cases often show very low titres. There are important technical difficulties with the assay and interpretation of results is hindered by an increase in incidence of the antibody with age, in females, and in patients on a wide variety of other therapeutic agents."}
{"id": "PMID:12492", "title": "Primary uterine tumors and multiple endocrine adenomatosis, type I.", "content": "Multiple endocrine adenomatosis, Type I was initially diagnosed in a 35-year-old woman with primary chief cell hyperplasia of the parathyroids. Approximately 5 years later, vaginal bleeding developed and a well-differentiated endometrial adenocarcinoma was recognized. An adenomatoid tumor of the uterus was discovered in addition to a nonfunctional islet cell tumor of the pancreas. Multiple endocrine adenomatosis is reviewed in relation to possible gynecologic neoplasms.", "contents": "Primary uterine tumors and multiple endocrine adenomatosis, type I. Multiple endocrine adenomatosis, Type I was initially diagnosed in a 35-year-old woman with primary chief cell hyperplasia of the parathyroids. Approximately 5 years later, vaginal bleeding developed and a well-differentiated endometrial adenocarcinoma was recognized. An adenomatoid tumor of the uterus was discovered in addition to a nonfunctional islet cell tumor of the pancreas. Multiple endocrine adenomatosis is reviewed in relation to possible gynecologic neoplasms."}
{"id": "PMID:12495", "title": "Phenylalanine hydroxylase and tyrosine aminotransferase in human fetal and adult liver.", "content": "The mean value of phenylalanine hydroxylase activity in adult human liver was almost twice as high as that in the fetal ones; no consistent variations were seen with sex, fetal age (between the 11th and 22nd week of gestation), or with hours between delivery and death. The tyrosine aminotransferase levels did not correlate with sex, age, or method of abortion; however, they were 5 times higher in the two fetuses which survived for more than 1.5 hr after delivery. The mean concentration of tyrosine aminotransferase (excluding these two fetuses) was about 15 times lower than in the adult liver. Phenylalanine hydroxylase is known to appear in rat liver on the 20th to 21st day of gestation. Tyrosine aminotransferase, on the other hand, emerges on the first postnatal day and, as shown here, can be evoked by premature delivery. Thus, in man as in the rat, (1) phenylalanine hydroxylase approaches physiologically significant levels at an earlier development stage than does tyrosine aminotransferase and (2) extrauterinization stimulates the synthesis of tyrosine aminotransferase but not of phenylalanine hydroxylase. Speculation There is a greater analogy than is usually assumed between human and rat liver with respect to the time schedule of enzymic differentiation and the factors which regulate it.", "contents": "Phenylalanine hydroxylase and tyrosine aminotransferase in human fetal and adult liver. The mean value of phenylalanine hydroxylase activity in adult human liver was almost twice as high as that in the fetal ones; no consistent variations were seen with sex, fetal age (between the 11th and 22nd week of gestation), or with hours between delivery and death. The tyrosine aminotransferase levels did not correlate with sex, age, or method of abortion; however, they were 5 times higher in the two fetuses which survived for more than 1.5 hr after delivery. The mean concentration of tyrosine aminotransferase (excluding these two fetuses) was about 15 times lower than in the adult liver. Phenylalanine hydroxylase is known to appear in rat liver on the 20th to 21st day of gestation. Tyrosine aminotransferase, on the other hand, emerges on the first postnatal day and, as shown here, can be evoked by premature delivery. Thus, in man as in the rat, (1) phenylalanine hydroxylase approaches physiologically significant levels at an earlier development stage than does tyrosine aminotransferase and (2) extrauterinization stimulates the synthesis of tyrosine aminotransferase but not of phenylalanine hydroxylase. Speculation There is a greater analogy than is usually assumed between human and rat liver with respect to the time schedule of enzymic differentiation and the factors which regulate it."}
{"id": "PMID:12496", "title": "Failure of parathyroid hormone and cyclic AMP to inhibit renal carbonic anhydrase.", "content": "It has been suggested that the parathyroid hormone and cyclic AMP produce their bicarbonaturic effects through inhibition of renal carbonic anhydrase. In the present study, the incubation of renal carbonic anhydrase with parathyroid hormone or cyclic AMP in presence of ATP, Mg++ and K+ ions, did not produce any inhibition of the enzyme when the pH of the solution was maintained above 7. It is concluded, that parathyroid hormone and cyclic AMP produce urinary bicarbonate excretion by a mechanism independent of carbonic anhydrase inhibition.", "contents": "Failure of parathyroid hormone and cyclic AMP to inhibit renal carbonic anhydrase. It has been suggested that the parathyroid hormone and cyclic AMP produce their bicarbonaturic effects through inhibition of renal carbonic anhydrase. In the present study, the incubation of renal carbonic anhydrase with parathyroid hormone or cyclic AMP in presence of ATP, Mg++ and K+ ions, did not produce any inhibition of the enzyme when the pH of the solution was maintained above 7. It is concluded, that parathyroid hormone and cyclic AMP produce urinary bicarbonate excretion by a mechanism independent of carbonic anhydrase inhibition."}
{"id": "PMID:12497", "title": "polA6, A mutation affecting the DNA binding capacity of DNA polymerase I.", "content": "The polA6 mutation is an allele of the polA gene of Escherichia coli which produces a DNA polymerase I species readily distinguishable from that produced by the wild type allele. Experiments described here show that this enzyme has an altered pH optimum for polymerization and a lower binding affinity for DNA. The defect clearly lies within the carboxyl-terminal large fragment of the enzyme produced by in vivo or in vitro proteolysis since the fragment has the same pH optimum for polymerization as the intact enzyme. The polA6 enzyme and its fragment are more sensitive to phosphate ions than the wild type polymerase, and the large fragment is less efficient at binding poly d(AT) in in vitro binding assays. Although the specific nucleolytic activity of the polA6 enzyme is higher than that of the wild type, there is no apparent alteration in pH optimum for the hydrolysis of eigher double or single stranded DNA.", "contents": "polA6, A mutation affecting the DNA binding capacity of DNA polymerase I. The polA6 mutation is an allele of the polA gene of Escherichia coli which produces a DNA polymerase I species readily distinguishable from that produced by the wild type allele. Experiments described here show that this enzyme has an altered pH optimum for polymerization and a lower binding affinity for DNA. The defect clearly lies within the carboxyl-terminal large fragment of the enzyme produced by in vivo or in vitro proteolysis since the fragment has the same pH optimum for polymerization as the intact enzyme. The polA6 enzyme and its fragment are more sensitive to phosphate ions than the wild type polymerase, and the large fragment is less efficient at binding poly d(AT) in in vitro binding assays. Although the specific nucleolytic activity of the polA6 enzyme is higher than that of the wild type, there is no apparent alteration in pH optimum for the hydrolysis of eigher double or single stranded DNA."}
{"id": "PMID:12498", "title": "Implications of electrostatic potentials on ribosomal proteins.", "content": "Potentiometric studies of ribosomal particles 30S, 50S, and 70S, were designed to investigate possible implications of the electrostatic potentials developed by the 16S and 23S rRNA fractions. Release of protons and proton titrations of these ribosomal fractions were examined as a function of Mg2+ and K+ concentrations. The effects of these cations fit the polyelectrolyte theory remarkably well and are discussed accordingly.", "contents": "Implications of electrostatic potentials on ribosomal proteins. Potentiometric studies of ribosomal particles 30S, 50S, and 70S, were designed to investigate possible implications of the electrostatic potentials developed by the 16S and 23S rRNA fractions. Release of protons and proton titrations of these ribosomal fractions were examined as a function of Mg2+ and K+ concentrations. The effects of these cations fit the polyelectrolyte theory remarkably well and are discussed accordingly."}
{"id": "PMID:12504", "title": "Volume changes in binding of ligands to methemoglobin and metmyoglobin.", "content": "The volume changes for the binding of various ligands to metmyoglobin and methemoglobin have been determined from the effect of pressure on the binding constants (for metmyoglobin) and by direct dilatometry (for methemoglobin). The volume changes associated with the binding of cyanide and azide ions to methemoglobin are pH-dependent. The volume change for the binding reaction is evidently affected by the same subtle structural variations that have been judged to be present from the variation with pH of enthalpy and entropy for the binding reactions in these proteins. Hydration changes and spin state changes which have been postulated to be linked with structural variations in these proteins must be pH-dependent.", "contents": "Volume changes in binding of ligands to methemoglobin and metmyoglobin. The volume changes for the binding of various ligands to metmyoglobin and methemoglobin have been determined from the effect of pressure on the binding constants (for metmyoglobin) and by direct dilatometry (for methemoglobin). The volume changes associated with the binding of cyanide and azide ions to methemoglobin are pH-dependent. The volume change for the binding reaction is evidently affected by the same subtle structural variations that have been judged to be present from the variation with pH of enthalpy and entropy for the binding reactions in these proteins. Hydration changes and spin state changes which have been postulated to be linked with structural variations in these proteins must be pH-dependent."}
{"id": "PMID:12505", "title": "Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.", "content": "In order to develop a better dopamine receptor radioligand, [3H[apomorphine was prepared and tested for dopamine-like binding properties in both calf and human brain tissues. Specific binding of [3H]apomorphine was defined as that binding which occurred in the presence of 1 muM (-)-butaclamol (an inactive neuroleptic) minus that occurring in the presence of 1 muM (+)-butaclamol (active neuroleptic). The specific binding was saturable, the number of sites being double that of specific [3H]dopamine binding, and occurred primarily in dopamine-rich regions of postmortem human brains. The binding had a dissociation constant of 0.9 nM for human caudate (2 nM for calf caudate) and was blocked by dopamine and norepinephrine, but not by isoproterenol or (-)-propranolol, distinguishing it from a beta-adrenergic receptor. Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor.", "contents": "Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug. In order to develop a better dopamine receptor radioligand, [3H[apomorphine was prepared and tested for dopamine-like binding properties in both calf and human brain tissues. Specific binding of [3H]apomorphine was defined as that binding which occurred in the presence of 1 muM (-)-butaclamol (an inactive neuroleptic) minus that occurring in the presence of 1 muM (+)-butaclamol (active neuroleptic). The specific binding was saturable, the number of sites being double that of specific [3H]dopamine binding, and occurred primarily in dopamine-rich regions of postmortem human brains. The binding had a dissociation constant of 0.9 nM for human caudate (2 nM for calf caudate) and was blocked by dopamine and norepinephrine, but not by isoproterenol or (-)-propranolol, distinguishing it from a beta-adrenergic receptor. Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor."}
{"id": "PMID:12503", "title": "[Effect of several factors on the process of protein solution ultrafiltration].", "content": "Ultrafiltration of protein solutions was investigated, using deoxyribonuclease of Actinomyces streptomycini filtered through a membrane based on vinylpyrrolidone-methyl methacrylate copolymers. It was shown that ionization of the protein molecule, level of the applied pressure as well as the protein concentration in the initial solution influenced particle adsorption on the surface and in pores of the molecule and the formation of gel layer reducing the rate of the solution filtration. The following parameters were found to favor the process: pH=7.5 (the value corresponds to the highest stability of the enzyme and the presence of the total negative discharge on the surface of the protein molecule). DNase concentration not more than 2 mg/ml, pressure 2 atm. The retaining capacity of the membrane was 85% and DNAase losses were 20%.", "contents": "[Effect of several factors on the process of protein solution ultrafiltration]. Ultrafiltration of protein solutions was investigated, using deoxyribonuclease of Actinomyces streptomycini filtered through a membrane based on vinylpyrrolidone-methyl methacrylate copolymers. It was shown that ionization of the protein molecule, level of the applied pressure as well as the protein concentration in the initial solution influenced particle adsorption on the surface and in pores of the molecule and the formation of gel layer reducing the rate of the solution filtration. The following parameters were found to favor the process: pH=7.5 (the value corresponds to the highest stability of the enzyme and the presence of the total negative discharge on the surface of the protein molecule). DNase concentration not more than 2 mg/ml, pressure 2 atm. The retaining capacity of the membrane was 85% and DNAase losses were 20%."}
{"id": "PMID:12506", "title": "Isolation of 3-phosphohistidine from phosphorylated pyruvate, phosphate dikinase.", "content": "Pyruvate, phosphate dikinase (EC 2-7-9-1) catalyzes formation of phosphoenolpyruvate, AMP, and inorganic pyrophosphate from pyruvate, ATP, and orthophosphate. A pyrophosphoryl and phosphoryl form of the enzyme is involved in this transfer. The [32P]phosphoryl form of pyruvate, phosphate dikinase was prepared with enzyme isolated from Bacteroides symbiosus. The [32P]phosphoryl enzyme was found to have properties corresponding to a phosphoramidate linkage and this was confirmed by isolation of 3-[32P]phosphohistidine from alkaline hydrolysates of the enzyme. The histidyl residue is considered to be the pyrophosphoryl- and phosphoryl-carrier between the three substrate sites of this enzyme.", "contents": "Isolation of 3-phosphohistidine from phosphorylated pyruvate, phosphate dikinase. Pyruvate, phosphate dikinase (EC 2-7-9-1) catalyzes formation of phosphoenolpyruvate, AMP, and inorganic pyrophosphate from pyruvate, ATP, and orthophosphate. A pyrophosphoryl and phosphoryl form of the enzyme is involved in this transfer. The [32P]phosphoryl form of pyruvate, phosphate dikinase was prepared with enzyme isolated from Bacteroides symbiosus. The [32P]phosphoryl enzyme was found to have properties corresponding to a phosphoramidate linkage and this was confirmed by isolation of 3-[32P]phosphohistidine from alkaline hydrolysates of the enzyme. The histidyl residue is considered to be the pyrophosphoryl- and phosphoryl-carrier between the three substrate sites of this enzyme."}
{"id": "PMID:12507", "title": "Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue.", "content": "The intact heart of a young rat was excised rapidly and cooled to 0 degree C; its energy-rich compounds were examined by 31P Fourier Transform nuclear magnetic resonance. The heart showed the characteristic spectrum of sugar phosphates, inorganic phosphate, phosphocreatine, and magniesium phates, inorganic phosphate, phosphocreatine, and magnesium ATP, characteristics of the energizing state of the nonbeating tissue. Warming to 30 degrees C imposes an energy load upon the heart consistent with short-term resumption of beating, concomitant intracellular acidosis, and decomposition of all detectable energy-rich compounds. The intracellular acidity causes a shift from pH 7.0 to 6.0. The effects of possible interferences with this pH measurement are considered. The method appears to have wide usefulness in cardiac infarct models for detecting the fraction of the total volume occupied by the infarct and for studying the effect of various proposed therapies upon this infarcted volume.", "contents": "Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue. The intact heart of a young rat was excised rapidly and cooled to 0 degree C; its energy-rich compounds were examined by 31P Fourier Transform nuclear magnetic resonance. The heart showed the characteristic spectrum of sugar phosphates, inorganic phosphate, phosphocreatine, and magniesium phates, inorganic phosphate, phosphocreatine, and magnesium ATP, characteristics of the energizing state of the nonbeating tissue. Warming to 30 degrees C imposes an energy load upon the heart consistent with short-term resumption of beating, concomitant intracellular acidosis, and decomposition of all detectable energy-rich compounds. The intracellular acidity causes a shift from pH 7.0 to 6.0. The effects of possible interferences with this pH measurement are considered. The method appears to have wide usefulness in cardiac infarct models for detecting the fraction of the total volume occupied by the infarct and for studying the effect of various proposed therapies upon this infarcted volume."}
{"id": "PMID:12508", "title": "Role of the intrinsic transglutaminase in the Ca2+-mediated crosslinking of erythrocyte proteins.", "content": "Transamidase (i.e., \"transglutaminase\") activity of human erythrocytes, lysed by a single freezing and thawing to 37 degrees, was measured by a method of incorporating [14C]putrescine into N,N'-dimethylcasein. In the absence of added calcium ions, virtually no enzyme activity could be detected. An increase in concentration of the cation to about 0.5 mM, however, turned on the enzyme to appreciable levels of activity. Simultaneously, Ca2+ produced formation of high molecular weight, nondisulfied bonded protein polymers either directly in the lysate or in fresh cells when the cation was added together with the A23187 ionophore. The polymers could be readily identified in the isolated cell ghosts by means of disc gel electrophoresis. If the Ca2+-promoted formation of polymers was allowed to take place in the presence of 14C-putrescine, then this tracer became incorporated into the polymeric material. The incorporation indicated that polymerization occurred through gamma-glutamyl-epsilon-lysine bridtes. It is suggested that the intrinsic transamidase mediates protein crosslinking of the erythrocyte membrane whenever there is an increase in intracellular Ca2+ concentration. The presence of suitable transglutaminase substrates, e.g. histamine, inhibited crosslinking when the cells were incubated with Ca2+ and ionophore.", "contents": "Role of the intrinsic transglutaminase in the Ca2+-mediated crosslinking of erythrocyte proteins. Transamidase (i.e., \"transglutaminase\") activity of human erythrocytes, lysed by a single freezing and thawing to 37 degrees, was measured by a method of incorporating [14C]putrescine into N,N'-dimethylcasein. In the absence of added calcium ions, virtually no enzyme activity could be detected. An increase in concentration of the cation to about 0.5 mM, however, turned on the enzyme to appreciable levels of activity. Simultaneously, Ca2+ produced formation of high molecular weight, nondisulfied bonded protein polymers either directly in the lysate or in fresh cells when the cation was added together with the A23187 ionophore. The polymers could be readily identified in the isolated cell ghosts by means of disc gel electrophoresis. If the Ca2+-promoted formation of polymers was allowed to take place in the presence of 14C-putrescine, then this tracer became incorporated into the polymeric material. The incorporation indicated that polymerization occurred through gamma-glutamyl-epsilon-lysine bridtes. It is suggested that the intrinsic transamidase mediates protein crosslinking of the erythrocyte membrane whenever there is an increase in intracellular Ca2+ concentration. The presence of suitable transglutaminase substrates, e.g. histamine, inhibited crosslinking when the cells were incubated with Ca2+ and ionophore."}
{"id": "PMID:12509", "title": "Proline and glycine uptake by renal brushborder membrane vesicles.", "content": "Uptake of L-proline and glycine by rat renal brushborder membrane vesicles was seen to be osmotically sensitive, pH dependent,and occurred in the absence of proline and glycine metabolism. The uptake system for proline was Na+ gradient dependent, and exhibited a dual system for entry, Km1 = 0.067 mM and Km2 = 5.26 mM. The uptake of glycine was also Na+ gradient dependent, and exhibited a two Km system, Km1 = 0.22 mM and Km2 = 4.00 mM. Studies of proline and glycine interactions indicate a shared site which has a lower affinity and higher capacity for glycine than for proline. The high affinity glycine site and low affinity proline site do not appear to be shared.", "contents": "Proline and glycine uptake by renal brushborder membrane vesicles. Uptake of L-proline and glycine by rat renal brushborder membrane vesicles was seen to be osmotically sensitive, pH dependent,and occurred in the absence of proline and glycine metabolism. The uptake system for proline was Na+ gradient dependent, and exhibited a dual system for entry, Km1 = 0.067 mM and Km2 = 5.26 mM. The uptake of glycine was also Na+ gradient dependent, and exhibited a two Km system, Km1 = 0.22 mM and Km2 = 4.00 mM. Studies of proline and glycine interactions indicate a shared site which has a lower affinity and higher capacity for glycine than for proline. The high affinity glycine site and low affinity proline site do not appear to be shared."}
{"id": "PMID:12518", "title": "Discriminative stimulus properties of fentanyl and morphine: tolerance and dependence.", "content": "Using a food-reinforced two-lever operant procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. At different time intervals after the establishment of discriminative responding, stimulus generalization experiments were performed with equivalent dose ranges of fentanyl (0.0025 to 0.02 mg/kg) and morphine (2.5 to 20 mg/kg). It was found that the ED50 values of both compounds for generalization with the narcotic discriminative stimulus complex, did not change over a 4-month period. The subjects used in this study demonstrated marked tolerance to narcotic analgesia, but none of them showed signs reminescent of narcotic dependence. It is concluded that the discriminative stimulus properties of narcotic analgesics are not subject to tolerance.", "contents": "Discriminative stimulus properties of fentanyl and morphine: tolerance and dependence. Using a food-reinforced two-lever operant procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. At different time intervals after the establishment of discriminative responding, stimulus generalization experiments were performed with equivalent dose ranges of fentanyl (0.0025 to 0.02 mg/kg) and morphine (2.5 to 20 mg/kg). It was found that the ED50 values of both compounds for generalization with the narcotic discriminative stimulus complex, did not change over a 4-month period. The subjects used in this study demonstrated marked tolerance to narcotic analgesia, but none of them showed signs reminescent of narcotic dependence. It is concluded that the discriminative stimulus properties of narcotic analgesics are not subject to tolerance."}
{"id": "PMID:12519", "title": "Early processing of visual information.", "content": "An introduction is given to a theory of early visual information processing. The theory has been implemented, and examples are given of images at various stages of analysis. It is argued that the first step of consequence is to compute a primitive but rich description of the grey-level changes present in an image. The description is expressed in a vocabulary of kinds of intensity change (EDGE, SHADING-EDGE, EXTENDED-EDGE, LINE, BLOB etc.). Modifying parameters are bound to the elements in the description, specifying their POSITION, ORIENTATION, TERMINATION points, CONTRAST, SIZE and FUZZINESS. This description is obtained from the intensity array by fixed techniques, and it is called the primal sketch. For most images, the primal sketch is large and unwieldy. The second important step in visual information processing is to group its contents in a way that is appropriate for later recognition. From our ability to interpret drawings with little semantic content, one may infer the presence in our perceptual equipment of symbolic processes that can define \"place-tokens\" in an image in various ways, and can group them according to certain rules. Homomorphic techniques fail to account for many of these grouping phenomena, whose explanations require mechanisms of construction rather than mechanisms of detection. The necessary grouping of elements in the primal sketch may be achieved by a mechanism that has available the processes inferred from above, together with the ability to select items by first order discriminations acting on the elements' parameters. Only occasionally do these mechanisms use downward-flowing information about the contents of the particular image being processed. It is argued that \"non-attentive\" vision is in practice implemented by these grouping operations and first order discriminations acting on the primal sketch. The class of computations so obtained differs slightly from the class of second order operations on the intensity array. The extraction of a form from the primal sketch using these techniques amounts to the separation of figure from ground. It is concluded that most of the separation can be carried out by using techniques that do not depend upon the particular image in question. Therefore, figure-ground separation can normally precede the description of the shape of the extracted form. Up to this point, higher-level knowledge and purpose are brought to bear on only a few of the decisions taken during the processing. This relegates the widespread use of downward-flowing information to a later stage than is found in current machine-vision programs, and implies that such knowledge should influence the control of, rather than interfering with, the actual data-processing that is taking place lower down.", "contents": "Early processing of visual information. An introduction is given to a theory of early visual information processing. The theory has been implemented, and examples are given of images at various stages of analysis. It is argued that the first step of consequence is to compute a primitive but rich description of the grey-level changes present in an image. The description is expressed in a vocabulary of kinds of intensity change (EDGE, SHADING-EDGE, EXTENDED-EDGE, LINE, BLOB etc.). Modifying parameters are bound to the elements in the description, specifying their POSITION, ORIENTATION, TERMINATION points, CONTRAST, SIZE and FUZZINESS. This description is obtained from the intensity array by fixed techniques, and it is called the primal sketch. For most images, the primal sketch is large and unwieldy. The second important step in visual information processing is to group its contents in a way that is appropriate for later recognition. From our ability to interpret drawings with little semantic content, one may infer the presence in our perceptual equipment of symbolic processes that can define \"place-tokens\" in an image in various ways, and can group them according to certain rules. Homomorphic techniques fail to account for many of these grouping phenomena, whose explanations require mechanisms of construction rather than mechanisms of detection. The necessary grouping of elements in the primal sketch may be achieved by a mechanism that has available the processes inferred from above, together with the ability to select items by first order discriminations acting on the elements' parameters. Only occasionally do these mechanisms use downward-flowing information about the contents of the particular image being processed. It is argued that \"non-attentive\" vision is in practice implemented by these grouping operations and first order discriminations acting on the primal sketch. The class of computations so obtained differs slightly from the class of second order operations on the intensity array. The extraction of a form from the primal sketch using these techniques amounts to the separation of figure from ground. It is concluded that most of the separation can be carried out by using techniques that do not depend upon the particular image in question. Therefore, figure-ground separation can normally precede the description of the shape of the extracted form. Up to this point, higher-level knowledge and purpose are brought to bear on only a few of the decisions taken during the processing. This relegates the widespread use of downward-flowing information to a later stage than is found in current machine-vision programs, and implies that such knowledge should influence the control of, rather than interfering with, the actual data-processing that is taking place lower down."}
{"id": "PMID:12520", "title": "Modification of the noradrenaline related effects of smoking by beta-blockade.", "content": "Increases in plasma noradrenaline were found in a group of 12 subjects smoking cigarettes. The associated rises in pulse rate, blood pressure and plasma free fatty acids could be prevented by beta-blockade with oxprenolol. This inhibition of the peripheral effects of catecholamines did not affect subjective satisfaction, indicating that central effects or other rewards are more important reinforcers. It is suggested that noradrenaline release in the hypothalamus is the final common pathway to pleasure in many situations, including smoking.", "contents": "Modification of the noradrenaline related effects of smoking by beta-blockade. Increases in plasma noradrenaline were found in a group of 12 subjects smoking cigarettes. The associated rises in pulse rate, blood pressure and plasma free fatty acids could be prevented by beta-blockade with oxprenolol. This inhibition of the peripheral effects of catecholamines did not affect subjective satisfaction, indicating that central effects or other rewards are more important reinforcers. It is suggested that noradrenaline release in the hypothalamus is the final common pathway to pleasure in many situations, including smoking."}
{"id": "PMID:12521", "title": "Psychoactive drug effect on behavioural changes induced by prolonged socio-environmental deprivation in rats.", "content": "Several so-called 'non-specific' or 'non-drug' factors are known to interfere with the response to psychotropic drug administration. Animal emotionality has been reported to change the outcome of psychoactive drug administration, so that the response to a stimulant or depressant drug may considerably change according to the baseline state of activity of the central nervous system. Prolonged socio-encironmental deprivation or isolation has been shown to produce in rats three different types of abnormal behaviour which have been tentatively defined as 'friendly', 'indifferent' and 'muricide'. Such unusual changes in rat behaviour are assumed to reflect a series of different emotional changes. The present experiments show that psychoactive drugs can exert a different effect in relation to the different kinds of animal behaviour used in the experiments. The investigation of the properties of psychoactive compounds, as performed in experimental animals showing behavioural alterations, is then suggested as being more fruitful in providing much information closer to the clinical results than that achieved with the experiments performed in normal laboratory animals.", "contents": "Psychoactive drug effect on behavioural changes induced by prolonged socio-environmental deprivation in rats. Several so-called 'non-specific' or 'non-drug' factors are known to interfere with the response to psychotropic drug administration. Animal emotionality has been reported to change the outcome of psychoactive drug administration, so that the response to a stimulant or depressant drug may considerably change according to the baseline state of activity of the central nervous system. Prolonged socio-encironmental deprivation or isolation has been shown to produce in rats three different types of abnormal behaviour which have been tentatively defined as 'friendly', 'indifferent' and 'muricide'. Such unusual changes in rat behaviour are assumed to reflect a series of different emotional changes. The present experiments show that psychoactive drugs can exert a different effect in relation to the different kinds of animal behaviour used in the experiments. The investigation of the properties of psychoactive compounds, as performed in experimental animals showing behavioural alterations, is then suggested as being more fruitful in providing much information closer to the clinical results than that achieved with the experiments performed in normal laboratory animals."}
{"id": "PMID:12522", "title": "Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain.", "content": "There is evidence that changes in the concentrations of the monoamine neurotransmitters within the brain are associated with changes in mental processes, with disorders of control of movement and with certain neuropsychiatric diseases. These neurotransmitters are synthesized in the brain from aromatic amino acid precursors that have to be obtained from the circulating blood. In this study some factors which alter the rates of entry of four amino acids (the important neurotransmitter precursors L-tyrosine and L-tryptophan, as well as L-phenylalanine and L-histidine) into the brain have been studied and the findings considered in relation to conditions in which the quantities of one or more of the monoamine neurotransmitters formed within the cerebral cells may be either too large or too small. Thus too little neurotransmitter will be formed if competition between amino acids for the carriers transporting them into the cerebral cells causes the exclusion of a large proportion of any of the aromatic amino acid precursors from the brain. ,or example, L-tryptophan is partially excluded from the brain if a raised level of any one of several other amino acids is maintained in the circulation. Of these, L-phenylalanine inhibits the transport of L-tryptophan into the brain most effectively, while aromatic amino acids in general exclude L-tryptophan more effectively than do other neutral amino acids. Over-production of one or more of the monoamine neurotransmitters is likely to occur when there is too much of one of the aromatic amino acid precursors in the brain cells as a result of abnormally high uptake from the blood, or as a result of their release by an excessive breakdown of the protein within these cells. Underproduction of neurotransmitters may occur in certain disease states, such as some aminoacidurias or Parkinsonism. We have listed some conditions associated with altered mental states or motor disability in which over- or under-production of monoamine neurotransmitters may occur and have tried to relate the findings in human disease with our experimental results.", "contents": "Amino acid precursors of monoamine neurotransmitters and some factors influencing their supply to the brain. There is evidence that changes in the concentrations of the monoamine neurotransmitters within the brain are associated with changes in mental processes, with disorders of control of movement and with certain neuropsychiatric diseases. These neurotransmitters are synthesized in the brain from aromatic amino acid precursors that have to be obtained from the circulating blood. In this study some factors which alter the rates of entry of four amino acids (the important neurotransmitter precursors L-tyrosine and L-tryptophan, as well as L-phenylalanine and L-histidine) into the brain have been studied and the findings considered in relation to conditions in which the quantities of one or more of the monoamine neurotransmitters formed within the cerebral cells may be either too large or too small. Thus too little neurotransmitter will be formed if competition between amino acids for the carriers transporting them into the cerebral cells causes the exclusion of a large proportion of any of the aromatic amino acid precursors from the brain. ,or example, L-tryptophan is partially excluded from the brain if a raised level of any one of several other amino acids is maintained in the circulation. Of these, L-phenylalanine inhibits the transport of L-tryptophan into the brain most effectively, while aromatic amino acids in general exclude L-tryptophan more effectively than do other neutral amino acids. Over-production of one or more of the monoamine neurotransmitters is likely to occur when there is too much of one of the aromatic amino acid precursors in the brain cells as a result of abnormally high uptake from the blood, or as a result of their release by an excessive breakdown of the protein within these cells. Underproduction of neurotransmitters may occur in certain disease states, such as some aminoacidurias or Parkinsonism. We have listed some conditions associated with altered mental states or motor disability in which over- or under-production of monoamine neurotransmitters may occur and have tried to relate the findings in human disease with our experimental results."}
{"id": "PMID:12524", "title": "Effects of chlordiazepoxide, ripazepam and d-amphetamine on conditioned acceleration of timing behaviour in rats.", "content": "The lever-pressing behaviour of three rats was maintained by a schedule in which food reinforcement was obtained by any response which was emitted at least 15 s after the previous response (DRL 15s). When performance on this schedule had stabilised, the animals were presented intermittently with 1-min periods of a white noise stimulus, the termination of which was accompanied by the delivery of a mild electric footshock. This procedure let to reliable increases in response rates furing the stimulus although responding at other times continued to be appropriate to the DRL 15-s schedule. Administration of the benzodiazepine chlordiazepoxide (1, 3, 10, 17 and 30 mg/kg) and of ripazepam (1, 3, 10, 30 and 56 mg/kg), a non-benzodiazepine reported to have anxiolytic properties, increased response rates on the DRL baseline while decreasing the acceleration of responding produced by the preshock stimulus. Baseline response rates were also increased by d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) and at the higher doses this drug completely abolished the accelerated responding during the preshock stimulus. Although the effects of chlordiazepoxide and ripazepam are consistent with the suggestion that these drugs may attenuate the behavioural effects of aversive stimuli, in this experiment the behavioural effects of d-amphetamine were similar in many respects.", "contents": "Effects of chlordiazepoxide, ripazepam and d-amphetamine on conditioned acceleration of timing behaviour in rats. The lever-pressing behaviour of three rats was maintained by a schedule in which food reinforcement was obtained by any response which was emitted at least 15 s after the previous response (DRL 15s). When performance on this schedule had stabilised, the animals were presented intermittently with 1-min periods of a white noise stimulus, the termination of which was accompanied by the delivery of a mild electric footshock. This procedure let to reliable increases in response rates furing the stimulus although responding at other times continued to be appropriate to the DRL 15-s schedule. Administration of the benzodiazepine chlordiazepoxide (1, 3, 10, 17 and 30 mg/kg) and of ripazepam (1, 3, 10, 30 and 56 mg/kg), a non-benzodiazepine reported to have anxiolytic properties, increased response rates on the DRL baseline while decreasing the acceleration of responding produced by the preshock stimulus. Baseline response rates were also increased by d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) and at the higher doses this drug completely abolished the accelerated responding during the preshock stimulus. Although the effects of chlordiazepoxide and ripazepam are consistent with the suggestion that these drugs may attenuate the behavioural effects of aversive stimuli, in this experiment the behavioural effects of d-amphetamine were similar in many respects."}
{"id": "PMID:12525", "title": "Head twitches induced by benzodiazepines and the role of biogenic amines.", "content": "Clonazepam, one of the benzodiazepines, induced head twitches in mice in a dose-dependent manner and sustained them for at least 120 min. Some of the benzodiazepines such as nitrazepam, fludiazepam, and nimetazepam also significantly induced head twitches at doses higher than 10 mg/kg, but other benzodiazepines like diazepam, flurazepam, oxazepam, medazepam, and chlordiazepoxide did not significantly induce head twitches at doses up to 60 mg/kg. The head twitches induced by clonazepam were more strongly blocked by a n antiserotonin drug, cyproheptadine than catecholamine receptor blocking drugs, haloperidol, propranolol, and phentolamine, and were not blocked by GABA receptor blocking drugs, bicuculline and picrotoxin, as well as by a glycine receptor blocking drug, strychnine. Clonazepam also increased the head twitches induced by mescaline, a serotonin receptor stimulant. These results indicate that the head twitches induced by clonazepam might be mediated via serotonergic neuron systems.", "contents": "Head twitches induced by benzodiazepines and the role of biogenic amines. Clonazepam, one of the benzodiazepines, induced head twitches in mice in a dose-dependent manner and sustained them for at least 120 min. Some of the benzodiazepines such as nitrazepam, fludiazepam, and nimetazepam also significantly induced head twitches at doses higher than 10 mg/kg, but other benzodiazepines like diazepam, flurazepam, oxazepam, medazepam, and chlordiazepoxide did not significantly induce head twitches at doses up to 60 mg/kg. The head twitches induced by clonazepam were more strongly blocked by a n antiserotonin drug, cyproheptadine than catecholamine receptor blocking drugs, haloperidol, propranolol, and phentolamine, and were not blocked by GABA receptor blocking drugs, bicuculline and picrotoxin, as well as by a glycine receptor blocking drug, strychnine. Clonazepam also increased the head twitches induced by mescaline, a serotonin receptor stimulant. These results indicate that the head twitches induced by clonazepam might be mediated via serotonergic neuron systems."}
{"id": "PMID:12526", "title": "Action of enpiprazole on emotional behavior induced by hypothalamic stimulation in rats and cats.", "content": "Action of enpiprazole on emotional behavior elicited by hypothalamic stimulation in rats and cats was investigated and comparisons were made with effects of diazepam. Two behavioral patterns were elicited by stimulation of the postero-medial part of the hypothalamus in rats: a food-carrying response beginning with exploratory movement and an analogue of fear. Enpiprazole frequently changed the food-carrying response into food-taking response and occasionally analogues of fear into food-carrying and /or food-taking responses. Thresholds for these behaviors were also elevated. Diazepam showed the same effects on the thresholds as enpiprazole, having but little effect on the behavioral patterns.  In cats, enpiprazole evelvated the thresholds for affective-defensive responses induced by hypothalamic stimulation in 6 of 8 cases, but lowered them in 2 cases. This suggests that enpiprazple has a 'biphasic effect' in the central nervous system. By contrast,diazepam consistently elevated thresholds. Comparing the action of enpiprazole with that of diazepam it can be presumed that the former is a different type of anxiolytic drug than the latter.", "contents": "Action of enpiprazole on emotional behavior induced by hypothalamic stimulation in rats and cats. Action of enpiprazole on emotional behavior elicited by hypothalamic stimulation in rats and cats was investigated and comparisons were made with effects of diazepam. Two behavioral patterns were elicited by stimulation of the postero-medial part of the hypothalamus in rats: a food-carrying response beginning with exploratory movement and an analogue of fear. Enpiprazole frequently changed the food-carrying response into food-taking response and occasionally analogues of fear into food-carrying and /or food-taking responses. Thresholds for these behaviors were also elevated. Diazepam showed the same effects on the thresholds as enpiprazole, having but little effect on the behavioral patterns.  In cats, enpiprazole evelvated the thresholds for affective-defensive responses induced by hypothalamic stimulation in 6 of 8 cases, but lowered them in 2 cases. This suggests that enpiprazple has a 'biphasic effect' in the central nervous system. By contrast,diazepam consistently elevated thresholds. Comparing the action of enpiprazole with that of diazepam it can be presumed that the former is a different type of anxiolytic drug than the latter."}
{"id": "PMID:12527", "title": "Single and repeated administration of neuroleptic drugs to rats: effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-Dopa.", "content": "Injection of tranylcypromine and L-tryptophan results in rats displaying behavioural changes including hyperactivity, probably due to stimulation of post-synaptic 5-hydroxytryptamine (5-HT) receptors. Increased locomotor activity of a different type is elicited by injection of tranylcypromine and L-dopa, a procedure which increased dopaminergic function in the brain. It has now been demonstrated that the neuroleptic drugs, chlorpromazine, alpha-flupenthixol, haloperidol and spiroperidol block both syndromes. The inhibition produced by these drugs on 5-HT-induced hyperactivity is probably because a dopaminergic system is involved in the behavioural expression of the 5-HT induced hyperactivity. The structurally related drugs with no neuroleptic activity (ethopropazine, promethazine and beta-flupenthixol)are without effect on thses hyperactivity syndromes. Also ineffective were the neuroleptics pimozide and clozapine. Striatal dopamine sensitive adenylate cyclase activity in vitro was inhibited by the administration of chlorpromazine (100 mg/kg) in vivo. Rats treated for 4 or more days with chlorpromazine, alpha-flupenthixol, spiroperidol and haloperidol subsequently showed enhanced locomotor activity in response to tranylcypromine and L-Dopa. Administration of those drugs which did not block hyperactivity acutely did not result in enhancement. Only chlorpromazine, when given for 4 days, enhanced the hyperactivity response following tranylcypromine and L-tryptophan, probably because the drug also blocks 5-HT receptors. In rats displaying enhanced behavioural responses no evidence was found for enhanced sensitivity of striatal adenylate cyclase to dopamine.", "contents": "Single and repeated administration of neuroleptic drugs to rats: effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-Dopa. Injection of tranylcypromine and L-tryptophan results in rats displaying behavioural changes including hyperactivity, probably due to stimulation of post-synaptic 5-hydroxytryptamine (5-HT) receptors. Increased locomotor activity of a different type is elicited by injection of tranylcypromine and L-dopa, a procedure which increased dopaminergic function in the brain. It has now been demonstrated that the neuroleptic drugs, chlorpromazine, alpha-flupenthixol, haloperidol and spiroperidol block both syndromes. The inhibition produced by these drugs on 5-HT-induced hyperactivity is probably because a dopaminergic system is involved in the behavioural expression of the 5-HT induced hyperactivity. The structurally related drugs with no neuroleptic activity (ethopropazine, promethazine and beta-flupenthixol)are without effect on thses hyperactivity syndromes. Also ineffective were the neuroleptics pimozide and clozapine. Striatal dopamine sensitive adenylate cyclase activity in vitro was inhibited by the administration of chlorpromazine (100 mg/kg) in vivo. Rats treated for 4 or more days with chlorpromazine, alpha-flupenthixol, spiroperidol and haloperidol subsequently showed enhanced locomotor activity in response to tranylcypromine and L-Dopa. Administration of those drugs which did not block hyperactivity acutely did not result in enhancement. Only chlorpromazine, when given for 4 days, enhanced the hyperactivity response following tranylcypromine and L-tryptophan, probably because the drug also blocks 5-HT receptors. In rats displaying enhanced behavioural responses no evidence was found for enhanced sensitivity of striatal adenylate cyclase to dopamine."}
{"id": "PMID:12528", "title": "Effects of pyrroxan and chlordiazepoxide on biogenic amine metabolism in the rat brain.", "content": "Pyrroxan (20 mg/kg, i.p.), a new potential antianxiety agent, increased brain norepinephrine (NE) turnover in rats, reflecting a possible central alpha-adrenergic receptor blocking activity. In contrast, chlordiazepoxide (20 mg/kg, i.p.), a widely used antianxiety agent, did not alter the NE turnover. Pyrroxan did not affect overall DA turnover although it did appear to accelerate DA turnover initially. The initial potentiation of DA turnover may indicate a short-lasting blocking action on DA receptors. In comparison, chlordiazepoxide (20 mg/kg, i.p.) decreased the turnover rate of DA. Effects of both drugs on 5-HT indicate a decrease in turnover with no significant monoamine oxidase activity or blockade of the 5-HT reuptake mechanism. Both drugs antagonized the decline in intraventicularly-injected 14C-5-HT. Neither drug caused consistent changes in endogenous 5-HT, 5-hydroxyindoleacetic acid, or tryptophan levels. Neither drug potentiated the behavioral effects of L-Dopa nor increased the 5-HTP behavoiral syndrome in the mouse. Pyrroxan may be expected to exhibit a spectrum of activity between that of minor and major tranquilizers, characterized by antianxiety action together with sedative or tranquilizing activity.", "contents": "Effects of pyrroxan and chlordiazepoxide on biogenic amine metabolism in the rat brain. Pyrroxan (20 mg/kg, i.p.), a new potential antianxiety agent, increased brain norepinephrine (NE) turnover in rats, reflecting a possible central alpha-adrenergic receptor blocking activity. In contrast, chlordiazepoxide (20 mg/kg, i.p.), a widely used antianxiety agent, did not alter the NE turnover. Pyrroxan did not affect overall DA turnover although it did appear to accelerate DA turnover initially. The initial potentiation of DA turnover may indicate a short-lasting blocking action on DA receptors. In comparison, chlordiazepoxide (20 mg/kg, i.p.) decreased the turnover rate of DA. Effects of both drugs on 5-HT indicate a decrease in turnover with no significant monoamine oxidase activity or blockade of the 5-HT reuptake mechanism. Both drugs antagonized the decline in intraventicularly-injected 14C-5-HT. Neither drug caused consistent changes in endogenous 5-HT, 5-hydroxyindoleacetic acid, or tryptophan levels. Neither drug potentiated the behavioral effects of L-Dopa nor increased the 5-HTP behavoiral syndrome in the mouse. Pyrroxan may be expected to exhibit a spectrum of activity between that of minor and major tranquilizers, characterized by antianxiety action together with sedative or tranquilizing activity."}
{"id": "PMID:12529", "title": "Investigations of the mechanism of central action of kinins.", "content": "The effects of kinins on the level of norepinephrine, dopamine, and serotonin and on their metabolites, i.e., normetanephrine, homovanillic acid, and 5-hydroxyindoloacetic acid in the brain tissue divided into cerebellum, corpus striatum, cortex, hippocampus, hypothalamus, medulla oblongata, and midbrain were investigated. It was shown that bradykinin in a dose of 4 mug decreased the content of norepinephrine in corpus striatum, midbrain, and cerebellum. It also decreased the level of dopamine in corpus striatum but increased the level of serotonin in corpus striatum and midbrain. Similar changes were observed with 100 Mu/kg of kallikrein. It was that changed levels of investigated neuromediators are accompanied by changed levels of their metabolites. Bradykinin, in a dose of 4 mug, decreased the level of normetanephrine in corpus striatum, hippocampus, and midbrain and the level of homovanillic acid in corpus striatum, and increased the level of 5-hydroxyindoloacetic acid in corpus striatum and hippocampus. It was also shown that bradykinin increased norepinephrine uptake by the blood platelets when its level in the platelets was low, and released the absorbed norepinephrine into the medium when the level of norepinephrine was higher. The above results confirm the existence of an interaction of kinins with neuromediators in the central nervous system.", "contents": "Investigations of the mechanism of central action of kinins. The effects of kinins on the level of norepinephrine, dopamine, and serotonin and on their metabolites, i.e., normetanephrine, homovanillic acid, and 5-hydroxyindoloacetic acid in the brain tissue divided into cerebellum, corpus striatum, cortex, hippocampus, hypothalamus, medulla oblongata, and midbrain were investigated. It was shown that bradykinin in a dose of 4 mug decreased the content of norepinephrine in corpus striatum, midbrain, and cerebellum. It also decreased the level of dopamine in corpus striatum but increased the level of serotonin in corpus striatum and midbrain. Similar changes were observed with 100 Mu/kg of kallikrein. It was that changed levels of investigated neuromediators are accompanied by changed levels of their metabolites. Bradykinin, in a dose of 4 mug, decreased the level of normetanephrine in corpus striatum, hippocampus, and midbrain and the level of homovanillic acid in corpus striatum, and increased the level of 5-hydroxyindoloacetic acid in corpus striatum and hippocampus. It was also shown that bradykinin increased norepinephrine uptake by the blood platelets when its level in the platelets was low, and released the absorbed norepinephrine into the medium when the level of norepinephrine was higher. The above results confirm the existence of an interaction of kinins with neuromediators in the central nervous system."}
{"id": "PMID:12530", "title": "Sleep disorder and psychobiological symptomatology in male psychiatric outpatients and male nonpatients.", "content": "Sleep disturbance was studied in relation to psychiatric and physical symptoms for 214 male psychiatric outpatients and 248 male nonpatients. Our self-report instrument required that subjects describe the frequency of symptoms precisely on a five-point scale from \"every day\" to \"not at all.\" Percentages are based on the numbers of subjects reporting a symptom as occurring \"every day\" or \"several times a week.\" More patients reported sleep disturbance symptoms (75%) than nonpatients (25%) (P less than 0.001). Sleep loss symptoms were reported by 63% of patients and 20% of nonpatients. Twelve percent of patients and 6% of nonpatients reported trouble with excessive sleep problems. Sleep disturbance was not strongly related to specific diagnoses. Fewer schizophrenics (21%) than other patients (50%) reported trouble \"falling asleep\" (P less than 0.02). Finally, for both patients and controls, disturbed sleepers reported more psychiatric and physical symptoms than undisturbed sleepers (P less than 0.001). It is suggested that sleep disturbance might be a useful clinical clue to previously unsuspected psychiatric and physical illness.", "contents": "Sleep disorder and psychobiological symptomatology in male psychiatric outpatients and male nonpatients. Sleep disturbance was studied in relation to psychiatric and physical symptoms for 214 male psychiatric outpatients and 248 male nonpatients. Our self-report instrument required that subjects describe the frequency of symptoms precisely on a five-point scale from \"every day\" to \"not at all.\" Percentages are based on the numbers of subjects reporting a symptom as occurring \"every day\" or \"several times a week.\" More patients reported sleep disturbance symptoms (75%) than nonpatients (25%) (P less than 0.001). Sleep loss symptoms were reported by 63% of patients and 20% of nonpatients. Twelve percent of patients and 6% of nonpatients reported trouble with excessive sleep problems. Sleep disturbance was not strongly related to specific diagnoses. Fewer schizophrenics (21%) than other patients (50%) reported trouble \"falling asleep\" (P less than 0.02). Finally, for both patients and controls, disturbed sleepers reported more psychiatric and physical symptoms than undisturbed sleepers (P less than 0.001). It is suggested that sleep disturbance might be a useful clinical clue to previously unsuspected psychiatric and physical illness."}
{"id": "PMID:12535", "title": "Intraperitoneal and retroperitoneal hemorrhage.", "content": "Besides blunt and penetrating trauma, many diseases spontaneously produce abdominal hemorrhage. Here the term \"spontaneous\" implies the lack of observable injury, but the likelihood that unrecognized trauma initiates blood loss which continues unabated when clotting factors are absent or depleted. Survival of the patient often depends on rapid and accurate diagnosis.", "contents": "Intraperitoneal and retroperitoneal hemorrhage. Besides blunt and penetrating trauma, many diseases spontaneously produce abdominal hemorrhage. Here the term \"spontaneous\" implies the lack of observable injury, but the likelihood that unrecognized trauma initiates blood loss which continues unabated when clotting factors are absent or depleted. Survival of the patient often depends on rapid and accurate diagnosis."}
{"id": "PMID:12531", "title": "Stages of bone marrow transplantation: a psychiatric perspective.", "content": "Patients undergoing bone marrow transplantation were closely followed by a psychiatric service functioning as part of a multidisciplinary team. A somewhat predictable pattern of psychological reactions to the stress of various stages of the procedure appeared to emerge. Approaches to patient evaluation, typical patient responses, and suggestions for working with these patients and their families are described.", "contents": "Stages of bone marrow transplantation: a psychiatric perspective. Patients undergoing bone marrow transplantation were closely followed by a psychiatric service functioning as part of a multidisciplinary team. A somewhat predictable pattern of psychological reactions to the stress of various stages of the procedure appeared to emerge. Approaches to patient evaluation, typical patient responses, and suggestions for working with these patients and their families are described."}
{"id": "PMID:12538", "title": "The chemical structure of prostaglandin X (prostacyclin).", "content": "The chemical structure of prostaglandin X, the anti-aggregatory substance derived from prostaglandin endoperoxides, is 9-deoxy-6, 6alpha-epoxy-delta5-PGF1alpha. The stable compound formed when prostaglandin X undergoes a chemical transformation in biological systems in 6-keto-PGF1alpha. Prostaglandin X is stabilized in aqueous preparations by raising the pH to 8.5 or higher. The trivial name prostacyclin is proposed for 9-deoxy-6, 9alpha-epoxy-delta5-PGF1alpha.", "contents": "The chemical structure of prostaglandin X (prostacyclin). The chemical structure of prostaglandin X, the anti-aggregatory substance derived from prostaglandin endoperoxides, is 9-deoxy-6, 6alpha-epoxy-delta5-PGF1alpha. The stable compound formed when prostaglandin X undergoes a chemical transformation in biological systems in 6-keto-PGF1alpha. Prostaglandin X is stabilized in aqueous preparations by raising the pH to 8.5 or higher. The trivial name prostacyclin is proposed for 9-deoxy-6, 9alpha-epoxy-delta5-PGF1alpha."}
{"id": "PMID:12539", "title": "Biosynthesis of thromboxane B2: assay, isolation, and properties of the enzyme system in human platelets.", "content": "The microsomal fraction of human platelets catalyzed the conversion of arachidonic acid to an unstable platelet-aggregating factor and a hydrolyzed product on the thin-layer chromatography (TLC). This product was isolated on TLC, purified by silica gel column chromatography and identified by combined gas chromatography-mass spectrometry as the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5, 10-heptadecatrienoic acid (thromboxane B2). The enzymatic activity was dependent upon methemoglobin and tryptophan as cofactors. Reduced glutathione had no effect either alone or in combination with other cofactors. Methemoglobin could be replaced by hematin or hemin; and tryptophan by 3-indolacetic acid or catecholamines. The apparent requirement for methemoglobin is due to the reductive activity of ferriprotoporphyrin IX. The reaction, however, catalyzed by the ferriprotoporphyrin IX in the thromboxane synthesizing system is different from that described for the decomposition of lipid peroxides. Certain transition metals and hydrogen donors, such as hydroquinone and ascorbate, which have been shown to stimulate the catalytic activity of ferriproroporphyrin IX in the decomposition of 15-hydroperoxy-prostaglandin E1 are inhibitors of thromboxane B2 formation. This enzyme preparation also transformed eicosa-8. 11, 14-trienoic acid to an unknown product on TLC. The enzyme system was rapidly inactivated upon incubation in the reaction mixture.", "contents": "Biosynthesis of thromboxane B2: assay, isolation, and properties of the enzyme system in human platelets. The microsomal fraction of human platelets catalyzed the conversion of arachidonic acid to an unstable platelet-aggregating factor and a hydrolyzed product on the thin-layer chromatography (TLC). This product was isolated on TLC, purified by silica gel column chromatography and identified by combined gas chromatography-mass spectrometry as the hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5, 10-heptadecatrienoic acid (thromboxane B2). The enzymatic activity was dependent upon methemoglobin and tryptophan as cofactors. Reduced glutathione had no effect either alone or in combination with other cofactors. Methemoglobin could be replaced by hematin or hemin; and tryptophan by 3-indolacetic acid or catecholamines. The apparent requirement for methemoglobin is due to the reductive activity of ferriprotoporphyrin IX. The reaction, however, catalyzed by the ferriprotoporphyrin IX in the thromboxane synthesizing system is different from that described for the decomposition of lipid peroxides. Certain transition metals and hydrogen donors, such as hydroquinone and ascorbate, which have been shown to stimulate the catalytic activity of ferriproroporphyrin IX in the decomposition of 15-hydroperoxy-prostaglandin E1 are inhibitors of thromboxane B2 formation. This enzyme preparation also transformed eicosa-8. 11, 14-trienoic acid to an unknown product on TLC. The enzyme system was rapidly inactivated upon incubation in the reaction mixture."}
{"id": "PMID:12543", "title": "[Effect of the ionic environment and of various neurotransmitters on spontaneous motility in snail intestine (author's transl)].", "content": "A spontaneous rhythmic motility of the isolated intestine in snail, Chryptomphalus hortensis, has been registered at 30 degrees C with the aid of an electronic transductor and an appropriate amplification. These slow regular movements are affected by ionic composition changes in the suspension medium. Na+, K+ and Ca++ ions prove to be important in this motility, and the addition of Ba++ markedly stimulates it. ACh produces hypermotility from 1.8 X 10(-11) g/ml. Its effect decreases in the presence of atropine and increases in that of pyridostigmine. The intestine is sensitive to 5-HT from 10(-10) g/ml, which stimulates its activity. The effect of histamine is weak. Low concentrations of adrenaline tend to increase the amplitude, whereas concentrations from 10(-5) g/ml onward produce a cease of motility in relaxation.", "contents": "[Effect of the ionic environment and of various neurotransmitters on spontaneous motility in snail intestine (author's transl)]. A spontaneous rhythmic motility of the isolated intestine in snail, Chryptomphalus hortensis, has been registered at 30 degrees C with the aid of an electronic transductor and an appropriate amplification. These slow regular movements are affected by ionic composition changes in the suspension medium. Na+, K+ and Ca++ ions prove to be important in this motility, and the addition of Ba++ markedly stimulates it. ACh produces hypermotility from 1.8 X 10(-11) g/ml. Its effect decreases in the presence of atropine and increases in that of pyridostigmine. The intestine is sensitive to 5-HT from 10(-10) g/ml, which stimulates its activity. The effect of histamine is weak. Low concentrations of adrenaline tend to increase the amplitude, whereas concentrations from 10(-5) g/ml onward produce a cease of motility in relaxation."}
{"id": "PMID:12544", "title": "Participation of leukemia cells in immune responses.", "content": "Cells of a transplantable lymphoid leukemia of mice were tested in vivo and in vitro to see which features of normal lymphoid cells were retained in spite of malignant transformation and lack of growth control. Leukemia cells phagocytosed, adhered to glass, possessed receptors for immunoglobulin, participated in the immune response against SRBC (probably by amplifying a normal response through attachement of antibodies on their surfaces), became recruited into inflammatory reactions elicited by grafting allogeneic of syngeneic skin, and apparently joined graft-versus-host and host-versus-graft reactions, contributing toward damage of hemopoietic target tissues.", "contents": "Participation of leukemia cells in immune responses. Cells of a transplantable lymphoid leukemia of mice were tested in vivo and in vitro to see which features of normal lymphoid cells were retained in spite of malignant transformation and lack of growth control. Leukemia cells phagocytosed, adhered to glass, possessed receptors for immunoglobulin, participated in the immune response against SRBC (probably by amplifying a normal response through attachement of antibodies on their surfaces), became recruited into inflammatory reactions elicited by grafting allogeneic of syngeneic skin, and apparently joined graft-versus-host and host-versus-graft reactions, contributing toward damage of hemopoietic target tissues."}
{"id": "PMID:12542", "title": "[The concept of risk in parasitic diseases with special reference to malaria (author's transl)].", "content": "The concept of risk, its components and their interrelationship are described. Emphasis has been placed on the value of the variables to be taken into account in the selection of intervention measures: -- for the mosquito: the daily frequency of blood meals taken from man, the duration of the sporogonic cycle, the daily survival rate and the proportion of people with gametocytes in the peripheral blood; -- for man: the number of anophelines feeding on man in a unit of time, the proportion of mosquitoes with sporozo\u00eftes in their salivary glands and the proportion of sporozo\u00eftes able to infect man. Using these variables, it is possible to calculate the various risks incurred both by man and vector. Whenever possible and in order to be of greater value, the interventions should be directed against the variable which have the highest power. However, in view of the complexity of relations, it is better to construct a mathematical model able to simulate with the use of a computer, real epidemiological situations. A model has been recently developed for the study of the malaria dynamics and for the comparative evaluation of various methods of control.", "contents": "[The concept of risk in parasitic diseases with special reference to malaria (author's transl)]. The concept of risk, its components and their interrelationship are described. Emphasis has been placed on the value of the variables to be taken into account in the selection of intervention measures: -- for the mosquito: the daily frequency of blood meals taken from man, the duration of the sporogonic cycle, the daily survival rate and the proportion of people with gametocytes in the peripheral blood; -- for man: the number of anophelines feeding on man in a unit of time, the proportion of mosquitoes with sporozo\u00eftes in their salivary glands and the proportion of sporozo\u00eftes able to infect man. Using these variables, it is possible to calculate the various risks incurred both by man and vector. Whenever possible and in order to be of greater value, the interventions should be directed against the variable which have the highest power. However, in view of the complexity of relations, it is better to construct a mathematical model able to simulate with the use of a computer, real epidemiological situations. A model has been recently developed for the study of the malaria dynamics and for the comparative evaluation of various methods of control."}
{"id": "PMID:12548", "title": "Antagonism by naloxone of morphine-induced single-dose dependence and antinociception in mice.", "content": "Single-dose physical dependence on morphine, as indicated by the mouse withdrawal jumping test, was reduced in a dose-related fashion by co-administration of naloxone. In the same dose range, naloxone also antagonized the antinociceptive effect of morphine in the mouse writhing test. Dose-response data revealed essentially the same ED50's for naloxone in both tests. These results indicate that naloxone does indeed block the development of morphine-induced single-dose physical dependence in mice and that it does so as effectively as it blocks morphine-induced inhibition of writhing.", "contents": "Antagonism by naloxone of morphine-induced single-dose dependence and antinociception in mice. Single-dose physical dependence on morphine, as indicated by the mouse withdrawal jumping test, was reduced in a dose-related fashion by co-administration of naloxone. In the same dose range, naloxone also antagonized the antinociceptive effect of morphine in the mouse writhing test. Dose-response data revealed essentially the same ED50's for naloxone in both tests. These results indicate that naloxone does indeed block the development of morphine-induced single-dose physical dependence in mice and that it does so as effectively as it blocks morphine-induced inhibition of writhing."}
{"id": "PMID:12549", "title": "Changes in brain catecholamines and spontaneous locomotor activity in response to thyrotropin releasing hormone.", "content": "Repeated exposure of rats to thyrotropin releasing hormone produced a dose- and time-dependent increase in spontaneous locomotor activity accompanied by an increase in brain stem tyrosine hydroxylase. Dopamine levels in cerebral cortex were increased maximally by 34% in animals receiving thyrotropin releasing hormone at a dosage of 2 mg/kg for 10 days. The concentrations of brain stem tyrosine and cerebral cortex norepinephrine remained unaltered in response  to thyrotropin releasing hormone treatment. Our data suggest that administration of thyrotropin releasing hormone increases the synthesis and perhaps the turnover of brain catecholamines and that this may constitute an underlying mechanism for the anti-depressant action of this synthetic hormone.", "contents": "Changes in brain catecholamines and spontaneous locomotor activity in response to thyrotropin releasing hormone. Repeated exposure of rats to thyrotropin releasing hormone produced a dose- and time-dependent increase in spontaneous locomotor activity accompanied by an increase in brain stem tyrosine hydroxylase. Dopamine levels in cerebral cortex were increased maximally by 34% in animals receiving thyrotropin releasing hormone at a dosage of 2 mg/kg for 10 days. The concentrations of brain stem tyrosine and cerebral cortex norepinephrine remained unaltered in response  to thyrotropin releasing hormone treatment. Our data suggest that administration of thyrotropin releasing hormone increases the synthesis and perhaps the turnover of brain catecholamines and that this may constitute an underlying mechanism for the anti-depressant action of this synthetic hormone."}
{"id": "PMID:12551", "title": "Vasomotor rhinitis: psychosomatic conditions and treatment.", "content": "The importance of the autonomic nervous system in vasomotor conditions of the nose was outlined. The symptoms, findings and differential diagnosis of the vasomator rhinitis were reviewed. Reference is made to the applied treatment and results obtained with different antistaminics in 2150 patients.", "contents": "Vasomotor rhinitis: psychosomatic conditions and treatment. The importance of the autonomic nervous system in vasomotor conditions of the nose was outlined. The symptoms, findings and differential diagnosis of the vasomator rhinitis were reviewed. Reference is made to the applied treatment and results obtained with different antistaminics in 2150 patients."}
{"id": "PMID:12554", "title": "Improvement in the quality of enzyme determinations by Scandinavian laboratories upon introduction of Scandinavian recommended methods.", "content": "The last annual Scandinavian proficiency survey (January 1975) offered an opportunity to evaluate the effect of the introduction of recommended methods for ASAT, ALAT, LD, and ALP on routinely performed enzyme determinations in clinical chemical laboratories. The results obtained by the recommended methods showed a marked improvement in precision, bringing the interlaboratory variations down to levels that have previously been achieved only for the determination of non-enzymic constituents. Enzymes for which no recommended method have been proposed were still determined with low interlaboratory precision.", "contents": "Improvement in the quality of enzyme determinations by Scandinavian laboratories upon introduction of Scandinavian recommended methods. The last annual Scandinavian proficiency survey (January 1975) offered an opportunity to evaluate the effect of the introduction of recommended methods for ASAT, ALAT, LD, and ALP on routinely performed enzyme determinations in clinical chemical laboratories. The results obtained by the recommended methods showed a marked improvement in precision, bringing the interlaboratory variations down to levels that have previously been achieved only for the determination of non-enzymic constituents. Enzymes for which no recommended method have been proposed were still determined with low interlaboratory precision."}
{"id": "PMID:12555", "title": "A method for enzymatic determination of citrate in serum and urine.", "content": "A method for determination of citrate in serum and urine using citrate lyase is described. The influence of pH, zinc, magnesium, and calcium ions on the reaction velocity is studied. Citrate lyase activity is found rather insensitive to variations in pH round the pH-optimum at 8.2. Zinc ions activate the reactions. The optimal concentration of zinc ions in the reaction mixture is found to depend on the calcium concentration of samples. Perchloric acid is used for precipitation of proteins. The perchloric ion inhibits the reaction,  and a procedure for removing perchlorate is given. Sensitivity of analysis is  0.005 mmo1/1 for serum and urine samples, respectively. No contamination of citrate lyase is found, and therefore addition of lactate dehydrogenase is considered unneccessary.", "contents": "A method for enzymatic determination of citrate in serum and urine. A method for determination of citrate in serum and urine using citrate lyase is described. The influence of pH, zinc, magnesium, and calcium ions on the reaction velocity is studied. Citrate lyase activity is found rather insensitive to variations in pH round the pH-optimum at 8.2. Zinc ions activate the reactions. The optimal concentration of zinc ions in the reaction mixture is found to depend on the calcium concentration of samples. Perchloric acid is used for precipitation of proteins. The perchloric ion inhibits the reaction,  and a procedure for removing perchlorate is given. Sensitivity of analysis is  0.005 mmo1/1 for serum and urine samples, respectively. No contamination of citrate lyase is found, and therefore addition of lactate dehydrogenase is considered unneccessary."}
{"id": "PMID:12552", "title": "Clinical assessment of cryptorchid boys by determination of urinary testosterone glucuronide following large doses of human chorionic gonadotropin (hCG).", "content": "Urinary TG and fractionated 17-ketosteroid (Drosdowsky) determinations were performed before and after the intramuscular administration of 15,000 IU of human chorionic gonadotropin (hCG) in 10 sexually immature healthy boys and in 12 bilaterally cryptorchid boys. The same basal determinations were made in 11 gonadless girls. Basal serum FSH and LH were determined (by radioimmunoassay) in controls and also in cryptorchid boys. If 15mug/24 h (three SD's of basal excretion in controls) is considered the smallest adequate response, the TG but not the fractionated 17-KS determination assessed fairly well either the presence or the functional capacity of the Leydig cell-containing tissue. Agonadic girls had significantly higher basal excretion of steroids and this is presumably due to their greater absolute body size and to their more advanced bone age.", "contents": "Clinical assessment of cryptorchid boys by determination of urinary testosterone glucuronide following large doses of human chorionic gonadotropin (hCG). Urinary TG and fractionated 17-ketosteroid (Drosdowsky) determinations were performed before and after the intramuscular administration of 15,000 IU of human chorionic gonadotropin (hCG) in 10 sexually immature healthy boys and in 12 bilaterally cryptorchid boys. The same basal determinations were made in 11 gonadless girls. Basal serum FSH and LH were determined (by radioimmunoassay) in controls and also in cryptorchid boys. If 15mug/24 h (three SD's of basal excretion in controls) is considered the smallest adequate response, the TG but not the fractionated 17-KS determination assessed fairly well either the presence or the functional capacity of the Leydig cell-containing tissue. Agonadic girls had significantly higher basal excretion of steroids and this is presumably due to their greater absolute body size and to their more advanced bone age."}
{"id": "PMID:12556", "title": "Transferrin and iron uptake by isolated rat liver mitochondria.", "content": "Isolated rat liver mitochondria accumulate iron from the suspending medium when [59Fe]transferrin is used as a model compound. The accumulation proceeds by two different mechanisms, i.e. by an energy-independent and an energy-dependent (uncoupler sensitive) mechanism, which have different time, pH, and temperature dependencies. The energy-dependent accumulation, which is inhibited by ruthenium red and sulphydryl reagents, reaches a saturation level of approx. 30 pmoles iron/mg protein during 30 min incubation. The energy-independent accumulation of iron-transferrin reveals no saturation kinetics, it is inhibited neither by ruthenium red nor by N-ethylmaleimide, and it proceeds linearly for at least 90 min. With [125I]transferrin as a model compound, quantitatively the energy-independent accumulation is as reported for [59Fe]transferrin. There is, however, no energy-dependent accumulation of [125I]transferrin. The results indicate that the energy-dependent accumulation of [59Fe]transferrin represents a process by which mitochondria accumulate iron from transferrin.", "contents": "Transferrin and iron uptake by isolated rat liver mitochondria. Isolated rat liver mitochondria accumulate iron from the suspending medium when [59Fe]transferrin is used as a model compound. The accumulation proceeds by two different mechanisms, i.e. by an energy-independent and an energy-dependent (uncoupler sensitive) mechanism, which have different time, pH, and temperature dependencies. The energy-dependent accumulation, which is inhibited by ruthenium red and sulphydryl reagents, reaches a saturation level of approx. 30 pmoles iron/mg protein during 30 min incubation. The energy-independent accumulation of iron-transferrin reveals no saturation kinetics, it is inhibited neither by ruthenium red nor by N-ethylmaleimide, and it proceeds linearly for at least 90 min. With [125I]transferrin as a model compound, quantitatively the energy-independent accumulation is as reported for [59Fe]transferrin. There is, however, no energy-dependent accumulation of [125I]transferrin. The results indicate that the energy-dependent accumulation of [59Fe]transferrin represents a process by which mitochondria accumulate iron from transferrin."}
{"id": "PMID:12553", "title": "[Use of a monomaxillary curved splint in maxillofacial surgery].", "content": "We describe a prefabricated monomaxillary arch, fitted with perpendicular supports with a main bar which provides dento-maxillary setting in the antero-posterior direction and also vertically since it is possible to attach it to the free edge of the teeth. The indications concerning the use of this arch are given in detail. It offers the advantage of being readily adaptable and is therefore easy to use in an emergency.", "contents": "[Use of a monomaxillary curved splint in maxillofacial surgery]. We describe a prefabricated monomaxillary arch, fitted with perpendicular supports with a main bar which provides dento-maxillary setting in the antero-posterior direction and also vertically since it is possible to attach it to the free edge of the teeth. The indications concerning the use of this arch are given in detail. It offers the advantage of being readily adaptable and is therefore easy to use in an emergency."}
{"id": "PMID:12557", "title": "Microcalorimetric measurements of heat production in human erythrocytes. III. Influence of pH, temperature, glucose concentration, and storage conditions.", "content": "Heat production in human erythrocytes has been measured under different conditions of pH, glucose concentration, and temperature. Storage conditions have also been varied. The erythrocytes, which were from healthy subjects, were suspended either in autologous plasma or in phosphate buffer. The heat effect, P, was shown to increase linearly in the physiological pH range: 1.2% per 0.01 pH unit. Variation of the glucose concentration within a wide range, 3-32 mmol/1, did not affect the P value. The temperature coefficient for P was determined to be Q10 = 2.8 for the temperature range 32-42 degrees C. A constant energy of activation was found, 82.6 kJ/mol, for the temperature range 25-42 degrees C. When the erythrocytes were stored at 4 degrees C, P values (measured at 37 degrees C) increased initially by 6%/h. After 24 h of storage P was about 50% higher than the initial value. Determinations of glucose consumption were made in parallel with most of the calorimetric experiments.", "contents": "Microcalorimetric measurements of heat production in human erythrocytes. III. Influence of pH, temperature, glucose concentration, and storage conditions. Heat production in human erythrocytes has been measured under different conditions of pH, glucose concentration, and temperature. Storage conditions have also been varied. The erythrocytes, which were from healthy subjects, were suspended either in autologous plasma or in phosphate buffer. The heat effect, P, was shown to increase linearly in the physiological pH range: 1.2% per 0.01 pH unit. Variation of the glucose concentration within a wide range, 3-32 mmol/1, did not affect the P value. The temperature coefficient for P was determined to be Q10 = 2.8 for the temperature range 32-42 degrees C. A constant energy of activation was found, 82.6 kJ/mol, for the temperature range 25-42 degrees C. When the erythrocytes were stored at 4 degrees C, P values (measured at 37 degrees C) increased initially by 6%/h. After 24 h of storage P was about 50% higher than the initial value. Determinations of glucose consumption were made in parallel with most of the calorimetric experiments."}
{"id": "PMID:12558", "title": "The absorption of acetylsalicylic acid from the stomach in relation to intragastric pH.", "content": "A comparative study on the effect of a buffered (pH 6.5) and an unbuffered (pH 2.9) solution of acetylsalicylic acid (ASA) on gastric pH, gastric emptying, and gastric absorption of ASA was performed in 10 healthy volunteers. Gastric pH was recorded using radiotelemetry. Gastric emptying and gastric absorption was studied with an aspiration technique and phenol red as nonabsorbable marker. Administration of the unbuffered solution to the fasting subjects resulted in a gastric pH of about 2 and absorption of ASA from the stomach was found to occur. The buffered solution of ASA increased gastric pH to above 5 and gastric absorption of ASA was found to be significantly less than after the unbuffered solution. The buffered solution was emptied from the stomach more rapidly than the unbuffered one.", "contents": "The absorption of acetylsalicylic acid from the stomach in relation to intragastric pH. A comparative study on the effect of a buffered (pH 6.5) and an unbuffered (pH 2.9) solution of acetylsalicylic acid (ASA) on gastric pH, gastric emptying, and gastric absorption of ASA was performed in 10 healthy volunteers. Gastric pH was recorded using radiotelemetry. Gastric emptying and gastric absorption was studied with an aspiration technique and phenol red as nonabsorbable marker. Administration of the unbuffered solution to the fasting subjects resulted in a gastric pH of about 2 and absorption of ASA from the stomach was found to occur. The buffered solution of ASA increased gastric pH to above 5 and gastric absorption of ASA was found to be significantly less than after the unbuffered solution. The buffered solution was emptied from the stomach more rapidly than the unbuffered one."}
{"id": "PMID:12561", "title": "[Endocrinological studies in arterial hypertension. Search for phaeochromocytoma].", "content": "Elevated urinary catecholamines and their metabolites are the only findings which confirm the presence of pheochromocytoma. This examination is of particular interest if carried out in urine produced after spontaneous hypertensive episodes. Pharmacologic tests when carried out under standard conditions have proven to be a reliable aid in cases of suspected pheochromocytoma. Roentgenographic studies, determination of local plasma catecholamine concentrations and blood volume control should be undertaken in these patients before surgical procedure.", "contents": "[Endocrinological studies in arterial hypertension. Search for phaeochromocytoma]. Elevated urinary catecholamines and their metabolites are the only findings which confirm the presence of pheochromocytoma. This examination is of particular interest if carried out in urine produced after spontaneous hypertensive episodes. Pharmacologic tests when carried out under standard conditions have proven to be a reliable aid in cases of suspected pheochromocytoma. Roentgenographic studies, determination of local plasma catecholamine concentrations and blood volume control should be undertaken in these patients before surgical procedure."}
{"id": "PMID:12562", "title": "[Paralytic ileus in pheochromocytoma. Possible correlation with an attempt at adrenal phlebography].", "content": "Following adrenal phlebography, obstruction of the large bowel associated with adrenergic crisis was observed in a 60 year old patient with pheochromocytoma. As in other published cases of ileus associated with pheochromocytoma, high urinary catecholamine concentrations were found in our patient and the tumor resected at surgery was large. As phlebography immediately preceded the onset of ileus and hypertensive crisis, it is postulated that angiography led to massive secretion of catecholamines, which caused the hypertensive crisis as well as the ileus. The possible mechanisms by which phlebography may lead to adrenergic crisis are discussed. It is concluded that in suspected pheochromocytoma all angiographic examinations should be carried out under simultaneous treatment with alpha-blocking agents.", "contents": "[Paralytic ileus in pheochromocytoma. Possible correlation with an attempt at adrenal phlebography]. Following adrenal phlebography, obstruction of the large bowel associated with adrenergic crisis was observed in a 60 year old patient with pheochromocytoma. As in other published cases of ileus associated with pheochromocytoma, high urinary catecholamine concentrations were found in our patient and the tumor resected at surgery was large. As phlebography immediately preceded the onset of ileus and hypertensive crisis, it is postulated that angiography led to massive secretion of catecholamines, which caused the hypertensive crisis as well as the ileus. The possible mechanisms by which phlebography may lead to adrenergic crisis are discussed. It is concluded that in suspected pheochromocytoma all angiographic examinations should be carried out under simultaneous treatment with alpha-blocking agents."}
{"id": "PMID:12563", "title": "[Pharmacokinetics of two beta blocking drugs: detection of a pharmacogenetic abnormality].", "content": "10 healthy male volunteers received orally either 100 mg tolamolol or 20 mg bufuralol. These experiments were repeated by intravenous administration of 10 and 5 mg respectively of these two drugs. Plasma levels of the parent drugs and their main metabolite were measured. In one subject, the apparent half-life of elimination was increased from 2.5 h (normal subjects) to 5 h for both drugs. This prolongation of the half-life is associated with low plasma levels of the metabolites, a peculiarity which can be explanined by a decreased rate of metabolism for these two drugs. This anomaly may explain the marked orthostatic hypotension observed only in this subject. The likelihood of a pharmacogenetic defect is discussed.", "contents": "[Pharmacokinetics of two beta blocking drugs: detection of a pharmacogenetic abnormality]. 10 healthy male volunteers received orally either 100 mg tolamolol or 20 mg bufuralol. These experiments were repeated by intravenous administration of 10 and 5 mg respectively of these two drugs. Plasma levels of the parent drugs and their main metabolite were measured. In one subject, the apparent half-life of elimination was increased from 2.5 h (normal subjects) to 5 h for both drugs. This prolongation of the half-life is associated with low plasma levels of the metabolites, a peculiarity which can be explanined by a decreased rate of metabolism for these two drugs. This anomaly may explain the marked orthostatic hypotension observed only in this subject. The likelihood of a pharmacogenetic defect is discussed."}
{"id": "PMID:12564", "title": "[Contribution to the treatment of threatened abortion].", "content": "460 cases of threatened abortion were divided into 3 different treatment categories. Group A was treated with a combined antihistamine and antispasmodic, and Group B with tranquilizers and synthetic gestagens. Group C consisted of patients who refused therapy. The percentage of delayed abortions in group A was 79.3%, in group B 84.7% and in group C 54.8%. According to the x2-test, the difference between the treated and untreated groups is statistically significant. The mode of action of the prescribed drugs is substantiated and their effectiveness was compared with published data on other therapies. Complications of pregnancy, at delivery and during the puerperium were not more prevalent than in normal pregnancies. However, the percentage of premature births (22.9%) and of perinatal mortality (5.4%) was strikingly high. Accordingly, successfully treated threatened abortions are to be followed up as \"risk\" pregnancies and closely supervised as such. It is especially important to avoid a premature birth. The frequency of congenital defects and functional disturbances was 11.9%; their existence is independent of the type of therapy. Since the defects are usually of minor consequence and reversible, we advocate treatment of the threatened abortion.", "contents": "[Contribution to the treatment of threatened abortion]. 460 cases of threatened abortion were divided into 3 different treatment categories. Group A was treated with a combined antihistamine and antispasmodic, and Group B with tranquilizers and synthetic gestagens. Group C consisted of patients who refused therapy. The percentage of delayed abortions in group A was 79.3%, in group B 84.7% and in group C 54.8%. According to the x2-test, the difference between the treated and untreated groups is statistically significant. The mode of action of the prescribed drugs is substantiated and their effectiveness was compared with published data on other therapies. Complications of pregnancy, at delivery and during the puerperium were not more prevalent than in normal pregnancies. However, the percentage of premature births (22.9%) and of perinatal mortality (5.4%) was strikingly high. Accordingly, successfully treated threatened abortions are to be followed up as \"risk\" pregnancies and closely supervised as such. It is especially important to avoid a premature birth. The frequency of congenital defects and functional disturbances was 11.9%; their existence is independent of the type of therapy. Since the defects are usually of minor consequence and reversible, we advocate treatment of the threatened abortion."}
{"id": "PMID:12565", "title": "Lysogeny in pneumococci freshly isolated from man.", "content": "Twelve strains of encapsulated pneumococci isolated from patients with pneumococcal disease were examined for the presence of bacteriophage. Four of the strains yielded phage lytic for a noncapsulated indicator strain of pneumococcus. Three of the newly isolated bacteriophages differ serologically from pneumococcus bacteriophages described previously. The ability to yield lytic phage was lost by two of the lysogenic pneumococcal strains on repeated subculture.", "contents": "Lysogeny in pneumococci freshly isolated from man. Twelve strains of encapsulated pneumococci isolated from patients with pneumococcal disease were examined for the presence of bacteriophage. Four of the strains yielded phage lytic for a noncapsulated indicator strain of pneumococcus. Three of the newly isolated bacteriophages differ serologically from pneumococcus bacteriophages described previously. The ability to yield lytic phage was lost by two of the lysogenic pneumococcal strains on repeated subculture."}
{"id": "PMID:12566", "title": "Control of gamete formation (exflagellation) in malaria parasites.", "content": "The only stages of malaria parasites capable of establishing an infection in a mosquito are the gametocytes that circulate in the blood of the veterbrate host. Within minutes of ingestion by a mosquito the gametocytes transform into mature gametes in the process of \"exflagellation.\" This process is controlled in vitro solely by the change in pH in the blood as it moves from the environment of the circulation to that of the atmosphere, the pH rise being mediated by the fall in carbon dioxide tension as the blood equilibrates with the atmosphere.", "contents": "Control of gamete formation (exflagellation) in malaria parasites. The only stages of malaria parasites capable of establishing an infection in a mosquito are the gametocytes that circulate in the blood of the veterbrate host. Within minutes of ingestion by a mosquito the gametocytes transform into mature gametes in the process of \"exflagellation.\" This process is controlled in vitro solely by the change in pH in the blood as it moves from the environment of the circulation to that of the atmosphere, the pH rise being mediated by the fall in carbon dioxide tension as the blood equilibrates with the atmosphere."}
{"id": "PMID:12577", "title": "Beta-adrenoceptor blocking drugs and their use in hypertension.", "content": "Beta-adrenoceptor blocking drugs have been found to be effective antihypertensive agents of similar efficacy to sympathetic inhibitory drugs and methyldopa. They have the advantage of not causing postural or exercise hypotension. While the antihypertensive effect is a function of beta-receptor blockade, the precise mode of action is unknown.", "contents": "Beta-adrenoceptor blocking drugs and their use in hypertension. Beta-adrenoceptor blocking drugs have been found to be effective antihypertensive agents of similar efficacy to sympathetic inhibitory drugs and methyldopa. They have the advantage of not causing postural or exercise hypotension. While the antihypertensive effect is a function of beta-receptor blockade, the precise mode of action is unknown."}
{"id": "PMID:12578", "title": "Acid-base determinations in normal and asphyxiated term infants during the first 24 hours of life.", "content": "Vigorous term infants who are born normally initially have a moderate metabolic and respiratory acidosis which is corrected by the time the infant is 6 hours old. Asphyxiated infants consistently show a greater degree of acidosis, both metabolic and respiratory. Caesarean section results in higher pCO2 values, especially when 'diffusion apnoea' occurs. Indications for the correction of acidosis in asphyxia are proposed.", "contents": "Acid-base determinations in normal and asphyxiated term infants during the first 24 hours of life. Vigorous term infants who are born normally initially have a moderate metabolic and respiratory acidosis which is corrected by the time the infant is 6 hours old. Asphyxiated infants consistently show a greater degree of acidosis, both metabolic and respiratory. Caesarean section results in higher pCO2 values, especially when 'diffusion apnoea' occurs. Indications for the correction of acidosis in asphyxia are proposed."}
{"id": "PMID:12579", "title": "A metabolic approach to the evaluation of peripheral vascular disease.", "content": "Thirty-five patients with occlusive disease of the arteries underwent metabolic studies. The arteriovenous differences of lactate, glucose and oxygen varied with the severity of the ischemic process, as assessed clinically. Lactate release and glucose extraction were significantly different from control values of patients with rest pain or with ischemic gangrene, while values in patients with claudication were comparable with those in the control group. Percutaneous muscle surface pH measurements, which reflect lactate release, decreased directly with diminished perfusion. Metabolic assessment of arterial occlusive disease may prove to be a useful clinical approach.", "contents": "A metabolic approach to the evaluation of peripheral vascular disease. Thirty-five patients with occlusive disease of the arteries underwent metabolic studies. The arteriovenous differences of lactate, glucose and oxygen varied with the severity of the ischemic process, as assessed clinically. Lactate release and glucose extraction were significantly different from control values of patients with rest pain or with ischemic gangrene, while values in patients with claudication were comparable with those in the control group. Percutaneous muscle surface pH measurements, which reflect lactate release, decreased directly with diminished perfusion. Metabolic assessment of arterial occlusive disease may prove to be a useful clinical approach."}
{"id": "PMID:12580", "title": "Leukocyte phagocytic function and dysfunction.", "content": "Although some species of bacteria are killed in vitro by humoral factors in cell-free serum, the in vivo experience with leukopenic patients illustrates the critical role played by phagocytic leukocytes in host resistance to infection. Effective ingestion and killing of micro-organisms requires the sequential and integrated function of the elements of the phagocytic system. Each step in the phagocytic process is also a potential crack in the armor of host defense, and an increasing number of clinically significant disorders of phagocytic function are being recognized and described (5). The phagocytic leukocytes are equipped with a variety of intracellular microbicidal mechanisms which provide a degree of overkill capacity and allow these cells to meet the challenges posed by the many and varied microbial transfressors. Undoubtedly, other phagocytic disorders will be discovered and other important aspects of the intraleukocyte killing mechanisms will be elucidated. For instance, little is known about the function of leukocytes within the relatively hypoxic environment of injured tissue where so many bacterial infections begin. As our understanding of phagocytic function develops, new ways may be found to augment host resistance by preservation or stimulation of the phagocytes.", "contents": "Leukocyte phagocytic function and dysfunction. Although some species of bacteria are killed in vitro by humoral factors in cell-free serum, the in vivo experience with leukopenic patients illustrates the critical role played by phagocytic leukocytes in host resistance to infection. Effective ingestion and killing of micro-organisms requires the sequential and integrated function of the elements of the phagocytic system. Each step in the phagocytic process is also a potential crack in the armor of host defense, and an increasing number of clinically significant disorders of phagocytic function are being recognized and described (5). The phagocytic leukocytes are equipped with a variety of intracellular microbicidal mechanisms which provide a degree of overkill capacity and allow these cells to meet the challenges posed by the many and varied microbial transfressors. Undoubtedly, other phagocytic disorders will be discovered and other important aspects of the intraleukocyte killing mechanisms will be elucidated. For instance, little is known about the function of leukocytes within the relatively hypoxic environment of injured tissue where so many bacterial infections begin. As our understanding of phagocytic function develops, new ways may be found to augment host resistance by preservation or stimulation of the phagocytes."}
{"id": "PMID:12591", "title": "Scanning electron microscopic and electrophoretic studies on clotting factor adsorbents.", "content": "Physical studies carried out on a range of protein and clotting factor adsorbents revealed marked morphological and charge differences. Their appearance in the scanning electron microscope could be used to classify the insoluble precipitates, calcijm phosphate, barium sulphate and citrate, as either amorphorous or crystalline. Surface charge is difficult to define but the present studies on the sparingly-soluble salts, based on calcium and barium, have revealed that they can be subdivided on the basis of the presence or absence of a charge reversal point in the pH-mobility curve. The anion component appeared to determine this characteristic; it was noted that phosphate and citrate ions had a marked effect and gave a biased negative potential at all pH values. We concluded that where a divalent cation is cohabiting with a trivalent anion, the greater potential-determining ability of the latter will dominate the overall charge at the surface of a particle, even below pH7 and the absence of a positive potential gives a monophasic pH-mobility curve. Differences in both the physical appearance and electrophoretic mobility of the adsorbents studied reflect the wide variation in their chemical composition, especially among the various forms of calcium phosphate which, unlike barium sulphate, can include substituted ions such as hydroxyl, in their crystal lattice. The definition of these characteristics allows their behaviour towards clotting factors to be more easily predicted.", "contents": "Scanning electron microscopic and electrophoretic studies on clotting factor adsorbents. Physical studies carried out on a range of protein and clotting factor adsorbents revealed marked morphological and charge differences. Their appearance in the scanning electron microscope could be used to classify the insoluble precipitates, calcijm phosphate, barium sulphate and citrate, as either amorphorous or crystalline. Surface charge is difficult to define but the present studies on the sparingly-soluble salts, based on calcium and barium, have revealed that they can be subdivided on the basis of the presence or absence of a charge reversal point in the pH-mobility curve. The anion component appeared to determine this characteristic; it was noted that phosphate and citrate ions had a marked effect and gave a biased negative potential at all pH values. We concluded that where a divalent cation is cohabiting with a trivalent anion, the greater potential-determining ability of the latter will dominate the overall charge at the surface of a particle, even below pH7 and the absence of a positive potential gives a monophasic pH-mobility curve. Differences in both the physical appearance and electrophoretic mobility of the adsorbents studied reflect the wide variation in their chemical composition, especially among the various forms of calcium phosphate which, unlike barium sulphate, can include substituted ions such as hydroxyl, in their crystal lattice. The definition of these characteristics allows their behaviour towards clotting factors to be more easily predicted."}
{"id": "PMID:12592", "title": "Competitive inhibition by lithium and hydrogen ions of the effect of calcium on the aggregation of rabbit platelets.", "content": "ADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8.", "contents": "Competitive inhibition by lithium and hydrogen ions of the effect of calcium on the aggregation of rabbit platelets. ADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8."}
{"id": "PMID:12593", "title": "Effects of bupranolol, a new beta-blocker, on platelet functions of rabbit and human in vitro.", "content": "The effects of bupranolol, a new beta-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known beta-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased. Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4-3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the beta-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8-3.3 times as effectively as propranolol. From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.", "contents": "Effects of bupranolol, a new beta-blocker, on platelet functions of rabbit and human in vitro. The effects of bupranolol, a new beta-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known beta-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased. Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4-3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the beta-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8-3.3 times as effectively as propranolol. From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis."}
{"id": "PMID:12594", "title": "Effects of ions on ADP-induced aggregation of bovine or human platelets.", "content": "Effects of divalent cations on ADP-induced aggregation response were examined. Bovine platelets were transferred by Sepharose 2B gel filtration from citrate-PRP into citrate free buffer (buffer-GFP). Response increases, reaches a maximum and decreases with increasing calcium and/or magnesium concentration. For either calcium or magnesium alone, increasing response is proportional to a rate coefficient and, through an apparent ion-platelet association constant, to the fraction of platelet critical sites bound to cation. With both ions present, bound magnesium appears to inhibit bound calcium in excess of that accounted for by competition and a lower rate coefficient for bound magnesium. With citrate present in buffer-GFP, apparent association constants increase, excess magnesium inhibition is present, but systems are path dependent. Initial conditions appear to establish a response which is thereafter immutable to environmental magnesium alteration. Citrate-PRP resembles buffer-GFP: response is sensitive to the selective removal of calcium and excess magnesium inhibition is present. With heparin-PRP, response is immutable to the selective removal of approximately 90% of initial calcium. The dependency of response inhibition observed at high divalent cation concentrations indicates that aggregation is not due to interplatelet cross linking by ions. Ion effects are similar for bovine and human platelets.", "contents": "Effects of ions on ADP-induced aggregation of bovine or human platelets. Effects of divalent cations on ADP-induced aggregation response were examined. Bovine platelets were transferred by Sepharose 2B gel filtration from citrate-PRP into citrate free buffer (buffer-GFP). Response increases, reaches a maximum and decreases with increasing calcium and/or magnesium concentration. For either calcium or magnesium alone, increasing response is proportional to a rate coefficient and, through an apparent ion-platelet association constant, to the fraction of platelet critical sites bound to cation. With both ions present, bound magnesium appears to inhibit bound calcium in excess of that accounted for by competition and a lower rate coefficient for bound magnesium. With citrate present in buffer-GFP, apparent association constants increase, excess magnesium inhibition is present, but systems are path dependent. Initial conditions appear to establish a response which is thereafter immutable to environmental magnesium alteration. Citrate-PRP resembles buffer-GFP: response is sensitive to the selective removal of calcium and excess magnesium inhibition is present. With heparin-PRP, response is immutable to the selective removal of approximately 90% of initial calcium. The dependency of response inhibition observed at high divalent cation concentrations indicates that aggregation is not due to interplatelet cross linking by ions. Ion effects are similar for bovine and human platelets."}
{"id": "PMID:12598", "title": "Chemical studies of marine invertebrates. XXIII. A novel polyhydroxylated sterol from the soft coral Litophyton viridis (Coelenterata, Octocorallia, Alcyonacea).", "content": "The structure of 24-methylenecholest-5-en-3beta,7beta,19-triol (II) isolated from the soft coral Litophyton viridis, has been established by X-ray diffraction analysis. The compound is accompanied by its 7-monoacetate derivative.", "contents": "Chemical studies of marine invertebrates. XXIII. A novel polyhydroxylated sterol from the soft coral Litophyton viridis (Coelenterata, Octocorallia, Alcyonacea). The structure of 24-methylenecholest-5-en-3beta,7beta,19-triol (II) isolated from the soft coral Litophyton viridis, has been established by X-ray diffraction analysis. The compound is accompanied by its 7-monoacetate derivative."}
{"id": "PMID:12600", "title": "Induction of increased graft-versus-host disease by mouse spleen cells sensitized in vitro to allogeneic tumor.", "content": "The aim of our study was to sensitize cells in vitro, follow their proliferative and cytotoxic responses, and determine their ability to cause lethal graft-versus-host disease (GVHD). C57BL/6 (H2b) spleen cells were incubated with irradiated BALB/C (H2d) Moloney lymphoma cells (LSTRA) in mixed leukocyte culture conditions for 2, 4, or 6 days and then tested. The maximal proliferative response occurred after 4 days. In vitro cytotoxic reactivity against 51Cr-labeled LSTRA was generated by 4 days (76.3+/-3.1% 51Cr released) and 6 days (133.0+/-4.8%) of sensitization but not by 2 days (-0.2+/-1.1%). Induction of fatal GVHD was assayed by injecting graded doses of the C57BL/6 spleen cells i.v. into adult BALB/c mice pretreated with cyclophosphamide, 180 mg/kg. Cells sensitized for 2 days were effective but no more so than were (control) cells cultured with irradiated C57BL/6 spleen cells. However, cells sensitized longer were far more active than the control cells. Cells sensitized for 4 days killed 70 of 88 mice (80%), and those sensitized for 6 days killed 37 of 48 mice (77%), whereas control cells killed only 42 of 90 mice (47%) (P less than 0.005). Thus, cells sensitized in vitro exhibited an increased ability to induce GVHD in vivo, which was temporally associated with the development of cytotoxicity in vitro.", "contents": "Induction of increased graft-versus-host disease by mouse spleen cells sensitized in vitro to allogeneic tumor. The aim of our study was to sensitize cells in vitro, follow their proliferative and cytotoxic responses, and determine their ability to cause lethal graft-versus-host disease (GVHD). C57BL/6 (H2b) spleen cells were incubated with irradiated BALB/C (H2d) Moloney lymphoma cells (LSTRA) in mixed leukocyte culture conditions for 2, 4, or 6 days and then tested. The maximal proliferative response occurred after 4 days. In vitro cytotoxic reactivity against 51Cr-labeled LSTRA was generated by 4 days (76.3+/-3.1% 51Cr released) and 6 days (133.0+/-4.8%) of sensitization but not by 2 days (-0.2+/-1.1%). Induction of fatal GVHD was assayed by injecting graded doses of the C57BL/6 spleen cells i.v. into adult BALB/c mice pretreated with cyclophosphamide, 180 mg/kg. Cells sensitized for 2 days were effective but no more so than were (control) cells cultured with irradiated C57BL/6 spleen cells. However, cells sensitized longer were far more active than the control cells. Cells sensitized for 4 days killed 70 of 88 mice (80%), and those sensitized for 6 days killed 37 of 48 mice (77%), whereas control cells killed only 42 of 90 mice (47%) (P less than 0.005). Thus, cells sensitized in vitro exhibited an increased ability to induce GVHD in vivo, which was temporally associated with the development of cytotoxicity in vitro."}
{"id": "PMID:12601", "title": "The hydro-chemical and physical conditions of the environment of the immature stages of some species of the simulium (Edwardsellum) damnosum complex (Diptera).", "content": "Water samples were collected from breeding sites of species of the Simulium (Edwardsellum) damnoslm complex in Upper Volta, Liberia and Cameroon during the dry season; and in Tanzania and Kenya at various seasons during a period of two years. The following 20 factors were analysed at 45 breeding sites: water temperature, current velocity, pH value, conductivity free carbon dioxide, oxygen content, calcium, magnesium, potassium, sodium, alkalinity, chloride, sulphate, nitrite, nitrate, ammonium, phosphate, silicate, total iron and organic substance (consumption of potassium permanganate). A number of notable differences in the chemical composition of the water of the breeding sites of 13 S. damnosum complex species were found, particularly with regard to the pH and conductivity. On the basis of these differences the various species can be divided into three main groups: Group I: 3 species (S. sanctipauli, S. yahense, \"Menge\"); breeding in sites with pH values always below 7 and conductivity values below 50 mumhos. Group II: 8 species (S. sirbanum, S. sudanense, S. damnosum s.s., S. squamosum, \"Sanje\", \"Nkusi\", \"Nyamagasani\", \"Jovi\"); breeding in watercourses with neutral, weakly acid or weakly alkaline reactions and conductivity values ranging from 50 to 150 mumhos. Group III: 2 species (\"Kibwezi\", \"Kisiwani\"); breeding in watercourses characterized by highly alkaline reactions with pH values between 7.7 and 10 and by conductivity values between 400 and 950 mumhos. The vectors of Onchocerca volvulus are included in group I and II only.", "contents": "The hydro-chemical and physical conditions of the environment of the immature stages of some species of the simulium (Edwardsellum) damnosum complex (Diptera). Water samples were collected from breeding sites of species of the Simulium (Edwardsellum) damnoslm complex in Upper Volta, Liberia and Cameroon during the dry season; and in Tanzania and Kenya at various seasons during a period of two years. The following 20 factors were analysed at 45 breeding sites: water temperature, current velocity, pH value, conductivity free carbon dioxide, oxygen content, calcium, magnesium, potassium, sodium, alkalinity, chloride, sulphate, nitrite, nitrate, ammonium, phosphate, silicate, total iron and organic substance (consumption of potassium permanganate). A number of notable differences in the chemical composition of the water of the breeding sites of 13 S. damnosum complex species were found, particularly with regard to the pH and conductivity. On the basis of these differences the various species can be divided into three main groups: Group I: 3 species (S. sanctipauli, S. yahense, \"Menge\"); breeding in sites with pH values always below 7 and conductivity values below 50 mumhos. Group II: 8 species (S. sirbanum, S. sudanense, S. damnosum s.s., S. squamosum, \"Sanje\", \"Nkusi\", \"Nyamagasani\", \"Jovi\"); breeding in watercourses with neutral, weakly acid or weakly alkaline reactions and conductivity values ranging from 50 to 150 mumhos. Group III: 2 species (\"Kibwezi\", \"Kisiwani\"); breeding in watercourses characterized by highly alkaline reactions with pH values between 7.7 and 10 and by conductivity values between 400 and 950 mumhos. The vectors of Onchocerca volvulus are included in group I and II only."}
{"id": "PMID:12605", "title": "[Effect of a urea diet on glutamate dehydrogenase and glutamine synthetase activity in various organs of chickens].", "content": "The total values were determined for the activity of glutamate dehydrogenase, glutamine synthetase, and dehydrogenase with pyruvate in broilers fed a diet with a 0, 2 and 4% content of urea for three weeks. A statistically significant increase of glutamate dehydrogenase activity was ascertained in the liver and kidney of broilers. The increase of the activity of glutamine synthetase in liver was close to the threshold of statistical significance. Dehydrogenase activity with pyruvate increased in liver.", "contents": "[Effect of a urea diet on glutamate dehydrogenase and glutamine synthetase activity in various organs of chickens]. The total values were determined for the activity of glutamate dehydrogenase, glutamine synthetase, and dehydrogenase with pyruvate in broilers fed a diet with a 0, 2 and 4% content of urea for three weeks. A statistically significant increase of glutamate dehydrogenase activity was ascertained in the liver and kidney of broilers. The increase of the activity of glutamine synthetase in liver was close to the threshold of statistical significance. Dehydrogenase activity with pyruvate increased in liver."}
{"id": "PMID:12606", "title": "3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. I. Liquid scintillation studies.", "content": "Graft-versus-host-disease was produced in newborn Brown Norway (BN) rats with an intravenous (iv) injection of adult allogeneic Lewis (L) lymph node cells (experimental) and the response was compared to littermates injected with adult syngeneic BN cells (control). By 4 days the reaction in the spleen of experimental animals was such that the spleen index was 1.70 and 2.58 on day 7, and continued to increase until death. A one hour iv pulse of tritiated deoxythymidine (3HdT) administered to experimental and control animals revealed a whole organ peak incorporation of 3HdT on day 6 in experimental spleens. A second larger peak occurred on day 10 in the experimental spleen as compared to a single peak at days 6 or 7, respectively, in the experimental mesenteric and combined superficial lymph nodes. However, analysis of the incorporation of 3HdT with respect to organ weight revealed a peak incorporation in animals receiving L cells on day 4--6 with a second smaller peak on day 10 in the experimental spleen and again a single peak on day 5 or 6 in the lymph nodes. Total 3HdT incorporation within both experimental lymph node compartments became less than controls by day 15 even though experimental nodes had a larger mass. 3HdT incorporation per milligram tissue weight decreased in all tissue compartments of experimental animals by day 13--14. The contribution of donor and host cell proliferation to the various peaks observed is discussed.", "contents": "3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. I. Liquid scintillation studies. Graft-versus-host-disease was produced in newborn Brown Norway (BN) rats with an intravenous (iv) injection of adult allogeneic Lewis (L) lymph node cells (experimental) and the response was compared to littermates injected with adult syngeneic BN cells (control). By 4 days the reaction in the spleen of experimental animals was such that the spleen index was 1.70 and 2.58 on day 7, and continued to increase until death. A one hour iv pulse of tritiated deoxythymidine (3HdT) administered to experimental and control animals revealed a whole organ peak incorporation of 3HdT on day 6 in experimental spleens. A second larger peak occurred on day 10 in the experimental spleen as compared to a single peak at days 6 or 7, respectively, in the experimental mesenteric and combined superficial lymph nodes. However, analysis of the incorporation of 3HdT with respect to organ weight revealed a peak incorporation in animals receiving L cells on day 4--6 with a second smaller peak on day 10 in the experimental spleen and again a single peak on day 5 or 6 in the lymph nodes. Total 3HdT incorporation within both experimental lymph node compartments became less than controls by day 15 even though experimental nodes had a larger mass. 3HdT incorporation per milligram tissue weight decreased in all tissue compartments of experimental animals by day 13--14. The contribution of donor and host cell proliferation to the various peaks observed is discussed."}
{"id": "PMID:12607", "title": "3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. II. Autoradiographic studies.", "content": "A sequential analysis was made of various areas within the lymph nodes and spleen of newborn Brown Norway (BN) rats suffering from graft-versus-host disease (GVHD) subsequent to an allogeneic injection of adult Lewis (L) lymph node cells (experimental). One micron thick autoradiographs were compared between such experimental and control littermates having received the same number of syngeneic adult BN cells. Both experimental and control animals received tritiated deoxythymidine (3HdT) one hour before killing. The autoradiographs revealed a 2.25 and 2.50 times higher thymidine labeling index of lymphocytes in the deep cortex of mesenteric lymph nodes and white pulp of the spleen, respectively, for experimental animals. The experimental effect occurred within one day. The majority of the labeled cells in experimental animals were large lymphoblasts with prominent nucleoli. The labeling index within these areas remained significantly higher than control values until day 8 in the spleen and through day 14 within the lymph nodes. However, differences in labeled cells present in high powered microscopic fields reached a peak on day 3 within compartments in experimental animals but fell significantly below control values by day 9 owing to a pronounced disappearance of both small and large lymphocytes from these areas, and a decreased intensity of individual cell labeling as the reaction progressed. In contradistinction the concentration of labeled cells present in high powered microscopic fields of lymph nodes' medulla became 3.13 times controls by day 4. Most of these labeled cells contained a more basophilic cytoplasm than those found in the deep cortex and some were distinctly plasma cell precursors. In contrast to the deep cortex their concentration remained approximately three times control values until death. The data indicates that the major proliferative events within the spleen and lymph nodes in neonatal rat GVHD are initially restricted to donor cell localization areas of these tissue compartments. Subsequently the GVHD-related events may be attributed to other areas and possibly cell types. Thus any proliferation contributing to splenomegaly in the latter stages of GVHD appears to occur in the red pulp and that contributing to lymph node enlargement a medullary response.", "contents": "3H-deoxythymidine incorporation in graft-versus-host disease in the Norway rat. II. Autoradiographic studies. A sequential analysis was made of various areas within the lymph nodes and spleen of newborn Brown Norway (BN) rats suffering from graft-versus-host disease (GVHD) subsequent to an allogeneic injection of adult Lewis (L) lymph node cells (experimental). One micron thick autoradiographs were compared between such experimental and control littermates having received the same number of syngeneic adult BN cells. Both experimental and control animals received tritiated deoxythymidine (3HdT) one hour before killing. The autoradiographs revealed a 2.25 and 2.50 times higher thymidine labeling index of lymphocytes in the deep cortex of mesenteric lymph nodes and white pulp of the spleen, respectively, for experimental animals. The experimental effect occurred within one day. The majority of the labeled cells in experimental animals were large lymphoblasts with prominent nucleoli. The labeling index within these areas remained significantly higher than control values until day 8 in the spleen and through day 14 within the lymph nodes. However, differences in labeled cells present in high powered microscopic fields reached a peak on day 3 within compartments in experimental animals but fell significantly below control values by day 9 owing to a pronounced disappearance of both small and large lymphocytes from these areas, and a decreased intensity of individual cell labeling as the reaction progressed. In contradistinction the concentration of labeled cells present in high powered microscopic fields of lymph nodes' medulla became 3.13 times controls by day 4. Most of these labeled cells contained a more basophilic cytoplasm than those found in the deep cortex and some were distinctly plasma cell precursors. In contrast to the deep cortex their concentration remained approximately three times control values until death. The data indicates that the major proliferative events within the spleen and lymph nodes in neonatal rat GVHD are initially restricted to donor cell localization areas of these tissue compartments. Subsequently the GVHD-related events may be attributed to other areas and possibly cell types. Thus any proliferation contributing to splenomegaly in the latter stages of GVHD appears to occur in the red pulp and that contributing to lymph node enlargement a medullary response."}
{"id": "PMID:12615", "title": "[Interaction of complex esters of hydroxyethylsulfones with DNA in vitro].", "content": "The effect of a number of alkyl disulphones on the parameters of DNA melting following its treatment with the substances involved was studied under in vitro conditions: it was found that bis(acetyl oxyethylsulphonyl) methane and bis (formyl oxyethylsulphonyl) methane reduced the temperature of DNA melting. As a result of decomposition of oxyethylsulphone esters the corresponding vinylsulphones were formed. It is suggested that the parameters of DNA melting change under the influence of vinylsulphones being formed. There is some correlation between antitumor activity of alkyl disulphones and their capacity to interact with DNA. Inactive or insignificantly active substances would not influence the parameters of DNA melting, while the two substances under consideration possessed a high antitumor effect on ascites forms of animal tumors.", "contents": "[Interaction of complex esters of hydroxyethylsulfones with DNA in vitro]. The effect of a number of alkyl disulphones on the parameters of DNA melting following its treatment with the substances involved was studied under in vitro conditions: it was found that bis(acetyl oxyethylsulphonyl) methane and bis (formyl oxyethylsulphonyl) methane reduced the temperature of DNA melting. As a result of decomposition of oxyethylsulphone esters the corresponding vinylsulphones were formed. It is suggested that the parameters of DNA melting change under the influence of vinylsulphones being formed. There is some correlation between antitumor activity of alkyl disulphones and their capacity to interact with DNA. Inactive or insignificantly active substances would not influence the parameters of DNA melting, while the two substances under consideration possessed a high antitumor effect on ascites forms of animal tumors."}
{"id": "PMID:12616", "title": "Contributions to the optimal use of human blood. VIII. Stability of blood coagulation factor VII during collection and storage of whole blood and plasma.", "content": "Investigations were performed concerning the influence of the pH on the stability of factor VIII during the collection of blood and during the storage of blood and plasma for varying periods and at varying temperatures. It was found that the low pH of ACD anticoagulant solution (pH 4.9) caused a loss of factor VIII procoagulant activity of 10-15% during the collection of blood. However, when less acidic anticoagulant solutions were used, substantial losses of factor VIII occurred during the storage of blood. We concluded that the optimal pH of both the anticoagulant solution and the stored blood, should be between 6.7 and 7.0. However, no anticoagulant solution is known that meets these requirements. In practice ACD ensures the highest recovery of factor VIII in cryoprecipitate, at least in those cases where the blood donations are stored for several hours before separation and freezing of the plasma.", "contents": "Contributions to the optimal use of human blood. VIII. Stability of blood coagulation factor VII during collection and storage of whole blood and plasma. Investigations were performed concerning the influence of the pH on the stability of factor VIII during the collection of blood and during the storage of blood and plasma for varying periods and at varying temperatures. It was found that the low pH of ACD anticoagulant solution (pH 4.9) caused a loss of factor VIII procoagulant activity of 10-15% during the collection of blood. However, when less acidic anticoagulant solutions were used, substantial losses of factor VIII occurred during the storage of blood. We concluded that the optimal pH of both the anticoagulant solution and the stored blood, should be between 6.7 and 7.0. However, no anticoagulant solution is known that meets these requirements. In practice ACD ensures the highest recovery of factor VIII in cryoprecipitate, at least in those cases where the blood donations are stored for several hours before separation and freezing of the plasma."}
{"id": "PMID:12617", "title": "In vivo and in vitro activation of T-antigen receptors on leukocytes and platelets.", "content": "Serological studies on a patient whose red cells are polyagglutinable due to T activation have demonstrated concomitant T activity of the separated leukocytes and platelets. Normal leukocytes and platelets are not T active, but activation can be induced in vitro by treatment with neuraminidase or with pneumococcus type III filtrate. Such T-active cells absorb anti-T from Arachis hypogea lectin. Tests on idfferent types of separated leukocytes show that both neutrophils and lymphocytes have latent T antigen receptors. Neuraminidase treatment of platelets does not change their ability to promote clot retraction, to aggregate with ADP, or to take up serotonin.", "contents": "In vivo and in vitro activation of T-antigen receptors on leukocytes and platelets. Serological studies on a patient whose red cells are polyagglutinable due to T activation have demonstrated concomitant T activity of the separated leukocytes and platelets. Normal leukocytes and platelets are not T active, but activation can be induced in vitro by treatment with neuraminidase or with pneumococcus type III filtrate. Such T-active cells absorb anti-T from Arachis hypogea lectin. Tests on idfferent types of separated leukocytes show that both neutrophils and lymphocytes have latent T antigen receptors. Neuraminidase treatment of platelets does not change their ability to promote clot retraction, to aggregate with ADP, or to take up serotonin."}
{"id": "PMID:12619", "title": "Neurochemistry and behavior in man.", "content": "The distribution and functions of certain neurotransmitter substances seem to correlate with clinical, anatomical and physiological evidence about the mediation of normal and abnormal behaviors in man, though much remains to be learned. The biosynthetic and metabolic pathways, receptors and reuptake mechanisms, and relationships to cyclic nucleotides for several major neurotransmitters are characterized, as well as the specific actions of many behavior-modifying drugs employed clinically. Experimental systems, including nerve cells in culture, permit tests of molecular actions inferred from biochemical and neurophysiological analyses in intact brain. This selective review emphasizes advances in neurochemistry which provide a context for current and future research on neurological and psychiatric disorders encountered in clinical practice.", "contents": "Neurochemistry and behavior in man. The distribution and functions of certain neurotransmitter substances seem to correlate with clinical, anatomical and physiological evidence about the mediation of normal and abnormal behaviors in man, though much remains to be learned. The biosynthetic and metabolic pathways, receptors and reuptake mechanisms, and relationships to cyclic nucleotides for several major neurotransmitters are characterized, as well as the specific actions of many behavior-modifying drugs employed clinically. Experimental systems, including nerve cells in culture, permit tests of molecular actions inferred from biochemical and neurophysiological analyses in intact brain. This selective review emphasizes advances in neurochemistry which provide a context for current and future research on neurological and psychiatric disorders encountered in clinical practice."}
{"id": "PMID:12621", "title": "[Fermentation of pyruvate by 7 species of phototrophic purple bacteria].", "content": "The dark, anaerobic fermentation of pyruvate under growth conditions was examined with the following species of phototrophic purple bacteria: Rhodospirillum rubrum strains Ha and S1, Rhodopseudomonas gelatinosa strain 2150, Rhodopseudomonas acidophila strain 7050, Rhodopseudomonas palustris strain ATCC 17001, Rhodopseudomonas capsulata strains Kb1 and 6950, Rhodopseudomonas sphaeroides strain ATCC 17023, and Chromatium vinosum strain D. Fermentation balances were established for all experiments. Under fermentative conditions cell protein and dry weight increased only slightly, if at all. The species differed considerably in their fermentative activity; R. rubrum and R. gelatinosa exhibited the highest rates (2-8 mumoles pyruvate/mg protein-h). R. acidophila and R. capsulata showed an intermediate fermentation rate (0.4--2.0 mumoles pyruvate/mg protein-h), while the other strains tested fermented at quite low rates (0.2-0.4 mumoles pyruvate/mg protein-h). The extremes of fermentation times were from 30-380 hours. Based on the products of fermentation which were formed in addition to acetate, formate, and CO2, the species can be grouped as follows: a) R. rubrum, R. gelatinosa, and R. sphaeroides additionally form propionate. b) R. gelatinosa, R. palustris, R. capsulata, R. sphaeroides, and C. vinosum additionally form lactate. R. palustris also produces butyrate. c) R. acidophila and R. capsulata additionally form much 2,3-butanediol, acetoin, and diacetyl. Small amounts of acetoin were formed by the rest of the strains. A comparison of the fermentation of pyruvate by normal and starved cells (4 days in the light without a carbon source) of R. rubrum and R. gelatinosa shows that the latter ferment more slowly and produce less acetate and formate, but more propionate or lactate. The fermentation of pyruvate by R. rubrum was also studied in cultures in which the pH fell (7.2--6.6). Compared with the fermentation at neutral pH (7.3, 7.4), the following differences were found: a slower fermentation rate, an increased production of dry weight, an increased formation of propionate, but a reduced formation of acetate and a very low production of formate.", "contents": "[Fermentation of pyruvate by 7 species of phototrophic purple bacteria]. The dark, anaerobic fermentation of pyruvate under growth conditions was examined with the following species of phototrophic purple bacteria: Rhodospirillum rubrum strains Ha and S1, Rhodopseudomonas gelatinosa strain 2150, Rhodopseudomonas acidophila strain 7050, Rhodopseudomonas palustris strain ATCC 17001, Rhodopseudomonas capsulata strains Kb1 and 6950, Rhodopseudomonas sphaeroides strain ATCC 17023, and Chromatium vinosum strain D. Fermentation balances were established for all experiments. Under fermentative conditions cell protein and dry weight increased only slightly, if at all. The species differed considerably in their fermentative activity; R. rubrum and R. gelatinosa exhibited the highest rates (2-8 mumoles pyruvate/mg protein-h). R. acidophila and R. capsulata showed an intermediate fermentation rate (0.4--2.0 mumoles pyruvate/mg protein-h), while the other strains tested fermented at quite low rates (0.2-0.4 mumoles pyruvate/mg protein-h). The extremes of fermentation times were from 30-380 hours. Based on the products of fermentation which were formed in addition to acetate, formate, and CO2, the species can be grouped as follows: a) R. rubrum, R. gelatinosa, and R. sphaeroides additionally form propionate. b) R. gelatinosa, R. palustris, R. capsulata, R. sphaeroides, and C. vinosum additionally form lactate. R. palustris also produces butyrate. c) R. acidophila and R. capsulata additionally form much 2,3-butanediol, acetoin, and diacetyl. Small amounts of acetoin were formed by the rest of the strains. A comparison of the fermentation of pyruvate by normal and starved cells (4 days in the light without a carbon source) of R. rubrum and R. gelatinosa shows that the latter ferment more slowly and produce less acetate and formate, but more propionate or lactate. The fermentation of pyruvate by R. rubrum was also studied in cultures in which the pH fell (7.2--6.6). Compared with the fermentation at neutral pH (7.3, 7.4), the following differences were found: a slower fermentation rate, an increased production of dry weight, an increased formation of propionate, but a reduced formation of acetate and a very low production of formate."}
{"id": "PMID:12625", "title": "Purification and some properties of factor D of the human properdin system.", "content": "Factor D has been purified by gel and ion exchange chromatographies, and by ultrafiltration through different membranes. The final preparation appeared pure in various analytical tests. The molecular weight of human D is 21,500 according to gel chromatography, the isoelectric point was found at pH 7.8. Factor D is an active esterolytic enzyme, it cleaves N-alpha-acetyl-L-lysine methyl ester and N-alpha-acetyl-L-glycyl-L-lysine methyl ester. Both peptide esters inhibit the hydrolytic activation of factor B by D in the presence of cobra venom factor. D is also inhibited by diisopropyl-fluorophosphate and by penylmethyl-sulfonyl-flouride.", "contents": "Purification and some properties of factor D of the human properdin system. Factor D has been purified by gel and ion exchange chromatographies, and by ultrafiltration through different membranes. The final preparation appeared pure in various analytical tests. The molecular weight of human D is 21,500 according to gel chromatography, the isoelectric point was found at pH 7.8. Factor D is an active esterolytic enzyme, it cleaves N-alpha-acetyl-L-lysine methyl ester and N-alpha-acetyl-L-glycyl-L-lysine methyl ester. Both peptide esters inhibit the hydrolytic activation of factor B by D in the presence of cobra venom factor. D is also inhibited by diisopropyl-fluorophosphate and by penylmethyl-sulfonyl-flouride."}
{"id": "PMID:12632", "title": "Volatile degradation products of l-dehydroascorbic acid.", "content": "Volatile degradation products were isolated from a solution of L-dehydroascorbic acid in phosphate buffer solution of pH 2,4,6 and 8 heated under reflux for 3 h or left at 25 degrees C for 200 h. The products were identified by comparison of their gas chromatographic retention data, infra-red and mass spectra with those of authentic compounds. Fifteen products were identified,  among which 12 had not yet been reported as degradation products of L-dehydroascorbic acid. Concentrations of 5 main degradation products, i.e. 3-hydroxy-2-pyrone, 2-furancarboxylic acid, 2-furaldehyde, acetic acid and 2-acetylfuran depended on the pH values and temperature; the presence of oxygen had no pronounced effect.", "contents": "Volatile degradation products of l-dehydroascorbic acid. Volatile degradation products were isolated from a solution of L-dehydroascorbic acid in phosphate buffer solution of pH 2,4,6 and 8 heated under reflux for 3 h or left at 25 degrees C for 200 h. The products were identified by comparison of their gas chromatographic retention data, infra-red and mass spectra with those of authentic compounds. Fifteen products were identified,  among which 12 had not yet been reported as degradation products of L-dehydroascorbic acid. Concentrations of 5 main degradation products, i.e. 3-hydroxy-2-pyrone, 2-furancarboxylic acid, 2-furaldehyde, acetic acid and 2-acetylfuran depended on the pH values and temperature; the presence of oxygen had no pronounced effect."}
{"id": "PMID:12634", "title": "Surface tension activity and paramorphogenic effect of sorbose, sodium desoxycholate, and griseofulvin on the growth of colonies of Chaetomium aureum Chivers.", "content": "Sorbose at 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0% levels, sodium-desoxycholate at 0.025, 0.050, 0.075, 0.1 and 0.125% levels, and griseofulvin at 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, and 0.010% levels restrict the growth of colonies of Chaetomium aureum, both at pH 6.5 and 7.0. Restriction of colonies was most effective with 0.7% sorbose, 0.1% sodium-desoxycholate, and 0.006% griseofulvin in the medium adjusted to pH 6.5. Surface tension activity of sorbose, sodium-desoxycholate, and griseofulvin in different concentrations was determined, following the usual standard method.", "contents": "Surface tension activity and paramorphogenic effect of sorbose, sodium desoxycholate, and griseofulvin on the growth of colonies of Chaetomium aureum Chivers. Sorbose at 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0% levels, sodium-desoxycholate at 0.025, 0.050, 0.075, 0.1 and 0.125% levels, and griseofulvin at 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, and 0.010% levels restrict the growth of colonies of Chaetomium aureum, both at pH 6.5 and 7.0. Restriction of colonies was most effective with 0.7% sorbose, 0.1% sodium-desoxycholate, and 0.006% griseofulvin in the medium adjusted to pH 6.5. Surface tension activity of sorbose, sodium-desoxycholate, and griseofulvin in different concentrations was determined, following the usual standard method."}
{"id": "PMID:12635", "title": "[New findings on human prolactin].", "content": "Since prolactin (HPRL) occurs as a separate pituitary hormone in man the paper will discuss results about the mechanisms involved regulation of HPRL secretion. A number of factors which lead to an increase in HPRL secretion are named. The clinical relevance of HPRL inhibiting substances as L-DOPA and 2-Br-alpha-ergocryptine is mentioned. The influence of HPRL in pregnancy and lactation period is described also the regulative effect of HPRL on hormone-dependent breast tumors.", "contents": "[New findings on human prolactin]. Since prolactin (HPRL) occurs as a separate pituitary hormone in man the paper will discuss results about the mechanisms involved regulation of HPRL secretion. A number of factors which lead to an increase in HPRL secretion are named. The clinical relevance of HPRL inhibiting substances as L-DOPA and 2-Br-alpha-ergocryptine is mentioned. The influence of HPRL in pregnancy and lactation period is described also the regulative effect of HPRL on hormone-dependent breast tumors."}
{"id": "PMID:12636", "title": "[Production of obstetrical reports using a computer].", "content": "A rational method of production of medical reports in obstetrics is reported. The basis of this method is the approved computer guided system (DOKUMEDA) in clinics of radiology. Advantages and disadvantages of using are discussed.", "contents": "[Production of obstetrical reports using a computer]. A rational method of production of medical reports in obstetrics is reported. The basis of this method is the approved computer guided system (DOKUMEDA) in clinics of radiology. Advantages and disadvantages of using are discussed."}
{"id": "PMID:12638", "title": "Chitinase and beta-N-acetylglycosaminidase in the digestive juice of Helix pomatia.", "content": "A beta-N-acetylglucosaminidase from Helix pomatia digestive juice was separated and partly purified by gel chromatography. The optimal pH for the degradation of p-nitrophenyl-N-acetyl-beta-D-glucosaminide was 3.4. The molecular weight was around 160 000 and the pI = 4.95. In the same gel chromatography run two chitinase active peaks were also obtained. These chitinase active peaks were also obtained. These chitinases, with molecular weights around 26 000 and 13 000, had somewhat different pH activity curves with optima at 4.2 and 4.3. By isoelectric focusing the first peak with molecular weight around 26 000 was divided in two chitinase active regions with pI at 5.7 and 3.5. The second peak with molecular weight around 13 000 had a pI at 7.3.", "contents": "Chitinase and beta-N-acetylglycosaminidase in the digestive juice of Helix pomatia. A beta-N-acetylglucosaminidase from Helix pomatia digestive juice was separated and partly purified by gel chromatography. The optimal pH for the degradation of p-nitrophenyl-N-acetyl-beta-D-glucosaminide was 3.4. The molecular weight was around 160 000 and the pI = 4.95. In the same gel chromatography run two chitinase active peaks were also obtained. These chitinase active peaks were also obtained. These chitinases, with molecular weights around 26 000 and 13 000, had somewhat different pH activity curves with optima at 4.2 and 4.3. By isoelectric focusing the first peak with molecular weight around 26 000 was divided in two chitinase active regions with pI at 5.7 and 3.5. The second peak with molecular weight around 13 000 had a pI at 7.3."}
{"id": "PMID:12639", "title": "Absorption of free and antibody-conjugated horseradish peroxidase to fixed glial cells in tissue culture, a possible source of error in immunohistochemistry.", "content": "Incubation of cellular preparations with antibody-conjugated peroxidase result in a very strong unspecific staining, for one electropolar binding of the basic enzymic protein with the cell structures. In immunohistochemical practice, it may represent an evil as import as when dealing with immunofluorescence techniques. This background can to a great extent be avoided by rinsing the preparations in buffer at pH = 6.2.", "contents": "Absorption of free and antibody-conjugated horseradish peroxidase to fixed glial cells in tissue culture, a possible source of error in immunohistochemistry. Incubation of cellular preparations with antibody-conjugated peroxidase result in a very strong unspecific staining, for one electropolar binding of the basic enzymic protein with the cell structures. In immunohistochemical practice, it may represent an evil as import as when dealing with immunofluorescence techniques. This background can to a great extent be avoided by rinsing the preparations in buffer at pH = 6.2."}
{"id": "PMID:12647", "title": "Effect of continuous positive airway pressure breathing on cardiorespiratory function in infants with respiratory distress syndrome.", "content": "A method of investigating the cardiorespiratory responses to continuous positive airway presslre (CPAP) in infants with respiratory distress syndrome is described. All measurements were made immediately before and within five minutes of application or any change in level of CPAP. Ventilation was derived from a pneumotachograph and dynamic compliance calculated. We have also measured arterial pH, oxygen and carbon dioxide tensions, arterial blood pressure and central venous pressure. Arterial oxygen tension increased in association with a decrease in the alveolar-arterial oxygen gradient. No consistent changes occurred in pH or carbon dioxide tension. Heart rate and mean arterial blood pressure remained the same but the arterial pulse pressure narrowed and the increase in central venous pressure averaged 17% of the applied airway pressure. There were less variations in both tidal volumes and instantaneous respiratory rates with CPAP compared with spontaneous breathing without CPAP. The respiratory rate decreased, but there were no consistent changes in tidal volume, resulting in a lesser reduction of minute ventilation. Dynamic compliance decreased on CPAP. With correct use of CPAP, and improvement in oxygenation generally occurs without obvious adverse cardiorespiratory effects. CPAP must nevertheless be used cautiously and in conjunction with close monitoring; because when the appropriate pressures are exceeded, it is possible that both circulatory and ventilatory function might be severely compromised.", "contents": "Effect of continuous positive airway pressure breathing on cardiorespiratory function in infants with respiratory distress syndrome. A method of investigating the cardiorespiratory responses to continuous positive airway presslre (CPAP) in infants with respiratory distress syndrome is described. All measurements were made immediately before and within five minutes of application or any change in level of CPAP. Ventilation was derived from a pneumotachograph and dynamic compliance calculated. We have also measured arterial pH, oxygen and carbon dioxide tensions, arterial blood pressure and central venous pressure. Arterial oxygen tension increased in association with a decrease in the alveolar-arterial oxygen gradient. No consistent changes occurred in pH or carbon dioxide tension. Heart rate and mean arterial blood pressure remained the same but the arterial pulse pressure narrowed and the increase in central venous pressure averaged 17% of the applied airway pressure. There were less variations in both tidal volumes and instantaneous respiratory rates with CPAP compared with spontaneous breathing without CPAP. The respiratory rate decreased, but there were no consistent changes in tidal volume, resulting in a lesser reduction of minute ventilation. Dynamic compliance decreased on CPAP. With correct use of CPAP, and improvement in oxygenation generally occurs without obvious adverse cardiorespiratory effects. CPAP must nevertheless be used cautiously and in conjunction with close monitoring; because when the appropriate pressures are exceeded, it is possible that both circulatory and ventilatory function might be severely compromised."}
{"id": "PMID:12648", "title": "The protective action of certain anaesthetics and tranquilizers against the effects of hyperbaric oxygen.", "content": "The protective effects of pentobarbitone, hydroxydione and diazepam against acute and chronic toxicity of high-pressure oxygen (HPO) were studied in rats. During exposure to hyperbaric oxygen body temperature was measured and ECG as well as EMG tracings from the diaphragm were obtained. Long term observations of animals after the exposure to HPO were conducted. Pentobarbitone and hydroxydione reduced the manifestations of acute toxicity but increased those of chronic toxicity. Diazepam reduced the manifestations of acute toxicity and seemed to counteract those of chronic toxicity. Lowering of body temperature of the animals which occurred during exposure to HPO was probably connected with manifestations of chronic toxicity. Observation of the cardiorespiratory functions suggested a possible connection between their disturbances and an onset of seizures and development of oxygen-induced paralysis.", "contents": "The protective action of certain anaesthetics and tranquilizers against the effects of hyperbaric oxygen. The protective effects of pentobarbitone, hydroxydione and diazepam against acute and chronic toxicity of high-pressure oxygen (HPO) were studied in rats. During exposure to hyperbaric oxygen body temperature was measured and ECG as well as EMG tracings from the diaphragm were obtained. Long term observations of animals after the exposure to HPO were conducted. Pentobarbitone and hydroxydione reduced the manifestations of acute toxicity but increased those of chronic toxicity. Diazepam reduced the manifestations of acute toxicity and seemed to counteract those of chronic toxicity. Lowering of body temperature of the animals which occurred during exposure to HPO was probably connected with manifestations of chronic toxicity. Observation of the cardiorespiratory functions suggested a possible connection between their disturbances and an onset of seizures and development of oxygen-induced paralysis."}
{"id": "PMID:12653", "title": "Present state of alpha and beta adrenergic drugs III. Beta blocking agents.", "content": "The beta blocking agents are valuable drugs in cardiology. They are effective in any fast arrhythmia. Together with nitroglycerin, beta blockers are drugs of first choice in angina. As antihypertensives, they have advantages that should make them drugs of first choice. For migraine the beta blockers are equal to any other type of drug. With more study their place in treating anxiety will be clarified. And without question other uses will be found. It is difficult for this author to understand the attitude of the FDA to this class of drugs. To limit the American physician to only one drug in this large group of drugs is unheard of. Although it can be argued that propranolol is the best one, there are obvious cases where another drug would be better. For example, propranolol induces nightmares in a few patients. There is evidence to show that timolol does this less frequently. FDA delay in approval of propranolol for essential hypertension is totally incomprehensible. Other approved drugs are less effective and much more toxic. Propranolol, and the other beta blockers, are safe and effective. The adverse beta effects are easily controlled or avoided. The other adverse effects are no more frequent than with any other class of drugs, and all are reversible. It is to be hoped that science and common sense will prevail over bureaucratic indecision.", "contents": "Present state of alpha and beta adrenergic drugs III. Beta blocking agents. The beta blocking agents are valuable drugs in cardiology. They are effective in any fast arrhythmia. Together with nitroglycerin, beta blockers are drugs of first choice in angina. As antihypertensives, they have advantages that should make them drugs of first choice. For migraine the beta blockers are equal to any other type of drug. With more study their place in treating anxiety will be clarified. And without question other uses will be found. It is difficult for this author to understand the attitude of the FDA to this class of drugs. To limit the American physician to only one drug in this large group of drugs is unheard of. Although it can be argued that propranolol is the best one, there are obvious cases where another drug would be better. For example, propranolol induces nightmares in a few patients. There is evidence to show that timolol does this less frequently. FDA delay in approval of propranolol for essential hypertension is totally incomprehensible. Other approved drugs are less effective and much more toxic. Propranolol, and the other beta blockers, are safe and effective. The adverse beta effects are easily controlled or avoided. The other adverse effects are no more frequent than with any other class of drugs, and all are reversible. It is to be hoped that science and common sense will prevail over bureaucratic indecision."}
{"id": "PMID:12652", "title": "Effects of the H1-antagonist promethazine and the H2-antagonist burimamide on chronotropic, inotropic and coronary vascular responses to histamine in isolated perfused guinea-pig hearts.", "content": "On guinea-pig atria part of the inotropic response to histamine is attributable to a concomitant increase of the frequency [7]. Since the chronotropic effect of histamine is mediated by a stimulation of H2-receptors a direct interaction of histamine with H1-receptors a direct interaction of histamine with H1-receptors mediating the inotropic response on heart may be overlooked. For this reason the ability of the H1-antagonist promethazine and the H2-antagonist burimamide to inhibit the positive chronotropic, inotropic and coronary vascular responses to histamine was determined in spontaneously beating and electrically driven perfused guinea-pig hearts. (1) Burimamide produced a competitive blockade of the positive chrono- and inotropic responses to histamine. (2) On the other hand, promethazine in concentrations that had no effect on cardiac function by itself, proved to be ineffective against the positive chrono- and inotropic responses produced by histamine on spontaneously beating and electrically driven heart preparations. (3) The predominant coronary vasodilation observed after infusion with histamine was competitively antagonized by promethazine and burimamide. This blockade was not attributable to an interaction with myocardial H2-receptors mediating increases in heart rate and contractility and was, therefore, direct in nature. (4) Based upon the present study and former investigations [7] the following distribution of different histamine receptors in the guinea-pig heart does exist: H1-receptors are present in the atrial muscle and the coronary vascular bed. H2-receptors are located in the sinus node, the ventricular myocardium and the coronary vessels.", "contents": "Effects of the H1-antagonist promethazine and the H2-antagonist burimamide on chronotropic, inotropic and coronary vascular responses to histamine in isolated perfused guinea-pig hearts. On guinea-pig atria part of the inotropic response to histamine is attributable to a concomitant increase of the frequency [7]. Since the chronotropic effect of histamine is mediated by a stimulation of H2-receptors a direct interaction of histamine with H1-receptors a direct interaction of histamine with H1-receptors mediating the inotropic response on heart may be overlooked. For this reason the ability of the H1-antagonist promethazine and the H2-antagonist burimamide to inhibit the positive chronotropic, inotropic and coronary vascular responses to histamine was determined in spontaneously beating and electrically driven perfused guinea-pig hearts. (1) Burimamide produced a competitive blockade of the positive chrono- and inotropic responses to histamine. (2) On the other hand, promethazine in concentrations that had no effect on cardiac function by itself, proved to be ineffective against the positive chrono- and inotropic responses produced by histamine on spontaneously beating and electrically driven heart preparations. (3) The predominant coronary vasodilation observed after infusion with histamine was competitively antagonized by promethazine and burimamide. This blockade was not attributable to an interaction with myocardial H2-receptors mediating increases in heart rate and contractility and was, therefore, direct in nature. (4) Based upon the present study and former investigations [7] the following distribution of different histamine receptors in the guinea-pig heart does exist: H1-receptors are present in the atrial muscle and the coronary vascular bed. H2-receptors are located in the sinus node, the ventricular myocardium and the coronary vessels."}
{"id": "PMID:12655", "title": "Takayasu's arteritis. Clinical study of 107 cases.", "content": "The clinical experience derived from the retrospective study of 107 cases of TA over a 19 year period is presented. The disease predominated in females (8.5:1), with age of onset usually less than 20 years. In half of the cases an acute inflammatory phase was observed, characterized mainly by systemic and cardiovascular symptoms. Subsequently the natural course of TA was toward chronicity with gradual  deterioration. The most frequent variety of TA (65 per cent of the patients) was Type III, in which the supra-aortic trunks and the abdominal aorta were involved. The predominant clinical features were reduction of amplitude of peripheral arterial pulses (96 per cent), vascular bruits (94 per cent), and raised blood pressure (72 per cent), mainly resulting from renal arterial involvement (62 per cent). Heart failure (28 per cent) is rarely the result of direct coronary arteritis. TA is most often confused with aortic coarctation, but usually the aortogram distinguishes these. The etiology of TA is discussed. The high incidence of previous and present active tuberculous (48 per cent) in the present series and previous experimental work suggest that tuberculosis may play an important role in the etiology of TA. Treatment for antihypertension and heart failure should be employed when indicated. Treatment with corticosteroids requires further evaluation. Treatment for tuberculosis is not justified in all cases until the exact role of tuberculosis is well established.", "contents": "Takayasu's arteritis. Clinical study of 107 cases. The clinical experience derived from the retrospective study of 107 cases of TA over a 19 year period is presented. The disease predominated in females (8.5:1), with age of onset usually less than 20 years. In half of the cases an acute inflammatory phase was observed, characterized mainly by systemic and cardiovascular symptoms. Subsequently the natural course of TA was toward chronicity with gradual  deterioration. The most frequent variety of TA (65 per cent of the patients) was Type III, in which the supra-aortic trunks and the abdominal aorta were involved. The predominant clinical features were reduction of amplitude of peripheral arterial pulses (96 per cent), vascular bruits (94 per cent), and raised blood pressure (72 per cent), mainly resulting from renal arterial involvement (62 per cent). Heart failure (28 per cent) is rarely the result of direct coronary arteritis. TA is most often confused with aortic coarctation, but usually the aortogram distinguishes these. The etiology of TA is discussed. The high incidence of previous and present active tuberculous (48 per cent) in the present series and previous experimental work suggest that tuberculosis may play an important role in the etiology of TA. Treatment for antihypertension and heart failure should be employed when indicated. Treatment with corticosteroids requires further evaluation. Treatment for tuberculosis is not justified in all cases until the exact role of tuberculosis is well established."}
{"id": "PMID:12656", "title": "Effect of antiserum on transplantable hematopoietic colony-forming units during Rauscher leukemia development.", "content": "Studies have been carried out to determine the sensitivity of hematopoietic CFU-S from Rauscher leukemic mice to an antiserum against the disease prepared in syngeneic mice. Test of this antiserum against Rauscher virus prior to injection showed it to be effective both in vitro and in vivo. At the same time, normal serum was shown to be without effect either against the CFU-S or against the virus. Spleen CFU-S were obtained from control and leukemic mice over a sequence of days following Rauscher virus injection and assayed by transplantation technique. Prior to transplantation these were incubated in vitro in either normal syngeneic serum or syngeneic antiserum. Incubation with antiserum had no effect on CFU-S obtained from the spleens of normal mice. However, incubation in this antiserum of spleen CFU-S from Rauscher leukemic mice resulted in a reduction of up to 50% in their colony-forming ability. Additional tests with guinea pig complement suggested that the levels of inactivation seen are not complement limited. This antiserum-induced reduction in colony formation was first evident in the second week after the injection of virus, coincident with the onset of splenomegaly in the leukemic mice. Thereafter, sensitivity of CFU-S to the antiserlm could be detected up to the terminal point of the leukemia (44 days).", "contents": "Effect of antiserum on transplantable hematopoietic colony-forming units during Rauscher leukemia development. Studies have been carried out to determine the sensitivity of hematopoietic CFU-S from Rauscher leukemic mice to an antiserum against the disease prepared in syngeneic mice. Test of this antiserum against Rauscher virus prior to injection showed it to be effective both in vitro and in vivo. At the same time, normal serum was shown to be without effect either against the CFU-S or against the virus. Spleen CFU-S were obtained from control and leukemic mice over a sequence of days following Rauscher virus injection and assayed by transplantation technique. Prior to transplantation these were incubated in vitro in either normal syngeneic serum or syngeneic antiserum. Incubation with antiserum had no effect on CFU-S obtained from the spleens of normal mice. However, incubation in this antiserum of spleen CFU-S from Rauscher leukemic mice resulted in a reduction of up to 50% in their colony-forming ability. Additional tests with guinea pig complement suggested that the levels of inactivation seen are not complement limited. This antiserum-induced reduction in colony formation was first evident in the second week after the injection of virus, coincident with the onset of splenomegaly in the leukemic mice. Thereafter, sensitivity of CFU-S to the antiserlm could be detected up to the terminal point of the leukemia (44 days)."}
{"id": "PMID:12657", "title": "Multiple endocrine adenomas in a patient with the Maffucci syndrome.", "content": "A patient with multiple cutaneous hemangiomas and skeletal dyschondroplasia (the Maffucci syndrome) was found to have a pituitary chromophobe adenoma, a parathyroid adenoma and two other neoplasms. The presence of two endocrine tumors suggested the syndrome of multiple endocrine adenomatosis, and raised the issue of an etiologic relationship between this disease and the Maffucci syndrome. Dyschondroplasia, however, has no known influence on the secretion of parathyroid hormone or any of the pituitary hormones. The Maffucci syndrome is associated with a high incidence of malignancy, but it involves primarily mesodermal derivatives whereas multiple endocrine adenomatosis affects tissues of ectodermal origin. The association of the two in our patient is probably fortuitous.", "contents": "Multiple endocrine adenomas in a patient with the Maffucci syndrome. A patient with multiple cutaneous hemangiomas and skeletal dyschondroplasia (the Maffucci syndrome) was found to have a pituitary chromophobe adenoma, a parathyroid adenoma and two other neoplasms. The presence of two endocrine tumors suggested the syndrome of multiple endocrine adenomatosis, and raised the issue of an etiologic relationship between this disease and the Maffucci syndrome. Dyschondroplasia, however, has no known influence on the secretion of parathyroid hormone or any of the pituitary hormones. The Maffucci syndrome is associated with a high incidence of malignancy, but it involves primarily mesodermal derivatives whereas multiple endocrine adenomatosis affects tissues of ectodermal origin. The association of the two in our patient is probably fortuitous."}
{"id": "PMID:12660", "title": "A study of the relationship between Goodwin's high-risk score and fetal outcome.", "content": "Correlation between Goodwin's high-risk score and Apgar score was studied in 266 pregnancies managed with the use of the information from clinical monitoring. The correlation coefficients between Goodwin's score and Apgar scores were -0.3178 for one-minute Apgar scores and -0.2668 for five-minute Apgar scores. Both are significant at the level of p less than 0.001. When the patients were divided into two groups by Goodwin's score, fetuses of the group with the higher score (greater than or equal to 4) were significantly more acidotic than those of the group with the lower score. Therefore, Goodwin's high-risk scoring system is simple and useful in the selection of potential risk patients.", "contents": "A study of the relationship between Goodwin's high-risk score and fetal outcome. Correlation between Goodwin's high-risk score and Apgar score was studied in 266 pregnancies managed with the use of the information from clinical monitoring. The correlation coefficients between Goodwin's score and Apgar scores were -0.3178 for one-minute Apgar scores and -0.2668 for five-minute Apgar scores. Both are significant at the level of p less than 0.001. When the patients were divided into two groups by Goodwin's score, fetuses of the group with the higher score (greater than or equal to 4) were significantly more acidotic than those of the group with the lower score. Therefore, Goodwin's high-risk scoring system is simple and useful in the selection of potential risk patients."}
{"id": "PMID:12661", "title": "Pathologic scar formation. Morphologic and biochemical correlates.", "content": "Morphologic and biochemical analyses were performed to compare normal skin and mature scars to hypertrophic scar and keloid. Correlation of morphologic findings with biochemical profiles of the skin and scar samples proved feasible and enlightening. Scanning electron microscopy (SEM) was used to characterize the architectural arrangement of collagen fibers in skin and scars. Cultured fibroblasts from each specimen were also examined with the SEM. A biochemical profile of each tissue specimen was constructed, characterizing the collagen component of the specimen by sequential molecular sieve and ion exchange chromatography to determine a) the degree of intermolecular crosslinking, b) amino acid analysis, and c) levels of lysyl oxidase activity. Results indicate that collagen fibers and fiber bundles display a decreasing level of organization as the clinical degree of scar abnormality increases, and this structural gradient correlates with the gradient of intermolecular crosslinking in the same tissue--normal skin and mature scar being highly crosslinked, hypertrophic and keloid successively less so. Surprisingly, the level of the crosslinking enzyme lysyl oxidase is normal or elevated in hypertrophic scar and keloid despite the relative lack of crosslinking. Amino acid content was uniform for all specimens. Scanning electron microscopy examination of cultured fibroblasts from the tissue specimens demonstrated three phenotypically distinctive fibroblasts whose numerical and volumetric proportions correlated with the tissue of origin.", "contents": "Pathologic scar formation. Morphologic and biochemical correlates. Morphologic and biochemical analyses were performed to compare normal skin and mature scars to hypertrophic scar and keloid. Correlation of morphologic findings with biochemical profiles of the skin and scar samples proved feasible and enlightening. Scanning electron microscopy (SEM) was used to characterize the architectural arrangement of collagen fibers in skin and scars. Cultured fibroblasts from each specimen were also examined with the SEM. A biochemical profile of each tissue specimen was constructed, characterizing the collagen component of the specimen by sequential molecular sieve and ion exchange chromatography to determine a) the degree of intermolecular crosslinking, b) amino acid analysis, and c) levels of lysyl oxidase activity. Results indicate that collagen fibers and fiber bundles display a decreasing level of organization as the clinical degree of scar abnormality increases, and this structural gradient correlates with the gradient of intermolecular crosslinking in the same tissue--normal skin and mature scar being highly crosslinked, hypertrophic and keloid successively less so. Surprisingly, the level of the crosslinking enzyme lysyl oxidase is normal or elevated in hypertrophic scar and keloid despite the relative lack of crosslinking. Amino acid content was uniform for all specimens. Scanning electron microscopy examination of cultured fibroblasts from the tissue specimens demonstrated three phenotypically distinctive fibroblasts whose numerical and volumetric proportions correlated with the tissue of origin."}
{"id": "PMID:12659", "title": "Hyperlactatemia and hemolysis in G6PD deficiency after nitrofurantoin ingestion.", "content": "A 69-year-old man with glucose-6-phosphate dehydrogenase deficiency was treated with nitrofurantoin for pyuria. Four days later he presented with metabolic acidosis due to excess lactic acid, a decline in curculating hemoglobin, reticulocytosis, elevated serum transaminase levels, and hyperbilirubinemia. The drug was withdrawn and the hyperlactatemia subsided in three days without specific treatment. In vitro, nitrofurantoin is capable of stimulating erythrocyte glucose utilization aand lactate production, and inhibiting the generation of reduced glutathione. In vivo, this drug is capable of producing hemolysis in susceptible subjects and hepatocellular injury. The temporal proximity of drug ingestion and hemolysis, increased glucose utilization, lactate excess, and hepatic insufficiency suggests that nitrofurantoin may have been responisble for precipitating the clinical and chemical abnormalities observed.", "contents": "Hyperlactatemia and hemolysis in G6PD deficiency after nitrofurantoin ingestion. A 69-year-old man with glucose-6-phosphate dehydrogenase deficiency was treated with nitrofurantoin for pyuria. Four days later he presented with metabolic acidosis due to excess lactic acid, a decline in curculating hemoglobin, reticulocytosis, elevated serum transaminase levels, and hyperbilirubinemia. The drug was withdrawn and the hyperlactatemia subsided in three days without specific treatment. In vitro, nitrofurantoin is capable of stimulating erythrocyte glucose utilization aand lactate production, and inhibiting the generation of reduced glutathione. In vivo, this drug is capable of producing hemolysis in susceptible subjects and hepatocellular injury. The temporal proximity of drug ingestion and hemolysis, increased glucose utilization, lactate excess, and hepatic insufficiency suggests that nitrofurantoin may have been responisble for precipitating the clinical and chemical abnormalities observed."}
{"id": "PMID:12662", "title": "Effect of pH on ammonia production by renal mitochondria.", "content": "NH3 production by renal cortical mitochondria was studied under conditions of metabolic acidosis induced in vivo and with pH manipulations of the media bathing mitochondria from normal rats. A HCO3- medium equilibrated with O2 and CO2 was utilized with glutamine concentrations of either 10 or 0.5 mM. With chronic acidosis NH3 production increased significantly at either substrate concentration. Similar results were obtained with rotenone in the media, both with chronic acidosis and with acidosis of 3 h duration, indicating that increased glutamine entry and/or phosphate-dependent glutaminase (PDG) activity accounts for the increased ammoniagenesis. In contrast to acidosis induced in vivo, mitochondria from normal rats subjected to a diminution in medium pH, either by manipulation of HCO3 concentration or PCO2, significantly decrease NH3 production. Mitochondrial studies with rotenone, as well as studies of solubilized PDG, suggest that a low pH diminishes NH3 production by directly altering PDG activity. Furthermore, regardless of the specifics of the mechanism, these studies indicate that adaptation to metabolic acidosis is not the immediate, direct result of a change in pH.", "contents": "Effect of pH on ammonia production by renal mitochondria. NH3 production by renal cortical mitochondria was studied under conditions of metabolic acidosis induced in vivo and with pH manipulations of the media bathing mitochondria from normal rats. A HCO3- medium equilibrated with O2 and CO2 was utilized with glutamine concentrations of either 10 or 0.5 mM. With chronic acidosis NH3 production increased significantly at either substrate concentration. Similar results were obtained with rotenone in the media, both with chronic acidosis and with acidosis of 3 h duration, indicating that increased glutamine entry and/or phosphate-dependent glutaminase (PDG) activity accounts for the increased ammoniagenesis. In contrast to acidosis induced in vivo, mitochondria from normal rats subjected to a diminution in medium pH, either by manipulation of HCO3 concentration or PCO2, significantly decrease NH3 production. Mitochondrial studies with rotenone, as well as studies of solubilized PDG, suggest that a low pH diminishes NH3 production by directly altering PDG activity. Furthermore, regardless of the specifics of the mechanism, these studies indicate that adaptation to metabolic acidosis is not the immediate, direct result of a change in pH."}
{"id": "PMID:12658", "title": "Renal hemodynamics in drug-overdosed patients.", "content": "Effective renal plasms flow (ERPF) and glomerular filtration rate (GFR), as determined by a radioisotopic method, were evaluated in seven heroin-overdosage patients (Group I) and 7 hypnotic-sedative-analgesic overdosage patients (Group II). No patient had evidence of shock. There was no significant intergroup differences in PaO2, PaCO2, pH, blood pressure, pulse rate, respiratory rate, cardiac output, or serum creatinine levels. Group I patients had lower ERPF and GFR compared to Group II (271 +/- 182.8 vs. 580 +/- 62 cc/min and 62.4 +/- 32.6 vs. 102.9 +/- 12.8 cc/min, respectively, p less than 0.005). We conclude that compared to hypnotic-sedative-analagesic overdosed patients heroin overdosed patients heroin overdosed patients have more profoundly altered renal hemodynamics.", "contents": "Renal hemodynamics in drug-overdosed patients. Effective renal plasms flow (ERPF) and glomerular filtration rate (GFR), as determined by a radioisotopic method, were evaluated in seven heroin-overdosage patients (Group I) and 7 hypnotic-sedative-analgesic overdosage patients (Group II). No patient had evidence of shock. There was no significant intergroup differences in PaO2, PaCO2, pH, blood pressure, pulse rate, respiratory rate, cardiac output, or serum creatinine levels. Group I patients had lower ERPF and GFR compared to Group II (271 +/- 182.8 vs. 580 +/- 62 cc/min and 62.4 +/- 32.6 vs. 102.9 +/- 12.8 cc/min, respectively, p less than 0.005). We conclude that compared to hypnotic-sedative-analagesic overdosed patients heroin overdosed patients heroin overdosed patients have more profoundly altered renal hemodynamics."}
{"id": "PMID:12663", "title": "pH environmental of red cells in the spleen.", "content": "Intrasplenic pH in vivo was deduced from measurements on blood drained from cat spleen during contraction with the inflow occluded. The pH of blood in the red pulp is normally 7.20, but stasis or reduced flow through the pulp causes pH to fall toward 6.8. The splenic pulp contains blood of high hematocrit. To evaluate the role of buffering by the red cells themselves, intrasplenic p/ in red cell-free spleens was, therefore, estimated atering and leaving the spleen during red cell washout. At inflow pH less than 6.8 the outflow pH was raised, at inflow pH = 6.8 there was no change, b,t at inflow pH greater than 6.8 the outflow pH was lowered. These results indicate that the pH environment of red cells in the spleen results indicate that the pH environment of red cells in the spleen results from the interplay of two separate factors: i) pH-determining elements of the splenic tissue that buffer at 6.8, and ii) buffering provided by red cells passing through the pulp.", "contents": "pH environmental of red cells in the spleen. Intrasplenic pH in vivo was deduced from measurements on blood drained from cat spleen during contraction with the inflow occluded. The pH of blood in the red pulp is normally 7.20, but stasis or reduced flow through the pulp causes pH to fall toward 6.8. The splenic pulp contains blood of high hematocrit. To evaluate the role of buffering by the red cells themselves, intrasplenic p/ in red cell-free spleens was, therefore, estimated atering and leaving the spleen during red cell washout. At inflow pH less than 6.8 the outflow pH was raised, at inflow pH = 6.8 there was no change, b,t at inflow pH greater than 6.8 the outflow pH was lowered. These results indicate that the pH environment of red cells in the spleen results indicate that the pH environment of red cells in the spleen results from the interplay of two separate factors: i) pH-determining elements of the splenic tissue that buffer at 6.8, and ii) buffering provided by red cells passing through the pulp."}
{"id": "PMID:12664", "title": "Response to angiotensins I and II and to AI-converting-enzyme inhibitor in a shark.", "content": "The spiny dogfish shark, which does not have renal juxtaglomerular cells, exhibits a strong pressor response to both angiotensin I and II. A nonapeptide, angiotensin I-converting-enzyme inhibitor, blocks the pressor response to angiotensin I in this fish. The pressor response to both angiotensin II and norepinephrine is completely blocked by the adrenergic blocking drug phentolamine.", "contents": "Response to angiotensins I and II and to AI-converting-enzyme inhibitor in a shark. The spiny dogfish shark, which does not have renal juxtaglomerular cells, exhibits a strong pressor response to both angiotensin I and II. A nonapeptide, angiotensin I-converting-enzyme inhibitor, blocks the pressor response to angiotensin I in this fish. The pressor response to both angiotensin II and norepinephrine is completely blocked by the adrenergic blocking drug phentolamine."}
{"id": "PMID:12665", "title": "A comparison of high- and low-dose lorazepam with amylobarbitone in patients with anxiety states.", "content": "A double-blind crossover trial comparing lorazepam at two dosage levels with amylobarbitone supported previous reports of the effective anxiolytic action of the drug. Evaluation of the patients' responses during each week of treatment was based on a physician's weekly rating and on daily self-rating by patients. The results were analyzed by sequential and nonsequential analyses. The main side effect of the drug was drowsiness, which occurred to a clinically significant degree among the high-dose group of patients. The authors emphasize the value of two dosage trials, particularly in devising subsequent flexible individual treatment regimens.", "contents": "A comparison of high- and low-dose lorazepam with amylobarbitone in patients with anxiety states. A double-blind crossover trial comparing lorazepam at two dosage levels with amylobarbitone supported previous reports of the effective anxiolytic action of the drug. Evaluation of the patients' responses during each week of treatment was based on a physician's weekly rating and on daily self-rating by patients. The results were analyzed by sequential and nonsequential analyses. The main side effect of the drug was drowsiness, which occurred to a clinically significant degree among the high-dose group of patients. The authors emphasize the value of two dosage trials, particularly in devising subsequent flexible individual treatment regimens."}
{"id": "PMID:12666", "title": "Tardive dyskinesia: are first signs reversible?", "content": "Although tardive dyskinesia, a serious and sometimes irreversible side effect of antipsychotic drug use, is becoming increasingly common, there is still considerable confusion concerning the course of the syndrome. The authors observed 12 psychiatric patients with tardive dyskinesia from the inception of the syndrome. They found that first symptoms rarely persisted if antipsychotics were discontinued and concluded that the length of time symptoms have persisted prior to drug discontinuation, not age at onset, may be the major variable determining reversibility of the syndrome.", "contents": "Tardive dyskinesia: are first signs reversible? Although tardive dyskinesia, a serious and sometimes irreversible side effect of antipsychotic drug use, is becoming increasingly common, there is still considerable confusion concerning the course of the syndrome. The authors observed 12 psychiatric patients with tardive dyskinesia from the inception of the syndrome. They found that first symptoms rarely persisted if antipsychotics were discontinued and concluded that the length of time symptoms have persisted prior to drug discontinuation, not age at onset, may be the major variable determining reversibility of the syndrome."}
{"id": "PMID:12668", "title": "Timor filariasis: epidemiologic and clinical features in a defined community.", "content": "The epidemiology of Timor filariasis was observed during a clinical and parasitologic survey of persons living in a remote village on the island of Flores, Southeast Indonesia. Infection and disease was distributed evenly throughout the community, which was in accord with the breeding and feeding habits of the only identified vector, Anopheles barbirostris. Although micfofilaremia rates appeared independent of host variables of age and sexes and sex, symptoms of disease were greater among males than females, and in both sexes disease rates more than doubled between the first and second decades of life. Symptoms included recurring episodes of inguinal and femoral lymphadenitis with retrograde lymphangitis and fever, abscesses of lymph glands or vessels along the path of the great sapheneous vein and its mae highest yet reported for the Timor filaria; it is a virulent parasite causing serious ill-health among the inhabitants of eastern Flores.", "contents": "Timor filariasis: epidemiologic and clinical features in a defined community. The epidemiology of Timor filariasis was observed during a clinical and parasitologic survey of persons living in a remote village on the island of Flores, Southeast Indonesia. Infection and disease was distributed evenly throughout the community, which was in accord with the breeding and feeding habits of the only identified vector, Anopheles barbirostris. Although micfofilaremia rates appeared independent of host variables of age and sexes and sex, symptoms of disease were greater among males than females, and in both sexes disease rates more than doubled between the first and second decades of life. Symptoms included recurring episodes of inguinal and femoral lymphadenitis with retrograde lymphangitis and fever, abscesses of lymph glands or vessels along the path of the great sapheneous vein and its mae highest yet reported for the Timor filaria; it is a virulent parasite causing serious ill-health among the inhabitants of eastern Flores."}
{"id": "PMID:12669", "title": "Endemic eastern equine encephalomyelitis in Florida: a twenty-year analysis, 1955-1974.", "content": "Research and surveillance programs relating to the circulation of eastern equine encephalomyelitis (EEE) virus in Florida between 1955 and 1974 are summarized. All available data suggest that EEE virus is 1) endemic in many Florida fresh water swamps and waterways, 2) active in a continuous cycle throughout the year with a peak between May and August, and 3) circulating in Culiseta melanura. It has been isolated also from eight other mosquito species.", "contents": "Endemic eastern equine encephalomyelitis in Florida: a twenty-year analysis, 1955-1974. Research and surveillance programs relating to the circulation of eastern equine encephalomyelitis (EEE) virus in Florida between 1955 and 1974 are summarized. All available data suggest that EEE virus is 1) endemic in many Florida fresh water swamps and waterways, 2) active in a continuous cycle throughout the year with a peak between May and August, and 3) circulating in Culiseta melanura. It has been isolated also from eight other mosquito species."}
{"id": "PMID:12673", "title": "[Anesthetic considerations in patients with CAD (author's transl)].", "content": "The primary aim during anesthetic management of the patient with coronary artery disease is prevention of imbalance between myocardial oxygen supply and demand. Since oxygen supply is limited by restriction of coronary blood flow, prevention of increases in demand plus maintenance of supply, rather than increases in supply, will achieve this aim. The major determinants of myocardial oxygen demand are mechanical, i.e. (a) left ventricular wall tension, dependent in turn upon systolic pressure and ventricular volumn, (b) velocity of contraction, and (c) heart rate. Systolic pressure, pulmonary capillary wedge pressure, and heart rate monitoring will alert the anesthetist to increases associated with an enhanced oxygen demand. Decreased arterial diastolic and increased pulmonary capillary wedge pressure are associated with decreased supply. By appropriate manipulation of these variables and avoidance of episodes of myocardial ischemia, the perioperative morbidity and mortality rates associated with coronary artery disease may be decreased.", "contents": "[Anesthetic considerations in patients with CAD (author's transl)]. The primary aim during anesthetic management of the patient with coronary artery disease is prevention of imbalance between myocardial oxygen supply and demand. Since oxygen supply is limited by restriction of coronary blood flow, prevention of increases in demand plus maintenance of supply, rather than increases in supply, will achieve this aim. The major determinants of myocardial oxygen demand are mechanical, i.e. (a) left ventricular wall tension, dependent in turn upon systolic pressure and ventricular volumn, (b) velocity of contraction, and (c) heart rate. Systolic pressure, pulmonary capillary wedge pressure, and heart rate monitoring will alert the anesthetist to increases associated with an enhanced oxygen demand. Decreased arterial diastolic and increased pulmonary capillary wedge pressure are associated with decreased supply. By appropriate manipulation of these variables and avoidance of episodes of myocardial ischemia, the perioperative morbidity and mortality rates associated with coronary artery disease may be decreased."}
{"id": "PMID:12674", "title": "[Effect of combined application of halothane and some central depressants (author's transl)].", "content": "The combined effects of halothane and various central depressants were studied in mice by means of an isobolographic method which allows the statistical evaluation of interactions. A loss of the righting reflex for at least 2 min was taken as the criterion for the synchronisation of the peak time of drug effects. All interactions turned out to be supra-additive, more pronounced in the case of diazepam and flunitrazepam than in the case of medazepam, pentobarbitone or ethanol. The organic solvent used for the solution of diazepam and flunitrazepam was found to contribute to the observed interactions. The difficulties of estimating and classifying combined drug effects as well as their clinical relevance are discussed.", "contents": "[Effect of combined application of halothane and some central depressants (author's transl)]. The combined effects of halothane and various central depressants were studied in mice by means of an isobolographic method which allows the statistical evaluation of interactions. A loss of the righting reflex for at least 2 min was taken as the criterion for the synchronisation of the peak time of drug effects. All interactions turned out to be supra-additive, more pronounced in the case of diazepam and flunitrazepam than in the case of medazepam, pentobarbitone or ethanol. The organic solvent used for the solution of diazepam and flunitrazepam was found to contribute to the observed interactions. The difficulties of estimating and classifying combined drug effects as well as their clinical relevance are discussed."}
{"id": "PMID:12675", "title": "[Studies of the effects of an injectable combination of a local anaesthetic with a beta-receptor-blocker (author' transl)].", "content": "The use of an injectable combination of a local anaesthetic (Xylestesin) and a beta-receptor-blocker (Betadrenol) during maxillo-facial surgery is described in this paper. The statistical analysis of pulse and blood pressure recordings of 30 patients demonstrated no significant blood pressure changes; there was a significant decrease of the cardiac rate, however. It was noted that the negative chronotropic effect was the greater the higher the rate rate was before injection. The local anaesthetic described is of great therapeutic value, in particular for apprehensive patients and patients with tachycardia.", "contents": "[Studies of the effects of an injectable combination of a local anaesthetic with a beta-receptor-blocker (author' transl)]. The use of an injectable combination of a local anaesthetic (Xylestesin) and a beta-receptor-blocker (Betadrenol) during maxillo-facial surgery is described in this paper. The statistical analysis of pulse and blood pressure recordings of 30 patients demonstrated no significant blood pressure changes; there was a significant decrease of the cardiac rate, however. It was noted that the negative chronotropic effect was the greater the higher the rate rate was before injection. The local anaesthetic described is of great therapeutic value, in particular for apprehensive patients and patients with tachycardia."}
{"id": "PMID:12686", "title": "A unitary theory of anesthesia based on lateral phase separations in nerve membranes.", "content": "This paper relates research on anesthetic effects on lipid membrane systems to mechanisms of neural function. A unitary theory of anesthesia based on anesthetic-induced changes in fluid-solid-phase separations in the lipid region of nerve membranes is presented. It is suggested that anesthetics act by fluidizing nerve membranes to a point where critical lipid regions no longer contain phase separations. As a consequence, the membranes are less able to facilitate the conformational changes in proteins that may be the basis for such membrane events as ion gating, synaptic transmitter release, and transmitter binding to receptors. It is proposed that the anesthetic-modified phase separation behavior of the membrane may alter neural function by a combination of the following effects: inhibition of conformational changes of intrinsic membrane proteins; prevention of the association of protein subunits to form polymeric ion channels; depression of transmitter release by preventing fusion of vesicles containing synaptic transmitter with the membrane of the presynaptic terminal.", "contents": "A unitary theory of anesthesia based on lateral phase separations in nerve membranes. This paper relates research on anesthetic effects on lipid membrane systems to mechanisms of neural function. A unitary theory of anesthesia based on anesthetic-induced changes in fluid-solid-phase separations in the lipid region of nerve membranes is presented. It is suggested that anesthetics act by fluidizing nerve membranes to a point where critical lipid regions no longer contain phase separations. As a consequence, the membranes are less able to facilitate the conformational changes in proteins that may be the basis for such membrane events as ion gating, synaptic transmitter release, and transmitter binding to receptors. It is proposed that the anesthetic-modified phase separation behavior of the membrane may alter neural function by a combination of the following effects: inhibition of conformational changes of intrinsic membrane proteins; prevention of the association of protein subunits to form polymeric ion channels; depression of transmitter release by preventing fusion of vesicles containing synaptic transmitter with the membrane of the presynaptic terminal."}
{"id": "PMID:12687", "title": "[Apneic anesthesia in unventilated patients for various operations and explorations in laryngotracheal surgery].", "content": "A technique of anesthesia is considered for laryngoscopy in suspension, and certain acts of surgery of the vocal cords, e.g. myxoma, and of the trachea, e.g. destruction of papillomatosis. The patient is in apnea, unventilated, a catheter brings down to the level of the carena a current of oxygen of 15 liters per minute, the gaseous acidosis is buffered by injections of a solution of molar sodium bicarbonate. After briefly recalling the notions which justify this technique, its repercussion on homeostasis is studied by arterial gasometry. General anaesthesia with apneic oxygenation may offer the ENT surgeon increased possibilities of exploration and operation at the level of the larynx and trachea, but owing to its biological consequences, it should be used only with circumspection and its indications should be totally justified, for acts of limited duration. The technique seems, at present, difficult to adapt to surgery with laser.", "contents": "[Apneic anesthesia in unventilated patients for various operations and explorations in laryngotracheal surgery]. A technique of anesthesia is considered for laryngoscopy in suspension, and certain acts of surgery of the vocal cords, e.g. myxoma, and of the trachea, e.g. destruction of papillomatosis. The patient is in apnea, unventilated, a catheter brings down to the level of the carena a current of oxygen of 15 liters per minute, the gaseous acidosis is buffered by injections of a solution of molar sodium bicarbonate. After briefly recalling the notions which justify this technique, its repercussion on homeostasis is studied by arterial gasometry. General anaesthesia with apneic oxygenation may offer the ENT surgeon increased possibilities of exploration and operation at the level of the larynx and trachea, but owing to its biological consequences, it should be used only with circumspection and its indications should be totally justified, for acts of limited duration. The technique seems, at present, difficult to adapt to surgery with laser."}
{"id": "PMID:12688", "title": "[General anesthesia and bronchoscopy].", "content": "High frequency, positive pressure ventilation during anesthesia for bronchoscopy, uses the intermittent delivery of oxygen and an anesthetic gas mixture thus avoiding the risks of hypoxia, retention of carbon dioxide and concomitant acidosis. This technique may be used with low pressures in the airways (8 to 10 cm of water during insufflation).", "contents": "[General anesthesia and bronchoscopy]. High frequency, positive pressure ventilation during anesthesia for bronchoscopy, uses the intermittent delivery of oxygen and an anesthetic gas mixture thus avoiding the risks of hypoxia, retention of carbon dioxide and concomitant acidosis. This technique may be used with low pressures in the airways (8 to 10 cm of water during insufflation)."}
{"id": "PMID:12685", "title": "[Effects of naloxone on postoperative analgesia].", "content": "Two comparable groups of ten patients were studied. After nitrous oxide-oxygen fentanyl-pancuronium anesthesia, half the patients were reversed with a titrated dose of naloxone. Even in titrated doses naloxone rapidly abolished residual post-operative fentanyl analgesia in 80 p. 100 of the patients. In the control group none of the patients complained of pain for an average of six to eight hours. Blood gases in the recovery room were practically the same in reversed and non-reversed patients and were satisfactory.", "contents": "[Effects of naloxone on postoperative analgesia]. Two comparable groups of ten patients were studied. After nitrous oxide-oxygen fentanyl-pancuronium anesthesia, half the patients were reversed with a titrated dose of naloxone. Even in titrated doses naloxone rapidly abolished residual post-operative fentanyl analgesia in 80 p. 100 of the patients. In the control group none of the patients complained of pain for an average of six to eight hours. Blood gases in the recovery room were practically the same in reversed and non-reversed patients and were satisfactory."}
{"id": "PMID:12689", "title": "[Study of pressure and FeCO2 during ventilation by injection (preliminary note)].", "content": "This study, carried out in nine patients, attempted to judge the efficacy and possible inocuity of ventilation by injection (jet ventilation), firstly on capnography and. secondly, on recordings of intra-tracheal pressure. The frequency of six jets per minute, is that which, under the conditions of the trial, ensures the best removal of CO2 and the maintenance of stable CO2 levels in the trachea. Although pressures recorded in the airways varied between 15 and 40 torrs, the finding of very high peaks of pressure in certain cases, makes the authors somewhat reserved concerning the security of the method when the free reflux of gas is liable to be inhibited.", "contents": "[Study of pressure and FeCO2 during ventilation by injection (preliminary note)]. This study, carried out in nine patients, attempted to judge the efficacy and possible inocuity of ventilation by injection (jet ventilation), firstly on capnography and. secondly, on recordings of intra-tracheal pressure. The frequency of six jets per minute, is that which, under the conditions of the trial, ensures the best removal of CO2 and the maintenance of stable CO2 levels in the trachea. Although pressures recorded in the airways varied between 15 and 40 torrs, the finding of very high peaks of pressure in certain cases, makes the authors somewhat reserved concerning the security of the method when the free reflux of gas is liable to be inhibited."}
{"id": "PMID:12690", "title": "[Value of jet ventilation during otorhinolaryngologic endoscopies practiced under general anesthesia].", "content": "A technique of jet ventilation under general anesthesia (Alfaterinse suxamethonium) was used in 67 patients, in 55 cases for multiple endoscopic examinations in a single stage, usually laryngoscopy in suspension followed by oesophagoscopy, and in 12 cases, for an operation on the larynx. Arterial gasometry (PaO2 and PaCO2) proved the efficacy of the method, the major risk remaining, in the opinion of the authors, the possibility of excessive pressure which may be avoided by strict supervision.", "contents": "[Value of jet ventilation during otorhinolaryngologic endoscopies practiced under general anesthesia]. A technique of jet ventilation under general anesthesia (Alfaterinse suxamethonium) was used in 67 patients, in 55 cases for multiple endoscopic examinations in a single stage, usually laryngoscopy in suspension followed by oesophagoscopy, and in 12 cases, for an operation on the larynx. Arterial gasometry (PaO2 and PaCO2) proved the efficacy of the method, the major risk remaining, in the opinion of the authors, the possibility of excessive pressure which may be avoided by strict supervision."}
{"id": "PMID:12691", "title": "[Seeking an ideal protocol for the stability of blood gases during general anesthesia for bronchosopies].", "content": "During general anesthesia for bronchoscopy, hypoxemia is a major risk, especially in patients with a severe intrapulmonary shunt. With the technique of apnea in pure oxygen, after one hour denitrogentation, and with an intake of 50 liters of oxygen per minute through the bronchoscope, the PaO2 was greater than 400 mm of Hg, but hypercapnia and acidosis occurred. To compensate the latter, five minute sessions of apnea, alternating with two minutes of jet hyperventilation, nevertheless, have the disadvantage of producing a Ventrui phenomena at the proximal end of the bronchoscope, hence a fall in FiO2 which was dangerous in these high risk patients. The authors propose a method so that the Venturi phenomenon, which cannot be prevented, occurs in pure oxygen.", "contents": "[Seeking an ideal protocol for the stability of blood gases during general anesthesia for bronchosopies]. During general anesthesia for bronchoscopy, hypoxemia is a major risk, especially in patients with a severe intrapulmonary shunt. With the technique of apnea in pure oxygen, after one hour denitrogentation, and with an intake of 50 liters of oxygen per minute through the bronchoscope, the PaO2 was greater than 400 mm of Hg, but hypercapnia and acidosis occurred. To compensate the latter, five minute sessions of apnea, alternating with two minutes of jet hyperventilation, nevertheless, have the disadvantage of producing a Ventrui phenomena at the proximal end of the bronchoscope, hence a fall in FiO2 which was dangerous in these high risk patients. The authors propose a method so that the Venturi phenomenon, which cannot be prevented, occurs in pure oxygen."}
{"id": "PMID:12692", "title": "[General anesthesia for bronchoscopy and lipidol bronchography in children and infants].", "content": "In 160 cases of children and infants, a technique of general anesthesia is described (penthiobarbital-suxamethonium, then halothane-oxygen with a mask in spontaneous ventilation if the bronchoscopy is followed by lipiodol bronchography). This technique is simple and efficacious and makes the child comfortable, especially in cases of repeated operation, and for the operator whose gestures are more rapid and less traumatising and this permits rapid awakening. No incidents or severe complications were noted.", "contents": "[General anesthesia for bronchoscopy and lipidol bronchography in children and infants]. In 160 cases of children and infants, a technique of general anesthesia is described (penthiobarbital-suxamethonium, then halothane-oxygen with a mask in spontaneous ventilation if the bronchoscopy is followed by lipiodol bronchography). This technique is simple and efficacious and makes the child comfortable, especially in cases of repeated operation, and for the operator whose gestures are more rapid and less traumatising and this permits rapid awakening. No incidents or severe complications were noted."}
{"id": "PMID:12693", "title": "[Salvage of a patient with respiratory distress caused by tracheal obstruction, by use of a Fogarty catheter].", "content": "The author observed a state of acute asphyxia due to a mucosal plug in a patient undergoing total laryngectomy. After failure of classical methods of removal and the plug and in view of the critical state of the patient, a heroic procedure was used: extraction of the mucosal plug using a Fogarty catheter, as used in arterial surgery.", "contents": "[Salvage of a patient with respiratory distress caused by tracheal obstruction, by use of a Fogarty catheter]. The author observed a state of acute asphyxia due to a mucosal plug in a patient undergoing total laryngectomy. After failure of classical methods of removal and the plug and in view of the critical state of the patient, a heroic procedure was used: extraction of the mucosal plug using a Fogarty catheter, as used in arterial surgery."}
{"id": "PMID:12694", "title": "[Choice of anesthesia technic for suspension larygoscopy].", "content": "Anesthesia, during suspension laryngoscopy should permit the ENT surgeon to work in a field without the hindrance of an intra-tracheal tube, and with a calm larynx. After rapid review of anesthesias of brief duration, which are eliminated, several techniques of anesthesia  of variable duration are discussed. Neuroleptanalgesia is nevertheless exclused owing to the environmental conditions necessary for its use. Gamma OH was reserved for patients in poor general health, and gave satisfaction. Alfatisine was used here and procured anesthesia of good quality, with minimal respiratory depression, provided a precise protocol is respected, but one cannot hope for success of suspension laryngoscopy without local anesthesia in addition.", "contents": "[Choice of anesthesia technic for suspension larygoscopy]. Anesthesia, during suspension laryngoscopy should permit the ENT surgeon to work in a field without the hindrance of an intra-tracheal tube, and with a calm larynx. After rapid review of anesthesias of brief duration, which are eliminated, several techniques of anesthesia  of variable duration are discussed. Neuroleptanalgesia is nevertheless exclused owing to the environmental conditions necessary for its use. Gamma OH was reserved for patients in poor general health, and gave satisfaction. Alfatisine was used here and procured anesthesia of good quality, with minimal respiratory depression, provided a precise protocol is respected, but one cannot hope for success of suspension laryngoscopy without local anesthesia in addition."}
{"id": "PMID:12695", "title": "[Bronchoscopies under Alfatesine].", "content": "Alfatesine in perfusion, associated with laryngo-tracheal local anesthesia, was used to carry out 131 bronchoscopies. The comfort of the patient and of the bronchoscopist were then assessed. A few cardio-vascular side-effects, e.g. severe hypotension in two cases, hypertensive effects and tachycardia during introduction of the bornchoscope, were noted.", "contents": "[Bronchoscopies under Alfatesine]. Alfatesine in perfusion, associated with laryngo-tracheal local anesthesia, was used to carry out 131 bronchoscopies. The comfort of the patient and of the bronchoscopist were then assessed. A few cardio-vascular side-effects, e.g. severe hypotension in two cases, hypertensive effects and tachycardia during introduction of the bornchoscope, were noted."}
{"id": "PMID:12696", "title": "[Severe asphyxiant hemoptysis. Bronchoscopy under extracorporeal circulation].", "content": "The authors report a case of bronchoscopy made necessary by severe hemoptysis in a young man with very severe respiratory distress. Bronchoscopy was carried out under excellent conditions thanks to respiratory assistance supplied by partial femoro-femoral extra-corporeal circulation. The interest and limits of this method are discussed.", "contents": "[Severe asphyxiant hemoptysis. Bronchoscopy under extracorporeal circulation]. The authors report a case of bronchoscopy made necessary by severe hemoptysis in a young man with very severe respiratory distress. Bronchoscopy was carried out under excellent conditions thanks to respiratory assistance supplied by partial femoro-femoral extra-corporeal circulation. The interest and limits of this method are discussed."}
{"id": "PMID:12697", "title": "[Anesthesia during resections-anastomoses of the trachea and tracheal bifurcation. Apropos of 4 cases].", "content": "The author reports 4 cases of surgery of the lower trachea and of tracheal bifurcation, and consider: -that it is preferable only to intervene after improvement by medical treatment of the phase of acute asphyxia; -that a technique of general anesthesia, with deep curarisation and oro-tracheal catheter placed above the stenosis, permits correct ventilation; -that in cases of impossibility of ventilation, one should use extra-corporeal circulation, which should always be provided for.", "contents": "[Anesthesia during resections-anastomoses of the trachea and tracheal bifurcation. Apropos of 4 cases]. The author reports 4 cases of surgery of the lower trachea and of tracheal bifurcation, and consider: -that it is preferable only to intervene after improvement by medical treatment of the phase of acute asphyxia; -that a technique of general anesthesia, with deep curarisation and oro-tracheal catheter placed above the stenosis, permits correct ventilation; -that in cases of impossibility of ventilation, one should use extra-corporeal circulation, which should always be provided for."}
{"id": "PMID:12698", "title": "[Prevention of tracheal lesions by rhythmic insufflation of the intubation catheter ballone].", "content": "The prevention of tracheal lesions due to the ballons of the intubation catheters depends on the correction of several factors concerning: -the material used (polyvinyl is better tolerated than rubber); -the shape (the sleeve-shape balloons are less traumatic); -the pressure of use, which should remain moderate; -the permanence of the compression (one should use intermittent filling of the ballon). A device designed by the authors and which is described here, permits intermittent insufflation of the ballons of the endotracheal catheters, by adaptation of certain apparatus of artificial ventilation, type LOGIC and SF4, has given excellent results.", "contents": "[Prevention of tracheal lesions by rhythmic insufflation of the intubation catheter ballone]. The prevention of tracheal lesions due to the ballons of the intubation catheters depends on the correction of several factors concerning: -the material used (polyvinyl is better tolerated than rubber); -the shape (the sleeve-shape balloons are less traumatic); -the pressure of use, which should remain moderate; -the permanence of the compression (one should use intermittent filling of the ballon). A device designed by the authors and which is described here, permits intermittent insufflation of the ballons of the endotracheal catheters, by adaptation of certain apparatus of artificial ventilation, type LOGIC and SF4, has given excellent results."}
{"id": "PMID:12699", "title": "[A rational naso-tracheal catheter].", "content": "For the last 4 years, the author has been using, especially for oral surgery, a naso-tracheal catheter (Rosso catheter), the intra-facial part of which has an S-shape which follows the curves of the airway and the outer part of which, in reinforced latex, permits attachment to the face and easy, reliable connection to the anesthetic apparatus. This catheter is easy to introduce, keeps well in place and frees perfectly the operative field and gives the anesthetist satisfactory mastery of the patient's ventilation.", "contents": "[A rational naso-tracheal catheter]. For the last 4 years, the author has been using, especially for oral surgery, a naso-tracheal catheter (Rosso catheter), the intra-facial part of which has an S-shape which follows the curves of the airway and the outer part of which, in reinforced latex, permits attachment to the face and easy, reliable connection to the anesthetic apparatus. This catheter is easy to introduce, keeps well in place and frees perfectly the operative field and gives the anesthetist satisfactory mastery of the patient's ventilation."}
{"id": "PMID:12700", "title": "[Difficult intubations in anesthesia].", "content": "The authors  present six cases of difficult intubation and review the literature on this subject; The circumstances during which difficult intubation may be feared are recalled; some are due to the morphology of the subject, the others to his previous pathology which may be rheumatological or dermatological. The authors then discuss the method of anaesthesia for this unusual intubation and the various technical means proposed to carry out safely the intubation itself.", "contents": "[Difficult intubations in anesthesia]. The authors  present six cases of difficult intubation and review the literature on this subject; The circumstances during which difficult intubation may be feared are recalled; some are due to the morphology of the subject, the others to his previous pathology which may be rheumatological or dermatological. The authors then discuss the method of anaesthesia for this unusual intubation and the various technical means proposed to carry out safely the intubation itself."}
{"id": "PMID:12701", "title": "[Difficult intubations and proposed solutions. Intubation by fiberscopy].", "content": "After a review of the various techniques used in difficult intubations, the authors emphasize recent progress in the field of fiber endoscopy. The advantages of this technique, e.g. absence of trauma, increased field of exploration and reduction in dose of anaesthetic drugs, exceed the present disadvantages, e.g. high price of this material, relatively fragile apparatus, too long and diameter too great for use in children.", "contents": "[Difficult intubations and proposed solutions. Intubation by fiberscopy]. After a review of the various techniques used in difficult intubations, the authors emphasize recent progress in the field of fiber endoscopy. The advantages of this technique, e.g. absence of trauma, increased field of exploration and reduction in dose of anaesthetic drugs, exceed the present disadvantages, e.g. high price of this material, relatively fragile apparatus, too long and diameter too great for use in children."}
{"id": "PMID:12702", "title": "[Use of closed circuit television for teaching tracheal intubation to medical students].", "content": "There are many occassions when patients could benefit from early intubation. This skill should be acquired by all doctors and not only by resuscitators and trainee anaesthetists. In Liverpool, all undergraduates in their fifth year of medicine are expected to intubate a minimum of ten patients lnder supervision of the anaesthetist. The use of closed circuit television has been explored and its value assessed in the teaching of intubation to undergraduates. The availability of hardware that is inexpensive, relatively simple to use and requiring minimal staff, such as Phikips VCR N1500 has made this approach to all. Videotapes are superior to film for this, since they are cheap, reusable and do not require chemical processing. The medium is versatile and replay immediate. Student performance can be recorded and replayed to allow positive identification of an imperfect technique. The videotape permits discussion and demonstration of methods of improvement of technique. A pre-recorded tape can be used to illustrate the anatomy and to demonstrate intubation in the absence of a patient. The fact that this is in black and white at the moment may be a disadvantage, but colour is not essential for recognition of the anatomy of the larynx. It must not be forgotten that in Britain, written permission is required before recording patients on \"videograms\". This can be obtained by modification of the consent forms signed by the patients prior to surgery.", "contents": "[Use of closed circuit television for teaching tracheal intubation to medical students]. There are many occassions when patients could benefit from early intubation. This skill should be acquired by all doctors and not only by resuscitators and trainee anaesthetists. In Liverpool, all undergraduates in their fifth year of medicine are expected to intubate a minimum of ten patients lnder supervision of the anaesthetist. The use of closed circuit television has been explored and its value assessed in the teaching of intubation to undergraduates. The availability of hardware that is inexpensive, relatively simple to use and requiring minimal staff, such as Phikips VCR N1500 has made this approach to all. Videotapes are superior to film for this, since they are cheap, reusable and do not require chemical processing. The medium is versatile and replay immediate. Student performance can be recorded and replayed to allow positive identification of an imperfect technique. The videotape permits discussion and demonstration of methods of improvement of technique. A pre-recorded tape can be used to illustrate the anatomy and to demonstrate intubation in the absence of a patient. The fact that this is in black and white at the moment may be a disadvantage, but colour is not essential for recognition of the anatomy of the larynx. It must not be forgotten that in Britain, written permission is required before recording patients on \"videograms\". This can be obtained by modification of the consent forms signed by the patients prior to surgery."}
{"id": "PMID:12703", "title": "[Problems posed by difficult intubations].", "content": "The difficulties of tracheal intubation are mainly encountered in facial surgery and E.N.T.  surgery, but they may nevertheless, occur in any form of surgery. The indications for nasal intubation, without visible glottis, the problems raised and the means of solving them, whilst respecting safety precautions, are briefly recalled.", "contents": "[Problems posed by difficult intubations]. The difficulties of tracheal intubation are mainly encountered in facial surgery and E.N.T.  surgery, but they may nevertheless, occur in any form of surgery. The indications for nasal intubation, without visible glottis, the problems raised and the means of solving them, whilst respecting safety precautions, are briefly recalled."}
{"id": "PMID:12704", "title": "[Difficult intubations].", "content": "The author reports twelve cases of difficult tracheal intubation, sometimes in acrobatic conditions, in victims of railway accidents. The position of the patient, the circumstances of the accident and the importance of the ventilatory distress, make tracheal intubation essential \"in situ\". The success of this act depends on the qualification of the medical and para-medical personnel, the technique proposed and the choice of material used.", "contents": "[Difficult intubations]. The author reports twelve cases of difficult tracheal intubation, sometimes in acrobatic conditions, in victims of railway accidents. The position of the patient, the circumstances of the accident and the importance of the ventilatory distress, make tracheal intubation essential \"in situ\". The success of this act depends on the qualification of the medical and para-medical personnel, the technique proposed and the choice of material used."}
{"id": "PMID:12705", "title": "[Sterilization of intratracheal tubes].", "content": "After a brief review of classical and modern methods of sterilisation of endo-tracheal catheters, where they emphasize the dangers of the use of ethylene oxide, the authors recall the common procedure which they used: washing with water and soap, and soaking for 6 to 7 hours in formaldehyde or in a solution of quaternary ammonium salts, and all manipulations should be made using gloves.", "contents": "[Sterilization of intratracheal tubes]. After a brief review of classical and modern methods of sterilisation of endo-tracheal catheters, where they emphasize the dangers of the use of ethylene oxide, the authors recall the common procedure which they used: washing with water and soap, and soaking for 6 to 7 hours in formaldehyde or in a solution of quaternary ammonium salts, and all manipulations should be made using gloves."}
{"id": "PMID:12706", "title": "[Laryngo-tracheal stenoses after intubation during resuscitation (notes apropos of a series of complications)].", "content": "The authors observed an abnormal frequency of laryngo-tracheal stenosis over a period of three months, corresponding to the use of a defective lot of supple catheters for single use and made of polyvinyl chloride. They emphasize the extreme difficulty to demonstrate the precise etiology of these severe complications.", "contents": "[Laryngo-tracheal stenoses after intubation during resuscitation (notes apropos of a series of complications)]. The authors observed an abnormal frequency of laryngo-tracheal stenosis over a period of three months, corresponding to the use of a defective lot of supple catheters for single use and made of polyvinyl chloride. They emphasize the extreme difficulty to demonstrate the precise etiology of these severe complications."}
{"id": "PMID:12707", "title": "[Complications during use of the Carlens catheter].", "content": "Two complications occurring during anesthesia with the use of Carlens catheter are discribed: -in the first case, perforation of the carena by the tip of the catheter and a tear along that left main bronchus, owing to invasion of the area by carcinoma, and death on the second post-operative day in spite of sutures that were carried out. -in the second case, poor indications for selective intubation of the left main bronchus by left upper lobectomy initially foreseen, whereas pneumonectomy was necessary, hypoventilation, anoxia, cardiac inefficacy.", "contents": "[Complications during use of the Carlens catheter]. Two complications occurring during anesthesia with the use of Carlens catheter are discribed: -in the first case, perforation of the carena by the tip of the catheter and a tear along that left main bronchus, owing to invasion of the area by carcinoma, and death on the second post-operative day in spite of sutures that were carried out. -in the second case, poor indications for selective intubation of the left main bronchus by left upper lobectomy initially foreseen, whereas pneumonectomy was necessary, hypoventilation, anoxia, cardiac inefficacy."}
{"id": "PMID:12708", "title": "[Glycosyltranferases. Biological and pathological importance].", "content": "Catalysing the transfer of oses and ose derivatives on various accepters, glucosyltransferases are of increasing importance in biology and pathology. Their sub-cellular localisation is now known together with the physico-chemical parameters of their activity and the importance of polyprenic intermediates. The first phenomenological studies concerning them are in favour of a mechanism of Bi-Bi type. For example, they may play a role in mucoviscidosis, virus diseases, vaccination and arthrosis.", "contents": "[Glycosyltranferases. Biological and pathological importance]. Catalysing the transfer of oses and ose derivatives on various accepters, glucosyltransferases are of increasing importance in biology and pathology. Their sub-cellular localisation is now known together with the physico-chemical parameters of their activity and the importance of polyprenic intermediates. The first phenomenological studies concerning them are in favour of a mechanism of Bi-Bi type. For example, they may play a role in mucoviscidosis, virus diseases, vaccination and arthrosis."}
{"id": "PMID:12713", "title": "Effect of beta-blockade during bowling competitions.", "content": "Seventeen amateur bowlers taking part in local bowling competitions were given either 40 mg of oxprenolol or placebo before the competitions, so that each subject played two competitions on oxprenolol and two on placebo in random order. All the bowlers had a relative tachycardia 15 min before the competition which was abolished by oxprenolol. A similar reduction in the heart rate during and after the compeptition was likewise seen after oxprenolol. The drug caused only minor changes in the systolic blood pressure in comparision with placebo. On the whole, the total scores of placebo and oxprenolol competitions did not differ significantly from each other, nor was there any difference between the scores of the trial competitions and the average results during previous season. However, when the bowlers were divided into subgroups according to the effect exerted by oxprenolol on performance, about one third of the bowlers did benefit from the oxprenolol treatment while 50% had worse results. The bowlers whose bowling performance was improved by oxprenolol exhibited significantly higher heart rates before, during and after the competition as compared with the subgroups not responding beneficially to the active drug. The effect of oxprenolol was most pronounced during the very first series and the harmful effect of the drug was mainly seen in the last series of the competition. One reason for the impairment of the general performance could conceivably be an \"overrelaxed\" state as indicated by the greater number of misses made by the bowlers when treated with oxprenolol.", "contents": "Effect of beta-blockade during bowling competitions. Seventeen amateur bowlers taking part in local bowling competitions were given either 40 mg of oxprenolol or placebo before the competitions, so that each subject played two competitions on oxprenolol and two on placebo in random order. All the bowlers had a relative tachycardia 15 min before the competition which was abolished by oxprenolol. A similar reduction in the heart rate during and after the compeptition was likewise seen after oxprenolol. The drug caused only minor changes in the systolic blood pressure in comparision with placebo. On the whole, the total scores of placebo and oxprenolol competitions did not differ significantly from each other, nor was there any difference between the scores of the trial competitions and the average results during previous season. However, when the bowlers were divided into subgroups according to the effect exerted by oxprenolol on performance, about one third of the bowlers did benefit from the oxprenolol treatment while 50% had worse results. The bowlers whose bowling performance was improved by oxprenolol exhibited significantly higher heart rates before, during and after the competition as compared with the subgroups not responding beneficially to the active drug. The effect of oxprenolol was most pronounced during the very first series and the harmful effect of the drug was mainly seen in the last series of the competition. One reason for the impairment of the general performance could conceivably be an \"overrelaxed\" state as indicated by the greater number of misses made by the bowlers when treated with oxprenolol."}
{"id": "PMID:12714", "title": "The role of microsomal cytochrome b5 in the metabolism of ethanol, drugs and the desaturation of fatty acids.", "content": "Liver endoplasmic membrane contains two hemoproteins, cyt. P-450 and cyt. b5. Cytochrome P-450 catalyzes the hydroxylation of lipid-soluble compounds, while the cyt. b5 system is involved in desaturation of fatty acids. NAD(P)H and oxygen are essential components for both systems. Oxidation of ethanol to acetate in the liver, via alcohol and acetaldehyde dehydrogenases, leads to an elevated cellular NADH content. It has been proposed that oxidation of the cytosolic NADH occurs predominantly in the mitochondria via the substrate oxidation-reduction shuttle. In order to investigate the effects of elevated levels of cytosolic NADH on the state of the endoplasmic hemoprotein system, microsomes from a fatty human liver (post-ethanol intake) were isolated and studied. Microsomal cyt. b5 reductase was found to reoxidize cytoplasmic NADH directly and transfer the reducing equivalents readily to the microsomal oxidases. Addition of catalytic amounts of alcohol dehydrogenase, NAD, and ethanol to microsomes resulted in a rapid reduction of microsomal cyt. b5. These results are consistent with the proposal that the catalytic moiety of cyt. b5 reductase is exposed to the aqueous phase of the membrane and directly accepts reducing equivalents from the cytoplasm. Microsomes from fatty human liver showed an increased rate of cyt. b5 dependent desaturation of fatty acids. These findings suggest that ethanol metabolism may selectively affect the activity of one or the other microsomal hemoprotein. Thus, when the desaturase activity is low, drug metabolism by the cyt. P-450 pathway may predominate. Conversely, an increase in the desaturase level may lead to a decreased drug metabolism. This mechanism may underlie the clinical observations of drug intolerance reactions associated with alcohol intake.", "contents": "The role of microsomal cytochrome b5 in the metabolism of ethanol, drugs and the desaturation of fatty acids. Liver endoplasmic membrane contains two hemoproteins, cyt. P-450 and cyt. b5. Cytochrome P-450 catalyzes the hydroxylation of lipid-soluble compounds, while the cyt. b5 system is involved in desaturation of fatty acids. NAD(P)H and oxygen are essential components for both systems. Oxidation of ethanol to acetate in the liver, via alcohol and acetaldehyde dehydrogenases, leads to an elevated cellular NADH content. It has been proposed that oxidation of the cytosolic NADH occurs predominantly in the mitochondria via the substrate oxidation-reduction shuttle. In order to investigate the effects of elevated levels of cytosolic NADH on the state of the endoplasmic hemoprotein system, microsomes from a fatty human liver (post-ethanol intake) were isolated and studied. Microsomal cyt. b5 reductase was found to reoxidize cytoplasmic NADH directly and transfer the reducing equivalents readily to the microsomal oxidases. Addition of catalytic amounts of alcohol dehydrogenase, NAD, and ethanol to microsomes resulted in a rapid reduction of microsomal cyt. b5. These results are consistent with the proposal that the catalytic moiety of cyt. b5 reductase is exposed to the aqueous phase of the membrane and directly accepts reducing equivalents from the cytoplasm. Microsomes from fatty human liver showed an increased rate of cyt. b5 dependent desaturation of fatty acids. These findings suggest that ethanol metabolism may selectively affect the activity of one or the other microsomal hemoprotein. Thus, when the desaturase activity is low, drug metabolism by the cyt. P-450 pathway may predominate. Conversely, an increase in the desaturase level may lead to a decreased drug metabolism. This mechanism may underlie the clinical observations of drug intolerance reactions associated with alcohol intake."}
{"id": "PMID:12715", "title": "Kinetics of the conformational changes of hemopexin in acid media.", "content": "Under the action of acid media the hemopexin molecule unfolds with resulting heme expulsion from the binding site, followed by heme dimerization and reassociation of dimeric heme with the unfolded protein molecule. The rate of the reaction is pH dependent and the whole process is fully reversible for a certain time interval. Prolonged treatment of hemopexin at acidic conditions, however, leads to the irreversible denaturation of this protein.", "contents": "Kinetics of the conformational changes of hemopexin in acid media. Under the action of acid media the hemopexin molecule unfolds with resulting heme expulsion from the binding site, followed by heme dimerization and reassociation of dimeric heme with the unfolded protein molecule. The rate of the reaction is pH dependent and the whole process is fully reversible for a certain time interval. Prolonged treatment of hemopexin at acidic conditions, however, leads to the irreversible denaturation of this protein."}
{"id": "PMID:12717", "title": "Comparative in vitro studies of cinoxacin, nalidixic acid, and oxolinic acid.", "content": "Cinoxacin and nalidixic acid were found to be similar in in vitro activity against 138 Shigella isolates and somewhat less active than oxolinic acid on a weight basis. Cross-resistance developed when 10 shigellae were transferred on increasing amounts of the respective agent contained in Mueller-Hinton agar. Plate dilution studies of the effect of changes in agar pH on the minimum inhibitory concentration revealed that the antibacterial activity increased with decreasing pH. Protein binding investigations revealed a high degree of binding, with nalidixic acid > oxolinic acid > cinoxacin.", "contents": "Comparative in vitro studies of cinoxacin, nalidixic acid, and oxolinic acid. Cinoxacin and nalidixic acid were found to be similar in in vitro activity against 138 Shigella isolates and somewhat less active than oxolinic acid on a weight basis. Cross-resistance developed when 10 shigellae were transferred on increasing amounts of the respective agent contained in Mueller-Hinton agar. Plate dilution studies of the effect of changes in agar pH on the minimum inhibitory concentration revealed that the antibacterial activity increased with decreasing pH. Protein binding investigations revealed a high degree of binding, with nalidixic acid > oxolinic acid > cinoxacin."}
{"id": "PMID:12718", "title": "Production of an extracellular maltase by thermophilic Bacillus sp. KP 1035.", "content": "Production of extracellular maltase was studied with thermophilic Bacillus sp. KP 1035, which was selected as the organism producing the highest levels of maltase. The final enzyme yield was increased by maltose, peptone, and yeast extract but reduced by succinate and fumarate. Maximum enzyme production was achieved at 55 degrees C and at an initial pH of 6.2 to 7.0 on a medium containing 0.3% maltose, 1% peptone, 0.1% meat extract, 0.3% yeast extract, 0.3% KH2PO4, and 0.1% KH2PO4. Maltase was synthesized in cytoplasm and accumulated as a large pool during the logarithmic growth phase, which preceded sporulation. At the end of this phase, the enzyme appeared in the culture broth, and its accumulation increased in parallel with a rise in the extracellular protein level. Maltase was stable for 24 h at 60 degrees C over a pH range of 5.6 to 9.0 and retained 95% of the original activity after treatment for 20 min at 70 degrees C at pH 6.8.", "contents": "Production of an extracellular maltase by thermophilic Bacillus sp. KP 1035. Production of extracellular maltase was studied with thermophilic Bacillus sp. KP 1035, which was selected as the organism producing the highest levels of maltase. The final enzyme yield was increased by maltose, peptone, and yeast extract but reduced by succinate and fumarate. Maximum enzyme production was achieved at 55 degrees C and at an initial pH of 6.2 to 7.0 on a medium containing 0.3% maltose, 1% peptone, 0.1% meat extract, 0.3% yeast extract, 0.3% KH2PO4, and 0.1% KH2PO4. Maltase was synthesized in cytoplasm and accumulated as a large pool during the logarithmic growth phase, which preceded sporulation. At the end of this phase, the enzyme appeared in the culture broth, and its accumulation increased in parallel with a rise in the extracellular protein level. Maltase was stable for 24 h at 60 degrees C over a pH range of 5.6 to 9.0 and retained 95% of the original activity after treatment for 20 min at 70 degrees C at pH 6.8."}
{"id": "PMID:12719", "title": "Virus inactivation by grapes and wines.", "content": "Infusions and extracts of different grapes inactivated poliovirus; agents responsible for this property resided in the skin of the grape. Commercial grape juice at both natural and neutral pH inactivate various enteric viruses and herpes simplex virus; a 1,000-fold reduction in poliovirus infectivity occurred after incubation with grape juice, pH 7.0, for 24 h at 4 degrees C. A variety of wines were antiviral but to a lesser extent than grape juice; red wines were more antiviral than white. Antiviral activity was demonstrable in fractions of grape juice varying in molecular weight from less than 1,000 to greater than 30,000 as determined by membrane filtration. Some restoration of poliovirus infectivity from virus-grape juice complexes was achieved with 1% gelatin, 0.1% Tween 80, 0.5% polyvinyl pyrrolidone, and 0.5% polyethylene glycol.", "contents": "Virus inactivation by grapes and wines. Infusions and extracts of different grapes inactivated poliovirus; agents responsible for this property resided in the skin of the grape. Commercial grape juice at both natural and neutral pH inactivate various enteric viruses and herpes simplex virus; a 1,000-fold reduction in poliovirus infectivity occurred after incubation with grape juice, pH 7.0, for 24 h at 4 degrees C. A variety of wines were antiviral but to a lesser extent than grape juice; red wines were more antiviral than white. Antiviral activity was demonstrable in fractions of grape juice varying in molecular weight from less than 1,000 to greater than 30,000 as determined by membrane filtration. Some restoration of poliovirus infectivity from virus-grape juice complexes was achieved with 1% gelatin, 0.1% Tween 80, 0.5% polyvinyl pyrrolidone, and 0.5% polyethylene glycol."}
{"id": "PMID:12716", "title": "Kinetics and biochemical properties of haemopoietic stem cells during chicken development.", "content": "Haemopoietic stem cells from donors of different ages (embryos, adults) have been grafted into irradiated hosts. Cell multiplication kinetics, foetal haemoglobin production, age-specific antigen production were examined during two weeks after grafting. The results obtained tend to show that the erythrocyte characteristics are, for a large part, already determined in a stem cell type endowed with a large proliferative capacity.", "contents": "Kinetics and biochemical properties of haemopoietic stem cells during chicken development. Haemopoietic stem cells from donors of different ages (embryos, adults) have been grafted into irradiated hosts. Cell multiplication kinetics, foetal haemoglobin production, age-specific antigen production were examined during two weeks after grafting. The results obtained tend to show that the erythrocyte characteristics are, for a large part, already determined in a stem cell type endowed with a large proliferative capacity."}
{"id": "PMID:12720", "title": "Bacterial fermentation of cheese whey for production of a ruminant feed supplement rich in curde protein.", "content": "A simple and efficient process for the production of a ruminant feed supplement, rich in crude protein (defined as total N X 6.25), by bacterial fermentation of cheese whey has been developed. The lactose in unpasteurized whey is fermented to lactate acid by Lactobacillus bulgaricus at a temperature of 43 degrees C and pH 5.5. The lactic acid produced is continually neutralized with ammonia to form ammonium lactate. The fermented product is concentrated by evaporation to a solids content of about 70% and adjusted to pH 6.8 with additional ammonia. The concentrated product contains about 55% crude protein. Approximately 6 to 8% of the crude protein is derived from bacterial cells. 17% from whey proteins, and 75 to 77% from ammonium lactate. The efficiency of conversion of lactose to lactic acid usually exceeds 95%. The fermentation time is greatly reduced upon the addition of 0.2% yeast extract or 0.1% corn steep liquor as a source of growth factors. Whey containing lactose at concentrations up to 7% can be fermented efficiently, but at higher concentrations lactose is fermented incompletely. The process has been scaled up to a pilot plant level, and 40 tons of concentrated product were produced fro animal feeding trials, without ever encountering putrefactive spoilage.", "contents": "Bacterial fermentation of cheese whey for production of a ruminant feed supplement rich in curde protein. A simple and efficient process for the production of a ruminant feed supplement, rich in crude protein (defined as total N X 6.25), by bacterial fermentation of cheese whey has been developed. The lactose in unpasteurized whey is fermented to lactate acid by Lactobacillus bulgaricus at a temperature of 43 degrees C and pH 5.5. The lactic acid produced is continually neutralized with ammonia to form ammonium lactate. The fermented product is concentrated by evaporation to a solids content of about 70% and adjusted to pH 6.8 with additional ammonia. The concentrated product contains about 55% crude protein. Approximately 6 to 8% of the crude protein is derived from bacterial cells. 17% from whey proteins, and 75 to 77% from ammonium lactate. The efficiency of conversion of lactose to lactic acid usually exceeds 95%. The fermentation time is greatly reduced upon the addition of 0.2% yeast extract or 0.1% corn steep liquor as a source of growth factors. Whey containing lactose at concentrations up to 7% can be fermented efficiently, but at higher concentrations lactose is fermented incompletely. The process has been scaled up to a pilot plant level, and 40 tons of concentrated product were produced fro animal feeding trials, without ever encountering putrefactive spoilage."}
{"id": "PMID:12721", "title": "Growth of Aureobasidium pullulans on straw hydrolysate.", "content": "Growth characteristics and cell properties of Aureobasidium (Pullularia) pullulans were studied. The organism grew well on an acid hydrolysate of ryegrass straw over a wide range of pH and temperature. The optimum temperature and pH for the growth of the organism were 32 degrees C and 5.5, respectively. A cell yield of 1.5 g/liter of straw hydrolysate was obtained. The dried cell mass contained 42.6% crude protein, 0.4% crude fat, and 6.4% nucleic acids. The essential amino acid profile of the microbial protein was comparable to that of Candida utilis. A rat feeding study indicated that the A. pullulans cells were not toxic and that the feed intake, weight gain, and protein efficiency ratio values were superior to those obtained with C. utilis. Once the question of mathogenicity is resolved, A. pullulans could be useful for production of single-cell protein from cellulosic wastes.", "contents": "Growth of Aureobasidium pullulans on straw hydrolysate. Growth characteristics and cell properties of Aureobasidium (Pullularia) pullulans were studied. The organism grew well on an acid hydrolysate of ryegrass straw over a wide range of pH and temperature. The optimum temperature and pH for the growth of the organism were 32 degrees C and 5.5, respectively. A cell yield of 1.5 g/liter of straw hydrolysate was obtained. The dried cell mass contained 42.6% crude protein, 0.4% crude fat, and 6.4% nucleic acids. The essential amino acid profile of the microbial protein was comparable to that of Candida utilis. A rat feeding study indicated that the A. pullulans cells were not toxic and that the feed intake, weight gain, and protein efficiency ratio values were superior to those obtained with C. utilis. Once the question of mathogenicity is resolved, A. pullulans could be useful for production of single-cell protein from cellulosic wastes."}
{"id": "PMID:12722", "title": "[Effect of neonatal injections of estradiol, testosterone and cryproterone acetate on plasma and testicular testosterone and on the genital system in adult male mice].", "content": "On day old male mice received a single injection of oestradiol benzoate, testosterone propionate or cyproterone acetate in order to study their action on testicular development, particularly testosterone secretion. Oestrogenization of newborn males leads, when the animals mature, to a high proportion or cryptorchidism, to atrophy of testes and seminal vesicles, and inhibition of spermatogenesis. Testosterone levels were reduced in the plasma. Testosterone propionate produced moderate reduction of testicular weight but spermatogenesis was not impaired. Plasma testosterone level was reduced. Cyproterone acetate increased significantly testicular testosterone level.", "contents": "[Effect of neonatal injections of estradiol, testosterone and cryproterone acetate on plasma and testicular testosterone and on the genital system in adult male mice]. On day old male mice received a single injection of oestradiol benzoate, testosterone propionate or cyproterone acetate in order to study their action on testicular development, particularly testosterone secretion. Oestrogenization of newborn males leads, when the animals mature, to a high proportion or cryptorchidism, to atrophy of testes and seminal vesicles, and inhibition of spermatogenesis. Testosterone levels were reduced in the plasma. Testosterone propionate produced moderate reduction of testicular weight but spermatogenesis was not impaired. Plasma testosterone level was reduced. Cyproterone acetate increased significantly testicular testosterone level."}
{"id": "PMID:12725", "title": "[Problems posed by anesthesia in the hypertensive treated with beta-blockaders].", "content": "The use of beta-blocking agents against hypertension and their rapid extension in daily practice we have to consider the problem of anesthesia of a patient undergoing such treatment. Continuation of the treatment increases the operative risk, discontinuation long before the operation leaves the hypertension to reappear and discontinuation 48 hours before may lead to a coronary or arrhythmic accident. Therefore, except in case of emergency, treatment may be maintained until the day before the operation, and in case or emergency extensive atropinisation is desirable. Finally prescription of selective beta-blocking agents decreases the risks.", "contents": "[Problems posed by anesthesia in the hypertensive treated with beta-blockaders]. The use of beta-blocking agents against hypertension and their rapid extension in daily practice we have to consider the problem of anesthesia of a patient undergoing such treatment. Continuation of the treatment increases the operative risk, discontinuation long before the operation leaves the hypertension to reappear and discontinuation 48 hours before may lead to a coronary or arrhythmic accident. Therefore, except in case of emergency, treatment may be maintained until the day before the operation, and in case or emergency extensive atropinisation is desirable. Finally prescription of selective beta-blocking agents decreases the risks."}
{"id": "PMID:12729", "title": "[The effect of various pH values on in vitro peptic digestion of proteins in the presence of Cu2 ions].", "content": "Studies were carried out to investigate the effect of different pH values on the peptic digestion of soya protein in the presence and in the absence of Cu2+ ions. The studies were performed in vitro at a pH of 2.2 and 3.2, with 2.96 X 10(-5) mole of Cu2+ ions present in 11 of the reaction mixture. The reaction was carried out in a digestion apparatus permitting dialysis of the cleavage products. Different parameters were used as criteria of digestion, viz. the quantity of N contained in the reaction vessel (residue) and in the resulting dialysis products as determined by Kjehldahl microanalysis and automatic amino acid analysis, the proportions of digestion products found in the different molecular ranges after partition of Sephadex G 75 and the composition of amino acids in the cleavage products. From the distribution of the reaction products on the residue and dialysis products and on the different molecular ranges it was found that additions of Cu2+ ions at pH 2.2 produced a considerable inhibition of digestion. With a rise in pH to 3.2 peptic digestion decreased even without the addition of Cu2+. Supplementation of Cu2+ ions produced only a slight additional effect in the molecular range termed \"exclusion limit\". In the case of the amino acids tyrosine and phenylalanine it was found that an increase in pH changed the composition of peptides within the different molecular ranges. Additions of Cu2+ had no influence on the amino acid composition.", "contents": "[The effect of various pH values on in vitro peptic digestion of proteins in the presence of Cu2 ions]. Studies were carried out to investigate the effect of different pH values on the peptic digestion of soya protein in the presence and in the absence of Cu2+ ions. The studies were performed in vitro at a pH of 2.2 and 3.2, with 2.96 X 10(-5) mole of Cu2+ ions present in 11 of the reaction mixture. The reaction was carried out in a digestion apparatus permitting dialysis of the cleavage products. Different parameters were used as criteria of digestion, viz. the quantity of N contained in the reaction vessel (residue) and in the resulting dialysis products as determined by Kjehldahl microanalysis and automatic amino acid analysis, the proportions of digestion products found in the different molecular ranges after partition of Sephadex G 75 and the composition of amino acids in the cleavage products. From the distribution of the reaction products on the residue and dialysis products and on the different molecular ranges it was found that additions of Cu2+ ions at pH 2.2 produced a considerable inhibition of digestion. With a rise in pH to 3.2 peptic digestion decreased even without the addition of Cu2+. Supplementation of Cu2+ ions produced only a slight additional effect in the molecular range termed \"exclusion limit\". In the case of the amino acids tyrosine and phenylalanine it was found that an increase in pH changed the composition of peptides within the different molecular ranges. Additions of Cu2+ had no influence on the amino acid composition."}
{"id": "PMID:12731", "title": "Aging and extrapyramidal function.", "content": "Measurements on human brain samples of some enzymes concerned with neurotransmitter synthesis suggest serious losses with age. The most severe loss found was that in striatal tyrosine hydroxylase activity, the rate-controlling enzyme in the synthesis of dopamine. Cell counts in the substantia nigra where this dopaminergic tract originates suggest that the decrease in enzyme activity is partly due to cell loss, but must largely reflect decreased activity of residual cells. It is possible that this loss may account for some of the difficulties in movement seen in aged individuals and that it might be less if pigment formation in these cells could be inhibited.", "contents": "Aging and extrapyramidal function. Measurements on human brain samples of some enzymes concerned with neurotransmitter synthesis suggest serious losses with age. The most severe loss found was that in striatal tyrosine hydroxylase activity, the rate-controlling enzyme in the synthesis of dopamine. Cell counts in the substantia nigra where this dopaminergic tract originates suggest that the decrease in enzyme activity is partly due to cell loss, but must largely reflect decreased activity of residual cells. It is possible that this loss may account for some of the difficulties in movement seen in aged individuals and that it might be less if pigment formation in these cells could be inhibited."}
{"id": "PMID:12732", "title": "Mannosidosis. New clinical presentation, enzyme studied, and carbohydrate analysis.", "content": "Mannosidosis is a rare inborn error of metabolism characterized by deficiency of the lysosomal enzyme alpha-mannosidase and widespread storage of complex carbohydrate, which is enriched in mannose. Two affected unrelated males, aged 6 and 26 years, are reported. Both had a nonprogressive encephalopathy with moderately severe mental retardation. The older patient showed several unique features, including massive gingival hyperplasia associated with histiocytes containing large amounts of a material with the staining characteristics of glycoprotein. The best determinant of mannose storage proved to be the ratio of mannose to other carbohydrates in urinary polysaccharides. The enzyme deficiency in this disease is most convincingly demonstrated at pH values below 4.0. The ability of zinc to activate the mutant enzyme in vitro offers a possible mode of therapy for this disease. Retarded individuals with a Hurler-like appearance and gum hyperplasia of unknown cause should be screened for alpha-mannosidase deficiency.", "contents": "Mannosidosis. New clinical presentation, enzyme studied, and carbohydrate analysis. Mannosidosis is a rare inborn error of metabolism characterized by deficiency of the lysosomal enzyme alpha-mannosidase and widespread storage of complex carbohydrate, which is enriched in mannose. Two affected unrelated males, aged 6 and 26 years, are reported. Both had a nonprogressive encephalopathy with moderately severe mental retardation. The older patient showed several unique features, including massive gingival hyperplasia associated with histiocytes containing large amounts of a material with the staining characteristics of glycoprotein. The best determinant of mannose storage proved to be the ratio of mannose to other carbohydrates in urinary polysaccharides. The enzyme deficiency in this disease is most convincingly demonstrated at pH values below 4.0. The ability of zinc to activate the mutant enzyme in vitro offers a possible mode of therapy for this disease. Retarded individuals with a Hurler-like appearance and gum hyperplasia of unknown cause should be screened for alpha-mannosidase deficiency."}
{"id": "PMID:12733", "title": "[The measurement of the partial pressure of oxygen and carbon dioxide and pH of the aqueous humor in man. A preliminary study on 32 normal eyes].", "content": "Using a micromethod the authors have measured the pH, and the partial pressure of oxygen and carbon dioxide in the aqueous humour. The results are presented in 32 normal eyes. The authors have studied the variation of these levels in the aqueous in comparison with the same levels measured at the same time under the same conditions in the arterial blood.", "contents": "[The measurement of the partial pressure of oxygen and carbon dioxide and pH of the aqueous humor in man. A preliminary study on 32 normal eyes]. Using a micromethod the authors have measured the pH, and the partial pressure of oxygen and carbon dioxide in the aqueous humour. The results are presented in 32 normal eyes. The authors have studied the variation of these levels in the aqueous in comparison with the same levels measured at the same time under the same conditions in the arterial blood."}
{"id": "PMID:12739", "title": "Electrophoretic demonstration and inital characterization of human red cell NAD(P)+ase.", "content": "A method for electrophoretic detection of NAD(P)+ase solubilized from red cell membranes is described. The method reveals both NAD+ase and NADP+ase and can be applied to a screening procedure for the detection of electrophoretic variants. The initial chracterization of the solubilized enzyme is also described.", "contents": "Electrophoretic demonstration and inital characterization of human red cell NAD(P)+ase. A method for electrophoretic detection of NAD(P)+ase solubilized from red cell membranes is described. The method reveals both NAD+ase and NADP+ase and can be applied to a screening procedure for the detection of electrophoretic variants. The initial chracterization of the solubilized enzyme is also described."}
{"id": "PMID:12740", "title": "The reactions of D-glyceraldehyde 3-phosphate with thiols and the holoenzyme of D-glyceraldehyde 3-phosphate dehydrogenase and of inorganic phosphate with the acyl-holoenzyme.", "content": "D-Glyceraldehyde 3-phosphate forms adducts with thiols. These adducts, which are presumed to be hemithioacetals, equilibrate rapidly with the unhydrated form of the aldehyde, which is the subtrate for D-glyceraldehyde 3-phosphate dehydrogenase. The adduct provides a substrate buffer system whereby a constant low free aldehyde concentration can be maintained during the oxidation of aldehyde by the enzyme and NAD+. With this system, the kinetics of the association of the aldehyde with the enzyme were examined. The rate profile for this reaction is a single exponential process, showing that all four active sites of the enzyme have equivalent and independent reactivity towards the aldehyde, with an apparent second-order rate constant of 5 X 10(7)M-1-S-1 at pH8.0 and 21 degrees C. The second-order rate constant becomes 8 X 10(7)M-1-S-1 when account is taken of the forward and reverse catalytic rate constants of the dehydrogenase. The pH-dependence of the observed rate constant is consistent with a requirement for the unprotonated form of a group of pK 6.1, which is the pK observed for second ionization of glyceraldehyde 3-phosphate. The rate of phosphorolysis of the acyl-enzyme intermediate during the steady-state oxidative phosphorylation of the aldehyde was studied, and is proportional to the total Pi concentration up to at least 1 mM-Pi at pH 7.5. The pH-dependence of the rate of NADH generation under these conditions can be explained by the rate law d[NADA]/dt = k[acy] holoenzyme][PO4(3-)-A1, where thioester bond, although kinetically indistinguishable rate equations for the reaction are possible. The rates of the phosphorolysis reaction and of the aldehyde-association reaction decrease with increasing ionic strength, suggesting that the active site of the enzyme has cationic groups which are involved in the reaction of the enzyme with anionic substrates.", "contents": "The reactions of D-glyceraldehyde 3-phosphate with thiols and the holoenzyme of D-glyceraldehyde 3-phosphate dehydrogenase and of inorganic phosphate with the acyl-holoenzyme. D-Glyceraldehyde 3-phosphate forms adducts with thiols. These adducts, which are presumed to be hemithioacetals, equilibrate rapidly with the unhydrated form of the aldehyde, which is the subtrate for D-glyceraldehyde 3-phosphate dehydrogenase. The adduct provides a substrate buffer system whereby a constant low free aldehyde concentration can be maintained during the oxidation of aldehyde by the enzyme and NAD+. With this system, the kinetics of the association of the aldehyde with the enzyme were examined. The rate profile for this reaction is a single exponential process, showing that all four active sites of the enzyme have equivalent and independent reactivity towards the aldehyde, with an apparent second-order rate constant of 5 X 10(7)M-1-S-1 at pH8.0 and 21 degrees C. The second-order rate constant becomes 8 X 10(7)M-1-S-1 when account is taken of the forward and reverse catalytic rate constants of the dehydrogenase. The pH-dependence of the observed rate constant is consistent with a requirement for the unprotonated form of a group of pK 6.1, which is the pK observed for second ionization of glyceraldehyde 3-phosphate. The rate of phosphorolysis of the acyl-enzyme intermediate during the steady-state oxidative phosphorylation of the aldehyde was studied, and is proportional to the total Pi concentration up to at least 1 mM-Pi at pH 7.5. The pH-dependence of the rate of NADH generation under these conditions can be explained by the rate law d[NADA]/dt = k[acy] holoenzyme][PO4(3-)-A1, where thioester bond, although kinetically indistinguishable rate equations for the reaction are possible. The rates of the phosphorolysis reaction and of the aldehyde-association reaction decrease with increasing ionic strength, suggesting that the active site of the enzyme has cationic groups which are involved in the reaction of the enzyme with anionic substrates."}
{"id": "PMID:12741", "title": "A model for the kinetics of activation and catalysis of ribulose 1,5-bisphosphate carboxylase.", "content": "Further evidence for time-dependent interconversions between active and inactive states of ribulose 1,5-bisphosphate carboxylase is presented. It was found that ribulose bisphosphate oxygenase and ribulose bisphosphate carboxylase could be totally inactivated by excluding CO2 and Mg2+ during dialysis of the enzyme at 4 degrees C. When initially inactive enzyme was assayed, the rate of reaction continually increased with time, and the rate was inversely related to the ribulose bisphosphare concentration. The initial rate of fully activated enzyme showed normal Michaelis-Menten kinetics with respect to ribulose bisphosphate (Km = 10muM). Activation was shown to depend on both CO2 and Mg2+ concentrations, with equilibrium constants for activation of about 100muM and 1 mM respectively. In contrast with activation, catalysis appeared to be independent of Mg2+ concentration, but dependent on CO2 concentration, with a Km(CO2) of about 10muM. By studying activation and de-activation of ribulose bisphosphate carboxylase as a function of CO2 and Mg2+ concentrations, the values of the kinetic constants for these actions have been determined. We propose a model for activation and catalysis of ribulose bisphosphate carboxylase: (see book) where E represents free inactive enzyme; complex in parentheses, activated enzyme; R, ribulose bisphosphate; M, Mg2+; C, CO2; P, the product. We propose that ribulose bisphosphate can bind to both the active and inactive forms of the enzyme, and slow inter-conversion between the two states occurs.", "contents": "A model for the kinetics of activation and catalysis of ribulose 1,5-bisphosphate carboxylase. Further evidence for time-dependent interconversions between active and inactive states of ribulose 1,5-bisphosphate carboxylase is presented. It was found that ribulose bisphosphate oxygenase and ribulose bisphosphate carboxylase could be totally inactivated by excluding CO2 and Mg2+ during dialysis of the enzyme at 4 degrees C. When initially inactive enzyme was assayed, the rate of reaction continually increased with time, and the rate was inversely related to the ribulose bisphosphare concentration. The initial rate of fully activated enzyme showed normal Michaelis-Menten kinetics with respect to ribulose bisphosphate (Km = 10muM). Activation was shown to depend on both CO2 and Mg2+ concentrations, with equilibrium constants for activation of about 100muM and 1 mM respectively. In contrast with activation, catalysis appeared to be independent of Mg2+ concentration, but dependent on CO2 concentration, with a Km(CO2) of about 10muM. By studying activation and de-activation of ribulose bisphosphate carboxylase as a function of CO2 and Mg2+ concentrations, the values of the kinetic constants for these actions have been determined. We propose a model for activation and catalysis of ribulose bisphosphate carboxylase: (see book) where E represents free inactive enzyme; complex in parentheses, activated enzyme; R, ribulose bisphosphate; M, Mg2+; C, CO2; P, the product. We propose that ribulose bisphosphate can bind to both the active and inactive forms of the enzyme, and slow inter-conversion between the two states occurs."}
{"id": "PMID:12742", "title": "Identity of isoenzyme 1 of histidine-pyruvate aminotransferase with serine-pyruvate aminotransferase.", "content": "After glucagon injection, rats showed virtually identical percentage increases in hepatic histidine-pyruvate aminotransferase and serine-pyruvate aminotransferase activities, both in the mitochondria and in the cytosol. Histidine-pyruvate aminotransferase isoenzyme 1, with pI8.0, was purified to homogeneity from the mitochondrial fraction of liver from glucagon-injected rats. The purified enzyme catalysed transamination between a number of amino acids and pyruvate or phenylpyruvate. For transamination with pyruvate, the activity with serine reached a constant ratio to that with histidine during purification, which was unchanged by a variety of treatments of the purified enzyme. Serine was found to act as a competitive inhibitor of histidine transamination, and histidine of serine transamination. These results suggest that histidine-pyruvate amino-transferase isoenzymes 1 is identical with serine-pyruvate aminotransferase. The enzyme is probably composed of two identical subunits with mol. wt. approx. 38000. The absorbance maximum at 410 nm and the inhibition by carbonyl reagents strongly indicate the presence of pyridoxal phosphate.", "contents": "Identity of isoenzyme 1 of histidine-pyruvate aminotransferase with serine-pyruvate aminotransferase. After glucagon injection, rats showed virtually identical percentage increases in hepatic histidine-pyruvate aminotransferase and serine-pyruvate aminotransferase activities, both in the mitochondria and in the cytosol. Histidine-pyruvate aminotransferase isoenzyme 1, with pI8.0, was purified to homogeneity from the mitochondrial fraction of liver from glucagon-injected rats. The purified enzyme catalysed transamination between a number of amino acids and pyruvate or phenylpyruvate. For transamination with pyruvate, the activity with serine reached a constant ratio to that with histidine during purification, which was unchanged by a variety of treatments of the purified enzyme. Serine was found to act as a competitive inhibitor of histidine transamination, and histidine of serine transamination. These results suggest that histidine-pyruvate amino-transferase isoenzymes 1 is identical with serine-pyruvate aminotransferase. The enzyme is probably composed of two identical subunits with mol. wt. approx. 38000. The absorbance maximum at 410 nm and the inhibition by carbonyl reagents strongly indicate the presence of pyridoxal phosphate."}
{"id": "PMID:12743", "title": "Modification of glyceraldehyde 3-phosphate dehydrogenase activity by adsorption on phospholipid vesicles.", "content": "1. The adsorption of [14C]carboxymethylated glyceraldehyde 3-phosphate dehydrogenase to negatively charged liposomes of phsphatidic acid/phosphatidylcholine (3:7, w/w) was investigated. The apparent association constant at I/2 = 60, pH 7.6, was 0.4 X 10(6)M-1. Adsorption decreased as ionic strength and pH were increased. 2. In the presence of negatively charged liposomes, the Km value for glyceraldehyde 3-phosphate of glyceraldehyde 3-phosphate dehydrogenase was increased and Vmax. decreased. In the presence of positively charged liposomes, the Km value for glyceraldehyde 3-phosphate decreased and there was no significant change in Vmax. Addition of Triton X-100 abolished the effect of both positively and negatively charged liposomes on the kinetic properties of the enzyme.", "contents": "Modification of glyceraldehyde 3-phosphate dehydrogenase activity by adsorption on phospholipid vesicles. 1. The adsorption of [14C]carboxymethylated glyceraldehyde 3-phosphate dehydrogenase to negatively charged liposomes of phsphatidic acid/phosphatidylcholine (3:7, w/w) was investigated. The apparent association constant at I/2 = 60, pH 7.6, was 0.4 X 10(6)M-1. Adsorption decreased as ionic strength and pH were increased. 2. In the presence of negatively charged liposomes, the Km value for glyceraldehyde 3-phosphate of glyceraldehyde 3-phosphate dehydrogenase was increased and Vmax. decreased. In the presence of positively charged liposomes, the Km value for glyceraldehyde 3-phosphate decreased and there was no significant change in Vmax. Addition of Triton X-100 abolished the effect of both positively and negatively charged liposomes on the kinetic properties of the enzyme."}
{"id": "PMID:12744", "title": "The transport and oxidation of succinate by Ehrlich ascites-tumour cells.", "content": "The transport and oxidation of succinate by functionally intact Ehrlich ascites-tumour cells was investigated. On the basis of pH dependence and inhibitor sensitivity it was concluded that succinate may be transported across the cell membrane by the organic anion carrier system. Thus the ability of isolated Ehrlich cells to oxidize succinate is real, and is not necessarily a result of damage to cell integrity.", "contents": "The transport and oxidation of succinate by Ehrlich ascites-tumour cells. The transport and oxidation of succinate by functionally intact Ehrlich ascites-tumour cells was investigated. On the basis of pH dependence and inhibitor sensitivity it was concluded that succinate may be transported across the cell membrane by the organic anion carrier system. Thus the ability of isolated Ehrlich cells to oxidize succinate is real, and is not necessarily a result of damage to cell integrity."}
{"id": "PMID:12745", "title": "The role of glucocorticoids in the regulation of the diurnal rhythm of hepatic beta-hydroxy-beta-methylglutaryl-coenzyme A reductase and cholesterol 7 alpha-hydroxylase.", "content": "The microsomal activities of the hepatic enzymes hydroxymethylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase exhibit a diurnal rhythm with maximum activities observed during the dark period and minimum activities around noon (12:00h). This diurnal rhythm was maintained for both enzymes after adrenalectomy, but the amplitude of variation for the activity of both enzymes was greatly decreased. A single injection of cortisol administered to adrenalectomized rats 3h before the expected maximum in enzyme activity resulted in a twofold increase in the activity of both enzymes 3h later, at values similar to those observed for control rats killed at the same time. This response appeared to require protein synthesis, since it was blocked by actinomycin D. However, the administration of cortisol to adrenalectomized rats 3 h before the expected minimum did not result in significant change in the activity of hydroxymethylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase 3 h later. Kinetic studies of cholic acid metabolism in vivo demonstrated that adrenalectomy results in a significant decrease in the rate of synthesis of cholic acid and a considerable decrease in the pool size of cholic acid and its metabolic products. Treatment of adrenalectomized rats with cortisol increased the rate oonsistent with the effects of adrenalectomy and cortisol treatment on the activity of cholesterol 7alpha-hydroxylase.", "contents": "The role of glucocorticoids in the regulation of the diurnal rhythm of hepatic beta-hydroxy-beta-methylglutaryl-coenzyme A reductase and cholesterol 7 alpha-hydroxylase. The microsomal activities of the hepatic enzymes hydroxymethylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase exhibit a diurnal rhythm with maximum activities observed during the dark period and minimum activities around noon (12:00h). This diurnal rhythm was maintained for both enzymes after adrenalectomy, but the amplitude of variation for the activity of both enzymes was greatly decreased. A single injection of cortisol administered to adrenalectomized rats 3h before the expected maximum in enzyme activity resulted in a twofold increase in the activity of both enzymes 3h later, at values similar to those observed for control rats killed at the same time. This response appeared to require protein synthesis, since it was blocked by actinomycin D. However, the administration of cortisol to adrenalectomized rats 3 h before the expected minimum did not result in significant change in the activity of hydroxymethylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase 3 h later. Kinetic studies of cholic acid metabolism in vivo demonstrated that adrenalectomy results in a significant decrease in the rate of synthesis of cholic acid and a considerable decrease in the pool size of cholic acid and its metabolic products. Treatment of adrenalectomized rats with cortisol increased the rate oonsistent with the effects of adrenalectomy and cortisol treatment on the activity of cholesterol 7alpha-hydroxylase."}
{"id": "PMID:12746", "title": "Mechanism of inhibition by carbonyl cyanide m-chlorophenylhydrazone and sodium deoxycholate of cytochrome P-450-catalysed hepatic microsomal drug metabolism.", "content": "1. Treatment of liver microsomal fraction with 0.03-0.12% sodium deoxycholate and 0.005-0.06 mM carbonyl cyanide m-chlorophenylhydrazone decreases phospholipid-dependent hydrophobicity of the microsomal membrane, assayed by the kinetics of 8-anilinonaphthalene-1-sulphonate binding and ethyl isocyanide difference spectra. 2. Sodium deoxycholate at a concentration of 0.01% lacks its detergent properties, but competitively inhibits aminopyrine binding and activates the initial rate of NADPH-cytochrome P-450 reductase. In the presence of 0.03-0.09% sodium deoxycholate the rate-limiting factor in p-hydroxylation of aniline is the content of cytochrome P-450. and that for N-demethylation of aminopyrine is the activity of NADPH-cytochrome P-450 reductase. 3. Carbonyl cyanide m-chlorophenylhydrazone has no effect on the binding and metabolism of aniline; investigation of its inhibiting effect on aminopyrine N-demethylase established that the rate-limiting reaction is the dissociation of the enzyme-substrate complex in the microsomal preparations. 4. In the mechanism of action of carbonyl cyanide m-chlorophenylhydrazone the key step may be the electrostatic interaction of its protonated form and one of the forms of activated oxygen at the catalytic centre of cytochrome P-450. 5. at least two different phospholipid-dependent hydrophobic zones are assumed to exist in the microsomal membrane, both coupled with cytochrome P-450. One of them reveals selective sensitivity to the protonation action of carbonyl cyanide m-chlorophenylhydrazone and contains the 'binding protein' for type I substrates and NADPH-cytochrome P-450 reductase; the other contains the cytochrome P-450 haem group and binding sites for type II substrates.", "contents": "Mechanism of inhibition by carbonyl cyanide m-chlorophenylhydrazone and sodium deoxycholate of cytochrome P-450-catalysed hepatic microsomal drug metabolism. 1. Treatment of liver microsomal fraction with 0.03-0.12% sodium deoxycholate and 0.005-0.06 mM carbonyl cyanide m-chlorophenylhydrazone decreases phospholipid-dependent hydrophobicity of the microsomal membrane, assayed by the kinetics of 8-anilinonaphthalene-1-sulphonate binding and ethyl isocyanide difference spectra. 2. Sodium deoxycholate at a concentration of 0.01% lacks its detergent properties, but competitively inhibits aminopyrine binding and activates the initial rate of NADPH-cytochrome P-450 reductase. In the presence of 0.03-0.09% sodium deoxycholate the rate-limiting factor in p-hydroxylation of aniline is the content of cytochrome P-450. and that for N-demethylation of aminopyrine is the activity of NADPH-cytochrome P-450 reductase. 3. Carbonyl cyanide m-chlorophenylhydrazone has no effect on the binding and metabolism of aniline; investigation of its inhibiting effect on aminopyrine N-demethylase established that the rate-limiting reaction is the dissociation of the enzyme-substrate complex in the microsomal preparations. 4. In the mechanism of action of carbonyl cyanide m-chlorophenylhydrazone the key step may be the electrostatic interaction of its protonated form and one of the forms of activated oxygen at the catalytic centre of cytochrome P-450. 5. at least two different phospholipid-dependent hydrophobic zones are assumed to exist in the microsomal membrane, both coupled with cytochrome P-450. One of them reveals selective sensitivity to the protonation action of carbonyl cyanide m-chlorophenylhydrazone and contains the 'binding protein' for type I substrates and NADPH-cytochrome P-450 reductase; the other contains the cytochrome P-450 haem group and binding sites for type II substrates."}
{"id": "PMID:12747", "title": "Phosphatidylinositol kinase and diphosphoinositide kinase of rat kidney cortex: properties and subcellular localization.", "content": "The properties of phosphatidylinositol kinase and diphosphoinositide kinase from rat kidney cortex were studied. The enzymes were completely Mg2+-dependent. Cutscum detergent activated phosphatidylinositol kinase, but diphosphoinositide kinase was inhibited by all detergents tested. The pH optima were 7.7 for phosphatidylinositol kinase and 6.5 for diphosphoinositide kinase. On subcellular fractionation of kidney-cortex homogenates by differential centriflgation, the distribution of phosphatidylinositol kinase resembled that of the marker enzymes for brush-border, endoplasmic-reticulum and Golgi membranes. Diphosphoinositide kinase distribution resembled that of thiamin pyrophosphatase (assayed in the absence of ATP), diphosphoinositide phosphatase and triphosphoinositide phosphatase. Activities of both kinases were low in purified brush-border fragments. Diphosphoinositide kinase is probably localized in the Golgi complex.", "contents": "Phosphatidylinositol kinase and diphosphoinositide kinase of rat kidney cortex: properties and subcellular localization. The properties of phosphatidylinositol kinase and diphosphoinositide kinase from rat kidney cortex were studied. The enzymes were completely Mg2+-dependent. Cutscum detergent activated phosphatidylinositol kinase, but diphosphoinositide kinase was inhibited by all detergents tested. The pH optima were 7.7 for phosphatidylinositol kinase and 6.5 for diphosphoinositide kinase. On subcellular fractionation of kidney-cortex homogenates by differential centriflgation, the distribution of phosphatidylinositol kinase resembled that of the marker enzymes for brush-border, endoplasmic-reticulum and Golgi membranes. Diphosphoinositide kinase distribution resembled that of thiamin pyrophosphatase (assayed in the absence of ATP), diphosphoinositide phosphatase and triphosphoinositide phosphatase. Activities of both kinases were low in purified brush-border fragments. Diphosphoinositide kinase is probably localized in the Golgi complex."}
{"id": "PMID:12748", "title": "Physicochemical characteristics of the glycosaminoglycan-lysosomal enzyme interaction in vitro. A model of control of leucocytic lysosomal activity.", "content": "1. The activities of 30 different lysosomal enzymes were determined in vitro in the presence of the sulphated glycosaminoglycans, heparin and chondroitin sulphate, all the enzymes being measured on a density-gradient-purified lysosomal fraction. 2. Each enzyme was studied as a function of the pH of the incubation medium. In general the presence of sulphated glycosaminoglycans induced a strong pH-dependent inhibition of lysosomal enzymes at pH values lower than 5.0, with full activity at higher pH values. However, in the particular case of lysozyme and phospholipase A2 the heparin-induced inhibition was maintained in the pH range 4.0-7.0. 3. For certain enzymes, such as acid beta-glycerophosphatase, alpha-galactosidase, acid lipase, lysozyme and phospholipase A2, the pH-dependent behaviour obtained in the presence of heparin was quite different to that obtained with chondroitin sulphate, suggesting the existence of physicochemical characteristic factors playing a role in the intermolecular interaction for each of the sulphated glycosaminoglycans studied. 4. Except in the particular case of peroxidase activity, in all other lysosomal enzymes measured the glycosaminoglycan-enzyme complex formation was a temperature-and time-independent phenomenon. 5. The effects of the ionic strength and pH on this intermolecular interaction reinforce the concept of an electrostatic reversible interaction between anionic groups of the glycosaminoglycans and cationic groups on the enzyme molecule. 6. As leucocytic primary lysosomes have a very acid intragranular pH and large amounts of chondroitin sulphate, we propose that this glycosaminoglycan might act as molecular regulator of leucocytic activity, by inhibiting lysosomal enzymes when the intragranular pH is below the pI of lysosomal enzymes. This fact, plus the intravacuolar pH changes described during the phagocytic process, might explain the unresponsiveness of lysosomal enzymes against each other existing in primary lysosomes as well as its full activation at pH values occurring in secondary lysosomes during the phagocytic process.", "contents": "Physicochemical characteristics of the glycosaminoglycan-lysosomal enzyme interaction in vitro. A model of control of leucocytic lysosomal activity. 1. The activities of 30 different lysosomal enzymes were determined in vitro in the presence of the sulphated glycosaminoglycans, heparin and chondroitin sulphate, all the enzymes being measured on a density-gradient-purified lysosomal fraction. 2. Each enzyme was studied as a function of the pH of the incubation medium. In general the presence of sulphated glycosaminoglycans induced a strong pH-dependent inhibition of lysosomal enzymes at pH values lower than 5.0, with full activity at higher pH values. However, in the particular case of lysozyme and phospholipase A2 the heparin-induced inhibition was maintained in the pH range 4.0-7.0. 3. For certain enzymes, such as acid beta-glycerophosphatase, alpha-galactosidase, acid lipase, lysozyme and phospholipase A2, the pH-dependent behaviour obtained in the presence of heparin was quite different to that obtained with chondroitin sulphate, suggesting the existence of physicochemical characteristic factors playing a role in the intermolecular interaction for each of the sulphated glycosaminoglycans studied. 4. Except in the particular case of peroxidase activity, in all other lysosomal enzymes measured the glycosaminoglycan-enzyme complex formation was a temperature-and time-independent phenomenon. 5. The effects of the ionic strength and pH on this intermolecular interaction reinforce the concept of an electrostatic reversible interaction between anionic groups of the glycosaminoglycans and cationic groups on the enzyme molecule. 6. As leucocytic primary lysosomes have a very acid intragranular pH and large amounts of chondroitin sulphate, we propose that this glycosaminoglycan might act as molecular regulator of leucocytic activity, by inhibiting lysosomal enzymes when the intragranular pH is below the pI of lysosomal enzymes. This fact, plus the intravacuolar pH changes described during the phagocytic process, might explain the unresponsiveness of lysosomal enzymes against each other existing in primary lysosomes as well as its full activation at pH values occurring in secondary lysosomes during the phagocytic process."}
{"id": "PMID:12749", "title": "Further investigation of the biosynthesis of caffeine in tea plants (Camellia sinensis L.). Methylation of transfer ribonucleic acid by tea leaf extracts.", "content": "1. The tRNA methyltransferase activity in vitro of leaves, cotyledons and roots of 85-day-old tea seedlings was studied. 2. The activity of extracts prepared from tea leaves with Polycar AT (insoluble polyvinylpyrrolidine) had optimum pH7.7 and was greatly influenced by thiol compounds, but only slightly by metal ions and ammonium acetate. 3. The activities of extracts, expressed per mg of protein, were as follows: roots greater than leaves greater than cotyledons. The only methylated base isolated after incubation with these preparations was 1-methyladenine. 4. The results did not support the view of involvement of methylation of nucleic acids in caffeine biosynthesis in tea plants. In contrast, it is suggested that theophylline is synthesized from the specific methylated precursor in nucleic acids, namely 1-methyladenylic acid, via 1-methylxanthine.", "contents": "Further investigation of the biosynthesis of caffeine in tea plants (Camellia sinensis L.). Methylation of transfer ribonucleic acid by tea leaf extracts. 1. The tRNA methyltransferase activity in vitro of leaves, cotyledons and roots of 85-day-old tea seedlings was studied. 2. The activity of extracts prepared from tea leaves with Polycar AT (insoluble polyvinylpyrrolidine) had optimum pH7.7 and was greatly influenced by thiol compounds, but only slightly by metal ions and ammonium acetate. 3. The activities of extracts, expressed per mg of protein, were as follows: roots greater than leaves greater than cotyledons. The only methylated base isolated after incubation with these preparations was 1-methyladenine. 4. The results did not support the view of involvement of methylation of nucleic acids in caffeine biosynthesis in tea plants. In contrast, it is suggested that theophylline is synthesized from the specific methylated precursor in nucleic acids, namely 1-methyladenylic acid, via 1-methylxanthine."}
{"id": "PMID:12750", "title": "Effect of phenylalanine metabolites on the activities of enzymes of ketone-body utilization in brain of suckling rats.", "content": "1. The effects of phenylalanine and its metabolites (phenylacetate, phenethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) 3-oxo acid CoA-transferase (EC 2.8.3.5) and acetoacetyl-CoA thiolase (EC 2.3.1.9) in brain of suckling rats were investigated. 2. The 3-hydroxybutyrate dehydrogenase from the brain of suckling rats had a Km for 3-hydroxybutyrate of 1.2 mM. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the enzyme activity with Ki values of 0.5, 1.3 and 4.7 mM respectively. 3. The suckling-rat brain 3-oxo acid CoA-transferase activity had a Km for acetoacetate of 0.665 mM and for succinyl (3-carboxypropionyl)-CoA of 0.038 mM. The enzyme was inhibited with respect to acetoacetate by phenylpyruvate (Ki equals 1.3 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). The reaction in the direction of acetoacetate was also inhibited by phenylpyruvate (Ki equals 1.6 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). 4. Phenylpyruvate inhibited with respect to acetoacetyl-CoA both the mitochondrial (Ki equals 3.2 mM) and cytoplasmic (Ki equals 5.2 mM) acetoacetyl-CoA thiolase activities. 5. The results suggest that inhibition of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities may impair ketone-body utilization and hence lipid synthesis in the developing brain. This suggestion is discussed with reference to the pathogenesis of mental retardation in phenylketonuria.", "contents": "Effect of phenylalanine metabolites on the activities of enzymes of ketone-body utilization in brain of suckling rats. 1. The effects of phenylalanine and its metabolites (phenylacetate, phenethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) 3-oxo acid CoA-transferase (EC 2.8.3.5) and acetoacetyl-CoA thiolase (EC 2.3.1.9) in brain of suckling rats were investigated. 2. The 3-hydroxybutyrate dehydrogenase from the brain of suckling rats had a Km for 3-hydroxybutyrate of 1.2 mM. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the enzyme activity with Ki values of 0.5, 1.3 and 4.7 mM respectively. 3. The suckling-rat brain 3-oxo acid CoA-transferase activity had a Km for acetoacetate of 0.665 mM and for succinyl (3-carboxypropionyl)-CoA of 0.038 mM. The enzyme was inhibited with respect to acetoacetate by phenylpyruvate (Ki equals 1.3 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). The reaction in the direction of acetoacetate was also inhibited by phenylpyruvate (Ki equals 1.6 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). 4. Phenylpyruvate inhibited with respect to acetoacetyl-CoA both the mitochondrial (Ki equals 3.2 mM) and cytoplasmic (Ki equals 5.2 mM) acetoacetyl-CoA thiolase activities. 5. The results suggest that inhibition of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities may impair ketone-body utilization and hence lipid synthesis in the developing brain. This suggestion is discussed with reference to the pathogenesis of mental retardation in phenylketonuria."}
{"id": "PMID:12751", "title": "Nicotinamide-adenine dinucleotide-linked \"malic\" enzyme in flight muscle of the tse-tse fly (Glossina) and other insects.", "content": "1. A high activity of NAD-linked \"malic\" enzyme was found in homogenates of flight muscle of different species of tse-tse fly (Glossina). The activity was the same as, or higher than, that of malate dehydrogenase and more than 20-fold that of NADP-linked \"malic\" enzyme. A similar enzyme was found in the flight muscle of all other insects investigated, but at much lower activities. 2. ACa2+-stimulated oxaloacetate decarboxylase activity was present in all insect flight-muscle preparations investigated, in constant proportion to the NAD-linked \"malic\" enzyme. 3. A partial purification of the NAD-linked \"malic\" enzyme from Glossina was effected by DEAE-cellulose chromatography, which separated the enzyme from malate dehydrogenase and NADP-linked \"malic\" enzyme, but not from oxaloacetate decarboxylase. 4. The intracellular localization of the NAD-linked \"malic\" enzyme was predominantly mitochondrial; latency studies suggested a localization in the mitochondrial matrix space. 5. Studies on the partially purified enzyme demonstrated that it had a pH optimum between 7.6 and 7.9. It required Mg2+ or Mn2+ for activity; Ca2+ was not effective. The maximum rate was the same with either cation, but the concentration of Mn2+ required was 100 times less than that of Mg2+. Acitivity with NADP was only 1-3% of that with NAD, unless very high (greater than 10mM) concentrations of Mn2+ were present. 6. It is suggested that the NAD-linked \"malic\" enzyme functions in the proline-oxidation pathway predominant in tse-tse fly flight muscle.", "contents": "Nicotinamide-adenine dinucleotide-linked \"malic\" enzyme in flight muscle of the tse-tse fly (Glossina) and other insects. 1. A high activity of NAD-linked \"malic\" enzyme was found in homogenates of flight muscle of different species of tse-tse fly (Glossina). The activity was the same as, or higher than, that of malate dehydrogenase and more than 20-fold that of NADP-linked \"malic\" enzyme. A similar enzyme was found in the flight muscle of all other insects investigated, but at much lower activities. 2. ACa2+-stimulated oxaloacetate decarboxylase activity was present in all insect flight-muscle preparations investigated, in constant proportion to the NAD-linked \"malic\" enzyme. 3. A partial purification of the NAD-linked \"malic\" enzyme from Glossina was effected by DEAE-cellulose chromatography, which separated the enzyme from malate dehydrogenase and NADP-linked \"malic\" enzyme, but not from oxaloacetate decarboxylase. 4. The intracellular localization of the NAD-linked \"malic\" enzyme was predominantly mitochondrial; latency studies suggested a localization in the mitochondrial matrix space. 5. Studies on the partially purified enzyme demonstrated that it had a pH optimum between 7.6 and 7.9. It required Mg2+ or Mn2+ for activity; Ca2+ was not effective. The maximum rate was the same with either cation, but the concentration of Mn2+ required was 100 times less than that of Mg2+. Acitivity with NADP was only 1-3% of that with NAD, unless very high (greater than 10mM) concentrations of Mn2+ were present. 6. It is suggested that the NAD-linked \"malic\" enzyme functions in the proline-oxidation pathway predominant in tse-tse fly flight muscle."}
{"id": "PMID:12752", "title": "The electrophoretic properties and aggregation of mouse lymphoma cells, chinese-hamster fibroblasts and a somatic-cell hybrid.", "content": "1. The electrophoretic mobilities of a mouse lymphoma cell, a Chinese-hamster fibroblast and a somatic-cell hybrid (also fibroblastic), produced by fusion of the hamster cell and a mouse lymphoma cell, were measured at 25 degrees C over a range of pH, concentration of Ca2+ ions and concentration of La3+ ions. 2. All the cells have pI at pH3.5. 3. Ca2+ ions decrease the mobilities and zeta potentials of the cells to zero in the range 1-100mM. 4. La3+ ions lower the mobilities and zeta potentials in the range 10 muM-1 mM, and the cells become positively charged above 1 mM. 5. The data are consistent with specific adsorption of La3+ ions on approx. 2 X 10(14) sites/m2 of cell surface with a free energy of approx. -37kJ/mol. 6. The effects of Ca2+, La3+ and ionic strength on the extent of aggregation of the cells and of neuraminidase-treated cells were studied. 7. Ca2+ ions do not markedly increase aggregation, whereas La3+ ions gave rise to extensive aggregation in the range 10 muM-1 mM, corresponding to the region of La3+ adsorption. 8. Both fibroblastic cell lines are aggregated at high ionic strength. 9. The fibroblastic cells have larger amounts of trypsin-sensitive carbohydrate than does the lymphoma cell; the possible role of this material in cellular aggregation is discussed.", "contents": "The electrophoretic properties and aggregation of mouse lymphoma cells, chinese-hamster fibroblasts and a somatic-cell hybrid. 1. The electrophoretic mobilities of a mouse lymphoma cell, a Chinese-hamster fibroblast and a somatic-cell hybrid (also fibroblastic), produced by fusion of the hamster cell and a mouse lymphoma cell, were measured at 25 degrees C over a range of pH, concentration of Ca2+ ions and concentration of La3+ ions. 2. All the cells have pI at pH3.5. 3. Ca2+ ions decrease the mobilities and zeta potentials of the cells to zero in the range 1-100mM. 4. La3+ ions lower the mobilities and zeta potentials in the range 10 muM-1 mM, and the cells become positively charged above 1 mM. 5. The data are consistent with specific adsorption of La3+ ions on approx. 2 X 10(14) sites/m2 of cell surface with a free energy of approx. -37kJ/mol. 6. The effects of Ca2+, La3+ and ionic strength on the extent of aggregation of the cells and of neuraminidase-treated cells were studied. 7. Ca2+ ions do not markedly increase aggregation, whereas La3+ ions gave rise to extensive aggregation in the range 10 muM-1 mM, corresponding to the region of La3+ adsorption. 8. Both fibroblastic cell lines are aggregated at high ionic strength. 9. The fibroblastic cells have larger amounts of trypsin-sensitive carbohydrate than does the lymphoma cell; the possible role of this material in cellular aggregation is discussed."}
{"id": "PMID:12753", "title": "Mitochondrial adenosine triphosphatase of the fission yeast, Schizosaccharomyces pombe 972h-. Changes in activity and inhibitor-sensitivity in response to catabolite repression.", "content": "1. The specific activity of mitochondrial ATPase (adenosine triphosphatase) in extracts of Schizosaccharomyces pombe decreased 2.5-fold as the glucose concentration in the growth medium decreased from 50mM to 15mM. 2. During the late exponential phase of growth, ATPase activity doubled. 3. Sensitivity to oligomycin and Dio-9 as measured by values for I50(mug of inhibitor/mg of protein giving 50% inhibition) at pH 6.8 increased sixfold and ninefold respectively during the initial decrease in ATPase activity, and this degree of sensitivity was maintained for the remainder of the growth cycle. 4. Increased sensitivity to NN'-dicyclohexylcarbodi-imide, triethyltin and venturicidin was also observed during the early stage of glucose de-repression. 5. Smaller increases in sensitivity to efrapeptin, aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diaz-le, quercetin and spegazzinine also occurred. 6. The ATPase of glycerol-grown cells was less sensitive to inhibitors than that of glucose-repressed cells; change in values for I50 were not so marked during the growth cycle of cells growing with glycerol. 7. When submitochondrial particles from glycerol-grown cells were tested by passage through Sephadex G-50, a fourfold increase in activity was accompanied by increased inhibitor resistance. 8. Gel filtration of submitochondrial particles from glucose-de-repressed cells gave similar results, whereas loss of ATPase occurred in submitochondrial particles from glucose-repressed cells. 9. It is proposed that alterations in sensitivity to inhibitors at different stages of glucose derepression may be partly controlled by a naturally occuring inhibitor of ATPase. 10. The inhibitors tested may be classififed into two groups on the basis of alterations of sensitivity of the ATPase during physiological modification: (a) oligomycin, Dio-9, NN'-dicyclohexylcarbodi-imide, venturicidin and triethyltin, and (b) efrapeptin, aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, quercetin and spegazzinine.", "contents": "Mitochondrial adenosine triphosphatase of the fission yeast, Schizosaccharomyces pombe 972h-. Changes in activity and inhibitor-sensitivity in response to catabolite repression. 1. The specific activity of mitochondrial ATPase (adenosine triphosphatase) in extracts of Schizosaccharomyces pombe decreased 2.5-fold as the glucose concentration in the growth medium decreased from 50mM to 15mM. 2. During the late exponential phase of growth, ATPase activity doubled. 3. Sensitivity to oligomycin and Dio-9 as measured by values for I50(mug of inhibitor/mg of protein giving 50% inhibition) at pH 6.8 increased sixfold and ninefold respectively during the initial decrease in ATPase activity, and this degree of sensitivity was maintained for the remainder of the growth cycle. 4. Increased sensitivity to NN'-dicyclohexylcarbodi-imide, triethyltin and venturicidin was also observed during the early stage of glucose de-repression. 5. Smaller increases in sensitivity to efrapeptin, aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diaz-le, quercetin and spegazzinine also occurred. 6. The ATPase of glycerol-grown cells was less sensitive to inhibitors than that of glucose-repressed cells; change in values for I50 were not so marked during the growth cycle of cells growing with glycerol. 7. When submitochondrial particles from glycerol-grown cells were tested by passage through Sephadex G-50, a fourfold increase in activity was accompanied by increased inhibitor resistance. 8. Gel filtration of submitochondrial particles from glucose-de-repressed cells gave similar results, whereas loss of ATPase occurred in submitochondrial particles from glucose-repressed cells. 9. It is proposed that alterations in sensitivity to inhibitors at different stages of glucose derepression may be partly controlled by a naturally occuring inhibitor of ATPase. 10. The inhibitors tested may be classififed into two groups on the basis of alterations of sensitivity of the ATPase during physiological modification: (a) oligomycin, Dio-9, NN'-dicyclohexylcarbodi-imide, venturicidin and triethyltin, and (b) efrapeptin, aurovertin, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, quercetin and spegazzinine."}
{"id": "PMID:12754", "title": "Oxygen toxicity in the perfused rat liver and lung under hyperbaric conditions.", "content": "1. In the lung and liver of tocopherol-deficient rats, the activities of glutathione peroxidase and glucose 6-phosphate dehydrogenase were increased substantially, suggesting an important role for both enzymes in protecting the organ against the deleterious effects of lipid peroxides. 2. Facilitation of the glutathione peroxidase reaction by infusing t-butyl hydroperoxide caused the oxidation of nicotinamide nucleotides and glutathione, resulting in a concomitant increase in the rate of release of oxidized glutathione into the perfusate. Thus the rate of production of lipid peroxide and H2O2 in the perfused organ could be compared by simultaneous measurement of the rate of glutathione release and the turnover number of the catalase reaction. 3. On hyperbaric oxygenation at 4 X 10(5)Pa, H2O2 production, estimated from the turnover of the catalase reaction, was increased slightly in the liver, and glutathione release was increased slightly, in both lung and liver. 4. Tocopherol deficiency caused a marked increase in lipid-peroxide formation as indicated by a corresponding increase in glutathione release under hyperbaric oxygenation, with a further enhancement when the tocopherol-deficient rats were also starved. 5. The study demonstrates that the primary response to hyperbaric oxygenation is an elevation of the rate of lipid peroxidation rather than of the rate of formation of H2O2 or superoxide.", "contents": "Oxygen toxicity in the perfused rat liver and lung under hyperbaric conditions. 1. In the lung and liver of tocopherol-deficient rats, the activities of glutathione peroxidase and glucose 6-phosphate dehydrogenase were increased substantially, suggesting an important role for both enzymes in protecting the organ against the deleterious effects of lipid peroxides. 2. Facilitation of the glutathione peroxidase reaction by infusing t-butyl hydroperoxide caused the oxidation of nicotinamide nucleotides and glutathione, resulting in a concomitant increase in the rate of release of oxidized glutathione into the perfusate. Thus the rate of production of lipid peroxide and H2O2 in the perfused organ could be compared by simultaneous measurement of the rate of glutathione release and the turnover number of the catalase reaction. 3. On hyperbaric oxygenation at 4 X 10(5)Pa, H2O2 production, estimated from the turnover of the catalase reaction, was increased slightly in the liver, and glutathione release was increased slightly, in both lung and liver. 4. Tocopherol deficiency caused a marked increase in lipid-peroxide formation as indicated by a corresponding increase in glutathione release under hyperbaric oxygenation, with a further enhancement when the tocopherol-deficient rats were also starved. 5. The study demonstrates that the primary response to hyperbaric oxygenation is an elevation of the rate of lipid peroxidation rather than of the rate of formation of H2O2 or superoxide."}
{"id": "PMID:12755", "title": "Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats.", "content": "Plasma insulin concentrations in fed rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in adipose tissue and liver were estimated from the incorporation of 3H from 3H2O. In the adipose tissue dehydrogenase and acetyl-CoA carboxylase were evident. In liver, although changes in rates of fatty acid synthesis were found, the initial activity of pyruvate dehydrogenase did not alter, but small parallel changes in acetyl-CoA carboxylase activity were observed.", "contents": "Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Plasma insulin concentrations in fed rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in adipose tissue and liver were estimated from the incorporation of 3H from 3H2O. In the adipose tissue dehydrogenase and acetyl-CoA carboxylase were evident. In liver, although changes in rates of fatty acid synthesis were found, the initial activity of pyruvate dehydrogenase did not alter, but small parallel changes in acetyl-CoA carboxylase activity were observed."}
{"id": "PMID:12764", "title": "[Investigations on the Stability of Proscillaridine, Proscillaridine-3'-methylether and Proscillaridine-4'-methylether in Artificial Gastric and Intestinal Fluids (author's transl)].", "content": "The stability of bufadienolides in artificial gastric and intestinal fluids was investigated at different pH-values as a function of incubation time using proscillaridine, proscillaridine-3'-methylether and proscillaridine-4'-methylether. These glycosides were completely stable on pH 3.0--8.5 during the investigated time interval of 1 h. At lower pH-values cleavage of the glycosidic bond occurred. At pH 1.0 73% of proscillaridine, 33% of proscillaridine-3'-methylether and 41% of proscillaridine-4'-methylether were decomposed. At pH 2.0 only about 10% decomposition of these compounds could be detected. These experiments show that the stability of proscillaridine in gastric juice is comparable with the stability of digitalis glycosides and digoxin derivatives. The stability of methylated proscillaridine derivatives in artificial digestion fluids, however, proved to be superior to any orally administered cardiac glycoside.", "contents": "[Investigations on the Stability of Proscillaridine, Proscillaridine-3'-methylether and Proscillaridine-4'-methylether in Artificial Gastric and Intestinal Fluids (author's transl)]. The stability of bufadienolides in artificial gastric and intestinal fluids was investigated at different pH-values as a function of incubation time using proscillaridine, proscillaridine-3'-methylether and proscillaridine-4'-methylether. These glycosides were completely stable on pH 3.0--8.5 during the investigated time interval of 1 h. At lower pH-values cleavage of the glycosidic bond occurred. At pH 1.0 73% of proscillaridine, 33% of proscillaridine-3'-methylether and 41% of proscillaridine-4'-methylether were decomposed. At pH 2.0 only about 10% decomposition of these compounds could be detected. These experiments show that the stability of proscillaridine in gastric juice is comparable with the stability of digitalis glycosides and digoxin derivatives. The stability of methylated proscillaridine derivatives in artificial digestion fluids, however, proved to be superior to any orally administered cardiac glycoside."}
{"id": "PMID:12765", "title": "Piroxicam, a novel anti-inflammatory agent.", "content": "Piroxicam (CP-16 171) is a potent acidic anti-inflammatory agent structurally distinct from the current agents such as indometacin, phenylbutazone or naproxen. Pharmacokinetic studies indicate a longer plasma half-ife for piroxicam than for these agents. Potency in the range of indometacin is observed when piroxicam is tested in the carrageenan rat paw edema model. This activity is not dependent on an intact adrenocorticoid system. The high potency, long half-life and absence of cardiovascular or cental nervous system effects have encouraged clinical trial of piroxicam.", "contents": "Piroxicam, a novel anti-inflammatory agent. Piroxicam (CP-16 171) is a potent acidic anti-inflammatory agent structurally distinct from the current agents such as indometacin, phenylbutazone or naproxen. Pharmacokinetic studies indicate a longer plasma half-ife for piroxicam than for these agents. Potency in the range of indometacin is observed when piroxicam is tested in the carrageenan rat paw edema model. This activity is not dependent on an intact adrenocorticoid system. The high potency, long half-life and absence of cardiovascular or cental nervous system effects have encouraged clinical trial of piroxicam."}
{"id": "PMID:12766", "title": "Cardiorespiratory activitirs of 3-formylamino-4-hydroxy-alpha-(n-1-methyl-2-p-methoxyphenethylaminomethyl)-benzylalcohol-hemifumarate(BD 40A) and some other beta-adrenoceptor stimulants in conscious guinea pigs.", "content": "The beta-stimulant activity of 3-formylamino-4-hydroxy-alpha-(N-1-methoxyphenethylaminomethyl)-benzylalcohol-hemifumarate (BD 40A) was compared with those of isoproterenol, orciprenaline, trimetoquinol and salbutamol in conscious guinea pigs. Bronchodilator effects of BD 40A were most potent among five agonists by s.c., oral and aerosol administration, and were lasting by oral and aerosol administration. BD 40A was similar to isoproterenol, more potent than trimetoquinol, orciprenaline and salbutamol in increasing heart rate by s.c. route. The cardiostimulating effect of BD 40A was more potent than that of isoproterenol, trimetoquinol and salbutamol orally. However, the order of bronchoselectivity (ratio between ED30 beats/min vs. ED50) in conscious guinea pigs was salbutamol greater than BD 40A = trimetoquinol greater than orciprenaline greater than isoproterenol by s.c. administration, and by oral administration the order was BD 40A = salbutamol greater than trimetoquinol = isoproterenol. Orciprenaline showed no beta-stimulating effect in guinea pigs orally. In guinea pigs, BD 40A, like salbutamol, seems to be a beta2-adrenoceptor stimulant.", "contents": "Cardiorespiratory activitirs of 3-formylamino-4-hydroxy-alpha-(n-1-methyl-2-p-methoxyphenethylaminomethyl)-benzylalcohol-hemifumarate(BD 40A) and some other beta-adrenoceptor stimulants in conscious guinea pigs. The beta-stimulant activity of 3-formylamino-4-hydroxy-alpha-(N-1-methoxyphenethylaminomethyl)-benzylalcohol-hemifumarate (BD 40A) was compared with those of isoproterenol, orciprenaline, trimetoquinol and salbutamol in conscious guinea pigs. Bronchodilator effects of BD 40A were most potent among five agonists by s.c., oral and aerosol administration, and were lasting by oral and aerosol administration. BD 40A was similar to isoproterenol, more potent than trimetoquinol, orciprenaline and salbutamol in increasing heart rate by s.c. route. The cardiostimulating effect of BD 40A was more potent than that of isoproterenol, trimetoquinol and salbutamol orally. However, the order of bronchoselectivity (ratio between ED30 beats/min vs. ED50) in conscious guinea pigs was salbutamol greater than BD 40A = trimetoquinol greater than orciprenaline greater than isoproterenol by s.c. administration, and by oral administration the order was BD 40A = salbutamol greater than trimetoquinol = isoproterenol. Orciprenaline showed no beta-stimulating effect in guinea pigs orally. In guinea pigs, BD 40A, like salbutamol, seems to be a beta2-adrenoceptor stimulant."}
{"id": "PMID:12767", "title": "[The influence of pentagastrin on the ratios of Na+,K+H+/Amino acids in gastric juice. Short communication (author's transl)].", "content": "Pentagastrin has a distinct effect on the ratios of Na+,K+,H+/amino acid in the gastric juice in the different states of acidity. Contrary to the ratios of normacidity the values of all quotients in patients with hyper-, hypo- and anacidity are significantly reduced.", "contents": "[The influence of pentagastrin on the ratios of Na+,K+H+/Amino acids in gastric juice. Short communication (author's transl)]. Pentagastrin has a distinct effect on the ratios of Na+,K+,H+/amino acid in the gastric juice in the different states of acidity. Contrary to the ratios of normacidity the values of all quotients in patients with hyper-, hypo- and anacidity are significantly reduced."}
{"id": "PMID:12768", "title": "[Profile of pharmacological actions of NAB 365 (clenbuterol), a novel broncholytic agent with selective activity on adrenergic beta2-receptors (author's transl)].", "content": "Effects of 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) on the adrenergic beta-receptors were investigated and compared with those of isoproterenol and salbutamol. The beta2-mimetic activity of clenbuterol on the smooth muscle of bronchi, uterus and vessels after i.v. injection corresponds to that of salbutamol in all laboratory animals. When given subcutaneously or as an aerosol clenbuterol is even somewhat more effective than isoproterenol. Clenbuterol differs from the known beta-mimetic drugs in its much longer duration of action. Therefore the integral of activity of single doses of clenbuterol, which are equally effective in the period of their maximal action, is remarkably greater than that of the other beta-mimetic substances. Clenbuterol differs from known beta-mimetic drugs used as bronchodilators in its efficacy after oral administration and in its mode of action on the heart. In the isolated auricle of the rabbit it has proved to be a weak partial agonist. In conscious rabbits, anesthetised guinea-pigs, dogs and cats the maximum of tachycardia obtainable by clenbuterol is lower than that of salbutamol. The higher degree of tachycardia in conscious dogs provoked by clenbuterol is a result of a reflex reaction to the vasodilation analogous to that of salbutamol. In higher doses clenbuterol shows beta1-blocking properties. Like other beta-blocking agents it owns qualities of a local-anesthetic and prolongs refractory period of the heart of guinea-pigs. In contrast to other beta-mimetic substances, clenbuterol causes only slight mobilization of heart muscle glycogen by doses higher than those which have broncholytic effects. The lipolytic and lactacidemia inducing activity of clenbuterol in rabbits corresponds to that of isoproterenol. The blood sugar is only slightly increased by clenbuterol as well as by other beta-mimetic agents. Degree and duration of action of clenbuterol and the other sympathomimetic amines on skeletal muscle of the cat shows parallelism with that of the broncholytic effect. In the rat clenbuterol inhibits the gastric secretion more than does isoproterenol. In contrast to other broncholytic substances, a very small dosage of clenbuterol is sufficient to protect rats against the liberation of histamine and serotonin caused by the anaphylactic reaction.", "contents": "[Profile of pharmacological actions of NAB 365 (clenbuterol), a novel broncholytic agent with selective activity on adrenergic beta2-receptors (author's transl)]. Effects of 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) on the adrenergic beta-receptors were investigated and compared with those of isoproterenol and salbutamol. The beta2-mimetic activity of clenbuterol on the smooth muscle of bronchi, uterus and vessels after i.v. injection corresponds to that of salbutamol in all laboratory animals. When given subcutaneously or as an aerosol clenbuterol is even somewhat more effective than isoproterenol. Clenbuterol differs from the known beta-mimetic drugs in its much longer duration of action. Therefore the integral of activity of single doses of clenbuterol, which are equally effective in the period of their maximal action, is remarkably greater than that of the other beta-mimetic substances. Clenbuterol differs from known beta-mimetic drugs used as bronchodilators in its efficacy after oral administration and in its mode of action on the heart. In the isolated auricle of the rabbit it has proved to be a weak partial agonist. In conscious rabbits, anesthetised guinea-pigs, dogs and cats the maximum of tachycardia obtainable by clenbuterol is lower than that of salbutamol. The higher degree of tachycardia in conscious dogs provoked by clenbuterol is a result of a reflex reaction to the vasodilation analogous to that of salbutamol. In higher doses clenbuterol shows beta1-blocking properties. Like other beta-blocking agents it owns qualities of a local-anesthetic and prolongs refractory period of the heart of guinea-pigs. In contrast to other beta-mimetic substances, clenbuterol causes only slight mobilization of heart muscle glycogen by doses higher than those which have broncholytic effects. The lipolytic and lactacidemia inducing activity of clenbuterol in rabbits corresponds to that of isoproterenol. The blood sugar is only slightly increased by clenbuterol as well as by other beta-mimetic agents. Degree and duration of action of clenbuterol and the other sympathomimetic amines on skeletal muscle of the cat shows parallelism with that of the broncholytic effect. In the rat clenbuterol inhibits the gastric secretion more than does isoproterenol. In contrast to other broncholytic substances, a very small dosage of clenbuterol is sufficient to protect rats against the liberation of histamine and serotonin caused by the anaphylactic reaction."}
{"id": "PMID:12769", "title": "Synthetic analgesics: N-(1-[2-arylethyl]-4-substituted 4-piperidinyl) N-arylalkanamides.", "content": "The synthesis of several 4-arylamino-4-piperdinecarboxylic acids is reported. These acids were starting materials for the preparation of alpha-amino esthers, ethers and ketones. Different synthetic approaches are described. Suitable substitution on both nitrogen atoms afforded extremely potent analgesics. Thus, methyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate (22),N-(4-(methoxymethyl)-2-[2-(2-thienyl)ethyl]-4-piperidinyl)-N-phenylpropranamide (67) and N-[4-acetyl-1-(2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide (82) were found to be respectively 7682, 3987 and 4921 times as potent as morfine. Both cis- and trans-3-methyl homologs of 22 have been prepared. As expected, analgesic activity resides mainly in the cis-isomer.", "contents": "Synthetic analgesics: N-(1-[2-arylethyl]-4-substituted 4-piperidinyl) N-arylalkanamides. The synthesis of several 4-arylamino-4-piperdinecarboxylic acids is reported. These acids were starting materials for the preparation of alpha-amino esthers, ethers and ketones. Different synthetic approaches are described. Suitable substitution on both nitrogen atoms afforded extremely potent analgesics. Thus, methyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate (22),N-(4-(methoxymethyl)-2-[2-(2-thienyl)ethyl]-4-piperidinyl)-N-phenylpropranamide (67) and N-[4-acetyl-1-(2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide (82) were found to be respectively 7682, 3987 and 4921 times as potent as morfine. Both cis- and trans-3-methyl homologs of 22 have been prepared. As expected, analgesic activity resides mainly in the cis-isomer."}
{"id": "PMID:12770", "title": "In vitro effects of bencyclan on coagulation, fibrinolysis and platelet function.", "content": "The in vitro effects of N-3-(1-benzyl-cycloheptyloxy)-propyl-N,N-dimethylammonium-hydrogenfumarate (bencyclan) on clotting, fibrinolytic and platelet function test were investigated by adding the drug to normal human plasma. An anticoagulant activity, mainly of an antithromboplastin nature (directed against later stages of intrinsic thromboplastin formation and against tissue thromboplastin), was observed, while thrombin phase was unaffected. No effect was found in the fibrinolytic system tested (euglobulin lysis, UK-activated fibrinolysis, \"hanging clot\" method). The drug, although capable of aggregating platelets by itself at very high concentrations, showed a striking inhibitory effect, over a wide range of concentrations, both on platelet aggregation induced by ADP, epinephrine or collagen and on platelet adhesiveness to glass or collagen. Clot retraction was also clearly inhibited. PF3 availability was influenced with a peculiar two-phase behaviour dose-dependently. High concentrations showed a promoting action, while the lower were obviously inhibitory. It is suggested that the effects on platelet function may be due to an influence of the drug on cell membrane.", "contents": "In vitro effects of bencyclan on coagulation, fibrinolysis and platelet function. The in vitro effects of N-3-(1-benzyl-cycloheptyloxy)-propyl-N,N-dimethylammonium-hydrogenfumarate (bencyclan) on clotting, fibrinolytic and platelet function test were investigated by adding the drug to normal human plasma. An anticoagulant activity, mainly of an antithromboplastin nature (directed against later stages of intrinsic thromboplastin formation and against tissue thromboplastin), was observed, while thrombin phase was unaffected. No effect was found in the fibrinolytic system tested (euglobulin lysis, UK-activated fibrinolysis, \"hanging clot\" method). The drug, although capable of aggregating platelets by itself at very high concentrations, showed a striking inhibitory effect, over a wide range of concentrations, both on platelet aggregation induced by ADP, epinephrine or collagen and on platelet adhesiveness to glass or collagen. Clot retraction was also clearly inhibited. PF3 availability was influenced with a peculiar two-phase behaviour dose-dependently. High concentrations showed a promoting action, while the lower were obviously inhibitory. It is suggested that the effects on platelet function may be due to an influence of the drug on cell membrane."}
{"id": "PMID:12771", "title": "N-4-Substituted 1-(2-arylethyl)-4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin.", "content": "The intravenous analgesic activity and toxicity of a novel series of N-[4-substituted 1-(2-arylethyl)-4-piperidinyl]-N-phenylpropanamides was studied in rats. Onset, potency and duration of analgesic action were assessed in the tail withdrawal test and compared with the activity of fentanyl, (+)-cis-3-methylfentanyl (R 26 800), morphine, and pethidine. All compounds studied were found to be extremely potent analgesics characterized by an unusually high safety margin. Methyl 4-[N-(1-oxopropyl)-N-phenyl-amino]-1-(2-phenylethyl)-4-piperidinecarboxylate (R 31 833; lowest ED50 = 0.00032 mg/kg) is the most potent compound (10 031 times morphine). cis-Methyl 3-methyl-4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidine carboxylate (R 32 792) is the longest acting compound (more than 8 h at 4 times the lowest ED50) and N-[4-(1-oxopropyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide (R 33 352) is the shortest acting compound (0.74 h at 4 times the lowest ED50) of the 4-substituted fentanyl derivatives. N-[4-(Methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide (R 30 730) was selected for further investigation. R 30 730 has a rapid onset of action and is 4521 times more potent than morphine at the time of peak effect; it has a relatively short duration of action comparable to that of fentanyl and its safety margin (LD50/lowest ED50 = 25 211) is unusually high.", "contents": "N-4-Substituted 1-(2-arylethyl)-4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin. The intravenous analgesic activity and toxicity of a novel series of N-[4-substituted 1-(2-arylethyl)-4-piperidinyl]-N-phenylpropanamides was studied in rats. Onset, potency and duration of analgesic action were assessed in the tail withdrawal test and compared with the activity of fentanyl, (+)-cis-3-methylfentanyl (R 26 800), morphine, and pethidine. All compounds studied were found to be extremely potent analgesics characterized by an unusually high safety margin. Methyl 4-[N-(1-oxopropyl)-N-phenyl-amino]-1-(2-phenylethyl)-4-piperidinecarboxylate (R 31 833; lowest ED50 = 0.00032 mg/kg) is the most potent compound (10 031 times morphine). cis-Methyl 3-methyl-4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidine carboxylate (R 32 792) is the longest acting compound (more than 8 h at 4 times the lowest ED50) and N-[4-(1-oxopropyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide (R 33 352) is the shortest acting compound (0.74 h at 4 times the lowest ED50) of the 4-substituted fentanyl derivatives. N-[4-(Methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide (R 30 730) was selected for further investigation. R 30 730 has a rapid onset of action and is 4521 times more potent than morphine at the time of peak effect; it has a relatively short duration of action comparable to that of fentanyl and its safety margin (LD50/lowest ED50 = 25 211) is unusually high."}
{"id": "PMID:12772", "title": "Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs.", "content": "Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, is a chemically novel, highly potent and extremely safe intravenous morphine-like agent in laboratory animals. In mice R 30 730 i.v. is 2304 times more potent than morphine (hot plate ED50's: 0.0028 and 6.45 mg/kg, respectively). The i.v. safety margin of R 30 730 in mice is 1 : 6 679 (LD50 = 18.7 mg/kg). Under the same experimental conditions the safety margin of pethidine is 1 : 7.97, of morphine 1 : 34.9 and of fentanyl 1 : 454. In rats R 30 730 i.v. is 4521 times more potent than morphine (tail withdrawal test ED50's: 0.00071 and 3.21 mg/kg, respectively). The i.v. safety margin of R 30 730 in rats is 1 : 25 211 (LD50 : 17.9 mg/kg). Under the latter experimental conditions the safety margin of pethidine is 1 : 4.80, of morphine 1 : 69.5 and of fentanyl 1 : 277. In dogs R 30 730 i.v. is 2429 times more potent than morphine (apomorphine antagonism test ED50's: 0.00028 and 0.68 mg/kg, respectively). The i.v. safety margin in dogs is approximately 1 : 50 000, the LD50 being +/- 14.0 mg/kg. All morphine-like effects of R 30 730 are immediately antagonized by nalorphine. These pharmacological findings are relevant in connection to the increasing interest for use of morphinomimetics in anesthesia.", "contents": "Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs. Sufentanil (R 30 730), N-[4-methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide, is a chemically novel, highly potent and extremely safe intravenous morphine-like agent in laboratory animals. In mice R 30 730 i.v. is 2304 times more potent than morphine (hot plate ED50's: 0.0028 and 6.45 mg/kg, respectively). The i.v. safety margin of R 30 730 in mice is 1 : 6 679 (LD50 = 18.7 mg/kg). Under the same experimental conditions the safety margin of pethidine is 1 : 7.97, of morphine 1 : 34.9 and of fentanyl 1 : 454. In rats R 30 730 i.v. is 4521 times more potent than morphine (tail withdrawal test ED50's: 0.00071 and 3.21 mg/kg, respectively). The i.v. safety margin of R 30 730 in rats is 1 : 25 211 (LD50 : 17.9 mg/kg). Under the latter experimental conditions the safety margin of pethidine is 1 : 4.80, of morphine 1 : 69.5 and of fentanyl 1 : 277. In dogs R 30 730 i.v. is 2429 times more potent than morphine (apomorphine antagonism test ED50's: 0.00028 and 0.68 mg/kg, respectively). The i.v. safety margin in dogs is approximately 1 : 50 000, the LD50 being +/- 14.0 mg/kg. All morphine-like effects of R 30 730 are immediately antagonized by nalorphine. These pharmacological findings are relevant in connection to the increasing interest for use of morphinomimetics in anesthesia."}
{"id": "PMID:12773", "title": "[Blood gas analytical study on cerebral circulation under the influence of dihydroergotoxin (author's transl)].", "content": "The demand for sufficient blood supply and oxygenation of cerebral tissue after brain surgery or severe head injuries requires the clinical investigation of drugs which are supposed to improve cerebral blood flow and metabolism. We have therefore used the hydrogenated derivatives of the ergotoxin components of the secale alcaloids in the post-operative and posttraumatic period of neurosurgical patients, respectively, and studied their effect on cerebral metabolism by successive analysis of blood gases in the arterial and venous blood. A significant increase of cerebral venous CO2-concentration following the administration of dihydroergotoxin in these patients in all probability is attributable to an improved O2-utilisation in the cerebral tissue.", "contents": "[Blood gas analytical study on cerebral circulation under the influence of dihydroergotoxin (author's transl)]. The demand for sufficient blood supply and oxygenation of cerebral tissue after brain surgery or severe head injuries requires the clinical investigation of drugs which are supposed to improve cerebral blood flow and metabolism. We have therefore used the hydrogenated derivatives of the ergotoxin components of the secale alcaloids in the post-operative and posttraumatic period of neurosurgical patients, respectively, and studied their effect on cerebral metabolism by successive analysis of blood gases in the arterial and venous blood. A significant increase of cerebral venous CO2-concentration following the administration of dihydroergotoxin in these patients in all probability is attributable to an improved O2-utilisation in the cerebral tissue."}
{"id": "PMID:12774", "title": "Failure of benzoctamine to influence the activity of rat striatum tyrosine-hydroxylase.", "content": "The influence of benzoctamine (Tacitin) on rat striatum tyrosine-hydroxylase was analized. Injection of 100 mg benzoctamine/kg body weight caused no alteration in the tyrosine-hydroxylase activity whilst a decrease of about 60% in the activity was recorded after treatment with a-methyl-p-tyrosine a known inhibitor of tyrosine-hydroxylase. The present results differ from those of Maitre et al. which indicated that benzoctamine inhibited tyrosine-hydroxylase activity.", "contents": "Failure of benzoctamine to influence the activity of rat striatum tyrosine-hydroxylase. The influence of benzoctamine (Tacitin) on rat striatum tyrosine-hydroxylase was analized. Injection of 100 mg benzoctamine/kg body weight caused no alteration in the tyrosine-hydroxylase activity whilst a decrease of about 60% in the activity was recorded after treatment with a-methyl-p-tyrosine a known inhibitor of tyrosine-hydroxylase. The present results differ from those of Maitre et al. which indicated that benzoctamine inhibited tyrosine-hydroxylase activity."}
{"id": "PMID:12778", "title": "Pharmacological basis for antihypertensive effects of intravenous labetalol.", "content": "Labetalol 1-5 mg/kg administered intravenously to normal subjects in the supine position produced an immediate mean fall in systolic (16%) and diastolic (25%) blood pressure with a concomitant increase in heart rate (12%). After graded exercise, intravenous labetalol inhibited increases in heart rate and blood pressure. Isoprenaline log dose response curves of increase in heart rate and reduction in diastolic pressure after intravenous labetalol shifted to the right in a parallel manner compared with pre-labetalol response curves suggestive of competitive antagonism at beta-adrenoceptor sites. Similarly, phenylephrine dose response curves of increase in systolic pressure before and after intravenous labetalol were suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of relative potency alpha: beta adrenoceptor antagonism after intravenous labetalol was approximately 1:7, whereas in the same subjects after oral labetalol the ratio was approximately 1:3 as previously reported. Using the inhibition of isoprenaline tachycardia to estimate the potency of the beta-adrenoceptor antagonism of labetalol relative to that of propranolol the potency ratio was 1:6. However, using inhibition of Valsalva tachycardia as the index, the estimated ratio was approximately 1:3. Estimates of relative potency using inhibition of tilt tachycardia were complicated by the additional effects upon blood pressure after labetalol not seen after propranolol. Labetalol produced adrenoceptor blockade at both alpha and beta sites in man sufficient to explain its therapeutic antihypertensive effect.", "contents": "Pharmacological basis for antihypertensive effects of intravenous labetalol. Labetalol 1-5 mg/kg administered intravenously to normal subjects in the supine position produced an immediate mean fall in systolic (16%) and diastolic (25%) blood pressure with a concomitant increase in heart rate (12%). After graded exercise, intravenous labetalol inhibited increases in heart rate and blood pressure. Isoprenaline log dose response curves of increase in heart rate and reduction in diastolic pressure after intravenous labetalol shifted to the right in a parallel manner compared with pre-labetalol response curves suggestive of competitive antagonism at beta-adrenoceptor sites. Similarly, phenylephrine dose response curves of increase in systolic pressure before and after intravenous labetalol were suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of relative potency alpha: beta adrenoceptor antagonism after intravenous labetalol was approximately 1:7, whereas in the same subjects after oral labetalol the ratio was approximately 1:3 as previously reported. Using the inhibition of isoprenaline tachycardia to estimate the potency of the beta-adrenoceptor antagonism of labetalol relative to that of propranolol the potency ratio was 1:6. However, using inhibition of Valsalva tachycardia as the index, the estimated ratio was approximately 1:3. Estimates of relative potency using inhibition of tilt tachycardia were complicated by the additional effects upon blood pressure after labetalol not seen after propranolol. Labetalol produced adrenoceptor blockade at both alpha and beta sites in man sufficient to explain its therapeutic antihypertensive effect."}
{"id": "PMID:12775", "title": "Diffusion coefficients for protein molecules in blood serum.", "content": "A new technique is described for the measurement of the self-diffusion coefficients of protein macromolecules in solution. The method makes use of the phenomenon of Taylor dispersion of a solute introduced into a solvent flowing in the laminar regime through a tube of circular section. Results are reported for the self-diffusion coefficient of cholesterol associated with lipoprotein molecules in dogs' serum at pH 7.4 in the temperature range 18-37 degrees C. The diffusivity of bovine serum albumin in serum has also been studied as a function of temperature at pH 7.4 and 4.7. In the more basic solution, measurements of the diffusivity as a function of protein concentration substantially agree with earlier work. For all the systems studied the diffusivity varies rapidly with temperature. The pH of the solution, in the case of bovine serum albumin, also has a significant effect on the diffusivity of the macromolecule. The latter observation is related to the amount of water bound to the protein molecule in solution.", "contents": "Diffusion coefficients for protein molecules in blood serum. A new technique is described for the measurement of the self-diffusion coefficients of protein macromolecules in solution. The method makes use of the phenomenon of Taylor dispersion of a solute introduced into a solvent flowing in the laminar regime through a tube of circular section. Results are reported for the self-diffusion coefficient of cholesterol associated with lipoprotein molecules in dogs' serum at pH 7.4 in the temperature range 18-37 degrees C. The diffusivity of bovine serum albumin in serum has also been studied as a function of temperature at pH 7.4 and 4.7. In the more basic solution, measurements of the diffusivity as a function of protein concentration substantially agree with earlier work. For all the systems studied the diffusivity varies rapidly with temperature. The pH of the solution, in the case of bovine serum albumin, also has a significant effect on the diffusivity of the macromolecule. The latter observation is related to the amount of water bound to the protein molecule in solution."}
{"id": "PMID:12776", "title": "[Acid-base equilibrium in healthy newborns. Pattern of normality in Mexico City].", "content": "During their spontaneous recovery after birth, the acid-base balance was studied in 32 healthy newborns. The observation period lasted for 4 hours. Determinations were carried out, both in umbilical vessels as in central arterial blood. The most outstanding phenomenon was an increase in acidosis at 30 minutes of life. The metabolic component predominating over the respiratory was a definitely evident fact. At the end of four hours, the acid-base balance reached figures considered normal for the adult.", "contents": "[Acid-base equilibrium in healthy newborns. Pattern of normality in Mexico City]. During their spontaneous recovery after birth, the acid-base balance was studied in 32 healthy newborns. The observation period lasted for 4 hours. Determinations were carried out, both in umbilical vessels as in central arterial blood. The most outstanding phenomenon was an increase in acidosis at 30 minutes of life. The metabolic component predominating over the respiratory was a definitely evident fact. At the end of four hours, the acid-base balance reached figures considered normal for the adult."}
{"id": "PMID:12780", "title": "The effects of Bordetella pertussis vaccine on cerebral vascular permeability.", "content": "The effect of Bordetella pertussis vaccine on the cerebral vascular permeability in the mouse was studied by a radio-isotope method (131I-labelled HSA). Intravenous injection of 4 x 1010 heat-killed pertussis organisms caused a measurable increase in permeability in normal mice. Cryoinjury to the cerebral hemispheres resulted in a striking increase in vascular permeability at 24 h. This declined within 48 h and stabilized at a level fractionally higher than normal at 7 days (\"healed lesion\"). When pertussis organisms were injected into mice bearing (\"healed lesion\"). When pertussis organisms were injected into mice bearing \"healed lesions\" the increase in permeability was similar in magnitude to that in uninjured brain. The effect was increased by a second administration of pertussis 24 h after the first. The action of pertussis on a newly inflicted cryoinjury was protective. It is suggested that permeability changes in the cerebral vessels may be involved in the evolution of the encephalopathy attributed to the use of Bordetella pertussis vaccine in man.", "contents": "The effects of Bordetella pertussis vaccine on cerebral vascular permeability. The effect of Bordetella pertussis vaccine on the cerebral vascular permeability in the mouse was studied by a radio-isotope method (131I-labelled HSA). Intravenous injection of 4 x 1010 heat-killed pertussis organisms caused a measurable increase in permeability in normal mice. Cryoinjury to the cerebral hemispheres resulted in a striking increase in vascular permeability at 24 h. This declined within 48 h and stabilized at a level fractionally higher than normal at 7 days (\"healed lesion\"). When pertussis organisms were injected into mice bearing (\"healed lesion\"). When pertussis organisms were injected into mice bearing \"healed lesions\" the increase in permeability was similar in magnitude to that in uninjured brain. The effect was increased by a second administration of pertussis 24 h after the first. The action of pertussis on a newly inflicted cryoinjury was protective. It is suggested that permeability changes in the cerebral vessels may be involved in the evolution of the encephalopathy attributed to the use of Bordetella pertussis vaccine in man."}
{"id": "PMID:12781", "title": "Inhibition of the liver and plasma protein acute-phase response in mice by D-galactosamine.", "content": "Local inflammation evoked in Swiss albino mice by subcutaneous injection of Celite resulted in a rise of liver tyrosine aminotransferase activity and plasma level of fibrinogen and seromucoid, while liver alanine aminotransferase activity and plasma level of fibrinogen and seromucoid, while liver alanine aminotransferase activity and the plasma level of albumin and total protein remained unaltered. By measuring the incorporation of [14C] leucine, stimulation of liver and plasms protein synthesis by Celite injection was demonstrated. Administration of D-galactosamine (2-5 mg/10 g body weight) inhibited the enhanced synthesis of liver proteins, and especially of trauma-induced synthesis of plasma fibrinogen and seromucoid. The inhibitory effect of galactosamine was most pronounced when the amino sugar was injected simultaneously with Celite and then protein synthesis was measured 6 h later. The results obtained support the idea that high doses of galactosamine inhibit transcription of trauma-inducible mRNA in the liver and thus block the acute-phase response.", "contents": "Inhibition of the liver and plasma protein acute-phase response in mice by D-galactosamine. Local inflammation evoked in Swiss albino mice by subcutaneous injection of Celite resulted in a rise of liver tyrosine aminotransferase activity and plasma level of fibrinogen and seromucoid, while liver alanine aminotransferase activity and plasma level of fibrinogen and seromucoid, while liver alanine aminotransferase activity and the plasma level of albumin and total protein remained unaltered. By measuring the incorporation of [14C] leucine, stimulation of liver and plasms protein synthesis by Celite injection was demonstrated. Administration of D-galactosamine (2-5 mg/10 g body weight) inhibited the enhanced synthesis of liver proteins, and especially of trauma-induced synthesis of plasma fibrinogen and seromucoid. The inhibitory effect of galactosamine was most pronounced when the amino sugar was injected simultaneously with Celite and then protein synthesis was measured 6 h later. The results obtained support the idea that high doses of galactosamine inhibit transcription of trauma-inducible mRNA in the liver and thus block the acute-phase response."}
{"id": "PMID:12782", "title": "Atenolol versus propranolol. A comparison of ocular hypotensive effect of an oral dose.", "content": "In a controlled double-blind cross-over trial in 10 patients comprising six with open-angle glaucoma, three with closed-angle glaucoma, and one with ocular hypertension, a single oral dose of atenolol (50 mg) was significantly more effective than propranolol (40 mg) in reducing ocular tension.", "contents": "Atenolol versus propranolol. A comparison of ocular hypotensive effect of an oral dose. In a controlled double-blind cross-over trial in 10 patients comprising six with open-angle glaucoma, three with closed-angle glaucoma, and one with ocular hypertension, a single oral dose of atenolol (50 mg) was significantly more effective than propranolol (40 mg) in reducing ocular tension."}
{"id": "PMID:12783", "title": "Milk-substitute diet composition and abomasal secretion in the calf.", "content": "1. The effect of different protein sources in milk-substitute diets on abomasal acidity and proteolytic activity was studied in Friesian calves, aged 20-58 d (Expt 1). The diets contained 'mildly' preheated, spray-dried skim-milk powder (MHM), severely preheated, spray-dried skim-milk powder (SHM), fish-protein concentrate (FPC) or solvent-extracted soya-bean flour (SF) as the main protein source. 2. Gastric juice was collected from abomasal pouches before feeding and at 15 min intervals for 8 h after the morning feed. Samples of digesta were obtained from the abomasum at 1 h intervals during the same period. 3. Digesta pH was lower and titratable acidity higher 0-3 after giving the diet containing MHM than when any of the other three diets was given. 3. Acid secretion from the pouches for the different diets was in the order: FPC greater than MHM greater than SHM greater than or equal to SF. 5. Protease secretion from the pouches, assayed at pH 2-1, was in the order: MHM greater than SHM = FPC greater than SF. 6. The effect of dry matter (DM) intake and concentration on abomasal acidity was also studied in calves given diets which contained MHM (Expt 2). This diet was reconstituted at either 100 or 149 g DM/kg liquid diet and fed at either 32-5 or 49-0 g DM/kg live weight 0-75 per d. Samples of abomasal digesta were collected as in Expt 1. 7. A high intake of DM at a low DM concentration resulted in low acidity of the digesta in the first 3 h after feeding, which suggested a dilution effect. Comparison of two diets of different DM concentration, which were fed in the same volume of liquid, indicated that the greater the DM intake, the greater was the amount of acid secreted. 8. It is concluded that the protein sources varied in their ability to stimulate abomasal acid and protease secretion and it is suggested that this may relate to calf performance.", "contents": "Milk-substitute diet composition and abomasal secretion in the calf. 1. The effect of different protein sources in milk-substitute diets on abomasal acidity and proteolytic activity was studied in Friesian calves, aged 20-58 d (Expt 1). The diets contained 'mildly' preheated, spray-dried skim-milk powder (MHM), severely preheated, spray-dried skim-milk powder (SHM), fish-protein concentrate (FPC) or solvent-extracted soya-bean flour (SF) as the main protein source. 2. Gastric juice was collected from abomasal pouches before feeding and at 15 min intervals for 8 h after the morning feed. Samples of digesta were obtained from the abomasum at 1 h intervals during the same period. 3. Digesta pH was lower and titratable acidity higher 0-3 after giving the diet containing MHM than when any of the other three diets was given. 3. Acid secretion from the pouches for the different diets was in the order: FPC greater than MHM greater than SHM greater than or equal to SF. 5. Protease secretion from the pouches, assayed at pH 2-1, was in the order: MHM greater than SHM = FPC greater than SF. 6. The effect of dry matter (DM) intake and concentration on abomasal acidity was also studied in calves given diets which contained MHM (Expt 2). This diet was reconstituted at either 100 or 149 g DM/kg liquid diet and fed at either 32-5 or 49-0 g DM/kg live weight 0-75 per d. Samples of abomasal digesta were collected as in Expt 1. 7. A high intake of DM at a low DM concentration resulted in low acidity of the digesta in the first 3 h after feeding, which suggested a dilution effect. Comparison of two diets of different DM concentration, which were fed in the same volume of liquid, indicated that the greater the DM intake, the greater was the amount of acid secreted. 8. It is concluded that the protein sources varied in their ability to stimulate abomasal acid and protease secretion and it is suggested that this may relate to calf performance."}
{"id": "PMID:12784", "title": "Studies on lipid digestion in the preruminant calf. The source of lipolytic activity in the abomasum.", "content": "1. Lipolytic and proteolytic activities and pH values were determined in secretions collected from innervated abomasal pouches and in abomasal contents from preruminant calves given liquid diets. 2. No lipolytic activity was detected in pouch secretions collected during 1 h after feeding, though lipolytic activity was present in abomasal contents; pepsin (EC 3.4.23.1) and renin (EC 3.4.23.4) were present in both pouch secretions and abomasal contents. The pH values of pouch secretions ranged from 1-2 to 1-8 and those of abomasal contents from 4-2 to 5-9. 3. When diet was placed directly into the abomasal pouch soon after feeding, the pH values of pouch and abomasal contents decreased similarly (i.e. from 6-3 to approximately 5). Protease activity (U/ml) of pouch contents ranged from 0-1 to 0-8 and that of abomasal contents from 0-1 to 0-2. No lipolytic activity was detected in pouch contents, though abomasal contents contained 0-6 to 1-2 U/ml and when the diet contained milk-fat as the dietary fat source considerable lipolysis of triglycerides containing shorter-chain fatty acids was found. 4. It is concluded that there is no significant secretion of lipolytic enzymes by the fundal mucosa and that the lipolysis of triglycerides in the abomasum of the preruminant calf is due predominantly to a lipolytic enzyme in saliva.", "contents": "Studies on lipid digestion in the preruminant calf. The source of lipolytic activity in the abomasum. 1. Lipolytic and proteolytic activities and pH values were determined in secretions collected from innervated abomasal pouches and in abomasal contents from preruminant calves given liquid diets. 2. No lipolytic activity was detected in pouch secretions collected during 1 h after feeding, though lipolytic activity was present in abomasal contents; pepsin (EC 3.4.23.1) and renin (EC 3.4.23.4) were present in both pouch secretions and abomasal contents. The pH values of pouch secretions ranged from 1-2 to 1-8 and those of abomasal contents from 4-2 to 5-9. 3. When diet was placed directly into the abomasal pouch soon after feeding, the pH values of pouch and abomasal contents decreased similarly (i.e. from 6-3 to approximately 5). Protease activity (U/ml) of pouch contents ranged from 0-1 to 0-8 and that of abomasal contents from 0-1 to 0-2. No lipolytic activity was detected in pouch contents, though abomasal contents contained 0-6 to 1-2 U/ml and when the diet contained milk-fat as the dietary fat source considerable lipolysis of triglycerides containing shorter-chain fatty acids was found. 4. It is concluded that there is no significant secretion of lipolytic enzymes by the fundal mucosa and that the lipolysis of triglycerides in the abomasum of the preruminant calf is due predominantly to a lipolytic enzyme in saliva."}
{"id": "PMID:12785", "title": "Studies on digestion and absorption in the intestines of growing pigs. Measurements of the flow of digesta and pH.", "content": "1. Thirty-five pigs were fitted with single re-entrant cannulas in either the duodenum, jejunum or ileum. A further twenty-four pigs were used in a conventional digestibility trial. 2. Methods for collecting, sampling and returning digesta were developed. 3. A 'practical-type' diet and two purfied diets were used, fed twice daily. 4. Flow and pH of digesta were measured hourly in the duodenum and jejunum, and every 6 h in the ileum. 5. In the duodenum and jejunum there were clear flow responses to feeding, while such an effect was not found in the ileum where the flow-rate was much lower and more uniform than in the former sites. 6. In the duodenum and jejunum, and within 6 h periods in the ileum, there was considerable variation in the flow-rate between different pigs within each hour but there was less variation in pH. 7. The pattern of flow in the duodenum and jejunum was similar for each of the diets but the total flow and the average pH in 24 h differed significantly between diets. There were more digesta of a lower pH from the 'practical-type' diet than the purified diets. 8. The pH in the duodenum was highest after feeding and decreased with increasing time after feeding. In the jejunum and ileum the pH-varied over a much smaller range than in the duodenum. 9. Collections for 6 h periods appeared to be insufficiently long to predict the values obtained in 24 h collections with reasonable accuracy.", "contents": "Studies on digestion and absorption in the intestines of growing pigs. Measurements of the flow of digesta and pH. 1. Thirty-five pigs were fitted with single re-entrant cannulas in either the duodenum, jejunum or ileum. A further twenty-four pigs were used in a conventional digestibility trial. 2. Methods for collecting, sampling and returning digesta were developed. 3. A 'practical-type' diet and two purfied diets were used, fed twice daily. 4. Flow and pH of digesta were measured hourly in the duodenum and jejunum, and every 6 h in the ileum. 5. In the duodenum and jejunum there were clear flow responses to feeding, while such an effect was not found in the ileum where the flow-rate was much lower and more uniform than in the former sites. 6. In the duodenum and jejunum, and within 6 h periods in the ileum, there was considerable variation in the flow-rate between different pigs within each hour but there was less variation in pH. 7. The pattern of flow in the duodenum and jejunum was similar for each of the diets but the total flow and the average pH in 24 h differed significantly between diets. There were more digesta of a lower pH from the 'practical-type' diet than the purified diets. 8. The pH in the duodenum was highest after feeding and decreased with increasing time after feeding. In the jejunum and ileum the pH-varied over a much smaller range than in the duodenum. 9. Collections for 6 h periods appeared to be insufficiently long to predict the values obtained in 24 h collections with reasonable accuracy."}
{"id": "PMID:12787", "title": "Proton-dependent dissociation equilibrium of hemoglobin. 1. A 700-nanometer light-scattering study on horse methemoglobin in the pH range 4.8 to 7.2.", "content": "The effect of proton concentration upon the subunit dissociation of horse methemoglobin has been investigated at two ionic strengths by light scattering photometry at 700 nm. Differential refractometry revealed a slight but systematic decrease of the specific refractive index increment with decreasing protein concentration for solutions in dialytic equilibrium with the solvent. In the pH range 4.8-7.2 the dissociation can be described by a simple equilibrium between tetramers and dimers. The dissociation constant Kd of the met derivative is found to be very similar to those of the O2- and CO-ligated states. From the slope of a plot of log Kd vs. pH, the number of protons bound is n = 1.3 +/- 0.1 resulting from an increase in the pK values of two groups upon dissociation. These two groups must be identical because the dissociation is symmetrical.", "contents": "Proton-dependent dissociation equilibrium of hemoglobin. 1. A 700-nanometer light-scattering study on horse methemoglobin in the pH range 4.8 to 7.2. The effect of proton concentration upon the subunit dissociation of horse methemoglobin has been investigated at two ionic strengths by light scattering photometry at 700 nm. Differential refractometry revealed a slight but systematic decrease of the specific refractive index increment with decreasing protein concentration for solutions in dialytic equilibrium with the solvent. In the pH range 4.8-7.2 the dissociation can be described by a simple equilibrium between tetramers and dimers. The dissociation constant Kd of the met derivative is found to be very similar to those of the O2- and CO-ligated states. From the slope of a plot of log Kd vs. pH, the number of protons bound is n = 1.3 +/- 0.1 resulting from an increase in the pK values of two groups upon dissociation. These two groups must be identical because the dissociation is symmetrical."}
{"id": "PMID:12788", "title": "Proton-dependent dissociation equilibrium of hemoglobin. 2. Surface pressure measurements in monolayers of horse hemoglobin (III).", "content": "The molecular weight of hemoglobin (III) in monolayers on aqueous subsolutions has been determined by measuring the surface pressure as a function of the protein surface concentration. The dissociation equilibrium between tetrameric and dimeric hemoglobin (III) was determined for spread as well as adsorbed monolayers. The results were compared with analogous measurements in solution. It was found that the numerical value and the pH dependence of the dissociation constant were similar both in the bulk and in the surface phase of the solution. From these findings it was concluded that the native conformation of hemoglobin (III) is retained after adsorption at aqueous surface.", "contents": "Proton-dependent dissociation equilibrium of hemoglobin. 2. Surface pressure measurements in monolayers of horse hemoglobin (III). The molecular weight of hemoglobin (III) in monolayers on aqueous subsolutions has been determined by measuring the surface pressure as a function of the protein surface concentration. The dissociation equilibrium between tetrameric and dimeric hemoglobin (III) was determined for spread as well as adsorbed monolayers. The results were compared with analogous measurements in solution. It was found that the numerical value and the pH dependence of the dissociation constant were similar both in the bulk and in the surface phase of the solution. From these findings it was concluded that the native conformation of hemoglobin (III) is retained after adsorption at aqueous surface."}
{"id": "PMID:12789", "title": "Conformational characteristics of luliberin. Circular dichroism and fluorescence studies.", "content": "By circular dichroism and fluorescence spectroscopy, the conformation of luliberin (luteinizing hormone-releasing hormone) has been investigated under various conditions of pH and solvents. Several structural parameters have been defined which seem predominant for the maintenance of the hormone in some privileged conformation(s). Formation of an intramolecular hydrogen bond between CO (His) and NH (Ser) seems likely when dissolving the hormone in organic solvent such as dioxane. Energy transfer has been demonstrated between Tyr and Trp residues. Calculation of the energy-transfer efficiency at different pH's allowed us to estimate in the range of 10 A the distance which separates these residues. Evidence is also provided for a charge-transfer interaction between protonated histidine and tryptophan. These data suggest that, when luliberin has organized structure (under appropriate surrounding conditions), its conformational pattern would resemble that of beta-turn structure in which a beta bend would exist at the level of the aromatic residues.", "contents": "Conformational characteristics of luliberin. Circular dichroism and fluorescence studies. By circular dichroism and fluorescence spectroscopy, the conformation of luliberin (luteinizing hormone-releasing hormone) has been investigated under various conditions of pH and solvents. Several structural parameters have been defined which seem predominant for the maintenance of the hormone in some privileged conformation(s). Formation of an intramolecular hydrogen bond between CO (His) and NH (Ser) seems likely when dissolving the hormone in organic solvent such as dioxane. Energy transfer has been demonstrated between Tyr and Trp residues. Calculation of the energy-transfer efficiency at different pH's allowed us to estimate in the range of 10 A the distance which separates these residues. Evidence is also provided for a charge-transfer interaction between protonated histidine and tryptophan. These data suggest that, when luliberin has organized structure (under appropriate surrounding conditions), its conformational pattern would resemble that of beta-turn structure in which a beta bend would exist at the level of the aromatic residues."}
{"id": "PMID:12790", "title": "Conformational characteristics of luliberin. Luminescence properties at liquid-nitrogen temperature.", "content": "The luminescence properties (fluorescence and phosphorescence) of luliberin have been investigated at liquid-nitrogen temperature (77 K) in 50% ethylene glycolaqueous buffer at various pH's. Calculation of the energy-transfer efficiency between Trp and Tyr residues leads to an evaluation of the distance separating these residues. In alkaline medium, when tyrosine is ionized, a 100% transfer efficiency occurs from Trp to Tyr- at the singlet level and also from Tyr- to Trp at the triplet level indicating that the TRP-Tyr distance is less than about 5A. When luliberin is at pH 7.8 (or 4.5), transfer efficiency from Tyr to Trp at the singlet level is 85-90% which should correspond to a distance between Trp and Tyr of about 10-12 A. These results are discussed with respect to the role played by aromatic amino acids both in the hormone conformation and in the hormone biological potency. Moreover, comparison with the data obtained from fluorescence or circular dichroism studies at room temperature allows us to deduce some characteristics of luliberin conformation. Structure-activity relationships in the aromatic region of luliberin are also discussed.", "contents": "Conformational characteristics of luliberin. Luminescence properties at liquid-nitrogen temperature. The luminescence properties (fluorescence and phosphorescence) of luliberin have been investigated at liquid-nitrogen temperature (77 K) in 50% ethylene glycolaqueous buffer at various pH's. Calculation of the energy-transfer efficiency between Trp and Tyr residues leads to an evaluation of the distance separating these residues. In alkaline medium, when tyrosine is ionized, a 100% transfer efficiency occurs from Trp to Tyr- at the singlet level and also from Tyr- to Trp at the triplet level indicating that the TRP-Tyr distance is less than about 5A. When luliberin is at pH 7.8 (or 4.5), transfer efficiency from Tyr to Trp at the singlet level is 85-90% which should correspond to a distance between Trp and Tyr of about 10-12 A. These results are discussed with respect to the role played by aromatic amino acids both in the hormone conformation and in the hormone biological potency. Moreover, comparison with the data obtained from fluorescence or circular dichroism studies at room temperature allows us to deduce some characteristics of luliberin conformation. Structure-activity relationships in the aromatic region of luliberin are also discussed."}
{"id": "PMID:12791", "title": "Purification of adenovirus messenger ribonucleic acid by an aqueous polymer two-phase system.", "content": "An aqueous polymer phase system containing 6.3% (w/w) dextran and 3.5% (w/w) poly(ethylene glycol) in 10 mM phosphate buffer (pH 8.0) was developed to select RNA-DNA hybrids from unhybridized RNA. The top phase of this phase system, which contains DNA and the RNA-DNA hybrids, can be used to purify adenovirus messenger RNA both early and late in the infectious cycle. The hybrids can be melted by heat in the top phase and the messenger RNA selected by oligo(dT)cellulose chromatography whereupon the polymers and the DNA percolate and the polyadenylated messenger RNA absorb to the column. The isolated messenger RNA appears to be almost quantitatively recovered at a purity from 70 to 90% depending on the concentration of the specific messenger RNA in the starting material. Early and late viral messenger RNA were selected on the complementary strands of adenovirus DNA according to this procedure.", "contents": "Purification of adenovirus messenger ribonucleic acid by an aqueous polymer two-phase system. An aqueous polymer phase system containing 6.3% (w/w) dextran and 3.5% (w/w) poly(ethylene glycol) in 10 mM phosphate buffer (pH 8.0) was developed to select RNA-DNA hybrids from unhybridized RNA. The top phase of this phase system, which contains DNA and the RNA-DNA hybrids, can be used to purify adenovirus messenger RNA both early and late in the infectious cycle. The hybrids can be melted by heat in the top phase and the messenger RNA selected by oligo(dT)cellulose chromatography whereupon the polymers and the DNA percolate and the polyadenylated messenger RNA absorb to the column. The isolated messenger RNA appears to be almost quantitatively recovered at a purity from 70 to 90% depending on the concentration of the specific messenger RNA in the starting material. Early and late viral messenger RNA were selected on the complementary strands of adenovirus DNA according to this procedure."}
{"id": "PMID:12792", "title": "Intermediate states of actomyosin adenosine triphosphatase.", "content": "The early kinetic steps of actomyosin subfragment 1 (acto-S1) adenosine triphosphatase have been investigated by simultaneous monitoring of fluorescence and light scattering and also by observation of the time course of the production of phosphate. The results show that fluorescence enhancement occurs after the dissociation of actomyosin and that the rate of enhancement is similar to the maximum rate of enhancement for S1 alone, under similar conditions of pH and temperature. The maximum rate of the phosphate burst for acto S1 is also approximately the same as that for S1 alone. The maximum rates for fluorescence enhancement or phosphate formation are reached at much lower adenosine triphosphate concentrations for acto-S1 than for S1. An extension of the actomyosin scheme is presented which accounts for these results.", "contents": "Intermediate states of actomyosin adenosine triphosphatase. The early kinetic steps of actomyosin subfragment 1 (acto-S1) adenosine triphosphatase have been investigated by simultaneous monitoring of fluorescence and light scattering and also by observation of the time course of the production of phosphate. The results show that fluorescence enhancement occurs after the dissociation of actomyosin and that the rate of enhancement is similar to the maximum rate of enhancement for S1 alone, under similar conditions of pH and temperature. The maximum rate of the phosphate burst for acto S1 is also approximately the same as that for S1 alone. The maximum rates for fluorescence enhancement or phosphate formation are reached at much lower adenosine triphosphate concentrations for acto-S1 than for S1. An extension of the actomyosin scheme is presented which accounts for these results."}
{"id": "PMID:12793", "title": "Energetics and mechanism of actomyosin adenosine triphosphatase.", "content": "Rate constants were determined for the reaction of actin with subfragment 1 (S1), S1-product complex, heavy  meromyosin (HMM), and HMM-products complex for a range of temperatures, pH's, and ionic strengths. For actin concentrations up to 10 muM, the rate of reassociation of the product intermediate was equal to the rate of actomyosin subfragment 1 (acto-S1) or acto-HMM adenosine triphosphatase (ATPase). Therefore, under these conditions, the only  important pathway for adenosine triphosphate hydrolysis is through the dissociation and recombination of S1 or HMM. The apparent rate constants for the association of S1 and S1-product with actin showed a similar large ionic strength dependence. The S1-product reaction had a large temperature dependence paralleling the rate of acto-S1 ATPase, while the reaction with S1 had a much smaller variation with temperature. The low value of the rate constant for the S1-product reaction and its relationship to the s1 areaction suggests that the apparent rate constant does not measure a simple second-order reaction. A plausible mechanism is a rapid equilibrium for the binding step, followed by a transition (product release) which  increases the association constant. A refractory state could also reduce the apparent rate constant of recombination. An approximate assignment of equilibrium constants for the acto-S1 ATPase reaction was made based on the interpretation of the present evidence and equilibrium constnats for the S1 ATPase.", "contents": "Energetics and mechanism of actomyosin adenosine triphosphatase. Rate constants were determined for the reaction of actin with subfragment 1 (S1), S1-product complex, heavy  meromyosin (HMM), and HMM-products complex for a range of temperatures, pH's, and ionic strengths. For actin concentrations up to 10 muM, the rate of reassociation of the product intermediate was equal to the rate of actomyosin subfragment 1 (acto-S1) or acto-HMM adenosine triphosphatase (ATPase). Therefore, under these conditions, the only  important pathway for adenosine triphosphate hydrolysis is through the dissociation and recombination of S1 or HMM. The apparent rate constants for the association of S1 and S1-product with actin showed a similar large ionic strength dependence. The S1-product reaction had a large temperature dependence paralleling the rate of acto-S1 ATPase, while the reaction with S1 had a much smaller variation with temperature. The low value of the rate constant for the S1-product reaction and its relationship to the s1 areaction suggests that the apparent rate constant does not measure a simple second-order reaction. A plausible mechanism is a rapid equilibrium for the binding step, followed by a transition (product release) which  increases the association constant. A refractory state could also reduce the apparent rate constant of recombination. An approximate assignment of equilibrium constants for the acto-S1 ATPase reaction was made based on the interpretation of the present evidence and equilibrium constnats for the S1 ATPase."}
{"id": "PMID:12794", "title": "Relaxation spectra of yeast hexokinases. Isomerization of the enzyme.", "content": "Yeast hexokinase isozymes P1 and P11 exhibit a pH dependent, rapid relaxation process at 15 degrees C at enzyme concentrations of 100-474 muM and over a pH range of 6-8. The process was detected by equilibrium temperature jump spectroscopy using the indicator probe phenol red. The value of 1/tau varies from about 6 ms-1 at pH 8 for both isozymes to 50 ms-1 for P1 and 85 ms-1 for P11 at pH 6. The data are consistent with a mechanism involving an enzyme isomerization coupled to an ionization. The forward rate constant for the isomerization of the proposed mechanism varies between 3 and 7 ms-1; the ratio of the reverse rate constant to the ionization Ka is between 0.5 and 2 X 10(11) M-1 S-1; the estimated pKa varies between 5.5 and 6.1. The ranges of values in rate constants and pKa represent variations observed between preparations of the same isozyme and between isozymes. The isomerization rate is at least 50 times faster than catalysis under all conditions and the pKa is lower than that controlling activity. The rate of isomerization is unchanged by addition of sugar and nucleotide ligands, but the amplitude of the process is perturbed. These data imply that isomerizing and ionizing forms are sensitive to events at the active site. These equilibria between forms of hexokinase are fast enough, and have the right properties, to be important to the mechanism and regulation of the enzyme.", "contents": "Relaxation spectra of yeast hexokinases. Isomerization of the enzyme. Yeast hexokinase isozymes P1 and P11 exhibit a pH dependent, rapid relaxation process at 15 degrees C at enzyme concentrations of 100-474 muM and over a pH range of 6-8. The process was detected by equilibrium temperature jump spectroscopy using the indicator probe phenol red. The value of 1/tau varies from about 6 ms-1 at pH 8 for both isozymes to 50 ms-1 for P1 and 85 ms-1 for P11 at pH 6. The data are consistent with a mechanism involving an enzyme isomerization coupled to an ionization. The forward rate constant for the isomerization of the proposed mechanism varies between 3 and 7 ms-1; the ratio of the reverse rate constant to the ionization Ka is between 0.5 and 2 X 10(11) M-1 S-1; the estimated pKa varies between 5.5 and 6.1. The ranges of values in rate constants and pKa represent variations observed between preparations of the same isozyme and between isozymes. The isomerization rate is at least 50 times faster than catalysis under all conditions and the pKa is lower than that controlling activity. The rate of isomerization is unchanged by addition of sugar and nucleotide ligands, but the amplitude of the process is perturbed. These data imply that isomerizing and ionizing forms are sensitive to events at the active site. These equilibria between forms of hexokinase are fast enough, and have the right properties, to be important to the mechanism and regulation of the enzyme."}
{"id": "PMID:12795", "title": "Effect of alcohols on the structure and function of D-amino-acid oxidase.", "content": "The absorption spectrum of D-amino-acid oxidase (D-amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3) was significantly perturbed by various alcohols; typical fine structures were observed in the visible absorption bands, accompanied by blue shifts of the peaks. Both fluorescence intensity and fluorescence polarization were increased upon the addition of alcohols, indicating that the coenzyme is not liberated from the apoenzyme but the hydrophobicity of the environment of the enzyme-bound flavin is increased. Upon the addition of alcohols, the circular dichroism of the enzyme was markedly modified in the visible and near-ultraviolet regions, while that of the apoenzyme in the near- and far-ultraviolet regions was scarcely modified, indicating a change in the interaction between the flavin coenzyme and protein. Both the apparent maximal velocity and the apparent Michaelis constant of the enzyme were increased by the addition of alcohols. The presence of alcohols tends to dissociate the dimer of this enzyme into the monomer, but the dissociation does not fully explain the increase in the maximal velocity of the enzyme by alcohols, because the increase in the maximal velocity caused by alcohols is larger than that expected from the dissociation. Since the rate of formation of the purple intermediate was decreased by alcohols in both the dimer and the monomer, the increase in the maximal velocity could be ascribed to an increase in the rate of dissociation of the enzyme-product complex. This increase could be ascribed to the protein conformational change, which is probably provoked by combination of alcohols with the enzyme at a locus other than that for substrate binding.", "contents": "Effect of alcohols on the structure and function of D-amino-acid oxidase. The absorption spectrum of D-amino-acid oxidase (D-amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3) was significantly perturbed by various alcohols; typical fine structures were observed in the visible absorption bands, accompanied by blue shifts of the peaks. Both fluorescence intensity and fluorescence polarization were increased upon the addition of alcohols, indicating that the coenzyme is not liberated from the apoenzyme but the hydrophobicity of the environment of the enzyme-bound flavin is increased. Upon the addition of alcohols, the circular dichroism of the enzyme was markedly modified in the visible and near-ultraviolet regions, while that of the apoenzyme in the near- and far-ultraviolet regions was scarcely modified, indicating a change in the interaction between the flavin coenzyme and protein. Both the apparent maximal velocity and the apparent Michaelis constant of the enzyme were increased by the addition of alcohols. The presence of alcohols tends to dissociate the dimer of this enzyme into the monomer, but the dissociation does not fully explain the increase in the maximal velocity of the enzyme by alcohols, because the increase in the maximal velocity caused by alcohols is larger than that expected from the dissociation. Since the rate of formation of the purple intermediate was decreased by alcohols in both the dimer and the monomer, the increase in the maximal velocity could be ascribed to an increase in the rate of dissociation of the enzyme-product complex. This increase could be ascribed to the protein conformational change, which is probably provoked by combination of alcohols with the enzyme at a locus other than that for substrate binding."}
{"id": "PMID:12796", "title": "S-adenosylmethionine: protein-arginine methyltransferase. Purification and mechanism of the enzyme.", "content": "Protein methylase I (S-adenosylmethionine: protein-arginine methyltransferase, EC 2.1.1.23) has been purified from calf brain approximately 120-fold with a 14% yield. The final preparation is completely free of any other protein-specific methyltransferases and endogenous substrate protein. The enzyme has an optimum pH of 7.2 and pI value of 5.1. The Km values for S-adenosyl-L-methionine, histone H4, and an ancephalitogenic basic protein are 7.6 X 10(-6), 2.5 X 10(-5), and 7.1 X 10(-5) M, respectively, and the Ki value for S-adenosyl-L-homocysteine is 2.62 X 10(-6) M. The enzyme is highly specific for the arginine residues of protein, and the end products after hydrolysis of the methylated protein are NG,NG-di(asymmetric), NG,N'G-di(symmetric), and NG-monomethylarginine. The ratio of [14C]methyl incorporation into these derivatives by enzyme preparation at varying stages of purification remains unchanged at 40:5:55, strongly indicating that a single enzyme is involved in the synthesis of the three arginine derivatives. The kinetic mechanism of the protein methylase I reaction was studied with the purified enzyme. Initial velocity patterns converging at a point on the extended axis of abscissas were obtained with either histone H4 or S-adenosyl-L-methionine as the varied substrate. Product inhibition by S-adenosyl-L-homocysteine with S-adenosyl-L-methionine as the varied substrate was competitive regardless of whether or not the enzyme was saturated with histone H4. On the other hand, when histone H4 is the variable substrate, noncompetitive inhibition was obtained with S-adenosyl-L-homocysteine under conditions where the enzyme is not saturated with the other substrate, S-adenosyl-L-methionine. These results suggest that the mechanism of the protein methylase I reaction is a Sequential Ordered Bi Bi mechanism with S-adenosyl-L-methionine as the first substrate, histone H4 as the second substrate, methylated histone H4 as the first product, and S-adenosyl-L-homocysteine as the second product released.", "contents": "S-adenosylmethionine: protein-arginine methyltransferase. Purification and mechanism of the enzyme. Protein methylase I (S-adenosylmethionine: protein-arginine methyltransferase, EC 2.1.1.23) has been purified from calf brain approximately 120-fold with a 14% yield. The final preparation is completely free of any other protein-specific methyltransferases and endogenous substrate protein. The enzyme has an optimum pH of 7.2 and pI value of 5.1. The Km values for S-adenosyl-L-methionine, histone H4, and an ancephalitogenic basic protein are 7.6 X 10(-6), 2.5 X 10(-5), and 7.1 X 10(-5) M, respectively, and the Ki value for S-adenosyl-L-homocysteine is 2.62 X 10(-6) M. The enzyme is highly specific for the arginine residues of protein, and the end products after hydrolysis of the methylated protein are NG,NG-di(asymmetric), NG,N'G-di(symmetric), and NG-monomethylarginine. The ratio of [14C]methyl incorporation into these derivatives by enzyme preparation at varying stages of purification remains unchanged at 40:5:55, strongly indicating that a single enzyme is involved in the synthesis of the three arginine derivatives. The kinetic mechanism of the protein methylase I reaction was studied with the purified enzyme. Initial velocity patterns converging at a point on the extended axis of abscissas were obtained with either histone H4 or S-adenosyl-L-methionine as the varied substrate. Product inhibition by S-adenosyl-L-homocysteine with S-adenosyl-L-methionine as the varied substrate was competitive regardless of whether or not the enzyme was saturated with histone H4. On the other hand, when histone H4 is the variable substrate, noncompetitive inhibition was obtained with S-adenosyl-L-homocysteine under conditions where the enzyme is not saturated with the other substrate, S-adenosyl-L-methionine. These results suggest that the mechanism of the protein methylase I reaction is a Sequential Ordered Bi Bi mechanism with S-adenosyl-L-methionine as the first substrate, histone H4 as the second substrate, methylated histone H4 as the first product, and S-adenosyl-L-homocysteine as the second product released."}
{"id": "PMID:12797", "title": "Purification and properties of Renilla reniformis luciferase.", "content": "Luciferase from the anthozoan coelenterate Renilla reniformis (Renilla luciferin:oxygen 2-oxidoreductase (decarboxylating), EC 1.13.12.5.) catalyzes the bioluminescent oxidation of Renilla luciferin producing light (lambdaB 480 nm, QB 5.5%), oxyluciferin, and CO2 (Hori, K., Wampler, J.E., Matthews, J.C., and Cormier, M.J. (1973), Biochemistry 12, 4463). Using a combination of ion-exchange, molecular-sieve, sulfhydryl-exchange, and affinity chromatography, luciferase has been purified, approximately 12 000-fold with 24% recovery, to homogeneity as judged by analysis with disc and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and ultracentrifugation. Renilla luciferase is active as a nearly spherical single polypeptide chain monomer of 3.5 X 10(4) daltons having a specific activity of 1.8 X 10(15) hp s-1 mg-1 and a turnover number of 111 mumol min-1 mumol-1 of enzyme. This enzyme has a high content of aromatic and hydrophobic amino acids such that it has an epsilon280nm 0.1% of 2.1 and an average hydrophobicity of 1200 cal residue-1. The high average hydrophobicity of luciferase, which places it among the more hydrophobic proteins reported, is believed to account, at least in part, for its tendency to self-associate forming inactive dimers and higher molecular weight species.", "contents": "Purification and properties of Renilla reniformis luciferase. Luciferase from the anthozoan coelenterate Renilla reniformis (Renilla luciferin:oxygen 2-oxidoreductase (decarboxylating), EC 1.13.12.5.) catalyzes the bioluminescent oxidation of Renilla luciferin producing light (lambdaB 480 nm, QB 5.5%), oxyluciferin, and CO2 (Hori, K., Wampler, J.E., Matthews, J.C., and Cormier, M.J. (1973), Biochemistry 12, 4463). Using a combination of ion-exchange, molecular-sieve, sulfhydryl-exchange, and affinity chromatography, luciferase has been purified, approximately 12 000-fold with 24% recovery, to homogeneity as judged by analysis with disc and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and ultracentrifugation. Renilla luciferase is active as a nearly spherical single polypeptide chain monomer of 3.5 X 10(4) daltons having a specific activity of 1.8 X 10(15) hp s-1 mg-1 and a turnover number of 111 mumol min-1 mumol-1 of enzyme. This enzyme has a high content of aromatic and hydrophobic amino acids such that it has an epsilon280nm 0.1% of 2.1 and an average hydrophobicity of 1200 cal residue-1. The high average hydrophobicity of luciferase, which places it among the more hydrophobic proteins reported, is believed to account, at least in part, for its tendency to self-associate forming inactive dimers and higher molecular weight species."}
{"id": "PMID:12798", "title": "Oxidation of spermidine and spermine in rat liver: purification and properties of polyamine oxidase.", "content": "A novel enzyme responsible for the oxidation of spermidine and spermine has been found in rat liver. Spermidine is shown to be degraded to putrescine and 3-aminopropionaldehyde, and spermine to be cleaved to spermidine and 3-aminopropionaldehyde. A single enzyme catalyzing both reactions and designated as polyamine oxidase has been purified 4000-fold to electrophoretic homogeneity. Polyamine oxidase appears to be a flavoprotein, containing flavin adenine dinucleotide (FAD) as a prosthetic group. Hydrogen peroxide is evolved in the reaction and no other electron acceptors except molecular oxygen have been found. The molecular weight of the enzyme was approximately 60 000 and the sedimentation coefficient 4.5 S. The enzyme appears to be a single polypeptide chain since no evidence for structural subunits was obtained. Polyamine oxidase was sensitive to sulfhydryl and carbonyl group reagents. The optimum pH value for the oxidation of polyamines was close to 10. The reaction velocities were enhanced by various aldehydes, especially certain aromatic aldehydes. Polyamine oxidase appears to be localized in peroxisomes of liver cells, although the existence of an isoenzyme in the cytosolic fraction was not definitively ruled out. No marked changes were observed in the activity of polyamine oxidase in rat liver after partial hepatectomy, carbon tetrachloride poisoning, and after treatment with growth hormone or thioacetamide, conditions which are known to alter profoundly the metabolism and accumulation of polyamines.", "contents": "Oxidation of spermidine and spermine in rat liver: purification and properties of polyamine oxidase. A novel enzyme responsible for the oxidation of spermidine and spermine has been found in rat liver. Spermidine is shown to be degraded to putrescine and 3-aminopropionaldehyde, and spermine to be cleaved to spermidine and 3-aminopropionaldehyde. A single enzyme catalyzing both reactions and designated as polyamine oxidase has been purified 4000-fold to electrophoretic homogeneity. Polyamine oxidase appears to be a flavoprotein, containing flavin adenine dinucleotide (FAD) as a prosthetic group. Hydrogen peroxide is evolved in the reaction and no other electron acceptors except molecular oxygen have been found. The molecular weight of the enzyme was approximately 60 000 and the sedimentation coefficient 4.5 S. The enzyme appears to be a single polypeptide chain since no evidence for structural subunits was obtained. Polyamine oxidase was sensitive to sulfhydryl and carbonyl group reagents. The optimum pH value for the oxidation of polyamines was close to 10. The reaction velocities were enhanced by various aldehydes, especially certain aromatic aldehydes. Polyamine oxidase appears to be localized in peroxisomes of liver cells, although the existence of an isoenzyme in the cytosolic fraction was not definitively ruled out. No marked changes were observed in the activity of polyamine oxidase in rat liver after partial hepatectomy, carbon tetrachloride poisoning, and after treatment with growth hormone or thioacetamide, conditions which are known to alter profoundly the metabolism and accumulation of polyamines."}
{"id": "PMID:12799", "title": "Hydrolysis of chyle cholesterol esters with cell-free preparations of rat liver.", "content": "1. The effect of pH on the hydrolysis of chylomicron and chylomicron remnant cholesterol ester with rat liver homogenate was examined. The hydrolysis had three pH optima, at pH 4.5, at pH 6.0-6.5 and at pH 8.5. At the two upper pH optima extensive cholesterol ester hydrolysis occurred without simultaneous degradation of the triacylglycerol portion. 2. Similarly, microsomes (at pH 6.5-8.0) and 100 000 X g supernatant (at pH 7.5-8.5) efficiently hydrolyzed the cholesterol ester but not the triacylglycerol of chylomicron remnants. 3. With the same substrate no enrichment of neutral cholesterol esterase activity was seen in isolated plasma membranes. 4. At pH 4.5 lysosomes efficiently hydrolyzed both the cholesterol ester and the triacylglycerol portion of chylomicron remnants. 5. Three conclusions are drawn: (a) the study provides evidence against the existence of a plasma membrane-bound enzyme-hydrolyzing chylomicron cholesterol ester before or during its penetration into the cell; (b) enzymes of the cell sap and possibly of the endoplasmic reticulum can degrade cholesterol ester of chylomicron remnants without preceeding hydrolysis of the triacylglycerol core; and (c) lysosomal enzymes can degrade both the cholesterol ester and the triacylglycerol portion of chylomicron remnants if these are taken up as whole particles by endocytosis.", "contents": "Hydrolysis of chyle cholesterol esters with cell-free preparations of rat liver. 1. The effect of pH on the hydrolysis of chylomicron and chylomicron remnant cholesterol ester with rat liver homogenate was examined. The hydrolysis had three pH optima, at pH 4.5, at pH 6.0-6.5 and at pH 8.5. At the two upper pH optima extensive cholesterol ester hydrolysis occurred without simultaneous degradation of the triacylglycerol portion. 2. Similarly, microsomes (at pH 6.5-8.0) and 100 000 X g supernatant (at pH 7.5-8.5) efficiently hydrolyzed the cholesterol ester but not the triacylglycerol of chylomicron remnants. 3. With the same substrate no enrichment of neutral cholesterol esterase activity was seen in isolated plasma membranes. 4. At pH 4.5 lysosomes efficiently hydrolyzed both the cholesterol ester and the triacylglycerol portion of chylomicron remnants. 5. Three conclusions are drawn: (a) the study provides evidence against the existence of a plasma membrane-bound enzyme-hydrolyzing chylomicron cholesterol ester before or during its penetration into the cell; (b) enzymes of the cell sap and possibly of the endoplasmic reticulum can degrade cholesterol ester of chylomicron remnants without preceeding hydrolysis of the triacylglycerol core; and (c) lysosomal enzymes can degrade both the cholesterol ester and the triacylglycerol portion of chylomicron remnants if these are taken up as whole particles by endocytosis."}
{"id": "PMID:12800", "title": "Characterization of the acetyl-CoA synthetase of Acetobacter aceti.", "content": "The acetate activating system of Acetobacter aceti has been studied. The enzyme responsible, acetyl-CoA synthetase, has been purified about 500-fold from crude cell extracts and was approximately 85% pure as judged by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The purified enzyme showed optimal activity at pH 7.6 in both Tris-HCL and potassium phosphate buffers. In its purest form, the enzyme was stable at 4 degrees-C but denatured upon freezing. The Km values for CoA, ATP and acetate were found to be 0.104 mM, 0.36 mM and 0.25 mM respectively; propionate and acrylate were also activated by the enzyme but not butyrate, isobutyrate or valerate. GTP, UTP, CTP and ADP could not replace ATP in the reaction, and cysteine or pantetheine failed to replace CoA. The cationic requirements were studied and of the divalent cations tested, only Mn2+ could significantly replace Mg2+ in the reaction; K+ and NH4+ stimulated enzyme activity but inhibited at high concentrations; Na+ was a poor activator, but did not inhibit at higher concentrations. The effect of a number of glucose and other metabolites on enzyme activity has been tested.", "contents": "Characterization of the acetyl-CoA synthetase of Acetobacter aceti. The acetate activating system of Acetobacter aceti has been studied. The enzyme responsible, acetyl-CoA synthetase, has been purified about 500-fold from crude cell extracts and was approximately 85% pure as judged by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The purified enzyme showed optimal activity at pH 7.6 in both Tris-HCL and potassium phosphate buffers. In its purest form, the enzyme was stable at 4 degrees-C but denatured upon freezing. The Km values for CoA, ATP and acetate were found to be 0.104 mM, 0.36 mM and 0.25 mM respectively; propionate and acrylate were also activated by the enzyme but not butyrate, isobutyrate or valerate. GTP, UTP, CTP and ADP could not replace ATP in the reaction, and cysteine or pantetheine failed to replace CoA. The cationic requirements were studied and of the divalent cations tested, only Mn2+ could significantly replace Mg2+ in the reaction; K+ and NH4+ stimulated enzyme activity but inhibited at high concentrations; Na+ was a poor activator, but did not inhibit at higher concentrations. The effect of a number of glucose and other metabolites on enzyme activity has been tested."}
{"id": "PMID:12801", "title": "Stabilization of an acetyl-coenzyme A carboxylase complex from Pseudomonas citronellolis.", "content": "Using stabilizing conditions the acetyl-CoA carboxylase (EC 6.4.1.2) of Pseudomonas citronellolis has been isolated as a complex containing four different polypeptide chains with molecular weights of 53 000, 36 000, 33 000 and 25 000. Evidence is presented to suggest that these polypeptide chains correspond to distinct biotin carboxylase, transcarboxylase and biotin carboxyl carrier protein subunits in analogy with similar subunits of Escherichia coli acetyl-CoA carboxylase, an unstable complex in vitro.", "contents": "Stabilization of an acetyl-coenzyme A carboxylase complex from Pseudomonas citronellolis. Using stabilizing conditions the acetyl-CoA carboxylase (EC 6.4.1.2) of Pseudomonas citronellolis has been isolated as a complex containing four different polypeptide chains with molecular weights of 53 000, 36 000, 33 000 and 25 000. Evidence is presented to suggest that these polypeptide chains correspond to distinct biotin carboxylase, transcarboxylase and biotin carboxyl carrier protein subunits in analogy with similar subunits of Escherichia coli acetyl-CoA carboxylase, an unstable complex in vitro."}
{"id": "PMID:12802", "title": "Effect of sodium fluoride on glucose-6-phosphate dehydrogenase activity in the rat uterus.", "content": "Intrauterine administration of 50 mumol of NaF to the ovariectomized mature rat causes a 2--3-fold increase in the total uterine glucose-6-phosphate dehydrogenase activity within 24 h. The response is characterized by a 4--6 h lag with a maximum effect from 24 to 36 h after a single treatment. Uterine glucose-6-phosphate dehydrogenase activity continues to increase with daily administration of NaF through 4 days. The NaF-induced response is blocked by prior intrauterine administration of cycloheximide but not actinomycin D suggesting that the enzyme activity increases by a post-transcriptional effect of NaF on de novo enzyme synthesis. Direct measurement of the effect of NaF on the rate of incorporation of [14C] leucine into immunoprecipitable uterine glucose-6-phosphate dehydrogenase indicates that NaF causes a 9-fold increase in the rate of enzyme synthesis during the interval from 12 to 16 h after treatment. The half-life of the enzyme as measured by the rate of loss of [1-14C] glutamate from previously labeled utreine glucose-6-phosphate dehydrogenase is decreased  from 27 to 10 h by NaF. The NaF response does not seem to be mediated by activation of uterine adenylyl cyclase since theophylline does not potentiate the response and since intrauterine application of cyclic AMP does not mimic the response. The increase in enzyme activity is preceded by an increase in the rate of utilization of the hexose monophosphate shunt pathway as determined by the ratio of the the rates of oxidation of [1-14C]glucose to [6-14C] glucose to CO2 by uterine slices in vitro. The action of NaF on this pathway most likely resutls from inhibition of the glycolytic enzyme, enolase, and increased pathway utilization may be the factor which controls enzyme synthesis. When given in combination with other known inducers of uterine glucose-6-phosphate dehydrogenase such as estradiol and NADP+, NaF acts synergistically.", "contents": "Effect of sodium fluoride on glucose-6-phosphate dehydrogenase activity in the rat uterus. Intrauterine administration of 50 mumol of NaF to the ovariectomized mature rat causes a 2--3-fold increase in the total uterine glucose-6-phosphate dehydrogenase activity within 24 h. The response is characterized by a 4--6 h lag with a maximum effect from 24 to 36 h after a single treatment. Uterine glucose-6-phosphate dehydrogenase activity continues to increase with daily administration of NaF through 4 days. The NaF-induced response is blocked by prior intrauterine administration of cycloheximide but not actinomycin D suggesting that the enzyme activity increases by a post-transcriptional effect of NaF on de novo enzyme synthesis. Direct measurement of the effect of NaF on the rate of incorporation of [14C] leucine into immunoprecipitable uterine glucose-6-phosphate dehydrogenase indicates that NaF causes a 9-fold increase in the rate of enzyme synthesis during the interval from 12 to 16 h after treatment. The half-life of the enzyme as measured by the rate of loss of [1-14C] glutamate from previously labeled utreine glucose-6-phosphate dehydrogenase is decreased  from 27 to 10 h by NaF. The NaF response does not seem to be mediated by activation of uterine adenylyl cyclase since theophylline does not potentiate the response and since intrauterine application of cyclic AMP does not mimic the response. The increase in enzyme activity is preceded by an increase in the rate of utilization of the hexose monophosphate shunt pathway as determined by the ratio of the the rates of oxidation of [1-14C]glucose to [6-14C] glucose to CO2 by uterine slices in vitro. The action of NaF on this pathway most likely resutls from inhibition of the glycolytic enzyme, enolase, and increased pathway utilization may be the factor which controls enzyme synthesis. When given in combination with other known inducers of uterine glucose-6-phosphate dehydrogenase such as estradiol and NADP+, NaF acts synergistically."}
{"id": "PMID:12803", "title": "Acid inactivation of short-lived rat liver enzymes.", "content": "The stabilities of nine rat liver cytosol enzymes were compared at a variety of pH values. The cytosol enzymes studied were (a) those with half-lives in vivo of 3 days or longer: lactate dehydrogenase, arginase, glyceraldehyde phosphate dehydrogenase and alanine aminotransferase, (b) those with half-lives in vivo shorter than 2 days; glucokinase, dihydroorotase, serine dehydratase and tyrosine aminotransferase and (c) catalase, which has an intermediate half-life of 2.5 days for the protein protion. All the enzymes were stable in vitro at neurtal and alkaline pH values. However, at acidic pH values (pH 4): the long-lived enzymes (a) were stable; the short-lived enzymes (b) were completely inactivated with one exception; and catalase was partially inactivated. Tyrosine aminotransferase was the exception in that it is a short-lived enzyme in vivo but  stable under all conditions tested in vitro. The finding that long-lived enzymes are stable in an acid milieu and short-lived enzymes are generally unstable was only observed if certain ligands (NAD+, pyridoxal 5'-phosphate, Mn2+, amino acids) were added to the invitro system. Lysosomal extracts did not accelerate the rate of inactivation of any cytosol enzyme in acidic solutions. These results indicate that if degradation of intracellular enzymes occurs in lysosomes, acid inactivation and denaturation of enzymes may be the initial event in determining the functional half-lives of the enzymes in vivo.", "contents": "Acid inactivation of short-lived rat liver enzymes. The stabilities of nine rat liver cytosol enzymes were compared at a variety of pH values. The cytosol enzymes studied were (a) those with half-lives in vivo of 3 days or longer: lactate dehydrogenase, arginase, glyceraldehyde phosphate dehydrogenase and alanine aminotransferase, (b) those with half-lives in vivo shorter than 2 days; glucokinase, dihydroorotase, serine dehydratase and tyrosine aminotransferase and (c) catalase, which has an intermediate half-life of 2.5 days for the protein protion. All the enzymes were stable in vitro at neurtal and alkaline pH values. However, at acidic pH values (pH 4): the long-lived enzymes (a) were stable; the short-lived enzymes (b) were completely inactivated with one exception; and catalase was partially inactivated. Tyrosine aminotransferase was the exception in that it is a short-lived enzyme in vivo but  stable under all conditions tested in vitro. The finding that long-lived enzymes are stable in an acid milieu and short-lived enzymes are generally unstable was only observed if certain ligands (NAD+, pyridoxal 5'-phosphate, Mn2+, amino acids) were added to the invitro system. Lysosomal extracts did not accelerate the rate of inactivation of any cytosol enzyme in acidic solutions. These results indicate that if degradation of intracellular enzymes occurs in lysosomes, acid inactivation and denaturation of enzymes may be the initial event in determining the functional half-lives of the enzymes in vivo."}
{"id": "PMID:12804", "title": "Thermoplasma acidophilum: intracellular pH and potassium concentration.", "content": "Thermoplasma acidophilum is a free-living thermophilic mycoplasma. Although the organism lacks a cell wall, it can grow in medium as dilute as 66 mosM. The intracellular K+ concentration can be as low as 17 mM, but varies according to the osmolality of the culture medium. The internal pH can be measured by taking advantage of the fact that T. acidophilum undergoes lysis when the pH is adjusted to neutrality. Thus, by appropriate analysis of titration curves, it is possible to conclude that the internal pH is near 5.5. This result was confirmed by a second type of experiment in which the internal pH was analyzed by rupturing the cells in a French Pressure Cell.", "contents": "Thermoplasma acidophilum: intracellular pH and potassium concentration. Thermoplasma acidophilum is a free-living thermophilic mycoplasma. Although the organism lacks a cell wall, it can grow in medium as dilute as 66 mosM. The intracellular K+ concentration can be as low as 17 mM, but varies according to the osmolality of the culture medium. The internal pH can be measured by taking advantage of the fact that T. acidophilum undergoes lysis when the pH is adjusted to neutrality. Thus, by appropriate analysis of titration curves, it is possible to conclude that the internal pH is near 5.5. This result was confirmed by a second type of experiment in which the internal pH was analyzed by rupturing the cells in a French Pressure Cell."}
{"id": "PMID:12805", "title": "Mechanism of the inhibitory effect of glyoxylate plus oxaloacetate and oxalomalate on the NADP-specific isocitrate dehydrogenase.", "content": "The effects of glyoxylate plus oxaloacetate and of oxalomalate on the NADP-linked isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating, EC 1.1.1.42) from pig heart from been studied with steady state methods as well as with stopped flow technique. When equimolar mixtures of glyoxylate and oxaloacetate were premixed for different lengths of time prior to addition to the assay mixture, the extent of inhibition increased with the premixing time. The results indicated that the inhibition by glyoxylate plus oxaloacetate is caused by a compound formed in a reversible interaction between the two components. Glyoxylate plus oxaloacetate and oxalomalate affected the enzyme in at least three different ways. They inhibited the enzyme in a reaction competitive with regard to the substrate isocitrate. This inhibition needed a certain time to be fully expressed. The time lag could be eliminated by premixing of the enzyme and inhibitor with NADP plus metal ion. Secondly, if the enzyme is premixed with NADP plus metal ions, a time lag occurs before the reaction rate approaches a constant value after initiation of the reaction with isocitrate. The inhibitors were found to enhance this effect of NADP plus metal ions on the enzyme. Thirdly, it has previously been shown that the enzyme can be activated by metal complexing agents. Glyoxylate plus oxaloacetate as well as oxalomalate are able to form complexes with metal ions and were found to cause an initial activation of the enzyme under certain assay conditions. The controversy regarding the mechanism of action of the above inhibitors on the enzyme is probably due to the fact that they affect the enzyme in several different ways.", "contents": "Mechanism of the inhibitory effect of glyoxylate plus oxaloacetate and oxalomalate on the NADP-specific isocitrate dehydrogenase. The effects of glyoxylate plus oxaloacetate and of oxalomalate on the NADP-linked isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating, EC 1.1.1.42) from pig heart from been studied with steady state methods as well as with stopped flow technique. When equimolar mixtures of glyoxylate and oxaloacetate were premixed for different lengths of time prior to addition to the assay mixture, the extent of inhibition increased with the premixing time. The results indicated that the inhibition by glyoxylate plus oxaloacetate is caused by a compound formed in a reversible interaction between the two components. Glyoxylate plus oxaloacetate and oxalomalate affected the enzyme in at least three different ways. They inhibited the enzyme in a reaction competitive with regard to the substrate isocitrate. This inhibition needed a certain time to be fully expressed. The time lag could be eliminated by premixing of the enzyme and inhibitor with NADP plus metal ion. Secondly, if the enzyme is premixed with NADP plus metal ions, a time lag occurs before the reaction rate approaches a constant value after initiation of the reaction with isocitrate. The inhibitors were found to enhance this effect of NADP plus metal ions on the enzyme. Thirdly, it has previously been shown that the enzyme can be activated by metal complexing agents. Glyoxylate plus oxaloacetate as well as oxalomalate are able to form complexes with metal ions and were found to cause an initial activation of the enzyme under certain assay conditions. The controversy regarding the mechanism of action of the above inhibitors on the enzyme is probably due to the fact that they affect the enzyme in several different ways."}
{"id": "PMID:12806", "title": "Determination of the redox potential of deazariboflavin by equilibration with flavins.", "content": "The redox potential of deazariboflavin has been determined for pH values from 5.5 to 9.2 by equilibration with riboflavin and lumiflavin 3-acetate. The position of the equilibrium with riboflavin was measured spectrophotometrically and fluorimetrically; the equilibrium potential with lumiflavin 3-acetate was measured spectrophotometrically and potentiometrically. The Em7 for deazariboflavin was found to be--0.273 +/- 0.003 V against the standard hydrogen electrode. Equilibrium with flavodoxin at pH 9.5 and 10.0 was also used to determine the redox potential of deazariboflavin at high pH values. The pK of dihydrodeazariboflavin was found from the break in the potential vs. pH diagram and from spectrophotometric pH titration. The pK value obtained by both methods is 7.00 +/- 0.05. We found that borate, a product of the reducing agent borohydride, complexed with the ribityl sidechain of deazariboflavin, causing a shift in the pK for the reduced form to values of about 8.", "contents": "Determination of the redox potential of deazariboflavin by equilibration with flavins. The redox potential of deazariboflavin has been determined for pH values from 5.5 to 9.2 by equilibration with riboflavin and lumiflavin 3-acetate. The position of the equilibrium with riboflavin was measured spectrophotometrically and fluorimetrically; the equilibrium potential with lumiflavin 3-acetate was measured spectrophotometrically and potentiometrically. The Em7 for deazariboflavin was found to be--0.273 +/- 0.003 V against the standard hydrogen electrode. Equilibrium with flavodoxin at pH 9.5 and 10.0 was also used to determine the redox potential of deazariboflavin at high pH values. The pK of dihydrodeazariboflavin was found from the break in the potential vs. pH diagram and from spectrophotometric pH titration. The pK value obtained by both methods is 7.00 +/- 0.05. We found that borate, a product of the reducing agent borohydride, complexed with the ribityl sidechain of deazariboflavin, causing a shift in the pK for the reduced form to values of about 8."}
{"id": "PMID:12807", "title": "Isolation, purification and characterization of bovine epidermal transglutaminase.", "content": "A crosslinking enzyme, epidermal transglutaminase, was isolated from soluble proteins of glabrous cow snout epidermis. This enzyme stabilized fibrin clots rendering them insoluble in 2% acetic acid. It also catalyzed the incorporation of the fluorescent amine, dansyl cadaverine, into casein. Epidermal transglutaminase was purified by chromatography upon DEAE-Sephadex A-50, zone electrophoresis in Pevikon, and Sephadex G-200 gel permeation chromatography. The highly purified substance, which had a specific activity of 3267 amine-incorporating units/mg per h and a molecular weight of 55000, behaved as a single molecular species in the analytical ultracentrifuge. It had a sedimentation coefficient of 4.4 S and migrated as a gamma-globulin at pH 8.6; it displayed anomalous migration in polyacrylamide gels containing sodium dodecyl sulfate. The enzyme was dependent upon free calcium ions and a reduced sulfhydryl group for activity. The apparent Km for dansyl cadaverine was 1.2 - 10(-4) at pH 7.5. Monospecific antiserum to bovine epidermal transglutaminase precipitated with the enzyme in agar. The antiserum prevented fibrin crosslinking but enhanced incorporation of dansyl cadaverine into casein by the enzyme. The epidermal enzyme differed biochemically and immunochemically from bovine plasma transglutaminase (Factor XIII).", "contents": "Isolation, purification and characterization of bovine epidermal transglutaminase. A crosslinking enzyme, epidermal transglutaminase, was isolated from soluble proteins of glabrous cow snout epidermis. This enzyme stabilized fibrin clots rendering them insoluble in 2% acetic acid. It also catalyzed the incorporation of the fluorescent amine, dansyl cadaverine, into casein. Epidermal transglutaminase was purified by chromatography upon DEAE-Sephadex A-50, zone electrophoresis in Pevikon, and Sephadex G-200 gel permeation chromatography. The highly purified substance, which had a specific activity of 3267 amine-incorporating units/mg per h and a molecular weight of 55000, behaved as a single molecular species in the analytical ultracentrifuge. It had a sedimentation coefficient of 4.4 S and migrated as a gamma-globulin at pH 8.6; it displayed anomalous migration in polyacrylamide gels containing sodium dodecyl sulfate. The enzyme was dependent upon free calcium ions and a reduced sulfhydryl group for activity. The apparent Km for dansyl cadaverine was 1.2 - 10(-4) at pH 7.5. Monospecific antiserum to bovine epidermal transglutaminase precipitated with the enzyme in agar. The antiserum prevented fibrin crosslinking but enhanced incorporation of dansyl cadaverine into casein by the enzyme. The epidermal enzyme differed biochemically and immunochemically from bovine plasma transglutaminase (Factor XIII)."}
{"id": "PMID:12808", "title": "Molecular heterogeneity of rabbit heart phosphorylase kinase.", "content": "Phosphorylase kinase (ATP: phosphorylase-b phosphotransferase, EC 2.7.1.38) from rabbit heart, when submitted to electrophoresis on Pevikon, separates into two discrete peaks A and B. The two peaks have been analyzed using reelectrophoresis, chromatography on DEAE-cellulose, thermal stability, inactivation by EGTA (ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) and reaction with an anti-muscle phosphorylase kinase antiserum. It can be concluded that rabbit heart extracts contain two isozymes of phosphorylase kinase. The more negatively charged isozyme seems to be identical with the muscle enzyme. The other isozyme resembles the liver enzyme but differs from the major fraction of the latter by its charge. It is likely that there exist at least three molecular types of phosphorylase kinase.", "contents": "Molecular heterogeneity of rabbit heart phosphorylase kinase. Phosphorylase kinase (ATP: phosphorylase-b phosphotransferase, EC 2.7.1.38) from rabbit heart, when submitted to electrophoresis on Pevikon, separates into two discrete peaks A and B. The two peaks have been analyzed using reelectrophoresis, chromatography on DEAE-cellulose, thermal stability, inactivation by EGTA (ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) and reaction with an anti-muscle phosphorylase kinase antiserum. It can be concluded that rabbit heart extracts contain two isozymes of phosphorylase kinase. The more negatively charged isozyme seems to be identical with the muscle enzyme. The other isozyme resembles the liver enzyme but differs from the major fraction of the latter by its charge. It is likely that there exist at least three molecular types of phosphorylase kinase."}
{"id": "PMID:12809", "title": "External yeast beta-fructosidase. Affinity labeling of the active site.", "content": "Conduritol-B-epoxide, a compound structurally related to the substrates of external yeast beta-fructosidase (beta-D-fructofuranoside fructohydrolase, EC 3.2.1.26), is an active-site directed inhibitor of this enzyme. The inactivation is irreversible and first-order with respect to time and inhibitor concentration. From the kinetic data obtained, it is concluded that one molecule of inhibitor reacts with one molecule of the enzyme causing inactivation. The inactivation is prevented by the presence of substrates. The pH-dependence of inactivation shows two dissociating groups in the enzyme with pKa values 3.05 and 6.8 being involved in the inactivation process. A carboxylate at the active site with pKa 3.05 is suggested to be the reactive group with conduritol-B-epoxide.", "contents": "External yeast beta-fructosidase. Affinity labeling of the active site. Conduritol-B-epoxide, a compound structurally related to the substrates of external yeast beta-fructosidase (beta-D-fructofuranoside fructohydrolase, EC 3.2.1.26), is an active-site directed inhibitor of this enzyme. The inactivation is irreversible and first-order with respect to time and inhibitor concentration. From the kinetic data obtained, it is concluded that one molecule of inhibitor reacts with one molecule of the enzyme causing inactivation. The inactivation is prevented by the presence of substrates. The pH-dependence of inactivation shows two dissociating groups in the enzyme with pKa values 3.05 and 6.8 being involved in the inactivation process. A carboxylate at the active site with pKa 3.05 is suggested to be the reactive group with conduritol-B-epoxide."}
{"id": "PMID:12810", "title": "On the catalytic and binding sites of porcine enteropeptidase.", "content": "The active site of porcine enteropeptidase (EC 3.4.21.9) was investigated in order to characterize better both catalytic and binding sites. The participation of a serine and a histidine residue in the catalytic process was fully confirmed and the two residues were located on the light chain of the enzyme. The binding site was found to be composed of at least 2 subsites S1 and S2. The subsite S1 (similar to the trypsin-binding site) is responsible for the interactions with the small substrates of trypsin and the lysine side chain of trypsinogen, while subsite S2 (probably a cluster of lysines) is responsible for the interactions with the polyanionic sequence found in all trypsinogens. Binding of substrate by subsite S2 led to an increased efficiency of the catalytic site which can be correlated to the known high specificity of enteropeptidase.", "contents": "On the catalytic and binding sites of porcine enteropeptidase. The active site of porcine enteropeptidase (EC 3.4.21.9) was investigated in order to characterize better both catalytic and binding sites. The participation of a serine and a histidine residue in the catalytic process was fully confirmed and the two residues were located on the light chain of the enzyme. The binding site was found to be composed of at least 2 subsites S1 and S2. The subsite S1 (similar to the trypsin-binding site) is responsible for the interactions with the small substrates of trypsin and the lysine side chain of trypsinogen, while subsite S2 (probably a cluster of lysines) is responsible for the interactions with the polyanionic sequence found in all trypsinogens. Binding of substrate by subsite S2 led to an increased efficiency of the catalytic site which can be correlated to the known high specificity of enteropeptidase."}
{"id": "PMID:12811", "title": "On the specificity of bovine spleen cathepsin B2.", "content": "The specificity of bovine spleen cathepsin B2 has been investigated by means of some natural oligo- and polypeptides, i.e. glucagon, melittin, insulin A and B chain, bradykinin, angiotensin I and II, oxytocin ACTH, clupein and salmin. The enzyme is primarily a carboxypeptidase which hydrolyzes peptide linkages of most amino acids common to proteins. In addition, cathepsin B2 displays amidase and esterase activity without requiring a free carboxyl group. The main pH optimum is between 4 and 5, in some cases higher.", "contents": "On the specificity of bovine spleen cathepsin B2. The specificity of bovine spleen cathepsin B2 has been investigated by means of some natural oligo- and polypeptides, i.e. glucagon, melittin, insulin A and B chain, bradykinin, angiotensin I and II, oxytocin ACTH, clupein and salmin. The enzyme is primarily a carboxypeptidase which hydrolyzes peptide linkages of most amino acids common to proteins. In addition, cathepsin B2 displays amidase and esterase activity without requiring a free carboxyl group. The main pH optimum is between 4 and 5, in some cases higher."}
{"id": "PMID:12812", "title": "Activation of proenzyme of acidic protease from human seminal plasma.", "content": "The kinetics and the extent of the conversion of the proenzyme into the active acidic protease (EC 3.4.23.--) of human seminal plasma were dependent on acidic pH. Between pH 2 and 4, the initial rate of the activation was first-order with respect to the proenzyme. Between pH 4.5 and 5, the rate deviated from the first-order with an initial lag period which can be abolished by adding an excess amount of the acidic protease or pepsin. The extent of the activation was complete between pH 2 and 3 and became incomplete between pH 4 and 5. Addition of the acidic protease or pepsin did not alter the extent of the activation at the high pH values. According to the chromatographic profile on a Sephadex G-75 column, the activation products (namely active acidic protease and an activation peptide) obtained at pH 3 and those obtained at pH 4.5 were identical. The molecular weight of the activation peptide obtained at pH 3 was 6900; its amino acid composition was analyzed and compared with those of the proenzyme and the acidic protease. Remarkable similarity between the amino acid composition of the acidic protease and that of human pepsin was observed. In the presence of an excess amount of hemoglobin, the conversion of the proenzyme was self-activated and showed an initial lag period. Addition of acidic protease did not change the rate of self activation or the lag period.", "contents": "Activation of proenzyme of acidic protease from human seminal plasma. The kinetics and the extent of the conversion of the proenzyme into the active acidic protease (EC 3.4.23.--) of human seminal plasma were dependent on acidic pH. Between pH 2 and 4, the initial rate of the activation was first-order with respect to the proenzyme. Between pH 4.5 and 5, the rate deviated from the first-order with an initial lag period which can be abolished by adding an excess amount of the acidic protease or pepsin. The extent of the activation was complete between pH 2 and 3 and became incomplete between pH 4 and 5. Addition of the acidic protease or pepsin did not alter the extent of the activation at the high pH values. According to the chromatographic profile on a Sephadex G-75 column, the activation products (namely active acidic protease and an activation peptide) obtained at pH 3 and those obtained at pH 4.5 were identical. The molecular weight of the activation peptide obtained at pH 3 was 6900; its amino acid composition was analyzed and compared with those of the proenzyme and the acidic protease. Remarkable similarity between the amino acid composition of the acidic protease and that of human pepsin was observed. In the presence of an excess amount of hemoglobin, the conversion of the proenzyme was self-activated and showed an initial lag period. Addition of acidic protease did not change the rate of self activation or the lag period."}
{"id": "PMID:12813", "title": "Delayed fluorescence from bacteriochlorophyll in Chromatium vinosum chromatophores.", "content": "Delayed fluorescence from bacteriochlorophyll in Chromatium vinosum chromatophores was studied at room temperature and under intermittent illuminations. The decay of delayed fluorescence was constituted of two components; a fast component decayed with a half time of about 8 ms, a slow one decayed in parallel with the reduction of photooxidized bacteriochlorophyll (P+) with a half time of 100-200 ms. The biphasic decay of delayed fluorescence indicated that a rapid equilibrium was established between the primary electron acceptor and the secondary acceptor. In the presence of o-phenanthroline, the time course of the decay of delayed fluorescence was identical with that of the reduction  of P+ in reaction center-rich subchromatophore particles, although they did not necessarily coincide with each other in \"intact\" chromatophores. The intensity of the slow component was increased and the decay was accelerated at basic pH values. Reagents that dissipate the proton gradient across the chromatophore membranes such as carbonylcyanide m-chlorophenylhydrazone (CCCP) and nigericin accelerated the decay of the slow component. These effects are probably resulting from changes in internal pH of chromatophore vesicles. Reagents that dissipate the membrane potential such as CCCP and valinomycin decreased the intensity.", "contents": "Delayed fluorescence from bacteriochlorophyll in Chromatium vinosum chromatophores. Delayed fluorescence from bacteriochlorophyll in Chromatium vinosum chromatophores was studied at room temperature and under intermittent illuminations. The decay of delayed fluorescence was constituted of two components; a fast component decayed with a half time of about 8 ms, a slow one decayed in parallel with the reduction of photooxidized bacteriochlorophyll (P+) with a half time of 100-200 ms. The biphasic decay of delayed fluorescence indicated that a rapid equilibrium was established between the primary electron acceptor and the secondary acceptor. In the presence of o-phenanthroline, the time course of the decay of delayed fluorescence was identical with that of the reduction  of P+ in reaction center-rich subchromatophore particles, although they did not necessarily coincide with each other in \"intact\" chromatophores. The intensity of the slow component was increased and the decay was accelerated at basic pH values. Reagents that dissipate the proton gradient across the chromatophore membranes such as carbonylcyanide m-chlorophenylhydrazone (CCCP) and nigericin accelerated the decay of the slow component. These effects are probably resulting from changes in internal pH of chromatophore vesicles. Reagents that dissipate the membrane potential such as CCCP and valinomycin decreased the intensity."}
{"id": "PMID:12814", "title": "Proton electrochemical potential in steady state rat liver mitochondria.", "content": "Delta approximately muH has been determined in steady state mitochondria by measuring the magnitude of delta pH on the distribution of acetate and of deltapsi on the distribution of K+, tetraphenylphosphonium, Ca2+, Sr2+ and Mn2+. (1) The matrix concentration of divalent cations has been calculated from the total cation uptake, from the increase of matrix volume and from the ESR sextet signal of Mn(H2O)L2+. The [cat2+]i based on osmotic data is about five times higher than that based on ESR measurements. The [cat2+]i based on total uptake is much higher than that based on osmotic data at low cation/protein ratios. (2) In the presence of 10 mM acetate the maximal deltapsi on Ca2+ is about 130 mV and on Sr2+ is 95 mV. Deltapsi on Mn2+ is 91 or 109 mV, according to whether [cat2+-a)i is calculated from ESR or osmotic data. Under the same conditions, deltapH is about 60 mV. Hence delta approximately muH on divalent cations is between 151 and 190 mV. (3) Deltapsi on K+, in valinomycin treated mitochondria with 10 mM acetate or 2 mM Pi, drops from 200 mV, at low [K+]0 to almost zero parallel to the increase of [K+]0. DeltapH is 30 mV at low [K+]0 and about 42 mV at 600 muM K+. Hence delta approximately muH drops from 22m mV lower values with the increase of [K+]0. (4) Maximal deltapsi on triphenylmethylphosphonium is 140 mV. (5) When delta approximately muH is measured simultaneously on divalent cations and on K+, the values on K+ tend to approach those on Ca2+ while those on Sr2+ are about 50 mV lower. (6) It is concluded that the steady state mitochondrial energy potential is equivalent to a delta approximately muH between 150 and approx. 190 mV.", "contents": "Proton electrochemical potential in steady state rat liver mitochondria. Delta approximately muH has been determined in steady state mitochondria by measuring the magnitude of delta pH on the distribution of acetate and of deltapsi on the distribution of K+, tetraphenylphosphonium, Ca2+, Sr2+ and Mn2+. (1) The matrix concentration of divalent cations has been calculated from the total cation uptake, from the increase of matrix volume and from the ESR sextet signal of Mn(H2O)L2+. The [cat2+]i based on osmotic data is about five times higher than that based on ESR measurements. The [cat2+]i based on total uptake is much higher than that based on osmotic data at low cation/protein ratios. (2) In the presence of 10 mM acetate the maximal deltapsi on Ca2+ is about 130 mV and on Sr2+ is 95 mV. Deltapsi on Mn2+ is 91 or 109 mV, according to whether [cat2+-a)i is calculated from ESR or osmotic data. Under the same conditions, deltapH is about 60 mV. Hence delta approximately muH on divalent cations is between 151 and 190 mV. (3) Deltapsi on K+, in valinomycin treated mitochondria with 10 mM acetate or 2 mM Pi, drops from 200 mV, at low [K+]0 to almost zero parallel to the increase of [K+]0. DeltapH is 30 mV at low [K+]0 and about 42 mV at 600 muM K+. Hence delta approximately muH drops from 22m mV lower values with the increase of [K+]0. (4) Maximal deltapsi on triphenylmethylphosphonium is 140 mV. (5) When delta approximately muH is measured simultaneously on divalent cations and on K+, the values on K+ tend to approach those on Ca2+ while those on Sr2+ are about 50 mV lower. (6) It is concluded that the steady state mitochondrial energy potential is equivalent to a delta approximately muH between 150 and approx. 190 mV."}
{"id": "PMID:12815", "title": "Role of protein dissociation in the transport of acidic amino acids by the Ehrlich ascites tumor cell.", "content": "The pH profile for the uptake of L-glutamic acid by the Ehrlich ascites tumor cell arises largely as a sum of the decline with falling pH of a slow, Na+-dependent uptake by System A, and an increasing uptake by Na+-independent System L. The latter maximizes at about pH 4.5, following approximately the titration curve of the distal carboxyl group. This shift in route of uptake was verified by (a) a declining Na+-dependent component, (b) an almost corresponding decline in the 2-(methylamino)-isobutyric acid-inhibitable component, (c) a rising component inhibited by 2-aminonorbornane-2-carboxylic acid. Other amino acids recognized as principally reactive with Systems A or L yielded corresponding inhibitory effects with some conspicious exceptions: 2-Aminoisobutyric acid and even glycine become better substrates of System L as the pH is lowered; hence their inhibitory action on glutamic acid uptake is not lost. The above results were characterized by generally consistent relations among the half-saturation concentrations of the interacting amino acids with respect to: their own uptake, their inhibition of the uptake, one by another, and their trans stimulation of exodus, one by another. A small Na+-dependent component of uptake retained by L-glutamic acid but not by D-glutamic acid at pH 4.5 is inhibitable by methionine but by neither 2-(methylamino)-isobutyric acid nor the norbornane amino acid. We provisionally identified this component with System ASC, which transports L-glutamine throughout the pH range studied. No transport activity specific to the anionic amino acids was detected, and the unequivocally anionic cysteic acid showed neither significant mediated uptake nor inhibition of the uptake of glutamic aic or of the norbornane amino acid. The dicarboxylic amino acids take the sequence, aspartic acid less than glutamic acid less than alpha-aminoadipic acid less than S-carboxymethylcysteine, in their rate of mediated, Na+-independent uptake at low pH. Diiodotyrosine and two dissimilas isomers  of nitrotyrosine also show acceleration of uptake as the phenolate group on the sidechain is protonated, a result indicating that the acidic group need not be a carboxyl group and need not take a specific position in space to be accepted at the receptor site L. The presence of the carboxyl group does not upset the normal stereospecificity of System L until it falls on the beta-carbon in aspartic acid; even then it is the presence of the carbonyl group and not of the intact carboxyl group nor of its hydroxyl group that cancels out the stereospecificity, as was shown by the absence of normal stereospecificity for aspartic acid and asparagine and its presence in glutamic acid, homoserine and glutamine. In agreement, the uptak of aspartic acid is peculiarly sensitive to the presence of an alpha-methyl group or of other structures that modify the orientation of the sidechain.", "contents": "Role of protein dissociation in the transport of acidic amino acids by the Ehrlich ascites tumor cell. The pH profile for the uptake of L-glutamic acid by the Ehrlich ascites tumor cell arises largely as a sum of the decline with falling pH of a slow, Na+-dependent uptake by System A, and an increasing uptake by Na+-independent System L. The latter maximizes at about pH 4.5, following approximately the titration curve of the distal carboxyl group. This shift in route of uptake was verified by (a) a declining Na+-dependent component, (b) an almost corresponding decline in the 2-(methylamino)-isobutyric acid-inhibitable component, (c) a rising component inhibited by 2-aminonorbornane-2-carboxylic acid. Other amino acids recognized as principally reactive with Systems A or L yielded corresponding inhibitory effects with some conspicious exceptions: 2-Aminoisobutyric acid and even glycine become better substrates of System L as the pH is lowered; hence their inhibitory action on glutamic acid uptake is not lost. The above results were characterized by generally consistent relations among the half-saturation concentrations of the interacting amino acids with respect to: their own uptake, their inhibition of the uptake, one by another, and their trans stimulation of exodus, one by another. A small Na+-dependent component of uptake retained by L-glutamic acid but not by D-glutamic acid at pH 4.5 is inhibitable by methionine but by neither 2-(methylamino)-isobutyric acid nor the norbornane amino acid. We provisionally identified this component with System ASC, which transports L-glutamine throughout the pH range studied. No transport activity specific to the anionic amino acids was detected, and the unequivocally anionic cysteic acid showed neither significant mediated uptake nor inhibition of the uptake of glutamic aic or of the norbornane amino acid. The dicarboxylic amino acids take the sequence, aspartic acid less than glutamic acid less than alpha-aminoadipic acid less than S-carboxymethylcysteine, in their rate of mediated, Na+-independent uptake at low pH. Diiodotyrosine and two dissimilas isomers  of nitrotyrosine also show acceleration of uptake as the phenolate group on the sidechain is protonated, a result indicating that the acidic group need not be a carboxyl group and need not take a specific position in space to be accepted at the receptor site L. The presence of the carboxyl group does not upset the normal stereospecificity of System L until it falls on the beta-carbon in aspartic acid; even then it is the presence of the carbonyl group and not of the intact carboxyl group nor of its hydroxyl group that cancels out the stereospecificity, as was shown by the absence of normal stereospecificity for aspartic acid and asparagine and its presence in glutamic acid, homoserine and glutamine. In agreement, the uptak of aspartic acid is peculiarly sensitive to the presence of an alpha-methyl group or of other structures that modify the orientation of the sidechain."}
{"id": "PMID:12816", "title": "Proton transport by gastric membrane vesicles.", "content": "A highly purified membrane fraction was derived from hog gastric mucosa by a combination of differential and density gradient centrifugation and free flow electrophoresis. This final fraction was 35-fold enriched with respect to cation activated ouabain-insensitive ATPase. Antibody against this fraction was shown to be bound to the luminal surface of the gastric glands. The addition of ATP to this fraction or the density gradient fraction resulted in H+ uptake into an osmotically sensitive space. The apparent Km for ATP was 1.7-10(-4) M in the absence of a K+ gradient similar to that found for ATPase activity. The reaction is specific for ATP and requires cation in the sequence K+ greater than Rb+ greater than Cs+ greater than Na+ greater than Li+ and inhibited by ATPase inhibitors such as N,N'-dicylclohexyl-carbodiimide. Maximal H+ uptake occurs with an outward K+ gradient but the minimal apparent KA is found in the absence of a K+ gradient. The pH optimum for H+ uptake is between 5.8 and 6.2 which corresponds to the pH range for phosphroylation of the enzyme, but is considerably less than the pH maximum of the K+ dependent dephosphorylation. In the presence of an inward K+ gradient, protonophores such as tetrachlorsalicylanilide only partially abolish the H+ gradient but valinomycin dissipates 75% of the gradient, and nigericin abolishes the gradient. The vesicles therefore have a low K+ conductance but a measurable H+ conductance, hence a K+ gradient can produce an H+ gradient in the presence of valinomycin. The uptake and spontaneous leak of H+ are temperature sensitive with a similar transition temperature. Ultraviolet irradiation inactivates ATPase and proton transport at the same rate, approximately at twice the rate of p-nitrophenylphosphatase inactivation. It is concluded that H+ uptake by these vesicles is probably due to a dimeric (H+ + K+)-ATPase and is probably non-electrogenic.", "contents": "Proton transport by gastric membrane vesicles. A highly purified membrane fraction was derived from hog gastric mucosa by a combination of differential and density gradient centrifugation and free flow electrophoresis. This final fraction was 35-fold enriched with respect to cation activated ouabain-insensitive ATPase. Antibody against this fraction was shown to be bound to the luminal surface of the gastric glands. The addition of ATP to this fraction or the density gradient fraction resulted in H+ uptake into an osmotically sensitive space. The apparent Km for ATP was 1.7-10(-4) M in the absence of a K+ gradient similar to that found for ATPase activity. The reaction is specific for ATP and requires cation in the sequence K+ greater than Rb+ greater than Cs+ greater than Na+ greater than Li+ and inhibited by ATPase inhibitors such as N,N'-dicylclohexyl-carbodiimide. Maximal H+ uptake occurs with an outward K+ gradient but the minimal apparent KA is found in the absence of a K+ gradient. The pH optimum for H+ uptake is between 5.8 and 6.2 which corresponds to the pH range for phosphroylation of the enzyme, but is considerably less than the pH maximum of the K+ dependent dephosphorylation. In the presence of an inward K+ gradient, protonophores such as tetrachlorsalicylanilide only partially abolish the H+ gradient but valinomycin dissipates 75% of the gradient, and nigericin abolishes the gradient. The vesicles therefore have a low K+ conductance but a measurable H+ conductance, hence a K+ gradient can produce an H+ gradient in the presence of valinomycin. The uptake and spontaneous leak of H+ are temperature sensitive with a similar transition temperature. Ultraviolet irradiation inactivates ATPase and proton transport at the same rate, approximately at twice the rate of p-nitrophenylphosphatase inactivation. It is concluded that H+ uptake by these vesicles is probably due to a dimeric (H+ + K+)-ATPase and is probably non-electrogenic."}
{"id": "PMID:12817", "title": "Effect of temperature and protonation upon the conformation of 2'-o-methyladenosine. Correlation of conformational parameters in purine nucleosides.", "content": "Proton magnetic resonance studies of 2'-o-methyladenosine in 2H2O have been carried out at variable temperature and p2H. The chemical shifts and H-H coupling constants are discussed in terms of the molecular conformation. Comparison of the data with those of adenosine reveals that 2'-O-methylation has little influence on the conformation. At neutral p2H where the adenine base is not protonated, the molecules favor a 2' endo, gauche-gauche conformation. Protonation of the base at the N(1) position leads to a decrease in the 2' endo, gauche-gauche bias. The data for 2'-O-methyladenosine and adenosine, as well as for several other purine derivatives, reveal the presence of a correlation between the sugar pucker and the C(5')-C(4') conformer distribution which is the inverse of the correlation previously reported for pyrimidine derivatives.", "contents": "Effect of temperature and protonation upon the conformation of 2'-o-methyladenosine. Correlation of conformational parameters in purine nucleosides. Proton magnetic resonance studies of 2'-o-methyladenosine in 2H2O have been carried out at variable temperature and p2H. The chemical shifts and H-H coupling constants are discussed in terms of the molecular conformation. Comparison of the data with those of adenosine reveals that 2'-O-methylation has little influence on the conformation. At neutral p2H where the adenine base is not protonated, the molecules favor a 2' endo, gauche-gauche conformation. Protonation of the base at the N(1) position leads to a decrease in the 2' endo, gauche-gauche bias. The data for 2'-O-methyladenosine and adenosine, as well as for several other purine derivatives, reveal the presence of a correlation between the sugar pucker and the C(5')-C(4') conformer distribution which is the inverse of the correlation previously reported for pyrimidine derivatives."}
{"id": "PMID:12818", "title": "[Hydrogen-adduct radicals in thymidine and thymidine 5'-monophosphate photosensitized by proflavin. Protection by sulfur compounds (author's transl)].", "content": "At pH values 5 and 9, the influence of cysteine, cystine, 3-mercaptopropionic acid and S-methylcysteine on the induction of H-adduct radicals in thymidine and thymidine 5'-monophosphate photosensitized by proflavin is investigated. The results obtained indicate that efficient protection is given when the electrostatic interactions between the charged groups of the molecules present allow the close proximity of a thiol or a disulfide bridge and the proflavin - DNAs complex constituent. The scheme proposed for the mechanism involves the capture by the protector of an electron or a proton, indispensable intermediates in the formation of the H-adduct radicals.", "contents": "[Hydrogen-adduct radicals in thymidine and thymidine 5'-monophosphate photosensitized by proflavin. Protection by sulfur compounds (author's transl)]. At pH values 5 and 9, the influence of cysteine, cystine, 3-mercaptopropionic acid and S-methylcysteine on the induction of H-adduct radicals in thymidine and thymidine 5'-monophosphate photosensitized by proflavin is investigated. The results obtained indicate that efficient protection is given when the electrostatic interactions between the charged groups of the molecules present allow the close proximity of a thiol or a disulfide bridge and the proflavin - DNAs complex constituent. The scheme proposed for the mechanism involves the capture by the protector of an electron or a proton, indispensable intermediates in the formation of the H-adduct radicals."}
{"id": "PMID:12819", "title": "Differential, structure-dependent susceptibility of poly(A) and RNA to monomeric and dimeric pancreatic ribonuclease A.", "content": "Cross-linked dimers of bovine RNAase A are definitely more efficient than monomers at degrading polyadenylic acid under conditions of ionic strength and pH, where the polymer assumes either a double-helical or an ordered single-stranded, base-stacked structure. The opposite occurs, i.e., monomers of RNAase A are definitely more active than dimers,when poly(A) is digested by the two enzyme species under conditions where the conformation of the polymer is essentially that of a random coil. The same pattern of events occurs when total RNA from Escherichia coli or single-stranded RNA of f2 sus11 bacteriophage are used as substrates under opposite ionic-strength conditions. In the presence of high salt concentrations, favouring the formation and the stability of a secondary structure in self-complementary sequences of RNA, the ribonucleic acids are degraded at a higher rate by dimers than by monomers of bovine RNAase A. The opposite occurs in the presence of very low salt concentrations, i.e. when the RNAs are in solution presumably as random coils. These observations are discussed in the light of a hypothesis already advanced to understand the mechanism of enzymic degradation of secondary structures of polyribonucleotides.", "contents": "Differential, structure-dependent susceptibility of poly(A) and RNA to monomeric and dimeric pancreatic ribonuclease A. Cross-linked dimers of bovine RNAase A are definitely more efficient than monomers at degrading polyadenylic acid under conditions of ionic strength and pH, where the polymer assumes either a double-helical or an ordered single-stranded, base-stacked structure. The opposite occurs, i.e., monomers of RNAase A are definitely more active than dimers,when poly(A) is digested by the two enzyme species under conditions where the conformation of the polymer is essentially that of a random coil. The same pattern of events occurs when total RNA from Escherichia coli or single-stranded RNA of f2 sus11 bacteriophage are used as substrates under opposite ionic-strength conditions. In the presence of high salt concentrations, favouring the formation and the stability of a secondary structure in self-complementary sequences of RNA, the ribonucleic acids are degraded at a higher rate by dimers than by monomers of bovine RNAase A. The opposite occurs in the presence of very low salt concentrations, i.e. when the RNAs are in solution presumably as random coils. These observations are discussed in the light of a hypothesis already advanced to understand the mechanism of enzymic degradation of secondary structures of polyribonucleotides."}
{"id": "PMID:12820", "title": "Effects of stereochemical structures of tetrahydrobiopterin on tyrosine hydroxylase.", "content": "1. Four stereochemical isomers of tetrahydrobiopterin, i.e., 6-L-erythro-, 6-D-erythro-, 6-L-threo-, or 6-D-threo-1,2-dihydroxypropyltetrahydropterin, have been synthesized and used as cofactors for tyrosine hydroxylase (EC 1.14.18.-) purified from the soluble fraction of bovine adrenal medulla. The L-erythro- (the putative natural cofactor) and D-threo isomers showed a striking similarity in their cofactor activities for tyrosine hydroxylase; the remaining two isomeric tetrahydrobiopterins, D-erythro and L-threo isomers, also had very similar cofactor characteristics. 2. The Km values of the L-erythro and D-threo isomers as cofactor were found to be dependent on their concentrations. When their concentrations were below 100 muM, the Km values of the L-erythro and D-threo isomers were fairly low (about 20 muM). However, the Km values were markedly higher (about 150 muM) at concentrations above 100 muM. The same kinetic behavior was also observed with the tetrahydrobiopterin prepared from a natural source (bullfrog). In contrast, the Km value of the L-threo or D-erythro isomer was found to be independent of the concentration and remained constant throughout the concentration examined. 3. The Km values of tyrosine did not show much difference (from 20 muM to 30 muM) with respect to the structure of the four isomeric cofactors. At high concentrations tyrosine inhibited the enzymatic reaction with any one of the four tetrahydrobiopterin cofactors. 4. Oxygen at high concentrations was also inhibitory with any one of the four stereochemical isomers as cofactor. Approximate Km values for oxygen with the tetrahydrobiopterins as cofactor were 1-5%. 5. In contrast to the four isomers of tetrahydrobiopterin, when 6-methyltetrahydropterin or 6,7-dimethyltetrahydropterin was used as cofactor tyrosine or oxygen did no inhibit the enzymatic reaction at high concentrations, and the Km values toward the pterin cofactor, tyrosine, and oxygen were significantly higher than the Km values with the tetrahydrobiopterins as cofactor.", "contents": "Effects of stereochemical structures of tetrahydrobiopterin on tyrosine hydroxylase. 1. Four stereochemical isomers of tetrahydrobiopterin, i.e., 6-L-erythro-, 6-D-erythro-, 6-L-threo-, or 6-D-threo-1,2-dihydroxypropyltetrahydropterin, have been synthesized and used as cofactors for tyrosine hydroxylase (EC 1.14.18.-) purified from the soluble fraction of bovine adrenal medulla. The L-erythro- (the putative natural cofactor) and D-threo isomers showed a striking similarity in their cofactor activities for tyrosine hydroxylase; the remaining two isomeric tetrahydrobiopterins, D-erythro and L-threo isomers, also had very similar cofactor characteristics. 2. The Km values of the L-erythro and D-threo isomers as cofactor were found to be dependent on their concentrations. When their concentrations were below 100 muM, the Km values of the L-erythro and D-threo isomers were fairly low (about 20 muM). However, the Km values were markedly higher (about 150 muM) at concentrations above 100 muM. The same kinetic behavior was also observed with the tetrahydrobiopterin prepared from a natural source (bullfrog). In contrast, the Km value of the L-threo or D-erythro isomer was found to be independent of the concentration and remained constant throughout the concentration examined. 3. The Km values of tyrosine did not show much difference (from 20 muM to 30 muM) with respect to the structure of the four isomeric cofactors. At high concentrations tyrosine inhibited the enzymatic reaction with any one of the four tetrahydrobiopterin cofactors. 4. Oxygen at high concentrations was also inhibitory with any one of the four stereochemical isomers as cofactor. Approximate Km values for oxygen with the tetrahydrobiopterins as cofactor were 1-5%. 5. In contrast to the four isomers of tetrahydrobiopterin, when 6-methyltetrahydropterin or 6,7-dimethyltetrahydropterin was used as cofactor tyrosine or oxygen did no inhibit the enzymatic reaction at high concentrations, and the Km values toward the pterin cofactor, tyrosine, and oxygen were significantly higher than the Km values with the tetrahydrobiopterins as cofactor."}
{"id": "PMID:12821", "title": "Partial purification and properties of a cyclic 3',5'-AMP-independent protein kinase from rat liver.", "content": "1. A cyclic 3',5'-AMP-independent protein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) from rat liver cytosol was partially purified and characterized. Purification by (NH4)2SO4 precipitation, DEAE-cellulose, Bio Gel A-0.5 m and cellulose phosphate chromatography increased the specific activity about 700-fold. 2. An endogenous protein substrate was closely associated with the protein kinase and was not separable from this enzyme up to the cellulose phosphate stage. After phosphorylation, chromatography with Bio Gel A-0.5 m partially separated this endogenous phosphoprotein from the enzyme activity; this dissociation had no apparent effect on kinase activity with casein or phosvitin as substrates, or on the apparent molecular weight of the enzyme (approx. 158,000). 3. This protein kinase with casein, phosvitin, or the endogenous substrate was totally insensitive to the thiol reagents, p-hydroxymercuribenzoate, 5,5'-dithiobis(2-nitrobenzoic acid), iodoacetamide, and N-ethylmaleimide. The enzyme was also unaffected by cyclic 3',5'-AMP, heat-stable protein kinase inhibitor, and the regulatory subunit of a cyclic 3',5'-AMP-dependent protein kinase.", "contents": "Partial purification and properties of a cyclic 3',5'-AMP-independent protein kinase from rat liver. 1. A cyclic 3',5'-AMP-independent protein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) from rat liver cytosol was partially purified and characterized. Purification by (NH4)2SO4 precipitation, DEAE-cellulose, Bio Gel A-0.5 m and cellulose phosphate chromatography increased the specific activity about 700-fold. 2. An endogenous protein substrate was closely associated with the protein kinase and was not separable from this enzyme up to the cellulose phosphate stage. After phosphorylation, chromatography with Bio Gel A-0.5 m partially separated this endogenous phosphoprotein from the enzyme activity; this dissociation had no apparent effect on kinase activity with casein or phosvitin as substrates, or on the apparent molecular weight of the enzyme (approx. 158,000). 3. This protein kinase with casein, phosvitin, or the endogenous substrate was totally insensitive to the thiol reagents, p-hydroxymercuribenzoate, 5,5'-dithiobis(2-nitrobenzoic acid), iodoacetamide, and N-ethylmaleimide. The enzyme was also unaffected by cyclic 3',5'-AMP, heat-stable protein kinase inhibitor, and the regulatory subunit of a cyclic 3',5'-AMP-dependent protein kinase."}
{"id": "PMID:12822", "title": "Stereospecificity of the hydrogen transfer catalyzed by human placental aldose reductase.", "content": "Placental aldose reductase (EC 1.1.1.21) was incubated with glucose in the presence of [4A-2H] NADPH prepared in the oxidation of [2-2H] isocitrate by isocitrate dehydrogenase (EC 1.1.1.42) or [4B-2H] NADPH prepared in the oxidation of [1-2H] glucose-6-phosphate dehydrogenase (EC 1.1.1.49). The sorbitol formed from [4A-2H] NADPH contained deuterium and from [4B-2H] NADPH it did not. Therefore, aldose reductase in an A-type enzyme.", "contents": "Stereospecificity of the hydrogen transfer catalyzed by human placental aldose reductase. Placental aldose reductase (EC 1.1.1.21) was incubated with glucose in the presence of [4A-2H] NADPH prepared in the oxidation of [2-2H] isocitrate by isocitrate dehydrogenase (EC 1.1.1.42) or [4B-2H] NADPH prepared in the oxidation of [1-2H] glucose-6-phosphate dehydrogenase (EC 1.1.1.49). The sorbitol formed from [4A-2H] NADPH contained deuterium and from [4B-2H] NADPH it did not. Therefore, aldose reductase in an A-type enzyme."}
{"id": "PMID:12823", "title": "Metal ion-induced conformational changes in Escherichia coli alkaline phosphatase.", "content": "Ultraviolet difference spectra are produced by the binding of divalent metal ions to metal-free alkaline phosphatase (EC 3.1.3.1). The interaction of the apoprotein with Zn2+, Mn2+, Co2+ and Cd2+, which induce the tight binding of one phosphate ion per dimer, give distinctly different ultraviolet spectra changes from Ni2+ and Hg2+ which do not induce phosphate binding. Spectrophotometric titrations at alkaline pH of various metallo-enzymes reveal a smaller number of ionizable tyrosines and a greater stability towards alkaline denaturation in the Zn2+- and Mn2+-enzymes than in the Ni2+-, Hg2+- and apoenzymes. The Zn2+- and Mn2+-enzymes have CD spectra in the region of the aromatic transitions that are different from the CD spectra of the Ni2+-, Hg2+- and apoenzymes. Modifications of arginines with 2,3-butanedione show that a smaller number of arginine residues are modified in the Zn2+-enzyme than in the Hg2+-enzyme. The presented data indicate that alkaline phosphatase from Escherichia coli must have a well-defined conformation in order to bind phosphate. Some metal ions (i.e. Zn2+, Co2+, Mn2+ and Cd2+), when interacting with the apoenzyme, alter the conformation of the protein molecule in such a way that it is able to interact with substrate molecules, while other metal ions (i.e. Ni2+ and Hg2+) are incapable of inducing the appropriate conformational change of the apoenzyme. These findings suggest an important structural function of the first two tightly bound metal ions in enzyme.", "contents": "Metal ion-induced conformational changes in Escherichia coli alkaline phosphatase. Ultraviolet difference spectra are produced by the binding of divalent metal ions to metal-free alkaline phosphatase (EC 3.1.3.1). The interaction of the apoprotein with Zn2+, Mn2+, Co2+ and Cd2+, which induce the tight binding of one phosphate ion per dimer, give distinctly different ultraviolet spectra changes from Ni2+ and Hg2+ which do not induce phosphate binding. Spectrophotometric titrations at alkaline pH of various metallo-enzymes reveal a smaller number of ionizable tyrosines and a greater stability towards alkaline denaturation in the Zn2+- and Mn2+-enzymes than in the Ni2+-, Hg2+- and apoenzymes. The Zn2+- and Mn2+-enzymes have CD spectra in the region of the aromatic transitions that are different from the CD spectra of the Ni2+-, Hg2+- and apoenzymes. Modifications of arginines with 2,3-butanedione show that a smaller number of arginine residues are modified in the Zn2+-enzyme than in the Hg2+-enzyme. The presented data indicate that alkaline phosphatase from Escherichia coli must have a well-defined conformation in order to bind phosphate. Some metal ions (i.e. Zn2+, Co2+, Mn2+ and Cd2+), when interacting with the apoenzyme, alter the conformation of the protein molecule in such a way that it is able to interact with substrate molecules, while other metal ions (i.e. Ni2+ and Hg2+) are incapable of inducing the appropriate conformational change of the apoenzyme. These findings suggest an important structural function of the first two tightly bound metal ions in enzyme."}
{"id": "PMID:12824", "title": "Rat intestinal phosphodiesterase II. Properties of the highly purified enzyme and its inactivation by iodoacetic acid.", "content": "A highly purifed preparation of rat intestinal phosphodiesterase II (oligonucleate 3'-nucleotidohydrolase, EC 3.1.4.18) has been studied using a synthetic substrate, thymidine 3'(2,4-dinitrophenyl) phosphate. The enzyme was most active between pH 6.1 and pH 6.7 and was inhibited by Cu2+ and Zn2+ but unaffected by EDTA, Mg2+, Co2+, and Ni2+. The reaction rate decreased at high levels of enzyme because of competitive inhibition by deoxythymidine 3'-phosphate, a reaction product, which showed a Ki of 2-10(-5) M. The molecular weight of the enzyme by gel-filtration was 150 000-170 000. In electrofocusing experiments multiple peaks of activity were found at pH 3.4, 4.2-4.5and 7.2. Polyacrylamide gel electrophoresis of freshly purified phosphodiesterase II showed up to 10 protein bands in the gels. If the preparations were stored at 4 degrees C for some time only one or two bands appeared. Investigation of the reaction of rat intestinal phosphodiesterase II with a number of possible phosphodiesterase substrates indicated that the enzyme required a nucleoside 3'-phosphoryl residue for the initiation of hydrolysis. Thus compounds such as NAD, ATP, bis-(p-nitrophenyl)phosphate, thymidine 5'-(p-nitrophenyl)phosphate, glycerylphosphorylcholine, guanylyl-(2' leads to 5')-adenosine and 3',5'-cyclic AMP which contain phosphodiester bonds, nevertheless were not substrates for the enzyme. The enzyme was inhibited reverisbly by p-chloromercuribenzoate and p-chloromercuriphenylsulfonate and inactivated irreversibly by iodoacetic acid. Activity of the phosphodiesterase II was reduced to 50% by incubation with 2.0-10(-3)--5.0-10(-3) M iodoacetate for 20--30 min at 24 degrees C at pH 5.0--6.1. Iodoacetamide had no effect. The degree of inactivation by iodoacetate was reduced by the presence of a substrate for the enzyme or, more effectively by deoxythymidine 3'-phosphate, a competitive inhibitor. It is concluded that iodoacetic acid alkylates an essential residue at the active centre of the enzyme.", "contents": "Rat intestinal phosphodiesterase II. Properties of the highly purified enzyme and its inactivation by iodoacetic acid. A highly purifed preparation of rat intestinal phosphodiesterase II (oligonucleate 3'-nucleotidohydrolase, EC 3.1.4.18) has been studied using a synthetic substrate, thymidine 3'(2,4-dinitrophenyl) phosphate. The enzyme was most active between pH 6.1 and pH 6.7 and was inhibited by Cu2+ and Zn2+ but unaffected by EDTA, Mg2+, Co2+, and Ni2+. The reaction rate decreased at high levels of enzyme because of competitive inhibition by deoxythymidine 3'-phosphate, a reaction product, which showed a Ki of 2-10(-5) M. The molecular weight of the enzyme by gel-filtration was 150 000-170 000. In electrofocusing experiments multiple peaks of activity were found at pH 3.4, 4.2-4.5and 7.2. Polyacrylamide gel electrophoresis of freshly purified phosphodiesterase II showed up to 10 protein bands in the gels. If the preparations were stored at 4 degrees C for some time only one or two bands appeared. Investigation of the reaction of rat intestinal phosphodiesterase II with a number of possible phosphodiesterase substrates indicated that the enzyme required a nucleoside 3'-phosphoryl residue for the initiation of hydrolysis. Thus compounds such as NAD, ATP, bis-(p-nitrophenyl)phosphate, thymidine 5'-(p-nitrophenyl)phosphate, glycerylphosphorylcholine, guanylyl-(2' leads to 5')-adenosine and 3',5'-cyclic AMP which contain phosphodiester bonds, nevertheless were not substrates for the enzyme. The enzyme was inhibited reverisbly by p-chloromercuribenzoate and p-chloromercuriphenylsulfonate and inactivated irreversibly by iodoacetic acid. Activity of the phosphodiesterase II was reduced to 50% by incubation with 2.0-10(-3)--5.0-10(-3) M iodoacetate for 20--30 min at 24 degrees C at pH 5.0--6.1. Iodoacetamide had no effect. The degree of inactivation by iodoacetate was reduced by the presence of a substrate for the enzyme or, more effectively by deoxythymidine 3'-phosphate, a competitive inhibitor. It is concluded that iodoacetic acid alkylates an essential residue at the active centre of the enzyme."}
{"id": "PMID:12825", "title": "Oxidation of methyl derivatives of pteridin-4-one, lumazine and related pteridines by bovine milk xanthine oxidase.", "content": "1. Pteridin-4-ones, methylated at nitrogen or carbon, N-methylated lumazines and related oxopteridines were studied as substrates of a highly purified bovine milk xanthine oxidase (xanthine : oxygen oxidoreductase, EC 1.2.3.2). 2. The enzyme can oxidise at high rates both uncharged and anionic substrates. Variation of enzymic activity with pH is mainly due to pH-dependent changes in the active enzymic center. 3. Milk xanthine oxidases at different stages of purification convert pteridin-4-one into the 4,7-dione (compound 13 in this article). 4. Methylation at C-6 in the pyrazine moiety enhances enzymic attack at C-2 in the pyrimidine ring. N-Methylation may increase or reduce rates of oxidation. 5. For oxidation at C-2, the most favorable form of the substrate bears a double bond at C(2) = N(3). Attack at C-7 is enhanced strongly in structures bearing a double bond at C(6) = C(7). 6. In general, pteridines react with xanthine oxidase as non-hydrated molecules. However, oxidation of 8-methyllumazine at C-7 may take place by dehydrogenation of the 7-CHOH group of the covalently hydrated molecule.", "contents": "Oxidation of methyl derivatives of pteridin-4-one, lumazine and related pteridines by bovine milk xanthine oxidase. 1. Pteridin-4-ones, methylated at nitrogen or carbon, N-methylated lumazines and related oxopteridines were studied as substrates of a highly purified bovine milk xanthine oxidase (xanthine : oxygen oxidoreductase, EC 1.2.3.2). 2. The enzyme can oxidise at high rates both uncharged and anionic substrates. Variation of enzymic activity with pH is mainly due to pH-dependent changes in the active enzymic center. 3. Milk xanthine oxidases at different stages of purification convert pteridin-4-one into the 4,7-dione (compound 13 in this article). 4. Methylation at C-6 in the pyrazine moiety enhances enzymic attack at C-2 in the pyrimidine ring. N-Methylation may increase or reduce rates of oxidation. 5. For oxidation at C-2, the most favorable form of the substrate bears a double bond at C(2) = N(3). Attack at C-7 is enhanced strongly in structures bearing a double bond at C(6) = C(7). 6. In general, pteridines react with xanthine oxidase as non-hydrated molecules. However, oxidation of 8-methyllumazine at C-7 may take place by dehydrogenation of the 7-CHOH group of the covalently hydrated molecule."}
{"id": "PMID:12826", "title": "Purification and properties of rabbit heart muscle aldolase.", "content": "Fructose diphosphate aldolase (D-fructose-1,6-biphosphate D-glyceraldehyde-3-phosphate lyase, EC 4.1.2.13) from rabbit heart has been purified and obtained in crystalline form. The preparations are homogeneous on the basis of disc gel electrophoresis and ultracentrifugation. The catalytic and the molecular properties indicate that this is aldolase A. A comparison was made between rabbit heart aldolase and the rabbit muscle enzyme. The sedimentation coefficient, energy of activation and Michaelis constant for Fru-1,6-P2 were found to be identical with the values obtained for the muscle enzyme. As in case of the muscle enzyme, heart aldolase was found to have a broad pH optimum, remarkable stability over a wide pH range, and the ability to form a Schiff base intermediate with dihydroxyacetone phosphate upon reduction with borohydride. Cleavage of the methionyl bonds with CNBr yields the same pattern as obtained with the muscle enzyme.", "contents": "Purification and properties of rabbit heart muscle aldolase. Fructose diphosphate aldolase (D-fructose-1,6-biphosphate D-glyceraldehyde-3-phosphate lyase, EC 4.1.2.13) from rabbit heart has been purified and obtained in crystalline form. The preparations are homogeneous on the basis of disc gel electrophoresis and ultracentrifugation. The catalytic and the molecular properties indicate that this is aldolase A. A comparison was made between rabbit heart aldolase and the rabbit muscle enzyme. The sedimentation coefficient, energy of activation and Michaelis constant for Fru-1,6-P2 were found to be identical with the values obtained for the muscle enzyme. As in case of the muscle enzyme, heart aldolase was found to have a broad pH optimum, remarkable stability over a wide pH range, and the ability to form a Schiff base intermediate with dihydroxyacetone phosphate upon reduction with borohydride. Cleavage of the methionyl bonds with CNBr yields the same pattern as obtained with the muscle enzyme."}
{"id": "PMID:12827", "title": "A cis-trans isomerising activity of Escherichia coli. Isomerization from 2-(2-furyl)-3-cis-(5-nitro-2-furyl) acrylamide (furylfuramide) to its trans isomer.", "content": "The soluble enzyme fraction derived from Escherichia coli K-12 JE2100 cells was found to exhibit, in addition to Nadh- and NADPH-dependent reductase activities, NADH-dependent cis-trans isomerising activity toward 2-(2-furyl-3-(5-nitro-2-furyl)acrylamide leading to a specific change in geometrical configuration of the vinyl group at the 2-position from cis to trans but not in the reverse direction. This furylfuramide-isomerising action of bacteria was dicoumarol insensitive, and did not require glutathione for full activity. The particulate enzyme fraction derived from JE2100 cells, although it showed little reductase activity toward furylfuramide in the presence of either NADH or NADPH, revealed an isomerising activity in the presence of NADH.", "contents": "A cis-trans isomerising activity of Escherichia coli. Isomerization from 2-(2-furyl)-3-cis-(5-nitro-2-furyl) acrylamide (furylfuramide) to its trans isomer. The soluble enzyme fraction derived from Escherichia coli K-12 JE2100 cells was found to exhibit, in addition to Nadh- and NADPH-dependent reductase activities, NADH-dependent cis-trans isomerising activity toward 2-(2-furyl-3-(5-nitro-2-furyl)acrylamide leading to a specific change in geometrical configuration of the vinyl group at the 2-position from cis to trans but not in the reverse direction. This furylfuramide-isomerising action of bacteria was dicoumarol insensitive, and did not require glutathione for full activity. The particulate enzyme fraction derived from JE2100 cells, although it showed little reductase activity toward furylfuramide in the presence of either NADH or NADPH, revealed an isomerising activity in the presence of NADH."}
{"id": "PMID:12828", "title": "Influence of 8-substitutes on the oxidation of hypoxanthine and 6-thioxopurine by bovine milk xanthine oxidase.", "content": "1. The influence of 8-substituents was studied on the rate of oxidation of hypoxanthine and 6-thioxopurine by bovine milk xanthine oxidase (EC 1.2.3.2). 2. An 8-methyl group does not alter the rate of oxidation of hypoxanthine materially, but an 8-phenyl substituent reduces it markedly. This is ascribed to inhibition of the tautomerisation process, responsible for substrate activation, prior to oxidation. 3. In contrast, the 8-phenyl group in 3-methyl-8-phenylhypoxanthine enhances the rate, presumably by binding to a hydrophobic site near the enzymaic center. 4. An 8-phenyl group in 6-thioxopurine markedly increases the rate of enzymaic oxidation. Probably the aromatic substituent diverts anion formation to the imidazole ring. In contrast, ionisation of 8-methyl-6-thioxopurine involves the pyrimidine moiety, thus rendering enzymic attack at position 2 more difficult.", "contents": "Influence of 8-substitutes on the oxidation of hypoxanthine and 6-thioxopurine by bovine milk xanthine oxidase. 1. The influence of 8-substituents was studied on the rate of oxidation of hypoxanthine and 6-thioxopurine by bovine milk xanthine oxidase (EC 1.2.3.2). 2. An 8-methyl group does not alter the rate of oxidation of hypoxanthine materially, but an 8-phenyl substituent reduces it markedly. This is ascribed to inhibition of the tautomerisation process, responsible for substrate activation, prior to oxidation. 3. In contrast, the 8-phenyl group in 3-methyl-8-phenylhypoxanthine enhances the rate, presumably by binding to a hydrophobic site near the enzymaic center. 4. An 8-phenyl group in 6-thioxopurine markedly increases the rate of enzymaic oxidation. Probably the aromatic substituent diverts anion formation to the imidazole ring. In contrast, ionisation of 8-methyl-6-thioxopurine involves the pyrimidine moiety, thus rendering enzymic attack at position 2 more difficult."}
{"id": "PMID:12829", "title": "Transhydrogenase activity in the marine bacterium Beneckea natriegens.", "content": "The marine bacterium, Beneckea natriegens, which has previously been reported not to form transhydrogenase, has been shown to synthesize a soluble energy-independent transhydrogenase (NADPH:NADP+ oxidoreductase, EC 1.6.1.1), though no energy-linked activity could be detected. The transhydrogenase is induced maximally in stationary phase cells and its formation is 70-90% repressed by raising the medium phosphate level from 0.33 to 3.3 mM. The enzyme is inhibited by arsenate, inorganic ortho- and pyrophosphate and by a range of organic phosphate-containing compounds, including 2'-AMP, which is an activator of several bacterial transhydrogenases.", "contents": "Transhydrogenase activity in the marine bacterium Beneckea natriegens. The marine bacterium, Beneckea natriegens, which has previously been reported not to form transhydrogenase, has been shown to synthesize a soluble energy-independent transhydrogenase (NADPH:NADP+ oxidoreductase, EC 1.6.1.1), though no energy-linked activity could be detected. The transhydrogenase is induced maximally in stationary phase cells and its formation is 70-90% repressed by raising the medium phosphate level from 0.33 to 3.3 mM. The enzyme is inhibited by arsenate, inorganic ortho- and pyrophosphate and by a range of organic phosphate-containing compounds, including 2'-AMP, which is an activator of several bacterial transhydrogenases."}
{"id": "PMID:12830", "title": "Reactions of the Neurospora crassa nitrate reductase with NAD(P) analogs.", "content": "The assimilatory NADPH-nitrate reductase (NADPH:nitrate oxidoreductase, EC 1.6.6.3) from Neurospora crassa is competitively inhibited by 3-aminopyridine adenine dinucleotide (AAD) and 3-aminopyridine adenine dinucleotide phosphate (AADP) which are structural analogs of NAD and NADP, respectively. The amino group of the pyridine ring of AAD(P) can react with nitrous acid to yield the diazonium derivative which may covalently bind at the NAD(P) site. As a result of covalent attachment, diazotized AAD(P) causes time-dependent irreversible inactivation of nitrate reductase. However, only the NADPH-dependent activities of the nitrate reductase, i.e. the overall NADPH-nitrate reductase and the NADPH-cytochrome c reductase activities, are inactivated. The reduced methyl viologen- and reduced FAD-nitrate reductase activities which do not utilize NADPH are not inhibited. This inactivation by diazotized AADP is prevented by 1 mM NADP. The inclusion of 1 muM FAD can also prevent inactivation, but the FAD effect differs from the NADP protection in that even after removal of the exogenous FAD by extensive dialysis or Sephadex G-25 filtration chromatography, the enzyme is still protected against inactivation. The FAD-generated protected form of nitrate reductase could again be inactivated if the enzyme was treated with NADPH, dialyzed to remove the NADPH, and then exposed to diazotized AADP. When NADP was substituted for NADPH in this experiment, the enzyme remained in the FAD-protected state. Difference spectra of the inactivated nitrate reductase demonstrated the presence of bound AADP, and titration of the sulfhydryl groups of the inactivated enzyme revealed that a loss of accessible sulfhydryls had occurred. The hypothesis generated by these experiments is that diazotized AADP binds at the NADPH site on nitrate reductase and reacts with a functional sulfhydryl at the site. FAD protects the enzyme against inactivation by modifying the sulfhydryl. Since NADPH reverses this protection, it appears the modifications occurring are oxidation-reduction reactions. On the basis of these results, the physiological electron flow in the nitrate reductase is postulated to be from NADPH via sulfhydryls to FAD and then the remainder of the electron carriers as follows: NADPH leads to -SH leads to FAD leads to cytochrome b-557 leads to Mo leads to NO-3.", "contents": "Reactions of the Neurospora crassa nitrate reductase with NAD(P) analogs. The assimilatory NADPH-nitrate reductase (NADPH:nitrate oxidoreductase, EC 1.6.6.3) from Neurospora crassa is competitively inhibited by 3-aminopyridine adenine dinucleotide (AAD) and 3-aminopyridine adenine dinucleotide phosphate (AADP) which are structural analogs of NAD and NADP, respectively. The amino group of the pyridine ring of AAD(P) can react with nitrous acid to yield the diazonium derivative which may covalently bind at the NAD(P) site. As a result of covalent attachment, diazotized AAD(P) causes time-dependent irreversible inactivation of nitrate reductase. However, only the NADPH-dependent activities of the nitrate reductase, i.e. the overall NADPH-nitrate reductase and the NADPH-cytochrome c reductase activities, are inactivated. The reduced methyl viologen- and reduced FAD-nitrate reductase activities which do not utilize NADPH are not inhibited. This inactivation by diazotized AADP is prevented by 1 mM NADP. The inclusion of 1 muM FAD can also prevent inactivation, but the FAD effect differs from the NADP protection in that even after removal of the exogenous FAD by extensive dialysis or Sephadex G-25 filtration chromatography, the enzyme is still protected against inactivation. The FAD-generated protected form of nitrate reductase could again be inactivated if the enzyme was treated with NADPH, dialyzed to remove the NADPH, and then exposed to diazotized AADP. When NADP was substituted for NADPH in this experiment, the enzyme remained in the FAD-protected state. Difference spectra of the inactivated nitrate reductase demonstrated the presence of bound AADP, and titration of the sulfhydryl groups of the inactivated enzyme revealed that a loss of accessible sulfhydryls had occurred. The hypothesis generated by these experiments is that diazotized AADP binds at the NADPH site on nitrate reductase and reacts with a functional sulfhydryl at the site. FAD protects the enzyme against inactivation by modifying the sulfhydryl. Since NADPH reverses this protection, it appears the modifications occurring are oxidation-reduction reactions. On the basis of these results, the physiological electron flow in the nitrate reductase is postulated to be from NADPH via sulfhydryls to FAD and then the remainder of the electron carriers as follows: NADPH leads to -SH leads to FAD leads to cytochrome b-557 leads to Mo leads to NO-3."}
{"id": "PMID:12831", "title": "Purification and characterization of cholesterol esterase from porcine pancreas.", "content": "A protein catalyzing the hydrolysis of cholesterol esters and p-nitrophenyl acetate has been purified 200-fold from porcine pancreas. The enzyme is homogenous as judged by polyacrylamide gel electrophoresis and exhibits a molecular weight of 80 000 as determined by sodium dodecyl sulfate electrophoresis and gel filtration. Activity toward p-nitrophenylacetate exhibits a broad pH optimum and is influenced by a group with a pKa of 5.5--6.0. The enzyme is completely inhibited by diisopropylfluorophosphate at concentrations as low as 10(-5) M, suggesting that it is a serine esterase. Partial inhibition was observed with p-chloromercuribenzoate.", "contents": "Purification and characterization of cholesterol esterase from porcine pancreas. A protein catalyzing the hydrolysis of cholesterol esters and p-nitrophenyl acetate has been purified 200-fold from porcine pancreas. The enzyme is homogenous as judged by polyacrylamide gel electrophoresis and exhibits a molecular weight of 80 000 as determined by sodium dodecyl sulfate electrophoresis and gel filtration. Activity toward p-nitrophenylacetate exhibits a broad pH optimum and is influenced by a group with a pKa of 5.5--6.0. The enzyme is completely inhibited by diisopropylfluorophosphate at concentrations as low as 10(-5) M, suggesting that it is a serine esterase. Partial inhibition was observed with p-chloromercuribenzoate."}
{"id": "PMID:12832", "title": "Conversion of 9-D- and 13-L-hydroperoxylinoleic acids by soybean lipoxygenase-1 under anaerobic conditions.", "content": "Soybean lipoxygenase-1 reacts with both 9-D and 13-L-hydroperoxylinoleic acids under anaerobic conditions. Approximately 40% of the hydroperoxide is converted into oxodienes, absorbing at 285 nm. Concomitantly, more polar compounds are formed, tentatively identified as being mainly epoxy-hydroxy-octadecenoic acids. When oxygen is present, the reaction is strongly inhibited, until in a very slow reaction the oxygen has been depleted. This accounts for the occurrence of a lag period.", "contents": "Conversion of 9-D- and 13-L-hydroperoxylinoleic acids by soybean lipoxygenase-1 under anaerobic conditions. Soybean lipoxygenase-1 reacts with both 9-D and 13-L-hydroperoxylinoleic acids under anaerobic conditions. Approximately 40% of the hydroperoxide is converted into oxodienes, absorbing at 285 nm. Concomitantly, more polar compounds are formed, tentatively identified as being mainly epoxy-hydroxy-octadecenoic acids. When oxygen is present, the reaction is strongly inhibited, until in a very slow reaction the oxygen has been depleted. This accounts for the occurrence of a lag period."}
{"id": "PMID:12833", "title": "Kinetic study of lipoxygenase-hydroperoxylinoleic acid interaction.", "content": "Interaction of lipoxygenase with hydroperoxylinoleic acid, which is the product of this enzyme reaction and acts as an activator, was studied kinetically by the fluorescence stopped-flow method. The kinetic features are consistent with a two-step mechanism involving a fast bimolecular association process followed by a slow unimolecular process. The dissociation constant of the bimolecular process was 3 (+/-2) - 10(-5) M, which was appreciably dependent on temperature and pH, in contrast to the rate constant of the latter process. The enthalpy and the entropy of activation for the unimolecular process were estimated to be 21 kcal/mol and 20 e.u., respectively. The pH dependence of the rate constant indicated that an ionizable group with pK of about 8.6 is involved in the interaction. Linoleic acid, the substrate of lipoxygenase, and oleic acid inhibited the interaction between the lipoxygenase and the hydroperoxylinoleic acid by reducing the rate. A series of saturated monohydric alcohols also reduced the rate of the interaction as the chain length of the alcohols increases, though methanol and ethanol increased the rate of the interaction.", "contents": "Kinetic study of lipoxygenase-hydroperoxylinoleic acid interaction. Interaction of lipoxygenase with hydroperoxylinoleic acid, which is the product of this enzyme reaction and acts as an activator, was studied kinetically by the fluorescence stopped-flow method. The kinetic features are consistent with a two-step mechanism involving a fast bimolecular association process followed by a slow unimolecular process. The dissociation constant of the bimolecular process was 3 (+/-2) - 10(-5) M, which was appreciably dependent on temperature and pH, in contrast to the rate constant of the latter process. The enthalpy and the entropy of activation for the unimolecular process were estimated to be 21 kcal/mol and 20 e.u., respectively. The pH dependence of the rate constant indicated that an ionizable group with pK of about 8.6 is involved in the interaction. Linoleic acid, the substrate of lipoxygenase, and oleic acid inhibited the interaction between the lipoxygenase and the hydroperoxylinoleic acid by reducing the rate. A series of saturated monohydric alcohols also reduced the rate of the interaction as the chain length of the alcohols increases, though methanol and ethanol increased the rate of the interaction."}
{"id": "PMID:12834", "title": "Studies on the metabolism of beta-carotene and apo-beta-carotenoids in rats and chickens.", "content": "(1)The relative abilities of the various fractions of rat and chicken liver to oxidize and reduce retinal and 8'-and 12'-apo-beta-carotenal were investigatjed and it has been shown that, while retinal is exclusely oxidized by the soluble fraction, the apocarotenals are mostly oxidized by the particulate fractions of the homogenate. (2) Addition of NAD+ or NADP+ markedly activated the oxidation of the apocarotenals, but not of retinal by the particulate fractions. (3) Considerable amounts of retinal and 8'-, 10'- and 12'-apo-beta-carotenal were isolated from the intestine of chickens fed beta-carotene and these apocarotenoids were conclusively identified. (4) Significant amounts of 8'-, 10'- and 12'-apo-beta-carotenoic acids were  isolated from the intestine of rats given 8'-apo-beta-carotenal and these apocarotenoic acids were also conclusively identified. (5) In the light of these observations it is suggested that during conversion to vitamin A, the beta-carotene molecule is simultaneously attacked by the dioxygenase at several double bonds, the primary attack being at the central double bond and a tentative scheme for the mechanism of conversion is proposed.", "contents": "Studies on the metabolism of beta-carotene and apo-beta-carotenoids in rats and chickens. (1)The relative abilities of the various fractions of rat and chicken liver to oxidize and reduce retinal and 8'-and 12'-apo-beta-carotenal were investigatjed and it has been shown that, while retinal is exclusely oxidized by the soluble fraction, the apocarotenals are mostly oxidized by the particulate fractions of the homogenate. (2) Addition of NAD+ or NADP+ markedly activated the oxidation of the apocarotenals, but not of retinal by the particulate fractions. (3) Considerable amounts of retinal and 8'-, 10'- and 12'-apo-beta-carotenal were isolated from the intestine of chickens fed beta-carotene and these apocarotenoids were conclusively identified. (4) Significant amounts of 8'-, 10'- and 12'-apo-beta-carotenoic acids were  isolated from the intestine of rats given 8'-apo-beta-carotenal and these apocarotenoic acids were also conclusively identified. (5) In the light of these observations it is suggested that during conversion to vitamin A, the beta-carotene molecule is simultaneously attacked by the dioxygenase at several double bonds, the primary attack being at the central double bond and a tentative scheme for the mechanism of conversion is proposed."}
{"id": "PMID:12835", "title": "Very low density lipoprotein. Dissociation of apolipoprotein C during lipoprotein lipase induced lipolysis.", "content": "The fate of apo C in rat plasma very low density lipoprotein (VLDL) during lipolysis was studied using VLDL labeled specifically with 125I-labeled apo C and purified bovine milk lipoprotein lipase. Incubations were carried out in vitro and included serum-containing systems and albumin containing systems. Free fatty acids generation proceeded with time of incubation in the two systems. It, however, was enhanced 1.5--2 fold by the presence of serum. 125I-labeled apo C equilibrated between very low and high density lipoprotein (HDL) in both systems even when enzyme was not present in the incubation medium, or when the incubation was carried out at 0 degrees C. Upon initiation of lipolysis, more 125I-labeled apo C was transferred to HDL and the transfer was proportional to the magnitude of free fatty acids release. 125I-labeled apo C was also progressively removed from VLDL in the albumin-containing system, although no known lipoprotein acceptor to apo C was present in the medium. The 125I-labeled apo C was recovered predominantly with the medium fraction of d greater than 1.21 g/ml (60--70%), and to a lesser degree with that of d= 1.019--1.21 g/ml. However, the relationship between lipolysis (measured as free fatty acids release) and removal of 125I-labeled apo C from VLDL were indistinguinshable in the albumin containing system and the serum containing system. On the basis of these observations, it is postulated that the removal of apo C during lipolysis of VLDL reflects the nature of the partially degraded VLDL particles, and is independent of the presence of a lipoprotein acceptor to apo C.", "contents": "Very low density lipoprotein. Dissociation of apolipoprotein C during lipoprotein lipase induced lipolysis. The fate of apo C in rat plasma very low density lipoprotein (VLDL) during lipolysis was studied using VLDL labeled specifically with 125I-labeled apo C and purified bovine milk lipoprotein lipase. Incubations were carried out in vitro and included serum-containing systems and albumin containing systems. Free fatty acids generation proceeded with time of incubation in the two systems. It, however, was enhanced 1.5--2 fold by the presence of serum. 125I-labeled apo C equilibrated between very low and high density lipoprotein (HDL) in both systems even when enzyme was not present in the incubation medium, or when the incubation was carried out at 0 degrees C. Upon initiation of lipolysis, more 125I-labeled apo C was transferred to HDL and the transfer was proportional to the magnitude of free fatty acids release. 125I-labeled apo C was also progressively removed from VLDL in the albumin-containing system, although no known lipoprotein acceptor to apo C was present in the medium. The 125I-labeled apo C was recovered predominantly with the medium fraction of d greater than 1.21 g/ml (60--70%), and to a lesser degree with that of d= 1.019--1.21 g/ml. However, the relationship between lipolysis (measured as free fatty acids release) and removal of 125I-labeled apo C from VLDL were indistinguinshable in the albumin containing system and the serum containing system. On the basis of these observations, it is postulated that the removal of apo C during lipolysis of VLDL reflects the nature of the partially degraded VLDL particles, and is independent of the presence of a lipoprotein acceptor to apo C."}
{"id": "PMID:12836", "title": "Studies on the biosynthesis of acylphosphatidylglycerol in Escherichia coli B and B/r.", "content": "The present study has demonstrated that one molecule of acylphosphatidylglycerol was synthesized from two molecules of phosphatidylgycerol by the transacylation reaction in which phosphatidylglycerol acted both as an acyl donor and an acceptor. Phosphatidylethanolamine was identified as an another acyl donor, participating in acylphosphatidylglycerol formation. These results are discussed in terms of a new pathway for the turnover of phosphatidylglycerol in Escherichia coli.", "contents": "Studies on the biosynthesis of acylphosphatidylglycerol in Escherichia coli B and B/r. The present study has demonstrated that one molecule of acylphosphatidylglycerol was synthesized from two molecules of phosphatidylgycerol by the transacylation reaction in which phosphatidylglycerol acted both as an acyl donor and an acceptor. Phosphatidylethanolamine was identified as an another acyl donor, participating in acylphosphatidylglycerol formation. These results are discussed in terms of a new pathway for the turnover of phosphatidylglycerol in Escherichia coli."}
{"id": "PMID:12837", "title": "Inhibition of in vitro cholesterol synthesis by fatty acids.", "content": "Inhibitory effect of 44 species of fatty acids on cholesterol synthesis has been examined with a rat liver enzyme system. In the case of saturated fatty acids, the inhibitory activity increased with chain length to a maximum at 11 to 14 carbons, after which activity decreased rapidly. The inhibition increased with the degree of unsaturation of fatty acids. Introduction of a hydroxy group at the alpha-position of fatty acids abolished the inhibition, while the inhibition was enhanced by the presence of a hydroxy group located in an intermediate position of the chain. Branched chain fatty acids having a methyl group at the terminal showed much higher activity than the corresponding saturated straight chain fatty acids with the same number of carbons. With respect to the mechanism for inhibition, tridecanoate was found to inhibit acetoacetyl-CoA thiolase specifically without affecting the other reaction steps in the cholesterol synthetic pathway. The highly unsaturated fatty acids, arachidonate and linoleate, were specific inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA synthase. On the other hand, ricinoleate (hydroxy acid) and phytanate (branched-chain acid) diminished the conversion of mevalonate to sterols by inhibiting a step or steps between squalene and lanosterol.", "contents": "Inhibition of in vitro cholesterol synthesis by fatty acids. Inhibitory effect of 44 species of fatty acids on cholesterol synthesis has been examined with a rat liver enzyme system. In the case of saturated fatty acids, the inhibitory activity increased with chain length to a maximum at 11 to 14 carbons, after which activity decreased rapidly. The inhibition increased with the degree of unsaturation of fatty acids. Introduction of a hydroxy group at the alpha-position of fatty acids abolished the inhibition, while the inhibition was enhanced by the presence of a hydroxy group located in an intermediate position of the chain. Branched chain fatty acids having a methyl group at the terminal showed much higher activity than the corresponding saturated straight chain fatty acids with the same number of carbons. With respect to the mechanism for inhibition, tridecanoate was found to inhibit acetoacetyl-CoA thiolase specifically without affecting the other reaction steps in the cholesterol synthetic pathway. The highly unsaturated fatty acids, arachidonate and linoleate, were specific inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA synthase. On the other hand, ricinoleate (hydroxy acid) and phytanate (branched-chain acid) diminished the conversion of mevalonate to sterols by inhibiting a step or steps between squalene and lanosterol."}
{"id": "PMID:12839", "title": "Purification and properties of acid phosphatases isolated from Owenia fusiformis.", "content": "Acid phosphatase (EC. 3.1.3.2) has been separated by molecular sieving into two fractions and these fractions were purified by Sephadex ion-exchange chromatography. One of the purified enzymes (fraction II) was purified 830 fold and had a specific activity of 34 international units per mg protein at 37 degrees C and at a pH of 4.9. The Km value with p-nitrophenylphosphate as substrate was 9.10(-4) M and the kinetic studies showed no possibilities of control by allosteric transitions, and no effect of metabolites (amino acids) on the reaction velocity.", "contents": "Purification and properties of acid phosphatases isolated from Owenia fusiformis. Acid phosphatase (EC. 3.1.3.2) has been separated by molecular sieving into two fractions and these fractions were purified by Sephadex ion-exchange chromatography. One of the purified enzymes (fraction II) was purified 830 fold and had a specific activity of 34 international units per mg protein at 37 degrees C and at a pH of 4.9. The Km value with p-nitrophenylphosphate as substrate was 9.10(-4) M and the kinetic studies showed no possibilities of control by allosteric transitions, and no effect of metabolites (amino acids) on the reaction velocity."}
{"id": "PMID:12838", "title": "[Biphasic nature of the light-dependent transport of C14-alanine into Halobacterium holobium cells].", "content": "Biphase character of photoinduced pH change in H. halobium R1 suspension cells is shown: in the first illumination period pH rises and only afterwards it decreases. pH increase is accompanied by the introduction of C14-alanine into the cells, while the decrease by its yield up to the level lower than the \"dark\" one (\"negative\" photoeffect). The bi-phase character of transport processes seems to be explained by the reversible character of light-dependent bacteriorodopsin proton pump in H. halobium R1 cells.", "contents": "[Biphasic nature of the light-dependent transport of C14-alanine into Halobacterium holobium cells]. Biphase character of photoinduced pH change in H. halobium R1 suspension cells is shown: in the first illumination period pH rises and only afterwards it decreases. pH increase is accompanied by the introduction of C14-alanine into the cells, while the decrease by its yield up to the level lower than the \"dark\" one (\"negative\" photoeffect). The bi-phase character of transport processes seems to be explained by the reversible character of light-dependent bacteriorodopsin proton pump in H. halobium R1 cells."}
{"id": "PMID:12845", "title": "Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.", "content": "Factors affecting the coagulant activity of two different prothrombin complex concentrates have been investigated using a sensitive in vitro assay developed in this laboratory. One concentrate contained substantial amounts of potentially thrombogenic material, while the other, which was deliberately fortified with antithrombin III and heparin during production, was judged to be relatively nonthrombogenic. The coagulant activity of the thrombogenic concentrate has been partially identified and was due largely to the presence of coagulation factos IXa and Xa. Neither concentrate contained detectable thrombin. However, after incubation with calcium or various polyamines, large amounts of additional coagulant material, including thrombin, appeared. Heparin and antithrombin III not only neutralized the thrombogenic materials present in the thrombogenic concentrate, but also inhibited the de novo generation of coagulant enzymes during incubation with calcium. The implication of these studies on the preparation of prothrombin complex concentrates and on host susceptibility to thrombosis during the clinical use of these concentrates is discussed.", "contents": "Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo. Factors affecting the coagulant activity of two different prothrombin complex concentrates have been investigated using a sensitive in vitro assay developed in this laboratory. One concentrate contained substantial amounts of potentially thrombogenic material, while the other, which was deliberately fortified with antithrombin III and heparin during production, was judged to be relatively nonthrombogenic. The coagulant activity of the thrombogenic concentrate has been partially identified and was due largely to the presence of coagulation factos IXa and Xa. Neither concentrate contained detectable thrombin. However, after incubation with calcium or various polyamines, large amounts of additional coagulant material, including thrombin, appeared. Heparin and antithrombin III not only neutralized the thrombogenic materials present in the thrombogenic concentrate, but also inhibited the de novo generation of coagulant enzymes during incubation with calcium. The implication of these studies on the preparation of prothrombin complex concentrates and on host susceptibility to thrombosis during the clinical use of these concentrates is discussed."}
{"id": "PMID:12846", "title": "G-6-PD Long Prairie: a new glucose-6-phosphate dehydrogenase mutant exhibiting normal sensitivity to inhibition by NADPH and accompanied by nonspherocytic hemolytic anemia.", "content": "The enzymatic properties of a new glucose-6-phosphate dehydrogenase (G-6-PD) variant (G-6-PD Long Prairie) were studied in a white patient with chronic nonspherocytic hemolysis. The red cells were found to have 2.3%-7.7% normal enzymatic activity. The mutant enzyme exhibited marked heat instability, an increased pH optimum, a moderately decreased Km for G-6-P, and increased utilization of 2-deoxyglucose-6-phosphate and deamino NADP. The Km for NADP and Ki for NADPH were both normal. G-6-PD Long Prairie is an interesting new G-6-PD variant that demonstrates that chronic hemolysis can be associated with modestly decreased G-6-PD activity despite normal sensitivity to inhibition by NADPH. Although increased sensitivity to inhibition by NADPH has been postulated to decrease intracellular enzyme activity, resulting in enhanced susceptibility to hemolysis in certain G-6-PD variants with only moderately decreased enzymatic activity, an alternative mechanism of hemolysis, possibly enzyme thermolability, exists in G-6-PD Long Prairie.", "contents": "G-6-PD Long Prairie: a new glucose-6-phosphate dehydrogenase mutant exhibiting normal sensitivity to inhibition by NADPH and accompanied by nonspherocytic hemolytic anemia. The enzymatic properties of a new glucose-6-phosphate dehydrogenase (G-6-PD) variant (G-6-PD Long Prairie) were studied in a white patient with chronic nonspherocytic hemolysis. The red cells were found to have 2.3%-7.7% normal enzymatic activity. The mutant enzyme exhibited marked heat instability, an increased pH optimum, a moderately decreased Km for G-6-P, and increased utilization of 2-deoxyglucose-6-phosphate and deamino NADP. The Km for NADP and Ki for NADPH were both normal. G-6-PD Long Prairie is an interesting new G-6-PD variant that demonstrates that chronic hemolysis can be associated with modestly decreased G-6-PD activity despite normal sensitivity to inhibition by NADPH. Although increased sensitivity to inhibition by NADPH has been postulated to decrease intracellular enzyme activity, resulting in enhanced susceptibility to hemolysis in certain G-6-PD variants with only moderately decreased enzymatic activity, an alternative mechanism of hemolysis, possibly enzyme thermolability, exists in G-6-PD Long Prairie."}
{"id": "PMID:12847", "title": "Experience with incompatible maternal donors for bone marrow transplantation.", "content": "Marrow transplantation in aplastic anemia and leukemia has generally been limited to siblings who have been histocompatible at both the serological (A and B) and lymphocyte determined (D or MLC) loci of the HLA system. We studied three male patients, two with aplastic anemia and one with acute myelogenous leukemia, who received transplants from their histoincompatible mothers. MLC studies between donors and recipients showed varying degrees of stimulation. Definite engraftment occurred in one patient and transient engraftment in another. Engraftment in the third patient could not be evaluated. In the patient with sustained engraftment, there was clinical evidence of severe graft versus host disease (GVHD) however, this was not substantiated by histologic findings. This preliminary study suggests that MLC incompatibility may be more of an indicator of the risk of GVHD than of bone marrow rejection. If more effective control of GVHD can be accomplished, marrow transplantation between MLC-reactive individuals may become feasible.", "contents": "Experience with incompatible maternal donors for bone marrow transplantation. Marrow transplantation in aplastic anemia and leukemia has generally been limited to siblings who have been histocompatible at both the serological (A and B) and lymphocyte determined (D or MLC) loci of the HLA system. We studied three male patients, two with aplastic anemia and one with acute myelogenous leukemia, who received transplants from their histoincompatible mothers. MLC studies between donors and recipients showed varying degrees of stimulation. Definite engraftment occurred in one patient and transient engraftment in another. Engraftment in the third patient could not be evaluated. In the patient with sustained engraftment, there was clinical evidence of severe graft versus host disease (GVHD) however, this was not substantiated by histologic findings. This preliminary study suggests that MLC incompatibility may be more of an indicator of the risk of GVHD than of bone marrow rejection. If more effective control of GVHD can be accomplished, marrow transplantation between MLC-reactive individuals may become feasible."}
{"id": "PMID:12849", "title": "Looking both ways. Presidential address delivered at British Institute of Radiology Annual Congress-9th April 1976.", "content": "The address looks backward over the progress made in the techniques of radiology--both diagnosis and therapy--over the past 30 years and forward to the possibilities which lie ahead. It draws attention to the continuing need for basic research as the source from which practical advances spring, illustrating this from the development of radiosensitizing drugs. Finally, it emphasized the importance of the Institute as an interdisciplinary forum in the present era of rapid technological advance.", "contents": "Looking both ways. Presidential address delivered at British Institute of Radiology Annual Congress-9th April 1976. The address looks backward over the progress made in the techniques of radiology--both diagnosis and therapy--over the past 30 years and forward to the possibilities which lie ahead. It draws attention to the continuing need for basic research as the source from which practical advances spring, illustrating this from the development of radiosensitizing drugs. Finally, it emphasized the importance of the Institute as an interdisciplinary forum in the present era of rapid technological advance."}
{"id": "PMID:12850", "title": "Atenolol, methyldopa, and chlorthalidone in moderate hypertension.", "content": "Combined treatment with low doses of different drugs is widely used for moderate hypertension. The effects of atenolol and methyldopa at two dose levels and in combination at the lower doses were studied in patients with moderate hypertension on continuous treatment with moderate hypertension on continuous treatment with chlorthalidone. The mean reduction in standing blood pressures obtained with atenolol 150 and 300 mg/day was about 27/17 mm Hg and with methyldopa 750 and 1500 mg/day about 28/14 mm Hg. Combined treatment with atenolol 150 mg/day and methyldopa 750 mg/day for four weeks resulted in a reduction of 38/25 mm Hg. No difference was observed between the two doses of methyldopa. The lower dose of atenolol was better than the lower dose of methyldopa in reducing lying and standing diastolic blood pressures. These findings show that in patients on continuous treatment with chlorthalidone the addition of atenolol alone or methyldopa alone or of atenolol and methyldopa in combination is effective in the treatment of moderate hypertension.", "contents": "Atenolol, methyldopa, and chlorthalidone in moderate hypertension. Combined treatment with low doses of different drugs is widely used for moderate hypertension. The effects of atenolol and methyldopa at two dose levels and in combination at the lower doses were studied in patients with moderate hypertension on continuous treatment with moderate hypertension on continuous treatment with chlorthalidone. The mean reduction in standing blood pressures obtained with atenolol 150 and 300 mg/day was about 27/17 mm Hg and with methyldopa 750 and 1500 mg/day about 28/14 mm Hg. Combined treatment with atenolol 150 mg/day and methyldopa 750 mg/day for four weeks resulted in a reduction of 38/25 mm Hg. No difference was observed between the two doses of methyldopa. The lower dose of atenolol was better than the lower dose of methyldopa in reducing lying and standing diastolic blood pressures. These findings show that in patients on continuous treatment with chlorthalidone the addition of atenolol alone or methyldopa alone or of atenolol and methyldopa in combination is effective in the treatment of moderate hypertension."}
{"id": "PMID:12851", "title": "Tetracycline resistance in pneumococci and group A streptococci. Report of an ad-hoc study group on antibiotic resistance.", "content": "In a nationwide survey in the spring of 1975 into the prevalence of tetracycline resistance among pneumoccoci and group A streptococci isolates, 21 laboratories reported the sensitivity of isolates and details of the patients. Altogether 13% of the 1528 pneumococci isolated were resistant to tetracycline, but there were wide geographical variations. Thirty-six per cent of the 1515 streptococci isolated were resistant, and again there was considerable geographical variation. A high level of resistance in one organism did not correlate with a high level in the other. For both organisms resistance was commoner among inpatients and those aged 50 or over. Tetracycline should probably not be the drug of choice in penicillin-sensitive patients with group A streptococcal infections, but geographical variations were so wide that decisions on treatment are best made on the basis of local survey data.", "contents": "Tetracycline resistance in pneumococci and group A streptococci. Report of an ad-hoc study group on antibiotic resistance. In a nationwide survey in the spring of 1975 into the prevalence of tetracycline resistance among pneumoccoci and group A streptococci isolates, 21 laboratories reported the sensitivity of isolates and details of the patients. Altogether 13% of the 1528 pneumococci isolated were resistant to tetracycline, but there were wide geographical variations. Thirty-six per cent of the 1515 streptococci isolated were resistant, and again there was considerable geographical variation. A high level of resistance in one organism did not correlate with a high level in the other. For both organisms resistance was commoner among inpatients and those aged 50 or over. Tetracycline should probably not be the drug of choice in penicillin-sensitive patients with group A streptococcal infections, but geographical variations were so wide that decisions on treatment are best made on the basis of local survey data."}
{"id": "PMID:12856", "title": "GABA and glycine transport in frog CNS: high affinity uptake and potassium-evoked release in vitro.", "content": "Slices of frog cerebrum, optic tectum, medulla and spinal cord rapidly accumulate [3H]GABA and [3H]glycine from the surrounding medium so that after 10 min tissue:medium ratios as high as 113 for GABA (optic tectum) and 18.5 for glycine (medulla) may be achieved. Kinetic analysis revealed two distinct saturable uptake systems for each amino acid in the 4 CNS areas. The high affinity systems (apparent Km: 9-22 muM for GABA; 5-35 muM for glycine) required sodium ions in the medium and were relatively substrate specific. Significant release of [3H]GABA and [3H]glycine, but not of L-[3H]leucine, was evoked by exposure to medium containing potassium ions in a concentration of 40 mM. The process of release was calcium-dependent. The importance of these results with regard to the roles of GABA and glycine as neurotransmitters in both spinal and supraspinal levels of the amphibian neuraxis is discussed.", "contents": "GABA and glycine transport in frog CNS: high affinity uptake and potassium-evoked release in vitro. Slices of frog cerebrum, optic tectum, medulla and spinal cord rapidly accumulate [3H]GABA and [3H]glycine from the surrounding medium so that after 10 min tissue:medium ratios as high as 113 for GABA (optic tectum) and 18.5 for glycine (medulla) may be achieved. Kinetic analysis revealed two distinct saturable uptake systems for each amino acid in the 4 CNS areas. The high affinity systems (apparent Km: 9-22 muM for GABA; 5-35 muM for glycine) required sodium ions in the medium and were relatively substrate specific. Significant release of [3H]GABA and [3H]glycine, but not of L-[3H]leucine, was evoked by exposure to medium containing potassium ions in a concentration of 40 mM. The process of release was calcium-dependent. The importance of these results with regard to the roles of GABA and glycine as neurotransmitters in both spinal and supraspinal levels of the amphibian neuraxis is discussed."}
{"id": "PMID:12857", "title": "Catecholamine turnover alterations in discrete areas of the median eminence of the 4- and 5-day cyclic rat.", "content": "Using quantitative microfluorimetry in combination with tyrosine hydroxylase inhibition (H44/68) the concentration and turnover of noradrenaline (NA) and dopamine (DA) was studied in the subependymal layer (SEL) and the medial (MPZ) and lateral palisade zone (LPZ) of the rat median eminence during the 4- and 5- day vaginal estrous cycle. Significant cyclic variations were only found in SEL and LPZ. The NA turnover in SEL was high on proestrous and low on all other days of the 4-day estrous cycle, whereas in the 5-day estrous cycle the NA turnover in SEL started to increase already on the second day of diestrous to reach a peak in the afternoon of proestrous. At that time also the NA concentrations in SEL were increased, although significantly only in the 5-day cyclic rats. The DA turnover in LPZ was low on proestrous and high on all other days in both 4-and 5-day cyclic rats. Apart from the median eminence cyclic variations in catecholamine metabolism were only found in the medial preoptic area, where NA turnover was high on proestrous and low on estrous-diestrous. The present findings give further support for the existence of a facilitatory noradrenergic and inhibitory dopaminergic mechanism in the control of gonadotrophin release. Furthermore, it is suggested that an acceleration of reticulo-hypothalamic NA turnover precedes the retardation of tubero-infundibular DA turnover found on proestrous and that the time lag between initial NA activation and subsequent DA inactivation is longer in the 5-than in the 4-day estrous cycle.", "contents": "Catecholamine turnover alterations in discrete areas of the median eminence of the 4- and 5-day cyclic rat. Using quantitative microfluorimetry in combination with tyrosine hydroxylase inhibition (H44/68) the concentration and turnover of noradrenaline (NA) and dopamine (DA) was studied in the subependymal layer (SEL) and the medial (MPZ) and lateral palisade zone (LPZ) of the rat median eminence during the 4- and 5- day vaginal estrous cycle. Significant cyclic variations were only found in SEL and LPZ. The NA turnover in SEL was high on proestrous and low on all other days of the 4-day estrous cycle, whereas in the 5-day estrous cycle the NA turnover in SEL started to increase already on the second day of diestrous to reach a peak in the afternoon of proestrous. At that time also the NA concentrations in SEL were increased, although significantly only in the 5-day cyclic rats. The DA turnover in LPZ was low on proestrous and high on all other days in both 4-and 5-day cyclic rats. Apart from the median eminence cyclic variations in catecholamine metabolism were only found in the medial preoptic area, where NA turnover was high on proestrous and low on estrous-diestrous. The present findings give further support for the existence of a facilitatory noradrenergic and inhibitory dopaminergic mechanism in the control of gonadotrophin release. Furthermore, it is suggested that an acceleration of reticulo-hypothalamic NA turnover precedes the retardation of tubero-infundibular DA turnover found on proestrous and that the time lag between initial NA activation and subsequent DA inactivation is longer in the 5-than in the 4-day estrous cycle."}
{"id": "PMID:12862", "title": "Cerebral carbohydrate metabolism during acute carbon monoxide intoxication.", "content": "The cerebral metabolic effects of 2.5, 5, 7.5, 10, 20, 30 and 60 min exposure to 1% CO were studied in lightly anesthetized rats by measurement of cerebral cortical contents of selected glycolytic and citric acid cylce intermediates, as well as tissue energy phosphates. The initial change in the glycolytic sequence occurred at 2.5 min with decreases in tissue glucose and glucose-6-phosphate and increases in fructose-1-6-diphosphate which indicated an activation of phosphofructokinase and hexokinase. The \"crossover\" pattern between glucose-6-phosphate and fructose-1,6-diphosphate was present at 5, 7.5 and 10 min, but not at 20, 30 and 60 min and thus confirmed previous observations that detection of phosphofructokinase activation in acute unifactorial cerebral hypoxia requires tissue study during the early phases of the experimental exposure. The initial activation of phosphofructokinase occurred in the absence of detectable changes in the tissue content of ATP, ADP, AMP or phosphocreatine and therefore suggested that an imbalance of tissue energy homeostasis is not a prerequisite for the activation of glycolysis in CO intoxication. One percent CO resulted in an increasing malate/oxaloacetate ratio at 5 min, followed by a decrease in alpha-ketoglutarate and aspartate at 7.5 min which suggested a shift in the aspartate aminotransferase reaction towards the replenishment of oxaloacetate removed via the malate dehydrogenase reaction. Subsequent increases in alpha-ketoglutarate at 10, 20, 30 and 60 min were associated with increases in alanine, indicating a contributing role for a secondary shift of the alanine aminotransferase reaction in the replenishment of alpha-ketoglutarate. A comparison of the CO induced changes in the glycolytic and citric acid cycle pathways with those seen in acute hypoxemia indicates no basic qualitative differences in the metabolic responses of brain tissue to the two conditions.", "contents": "Cerebral carbohydrate metabolism during acute carbon monoxide intoxication. The cerebral metabolic effects of 2.5, 5, 7.5, 10, 20, 30 and 60 min exposure to 1% CO were studied in lightly anesthetized rats by measurement of cerebral cortical contents of selected glycolytic and citric acid cylce intermediates, as well as tissue energy phosphates. The initial change in the glycolytic sequence occurred at 2.5 min with decreases in tissue glucose and glucose-6-phosphate and increases in fructose-1-6-diphosphate which indicated an activation of phosphofructokinase and hexokinase. The \"crossover\" pattern between glucose-6-phosphate and fructose-1,6-diphosphate was present at 5, 7.5 and 10 min, but not at 20, 30 and 60 min and thus confirmed previous observations that detection of phosphofructokinase activation in acute unifactorial cerebral hypoxia requires tissue study during the early phases of the experimental exposure. The initial activation of phosphofructokinase occurred in the absence of detectable changes in the tissue content of ATP, ADP, AMP or phosphocreatine and therefore suggested that an imbalance of tissue energy homeostasis is not a prerequisite for the activation of glycolysis in CO intoxication. One percent CO resulted in an increasing malate/oxaloacetate ratio at 5 min, followed by a decrease in alpha-ketoglutarate and aspartate at 7.5 min which suggested a shift in the aspartate aminotransferase reaction towards the replenishment of oxaloacetate removed via the malate dehydrogenase reaction. Subsequent increases in alpha-ketoglutarate at 10, 20, 30 and 60 min were associated with increases in alanine, indicating a contributing role for a secondary shift of the alanine aminotransferase reaction in the replenishment of alpha-ketoglutarate. A comparison of the CO induced changes in the glycolytic and citric acid cycle pathways with those seen in acute hypoxemia indicates no basic qualitative differences in the metabolic responses of brain tissue to the two conditions."}
{"id": "PMID:12863", "title": "Isolation and characterization of a bacteriocin produced by Bacillus stearothermophilus strain NU-10.", "content": "Broth-grown cultures of Bacillus stearothermophilus strain NU-10 produce a bacteriocin which exerts lethal activity on other strains of the bacterium. Optimal production occurs during late maximum stationary phase of growth, at neutral pH, and 55-65 degrees C. The bacteriocin can be substantially purified by a combination of precipitations, centrifugations, and gel filtrations. The thermocin is composed of protein and carbohydrate. It is partially destroyed by proteolytic enzymes but is resistant to DNase, RNase, and various chemical treatments. The bacteriocin has a small molecular weight and exhibits considerable thermostability.", "contents": "Isolation and characterization of a bacteriocin produced by Bacillus stearothermophilus strain NU-10. Broth-grown cultures of Bacillus stearothermophilus strain NU-10 produce a bacteriocin which exerts lethal activity on other strains of the bacterium. Optimal production occurs during late maximum stationary phase of growth, at neutral pH, and 55-65 degrees C. The bacteriocin can be substantially purified by a combination of precipitations, centrifugations, and gel filtrations. The thermocin is composed of protein and carbohydrate. It is partially destroyed by proteolytic enzymes but is resistant to DNase, RNase, and various chemical treatments. The bacteriocin has a small molecular weight and exhibits considerable thermostability."}
{"id": "PMID:12864", "title": "A radioimmunoassay method for 1-beta-D-arabinofuranosyluracil using antibodies directed against 1-beta-D-arabinofuranosylcytosine.", "content": "Above pH 7.0 1-beta-D-arabinofuranosyluracil (ara-U) shows marked pH-dependent cross-reactivity with antibodies directed towards 1-beta-D-arabinofuranosylcytosine. Since this peculiar phenomenon has not been observed with other nucleosides and nucleotides thus far tested, it is probably the result of base-catalyzed tautomerism of ara-U to its enolic form which renders it more structurally similar to 1-beta-D-arabinofuranosylcytosine. By performing the radioimmunoassay at both pH 6.2 and 8.6 we could determine 1-beta-D-arabinofuranosylcytosine and ara-U simultaneously. This method for ara-U assay is simple, fairly reliable, and applicable to blood level studies.", "contents": "A radioimmunoassay method for 1-beta-D-arabinofuranosyluracil using antibodies directed against 1-beta-D-arabinofuranosylcytosine. Above pH 7.0 1-beta-D-arabinofuranosyluracil (ara-U) shows marked pH-dependent cross-reactivity with antibodies directed towards 1-beta-D-arabinofuranosylcytosine. Since this peculiar phenomenon has not been observed with other nucleosides and nucleotides thus far tested, it is probably the result of base-catalyzed tautomerism of ara-U to its enolic form which renders it more structurally similar to 1-beta-D-arabinofuranosylcytosine. By performing the radioimmunoassay at both pH 6.2 and 8.6 we could determine 1-beta-D-arabinofuranosylcytosine and ara-U simultaneously. This method for ara-U assay is simple, fairly reliable, and applicable to blood level studies."}
{"id": "PMID:12865", "title": "Dissociation of 5-fluorouracil uptake from intracellular pH in Walker 256 carcinosarcoma.", "content": "The influence of intracellular pH (pHi) upon 5-fluorouracil (5-FU) uptake has been studied in slices of Walker 256 carcinosarcoma and rat liver. Alteration of pHi was achieved by the addition of either glucose alone or together with oxamic acid to the incubation medium. Results indicated that 5-FU uptake by the tumor slices was not dependent upon pHi, but was enhanced by the presence of glucose. Uptake of 5-FU by liver slices appeared to follow a pattern predictable from the pHi and the pK of the drug.", "contents": "Dissociation of 5-fluorouracil uptake from intracellular pH in Walker 256 carcinosarcoma. The influence of intracellular pH (pHi) upon 5-fluorouracil (5-FU) uptake has been studied in slices of Walker 256 carcinosarcoma and rat liver. Alteration of pHi was achieved by the addition of either glucose alone or together with oxamic acid to the incubation medium. Results indicated that 5-FU uptake by the tumor slices was not dependent upon pHi, but was enhanced by the presence of glucose. Uptake of 5-FU by liver slices appeared to follow a pattern predictable from the pHi and the pK of the drug."}
{"id": "PMID:12866", "title": "New sugars from antigenic lipopolysaccharides of bacteria: identification and synthesis of 3-O-[(R)-1-carboxyethyl]-L-rhamnose, an acidic component of Shigella dysenteriae type 5 lipopolysaccharide.", "content": "A new acidic sugar, 3-O-[(R)-1-carboxyethyl]-L-rhamnose (1), has been identified as a constituent of the O-antigenic lipopolysaccharide of Sh. dysenteriae type 5. The structure of 1 has been established by physico-chemical methods and by synthesis. Alkylation of methyl 2,5-di-O-benzyl-alpha-L-rhamnofuranoside (6) with (S)- or (R)-2-chloropropionic acids, followed by removal of the protecting groups, afforded 3-O-[(R)-1-carboxyethyl]-L-rhamnose (9) and 3-O-[(S)-1-carboxyethyl]-L-rhamnose (10), respectively. The properties of 1 coincide with those of 9.", "contents": "New sugars from antigenic lipopolysaccharides of bacteria: identification and synthesis of 3-O-[(R)-1-carboxyethyl]-L-rhamnose, an acidic component of Shigella dysenteriae type 5 lipopolysaccharide. A new acidic sugar, 3-O-[(R)-1-carboxyethyl]-L-rhamnose (1), has been identified as a constituent of the O-antigenic lipopolysaccharide of Sh. dysenteriae type 5. The structure of 1 has been established by physico-chemical methods and by synthesis. Alkylation of methyl 2,5-di-O-benzyl-alpha-L-rhamnofuranoside (6) with (S)- or (R)-2-chloropropionic acids, followed by removal of the protecting groups, afforded 3-O-[(R)-1-carboxyethyl]-L-rhamnose (9) and 3-O-[(S)-1-carboxyethyl]-L-rhamnose (10), respectively. The properties of 1 coincide with those of 9."}
{"id": "PMID:12867", "title": "Analysis of the inotropic: chronotropic selectivity of dobutamine and dopamine in anaethetised dogs and guinea-pig isolated atria.", "content": "The previously reported in vivo inotropic selectivity of dobutamine and dopamine compared with isoprenaline has been demonstrated in anaesthetised bivagotamised open chest dogs. Responses of heart rate, right ventricular tension, left ventricular dP/dtmax, and blood pressure were measured. Compared with isoprenaline, dobutamine and dopamine were 1.8 and 2.4 times more active in increasing cardiac contractility than rate. The inotropic selectivity of dopamine but not that of dobutamine was abolished by pretreatment of dogs with syrosingopine. In guinea-pig isolated atria, isoprenaline, dobutamine, and dopamine were all slightly rate selective although this was less for dopamine. In atria incubated with phenoxybenzamine from guinea-pigs pretreated with reserpine only the dopamine dose-response curves were displaced to the right indicating a considerable indirect sympathomimetic component. The in vivo inotropic selectivity of dopamine could therefore be explained on the basis of this indirect activity being manifested at lower doses in the myocardium where the stores of catecholamines are more abundant than at the sinoatrial node. However, it is concluded that the inotropic selectivity of dobutamine seen in vivo is not due to indirect activity, reflex effects, or to a difference in the beta-adrenoceptors mediating the rate and tension responses of the heart. Possible alternative explanations are discussed.", "contents": "Analysis of the inotropic: chronotropic selectivity of dobutamine and dopamine in anaethetised dogs and guinea-pig isolated atria. The previously reported in vivo inotropic selectivity of dobutamine and dopamine compared with isoprenaline has been demonstrated in anaesthetised bivagotamised open chest dogs. Responses of heart rate, right ventricular tension, left ventricular dP/dtmax, and blood pressure were measured. Compared with isoprenaline, dobutamine and dopamine were 1.8 and 2.4 times more active in increasing cardiac contractility than rate. The inotropic selectivity of dopamine but not that of dobutamine was abolished by pretreatment of dogs with syrosingopine. In guinea-pig isolated atria, isoprenaline, dobutamine, and dopamine were all slightly rate selective although this was less for dopamine. In atria incubated with phenoxybenzamine from guinea-pigs pretreated with reserpine only the dopamine dose-response curves were displaced to the right indicating a considerable indirect sympathomimetic component. The in vivo inotropic selectivity of dopamine could therefore be explained on the basis of this indirect activity being manifested at lower doses in the myocardium where the stores of catecholamines are more abundant than at the sinoatrial node. However, it is concluded that the inotropic selectivity of dobutamine seen in vivo is not due to indirect activity, reflex effects, or to a difference in the beta-adrenoceptors mediating the rate and tension responses of the heart. Possible alternative explanations are discussed."}
{"id": "PMID:12869", "title": "The effect of fixation conditions on the ultrastructural appearance of gastrin cell granules in the rat gastric pyloric antrum.", "content": "The ultrastructural appearance of gastrin cell (G cell) granules was studied after different fixation procedures. When the pH of prefixation was varied there was greater preservation of the electron density of granule cores after acidic (pH 5.0 and 6.0) than after neutral or alkaline (pH 7.0 and 8.0) prefixation. Increasing duration of prefixation at pH 7.3 resulted in progressive loss of electron density of the granule core with swelling and occasional rupture of the limiting membrane. In tissues where most granules had been rendered electron lucent by fixation, those granules remaining dense cored were preferentially located close to the Golgi zone. These findings indicate that the electron density of G cell granules is profoundly affected by conditions of fixation, and that immature granules are more resistant to loss of core density than mature granules. They also suggest that the gastrin granule in vivo, like other polypeptide granules, may have a \"solid\", osmotically inactive core.", "contents": "The effect of fixation conditions on the ultrastructural appearance of gastrin cell granules in the rat gastric pyloric antrum. The ultrastructural appearance of gastrin cell (G cell) granules was studied after different fixation procedures. When the pH of prefixation was varied there was greater preservation of the electron density of granule cores after acidic (pH 5.0 and 6.0) than after neutral or alkaline (pH 7.0 and 8.0) prefixation. Increasing duration of prefixation at pH 7.3 resulted in progressive loss of electron density of the granule core with swelling and occasional rupture of the limiting membrane. In tissues where most granules had been rendered electron lucent by fixation, those granules remaining dense cored were preferentially located close to the Golgi zone. These findings indicate that the electron density of G cell granules is profoundly affected by conditions of fixation, and that immature granules are more resistant to loss of core density than mature granules. They also suggest that the gastrin granule in vivo, like other polypeptide granules, may have a \"solid\", osmotically inactive core."}
{"id": "PMID:12870", "title": "Stable mutants of mammalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis.", "content": "Upon exposure to 0.1 mM N-phosphonacetyl-L-aspartate (PALA), a transition state analog inhibitor of aspartate transcarbamylase, most cells of a simian virus 40 (SV40)-transformed Syrian hamster line are killed within a few days, but resistant mutants form spontaneously with frequency 2-5 X 10(-5) in a stochastic process not dependent upon the presence of the inhibitor. The resistant phenotype is stable for many months in the absence of PALA. Other cell lines also give resistant mutants, but with substantially lower frequencies. Serial selection with PALA at concentrations up to 25 mM has yielded clones with more than 100 times the original aspartate transcarbamylase activity. The activities of carbamyl-P synthetase and dihydroorotase, which co-purify with aspartate transcarbamylase as a three-enzyme complex, increase in parallel with aspartate transcarbamylase activity in each resistant clone tested, but there is no substantial change in the activities of the last three enzymes of the de novo pathway, which are not in this complex. In each of the three resistant clones tested, there is an increase in the number of aspartate transcarbamylase active sites, determined by titration with 3H-PALA, which closely parallels the increase in enzyme activity. In one resistant clone tested, there is no change in the Ki for PALA or the Km for carbamyl-P. The only mechanism detected for achieving resistance to PALA is an increase in the steady state amount of the three enzyme complex.", "contents": "Stable mutants of mammalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis. Upon exposure to 0.1 mM N-phosphonacetyl-L-aspartate (PALA), a transition state analog inhibitor of aspartate transcarbamylase, most cells of a simian virus 40 (SV40)-transformed Syrian hamster line are killed within a few days, but resistant mutants form spontaneously with frequency 2-5 X 10(-5) in a stochastic process not dependent upon the presence of the inhibitor. The resistant phenotype is stable for many months in the absence of PALA. Other cell lines also give resistant mutants, but with substantially lower frequencies. Serial selection with PALA at concentrations up to 25 mM has yielded clones with more than 100 times the original aspartate transcarbamylase activity. The activities of carbamyl-P synthetase and dihydroorotase, which co-purify with aspartate transcarbamylase as a three-enzyme complex, increase in parallel with aspartate transcarbamylase activity in each resistant clone tested, but there is no substantial change in the activities of the last three enzymes of the de novo pathway, which are not in this complex. In each of the three resistant clones tested, there is an increase in the number of aspartate transcarbamylase active sites, determined by titration with 3H-PALA, which closely parallels the increase in enzyme activity. In one resistant clone tested, there is no change in the Ki for PALA or the Km for carbamyl-P. The only mechanism detected for achieving resistance to PALA is an increase in the steady state amount of the three enzyme complex."}
{"id": "PMID:12875", "title": "Interactions of various 19-nor steroids with human placental microsomal cytochrome P-450 (P-450hpm).", "content": "Each of seven 19-nor steroids exhibited the capacity to facilitate the binding of carbon monoxide (CO) to human placental microsomal cytochrome P-450 although quantitative differences were shown to exist. In every case the facilitation was antagonized by androstenedione. 19-Norandrostenedione produced the most pronounced effect followed by 19-nortestosterone, nandrolone decanoate, norethandrolone, norgestrel, norethynodrel and norethindrone in that order. All steroids investigated produced typical type I binding spectra when added to placental microsomes. Scatched plots also indicated binding of each steroid to two sites--a high-affinity, low-capacity binding site and a low-affinity, high-capacity binding site. Correlations between affinity for either site and capacity to facilitate binding of CO to the cytochrome were not observed nor were there good correlations between maximal absorbance differences (approximately390-420 nm) producible and facilitation capacity. It was therefore concluded that no definitive relationships existed between facilitation capacity and qualitative or quantitative aspects of the steroid-binding spectra. The capacity to facilitate CO binding appeared to reside in the absence of a chemical group substituted at the 10 position on molecules of androgenic steroids since all investigated steroids possessing 10-methyl or other 10-substituted groups either had no effect on the CO-binding spectrum or caused a displacement of CO from ferrous heme. In contrast, all steroids studied that lacked a substitution at C-10 (19-nor steroids) produced a facilitating effect on heme-ligand binding.", "contents": "Interactions of various 19-nor steroids with human placental microsomal cytochrome P-450 (P-450hpm). Each of seven 19-nor steroids exhibited the capacity to facilitate the binding of carbon monoxide (CO) to human placental microsomal cytochrome P-450 although quantitative differences were shown to exist. In every case the facilitation was antagonized by androstenedione. 19-Norandrostenedione produced the most pronounced effect followed by 19-nortestosterone, nandrolone decanoate, norethandrolone, norgestrel, norethynodrel and norethindrone in that order. All steroids investigated produced typical type I binding spectra when added to placental microsomes. Scatched plots also indicated binding of each steroid to two sites--a high-affinity, low-capacity binding site and a low-affinity, high-capacity binding site. Correlations between affinity for either site and capacity to facilitate binding of CO to the cytochrome were not observed nor were there good correlations between maximal absorbance differences (approximately390-420 nm) producible and facilitation capacity. It was therefore concluded that no definitive relationships existed between facilitation capacity and qualitative or quantitative aspects of the steroid-binding spectra. The capacity to facilitate CO binding appeared to reside in the absence of a chemical group substituted at the 10 position on molecules of androgenic steroids since all investigated steroids possessing 10-methyl or other 10-substituted groups either had no effect on the CO-binding spectrum or caused a displacement of CO from ferrous heme. In contrast, all steroids studied that lacked a substitution at C-10 (19-nor steroids) produced a facilitating effect on heme-ligand binding."}
{"id": "PMID:12876", "title": "Fatty acids diffusion in lecithin multilayers: hydration and PH effects.", "content": "The diffusion of the sodium salt of monocarboxylic fatty acids, from formate to stearate, has been studied as a function of water content and pH in lecithin--water lamellar phases. Evolution of the diffusion coefficients with increasing chain length reflects the different localizations of fatty acids in the system. From formate to butyrate, which are mainly restricted to the hydrophilic layer of the phase, diffusion rates decrease rapidly. From butyrate to stearate, fatty acids (anchored at the hydrophilic--lipophilic interface) undergo lateral diffusion and then the decrease of D with increasing chain length is much slower. The diffusion of stereate is already comparable to the diffusion of the lecithin molecule itself. The diffusion rates strongly depend upon phase hydration and pH: it is shown that both parameters control the fatty acid ionization. The variations in diffusion rates observed may be ascribed to the fact that, depending upon their state of ionization, fatty acids assume a different localization and therefore experience different interactions in the lamellar system.", "contents": "Fatty acids diffusion in lecithin multilayers: hydration and PH effects. The diffusion of the sodium salt of monocarboxylic fatty acids, from formate to stearate, has been studied as a function of water content and pH in lecithin--water lamellar phases. Evolution of the diffusion coefficients with increasing chain length reflects the different localizations of fatty acids in the system. From formate to butyrate, which are mainly restricted to the hydrophilic layer of the phase, diffusion rates decrease rapidly. From butyrate to stearate, fatty acids (anchored at the hydrophilic--lipophilic interface) undergo lateral diffusion and then the decrease of D with increasing chain length is much slower. The diffusion of stereate is already comparable to the diffusion of the lecithin molecule itself. The diffusion rates strongly depend upon phase hydration and pH: it is shown that both parameters control the fatty acid ionization. The variations in diffusion rates observed may be ascribed to the fact that, depending upon their state of ionization, fatty acids assume a different localization and therefore experience different interactions in the lamellar system."}
{"id": "PMID:12878", "title": "[Hydrochloric acid secretion of fetal rat gastric mucosa].", "content": "In Rat, spontaneous secretion of hydrochloric acid by gastric mucosa takes place before birth. From day 20 of gestation until birth, the pH of gastric content markedly decreases, reaching 3 pH-units in newborns. During this period, Cl- concentration in gastric juice increases, while p-CO2 remains constant.", "contents": "[Hydrochloric acid secretion of fetal rat gastric mucosa]. In Rat, spontaneous secretion of hydrochloric acid by gastric mucosa takes place before birth. From day 20 of gestation until birth, the pH of gastric content markedly decreases, reaching 3 pH-units in newborns. During this period, Cl- concentration in gastric juice increases, while p-CO2 remains constant."}
{"id": "PMID:12879", "title": "[Multiplicity of beta lactamases: a problem of isoenzymes].", "content": "Analytical isoelectric focusing of beta lactamases is a very sensitive and powerful technique which generally shows a number of satellites near the main enzymatic spike. By this technique we studied two bacterial groups known to produce different beta lactamases, but only one by germ. Analytical isoelectric focusing showed that all bacteria from the same group produce the same satellite system which differs only in relative activity.", "contents": "[Multiplicity of beta lactamases: a problem of isoenzymes]. Analytical isoelectric focusing of beta lactamases is a very sensitive and powerful technique which generally shows a number of satellites near the main enzymatic spike. By this technique we studied two bacterial groups known to produce different beta lactamases, but only one by germ. Analytical isoelectric focusing showed that all bacteria from the same group produce the same satellite system which differs only in relative activity."}
{"id": "PMID:12880", "title": "Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects.", "content": "Labetalol was administered to six hypertensive subjects in increasing doses for seven days. A decrease in both supine and standing arterial pressure and heart rate was observed with no change in cardiac output and few side effects. Exercise tolerance was unaltered by the drug, but the heart rate and arterial pressure response to exercise were significantly blunted. The infusion rate of isoproterenol required to produce tachycardia was increased sevenfold by 800 mg/day labetalol and tenfold by 1600 mg/day. More than twice the control dose of phenylephrine was required during labetalol therapy to produce a rise in diastolic arterial pressure reflex tachycardia to amyl nitrite-induced hypotension was attenuated. These studies indingina pectoris.", "contents": "Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects. Labetalol was administered to six hypertensive subjects in increasing doses for seven days. A decrease in both supine and standing arterial pressure and heart rate was observed with no change in cardiac output and few side effects. Exercise tolerance was unaltered by the drug, but the heart rate and arterial pressure response to exercise were significantly blunted. The infusion rate of isoproterenol required to produce tachycardia was increased sevenfold by 800 mg/day labetalol and tenfold by 1600 mg/day. More than twice the control dose of phenylephrine was required during labetalol therapy to produce a rise in diastolic arterial pressure reflex tachycardia to amyl nitrite-induced hypotension was attenuated. These studies indingina pectoris."}
{"id": "PMID:12882", "title": "Gamma-Glutamyltransferase: kinetic properties and assay conditions when gamma-glutamyl-4-nitroanilide and its 3-carboxy derivative are used as donor substrates.", "content": "The kinetics of human serum gamma-glutamyltransferase (EC 2.3.2.2) were investigated, with use of glycylglycine as a gamma-glutamyl acceptor substrate and gamma-glutamyl-4-nitroanilide and its carboxy derivative, gamma-glutamyl-3-carboxy-4-nitroanilide, as donor substrates. The simultaneous occurrence of both gamma-glutamyltransfer and autotransfer was established by descending paper chromatography. Constant-ratio double-reciprocal plots confirm that the enzyme mechanism is nonsequential (ping-pong bi-bi). Inhibition by either donor was not found, and inhibition by glycylglycine was only observed at concentrations above those of clinical interest. Kinetic constants obtained by nonlinear regression analysis of initial velocity data were used to determine reagent substrate concentrations for the assay of this enzyme. An assay with use of 4 mmol of gamma-glutamyl-3-carboxy-4-nitroanilide and 100 mmol of glycylglycine per liter yielded equivalent activities to those by assay with use of 4 mmol of gamma-glutamyl-4-nitroanilide and 40 mmol of glycylglycine per liter. These concentrations of the carboxy donor and glycylglycine are also \"cost optimal\" and present no procedural problems when used.", "contents": "Gamma-Glutamyltransferase: kinetic properties and assay conditions when gamma-glutamyl-4-nitroanilide and its 3-carboxy derivative are used as donor substrates. The kinetics of human serum gamma-glutamyltransferase (EC 2.3.2.2) were investigated, with use of glycylglycine as a gamma-glutamyl acceptor substrate and gamma-glutamyl-4-nitroanilide and its carboxy derivative, gamma-glutamyl-3-carboxy-4-nitroanilide, as donor substrates. The simultaneous occurrence of both gamma-glutamyltransfer and autotransfer was established by descending paper chromatography. Constant-ratio double-reciprocal plots confirm that the enzyme mechanism is nonsequential (ping-pong bi-bi). Inhibition by either donor was not found, and inhibition by glycylglycine was only observed at concentrations above those of clinical interest. Kinetic constants obtained by nonlinear regression analysis of initial velocity data were used to determine reagent substrate concentrations for the assay of this enzyme. An assay with use of 4 mmol of gamma-glutamyl-3-carboxy-4-nitroanilide and 100 mmol of glycylglycine per liter yielded equivalent activities to those by assay with use of 4 mmol of gamma-glutamyl-4-nitroanilide and 40 mmol of glycylglycine per liter. These concentrations of the carboxy donor and glycylglycine are also \"cost optimal\" and present no procedural problems when used."}
{"id": "PMID:12883", "title": "Biochemical characterization of the tartrate-resistant acid phosphatase of human spleen with leukemic reticuloendotheliosis as a pyrophosphatase.", "content": "A tartrate-resistant acid phosphatase was isolated from a human leukemic spleen by freeze-thawing in saline and purified by repeated chromatography on carboxymethyl-cellulose. The purified enzyme has a molecular weight of 64 000. It catalyzes the hydrolysis of inorganic and organic pyrophosphate as well as the phenolic ester of monoorthophosphate, with optimal activity between pH 5 and 6. However, there is no activity toward mono-orthophosphate esters of aliphatic alcohols. The present data have identified its catalytic function as a pyrophosphatase. However, it has properties different from the pyrophosphatase previously observed in normal animal tissues.", "contents": "Biochemical characterization of the tartrate-resistant acid phosphatase of human spleen with leukemic reticuloendotheliosis as a pyrophosphatase. A tartrate-resistant acid phosphatase was isolated from a human leukemic spleen by freeze-thawing in saline and purified by repeated chromatography on carboxymethyl-cellulose. The purified enzyme has a molecular weight of 64 000. It catalyzes the hydrolysis of inorganic and organic pyrophosphate as well as the phenolic ester of monoorthophosphate, with optimal activity between pH 5 and 6. However, there is no activity toward mono-orthophosphate esters of aliphatic alcohols. The present data have identified its catalytic function as a pyrophosphatase. However, it has properties different from the pyrophosphatase previously observed in normal animal tissues."}
{"id": "PMID:12884", "title": "Ultraviolet spectrometry of serum triglycerides by a totally enzymic method adapted to a centrifugal analyzer.", "content": "We described a micromethod for determining serum triglycerides (triacylglycerols) with the centrifugal analyzer. This technique is based on the procedure of Bublitz and Kennedy [J. Biol. Chem. 211, 951 (1954)]. The enzymic hydrolysis requires 10 min at 30 degrees C. Twenty-six serum triglyceride assays can be done in about 30 min. Concentration and absorbance are linearly related up to 5.0 mmol/liter, but higher concentrations can be assayed by changing conditions slightly. Day-to-day reproducibility for the method was satisfactory (CV, 2.7 to 8.4%). Comparison of this method and two other methods for triglycerides, the automated Hantzsch condensation method and a commercial enzymic method (Calbiochem), gave correlation coefficients of 0.976 and 0.990, respectively. Results are unaffected by the presence of endogenous serum ADP, pyruvic acid, phosphatases, or ATPase.", "contents": "Ultraviolet spectrometry of serum triglycerides by a totally enzymic method adapted to a centrifugal analyzer. We described a micromethod for determining serum triglycerides (triacylglycerols) with the centrifugal analyzer. This technique is based on the procedure of Bublitz and Kennedy [J. Biol. Chem. 211, 951 (1954)]. The enzymic hydrolysis requires 10 min at 30 degrees C. Twenty-six serum triglyceride assays can be done in about 30 min. Concentration and absorbance are linearly related up to 5.0 mmol/liter, but higher concentrations can be assayed by changing conditions slightly. Day-to-day reproducibility for the method was satisfactory (CV, 2.7 to 8.4%). Comparison of this method and two other methods for triglycerides, the automated Hantzsch condensation method and a commercial enzymic method (Calbiochem), gave correlation coefficients of 0.976 and 0.990, respectively. Results are unaffected by the presence of endogenous serum ADP, pyruvic acid, phosphatases, or ATPase."}
{"id": "PMID:12885", "title": "Total lactate dehydrogenase and its isoenzymes in serum in the presence of penicillamine and other sulfhydryl compounds.", "content": "Toward delineation of changes in total lactate dehydrogenase (LDH) and in the distribution of LDH isoenzymes as assessed by polyacrylamide disc electrophoresis, we inbucated human and rat sera with various agents, notably sulfhydryl compounds. Although artefacts were apparent when these agents were used without preliminary adjustment of pH, we saw little alteration in total unitage when one or two volumes of serum was mixed with one volume of any of several thiols, especially penicillamine, at an initial concentration of 0.4 mol/liter and pH 7.0-7.5. Under these conditions, penicillamine caused a loss in LDH-5 after incubation for 1 h at 25 degrees C together with small decreases in mobility of the other four isoenzymes toward the anode. A zymosan region appeared below the albumin and tracking dye area. With longer periods of incubation of rat serum with penicillamine or alpha-mercaptosuccinate, a novel band in the zymogram was noted just above the LDH-4 peak. The observations are discussed in terms of allosteric effectors.", "contents": "Total lactate dehydrogenase and its isoenzymes in serum in the presence of penicillamine and other sulfhydryl compounds. Toward delineation of changes in total lactate dehydrogenase (LDH) and in the distribution of LDH isoenzymes as assessed by polyacrylamide disc electrophoresis, we inbucated human and rat sera with various agents, notably sulfhydryl compounds. Although artefacts were apparent when these agents were used without preliminary adjustment of pH, we saw little alteration in total unitage when one or two volumes of serum was mixed with one volume of any of several thiols, especially penicillamine, at an initial concentration of 0.4 mol/liter and pH 7.0-7.5. Under these conditions, penicillamine caused a loss in LDH-5 after incubation for 1 h at 25 degrees C together with small decreases in mobility of the other four isoenzymes toward the anode. A zymosan region appeared below the albumin and tracking dye area. With longer periods of incubation of rat serum with penicillamine or alpha-mercaptosuccinate, a novel band in the zymogram was noted just above the LDH-4 peak. The observations are discussed in terms of allosteric effectors."}
{"id": "PMID:12886", "title": "Simultaneous spectrophotometry of Fe2+ and Cu2+ in serum denatured with guanidine hydrochloride.", "content": "We show how iron and copper ions may be simultaneously measured in 0.2 ml of serum after using guanidine hydrochloride to cause their release from protein. Sensitive reagents for iron (2,4,6-tripyridyl-s-triazine) and copper (disodium 2,9-dimethyl-4,7-diphenyl-1, 10-phenanthroline disulfonate) facilitate such measurement. We eliminated spectral interference between the two metal-ion complexes by selective use of pH. Results compare well with those obtained by accepted methods in which the concentrations of these ions are measured independently.", "contents": "Simultaneous spectrophotometry of Fe2+ and Cu2+ in serum denatured with guanidine hydrochloride. We show how iron and copper ions may be simultaneously measured in 0.2 ml of serum after using guanidine hydrochloride to cause their release from protein. Sensitive reagents for iron (2,4,6-tripyridyl-s-triazine) and copper (disodium 2,9-dimethyl-4,7-diphenyl-1, 10-phenanthroline disulfonate) facilitate such measurement. We eliminated spectral interference between the two metal-ion complexes by selective use of pH. Results compare well with those obtained by accepted methods in which the concentrations of these ions are measured independently."}
{"id": "PMID:12889", "title": "N-Acetyl-beta-glucosaminidase activity in hydatidiform mole.", "content": "The N-acetyl-beta-glucosaminidase activity in hydatidiform mole is two-fold higher than that in full-term placenta. Qualitatively, the enzymes from the two tissues are similar with respect to KM values and pH optima. Both enzymes also contain a new isoenzyme form detectable by polyacrylamide gel electrophoresis. However, the molar enzyme is more susceptible to heat denaturation, presumably due to the presence of a higher level of the heat-labile isoenzyme form A in this tissue. Data are also presented incicating that the placenta is not the source of the N-acetyl-beta-glucosaminidase activity in maternal serum.", "contents": "N-Acetyl-beta-glucosaminidase activity in hydatidiform mole. The N-acetyl-beta-glucosaminidase activity in hydatidiform mole is two-fold higher than that in full-term placenta. Qualitatively, the enzymes from the two tissues are similar with respect to KM values and pH optima. Both enzymes also contain a new isoenzyme form detectable by polyacrylamide gel electrophoresis. However, the molar enzyme is more susceptible to heat denaturation, presumably due to the presence of a higher level of the heat-labile isoenzyme form A in this tissue. Data are also presented incicating that the placenta is not the source of the N-acetyl-beta-glucosaminidase activity in maternal serum."}
{"id": "PMID:12891", "title": "Enzymatic assay of total cholesterol in serum or plasma by amperometric measurement of rate of oxygen depletion following saponification.", "content": "A method for serum or plasma cholesterol assay involving amperometric measurement of the rate of oxygen depletion in the cholesterol oxidase-catalyzed oxidation of cholesterol is described. The hydrolysis of the serum cholesterol esters is accomplished by saponification of 50 mul of sample with 0.2 ml of ethanolic KOH (1.0 mol/1) containing 0.5% Triton X-100 for 5 min at 75 degrees C. The rate of oxygen consumption in a 25-mul aliquot of this is measured with a Clark electrode in a Beckman Glucose Analyzer and the assay takes about one minute after incubation; results are read digitally on the instrument. The analyzer cell contains 1 ml of 1 M phosphate buffer, pH 7.4, with 100 mg sodium cholate/100 ml and 0.1-0.2 U cholesterol oxidase.", "contents": "Enzymatic assay of total cholesterol in serum or plasma by amperometric measurement of rate of oxygen depletion following saponification. A method for serum or plasma cholesterol assay involving amperometric measurement of the rate of oxygen depletion in the cholesterol oxidase-catalyzed oxidation of cholesterol is described. The hydrolysis of the serum cholesterol esters is accomplished by saponification of 50 mul of sample with 0.2 ml of ethanolic KOH (1.0 mol/1) containing 0.5% Triton X-100 for 5 min at 75 degrees C. The rate of oxygen consumption in a 25-mul aliquot of this is measured with a Clark electrode in a Beckman Glucose Analyzer and the assay takes about one minute after incubation; results are read digitally on the instrument. The analyzer cell contains 1 ml of 1 M phosphate buffer, pH 7.4, with 100 mg sodium cholate/100 ml and 0.1-0.2 U cholesterol oxidase."}
{"id": "PMID:12892", "title": "[Rheological properties of human bronchial secretions: demonstration of proline-rich polypeptides and their role (author's transl)].", "content": "Human bronchial secretions were examined for chemical components and rheological properties. Proline-rich polypeptides (PRP) obtained by ultrasonic treatment and by contact with a cationic resin (AG 50WX2) were purified by gel-filtration chromatography and high-voltage electrophoresis. The chemical composition of these components allowed a classification according to their proline, glycine, glutamic acid and lysine contents. Rheological experiments suggest a biological role for the PRP in the fibrillar structure of sputum.", "contents": "[Rheological properties of human bronchial secretions: demonstration of proline-rich polypeptides and their role (author's transl)]. Human bronchial secretions were examined for chemical components and rheological properties. Proline-rich polypeptides (PRP) obtained by ultrasonic treatment and by contact with a cationic resin (AG 50WX2) were purified by gel-filtration chromatography and high-voltage electrophoresis. The chemical composition of these components allowed a classification according to their proline, glycine, glutamic acid and lysine contents. Rheological experiments suggest a biological role for the PRP in the fibrillar structure of sputum."}
{"id": "PMID:12893", "title": "Measurement of estradiol receptors in human breast tumors by polyacrylamide gel electrophoresis.", "content": "1. Specific estradiol receptors in cytosols from human breast tumors were measured by discontinuous polyacrylamide gel electrophoresis. 2. Binding of estradiol to contaminating sex hormone binding globulin was clearly separated from that due to the specific receptor. 3. The amount of estradiol bound by the receptor was linear with respect to the amount of protein added to gel. 4. The estradiol receptor peak of radioactivity showed saturability and specificity characteristic of an intracellular receptor. 5. The results show that polyacrylamide gel electrophoresis can be used to quantitate specific estradiol receptors in the presence of other high affinity binding components.", "contents": "Measurement of estradiol receptors in human breast tumors by polyacrylamide gel electrophoresis. 1. Specific estradiol receptors in cytosols from human breast tumors were measured by discontinuous polyacrylamide gel electrophoresis. 2. Binding of estradiol to contaminating sex hormone binding globulin was clearly separated from that due to the specific receptor. 3. The amount of estradiol bound by the receptor was linear with respect to the amount of protein added to gel. 4. The estradiol receptor peak of radioactivity showed saturability and specificity characteristic of an intracellular receptor. 5. The results show that polyacrylamide gel electrophoresis can be used to quantitate specific estradiol receptors in the presence of other high affinity binding components."}
{"id": "PMID:12894", "title": "Factors influencing lysozyme determinations by the lysoplate method.", "content": "Some factors influencing the lysoplate method have been investigated. The influences of pH, ionic strength and temperature of the gel medium can be explained by considering the influence of these factors upon the diffusion rate rather than upon the enzymatic properties of lysozyme. Salts and proteins present in a sample probably affect the results in a similar way. Although the method has a variation coefficient around 10% and thus an acceptable precision, its accuracy is variable and doubtful. The method could be clinically interesting, by discriminating lysozyme isoenzymes, or by indirectly detecting proteins associated with some disease states.", "contents": "Factors influencing lysozyme determinations by the lysoplate method. Some factors influencing the lysoplate method have been investigated. The influences of pH, ionic strength and temperature of the gel medium can be explained by considering the influence of these factors upon the diffusion rate rather than upon the enzymatic properties of lysozyme. Salts and proteins present in a sample probably affect the results in a similar way. Although the method has a variation coefficient around 10% and thus an acceptable precision, its accuracy is variable and doubtful. The method could be clinically interesting, by discriminating lysozyme isoenzymes, or by indirectly detecting proteins associated with some disease states."}
{"id": "PMID:12895", "title": "Insoluble human plasma protein immunoadsorbents. Large-scale production and storage.", "content": "Methods for producing and preserving large volumes of insoluble immunoadsorbents (for removing unwated antibodies to serum proteins) from surplus blood bank plasma by glutaraldehyde were evaluated by quantitative and qualitative means using radioactive 125I and immunoelectrophoresis, respectively. Some of the factors affecting the desired physical characteristics and antibody-absorbing properties of the imjunoadsorbent studied were: plasma acidification, varying concentrations of glutaraldehyde, addition of small amounts of formalin, storage under varying conditions of temperature, and exposure to preservatives in the wet and lyophilized state for periods up to 2.5 years. The best preservation of antibody-adsorbing properties (under storage conditions) was obtained in the washed state at 4 degrees C, but good preservation was also obtained at room temperature in the presence 10% formalin and in the unwashed state at room temperature in the presence of unreacted glutaraldehyde. Lyophilization destroyed about 70% of an adsorbent's activity.", "contents": "Insoluble human plasma protein immunoadsorbents. Large-scale production and storage. Methods for producing and preserving large volumes of insoluble immunoadsorbents (for removing unwated antibodies to serum proteins) from surplus blood bank plasma by glutaraldehyde were evaluated by quantitative and qualitative means using radioactive 125I and immunoelectrophoresis, respectively. Some of the factors affecting the desired physical characteristics and antibody-absorbing properties of the imjunoadsorbent studied were: plasma acidification, varying concentrations of glutaraldehyde, addition of small amounts of formalin, storage under varying conditions of temperature, and exposure to preservatives in the wet and lyophilized state for periods up to 2.5 years. The best preservation of antibody-adsorbing properties (under storage conditions) was obtained in the washed state at 4 degrees C, but good preservation was also obtained at room temperature in the presence 10% formalin and in the unwashed state at room temperature in the presence of unreacted glutaraldehyde. Lyophilization destroyed about 70% of an adsorbent's activity."}
{"id": "PMID:12896", "title": "Stimulation of growth hormone release by luteinizing hormone-releasing hormone and melanocyte-stimulating hormone-release inhibiting hormone in the hypophysectomized rat bearing an ectopic pituitary.", "content": "Intrajugular administration of LHRH (0-6 and 1-2 mug) in hypophysectomized rats which received renal grafts of anterior pituitary induced a small but significant rise in plasma GH 5 and 10 min post-treatment. LHRH, at the same dose levels, was ineffective in weight-matched intact controls. MIF, at the dose of 1-2 mug, induced a slight GH rise 5 min after treatment in hypophysectomized trasnplanted rats, while it was ineffective in intact controls. Unlike the two hypothalamic peptides, alpha-MSH (0-6 and 1-2 mug) was ineffective as a GH-releaser in both transplanted and intact rats.", "contents": "Stimulation of growth hormone release by luteinizing hormone-releasing hormone and melanocyte-stimulating hormone-release inhibiting hormone in the hypophysectomized rat bearing an ectopic pituitary. Intrajugular administration of LHRH (0-6 and 1-2 mug) in hypophysectomized rats which received renal grafts of anterior pituitary induced a small but significant rise in plasma GH 5 and 10 min post-treatment. LHRH, at the same dose levels, was ineffective in weight-matched intact controls. MIF, at the dose of 1-2 mug, induced a slight GH rise 5 min after treatment in hypophysectomized trasnplanted rats, while it was ineffective in intact controls. Unlike the two hypothalamic peptides, alpha-MSH (0-6 and 1-2 mug) was ineffective as a GH-releaser in both transplanted and intact rats."}
{"id": "PMID:12898", "title": "Studies on the physico-chemical characteristics of polymorph migration stimulator.", "content": "Polymorph migration stimulator is a supernatant factor produced by the interaction between glucocorticosteroids and human blood monocytes in culture. Studies on the physical characteristics of this factor show that it is soluble and stable at high and low temperatures. Its activity is reduced by acid and alkali treatment and destroyed by the proteolytic enzyme protease. Experiments involving dialysis, ultrafiltration and Sephadex G-100 gell filtration indicate that the molecular weight of the polymorph migration stimulator is between 12,000 and 15,000. It is suggested that this factor may mediate the anti-inflammatory effects of glucocorticosteroids on phagocytic cells.", "contents": "Studies on the physico-chemical characteristics of polymorph migration stimulator. Polymorph migration stimulator is a supernatant factor produced by the interaction between glucocorticosteroids and human blood monocytes in culture. Studies on the physical characteristics of this factor show that it is soluble and stable at high and low temperatures. Its activity is reduced by acid and alkali treatment and destroyed by the proteolytic enzyme protease. Experiments involving dialysis, ultrafiltration and Sephadex G-100 gell filtration indicate that the molecular weight of the polymorph migration stimulator is between 12,000 and 15,000. It is suggested that this factor may mediate the anti-inflammatory effects of glucocorticosteroids on phagocytic cells."}
{"id": "PMID:12899", "title": "The immune response in cirrhotic rats. Antigen distribution, humoral immunity, cell-mediated immunity and splenic suppressor cell activity.", "content": "The immunological disturbances occurring as a result of liver disease have been studied in an animal model of cirrhosis. The mononuclear phagocytic cells of the normal liver phagocytose large amounts of antigen irrespective of whether that antigen is injected directly into the portal or into the systemic circulations. The liver therefore acts as a filter 'in series' and 'in parallel' with the spleen and reduces the immunogenicity of antigens entering the organism by either of these routes. In rats with hepatic cirrhosis, there is a reduction in the capacity of the liver to phagocytose the flagellar antigen of Salmonella adelaide. This results in increased stimulation of splenic lymphoid tissue and in an increased antibody response to this thymus-independent antigen. The increased antigenic stimulus to the spleen may also be responsible for the increased suppressor-cell activity which has been demonstrated in these rats, and may be the mechanism of the diminished cell-mediated immune response both in this animal model of cirrhosis and in the human disease state. These studies suggest that many of the immunological disturbances associated with chronic liver disease may be the result of maldistribution of antigen occurring because of impaired hepatic phagocytic capacity.", "contents": "The immune response in cirrhotic rats. Antigen distribution, humoral immunity, cell-mediated immunity and splenic suppressor cell activity. The immunological disturbances occurring as a result of liver disease have been studied in an animal model of cirrhosis. The mononuclear phagocytic cells of the normal liver phagocytose large amounts of antigen irrespective of whether that antigen is injected directly into the portal or into the systemic circulations. The liver therefore acts as a filter 'in series' and 'in parallel' with the spleen and reduces the immunogenicity of antigens entering the organism by either of these routes. In rats with hepatic cirrhosis, there is a reduction in the capacity of the liver to phagocytose the flagellar antigen of Salmonella adelaide. This results in increased stimulation of splenic lymphoid tissue and in an increased antibody response to this thymus-independent antigen. The increased antigenic stimulus to the spleen may also be responsible for the increased suppressor-cell activity which has been demonstrated in these rats, and may be the mechanism of the diminished cell-mediated immune response both in this animal model of cirrhosis and in the human disease state. These studies suggest that many of the immunological disturbances associated with chronic liver disease may be the result of maldistribution of antigen occurring because of impaired hepatic phagocytic capacity."}
{"id": "PMID:12900", "title": "Evaluation of the prison inmate as a subject in drug assessment.", "content": "The reasons for exclusion of prisoners from research studies on drugs were based mostly on a relatively limited group of laboratory parameters which could have been detected using a simple battery of screening tests. The answers to a medical history form added little to the evaluation of either the prisoner or student groups, were probably very unreliable, and could be just as well confined to a few selected questions regarding drug history as a matter of record. Students gave appropriate responses to a mood scale measurement test while prisoners characteristically did not comply. Because of a combination of various institutional and sociological factors, prisoners probably represent a special subgroup of research volunteers whose health status may not be representative of the total \"healthy\" population. They are unlikely to give accurate or reliable responses in testing situations which rely upon reporting of the subjective effects of drugs with regard to tolerance or pharmacologic effect. Studies of investigational drugs where the likelihood of potentiaal risk is significant should be avoided in such populations unless compliance has been assessed adequately.", "contents": "Evaluation of the prison inmate as a subject in drug assessment. The reasons for exclusion of prisoners from research studies on drugs were based mostly on a relatively limited group of laboratory parameters which could have been detected using a simple battery of screening tests. The answers to a medical history form added little to the evaluation of either the prisoner or student groups, were probably very unreliable, and could be just as well confined to a few selected questions regarding drug history as a matter of record. Students gave appropriate responses to a mood scale measurement test while prisoners characteristically did not comply. Because of a combination of various institutional and sociological factors, prisoners probably represent a special subgroup of research volunteers whose health status may not be representative of the total \"healthy\" population. They are unlikely to give accurate or reliable responses in testing situations which rely upon reporting of the subjective effects of drugs with regard to tolerance or pharmacologic effect. Studies of investigational drugs where the likelihood of potentiaal risk is significant should be avoided in such populations unless compliance has been assessed adequately."}
{"id": "PMID:12913", "title": "The intrinsic pKa-values of functional groups in enzymes: improper deductions from the pH-dependence of steady-state parameters.", "content": "The assumptions implicit in the deductions made from the pH-dependence of rate measurements of enzyme-catalyzed reactions are summarized, and the limitations of such determinations are discussed nonalgebraically. The following types of pH-profile are considered (in order of increasing utility): pH-\"activity\" curves at fixed [S] o;pH-dependences of kcat, Km, kcat/Km, and Ki; pH-dependences of kmodification (by specific reagents) and of competitive labeling (by nonspecific reagents); pH-dependences of elementary steps; and the direct observation of a titrating group.", "contents": "The intrinsic pKa-values of functional groups in enzymes: improper deductions from the pH-dependence of steady-state parameters. The assumptions implicit in the deductions made from the pH-dependence of rate measurements of enzyme-catalyzed reactions are summarized, and the limitations of such determinations are discussed nonalgebraically. The following types of pH-profile are considered (in order of increasing utility): pH-\"activity\" curves at fixed [S] o;pH-dependences of kcat, Km, kcat/Km, and Ki; pH-dependences of kmodification (by specific reagents) and of competitive labeling (by nonspecific reagents); pH-dependences of elementary steps; and the direct observation of a titrating group."}
{"id": "PMID:12914", "title": "Interferon: effects on the immune response and the mechanism of activation of the cellular response.", "content": "The discovery of interferon in 1957 by Drs. Isaacs and Lindenmann led to major revisions in the concepts of man's defenses against viral infections. There are at least two types of interferon. Along with their antiviral properties, they have recently been shown to exert a suppressive effect on the humoral and cellular immune response; they affect both B and T lymphocytes. A variety of substances, including virus, polyribonucleotides, and mitogens for T lymphocytes, are good interferon inducers. T lymphocytes seem to be necessary for these inducers to exert their immunosuppressive effects. The immunosuppressive effects of interferon inducers suggests that interferons may be mediators of suppressor T lymphocyte effects. In the virus system, interferon does not exert its antiviral effects by direct action on the virus, but rather derepresses a cell gene that results in the production of an antiviral protein. This antiviral protein is probably the mediator of inhibition of virus replication. This is a complex sequence of events that results in the interaction of interferon with the cell membrane and the resulting production of the antiviral state in the cell. This review will examine the various steps of this involved process.", "contents": "Interferon: effects on the immune response and the mechanism of activation of the cellular response. The discovery of interferon in 1957 by Drs. Isaacs and Lindenmann led to major revisions in the concepts of man's defenses against viral infections. There are at least two types of interferon. Along with their antiviral properties, they have recently been shown to exert a suppressive effect on the humoral and cellular immune response; they affect both B and T lymphocytes. A variety of substances, including virus, polyribonucleotides, and mitogens for T lymphocytes, are good interferon inducers. T lymphocytes seem to be necessary for these inducers to exert their immunosuppressive effects. The immunosuppressive effects of interferon inducers suggests that interferons may be mediators of suppressor T lymphocyte effects. In the virus system, interferon does not exert its antiviral effects by direct action on the virus, but rather derepresses a cell gene that results in the production of an antiviral protein. This antiviral protein is probably the mediator of inhibition of virus replication. This is a complex sequence of events that results in the interaction of interferon with the cell membrane and the resulting production of the antiviral state in the cell. This review will examine the various steps of this involved process."}
{"id": "PMID:12915", "title": "A test of the concept of \"underlying depressive illness\" in the treatment of anxiety states.", "content": "In order to test the validity of the concept of anxiety states masking an underlying depressive illness, patients clinically diagnosed as suffering from anxiety or tension states were treated on a random double-blind basis for 4 weeks with either a pure anxiolytic, lorazepam, or an anxiolytic/antidepressant preparation, fluphenazine with nortriptyline. Patients' self-ratings were very similar to the physicians' ratings which showed that fluphenazine/nortriptyline was associated with significantly greater overall improvement(p less than 0.01), as well as significantly greater improvements in the group of symptoms specifically related to depression(p less than 0.05). These results suggest that a depressive element is present in an appreciable proportion of patients presenting with apparent anxiety states, and antidepressant as well as anxiolytic treatment is required. Patients selected on the basis that they had improved satisfactorily at the end of the 4-weeks' treatment were followed up for a further 3 months without medication, and the relapse rate was 24%, irrespective of previous treatment. More of the patients treated with lorazepam had to be excluded from the follow-up because of failure to improve, and these probably represented the proportion (19%) of this population with an appreciable depressive element to their illness.", "contents": "A test of the concept of \"underlying depressive illness\" in the treatment of anxiety states. In order to test the validity of the concept of anxiety states masking an underlying depressive illness, patients clinically diagnosed as suffering from anxiety or tension states were treated on a random double-blind basis for 4 weeks with either a pure anxiolytic, lorazepam, or an anxiolytic/antidepressant preparation, fluphenazine with nortriptyline. Patients' self-ratings were very similar to the physicians' ratings which showed that fluphenazine/nortriptyline was associated with significantly greater overall improvement(p less than 0.01), as well as significantly greater improvements in the group of symptoms specifically related to depression(p less than 0.05). These results suggest that a depressive element is present in an appreciable proportion of patients presenting with apparent anxiety states, and antidepressant as well as anxiolytic treatment is required. Patients selected on the basis that they had improved satisfactorily at the end of the 4-weeks' treatment were followed up for a further 3 months without medication, and the relapse rate was 24%, irrespective of previous treatment. More of the patients treated with lorazepam had to be excluded from the follow-up because of failure to improve, and these probably represented the proportion (19%) of this population with an appreciable depressive element to their illness."}
{"id": "PMID:12923", "title": "Negative inotropic effect of lidocaine in patients with coronary arterial disease and normal subjects.", "content": "The effect of administration of lidocaine on left ventricular performance was studied using systolic time intervals in nine normal subjects, eight patients with stable angina, and 15 patients with acute myocardial infarction. The greatest response in systolic time intervals occurred at three minutes after intravenous injection of lidocaine (100 mg), with values returning to baseline at 10 to 15 minutes. Administration of lidocaine produced a significant prolongation of the preejection period (PEP) corrected for heart rate in all groups and a prolongation of the ratio of PEP to left ventricular ejection time (PEP/LVET) in patients with angina. The group with acute myocardial infarction exhibited a hyperadrenergic state, as shown by a short baseline QS2I. The QS I was lengthened by administration of lidocaine in all groups, but this was more profound in those with acute myocardial infarction. These changes in systolic time intervals were still present at two hours after injection in six patients with acute myocardial infarction in whom an infusion of lidocaine followed the initial bolus. The effect of administering lidocaine after intravenous injection of propranolol (5 mg) was also studied in six normal subjects. Although propranolol therapy along prolonged the PEP/LVET, a further significant prolongation followed subsequent injection of lidocaine.", "contents": "Negative inotropic effect of lidocaine in patients with coronary arterial disease and normal subjects. The effect of administration of lidocaine on left ventricular performance was studied using systolic time intervals in nine normal subjects, eight patients with stable angina, and 15 patients with acute myocardial infarction. The greatest response in systolic time intervals occurred at three minutes after intravenous injection of lidocaine (100 mg), with values returning to baseline at 10 to 15 minutes. Administration of lidocaine produced a significant prolongation of the preejection period (PEP) corrected for heart rate in all groups and a prolongation of the ratio of PEP to left ventricular ejection time (PEP/LVET) in patients with angina. The group with acute myocardial infarction exhibited a hyperadrenergic state, as shown by a short baseline QS2I. The QS I was lengthened by administration of lidocaine in all groups, but this was more profound in those with acute myocardial infarction. These changes in systolic time intervals were still present at two hours after injection in six patients with acute myocardial infarction in whom an infusion of lidocaine followed the initial bolus. The effect of administering lidocaine after intravenous injection of propranolol (5 mg) was also studied in six normal subjects. Although propranolol therapy along prolonged the PEP/LVET, a further significant prolongation followed subsequent injection of lidocaine."}
{"id": "PMID:12926", "title": "Fosfomycin: Absorption and excretion.", "content": "Summarized results of absorption and excretion of fosfomycin after oral and intravenous administration obtained from hospitals and institutions in Japan are reported. Fosfomycin was rapidly absorbed and excreted from the urine once it was distributed, the 6-hour urinary recovery reaching about 20% in the case of oral administration and 90% in the case of intravenous injection. These phenomena are almost the same as those previously published. Higher concentration was noticed in the kidney, which gradually decreased according to the fall of the blood level. The blood level reached its maximum of about 3 mug/ml after oral administration to adults at a dose of 500 mg.", "contents": "Fosfomycin: Absorption and excretion. Summarized results of absorption and excretion of fosfomycin after oral and intravenous administration obtained from hospitals and institutions in Japan are reported. Fosfomycin was rapidly absorbed and excreted from the urine once it was distributed, the 6-hour urinary recovery reaching about 20% in the case of oral administration and 90% in the case of intravenous injection. These phenomena are almost the same as those previously published. Higher concentration was noticed in the kidney, which gradually decreased according to the fall of the blood level. The blood level reached its maximum of about 3 mug/ml after oral administration to adults at a dose of 500 mg."}
{"id": "PMID:12927", "title": "Fosfomycin in pneumococcal meningitis.", "content": "A study has been made of 12 patients with pneumococcal meningitis with ages ranging from 12 months to 59 years. In all cases pneumococcus was isolated in the cerebrospinal fluid (CSF). Seventeen pneumococci were studied for their sensitivity to fosfomycin, ampicillin and gentamicin, including their MIC. All were sensitive to fosfomycin and ampicillin and 7 to gentamicin. On the other hand there has also been made a study of the interaction between fosfomycin plus ampicillin and fosfomycin plus gentamicin. The concentration of antibiotics in plasma and CSF had been determined. The association of fosfomycin to penicillin or ampicillin was also studied in some cases, depending on whether the patient was younger or older than 2 years, and in other cases, the association of fosfomycin with gentamicin. The concentrations of antibiotics in the CSF varied according to the stage of evolution of the meningitis. As regards clinical results, 10 cures and 2 failures have been obtained. The pneumococcus was eradicated from the CSF in all cases, including the two failures, in the control carried out 2-3 days after beginning of treatment, the rest of the analytical data of the CSF became normal within 5 and 17 days treatment.", "contents": "Fosfomycin in pneumococcal meningitis. A study has been made of 12 patients with pneumococcal meningitis with ages ranging from 12 months to 59 years. In all cases pneumococcus was isolated in the cerebrospinal fluid (CSF). Seventeen pneumococci were studied for their sensitivity to fosfomycin, ampicillin and gentamicin, including their MIC. All were sensitive to fosfomycin and ampicillin and 7 to gentamicin. On the other hand there has also been made a study of the interaction between fosfomycin plus ampicillin and fosfomycin plus gentamicin. The concentration of antibiotics in plasma and CSF had been determined. The association of fosfomycin to penicillin or ampicillin was also studied in some cases, depending on whether the patient was younger or older than 2 years, and in other cases, the association of fosfomycin with gentamicin. The concentrations of antibiotics in the CSF varied according to the stage of evolution of the meningitis. As regards clinical results, 10 cures and 2 failures have been obtained. The pneumococcus was eradicated from the CSF in all cases, including the two failures, in the control carried out 2-3 days after beginning of treatment, the rest of the analytical data of the CSF became normal within 5 and 17 days treatment."}
{"id": "PMID:12928", "title": "Antimicrobial activity of tibezonium (TBZ).", "content": "The activity in vitro of tibezonium (Rec 15-0691), a new 1,5-benzodiazepine derivative, has been investigated. The drug was found active especially against Streptococcus, Diplococcus and Corynebacterium strains which are agents of oropharyngeal diseases. The activity of tibezonium was pH dependent against Staphylococcus aureus SG 511 and Streptococcus pyogenes 821 (at pH 8.0-8.5 It was more active) and the presence of horse serum provoked a small decrease of the antimicrobial properties. No interference on the activity of the tibezonium has been found in presence of smokers and non-smokers saliva.", "contents": "Antimicrobial activity of tibezonium (TBZ). The activity in vitro of tibezonium (Rec 15-0691), a new 1,5-benzodiazepine derivative, has been investigated. The drug was found active especially against Streptococcus, Diplococcus and Corynebacterium strains which are agents of oropharyngeal diseases. The activity of tibezonium was pH dependent against Staphylococcus aureus SG 511 and Streptococcus pyogenes 821 (at pH 8.0-8.5 It was more active) and the presence of horse serum provoked a small decrease of the antimicrobial properties. No interference on the activity of the tibezonium has been found in presence of smokers and non-smokers saliva."}
{"id": "PMID:12930", "title": "Effects of estradiol-17beta on the induction of gonadotropin release by electrical stimulation of the hypothalamus in rhesus monkeys.", "content": "Serum LH and FSH were measured at 60, 30, and 0 min before, at 5, 15, and 30 min during, and at 10, 45, and 90 min after bilateral electrical stimulation (ES) of various hypothalamic regions in 12 unanesthetized ovariectomized rhesus monkeys. ES of the arcuate-ventromedial nuclei (medial basal hypothalamus; MBH) induced a prompt increase in serum LH that persisted throughout stimulation and returned to basal levels within 90 min thereafter. FSH was also released, but the release was slower and less dramatic than that of LH. Sham stimulation (0muA) caused no change in serum gonadotropins. The amount of LH released after MBH-ES depended upon current strength (1.0 mA greater than 0,5 or 0.7 mA). Three sequential 30-min MBH-ES trials at 90-min intervals induced comparable LH responses and 3 h of continuous MBH-ES maintained elevated serum LH levels throughout the stimulation period, suggesting that these stimulation period, suggesting that these stimulation parameters did not completely deplete pituitary stores of releasable LH. The character of the LH response was similar in individual monkeys through 3 to 24 trials during 4 to 18 months. Comparisons were made of the effects of estradiol-17beta (E2) treatment at different doses and for different intervals of time before MBH-ES. ES-induced LH release was not affected by low levels (25 and 55 pg/ml) ofE2 for 48 h, but was reduced by higher E2 concentrations (100 or 230 pg/ml). E2 concentrations of 100 pg/ml had no effect at 24 h, but reduced MBH-ES-activated LH release at 48 to 96 h; the degree of depression was time-related (48 h less than 72 h less than 96 h). ES of the preoptic-suprachiasmatic region (rostral hypothalamus; RH) in non-E2-treated monkeys also released LH, but this increase was less than after MBH-ES. FSH release was not measurable after RH-ES. In contrast to the depressed LH response to MBH-ES after 48 h of E2 (100 pg/ml), the response to RH-ES was not inhibited by this E2 regimen. These data suggest that ES of an area extending caudally from the rostral hypothalamus to the arcurate-median eminence region will evoke LH release in rhesus monkeys. This electrically induced gonadotropin release was affected by administration of physiological levels of E2 but the nature of effect depended on the specific region stimulated: distinct inhibition of the gonadotropic response to MBH-ES and slight facilitation of the response to RH-ES.", "contents": "Effects of estradiol-17beta on the induction of gonadotropin release by electrical stimulation of the hypothalamus in rhesus monkeys. Serum LH and FSH were measured at 60, 30, and 0 min before, at 5, 15, and 30 min during, and at 10, 45, and 90 min after bilateral electrical stimulation (ES) of various hypothalamic regions in 12 unanesthetized ovariectomized rhesus monkeys. ES of the arcuate-ventromedial nuclei (medial basal hypothalamus; MBH) induced a prompt increase in serum LH that persisted throughout stimulation and returned to basal levels within 90 min thereafter. FSH was also released, but the release was slower and less dramatic than that of LH. Sham stimulation (0muA) caused no change in serum gonadotropins. The amount of LH released after MBH-ES depended upon current strength (1.0 mA greater than 0,5 or 0.7 mA). Three sequential 30-min MBH-ES trials at 90-min intervals induced comparable LH responses and 3 h of continuous MBH-ES maintained elevated serum LH levels throughout the stimulation period, suggesting that these stimulation period, suggesting that these stimulation parameters did not completely deplete pituitary stores of releasable LH. The character of the LH response was similar in individual monkeys through 3 to 24 trials during 4 to 18 months. Comparisons were made of the effects of estradiol-17beta (E2) treatment at different doses and for different intervals of time before MBH-ES. ES-induced LH release was not affected by low levels (25 and 55 pg/ml) ofE2 for 48 h, but was reduced by higher E2 concentrations (100 or 230 pg/ml). E2 concentrations of 100 pg/ml had no effect at 24 h, but reduced MBH-ES-activated LH release at 48 to 96 h; the degree of depression was time-related (48 h less than 72 h less than 96 h). ES of the preoptic-suprachiasmatic region (rostral hypothalamus; RH) in non-E2-treated monkeys also released LH, but this increase was less than after MBH-ES. FSH release was not measurable after RH-ES. In contrast to the depressed LH response to MBH-ES after 48 h of E2 (100 pg/ml), the response to RH-ES was not inhibited by this E2 regimen. These data suggest that ES of an area extending caudally from the rostral hypothalamus to the arcurate-median eminence region will evoke LH release in rhesus monkeys. This electrically induced gonadotropin release was affected by administration of physiological levels of E2 but the nature of effect depended on the specific region stimulated: distinct inhibition of the gonadotropic response to MBH-ES and slight facilitation of the response to RH-ES."}
{"id": "PMID:12931", "title": "Gonadotropin secretion in cryptorchid and castrate rams and the acute effects of exogenous steroid treatment.", "content": "Gonadotropin secretion in cryptorchid and castrate rams and the acutve been determined. Rams made cryptorchid at 6 weeks of age had increased serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) when determined at 9 months of age. These levels approached those of the castrate animal; and yet serum levels of testosterone (T) were unchanged. Even though mean serum LH concentrations were elevated sixfold to eightfold over those of intact ram levels, a temporal relationship between this hormone and T was observed similar to that reported in the intact ram. Intramuscular injections of dihydrotestosterone had no effect on circulating levels of LH or FSH in either cryptorchid or castrate rams, whereas T effectively reduced these gonadotropins in castrate but not in cryptorchid rams. Only estradiol-17beta (E2) was effective in both cryptorchid and castrate rams. Estradiol was a potent inhibitor of LH secretion; however, its effect on FSH levels was less dramatic. This suggests that testicular products other than E2 may be important in the regulation of FSH production and/or release. Importantly, the inhibition of LH secretion lasted less than 12 h; whereas, the negative effects of E2 on FSH secretion lasted 72 to 144 h. In conclusion, results from this study show that T is not the single factor responsible for regulation of LH and FSH secretion in male sheep. Estradiol may be an important regulator of gonadotropin secretion, but 5alpha-reduction plays no apparent role in this process.", "contents": "Gonadotropin secretion in cryptorchid and castrate rams and the acute effects of exogenous steroid treatment. Gonadotropin secretion in cryptorchid and castrate rams and the acutve been determined. Rams made cryptorchid at 6 weeks of age had increased serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) when determined at 9 months of age. These levels approached those of the castrate animal; and yet serum levels of testosterone (T) were unchanged. Even though mean serum LH concentrations were elevated sixfold to eightfold over those of intact ram levels, a temporal relationship between this hormone and T was observed similar to that reported in the intact ram. Intramuscular injections of dihydrotestosterone had no effect on circulating levels of LH or FSH in either cryptorchid or castrate rams, whereas T effectively reduced these gonadotropins in castrate but not in cryptorchid rams. Only estradiol-17beta (E2) was effective in both cryptorchid and castrate rams. Estradiol was a potent inhibitor of LH secretion; however, its effect on FSH levels was less dramatic. This suggests that testicular products other than E2 may be important in the regulation of FSH production and/or release. Importantly, the inhibition of LH secretion lasted less than 12 h; whereas, the negative effects of E2 on FSH secretion lasted 72 to 144 h. In conclusion, results from this study show that T is not the single factor responsible for regulation of LH and FSH secretion in male sheep. Estradiol may be an important regulator of gonadotropin secretion, but 5alpha-reduction plays no apparent role in this process."}
{"id": "PMID:12932", "title": "Variants of HTC cells with low tyrosine aminotransferinase inducibility and apparently normal glucorticoid receptors.", "content": "Variants of HTC cells showing little or no induction of tyrosine aminotransferase in response to glucorticoids have been isolated by repeated cloning without deliberate selective pressures. In this paper, the derivation and some properties of these cells, compared with both high-inducing clones and wild-type cells, are described. The non-inducing cells all grew well, and were not induced even by unusually high concentrations of steroid. The enzyme activity had a normal half-life of decay and heat inactivation. It was inactivated by antiserum against authentic tyrosine aminotransferase, and no evidence for antigenically active, enzymatically inactive enzyme was found. No great variability was seen in the few other enzyme activities tested. Glucorticoid receptors were present in all the clones, With respect to concentration, cellular uptake, cell-free binding to nuclei and intracellular localiztion, no differences were found between the receptors of inducible and non-inducible clones. These are the first cells derived from an inducible type to be characterized as having normal receptor while becoming steroid resistant. They appear to be blocked in a late step of the response to the steroid, and therefore may prove useful in analyzing these later steps.", "contents": "Variants of HTC cells with low tyrosine aminotransferinase inducibility and apparently normal glucorticoid receptors. Variants of HTC cells showing little or no induction of tyrosine aminotransferase in response to glucorticoids have been isolated by repeated cloning without deliberate selective pressures. In this paper, the derivation and some properties of these cells, compared with both high-inducing clones and wild-type cells, are described. The non-inducing cells all grew well, and were not induced even by unusually high concentrations of steroid. The enzyme activity had a normal half-life of decay and heat inactivation. It was inactivated by antiserum against authentic tyrosine aminotransferase, and no evidence for antigenically active, enzymatically inactive enzyme was found. No great variability was seen in the few other enzyme activities tested. Glucorticoid receptors were present in all the clones, With respect to concentration, cellular uptake, cell-free binding to nuclei and intracellular localiztion, no differences were found between the receptors of inducible and non-inducible clones. These are the first cells derived from an inducible type to be characterized as having normal receptor while becoming steroid resistant. They appear to be blocked in a late step of the response to the steroid, and therefore may prove useful in analyzing these later steps."}
{"id": "PMID:12933", "title": "Differential effect of hypophysectomy on the synthesis of beta-glucuronidase and other androgen-inducible enzymes in mouse kidney.", "content": "The levels of several androgen responsive enzymes including beta-glucuronidase, alcohol dehydrogenase, D-amino acid oxidase and arginase, were compared in kidneys of normal and hypophysectomized female mice after treatment with testosterone. While hypophysectomy did not alter the basal level of glucuronidase, the androgen-mediated accumulation of kidney beta-glucuronidase was greatly decreased in hypophysectomized mice. Measurements of the rate of synthesis of glucuronidase showed that after androgen treatment the enzyme was synthesized in kidney of hypophysectomized mice at only 5% the normal rate. Glucuronidase activity in seven other organs was not appreciably affected by treatment with androgens or by hypophysectomy. Unlike the effect of hypophysectomy on kidney glucuronidase, there was no reduction in the accumulation of alcohol dehydrogenase or D-amino acid oxidase in kidney of hypophysectomized mice after androgen treatment. Hypophysectomy caused a large reduction in kidney arginase activity. However, subsequent administration of testosterone restored much of this activity. It is concluded that there are at least two mechanisms by which androgens increase enzyme activity in kidney. The normal increase in activity or rate of synthesis of beta-glucuronidase following androgen administration requires pituitary hormones and/or products of these hormones, while the increase in activity of enzymes like alcohol dehydrogenase and D-amino acid oxidase does not require pituitary hormones.", "contents": "Differential effect of hypophysectomy on the synthesis of beta-glucuronidase and other androgen-inducible enzymes in mouse kidney. The levels of several androgen responsive enzymes including beta-glucuronidase, alcohol dehydrogenase, D-amino acid oxidase and arginase, were compared in kidneys of normal and hypophysectomized female mice after treatment with testosterone. While hypophysectomy did not alter the basal level of glucuronidase, the androgen-mediated accumulation of kidney beta-glucuronidase was greatly decreased in hypophysectomized mice. Measurements of the rate of synthesis of glucuronidase showed that after androgen treatment the enzyme was synthesized in kidney of hypophysectomized mice at only 5% the normal rate. Glucuronidase activity in seven other organs was not appreciably affected by treatment with androgens or by hypophysectomy. Unlike the effect of hypophysectomy on kidney glucuronidase, there was no reduction in the accumulation of alcohol dehydrogenase or D-amino acid oxidase in kidney of hypophysectomized mice after androgen treatment. Hypophysectomy caused a large reduction in kidney arginase activity. However, subsequent administration of testosterone restored much of this activity. It is concluded that there are at least two mechanisms by which androgens increase enzyme activity in kidney. The normal increase in activity or rate of synthesis of beta-glucuronidase following androgen administration requires pituitary hormones and/or products of these hormones, while the increase in activity of enzymes like alcohol dehydrogenase and D-amino acid oxidase does not require pituitary hormones."}
{"id": "PMID:12934", "title": "Neonatal treatment with sex steroids: relationship between the uterotropic response and the estrogen \"receptor\" in prepubertal rats.", "content": "We tested the hypothesis that neonatal treatment of rats with testosterone propionate (TP) or estradiol benzoate (EB) reduces the uterine responsiveness to estradiol and reduces the concentration of estrogen \"receptor\" before puberty, and that both of these events precede the onset of the persistent estrus syndrome. Thre-day-old female rats were injected with 100 mug EB, TP or sesame oil (controls) and at 23 and 31 days of age (before the onset of puberty) the uterine cytoplasmic content of specific 8S estradiol-binding protein was measured by sucrose density gradients. Binding by the nuclear fraction was also measured utilizing an exchange assay. In a subgroup of rats also treated neonatally, 2 mug/kg body weight estradiol-17beta was injected at 22 and 30 days of age and uterine wiights were measured as a test for uterine responsiveness. At 23 and 31 days of age the uterine cytoplasmic 8S estrogen \"receptor\" was significantly reduced in the EB-treated rats, but the uterotropic response to estradiol was blocked only in the 23 day old rats; the uterine response at 31 days was slightly, but not significantly, reduced. In contrast, neonatally administered TP had no effect on either the concentration of cytoplasmic estradiol-binding sites or uterine responsiveness. Nuclear binding of estradiol was unaffected by either TP or EB treatment in both age groups. In a futher experiment in rats ovariectomized at 9 days of age, those treated neonatally with EB had significantly smaller uteri than their untreated ovariectomized controls, thus providing indirect evidence for an extravarian factor affected by neonatal treatment. These data support the hypothesis that neonatal EB treatment may directly inhibit the synthesis or replenishment of the 8S estradiol \"receptor\" prior to the development of the persistent estrus syndrome (persistent vaginal estrus, anovulation and polycystic ovaries). A neonatally-induced neuroendocrine disorder affecting steroid secretion by the ovary or adrenal may also exist prepubertally to account for the uterine defects.", "contents": "Neonatal treatment with sex steroids: relationship between the uterotropic response and the estrogen \"receptor\" in prepubertal rats. We tested the hypothesis that neonatal treatment of rats with testosterone propionate (TP) or estradiol benzoate (EB) reduces the uterine responsiveness to estradiol and reduces the concentration of estrogen \"receptor\" before puberty, and that both of these events precede the onset of the persistent estrus syndrome. Thre-day-old female rats were injected with 100 mug EB, TP or sesame oil (controls) and at 23 and 31 days of age (before the onset of puberty) the uterine cytoplasmic content of specific 8S estradiol-binding protein was measured by sucrose density gradients. Binding by the nuclear fraction was also measured utilizing an exchange assay. In a subgroup of rats also treated neonatally, 2 mug/kg body weight estradiol-17beta was injected at 22 and 30 days of age and uterine wiights were measured as a test for uterine responsiveness. At 23 and 31 days of age the uterine cytoplasmic 8S estrogen \"receptor\" was significantly reduced in the EB-treated rats, but the uterotropic response to estradiol was blocked only in the 23 day old rats; the uterine response at 31 days was slightly, but not significantly, reduced. In contrast, neonatally administered TP had no effect on either the concentration of cytoplasmic estradiol-binding sites or uterine responsiveness. Nuclear binding of estradiol was unaffected by either TP or EB treatment in both age groups. In a futher experiment in rats ovariectomized at 9 days of age, those treated neonatally with EB had significantly smaller uteri than their untreated ovariectomized controls, thus providing indirect evidence for an extravarian factor affected by neonatal treatment. These data support the hypothesis that neonatal EB treatment may directly inhibit the synthesis or replenishment of the 8S estradiol \"receptor\" prior to the development of the persistent estrus syndrome (persistent vaginal estrus, anovulation and polycystic ovaries). A neonatally-induced neuroendocrine disorder affecting steroid secretion by the ovary or adrenal may also exist prepubertally to account for the uterine defects."}
{"id": "PMID:12936", "title": "Lack of glucose effect on the induction of 5-aminolevulinate synthetase and tyrosine aminotransferase in the isolated perfused rat liver.", "content": "In the isolated perfused rat liver, both 5-aminolevulinate synthetase and tyrosine aminotransferase were induced by the addition of 3.5 mmol/l allylisopropylacetamide and 58 mumol/l dexamethasone to the perfusion medium. Glucose (40 mmol/l) did not affect either the induction of these enzymes or the intrahepatic level of cyclic AMP. The results suggest that the glucose effect on the induction of 5-aminolevulinate synthetase and tyrosine aminotransferase in vivo is mediated by extrahepatic factors.", "contents": "Lack of glucose effect on the induction of 5-aminolevulinate synthetase and tyrosine aminotransferase in the isolated perfused rat liver. In the isolated perfused rat liver, both 5-aminolevulinate synthetase and tyrosine aminotransferase were induced by the addition of 3.5 mmol/l allylisopropylacetamide and 58 mumol/l dexamethasone to the perfusion medium. Glucose (40 mmol/l) did not affect either the induction of these enzymes or the intrahepatic level of cyclic AMP. The results suggest that the glucose effect on the induction of 5-aminolevulinate synthetase and tyrosine aminotransferase in vivo is mediated by extrahepatic factors."}
{"id": "PMID:12938", "title": "Inhibition of L-asparagine synthetase by mucochloric and mucobromic acids.", "content": "Mucochloric and mucobromic acids are powerful inhibitors of tumoral and pancreatic L-asparagine synthetases. Two nitrogen donors, L-glutamine and ammonia, can be used by these enzymes; at a concentration of 1 mmol/l, mucochloric and mucobromic acids preferentially inhibit the utilization of ammonia as opposed to L-glutamine in vitro. Using the tumoral enzyme, kinetic analysis revealed that mucochloric acid produced inhibition which was apparently noncompetitive with ammonia but competitive with L-glutamine. In molar excess, L-glutamine and dithiothreitol effectively antagonized such inhibition; dialysis, however, failed to reverse established inhibition. These findings, suggest that the drugs operate by covalent attachment to crucial sulfhydryl functions on the enzyme.", "contents": "Inhibition of L-asparagine synthetase by mucochloric and mucobromic acids. Mucochloric and mucobromic acids are powerful inhibitors of tumoral and pancreatic L-asparagine synthetases. Two nitrogen donors, L-glutamine and ammonia, can be used by these enzymes; at a concentration of 1 mmol/l, mucochloric and mucobromic acids preferentially inhibit the utilization of ammonia as opposed to L-glutamine in vitro. Using the tumoral enzyme, kinetic analysis revealed that mucochloric acid produced inhibition which was apparently noncompetitive with ammonia but competitive with L-glutamine. In molar excess, L-glutamine and dithiothreitol effectively antagonized such inhibition; dialysis, however, failed to reverse established inhibition. These findings, suggest that the drugs operate by covalent attachment to crucial sulfhydryl functions on the enzyme."}
{"id": "PMID:12937", "title": "Mitochondrial isocitrate dehydrogenase and isocitrate oxidation of rat ventral prostate.", "content": "Mitochondrial preparations isolated from rat ventral prostate were capable of oxidizing isocitrate by way of NADP isocitrate dehydrogenase (NADP-IDH) and NAD-IDH. NAD-IDH activity required ADP for activation. The pH responses for NAD-IDH and NADP-IDH were quite different. The results indicated that two different enzymes were involved in the NAD- and NADP-IDH activities. Indirect evidence indicated that NADPH-NAD transhydrogenase activity might also be involved in the mitochondrial pathway for isocitrate oxidation. NADP-IDH activity was significantly greater than NAD-IDH activity. The oxidation of isocitrate through IDH activity was coupled to the cytochrome system by NADPH- and NADH-cytochrome c reductase activities. Citrate, via isocitrate, oxidation proceeded at a much slower rate suggesting that aconitase activity could be limiting in the oxidation of citrate. In comparison to other tissues, the prostate oxidative enzyme activities are considerably lower. The results suggest that the accumulation of high prostate citrate levels is not due to a limitation imposed by a lack of IDH activity in prostate mitochondria.", "contents": "Mitochondrial isocitrate dehydrogenase and isocitrate oxidation of rat ventral prostate. Mitochondrial preparations isolated from rat ventral prostate were capable of oxidizing isocitrate by way of NADP isocitrate dehydrogenase (NADP-IDH) and NAD-IDH. NAD-IDH activity required ADP for activation. The pH responses for NAD-IDH and NADP-IDH were quite different. The results indicated that two different enzymes were involved in the NAD- and NADP-IDH activities. Indirect evidence indicated that NADPH-NAD transhydrogenase activity might also be involved in the mitochondrial pathway for isocitrate oxidation. NADP-IDH activity was significantly greater than NAD-IDH activity. The oxidation of isocitrate through IDH activity was coupled to the cytochrome system by NADPH- and NADH-cytochrome c reductase activities. Citrate, via isocitrate, oxidation proceeded at a much slower rate suggesting that aconitase activity could be limiting in the oxidation of citrate. In comparison to other tissues, the prostate oxidative enzyme activities are considerably lower. The results suggest that the accumulation of high prostate citrate levels is not due to a limitation imposed by a lack of IDH activity in prostate mitochondria."}
{"id": "PMID:12939", "title": "Congenital methylmalonic acidemia: a variant of the B12 'non-responsive' form with evidence for reduced affinity of methylmalonyl-CoA mutase for its B12-coenzyme.", "content": "Methylmalonate metabolism was investigated in fibroblasts and leukocytes of two unrelated patient with a B12-nonresponsive type of congenital methylmalonic acidemia. Intact fibroblasts from both patients showed a defective metabolism of methyl-14 c-malonate to 14CO2, whereas no such defect was found in their intact peripheral leukocytes. In disrupted fibroblasts, the conversion of methylmalonyl coenzyme A to succinyl coenzyme A was markedly reduced but was completely normalized by the addition of 5'-deoxyadenosylcobalamin (AdoCb1; 10(-5) mol/l), the specific coenzyme of methylmalonyl coenzyme A mutase. Assays with decreasing concentrations of AdoCbl (10(-5)-10(-11) mol/l) suggested a reduced affinity of the mutase apoenzyme for its coenzyme, implicating yet another variant of this heterogeneous disease.", "contents": "Congenital methylmalonic acidemia: a variant of the B12 'non-responsive' form with evidence for reduced affinity of methylmalonyl-CoA mutase for its B12-coenzyme. Methylmalonate metabolism was investigated in fibroblasts and leukocytes of two unrelated patient with a B12-nonresponsive type of congenital methylmalonic acidemia. Intact fibroblasts from both patients showed a defective metabolism of methyl-14 c-malonate to 14CO2, whereas no such defect was found in their intact peripheral leukocytes. In disrupted fibroblasts, the conversion of methylmalonyl coenzyme A to succinyl coenzyme A was markedly reduced but was completely normalized by the addition of 5'-deoxyadenosylcobalamin (AdoCb1; 10(-5) mol/l), the specific coenzyme of methylmalonyl coenzyme A mutase. Assays with decreasing concentrations of AdoCbl (10(-5)-10(-11) mol/l) suggested a reduced affinity of the mutase apoenzyme for its coenzyme, implicating yet another variant of this heterogeneous disease."}
{"id": "PMID:12941", "title": "Biosynthesis of peptidoglycan in Gaffkya homari. The mode of action of penicillin G and mecillinam.", "content": "The effect of the beta-lactam antibiotics penicillin G and mecillinam on the incorporation of peptidoglycan into pre-formed cell wall peptidoglycan was studied with wall membrane enzyme preparations from Gaffkya homari. Using UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-pentapeptide) as precursors the incorporation of peptidoglycan into the pre-existing cell wall of G. homari was inhibited to an extent of 50% (ID50 value) at a concentration of 0.25 mug of penicillin G/ml. With UDP-GlcNAc and UDP-MurNAc-tetrapeptide as precursors the ID50 value was about 2500-fold greater (630 mug/ml). The inhibition by penicillin G of the incorporation of peptidoglycan from UDP-MurNAc-[14C]Lys-pentapeptide could be overcome by addition of non-radioactive UDP-MurNAc-tetrapeptide to the incubation mixture. In the presence of 5 mug of penicillin G/ml the incorporation of peptidoglycan formed from the mixture of UDP-MurNAc-Ala-DGlu-Lys-D-[14C]Ala-D[14C]Ala and non-radioactive UDP-MurNAc-tetrapeptide proceeded virtually without release of D-[14C]alanine by transpeptidase activity. The enzyme preparation also exhibited DD-carboxypeptidase activity which was only slightly more sensitive to penicillin G and mecillinam than was the incorporation of peptidoglycan into the cell wall. Since the ID50 values for the beta-lactam antibiotics are similar to the concentrations required to inhibit the growth of G. homari to an extent of 50%, the DD-carboxypeptidase must be the killing site of both penicillin G and mecillinam.", "contents": "Biosynthesis of peptidoglycan in Gaffkya homari. The mode of action of penicillin G and mecillinam. The effect of the beta-lactam antibiotics penicillin G and mecillinam on the incorporation of peptidoglycan into pre-formed cell wall peptidoglycan was studied with wall membrane enzyme preparations from Gaffkya homari. Using UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-pentapeptide) as precursors the incorporation of peptidoglycan into the pre-existing cell wall of G. homari was inhibited to an extent of 50% (ID50 value) at a concentration of 0.25 mug of penicillin G/ml. With UDP-GlcNAc and UDP-MurNAc-tetrapeptide as precursors the ID50 value was about 2500-fold greater (630 mug/ml). The inhibition by penicillin G of the incorporation of peptidoglycan from UDP-MurNAc-[14C]Lys-pentapeptide could be overcome by addition of non-radioactive UDP-MurNAc-tetrapeptide to the incubation mixture. In the presence of 5 mug of penicillin G/ml the incorporation of peptidoglycan formed from the mixture of UDP-MurNAc-Ala-DGlu-Lys-D-[14C]Ala-D[14C]Ala and non-radioactive UDP-MurNAc-tetrapeptide proceeded virtually without release of D-[14C]alanine by transpeptidase activity. The enzyme preparation also exhibited DD-carboxypeptidase activity which was only slightly more sensitive to penicillin G and mecillinam than was the incorporation of peptidoglycan into the cell wall. Since the ID50 values for the beta-lactam antibiotics are similar to the concentrations required to inhibit the growth of G. homari to an extent of 50%, the DD-carboxypeptidase must be the killing site of both penicillin G and mecillinam."}
{"id": "PMID:12942", "title": "pK changes of ionizable reporter groups as an index of conformational changes in proteins. A study of fluorescein-labelled ribonuclease A.", "content": "A chemical derivative of bovine pancreatic ribonuclease A (RNase A) has been prepared by reaction with fluorescein-isothiocyanate at pH 6. This derivative has a fluorescein group covalently attached to the alpha-amino group of the protein. The enzymic properties of the modified protein are similar to those of RNase A. It is shown that the pK of the fluorescein group can be used as an index of protein conformation to monitor structural changes in the protein. In this work, the binding of a specific inhibitor (cytidine 2'-monophosphate) to RNase A, the isomerization process occurring in RNase A around pH 6, and the thermal unfolding of RNase A, were studied by mean of the pK changes of the fluorescein group. The results obtained by this method are fully consistent with those obtained by other methods. It is proposed that using ionizable reporter groups and their changes in pK to monitor conformational changes in proteins may be a sensitive tool both in equilibrium and kinetic studies.", "contents": "pK changes of ionizable reporter groups as an index of conformational changes in proteins. A study of fluorescein-labelled ribonuclease A. A chemical derivative of bovine pancreatic ribonuclease A (RNase A) has been prepared by reaction with fluorescein-isothiocyanate at pH 6. This derivative has a fluorescein group covalently attached to the alpha-amino group of the protein. The enzymic properties of the modified protein are similar to those of RNase A. It is shown that the pK of the fluorescein group can be used as an index of protein conformation to monitor structural changes in the protein. In this work, the binding of a specific inhibitor (cytidine 2'-monophosphate) to RNase A, the isomerization process occurring in RNase A around pH 6, and the thermal unfolding of RNase A, were studied by mean of the pK changes of the fluorescein group. The results obtained by this method are fully consistent with those obtained by other methods. It is proposed that using ionizable reporter groups and their changes in pK to monitor conformational changes in proteins may be a sensitive tool both in equilibrium and kinetic studies."}
{"id": "PMID:12943", "title": "The determination of the membrane ptoential of Chlorella vulgaris. Evidence for electrogenic sugar transport.", "content": "From data on the accumulation of tetraphenylphosphonium within Chlorella vulgaris cells, it can be estimated that these cells possess a membrane potential of --120 to --150 mV (inside negative). Under anaerobic conditions as well as in the presence of uncoupling agents the membrane potential drops to about -60 to -80 mV. Nystatin (50 mug/ml) abolishes it almost completely. Since it took more than 1 h before the tetraphenylphosphonium equilibrium was reached, this method could not be used to measure relatively fast transient changes in membrane potential. However, the rate of influx of tetraphenylphosphonium is also directly dependent on membrane potential and can be followed within minutes. Using this phenomenon as an indicator for membrane potential a brief transient depolarisation was detected after the addition of sugars taken up by Chlorella via the proton cotransport system. The depolarisation was absent from cells not induced for sugar uptake and induced cells did not show it with substances not transported, like mannitol. The maximal depolarisation observed amounted to about 70 mV; after 1 min, however, the membrane potential returned to a value about 25 mV less negative than the one before sugars was added. The results demonstrate that sugar uptake in Chlorella is electrogenic. The delta pH plus membrane potential measured for Chlorella completely cover the energy required to explain the 1600-fold accumulation of 6-deoxyglucose experimentally observed.", "contents": "The determination of the membrane ptoential of Chlorella vulgaris. Evidence for electrogenic sugar transport. From data on the accumulation of tetraphenylphosphonium within Chlorella vulgaris cells, it can be estimated that these cells possess a membrane potential of --120 to --150 mV (inside negative). Under anaerobic conditions as well as in the presence of uncoupling agents the membrane potential drops to about -60 to -80 mV. Nystatin (50 mug/ml) abolishes it almost completely. Since it took more than 1 h before the tetraphenylphosphonium equilibrium was reached, this method could not be used to measure relatively fast transient changes in membrane potential. However, the rate of influx of tetraphenylphosphonium is also directly dependent on membrane potential and can be followed within minutes. Using this phenomenon as an indicator for membrane potential a brief transient depolarisation was detected after the addition of sugars taken up by Chlorella via the proton cotransport system. The depolarisation was absent from cells not induced for sugar uptake and induced cells did not show it with substances not transported, like mannitol. The maximal depolarisation observed amounted to about 70 mV; after 1 min, however, the membrane potential returned to a value about 25 mV less negative than the one before sugars was added. The results demonstrate that sugar uptake in Chlorella is electrogenic. The delta pH plus membrane potential measured for Chlorella completely cover the energy required to explain the 1600-fold accumulation of 6-deoxyglucose experimentally observed."}
{"id": "PMID:12944", "title": "Translation of mRNA from rat-liver polysomes into tyrosine aminotransferase and tryptophan oxygenase in a protein-synthesizing system from wheat germ. Effects of cortisol on the translatable levels of mRNA for these two enzymes.", "content": "Messenger RNA was isolated from rat liver polysomes by phenol/chloroform extraction and subsequent oligo(dT)-cellulose chromatography. The mRNA was translated in a protein-synthesizing system in vitro derived from wheat germ. The system was optimized in respect to Mg2+ and K+. The presence of spermidine or spermine is necessary for the synthesis of polypeptides having molecular weights of over 20 000. In the absence of the bases only small molecular weight products are formed. The amount of protein synthesized is linearly dependent on the amount of mRNA added up to concentrations of 80 mug mRNA/ml. The synthesis of tyrosine aminotransferase and tryptophan oxygenase in the system in vitro has been demonstrated by specific immunoprecipitation and sodium-dodecylsulfate polyacrylamide gel electrophoresis of the precipitate with enzyme proteins as marker. The amount of specific product formed is linearly dependent on the amount of mRNA present. The amount of translatable tyrosine aminotransferase mRNA and tryptophan oxygenase mRNA increases after administration of hydrocortisone to adrenalectomized rats. At low doses of hormone (2 mg/100 g body weight) maximal values are observed at 4 h, control levels being reached at 6-8 h after hormone application. With higher doses of hydrocortisone (20 mg/100 g body weight) maximal values are attained at 6 h, tending to control levels 14 h after treatment. The enzyme activity curves are parallel to the mRNA curves, the peak of enzyme activity occurring 2 h after the peak of mRNA activity.", "contents": "Translation of mRNA from rat-liver polysomes into tyrosine aminotransferase and tryptophan oxygenase in a protein-synthesizing system from wheat germ. Effects of cortisol on the translatable levels of mRNA for these two enzymes. Messenger RNA was isolated from rat liver polysomes by phenol/chloroform extraction and subsequent oligo(dT)-cellulose chromatography. The mRNA was translated in a protein-synthesizing system in vitro derived from wheat germ. The system was optimized in respect to Mg2+ and K+. The presence of spermidine or spermine is necessary for the synthesis of polypeptides having molecular weights of over 20 000. In the absence of the bases only small molecular weight products are formed. The amount of protein synthesized is linearly dependent on the amount of mRNA added up to concentrations of 80 mug mRNA/ml. The synthesis of tyrosine aminotransferase and tryptophan oxygenase in the system in vitro has been demonstrated by specific immunoprecipitation and sodium-dodecylsulfate polyacrylamide gel electrophoresis of the precipitate with enzyme proteins as marker. The amount of specific product formed is linearly dependent on the amount of mRNA present. The amount of translatable tyrosine aminotransferase mRNA and tryptophan oxygenase mRNA increases after administration of hydrocortisone to adrenalectomized rats. At low doses of hormone (2 mg/100 g body weight) maximal values are observed at 4 h, control levels being reached at 6-8 h after hormone application. With higher doses of hydrocortisone (20 mg/100 g body weight) maximal values are attained at 6 h, tending to control levels 14 h after treatment. The enzyme activity curves are parallel to the mRNA curves, the peak of enzyme activity occurring 2 h after the peak of mRNA activity."}
{"id": "PMID:12945", "title": "1, 4-alpha-Glucan phosphorylase from Klebsiella pneumoniae purification, subunit structure and amino acid composition.", "content": "1. A 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae has been purified about 80-fold with an over-all yield greater than 35%. The purified enzyme has been shown to be homogeneous by gel electrophoresis at different pH-values, by isoelectric focusing, by dodecylsulfate electrophoresis and by ultracentrifugation. 2. The molecular weight of the native enzyme has been determined to be 180 000 by ultra-centrifugation studies, in good agreement with the value of 189 000 estimated by gel permeation chromatography. 3. The enzyme dissociates in the presence of 0.1% dodecylsulfate or 5 M guanidine hydrochloride into polypeptide chains. The molecular weight of these polypeptide chains has been found to be 88 000 by dodecylsulfate polyacrylamide gel electrophoresis and 99 000 by sedimentation equilibrium studies, indicating that the native enzyme is composed of two polypeptide chains. 4. The enzyme contains pyridoxalphosphate with a stoichiometry of two moles per 180 000 g protein, confirming that the 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae is a dimeric enzyme. 5. The amino acid composition of the enzyme has been determined, and its correspondence to that of 1,4-alpha-glucan phosphorylases from other sources is discussed. 6. The pI of the enzyme has been shown to be 5.3 and its pH-optimum to be about pH 5.9. The enzyme is stable in the range from pH 5.9 to 10.5.", "contents": "1, 4-alpha-Glucan phosphorylase from Klebsiella pneumoniae purification, subunit structure and amino acid composition. 1. A 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae has been purified about 80-fold with an over-all yield greater than 35%. The purified enzyme has been shown to be homogeneous by gel electrophoresis at different pH-values, by isoelectric focusing, by dodecylsulfate electrophoresis and by ultracentrifugation. 2. The molecular weight of the native enzyme has been determined to be 180 000 by ultra-centrifugation studies, in good agreement with the value of 189 000 estimated by gel permeation chromatography. 3. The enzyme dissociates in the presence of 0.1% dodecylsulfate or 5 M guanidine hydrochloride into polypeptide chains. The molecular weight of these polypeptide chains has been found to be 88 000 by dodecylsulfate polyacrylamide gel electrophoresis and 99 000 by sedimentation equilibrium studies, indicating that the native enzyme is composed of two polypeptide chains. 4. The enzyme contains pyridoxalphosphate with a stoichiometry of two moles per 180 000 g protein, confirming that the 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae is a dimeric enzyme. 5. The amino acid composition of the enzyme has been determined, and its correspondence to that of 1,4-alpha-glucan phosphorylases from other sources is discussed. 6. The pI of the enzyme has been shown to be 5.3 and its pH-optimum to be about pH 5.9. The enzyme is stable in the range from pH 5.9 to 10.5."}
{"id": "PMID:12946", "title": "Biosynthesis of peptidoglycan in Gaffkya homari. The incorporation of peptidoglycan into the cell wall and the direction of transpeptidation.", "content": "Wall membrane enzyme preparations from Gaffkya homari catalyze the formation of peptidoglycan from the precursor pairs: UDP-N-acetylglucosamine + UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla) and also from UDP-N-acetylglucosamine + UDP-N-acetylmuramyl-tetrapeptide (UDP-MurNAc-Ala-DGlu-Lys-DAla). Part of the reaction products is soluble in 2% sodium dodecylsfulfate whereas the other part is bound to pre-existing cell wall peptidoglycan. The incorporation into cell wall takes place by a transpeptidation reaction in which the D-alanyl-D-alanine sequences in the pre-existing cell wall function as donors and the epsilon-amino groups of the lysine residues in the newly synthesized peptidoglycan strands function as acceptors. Nepsilon-D-Alanyl-lysine linkages are formed. At saturating concentration of UDP-N-acetylglucosamine, the enzyme system exhibits similar apparent Km values (30--80 muM) for UDP-MurNAc-pentapeptide and UDP-MurNAc-tetrapeptide both for the formation of cell-wall bound peptidoglycan and total (i.e. soluble + cell-wall-bound) peptidoglycan. The V values are also in the same order of magnitude (270-650 pmol x min-1 x mg of protein -1). However, UDP-MurNAc-tetrapeptide was a slightly better substrate than UDP-MurNAc-pentapeptide for the formation of cell-wall-bound peptidoglucan. The synthesis of total and cell-wall-bound peptidoglycan from UDP-MurNAc-pentapeptide was competitively inhibited by UDP-MurNAc-tetrapeptide and vice versa. UDP-MurNAc-tripeptide and both UDP-Mur-NAc-pentapeptide and UDP-Mur-NAc-tetrapeptide in which the epsilon-amino group of the lysine residue was substituted by an acetyl group were utilized less efficiently than UDP-MurNAc-pentapeptide and UDP-MurNAc-tetrapeptide for the formation of soluble peptidoglycan; they were exceedingly poor substrates for the formation of cell-wall-bound peptidoglycan.", "contents": "Biosynthesis of peptidoglycan in Gaffkya homari. The incorporation of peptidoglycan into the cell wall and the direction of transpeptidation. Wall membrane enzyme preparations from Gaffkya homari catalyze the formation of peptidoglycan from the precursor pairs: UDP-N-acetylglucosamine + UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-Ala-DGlu-Lys-DAla-DAla) and also from UDP-N-acetylglucosamine + UDP-N-acetylmuramyl-tetrapeptide (UDP-MurNAc-Ala-DGlu-Lys-DAla). Part of the reaction products is soluble in 2% sodium dodecylsfulfate whereas the other part is bound to pre-existing cell wall peptidoglycan. The incorporation into cell wall takes place by a transpeptidation reaction in which the D-alanyl-D-alanine sequences in the pre-existing cell wall function as donors and the epsilon-amino groups of the lysine residues in the newly synthesized peptidoglycan strands function as acceptors. Nepsilon-D-Alanyl-lysine linkages are formed. At saturating concentration of UDP-N-acetylglucosamine, the enzyme system exhibits similar apparent Km values (30--80 muM) for UDP-MurNAc-pentapeptide and UDP-MurNAc-tetrapeptide both for the formation of cell-wall bound peptidoglycan and total (i.e. soluble + cell-wall-bound) peptidoglycan. The V values are also in the same order of magnitude (270-650 pmol x min-1 x mg of protein -1). However, UDP-MurNAc-tetrapeptide was a slightly better substrate than UDP-MurNAc-pentapeptide for the formation of cell-wall-bound peptidoglucan. The synthesis of total and cell-wall-bound peptidoglycan from UDP-MurNAc-pentapeptide was competitively inhibited by UDP-MurNAc-tetrapeptide and vice versa. UDP-MurNAc-tripeptide and both UDP-Mur-NAc-pentapeptide and UDP-Mur-NAc-tetrapeptide in which the epsilon-amino group of the lysine residue was substituted by an acetyl group were utilized less efficiently than UDP-MurNAc-pentapeptide and UDP-MurNAc-tetrapeptide for the formation of soluble peptidoglycan; they were exceedingly poor substrates for the formation of cell-wall-bound peptidoglycan."}
{"id": "PMID:12947", "title": "CO2 reduction to formate by NADH catalysed by formate dehydrogenase from Pseudomonas oxalaticus.", "content": "The direct reduction of CO2 to formate is catalysed by formate: NAD oxidoreductase in the presence of substrate amounts of NADH. Proof for this reaction is supplied by the detection of a CO2-dependent NADH oxidation, and by the identification of [14c] formate as the product of a NADH-dependent reduction of [14c]carbonate. The enzyme-catalysed CO2 reduction by NADH attains the equilibrium predicted by thermodynamic considerations, a state which is also reached from the formate side. The Michaelis constant for CO2 is about 40 mM indicating the low affinity of the enzyme for this substrate. The corresponding value for formate is 0.1 mM. Under the special conditions employed the enzyme catalyses the formate oxidation about 30 times faster than the CO2 reduction. That CO2 and not HCO3- is the active species in the reduction was shown by comparing the ph dependency of the velocities of the forward and back reactions and by observing the kinetics of CO2 reduction during the simultaneous attainment of the CO2-HCO3- equilibrium.", "contents": "CO2 reduction to formate by NADH catalysed by formate dehydrogenase from Pseudomonas oxalaticus. The direct reduction of CO2 to formate is catalysed by formate: NAD oxidoreductase in the presence of substrate amounts of NADH. Proof for this reaction is supplied by the detection of a CO2-dependent NADH oxidation, and by the identification of [14c] formate as the product of a NADH-dependent reduction of [14c]carbonate. The enzyme-catalysed CO2 reduction by NADH attains the equilibrium predicted by thermodynamic considerations, a state which is also reached from the formate side. The Michaelis constant for CO2 is about 40 mM indicating the low affinity of the enzyme for this substrate. The corresponding value for formate is 0.1 mM. Under the special conditions employed the enzyme catalyses the formate oxidation about 30 times faster than the CO2 reduction. That CO2 and not HCO3- is the active species in the reduction was shown by comparing the ph dependency of the velocities of the forward and back reactions and by observing the kinetics of CO2 reduction during the simultaneous attainment of the CO2-HCO3- equilibrium."}
{"id": "PMID:12948", "title": "Purification and properties of adductor muscle phosphofructokinase from the oyster, Crassostrea virginica. The aerobic/anaerobic transition: role of arginine phosphate in enzyme control.", "content": "Phosphofructokinase from oyster (Crassostrea virginica) adductor muscle occurs in a single electrophorectic form at an activity of 8.1 mumol of product formed per minute per gram wet weight. The enzyme was purified to homogeneity by a novel method involving extraction in dilute ethanol and subsequent precipitation with polyethylene glycol. Oyster adductor phosphofructokinase has a molecular weight of 3400000 +/- 20000 as measured by Sephadex gel chromatography. Mg2+ or Mn2+ can satisfy the divalent ion requirement while ATP, GTP, or ITP can serve as phosphate donors for the reaction. Oyster adductor phosphofructokinase displays hyperbolic saturation kinetics with respect to all substrates (fructose 6-phosphate, ATP, and Mg2+) at either pH 7.9 OR PH 6.8. The Michaelis constant for fructose 6 phosphate at pH 6.8, the cellular pH of anoxic oyster tissues, is 3.5 mM. In the presence of AMP, by far the most potent activator and deinhibitor of the enzyme, this drops to 0.70 mM. Many traditional effectors of phosphofructokinase including citrate, NAD(P)H,Ca2+, fructose 1,6-bisphosphate, 3-phosphoglycerate, ADP, and phosphoenolpyruvate do not alter enzyme activity when tested at their physiological concentrations. Monovalent ions (K +, NH4+) are activators of the enzyme. ATP and arginine phosphate are the only compounds found to inhibit the adductor enzyme. The inhibitory action of both can be reversed by physiological concentrations of AMP(0.2- 1.0mM) and to a lesser extent by high concentrations of Pi (20 mM) and adenosine 3' :5'-monophosphate (0.1 mM). The two inhibitors exhibit very different pH versus inhibition profiles. The Ki (ATP) decreases from 5.0 mM to 1.3 mM as the pH decreases from 7.9 to 6.8, whereas the Ki for arginine phosphate increases from 1.3 mM to 4.5 mM for the same pH drop. Of all compounds tested, only AMP, within its physiological range, activated adductor phosphofructokinase significantly at low pH values. The kinetic data support the proposal that arginine phosphate, not ATP or citrate, is the most likely regulator of adductor phosphofructokinase in vivo under aerobic, high tissue pH, conditions. In anoxia, the depletion of arginine phosphate reserves and the increase in AMP concentrations in the tissue, coupled with the increase in the Ki for arginine phosphate brought about by low pH conditions, serves to activate phosphofructokinase to aid maintenance of anaerobic energy production.", "contents": "Purification and properties of adductor muscle phosphofructokinase from the oyster, Crassostrea virginica. The aerobic/anaerobic transition: role of arginine phosphate in enzyme control. Phosphofructokinase from oyster (Crassostrea virginica) adductor muscle occurs in a single electrophorectic form at an activity of 8.1 mumol of product formed per minute per gram wet weight. The enzyme was purified to homogeneity by a novel method involving extraction in dilute ethanol and subsequent precipitation with polyethylene glycol. Oyster adductor phosphofructokinase has a molecular weight of 3400000 +/- 20000 as measured by Sephadex gel chromatography. Mg2+ or Mn2+ can satisfy the divalent ion requirement while ATP, GTP, or ITP can serve as phosphate donors for the reaction. Oyster adductor phosphofructokinase displays hyperbolic saturation kinetics with respect to all substrates (fructose 6-phosphate, ATP, and Mg2+) at either pH 7.9 OR PH 6.8. The Michaelis constant for fructose 6 phosphate at pH 6.8, the cellular pH of anoxic oyster tissues, is 3.5 mM. In the presence of AMP, by far the most potent activator and deinhibitor of the enzyme, this drops to 0.70 mM. Many traditional effectors of phosphofructokinase including citrate, NAD(P)H,Ca2+, fructose 1,6-bisphosphate, 3-phosphoglycerate, ADP, and phosphoenolpyruvate do not alter enzyme activity when tested at their physiological concentrations. Monovalent ions (K +, NH4+) are activators of the enzyme. ATP and arginine phosphate are the only compounds found to inhibit the adductor enzyme. The inhibitory action of both can be reversed by physiological concentrations of AMP(0.2- 1.0mM) and to a lesser extent by high concentrations of Pi (20 mM) and adenosine 3' :5'-monophosphate (0.1 mM). The two inhibitors exhibit very different pH versus inhibition profiles. The Ki (ATP) decreases from 5.0 mM to 1.3 mM as the pH decreases from 7.9 to 6.8, whereas the Ki for arginine phosphate increases from 1.3 mM to 4.5 mM for the same pH drop. Of all compounds tested, only AMP, within its physiological range, activated adductor phosphofructokinase significantly at low pH values. The kinetic data support the proposal that arginine phosphate, not ATP or citrate, is the most likely regulator of adductor phosphofructokinase in vivo under aerobic, high tissue pH, conditions. In anoxia, the depletion of arginine phosphate reserves and the increase in AMP concentrations in the tissue, coupled with the increase in the Ki for arginine phosphate brought about by low pH conditions, serves to activate phosphofructokinase to aid maintenance of anaerobic energy production."}
{"id": "PMID:12949", "title": "Efficient purification and molecular properties of spinach chloroplast fructose 1,6-bisphosphatase.", "content": "A relatively straightforward procedure has been developed for the purification of chloroplast fructose bisphosphatase from spinach leaves to apparent homogeneity and with 80% yield. The molecular weight of the enzyme was about 160 000. Chloroplast fructosebisphosphatase consists of four possibly identical subunits and, at pH 8.8, EASILY DISSOCIATES INTO EQUAL HALVES WITH LOWered activity. Sigmoid saturation curves with Hill coefficients between 3.0 and 3.7 were obtained for fructose 1,6-bisphosphate and Mg2+. Incubation of the enzyme with 20 mM dithiothreitol slowly altered the response to pH from no activity measured at pH 7.5 and full activity at pH 8.8 to equal activity at each of these pH values; at the same time the number of freely available sulphydryl groups increased from four to twelve per molecule. These properties are considered in the context of the observed activation of this enzyme following illumination of chloroplasts.", "contents": "Efficient purification and molecular properties of spinach chloroplast fructose 1,6-bisphosphatase. A relatively straightforward procedure has been developed for the purification of chloroplast fructose bisphosphatase from spinach leaves to apparent homogeneity and with 80% yield. The molecular weight of the enzyme was about 160 000. Chloroplast fructosebisphosphatase consists of four possibly identical subunits and, at pH 8.8, EASILY DISSOCIATES INTO EQUAL HALVES WITH LOWered activity. Sigmoid saturation curves with Hill coefficients between 3.0 and 3.7 were obtained for fructose 1,6-bisphosphate and Mg2+. Incubation of the enzyme with 20 mM dithiothreitol slowly altered the response to pH from no activity measured at pH 7.5 and full activity at pH 8.8 to equal activity at each of these pH values; at the same time the number of freely available sulphydryl groups increased from four to twelve per molecule. These properties are considered in the context of the observed activation of this enzyme following illumination of chloroplasts."}
{"id": "PMID:12950", "title": "Enzyme reduction of disulfide bonds by thioredoxin. The reactivity of disulfide bonds in human choriogonadotropin and its subunits.", "content": "The NADPH-dependent enzymic reduction of disulfide bonds in human choriogonadotropin and its two subunits, alpha and beta, was examined with thioredoxin and thioredoxin reductase from Escherichia coli. With 12 muM thioredoxin and 0.1 muM thioredoxin reductase at pH 7 all disulfide bonds in the alpha subunit could be reduced in 15 min. The reduction of disulfide bonds was recorded by a simple spectrophotometric assay at 340 nm, which allowed quantitation of the reduction rate and the number of disulfide bonds reduced. Partial reduction of the alpha subunit with thioredoxin followed by S-carboxymethylation with iodol[2-3H]acetic acid and analysis of tryptic peptides indicated that all S-S bonds in the alpha subunit were surface oriented and equally reactive. The usefulness of thioredoxin reduction of disulfide bonds as a chemical probe of protein structure was shown by the much slower reaction of disulfide bonds in the intact hormone as compared to its two biologically inactive subunits.", "contents": "Enzyme reduction of disulfide bonds by thioredoxin. The reactivity of disulfide bonds in human choriogonadotropin and its subunits. The NADPH-dependent enzymic reduction of disulfide bonds in human choriogonadotropin and its two subunits, alpha and beta, was examined with thioredoxin and thioredoxin reductase from Escherichia coli. With 12 muM thioredoxin and 0.1 muM thioredoxin reductase at pH 7 all disulfide bonds in the alpha subunit could be reduced in 15 min. The reduction of disulfide bonds was recorded by a simple spectrophotometric assay at 340 nm, which allowed quantitation of the reduction rate and the number of disulfide bonds reduced. Partial reduction of the alpha subunit with thioredoxin followed by S-carboxymethylation with iodol[2-3H]acetic acid and analysis of tryptic peptides indicated that all S-S bonds in the alpha subunit were surface oriented and equally reactive. The usefulness of thioredoxin reduction of disulfide bonds as a chemical probe of protein structure was shown by the much slower reaction of disulfide bonds in the intact hormone as compared to its two biologically inactive subunits."}
{"id": "PMID:12951", "title": "Studies on 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe) from Escherichia coli K12. 1. Purification and subunit structure.", "content": "1. 3-Deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe) from Escherichia coli K12 has been purified to near homogeneity. The purified enzyme has a specific activity of 67 units/mg which is about 1000 times that found in cell-free extracts of wild-tupe E. coli K12. 2. The minimum molecular weight of the enzyme was estimated by dodecylsuphate-gel electrophoresis to be 33000. Re-estimation of the native molecular weight by gel filtration confirmed the previously determined value of 110000. 3. Amino acid anaktsus abd tryptic fingerprints indicated that the subunits of the enzyme are very similar and possibly identical. 4. The purified enzyme does not contain Co2+.", "contents": "Studies on 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe) from Escherichia coli K12. 1. Purification and subunit structure. 1. 3-Deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe) from Escherichia coli K12 has been purified to near homogeneity. The purified enzyme has a specific activity of 67 units/mg which is about 1000 times that found in cell-free extracts of wild-tupe E. coli K12. 2. The minimum molecular weight of the enzyme was estimated by dodecylsuphate-gel electrophoresis to be 33000. Re-estimation of the native molecular weight by gel filtration confirmed the previously determined value of 110000. 3. Amino acid anaktsus abd tryptic fingerprints indicated that the subunits of the enzyme are very similar and possibly identical. 4. The purified enzyme does not contain Co2+."}
{"id": "PMID:12952", "title": "Studies on 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe)from Escherichia coli K12. 2. Kinetic properties.", "content": "1. Co2+ is not a cofactor for 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe). 2. The following analogues of phosphoenolpyruvate were tested as inhibitors of 3-deoxy-D-arabinoheptolosonate-7-phosphate synthetase(phe): pyruvate, lactate, glycerate, 2-phosphoglycerate, 2,3-bisphosphoglycerate, 3-methylphosphoenolpyruvate, 3-ethylphosphoenolpyruvate and 3,3-demethylphosphoenolpyruvate. The rusults obtained indicate that the binding of phosphoenolpyruvate to the enzyme requires a phosphoryl group on the C-2 position of the substrate and one free hydrogen atom at the C-3 position. 3. The dead-end inhibition pattern observed with the substrate analogue 2-phosphoglycerate when either phosphoenolpyruvate or erythrose 4-phosphate was the variable substrate is inconsistent with a ping-pong mechanism and indicates that the reaction mechanism for this enzyme must be sequential. The following kinetic constants were determined:Km for phosphoenolpyruvate, 0.08 +/- 0.04 mM; Km for erythrose 4-phosphate, 0.9 +/- 0.3 mM; K is for competitive inhibition by 2-phosphoglycerate with respect to phosphoenolpyruvate, 1.0 +/- 0.1 mM. 4. The enzyme was observed to have a bell-shaped pH PROFILE WITH A PH OPTIMUM OF 7.0. The effects of pH ON V and V/(Km for phosphoenolpyruvate) indicated that an ionizing group of pKa 8.0-8.1 is involved in the catalytic activity of the enzyme. The pKa of this group is unaffected by the binding of phosphoenolpyruvate.", "contents": "Studies on 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe)from Escherichia coli K12. 2. Kinetic properties. 1. Co2+ is not a cofactor for 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe). 2. The following analogues of phosphoenolpyruvate were tested as inhibitors of 3-deoxy-D-arabinoheptolosonate-7-phosphate synthetase(phe): pyruvate, lactate, glycerate, 2-phosphoglycerate, 2,3-bisphosphoglycerate, 3-methylphosphoenolpyruvate, 3-ethylphosphoenolpyruvate and 3,3-demethylphosphoenolpyruvate. The rusults obtained indicate that the binding of phosphoenolpyruvate to the enzyme requires a phosphoryl group on the C-2 position of the substrate and one free hydrogen atom at the C-3 position. 3. The dead-end inhibition pattern observed with the substrate analogue 2-phosphoglycerate when either phosphoenolpyruvate or erythrose 4-phosphate was the variable substrate is inconsistent with a ping-pong mechanism and indicates that the reaction mechanism for this enzyme must be sequential. The following kinetic constants were determined:Km for phosphoenolpyruvate, 0.08 +/- 0.04 mM; Km for erythrose 4-phosphate, 0.9 +/- 0.3 mM; K is for competitive inhibition by 2-phosphoglycerate with respect to phosphoenolpyruvate, 1.0 +/- 0.1 mM. 4. The enzyme was observed to have a bell-shaped pH PROFILE WITH A PH OPTIMUM OF 7.0. The effects of pH ON V and V/(Km for phosphoenolpyruvate) indicated that an ionizing group of pKa 8.0-8.1 is involved in the catalytic activity of the enzyme. The pKa of this group is unaffected by the binding of phosphoenolpyruvate."}
{"id": "PMID:12953", "title": "Studies on 3-deoxy-d-arabinoheptulosonate-7-phosphate synthetase(phe) from escherichia coli k12. 3. Structural studies.", "content": "1. Investigations with structural analogues of phenylalanine indicated an absolute requirement for the aromatic ring and both the alpha-carboxyl and alpha-amino groups of phenylalanine for inhibition of 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe) activity. Replacement of the alpha-H atom with a methyl group does not decrease the inhibition greatly. Varying degrees of inhibition were observed with o, m and p mono-substituted fluoro, chloro and hydroxy phenylalanines. D-Phenylalanine and several metabolites of the aromatic biosynthetic pathways do not inhibit enzymic activity. 2. Circular dichroism studies indicated that the native enzyme possesses approximately 26% alpha-helix. Both circular dichroic and ultraviolet difference spectra indicated that the addition of phenylalanine to the synthetase induces a conformational change involving a small alteration of the secondary structure and large alterations in th interactions of some of the aromatic residues of the enzyme. In particular, a tryptophan residue moves from an extremly hydrophobic environment to one less hydrophobic. 3. Kd for the binding of phenylalanine to the enzyme was determined spectrophotometrically to be 75 muM. 4. Chemical modification studies suggested that a sulphydryl group and possibly a lysine residue may be implicated in the catalytic activity of the enzyme.", "contents": "Studies on 3-deoxy-d-arabinoheptulosonate-7-phosphate synthetase(phe) from escherichia coli k12. 3. Structural studies. 1. Investigations with structural analogues of phenylalanine indicated an absolute requirement for the aromatic ring and both the alpha-carboxyl and alpha-amino groups of phenylalanine for inhibition of 3-deoxy-D-arabinoheptulosonate-7-phosphate synthetase(phe) activity. Replacement of the alpha-H atom with a methyl group does not decrease the inhibition greatly. Varying degrees of inhibition were observed with o, m and p mono-substituted fluoro, chloro and hydroxy phenylalanines. D-Phenylalanine and several metabolites of the aromatic biosynthetic pathways do not inhibit enzymic activity. 2. Circular dichroism studies indicated that the native enzyme possesses approximately 26% alpha-helix. Both circular dichroic and ultraviolet difference spectra indicated that the addition of phenylalanine to the synthetase induces a conformational change involving a small alteration of the secondary structure and large alterations in th interactions of some of the aromatic residues of the enzyme. In particular, a tryptophan residue moves from an extremly hydrophobic environment to one less hydrophobic. 3. Kd for the binding of phenylalanine to the enzyme was determined spectrophotometrically to be 75 muM. 4. Chemical modification studies suggested that a sulphydryl group and possibly a lysine residue may be implicated in the catalytic activity of the enzyme."}
{"id": "PMID:12954", "title": "A method for measuring the internal pH in illuminated chloroplasts based on the stimulation of proton uptake by amines.", "content": "A simple method for measuring the internal pH of chloroplasts during steady-state illuminations based on the stimulation of proton uptake by monofunctional amines was developed. Predictions of a mathematical derivation concerning the dependence of the stimulation on the amine concentration, the internal volume, the pK of the amine and the external pH have been verified experimentally. To circumvent uncoupling and swelling due to large internal accumulation of amines extrapolation of the stimulation to low amine concentrations was suggested and shown to lead to valid values. Alternatively, swelling could be largely reduced in a medium containing potassium aspartate and valinomycin.", "contents": "A method for measuring the internal pH in illuminated chloroplasts based on the stimulation of proton uptake by amines. A simple method for measuring the internal pH of chloroplasts during steady-state illuminations based on the stimulation of proton uptake by monofunctional amines was developed. Predictions of a mathematical derivation concerning the dependence of the stimulation on the amine concentration, the internal volume, the pK of the amine and the external pH have been verified experimentally. To circumvent uncoupling and swelling due to large internal accumulation of amines extrapolation of the stimulation to low amine concentrations was suggested and shown to lead to valid values. Alternatively, swelling could be largely reduced in a medium containing potassium aspartate and valinomycin."}
{"id": "PMID:12955", "title": "Effect of thyroid hormones on microsomal fatty acid chain elongation synthesis in rat liver.", "content": "Evidence is presented that rat liver microsomal fatty acid chain elongation synthesis and desaturation, as well as acetyl-CoA carboxylase and fatty acid synthetase, are strongly influenced by thyroid hormone level. Conversely, the fatty acid chain elongation system in mitochondria, unlike the oxidative capacity of palmitate, NADH, succinate and malate, does not seem significantly affected by the thyrotoxic state. In triiodothyronine-induced or thyroxine-induced hyperthyroidism, rat liver acetyl-CoA carboxylase, fatty acid synthetase and microsomal chain elongation and desaturation reactions are not greatly affected after the first 10 days of treatment, while after longer intervals a respective increase in these activities is shown of up to 87, 116 and 65% after 22 days. In propylthiouracil-induced hypothyroidism, all the above synthetic activities are strongly reduced immediately after three days of drug administration and diminished no further following longer periods. Although the pattern of synthesized fatty acids in the thyrotoxic state is similar to that obtained from normal subcellular rat fractions, the esterification process of fatty acids in microsomal lipids appears to be slightly inhibited in hypothyroid rats and increased following triiodothyronine or thyroxine administration. Finally, a reduction in the hepatic cyclic AMP level of about 41% is reported after 19 days of triiodothyronine-administration to rats. On the basis of the observed insensitivity of the mitochondrial fatty acid chain elongation system to the thyrotoxic state, a tentative interpretation of its role in the hepatic cell is postulated.", "contents": "Effect of thyroid hormones on microsomal fatty acid chain elongation synthesis in rat liver. Evidence is presented that rat liver microsomal fatty acid chain elongation synthesis and desaturation, as well as acetyl-CoA carboxylase and fatty acid synthetase, are strongly influenced by thyroid hormone level. Conversely, the fatty acid chain elongation system in mitochondria, unlike the oxidative capacity of palmitate, NADH, succinate and malate, does not seem significantly affected by the thyrotoxic state. In triiodothyronine-induced or thyroxine-induced hyperthyroidism, rat liver acetyl-CoA carboxylase, fatty acid synthetase and microsomal chain elongation and desaturation reactions are not greatly affected after the first 10 days of treatment, while after longer intervals a respective increase in these activities is shown of up to 87, 116 and 65% after 22 days. In propylthiouracil-induced hypothyroidism, all the above synthetic activities are strongly reduced immediately after three days of drug administration and diminished no further following longer periods. Although the pattern of synthesized fatty acids in the thyrotoxic state is similar to that obtained from normal subcellular rat fractions, the esterification process of fatty acids in microsomal lipids appears to be slightly inhibited in hypothyroid rats and increased following triiodothyronine or thyroxine administration. Finally, a reduction in the hepatic cyclic AMP level of about 41% is reported after 19 days of triiodothyronine-administration to rats. On the basis of the observed insensitivity of the mitochondrial fatty acid chain elongation system to the thyrotoxic state, a tentative interpretation of its role in the hepatic cell is postulated."}
{"id": "PMID:12956", "title": "Esterolytic activities of rat intestinal mucosa. 1. Characterization, cellular distribution and subcellular localization of a glycerol-ester hydrolase.", "content": "The preferential cellular distribution in the villus tip and the subcellular localization in the endoplasmic reticulum of an intestinal glycerol-ester hydrolase from rat mucosa are described. The enzyme is shown not to be from either pancreatic or bacterial origin; it catalyzes the hydrolysis of short- and medium chain triglycerides and of p-nitrophenylacetate. Contrarily to the specificity found for the pig intestinal lipase (Serrero, N\u00e9grel and Ailhaud, 1975), no activity is detectable against acylCoA; a thiolester hydrolase different from the glycerol-ester hydrolase was demonstrated after differential solubilization and chromatographic separation. A high proportion of glycerol-ester hydrolase is present in the intestinal lumen; its possible complementary role in lipid degradation is discussed.", "contents": "Esterolytic activities of rat intestinal mucosa. 1. Characterization, cellular distribution and subcellular localization of a glycerol-ester hydrolase. The preferential cellular distribution in the villus tip and the subcellular localization in the endoplasmic reticulum of an intestinal glycerol-ester hydrolase from rat mucosa are described. The enzyme is shown not to be from either pancreatic or bacterial origin; it catalyzes the hydrolysis of short- and medium chain triglycerides and of p-nitrophenylacetate. Contrarily to the specificity found for the pig intestinal lipase (Serrero, N\u00e9grel and Ailhaud, 1975), no activity is detectable against acylCoA; a thiolester hydrolase different from the glycerol-ester hydrolase was demonstrated after differential solubilization and chromatographic separation. A high proportion of glycerol-ester hydrolase is present in the intestinal lumen; its possible complementary role in lipid degradation is discussed."}
{"id": "PMID:12957", "title": "Esterolytic activities of rat intestinal mucosa. 2. Purification and properties of a glycerol-ester hydrolase.", "content": "A glycerol-ester hydrolase from rat intestinal cells has been purified using chromatography on carboxyhexanoyl-Sepharose-glyceryldioctanoate and preparative gel electrophoresis. The enzyme gives a single band by analytical gel electrophoresis; it is a monomer of molecular weight 68000. The optimum pH for its action on glyceryl tributyrate is between 8.0 and 8.5; the activation energy was calculated to be 8.7 kcal x mol-1 (36.4 kJ/mol). Its substrate specificity is mainly directed against esters of glycerol and of primary monoalcohols. Similarly to pancreatic lipase but contrary to liver esterase, it is inhibited by bile salts; relief of this inhibition by colipase is only observed for pancreatic lipase. The possible role of the glycerol-ester hydrolase in the absorption of short and of medium chain triglycerides is discussed.", "contents": "Esterolytic activities of rat intestinal mucosa. 2. Purification and properties of a glycerol-ester hydrolase. A glycerol-ester hydrolase from rat intestinal cells has been purified using chromatography on carboxyhexanoyl-Sepharose-glyceryldioctanoate and preparative gel electrophoresis. The enzyme gives a single band by analytical gel electrophoresis; it is a monomer of molecular weight 68000. The optimum pH for its action on glyceryl tributyrate is between 8.0 and 8.5; the activation energy was calculated to be 8.7 kcal x mol-1 (36.4 kJ/mol). Its substrate specificity is mainly directed against esters of glycerol and of primary monoalcohols. Similarly to pancreatic lipase but contrary to liver esterase, it is inhibited by bile salts; relief of this inhibition by colipase is only observed for pancreatic lipase. The possible role of the glycerol-ester hydrolase in the absorption of short and of medium chain triglycerides is discussed."}
{"id": "PMID:12958", "title": "Acetyl-coenzyme-A carboxylase of Candida Lipolytica. 1. Purification and properties of the enzyme.", "content": "Acetyl-coenzyme-A carboxylase has been isolated in homogeneous form from Candida lipolytica. The homogeneity of the enzyme preparation is evidenced by analytical ultracentrifugation, dodecyl-sulfate-polyacrylamide gel electrophoresis and Ouchterlony double-diffusion analysis. The purified enzyme exhibits a specific activity of 8.0 U/mg protein at 25 degrees C and contains 1 mol biotin/263000 g protein. The sedimentation coefficient (S20,W) of the enzyme is 18 S. It has been shown by dodecyl-sulfate-polyacrylamide gel electrophoresis that the enzyme possesses only one kind of subunit with a molecular weight of 230000. This finding, together with the biotin content, indicates that the C. lipolytica enzyme has a highly integrated subunit structure. The C. lipolytica enzyme is very labile, but is stabilized by glycerol. The enzyme is markedly activated by poly(ethyleneglycol), the activation being due principally to a decrease in the Km values for substrates. Even in the presence of this activator, the Km value for acetyl-CoA of the C. lipolytica enzyme is much higher than that of the enzyme from Saccharomyces cerevisiae and animal tissues. The C. lipolytica enzyme, unlike the enzyme from animal tissues, is not activated by citrate.", "contents": "Acetyl-coenzyme-A carboxylase of Candida Lipolytica. 1. Purification and properties of the enzyme. Acetyl-coenzyme-A carboxylase has been isolated in homogeneous form from Candida lipolytica. The homogeneity of the enzyme preparation is evidenced by analytical ultracentrifugation, dodecyl-sulfate-polyacrylamide gel electrophoresis and Ouchterlony double-diffusion analysis. The purified enzyme exhibits a specific activity of 8.0 U/mg protein at 25 degrees C and contains 1 mol biotin/263000 g protein. The sedimentation coefficient (S20,W) of the enzyme is 18 S. It has been shown by dodecyl-sulfate-polyacrylamide gel electrophoresis that the enzyme possesses only one kind of subunit with a molecular weight of 230000. This finding, together with the biotin content, indicates that the C. lipolytica enzyme has a highly integrated subunit structure. The C. lipolytica enzyme is very labile, but is stabilized by glycerol. The enzyme is markedly activated by poly(ethyleneglycol), the activation being due principally to a decrease in the Km values for substrates. Even in the presence of this activator, the Km value for acetyl-CoA of the C. lipolytica enzyme is much higher than that of the enzyme from Saccharomyces cerevisiae and animal tissues. The C. lipolytica enzyme, unlike the enzyme from animal tissues, is not activated by citrate."}
{"id": "PMID:12959", "title": "Acetyl-coenzyme-A carboxylase of Candida lipolytica. 2. Regulation of cellular content and synthesis of the enzyme.", "content": "The level of acetyl-coenzyme-A carboxylase activity in Candida lipolytica undergoes large variations depending upon the carbon source on which the yeast is grown. Cells grown on n-alkanes or fatty acids exhibit a lower activity level than do cells grown on glucose. Among the n-alkanes and fatty acids tested, n-heptadecane, n-octadecane, oleic acid and linoleic acid reduce the enzyme activity to the lowest levels, which are 16-18% of the activity level in glucose-grown cells. Immunochemical titrations and Ouchterlony double-diffusion analysis with specific antibody as well as kinetic studies have indicated that the observed decrease in the level of acetyl-CoA carboxylase activity is due to a reduction in the cellular content of the enzyme. Furthermore, isotopic leucine incorporation studies with the use of the immunoprecipitation technique have demonstrated that the relative rate of synthesis of the enzyme in oleic-acid-grown cells is diminished to 12% of that in glucose-grown cells. Evidence has also been obtained to support the view that the enzyme in this yeast is not degraded at a rate high enough to contribute to the marked decrease in the cellular content of the enzyme. Thus, it is concluded that the reduction in acetyl-CoA carboxylase content in fatty-acid-grown cells is due to diminished synthesis of the enzyme.", "contents": "Acetyl-coenzyme-A carboxylase of Candida lipolytica. 2. Regulation of cellular content and synthesis of the enzyme. The level of acetyl-coenzyme-A carboxylase activity in Candida lipolytica undergoes large variations depending upon the carbon source on which the yeast is grown. Cells grown on n-alkanes or fatty acids exhibit a lower activity level than do cells grown on glucose. Among the n-alkanes and fatty acids tested, n-heptadecane, n-octadecane, oleic acid and linoleic acid reduce the enzyme activity to the lowest levels, which are 16-18% of the activity level in glucose-grown cells. Immunochemical titrations and Ouchterlony double-diffusion analysis with specific antibody as well as kinetic studies have indicated that the observed decrease in the level of acetyl-CoA carboxylase activity is due to a reduction in the cellular content of the enzyme. Furthermore, isotopic leucine incorporation studies with the use of the immunoprecipitation technique have demonstrated that the relative rate of synthesis of the enzyme in oleic-acid-grown cells is diminished to 12% of that in glucose-grown cells. Evidence has also been obtained to support the view that the enzyme in this yeast is not degraded at a rate high enough to contribute to the marked decrease in the cellular content of the enzyme. Thus, it is concluded that the reduction in acetyl-CoA carboxylase content in fatty-acid-grown cells is due to diminished synthesis of the enzyme."}
{"id": "PMID:12960", "title": "Isolation, subunit structure and properties of the ATP-dependent deoxyribonuclease of Bacillus subtilis. State of the protein in a mutant devoid of activity.", "content": "A prodcedure was developed for the purification of the ATP-dependent deoxyribonuclease of Bacillus subtilis 168. It comprises ammonium sulphate fractionation, Sephadex gel filtration, DEAE-cellulose chromatography and gel electrophoresis on a discontinuous polyacrylamide gradient. The enzyme has been obtained in a homogeneous state. Its molecular weight was estimated to be 270000 by disc electrophoresis. Dodecylsulfate-polyacrylamide gel electrophoresis showed the presence of five nonidentical subunits of the following molecular weights: 81000, 70000, 62000, 52500 and 42500. These values give 308000 as the molecular weight of the native enzyme. The pH optimum of the purified enzyme is 9.6. The optimal concentrations of Mg2+ and ATP for exonuclease activity on native B. subtilis DNA were determined. ATP-requirement for hydrolysis of single-stranded DNA is less strigent. The enzyme also possesses high DNA-dependent ATPase activity. The purification procedure was applied to extracts of a mutant devoid of activity for this enzyme (strain GSY 1290). A protein was isolated which is very similar to the active DNAase as regards electrophoretic mobility, reaction with specific antisera and size of four of the subunits. One subunit is missing (Mr 70000) and is replaced by a smaller polypeptide (Mr 565000). The latter results suggest that the mutant is affected in the genetic locus coding for the 70000-Mr subunit.", "contents": "Isolation, subunit structure and properties of the ATP-dependent deoxyribonuclease of Bacillus subtilis. State of the protein in a mutant devoid of activity. A prodcedure was developed for the purification of the ATP-dependent deoxyribonuclease of Bacillus subtilis 168. It comprises ammonium sulphate fractionation, Sephadex gel filtration, DEAE-cellulose chromatography and gel electrophoresis on a discontinuous polyacrylamide gradient. The enzyme has been obtained in a homogeneous state. Its molecular weight was estimated to be 270000 by disc electrophoresis. Dodecylsulfate-polyacrylamide gel electrophoresis showed the presence of five nonidentical subunits of the following molecular weights: 81000, 70000, 62000, 52500 and 42500. These values give 308000 as the molecular weight of the native enzyme. The pH optimum of the purified enzyme is 9.6. The optimal concentrations of Mg2+ and ATP for exonuclease activity on native B. subtilis DNA were determined. ATP-requirement for hydrolysis of single-stranded DNA is less strigent. The enzyme also possesses high DNA-dependent ATPase activity. The purification procedure was applied to extracts of a mutant devoid of activity for this enzyme (strain GSY 1290). A protein was isolated which is very similar to the active DNAase as regards electrophoretic mobility, reaction with specific antisera and size of four of the subunits. One subunit is missing (Mr 70000) and is replaced by a smaller polypeptide (Mr 565000). The latter results suggest that the mutant is affected in the genetic locus coding for the 70000-Mr subunit."}
{"id": "PMID:12961", "title": "The effect of endogenous phosphate on the H+/Mn2+ ratio and the state of Mn2+ in the mitochondrial matrix.", "content": "1. Kinetics and stoichiometry of H+ extrusion and reuptake and of Mn2+ uptake and release have been measured in respiring liver mitochondria in the absence of external added Pi. H+ and Mn2+ fluxes are parallel during aerobic cation uptake but not during uncoupler induced cation release. The H+/Mn2+ is 1.24. Addition of SH reagents, in concentrations inhibiting the Pi carrier, modifies the kinetics of H+ extrusion and of Mn2+ uptake and release. The slow phase of uncoupler induced Mn2+ release is diminished. The H+/Mn2+ is increased to 1.72. Addition of SH reagents, after the phase of aerobic uptake is completed, results in a significant reduction of the extent of uncoupler-induced Mn2+ release. The extent of reuptake of endogenous Pi during aerobic uptake of Mn2+ is about 8 nmol x mg protein-1. 2. Aerobic uptake of Mn2+ in the absence of external Pi results in an electron spin resonance spectrum which is the sum of two components. One, denoted as S, corresponds to Mn(H2O)2+(6). Another denoted as E, reflects spin exchange narrowing. In contrast to previous claims the following evidence suggests that the spin exchange component is due to Mn3(PO4)2 precipitate: (a) the dimension of the spin exchange spectrum is markedly reduced by abolition of Pi transport; (b) the spin exchange spectrum is released very slowly by addition of uncouplers under conditions where uncouplers cause a rapid deenergization of mitochondria, reuptake of H+ and release of cations; (c) the free matrix Mn2+ is released slowly after addition of uncoupler if there is a large spin exchange signal; howeover the free matrix Mn2+ is abolished rapidly by uncoupler when formation of the spin exchange signal is prevented by pretreatment with Ca2+; (d) the band width of the spin exchange fraction is independent of the Mn2+/protein ratio either under kinetic or steady state conditions; (e) the experimental spectrum recalls closely that obtained by computer simulation by assuming it as a combination of Mn(H2O)2+(6) and Mn3(PO4)2. 3. It is concluded that endogenous Pi affects the process of aerobic divalent cation uptake. A part of Mn2+ uptake in the absence of externally added anions, consists of a Mn3(PO4)2 precipitate. This accounts for a H+/Mn2+ ratio lower than 2.", "contents": "The effect of endogenous phosphate on the H+/Mn2+ ratio and the state of Mn2+ in the mitochondrial matrix. 1. Kinetics and stoichiometry of H+ extrusion and reuptake and of Mn2+ uptake and release have been measured in respiring liver mitochondria in the absence of external added Pi. H+ and Mn2+ fluxes are parallel during aerobic cation uptake but not during uncoupler induced cation release. The H+/Mn2+ is 1.24. Addition of SH reagents, in concentrations inhibiting the Pi carrier, modifies the kinetics of H+ extrusion and of Mn2+ uptake and release. The slow phase of uncoupler induced Mn2+ release is diminished. The H+/Mn2+ is increased to 1.72. Addition of SH reagents, after the phase of aerobic uptake is completed, results in a significant reduction of the extent of uncoupler-induced Mn2+ release. The extent of reuptake of endogenous Pi during aerobic uptake of Mn2+ is about 8 nmol x mg protein-1. 2. Aerobic uptake of Mn2+ in the absence of external Pi results in an electron spin resonance spectrum which is the sum of two components. One, denoted as S, corresponds to Mn(H2O)2+(6). Another denoted as E, reflects spin exchange narrowing. In contrast to previous claims the following evidence suggests that the spin exchange component is due to Mn3(PO4)2 precipitate: (a) the dimension of the spin exchange spectrum is markedly reduced by abolition of Pi transport; (b) the spin exchange spectrum is released very slowly by addition of uncouplers under conditions where uncouplers cause a rapid deenergization of mitochondria, reuptake of H+ and release of cations; (c) the free matrix Mn2+ is released slowly after addition of uncoupler if there is a large spin exchange signal; howeover the free matrix Mn2+ is abolished rapidly by uncoupler when formation of the spin exchange signal is prevented by pretreatment with Ca2+; (d) the band width of the spin exchange fraction is independent of the Mn2+/protein ratio either under kinetic or steady state conditions; (e) the experimental spectrum recalls closely that obtained by computer simulation by assuming it as a combination of Mn(H2O)2+(6) and Mn3(PO4)2. 3. It is concluded that endogenous Pi affects the process of aerobic divalent cation uptake. A part of Mn2+ uptake in the absence of externally added anions, consists of a Mn3(PO4)2 precipitate. This accounts for a H+/Mn2+ ratio lower than 2."}
{"id": "PMID:12962", "title": "A pH-dependent interaction between histones H2A and H2B involving secondary and tertiary folding.", "content": "It has been shown by high-resolution proton magnetic resonance (PMR) spectroscopy and circular dichroism (CD) that an H2A/H2B histone complex exists after salt extraction of these histones from chromatin and that this complex can be fully renatured from both urea-denatured acid-extracted and from urea-denatured salt-extracted histones. The histone complex is shown to involve specific secondary and tertiary structure. Formation of this complex is observed to be critically dependent on pH, occurring at and above pH 5. It cannot be induced below pH 5 by increase in ionic strength. From CD spectra the H2A/H2B complex is shown to contain about 37% alpha helix but no beta structure, the latter being confirmed by infrared spectroscopy in the 6-mum region. The PMR spectra show that the structured region includes most of the aromatic residues of both histones, at least two histidine residues of H2B and probably histidines 31 and 82 of histone H2A. The secondary structure of histones H2A and H2B is predicted using the Chou and Fasman procedure and comparisons are made between the predictions for histones of different species. These results in conjunction with the experimental evidence lead to the conclusion that at least residues 31-95 of H2A and residues 37-114 of H2B, i.e. the more apolar regions of the molecules, are involved in the tertiary structure of the H2A/H2B complex.", "contents": "A pH-dependent interaction between histones H2A and H2B involving secondary and tertiary folding. It has been shown by high-resolution proton magnetic resonance (PMR) spectroscopy and circular dichroism (CD) that an H2A/H2B histone complex exists after salt extraction of these histones from chromatin and that this complex can be fully renatured from both urea-denatured acid-extracted and from urea-denatured salt-extracted histones. The histone complex is shown to involve specific secondary and tertiary structure. Formation of this complex is observed to be critically dependent on pH, occurring at and above pH 5. It cannot be induced below pH 5 by increase in ionic strength. From CD spectra the H2A/H2B complex is shown to contain about 37% alpha helix but no beta structure, the latter being confirmed by infrared spectroscopy in the 6-mum region. The PMR spectra show that the structured region includes most of the aromatic residues of both histones, at least two histidine residues of H2B and probably histidines 31 and 82 of histone H2A. The secondary structure of histones H2A and H2B is predicted using the Chou and Fasman procedure and comparisons are made between the predictions for histones of different species. These results in conjunction with the experimental evidence lead to the conclusion that at least residues 31-95 of H2A and residues 37-114 of H2B, i.e. the more apolar regions of the molecules, are involved in the tertiary structure of the H2A/H2B complex."}
{"id": "PMID:12963", "title": "Stopped-flow spectrophotometric characterization of enzymic reaction intermediates in the anaerobic reduction of pig-plasma benzylamine oxidase by amine substrates.", "content": "Reduction of benzylamine oxidase by p-methoxybenzylamine under anaerobic conditions leads to biphasic absorbance changes at 470 nm. These reflect the intermediate formation of an enzyme substrate complex with spectral properties different from those of native enzyme and fully reduced enzyme. The spectrally modified enzyme-substrate complex exhibits a broad difference absorption band centered around 360 nm. The transient accumulation of this intermediate during reaction can be conveniently followed by stopped-flow techniques at wavelengths between 320 and 360 nm, where contributions from the subsequent reduction of the enzymic 470-nm chromophore are of minor significance. 2. Analogous intermediates exhibiting similar absorption spectra seem to be formed on reduction of the enzyme by benzylamine and other amine substrates which were tested. Substitution of benzylamine as the reducing substrate by [alpha, alpha-2H]benzylamine results in a decreased accumulation of the spectrally modified intermediate. This indicates that its formation is preceded by deprotonation of the alpha-carbon of the amine substrate. 3. Circular dichroism spectra of benzylamine oxidase exhibit a positive band at 360 nm, lending support to the previous conclusion that benzylamine oxidase is a pyridoxal enzyme. Formation of the spectrally modified enzyme-substrate complex then most likely reflects the prototropic shift converting an amine-pyridoxal Schiff-base obtained by rapid pre-equilibration between enzyme and substrate into an aldehyde-pyridoxamine Schiff-base.", "contents": "Stopped-flow spectrophotometric characterization of enzymic reaction intermediates in the anaerobic reduction of pig-plasma benzylamine oxidase by amine substrates. Reduction of benzylamine oxidase by p-methoxybenzylamine under anaerobic conditions leads to biphasic absorbance changes at 470 nm. These reflect the intermediate formation of an enzyme substrate complex with spectral properties different from those of native enzyme and fully reduced enzyme. The spectrally modified enzyme-substrate complex exhibits a broad difference absorption band centered around 360 nm. The transient accumulation of this intermediate during reaction can be conveniently followed by stopped-flow techniques at wavelengths between 320 and 360 nm, where contributions from the subsequent reduction of the enzymic 470-nm chromophore are of minor significance. 2. Analogous intermediates exhibiting similar absorption spectra seem to be formed on reduction of the enzyme by benzylamine and other amine substrates which were tested. Substitution of benzylamine as the reducing substrate by [alpha, alpha-2H]benzylamine results in a decreased accumulation of the spectrally modified intermediate. This indicates that its formation is preceded by deprotonation of the alpha-carbon of the amine substrate. 3. Circular dichroism spectra of benzylamine oxidase exhibit a positive band at 360 nm, lending support to the previous conclusion that benzylamine oxidase is a pyridoxal enzyme. Formation of the spectrally modified enzyme-substrate complex then most likely reflects the prototropic shift converting an amine-pyridoxal Schiff-base obtained by rapid pre-equilibration between enzyme and substrate into an aldehyde-pyridoxamine Schiff-base."}
{"id": "PMID:12964", "title": "Proton equilibria in the binding of Zn2+ and of methylmercuric iodide to papain.", "content": "The proton liberation on the binding of zinc chloride and methylmercuric iodide to the (essential) thiol group of papain has been examined as a function of pH. This was carried out by (a) direct titration of the protons on the addition of the metal compound to active papain and (b) measurement of the extent of inhibition of enzyme activity by the metal compound as a function of pH. It was found that in the neutral pH range the thiol group or the neighbouring imidazole group in the free enzyme carries one proton, at low pH both groups do so, whereas at high pH neither group carries a proton. The pK values of the free enzyme that govern the proton release, 4.2 and 8.5, correspond to those that govern overall activity. Both from the experiments with methylmercuric iodide and from fluorescence measurements of methylmercuric papain, it was established that the imidazole group in the latter compound exhibits a pK of 5.4. Taking recent data into account, it was considered that the ion pair of thiolate anion and imidazolium cation, proposed by Polgar, is the best approximation to describe the charge distribution in the active centre and to explain the reaction mechanism.", "contents": "Proton equilibria in the binding of Zn2+ and of methylmercuric iodide to papain. The proton liberation on the binding of zinc chloride and methylmercuric iodide to the (essential) thiol group of papain has been examined as a function of pH. This was carried out by (a) direct titration of the protons on the addition of the metal compound to active papain and (b) measurement of the extent of inhibition of enzyme activity by the metal compound as a function of pH. It was found that in the neutral pH range the thiol group or the neighbouring imidazole group in the free enzyme carries one proton, at low pH both groups do so, whereas at high pH neither group carries a proton. The pK values of the free enzyme that govern the proton release, 4.2 and 8.5, correspond to those that govern overall activity. Both from the experiments with methylmercuric iodide and from fluorescence measurements of methylmercuric papain, it was established that the imidazole group in the latter compound exhibits a pK of 5.4. Taking recent data into account, it was considered that the ion pair of thiolate anion and imidazolium cation, proposed by Polgar, is the best approximation to describe the charge distribution in the active centre and to explain the reaction mechanism."}
{"id": "PMID:12965", "title": "Electron spin resonance investigations of mitochondrial electron transport in Neurospora crassa. Characterization of paramagnetic intermediates in a standard strain.", "content": "1. Submitochondrial particles from Neurospora strain inl-89601 have been analyzed by electron spin resonance spectroscopy (ESR). Numerous signals due to iron-sulfur proteins are observed at low temperatures. Analysis of these ESR signals at various temperatures allows the assignment of resonances to iron-sulfur centers 1-5 that have been described in other organisms. There are no discrepancies between the signals seen in Neurospora and those described in other organisms and it is likely that Neurospora mitochondria contain the same iron-sulfur centers that are observed elsewhere. 2. NADPH and NADH act to reduce the iron-sulfur centers of respiratory complex I. 3. The drug pyrrolnitrin [3-chloro-4-(2'-nitro-3'-chlorphenyl)pyrrole] is an effective inhibitor of both NADH-supported and succinate-supported electron transport in Neurospora. 4. Analysis of pyrrolnitrin inhibition curves, respiration studies, ESR spectra, and the steady-state level of reduction of cytochrome b in the presence and absence of the drug shows that pyrrolnitrin acts to inhibit electron transport in Neurospora mitochondria at multiple sites in the region between ubiquinone and cytochrome b.", "contents": "Electron spin resonance investigations of mitochondrial electron transport in Neurospora crassa. Characterization of paramagnetic intermediates in a standard strain. 1. Submitochondrial particles from Neurospora strain inl-89601 have been analyzed by electron spin resonance spectroscopy (ESR). Numerous signals due to iron-sulfur proteins are observed at low temperatures. Analysis of these ESR signals at various temperatures allows the assignment of resonances to iron-sulfur centers 1-5 that have been described in other organisms. There are no discrepancies between the signals seen in Neurospora and those described in other organisms and it is likely that Neurospora mitochondria contain the same iron-sulfur centers that are observed elsewhere. 2. NADPH and NADH act to reduce the iron-sulfur centers of respiratory complex I. 3. The drug pyrrolnitrin [3-chloro-4-(2'-nitro-3'-chlorphenyl)pyrrole] is an effective inhibitor of both NADH-supported and succinate-supported electron transport in Neurospora. 4. Analysis of pyrrolnitrin inhibition curves, respiration studies, ESR spectra, and the steady-state level of reduction of cytochrome b in the presence and absence of the drug shows that pyrrolnitrin acts to inhibit electron transport in Neurospora mitochondria at multiple sites in the region between ubiquinone and cytochrome b."}
{"id": "PMID:12966", "title": "Interaction of DNA with DNA-binding proteins. The characterization of protein HD from Escherichia coli and its nucleic acid complexes.", "content": "DNA-binding protein HD with a monomer molecular weight of 9000 was isolated from Escherichia coli cells. The protein occurs as a tetramer under native conditions and binds to single and double-stranded DNA and also to RNA. DNA complexed with protein HD is a poor template for DNA synthesis by E. coli polymerase I, II or III holoenzyme. Exonuclease III is hindered in degrading HD-protein-covered double-stranded DNA, whereas exonuclease I can digest complexed single-stranded DNA. Transcription is liqhtly stimulated in the presence of protein HD.", "contents": "Interaction of DNA with DNA-binding proteins. The characterization of protein HD from Escherichia coli and its nucleic acid complexes. DNA-binding protein HD with a monomer molecular weight of 9000 was isolated from Escherichia coli cells. The protein occurs as a tetramer under native conditions and binds to single and double-stranded DNA and also to RNA. DNA complexed with protein HD is a poor template for DNA synthesis by E. coli polymerase I, II or III holoenzyme. Exonuclease III is hindered in degrading HD-protein-covered double-stranded DNA, whereas exonuclease I can digest complexed single-stranded DNA. Transcription is liqhtly stimulated in the presence of protein HD."}
{"id": "PMID:12967", "title": "Kinetics of the interaction between aspartic aminotransferase and anions.", "content": "The kinetics of the interaction between deionized supernatant aspartic aminotransferase and various anions (cacodylate, phosphate and chloride) were studied by the temperature-jump technique. The anion concentration in the range covered by our experiments does not affect the transamination rate. On the other hand the conformational transition, recently observed at the active site of the enzyme, is hindered by an excess of anions. A single relaxation effect was observed at the enzyme chromophore wavelength in systems containing the aldimine form of the enzyme and the above anions. It is shown that this effect corresponds to the protonation of the chromophore. The relaxation times were of about 10 mus with phosphate, 20-100 mus with cacodylate and 1-2 ms with chloride. The pH and concentration dependence of this effect were studied. The fits of experimental data to a rate equations for various models were tested by a chi2 analysis. The best fit was obtained with models where anions bind rapidly to a site close to the chromophore, so that the pK of the chromophore is affected by anions binding. The rate of the observed relaxation considerably increased when the anion has buffering capacities; this indicates, in the case of cacodylate and phosphate, that the acidic component of the buffer directly exchanges a proton with the enzyme chromophore.", "contents": "Kinetics of the interaction between aspartic aminotransferase and anions. The kinetics of the interaction between deionized supernatant aspartic aminotransferase and various anions (cacodylate, phosphate and chloride) were studied by the temperature-jump technique. The anion concentration in the range covered by our experiments does not affect the transamination rate. On the other hand the conformational transition, recently observed at the active site of the enzyme, is hindered by an excess of anions. A single relaxation effect was observed at the enzyme chromophore wavelength in systems containing the aldimine form of the enzyme and the above anions. It is shown that this effect corresponds to the protonation of the chromophore. The relaxation times were of about 10 mus with phosphate, 20-100 mus with cacodylate and 1-2 ms with chloride. The pH and concentration dependence of this effect were studied. The fits of experimental data to a rate equations for various models were tested by a chi2 analysis. The best fit was obtained with models where anions bind rapidly to a site close to the chromophore, so that the pK of the chromophore is affected by anions binding. The rate of the observed relaxation considerably increased when the anion has buffering capacities; this indicates, in the case of cacodylate and phosphate, that the acidic component of the buffer directly exchanges a proton with the enzyme chromophore."}
{"id": "PMID:12968", "title": "Levansucrase of Bacillus subtilis. Characterization of a stabilized fructosyl-enzyme complex and identification of an aspartly residue as the binding site of the fructosyl group.", "content": "A covalently linked fructosyl-enzyme complex was isolated from a reaction mixture of enzyme and sucrose submitted to the quenching effect of a large decrease of the pH. The fructosyl-enzyme bond was shown to be stable under acidic and neutral conditions in the presence of high concentration of urea and of sodium dodecyl sulfate. This intermediate did not transfer at a measurable rate its fructosyl group to the usual fructosyl acceptors of the enzyme reaction under the usual conditions of enzyme activity. However stability measurements of the fructosyl-enzyme bond indicated a marked lability at pH values above 8.5. The apparent rate constant of the hydrolytic reaction of this bond evaluated under the standard state of molar concentration of hydroxide ion was of the same order of magnitude as the apparent rate constant of the hydrolytic reaction of the transient fructosyl-enzyme postulated from the kinetic analysis of levansucrase. Furthermore, nucleophilic agents like imidazole enhanced the hydrolytic reaction of the fructosyl-enzyme bond. Identification of the fructosyl binding site on the enzyme was accomplished by proteolytic hydrolysis of the trapped complex. Peptic digestion followed by pronase digestion released a fructosyl-aspartate compound that we have isolated in a high state of purity. The lability of the fructosyl-aspartate bond under mild alkaline conditions suggested that the fructosyl was linked through an ester bond involving the beta-carboxyl of the aspartate residue. Treatment of the trapped complex with cyanogen bromide released only one fructosylated peptide. The apparent molecular weight of this peptide was estimated to be lower than 10000.", "contents": "Levansucrase of Bacillus subtilis. Characterization of a stabilized fructosyl-enzyme complex and identification of an aspartly residue as the binding site of the fructosyl group. A covalently linked fructosyl-enzyme complex was isolated from a reaction mixture of enzyme and sucrose submitted to the quenching effect of a large decrease of the pH. The fructosyl-enzyme bond was shown to be stable under acidic and neutral conditions in the presence of high concentration of urea and of sodium dodecyl sulfate. This intermediate did not transfer at a measurable rate its fructosyl group to the usual fructosyl acceptors of the enzyme reaction under the usual conditions of enzyme activity. However stability measurements of the fructosyl-enzyme bond indicated a marked lability at pH values above 8.5. The apparent rate constant of the hydrolytic reaction of this bond evaluated under the standard state of molar concentration of hydroxide ion was of the same order of magnitude as the apparent rate constant of the hydrolytic reaction of the transient fructosyl-enzyme postulated from the kinetic analysis of levansucrase. Furthermore, nucleophilic agents like imidazole enhanced the hydrolytic reaction of the fructosyl-enzyme bond. Identification of the fructosyl binding site on the enzyme was accomplished by proteolytic hydrolysis of the trapped complex. Peptic digestion followed by pronase digestion released a fructosyl-aspartate compound that we have isolated in a high state of purity. The lability of the fructosyl-aspartate bond under mild alkaline conditions suggested that the fructosyl was linked through an ester bond involving the beta-carboxyl of the aspartate residue. Treatment of the trapped complex with cyanogen bromide released only one fructosylated peptide. The apparent molecular weight of this peptide was estimated to be lower than 10000."}
{"id": "PMID:12969", "title": "The dissociation of flavin coenzymes from trypsin-solubilized NADPH/Cytochrome c (P-450) reductase of pig-liver microsomes.", "content": "The change in fluorescence emission at 520 nm after excitation at 365 nm was used to investigate the effect of pH and ionic strength on the dissociation of flavin cofactors from microsomal NADPH/cytochrome c (P-450) reductase. In the unmodified enzyme both the FAD and FMN moieties appeared to dissociate at a similar rate and followed first-order kinetics. The rate constant for the dissociation was increased by low pH and high ionic strength, particularly in the range pH 4.4-3.8 (0.02 M acetate buffer) where the rate constants increased 80-fold. Modification of the enzyme by treatment with p-chloromercuribenzoate enhanced the rate of flavin dissociation and, in the region of pH 4, resulted in a biphasic increase in fluorescence consistent with two simultaneous parallel first-order dissociations. It was concluded that p-chloromercuribenzoate treatment modified the protein so that the two flavin cofactors dissociated at different rates. Using the measured rate constants for the dissociations, and the known variation in fluorescence of flavin nucleotides with pH, an analogue computer simulation of the dissociation as well as a manual curve-fitting procedure showed that the biphasic response could be explained as a simultaneous rapid dissociation of FAD and a slower loss of FMN from the protein.", "contents": "The dissociation of flavin coenzymes from trypsin-solubilized NADPH/Cytochrome c (P-450) reductase of pig-liver microsomes. The change in fluorescence emission at 520 nm after excitation at 365 nm was used to investigate the effect of pH and ionic strength on the dissociation of flavin cofactors from microsomal NADPH/cytochrome c (P-450) reductase. In the unmodified enzyme both the FAD and FMN moieties appeared to dissociate at a similar rate and followed first-order kinetics. The rate constant for the dissociation was increased by low pH and high ionic strength, particularly in the range pH 4.4-3.8 (0.02 M acetate buffer) where the rate constants increased 80-fold. Modification of the enzyme by treatment with p-chloromercuribenzoate enhanced the rate of flavin dissociation and, in the region of pH 4, resulted in a biphasic increase in fluorescence consistent with two simultaneous parallel first-order dissociations. It was concluded that p-chloromercuribenzoate treatment modified the protein so that the two flavin cofactors dissociated at different rates. Using the measured rate constants for the dissociations, and the known variation in fluorescence of flavin nucleotides with pH, an analogue computer simulation of the dissociation as well as a manual curve-fitting procedure showed that the biphasic response could be explained as a simultaneous rapid dissociation of FAD and a slower loss of FMN from the protein."}
{"id": "PMID:12970", "title": "Metabolism of gamma-glutamyl amino acids and peptides in mouse liver and kidney in vivo.", "content": "The metabolism in vivo of gamma-glutamyl amino acids and peptides was studied in the mouse after administration of loading doses of L-gamma-glutamyl-2-aminobutyrate and several other gamma-glutamyl compounds, including glutathione. A great and rapid accumulation of glutamate, glutamine, aspartate and pyrrolidone carboxylate was observed in the kidney. Similarly, after administration of a tracer dose of L-gamma-[14C]glutamyl-L-2-aminobutyrate a rapid incorporation of label into kidney glutamate, glutamine and aspartate was found. These results suggest that both the hydrolytic and gamma-glutamyl transfer reactions catalyzed by gamma-glutamyl transpeptidase are active in the renal handling of gamma-glutamyl compounds. Indirect evidence was obtained that L-gamma-glutamyl-2-aminobutyrate is partially taken up by the kidney cell in an intact form. In contrast to the kidney, administration of several gamma-glutamyl derivatives did not cause an increase in liver glutamate, glutamine and pyrrolidone carboxylate. After administration of L-gamma-glutamyl-2-aminobutyrate only a slight increase in liver aspartate and pyrrolidone carboxylate was observed. Experiments with L-gamma-[14C]glutamyl-L-2-aminobutyrate suggest that this derivative is largely first degraded to its component amino acids (probably in the kidney) before entering into the metabolism of the liver cell. gamma-Glutamyl transpeptidase may function in the metabolism and transport of glutathione and other gamma-glutamyl compounds in a manner analogous to the function of dipeptidases and disaccharidases in the metabolism and transport of dipeptides and disaccharides respectively.", "contents": "Metabolism of gamma-glutamyl amino acids and peptides in mouse liver and kidney in vivo. The metabolism in vivo of gamma-glutamyl amino acids and peptides was studied in the mouse after administration of loading doses of L-gamma-glutamyl-2-aminobutyrate and several other gamma-glutamyl compounds, including glutathione. A great and rapid accumulation of glutamate, glutamine, aspartate and pyrrolidone carboxylate was observed in the kidney. Similarly, after administration of a tracer dose of L-gamma-[14C]glutamyl-L-2-aminobutyrate a rapid incorporation of label into kidney glutamate, glutamine and aspartate was found. These results suggest that both the hydrolytic and gamma-glutamyl transfer reactions catalyzed by gamma-glutamyl transpeptidase are active in the renal handling of gamma-glutamyl compounds. Indirect evidence was obtained that L-gamma-glutamyl-2-aminobutyrate is partially taken up by the kidney cell in an intact form. In contrast to the kidney, administration of several gamma-glutamyl derivatives did not cause an increase in liver glutamate, glutamine and pyrrolidone carboxylate. After administration of L-gamma-glutamyl-2-aminobutyrate only a slight increase in liver aspartate and pyrrolidone carboxylate was observed. Experiments with L-gamma-[14C]glutamyl-L-2-aminobutyrate suggest that this derivative is largely first degraded to its component amino acids (probably in the kidney) before entering into the metabolism of the liver cell. gamma-Glutamyl transpeptidase may function in the metabolism and transport of glutathione and other gamma-glutamyl compounds in a manner analogous to the function of dipeptidases and disaccharidases in the metabolism and transport of dipeptides and disaccharides respectively."}
{"id": "PMID:12971", "title": "Effect of the immediate environment on the reactivity of the essential -SH group of papain.", "content": "The effect of the microenvironment on the reactivity of the essential -- SH group of papain was studied by alkylation with methyl iodide and with the more polar iodoacetamide. Rate and activation parameters for these reactions were determined with two forms of the -- SH group: the free mercaptide ion at pH 10.0, and the mercaptide-imidazolium ion-pair at pH 5.5. The ion-pair of papain reacts with methyl iodide at a rate 1470 times less than that of thiolsubtilisin. This surprising difference between the reactivities of the two enzymes suggests that in contrast to thiolsubtilisin, where a non-polar environment enhances the rate, in the case of papain a more polar environment somewhat inhibits the reaction with the non-polar methyl iodide. The positive activation entropy for the papain reaction may indicate an 'ordered' structure of bound water around the sulfur atom. The high rate and the low activation entropy (organized transition state) of the reaction of papain with iodoacetamide can be explained in terms of hydrogen-bond formation between the enzyme and the amide group of the alkylating agent.", "contents": "Effect of the immediate environment on the reactivity of the essential -SH group of papain. The effect of the microenvironment on the reactivity of the essential -- SH group of papain was studied by alkylation with methyl iodide and with the more polar iodoacetamide. Rate and activation parameters for these reactions were determined with two forms of the -- SH group: the free mercaptide ion at pH 10.0, and the mercaptide-imidazolium ion-pair at pH 5.5. The ion-pair of papain reacts with methyl iodide at a rate 1470 times less than that of thiolsubtilisin. This surprising difference between the reactivities of the two enzymes suggests that in contrast to thiolsubtilisin, where a non-polar environment enhances the rate, in the case of papain a more polar environment somewhat inhibits the reaction with the non-polar methyl iodide. The positive activation entropy for the papain reaction may indicate an 'ordered' structure of bound water around the sulfur atom. The high rate and the low activation entropy (organized transition state) of the reaction of papain with iodoacetamide can be explained in terms of hydrogen-bond formation between the enzyme and the amide group of the alkylating agent."}
{"id": "PMID:12972", "title": "Proton-nuclear-magnetic-resonance study of the conformation of neurotoxin II from Middle-Asian cobra (Naja naja oxiana) venom.", "content": "A proton nuclear magnetic resonance (NMR) study at 100 and 300 MHz of neurotoxin II from the venom of Middle-Asian cobra Naja naja oxiana has been performed in 2H2O and H2O solutions. By means of chemical modification and double resonance all the aromatic residue resonances have been assigned. From the NMR titration curves, pK values of histidine 4 and histidine 31 residues have been determined. For one of the two neighbouring tryptophan residues pH dependence (in the 2-8-pH range) of the chemical shifts of indole protons has been revealed. According to the different sensitivity of the linewidth of indole NH resonances to pH in H2O solution, the accessibility of each of the tryptophan residues has been estimated. Temperature dependence has been observed for the linewidth of the aromatic resonances of the tyrosine 24 residue. Deuterium exchange rates have been measured for amide protons as well as for C(2)H histidine resonances. The NMR data obtained have allowed the conclusions to be made that the two histidine residues and one of the tryptophan residues should be localized on the surface of the protein globule, that arginine residues should be present in the environment of histidine 4, that histidine 31 and the buried tryptophan are possibly localized in close spatial proximity and that the side chain of tyrosine 24 is buried within the protein globule.", "contents": "Proton-nuclear-magnetic-resonance study of the conformation of neurotoxin II from Middle-Asian cobra (Naja naja oxiana) venom. A proton nuclear magnetic resonance (NMR) study at 100 and 300 MHz of neurotoxin II from the venom of Middle-Asian cobra Naja naja oxiana has been performed in 2H2O and H2O solutions. By means of chemical modification and double resonance all the aromatic residue resonances have been assigned. From the NMR titration curves, pK values of histidine 4 and histidine 31 residues have been determined. For one of the two neighbouring tryptophan residues pH dependence (in the 2-8-pH range) of the chemical shifts of indole protons has been revealed. According to the different sensitivity of the linewidth of indole NH resonances to pH in H2O solution, the accessibility of each of the tryptophan residues has been estimated. Temperature dependence has been observed for the linewidth of the aromatic resonances of the tyrosine 24 residue. Deuterium exchange rates have been measured for amide protons as well as for C(2)H histidine resonances. The NMR data obtained have allowed the conclusions to be made that the two histidine residues and one of the tryptophan residues should be localized on the surface of the protein globule, that arginine residues should be present in the environment of histidine 4, that histidine 31 and the buried tryptophan are possibly localized in close spatial proximity and that the side chain of tyrosine 24 is buried within the protein globule."}
{"id": "PMID:12973", "title": "Magnetic studies on the ferri-haem undecapeptide of cytochrome c.", "content": "The pH-dependence of the magnetic moment of a ferri-haem undecapeptide, produced by peptic digestion of cytochrome c, has been measured in aqueous solution using a nuclear magnetic resonance method. Below pH 3 the magnetic moment is consistent with the presence of hydroxo-bridged dimers of high-spin iron(III). Above pH 7 the iron(III) is low-spin, the spin crossover conforming to a simple titration curve with pK 6.3 (n=1). This transition is discussed with reference to spectrophotometric studies of ligand binding at the haem.", "contents": "Magnetic studies on the ferri-haem undecapeptide of cytochrome c. The pH-dependence of the magnetic moment of a ferri-haem undecapeptide, produced by peptic digestion of cytochrome c, has been measured in aqueous solution using a nuclear magnetic resonance method. Below pH 3 the magnetic moment is consistent with the presence of hydroxo-bridged dimers of high-spin iron(III). Above pH 7 the iron(III) is low-spin, the spin crossover conforming to a simple titration curve with pK 6.3 (n=1). This transition is discussed with reference to spectrophotometric studies of ligand binding at the haem."}
{"id": "PMID:12974", "title": "Cyclic nucleotide hydrolysis in the thyroid gland. General properties and key role in the interrelations between concentrations of adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate.", "content": "Phosphodiesterase activities of horse (and dog) thyroid soluble fraction were compared with either cyclic AMP (adenosine 3':3'-monophosphate) or cyclic GMP (guanosine 3':5'-monophosphate) as substrate. Optimal activity for cyclic AMP hydrolysis was observed at pH 8, and at pH 7.6 for cyclic GMP. Increasing concentrations of ethyleneglycol bis(2-aminoethyl)-N,N'-tetraacetic acid inhibited both phosphodiesterase activities; in the presence of exogenous Ca2+, this effect was shifted to higher concentrations of the chelator. In a dialysed supernatant preparation, Ca2+ had no significant stimulatory effect, but both Mg2+ and Mn2+ increased cyclic nucleotides breakdown. Mn2+ promoted the hydrolysis of cyclic AMP more effectively than that of cyclic GMP. For both substrates, substrate velocity curves exhibited a two-slope pattern in a Hofstee plot. Cyclic GMP stimulated cyclic AMP hydrolysis, both nucleotides being at micromolar concentrations. Conversely, at no concentration had cyclic AMP any stimulatory effect on cyclic  GMP hydrolysis. 1-Methyl-3-isobutylxanthine and theophylline blocked the activation by cyclic GMP of cyclic GMP of cyclic AMP hydrolysis, whereas Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), a non-methylxanthine inhibitor of phosphodiesterases, did not alter this effect. In dog thyroid slices, carbamoylcholine, which promotes an accumulation of cyclic GMP, inhibits the thyrotropin-induced increase in cyclic AMP. This inhibitory effect of carbamoylcholine was blocked by theophylline and 1-methyl-3-isobutylxanthine, but not by Ro 20-1724. It is suggested that the cholinergic inhibitory effect on cyclic AMP accumulation is mediated by cyclic GMP, through a direct activation of phosphodiesterase activity.", "contents": "Cyclic nucleotide hydrolysis in the thyroid gland. General properties and key role in the interrelations between concentrations of adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate. Phosphodiesterase activities of horse (and dog) thyroid soluble fraction were compared with either cyclic AMP (adenosine 3':3'-monophosphate) or cyclic GMP (guanosine 3':5'-monophosphate) as substrate. Optimal activity for cyclic AMP hydrolysis was observed at pH 8, and at pH 7.6 for cyclic GMP. Increasing concentrations of ethyleneglycol bis(2-aminoethyl)-N,N'-tetraacetic acid inhibited both phosphodiesterase activities; in the presence of exogenous Ca2+, this effect was shifted to higher concentrations of the chelator. In a dialysed supernatant preparation, Ca2+ had no significant stimulatory effect, but both Mg2+ and Mn2+ increased cyclic nucleotides breakdown. Mn2+ promoted the hydrolysis of cyclic AMP more effectively than that of cyclic GMP. For both substrates, substrate velocity curves exhibited a two-slope pattern in a Hofstee plot. Cyclic GMP stimulated cyclic AMP hydrolysis, both nucleotides being at micromolar concentrations. Conversely, at no concentration had cyclic AMP any stimulatory effect on cyclic  GMP hydrolysis. 1-Methyl-3-isobutylxanthine and theophylline blocked the activation by cyclic GMP of cyclic GMP of cyclic AMP hydrolysis, whereas Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), a non-methylxanthine inhibitor of phosphodiesterases, did not alter this effect. In dog thyroid slices, carbamoylcholine, which promotes an accumulation of cyclic GMP, inhibits the thyrotropin-induced increase in cyclic AMP. This inhibitory effect of carbamoylcholine was blocked by theophylline and 1-methyl-3-isobutylxanthine, but not by Ro 20-1724. It is suggested that the cholinergic inhibitory effect on cyclic AMP accumulation is mediated by cyclic GMP, through a direct activation of phosphodiesterase activity."}
{"id": "PMID:12975", "title": "On the optical activity of ionized tyrosyl residues in ovine lutropin.", "content": "The effect of alkali on the circular dichroic (CD) spectra of ovine lutropin and its subunits has been studied. Mild alkaline pH induces the appearance of a new optically active band in the 250-nm region of the spectra of lutropin without any detectable alteration in the secondary structure of the protein. This change is reversible and can be correlated with ionization of 2--3 exposed tyrosyl residues in the intact hormone. In a previous report from this laboratory it was concluded that the three exposed tyrosyl residues are located in the alpha subunit, in positions 21, 92 and 93 [Burleigh, B.D., Liu, W.-K, and Ward, D.M. (1976) J. Biol. Chem. 251, 308--315]. Nitration of these residues lowers the pH at which the intensity of the 250-nm band is maximal. The importance of the tyrosyl residues of lutropin alpha (as opposed to those of lutropin beta) is also supported by the similarity of the effect of alkali on the CD spectra of lutropin and lutropin alpha. Further evidence for this involvement was also obtained by a comparison of the alkali-induced changes of refolded lutropin (alpha + beta recombinant) and the product obtained by recombination of des-(92--96)-lutropin alpha (obtained from carboxypeptidase treatment of the alpha-subunit) and lutropin beta. The results indicate that removal of tyrosines alpha 92 and alpha 93 results in a decrease of the intensity of the 235-nm band of ovine lutropin (at pH7.5) as well as that of the 250-nm band observed under alkaline conditions. It is therefore concluded that the 250-nm band observed in alkaline solutions of lutropin arises (at least partially) from the red shift produced in the short-wavelength optically active band of tyrosines alpha 21, alpha 92, and alpha 93 upon ionization.", "contents": "On the optical activity of ionized tyrosyl residues in ovine lutropin. The effect of alkali on the circular dichroic (CD) spectra of ovine lutropin and its subunits has been studied. Mild alkaline pH induces the appearance of a new optically active band in the 250-nm region of the spectra of lutropin without any detectable alteration in the secondary structure of the protein. This change is reversible and can be correlated with ionization of 2--3 exposed tyrosyl residues in the intact hormone. In a previous report from this laboratory it was concluded that the three exposed tyrosyl residues are located in the alpha subunit, in positions 21, 92 and 93 [Burleigh, B.D., Liu, W.-K, and Ward, D.M. (1976) J. Biol. Chem. 251, 308--315]. Nitration of these residues lowers the pH at which the intensity of the 250-nm band is maximal. The importance of the tyrosyl residues of lutropin alpha (as opposed to those of lutropin beta) is also supported by the similarity of the effect of alkali on the CD spectra of lutropin and lutropin alpha. Further evidence for this involvement was also obtained by a comparison of the alkali-induced changes of refolded lutropin (alpha + beta recombinant) and the product obtained by recombination of des-(92--96)-lutropin alpha (obtained from carboxypeptidase treatment of the alpha-subunit) and lutropin beta. The results indicate that removal of tyrosines alpha 92 and alpha 93 results in a decrease of the intensity of the 235-nm band of ovine lutropin (at pH7.5) as well as that of the 250-nm band observed under alkaline conditions. It is therefore concluded that the 250-nm band observed in alkaline solutions of lutropin arises (at least partially) from the red shift produced in the short-wavelength optically active band of tyrosines alpha 21, alpha 92, and alpha 93 upon ionization."}
{"id": "PMID:12976", "title": "Kinetics and regulation of sarcoplasmic reticulum ATPase.", "content": "The measurement of ATP binding to the sarcoplasmic reticulum membrane reveals that the calcium pump possesses one high affinity (Kd = 2--3 muM) site. Competition with substrate analogs show the high specifity of that site. At high ATP concentration another class of site can be detected with a much higher dissociation constant (Kd approximately 500 muM). This class of sites is of low specificity and ATP is easily displaced by other polyphosphates. The steady state rate of ATP cleavage is measured in the presence of ATP analogs. It is shown that the catalysis is due to the high affinity site. The activation of the hydrolysis rate at high substrate concentration may be related to the effect of binding of ATP to the weak sites. The effect of ATP analogs for various ATP concentration supports this hypothesis.", "contents": "Kinetics and regulation of sarcoplasmic reticulum ATPase. The measurement of ATP binding to the sarcoplasmic reticulum membrane reveals that the calcium pump possesses one high affinity (Kd = 2--3 muM) site. Competition with substrate analogs show the high specifity of that site. At high ATP concentration another class of site can be detected with a much higher dissociation constant (Kd approximately 500 muM). This class of sites is of low specificity and ATP is easily displaced by other polyphosphates. The steady state rate of ATP cleavage is measured in the presence of ATP analogs. It is shown that the catalysis is due to the high affinity site. The activation of the hydrolysis rate at high substrate concentration may be related to the effect of binding of ATP to the weak sites. The effect of ATP analogs for various ATP concentration supports this hypothesis."}
{"id": "PMID:12977", "title": "Ligand-dependent Bohr effect of Chrionomus hemoglobins.", "content": "The O2 and CO Bohr effects of monomeric and dimeric hemoglobins of the insect Chironomus thummi thummi were determined as proton releases upon ligation. For the O2 Bohr effect of the monomeric hemoglobin III a maximum value of 0.20 H+/heme was obtained at pH 7.5. Upon ligation with CO, however, only 0.04 H+/heme were released at the same pH. In agreement with this finding isoelectric focusing experiments revealed different isoelectric points for O2-liganded and CO-liganded states of hemoglobin III. Analogous results were obtained in the cases of the monomeric hemoglobin IV and the dimeric hemoglobins of Chironomus thummi thummi; here O2 Bohr effects of 0.43 and 0.86 H+/heme were observed. For the corresponding CO Bohr effects values of 0.08 and 0.31 H+/heme were obtained respectively. On the basis of the available structural data the reduced CO Bohr effect in hemoglobin III is discussed as arising from a steric hindrance of the CO ligand by the side chain of isoleucine-E11, obstructing the movement of the heme-iron upon reaction with carbon monoxide. It should, however, be noted that ligands, according to their different electron donor and acceptor properties, may generally induce different conformational changes and thus different Bohr effects, in those hemoglobins in which distinct tertiary and/or quaternary constraints have not evolved. The general utilization of CO instead of O2 as allosteric effector is ruled out by the results reported here.", "contents": "Ligand-dependent Bohr effect of Chrionomus hemoglobins. The O2 and CO Bohr effects of monomeric and dimeric hemoglobins of the insect Chironomus thummi thummi were determined as proton releases upon ligation. For the O2 Bohr effect of the monomeric hemoglobin III a maximum value of 0.20 H+/heme was obtained at pH 7.5. Upon ligation with CO, however, only 0.04 H+/heme were released at the same pH. In agreement with this finding isoelectric focusing experiments revealed different isoelectric points for O2-liganded and CO-liganded states of hemoglobin III. Analogous results were obtained in the cases of the monomeric hemoglobin IV and the dimeric hemoglobins of Chironomus thummi thummi; here O2 Bohr effects of 0.43 and 0.86 H+/heme were observed. For the corresponding CO Bohr effects values of 0.08 and 0.31 H+/heme were obtained respectively. On the basis of the available structural data the reduced CO Bohr effect in hemoglobin III is discussed as arising from a steric hindrance of the CO ligand by the side chain of isoleucine-E11, obstructing the movement of the heme-iron upon reaction with carbon monoxide. It should, however, be noted that ligands, according to their different electron donor and acceptor properties, may generally induce different conformational changes and thus different Bohr effects, in those hemoglobins in which distinct tertiary and/or quaternary constraints have not evolved. The general utilization of CO instead of O2 as allosteric effector is ruled out by the results reported here."}
{"id": "PMID:12978", "title": "Lysozyme from the insect Ceratitis capitata eggs.", "content": "1. Lysozyme from eggs of the Dipterous Ceratitis capitata (Wiedeman) has been purified by ion-exchange chromatography and gel filtration and its physicochemical properties have been investigated. This is the first insect lysozyme characterized so far and it exhibits some properties different to those described for other animal lysozymes. 2. Lysozyme from the insect eggs has a molecular weight of about 23200 and a sedimentation coefficient of 2.4 S. Molecular weight determination by sodium dedecylsulphate gel electrophoresis indicates that the molecule consists of a single polypeptide chain. 3. This lysozyme preparation shows notable stability at acidic pH values and lability at alkline pH values. It shows a single optimum pH at about 6.5.4. Chitinase/muramidase specific activity ratio is around 350 times higher for the insect lysozyme than for the hen egg-white enzyme. 5. The amino-acid composition shows the presence of one tryptophan residue per molecule of enzyme. This fact differentiates the lysozyme from insect eggs from other animal and plant lysozymes. From the amino acid composition, the absorption coefficient and the partial specific volume are calculated. 6. Glycine is the N-terminal residue.", "contents": "Lysozyme from the insect Ceratitis capitata eggs. 1. Lysozyme from eggs of the Dipterous Ceratitis capitata (Wiedeman) has been purified by ion-exchange chromatography and gel filtration and its physicochemical properties have been investigated. This is the first insect lysozyme characterized so far and it exhibits some properties different to those described for other animal lysozymes. 2. Lysozyme from the insect eggs has a molecular weight of about 23200 and a sedimentation coefficient of 2.4 S. Molecular weight determination by sodium dedecylsulphate gel electrophoresis indicates that the molecule consists of a single polypeptide chain. 3. This lysozyme preparation shows notable stability at acidic pH values and lability at alkline pH values. It shows a single optimum pH at about 6.5.4. Chitinase/muramidase specific activity ratio is around 350 times higher for the insect lysozyme than for the hen egg-white enzyme. 5. The amino-acid composition shows the presence of one tryptophan residue per molecule of enzyme. This fact differentiates the lysozyme from insect eggs from other animal and plant lysozymes. From the amino acid composition, the absorption coefficient and the partial specific volume are calculated. 6. Glycine is the N-terminal residue."}
{"id": "PMID:12979", "title": "Transport of cyclitols by a proton symport in Klebsiella aerogenes.", "content": "The respiration and the ATP content of Klebsiella aerogenes in the presence of various inhibitors were compared to the transport of scyllo-inositol. The ATPase was found to be inhibited by dicyclohexyl carbodiimide. The transport has been tested in anaerobiosis and aerobiosis. From the results obtained it is concluded that either ATP or respiration can sustain the transport activity in independent manner. 2. The energy derived from the respiratory chain reactions or the ATP hydrolysis results in electrogenic extrusion of protons. The electrochemical potential created drives the accumulation of scyllo-inositol, as shown by an increase of pH of the medium on addition of the substrate to cells in anaerobiosis. With non-induced cells no change in pH occurs, which demonstrates that proton flow is really linked to the transport. No H+/Na+ or K+ exchange is observed and the proton conductor carbonylcyanide m-chlorophenylhydrazone abolishes the pH shift caused by substrate addition. The stoichiometry of the symport H+/cyclitol is 1 and the half-maximum value of the pH variation as a function of the amount of scyllo-inositol added corresponds to a concentration of scyllo-inositol very close to the KT of influx.", "contents": "Transport of cyclitols by a proton symport in Klebsiella aerogenes. The respiration and the ATP content of Klebsiella aerogenes in the presence of various inhibitors were compared to the transport of scyllo-inositol. The ATPase was found to be inhibited by dicyclohexyl carbodiimide. The transport has been tested in anaerobiosis and aerobiosis. From the results obtained it is concluded that either ATP or respiration can sustain the transport activity in independent manner. 2. The energy derived from the respiratory chain reactions or the ATP hydrolysis results in electrogenic extrusion of protons. The electrochemical potential created drives the accumulation of scyllo-inositol, as shown by an increase of pH of the medium on addition of the substrate to cells in anaerobiosis. With non-induced cells no change in pH occurs, which demonstrates that proton flow is really linked to the transport. No H+/Na+ or K+ exchange is observed and the proton conductor carbonylcyanide m-chlorophenylhydrazone abolishes the pH shift caused by substrate addition. The stoichiometry of the symport H+/cyclitol is 1 and the half-maximum value of the pH variation as a function of the amount of scyllo-inositol added corresponds to a concentration of scyllo-inositol very close to the KT of influx."}
{"id": "PMID:12980", "title": "Tissue adhesives: their use in urology.", "content": "Tissue adhesives have certain advantages and should be used only for nephropexy and urethropexy but not for orchiopexy. Because of possible incrustation it should be avoided in the urinary collecting system.", "contents": "Tissue adhesives: their use in urology. Tissue adhesives have certain advantages and should be used only for nephropexy and urethropexy but not for orchiopexy. Because of possible incrustation it should be avoided in the urinary collecting system."}
{"id": "PMID:12983", "title": "Acute hypotensive effect of combined beta1-adrenoceptor blockade and beta2-adrenoceptor stimulation in spontaneously hypertensive rats (SHR).", "content": "The effect on heart rate (HR) and blood pressure (BP) of metoprolol, propranolol and terbutaline, applied alone or in combinations was studied in spontaneously hypertensive rats. Terbutaline had little effect on BP and HR. Propranolol combined with terbutaline had no effect while metoprolol combined with terbutaline decreased BP by 48 mm Hg without affecting HR. Thus the beta2-mediated increase in peripheral vascular resistance after terbutaline was revealed by a drop in BP after beta1-blockade by metoprolol, but not when both beta1-and beta2-receptors were blocked by propranolol.", "contents": "Acute hypotensive effect of combined beta1-adrenoceptor blockade and beta2-adrenoceptor stimulation in spontaneously hypertensive rats (SHR). The effect on heart rate (HR) and blood pressure (BP) of metoprolol, propranolol and terbutaline, applied alone or in combinations was studied in spontaneously hypertensive rats. Terbutaline had little effect on BP and HR. Propranolol combined with terbutaline had no effect while metoprolol combined with terbutaline decreased BP by 48 mm Hg without affecting HR. Thus the beta2-mediated increase in peripheral vascular resistance after terbutaline was revealed by a drop in BP after beta1-blockade by metoprolol, but not when both beta1-and beta2-receptors were blocked by propranolol."}
{"id": "PMID:12984", "title": "Iontophoretic studies of histamine and histamine antagonists in the feline vestibular nuclei.", "content": "The activity of single neurons in the vestibular neuronal complex of midcollicular decerebrate, decerebellectomized cats were recorded and their responsiveness to iontophoretically applied histamine and other agents determined. The majority of the cells tested were inhibited by iontophoresis of histamine while 24% were excited by this agent. Neurons exhibiting inhibitory responses were widely distributed throughout the four vestibular nuclei and adjacent reticular formation whereas excitatory responses to histamine were obtained mainly in the region of the lateral vestibular nucleus. The H2-receptor blocking agents metiamide and cimetidine were examined as to their actions on spontaneously firing cells and cells affected by histamine. Metiamide was selective in blocking histamine-induced inhibition but not excitation while cimetidine was ineffective in blocking either response. These results suggest that histamine has both inhibitory and excitatory actions on brain stem neurons and metiamide is an effective antagonist of histamine-induced inhibition.", "contents": "Iontophoretic studies of histamine and histamine antagonists in the feline vestibular nuclei. The activity of single neurons in the vestibular neuronal complex of midcollicular decerebrate, decerebellectomized cats were recorded and their responsiveness to iontophoretically applied histamine and other agents determined. The majority of the cells tested were inhibited by iontophoresis of histamine while 24% were excited by this agent. Neurons exhibiting inhibitory responses were widely distributed throughout the four vestibular nuclei and adjacent reticular formation whereas excitatory responses to histamine were obtained mainly in the region of the lateral vestibular nucleus. The H2-receptor blocking agents metiamide and cimetidine were examined as to their actions on spontaneously firing cells and cells affected by histamine. Metiamide was selective in blocking histamine-induced inhibition but not excitation while cimetidine was ineffective in blocking either response. These results suggest that histamine has both inhibitory and excitatory actions on brain stem neurons and metiamide is an effective antagonist of histamine-induced inhibition."}
{"id": "PMID:12985", "title": "Comparison of adiphenine and TRH effects on TSH release by rat pituitary in vitro.", "content": "The mechanism of action of adiphenine on in vitro rat anterior pituitary TSH release was compared to that of the physiological stimulator TRH. The comparative study showed that adiphenine and TRH were able to increase TSH release in a dose-dependent manner, had similar time courses of action for equipotent stimulating concentrations and produced similar aspects of stimulated TSH cells. However, there were several differences between the effects of adiphenine and TRH. Adiphenine action was inhibited by 20 mM K+; was not calcium dependent; was inhibited by neither thyroid hormones nor somatostatin; was little affected by energy depression. It is concluded that adiphenine probably acts near the ultimate steps of the TSH release pathway and could be a useful pharmacological tool for studying the mechanism of TSH release.", "contents": "Comparison of adiphenine and TRH effects on TSH release by rat pituitary in vitro. The mechanism of action of adiphenine on in vitro rat anterior pituitary TSH release was compared to that of the physiological stimulator TRH. The comparative study showed that adiphenine and TRH were able to increase TSH release in a dose-dependent manner, had similar time courses of action for equipotent stimulating concentrations and produced similar aspects of stimulated TSH cells. However, there were several differences between the effects of adiphenine and TRH. Adiphenine action was inhibited by 20 mM K+; was not calcium dependent; was inhibited by neither thyroid hormones nor somatostatin; was little affected by energy depression. It is concluded that adiphenine probably acts near the ultimate steps of the TSH release pathway and could be a useful pharmacological tool for studying the mechanism of TSH release."}
{"id": "PMID:12986", "title": "Perlapine and dopamine metabolism: prediction of antipsychotic efficacy.", "content": "A model for the prediction of antipsychotic efficacy based on the dose-dependent increase in levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum and tuberculum olfactorium of the rat is presented. The effect of perlapine, a sleep-promoting and sedative agent reported to lack antipsychotic efficacy, was compared in this system to haloperidol, chlorpromazine and clozapine. All four drugs produced a dose-dependent increase in DOPAC in the two dopamine-rich structures. The potency of perlapine was similar to that of chlorpromazine. Dopamine, assayed in the striatum and tuberculum olfactorium by a new gas chromatographic procedure was not altered by perlapine. The time--action curves for perlapine and clozapine were virtually identical both in the striatum and in the tuberculum olfactorium. All four drugs also elevated homovanillic acid to a similar extent. These results indicate that perlapine should be re-evaluated clinically. We predict that such trials will reveal that perlapine does possess antipsychotic efficacy.", "contents": "Perlapine and dopamine metabolism: prediction of antipsychotic efficacy. A model for the prediction of antipsychotic efficacy based on the dose-dependent increase in levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum and tuberculum olfactorium of the rat is presented. The effect of perlapine, a sleep-promoting and sedative agent reported to lack antipsychotic efficacy, was compared in this system to haloperidol, chlorpromazine and clozapine. All four drugs produced a dose-dependent increase in DOPAC in the two dopamine-rich structures. The potency of perlapine was similar to that of chlorpromazine. Dopamine, assayed in the striatum and tuberculum olfactorium by a new gas chromatographic procedure was not altered by perlapine. The time--action curves for perlapine and clozapine were virtually identical both in the striatum and in the tuberculum olfactorium. All four drugs also elevated homovanillic acid to a similar extent. These results indicate that perlapine should be re-evaluated clinically. We predict that such trials will reveal that perlapine does possess antipsychotic efficacy."}
{"id": "PMID:12988", "title": "Pharmacology of a new phthalane (Lu 10-171), with specific 5-HT uptake inhibiting properties.", "content": "The pharmacological profile of a new bicyclic substance, Lu 10-171 (1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitril), is described and compared with that of existing tricyclic thymoleptics. In mice and rats the compound exhibited marked 5-HT potentiating properties both in vivo and in vitro, being 5-10 times as active as chlorimipramine. The tests included 5-HT-, 5-HTP- and tryptophan-potentiation. In monoamine oxidase inhibitor treated dogs and rabbits the compound caused a marked hyperthermia. In rabbits this effect was completely blocked by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Hyperthermia induced by the central catecholamine displacing substance H 77/77 in rats was not affected by Lu 10-171, whereas the substance abolished the temperature rise induced by H 75/12. Reserpine- and tetrabenazine-induced ptosis and tetrabenazine-induced immobility in mice were antagonized by relatively low doses of existing tricyclic thymoleptics, whereas Lu 10-171 was very weak in this respect. Very weak in vitro anticholinergic and antihistaminergic properties were also registered for Lu 10-171. It is concluded that Lu 10-171 is a very potent and highly specific potentiator of 5-HT both in vivo and in vitro probably due to inhibition of 5-HT uptake. Thus this compound might be a useful agent in studying the role of 5-HT neurone systems in the control of mood. The substance does not possess the NA potentiating and anticholinergic and antihistaminergic properties characteristic of the tricyclic antidepressants.", "contents": "Pharmacology of a new phthalane (Lu 10-171), with specific 5-HT uptake inhibiting properties. The pharmacological profile of a new bicyclic substance, Lu 10-171 (1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitril), is described and compared with that of existing tricyclic thymoleptics. In mice and rats the compound exhibited marked 5-HT potentiating properties both in vivo and in vitro, being 5-10 times as active as chlorimipramine. The tests included 5-HT-, 5-HTP- and tryptophan-potentiation. In monoamine oxidase inhibitor treated dogs and rabbits the compound caused a marked hyperthermia. In rabbits this effect was completely blocked by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Hyperthermia induced by the central catecholamine displacing substance H 77/77 in rats was not affected by Lu 10-171, whereas the substance abolished the temperature rise induced by H 75/12. Reserpine- and tetrabenazine-induced ptosis and tetrabenazine-induced immobility in mice were antagonized by relatively low doses of existing tricyclic thymoleptics, whereas Lu 10-171 was very weak in this respect. Very weak in vitro anticholinergic and antihistaminergic properties were also registered for Lu 10-171. It is concluded that Lu 10-171 is a very potent and highly specific potentiator of 5-HT both in vivo and in vitro probably due to inhibition of 5-HT uptake. Thus this compound might be a useful agent in studying the role of 5-HT neurone systems in the control of mood. The substance does not possess the NA potentiating and anticholinergic and antihistaminergic properties characteristic of the tricyclic antidepressants."}
{"id": "PMID:12989", "title": "Effects of cimetidine and atropine sulfate on gastric secretion and healing of gastric and duodenal ulcers in rats.", "content": "Cimetidine, a new histamine H2-receptor antagonist (50 or 100 mg/kg) and atropine sulfate (15 mg/kg) given intraduodenally, markedly inhibited gastric secretion in pylorus-ligated rats. Cimetidine (100 or 200 mg/kg/day) given for 10 or 12 consecutive days orally in two divided doses, significantly promoted the healing rate of both gastric and duodenal ulcers induced in rats. Atropine (30 mg/kg/day) also significantly accelerated the healing of duodenal ulcers but failed to affect gastric ulcers.", "contents": "Effects of cimetidine and atropine sulfate on gastric secretion and healing of gastric and duodenal ulcers in rats. Cimetidine, a new histamine H2-receptor antagonist (50 or 100 mg/kg) and atropine sulfate (15 mg/kg) given intraduodenally, markedly inhibited gastric secretion in pylorus-ligated rats. Cimetidine (100 or 200 mg/kg/day) given for 10 or 12 consecutive days orally in two divided doses, significantly promoted the healing rate of both gastric and duodenal ulcers induced in rats. Atropine (30 mg/kg/day) also significantly accelerated the healing of duodenal ulcers but failed to affect gastric ulcers."}
{"id": "PMID:12990", "title": "Relaxation of coronary artery strips by adenosine and acidosis.", "content": "Cumulative dose-response curves of Ca2+-induced tension increments were studied in K+-depolarized helical strips of dog coronary arteries. Adenosine 10(-4) M reduced the Ca2+ sensitivity of the strips without altering the maximal tension with full Ca2+ activation. In contrast, acidosis of pH 7.05 significantly diminished the maximal tension with full Ca2+ activation. The relaxing effect of acidosis was almost completely abolished by 10(-4) M adenosine. It is concluded that adenosine inhibits Ca2+ influx, whereas acidosis depresses the contractile process of vascular smooth muscle directly.", "contents": "Relaxation of coronary artery strips by adenosine and acidosis. Cumulative dose-response curves of Ca2+-induced tension increments were studied in K+-depolarized helical strips of dog coronary arteries. Adenosine 10(-4) M reduced the Ca2+ sensitivity of the strips without altering the maximal tension with full Ca2+ activation. In contrast, acidosis of pH 7.05 significantly diminished the maximal tension with full Ca2+ activation. The relaxing effect of acidosis was almost completely abolished by 10(-4) M adenosine. It is concluded that adenosine inhibits Ca2+ influx, whereas acidosis depresses the contractile process of vascular smooth muscle directly."}
{"id": "PMID:12993", "title": "Red blood cell selection in chimeric mice.", "content": "Starch gel electrophoresis of a large number of tissues and organs from C3H in equilibrium C57BL aggregation chimeras suggests that the C57BL red blood cell population predominates, whereas for other tissues the proportions of the two components are more nearly equal. A similar predominance of (C57BL X C3H)F1 red blood cells is seen in (C57BL X C3H)F1 in equilibrium Recessive chimeras. Analysis of blood samples taken from the same animals at different times suggests that a temporal shift in the proportions of the two component red cell populations occurs in some adult chimeras and results in an unbalanced chimeric phenotype. It is suggested that differential mitotic activity contributes to strain-dependent, tissue-specific selection pressures in the erythropoietic tissue.", "contents": "Red blood cell selection in chimeric mice. Starch gel electrophoresis of a large number of tissues and organs from C3H in equilibrium C57BL aggregation chimeras suggests that the C57BL red blood cell population predominates, whereas for other tissues the proportions of the two components are more nearly equal. A similar predominance of (C57BL X C3H)F1 red blood cells is seen in (C57BL X C3H)F1 in equilibrium Recessive chimeras. Analysis of blood samples taken from the same animals at different times suggests that a temporal shift in the proportions of the two component red cell populations occurs in some adult chimeras and results in an unbalanced chimeric phenotype. It is suggested that differential mitotic activity contributes to strain-dependent, tissue-specific selection pressures in the erythropoietic tissue."}
{"id": "PMID:13002", "title": "Follow-up study of oral contraceptive acceptors in Howrah District in India.", "content": "In the Howrah District in India, three clinics--one in each of the urban, slum, and rural areas of the city--were initiated by the Humanity Association of Howrah in November of 1968 to supply oral contraceptives (OCs) to women from 15 to 45 years of age. The project was discontinued in September, 1972. Of the 1700 patients still active when the project ended, 1527 were contacted for the follow-up survey. Findings indicate that most women in this district were satisfied with OCs and would continue to use them if they were available. In corroboration of this, it was found that 43% of the women had used OC'S obtained from other sources after the project was discontinued. While 35.5% of the women who used no contraceptive method after project ended reported becoming pregnant or suspected that they were pregnant at the time of the interview, only 4.2% of those who reported using some form of contraception reported pregnancy or suspected pregnancy. The demographic impact of the project will be evaluated on the basis of data to be obtained in a subsequent survey of the same communities.", "contents": "Follow-up study of oral contraceptive acceptors in Howrah District in India. In the Howrah District in India, three clinics--one in each of the urban, slum, and rural areas of the city--were initiated by the Humanity Association of Howrah in November of 1968 to supply oral contraceptives (OCs) to women from 15 to 45 years of age. The project was discontinued in September, 1972. Of the 1700 patients still active when the project ended, 1527 were contacted for the follow-up survey. Findings indicate that most women in this district were satisfied with OCs and would continue to use them if they were available. In corroboration of this, it was found that 43% of the women had used OC'S obtained from other sources after the project was discontinued. While 35.5% of the women who used no contraceptive method after project ended reported becoming pregnant or suspected that they were pregnant at the time of the interview, only 4.2% of those who reported using some form of contraception reported pregnancy or suspected pregnancy. The demographic impact of the project will be evaluated on the basis of data to be obtained in a subsequent survey of the same communities."}
{"id": "PMID:13003", "title": "A comparison of flexible and nonflexible plastic cannulae for performing first trimester abortion.", "content": "The safety and effectiveness of flexible and nonflexible plastic cannulae used in vacuum aspiration abortion for patients at 6 to 12 weeks' gestation were evaluated in a study of 1100 physically healthy women in Ljublijana, Yugoslavia. To minimize study biases, each type of cannulae was randomly assigned to 550 patients. To minimize evaluator bias, a second physician who was kept unaware of which cannula was used for particular patient was responsible for evaluating patients after the procedures. Both groups of patients were similar with respect to age, parity, marital status, formal education and gestational age. Higher rates of retained tissue and cannula obstruction were obtained with the flexible cannula. The two types of cannulae were not significantly different with respect to other criteria of evaluation.", "contents": "A comparison of flexible and nonflexible plastic cannulae for performing first trimester abortion. The safety and effectiveness of flexible and nonflexible plastic cannulae used in vacuum aspiration abortion for patients at 6 to 12 weeks' gestation were evaluated in a study of 1100 physically healthy women in Ljublijana, Yugoslavia. To minimize study biases, each type of cannulae was randomly assigned to 550 patients. To minimize evaluator bias, a second physician who was kept unaware of which cannula was used for particular patient was responsible for evaluating patients after the procedures. Both groups of patients were similar with respect to age, parity, marital status, formal education and gestational age. Higher rates of retained tissue and cannula obstruction were obtained with the flexible cannula. The two types of cannulae were not significantly different with respect to other criteria of evaluation."}
{"id": "PMID:13004", "title": "Evaluation of trained midwives in a copper-T IUD insertion Program in Isfahan, Iran.", "content": "From four centers in Isfahan, data from 252 insertions of the Cu-T-200 made by midwives and 646 insertions of the same device made by doctors are compared. Although the net cumulative one-year continuation rate for women who had a copper-T inserted by a midwife is significantly lower than for women who had a copper-T inserted by a doctor there are no significant differences between the one-year event rates for the two groups of patients. These data suggest that an expanded role for midwives in IUD insertion programs would be an efficient use of health personnel.", "contents": "Evaluation of trained midwives in a copper-T IUD insertion Program in Isfahan, Iran. From four centers in Isfahan, data from 252 insertions of the Cu-T-200 made by midwives and 646 insertions of the same device made by doctors are compared. Although the net cumulative one-year continuation rate for women who had a copper-T inserted by a midwife is significantly lower than for women who had a copper-T inserted by a doctor there are no significant differences between the one-year event rates for the two groups of patients. These data suggest that an expanded role for midwives in IUD insertion programs would be an efficient use of health personnel."}
{"id": "PMID:13005", "title": "Herpes type-2 viruses and gynaecological malignancies.", "content": "Numerous sero-epidemiologic studies have noted an association between Herpes Type 2 (HT-2) virus and carcinoma of the cervix. In a study to evaluate the role of this virus, if any, on the etiology of extra cervical pelvic malignancies in Ibadan, the prevalence of HT-2 virus antibodies was found not to be significantly different in patients with extra cervical pelvic malignancies (carcinoma of the vulva and malignant trophoblastic disease) and cases of chronic cervicitis when compared with healthy controls. It was therefore concluded that no association could be found between HT-2 virus and extra cervical pelvic malignancies.", "contents": "Herpes type-2 viruses and gynaecological malignancies. Numerous sero-epidemiologic studies have noted an association between Herpes Type 2 (HT-2) virus and carcinoma of the cervix. In a study to evaluate the role of this virus, if any, on the etiology of extra cervical pelvic malignancies in Ibadan, the prevalence of HT-2 virus antibodies was found not to be significantly different in patients with extra cervical pelvic malignancies (carcinoma of the vulva and malignant trophoblastic disease) and cases of chronic cervicitis when compared with healthy controls. It was therefore concluded that no association could be found between HT-2 virus and extra cervical pelvic malignancies."}
{"id": "PMID:13006", "title": "Feto-maternal concentrations of diazepam and W-demethyldiazepam after intra-amniotic diazepam injection.", "content": "Ten milligrams of diazepam were injected intraamniotically in 8 mothers prior to therapeutic abortion between 12 and 19 weeks. The diazepam concentrations in the maternal plasma were comparable to those found after the same intramuscular diazepam dose to the mother. The concentration of diazepam in the amniotic fluid 12 to 18 hours after the injection was no longer significantly higher than in the maternal plasma. The concentrations of diazepam in the fetal plasma, liver and brain were comparable to the concentrations resulting from a 10 mg intramuscular diazepam dose to the mother about 2 hours before legal abortion. The feto-maternal ratio of diazepam was of same magnitude as after the intramuscular application to the mother. The results indicate that the disappearance of diazepam from the amniotic fluid in this stage of pregnancy occurs extraplacentally, through the mambranes into the uterine circulation. In the treatment of a fetus with drugs having properties similar to diazepam, intra-amniotic administration is no better than intramuscular administration to the mother.", "contents": "Feto-maternal concentrations of diazepam and W-demethyldiazepam after intra-amniotic diazepam injection. Ten milligrams of diazepam were injected intraamniotically in 8 mothers prior to therapeutic abortion between 12 and 19 weeks. The diazepam concentrations in the maternal plasma were comparable to those found after the same intramuscular diazepam dose to the mother. The concentration of diazepam in the amniotic fluid 12 to 18 hours after the injection was no longer significantly higher than in the maternal plasma. The concentrations of diazepam in the fetal plasma, liver and brain were comparable to the concentrations resulting from a 10 mg intramuscular diazepam dose to the mother about 2 hours before legal abortion. The feto-maternal ratio of diazepam was of same magnitude as after the intramuscular application to the mother. The results indicate that the disappearance of diazepam from the amniotic fluid in this stage of pregnancy occurs extraplacentally, through the mambranes into the uterine circulation. In the treatment of a fetus with drugs having properties similar to diazepam, intra-amniotic administration is no better than intramuscular administration to the mother."}
{"id": "PMID:13007", "title": "A comparison of laparoscopy and culdoscopy for internal sterilization.", "content": "In recent years, the increased demand for sterilization by women who have achieved their desired family size has emphasized the need to improve both existing methods of tubal occlusion and the means of access to the Fallopian tubes. Utilization of diagnostic instruments such as the laparoscope and culdoscope to perform sterilization minimizes the trauma associated with standard laparotomy and colpotomy and promises to reduce morbidity occurring as a result of sterilization. In order to evaluate and compare the improved techniques of laparoscopy and culdoscopy for elective interval sterilization, 722 women were studied between January and August of 1973 at the Siriraj Hospital in Bangkok. For 279 patients (Group I), sterilization was performed by culdoscopic tubal ligation using a modified Pomeroy technique; for 443 patients (Group II), the procedure used was laparoscopic tubal cauterization and cutting. All procedures were performed using local anesthesia on an outpatient basis. Complication rates and required surgical time were similar for both procedures and compared favorably with rates reported by other investigators. Because of a low incidence of complications and the elimination of the need for general anesthesia and hospitalization, both endoscopic procedures appear to be of particular value in developing countries where hospital facilities and physician time are in short supply.", "contents": "A comparison of laparoscopy and culdoscopy for internal sterilization. In recent years, the increased demand for sterilization by women who have achieved their desired family size has emphasized the need to improve both existing methods of tubal occlusion and the means of access to the Fallopian tubes. Utilization of diagnostic instruments such as the laparoscope and culdoscope to perform sterilization minimizes the trauma associated with standard laparotomy and colpotomy and promises to reduce morbidity occurring as a result of sterilization. In order to evaluate and compare the improved techniques of laparoscopy and culdoscopy for elective interval sterilization, 722 women were studied between January and August of 1973 at the Siriraj Hospital in Bangkok. For 279 patients (Group I), sterilization was performed by culdoscopic tubal ligation using a modified Pomeroy technique; for 443 patients (Group II), the procedure used was laparoscopic tubal cauterization and cutting. All procedures were performed using local anesthesia on an outpatient basis. Complication rates and required surgical time were similar for both procedures and compared favorably with rates reported by other investigators. Because of a low incidence of complications and the elimination of the need for general anesthesia and hospitalization, both endoscopic procedures appear to be of particular value in developing countries where hospital facilities and physician time are in short supply."}
{"id": "PMID:13008", "title": "Burkitt's lymphoma presenting during lactation.", "content": "The diagnostic difficulties and treatment failures of Burkitt's lymphoma manifesting during lactation are presented. All 5 cases presented as breast swelling, mimicking mastitis carcinomatosa; those patients actively lactating had fulminant disease, fatal within a few weeks. There was widespread involvement of internal organs. The importance of early correct diagnosis was emphasized and clinicians are alerted to the possibility of Burkitt's lymphoma occurring during lactation without jaw or abdominal presentation. Whether the fulminant manifestation of Burkitt's lymphoma occurring during lactation was coincidental or not, the possibility exists that a favourable milieu for the tumour growth might have been produced or the body immune mechanism lowered.", "contents": "Burkitt's lymphoma presenting during lactation. The diagnostic difficulties and treatment failures of Burkitt's lymphoma manifesting during lactation are presented. All 5 cases presented as breast swelling, mimicking mastitis carcinomatosa; those patients actively lactating had fulminant disease, fatal within a few weeks. There was widespread involvement of internal organs. The importance of early correct diagnosis was emphasized and clinicians are alerted to the possibility of Burkitt's lymphoma occurring during lactation without jaw or abdominal presentation. Whether the fulminant manifestation of Burkitt's lymphoma occurring during lactation was coincidental or not, the possibility exists that a favourable milieu for the tumour growth might have been produced or the body immune mechanism lowered."}
{"id": "PMID:13009", "title": "Polycystic ovaries. Presentation and response to wedge resection.", "content": "Polycystic ovarian disease has been recognised for quite a long time, although its presentations have varied from place to place. In a report of cases of polycystic ovaries seen in the University College Hospital, Ibadan, Nigeria, over a six-year period, it was shown that the syndrome of Stein-Leventhal identifies only a very small and probably artificial fraction of the much larger number of patients who actually have polycystic ovarian disease. It was further shown that the benefit derived from wedge resection in our cases was marked. Of the cases that were subsequently seen at follow-up, there was restoration of regular ovulatory menstrual flow in 83.3% and achievement of pregnancy in 33.3%. Hence, the observation that wedge resection is beneficial, and at times curative in polycystic ovarian disease seems to have a sound foundation.", "contents": "Polycystic ovaries. Presentation and response to wedge resection. Polycystic ovarian disease has been recognised for quite a long time, although its presentations have varied from place to place. In a report of cases of polycystic ovaries seen in the University College Hospital, Ibadan, Nigeria, over a six-year period, it was shown that the syndrome of Stein-Leventhal identifies only a very small and probably artificial fraction of the much larger number of patients who actually have polycystic ovarian disease. It was further shown that the benefit derived from wedge resection in our cases was marked. Of the cases that were subsequently seen at follow-up, there was restoration of regular ovulatory menstrual flow in 83.3% and achievement of pregnancy in 33.3%. Hence, the observation that wedge resection is beneficial, and at times curative in polycystic ovarian disease seems to have a sound foundation."}
{"id": "PMID:13010", "title": "Cervical pregnancy: report of three cases and a review of the literature.", "content": "Three cases of cervical pregnancy are reported and the literature is reviewed. The incidence is found to be increasing and it was felt to be related to the increasing number of legal or therapeutic abortions, or other surgical procedures on the cervix and endometrial cavity, resulting in unsuitable endometrium for implantation of a fertilized ovum.", "contents": "Cervical pregnancy: report of three cases and a review of the literature. Three cases of cervical pregnancy are reported and the literature is reviewed. The incidence is found to be increasing and it was felt to be related to the increasing number of legal or therapeutic abortions, or other surgical procedures on the cervix and endometrial cavity, resulting in unsuitable endometrium for implantation of a fertilized ovum."}
{"id": "PMID:13011", "title": "Pelvic actinomycosis.", "content": "Case report of tubo-ovarian abscess due to Actinomyces israeli is presented with revision of the literature with regard to pathogenesis, diagnostic difficulties and treatment. Diagnosis was established by culturing the organism from exudate obtained during surgery. The pathogenesis of pelvic actinomycosis is still controversial. Penetration of the GI tract with subsequent infection of the pelvic viscera seems to be the most likely mode of infection. Penicillin has an important role in the treatment of this disease. It does not cure, but retards the course of the infection. Surgical extirpation of infected tissue in combination with penicillin offers the best therapeutic results. When chronic pelvic inflammatory disease does not respond to therapy, when the sedimentation rate remains high, and the patient's general debility is progressive, an actinomycotic infection should be suspected.", "contents": "Pelvic actinomycosis. Case report of tubo-ovarian abscess due to Actinomyces israeli is presented with revision of the literature with regard to pathogenesis, diagnostic difficulties and treatment. Diagnosis was established by culturing the organism from exudate obtained during surgery. The pathogenesis of pelvic actinomycosis is still controversial. Penetration of the GI tract with subsequent infection of the pelvic viscera seems to be the most likely mode of infection. Penicillin has an important role in the treatment of this disease. It does not cure, but retards the course of the infection. Surgical extirpation of infected tissue in combination with penicillin offers the best therapeutic results. When chronic pelvic inflammatory disease does not respond to therapy, when the sedimentation rate remains high, and the patient's general debility is progressive, an actinomycotic infection should be suspected."}
{"id": "PMID:13012", "title": "Diagnosis of iron deficiency anaemia among Nigerian pregnant women by serum iron/T.I.B.C. determination.", "content": "Fifty-five patients have been investigated for anaemia in pregnancy. Using the serum iron/T.I.B.C. ratio as a diagnostic index it has been found that iron deficiency exists in 60% of our expectant mothers with mild anaemia. This type of anaemia was more common in multiparous women and more frequent in the first and second trimesters of pregnancy, There is, therefore, a strong indication for the routine administration of iron supplements to our women during pregnancy and the puerperium.", "contents": "Diagnosis of iron deficiency anaemia among Nigerian pregnant women by serum iron/T.I.B.C. determination. Fifty-five patients have been investigated for anaemia in pregnancy. Using the serum iron/T.I.B.C. ratio as a diagnostic index it has been found that iron deficiency exists in 60% of our expectant mothers with mild anaemia. This type of anaemia was more common in multiparous women and more frequent in the first and second trimesters of pregnancy, There is, therefore, a strong indication for the routine administration of iron supplements to our women during pregnancy and the puerperium."}
{"id": "PMID:13013", "title": "Lecithin/sphingomyelin ratio versus rapid surfactant test in normal and diabetic pregnancies.", "content": "Lecithin/sphingomyelin (L/S) ratio was measured and rapid surfactant test (RST) was performed on amniotic fluid samples drawn from 60 normal and 18 diabetic pregnancies, for determination of fetal lung maturity. The results were compared to the neonatal outcome. Comparison of L/S ratio and RST demonstrates a good correlation (95%) between the two tests in normal pregnancies. In diabetic pregnancies, however, correlation is notably lower (54%). Respiratory distress syndrome (RDS) was predicted in both L/S ratio and RST in 35-40% of normal pregnancies, with 60-65% of false negative results. In diabetic pregnancies the L/S ratio was as reliable as in normal pregnancies, but the RST was less reliable, with an RDS prediction rate of 18%. The assumption is made that increased amniotic fluid volume in diabetic pregnancies, results in dilution of the surfactant giving more false negative results in RST than are seen with L/S ratio, as in the latter, by measuring the ratio between the two constituents of amniotic fluid, the dilution factor is abolished. In diabetic pregnancies, a positive RST is reliable, but with negative results, L/S ratio must be determined for correct assessment of fetal lung maturity.", "contents": "Lecithin/sphingomyelin ratio versus rapid surfactant test in normal and diabetic pregnancies. Lecithin/sphingomyelin (L/S) ratio was measured and rapid surfactant test (RST) was performed on amniotic fluid samples drawn from 60 normal and 18 diabetic pregnancies, for determination of fetal lung maturity. The results were compared to the neonatal outcome. Comparison of L/S ratio and RST demonstrates a good correlation (95%) between the two tests in normal pregnancies. In diabetic pregnancies, however, correlation is notably lower (54%). Respiratory distress syndrome (RDS) was predicted in both L/S ratio and RST in 35-40% of normal pregnancies, with 60-65% of false negative results. In diabetic pregnancies the L/S ratio was as reliable as in normal pregnancies, but the RST was less reliable, with an RDS prediction rate of 18%. The assumption is made that increased amniotic fluid volume in diabetic pregnancies, results in dilution of the surfactant giving more false negative results in RST than are seen with L/S ratio, as in the latter, by measuring the ratio between the two constituents of amniotic fluid, the dilution factor is abolished. In diabetic pregnancies, a positive RST is reliable, but with negative results, L/S ratio must be determined for correct assessment of fetal lung maturity."}
{"id": "PMID:13014", "title": "Epidural analgesia in midtrimester abortion.", "content": "Epidural analgesia was performed in 78 women with abortion in the midtrimester or pre-term delivery of up to 27 weeks of pregnancy. The patients were divided into three groups. The first group included thirty women with signs of inevitable abortion. The second group comprised of 9 cases of induced abortion and the third one of 39 cases of pre-term delivery. The three groups were statistically evaluated in relation to time of abortion or labor, fetal weight, weeks of pregnancy, parity and patient's age and were consequently compared with 90 women divided into three similar control groups. The effect of the epidural analgesia was satisfactory in all cases in the three experimental groups, and no complications or side-effects were observed. The advantages of the use of epidural analgesia were the diminished psychological reaction to the abortion, the possibility to perform surgical procedures without any additional anesthesia and the reduction in the duration of the abortion or labor. These advantages justified in our opinion the use of the procedure.", "contents": "Epidural analgesia in midtrimester abortion. Epidural analgesia was performed in 78 women with abortion in the midtrimester or pre-term delivery of up to 27 weeks of pregnancy. The patients were divided into three groups. The first group included thirty women with signs of inevitable abortion. The second group comprised of 9 cases of induced abortion and the third one of 39 cases of pre-term delivery. The three groups were statistically evaluated in relation to time of abortion or labor, fetal weight, weeks of pregnancy, parity and patient's age and were consequently compared with 90 women divided into three similar control groups. The effect of the epidural analgesia was satisfactory in all cases in the three experimental groups, and no complications or side-effects were observed. The advantages of the use of epidural analgesia were the diminished psychological reaction to the abortion, the possibility to perform surgical procedures without any additional anesthesia and the reduction in the duration of the abortion or labor. These advantages justified in our opinion the use of the procedure."}
{"id": "PMID:13015", "title": "The effect of treatment with a low-dose progestagen (Lynestrenol) on hormonal cytology.", "content": "The effect of continuous, low-dose progestagen therapy on endogenous oestrogen production and ovulation in women, was investigated in terms of vaginal cytology. The phase contrast method was used to establish the karyopknotic index from 482 smears from patients using lynestrenol 0.5 mg for oral contraception. The results are presented as the mean of karyopyknotic indices, with standard deviation and standard error of the mean, scored over each three day period of the menstrual cycle, and, in the case of delayed menstruation, over longer periods throughout the protracted cycle. Graphically, the results are shown as average levels compared to controls. Our results show that in patients who have used the preparation for a maximum of three months, cyclic oestrogen production varies only slightly, the mean being within the lower limit of normal and suggesting FSH suppression. In patients who use the preparation for longer periods, the karyopyknotic index becomes similar throughout the cycle to that of controls, being clearly biphasic and generally suggestive of ovulation. In the first group, delayed menstruation seems to be caused mainly by transient FSH suppression. When it occurs in the group treated over a longer period, the disorder appears to be caused by a normo- or hyperoestrogenic, anovulatory condition, due initially to LH suppression with FSH supression setting in later, if the disorder persists longer.", "contents": "The effect of treatment with a low-dose progestagen (Lynestrenol) on hormonal cytology. The effect of continuous, low-dose progestagen therapy on endogenous oestrogen production and ovulation in women, was investigated in terms of vaginal cytology. The phase contrast method was used to establish the karyopknotic index from 482 smears from patients using lynestrenol 0.5 mg for oral contraception. The results are presented as the mean of karyopyknotic indices, with standard deviation and standard error of the mean, scored over each three day period of the menstrual cycle, and, in the case of delayed menstruation, over longer periods throughout the protracted cycle. Graphically, the results are shown as average levels compared to controls. Our results show that in patients who have used the preparation for a maximum of three months, cyclic oestrogen production varies only slightly, the mean being within the lower limit of normal and suggesting FSH suppression. In patients who use the preparation for longer periods, the karyopyknotic index becomes similar throughout the cycle to that of controls, being clearly biphasic and generally suggestive of ovulation. In the first group, delayed menstruation seems to be caused mainly by transient FSH suppression. When it occurs in the group treated over a longer period, the disorder appears to be caused by a normo- or hyperoestrogenic, anovulatory condition, due initially to LH suppression with FSH supression setting in later, if the disorder persists longer."}
{"id": "PMID:13016", "title": "Tubal pregnancy and tubal patency.", "content": "The laparoscopic demonstration of a patent tube usually excludes the present of a tubal pregnancy. In the reported case tubal pregnancy was suspected. Tubal patency was tested because of equivocal laparoscopic findings, and an unexpected tubal pregnancy was diagnosed in the presence of tubal patency.", "contents": "Tubal pregnancy and tubal patency. The laparoscopic demonstration of a patent tube usually excludes the present of a tubal pregnancy. In the reported case tubal pregnancy was suspected. Tubal patency was tested because of equivocal laparoscopic findings, and an unexpected tubal pregnancy was diagnosed in the presence of tubal patency."}
{"id": "PMID:13017", "title": "Ritodrine hydrochloride induced cardiopulmonary and placental hemodynamic changes in normal and hypertensive late pregnancy.", "content": "Cardiopulmonary parameters (minute volume, heart rate, stroke volume, right heart, pulmonary and left heart blood volumes), blood pressure and placental blood flow were evaluated in 20 normal patients, nine patients with preeclamptic disease and 12 with essential hypertension in late pregnancy before and 60 minutes after a single i.m. dose of 10 mg of ritodrine hydrochloride. The drug caused a statistically significant increase in heart rate in all the patient groups, while the systolic and diastolic blood pressures were only slightly affected. Minute volume was unchanged in the group of normal patients, but in both hypertensive groups there was a significant increase. The placental perfusion index was statistically nearly significantly decreased in the group of uncomplicated pregnancies, statistically significantly increased in preeclamptic patients, and not affected in the group with essential hypertension. Ritodrine hydrochloride medication can be expected to have a positive effect on placental blood flow only in preeclamptic disease, and then probably in the milder forms of the disease.", "contents": "Ritodrine hydrochloride induced cardiopulmonary and placental hemodynamic changes in normal and hypertensive late pregnancy. Cardiopulmonary parameters (minute volume, heart rate, stroke volume, right heart, pulmonary and left heart blood volumes), blood pressure and placental blood flow were evaluated in 20 normal patients, nine patients with preeclamptic disease and 12 with essential hypertension in late pregnancy before and 60 minutes after a single i.m. dose of 10 mg of ritodrine hydrochloride. The drug caused a statistically significant increase in heart rate in all the patient groups, while the systolic and diastolic blood pressures were only slightly affected. Minute volume was unchanged in the group of normal patients, but in both hypertensive groups there was a significant increase. The placental perfusion index was statistically nearly significantly decreased in the group of uncomplicated pregnancies, statistically significantly increased in preeclamptic patients, and not affected in the group with essential hypertension. Ritodrine hydrochloride medication can be expected to have a positive effect on placental blood flow only in preeclamptic disease, and then probably in the milder forms of the disease."}
{"id": "PMID:13018", "title": "Carcinoma-in-situ of the cerivix treated with colposcopy guided epithelial conization. Report of a 4-7 year follow-up study.", "content": "Twenty-five patients with the diagnosis of carcinoma-in-situ (CIS) of the cervix were treated with colposcopy guided epithelial conization. During the follow-up study of 4-7 years' duration, there was no recurrence of CIS in 20 of the 25 patients. Between 6 and 12 months after conization, 3 patients showed recurrence of CIS. Two of these patients were treated with further epithelial conization with no evidence of further recurrence 4 years after the second treatment. The third  patient refused to accept further epithelial conization and modified radical hysterectomy was done without any evidence of residual tumour in the hysterectomy specimen. One patient showed stromal invasion in both colposcopically guided biopsy and bone biopsy. Modified radical hysterectomy specimen showed remnants of stromal invasion. One patient with Class IV smear failed to show any atypical transformation zone and cervicitis was proven on colposcopy guided biopsy following treatment with Flagyl. For two of the 25 patients, cytology was Class II and therefore failed to diagnose the pre-malignant condition; but colposcopy showed a grade 3 atypical transformation zone and the presence of CIS was confirmed histologically. Simultaneous use of cytology, colposcopy and colposcopically guided biopsy confirmed the diagnosis of CIS in all cases. The authors recommend colposcopically guided epithelial conization in younger patients, provided the malignant lesion is strictly intra-epithelial, and limited to the ectocervix. Routine follow-up with the aid of cyto-colposcopy remains the key factor in this schedule of therapy.", "contents": "Carcinoma-in-situ of the cerivix treated with colposcopy guided epithelial conization. Report of a 4-7 year follow-up study. Twenty-five patients with the diagnosis of carcinoma-in-situ (CIS) of the cervix were treated with colposcopy guided epithelial conization. During the follow-up study of 4-7 years' duration, there was no recurrence of CIS in 20 of the 25 patients. Between 6 and 12 months after conization, 3 patients showed recurrence of CIS. Two of these patients were treated with further epithelial conization with no evidence of further recurrence 4 years after the second treatment. The third  patient refused to accept further epithelial conization and modified radical hysterectomy was done without any evidence of residual tumour in the hysterectomy specimen. One patient showed stromal invasion in both colposcopically guided biopsy and bone biopsy. Modified radical hysterectomy specimen showed remnants of stromal invasion. One patient with Class IV smear failed to show any atypical transformation zone and cervicitis was proven on colposcopy guided biopsy following treatment with Flagyl. For two of the 25 patients, cytology was Class II and therefore failed to diagnose the pre-malignant condition; but colposcopy showed a grade 3 atypical transformation zone and the presence of CIS was confirmed histologically. Simultaneous use of cytology, colposcopy and colposcopically guided biopsy confirmed the diagnosis of CIS in all cases. The authors recommend colposcopically guided epithelial conization in younger patients, provided the malignant lesion is strictly intra-epithelial, and limited to the ectocervix. Routine follow-up with the aid of cyto-colposcopy remains the key factor in this schedule of therapy."}
{"id": "PMID:13019", "title": "Detection of tumor-specific antigens in human mucinous cystadenocarcinoma of the ovary by immunodiffusion.", "content": "Rabbit antiserum to a tissue extract of human mucinous cystadenocarcinoma of the ovary reacted with tissue extracts of normal ovary and various ovarian malignancies, and ascitic or cystic fluids of ovarian origin by Ouchterlony double gel diffusion and precipitin inhibition techniques. The tumor-associated antigen(s) of mucinous cystadenocarcinoma, which were demonstrated by Ouchterlony double diffusion, were not present in tissue extract of pooled normal ovaries and cystic fluid of benigh tubo-ovarian cyst. An organ-associated tumor antigen as well as the type-specific tumor antigen may exist in mucinous cystadenocarcinoma of the ovary. The mucinous cystadenocarcinoma was not very immunologically different but was distinguishable from serous cystadenocarcinoma and other types of ovarian cancer by double gel diffusion. Precipitin-inhibition reactions demonstated that the adsorbed antiserum to human ovarian mucinous cystadenocarcinoma mixed with tissue extracts of dysgerminoma and serous cystadenocarcinoma, and ascitic fluid of papillary embryonal adenocarcinoma of the ovary could not eliminate the specific precipin line developed with tissue extract of mucinous cystadenocarcinoma.", "contents": "Detection of tumor-specific antigens in human mucinous cystadenocarcinoma of the ovary by immunodiffusion. Rabbit antiserum to a tissue extract of human mucinous cystadenocarcinoma of the ovary reacted with tissue extracts of normal ovary and various ovarian malignancies, and ascitic or cystic fluids of ovarian origin by Ouchterlony double gel diffusion and precipitin inhibition techniques. The tumor-associated antigen(s) of mucinous cystadenocarcinoma, which were demonstrated by Ouchterlony double diffusion, were not present in tissue extract of pooled normal ovaries and cystic fluid of benigh tubo-ovarian cyst. An organ-associated tumor antigen as well as the type-specific tumor antigen may exist in mucinous cystadenocarcinoma of the ovary. The mucinous cystadenocarcinoma was not very immunologically different but was distinguishable from serous cystadenocarcinoma and other types of ovarian cancer by double gel diffusion. Precipitin-inhibition reactions demonstated that the adsorbed antiserum to human ovarian mucinous cystadenocarcinoma mixed with tissue extracts of dysgerminoma and serous cystadenocarcinoma, and ascitic fluid of papillary embryonal adenocarcinoma of the ovary could not eliminate the specific precipin line developed with tissue extract of mucinous cystadenocarcinoma."}
{"id": "PMID:13020", "title": "Fetal heart rate monitoring in cases of decreased fetal movement.", "content": "Thirty pregnant women in the third trimester of pregnancy in whom fetal movements were reduced up to cessation, for at least 12 hours, were monitored for FHR. The FHR 12-48 hours after the cessation of fetal movements was pathological in 21 cases and normal in 9 cases. The most frequent pathological FHR changes were loss of beat to beat variation and variable decelerations. In the following 48 hours another four cases showed pathological FHR changes. One to four days before the reduced fetal movements only six out  of 15 cases showed pathological FHR changes which were L.B.B.V. Meconium was found in only 50% of the cases. It is suggested that pregnant women, especially high risk cases, should record fetal movements as a screening method. FHR monitoring is also a valuable method for detecting antenatal fetal distress, and should be used as an adjunct to fetal movements recording. When acute fetal distress has been established by MAS alone or with FHR change, the fetus should be promptly delivered.", "contents": "Fetal heart rate monitoring in cases of decreased fetal movement. Thirty pregnant women in the third trimester of pregnancy in whom fetal movements were reduced up to cessation, for at least 12 hours, were monitored for FHR. The FHR 12-48 hours after the cessation of fetal movements was pathological in 21 cases and normal in 9 cases. The most frequent pathological FHR changes were loss of beat to beat variation and variable decelerations. In the following 48 hours another four cases showed pathological FHR changes. One to four days before the reduced fetal movements only six out  of 15 cases showed pathological FHR changes which were L.B.B.V. Meconium was found in only 50% of the cases. It is suggested that pregnant women, especially high risk cases, should record fetal movements as a screening method. FHR monitoring is also a valuable method for detecting antenatal fetal distress, and should be used as an adjunct to fetal movements recording. When acute fetal distress has been established by MAS alone or with FHR change, the fetus should be promptly delivered."}
{"id": "PMID:13025", "title": "Effects of intravenous calcitonin on water, electrolyte, and calcium movement across in vivo rabbit jejunum and ileum.", "content": "The influence of intravenously administered synthetic salmon calcitonin on water, electrolyte and calcium fluxes in in vivo rabbit jejunum and ileum was examined. Rabbits were divided into four groups: those receiving (1) saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) calcitonin intravenously while the same intestinal perfusate was used as in group 1; (3) intravenous saline while 10 mM glucose-isotonic saline solution perfused jejunum and ileum; and (4) intravenous calcitonin while the intestinal perfusate was of the same composition as in group 3. Calcitonin provoked a significant increase in jejunal and ileal water, sodium, and bicarbonate secretion in both the glucose-free and glucose-containing perfusate groups. No influence on calcium movement was noted. These results, similar to findings of Gray et al. (J Clin Invest 52:3084-3088, 1975) in human jejunum, suggest that calcitonin may play a role in the pathogenesis of the watery diarrhea noted in about one-third of patients with medullary carcinoma of the thyroid. In addition, these studies demonstrate the usefulness of the rabbit as an animal model with which to investigate further the effects of calcitonin upon intestinal fluid and electrolyte transport.", "contents": "Effects of intravenous calcitonin on water, electrolyte, and calcium movement across in vivo rabbit jejunum and ileum. The influence of intravenously administered synthetic salmon calcitonin on water, electrolyte and calcium fluxes in in vivo rabbit jejunum and ileum was examined. Rabbits were divided into four groups: those receiving (1) saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) calcitonin intravenously while the same intestinal perfusate was used as in group 1; (3) intravenous saline while 10 mM glucose-isotonic saline solution perfused jejunum and ileum; and (4) intravenous calcitonin while the intestinal perfusate was of the same composition as in group 3. Calcitonin provoked a significant increase in jejunal and ileal water, sodium, and bicarbonate secretion in both the glucose-free and glucose-containing perfusate groups. No influence on calcium movement was noted. These results, similar to findings of Gray et al. (J Clin Invest 52:3084-3088, 1975) in human jejunum, suggest that calcitonin may play a role in the pathogenesis of the watery diarrhea noted in about one-third of patients with medullary carcinoma of the thyroid. In addition, these studies demonstrate the usefulness of the rabbit as an animal model with which to investigate further the effects of calcitonin upon intestinal fluid and electrolyte transport."}
{"id": "PMID:13027", "title": "Terminal deoxynucleotidyl transferase as a biological marker for human leukemia.", "content": "High levels of terminal deoxynucleotidyl transferase have been observed in leukocytes of 7 out of 20 patients with chronic myelogenous leukemia in acute blast phase of the disease. These levels are comparable to the levels observed in human and calf thymus gland and cell lines with some T cell characteristics (Molt 4 and 8402). Negligible levels of this activity were observed in chronic myelogenous leukemia not in an acute blast phase of the disease, chronic lymphocytic leukemia, human B cells, mature T cells, and the mixed population of lymphocytes present in normal human blood. The detection of this enzyme in some patients with chronic myelogenous leukemia in acute blast phase of the disease suggests that the blast proliferation may involve primitive stem cells which have more lymphoid than myelogenous characteristics. This enzyme assay may be of use as a biological marker for following patients during treatment and in remission.", "contents": "Terminal deoxynucleotidyl transferase as a biological marker for human leukemia. High levels of terminal deoxynucleotidyl transferase have been observed in leukocytes of 7 out of 20 patients with chronic myelogenous leukemia in acute blast phase of the disease. These levels are comparable to the levels observed in human and calf thymus gland and cell lines with some T cell characteristics (Molt 4 and 8402). Negligible levels of this activity were observed in chronic myelogenous leukemia not in an acute blast phase of the disease, chronic lymphocytic leukemia, human B cells, mature T cells, and the mixed population of lymphocytes present in normal human blood. The detection of this enzyme in some patients with chronic myelogenous leukemia in acute blast phase of the disease suggests that the blast proliferation may involve primitive stem cells which have more lymphoid than myelogenous characteristics. This enzyme assay may be of use as a biological marker for following patients during treatment and in remission."}
{"id": "PMID:13028", "title": "[Pressor action of propranolol; with special reference to relationship between the pressor action and peripheral vascular tone].", "content": "We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone.", "contents": "[Pressor action of propranolol; with special reference to relationship between the pressor action and peripheral vascular tone]. We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone."}
{"id": "PMID:13029", "title": "[Effects of a benzodiazepine derivative, MS4101, on emotional behaviour of untamed cats].", "content": "Effects of MS4101 on emotional behaviour in untamed cats were studied and compared with those of diazepam. Offensive behaviour, i.e., whine response to a rod presented in front of the snout and blowing air on back hair was markedly observed, and whine, attacking and biting responses to tapping with a rod on the back in these cats were marked. Defensive behaviour, i.e., hissing, crouching body, ear flattening to blowing air on back hair, a rod presented and tapping was markedly observed. From 30 min after MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p., offensive behaviour in untamed cats was depressed. ID50 (50% of inhibition dose) of offensive behaviour for MS4101 and diazepam was 2.40 (1.95 approximately 2.95) mg/kg i.p. and 0.96 (0.69 approximately 1.34) mg/kg i.p., respectively. MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p. decreased the offensive behaviour. ID50 of defensive behaviour for MS4101 and diazepam was 3.00 (2.46 approximately 3.66) mg/kg i.p. and 1.45 (1.14 approximately 1.84) mg/kg i.p., respectively. Both MS4101 and diazepam exhibited muscle relaxant effects. Here, diazepam was more effective than MS4101. ED50 of muscle relaxant activity for MS4101 and diazepam was 4.30 (3.03 approximately 6.11) mg/kg i.p., 7.40 (5.04 approximately 10.66) mg/kg i.p., respectively. A single administration of MS4101 and of diazepam in doses 2 mg/kg i.p. enhanced food intake.", "contents": "[Effects of a benzodiazepine derivative, MS4101, on emotional behaviour of untamed cats]. Effects of MS4101 on emotional behaviour in untamed cats were studied and compared with those of diazepam. Offensive behaviour, i.e., whine response to a rod presented in front of the snout and blowing air on back hair was markedly observed, and whine, attacking and biting responses to tapping with a rod on the back in these cats were marked. Defensive behaviour, i.e., hissing, crouching body, ear flattening to blowing air on back hair, a rod presented and tapping was markedly observed. From 30 min after MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p., offensive behaviour in untamed cats was depressed. ID50 (50% of inhibition dose) of offensive behaviour for MS4101 and diazepam was 2.40 (1.95 approximately 2.95) mg/kg i.p. and 0.96 (0.69 approximately 1.34) mg/kg i.p., respectively. MS4101 and diazepam in doses of 2 approximately 4 mg/kg i.p. decreased the offensive behaviour. ID50 of defensive behaviour for MS4101 and diazepam was 3.00 (2.46 approximately 3.66) mg/kg i.p. and 1.45 (1.14 approximately 1.84) mg/kg i.p., respectively. Both MS4101 and diazepam exhibited muscle relaxant effects. Here, diazepam was more effective than MS4101. ED50 of muscle relaxant activity for MS4101 and diazepam was 4.30 (3.03 approximately 6.11) mg/kg i.p., 7.40 (5.04 approximately 10.66) mg/kg i.p., respectively. A single administration of MS4101 and of diazepam in doses 2 mg/kg i.p. enhanced food intake."}
{"id": "PMID:13030", "title": "[The radiological diagnosis of shock lung (author's transl)].", "content": "So-called \"shock lung\" has typical pathological findings; radiologically it is characterised at first by interstitial, late by alveolar pulmonary oedema. This has been shown by a number of case reports. In addition to shock, however, certain intoxications and all forms of left heart failure produce the radiological changes of pulmonary oedema. Transient hyperhydration of the lungs following infusion therapy causes signs of pulmonary oedema which disappear as soon as the fluid balance becomes normal. The radiographic findings of pulmonary oedema correlate well with the intensity and extent of the pathological changes. The radiologist is therefore in a position to evaluate the severity of the shock lung; this is a valuable addition to the clinical findings and the results of physiological tests and blood gas analysis. It has to be emphasised that the radiological changes appear at an early stage, in any case much sooner than the clinical features. Radiological findings may be present without abnormalities on oscultation or percussion. Radiographs of the lungs are therefore indicated in all patients who may be subject to shock lung, particularly if they suffer from undiagnosed hyperventilation.", "contents": "[The radiological diagnosis of shock lung (author's transl)]. So-called \"shock lung\" has typical pathological findings; radiologically it is characterised at first by interstitial, late by alveolar pulmonary oedema. This has been shown by a number of case reports. In addition to shock, however, certain intoxications and all forms of left heart failure produce the radiological changes of pulmonary oedema. Transient hyperhydration of the lungs following infusion therapy causes signs of pulmonary oedema which disappear as soon as the fluid balance becomes normal. The radiographic findings of pulmonary oedema correlate well with the intensity and extent of the pathological changes. The radiologist is therefore in a position to evaluate the severity of the shock lung; this is a valuable addition to the clinical findings and the results of physiological tests and blood gas analysis. It has to be emphasised that the radiological changes appear at an early stage, in any case much sooner than the clinical features. Radiological findings may be present without abnormalities on oscultation or percussion. Radiographs of the lungs are therefore indicated in all patients who may be subject to shock lung, particularly if they suffer from undiagnosed hyperventilation."}
{"id": "PMID:13031", "title": "[The spina bifida child with special reference to urologic disease].", "content": "From the view of the urological diseases a new conception of the spina bifida cystica is represented. The first part contains informations on etiology, pathological anatomy and physio-pathology. Considering the urological diseases (neurogenic bladder with incontinence and residual urine, vesico ureteric reflux and chronic pyelonephritis) special importance is attached to the pathogenesis. Within the therapeutic methods the treatment with the alpha-blocking agent Phenoxybenzamin (Dibenzyran, R\u00f6hm Pharma GmbH, Darmstadt) is emphasized as the actual therapy of the neurogenic bladder. The operative indication of the Ileum-Conduit (Bricker-) is mentioned. An analysis of 125 spina bifida-patients with the pathological findings in the kidneys and the urinary tract is given.", "contents": "[The spina bifida child with special reference to urologic disease]. From the view of the urological diseases a new conception of the spina bifida cystica is represented. The first part contains informations on etiology, pathological anatomy and physio-pathology. Considering the urological diseases (neurogenic bladder with incontinence and residual urine, vesico ureteric reflux and chronic pyelonephritis) special importance is attached to the pathogenesis. Within the therapeutic methods the treatment with the alpha-blocking agent Phenoxybenzamin (Dibenzyran, R\u00f6hm Pharma GmbH, Darmstadt) is emphasized as the actual therapy of the neurogenic bladder. The operative indication of the Ileum-Conduit (Bricker-) is mentioned. An analysis of 125 spina bifida-patients with the pathological findings in the kidneys and the urinary tract is given."}
{"id": "PMID:13032", "title": "[The development of vaccination as demonstrated on the development of the Bavarian State Vaccination Institute in the 19th and 20th centuries].", "content": "In 1801 the smallpox vaccination has been introduced in Bavaria by order of the Duke Franz Joseph. He appointed a Medical Superintendent, responsible for smallpox vaccinations for the whole country. This was the hour of birth for the Institute, too. The Institute developed quickly to a point of crystallization in the field of prophylactic medicine, research on infectious diseases and social pediatrics. By this Institute the \"Retrovaccine\" against smallpox was introduced 1856. 1967 -- 1976 an attenuated life smallpox-vaccine (MVA) has been developed. Some years ago the activities of the Institute had been focussed into research of complications after vaccinations and up to date, on the pathogenesis of Multiple Sclerosis. A historical review demonstrates the development of the Institute in the past up to modern activities in research, teaching students and postgraduate education and in medical practice.", "contents": "[The development of vaccination as demonstrated on the development of the Bavarian State Vaccination Institute in the 19th and 20th centuries]. In 1801 the smallpox vaccination has been introduced in Bavaria by order of the Duke Franz Joseph. He appointed a Medical Superintendent, responsible for smallpox vaccinations for the whole country. This was the hour of birth for the Institute, too. The Institute developed quickly to a point of crystallization in the field of prophylactic medicine, research on infectious diseases and social pediatrics. By this Institute the \"Retrovaccine\" against smallpox was introduced 1856. 1967 -- 1976 an attenuated life smallpox-vaccine (MVA) has been developed. Some years ago the activities of the Institute had been focussed into research of complications after vaccinations and up to date, on the pathogenesis of Multiple Sclerosis. A historical review demonstrates the development of the Institute in the past up to modern activities in research, teaching students and postgraduate education and in medical practice."}
{"id": "PMID:13033", "title": "[Smallpox vaccine, then and now. From the \"cow lymphe\" to the cell-culture vaccine].", "content": "There have been few changes in the preparation of smallpox vaccine since Eduard Jenner described his method of preventive inoculation in 1798. Jenner's vaccine, \"the matter\", was maintained in man by arm to arm passage. The only major achievement in production methods was the introduction of an animal host for virus propagation. The skin of living calves or sheep was inoculated with seed virus and the \"pulp\" harvested three to four days later. The disadvantages of this procedure are evident: massive bacterial contamination in spite of rigorous cleanliness and excessive amounts of undesired tissue debris in the crude material to be used for vaccine production. In spite of these obvious disadvantages the method is still in use all over the world. Advances in tissue culture techniques have led to the production of all modern vaccines for use in animals and in the human from this substrate with low initial content of foreign protein and of primary sterility. The only exception today is conventional smallpox vaccine. Sporadic attempts to produce smallpox vaccine in tissue culture have been recently and successfully made in England, Holland and Yugoslavia. The Bavarian State Institute of Vaccination has adopted Vaccinia strain Elstree to primary cultures of chick embryo fibroblasts. The virus propagation in roller bottles permits the economical production of a high titered vaccine with a stability equal to that of calf origin. The cell culture harvest is bacteriologically steril and has a minimal content of foreign protein. Within the past two years this cell culture vaccine has totally replaced the old \"calf lymph\". Vaccination takes are equal, complications have so far not come to our attention.", "contents": "[Smallpox vaccine, then and now. From the \"cow lymphe\" to the cell-culture vaccine]. There have been few changes in the preparation of smallpox vaccine since Eduard Jenner described his method of preventive inoculation in 1798. Jenner's vaccine, \"the matter\", was maintained in man by arm to arm passage. The only major achievement in production methods was the introduction of an animal host for virus propagation. The skin of living calves or sheep was inoculated with seed virus and the \"pulp\" harvested three to four days later. The disadvantages of this procedure are evident: massive bacterial contamination in spite of rigorous cleanliness and excessive amounts of undesired tissue debris in the crude material to be used for vaccine production. In spite of these obvious disadvantages the method is still in use all over the world. Advances in tissue culture techniques have led to the production of all modern vaccines for use in animals and in the human from this substrate with low initial content of foreign protein and of primary sterility. The only exception today is conventional smallpox vaccine. Sporadic attempts to produce smallpox vaccine in tissue culture have been recently and successfully made in England, Holland and Yugoslavia. The Bavarian State Institute of Vaccination has adopted Vaccinia strain Elstree to primary cultures of chick embryo fibroblasts. The virus propagation in roller bottles permits the economical production of a high titered vaccine with a stability equal to that of calf origin. The cell culture harvest is bacteriologically steril and has a minimal content of foreign protein. Within the past two years this cell culture vaccine has totally replaced the old \"calf lymph\". Vaccination takes are equal, complications have so far not come to our attention."}
{"id": "PMID:13038", "title": "Role of urinary solutes in natural immunity to gonorrhea.", "content": "Natural resistance of the male urethra to gonococci has not been explained by classical immune mechanisms but could result from antibacterial properties of urine. Accordingly, we measured survival in midmorning urine of 10(7) F-62 T2 gonococci per ml by serial dilutions and plate counts. Fifteen killer urines from eight people all killed greater than 3 logs (average, 5.3), and 13 of 15 were sterilized. Fourteen nonkiller (inhibitor) urines from seven subjects allowed no growth. Killer urines were more acidic (pH 5.4 versus 6.4) and more concentrated (861 versus 717 mosmol/kg) than nonkillers. Upon addition of hydrogen ion, urea, and sodium chloride to urines and broth, pH proved to be the major killing factor, but urea and NaCl were also bactericidal. Susceptibility to urine bactericidal power did not vary with colony type (T2 versus T4) or strain (F-62 versus two fresh isolates). Killing was rapid (0.5 to 3 h) and not bacteriolytic. Escherichia coli multiplied 10-fold in urines that inhibited growth of gonococci. Thus, the bacteriostatic effect of urine may explain why gonococci do not infect the bladder and kidney during gonorrhea. The bactericidal properties of urine may contribute to resistance against gonococcal urethritis.", "contents": "Role of urinary solutes in natural immunity to gonorrhea. Natural resistance of the male urethra to gonococci has not been explained by classical immune mechanisms but could result from antibacterial properties of urine. Accordingly, we measured survival in midmorning urine of 10(7) F-62 T2 gonococci per ml by serial dilutions and plate counts. Fifteen killer urines from eight people all killed greater than 3 logs (average, 5.3), and 13 of 15 were sterilized. Fourteen nonkiller (inhibitor) urines from seven subjects allowed no growth. Killer urines were more acidic (pH 5.4 versus 6.4) and more concentrated (861 versus 717 mosmol/kg) than nonkillers. Upon addition of hydrogen ion, urea, and sodium chloride to urines and broth, pH proved to be the major killing factor, but urea and NaCl were also bactericidal. Susceptibility to urine bactericidal power did not vary with colony type (T2 versus T4) or strain (F-62 versus two fresh isolates). Killing was rapid (0.5 to 3 h) and not bacteriolytic. Escherichia coli multiplied 10-fold in urines that inhibited growth of gonococci. Thus, the bacteriostatic effect of urine may explain why gonococci do not infect the bladder and kidney during gonorrhea. The bactericidal properties of urine may contribute to resistance against gonococcal urethritis."}
{"id": "PMID:13039", "title": "Effects of pneumococcal mucopeptide and capsular polysaccharide on phagocytosis.", "content": "Pneumoccal cell wall and capsular products from eight serotypes were tested for their ability to inhibit polymorphonuclear neutrophil killing of the same eight pneumococcal strains. Crude pneumococcal cell wall preparations from all serotypes inhibited phagocytic killing of several pneumococcal serotypes, and were just as effective with heterologous as with homologous strains. Phagocytosis dependent on heat-labile serum factors was inhibited, whereas phagocytosis not dependent on heat-labile factors was not significantly affected. These findings were compatible with inhibition of complement consumption. The inhibitory activity was found in a purified cell wall mucopeptide, whereas purified capsular polysaccharides failed to inhibit phagocytosis.", "contents": "Effects of pneumococcal mucopeptide and capsular polysaccharide on phagocytosis. Pneumoccal cell wall and capsular products from eight serotypes were tested for their ability to inhibit polymorphonuclear neutrophil killing of the same eight pneumococcal strains. Crude pneumococcal cell wall preparations from all serotypes inhibited phagocytic killing of several pneumococcal serotypes, and were just as effective with heterologous as with homologous strains. Phagocytosis dependent on heat-labile serum factors was inhibited, whereas phagocytosis not dependent on heat-labile factors was not significantly affected. These findings were compatible with inhibition of complement consumption. The inhibitory activity was found in a purified cell wall mucopeptide, whereas purified capsular polysaccharides failed to inhibit phagocytosis."}
{"id": "PMID:13040", "title": "Glucosyltransferase production by Streptococcus sanguis 804 (NCTC 10904).", "content": "Streptococcus sanguis 804 (NCTC 10904) was grown ih batch culture at constant pH. and the glucosyltransferase activity of the supernatant was assayed over a 40-h growth period. The optimum pH for enzyme production was 7.0 to 7.2. During growth of the culture, three reproducible phases of enzyme activity were observed. The polysaccharides synthesized during each of these phases were characterized as dextran-like glucans by analysis of acid hydrolysates, gas-liquid chromatography, and a specific aggregation technique. The glucans were studied further by infrared spectroscopy, enzymic degradation, and periodate oxidation. Differences in the proportions of alpha-(1 leads to 3)- and alpha-(1 leads to 6)-linkages were observed. The results suggest that glucan synthesis by S. sanguis involves a multienzyme system.", "contents": "Glucosyltransferase production by Streptococcus sanguis 804 (NCTC 10904). Streptococcus sanguis 804 (NCTC 10904) was grown ih batch culture at constant pH. and the glucosyltransferase activity of the supernatant was assayed over a 40-h growth period. The optimum pH for enzyme production was 7.0 to 7.2. During growth of the culture, three reproducible phases of enzyme activity were observed. The polysaccharides synthesized during each of these phases were characterized as dextran-like glucans by analysis of acid hydrolysates, gas-liquid chromatography, and a specific aggregation technique. The glucans were studied further by infrared spectroscopy, enzymic degradation, and periodate oxidation. Differences in the proportions of alpha-(1 leads to 3)- and alpha-(1 leads to 6)-linkages were observed. The results suggest that glucan synthesis by S. sanguis involves a multienzyme system."}
{"id": "PMID:13041", "title": "Production and detection of staphylococcal elastase.", "content": "The optimum conditions were determined for the production and detection of staphylococcal elastase from Staphylococcus epidermidis. Optimum production and recovery took place when the dialysis membrane technique was utilized with brain heart infusion agar incubated for 44 h under 15% CO2 and harvested in physiological saline. Near-optimal production took place by 28 h, and this was found more useful for routine use. Incorporation of elastin into the culture medium or the inoculum did not result in higher levels of elastase production. The detection system consisted of 0.25% particulate elastin suspended in a pH 7.0, 0.05 M tris(hydroxymethyl)aminomethane-hydrochloride-buffered solidified plated medium. Crude undialyzed elastase was best detected when the medium contained either agarose and 10(-3) M calcium or purified agar without additional additives. Crude dialyzed elastase was best detected when the medium contained agarose and 10(-3) M disodium ethylenediaminetetraacetic acid.", "contents": "Production and detection of staphylococcal elastase. The optimum conditions were determined for the production and detection of staphylococcal elastase from Staphylococcus epidermidis. Optimum production and recovery took place when the dialysis membrane technique was utilized with brain heart infusion agar incubated for 44 h under 15% CO2 and harvested in physiological saline. Near-optimal production took place by 28 h, and this was found more useful for routine use. Incorporation of elastin into the culture medium or the inoculum did not result in higher levels of elastase production. The detection system consisted of 0.25% particulate elastin suspended in a pH 7.0, 0.05 M tris(hydroxymethyl)aminomethane-hydrochloride-buffered solidified plated medium. Crude undialyzed elastase was best detected when the medium contained either agarose and 10(-3) M calcium or purified agar without additional additives. Crude dialyzed elastase was best detected when the medium contained agarose and 10(-3) M disodium ethylenediaminetetraacetic acid."}
{"id": "PMID:13047", "title": "Side effects on fetus and infant of psychotropic drug use during pregnancy.", "content": "Psychotropic drugs are used frequently for the treatment of emotional as well as other disorders. With usage so widespread, many pregnant women receive psychotropic drugs. Maternal ingestion of these drugs may produce, in the fetus, side effects including withdrawal symptoms. Withdrawal signs in the fetus as a result of maternal intake of opiates, hypnotics, analgesics, and tricyclic antidepressant drugs have been reported. Fetal side effects can occur by maternal ingestion of nuroleptic medications, lithium, antidepressants, anxiolytic sedatives, anticonvulsants, and bromides. The author feels that even though these drugs are generally safe, they must only be administered to pregnant women when absolutely needed, and then under vigilance.", "contents": "Side effects on fetus and infant of psychotropic drug use during pregnancy. Psychotropic drugs are used frequently for the treatment of emotional as well as other disorders. With usage so widespread, many pregnant women receive psychotropic drugs. Maternal ingestion of these drugs may produce, in the fetus, side effects including withdrawal symptoms. Withdrawal signs in the fetus as a result of maternal intake of opiates, hypnotics, analgesics, and tricyclic antidepressant drugs have been reported. Fetal side effects can occur by maternal ingestion of nuroleptic medications, lithium, antidepressants, anxiolytic sedatives, anticonvulsants, and bromides. The author feels that even though these drugs are generally safe, they must only be administered to pregnant women when absolutely needed, and then under vigilance."}
{"id": "PMID:13048", "title": "Stability of mammalian lens phosphofructokinase.", "content": "Two interconvertible phosphofructokinase (PFK) forms were found in rat and human lenses; whereas only one predominant form was found in calf lens. PFK isolated from these lenses possessed a common property, i.e., pH-dependent cold (or acid) lability. The inactivation was prevented by including either adenosine triphosphate (ATP) or fructose-6-phosphate (fru-6-P) in the incubating media. The protective effect of ATP or fru-6-P was complete in rat or calf lenses. In human lens, although fru-6-P was fully protective, ATP protected only partially. The inactivation could be reversed by addition of fru-6-P, but not ATP, to the incubating media at 37.5 degrees C. Lens organ culture studies showed that the depletion of lenticular ATP seemed to precipitate the loss of PFK.", "contents": "Stability of mammalian lens phosphofructokinase. Two interconvertible phosphofructokinase (PFK) forms were found in rat and human lenses; whereas only one predominant form was found in calf lens. PFK isolated from these lenses possessed a common property, i.e., pH-dependent cold (or acid) lability. The inactivation was prevented by including either adenosine triphosphate (ATP) or fructose-6-phosphate (fru-6-P) in the incubating media. The protective effect of ATP or fru-6-P was complete in rat or calf lenses. In human lens, although fru-6-P was fully protective, ATP protected only partially. The inactivation could be reversed by addition of fru-6-P, but not ATP, to the incubating media at 37.5 degrees C. Lens organ culture studies showed that the depletion of lenticular ATP seemed to precipitate the loss of PFK."}
{"id": "PMID:13049", "title": "Methenamine and its salts as urinary tract antiseptics: variables affecting the antibacterial activity of formaldehyde, mandelic acid, and hippuric acid in vitro.", "content": "The activities of formaldehyde and of mandelic and hippuric acids, alone and in combination, have been tested against some 300 strains of bacteria typical of those causing urinary tract infections. In a chemically defined medium, which resembles urine in many respects, formaldehyde had a mean minimal inhibitory concentration of 13 mug per ml. Activity was several fold lower in media (nutrient agar and tryptic soy agar) that contained significant amounts of protein. The activity of formaldehyde is virtually unaffected by pH in the range of 5 to 8. Mandelic and hippuric acids (2 mg per ml) have limited antimicrobial activity at acid pH values only. The combination of formaldehyde with mandelic acid (2 mg per ml) was additive, most markedly at pH 5; the formaldehyde-hippuric acid combination, however, did not appear to be additive. Our findings suggest that, at pH values between 5 and 6, an antibacterial concentration of formaldehyde will be generated from methenamine within approximately 1 hr after being excreted into the urine.", "contents": "Methenamine and its salts as urinary tract antiseptics: variables affecting the antibacterial activity of formaldehyde, mandelic acid, and hippuric acid in vitro. The activities of formaldehyde and of mandelic and hippuric acids, alone and in combination, have been tested against some 300 strains of bacteria typical of those causing urinary tract infections. In a chemically defined medium, which resembles urine in many respects, formaldehyde had a mean minimal inhibitory concentration of 13 mug per ml. Activity was several fold lower in media (nutrient agar and tryptic soy agar) that contained significant amounts of protein. The activity of formaldehyde is virtually unaffected by pH in the range of 5 to 8. Mandelic and hippuric acids (2 mg per ml) have limited antimicrobial activity at acid pH values only. The combination of formaldehyde with mandelic acid (2 mg per ml) was additive, most markedly at pH 5; the formaldehyde-hippuric acid combination, however, did not appear to be additive. Our findings suggest that, at pH values between 5 and 6, an antibacterial concentration of formaldehyde will be generated from methenamine within approximately 1 hr after being excreted into the urine."}
{"id": "PMID:13050", "title": "Interaction of uricine with uric acid and its effect on uric acid precipitation.", "content": "Uricine is a yellow-red pigment isolated from uric acid stones where it is always found. It binds to the uric acid, as shown by gel chromatography, at constant uric acid elution. It also increases the capacity of the uric acid to form larger aggregates and therefore the capacity of the uric acid to precipitate is enhanced. The uric acid-uricine aggregates may be separated by high speed sucrose centrifugation gradients.", "contents": "Interaction of uricine with uric acid and its effect on uric acid precipitation. Uricine is a yellow-red pigment isolated from uric acid stones where it is always found. It binds to the uric acid, as shown by gel chromatography, at constant uric acid elution. It also increases the capacity of the uric acid to form larger aggregates and therefore the capacity of the uric acid to precipitate is enhanced. The uric acid-uricine aggregates may be separated by high speed sucrose centrifugation gradients."}
{"id": "PMID:13054", "title": "Adenosine triphosphate catabolism in homogenates of rat secretory enamel organs incubated in histochemical lead media.", "content": "To investigate how lead, when used as trapping agent, influences the ATP hydrolysis and to study how ATP is catalyzed in histochemical systems, homogenized secretory enamel organs were incubated in histochemical [3H]-ATP media. Aliquots from the media were taken after 3, 10, 20 and 30 min, the ATP and formed metabolites were separated by electrophoresis and radiometrically quantitated. In media lacking both lead and homogenate 2% of the ATP was spontaneously hydrolyzed during 30 min incubation at room temperature. The presence of lead caused an additional 8% hydrolysis at pH 7.2 and an additional 20% hydrolysis at pH 9.4. In the presence of homogenate, however, lead caused a net decrease of the hydrolysis of ATP as well as of ADP and AMP. This enzyme inhibition varied from around zero to some 80%, depending on pH and substrated involved. In homogenate-containing lead media, at both pH 7.2 AND 9.4, ATP was rapidly hydrolyzed primarily to ADP and subsequently to AMP and adenosine and/or inosine. After 5--10 min ADP constituted the predominant substrate at both pH:s. At pH 7.2 ADP remained so for the rest of the incubation, whereas at pH 9.4 AMP was predominant substrate at the end of the incubation. AMP was the finan catabolic product in experiments at pH 7.2, and adenosine and/or inosine at pH 9.4. Inorganic phosphate was liberated almost linearly during the whole incubation period. The results indicate that histochemical studies of substrate specific ATP-ases should be performed with short incubation times and, when high specific activities are present, in large quantities of incubation media to reduce interference by ADP and AMP hydrolyzing enzymes.", "contents": "Adenosine triphosphate catabolism in homogenates of rat secretory enamel organs incubated in histochemical lead media. To investigate how lead, when used as trapping agent, influences the ATP hydrolysis and to study how ATP is catalyzed in histochemical systems, homogenized secretory enamel organs were incubated in histochemical [3H]-ATP media. Aliquots from the media were taken after 3, 10, 20 and 30 min, the ATP and formed metabolites were separated by electrophoresis and radiometrically quantitated. In media lacking both lead and homogenate 2% of the ATP was spontaneously hydrolyzed during 30 min incubation at room temperature. The presence of lead caused an additional 8% hydrolysis at pH 7.2 and an additional 20% hydrolysis at pH 9.4. In the presence of homogenate, however, lead caused a net decrease of the hydrolysis of ATP as well as of ADP and AMP. This enzyme inhibition varied from around zero to some 80%, depending on pH and substrated involved. In homogenate-containing lead media, at both pH 7.2 AND 9.4, ATP was rapidly hydrolyzed primarily to ADP and subsequently to AMP and adenosine and/or inosine. After 5--10 min ADP constituted the predominant substrate at both pH:s. At pH 7.2 ADP remained so for the rest of the incubation, whereas at pH 9.4 AMP was predominant substrate at the end of the incubation. AMP was the finan catabolic product in experiments at pH 7.2, and adenosine and/or inosine at pH 9.4. Inorganic phosphate was liberated almost linearly during the whole incubation period. The results indicate that histochemical studies of substrate specific ATP-ases should be performed with short incubation times and, when high specific activities are present, in large quantities of incubation media to reduce interference by ADP and AMP hydrolyzing enzymes."}
{"id": "PMID:13055", "title": "Immunotherapy in two foals with combined immunodeficiency, resulting in graft versus host reaction.", "content": "Immunotherapy was attempted in 2 Arabian foals with combined immunodeficiency. One foal was given a transplant of bone marrow from a selected full sibling, and 1 foal was given a fetal thymus transplant. Both foals died. Genetic evidence was obtained for survival of the transplanted tissues in both cases; however, a graft versus host reaction developed in the foal given the fetal thymus transplant.", "contents": "Immunotherapy in two foals with combined immunodeficiency, resulting in graft versus host reaction. Immunotherapy was attempted in 2 Arabian foals with combined immunodeficiency. One foal was given a transplant of bone marrow from a selected full sibling, and 1 foal was given a fetal thymus transplant. Both foals died. Genetic evidence was obtained for survival of the transplanted tissues in both cases; however, a graft versus host reaction developed in the foal given the fetal thymus transplant."}
{"id": "PMID:13053", "title": "Treatment of chronic ventricular arrhythmias [proceedings].", "content": "Treatment of ventricular arrhythmias at the present time is difficult and requires a strong commitment on the part of the physician and the patient. Adequate documentation of the arrhythmia with continuous ECG recordings (Holter recordings), preferably for 24 hours, should be performed in each case. Exercise testing can be utilized in selected patients, but is generally inferior to the Holter technique. Underlying cardiac pathology should be searched for, utilizing echocardiography in all patients and coronary angiography and left ventriculography in patients with more severe ventricular tachycardias. Estimation of the prognostic significance of the VPBs must be made in the context of the underlying disease, and goals for treatment must be set. Treatment in all cases first requires measures to avoid known precipitating factors. If antiarrhythmic therapy is utilized, a systematic empirical trial of available agents should be undertaken, utilizing repeated Holter monitoring to document effectiveness. Serum levels of the antiarrhythmic medications should be measured in most cases. Combinations of antiarrhythmic agents can be employed if the need is great, but the agents singly are ineffective. If treatment is determined to be ineffective, it should be discontinued. Surgical techniques may be useful in cases of refractory ventricular tachycardia, and they include overdrive pacing, surgical sympathectomy, or ventricular aneurysmectomy with or without coronary bypass. Coronary bypass alone or resection of a hypokinetic but not aneurysmal area of myocardium may be successful in some cases, but the results are less predictable than when a true aneurysm is resected. Electrophysiologic studies, performed as part of the preoperative evaluation and provoking a self-perpetuating ventricular tachycardia, may permit selection of patients suitable for ventriculotomy to interrupt the re-entry pathway. At present, this must be considered experimental and is performed in only a few centers equipped for the required complex epicardial mapping. Surgery has not been shown to affect complex VPBs outside the setting of acute ischemia. Control of ventricular arrhythmias requires a highly individualistic approach with documentation of effectiveness.", "contents": "Treatment of chronic ventricular arrhythmias [proceedings]. Treatment of ventricular arrhythmias at the present time is difficult and requires a strong commitment on the part of the physician and the patient. Adequate documentation of the arrhythmia with continuous ECG recordings (Holter recordings), preferably for 24 hours, should be performed in each case. Exercise testing can be utilized in selected patients, but is generally inferior to the Holter technique. Underlying cardiac pathology should be searched for, utilizing echocardiography in all patients and coronary angiography and left ventriculography in patients with more severe ventricular tachycardias. Estimation of the prognostic significance of the VPBs must be made in the context of the underlying disease, and goals for treatment must be set. Treatment in all cases first requires measures to avoid known precipitating factors. If antiarrhythmic therapy is utilized, a systematic empirical trial of available agents should be undertaken, utilizing repeated Holter monitoring to document effectiveness. Serum levels of the antiarrhythmic medications should be measured in most cases. Combinations of antiarrhythmic agents can be employed if the need is great, but the agents singly are ineffective. If treatment is determined to be ineffective, it should be discontinued. Surgical techniques may be useful in cases of refractory ventricular tachycardia, and they include overdrive pacing, surgical sympathectomy, or ventricular aneurysmectomy with or without coronary bypass. Coronary bypass alone or resection of a hypokinetic but not aneurysmal area of myocardium may be successful in some cases, but the results are less predictable than when a true aneurysm is resected. Electrophysiologic studies, performed as part of the preoperative evaluation and provoking a self-perpetuating ventricular tachycardia, may permit selection of patients suitable for ventriculotomy to interrupt the re-entry pathway. At present, this must be considered experimental and is performed in only a few centers equipped for the required complex epicardial mapping. Surgery has not been shown to affect complex VPBs outside the setting of acute ischemia. Control of ventricular arrhythmias requires a highly individualistic approach with documentation of effectiveness."}
{"id": "PMID:13056", "title": "Microbial acetylation of M factor of virginiamycin.", "content": "The M component of virginiamycin was found to be modified by whole cells or cell-free enzyme preparations of a Staphylococcus aureus strain. It was shown that this reaction proceeds by enzymatic acetylation of the secondary alcoholic function of the molecule, followed by a rapid chemical degradation of the O-acetylated product.", "contents": "Microbial acetylation of M factor of virginiamycin. The M component of virginiamycin was found to be modified by whole cells or cell-free enzyme preparations of a Staphylococcus aureus strain. It was shown that this reaction proceeds by enzymatic acetylation of the secondary alcoholic function of the molecule, followed by a rapid chemical degradation of the O-acetylated product."}
{"id": "PMID:13058", "title": "Rapid, shallow breathing after Ascaris suum antigen inhalation: role of vagus nerves.", "content": "In five treadmill-exercising, unsedated dogs, we studied the effect of inhaled Ascaris suum antigen aerosols on minute volume of ventilation (VE), respiratory frequency (f), tidal volume (VT), total pulmonary resistance (RL), and dynamic pulmonary compliance (CLdyn), before and during cooling of the vagus nerves. With the vagi warm, inhaled antigen increased VE (mean + 62%; P less than 0.01)by increasing f (mean + 180%; P less than 0.01), despite a decrease in VT (mean - 42%; P less than 0.01). RL increased (mean + 170%; P less than 0.001) and CLdyn decreased (mean - 43%; P less than 0.005). With the vagi cool, inhaled antigen no longer affected VE, f, or VT (P greater than 0.5), although RL still increased and CLdyn still decreased. Inhalation of a bronchodilator, terbutaline, prevented the broncho-constriction induced by antigen but did not prevent the ventilatory response. We conclude that vagal afferent pathways mediate the ventilatory response to inhaled antigen and suggest that the primary stimulus for this response is not airway narrowing.", "contents": "Rapid, shallow breathing after Ascaris suum antigen inhalation: role of vagus nerves. In five treadmill-exercising, unsedated dogs, we studied the effect of inhaled Ascaris suum antigen aerosols on minute volume of ventilation (VE), respiratory frequency (f), tidal volume (VT), total pulmonary resistance (RL), and dynamic pulmonary compliance (CLdyn), before and during cooling of the vagus nerves. With the vagi warm, inhaled antigen increased VE (mean + 62%; P less than 0.01)by increasing f (mean + 180%; P less than 0.01), despite a decrease in VT (mean - 42%; P less than 0.01). RL increased (mean + 170%; P less than 0.001) and CLdyn decreased (mean - 43%; P less than 0.005). With the vagi cool, inhaled antigen no longer affected VE, f, or VT (P greater than 0.5), although RL still increased and CLdyn still decreased. Inhalation of a bronchodilator, terbutaline, prevented the broncho-constriction induced by antigen but did not prevent the ventilatory response. We conclude that vagal afferent pathways mediate the ventilatory response to inhaled antigen and suggest that the primary stimulus for this response is not airway narrowing."}
{"id": "PMID:13059", "title": "pH effects on lactate and excess lactate in relation to O2 deficit in hypoxic dogs.", "content": "Both hypoxemia and alkalemia increase arterial lactate levels, but excess lactate (XL) may be better related to the true O2 deficit and less subject to the pH effect upon glycolysis. To test this idea, 50 anesthetized (30 ml/kg pentobarbital sodium) and paralyzed dogs in five groups were ventilated with low O2 mixtures. Arterial pH was altered by CO2, hyperventilation, and HCO3- so that the average pH of the five groups were 6.99, 7.21, 7.34, 7.53, and 7.54 (+ propranolol). Pyruvate and lactate levels rose at rates roughly corresponding to pH. In all animals, rise of lactate (deltaL), XL and net O2 deficit were linear with time and the slope accurately described the rate of rise. When the ratio of XL rate deltaL rate was plotted against pH, it increased toward unity as pH decreased to 6.9. The ratio of deltaL rate to true O2 deficit rate also showed a significant pH effect by increasing with pH. Ratio of XL rate to true O2 deficit rate, on the other hand, was independent of pH. XL may correct for red cell lactate production which is not affected by O2 supply but is influenced by pH.", "contents": "pH effects on lactate and excess lactate in relation to O2 deficit in hypoxic dogs. Both hypoxemia and alkalemia increase arterial lactate levels, but excess lactate (XL) may be better related to the true O2 deficit and less subject to the pH effect upon glycolysis. To test this idea, 50 anesthetized (30 ml/kg pentobarbital sodium) and paralyzed dogs in five groups were ventilated with low O2 mixtures. Arterial pH was altered by CO2, hyperventilation, and HCO3- so that the average pH of the five groups were 6.99, 7.21, 7.34, 7.53, and 7.54 (+ propranolol). Pyruvate and lactate levels rose at rates roughly corresponding to pH. In all animals, rise of lactate (deltaL), XL and net O2 deficit were linear with time and the slope accurately described the rate of rise. When the ratio of XL rate deltaL rate was plotted against pH, it increased toward unity as pH decreased to 6.9. The ratio of deltaL rate to true O2 deficit rate also showed a significant pH effect by increasing with pH. Ratio of XL rate to true O2 deficit rate, on the other hand, was independent of pH. XL may correct for red cell lactate production which is not affected by O2 supply but is influenced by pH."}
{"id": "PMID:13061", "title": "Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A.", "content": "Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.", "contents": "Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides."}
{"id": "PMID:13062", "title": "Human adenosine deaminase. Purification and subunit structure.", "content": "Human erythrocyte adenosine deaminase has been purified approximately 800,000-fold to apparent homogeneity using antibody affinity chromatography. The enzyme was shown to be a single polypeptide chain with an estimated molecular weight of approximately 38,000. The three electrophoretic forms of erythrocyte adenosine deaminase purified simultaneously by this technique were indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Several properties of the highly purified adenosine deaminase including pH optimum, Km for substrate, Ki for product, Stokes radius, sedimentation coefficient, and apparent substrate specificity were identical with the properties observed with an impure preparation of the enzyme.", "contents": "Human adenosine deaminase. Purification and subunit structure. Human erythrocyte adenosine deaminase has been purified approximately 800,000-fold to apparent homogeneity using antibody affinity chromatography. The enzyme was shown to be a single polypeptide chain with an estimated molecular weight of approximately 38,000. The three electrophoretic forms of erythrocyte adenosine deaminase purified simultaneously by this technique were indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Several properties of the highly purified adenosine deaminase including pH optimum, Km for substrate, Ki for product, Stokes radius, sedimentation coefficient, and apparent substrate specificity were identical with the properties observed with an impure preparation of the enzyme."}
{"id": "PMID:13063", "title": "The carbon monoxide-binding hemoprotein reducible by hydrogen peroxide in microsomal fractions of pea seeds.", "content": "There exist at least two kinds of CO-binding hemoproteins in microsomal fractions of germinating pea (Pisum sativum) seeds. One of them is cytochrome P-450 and the other is also a protoheme protein (judged from its pyridine hemochrome spectrum), which is not hitherto reported. The content of the new hemoprotein is much higher than that of cytochrome P-450 in the early stage of germination. During germination the former decreases and the latter increases. The new hemoprotein is not appreciably reduced by sodium dithionite alone within a few minutes, but, it is easily reduced by dithionite in the presence of methyl viologen and also by hydrogen peroxide when CO is present. The addition of hydrogen peroxide to pea microsomes in the absence of CO causes destruction of the hemoprotein and also decolorization of endogenous carotenoid. Destruction of these components is brought about by organic hydroperoxides independently of the presence of CO. In the presence of hydroxylamine, the addition of hydroperoxides to the microsomes results in the formation of an absorption spectrum similar to the spectra of ferrous-NO complexes of protoheme proteins. When N,N-dimethyl p-phenylenediamine is present, the reaction of pea microsomes with hydroperoxides gives a spectrum similar to that of the ferryl form of myoglobin. The reactions of the hemoprotein with hydroperoxides are inhibited by alpha,alpha'-dipyridyl and aniline, with which pea microsomes form binding spectra. The microsomes form a rather stable difference spectrum with hydroxylamine. However, the hemoprotein is destroyed when hydroxylamine is added to the microsomes in the reduced state.", "contents": "The carbon monoxide-binding hemoprotein reducible by hydrogen peroxide in microsomal fractions of pea seeds. There exist at least two kinds of CO-binding hemoproteins in microsomal fractions of germinating pea (Pisum sativum) seeds. One of them is cytochrome P-450 and the other is also a protoheme protein (judged from its pyridine hemochrome spectrum), which is not hitherto reported. The content of the new hemoprotein is much higher than that of cytochrome P-450 in the early stage of germination. During germination the former decreases and the latter increases. The new hemoprotein is not appreciably reduced by sodium dithionite alone within a few minutes, but, it is easily reduced by dithionite in the presence of methyl viologen and also by hydrogen peroxide when CO is present. The addition of hydrogen peroxide to pea microsomes in the absence of CO causes destruction of the hemoprotein and also decolorization of endogenous carotenoid. Destruction of these components is brought about by organic hydroperoxides independently of the presence of CO. In the presence of hydroxylamine, the addition of hydroperoxides to the microsomes results in the formation of an absorption spectrum similar to the spectra of ferrous-NO complexes of protoheme proteins. When N,N-dimethyl p-phenylenediamine is present, the reaction of pea microsomes with hydroperoxides gives a spectrum similar to that of the ferryl form of myoglobin. The reactions of the hemoprotein with hydroperoxides are inhibited by alpha,alpha'-dipyridyl and aniline, with which pea microsomes form binding spectra. The microsomes form a rather stable difference spectrum with hydroxylamine. However, the hemoprotein is destroyed when hydroxylamine is added to the microsomes in the reduced state."}
{"id": "PMID:13064", "title": "Purification and properties of 3-keto-5-aminohexanoate cleavage enzyme from a lysine-fermenting Clostridium.", "content": "The lysine-fermenting Clostridium SB4 is shown to contain a new type of beta-keto acid-degrading enzyme that converts 3-keto-5-aminohexanoate and acetyl-CoA reversibly to L-3-aminobutyryl-CoA and acetoacetate. Following the development of a sensitive radiochemical assay the enzyme was purified 175-fold to about 90% homogeneity in 44% yield. The specific activity of the purified enzyme is 44 IU/mg of protein at 30 degrees. The equilibrium constant for the forward reaction was found to be 0.68 at 30 degrees and pH 7.0, corresponding to a deltaG0' of 0.23 kcal/mol. The enzyme is highly substrate-specific. Of several substrate analogs tested in the forward and back reactions only beta-alanyl-CoA and D-3-aminobutyryl-CoA are utilized about 130% and 1.7% as fast as L-3-aminobutyryl-CoA, respectively. The product formed from beta-alanyl-CoA and acetoacetate is a neutral beta-keto acid, presumably 3-keto-5-aminopentanoic acid; its borohydride reduction product was partially characterized as a hydroxy-amino acid by various chromatographic and ion exchange methods. The activity of the purified enzyme is increased about 5-fold by addition of 0.1 mM Co2+ and to a lesser extent by Mn2+. Activity is inhibited by orthophosphate, thiol reagents, and EDTA; however, exposure of the enzyme to the latter compound prior to addition of Co2+ increases activity, presumably by removing competing divalent cations. Tracer experiments have shown that carbon atoms 1 and 2 of acetoacetate are derived from carbon atoms 1 and 2 of 3-keto-5-aminohexanoate whereas carbon atoms 3 and 4 are derived from acetyl-CoA. The amino acid moiety of 3-aminobutyryl-CoA is derived from carbon atoms 3 to 6 of 3-keto-5-aminohexanoate. Since no evidence for covalent enzyme-substrate intermediates could be obtained by the study of four possible group exchange reactions, a concerted reaction between 3-keto-5-aminohexanoate and acetyl-CoA is considered. The enzyme has a molecular weight of about 97,000 and probably contains four identical subunits. The relatively high specific activity of the enzyme in extracts of Clostridium SB4 indicates it functions in the main pathway of lysine degradation. This relatively stable enzyme provides a convenient and specific method for the quantitative estimation of nanomolar amounts of L- and D-3-aminobutyryl-CoA and beta-alanyl-CoA.", "contents": "Purification and properties of 3-keto-5-aminohexanoate cleavage enzyme from a lysine-fermenting Clostridium. The lysine-fermenting Clostridium SB4 is shown to contain a new type of beta-keto acid-degrading enzyme that converts 3-keto-5-aminohexanoate and acetyl-CoA reversibly to L-3-aminobutyryl-CoA and acetoacetate. Following the development of a sensitive radiochemical assay the enzyme was purified 175-fold to about 90% homogeneity in 44% yield. The specific activity of the purified enzyme is 44 IU/mg of protein at 30 degrees. The equilibrium constant for the forward reaction was found to be 0.68 at 30 degrees and pH 7.0, corresponding to a deltaG0' of 0.23 kcal/mol. The enzyme is highly substrate-specific. Of several substrate analogs tested in the forward and back reactions only beta-alanyl-CoA and D-3-aminobutyryl-CoA are utilized about 130% and 1.7% as fast as L-3-aminobutyryl-CoA, respectively. The product formed from beta-alanyl-CoA and acetoacetate is a neutral beta-keto acid, presumably 3-keto-5-aminopentanoic acid; its borohydride reduction product was partially characterized as a hydroxy-amino acid by various chromatographic and ion exchange methods. The activity of the purified enzyme is increased about 5-fold by addition of 0.1 mM Co2+ and to a lesser extent by Mn2+. Activity is inhibited by orthophosphate, thiol reagents, and EDTA; however, exposure of the enzyme to the latter compound prior to addition of Co2+ increases activity, presumably by removing competing divalent cations. Tracer experiments have shown that carbon atoms 1 and 2 of acetoacetate are derived from carbon atoms 1 and 2 of 3-keto-5-aminohexanoate whereas carbon atoms 3 and 4 are derived from acetyl-CoA. The amino acid moiety of 3-aminobutyryl-CoA is derived from carbon atoms 3 to 6 of 3-keto-5-aminohexanoate. Since no evidence for covalent enzyme-substrate intermediates could be obtained by the study of four possible group exchange reactions, a concerted reaction between 3-keto-5-aminohexanoate and acetyl-CoA is considered. The enzyme has a molecular weight of about 97,000 and probably contains four identical subunits. The relatively high specific activity of the enzyme in extracts of Clostridium SB4 indicates it functions in the main pathway of lysine degradation. This relatively stable enzyme provides a convenient and specific method for the quantitative estimation of nanomolar amounts of L- and D-3-aminobutyryl-CoA and beta-alanyl-CoA."}
{"id": "PMID:13065", "title": "Mannosyltransferase activity in calf pancreas microsomes. Formation of 14C-labeled lipid-linked oligosaccharides from GDP-D-[14C]mannose and pancreatic dolichyl beta-D-[14C]mannopyranosyl phosphate.", "content": "Calf pancreas microsomes incorporated radioactive D-mannose from GDP-D-[14C]mannose into lipid-bound oligosaccharides extracted with chloroform/methanol/water (10/10/2.5, v/v). Several products, which probably differed in the size of the oligosaccharide moiety, were labeled. These could be partially resolved by thin layer chromatography and DEAE-cellulose chromatography. The labeled lipid-bound oligosaccharides were retained on DEAE-cellulose more strongly than synthetic dolichyl alpha-D-[14C]mannopyranosyl phosphate. They were stable to mild alkali, but labile to acid and hot alkali. Acid treatment yielded a neutral 14C-labeled oligosaccharide fraction which was estimated by gel filtration to have a minimum of 8 monosaccharide residues. Hot alkali treatment yielded a mixture of neutral and acidic 14C-labeled oligosaccharides which could be transformed into neutral products by alkaline phosphatase. The D-[14C]mannose residues were alpha-linked at the nonreducing terminus of the oligosaccharides since they could be removed completely with alpha-mannosidase. Most of the D-[14C]mannose-labeled oligosaccharides were retained on concanavalin A Sepharose and eluted with methyl alpha-D-mannopyranoside. Pancreatic dolichyl beta-D-[14C]mannopyranosyl phosphate incubated with calf pancreas microsomes in the presence of sodium taurocholate was efficiently utilized as donor of alpha-D-mannosyl residues in lipid-bound oligosaccharides. The products formed from dolichyl beta-D-[14C]mannopyranosyl phosphate were identical with those formed from GDP-D-[14C]mannose, and evidence was obtained to show that the dolichyl beta-D-[14C]mannopyranosyl phosphate was serving as donor without prior conversion to GDP-D-[14C]mannose. Transfer of mannose from dolichyl beta-D-[14C]mannopyranosyl phosphate to lipid-bound oligosaccharides took place at a pH optimum of 7.3, whereas transfer to the precipitate containing glycoproteins was greatest at pH 6.0 in Tris/maleate buffer. The addition of divalent cation was not required, but low concentrations of EDTA were extremely inhibitory. The carbohydrate composition of the lipid-bound oligosaccharides of microsomal membranes was investigated by gas-liquid chromatography and by reduction with sodium borotritide. A heterogeneous mixture of oligosaccharides containing N-acetyl-D-glucosamine, D-mannose, and D-glucose varying in proportions from approximately 1/2.5/0.5 to 1/5/1.5 was obtained with glucosamine at the reducing end. Acid treatment of the lipid-bound oligosaccharide fraction yielded dolichyl pyrophosphate, suggesting that at least some of the oligosaccharides were linked to dolichol through a pyrophosphate group.", "contents": "Mannosyltransferase activity in calf pancreas microsomes. Formation of 14C-labeled lipid-linked oligosaccharides from GDP-D-[14C]mannose and pancreatic dolichyl beta-D-[14C]mannopyranosyl phosphate. Calf pancreas microsomes incorporated radioactive D-mannose from GDP-D-[14C]mannose into lipid-bound oligosaccharides extracted with chloroform/methanol/water (10/10/2.5, v/v). Several products, which probably differed in the size of the oligosaccharide moiety, were labeled. These could be partially resolved by thin layer chromatography and DEAE-cellulose chromatography. The labeled lipid-bound oligosaccharides were retained on DEAE-cellulose more strongly than synthetic dolichyl alpha-D-[14C]mannopyranosyl phosphate. They were stable to mild alkali, but labile to acid and hot alkali. Acid treatment yielded a neutral 14C-labeled oligosaccharide fraction which was estimated by gel filtration to have a minimum of 8 monosaccharide residues. Hot alkali treatment yielded a mixture of neutral and acidic 14C-labeled oligosaccharides which could be transformed into neutral products by alkaline phosphatase. The D-[14C]mannose residues were alpha-linked at the nonreducing terminus of the oligosaccharides since they could be removed completely with alpha-mannosidase. Most of the D-[14C]mannose-labeled oligosaccharides were retained on concanavalin A Sepharose and eluted with methyl alpha-D-mannopyranoside. Pancreatic dolichyl beta-D-[14C]mannopyranosyl phosphate incubated with calf pancreas microsomes in the presence of sodium taurocholate was efficiently utilized as donor of alpha-D-mannosyl residues in lipid-bound oligosaccharides. The products formed from dolichyl beta-D-[14C]mannopyranosyl phosphate were identical with those formed from GDP-D-[14C]mannose, and evidence was obtained to show that the dolichyl beta-D-[14C]mannopyranosyl phosphate was serving as donor without prior conversion to GDP-D-[14C]mannose. Transfer of mannose from dolichyl beta-D-[14C]mannopyranosyl phosphate to lipid-bound oligosaccharides took place at a pH optimum of 7.3, whereas transfer to the precipitate containing glycoproteins was greatest at pH 6.0 in Tris/maleate buffer. The addition of divalent cation was not required, but low concentrations of EDTA were extremely inhibitory. The carbohydrate composition of the lipid-bound oligosaccharides of microsomal membranes was investigated by gas-liquid chromatography and by reduction with sodium borotritide. A heterogeneous mixture of oligosaccharides containing N-acetyl-D-glucosamine, D-mannose, and D-glucose varying in proportions from approximately 1/2.5/0.5 to 1/5/1.5 was obtained with glucosamine at the reducing end. Acid treatment of the lipid-bound oligosaccharide fraction yielded dolichyl pyrophosphate, suggesting that at least some of the oligosaccharides were linked to dolichol through a pyrophosphate group."}
{"id": "PMID:13066", "title": "Collagen cross-linking. Effect of D-penicillamine on cross-linking in vitro.", "content": "D-Pencillamine is believed to inhibit collagen cross-link biosynthesis by forming thiazolidine rings with lysyl-derived aldehydes that are intermediates in bifunctional cross-link synthesis. Recently, we showed that aldehyde biosynthesis catalyzed by lysyl oxidase occurs after the onset of fibril formation and that nascent aldehydes form Schiff-base cross-links rapidly in fibrils. This suggested that the accessibility of D-penicillamine to most aldehydes formed during cross-link synthesis might be limited. To study this, reconstituted chick bone collagen fibrils were incubated in vitro with highly purified lysyl oxidase and D-penicillamine. As reported in previous studies in vivo, allysine content increased and polyfunctional cross-link synthesis decreased with D-penicillamine. However, the concentration of bifunctional cross-links increased rather than decreased due to a 2-fold increase in N6:6'-dehydro-5,5'-dihydroxylysinonorleucine. Hydroxyallysine, an intermediate in formation of this Schiff base, decreased. A time study indicated that allysine levels increased primarily after the bulk of Schiff base synthesis. These results indicate that D-penicillamine does not inhibit bifunctional cross-link synthesis as previously suggested. Its principal effect is to block synthesis of polyfunctional cross-link products from Schiff base cross-link precursors and to cause accumulation of these precursors. This effect may be due to interference with the close molecular packing required for polyfunctional cross-link synthesis. These results also suggest a mechanism for the relative insensitivity of tissues such as bone with high hydroxylysine content to D-penicillamine. In this study, D-penicillamine caused selective accumulation of allysyl and not hydroxyallysyl residues. In bone as opposed to soft tissues, hydroxyallysyl residues are intermediates in synthesis of almost all cross-links.", "contents": "Collagen cross-linking. Effect of D-penicillamine on cross-linking in vitro. D-Pencillamine is believed to inhibit collagen cross-link biosynthesis by forming thiazolidine rings with lysyl-derived aldehydes that are intermediates in bifunctional cross-link synthesis. Recently, we showed that aldehyde biosynthesis catalyzed by lysyl oxidase occurs after the onset of fibril formation and that nascent aldehydes form Schiff-base cross-links rapidly in fibrils. This suggested that the accessibility of D-penicillamine to most aldehydes formed during cross-link synthesis might be limited. To study this, reconstituted chick bone collagen fibrils were incubated in vitro with highly purified lysyl oxidase and D-penicillamine. As reported in previous studies in vivo, allysine content increased and polyfunctional cross-link synthesis decreased with D-penicillamine. However, the concentration of bifunctional cross-links increased rather than decreased due to a 2-fold increase in N6:6'-dehydro-5,5'-dihydroxylysinonorleucine. Hydroxyallysine, an intermediate in formation of this Schiff base, decreased. A time study indicated that allysine levels increased primarily after the bulk of Schiff base synthesis. These results indicate that D-penicillamine does not inhibit bifunctional cross-link synthesis as previously suggested. Its principal effect is to block synthesis of polyfunctional cross-link products from Schiff base cross-link precursors and to cause accumulation of these precursors. This effect may be due to interference with the close molecular packing required for polyfunctional cross-link synthesis. These results also suggest a mechanism for the relative insensitivity of tissues such as bone with high hydroxylysine content to D-penicillamine. In this study, D-penicillamine caused selective accumulation of allysyl and not hydroxyallysyl residues. In bone as opposed to soft tissues, hydroxyallysyl residues are intermediates in synthesis of almost all cross-links."}
{"id": "PMID:13067", "title": "Lectin purification on affinity columns containing reductively aminated disaccharides.", "content": "A method is described for isolating lectins in pure form and quantitative yield in a single step by affinity chromatography on aminoethyl polyacrylamide gels containing reductively aminated disaccharide residues. The affinity columns were prepared in two steps: (a) direct reductive amination of the disaccharide and aminoethyl gel with sodium cyanoborohydride in aqueous solution at pH 9; (b) N-acetylation of excess amino groups. Affinity columns prepared by reductive amination of lactose, melibiose, maltose, and di-N-acetylchitobiose were used to purify the following lectins: lactose, peanut, castor bean; melibiose, Bandeiraea simplicifolia; maltose, jack bean, common lentil; di-N-acetylchitobiose, wheat germ. These columns are extremely stable, have good flow rates, and high binding capacities.", "contents": "Lectin purification on affinity columns containing reductively aminated disaccharides. A method is described for isolating lectins in pure form and quantitative yield in a single step by affinity chromatography on aminoethyl polyacrylamide gels containing reductively aminated disaccharide residues. The affinity columns were prepared in two steps: (a) direct reductive amination of the disaccharide and aminoethyl gel with sodium cyanoborohydride in aqueous solution at pH 9; (b) N-acetylation of excess amino groups. Affinity columns prepared by reductive amination of lactose, melibiose, maltose, and di-N-acetylchitobiose were used to purify the following lectins: lactose, peanut, castor bean; melibiose, Bandeiraea simplicifolia; maltose, jack bean, common lentil; di-N-acetylchitobiose, wheat germ. These columns are extremely stable, have good flow rates, and high binding capacities."}
{"id": "PMID:13068", "title": "pH-dependent conformational states of horse liver alcohol dehydrogenase.", "content": "The quenching of liver alcohol dehydrogenase protein fluorescence at alkaline pH indicates two conformational states of the enzyme with a pKa of 9.8+/-0.2, shifted to 10.6+/-0.2 in D2O. NAD+ and 2-p-toluidinonaphthalene-6-sulfonate, a fluorescent probe competitive with coenzyme, bind to the acid conformation of the enzyme. The pKa of the protein-fluorescence quenching curve is shifted toward 7.6 in the presence of NAD+, and the ternary complex formation with NAD+ and trifluoroethanol results in a pH-independent maximal quench. At pH (pD) 10.5, the rate constant for NAD+ binding was 2.6 times faster in D2O2 than in  H2O due to the shift of the pKa. Based on these results, a scheme has been proposed in which the state of protonation of an enzyme functional group with a pKa of 9.8 controls the conformational state of the enzyme. NAD+ binds to the acid conformation and subsequently causes another conformational change resulting in the perturbation of the pKa to 7.6. Alcohol then binds to the unprotonated form of the functional group with a pKa of 7.6 in the binary enzyme-NAD+ complex and converts the enzyme to the alkaline conformation. Thus, at neutral pH liver alcohol dehydrogenase undergoes two conformational changes en route to the ternary complex in which hydride transfer occurs.", "contents": "pH-dependent conformational states of horse liver alcohol dehydrogenase. The quenching of liver alcohol dehydrogenase protein fluorescence at alkaline pH indicates two conformational states of the enzyme with a pKa of 9.8+/-0.2, shifted to 10.6+/-0.2 in D2O. NAD+ and 2-p-toluidinonaphthalene-6-sulfonate, a fluorescent probe competitive with coenzyme, bind to the acid conformation of the enzyme. The pKa of the protein-fluorescence quenching curve is shifted toward 7.6 in the presence of NAD+, and the ternary complex formation with NAD+ and trifluoroethanol results in a pH-independent maximal quench. At pH (pD) 10.5, the rate constant for NAD+ binding was 2.6 times faster in D2O2 than in  H2O due to the shift of the pKa. Based on these results, a scheme has been proposed in which the state of protonation of an enzyme functional group with a pKa of 9.8 controls the conformational state of the enzyme. NAD+ binds to the acid conformation and subsequently causes another conformational change resulting in the perturbation of the pKa to 7.6. Alcohol then binds to the unprotonated form of the functional group with a pKa of 7.6 in the binary enzyme-NAD+ complex and converts the enzyme to the alkaline conformation. Thus, at neutral pH liver alcohol dehydrogenase undergoes two conformational changes en route to the ternary complex in which hydride transfer occurs."}
{"id": "PMID:13069", "title": "NADPH-cytochrome P-450 reductase. Circular dichroism and physical studies.", "content": "NADPH-cytochrome P-450 reductase was purified from hepatic microsomes of phenobarbital and hydrocortisone-treated rats by detergent solubilization and column chromatography. This membrane protein contains 31 mol per cent hydrophobic amino acid residues, 6 half-cystine residues, and a single tryptophan residue as determined by amino acid analysis after mineral or organic acid hydrolysis. The free mobility of cytochrome P-450 reductase in sodium dodecyl sulfate was identical to that of several soluble proteins used as standards (i.e. ovalbumin, bovin serum albumin, erythrocuprein, beta-galactosidase). Molecular weight estimates from sedimentation equilibrium studies in the presence of guanidine hydrochloride (76,500) are consistent with those determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate at various per cent gel concentrations (79,000 to 80,000). Computer analysis of circular dichroism spectra of cytochrome P-450 reductase in the far ultraviolet region indicated the presence of 34 per cent alpha helical and 16 per cent beta structure. The amount of random structure was calculated to be 50 per cent.", "contents": "NADPH-cytochrome P-450 reductase. Circular dichroism and physical studies. NADPH-cytochrome P-450 reductase was purified from hepatic microsomes of phenobarbital and hydrocortisone-treated rats by detergent solubilization and column chromatography. This membrane protein contains 31 mol per cent hydrophobic amino acid residues, 6 half-cystine residues, and a single tryptophan residue as determined by amino acid analysis after mineral or organic acid hydrolysis. The free mobility of cytochrome P-450 reductase in sodium dodecyl sulfate was identical to that of several soluble proteins used as standards (i.e. ovalbumin, bovin serum albumin, erythrocuprein, beta-galactosidase). Molecular weight estimates from sedimentation equilibrium studies in the presence of guanidine hydrochloride (76,500) are consistent with those determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate at various per cent gel concentrations (79,000 to 80,000). Computer analysis of circular dichroism spectra of cytochrome P-450 reductase in the far ultraviolet region indicated the presence of 34 per cent alpha helical and 16 per cent beta structure. The amount of random structure was calculated to be 50 per cent."}
{"id": "PMID:13070", "title": "Purification and properties of acetyl coenzyme A synthetase from bakers' yeast.", "content": "Acetyl-CoA synthetase, utilized in a coupled reaction system, has been shown to be applicable to the spectrophotometric determination of propionic and methylmalonic acids in biological fluids. The isolation of acetyl-CoA synthetase from yeast is simpler than the purification from mammalian sources. This study also presents some properties of the yeast enzyme and compares it to the more extensively studied enzyme isolated from ammmalian tissue. Isolation and purification yielded a preparation with a specific activity of 44 units/mg at 25 degrees. The purified acetyl-CoA synthetase was apparently homogeneous by sodium dodecyl sulfate-poly-acrylamide gel electrophoresis with an estimated subunit molecular weight of 78,000. Polyacrylamide gel electrophoresis in the presence of ATP revealed a single protein band which contained all of the enzyme activity. Analytical ultra-centrifuge studies indicated the presence of a single protein with a molecular wright of 151,000 and sedimentation velocity analysis revealed a single peak with a sedimentation coefficient of 8.65 So20,w. Similar to the enzyme from mammalian sources, yeast acetyl-CoA synthetase has a high degree of substrate specificity and is active only on acetate and propionate. In addition, the reaction mechanism, as demonstrated by initial velocity patterns obtained from substrate pairs, appeared to be identical to the enzyme from bovine heart. However, the apparent Michaelis constants for the substrates were significantly different from the mammalian enzyme. The yeast-derived enzyme also differed from the mammalian in terms of molecular weight, amino acid composition, pH optimum, effect of monovalent cations, and stability characteristics. Thus, yeast acetyl-CoA synthetase is more easily purified than the mammalian enzyme and provides an excellent preparation for the assay of propionic and methylmalonic acids.", "contents": "Purification and properties of acetyl coenzyme A synthetase from bakers' yeast. Acetyl-CoA synthetase, utilized in a coupled reaction system, has been shown to be applicable to the spectrophotometric determination of propionic and methylmalonic acids in biological fluids. The isolation of acetyl-CoA synthetase from yeast is simpler than the purification from mammalian sources. This study also presents some properties of the yeast enzyme and compares it to the more extensively studied enzyme isolated from ammmalian tissue. Isolation and purification yielded a preparation with a specific activity of 44 units/mg at 25 degrees. The purified acetyl-CoA synthetase was apparently homogeneous by sodium dodecyl sulfate-poly-acrylamide gel electrophoresis with an estimated subunit molecular weight of 78,000. Polyacrylamide gel electrophoresis in the presence of ATP revealed a single protein band which contained all of the enzyme activity. Analytical ultra-centrifuge studies indicated the presence of a single protein with a molecular wright of 151,000 and sedimentation velocity analysis revealed a single peak with a sedimentation coefficient of 8.65 So20,w. Similar to the enzyme from mammalian sources, yeast acetyl-CoA synthetase has a high degree of substrate specificity and is active only on acetate and propionate. In addition, the reaction mechanism, as demonstrated by initial velocity patterns obtained from substrate pairs, appeared to be identical to the enzyme from bovine heart. However, the apparent Michaelis constants for the substrates were significantly different from the mammalian enzyme. The yeast-derived enzyme also differed from the mammalian in terms of molecular weight, amino acid composition, pH optimum, effect of monovalent cations, and stability characteristics. Thus, yeast acetyl-CoA synthetase is more easily purified than the mammalian enzyme and provides an excellent preparation for the assay of propionic and methylmalonic acids."}
{"id": "PMID:13071", "title": "Purification and properties of a heat-stable glucocerebrosidase activating factor from control and Gaucher spleen.", "content": "Gaucher's disease is a lysosomal storage disease caused by a deficiency in the enzyme glucocerebrosidase. A small, heat-stable glycoprotein first obtained from Gaucher spleen (Ho, M. W., and O'Brien, J. S. (1971) Proc. Natl. Acad. Sci. U. S.A. 68, 2810-2813) has been observed to stimulate the activity of glucocerebrosidase isolated from normal tissue. It has been suggested that this material might be important in the physiological catabolism of glucocerebroside in normal individuals (Ho, M. W. (1974) in Enzyme Therapy in Lysosomal Storage Diseases (Tager, J. M., Hooghwinkel, G. J. M., and Daems, W. Th., eds) pp.239-246, North-Holland Publishing Co., Amsterdam). In order to investigate this suggestion, glucocerebrosidase activating factors were isolated and purified from control and Gaucher spleen and characterized. Although approximately the same mass of activator was isolated from both spleens, the two activators differ from one another in a number of important respects: (a) the activator from the control spleen is only 6 per cent as active (on a protein basis) as the activator from Gaucher spleen; (b) the amino acid compositions of the purified activators are significantly different; and (c) carbohydrate analysis of the purified activators indicates that the activator from Gaucher spleen is a glycoprotein, while that from control spleen is not. Comparative kinetic studies demonstrate that the anionic detergent, sodium taurocholate, and the acidic phospholipid, phosphatidylinositol, both stimulate glucocerebrosidase activity to a larger extent than the activator substance from Gaucher spleen. The activator from Gaucher spleen and human liver glucocerebrosidase both appear to contain significant hydrophobic character. We conclude that the activator is probably not physiologically important in the catabolism of glucocerebroside in normal tissues. The significance of the occurrence of this apparently unique glycoprotein activator in Gaucher spleen remains obscure; however, its presence represents another interesting aspect of Gaucher's disease that warrants further investigation.", "contents": "Purification and properties of a heat-stable glucocerebrosidase activating factor from control and Gaucher spleen. Gaucher's disease is a lysosomal storage disease caused by a deficiency in the enzyme glucocerebrosidase. A small, heat-stable glycoprotein first obtained from Gaucher spleen (Ho, M. W., and O'Brien, J. S. (1971) Proc. Natl. Acad. Sci. U. S.A. 68, 2810-2813) has been observed to stimulate the activity of glucocerebrosidase isolated from normal tissue. It has been suggested that this material might be important in the physiological catabolism of glucocerebroside in normal individuals (Ho, M. W. (1974) in Enzyme Therapy in Lysosomal Storage Diseases (Tager, J. M., Hooghwinkel, G. J. M., and Daems, W. Th., eds) pp.239-246, North-Holland Publishing Co., Amsterdam). In order to investigate this suggestion, glucocerebrosidase activating factors were isolated and purified from control and Gaucher spleen and characterized. Although approximately the same mass of activator was isolated from both spleens, the two activators differ from one another in a number of important respects: (a) the activator from the control spleen is only 6 per cent as active (on a protein basis) as the activator from Gaucher spleen; (b) the amino acid compositions of the purified activators are significantly different; and (c) carbohydrate analysis of the purified activators indicates that the activator from Gaucher spleen is a glycoprotein, while that from control spleen is not. Comparative kinetic studies demonstrate that the anionic detergent, sodium taurocholate, and the acidic phospholipid, phosphatidylinositol, both stimulate glucocerebrosidase activity to a larger extent than the activator substance from Gaucher spleen. The activator from Gaucher spleen and human liver glucocerebrosidase both appear to contain significant hydrophobic character. We conclude that the activator is probably not physiologically important in the catabolism of glucocerebroside in normal tissues. The significance of the occurrence of this apparently unique glycoprotein activator in Gaucher spleen remains obscure; however, its presence represents another interesting aspect of Gaucher's disease that warrants further investigation."}
{"id": "PMID:13072", "title": "Multiple low spin forms of the cytochrome c ferrihemochrome. EPR spectra of various eukaryotic and prokaryotic cytochromes c.", "content": "1. Despite the same methionine-sulfur:heme-iron:imidazole-nitrogen hemochrome structure observed by x-ray crystallography in four of the seven c-type eukaryotic and prokaryotic cytochromes examined, and the occurrence of the characteristic  695 nm absorption band correlated with the presence of a methionine-sulfur:heme-iron axial ligand in all seven proteins, they fall into two distinct classes on the basis of their EPR and optical spectra. The horse, tuna, and bakers' yeast iso-1 cytochromes c have a predominant neutral pH EPR form with g1=3.06, g2=2.26, and g3=1.25, while the bakers' yeast iso-2 and Euglena cytochromes c, the Rhodospirillum rubrum cytochrome c2, and the Paracoccus denitrificans cytochrome c550 all have a predominant neutral pH EPR form with g1=3.2, g2=2.05, and g3=1.39. The ferricytochromes with g1=3.06 have a B-Q splitting that is approximately 150 cm-1 larger than the ferricytochromes with g1=3.2. 2. Each of the cytochromes displays up to four low spin EPR forms that are in pH-dependent equilibrium and can all be observed at near neutral pH. As the pH is raised the predominant neutral pH form is converted into two forms with g1=3.4 and g1=3.6, identified by comparsion with model compounds and other heme proteins as epsilon-amino:heme-iron:imidazole and bis-epsilon-amino:heme-iron ferrihemochromes, respectively. 3. The pK for the conversion of the predominant neutral pH EPR form into the alkaline pH forms is the same as the pK for the disappearance of the 695 nm absorption band for the cytochromes, even though these pK values range over 2 pH units. This confirms that the g1=3.06 and g1=3.2 forms contain the methionine-sulfur:heme-iron axial ligand while the g1=3.4 and the g1=3.6 forms do not. 4. At extremes of pH, the horse and bakers' yeast iso-1 proteins display several high and low spin forms that are identified, showing that a variety of protein-derived ligands will coordinate to the heme iron including methionine and cysteine sulfur, histidine imidazole, and lysine epsilon-amine. 5. The spectrum of horse cytochrome c with added azide, cyanide, hydroxide, or imidazole as axial ligands has also been examined. 6. From a comparison of the EPR and optical spectral characteristics of these groups of cytochromes with model compounds, it is suggested that the difference between them is due to a change in the hydrogen bonding or perhaps even in the protonation of N-1 of the heme iron-bound histidine imidazole.", "contents": "Multiple low spin forms of the cytochrome c ferrihemochrome. EPR spectra of various eukaryotic and prokaryotic cytochromes c. 1. Despite the same methionine-sulfur:heme-iron:imidazole-nitrogen hemochrome structure observed by x-ray crystallography in four of the seven c-type eukaryotic and prokaryotic cytochromes examined, and the occurrence of the characteristic  695 nm absorption band correlated with the presence of a methionine-sulfur:heme-iron axial ligand in all seven proteins, they fall into two distinct classes on the basis of their EPR and optical spectra. The horse, tuna, and bakers' yeast iso-1 cytochromes c have a predominant neutral pH EPR form with g1=3.06, g2=2.26, and g3=1.25, while the bakers' yeast iso-2 and Euglena cytochromes c, the Rhodospirillum rubrum cytochrome c2, and the Paracoccus denitrificans cytochrome c550 all have a predominant neutral pH EPR form with g1=3.2, g2=2.05, and g3=1.39. The ferricytochromes with g1=3.06 have a B-Q splitting that is approximately 150 cm-1 larger than the ferricytochromes with g1=3.2. 2. Each of the cytochromes displays up to four low spin EPR forms that are in pH-dependent equilibrium and can all be observed at near neutral pH. As the pH is raised the predominant neutral pH form is converted into two forms with g1=3.4 and g1=3.6, identified by comparsion with model compounds and other heme proteins as epsilon-amino:heme-iron:imidazole and bis-epsilon-amino:heme-iron ferrihemochromes, respectively. 3. The pK for the conversion of the predominant neutral pH EPR form into the alkaline pH forms is the same as the pK for the disappearance of the 695 nm absorption band for the cytochromes, even though these pK values range over 2 pH units. This confirms that the g1=3.06 and g1=3.2 forms contain the methionine-sulfur:heme-iron axial ligand while the g1=3.4 and the g1=3.6 forms do not. 4. At extremes of pH, the horse and bakers' yeast iso-1 proteins display several high and low spin forms that are identified, showing that a variety of protein-derived ligands will coordinate to the heme iron including methionine and cysteine sulfur, histidine imidazole, and lysine epsilon-amine. 5. The spectrum of horse cytochrome c with added azide, cyanide, hydroxide, or imidazole as axial ligands has also been examined. 6. From a comparison of the EPR and optical spectral characteristics of these groups of cytochromes with model compounds, it is suggested that the difference between them is due to a change in the hydrogen bonding or perhaps even in the protonation of N-1 of the heme iron-bound histidine imidazole."}
{"id": "PMID:13073", "title": "Activation of guanylate cyclase in cerebral cortex of rat by hydroxylamine.", "content": "Hydroxylamine actived guanylate cyclase in particulate fraction of cerebral cortex of rat. Activation was most remarkable in crude mitochondrial fraction. When the crude mitochondrial fraction was subjected to osmotic shock and fractionated, guanylate cyclase activity recovered in the subfractions as assayed with hydroxylamine was only one-third of the starting material. Recombination of the soluble and the particulate fractions, however, restored guanylate cyclase activity to the same level as that of the starting material. When varying quantities of the particulate and soluble fractions were combined, enzyme activity was proportional to the quantity of the soluble fraction. Heating of the soluble or particulate fraction at 55 degrees for 5 min inactivated guanylate cyclase. The heated particulate fraction markedly activated guanylate cyclase activity in the native soluble fraction, while the heated soluble fraction did not stimulate enzyme activity in the particulate. The particulate fraction preincubated with hydroxylamine at 37 degrees for 5 min followed by washing activated guanylate cyclase activity in the soluble fraction in the absence of hydroxylamine. Further fractionation of the crude mitochondrial fraction revealed that the factor(s) needed for the activation by hydroxylamine is associated with the mitochondria. The mitochondrial fraction of cerebral cortex activated guanylate cyclase in supernatant of brain, liver, or kidney in the presence of hydroxylamine. The mitochondrial fraction prepared from liver or kidney, in turn, activated soluble guanylate cyclase in brain. Activation of guanylate cyclase by hydroxylamine was compared with that of sodium azide. Azide activated guanylate cyclase in the synaptosomal soluble fraction, while hydroxylamine inhibited it. The particulate fraction preincubated with azide followed by washing did not stimulate guanylate cyclase activity in the absence of azide. The activation of guanylate cyclase by hydroxylamine is not due to a change in the concentration of the substrate GTP, Addition of hydroxylamine did not alter the apparent Km value of guanylate cyclase for GTP. Guanylate cyclase became less dependent on manganese in the presence of hydroxylamine. Thus the activation of guanylate cyclase by hydroxylamine is due to the change in the Vmax of the reaction.", "contents": "Activation of guanylate cyclase in cerebral cortex of rat by hydroxylamine. Hydroxylamine actived guanylate cyclase in particulate fraction of cerebral cortex of rat. Activation was most remarkable in crude mitochondrial fraction. When the crude mitochondrial fraction was subjected to osmotic shock and fractionated, guanylate cyclase activity recovered in the subfractions as assayed with hydroxylamine was only one-third of the starting material. Recombination of the soluble and the particulate fractions, however, restored guanylate cyclase activity to the same level as that of the starting material. When varying quantities of the particulate and soluble fractions were combined, enzyme activity was proportional to the quantity of the soluble fraction. Heating of the soluble or particulate fraction at 55 degrees for 5 min inactivated guanylate cyclase. The heated particulate fraction markedly activated guanylate cyclase activity in the native soluble fraction, while the heated soluble fraction did not stimulate enzyme activity in the particulate. The particulate fraction preincubated with hydroxylamine at 37 degrees for 5 min followed by washing activated guanylate cyclase activity in the soluble fraction in the absence of hydroxylamine. Further fractionation of the crude mitochondrial fraction revealed that the factor(s) needed for the activation by hydroxylamine is associated with the mitochondria. The mitochondrial fraction of cerebral cortex activated guanylate cyclase in supernatant of brain, liver, or kidney in the presence of hydroxylamine. The mitochondrial fraction prepared from liver or kidney, in turn, activated soluble guanylate cyclase in brain. Activation of guanylate cyclase by hydroxylamine was compared with that of sodium azide. Azide activated guanylate cyclase in the synaptosomal soluble fraction, while hydroxylamine inhibited it. The particulate fraction preincubated with azide followed by washing did not stimulate guanylate cyclase activity in the absence of azide. The activation of guanylate cyclase by hydroxylamine is not due to a change in the concentration of the substrate GTP, Addition of hydroxylamine did not alter the apparent Km value of guanylate cyclase for GTP. Guanylate cyclase became less dependent on manganese in the presence of hydroxylamine. Thus the activation of guanylate cyclase by hydroxylamine is due to the change in the Vmax of the reaction."}
{"id": "PMID:13074", "title": "Studies on the cyclic 3':5'-AMP-stimulated pig liver protein kinase reaction with pyruvate kinase as substrate.", "content": "The phosphorylation of pig liver pyruvate kinase by cyclic adenosine 3':5'-monophosphate-dependent protein kinase has been studied. For comparison, mixed histone and a synthetic heptapeptide were also used as substrates. Protein kinase was purified by chromatography on DEAE-cellulose, hydroxyapatite, and Sephadex G-200. The enzyme was stimulated by cyclic AMP with apparent Ka values of 2.5 and 0.8 x 10-7 M for pyruvate kinase and histone substrates, respectively. Divalent cations were essential for the activity of the protein kinase. Variation of the concentration of ATP resulted in approximately straight lines in Lineweaver-Burk plots for the phosphorylation of both pyruvate kinase and mixed histone. The apparent Km values for ATP were 21 and 11 muM, respectively. The phosphorylation rate increased with the concentration of pyruvate kinase even at a concentration of 2 muM pyruvate kinase. At a high ionic strength, the phosphorylation rate of both pyruvate kinase and histone decreased. The phosphorylation rate varied markedly with pH in imidazole/HC1 and Tris/HC1 buffers. At slightly alkaline pH values, pyruvate kinase was phosphorylated at a much higher rate than pH7, but this was not the case for histone. At pH 8.5, the phosphorylation rate of pyruvate kinase was 3.5 times the rate at pH 7, while the corresponding increase for the histone phosphorylation was 50 per cent. In potassium phosphate buffers, the phosphorylation rate of both substrates did not change significantly over the pH range studied. Arrhenius' plots of the protein kinase reaction resulted in a break at about 10 degrees when pyruvate kinase was used as substrate, whereas a straight line was obtained when using histone. The negative allosteric effectors of pyruvate kinase, alanine, and phenylalanine, increased the phosphorylation rate of pyruvate kinase at pH 8 by 50 and 120 per cent, respectively. The same effectors did not influence the phosphorylation rate of mixed histone or a synthetic heptapeptide. It is concluded that the conformations adopted by pyruvate kinase in the presence of allosteric inhibitors make it a better substrate for the protein kinase.", "contents": "Studies on the cyclic 3':5'-AMP-stimulated pig liver protein kinase reaction with pyruvate kinase as substrate. The phosphorylation of pig liver pyruvate kinase by cyclic adenosine 3':5'-monophosphate-dependent protein kinase has been studied. For comparison, mixed histone and a synthetic heptapeptide were also used as substrates. Protein kinase was purified by chromatography on DEAE-cellulose, hydroxyapatite, and Sephadex G-200. The enzyme was stimulated by cyclic AMP with apparent Ka values of 2.5 and 0.8 x 10-7 M for pyruvate kinase and histone substrates, respectively. Divalent cations were essential for the activity of the protein kinase. Variation of the concentration of ATP resulted in approximately straight lines in Lineweaver-Burk plots for the phosphorylation of both pyruvate kinase and mixed histone. The apparent Km values for ATP were 21 and 11 muM, respectively. The phosphorylation rate increased with the concentration of pyruvate kinase even at a concentration of 2 muM pyruvate kinase. At a high ionic strength, the phosphorylation rate of both pyruvate kinase and histone decreased. The phosphorylation rate varied markedly with pH in imidazole/HC1 and Tris/HC1 buffers. At slightly alkaline pH values, pyruvate kinase was phosphorylated at a much higher rate than pH7, but this was not the case for histone. At pH 8.5, the phosphorylation rate of pyruvate kinase was 3.5 times the rate at pH 7, while the corresponding increase for the histone phosphorylation was 50 per cent. In potassium phosphate buffers, the phosphorylation rate of both substrates did not change significantly over the pH range studied. Arrhenius' plots of the protein kinase reaction resulted in a break at about 10 degrees when pyruvate kinase was used as substrate, whereas a straight line was obtained when using histone. The negative allosteric effectors of pyruvate kinase, alanine, and phenylalanine, increased the phosphorylation rate of pyruvate kinase at pH 8 by 50 and 120 per cent, respectively. The same effectors did not influence the phosphorylation rate of mixed histone or a synthetic heptapeptide. It is concluded that the conformations adopted by pyruvate kinase in the presence of allosteric inhibitors make it a better substrate for the protein kinase."}
{"id": "PMID:13075", "title": "Assay and partial characterization of the solubilized cell surface receptor for immunoglobulin E.", "content": "The cell surface component (receptor) which specifically binds immunoglobulin E (IgE) presumably forms an integral part of the functional chain involved in the antigen-induced IgE-mediated degranulation of histamine-containing mast cells and basophils. This paper describes a simple (NH4)2SO4 predipitation assay with which the interaction of IgE with detergent-solubilized receptors can be reproducibly quantitated. Receptor saturation was demonstrated and a linear response to receptor concentration over at least a 30-fold rang obtained. By means of the assay it was shown that (a) all assayable receptors of rat basophil leukemia cells are cell surface expressed; (b) receptor specificity remains intact during solubilization; (c) the binding constants of the solubilized IgE receptors are similar to those determined on intact cells. Utilizing agarose gel filtration, preliminary estimates of the molecular weight of the active free solubilized receptor and of its complex with IgE suggest that the receptor is univalent.", "contents": "Assay and partial characterization of the solubilized cell surface receptor for immunoglobulin E. The cell surface component (receptor) which specifically binds immunoglobulin E (IgE) presumably forms an integral part of the functional chain involved in the antigen-induced IgE-mediated degranulation of histamine-containing mast cells and basophils. This paper describes a simple (NH4)2SO4 predipitation assay with which the interaction of IgE with detergent-solubilized receptors can be reproducibly quantitated. Receptor saturation was demonstrated and a linear response to receptor concentration over at least a 30-fold rang obtained. By means of the assay it was shown that (a) all assayable receptors of rat basophil leukemia cells are cell surface expressed; (b) receptor specificity remains intact during solubilization; (c) the binding constants of the solubilized IgE receptors are similar to those determined on intact cells. Utilizing agarose gel filtration, preliminary estimates of the molecular weight of the active free solubilized receptor and of its complex with IgE suggest that the receptor is univalent."}
{"id": "PMID:13076", "title": "An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase.", "content": "Under anaerobic conditions, cells of Entamoeba histolytica grown with bacteria produce H2 and acetate while cells grown axenically produce neither. Aerobically, acetate is produced and O2 is consumed by amebae from either type of cells. Centrifuged extracts, 2.4 x 106 x g x min, from both types of cells contain pyruvate synthase (EC 1.2.7.1) and an acetate thiokinase which, together, form a system capable of converting pyruvate to acetate. Pyruvate synthase catalyzes the reaction: pyruvate + CoA leads to CO2 + acetyl-CoA + 2E. Electron acceptors which function with this enzyme are FAD, FMN, riboflavin, ferredoxin, and methyl viologen, but not NAD or NADP. The amebal acetate thiokinase catalyzes the reaction acetyl-CoA + ADP + Pi leads to acetate + ATP + CoA. For this apparently new enzyme we suggest the trivial name acetyl-CoA-synthetase (ADP-forming). Extracts from axenic amebae do not contain hydrogenase, but extracts from cells grown with bacteria do. It is postulated that in bacteria-grown amebae electrons generated at the pyruvate synthase step are utilized anaerobically to produce H2 via the hydrogenase and that the acetyl-CoA is converted to acetate in an energy-conserving step catalyzed by amebal acetyl-CoA synthetase. Aerobically, cells grown under either regimen may utilize the energy-conserving pyruvate-to-acetate pathway since O2 then serves as the ultimate electron acceptor.", "contents": "An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase. Under anaerobic conditions, cells of Entamoeba histolytica grown with bacteria produce H2 and acetate while cells grown axenically produce neither. Aerobically, acetate is produced and O2 is consumed by amebae from either type of cells. Centrifuged extracts, 2.4 x 106 x g x min, from both types of cells contain pyruvate synthase (EC 1.2.7.1) and an acetate thiokinase which, together, form a system capable of converting pyruvate to acetate. Pyruvate synthase catalyzes the reaction: pyruvate + CoA leads to CO2 + acetyl-CoA + 2E. Electron acceptors which function with this enzyme are FAD, FMN, riboflavin, ferredoxin, and methyl viologen, but not NAD or NADP. The amebal acetate thiokinase catalyzes the reaction acetyl-CoA + ADP + Pi leads to acetate + ATP + CoA. For this apparently new enzyme we suggest the trivial name acetyl-CoA-synthetase (ADP-forming). Extracts from axenic amebae do not contain hydrogenase, but extracts from cells grown with bacteria do. It is postulated that in bacteria-grown amebae electrons generated at the pyruvate synthase step are utilized anaerobically to produce H2 via the hydrogenase and that the acetyl-CoA is converted to acetate in an energy-conserving step catalyzed by amebal acetyl-CoA synthetase. Aerobically, cells grown under either regimen may utilize the energy-conserving pyruvate-to-acetate pathway since O2 then serves as the ultimate electron acceptor."}
{"id": "PMID:13077", "title": "The purification and characterization of rat liver lysosomal alpha-L-fucosidase.", "content": "The alpha-L-fucosidase from rat liver lysosomes was purified approximately 27,000-fold (from cytoplasmic extract) by a rapid procedure requiring only 7 h anf providing enzyme in a 20 per cent yield. The procedure is based upon affinity chromatography with agarose-epsilon-aminocaproyl-fucosamine. The isolated enzyme was found to be pure by a number of different analytical gel techniques and is essentially free of other lysosomal gylcosidases. The purified enzyme exhibits a positive periodic acid-Schiff stain, suggesting that it is a glycoprotein. The purified enzyme has a pH optimum of 5.7 to 5.9, a Vmax of 27 mumol/min/mg of protein, and a Km of 0.19 mM with p-nitrophenyl alpha-L-fucopyranoside as substrate. L-Fucose was the only possibly physiological effector of the enzyme which was identified; it exhibited a Ki of 1.6 mM, with p-nitrophenyl alpha-L-fucopyranoside as substrate. The enzyme has a subunit molecular weight of approximately 55,000 by Na dodecyl-SO4 electrophoresis in a variety of gel systems. The molecular weight of the native enzyme was indicated to be approximately 160,000 by sucrose density centrifugation, 300,000 by molecular sieve chromatography on Sephadex G-200, and 217,000 by sedimentation equilibrium centrifugation. The weight of evidence suggests that the enzyme is a tetramer. Incubation on the absence of sulfhydryl reagents under appropriate conditions generates a second alpha-L-fucosidase activity band on gels corresponding to a molecular weight of approximately 40,000 to 50,000. This result suggests that the subunit is relatively stable and may reassociate to form active enzyme. Alpha-L-Fucosidase requires a high concentration of protein and the presence of a sulfhydryl reagent for stabilization. It is rapidly inactivated by p-chloromercuriphenyl sulfonic acid, this inactivation being rapidly reversible by the addition of 10 mM 2-mercaptoethanol. The enzyme catalyzed the hydrolysis of 1 leads to 2, 1 leads to 3, and 1 leads to 4 fucosyl linkages and was found to be active on glycopeptides but not on native glycoproteins. The amino acid and carbohydrate composition of the enzyme was determined. The native enzyme contains the following sugars (residues per tetramer): fucose (3.5), mannose (32), galactose (8), glucose (9), glucosamine (32), and sialic acid (8). Rat liver lysosomal alpha-glucosidase, also produced in the rapid isolation procedure described herein, contained less than 0.1 residue of sialic acid per subunit.", "contents": "The purification and characterization of rat liver lysosomal alpha-L-fucosidase. The alpha-L-fucosidase from rat liver lysosomes was purified approximately 27,000-fold (from cytoplasmic extract) by a rapid procedure requiring only 7 h anf providing enzyme in a 20 per cent yield. The procedure is based upon affinity chromatography with agarose-epsilon-aminocaproyl-fucosamine. The isolated enzyme was found to be pure by a number of different analytical gel techniques and is essentially free of other lysosomal gylcosidases. The purified enzyme exhibits a positive periodic acid-Schiff stain, suggesting that it is a glycoprotein. The purified enzyme has a pH optimum of 5.7 to 5.9, a Vmax of 27 mumol/min/mg of protein, and a Km of 0.19 mM with p-nitrophenyl alpha-L-fucopyranoside as substrate. L-Fucose was the only possibly physiological effector of the enzyme which was identified; it exhibited a Ki of 1.6 mM, with p-nitrophenyl alpha-L-fucopyranoside as substrate. The enzyme has a subunit molecular weight of approximately 55,000 by Na dodecyl-SO4 electrophoresis in a variety of gel systems. The molecular weight of the native enzyme was indicated to be approximately 160,000 by sucrose density centrifugation, 300,000 by molecular sieve chromatography on Sephadex G-200, and 217,000 by sedimentation equilibrium centrifugation. The weight of evidence suggests that the enzyme is a tetramer. Incubation on the absence of sulfhydryl reagents under appropriate conditions generates a second alpha-L-fucosidase activity band on gels corresponding to a molecular weight of approximately 40,000 to 50,000. This result suggests that the subunit is relatively stable and may reassociate to form active enzyme. Alpha-L-Fucosidase requires a high concentration of protein and the presence of a sulfhydryl reagent for stabilization. It is rapidly inactivated by p-chloromercuriphenyl sulfonic acid, this inactivation being rapidly reversible by the addition of 10 mM 2-mercaptoethanol. The enzyme catalyzed the hydrolysis of 1 leads to 2, 1 leads to 3, and 1 leads to 4 fucosyl linkages and was found to be active on glycopeptides but not on native glycoproteins. The amino acid and carbohydrate composition of the enzyme was determined. The native enzyme contains the following sugars (residues per tetramer): fucose (3.5), mannose (32), galactose (8), glucose (9), glucosamine (32), and sialic acid (8). Rat liver lysosomal alpha-glucosidase, also produced in the rapid isolation procedure described herein, contained less than 0.1 residue of sialic acid per subunit."}
{"id": "PMID:13078", "title": "Investigation of the subunit interactions in malate dehydrogenase.", "content": "The dissociations of porcine heart mitochondrial, bovine heart mitochondrial, and porcine heart cytoplasmic malate dehydrogenase dimers (L-malate: NAD+oxidoreductase, EC 1.1.1.37) have been examined by Sephadex G-100 gel filtration chromatography and sedimentation velocity ultracentrifugation. The porcine mitochondrial enzyme was found to chromatograph as subunits when applied to a gel filtration column at a concentration of .02 muM or less at pH 7.0. The presence of coenzymes shifted the dissociation equilibrium at low enzyme concentrations in favor of dimer formation. Monomer formation was also favored when procine mitochondrial enzyme was incubated at pH 5.0 even at concentrations as high as 120 muM. This shift in equilibrium has been correlated with the increased rate and specificity of sulfhydryl residue modification with N-ethylmaleimide at pH 5.0 (Gregory, E.M., Yost, F.J.,Jr., Rohrbach, M.S., and Harrison, J.H. (1971)J. Biol. Chem. 246, 5491-5497). Bovine mitochondrial enzyme did not exhibit a concentration-dependent disociation under the conditions examined. However, at pH5.0 monomer formation was favored, and correlations could again be drawn with sulfhydryl residue modification (Gregory, E.M. (1975)J.Biol. Chem. 250, 5470-5474). In both mitochondrial enzymes, coenzyme binding was found capable of overcoming the effects of pH on the dissociation equilibrium, and dimer formation was favored. Unlike either of the above mentioned enzymes, porcine cytoplasmic malate dehydrogenase did not dissociate into its monomeric form under any conditions investigated.", "contents": "Investigation of the subunit interactions in malate dehydrogenase. The dissociations of porcine heart mitochondrial, bovine heart mitochondrial, and porcine heart cytoplasmic malate dehydrogenase dimers (L-malate: NAD+oxidoreductase, EC 1.1.1.37) have been examined by Sephadex G-100 gel filtration chromatography and sedimentation velocity ultracentrifugation. The porcine mitochondrial enzyme was found to chromatograph as subunits when applied to a gel filtration column at a concentration of .02 muM or less at pH 7.0. The presence of coenzymes shifted the dissociation equilibrium at low enzyme concentrations in favor of dimer formation. Monomer formation was also favored when procine mitochondrial enzyme was incubated at pH 5.0 even at concentrations as high as 120 muM. This shift in equilibrium has been correlated with the increased rate and specificity of sulfhydryl residue modification with N-ethylmaleimide at pH 5.0 (Gregory, E.M., Yost, F.J.,Jr., Rohrbach, M.S., and Harrison, J.H. (1971)J. Biol. Chem. 246, 5491-5497). Bovine mitochondrial enzyme did not exhibit a concentration-dependent disociation under the conditions examined. However, at pH5.0 monomer formation was favored, and correlations could again be drawn with sulfhydryl residue modification (Gregory, E.M. (1975)J.Biol. Chem. 250, 5470-5474). In both mitochondrial enzymes, coenzyme binding was found capable of overcoming the effects of pH on the dissociation equilibrium, and dimer formation was favored. Unlike either of the above mentioned enzymes, porcine cytoplasmic malate dehydrogenase did not dissociate into its monomeric form under any conditions investigated."}
{"id": "PMID:13079", "title": "Tuna cytochrome c at 2.0 A resolution. I. Ferricytochrome structure analysis.", "content": "The crystal structure of oxidized cytochrome c from tuna hearts has been solved by x-ray diffraction to a resolution of 2.0 A, using four isomorphous heavy atom derivatives. The crystals, space group P43, have 2 independent cytochrome molecules in the asymmetric repeating unit. No significant difference is seen between these 2 molecules, aside from conformations of a few surface side chains. The molecular folding observed is essentially that reported for tuna ferrocytochrome c. In particular, the ring of phenylalanine 83 lies against the heme group and closes the heme crevice, and is not swung out into the surroundings as had been believed from the 2.8 A horse ferricytochrome c structure.", "contents": "Tuna cytochrome c at 2.0 A resolution. I. Ferricytochrome structure analysis. The crystal structure of oxidized cytochrome c from tuna hearts has been solved by x-ray diffraction to a resolution of 2.0 A, using four isomorphous heavy atom derivatives. The crystals, space group P43, have 2 independent cytochrome molecules in the asymmetric repeating unit. No significant difference is seen between these 2 molecules, aside from conformations of a few surface side chains. The molecular folding observed is essentially that reported for tuna ferrocytochrome c. In particular, the ring of phenylalanine 83 lies against the heme group and closes the heme crevice, and is not swung out into the surroundings as had been believed from the 2.8 A horse ferricytochrome c structure."}
{"id": "PMID:13081", "title": "Some physicochemical properties of plasma membrane vesicles.", "content": "The plasma membranes of many animal cells can be disrupted into small sealed vesicles that can be purified centrifugally and utilized for studies on membrane transport. The vesicles behave as micro-osmometers. However, the presence of charges fixed at the internal and external surfaces of the membrane walls produce pH levels at these surfaces that deviate considerably from bulk pH. Transverse symmetry of charge distribution further leads to transverse asymmetry of surface pH. Finally, charges fixed at the internal membrane surface produced significant Donnan osmotic effects that depend upon membrane composition and ionic environment.", "contents": "Some physicochemical properties of plasma membrane vesicles. The plasma membranes of many animal cells can be disrupted into small sealed vesicles that can be purified centrifugally and utilized for studies on membrane transport. The vesicles behave as micro-osmometers. However, the presence of charges fixed at the internal and external surfaces of the membrane walls produce pH levels at these surfaces that deviate considerably from bulk pH. Transverse symmetry of charge distribution further leads to transverse asymmetry of surface pH. Finally, charges fixed at the internal membrane surface produced significant Donnan osmotic effects that depend upon membrane composition and ionic environment."}
{"id": "PMID:13082", "title": "A novel mechanism for group translocation: substrate-product reutilization by gamma-glutamyl transpeptidase in peptide and amino acid transport.", "content": "Gamma-glutamyl transpeptidase (gamma-GTP) is suggested to act as a carrier in the group translocation of oligopeptides and possibly some amino acids across cellular membranes. It is proposed that the process may involve the repetitive transfer of gamma-glutamyl groups to acceptor peptides which are being translocated from the exterior of the cell to its interior. After group translocation of the peptides has occurred with concomitant formation of gamma-glutamyl peptide products, it is suggested that the products might then be utilized as substrate for the enzyme in order to permit the translocation of other peptides from the exterior. The system is economical and requires only that it be primed with an appropriate source of gamma-glutamyl peptides, such as glutathione. In contrast to most group translocation systems previously described, substrate-product reutilization by gamma-GTP would not be expected to accumulate peptides against a concentration gradient. Mechanisms for maintaining low intracellular concentrations of the translocated peptides are described. Studies on acceptor substrate specificity of gamma-GTP from bovine choroid plexus and rat kidney show some glycyl peptides are much better substrates than free amino acids in accord with the proposal that gamma-GTP might be primarily involved in peptide translocation. Both kinetic and topological evidence support the suggestion that repetitive transfer of gamma-glutamyl moieties by gamma-GTP could occur during group translocation of peptides and possibly some amino acids.", "contents": "A novel mechanism for group translocation: substrate-product reutilization by gamma-glutamyl transpeptidase in peptide and amino acid transport. Gamma-glutamyl transpeptidase (gamma-GTP) is suggested to act as a carrier in the group translocation of oligopeptides and possibly some amino acids across cellular membranes. It is proposed that the process may involve the repetitive transfer of gamma-glutamyl groups to acceptor peptides which are being translocated from the exterior of the cell to its interior. After group translocation of the peptides has occurred with concomitant formation of gamma-glutamyl peptide products, it is suggested that the products might then be utilized as substrate for the enzyme in order to permit the translocation of other peptides from the exterior. The system is economical and requires only that it be primed with an appropriate source of gamma-glutamyl peptides, such as glutathione. In contrast to most group translocation systems previously described, substrate-product reutilization by gamma-GTP would not be expected to accumulate peptides against a concentration gradient. Mechanisms for maintaining low intracellular concentrations of the translocated peptides are described. Studies on acceptor substrate specificity of gamma-GTP from bovine choroid plexus and rat kidney show some glycyl peptides are much better substrates than free amino acids in accord with the proposal that gamma-GTP might be primarily involved in peptide translocation. Both kinetic and topological evidence support the suggestion that repetitive transfer of gamma-glutamyl moieties by gamma-GTP could occur during group translocation of peptides and possibly some amino acids."}
{"id": "PMID:13084", "title": "The separation of nonapeptides by reversed-phase high-performance liquid chromatography.", "content": "The separation properties of five nonapeptides on commercial reversed-phase materials have been investigated and the effects of pH, salt concentration and solvent composition have been studied. With appropriate variation of the pH and salt concentration in the mobile phase, it is possible to resolve all of the peptides investigated and their by-products. Mixtures of water and organic solvents (acetonitrile, dioxan, methanol and n-propanol) have been used. The choice of the organic solvent does not strongly influence the separation pattern. The simplicity, speed and quality of the separations and the favourable detection limits (ca. 30 ng) at 220 nm render this technique suitable to routine quantitative analysis.", "contents": "The separation of nonapeptides by reversed-phase high-performance liquid chromatography. The separation properties of five nonapeptides on commercial reversed-phase materials have been investigated and the effects of pH, salt concentration and solvent composition have been studied. With appropriate variation of the pH and salt concentration in the mobile phase, it is possible to resolve all of the peptides investigated and their by-products. Mixtures of water and organic solvents (acetonitrile, dioxan, methanol and n-propanol) have been used. The choice of the organic solvent does not strongly influence the separation pattern. The simplicity, speed and quality of the separations and the favourable detection limits (ca. 30 ng) at 220 nm render this technique suitable to routine quantitative analysis."}
{"id": "PMID:13085", "title": "Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis.", "content": "It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide. Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity. Demethylglycodiazin (2-benzolsulfonamid--5-(beta-hydroxyethoxy)-pyrimidin), which did not inhibit endogenous ketogenesis in isolated liver cells, did not affect lysosomal lipase activity. The lysosomotropic drug chloroquine was markedly antiketogenic when tested in liver cells. The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis.", "contents": "Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis. It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide. Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity. Demethylglycodiazin (2-benzolsulfonamid--5-(beta-hydroxyethoxy)-pyrimidin), which did not inhibit endogenous ketogenesis in isolated liver cells, did not affect lysosomal lipase activity. The lysosomotropic drug chloroquine was markedly antiketogenic when tested in liver cells. The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis."}
{"id": "PMID:13086", "title": "Ectopic beta-adrenergic receptor binding sites. possible molecular basis of aberrant catecholamine responsiveness of an adrenocortical tumor adenylate cyclase.", "content": "The molecular basis for the aberrant catecholamine responsiveness of the adenylate cyclase of adrenocortical carcinoma 494 was explored. The adenylate cyclase of this corticosteroid-producing, transplanted, adrenal cancer of the rat was stimulated not only by adrenocorticotropic hormone and fluoride, but also by the beta-adrenergic agonist, isoproterenol. The adenylate cyclase of normal adrenal tissue was unresponsive to isoproterenol. Direct binding studies with the specific high affinity B-adrenergic ligand, (-)[3H]dihydroalprenolol, demonstrated the pressure of 0.094 pmol of specific binding sites per milligram of tumor membrane protein. By contrast, normal adrenal membranes contained too few binding sites to accurately measure and study using these techniques. The tumor binding sites had high affinity for (-)[3H] dihydroalprenolol with an equilibrium dissociation constant of 2.1 nM. Adrenergic agonists competed for the binding sites in an order of potency, [(-) isoproterenol greater than (-) epinephrine (-) norepinephrine], paralleling their order of potency as beta-adrenergic agonists. The beta-adrenergic antagonist, (-) propranolol, competed for binding, causing half-mzximal inhibition of specific binding at a concentration of 6 nM. The alpha-adrenergic antagonist, phentolamine, and several catecholamine metabolites and precursors did not effectively compete for the binding sites at high concentrations. Binding was stereospecific, the (+) stereoisomers of beta-adrenergic agonists and antagonists requiring 40- to 300-fold higher concentrations than the corresponding (-) stereoisomers to half maximally inhibit (-) [3H] dihydroalprenolol binding. These results indicate that adrenocortical carcinoma 494 membranes contain beta-adrenergic receptor-binding sites which are not normally present in membranes of adrenal tissue. These ectopic beta-adrenergic receptors presumably confer on the neoplastic tissue the catecholamine sensitivity of its adenylate cyclase.", "contents": "Ectopic beta-adrenergic receptor binding sites. possible molecular basis of aberrant catecholamine responsiveness of an adrenocortical tumor adenylate cyclase. The molecular basis for the aberrant catecholamine responsiveness of the adenylate cyclase of adrenocortical carcinoma 494 was explored. The adenylate cyclase of this corticosteroid-producing, transplanted, adrenal cancer of the rat was stimulated not only by adrenocorticotropic hormone and fluoride, but also by the beta-adrenergic agonist, isoproterenol. The adenylate cyclase of normal adrenal tissue was unresponsive to isoproterenol. Direct binding studies with the specific high affinity B-adrenergic ligand, (-)[3H]dihydroalprenolol, demonstrated the pressure of 0.094 pmol of specific binding sites per milligram of tumor membrane protein. By contrast, normal adrenal membranes contained too few binding sites to accurately measure and study using these techniques. The tumor binding sites had high affinity for (-)[3H] dihydroalprenolol with an equilibrium dissociation constant of 2.1 nM. Adrenergic agonists competed for the binding sites in an order of potency, [(-) isoproterenol greater than (-) epinephrine (-) norepinephrine], paralleling their order of potency as beta-adrenergic agonists. The beta-adrenergic antagonist, (-) propranolol, competed for binding, causing half-mzximal inhibition of specific binding at a concentration of 6 nM. The alpha-adrenergic antagonist, phentolamine, and several catecholamine metabolites and precursors did not effectively compete for the binding sites at high concentrations. Binding was stereospecific, the (+) stereoisomers of beta-adrenergic agonists and antagonists requiring 40- to 300-fold higher concentrations than the corresponding (-) stereoisomers to half maximally inhibit (-) [3H] dihydroalprenolol binding. These results indicate that adrenocortical carcinoma 494 membranes contain beta-adrenergic receptor-binding sites which are not normally present in membranes of adrenal tissue. These ectopic beta-adrenergic receptors presumably confer on the neoplastic tissue the catecholamine sensitivity of its adenylate cyclase."}
{"id": "PMID:13087", "title": "Patients' expectancies and hospital outcome.", "content": "Although it is widely held that patients' expectancies for therapeutic gain are related causally to treatment outcome, a recent review of expectancy research found scant evidence for the hypothesized expectancy-outcome relationship. Supportive findings were reported only in studies with serious methodological weaknesses. This study tested the relationship between the prognostic expectancies of hospitalized schizophrenic patients and several objective measures of hospital outcome. It also tested the hypothesis that expectancies may bear primarily a predictive, not causal, relationship to outcome. Multiple regression analyses found patients' expectancies to be correlated significantly with 8 of 15 measures of posthospital adjustment and with 14 of 15 measures of prehospital adjustment. The findings supported the expectancy-outcome relationship and also were consistent with a predictive interpretation of patients' expectancies.", "contents": "Patients' expectancies and hospital outcome. Although it is widely held that patients' expectancies for therapeutic gain are related causally to treatment outcome, a recent review of expectancy research found scant evidence for the hypothesized expectancy-outcome relationship. Supportive findings were reported only in studies with serious methodological weaknesses. This study tested the relationship between the prognostic expectancies of hospitalized schizophrenic patients and several objective measures of hospital outcome. It also tested the hypothesis that expectancies may bear primarily a predictive, not causal, relationship to outcome. Multiple regression analyses found patients' expectancies to be correlated significantly with 8 of 15 measures of posthospital adjustment and with 14 of 15 measures of prehospital adjustment. The findings supported the expectancy-outcome relationship and also were consistent with a predictive interpretation of patients' expectancies."}
{"id": "PMID:13088", "title": "Alpha wave biofeedback training therapy in alcoholics.", "content": "This investigation evaluated the therapeutic efficacy of alpha-wave biofeedback treatment for alcoholics. Twenty-five Ss were compared to a matched control group before and after administration of a 3-week alpha-wave biofeedback regimen on a wide variety of criteria that included State-Trait Anxiety, the MMPI, Multiple Affect Adjective Check List, Zuckerman's Sensation Seeking Scale, Watson's Anhedonia Scale, the Brief Psychiatric Rating Scale, and baseline alpha. The experimental Ss received 10 hour-long alpha training sessions. The experimentals showed more improvement than did controls on alpha production and two anxiety measure. Contradictory results appeared on two suspicion/paranoia measures. Alpha training appeared useful in the treatment of anxiety, but not other problems. However, the absence of significant correlations between amount of change on alpha and the anxiety measures suggests that the improvement may be due to a placebo effect.", "contents": "Alpha wave biofeedback training therapy in alcoholics. This investigation evaluated the therapeutic efficacy of alpha-wave biofeedback treatment for alcoholics. Twenty-five Ss were compared to a matched control group before and after administration of a 3-week alpha-wave biofeedback regimen on a wide variety of criteria that included State-Trait Anxiety, the MMPI, Multiple Affect Adjective Check List, Zuckerman's Sensation Seeking Scale, Watson's Anhedonia Scale, the Brief Psychiatric Rating Scale, and baseline alpha. The experimental Ss received 10 hour-long alpha training sessions. The experimentals showed more improvement than did controls on alpha production and two anxiety measure. Contradictory results appeared on two suspicion/paranoia measures. Alpha training appeared useful in the treatment of anxiety, but not other problems. However, the absence of significant correlations between amount of change on alpha and the anxiety measures suggests that the improvement may be due to a placebo effect."}
{"id": "PMID:13089", "title": "Steady-state bioavailability of two clorazepate dipotassium dosage forms.", "content": "A specially designed tablet dosage form of the benzodiazepine clorazepate dipotassium (Tranxene) was developed for once-a-day administration. The drug was administered at a dose of 22.5 mg as (1) the tablet, (2) three 7.5 mg capsules, or (3) one 7.5-mg capsule given every 6 hours. Peak serum levels from the tablet were intermediate between those of the single- and divided-dose capsule regimens. The desired decrease in magnitude of peak levels was obtained without affecting the extent of absorption. Pharmacokinetic analysis of the data according to a two-compartment open model with first-order absorption indicated that the serum half-life (t0.5beta) of nordiazepam, the major biotransformation product present in serum, was about 48 hours and served as a basis for the design of a multiple-dose steady-state study. Multiple-dose administration of the tablet and divided-capsule regimen to two groups of subjects for ten days indicated each dosage form yielded similar minimum steady-state serum levels of about 0.6 micrograms/ml which plateaued following seven days of drug administration. The dosage forms were crossed over between the groups on day 11 and administered for an additional four days. The minimum serum levels obtained with the tablet and capsule were not statistically different. Additionally, the peak serum level and area under the curve (pi=24 hours) at steady state were equivalent between the dosage forms. Good agreement was obtained between model-predicted and observed serum levels during multiple-dose administration for both the tablet and capsule regimens. The serum half-life of nordiazepam following 14 days of clorazepate dipotassium administration was similar to that found after a single dose. These results indicate that a single daily dose of drug as the tablet produced serum levels equivalent to a divided-capsule regimen.", "contents": "Steady-state bioavailability of two clorazepate dipotassium dosage forms. A specially designed tablet dosage form of the benzodiazepine clorazepate dipotassium (Tranxene) was developed for once-a-day administration. The drug was administered at a dose of 22.5 mg as (1) the tablet, (2) three 7.5 mg capsules, or (3) one 7.5-mg capsule given every 6 hours. Peak serum levels from the tablet were intermediate between those of the single- and divided-dose capsule regimens. The desired decrease in magnitude of peak levels was obtained without affecting the extent of absorption. Pharmacokinetic analysis of the data according to a two-compartment open model with first-order absorption indicated that the serum half-life (t0.5beta) of nordiazepam, the major biotransformation product present in serum, was about 48 hours and served as a basis for the design of a multiple-dose steady-state study. Multiple-dose administration of the tablet and divided-capsule regimen to two groups of subjects for ten days indicated each dosage form yielded similar minimum steady-state serum levels of about 0.6 micrograms/ml which plateaued following seven days of drug administration. The dosage forms were crossed over between the groups on day 11 and administered for an additional four days. The minimum serum levels obtained with the tablet and capsule were not statistically different. Additionally, the peak serum level and area under the curve (pi=24 hours) at steady state were equivalent between the dosage forms. Good agreement was obtained between model-predicted and observed serum levels during multiple-dose administration for both the tablet and capsule regimens. The serum half-life of nordiazepam following 14 days of clorazepate dipotassium administration was similar to that found after a single dose. These results indicate that a single daily dose of drug as the tablet produced serum levels equivalent to a divided-capsule regimen."}
{"id": "PMID:13090", "title": "A double-blind evaluation of the nocturnal antisecretory effects of anisotropine methylbromide in man. Dose response and duration of action studies.", "content": "The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without significantly influencing heart rate, blood pressure, visual acuity, or visual accommodation. The duration of action of large doses was then evaluated in fasted and nonfasted subjects. A single dose reduced acid secretion for up to 8 hours, eliminating the nocturnal elevation of acid secretion characteristic of the normal circadian pattern. Near visual acuity and accommodation decreased, an effect more pronounced in fasted subjects, but the magnitude of visual impairment was small. These findings provide the basis for a controlled trial of high-dose nighttime therapy in peptic ulcer disease.", "contents": "A double-blind evaluation of the nocturnal antisecretory effects of anisotropine methylbromide in man. Dose response and duration of action studies. The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without significantly influencing heart rate, blood pressure, visual acuity, or visual accommodation. The duration of action of large doses was then evaluated in fasted and nonfasted subjects. A single dose reduced acid secretion for up to 8 hours, eliminating the nocturnal elevation of acid secretion characteristic of the normal circadian pattern. Near visual acuity and accommodation decreased, an effect more pronounced in fasted subjects, but the magnitude of visual impairment was small. These findings provide the basis for a controlled trial of high-dose nighttime therapy in peptic ulcer disease."}
{"id": "PMID:13093", "title": "The use of behavior modification techniques to successfully manage the child dental patient.", "content": "Techniques of desensitization, modeling, and contingency management that can be used in the dental office for reducing anxiety and encouraging appropriate behavior in children are discussed. The \"tell, show and do\" approach is one desensitization technique easily applied in the private practice. Language should be at the child's level of understanding. An older sibling will frequently serve as an excellent model for a fearful child. Social reinforcers-a handshake, a smile, or praise-should be dispensed throughout dental treatment. Rewards should only follow desired behavior.", "contents": "The use of behavior modification techniques to successfully manage the child dental patient. Techniques of desensitization, modeling, and contingency management that can be used in the dental office for reducing anxiety and encouraging appropriate behavior in children are discussed. The \"tell, show and do\" approach is one desensitization technique easily applied in the private practice. Language should be at the child's level of understanding. An older sibling will frequently serve as an excellent model for a fearful child. Social reinforcers-a handshake, a smile, or praise-should be dispensed throughout dental treatment. Rewards should only follow desired behavior."}
{"id": "PMID:13094", "title": "Bronchodilating activity of an H1 blocker, chlorpheniramine.", "content": "The purpose of this study was to test the hypothesis that chlorpheniramine (CP), and H1 blocker, can cause bronchodilatation if administered intravenously (iv) and in higher doses than those currently prescribed. In 10 subjects with allergic asthma, forced expiratory flows (FEF) were recorded on different days, at comparable baseline values, before and up to 5 hr after administration of 8 mg per os (po) chlorpheniramine, 10 mg iv CP (repeated twice), 5.5 mg/kg iv aminophylline, and 30 mg po butabarbital as well as during a day without drug. Chlorpheniramine administered intravenously produced reproducible increases (+ delta) in FEF, starting at 15 min, peaking at 120 min, and still persisting at 5 hr; the peak + delta averaged 15% for FEV1 and 27% to 53% for flows at low lung volume. FEF showed a comparable + delta after aminophylline, a smaller + delta after orally administered chlorpheniramine and no significant + delta during butabarbital or control sessions. The ratio change over time/variability was higher for FEV1, FEF50%, and FEF25%-75% than for the remaining parameters. In six subjects a double-blind study (chlorpheniramine vs. saline solution) confirmed the effectiveness of the doses administered in the open study. In three subjects, 10 mg iv chlorpheniramine was given at four different baseline values; the highest + delta occurred when the basal FEV1 was approximately 50% of the predicted value and the basal FEF at low lung volume 30% to 40% of the predicted value. In two subjects, log dose-response curves to 2.5, 5.0, and 10.0 mg iv chlorpheniramine were obtained by using FEV1, FEF50%, and FEF25%-75%. Thus chlorpheniramine in high iv doses can dilate the bronchi, the + delta FEF depending on the dose, the percent of the predicted basal FEF value, and \"individual\" responsiveness. Withing the dose range used, bronchodilatation to chlorpheniramine and aminophylline administered intravenously was best detected by FEV1, FEF50%, and FEF25%-75%.", "contents": "Bronchodilating activity of an H1 blocker, chlorpheniramine. The purpose of this study was to test the hypothesis that chlorpheniramine (CP), and H1 blocker, can cause bronchodilatation if administered intravenously (iv) and in higher doses than those currently prescribed. In 10 subjects with allergic asthma, forced expiratory flows (FEF) were recorded on different days, at comparable baseline values, before and up to 5 hr after administration of 8 mg per os (po) chlorpheniramine, 10 mg iv CP (repeated twice), 5.5 mg/kg iv aminophylline, and 30 mg po butabarbital as well as during a day without drug. Chlorpheniramine administered intravenously produced reproducible increases (+ delta) in FEF, starting at 15 min, peaking at 120 min, and still persisting at 5 hr; the peak + delta averaged 15% for FEV1 and 27% to 53% for flows at low lung volume. FEF showed a comparable + delta after aminophylline, a smaller + delta after orally administered chlorpheniramine and no significant + delta during butabarbital or control sessions. The ratio change over time/variability was higher for FEV1, FEF50%, and FEF25%-75% than for the remaining parameters. In six subjects a double-blind study (chlorpheniramine vs. saline solution) confirmed the effectiveness of the doses administered in the open study. In three subjects, 10 mg iv chlorpheniramine was given at four different baseline values; the highest + delta occurred when the basal FEV1 was approximately 50% of the predicted value and the basal FEF at low lung volume 30% to 40% of the predicted value. In two subjects, log dose-response curves to 2.5, 5.0, and 10.0 mg iv chlorpheniramine were obtained by using FEV1, FEF50%, and FEF25%-75%. Thus chlorpheniramine in high iv doses can dilate the bronchi, the + delta FEF depending on the dose, the percent of the predicted basal FEF value, and \"individual\" responsiveness. Withing the dose range used, bronchodilatation to chlorpheniramine and aminophylline administered intravenously was best detected by FEV1, FEF50%, and FEF25%-75%."}
{"id": "PMID:13122", "title": "In situ localization of galactosyltransferase in surface mucous cells of the rat stomach.", "content": "Cryostate sections of the rat stomach fundus were incubated in the presence of uridine 5'-diphosphate-[3H]-galactose. The radioactivity in the surface mucous epithelial cells was shown by autoradiography to be specifically incorporated into a supranuclear area, the area where in these cells the Glogi system is situated. The incorporation lasted only 5-6 min and was Mn++ dependent. Galactose was probably incorporated into a beta-glycosidic bond.", "contents": "In situ localization of galactosyltransferase in surface mucous cells of the rat stomach. Cryostate sections of the rat stomach fundus were incubated in the presence of uridine 5'-diphosphate-[3H]-galactose. The radioactivity in the surface mucous epithelial cells was shown by autoradiography to be specifically incorporated into a supranuclear area, the area where in these cells the Glogi system is situated. The incorporation lasted only 5-6 min and was Mn++ dependent. Galactose was probably incorporated into a beta-glycosidic bond."}
{"id": "PMID:13123", "title": "Neutralization kinetics studies with type SAT2 foot-and-mouth disease virus strains. 1. Factors that influence the rate and pattern of neutralization.", "content": "A study of the kinetics of inactivation of foot-and-mouth disease virus type SAT 2 strains revealed that in most cases the rate of neutralization was not rectilinear. Deviations from first-order kinetics observed represented biphasic or parabolic and stepwise reactions. The initial rate was rapid and showed no lag phase or shoulder. The effects of deviations from linearity could be minimized by dilution of antiserum to a suitable extent. Treatment of virus-antibody mixtures with anti-species globulin resulted in enhancement of the rate of neutralization of homologous and heterologous reactions without significantly altering the relation between the two. This treatment also considerably reduced the amount of the persistent fraction. In attempt to disaggregate virus it was observed that sodium dodecyl sulphate inhibited neutralization of virus by specific antiserum.", "contents": "Neutralization kinetics studies with type SAT2 foot-and-mouth disease virus strains. 1. Factors that influence the rate and pattern of neutralization. A study of the kinetics of inactivation of foot-and-mouth disease virus type SAT 2 strains revealed that in most cases the rate of neutralization was not rectilinear. Deviations from first-order kinetics observed represented biphasic or parabolic and stepwise reactions. The initial rate was rapid and showed no lag phase or shoulder. The effects of deviations from linearity could be minimized by dilution of antiserum to a suitable extent. Treatment of virus-antibody mixtures with anti-species globulin resulted in enhancement of the rate of neutralization of homologous and heterologous reactions without significantly altering the relation between the two. This treatment also considerably reduced the amount of the persistent fraction. In attempt to disaggregate virus it was observed that sodium dodecyl sulphate inhibited neutralization of virus by specific antiserum."}
{"id": "PMID:13124", "title": "Interaction of erythrocytes with human serum proteins. I. Analysis of the effect of pH and ionic strength of the medium.", "content": "The effect of ionic parameters of the medium (pH and ionic strength) on the processes of interaction of tannin-treated erythrocytes and the protein fractions of human serum (macroglobulins, microglobulins and albumin) was studied in factorial experiments. Complex effect of these parametres on the processes under investigation and optimum conditions of erythrocyte sensitization were established. Subsequent fixation of antibodies by the erythrocyte diagnostic and their agglutinating activity are manifested in different mannera depending on the conditions of preceding sensitization. Important peculiarities were discovered in the mechanism of interaction between the erythrocytes and various serum proteins. The obtained results should be taken into account in the production of erythrocyte antigen and antibody diagnosticums.", "contents": "Interaction of erythrocytes with human serum proteins. I. Analysis of the effect of pH and ionic strength of the medium. The effect of ionic parameters of the medium (pH and ionic strength) on the processes of interaction of tannin-treated erythrocytes and the protein fractions of human serum (macroglobulins, microglobulins and albumin) was studied in factorial experiments. Complex effect of these parametres on the processes under investigation and optimum conditions of erythrocyte sensitization were established. Subsequent fixation of antibodies by the erythrocyte diagnostic and their agglutinating activity are manifested in different mannera depending on the conditions of preceding sensitization. Important peculiarities were discovered in the mechanism of interaction between the erythrocytes and various serum proteins. The obtained results should be taken into account in the production of erythrocyte antigen and antibody diagnosticums."}
{"id": "PMID:13125", "title": "Immunofluorescence using dichlorotriazinylaminofluorescein (DTAF). I. Preparation and fractionation of labelled IgG.", "content": "Dichlorotriazinylaminofluorescein (DTAF), the product of the reaction of aminofluorescein with cyanuric chloride, is an effective reagent for conjugating fluorescein to immunnoglobulins. DTAF has absorption and emission properties nearly identical to fluoresceinisothiocyanate (FITC) and DTAF and FITC-labelled antibodies are similar in terms of preparation and specificity of immlnofluorescence. However, DTAF is superior to FITC with regard to cost, purity and stability. Also, DTAF-labelled rabbit IgG conjugates can by quickly and efficientyly fractionated by simple ammonium sulfate precipitation procedures to yield preparations free of both over- and under-conjugated material. In addition, over-conjugated protein can be readily removed from DTAF:IgG conjugates by appropriate adjustment of pH and temperature.", "contents": "Immunofluorescence using dichlorotriazinylaminofluorescein (DTAF). I. Preparation and fractionation of labelled IgG. Dichlorotriazinylaminofluorescein (DTAF), the product of the reaction of aminofluorescein with cyanuric chloride, is an effective reagent for conjugating fluorescein to immunnoglobulins. DTAF has absorption and emission properties nearly identical to fluoresceinisothiocyanate (FITC) and DTAF and FITC-labelled antibodies are similar in terms of preparation and specificity of immlnofluorescence. However, DTAF is superior to FITC with regard to cost, purity and stability. Also, DTAF-labelled rabbit IgG conjugates can by quickly and efficientyly fractionated by simple ammonium sulfate precipitation procedures to yield preparations free of both over- and under-conjugated material. In addition, over-conjugated protein can be readily removed from DTAF:IgG conjugates by appropriate adjustment of pH and temperature."}
{"id": "PMID:13126", "title": "Isolation of anti-haemagglutinin antibodies with an influenza A virus immunoadsorbent.", "content": "The X-31 strain of influenza A (H3N2) virus has been covalently bound to CNBr activated agarose for the separation of anti-haemagglutinin antibodies. The virus immunoadsorbent was used repeatedly under high ionic strength alkali buffer and acid conditions without altering appreciably its antibody binding capacity. Sequential elution of bound anti-haemagglutinin antibodies with increasing concentrations of sodium iodide has enabled the physical separation of antibody populations with low and high avidity for the virus immunoadsorbent. In haemagglutination inhibition (h1) assays, the less avid population reacted only with the homologous X-31 virus, wheras the more avid antibody population reacted both with the homologous and the related cross-reactive A/England/42/72 (H3N2) strains. Sequential elution under acid conditions did not completely remove the bound anti-haemagglutinin antibodies and those eluted retained little of their anti-haemagglutinin activity. From a practical point of view, given a specific antiserum, it is feasible to use whole virus as an immunoadsorbent for the purpose of isolating populations of antibodies of different avidities and cross-reactivities. Furthermore, sodium iodide as an eluting agent has proved most effective in recovery of active  and stable antibodies from the agarosebound virus.", "contents": "Isolation of anti-haemagglutinin antibodies with an influenza A virus immunoadsorbent. The X-31 strain of influenza A (H3N2) virus has been covalently bound to CNBr activated agarose for the separation of anti-haemagglutinin antibodies. The virus immunoadsorbent was used repeatedly under high ionic strength alkali buffer and acid conditions without altering appreciably its antibody binding capacity. Sequential elution of bound anti-haemagglutinin antibodies with increasing concentrations of sodium iodide has enabled the physical separation of antibody populations with low and high avidity for the virus immunoadsorbent. In haemagglutination inhibition (h1) assays, the less avid population reacted only with the homologous X-31 virus, wheras the more avid antibody population reacted both with the homologous and the related cross-reactive A/England/42/72 (H3N2) strains. Sequential elution under acid conditions did not completely remove the bound anti-haemagglutinin antibodies and those eluted retained little of their anti-haemagglutinin activity. From a practical point of view, given a specific antiserum, it is feasible to use whole virus as an immunoadsorbent for the purpose of isolating populations of antibodies of different avidities and cross-reactivities. Furthermore, sodium iodide as an eluting agent has proved most effective in recovery of active  and stable antibodies from the agarosebound virus."}
{"id": "PMID:13127", "title": "The use of early embryo aggregation derived chimaeras. I. To study immunological tolerance.", "content": "Early embryo aggregation mouse chimaeras have proven an invaluable tool to study mechanisms involved in tolerance. Such chimaeras are most commonly derived following the aggregation of two undifferentiated embryos and therefore not suprisingly they were originally considered examples of classic immunological tolerance. Since this time alternative mechanisms including humoral and cell suppressor activity have been suggested and until recently tolerance in tetraparental chimaeras has remained a controversy. This controversy is now reviewed in the light of recent findings which has suggested that such mice are in fact examples of classic tolerance with the possibility that this is achieved by heterogenous elimination of the clones of potentially self in equilibrium self auto-reactive cells.", "contents": "The use of early embryo aggregation derived chimaeras. I. To study immunological tolerance. Early embryo aggregation mouse chimaeras have proven an invaluable tool to study mechanisms involved in tolerance. Such chimaeras are most commonly derived following the aggregation of two undifferentiated embryos and therefore not suprisingly they were originally considered examples of classic immunological tolerance. Since this time alternative mechanisms including humoral and cell suppressor activity have been suggested and until recently tolerance in tetraparental chimaeras has remained a controversy. This controversy is now reviewed in the light of recent findings which has suggested that such mice are in fact examples of classic tolerance with the possibility that this is achieved by heterogenous elimination of the clones of potentially self in equilibrium self auto-reactive cells."}
{"id": "PMID:13129", "title": "Effects of prolonged continuous exposure of human skin to water: a reassessment.", "content": "Continuous exposure of human skin to water in small plastic cups for periods of 72 and 144 hr produced a mild, transient dermatitis in half the sites tested. The degree of dermatitis was only slightly greater at 144 than at 72 hr, and was unrelated to the pH of the water samples. Comparison of soap-pretreated to non-pretreated skin areas showed a significant tendency for the more severe dermatitis to be present on the non-pretreated skin areas at higher pH's. There was virtually no coating of hairs with waxy yellowish material (clumps of bacteria), and no lesion was produced that resembled warm-water-immersion injuries.", "contents": "Effects of prolonged continuous exposure of human skin to water: a reassessment. Continuous exposure of human skin to water in small plastic cups for periods of 72 and 144 hr produced a mild, transient dermatitis in half the sites tested. The degree of dermatitis was only slightly greater at 144 than at 72 hr, and was unrelated to the pH of the water samples. Comparison of soap-pretreated to non-pretreated skin areas showed a significant tendency for the more severe dermatitis to be present on the non-pretreated skin areas at higher pH's. There was virtually no coating of hairs with waxy yellowish material (clumps of bacteria), and no lesion was produced that resembled warm-water-immersion injuries."}
{"id": "PMID:13131", "title": "Simple assay for glycerophospholipid hydrolase activity of postheparin plasma.", "content": "An assay using radioactive substrates is described that permits rapid determinations of glycerophospholipid-hydrolyzing activity in postheparin plasma or its fractions. Optimal conditions are described for hydrolysis of phosphatidylcholine and phosphatidylethanolamine. A minimum of only 2 mul of normal postheparin plasma is used and no extraction of the reaction products is required before their separation by thin-layer chromatography. We found that after an optimal heparin dose of 60 units/kg body weight the rate of hydrolysis for diacyl glycerophosphocholine and diacyl glycerophosphoethanolamine is 1.16 mumoles/ml per hr and 22.4 mumoles/ml per hr, respectively.", "contents": "Simple assay for glycerophospholipid hydrolase activity of postheparin plasma. An assay using radioactive substrates is described that permits rapid determinations of glycerophospholipid-hydrolyzing activity in postheparin plasma or its fractions. Optimal conditions are described for hydrolysis of phosphatidylcholine and phosphatidylethanolamine. A minimum of only 2 mul of normal postheparin plasma is used and no extraction of the reaction products is required before their separation by thin-layer chromatography. We found that after an optimal heparin dose of 60 units/kg body weight the rate of hydrolysis for diacyl glycerophosphocholine and diacyl glycerophosphoethanolamine is 1.16 mumoles/ml per hr and 22.4 mumoles/ml per hr, respectively."}
{"id": "PMID:13132", "title": "Assay for the terminal enzyme of the stearoyl coenzyme A desaturase system using chick embryo liver microsomes.", "content": "The NADH-dependent stearoyl CoA desaturase of hepatic microsomes (EC 1.14.99.5) is an enzyme system consisting of cytochrome b5 reductase (EC 1.6.2.2), cytochrome b5, and the terminal desaturase. We have developed a simple method for routine assay of the terminal enzyme based on complementation of the enzyme with chick embryo liver microsomes lacking desaturase activity. Desaturation of [1-14C]stearoyl CoA by the enzyme-microsome mixture is then assayed by thin-layer chromatography of the reaction products and determination of the amount of oleate formed. Microsomes from the livers of starved-refed rats were used as the source of the stearoyl CoA desaturase. The enzyme alone, solubilized and free from cytocrome b5 reductase and cytochrome b5, was unable to catalyze the desaturation of stearoyl CoA. However, after preincubation with chick embryo liver microsomes in the presence of 1% Triton X-100, the enzyme was active. The enzyme activity was linear with time and desaturase protein under the conditions described and depended on the concentrations of Triton X-100 present in the preincubation and the assay. The optimum concentrations of Triton X-100 were 1% for the preincubation and 0.1-0.15% in the assay. The desaturation activity was dependent on NADH and O2, and was inhibited 95% by 1 mM KCN. The use of chick embryo liver microsomes in this method eliminates the need to use purified cytochrome b5 reductase, cytochrome b5, and liposomes for routine assays and greatly reduces the complexities of timing and order of addition encountered in the existing assays.", "contents": "Assay for the terminal enzyme of the stearoyl coenzyme A desaturase system using chick embryo liver microsomes. The NADH-dependent stearoyl CoA desaturase of hepatic microsomes (EC 1.14.99.5) is an enzyme system consisting of cytochrome b5 reductase (EC 1.6.2.2), cytochrome b5, and the terminal desaturase. We have developed a simple method for routine assay of the terminal enzyme based on complementation of the enzyme with chick embryo liver microsomes lacking desaturase activity. Desaturation of [1-14C]stearoyl CoA by the enzyme-microsome mixture is then assayed by thin-layer chromatography of the reaction products and determination of the amount of oleate formed. Microsomes from the livers of starved-refed rats were used as the source of the stearoyl CoA desaturase. The enzyme alone, solubilized and free from cytocrome b5 reductase and cytochrome b5, was unable to catalyze the desaturation of stearoyl CoA. However, after preincubation with chick embryo liver microsomes in the presence of 1% Triton X-100, the enzyme was active. The enzyme activity was linear with time and desaturase protein under the conditions described and depended on the concentrations of Triton X-100 present in the preincubation and the assay. The optimum concentrations of Triton X-100 were 1% for the preincubation and 0.1-0.15% in the assay. The desaturation activity was dependent on NADH and O2, and was inhibited 95% by 1 mM KCN. The use of chick embryo liver microsomes in this method eliminates the need to use purified cytochrome b5 reductase, cytochrome b5, and liposomes for routine assays and greatly reduces the complexities of timing and order of addition encountered in the existing assays."}
{"id": "PMID:13133", "title": "Alterations of prostaglandin E2-9-ketoreductase activity in proliferating skin.", "content": "The activity of an NADPH-dependent PGE2-9-ketoreductase has been demonstrated in rat and human skin. This activity is localized in the high speed supernatant fraction, indicating the presence of an active PGE2-9-ketoreductase associated with the cytoplasmic fraction of the skin. Transformation of PGE2 into PGF2alpha is enhanced by skin specimens from psoriatic plaques and EFA-deficient rats, both characterized by excessive cellular proliferation and increased NADPH production. Incubations of the 105,000 g supernatant fractions from normal and EFA-deficient rats demonstrated that the activity of the PGE2-9-ketoreductase was elevated in high speed preparations from EFA-deficient rats. Results from these studies suggest that the increased activity of PGE2-9-ketoreductase observed in skin from human psoriatic plaques and EFA-deficient rats may be due in part to the increased generation of NADPH by these tissues and in part to alteration of the PGE2-9-ketoreductase by the excessive proliferation of the tissues.", "contents": "Alterations of prostaglandin E2-9-ketoreductase activity in proliferating skin. The activity of an NADPH-dependent PGE2-9-ketoreductase has been demonstrated in rat and human skin. This activity is localized in the high speed supernatant fraction, indicating the presence of an active PGE2-9-ketoreductase associated with the cytoplasmic fraction of the skin. Transformation of PGE2 into PGF2alpha is enhanced by skin specimens from psoriatic plaques and EFA-deficient rats, both characterized by excessive cellular proliferation and increased NADPH production. Incubations of the 105,000 g supernatant fractions from normal and EFA-deficient rats demonstrated that the activity of the PGE2-9-ketoreductase was elevated in high speed preparations from EFA-deficient rats. Results from these studies suggest that the increased activity of PGE2-9-ketoreductase observed in skin from human psoriatic plaques and EFA-deficient rats may be due in part to the increased generation of NADPH by these tissues and in part to alteration of the PGE2-9-ketoreductase by the excessive proliferation of the tissues."}
{"id": "PMID:13134", "title": "Cholic acid biosynthesis: conversion of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into 5beta-cholestane-3alpha,7alpha, 12alpha,24beta,25-pentol by human and rat liver microsomes.", "content": "This paper describes the conversion of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol by liver microsomes. A sensitive radioactive assay for measuring the formation of 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol was developed. Optimal assay conditions for human and rat microsomal systems were established. A higher 24beta-hydroxylation activity was detected in rat than in human liver under the conditions employed. The hydroxylation of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol by the rat liver microsomal fraction fortified with NADPH was stimulated about two-fold by administration of phenobarbital. Phenobarbital treatment also stimulated hydroxylations at C-23, C-24alpha, and C-26. Carbon monoxide markedly inhibited all side-chain hydroxylations. In contrast, side-chain hydroxylase activities were not affected in animals deprived of food for 48 hr. These results are consistent with a previously postulated cholic acid biosynthetic pathway involving 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol as a key intermediate in man and in the rat.", "contents": "Cholic acid biosynthesis: conversion of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into 5beta-cholestane-3alpha,7alpha, 12alpha,24beta,25-pentol by human and rat liver microsomes. This paper describes the conversion of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol by liver microsomes. A sensitive radioactive assay for measuring the formation of 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol was developed. Optimal assay conditions for human and rat microsomal systems were established. A higher 24beta-hydroxylation activity was detected in rat than in human liver under the conditions employed. The hydroxylation of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol by the rat liver microsomal fraction fortified with NADPH was stimulated about two-fold by administration of phenobarbital. Phenobarbital treatment also stimulated hydroxylations at C-23, C-24alpha, and C-26. Carbon monoxide markedly inhibited all side-chain hydroxylations. In contrast, side-chain hydroxylase activities were not affected in animals deprived of food for 48 hr. These results are consistent with a previously postulated cholic acid biosynthetic pathway involving 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol as a key intermediate in man and in the rat."}
{"id": "PMID:13135", "title": "Analysis of rat serum apolipoproteins by isoelectric focusing. II. Studies on the low molecular weight subunits.", "content": "The low molecular weight proteins of rat apo HDL and apo VLDL have been isolated and analyzed by the technique of isoelectric focusing. Sephadex fractions from apo HDL (HS-3) and apo VLDL (VS-3) that contain these proteins reveal three major bands with apparent isoelectric points of pH 4.50, 4.67, and 4.74, as well as three minor bands at pH 4.43, 4.57, and 4.61. In addition, apo HDL has a major band at pI of 4.83. DEAE-Cellulose chromatography was used to prepare purified fractions of these components that were characterized by N-terminal analyses and molecular weight determinantions by SDS gel electrophoresis. The major low molecular weight components of apo HDL were focused on a slab gel and the bands were identified as A-II (pI 4.83), C-II (pI 4.74), C-III-0 (pI 4.67), and C-III-3 (pI 4.50). Neuraminidase treatment of apo HDL, followed by isoelectric focusing, suggested that the other bands, which have not previously been reported, may be additional forms of the C-III protein, differing only in their content of sialic acid.", "contents": "Analysis of rat serum apolipoproteins by isoelectric focusing. II. Studies on the low molecular weight subunits. The low molecular weight proteins of rat apo HDL and apo VLDL have been isolated and analyzed by the technique of isoelectric focusing. Sephadex fractions from apo HDL (HS-3) and apo VLDL (VS-3) that contain these proteins reveal three major bands with apparent isoelectric points of pH 4.50, 4.67, and 4.74, as well as three minor bands at pH 4.43, 4.57, and 4.61. In addition, apo HDL has a major band at pI of 4.83. DEAE-Cellulose chromatography was used to prepare purified fractions of these components that were characterized by N-terminal analyses and molecular weight determinantions by SDS gel electrophoresis. The major low molecular weight components of apo HDL were focused on a slab gel and the bands were identified as A-II (pI 4.83), C-II (pI 4.74), C-III-0 (pI 4.67), and C-III-3 (pI 4.50). Neuraminidase treatment of apo HDL, followed by isoelectric focusing, suggested that the other bands, which have not previously been reported, may be additional forms of the C-III protein, differing only in their content of sialic acid."}
{"id": "PMID:13136", "title": "Lathyritic activity of isoniazid.", "content": "Although isoniazid is mainly known and used for its antituberculous properties, it is also a lathyrogenic agent. This paper presents data confirming the lathyritic activity of isoniazid in vitro and in vivo and suggests that its action on connective tissue may be partly responsible for its therapeutic effectiveness.", "contents": "Lathyritic activity of isoniazid. Although isoniazid is mainly known and used for its antituberculous properties, it is also a lathyrogenic agent. This paper presents data confirming the lathyritic activity of isoniazid in vitro and in vivo and suggests that its action on connective tissue may be partly responsible for its therapeutic effectiveness."}
{"id": "PMID:13137", "title": "Human placental alcohol dehydrogenase.", "content": "Alcohol dehydrogenase derived from the term human placenta was investigated in the 104,000xg supernatant fraction. Kinetic experiments yielded an average Vmax of 6.1 units, a Km of  5X10(-3)M and optimum activity at pH 10.0. Electrophoresis at pH 9.6 in glycine buffer showed four bands, however only two bands were observed at pH 8.6. Properties of this placental enzyme may be unique and its participation in the overall metabolic function of this tissue is unclear.", "contents": "Human placental alcohol dehydrogenase. Alcohol dehydrogenase derived from the term human placenta was investigated in the 104,000xg supernatant fraction. Kinetic experiments yielded an average Vmax of 6.1 units, a Km of  5X10(-3)M and optimum activity at pH 10.0. Electrophoresis at pH 9.6 in glycine buffer showed four bands, however only two bands were observed at pH 8.6. Properties of this placental enzyme may be unique and its participation in the overall metabolic function of this tissue is unclear."}
{"id": "PMID:13138", "title": "[Excretion of erythropoietin by humans during the production of alkaline or acidic urine (author's transl)].", "content": "Marver & Gurney ((1968)Ann.N.Y.Acad.Sci. 149, 570-575) reported that the erythropoietin excretion in two anaemic patients increased 17 and 3.5-fold, respectively, during the production of alkaline urine by the administration of NaHCO3. We have studied the excretion of erythropoietin in 6 persons, following the daily administration of 3.5 g of NH4Cl, which resulted in an average urine pH of 5.9; and following the administration of hexapotassium hexasodium pentacitrate, which increased the urine pH TO 7.5. In the alkaline urine, erythropoietin excretion showed an average, but non-significant, two-fold increase. The increase was significant in only two experimental persons.", "contents": "[Excretion of erythropoietin by humans during the production of alkaline or acidic urine (author's transl)]. Marver & Gurney ((1968)Ann.N.Y.Acad.Sci. 149, 570-575) reported that the erythropoietin excretion in two anaemic patients increased 17 and 3.5-fold, respectively, during the production of alkaline urine by the administration of NaHCO3. We have studied the excretion of erythropoietin in 6 persons, following the daily administration of 3.5 g of NH4Cl, which resulted in an average urine pH of 5.9; and following the administration of hexapotassium hexasodium pentacitrate, which increased the urine pH TO 7.5. In the alkaline urine, erythropoietin excretion showed an average, but non-significant, two-fold increase. The increase was significant in only two experimental persons."}
{"id": "PMID:13139", "title": "[Activation of acid prostate phosphatase by 1-pentanol (author's transl)].", "content": "The activity of the acid phosphatase from prostate was increased by 90% by the addition of 150 mmol/l 1-pentanol to the assay mixture. This activation results in an increased turnover of substrate, so that the phosphomonoester is cleaved more rapidly and a correspondingly larger amount of the release organic residue can be detected. The quantity of free phosphate, however, does not correspond to the substrate turnover, because some of the phosphate residue is transferred from the substrate to the 1-pentanol in a transphosphorylation reaction. The influence of the substrate, buffer, pH and of tartrate on the 1-pentanol-activated prostate phosphatase was investigated.", "contents": "[Activation of acid prostate phosphatase by 1-pentanol (author's transl)]. The activity of the acid phosphatase from prostate was increased by 90% by the addition of 150 mmol/l 1-pentanol to the assay mixture. This activation results in an increased turnover of substrate, so that the phosphomonoester is cleaved more rapidly and a correspondingly larger amount of the release organic residue can be detected. The quantity of free phosphate, however, does not correspond to the substrate turnover, because some of the phosphate residue is transferred from the substrate to the 1-pentanol in a transphosphorylation reaction. The influence of the substrate, buffer, pH and of tartrate on the 1-pentanol-activated prostate phosphatase was investigated."}
{"id": "PMID:13140", "title": "[The electrophoretic pattern of gamma-glutamyl transferase in serum and its alteration by chylomicrons (author's transl)].", "content": "Using the sera from 20 patients with elevated gamma-glutamyl transferase activity (EC 2.3.2.2) due to intra- or posthepatic cholestasis, the enzyme was separated into four bands by cellulose acetate foil electrophoresis. The gamma-glutamyl transferase pattern permitted no differentiation between intra- or posthepatic cholestasis. Protein and lipid electrophoresis was performed simultaneously for each serum. It was found that a gamma-glutamyl transferase band, which appeared at the origin in 11 sera, was only observed in lipaemic sera containing chylomicrons. This band of gamma-glutamyl transferase does not, however, represent a true isoenzyme, because it results from a complex between chylomicrons and gamma-glutamyl transferase, which is separated with the chylomicrons, or is produced by the mixing of sera.", "contents": "[The electrophoretic pattern of gamma-glutamyl transferase in serum and its alteration by chylomicrons (author's transl)]. Using the sera from 20 patients with elevated gamma-glutamyl transferase activity (EC 2.3.2.2) due to intra- or posthepatic cholestasis, the enzyme was separated into four bands by cellulose acetate foil electrophoresis. The gamma-glutamyl transferase pattern permitted no differentiation between intra- or posthepatic cholestasis. Protein and lipid electrophoresis was performed simultaneously for each serum. It was found that a gamma-glutamyl transferase band, which appeared at the origin in 11 sera, was only observed in lipaemic sera containing chylomicrons. This band of gamma-glutamyl transferase does not, however, represent a true isoenzyme, because it results from a complex between chylomicrons and gamma-glutamyl transferase, which is separated with the chylomicrons, or is produced by the mixing of sera."}
{"id": "PMID:13142", "title": "Rhodanese from Thiobacillus A2: catalysis of reactions of thiosulphate with dihydrolipoate and dihydrolipoamide.", "content": "Rhodanese (thiosulphate:cyanide sulphurtransferase EC.2.8.1.1) was purified 25- to 30-fold from thiosulphate-grown Thiobacillus A2. It exhibited a pH optimum between pH 10-2 and 10-4 and apparent Km values of 0-36 mM-Na2S2O3 and 17 mM-KCN. Ultraviolet spectrophotometry and thin-layer chromatography showed that the enzyme catalysed the reaction of S2O3(2-) with dihydrolipoic acid or dihydrolipoamide, producing alpha-lipoate or lipoamide, with the intermediate production of the persulphides of dihydrolipoate and dihydrolipoamide, which were demonstrated chromatographically. This is the first demonstration of catalysis by a thiobacillus rhodanese of reactions which are likely to be physiologically important in the oxidative dissimilation of thiosulphate by a central energy-conserving pathway.", "contents": "Rhodanese from Thiobacillus A2: catalysis of reactions of thiosulphate with dihydrolipoate and dihydrolipoamide. Rhodanese (thiosulphate:cyanide sulphurtransferase EC.2.8.1.1) was purified 25- to 30-fold from thiosulphate-grown Thiobacillus A2. It exhibited a pH optimum between pH 10-2 and 10-4 and apparent Km values of 0-36 mM-Na2S2O3 and 17 mM-KCN. Ultraviolet spectrophotometry and thin-layer chromatography showed that the enzyme catalysed the reaction of S2O3(2-) with dihydrolipoic acid or dihydrolipoamide, producing alpha-lipoate or lipoamide, with the intermediate production of the persulphides of dihydrolipoate and dihydrolipoamide, which were demonstrated chromatographically. This is the first demonstration of catalysis by a thiobacillus rhodanese of reactions which are likely to be physiologically important in the oxidative dissimilation of thiosulphate by a central energy-conserving pathway."}
{"id": "PMID:13144", "title": "An alginate lysate from Azotobacter vinelandii phage.", "content": "The alginate depolymerase associated with bacteriophage infection of Azotobacter vinelandii has been used in the analysis of sodium alginate. The enzyme degraded the polysaccharide to a series of oligouronides each containing a terminal 4-deoxy-alpha-L-erythro-hex-4-enopyranuronosyl residue. Analysis of these oligouronides, together with kinetic information, indicated that the enzyme was specific for mannuronic acid-containing regions of the polyuronide. The specificity of the enzyme made it possible to determine the primary structure of the macro-molecule. The phage-induced enzyme was shown to be distinct from the alginate lyase elaborated by the host organisms by its pH optimum, molecular weight, Michaelis constant and stability.", "contents": "An alginate lysate from Azotobacter vinelandii phage. The alginate depolymerase associated with bacteriophage infection of Azotobacter vinelandii has been used in the analysis of sodium alginate. The enzyme degraded the polysaccharide to a series of oligouronides each containing a terminal 4-deoxy-alpha-L-erythro-hex-4-enopyranuronosyl residue. Analysis of these oligouronides, together with kinetic information, indicated that the enzyme was specific for mannuronic acid-containing regions of the polyuronide. The specificity of the enzyme made it possible to determine the primary structure of the macro-molecule. The phage-induced enzyme was shown to be distinct from the alginate lyase elaborated by the host organisms by its pH optimum, molecular weight, Michaelis constant and stability."}
{"id": "PMID:13143", "title": "Regulation of the tricarboxylic acid cycle and poly-beta-hydroxybutyrate metabolism in Azotobacter beijerinckii grown under nitrogen or oxygen limitation.", "content": "Azotobacter beijerinckii was grown in ammonia-free glucose/mineral salts media in chemostat culture under oxygen or nitrogen limitation. Selected enzymes of the tricarboxylic acid cycle and poly-beta-hydroxybutyrate metabolism were monitored in relation to oxygen supply for both steady and transition states. Two dissolved oxygen concentrations were used for the nitrogen-limited steady state to investigate the possible effects of respiratory protection of nitrogenase on these enzymes. The levels of NADH oxidase, isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase increased markedly on relaxation of oxygen limitation while pyruvate dehydrogenase and citrate synthase were relatively unaffected. beta-Ketothiolase and acetoacetyl-CoA reductase levels decreased as oxygen limitation was relaxed. Respiratory activity, as measured by the QO2 value, increased with oxygen supply rate. Imposition of oxygen limitation on a nitrogen-limited culture caused an immediate increase in the NADH/NAD ratio but this rapidly readjusted to its previous steady-state value. These changes are discussed in relation to respiratory protection of nitrogenase and poly-beta-hydroxybutyrate metabolism in A. beijerinckii.", "contents": "Regulation of the tricarboxylic acid cycle and poly-beta-hydroxybutyrate metabolism in Azotobacter beijerinckii grown under nitrogen or oxygen limitation. Azotobacter beijerinckii was grown in ammonia-free glucose/mineral salts media in chemostat culture under oxygen or nitrogen limitation. Selected enzymes of the tricarboxylic acid cycle and poly-beta-hydroxybutyrate metabolism were monitored in relation to oxygen supply for both steady and transition states. Two dissolved oxygen concentrations were used for the nitrogen-limited steady state to investigate the possible effects of respiratory protection of nitrogenase on these enzymes. The levels of NADH oxidase, isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase increased markedly on relaxation of oxygen limitation while pyruvate dehydrogenase and citrate synthase were relatively unaffected. beta-Ketothiolase and acetoacetyl-CoA reductase levels decreased as oxygen limitation was relaxed. Respiratory activity, as measured by the QO2 value, increased with oxygen supply rate. Imposition of oxygen limitation on a nitrogen-limited culture caused an immediate increase in the NADH/NAD ratio but this rapidly readjusted to its previous steady-state value. These changes are discussed in relation to respiratory protection of nitrogenase and poly-beta-hydroxybutyrate metabolism in A. beijerinckii."}
{"id": "PMID:13147", "title": "Growth of Spirillum lipoferum at constant partial pressures of oxygen, and the properties of its nitrogenase in cell-free extracts.", "content": "Spirillum lipoferum, an N2-fixing organism, was grown at constant concentrations of dissolved O2. When supplied with NH4+ aerobically, its doubling time was 1 h; when it fixed N2 microaerophilically, its doubling time was 5-5 to 7 h and the optimal PO2 for growth was 0-005 to 0-007 atm. At its optimal PO2 for growth on N2, S. lipoferum assimilated 8 to 10 mg nitrogen/g carbon substrate used; its efficiency was less at higher PO2 levels. Nitrogenase in cell-free extracts required Mg2+ and Mn2+, and the Fe-protein was activated by Rhodospirillum rubrum activating factor. The nitrogenase had an optimal pH of 7-1 to 7-4 and an apparent Km for acetylene of 0-0036 atm. Extracts of S. lipoferum lost their nitrogenase activity on storage at -18 degrees C, and activity was restored by adding purified Fe-protein from other N2-fixing bacteria.", "contents": "Growth of Spirillum lipoferum at constant partial pressures of oxygen, and the properties of its nitrogenase in cell-free extracts. Spirillum lipoferum, an N2-fixing organism, was grown at constant concentrations of dissolved O2. When supplied with NH4+ aerobically, its doubling time was 1 h; when it fixed N2 microaerophilically, its doubling time was 5-5 to 7 h and the optimal PO2 for growth was 0-005 to 0-007 atm. At its optimal PO2 for growth on N2, S. lipoferum assimilated 8 to 10 mg nitrogen/g carbon substrate used; its efficiency was less at higher PO2 levels. Nitrogenase in cell-free extracts required Mg2+ and Mn2+, and the Fe-protein was activated by Rhodospirillum rubrum activating factor. The nitrogenase had an optimal pH of 7-1 to 7-4 and an apparent Km for acetylene of 0-0036 atm. Extracts of S. lipoferum lost their nitrogenase activity on storage at -18 degrees C, and activity was restored by adding purified Fe-protein from other N2-fixing bacteria."}
{"id": "PMID:13148", "title": "Adenylate energy charge during batch culture of Beneckea natriegens.", "content": "The value of the adenylate energy charge, i.e. ([ATP] + 1/2[ADP])/([ATP] + [ADP] + [AMP]), during batch culture of Beneckea natriegens remained relatively constant during the exponential and early stationary phases of the growth cycle. During exponential growth the intracellular ATP content remained constant, the amount of ATP in the culture increasing proportionally with growth; these conditions were unaltered during growth in the presence of added cyclic AMP. On cessation of growth, significant variation in bacterial ATP content was observed depending on whether growth of the cultures terminated due to exhaustion of carbon or nitrogen from the medium, and on the presence or absence of added cyclic AMP.", "contents": "Adenylate energy charge during batch culture of Beneckea natriegens. The value of the adenylate energy charge, i.e. ([ATP] + 1/2[ADP])/([ATP] + [ADP] + [AMP]), during batch culture of Beneckea natriegens remained relatively constant during the exponential and early stationary phases of the growth cycle. During exponential growth the intracellular ATP content remained constant, the amount of ATP in the culture increasing proportionally with growth; these conditions were unaltered during growth in the presence of added cyclic AMP. On cessation of growth, significant variation in bacterial ATP content was observed depending on whether growth of the cultures terminated due to exhaustion of carbon or nitrogen from the medium, and on the presence or absence of added cyclic AMP."}
{"id": "PMID:13149", "title": "Agoraphobia: indications for the application of the multimodal behavioral conceptualization.", "content": "Agoraphobia, characterized as fear of going into public places, vehicles, shops, streets, and so forth, is a prevalent syndrome which permeates the patient's life. The efficacy of psychoanalytic, behavioral, and pharmacological treatments has been disappointing. The pervasive nature of agoraphobia dictates that its treatment is most efficacious when a combination of separate although interactive techniques is applied in concert. A multimodal behavioral conceptualization provides the vehicle for the systematic combined application of seemingly diverse individual approaches through monitoring and treating the BASIC ID, an acronym for behavior, affect, sensation, imagery, cognition, interpersonal relationships, and drugs. In an illustrative case, application of the multimodal behavioral conceptualization was instrumental in bringing relief to an agoraphobic patient's distress and disabilities.", "contents": "Agoraphobia: indications for the application of the multimodal behavioral conceptualization. Agoraphobia, characterized as fear of going into public places, vehicles, shops, streets, and so forth, is a prevalent syndrome which permeates the patient's life. The efficacy of psychoanalytic, behavioral, and pharmacological treatments has been disappointing. The pervasive nature of agoraphobia dictates that its treatment is most efficacious when a combination of separate although interactive techniques is applied in concert. A multimodal behavioral conceptualization provides the vehicle for the systematic combined application of seemingly diverse individual approaches through monitoring and treating the BASIC ID, an acronym for behavior, affect, sensation, imagery, cognition, interpersonal relationships, and drugs. In an illustrative case, application of the multimodal behavioral conceptualization was instrumental in bringing relief to an agoraphobic patient's distress and disabilities."}
{"id": "PMID:13160", "title": "Homosynaptic depression and transmitter turnover in spinal monosynaptic pathway.", "content": "1. The transmission in the spinal monosynaptic pathway was studied during repetitive stimulation of a motor nerve by 10 stimuli at 2, 5, or 10 Hz in spinal cats. Initially, the amplitudes of the monosynaptic responses rapidly declined, reaching a plateau after a few stimuli. The level of the plateau was inversely related to the frequency of stimulation. 2. This depression of monosynaptic response was seen only when the same pathway was stimulated; the response elicited from the lateral gastrocnemius was not depressed when preceded by stimulation of the medial gastrocnemius nerve and vice versa. Pretreatment with semicarbazide left the homosynaptic depression unchanged while suppressing the dorsal root reflex. The participation of a depolarization of primary afferents in the described depression is, therefore, unlikely. 3. The decrease of transmitter release by successive volleys, which is the cause of the observed depression, could conceivably be related to the depletion of transmitter stores. 4. A procedure is described, based on this assumption, which allows the calculation of transmitter turnover. The input-output relation in the spinal monosynaptic pathway is used to convert the amplitudes of monosynaptic responses to the amounts of transmitter, both relative to the maximum response. The changes of transmitter release are analyzed under the assumption that each volley releases instantaneously a constant fraction of the transmitter store available for release and that this store is replenished at a constant fraction of the depleted part per second. 5. The values of fractional release per volley were about 0.4, irrespective of frequency of stimulation. 6. The values of fractional replenishment per second ranged from about 1 to 5 on the average, depending directly on the frequency of stimulation. 7. It is suggested that the described procedure might be useful in analyzing drug effects on synaptic transmission.", "contents": "Homosynaptic depression and transmitter turnover in spinal monosynaptic pathway. 1. The transmission in the spinal monosynaptic pathway was studied during repetitive stimulation of a motor nerve by 10 stimuli at 2, 5, or 10 Hz in spinal cats. Initially, the amplitudes of the monosynaptic responses rapidly declined, reaching a plateau after a few stimuli. The level of the plateau was inversely related to the frequency of stimulation. 2. This depression of monosynaptic response was seen only when the same pathway was stimulated; the response elicited from the lateral gastrocnemius was not depressed when preceded by stimulation of the medial gastrocnemius nerve and vice versa. Pretreatment with semicarbazide left the homosynaptic depression unchanged while suppressing the dorsal root reflex. The participation of a depolarization of primary afferents in the described depression is, therefore, unlikely. 3. The decrease of transmitter release by successive volleys, which is the cause of the observed depression, could conceivably be related to the depletion of transmitter stores. 4. A procedure is described, based on this assumption, which allows the calculation of transmitter turnover. The input-output relation in the spinal monosynaptic pathway is used to convert the amplitudes of monosynaptic responses to the amounts of transmitter, both relative to the maximum response. The changes of transmitter release are analyzed under the assumption that each volley releases instantaneously a constant fraction of the transmitter store available for release and that this store is replenished at a constant fraction of the depleted part per second. 5. The values of fractional release per volley were about 0.4, irrespective of frequency of stimulation. 6. The values of fractional replenishment per second ranged from about 1 to 5 on the average, depending directly on the frequency of stimulation. 7. It is suggested that the described procedure might be useful in analyzing drug effects on synaptic transmission."}
{"id": "PMID:13161", "title": "A quantitative study of leukocyte cohesion: effects of divalent cations and pH.", "content": "Leukocyte cell-to-cell adhesion was studied with a cell monolayer technique. The amount of protein retained on the coverslip reflected the number of adhering cells. When polymorphonuclear leukocytes were suspended in a balanced salt solution at neutral pH containing no bivalent cations, they adhered to the glass surface but not to each other. Magnesium or calcium at concentrations above 1 mM caused cell-to-cell adhesion. Stannous and chromate ions had no effect on leukocyte cell-to-cell adhesion. Acid pH also induced leukocyte aggregation. This last effect could be reversed by washing the cells with a balanced salt solution at neutral pH, but it could not be reversed by alcohol.", "contents": "A quantitative study of leukocyte cohesion: effects of divalent cations and pH. Leukocyte cell-to-cell adhesion was studied with a cell monolayer technique. The amount of protein retained on the coverslip reflected the number of adhering cells. When polymorphonuclear leukocytes were suspended in a balanced salt solution at neutral pH containing no bivalent cations, they adhered to the glass surface but not to each other. Magnesium or calcium at concentrations above 1 mM caused cell-to-cell adhesion. Stannous and chromate ions had no effect on leukocyte cell-to-cell adhesion. Acid pH also induced leukocyte aggregation. This last effect could be reversed by washing the cells with a balanced salt solution at neutral pH, but it could not be reversed by alcohol."}
{"id": "PMID:13163", "title": "Contract systems and grading policies.", "content": "The contract system can be a motivating factor to student learning. Caution is necessary to ensure the students who are graduating from the program have the knowledge base to pass the SBTPE. The faculty of one program believe their contract system which has evolved from five years of experience meets these criteria. Furthermore, patient care ultimately benefits. The nursing student exposed to an educational system in which his individual worth is recognized and learning needs met can respect the patient's rights and his individual health needs.", "contents": "Contract systems and grading policies. The contract system can be a motivating factor to student learning. Caution is necessary to ensure the students who are graduating from the program have the knowledge base to pass the SBTPE. The faculty of one program believe their contract system which has evolved from five years of experience meets these criteria. Furthermore, patient care ultimately benefits. The nursing student exposed to an educational system in which his individual worth is recognized and learning needs met can respect the patient's rights and his individual health needs."}
{"id": "PMID:13159", "title": "Cyanide intoxication in Macaca mulatta. Physiological and neuropathological aspects.", "content": "Sodium cyanide was infused intravenously in 11 lightly anaesthetised and spontaneously breathing M. mulatta. In most, the EEG, ECG, respiratory rate, blood pressure, cerebral venous sinus pressure, end-tidal pCO2 and body temperature were recorded. Blood gases, pH, lactate and pyruvate were estimated in arterial and venous sinus blood samples. There was an initial hyperventilation with tetany in all animals. A rapid rate of cyanide infusion led to apnoea. An isoelectric or near-isoelectric EEG was usually precipitated by bradycardia often with additional hypotension. Neither epileptic seizures nor their EEG concomitants were seen at any stage. Three animals died of early heart failure. Brain damage was seen in 4 animals surviving up to 98 hr. White matter was involved in all. Ischaemic neuronal alterations, restricted to the striatum of one animal, were attributed to major circulatory complications. It was concluded that under these experimental conditions there is no evidence for hypoxic neuronal damage of purely histotoxic type.", "contents": "Cyanide intoxication in Macaca mulatta. Physiological and neuropathological aspects. Sodium cyanide was infused intravenously in 11 lightly anaesthetised and spontaneously breathing M. mulatta. In most, the EEG, ECG, respiratory rate, blood pressure, cerebral venous sinus pressure, end-tidal pCO2 and body temperature were recorded. Blood gases, pH, lactate and pyruvate were estimated in arterial and venous sinus blood samples. There was an initial hyperventilation with tetany in all animals. A rapid rate of cyanide infusion led to apnoea. An isoelectric or near-isoelectric EEG was usually precipitated by bradycardia often with additional hypotension. Neither epileptic seizures nor their EEG concomitants were seen at any stage. Three animals died of early heart failure. Brain damage was seen in 4 animals surviving up to 98 hr. White matter was involved in all. Ischaemic neuronal alterations, restricted to the striatum of one animal, were attributed to major circulatory complications. It was concluded that under these experimental conditions there is no evidence for hypoxic neuronal damage of purely histotoxic type."}
{"id": "PMID:13166", "title": "Effect of dietary pH on amino acid utilization and the lysine requirement of fingerling channel catfish.", "content": "The pH of amino acid test diets has been shown to be of major importance in dietary amino acid studies in the channel catfish (Ictalurus punctatus). Maximum growth rate and feed conversion was observed when the test diet was adjusted to pH 7. Growth studies, utilizing a 24% crude protein diet containing an amino acid pattern similar to whole egg protein, indicate that the lysine requirement for fingerling channel catfish is about 1.23% of the diet (dry weight basis) or 5.1% of the dietary protein. The dietary requirement was confirmed by serum free lysine analysis. A marked increase in serum free lysine occurred at a dietary lysine level of approximately 1.2% of the diet.", "contents": "Effect of dietary pH on amino acid utilization and the lysine requirement of fingerling channel catfish. The pH of amino acid test diets has been shown to be of major importance in dietary amino acid studies in the channel catfish (Ictalurus punctatus). Maximum growth rate and feed conversion was observed when the test diet was adjusted to pH 7. Growth studies, utilizing a 24% crude protein diet containing an amino acid pattern similar to whole egg protein, indicate that the lysine requirement for fingerling channel catfish is about 1.23% of the diet (dry weight basis) or 5.1% of the dietary protein. The dietary requirement was confirmed by serum free lysine analysis. A marked increase in serum free lysine occurred at a dietary lysine level of approximately 1.2% of the diet."}
{"id": "PMID:13167", "title": "Rat liver glutathione: possible role as a reservoir of cysteine.", "content": "Rat liver contains a high concentration (7-8mM) of reduced glutathione and its level changes rapidly when starving or feeding rats. We concluded that one of the functions of liver glutathione was to act as a reservoir of cysteine. When starved rats were fed a protein-free diet, the increase in liver glutathione was dependent on the amount of cysteine added to the diet. A cysteine-dependent increase of glutathione was also observed in rats fed a diet containing gelatin with cysteine, but the increase was relatively lowered compared with rats fed a protein-free diet containing the same amount of cysteine. This suppression of the increase in glutathione was observed much more clearly when the gelatin diet was fortified with tryptophan in addition to cysteine. In the presence of tryptophan, L-[35S]-cysteine in the diet appeared to be incorporated primarily into liver and serum proteins, and degradation of liver glutathione must also have been enhanced. Addition of excess cysteine to the diet masked the effects of gelatin and tryptophan, stimulated glutathione synthesis in the liver as well as incorporation of dietary cysteine into protein fractions. Prolonged starvation of rats or injection of dibutyryl-3',5'-cyclic AMP lowered the glutathione level,but the level did not decrease below 2 to 3 mM. These findings suggest that there may be at least two pools of glutathione. A labile fraction, constituting one-third to one-half the total liver glutathione, probably serves as a reservoir of cysteine which can be released by gamma-glutamyl-transferase when necessary.", "contents": "Rat liver glutathione: possible role as a reservoir of cysteine. Rat liver contains a high concentration (7-8mM) of reduced glutathione and its level changes rapidly when starving or feeding rats. We concluded that one of the functions of liver glutathione was to act as a reservoir of cysteine. When starved rats were fed a protein-free diet, the increase in liver glutathione was dependent on the amount of cysteine added to the diet. A cysteine-dependent increase of glutathione was also observed in rats fed a diet containing gelatin with cysteine, but the increase was relatively lowered compared with rats fed a protein-free diet containing the same amount of cysteine. This suppression of the increase in glutathione was observed much more clearly when the gelatin diet was fortified with tryptophan in addition to cysteine. In the presence of tryptophan, L-[35S]-cysteine in the diet appeared to be incorporated primarily into liver and serum proteins, and degradation of liver glutathione must also have been enhanced. Addition of excess cysteine to the diet masked the effects of gelatin and tryptophan, stimulated glutathione synthesis in the liver as well as incorporation of dietary cysteine into protein fractions. Prolonged starvation of rats or injection of dibutyryl-3',5'-cyclic AMP lowered the glutathione level,but the level did not decrease below 2 to 3 mM. These findings suggest that there may be at least two pools of glutathione. A labile fraction, constituting one-third to one-half the total liver glutathione, probably serves as a reservoir of cysteine which can be released by gamma-glutamyl-transferase when necessary."}
{"id": "PMID:13168", "title": "Fatty acid synthesis in testes of fat-deficient and fat-supplemented rats.", "content": "Fatty acid synthesis was studied in testes of rats fed a fat-free or fat-supplemented diet. Testes of fat-deficient rats incorporated nearly twice as much intratesticularly injected [1-14C]acetate into total fatty acids (primarily into palmitic acid) as did supplemented rats. To determine the mechanism for the increased synthesis, the activities of the following enzymes were determined in the cytoplasmic fraction of testicular homogenates: fatty acid synthetase, acetyl CoA carboxylase [EC 6.4.1.2], citrate-cleavage [EC 4.1.3.8], malic [EC 1.1.1.38], and the glucose-l-phosphate dehydrogenase [EC 1.1.1.49]: 6-phosphogluconate dehydrogenase pair [EC 1.1.1.44]. Although the activity of fatty acid synthetase did increase in livers from fat-deficient rats, no change was observed in corresponding testes. No difference between the two groups could be demonstrated in testicular activity of citrate-cleavage enzyme, malic enzyme, or the glucose-6-phosphate dehydrogenase: 6-phosphogluconate dehydrogenase pair. However, the activity of cytoplasmic acetyl CoA carboxylase in testes of rats fed the fat-deficient diet was 1.4 times higher than the activity in testes of rats fed the supplemented diet. Fat deficiency did not affect the specific activity of the testicular microsomal elongation system, assayed by incubation with 14C-malonyl CoA. The concentration of unesterified fatty acids was lower in testes of the fat-deficient compared to supplemented rats, indicating that decreased inhibition of acetyl CoA carboxylase in the fat-deficient rats testes might have been responsible for the observed increased de novo synthesis of palmitic acid.", "contents": "Fatty acid synthesis in testes of fat-deficient and fat-supplemented rats. Fatty acid synthesis was studied in testes of rats fed a fat-free or fat-supplemented diet. Testes of fat-deficient rats incorporated nearly twice as much intratesticularly injected [1-14C]acetate into total fatty acids (primarily into palmitic acid) as did supplemented rats. To determine the mechanism for the increased synthesis, the activities of the following enzymes were determined in the cytoplasmic fraction of testicular homogenates: fatty acid synthetase, acetyl CoA carboxylase [EC 6.4.1.2], citrate-cleavage [EC 4.1.3.8], malic [EC 1.1.1.38], and the glucose-l-phosphate dehydrogenase [EC 1.1.1.49]: 6-phosphogluconate dehydrogenase pair [EC 1.1.1.44]. Although the activity of fatty acid synthetase did increase in livers from fat-deficient rats, no change was observed in corresponding testes. No difference between the two groups could be demonstrated in testicular activity of citrate-cleavage enzyme, malic enzyme, or the glucose-6-phosphate dehydrogenase: 6-phosphogluconate dehydrogenase pair. However, the activity of cytoplasmic acetyl CoA carboxylase in testes of rats fed the fat-deficient diet was 1.4 times higher than the activity in testes of rats fed the supplemented diet. Fat deficiency did not affect the specific activity of the testicular microsomal elongation system, assayed by incubation with 14C-malonyl CoA. The concentration of unesterified fatty acids was lower in testes of the fat-deficient compared to supplemented rats, indicating that decreased inhibition of acetyl CoA carboxylase in the fat-deficient rats testes might have been responsible for the observed increased de novo synthesis of palmitic acid."}
{"id": "PMID:13169", "title": "Induction of pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats.", "content": "The effectiveness of dietary and hormonal treatments in inducing several pyridoxal phosphate-(PLP)-dependent enzymes has been examined in vitamin B-6 deficient rats. Holo- and apoenzymes of serine dehydratase and ornithine aminotransferase were inducible in both control and deficient rats by feeding them 80% casein diets or by injecting them with glucagon. Holo- and apotyrosine aminotransferase were induced in both control and deficient rats by injecting them with glucagon or with dexamethasone phosphate. Phosphoenolpyruvate carboxykinase, a non-PLP-dependent enzyme, was inducible in both control and deficient rats by glucagon treatment if the rats were fed, but not if they had been starved. The degree of induction of certain enzymes depended upon whether rats were fed ad libitum, starved overnight, or fed a protein-free diet prior to the induction period. Phosphoenolpyruvate carboxykinase activities were about the same in both control and deficient rats. In vitamin B-6 deficient rats, both uninduced and induced activities of serine dehydratase, ornithine aminotransferase, and tyrosine aminotransferase assayed in the prsence of PLP, but not in its absence, either equaled or exceeded control values under most experimental conditions. Synthesis of excess of apoenzyme of PLP-dependent enzymes generally accounted for the high total enzyme activity in deficient rats. Differences between values for control and deficient rats could not be accounted for by differences in liver cyclic AMP concentrations nor were they apparently related to reduced food intake of the deficient rats. High apoenzyme concentration during depletion of coenzyme would tend to prevent depletion of active enzyme.", "contents": "Induction of pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. The effectiveness of dietary and hormonal treatments in inducing several pyridoxal phosphate-(PLP)-dependent enzymes has been examined in vitamin B-6 deficient rats. Holo- and apoenzymes of serine dehydratase and ornithine aminotransferase were inducible in both control and deficient rats by feeding them 80% casein diets or by injecting them with glucagon. Holo- and apotyrosine aminotransferase were induced in both control and deficient rats by injecting them with glucagon or with dexamethasone phosphate. Phosphoenolpyruvate carboxykinase, a non-PLP-dependent enzyme, was inducible in both control and deficient rats by glucagon treatment if the rats were fed, but not if they had been starved. The degree of induction of certain enzymes depended upon whether rats were fed ad libitum, starved overnight, or fed a protein-free diet prior to the induction period. Phosphoenolpyruvate carboxykinase activities were about the same in both control and deficient rats. In vitamin B-6 deficient rats, both uninduced and induced activities of serine dehydratase, ornithine aminotransferase, and tyrosine aminotransferase assayed in the prsence of PLP, but not in its absence, either equaled or exceeded control values under most experimental conditions. Synthesis of excess of apoenzyme of PLP-dependent enzymes generally accounted for the high total enzyme activity in deficient rats. Differences between values for control and deficient rats could not be accounted for by differences in liver cyclic AMP concentrations nor were they apparently related to reduced food intake of the deficient rats. High apoenzyme concentration during depletion of coenzyme would tend to prevent depletion of active enzyme."}
{"id": "PMID:13170", "title": "Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs.", "content": "The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was added to a casein-sucrose-soybean oil basal diet for rats or a stock diet with 2% soybean oil for guinea pigs. The effect of vitamin E and cholestyramine was also examined in some experiments. Cholesterol feeding increased the rate of lipid peroxidation in liver and aortic homogenate both in rats and guinea pigs when fed non-vitamin E supplemented basal diets. Vitamin E supplementation prevented the increase in the aorta, but not as completely in the liver in rats, while the reverse was true in guinea pigs. The effect of cholestyramine was dependent on the level of vitamin E in the diet. Cholesterol feeding decreased glutathione peroxidase activities in rats and guinea pigs. In guinea pigs, cholesterol feeding also markedly decreased liver microsomal NADPH-dependent lipid peroxidation, codein hydroxylation and cytochrome P-450 levels especially when fed non-vitamin E supplemented basal diets. In rats, cholesterol feeding reduced liver microsomal NADPH-dependent lipid peroxidation and in some cases, increased microsomal codeine hydroxylation activities, but had no effect on microsomal cytochrome P-450 levels. Vitamin E supplementation increased liver and serum cholesterol levels in guinea pigs, but had no such effect in rats. Results of this study indicate that cholesterol feeding can result in various metabolic alterations in rats and guinea pigs. The implication of these alterations in atherogenesis requires further investigations.", "contents": "Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs. The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was added to a casein-sucrose-soybean oil basal diet for rats or a stock diet with 2% soybean oil for guinea pigs. The effect of vitamin E and cholestyramine was also examined in some experiments. Cholesterol feeding increased the rate of lipid peroxidation in liver and aortic homogenate both in rats and guinea pigs when fed non-vitamin E supplemented basal diets. Vitamin E supplementation prevented the increase in the aorta, but not as completely in the liver in rats, while the reverse was true in guinea pigs. The effect of cholestyramine was dependent on the level of vitamin E in the diet. Cholesterol feeding decreased glutathione peroxidase activities in rats and guinea pigs. In guinea pigs, cholesterol feeding also markedly decreased liver microsomal NADPH-dependent lipid peroxidation, codein hydroxylation and cytochrome P-450 levels especially when fed non-vitamin E supplemented basal diets. In rats, cholesterol feeding reduced liver microsomal NADPH-dependent lipid peroxidation and in some cases, increased microsomal codeine hydroxylation activities, but had no effect on microsomal cytochrome P-450 levels. Vitamin E supplementation increased liver and serum cholesterol levels in guinea pigs, but had no such effect in rats. Results of this study indicate that cholesterol feeding can result in various metabolic alterations in rats and guinea pigs. The implication of these alterations in atherogenesis requires further investigations."}
{"id": "PMID:13171", "title": "Role of ascorbic acid on tyrosine hydroxylase activity in the adrenal gland of guinea pig.", "content": "The decrease of tyrosine hydroxylase activity in adrenal homogenate in scurvy was recovered after the administration of ascorbic acid. The causes of the increase in the enzyme activity after the administration of ascorbic acid have been studied. 1. No significant elevation in the enzyme activity was observed after the administration of reserpine to the scortutic guinea pig. 2. A dose of metal chelating agent, alpha, alpha'-dipyridyl, prevented the ascorbic acid-induced or reserpine-induced increase in enzyme activity in the scorbutic and the non-scorbutic guinea pigs, respectively. 3. Tyrosine hydroxylase activity was partially recovered by the administration of FeSO4 to the scorbutic guinea pig. From these results, it became clear that the induction of tyrosine hydroxylase which was not observed in scurvy was due to the deficiency of Fe2+. These results suggested that ascorbic acid affected the induction of this enzyme via Fe2+.", "contents": "Role of ascorbic acid on tyrosine hydroxylase activity in the adrenal gland of guinea pig. The decrease of tyrosine hydroxylase activity in adrenal homogenate in scurvy was recovered after the administration of ascorbic acid. The causes of the increase in the enzyme activity after the administration of ascorbic acid have been studied. 1. No significant elevation in the enzyme activity was observed after the administration of reserpine to the scortutic guinea pig. 2. A dose of metal chelating agent, alpha, alpha'-dipyridyl, prevented the ascorbic acid-induced or reserpine-induced increase in enzyme activity in the scorbutic and the non-scorbutic guinea pigs, respectively. 3. Tyrosine hydroxylase activity was partially recovered by the administration of FeSO4 to the scorbutic guinea pig. From these results, it became clear that the induction of tyrosine hydroxylase which was not observed in scurvy was due to the deficiency of Fe2+. These results suggested that ascorbic acid affected the induction of this enzyme via Fe2+."}
{"id": "PMID:13172", "title": "The effect of C.P.A.P. upon pulmonary reserve and cardiac output under increased abdominal pressure.", "content": "The cardiopulmonary effects of CPAP under conditions of increased intra-abdominal pressure were studied using the rabbit as an experimental model. Central venous pressure and cardiac output were reduced when the intra-abdominal pressure was increased. Addition of CPAP caused a further reduction in C.V.P. and C.O. Despite these reductions CPAP significantly improved arterial PaO2 without significant effects on pH and PaCO2. The use of CPAP in conditions associated with pulmonary dysfunction secondary to increased intraabdominal pressure may be a definite therapeutic modality.", "contents": "The effect of C.P.A.P. upon pulmonary reserve and cardiac output under increased abdominal pressure. The cardiopulmonary effects of CPAP under conditions of increased intra-abdominal pressure were studied using the rabbit as an experimental model. Central venous pressure and cardiac output were reduced when the intra-abdominal pressure was increased. Addition of CPAP caused a further reduction in C.V.P. and C.O. Despite these reductions CPAP significantly improved arterial PaO2 without significant effects on pH and PaCO2. The use of CPAP in conditions associated with pulmonary dysfunction secondary to increased intraabdominal pressure may be a definite therapeutic modality."}
{"id": "PMID:13173", "title": "Oral factitious injuries.", "content": "The subject of oral factitious injuries is reviewed and four cases are reported. It is noted that self-inflicted oral injuries are not limited to the soft tissue but may result in destruction of bone and tooth structure. While children are more often the subjects of self-injurious behavior about the oral cavity, adults may also exhibit similar conduct. Emotional problems are often co-existent with self-inflicted oral injuries, however, in some cases there does not seem to be a readily descernible emotional disturbance. Since factitious injuries often pose diagnostic problems for the dentist, some diagnostic suggestions are included.", "contents": "Oral factitious injuries. The subject of oral factitious injuries is reviewed and four cases are reported. It is noted that self-inflicted oral injuries are not limited to the soft tissue but may result in destruction of bone and tooth structure. While children are more often the subjects of self-injurious behavior about the oral cavity, adults may also exhibit similar conduct. Emotional problems are often co-existent with self-inflicted oral injuries, however, in some cases there does not seem to be a readily descernible emotional disturbance. Since factitious injuries often pose diagnostic problems for the dentist, some diagnostic suggestions are included."}
{"id": "PMID:13174", "title": "Acute anti-inflammatory effects of aspirin and dexamethasone in rats deprived of endogenous prostaglandin precursors.", "content": "Paw oedema, induced by carrageenan, was potentiated in normal rats by arachidonic acid and bishomo-gamma-linoleic acid, but not by 5,8,11-eicosatrienoic acid. The latter is not an endogenous prostaglandin precursor, but replaces the other two in essential fatty acid deficient (EFAD) rats. Carrageenan oedema was partially suppressed in these EFAD rats. Aspirin exhibited equal suppression of carrageenan oedema in both normal and EFAD rats, despite the fact that, in the latter, prostaglandins are of negligible importance. The anti-inflammatory effect of dexamethasone was also identical in both normal and EFAD rats. The view that interference with the prostaglandin-system explains the acute anti-inflammatory effects of the two drugs, is discussed, in relation to the present results.", "contents": "Acute anti-inflammatory effects of aspirin and dexamethasone in rats deprived of endogenous prostaglandin precursors. Paw oedema, induced by carrageenan, was potentiated in normal rats by arachidonic acid and bishomo-gamma-linoleic acid, but not by 5,8,11-eicosatrienoic acid. The latter is not an endogenous prostaglandin precursor, but replaces the other two in essential fatty acid deficient (EFAD) rats. Carrageenan oedema was partially suppressed in these EFAD rats. Aspirin exhibited equal suppression of carrageenan oedema in both normal and EFAD rats, despite the fact that, in the latter, prostaglandins are of negligible importance. The anti-inflammatory effect of dexamethasone was also identical in both normal and EFAD rats. The view that interference with the prostaglandin-system explains the acute anti-inflammatory effects of the two drugs, is discussed, in relation to the present results."}
{"id": "PMID:13175", "title": "Dihydroxylated metabolites of cannabinol formed by rat liver in vitro.", "content": "Cannabinol (CBN) was metabolized in vitro by a 10,000 g supernatant from rat liver. After removal of unchanged CBN and its monohydroxylated metabolites four dihydroxylated metabolites were isolated. By nuclear magnetic resonance and mass spectrometry the compounds were identified as 1'',7-dihydroxy-CBN. Side chain hydroxylation occurred predominantly at C-4'' anc C-3''.", "contents": "Dihydroxylated metabolites of cannabinol formed by rat liver in vitro. Cannabinol (CBN) was metabolized in vitro by a 10,000 g supernatant from rat liver. After removal of unchanged CBN and its monohydroxylated metabolites four dihydroxylated metabolites were isolated. By nuclear magnetic resonance and mass spectrometry the compounds were identified as 1'',7-dihydroxy-CBN. Side chain hydroxylation occurred predominantly at C-4'' anc C-3''."}
{"id": "PMID:13176", "title": "Oxidation of aliphatic hydroxylamines in aqueous solutions.", "content": "The effects of pH, buffer constituents, duration of storage, presence of air, heavy metal ions, extracting solvents and various additives and cofactors on the aerial oxidation of some aliphatic primary and secondary hydroxylamines were investigated. Copper ions were particularly effective catalysts of the oxidation reaction. Conditions to minimize this transformation are described.", "contents": "Oxidation of aliphatic hydroxylamines in aqueous solutions. The effects of pH, buffer constituents, duration of storage, presence of air, heavy metal ions, extracting solvents and various additives and cofactors on the aerial oxidation of some aliphatic primary and secondary hydroxylamines were investigated. Copper ions were particularly effective catalysts of the oxidation reaction. Conditions to minimize this transformation are described."}
{"id": "PMID:13177", "title": "Black lipid membranes as a model for intestinal absorption of drugs.", "content": "Black lipid membranes were generated in isotonic buffer (pH 4-5 and pH 6-5) from egg phosphatidylcholine and intestinal lipid, and the permeability to salicylamide, salicylic acid, p-aminobenzoic acid and tryptophan of these membranes was studied. Electrical resistance of intestinal lipid membranes was higher than that of phosphatidylcholine membranes. The presence of cholesterol produced an increase in the electrical resistance of black lipid membranes and a small decrease in the permeability of membranes to drugs. The permeability coefficient of salicylamide, an uncharged drug, was much larger than the coefficients of the charged drugs examined. The values for salicylic acid and p-aminobenzoic acid were much larger than comparable values predicted from their partition coefficients. Intestinal lipid membranes were more permeable to acidic drugs than phosphatidylcholine membranes. It is suggested that phospholipids and other lipid components of the small intestine may play an important role in the membrane permeability to acidic drugs. This method may be of interest in studying the complex processes of drug absorption from intestine.", "contents": "Black lipid membranes as a model for intestinal absorption of drugs. Black lipid membranes were generated in isotonic buffer (pH 4-5 and pH 6-5) from egg phosphatidylcholine and intestinal lipid, and the permeability to salicylamide, salicylic acid, p-aminobenzoic acid and tryptophan of these membranes was studied. Electrical resistance of intestinal lipid membranes was higher than that of phosphatidylcholine membranes. The presence of cholesterol produced an increase in the electrical resistance of black lipid membranes and a small decrease in the permeability of membranes to drugs. The permeability coefficient of salicylamide, an uncharged drug, was much larger than the coefficients of the charged drugs examined. The values for salicylic acid and p-aminobenzoic acid were much larger than comparable values predicted from their partition coefficients. Intestinal lipid membranes were more permeable to acidic drugs than phosphatidylcholine membranes. It is suggested that phospholipids and other lipid components of the small intestine may play an important role in the membrane permeability to acidic drugs. This method may be of interest in studying the complex processes of drug absorption from intestine."}
{"id": "PMID:13178", "title": "Hydrolysis of digoxin by acid.", "content": "Predictable hydrolysis of [3H]digoxin-12alpha occurred in vitro with incubation in HCl or gastric juice. Hydrolysis varied with pH, time, temperature and agitation. Digoxin, the bis- and mono-digitoxosides of digoxigenin and digoxigenin were separated by silica gel thin-layer chromatography using chloroform-ethyl acetate-glacial acetic acid (25:25:1 v/v) and were quantitated by liquid scintillation spectrometry. Hydrolysis with incubation at 37 degrees and pH 3 for 90 min was minimal, but increased with increasing acidity until greater than 70% was hydrolysed at pH 1-2 after 30 min and greater than 96% after 90 min incubation. At pH 0-9, 87% was hydrolysed after 30 min. In vitro hydrolysis in gastric fluid was slightly less than in HCl at the same pH. A volunteer was given 150 muCi[3H]digoxin-12alpha by nasogastric tube during a pentagastrin infusion when gastric pH was 0-94. He remained on his left side and samples were aspirated at intervals and immediately neutralized. Ethanol-chloroform 50-50 (v/v) extracts of the gastric fluid aspirated after 90 min and of all the urine specimens collected for 5 days were applied to a DEAE Sephadex LH-20 column. The radioactivity appeared in a single peak as digoxigenin in the 90 min gastric aspirate and in all urine specimens. Extensive intragastric hydrolysis of digoxin may occur under conditions of maximum acid output.", "contents": "Hydrolysis of digoxin by acid. Predictable hydrolysis of [3H]digoxin-12alpha occurred in vitro with incubation in HCl or gastric juice. Hydrolysis varied with pH, time, temperature and agitation. Digoxin, the bis- and mono-digitoxosides of digoxigenin and digoxigenin were separated by silica gel thin-layer chromatography using chloroform-ethyl acetate-glacial acetic acid (25:25:1 v/v) and were quantitated by liquid scintillation spectrometry. Hydrolysis with incubation at 37 degrees and pH 3 for 90 min was minimal, but increased with increasing acidity until greater than 70% was hydrolysed at pH 1-2 after 30 min and greater than 96% after 90 min incubation. At pH 0-9, 87% was hydrolysed after 30 min. In vitro hydrolysis in gastric fluid was slightly less than in HCl at the same pH. A volunteer was given 150 muCi[3H]digoxin-12alpha by nasogastric tube during a pentagastrin infusion when gastric pH was 0-94. He remained on his left side and samples were aspirated at intervals and immediately neutralized. Ethanol-chloroform 50-50 (v/v) extracts of the gastric fluid aspirated after 90 min and of all the urine specimens collected for 5 days were applied to a DEAE Sephadex LH-20 column. The radioactivity appeared in a single peak as digoxigenin in the 90 min gastric aspirate and in all urine specimens. Extensive intragastric hydrolysis of digoxin may occur under conditions of maximum acid output."}
{"id": "PMID:13179", "title": "The effect of compression on some physical properties of microcrystalline cellulose powders.", "content": "Tablets have been prepared from previously characterized microcrystalline cellulose (Avicel) powders, using an instrumented single station tablet machine. The regenerated particle size was found to increase in compaction pressure. Compaction caused a slight initial decrease in B.E.T. surface area, followed by an increase mainly as a result of elastic recovery of the particles. The intra-particulate pore size distribution showed no change throughout the range of compaction pressures studied, demonstrating that the internal pores did not collapse. Measurement of the interparticulate porosity by mercury porosimetry, liquid penetration techniques and scanning electron microscopy showed a decrease in this parameter with increase in compaction pressure. The dissolution behaviour from the compacts showed in general a decreased rate with increase in compaction pressure, that from the cellulose grade PH 105 being slower than from the remaining grades.", "contents": "The effect of compression on some physical properties of microcrystalline cellulose powders. Tablets have been prepared from previously characterized microcrystalline cellulose (Avicel) powders, using an instrumented single station tablet machine. The regenerated particle size was found to increase in compaction pressure. Compaction caused a slight initial decrease in B.E.T. surface area, followed by an increase mainly as a result of elastic recovery of the particles. The intra-particulate pore size distribution showed no change throughout the range of compaction pressures studied, demonstrating that the internal pores did not collapse. Measurement of the interparticulate porosity by mercury porosimetry, liquid penetration techniques and scanning electron microscopy showed a decrease in this parameter with increase in compaction pressure. The dissolution behaviour from the compacts showed in general a decreased rate with increase in compaction pressure, that from the cellulose grade PH 105 being slower than from the remaining grades."}
{"id": "PMID:13180", "title": "The action of colloidal silicon dioxide as a glidant for lactose, paracetamol, oxytetracycline and their mixtures.", "content": "Anomalies are observed in some of the physical and mechanical properties of mixtures of lactose, paracetamol and oxytetracycline when small amounts of colloidal silicon dioxide are added to them. Owing to its differing propensities to coat the particles of the host powders, the silicon dioxide acts as a glidant for the lactose and paracetamol, but as an antiglidant for the oxytetracycline.", "contents": "The action of colloidal silicon dioxide as a glidant for lactose, paracetamol, oxytetracycline and their mixtures. Anomalies are observed in some of the physical and mechanical properties of mixtures of lactose, paracetamol and oxytetracycline when small amounts of colloidal silicon dioxide are added to them. Owing to its differing propensities to coat the particles of the host powders, the silicon dioxide acts as a glidant for the lactose and paracetamol, but as an antiglidant for the oxytetracycline."}
{"id": "PMID:13193", "title": "Brain areas involved in the catecholamine mediated regulation of electroshock seizure intensity.", "content": "Selective treatments which alter the catecholamine content of discrete areas of the brain were tested for their effect on electroshock seizure intensity in the rat. The data indicate that depletion of noradrenaline and dopamine in near ventricular areas by the intracerebroventricular administration of the benzoquinolizine, Ro 4-1284, enhances electroshock seizure intensity. The enhancement of seizure produced by systemic Ro 4-1284 was antagonized by the intracerebroventricular injection of noradrenaline or dopamine which do not appear to penetrate more than 1 mm into the brain. Further, pretreatment with systemic iproniazid and L-dopa completely antagonized the increased seizure intensity produced by intracerebroventricular Ro 4-1284 and repleted brain catecholamines in both near and far ventricular areas. Thus, the effects of both noradrenaline and dopamine in attenuating electroshock seizure intensity appear to be exerted principally through periventricular structures.", "contents": "Brain areas involved in the catecholamine mediated regulation of electroshock seizure intensity. Selective treatments which alter the catecholamine content of discrete areas of the brain were tested for their effect on electroshock seizure intensity in the rat. The data indicate that depletion of noradrenaline and dopamine in near ventricular areas by the intracerebroventricular administration of the benzoquinolizine, Ro 4-1284, enhances electroshock seizure intensity. The enhancement of seizure produced by systemic Ro 4-1284 was antagonized by the intracerebroventricular injection of noradrenaline or dopamine which do not appear to penetrate more than 1 mm into the brain. Further, pretreatment with systemic iproniazid and L-dopa completely antagonized the increased seizure intensity produced by intracerebroventricular Ro 4-1284 and repleted brain catecholamines in both near and far ventricular areas. Thus, the effects of both noradrenaline and dopamine in attenuating electroshock seizure intensity appear to be exerted principally through periventricular structures."}
{"id": "PMID:13196", "title": "Simultaneous determination of 4-nitroanisole, 4-nitrophenol, and 4-nitrocatechol by phase-sensitive ac polarography.", "content": "Phase-sensitive ac polarography was applied to the simultaneous quantitative determination of 4-nitroanisole, 4-nitrophenol, and 4-nitrocatechol in alkaline solutions. Certain experimental precautions are necessary to determine each compound in the presence of the other two. Thus, 4-nitrocatechol is determined indirectly by forming a yellow ratio chelate with cupric ions, wheras 4-nitroansole is determined directly by the reduction waves of the nitro group. For the determination of 4-nitrophenol, the interferency by the simultaneously present 4-nitrocatechol must be eliminated by masking it by the addition of magnesium ions. The method described permits a qualitative and quantitative analysis of all three compounds in one solution since linear calibration curves are obtained.", "contents": "Simultaneous determination of 4-nitroanisole, 4-nitrophenol, and 4-nitrocatechol by phase-sensitive ac polarography. Phase-sensitive ac polarography was applied to the simultaneous quantitative determination of 4-nitroanisole, 4-nitrophenol, and 4-nitrocatechol in alkaline solutions. Certain experimental precautions are necessary to determine each compound in the presence of the other two. Thus, 4-nitrocatechol is determined indirectly by forming a yellow ratio chelate with cupric ions, wheras 4-nitroansole is determined directly by the reduction waves of the nitro group. For the determination of 4-nitrophenol, the interferency by the simultaneously present 4-nitrocatechol must be eliminated by masking it by the addition of magnesium ions. The method described permits a qualitative and quantitative analysis of all three compounds in one solution since linear calibration curves are obtained."}
{"id": "PMID:13197", "title": "Kinetics of hydrolysis of fenclorac.", "content": "The kinetics of hydrolysis of fenclorac were studied to determine its stability in aqueous solution at different pH's and temperatures. For this study, a stability-specific liquid chromatographic assay method was developed to separate fenclorac from its hydrolysis product, alpha-hydroxy-3-chloro-4-cyclohexylbenzeneacetic acid. The k-pH profile in the 0-12 pH range in various buffer solutions shows that fenclorac is stable in its undissociated form in strongly acidic media and is unstable in neutral and alkaline media. The instability of fenclorac in aqueous solution is proportional to the degree of ionization of the carboxyl group in the 1-4 pH range and is independent of pH above 4. The rate-determining step in the mechanism of hydrolysis of fenclorac involves ionization of the carbon-chlorine bond. The ionization is catalyzed by an intramolecular necleophilic attack on the alpha-carbon by the dissociated carboxyl group, resulting in the formation of an unstable intermediate, a three-membered ring lactone. This unstable intermediate rapidly hydrolyzes to the final hydrolysis product. This mechanism is supported by experimental evidence such as the medium effect, positive salt effect, common ion effect, and substituent effect. Arrhenius parameters for the hydrolysis of fenclorac and its 3-nitro substituted analog were obtained.", "contents": "Kinetics of hydrolysis of fenclorac. The kinetics of hydrolysis of fenclorac were studied to determine its stability in aqueous solution at different pH's and temperatures. For this study, a stability-specific liquid chromatographic assay method was developed to separate fenclorac from its hydrolysis product, alpha-hydroxy-3-chloro-4-cyclohexylbenzeneacetic acid. The k-pH profile in the 0-12 pH range in various buffer solutions shows that fenclorac is stable in its undissociated form in strongly acidic media and is unstable in neutral and alkaline media. The instability of fenclorac in aqueous solution is proportional to the degree of ionization of the carboxyl group in the 1-4 pH range and is independent of pH above 4. The rate-determining step in the mechanism of hydrolysis of fenclorac involves ionization of the carbon-chlorine bond. The ionization is catalyzed by an intramolecular necleophilic attack on the alpha-carbon by the dissociated carboxyl group, resulting in the formation of an unstable intermediate, a three-membered ring lactone. This unstable intermediate rapidly hydrolyzes to the final hydrolysis product. This mechanism is supported by experimental evidence such as the medium effect, positive salt effect, common ion effect, and substituent effect. Arrhenius parameters for the hydrolysis of fenclorac and its 3-nitro substituted analog were obtained."}
{"id": "PMID:13198", "title": "The interaction of histamine and guanylnucleotides with cardiac adenylate cyclase and its relationship to cardiac contractility.", "content": "Histamine stimulates adenylate cyclase activity in a washed membrane preparation from guinea-pig ventricle. Marked synergistic effects are observed with histamine and GTP. In the absence of GTP, the degree of stimulation of the enzyme by histamine is slight and occurs only in the presence of relatively high concentrations of ATP suggesting that ATP, or contaminating GTP in commercial preparations of ATP, may partially satisfy the guanylnucleotide requirement. The GTP analog, GppNHp, strongly and irreversibly activates the cardiac enzyme. Preincubation studies, in which the membranes are treated with GppNHp alone or in combination with histamine followed by estensive washing, indicate that histamine markedly increases the rate of activation of the enzyme by the guanylnucleotide. It is suggested that the mechanism of action of histamine on adenylate cyclase involves a facilitation of the interaction of guanylnucleotides with the regulatory site of the enzyme. The relative activities for stimulation of adenylate cyclase of a series of histamine analogs correlate quite well with the activities of these derivatives on four H2-receptor systems, including atrial rate and ventricular contractility and do not correlate with the activities on H1-receptors. The H2-receptor antagonists, burimamide and metiamide, competitively inhibit hitamine-stimulated adenylate cyclase and the dissociation constants for these antagonists on the enzyme agree with the pharmacological data on the H2-receptors in the atria and ventricles. Our results suggest that histamine-stimulated cardiac adenylate cyclase can be classified inotorpic and chronotropic effects of histamine on the intact heart.", "contents": "The interaction of histamine and guanylnucleotides with cardiac adenylate cyclase and its relationship to cardiac contractility. Histamine stimulates adenylate cyclase activity in a washed membrane preparation from guinea-pig ventricle. Marked synergistic effects are observed with histamine and GTP. In the absence of GTP, the degree of stimulation of the enzyme by histamine is slight and occurs only in the presence of relatively high concentrations of ATP suggesting that ATP, or contaminating GTP in commercial preparations of ATP, may partially satisfy the guanylnucleotide requirement. The GTP analog, GppNHp, strongly and irreversibly activates the cardiac enzyme. Preincubation studies, in which the membranes are treated with GppNHp alone or in combination with histamine followed by estensive washing, indicate that histamine markedly increases the rate of activation of the enzyme by the guanylnucleotide. It is suggested that the mechanism of action of histamine on adenylate cyclase involves a facilitation of the interaction of guanylnucleotides with the regulatory site of the enzyme. The relative activities for stimulation of adenylate cyclase of a series of histamine analogs correlate quite well with the activities of these derivatives on four H2-receptor systems, including atrial rate and ventricular contractility and do not correlate with the activities on H1-receptors. The H2-receptor antagonists, burimamide and metiamide, competitively inhibit hitamine-stimulated adenylate cyclase and the dissociation constants for these antagonists on the enzyme agree with the pharmacological data on the H2-receptors in the atria and ventricles. Our results suggest that histamine-stimulated cardiac adenylate cyclase can be classified inotorpic and chronotropic effects of histamine on the intact heart."}
{"id": "PMID:13199", "title": "Pharmacologically induced changes in the 3':5'-cyclic guanosine monophosphate content of rat cerebellar cortex: difference between apomorphine, haloperidol and harmaline.", "content": "Harmaline increases cerebellar 3':5'-cyclic guanosine monophosphate (cGMP) content in a dose-related manner; this increase is prevented by a pretreatment with 3-acetylpyridine (3-AP) (0.66 mmol/kg) which destroys climbing fibers and inhibits harmaline-induced tremor. The cerebellar cGMP content increases after isoniazid; this response remains unchanged in rats pretreated with 3-AP. Since isoniazid decreases cerebellar gamma-aminobuturic acid (GABA) levels, the increase in cGMP content might reflect a reduction in the availability of GABA at the level of postsynaptic receptors. Apomorphine (a dopamine receptor agonist) and haloperidol (a dopamine receptor blocker) increase or decrease the cGMP content of cerebellar cortex, respectively. Neither drug changes the guanylate cyclase activity of cerebellar homogenates; moreover their action on cerebellar cGMP content persists after 3-AP. Chloropromazine, like haloperidol, decreases the cerebellar cGMP content. The increase in cerebellar cGMP content elicited by apomorphine can be differentiated from that elicited by harmaline or isoniazid; presumably apomorphine indirectly activates mossy fibers. The decrease in cerebellar cGMP content elicited by haloperidol can be differentiated from that elicited by diazepam; perhaps haloperidol reduces the mossy fiber input to the cerebellum. We suggest that the cGMP content of cerebellar cortex fluctuates in response to changes in the afferent stimulatory input to the cerebellum; it increases when the activity of either climbing or mossy fibers is increased; it decreases when either of these two stimulatory inputs is reduced.", "contents": "Pharmacologically induced changes in the 3':5'-cyclic guanosine monophosphate content of rat cerebellar cortex: difference between apomorphine, haloperidol and harmaline. Harmaline increases cerebellar 3':5'-cyclic guanosine monophosphate (cGMP) content in a dose-related manner; this increase is prevented by a pretreatment with 3-acetylpyridine (3-AP) (0.66 mmol/kg) which destroys climbing fibers and inhibits harmaline-induced tremor. The cerebellar cGMP content increases after isoniazid; this response remains unchanged in rats pretreated with 3-AP. Since isoniazid decreases cerebellar gamma-aminobuturic acid (GABA) levels, the increase in cGMP content might reflect a reduction in the availability of GABA at the level of postsynaptic receptors. Apomorphine (a dopamine receptor agonist) and haloperidol (a dopamine receptor blocker) increase or decrease the cGMP content of cerebellar cortex, respectively. Neither drug changes the guanylate cyclase activity of cerebellar homogenates; moreover their action on cerebellar cGMP content persists after 3-AP. Chloropromazine, like haloperidol, decreases the cerebellar cGMP content. The increase in cerebellar cGMP content elicited by apomorphine can be differentiated from that elicited by harmaline or isoniazid; presumably apomorphine indirectly activates mossy fibers. The decrease in cerebellar cGMP content elicited by haloperidol can be differentiated from that elicited by diazepam; perhaps haloperidol reduces the mossy fiber input to the cerebellum. We suggest that the cGMP content of cerebellar cortex fluctuates in response to changes in the afferent stimulatory input to the cerebellum; it increases when the activity of either climbing or mossy fibers is increased; it decreases when either of these two stimulatory inputs is reduced."}
{"id": "PMID:13200", "title": "Propoxyphene and norpropoxyphene: pharmacologic and toxic effects in animals.", "content": "alpha-d-Propoxyphene and its principle metabolite, alpha-d-norpropoxyphene, were compared pharmacologically to establish their relative opioid profiles as defined by naloxone reversal. Propoxyphene exhibited opioid activity in the following tests: mouse abdominal constriction and rat tail heat analgesic tests, inhibition of the twitch of the guinea-pig ileum and acute lethality in rodents. Norpropoxyphene also showed opioid activity in the rat tail heat and guinea-pig ileum tests, but exhibited nonopioid activity in the mouse abdominal constriction and acute toxicity studies. Jumping in mice, precipitated by naloxone, suggests the following order for liability to produce physical dependence after repeated administration: morphine greater than codeine greater than propoxyphene greater than norpropoxyphene approximately saline. Propoxyphene and norpropoxyphene depressed axonal conduction in isolated peripheral nerve and were comparable in potency to standard local anesthetic agents. The nonopioid actions of norpropoxyphene might be due in part to its local anesthetic properties.", "contents": "Propoxyphene and norpropoxyphene: pharmacologic and toxic effects in animals. alpha-d-Propoxyphene and its principle metabolite, alpha-d-norpropoxyphene, were compared pharmacologically to establish their relative opioid profiles as defined by naloxone reversal. Propoxyphene exhibited opioid activity in the following tests: mouse abdominal constriction and rat tail heat analgesic tests, inhibition of the twitch of the guinea-pig ileum and acute lethality in rodents. Norpropoxyphene also showed opioid activity in the rat tail heat and guinea-pig ileum tests, but exhibited nonopioid activity in the mouse abdominal constriction and acute toxicity studies. Jumping in mice, precipitated by naloxone, suggests the following order for liability to produce physical dependence after repeated administration: morphine greater than codeine greater than propoxyphene greater than norpropoxyphene approximately saline. Propoxyphene and norpropoxyphene depressed axonal conduction in isolated peripheral nerve and were comparable in potency to standard local anesthetic agents. The nonopioid actions of norpropoxyphene might be due in part to its local anesthetic properties."}
{"id": "PMID:13201", "title": "Reduction of tertiary amine N-oxides by rat liver mitochondria.", "content": "Reduction of tertiary amine N-oxides by the mitochondrial fraction of rat liver was investigated. NADPH was required as a cofactor. The rate of reaction was faster with the NADPH-generating system than with NADPH. Isocitrate in the NADPH-generating system revealed the maximum stimulation. A little less activity was observed when NADH was used as a cofactor instead of NADPH. The reductase activity was markedly inhibited under aerobic conditions. The rates of mitochondrial tertiary amine N-oxide reduction expressed in nanomoles per milligram of protein per minute were: N,N-dimethylaniline N-oxide, 4.3; tiaramide N-oxide, 0.47; and imipramine N-oxide, 0.14. The activity for N,N-dimethylaniline N-oxide was comparable to the microsomal activity, but the activity for imipramine N-oxide was much less than that in microsomes. Isocitrate and alpha-ketoglutarate were found to stimulate mitochondrial tertiary amine N-oxide reduction more efficiently than other Krebs cycle intermediates. Oxalacetate, on the other hand, was the least effective intermediate. ATP together with NADPH and NADP stimulated the reaction efficiently, probably due to the energy-dependent intramitochondrial transhydrogenation. Antimycin, rotenone and cyanide had little or no effect on isocitrate-dependent N-oxide reduction, whereas an inhibitory effect was observed on succinate-supported N-oxide reductase. N-oxide reductase activity in mitochondria was partially suppressed under an atmosphere of carbon monoxide, althouth no increase of the activity was observed by phenobarbital pretreatment, nor inhibition by 2,4-dichloro-6-phenylphenoxyethylamine. Experiments with digitonin-treated mitochondria demonstrated that mitochondrial N-oxide reductase was bound to mitochondrial inner membrane or its matrix.", "contents": "Reduction of tertiary amine N-oxides by rat liver mitochondria. Reduction of tertiary amine N-oxides by the mitochondrial fraction of rat liver was investigated. NADPH was required as a cofactor. The rate of reaction was faster with the NADPH-generating system than with NADPH. Isocitrate in the NADPH-generating system revealed the maximum stimulation. A little less activity was observed when NADH was used as a cofactor instead of NADPH. The reductase activity was markedly inhibited under aerobic conditions. The rates of mitochondrial tertiary amine N-oxide reduction expressed in nanomoles per milligram of protein per minute were: N,N-dimethylaniline N-oxide, 4.3; tiaramide N-oxide, 0.47; and imipramine N-oxide, 0.14. The activity for N,N-dimethylaniline N-oxide was comparable to the microsomal activity, but the activity for imipramine N-oxide was much less than that in microsomes. Isocitrate and alpha-ketoglutarate were found to stimulate mitochondrial tertiary amine N-oxide reduction more efficiently than other Krebs cycle intermediates. Oxalacetate, on the other hand, was the least effective intermediate. ATP together with NADPH and NADP stimulated the reaction efficiently, probably due to the energy-dependent intramitochondrial transhydrogenation. Antimycin, rotenone and cyanide had little or no effect on isocitrate-dependent N-oxide reduction, whereas an inhibitory effect was observed on succinate-supported N-oxide reductase. N-oxide reductase activity in mitochondria was partially suppressed under an atmosphere of carbon monoxide, althouth no increase of the activity was observed by phenobarbital pretreatment, nor inhibition by 2,4-dichloro-6-phenylphenoxyethylamine. Experiments with digitonin-treated mitochondria demonstrated that mitochondrial N-oxide reductase was bound to mitochondrial inner membrane or its matrix."}
{"id": "PMID:13202", "title": "In vitro inhibition of rho-aminohippurate transport by halogenated anesthetics.", "content": "The effects of four commonly used halogenated anesthetic agents (methoxyflurane, halothane, enflurane and fluroxene) on rho-aminohippurate (PAH) uptake by rabbit renal cortical slices were examined. All agents depressed PAH uptake in a linear dose-dependent manner after 60 minutes of incubation and the effect was reversible. When the data were normalized for anesthetic potency, all agents exhibited a parallel dose-response curve. Since these agents do not share a common metabolite, it is concluded that the depression of PAH transport is mediated primarily by a direct effect of the agents acting through a common pathway. Exposure of kidney slices to perithreshold concentrations of halothane and enflurane for 180 minutes did not result in a cumulative inhibitory effect on PAH transport. A slight time-dependent effect was seen with methoxyflurane. It is suggested that with prolonged exposure metabolic conversion of methoxyflurane may occur leading to further inhibition of PAH uptake.", "contents": "In vitro inhibition of rho-aminohippurate transport by halogenated anesthetics. The effects of four commonly used halogenated anesthetic agents (methoxyflurane, halothane, enflurane and fluroxene) on rho-aminohippurate (PAH) uptake by rabbit renal cortical slices were examined. All agents depressed PAH uptake in a linear dose-dependent manner after 60 minutes of incubation and the effect was reversible. When the data were normalized for anesthetic potency, all agents exhibited a parallel dose-response curve. Since these agents do not share a common metabolite, it is concluded that the depression of PAH transport is mediated primarily by a direct effect of the agents acting through a common pathway. Exposure of kidney slices to perithreshold concentrations of halothane and enflurane for 180 minutes did not result in a cumulative inhibitory effect on PAH transport. A slight time-dependent effect was seen with methoxyflurane. It is suggested that with prolonged exposure metabolic conversion of methoxyflurane may occur leading to further inhibition of PAH uptake."}
{"id": "PMID:13203", "title": "Intracellular pH of single crustacean muscle fibres by the DMO and electrode methods during acid and alkaline conditions.", "content": "1. The intracellular pH of intact single muscle fibres of the giant barnacle was measured directly with a glass micro-electrode following prolonged (2-5 hr) equilibration in one of three solutions: normal Ringer, CO2 Ringer and NH4+ Ringer. 2. The intracellular pH of identically-prepared fibres from the same specimen was measured indirectly from the distribution of DMO following prolonged equilibration in the same solutions. 3. The DMO-pH compared favourably with the electrode-pHi provided DMO-pHi was calculated from the values of the indicator compounds, [14C]DMO and [3H]inulin, obtained by extrapolating the slow uptake phase to time zero. 4. Following prolonged equilibration, the transmembrane H+ ion distribution was found to vary with the membrane potential but not in accordance with a simple Gibbs-Donnan equilibrium. 5. A model which recognizes the existence of two independent net fluxes for H+ across the membrane in developed to explain the results. One of the fluxes represents passive diffusion and the other represents the so called H+-pump. The model predicts the H+-pump rate increases by two orders of magnitude when pHi is reduced from 7-2 to 6-7.", "contents": "Intracellular pH of single crustacean muscle fibres by the DMO and electrode methods during acid and alkaline conditions. 1. The intracellular pH of intact single muscle fibres of the giant barnacle was measured directly with a glass micro-electrode following prolonged (2-5 hr) equilibration in one of three solutions: normal Ringer, CO2 Ringer and NH4+ Ringer. 2. The intracellular pH of identically-prepared fibres from the same specimen was measured indirectly from the distribution of DMO following prolonged equilibration in the same solutions. 3. The DMO-pH compared favourably with the electrode-pHi provided DMO-pHi was calculated from the values of the indicator compounds, [14C]DMO and [3H]inulin, obtained by extrapolating the slow uptake phase to time zero. 4. Following prolonged equilibration, the transmembrane H+ ion distribution was found to vary with the membrane potential but not in accordance with a simple Gibbs-Donnan equilibrium. 5. A model which recognizes the existence of two independent net fluxes for H+ across the membrane in developed to explain the results. One of the fluxes represents passive diffusion and the other represents the so called H+-pump. The model predicts the H+-pump rate increases by two orders of magnitude when pHi is reduced from 7-2 to 6-7."}
{"id": "PMID:13204", "title": "Chloride transport in human erythrocytes and ghosts: a quantitative comparison.", "content": "1. Homogeneous preparations of resealed ghosts with intracellular KCl concentrations between 15 and 900 mM could be prepared. Virtually all ghosts sealed to chloride. The chloride transport system was found not to be damaged: a quantitative comparison of the self-exchange of 36Cl- across intact and resealed membranes showed that both the transport capacity and a number of characteristic properties were identical (saturation kinetics, temperature dependence and the effect of inhibitors). 2. Due to the absence of intracellular titratable buffers intracellular chloride concentration in ghosts vary only slightly between pH5 and 11. The unidirectional exchange flux was constant between pH 7 and 11, showing that the transport system does not have a functionally important titratable group in the alkaline range, as previously assumed. The decrease of transport below pH 7 is similar in intact erythrocytes and ghosts. 3. Mean cellular volume of the resealed ghosts was a function of the amount of KCl added at 'reversal', before the ghosts are sealed. The ghosts shrank by osmosis when KCl was added to the suspension of 'unsealed' ghosts. The reflexion coefficient of sucrose (and therefore the osmotic effect) is larger than that of KCl. It was, therefore, possible to demonstrate that volume changes do not affect the chloride transport across the human red cell membrane. Unidirectional chloride fluxes at a KCl concentration of 165 mM were independent of ghost volume (100-40 mum3).", "contents": "Chloride transport in human erythrocytes and ghosts: a quantitative comparison. 1. Homogeneous preparations of resealed ghosts with intracellular KCl concentrations between 15 and 900 mM could be prepared. Virtually all ghosts sealed to chloride. The chloride transport system was found not to be damaged: a quantitative comparison of the self-exchange of 36Cl- across intact and resealed membranes showed that both the transport capacity and a number of characteristic properties were identical (saturation kinetics, temperature dependence and the effect of inhibitors). 2. Due to the absence of intracellular titratable buffers intracellular chloride concentration in ghosts vary only slightly between pH5 and 11. The unidirectional exchange flux was constant between pH 7 and 11, showing that the transport system does not have a functionally important titratable group in the alkaline range, as previously assumed. The decrease of transport below pH 7 is similar in intact erythrocytes and ghosts. 3. Mean cellular volume of the resealed ghosts was a function of the amount of KCl added at 'reversal', before the ghosts are sealed. The ghosts shrank by osmosis when KCl was added to the suspension of 'unsealed' ghosts. The reflexion coefficient of sucrose (and therefore the osmotic effect) is larger than that of KCl. It was, therefore, possible to demonstrate that volume changes do not affect the chloride transport across the human red cell membrane. Unidirectional chloride fluxes at a KCl concentration of 165 mM were independent of ghost volume (100-40 mum3)."}
{"id": "PMID:13205", "title": "Direct measurement of the intracellular pH of mammalian cardiac muscle.", "content": "1. The intracellular pH (pHi) of sheep heart Purkinje fibres and rat, ferret and guinea-pig ventricle has been measured using recessed-tip pH-sensitive micro-electrodes. 2. In the absence of CO2 the pHi was approximately 7-2 in all the preparations used. In 5% CO2 the mean pHi was 7-14 in rat and ferret ventricle and 7-02 in sheep Purkinje fibres. 3. The pHi response to an increase or a decrease in the CO2 level (at constant external pH) was biphasic with a large transient change followed by a partial recovery to a new sustained pHi. 4. The intracellular buffering capacity was 34-8 +/- 2-7 m-equiv H+/pH unit per l. (+/- S.E. of mean) in sheep Purkinje fibres, 76-6 +/- 13-6 in rat ventricle and approximately 69 in ferret ventricle. 5. The pHi of all the preparations tested indicated that H+ ions were not passively distributed across the cell membrane. There was also little or no pHi change produced by depolarization with high K solutions. 6. Short exposures to hypertonic solutions (100 mM sucrose or 50 mM-KCl) produced a decrease in pHi of approximately 0-1 pH units. 7. Acetazolamide slowed the pHi response to CO2 changes. 8. Restoration of the pHi after displacement by increasing the CO2 was not blocked by ouabain or SITS. 9. The relationship between pHi and cardiac contractility is discussed.", "contents": "Direct measurement of the intracellular pH of mammalian cardiac muscle. 1. The intracellular pH (pHi) of sheep heart Purkinje fibres and rat, ferret and guinea-pig ventricle has been measured using recessed-tip pH-sensitive micro-electrodes. 2. In the absence of CO2 the pHi was approximately 7-2 in all the preparations used. In 5% CO2 the mean pHi was 7-14 in rat and ferret ventricle and 7-02 in sheep Purkinje fibres. 3. The pHi response to an increase or a decrease in the CO2 level (at constant external pH) was biphasic with a large transient change followed by a partial recovery to a new sustained pHi. 4. The intracellular buffering capacity was 34-8 +/- 2-7 m-equiv H+/pH unit per l. (+/- S.E. of mean) in sheep Purkinje fibres, 76-6 +/- 13-6 in rat ventricle and approximately 69 in ferret ventricle. 5. The pHi of all the preparations tested indicated that H+ ions were not passively distributed across the cell membrane. There was also little or no pHi change produced by depolarization with high K solutions. 6. Short exposures to hypertonic solutions (100 mM sucrose or 50 mM-KCl) produced a decrease in pHi of approximately 0-1 pH units. 7. Acetazolamide slowed the pHi response to CO2 changes. 8. Restoration of the pHi after displacement by increasing the CO2 was not blocked by ouabain or SITS. 9. The relationship between pHi and cardiac contractility is discussed."}
{"id": "PMID:13210", "title": "[Dietary protein level and circadian variation of enzyme activities for glucose metabolism and lipogenesis in male rats (author's transl)].", "content": "One hundred and seven Wistar rats, 8 weeks old and weighing 180-200 g, were housed under conditions of controlled temperature (22 plus or minus 2 degrees) and lighting (light on from 07:00 to 19:00). They were divided into 2 groups and fed diets containing either 15 per cent cas-protein for 23 days. Food consumption was recorded every 2 hours for each animal during 48 hours. Four or five rats from each group were killed every 2 hours for 24 hours and the hepatic activities of PK (EC.2.7.1.40),G6P-DH (EC1.1.1.49), ME (EC1.1.1.40), Acetyl-CoA-carbox (EC.6.4.1.2.),PC(EC.6.4.1.1.), PEP-CK(EC.4.1.1.32), G6Pase (EC.3.1.3.9) and GPT (EC.2.6.1.2.) were measured...", "contents": "[Dietary protein level and circadian variation of enzyme activities for glucose metabolism and lipogenesis in male rats (author's transl)]. One hundred and seven Wistar rats, 8 weeks old and weighing 180-200 g, were housed under conditions of controlled temperature (22 plus or minus 2 degrees) and lighting (light on from 07:00 to 19:00). They were divided into 2 groups and fed diets containing either 15 per cent cas-protein for 23 days. Food consumption was recorded every 2 hours for each animal during 48 hours. Four or five rats from each group were killed every 2 hours for 24 hours and the hepatic activities of PK (EC.2.7.1.40),G6P-DH (EC1.1.1.49), ME (EC1.1.1.40), Acetyl-CoA-carbox (EC.6.4.1.2.),PC(EC.6.4.1.1.), PEP-CK(EC.4.1.1.32), G6Pase (EC.3.1.3.9) and GPT (EC.2.6.1.2.) were measured..."}
{"id": "PMID:13214", "title": "Studies on antianaphylactic agents. 5. Synthesis of 3-(1H-tetrazol-5-yl)chromones, a new series of antiallergic substances.", "content": "A number of 3-(1H-tetrazol-5-yl)chromones were synthesized and found to have antiallergic activity in the rat passive cutaneous anaphylaxis (PCA) test. These compounds are active when administered orally in rats and of possible value for the treatment of asthma.", "contents": "Studies on antianaphylactic agents. 5. Synthesis of 3-(1H-tetrazol-5-yl)chromones, a new series of antiallergic substances. A number of 3-(1H-tetrazol-5-yl)chromones were synthesized and found to have antiallergic activity in the rat passive cutaneous anaphylaxis (PCA) test. These compounds are active when administered orally in rats and of possible value for the treatment of asthma."}
{"id": "PMID:13215", "title": "Use of distribution coefficients in quantitative structure-activity relationships.", "content": "The use of distribution coefficients (log D) for the analysis of structure-activity relationships of ionizable compounds is described. (D is the ratio of the equilibrium concentration of compound in an organic phase to the total concentration of un-ionized and ionized species in the aqueous phase at a given pH.) Simpler equations, often with improved correlations, have resulted. This method has the advantage that the influence of pKa or equivalent electronic factors on distribution can be distinguished from electronic effects related to mechanism of action. Several absorption studies are reanalyzed as well as studies on membrane conductance and uncoupling of oxidative phosphorylation.", "contents": "Use of distribution coefficients in quantitative structure-activity relationships. The use of distribution coefficients (log D) for the analysis of structure-activity relationships of ionizable compounds is described. (D is the ratio of the equilibrium concentration of compound in an organic phase to the total concentration of un-ionized and ionized species in the aqueous phase at a given pH.) Simpler equations, often with improved correlations, have resulted. This method has the advantage that the influence of pKa or equivalent electronic factors on distribution can be distinguished from electronic effects related to mechanism of action. Several absorption studies are reanalyzed as well as studies on membrane conductance and uncoupling of oxidative phosphorylation."}
{"id": "PMID:13216", "title": "5,11-dimethyl-2,9-bis(phenylacetyl)-5,11-diazatetracyclo[6.2.2.0(2,7).0(4,9)]dodecane, a potent, novel analgesic.", "content": "5,11-Dimethyl-2,9-bis(phenylacetyl)-5,11-diazatetracyclo[6.2.2.0(2,7)90(4,9)]dodecane (2a) has been found to be a potent narcotic analgesic of unusual structure. All of the analgesic activity was attributable to the levorotatory isomer 2b which was approximately three times as potent as morphine in the rat. Removal of one N-methyl group from 2a reduced, but did not abolish, the analgesic activity. However N-allyl analogues were neither agonists nor antagonists. Replacement of one of the phenyls of 2a with a cyclohexyl group yielded an analogue with considerable activity. Structural similarities with derivatives of ethenooripavine are noted.", "contents": "5,11-dimethyl-2,9-bis(phenylacetyl)-5,11-diazatetracyclo[6.2.2.0(2,7).0(4,9)]dodecane, a potent, novel analgesic. 5,11-Dimethyl-2,9-bis(phenylacetyl)-5,11-diazatetracyclo[6.2.2.0(2,7)90(4,9)]dodecane (2a) has been found to be a potent narcotic analgesic of unusual structure. All of the analgesic activity was attributable to the levorotatory isomer 2b which was approximately three times as potent as morphine in the rat. Removal of one N-methyl group from 2a reduced, but did not abolish, the analgesic activity. However N-allyl analogues were neither agonists nor antagonists. Replacement of one of the phenyls of 2a with a cyclohexyl group yielded an analogue with considerable activity. Structural similarities with derivatives of ethenooripavine are noted."}
{"id": "PMID:13217", "title": "Ergoline congeners as potential inhibitors of prolactin release. 3. Derivatives of 3-phenylpiperidine.", "content": "In a continuation of our attempts to elucidate the prolactin release inhibiting pharmacophore within the ergoline structure, we have prepared several derivatives of 3-phenylpiperidine. These congeners have been evaluated for inhibition of prolactin release in vivo and are for the most part inactive.", "contents": "Ergoline congeners as potential inhibitors of prolactin release. 3. Derivatives of 3-phenylpiperidine. In a continuation of our attempts to elucidate the prolactin release inhibiting pharmacophore within the ergoline structure, we have prepared several derivatives of 3-phenylpiperidine. These congeners have been evaluated for inhibition of prolactin release in vivo and are for the most part inactive."}
{"id": "PMID:13218", "title": "Esters of 4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazieneethanol and related compounds as long-acting antipsychotic agents. Synthesis of the 1-adamantoate, the first crystalline base.", "content": "A number of new esters of fluphenazine are described: among these was the 1-adamantoate, 1h, the first highly crystalline ester of that drug. The 1-adamantoate of pipotiazine, 2b, typically, was an oil. Following a single subcutaneous or intramuscular injection of 25 mg/kg of either 1h or 2b, dissolved in sesame oil, each ester was found to be a potent and long-acting inhibitor of conditioned avoidance behavior in the rat.", "contents": "Esters of 4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazieneethanol and related compounds as long-acting antipsychotic agents. Synthesis of the 1-adamantoate, the first crystalline base. A number of new esters of fluphenazine are described: among these was the 1-adamantoate, 1h, the first highly crystalline ester of that drug. The 1-adamantoate of pipotiazine, 2b, typically, was an oil. Following a single subcutaneous or intramuscular injection of 25 mg/kg of either 1h or 2b, dissolved in sesame oil, each ester was found to be a potent and long-acting inhibitor of conditioned avoidance behavior in the rat."}
{"id": "PMID:13219", "title": "Relationships between opiate receptor binding and analgetic properties of prodine-type compounds.", "content": "The receptor binding affinities of some diastereoisomeric prodine analgoues have been compared with their analgetic activities determined by the hot-plate test in mice. The close correlation found between these potencies indicates that the relative analgetic activities of the alpha/beta isomers are determined primarily by the appropriate association to the receptor sites.", "contents": "Relationships between opiate receptor binding and analgetic properties of prodine-type compounds. The receptor binding affinities of some diastereoisomeric prodine analgoues have been compared with their analgetic activities determined by the hot-plate test in mice. The close correlation found between these potencies indicates that the relative analgetic activities of the alpha/beta isomers are determined primarily by the appropriate association to the receptor sites."}
{"id": "PMID:13221", "title": "Electrochemical potential of protons in vesicles reconstituted from purified, proton-translocating adenosine triphosphatase.", "content": "Measurements were made of the difference in the electrochemical potential of protons (delta-mu H+) across the membrane of vesicles restituted from the ATPase complex (TF0.F1) purified from a thermophilic bacterium and P-lipids. Two fluorescent dyes, anilinonaphthalene sulfonate (ANS) and 9-aminoacridine (9AA) were used as probes for measuring the membrane potential (delta psi) and pH difference across the membrane (delta pH), respectively. In the presence of Tris buffer the maximal delta psi ans no delta pH were produced, while in the presence of the permeant anion NO-3 the maximal delta pH and a low delta psi were produced by the addition of ATP. When thATP concentration was 0.24 mm, the delta psi was 140-150 mV (positive inside) in Tris buffer, and the delta pH was 2.9-3.5 units (acidic inside) in the presence of NO-3. Addition of a saturating amount of ATP produced somewhat larger delta psi and delta pH values, and the delta -muH+attained was about 310mV. By trapping pH indicators in the vesicles during their reconstitution it was found that the pH inside the vesicles was pH 4-5 during ATP hydrolysis. The effects of energy transfer inhibitors, uncouplers, ionophores, and permeant anions on these vesicles were studied.", "contents": "Electrochemical potential of protons in vesicles reconstituted from purified, proton-translocating adenosine triphosphatase. Measurements were made of the difference in the electrochemical potential of protons (delta-mu H+) across the membrane of vesicles restituted from the ATPase complex (TF0.F1) purified from a thermophilic bacterium and P-lipids. Two fluorescent dyes, anilinonaphthalene sulfonate (ANS) and 9-aminoacridine (9AA) were used as probes for measuring the membrane potential (delta psi) and pH difference across the membrane (delta pH), respectively. In the presence of Tris buffer the maximal delta psi ans no delta pH were produced, while in the presence of the permeant anion NO-3 the maximal delta pH and a low delta psi were produced by the addition of ATP. When thATP concentration was 0.24 mm, the delta psi was 140-150 mV (positive inside) in Tris buffer, and the delta pH was 2.9-3.5 units (acidic inside) in the presence of NO-3. Addition of a saturating amount of ATP produced somewhat larger delta psi and delta pH values, and the delta -muH+attained was about 310mV. By trapping pH indicators in the vesicles during their reconstitution it was found that the pH inside the vesicles was pH 4-5 during ATP hydrolysis. The effects of energy transfer inhibitors, uncouplers, ionophores, and permeant anions on these vesicles were studied."}
{"id": "PMID:13222", "title": "Electrical hemolysis of human and bovine red blood cells.", "content": "The external electric field strength required for electrical hemolysis of human red blood cells depends sensitively on the composition of the external medium. In isotonic NaCl und KCl solutions the onset of electrical hemolysis is observed at 4 kV per cm and 50 per cent hemolysis at 6 kV per cm, whereas increasing concentrations of phosphate, sulphate, sucrose, inulin and EDTA shift the onset and the 50 per cent hemolysis-value to higher field strengths. The most pronounced effect is observed for inulin and EDTA. In the presence of these substances the threshold value of the electric field strength is shifted to 14 kV per cm. This is in contrast to the dielectric breakdown voltage of human red blood cells which is unaltered by these substances and was measured  to be approximately 1 V corresponding in the electrolytical discharge chamber to an external electric field strength of 2 to 3 kV per cm. On the other hand, dielectric breakdown of bovine red blood cell membranes occurs in NaCl solution at 4 to 5 kV per cm and is coupled directly with hemoglobin release. The electrical hemolysis of cells of this species is unaffected by the above substances with exception of inulin. Inulin suppressed the electrical hemolysis up to 15 kV per cm. The data can be explained by the assumption that the reflection coefficients of the membranes of these two species to bivalent anions and uncharged molecules are field-dependent to a different extent. This explanation implies that electrical hemolysis is a secondary process of osmotic nature induced by the reversible permeability change of the membrane (dielectric breakdown) in response to an electric field. This view is supported by the observation that the mean volumes of ghost cells obtained by electrical hemolysis can be changed by changing the external phosphate concentration during hemolysis and resealing, or by subjecting the cells to a transient osmotic stress immediately after the electrical hemolysis step. An interesting finding is that the breakdown voltage, although constant throughout each normally distributed ghost size distribution, increases with increasing mean volume of the ghost populations.", "contents": "Electrical hemolysis of human and bovine red blood cells. The external electric field strength required for electrical hemolysis of human red blood cells depends sensitively on the composition of the external medium. In isotonic NaCl und KCl solutions the onset of electrical hemolysis is observed at 4 kV per cm and 50 per cent hemolysis at 6 kV per cm, whereas increasing concentrations of phosphate, sulphate, sucrose, inulin and EDTA shift the onset and the 50 per cent hemolysis-value to higher field strengths. The most pronounced effect is observed for inulin and EDTA. In the presence of these substances the threshold value of the electric field strength is shifted to 14 kV per cm. This is in contrast to the dielectric breakdown voltage of human red blood cells which is unaltered by these substances and was measured  to be approximately 1 V corresponding in the electrolytical discharge chamber to an external electric field strength of 2 to 3 kV per cm. On the other hand, dielectric breakdown of bovine red blood cell membranes occurs in NaCl solution at 4 to 5 kV per cm and is coupled directly with hemoglobin release. The electrical hemolysis of cells of this species is unaffected by the above substances with exception of inulin. Inulin suppressed the electrical hemolysis up to 15 kV per cm. The data can be explained by the assumption that the reflection coefficients of the membranes of these two species to bivalent anions and uncharged molecules are field-dependent to a different extent. This explanation implies that electrical hemolysis is a secondary process of osmotic nature induced by the reversible permeability change of the membrane (dielectric breakdown) in response to an electric field. This view is supported by the observation that the mean volumes of ghost cells obtained by electrical hemolysis can be changed by changing the external phosphate concentration during hemolysis and resealing, or by subjecting the cells to a transient osmotic stress immediately after the electrical hemolysis step. An interesting finding is that the breakdown voltage, although constant throughout each normally distributed ghost size distribution, increases with increasing mean volume of the ghost populations."}
{"id": "PMID:13223", "title": "Effects of parathyroid hormone on H+ and NH+4 excretion in toad urinary bladder.", "content": "The urinary bladder of Bufo marinus excretes H+ and NH+4, and the H+ excretion is increased after the animal is placed in metabolic acidosis. The present study was done to determine if parathyroid hormone could stimulate the bladder to increase the excretion of H+ and/or NH+4. Parathyroid hormone added to the serosal solution in a final concentration of 10 mug/ml was found to increase H+ excretion by 50 per cent above the control hemibladders, while there was no effect on NH+4 excretion. Parathyroid hormone had no effect on H+ excretion when added to the mucosal solution. We also performed experiments utilizing theophylline and dibutyryl cyclic AMP which mimicked those of the parathyroid hormone experiments. A dose-response analysis was performed and the results indicate that 1 mug/ml of parathyroid hormone was the minimal effective dose. These results suggest that parathyroid hormone can stimulate H+ excretion in the toad urinary bladder and this effect seems to be mediated by cyclic AMP. In addition, it was found that parathyroid hormone has no effect on NH+4 excretion.", "contents": "Effects of parathyroid hormone on H+ and NH+4 excretion in toad urinary bladder. The urinary bladder of Bufo marinus excretes H+ and NH+4, and the H+ excretion is increased after the animal is placed in metabolic acidosis. The present study was done to determine if parathyroid hormone could stimulate the bladder to increase the excretion of H+ and/or NH+4. Parathyroid hormone added to the serosal solution in a final concentration of 10 mug/ml was found to increase H+ excretion by 50 per cent above the control hemibladders, while there was no effect on NH+4 excretion. Parathyroid hormone had no effect on H+ excretion when added to the mucosal solution. We also performed experiments utilizing theophylline and dibutyryl cyclic AMP which mimicked those of the parathyroid hormone experiments. A dose-response analysis was performed and the results indicate that 1 mug/ml of parathyroid hormone was the minimal effective dose. These results suggest that parathyroid hormone can stimulate H+ excretion in the toad urinary bladder and this effect seems to be mediated by cyclic AMP. In addition, it was found that parathyroid hormone has no effect on NH+4 excretion."}
{"id": "PMID:13225", "title": "The possible role of solid surface area in condensation reactions during chemical evolution: reevaluation.", "content": "Published data on adsorption and condensation of amino acids, purine and pyrimidine bases, sugars, nucleosides, and nucleotides are analyzed in connection with Bernal's hypothesis that clays and other minerals may have provided the most likely surface for adsorption and condensation of these molecules in prebiotic times. Using surface concentration and reaction rate as the main criteria for the feasibility of condensation reactions, four types of prebiotic environments were analyzed: (1) an ocean-sediment system, (2) a dehydrated lagoon bed produced by evaporation, (3) the surface of a frozen sediment, and (4) a fluctuating system where hydration (rainstorms, tidal variations, flooding) and dehysration (evaporation) take place in a cyclic manner. With the possible exception of nucleotides, low adsorption of organomonomers on sediment surfaces of a prebiotic ocean (pH 8) is expected, and significant condensation is considered unlikely. In dehydrated and frozen systems, high surface concentrations are probable and condensation is more likely. In fluctuating environments, condensation rates will be enhanced and the size distribution of the oligomers formed during dehydration may be influenced by a \"redistribution mechanism\" in which adsorbed oligomers and monomers are desorbed and redistributed on the solid surface during the next hydration-dehydration cycle.", "contents": "The possible role of solid surface area in condensation reactions during chemical evolution: reevaluation. Published data on adsorption and condensation of amino acids, purine and pyrimidine bases, sugars, nucleosides, and nucleotides are analyzed in connection with Bernal's hypothesis that clays and other minerals may have provided the most likely surface for adsorption and condensation of these molecules in prebiotic times. Using surface concentration and reaction rate as the main criteria for the feasibility of condensation reactions, four types of prebiotic environments were analyzed: (1) an ocean-sediment system, (2) a dehydrated lagoon bed produced by evaporation, (3) the surface of a frozen sediment, and (4) a fluctuating system where hydration (rainstorms, tidal variations, flooding) and dehysration (evaporation) take place in a cyclic manner. With the possible exception of nucleotides, low adsorption of organomonomers on sediment surfaces of a prebiotic ocean (pH 8) is expected, and significant condensation is considered unlikely. In dehydrated and frozen systems, high surface concentrations are probable and condensation is more likely. In fluctuating environments, condensation rates will be enhanced and the size distribution of the oligomers formed during dehydration may be influenced by a \"redistribution mechanism\" in which adsorbed oligomers and monomers are desorbed and redistributed on the solid surface during the next hydration-dehydration cycle."}
{"id": "PMID:13226", "title": "Some aspects and implications of coital physiology.", "content": "A review of some experiments in human coital physiology in the home setting considers their possible value to the sex therapist. Blood pressure changes are described in normal subjects with reference to their relevance in patients with heart disease or high blood pressure. Respiratory patterns and intravaginal and intrauterine pressure changes are described during coitus, and their significance in different types of female orgasm are discussed. It now appears that a specific deeply satisfying and terminative female orgasm is associated with a particular type of respiratory pattern and intrauterine pressure change. The use of radiotelemetry devices to measure pressure and pH changes during coitus makes home studies possible. Further projects and areas for future study are considered.", "contents": "Some aspects and implications of coital physiology. A review of some experiments in human coital physiology in the home setting considers their possible value to the sex therapist. Blood pressure changes are described in normal subjects with reference to their relevance in patients with heart disease or high blood pressure. Respiratory patterns and intravaginal and intrauterine pressure changes are described during coitus, and their significance in different types of female orgasm are discussed. It now appears that a specific deeply satisfying and terminative female orgasm is associated with a particular type of respiratory pattern and intrauterine pressure change. The use of radiotelemetry devices to measure pressure and pH changes during coitus makes home studies possible. Further projects and areas for future study are considered."}
{"id": "PMID:13227", "title": "Role of endogenous murine leukemia virus in immunologically triggered lymphoreticular tumors. I. Development and use of oncogenic cellfree preparations serially passaged in vivo.", "content": "Cellfree extracts (CFEs) prepared from (BALB/cJ X A/J)F1 (CAF1) and (BALB/cJ X C57BL/6J)F1 (CB6F1) mice in which a graft-versus-host reaction (GVHR) has been induced are known to be oncogenic, but only after a protracted latent period (mean, 16 mo). Serial passage of such CFEs in successive generations of syngeneic mice inoculated at birth led to the development of two separate oncogenic preparations, the CA serioes in CAF, mice and the CB series in CB6F, mice, in which the mean latent period was reduced to 6 and 12 months, respectively. Both oncogenic preparations contained infectious B-tropic murine leukemia virus (MuLV) and particles with the ultrastructural characteristics of MuLV. No other kind of virus particle was seen. When these preparations were injected into infant syngeneic mice, B-tropic MuLV could be detected in the reticular tissues as early as 2 weeks thereafter. The virus persisted in the reticular tissues and was present in the lymphoreticular tumors that subsequently developed. However, if the same preparation was injected into young adult recipients, there may have been transient MuLV replication, but the virus subsequently disappeared from the reticular tissues and no lymphoreticular tumors developed. Previous experiments showed that MuLV was present in CFEs prepared from CAF, animals with the GVHR but absent in those of normal control mice. Since the lymphoreticular tumors arising in mice with the GVHR were the same as those induced by the CA and CB MuLV preparations, it was concluded that tumorigenesis in mice with the GVHR was caused by endogenous B-tropic MuLV activated by the immunologic disturbance.", "contents": "Role of endogenous murine leukemia virus in immunologically triggered lymphoreticular tumors. I. Development and use of oncogenic cellfree preparations serially passaged in vivo. Cellfree extracts (CFEs) prepared from (BALB/cJ X A/J)F1 (CAF1) and (BALB/cJ X C57BL/6J)F1 (CB6F1) mice in which a graft-versus-host reaction (GVHR) has been induced are known to be oncogenic, but only after a protracted latent period (mean, 16 mo). Serial passage of such CFEs in successive generations of syngeneic mice inoculated at birth led to the development of two separate oncogenic preparations, the CA serioes in CAF, mice and the CB series in CB6F, mice, in which the mean latent period was reduced to 6 and 12 months, respectively. Both oncogenic preparations contained infectious B-tropic murine leukemia virus (MuLV) and particles with the ultrastructural characteristics of MuLV. No other kind of virus particle was seen. When these preparations were injected into infant syngeneic mice, B-tropic MuLV could be detected in the reticular tissues as early as 2 weeks thereafter. The virus persisted in the reticular tissues and was present in the lymphoreticular tumors that subsequently developed. However, if the same preparation was injected into young adult recipients, there may have been transient MuLV replication, but the virus subsequently disappeared from the reticular tissues and no lymphoreticular tumors developed. Previous experiments showed that MuLV was present in CFEs prepared from CAF, animals with the GVHR but absent in those of normal control mice. Since the lymphoreticular tumors arising in mice with the GVHR were the same as those induced by the CA and CB MuLV preparations, it was concluded that tumorigenesis in mice with the GVHR was caused by endogenous B-tropic MuLV activated by the immunologic disturbance."}
{"id": "PMID:13228", "title": "Neurotransmission and glial cells: a functional relationship?", "content": "The investigations reported here demonstrate high affinity transport systems localized in glial cells which appear to be specific for amino acid neurotransmitter candidates. Data on uptake of gamma-aminobutyric acid (GABA), glutamate, glycine, and taurine, show transport systems with KT'S in the range of 10(-5) M. In addition, the distribution of the glial transport system for glycine is shown to parallel the presumed distribution of glycine as an inhibitory neurotransmitter. Results of these studies also suggest that transport studies on brain homogenates or synaptosomal preparations do not serve to localize these functions to synaptic elements as is widely believed. This report shows that glia can form vesicles during homogenization which band which synaptosomes in density gradients, and retain transport activity. Glia also may contribute to the release of neurotransmitters via control of the extracellular Ca++ concentration. This is shown by the ability of GABA in the extracellular media to cause release of Ca++ by glia.", "contents": "Neurotransmission and glial cells: a functional relationship? The investigations reported here demonstrate high affinity transport systems localized in glial cells which appear to be specific for amino acid neurotransmitter candidates. Data on uptake of gamma-aminobutyric acid (GABA), glutamate, glycine, and taurine, show transport systems with KT'S in the range of 10(-5) M. In addition, the distribution of the glial transport system for glycine is shown to parallel the presumed distribution of glycine as an inhibitory neurotransmitter. Results of these studies also suggest that transport studies on brain homogenates or synaptosomal preparations do not serve to localize these functions to synaptic elements as is widely believed. This report shows that glia can form vesicles during homogenization which band which synaptosomes in density gradients, and retain transport activity. Glia also may contribute to the release of neurotransmitters via control of the extracellular Ca++ concentration. This is shown by the ability of GABA in the extracellular media to cause release of Ca++ by glia."}
{"id": "PMID:13229", "title": "Role of the pneumococcal autolysin (murein hydrolase) in the release of progeny bacteriophage and in the bacteriophage-induced lysis of the host cells.", "content": "The pneumococcal bacteriophage Dp-1 seems to require the activity of the N-acetylmuramic acid-L-alanine amidase of the host bacterium for the liberation of phage progeny into the medium. This conclusion is based on a series of observations indicating that the exit of progeny phage particles is prevented by conditions that specifically inhibit the activity of the pneumococcal autolysin. These inhibitory conditions are as follows: (i) growth of the bacteria on ethanolamine-containing medium; (ii) growth of the cells at pH values that inhibit penicillin-induced lysis of pneumococcal cultures and lysis in the stationary phase of growth; (iii) addition of trypsin or the autolysin-inhibitory pneumococcal Forssman antigen (lipoteichoric acid) to the growth medium before lysis; (iv) infection of an autolysin-defective pneumococcal mutant at a multiplicity of infection less than 10 (treatment of such infected mutant bacteria with wild-type autolysin from without can liberate the entrapped progeny phage particles); (v) release of phage particles and culture lysis can also be inhibited by the addition of chloramphenicol to infected cultures just before the time at which lysis would normally occur. Bacteria infected with Dp-1 under conditions nonpermissive for culture lysis and phage release secrete into the growth medium a substantial portion of their cellular Forssman antigen in the form of a macromolecular complex that has autolysin-inhibitory activity. We suggest that a phage product may trigger the bacterial autolysin by a mechanism similar to that operating during treatment of pneumococci with penicillin (Tomasz and Waks, 1975).", "contents": "Role of the pneumococcal autolysin (murein hydrolase) in the release of progeny bacteriophage and in the bacteriophage-induced lysis of the host cells. The pneumococcal bacteriophage Dp-1 seems to require the activity of the N-acetylmuramic acid-L-alanine amidase of the host bacterium for the liberation of phage progeny into the medium. This conclusion is based on a series of observations indicating that the exit of progeny phage particles is prevented by conditions that specifically inhibit the activity of the pneumococcal autolysin. These inhibitory conditions are as follows: (i) growth of the bacteria on ethanolamine-containing medium; (ii) growth of the cells at pH values that inhibit penicillin-induced lysis of pneumococcal cultures and lysis in the stationary phase of growth; (iii) addition of trypsin or the autolysin-inhibitory pneumococcal Forssman antigen (lipoteichoric acid) to the growth medium before lysis; (iv) infection of an autolysin-defective pneumococcal mutant at a multiplicity of infection less than 10 (treatment of such infected mutant bacteria with wild-type autolysin from without can liberate the entrapped progeny phage particles); (v) release of phage particles and culture lysis can also be inhibited by the addition of chloramphenicol to infected cultures just before the time at which lysis would normally occur. Bacteria infected with Dp-1 under conditions nonpermissive for culture lysis and phage release secrete into the growth medium a substantial portion of their cellular Forssman antigen in the form of a macromolecular complex that has autolysin-inhibitory activity. We suggest that a phage product may trigger the bacterial autolysin by a mechanism similar to that operating during treatment of pneumococci with penicillin (Tomasz and Waks, 1975)."}
{"id": "PMID:13230", "title": "Prazosin-new hypertensive agent. A double-blind crossover study in the treatment of hypertension.", "content": "Prazosin hydrochloride, a new antihypertensive agent, is said to be of mild-to-moderate potency when used as a sole agent in mild-to-moderate hypertension and when used in conjunction with other agents in severe hypertension. In our study of 14 patients comparing hydrochlorothiazide with prazosin, the antigypertensive effect of prazosin was less than that of hydrochlorothiazide. The greatest application of prazosin may be in conjunction with thiazide diuretics and beta-adrenergic blocking agents as the second or third drug.", "contents": "Prazosin-new hypertensive agent. A double-blind crossover study in the treatment of hypertension. Prazosin hydrochloride, a new antihypertensive agent, is said to be of mild-to-moderate potency when used as a sole agent in mild-to-moderate hypertension and when used in conjunction with other agents in severe hypertension. In our study of 14 patients comparing hydrochlorothiazide with prazosin, the antigypertensive effect of prazosin was less than that of hydrochlorothiazide. The greatest application of prazosin may be in conjunction with thiazide diuretics and beta-adrenergic blocking agents as the second or third drug."}
{"id": "PMID:13231", "title": "Hemodialysis in methyprylon overdose. Some pharmacokinetic considerations.", "content": "Serial measurements of serum methyprylon concentration were made in the case of a 14-year-old girl who ingested an overdose of the drug. Our data indicate that, in the presence of high plasma levels of the drug, much longer half-lives than the usually reported four hours may be observed. It is postulated that saturation kinetics may be a possible mechanism for this observation. The striking clinical improvement after six hours of hemodialysis demonstrated the efficacy of this mode of treatment in our patient.", "contents": "Hemodialysis in methyprylon overdose. Some pharmacokinetic considerations. Serial measurements of serum methyprylon concentration were made in the case of a 14-year-old girl who ingested an overdose of the drug. Our data indicate that, in the presence of high plasma levels of the drug, much longer half-lives than the usually reported four hours may be observed. It is postulated that saturation kinetics may be a possible mechanism for this observation. The striking clinical improvement after six hours of hemodialysis demonstrated the efficacy of this mode of treatment in our patient."}
{"id": "PMID:13234", "title": "Effects of subcutaneously administered adrenaline on human eccrine sweating, with special reference to the physiological significance of the adrenergic sweating mechanism.", "content": "The effects of a small dose (3-6 mug/kg) of subcutaneously administered adrenaline on thermal sweating were studied while subjects were at rest and during or after excerise by means of continuous monitoring by resistance hygrometry of the sweat rate in the forearm area. In most cases, the sweat rate either decreased or did not change significantly following the adrenaline injection, however, among athletic subjects it showed a mild increase in a few cases, mostly during or after exercise. In the area receiving the intradermal injection of an alpha-adrenergic blocking agent, tolazoline, phentolamine or dihydroergotoxine, subcutaneous adrenaline consistently caused an increase in sweat rate. Adrenaline (15 mug) was injected intravenously with similar results. Noradrenaline was used in place of adrenaline in some cases, and the results were essentially the same as, but less distinct than, those with adrenaline. The results indicate that a small dose of subcutaneous adrenaline has dual effects, with the sweat-inhibitory effect generally predominating over the sweat-facilitatory one, with occasional exceptions in association with exercise and/or physical training. The former effect is largely secondary to its vasconstrictive effect, whereas the latter appears to be secondary to its systemic effects, such as central and calorigenic ones. It is concluded that adrenaline within a physiological range exerts no direct action on human eccrine sweat glands.", "contents": "Effects of subcutaneously administered adrenaline on human eccrine sweating, with special reference to the physiological significance of the adrenergic sweating mechanism. The effects of a small dose (3-6 mug/kg) of subcutaneously administered adrenaline on thermal sweating were studied while subjects were at rest and during or after excerise by means of continuous monitoring by resistance hygrometry of the sweat rate in the forearm area. In most cases, the sweat rate either decreased or did not change significantly following the adrenaline injection, however, among athletic subjects it showed a mild increase in a few cases, mostly during or after exercise. In the area receiving the intradermal injection of an alpha-adrenergic blocking agent, tolazoline, phentolamine or dihydroergotoxine, subcutaneous adrenaline consistently caused an increase in sweat rate. Adrenaline (15 mug) was injected intravenously with similar results. Noradrenaline was used in place of adrenaline in some cases, and the results were essentially the same as, but less distinct than, those with adrenaline. The results indicate that a small dose of subcutaneous adrenaline has dual effects, with the sweat-inhibitory effect generally predominating over the sweat-facilitatory one, with occasional exceptions in association with exercise and/or physical training. The former effect is largely secondary to its vasconstrictive effect, whereas the latter appears to be secondary to its systemic effects, such as central and calorigenic ones. It is concluded that adrenaline within a physiological range exerts no direct action on human eccrine sweat glands."}
{"id": "PMID:13235", "title": "Jimson seed poisoning-- a new hallucinogen on the horizon.", "content": "Of 27 patients with Jimson seed poisoning recently treated in the University of Cincinnati Medical Center, 15 were admitted to the hospital, while 12 were treated and released. The patients ranged in age from 13 to 21. The dose was between 2 gm and 25 gm. Time from ingestion to arrival in the emergency department averaged 12.1 hours for those admitted and 10 hours for those who were not. All patients had altered mental status. Twenty-five of the 27 received Ipecac and all but one received at least 2 mg of physostigmine, which produced dramatic improvement in central nervous system symptoms. The authors have developed a management protocol based on physiologic criteria.", "contents": "Jimson seed poisoning-- a new hallucinogen on the horizon. Of 27 patients with Jimson seed poisoning recently treated in the University of Cincinnati Medical Center, 15 were admitted to the hospital, while 12 were treated and released. The patients ranged in age from 13 to 21. The dose was between 2 gm and 25 gm. Time from ingestion to arrival in the emergency department averaged 12.1 hours for those admitted and 10 hours for those who were not. All patients had altered mental status. Twenty-five of the 27 received Ipecac and all but one received at least 2 mg of physostigmine, which produced dramatic improvement in central nervous system symptoms. The authors have developed a management protocol based on physiologic criteria."}
{"id": "PMID:13236", "title": "[Use of beta-stimulators in chronic ischemic heart disease with complete atrioventricular block complicated by congestive circulatory insufficiency].", "content": "In 23 patients with full atrioventricular block and congestive heart failure developing against the background of chronic ischaemic heart disease Isuprel was injected intravenously at a speed of 1 to 3 muG/min. A positive chronotropic effect of the drug was observed and attributed to the dose employed. Isuprel produced a positive dynamics in the structure of the cardiac cycle in the treated patients. A course of such therapy resulted in a reduction, or even disappearance of the circulatory insufficiency signs in the majority of patients, but sinus rhythm could not be restored in either of them. The noted side effects were typical of beta-stimulators. Two patients developed anginal pains in the zone of the heart when the drug was given intravenously.", "contents": "[Use of beta-stimulators in chronic ischemic heart disease with complete atrioventricular block complicated by congestive circulatory insufficiency]. In 23 patients with full atrioventricular block and congestive heart failure developing against the background of chronic ischaemic heart disease Isuprel was injected intravenously at a speed of 1 to 3 muG/min. A positive chronotropic effect of the drug was observed and attributed to the dose employed. Isuprel produced a positive dynamics in the structure of the cardiac cycle in the treated patients. A course of such therapy resulted in a reduction, or even disappearance of the circulatory insufficiency signs in the majority of patients, but sinus rhythm could not be restored in either of them. The noted side effects were typical of beta-stimulators. Two patients developed anginal pains in the zone of the heart when the drug was given intravenously."}
{"id": "PMID:13237", "title": "Isolation and characterization of uricine from uric acid stones.", "content": "Uricine was found to be present in all uric acid stones tested, although another physiochemically related pigment was occasionally present. Uricine is of low molecular weight (28.2) and a preliminary analysis of its structure suggests that it is formed by two pyrrolic rings. It is a yellow pigment whose color is pH-dependent, shifting from reddish-yellow to green at pH 1.0. It is water soluble, but its solubility increases in alkaline solutions. Preliminary evidence suggests that uricine is related metabolically to bilirubin-like compounds.", "contents": "Isolation and characterization of uricine from uric acid stones. Uricine was found to be present in all uric acid stones tested, although another physiochemically related pigment was occasionally present. Uricine is of low molecular weight (28.2) and a preliminary analysis of its structure suggests that it is formed by two pyrrolic rings. It is a yellow pigment whose color is pH-dependent, shifting from reddish-yellow to green at pH 1.0. It is water soluble, but its solubility increases in alkaline solutions. Preliminary evidence suggests that uricine is related metabolically to bilirubin-like compounds."}
{"id": "PMID:13240", "title": "[The influence of plasma protein binding on distribution and pharmacological activity of tranquilizers of the benzodiazepine group (author's transl)].", "content": "This paper discusses the problem if the plasma protein binding of benzodiazepine derivatives can influence distribution and pharmacological activity of the drugs. The distribution of the benzodiazepines in the organism is influenced not only by the plasma protein binding of the drugs, but also by several other factors, especially since the drugs are mostly lipophilic. Thus, an effect of the plasma protein binding on the distribution can only be expected if the benzodiazepine derivative is highly bound to the plasma proteins. Thus results have been shown only for diazepam and chlordiazepoxid, which indicate an effect of the plasma protein binding on distribution and pharmacological activity, for example the existence of a direct correlation between unwanted CNS depressions and low plasma albumin concentrations and a direct correlation between the plasma protein binding and the biological half-life. There are no observations available on a displacement of other drugs from their binding to plasma proteins by benzodiazepines. The observed displacement of thyroid hormones from their binding to plasma proteins seems to have only a significance for thyroid function tests in vitro. It was shown that benzodiazepines decrease the amount of L-tryptophan bound to serum albumin in vitro and in vivo and increased therewith the L-tryptophan concentration in the brain. At present it can not be confirmed if these observations bear any significance on the pharmacological activity of the drugs. But these experiments demonstrate the significance of the use of albumin as a model for the interaction of drugs with tissue or receptorproteins.", "contents": "[The influence of plasma protein binding on distribution and pharmacological activity of tranquilizers of the benzodiazepine group (author's transl)]. This paper discusses the problem if the plasma protein binding of benzodiazepine derivatives can influence distribution and pharmacological activity of the drugs. The distribution of the benzodiazepines in the organism is influenced not only by the plasma protein binding of the drugs, but also by several other factors, especially since the drugs are mostly lipophilic. Thus, an effect of the plasma protein binding on the distribution can only be expected if the benzodiazepine derivative is highly bound to the plasma proteins. Thus results have been shown only for diazepam and chlordiazepoxid, which indicate an effect of the plasma protein binding on distribution and pharmacological activity, for example the existence of a direct correlation between unwanted CNS depressions and low plasma albumin concentrations and a direct correlation between the plasma protein binding and the biological half-life. There are no observations available on a displacement of other drugs from their binding to plasma proteins by benzodiazepines. The observed displacement of thyroid hormones from their binding to plasma proteins seems to have only a significance for thyroid function tests in vitro. It was shown that benzodiazepines decrease the amount of L-tryptophan bound to serum albumin in vitro and in vivo and increased therewith the L-tryptophan concentration in the brain. At present it can not be confirmed if these observations bear any significance on the pharmacological activity of the drugs. But these experiments demonstrate the significance of the use of albumin as a model for the interaction of drugs with tissue or receptorproteins."}
{"id": "PMID:13248", "title": "Reoperations for myocardial revascularization.", "content": "Reoperations solely for myocardial revascularization were performed in 219 consecutive patients (1967 to 1975). Indications were (1) graft failure, 46 (21 per cent); (2) progressive atherosclerosis, 42 (19 per cent); (3) incomplete revascularization, 39 (18 per cent); and (4) combinations, 92 (42 per cent). Primary operations included bypass grafts in 100 patients; mammary artery implants, 87; and combinations of direct and indirect procedures, 32. Reoperations performed were single bypass, 141 patients; double, 61; and triple or other coronary artery operations, 17. Eight patients died within 30 days of operation (3.7 per cent). Major postoperative complications included hepatitis, 24 (11 per cent); myocardial infarction, 19 (9 per cent); bleeding, 21 (10 per cent); and respiratory insufficiency, 12 (5 per cent). Follow-up for 202 long-term survivors was complete (mean 29 months). In patients who originally underwent direct revascularization, Class I or II (N.Y.H.A.) was attained in 35 of 43 (81 per cent) of those reoperated upon for primary graft failure, in 14 of 15 (93 per cent) of those with progressive atherosclerosis, and in 27 of 33 (82 per cent) of patients with combined indications. Arteriography was performed after the reoperation in 55 patients (mean interval 17 months), and 65 of 77 (84 per cent) grafts were patent. Nineteen of 22 grafts performed for primary graft failure were patent. We have made the following conclusions: (1) Reoperation for direct myocardial revascularization can be accomplished with low mortality rates although morbidity is high; (2) complete relief of symptoms was achieved in 65 per cent of survivors; (3) results in patients reoperated upon for graft failure alone were similar to results in those operated upon for progressive atherosclerosis or combined indications; and (4) high graft patency was found in secondary grafts constructed to arteries involved with primary graft failure.", "contents": "Reoperations for myocardial revascularization. Reoperations solely for myocardial revascularization were performed in 219 consecutive patients (1967 to 1975). Indications were (1) graft failure, 46 (21 per cent); (2) progressive atherosclerosis, 42 (19 per cent); (3) incomplete revascularization, 39 (18 per cent); and (4) combinations, 92 (42 per cent). Primary operations included bypass grafts in 100 patients; mammary artery implants, 87; and combinations of direct and indirect procedures, 32. Reoperations performed were single bypass, 141 patients; double, 61; and triple or other coronary artery operations, 17. Eight patients died within 30 days of operation (3.7 per cent). Major postoperative complications included hepatitis, 24 (11 per cent); myocardial infarction, 19 (9 per cent); bleeding, 21 (10 per cent); and respiratory insufficiency, 12 (5 per cent). Follow-up for 202 long-term survivors was complete (mean 29 months). In patients who originally underwent direct revascularization, Class I or II (N.Y.H.A.) was attained in 35 of 43 (81 per cent) of those reoperated upon for primary graft failure, in 14 of 15 (93 per cent) of those with progressive atherosclerosis, and in 27 of 33 (82 per cent) of patients with combined indications. Arteriography was performed after the reoperation in 55 patients (mean interval 17 months), and 65 of 77 (84 per cent) grafts were patent. Nineteen of 22 grafts performed for primary graft failure were patent. We have made the following conclusions: (1) Reoperation for direct myocardial revascularization can be accomplished with low mortality rates although morbidity is high; (2) complete relief of symptoms was achieved in 65 per cent of survivors; (3) results in patients reoperated upon for graft failure alone were similar to results in those operated upon for progressive atherosclerosis or combined indications; and (4) high graft patency was found in secondary grafts constructed to arteries involved with primary graft failure."}
{"id": "PMID:13244", "title": "[Relationship of the content of carboxyhemoglobin in the blood and of carbon monoxide in the expired air of test subjects to the CO concentration in the air of a hermetic chamber].", "content": "Four manned experiments (4 test subjects participating in each) were carried out in a chamber of 24 m3. The effect of CO at a concentration of 10 to 45 mg/m3 on the content of carboxyhemoglobin in the blood, nonhemoglobin iron in the plasma, CO in the breathing air, catalase and peroxidase activity was studied. A correlation was found between these parameters and CO concentration in the atmosphere and exposure time. It was demonstrated that a continuous exposure (up to 90 days) to CO at a concentration of 10 mg/m3 under favorable microclimatic conditions produced no significant effect on the above mentioned biochemical paramters.", "contents": "[Relationship of the content of carboxyhemoglobin in the blood and of carbon monoxide in the expired air of test subjects to the CO concentration in the air of a hermetic chamber]. Four manned experiments (4 test subjects participating in each) were carried out in a chamber of 24 m3. The effect of CO at a concentration of 10 to 45 mg/m3 on the content of carboxyhemoglobin in the blood, nonhemoglobin iron in the plasma, CO in the breathing air, catalase and peroxidase activity was studied. A correlation was found between these parameters and CO concentration in the atmosphere and exposure time. It was demonstrated that a continuous exposure (up to 90 days) to CO at a concentration of 10 mg/m3 under favorable microclimatic conditions produced no significant effect on the above mentioned biochemical paramters."}
{"id": "PMID:13246", "title": "[Study of the possibility of utilizing the transpired mositure condensate from sweet potato for growing plants in biological life support systems].", "content": "The effect of nonpurified condensate obtained during prolonged cultivation of batata in a sealed chamber upon batata cuttings and seedlings of garden cress, radish and Chinese cabbage was studied. It was shown that nonpurified condensate produced an inhibitory effect on the formation of roots in batata cuttings and on the growth of previously developed roots of batata cuttings and seedlings. The studies which used a chemical model of 3,4-dihydroxy phenylalanine indicated that the condensate contained biologically active substance of organic origin. However, only experiments with the real continuous culture of batata, using real dilutions of the condensate that depend on the size of the greenhouse and the amount of the nutrient solution would clarify wheather condensate of transpiration water of batata plants can be repeatedly utilized in life support systems.", "contents": "[Study of the possibility of utilizing the transpired mositure condensate from sweet potato for growing plants in biological life support systems]. The effect of nonpurified condensate obtained during prolonged cultivation of batata in a sealed chamber upon batata cuttings and seedlings of garden cress, radish and Chinese cabbage was studied. It was shown that nonpurified condensate produced an inhibitory effect on the formation of roots in batata cuttings and on the growth of previously developed roots of batata cuttings and seedlings. The studies which used a chemical model of 3,4-dihydroxy phenylalanine indicated that the condensate contained biologically active substance of organic origin. However, only experiments with the real continuous culture of batata, using real dilutions of the condensate that depend on the size of the greenhouse and the amount of the nutrient solution would clarify wheather condensate of transpiration water of batata plants can be repeatedly utilized in life support systems."}
{"id": "PMID:13247", "title": "[Hygienic evaluation of experimental samples of antimicrobial underwear containing hexachlorophene].", "content": "The hygienic examination of 12 samples of knitted underwear which contained hexachlorophene added during fiber formation allowed the selection of four types that can be used under poor sanitation conditions. Taking into consideration possible changes in the proportion of various micoorganisms during prolonged space flights, it is recommended to carry out a complex investigation in order to allow the use of the antimicrobial underwear by specific crewmembers during a certain period of time.", "contents": "[Hygienic evaluation of experimental samples of antimicrobial underwear containing hexachlorophene]. The hygienic examination of 12 samples of knitted underwear which contained hexachlorophene added during fiber formation allowed the selection of four types that can be used under poor sanitation conditions. Taking into consideration possible changes in the proportion of various micoorganisms during prolonged space flights, it is recommended to carry out a complex investigation in order to allow the use of the antimicrobial underwear by specific crewmembers during a certain period of time."}
{"id": "PMID:13245", "title": "[Assessment of the quality of relcaimed water by total organic carbon].", "content": "The paper discusses possible application of the method of measuring the total content of organic carbon to evaluate the quality or reclaimed water. The paper gives data on the content of organic carbon, ratio of chemical consumption of oxygen and carbon in the atmospheric condensate, urine, condensate of urine low-temperature evaporation and portable water reclaimed from these sources.", "contents": "[Assessment of the quality of relcaimed water by total organic carbon]. The paper discusses possible application of the method of measuring the total content of organic carbon to evaluate the quality or reclaimed water. The paper gives data on the content of organic carbon, ratio of chemical consumption of oxygen and carbon in the atmospheric condensate, urine, condensate of urine low-temperature evaporation and portable water reclaimed from these sources."}
{"id": "PMID:13249", "title": "A multiple-parameter comparison of immunocompetence and tumor resistance in aged BALB/c mice.", "content": "Several parameters of cell-mediated and humoral immunity were measured in young-adult and aged BALB/c mice and compared with resistance to the ascites form of intraperitoneal induced P815 mastocytoma. It was found that the age-related decline of in vitro phytohemagglutinin (PHA) responsiveness by spleen cells approximated the marked decrease of old mice to tumor-cell challenge and approached that characteristically seen in humoral immunity. Thus, decreased PHA responsiveness of splenic lymphocytes provided as sensitive an estimate of the age-related decline of immunocompetence in old mice as other classical parameters of cell-mediated immunity (e.g. graft-vs-host reaction or in vivo cellular proliferation of parental spleen cells in lethally-irradiated F1 recipients). Results could be interpreted to represent a decreased ability of noncycling T-cells to be released to a functional cycling state.", "contents": "A multiple-parameter comparison of immunocompetence and tumor resistance in aged BALB/c mice. Several parameters of cell-mediated and humoral immunity were measured in young-adult and aged BALB/c mice and compared with resistance to the ascites form of intraperitoneal induced P815 mastocytoma. It was found that the age-related decline of in vitro phytohemagglutinin (PHA) responsiveness by spleen cells approximated the marked decrease of old mice to tumor-cell challenge and approached that characteristically seen in humoral immunity. Thus, decreased PHA responsiveness of splenic lymphocytes provided as sensitive an estimate of the age-related decline of immunocompetence in old mice as other classical parameters of cell-mediated immunity (e.g. graft-vs-host reaction or in vivo cellular proliferation of parental spleen cells in lethally-irradiated F1 recipients). Results could be interpreted to represent a decreased ability of noncycling T-cells to be released to a functional cycling state."}
{"id": "PMID:13260", "title": "Hyperlipoproteinemia, diabetes, and oxygen affinity of hemoglobin.", "content": "Oxyhemoglobin dissociation curves (ODC) were performed on blood from diabetic and nondiabetic subjects with and without hypertriglyceridemia. P50 at in vivo pH was slightly lower than normal in normolipemic diabetics (25.7 versus 26.6 mmHg, p less than 0.05), in spite of increased red cell 2,3-diphosphoglycerate concentration (15.4 versus 14.4 mumole/g Hg, p less than 0.025). P50 at in vivo pH in diabetics with moderately elevated very low density lipoproteins (VLDL)--Type IV hyperlipoproteinemia (HLP)--was likewise found to be slightly lower than normal (25.5 versus 26.6 mmHg, p less than 0.05). In contrast, diabetics with pronounced hyperlipemia due to accumulation of chylomicrons (type I HLP) or due to accumulation of chylomicrons (type I HLP) or due to accumulation of chylomicrons as well as VLDL (type V HLP) showed markedly increased hemoglobin--oxygen affinity (P50:21.1 versus 26.6 mmHg, p less than 0.001). The change in the ODC of normolipemic diabetics is considered to be an expresssion of the presence of an increased proportion of a hemoglobin fraction (Hb Alc) with increased oxygen affinity. The additional change in the ODC of the hyperlipemic patients is thought to be secondary to accumulation of triglyceride-rich particles for the following reasons: (1) a similar increase in oxygen affinity of hemoglobin was demonstrated in familial type I HLP of nondiabetic subjects; (2) normal red cells increased their oxygen affinity when incubated in lactescent plasma; (3) in both acquired types I and V HLP the disappearance of HLP was followed by a normalization of the ODC.", "contents": "Hyperlipoproteinemia, diabetes, and oxygen affinity of hemoglobin. Oxyhemoglobin dissociation curves (ODC) were performed on blood from diabetic and nondiabetic subjects with and without hypertriglyceridemia. P50 at in vivo pH was slightly lower than normal in normolipemic diabetics (25.7 versus 26.6 mmHg, p less than 0.05), in spite of increased red cell 2,3-diphosphoglycerate concentration (15.4 versus 14.4 mumole/g Hg, p less than 0.025). P50 at in vivo pH in diabetics with moderately elevated very low density lipoproteins (VLDL)--Type IV hyperlipoproteinemia (HLP)--was likewise found to be slightly lower than normal (25.5 versus 26.6 mmHg, p less than 0.05). In contrast, diabetics with pronounced hyperlipemia due to accumulation of chylomicrons (type I HLP) or due to accumulation of chylomicrons (type I HLP) or due to accumulation of chylomicrons as well as VLDL (type V HLP) showed markedly increased hemoglobin--oxygen affinity (P50:21.1 versus 26.6 mmHg, p less than 0.001). The change in the ODC of normolipemic diabetics is considered to be an expresssion of the presence of an increased proportion of a hemoglobin fraction (Hb Alc) with increased oxygen affinity. The additional change in the ODC of the hyperlipemic patients is thought to be secondary to accumulation of triglyceride-rich particles for the following reasons: (1) a similar increase in oxygen affinity of hemoglobin was demonstrated in familial type I HLP of nondiabetic subjects; (2) normal red cells increased their oxygen affinity when incubated in lactescent plasma; (3) in both acquired types I and V HLP the disappearance of HLP was followed by a normalization of the ODC."}
{"id": "PMID:13261", "title": "Effects on the diet on brain neurotransmitters.", "content": "The synthesis of neurotransmitters in mammalian brain responds rapidly to changes in precursor availability. Serotonin synthesis depends largely on the brain concentrations of L-tryptophan, its precursor amino aicd. This relationship appears to be physiologic: when brain tryptophan levels vary because of insulin secretion or meal ingestion, corresponding alterations occur in the rate of serotonin formation. The ability of any food to modify brain tryptophan (and serotonin) depends on how its ingestion changes the serum concentration of not only tryptophan, but also several other large neutral amino acids that compete with tryptophan for uptake into the brain. Such precursor-induced changes in brain serotonin appear to be functionally important: animals having a reduced level of brain serotonin (caused by the chronic ingestion of a naturally tryptophan-poor diet, such as corn) demonstrate a heightened sensitivity to painful stimuli; this pain sensitivity can be acutely restored to normal values by a single injection of L-tryptophan, which rapidly elevates brain serotonin. The synthesis of catecholamines (e.g., dopamine, norepinephrine) in the brain also varies with the availability of the precursor amino acid L-tyrosine. Single injections of this amino acid increase brain tyrosine levels and accelerate brain catechol synthesis, while injections of a competing neutral amino acid (e.g., leucine, tryptophan) reduce brain tyrosine and its rate of conversion to dopa. The rate of catecholamine synthesis, however, appears to be influenced less by precursor levels than is serotonin formation: tyrosine hydroxylase, whcih catalyzes the rate-limiting step in catecholamine synthesis, responds strongly to end-product inhibition and to other controls that reflect variations in neuronal activity. The synthesis of acetylcholine in brain responds to substrate (choline) availability much like serotonin synthesis. Short-term alterations in brain choline levels are mirrored by similar changes in brain acetylcholine concentration. Variations in the daily dietary intake of choline also modify brain choline and acetylcholine. The relationship between choline availability and acetylchyoline synthesis has already foudn a cletween choline availability and acetylchyoline synthesis has already found a clinical application: choline has been used successfully in the treatment of tardive dyskinesia, a disorder of the central nervous system thought to reflect a deficiency in cholinergic transmission. These relationships between precursor availability from the periphery and brain neurotransmitter synthesis may ultimately provide the brain with information about peripheral metabolic state.", "contents": "Effects on the diet on brain neurotransmitters. The synthesis of neurotransmitters in mammalian brain responds rapidly to changes in precursor availability. Serotonin synthesis depends largely on the brain concentrations of L-tryptophan, its precursor amino aicd. This relationship appears to be physiologic: when brain tryptophan levels vary because of insulin secretion or meal ingestion, corresponding alterations occur in the rate of serotonin formation. The ability of any food to modify brain tryptophan (and serotonin) depends on how its ingestion changes the serum concentration of not only tryptophan, but also several other large neutral amino acids that compete with tryptophan for uptake into the brain. Such precursor-induced changes in brain serotonin appear to be functionally important: animals having a reduced level of brain serotonin (caused by the chronic ingestion of a naturally tryptophan-poor diet, such as corn) demonstrate a heightened sensitivity to painful stimuli; this pain sensitivity can be acutely restored to normal values by a single injection of L-tryptophan, which rapidly elevates brain serotonin. The synthesis of catecholamines (e.g., dopamine, norepinephrine) in the brain also varies with the availability of the precursor amino acid L-tyrosine. Single injections of this amino acid increase brain tyrosine levels and accelerate brain catechol synthesis, while injections of a competing neutral amino acid (e.g., leucine, tryptophan) reduce brain tyrosine and its rate of conversion to dopa. The rate of catecholamine synthesis, however, appears to be influenced less by precursor levels than is serotonin formation: tyrosine hydroxylase, whcih catalyzes the rate-limiting step in catecholamine synthesis, responds strongly to end-product inhibition and to other controls that reflect variations in neuronal activity. The synthesis of acetylcholine in brain responds to substrate (choline) availability much like serotonin synthesis. Short-term alterations in brain choline levels are mirrored by similar changes in brain acetylcholine concentration. Variations in the daily dietary intake of choline also modify brain choline and acetylcholine. The relationship between choline availability and acetylchyoline synthesis has already foudn a cletween choline availability and acetylchyoline synthesis has already found a clinical application: choline has been used successfully in the treatment of tardive dyskinesia, a disorder of the central nervous system thought to reflect a deficiency in cholinergic transmission. These relationships between precursor availability from the periphery and brain neurotransmitter synthesis may ultimately provide the brain with information about peripheral metabolic state."}
{"id": "PMID:13262", "title": "Heritable catabolic and anabolic disorders of lipid metabolism.", "content": "The principal manifestations and metabolic defects in ten heritable disorders of lipid metabolism are discussed. Facile procedures have been developed for the diagnosis of patients with these conditions, the identification of heterozygous carriers, and the prenatal detection of any of these diseases. Enzyme replacement appears promising for patients with Fabry's disease and Gaucher's disease who do not have central nervous system damage. The clinical and biochemical abnormalities that occur in patients with a novel inherited disorder of ganglioside anabolism are described.", "contents": "Heritable catabolic and anabolic disorders of lipid metabolism. The principal manifestations and metabolic defects in ten heritable disorders of lipid metabolism are discussed. Facile procedures have been developed for the diagnosis of patients with these conditions, the identification of heterozygous carriers, and the prenatal detection of any of these diseases. Enzyme replacement appears promising for patients with Fabry's disease and Gaucher's disease who do not have central nervous system damage. The clinical and biochemical abnormalities that occur in patients with a novel inherited disorder of ganglioside anabolism are described."}
{"id": "PMID:13273", "title": "[Transitional state of Candida utilis chemostat culture after shock caused by a low pH value of the medium during 1 generation].", "content": "Transitional states of Candida utilis BKM Y-1668 were found during its growth in conditions of chemostat at D of 0.1 hr(-1) and glycerol limit after a shock caused by an extreme pH value (2.2). The optical density of the cells, the amount of dry biomass and protein, the activity of respiration, the content of ATP, and the activity of ATPase decreased, the character of the decrease being that of damped oscillations. Qualitative changes were detected in the activity of respiration, oxygen uptake was not inhibited by cyanide. More glycerol and phosphorus are utilized in processes of vital activity. Therefore, a sharp change of pH values causes profound changes in the metabolism of the yeast cell.", "contents": "[Transitional state of Candida utilis chemostat culture after shock caused by a low pH value of the medium during 1 generation]. Transitional states of Candida utilis BKM Y-1668 were found during its growth in conditions of chemostat at D of 0.1 hr(-1) and glycerol limit after a shock caused by an extreme pH value (2.2). The optical density of the cells, the amount of dry biomass and protein, the activity of respiration, the content of ATP, and the activity of ATPase decreased, the character of the decrease being that of damped oscillations. Qualitative changes were detected in the activity of respiration, oxygen uptake was not inhibited by cyanide. More glycerol and phosphorus are utilized in processes of vital activity. Therefore, a sharp change of pH values causes profound changes in the metabolism of the yeast cell."}
{"id": "PMID:13274", "title": "[Chitinase of Bacillus thuringiensis].", "content": "Strains of Bacillus thuringiensis were shown to hydrolyse various forms of chitin around growing colonies on a solid medium. In conditions of submerged cultivation on a medium containing demineralized crab shells, Bac. thuringiensis var. caucasicus INMI Arm. 837 manifests the chitinolytic activity at the beginning of the stationary growth phase. The activity of chitinase which is of a constitutive nature increases when the bacterium is cultivated at pH 7.2. The maximum rate of hydrolysis of colloid chitin by chitinase prepared from the cultural broth is displayed at pH 8.0 and 60 degrees C.", "contents": "[Chitinase of Bacillus thuringiensis]. Strains of Bacillus thuringiensis were shown to hydrolyse various forms of chitin around growing colonies on a solid medium. In conditions of submerged cultivation on a medium containing demineralized crab shells, Bac. thuringiensis var. caucasicus INMI Arm. 837 manifests the chitinolytic activity at the beginning of the stationary growth phase. The activity of chitinase which is of a constitutive nature increases when the bacterium is cultivated at pH 7.2. The maximum rate of hydrolysis of colloid chitin by chitinase prepared from the cultural broth is displayed at pH 8.0 and 60 degrees C."}
{"id": "PMID:13291", "title": "Two membrane sites for DNA synthesis in Pneumococcus.", "content": "A DNA membrane fraction extracted from pneumococci can be separated into two subfractions with respect to macromolecular composition and DNA synthesis by centrifugation in a 30-60% w/v neutral sucrose gradient. Each fraction can be rebanded in a sucrose gradient or centrifuged to equilibrium in a CsCl density gradient without altering the ability of the fractions to synthesize DNA. The fast sedimenting (heavy) fraction contains 45% of the DNA, and the bulk of the phospholipid, protein, and RNA. The light fraction contains 50% of the DNA, and lower, but significant amounts of phospholipid, RNA, and protein. Both fractions contain a DNA replication complex consisting of a number of enzymes involved in synthesizing DNA or DNA precursors, as well as RNA polymerase activity. However, the specific activity of DNA polymerase in the light fraction is much greater than that in the heavy fraction. In addition, the following results suggest that the former is concerned primarily with replication of the genome while the latter has characteristics of a repair function for the genome. (1) newly synthesized DNA can be detected within 30 s in the light fraction but not until 4 min in the heavy fraction. (2) an RNA-DNA single-stranded hybrid can be demonstrated during initial stages of DNA synthesis in the light, but not heavy fraction. (3) extensive semiconservative DNA replication occurs in the light fraction, whereas little such replication is detected in the heavy fraction. (4) DNA polymerase activity in the light fraction has several of the characteristics of a polymerase identified by others as being concerned with normal DNA replication, such as inhibition by N-ethylmaleimide, and relatively high rates of chain elongation (4.9 x 10(4) nucleotides/min). In contrast, DNA polymerase activity in the heavy fraction has characteristic properties associated with DNA polymerase I, a possible repair enzyme. These include higher activity for a d(A-T)n template than that detected in the light fraction, no effect of N-ethylmaleimide, and relatively low rates of chain elongation (9 x 10(3) nucleotides/min).", "contents": "Two membrane sites for DNA synthesis in Pneumococcus. A DNA membrane fraction extracted from pneumococci can be separated into two subfractions with respect to macromolecular composition and DNA synthesis by centrifugation in a 30-60% w/v neutral sucrose gradient. Each fraction can be rebanded in a sucrose gradient or centrifuged to equilibrium in a CsCl density gradient without altering the ability of the fractions to synthesize DNA. The fast sedimenting (heavy) fraction contains 45% of the DNA, and the bulk of the phospholipid, protein, and RNA. The light fraction contains 50% of the DNA, and lower, but significant amounts of phospholipid, RNA, and protein. Both fractions contain a DNA replication complex consisting of a number of enzymes involved in synthesizing DNA or DNA precursors, as well as RNA polymerase activity. However, the specific activity of DNA polymerase in the light fraction is much greater than that in the heavy fraction. In addition, the following results suggest that the former is concerned primarily with replication of the genome while the latter has characteristics of a repair function for the genome. (1) newly synthesized DNA can be detected within 30 s in the light fraction but not until 4 min in the heavy fraction. (2) an RNA-DNA single-stranded hybrid can be demonstrated during initial stages of DNA synthesis in the light, but not heavy fraction. (3) extensive semiconservative DNA replication occurs in the light fraction, whereas little such replication is detected in the heavy fraction. (4) DNA polymerase activity in the light fraction has several of the characteristics of a polymerase identified by others as being concerned with normal DNA replication, such as inhibition by N-ethylmaleimide, and relatively high rates of chain elongation (4.9 x 10(4) nucleotides/min). In contrast, DNA polymerase activity in the heavy fraction has characteristic properties associated with DNA polymerase I, a possible repair enzyme. These include higher activity for a d(A-T)n template than that detected in the light fraction, no effect of N-ethylmaleimide, and relatively low rates of chain elongation (9 x 10(3) nucleotides/min)."}
{"id": "PMID:13292", "title": "Biochemical, genetic, and regulatory studies of alanine catabolism in Escherichia coli K12.", "content": "E. coli K12 was found to utilise both D-and L-stereoisomers of alanine as sole sources of carbon, nitrogen and energy for growth. This capability was absolutely dependent upon the possession of an active membrane-bound D-alanine dehydrogenase, and was lost by mutants in which the enzyme was defective. The Michaelis constant for the enzyme with D-alanine as substrate was 30 mM, and the pH optimum about 8.9. D-alanine was the most active substrate, L-alanine was inactive and several other D-amino acids were 10--50% as active as D-alanine. Oxidation of D-alanine was linked to oxygen via a cytochrome-containing respiratory chain. Synthesis of the dehydrogenase was induced 16 to 23-fold by incubation with D- or L-alanine, but only D-alanine was intrinsically active as an inducer. L-alanine was active either as a substrate or inducer only in t he presence of an uninhibited alanine racemase which converted it to the D-isomer. The map-location of their structural genes between ara and leu, together with other similarities, indicate that D-alanine dehydrogenase and the \"alaninase\" of Wijsman (1972a) are the same enzyme. Both D- and L-alanine were intrinsically active as inducers of alanine racemase synthesis. The synthesis of both D-alanine dehydrogenase and alanine racemase was found to be regulated by catabolite repression.", "contents": "Biochemical, genetic, and regulatory studies of alanine catabolism in Escherichia coli K12. E. coli K12 was found to utilise both D-and L-stereoisomers of alanine as sole sources of carbon, nitrogen and energy for growth. This capability was absolutely dependent upon the possession of an active membrane-bound D-alanine dehydrogenase, and was lost by mutants in which the enzyme was defective. The Michaelis constant for the enzyme with D-alanine as substrate was 30 mM, and the pH optimum about 8.9. D-alanine was the most active substrate, L-alanine was inactive and several other D-amino acids were 10--50% as active as D-alanine. Oxidation of D-alanine was linked to oxygen via a cytochrome-containing respiratory chain. Synthesis of the dehydrogenase was induced 16 to 23-fold by incubation with D- or L-alanine, but only D-alanine was intrinsically active as an inducer. L-alanine was active either as a substrate or inducer only in t he presence of an uninhibited alanine racemase which converted it to the D-isomer. The map-location of their structural genes between ara and leu, together with other similarities, indicate that D-alanine dehydrogenase and the \"alaninase\" of Wijsman (1972a) are the same enzyme. Both D- and L-alanine were intrinsically active as inducers of alanine racemase synthesis. The synthesis of both D-alanine dehydrogenase and alanine racemase was found to be regulated by catabolite repression."}
{"id": "PMID:13298", "title": "[Treatment of ischemic heart disease with \"coronary drugs\" (author's transl)].", "content": "The standard treatment of ischemic heart disease consists in the administration of nitrates and beta-sympathicolytic agents. Calcium antagonists are likewise promising. They should be used particularly if beta-sympathicolytic agents are contraindicated. In the beginning special caution should be exercised on combining a beta-sympathicolytic agent with a calcium antagonist. This is best done under clinical supervision since sudden cardiac decompensation, extreme bradycardia and/or disturbed atrioventricular conduction is to be expected. Today the administration of \"coronary dilators\" is no longer a part of the standard treatment but can at best be regarded as supplementary therapy.", "contents": "[Treatment of ischemic heart disease with \"coronary drugs\" (author's transl)]. The standard treatment of ischemic heart disease consists in the administration of nitrates and beta-sympathicolytic agents. Calcium antagonists are likewise promising. They should be used particularly if beta-sympathicolytic agents are contraindicated. In the beginning special caution should be exercised on combining a beta-sympathicolytic agent with a calcium antagonist. This is best done under clinical supervision since sudden cardiac decompensation, extreme bradycardia and/or disturbed atrioventricular conduction is to be expected. Today the administration of \"coronary dilators\" is no longer a part of the standard treatment but can at best be regarded as supplementary therapy."}
{"id": "PMID:13304", "title": "Lytic enzymes in the autolysis of filamentous fungi.", "content": "The degrees of autolysis attained by five different genera of filamentous fungi during an incubation period of 60 days, under the same culture conditions were: 87.3% for Penicillium oxalicum; 65.9% for Neurospora crassa; 62.7% for Polystictus versicolor; 51.7% for Aspergillus niger and 23.5% for Nectria galligena. N. crassa, A. niger and P. versicolor reached the end of the autolysis during this incubation period (60 days), whereas P. oxalicum and N. galligena did not. The excretion of the lytic enzymes beta-N-acetylglucosaminidase, beta -1-3 glucanase, chitinase, invertase and acid phosphatase into the culture medium during growth and autolysis was investigated. The excretion of these enzymes was consistent with the degree of autolysis reached, the maximum excretion belonging to P. oxalicum and the minimum to N. galligena. The N. crassa invertase was excreted into the culture liquid at levels very much higher than the other enzymes studied, and at levels very much higher than the invertases excreted by the other fungi.", "contents": "Lytic enzymes in the autolysis of filamentous fungi. The degrees of autolysis attained by five different genera of filamentous fungi during an incubation period of 60 days, under the same culture conditions were: 87.3% for Penicillium oxalicum; 65.9% for Neurospora crassa; 62.7% for Polystictus versicolor; 51.7% for Aspergillus niger and 23.5% for Nectria galligena. N. crassa, A. niger and P. versicolor reached the end of the autolysis during this incubation period (60 days), whereas P. oxalicum and N. galligena did not. The excretion of the lytic enzymes beta-N-acetylglucosaminidase, beta -1-3 glucanase, chitinase, invertase and acid phosphatase into the culture medium during growth and autolysis was investigated. The excretion of these enzymes was consistent with the degree of autolysis reached, the maximum excretion belonging to P. oxalicum and the minimum to N. galligena. The N. crassa invertase was excreted into the culture liquid at levels very much higher than the other enzymes studied, and at levels very much higher than the invertases excreted by the other fungi."}
{"id": "PMID:13305", "title": "Methylation and aging in Rhizoctonia solani.", "content": "Our earlier studies had shown that as fungi age, many of their vital functions decrease; in Rhizoctonia solani, protein synthesis is one of the functions so affected. We now find that the ability to methylate tRNA, a vital component of the protein synthesizing system, also decreases with age. This methylation of Escherichia coli tRNA by R. solani methylase preparations increased with the concentration of enzyme and with time of incubation; in both cases the rate of increase was considerably higher for preparations from young cells than for those from old cells. The methylation reaction also increased with the concentration of substrate tRNA, with temperature, at least to 45 degrees C, and with pH to 9.0. Methylase preparations from R. solani methylated both exogenous E. coli tRNA and yeast tRNA, but were only weakly active on isolated R. solani tRNA. However, acid-precipitated methylases from R. solani were very effective in methylating the homologous exogenous tRNA. Regardless of the source of the tRNA used as substrate, the methylases from older cells were always less active than those from young cells from the same mycelium. No methylase inhibitor was detected in the fungus.", "contents": "Methylation and aging in Rhizoctonia solani. Our earlier studies had shown that as fungi age, many of their vital functions decrease; in Rhizoctonia solani, protein synthesis is one of the functions so affected. We now find that the ability to methylate tRNA, a vital component of the protein synthesizing system, also decreases with age. This methylation of Escherichia coli tRNA by R. solani methylase preparations increased with the concentration of enzyme and with time of incubation; in both cases the rate of increase was considerably higher for preparations from young cells than for those from old cells. The methylation reaction also increased with the concentration of substrate tRNA, with temperature, at least to 45 degrees C, and with pH to 9.0. Methylase preparations from R. solani methylated both exogenous E. coli tRNA and yeast tRNA, but were only weakly active on isolated R. solani tRNA. However, acid-precipitated methylases from R. solani were very effective in methylating the homologous exogenous tRNA. Regardless of the source of the tRNA used as substrate, the methylases from older cells were always less active than those from young cells from the same mycelium. No methylase inhibitor was detected in the fungus."}
{"id": "PMID:13306", "title": "Development of Chronomers for narcotic antagonists.", "content": "The object of this program is to prepare a bioerodable naltrexone delivery system which can be implanted subcataneously in human and which can relieve the narcotic antagonist over 1-6 months at relatively constant and sufficient rates to block the euphoric effect of morphine based drugs. The system is composed of naltrexone uniformly dispersed in a solid hydropholic CHRONOMER matrix which undergoes predictable surface erosion when exposed to an aqueous medium. Kinetic studies in vitro have been carried out during the course of the program to determine the best composition for the system. Toxilogical studies conducted at ALZA during the past 2 years have not revealed limiting adverse effects of either the CHRONOMER materials or their hydrolysis products. The tail-flick test procedure was used to measure the effectiveness of naltrexone to antagonize the analgesis of morphine in rats. Naltrexone infused intravenously at doses of 4 and 16 ug/kg/hr resulted in, after 6 hours, 54 and 89 per cent antagonism, respectively, against a 63.5 per cent effective dose of morphine. Preliminary sterilization studies showed that no adverse effects to CHRONOMER/naltrexone systems occurred after exposure to 2.5 or 5.0 mrads of 60Co irradiation.", "contents": "Development of Chronomers for narcotic antagonists. The object of this program is to prepare a bioerodable naltrexone delivery system which can be implanted subcataneously in human and which can relieve the narcotic antagonist over 1-6 months at relatively constant and sufficient rates to block the euphoric effect of morphine based drugs. The system is composed of naltrexone uniformly dispersed in a solid hydropholic CHRONOMER matrix which undergoes predictable surface erosion when exposed to an aqueous medium. Kinetic studies in vitro have been carried out during the course of the program to determine the best composition for the system. Toxilogical studies conducted at ALZA during the past 2 years have not revealed limiting adverse effects of either the CHRONOMER materials or their hydrolysis products. The tail-flick test procedure was used to measure the effectiveness of naltrexone to antagonize the analgesis of morphine in rats. Naltrexone infused intravenously at doses of 4 and 16 ug/kg/hr resulted in, after 6 hours, 54 and 89 per cent antagonism, respectively, against a 63.5 per cent effective dose of morphine. Preliminary sterilization studies showed that no adverse effects to CHRONOMER/naltrexone systems occurred after exposure to 2.5 or 5.0 mrads of 60Co irradiation."}
{"id": "PMID:13310", "title": "Octopamine.", "content": "Octopamine is highly concentrated in neurones of several invertebrate species. Unlike in mammals, octopaminergic neurones in invertebrates are spatially separated from catecholaminergic neurons. In identified nerve cells of Aplysia, however, this amine coexists with other putative neurotransmitters. Octopamine is synthesized in nerves from tyrosine and tyramine and metabolised mainly by monoamine oxidase. When lobster nerves are depolarized, octopamine is liberated by a Ca2+-dependent process. A specific adenylate cyclase is stimulated by octopamine in several invertebrates to activate phosphorylase in the cockroach, induce a light-flash in firefly lattern or inhibit rhythm contractions in locust muscle. All of these observations provide compelling evidence that octopamine is a neurotransmitter in invertebrates. In mammals octopamine is localised in nerves in peripheral tissues and brain where it seems to coexist with noradrenaline, the catecholamine being present in much higher concentrations. Octopamine is released from nerves together with noradrenaline and it may under certain conditions modify the actions of the adrenergic neurotransmitter. Octopamine is present in unusually high concentrations in certain neurological and hepatic diseases and may have a pathophysiological role.", "contents": "Octopamine. Octopamine is highly concentrated in neurones of several invertebrate species. Unlike in mammals, octopaminergic neurones in invertebrates are spatially separated from catecholaminergic neurons. In identified nerve cells of Aplysia, however, this amine coexists with other putative neurotransmitters. Octopamine is synthesized in nerves from tyrosine and tyramine and metabolised mainly by monoamine oxidase. When lobster nerves are depolarized, octopamine is liberated by a Ca2+-dependent process. A specific adenylate cyclase is stimulated by octopamine in several invertebrates to activate phosphorylase in the cockroach, induce a light-flash in firefly lattern or inhibit rhythm contractions in locust muscle. All of these observations provide compelling evidence that octopamine is a neurotransmitter in invertebrates. In mammals octopamine is localised in nerves in peripheral tissues and brain where it seems to coexist with noradrenaline, the catecholamine being present in much higher concentrations. Octopamine is released from nerves together with noradrenaline and it may under certain conditions modify the actions of the adrenergic neurotransmitter. Octopamine is present in unusually high concentrations in certain neurological and hepatic diseases and may have a pathophysiological role."}
{"id": "PMID:13311", "title": "Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus.", "content": "The effects of diazepam, flunitrazepam, phenobarbitone and baclofen on excitatory as well as on pre- and postsynaptic inhibitory processes in the cuneate nucleus were studied in decerebrate cats. Afferent presynaptic inhibition in the cuneate nucleus, evoked by volleys in the median nerve, and assessed by the size of the positive cuneate surface potential (P wave), the dorsal column reflex (DCR), and the increased excitability of primary afferent terminals of the ulnar nerve, was markedly enhanced by diazepam (0.1-3.0 mg/kh i.v.) and flunitrazepam (0.01-0.3 mg/kg i.v.), slightly enhanced by lower doses of phenobarbitone (3-20 mg/kg i.v.), but depressed by baclofen (1-10 mg/kg i.v.). Diazepam, flunitrazepam and phenobarbitone also increased postsynaptic inhibition in the cuneate nucleus which was measured by the decrease after conditioning volleys in the median nerve of the short-latency lemniscal response to cuneate stimulation. The GABA receptor blocking agent, picrotoxin, antagonized the effects of diazepam on pre- and postsynaptic inhibition in a surmountable way. After thiosemicarbazide (TSC), an inhibitor of GABA synthesis, both pre- and postsynaptic inhibition were greatly reduced and the augmenting effect of diazepam on both types of inhibition was nearly abolished. Aminooxyacetic acid (AOAA), an inhibitor of GABA degradation, slightly enhanced pre- and postsynaptic inhibition; the effects of diazepam were unaffected by AOAA. Diazepam, flunitrazepam and phenobarbitone did not alter the resting excitability of primary afferent endings or of cuneo-thalamic relay (CTR) cells in the cuneate nucleus. After higher doses (30 mg/kg i.v.) of phenobarbitone pre- and postsynaptic inhibition, which were enhanced by 10 mg/kg of this drug, tended to return to pre-drug values or below. Phenobarbitone, in contrast to benzodiazepines, also depressed in a dose-dependent way the N wave, which is an index of the orthodromic excitation of the CTR cells. Baclofen strongly depressed the cuneate N wave, decreased the excitability of CTR cells, reduced pre- and postsynaptic inhibition, but had no effect on the resting excitability of primary afferent endings. Our findings suggest the following modes of action of the above mentioned drugs: 1. benzodiazepines enhance selectively the GABA-mediated pre- and postsynaptic inhibition in the cuneate nucleus; 2. phenobarbitone slightly enhances pre- and postsynaptic inhibition only in a narrow dose range, and in addition reduces the excitatory processes in the cuneate nucleus; 3. baclofen seems to depress the excitation of cuneate relay cells and interneurones postsynaptically; the depression of relay cells is probably nonspecific.", "contents": "Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus. The effects of diazepam, flunitrazepam, phenobarbitone and baclofen on excitatory as well as on pre- and postsynaptic inhibitory processes in the cuneate nucleus were studied in decerebrate cats. Afferent presynaptic inhibition in the cuneate nucleus, evoked by volleys in the median nerve, and assessed by the size of the positive cuneate surface potential (P wave), the dorsal column reflex (DCR), and the increased excitability of primary afferent terminals of the ulnar nerve, was markedly enhanced by diazepam (0.1-3.0 mg/kh i.v.) and flunitrazepam (0.01-0.3 mg/kg i.v.), slightly enhanced by lower doses of phenobarbitone (3-20 mg/kg i.v.), but depressed by baclofen (1-10 mg/kg i.v.). Diazepam, flunitrazepam and phenobarbitone also increased postsynaptic inhibition in the cuneate nucleus which was measured by the decrease after conditioning volleys in the median nerve of the short-latency lemniscal response to cuneate stimulation. The GABA receptor blocking agent, picrotoxin, antagonized the effects of diazepam on pre- and postsynaptic inhibition in a surmountable way. After thiosemicarbazide (TSC), an inhibitor of GABA synthesis, both pre- and postsynaptic inhibition were greatly reduced and the augmenting effect of diazepam on both types of inhibition was nearly abolished. Aminooxyacetic acid (AOAA), an inhibitor of GABA degradation, slightly enhanced pre- and postsynaptic inhibition; the effects of diazepam were unaffected by AOAA. Diazepam, flunitrazepam and phenobarbitone did not alter the resting excitability of primary afferent endings or of cuneo-thalamic relay (CTR) cells in the cuneate nucleus. After higher doses (30 mg/kg i.v.) of phenobarbitone pre- and postsynaptic inhibition, which were enhanced by 10 mg/kg of this drug, tended to return to pre-drug values or below. Phenobarbitone, in contrast to benzodiazepines, also depressed in a dose-dependent way the N wave, which is an index of the orthodromic excitation of the CTR cells. Baclofen strongly depressed the cuneate N wave, decreased the excitability of CTR cells, reduced pre- and postsynaptic inhibition, but had no effect on the resting excitability of primary afferent endings. Our findings suggest the following modes of action of the above mentioned drugs: 1. benzodiazepines enhance selectively the GABA-mediated pre- and postsynaptic inhibition in the cuneate nucleus; 2. phenobarbitone slightly enhances pre- and postsynaptic inhibition only in a narrow dose range, and in addition reduces the excitatory processes in the cuneate nucleus; 3. baclofen seems to depress the excitation of cuneate relay cells and interneurones postsynaptically; the depression of relay cells is probably nonspecific."}
{"id": "PMID:13312", "title": "The effect of tris(2-chloroethyl)amine on human hemoglobin.", "content": "The reaction of tris(2-chloroethyl)amine (TCEA) with purified hemoglobin and its effect on properties of hemoglobin was studied using 14C-labeled TCEA. Hemoglobin remained soluble after binding as much as 4 TCEA per heme. In concentrations which did not denature hemoglobin TCEA reacted only with a small proportion of the free SH groups; blockade of the SH groups with PMB did not noticeably affect the binding of TCEA to hemoglobin. Hydrolysis by trypsin or chymotrypsin of hemoglobin which had reacted with TCEA yielded radioactive peptides besides not radioactive peptides and radioactive compounds not reacting with ninhydrin. The reaction with TCEA caused a change in electrophoretic mobility of hemoglobin and prevented its complete disintegration by PMB into subunits. After reaction with TCEA the affinity of hemoglobin for oxygen was strongly increased and the heme-heme interaction strongly diminished. The Bohr effect and the effect of 2,3-diphosphoglycerate on oxygen affinity remained unchanged. The effect of TCEA on the properties of hemoglobin points to specificity in its reaction with functional groups of hemoglobin.", "contents": "The effect of tris(2-chloroethyl)amine on human hemoglobin. The reaction of tris(2-chloroethyl)amine (TCEA) with purified hemoglobin and its effect on properties of hemoglobin was studied using 14C-labeled TCEA. Hemoglobin remained soluble after binding as much as 4 TCEA per heme. In concentrations which did not denature hemoglobin TCEA reacted only with a small proportion of the free SH groups; blockade of the SH groups with PMB did not noticeably affect the binding of TCEA to hemoglobin. Hydrolysis by trypsin or chymotrypsin of hemoglobin which had reacted with TCEA yielded radioactive peptides besides not radioactive peptides and radioactive compounds not reacting with ninhydrin. The reaction with TCEA caused a change in electrophoretic mobility of hemoglobin and prevented its complete disintegration by PMB into subunits. After reaction with TCEA the affinity of hemoglobin for oxygen was strongly increased and the heme-heme interaction strongly diminished. The Bohr effect and the effect of 2,3-diphosphoglycerate on oxygen affinity remained unchanged. The effect of TCEA on the properties of hemoglobin points to specificity in its reaction with functional groups of hemoglobin."}
{"id": "PMID:13313", "title": "Effects of cimetidine on adenylate cyclase activity of guinea pig gastric mucosa stimulated by histamine, sodium fluoride and 5'-guanylylimidodiphosphate.", "content": "Cimetidine, a recently developed histamine H2-receptor blocking agent has been shown to be a potent inhibitor of histamine-stimulated gastric acid secretion in rat, cat, dog and man. To study the mode of action of cimetidine the modification of stimulatory effects of histamine, sodium flouride and 5'-guanylylimidodiphosphate by cimetidine on the adenylate cyclase activity of guinea pig gastric mucosa was studied. The effect of cimetidine was also compared to that of metiamide, an older histamine H2-receptor antagonist. The effect of cimetidine was qualitatively similar to that of metiamide, i.e. a selective blockade of histamine H2-receptors. Quantitatively cimetidine was about 10-fold more potent than metiamide.", "contents": "Effects of cimetidine on adenylate cyclase activity of guinea pig gastric mucosa stimulated by histamine, sodium fluoride and 5'-guanylylimidodiphosphate. Cimetidine, a recently developed histamine H2-receptor blocking agent has been shown to be a potent inhibitor of histamine-stimulated gastric acid secretion in rat, cat, dog and man. To study the mode of action of cimetidine the modification of stimulatory effects of histamine, sodium flouride and 5'-guanylylimidodiphosphate by cimetidine on the adenylate cyclase activity of guinea pig gastric mucosa was studied. The effect of cimetidine was also compared to that of metiamide, an older histamine H2-receptor antagonist. The effect of cimetidine was qualitatively similar to that of metiamide, i.e. a selective blockade of histamine H2-receptors. Quantitatively cimetidine was about 10-fold more potent than metiamide."}
{"id": "PMID:13314", "title": "Beta-adrenergic receptors in guinea-pig myocardial tissue.", "content": "Stereospecific binding sites for (-) [3H]-alprenolol, a beta-adrenergic antagonist, have been identified in guinea-pig myocardial broken cell preparations. The concentration of the sites was 0.3 pmoles per mg of protein and the dissociation constant (at 37 degrees C) 10(-8) M. A close correlation between the ability of various beta-adrenergic antagonists to compete with tracer alprenolol binding and to block the response of isoprenaline-stimulated myocardial adenylate cyclase has been found. Low affinity sites for the labelled beta-adrenergic antagonist in contrast to stereospecific sites are heat stable and do not discriminate between the (-) and the (+) forms of the beta-adrenergic antagonists. Adenylate cyclase in guinea-pig myocardial tissue is poorly stimulated by isoprenaline or 5'-guanylylimidodiphosphate. This is attributed to a high basal activity which could be lowered by a preincubation at 37 degrees C.", "contents": "Beta-adrenergic receptors in guinea-pig myocardial tissue. Stereospecific binding sites for (-) [3H]-alprenolol, a beta-adrenergic antagonist, have been identified in guinea-pig myocardial broken cell preparations. The concentration of the sites was 0.3 pmoles per mg of protein and the dissociation constant (at 37 degrees C) 10(-8) M. A close correlation between the ability of various beta-adrenergic antagonists to compete with tracer alprenolol binding and to block the response of isoprenaline-stimulated myocardial adenylate cyclase has been found. Low affinity sites for the labelled beta-adrenergic antagonist in contrast to stereospecific sites are heat stable and do not discriminate between the (-) and the (+) forms of the beta-adrenergic antagonists. Adenylate cyclase in guinea-pig myocardial tissue is poorly stimulated by isoprenaline or 5'-guanylylimidodiphosphate. This is attributed to a high basal activity which could be lowered by a preincubation at 37 degrees C."}
{"id": "PMID:13315", "title": "Dopaminergic neurons: an in vivo system for measuring drug interactions with presynaptic receptors.", "content": "An in vivo system has been used to investigate the ability of dopamine agonists and antagonists to alter dopamine synthesis by acting at what appear to be presynaptic dopamine receptors. In order to eliminate postsynaptically induced changes in dopamine synthesis caused by the effects of these drugs on the firing rate of dopamine neurons, gammabutyrolactone was administered to block impulse flow in the nigro-neostriatal pathway. The accumulation of Dopa in the rat striatum after administration of Dopa decarboxylase inhibitor was used as an index of striatal tyrosine hydroxylase activity. It was found that administration of the dopamine agonists, apomorphine or ET-495 [1-(2-pyrimidyl)-piperonyl-piperazine], modified the apparent activity of striatal tyrosine hydroxylase when impulse flow was blocked in dopamine neurons. This presynaptic effect of apomorphine could be prevented by low doses of loxapine haloperidol and spiroperidol. Chlorpromazine, fluphenazine, and thioridizine were much less effective than the butyrophenones in blocking the effects of apomorphine. Molindone and (+) butaclamol, but not (-) butaclamol, reversed the presynaptic agonist effects, pimozide was a weak blocker and clozapine had no effect at all. All these neuroleptics except (-) butaclamol caused a significant increase in Dopa accumulation when impulse flow was intact. Compared with haloperidol the phenothiazines and pimozide appeared less potent in reversing the presynaptic effects of apomorphine than in blocking the behavioral effects of this agonist. Possible functional significance of the presynaptic dopamine receptors are considered.", "contents": "Dopaminergic neurons: an in vivo system for measuring drug interactions with presynaptic receptors. An in vivo system has been used to investigate the ability of dopamine agonists and antagonists to alter dopamine synthesis by acting at what appear to be presynaptic dopamine receptors. In order to eliminate postsynaptically induced changes in dopamine synthesis caused by the effects of these drugs on the firing rate of dopamine neurons, gammabutyrolactone was administered to block impulse flow in the nigro-neostriatal pathway. The accumulation of Dopa in the rat striatum after administration of Dopa decarboxylase inhibitor was used as an index of striatal tyrosine hydroxylase activity. It was found that administration of the dopamine agonists, apomorphine or ET-495 [1-(2-pyrimidyl)-piperonyl-piperazine], modified the apparent activity of striatal tyrosine hydroxylase when impulse flow was blocked in dopamine neurons. This presynaptic effect of apomorphine could be prevented by low doses of loxapine haloperidol and spiroperidol. Chlorpromazine, fluphenazine, and thioridizine were much less effective than the butyrophenones in blocking the effects of apomorphine. Molindone and (+) butaclamol, but not (-) butaclamol, reversed the presynaptic agonist effects, pimozide was a weak blocker and clozapine had no effect at all. All these neuroleptics except (-) butaclamol caused a significant increase in Dopa accumulation when impulse flow was intact. Compared with haloperidol the phenothiazines and pimozide appeared less potent in reversing the presynaptic effects of apomorphine than in blocking the behavioral effects of this agonist. Possible functional significance of the presynaptic dopamine receptors are considered."}
{"id": "PMID:13316", "title": "Electromechanical studies of an Anemonia sulcata toxin in mammalian cardiac muscle.", "content": "1. In guinea-pig papillary muscles toxin II isolated from the sea anemone Anemonia sulcata (ATX) enhanced the force of contraction without changing the time-to-peak tension. ATX increased the relaxation time. The positive inotropic effect was accompanied by a prolongation in action potential duration. The action potential amplitude and the resting membrane potential remained essentially unchanged. The velocity of depolarization (dV/dtmax) decreased slightly. The effects werenot modified by pretreatment of the animals with reserpine. 2. In preparations partially depolarized by elevated extracellular potassium (14.7 mM KCl) a concentration of 1 X 10(-8) M ATX was ineffective with respect to increase in force of contraction or delay of repolarization. The effects of 1 X 10(-8) M ATX could be reversed by 5 X 10(-7) M tetrodotoxin. 3. Our results suggest that ATX affects the action potential duration by delaying the inactivation of the fast sodium permeability change which initiates the action potential. It is not clear, however, in which manner this effect is related to the increase in force of contraction.", "contents": "Electromechanical studies of an Anemonia sulcata toxin in mammalian cardiac muscle. 1. In guinea-pig papillary muscles toxin II isolated from the sea anemone Anemonia sulcata (ATX) enhanced the force of contraction without changing the time-to-peak tension. ATX increased the relaxation time. The positive inotropic effect was accompanied by a prolongation in action potential duration. The action potential amplitude and the resting membrane potential remained essentially unchanged. The velocity of depolarization (dV/dtmax) decreased slightly. The effects werenot modified by pretreatment of the animals with reserpine. 2. In preparations partially depolarized by elevated extracellular potassium (14.7 mM KCl) a concentration of 1 X 10(-8) M ATX was ineffective with respect to increase in force of contraction or delay of repolarization. The effects of 1 X 10(-8) M ATX could be reversed by 5 X 10(-7) M tetrodotoxin. 3. Our results suggest that ATX affects the action potential duration by delaying the inactivation of the fast sodium permeability change which initiates the action potential. It is not clear, however, in which manner this effect is related to the increase in force of contraction."}
{"id": "PMID:13317", "title": "Analysis of the actions of cimetidine and metiamide on gastric acid secretion in the isolated guinea pig gastric mucosa.", "content": "Cumulative dose-response curves for histamine were determined on acid secretion from the isolated guinea pig gastric mucosa. Two H2-receptor antagonists-metiamide and cimetidine-behaved like competitive antagonists to histamine on gastric acid secretion in vitro. The isolated guinea pig gastric mucosa seems to be a suitable in vitro model for analysing the action of compounds on receptors involved in acid secretion.", "contents": "Analysis of the actions of cimetidine and metiamide on gastric acid secretion in the isolated guinea pig gastric mucosa. Cumulative dose-response curves for histamine were determined on acid secretion from the isolated guinea pig gastric mucosa. Two H2-receptor antagonists-metiamide and cimetidine-behaved like competitive antagonists to histamine on gastric acid secretion in vitro. The isolated guinea pig gastric mucosa seems to be a suitable in vitro model for analysing the action of compounds on receptors involved in acid secretion."}
{"id": "PMID:13321", "title": "[Effect of pH on properties of the cholinoreceptive membrane of snail neurons].", "content": "The influence of pH on acetylcholine (ACh)-induced responses in completely isolated neurons of Lymnaea stagnalis was studied under voltage clapm conditions. The pH drop lead to a decrease in sensitivity of cholinoreceptive membrane; at pH 5.8-6.0 ACh-responses were eliminated completely. When raising the external pH (up to 10.6) there were no changes in the ACh effect. A group responsible for sensitivity changes of the cholinoreceptive membrane appears to have pK about 6.7. It is shown that the pH drop does not influence the ionic channel functional groups. The results can be explained in the assumption that some functionally important groups in the cholinoreceptor active site are protonated at low pH.", "contents": "[Effect of pH on properties of the cholinoreceptive membrane of snail neurons]. The influence of pH on acetylcholine (ACh)-induced responses in completely isolated neurons of Lymnaea stagnalis was studied under voltage clapm conditions. The pH drop lead to a decrease in sensitivity of cholinoreceptive membrane; at pH 5.8-6.0 ACh-responses were eliminated completely. When raising the external pH (up to 10.6) there were no changes in the ACh effect. A group responsible for sensitivity changes of the cholinoreceptive membrane appears to have pK about 6.7. It is shown that the pH drop does not influence the ionic channel functional groups. The results can be explained in the assumption that some functionally important groups in the cholinoreceptor active site are protonated at low pH."}
{"id": "PMID:13322", "title": "Immune system to uremia.", "content": "Pneumonia [4,9] and septicemia are still the principle causes of the high mortality in acute renal failure. Moreover, according to the EDTA report, 19% of chronic intermittent dialysis patients die from infection [17]. The resulting conclusion, that cellular and humoral immune responses are suppressed in renal insufficiency, is further supported by experimental evidence.", "contents": "Immune system to uremia. Pneumonia [4,9] and septicemia are still the principle causes of the high mortality in acute renal failure. Moreover, according to the EDTA report, 19% of chronic intermittent dialysis patients die from infection [17]. The resulting conclusion, that cellular and humoral immune responses are suppressed in renal insufficiency, is further supported by experimental evidence."}
{"id": "PMID:13323", "title": "In vitro release of ACTH from dispersed rat pars intermedia cells. II. Effect of neurotransmitter substances.", "content": "Studies were carried out to test the responsiveness of dispersed pars intermedia (PI) cells to a number of neurotransmitter substances known to be present in the PI. These substances were tested over an extended dose range. The catecholamines, adrenaline, noradrenaline, and dopamine inactivated PI ACTH at high concentrations; at lower concentrations, they were without effect. Histamine and carbachol had no effect on ACTH release. 5-hydroxytryptamine stimulated ACTH release in a dose-related manner, from 10(-6) to 10(-3)M, while having no effect on ACTH release from the pars distalis (PD). We conclude that the release of ACTH from the PI may be controlled by direct serotonergic innervation.", "contents": "In vitro release of ACTH from dispersed rat pars intermedia cells. II. Effect of neurotransmitter substances. Studies were carried out to test the responsiveness of dispersed pars intermedia (PI) cells to a number of neurotransmitter substances known to be present in the PI. These substances were tested over an extended dose range. The catecholamines, adrenaline, noradrenaline, and dopamine inactivated PI ACTH at high concentrations; at lower concentrations, they were without effect. Histamine and carbachol had no effect on ACTH release. 5-hydroxytryptamine stimulated ACTH release in a dose-related manner, from 10(-6) to 10(-3)M, while having no effect on ACTH release from the pars distalis (PD). We conclude that the release of ACTH from the PI may be controlled by direct serotonergic innervation."}
{"id": "PMID:13326", "title": "Mental disturbed violent offenders in Sweden.", "content": "Among perpetrators of crimes of violence against persons submitted to psychiatric examination, 16 men with severe mental disorder have been examined by standardized psychologic tests and clinical interviews. Objective anamnestic data have been used to assess social background, individual development and onset of mental disorder. Psychotic as well as nonpsychotic men reacted with violence against threat to the offender's physical existence of his self image. In most instances ego weakness or depleted mental energy exaggerated the feeling of threat or stymied the ability to choose alternative solutions. Abuse of alcohol and narcotics and acute inebriation often weakened self-control and triggered of the act of violence.", "contents": "Mental disturbed violent offenders in Sweden. Among perpetrators of crimes of violence against persons submitted to psychiatric examination, 16 men with severe mental disorder have been examined by standardized psychologic tests and clinical interviews. Objective anamnestic data have been used to assess social background, individual development and onset of mental disorder. Psychotic as well as nonpsychotic men reacted with violence against threat to the offender's physical existence of his self image. In most instances ego weakness or depleted mental energy exaggerated the feeling of threat or stymied the ability to choose alternative solutions. Abuse of alcohol and narcotics and acute inebriation often weakened self-control and triggered of the act of violence."}
{"id": "PMID:13327", "title": "Cerebrospinal fluid changes in experimental cardiopulmonary bypass using hemodilution with glucose water.", "content": "Cardiopulmonary bypass using hemodilution with isotonic glucose water was performed on seven dogs. Intense systemic metabolic acidosis, hyponatremia, hypochloremia, and hyperglycemia were accompanied by only comparatively small changes in the corresponding cerebrospinal fluid values. The data suggested that in the present study, cardiopulmonary bypass was not associated with gross disruptions of the barriers for bicarbonate, sodium, chloride, and glucose between blood and cerebrospinal fluid.", "contents": "Cerebrospinal fluid changes in experimental cardiopulmonary bypass using hemodilution with glucose water. Cardiopulmonary bypass using hemodilution with isotonic glucose water was performed on seven dogs. Intense systemic metabolic acidosis, hyponatremia, hypochloremia, and hyperglycemia were accompanied by only comparatively small changes in the corresponding cerebrospinal fluid values. The data suggested that in the present study, cardiopulmonary bypass was not associated with gross disruptions of the barriers for bicarbonate, sodium, chloride, and glucose between blood and cerebrospinal fluid."}
{"id": "PMID:13333", "title": "The association of umbilical cord complications and variable decelerations with acid-base findings.", "content": "Variable decelerations during the last 2 hours of labor were associated with an abnormally positioned umbilical cord at delivery in 52% of cases. In cases where an abnormally positioned umbilical cord was seen at delivery, 89% had been preceded by variable decelerations. Cord compression resulted in an A-V difference in pH that was significantly increased when compared to a control group. This was mainly due to a decrease in the pH of the umbilical artery. The pathophysiology of cord compression is discussed.", "contents": "The association of umbilical cord complications and variable decelerations with acid-base findings. Variable decelerations during the last 2 hours of labor were associated with an abnormally positioned umbilical cord at delivery in 52% of cases. In cases where an abnormally positioned umbilical cord was seen at delivery, 89% had been preceded by variable decelerations. Cord compression resulted in an A-V difference in pH that was significantly increased when compared to a control group. This was mainly due to a decrease in the pH of the umbilical artery. The pathophysiology of cord compression is discussed."}
{"id": "PMID:13336", "title": "Dental management of patients undergoing bone marrow transplantation for aplastic anemia.", "content": "Acquired aplastic anemia is a rare hematologic disease characterized by a hypoplastic bone marrow and peripheral pnacytopenia. In severe cases, where conservative medical management has been unsuccessful, bone marrow transplantation is now being performed. Between the years 1971 and 1975, twenty-two patients with severe aplastic anemia were seen at the Children's Hospital Medical Center. This article discusses the oral presentations of aplastic anemia and the dental management of nine patients without and thirteen with transplantations.", "contents": "Dental management of patients undergoing bone marrow transplantation for aplastic anemia. Acquired aplastic anemia is a rare hematologic disease characterized by a hypoplastic bone marrow and peripheral pnacytopenia. In severe cases, where conservative medical management has been unsuccessful, bone marrow transplantation is now being performed. Between the years 1971 and 1975, twenty-two patients with severe aplastic anemia were seen at the Children's Hospital Medical Center. This article discusses the oral presentations of aplastic anemia and the dental management of nine patients without and thirteen with transplantations."}
{"id": "PMID:13337", "title": "Hormone production in ovarian carcinomas. Histochemical approach in stroma reaction.", "content": "Enzymatically active stromal cells (EASC) in different ovarian tumors are concerned with hormon production. 198 cases of ovarian tumors were investigated by different histochemical methods. Distribution of lactate-and glucose-6-phosphate-dehydrogenase was investigated by plaimetric measurement.--EASC were found in benign ovarian tumors in 48%, in malignant in 30%. They are found exclusively in ovarian tumors and are completely absent in metastases. Incidence is dependent on histological type of tumor. With regard to untreated ovarian carcinoma containing EASC, these cells cover an aerea of 1.9% (0.5-5.9%). EASC occur in a very high percentage after menopause and are reduced by chemotherapy or radioation. Incidence of EASC in ovarian tumors is in relation with postmenopausal bleeding. Glandular-cystic endometrium is noticed only in connection with EASC. There is a positive relation between the quantity of EASC and the incidence of bleeding.--EASC are characterized by a strong NADP-dependent-dehydrogenase-reaction and reactions for lactate-, malate-dehydrogenases and alcaline phosphatases. Apart from that these cells are not all uniform. It seems that the enzymatically active fibrocytes are the first step of theca-like cells which are then luteinized and finally filled up with cholesterol. Histochemistry of EASC in comparison with other steroid-producing tissues make possible, that these cells have an estrogenic and more seldomly also an androgenic activity.", "contents": "Hormone production in ovarian carcinomas. Histochemical approach in stroma reaction. Enzymatically active stromal cells (EASC) in different ovarian tumors are concerned with hormon production. 198 cases of ovarian tumors were investigated by different histochemical methods. Distribution of lactate-and glucose-6-phosphate-dehydrogenase was investigated by plaimetric measurement.--EASC were found in benign ovarian tumors in 48%, in malignant in 30%. They are found exclusively in ovarian tumors and are completely absent in metastases. Incidence is dependent on histological type of tumor. With regard to untreated ovarian carcinoma containing EASC, these cells cover an aerea of 1.9% (0.5-5.9%). EASC occur in a very high percentage after menopause and are reduced by chemotherapy or radioation. Incidence of EASC in ovarian tumors is in relation with postmenopausal bleeding. Glandular-cystic endometrium is noticed only in connection with EASC. There is a positive relation between the quantity of EASC and the incidence of bleeding.--EASC are characterized by a strong NADP-dependent-dehydrogenase-reaction and reactions for lactate-, malate-dehydrogenases and alcaline phosphatases. Apart from that these cells are not all uniform. It seems that the enzymatically active fibrocytes are the first step of theca-like cells which are then luteinized and finally filled up with cholesterol. Histochemistry of EASC in comparison with other steroid-producing tissues make possible, that these cells have an estrogenic and more seldomly also an androgenic activity."}
{"id": "PMID:13339", "title": "Preponderance of beta adrenergic receptors in the gastric fundus of the rat.", "content": "There are two kinds of adrenergic receptors in rat fundus (stomach), the alpha receptors are stimulated with adrenaline and noradrenaline and can be blocked effectively with azapetine and the beta receptors are stimulated with isoprenaline and adrenaline and can be blocked effectively with propranolol. Adrenaline, noradrenaline and isoprenaline all produce inhibition of acetylcholine induced contractions in both untreated and reserpinized tissues that can be antagonized with azapetine and propranolol on its specific receptors but propranolol has a greater capacity to decrease the sensitivity of both untreated and reserpinized tissues to isoprenaline and adrenaline than azapetine can in case of noradrenaline and adrenaline.", "contents": "Preponderance of beta adrenergic receptors in the gastric fundus of the rat. There are two kinds of adrenergic receptors in rat fundus (stomach), the alpha receptors are stimulated with adrenaline and noradrenaline and can be blocked effectively with azapetine and the beta receptors are stimulated with isoprenaline and adrenaline and can be blocked effectively with propranolol. Adrenaline, noradrenaline and isoprenaline all produce inhibition of acetylcholine induced contractions in both untreated and reserpinized tissues that can be antagonized with azapetine and propranolol on its specific receptors but propranolol has a greater capacity to decrease the sensitivity of both untreated and reserpinized tissues to isoprenaline and adrenaline than azapetine can in case of noradrenaline and adrenaline."}
{"id": "PMID:13340", "title": "Methods in coccidiosis research: separation of oocysts from faeces.", "content": "Factors which may be important in the large-scale extraction of coccidial oocysts from faeces ha.ve been investigated with Eimeria tenella. Age of bird, inoculum, feeding status at the time of inoculation, period of collection, feeding status during collection, collection medium, homogenization and sieving, flotation, washing, sporulation and further purification have all been considered. The aim has been to establish a method to produce the maximum number of oocysts of a required degree of purity and viability, with the expenditure of the minimum amount of physical effort, time, animals and chemicals. In our method, groups of chickens 3-4 weeks of age are inoculated with 5000 oocysts of E. tenella and food is supplied ad lib. Over the period 5-8 days after inoculation, faeces are collected in trays containing 2% (w/v) potassium dichromate solution, while food intake is restricted. The faecal material is homogenized, passed once through 40 and 100 mesh sieves, centrifuged and the oocysts recovered from the sediment by 3 flotations in saturated salt solution. Following washing, oocysts are sporulated by forced aeration at 30 degrees C and may be further purified by hypochlorite treatment, or passage in 5% Tween 80 solution through a glass bead column followed by sucrose density gradient centrifugation. Routine passages along these lines over a 5 year period have given a recovery of 46% of the oocysts excreted by over 7000 birds.", "contents": "Methods in coccidiosis research: separation of oocysts from faeces. Factors which may be important in the large-scale extraction of coccidial oocysts from faeces ha.ve been investigated with Eimeria tenella. Age of bird, inoculum, feeding status at the time of inoculation, period of collection, feeding status during collection, collection medium, homogenization and sieving, flotation, washing, sporulation and further purification have all been considered. The aim has been to establish a method to produce the maximum number of oocysts of a required degree of purity and viability, with the expenditure of the minimum amount of physical effort, time, animals and chemicals. In our method, groups of chickens 3-4 weeks of age are inoculated with 5000 oocysts of E. tenella and food is supplied ad lib. Over the period 5-8 days after inoculation, faeces are collected in trays containing 2% (w/v) potassium dichromate solution, while food intake is restricted. The faecal material is homogenized, passed once through 40 and 100 mesh sieves, centrifuged and the oocysts recovered from the sediment by 3 flotations in saturated salt solution. Following washing, oocysts are sporulated by forced aeration at 30 degrees C and may be further purified by hypochlorite treatment, or passage in 5% Tween 80 solution through a glass bead column followed by sucrose density gradient centrifugation. Routine passages along these lines over a 5 year period have given a recovery of 46% of the oocysts excreted by over 7000 birds."}
{"id": "PMID:13341", "title": "[Synovial fluid. Review of international literature from 1972 to 1975 (author's transl)].", "content": "The tremendous increase in the number of articles from the world scientific literature dealing with the synovial fluid in recent years, reflects the growing interest of research on that subject. The current review summarizes the scientific works published during the period of 1972 to 1975. This review deals with fundamental as well as applied research or clinical reports adding some diagnostic hints in the knowledge of diseases involving joints. The content of the review is divided in two major chapters. 1) The Physico-Chemical Properties of the Synovial Fluid (viscosity, pH,...); 2) The Composition of the Synovial Fluid (proteins, carbohydrates, lipids, prostaglandins, cells, crystals, micro-organisms).", "contents": "[Synovial fluid. Review of international literature from 1972 to 1975 (author's transl)]. The tremendous increase in the number of articles from the world scientific literature dealing with the synovial fluid in recent years, reflects the growing interest of research on that subject. The current review summarizes the scientific works published during the period of 1972 to 1975. This review deals with fundamental as well as applied research or clinical reports adding some diagnostic hints in the knowledge of diseases involving joints. The content of the review is divided in two major chapters. 1) The Physico-Chemical Properties of the Synovial Fluid (viscosity, pH,...); 2) The Composition of the Synovial Fluid (proteins, carbohydrates, lipids, prostaglandins, cells, crystals, micro-organisms)."}
{"id": "PMID:13342", "title": "Three group treatments for reduction of speech anxiety among students.", "content": "Conditions of group systematic desensitization (n = 8), group flooding (n = 7), and a group discussion-placebo control treatment (n = 4) were employed to reduce anxiety about public-speaking in university students. Three 90-min. sessions were provided. Pre- and posttreatment assessments employed self-report and behavioral measures. The desensitization group showed significant pre- to posttreatment change across all self-report measures, whereas the flooding and control groups showed similar improvement on only one such measure. No group showed significant improvement on the behavioral measure. Groups did not exhibit significant intergroup differences in improvement on any measure.", "contents": "Three group treatments for reduction of speech anxiety among students. Conditions of group systematic desensitization (n = 8), group flooding (n = 7), and a group discussion-placebo control treatment (n = 4) were employed to reduce anxiety about public-speaking in university students. Three 90-min. sessions were provided. Pre- and posttreatment assessments employed self-report and behavioral measures. The desensitization group showed significant pre- to posttreatment change across all self-report measures, whereas the flooding and control groups showed similar improvement on only one such measure. No group showed significant improvement on the behavioral measure. Groups did not exhibit significant intergroup differences in improvement on any measure."}
{"id": "PMID:13343", "title": "Lactate content and pH in muscle obtained after dynamic exercise.", "content": "Analyzes were made on muscle samples taken from the lateral part of the m. quadriceps femoris of man (lactate, pyruvate, and pH) on venous blood (lactate, pyruvate) and on capillary blood (pH). Samples were taken at rest, immediately after termination of dynamic exercise and during 20 min recovery from exhaustive dynamic exercise. Muscle pH decreases from 7.08 atrest to 6.60 at exhaustion. Decrease in muscle pH was linearly related to muscle content of lactate + pyruvate. The relationship was slightly different from what has been obtained after isometric exercise and this difference was ascribed to acid-base exchange with the blood during dynamic exercise. Lactate content was highly elevated in muscle after exercise and the concentration was 2-3 times higher than in blood. Pyruvate content was, however, only slightly higher than that at rest. During recovery, lactate content of muscle decreased exponentially with respect to time, whereas pyruvate content increased. The half-time of lactate decrease was 9.5 min. From the lactate dehydrogenase equilibrium relative values on NADH/NAD ratio could be calculated. It was found that NADH/NAD was highly increased after exercise and that it had not returned to the basal value after 20 min recovery.", "contents": "Lactate content and pH in muscle obtained after dynamic exercise. Analyzes were made on muscle samples taken from the lateral part of the m. quadriceps femoris of man (lactate, pyruvate, and pH) on venous blood (lactate, pyruvate) and on capillary blood (pH). Samples were taken at rest, immediately after termination of dynamic exercise and during 20 min recovery from exhaustive dynamic exercise. Muscle pH decreases from 7.08 atrest to 6.60 at exhaustion. Decrease in muscle pH was linearly related to muscle content of lactate + pyruvate. The relationship was slightly different from what has been obtained after isometric exercise and this difference was ascribed to acid-base exchange with the blood during dynamic exercise. Lactate content was highly elevated in muscle after exercise and the concentration was 2-3 times higher than in blood. Pyruvate content was, however, only slightly higher than that at rest. During recovery, lactate content of muscle decreased exponentially with respect to time, whereas pyruvate content increased. The half-time of lactate decrease was 9.5 min. From the lactate dehydrogenase equilibrium relative values on NADH/NAD ratio could be calculated. It was found that NADH/NAD was highly increased after exercise and that it had not returned to the basal value after 20 min recovery."}
{"id": "PMID:13344", "title": "The interstitial pH of the working gastrocnemius muscle of the dog.", "content": "In isolated gastrocnemius muscles from 19 dogs the interstitial H+ activity ([H+]int) was measured with bulb-type buffer-filled glass minielectrodes. The muscles were working isotonically and perfused with blood. In addition arterial and venous pH, venous O2 saturation, muscle temperature, and blood flow were meausred continuously at rest, during 12 min of sustained exercise, and in the recovery period. Lactate (LA-) release and O2 consumption were calculated by the Fick principle. The experiments were performed under normal acid-base conditions and during artificially induced metabolic acidosis and alkalosis. 1. In normal acid-base balance [H+]int at rest was 54 +/- 3.3 neq/l (= pH 7.24), while venous H+ ([H+]ven) was 45 +/- 4.7 neq/l (= pH 7.34) A[H+] gradient was always observed between interstitial fluid and venous blood. 2. Immediately after onset of exercise [H+]int decreased transiently. After about 15 s [H+]int increased rapidly up to values of 105 +/- 7 neq/l (= pH 6.98). In the recovery period [H+]int diminished and reached control values after about 20-30 min. [H+]ven increased up to 74.4 +/- 8.4 neq/l (= pH 7.13). Maximal gradients between [H+]int and [H+]ven were 36 neq/l (= pH 0.2). 3. During repeated exercise the decrease in [H+]int at the onset of exercise was more extensive, while the subsequent increase was lowered. These changes correspond to a smaller LA- release. 4. During metabolic alkalosis at the onset of exercise [h+]int decreased less, during metabolic acidosis more than under normal acid-base conditions. Thereafter during metabolic alkalosis maximal values of 95.4 +/ 2 neq/l (= pH 7.03), during metabolic acidosis of 180 +/- 8.6 neq/l (= pH 6.74) were reached. This led to [H+] gradients between interstitial fluid and venous blood which were much higher in metabolic acidosis than in normal acid-base balance or in metabolic alkalosis. In metabolic acidosis [H+]int decreased very sle rapidly than during metabolic alkalosis or during normal acid-base conditions. It is concluded that the H+ activity measured is that within the interstitial space. Exercise hyperemia is not caused by changes of [H+]int. Mechanisms are discussed which may explain H+ gradients between interstitial fluid and venous blood and rapid changes of [H+]int at the onset of exercise.", "contents": "The interstitial pH of the working gastrocnemius muscle of the dog. In isolated gastrocnemius muscles from 19 dogs the interstitial H+ activity ([H+]int) was measured with bulb-type buffer-filled glass minielectrodes. The muscles were working isotonically and perfused with blood. In addition arterial and venous pH, venous O2 saturation, muscle temperature, and blood flow were meausred continuously at rest, during 12 min of sustained exercise, and in the recovery period. Lactate (LA-) release and O2 consumption were calculated by the Fick principle. The experiments were performed under normal acid-base conditions and during artificially induced metabolic acidosis and alkalosis. 1. In normal acid-base balance [H+]int at rest was 54 +/- 3.3 neq/l (= pH 7.24), while venous H+ ([H+]ven) was 45 +/- 4.7 neq/l (= pH 7.34) A[H+] gradient was always observed between interstitial fluid and venous blood. 2. Immediately after onset of exercise [H+]int decreased transiently. After about 15 s [H+]int increased rapidly up to values of 105 +/- 7 neq/l (= pH 6.98). In the recovery period [H+]int diminished and reached control values after about 20-30 min. [H+]ven increased up to 74.4 +/- 8.4 neq/l (= pH 7.13). Maximal gradients between [H+]int and [H+]ven were 36 neq/l (= pH 0.2). 3. During repeated exercise the decrease in [H+]int at the onset of exercise was more extensive, while the subsequent increase was lowered. These changes correspond to a smaller LA- release. 4. During metabolic alkalosis at the onset of exercise [h+]int decreased less, during metabolic acidosis more than under normal acid-base conditions. Thereafter during metabolic alkalosis maximal values of 95.4 +/ 2 neq/l (= pH 7.03), during metabolic acidosis of 180 +/- 8.6 neq/l (= pH 6.74) were reached. This led to [H+] gradients between interstitial fluid and venous blood which were much higher in metabolic acidosis than in normal acid-base balance or in metabolic alkalosis. In metabolic acidosis [H+]int decreased very sle rapidly than during metabolic alkalosis or during normal acid-base conditions. It is concluded that the H+ activity measured is that within the interstitial space. Exercise hyperemia is not caused by changes of [H+]int. Mechanisms are discussed which may explain H+ gradients between interstitial fluid and venous blood and rapid changes of [H+]int at the onset of exercise."}
{"id": "PMID:13346", "title": "Phosphate transfer and tubular pH during renal stopped flow microperfusion experiments in the rat.", "content": "The loss of 32P-phosphate salts by the luminal compartment of cortical tubules was studied in control and in acetazolamide-infused rats, during stopped-flow microperfusion with 100 mM phosphate-raffinose solutions. When the initial pH of the perfusion solution was low (5.5), phosphate was lost more rapidly from proximal tubules than at high initial pH (8.2). The average half-time of phosphate loss was 31.9 s during acid, and 66.0 s during alkaline perfusion in proximal tubules of control rats; in acetazolamide-infused rats half-times were 77.0 and 86.6 s for acid and alkaline perfusions. Thus acetazolamide infusion slows the rate of phosphate loss by proximal tubules, when the perfusion solution is acid, but has no significant effect if its pH is alkaline. These half-times compare to proximal acidification rates of 7.23 s in control and 13.2 s in acetazolamide-infused rats. In distal tubules of control rats no significant loss of phosphate was observed during the period of perfusion. It is concluded that the loss of phosphate, in proximal tubules, is markedly slower than the changes in tubular pH and so its effect on tubular acidification must be of minor importance. In distal tubules changes in pH are not due to transepithelial phosphate movement.", "contents": "Phosphate transfer and tubular pH during renal stopped flow microperfusion experiments in the rat. The loss of 32P-phosphate salts by the luminal compartment of cortical tubules was studied in control and in acetazolamide-infused rats, during stopped-flow microperfusion with 100 mM phosphate-raffinose solutions. When the initial pH of the perfusion solution was low (5.5), phosphate was lost more rapidly from proximal tubules than at high initial pH (8.2). The average half-time of phosphate loss was 31.9 s during acid, and 66.0 s during alkaline perfusion in proximal tubules of control rats; in acetazolamide-infused rats half-times were 77.0 and 86.6 s for acid and alkaline perfusions. Thus acetazolamide infusion slows the rate of phosphate loss by proximal tubules, when the perfusion solution is acid, but has no significant effect if its pH is alkaline. These half-times compare to proximal acidification rates of 7.23 s in control and 13.2 s in acetazolamide-infused rats. In distal tubules of control rats no significant loss of phosphate was observed during the period of perfusion. It is concluded that the loss of phosphate, in proximal tubules, is markedly slower than the changes in tubular pH and so its effect on tubular acidification must be of minor importance. In distal tubules changes in pH are not due to transepithelial phosphate movement."}
{"id": "PMID:13345", "title": "Studies on the lithium transport across the red cell membrane. II. Characterization of ouabain-sensitive and ouabain-insensitive Li+ transport. Effects of bicarbonate and dipyridamole.", "content": "In studies on Li+ net-transport across the human red cell membrane following results were obtained: 1. In K+- and Na+-free choline chloride media, Li+ is transported into the erythrocytes against an electrochemical gradient. This Li+ uphill transport as well as Li+ downhill transport into the cells is inhibited by ouabain, ATP-depletion, and by external K+ and Na+. The effects of K+ and Na+ are relieved at high Li+ concentrations. 2. Ouabain-sensitive Li+ uptake, determined at 10 mM external Na+, does not obey simple Michaelis-Menten kinetics and exhibits a maximum at about pH 7. 3. Ouabain-resistant Li+ downhill transport into erythrocytes increases with rising pH. It is comprised of a saturating component and a component linearly dependent on external Li+. The linear component is partly inhibited by dipyridamole and accelerated by bicarbonate. The bicarbonate effect can be completely blocked by dipyridamole, phlorizin and phenylbutazone. 4. Li+ release is not inhibited by ouabain, ATP-depletion and external K+. It increases with external Na+ concentration, tending to saturate at 150 mM Na+. Na+-independent Li+ release is stimulated by bicarbonate. It is concluded that ouabain-sensitive Li+ uptake is mediated at the K+-site(s) of the Na+-K+ pump. Li+, K+ and Na+ appear to compete for a common site (or sites). The stimulation of Li+ transfer by bicarbonate and the inhibition by dipyridamole suggest a participation of anionic species in ouabain-resistant Li+ transfer. The Na+-dependent Li+ release and the \"saturating component\" of Li+ uptake are ascribed to the Na+-dependent Li+ countertransport system.", "contents": "Studies on the lithium transport across the red cell membrane. II. Characterization of ouabain-sensitive and ouabain-insensitive Li+ transport. Effects of bicarbonate and dipyridamole. In studies on Li+ net-transport across the human red cell membrane following results were obtained: 1. In K+- and Na+-free choline chloride media, Li+ is transported into the erythrocytes against an electrochemical gradient. This Li+ uphill transport as well as Li+ downhill transport into the cells is inhibited by ouabain, ATP-depletion, and by external K+ and Na+. The effects of K+ and Na+ are relieved at high Li+ concentrations. 2. Ouabain-sensitive Li+ uptake, determined at 10 mM external Na+, does not obey simple Michaelis-Menten kinetics and exhibits a maximum at about pH 7. 3. Ouabain-resistant Li+ downhill transport into erythrocytes increases with rising pH. It is comprised of a saturating component and a component linearly dependent on external Li+. The linear component is partly inhibited by dipyridamole and accelerated by bicarbonate. The bicarbonate effect can be completely blocked by dipyridamole, phlorizin and phenylbutazone. 4. Li+ release is not inhibited by ouabain, ATP-depletion and external K+. It increases with external Na+ concentration, tending to saturate at 150 mM Na+. Na+-independent Li+ release is stimulated by bicarbonate. It is concluded that ouabain-sensitive Li+ uptake is mediated at the K+-site(s) of the Na+-K+ pump. Li+, K+ and Na+ appear to compete for a common site (or sites). The stimulation of Li+ transfer by bicarbonate and the inhibition by dipyridamole suggest a participation of anionic species in ouabain-resistant Li+ transfer. The Na+-dependent Li+ release and the \"saturating component\" of Li+ uptake are ascribed to the Na+-dependent Li+ countertransport system."}
{"id": "PMID:13347", "title": "The influence on breeding, production, and acid-base balance when mink are fed on acidified feed.", "content": "It has been shown, partly in an investigation in which female mink were subject to increasing quantities of acid in their feed, and partly in an investigation of experimental animals which were fed with various concentrations of acid-preserved fishsilage, that there is a marked risk for a change of the acid-base balance to a metabolic acidosis when pH in the feed comes lower than 5. These investigations are also considered to show that mink's reproductive ability and general welfare is considerably affected when fed with large quantities of acid-preserved fish feed over a longer period, possibly because of alterations in the acid base balance. It is possible to reduce or avoid metabolic acidosis in mink by neutralizing silage or feed.", "contents": "The influence on breeding, production, and acid-base balance when mink are fed on acidified feed. It has been shown, partly in an investigation in which female mink were subject to increasing quantities of acid in their feed, and partly in an investigation of experimental animals which were fed with various concentrations of acid-preserved fishsilage, that there is a marked risk for a change of the acid-base balance to a metabolic acidosis when pH in the feed comes lower than 5. These investigations are also considered to show that mink's reproductive ability and general welfare is considerably affected when fed with large quantities of acid-preserved fish feed over a longer period, possibly because of alterations in the acid base balance. It is possible to reduce or avoid metabolic acidosis in mink by neutralizing silage or feed."}
{"id": "PMID:13350", "title": "Surface activity of some psychotropic drugs.", "content": "Diazepam was found to be the most surface active substance in aqueous solutions, chlorpromazine was less active and the lowest activity was found for haloperidol. The surface activity in blood was similar. The effect of pH on the surface activity of chlorpromazine solutions was observed.", "contents": "Surface activity of some psychotropic drugs. Diazepam was found to be the most surface active substance in aqueous solutions, chlorpromazine was less active and the lowest activity was found for haloperidol. The surface activity in blood was similar. The effect of pH on the surface activity of chlorpromazine solutions was observed."}
{"id": "PMID:13351", "title": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part 1. Log k--pH profile for sulfadimidine solvolysis.", "content": "The degradation of sulfadimidine (SDMP) in the pH range 5-83--10-0, at 403, 411 and 418 K, was investigated by UV spectrophotometry. Semilogarythmic plots (A242--A') vs. time in 0-1 M HCl for the degradation of SDMP in the above pH range were linear. The log k--pH profile constructed from the experimental results served for estimation of specific rate constants and pKa values. These, in turn, were used to calculate the theoretical log k--pH profile, acc. to the equation for the rate of reaction proportional to the concentration of the dissociated form of SDMP, in the pH range 5-8--10. Thermodynamic parameters of the reaction--energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined.", "contents": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part 1. Log k--pH profile for sulfadimidine solvolysis. The degradation of sulfadimidine (SDMP) in the pH range 5-83--10-0, at 403, 411 and 418 K, was investigated by UV spectrophotometry. Semilogarythmic plots (A242--A') vs. time in 0-1 M HCl for the degradation of SDMP in the above pH range were linear. The log k--pH profile constructed from the experimental results served for estimation of specific rate constants and pKa values. These, in turn, were used to calculate the theoretical log k--pH profile, acc. to the equation for the rate of reaction proportional to the concentration of the dissociated form of SDMP, in the pH range 5-8--10. Thermodynamic parameters of the reaction--energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined."}
{"id": "PMID:13352", "title": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part 2. Log k--pH profile for sulfadimidine autoxidation.", "content": "The overall first order rate constants for the reaction of degradation of sulfadimidine (kobs. = kOX+kh) in the presence of the air oxygen were determined from the measurements of absorbance in 0-1 M HCl at 243 nm, using \"the feathering technique\". The apparent first order rate constants for autoxidation of sulfadimidine at 403, 411 and 418 K, in the pH range 2-0--9-2 were calculated from the equation kOX = kobs. -- kh, where kh are the rate constants for hydrolysis carried out under nitrogen. The rate of sulfadimidine autoxidation is a function of concentration of the undissociated form (kOX = kOX-fHA). The thermodynamic parameters of the reaction: Ha, deltaHNo., deltaSNo. and logA were determined for the specific rate constant of autoxdiation (kOX).", "contents": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part 2. Log k--pH profile for sulfadimidine autoxidation. The overall first order rate constants for the reaction of degradation of sulfadimidine (kobs. = kOX+kh) in the presence of the air oxygen were determined from the measurements of absorbance in 0-1 M HCl at 243 nm, using \"the feathering technique\". The apparent first order rate constants for autoxidation of sulfadimidine at 403, 411 and 418 K, in the pH range 2-0--9-2 were calculated from the equation kOX = kobs. -- kh, where kh are the rate constants for hydrolysis carried out under nitrogen. The rate of sulfadimidine autoxidation is a function of concentration of the undissociated form (kOX = kOX-fHA). The thermodynamic parameters of the reaction: Ha, deltaHNo., deltaSNo. and logA were determined for the specific rate constant of autoxdiation (kOX)."}
{"id": "PMID:13348", "title": "Drug-drug interactions among residents in homes for the elderly: a pilot study.", "content": "This pilot study investigated epidemiologically the potential for clinically significant drug-drug interactions, a subclass of adverse drug responses, in two homes for the elderly. The agent (drugs), host (residents), and environment (rural and urban nursing homes) in the illness known as drug-drug interaction were studied. Drug profiles on 188 subjects were compiled and screened by computer. Of these, 100 (80 in the rural home and 20 in the urban home) had the potential for clinically significant drug-drug interactions. Laboratory diagnostic procedures essential to confirm the unintentional interaction of two or more drugs were beyond the scope of the study; therefore, physicians independently reviewed the records of 66 residents who could be interviewed, agreeing that 27 residents were potential drug-drug interactors. These subjects had twice as many drug products and three times as many pro re nata products prescribed for them as did subjects without the potential for drug-drug interaction. The possible cause of interaction found most frequently was digitalis combined with thiazide or furosemide. The results of this pilot study suggest several implications for practice within the research setting.", "contents": "Drug-drug interactions among residents in homes for the elderly: a pilot study. This pilot study investigated epidemiologically the potential for clinically significant drug-drug interactions, a subclass of adverse drug responses, in two homes for the elderly. The agent (drugs), host (residents), and environment (rural and urban nursing homes) in the illness known as drug-drug interaction were studied. Drug profiles on 188 subjects were compiled and screened by computer. Of these, 100 (80 in the rural home and 20 in the urban home) had the potential for clinically significant drug-drug interactions. Laboratory diagnostic procedures essential to confirm the unintentional interaction of two or more drugs were beyond the scope of the study; therefore, physicians independently reviewed the records of 66 residents who could be interviewed, agreeing that 27 residents were potential drug-drug interactors. These subjects had twice as many drug products and three times as many pro re nata products prescribed for them as did subjects without the potential for drug-drug interaction. The possible cause of interaction found most frequently was digitalis combined with thiazide or furosemide. The results of this pilot study suggest several implications for practice within the research setting."}
{"id": "PMID:13354", "title": "Esophageal reflux. Diagnosis and therapy.", "content": "Diagnosis of esophageal reflux often can be made on the basis of the characteristic symptoms of heartburn and regurgitation. When the picture is not so typical, acid reflux testing and esophageal biopsy appear to be the best indicators of esophageal reflux. Medical management is directed toward preventing reflux, neutralizing refluxed gastric contents, and enhancing clearance of refluxed material. Antacids are a mainstay of therapy, along with restrictions on diet and certain types of activity. If conservative therapy fails to control symptoms and stricture is likely to develop, surgery may be indicated.", "contents": "Esophageal reflux. Diagnosis and therapy. Diagnosis of esophageal reflux often can be made on the basis of the characteristic symptoms of heartburn and regurgitation. When the picture is not so typical, acid reflux testing and esophageal biopsy appear to be the best indicators of esophageal reflux. Medical management is directed toward preventing reflux, neutralizing refluxed gastric contents, and enhancing clearance of refluxed material. Antacids are a mainstay of therapy, along with restrictions on diet and certain types of activity. If conservative therapy fails to control symptoms and stricture is likely to develop, surgery may be indicated."}
{"id": "PMID:13355", "title": "The effect of beta-adrenoreceptive antagonists on the morbidity and mortality in cardiovascular disease.", "content": "The effect is critically reviewed of chronic administration of beta-adrenoreceptor antagonists on morbidity and mortality in angina pectoris and myocardial infarction. There is inconclusive evidence that the abrupt cessation of therapy with these agents may increase morbidity and mortality in angina pectoris. The type of anginal patient in which this may occur is not yet defined and neither is the mechanism. There is no evidence that beta-antagonists prolong the life of anginal patients. In the acute phase of experimental myocardial infarction, these drugs reduce mortality but do not do so in man. There is increasing evidence that they prolong life if administered to patients surviving the acute phase of myocardial infarction. The need for further studies is discussed.", "contents": "The effect of beta-adrenoreceptive antagonists on the morbidity and mortality in cardiovascular disease. The effect is critically reviewed of chronic administration of beta-adrenoreceptor antagonists on morbidity and mortality in angina pectoris and myocardial infarction. There is inconclusive evidence that the abrupt cessation of therapy with these agents may increase morbidity and mortality in angina pectoris. The type of anginal patient in which this may occur is not yet defined and neither is the mechanism. There is no evidence that beta-antagonists prolong the life of anginal patients. In the acute phase of experimental myocardial infarction, these drugs reduce mortality but do not do so in man. There is increasing evidence that they prolong life if administered to patients surviving the acute phase of myocardial infarction. The need for further studies is discussed."}
{"id": "PMID:13356", "title": "Recommending coronary artery surgery: refining judgement through application of new knowledge.", "content": "An analysis is made to help decide on the best form of treatment for atherosclerotic coronary disease. Available data on surgical treatment are reviewed with emphasis on prognosis and management of the patient with stable angina.", "contents": "Recommending coronary artery surgery: refining judgement through application of new knowledge. An analysis is made to help decide on the best form of treatment for atherosclerotic coronary disease. Available data on surgical treatment are reviewed with emphasis on prognosis and management of the patient with stable angina."}
{"id": "PMID:13353", "title": "Correlations between hydrophobicity and non-specific pharmacological effects of beta-adrenoceptor blocking agents.", "content": "It was the aim of this study to test whether the non-specific pharmacological activities of the beta-adrenergic blocking drugs can be predicted by estimation of the hydrophobicity of the compounds. Srong correlations were obtained between the octanol buffer partition coefficients and the ability of the drugs to decrease conduction velocity of the isolated frog heart, to raise the electrically induced ventricular fibrillation threshold in guinea pigs, and to depress ventricular contractility in the cat. The strong correlations between the partition coefficients and the pharmacological actions suggest that estimation of the hydrophobicity of the beta-adrenergic blocking drugs is suitable to predict the non-specific pharmacological properties.", "contents": "Correlations between hydrophobicity and non-specific pharmacological effects of beta-adrenoceptor blocking agents. It was the aim of this study to test whether the non-specific pharmacological activities of the beta-adrenergic blocking drugs can be predicted by estimation of the hydrophobicity of the compounds. Srong correlations were obtained between the octanol buffer partition coefficients and the ability of the drugs to decrease conduction velocity of the isolated frog heart, to raise the electrically induced ventricular fibrillation threshold in guinea pigs, and to depress ventricular contractility in the cat. The strong correlations between the partition coefficients and the pharmacological actions suggest that estimation of the hydrophobicity of the beta-adrenergic blocking drugs is suitable to predict the non-specific pharmacological properties."}
{"id": "PMID:13363", "title": "Rhodopsin in model membranes: charge displacements in interfacial layers.", "content": "A model membrane was developed in which interfacial layers of rhodopsin were reoriented onto one side of a thin Teflon film separating two aqueous compartments. Flashes evoked fast photoelectric signals (1 ms) that originated from capacitative charge displacements of oriented rhodopsin upon bleaching. The photoelectric responses of rhodopsin in the model membrane are compared with the early receptor potential of photoreceptor cells; it is concluded that the signals in both systems originate from the same mechanism.", "contents": "Rhodopsin in model membranes: charge displacements in interfacial layers. A model membrane was developed in which interfacial layers of rhodopsin were reoriented onto one side of a thin Teflon film separating two aqueous compartments. Flashes evoked fast photoelectric signals (1 ms) that originated from capacitative charge displacements of oriented rhodopsin upon bleaching. The photoelectric responses of rhodopsin in the model membrane are compared with the early receptor potential of photoreceptor cells; it is concluded that the signals in both systems originate from the same mechanism."}
{"id": "PMID:13359", "title": "[Polyarteritis nodosa with renal agenesis and immunosuppressive treatment].", "content": "A case of a 44 years old man with the unique combination of polyarteritis nodosa (PAN) and the congenital absence of a kidney is presented. The clinical picture consisted of fever, general symptoms, hypertermia, peripheric neuropathy, subcutaneous nodules and renal damage. Laboratory findings included increased WBC, telescoped urinary sediment, renal insufficiency, positive rheumatoid factor, policlonal gammopathy and positive Australia antigen. A review of the pertinent literature and the etiopathogenic role of Australia antigen in PAN is discussed. Efficacy of immunosuppressive therapy was evident in this case.", "contents": "[Polyarteritis nodosa with renal agenesis and immunosuppressive treatment]. A case of a 44 years old man with the unique combination of polyarteritis nodosa (PAN) and the congenital absence of a kidney is presented. The clinical picture consisted of fever, general symptoms, hypertermia, peripheric neuropathy, subcutaneous nodules and renal damage. Laboratory findings included increased WBC, telescoped urinary sediment, renal insufficiency, positive rheumatoid factor, policlonal gammopathy and positive Australia antigen. A review of the pertinent literature and the etiopathogenic role of Australia antigen in PAN is discussed. Efficacy of immunosuppressive therapy was evident in this case."}
{"id": "PMID:13364", "title": "Intramolecular general base-catalyzed ester hydrolyses by the imidazolyl group.", "content": "Intramolecular general base catalysis by the imidazolyl group was found in the hydrolyses of endo-5-[4;(5')-imidazolyl]-bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate in which the imidazolyl and trans-cinnamoyl groups are bound in close proximity to each other by rigid bicyclic rings. The rate constants for the intramolecular general base-catalyzed hydrolyses at 60 degrees are 6.4 X 10(-7) sec-1 for the former and 1.8 X 10(-7) sec-1 for the latter and the deuterium oxide solvent isotope effects are 3.0 for both. On the other hand, no intramolecular catalytic participation of the imidazolyl group was observed in the hydrolyses of the endo-exo isomers, exo- 5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5[4'(5')-imidazolyl]bicyclo[2.2.2]oct-exo-2-yl trans-cinnamate, in which the imidazolyl groups are located far from the trans-cinnamoyl groups. Intramolecular general base-catalyzed hydrolyses by the imidazolyl groups in endo-5[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate can serve as models of serine esterase-catalyzed hydrolyses.", "contents": "Intramolecular general base-catalyzed ester hydrolyses by the imidazolyl group. Intramolecular general base catalysis by the imidazolyl group was found in the hydrolyses of endo-5-[4;(5')-imidazolyl]-bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate in which the imidazolyl and trans-cinnamoyl groups are bound in close proximity to each other by rigid bicyclic rings. The rate constants for the intramolecular general base-catalyzed hydrolyses at 60 degrees are 6.4 X 10(-7) sec-1 for the former and 1.8 X 10(-7) sec-1 for the latter and the deuterium oxide solvent isotope effects are 3.0 for both. On the other hand, no intramolecular catalytic participation of the imidazolyl group was observed in the hydrolyses of the endo-exo isomers, exo- 5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5[4'(5')-imidazolyl]bicyclo[2.2.2]oct-exo-2-yl trans-cinnamate, in which the imidazolyl groups are located far from the trans-cinnamoyl groups. Intramolecular general base-catalyzed hydrolyses by the imidazolyl groups in endo-5[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate can serve as models of serine esterase-catalyzed hydrolyses."}
{"id": "PMID:13365", "title": "3':5'-cyclic AMP: independent induction of amino acid transport by epinephrine in primary cultures of adult rat liver cells.", "content": "Liver cells were obtained from adult rats by a collagenase perfusion technique and cultured as monolayers in serum-free media. Epinephrine and isoproterenol both induced large increases in intracellular adenosine 3':5'-monophosphate (cAMP) within 1-2 min whereas epinephrine (but not isoproterenol) induced 2- to 3-fold increases in the rate of alpha-aminoisobutyric acid transport within 2-4 hr after a 1 hr lag. Propranolol abolished the increase in cAMP elicited by epinephrine and isoproterenol, but did not block the induction of alpha-aminoisobutyric acid transport by epinephrine. In contrast, dihydroergotamine abolished and phentolamine diminished the induction of alpha-aminoisobutyric acid transport by epinephrine but did not decrease the stimulation of cAMP levels by epinephrine. Epinephrine dose response curves for cAMP and alpha-aminoisobutyric acid transport were similar. Once exposed to epinephrine, cells became refractory to further stimulation of cAMP levels by epinephrine.", "contents": "3':5'-cyclic AMP: independent induction of amino acid transport by epinephrine in primary cultures of adult rat liver cells. Liver cells were obtained from adult rats by a collagenase perfusion technique and cultured as monolayers in serum-free media. Epinephrine and isoproterenol both induced large increases in intracellular adenosine 3':5'-monophosphate (cAMP) within 1-2 min whereas epinephrine (but not isoproterenol) induced 2- to 3-fold increases in the rate of alpha-aminoisobutyric acid transport within 2-4 hr after a 1 hr lag. Propranolol abolished the increase in cAMP elicited by epinephrine and isoproterenol, but did not block the induction of alpha-aminoisobutyric acid transport by epinephrine. In contrast, dihydroergotamine abolished and phentolamine diminished the induction of alpha-aminoisobutyric acid transport by epinephrine but did not decrease the stimulation of cAMP levels by epinephrine. Epinephrine dose response curves for cAMP and alpha-aminoisobutyric acid transport were similar. Once exposed to epinephrine, cells became refractory to further stimulation of cAMP levels by epinephrine."}
{"id": "PMID:13366", "title": "Antigen-specific nonimmunoglobulin factor that neutralizes xenotropic virus is associated with mouse serum lipoproteins.", "content": "A soluble nonimmunoglobulin factor that specifically neutralizes mouse xenotropic C-type virus is found in normal mouse sera. It is stable from pH 2 to neutrality and resists ether extraction, freezing, or brief heating to 100 degrees. It can be separated from immunoglobulins by ultracentrifugation at a density of 1.21 g/cm3. Neutralizing activity is only found with the serum lipoproteins in the fraction with density less than 1.21 g/cm3.", "contents": "Antigen-specific nonimmunoglobulin factor that neutralizes xenotropic virus is associated with mouse serum lipoproteins. A soluble nonimmunoglobulin factor that specifically neutralizes mouse xenotropic C-type virus is found in normal mouse sera. It is stable from pH 2 to neutrality and resists ether extraction, freezing, or brief heating to 100 degrees. It can be separated from immunoglobulins by ultracentrifugation at a density of 1.21 g/cm3. Neutralizing activity is only found with the serum lipoproteins in the fraction with density less than 1.21 g/cm3."}
{"id": "PMID:13367", "title": "Inhibitors of genetic recombination in pneumococci.", "content": "Treatment of transformable pneumococci with DNA-intercalating agents shortly after the uptake of DNA molecules inhibited the appearance of genetic transformants. The same drug treatments applied 20 min after DNA uptake were ineffective. Ethidium bromide, proflavin, daunomycin, actinomycin D, and platinum red were found to be effective inhibitors. Donor DNA molecules reisolated from the drug-treated bacteria appeared to be associated with the resident DNA in an abnormal manner, and they had only poor transforming activity.", "contents": "Inhibitors of genetic recombination in pneumococci. Treatment of transformable pneumococci with DNA-intercalating agents shortly after the uptake of DNA molecules inhibited the appearance of genetic transformants. The same drug treatments applied 20 min after DNA uptake were ineffective. Ethidium bromide, proflavin, daunomycin, actinomycin D, and platinum red were found to be effective inhibitors. Donor DNA molecules reisolated from the drug-treated bacteria appeared to be associated with the resident DNA in an abnormal manner, and they had only poor transforming activity."}
{"id": "PMID:13368", "title": "Carcass components at first estrus of rats on high-fat and low-fat diets: body water, protein, and fat.", "content": "Carcass analysis data show that weanling rats fed high-fat (HF) and low-fat (LF) diets until the day of first estrus had similar body compositions at estrus, although the HF rats had estrus significantly earlier and at a lighter body weight (P less than 0.01) than the LF-diet rats. Total water as percent of wet weight, protein as percent of wet weight, and the water/protein ratios of the HF- and LF-diet rats did not differ significantly, whereas the absolute amounts of body water and protein of the two diet groups differed significantly (P less than 0.01), in accord with means (+/- SEM) of total body water as percent of wet weight were 66.2 +/- 0.3% for the HF rats and 66.4 +/- 0.3% for the LF-diet rats, whereas the mean absolute total body water for the two diet groups was 69.7 +/- 2.2 g and 81.1 +/- 2.4 g, respectively (P less than 0.01). Carcass fat of the HF rats, 15.6 +/- 1.0 g, was identical with that of the LF-diet rats, 15.6 +/- 0.9 g. The HF rats were therefore relatively fatter, 14.6 +/- 0.6 wet weight %, than the LF-diet rats, 12.6 +/- 0.4 wet weight % (0.05 greater than P greater than 0.01). The percentage of water in the fat-free wet weight of the HF rats, 77.5 +/- 0.3%, was significantly (P less than 0.01) greater than that of the LF-diet rats, 76.1 +/- 0.3%. These data and the high percentages of total water of body weight show that at first estrus the HF- and LF-diet rats had not as yet attained an adult body composition, similar to the human female at menarche. Within each diet group, the percentages of total water/body weight, protein/wet weight and fat/wet weight, or fat/dry weight, did not change significantly with increasing age of estrus, whereas each absolute carcass component--body water, protein, and fat--increased significantly with increasing age of estrus. The carcass data support G.C. Kennedy's hypothesis that a metabolic signal, related to fat stores, is a signal for puberty in the rat and are in accord with the hypothesis that a critical body composition of fatness is necessary for estrus in the rat, as in the human female. The greater relative fatness of the HF-diet rats may be associated with higher levels of estrogen in the HF rats than in the LF-diet rats.", "contents": "Carcass components at first estrus of rats on high-fat and low-fat diets: body water, protein, and fat. Carcass analysis data show that weanling rats fed high-fat (HF) and low-fat (LF) diets until the day of first estrus had similar body compositions at estrus, although the HF rats had estrus significantly earlier and at a lighter body weight (P less than 0.01) than the LF-diet rats. Total water as percent of wet weight, protein as percent of wet weight, and the water/protein ratios of the HF- and LF-diet rats did not differ significantly, whereas the absolute amounts of body water and protein of the two diet groups differed significantly (P less than 0.01), in accord with means (+/- SEM) of total body water as percent of wet weight were 66.2 +/- 0.3% for the HF rats and 66.4 +/- 0.3% for the LF-diet rats, whereas the mean absolute total body water for the two diet groups was 69.7 +/- 2.2 g and 81.1 +/- 2.4 g, respectively (P less than 0.01). Carcass fat of the HF rats, 15.6 +/- 1.0 g, was identical with that of the LF-diet rats, 15.6 +/- 0.9 g. The HF rats were therefore relatively fatter, 14.6 +/- 0.6 wet weight %, than the LF-diet rats, 12.6 +/- 0.4 wet weight % (0.05 greater than P greater than 0.01). The percentage of water in the fat-free wet weight of the HF rats, 77.5 +/- 0.3%, was significantly (P less than 0.01) greater than that of the LF-diet rats, 76.1 +/- 0.3%. These data and the high percentages of total water of body weight show that at first estrus the HF- and LF-diet rats had not as yet attained an adult body composition, similar to the human female at menarche. Within each diet group, the percentages of total water/body weight, protein/wet weight and fat/wet weight, or fat/dry weight, did not change significantly with increasing age of estrus, whereas each absolute carcass component--body water, protein, and fat--increased significantly with increasing age of estrus. The carcass data support G.C. Kennedy's hypothesis that a metabolic signal, related to fat stores, is a signal for puberty in the rat and are in accord with the hypothesis that a critical body composition of fatness is necessary for estrus in the rat, as in the human female. The greater relative fatness of the HF-diet rats may be associated with higher levels of estrogen in the HF rats than in the LF-diet rats."}
{"id": "PMID:13369", "title": "Extension of longevity in Drosophila mojavensis by environmental ethanol: differences between subraces.", "content": "Drosophila mojavensis adults, which breed and feed on necrotic cacti, show an increase in longevity when exposed to atmospheric ethanol. The increase in longevity is accompanied by retention of mature ovarioles and is independent of diet. Differences in longevity among strains from different localities were detected for females. Strains from Arizona and Sonora, Mexico, showed the greatest increase in longevity, while strains from Baja California, Mexico, showed the least increase. These differences may be controlled by the alcohol dehydrogenase locus, the octanol dehydrogenase locus, and modifier genes, because the aduld response is correlated with the frequency of alcohol dehydrogenase alleles, as well as second chromosomal inversions containing the octanol dehydrogenase locus. The longevity response is also consistent with the more uneven distribution and availability of the host plant in Arizona and Sonora, Mexico. Strains from Arizona and Sonora, Mexico, have a high frequency of Adh-S, the allele whose product is heat and pH tolerant. The host plant, organpipe cactus, exhibits extremes in temperature and pH in the same geographic region. Strains from Baja California, Mexico, possess a high frequency of Adh-F, whose product is heat and pH sensitive. The substrate in this region, agria cactus, has moderate temperature and pH extremes and contains relatively high concentrations of isopropanol. Isopropanol is presumable a selective agen favorable to Adh-F. The environmental heterogeneity that is proposed for maintaining the alleles at the alcohol dehydrogenase locus is the interaction of substrate alcohol content with temperature and pH. Substrates that do not contain appreciable amounts of isopropanol and are exposed to high temperatures and exhibit variable pH favor Adh-S, while substrates containing isopropanol and having moderate temperatures and pH favor Adh-F.", "contents": "Extension of longevity in Drosophila mojavensis by environmental ethanol: differences between subraces. Drosophila mojavensis adults, which breed and feed on necrotic cacti, show an increase in longevity when exposed to atmospheric ethanol. The increase in longevity is accompanied by retention of mature ovarioles and is independent of diet. Differences in longevity among strains from different localities were detected for females. Strains from Arizona and Sonora, Mexico, showed the greatest increase in longevity, while strains from Baja California, Mexico, showed the least increase. These differences may be controlled by the alcohol dehydrogenase locus, the octanol dehydrogenase locus, and modifier genes, because the aduld response is correlated with the frequency of alcohol dehydrogenase alleles, as well as second chromosomal inversions containing the octanol dehydrogenase locus. The longevity response is also consistent with the more uneven distribution and availability of the host plant in Arizona and Sonora, Mexico. Strains from Arizona and Sonora, Mexico, have a high frequency of Adh-S, the allele whose product is heat and pH tolerant. The host plant, organpipe cactus, exhibits extremes in temperature and pH in the same geographic region. Strains from Baja California, Mexico, possess a high frequency of Adh-F, whose product is heat and pH sensitive. The substrate in this region, agria cactus, has moderate temperature and pH extremes and contains relatively high concentrations of isopropanol. Isopropanol is presumable a selective agen favorable to Adh-F. The environmental heterogeneity that is proposed for maintaining the alleles at the alcohol dehydrogenase locus is the interaction of substrate alcohol content with temperature and pH. Substrates that do not contain appreciable amounts of isopropanol and are exposed to high temperatures and exhibit variable pH favor Adh-S, while substrates containing isopropanol and having moderate temperatures and pH favor Adh-F."}
{"id": "PMID:13370", "title": "Reconstitution of native human hemoglobin from separated globin chains and alloplex intermediates.", "content": "A complete experimental format is given for the reconstitution of human hemoglobin from the separated heme-free alpha- and beta-globin chains (alpha degrees, beta degrees) and hemin, by two alternative routes. Based on their oxygen binding properties, the reaction of the ferri-forms with reducing agent, and the response of the oxygen binding curves to pH variation and to the addition of the allosteric effector 2,3-diphosphoglycerate, the molecules are native. One reconstitution route uses direct addition of hemin to the separated globin chains with production of the separated subunits, which can then be recombined and reduced. This procedure occasions losses by precipitation in the heme-addition step except at high dilutions, and the yields are low. In the second pathway, either globin chain is mixed with the complementary untreated subunit to form the half-filled (with heme) intermediates, which combine stoichiometrically with hemin. No precipitation accompanies these reactions. For alpha-globin, the yield is about 50% because of incomplete combination with the heme-containing beta chain. For beta-globin, the yield is better than 70%. It is suggested that experiments intended to test either globin chain should use the second route in preparation for structural or functional comparisons with native hemoglobin.", "contents": "Reconstitution of native human hemoglobin from separated globin chains and alloplex intermediates. A complete experimental format is given for the reconstitution of human hemoglobin from the separated heme-free alpha- and beta-globin chains (alpha degrees, beta degrees) and hemin, by two alternative routes. Based on their oxygen binding properties, the reaction of the ferri-forms with reducing agent, and the response of the oxygen binding curves to pH variation and to the addition of the allosteric effector 2,3-diphosphoglycerate, the molecules are native. One reconstitution route uses direct addition of hemin to the separated globin chains with production of the separated subunits, which can then be recombined and reduced. This procedure occasions losses by precipitation in the heme-addition step except at high dilutions, and the yields are low. In the second pathway, either globin chain is mixed with the complementary untreated subunit to form the half-filled (with heme) intermediates, which combine stoichiometrically with hemin. No precipitation accompanies these reactions. For alpha-globin, the yield is about 50% because of incomplete combination with the heme-containing beta chain. For beta-globin, the yield is better than 70%. It is suggested that experiments intended to test either globin chain should use the second route in preparation for structural or functional comparisons with native hemoglobin."}
{"id": "PMID:13371", "title": "Effect of gangliosides and substrate analogues on the hydrolysis of nicotinamide adenine dinucleotide by choleragen.", "content": "Choleragen and its A protomer catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. NADase activity was inhibited by gangliosides GM1 (galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide), GM2 (N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide), GM3 (N-acetylneuraminyl-galactosylglucosylceramide), and GD1a (N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-E1N-acetylneuraminyl]-galactosylglucosylceramide). These gangliosides also increased the intensity of the tryptophanyl fluorescence of the isolated A protomer (lambda max = 328 nm). GM1 but not GM2, GM3, and GD1a caused a \"blue shift\" in the fluorescence spectrum of the B protomer. These results are consistent with other evidence that the specificity of GM1 as the choleragen receptor resides in its carbohydrate moiety. The NADase activity of choleragen was similar to that of diphtheria toxin previously described [J. Kandel, R. J. Collier & D. W. Chung (1974) J. Biol. Chem. 249, 2088-2097]. As with diphtheria toxin, analogues of NAD were inhibitory, adenine being the most effective. Significant inhibition was also noted with adenosine, AMP, ADP-ribose, nicotinamide, nicotinamide mononucleotide, and NADP. NADP was hydrolyzed only slowly by choleragen. In the NADase reaction catalyzed by diphtheria toxin, water serves as an acceptor for the ADP-ribose moiety of NAD in lieu of the natural acceptor molecule, which is elongation factor II (Kandel et al., 1974). It seems probable that the natural protein acceptor for ADP-ribose in the reaction catalyzed by choleragen is adenylate cyclase or a protein component of a cyclase complex that regulates enzymatic activity.", "contents": "Effect of gangliosides and substrate analogues on the hydrolysis of nicotinamide adenine dinucleotide by choleragen. Choleragen and its A protomer catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. NADase activity was inhibited by gangliosides GM1 (galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide), GM2 (N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide), GM3 (N-acetylneuraminyl-galactosylglucosylceramide), and GD1a (N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-E1N-acetylneuraminyl]-galactosylglucosylceramide). These gangliosides also increased the intensity of the tryptophanyl fluorescence of the isolated A protomer (lambda max = 328 nm). GM1 but not GM2, GM3, and GD1a caused a \"blue shift\" in the fluorescence spectrum of the B protomer. These results are consistent with other evidence that the specificity of GM1 as the choleragen receptor resides in its carbohydrate moiety. The NADase activity of choleragen was similar to that of diphtheria toxin previously described [J. Kandel, R. J. Collier & D. W. Chung (1974) J. Biol. Chem. 249, 2088-2097]. As with diphtheria toxin, analogues of NAD were inhibitory, adenine being the most effective. Significant inhibition was also noted with adenosine, AMP, ADP-ribose, nicotinamide, nicotinamide mononucleotide, and NADP. NADP was hydrolyzed only slowly by choleragen. In the NADase reaction catalyzed by diphtheria toxin, water serves as an acceptor for the ADP-ribose moiety of NAD in lieu of the natural acceptor molecule, which is elongation factor II (Kandel et al., 1974). It seems probable that the natural protein acceptor for ADP-ribose in the reaction catalyzed by choleragen is adenylate cyclase or a protein component of a cyclase complex that regulates enzymatic activity."}
{"id": "PMID:13372", "title": "31P nuclear magnetic resonance studies of Ehrlich ascites tumor cells.", "content": "High-resolution 31P nuclear magnetic resonance spectra at 145.7 MHz are reported for intact Ehrlich ascites tumor cells and their perchloric acid extracts. In the extracts it was possible to assign resonances to fructose 1,6-bisphosphates, dihydroxyacetone phosphate, ATP, ADP, AMP, Pi, NAD+, phosphorylcholine, glycero-3-phosphorylcholine, glycero-3-phosphorylethanolamine, and glyceraldehyde 3-phosphate from their chemical shifts, pH behavior, and spin couplings. All but glyceraldehyde 3-phosphate were observed and assigned in the intact cells. It was possible to show that the hydrolysis of fructose 1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate is in equilibrium, that the dihydroxyacetone phosphate leads to glyceraldehyde 3-phosphate reaction is not, and that in the intact cell without added oxygen or glucose the reaction 2ADP in equilibrium ATP + AMP is in equilibrium. From the known pH dependence of the Pi resonance it was possible to show that during aerobic or anerobic glycolysis the difference between intracellular and extracellular pH values was less than 0.2 pH units. Upon oxygenation the ATP concentration increased while the ADP concentration fell. Introducing deoxyglucose depleted the ATP and resulted in an AMP signal and one from deoxyglucose 6-phosphate, which is transported and phosphorylated but not catabolized.", "contents": "31P nuclear magnetic resonance studies of Ehrlich ascites tumor cells. High-resolution 31P nuclear magnetic resonance spectra at 145.7 MHz are reported for intact Ehrlich ascites tumor cells and their perchloric acid extracts. In the extracts it was possible to assign resonances to fructose 1,6-bisphosphates, dihydroxyacetone phosphate, ATP, ADP, AMP, Pi, NAD+, phosphorylcholine, glycero-3-phosphorylcholine, glycero-3-phosphorylethanolamine, and glyceraldehyde 3-phosphate from their chemical shifts, pH behavior, and spin couplings. All but glyceraldehyde 3-phosphate were observed and assigned in the intact cells. It was possible to show that the hydrolysis of fructose 1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate is in equilibrium, that the dihydroxyacetone phosphate leads to glyceraldehyde 3-phosphate reaction is not, and that in the intact cell without added oxygen or glucose the reaction 2ADP in equilibrium ATP + AMP is in equilibrium. From the known pH dependence of the Pi resonance it was possible to show that during aerobic or anerobic glycolysis the difference between intracellular and extracellular pH values was less than 0.2 pH units. Upon oxygenation the ATP concentration increased while the ADP concentration fell. Introducing deoxyglucose depleted the ATP and resulted in an AMP signal and one from deoxyglucose 6-phosphate, which is transported and phosphorylated but not catabolized."}
{"id": "PMID:13409", "title": "Influence of three short-chain peptides (alpha-MSH, MSH/ACTH 4-10, MIF-I on) dimensional attention.", "content": "Male, albino rats were treated with alpha-MSH, MSH/ACTH 4-10, MIF-I or a diluent control solution and then tested on a visual discrimination problem. Immediately after acquistion of the visual task the animals were tested with a spatial extradimensional shift problem. The animals treated with the MSH/ACTH 4-10 and MIF-I acquired the discrimination nonsignificantly faster than animals treated with alpha-MSH or a placebo. A subproblem analysis of the EDS behavior indicated that the peptides significantly improved performance probably by affecting attention.", "contents": "Influence of three short-chain peptides (alpha-MSH, MSH/ACTH 4-10, MIF-I on) dimensional attention. Male, albino rats were treated with alpha-MSH, MSH/ACTH 4-10, MIF-I or a diluent control solution and then tested on a visual discrimination problem. Immediately after acquistion of the visual task the animals were tested with a spatial extradimensional shift problem. The animals treated with the MSH/ACTH 4-10 and MIF-I acquired the discrimination nonsignificantly faster than animals treated with alpha-MSH or a placebo. A subproblem analysis of the EDS behavior indicated that the peptides significantly improved performance probably by affecting attention."}
{"id": "PMID:13410", "title": "Investigations on alpha-MSH and MIF-1 effects on cyclic AMP levels in rat brain.", "content": "It has been suggested that the peptides alpha-metanocyte stimulating hormone (alpha-MSH) and MSH-release inhibitory factor (MIF-1) may alter adenosine-3', 5'-cyclic monophosphate (cAMP) metabolism [13,26]. Normal and hypophysectomized (hypoxed) rats were administered saline (controls IP daily X 3), alpha-MSH (80 mug/kg IP daily X 3) or MIF-1 (1 or 10 mg/kg IP daily X 3) and sacrificed 30 min after the third injection in a focused microwave oven (1.5 KW; 2-3 sec). Various brain areas were then assayed for cAMP levels after each treatment. The occipital cortex area was the only area to show consistent changes in both normal and hypoxed rats after alpha-MSH treatment. These findings were replicated for the occipital cortex in a second group of normal and hypoxed rats which were similarly treated. The results suggest a correlation between the rise in cAMP found and reported changes in visual acuity and attention in rats and human after treatment with alpha-MSH [8,14, 23].", "contents": "Investigations on alpha-MSH and MIF-1 effects on cyclic AMP levels in rat brain. It has been suggested that the peptides alpha-metanocyte stimulating hormone (alpha-MSH) and MSH-release inhibitory factor (MIF-1) may alter adenosine-3', 5'-cyclic monophosphate (cAMP) metabolism [13,26]. Normal and hypophysectomized (hypoxed) rats were administered saline (controls IP daily X 3), alpha-MSH (80 mug/kg IP daily X 3) or MIF-1 (1 or 10 mg/kg IP daily X 3) and sacrificed 30 min after the third injection in a focused microwave oven (1.5 KW; 2-3 sec). Various brain areas were then assayed for cAMP levels after each treatment. The occipital cortex area was the only area to show consistent changes in both normal and hypoxed rats after alpha-MSH treatment. These findings were replicated for the occipital cortex in a second group of normal and hypoxed rats which were similarly treated. The results suggest a correlation between the rise in cAMP found and reported changes in visual acuity and attention in rats and human after treatment with alpha-MSH [8,14, 23]."}
{"id": "PMID:13411", "title": "Possible association of increased rat behavioral effects and increased striatal dopamine and norepinephrine levels during the DOPA-potentiation test.", "content": "Previous reports have indicated that alpha-MSH release inhibiting hormone (MIF-1) increased the behavior occurring as a result of the dihydroxyphenylalanine (DOPA) potentiation test [3,7]. This study was undertaken to see whether dopamine (DA) or norepinephrine (NE) levels likewise increased in the test animals. The DOPA potentiation test was performed as follows: 2-4 hr before behavior measurement, 40 mg/kg of the monoamine oxidase inhibitor pargyline HCl was given orally. Two hr later this was followed by the intraperitoneal (IP) injection of MIF-1 at doses of 0.1, 0.3 or 1.0 mg/kg. Behavioral measurement was begun after the IP injection of 200 mg/kg of dl-DOPA 1-2 hr after the MIF-1. The parameters included social interaction, aggressiveness, fighting, ataxia, jumping, defecation, urination and salivation. The animals were beheaded while the behavior was still increased and the striatal area removed, placed in aluminum foil, and kept at -50 degrees C until assayed. In general, especially among the younger animals, a significant correlation (p=0.05 to p=0.01) was found between the increased behavioral responses to MIF-I and the rise in DA. Because of a few exceptions to this correlation the possibility is suggested that MIF-I might also affect behavior by acting directly on the postsynaptic membrane thus bypassing any change in NE or DA which is known to increase cycli AMP in the striatum.", "contents": "Possible association of increased rat behavioral effects and increased striatal dopamine and norepinephrine levels during the DOPA-potentiation test. Previous reports have indicated that alpha-MSH release inhibiting hormone (MIF-1) increased the behavior occurring as a result of the dihydroxyphenylalanine (DOPA) potentiation test [3,7]. This study was undertaken to see whether dopamine (DA) or norepinephrine (NE) levels likewise increased in the test animals. The DOPA potentiation test was performed as follows: 2-4 hr before behavior measurement, 40 mg/kg of the monoamine oxidase inhibitor pargyline HCl was given orally. Two hr later this was followed by the intraperitoneal (IP) injection of MIF-1 at doses of 0.1, 0.3 or 1.0 mg/kg. Behavioral measurement was begun after the IP injection of 200 mg/kg of dl-DOPA 1-2 hr after the MIF-1. The parameters included social interaction, aggressiveness, fighting, ataxia, jumping, defecation, urination and salivation. The animals were beheaded while the behavior was still increased and the striatal area removed, placed in aluminum foil, and kept at -50 degrees C until assayed. In general, especially among the younger animals, a significant correlation (p=0.05 to p=0.01) was found between the increased behavioral responses to MIF-I and the rise in DA. Because of a few exceptions to this correlation the possibility is suggested that MIF-I might also affect behavior by acting directly on the postsynaptic membrane thus bypassing any change in NE or DA which is known to increase cycli AMP in the striatum."}
{"id": "PMID:13412", "title": "Effects of L-prolyl-L-leucyl-glycine amide (MIF-I) on dopaminergic neurons.", "content": "In an attempt to determine the mechanism of action of L-proly-L-leucyl-glycine amide (MIF-I) in the treatment of Parkinson's disease, various parameters of dopaminergic neuronal function were studied in rats. It was found that the active uptake of 3H-dopamine (3H-DA) by synaptosome-rich homogenates of the striatum of rats treated with MIF-I (1 mg/kg IP X 3, 24 hr intervals) was unaltered 1 hr after final treatment with MIF-I. Also, neither tyrosine hydroxylase nor dopa decarboxylase activity was altered in the striatum and substantia nigra of rats treated with MIF-I (20 mg/kg IP X 3, 24 hr intervals). Thus, vital functional processes associated with dopaminergic neurons apparently are not altered by MIF-I under the conditions studied. These findings illustrate the importance of concurrent DOPA administration in observing an effect of MIF-I on dopaminergic neuronal function.", "contents": "Effects of L-prolyl-L-leucyl-glycine amide (MIF-I) on dopaminergic neurons. In an attempt to determine the mechanism of action of L-proly-L-leucyl-glycine amide (MIF-I) in the treatment of Parkinson's disease, various parameters of dopaminergic neuronal function were studied in rats. It was found that the active uptake of 3H-dopamine (3H-DA) by synaptosome-rich homogenates of the striatum of rats treated with MIF-I (1 mg/kg IP X 3, 24 hr intervals) was unaltered 1 hr after final treatment with MIF-I. Also, neither tyrosine hydroxylase nor dopa decarboxylase activity was altered in the striatum and substantia nigra of rats treated with MIF-I (20 mg/kg IP X 3, 24 hr intervals). Thus, vital functional processes associated with dopaminergic neurons apparently are not altered by MIF-I under the conditions studied. These findings illustrate the importance of concurrent DOPA administration in observing an effect of MIF-I on dopaminergic neuronal function."}
{"id": "PMID:13413", "title": "Neurochemical responses of mice to ACTH and lysine vasopressin.", "content": "Subcutaneous administration of ACTH 1-24 to mice increased the incorporation of [3H]lysine into brain and liver proteins, an effect which resembled that due to footshock. Corticosterone administration did not mimic these effects. ACTH 4-10 increased the [3H]lysine incorporation into brain or liver. These results are consistent with ACTH mediating the effects of footshock. However, dexamethasone decreased the brain responses to both footshock and ACTH, but while the liver response to ACTH was blocked, the footshock response was only diminished. This suggests a neural component in the response of the liver and possibly the brain. Intraventricular administration of ACTH 1-24 or ACTH 4-10 (D-phe), but not ACTH 4-10, increased [3H]lysine incorporation into brain protein. These neurochemical responses parallelled a distinctive pattern of behavior characterized by stretching, yawning and excessive grooming. Treatment for 3 days with long-acting preparations of ACTH 4-10, ACTH 4-10 (D-phe) or ACTH 1-24 increased the conversion of [3H]tyrosine into dopamine but not norepinephrine, alpha-MSH, beta-MSH or LVP had no such effect. Similar treatment with ACTH 4-10 or ACTH 1-24 increased striatal tyrosine hydroxylase activity measured in vitro, but did not significantly alter the enzyme activity from other brain regions. We conclude that ACTH peptides can stimulate protein and dopamine metabolism in mouse brain and that LVP has no such effects.", "contents": "Neurochemical responses of mice to ACTH and lysine vasopressin. Subcutaneous administration of ACTH 1-24 to mice increased the incorporation of [3H]lysine into brain and liver proteins, an effect which resembled that due to footshock. Corticosterone administration did not mimic these effects. ACTH 4-10 increased the [3H]lysine incorporation into brain or liver. These results are consistent with ACTH mediating the effects of footshock. However, dexamethasone decreased the brain responses to both footshock and ACTH, but while the liver response to ACTH was blocked, the footshock response was only diminished. This suggests a neural component in the response of the liver and possibly the brain. Intraventricular administration of ACTH 1-24 or ACTH 4-10 (D-phe), but not ACTH 4-10, increased [3H]lysine incorporation into brain protein. These neurochemical responses parallelled a distinctive pattern of behavior characterized by stretching, yawning and excessive grooming. Treatment for 3 days with long-acting preparations of ACTH 4-10, ACTH 4-10 (D-phe) or ACTH 1-24 increased the conversion of [3H]tyrosine into dopamine but not norepinephrine, alpha-MSH, beta-MSH or LVP had no such effect. Similar treatment with ACTH 4-10 or ACTH 1-24 increased striatal tyrosine hydroxylase activity measured in vitro, but did not significantly alter the enzyme activity from other brain regions. We conclude that ACTH peptides can stimulate protein and dopamine metabolism in mouse brain and that LVP has no such effects."}
{"id": "PMID:13414", "title": "Peptides readily penetrate the blood-brain barrier: uptake of peptides by synaptosomes is passive.", "content": "The intracarotid artery quick injection technique of Oldendorf was utilized to determine the Brain Uptake Index (BUI) of radio-labeled peptides in comparison with 3H2O or 14C-antipyrine as counterlabels. The normalized BUI values for 3H-MIF-I, 3H-alpha-MSH and 14C-AVP were 13.7, 9.6 and 13.0 respectively at 15 sec after injection consistent with their having readily penetrated the blood-brain barrier. The BUI values were similar, though somewhat increased, at 10 min postinjection consistent with their ready exit across the blood-brain barrier. At 15 sec after injection 0.5+/-0.1%/g brain of the originally injected peptide label was recovered; and 0.1+/-0.2%/g brain was recovered after 10 min. The label was distributed uniformly in the major brain regions at both times. However, the percentage of the originally injected label/g of pineal and pituitary gland tissue was 10-20 X increased as compared with the major brain regions as would be expected by their location outside the blood-brain barrier. The in vitro uptake of the radio-labeled peptides by synaptosomes prepared from the whole brain and the major brain regions was passive; it was not temperature dependent, nor was it Na+ dependent. However, the binding of the three peptides by the synaptosomes varied considerably: AVP greater than MSH greater MIF: 50 greater than 5 greater 1. The penetratin of the blood-brain barrier by the three peptides is consistent with their having CNS effects.", "contents": "Peptides readily penetrate the blood-brain barrier: uptake of peptides by synaptosomes is passive. The intracarotid artery quick injection technique of Oldendorf was utilized to determine the Brain Uptake Index (BUI) of radio-labeled peptides in comparison with 3H2O or 14C-antipyrine as counterlabels. The normalized BUI values for 3H-MIF-I, 3H-alpha-MSH and 14C-AVP were 13.7, 9.6 and 13.0 respectively at 15 sec after injection consistent with their having readily penetrated the blood-brain barrier. The BUI values were similar, though somewhat increased, at 10 min postinjection consistent with their ready exit across the blood-brain barrier. At 15 sec after injection 0.5+/-0.1%/g brain of the originally injected peptide label was recovered; and 0.1+/-0.2%/g brain was recovered after 10 min. The label was distributed uniformly in the major brain regions at both times. However, the percentage of the originally injected label/g of pineal and pituitary gland tissue was 10-20 X increased as compared with the major brain regions as would be expected by their location outside the blood-brain barrier. The in vitro uptake of the radio-labeled peptides by synaptosomes prepared from the whole brain and the major brain regions was passive; it was not temperature dependent, nor was it Na+ dependent. However, the binding of the three peptides by the synaptosomes varied considerably: AVP greater than MSH greater MIF: 50 greater than 5 greater 1. The penetratin of the blood-brain barrier by the three peptides is consistent with their having CNS effects."}
{"id": "PMID:13415", "title": "Neurologically active peptides.", "content": "This paper reviews recent evidence that a number of small peptides found in the brain are active in the central nervous system and behaviorally. Attention is focused on MSH/ACTH 4-10, alpha- and beta-MSH, and the prohormone beta-LPH, as they produce a syndrome of yawning and stretching. Studies with substance P and mainly with MIF-I are also reviewed. It is shown that substance P is an excitatory transmitter or modulator in the dorsal spinal cord with that MIF-I has antiparkinson properties. It is concluded that many polypeptides have direct actions on the central nervous system independent of their neuroendocrine properties.", "contents": "Neurologically active peptides. This paper reviews recent evidence that a number of small peptides found in the brain are active in the central nervous system and behaviorally. Attention is focused on MSH/ACTH 4-10, alpha- and beta-MSH, and the prohormone beta-LPH, as they produce a syndrome of yawning and stretching. Studies with substance P and mainly with MIF-I are also reviewed. It is shown that substance P is an excitatory transmitter or modulator in the dorsal spinal cord with that MIF-I has antiparkinson properties. It is concluded that many polypeptides have direct actions on the central nervous system independent of their neuroendocrine properties."}
{"id": "PMID:13416", "title": "Hypothalamic releasing factors: physiological evidence for a regulatory action on central neurons and pathways for their distribution in brain.", "content": "Recent observations based on single cell recordings obtained in various areas of the brain indicate that TRH, LH-RH and somatostatin have potent effects on the activity of central neurons. There is also electrophysiological evidence for the existence of a system of hypothalamic tuberoinfundibular neurons with widespread extrahypothalamic connections. These connections may indicate possible pathways for the observed widespread distribution of these peptides in the brain. These findings, coupled with behavioral studies and subcellular localization data support the postulate that hypothalamic peptides may have an important role inthe modulation of central neuronal activity.", "contents": "Hypothalamic releasing factors: physiological evidence for a regulatory action on central neurons and pathways for their distribution in brain. Recent observations based on single cell recordings obtained in various areas of the brain indicate that TRH, LH-RH and somatostatin have potent effects on the activity of central neurons. There is also electrophysiological evidence for the existence of a system of hypothalamic tuberoinfundibular neurons with widespread extrahypothalamic connections. These connections may indicate possible pathways for the observed widespread distribution of these peptides in the brain. These findings, coupled with behavioral studies and subcellular localization data support the postulate that hypothalamic peptides may have an important role inthe modulation of central neuronal activity."}
{"id": "PMID:13417", "title": "MIF, TRH, and simian social and motor behavior.", "content": "MSH-release-inhibiting factor (MIF) and thyrotropin-releasing hormone (TRH) both have been reported to modify mood and activity in man. These two hypothalamic peptides were given intramuscularly across a 1000-fold dose range to 5 juvenile male M. nemestrina monkeys living in a social group. Motor activity was recorded automatically, and an observer counted various social behaviors. MIF increased motor activity for up to 11 hr. It decreased quiet foraging behavior, but did not change behaviors of social interaction. TRH did not stimulate motor behavior; high doses strongly suppressed it and produced apparent somatic distress. TRH increased behaviors of quiet rest and association and decreased environment exploration and low-intensity dominance behaviors. The lowest dose of TRH increased social play. Two monkeys showed repetitive, stereotyped behaviors even in baseline observations, and certain doses of TRH and MIF may have increased the frequency of these behaviors.", "contents": "MIF, TRH, and simian social and motor behavior. MSH-release-inhibiting factor (MIF) and thyrotropin-releasing hormone (TRH) both have been reported to modify mood and activity in man. These two hypothalamic peptides were given intramuscularly across a 1000-fold dose range to 5 juvenile male M. nemestrina monkeys living in a social group. Motor activity was recorded automatically, and an observer counted various social behaviors. MIF increased motor activity for up to 11 hr. It decreased quiet foraging behavior, but did not change behaviors of social interaction. TRH did not stimulate motor behavior; high doses strongly suppressed it and produced apparent somatic distress. TRH increased behaviors of quiet rest and association and decreased environment exploration and low-intensity dominance behaviors. The lowest dose of TRH increased social play. Two monkeys showed repetitive, stereotyped behaviors even in baseline observations, and certain doses of TRH and MIF may have increased the frequency of these behaviors."}
{"id": "PMID:13418", "title": "Clinical investigations for emotional effects of neuropeptide hormones.", "content": "After the demonstration that hypothalamic peptides can have a direct effect on the central nervous system, a series of studies was initiated to investigate the hypothesis that hypothalamic peptides could have an effect on emotions and affect. TRH was administered to 6 patients with endogenous depressions in a double-blind, cross-over design with transient improvements in the mental depression of 4 of the 6 patients. In a second study involving 8 seriously depressed patients given 1000 mug of TRH for 10 days, no significant antidepressant effect of TRH was observed. In a pilot, double-blind study of 18 women with endogenous depressions, the group receiving MIF-1 60 mg per day in a single daily dose for 6 days responded better than the placebo group, which in turn responded better than the group receiving MIF-1 150 mg per day. In a second, double-blind study testing MIF-1 in endogenous depressions, 5 patients met the criteria for substantial improvement out of a total of 8 receiving MIF-1 75 mg per day. In contrast, only one patient met these criteria in each of the remaining 2 groups, consisting of 10 patients receiving MIF-1 750 mg per day and 5 patients receiving placebo. Finally, 6 men complaining of decreased libido and/or potency were given intravenous injections of LHRH 700 mug or saline once daily for 3 consecutive days per week in a double-blind, cross-over design. In addition, 3 men were given much higher doses of LHRH in a single-blinded study. No substantial effect on libido or sexual performance was observed.", "contents": "Clinical investigations for emotional effects of neuropeptide hormones. After the demonstration that hypothalamic peptides can have a direct effect on the central nervous system, a series of studies was initiated to investigate the hypothesis that hypothalamic peptides could have an effect on emotions and affect. TRH was administered to 6 patients with endogenous depressions in a double-blind, cross-over design with transient improvements in the mental depression of 4 of the 6 patients. In a second study involving 8 seriously depressed patients given 1000 mug of TRH for 10 days, no significant antidepressant effect of TRH was observed. In a pilot, double-blind study of 18 women with endogenous depressions, the group receiving MIF-1 60 mg per day in a single daily dose for 6 days responded better than the placebo group, which in turn responded better than the group receiving MIF-1 150 mg per day. In a second, double-blind study testing MIF-1 in endogenous depressions, 5 patients met the criteria for substantial improvement out of a total of 8 receiving MIF-1 75 mg per day. In contrast, only one patient met these criteria in each of the remaining 2 groups, consisting of 10 patients receiving MIF-1 750 mg per day and 5 patients receiving placebo. Finally, 6 men complaining of decreased libido and/or potency were given intravenous injections of LHRH 700 mug or saline once daily for 3 consecutive days per week in a double-blind, cross-over design. In addition, 3 men were given much higher doses of LHRH in a single-blinded study. No substantial effect on libido or sexual performance was observed."}
{"id": "PMID:13421", "title": "The structure of a spherical plant virus (bromegrass mosaic virus) established by neutron diffraction.", "content": "The localization of the RNA in a spherical plant virus is established by neutron diffraction. For BMV, this localization is different at low pH than it is at high pH (swollen virus).", "contents": "The structure of a spherical plant virus (bromegrass mosaic virus) established by neutron diffraction. The localization of the RNA in a spherical plant virus is established by neutron diffraction. For BMV, this localization is different at low pH than it is at high pH (swollen virus)."}
{"id": "PMID:13422", "title": "Assembly of a spherical plant virus.", "content": "The conditions previously reported as necessary for the reassembly of spherical viruses have been distinctly unphysiological and such reassembly cannot be related directly to the in vivo reaction. Mild conditions for the in vitro reassembly of cowpea chlorotic mottle virus (CCMV) from its isolated components have now been described (Adolph & Butler 1975) and the reassembled virus characterized. This reassembly involved the co-aggregation of the RNA and protein around neutrality and at ionic strength 0.2, giving yields of 70% encapsidation at pH 6.0. The reaction was independent of temperature over the range 5-25 degrees C and did not require the presence of Mg2+ ions. The reassembled virus shows a stability similar to that of native CCMV, with the same change in sedimentation coefficient around pH 6.5. The molecular mass and buoyant density in CsCl are also the same as those of native CCMV, while the electron microscope reveals a surface morphology on the reassembled particles like that on native CCMV. Analysis of the number-average, mass-average, and Z-average molecular masses of the purified protein at both pH 6.0 and pH 7.5 suggests that the active unit for reassembly is a dimer of the protein subunit.", "contents": "Assembly of a spherical plant virus. The conditions previously reported as necessary for the reassembly of spherical viruses have been distinctly unphysiological and such reassembly cannot be related directly to the in vivo reaction. Mild conditions for the in vitro reassembly of cowpea chlorotic mottle virus (CCMV) from its isolated components have now been described (Adolph & Butler 1975) and the reassembled virus characterized. This reassembly involved the co-aggregation of the RNA and protein around neutrality and at ionic strength 0.2, giving yields of 70% encapsidation at pH 6.0. The reaction was independent of temperature over the range 5-25 degrees C and did not require the presence of Mg2+ ions. The reassembled virus shows a stability similar to that of native CCMV, with the same change in sedimentation coefficient around pH 6.5. The molecular mass and buoyant density in CsCl are also the same as those of native CCMV, while the electron microscope reveals a surface morphology on the reassembled particles like that on native CCMV. Analysis of the number-average, mass-average, and Z-average molecular masses of the purified protein at both pH 6.0 and pH 7.5 suggests that the active unit for reassembly is a dimer of the protein subunit."}
{"id": "PMID:13423", "title": "Nature and specificity of the RNA-protein interaction in the case of the tymoviruses.", "content": "Dissociation-reassociation experiments performed with turnip yellow mosaic virus in the presence of various RNAs and polynucleotides were used to investigate the degree of specificity and the contribution of the associated RNA moiety to the stability of TYMV. The results emphasize the importance of strategic cytosine residues spread along the RNA chain. Some insight into the contribution of the protein could be gained from comparison of TYMV and eggplant mosaic virus (EMV), a virus similar to TYMV although its top component contains low molecular mass RNA's able to bind various amino acids. Hydrophobic interactions between protein subunits are less important in EMV than in TYMV, and artificial capsids could be obtained from dissociated EMV coat protein. Whether the capsid is or is not the precursor of the virion in tymovirus morphogenesis is discussed.", "contents": "Nature and specificity of the RNA-protein interaction in the case of the tymoviruses. Dissociation-reassociation experiments performed with turnip yellow mosaic virus in the presence of various RNAs and polynucleotides were used to investigate the degree of specificity and the contribution of the associated RNA moiety to the stability of TYMV. The results emphasize the importance of strategic cytosine residues spread along the RNA chain. Some insight into the contribution of the protein could be gained from comparison of TYMV and eggplant mosaic virus (EMV), a virus similar to TYMV although its top component contains low molecular mass RNA's able to bind various amino acids. Hydrophobic interactions between protein subunits are less important in EMV than in TYMV, and artificial capsids could be obtained from dissociated EMV coat protein. Whether the capsid is or is not the precursor of the virion in tymovirus morphogenesis is discussed."}
{"id": "PMID:13424", "title": "A study of the states of aggregation of alfalfa mosaic virus protein.", "content": "The states of aggregation of alfalfa mosaic virus (AMV) protein have been characterized by sedimentation velocity experiments and electron microscopy. The main association product is a spherical particle with an s value of about 30S. It is highly likely that the assembly of this particle starts with dimers of the 25000 molecular mass unit resulting in an icosahedral particle made of 30 dimers. No intermediate aggregation products have been detected. The clustering pattern of the protein in the cylindrical part of the AMV capsid favours the concept of dimers as the active assembling units.", "contents": "A study of the states of aggregation of alfalfa mosaic virus protein. The states of aggregation of alfalfa mosaic virus (AMV) protein have been characterized by sedimentation velocity experiments and electron microscopy. The main association product is a spherical particle with an s value of about 30S. It is highly likely that the assembly of this particle starts with dimers of the 25000 molecular mass unit resulting in an icosahedral particle made of 30 dimers. No intermediate aggregation products have been detected. The clustering pattern of the protein in the cylindrical part of the AMV capsid favours the concept of dimers as the active assembling units."}
{"id": "PMID:13425", "title": "Packaging of genomes in bacteriophages: a comparison of ssRNA bacteriophages and dsDNA bacteriophages.", "content": "In complex DNA bacteriophages like lambda, T4, T7, P22, P2, the DNA is packaged into a preformed precursor particle which sometimes has a smaller size and often a shape different from that of the phage head. This packaging mechanism is different from the one suggested for the RNA phages, according to which RNA nucleates the shell formation. The different mechanisms could be understood by comparing the genomes to be packaged: single stranded fII RNA has a very compact structure with high helix content. It might easily form quasispherical structures in solution (as seen in the electron microscope by Thach & Thach (1973)) around which the capsid could assemble. Double stranded phage DNA, on the other hand, is a rigid molecule which occupies a large volume in solution and has to be concentrated 15-fold during packaging into the preformed capsid, and the change in the capsid structure observed hereby might provide the necessary DNA condensation energy.", "contents": "Packaging of genomes in bacteriophages: a comparison of ssRNA bacteriophages and dsDNA bacteriophages. In complex DNA bacteriophages like lambda, T4, T7, P22, P2, the DNA is packaged into a preformed precursor particle which sometimes has a smaller size and often a shape different from that of the phage head. This packaging mechanism is different from the one suggested for the RNA phages, according to which RNA nucleates the shell formation. The different mechanisms could be understood by comparing the genomes to be packaged: single stranded fII RNA has a very compact structure with high helix content. It might easily form quasispherical structures in solution (as seen in the electron microscope by Thach & Thach (1973)) around which the capsid could assemble. Double stranded phage DNA, on the other hand, is a rigid molecule which occupies a large volume in solution and has to be concentrated 15-fold during packaging into the preformed capsid, and the change in the capsid structure observed hereby might provide the necessary DNA condensation energy."}
{"id": "PMID:13426", "title": "Studies on the maturation of the head of bacteriophage T4.", "content": "The presentation focuses on the structural rearrangements of the subunits and the processing of the various protein constituents which accompany the maturation events of the head of bacteriophage T4. The major features of the maturation steps of the head are the following: (a) the viral DNA is pulled into an empty head in a series of events; (b) cleavage of two core proteins, P22 (mol. mass = 31000), to small fragments and the internal protein IPIII (mol. mass = 23000) to IPIII (mol. mass = 21000) appears to be intimately linked to the DNA packaging event, whereas the cleavage of the major head protein of the viral coat, P23 (mol. mass = 55000), to P23 (mol. mass = 45000) precedes the DNA packaging event. Recently, we have obtained information about the mechanism by which the viral DNA is pulled into a preformed empty head. Our evidence suggests that the DNA becomes attached to the inside of the empty head and is subsequently collapsed in the interior by the so-called internal peptides. These are highly acidic and derived from a large precursor protein by cleavage.", "contents": "Studies on the maturation of the head of bacteriophage T4. The presentation focuses on the structural rearrangements of the subunits and the processing of the various protein constituents which accompany the maturation events of the head of bacteriophage T4. The major features of the maturation steps of the head are the following: (a) the viral DNA is pulled into an empty head in a series of events; (b) cleavage of two core proteins, P22 (mol. mass = 31000), to small fragments and the internal protein IPIII (mol. mass = 23000) to IPIII (mol. mass = 21000) appears to be intimately linked to the DNA packaging event, whereas the cleavage of the major head protein of the viral coat, P23 (mol. mass = 55000), to P23 (mol. mass = 45000) precedes the DNA packaging event. Recently, we have obtained information about the mechanism by which the viral DNA is pulled into a preformed empty head. Our evidence suggests that the DNA becomes attached to the inside of the empty head and is subsequently collapsed in the interior by the so-called internal peptides. These are highly acidic and derived from a large precursor protein by cleavage."}
{"id": "PMID:13427", "title": "Assembly of tobacco mosaic virus.", "content": "The assembly of tobacco mosaic virus requires the presence of a particular protein aggregate, the disk. During the nucleation, a specific region of the RNA interacts with a single disk, to bring about a necessarily cooperative transition from the paired two-layer structure to a short segment of nucleo-protein helix. There is a high selectivity for this region of the TMV RNA, because of the many nucleotides bound at once, and other nucleotide sequences appear only to bind by a different mechanism. Elongation of the nucleated rods can continue with either further disks or the less aggregated 'A-protein' as the protein source, but the continued cooperativity inherent with disks would have some advantages. The rates of the two processes have been separately determined and growth is faster when disks are still present. New experiments show that the breakdown of disks to yield A-protein is relatively slow and it is concluded that virus growth from disks could not proceed through a prior breakdown in solution, but must involve the direct interaction of the disk with the growing nucleoprotein rod. The detailed mechanism of disk addition is not understood but it may involve a directed breakdown, since there is also evidence for the existence of a non-equilibrium form of A-protein which has aggregation kinetics distinct from those of equilibrium A-protein. Some implications for the general assembly pathways of viruses both of the specificity and of the assembly/disassembly cycle during the viral infection are considered.", "contents": "Assembly of tobacco mosaic virus. The assembly of tobacco mosaic virus requires the presence of a particular protein aggregate, the disk. During the nucleation, a specific region of the RNA interacts with a single disk, to bring about a necessarily cooperative transition from the paired two-layer structure to a short segment of nucleo-protein helix. There is a high selectivity for this region of the TMV RNA, because of the many nucleotides bound at once, and other nucleotide sequences appear only to bind by a different mechanism. Elongation of the nucleated rods can continue with either further disks or the less aggregated 'A-protein' as the protein source, but the continued cooperativity inherent with disks would have some advantages. The rates of the two processes have been separately determined and growth is faster when disks are still present. New experiments show that the breakdown of disks to yield A-protein is relatively slow and it is concluded that virus growth from disks could not proceed through a prior breakdown in solution, but must involve the direct interaction of the disk with the growing nucleoprotein rod. The detailed mechanism of disk addition is not understood but it may involve a directed breakdown, since there is also evidence for the existence of a non-equilibrium form of A-protein which has aggregation kinetics distinct from those of equilibrium A-protein. Some implications for the general assembly pathways of viruses both of the specificity and of the assembly/disassembly cycle during the viral infection are considered."}
{"id": "PMID:13428", "title": "Tobacco rattle virus RNA-protein interactions.", "content": "For the purpose of attempting to generalize the rules concerning morphogenesis of helical viruses, the in vitro reconstitution of the CAM strain of TRV was studied. The conditions for reconstitution and the importance of the aggregation state of the protein for initiation and elongation are compared with those of TMV. The initiation step consisting of the binding of RNA with the 36S disk of protein was easily accomplished. The polarity and the specificity of encapsidation of TRV RNA by homologous and heterologous viral protein is discussed.", "contents": "Tobacco rattle virus RNA-protein interactions. For the purpose of attempting to generalize the rules concerning morphogenesis of helical viruses, the in vitro reconstitution of the CAM strain of TRV was studied. The conditions for reconstitution and the importance of the aggregation state of the protein for initiation and elongation are compared with those of TMV. The initiation step consisting of the binding of RNA with the 36S disk of protein was easily accomplished. The polarity and the specificity of encapsidation of TRV RNA by homologous and heterologous viral protein is discussed."}
{"id": "PMID:13429", "title": "Assembly of flexuous plant viruses and their proteins.", "content": "Recent experiments on the disassembly and assembly of some flexuous plant viruses and their proteins are described. The properties of reconstituted potato virus X and those of assembled potato virus Y protein are considered as well as the suitability of other flexuous viruses for reconstitution studies.", "contents": "Assembly of flexuous plant viruses and their proteins. Recent experiments on the disassembly and assembly of some flexuous plant viruses and their proteins are described. The properties of reconstituted potato virus X and those of assembled potato virus Y protein are considered as well as the suitability of other flexuous viruses for reconstitution studies."}
{"id": "PMID:13430", "title": "Specific encapsidation of fragments of TMV RNA.", "content": "The in vitro reconstitution of tobacco mosaic virus (TMV) is initiated by the binding of a disk of TMV protein to the 'disk recognition site', a region of the RNA chain at or near the 5'-terminus for which the disk has special affinity. In order to gain insight into the recognition process, we have studied the ability of disks to encapsidate short RNA fragments produced by partial pancreatic or T1 RNase digestion of TMV RNA. The disk is capable of dicriminating among such fragments, encapsidating only a few of the many present in the digest. The products of encapsidation are short nucleoprotein rods of the same diameter as TMV and of length proportional to that of the encapsidated RNA fragment. The particles differ from TMV, however, in one significant aspect (apart from their length): they possess rings of RNA-free protein at one or both extremities of the rod. In the case of T1 RNase digestion the principal encapsidated fragments were fragments T1 (105 nucleotides) and a family of smaller fragments containing elements of the same sequence. Partial digestion with pancreatic RNase generated only one major fragment (fragment P1; 150 nucleotides) with affinity for the disk. Fragment T1 has been sequenced and shown to represent a portion of the coat protein cistron. Fragment P1 has been partially sequenced but its function is not yet known. Several lines of evidence indicate that fragment T1 is not the disk recognition site. The portion of the TMV RNA chain from which fragment P1 is derived, on the other hand, is encapsidated early in the reconstitution process; thus fragment P1 may contain the disk recognition site. Fragment T1 and fragment P1 both have purine-rich and cytosine-poor sequences near their termini. In addition, fragment T1, and possibly fragment P1, possess a periodicity of order three in purine residues. It seems likely that one or both of the aforesaid properties are largely responsible for the affinity of these fragments for the disk.", "contents": "Specific encapsidation of fragments of TMV RNA. The in vitro reconstitution of tobacco mosaic virus (TMV) is initiated by the binding of a disk of TMV protein to the 'disk recognition site', a region of the RNA chain at or near the 5'-terminus for which the disk has special affinity. In order to gain insight into the recognition process, we have studied the ability of disks to encapsidate short RNA fragments produced by partial pancreatic or T1 RNase digestion of TMV RNA. The disk is capable of dicriminating among such fragments, encapsidating only a few of the many present in the digest. The products of encapsidation are short nucleoprotein rods of the same diameter as TMV and of length proportional to that of the encapsidated RNA fragment. The particles differ from TMV, however, in one significant aspect (apart from their length): they possess rings of RNA-free protein at one or both extremities of the rod. In the case of T1 RNase digestion the principal encapsidated fragments were fragments T1 (105 nucleotides) and a family of smaller fragments containing elements of the same sequence. Partial digestion with pancreatic RNase generated only one major fragment (fragment P1; 150 nucleotides) with affinity for the disk. Fragment T1 has been sequenced and shown to represent a portion of the coat protein cistron. Fragment P1 has been partially sequenced but its function is not yet known. Several lines of evidence indicate that fragment T1 is not the disk recognition site. The portion of the TMV RNA chain from which fragment P1 is derived, on the other hand, is encapsidated early in the reconstitution process; thus fragment P1 may contain the disk recognition site. Fragment T1 and fragment P1 both have purine-rich and cytosine-poor sequences near their termini. In addition, fragment T1, and possibly fragment P1, possess a periodicity of order three in purine residues. It seems likely that one or both of the aforesaid properties are largely responsible for the affinity of these fragments for the disk."}
{"id": "PMID:13431", "title": "The region of tobacco mosaic virus RNA involved in the nucleation of assembly.", "content": "The interaction of TMV RNA with the disk aggregate of TMV protein at the initiation of assembly has been studied by using the techniques of RNA sequencing. The 5' end group has been identified, and shown not to be protected in the early stages of assembly from accessibility to nuclease digestion. A population of RNA fragments of average length 250 nucleotides, originating from a unique region of TMV RNA, is encapsidated by limited assembly, and sufficient sequence information is available to identify certain unusual features. The protected region does not contain highly reiterated simple repeating sequences, but may contain more complicated repeats. The length and complexity of the nucleation region may reflect adaptation to the efficient mediation of the conformational change from disk to helix of TMV protein, besides a requirement for binding to the disk, and this may be an important part of the mechanism of specificity in the nucleation of assembly.", "contents": "The region of tobacco mosaic virus RNA involved in the nucleation of assembly. The interaction of TMV RNA with the disk aggregate of TMV protein at the initiation of assembly has been studied by using the techniques of RNA sequencing. The 5' end group has been identified, and shown not to be protected in the early stages of assembly from accessibility to nuclease digestion. A population of RNA fragments of average length 250 nucleotides, originating from a unique region of TMV RNA, is encapsidated by limited assembly, and sufficient sequence information is available to identify certain unusual features. The protected region does not contain highly reiterated simple repeating sequences, but may contain more complicated repeats. The length and complexity of the nucleation region may reflect adaptation to the efficient mediation of the conformational change from disk to helix of TMV protein, besides a requirement for binding to the disk, and this may be an important part of the mechanism of specificity in the nucleation of assembly."}
{"id": "PMID:13432", "title": "Structure and assembly of phage phi29.", "content": "Bacteriophage phi29 is a small, morphologically complex, virus with a DNA of molecular mass 12 X 10(6). The most likely structure of the head of phi29 consists of two fivefold symmetric end-caps based on T = 1 icosahedral symmetry, separated by an equatorial row of 5 hexamers. The eighteen genes identified in phi29 genome have been mapped and, in some cases, the gene products have been identified. Five linked genes, four coding for structural proteins (G, A, E, H) and one coding for a non-structural protein (J), are essential to determine the normal shape of the capsid. Protein pJ may be a scaffolding protein. An account of the effects of mutations in phi29 genes is given.", "contents": "Structure and assembly of phage phi29. Bacteriophage phi29 is a small, morphologically complex, virus with a DNA of molecular mass 12 X 10(6). The most likely structure of the head of phi29 consists of two fivefold symmetric end-caps based on T = 1 icosahedral symmetry, separated by an equatorial row of 5 hexamers. The eighteen genes identified in phi29 genome have been mapped and, in some cases, the gene products have been identified. Five linked genes, four coding for structural proteins (G, A, E, H) and one coding for a non-structural protein (J), are essential to determine the normal shape of the capsid. Protein pJ may be a scaffolding protein. An account of the effects of mutations in phi29 genes is given."}
{"id": "PMID:13433", "title": "DNA viruses: cooperativity and regulation through conformational changes as features of phage assembly.", "content": "The assembly of bacteriophages provides experimental model systems for the study of regulation at the level of gene products. We discuss the hypothesis of regulation through sequentially induced conformational changes by which precursor-assemblies become ready at a specific stage of maturation to interact with an additional gene product or nucleic acids. Phage mutants provide excellent experimental model systems for studying, for example, the role and fate of the core in the prehead assembly. The conservative maturation of the prehead to the final, stable head consists of several steps whose complexity reflect that of the virus. It includes packaging of DNA. The surface lattice of maturing preheads apparently undergoes several steps characterized by different conformational states as suggested by in vitro studies on a morphological variant of the prehead, the polyhead of phage T4 (Steven, Couture, Aebi & Showe 1976; Laemmli, Amos & Klug 1976). Addition of a partly purified, enriched proteolytic fraction--which is gene 21-dependent--to empty purified polyheads leads to different conformational states. These seem to go in a direction approaching the structure of the surface of finished capsids as studied by Aebi et al. on gene 24 related (Bijlenga, Aebi & Kellenberger 1976) and other genetically defined giant-variants of T4 phage (Doermann, Eiserling & Boehner 1973). We show some experiments which suggest that high cooperativity is responsible for the stabilization of capsids. The activation energy necessary for dissociation of capsids is very high, 247 kJ for T4 capsids, and 10% smaller for T2. Once the energy barrier has been overcome, the capsids are first structurally modified before they undergo partial and finally complete dissociation.", "contents": "DNA viruses: cooperativity and regulation through conformational changes as features of phage assembly. The assembly of bacteriophages provides experimental model systems for the study of regulation at the level of gene products. We discuss the hypothesis of regulation through sequentially induced conformational changes by which precursor-assemblies become ready at a specific stage of maturation to interact with an additional gene product or nucleic acids. Phage mutants provide excellent experimental model systems for studying, for example, the role and fate of the core in the prehead assembly. The conservative maturation of the prehead to the final, stable head consists of several steps whose complexity reflect that of the virus. It includes packaging of DNA. The surface lattice of maturing preheads apparently undergoes several steps characterized by different conformational states as suggested by in vitro studies on a morphological variant of the prehead, the polyhead of phage T4 (Steven, Couture, Aebi & Showe 1976; Laemmli, Amos & Klug 1976). Addition of a partly purified, enriched proteolytic fraction--which is gene 21-dependent--to empty purified polyheads leads to different conformational states. These seem to go in a direction approaching the structure of the surface of finished capsids as studied by Aebi et al. on gene 24 related (Bijlenga, Aebi & Kellenberger 1976) and other genetically defined giant-variants of T4 phage (Doermann, Eiserling & Boehner 1973). We show some experiments which suggest that high cooperativity is responsible for the stabilization of capsids. The activation energy necessary for dissociation of capsids is very high, 247 kJ for T4 capsids, and 10% smaller for T2. Once the energy barrier has been overcome, the capsids are first structurally modified before they undergo partial and finally complete dissociation."}
{"id": "PMID:13434", "title": "Structure and assembly of the capsid of bacteriophage P22.", "content": "Identification of the genes and proteins involved in phage P22 formation has permitted a detailed analysis of particle assembly, revealing some unexpected aspects. The polymerization of the major coat protein (gene 5 product) into an organized capsid is directed by a scaffolding protein (gene 8 product) which is absent from mature phage. The resulting capsid structure (prohead) is the precursor for DNA encapsidation. All of the scaffolding protein exits from the prohead in association with DNA packaging. These molecules then recycle, directing further rounds of prohead assembly. The structure of the prohead has been studied by electron microscopy of thin sections of phage infected cells, and by low angle X-ray scattering of concentrated particles. The results show that the prohead is a double shell structure, or a ball within a shell. The inner ball or shell is composed of the scaffolding protein while the outer shell is composed of coat protein. The conversion from prohead to mature capsid is associated with an expansion of the coat protein shell. It is possible that the scaffolding protein molecules exit through the capsid lattice. When DNA encapsidation within infected cells is blocked by mutation, scaffolding protein is trapped in proheads and cannot recycle. Under these conditions, the rate of synthesis of gp8 increases, so that normal proheads continue to form. These results suggest that free scaffolding protein negatively regulates its own further synthesis, providing a coupling between protein synthesis and protein assembly.", "contents": "Structure and assembly of the capsid of bacteriophage P22. Identification of the genes and proteins involved in phage P22 formation has permitted a detailed analysis of particle assembly, revealing some unexpected aspects. The polymerization of the major coat protein (gene 5 product) into an organized capsid is directed by a scaffolding protein (gene 8 product) which is absent from mature phage. The resulting capsid structure (prohead) is the precursor for DNA encapsidation. All of the scaffolding protein exits from the prohead in association with DNA packaging. These molecules then recycle, directing further rounds of prohead assembly. The structure of the prohead has been studied by electron microscopy of thin sections of phage infected cells, and by low angle X-ray scattering of concentrated particles. The results show that the prohead is a double shell structure, or a ball within a shell. The inner ball or shell is composed of the scaffolding protein while the outer shell is composed of coat protein. The conversion from prohead to mature capsid is associated with an expansion of the coat protein shell. It is possible that the scaffolding protein molecules exit through the capsid lattice. When DNA encapsidation within infected cells is blocked by mutation, scaffolding protein is trapped in proheads and cannot recycle. Under these conditions, the rate of synthesis of gp8 increases, so that normal proheads continue to form. These results suggest that free scaffolding protein negatively regulates its own further synthesis, providing a coupling between protein synthesis and protein assembly."}
{"id": "PMID:13435", "title": "Capsid transformation during packaging of bacteriophage lambdaDNA.", "content": "Assembly pathways of complex viruses might not be simple additions of one protein after another with rigid tertiary structure. It might in fact involve shifts in subunit structure, movement of subunits relative to each other to form new arrangements, transient action of proteins and protein segments, involvement of structure forming 'microenvironments' of the host. Thus morphogenesis of the bacteriophage lambda head starts with the formation of a core-containing DNA-free petit lambda particle. In a first transition, and dependent on a host function, the core is released, minor protein components of the capsid are processed and the particle's structure is altered, as shown by a change of its hydrodynamic properties. The resulting 'prehead' undergoes a second transition triggered by a complex of DNA and recognition protein (A-protein). This transition is more drastic than the first one. The particle doubles its volume without increasing in protein mass, the shell becomes thinner, and the surface structure is changed. Concomitantly with this process, the DNA becomes packaged and the particle becomes able to bind the small 'D-protein' in amounts equimolar to the capsid protein, which it could not do before. The D-protein addition probably causes another shift of the capsid structure. DNA packaging is completed, and the DNA is cut from concatemeric precursors to unit length molecules. Binding sites are created for the tail connector molecules which in turn allow the independently assembled tail to attach. Research on these processes proceeds along several lines: comparison of physical and chemical properties of particles accumulating in mutants; pulse-chase experiments on assembly precursors; morphogenesis in vitro; and model transitions of aberrant lambda polyheads.", "contents": "Capsid transformation during packaging of bacteriophage lambdaDNA. Assembly pathways of complex viruses might not be simple additions of one protein after another with rigid tertiary structure. It might in fact involve shifts in subunit structure, movement of subunits relative to each other to form new arrangements, transient action of proteins and protein segments, involvement of structure forming 'microenvironments' of the host. Thus morphogenesis of the bacteriophage lambda head starts with the formation of a core-containing DNA-free petit lambda particle. In a first transition, and dependent on a host function, the core is released, minor protein components of the capsid are processed and the particle's structure is altered, as shown by a change of its hydrodynamic properties. The resulting 'prehead' undergoes a second transition triggered by a complex of DNA and recognition protein (A-protein). This transition is more drastic than the first one. The particle doubles its volume without increasing in protein mass, the shell becomes thinner, and the surface structure is changed. Concomitantly with this process, the DNA becomes packaged and the particle becomes able to bind the small 'D-protein' in amounts equimolar to the capsid protein, which it could not do before. The D-protein addition probably causes another shift of the capsid structure. DNA packaging is completed, and the DNA is cut from concatemeric precursors to unit length molecules. Binding sites are created for the tail connector molecules which in turn allow the independently assembled tail to attach. Research on these processes proceeds along several lines: comparison of physical and chemical properties of particles accumulating in mutants; pulse-chase experiments on assembly precursors; morphogenesis in vitro; and model transitions of aberrant lambda polyheads."}
{"id": "PMID:13436", "title": "Structure and assembly of lipid-containing viruses, with special reference to bacteriophage PM2 as one type of model system.", "content": "The simpler lipid-containing viruses (influenza, Semliki Forest, PM2) may have a phospholipid bilayer sandwiched between an outer shell of protein and an internal nucleocapsid possessing helical or icosahedral symmetry. Extensive physical and chemical studies have enabled us to form a more detailed picture of the structure of bacteriophage PM2 and controlled stepwise degradation of the virion has helped us to localize the four viral proteins. The surface protein (II) of PM2 is basic and interacts with the acidic phosphatidylglycerol of the bilayer to stabilize the membrane. The nucleocapsid protein (III) has proteolipid characteristics and may interact with the phospholipids in a hydrophobic fashion. The spikes are formed from protein I and the fourth protein (IV) is closely associated with the DNA. It is possible to reassemble the virus by reversing the degradation steps. Assembly has been especially useful in revealing the processes whereby the proteins and lipids interact to form the bilayer. Furthermore, results of in vivo studies of phospholipid synthesis and both in vivo and in vitro studies of viral protein synthesis have enabled us to form a reasonably complete picture of the biosynthesis of PM2.", "contents": "Structure and assembly of lipid-containing viruses, with special reference to bacteriophage PM2 as one type of model system. The simpler lipid-containing viruses (influenza, Semliki Forest, PM2) may have a phospholipid bilayer sandwiched between an outer shell of protein and an internal nucleocapsid possessing helical or icosahedral symmetry. Extensive physical and chemical studies have enabled us to form a more detailed picture of the structure of bacteriophage PM2 and controlled stepwise degradation of the virion has helped us to localize the four viral proteins. The surface protein (II) of PM2 is basic and interacts with the acidic phosphatidylglycerol of the bilayer to stabilize the membrane. The nucleocapsid protein (III) has proteolipid characteristics and may interact with the phospholipids in a hydrophobic fashion. The spikes are formed from protein I and the fourth protein (IV) is closely associated with the DNA. It is possible to reassemble the virus by reversing the degradation steps. Assembly has been especially useful in revealing the processes whereby the proteins and lipids interact to form the bilayer. Furthermore, results of in vivo studies of phospholipid synthesis and both in vivo and in vitro studies of viral protein synthesis have enabled us to form a reasonably complete picture of the biosynthesis of PM2."}
{"id": "PMID:13437", "title": "Structure and assembly of filamentous bacterial viruses.", "content": "Filamentous bacterial viruses are flexible nucleoprotein rods, about 6 nm in diameter by 1000-2000 nm in length (depending on the virus strain). A protein shell encloses a central core of single-stranded circular DNA. The coat protein subunits forming the shell are largely alpha-helix, elongated in an axial direction, and also sloping radially, so as to overlap each other and give an arrangement of subunits reminiscent of scales on a fish. This arrangement of alpha-helices is rather like some models of myosin filaments. An early step in assembly of the virion is the formation of a complex between the viral DNA and an intracellular packaging protein that is not found in completed virions. Newly synthesized coat protein becomes associated with the plasma membrane of the cell. During the final steps of assembly, the packaging protein is displaced from the DNA and replaced by coat protein as the virion passes out through the plasma membrane of the host cell.", "contents": "Structure and assembly of filamentous bacterial viruses. Filamentous bacterial viruses are flexible nucleoprotein rods, about 6 nm in diameter by 1000-2000 nm in length (depending on the virus strain). A protein shell encloses a central core of single-stranded circular DNA. The coat protein subunits forming the shell are largely alpha-helix, elongated in an axial direction, and also sloping radially, so as to overlap each other and give an arrangement of subunits reminiscent of scales on a fish. This arrangement of alpha-helices is rather like some models of myosin filaments. An early step in assembly of the virion is the formation of a complex between the viral DNA and an intracellular packaging protein that is not found in completed virions. Newly synthesized coat protein becomes associated with the plasma membrane of the cell. During the final steps of assembly, the packaging protein is displaced from the DNA and replaced by coat protein as the virion passes out through the plasma membrane of the host cell."}
{"id": "PMID:13438", "title": "RNA viruses: stabilization of brome mosaic virus.", "content": "The relative importances of protein-protein and RNA-protein interactions in stabilizing the architecture of brome mosaic virus particles are discussed in the light of the following experimental evidence: (a) disassembly pathways of the virus particles, (b) reassembly of the virus and self-association capacity of the protein moiety, and (c) the role of divalent cations in virus stabilization, and their relevance to localization of the RNA in the virus particles. Evidence is given that the capsid of BMV is primarily stabilized by hydrophobic bonds at low pH, but not around and above neutrality where RNA-protein electrostatic interactions are essential to the integrity of the virus particles. A model is proposed for the structure of BMV in the different configurational states.", "contents": "RNA viruses: stabilization of brome mosaic virus. The relative importances of protein-protein and RNA-protein interactions in stabilizing the architecture of brome mosaic virus particles are discussed in the light of the following experimental evidence: (a) disassembly pathways of the virus particles, (b) reassembly of the virus and self-association capacity of the protein moiety, and (c) the role of divalent cations in virus stabilization, and their relevance to localization of the RNA in the virus particles. Evidence is given that the capsid of BMV is primarily stabilized by hydrophobic bonds at low pH, but not around and above neutrality where RNA-protein electrostatic interactions are essential to the integrity of the virus particles. A model is proposed for the structure of BMV in the different configurational states."}
{"id": "PMID:13439", "title": "Fluorescent probe studies of haptoglobin type 2-1.", "content": "Haptoglobin is an alpha2 serum protein that forms an irreversible complex with hemoglobin. The combination between these two macromolecules resembles the binding of an antigen to its antibody except that the complex remains soluble. This investigation was undertaken to determine the nature of the hydrophobic sites on haptoglobin type 2-1. The interaction of 1-anilinonphthalene-8-sulfonate (ANS) with haptoglobin type 2-1 is characterized by a flourescence intensity in solutions containing ANS and haptoglobin as the pH is decreased from 9 to 4. The dissociation constant for the ANS interaction with haptoglobin 2-1 is 5.8 x 10--5 M at pH 7.0, 5.2 X 10--5 M at pH 5.0 AND 30.3 X 10--5 M at pH 4.0. Fmax shows no change in the pH range 6-9 but does show an increase at pH 4.0 when compared to the neutral region.", "contents": "Fluorescent probe studies of haptoglobin type 2-1. Haptoglobin is an alpha2 serum protein that forms an irreversible complex with hemoglobin. The combination between these two macromolecules resembles the binding of an antigen to its antibody except that the complex remains soluble. This investigation was undertaken to determine the nature of the hydrophobic sites on haptoglobin type 2-1. The interaction of 1-anilinonphthalene-8-sulfonate (ANS) with haptoglobin type 2-1 is characterized by a flourescence intensity in solutions containing ANS and haptoglobin as the pH is decreased from 9 to 4. The dissociation constant for the ANS interaction with haptoglobin 2-1 is 5.8 x 10--5 M at pH 7.0, 5.2 X 10--5 M at pH 5.0 AND 30.3 X 10--5 M at pH 4.0. Fmax shows no change in the pH range 6-9 but does show an increase at pH 4.0 when compared to the neutral region."}
{"id": "PMID:13440", "title": "Models for biological ion exchangers. I. Proton magnetic resonance studies of water structure in Bio-Rex 70.", "content": "Bio-Rex 70, a carboxylic acid cation exchanger, is studied as a biological ion-exchanger resin model for cellular cytoplasm. High-resolution proton magnetic resonance spectra of 1l ionic forms of Bio-Rex 70 are determined. From measured cation exchange capacities, water contents, and chemical shifts for the resin-phase water protons, the dependence of the chemical shift on the counter ion is calculated. The observed chemical shifts (Hz/geq/kg internal water, referred to the Ba2+ form) for each ionic form are: H+, --0.5; Li+, --0.2; Na+, 1.2; K+, 2; Rb+, 2.1; Ag+, --0.4; NH4+, --2.0; NMe4+, 1.2; NEt4+, 1.8; Mg2+, --2.0; Ca2+, --1.5; Sr2+, --0.6; Ba2+, 0.0 Zn2+, --2.3; Cd2+, --4.7; and La3+, --3.3. The results are in good agreement with earlier studies on Dowex 50, indicating that the carboxylate ion exchanger behaves like a concentrated polyelectrolyte. The widths at half-height for the internal water peaks of the polyvalent forms are quite large, ranging from 40 to 100 Hz.", "contents": "Models for biological ion exchangers. I. Proton magnetic resonance studies of water structure in Bio-Rex 70. Bio-Rex 70, a carboxylic acid cation exchanger, is studied as a biological ion-exchanger resin model for cellular cytoplasm. High-resolution proton magnetic resonance spectra of 1l ionic forms of Bio-Rex 70 are determined. From measured cation exchange capacities, water contents, and chemical shifts for the resin-phase water protons, the dependence of the chemical shift on the counter ion is calculated. The observed chemical shifts (Hz/geq/kg internal water, referred to the Ba2+ form) for each ionic form are: H+, --0.5; Li+, --0.2; Na+, 1.2; K+, 2; Rb+, 2.1; Ag+, --0.4; NH4+, --2.0; NMe4+, 1.2; NEt4+, 1.8; Mg2+, --2.0; Ca2+, --1.5; Sr2+, --0.6; Ba2+, 0.0 Zn2+, --2.3; Cd2+, --4.7; and La3+, --3.3. The results are in good agreement with earlier studies on Dowex 50, indicating that the carboxylate ion exchanger behaves like a concentrated polyelectrolyte. The widths at half-height for the internal water peaks of the polyvalent forms are quite large, ranging from 40 to 100 Hz."}
{"id": "PMID:13444", "title": "[Effects of antianxiety drugs on the water intake in trained and untrained rats and mice (author's transl)].", "content": "In water-deprived rats and mice, animals trained to the test situation spent more time in drinking than naive animals (first exposure to the test situation). The time spent in drinking, either during 5 min or during 10 min was recorded. As compared to controls, benzodiazepines, phenobarbital, meprobamate, and mecloqualone increased drinking time whether the experiments were run on naive or on experienced animals [5 or 10 (in mice) and 9 (in rats) exposures in the test situation]. All drugs were injected i.p. 30 min before testing. This release of the drinking behavior was more pronounced during the last 5 min than during the first 5 min of the 10 min test session. These results suggest that: 1. The inhibition of water intake of naive animals as compared to trained rats and mice, could be related to some emotional factors elicited by the first exposure to an unknown situation. 2. The increase in drinking time induced by the antianxiety drugs in a novel and in a familiar situation seems difficult to correlate only with the antianxiety action of these compounds. 3. Antianxiety drugs could interfere with the regulatory mechanism of thirst.", "contents": "[Effects of antianxiety drugs on the water intake in trained and untrained rats and mice (author's transl)]. In water-deprived rats and mice, animals trained to the test situation spent more time in drinking than naive animals (first exposure to the test situation). The time spent in drinking, either during 5 min or during 10 min was recorded. As compared to controls, benzodiazepines, phenobarbital, meprobamate, and mecloqualone increased drinking time whether the experiments were run on naive or on experienced animals [5 or 10 (in mice) and 9 (in rats) exposures in the test situation]. All drugs were injected i.p. 30 min before testing. This release of the drinking behavior was more pronounced during the last 5 min than during the first 5 min of the 10 min test session. These results suggest that: 1. The inhibition of water intake of naive animals as compared to trained rats and mice, could be related to some emotional factors elicited by the first exposure to an unknown situation. 2. The increase in drinking time induced by the antianxiety drugs in a novel and in a familiar situation seems difficult to correlate only with the antianxiety action of these compounds. 3. Antianxiety drugs could interfere with the regulatory mechanism of thirst."}
{"id": "PMID:13445", "title": "Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment.", "content": "Newborn rats were treated at 1 and 2 days after birth with 100 mg/kg 6-hydroxydopamine (60HDA), s.c. Testing on several operant behavioural tasks was begun at 6 months of age. On a fixed ratio 30 (FR 30) schedule of food reinforcement, the neonatal 60HDA treated rats responded at a significantly higher rate. Further analysis of the FR 30 response pattern indicated that the higher rate was due to a decrease in the amount of time spent pausing after the receipt of each reinforcer. The 60HDA treatment failed to alter the rat's behaviour during the extinction of the FR 30 response and on the progressive ratio or variable interval schedules of food reinforcement. Biochemical analysis of several brain areas at 9 months of age showed a decrease in noradrenaline (NA) levels in the cerebral cortex and hippocampus, while in the pons-medulla NA content was doubled. The tyrosine hydroxylase activity in these same brain areas was not significantly altered, but there appeared to be some decrease in the activity of this enzyme in the hippocampus. Comparison of the operant behavioural effects seen after various lesioning procedures in this and other studies, suggest the effects on FR performance are a result of destruction of NA neurons in the hippocampus and/or the apparent regeneration of neurons in the pons-medulla.", "contents": "Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment. Newborn rats were treated at 1 and 2 days after birth with 100 mg/kg 6-hydroxydopamine (60HDA), s.c. Testing on several operant behavioural tasks was begun at 6 months of age. On a fixed ratio 30 (FR 30) schedule of food reinforcement, the neonatal 60HDA treated rats responded at a significantly higher rate. Further analysis of the FR 30 response pattern indicated that the higher rate was due to a decrease in the amount of time spent pausing after the receipt of each reinforcer. The 60HDA treatment failed to alter the rat's behaviour during the extinction of the FR 30 response and on the progressive ratio or variable interval schedules of food reinforcement. Biochemical analysis of several brain areas at 9 months of age showed a decrease in noradrenaline (NA) levels in the cerebral cortex and hippocampus, while in the pons-medulla NA content was doubled. The tyrosine hydroxylase activity in these same brain areas was not significantly altered, but there appeared to be some decrease in the activity of this enzyme in the hippocampus. Comparison of the operant behavioural effects seen after various lesioning procedures in this and other studies, suggest the effects on FR performance are a result of destruction of NA neurons in the hippocampus and/or the apparent regeneration of neurons in the pons-medulla."}
{"id": "PMID:13446", "title": "Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects.", "content": "The effects of haloperidol, alone and in combination with atropine, were compared with the effects of clozapine, alone and in combination with physostigmine, in a variety of tests commonly used to characterize neuroleptic compounds. It was found that clozapine in combination with physostigmine did not present the profile of activity of a classical neuroleptic agent; neither did haloperidol in combination with atropine present that of clozapine. In fact, some effects of haloperidol (catalepsy) were antagonized by atropine, while others (induction of striatal DA-receptor hypersensitivity) were enhanced. It is concluded that the interaction between dopaminergic and cholinergic systems in the striatum is highly complex, and that a neuroleptic possessing both potent DA-receptor blocking and muscarinic anticholinergic activity, while being less likely to cause parkinsonism in patients, would be more likely to induce tardive dyskinesias.", "contents": "Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects. The effects of haloperidol, alone and in combination with atropine, were compared with the effects of clozapine, alone and in combination with physostigmine, in a variety of tests commonly used to characterize neuroleptic compounds. It was found that clozapine in combination with physostigmine did not present the profile of activity of a classical neuroleptic agent; neither did haloperidol in combination with atropine present that of clozapine. In fact, some effects of haloperidol (catalepsy) were antagonized by atropine, while others (induction of striatal DA-receptor hypersensitivity) were enhanced. It is concluded that the interaction between dopaminergic and cholinergic systems in the striatum is highly complex, and that a neuroleptic possessing both potent DA-receptor blocking and muscarinic anticholinergic activity, while being less likely to cause parkinsonism in patients, would be more likely to induce tardive dyskinesias."}
{"id": "PMID:13447", "title": "Alterations of mouse adrenal medullary catecholamines and enzymes in response to attack: effect of pre- and post-treatment with phenobarbital.", "content": "Group-housed male C57BR/cdJ mice (victims) were exposed to attack for 10 min daily for up to 14 days by male Swiss-Webster mice, made aggressive by prolonged isolation. Their adrenal glands were analyzed for tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities and for norepinephrine (NE) and epinephrine (EPI) concentrations. TH was increased to 41 per cent above control after two exposures and remained elevated through 14 exposures to attack. PNMT was increased to 29 per cent above control after 2 days and increased further to 50 per cent above control after 14 days of attack. Both NE and EPI increased to 88 per cent and 51 per cent above control, respectively, after 7 days. In victim mice recuperating after 1 week of daily stress, EPI levels and PNMT activities were back to normal after 4 days whereas NE levels and TH activities returned to normal only after 1 week. Phenobarbital (40 mg/kg, i.m.) was effective in preventing the biochemical changes when given 2 h prior to each daily attack but was ineffective when given immediately after each daily stress.", "contents": "Alterations of mouse adrenal medullary catecholamines and enzymes in response to attack: effect of pre- and post-treatment with phenobarbital. Group-housed male C57BR/cdJ mice (victims) were exposed to attack for 10 min daily for up to 14 days by male Swiss-Webster mice, made aggressive by prolonged isolation. Their adrenal glands were analyzed for tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities and for norepinephrine (NE) and epinephrine (EPI) concentrations. TH was increased to 41 per cent above control after two exposures and remained elevated through 14 exposures to attack. PNMT was increased to 29 per cent above control after 2 days and increased further to 50 per cent above control after 14 days of attack. Both NE and EPI increased to 88 per cent and 51 per cent above control, respectively, after 7 days. In victim mice recuperating after 1 week of daily stress, EPI levels and PNMT activities were back to normal after 4 days whereas NE levels and TH activities returned to normal only after 1 week. Phenobarbital (40 mg/kg, i.m.) was effective in preventing the biochemical changes when given 2 h prior to each daily attack but was ineffective when given immediately after each daily stress."}
{"id": "PMID:13448", "title": "Cyclic GMP in the CSF of patients with schizophrenia before and after neuroleptic treatment.", "content": "Cerebrospinal fluid (CSF) cyclic GMP may derive from central cholinergic neurotransmission. Measurement of CSF cyclic GMP may allow evaluation of possible implications of the dopaminergic hyperactivity in schizophrenia proposed by the dopamine hypothesis. The CSF cyclic GMP levels in 27 drug-free schizophrenic patients was measured and compared to that in 9 psychiatrically-healthy individuals. The mean CSF cyclic GMP level of the schizophrenic patients was 23 per cent lower than that of the control group, but this difference did not attain statistical significance. In addition the CSF cyclic GMP levels in a group of 10 schizophrenic patients were compared before and after 2 months of neuroleptic treatment. The mean level of cyclic GMP rose 50 per cent after treatment with phenothiazines (P less than 0.05). These results could indicate some tendency for decreased activity of central cholinergic neurons in schizophrenia as well as a restored dopaminergic-cholinergic balance after neuroleptic treatment.", "contents": "Cyclic GMP in the CSF of patients with schizophrenia before and after neuroleptic treatment. Cerebrospinal fluid (CSF) cyclic GMP may derive from central cholinergic neurotransmission. Measurement of CSF cyclic GMP may allow evaluation of possible implications of the dopaminergic hyperactivity in schizophrenia proposed by the dopamine hypothesis. The CSF cyclic GMP levels in 27 drug-free schizophrenic patients was measured and compared to that in 9 psychiatrically-healthy individuals. The mean CSF cyclic GMP level of the schizophrenic patients was 23 per cent lower than that of the control group, but this difference did not attain statistical significance. In addition the CSF cyclic GMP levels in a group of 10 schizophrenic patients were compared before and after 2 months of neuroleptic treatment. The mean level of cyclic GMP rose 50 per cent after treatment with phenothiazines (P less than 0.05). These results could indicate some tendency for decreased activity of central cholinergic neurons in schizophrenia as well as a restored dopaminergic-cholinergic balance after neuroleptic treatment."}
{"id": "PMID:13470", "title": "Pulmonary function in premature lambs during the first few hours of life.", "content": "This study establishes the mean values, variations, and trend of pulmonary function during the first few hours of life in premature lambs. Measurements of intraesophaheal and tracheal pressure, air flow, tidal volume, and functional residual capacity enabled calculations of lung compliance, specific lung compliance, and inspiratory and expiratory resistance of the lungs. Arterial carbon dioxide tension and pH were maintained within a physiologic range. Mean arterial oxygen tension (PO2) at elevated inspired oxygen tension, varied in the individual animals from 51 to 185 mm Hg at an inspired oxygen concentration of 46 to 71%. It was found that the lungs of premature lambs delivered by cesarean section were mechanically unstable; the lambs were all ineffectual at breathing and required some form of mechanical ventilation. During the first 6 hours of postnatal life the lungs of premature lambs are characterized by a wide range of mechanical values and blood gas tensions.", "contents": "Pulmonary function in premature lambs during the first few hours of life. This study establishes the mean values, variations, and trend of pulmonary function during the first few hours of life in premature lambs. Measurements of intraesophaheal and tracheal pressure, air flow, tidal volume, and functional residual capacity enabled calculations of lung compliance, specific lung compliance, and inspiratory and expiratory resistance of the lungs. Arterial carbon dioxide tension and pH were maintained within a physiologic range. Mean arterial oxygen tension (PO2) at elevated inspired oxygen tension, varied in the individual animals from 51 to 185 mm Hg at an inspired oxygen concentration of 46 to 71%. It was found that the lungs of premature lambs delivered by cesarean section were mechanically unstable; the lambs were all ineffectual at breathing and required some form of mechanical ventilation. During the first 6 hours of postnatal life the lungs of premature lambs are characterized by a wide range of mechanical values and blood gas tensions."}
{"id": "PMID:13472", "title": "Calculations for pH during CO2 and O2 exchange with blood.", "content": "New mathematical formulas are presented to calculate directly the change in blood pH during CO2, and O2 exchange with blood. pH changes are calculated from changes in blood PCO2 and saturation values or from changes in blood PCO2 and blood PO2 values. Computational results agree well with information obtained from a Dill nomogram. These new formulas have applicability to the modelling of gas exchange in blood oxygenators as well as to estimating blood acid-base parameters following the mixing of blood samples.", "contents": "Calculations for pH during CO2 and O2 exchange with blood. New mathematical formulas are presented to calculate directly the change in blood pH during CO2, and O2 exchange with blood. pH changes are calculated from changes in blood PCO2 and saturation values or from changes in blood PCO2 and blood PO2 values. Computational results agree well with information obtained from a Dill nomogram. These new formulas have applicability to the modelling of gas exchange in blood oxygenators as well as to estimating blood acid-base parameters following the mixing of blood samples."}
{"id": "PMID:13477", "title": "[Biochemistry of collagen and the locomoter apparatus (Hereditary connective tissue diseases and rheumatic diseases. Part I].", "content": "The elementary collagen molecule consists of three chains rolled into a spiral and ending in nonhelical telopeptides. In cutaneous collagen, there are two types of chains, in cartilaginous collagen there is only one. In the synthesis, several enzymes play successive parts: proline hydroxylase, lysine hydroxylase, then pro-collagen peptidase and finally, lysine oxidase and hydroxylysine oxidase; their coordinated actions ultimately allow the chains to establish the transverse intra and intermolecular links which give the collagen fiber its cohesion. The type and number of these transverse links vary from one tissue to another. Specific collagenases make collagen degradation possible.", "contents": "[Biochemistry of collagen and the locomoter apparatus (Hereditary connective tissue diseases and rheumatic diseases. Part I]. The elementary collagen molecule consists of three chains rolled into a spiral and ending in nonhelical telopeptides. In cutaneous collagen, there are two types of chains, in cartilaginous collagen there is only one. In the synthesis, several enzymes play successive parts: proline hydroxylase, lysine hydroxylase, then pro-collagen peptidase and finally, lysine oxidase and hydroxylysine oxidase; their coordinated actions ultimately allow the chains to establish the transverse intra and intermolecular links which give the collagen fiber its cohesion. The type and number of these transverse links vary from one tissue to another. Specific collagenases make collagen degradation possible."}
{"id": "PMID:13478", "title": "The van Slyke equation.", "content": "The Henderson-Hasselbalch equation has always occupied a central place in the description of the acid-base status of the blood. An equation of similar importance is the equation for the CO2 equilibration curve of blood in vitro. It is proposed to name this the Van Slyke equation: a - 24.4 = - (2.3 X b + 7.7) X (c - 7.40) + d/(1 - 0.023 X b), where a = bicarbonate concentration in plasma/(mmol/l), b = hemoglobin concentration in blood/(mmol/l), c = pH of plasma at 37 degrees C, d = base excess concentration in blood/(mmol/l). These two equations provide an arithmetic algorithm for calculation of the various acid-base variables of the blood after measuring the pH, the pCO2, and the hemoglobin concentration.", "contents": "The van Slyke equation. The Henderson-Hasselbalch equation has always occupied a central place in the description of the acid-base status of the blood. An equation of similar importance is the equation for the CO2 equilibration curve of blood in vitro. It is proposed to name this the Van Slyke equation: a - 24.4 = - (2.3 X b + 7.7) X (c - 7.40) + d/(1 - 0.023 X b), where a = bicarbonate concentration in plasma/(mmol/l), b = hemoglobin concentration in blood/(mmol/l), c = pH of plasma at 37 degrees C, d = base excess concentration in blood/(mmol/l). These two equations provide an arithmetic algorithm for calculation of the various acid-base variables of the blood after measuring the pH, the pCO2, and the hemoglobin concentration."}
{"id": "PMID:13479", "title": "Physiological viewpoints on clinical acid-base diagnostics.", "content": "Acid-base physiology is concerned with sources, extent, and control of hydrogen ion donation in the body, at the organ-physiological as well as the molecular level of study. With the introduction of Van Slyke's methods for quantitative carbon dioxide measurements in biological fluids, one important source of hydrogen ion donation became identifiable; and these and derived methods have permitted of fairly precise quantitative descriptions of transport and pulmonary elimination of carbon dioxide. However, the inevitable operational concept of non-carbonic (non-volatile) contributions to the titratable acidity of the body fluids has been a cause of considerable methodological and conceptual difficulties; and whereas it is now possible by means of the micro-equilibration technique to make accurate assessments of the concentration of non-volatile titratable acid (base) in blood, the question of the physiological relevance of the concept of 'base excess' remains open. In particular, the concept of non-carbonic acid does not possess a specific relevance with respect to the acid-base physiology of kidney, bone, and gastro-intestinal tract comparable to the 'substrate-specificity of carbon dioxide with respect to the lung. Our studies indicate that a subdivision of the titratable non-carbonic acid of any biological medium in two subcomponents will provide an improvement of specificity, adequate for a system physiological approach at the organ level. Thus, a distinction should be made between (1) processes of hydrogen ion donation, reversible by endogenous metabolic means (quantitated in terms of the component MA = metabolizable non-carbonic acid) and (2) processes of hydrogen ion donation associated with gastro-intestinal, skeletal, and renal transport, storage, and control of non-metabolizable non-carbonic acid (NA). Some implications of this distinction for acid-base physiology and acid-base diagnostics are discussed.", "contents": "Physiological viewpoints on clinical acid-base diagnostics. Acid-base physiology is concerned with sources, extent, and control of hydrogen ion donation in the body, at the organ-physiological as well as the molecular level of study. With the introduction of Van Slyke's methods for quantitative carbon dioxide measurements in biological fluids, one important source of hydrogen ion donation became identifiable; and these and derived methods have permitted of fairly precise quantitative descriptions of transport and pulmonary elimination of carbon dioxide. However, the inevitable operational concept of non-carbonic (non-volatile) contributions to the titratable acidity of the body fluids has been a cause of considerable methodological and conceptual difficulties; and whereas it is now possible by means of the micro-equilibration technique to make accurate assessments of the concentration of non-volatile titratable acid (base) in blood, the question of the physiological relevance of the concept of 'base excess' remains open. In particular, the concept of non-carbonic acid does not possess a specific relevance with respect to the acid-base physiology of kidney, bone, and gastro-intestinal tract comparable to the 'substrate-specificity of carbon dioxide with respect to the lung. Our studies indicate that a subdivision of the titratable non-carbonic acid of any biological medium in two subcomponents will provide an improvement of specificity, adequate for a system physiological approach at the organ level. Thus, a distinction should be made between (1) processes of hydrogen ion donation, reversible by endogenous metabolic means (quantitated in terms of the component MA = metabolizable non-carbonic acid) and (2) processes of hydrogen ion donation associated with gastro-intestinal, skeletal, and renal transport, storage, and control of non-metabolizable non-carbonic acid (NA). Some implications of this distinction for acid-base physiology and acid-base diagnostics are discussed."}
{"id": "PMID:13480", "title": "Stoichiometric concentration and chemical potential.", "content": "It has been recommended to use SI units in clinical chemistry. A consequence of this is that pH is reported as the excess chemical potential (or standard chemical potential) of hydrogen ions with the unit kJ/mol. On the basis of the excess chemical potential of H+ it is possible to calculate the hydrogen ion concentration in the system = the equilibrium concentration of H+ = the concentration of free H+. This quantity must be clearly distinguished from the stoichiometric concentration of H+ = the excess concentration of total H+, which indicates the amount of added or removed H+. The latter quantity with opposite sign has been called the excess concentration of base, but the designation \"stoichiometric concentration of H+\" seems to be more logical. The general principles for description of a component in a chemical system are based on (1) an extensive quantity (the stoichiometric amount of substance), and (2) an intensive quantity (the excess chemical potential); the product of these has the dimension of energy.", "contents": "Stoichiometric concentration and chemical potential. It has been recommended to use SI units in clinical chemistry. A consequence of this is that pH is reported as the excess chemical potential (or standard chemical potential) of hydrogen ions with the unit kJ/mol. On the basis of the excess chemical potential of H+ it is possible to calculate the hydrogen ion concentration in the system = the equilibrium concentration of H+ = the concentration of free H+. This quantity must be clearly distinguished from the stoichiometric concentration of H+ = the excess concentration of total H+, which indicates the amount of added or removed H+. The latter quantity with opposite sign has been called the excess concentration of base, but the designation \"stoichiometric concentration of H+\" seems to be more logical. The general principles for description of a component in a chemical system are based on (1) an extensive quantity (the stoichiometric amount of substance), and (2) an intensive quantity (the excess chemical potential); the product of these has the dimension of energy."}
{"id": "PMID:13481", "title": "Gastrin, antral g cells, and gastric acid in secretagogue-induced and antihistamine-inhibited duodenal ulcers.", "content": "In fasting control rats there was continuous basal gastric acid secretion, with a low plasma gastrin and antral G-cells full or immunofluroescent gastrin. After subcutaneous infusion of the gastric secretagogues, pentagastrin + carbachol, there was a six-hour period of gastric hypersecretion, but no change in plasma and G-cell gastrin. Pretreatment with the antihistamine derivative, Pfizer UK-9040, decreased both basal and stimulated acid secretion, whereas plasma gastrin levels increased and the antral G-cells were emptied of gastrin. These results suggest that this antihistamine derivative decreases gastric acid secretion by a direct action on the parietal cells and not by reducing gastrin release from the G-cells. The increased release of gastrin from the G-cells may be secondary to decreased gastric acid production, or more probably by a direct stimulation of the antral G-cells.", "contents": "Gastrin, antral g cells, and gastric acid in secretagogue-induced and antihistamine-inhibited duodenal ulcers. In fasting control rats there was continuous basal gastric acid secretion, with a low plasma gastrin and antral G-cells full or immunofluroescent gastrin. After subcutaneous infusion of the gastric secretagogues, pentagastrin + carbachol, there was a six-hour period of gastric hypersecretion, but no change in plasma and G-cell gastrin. Pretreatment with the antihistamine derivative, Pfizer UK-9040, decreased both basal and stimulated acid secretion, whereas plasma gastrin levels increased and the antral G-cells were emptied of gastrin. These results suggest that this antihistamine derivative decreases gastric acid secretion by a direct action on the parietal cells and not by reducing gastrin release from the G-cells. The increased release of gastrin from the G-cells may be secondary to decreased gastric acid production, or more probably by a direct stimulation of the antral G-cells."}
{"id": "PMID:13482", "title": "Effect of resection of antrum and duodenal bulb on sham-feeding-induced inhibition of canine gastric secretion.", "content": "In dogs with Heidenhain pouches and oesophageal and gastric fistulae, sham feeding inhibited pentagastrin-stimulated Heidenhain pouch acid output. Resection of the antrum and the duodenalbulb reduced oin stomach was diverted through the gastric cannula. The present results are conid secretion at least partly by inducing a vagal release of an inhibitory hormone. The results suggest that this hormone is released from the antrum and the duodenal bulb.", "contents": "Effect of resection of antrum and duodenal bulb on sham-feeding-induced inhibition of canine gastric secretion. In dogs with Heidenhain pouches and oesophageal and gastric fistulae, sham feeding inhibited pentagastrin-stimulated Heidenhain pouch acid output. Resection of the antrum and the duodenalbulb reduced oin stomach was diverted through the gastric cannula. The present results are conid secretion at least partly by inducing a vagal release of an inhibitory hormone. The results suggest that this hormone is released from the antrum and the duodenal bulb."}
{"id": "PMID:13488", "title": "[Exercise hemodynamics and renin before and after acute beta block in patients with essential hypertension].", "content": "Hemodynamic and renin studies at rest and during graded upright ergometry were performed in 21 patients with essential hypertension before and after propranolol. Beta-adrenergic receptor blockade reduced exercise-stimulated cardiac and renin responses significantly more when compared with the corresponding effects at rest. Propranolol increased peripheral resistance at rest but not during exercise. The degree of the individual hemodynamic changes after propranolol correlated better with the corresponding control values than with age or renin. A direct relationship between the percent reduction of heart rate and renin responses after acute beta-blockade indicates a parallel suppression of cardiac and renal receptor functions.", "contents": "[Exercise hemodynamics and renin before and after acute beta block in patients with essential hypertension]. Hemodynamic and renin studies at rest and during graded upright ergometry were performed in 21 patients with essential hypertension before and after propranolol. Beta-adrenergic receptor blockade reduced exercise-stimulated cardiac and renin responses significantly more when compared with the corresponding effects at rest. Propranolol increased peripheral resistance at rest but not during exercise. The degree of the individual hemodynamic changes after propranolol correlated better with the corresponding control values than with age or renin. A direct relationship between the percent reduction of heart rate and renin responses after acute beta-blockade indicates a parallel suppression of cardiac and renal receptor functions."}
{"id": "PMID:13489", "title": "[The burden of a general medical clinic with patients after suicide attempts].", "content": "All 125 patients who entered the \"suicide ward\" of the Medical Department of a large public hospital during 1974 were analyzed according to age and sex distribution, duration of hospital stay, motivation and method of committing suicide and fate after recovering from the acute phase of intoxication. Motivation to commit suicide was mainly due to conflicting interpersonal relations. Suicide attempts were 3 times more frequent in women than in men. 49% of all suicide attempts were considered to be of the \"cry for help\" variety and 29% were classified as obviously ineffective but serious attempts of self-killing. The remaining 22% of patients wanted to mark a \"caesura\" in their lives. Since the early phase of recovery is of utmost importance for the patient's future, medical and nursing staff have to be trained and experienced in coping with the suicide patient's numerous problems. The permanent collaboration of an experienced psychiatrist within the staff of larger acute-phase hospitals is highly desirable in order to analyze the underlying social and medical problems, assess the danger of a renewed suicide attempt, start early and appropriate therapy and train hospital staff and nurses.", "contents": "[The burden of a general medical clinic with patients after suicide attempts]. All 125 patients who entered the \"suicide ward\" of the Medical Department of a large public hospital during 1974 were analyzed according to age and sex distribution, duration of hospital stay, motivation and method of committing suicide and fate after recovering from the acute phase of intoxication. Motivation to commit suicide was mainly due to conflicting interpersonal relations. Suicide attempts were 3 times more frequent in women than in men. 49% of all suicide attempts were considered to be of the \"cry for help\" variety and 29% were classified as obviously ineffective but serious attempts of self-killing. The remaining 22% of patients wanted to mark a \"caesura\" in their lives. Since the early phase of recovery is of utmost importance for the patient's future, medical and nursing staff have to be trained and experienced in coping with the suicide patient's numerous problems. The permanent collaboration of an experienced psychiatrist within the staff of larger acute-phase hospitals is highly desirable in order to analyze the underlying social and medical problems, assess the danger of a renewed suicide attempt, start early and appropriate therapy and train hospital staff and nurses."}
{"id": "PMID:13491", "title": "[Drug-induced lung diseases].", "content": "Adverse drug reactions involving different organs, including the lung, are numerous; much more numerous, however, are the offending drugs. According to the results of the Boston Collaborative Drug Surveillance Program, adverse reactions occur in about 6% of all drug exposures and 28% of all patients. Drug-induced lung diseases may present as bronchial reactions (e.g. bronchial asthma), diseases of the parenchyma (e.g. pulmonary infiltrates with eosinophilia, diffuse fibrosing alveolitis), of the pulmonary vasculature (vasculitis) and of the pleura (e.g. pleurisy or pleural fibrosis). Pathogenetically the two most pertinent types of reaction are hypersensitivity or toxic reactions, and less often biologic reactions such as opportunistic infections after cytotoxic and immunosuppressive therapy. Many drug-induced respiratory diseases are reversible upon withdrawal of the offending agent; others may be irreversibly or even progress.", "contents": "[Drug-induced lung diseases]. Adverse drug reactions involving different organs, including the lung, are numerous; much more numerous, however, are the offending drugs. According to the results of the Boston Collaborative Drug Surveillance Program, adverse reactions occur in about 6% of all drug exposures and 28% of all patients. Drug-induced lung diseases may present as bronchial reactions (e.g. bronchial asthma), diseases of the parenchyma (e.g. pulmonary infiltrates with eosinophilia, diffuse fibrosing alveolitis), of the pulmonary vasculature (vasculitis) and of the pleura (e.g. pleurisy or pleural fibrosis). Pathogenetically the two most pertinent types of reaction are hypersensitivity or toxic reactions, and less often biologic reactions such as opportunistic infections after cytotoxic and immunosuppressive therapy. Many drug-induced respiratory diseases are reversible upon withdrawal of the offending agent; others may be irreversibly or even progress."}
{"id": "PMID:13495", "title": "Mode of action of beta blockers in angina pectoris.", "content": "The therapeutic effect of beta adrenoceptor blockers in angina pectoris can be ascribed to an inhibition of beta1 receptor mediated stimulation of heart rate and myocardial contractility, resulting in an improved oxygen supply-demand balance in the myocardium. When given in equipotent beta1 blocking doses, the nonselective blocker propranolol and the beta1 selective blocker metoprolol differ markedly as regards inhibition of adrenaline induced beta2 mediated vasodilatation. Only propranolol will inhibit this effect. After propranolol, adrenaline therefore elicits a haemodynamic effect pattern characterized by high peripheral vascular resistance, high arterial blood pressure, low cardiac output and increased cardiac size. In view of these findings it is suggested that a beta1 selective blocker may be a more efficient antianginal agent than a nonselective blocker in those patients in which the anginal attack is associated with a significant release of adrenaline. The clinical relevance of this hypothesis has not been tested.", "contents": "Mode of action of beta blockers in angina pectoris. The therapeutic effect of beta adrenoceptor blockers in angina pectoris can be ascribed to an inhibition of beta1 receptor mediated stimulation of heart rate and myocardial contractility, resulting in an improved oxygen supply-demand balance in the myocardium. When given in equipotent beta1 blocking doses, the nonselective blocker propranolol and the beta1 selective blocker metoprolol differ markedly as regards inhibition of adrenaline induced beta2 mediated vasodilatation. Only propranolol will inhibit this effect. After propranolol, adrenaline therefore elicits a haemodynamic effect pattern characterized by high peripheral vascular resistance, high arterial blood pressure, low cardiac output and increased cardiac size. In view of these findings it is suggested that a beta1 selective blocker may be a more efficient antianginal agent than a nonselective blocker in those patients in which the anginal attack is associated with a significant release of adrenaline. The clinical relevance of this hypothesis has not been tested."}
{"id": "PMID:13496", "title": "Haemodynamic effects of different beta blockers in angina pectoris.", "content": "Beta-blocking agents with partial agonist activity seem to reduce heart rate at rest slightly less than those without this property. Cardio-selective drugs have no effect on stroke volume at rest contrary to the non-selective ones which will reduce it somewhat. This difference is abolished during exercise. The only difference seen during work between different beta-blockers is the effect on the peripheral vascular resistance. The selective drugs lower the arterial pressure with unchanged resistance.", "contents": "Haemodynamic effects of different beta blockers in angina pectoris. Beta-blocking agents with partial agonist activity seem to reduce heart rate at rest slightly less than those without this property. Cardio-selective drugs have no effect on stroke volume at rest contrary to the non-selective ones which will reduce it somewhat. This difference is abolished during exercise. The only difference seen during work between different beta-blockers is the effect on the peripheral vascular resistance. The selective drugs lower the arterial pressure with unchanged resistance."}
{"id": "PMID:13492", "title": "Inorganic photoreduction of nicotinamide adenine dinucleotide phosphate. I. Photoreduction by certain oxide semiconductors in the near ultraviolet.", "content": "The action of chloroplasts in the light reactions of photosynthesis is the reduction of NADP to NADPH and phosphorylation of ADP to ATP by light energy. According to the electron theory of catalysis of photosynthesis, these functions of chloroplasts can be mimicked by any inorganic semiconductors. This paper reports that with ZnO instead of chloroplasts NADP can be photoreduced to NADPH in the near ultraviolet.", "contents": "Inorganic photoreduction of nicotinamide adenine dinucleotide phosphate. I. Photoreduction by certain oxide semiconductors in the near ultraviolet. The action of chloroplasts in the light reactions of photosynthesis is the reduction of NADP to NADPH and phosphorylation of ADP to ATP by light energy. According to the electron theory of catalysis of photosynthesis, these functions of chloroplasts can be mimicked by any inorganic semiconductors. This paper reports that with ZnO instead of chloroplasts NADP can be photoreduced to NADPH in the near ultraviolet."}
{"id": "PMID:13497", "title": "Observations in man of hypoglycaemia during selective and non-selective beta-blockade.", "content": "The acute hypoglycaemic reaction is accompanied by a rise in systolic and a slight fall in diastolic blood pressure and a tachycardia. In contrast, during beta-blockade with propranolol there is a rise of both systolic and diastolic blood pressures and bradycardia. Restoration of blood glucose to normal is delayed. With metoprolol there is a lesser increase in diastolic blood pressure and a slight tachycardia. Restoration of the blood glucose to normal is little delayed. When patients liable to hypoglycaemia require a beta-blocking agent, it is suggested that a selective blocker such as metoprolol should be used.", "contents": "Observations in man of hypoglycaemia during selective and non-selective beta-blockade. The acute hypoglycaemic reaction is accompanied by a rise in systolic and a slight fall in diastolic blood pressure and a tachycardia. In contrast, during beta-blockade with propranolol there is a rise of both systolic and diastolic blood pressures and bradycardia. Restoration of blood glucose to normal is delayed. With metoprolol there is a lesser increase in diastolic blood pressure and a slight tachycardia. Restoration of the blood glucose to normal is little delayed. When patients liable to hypoglycaemia require a beta-blocking agent, it is suggested that a selective blocker such as metoprolol should be used."}
{"id": "PMID:13499", "title": "Dopamine-sensitive adenylate cyclase: location in substantia nigra.", "content": "A dopamine-sensitive adenylate cyclase with characteristics similar to those measured in the striatum is present in the rat substantia nigra. Destruction of dopamine cell bodies by intranigral 6-hydroxydopamine application failed to abolish the response of nigral adenylate cyclase to dopamine. In contrast, brain hemitransection between the striatum and substantia nigra, or a more circumscribed lesion of striatonigral pathways, abolished the dopamine stimulation of adenylate cyclase in the substantia nigra. These results suggest that dopamine receptors within the substantia nigra are not located on dopamine cell bodies but are associated with a pathway, containing gamma-aminobutyric acid or substance P, which projects from forebrain structures to the substantia nigra.", "contents": "Dopamine-sensitive adenylate cyclase: location in substantia nigra. A dopamine-sensitive adenylate cyclase with characteristics similar to those measured in the striatum is present in the rat substantia nigra. Destruction of dopamine cell bodies by intranigral 6-hydroxydopamine application failed to abolish the response of nigral adenylate cyclase to dopamine. In contrast, brain hemitransection between the striatum and substantia nigra, or a more circumscribed lesion of striatonigral pathways, abolished the dopamine stimulation of adenylate cyclase in the substantia nigra. These results suggest that dopamine receptors within the substantia nigra are not located on dopamine cell bodies but are associated with a pathway, containing gamma-aminobutyric acid or substance P, which projects from forebrain structures to the substantia nigra."}
{"id": "PMID:13501", "title": "Uterine and cardiovascular effects of beta2-selective sympathomimetic drugs administered as an intravenous infusion.", "content": "The uterine and cardiovascular effects of fenoterol, hexoprenaline, ritodrine and salbutamol, given as intravenous infusions in equivalent and therapeutic dosages in oxytocin-induced labour, were studied and compared. All the drugs were effective in reducing the uterine activity to less than 30% of the original. The effect on the cardiovascular system was to produce a moderate tachycardia and a widening of the pulse pressure by raising the systolic and decreasing the diastolic blood pressures.", "contents": "Uterine and cardiovascular effects of beta2-selective sympathomimetic drugs administered as an intravenous infusion. The uterine and cardiovascular effects of fenoterol, hexoprenaline, ritodrine and salbutamol, given as intravenous infusions in equivalent and therapeutic dosages in oxytocin-induced labour, were studied and compared. All the drugs were effective in reducing the uterine activity to less than 30% of the original. The effect on the cardiovascular system was to produce a moderate tachycardia and a widening of the pulse pressure by raising the systolic and decreasing the diastolic blood pressures."}
{"id": "PMID:13502", "title": "Studies of the pharmacology of a new antidepressant, S1694.", "content": "A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect.", "contents": "Studies of the pharmacology of a new antidepressant, S1694. A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect."}
{"id": "PMID:13503", "title": "Enzymatic and hemodynamic changes after short term hepatic outflow occlusion in the dog.", "content": "In normal mongrel dogs, outflow occlusion of 15 or 30 minutes duration was produced by clamping both the suprahepatic and suprarenal portions of the vena cava. One dog died immediately after release of occlusion; two dogs died from recurrent hypotension between six and 24 hours postoperatively. The other five dogs survived for three days, at which time an autopsy was done. During outflow occlusion, the blood pressure fell in all dogs, as did the central venous pressure. The pulse rate decreased during, and after, occlusion but toward a tendency of gradual recovery. A significant drop in pH and base excess of arterial blood was seen after occlusion. Although a steady, but not substantial, increase in hemoglobin and hematocrit values was noted, there were no remarkable changes in the blood coagulation system. Significant increases in serum glutamic-oxalacetic transaminase, glutamic-pyruvic-transaminase, lactic dehydrogenase, acid phosphatase and beta-glucuronidase activities were observed from immediately after release of occlusion, but alkaline phosphatase values increased much later than did these. Thus, hepatic outflow occlusion, even if it is short, seems to be dangerous in the dog, since it produces hypotension, metabolic acidosis and diffuse damage as well as disruption of the parenchyma of the liver.", "contents": "Enzymatic and hemodynamic changes after short term hepatic outflow occlusion in the dog. In normal mongrel dogs, outflow occlusion of 15 or 30 minutes duration was produced by clamping both the suprahepatic and suprarenal portions of the vena cava. One dog died immediately after release of occlusion; two dogs died from recurrent hypotension between six and 24 hours postoperatively. The other five dogs survived for three days, at which time an autopsy was done. During outflow occlusion, the blood pressure fell in all dogs, as did the central venous pressure. The pulse rate decreased during, and after, occlusion but toward a tendency of gradual recovery. A significant drop in pH and base excess of arterial blood was seen after occlusion. Although a steady, but not substantial, increase in hemoglobin and hematocrit values was noted, there were no remarkable changes in the blood coagulation system. Significant increases in serum glutamic-oxalacetic transaminase, glutamic-pyruvic-transaminase, lactic dehydrogenase, acid phosphatase and beta-glucuronidase activities were observed from immediately after release of occlusion, but alkaline phosphatase values increased much later than did these. Thus, hepatic outflow occlusion, even if it is short, seems to be dangerous in the dog, since it produces hypotension, metabolic acidosis and diffuse damage as well as disruption of the parenchyma of the liver."}
{"id": "PMID:13504", "title": "A review of recent advances in vascular smooth muscle pharmacology.", "content": "An understanding of the physiology of vascular smooth muscle and knowledge of the reaction of such muscle to certain drugs are essential for the development of a means of treating cerebral arterial spasm. The role of cyclic nucleotides in vascular smooth muscle activity is reviewed and possible therapeutic approaches are listed. Probably the safest and most effective treatment would be 1) stimulation of the adenyl cyclase-cyclic adenosine monophosphate system by a beta(2)-adrenergic drug combined with 2) inhibition of the phosphodiesterase system.", "contents": "A review of recent advances in vascular smooth muscle pharmacology. An understanding of the physiology of vascular smooth muscle and knowledge of the reaction of such muscle to certain drugs are essential for the development of a means of treating cerebral arterial spasm. The role of cyclic nucleotides in vascular smooth muscle activity is reviewed and possible therapeutic approaches are listed. Probably the safest and most effective treatment would be 1) stimulation of the adenyl cyclase-cyclic adenosine monophosphate system by a beta(2)-adrenergic drug combined with 2) inhibition of the phosphodiesterase system."}
{"id": "PMID:13505", "title": "Bioavailability and generic prescribing.", "content": "Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology. Factors that can alter drug absorption from solutions (pH, partition coefficient, container impurities, contact time, etc.) are noted, and cases in which bioavailability problems should be considered as causes of therapeutic failure are discussed. Various attitudes representing pharmaceutical companies, the federal government, pharmacists, consumers and physicians toward the related problems of bioinequivalence and generic prescribing are examined. Techniques for in vivo and in vitro drug testing and for establishing uniform conditions of drug manufacture and storage can contribute to identification and minimization of bioavailability problems. A rational program based on a combination of such techniques could, ultimately, lead to establishment of the terms \"generic equivalency\" and \"therapeutic equivalency\" as synonymous.", "contents": "Bioavailability and generic prescribing. Although oral drug bioinequivalence has been attributed to a number of causes (excipients, dosage form, variation in dissolution time, and aging) less is known about bioavailability problems of topical medications in ophthalmology. Factors that can alter drug absorption from solutions (pH, partition coefficient, container impurities, contact time, etc.) are noted, and cases in which bioavailability problems should be considered as causes of therapeutic failure are discussed. Various attitudes representing pharmaceutical companies, the federal government, pharmacists, consumers and physicians toward the related problems of bioinequivalence and generic prescribing are examined. Techniques for in vivo and in vitro drug testing and for establishing uniform conditions of drug manufacture and storage can contribute to identification and minimization of bioavailability problems. A rational program based on a combination of such techniques could, ultimately, lead to establishment of the terms \"generic equivalency\" and \"therapeutic equivalency\" as synonymous."}
{"id": "PMID:13510", "title": "Total body potassium in cor pulmonale.", "content": "Total body potassium was measured in 12 patients with cor pulmonale, by determination of potassium-40, a naturally occurring radioisotope. In all subjects the observed value of total body potassium showed no significant depletion when compared with that predicted from height and age. All previous studies in similar groups of patients have been confined to the estimation of exchangeable potassium by the technique of isotope dilution. Results using the latter technique have shown gross potassium depletion. It is suggested that the apparent disparity between total body potassium and exchangeable potassium could be explained by the requirement for a longer equilibration period when using isotope dilution techniques in patients who are in chronic hypoxaemic state.", "contents": "Total body potassium in cor pulmonale. Total body potassium was measured in 12 patients with cor pulmonale, by determination of potassium-40, a naturally occurring radioisotope. In all subjects the observed value of total body potassium showed no significant depletion when compared with that predicted from height and age. All previous studies in similar groups of patients have been confined to the estimation of exchangeable potassium by the technique of isotope dilution. Results using the latter technique have shown gross potassium depletion. It is suggested that the apparent disparity between total body potassium and exchangeable potassium could be explained by the requirement for a longer equilibration period when using isotope dilution techniques in patients who are in chronic hypoxaemic state."}
{"id": "PMID:13511", "title": "Arterial blood gas tensions, hydrogen ion, and electroencephalogram during sleep in patients with chronic ventilatory failure.", "content": "We have studied arterial PO2, PCO2, and hydrogen ion and electroencephalogram during sleep in 10 patients with stable severe chronic respiratory failure. As a group the patients slept badly. Sleep was associated with a worsening of hypoxia and no significant change in PCO2 and H+. Two patients were restudied, receiving oxygen therapy overnight. Both had improved sleep but one, who had an intact hypoxic drive to breathing, developed marked hypercapnia and acidosis when his PO2 was restored to normal during sleep; the other, who had no hypoxic drive to breathing, developed no more hypercapnia or acidosis during sleep when breathing oxygen than when breathing air. Oxygen therapy may improve sleep disturbance in these patients, but its effect on the drive to breathing during sleep should be considered if severe hypercapnia and acidosis are to be avoided.", "contents": "Arterial blood gas tensions, hydrogen ion, and electroencephalogram during sleep in patients with chronic ventilatory failure. We have studied arterial PO2, PCO2, and hydrogen ion and electroencephalogram during sleep in 10 patients with stable severe chronic respiratory failure. As a group the patients slept badly. Sleep was associated with a worsening of hypoxia and no significant change in PCO2 and H+. Two patients were restudied, receiving oxygen therapy overnight. Both had improved sleep but one, who had an intact hypoxic drive to breathing, developed marked hypercapnia and acidosis when his PO2 was restored to normal during sleep; the other, who had no hypoxic drive to breathing, developed no more hypercapnia or acidosis during sleep when breathing oxygen than when breathing air. Oxygen therapy may improve sleep disturbance in these patients, but its effect on the drive to breathing during sleep should be considered if severe hypercapnia and acidosis are to be avoided."}
{"id": "PMID:13516", "title": "Studies on the properties of the immunologically effective anti-tumor substance from spleen cells of tumor-resistant rats.", "content": "The influence of physical and chemical treatments upon the immunologically effective subcellular fractions (5,000 X g supernatant and 105,000 X g sediment), which were prepared from the spleen cells of Yoshida sarcoma (YS)-resistant Donryu rats, was studied. The immunological activity of the 5,000 X g supernatant was stable to heating at 80 degrees C for 30 min. It was stable to alkali (pH 10) and less stable to acid (pH 2). It was labile to a ten-day storage at 4 degrees C, but relatively stable to a 30-day storage at -20 degrees C. When the 105,000 X g sediment was lyophilized and stored at -20 degrees C for 95 days, its immunological activity was well maintained. It was labile to 95% ethanol, 90% phenol and 2 M NaNO2, but relatively stable to 10% as well as 100% acetone, 10% phenol and 10% ethanol. It was labile to 0.1 M NaIO4 and relatively stable to 0.1 M K2Cr2O7 solution. It was labile to RNase but relatively stable to DNase.", "contents": "Studies on the properties of the immunologically effective anti-tumor substance from spleen cells of tumor-resistant rats. The influence of physical and chemical treatments upon the immunologically effective subcellular fractions (5,000 X g supernatant and 105,000 X g sediment), which were prepared from the spleen cells of Yoshida sarcoma (YS)-resistant Donryu rats, was studied. The immunological activity of the 5,000 X g supernatant was stable to heating at 80 degrees C for 30 min. It was stable to alkali (pH 10) and less stable to acid (pH 2). It was labile to a ten-day storage at 4 degrees C, but relatively stable to a 30-day storage at -20 degrees C. When the 105,000 X g sediment was lyophilized and stored at -20 degrees C for 95 days, its immunological activity was well maintained. It was labile to 95% ethanol, 90% phenol and 2 M NaNO2, but relatively stable to 10% as well as 100% acetone, 10% phenol and 10% ethanol. It was labile to 0.1 M NaIO4 and relatively stable to 0.1 M K2Cr2O7 solution. It was labile to RNase but relatively stable to DNase."}
{"id": "PMID:13520", "title": "Minor and trace sterols in marine invertebrates. 1. General methods of analysis.", "content": "3beta-Hydroxy sterols occurring at a concentration of at least 0.001% of the sterol mixtures of Pseudoplexaura porosa and Plexaura homomalla have been fractionated using a series of refined techniques and subsequently analyzed using combined gas chromatography-mass spectrometry (GC-MS) in the development of a procedure for examining the minor and trace components of marine sterol mixtures. A total of 49 sterols were found which spanned a molecular weight range of 274 to 440. In addition delta4-3-keto analogs of cholesterol, 24-methylcholesterol and gorgosterol were found in the extracts of P. homomalla. Initial separation of various natural sterol-containing conjugates and free sterols was found to have a number of advantages. Fractional digitonin precipitation and alumina column chromatography were found to possess greater sterol separation abilities than previously recognized. Many of the minor sterols were found to possess novel structures including a series of short side chain sterols, 19-nor sterols, 5beta-stanols and 4-monomethyl sterols for which structure elucidation work is continuing.", "contents": "Minor and trace sterols in marine invertebrates. 1. General methods of analysis. 3beta-Hydroxy sterols occurring at a concentration of at least 0.001% of the sterol mixtures of Pseudoplexaura porosa and Plexaura homomalla have been fractionated using a series of refined techniques and subsequently analyzed using combined gas chromatography-mass spectrometry (GC-MS) in the development of a procedure for examining the minor and trace components of marine sterol mixtures. A total of 49 sterols were found which spanned a molecular weight range of 274 to 440. In addition delta4-3-keto analogs of cholesterol, 24-methylcholesterol and gorgosterol were found in the extracts of P. homomalla. Initial separation of various natural sterol-containing conjugates and free sterols was found to have a number of advantages. Fractional digitonin precipitation and alumina column chromatography were found to possess greater sterol separation abilities than previously recognized. Many of the minor sterols were found to possess novel structures including a series of short side chain sterols, 19-nor sterols, 5beta-stanols and 4-monomethyl sterols for which structure elucidation work is continuing."}
{"id": "PMID:13523", "title": "Detection of serum-blocking factors by inhibition of allorosette formation in rats with long-surviving renal allografts following short-term postoperative ALS treatment.", "content": "Thirty-nine (LEW x BN)F1 kidneys were transplanted to LEW rats. Twenty-four untreated recipients survived for a mean time of 16.1 +/- 1.7 days (group 1). Fifteen recipients received 4 ml of antilymphocytic serum per rat (group 3). In the last group 10 recipients survived for more than 4 months. The spleen cells of these permanently surviving 10 rats were obtained by splenectomy and used in a graft-versus-host assay, and this assay showed that the reactivity of these cells was normal. Following splenectomy the animals were given an (LEW x BN)F1 skin allograft, followed 18 days by a second. After another 18 days (LEW x Buf)F1 \"third party\" skin allografts were transplanted to the same animals. Animals of group 2 rejected their first grafts with a mean survival time of 12.2 +/- 1.2 days, whereas the second grafts were rejected normally as were the third party grafts. Attempts were made to detect lymphocytotoxic antibodies and haemagglutinins before and after the transplantation of skin grafts and none could be found up to day 53. The sera of group 2 inhibited allorosette formation by 38%. This serum-blocking factor was donor specific. It is probable that the survival of the kidney transplants following antilymphocytic serum treatment was brought about by the development of blocking antibodies.", "contents": "Detection of serum-blocking factors by inhibition of allorosette formation in rats with long-surviving renal allografts following short-term postoperative ALS treatment. Thirty-nine (LEW x BN)F1 kidneys were transplanted to LEW rats. Twenty-four untreated recipients survived for a mean time of 16.1 +/- 1.7 days (group 1). Fifteen recipients received 4 ml of antilymphocytic serum per rat (group 3). In the last group 10 recipients survived for more than 4 months. The spleen cells of these permanently surviving 10 rats were obtained by splenectomy and used in a graft-versus-host assay, and this assay showed that the reactivity of these cells was normal. Following splenectomy the animals were given an (LEW x BN)F1 skin allograft, followed 18 days by a second. After another 18 days (LEW x Buf)F1 \"third party\" skin allografts were transplanted to the same animals. Animals of group 2 rejected their first grafts with a mean survival time of 12.2 +/- 1.2 days, whereas the second grafts were rejected normally as were the third party grafts. Attempts were made to detect lymphocytotoxic antibodies and haemagglutinins before and after the transplantation of skin grafts and none could be found up to day 53. The sera of group 2 inhibited allorosette formation by 38%. This serum-blocking factor was donor specific. It is probable that the survival of the kidney transplants following antilymphocytic serum treatment was brought about by the development of blocking antibodies."}
{"id": "PMID:13521", "title": "Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia.", "content": "As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH.", "contents": "Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH."}
{"id": "PMID:13525", "title": "Deficiency in the thymus-dependent immunity in \"lethargic\" mutant mice.", "content": "T cell function of \"lethargic\" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests. At 15 to 30 days of age, the mutant mice did not reject skin allografts, but by 45 days of age their response was normal. Spleen cells from 24-day-old mutant donors demonstrated delayed appearance of graft-versus-host induced splenomegaly in F1 recipients. Implications of these results in understanding the immunological status of lethargic mice were considered.", "contents": "Deficiency in the thymus-dependent immunity in \"lethargic\" mutant mice. T cell function of \"lethargic\" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests. At 15 to 30 days of age, the mutant mice did not reject skin allografts, but by 45 days of age their response was normal. Spleen cells from 24-day-old mutant donors demonstrated delayed appearance of graft-versus-host induced splenomegaly in F1 recipients. Implications of these results in understanding the immunological status of lethargic mice were considered."}
{"id": "PMID:13526", "title": "Epidemiologic study of arboviruses in the Arba-Minch district of Ethiopia.", "content": "A yellow fever outbreak occurred in 1966 in Arba-Minch District, east of Abaya Lake, in Ethiopia. The present study was undertaken to assess the southern limits of that epidemic and to contribute to the inventory of arboviruses and potential vectors in that area. In the highlands 90 sera were collected, in the lowlands 140. With regard to Group B the sera reacted only with yellow fever, Wesselsbron and Spondweni antigens. In the highlands 17.8%, in the lowlands 22.2%, were positive for group B. In two sera only the titers against yellow fever were high. The absence of reactivity to West Nile virus was striking. A wide variety of Culicidae was present and differentiated. Potential or proven vectors were collected. At the time of the survey yellow fever was not active in the region. Because of an only partly immune human population, and of the presence of non-immune monkeys and some potential vectors, the area should, however, be considered to be receptive.", "contents": "Epidemiologic study of arboviruses in the Arba-Minch district of Ethiopia. A yellow fever outbreak occurred in 1966 in Arba-Minch District, east of Abaya Lake, in Ethiopia. The present study was undertaken to assess the southern limits of that epidemic and to contribute to the inventory of arboviruses and potential vectors in that area. In the highlands 90 sera were collected, in the lowlands 140. With regard to Group B the sera reacted only with yellow fever, Wesselsbron and Spondweni antigens. In the highlands 17.8%, in the lowlands 22.2%, were positive for group B. In two sera only the titers against yellow fever were high. The absence of reactivity to West Nile virus was striking. A wide variety of Culicidae was present and differentiated. Potential or proven vectors were collected. At the time of the survey yellow fever was not active in the region. Because of an only partly immune human population, and of the presence of non-immune monkeys and some potential vectors, the area should, however, be considered to be receptive."}
{"id": "PMID:13530", "title": "[Experience with the use of viadril anesthesia].", "content": "Based on experimental and clinical findings the authors concluded that a combination of viadril with neuroleptanalgesics shows a number of advantages over purely viadril anesthesia or its combination with other drugs for inhalation and intravenous anesthesia. The technic of thalmonal-viadril anesthesia is reported.", "contents": "[Experience with the use of viadril anesthesia]. Based on experimental and clinical findings the authors concluded that a combination of viadril with neuroleptanalgesics shows a number of advantages over purely viadril anesthesia or its combination with other drugs for inhalation and intravenous anesthesia. The technic of thalmonal-viadril anesthesia is reported."}
{"id": "PMID:13537", "title": "[Adaptation to oxygen breathing].", "content": "Controlled, dosed, uninterrupted and continuous oxygen treatment was applied in 63 patients with global respiratory insufficiency, through a nasopharyngeal catheter in concentrations to 30 per cent. PaO2, is elevated with and average of 12 mm mercury column after 30 minutes 25% oxygen breathing and PaCO2--at an average of 8 mm mercury column. PaO2 level was kept after 24 hours whereas PaCO2 decreased at an average of 4 mm mercury column. Besides, respiration and pulse rate are decelerated, secondary polyglobulia decreases, cardiac and renal function is improved. Those changes are interpreted as patients' adaptation to oxygen breathing. The adaptation to oxygen breathing decreases the danger of critical intensification of the respiratory depression in the course of the treatment and conditions for a successful application of O2 treatment at home are created.", "contents": "[Adaptation to oxygen breathing]. Controlled, dosed, uninterrupted and continuous oxygen treatment was applied in 63 patients with global respiratory insufficiency, through a nasopharyngeal catheter in concentrations to 30 per cent. PaO2, is elevated with and average of 12 mm mercury column after 30 minutes 25% oxygen breathing and PaCO2--at an average of 8 mm mercury column. PaO2 level was kept after 24 hours whereas PaCO2 decreased at an average of 4 mm mercury column. Besides, respiration and pulse rate are decelerated, secondary polyglobulia decreases, cardiac and renal function is improved. Those changes are interpreted as patients' adaptation to oxygen breathing. The adaptation to oxygen breathing decreases the danger of critical intensification of the respiratory depression in the course of the treatment and conditions for a successful application of O2 treatment at home are created."}
{"id": "PMID:13541", "title": "[Postural hypotension: pathophysiology and clinical features (author's transl)].", "content": "Circulatory regulation in response to postural changes follows mechanical rules, whereby the shifts in volume in the various organs of the body play an essential role. The change from the horizontal to the vertical position is accompanied by a decrease in pressure above the hydrostatic neutral point, i.e. in the cephalic vessels, whereas the capacious vessels in the caudal region are dilated and the venous return becomes sluggish. As a consequence of the different time courses followed by the various circulatory parameters in the wake of counter-regulatory measures, a distinction can be made between an early orthostatic instant regulatory response and a late orthostatic response. Prominent clinical features do not necessarily always consist of non-systemic dizziness, tinnitus, pallor cold sweat and, finally, orthostatic collapse, but general subjective symptoms such as deafness and tingling of the extremities, a chilly sensation and cardiac symptoms may frequently predominante. In the case of development of an autonomic neurotic symptom complex, psychoautonomic symptoms such as general sleep disturbance are observed. Apart from investigations carried out on a surgical tilting table in general practice, other procedures such as the Valsalva manoeuvre, the squatting test and, in most cases, the erect test are performed. Broadly speaking four different reaction types can be distinguished amongst cases of postural hypotension. Drugs with different therapeutic actions are selectively administered according to the pathophysiological characteristics of the individual patient and the sympathetic adrenal counter-regulatory response. Medico-mechanical measures and physical training should not be neglected.", "contents": "[Postural hypotension: pathophysiology and clinical features (author's transl)]. Circulatory regulation in response to postural changes follows mechanical rules, whereby the shifts in volume in the various organs of the body play an essential role. The change from the horizontal to the vertical position is accompanied by a decrease in pressure above the hydrostatic neutral point, i.e. in the cephalic vessels, whereas the capacious vessels in the caudal region are dilated and the venous return becomes sluggish. As a consequence of the different time courses followed by the various circulatory parameters in the wake of counter-regulatory measures, a distinction can be made between an early orthostatic instant regulatory response and a late orthostatic response. Prominent clinical features do not necessarily always consist of non-systemic dizziness, tinnitus, pallor cold sweat and, finally, orthostatic collapse, but general subjective symptoms such as deafness and tingling of the extremities, a chilly sensation and cardiac symptoms may frequently predominante. In the case of development of an autonomic neurotic symptom complex, psychoautonomic symptoms such as general sleep disturbance are observed. Apart from investigations carried out on a surgical tilting table in general practice, other procedures such as the Valsalva manoeuvre, the squatting test and, in most cases, the erect test are performed. Broadly speaking four different reaction types can be distinguished amongst cases of postural hypotension. Drugs with different therapeutic actions are selectively administered according to the pathophysiological characteristics of the individual patient and the sympathetic adrenal counter-regulatory response. Medico-mechanical measures and physical training should not be neglected."}
{"id": "PMID:13542", "title": "[Early clinical symptoms and therapy of haemorrhages in old age (author's transl)].", "content": "There is hardly a bleeding, where the extrinsic-and/or the intrinsic-system of the coagulation does not take part in. Haemorrhages represent a symptom only, and it is always to clear, if they are come from a local process of illness or from a general tendency of haemorrhage. There is point to the clinical differences of great bleeding (coagulopathy) and bleedings like points (the causes lie in the thrombocytes or in a vascular damage). The early clinical symptoms and the therapy of haemorrhages by the old human without the primary disturbance of the coagulate-system are discussed.", "contents": "[Early clinical symptoms and therapy of haemorrhages in old age (author's transl)]. There is hardly a bleeding, where the extrinsic-and/or the intrinsic-system of the coagulation does not take part in. Haemorrhages represent a symptom only, and it is always to clear, if they are come from a local process of illness or from a general tendency of haemorrhage. There is point to the clinical differences of great bleeding (coagulopathy) and bleedings like points (the causes lie in the thrombocytes or in a vascular damage). The early clinical symptoms and the therapy of haemorrhages by the old human without the primary disturbance of the coagulate-system are discussed."}
{"id": "PMID:13543", "title": "[Duodenogastric reflux and anastomosis abscess. Experimental study].", "content": "Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of reflux and stasis potentiate, resulting in a high frequency of ulcer (greater than 90%). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (p less than o,o1); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. -- In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis.", "contents": "[Duodenogastric reflux and anastomosis abscess. Experimental study]. Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of reflux and stasis potentiate, resulting in a high frequency of ulcer (greater than 90%). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (p less than o,o1); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. -- In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis."}
{"id": "PMID:13547", "title": "[Histopathological study of the mosquito-bite infiltrate in patients with various underlying diseases and different medications].", "content": "A histologic study was carried out on tissue-reactions after insect bits in 9 patients with various primary diseases. The clinical and cellular reactions to the bite in the epidermis varied, according to the length, intensity of toxity of the insect bit. The dermal infiltrate was similar in almost all cases and corresponded to a cellular immunologic reaction of the early or late type, as is also to be seen in trichophytin and tuberculin-reactions. Tere was clearly no relationship between the character of the dermal infiltrate and the basic disease. We also found no change in the dermal infiltrate due to special medicaments. Even corticosteroids did not suppress the dermal cellular reactions. There was also a striking absence of eosinophil leucocytes in the dermal infiltrate.", "contents": "[Histopathological study of the mosquito-bite infiltrate in patients with various underlying diseases and different medications]. A histologic study was carried out on tissue-reactions after insect bits in 9 patients with various primary diseases. The clinical and cellular reactions to the bite in the epidermis varied, according to the length, intensity of toxity of the insect bit. The dermal infiltrate was similar in almost all cases and corresponded to a cellular immunologic reaction of the early or late type, as is also to be seen in trichophytin and tuberculin-reactions. Tere was clearly no relationship between the character of the dermal infiltrate and the basic disease. We also found no change in the dermal infiltrate due to special medicaments. Even corticosteroids did not suppress the dermal cellular reactions. There was also a striking absence of eosinophil leucocytes in the dermal infiltrate."}
{"id": "PMID:13548", "title": "Non-equivalence and inverse allosteric response of the alpha and beta chains in haemoglobins. An electron spin resonance study of NO-ligated Hb Kansas.", "content": "The electron spin resonance (ESR) spectra of 15NO- and 14NO-ligated Hb Kansas have been measured at 77 K in the range of pH 5 TO 10. At low pH the ESR spectrum is the composite of a type I and a type II spectrum which changes to another composite of type I and type II spectrum at high pH. For the definition of type I and type II spectra and the correlation of these types with two tertiary conformation states see Overkamp et al., Z. Naturforsch. 31 c, 524 [1976]. Both, the type I and the type II spectra observed at low and high pH respectively are different with regard to g-tensors and hyperfine-splitting constants. Therefore at intermediate pH values the ESR spectra of NO-Hb Kansas are the composites of four spectral components. The assignments of the four spectral components to the alpha and the beta chains are arrived at from the comparison of the ESR spectra of the alpha2Mmet beta2NO and of the alpha2MNObeta2NO species of Hb M Iwate. alpha and beta chains are both characterized by a pH-dependent spectral transition from a type I to a type II spectrum. The chains are non-equivalent with regard to both the type I and the type II spectra. The type I spectra assigned to the alpha and the beta chains are characterized by G*ZZ=2.0095 with a hyperfine splitting of alpha*ZZ(15NO)=2.36 mT and gZZ-2.0085 with a hyperfine splitting of aZZ(15NO)=2.41 mT respectively. The type II spectra assigned to the alpha and the beta chains are characterized by g*'ZZ-2.005 and a hyperfine splitting of alpha*'ZZ(15NO)-3.07 mT and g'ZZ-2.005 and a hyperfine splitting of alpha'ZZ(15NO)=3.31 mT. The change of the hyperfine splitting at gZZ during the transition from type I to type II corresponds to an increase of the spin density at the NO by about 25% in both types of chains. Comparison of type I spectra of the NO-ligated alpha and beta chains respectively demonstrates that the spin density at the NO is larger in the beta chains that in the alpha chains. The spectral types are correlated with functional states defined by the kinetics of N0-binding. Binding of inosital hexaphosphate has no influence on the ESR spectra in the whole range of pH as it is expected if NO-Hb Kandas is in the quaternary T structure.", "contents": "Non-equivalence and inverse allosteric response of the alpha and beta chains in haemoglobins. An electron spin resonance study of NO-ligated Hb Kansas. The electron spin resonance (ESR) spectra of 15NO- and 14NO-ligated Hb Kansas have been measured at 77 K in the range of pH 5 TO 10. At low pH the ESR spectrum is the composite of a type I and a type II spectrum which changes to another composite of type I and type II spectrum at high pH. For the definition of type I and type II spectra and the correlation of these types with two tertiary conformation states see Overkamp et al., Z. Naturforsch. 31 c, 524 [1976]. Both, the type I and the type II spectra observed at low and high pH respectively are different with regard to g-tensors and hyperfine-splitting constants. Therefore at intermediate pH values the ESR spectra of NO-Hb Kansas are the composites of four spectral components. The assignments of the four spectral components to the alpha and the beta chains are arrived at from the comparison of the ESR spectra of the alpha2Mmet beta2NO and of the alpha2MNObeta2NO species of Hb M Iwate. alpha and beta chains are both characterized by a pH-dependent spectral transition from a type I to a type II spectrum. The chains are non-equivalent with regard to both the type I and the type II spectra. The type I spectra assigned to the alpha and the beta chains are characterized by G*ZZ=2.0095 with a hyperfine splitting of alpha*ZZ(15NO)=2.36 mT and gZZ-2.0085 with a hyperfine splitting of aZZ(15NO)=2.41 mT respectively. The type II spectra assigned to the alpha and the beta chains are characterized by g*'ZZ-2.005 and a hyperfine splitting of alpha*'ZZ(15NO)-3.07 mT and g'ZZ-2.005 and a hyperfine splitting of alpha'ZZ(15NO)=3.31 mT. The change of the hyperfine splitting at gZZ during the transition from type I to type II corresponds to an increase of the spin density at the NO by about 25% in both types of chains. Comparison of type I spectra of the NO-ligated alpha and beta chains respectively demonstrates that the spin density at the NO is larger in the beta chains that in the alpha chains. The spectral types are correlated with functional states defined by the kinetics of N0-binding. Binding of inosital hexaphosphate has no influence on the ESR spectra in the whole range of pH as it is expected if NO-Hb Kandas is in the quaternary T structure."}
{"id": "PMID:13549", "title": "Kinetic analysis of the catalytic properties of peptides in ester hydrolysis.", "content": "The catalytic properties of peptides containing histidine, cysteine and aspartic acid in ester hydrolysis were studied. Saturation kinetics were found for the reaction of p-nitrophenyl acetate (NPA) with Z-His-Ala-Asp-Gly-Cys-NH2 and Z-His-Ala-Gly-Cly-Cys-NH2. The Br\u00f6nsted equation for the hydrolysis of tert-butyloxcarbonyl-L-alanine-p-nitrophenylester (Bos-Ala-ONp) catalyzed by simple imidazole and SH-compounds was determined. The catalytic behaviour of the peptides in ester hydrolysis could not be described by the Br\u00f6nsted equations for imidazole o thiole catalyzed hydrolysis of NPA and Boc-Ala-ONp. The pH dependence of the rate constants of the catalyzed ester hydrolysis gave no linear plots in 1/k versus H+ diagrrams.", "contents": "Kinetic analysis of the catalytic properties of peptides in ester hydrolysis. The catalytic properties of peptides containing histidine, cysteine and aspartic acid in ester hydrolysis were studied. Saturation kinetics were found for the reaction of p-nitrophenyl acetate (NPA) with Z-His-Ala-Asp-Gly-Cys-NH2 and Z-His-Ala-Gly-Cly-Cys-NH2. The Br\u00f6nsted equation for the hydrolysis of tert-butyloxcarbonyl-L-alanine-p-nitrophenylester (Bos-Ala-ONp) catalyzed by simple imidazole and SH-compounds was determined. The catalytic behaviour of the peptides in ester hydrolysis could not be described by the Br\u00f6nsted equations for imidazole o thiole catalyzed hydrolysis of NPA and Boc-Ala-ONp. The pH dependence of the rate constants of the catalyzed ester hydrolysis gave no linear plots in 1/k versus H+ diagrrams."}
{"id": "PMID:13550", "title": "Light-dependent interactions of phenazine methosulfate with 3-(3,4-dichlorophenyl)-1,1-dimethylurea-poisoned chloroplasts.", "content": "The chlorophyll fluorescence of isolated chloroplasts in the presence of phenazine methosulfate (PMS) and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) can be quenched in a light-depentdent reaction. This phenomenan has been studied and the following observations were made: 1. Quenching occurs under non-phosphorylating conditions and is stimulated by Mg2+ ions. 2. Under the same conditions, a light-dependent, Mg2+ stimulated transient decrease of absorption at change and binding of PMS. Others, such as methylamine, ammonia, gramicidin and nigericin do not. It is suggested that fluorescence quenching, transient absorption change and binding of PMS are casually related. The concept, postulated by others, that a high-energy state of the chloroplast membrane is involved in the fluorescence lowering is questioned.", "contents": "Light-dependent interactions of phenazine methosulfate with 3-(3,4-dichlorophenyl)-1,1-dimethylurea-poisoned chloroplasts. The chlorophyll fluorescence of isolated chloroplasts in the presence of phenazine methosulfate (PMS) and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) can be quenched in a light-depentdent reaction. This phenomenan has been studied and the following observations were made: 1. Quenching occurs under non-phosphorylating conditions and is stimulated by Mg2+ ions. 2. Under the same conditions, a light-dependent, Mg2+ stimulated transient decrease of absorption at change and binding of PMS. Others, such as methylamine, ammonia, gramicidin and nigericin do not. It is suggested that fluorescence quenching, transient absorption change and binding of PMS are casually related. The concept, postulated by others, that a high-energy state of the chloroplast membrane is involved in the fluorescence lowering is questioned."}
{"id": "PMID:13588", "title": "Kinetics and properties of L-glutaminase and L-asparaginase activities of Pseudomonas ovalis.", "content": "Pseudomonas ovalis produces L-glutaminase and L-asparaginase activities simultaneously upon induction by L-glutamine or L-asparagin in the growth medium. Both activities are confined to the cell during active growth and are not released into the medium. The apparent Km values are 1.4 X 10(-2) M and 6 X 10(-3) M for L-glutamine and L-asparagine substrates, respectively. Induction of both activities is substantially favoured in media with initial pH values higher than 7. In buffered yeast extract L-asparagine medium, significant amounts of L-glutaminase and L-asparaginase activities appeared towards the end of the exponential phase and along the stationary phase. The process of enzyme formation showed a firm link to the cell active growth, as evidenced by the use of growth inhibitors.", "contents": "Kinetics and properties of L-glutaminase and L-asparaginase activities of Pseudomonas ovalis. Pseudomonas ovalis produces L-glutaminase and L-asparaginase activities simultaneously upon induction by L-glutamine or L-asparagin in the growth medium. Both activities are confined to the cell during active growth and are not released into the medium. The apparent Km values are 1.4 X 10(-2) M and 6 X 10(-3) M for L-glutamine and L-asparagine substrates, respectively. Induction of both activities is substantially favoured in media with initial pH values higher than 7. In buffered yeast extract L-asparagine medium, significant amounts of L-glutaminase and L-asparaginase activities appeared towards the end of the exponential phase and along the stationary phase. The process of enzyme formation showed a firm link to the cell active growth, as evidenced by the use of growth inhibitors."}
{"id": "PMID:13589", "title": "[Comparison in vitro between farm-yard manure and liquid manure (author's transl)].", "content": "Spreading of liquid manure in a grassland ecosystem, stable since a long time when treated with farm-yard manure, brings out a great unbalance in the soil. In comparison of farm-yard manure, the liquid manure involves -- a decrease of C and N in the soil, -- a deterioration of the soil structure, -- a dangerous change in the CEC for K+ and Na+, -- an excessive stimulation of the microflora. In brief, through its composition the liquid manure involves a hyperactivity of the microglora. This heterotropic microflora is particularly mineralizing and breaks down the organic matter. The result is a temporary increase in fertility. But this stimulation of the soil life disbalances the eco-system in which -- the pool of organic matter decreases without replacement, -- the content in Ca++ and Mg++ decreases to the benefit of K+ and Na+.", "contents": "[Comparison in vitro between farm-yard manure and liquid manure (author's transl)]. Spreading of liquid manure in a grassland ecosystem, stable since a long time when treated with farm-yard manure, brings out a great unbalance in the soil. In comparison of farm-yard manure, the liquid manure involves -- a decrease of C and N in the soil, -- a deterioration of the soil structure, -- a dangerous change in the CEC for K+ and Na+, -- an excessive stimulation of the microflora. In brief, through its composition the liquid manure involves a hyperactivity of the microglora. This heterotropic microflora is particularly mineralizing and breaks down the organic matter. The result is a temporary increase in fertility. But this stimulation of the soil life disbalances the eco-system in which -- the pool of organic matter decreases without replacement, -- the content in Ca++ and Mg++ decreases to the benefit of K+ and Na+."}
{"id": "PMID:13590", "title": "[Lymphogenic osteomyelitis of the foot (author's transl)].", "content": "The special way of infection of the lymphogenic osteomyelitis caused by trivial trauma is demonstrated in 4 cases. Germ ascension is done by lymphatics or fissures in the tissue, as it is well known in the panaritium ossale. The treatment consists in removing the focus of infection, irrigation-suction drainage and specific antibiotic therapy. Trivial trauma of the lower extremity should be treated according to the principles of asepsis.", "contents": "[Lymphogenic osteomyelitis of the foot (author's transl)]. The special way of infection of the lymphogenic osteomyelitis caused by trivial trauma is demonstrated in 4 cases. Germ ascension is done by lymphatics or fissures in the tissue, as it is well known in the panaritium ossale. The treatment consists in removing the focus of infection, irrigation-suction drainage and specific antibiotic therapy. Trivial trauma of the lower extremity should be treated according to the principles of asepsis."}
{"id": "PMID:13591", "title": "Effect of cholera enterotoxin preparations on cutaneous response in rabbit under varied conditions.", "content": "Enterotoxic activity of two preparations obtained from Vibrio cholerae, B-53-6 Inaba and B-53-10 Ogawa was tested in ligated ileal loops of rabbit. The biologically active enterotoxic preparations were further used to study the permeability reaction in rabbit skin. Cutaneous response tended to be linear only with higher concentrations of the toxin and showed maximum blueing intensity between 16 and 24 hrs of intracutaneous inoculation. Exposure of enterotoxin preparations to elevated temperatures greatly reduced the cutaneous response and the activity was completely lost at 100 degrees C. Change in pH towards alkaline side lowered the permeability activity to lesser extent as compared to a shift on acidic side. However, a residual activity could still be detected when pH of the enterotoxins was lowered to 3 at 30 degrees C for 4 hrs.", "contents": "Effect of cholera enterotoxin preparations on cutaneous response in rabbit under varied conditions. Enterotoxic activity of two preparations obtained from Vibrio cholerae, B-53-6 Inaba and B-53-10 Ogawa was tested in ligated ileal loops of rabbit. The biologically active enterotoxic preparations were further used to study the permeability reaction in rabbit skin. Cutaneous response tended to be linear only with higher concentrations of the toxin and showed maximum blueing intensity between 16 and 24 hrs of intracutaneous inoculation. Exposure of enterotoxin preparations to elevated temperatures greatly reduced the cutaneous response and the activity was completely lost at 100 degrees C. Change in pH towards alkaline side lowered the permeability activity to lesser extent as compared to a shift on acidic side. However, a residual activity could still be detected when pH of the enterotoxins was lowered to 3 at 30 degrees C for 4 hrs."}
{"id": "PMID:13594", "title": "Pyruvate metabolism in rat brain mitochondria.", "content": "1. Oxidation of pyruvate by rat brain mitochondria was stimulated in state 3 by malate or succinate up to 250 nmoles O2/mg protein/min. Oxidation of malate, succinate, 2-oxoglutarate or glutamate as the sole substrates, was 1/4 - 1/5 that observed with pyruvate. 2. Maximum oxygen consumption in state 3 was observed at pH 6.90 - 7.20, whereas in state 4 it was not affected by changes in pH. 3. In state 4, in the absence of exogenous acceptor or acetyl residues, acetate was the main oxidation product, corresponding to about 80% of the amount of pyruvate utilized. Malate did not affect the rate of pyruvate utilization but lowered acetate concentration and raised concentration of citrate and 2-oxoglutarate. 4. In state 3, pyruvate and malate were converted mainly to 2-oxoglutarate, its concentration being three times as high as that of citrate. 5. Formation of citrate, 2-oxoglutarate and acetate from pyruvate in brain is considered as a function of availability of the acceptor of acetyl residues and the energy state of mitochondrion.", "contents": "Pyruvate metabolism in rat brain mitochondria. 1. Oxidation of pyruvate by rat brain mitochondria was stimulated in state 3 by malate or succinate up to 250 nmoles O2/mg protein/min. Oxidation of malate, succinate, 2-oxoglutarate or glutamate as the sole substrates, was 1/4 - 1/5 that observed with pyruvate. 2. Maximum oxygen consumption in state 3 was observed at pH 6.90 - 7.20, whereas in state 4 it was not affected by changes in pH. 3. In state 4, in the absence of exogenous acceptor or acetyl residues, acetate was the main oxidation product, corresponding to about 80% of the amount of pyruvate utilized. Malate did not affect the rate of pyruvate utilization but lowered acetate concentration and raised concentration of citrate and 2-oxoglutarate. 4. In state 3, pyruvate and malate were converted mainly to 2-oxoglutarate, its concentration being three times as high as that of citrate. 5. Formation of citrate, 2-oxoglutarate and acetate from pyruvate in brain is considered as a function of availability of the acceptor of acetyl residues and the energy state of mitochondrion."}
{"id": "PMID:13595", "title": "Purification and properties of two protease inhibitors from rat skin inhibiting papain and other SH-proteases.", "content": "Two papain inhibitors, I1 and I2, from rat skin extract were purified by affinity chromatography on KSCN-modified papain-agarose gel and by gel filtration on Sephadex G-100. I1 had a molecular weight of 74 000, a pI of 4.6, and it contained 4% of carbohydrates. I1 inhibited papain, ficin, bromelain, rat skin benzoylarginine-2-naphthylamide hydrolase, and to a minor extent, rat skin cathepsin C and bovine trypsin. Bovine chymotrypsin or rat skin cathepsin D were not inhibited and benzoylarginine-2-naphthylamide hydrolase was inhibited only at alkaline pH. An inhibitor corresponding to I1 was present in various rat tissues and also in serum. A similar inhibitor was present in the skin of cat, rabbit, guinea pig, and man. I2 had a molecular weight of 13 400, a pI of 4.9 and it contained no carbohydrates. I2 inhibited all thiol proteases tested, but not trypsin, chymotrypsin, or rat skin cathepsin D. I2 formed an equimolar complex with papain and benzoylarginine-2-naphthylamide hydrolase. I2 was present in rat skin, muscle, lung, and small intestine, but not in kidney, liver, or serum. A similar inhibitor was found in skin extracts of cat, rabbit, guinea pig, and man.", "contents": "Purification and properties of two protease inhibitors from rat skin inhibiting papain and other SH-proteases. Two papain inhibitors, I1 and I2, from rat skin extract were purified by affinity chromatography on KSCN-modified papain-agarose gel and by gel filtration on Sephadex G-100. I1 had a molecular weight of 74 000, a pI of 4.6, and it contained 4% of carbohydrates. I1 inhibited papain, ficin, bromelain, rat skin benzoylarginine-2-naphthylamide hydrolase, and to a minor extent, rat skin cathepsin C and bovine trypsin. Bovine chymotrypsin or rat skin cathepsin D were not inhibited and benzoylarginine-2-naphthylamide hydrolase was inhibited only at alkaline pH. An inhibitor corresponding to I1 was present in various rat tissues and also in serum. A similar inhibitor was present in the skin of cat, rabbit, guinea pig, and man. I2 had a molecular weight of 13 400, a pI of 4.9 and it contained no carbohydrates. I2 inhibited all thiol proteases tested, but not trypsin, chymotrypsin, or rat skin cathepsin D. I2 formed an equimolar complex with papain and benzoylarginine-2-naphthylamide hydrolase. I2 was present in rat skin, muscle, lung, and small intestine, but not in kidney, liver, or serum. A similar inhibitor was found in skin extracts of cat, rabbit, guinea pig, and man."}
{"id": "PMID:13596", "title": "Histochemical studies on the mucins of the vertebrate tongues. VII. Histochemical analysis of mucosubstances in the tongues of some fishes.", "content": "The tongues of three fishes were investigated histochemically to determine the distribution and nature of mucosubstances by employing recent techniques and the results were considered comparatively with the lingual mucosubstances of other vertebrates. A heterogenous distribution of neutral mucosubstances, sulfomucins and sialomucins in various lingual sites was noted. The taste buds and/or free nerve endings were found to be restricted in the areas containing abundance of goblet cells. In non-gustatory areas of tongue, the goblet cells were very few or absent. Importance of lingual histology in establishing phylogenetic relationships and the possible functional significance of the mucosubstances in the physiology of gustation is discussed in detail.", "contents": "Histochemical studies on the mucins of the vertebrate tongues. VII. Histochemical analysis of mucosubstances in the tongues of some fishes. The tongues of three fishes were investigated histochemically to determine the distribution and nature of mucosubstances by employing recent techniques and the results were considered comparatively with the lingual mucosubstances of other vertebrates. A heterogenous distribution of neutral mucosubstances, sulfomucins and sialomucins in various lingual sites was noted. The taste buds and/or free nerve endings were found to be restricted in the areas containing abundance of goblet cells. In non-gustatory areas of tongue, the goblet cells were very few or absent. Importance of lingual histology in establishing phylogenetic relationships and the possible functional significance of the mucosubstances in the physiology of gustation is discussed in detail."}
{"id": "PMID:13597", "title": "Histochemistry of Centroorhynchus falconis (Das, 1950).", "content": "With a view to augment the understanding of the animal mucosubstances in general and Acanthocephalan mucosubstances in particular, Acanthocephalan worms of (Centrorhynchus falconis, Das, 1950) were investigated histochemically by employing recent techniques. Variations in the intensity of histochemical reactions in different tissues revealed a heterogenous distribution of mucosubstances. The cuticle contained a mixture of periodate reactive neutral mucosubstances and sulfomucins, whereas the subcuticle contained only glycogen. Retractor muscles contained glycogen together with some acidic mucosubstances which exhibited alcianophilia only at high pH. Cement glands elaborated a mixture of glycogen and galactogen. Histochemical methods revealed two types of acanthors: Some contained only glycogen, whereas others contained glycogen and galactogen.", "contents": "Histochemistry of Centroorhynchus falconis (Das, 1950). With a view to augment the understanding of the animal mucosubstances in general and Acanthocephalan mucosubstances in particular, Acanthocephalan worms of (Centrorhynchus falconis, Das, 1950) were investigated histochemically by employing recent techniques. Variations in the intensity of histochemical reactions in different tissues revealed a heterogenous distribution of mucosubstances. The cuticle contained a mixture of periodate reactive neutral mucosubstances and sulfomucins, whereas the subcuticle contained only glycogen. Retractor muscles contained glycogen together with some acidic mucosubstances which exhibited alcianophilia only at high pH. Cement glands elaborated a mixture of glycogen and galactogen. Histochemical methods revealed two types of acanthors: Some contained only glycogen, whereas others contained glycogen and galactogen."}
{"id": "PMID:13599", "title": "Intramuscular premedication with lorazepam.", "content": "Lorazepam is recognized as a tranquillizer. It is presented for intramuscular and intravenous injection. In a study of this drug's possible effects in premedication, its action was studied systematically when it was used for preoperative premedication. The drug has no side-effects other than drowsiness, which occurs in almost all cases. It produces very good premedication, sometimes with anterograde amnesia in the doses used. This anterograde amnesia is dependent on the dosage used but it is always accompanied by profound drowsiness, from which the patient can be roused verbally. The dose will be selected in relation to whether amnesia is desired or not. However, whatever the dose administered (over 2.5 mg), the tranquillizing effect is always of high quality.", "contents": "Intramuscular premedication with lorazepam. Lorazepam is recognized as a tranquillizer. It is presented for intramuscular and intravenous injection. In a study of this drug's possible effects in premedication, its action was studied systematically when it was used for preoperative premedication. The drug has no side-effects other than drowsiness, which occurs in almost all cases. It produces very good premedication, sometimes with anterograde amnesia in the doses used. This anterograde amnesia is dependent on the dosage used but it is always accompanied by profound drowsiness, from which the patient can be roused verbally. The dose will be selected in relation to whether amnesia is desired or not. However, whatever the dose administered (over 2.5 mg), the tranquillizing effect is always of high quality."}
{"id": "PMID:13600", "title": "The amnesic action of diazepam, flunitrazepam and lorazepam in man.", "content": "Studies in man show that it is possible to reliably study the incidence, degree and duration of amnesia produced by drugs by showing patients 10 postcards and testing their ability to recall or recognise them six hours later. Using this method of study it was found that 1 mg flunitrazepam produced a comparable degree of amnesia to 10 mg diazepam, although its action was slightly longer. This difference was more marked when double doses were studied. The onset of the amnesic action of both drugs occurred within 2 minutes of their intravenous injection and rarely persisted for more than 10-15 minutes. In contrast, with 4 mg lorazepam the onset of amnesia was slower and persisted for up to 270 minutes. This was accompanied by a moderate but not excessive amount of drowsiness. Possible clinical uses for such a drug deserve serious consideration.", "contents": "The amnesic action of diazepam, flunitrazepam and lorazepam in man. Studies in man show that it is possible to reliably study the incidence, degree and duration of amnesia produced by drugs by showing patients 10 postcards and testing their ability to recall or recognise them six hours later. Using this method of study it was found that 1 mg flunitrazepam produced a comparable degree of amnesia to 10 mg diazepam, although its action was slightly longer. This difference was more marked when double doses were studied. The onset of the amnesic action of both drugs occurred within 2 minutes of their intravenous injection and rarely persisted for more than 10-15 minutes. In contrast, with 4 mg lorazepam the onset of amnesia was slower and persisted for up to 270 minutes. This was accompanied by a moderate but not excessive amount of drowsiness. Possible clinical uses for such a drug deserve serious consideration."}
{"id": "PMID:13601", "title": "Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man.", "content": "The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs.", "contents": "Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man. The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs."}
{"id": "PMID:13602", "title": "Turku sugar studies XX. Microbiological findings and plaque index values in relation to 1-year use of xylitol chewing gum.", "content": "The aim was to study possible alterations in the microbial flora of plaque and saliva in relation to partial substitution of dietary sucrose with xylitol. The development of plaque index values was observed simultaneously. These observations were carried out during a 1-year clinical trial, the effects of sucrose (S) and xylitol (X) chewing gum on the incidence of dental caries being observed in 100 young adults. Paraffin-stimulated saliva samples were diluted stepwise and cultivated on Rogosa S.L. agar and Sabouraud agar aerobically. Lyophilized dental plaque samples were cultivated on phenol red agar under anaerobic and aerobic conditions. The pH-values were measured after incubating the mixed plaque flora for 1 and 7 days in the presence of various sugars. Both the arithmetic and geometric means of the total CFU values on Rogosa S.L. agar decreased in the S-group at the 6-month phase but returned to the starting level after one year, whereas in the X-group they decreased or remained on the starting level. At the 6-month phase the difference between the groups was significant (U-test, p = 0.0013) and almost significant (U-test, p = 0.0569) at the end of the study. No significant differences or changes could be seen between or within the groups on Sabouraud agar. The geometric mean values of S. sanguis and S. mutans as well as the total CFU values on phenol red agar decreased considerably in both the S- and X-groups, but no significant differences could be detected in any of the streptococcal counts between the groups. The pH of the carbohydrate-containing culture media infected with mixed dental plaque significantly decreased, with the exception of the xylitol containing ones in which the pH values were not lowered even after 7 days' incubation. A significant decrease in plaque formation in relation of chewing per se was demonstrable. The difference in the plaque index values equalling or exceeding 2 was significant between the S- and X-groups. No bacterial adaptation to utilize xylitol occurred during the trial.", "contents": "Turku sugar studies XX. Microbiological findings and plaque index values in relation to 1-year use of xylitol chewing gum. The aim was to study possible alterations in the microbial flora of plaque and saliva in relation to partial substitution of dietary sucrose with xylitol. The development of plaque index values was observed simultaneously. These observations were carried out during a 1-year clinical trial, the effects of sucrose (S) and xylitol (X) chewing gum on the incidence of dental caries being observed in 100 young adults. Paraffin-stimulated saliva samples were diluted stepwise and cultivated on Rogosa S.L. agar and Sabouraud agar aerobically. Lyophilized dental plaque samples were cultivated on phenol red agar under anaerobic and aerobic conditions. The pH-values were measured after incubating the mixed plaque flora for 1 and 7 days in the presence of various sugars. Both the arithmetic and geometric means of the total CFU values on Rogosa S.L. agar decreased in the S-group at the 6-month phase but returned to the starting level after one year, whereas in the X-group they decreased or remained on the starting level. At the 6-month phase the difference between the groups was significant (U-test, p = 0.0013) and almost significant (U-test, p = 0.0569) at the end of the study. No significant differences or changes could be seen between or within the groups on Sabouraud agar. The geometric mean values of S. sanguis and S. mutans as well as the total CFU values on phenol red agar decreased considerably in both the S- and X-groups, but no significant differences could be detected in any of the streptococcal counts between the groups. The pH of the carbohydrate-containing culture media infected with mixed dental plaque significantly decreased, with the exception of the xylitol containing ones in which the pH values were not lowered even after 7 days' incubation. A significant decrease in plaque formation in relation of chewing per se was demonstrable. The difference in the plaque index values equalling or exceeding 2 was significant between the S- and X-groups. No bacterial adaptation to utilize xylitol occurred during the trial."}
{"id": "PMID:13603", "title": "Turku sugar studies XXI. Xylitol, sorbitol-, fructose- and sucrose-induced physico-chemical changes in saliva.", "content": "The aim was to study eventual physico-chemical changes occurring in whole saliva due to sweetened and unsweetened stimulators. The assay was carried out in 10 female subjects with regard to changes of pH, buffering capacity and electrolytes in saliva as influenced by chewing of fructose, sucrose, sorbitol and xylitol gum, gum base and paraffin. The flow rate of saliva was measured in relation to use of xylitol and sucrose chewing gum and unsweetened gum base. These sweeteners increased significantly the salivary flow rate in comparison to the unsweetened gum base. Generally, xylitol and sorbitol on one hand, and sucrose and fructose on the other, behaved in an almost similar way. Increased buffering capacity and elevation of pH saliva was found in the presence of the polyols tested.", "contents": "Turku sugar studies XXI. Xylitol, sorbitol-, fructose- and sucrose-induced physico-chemical changes in saliva. The aim was to study eventual physico-chemical changes occurring in whole saliva due to sweetened and unsweetened stimulators. The assay was carried out in 10 female subjects with regard to changes of pH, buffering capacity and electrolytes in saliva as influenced by chewing of fructose, sucrose, sorbitol and xylitol gum, gum base and paraffin. The flow rate of saliva was measured in relation to use of xylitol and sucrose chewing gum and unsweetened gum base. These sweeteners increased significantly the salivary flow rate in comparison to the unsweetened gum base. Generally, xylitol and sorbitol on one hand, and sucrose and fructose on the other, behaved in an almost similar way. Increased buffering capacity and elevation of pH saliva was found in the presence of the polyols tested."}
{"id": "PMID:13604", "title": "Reduced inactivation of tyrosine aminotransferase in the prefused rat liver in the presence of ethanol.", "content": "The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally -- 4 hrs potentiates the effects induced by pimozide (0.04 mg/kg intraperitoneally -- 6 hrs) which preferentially blocks central dopamine (DA) receptors, but not the effects induced by phenoxybenzamine (0.5 mg/kg intraperitoneally -- 30 min.) which blocks central noradrenaline (NA) receptors. Furthermore, the behavioural suppression induced by chlorpromazine (0.5 mg/kg intraperitoneally -- 15 min.), thioridazine (1.5 mg/kg intraperitoneally -- 15 min.), or haloperidol (0.02 mg/kg intraperitoneally -- 15 min.) were not potentiated by the administration of the inhibitor of DA-beta-hydroxylase, bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63) 4 mg/kg subcutaneously -- 1 hr). The potentiation by alpha-MT of the clinical effects of antipsychotic drugs and of their behavioural effects in animal experiments is in all probability due to a blockade by alpha-MT of a feed-back mediated compensatory increase in the catecholamine synthesis as a result of a blockade of central NA and/or DA receptors by the antipsychotic drugs. Since, in the present experiments, the behavioural effects induced by drugs which block central DA but not NA receptors were potentiated by the simultaneous administration of alpha-MT, it seemed probable that the disruption of conditioned behaviours by antipsychotic drugs is due to a blockade of central DA receptors. In view of the fact that the ability to selectively disrupt conditioned behaviours is shared by a wide range of antipsychotic drugs differing in chemical structure and also in their mode of action, it is possible that a blockade of DA neurotransmission is also of primary importance for the clinical effects induced by antipsychotic drugs.", "contents": "Reduced inactivation of tyrosine aminotransferase in the prefused rat liver in the presence of ethanol. The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally -- 4 hrs potentiates the effects induced by pimozide (0.04 mg/kg intraperitoneally -- 6 hrs) which preferentially blocks central dopamine (DA) receptors, but not the effects induced by phenoxybenzamine (0.5 mg/kg intraperitoneally -- 30 min.) which blocks central noradrenaline (NA) receptors. Furthermore, the behavioural suppression induced by chlorpromazine (0.5 mg/kg intraperitoneally -- 15 min.), thioridazine (1.5 mg/kg intraperitoneally -- 15 min.), or haloperidol (0.02 mg/kg intraperitoneally -- 15 min.) were not potentiated by the administration of the inhibitor of DA-beta-hydroxylase, bis-(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63) 4 mg/kg subcutaneously -- 1 hr). The potentiation by alpha-MT of the clinical effects of antipsychotic drugs and of their behavioural effects in animal experiments is in all probability due to a blockade by alpha-MT of a feed-back mediated compensatory increase in the catecholamine synthesis as a result of a blockade of central NA and/or DA receptors by the antipsychotic drugs. Since, in the present experiments, the behavioural effects induced by drugs which block central DA but not NA receptors were potentiated by the simultaneous administration of alpha-MT, it seemed probable that the disruption of conditioned behaviours by antipsychotic drugs is due to a blockade of central DA receptors. In view of the fact that the ability to selectively disrupt conditioned behaviours is shared by a wide range of antipsychotic drugs differing in chemical structure and also in their mode of action, it is possible that a blockade of DA neurotransmission is also of primary importance for the clinical effects induced by antipsychotic drugs."}
{"id": "PMID:13605", "title": "Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs.", "content": "The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function.", "contents": "Potentiation by alpha-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs. The mode of action whereby alpha-methyltyrosine (alpha-MT) potentiates the behavioural effects induced by catecholamine receptor blocking antipsychotic drugs was investigated in rats trained to lever-press for food on a fixed-ratio 40 schedule of reinforcement. It was found that alpha-MT (20 mg/kg intraperitoneally - 4 hrs potentiates the effects induced by pimace, causing an alteration of the neuronal function."}
{"id": "PMID:13606", "title": "Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat.", "content": "The corpus-fundus of the urinary bladder of man and cat was studied in vitro with respect to type of beta-adrenergic receptors. In both species beta-adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1-receptors were found. In the human bladder the beta-receptors had neither beta1- nor beta2-characteristics. It is suggested that the beta-adrenergic receptors in the corpus-fundus of the human bladder are of a third type.", "contents": "Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat. The corpus-fundus of the urinary bladder of man and cat was studied in vitro with respect to type of beta-adrenergic receptors. In both species beta-adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1-receptors were found. In the human bladder the beta-receptors had neither beta1- nor beta2-characteristics. It is suggested that the beta-adrenergic receptors in the corpus-fundus of the human bladder are of a third type."}
{"id": "PMID:13607", "title": "Cholinergic mechanisms in the learning and memory facilitating effect of caffeine.", "content": "Experiments are made to train rats in a maze involving memory tests 24 hours and 14 days after training. As it was established in previous studies of the authors, caffeine introduced in low doses (5 mg/kg) 5 min before training facilitates learning and memory. Applied immediately after training, caffeine even in higher doses (20 mg/kg) also improves the memory indices 24 hours and 14 days after the experiment. The anticholinergic agents spasmolytine and scopolamine in higher doses (20 and 2 mg/kg respectively) have a markedly deteriorating effect on learning, while scopolamine deteriorates retention as well. Introduced after training, both drugs deteriorate memory even in smaller doses - 2 and 0,25 mg/kg, respectively. On the background of the anticholinergic agents (especially in the higher doses), the learning and memory facilitating effects of caffeine are not manifested in any of the experimental setups (administration before and after train. The results obtained show that cholinergic mechanisms play an important role in the learning and memory facilitating effect of caffeine. A necessary condition for the manifestation of this effect is the optimum functional level of these cholinergic mechanisms in the central nervous system.", "contents": "Cholinergic mechanisms in the learning and memory facilitating effect of caffeine. Experiments are made to train rats in a maze involving memory tests 24 hours and 14 days after training. As it was established in previous studies of the authors, caffeine introduced in low doses (5 mg/kg) 5 min before training facilitates learning and memory. Applied immediately after training, caffeine even in higher doses (20 mg/kg) also improves the memory indices 24 hours and 14 days after the experiment. The anticholinergic agents spasmolytine and scopolamine in higher doses (20 and 2 mg/kg respectively) have a markedly deteriorating effect on learning, while scopolamine deteriorates retention as well. Introduced after training, both drugs deteriorate memory even in smaller doses - 2 and 0,25 mg/kg, respectively. On the background of the anticholinergic agents (especially in the higher doses), the learning and memory facilitating effects of caffeine are not manifested in any of the experimental setups (administration before and after train. The results obtained show that cholinergic mechanisms play an important role in the learning and memory facilitating effect of caffeine. A necessary condition for the manifestation of this effect is the optimum functional level of these cholinergic mechanisms in the central nervous system."}
{"id": "PMID:13609", "title": "Amylase, hepatic enzymes and bilirubin in serum of chronic alcoholics.", "content": "The serum concentration of bilirubin and the activities of aspartate aminotransferase (ASAT, GOT), alanine aminotransferase (ALAT, GPT), gamma-glutamyltransferase (GT), total amylase and pancreatic isoamylase have been determined in serum of 182 male chronic alcoholics. Twelve per cent had abnormally high levels of bilirubin, 73% increased activity of S-ASAT, 50% increased S-ALAT, and 69% increased S-GT. The highest values were often found after 5-20 years of well documented alcoholism. Some patients with alcoholism of more than 20 years' duration displayed a slight tendency towards normalization of the activities. For all parameters the scatter around the mean was greater in the patients than in the controls. Patients who had had attacks of delirium showed slightly higher S-ASAT and S-ALAT than other alcoholics. Determination of S-ALAT and S-bilirubin did not add to the cases with abnormal laboratory tests demonstrated by the combination of S-ASAT and S-GT. In 14 patients the above mentioned parameters were within normal limits, even though severe alcoholism had lasted for many years. Isoamylase determination disclosed 20% to have decreased activity of pancreatic isoamylases in serum, whereas only 6% had low total serum amylase activity.", "contents": "Amylase, hepatic enzymes and bilirubin in serum of chronic alcoholics. The serum concentration of bilirubin and the activities of aspartate aminotransferase (ASAT, GOT), alanine aminotransferase (ALAT, GPT), gamma-glutamyltransferase (GT), total amylase and pancreatic isoamylase have been determined in serum of 182 male chronic alcoholics. Twelve per cent had abnormally high levels of bilirubin, 73% increased activity of S-ASAT, 50% increased S-ALAT, and 69% increased S-GT. The highest values were often found after 5-20 years of well documented alcoholism. Some patients with alcoholism of more than 20 years' duration displayed a slight tendency towards normalization of the activities. For all parameters the scatter around the mean was greater in the patients than in the controls. Patients who had had attacks of delirium showed slightly higher S-ASAT and S-ALAT than other alcoholics. Determination of S-ALAT and S-bilirubin did not add to the cases with abnormal laboratory tests demonstrated by the combination of S-ASAT and S-GT. In 14 patients the above mentioned parameters were within normal limits, even though severe alcoholism had lasted for many years. Isoamylase determination disclosed 20% to have decreased activity of pancreatic isoamylases in serum, whereas only 6% had low total serum amylase activity."}
{"id": "PMID:13613", "title": "Oxygen transport and hemodynamics of stroma-free hemoglobin solutions.", "content": "The intravascular persistence of hb-W is significantly longer than of pyridoxylated hb (hb-PLP), however, no significant differences in BV were observed after isovolemic exchange of 20 ml/kg b.w. Even though the oxygen affinity of hb-PLP in vitro was reduced when compared to the affinity of hb-W significant differences in vivo were lacking. The development of hypovolemia and thus the lack of an adequate increase in cardiac output have been recognized as the most relevant causes to explain the changes observed. Neither of the solutions is yet to be recommended for clinical blood replacement therapy.", "contents": "Oxygen transport and hemodynamics of stroma-free hemoglobin solutions. The intravascular persistence of hb-W is significantly longer than of pyridoxylated hb (hb-PLP), however, no significant differences in BV were observed after isovolemic exchange of 20 ml/kg b.w. Even though the oxygen affinity of hb-PLP in vitro was reduced when compared to the affinity of hb-W significant differences in vivo were lacking. The development of hypovolemia and thus the lack of an adequate increase in cardiac output have been recognized as the most relevant causes to explain the changes observed. Neither of the solutions is yet to be recommended for clinical blood replacement therapy."}
{"id": "PMID:13615", "title": "Problems in determination of oxygen dissociation of avian blood.", "content": "No appreciable errors are expected in determination of blood gas values and pH using classical techniques provided time of anaerobic storage is kept small and is, if unavoidable performed on ice. In particular, dissociation curves may safely be analyzed with the Van Slyke technique which is in disagreement with the conclusions of Lutz et al. (1973). For measurement of PO2 and PCO2, delay time is mainly dictated by response time of the electrodes; measurements may have to be corrected for metabolism, particularly in high PO2 range.", "contents": "Problems in determination of oxygen dissociation of avian blood. No appreciable errors are expected in determination of blood gas values and pH using classical techniques provided time of anaerobic storage is kept small and is, if unavoidable performed on ice. In particular, dissociation curves may safely be analyzed with the Van Slyke technique which is in disagreement with the conclusions of Lutz et al. (1973). For measurement of PO2 and PCO2, delay time is mainly dictated by response time of the electrodes; measurements may have to be corrected for metabolism, particularly in high PO2 range."}
{"id": "PMID:13616", "title": "A theoretical model of the respiratory function of blood.", "content": "The model of the respiratory function of blood as outlined here is judged to be a powerful tool for the evaluation of the potential effects of changes in blood as well as tissue parameters upon the supply of oxygen to tissue. The erythrocyte-plasma disequilibria in lung and systemic capillaries which is a consequence of the slowness of plasma CO2 hydrolysis are not significant in terms of the delivery of oxygen to tissue, but result in slightly lower unloading of CO2 in the lungs compared to that which might occur at full equilibration. However, the effects might be of greater interest when relating pH values measured by in vivo sampling to actual values prevailing within the capillaries. The physiological importances of hyperventilation and elevated DPG levels in anemia cannot as yet be clarified. If anything, it appears that increased DPG is a compensatory mechanism to restore proper O2-Hb affinity in alkalosis, while the purpose for an alkalosis is not obvious.", "contents": "A theoretical model of the respiratory function of blood. The model of the respiratory function of blood as outlined here is judged to be a powerful tool for the evaluation of the potential effects of changes in blood as well as tissue parameters upon the supply of oxygen to tissue. The erythrocyte-plasma disequilibria in lung and systemic capillaries which is a consequence of the slowness of plasma CO2 hydrolysis are not significant in terms of the delivery of oxygen to tissue, but result in slightly lower unloading of CO2 in the lungs compared to that which might occur at full equilibration. However, the effects might be of greater interest when relating pH values measured by in vivo sampling to actual values prevailing within the capillaries. The physiological importances of hyperventilation and elevated DPG levels in anemia cannot as yet be clarified. If anything, it appears that increased DPG is a compensatory mechanism to restore proper O2-Hb affinity in alkalosis, while the purpose for an alkalosis is not obvious."}
{"id": "PMID:13627", "title": "Control of prolactin secretion by the hypothalamic catecholamines.", "content": "The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion.", "contents": "Control of prolactin secretion by the hypothalamic catecholamines. The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion."}
{"id": "PMID:13630", "title": "[Immunologic relations between cattle and ticks, specifically between cattle and Boophilus microplus].", "content": "In the present investigation, it has been demonstrated that cattle become resistant to ticks after several heavy infestations, particularly with B. microplus. During development of the infestations, antibodies against salivary glands of B. microplus were detected using 2 techniques: indirect immunofluorescence and immunoelectrophoresis. There is a positive causal relationship between antibody titer and resistance development. Two precipitating systems against B. microplus in infested cattle and 7 systems in immunized rabbits were studied. The systems 1 and 2 are similar in cattle and rabbits, but system 2 does not show any specificity, as it has been detected in cattle completely lacking tick infestations. Two one-day calves were treated with the antigen of B. microplus by injection of salivary glands and repeated infestations with a small number of larvae. They developed a pronounced resistance to the usual subsequent infestations by the ticks of the same species. Specific antibodies were found before the first usual infestation. This suggests that they might be responsible for resistance.", "contents": "[Immunologic relations between cattle and ticks, specifically between cattle and Boophilus microplus]. In the present investigation, it has been demonstrated that cattle become resistant to ticks after several heavy infestations, particularly with B. microplus. During development of the infestations, antibodies against salivary glands of B. microplus were detected using 2 techniques: indirect immunofluorescence and immunoelectrophoresis. There is a positive causal relationship between antibody titer and resistance development. Two precipitating systems against B. microplus in infested cattle and 7 systems in immunized rabbits were studied. The systems 1 and 2 are similar in cattle and rabbits, but system 2 does not show any specificity, as it has been detected in cattle completely lacking tick infestations. Two one-day calves were treated with the antigen of B. microplus by injection of salivary glands and repeated infestations with a small number of larvae. They developed a pronounced resistance to the usual subsequent infestations by the ticks of the same species. Specific antibodies were found before the first usual infestation. This suggests that they might be responsible for resistance."}
{"id": "PMID:13631", "title": "The occurrence of an intraerythrocytic microorganism Neitziella rezendei gen. nov. sp. nov. (Microtatobiotes, Rickettsiales) of poultry in Brazil.", "content": "An extremely polymorphous intraerythrocytic microorganism occurring in naturally infected turkeys, ducks and fowls has been discovered in the states of Minas Gerais, Rio de Janeiro and Espirito Santo. 2. Studies on the morphology and biology have shown that it is a hitherto undescribed heteroxenous parasite for which the name Neitziella rezendei gen. nov., sp. nov. is proposed. 3. Its morphological features permit its inclusion in the class Microtatobiotes and order Rickettsiales. 4. Microscopical examination of blood films have shown that the parasitic carrier state in turkeys persists for more than 200 days (endpoint not determined). 5. The natural mode of transmission needs to be determined. 6. The suspicion that the parasite may cause illthrift and deaths in poultry requires confirmation.", "contents": "The occurrence of an intraerythrocytic microorganism Neitziella rezendei gen. nov. sp. nov. (Microtatobiotes, Rickettsiales) of poultry in Brazil. An extremely polymorphous intraerythrocytic microorganism occurring in naturally infected turkeys, ducks and fowls has been discovered in the states of Minas Gerais, Rio de Janeiro and Espirito Santo. 2. Studies on the morphology and biology have shown that it is a hitherto undescribed heteroxenous parasite for which the name Neitziella rezendei gen. nov., sp. nov. is proposed. 3. Its morphological features permit its inclusion in the class Microtatobiotes and order Rickettsiales. 4. Microscopical examination of blood films have shown that the parasitic carrier state in turkeys persists for more than 200 days (endpoint not determined). 5. The natural mode of transmission needs to be determined. 6. The suspicion that the parasite may cause illthrift and deaths in poultry requires confirmation."}
{"id": "PMID:13632", "title": "Protease activity in female Ornithodoros tholozani ticks.", "content": "The protease activity in guts of Ornithodoros tholozani females was studied in vitro. The intracellular protease in Ornithodoros tholozani guts has a pH optimum of about 3.0. Hemoglobin is the preferred substrate, and bovine serum albumin is digested very slowly. In this respect the protease resembles cathepsin D. Unfed ticks contain a small amount of protease in the gut. After feeding the level of protease increases gradually for several days until peak protease activity is attained. The level of gut protease activity depends on the size of the blood meal taken and on the interval after feeding. After a period of peak protease activity, the level of protease declines. The level of gut protease in unmated females (kept at 27 degrees C) did not reach prefeeding levels within 100 days. The level of gut proteolytic activity, as determined by in vitro protease assays, does not reflect the degree of blood digestion which takes place in vivo. After a period of rapid digestion, lasting for about two weeks, the undigested part of the blood meal remains unchanged in the lumen of the gut. At that time the gut tissue contains considerable levels of protease, which can be demonstrated by in vitro assays. Presumably, the protease remains active inside the gut cells, although the uptake of hemoglobin from the gut lumen has ceased. The results are compared to those obtained in other tick species.", "contents": "Protease activity in female Ornithodoros tholozani ticks. The protease activity in guts of Ornithodoros tholozani females was studied in vitro. The intracellular protease in Ornithodoros tholozani guts has a pH optimum of about 3.0. Hemoglobin is the preferred substrate, and bovine serum albumin is digested very slowly. In this respect the protease resembles cathepsin D. Unfed ticks contain a small amount of protease in the gut. After feeding the level of protease increases gradually for several days until peak protease activity is attained. The level of gut protease activity depends on the size of the blood meal taken and on the interval after feeding. After a period of peak protease activity, the level of protease declines. The level of gut protease in unmated females (kept at 27 degrees C) did not reach prefeeding levels within 100 days. The level of gut proteolytic activity, as determined by in vitro protease assays, does not reflect the degree of blood digestion which takes place in vivo. After a period of rapid digestion, lasting for about two weeks, the undigested part of the blood meal remains unchanged in the lumen of the gut. At that time the gut tissue contains considerable levels of protease, which can be demonstrated by in vitro assays. Presumably, the protease remains active inside the gut cells, although the uptake of hemoglobin from the gut lumen has ceased. The results are compared to those obtained in other tick species."}
{"id": "PMID:13637", "title": "Human sleeping sickness in the Gboko endemic area of Nigeria.", "content": "Human infection with Trypanosoma gambiense in the Gboko endemic area was first reported in May, 1974 although T. gambiense sleeping sickness had been present there since the turn of the century. The disease is associated with the presence of the tsetse Glossina tachinoides and Glossina palpalis which is plentiful and widespread throughout the division as well as in thickets along the streams in the area. No successful attempt has been made to control the tsetse vector in the Division. The incidence and geographical distribution of cases of T. gambiense sleeping sickness in the Gboko area are described in this report. Cases were treated with Antrypol Tryparsamide mixture and Mel B. The highest number of cases of infection is usually picked up just before the start of the rains in early April. It is suggested that, for meaningful control of the disease a quick method should be devised to rid the area of the insect vector.", "contents": "Human sleeping sickness in the Gboko endemic area of Nigeria. Human infection with Trypanosoma gambiense in the Gboko endemic area was first reported in May, 1974 although T. gambiense sleeping sickness had been present there since the turn of the century. The disease is associated with the presence of the tsetse Glossina tachinoides and Glossina palpalis which is plentiful and widespread throughout the division as well as in thickets along the streams in the area. No successful attempt has been made to control the tsetse vector in the Division. The incidence and geographical distribution of cases of T. gambiense sleeping sickness in the Gboko area are described in this report. Cases were treated with Antrypol Tryparsamide mixture and Mel B. The highest number of cases of infection is usually picked up just before the start of the rains in early April. It is suggested that, for meaningful control of the disease a quick method should be devised to rid the area of the insect vector."}
{"id": "PMID:13638", "title": "Mel B toxicity in human trypanosomiasis in the Gboko endemic area of Nigeria.", "content": "Nine cases of Mel B (a melaminyl arsenical used in treating sleeping sickness patients who have developed central nervous system involvement) treated patients who developed reactions to the drug are described. They all developed high temperatures, pyrexia, diarrhoea, vomitting or itching and some had convulsions. Three of the nine described patients died. It is recommended that extra care and caution is needed while treating patients with Mel B.", "contents": "Mel B toxicity in human trypanosomiasis in the Gboko endemic area of Nigeria. Nine cases of Mel B (a melaminyl arsenical used in treating sleeping sickness patients who have developed central nervous system involvement) treated patients who developed reactions to the drug are described. They all developed high temperatures, pyrexia, diarrhoea, vomitting or itching and some had convulsions. Three of the nine described patients died. It is recommended that extra care and caution is needed while treating patients with Mel B."}
{"id": "PMID:13639", "title": "Principles of complementation interaction of ts mutants of orthomyxoviruses.", "content": "The possibility of complementation between ts mutants of fowl plague virus (FPV) belonging to 5 different complementation groups was studied using various time intervals between inoculation of the cells with two complementation partners. The structural proteins of virions formed on complementation of individual ts mutants with wild virus were analysed by polyacrylamide gel electrophoresis after amino acid pulse label followed by pulse chase. The features of complementation interactions between the mutants are discussed.", "contents": "Principles of complementation interaction of ts mutants of orthomyxoviruses. The possibility of complementation between ts mutants of fowl plague virus (FPV) belonging to 5 different complementation groups was studied using various time intervals between inoculation of the cells with two complementation partners. The structural proteins of virions formed on complementation of individual ts mutants with wild virus were analysed by polyacrylamide gel electrophoresis after amino acid pulse label followed by pulse chase. The features of complementation interactions between the mutants are discussed."}
{"id": "PMID:13640", "title": "Influence of host cell type on the density of herpes simplex virus particles.", "content": "The densities of purified herpes simplex virus (HSV) particles prepared from infected rabbit lung (ZP) and baby hamster kidney (BHK-21) cells were investigated in potassium tartrate (PT) and potassium citrate (PC) density gradients. Virions obtained from ZP cells exhibited a higher density than those from BHK-21 cells. In PT and PC gradients, the former banded at densities of 1.226 and 1.267, while tha latter at 1.194 and 1.233, respectively. Deenveloped viral particles prepared by Nonidet P-40 treatment from purified virions of either origin were found in PT and PC gradients at the densities of 1.263 and 1.320, respectively. The possible causes of the density change of virions propagated in different hosts are discussed.", "contents": "Influence of host cell type on the density of herpes simplex virus particles. The densities of purified herpes simplex virus (HSV) particles prepared from infected rabbit lung (ZP) and baby hamster kidney (BHK-21) cells were investigated in potassium tartrate (PT) and potassium citrate (PC) density gradients. Virions obtained from ZP cells exhibited a higher density than those from BHK-21 cells. In PT and PC gradients, the former banded at densities of 1.226 and 1.267, while tha latter at 1.194 and 1.233, respectively. Deenveloped viral particles prepared by Nonidet P-40 treatment from purified virions of either origin were found in PT and PC gradients at the densities of 1.263 and 1.320, respectively. The possible causes of the density change of virions propagated in different hosts are discussed."}
{"id": "PMID:13641", "title": "Reversible inhibition of interferon-induced antiviral state by deoxyadenosine.", "content": "Deoxyadenosine reversibly inhibited the development of antiviral state (AVS) in chick embryo fibroblasts stimulated by interferon. Studies on cellular macromolecular syntheses in deoxyadenosine-treated cells suggested that the inhibition was related to nucleolar RNA synthesis. Reference experiments with actinomycin D and cordycepin (3'deoxyadenosine) also implied causal- or interrelation between AVS development and nucleolar RNA synthesis.", "contents": "Reversible inhibition of interferon-induced antiviral state by deoxyadenosine. Deoxyadenosine reversibly inhibited the development of antiviral state (AVS) in chick embryo fibroblasts stimulated by interferon. Studies on cellular macromolecular syntheses in deoxyadenosine-treated cells suggested that the inhibition was related to nucleolar RNA synthesis. Reference experiments with actinomycin D and cordycepin (3'deoxyadenosine) also implied causal- or interrelation between AVS development and nucleolar RNA synthesis."}
{"id": "PMID:13642", "title": "Study of the priming effect of interferon in L cells. I. The primed interferon response and the kinetics of development of priming.", "content": "Interferon was detected one hour earlier, its production followed an enhanced pattern and became resistant to actinomycin D 30 minutes sooner in cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid than in unprimed cultures. The kinetics of development of the primed state was found to be a time and dose dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state.", "contents": "Study of the priming effect of interferon in L cells. I. The primed interferon response and the kinetics of development of priming. Interferon was detected one hour earlier, its production followed an enhanced pattern and became resistant to actinomycin D 30 minutes sooner in cultures primed by interferon pretreatment before stimulation by polyriboinosinic-polyribocytidylic acid than in unprimed cultures. The kinetics of development of the primed state was found to be a time and dose dependent phenomenon. The continuous presence of interferon during the pretreatment period was not required for the development of the primed state."}
{"id": "PMID:13643", "title": "Phenothiazine-induced alterations of immune response in experimental tick-borne encephalitis: morphological model analysis of events.", "content": "The depressive effect of trifluoperazine (TFP), a phenothiazine derivative, on the morphology of the development of immune response (IR) (humoral and cell-mediated component) was studied in mice given tick-borne encephalitis (TBE) virus, sheep red blood cells (SRBC) or the BCG vaccine. This effect was manifested by a decrease in the mitotic activity of lymphocytes and in the number of blastic transformations after antigenic stimulation. In virus-infected and TFP-given mice, lowered levels of specific virus neutralizing antibody (VNA), together with a pronounced reduction of the inflammatory response in the brain were found. No signs of cytotoxicity following administration of the drug were observed. The mechanism of the immunodepressive action of TFP are discussed.", "contents": "Phenothiazine-induced alterations of immune response in experimental tick-borne encephalitis: morphological model analysis of events. The depressive effect of trifluoperazine (TFP), a phenothiazine derivative, on the morphology of the development of immune response (IR) (humoral and cell-mediated component) was studied in mice given tick-borne encephalitis (TBE) virus, sheep red blood cells (SRBC) or the BCG vaccine. This effect was manifested by a decrease in the mitotic activity of lymphocytes and in the number of blastic transformations after antigenic stimulation. In virus-infected and TFP-given mice, lowered levels of specific virus neutralizing antibody (VNA), together with a pronounced reduction of the inflammatory response in the brain were found. No signs of cytotoxicity following administration of the drug were observed. The mechanism of the immunodepressive action of TFP are discussed."}
{"id": "PMID:13644", "title": "Influence of temperatures corresponding to those of the host animals on Tahyna virus.", "content": "The influence of temperature of 36.5 and 39.2 degrees C on uncloned low passage Tahyna virus in chick embryo cell cultures was studied in the course of 10 passages. At a high multiplicity of infection, the virus titres showed a considerable variability, especially at 39.2 degrees C. The cytopathic effect (CPE) apparent at both temperatures started later and was of lower intensity at 39.2 degrees C than at 36.5 degrees C. The temperature of 39.2 degrees C intensified the thermostable character of the virus. Changes in plaque size and virulence were connected mainly with the cultivation substrate of the virus.", "contents": "Influence of temperatures corresponding to those of the host animals on Tahyna virus. The influence of temperature of 36.5 and 39.2 degrees C on uncloned low passage Tahyna virus in chick embryo cell cultures was studied in the course of 10 passages. At a high multiplicity of infection, the virus titres showed a considerable variability, especially at 39.2 degrees C. The cytopathic effect (CPE) apparent at both temperatures started later and was of lower intensity at 39.2 degrees C than at 36.5 degrees C. The temperature of 39.2 degrees C intensified the thermostable character of the virus. Changes in plaque size and virulence were connected mainly with the cultivation substrate of the virus."}
{"id": "PMID:13645", "title": "Influence of temperature corresponding to that of the vector on Tahyna virus.", "content": "The behaviour of uncloned, low-passage Tahyna virus in an Aedes albopictus (AA) cell line at 28 and 20 degrees C was studied in the course of 10 passages. The virus multiplied at both temperatures without any apparent effect on the host cell. At 28 and 20 degrees C reduction of plaque size, decrease of peripheral virulence and weakening of thermostability were observed. Differences between both temperatures were only in the intensity of these changes.", "contents": "Influence of temperature corresponding to that of the vector on Tahyna virus. The behaviour of uncloned, low-passage Tahyna virus in an Aedes albopictus (AA) cell line at 28 and 20 degrees C was studied in the course of 10 passages. The virus multiplied at both temperatures without any apparent effect on the host cell. At 28 and 20 degrees C reduction of plaque size, decrease of peripheral virulence and weakening of thermostability were observed. Differences between both temperatures were only in the intensity of these changes."}
{"id": "PMID:13646", "title": "Cultivation of Lednice (Yaba 1) virus in goose, duck, and chick embryo cells.", "content": "Lednice (Yaba 1) virus was found to multiply in primary cultures of goose, duck and chick embryo cells. The size of inoculum and age of embryos used for preparation of primary cultures was decisive for the amount of multiplied virus. One strain (110) of Lednice virus showed reduced ability to induce a cytopathic effect in the first passage in chick embryo cells. Virus multiplication in all three kinds of cells was confirmed by immunofluorescence.", "contents": "Cultivation of Lednice (Yaba 1) virus in goose, duck, and chick embryo cells. Lednice (Yaba 1) virus was found to multiply in primary cultures of goose, duck and chick embryo cells. The size of inoculum and age of embryos used for preparation of primary cultures was decisive for the amount of multiplied virus. One strain (110) of Lednice virus showed reduced ability to induce a cytopathic effect in the first passage in chick embryo cells. Virus multiplication in all three kinds of cells was confirmed by immunofluorescence."}
{"id": "PMID:13648", "title": "Systematic management of the anxious patient.", "content": "The patient usually consults his family physician because of the physical symptoms of anxiety, usually cardiorespiratory, but often gastrointestinal or musculoskeletal. An organized, systematic approach includes these steps: an invitation to talk; identifying the problem; understanding the patient's wishes; choosing an appropriate drug (if necessary); involving the family, and behavioral modification techniques.", "contents": "Systematic management of the anxious patient. The patient usually consults his family physician because of the physical symptoms of anxiety, usually cardiorespiratory, but often gastrointestinal or musculoskeletal. An organized, systematic approach includes these steps: an invitation to talk; identifying the problem; understanding the patient's wishes; choosing an appropriate drug (if necessary); involving the family, and behavioral modification techniques."}
{"id": "PMID:13650", "title": "Observations of plasma secretin levels by radioimmunoassay in response to duodenal acidification and to a meat meal in humans.", "content": "The endogenous release of secretin in healthy human subjects was studied by measuring plasma secretin levels by radioimmunoassay (RIA) before, during, and following duodenal acidification and eating a meal. The sensitivity of our RIA was assessed by measuring plasma secretin levels during constant intravenous infusions of 4 graded doses of secretin. Our RIA detected significant increases (P less than 0.001) in plasma secretin with each dose, including a low dose of 0.125 U (41.3 ng)/kg hr. Intraduodenal infusion of 0.1 N HCl resulted in marked increases (P less than 0.001) in plasma secretin levels whenever pH in the second portion of the duodenum was reduced to less than 3.5. In contrast, following a meal, pH in the second portion of the duodenum remained consistently greater than 4.5 and plasma secretin levels showed no changes from basal levels. These studies confirm that endogenous release of secretin depends on an acidic pH of the duodenum, and insigificant changes in the plasma secretin level following ingestion of a meal suggest that endogenous release of secretin in the postprandial period is probably to small in quantity to be detected by the present radioimmunoassay method.", "contents": "Observations of plasma secretin levels by radioimmunoassay in response to duodenal acidification and to a meat meal in humans. The endogenous release of secretin in healthy human subjects was studied by measuring plasma secretin levels by radioimmunoassay (RIA) before, during, and following duodenal acidification and eating a meal. The sensitivity of our RIA was assessed by measuring plasma secretin levels during constant intravenous infusions of 4 graded doses of secretin. Our RIA detected significant increases (P less than 0.001) in plasma secretin with each dose, including a low dose of 0.125 U (41.3 ng)/kg hr. Intraduodenal infusion of 0.1 N HCl resulted in marked increases (P less than 0.001) in plasma secretin levels whenever pH in the second portion of the duodenum was reduced to less than 3.5. In contrast, following a meal, pH in the second portion of the duodenum remained consistently greater than 4.5 and plasma secretin levels showed no changes from basal levels. These studies confirm that endogenous release of secretin depends on an acidic pH of the duodenum, and insigificant changes in the plasma secretin level following ingestion of a meal suggest that endogenous release of secretin in the postprandial period is probably to small in quantity to be detected by the present radioimmunoassay method."}
{"id": "PMID:13651", "title": "Lower esophageal sphincter pressure and serum motilin levels.", "content": "The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release.", "contents": "Lower esophageal sphincter pressure and serum motilin levels. The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release."}
{"id": "PMID:13647", "title": "Imminent shock; a useful diagnosis in drug pathology.", "content": "A research has been carried out on a total of 121 persons with survival post-drug shock (DS), which registered 192 DS. Mention should be made of their predominance in the feminine sex (85 per cent) and their maximum frequency between the ages of 21-50 (average age 34). DS was the first adverse reaction to drugs in 71 per cent of the cases. Therefore DS unpredictability is very frequent. A retrospective study suggested the role of risk factors which should help the doctor to prevent DS (personal allergic antecedents, antecedents of adverse reactions to drugs, neuroses, disorders of endocrine glands, feminine sex, etc.). In 1970, the clinical concept of shock imminence (SI) was formulated and it is applied to various etiologies (drugs, insect stings, food). The existence of SI was identified in the case history of 14 per cent of the persons with DS. SI is a syndrome which includes all clinical manifestations with imminent potential of transformation into shock condition, and represents the stage precursory to the setting up of shock. The utility of SI diagnosis is maximum if it also includes the causal factor (e.g. SI by penicillin or aspirin). The clinical image of SI may vary from the monosymptomatic aspect (urticaria, vomiting, diarrhoea, headaches, etc.) to the one with complex symptomatology (mixed form). Usually the symptoms are dramatic and depend on the administration of a certain drug (often in SI of allergic origin) or of various drugs (mainly on non-immunologic form). The absence of vascular collapse differentiates SI from shock. Differential diagnosis is more difficult in border cases with a slight diminution of blood pressure. SI can be diagnosed especially in several circumstances: when the first adverse drug reaction is dramatic; when the first allergic-type reaction to a drug occurs; when the repetition of drug reactions is amplified in intensity or frequency; when it occurs in persons with risk factors. The differential diagnosis of SI is made with a crude or minimum shock and with pre-shock condition. The advantages of SI diagnosis are the institution of efficient treatment with rapid recoverability and the prevention of subsequent shock to the respective drug.", "contents": "Imminent shock; a useful diagnosis in drug pathology. A research has been carried out on a total of 121 persons with survival post-drug shock (DS), which registered 192 DS. Mention should be made of their predominance in the feminine sex (85 per cent) and their maximum frequency between the ages of 21-50 (average age 34). DS was the first adverse reaction to drugs in 71 per cent of the cases. Therefore DS unpredictability is very frequent. A retrospective study suggested the role of risk factors which should help the doctor to prevent DS (personal allergic antecedents, antecedents of adverse reactions to drugs, neuroses, disorders of endocrine glands, feminine sex, etc.). In 1970, the clinical concept of shock imminence (SI) was formulated and it is applied to various etiologies (drugs, insect stings, food). The existence of SI was identified in the case history of 14 per cent of the persons with DS. SI is a syndrome which includes all clinical manifestations with imminent potential of transformation into shock condition, and represents the stage precursory to the setting up of shock. The utility of SI diagnosis is maximum if it also includes the causal factor (e.g. SI by penicillin or aspirin). The clinical image of SI may vary from the monosymptomatic aspect (urticaria, vomiting, diarrhoea, headaches, etc.) to the one with complex symptomatology (mixed form). Usually the symptoms are dramatic and depend on the administration of a certain drug (often in SI of allergic origin) or of various drugs (mainly on non-immunologic form). The absence of vascular collapse differentiates SI from shock. Differential diagnosis is more difficult in border cases with a slight diminution of blood pressure. SI can be diagnosed especially in several circumstances: when the first adverse drug reaction is dramatic; when the first allergic-type reaction to a drug occurs; when the repetition of drug reactions is amplified in intensity or frequency; when it occurs in persons with risk factors. The differential diagnosis of SI is made with a crude or minimum shock and with pre-shock condition. The advantages of SI diagnosis are the institution of efficient treatment with rapid recoverability and the prevention of subsequent shock to the respective drug."}
{"id": "PMID:13652", "title": "Effect of methylated PGE2 analogs given orally on pancreatic response to secretin in man.", "content": "The effect of two methylated PGE2 analogs given orally on the pancreatic response to intravenous secretin has been studied in 8 healthy subjects. The secretion of bicarbonate was not changed by these PGE2 analogs. The secretion of enzymes during infusion of PGE2 analogs was significantly greater than in the control.", "contents": "Effect of methylated PGE2 analogs given orally on pancreatic response to secretin in man. The effect of two methylated PGE2 analogs given orally on the pancreatic response to intravenous secretin has been studied in 8 healthy subjects. The secretion of bicarbonate was not changed by these PGE2 analogs. The secretion of enzymes during infusion of PGE2 analogs was significantly greater than in the control."}
{"id": "PMID:13653", "title": "Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria.", "content": "A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate.", "contents": "Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria. A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate."}
{"id": "PMID:13654", "title": "Studies of glucose turnover and renal function in an unusual case of hereditary fructose intolerance.", "content": "Examination of glucose kinetics, pancreatic alpha and beta cell function, plasma lipids, urinary acidification and calcium excretion has been undertaken in a patient with hereditary fructose intolerance. This case was unusual as it was associated with insulin-requiring diabetes, type IV hyperlipemia, hypercalciuria and renal calculi. He also demonstrated the previously described fructose-induced defect of urine acidification. Glucagon and C-peptide assays showed that the pancreatic alpha cells were stimulated by fructose and that the beta cells did not respond to fructose. It is not known whether the latter was due to his diabetes or to the lack of a beta cell response to this sugar. Primed 14C-glucose infusions were used for the first time to study nonsteady state glucose kinetics in man. They showed that, 24 hours after the last insulin injection and under basal conditions, the glucose concentrations increased because glucose production exceeded glucose utilization. However, after the administration of sorbitol the plasma glucose concentration decreased because glucose production decreased. After the administration of sorbitol there was no change in the metabolic clearance of glucose. This reflects the lack of a peripheral insulin effect and is consistent with the lack of any measurable C-peptide. Glucose utilization also decreased, but this decrease was less than the decrease in glucose production. Because the metabolic clearance of glucose remained unchanged, it was concluded that the change in glucose utilization was solely due to the decrease in glucose concentration. The absence of C-peptide in the plasma indicated that changes in glucose turnover were not related to any changes in endogenous plasma insulin. Furthermore, the plasma glucagon concentration increased and, hence, changes in this hormone could not account for the decrease in glucose production. Therefore, it was concluded that the sorbitol-induced decline in glucose production was due to a direct effect on hepatic metabolism.", "contents": "Studies of glucose turnover and renal function in an unusual case of hereditary fructose intolerance. Examination of glucose kinetics, pancreatic alpha and beta cell function, plasma lipids, urinary acidification and calcium excretion has been undertaken in a patient with hereditary fructose intolerance. This case was unusual as it was associated with insulin-requiring diabetes, type IV hyperlipemia, hypercalciuria and renal calculi. He also demonstrated the previously described fructose-induced defect of urine acidification. Glucagon and C-peptide assays showed that the pancreatic alpha cells were stimulated by fructose and that the beta cells did not respond to fructose. It is not known whether the latter was due to his diabetes or to the lack of a beta cell response to this sugar. Primed 14C-glucose infusions were used for the first time to study nonsteady state glucose kinetics in man. They showed that, 24 hours after the last insulin injection and under basal conditions, the glucose concentrations increased because glucose production exceeded glucose utilization. However, after the administration of sorbitol the plasma glucose concentration decreased because glucose production decreased. After the administration of sorbitol there was no change in the metabolic clearance of glucose. This reflects the lack of a peripheral insulin effect and is consistent with the lack of any measurable C-peptide. Glucose utilization also decreased, but this decrease was less than the decrease in glucose production. Because the metabolic clearance of glucose remained unchanged, it was concluded that the change in glucose utilization was solely due to the decrease in glucose concentration. The absence of C-peptide in the plasma indicated that changes in glucose turnover were not related to any changes in endogenous plasma insulin. Furthermore, the plasma glucagon concentration increased and, hence, changes in this hormone could not account for the decrease in glucose production. Therefore, it was concluded that the sorbitol-induced decline in glucose production was due to a direct effect on hepatic metabolism."}
{"id": "PMID:13656", "title": "Evaluation of success in treatment of threatening premature labor by betamimetic drugs.", "content": "For prevention of premature labor the betasympathicomimetic drugs buphenin, fenoterol, and ritodrine were administered to 135 patients intravenously for 1 week and afterward orally up to the end of week 37 of gestation. No satisfactory evaluation of success could be obtained by analyzing only the time gained by the treatment. Two supplemental parameters were needed. In addition to the previously introduced Tocolysis Index (TI) which describes the obstetric situation at the beginning of the treatment, a Prolongation Index (PI) was defined transforming the lag time gained by the treatment into a relative measure. By means of this PI, extremely differing cases could be compared, though the gestational ages at the start of treatment and the lag times between admission and delivery showed wide variation. In addition, satisfactory statistical correlations between the PI and the clinical signs as well as the neonatal outcome could be computed, indicating the PI to be a suitable parameter for the estimation of success.", "contents": "Evaluation of success in treatment of threatening premature labor by betamimetic drugs. For prevention of premature labor the betasympathicomimetic drugs buphenin, fenoterol, and ritodrine were administered to 135 patients intravenously for 1 week and afterward orally up to the end of week 37 of gestation. No satisfactory evaluation of success could be obtained by analyzing only the time gained by the treatment. Two supplemental parameters were needed. In addition to the previously introduced Tocolysis Index (TI) which describes the obstetric situation at the beginning of the treatment, a Prolongation Index (PI) was defined transforming the lag time gained by the treatment into a relative measure. By means of this PI, extremely differing cases could be compared, though the gestational ages at the start of treatment and the lag times between admission and delivery showed wide variation. In addition, satisfactory statistical correlations between the PI and the clinical signs as well as the neonatal outcome could be computed, indicating the PI to be a suitable parameter for the estimation of success."}
{"id": "PMID:13657", "title": "Fetal breathing and adaptation to maternal hemorrhage in the sheep.", "content": "The effect of maternal hemorrhage in chronic preparations was studied on fetal lambs in the last month of gestation. Fourteen to 20 per cent of maternal blood was estimated to have been removed within 30 minutes, which resulted in a drop of 30 per cent of mean maternal arterial pressure. A fetal bradycardia started 28 +/- 13 minutes after the beginning of maternal hemorrhage. It lasted 30 +/- 15 minutes and was concomitant with a rise in fetal arterial pressure. It was followed by a long-lasting fetal tachycardia of 130 +/- 38 minutes and was corrected only by reinfusion of blood to the mother. The fetal blood gases demonstrated a mild asphyxia with a persistent metabolic acidemia until reinfusion of blood to the mother. Maternal and fetal plasma cortisol levels rose significantly at the end of the hemorrhage. Tracheal fluid flow did not change. Fetal breathing recorded 20 hours before and 24 hours after the experiment did not show consistent changes, but during fetal bradycardia there was no fetal breathing. Recent clinical investigations in this field have been made in the human fetus to estimate standards of fetal well being. These peculiar animal experiments do not show any significant improvement by recording fetal breathing over the recording of prelabor fetal heart rate.", "contents": "Fetal breathing and adaptation to maternal hemorrhage in the sheep. The effect of maternal hemorrhage in chronic preparations was studied on fetal lambs in the last month of gestation. Fourteen to 20 per cent of maternal blood was estimated to have been removed within 30 minutes, which resulted in a drop of 30 per cent of mean maternal arterial pressure. A fetal bradycardia started 28 +/- 13 minutes after the beginning of maternal hemorrhage. It lasted 30 +/- 15 minutes and was concomitant with a rise in fetal arterial pressure. It was followed by a long-lasting fetal tachycardia of 130 +/- 38 minutes and was corrected only by reinfusion of blood to the mother. The fetal blood gases demonstrated a mild asphyxia with a persistent metabolic acidemia until reinfusion of blood to the mother. Maternal and fetal plasma cortisol levels rose significantly at the end of the hemorrhage. Tracheal fluid flow did not change. Fetal breathing recorded 20 hours before and 24 hours after the experiment did not show consistent changes, but during fetal bradycardia there was no fetal breathing. Recent clinical investigations in this field have been made in the human fetus to estimate standards of fetal well being. These peculiar animal experiments do not show any significant improvement by recording fetal breathing over the recording of prelabor fetal heart rate."}
{"id": "PMID:13658", "title": "Secretory surface area and phosphatase activity of frog gastric mucosa.", "content": "Gastric mucosae were isolated from the European frog, R. temporaria, and after 5-7 h, stimulated with histamine (10(-4) M) and theophylline (5 mM). Acid secretion increased about fourfold, and this was accompanied by a threefold increase in secretory surface of the oxyntic cells, as determined in electron micrographs with conventional morphometric techniques. At the same time phosphatase activity of the secretory surface increased. Other experiments showed that the latter was due to an acid phosphatase, with pH optimum near 3. It appears that the increase in surface phosphatase with stimulation can be attributed to a diminished local pH and not to the increase in surface area demonstrated in this study.", "contents": "Secretory surface area and phosphatase activity of frog gastric mucosa. Gastric mucosae were isolated from the European frog, R. temporaria, and after 5-7 h, stimulated with histamine (10(-4) M) and theophylline (5 mM). Acid secretion increased about fourfold, and this was accompanied by a threefold increase in secretory surface of the oxyntic cells, as determined in electron micrographs with conventional morphometric techniques. At the same time phosphatase activity of the secretory surface increased. Other experiments showed that the latter was due to an acid phosphatase, with pH optimum near 3. It appears that the increase in surface phosphatase with stimulation can be attributed to a diminished local pH and not to the increase in surface area demonstrated in this study."}
{"id": "PMID:13659", "title": "HCO3 transport in rat jejunum: relationship to NaCl and H2O transport in vivo.", "content": "HCO3- absorption and its association with Na+ absorption has been studied in the rat jejunum in vivo, using a single-pass perfusion technique. The method of disequilibrium pH, the only valid way of demonstrating jejunal H+ secretion, was used to distinguish between an HCO3- pump and H+ secretion as the mechanism of HCO3- absorption. HCO3- stimulated Na+ absorption; Na+ deletion inhibited HCO3 absorption, decreased luminal acidification, and decreased the level of luminal PCO2. These results confirmed an Na+:H+ cation exchange, the possible mechanism of which is discussed in terms of results using other tissues. Na+-dependent HCO3-absorption made up a larger part of total HCO3-absorption as the luminal HCO3-concentrations diminished, although the precise degree of Na+-dependency could not be determined because of the unstirred layer effect. The mechanism of Na+-independent HCO3-absorption was not established, but it was not affected by PD, Cl-, or H2O movements. Glucose-stimulated and HCO3-stimulated Na+ absorption were less than additive. The physiological importance of HCO3-stimulated Na+ absorption in the acidic postprandial jejunum is probably due entirely to the effect of free CO2 in the lumen.", "contents": "HCO3 transport in rat jejunum: relationship to NaCl and H2O transport in vivo. HCO3- absorption and its association with Na+ absorption has been studied in the rat jejunum in vivo, using a single-pass perfusion technique. The method of disequilibrium pH, the only valid way of demonstrating jejunal H+ secretion, was used to distinguish between an HCO3- pump and H+ secretion as the mechanism of HCO3- absorption. HCO3- stimulated Na+ absorption; Na+ deletion inhibited HCO3 absorption, decreased luminal acidification, and decreased the level of luminal PCO2. These results confirmed an Na+:H+ cation exchange, the possible mechanism of which is discussed in terms of results using other tissues. Na+-dependent HCO3-absorption made up a larger part of total HCO3-absorption as the luminal HCO3-concentrations diminished, although the precise degree of Na+-dependency could not be determined because of the unstirred layer effect. The mechanism of Na+-independent HCO3-absorption was not established, but it was not affected by PD, Cl-, or H2O movements. Glucose-stimulated and HCO3-stimulated Na+ absorption were less than additive. The physiological importance of HCO3-stimulated Na+ absorption in the acidic postprandial jejunum is probably due entirely to the effect of free CO2 in the lumen."}
{"id": "PMID:13660", "title": "Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport.", "content": "Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate.", "contents": "Vitamin K1 intestinal absorption in vivo: influence of luminal contents on transport. Intestinal absorption of [3H]phylloquinone was investigated in the unanesthetized rat by the use of a technique of recirculating perfused isolated intestinal segments. Apparent saturation kinetics were found as the concentration of the vitamin in the perfusate was increased in a stepwise fashion from 15 nM to 300 muM. Alkalinization of the perfusate or the addition of 2.5 mM linoleic acid to the perfusate caused a significant (P less than 0.05) decrease in the absorption rate of phylloquinone. Modifications in the perfusate concentration of sodium taurocholate, the substitution of a nonionic detergent (Pluronic F-68) for sodium taurocholate, the addition of medium- and long-chain saturated fatty acids, or the addition of vitamins K2 and K3 to the perfusate did not alter the absorption rate of the vitamin. Decreasing the thickness of the unstirred water layer by increasing the perfusion rate caused a significant increase in phylloquinone absorption rate. In vivo absorption of vitamin K1 appears to be mediated by an energy requiring saturable transport mechanism. The composition of the perfusate, its pH, and its rate of flow are all important determinants of vitamin K1 absorption rate."}
{"id": "PMID:13661", "title": "Fluoride absorption from the rat urinary bladder: a pH-dependent event.", "content": "Urinary bladder absorption of stable and radiofluoride was studied as a function of pH in anesthetized rats to further evaluate the influence of pH gradients on fluoride transport. Buffered pH values and stable fluoride concentrations ranged from 1.85 to 7.90 and from 0.012 to 8.81 mM, respectively. [14c]inulin served as a marker for solute concentration changes due to water migration or dilution. The results indicate that bladder fluoride absorption is inversely related to pH over the 1.85-5.50 range. Mean, 15-min radiofluoride absorption values of 70% at pH 1,85, 37% at pH 3.95, and 5% at pH 5.50 WERE OBSERVED. These fractional absorption values were not significantly influenced by carrier fluoride concentration, the buffers used, or the presence of urine. Above pH 5.50, pH-independent absorption occurs to a slight extent. The results are consistent with a first-order absorptive process which occurs by the nonionic diffusion of hydrogen fluoride.", "contents": "Fluoride absorption from the rat urinary bladder: a pH-dependent event. Urinary bladder absorption of stable and radiofluoride was studied as a function of pH in anesthetized rats to further evaluate the influence of pH gradients on fluoride transport. Buffered pH values and stable fluoride concentrations ranged from 1.85 to 7.90 and from 0.012 to 8.81 mM, respectively. [14c]inulin served as a marker for solute concentration changes due to water migration or dilution. The results indicate that bladder fluoride absorption is inversely related to pH over the 1.85-5.50 range. Mean, 15-min radiofluoride absorption values of 70% at pH 1,85, 37% at pH 3.95, and 5% at pH 5.50 WERE OBSERVED. These fractional absorption values were not significantly influenced by carrier fluoride concentration, the buffers used, or the presence of urine. Above pH 5.50, pH-independent absorption occurs to a slight extent. The results are consistent with a first-order absorptive process which occurs by the nonionic diffusion of hydrogen fluoride."}
{"id": "PMID:13662", "title": "Effect of autonomic blockade on the hemodynamic findings in acute cardiac tamponade.", "content": "Twenty-three closed-chest, alpha-chloralose-anesthetized, volume-expanded, alpha- and beta-adrenergic-blockaded dogs with rate fixed by atrial pacing had 30-90 ml of saline at 37 degrees C infused into the pericardial sac a) with vagus intact, b) after vagotomy, and c) with vagus intact but with systolic pressure augmented with a balloon. A significant reduction in left ventricular (LV) systolic pressure (SP), and cardiac output (CO) occurred at a pericardial volume of 30-60 ml, when LV end-diastolic (ED) and right atrial (RA) pressures were not increased. Whereas the percentage decline of CO, LVSP, maximum negative and maximum positive dP/dt was greater in group A (vagus intact) than in group B (vagus cut), significant residual depressed performance was demonstrated only in group B. In four paced, atropinized, beta-blockaded dogs, response to tamponade was similar to that in intact dogs; vagotomy at 90 ml in these dogs resulted in a fall in CO, a rise of LVSP and a significant elevation in LVED and RA pressures. Thus, in the early phases of cardiac tamponade a sympathetic neurohumoral response supports cardiac performance while the vagus nerve exerts a myocardial protective effect. Vagal afferents appear to modulate this response.", "contents": "Effect of autonomic blockade on the hemodynamic findings in acute cardiac tamponade. Twenty-three closed-chest, alpha-chloralose-anesthetized, volume-expanded, alpha- and beta-adrenergic-blockaded dogs with rate fixed by atrial pacing had 30-90 ml of saline at 37 degrees C infused into the pericardial sac a) with vagus intact, b) after vagotomy, and c) with vagus intact but with systolic pressure augmented with a balloon. A significant reduction in left ventricular (LV) systolic pressure (SP), and cardiac output (CO) occurred at a pericardial volume of 30-60 ml, when LV end-diastolic (ED) and right atrial (RA) pressures were not increased. Whereas the percentage decline of CO, LVSP, maximum negative and maximum positive dP/dt was greater in group A (vagus intact) than in group B (vagus cut), significant residual depressed performance was demonstrated only in group B. In four paced, atropinized, beta-blockaded dogs, response to tamponade was similar to that in intact dogs; vagotomy at 90 ml in these dogs resulted in a fall in CO, a rise of LVSP and a significant elevation in LVED and RA pressures. Thus, in the early phases of cardiac tamponade a sympathetic neurohumoral response supports cardiac performance while the vagus nerve exerts a myocardial protective effect. Vagal afferents appear to modulate this response."}
{"id": "PMID:13663", "title": "Action of histamine and H1 and H2 blockers on the cardiopulmonary circulation.", "content": "Systemic and pulmonary hemodynamic responses to histamine were investigated inchronically instrumented unanesthetized nonpregnant ewes. Histamine was administered intravenously and into the pulmonary artery. The effects of the same doses of histamine were assessed following H1 and H2 receptor blockade. The effects ocular changes were also monitored. Results indicate that intravenous histamine produces tachycardia, systemic hypotension, pulmonary hypertension, and reduced cardiac output. The pulmonary response could be modified significantly by pentobarbital anesthesia. When injected directly into the pulmonary artery histamine failed to elicit any circulatory response. Blockade of H1 and H2 receptors, as well as autonomic ganglia, resulted in a comparable attentuation of the histamine circulatory response. It is concluded that a) central hemodynamic responses do not seem to be mediated through specific H1 and H2 receptors; b) histamine-induced pulmonary vasoconstriction can be reversed by pentobarbital anesthesia, and c) the absence of circulatory response to intrapulmonary histamine administration suggests that whatever receptors that may exist in the pulmonary vascular bed are not necessary for the central hemodynamic effects.", "contents": "Action of histamine and H1 and H2 blockers on the cardiopulmonary circulation. Systemic and pulmonary hemodynamic responses to histamine were investigated inchronically instrumented unanesthetized nonpregnant ewes. Histamine was administered intravenously and into the pulmonary artery. The effects of the same doses of histamine were assessed following H1 and H2 receptor blockade. The effects ocular changes were also monitored. Results indicate that intravenous histamine produces tachycardia, systemic hypotension, pulmonary hypertension, and reduced cardiac output. The pulmonary response could be modified significantly by pentobarbital anesthesia. When injected directly into the pulmonary artery histamine failed to elicit any circulatory response. Blockade of H1 and H2 receptors, as well as autonomic ganglia, resulted in a comparable attentuation of the histamine circulatory response. It is concluded that a) central hemodynamic responses do not seem to be mediated through specific H1 and H2 receptors; b) histamine-induced pulmonary vasoconstriction can be reversed by pentobarbital anesthesia, and c) the absence of circulatory response to intrapulmonary histamine administration suggests that whatever receptors that may exist in the pulmonary vascular bed are not necessary for the central hemodynamic effects."}
{"id": "PMID:13664", "title": "Physiologic effects of normal-or low-oxygen-affinity red cells in hypoxic baboons.", "content": "Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia.", "contents": "Physiologic effects of normal-or low-oxygen-affinity red cells in hypoxic baboons. Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia."}
{"id": "PMID:13665", "title": "Acid-base balance and plasma composition in the aestivating lungfish (Protopterus).", "content": "Upon entering into aestivation, Protopterus aethiopicus develops a respiratory acidosis. A slow compensatory increase in plasma bicarbonate suffices only to partially restore arterial pH toward normal. The cessation of water intake from the start of aestivation results in hemoconcentration and marked oliguria. The concentrations of most plasma constituents continue to increase progressively, and the electrolyte ratios change. The increase in urea concentration is disproportionately high for the degree of dehydration and constitutes an increasing fraction of total plasma osmolality. Acid-base and electrolyte balance do not reach a new equilibrium within 1 yr in the cocoon.", "contents": "Acid-base balance and plasma composition in the aestivating lungfish (Protopterus). Upon entering into aestivation, Protopterus aethiopicus develops a respiratory acidosis. A slow compensatory increase in plasma bicarbonate suffices only to partially restore arterial pH toward normal. The cessation of water intake from the start of aestivation results in hemoconcentration and marked oliguria. The concentrations of most plasma constituents continue to increase progressively, and the electrolyte ratios change. The increase in urea concentration is disproportionately high for the degree of dehydration and constitutes an increasing fraction of total plasma osmolality. Acid-base and electrolyte balance do not reach a new equilibrium within 1 yr in the cocoon."}
{"id": "PMID:13668", "title": "Secretory state of gastric mucosa and resistance to injury by exogenous acid.", "content": "The capacity of the stomach to resist the effects of highly acid solutions was assessed by comparing the effects of such solutions on spontaneously secreting, stimulated, and inhibited gastric mucosae of rabbits in vivo and frogs in vitro. Exposure of unstimulated resting mucosa to HC1, 120 mM, for 60 minutes produced superficial erosions in all rabbits, whereas such lesions were observed in only one of ten animals stimulated with histamine. Metiamide obviated the protective effect of histamine against ulcerations even though it did not reduce H+ secretion to zero. Exposure of inhibited isolated frog fundic mucosa to HC1 resulted in significant deterioration of electrical parameters, suggesting impairment of active transport processes and increased tissue permeability. These data are consistent with the hypothesis that actively secreting gastric mucosae from two species resist injury to exogenous acid more effectively than do resting or inhibited tissues, perhaps in part as a result of a greater alkaline tide.", "contents": "Secretory state of gastric mucosa and resistance to injury by exogenous acid. The capacity of the stomach to resist the effects of highly acid solutions was assessed by comparing the effects of such solutions on spontaneously secreting, stimulated, and inhibited gastric mucosae of rabbits in vivo and frogs in vitro. Exposure of unstimulated resting mucosa to HC1, 120 mM, for 60 minutes produced superficial erosions in all rabbits, whereas such lesions were observed in only one of ten animals stimulated with histamine. Metiamide obviated the protective effect of histamine against ulcerations even though it did not reduce H+ secretion to zero. Exposure of inhibited isolated frog fundic mucosa to HC1 resulted in significant deterioration of electrical parameters, suggesting impairment of active transport processes and increased tissue permeability. These data are consistent with the hypothesis that actively secreting gastric mucosae from two species resist injury to exogenous acid more effectively than do resting or inhibited tissues, perhaps in part as a result of a greater alkaline tide."}
{"id": "PMID:13669", "title": "Effects of chronic hypoxia on canine gastric secretion.", "content": "Interdigestive gastirc acid output and acid secretory response to histamine, insulin  and pentagastrin were studied in five dogs before and after creation of a right to left extracardiac vascular shunt. The arterial PO2 decreased from 81.5 +/- 5.5 mm Hg to 39.8 +/- 6.0 mm Hg postoperatively with no change in arterial pH or PaCO2. Basal (interdigestive) acid output increased from 1.19 +/- 0.26 mEq/hr to 4.97 +/- 0.81 mEq/hr postoperatively. Acid secretory response to insulin was increased after the induction of chronic hypoxia. Increased sensitivity to pentagastric was also observed although parietal cell mass (maximum histamine-stimulated output) was unchanged postoperatively. Changes in acid secretory response and PaO2 were present at one week and were sustained through twelve weeks after shunting. Chronic hypoxia resulted in gastric acid hypersecretion secondary to enhanced sensitivity of the parietal cell to a combination of neural and humoral stimuli.", "contents": "Effects of chronic hypoxia on canine gastric secretion. Interdigestive gastirc acid output and acid secretory response to histamine, insulin  and pentagastrin were studied in five dogs before and after creation of a right to left extracardiac vascular shunt. The arterial PO2 decreased from 81.5 +/- 5.5 mm Hg to 39.8 +/- 6.0 mm Hg postoperatively with no change in arterial pH or PaCO2. Basal (interdigestive) acid output increased from 1.19 +/- 0.26 mEq/hr to 4.97 +/- 0.81 mEq/hr postoperatively. Acid secretory response to insulin was increased after the induction of chronic hypoxia. Increased sensitivity to pentagastric was also observed although parietal cell mass (maximum histamine-stimulated output) was unchanged postoperatively. Changes in acid secretory response and PaO2 were present at one week and were sustained through twelve weeks after shunting. Chronic hypoxia resulted in gastric acid hypersecretion secondary to enhanced sensitivity of the parietal cell to a combination of neural and humoral stimuli."}
{"id": "PMID:13673", "title": "The redox state of the glutathione in the bovine corneal epithelium.", "content": "In the corneal epithelium the levels of the oxidized and reduced glutathione, the oxidized and reduced triphosphopyridine nucleotide, the glucose-6-phosphate and the 6-phosphogluconate were investigated. The in vivo steady state levels were defined by preparation procedures and by the energy state of the adenosine phosphate system. The ratios of the levels of the metabolites involved suggested that the reactions of the glucose-6-phosphate dehydrogenase and of the glutathione reductase operate dependent on the redox state of the triphosphopyridine nucleotides.", "contents": "The redox state of the glutathione in the bovine corneal epithelium. In the corneal epithelium the levels of the oxidized and reduced glutathione, the oxidized and reduced triphosphopyridine nucleotide, the glucose-6-phosphate and the 6-phosphogluconate were investigated. The in vivo steady state levels were defined by preparation procedures and by the energy state of the adenosine phosphate system. The ratios of the levels of the metabolites involved suggested that the reactions of the glucose-6-phosphate dehydrogenase and of the glutathione reductase operate dependent on the redox state of the triphosphopyridine nucleotides."}
{"id": "PMID:13677", "title": "Acid-base balance and blood gases changes and \"lactate excess\" in acute respiratory alkalosis during general anaesthesia.", "content": "In 40 young males aged 18-20 years operated on for inguinal hernioplasty acute respiratory alkalosis was obtained in the 45th minute of general anaesthesia. The values of basic acid-base balance parameters, blood gases, pyruvate and lactate levels and \"lactate excess\" were determined before and after hyperventilation. Shifts in the concentrations of hydrogen and bicarbonate ions were found which are both typical of acute respiratory alkalosis. No changes were observed in the oxygenation of capillary blood and the values of \"lactate excess\" were normal which rules out tissue hypoxia during acute respiratory alkalosis. Passive hyperventilation being a less dangerous alternative of hypoventilation is a frequent occurrence during general anaesthesia and it causes transient respiratory alkalosis.", "contents": "Acid-base balance and blood gases changes and \"lactate excess\" in acute respiratory alkalosis during general anaesthesia. In 40 young males aged 18-20 years operated on for inguinal hernioplasty acute respiratory alkalosis was obtained in the 45th minute of general anaesthesia. The values of basic acid-base balance parameters, blood gases, pyruvate and lactate levels and \"lactate excess\" were determined before and after hyperventilation. Shifts in the concentrations of hydrogen and bicarbonate ions were found which are both typical of acute respiratory alkalosis. No changes were observed in the oxygenation of capillary blood and the values of \"lactate excess\" were normal which rules out tissue hypoxia during acute respiratory alkalosis. Passive hyperventilation being a less dangerous alternative of hypoventilation is a frequent occurrence during general anaesthesia and it causes transient respiratory alkalosis."}
{"id": "PMID:13678", "title": "The effect of adrenergic receptor blocking agents on arrhythmia caused by trauma.", "content": "Experiments on animals have shown that blunt trauma to the anterior chest wall causes arrhythmia and conduction disturbances. In most cases nodal rhythm and ST segment elevation were observed. Microscopic examination disclosed myocardial damage in the vicinity of the atrioventricular node. Administration of alpha or beta adrenergic receptor blocking agents immediately before trauma failed to prevent arrhythmia and conduction disturbances, on the contrary, they became even more pronounced.", "contents": "The effect of adrenergic receptor blocking agents on arrhythmia caused by trauma. Experiments on animals have shown that blunt trauma to the anterior chest wall causes arrhythmia and conduction disturbances. In most cases nodal rhythm and ST segment elevation were observed. Microscopic examination disclosed myocardial damage in the vicinity of the atrioventricular node. Administration of alpha or beta adrenergic receptor blocking agents immediately before trauma failed to prevent arrhythmia and conduction disturbances, on the contrary, they became even more pronounced."}
{"id": "PMID:13682", "title": "General anesthetics and regional hypoxic pulmonary vasoconstriction.", "content": "Administration of N2O, fluroxene and isoflurane to the left lower lobe (LLL) of dogs anesthetized with pentobarbital was previously shown to inhibit LLL hypoxic pulmonary vasoconstriction (HPV). Using the same experimental model, the present study examined the effect of whole-lung administration of N2O, fluroxene, isoflurane, halothane, and enflurane on left-lower-lobe HPV. Selective ventilation of the LLL with N2 alone caused blood flow to the lobe to decrease 53.3 +/- 3.0 per cent. Responses to LLL hypoxia were remeasured during administration of inhalation anesthetics at 1 and 2 MAC to both the LLL and the rest of the lung. Isoflurane and fluroxene progressively inhibited and at 2 MAC halved lobar HPV. N2O (one third MAC) caused slight but significant inhibition, while halothane and enflurane caused slight and nonsignificant changes in lobar HPV. These effects of whole-lung administration of anesthetics on HPV were almost identical to those obtained when the administration was confined to the test lobe alone. It is concluded that N2O, isoflurane, and fluroxene locally inhibit regional HPV and via this mechanism increase total venous admixture, while halothane and enflurane do not have this effect.", "contents": "General anesthetics and regional hypoxic pulmonary vasoconstriction. Administration of N2O, fluroxene and isoflurane to the left lower lobe (LLL) of dogs anesthetized with pentobarbital was previously shown to inhibit LLL hypoxic pulmonary vasoconstriction (HPV). Using the same experimental model, the present study examined the effect of whole-lung administration of N2O, fluroxene, isoflurane, halothane, and enflurane on left-lower-lobe HPV. Selective ventilation of the LLL with N2 alone caused blood flow to the lobe to decrease 53.3 +/- 3.0 per cent. Responses to LLL hypoxia were remeasured during administration of inhalation anesthetics at 1 and 2 MAC to both the LLL and the rest of the lung. Isoflurane and fluroxene progressively inhibited and at 2 MAC halved lobar HPV. N2O (one third MAC) caused slight but significant inhibition, while halothane and enflurane caused slight and nonsignificant changes in lobar HPV. These effects of whole-lung administration of anesthetics on HPV were almost identical to those obtained when the administration was confined to the test lobe alone. It is concluded that N2O, isoflurane, and fluroxene locally inhibit regional HPV and via this mechanism increase total venous admixture, while halothane and enflurane do not have this effect."}
{"id": "PMID:13683", "title": "Control of breathing using an extracorporeal membrane lung.", "content": "Various amounts of carbon dioxide were removed through an extracorporeal membrane lung in spontaneously breathing lambs. The decrease in alveolar ventilation was proportional to the fraction of total carbon dioxide removed by the membrane lung. When extracorporeal CO2 removal approximated CO2 production (VCO2), alveolar ventilation almost ceased. Pulmonary ventilation can be controlled by extracorporeal carbon dioxide removal.", "contents": "Control of breathing using an extracorporeal membrane lung. Various amounts of carbon dioxide were removed through an extracorporeal membrane lung in spontaneously breathing lambs. The decrease in alveolar ventilation was proportional to the fraction of total carbon dioxide removed by the membrane lung. When extracorporeal CO2 removal approximated CO2 production (VCO2), alveolar ventilation almost ceased. Pulmonary ventilation can be controlled by extracorporeal carbon dioxide removal."}
{"id": "PMID:13684", "title": "Kinetic analysis of the AH8165-receptor interaction at the mammalian neuromuscular junction.", "content": "The effect of a new neuromuscular blocking agent, AH8165, on carbachol-induced end-plate depolarization was measured in isolated guinea pig lumbrical muscles. The results showed that the kinetics were competitive (parallel shift of dose-response curves to the right and a slope of Schild plot of 1.09 +/- 0.07) and the AH8165-receptor dissociation constant was estimated as 0.337 +/- 0.008 muM. Once the dissociation constant was known, the fraction of receptors occupied by any given concentration of AH8165 could be determined. This fractional receptor occupancy was then compared with the indirect twitch response in an isolated guinea pig nerve-lumbrical muscle preparation. These measurements of the effect of AH8165 on the margin of safety of neuromuscular transmission gave values comparable to those obtained with d-tubocurarine, i.e., the twitch remained normal until 75-80 per cent of the receptors were blocked and was abolished when 90-95 per cent of the receptors were occluded. Thus, the neuromuscular blocking action of AH8165 appears to be consistent with a simple postsynaptic competitive interaction with the transmitter.", "contents": "Kinetic analysis of the AH8165-receptor interaction at the mammalian neuromuscular junction. The effect of a new neuromuscular blocking agent, AH8165, on carbachol-induced end-plate depolarization was measured in isolated guinea pig lumbrical muscles. The results showed that the kinetics were competitive (parallel shift of dose-response curves to the right and a slope of Schild plot of 1.09 +/- 0.07) and the AH8165-receptor dissociation constant was estimated as 0.337 +/- 0.008 muM. Once the dissociation constant was known, the fraction of receptors occupied by any given concentration of AH8165 could be determined. This fractional receptor occupancy was then compared with the indirect twitch response in an isolated guinea pig nerve-lumbrical muscle preparation. These measurements of the effect of AH8165 on the margin of safety of neuromuscular transmission gave values comparable to those obtained with d-tubocurarine, i.e., the twitch remained normal until 75-80 per cent of the receptors were blocked and was abolished when 90-95 per cent of the receptors were occluded. Thus, the neuromuscular blocking action of AH8165 appears to be consistent with a simple postsynaptic competitive interaction with the transmitter."}
{"id": "PMID:13681", "title": "Comparison of THAM and sodium bicarbonate in resuscitation of the heart after ventricular fibrillation in dogs.", "content": "Tris (hydroxymethyl) aminomethane (tromethamine or THAM) has been suggested as an effective substitute for sodium bicarbonate (NaHCO3) in the treatment of metabolic acidosis accompanying cardiac arrest. Even though several reports on its appraisal have been published, there is still no clear agreement on its therapeutic value. A double-blind study was therefore lndertaken to compare in 36 dogs the effectiveness of 0.6 M THAM, 0.3 M THAM, and NaHCO3 (0.892 mEq/ml) to correct metabolic acidosis produced during 3 minutes of cardiac fibrillation, followed by a 3-minute period of cardiac compression. The dogs were then defibrillated and observed for 45 minutes. One group of 8 dogs was treated with 0.9 percent NaCl infusion. Compared with 0.9 percent NaCl, both THAM and NaHCO3 were equally effective in correcting metabolic acidosis (p less than 0.05). Initially, 0.6 M THAM produced a more pronounced (p less than 0.05) elevation of blood pH, but this effect was not sustained during the later postdefibrillation period. There was little difference in the effect of either of these drugs on mean aortic pressure and total peripheral vascular resistance. It is concluded that adequate ventilation and effective cardiac compression are still the chief criteria on which the final outcome of cardiac resuscitation depends. Correction of metabolic acidosis is important supportive therapy, but either THAM or NaHCO3 can be used with comparatively equivalent effect.", "contents": "Comparison of THAM and sodium bicarbonate in resuscitation of the heart after ventricular fibrillation in dogs. Tris (hydroxymethyl) aminomethane (tromethamine or THAM) has been suggested as an effective substitute for sodium bicarbonate (NaHCO3) in the treatment of metabolic acidosis accompanying cardiac arrest. Even though several reports on its appraisal have been published, there is still no clear agreement on its therapeutic value. A double-blind study was therefore lndertaken to compare in 36 dogs the effectiveness of 0.6 M THAM, 0.3 M THAM, and NaHCO3 (0.892 mEq/ml) to correct metabolic acidosis produced during 3 minutes of cardiac fibrillation, followed by a 3-minute period of cardiac compression. The dogs were then defibrillated and observed for 45 minutes. One group of 8 dogs was treated with 0.9 percent NaCl infusion. Compared with 0.9 percent NaCl, both THAM and NaHCO3 were equally effective in correcting metabolic acidosis (p less than 0.05). Initially, 0.6 M THAM produced a more pronounced (p less than 0.05) elevation of blood pH, but this effect was not sustained during the later postdefibrillation period. There was little difference in the effect of either of these drugs on mean aortic pressure and total peripheral vascular resistance. It is concluded that adequate ventilation and effective cardiac compression are still the chief criteria on which the final outcome of cardiac resuscitation depends. Correction of metabolic acidosis is important supportive therapy, but either THAM or NaHCO3 can be used with comparatively equivalent effect."}
{"id": "PMID:13685", "title": "[Drugs combined with neuroleptics in anesthesia].", "content": "The neuroleptics are characterised by the large number of pharmacological effects they develop. When they are associated with other substances, it is frequent for the latter to have with neuroleptics one or several common sites of action. At this level, they develop phenomena of drug interaction, for example, synergy with depressors of the central nervous system or, in the periphery, with alpha-adrenolytic or parasympatholytic drugs. This type of interaction is used in anesthesia to obtain more intense effects with lesser doses of each component and also avoid the toxic effects of efficacious doses of general anesthetics used alone. However, although certain interactions are useful, others may prove harmful. This is in particular the case where neuroleptic drugs are administered after ingestion of alcohol. Various mechanisms, central and peripheral, explain the marked depression of the central nervous system which results. Potentialisation of the effects of tricyclic antidepressor drugs by neuroleptics raises a difficult problem for the anesthetist, the elimination of tricyclic antidepressor drugs is slow and requires several weeks after stopping treatment. During this period, the tissue and plasma concentrations become reduced gradually. They are pharmacologically insufficient, but are potentialised by injection of neuroleptic drugs, and may become active again, and even toxic. It seems to us advisable to avoid the use of neuroleptic drugs in patients treated with tricyclic antidepressor drugs and, if necessary, to use another method of anesthesia.", "contents": "[Drugs combined with neuroleptics in anesthesia]. The neuroleptics are characterised by the large number of pharmacological effects they develop. When they are associated with other substances, it is frequent for the latter to have with neuroleptics one or several common sites of action. At this level, they develop phenomena of drug interaction, for example, synergy with depressors of the central nervous system or, in the periphery, with alpha-adrenolytic or parasympatholytic drugs. This type of interaction is used in anesthesia to obtain more intense effects with lesser doses of each component and also avoid the toxic effects of efficacious doses of general anesthetics used alone. However, although certain interactions are useful, others may prove harmful. This is in particular the case where neuroleptic drugs are administered after ingestion of alcohol. Various mechanisms, central and peripheral, explain the marked depression of the central nervous system which results. Potentialisation of the effects of tricyclic antidepressor drugs by neuroleptics raises a difficult problem for the anesthetist, the elimination of tricyclic antidepressor drugs is slow and requires several weeks after stopping treatment. During this period, the tissue and plasma concentrations become reduced gradually. They are pharmacologically insufficient, but are potentialised by injection of neuroleptic drugs, and may become active again, and even toxic. It seems to us advisable to avoid the use of neuroleptic drugs in patients treated with tricyclic antidepressor drugs and, if necessary, to use another method of anesthesia."}
{"id": "PMID:13686", "title": "[The origin and success of neuroleptics].", "content": "The authors retrace the origin and the development of the idea of neurolepsy in anesthesiology, first under the influence of Laborit, and in psychiatry, under the influence of Delay and Deniker, during the early 1950's. In these two fields, neuroleptic drugs were considered contrary to ideas and practice at that time and disturbed current ideas.", "contents": "[The origin and success of neuroleptics]. The authors retrace the origin and the development of the idea of neurolepsy in anesthesiology, first under the influence of Laborit, and in psychiatry, under the influence of Delay and Deniker, during the early 1950's. In these two fields, neuroleptic drugs were considered contrary to ideas and practice at that time and disturbed current ideas."}
{"id": "PMID:13688", "title": "[Neuroplegia: results of an interdisciplinary approach to its physiopathology].", "content": "Neuroplegia was born from a physiopathological study of states of shock and research on inhibition of the autonomic reaction to aggression. Over the last 25 years, the experimental facts have become accumulated in favour of the first theory of H. Laborit, i.e. that this so-called defence reaction defended our lives only through conservation of motor activity in the environment. When this motor activity is inefficacious or useless, the neuroendocrine reaction may lead, during the acute phase, to states of shock and to chronic psychosomatic pathology. On this general theme, inhibition of this reaction by neuroplegic drugs, among which the phenothiazine derivatives have played a very important role, has led in numerous surgical and medical disciplines, to basic research and therapeutic consequences. Thus, in anesthetics, it was at the origin of potentialised anesthesia, then neuroleptanalgesia. In general intensive care, it is used in various ways in the study and treatment of states of shock. In psychiatry, it has initiated neuro-psychopharmacology and the neuro-physiological and biochemical study of the nervous system in its response to the psycho-social environment. It has found its place in anesthesia and in obstetric pathology. But above all, has led pharmacologists to the study of metabolic and biochemical activities. The result of an interdisciplinary approach, neuroplegia has on the contrary, often been the origin of an interdisciplinary development of our physiological and physiopathological knowledge. Today this development seems to better understand its mode of action at various levels of organisation of living systems. One may thus say that neuroplegia, apart from its therapeutic interest, has been a good working instrument and led to better understanding of numerous biological disciplines.", "contents": "[Neuroplegia: results of an interdisciplinary approach to its physiopathology]. Neuroplegia was born from a physiopathological study of states of shock and research on inhibition of the autonomic reaction to aggression. Over the last 25 years, the experimental facts have become accumulated in favour of the first theory of H. Laborit, i.e. that this so-called defence reaction defended our lives only through conservation of motor activity in the environment. When this motor activity is inefficacious or useless, the neuroendocrine reaction may lead, during the acute phase, to states of shock and to chronic psychosomatic pathology. On this general theme, inhibition of this reaction by neuroplegic drugs, among which the phenothiazine derivatives have played a very important role, has led in numerous surgical and medical disciplines, to basic research and therapeutic consequences. Thus, in anesthetics, it was at the origin of potentialised anesthesia, then neuroleptanalgesia. In general intensive care, it is used in various ways in the study and treatment of states of shock. In psychiatry, it has initiated neuro-psychopharmacology and the neuro-physiological and biochemical study of the nervous system in its response to the psycho-social environment. It has found its place in anesthesia and in obstetric pathology. But above all, has led pharmacologists to the study of metabolic and biochemical activities. The result of an interdisciplinary approach, neuroplegia has on the contrary, often been the origin of an interdisciplinary development of our physiological and physiopathological knowledge. Today this development seems to better understand its mode of action at various levels of organisation of living systems. One may thus say that neuroplegia, apart from its therapeutic interest, has been a good working instrument and led to better understanding of numerous biological disciplines."}
{"id": "PMID:13690", "title": "[Neurophysiologic justification of the place of neuroleptics in neuroleptanalgesia].", "content": "We studied the action of drugs on the cortical and systemic hemodynamic responses to reticular stimulation and somatic nociceptive stimulation. Central analgesics, even in high dosage, do not suppress the awakening reaction and the attack of hypertension produced by sciatic stimulation in curarised cats. The addition of a neuroplegic, such as Droperidol or Ethrane in low dosage, abolishes completely the response to painful stimulation. The action of pure analgesic anesthesia seems to be situated, above all, at spinal level.", "contents": "[Neurophysiologic justification of the place of neuroleptics in neuroleptanalgesia]. We studied the action of drugs on the cortical and systemic hemodynamic responses to reticular stimulation and somatic nociceptive stimulation. Central analgesics, even in high dosage, do not suppress the awakening reaction and the attack of hypertension produced by sciatic stimulation in curarised cats. The addition of a neuroplegic, such as Droperidol or Ethrane in low dosage, abolishes completely the response to painful stimulation. The action of pure analgesic anesthesia seems to be situated, above all, at spinal level."}
{"id": "PMID:13691", "title": "[Endocrine effects of neuroleptics].", "content": "The neuroleptic drugs used in anesthetics belong to the group of phenothiazines or butyrophenones. The endocrine response to their intravenous administration is still ill-known and usually only concerns the association of anesthetics and neuroleptics. However, as far as the catecholamines are concerned, it is known that neuroleptic drugs do not prevent either their secretion nor their liberation but, depending on their dosage, they block the dopaminergic receptors and the alpha-receptors and induce disturbances in the metabolism of the mono-amines. The injection of neuroleptics associated with analgesics, raises the blood levels of catecholamines, does not induce a rise in ACTH and cortisol levels in the absence of stress, but does not totally prevent their rise in cases of aggression. As far as growth hormone is concerned, the effects are variable depending on the association studied. There is a rise with droperidol + pethidine or pentazocine, no change with chloroprotixene-dextromoramide. In both cases, the blood sugar rises. As far as STH, or growth hormone, free fatty acids and insulin are concerned, one may note a rise with associations containing droperidol even in the absence of any stress and stability with  a mixture of chlorprotixene and dextromoramide. With none of these well known associations was there any variation either in levels of pituitary thyreo-stimulin, nor in thyroxine levels. Testosterone becomes reduced with the association of droperidol + analgesics but this effect does not seem to be specific to droperidol. These responses are frequently disturbed in case of additional stress.", "contents": "[Endocrine effects of neuroleptics]. The neuroleptic drugs used in anesthetics belong to the group of phenothiazines or butyrophenones. The endocrine response to their intravenous administration is still ill-known and usually only concerns the association of anesthetics and neuroleptics. However, as far as the catecholamines are concerned, it is known that neuroleptic drugs do not prevent either their secretion nor their liberation but, depending on their dosage, they block the dopaminergic receptors and the alpha-receptors and induce disturbances in the metabolism of the mono-amines. The injection of neuroleptics associated with analgesics, raises the blood levels of catecholamines, does not induce a rise in ACTH and cortisol levels in the absence of stress, but does not totally prevent their rise in cases of aggression. As far as growth hormone is concerned, the effects are variable depending on the association studied. There is a rise with droperidol + pethidine or pentazocine, no change with chloroprotixene-dextromoramide. In both cases, the blood sugar rises. As far as STH, or growth hormone, free fatty acids and insulin are concerned, one may note a rise with associations containing droperidol even in the absence of any stress and stability with  a mixture of chlorprotixene and dextromoramide. With none of these well known associations was there any variation either in levels of pituitary thyreo-stimulin, nor in thyroxine levels. Testosterone becomes reduced with the association of droperidol + analgesics but this effect does not seem to be specific to droperidol. These responses are frequently disturbed in case of additional stress."}
{"id": "PMID:13692", "title": "[Sympathetic-adrenergic and hypophysial response to different anesthesia-analgesia technics].", "content": "The authors used techniques of pure anesthesia analgesia with Fentathienyl-Pavulon, or anesthesia and analgesia potentialised with Fentathienyl-Flunitrazepam, or Pentothal-Fentathienyl-Pavulon on various series of patients. The study was oriented on changes in the sympathetico-adrenalin pituitary response, and the use of glucose under the effect of these techniques. There was noted a fall in plasma cortisol levels, a fall in urinary excretion of catecholamines, an increase in growth hormone and better peripheral use of glucose. A comparative study was carried out with similar techniques using morphine, pentazocine or fentanyl.", "contents": "[Sympathetic-adrenergic and hypophysial response to different anesthesia-analgesia technics]. The authors used techniques of pure anesthesia analgesia with Fentathienyl-Pavulon, or anesthesia and analgesia potentialised with Fentathienyl-Flunitrazepam, or Pentothal-Fentathienyl-Pavulon on various series of patients. The study was oriented on changes in the sympathetico-adrenalin pituitary response, and the use of glucose under the effect of these techniques. There was noted a fall in plasma cortisol levels, a fall in urinary excretion of catecholamines, an increase in growth hormone and better peripheral use of glucose. A comparative study was carried out with similar techniques using morphine, pentazocine or fentanyl."}
{"id": "PMID:13693", "title": "[Limits of pure analgesic anesthesia].", "content": "Before dealing with this subject, the author believes that it is useful to give a definition of this technique and justify it. He then recalls the results which he obtained with various analgesic drugs, few products permit this technique, either because of too low analgesic power, or because of the appearance in high dosage, of troublesome or dangerous side-effects. At present, in this type of anesthetic, one may use either morphine or fentanyl or fentathienyl. Analgesic anesthesia with morphine. This technique presents advantages and disadvantages. The author has no personal experience of high doses of morphine and can only report that of other authors who have studied this problem. Anesthesia analgesia with fentanyl and fentathienyl. The author believes that this technique presents advantages over the previous technique, he has personally studied the clinical pharmacology of high doses of fentanyl and he believes that this drug used by the intravenous route, at a dose of 0.05 mg/kg associated with a curare derivative, possesses favourable cardiovascular and respiratory metabolic effects during the surgical operation, but one must recognize that +/-20 p. 100 of cases, fentanyl associated only with curare is not sufficient to give a stable anesthetic. At present, the author has replaced, in his technique, fentanyl by fentathienyl which is a morphine derivative 6 to 7 times more powerful. He found with this drug most of the properties of high doses of fentanyl but the analgesia obtained is deeper, one does not find more than 20 p. 100 of resistant cases. However, the author noted the fairly frequent appearance of tachycardia for which there was no valid explanation. In conclusion. The author believes that in the reproaches which are made to analgesic anesthesia, some are justified, others are less so. It requires prolonged post-operative supervision, but the latter would be advisable for any other type of anesthesia. It dose not always permit one, in its pure form, to obtain stable anesthesia, but this is less and less true with the appearance of more and more powerful derivatives. The use of analgesic anesthesia as a routine technique is only possible in the form of sequential analgesic anesthesia, a technique which uses an antimorphine drug to awaken the patient. In this field, various new products are presented are discussed.", "contents": "[Limits of pure analgesic anesthesia]. Before dealing with this subject, the author believes that it is useful to give a definition of this technique and justify it. He then recalls the results which he obtained with various analgesic drugs, few products permit this technique, either because of too low analgesic power, or because of the appearance in high dosage, of troublesome or dangerous side-effects. At present, in this type of anesthetic, one may use either morphine or fentanyl or fentathienyl. Analgesic anesthesia with morphine. This technique presents advantages and disadvantages. The author has no personal experience of high doses of morphine and can only report that of other authors who have studied this problem. Anesthesia analgesia with fentanyl and fentathienyl. The author believes that this technique presents advantages over the previous technique, he has personally studied the clinical pharmacology of high doses of fentanyl and he believes that this drug used by the intravenous route, at a dose of 0.05 mg/kg associated with a curare derivative, possesses favourable cardiovascular and respiratory metabolic effects during the surgical operation, but one must recognize that +/-20 p. 100 of cases, fentanyl associated only with curare is not sufficient to give a stable anesthetic. At present, the author has replaced, in his technique, fentanyl by fentathienyl which is a morphine derivative 6 to 7 times more powerful. He found with this drug most of the properties of high doses of fentanyl but the analgesia obtained is deeper, one does not find more than 20 p. 100 of resistant cases. However, the author noted the fairly frequent appearance of tachycardia for which there was no valid explanation. In conclusion. The author believes that in the reproaches which are made to analgesic anesthesia, some are justified, others are less so. It requires prolonged post-operative supervision, but the latter would be advisable for any other type of anesthesia. It dose not always permit one, in its pure form, to obtain stable anesthesia, but this is less and less true with the appearance of more and more powerful derivatives. The use of analgesic anesthesia as a routine technique is only possible in the form of sequential analgesic anesthesia, a technique which uses an antimorphine drug to awaken the patient. In this field, various new products are presented are discussed."}
{"id": "PMID:13695", "title": "[Definition of the antineurotic, antipsychotic, neuroplegic and neuroleptic properties of psychotropic substances used in anesthesia and resuscitation].", "content": "There is a great deal of evidences (pharmacological, experimental and clinical, therapeutic, biological, biochemical, metabolic, toxicological and neurophysiological) which permits one to characterise among the psychotropic substances, the antineurotic or antipsychotic properties of certain psycholeptic drugs.  They authorize also the differentiation in the sub-group of \"antipsychotics\" of substances with a dominant neuroplegic or neuroleptic activity and others, such as lithium, which do not have this activity. This revision of the terminology avoids the confusion maintained by the use of terms \"tranquillisers\" and \"neuroleptics\" in the classification of psychotropic drugs.", "contents": "[Definition of the antineurotic, antipsychotic, neuroplegic and neuroleptic properties of psychotropic substances used in anesthesia and resuscitation]. There is a great deal of evidences (pharmacological, experimental and clinical, therapeutic, biological, biochemical, metabolic, toxicological and neurophysiological) which permits one to characterise among the psychotropic substances, the antineurotic or antipsychotic properties of certain psycholeptic drugs.  They authorize also the differentiation in the sub-group of \"antipsychotics\" of substances with a dominant neuroplegic or neuroleptic activity and others, such as lithium, which do not have this activity. This revision of the terminology avoids the confusion maintained by the use of terms \"tranquillisers\" and \"neuroleptics\" in the classification of psychotropic drugs."}
{"id": "PMID:13696", "title": "Bone marrow transplantation with intensive combination chemotherapy/radiation therapy (SCARI) in acute leukemia.", "content": "Fifteen patients with acute leukemia resistant to standard chemotherapy were treated by bone marrow transplantation from HLA-matched siblings after conditioning with a new combination chemotherapy/radiation therapy regimen--SCARI. SCARI consists of 5 days of high-dose cytosine arabinoside and 6-thioguanine followed by 3 days of daunorubicin. After a rest period, cyclophosphamide and total-body irradiation are given sequentially. This regimen had acceptable morbidity. Median survival was 169 days. Overall survival and disease-free survival was 27% at over 11 months. Relapse rate was 13% of the entire group and 30% by actuarial projection. Relapses were late and initially extramedullary. Deaths from causes other than leukemia occurred early secondary to fungal infection and late secondary to interstitial pneumonia (frequently cytomegalovirus). Graft-versus-host disease and graft rejection were not causes of mortality. In these patients conditioned with SCARI, leukemic recurrences were infrequent but infectious complications were a major hazard.", "contents": "Bone marrow transplantation with intensive combination chemotherapy/radiation therapy (SCARI) in acute leukemia. Fifteen patients with acute leukemia resistant to standard chemotherapy were treated by bone marrow transplantation from HLA-matched siblings after conditioning with a new combination chemotherapy/radiation therapy regimen--SCARI. SCARI consists of 5 days of high-dose cytosine arabinoside and 6-thioguanine followed by 3 days of daunorubicin. After a rest period, cyclophosphamide and total-body irradiation are given sequentially. This regimen had acceptable morbidity. Median survival was 169 days. Overall survival and disease-free survival was 27% at over 11 months. Relapse rate was 13% of the entire group and 30% by actuarial projection. Relapses were late and initially extramedullary. Deaths from causes other than leukemia occurred early secondary to fungal infection and late secondary to interstitial pneumonia (frequently cytomegalovirus). Graft-versus-host disease and graft rejection were not causes of mortality. In these patients conditioned with SCARI, leukemic recurrences were infrequent but infectious complications were a major hazard."}
{"id": "PMID:13697", "title": "Effect of sera from immunologically altered mice on phytohemagglutinin-induced mouse lymphocyte transformation.", "content": "The DNA-synthetic response of mouse spleen cells to phytohemagglutinin in vitro is depressed by the addition of normal mouse serum. The effects of sera from mice that had been modified immunologically were examined. Increased depressive activity was found in sera from nude mice and from mice recently treated with anti-thymocyte globulin, but no change was found in sera from thymectomized, irradiated, bone marrow-reconstituted mice, nor from lethally or sublethally irradiated or cyclophosphamide-treated mice. Base line DNA synthesis was, however, less inhibited by sera from irradiated or cyclophosphamide-treated mice. Increased depressive activity was found in sera from mice with graft-versus-host reaction and from mice injected with Salmonella enteritidis 11RX, in which macrophage stimulation occurred. Increased depressive activity was also found in the sera of mice injected with sheep erythrocytes. T cells do not appear to be a source of depressive activity but B cells, macrophages and nonlymphoid cells may be sources.", "contents": "Effect of sera from immunologically altered mice on phytohemagglutinin-induced mouse lymphocyte transformation. The DNA-synthetic response of mouse spleen cells to phytohemagglutinin in vitro is depressed by the addition of normal mouse serum. The effects of sera from mice that had been modified immunologically were examined. Increased depressive activity was found in sera from nude mice and from mice recently treated with anti-thymocyte globulin, but no change was found in sera from thymectomized, irradiated, bone marrow-reconstituted mice, nor from lethally or sublethally irradiated or cyclophosphamide-treated mice. Base line DNA synthesis was, however, less inhibited by sera from irradiated or cyclophosphamide-treated mice. Increased depressive activity was found in sera from mice with graft-versus-host reaction and from mice injected with Salmonella enteritidis 11RX, in which macrophage stimulation occurred. Increased depressive activity was also found in the sera of mice injected with sheep erythrocytes. T cells do not appear to be a source of depressive activity but B cells, macrophages and nonlymphoid cells may be sources."}
{"id": "PMID:13699", "title": "[Feeding and growth of elvers of anguilla Anguilla L. (eel-like teleosten fish) experimentally reared at various temperatures in the laboratory].", "content": "In France, there are few researches carried out on the eel's elvers rearing. So, we have undertaken to do, in a first time, a study of their alimentation and growth, in relation to the temperature, at laboratory. The structure of european eels' elvers population, drawn in its natural environment, shows a polymodal frequency distribution of individual weights. The temperature has a direct effect on general metabolism of animals and consequently on their growth. For temperatures included between 10 degrees C and 25 degrees C, any increase of this factor induced an individual activity more important. The quantity of ingested food and its rapidity of utilization, the precocity of alimentary behaviour, are in relation with temperature. The best growth is obtained at 25 degrees C. It seems that this temperature permits to have a very low mortality. From 10 degrees C and below, growth is inhibited, the individual activity and the alimentary taking are very low or non-existent. However, if temperature is elevated, from 11,5 degrees C, growth can start off again, animals are very active and an alimentary behavious is observed. At least, rearing of the european eels' elvers is possible with a salt water (salinity : 32 p. 1000); this system permits suppress in totality fungi desease (saprolegnia).", "contents": "[Feeding and growth of elvers of anguilla Anguilla L. (eel-like teleosten fish) experimentally reared at various temperatures in the laboratory]. In France, there are few researches carried out on the eel's elvers rearing. So, we have undertaken to do, in a first time, a study of their alimentation and growth, in relation to the temperature, at laboratory. The structure of european eels' elvers population, drawn in its natural environment, shows a polymodal frequency distribution of individual weights. The temperature has a direct effect on general metabolism of animals and consequently on their growth. For temperatures included between 10 degrees C and 25 degrees C, any increase of this factor induced an individual activity more important. The quantity of ingested food and its rapidity of utilization, the precocity of alimentary behaviour, are in relation with temperature. The best growth is obtained at 25 degrees C. It seems that this temperature permits to have a very low mortality. From 10 degrees C and below, growth is inhibited, the individual activity and the alimentary taking are very low or non-existent. However, if temperature is elevated, from 11,5 degrees C, growth can start off again, animals are very active and an alimentary behavious is observed. At least, rearing of the european eels' elvers is possible with a salt water (salinity : 32 p. 1000); this system permits suppress in totality fungi desease (saprolegnia)."}
{"id": "PMID:13702", "title": "Measurement of ionised calcium in body fluids-a review.", "content": "This paper reviews the techniques available to the clinical biochemist for measuring ionised calcium concentrations in biological fluids with particular reference to serum. At present ionised calcium may be measured colorimetrically, using tetramethyl murexide, or potentiometrically, using a calcium ion-selective electrode. These techniques compare favourably in terms of precision with existing methods for measuring total calcium. Advantages of measuring ionised calcium in preference to total calcium are (a) that there is no effect of venous occlusion or change of posture on the ionised fraction of the effect on total calcium, (b) that ionised calcium is the physiologically active form of the element, and (c) that the ionised calcium concentration is a more reliable indicator of the calcium status of patients in certain clinical conditions. The main problem in the measurement of ionised calcium is the marked dependence of the ionised fraction of the pH of the sample. Extreme care must be taken to avoid loss of CO2 or build-up of acid during the handling of the blood sample.", "contents": "Measurement of ionised calcium in body fluids-a review. This paper reviews the techniques available to the clinical biochemist for measuring ionised calcium concentrations in biological fluids with particular reference to serum. At present ionised calcium may be measured colorimetrically, using tetramethyl murexide, or potentiometrically, using a calcium ion-selective electrode. These techniques compare favourably in terms of precision with existing methods for measuring total calcium. Advantages of measuring ionised calcium in preference to total calcium are (a) that there is no effect of venous occlusion or change of posture on the ionised fraction of the effect on total calcium, (b) that ionised calcium is the physiologically active form of the element, and (c) that the ionised calcium concentration is a more reliable indicator of the calcium status of patients in certain clinical conditions. The main problem in the measurement of ionised calcium is the marked dependence of the ionised fraction of the pH of the sample. Extreme care must be taken to avoid loss of CO2 or build-up of acid during the handling of the blood sample."}
{"id": "PMID:13704", "title": "Comparative in vitro activity of piribenicillin, ticarcillin, and carbenicillin against Pseudomonas aeruginosa.", "content": "Pirbenicillin, a semisynthetic penicillin, showed greater in vitro activity against 68 recent isolates of Pseudomonas aeruginosa than did ticarcillin or carbenicillin. The median minimum inhibitory concentration of each of these three compounds, respectively, was 3.1, 12.5, and 25 mug/ml when a 10(-4) dilution of an overnight culture (about 10(5) colony-forming units [CFU]/ml) was used as inoculum, but these differences were less striking when larger inocula were used: at 10(7) CFU/ml these values were 6.25, 12.5, and 50 mug/ml, and at 10(8) to 10(9) CFU/ml these values were 50, 50, and 100 mug/ml. All three compounds showed greater inhibitory activity at pH 6 than at pH 8. This pH effect was greatest with pirbenicillin, for 6.25 mug of pirbenicillin per ml inhibited 7, 11, and 57% of the strains at pH 6, 7, and 8, respectively; these values were 4, 4, and 11% with ticarcillin and 0, 0, and 7% with carbenicillin. At sufficient inhibitory concentrations, the rates of bacterial killing of the three compounds were similar. The observed differences in anti-pseudomonad activity were not due to differences in stability to pseudomonad beta-lactamases, but all three compounds were more stable than were cefazolin, cephaloridine, and benzylpenicillin.", "contents": "Comparative in vitro activity of piribenicillin, ticarcillin, and carbenicillin against Pseudomonas aeruginosa. Pirbenicillin, a semisynthetic penicillin, showed greater in vitro activity against 68 recent isolates of Pseudomonas aeruginosa than did ticarcillin or carbenicillin. The median minimum inhibitory concentration of each of these three compounds, respectively, was 3.1, 12.5, and 25 mug/ml when a 10(-4) dilution of an overnight culture (about 10(5) colony-forming units [CFU]/ml) was used as inoculum, but these differences were less striking when larger inocula were used: at 10(7) CFU/ml these values were 6.25, 12.5, and 50 mug/ml, and at 10(8) to 10(9) CFU/ml these values were 50, 50, and 100 mug/ml. All three compounds showed greater inhibitory activity at pH 6 than at pH 8. This pH effect was greatest with pirbenicillin, for 6.25 mug of pirbenicillin per ml inhibited 7, 11, and 57% of the strains at pH 6, 7, and 8, respectively; these values were 4, 4, and 11% with ticarcillin and 0, 0, and 7% with carbenicillin. At sufficient inhibitory concentrations, the rates of bacterial killing of the three compounds were similar. The observed differences in anti-pseudomonad activity were not due to differences in stability to pseudomonad beta-lactamases, but all three compounds were more stable than were cefazolin, cephaloridine, and benzylpenicillin."}
{"id": "PMID:13705", "title": "Beta-Lactamase activity in strains of Bacteroides melaninogenicus and Bacteroides oralis.", "content": "beta-Lactamase from strains of Bacteroides melaninogenicus and Bacteroides oralis hydrolyzed penicillin more rapidly than ampicillin or carbenicillin. Cephalothin and a chromogenic cephalosporin (87/312) were also hydrolyzed by the enzyme. Activity was found only in beta-lactam-resistant strains, but there was considerable variation in activity among strains having the same minimal inhibitory concentrations of antibiotic. beta-Lactamase activity was cell bound and appeared to be tightly associated with the cell envelope since detergents were required to elute this activity.", "contents": "Beta-Lactamase activity in strains of Bacteroides melaninogenicus and Bacteroides oralis. beta-Lactamase from strains of Bacteroides melaninogenicus and Bacteroides oralis hydrolyzed penicillin more rapidly than ampicillin or carbenicillin. Cephalothin and a chromogenic cephalosporin (87/312) were also hydrolyzed by the enzyme. Activity was found only in beta-lactam-resistant strains, but there was considerable variation in activity among strains having the same minimal inhibitory concentrations of antibiotic. beta-Lactamase activity was cell bound and appeared to be tightly associated with the cell envelope since detergents were required to elute this activity."}
{"id": "PMID:13706", "title": "Purification and properties of an NADP+-specific isocitrate dehydrogenase from Rhizobium meliloti.", "content": "An NADP+-specific isocitrate dehydrogenase has been purified and characterized from Rhizobium meliloti. The enzyme showed Mn++ or Mg++ requirement. The apparent Km values were 2.00 x 10(-5) M and 1.51 x 10(-5) M for DL-isocitrate and NADP+, respectively. The enzyme was inhibited by ATP, to a lesser extent by ADP and AMP. alpha-Ketoglutarate also inhibited the enzyme activity. Oxalacetate and glyoxylate together inhibited the enzyme activity. The inhibition was competitive. Studies with thiol inhibitors suggested that the enzyme contained a sulfhydryl group at or near the active site. The enzyme has an approximate molecular weight of 60,000. Fluorescence studies suggested that the enzyme contained tryptophan.", "contents": "Purification and properties of an NADP+-specific isocitrate dehydrogenase from Rhizobium meliloti. An NADP+-specific isocitrate dehydrogenase has been purified and characterized from Rhizobium meliloti. The enzyme showed Mn++ or Mg++ requirement. The apparent Km values were 2.00 x 10(-5) M and 1.51 x 10(-5) M for DL-isocitrate and NADP+, respectively. The enzyme was inhibited by ATP, to a lesser extent by ADP and AMP. alpha-Ketoglutarate also inhibited the enzyme activity. Oxalacetate and glyoxylate together inhibited the enzyme activity. The inhibition was competitive. Studies with thiol inhibitors suggested that the enzyme contained a sulfhydryl group at or near the active site. The enzyme has an approximate molecular weight of 60,000. Fluorescence studies suggested that the enzyme contained tryptophan."}
{"id": "PMID:13703", "title": "Significance of gamma-glutamyl transferase (GGT) activity measurements in alcohol-induced hepatic injury.", "content": "Experimental evidence is presented that the determination of gamma-glutamyl transferase (GGT) activity in serum is useful in the assessment of alcohol-induced liver disease and for demonstrating to patients the toxic effects of their drinking habits on the liver. Serial measurements of GGT activity in serum have also proved valuable in monitoring the progress of therapy as well as alleged abstention from alcohol in the known alcoholic.", "contents": "Significance of gamma-glutamyl transferase (GGT) activity measurements in alcohol-induced hepatic injury. Experimental evidence is presented that the determination of gamma-glutamyl transferase (GGT) activity in serum is useful in the assessment of alcohol-induced liver disease and for demonstrating to patients the toxic effects of their drinking habits on the liver. Serial measurements of GGT activity in serum have also proved valuable in monitoring the progress of therapy as well as alleged abstention from alcohol in the known alcoholic."}
{"id": "PMID:13707", "title": "Mating reaction in Saccharomyces cerevisiae. X. Agglutinability-inactivating factor: a factor which destroys sexual agglutinability of a mating-type cells.", "content": "From cells of Saccharomyces cerevisiae a factor has been extracted that destroys the agglutinability of a mating-type cells specifically. It was found in the cell extracts of diploid and tetraploid strains as well as haploid strains of a and alpha mating types. It is heat-labile and the molecular weight is about 50,000. It is adsorbed by neither a cells nor alpha cells. Its biological activity is dependent on the incubation temperature and the pH, and is completely inhibited by phenylmethylsulfonyl fluoride, a potent inhibitor of the serine proteases. All the results described in this paper indicate that this factor is a proteolytic enzyme.", "contents": "Mating reaction in Saccharomyces cerevisiae. X. Agglutinability-inactivating factor: a factor which destroys sexual agglutinability of a mating-type cells. From cells of Saccharomyces cerevisiae a factor has been extracted that destroys the agglutinability of a mating-type cells specifically. It was found in the cell extracts of diploid and tetraploid strains as well as haploid strains of a and alpha mating types. It is heat-labile and the molecular weight is about 50,000. It is adsorbed by neither a cells nor alpha cells. Its biological activity is dependent on the incubation temperature and the pH, and is completely inhibited by phenylmethylsulfonyl fluoride, a potent inhibitor of the serine proteases. All the results described in this paper indicate that this factor is a proteolytic enzyme."}
{"id": "PMID:13709", "title": "Hydrolysis of lactose by immobilized microorganisms.", "content": "Cells of Lactobacillus bulgaricus, Escherichia coli, and Kluyveromyces (Saccharomyces) lactis immobilized in polyacrylamide gel beads retained 27 to 61% of the beta-galactosidase activity of intact cells. Optimum temperature and pH and thermostability of these microbial beta-galactosidases were negligibly affected by the immobilization. Km values of beta-galactosidase in immobilized cells of L. bulgaricus, E. coli, and K. lactis toward lactose were 4.2, 5.4, and 30 mM, respectively. Neither inhibition nor activation of beta-galactosidase in immobilized L. bulgaricus and E. coli appeared in the presence of galactose, but remarkable inhibition by galactose was detected in the case of the enzyme of immobilized K. lactis. Glucose inhibited noncompetitively the activity of three species of immobilized microbial cells. These kinetic properties were almost the same as those of free beta-galactosidase extracted from individual microorganisms. The activity of immobilized K. lactis was fairly stable during repeated runs, but those of E. coli and L. bulgaricus decreased gradually. These immobilized microbial cells, when introduced into skim milk, demonstrated high activity for converting lactose to monosaccharides. The flavor of skim milk was hardly affected by treatment with these immobilized cells, although the degree of sweetness was raised considerably.", "contents": "Hydrolysis of lactose by immobilized microorganisms. Cells of Lactobacillus bulgaricus, Escherichia coli, and Kluyveromyces (Saccharomyces) lactis immobilized in polyacrylamide gel beads retained 27 to 61% of the beta-galactosidase activity of intact cells. Optimum temperature and pH and thermostability of these microbial beta-galactosidases were negligibly affected by the immobilization. Km values of beta-galactosidase in immobilized cells of L. bulgaricus, E. coli, and K. lactis toward lactose were 4.2, 5.4, and 30 mM, respectively. Neither inhibition nor activation of beta-galactosidase in immobilized L. bulgaricus and E. coli appeared in the presence of galactose, but remarkable inhibition by galactose was detected in the case of the enzyme of immobilized K. lactis. Glucose inhibited noncompetitively the activity of three species of immobilized microbial cells. These kinetic properties were almost the same as those of free beta-galactosidase extracted from individual microorganisms. The activity of immobilized K. lactis was fairly stable during repeated runs, but those of E. coli and L. bulgaricus decreased gradually. These immobilized microbial cells, when introduced into skim milk, demonstrated high activity for converting lactose to monosaccharides. The flavor of skim milk was hardly affected by treatment with these immobilized cells, although the degree of sweetness was raised considerably."}
{"id": "PMID:13710", "title": "Deconjugation of bile acids by intestinal lactobacilli.", "content": "Lactobacillus species normally found in the intestinal tract of humans varied in the ability to deconjugate bile acids, whereas laboratory strains of Lactobacillus acidophilus deconjugated both glycocholate and taurocholate. All isolates of L. acidophilus from human feces deconjugated taurocholate, whereas only one of six deconjugated glycocholate. None of 13 isolates identified as L. casei deconjugated taurocholate, whereas 9 deconjugated glycocholate. The deconjugating system of L. acidophilus appeared to be constitutive, required low oxidation-reduction potential, and was most active at pH 6. No degradation beyond deconjugation was detected.", "contents": "Deconjugation of bile acids by intestinal lactobacilli. Lactobacillus species normally found in the intestinal tract of humans varied in the ability to deconjugate bile acids, whereas laboratory strains of Lactobacillus acidophilus deconjugated both glycocholate and taurocholate. All isolates of L. acidophilus from human feces deconjugated taurocholate, whereas only one of six deconjugated glycocholate. None of 13 isolates identified as L. casei deconjugated taurocholate, whereas 9 deconjugated glycocholate. The deconjugating system of L. acidophilus appeared to be constitutive, required low oxidation-reduction potential, and was most active at pH 6. No degradation beyond deconjugation was detected."}
{"id": "PMID:13711", "title": "Aggregation of poliovirus and reovirus by dilution in water.", "content": "Poliovirus and reovirus were found to aggregate into clumps of up to several hundred particles when diluted 10-fold into distilled water from a stock preparation of minimal aggregation in 0.05 M phosphate buffer, pH 7.2, plus 22 to 30% sucrose. Reovirus was also found to aggregate when diluted into phosphate-buffered saline. The aggregation was concentration dependent and did not occur when either virus was diluted into water 100-fold or greater. The aggregation of poliovirus was reversible by further addition of saline and produced a dispersed preparation of virus. Reovirus aggregation was not reversible. Both viruses aggregated when diluted into buffers at pH 5 and 3, and poliovirus aggregated at pH 6, and this aggregation of both viruses was reversible when returned to pH 7. Aggregation did not occur at alkaline pH values. Aggregation at low pH could be caused aggregation of either virus at pH 7. Calcium ions, however, were found to aggregate both viruses at a concentration of 0.01 M.", "contents": "Aggregation of poliovirus and reovirus by dilution in water. Poliovirus and reovirus were found to aggregate into clumps of up to several hundred particles when diluted 10-fold into distilled water from a stock preparation of minimal aggregation in 0.05 M phosphate buffer, pH 7.2, plus 22 to 30% sucrose. Reovirus was also found to aggregate when diluted into phosphate-buffered saline. The aggregation was concentration dependent and did not occur when either virus was diluted into water 100-fold or greater. The aggregation of poliovirus was reversible by further addition of saline and produced a dispersed preparation of virus. Reovirus aggregation was not reversible. Both viruses aggregated when diluted into buffers at pH 5 and 3, and poliovirus aggregated at pH 6, and this aggregation of both viruses was reversible when returned to pH 7. Aggregation did not occur at alkaline pH values. Aggregation at low pH could be caused aggregation of either virus at pH 7. Calcium ions, however, were found to aggregate both viruses at a concentration of 0.01 M."}
{"id": "PMID:13712", "title": "Ionic bonding, the mechanism of viral uptake by shellfish mucus.", "content": "An investigation was conducted to determine the processes involved in the contamination of shellfish by viruses. Results of binding-release studies show that the process involves the attachment of viruses to mucus secreted, and then ingested, by shellfish during feeding. Analysis of the mucus-virus bond involved selective degradation of the mucus and use of chemical agents to block carboxyl and sulfate groups on the mucus. Results obtained indicate that the attachment of virus to mucus is primarily ionic and involves the binding of viral particles to sulfate radicals on the mucopolysaccharide moiety of shellfish mucus.", "contents": "Ionic bonding, the mechanism of viral uptake by shellfish mucus. An investigation was conducted to determine the processes involved in the contamination of shellfish by viruses. Results of binding-release studies show that the process involves the attachment of viruses to mucus secreted, and then ingested, by shellfish during feeding. Analysis of the mucus-virus bond involved selective degradation of the mucus and use of chemical agents to block carboxyl and sulfate groups on the mucus. Results obtained indicate that the attachment of virus to mucus is primarily ionic and involves the binding of viral particles to sulfate radicals on the mucopolysaccharide moiety of shellfish mucus."}
{"id": "PMID:13713", "title": "Fermentation of L-aspartate by a saccharolytic strain of Bacteroides melaninogenicus.", "content": "Resting cells of Bacteroides melaninogenicus fermented L-[14C]aspartate as a single substrate. The 14C-labeled products included succinate, acetate, CO2, oxaloacetate, formate, malate, glycine, alanine, and fumarate in the relative percentages 68, 15, 9.9, 2.7, 1.8, 1.0, 0.7, 0.5, and 0.06, respectively, based on the total counts per minute of the L-[14C]aspartate fermented. Ammonia was produced in high amounts, indicating that 96% of the L-aspartate fermented was deaminated. These data suggest that L-aspartate is mainly being reduced through a number of intermediate reactions involving enzymes of the tricarboxylic acid cycle to succinate. L-[14C]asparagine was also fermented by resting cells of B. melaninogenicus to form L-aspartate, which was subsequently, but less actively, fermented.", "contents": "Fermentation of L-aspartate by a saccharolytic strain of Bacteroides melaninogenicus. Resting cells of Bacteroides melaninogenicus fermented L-[14C]aspartate as a single substrate. The 14C-labeled products included succinate, acetate, CO2, oxaloacetate, formate, malate, glycine, alanine, and fumarate in the relative percentages 68, 15, 9.9, 2.7, 1.8, 1.0, 0.7, 0.5, and 0.06, respectively, based on the total counts per minute of the L-[14C]aspartate fermented. Ammonia was produced in high amounts, indicating that 96% of the L-aspartate fermented was deaminated. These data suggest that L-aspartate is mainly being reduced through a number of intermediate reactions involving enzymes of the tricarboxylic acid cycle to succinate. L-[14C]asparagine was also fermented by resting cells of B. melaninogenicus to form L-aspartate, which was subsequently, but less actively, fermented."}
{"id": "PMID:13714", "title": "Sanitation in self-service automatic washers.", "content": "The potential for microbial transfer in self-service laundry washing machines was investigated by obtaining swab samples from the interior surfaces of commercial machines and wash water samples before and after disinfectant treatment. Three disinfectants (chlorine, a quaternary ammonium product, and a phenolic disinfectant) were used. Four self-service laundry facilities were sampled, with 10 replications of the procedure for each treatment at each location. Although washers were set on a warmwater setting, the wash water temperatures ranged from 24 to 51 degrees C. The quaternary ammonium product seemed most effective, averaging a 97% microbial kill; chlorine was the second most effective, with a 58% kill, and the phenolic disinfectant was least effective, with only a 25% kill. The efficacies of the chlorine and phenolic disinfectants were reduced at low water temperatures commonly experienced in self-service laundries. Interfamily cross-contamination in self-service facilities is a potential public health problem, which is aggravated by environmental conditions, such as water temperature and the practices of the previous users of the equipment. Procedural changes in laundering are recommended, including the use of a disinfectant to maintain adequate levels of sanitation.", "contents": "Sanitation in self-service automatic washers. The potential for microbial transfer in self-service laundry washing machines was investigated by obtaining swab samples from the interior surfaces of commercial machines and wash water samples before and after disinfectant treatment. Three disinfectants (chlorine, a quaternary ammonium product, and a phenolic disinfectant) were used. Four self-service laundry facilities were sampled, with 10 replications of the procedure for each treatment at each location. Although washers were set on a warmwater setting, the wash water temperatures ranged from 24 to 51 degrees C. The quaternary ammonium product seemed most effective, averaging a 97% microbial kill; chlorine was the second most effective, with a 58% kill, and the phenolic disinfectant was least effective, with only a 25% kill. The efficacies of the chlorine and phenolic disinfectants were reduced at low water temperatures commonly experienced in self-service laundries. Interfamily cross-contamination in self-service facilities is a potential public health problem, which is aggravated by environmental conditions, such as water temperature and the practices of the previous users of the equipment. Procedural changes in laundering are recommended, including the use of a disinfectant to maintain adequate levels of sanitation."}
{"id": "PMID:13739", "title": "Solar uticaria. Photoallergen in a patient's serum.", "content": "A 45-year-old man had solar urticaria that was activated by visible light. Passive transfer of the reactivity with the patient's serum to the skin of normal recipients was accomplished. Results of reverse passive transfer studies were negative. The patient developed an urticarial wheal at the site of injection of his own serum that had been previously exposed to light in vitro. The experimental data suggested that his condition was attributable to an allergic response. Systemic administration of reserpine was of some therapeutic value, and increasing exposure to natural sunlight was associated with substantial in crease in his tolerance to sunlight. Unfortunately, the possible loss of reactivity that may occur in the natural course of the disease makes substantiation of the therapeutic effects difficult.", "contents": "Solar uticaria. Photoallergen in a patient's serum. A 45-year-old man had solar urticaria that was activated by visible light. Passive transfer of the reactivity with the patient's serum to the skin of normal recipients was accomplished. Results of reverse passive transfer studies were negative. The patient developed an urticarial wheal at the site of injection of his own serum that had been previously exposed to light in vitro. The experimental data suggested that his condition was attributable to an allergic response. Systemic administration of reserpine was of some therapeutic value, and increasing exposure to natural sunlight was associated with substantial in crease in his tolerance to sunlight. Unfortunately, the possible loss of reactivity that may occur in the natural course of the disease makes substantiation of the therapeutic effects difficult."}
{"id": "PMID:13740", "title": "Some aspects of the persistence and fate of acrolein herbicide in water.", "content": "Experimental data for the decay of acrolein approximated first order kinetics. The reaction continued to completion in local waters but in buffered solution (pH 5.1-8.6) an equilibrium was reached after reaction of about 92% of the acrolein. It is proposed that data presented on the effects of pH on decay of acrolein may be used as a conservative estimate of dissipation rates in water where non-target organisms are at risk. In flowing water in two channels the 8 to 10 fold discrepancy between observed and predicted rates of dissipation was attributed to major losses in volatilization and adsorption. A relatively non-volatile reaction product (which gave a positive reaction with dinitrophenylhydrazine) accumulated initially but dissipated rapidly, probably by microbiological processes, when acrolein concentrations fell below about 2 to 3 ppm.", "contents": "Some aspects of the persistence and fate of acrolein herbicide in water. Experimental data for the decay of acrolein approximated first order kinetics. The reaction continued to completion in local waters but in buffered solution (pH 5.1-8.6) an equilibrium was reached after reaction of about 92% of the acrolein. It is proposed that data presented on the effects of pH on decay of acrolein may be used as a conservative estimate of dissipation rates in water where non-target organisms are at risk. In flowing water in two channels the 8 to 10 fold discrepancy between observed and predicted rates of dissipation was attributed to major losses in volatilization and adsorption. A relatively non-volatile reaction product (which gave a positive reaction with dinitrophenylhydrazine) accumulated initially but dissipated rapidly, probably by microbiological processes, when acrolein concentrations fell below about 2 to 3 ppm."}
{"id": "PMID:13741", "title": "[Bacteriological examination of sputum (author's transl)].", "content": "The AA., emphasizing the importance of ascertain the bronchial source of microorganisms recoverable from sputum, recommend for this purpose the use of properly collected sputum specimens and the application of washing treatment for mucopurulent materials. The aim of the present study has been to verify the effectiveness of mechanical apparatus to homogenize sputum without affecting the viability of resident microorganisms and the usefulness of prior microscopical examination to establish the rate of dilute inocula for the culture.", "contents": "[Bacteriological examination of sputum (author's transl)]. The AA., emphasizing the importance of ascertain the bronchial source of microorganisms recoverable from sputum, recommend for this purpose the use of properly collected sputum specimens and the application of washing treatment for mucopurulent materials. The aim of the present study has been to verify the effectiveness of mechanical apparatus to homogenize sputum without affecting the viability of resident microorganisms and the usefulness of prior microscopical examination to establish the rate of dilute inocula for the culture."}
{"id": "PMID:13742", "title": "[Study on the viscolytic activity of the sputum (author's transl)].", "content": "Several mucolytic agents were evaluated on sputum for testing their viscolytic activity and the bacterial tollerance to each of them. Proteolytic enzymes (trypsin, pepsin, papain, pancreatin), KJ, and dithiothreitol (or its derivatives) were better tollerated by common respiratory pathogens (H. influenzae, D. pneumoniae, Klebsiella, etc.) than other mucolytic agents, as acetil-cysteine, cisteamine-HCl, tension active substances, mercaptoethanol, and others. The dithiothreitol showed also one of the strongest viscolytic effect and therefore it was selected for the routinary sputum digestion at the concentration 0.1% in PBS pH 7.2. Such a solution was added to sputum specimen in different proportions according to the macroscopic \"apparent\" viscosity of each specimen. However researches on the comparative viscolytic activity of all the agents hereinafter considered are still in progress.", "contents": "[Study on the viscolytic activity of the sputum (author's transl)]. Several mucolytic agents were evaluated on sputum for testing their viscolytic activity and the bacterial tollerance to each of them. Proteolytic enzymes (trypsin, pepsin, papain, pancreatin), KJ, and dithiothreitol (or its derivatives) were better tollerated by common respiratory pathogens (H. influenzae, D. pneumoniae, Klebsiella, etc.) than other mucolytic agents, as acetil-cysteine, cisteamine-HCl, tension active substances, mercaptoethanol, and others. The dithiothreitol showed also one of the strongest viscolytic effect and therefore it was selected for the routinary sputum digestion at the concentration 0.1% in PBS pH 7.2. Such a solution was added to sputum specimen in different proportions according to the macroscopic \"apparent\" viscosity of each specimen. However researches on the comparative viscolytic activity of all the agents hereinafter considered are still in progress."}
{"id": "PMID:13743", "title": "[Aerobic flora examination of sputum (author's transl)].", "content": "The routine bacteriological test of expectorate, except for mycobacteria, is usually unsatisfactory. There is a need of standardization which results in the present paper from a comparison between the data obtained by two different laboratories on the same samples. It is possible to achieve reasonable and uniform results establishing a uniformity of some procedures, namely; collection of specimens, homogenization, number and type of media, interpretation of data and so on.", "contents": "[Aerobic flora examination of sputum (author's transl)]. The routine bacteriological test of expectorate, except for mycobacteria, is usually unsatisfactory. There is a need of standardization which results in the present paper from a comparison between the data obtained by two different laboratories on the same samples. It is possible to achieve reasonable and uniform results establishing a uniformity of some procedures, namely; collection of specimens, homogenization, number and type of media, interpretation of data and so on."}
{"id": "PMID:13744", "title": "[Resistance to antibiotics of bacteria involved in respiratory infections (author's transl)].", "content": "The present status of resistance to antibiotics of bacteria involved in respiratory infections is reviewed. Schematically it can outlined as follows. Streptococcus B-haemolyticus as well as Pneumococcus did not change their sensitivity to penicillin, but some strains are now resistant to tetracycline. Streptococcus viridans, Enterococcus and H. influenzae did not change substantially their sensitivity to antibiotics. Staphylococcus aureus is the bacterial species that always poses some problems with regard to antibiotic resistance. Due to the selection of strains penicillinase-producing because of the large use of penicillin, the most part of clinical isolates of staphylococci is now resistant to penicillin. In addition an increased number of strains resistant to the other antibiotics has been registered as soon as they has been introduced in therapy. The resistant strains spread in a particularly rapid way in hospital. The introduction in therapy of penicillinase-resistant penicillins constituted a remarkable advance in therapy of staphylococcal infection. However, there is now a growing number of indications about the emergence of methicillin resistant strains of staphylococci. On the other hand it must be recalled that since 1960 a marked reduction of incidence and mortality in severe staphylococcal infections has been noted. Incidence and mortality of respiratory infections due to Gram-negative bacilli is augmented particularly in connection with a larger use of immunosuppressive and antineoplastic therapies, of particular surgical or reanimation procedures, of intensive courses of antibiotic therapy etc. Emergence of Pseudomonas, Proteus, Serratia, Providencia, etc. infections poses many difficult problems of chemotherapy since these species are scarcely sensitive to antibiotics. Carbenicillin, cephalosporins, sisomicin, tobramycin, amikacin are the more recent drugs that alone or in combination may offer some chances of success in this field.", "contents": "[Resistance to antibiotics of bacteria involved in respiratory infections (author's transl)]. The present status of resistance to antibiotics of bacteria involved in respiratory infections is reviewed. Schematically it can outlined as follows. Streptococcus B-haemolyticus as well as Pneumococcus did not change their sensitivity to penicillin, but some strains are now resistant to tetracycline. Streptococcus viridans, Enterococcus and H. influenzae did not change substantially their sensitivity to antibiotics. Staphylococcus aureus is the bacterial species that always poses some problems with regard to antibiotic resistance. Due to the selection of strains penicillinase-producing because of the large use of penicillin, the most part of clinical isolates of staphylococci is now resistant to penicillin. In addition an increased number of strains resistant to the other antibiotics has been registered as soon as they has been introduced in therapy. The resistant strains spread in a particularly rapid way in hospital. The introduction in therapy of penicillinase-resistant penicillins constituted a remarkable advance in therapy of staphylococcal infection. However, there is now a growing number of indications about the emergence of methicillin resistant strains of staphylococci. On the other hand it must be recalled that since 1960 a marked reduction of incidence and mortality in severe staphylococcal infections has been noted. Incidence and mortality of respiratory infections due to Gram-negative bacilli is augmented particularly in connection with a larger use of immunosuppressive and antineoplastic therapies, of particular surgical or reanimation procedures, of intensive courses of antibiotic therapy etc. Emergence of Pseudomonas, Proteus, Serratia, Providencia, etc. infections poses many difficult problems of chemotherapy since these species are scarcely sensitive to antibiotics. Carbenicillin, cephalosporins, sisomicin, tobramycin, amikacin are the more recent drugs that alone or in combination may offer some chances of success in this field."}
{"id": "PMID:13746", "title": "Treatment of hemorrhagic gastritis by antacid.", "content": "A simple and safe method of nonsurgical treatment for the control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrocloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleeding had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89% control of hemorrhage compare favorably with those in the literature.", "contents": "Treatment of hemorrhagic gastritis by antacid. A simple and safe method of nonsurgical treatment for the control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrocloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleeding had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89% control of hemorrhage compare favorably with those in the literature."}
{"id": "PMID:13747", "title": "Patterns of gastroesophageal reflux in health and disease.", "content": "Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor.", "contents": "Patterns of gastroesophageal reflux in health and disease. Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor."}
{"id": "PMID:13748", "title": "Long-term follow-up of internal mammary artery myocardial implantation.", "content": "A study was made of 100 patients who had undergone internal mammary artery myocardial implantation 7 to 10 years previously. Forty-two patients had single implantation with or without a free omental graft, and 54 received double implantations. Four patients had a single internal mammary artery implant plus a single aortocoronary bypass graft. Eleven patients died at operation or within the first month, and 17 died from 1 to 7 years following operation. Two were lost to follow-up, and 15 refused follow-up angiograms. From 7 to 10 years postoperatively, angiographic studies were performed on 55 patients with 73 internal mammary artery implants. Of these 73 implants, 17 (23%) were occluded; 10 (14%) were patent but did not show myocardial filling; 15 (21%) showed myocardial blush or filling of small vessels; and 31 (42%) showed filling of a major coronary artery. The patency rate correlated well with the amount of coronary disease and slightly with the amount of symptomatic improvement. This study shows that the Vineberg operation is physiologically sound; however, the ideal candidates are those patients with coronary arteries of adequate size who could benefit more by direct perfusion.", "contents": "Long-term follow-up of internal mammary artery myocardial implantation. A study was made of 100 patients who had undergone internal mammary artery myocardial implantation 7 to 10 years previously. Forty-two patients had single implantation with or without a free omental graft, and 54 received double implantations. Four patients had a single internal mammary artery implant plus a single aortocoronary bypass graft. Eleven patients died at operation or within the first month, and 17 died from 1 to 7 years following operation. Two were lost to follow-up, and 15 refused follow-up angiograms. From 7 to 10 years postoperatively, angiographic studies were performed on 55 patients with 73 internal mammary artery implants. Of these 73 implants, 17 (23%) were occluded; 10 (14%) were patent but did not show myocardial filling; 15 (21%) showed myocardial blush or filling of small vessels; and 31 (42%) showed filling of a major coronary artery. The patency rate correlated well with the amount of coronary disease and slightly with the amount of symptomatic improvement. This study shows that the Vineberg operation is physiologically sound; however, the ideal candidates are those patients with coronary arteries of adequate size who could benefit more by direct perfusion."}
{"id": "PMID:13749", "title": "Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs.", "content": "The existence of a relationship between inhibition of prostaglandin biosynthesis and analgesic or anti-inflammatory activity was investigated in the case of the non-narcotic analgesics glafenine, floctafenine and clometacine, in comparison to indomethacin and acetylsalicylic acid. These compounds inhibit prostaglandin biosynthesis from arachidonic acid in a guinea-pig lung homogenate as strongly as indomethacin. On its biosynthesis in rat epididymal tissue stimulated by noradrenaline, glafenine equals indomethacin inhibitory potency, whereas floctafenine and clometacine are less active. Acetylsalicylic acid is the least active in both preparations. In vivo, prostaglandin biosynthesis induced in rat peritoneal fluid by injection of acetic acid is inhibited by the 5 drugs, ranked as follows: floctafenine greater than indomethacin greater than glafenine greater than clometacine greater than acetylsalicylic acid. The pharmacological profile of glafenine, floctafenine and clometacine is characterized by a relatively strong effect on acetic acid writhing and a relatively weak effect on carrageenin oedema, U.V. erythema and adjuvant arthritis. The inhibition of prostaglandin biosynthesis seems better correlated with their analgesic activity than with their anti-inflammatory effects. The results show that prostaglandins could play an important role in the genesis of tissulary pain in animals.", "contents": "Inhibition of prostaglandin biosynthesis by non-narcotic analgesic drugs. The existence of a relationship between inhibition of prostaglandin biosynthesis and analgesic or anti-inflammatory activity was investigated in the case of the non-narcotic analgesics glafenine, floctafenine and clometacine, in comparison to indomethacin and acetylsalicylic acid. These compounds inhibit prostaglandin biosynthesis from arachidonic acid in a guinea-pig lung homogenate as strongly as indomethacin. On its biosynthesis in rat epididymal tissue stimulated by noradrenaline, glafenine equals indomethacin inhibitory potency, whereas floctafenine and clometacine are less active. Acetylsalicylic acid is the least active in both preparations. In vivo, prostaglandin biosynthesis induced in rat peritoneal fluid by injection of acetic acid is inhibited by the 5 drugs, ranked as follows: floctafenine greater than indomethacin greater than glafenine greater than clometacine greater than acetylsalicylic acid. The pharmacological profile of glafenine, floctafenine and clometacine is characterized by a relatively strong effect on acetic acid writhing and a relatively weak effect on carrageenin oedema, U.V. erythema and adjuvant arthritis. The inhibition of prostaglandin biosynthesis seems better correlated with their analgesic activity than with their anti-inflammatory effects. The results show that prostaglandins could play an important role in the genesis of tissulary pain in animals."}
{"id": "PMID:13750", "title": "Selectivity of clenbuterol (NAB 365) in guinea-pig isolated tissues containing beta-adrenoceptors.", "content": "The effects of clenbuterol (ANB 365), an aminohalogen substituted phenylethanolamine, have been examined on isolated tissue preparations from guinea-pigs. Clenbuterol produced concentration (or dose)-dependent relaxations of tracheal chains, decreases in perfusion pressure of hind limb blood vessels, inhibitions of acetylcholine-induced contractions of the uterus, increases in atrial rate and inhibitions of electrically-induced contractions of the ileum. These responses were blocked by propranolol. Clenbuterol was similar in potency to isoprenaline on the trachea (carbachol-contracted), hind limb and uterus (beta2-adrenoceptors) but was significantly less potent than isoprenaline on the atria and the ileum (beta1-adrenoceptors). Clenbuterol produced marked relaxation of intrinsic tone tracheal preparations in concentrations up to 3000 times less than were required on carbachol-contracted preparations, whereas for isoprenaline the concentrations required on intrinsic tone preparations were only 55 fold less. It is concluded that clenbuterol is a beta-adrenoceptor agonist and that it is a partial agonist on the carbachol-stimulated trachea, on the atria and on hind limb blood vessels. It shows beta2-selectivity in that its potency, relative to that of isoprenaline, on the preparations containing beta2-adrenoceptors was much higher than on those with beta1-adrenoceptors. On intrinsic tone tracheal preparations it may produce an additional relaxant effect responsible for its high potency on that preparation.", "contents": "Selectivity of clenbuterol (NAB 365) in guinea-pig isolated tissues containing beta-adrenoceptors. The effects of clenbuterol (ANB 365), an aminohalogen substituted phenylethanolamine, have been examined on isolated tissue preparations from guinea-pigs. Clenbuterol produced concentration (or dose)-dependent relaxations of tracheal chains, decreases in perfusion pressure of hind limb blood vessels, inhibitions of acetylcholine-induced contractions of the uterus, increases in atrial rate and inhibitions of electrically-induced contractions of the ileum. These responses were blocked by propranolol. Clenbuterol was similar in potency to isoprenaline on the trachea (carbachol-contracted), hind limb and uterus (beta2-adrenoceptors) but was significantly less potent than isoprenaline on the atria and the ileum (beta1-adrenoceptors). Clenbuterol produced marked relaxation of intrinsic tone tracheal preparations in concentrations up to 3000 times less than were required on carbachol-contracted preparations, whereas for isoprenaline the concentrations required on intrinsic tone preparations were only 55 fold less. It is concluded that clenbuterol is a beta-adrenoceptor agonist and that it is a partial agonist on the carbachol-stimulated trachea, on the atria and on hind limb blood vessels. It shows beta2-selectivity in that its potency, relative to that of isoprenaline, on the preparations containing beta2-adrenoceptors was much higher than on those with beta1-adrenoceptors. On intrinsic tone tracheal preparations it may produce an additional relaxant effect responsible for its high potency on that preparation."}
{"id": "PMID:13751", "title": "Serum corticosterone as a quantitative test of the phlogistic potency of various agents topically applied in the rat.", "content": "The application into the rat conjunctiva of various phlogistic agents, such as croton oil, mustard oil and formaldehyde, elicits an increase of serum corticosterone linearly related to the log of the applied concentrations, so that from their parallelized regression lines it is possible to calculate the phlogistic potency of each tested agent in reference to croton oil. The time kinetic of such an increase (elicited by croton oil) is compared with that of two other parameters previously adopted as indirect quantitative indices of the phlogosis: the adrenal ascorbic acid depletion and the liver tyrosine-alpha-ketoglutarate transaminase increase. Serum corticosterone is shown to be the quickest and the most sensitive of the adopted indices, even if the phlogistic potency of the tested agents and the precision of these evaluations substantially coincides whatsoever the index adopted. Finally the pathways of adrenocortical activation are investigated and it is shown that the activation may be peripherally blocked by topical application of corticosteroids (but not of local anesthetics) and centrally by hypophysectomy or parenteral administration of pentobarbital plus morphine.", "contents": "Serum corticosterone as a quantitative test of the phlogistic potency of various agents topically applied in the rat. The application into the rat conjunctiva of various phlogistic agents, such as croton oil, mustard oil and formaldehyde, elicits an increase of serum corticosterone linearly related to the log of the applied concentrations, so that from their parallelized regression lines it is possible to calculate the phlogistic potency of each tested agent in reference to croton oil. The time kinetic of such an increase (elicited by croton oil) is compared with that of two other parameters previously adopted as indirect quantitative indices of the phlogosis: the adrenal ascorbic acid depletion and the liver tyrosine-alpha-ketoglutarate transaminase increase. Serum corticosterone is shown to be the quickest and the most sensitive of the adopted indices, even if the phlogistic potency of the tested agents and the precision of these evaluations substantially coincides whatsoever the index adopted. Finally the pathways of adrenocortical activation are investigated and it is shown that the activation may be peripherally blocked by topical application of corticosteroids (but not of local anesthetics) and centrally by hypophysectomy or parenteral administration of pentobarbital plus morphine."}
{"id": "PMID:13753", "title": "Photoproduction of ammonium ion from N2 in Rhodospirillum rubrum.", "content": "NH+4 excretion was undetectable in N2-fixing cultures of Rhodospirillum rubrum (S-1) and nitrogenase activity in these cultures was repressed by the addition of 10 mM NH+4 to the medium. The glutamate analog, L-methionine-DL-sulfoximine (MSX), derepressed N2 fixation even in the presence of 10 mM extracellular NH+4. When 10 mg MSX/ml was added to cultures just prior to nitrogenase induction they developed nitrogenase activity (20% of the control activities) and excreted most of their fixed N2 as NH+4. Nitrogenase activities and NH+4 production from fixed N2 were increased considerably when a combined nitrogen source, NH+4 (greater than 40 mumoles NH+4/mg cell protein in 6 days) or L-glutamate (greater than 60 mumoles NH+4/ mg cell protein in 6 days) was added to the cultures together with MSX. Biochemical analysis revealed that R. rubrum produced glutamine synthetase and glutamate synthase (NADP-dependent) but no detectable NADP-dependent glutamate dehydrogenase. The specific activity of glutamine synthetase was observed to be maximal when nitrogenase activity was also maximal. Nitrogenase and glutamine synthetase activities were repressed by NH+4 as well as by glutamate. The results demonstrate that utilization of solar energy to photoproduce large quantities of NH+4 from N2 is possible with photosynthetic bacteria by interfering with their regulatory control of N2 fixation.", "contents": "Photoproduction of ammonium ion from N2 in Rhodospirillum rubrum. NH+4 excretion was undetectable in N2-fixing cultures of Rhodospirillum rubrum (S-1) and nitrogenase activity in these cultures was repressed by the addition of 10 mM NH+4 to the medium. The glutamate analog, L-methionine-DL-sulfoximine (MSX), derepressed N2 fixation even in the presence of 10 mM extracellular NH+4. When 10 mg MSX/ml was added to cultures just prior to nitrogenase induction they developed nitrogenase activity (20% of the control activities) and excreted most of their fixed N2 as NH+4. Nitrogenase activities and NH+4 production from fixed N2 were increased considerably when a combined nitrogen source, NH+4 (greater than 40 mumoles NH+4/mg cell protein in 6 days) or L-glutamate (greater than 60 mumoles NH+4/ mg cell protein in 6 days) was added to the cultures together with MSX. Biochemical analysis revealed that R. rubrum produced glutamine synthetase and glutamate synthase (NADP-dependent) but no detectable NADP-dependent glutamate dehydrogenase. The specific activity of glutamine synthetase was observed to be maximal when nitrogenase activity was also maximal. Nitrogenase and glutamine synthetase activities were repressed by NH+4 as well as by glutamate. The results demonstrate that utilization of solar energy to photoproduce large quantities of NH+4 from N2 is possible with photosynthetic bacteria by interfering with their regulatory control of N2 fixation."}
{"id": "PMID:13754", "title": "Energy coupling and respiration in Nitrosomonas europaea.", "content": "Intact cells of Nitrosomonas europaea grown in an ammonium salts medium will oxidise ammonium ions, hydroxylamine and ascorbate-TMPD; there is no oxidation of carbon monoxide, methane or methanol. The Km value for ammonia oxidation is highly pH dependent with a minimum value of 0.5 mM above pH 8.0. This suggests that free ammonia is the species crossing the cytoplasmic membrane(s). The measurement of respiration driven proton translocation indicates that there is probably only one proton translocating loop (loop 3) association with hydroxylamine oxidation. The oxidation of \"endogenous\" substrates is sometimes associated with more than one proton-translocating loop. These results indicate that during growth hydroxylamine oxidation is probably associated with a maximum P/O ratio of 1.", "contents": "Energy coupling and respiration in Nitrosomonas europaea. Intact cells of Nitrosomonas europaea grown in an ammonium salts medium will oxidise ammonium ions, hydroxylamine and ascorbate-TMPD; there is no oxidation of carbon monoxide, methane or methanol. The Km value for ammonia oxidation is highly pH dependent with a minimum value of 0.5 mM above pH 8.0. This suggests that free ammonia is the species crossing the cytoplasmic membrane(s). The measurement of respiration driven proton translocation indicates that there is probably only one proton translocating loop (loop 3) association with hydroxylamine oxidation. The oxidation of \"endogenous\" substrates is sometimes associated with more than one proton-translocating loop. These results indicate that during growth hydroxylamine oxidation is probably associated with a maximum P/O ratio of 1."}
{"id": "PMID:13755", "title": "D-Alanine dehydrogenase. Its role in the utilisation of alanine isomers as growth substrates by Pseudomonas aeruginosa PA01.", "content": "Pseudomonas aeruginosa PA01 was found to utilise both the D- and L-isomers of alpha-alanine and also beta-alanine as sole sources of carbon and energy for growth. Enzymological studies of wild-type cultures and comparison with mutants deficient in growth upon one or more isomers of alanine led to the following conclusions: (i) utilisation of D-alanine involved its direct oxidation by an inducible, membrane-bound, cytochrome-linked dehydrogenase; (ii) utilisation of L-alanine required its conversion to the directly oxidisable D-form by a soluble racemase; (iii) utilisation of beta-alanine, like L-alanine, involves both the racemase and D-alanine dehydrogenase enzymes, but in addition must involve other enzymes the identity of which is still speculative; (iv) P. aeruginosa, like Escherichia coli, appears to take up D-alanine and L-alanine by means of two specific permeases.", "contents": "D-Alanine dehydrogenase. Its role in the utilisation of alanine isomers as growth substrates by Pseudomonas aeruginosa PA01. Pseudomonas aeruginosa PA01 was found to utilise both the D- and L-isomers of alpha-alanine and also beta-alanine as sole sources of carbon and energy for growth. Enzymological studies of wild-type cultures and comparison with mutants deficient in growth upon one or more isomers of alanine led to the following conclusions: (i) utilisation of D-alanine involved its direct oxidation by an inducible, membrane-bound, cytochrome-linked dehydrogenase; (ii) utilisation of L-alanine required its conversion to the directly oxidisable D-form by a soluble racemase; (iii) utilisation of beta-alanine, like L-alanine, involves both the racemase and D-alanine dehydrogenase enzymes, but in addition must involve other enzymes the identity of which is still speculative; (iv) P. aeruginosa, like Escherichia coli, appears to take up D-alanine and L-alanine by means of two specific permeases."}
{"id": "PMID:13756", "title": "Monosaccharide transport systems in the yeast Rhodotorula glutinis.", "content": "By using D-glucose, D-xylose, D-galactose and D-fructose in the strictly aerobic yeast Rhodotorula glutinis and by comparing the half-saturation constants with inhibition constants the yeast was shown to possess a single common system for D-xylose and D-galactose (Km's and Ki's all between 0.5 and 1.1 mM) but another distinct transport system for D-fructose. The transport of D-glucose has a special position in that glucose blocks apparently allotopically all the other systems observed although it uses at least one of them for its own transport. The different character of D-glucose uptake is underlined by its relative independence of pH (its \"Km\" is completely pH-insensitive) in contrast with all other sugars. At low concentrations, all sugars show mutual positive cooperativity in uptake, suggesting at least two transport sites plus possibly a modifier site on the carrier.", "contents": "Monosaccharide transport systems in the yeast Rhodotorula glutinis. By using D-glucose, D-xylose, D-galactose and D-fructose in the strictly aerobic yeast Rhodotorula glutinis and by comparing the half-saturation constants with inhibition constants the yeast was shown to possess a single common system for D-xylose and D-galactose (Km's and Ki's all between 0.5 and 1.1 mM) but another distinct transport system for D-fructose. The transport of D-glucose has a special position in that glucose blocks apparently allotopically all the other systems observed although it uses at least one of them for its own transport. The different character of D-glucose uptake is underlined by its relative independence of pH (its \"Km\" is completely pH-insensitive) in contrast with all other sugars. At low concentrations, all sugars show mutual positive cooperativity in uptake, suggesting at least two transport sites plus possibly a modifier site on the carrier."}
{"id": "PMID:13757", "title": "Energetic aspects of anaerobic growth of Aerobacter aerogenes in complex medium.", "content": "Molar growth yields for anaerobic growth of Aerobacter aerogenes in complex medium were much higher than for growth in minimal medium. In batch cultures the molar growth yield for glucose varied from 44 to 50 and YATP from 17.1 to 18.8. For glucose-limited chemostat cultures a value of 17.5 g/mole was found for Y max ATP and a value of 2.3 mmoles ATP/g dry weight h for the maintenance coeficient. Growth-dependent pH changes were used to control the addition of fresh medium, containing excess of glucose to a continuous culture. The specific growth rate and the population density were dependent on the pH difference between the inflowing medium and the culture. At a mu value of 1.44 h-1 the molar growth yield for glucose was about 70 and Y ATP about 28.5. An equation is presented, which gives the relation between theoretical and experimental Y max ATP values.", "contents": "Energetic aspects of anaerobic growth of Aerobacter aerogenes in complex medium. Molar growth yields for anaerobic growth of Aerobacter aerogenes in complex medium were much higher than for growth in minimal medium. In batch cultures the molar growth yield for glucose varied from 44 to 50 and YATP from 17.1 to 18.8. For glucose-limited chemostat cultures a value of 17.5 g/mole was found for Y max ATP and a value of 2.3 mmoles ATP/g dry weight h for the maintenance coeficient. Growth-dependent pH changes were used to control the addition of fresh medium, containing excess of glucose to a continuous culture. The specific growth rate and the population density were dependent on the pH difference between the inflowing medium and the culture. At a mu value of 1.44 h-1 the molar growth yield for glucose was about 70 and Y ATP about 28.5. An equation is presented, which gives the relation between theoretical and experimental Y max ATP values."}
{"id": "PMID:13758", "title": "Proton-motive force and the motile behavior of Bacillus subtilis.", "content": "Changes in the proton-motive force cause a transient change in the motile behavior of Bacillus subtilis cells. Both an increase and a decrease in the proton-motive force caused transient tumbling. Simultaneous decrease of proton-motive force and increase of attractant concentration lessens the response toward the attractant. A simultaneous increase of proton-motive force and increase of attractant concentration prolonges the response toward attractant. A hypothesis explaining the various effects is given.", "contents": "Proton-motive force and the motile behavior of Bacillus subtilis. Changes in the proton-motive force cause a transient change in the motile behavior of Bacillus subtilis cells. Both an increase and a decrease in the proton-motive force caused transient tumbling. Simultaneous decrease of proton-motive force and increase of attractant concentration lessens the response toward the attractant. A simultaneous increase of proton-motive force and increase of attractant concentration prolonges the response toward attractant. A hypothesis explaining the various effects is given."}
{"id": "PMID:13759", "title": "Ammonium uptake and metabolism by mitrogen fixing bacteria. II. Klebsiella pneumoniae.", "content": "The primary steps of N2, ammonia and nitrate metabolism in Klebsiella pneumoniae grown in a continuous culture are regulated by the kind and supply of the nitrogenous compound. Cultures growing on N2 as the only nitrogen source have high activities of nitrogenase, unadenylated glutamine synthetase and glutamate synthase and low levels of glutamate dehydrogenase. If small amounts of ammonium salts are added continuously, initially only part of it is absorbed by the organisms. After 2-3 h complete absorption of ammonia against an ammonium gradient coinciding with an increased growth rate of the bacteria is observed. The change in the extracellular ammonium level is paralleled by the intracellular glutamine concentration which in turn regulates the glutamine synthesis and an induction of glutamate dehydrogenase synthesis. Upon deadenylation these events are reversed.--Addition of dinitrophenol causes transient leakage of intracellular ammonium into the medium.", "contents": "Ammonium uptake and metabolism by mitrogen fixing bacteria. II. Klebsiella pneumoniae. The primary steps of N2, ammonia and nitrate metabolism in Klebsiella pneumoniae grown in a continuous culture are regulated by the kind and supply of the nitrogenous compound. Cultures growing on N2 as the only nitrogen source have high activities of nitrogenase, unadenylated glutamine synthetase and glutamate synthase and low levels of glutamate dehydrogenase. If small amounts of ammonium salts are added continuously, initially only part of it is absorbed by the organisms. After 2-3 h complete absorption of ammonia against an ammonium gradient coinciding with an increased growth rate of the bacteria is observed. The change in the extracellular ammonium level is paralleled by the intracellular glutamine concentration which in turn regulates the glutamine synthesis and an induction of glutamate dehydrogenase synthesis. Upon deadenylation these events are reversed.--Addition of dinitrophenol causes transient leakage of intracellular ammonium into the medium."}
{"id": "PMID:13760", "title": "Ammonia assimilation in the fission yeast Schizosaccharomyces pombe 972.", "content": "Glutamine synthetase (GS) activity of Schizosaccharomyces pombe 972 was high in ammonia-limited cultures, low in phosphate- and sulphate-limited cultures and not detected in glucose-limited cultures. When ammonia was 'pulsed' into an ammonia-limited culture then GS activity decreased at a rate faster than that calculated if enzyme synthesis ceased and enzyme was diluted out by growth. Enzyme activity increased in ammonia-starved, phosphate-limited cultures and in the ammonia 'pulse' system when the added ammonia had been utilised. These increases in enzyme activity were prevented by the presence of 100 mug/ml cycloheximide. GS activity was inversely related to the intracellular concentration of glutamate.", "contents": "Ammonia assimilation in the fission yeast Schizosaccharomyces pombe 972. Glutamine synthetase (GS) activity of Schizosaccharomyces pombe 972 was high in ammonia-limited cultures, low in phosphate- and sulphate-limited cultures and not detected in glucose-limited cultures. When ammonia was 'pulsed' into an ammonia-limited culture then GS activity decreased at a rate faster than that calculated if enzyme synthesis ceased and enzyme was diluted out by growth. Enzyme activity increased in ammonia-starved, phosphate-limited cultures and in the ammonia 'pulse' system when the added ammonia had been utilised. These increases in enzyme activity were prevented by the presence of 100 mug/ml cycloheximide. GS activity was inversely related to the intracellular concentration of glutamate."}
{"id": "PMID:13761", "title": "Monoamine metabolism in human brain.", "content": "Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.", "contents": "Monoamine metabolism in human brain. Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system."}
{"id": "PMID:13762", "title": "[Management of second stage of labour: observations, reflections, advices (author's transl)].", "content": "All vaginal deliveries of the Department of Obstetrics and Gynecology of the University Basel (N = 4081) during the year 74/73 and of the University T\u00fcbingen (N = 3249) 75/74 were analysed using an IBM-system 370/135 Only alive singletons beyond the 28th week of gestation were analysed. Clinical management was quite different in the two departments; the incidence of vaginal operations (Basal 11.2%, T\u00fcbingen 12.6%), however, as well as the distribution of pH-values and Apgar-scores after 1 min were quite similar. Basel: Acidotic risk (i.e. pHUA less than 7.200) 13.5%, severe acidotic risk (i.e. pHUA less than 7.100) 1.55%, low Apgar-scores (1--3) 0.7%. T\u00fcbingen: :12.3%, 2.11%, 1.6%. 3.5% of all parturients (Basel) had duration of second stage of labour with  active maternal pressure support lasting more than 30 min. In two highly selected samples differing only with regard to the occurrence of cord-entanglements at birth (N1 = 1755, N2 = 1098) the association (rank correlation method according to Kendall) between the parameters of the fetal acid-base balance and the duration of second stage of labour as well as duration of the period with \"active bearing down\" was studied. Without cord encirclements pH in the umbilical artery fall --0.087 and in the umbilical vein --0.115 units and with cord complications the values amounted to --0.062 (UA) and --0.120 (UV) respectively pro 60 min duration of second stage with \"bearing down efforts\". Analogous computations for pCO2, pO2 and HbO2 are presented. Apgar-scores in these samples showed a very loose connection with the time variables. From these data the conclusion is drawn that the indication to perform vaginal operations for termination of delivery should not primarily be governed by the factor time but rather by the whole obstetrical situation i.e. the possible fetal risk of the intervention. This holds only if maternal welfare is established and fetal well being is monitored continuously.", "contents": "[Management of second stage of labour: observations, reflections, advices (author's transl)]. All vaginal deliveries of the Department of Obstetrics and Gynecology of the University Basel (N = 4081) during the year 74/73 and of the University T\u00fcbingen (N = 3249) 75/74 were analysed using an IBM-system 370/135 Only alive singletons beyond the 28th week of gestation were analysed. Clinical management was quite different in the two departments; the incidence of vaginal operations (Basal 11.2%, T\u00fcbingen 12.6%), however, as well as the distribution of pH-values and Apgar-scores after 1 min were quite similar. Basel: Acidotic risk (i.e. pHUA less than 7.200) 13.5%, severe acidotic risk (i.e. pHUA less than 7.100) 1.55%, low Apgar-scores (1--3) 0.7%. T\u00fcbingen: :12.3%, 2.11%, 1.6%. 3.5% of all parturients (Basel) had duration of second stage of labour with  active maternal pressure support lasting more than 30 min. In two highly selected samples differing only with regard to the occurrence of cord-entanglements at birth (N1 = 1755, N2 = 1098) the association (rank correlation method according to Kendall) between the parameters of the fetal acid-base balance and the duration of second stage of labour as well as duration of the period with \"active bearing down\" was studied. Without cord encirclements pH in the umbilical artery fall --0.087 and in the umbilical vein --0.115 units and with cord complications the values amounted to --0.062 (UA) and --0.120 (UV) respectively pro 60 min duration of second stage with \"bearing down efforts\". Analogous computations for pCO2, pO2 and HbO2 are presented. Apgar-scores in these samples showed a very loose connection with the time variables. From these data the conclusion is drawn that the indication to perform vaginal operations for termination of delivery should not primarily be governed by the factor time but rather by the whole obstetrical situation i.e. the possible fetal risk of the intervention. This holds only if maternal welfare is established and fetal well being is monitored continuously."}
{"id": "PMID:13763", "title": "Antibiotics produced by Streptomyces olivaceus 142. I. Characterization of the FPG mutant and conditions of production of antibiotic WR 142-FPG.", "content": "By treating the Streptomyces olivaceus 142 strain simultaneously with ethyleneimine and UV radiation, the FPG mutant was isolated, which was characterized by the fact that in submerged cultures it produces a cytotoxic substance for fibroblasts and tumor cells and inhibits growth of pathogenic fungi. The mutant differs from other strains not only in having a different spectrum of antimicrobial activity, but also by taxonomic properties such as color of the aerial mycelium, liquefaction of gelatin, growth on cellulose, production of ammonia and nitrate reduction. An optimal culture medium and conditions of biosynthesis of the antibiotic in submerged cultures on the shaking machine and in 20-liter fermentation tanks were elaborated. The active substance was designated by the symbol WR 142-FPG.", "contents": "Antibiotics produced by Streptomyces olivaceus 142. I. Characterization of the FPG mutant and conditions of production of antibiotic WR 142-FPG. By treating the Streptomyces olivaceus 142 strain simultaneously with ethyleneimine and UV radiation, the FPG mutant was isolated, which was characterized by the fact that in submerged cultures it produces a cytotoxic substance for fibroblasts and tumor cells and inhibits growth of pathogenic fungi. The mutant differs from other strains not only in having a different spectrum of antimicrobial activity, but also by taxonomic properties such as color of the aerial mycelium, liquefaction of gelatin, growth on cellulose, production of ammonia and nitrate reduction. An optimal culture medium and conditions of biosynthesis of the antibiotic in submerged cultures on the shaking machine and in 20-liter fermentation tanks were elaborated. The active substance was designated by the symbol WR 142-FPG."}
{"id": "PMID:13764", "title": "Search for new aminoguanidine derivatives with immunosuppressive and cytostatic properties. I. Reactions of amino-, nitroamino- and diaminoguanidine with acetylpyruvic acid ethyl ester.", "content": "Reactions of amino-, nitroamino- and diaminoguanidine (I, II, III) with acetylpyruvic acid ethyl ester (IV) at varying pH of the medium were studied. It was found that the nucleophilic hydrazine NH2 group of compounds I, II, and III) attacks the keto group of ester IV in position gamma or alpha. The newly synthesized compounds were submitted to biological evaluation.", "contents": "Search for new aminoguanidine derivatives with immunosuppressive and cytostatic properties. I. Reactions of amino-, nitroamino- and diaminoguanidine with acetylpyruvic acid ethyl ester. Reactions of amino-, nitroamino- and diaminoguanidine (I, II, III) with acetylpyruvic acid ethyl ester (IV) at varying pH of the medium were studied. It was found that the nucleophilic hydrazine NH2 group of compounds I, II, and III) attacks the keto group of ester IV in position gamma or alpha. The newly synthesized compounds were submitted to biological evaluation."}
{"id": "PMID:13765", "title": "Sustrate-specificity of glucomylase (E.C. 3.2.1.3) exemplified by p-nitroaniline n-glucosides.", "content": "The present paper supplements the previous investigations on the mechanism of reactions catalyzed by amylolytic enzymes. The performed experiments corroborated the data on transglucosylative properties of animal glucoamylases which were found to depend on the structure and concentration of substrate. The p-nitroanilines were first introduced in this type of research enabling to find the differences of activity mechanism of animal glucoamylases and Aspergillus niger glucoamylase. In complement to the data reported by Japanese students the transglucosylative properties of glucoamylases were shown to depend not only on the enzyme origin and substrate concentration but also on the chemical composition of applied substrate and concentration of hydrogen ions in the reaction medium.", "contents": "Sustrate-specificity of glucomylase (E.C. 3.2.1.3) exemplified by p-nitroaniline n-glucosides. The present paper supplements the previous investigations on the mechanism of reactions catalyzed by amylolytic enzymes. The performed experiments corroborated the data on transglucosylative properties of animal glucoamylases which were found to depend on the structure and concentration of substrate. The p-nitroanilines were first introduced in this type of research enabling to find the differences of activity mechanism of animal glucoamylases and Aspergillus niger glucoamylase. In complement to the data reported by Japanese students the transglucosylative properties of glucoamylases were shown to depend not only on the enzyme origin and substrate concentration but also on the chemical composition of applied substrate and concentration of hydrogen ions in the reaction medium."}
{"id": "PMID:13766", "title": "Effect of acid pH, salts, and temperature on the infectivity and physical integrity of enteroviruses.", "content": "At 2 degrees and 30 degrees C, enteroviruses are more stable on the acid than on the alkaline side of neutrality. In the range from pH 3 to 9, temperature is so influential that the fastest inactivation rate at 2 degrees C is slower than the slowest inactivation rate at 30 degrees C. Specific ions or salts also affect the rate of inactivation of enteroviruses. NaCl and other chloride salts enhance the inactivation of poliovirus at pH 3. NaCl is considerably less effective against poliovirus in the range of pH 4.5 to 7.0 than at pH less than 4.5. Loss of RNA infectivity of the virus particle proceeds as rapidly as the loss of infectivity of the particle itself, except at pH 3 in the presence of MgCl2. Inactivation results in alterations to the physical integrity of enteroviruses. At pH 5 and 7, RNA hydrolysis of poliovirus particles occurs; and at pH3, 5,6, and 7 the nucleic acid becomes susceptible to ribonuclease. Only virus particles inactivated at pH 3 show a sensitivity to chymotrypsin. The hemagglutinins of echovirus type 7 are destroyed during inactivation at pH 3,4,5, and 6; but at pH 6 this alteration precedes the loss of infectivity. The pH of the suspension is a primary determinant of the mechanism of virus destruction and possibly of the loss of infectivity at these temperatures.", "contents": "Effect of acid pH, salts, and temperature on the infectivity and physical integrity of enteroviruses. At 2 degrees and 30 degrees C, enteroviruses are more stable on the acid than on the alkaline side of neutrality. In the range from pH 3 to 9, temperature is so influential that the fastest inactivation rate at 2 degrees C is slower than the slowest inactivation rate at 30 degrees C. Specific ions or salts also affect the rate of inactivation of enteroviruses. NaCl and other chloride salts enhance the inactivation of poliovirus at pH 3. NaCl is considerably less effective against poliovirus in the range of pH 4.5 to 7.0 than at pH less than 4.5. Loss of RNA infectivity of the virus particle proceeds as rapidly as the loss of infectivity of the particle itself, except at pH 3 in the presence of MgCl2. Inactivation results in alterations to the physical integrity of enteroviruses. At pH 5 and 7, RNA hydrolysis of poliovirus particles occurs; and at pH3, 5,6, and 7 the nucleic acid becomes susceptible to ribonuclease. Only virus particles inactivated at pH 3 show a sensitivity to chymotrypsin. The hemagglutinins of echovirus type 7 are destroyed during inactivation at pH 3,4,5, and 6; but at pH 6 this alteration precedes the loss of infectivity. The pH of the suspension is a primary determinant of the mechanism of virus destruction and possibly of the loss of infectivity at these temperatures."}
{"id": "PMID:13767", "title": "Investigation on the infection of cucumber mesophyll protoplasts with cucumber mosaic virus.", "content": "Isolated protoplasts from the first leaf mesophyll of cucumber plants have been successfully infected in vitro with cucumber mosaic virus (CMV). Virus instability before, during and after inoculation of the protoplasts resulted in low infectivities when extracts were assayed on cowpea; however, viral RNA extraction improved the bioassay technique. Attempts to optimize inoculation and incubation of protoplasts are outlined, incorporating the improved assay.", "contents": "Investigation on the infection of cucumber mesophyll protoplasts with cucumber mosaic virus. Isolated protoplasts from the first leaf mesophyll of cucumber plants have been successfully infected in vitro with cucumber mosaic virus (CMV). Virus instability before, during and after inoculation of the protoplasts resulted in low infectivities when extracts were assayed on cowpea; however, viral RNA extraction improved the bioassay technique. Attempts to optimize inoculation and incubation of protoplasts are outlined, incorporating the improved assay."}
{"id": "PMID:13768", "title": "Thymidine-kinase in cytomegalovirus infected cells.", "content": "In human diploid fibroblast LEP cells infected with AD169 strain of human cytomegalovirus (CMV) a sharp increase of cytosol thymidine kinase activity was observed. The properties of the cytosol enzymes from infected and non-infected cells were compared. No significant differences between the enzymes from infected and control cells were observed in substrate specificity, pH dependence, thermostability and relative electrophoretic mobility. Human sera containing high titres of CMV complement-fixing antibodies did not neutralize the enzyme from infected cells. It is concluded from these results that the increase of cytosol thymidinekinase activity in CMV-infected cells was due to an enhancement of cellular thymidine kinase.", "contents": "Thymidine-kinase in cytomegalovirus infected cells. In human diploid fibroblast LEP cells infected with AD169 strain of human cytomegalovirus (CMV) a sharp increase of cytosol thymidine kinase activity was observed. The properties of the cytosol enzymes from infected and non-infected cells were compared. No significant differences between the enzymes from infected and control cells were observed in substrate specificity, pH dependence, thermostability and relative electrophoretic mobility. Human sera containing high titres of CMV complement-fixing antibodies did not neutralize the enzyme from infected cells. It is concluded from these results that the increase of cytosol thymidinekinase activity in CMV-infected cells was due to an enhancement of cellular thymidine kinase."}
{"id": "PMID:13769", "title": "[Role of viral-bacterial associations in meningitis in children].", "content": "A total of 50 section cases of meningitis in children were investigated. All patients revealed acute viral respiratory infections with generalization, including lesions of the central nervous system (CNS). In 14 children moreover meningococcal infection was diagnosed. In 30 children lesions of the CNS were due to mixed bacterial microflora. In 6 children along with acute viral respiratory infections (AVRI) mycoplasmosis was also revealed. Etiology of the process was determined on the basis of characteristic structural changes in the CNS and other organs, findings of virological and bacteriological investigations. In the majority of children the intravascular blood coagulation was observed. Waterhouse-Friderichsen's syndrome was revealed mainly in meningococcal infection. In order to ascertain the data obtained case records of 120 children, who had undergone treatment in connection with meningococcal infection, were analysed. It turned out that all 42 children, who had developed this disease independently, recovered. Combination of the disease with AVRI led to fatal outcomes in 12 cases out of 72.", "contents": "[Role of viral-bacterial associations in meningitis in children]. A total of 50 section cases of meningitis in children were investigated. All patients revealed acute viral respiratory infections with generalization, including lesions of the central nervous system (CNS). In 14 children moreover meningococcal infection was diagnosed. In 30 children lesions of the CNS were due to mixed bacterial microflora. In 6 children along with acute viral respiratory infections (AVRI) mycoplasmosis was also revealed. Etiology of the process was determined on the basis of characteristic structural changes in the CNS and other organs, findings of virological and bacteriological investigations. In the majority of children the intravascular blood coagulation was observed. Waterhouse-Friderichsen's syndrome was revealed mainly in meningococcal infection. In order to ascertain the data obtained case records of 120 children, who had undergone treatment in connection with meningococcal infection, were analysed. It turned out that all 42 children, who had developed this disease independently, recovered. Combination of the disease with AVRI led to fatal outcomes in 12 cases out of 72."}
{"id": "PMID:13770", "title": "[Structural and functional characteristics of the spleen in systemic and local allogenic graft versus host reaction].", "content": "Morphological and histochemical characteristics of the spleen in the systemic and locally induced in the spleen transplant host reaction were compared. In both forms there were observed infiltration of the organ with macrophages and pyroninophilial blasts characterized by a high level of the activity of enzymes of lysosomas and a hexosemonophosphate cycle. In the process of interaction between genetically heterogenous mononuclear cells the disturbance of enzymatic processes in them and in the adjacent cellular elements took place, and susequently they underwent necrosis. Most frequently this process was observed in lymphoid follicles. The destructive component in the spleen tissue was more pronounced in the systemic transplant against host reaction.", "contents": "[Structural and functional characteristics of the spleen in systemic and local allogenic graft versus host reaction]. Morphological and histochemical characteristics of the spleen in the systemic and locally induced in the spleen transplant host reaction were compared. In both forms there were observed infiltration of the organ with macrophages and pyroninophilial blasts characterized by a high level of the activity of enzymes of lysosomas and a hexosemonophosphate cycle. In the process of interaction between genetically heterogenous mononuclear cells the disturbance of enzymatic processes in them and in the adjacent cellular elements took place, and susequently they underwent necrosis. Most frequently this process was observed in lymphoid follicles. The destructive component in the spleen tissue was more pronounced in the systemic transplant against host reaction."}
{"id": "PMID:13773", "title": "Murray Valley encephalitis virus infection in mosquitoes and domestic fowls in Queensland, 1974.", "content": "Field studies during an epidemic of Murray Valley encephalitis (MVE) led to the isolation of MVE virus from a pool of mosquitoes (Culex annulirostris) and a sentinel chicken from Charleville, south-west Queensland. A high proportion of domestic fowls at Charleville had antibody to MVE virus at the beginning of February 1974, in advance of the first case recognized in Queensland and allowing early warning from health authorities. A survey of antibody in domestic fowls in mid-1974 suggested widespread activity of MVE virus in western and east-central Queensland. Virus isolation and serological studies showed activity in south-west Queensland of three other viruses known to infect man, Ross River, Sindbis and Kunjin viruses.", "contents": "Murray Valley encephalitis virus infection in mosquitoes and domestic fowls in Queensland, 1974. Field studies during an epidemic of Murray Valley encephalitis (MVE) led to the isolation of MVE virus from a pool of mosquitoes (Culex annulirostris) and a sentinel chicken from Charleville, south-west Queensland. A high proportion of domestic fowls at Charleville had antibody to MVE virus at the beginning of February 1974, in advance of the first case recognized in Queensland and allowing early warning from health authorities. A survey of antibody in domestic fowls in mid-1974 suggested widespread activity of MVE virus in western and east-central Queensland. Virus isolation and serological studies showed activity in south-west Queensland of three other viruses known to infect man, Ross River, Sindbis and Kunjin viruses."}
{"id": "PMID:13774", "title": "Clinical evaluation of a dialysate regeneration system for maintenance haemodialysis.", "content": "A commercially available sorbent-based dialysate regeneration system has been compared to conventional single-pass dialysate delivery systems for treatment periods of six weeks in 13 patients on maintenance dialysis. The results of treatment were virtually identical in comparing sorbent and conventional systems except that seven of the eight patients using 2-5 M2 dialysers for 3--4 hours thrice per week developed asymptomatic metabolic acidosis with the dialysate regeneration system. This complication was not seen in the five patients using 1-3 M2 dialysers and having a 6--7 hour treatment thrice weekly. Dialysate regeneration systems are particularly suited for use when water supplies are limited or of insufficient purity for single-pass dialysis, and when a portable artificial kidney is required. To avoid metabolic acidosis with this system, using currently available disposable cartridges, each dialysis treatment should be of at least 4-5 hours duration.", "contents": "Clinical evaluation of a dialysate regeneration system for maintenance haemodialysis. A commercially available sorbent-based dialysate regeneration system has been compared to conventional single-pass dialysate delivery systems for treatment periods of six weeks in 13 patients on maintenance dialysis. The results of treatment were virtually identical in comparing sorbent and conventional systems except that seven of the eight patients using 2-5 M2 dialysers for 3--4 hours thrice per week developed asymptomatic metabolic acidosis with the dialysate regeneration system. This complication was not seen in the five patients using 1-3 M2 dialysers and having a 6--7 hour treatment thrice weekly. Dialysate regeneration systems are particularly suited for use when water supplies are limited or of insufficient purity for single-pass dialysis, and when a portable artificial kidney is required. To avoid metabolic acidosis with this system, using currently available disposable cartridges, each dialysis treatment should be of at least 4-5 hours duration."}
{"id": "PMID:13775", "title": "Effects of induced cryptorchidism in bulls.", "content": "Ninety bull calves were made cryptorchid by forcing the testes into the abdominal cavity and ablating the scrotum with elastrator rings. Normal spermatogenesis was seen following histological examination of some of the testes approximately 17 months after the operation. No effect on bull behaviour was noted in the cryptorchids although plasma testosterone levels were lower than those reported for bulls. It is possible that this method may leave some of the cryptorchids fertile.", "contents": "Effects of induced cryptorchidism in bulls. Ninety bull calves were made cryptorchid by forcing the testes into the abdominal cavity and ablating the scrotum with elastrator rings. Normal spermatogenesis was seen following histological examination of some of the testes approximately 17 months after the operation. No effect on bull behaviour was noted in the cryptorchids although plasma testosterone levels were lower than those reported for bulls. It is possible that this method may leave some of the cryptorchids fertile."}
{"id": "PMID:13781", "title": "[Tubular structure and germ cell distribution of cryptorchid or normal testes in early childhood (author's transl)].", "content": "Many recent publications have demonstrated that the cryptorchid testicle (and, to a lesser extent, the descended partner) are progressively injured from the second year of life onwards. Do these injuries occur in an organ which has been healthy up to this time or are they superimposed on a structurally abnormal testicle? In order to answer this, parts of cryptorchid testicles, of the descended partners, and of normal testicles were compared by histological examination of serial sections. Parts of four testes from children aged 4-7 months (2 specimens obtained by biopsy and 2 from autoptic material) and parts of four testes from children 1 1/2 years old (2 obtained by biopsy and 2 from autoptic material) were examined. The biopsies were fixed in Stieve's fixative. Tissue samples from clinically healthy children who had died suddenly were fixed in 4% formalin. The tissue was embedded in paraffin and sectioned serially; 6 mum sections were stained with HE. The spermatogonia in each cross-section and in each oblique section of a same tubule were counted and the counts of the latter were adjusted to a cross-section 50-60 mum in diameter. This counting technique did not alter the density of spermatogonia. The graphs present data on the density of spermatogonia through the lengths of the tubules examined and demonstrate tubular branching and blind ends. In the first year of life the cryptorchid testis and its descended partner showed repeated long sections lacking spermatogonia in the same tubule, whereas in normal testes the spermatogonia were more evenly distributed. The cryptorchid testis showed increased tubule branching in the areas examined. In the second year of life the tubules of the cryptorchid testis and its descended partner manifest areas free of germ cells, increased branching, and blind ends. The cryptorchid testis also had a tubule completely free of spermatogonia. The germ cell-free parts were always associated with a smaller tubule diameter than normal. The normal testes did not disclose increased branching or spermatogonium-free areas within similar lengths of tubules and showed an even distribution of spermatogonia. The different distribution of spermatogonia within the tubules and the increased branching of the tubules in cryptorchid testes indicate a previous disturbance of testis development.", "contents": "[Tubular structure and germ cell distribution of cryptorchid or normal testes in early childhood (author's transl)]. Many recent publications have demonstrated that the cryptorchid testicle (and, to a lesser extent, the descended partner) are progressively injured from the second year of life onwards. Do these injuries occur in an organ which has been healthy up to this time or are they superimposed on a structurally abnormal testicle? In order to answer this, parts of cryptorchid testicles, of the descended partners, and of normal testicles were compared by histological examination of serial sections. Parts of four testes from children aged 4-7 months (2 specimens obtained by biopsy and 2 from autoptic material) and parts of four testes from children 1 1/2 years old (2 obtained by biopsy and 2 from autoptic material) were examined. The biopsies were fixed in Stieve's fixative. Tissue samples from clinically healthy children who had died suddenly were fixed in 4% formalin. The tissue was embedded in paraffin and sectioned serially; 6 mum sections were stained with HE. The spermatogonia in each cross-section and in each oblique section of a same tubule were counted and the counts of the latter were adjusted to a cross-section 50-60 mum in diameter. This counting technique did not alter the density of spermatogonia. The graphs present data on the density of spermatogonia through the lengths of the tubules examined and demonstrate tubular branching and blind ends. In the first year of life the cryptorchid testis and its descended partner showed repeated long sections lacking spermatogonia in the same tubule, whereas in normal testes the spermatogonia were more evenly distributed. The cryptorchid testis showed increased tubule branching in the areas examined. In the second year of life the tubules of the cryptorchid testis and its descended partner manifest areas free of germ cells, increased branching, and blind ends. The cryptorchid testis also had a tubule completely free of spermatogonia. The germ cell-free parts were always associated with a smaller tubule diameter than normal. The normal testes did not disclose increased branching or spermatogonium-free areas within similar lengths of tubules and showed an even distribution of spermatogonia. The different distribution of spermatogonia within the tubules and the increased branching of the tubules in cryptorchid testes indicate a previous disturbance of testis development."}
{"id": "PMID:13782", "title": "Genetics of peroxisomal enzymes in the mouse: nonlinkage of D-amino acid oxidase locus (Dao) to catalase (Cs) and L-alpha-hydroxyacid oxidase (Hao-1) loci on chromosome 2.", "content": "An electrophoretic polymorphism of the peroxisomal enzyme D-amino acid oxidase was observed in NZC strain Mus musculus. F1 (NZC X BALB/c) mice showed a codominant allcle two-banded phenotype which is inconsistent with the dimeric subunit structure reported for this enzyme in other species. The enzyme locus (Dao) was shown to segregate independently of Hao-1, encoding the peroxisomal enzyme hydroxyacid oxidase (liver on A4 isozyme). Thus Dao is not linked to previously mapped peroxisomal enzyme loci, Hao-1 and Cs, closely localized on chromosome 2.", "contents": "Genetics of peroxisomal enzymes in the mouse: nonlinkage of D-amino acid oxidase locus (Dao) to catalase (Cs) and L-alpha-hydroxyacid oxidase (Hao-1) loci on chromosome 2. An electrophoretic polymorphism of the peroxisomal enzyme D-amino acid oxidase was observed in NZC strain Mus musculus. F1 (NZC X BALB/c) mice showed a codominant allcle two-banded phenotype which is inconsistent with the dimeric subunit structure reported for this enzyme in other species. The enzyme locus (Dao) was shown to segregate independently of Hao-1, encoding the peroxisomal enzyme hydroxyacid oxidase (liver on A4 isozyme). Thus Dao is not linked to previously mapped peroxisomal enzyme loci, Hao-1 and Cs, closely localized on chromosome 2."}
{"id": "PMID:13780", "title": "Myocardial function during acute hypoxia in the calf.", "content": "Hemodynamics and myocardial contractility were evaluated in five unanesthetized calves during acute hypocapnic and isocapnic hypoxia and during acute hypocapnic hypoxia with beta-adrenergic blockade. Both hypocapnic and isocapnic hypoxia, with mean PaO2 levels of 33.1 and 39.1 mm Hg respectively, produced a decline in stroke volume and index, while cardiac output and index were maintained at normoxic control levels by an increase in heart rate. Evaluation of myocardial contractility indices suggested an augmentation of left ventricular contractility during both hypocapnic and isocapnic hypoxia. Beta-adrenergic blockade effectively eliminated the increase in left ventricular contractility during hypocapnic hypoxia, suggesting an important role of the adrenergic nervous system in the genesis of the cardiovascular response of the calf to acute hypoxia. Right ventricular contractility indices failed to demonstrate a clear-cut augmentation of contractility during hypocapnic and isocapnic hypoxia when the concurrent increase in afterload was considered. Mean pulmonary arterial blood pressure rose significantly during hypocapnic and isocapnic hypoxia. The pulmonary pressor response to hypocapnic hypoxia was significantly augmented by beta blockade, indicating that the autonomic nervous system is capable of modifying the hypoxic pulmonary pressor response in this species.", "contents": "Myocardial function during acute hypoxia in the calf. Hemodynamics and myocardial contractility were evaluated in five unanesthetized calves during acute hypocapnic and isocapnic hypoxia and during acute hypocapnic hypoxia with beta-adrenergic blockade. Both hypocapnic and isocapnic hypoxia, with mean PaO2 levels of 33.1 and 39.1 mm Hg respectively, produced a decline in stroke volume and index, while cardiac output and index were maintained at normoxic control levels by an increase in heart rate. Evaluation of myocardial contractility indices suggested an augmentation of left ventricular contractility during both hypocapnic and isocapnic hypoxia. Beta-adrenergic blockade effectively eliminated the increase in left ventricular contractility during hypocapnic hypoxia, suggesting an important role of the adrenergic nervous system in the genesis of the cardiovascular response of the calf to acute hypoxia. Right ventricular contractility indices failed to demonstrate a clear-cut augmentation of contractility during hypocapnic and isocapnic hypoxia when the concurrent increase in afterload was considered. Mean pulmonary arterial blood pressure rose significantly during hypocapnic and isocapnic hypoxia. The pulmonary pressor response to hypocapnic hypoxia was significantly augmented by beta blockade, indicating that the autonomic nervous system is capable of modifying the hypoxic pulmonary pressor response in this species."}
{"id": "PMID:13783", "title": "The maximum activities of hexokinase, phosphorylase, phosphofructokinase, glycerol phosphate dehydrogenases, lactate dehydrogenase, octopine dehydrogenase, phosphoenolpyruvate carboxykinase, nucleoside diphosphatekinase, glutamate-oxaloacetate transaminase and arginine kinase in relation to carbohydrate utilization in muscles from marine invertebrates.", "content": "Comparison of the activities of hexokinase, phosphorylase and phosphofructokinase in muscles from marine invertebrates indicates that they can be divided into three groups. First, the activities of the three enzymes are low in coelenterate muscles, catch muscles of molluscs and muscles of echinoderms; this indicates a low rate of carbohydrate (and energy) utilization by these muscles. Secondly, high activities of phosphorylase and phosphofructokinase relative to those of hexokinase are found in, for example, lobster abdominal and scallop snap muscles; this indicates that these muscles depend largely on anaerobic degradation of glycogen for energy production. Thirdly, high activities of hexokinase are found in the radular muscles of prosobranch molluscs and the fin muscles of squids; this indicates a high capacity for glucose utilization, which is consistent with the high activities of enzymes of the tricarboxylic acid cycle in these muscles [Alp, Newsholme & Zammit (1976) Biochem. J. 154, 689-700]. 2. The activities of lactate dehydrogenase, octopine dehydrogenase, phosphoenolpyruvate carboxykinase, cytosolic and mitochondrial glycerol 3-phosphate dehydrogenase and glutamate-oxaloacetate transaminase were measured in order to provide a qualitative indication of the importance of different processes for oxidation of glycolytically formed NADH. The muscles are divided into four groups: those that have a high activity of lactate dehydrogenase relative to the activities of phosphofructokinase (e.g. crustacean muscles); those that have high activities of octopine dehydrogenase but low activities of lactate dehydrogenase (e.g. scallop snap muscle); those that have moderate activities of both lactate dehydrogenase and octopine dehydrogenase (radular muscles of prosobranchs), and those that have low activities of both lactate dehydrogenase and octopine dehydrogenase, but which possess activities of phosphoenolpyruvate carboxykinase (oyster adductor muscles). It is suggested that, under anaerobic conditions, muscles of marine invertebrates form lactate and/or octopine or succinate (or similar end product) according to the activities of the enzymes present in the muscles (see above). The muscles investigated possess low activities of cytosolic glycerol 3-phosphate dehydrogenase, which indicates that glycerol phosphate formation is quantitatively unimportant under anaerobic conditions, and low activities of mitochondrial glycerol phosphate dehydrogenase, which indicates that the glycerol phosphate cycle is unimportant in the re-oxidation of glycolytically produced NADH in these muscles under aerobic conditions. Conversely, high activities of glutamate-oxaloacetate transaminase are present in some muscles, which indicates that the malate-aspartate cycle may be important in oxidation of glycolytically produced NADH under aerobic conditions. 3. High activities of nucleoside diphosphate kinase were found in muscles that function for prolonged periods under anaerobic conditions (e.g...", "contents": "The maximum activities of hexokinase, phosphorylase, phosphofructokinase, glycerol phosphate dehydrogenases, lactate dehydrogenase, octopine dehydrogenase, phosphoenolpyruvate carboxykinase, nucleoside diphosphatekinase, glutamate-oxaloacetate transaminase and arginine kinase in relation to carbohydrate utilization in muscles from marine invertebrates. Comparison of the activities of hexokinase, phosphorylase and phosphofructokinase in muscles from marine invertebrates indicates that they can be divided into three groups. First, the activities of the three enzymes are low in coelenterate muscles, catch muscles of molluscs and muscles of echinoderms; this indicates a low rate of carbohydrate (and energy) utilization by these muscles. Secondly, high activities of phosphorylase and phosphofructokinase relative to those of hexokinase are found in, for example, lobster abdominal and scallop snap muscles; this indicates that these muscles depend largely on anaerobic degradation of glycogen for energy production. Thirdly, high activities of hexokinase are found in the radular muscles of prosobranch molluscs and the fin muscles of squids; this indicates a high capacity for glucose utilization, which is consistent with the high activities of enzymes of the tricarboxylic acid cycle in these muscles [Alp, Newsholme & Zammit (1976) Biochem. J. 154, 689-700]. 2. The activities of lactate dehydrogenase, octopine dehydrogenase, phosphoenolpyruvate carboxykinase, cytosolic and mitochondrial glycerol 3-phosphate dehydrogenase and glutamate-oxaloacetate transaminase were measured in order to provide a qualitative indication of the importance of different processes for oxidation of glycolytically formed NADH. The muscles are divided into four groups: those that have a high activity of lactate dehydrogenase relative to the activities of phosphofructokinase (e.g. crustacean muscles); those that have high activities of octopine dehydrogenase but low activities of lactate dehydrogenase (e.g. scallop snap muscle); those that have moderate activities of both lactate dehydrogenase and octopine dehydrogenase (radular muscles of prosobranchs), and those that have low activities of both lactate dehydrogenase and octopine dehydrogenase, but which possess activities of phosphoenolpyruvate carboxykinase (oyster adductor muscles). It is suggested that, under anaerobic conditions, muscles of marine invertebrates form lactate and/or octopine or succinate (or similar end product) according to the activities of the enzymes present in the muscles (see above). The muscles investigated possess low activities of cytosolic glycerol 3-phosphate dehydrogenase, which indicates that glycerol phosphate formation is quantitatively unimportant under anaerobic conditions, and low activities of mitochondrial glycerol phosphate dehydrogenase, which indicates that the glycerol phosphate cycle is unimportant in the re-oxidation of glycolytically produced NADH in these muscles under aerobic conditions. Conversely, high activities of glutamate-oxaloacetate transaminase are present in some muscles, which indicates that the malate-aspartate cycle may be important in oxidation of glycolytically produced NADH under aerobic conditions. 3. High activities of nucleoside diphosphate kinase were found in muscles that function for prolonged periods under anaerobic conditions (e.g..."}
{"id": "PMID:13784", "title": "Phosphate transport into brush-border membrane vesicles isolated from rat small intestine.", "content": "Uptake of Pi into brush-border membrane vesicles isolated from rat small intestine was investigated by a rapid filtration technique. The following results were obtained. 1. At pH 7.4 in the presence of a NaCl gradient across the membrane (sodium concentration in the medium higher than sodium concentration in the vesicles), phosphate was taken up by a saturable transport system, which was competitively inhibited by arsenate. Phosphate entered the same osmotically reactive space as D-glucose, which indicates that transport into the vesicles rather than binding to the membranes was determined. 2. The amount of phosphate taken up initially was increased about fourfold by lowering the pH from 7.4 to 6.0.3. When Na+ was replaced by K+, Rb+ or Cs+, the initial rate of uptake decreased at pH 7.4 but was not altered at pH 6.0.4. Experiments with different anions (SCN-,Cl-, SO42-) and with ionophores (valinomycin, monactin) showed that at pH 7.4 phosphate transport in the presence of a Na+ gradient is almost independent of the electrical potential across the vesicle membrane, whereas at pH 6.0 phosphate transport involves the transfer of negative charge. It is concluded that intestinal brush-border membranes contain a Na+/phosphate co-transport system, which catalyses under physiological conditions an electroneutral entry of Pi and Na+ into the intestinal epithelial cell. In contrast with the kidney, probably univalent phosphate and one Na+ ion instead of bivalent phosphate and two Na+ ions are transported together.", "contents": "Phosphate transport into brush-border membrane vesicles isolated from rat small intestine. Uptake of Pi into brush-border membrane vesicles isolated from rat small intestine was investigated by a rapid filtration technique. The following results were obtained. 1. At pH 7.4 in the presence of a NaCl gradient across the membrane (sodium concentration in the medium higher than sodium concentration in the vesicles), phosphate was taken up by a saturable transport system, which was competitively inhibited by arsenate. Phosphate entered the same osmotically reactive space as D-glucose, which indicates that transport into the vesicles rather than binding to the membranes was determined. 2. The amount of phosphate taken up initially was increased about fourfold by lowering the pH from 7.4 to 6.0.3. When Na+ was replaced by K+, Rb+ or Cs+, the initial rate of uptake decreased at pH 7.4 but was not altered at pH 6.0.4. Experiments with different anions (SCN-,Cl-, SO42-) and with ionophores (valinomycin, monactin) showed that at pH 7.4 phosphate transport in the presence of a Na+ gradient is almost independent of the electrical potential across the vesicle membrane, whereas at pH 6.0 phosphate transport involves the transfer of negative charge. It is concluded that intestinal brush-border membranes contain a Na+/phosphate co-transport system, which catalyses under physiological conditions an electroneutral entry of Pi and Na+ into the intestinal epithelial cell. In contrast with the kidney, probably univalent phosphate and one Na+ ion instead of bivalent phosphate and two Na+ ions are transported together."}
{"id": "PMID:13785", "title": "Validation of a simple radiochemical assay measuring hydrolysis of choline-labelled microsomal phosphatidylcholine by phospholipase C. pH-dependence.", "content": "Selective hydrolysis of phosphatidylcholine species, which are selectively radioactively labelled in vivo, does not appear to interfere with a radiochemical assay for hydrolysis of microsomal phosphatidylcholine by C-type phospholipases from Bacillus cereus or Clostridium perfringens. Both phospholipases substantially hydrolysed phosphatidylcholine over the pH range 4.0-10.0.", "contents": "Validation of a simple radiochemical assay measuring hydrolysis of choline-labelled microsomal phosphatidylcholine by phospholipase C. pH-dependence. Selective hydrolysis of phosphatidylcholine species, which are selectively radioactively labelled in vivo, does not appear to interfere with a radiochemical assay for hydrolysis of microsomal phosphatidylcholine by C-type phospholipases from Bacillus cereus or Clostridium perfringens. Both phospholipases substantially hydrolysed phosphatidylcholine over the pH range 4.0-10.0."}
{"id": "PMID:13786", "title": "Transannular dioxygenation of 9,10-dimethyl-1,2-benzanthracene by cytochrome P-450 oxygenase of rat liver.", "content": "9,10-Dimethyl-1,2-benzanthracene is oxygenated by rat liver microsomal cytochrome P-450 oxygenase to its 9,10-epidioxide. This transannular 1,4-peroxide is converted further into the diol by the microsomal preparation and NADPH. These two products constitute the majority of the metabolites found under the conditions described.", "contents": "Transannular dioxygenation of 9,10-dimethyl-1,2-benzanthracene by cytochrome P-450 oxygenase of rat liver. 9,10-Dimethyl-1,2-benzanthracene is oxygenated by rat liver microsomal cytochrome P-450 oxygenase to its 9,10-epidioxide. This transannular 1,4-peroxide is converted further into the diol by the microsomal preparation and NADPH. These two products constitute the majority of the metabolites found under the conditions described."}
{"id": "PMID:13803", "title": "Fatty acid synthesis in aorta. Isolation of fatty acid synthetase from chicken aorta.", "content": "Fatty acid synthesis by subcellular fractions of human aorta was studied by measuring the incorporation of either radioactive acetyl-CoA or malonyl-CoA into long chain fatty acids. The high speed supernatant fraction contained fatty acid synthetase and was capable of de novo fatty acid synthesis. The fatty acid synthetase from chicken aorta was purified 800-fold from the high speed supernatant and was judged to be 10% pure at this level. Its molecular weight was estimated to be 450,000 on the basis of agarose gel filtration chromatography, while under dissociating conditions a molecular weight of 220,000 was obtained on sodium dodecyl sulphate disc gel electrophoresis. Fatty acid synthesis was dependent on acetyl-CoA, malonyl-CoA and NADPH. The major product was free palmitic acid. In enzymatic and physical characteristics the chicken aorta fatty acid synthetase strongly resembles the synthetase isolated from chicken liver. The two enzymes cross-react immuno-chemically and this homology provides the possibility of studying the synthesis and degradation of the aorta synthetase during the development of atherosclerosis.", "contents": "Fatty acid synthesis in aorta. Isolation of fatty acid synthetase from chicken aorta. Fatty acid synthesis by subcellular fractions of human aorta was studied by measuring the incorporation of either radioactive acetyl-CoA or malonyl-CoA into long chain fatty acids. The high speed supernatant fraction contained fatty acid synthetase and was capable of de novo fatty acid synthesis. The fatty acid synthetase from chicken aorta was purified 800-fold from the high speed supernatant and was judged to be 10% pure at this level. Its molecular weight was estimated to be 450,000 on the basis of agarose gel filtration chromatography, while under dissociating conditions a molecular weight of 220,000 was obtained on sodium dodecyl sulphate disc gel electrophoresis. Fatty acid synthesis was dependent on acetyl-CoA, malonyl-CoA and NADPH. The major product was free palmitic acid. In enzymatic and physical characteristics the chicken aorta fatty acid synthetase strongly resembles the synthetase isolated from chicken liver. The two enzymes cross-react immuno-chemically and this homology provides the possibility of studying the synthesis and degradation of the aorta synthetase during the development of atherosclerosis."}
{"id": "PMID:13801", "title": "Effect of altered lymphocyte function on immunologic disorders in NZB/NZW mice.", "content": "NZB/NZW F1 female mice were treated with the immunosuppresive enzyme L-asparaginar antibodies, diminished deposition of gamma-globulins in kidneys, significantly delayed the onset of proteinuria, and reduced deaths from nephritis. These effects were associated with reduction of cellular IgM antibody synthesis to both T-dependent and T-independent antigens, but the graft-versus-host reaction was not affected. After several weeks of therapy, antibodies against Asnase appeared in the circulation, the effect on antibody synthesis was lost, ANA and anti-DNA appeared, followed by proteinuria and deaths from nephritis. Therefore Asnase proved to be an effective therapy in NZB/NZW mice, but its usefulness was limited by the appearance of inactivating antibodies.", "contents": "Effect of altered lymphocyte function on immunologic disorders in NZB/NZW mice. NZB/NZW F1 female mice were treated with the immunosuppresive enzyme L-asparaginar antibodies, diminished deposition of gamma-globulins in kidneys, significantly delayed the onset of proteinuria, and reduced deaths from nephritis. These effects were associated with reduction of cellular IgM antibody synthesis to both T-dependent and T-independent antigens, but the graft-versus-host reaction was not affected. After several weeks of therapy, antibodies against Asnase appeared in the circulation, the effect on antibody synthesis was lost, ANA and anti-DNA appeared, followed by proteinuria and deaths from nephritis. Therefore Asnase proved to be an effective therapy in NZB/NZW mice, but its usefulness was limited by the appearance of inactivating antibodies."}
{"id": "PMID:13805", "title": "Acute-phase reactant protein profiles: an aid to monitoring large bowel cancer by CEA and serum enzymes.", "content": "The profiles of 4 acute-phase reactant proteins (APRPs) (haptoglobin (HPT), alpha1 antitrypsin (AAT), alpha1 acid glycoprotein (AGP) and prealbumin (PALB)) have been studied during the evolution of bowel cancer. Serial measurements of these APRPs can add to the information obtained from measurements of the level of CEA and hepatic enzymes during the monitoring of postoperative patients. There is considerable stability in the profile in a given individual in health, Rises of AAT and AGP are associated with metastases. High levels of HPT may suggest involvement of the bowel wall by recurrent cancer. PALB levels tend to reflect the nutritional status. A discriminant function based on the log CEA, AAT and AGP preoperative blood levels can considerably improve on the predictive value attained using CEA levels alone.", "contents": "Acute-phase reactant protein profiles: an aid to monitoring large bowel cancer by CEA and serum enzymes. The profiles of 4 acute-phase reactant proteins (APRPs) (haptoglobin (HPT), alpha1 antitrypsin (AAT), alpha1 acid glycoprotein (AGP) and prealbumin (PALB)) have been studied during the evolution of bowel cancer. Serial measurements of these APRPs can add to the information obtained from measurements of the level of CEA and hepatic enzymes during the monitoring of postoperative patients. There is considerable stability in the profile in a given individual in health, Rises of AAT and AGP are associated with metastases. High levels of HPT may suggest involvement of the bowel wall by recurrent cancer. PALB levels tend to reflect the nutritional status. A discriminant function based on the log CEA, AAT and AGP preoperative blood levels can considerably improve on the predictive value attained using CEA levels alone."}
{"id": "PMID:13806", "title": "Amino acid sequence of the Anthopleura xanthogrammica heart stimulant, anthopleurin A.", "content": "A highly potent heart stimulant, anthopleurin A, from Anthopleura xanthogrammica was shown to exist as a single polypeptide chain consisting of 49 amino acid residues. The sequence of the peptide was shown to be: Gly-Val-Ser-Cys-Leu-Cys-Asp-Ser-Asp-Gly-Pro-Ser-Val-Arg-Gly-Asn-Thr-Leu-Ser-Gly-Thr-Leu-Trp-Leu-Tyr-Pro-Ser-Gly-Cys-Pro-Ser-Gly-Trp-His-Asn-Cys-Lys-Ala-His-Gly-Pro-Thr-Ile-Gly-Trp-Cys-Cys-Lys-Gln as judged by Edman degradation of the carboxymethylcysteine derivative and the tryptic peptides obtained from the derivative. Although six carboxymethylcysteine residues were present in the polypeptide, no cysteine residues were detectable in the native protein, indicating that there are three cystine residues in anthopleurin A.", "contents": "Amino acid sequence of the Anthopleura xanthogrammica heart stimulant, anthopleurin A. A highly potent heart stimulant, anthopleurin A, from Anthopleura xanthogrammica was shown to exist as a single polypeptide chain consisting of 49 amino acid residues. The sequence of the peptide was shown to be: Gly-Val-Ser-Cys-Leu-Cys-Asp-Ser-Asp-Gly-Pro-Ser-Val-Arg-Gly-Asn-Thr-Leu-Ser-Gly-Thr-Leu-Trp-Leu-Tyr-Pro-Ser-Gly-Cys-Pro-Ser-Gly-Trp-His-Asn-Cys-Lys-Ala-His-Gly-Pro-Thr-Ile-Gly-Trp-Cys-Cys-Lys-Gln as judged by Edman degradation of the carboxymethylcysteine derivative and the tryptic peptides obtained from the derivative. Although six carboxymethylcysteine residues were present in the polypeptide, no cysteine residues were detectable in the native protein, indicating that there are three cystine residues in anthopleurin A."}
{"id": "PMID:13807", "title": "Magnetic resonance studies of the binding of 13C-labeled carbon monoxide to myoglobins and hemoglobins containing modified hemes.", "content": "The effects of changes in the groups attached to the periphery of the porphyrin ring of the heme of various hemoglobin and myoglobins on the environment experienced by the ligand, carbon monoxide, have been studied by observation of the chemical shift of the bound 13CO. The results indicate that the major interaction between bound ligands and substituents around the porphyrin is that transmitted electronically from substituent to ligand. The nature of the protein environment around the ligand and the interaction between the proximal histidine (F8) and the ligand (through the iron atom) impose differences between subunits of hemoglobin and between myoglobins and hemoglobins which are largely, but not entirely, independent of these substituent effects. To assess the influence of protein structure on the chemical shifts of bound ligand, the shifts of 13CO bound to myoglobin and hemoglobins from a wide range of species have also been measured.", "contents": "Magnetic resonance studies of the binding of 13C-labeled carbon monoxide to myoglobins and hemoglobins containing modified hemes. The effects of changes in the groups attached to the periphery of the porphyrin ring of the heme of various hemoglobin and myoglobins on the environment experienced by the ligand, carbon monoxide, have been studied by observation of the chemical shift of the bound 13CO. The results indicate that the major interaction between bound ligands and substituents around the porphyrin is that transmitted electronically from substituent to ligand. The nature of the protein environment around the ligand and the interaction between the proximal histidine (F8) and the ligand (through the iron atom) impose differences between subunits of hemoglobin and between myoglobins and hemoglobins which are largely, but not entirely, independent of these substituent effects. To assess the influence of protein structure on the chemical shifts of bound ligand, the shifts of 13CO bound to myoglobin and hemoglobins from a wide range of species have also been measured."}
{"id": "PMID:13808", "title": "Correlation between the exposure of aromatic chromophores at the surface of the Fc domains of immunoglobulin G and their ability to bind complement.", "content": "The recognition that certain biological effector functions associated with the Fc region of human IgG are mediated exclusively by either the Cgamma2 or Cgamma3 domains prompted a study of some of the physical properties of the isolated domains in an attempt to correlate these with functional differentiation. The degree of aromatic chromophore exposure of intact Fc and fragments corresponding to the Cgamma2 and Cgamma3 domains were determined by solvent perturbation difference spectroscopy using 20% ethylene glycol. For the monomeric Cgamma2 fragment one of the two tryptophans and all four of the tyrosines were exposed to solvent. In the pFc' fragment, which represented a dimer of two intact Cgamma3 domains, an average of 0.4 of the two tryptophans of 3.3 of the five tyrosines per chain were exposed. These data were consistent with the suggested involvement of tryptophan in complement fixation since Cgamma2 binds C1q but pFc' does not. Several fragments derived from the Cgamma3 region had previously been shown to have differing environments for their aromatic side chains from circular dichroism studies. These fragments have now been shown to exhibit different degrees of chromophore exposure to solvent. Removal of the carboxy-termimal heptapeptide from the intact, Cgamma3 domain resulted in a fragment not only showing a greater exposure of aromatic residues but also having the ability to bind Clq. Our data suggest that the structural requirements for C1Q binding may be quite commonplace within Fc, but tertiary folding limits their expression except in Cgamma2 in the native molecule. The solvent perturbation observed with Fc was somewhat lower than would have been expected from the results with the isolated domains, suggesting that interdomain interactions may result in burial of aromatic residues.", "contents": "Correlation between the exposure of aromatic chromophores at the surface of the Fc domains of immunoglobulin G and their ability to bind complement. The recognition that certain biological effector functions associated with the Fc region of human IgG are mediated exclusively by either the Cgamma2 or Cgamma3 domains prompted a study of some of the physical properties of the isolated domains in an attempt to correlate these with functional differentiation. The degree of aromatic chromophore exposure of intact Fc and fragments corresponding to the Cgamma2 and Cgamma3 domains were determined by solvent perturbation difference spectroscopy using 20% ethylene glycol. For the monomeric Cgamma2 fragment one of the two tryptophans and all four of the tyrosines were exposed to solvent. In the pFc' fragment, which represented a dimer of two intact Cgamma3 domains, an average of 0.4 of the two tryptophans of 3.3 of the five tyrosines per chain were exposed. These data were consistent with the suggested involvement of tryptophan in complement fixation since Cgamma2 binds C1q but pFc' does not. Several fragments derived from the Cgamma3 region had previously been shown to have differing environments for their aromatic side chains from circular dichroism studies. These fragments have now been shown to exhibit different degrees of chromophore exposure to solvent. Removal of the carboxy-termimal heptapeptide from the intact, Cgamma3 domain resulted in a fragment not only showing a greater exposure of aromatic residues but also having the ability to bind Clq. Our data suggest that the structural requirements for C1Q binding may be quite commonplace within Fc, but tertiary folding limits their expression except in Cgamma2 in the native molecule. The solvent perturbation observed with Fc was somewhat lower than would have been expected from the results with the isolated domains, suggesting that interdomain interactions may result in burial of aromatic residues."}
{"id": "PMID:13802", "title": "[Further remarks on histochemistry applied to myodiagnosis: findings of \"type predominance\" (author's transl)].", "content": "Data concerning muscular biopsies (histochemically examined) of three patients affected by Charcot-Marie-Tooth disease, neurogenic atrophy of spondilosic origin and benign congenital hypotonia, are described. The common finding was a histochemical appearence of \"type predominance\". This point and the possible \"neurogenic\" origin of benign congenital hypotonia, are discussed.", "contents": "[Further remarks on histochemistry applied to myodiagnosis: findings of \"type predominance\" (author's transl)]. Data concerning muscular biopsies (histochemically examined) of three patients affected by Charcot-Marie-Tooth disease, neurogenic atrophy of spondilosic origin and benign congenital hypotonia, are described. The common finding was a histochemical appearence of \"type predominance\". This point and the possible \"neurogenic\" origin of benign congenital hypotonia, are discussed."}
{"id": "PMID:13809", "title": "Purification and properties of debranching enzyme from dogfish muscle.", "content": "Glycogen debranching enzyme (4-alpha-glucanotransferase amylo-1,6-glucosidase, EC 2.4.1.25 + 3.2.1.33) was purified 140-fold from dogfish muscle in a rapid, high-yield procedure that takes advantage of a strong binding of the enzyme to glycogen, and its quantitative adsorption to concanavalin A-Sepharose only when the polysaccharide is present. The final product was hrophoresis in the presence and absence of dodecyl sulfate. A molecular weight of 162,000 +/- 5000 was determined by sedimentation equilibrium analysis in good agreement with the value of 160,000 estimated by gel electrophoresis, but a low-sedimentation constant of 6.5 S suggests that the enzyme is asymmetric. The molecule appears to be made up of a single polypeptide chain with no evidence for multiple repeating sequences: it could not be dissociated into smaller fragments by dodecyl sulfate even after complete carboxymethylation; tryptic cleavage of the native protein yielded only two fragments of molecular weight 20,000 and 140,000 without loss of enzymatic activity. The amino acid composition of the enzyme is reported; no covalently bound phosphate or carbohydrate could be detected. All 32 sulfhydryl groups present were titrated with 5,5'-dithiobis(2-nitrobenzoic acid) under denaturing conditions; eight reacted readily in the native enzyme without loss of catalytic activity, while substitution of eight additional ones lowered the activity by 50%. Inactivation was greatly reduced by glycogen; the polysaccharide also influenced markedly the electrophoretic behavior of the enzyme and large filamentous aggregates were formed when solutions of both were mixed. Purified debranching enzyme releases 3 mumol of glucose min-1 mg-1 at 19 degrees C, pH 6.0, from a glycogen limit dextrin and one-tenth this amount when the native polysaccharide is used as substrate; glycogen is quantitatively degraded in the presence of phosphorylase. None of the usual sugar phosphates or nucleotide effectors of glycolysis affected enzymatic activity. No phosphorylation by either dogfish or rabbit skeletal muscle protein kinase or phosphorylase kinase could be demonstrated, nor any direct interaction with phosphorylase as measured by SH-group reactivity, enzymatic activity, or rate of phosphorylase b to a conversion. Purification of the 160,000 molecular weight M-line protein of skeletal muscle resulted in the quantitative removal of debranching enzyme, indicating that the two proteins are different.", "contents": "Purification and properties of debranching enzyme from dogfish muscle. Glycogen debranching enzyme (4-alpha-glucanotransferase amylo-1,6-glucosidase, EC 2.4.1.25 + 3.2.1.33) was purified 140-fold from dogfish muscle in a rapid, high-yield procedure that takes advantage of a strong binding of the enzyme to glycogen, and its quantitative adsorption to concanavalin A-Sepharose only when the polysaccharide is present. The final product was hrophoresis in the presence and absence of dodecyl sulfate. A molecular weight of 162,000 +/- 5000 was determined by sedimentation equilibrium analysis in good agreement with the value of 160,000 estimated by gel electrophoresis, but a low-sedimentation constant of 6.5 S suggests that the enzyme is asymmetric. The molecule appears to be made up of a single polypeptide chain with no evidence for multiple repeating sequences: it could not be dissociated into smaller fragments by dodecyl sulfate even after complete carboxymethylation; tryptic cleavage of the native protein yielded only two fragments of molecular weight 20,000 and 140,000 without loss of enzymatic activity. The amino acid composition of the enzyme is reported; no covalently bound phosphate or carbohydrate could be detected. All 32 sulfhydryl groups present were titrated with 5,5'-dithiobis(2-nitrobenzoic acid) under denaturing conditions; eight reacted readily in the native enzyme without loss of catalytic activity, while substitution of eight additional ones lowered the activity by 50%. Inactivation was greatly reduced by glycogen; the polysaccharide also influenced markedly the electrophoretic behavior of the enzyme and large filamentous aggregates were formed when solutions of both were mixed. Purified debranching enzyme releases 3 mumol of glucose min-1 mg-1 at 19 degrees C, pH 6.0, from a glycogen limit dextrin and one-tenth this amount when the native polysaccharide is used as substrate; glycogen is quantitatively degraded in the presence of phosphorylase. None of the usual sugar phosphates or nucleotide effectors of glycolysis affected enzymatic activity. No phosphorylation by either dogfish or rabbit skeletal muscle protein kinase or phosphorylase kinase could be demonstrated, nor any direct interaction with phosphorylase as measured by SH-group reactivity, enzymatic activity, or rate of phosphorylase b to a conversion. Purification of the 160,000 molecular weight M-line protein of skeletal muscle resulted in the quantitative removal of debranching enzyme, indicating that the two proteins are different."}
{"id": "PMID:13810", "title": "Mechanism of pigeon liver malic enzyme: kinetics, specificity, and half-site stoichiometry of the alkylation of a cysteinyl residue by the substrate-inhibitor bromopyruvate.", "content": "Malic enzyme from pigeon liver is alkylated by the substrate analogue bromopyruvate, resulting in the concomitant loss of its oxidative decarboxylase and oxalacetate decarboxylase activities, but not its ability to reduce alpha-keto acids. The inactivation of oxidative decarboxylase activity follows saturation kinetics, indicating the formation of an enzyme-bromopyruvate complex (K congruent to 8 mM) prior to alkylation. The inactivation is inhibited by metal ions and pyridine nucleotide cofactors. Protection of malic enzyme by the substrates L-malate and pyruvate and the inhibitors tartronate and oxalate requires the presence of the above cofactors, which tighten the binding of these carboxylic acids in accord with the ordered kinetic scheme (Hsu, R. Y., Lardy, H. A., and Cleland, W. W. (1967), J. Biol. Chem. 242, 5315-5322). Bromopyruvate is reduced to L-bromolactate by malic enzyme and is an effective inhibitor of L-malate and pyruvate in the overall reaction. The apparent kinetic constants (90 muM-0.8 mM) are one to two orders of magnitude lower than the half-saturation constant (K) of inactivation, indicating a similar tightening of bromopyruvate binding in the E-NADP+ (NADPH)-Mn2+ (Mg2+)-BP complexes. During alkylation, bromopyruvate interacts initially at the carboxylic acid substrate pocket of the active site, as indicated by the protective effect of substrates and the ability of this compound to form kinetically viable complexes with malic enzyme, particularly as a competitive inhibitor of pyruvate carboxylation with a Ki (90 muM) in the same order as its apparent Michaelis constant of 98 muM. Subsequent alkylation of a cysteinyl residue blocks the C-C bond cleavage step. The incorporation of radioactivity from [14C]bromopyruvate gives a half-site stoichiometry of two carboxyketomethyl residues per tetramer, indicating strong negative cooperativity between the four subunits of equal size, or alternatively the presence of structurally dissimilar active sites.", "contents": "Mechanism of pigeon liver malic enzyme: kinetics, specificity, and half-site stoichiometry of the alkylation of a cysteinyl residue by the substrate-inhibitor bromopyruvate. Malic enzyme from pigeon liver is alkylated by the substrate analogue bromopyruvate, resulting in the concomitant loss of its oxidative decarboxylase and oxalacetate decarboxylase activities, but not its ability to reduce alpha-keto acids. The inactivation of oxidative decarboxylase activity follows saturation kinetics, indicating the formation of an enzyme-bromopyruvate complex (K congruent to 8 mM) prior to alkylation. The inactivation is inhibited by metal ions and pyridine nucleotide cofactors. Protection of malic enzyme by the substrates L-malate and pyruvate and the inhibitors tartronate and oxalate requires the presence of the above cofactors, which tighten the binding of these carboxylic acids in accord with the ordered kinetic scheme (Hsu, R. Y., Lardy, H. A., and Cleland, W. W. (1967), J. Biol. Chem. 242, 5315-5322). Bromopyruvate is reduced to L-bromolactate by malic enzyme and is an effective inhibitor of L-malate and pyruvate in the overall reaction. The apparent kinetic constants (90 muM-0.8 mM) are one to two orders of magnitude lower than the half-saturation constant (K) of inactivation, indicating a similar tightening of bromopyruvate binding in the E-NADP+ (NADPH)-Mn2+ (Mg2+)-BP complexes. During alkylation, bromopyruvate interacts initially at the carboxylic acid substrate pocket of the active site, as indicated by the protective effect of substrates and the ability of this compound to form kinetically viable complexes with malic enzyme, particularly as a competitive inhibitor of pyruvate carboxylation with a Ki (90 muM) in the same order as its apparent Michaelis constant of 98 muM. Subsequent alkylation of a cysteinyl residue blocks the C-C bond cleavage step. The incorporation of radioactivity from [14C]bromopyruvate gives a half-site stoichiometry of two carboxyketomethyl residues per tetramer, indicating strong negative cooperativity between the four subunits of equal size, or alternatively the presence of structurally dissimilar active sites."}
{"id": "PMID:13811", "title": "Mechanism of mitochondrial carbamoyl-phosphate synthetase: synthesis and properties of active CO2, precursor of carbamoyl phosphate.", "content": "This paper demonstrates the formation of \"active CO2\" (CO2-P), a precursor of carbamoyl phosphate (CP), with frog liver carbamoyl-phosphate synthetase. Absence of ammonia is essential for the demonstration by pulse incubation with H14CO3- of CO2-P. Adenosine triphosphate (ATP) and acetylglutamate are required for the synthesis of CO2-P, which is highly unstable in aqueous solutions (t1/2 = 0.75 s at 24 degrees C at neutral pH). In the absence of ammonia, CO2-P attains rapidly a steady-state level, which depends on the concentration of ATP and HCO3-. The \"apparent KM'S\" are approximately equal to those found for the adenosine triphosphate (ATPase) activity of the enzyme. The maximum level of CO2-P is limited by the amount of enzyme, and approximates 4 mol of intermediate/mol of enzyme. The unprotonated form of ammonia seems to be the species reacting with CO2-P to produce CP. The reaction of CO2-P and NH3 is very fast (rate constant kn = 8 x 10(4) M-1 S-1) and does not consume free ATP. Therefore, the 2 mol of ATP necessary for CP synthesis binds or reacts with the enzyme and/or CO2 prior to reaction with NH3. The reaction of CO2-P with NH3 also takes place in acetone under conditions at which the enzyme is not active, suggesting little or no assistance from enzyme catalysis or that a part of the catalytic site is \"frozen\" by the solvent in the active conformation. In the light of these and other findings, a new scheme is proposed for the mechanism of frog liver carbamoyl-phosphate synthetase and some considerations are made on the chemical nature of the intermediate and on the possible evolutionary significance of the reaction of CO2-P with NH3 in acetone.", "contents": "Mechanism of mitochondrial carbamoyl-phosphate synthetase: synthesis and properties of active CO2, precursor of carbamoyl phosphate. This paper demonstrates the formation of \"active CO2\" (CO2-P), a precursor of carbamoyl phosphate (CP), with frog liver carbamoyl-phosphate synthetase. Absence of ammonia is essential for the demonstration by pulse incubation with H14CO3- of CO2-P. Adenosine triphosphate (ATP) and acetylglutamate are required for the synthesis of CO2-P, which is highly unstable in aqueous solutions (t1/2 = 0.75 s at 24 degrees C at neutral pH). In the absence of ammonia, CO2-P attains rapidly a steady-state level, which depends on the concentration of ATP and HCO3-. The \"apparent KM'S\" are approximately equal to those found for the adenosine triphosphate (ATPase) activity of the enzyme. The maximum level of CO2-P is limited by the amount of enzyme, and approximates 4 mol of intermediate/mol of enzyme. The unprotonated form of ammonia seems to be the species reacting with CO2-P to produce CP. The reaction of CO2-P and NH3 is very fast (rate constant kn = 8 x 10(4) M-1 S-1) and does not consume free ATP. Therefore, the 2 mol of ATP necessary for CP synthesis binds or reacts with the enzyme and/or CO2 prior to reaction with NH3. The reaction of CO2-P with NH3 also takes place in acetone under conditions at which the enzyme is not active, suggesting little or no assistance from enzyme catalysis or that a part of the catalytic site is \"frozen\" by the solvent in the active conformation. In the light of these and other findings, a new scheme is proposed for the mechanism of frog liver carbamoyl-phosphate synthetase and some considerations are made on the chemical nature of the intermediate and on the possible evolutionary significance of the reaction of CO2-P with NH3 in acetone."}
{"id": "PMID:13812", "title": "PH-induced changes in the reactions controlled by the low- and high-affinity Ca2+-binding sites in sarcoplasmic reticulum.", "content": "The effect of pH on the Ca2+-binding sites of high and low affinity, located respectively on the outer and inner surfaces of the sarcoplasmic reticulum membrane, was investigated using intact and leaky sarcoplasmic reticulum vesicles. With the use of intact vesicles, different pH profiles of membrane phosphorylation and rates of nucleoside triphosphate hydrolysis were obtained depending on the assay temperature, on the Ca2+ concentration, and on whether ATP or ITP was used as substrate. The different pH profiles were related to the amount of Ca2+ accumualted by the vesicles, i.e., to different degrees of saturation of the inner, low-affinity Ca2+-binding site. With the use of leaky vesicles, the saturation of the two Ca2+-binding sites could be controlled more precisely since the Ca2+ concentration on both sides of the membrane was equal to the Ca2+ concentration of the assay medium. Using leaky vesicles and measuring the rates of nucleotide hydrolysis, nucleotide-phosphate exchange and membrane phosphorylation by nucleotide as an indication of the degree of saturation of the Ca2+-binding sites, we observed that the affinity of both the high- and low-affinity sites increased three to four orders of magnitude when the pH of the assay medium was increased from 6.1 to 8.65.", "contents": "PH-induced changes in the reactions controlled by the low- and high-affinity Ca2+-binding sites in sarcoplasmic reticulum. The effect of pH on the Ca2+-binding sites of high and low affinity, located respectively on the outer and inner surfaces of the sarcoplasmic reticulum membrane, was investigated using intact and leaky sarcoplasmic reticulum vesicles. With the use of intact vesicles, different pH profiles of membrane phosphorylation and rates of nucleoside triphosphate hydrolysis were obtained depending on the assay temperature, on the Ca2+ concentration, and on whether ATP or ITP was used as substrate. The different pH profiles were related to the amount of Ca2+ accumualted by the vesicles, i.e., to different degrees of saturation of the inner, low-affinity Ca2+-binding site. With the use of leaky vesicles, the saturation of the two Ca2+-binding sites could be controlled more precisely since the Ca2+ concentration on both sides of the membrane was equal to the Ca2+ concentration of the assay medium. Using leaky vesicles and measuring the rates of nucleotide hydrolysis, nucleotide-phosphate exchange and membrane phosphorylation by nucleotide as an indication of the degree of saturation of the Ca2+-binding sites, we observed that the affinity of both the high- and low-affinity sites increased three to four orders of magnitude when the pH of the assay medium was increased from 6.1 to 8.65."}
{"id": "PMID:13813", "title": "Investigation of the open ring form of nicotinamide adenine dinucleotide.", "content": "In strong alkali, nicotinamide adenine dinucleotide (NAD+) undergoes a ring opening of the nicotinamide ring. The open form of NAD+, ONAD, has two pKa values at--1.9 and 11.2 and absorbs maximally at 350 nm in its acidic form, at 372 nm in its neutral form, and at 340 nm in its aniomic form. ONAD has the chemical properties expected for a Schiff base of 2-carboxamideglutacondialdehyde (CGDA) and adenosine diphosphate ribosylamine. The decomposition of ONAD has been studied over a wide range of pH. A final product of ONAD hydrolysis is the base fluorescent compound 2-hydroxynicotinaldehyde. In the pH range 10--13, CGDA can be trapped as an intermediate, which absorbs maximally at 345 nm in its anionic form and at 320 nm in its neutral form, pKa = 2.9. The yield of 2-hydroxynicotinaldehyde from ONAD has been estimated as 95% at NaOH concentrations of 5 N and above, and is postulated to result from ring closure of CGDA. The pseudobase hydroxide ring addition adduct of NAD+, psiNAD-OH, is reversibly formed from NAD+ and is the 370-nm precursor of ONAD.", "contents": "Investigation of the open ring form of nicotinamide adenine dinucleotide. In strong alkali, nicotinamide adenine dinucleotide (NAD+) undergoes a ring opening of the nicotinamide ring. The open form of NAD+, ONAD, has two pKa values at--1.9 and 11.2 and absorbs maximally at 350 nm in its acidic form, at 372 nm in its neutral form, and at 340 nm in its aniomic form. ONAD has the chemical properties expected for a Schiff base of 2-carboxamideglutacondialdehyde (CGDA) and adenosine diphosphate ribosylamine. The decomposition of ONAD has been studied over a wide range of pH. A final product of ONAD hydrolysis is the base fluorescent compound 2-hydroxynicotinaldehyde. In the pH range 10--13, CGDA can be trapped as an intermediate, which absorbs maximally at 345 nm in its anionic form and at 320 nm in its neutral form, pKa = 2.9. The yield of 2-hydroxynicotinaldehyde from ONAD has been estimated as 95% at NaOH concentrations of 5 N and above, and is postulated to result from ring closure of CGDA. The pseudobase hydroxide ring addition adduct of NAD+, psiNAD-OH, is reversibly formed from NAD+ and is the 370-nm precursor of ONAD."}
{"id": "PMID:13814", "title": "Metal site conformational states of vanadyl(IV) human serotransferrin complexes.", "content": "This study was undertaken to investigate the conformational states of the two metal sites in the human serum transferrin molecule. The 9.2 GHz electron paramagnetic resonance spectra of frozen solutions of divanadyl(IV) transferrin consist of a superposition of two sets of resonances, A and B, due to the magnetically nonequivalent binding environments of the VO2+ ion. Examination of the intensities of the A and B resonances as a function of pH from 6.0 to 10.7 reveals that they arise from two conformational states of the metal sites in which the geometrical arrangement and/or identity of one or more ligands in the first coordination sphere are different. From pH 7.5 to 9.0, the metal sites exist in A and B conformations but above pH 9.0 the A conformation. This transformation is coupled to the ionization of an apparently noncoordinating protein functional group with a pK - 10.0 +/- 0.1. Below pH 7.0, binding in the B conformation is rapidly lost, driven in part by the protonation of a functional group, possibly the anion, with a pK - 6.6 +/- 0.1. In 90% D2O, this pK is elevated to 7.8 +/- 0.1. At pH 6.0 in H2O, essentially one VO2+ ion remains bound to the protein with the metal site in the A conformation. Experiments with mixed VO2+ -Fe3+ transferrin complexes indicate that the same may be true of Fe3+. At pH 10.7, a new set of VO2+ resonances, labeled C, are observed; they possibly arise from a third conformation of the metal site. One bicarbonate or corbonate is required per VO2+ ion bound to the protein. 2.7 H+ are released per VO2+ bound in either the A or B conformations. The above results are discussed in terms of the \"equivalence\" and \"nonequivalence\" of the metal sites.", "contents": "Metal site conformational states of vanadyl(IV) human serotransferrin complexes. This study was undertaken to investigate the conformational states of the two metal sites in the human serum transferrin molecule. The 9.2 GHz electron paramagnetic resonance spectra of frozen solutions of divanadyl(IV) transferrin consist of a superposition of two sets of resonances, A and B, due to the magnetically nonequivalent binding environments of the VO2+ ion. Examination of the intensities of the A and B resonances as a function of pH from 6.0 to 10.7 reveals that they arise from two conformational states of the metal sites in which the geometrical arrangement and/or identity of one or more ligands in the first coordination sphere are different. From pH 7.5 to 9.0, the metal sites exist in A and B conformations but above pH 9.0 the A conformation. This transformation is coupled to the ionization of an apparently noncoordinating protein functional group with a pK - 10.0 +/- 0.1. Below pH 7.0, binding in the B conformation is rapidly lost, driven in part by the protonation of a functional group, possibly the anion, with a pK - 6.6 +/- 0.1. In 90% D2O, this pK is elevated to 7.8 +/- 0.1. At pH 6.0 in H2O, essentially one VO2+ ion remains bound to the protein with the metal site in the A conformation. Experiments with mixed VO2+ -Fe3+ transferrin complexes indicate that the same may be true of Fe3+. At pH 10.7, a new set of VO2+ resonances, labeled C, are observed; they possibly arise from a third conformation of the metal site. One bicarbonate or corbonate is required per VO2+ ion bound to the protein. 2.7 H+ are released per VO2+ bound in either the A or B conformations. The above results are discussed in terms of the \"equivalence\" and \"nonequivalence\" of the metal sites."}
{"id": "PMID:13815", "title": "Isolation, characterization, and activation of the magnesium dependent endodeoxyribonuclease from Bacillus subtilis.", "content": "A major endodeoxyribonulcease was isolated from a mutant of the transformable Bacillus subtilis 168. The magnesium-dependent endonuclease was purified approximately 750-fold to electrophoretic homogeneity. The enzyme had a molecular weight of about 31 000, as determined by gel filtration and polyacrylamide gel electrophoresis. The protein appears to be composed of two subunits. The nuclease was dependent on magnesium or maganese ions for hydrolytic activity. The purified nuclease degraded DNA from several  species of Bacillus, as well as Escherichia coli DNA, alkylated, depurinated, and thymine-dimer containing B. subtilis DNA, and hydroxymethyluracil-containing phage DNA. The enzyme also hydrolyzed single-stranded DNA, although native DNA was the preferred substrate. However, the nuclease was unable to degrade ribosomal RNA. The cleavage products of the DNA hydrolysis have 5'-phosphate and 3'-hydroxyl ends. The enzyme could be activated in crude extracts by heat treatment or treatment with guanidine hydrochloride. The nuclease activity was inhibited by phosphate and by high concentrations of NaCl. A possible function for this endonuclease in bacterial transformation is discussed.", "contents": "Isolation, characterization, and activation of the magnesium dependent endodeoxyribonuclease from Bacillus subtilis. A major endodeoxyribonulcease was isolated from a mutant of the transformable Bacillus subtilis 168. The magnesium-dependent endonuclease was purified approximately 750-fold to electrophoretic homogeneity. The enzyme had a molecular weight of about 31 000, as determined by gel filtration and polyacrylamide gel electrophoresis. The protein appears to be composed of two subunits. The nuclease was dependent on magnesium or maganese ions for hydrolytic activity. The purified nuclease degraded DNA from several  species of Bacillus, as well as Escherichia coli DNA, alkylated, depurinated, and thymine-dimer containing B. subtilis DNA, and hydroxymethyluracil-containing phage DNA. The enzyme also hydrolyzed single-stranded DNA, although native DNA was the preferred substrate. However, the nuclease was unable to degrade ribosomal RNA. The cleavage products of the DNA hydrolysis have 5'-phosphate and 3'-hydroxyl ends. The enzyme could be activated in crude extracts by heat treatment or treatment with guanidine hydrochloride. The nuclease activity was inhibited by phosphate and by high concentrations of NaCl. A possible function for this endonuclease in bacterial transformation is discussed."}
{"id": "PMID:13816", "title": "Mechanism of lysozyme catalysis: role of ground-state strain in subsite D in hen egg-white and human lysozymes.", "content": "The association constants for the binding of various saccharides to hen egg-white lysozyme and human lysozyme have been measured by fluorescence titration. Among these are the oligosaccharides GlcNAc-beta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-GlcNAc, GlcNAc-beta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-N-acetyl-D-xylosamine, and GlcNAc-beta(1 leads to 4-GlcNAc-beta(1 leads to 4)-MurNAc, prepared here for the first time. The binding constants for saccharides which must have N-acetylmuramic acid, N-acetyl-D-glucosamine, or N-acetyl-D-xylosamine bound in subsite D indicate that there is no strain involved in the binding of N-acetyl-D-glycosamine in this site, and that the lactyl group of N-acetylmuramic acid (rather than the hydroxymethyl group) is responsible for the apparent strain previously reported for binding at this subsite. For hen egg-white lysozyme, the dependence of saccharide binding on pH or on a saturating concentration of Gd(III) suggests that the conformation of several of the complexes are different from one another and from that proposed for a productive complex. This is supported by fluorescence difference spectra of the various hen egg-white lysozyme-saccharide complexes. Human lysozyme binds most saccharides studied more weakly than the hen egg-white enzyme, but binds GlcNAc-beta(1 leads to 4)-MurNAc-beta(1leads to 4)-GlcNAc-beta(1 leads to 4)-MurNAc more strongly. It is suggested that subsite C of the human enzyme is \"looser\" than the equivalent site in the hen egg enzyme, so that the rearrangement of a saccharide in this subsite in response to introduction of an N-acetylmuramic acid residue into subsite D destabilizes the saccharide complexes of human lysozyme less than it does the corresponding hen egg-white lysozyme complexes. This difference and the differences in the fluorescence difference spectra of hen egg-white lysozyme and human lysozyme are ascribed mainly to the replacement of Trp-62 in hen egg-white lysozyme by Tyr-63 in the human enzyme. The implications of our findings for the assumption of superposition and additivity of energies of binding in individual subsites, and for the estimation of the role of strain in lysozyme catalysis, are discussed.", "contents": "Mechanism of lysozyme catalysis: role of ground-state strain in subsite D in hen egg-white and human lysozymes. The association constants for the binding of various saccharides to hen egg-white lysozyme and human lysozyme have been measured by fluorescence titration. Among these are the oligosaccharides GlcNAc-beta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-GlcNAc, GlcNAc-beta(1 leads to 4)-MurNAc-beta(1 leads to 4)-GlcNAc-beta(1 leads to 4)-N-acetyl-D-xylosamine, and GlcNAc-beta(1 leads to 4-GlcNAc-beta(1 leads to 4)-MurNAc, prepared here for the first time. The binding constants for saccharides which must have N-acetylmuramic acid, N-acetyl-D-glucosamine, or N-acetyl-D-xylosamine bound in subsite D indicate that there is no strain involved in the binding of N-acetyl-D-glycosamine in this site, and that the lactyl group of N-acetylmuramic acid (rather than the hydroxymethyl group) is responsible for the apparent strain previously reported for binding at this subsite. For hen egg-white lysozyme, the dependence of saccharide binding on pH or on a saturating concentration of Gd(III) suggests that the conformation of several of the complexes are different from one another and from that proposed for a productive complex. This is supported by fluorescence difference spectra of the various hen egg-white lysozyme-saccharide complexes. Human lysozyme binds most saccharides studied more weakly than the hen egg-white enzyme, but binds GlcNAc-beta(1 leads to 4)-MurNAc-beta(1leads to 4)-GlcNAc-beta(1 leads to 4)-MurNAc more strongly. It is suggested that subsite C of the human enzyme is \"looser\" than the equivalent site in the hen egg enzyme, so that the rearrangement of a saccharide in this subsite in response to introduction of an N-acetylmuramic acid residue into subsite D destabilizes the saccharide complexes of human lysozyme less than it does the corresponding hen egg-white lysozyme complexes. This difference and the differences in the fluorescence difference spectra of hen egg-white lysozyme and human lysozyme are ascribed mainly to the replacement of Trp-62 in hen egg-white lysozyme by Tyr-63 in the human enzyme. The implications of our findings for the assumption of superposition and additivity of energies of binding in individual subsites, and for the estimation of the role of strain in lysozyme catalysis, are discussed."}
{"id": "PMID:13817", "title": "Energetics of the cooperative and noncooperative binding of nicotinamide adenine dinucleotide to yeast glyceraldehyde-3-phosphate dehydrogenase at pH 6.5 and pH 8.5. Equilibrium and calorimetric analysis over a range of temperature.", "content": "The binding of nicotinamide adenine dinucleotide (NAD+) to yeast glyceraldehyde-3-phosphate dehydrogenase (GPDH) has been studied at pH 6.5 and 8.5, at 5,25, and 40 degrees C, by calorimetry, fluorometry, spectrophotometry, equilibrium dialysis, and flow dialysis. As reported earlier for pH 7.3 (Velick S.F., Baggott, J.P., and Sturtevant, J.M. (1971), Biochemistry 10, 779), the binding is accompanied by enthalpy changes which become rapidly more negative as the temperature increases, with delta Cp = -500 to -750 cal deg-1 (mole of NAD+ bound)-1, and by entropy changes which also, as required by the large negative delta Cp, become rapidly more negative with increasing temperature. The binding data at pH 6.5 can be fitted on the basis of either four identical noninteracting sites, or of four sites showing a small degree of negative cooperativity. The data at pH 8.5, particularly at 40 degrees C, require the introduction of positive cooperativity, as was previously shown by Kirschner et al. (Kirschner, K., Eigen, M., Bittman, R., and Voigt, B. (1966), Proc. Natl. Acad. Sci. U.S.A. 56, 1661), and can be equally well fitted on the basis of a sequential model (Adair, G.S. (1925), J. Biol. Chem. 63, 529) or a concerted model (Monod, J., Wyman, J., and Changeux, J.P. (1965), J. Mol. Biol. 12, 88). It is proposed that the observed thermodynamic changes are largely the result of a hydrophobic effect due to a decrease in the exposure of nonpolar groups to the solvent, and of a tightening of the protein structure when the coenzyme is bound with concomitant decrease in the number of easily excitable internal degrees of freedom.", "contents": "Energetics of the cooperative and noncooperative binding of nicotinamide adenine dinucleotide to yeast glyceraldehyde-3-phosphate dehydrogenase at pH 6.5 and pH 8.5. Equilibrium and calorimetric analysis over a range of temperature. The binding of nicotinamide adenine dinucleotide (NAD+) to yeast glyceraldehyde-3-phosphate dehydrogenase (GPDH) has been studied at pH 6.5 and 8.5, at 5,25, and 40 degrees C, by calorimetry, fluorometry, spectrophotometry, equilibrium dialysis, and flow dialysis. As reported earlier for pH 7.3 (Velick S.F., Baggott, J.P., and Sturtevant, J.M. (1971), Biochemistry 10, 779), the binding is accompanied by enthalpy changes which become rapidly more negative as the temperature increases, with delta Cp = -500 to -750 cal deg-1 (mole of NAD+ bound)-1, and by entropy changes which also, as required by the large negative delta Cp, become rapidly more negative with increasing temperature. The binding data at pH 6.5 can be fitted on the basis of either four identical noninteracting sites, or of four sites showing a small degree of negative cooperativity. The data at pH 8.5, particularly at 40 degrees C, require the introduction of positive cooperativity, as was previously shown by Kirschner et al. (Kirschner, K., Eigen, M., Bittman, R., and Voigt, B. (1966), Proc. Natl. Acad. Sci. U.S.A. 56, 1661), and can be equally well fitted on the basis of a sequential model (Adair, G.S. (1925), J. Biol. Chem. 63, 529) or a concerted model (Monod, J., Wyman, J., and Changeux, J.P. (1965), J. Mol. Biol. 12, 88). It is proposed that the observed thermodynamic changes are largely the result of a hydrophobic effect due to a decrease in the exposure of nonpolar groups to the solvent, and of a tightening of the protein structure when the coenzyme is bound with concomitant decrease in the number of easily excitable internal degrees of freedom."}
{"id": "PMID:13818", "title": "Interaction of acetazolamide and 4-nitrothiophenolate ion with bivalent metal ion derivatives of bovine carbonic anhydrase.", "content": "The stability and rate constants for the interaction of acetazolamide (diamox) and 4-nitrothiophenolate ion (NTP) with the bivalent Mn, Co, Ni, Cu and Cd forms of bovine carbonic anhydrase have been measured by utilizing the distinct visible spectra of each metalloenzyme-NTP adduct. Differing stabilities of the various NTP and (particularly) diamox complexes reside mainly in varying values for the dissociation rate constants (kd). Intrinsic formation rate constants (for the acid form of the enzyme reacting with the basic form of the ligand) are uniformly high (greater than or equal 2 X 10(7) M-1 s-1 at 25 degrees C). Invariance of kd with pH and a bell-shaped log K-pH profile with the Cu-enzyme adducts are features observed previously with the native enzyme. Binding of NTP with the Cu and Cd metalloenzymes is stronger than to the native form.", "contents": "Interaction of acetazolamide and 4-nitrothiophenolate ion with bivalent metal ion derivatives of bovine carbonic anhydrase. The stability and rate constants for the interaction of acetazolamide (diamox) and 4-nitrothiophenolate ion (NTP) with the bivalent Mn, Co, Ni, Cu and Cd forms of bovine carbonic anhydrase have been measured by utilizing the distinct visible spectra of each metalloenzyme-NTP adduct. Differing stabilities of the various NTP and (particularly) diamox complexes reside mainly in varying values for the dissociation rate constants (kd). Intrinsic formation rate constants (for the acid form of the enzyme reacting with the basic form of the ligand) are uniformly high (greater than or equal 2 X 10(7) M-1 s-1 at 25 degrees C). Invariance of kd with pH and a bell-shaped log K-pH profile with the Cu-enzyme adducts are features observed previously with the native enzyme. Binding of NTP with the Cu and Cd metalloenzymes is stronger than to the native form."}
{"id": "PMID:13819", "title": "Thermodynamic and conformational studies on an immunoglobulin light chain which reversibly precipitates at low temperatures.", "content": "A lambda light chain, isolated from an immunoglobulin G molecule, was found to reversibly precipitate at low temperatures. This cryoprecipitation was a function of pH, ionic strength, protein concentration, and time as well as temperature. The lambda chain underwent a cooperative conformational change as the temperature was lowered from 26 to 0 degrees C as judged by ultraviolet difference spectroscopy and circular dichroism. Normal lambda chains showed no conformational change. By difference spectroscopy it was possible to calculate the equilibrium constant governing the conformational change. The  change was strongly exothermic (delta H approximately -80 kcal mol-1) and accompanied by a large decrease in entropy (delta S approximately -280 eu). The midpoint of the transition was dependent on the initial protein concentration, suggesting that only the noncovalent dimer of the lambda chain exhibited the conformational change. The existence of a monomer-dimer eqiulibrium (KA approximately 4 X 10(5) M-1) was confirmed by sedimentation velocity. No conformational change was observed by circular dichroism at concentrations where greater than 95% of lambda chain was in the form of a monomer. Although high ionic strength inhibited cryoprecipitation, it had no effect on the conformational change. Stabilization of the dimer by forming an interchain disulfide bond between two monomers abolished both the conformational change and cryoprecipitation. A fragment corresponding to the constant region was isolated from both peptic and tryptic digests of the lambda chain. This fragment neither cryoprecipitated nor showed temperature dependence conformational changes. It proved impossible to isolate a fragment corresponding to the variable region. Both qualitative and quantitative models are presented to account for the behavior of the lambda chain at low temperatures.", "contents": "Thermodynamic and conformational studies on an immunoglobulin light chain which reversibly precipitates at low temperatures. A lambda light chain, isolated from an immunoglobulin G molecule, was found to reversibly precipitate at low temperatures. This cryoprecipitation was a function of pH, ionic strength, protein concentration, and time as well as temperature. The lambda chain underwent a cooperative conformational change as the temperature was lowered from 26 to 0 degrees C as judged by ultraviolet difference spectroscopy and circular dichroism. Normal lambda chains showed no conformational change. By difference spectroscopy it was possible to calculate the equilibrium constant governing the conformational change. The  change was strongly exothermic (delta H approximately -80 kcal mol-1) and accompanied by a large decrease in entropy (delta S approximately -280 eu). The midpoint of the transition was dependent on the initial protein concentration, suggesting that only the noncovalent dimer of the lambda chain exhibited the conformational change. The existence of a monomer-dimer eqiulibrium (KA approximately 4 X 10(5) M-1) was confirmed by sedimentation velocity. No conformational change was observed by circular dichroism at concentrations where greater than 95% of lambda chain was in the form of a monomer. Although high ionic strength inhibited cryoprecipitation, it had no effect on the conformational change. Stabilization of the dimer by forming an interchain disulfide bond between two monomers abolished both the conformational change and cryoprecipitation. A fragment corresponding to the constant region was isolated from both peptic and tryptic digests of the lambda chain. This fragment neither cryoprecipitated nor showed temperature dependence conformational changes. It proved impossible to isolate a fragment corresponding to the variable region. Both qualitative and quantitative models are presented to account for the behavior of the lambda chain at low temperatures."}
{"id": "PMID:13820", "title": "Determination of the rate-limiting steps for malic enzyme by the use of isotope effects and other kinetic studies.", "content": "Isotope effects have been measured with Mg2+ as the activator and L-malate labeled with deuterium or tritium at carbon 2 as the substrate over the pH range 4-10. Comparison of the nearly pH-independent deuterium-isotope effect on V/Kmalate of 1.5 with the tritium effect of 2.0 by the method of Northrop (Northrop, D.B. (1975), Biochemistry 14, 2644) gives limits on the true effect of deuterium substitution on the bond-breaking step of 5-8 in the forward reaction and 4-6.5 in the reverse direction. Comparison of the deuterium effect on V/K with the 13C-isotope effect of 1.031 reported by Schimerlik et al. (Schimerlik, M.I., Rife, J.E., and Cleland, W.W. (1975), Biochemistry 14, 5347) allows the deduction that at pH 8 reverse hydride transfer is six to eight times faster than decarboxylation, which is thus largely rate limiting for the catalytic reaction. The absence of a deuterium-isotope effect on V at pH 7-8 and comparison of the Ki of pyruvate as an uncompetitive inhibitor of the forward reaction and a substrate for the reverse reaction indicate that at neutral pH the release of TPNH from enzyme-reduced triphosphopyridine nucleotide (E-TPNH) is the rate-limiting step in the forward direction. The observation of a deuterium effect on V that approaches 3 at pH 4 and 10 shows, however, that, at very low and very high pH, hydride transfer may become partly rate limiting. In the reverse reaction, the probable rate-limiting step at pH 7 is the isomerization of E-TPNH, while at pH 8.5 and above V becomes too large to measure and appears infinite. Substitution of Co2+, Ni2+, or low levels of Mn2+ for Mg2+ gives similar deuterium-isotope effects, although the values of V and Kmalate vary considerably with metal. The kinetics of Mn2+ show pronounced negative cooperativity, with Km values of 7 muM and 5 mM for concentration ranges from 4 to 100 muM and over 1 mM.", "contents": "Determination of the rate-limiting steps for malic enzyme by the use of isotope effects and other kinetic studies. Isotope effects have been measured with Mg2+ as the activator and L-malate labeled with deuterium or tritium at carbon 2 as the substrate over the pH range 4-10. Comparison of the nearly pH-independent deuterium-isotope effect on V/Kmalate of 1.5 with the tritium effect of 2.0 by the method of Northrop (Northrop, D.B. (1975), Biochemistry 14, 2644) gives limits on the true effect of deuterium substitution on the bond-breaking step of 5-8 in the forward reaction and 4-6.5 in the reverse direction. Comparison of the deuterium effect on V/K with the 13C-isotope effect of 1.031 reported by Schimerlik et al. (Schimerlik, M.I., Rife, J.E., and Cleland, W.W. (1975), Biochemistry 14, 5347) allows the deduction that at pH 8 reverse hydride transfer is six to eight times faster than decarboxylation, which is thus largely rate limiting for the catalytic reaction. The absence of a deuterium-isotope effect on V at pH 7-8 and comparison of the Ki of pyruvate as an uncompetitive inhibitor of the forward reaction and a substrate for the reverse reaction indicate that at neutral pH the release of TPNH from enzyme-reduced triphosphopyridine nucleotide (E-TPNH) is the rate-limiting step in the forward direction. The observation of a deuterium effect on V that approaches 3 at pH 4 and 10 shows, however, that, at very low and very high pH, hydride transfer may become partly rate limiting. In the reverse reaction, the probable rate-limiting step at pH 7 is the isomerization of E-TPNH, while at pH 8.5 and above V becomes too large to measure and appears infinite. Substitution of Co2+, Ni2+, or low levels of Mn2+ for Mg2+ gives similar deuterium-isotope effects, although the values of V and Kmalate vary considerably with metal. The kinetics of Mn2+ show pronounced negative cooperativity, with Km values of 7 muM and 5 mM for concentration ranges from 4 to 100 muM and over 1 mM."}
{"id": "PMID:13821", "title": "pH variation of the kinetic parameters and the catalytic mechanism of malic enzyme.", "content": "The pH variation of the kinetic parameters for the oxidative decarboxylation of L-malate and decarboxylation of oxalacetate catalyzed by malic enzyme has been used to gain information on the catalytic mechanism of this enzyme. With Mn2+ as the activator, an active-site residue with a pK of 5.4 must be protonated for oxalacetate decarboxylation and ionized for the oxidative decarboxylation of L-malate. With Mg2+ as the metal, this pK is 6, and, at high pH, V/K for L-malate decreases when groups with pKs of 7.8 and 9 are deprotonated. The group at 7.8 is a neutral acid (thought to be water coordinated to Mg2+), while the group at 9 is a cationic acid such as lysine. The V profile for reaction of malate shows these pKs displaced outward by 1.4 pH units, since the rate-limiting step is normally TPNH release, and the chemical reaction, which is pH sensitive, is 25 times faster. TPN binding is decreased by ionization of a group with pK 9.3 or protonation of a group with pK 5.3. The pH variation of the Km for Mg shows that protonation of a group with pK 8.7 (possibly SH) decreases metal binding in the presence of malate by a factor of 1400, and in the absence of malate by a factor of 20. A catalytic mechanism is proposed in which hydride transfer is accompanied by transfer of a proton to the group with pK 5.4-6, and enolpyruvate is protonated by water coordinated to the Mg2+ (pK 7.8) after decarboxylation and release of CO2.", "contents": "pH variation of the kinetic parameters and the catalytic mechanism of malic enzyme. The pH variation of the kinetic parameters for the oxidative decarboxylation of L-malate and decarboxylation of oxalacetate catalyzed by malic enzyme has been used to gain information on the catalytic mechanism of this enzyme. With Mn2+ as the activator, an active-site residue with a pK of 5.4 must be protonated for oxalacetate decarboxylation and ionized for the oxidative decarboxylation of L-malate. With Mg2+ as the metal, this pK is 6, and, at high pH, V/K for L-malate decreases when groups with pKs of 7.8 and 9 are deprotonated. The group at 7.8 is a neutral acid (thought to be water coordinated to Mg2+), while the group at 9 is a cationic acid such as lysine. The V profile for reaction of malate shows these pKs displaced outward by 1.4 pH units, since the rate-limiting step is normally TPNH release, and the chemical reaction, which is pH sensitive, is 25 times faster. TPN binding is decreased by ionization of a group with pK 9.3 or protonation of a group with pK 5.3. The pH variation of the Km for Mg shows that protonation of a group with pK 8.7 (possibly SH) decreases metal binding in the presence of malate by a factor of 1400, and in the absence of malate by a factor of 20. A catalytic mechanism is proposed in which hydride transfer is accompanied by transfer of a proton to the group with pK 5.4-6, and enolpyruvate is protonated by water coordinated to the Mg2+ (pK 7.8) after decarboxylation and release of CO2."}
{"id": "PMID:13822", "title": "Effect of magnesium on the properties of zinc alkaline phosphatase.", "content": "Alkaline phosphatase of Escherichia coli, isolated by procedures which do not alter its intrinsic metal content, contains 4.0 +/- 0.3 g-atoms of tightly bound zinc per mole (Kd less than 1 muM) and 1.3 +/- 0.2 g-atoms of magnesium per mole (Bosron, W.F., Kennedy, F.S., and Vallee, B.L. (1975), Biochemistry 14, 2275-2282). Importantly, the binding of magnesium is dependent both upon pH and zinc content. Hence, the failure to assign the maximal magnesium stoichiometry to enzyme isolated by conventional procedures may be considered a consequence of the conditions chosen for optimal bacterial growth and purification of the enzyme which are not the conditions for optimal binding of magnesium to alkaline phosphatase. Under the conditions employed for the present experimental studies, a maximum of six metal sites are available to bind zinc and magnesium, i.e., four for zinc and two for magnesium. Magnesium alone does not activate the apoenzyme, but it regulates the nature of the zinc-dependent restoration of catalytic activity to apophosphatase, increasing the activity of enzyme containing 2-g-atoms of zinc five-fold and that of enzyme containing 4-g-atoms of zinc 1.4-fold. Moreover, hydrogen-tritium exchange reveals the stabilizing effects of magnesium on the structural properties of phosphatase. However, neither the KM for substrate nor the phosphate binding stoichiometry and Ki are significantly altered by magnesium. Hence, magnesium, which is specificially bound to the enzyme, both stabilizes the dynamic protein structure and regulates the expression of catalytic activity by zinc in alkaline phosphatase.", "contents": "Effect of magnesium on the properties of zinc alkaline phosphatase. Alkaline phosphatase of Escherichia coli, isolated by procedures which do not alter its intrinsic metal content, contains 4.0 +/- 0.3 g-atoms of tightly bound zinc per mole (Kd less than 1 muM) and 1.3 +/- 0.2 g-atoms of magnesium per mole (Bosron, W.F., Kennedy, F.S., and Vallee, B.L. (1975), Biochemistry 14, 2275-2282). Importantly, the binding of magnesium is dependent both upon pH and zinc content. Hence, the failure to assign the maximal magnesium stoichiometry to enzyme isolated by conventional procedures may be considered a consequence of the conditions chosen for optimal bacterial growth and purification of the enzyme which are not the conditions for optimal binding of magnesium to alkaline phosphatase. Under the conditions employed for the present experimental studies, a maximum of six metal sites are available to bind zinc and magnesium, i.e., four for zinc and two for magnesium. Magnesium alone does not activate the apoenzyme, but it regulates the nature of the zinc-dependent restoration of catalytic activity to apophosphatase, increasing the activity of enzyme containing 2-g-atoms of zinc five-fold and that of enzyme containing 4-g-atoms of zinc 1.4-fold. Moreover, hydrogen-tritium exchange reveals the stabilizing effects of magnesium on the structural properties of phosphatase. However, neither the KM for substrate nor the phosphate binding stoichiometry and Ki are significantly altered by magnesium. Hence, magnesium, which is specificially bound to the enzyme, both stabilizes the dynamic protein structure and regulates the expression of catalytic activity by zinc in alkaline phosphatase."}
{"id": "PMID:13823", "title": "Dissociation and reconstitution of human ferroxidase II.", "content": "The ferroxidase II protein from human serum is large and structurally complex. It possesses protein-bound lipid and copper components which are essential for the maintenance of its catalytic activity. Treatment of ferroxidase II with 8 M urea, 6 M guanidine hydrochloride, or 6 M guanidine hydrochloride and alkylation does not result in the dissociation of the enzyme into subunits. However, treatment with sodium dodecyl sulfate results in the dissociation of ferroxidase II into two nonidentical subunits, designated S-I and S-II. S-I contains little phospholipid, cholesterol, or copper and has a molecular weight of 3.8-3.9 X 10(5). In contrast, S-II contains bound phospholipid, cholesterol, and copper and has a molecular weight of 2.2-2.4 X 10(5). The lipid compositon of S-II is identical with the native enzyme. Sodium dodecyl sulfate-free S-I exhibits no ferroxidase activity. Immediately following removal of sodium dodecyl sulfate, S-II exhibits ferroxidase activity but S-II rapidly loses its activity in the absence of S-I. The separated subunits spontaneously reassociate upon removal of the sodium dodecyl sulfate to yield a fully active enzyme which chemically appears identical with native ferroxidase II. Furthermore, the reconstituted enzyme is stable. Both native and reconstituted ferroxidase II may be stored at 4 degrees C for 6 weeks without any loss in activity. This suggests that S-II, the copper and lipid-containing subunit, is the catalytic subunit and that S-I is essential for the stabilization of the enzymic activity of S-II. These results provide insight into the molecular structure and chemical composition of ferroxidase II and suggest that the complete native structure of ferroxidase II is required for the maintenance of i-s functional integrity.", "contents": "Dissociation and reconstitution of human ferroxidase II. The ferroxidase II protein from human serum is large and structurally complex. It possesses protein-bound lipid and copper components which are essential for the maintenance of its catalytic activity. Treatment of ferroxidase II with 8 M urea, 6 M guanidine hydrochloride, or 6 M guanidine hydrochloride and alkylation does not result in the dissociation of the enzyme into subunits. However, treatment with sodium dodecyl sulfate results in the dissociation of ferroxidase II into two nonidentical subunits, designated S-I and S-II. S-I contains little phospholipid, cholesterol, or copper and has a molecular weight of 3.8-3.9 X 10(5). In contrast, S-II contains bound phospholipid, cholesterol, and copper and has a molecular weight of 2.2-2.4 X 10(5). The lipid compositon of S-II is identical with the native enzyme. Sodium dodecyl sulfate-free S-I exhibits no ferroxidase activity. Immediately following removal of sodium dodecyl sulfate, S-II exhibits ferroxidase activity but S-II rapidly loses its activity in the absence of S-I. The separated subunits spontaneously reassociate upon removal of the sodium dodecyl sulfate to yield a fully active enzyme which chemically appears identical with native ferroxidase II. Furthermore, the reconstituted enzyme is stable. Both native and reconstituted ferroxidase II may be stored at 4 degrees C for 6 weeks without any loss in activity. This suggests that S-II, the copper and lipid-containing subunit, is the catalytic subunit and that S-I is essential for the stabilization of the enzymic activity of S-II. These results provide insight into the molecular structure and chemical composition of ferroxidase II and suggest that the complete native structure of ferroxidase II is required for the maintenance of i-s functional integrity."}
{"id": "PMID:13824", "title": "Determination of ionization state by resonance Raman spectroscopy Sulfonamide binding to carbonic anhydrase.", "content": "Resonance Raman (RR) spectroscopy has been used to study the ionization state of the sulfonamide, 4'-sulfamylphenyl-2-azo-7-acetamido-1-hydroxynaphthalene-3,-6-disulfonate (Neoprontosil), bound to carbonic anhydrase. The correlation of effects of pH and deuteration on the spectra of model compounds with these effects on the Neoprotosil spectrum allows us to assign spectral bands in the 900-1000 and 100-1200 cm-1 regions to the SO2NH2 group. Large shifts in these bands occur upon ionization of the sulfonamide. On the basis of the positions of bands in the enzyme complex, it was determined that the sulfonamide was bound to the enzyme as SO2NH2, rather than as SO2NH-. Rates of association and dissociation and the dissociation equilibrium constant were measured as a function of pH. The rate behavior for Neoprontosil is consistent with that observed for other sulfonamides and kdissoc/kassoc = kdissoc, suggesting a one-step binding mechanism. Since RR spectroscopy establishes that the final ionization state of the sulfonamide in the enzyme complex is SO2NH2, protonated sulfonamide must bind directly to basic form of the enzyme. These conclusions suggest that sulfonamides form \"outer-space\" complexes with metal at the enzyme active site.", "contents": "Determination of ionization state by resonance Raman spectroscopy Sulfonamide binding to carbonic anhydrase. Resonance Raman (RR) spectroscopy has been used to study the ionization state of the sulfonamide, 4'-sulfamylphenyl-2-azo-7-acetamido-1-hydroxynaphthalene-3,-6-disulfonate (Neoprontosil), bound to carbonic anhydrase. The correlation of effects of pH and deuteration on the spectra of model compounds with these effects on the Neoprotosil spectrum allows us to assign spectral bands in the 900-1000 and 100-1200 cm-1 regions to the SO2NH2 group. Large shifts in these bands occur upon ionization of the sulfonamide. On the basis of the positions of bands in the enzyme complex, it was determined that the sulfonamide was bound to the enzyme as SO2NH2, rather than as SO2NH-. Rates of association and dissociation and the dissociation equilibrium constant were measured as a function of pH. The rate behavior for Neoprontosil is consistent with that observed for other sulfonamides and kdissoc/kassoc = kdissoc, suggesting a one-step binding mechanism. Since RR spectroscopy establishes that the final ionization state of the sulfonamide in the enzyme complex is SO2NH2, protonated sulfonamide must bind directly to basic form of the enzyme. These conclusions suggest that sulfonamides form \"outer-space\" complexes with metal at the enzyme active site."}
{"id": "PMID:13825", "title": "Circular dichroism studies of angiotensin II and analogues: effects of primary sequence, solvent, and pH on the side-chain conformation.", "content": "Conformational aspects of the pressor hormone angiotensin II and 11 of its structural analogues were studied by circular dichroism. Each position of the peptide was singly substituted with an aliphatic residue and alterations of the CD spectra of the resulting analogues in the peptide and aromatic spectral regions (320-250 nm, 250-190 nm) were examined. The spectra of these peptides in 2,2,2-trifluoroethanol solution permit estimation of the relative importance of the various side chains in maintaining the backbone conformation of the hormone. The evolution of the CD spectra in both spectral regions of the peptides in aqueous solution during a titration from pH 1 to pH 12 makes it possible to elucidate further the role of ionizable groups and their interaction with aromatic amino acids such as tyrosine. The results obtained indicate that substitutions in aspartic acid 1, proline 7, and phenylalanine 8 of angiotensin II entail changes in the backbone conformation. On the other hand, the side chains of valine 3, isoleucine 5, and the biologically essential histidine 6 serve mainly to correctly align the phenolic ring of tyrosine in position 4.", "contents": "Circular dichroism studies of angiotensin II and analogues: effects of primary sequence, solvent, and pH on the side-chain conformation. Conformational aspects of the pressor hormone angiotensin II and 11 of its structural analogues were studied by circular dichroism. Each position of the peptide was singly substituted with an aliphatic residue and alterations of the CD spectra of the resulting analogues in the peptide and aromatic spectral regions (320-250 nm, 250-190 nm) were examined. The spectra of these peptides in 2,2,2-trifluoroethanol solution permit estimation of the relative importance of the various side chains in maintaining the backbone conformation of the hormone. The evolution of the CD spectra in both spectral regions of the peptides in aqueous solution during a titration from pH 1 to pH 12 makes it possible to elucidate further the role of ionizable groups and their interaction with aromatic amino acids such as tyrosine. The results obtained indicate that substitutions in aspartic acid 1, proline 7, and phenylalanine 8 of angiotensin II entail changes in the backbone conformation. On the other hand, the side chains of valine 3, isoleucine 5, and the biologically essential histidine 6 serve mainly to correctly align the phenolic ring of tyrosine in position 4."}
{"id": "PMID:13826", "title": "Mechanism of the reaction of hydrated electrons with ferrocytochrome c.", "content": "1. The hydrated electron reacts with ferrocytochrome c to form an unstable intermediate. This intermediate decays in a first-order manner to give, in the first instance, a product which has a similar absorption spectrum in the range 400-610 nm as normal ferricytochrome c. 2. At 21 degrees C the rate constant for the reaction of hydrated electrons with ferrocytochrome c at pH 7.4 (2 mM phosphate buffer) is (3.0 +/- 0.3) = 10(10) M-1 - S-1. As the pH is increased above pH 8.0 the rate constant steadily decreases. The dependence of the rate constant on pH can be explained if ferrocytochrome c has a pK of around 9.2. 3. At 21 degrees C and pH 7.4, the rate constant for the decay of the intermediate is (1.40 +/- 0.15) - 10(5) S-1. This reaction shows no pH dependence in the range 6-2-11.0. 4. A mechanism is proposed whereby the central metal atom of the ferrocytochrome c is oxidased and a thioether bond is reduced. The resulting ferricytochrome c species then slowly develops an absorbance at 606 nm due to the attack of the sulfhydryl group on the haem.", "contents": "Mechanism of the reaction of hydrated electrons with ferrocytochrome c. 1. The hydrated electron reacts with ferrocytochrome c to form an unstable intermediate. This intermediate decays in a first-order manner to give, in the first instance, a product which has a similar absorption spectrum in the range 400-610 nm as normal ferricytochrome c. 2. At 21 degrees C the rate constant for the reaction of hydrated electrons with ferrocytochrome c at pH 7.4 (2 mM phosphate buffer) is (3.0 +/- 0.3) = 10(10) M-1 - S-1. As the pH is increased above pH 8.0 the rate constant steadily decreases. The dependence of the rate constant on pH can be explained if ferrocytochrome c has a pK of around 9.2. 3. At 21 degrees C and pH 7.4, the rate constant for the decay of the intermediate is (1.40 +/- 0.15) - 10(5) S-1. This reaction shows no pH dependence in the range 6-2-11.0. 4. A mechanism is proposed whereby the central metal atom of the ferrocytochrome c is oxidased and a thioether bond is reduced. The resulting ferricytochrome c species then slowly develops an absorbance at 606 nm due to the attack of the sulfhydryl group on the haem."}
{"id": "PMID:13827", "title": "Cation transport in cytochrome oxidase reconstituted vesicles.", "content": "Cation translocation across the membrane of cytochrome oxidase reconstituted vesicles may be followed with a simple spectrophotometric method. Cytochrome oxidase reconstituted vesicles, supplemented with ascorbate and cytochrome c. induce large spectral changes of the positive dye safranine, reversed by uncouplers and inhibitors of respiration. The dye is probably accumulated in the inner space of the vesicles, where it reaches high concentrations and aggregates. The spectral shifts and the absorbance changes, due to aggregation, are proportional to the amount of the dye taken up and depend on the respiratory control. In the presence of potassium, valinomycin causes an inhibition, whereas nigericin stimulates the dye uptake. The data are discussed in terms of electrical potential dependent fluxes.", "contents": "Cation transport in cytochrome oxidase reconstituted vesicles. Cation translocation across the membrane of cytochrome oxidase reconstituted vesicles may be followed with a simple spectrophotometric method. Cytochrome oxidase reconstituted vesicles, supplemented with ascorbate and cytochrome c. induce large spectral changes of the positive dye safranine, reversed by uncouplers and inhibitors of respiration. The dye is probably accumulated in the inner space of the vesicles, where it reaches high concentrations and aggregates. The spectral shifts and the absorbance changes, due to aggregation, are proportional to the amount of the dye taken up and depend on the respiratory control. In the presence of potassium, valinomycin causes an inhibition, whereas nigericin stimulates the dye uptake. The data are discussed in terms of electrical potential dependent fluxes."}
{"id": "PMID:13828", "title": "Energy-linked protonation of quinacrine in beef heart submitochondrial membranes.", "content": "1. The absorption spectrum of quinacrine in aqueous solution, in the visible region, changes with the pH of the medium in the pH range from 6.0 to 9.0 with an isosbestic point at 353 nm. This indicates that the monoprotonated (quinacrine - H+) and the diprotonated (quinacrine - 2H+) forms of quinacrine at equilibrium in this pH range have a 1 to 1 stoichiometry. 2. The monoprotonated and the dipronated forms to quinacrine exhibit similar fluorescence emission spectra, but distinctive fluorescence excitation spectra. 3. The relative fluorescence quantum yields of quinacrine in aqueous media of various pH values are estimated. The relative fluorescence quantum yield of quinacrine at pH 9.0 is more than 3 fold of that at pH 6.0. 4. The fluorescence excitation and emission spectra, as well as the relative fluorescence quantum yield of quinacrine associated with non-energized submitochondrial membranes, are similar to those of quinacrine alone. 5. Analyses of the absorption spectra, the fluorescence excitation spectra and the relative fluorescence quantum yield indicate that the energy-linked fluorescence decrease of quinacrine associated with the energized submitochondrial membranes results from the protonation of quinacrine - H+ to form quinacrine - 2H+. 6. Quantitative data are provided indicating that the maximal efficiency of protonation of quinacrine - H+ to form quinacrine - 2H+ depends on the concentration of H+ in the membranes generated through energy coupling, and the concentration of quinacrine - H+ initially present in the reaction medium. Under optimal conditions virtually complete conversion of quinacrine - H+ into quinacrine - 2H+ is observed. 7. The fluorescence intensity of quinacrine, either alone or associated with non-energized submitochondrial membranes, decreases with increasing temperature. When quinacrine is associated with the energized membranes, however, its fluorescence intensity increases slightly with increasing temperature. This unusual fluorescence behavior towards temperature, together with the fact that under optimal conditions virtually all the quinacrine molecules associated with the energized membranes are in the diprotonated form, further substantiate our earlier conclusion that the diprotonated quinacrine molecules are tightly bound to the energized membranes in a fashion which does not permit ready equilibration with the external medium.", "contents": "Energy-linked protonation of quinacrine in beef heart submitochondrial membranes. 1. The absorption spectrum of quinacrine in aqueous solution, in the visible region, changes with the pH of the medium in the pH range from 6.0 to 9.0 with an isosbestic point at 353 nm. This indicates that the monoprotonated (quinacrine - H+) and the diprotonated (quinacrine - 2H+) forms of quinacrine at equilibrium in this pH range have a 1 to 1 stoichiometry. 2. The monoprotonated and the dipronated forms to quinacrine exhibit similar fluorescence emission spectra, but distinctive fluorescence excitation spectra. 3. The relative fluorescence quantum yields of quinacrine in aqueous media of various pH values are estimated. The relative fluorescence quantum yield of quinacrine at pH 9.0 is more than 3 fold of that at pH 6.0. 4. The fluorescence excitation and emission spectra, as well as the relative fluorescence quantum yield of quinacrine associated with non-energized submitochondrial membranes, are similar to those of quinacrine alone. 5. Analyses of the absorption spectra, the fluorescence excitation spectra and the relative fluorescence quantum yield indicate that the energy-linked fluorescence decrease of quinacrine associated with the energized submitochondrial membranes results from the protonation of quinacrine - H+ to form quinacrine - 2H+. 6. Quantitative data are provided indicating that the maximal efficiency of protonation of quinacrine - H+ to form quinacrine - 2H+ depends on the concentration of H+ in the membranes generated through energy coupling, and the concentration of quinacrine - H+ initially present in the reaction medium. Under optimal conditions virtually complete conversion of quinacrine - H+ into quinacrine - 2H+ is observed. 7. The fluorescence intensity of quinacrine, either alone or associated with non-energized submitochondrial membranes, decreases with increasing temperature. When quinacrine is associated with the energized membranes, however, its fluorescence intensity increases slightly with increasing temperature. This unusual fluorescence behavior towards temperature, together with the fact that under optimal conditions virtually all the quinacrine molecules associated with the energized membranes are in the diprotonated form, further substantiate our earlier conclusion that the diprotonated quinacrine molecules are tightly bound to the energized membranes in a fashion which does not permit ready equilibration with the external medium."}
{"id": "PMID:13829", "title": "Binding of [3H]ctyochalasin B and [3H]colchicine to isolated liver plasma membranes.", "content": "The binding to isolated hepatocyte plasma membranes of radioactively labelled inhibitors of microfilamentous and microtubular protein function ([3H]cytochalasin B and [3H]colchicine, respectively) was studied as one means of assessing the degree of association of these proteins with cell surface membranes. [3H]Cytochalasin B which behaved identically to the unlabelled compound with respect to binding to these membranes was prepared by reduction of cytochalasin A with NaB3H4. The binding was rapid, readily reversible, proportional to the amount of membrane and relatively insensitive to changes of pH or ionic strength. At 10(-6) M [3H]cytochalasin B, glucose of p-chloromercuribenzoate, an inhibitor of glucose transport inhibited binding by about 20%; treatment of membranes with 0.6 M KI which depolymerizes F actin to G actin caused about 60% inhibition of binding. These two types of inhibition were additive indicating two separate classes of binding sites, one associated with sugar transport and one with microfilaments. Filamentous structures with the diameter of microfilaments (50 A) were seen in electron micrographs of thin sections of the membranes. At concentrations greater than 10(-5) M [3H]cytochalasin B, binding was proportional to drug concentration, characteristic of non-specific adsorption or partitioning. Intracellular membranes of the hepatocyte also bound [3H]cytochalasin B, those of the smooth endoplasmic reticulum to a greater extent than plasma membranes. [3H]Colchicine bound to plasma membranes in proportion to the amount of membrane and at a rate compatible with binding to tubulin. However, other properties of the binding including effects of temperature, drug concentration and antisera against tubulin were different from those of binding to tubulin. Hence, no evidence was obtained for association of microtubular elements with these membranes. Despite this there appeared to be an interdependence between microtubule and microfilament inhibitors: vinblastine sulfate stimulated [3H]cytochalasin B binding and cytochalasin B stimulated 3H colchicine binding. [3H]Colchicine also bound to intracellular membranes, especially smooth microsomes.", "contents": "Binding of [3H]ctyochalasin B and [3H]colchicine to isolated liver plasma membranes. The binding to isolated hepatocyte plasma membranes of radioactively labelled inhibitors of microfilamentous and microtubular protein function ([3H]cytochalasin B and [3H]colchicine, respectively) was studied as one means of assessing the degree of association of these proteins with cell surface membranes. [3H]Cytochalasin B which behaved identically to the unlabelled compound with respect to binding to these membranes was prepared by reduction of cytochalasin A with NaB3H4. The binding was rapid, readily reversible, proportional to the amount of membrane and relatively insensitive to changes of pH or ionic strength. At 10(-6) M [3H]cytochalasin B, glucose of p-chloromercuribenzoate, an inhibitor of glucose transport inhibited binding by about 20%; treatment of membranes with 0.6 M KI which depolymerizes F actin to G actin caused about 60% inhibition of binding. These two types of inhibition were additive indicating two separate classes of binding sites, one associated with sugar transport and one with microfilaments. Filamentous structures with the diameter of microfilaments (50 A) were seen in electron micrographs of thin sections of the membranes. At concentrations greater than 10(-5) M [3H]cytochalasin B, binding was proportional to drug concentration, characteristic of non-specific adsorption or partitioning. Intracellular membranes of the hepatocyte also bound [3H]cytochalasin B, those of the smooth endoplasmic reticulum to a greater extent than plasma membranes. [3H]Colchicine bound to plasma membranes in proportion to the amount of membrane and at a rate compatible with binding to tubulin. However, other properties of the binding including effects of temperature, drug concentration and antisera against tubulin were different from those of binding to tubulin. Hence, no evidence was obtained for association of microtubular elements with these membranes. Despite this there appeared to be an interdependence between microtubule and microfilament inhibitors: vinblastine sulfate stimulated [3H]cytochalasin B binding and cytochalasin B stimulated 3H colchicine binding. [3H]Colchicine also bound to intracellular membranes, especially smooth microsomes."}
{"id": "PMID:13830", "title": "Membrane-bound ATPase of intact vacuoles and tonoplasts isolated from mature plant tissue.", "content": "Intact vacuoles were isolated from petals of Hippeastrum and Tulipa (Wagner G.J. and Siegelman, H.W. (1975) Science 190, 1298--1299). The ATPase activity of fresh vacuole suspensions was found to be 2--3 times that of protoplasts from the same tissue. 70--80% of the ATPase activity of intact vacuoles was recovered in tonoplast preparations. The antibiotic Dio-9 at 6mug/10(6) vacuoles or protoplasts causes 40% inhibition. However, only the protoplast ATPase is sensitive to oligomycin. N,N'-dicyclohexylcarbodiimide (DCCD) slightly stimulates ATPase activity in both vacuole and protoplast suspensions, whereas ethyl-3-(3-dimethylaminopropyl carbodiimide) (EDAC) strongly inhibits. Spectrophotometric studies show that in the petal the vacuolar contents have a pH of 4.0 for Tuplipa and 4.3 for Hippeastrum, whereas the intact isolated vacuole has an internal pH of 7.0 (in pH 8.0 buffer) for (Tulipa and about 7.3 for Hippeastrum. Internal ion concentrations of 150, 46, 30, 30 and 6 mM were found for K+, Na+, Mg2+, Cl-, and Ca2+ respectively, which are about the same as those in protoplasts.", "contents": "Membrane-bound ATPase of intact vacuoles and tonoplasts isolated from mature plant tissue. Intact vacuoles were isolated from petals of Hippeastrum and Tulipa (Wagner G.J. and Siegelman, H.W. (1975) Science 190, 1298--1299). The ATPase activity of fresh vacuole suspensions was found to be 2--3 times that of protoplasts from the same tissue. 70--80% of the ATPase activity of intact vacuoles was recovered in tonoplast preparations. The antibiotic Dio-9 at 6mug/10(6) vacuoles or protoplasts causes 40% inhibition. However, only the protoplast ATPase is sensitive to oligomycin. N,N'-dicyclohexylcarbodiimide (DCCD) slightly stimulates ATPase activity in both vacuole and protoplast suspensions, whereas ethyl-3-(3-dimethylaminopropyl carbodiimide) (EDAC) strongly inhibits. Spectrophotometric studies show that in the petal the vacuolar contents have a pH of 4.0 for Tuplipa and 4.3 for Hippeastrum, whereas the intact isolated vacuole has an internal pH of 7.0 (in pH 8.0 buffer) for (Tulipa and about 7.3 for Hippeastrum. Internal ion concentrations of 150, 46, 30, 30 and 6 mM were found for K+, Na+, Mg2+, Cl-, and Ca2+ respectively, which are about the same as those in protoplasts."}
{"id": "PMID:13831", "title": "Ureidosuccinic acid permeation in Saccharomyces cerevisiae.", "content": "Some strains of Saccharomyces cerevisiae exhibit a specific transport system for ureidosuccinic acid, which is regulated by nitrogen metabolism. Ureidosuccinic acid uptake occurs with proline but with ammonium sulfate as nitrogen source it is inhibited. The V for transport is 20-25 mumol/ml cell water per min. The apparent Km is 3-10(-5) M. For the urep1 mutant (ureidosuccinic acid permease less) the internal concentration never exceeds the external one. In the permease plus strain ureidosuccinic acid can be concentrated up to 10 000 fold and the accumulated compound remains unchanged in the cells. Energy poisons such as dinitrophenol, carbonyl cyanide-m-chlorophenyldrazone (CCCP) or NaN3 inhibit the uptake. No significant efflux of the accumulated compound occurs even in the presence of these drugs. The specificity of the permease is very strict, only amino acids carrying an alpha-N-carbamyl group are strongly competitive inhibitors. The high concentration capacity of the cells and lack of active exit of the accumulated compound support the hypothesis of a carrier mediated active transport system.", "contents": "Ureidosuccinic acid permeation in Saccharomyces cerevisiae. Some strains of Saccharomyces cerevisiae exhibit a specific transport system for ureidosuccinic acid, which is regulated by nitrogen metabolism. Ureidosuccinic acid uptake occurs with proline but with ammonium sulfate as nitrogen source it is inhibited. The V for transport is 20-25 mumol/ml cell water per min. The apparent Km is 3-10(-5) M. For the urep1 mutant (ureidosuccinic acid permease less) the internal concentration never exceeds the external one. In the permease plus strain ureidosuccinic acid can be concentrated up to 10 000 fold and the accumulated compound remains unchanged in the cells. Energy poisons such as dinitrophenol, carbonyl cyanide-m-chlorophenyldrazone (CCCP) or NaN3 inhibit the uptake. No significant efflux of the accumulated compound occurs even in the presence of these drugs. The specificity of the permease is very strict, only amino acids carrying an alpha-N-carbamyl group are strongly competitive inhibitors. The high concentration capacity of the cells and lack of active exit of the accumulated compound support the hypothesis of a carrier mediated active transport system."}
{"id": "PMID:13832", "title": "The reactivities of tyrosine and tryptophan residues in lipid-bound cytochrome b5.", "content": "Purified cytochrome b5 from rabbit liver microsomes was bound to liposomes prepared from microsomal lipids. Tyrosyl and tryptophyl side chains of the protein were modified by water-soluble reagents and the reactivities of these amino acid residues in the liposome-bound cytochrome b5 were compared to those of the free protein. At pH 13, 80% of the tyrosines in lipid-free cytochrome b5 ionized immediately, whereas in the lipid-bound protein only 65% ionized within the first minute. In contrast, acetylation with acetylimidazole resulted in the conversion of all 5 tyrosine groups of lipid-free as well as lipid-bound cytochrome b5 into O-acetylated derivatives, which upon treatment with hydroxylamine were completely deacetylated. Reaction with N-bromosuccinimide revealed that only 60% of the 4 tryptophan residues present in cytochrome b5 were accessible to the reagent in the lipid-bound protein, although all tryptophans could be modified in lipid free cytochrome b5. It was concluded that the two tyrosines in the region linking the protein to the membrane are not shielded by lipid bilayer but that of the three tryptophans in the same region one is completely buried in the membrane, whereas the remaining two tryptophans may be both partly exposed to the solvent or alternatively, one may be partially and the other completely exposed.", "contents": "The reactivities of tyrosine and tryptophan residues in lipid-bound cytochrome b5. Purified cytochrome b5 from rabbit liver microsomes was bound to liposomes prepared from microsomal lipids. Tyrosyl and tryptophyl side chains of the protein were modified by water-soluble reagents and the reactivities of these amino acid residues in the liposome-bound cytochrome b5 were compared to those of the free protein. At pH 13, 80% of the tyrosines in lipid-free cytochrome b5 ionized immediately, whereas in the lipid-bound protein only 65% ionized within the first minute. In contrast, acetylation with acetylimidazole resulted in the conversion of all 5 tyrosine groups of lipid-free as well as lipid-bound cytochrome b5 into O-acetylated derivatives, which upon treatment with hydroxylamine were completely deacetylated. Reaction with N-bromosuccinimide revealed that only 60% of the 4 tryptophan residues present in cytochrome b5 were accessible to the reagent in the lipid-bound protein, although all tryptophans could be modified in lipid free cytochrome b5. It was concluded that the two tyrosines in the region linking the protein to the membrane are not shielded by lipid bilayer but that of the three tryptophans in the same region one is completely buried in the membrane, whereas the remaining two tryptophans may be both partly exposed to the solvent or alternatively, one may be partially and the other completely exposed."}
{"id": "PMID:13833", "title": "Calcium ion-flux across phosphatidylcholine membranes mediated by ionophore A23187.", "content": "The antibiotic A23187 carries Ca2+ across M\u00fcller-Rudin membranes made from 1,2-dierucoyl-sn-glycero-3-phosphocholine and n-decane. The conductance of the membranes is not increased by the Ca2+-transport. The flux depends linearly on Ca2+ concentration and ionophore concentration (above pH 6). It increases with increasing pH, approximately by a factor of 4-5 between pH 6 and pH 8. Maximal Ca2+-fluxes of about 10(-10) mol-cm-2-s-1 were found. A counter transport of H+ could not be detected. The complex formation between A23187 and Ca2+ in egg phosphotidylcholine vesicles was studied spectroscopically. The results are consistent with the formation of a 2:1 complex. Optical absorption measurements on single phophatidylcholine membranes were used to calculate the concentration of membrane-bound ionophore A23187.", "contents": "Calcium ion-flux across phosphatidylcholine membranes mediated by ionophore A23187. The antibiotic A23187 carries Ca2+ across M\u00fcller-Rudin membranes made from 1,2-dierucoyl-sn-glycero-3-phosphocholine and n-decane. The conductance of the membranes is not increased by the Ca2+-transport. The flux depends linearly on Ca2+ concentration and ionophore concentration (above pH 6). It increases with increasing pH, approximately by a factor of 4-5 between pH 6 and pH 8. Maximal Ca2+-fluxes of about 10(-10) mol-cm-2-s-1 were found. A counter transport of H+ could not be detected. The complex formation between A23187 and Ca2+ in egg phosphotidylcholine vesicles was studied spectroscopically. The results are consistent with the formation of a 2:1 complex. Optical absorption measurements on single phophatidylcholine membranes were used to calculate the concentration of membrane-bound ionophore A23187."}
{"id": "PMID:13834", "title": "Permeability characteristics of erythrocyte ghosts prepared under isoionic conditions by a glycol-induced osmotic lysis.", "content": "A detailed study has been made of the permeability characteristics of human erythrocyte ghosts prepared under isoionic conditions by a glycol-induced lysis (Billah, M.M., Finean, J.B., Coleman, R. and Michell, R.H. (1976) Biochim. Biophys. Acta 433, 45-54). Impermeability to large molecules such as dextran (average molecular weight 70 000) was restored immediately and spontaneously after each of the 5-7 lyses that were required to remove all of the haemoglobin. Permeabilities to smaller molecules such as MgATP2-, [3H]inositol and [14C]choline were initially high but could be greatly reduced by incubation at 37 degrees C for an hour. The extent of such resealing decreased as the number of lyses to which the ghosts had been subjected increased. Both removal of haemoglobin and permeabilities to small molecules were affected significantly by pH, CA3+ concentrations and divalent cation chelators. Maximum resealing was achieved in ghosts prepared in the basic ionic medium (130 mM KCl, 10 nM NaCl, 2 mM MgCl2, 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES)) at pH 7.0 (0 degrees C) and with a calcium level around 10(-5) M. Acidic pH facilitated the removal of haemoglobin whilst the presence of divalent cation chelators showed down its release. Retention of K+ by ghosts leaded with K+ during the first lysis and subsequently incubated at 37 degrees C was substantial but lation chelators slowed down its released. Retention of K+ by ghosts loaded with K+ during the first lysis and subsequently incubated at 37 degrees C was substantial but little K+ could be retained within the haemoglobin-free ghosts. Permeability of the ghosts to K+ after one lysis was affected by temperature, pH, Ca2+ concentrations and by the presence of divalent cation chelators.", "contents": "Permeability characteristics of erythrocyte ghosts prepared under isoionic conditions by a glycol-induced osmotic lysis. A detailed study has been made of the permeability characteristics of human erythrocyte ghosts prepared under isoionic conditions by a glycol-induced lysis (Billah, M.M., Finean, J.B., Coleman, R. and Michell, R.H. (1976) Biochim. Biophys. Acta 433, 45-54). Impermeability to large molecules such as dextran (average molecular weight 70 000) was restored immediately and spontaneously after each of the 5-7 lyses that were required to remove all of the haemoglobin. Permeabilities to smaller molecules such as MgATP2-, [3H]inositol and [14C]choline were initially high but could be greatly reduced by incubation at 37 degrees C for an hour. The extent of such resealing decreased as the number of lyses to which the ghosts had been subjected increased. Both removal of haemoglobin and permeabilities to small molecules were affected significantly by pH, CA3+ concentrations and divalent cation chelators. Maximum resealing was achieved in ghosts prepared in the basic ionic medium (130 mM KCl, 10 nM NaCl, 2 mM MgCl2, 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES)) at pH 7.0 (0 degrees C) and with a calcium level around 10(-5) M. Acidic pH facilitated the removal of haemoglobin whilst the presence of divalent cation chelators showed down its release. Retention of K+ by ghosts leaded with K+ during the first lysis and subsequently incubated at 37 degrees C was substantial but lation chelators slowed down its released. Retention of K+ by ghosts loaded with K+ during the first lysis and subsequently incubated at 37 degrees C was substantial but little K+ could be retained within the haemoglobin-free ghosts. Permeability of the ghosts to K+ after one lysis was affected by temperature, pH, Ca2+ concentrations and by the presence of divalent cation chelators."}
{"id": "PMID:13835", "title": "Studies on membrane fusion. III. The role of calcium-induced phase changes.", "content": "The interaction of phosphatidylserine vesicles with Ca2+ and Mg2+ has been examined by several techniques to study the mechanism of membrane fusion. Data are presented on the effects of Ca2+ and Mg2+ on vesicle permeability, thermotropic phase transitions and morphology determined by differential scanning calorimetry, X-ray diffraction, and freeze-fracture electron microscopy. These data are discussed in relation to information concerning Ca2+ binding, charge neutralization, molecular packing, vesicle aggregation, phase transitions, phase separations and vesicle fusion. The results indicate that at Ca2+ concentrations of 1.0-2.0 mM, a highly cooperative phenomenon occurs which results in increased vesicle permeability, aggregation and fusion of the vesicles. Under these conditions the hydrocarbon chains of the lipid bilayers undergo a phase change from a fluid to a crystalline state. The aggregation of vesicles that is observed during fusion is not sufficient range of 2.0-5.0 mM induces aggregation of phosphatidylserine vesicles but no significant fusion nor a phase change. From the effect of variations in pH, temperature, Ca2+ and Mg2+ concentration on the fusion of vesicles, it is concluded that the key event leading to vesicle membrane fusion is the isothermic phase change induced by the bivalent metals. It is proposed that this phase change induces a transient destabilization of the bilayer membranes that become susceptible to fusion at domain boundaries.", "contents": "Studies on membrane fusion. III. The role of calcium-induced phase changes. The interaction of phosphatidylserine vesicles with Ca2+ and Mg2+ has been examined by several techniques to study the mechanism of membrane fusion. Data are presented on the effects of Ca2+ and Mg2+ on vesicle permeability, thermotropic phase transitions and morphology determined by differential scanning calorimetry, X-ray diffraction, and freeze-fracture electron microscopy. These data are discussed in relation to information concerning Ca2+ binding, charge neutralization, molecular packing, vesicle aggregation, phase transitions, phase separations and vesicle fusion. The results indicate that at Ca2+ concentrations of 1.0-2.0 mM, a highly cooperative phenomenon occurs which results in increased vesicle permeability, aggregation and fusion of the vesicles. Under these conditions the hydrocarbon chains of the lipid bilayers undergo a phase change from a fluid to a crystalline state. The aggregation of vesicles that is observed during fusion is not sufficient range of 2.0-5.0 mM induces aggregation of phosphatidylserine vesicles but no significant fusion nor a phase change. From the effect of variations in pH, temperature, Ca2+ and Mg2+ concentration on the fusion of vesicles, it is concluded that the key event leading to vesicle membrane fusion is the isothermic phase change induced by the bivalent metals. It is proposed that this phase change induces a transient destabilization of the bilayer membranes that become susceptible to fusion at domain boundaries."}
{"id": "PMID:13836", "title": "Bis-(4-methylumbelliferyl) phosphate as a substrate for the surface membrane-associated phosphodiesterase activity of pig platelets.", "content": "It was found that the newly-available compound, bis-(4-methylumbelliferyl) phosphate, could be used as a substrate for the pig platelet surface membrane-associated phosphodiesterase activity, usually assayed with bis-(p-nitrophenyl) phosphate. This enzyme activity is distinct from the phosphodiesterase activity towards 5'-dTMP-P-nitrophenyl ester, which is probably associated with intracellular membrane structures in platelets. Consequently, the use of the 4-methylumbelliferyl derivative as substrate for the phosphodiesterase activity provides a sensitive, fluorimetric assay for this marker enzyme of the platelet surface membrane.", "contents": "Bis-(4-methylumbelliferyl) phosphate as a substrate for the surface membrane-associated phosphodiesterase activity of pig platelets. It was found that the newly-available compound, bis-(4-methylumbelliferyl) phosphate, could be used as a substrate for the pig platelet surface membrane-associated phosphodiesterase activity, usually assayed with bis-(p-nitrophenyl) phosphate. This enzyme activity is distinct from the phosphodiesterase activity towards 5'-dTMP-P-nitrophenyl ester, which is probably associated with intracellular membrane structures in platelets. Consequently, the use of the 4-methylumbelliferyl derivative as substrate for the phosphodiesterase activity provides a sensitive, fluorimetric assay for this marker enzyme of the platelet surface membrane."}
{"id": "PMID:13837", "title": "A specific polyadenylase from Escherichia coli K12.", "content": "A polyadenylase, degrading specifically poly(A) sequences was isolated from Escherichia coli K12. The enzyme was purified about 850 times to practically electrophoretic homogeneity. It was free of poly(A) polymerase activity, as well as of the well known E. coli RNAases I and II. It is stimulated by bivalent cations like Mg2+ and Mn2+ and splits poly(A) to 3'-AMP and therefore it can be considered as an exonuclease. The enzyme does not degrade any other ribohomopolymer or RNA.", "contents": "A specific polyadenylase from Escherichia coli K12. A polyadenylase, degrading specifically poly(A) sequences was isolated from Escherichia coli K12. The enzyme was purified about 850 times to practically electrophoretic homogeneity. It was free of poly(A) polymerase activity, as well as of the well known E. coli RNAases I and II. It is stimulated by bivalent cations like Mg2+ and Mn2+ and splits poly(A) to 3'-AMP and therefore it can be considered as an exonuclease. The enzyme does not degrade any other ribohomopolymer or RNA."}
{"id": "PMID:13838", "title": "Kinetic formulations for the oxidation and the reduction of glyoxylate by lactate dehydrogenase.", "content": "Chicken liver lactate dehydrogenase (L-lactate : NAD+ oxidoreductase, EC 1.1.1.27) irreversibly catalyses the oxidation of glyoxylate (hydrated form) (I) to oxalate (pH = 9.6) and the reduction of (non-hydrated form) (II) to glycolate (pH = 7.4). (I) attaches to the enzyme in the pyruvate binding site and (II) attaches to the enzyme at the L-lactate binding site. The oxidation of (I) (pH = 9.6) is adapted to the following mechanism: (see book). The abortive complexes, E-NADH-I and E-NAD+-II, are responsible for the inhibition by excess substrate in the reduction and oxidation systems, respectively. When lactate dehydrogenase and NAD+ are preincubated, E-NAD+- NAD+ appears and causes inhibition by excess NAD+ in the glyoxylate-lactate dehydrogenase-NAD+ and L-lactate-lactate dehydrogenase-NAD+ systems; the second NAD+ molecule attaches to the enzyme at the L-lactate binding site.", "contents": "Kinetic formulations for the oxidation and the reduction of glyoxylate by lactate dehydrogenase. Chicken liver lactate dehydrogenase (L-lactate : NAD+ oxidoreductase, EC 1.1.1.27) irreversibly catalyses the oxidation of glyoxylate (hydrated form) (I) to oxalate (pH = 9.6) and the reduction of (non-hydrated form) (II) to glycolate (pH = 7.4). (I) attaches to the enzyme in the pyruvate binding site and (II) attaches to the enzyme at the L-lactate binding site. The oxidation of (I) (pH = 9.6) is adapted to the following mechanism: (see book). The abortive complexes, E-NADH-I and E-NAD+-II, are responsible for the inhibition by excess substrate in the reduction and oxidation systems, respectively. When lactate dehydrogenase and NAD+ are preincubated, E-NAD+- NAD+ appears and causes inhibition by excess NAD+ in the glyoxylate-lactate dehydrogenase-NAD+ and L-lactate-lactate dehydrogenase-NAD+ systems; the second NAD+ molecule attaches to the enzyme at the L-lactate binding site."}
{"id": "PMID:13839", "title": "Purification and properties of aldehyde dehydrogenase from Proteus vulgaris.", "content": "NADP-linked aldehyde dehydrogenase (aldehyde : NADP+ oxidoreductase, EC 1.2.1.4) was purified from Proteus vulgaris to the stage of homogeneity as judged by ultracentrifugation and polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme was estimated to be 130000 by gel filtration. The enzyme which was crystallized from ammonium sulfate solution, lost its activity. The enzyme did not require coenzyme A, and the reaction was completely dependent on ammonium ions which could be partially replaced by Rb+ or K+. The optimum pH was about 9. Broad substrate specificity was observed and Km values for propionaldehyde, acetaldehyde and isovaleraldehyde were 1.7 - 10(-5), 4 - 10(-5) and 3 - 10(-5) M, respectively. The physiological role of the enzyme in living cells is obscure, but might account for another degradative pathway of L-leucine in P. vulgaris differing from the established pathway.", "contents": "Purification and properties of aldehyde dehydrogenase from Proteus vulgaris. NADP-linked aldehyde dehydrogenase (aldehyde : NADP+ oxidoreductase, EC 1.2.1.4) was purified from Proteus vulgaris to the stage of homogeneity as judged by ultracentrifugation and polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme was estimated to be 130000 by gel filtration. The enzyme which was crystallized from ammonium sulfate solution, lost its activity. The enzyme did not require coenzyme A, and the reaction was completely dependent on ammonium ions which could be partially replaced by Rb+ or K+. The optimum pH was about 9. Broad substrate specificity was observed and Km values for propionaldehyde, acetaldehyde and isovaleraldehyde were 1.7 - 10(-5), 4 - 10(-5) and 3 - 10(-5) M, respectively. The physiological role of the enzyme in living cells is obscure, but might account for another degradative pathway of L-leucine in P. vulgaris differing from the established pathway."}
{"id": "PMID:13840", "title": "Glucokinase of pea seeds.", "content": "1. Glucokinase (ATP : D-glucose 6-phosphotransferase, EC 2.7.1.2) was extracted from pea seeds and purified by fractionation with (NH4)2SO4 and chromatography on DEAE-cellulose and Sephadex. 2. The relative rates of phosphorylation of glucose, mannose and fructose (final concentration 5 mM) were 100, 64 and 11. 3. The Km for glucose of pea-seed glucokinase was 70 muM and the Km for mannose was 0.5 mM. The Km for fructose was much higher (30 mM). 4. Mg2+ ions were essential for activity. Mn2+ could partially replace Mg2+. 5. Enzyme activity was not inhibited by glucose 6-phosphate. A number of other metabolites had no effect on glucokinase activity. 6. Pea-seed glucokinase was inhibited by relatively low concentrations of ADP.", "contents": "Glucokinase of pea seeds. 1. Glucokinase (ATP : D-glucose 6-phosphotransferase, EC 2.7.1.2) was extracted from pea seeds and purified by fractionation with (NH4)2SO4 and chromatography on DEAE-cellulose and Sephadex. 2. The relative rates of phosphorylation of glucose, mannose and fructose (final concentration 5 mM) were 100, 64 and 11. 3. The Km for glucose of pea-seed glucokinase was 70 muM and the Km for mannose was 0.5 mM. The Km for fructose was much higher (30 mM). 4. Mg2+ ions were essential for activity. Mn2+ could partially replace Mg2+. 5. Enzyme activity was not inhibited by glucose 6-phosphate. A number of other metabolites had no effect on glucokinase activity. 6. Pea-seed glucokinase was inhibited by relatively low concentrations of ADP."}
{"id": "PMID:13841", "title": "Purification and properties of polyphosphoinositide phosphomonoesterase from rat brain.", "content": "1. On subcellular fractionation of rat brain homogenate, polyphosphoinositide phosphomonoesterase activity was greater in the cytosol than the membranous fractions. 2. The enzyme was purified from the cytosol by column chromatography on DEAE-cellulose, calcium phosphate gel and Sephadex G-100. 3. The final preparation of the enzyme showed a 430-fold purification over the whole homogenate and appeared to be homogeneous since it gave a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis and on isoelectric focusing. The enzyme has a relatively low molecular weight and an isoelectric point of 6.8. 4. The phosphatase showed a high affinity for triphosphoinositide. Without added Mg2+, the Km was 25 muM and V was 33 mumol Pi released/min/mg protein. 5. The enzyme hydrolysed diphosphoinositide at a slower rate than triphosphoinositide. In the presence of 10 mM Mg2+, the Km values for triphosphoinositide and diphosphoinositide were 5 muM and 25 muM respectively and V was the same for each substrate. 6. Both Mg2+ and Ca2+ activated the enzyme. While Ca2+ produced maximum activation at 100 muM, a much higher concentration of Mg2+ (10 mM) was required to elicit comparable activation. The enzyme did not show an absolute requirement for Mg2+ or Ca2+ as it exhibited low activity in the presence of 0.5 mM EDTA or EGTA. 7. The phosphatase showed maximum activity between 7.4 and 7.6. A drop in pH to 7.0 activated it almost completely, whereas an increase in pH to 8.0 halved the activity. 7.0 activated it almost completely, whereas an increase in pH to 8.0 halved the activity.", "contents": "Purification and properties of polyphosphoinositide phosphomonoesterase from rat brain. 1. On subcellular fractionation of rat brain homogenate, polyphosphoinositide phosphomonoesterase activity was greater in the cytosol than the membranous fractions. 2. The enzyme was purified from the cytosol by column chromatography on DEAE-cellulose, calcium phosphate gel and Sephadex G-100. 3. The final preparation of the enzyme showed a 430-fold purification over the whole homogenate and appeared to be homogeneous since it gave a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis and on isoelectric focusing. The enzyme has a relatively low molecular weight and an isoelectric point of 6.8. 4. The phosphatase showed a high affinity for triphosphoinositide. Without added Mg2+, the Km was 25 muM and V was 33 mumol Pi released/min/mg protein. 5. The enzyme hydrolysed diphosphoinositide at a slower rate than triphosphoinositide. In the presence of 10 mM Mg2+, the Km values for triphosphoinositide and diphosphoinositide were 5 muM and 25 muM respectively and V was the same for each substrate. 6. Both Mg2+ and Ca2+ activated the enzyme. While Ca2+ produced maximum activation at 100 muM, a much higher concentration of Mg2+ (10 mM) was required to elicit comparable activation. The enzyme did not show an absolute requirement for Mg2+ or Ca2+ as it exhibited low activity in the presence of 0.5 mM EDTA or EGTA. 7. The phosphatase showed maximum activity between 7.4 and 7.6. A drop in pH to 7.0 activated it almost completely, whereas an increase in pH to 8.0 halved the activity. 7.0 activated it almost completely, whereas an increase in pH to 8.0 halved the activity."}
{"id": "PMID:13842", "title": "Calf thymus alkaline phosphatase. I. Properties of the membrane-bound enzyme.", "content": "A membrane fraction from calf thymocytes was used to investigate molecular and catalytic properties of membrane-bound alkaline phosphatase (ortho-phosphoric-monoester phosphohydrolase EC 3.1.3.1). The principal findings were: 1. Solubilization of membranes with the non-ionic detergent Triton X-100 increases alkaline phosphatase activity by 30-40%. The enzyme activity elutes in a single peak (Stokes' radius = 7.7 nm) after chromatography in Sepharose 6B in the presence of Triton X-100. The activity also sediments as a single component of approx. 6.4 S during centrifugation in sucrose gradients containing Triton X-100. 2. Ion-exchange chromatography and isoelectric focusing in the presence of Triton X-100 indicate substantial charge heterogeneity. Two overlapping bands, a peak at pH 5.92 with a pronounced shoulder at pH 5.29, are apparent by isoelectric focusing. 3. The pH optimum for hydrolysis of p-nitrophenylphosphate (pNPhP) by the undissolved enzyme(s) is 9.57. Half-maximal activity occurs at pH 8.65 and ph 10.45. Triton X-100 has no effect on the pH profile. 4. Catalytic activity is affected by amines, especially analogues of ethanolamine. Diethanolamine exerts a unique stimulatory effect, but does not change the pH dependency. Increasing the concentration of diethanolamine from 0 to 1 M causes a 6-fold increase in Km and a 10-fold increase in the rate of hydrolysis of pNPhP. Glycine is inhibitory. 5. EDTA causes an irreversible loss of activity with t1/2 (1 mM EDTA, pH 8.2, 23 degrees C) = 3.5 h. Optimal activity is achieved in 0.1--1.0 mM Mg2+, although this does not cause the degree of activation reported to occur with the purified enzymes. Other divalent ions are inhibitory. Concentrations required to reduce activity to 50% of control are: Zn2+, 4.0 muM (no added Mg2+) and 30 muM (in the presence of 1 mM Mg2+); Mn2+, 0.25 mM (+/- Mg2+); Ca2+, 20 mM (+/- Mg2+). 6. Monovalent cations have little effect on activity. In the absence of added Mg2+, 50--150 mM Na+ is partially inhibitory, but markedly less so in the presence of 1 mM Mg2+. K+ has no significant effect. 7. Of the substrates tested, pNPhP (Km = 44 muM) was most rapidly hydrolyzed. Other substrates (rate relative to pNPhP) were alpha-naphthylphosphate (0.79), 2'-AMP (0.80), 5'-AMP (0.70), 3'-AMP (0.63), alpha-glycerophosphate (0.47) and glucose 6-phosphate (0.35). Phosphodiesterase activity was less than or equal to 10% of the phosphomonoesterase activity (for pNPhP) as evidenced by the lack of hydrolysis of bis(p-nitrophenyl)-phosphate and cyclic 3',5'-AMP. The ability of these substances to inhibit hydrolysis of pNPhP reflected their capacity as substrates, i.e. the most inhibitory were the most rapidly hydrolyzed.", "contents": "Calf thymus alkaline phosphatase. I. Properties of the membrane-bound enzyme. A membrane fraction from calf thymocytes was used to investigate molecular and catalytic properties of membrane-bound alkaline phosphatase (ortho-phosphoric-monoester phosphohydrolase EC 3.1.3.1). The principal findings were: 1. Solubilization of membranes with the non-ionic detergent Triton X-100 increases alkaline phosphatase activity by 30-40%. The enzyme activity elutes in a single peak (Stokes' radius = 7.7 nm) after chromatography in Sepharose 6B in the presence of Triton X-100. The activity also sediments as a single component of approx. 6.4 S during centrifugation in sucrose gradients containing Triton X-100. 2. Ion-exchange chromatography and isoelectric focusing in the presence of Triton X-100 indicate substantial charge heterogeneity. Two overlapping bands, a peak at pH 5.92 with a pronounced shoulder at pH 5.29, are apparent by isoelectric focusing. 3. The pH optimum for hydrolysis of p-nitrophenylphosphate (pNPhP) by the undissolved enzyme(s) is 9.57. Half-maximal activity occurs at pH 8.65 and ph 10.45. Triton X-100 has no effect on the pH profile. 4. Catalytic activity is affected by amines, especially analogues of ethanolamine. Diethanolamine exerts a unique stimulatory effect, but does not change the pH dependency. Increasing the concentration of diethanolamine from 0 to 1 M causes a 6-fold increase in Km and a 10-fold increase in the rate of hydrolysis of pNPhP. Glycine is inhibitory. 5. EDTA causes an irreversible loss of activity with t1/2 (1 mM EDTA, pH 8.2, 23 degrees C) = 3.5 h. Optimal activity is achieved in 0.1--1.0 mM Mg2+, although this does not cause the degree of activation reported to occur with the purified enzymes. Other divalent ions are inhibitory. Concentrations required to reduce activity to 50% of control are: Zn2+, 4.0 muM (no added Mg2+) and 30 muM (in the presence of 1 mM Mg2+); Mn2+, 0.25 mM (+/- Mg2+); Ca2+, 20 mM (+/- Mg2+). 6. Monovalent cations have little effect on activity. In the absence of added Mg2+, 50--150 mM Na+ is partially inhibitory, but markedly less so in the presence of 1 mM Mg2+. K+ has no significant effect. 7. Of the substrates tested, pNPhP (Km = 44 muM) was most rapidly hydrolyzed. Other substrates (rate relative to pNPhP) were alpha-naphthylphosphate (0.79), 2'-AMP (0.80), 5'-AMP (0.70), 3'-AMP (0.63), alpha-glycerophosphate (0.47) and glucose 6-phosphate (0.35). Phosphodiesterase activity was less than or equal to 10% of the phosphomonoesterase activity (for pNPhP) as evidenced by the lack of hydrolysis of bis(p-nitrophenyl)-phosphate and cyclic 3',5'-AMP. The ability of these substances to inhibit hydrolysis of pNPhP reflected their capacity as substrates, i.e. the most inhibitory were the most rapidly hydrolyzed."}
{"id": "PMID:13843", "title": "Purification and properties of one component of acid phosphatase produced by Aspergillus niger.", "content": "One component, the i form, of acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) produced by Aspergillus niger was purified from the mycelial extract. The purified enzyme was homogenous on Sephadex G-200 gel filtration, disc electrophoresis and heat inactivation. The purified enzyme was studied and the following results were obtained: 1. The enzyme catalyzed the hydrolysis of a wide variety of phosphomonoesters, but not that of bis(p-nitrophenyl)phosphate, adenosine 3',5'-cyclic monophosphate, fructose 1,6-diphosphate, adenosine 5'-diphosphate or adenosine 5'-triphosphate. 2. Fluoride, orthophosphate, arsenate, borate, molybdate and (+)-tartrate acted as inhibitors. This enzyme was inactivated by N-bromosuccinimide and 2-hydroxy-5-nitrobenzyl bromide, and was not affected by p-chloromercuribenzoate, N-acetylimidazole, p-diazobenzenesulfonic acid and tetranitromethane. From these results, tryptophan was estimated to play an important role in the enzyme activity. 3. The apparent molecular weight was 310000 by Sephadex G-200 gel filtration. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate suggested that the molecular weight of the subunit was approximately 89000. 4. The purified enzyme contained 29% carbohydrate consisting of glucosamine, mannose and galactose. The amino acid composition of this enzyme was not specific compared with other known acid phosphatases.", "contents": "Purification and properties of one component of acid phosphatase produced by Aspergillus niger. One component, the i form, of acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) produced by Aspergillus niger was purified from the mycelial extract. The purified enzyme was homogenous on Sephadex G-200 gel filtration, disc electrophoresis and heat inactivation. The purified enzyme was studied and the following results were obtained: 1. The enzyme catalyzed the hydrolysis of a wide variety of phosphomonoesters, but not that of bis(p-nitrophenyl)phosphate, adenosine 3',5'-cyclic monophosphate, fructose 1,6-diphosphate, adenosine 5'-diphosphate or adenosine 5'-triphosphate. 2. Fluoride, orthophosphate, arsenate, borate, molybdate and (+)-tartrate acted as inhibitors. This enzyme was inactivated by N-bromosuccinimide and 2-hydroxy-5-nitrobenzyl bromide, and was not affected by p-chloromercuribenzoate, N-acetylimidazole, p-diazobenzenesulfonic acid and tetranitromethane. From these results, tryptophan was estimated to play an important role in the enzyme activity. 3. The apparent molecular weight was 310000 by Sephadex G-200 gel filtration. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate suggested that the molecular weight of the subunit was approximately 89000. 4. The purified enzyme contained 29% carbohydrate consisting of glucosamine, mannose and galactose. The amino acid composition of this enzyme was not specific compared with other known acid phosphatases."}
{"id": "PMID:13844", "title": "Cell-specific differences in membrane beta-glucosidase from normal and Gaucher cells.", "content": "Two isozymes of membrane-bound beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) with activity towards 4-methylumbelliferyl-beta-D-glucopyranoside have been identified in human cells. One of these isozymes was found to have a pH optimum of 5.0, a Km of 0.4 mM and to be rapidly inactivated at pH 4.0 (\"acid-labile\"). The second isozyme had a pH optimum of 4.5, a Km of 0.8 mM and was stable at pH 4.0 (\"acid-stable\"). Cultured long-term lymphoid lines and peripheral blood leukocytes contained both isozymes while cultured skin fibroblasts contained only the \"acid-stable\" form in detectable amounts. The specific activity of the \"acid-stable\" isozyme was severely reduced in cultured skin fibroblasts, cultured long-term lines and peripheral leukocytes from patients with Gaucher's disease. The specific activity of the \"acid-labile\" enzyme in the latter two cell types was apparently unaffected. The beta-glucosidase activity in all three cell types examined was predominantly particulate but the enzyme could be solubilized with low concentrations of Triton X-100. The solubilized enzyme required sodium taurocholate (0.2%) for maximum activity. Solubilized beta-glucosidase did not exhibit the cell-specific differences in pH optimum and Km shown by the membrane-bound enzyme.", "contents": "Cell-specific differences in membrane beta-glucosidase from normal and Gaucher cells. Two isozymes of membrane-bound beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) with activity towards 4-methylumbelliferyl-beta-D-glucopyranoside have been identified in human cells. One of these isozymes was found to have a pH optimum of 5.0, a Km of 0.4 mM and to be rapidly inactivated at pH 4.0 (\"acid-labile\"). The second isozyme had a pH optimum of 4.5, a Km of 0.8 mM and was stable at pH 4.0 (\"acid-stable\"). Cultured long-term lymphoid lines and peripheral blood leukocytes contained both isozymes while cultured skin fibroblasts contained only the \"acid-stable\" form in detectable amounts. The specific activity of the \"acid-stable\" isozyme was severely reduced in cultured skin fibroblasts, cultured long-term lines and peripheral leukocytes from patients with Gaucher's disease. The specific activity of the \"acid-labile\" enzyme in the latter two cell types was apparently unaffected. The beta-glucosidase activity in all three cell types examined was predominantly particulate but the enzyme could be solubilized with low concentrations of Triton X-100. The solubilized enzyme required sodium taurocholate (0.2%) for maximum activity. Solubilized beta-glucosidase did not exhibit the cell-specific differences in pH optimum and Km shown by the membrane-bound enzyme."}
{"id": "PMID:13845", "title": "Benzamidine as an inhibitor of proacrosin activation in bull sperm.", "content": "Epididymal and ejaculated sperm contain a zymogen form of acrosin (acrosomal proteinase, EC 3.4.21.10) which is converted to active enzyme prior to fertilization. Benzamidine at concentrations greater than 10 mM has been shown to inhibit the conversion of proacrosin to acrosin. Based on this inhibition, a procedure was developed for extracting and quantitating the proacrosin content of bull sperm. Sperm were isolated from semen and washed by centrifugation through 1.3 M sucrose and the outer acrosomal membrane removed by homogenization. When 25 mM benzamidine was added to the semen and wash solutions, 98% or more of the acrosin activity in the sperm homogenate was present as proacrosin. Proacrosin can be extracted from the sperm homogenate by dialysis at pH 3, which solubilized the proenzyme and removed benzamidine. Benzamidine has been useful in isolating proacrosin and provides a new method for studying the activation of proacrosin in intact sperm. Neutralization of sperm extracts, after removal of benzamidine, resulted in rapid activation of proacrosin with a pH optimum of 8.5, and activation was complete within 15 min over a pH range of 7.0 to 9.5. Rapid activation also occurred during the washing of sperm in the absence of benzamidine, and this activation correlated with a swelling of the acrosomal membrane. This rapid activation appears to result from a small amount of acrosin activity consistently present in the sperm extract. These results indicate an autocatalytic conversion of proacrosin to acrosin and suggest that disruption of the acrosomal membrane may trigger this activation.", "contents": "Benzamidine as an inhibitor of proacrosin activation in bull sperm. Epididymal and ejaculated sperm contain a zymogen form of acrosin (acrosomal proteinase, EC 3.4.21.10) which is converted to active enzyme prior to fertilization. Benzamidine at concentrations greater than 10 mM has been shown to inhibit the conversion of proacrosin to acrosin. Based on this inhibition, a procedure was developed for extracting and quantitating the proacrosin content of bull sperm. Sperm were isolated from semen and washed by centrifugation through 1.3 M sucrose and the outer acrosomal membrane removed by homogenization. When 25 mM benzamidine was added to the semen and wash solutions, 98% or more of the acrosin activity in the sperm homogenate was present as proacrosin. Proacrosin can be extracted from the sperm homogenate by dialysis at pH 3, which solubilized the proenzyme and removed benzamidine. Benzamidine has been useful in isolating proacrosin and provides a new method for studying the activation of proacrosin in intact sperm. Neutralization of sperm extracts, after removal of benzamidine, resulted in rapid activation of proacrosin with a pH optimum of 8.5, and activation was complete within 15 min over a pH range of 7.0 to 9.5. Rapid activation also occurred during the washing of sperm in the absence of benzamidine, and this activation correlated with a swelling of the acrosomal membrane. This rapid activation appears to result from a small amount of acrosin activity consistently present in the sperm extract. These results indicate an autocatalytic conversion of proacrosin to acrosin and suggest that disruption of the acrosomal membrane may trigger this activation."}
{"id": "PMID:13846", "title": "Studies on aspartase. IV. Reversible denaturation of Escherichia coli aspartase.", "content": "Aspartase (L-aspartate ammonia lyase, EC 4.3.1.1) of Escherichia coli, denatured in 4 M guanidine-HCl, was renatured in vitro by simple dilution with a concomitant restoration of the activity. While the native enzyme exhibited a marked negative Cotton effect centered at 233 +/- 1 nm in optical rotatory dispersion, the enzyme denatured in 4 M guanidine-HCl retained little optical activity. Upon dilution of the denatured enzyme, however, more than 90% of the ordered structure was recovered in 1 min, while the restoration of the activity proceeded much more slowly. Estimation of molecular weights by gel permeation chromatography indicated that the tetrameric enzyme is subject to reversible dissociation into monomeric subunits under the experimental conditions. Various environmental factors such as temperature, pH and protein concentration exhibited profound influence on the rate and extent of the reactivation. In order to examine the correlation between the restoration of the activity and the quaternary structure, electron microscopic inspection of the kinetic processes of reversible denaturation was attempted. Upon dilution of the denatured enzyme at 4 degrees C, neither the activity nor tetrameric images were detected over several min. Upon the temperature shift up to 25 degrees C, however, the activity regain was rapidly proceeded concomitant with the appearance of tetrameric molecules. These results are compatible with the possibility that the subunit assembly is an essential prerequisite, thought not sufficient, for enzyme activity.", "contents": "Studies on aspartase. IV. Reversible denaturation of Escherichia coli aspartase. Aspartase (L-aspartate ammonia lyase, EC 4.3.1.1) of Escherichia coli, denatured in 4 M guanidine-HCl, was renatured in vitro by simple dilution with a concomitant restoration of the activity. While the native enzyme exhibited a marked negative Cotton effect centered at 233 +/- 1 nm in optical rotatory dispersion, the enzyme denatured in 4 M guanidine-HCl retained little optical activity. Upon dilution of the denatured enzyme, however, more than 90% of the ordered structure was recovered in 1 min, while the restoration of the activity proceeded much more slowly. Estimation of molecular weights by gel permeation chromatography indicated that the tetrameric enzyme is subject to reversible dissociation into monomeric subunits under the experimental conditions. Various environmental factors such as temperature, pH and protein concentration exhibited profound influence on the rate and extent of the reactivation. In order to examine the correlation between the restoration of the activity and the quaternary structure, electron microscopic inspection of the kinetic processes of reversible denaturation was attempted. Upon dilution of the denatured enzyme at 4 degrees C, neither the activity nor tetrameric images were detected over several min. Upon the temperature shift up to 25 degrees C, however, the activity regain was rapidly proceeded concomitant with the appearance of tetrameric molecules. These results are compatible with the possibility that the subunit assembly is an essential prerequisite, thought not sufficient, for enzyme activity."}
{"id": "PMID:13847", "title": "Inhibition of sterol synthesis by citrinin in a cell-free system from rat liver and yeast.", "content": "Citrinin, a fungal metabolite known as an antibiotic, strongly inhibited the labeled acetate incorporation into nonsaponifiable lipids by a cell-free system from rat liver but not the labeled mevalonate incorporation. Of the enzymes involved in cholesterol synthesis, two enzymes, acetoacetyl-CoA thiolase (EC 2.3.1.9) and 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34), were specifically inhibited by the antibiotic. The concentration required for 50% inhibition was 0.2 mM for the former enzyme and 0.5 mM for the latter. Essentially the same results were obtained with a cell-free system from yeast although higher concentrations of the antibiotic were required for inhibition.", "contents": "Inhibition of sterol synthesis by citrinin in a cell-free system from rat liver and yeast. Citrinin, a fungal metabolite known as an antibiotic, strongly inhibited the labeled acetate incorporation into nonsaponifiable lipids by a cell-free system from rat liver but not the labeled mevalonate incorporation. Of the enzymes involved in cholesterol synthesis, two enzymes, acetoacetyl-CoA thiolase (EC 2.3.1.9) and 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34), were specifically inhibited by the antibiotic. The concentration required for 50% inhibition was 0.2 mM for the former enzyme and 0.5 mM for the latter. Essentially the same results were obtained with a cell-free system from yeast although higher concentrations of the antibiotic were required for inhibition."}
{"id": "PMID:13848", "title": "Effects of divalent cations and sodium taurocholate on pancreatic lipase activity with gum arabic-emulsified tributyrylglycerol substrates.", "content": "The effects of Ca2+ and/or sodium taurocholate on lipase activity with gum arabic-emulsified tributyrylglycerol substrates were investigated. Calcium was found to slightly increase lipase activity while bile salts showed marked inhibition except at very low concentrations. Calcium eliminated inhibition seen with low concentrations of bile salts and reduced the inhibition seen at higher bile shift of the enzyme from the alkaline region in the absence of bile salt to the slightly acidic region in the presence of bile salt. Calcium was shown to eliminate the time lag periods between enzyme addition and maximum rate of hydrolysis seen at low substrate concentrations and the time lag noted when bile salts were included with normal (substrate concentration not limiting) assay concentrations of substrate. Zeta potential measurements indicated that Ca2+ reduced the negative charge on the gum arabic-emulsified particle while bile salts did not increase the negative charge. Commercial preparations of gum arabic were found to have significant concentrations of Ca2+ and Mg2+.", "contents": "Effects of divalent cations and sodium taurocholate on pancreatic lipase activity with gum arabic-emulsified tributyrylglycerol substrates. The effects of Ca2+ and/or sodium taurocholate on lipase activity with gum arabic-emulsified tributyrylglycerol substrates were investigated. Calcium was found to slightly increase lipase activity while bile salts showed marked inhibition except at very low concentrations. Calcium eliminated inhibition seen with low concentrations of bile salts and reduced the inhibition seen at higher bile shift of the enzyme from the alkaline region in the absence of bile salt to the slightly acidic region in the presence of bile salt. Calcium was shown to eliminate the time lag periods between enzyme addition and maximum rate of hydrolysis seen at low substrate concentrations and the time lag noted when bile salts were included with normal (substrate concentration not limiting) assay concentrations of substrate. Zeta potential measurements indicated that Ca2+ reduced the negative charge on the gum arabic-emulsified particle while bile salts did not increase the negative charge. Commercial preparations of gum arabic were found to have significant concentrations of Ca2+ and Mg2+."}
{"id": "PMID:13849", "title": "Soluble rat adipocyte phosphatidate phosphatase activity: characterization and effects of fasting and various lipids.", "content": "Phosphatidate phosphatase (phosphatidate phosphohydrolase, EC 3.1.3.4) was present at very high specific activity in the soluble fraction of isolated rat adipocytes. Using phosphatidate in aqueous dispersion 90% of its hydrolysis depended on the presence of Mg2+. Mg2+ appeared to almost saturate the enzyme at 20-40 mM with no indication of an optimum. The substrate concentration was optimum at 1.2 mM and the pH at 6.8. Initial rates were linear for only 4-5 min at optimum conditions. Increasing inhibition occurred at high phosphatidate concentrations. At optimum conditions acid or alkaline phosphatase activity was not measurable. The Mg2+-dependent activity was enhanced by 3-sn-phophatidylcholine and inhibited by albumin, 3-sn-phosphatidyletanolamine, 3-sn-phosphatidylinositol, diacylglycerol, oleoyl-CoA, and oleate. Oleoyl-CoA was the most potent \"effector\". Fasting for 24, 48 and 72 h decreased the activity both relative to protein and to DNA. The activity thus decreased to about one-third of that of the fed rat during 72 h of fasting. The effects of Mg2+, various lipids, and fasting may indicate that some form of control of glyceride synthesis can be exerted through the soluble phosphatidate phosphatase.", "contents": "Soluble rat adipocyte phosphatidate phosphatase activity: characterization and effects of fasting and various lipids. Phosphatidate phosphatase (phosphatidate phosphohydrolase, EC 3.1.3.4) was present at very high specific activity in the soluble fraction of isolated rat adipocytes. Using phosphatidate in aqueous dispersion 90% of its hydrolysis depended on the presence of Mg2+. Mg2+ appeared to almost saturate the enzyme at 20-40 mM with no indication of an optimum. The substrate concentration was optimum at 1.2 mM and the pH at 6.8. Initial rates were linear for only 4-5 min at optimum conditions. Increasing inhibition occurred at high phosphatidate concentrations. At optimum conditions acid or alkaline phosphatase activity was not measurable. The Mg2+-dependent activity was enhanced by 3-sn-phophatidylcholine and inhibited by albumin, 3-sn-phosphatidyletanolamine, 3-sn-phosphatidylinositol, diacylglycerol, oleoyl-CoA, and oleate. Oleoyl-CoA was the most potent \"effector\". Fasting for 24, 48 and 72 h decreased the activity both relative to protein and to DNA. The activity thus decreased to about one-third of that of the fed rat during 72 h of fasting. The effects of Mg2+, various lipids, and fasting may indicate that some form of control of glyceride synthesis can be exerted through the soluble phosphatidate phosphatase."}
{"id": "PMID:13850", "title": "Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala: isolation and functional properties of the heme saturated form.", "content": "Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala is a neutrally substituted unstable hemoglobin, exhibiting the same gross features as hemoglobin K\u00f6ln beta98 (FG 5) Val leads to Met. In addition to the presence of a deheminized fraction, a heme saturated abnormal hemoglobin was visualized and isolated by high resolution electrofocusing. By functional studies of the fully heminized form, a slightly increased oxygen affinity, an impairment of heme-heme interaction and a decreased response to organic phosphates were demonstrated. These functional perturbations point out the importance of the beta98 invariant valyl residue, in the quaternary contacts. They can account for the poor oxygen delivery of erythrocytes.", "contents": "Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala: isolation and functional properties of the heme saturated form. Hemoglobin Djelfa beta98 (FG 5) Val leads to Ala is a neutrally substituted unstable hemoglobin, exhibiting the same gross features as hemoglobin K\u00f6ln beta98 (FG 5) Val leads to Met. In addition to the presence of a deheminized fraction, a heme saturated abnormal hemoglobin was visualized and isolated by high resolution electrofocusing. By functional studies of the fully heminized form, a slightly increased oxygen affinity, an impairment of heme-heme interaction and a decreased response to organic phosphates were demonstrated. These functional perturbations point out the importance of the beta98 invariant valyl residue, in the quaternary contacts. They can account for the poor oxygen delivery of erythrocytes."}
{"id": "PMID:13851", "title": "Functional properties of partially oxidized trout hemoglobins.", "content": "This paper reports on a study of the effect of partial oxidation on oxygen and carbon monoxide binding by components I and IV of trout hemoglobin. The O2 binding equilibria of the various oxidation mixtures show a decrease in the heme-heme interactions as the number of oxidized sites is increased. However, the large Bohr effect, characteristic of Hb Trout IV, is maintained unchanged. Similarly the time course of CO combination changes on increasing the fractional oxidation, and the autocatalytic character of the CO binding kinetics is lost; however the pH dependence of the apparent \"on\" constant in the oxidation mixtures is similar to that characteristic of the native molecule. The results of the O2 equilibria and of CO binding kinetics may be interpreted in accordance with the two state concerted model suggesting that in the oxidation intermediates there is an increase in the fraction of the high affinity (R) conformation. Additional experiments on the effect of azide, and fluoride, ferric ligands which produce a change of spin state of the heme iron, suggest that additional second order conformational changes may also come into play.", "contents": "Functional properties of partially oxidized trout hemoglobins. This paper reports on a study of the effect of partial oxidation on oxygen and carbon monoxide binding by components I and IV of trout hemoglobin. The O2 binding equilibria of the various oxidation mixtures show a decrease in the heme-heme interactions as the number of oxidized sites is increased. However, the large Bohr effect, characteristic of Hb Trout IV, is maintained unchanged. Similarly the time course of CO combination changes on increasing the fractional oxidation, and the autocatalytic character of the CO binding kinetics is lost; however the pH dependence of the apparent \"on\" constant in the oxidation mixtures is similar to that characteristic of the native molecule. The results of the O2 equilibria and of CO binding kinetics may be interpreted in accordance with the two state concerted model suggesting that in the oxidation intermediates there is an increase in the fraction of the high affinity (R) conformation. Additional experiments on the effect of azide, and fluoride, ferric ligands which produce a change of spin state of the heme iron, suggest that additional second order conformational changes may also come into play."}
{"id": "PMID:13852", "title": "Equilibrium and kinetics of the unfolding of alpha-lactalbumin by guanidine hydrochloride (IV): dependence of the N equilibrium A transconformation on the temperature.", "content": "The reversible unfolding from the native (N) state to the acid (A) state of alpha-lactalbumin by guanidine-HCl (0.8-2.0 M) was studied at 10-35 degrees C by means of difference spectra and pH-jump measurements. At each temperature, all points plotted as the logarithmic equilibrium constant log KNA of the N equilibrium A process against pH could fall on a curve independent of the denaturant concentration by shifting each point along the log KNA axis, where the shift factor f did not depend on temperature. Moreover, by shifting the points at each temperature along the log (KNA/f) axis, a master curve, independent of both temperature and the denaturant concentration, could be obtained for the pH-dependence of log KNA. From the dependence of the logarithmic rate constants on pH, master curves independent of both temperature and the denaturant concentration could also be made for the N leads to A and the A leads to A processes, where A mean the activated state. The results show the two-state character of the N equilibrium A process. The enthalpy changes and the differences in heat capacity for the N equilibrium A, N equilibrium A and A equilibrium A processes were determined from the accurate measurements of temperature dependence of the unfolding at pH 4.3 and 1.0 M guanidine-HCl. The results show that the disruption of hydrophobic interaction is caused mainly in the A leads to A process, while most of the changes in the pK values of the ionizing groups are caused in the N leads to A process.", "contents": "Equilibrium and kinetics of the unfolding of alpha-lactalbumin by guanidine hydrochloride (IV): dependence of the N equilibrium A transconformation on the temperature. The reversible unfolding from the native (N) state to the acid (A) state of alpha-lactalbumin by guanidine-HCl (0.8-2.0 M) was studied at 10-35 degrees C by means of difference spectra and pH-jump measurements. At each temperature, all points plotted as the logarithmic equilibrium constant log KNA of the N equilibrium A process against pH could fall on a curve independent of the denaturant concentration by shifting each point along the log KNA axis, where the shift factor f did not depend on temperature. Moreover, by shifting the points at each temperature along the log (KNA/f) axis, a master curve, independent of both temperature and the denaturant concentration, could be obtained for the pH-dependence of log KNA. From the dependence of the logarithmic rate constants on pH, master curves independent of both temperature and the denaturant concentration could also be made for the N leads to A and the A leads to A processes, where A mean the activated state. The results show the two-state character of the N equilibrium A process. The enthalpy changes and the differences in heat capacity for the N equilibrium A, N equilibrium A and A equilibrium A processes were determined from the accurate measurements of temperature dependence of the unfolding at pH 4.3 and 1.0 M guanidine-HCl. The results show that the disruption of hydrophobic interaction is caused mainly in the A leads to A process, while most of the changes in the pK values of the ionizing groups are caused in the N leads to A process."}
{"id": "PMID:13853", "title": "Studies on biotransformation of lysozyme. III. Comparative studies on biotransformation of exogenous and endogenous lysozyme in rats.", "content": "Exogenous hen lysozyme or endogenous rat lysozyme labeled with 131I was intravenously injected to rats with the same dosage, respectively, and the uptake and degradation of injected 131I-labeled rat lysozyme in liver and kidney were studied in comparison with those of 131I-labeled hen lysozyme. 1. Although the serum levels of both enzymes injected were almost indentical during the first 6 h, the liver uptake of 131I-labeled hen lysozyme was 2.2-fold more than that of 131I-labeled rat lysozyme at the peak time of 5 min after injection. The uptake and clearance of 131I-labeled rat lysozyme in the kidney were exclusively slow as compared with those of 131I-labeled hen lysozyme. 2. The intracellular distribution in the liver and kidney were examined by the differential centrifugation after injection of each lysozyme. The protein-bound radioactivity of each subcellular fraction was found to be the highest in the 12 000 X g (10 min) fraction in the liver and the 19 600 X g (20 min) fraction in the kidney. The relative specific activity of 12 000 X g fraction of the liver after injection increased with the time lapse. On the other hand, the relative specific activity of 105 000 X g (1 h) fraction of the liver attained a maximum within 5 min after injection and thereafter decreased. It was assumed that the mechanism of the uptake of injected 131I-labeled rat lysozyme in the liver and kidney was similar to that of 131I-labeled hen lysozyme. 3. The degradation of exogenous or endogenous lysozyme in subcellular particles was examined. From the effect of pH, activator and inhibitor on the degradation, the proteolytic enzyme to degrade the injected 131I-labeled hen lysozyme was indicated to be mainly cathepsin BL, with the optimal pH of about 5.0, and the injected 131I-labeled rate lysozyme was mainly degraded by cathepsin D, with the optimal pH of about 3.5 The in vitro degradation of exogenous and endogenous lysozymes showed a tendency similar to the in vivo clearance from the liver and kidney.", "contents": "Studies on biotransformation of lysozyme. III. Comparative studies on biotransformation of exogenous and endogenous lysozyme in rats. Exogenous hen lysozyme or endogenous rat lysozyme labeled with 131I was intravenously injected to rats with the same dosage, respectively, and the uptake and degradation of injected 131I-labeled rat lysozyme in liver and kidney were studied in comparison with those of 131I-labeled hen lysozyme. 1. Although the serum levels of both enzymes injected were almost indentical during the first 6 h, the liver uptake of 131I-labeled hen lysozyme was 2.2-fold more than that of 131I-labeled rat lysozyme at the peak time of 5 min after injection. The uptake and clearance of 131I-labeled rat lysozyme in the kidney were exclusively slow as compared with those of 131I-labeled hen lysozyme. 2. The intracellular distribution in the liver and kidney were examined by the differential centrifugation after injection of each lysozyme. The protein-bound radioactivity of each subcellular fraction was found to be the highest in the 12 000 X g (10 min) fraction in the liver and the 19 600 X g (20 min) fraction in the kidney. The relative specific activity of 12 000 X g fraction of the liver after injection increased with the time lapse. On the other hand, the relative specific activity of 105 000 X g (1 h) fraction of the liver attained a maximum within 5 min after injection and thereafter decreased. It was assumed that the mechanism of the uptake of injected 131I-labeled rat lysozyme in the liver and kidney was similar to that of 131I-labeled hen lysozyme. 3. The degradation of exogenous or endogenous lysozyme in subcellular particles was examined. From the effect of pH, activator and inhibitor on the degradation, the proteolytic enzyme to degrade the injected 131I-labeled hen lysozyme was indicated to be mainly cathepsin BL, with the optimal pH of about 5.0, and the injected 131I-labeled rate lysozyme was mainly degraded by cathepsin D, with the optimal pH of about 3.5 The in vitro degradation of exogenous and endogenous lysozymes showed a tendency similar to the in vivo clearance from the liver and kidney."}
{"id": "PMID:13854", "title": "The binding of calcium to bovine fibrinogen.", "content": "The determination of the number of calcium binding sites of fibrinogen was carried out by means of equilibrium experiments. At pH 7.5 fibrinogen has 3 binding sites of high affinity and several binding sites of low affinity. In the presence of MgCl2 (10(-2)M) the sites of low affinity are eliminated, suggesting that they are not specific and due to weak interactions. Study of the effect of the pH have demonstrated that the 3 sites of high affinity are not identical. At pH values below 7.5 one site is eliminated. This could be due either to an abnormal protonation or to a conformational change. No cooperativity between the sites was found. Partial identification of the binding site by means of direct titration of the calcium induced proton release have shown that the calcium is tightly bound through a chelate system. From the apparent dissociation constant obtained a possible involvement of histidine residues in this chelate system is suggested.", "contents": "The binding of calcium to bovine fibrinogen. The determination of the number of calcium binding sites of fibrinogen was carried out by means of equilibrium experiments. At pH 7.5 fibrinogen has 3 binding sites of high affinity and several binding sites of low affinity. In the presence of MgCl2 (10(-2)M) the sites of low affinity are eliminated, suggesting that they are not specific and due to weak interactions. Study of the effect of the pH have demonstrated that the 3 sites of high affinity are not identical. At pH values below 7.5 one site is eliminated. This could be due either to an abnormal protonation or to a conformational change. No cooperativity between the sites was found. Partial identification of the binding site by means of direct titration of the calcium induced proton release have shown that the calcium is tightly bound through a chelate system. From the apparent dissociation constant obtained a possible involvement of histidine residues in this chelate system is suggested."}
{"id": "PMID:13855", "title": "Organic phosphate binding to hemoglobin in intact human erythrocytes determined by 31P nuclear magnetic resonance spectroscopy.", "content": "Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy was used to estimate the percent of 2,3-diphosphoglycerate and ATP bound to hemoglobin in intact human erythrocytes at 37 degrees C. Binding was assessed by comparing the chemical shifts (delta) of 2,3-diphosphoglycerate and of ATP observed in intact cells with the delta values of these organic phosphates determined in model solutions closely simulating intracellular conditions, in which percent binding was directly evaluated by membrane ultrafiltration. The results showed that the percent of bound 2,3-diphosphoglycerate in intact cells varied with pH, the state of oxygenation, and 2,3-diphosphoglycerate concentration. The values ranged from 33% in cells incubated with glucose in air at an intracellular pH of 7.2 to 100% in cells incubated with inosine in N2 at a pH of 6.75. At the same 2,3-diphosphoglycerate concentration, a greater percentage of the compound appeared to be bound in erythrocytes than in the closely simulated model system. ATP was not significantly bound to hemoglobin under any condition examined, but appeared to be strongly complexed to Mg2+ inside the erythrocyte. The binding percentages for both 2,3-diphosphoglycerate and ATP in intact cells estimated by 31P NMR spectroscopy were lower than those calculated by others from individual association constants determined for the binding of different ligands to hemoglobin.", "contents": "Organic phosphate binding to hemoglobin in intact human erythrocytes determined by 31P nuclear magnetic resonance spectroscopy. Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy was used to estimate the percent of 2,3-diphosphoglycerate and ATP bound to hemoglobin in intact human erythrocytes at 37 degrees C. Binding was assessed by comparing the chemical shifts (delta) of 2,3-diphosphoglycerate and of ATP observed in intact cells with the delta values of these organic phosphates determined in model solutions closely simulating intracellular conditions, in which percent binding was directly evaluated by membrane ultrafiltration. The results showed that the percent of bound 2,3-diphosphoglycerate in intact cells varied with pH, the state of oxygenation, and 2,3-diphosphoglycerate concentration. The values ranged from 33% in cells incubated with glucose in air at an intracellular pH of 7.2 to 100% in cells incubated with inosine in N2 at a pH of 6.75. At the same 2,3-diphosphoglycerate concentration, a greater percentage of the compound appeared to be bound in erythrocytes than in the closely simulated model system. ATP was not significantly bound to hemoglobin under any condition examined, but appeared to be strongly complexed to Mg2+ inside the erythrocyte. The binding percentages for both 2,3-diphosphoglycerate and ATP in intact cells estimated by 31P NMR spectroscopy were lower than those calculated by others from individual association constants determined for the binding of different ligands to hemoglobin."}
{"id": "PMID:13856", "title": "Hemoglobin Tarrant: alpha126(H9) Asp leads to Asn. A new hemoglobin variant in the alpha1beta1 contact region showing high oxygen affinity and reduced cooperativity.", "content": "Hemoglobin (Hb) Tarrant was detected by its electrophoretic mobility on cellulose acetate (pH 8.4) and citrate agar (pH 6.2). On cellulose acetate it moved as a band between hemoglobins F and S, and on citrate agar as a band at hemoglobin S. The test for solubility in 2 M phosphate buffer with Na2S2O4 was negative. The new variant has a substitution of asparagine for aspartic acid in position 126 of the alpha-chain, one of the sites involved in the alpha1beta1 contact.  Furthermore, in deoxyhemoglobin aspartic acid 126 of each alpha chain also forms a non-covalent electrostatic salt bridge with arginine 141 of the corresponding alpha chain (Perutz, M. F. and Ten Eyck, L. F. (1972) Cold Spring Harbor Symp. Quant. Biol. 36, 295-310 and Perutz, M. F. (1970) Nature 228, 726-739). As a consequence of this substitution in hemoglobin Tarrant, the deoxy conformation or T state is destabilized because these two bridges cannot be formed. This condition is reflected in high oxygen affinity and low cooperativity.", "contents": "Hemoglobin Tarrant: alpha126(H9) Asp leads to Asn. A new hemoglobin variant in the alpha1beta1 contact region showing high oxygen affinity and reduced cooperativity. Hemoglobin (Hb) Tarrant was detected by its electrophoretic mobility on cellulose acetate (pH 8.4) and citrate agar (pH 6.2). On cellulose acetate it moved as a band between hemoglobins F and S, and on citrate agar as a band at hemoglobin S. The test for solubility in 2 M phosphate buffer with Na2S2O4 was negative. The new variant has a substitution of asparagine for aspartic acid in position 126 of the alpha-chain, one of the sites involved in the alpha1beta1 contact.  Furthermore, in deoxyhemoglobin aspartic acid 126 of each alpha chain also forms a non-covalent electrostatic salt bridge with arginine 141 of the corresponding alpha chain (Perutz, M. F. and Ten Eyck, L. F. (1972) Cold Spring Harbor Symp. Quant. Biol. 36, 295-310 and Perutz, M. F. (1970) Nature 228, 726-739). As a consequence of this substitution in hemoglobin Tarrant, the deoxy conformation or T state is destabilized because these two bridges cannot be formed. This condition is reflected in high oxygen affinity and low cooperativity."}
{"id": "PMID:13857", "title": "The gamma-carboxy glutamic acid content of human and bovine prothrombin following warfarin treatment.", "content": "A form of prothrombin induced by Warfarin therapy, has been isolated which is adsorbed onto insoluble barium salts, but has a reduced biological activity. This protein contains, on average, seven out of a possible ten gamma-carboxy glutamic acid residues. A second form of prothrombin is also described, which is not adsorbed into barium slats, and has less than 1% the activity of the normal protein, contains only four gamma-carboxy glutamic acid residues. The significance of these results is discussed.", "contents": "The gamma-carboxy glutamic acid content of human and bovine prothrombin following warfarin treatment. A form of prothrombin induced by Warfarin therapy, has been isolated which is adsorbed onto insoluble barium salts, but has a reduced biological activity. This protein contains, on average, seven out of a possible ten gamma-carboxy glutamic acid residues. A second form of prothrombin is also described, which is not adsorbed into barium slats, and has less than 1% the activity of the normal protein, contains only four gamma-carboxy glutamic acid residues. The significance of these results is discussed."}
{"id": "PMID:13858", "title": "Iionization of tyrosyl groups of ovalbumin under native and denaturing conditions.", "content": "Phenolic titration of ovalbumin was performed in the pH range 7-12 at 30 degrees C and at three ionic strengths viz. 0.033, 0.133 and 0.200. The conformational integrity of ovalbumin was studied by viscosity measurements at different pH values in the pH range 7-12.4. At ionic strength 0.133 two phenolic groups titrated reversibly with pKint = 10.31, and w = 0.032 up to pH 11.25 under native conditions. The value of w expectedly decreased with increase in ionic strength. Two additional phenolic groups became available for reversible titration between pH 11.25 and 11.95 after some conformational change. Above pH 12, the phenolic titration became irreversible and all of the nine tyrosine residues were titrated at pH 13.3 Exposure of ovalbumin to alkaline pH (12.4) caused considerable disruption of the native protein conformation. The reduced viscosity increased from 4.2 ml/g at pH 7.0 to 16.8 ml/g at pH 12.4 under identical conditions of the protein concentration. All of the nine tyrosyl groups of ovalbumin were titrated normally (pKint = 9.9) in a mixture of 5 M guanidine hydrochloride and 1.2 M urea. However, even in this mixture electrostatic interaction, as measured by w was not completely abolished.", "contents": "Iionization of tyrosyl groups of ovalbumin under native and denaturing conditions. Phenolic titration of ovalbumin was performed in the pH range 7-12 at 30 degrees C and at three ionic strengths viz. 0.033, 0.133 and 0.200. The conformational integrity of ovalbumin was studied by viscosity measurements at different pH values in the pH range 7-12.4. At ionic strength 0.133 two phenolic groups titrated reversibly with pKint = 10.31, and w = 0.032 up to pH 11.25 under native conditions. The value of w expectedly decreased with increase in ionic strength. Two additional phenolic groups became available for reversible titration between pH 11.25 and 11.95 after some conformational change. Above pH 12, the phenolic titration became irreversible and all of the nine tyrosine residues were titrated at pH 13.3 Exposure of ovalbumin to alkaline pH (12.4) caused considerable disruption of the native protein conformation. The reduced viscosity increased from 4.2 ml/g at pH 7.0 to 16.8 ml/g at pH 12.4 under identical conditions of the protein concentration. All of the nine tyrosyl groups of ovalbumin were titrated normally (pKint = 9.9) in a mixture of 5 M guanidine hydrochloride and 1.2 M urea. However, even in this mixture electrostatic interaction, as measured by w was not completely abolished."}
{"id": "PMID:13859", "title": "Latency of microsomal hexose-6-phosphate dehydrogenase activity.", "content": "Intact microsomes isolated from rat liver showed no hexose-6-phosphate dehydrogenase activity, but the enzyme was activated by Triton X-100, deoxycholate, NH4OH, glycine/NaOH, lysophosphatidylcholine, phospholipases A and C, pancreatic lipase and cholesterol esterase, and also by sonic treatment. The enzyme activation by deoxycholate, NH4OH and sonic treatments was solely due to solubilization, while that by phospholipase A appeared to be due to the detergent action of the hydrolysis products. On the other hand, the primary effects of phospholipase C, cholesterol esterase and pancreatic lipase might be accounted for by the partial removal of membrane lipids. The results of washing and trypsin digestion experiments suggested that hexose-6-phosphate dehydrogenase is one of the most firmly bound enzymes among the microsomal proteins. The catalytic properties were the same in the solubilized and the membrane-bound, activated enzymes. Feeding the rats on a high carbohydrate diet altered the extent of enzyme activation by sonication and phospholipase C treatment, suggesting that the microsomal membrane would actually undergo changes in the conformation and/or chemical composition under certain circumstances.", "contents": "Latency of microsomal hexose-6-phosphate dehydrogenase activity. Intact microsomes isolated from rat liver showed no hexose-6-phosphate dehydrogenase activity, but the enzyme was activated by Triton X-100, deoxycholate, NH4OH, glycine/NaOH, lysophosphatidylcholine, phospholipases A and C, pancreatic lipase and cholesterol esterase, and also by sonic treatment. The enzyme activation by deoxycholate, NH4OH and sonic treatments was solely due to solubilization, while that by phospholipase A appeared to be due to the detergent action of the hydrolysis products. On the other hand, the primary effects of phospholipase C, cholesterol esterase and pancreatic lipase might be accounted for by the partial removal of membrane lipids. The results of washing and trypsin digestion experiments suggested that hexose-6-phosphate dehydrogenase is one of the most firmly bound enzymes among the microsomal proteins. The catalytic properties were the same in the solubilized and the membrane-bound, activated enzymes. Feeding the rats on a high carbohydrate diet altered the extent of enzyme activation by sonication and phospholipase C treatment, suggesting that the microsomal membrane would actually undergo changes in the conformation and/or chemical composition under certain circumstances."}
{"id": "PMID:13860", "title": "Binding protein for 5 alpha-dihydrotestosterone in mouse submandibular gland.", "content": "The changes in the levels of the binding protein for 5 alpha-dihydrotestosterone in cytoplasmic extract of the submandibular glands during development were compared in male and female mice using a DEAE-cellulose filter assay. The binding protein was first detectable 5 days after birth in both sexes, at a time coincident with androgen-independent cytodifferentiation of the convoluted tubular cells in the submadibular gland. The level of the binding protein in female mice was maintained at 5 pmol/mg protein after birth, whereas in males it began to decrease from 3 weeks after birth with inccrease in serum testosterone, becoming much less than a quarter of the level in females or immature mice by 4 weeks after birth. However, after castration, the level of detectable binding protein in mature male mice increased within 7 days to the same level as that in females or immature mice. This suggests that the low binding capacity for exogenous hormone in mature male mice is due to occupancy of the binding sites by endogenous hormone.", "contents": "Binding protein for 5 alpha-dihydrotestosterone in mouse submandibular gland. The changes in the levels of the binding protein for 5 alpha-dihydrotestosterone in cytoplasmic extract of the submandibular glands during development were compared in male and female mice using a DEAE-cellulose filter assay. The binding protein was first detectable 5 days after birth in both sexes, at a time coincident with androgen-independent cytodifferentiation of the convoluted tubular cells in the submadibular gland. The level of the binding protein in female mice was maintained at 5 pmol/mg protein after birth, whereas in males it began to decrease from 3 weeks after birth with inccrease in serum testosterone, becoming much less than a quarter of the level in females or immature mice by 4 weeks after birth. However, after castration, the level of detectable binding protein in mature male mice increased within 7 days to the same level as that in females or immature mice. This suggests that the low binding capacity for exogenous hormone in mature male mice is due to occupancy of the binding sites by endogenous hormone."}
{"id": "PMID:13861", "title": "Solubilised intrinsic factor receptor from pig ileum and its characteristics.", "content": "The vitamin B-12-intrinsic factor receptor was shown to be present in pig ileum and localized on the brush borders of the enterocytes, and to be solubilisable with Triton X-100. At neutral pH and in the presence of Ca2+ it bound the vitamin B-12-intrinsic factor but not the vitamin B-12-cobalophilin complex. The solubilised vitamin B-12-intrinsic factor-receptor complex consisted of two molecular species with clear Stokes radii (13.11 and 33.53 nm), sedimentation coefficients (15.1 and 45.1 S) and molecular weights (1 600 000  and 12 000 000). A third smaller macromolecule possibly also represented the receptor. Some receptor activity was present in extracts prepared with buffers lacking detergent. There was evidence that the receptor is a membrane lipoprotein from which the lipids reversibly dissociate. Free intrinsic factor also bound to the solubilized receptor and its vitamin B-12-binding site seemed not to be involved in the attachment to the receptor. A small portion of the vitamin B-12-intrinsic factor spontaneously dissociated from the receptor and nearly all dissociated in the presence of Na2-EDTA. TheStokes radius of the dissociated vitamin B-12-intrinsic factor complex was 0.17 nm smaller than before binding to the receptor. Intrinsic factor and cobalophilin were present in ileal extract and observations were made on their molecular characteristics. These proteins, polymers of the vitamin B-12-intrinsic factor complex and binding of vitamin B-12 and its protein complexes to detergent micelles may give spurious receptor-like effects which must be properly controlled.", "contents": "Solubilised intrinsic factor receptor from pig ileum and its characteristics. The vitamin B-12-intrinsic factor receptor was shown to be present in pig ileum and localized on the brush borders of the enterocytes, and to be solubilisable with Triton X-100. At neutral pH and in the presence of Ca2+ it bound the vitamin B-12-intrinsic factor but not the vitamin B-12-cobalophilin complex. The solubilised vitamin B-12-intrinsic factor-receptor complex consisted of two molecular species with clear Stokes radii (13.11 and 33.53 nm), sedimentation coefficients (15.1 and 45.1 S) and molecular weights (1 600 000  and 12 000 000). A third smaller macromolecule possibly also represented the receptor. Some receptor activity was present in extracts prepared with buffers lacking detergent. There was evidence that the receptor is a membrane lipoprotein from which the lipids reversibly dissociate. Free intrinsic factor also bound to the solubilized receptor and its vitamin B-12-binding site seemed not to be involved in the attachment to the receptor. A small portion of the vitamin B-12-intrinsic factor spontaneously dissociated from the receptor and nearly all dissociated in the presence of Na2-EDTA. TheStokes radius of the dissociated vitamin B-12-intrinsic factor complex was 0.17 nm smaller than before binding to the receptor. Intrinsic factor and cobalophilin were present in ileal extract and observations were made on their molecular characteristics. These proteins, polymers of the vitamin B-12-intrinsic factor complex and binding of vitamin B-12 and its protein complexes to detergent micelles may give spurious receptor-like effects which must be properly controlled."}
{"id": "PMID:13862", "title": "Factors affecting the amount and the activity of the glutamate dehydrogenases of Coprinus cinereus.", "content": "Kinetic analyses done with cell-free extracts of this basidiomycete fungus showed that the NADP-linked glutamate dehydrogenase exhibited positively co-operative interactions with the substrates 2-oxoglutarate and NADPH, negatively co-operative kinetics with NADP+ and was extremely sensitive to inhibition of deamination activity by ammonium and/or ammonia. The NAD-linked enzyme showed positive co-operativity with NADH, Michaelis-Menten kinetics with all other substrates and was subject only to mild inhibitions by the reaction products. Considered together with the values of the Michaelis constants, these results indicate that the former enzyme is primarily concerned with the amination of 2-oxoglutarate when the concentration of this substrate exceeds about 4 mM, while the NAD-linked enzyme is able to aminate or deaminate as metabolic conditions require. Synthesis of both enzymes was repressed by addition of carbamyl phosphate or N-acetyl-glutamate to mycelial cultures growing in media containing glucose and ammonium as carbon and nitrogen sources. Growth in media containing urea results in repression of the NADP-linked glutamate dehydrogenase and derepression of the NAD-linked enzyme. Such results indicate a connexion between the glutamate dehydrogenases and the urea cycle. It is suggested that under normal conditions of growth on complex media nitrogen is assimilated in the form of amino acids and that the glutamate dehydrogenases act in support of transaminases to allow this process to continue, and in support of the urea cycle to allow the disposal of excess nitrogen.", "contents": "Factors affecting the amount and the activity of the glutamate dehydrogenases of Coprinus cinereus. Kinetic analyses done with cell-free extracts of this basidiomycete fungus showed that the NADP-linked glutamate dehydrogenase exhibited positively co-operative interactions with the substrates 2-oxoglutarate and NADPH, negatively co-operative kinetics with NADP+ and was extremely sensitive to inhibition of deamination activity by ammonium and/or ammonia. The NAD-linked enzyme showed positive co-operativity with NADH, Michaelis-Menten kinetics with all other substrates and was subject only to mild inhibitions by the reaction products. Considered together with the values of the Michaelis constants, these results indicate that the former enzyme is primarily concerned with the amination of 2-oxoglutarate when the concentration of this substrate exceeds about 4 mM, while the NAD-linked enzyme is able to aminate or deaminate as metabolic conditions require. Synthesis of both enzymes was repressed by addition of carbamyl phosphate or N-acetyl-glutamate to mycelial cultures growing in media containing glucose and ammonium as carbon and nitrogen sources. Growth in media containing urea results in repression of the NADP-linked glutamate dehydrogenase and derepression of the NAD-linked enzyme. Such results indicate a connexion between the glutamate dehydrogenases and the urea cycle. It is suggested that under normal conditions of growth on complex media nitrogen is assimilated in the form of amino acids and that the glutamate dehydrogenases act in support of transaminases to allow this process to continue, and in support of the urea cycle to allow the disposal of excess nitrogen."}
{"id": "PMID:13863", "title": "The transsulfuration pathway in Tetrahymena pyriformis.", "content": "Four enzymes necessary for the metabolism of methionine by the trans-sulfuration pathway, methionine adenosyltransferase (EC 2.5.1.6), adenosylhomocysteinase (EC 3.3.1.1), cystathionine beta-synthase (EC 4.2.1.22) and cystathionine gamma-lyase (EC 4.4.1.1) were identified in Tetrahymean pyriformis. The ability of these cells to transfer 35S from E135S]methionine to form [35S] cysteine was also observed and taken as direct evidence for the functional existence of this pathway in Tetrahymena. An intermediate in the pathway and an active methyl donor, S-adenosylmethionine, was qualitatively identified in Tetrahymena and its concentration was found to be greater in late stationary phase cells than in early stationary phase cells.", "contents": "The transsulfuration pathway in Tetrahymena pyriformis. Four enzymes necessary for the metabolism of methionine by the trans-sulfuration pathway, methionine adenosyltransferase (EC 2.5.1.6), adenosylhomocysteinase (EC 3.3.1.1), cystathionine beta-synthase (EC 4.2.1.22) and cystathionine gamma-lyase (EC 4.4.1.1) were identified in Tetrahymean pyriformis. The ability of these cells to transfer 35S from E135S]methionine to form [35S] cysteine was also observed and taken as direct evidence for the functional existence of this pathway in Tetrahymena. An intermediate in the pathway and an active methyl donor, S-adenosylmethionine, was qualitatively identified in Tetrahymena and its concentration was found to be greater in late stationary phase cells than in early stationary phase cells."}
{"id": "PMID:13864", "title": "Modulation of the Root effect in goldfish by ATP and GTP.", "content": "Both ATP and GTP are present in considerable amounts in red cells of the common goldfish Carassius auratus. They both influence the Root effect of the single major fish hemoglobin, but GTP is, depending on pH, 2-6 times more effective than ATP. The two triphosphates account for 3/4 of the effect of trichloroacetic acid supernatant obtained from hemolysate which contains still some compound(s) which can influence the shift of the Root effect toward higher pH.", "contents": "Modulation of the Root effect in goldfish by ATP and GTP. Both ATP and GTP are present in considerable amounts in red cells of the common goldfish Carassius auratus. They both influence the Root effect of the single major fish hemoglobin, but GTP is, depending on pH, 2-6 times more effective than ATP. The two triphosphates account for 3/4 of the effect of trichloroacetic acid supernatant obtained from hemolysate which contains still some compound(s) which can influence the shift of the Root effect toward higher pH."}
{"id": "PMID:13865", "title": "Hydroxylation of dehydroepiandrosterone in the eye lens.", "content": "Hydroxylation of the steroid hormone dehydroepiandrosterone in the calf lens is inhibited by carbon monoxide and stimulated by NADPH. The enzyme concerned was found to be membrane-bound. Although the enzyme resembles the liver mono-oxygenase system in these characteristics, the presence of cytochrome P-450 in the lens could not be proved by measuring a difference spectrum with carbon monoxide, probably because the concentration of the enzyme is too low. Preparations of purified lens fiber plasma membranes also hydroxylate dehydroepiandrosterone. This indicates that the fiber plasma membranes act as supports for enzyme complexes. In this respect they resemble cytoplasmic membranes and plasma membranes derived from other tissues. Cultured lens cell contain the hydroxylating enzyme, although its activity is dependent on the culture conditions used. It is striking that in lens fibers the enzyme which seems to convert dehydroepiandrosterone specifically occurs on the plasma membranes, whereas, for instance, in liver, hemoproteins localized on the endoplasmic reticulum, exert hydroxylation activity towards a variety of steroids. This suggests some regulatory role for dehydroepiandrosterone in lens growth and metabolism.", "contents": "Hydroxylation of dehydroepiandrosterone in the eye lens. Hydroxylation of the steroid hormone dehydroepiandrosterone in the calf lens is inhibited by carbon monoxide and stimulated by NADPH. The enzyme concerned was found to be membrane-bound. Although the enzyme resembles the liver mono-oxygenase system in these characteristics, the presence of cytochrome P-450 in the lens could not be proved by measuring a difference spectrum with carbon monoxide, probably because the concentration of the enzyme is too low. Preparations of purified lens fiber plasma membranes also hydroxylate dehydroepiandrosterone. This indicates that the fiber plasma membranes act as supports for enzyme complexes. In this respect they resemble cytoplasmic membranes and plasma membranes derived from other tissues. Cultured lens cell contain the hydroxylating enzyme, although its activity is dependent on the culture conditions used. It is striking that in lens fibers the enzyme which seems to convert dehydroepiandrosterone specifically occurs on the plasma membranes, whereas, for instance, in liver, hemoproteins localized on the endoplasmic reticulum, exert hydroxylation activity towards a variety of steroids. This suggests some regulatory role for dehydroepiandrosterone in lens growth and metabolism."}
{"id": "PMID:13866", "title": "Elevated erythrocyte glutathione associated with elevated substrate in high- and low-glutathione sheep.", "content": "Erythrocyte glutathione concentration increases dramatically in sheep when they become anemic. To determine the mechanism of this change in glutathione control, we measured the enzymes and substrates necessary for glutathione control, we measured the enzymes and substrates necessary for glutathione synthesis after acute blood loss in both low- (gamma-glutamylcysteine synthetase deficient) and high-glutathione sheep. Erythrocyte glutamate, ATP, and glycine increased dramatically in all sheep. Erythrocyte gamma-glutamylcysteine synthetase increased slowly and seemed unrelated to changes in glutathione. Erythrocyte glutathione synthetase and cysteine and plasma cysteine, glutamate and glycine did not change significantly. Apparently substrate concentrations may be important in regulating erythrocyte glutathione levels.", "contents": "Elevated erythrocyte glutathione associated with elevated substrate in high- and low-glutathione sheep. Erythrocyte glutathione concentration increases dramatically in sheep when they become anemic. To determine the mechanism of this change in glutathione control, we measured the enzymes and substrates necessary for glutathione control, we measured the enzymes and substrates necessary for glutathione synthesis after acute blood loss in both low- (gamma-glutamylcysteine synthetase deficient) and high-glutathione sheep. Erythrocyte glutamate, ATP, and glycine increased dramatically in all sheep. Erythrocyte gamma-glutamylcysteine synthetase increased slowly and seemed unrelated to changes in glutathione. Erythrocyte glutathione synthetase and cysteine and plasma cysteine, glutamate and glycine did not change significantly. Apparently substrate concentrations may be important in regulating erythrocyte glutathione levels."}
{"id": "PMID:13867", "title": "Inactivation of mitochondrial 2-oxoglutarate dehydrogenase complex as a result of phospholipid degradation induced by freeze-thawing.", "content": "The inactivation of 2-oxoglutarate dehydrogenase complex by freeze-thawing was examined along with alterations of membrane phospholipids, in order to elucidate the mechanism of freezing injury in mitochondria. The dehydrogenase complex activity in slowly frozen and thawed mitochondria decreased to 70% as compared to intact mitochondria and further decreased during incubation. This inactivation during incubation was temperature dependent, i.e., at temperatures up to 25 degrees C there was a slight decrease, while at higher temperatures there was a marked decrease in the dehydrogenase complex activity. Simultaneously, there was a significant accumulation of free fatty acids, generated from mitochondrial phospholipids, which inhibited 2-oxoglutarate dehydrogenase and subsequently enzyme complex activity. Oxoglutarate dehydrogenase activity in mitochondria was markedly inhibited by exogenous phospholipase A,  and this inhibition was partially prevented with bovine serum albumin. Furthermore, when intrinsic phospholipase A was either inhibited or stimulated, there was a respective decrease or increase in the enzyme complex inactivation. The activity of the purified enzyme complex decreased slightly after slow freezing, but remained constant even when incubated at temperatures up to 32 degrees C. However, the activity of this enzyme complex was markedly reduced when incubated either in the presence of venom phospholipase A or with exogenous fatty acid. The relationship between inactivation of the 2-oxoglutarate dehydrogenase complex, phospholipase A activation and production of free fatty acids in frozen and thawed mitochondria is discussed.", "contents": "Inactivation of mitochondrial 2-oxoglutarate dehydrogenase complex as a result of phospholipid degradation induced by freeze-thawing. The inactivation of 2-oxoglutarate dehydrogenase complex by freeze-thawing was examined along with alterations of membrane phospholipids, in order to elucidate the mechanism of freezing injury in mitochondria. The dehydrogenase complex activity in slowly frozen and thawed mitochondria decreased to 70% as compared to intact mitochondria and further decreased during incubation. This inactivation during incubation was temperature dependent, i.e., at temperatures up to 25 degrees C there was a slight decrease, while at higher temperatures there was a marked decrease in the dehydrogenase complex activity. Simultaneously, there was a significant accumulation of free fatty acids, generated from mitochondrial phospholipids, which inhibited 2-oxoglutarate dehydrogenase and subsequently enzyme complex activity. Oxoglutarate dehydrogenase activity in mitochondria was markedly inhibited by exogenous phospholipase A,  and this inhibition was partially prevented with bovine serum albumin. Furthermore, when intrinsic phospholipase A was either inhibited or stimulated, there was a respective decrease or increase in the enzyme complex inactivation. The activity of the purified enzyme complex decreased slightly after slow freezing, but remained constant even when incubated at temperatures up to 32 degrees C. However, the activity of this enzyme complex was markedly reduced when incubated either in the presence of venom phospholipase A or with exogenous fatty acid. The relationship between inactivation of the 2-oxoglutarate dehydrogenase complex, phospholipase A activation and production of free fatty acids in frozen and thawed mitochondria is discussed."}
{"id": "PMID:13868", "title": "Functional equivalence of iron bound to human transferrin at low pH or high pH.", "content": "Human transferrin was labeled with 59Fe at one of its two metal-binding sites (designated A) at pH 6.0. 55Fe was then added to site B at pH 7.5. Both isotopes of iron were taken up in equal proportions by human reticulocytes. These experiments do not support the hypothesis that each binding site of transferrin has a different physiologic function.", "contents": "Functional equivalence of iron bound to human transferrin at low pH or high pH. Human transferrin was labeled with 59Fe at one of its two metal-binding sites (designated A) at pH 6.0. 55Fe was then added to site B at pH 7.5. Both isotopes of iron were taken up in equal proportions by human reticulocytes. These experiments do not support the hypothesis that each binding site of transferrin has a different physiologic function."}
{"id": "PMID:13869", "title": "Studies on the mechanism of NADPH oxidation by the granule fraction isolated from human resting polymorphonuclear blood cells.", "content": "Various factor affecting NADPH-oxidation by resting human leucocyte granules (LG) at acid pH, have been investigated. It was found that: 1) oxidation of NADPH by LG was increasingly inhibited by increased cyanide concentrations in the medium and was abolished by 4 mM cyanide. 2) with or without cyanide in the incubation medium, LG omitted, Mn++ in the presence of NADPH induced superoxide anion (O- WITH 2) production, as evidenced by oxygen consumption and H2O2 production, which were abolished (in the absence of cyanide) by cytochrome C (a potent O- with 2 scavenger). 3) Both NADPH oxidation in the presence of 2 mM cyanide (cyanide-resistant) and in its absence (cyanide-sensitive) by LG occurred only in the presence of Mn++, and both were inhibited by superoxide dismutase. 4) Cyanide-resistant NADPH oxidation by LG generated H2O2, was inhibited by H2O2 and was not modified by \"active\" catalase. The ratio of cyanide-resistant NADPH oxidation/O2 uptake was 1 up to 1.25 mM NADPH, and increased above this concentration. 5) Cyanide-sensitive NADPH oxidation was inhibited by catalase and increased upon addition of H2O2. The ratio of cyanide-sensitive NADPH oxidation/O2 uptake was 2. It was concluded that after initiation by O - with 2, produced independently of LG, two sequential types of LG dependent NADPH oxidations occur. First, an O - with 2-dependent protein mediated NADPH oxidation (cyanide-resistant) which generates H2O2 and O - with 2 occurs. Second, NADPH peroxidation (cyanide-sensitive) which utilizes H2O2 takes place.", "contents": "Studies on the mechanism of NADPH oxidation by the granule fraction isolated from human resting polymorphonuclear blood cells. Various factor affecting NADPH-oxidation by resting human leucocyte granules (LG) at acid pH, have been investigated. It was found that: 1) oxidation of NADPH by LG was increasingly inhibited by increased cyanide concentrations in the medium and was abolished by 4 mM cyanide. 2) with or without cyanide in the incubation medium, LG omitted, Mn++ in the presence of NADPH induced superoxide anion (O- WITH 2) production, as evidenced by oxygen consumption and H2O2 production, which were abolished (in the absence of cyanide) by cytochrome C (a potent O- with 2 scavenger). 3) Both NADPH oxidation in the presence of 2 mM cyanide (cyanide-resistant) and in its absence (cyanide-sensitive) by LG occurred only in the presence of Mn++, and both were inhibited by superoxide dismutase. 4) Cyanide-resistant NADPH oxidation by LG generated H2O2, was inhibited by H2O2 and was not modified by \"active\" catalase. The ratio of cyanide-resistant NADPH oxidation/O2 uptake was 1 up to 1.25 mM NADPH, and increased above this concentration. 5) Cyanide-sensitive NADPH oxidation was inhibited by catalase and increased upon addition of H2O2. The ratio of cyanide-sensitive NADPH oxidation/O2 uptake was 2. It was concluded that after initiation by O - with 2, produced independently of LG, two sequential types of LG dependent NADPH oxidations occur. First, an O - with 2-dependent protein mediated NADPH oxidation (cyanide-resistant) which generates H2O2 and O - with 2 occurs. Second, NADPH peroxidation (cyanide-sensitive) which utilizes H2O2 takes place."}
{"id": "PMID:13870", "title": "Genetics and asexual reproduction of the sea anemone Metridium senile.", "content": "1. Metridium senile was studied for phosphohexose-isomerase variation at three locations on Cape Cod, Massachusetts: Woods Hole, Cape Cod Canal, and Barnstable Town Boat Harbor. 2. All three locations exhibited significant polymorphism for PHI. 3. Mapping of individual polyps was performed at Barnstable to analyze spatial distributions of clones and genotypes. 4. In Barnstable, PHI does not depart significantly from Hardy-Weinberg expectations at the time of establishment of new polyps, and establishment of larvae is spatially random with respect to PHI genotype. 5. Asexual reproduction was uses as a meausre of the relative success of different PHI genotypes. There are indications that not all genotypes are equally likely to produce large clones. 6. There is significant heterogeneity among the three locations with respect to PHI genotype frequencies, suggesting that there may be geographical differentiation of the populations. 7. Sessile, asexual organisms provide powerful tools for examining the dynamic aspects of genetic structure in natural populations.", "contents": "Genetics and asexual reproduction of the sea anemone Metridium senile. 1. Metridium senile was studied for phosphohexose-isomerase variation at three locations on Cape Cod, Massachusetts: Woods Hole, Cape Cod Canal, and Barnstable Town Boat Harbor. 2. All three locations exhibited significant polymorphism for PHI. 3. Mapping of individual polyps was performed at Barnstable to analyze spatial distributions of clones and genotypes. 4. In Barnstable, PHI does not depart significantly from Hardy-Weinberg expectations at the time of establishment of new polyps, and establishment of larvae is spatially random with respect to PHI genotype. 5. Asexual reproduction was uses as a meausre of the relative success of different PHI genotypes. There are indications that not all genotypes are equally likely to produce large clones. 6. There is significant heterogeneity among the three locations with respect to PHI genotype frequencies, suggesting that there may be geographical differentiation of the populations. 7. Sessile, asexual organisms provide powerful tools for examining the dynamic aspects of genetic structure in natural populations."}
{"id": "PMID:13871", "title": "Activity and physiological significance of the pleopods in the respiration of Callianassa californiensis (Dana) (Crustacea: Thalassinidea).", "content": "1. The pleopods of C. californiensis, a potential site for extrabranchial oxygen exchange, do not contribute significantly to oxygen consumption. 2. C. californiensis has a gill surface area of 4.13 +/- 0.72 cm2/g wet body weight, the lowest value yet reported for a totally aquatic crustacean. 3. C. californiensis, when placed in simulated burrow conditions, regulates the PO2 very loosely in its immediate microhabitat, using its pleopods. 4. Field studies of pH and PO2 values in burrows of C. californiensis indicate that animal movement may play a large part in water exchange between the surface and burrow. 5. Activity studies suggest that oxygen is not critical to C. californiensis on a short term basis. Perception of oxygen after long deprivation may signal the possibility of renewed feeding and activity at the surface of its burrow.", "contents": "Activity and physiological significance of the pleopods in the respiration of Callianassa californiensis (Dana) (Crustacea: Thalassinidea). 1. The pleopods of C. californiensis, a potential site for extrabranchial oxygen exchange, do not contribute significantly to oxygen consumption. 2. C. californiensis has a gill surface area of 4.13 +/- 0.72 cm2/g wet body weight, the lowest value yet reported for a totally aquatic crustacean. 3. C. californiensis, when placed in simulated burrow conditions, regulates the PO2 very loosely in its immediate microhabitat, using its pleopods. 4. Field studies of pH and PO2 values in burrows of C. californiensis indicate that animal movement may play a large part in water exchange between the surface and burrow. 5. Activity studies suggest that oxygen is not critical to C. californiensis on a short term basis. Perception of oxygen after long deprivation may signal the possibility of renewed feeding and activity at the surface of its burrow."}
{"id": "PMID:13872", "title": "Intracellular crystal-bearing vesicles in the epidermis of scleractinian corals, Astrangia danae (Agassiz) and Porites porites (Pallas).", "content": "Orthorhombic aragonitic crystals, embedded with a granular lipo-protein matrix and surrounded by a trilaminar membrane, are localized in the apical cytoplasm of epidermal cells of Scleractinian corals. Adult specimens of Astrangia danae (Agassiz) and settled planulae of Porites porites (Pallas) contain crystals averaging 0.7 mu by 0.1 mu by 0.3 mu within Golgi-derived vesicles. Short-term labelling with 45Ca reveals distribution of radioactivity amont a basic tissue fraction (92%) an acid tissue fraction (5%) and a skeletal fraction (3%). Identification of the primordial crystal population within membrane-bound visicles provides overwhelming evidence for the intracellular mode of calcification in Scleractinia. Moreover, it permits development of a novel concept of cellular regulation over these dynamic events. The membrane-bound vesicel is a miniature crystal fabrication station and a vehicle responsible for transportation of seed crystals and an organic matrix material to sites of discharge from the cell. The vesicle membrane becomes a probable locus of active transport and enzymatic activity as well as a physical barrier to be penetrated for release of vesicle contents into the extracellular milieu. Contact between the vesicle membrane and the plasmalemma would result in exocytosis and the onset of skeletogenesis. Principles governing crystal growth would prevail from then on. The released crystal becomes a nucleation catalyst and the organic matrix, a supply of ionic calcium for self-limiting crystallization. Crystals are produced by the organism spontaneously and continuously from shortly after larval attachment throughout the life of the polyp. Therefore, these membrane-bound vesicles signal the dynamic process by which initiation, differentiation, growth and limitation of the coral skeleton is regulated.", "contents": "Intracellular crystal-bearing vesicles in the epidermis of scleractinian corals, Astrangia danae (Agassiz) and Porites porites (Pallas). Orthorhombic aragonitic crystals, embedded with a granular lipo-protein matrix and surrounded by a trilaminar membrane, are localized in the apical cytoplasm of epidermal cells of Scleractinian corals. Adult specimens of Astrangia danae (Agassiz) and settled planulae of Porites porites (Pallas) contain crystals averaging 0.7 mu by 0.1 mu by 0.3 mu within Golgi-derived vesicles. Short-term labelling with 45Ca reveals distribution of radioactivity amont a basic tissue fraction (92%) an acid tissue fraction (5%) and a skeletal fraction (3%). Identification of the primordial crystal population within membrane-bound visicles provides overwhelming evidence for the intracellular mode of calcification in Scleractinia. Moreover, it permits development of a novel concept of cellular regulation over these dynamic events. The membrane-bound vesicel is a miniature crystal fabrication station and a vehicle responsible for transportation of seed crystals and an organic matrix material to sites of discharge from the cell. The vesicle membrane becomes a probable locus of active transport and enzymatic activity as well as a physical barrier to be penetrated for release of vesicle contents into the extracellular milieu. Contact between the vesicle membrane and the plasmalemma would result in exocytosis and the onset of skeletogenesis. Principles governing crystal growth would prevail from then on. The released crystal becomes a nucleation catalyst and the organic matrix, a supply of ionic calcium for self-limiting crystallization. Crystals are produced by the organism spontaneously and continuously from shortly after larval attachment throughout the life of the polyp. Therefore, these membrane-bound vesicles signal the dynamic process by which initiation, differentiation, growth and limitation of the coral skeleton is regulated."}
{"id": "PMID:13873", "title": "Psychopathy and arousal: a new interpretation of the psychophysiological literature.", "content": "The psychophysiological literature on psychopathy is reviewed in the context of low-arousal theory. Difficulties in the theory are discussed both in general terms and specifically in relation to psychopathy. Contrary to the low-arousal theory, the data indicate that psychopaths exhibit a wider degree of variability in arousal levels and reactivity than normal indiciduals. A more accurate model of the disorder might be one in which psychopaths display a faster rate and a greater magnitude of change in physiological and behavioral activity than normals. It is suggested that psychopathy might be usefully viewed as a biochemical disturbance manifested in abnormal oscillations in neurotransmitter functioning, autonomic activity, and behavior. The literature is reexamined in light of this hypothesis, and a number of avenues for further research are discussed.", "contents": "Psychopathy and arousal: a new interpretation of the psychophysiological literature. The psychophysiological literature on psychopathy is reviewed in the context of low-arousal theory. Difficulties in the theory are discussed both in general terms and specifically in relation to psychopathy. Contrary to the low-arousal theory, the data indicate that psychopaths exhibit a wider degree of variability in arousal levels and reactivity than normal indiciduals. A more accurate model of the disorder might be one in which psychopaths display a faster rate and a greater magnitude of change in physiological and behavioral activity than normals. It is suggested that psychopathy might be usefully viewed as a biochemical disturbance manifested in abnormal oscillations in neurotransmitter functioning, autonomic activity, and behavior. The literature is reexamined in light of this hypothesis, and a number of avenues for further research are discussed."}
{"id": "PMID:13874", "title": "HNMR of succinate binding to aspartate transcarbamylase. A comparison of results in D2O and H2O.", "content": "The interaction of succinate with asparatete transcarbamylase from Escherichia coli has been studied by magnetic resonance relaxation measurements of the dicarboxylic acid methylene protons in H2O solutions. The pH  and temperature dependence of the relaxation in the presence of either native asparte transcarbamylase or its catalytic subunit in H2O solutions is qualitatively very similar to the corresponding situation utilizing D2O  as the solvent. From previous result of measurements in D2O[C.B. Beard and P.G. Schmidt, Biochemistry 12(1973)2255] a mechanism was proposed involving 2 protonated groups affecting succinate binding and titratable over the pH range 7-10. Quantitatively, fitting the data from H2O solutions to the mechanism yeilds values of the fitting parameters generally in good agreement with the D2O experiments. The main exceptions are the pKa values calculated for the two titratable groups. For these species the values obtained in the presence of the catalytic subunit are 6.7 and 7.8 in H2O solutions versus 7.3 and 8.6 in D2O solutions. In the presence of native enzyme the corresponding values are 6.8 and 8.3 in H2O versus 7.6 and 9.2 in D2O. These observed differences are consistent with differences in ionization constants of weak acids in D2O relative to H2O. The results imply that succinate interaction with the enzyme active site is similar in the two solvents.", "contents": "HNMR of succinate binding to aspartate transcarbamylase. A comparison of results in D2O and H2O. The interaction of succinate with asparatete transcarbamylase from Escherichia coli has been studied by magnetic resonance relaxation measurements of the dicarboxylic acid methylene protons in H2O solutions. The pH  and temperature dependence of the relaxation in the presence of either native asparte transcarbamylase or its catalytic subunit in H2O solutions is qualitatively very similar to the corresponding situation utilizing D2O  as the solvent. From previous result of measurements in D2O[C.B. Beard and P.G. Schmidt, Biochemistry 12(1973)2255] a mechanism was proposed involving 2 protonated groups affecting succinate binding and titratable over the pH range 7-10. Quantitatively, fitting the data from H2O solutions to the mechanism yeilds values of the fitting parameters generally in good agreement with the D2O experiments. The main exceptions are the pKa values calculated for the two titratable groups. For these species the values obtained in the presence of the catalytic subunit are 6.7 and 7.8 in H2O solutions versus 7.3 and 8.6 in D2O solutions. In the presence of native enzyme the corresponding values are 6.8 and 8.3 in H2O versus 7.6 and 9.2 in D2O. These observed differences are consistent with differences in ionization constants of weak acids in D2O relative to H2O. The results imply that succinate interaction with the enzyme active site is similar in the two solvents."}
{"id": "PMID:13875", "title": "The subunit structure of the hemocyanin from the crayfish Jasus edwardsii.", "content": "The hemocyanin from the crayfish Jasus edwardsii(=lalandii) has been studied using ultracentrifugation, viscosity, circular dichroism and oxygen binding techniques. Sedimentation velocity experiments at pH 7.0 indicated the presence of principal species with S 20w=16.4 S, and at higher pH the presence of a species with S20,w=5.2S. Sedimentation equilibrium experiments yielded molecular weights of 490 000 and 81 000 respectively, indicating that the larger unit is a hexamer of the monomer unit. However, preliminary experiments with gel filtration and electrophoresis under denaturing conditions indicate that more than one monomer species may be present with molecular weight in the range 76-100 000. Circular dichroism (CD) spectra are presented at pH 7.0,8.6,10.0 and 11.0 for oxy-, deoxy- and apo-hemocyanins. Slight differences were observed in the magnitude of the bands in the presence or absence of Mg++. Oxygen binding studies have been made at pH 6.1,7.0,8.8 and 10.6, in the presence of 0.01 M MgCl2. The extent of cooperative binding was indicated by a maximum value of n=3.7, and a pronounced bohr effect was observed.", "contents": "The subunit structure of the hemocyanin from the crayfish Jasus edwardsii. The hemocyanin from the crayfish Jasus edwardsii(=lalandii) has been studied using ultracentrifugation, viscosity, circular dichroism and oxygen binding techniques. Sedimentation velocity experiments at pH 7.0 indicated the presence of principal species with S 20w=16.4 S, and at higher pH the presence of a species with S20,w=5.2S. Sedimentation equilibrium experiments yielded molecular weights of 490 000 and 81 000 respectively, indicating that the larger unit is a hexamer of the monomer unit. However, preliminary experiments with gel filtration and electrophoresis under denaturing conditions indicate that more than one monomer species may be present with molecular weight in the range 76-100 000. Circular dichroism (CD) spectra are presented at pH 7.0,8.6,10.0 and 11.0 for oxy-, deoxy- and apo-hemocyanins. Slight differences were observed in the magnitude of the bands in the presence or absence of Mg++. Oxygen binding studies have been made at pH 6.1,7.0,8.8 and 10.6, in the presence of 0.01 M MgCl2. The extent of cooperative binding was indicated by a maximum value of n=3.7, and a pronounced bohr effect was observed."}
{"id": "PMID:13876", "title": "The molecular dynamics of hyaluronates in solution.", "content": "The dynamic properties of hyaluronate solutions are discussed with relevance to some problems in sensory physiology (mechanoelectrical transduction), renal physiology, interstitial fluid regulation, and especially to the causes of open-angle glaucoma. With respect to the last problem: as recent biochemical evidence indicates that the hyaloid membrane does not exist, it now seems worthwhile to consider the increase in intraocular pressure present in the eye with glaucoma to be due--at least in the open-angle case--to a change in the specific gravity and hydrophilic nature of the hyaluronic acid in the vitreous body in particular, as well as in the trabecular meshwork. Densimetric experimental evidence indicates that the hyaluronate system could, indeed, produce the pressure changes seen in glaucoma, if intraocular pH changed but slightly. A hypothesis concerning the effect of acetazol amide on intraocular pressure is also presented.", "contents": "The molecular dynamics of hyaluronates in solution. The dynamic properties of hyaluronate solutions are discussed with relevance to some problems in sensory physiology (mechanoelectrical transduction), renal physiology, interstitial fluid regulation, and especially to the causes of open-angle glaucoma. With respect to the last problem: as recent biochemical evidence indicates that the hyaloid membrane does not exist, it now seems worthwhile to consider the increase in intraocular pressure present in the eye with glaucoma to be due--at least in the open-angle case--to a change in the specific gravity and hydrophilic nature of the hyaluronic acid in the vitreous body in particular, as well as in the trabecular meshwork. Densimetric experimental evidence indicates that the hyaluronate system could, indeed, produce the pressure changes seen in glaucoma, if intraocular pH changed but slightly. A hypothesis concerning the effect of acetazol amide on intraocular pressure is also presented."}
{"id": "PMID:13877", "title": "[Acid-base balance of spinal cord fluid in the post-resuscitation period].", "content": "Experiments were conducted on dogs which had sustained a 10-minute circulatory arrest caused by electrotrauma; the acid-base balance of the cerebrospinal fluid (CSF) and the blood was studied during the postreanimation period. Although the systemic uncompensated acidosis persisted in the course of the first hour of the postreanimation period, compensation of the CSF acidosis occurred much earlier and the pH was maintained at the initial level for 6 hours. Despite a high lactate concentration for a period of 3 hours of the postreanimation period the bicarbonate concentration remained near the initial one at this period.", "contents": "[Acid-base balance of spinal cord fluid in the post-resuscitation period]. Experiments were conducted on dogs which had sustained a 10-minute circulatory arrest caused by electrotrauma; the acid-base balance of the cerebrospinal fluid (CSF) and the blood was studied during the postreanimation period. Although the systemic uncompensated acidosis persisted in the course of the first hour of the postreanimation period, compensation of the CSF acidosis occurred much earlier and the pH was maintained at the initial level for 6 hours. Despite a high lactate concentration for a period of 3 hours of the postreanimation period the bicarbonate concentration remained near the initial one at this period."}
{"id": "PMID:13878", "title": "[Effect of hypoxia on the concentration of nicotinamide coenzymes in the tissues of newborn rats].", "content": "The content of nicotinamide coenzymes (NAD, NAD-H, NADP, NADP-H) was studied in the brain, heart and liver tissue of the newborn rats kept in hypoxic gaseous medium with a 4% oxygen content for 2 1/2 hours. There was a marked reduction of NAD content, an accumulation of NAD-H and a more than two-fold fall of the NAD/NAD-H ratio particularly marked in the brain and heart. A reduction of the NADP-H values chiefly in the liver and of the general pool of NAD-phosphates in the tissues of the newborn rats under study occurred under the same conditions. The data obtained led to the conclusion that oxygen deficiency had a significant influence on the concentration and the ratio of the nicotinamide coenzymes in the tissues of newborn rats, that in its turn led to the changes in the level and the direction of the redox processes under the conditions of hypoxia.", "contents": "[Effect of hypoxia on the concentration of nicotinamide coenzymes in the tissues of newborn rats]. The content of nicotinamide coenzymes (NAD, NAD-H, NADP, NADP-H) was studied in the brain, heart and liver tissue of the newborn rats kept in hypoxic gaseous medium with a 4% oxygen content for 2 1/2 hours. There was a marked reduction of NAD content, an accumulation of NAD-H and a more than two-fold fall of the NAD/NAD-H ratio particularly marked in the brain and heart. A reduction of the NADP-H values chiefly in the liver and of the general pool of NAD-phosphates in the tissues of the newborn rats under study occurred under the same conditions. The data obtained led to the conclusion that oxygen deficiency had a significant influence on the concentration and the ratio of the nicotinamide coenzymes in the tissues of newborn rats, that in its turn led to the changes in the level and the direction of the redox processes under the conditions of hypoxia."}
{"id": "PMID:13879", "title": "Effect of cyanide on NADPH oxidation by granules from human polymorphonuclear leukocytes.", "content": "Cyanide has been shown to stimulate both oxygen uptake and hexose monophosphate shunt activity in phagocytizing human polymorphonuclear leukocytes. It also stimulates the oxidation of NADPH by a particulate fraction derived from phagocytizing cells. This stimulation of NADPH oxidase is not observed in the presence of exogenous Mn2+. Studies with purified enzymes have shown that CN- also stimulates NADPH oxidation by horseradish peroxidase or lactoperoxidase, suggesting that the respiratory burst might be initiated by activation of a peroxidase-like enzyme in the human polymorphonuclear leukocyte. Based on studies of others, however, it does not appear as though the enzyme is identical to myeloperoxidase. The mechanism of the CN- stimulation appears to involve an oxidatic chain reaction, since it stimulates markedly NADPH oxidation in the presence of an artificial superoxide-generating system.", "contents": "Effect of cyanide on NADPH oxidation by granules from human polymorphonuclear leukocytes. Cyanide has been shown to stimulate both oxygen uptake and hexose monophosphate shunt activity in phagocytizing human polymorphonuclear leukocytes. It also stimulates the oxidation of NADPH by a particulate fraction derived from phagocytizing cells. This stimulation of NADPH oxidase is not observed in the presence of exogenous Mn2+. Studies with purified enzymes have shown that CN- also stimulates NADPH oxidation by horseradish peroxidase or lactoperoxidase, suggesting that the respiratory burst might be initiated by activation of a peroxidase-like enzyme in the human polymorphonuclear leukocyte. Based on studies of others, however, it does not appear as though the enzyme is identical to myeloperoxidase. The mechanism of the CN- stimulation appears to involve an oxidatic chain reaction, since it stimulates markedly NADPH oxidation in the presence of an artificial superoxide-generating system."}
{"id": "PMID:13884", "title": "Oxygen affinity of haemoglobin and red cell acid-base status in patients with severe chronic obstructive lung disease.", "content": "The oxygen affinity of hemoglobin and the factors determining the position of the oxygen dissociation curve were investigated in twenty-five patients with severe chronic obstructive lung disease. Patients have been separated into three groups: group I showed a normal or mild decrease of PaO2, group II a moderate fall in arterial oxygen pressure, and group III a severe hypoxia with balanced acid-base equilibrium and hypercapnia. Blood hemoglobin exhibited a significant increase in all groups, indicating an improved oxygen transport. In most patients a leftward shifting of the oxygen dissociation curve occurred. It is discussed that the tendency to left shifting is based upon alkalosis inside the red cells, evidently demonstrated in all groups studied. 2,3-diphosphoglycerate showed no close relation to evaluated oxygen affinity of hemoglobin. The evidence for an increased oxygen affinity may reveal a further compensatory mechanism in oxygen transport in patients with pulmonary disorders. Additionally the alkalosis inside the cells may counterbalance too great a right shifting of oxygen dissociation curve in vivo when severe hypoxia and hypercapnia occur.", "contents": "Oxygen affinity of haemoglobin and red cell acid-base status in patients with severe chronic obstructive lung disease. The oxygen affinity of hemoglobin and the factors determining the position of the oxygen dissociation curve were investigated in twenty-five patients with severe chronic obstructive lung disease. Patients have been separated into three groups: group I showed a normal or mild decrease of PaO2, group II a moderate fall in arterial oxygen pressure, and group III a severe hypoxia with balanced acid-base equilibrium and hypercapnia. Blood hemoglobin exhibited a significant increase in all groups, indicating an improved oxygen transport. In most patients a leftward shifting of the oxygen dissociation curve occurred. It is discussed that the tendency to left shifting is based upon alkalosis inside the red cells, evidently demonstrated in all groups studied. 2,3-diphosphoglycerate showed no close relation to evaluated oxygen affinity of hemoglobin. The evidence for an increased oxygen affinity may reveal a further compensatory mechanism in oxygen transport in patients with pulmonary disorders. Additionally the alkalosis inside the cells may counterbalance too great a right shifting of oxygen dissociation curve in vivo when severe hypoxia and hypercapnia occur."}
{"id": "PMID:13888", "title": "Hypercapnia and resultant bicarbonate transfer processes in an elasmobranch fish (Scyliorhinus stellaris).", "content": "In order to test the effects of hypercapnia on the acid-base status of fish, larger spotted dogfish were exposed to sudden changes of PCO2 in a closed seawater recirculation system. pH, PCO2 and PO2 were determined in arterial blood and seawater. The exchange of bicarbonate between extracellular space (ECS), intracellular space (ICS), and seawater (SW) was obtained from changes of the total bicarbonate amount in ECS and SW. After fourfold increase of PCO2 arterial pH fell markedly, but started to recover immediately towards control values. This was caused by compensatory accumulation of bicarbonate in the ECS. According to the origin of the extracellular bicarbonate increase three periods could be distinguished: 1.-- Bicarbonate transferred from ICS to both ECS and SW; 2. -- Bicarbonate transferred from both SW and ICS to ECS; 3. -- Bicarbonate transferred from SW to both ECS and ICS. After return to normocapnia similar periods occurred with opposite transfer directions and delayed period transitions. In the first period the ICS was found to be the only source for compensatory bicarbonate increases and even in the second period the ICS contributed to compensation of the extracellular pH. Thus bicarbonate exchange with the ICS appears to be an important regulatory mechanism diminishing the extracellular pH variations after changes in PCO2, before other compensatory mechanisms are initiated.", "contents": "Hypercapnia and resultant bicarbonate transfer processes in an elasmobranch fish (Scyliorhinus stellaris). In order to test the effects of hypercapnia on the acid-base status of fish, larger spotted dogfish were exposed to sudden changes of PCO2 in a closed seawater recirculation system. pH, PCO2 and PO2 were determined in arterial blood and seawater. The exchange of bicarbonate between extracellular space (ECS), intracellular space (ICS), and seawater (SW) was obtained from changes of the total bicarbonate amount in ECS and SW. After fourfold increase of PCO2 arterial pH fell markedly, but started to recover immediately towards control values. This was caused by compensatory accumulation of bicarbonate in the ECS. According to the origin of the extracellular bicarbonate increase three periods could be distinguished: 1.-- Bicarbonate transferred from ICS to both ECS and SW; 2. -- Bicarbonate transferred from both SW and ICS to ECS; 3. -- Bicarbonate transferred from SW to both ECS and ICS. After return to normocapnia similar periods occurred with opposite transfer directions and delayed period transitions. In the first period the ICS was found to be the only source for compensatory bicarbonate increases and even in the second period the ICS contributed to compensation of the extracellular pH. Thus bicarbonate exchange with the ICS appears to be an important regulatory mechanism diminishing the extracellular pH variations after changes in PCO2, before other compensatory mechanisms are initiated."}
{"id": "PMID:13889", "title": "[Kinetics of the compensation of respiratory acidosis induced by experimental chronic hypercapnia in man (author's transl)].", "content": "Four groups of male volunteers have been exposed in a tight climatical chamber to PICO2 of 14, 21, 28 and 32 torr; exposure periods varied from two to 30 days, between two reference periods in normal air. The results deal with the evolution of arterial blood acid-base equilibrium and that of renal response in relation to PICO2. In all exposures, the carbon dioxide alveolar overload increases by several torr during the first 24 hours on account of attenuation of the initial hyperventilation. Kinetics of the respiratory acidosis compensation differs according to hypercapnia which is moderate (PICO2 of 14 and 21 torr) or relatively severe (PICO2 of 28 and 32 torr). The decrease in arterial pH lessens as early as the 24th hour at PICO2 28 and 32 torr, and only after two days at PICO2 14 and 21 torr. The renal response is characterized by a significant increase in aciduria during the first 24 hours at PICO2 28 and 32 torr; the changes are smaller and start latter at PICO2 14 torr.", "contents": "[Kinetics of the compensation of respiratory acidosis induced by experimental chronic hypercapnia in man (author's transl)]. Four groups of male volunteers have been exposed in a tight climatical chamber to PICO2 of 14, 21, 28 and 32 torr; exposure periods varied from two to 30 days, between two reference periods in normal air. The results deal with the evolution of arterial blood acid-base equilibrium and that of renal response in relation to PICO2. In all exposures, the carbon dioxide alveolar overload increases by several torr during the first 24 hours on account of attenuation of the initial hyperventilation. Kinetics of the respiratory acidosis compensation differs according to hypercapnia which is moderate (PICO2 of 14 and 21 torr) or relatively severe (PICO2 of 28 and 32 torr). The decrease in arterial pH lessens as early as the 24th hour at PICO2 28 and 32 torr, and only after two days at PICO2 14 and 21 torr. The renal response is characterized by a significant increase in aciduria during the first 24 hours at PICO2 28 and 32 torr; the changes are smaller and start latter at PICO2 14 torr."}
{"id": "PMID:13892", "title": "[Respiratory function in patients with sickle cell disease (author's transl)].", "content": "Respiratory function was systematically studied in 61 patients with sickle cell disease, in and out of crisis. Pulmonary volumes and flows, blood gases and P50 were measured. It was found that : 1. vital capacity was decreased in about half of the patients (obstructive symptoms in five cases), 2. hypoxaemia existed under air, with a fall in hemoglobin saturation, 3. hypoxaemia existed under pure O2 showing the existence of veno-arterial shunts, 4. an increase in P50 revealed a decrease in haemoglobin oxygen affinity (P50 (7.40, 37 degrees C) torr = 49.08 -- 1.57 [Hb] (g/100 ml) +/- 4.81), 5. during sickle cell crisis, there was evidence of obstructive symptoms associated with a Pao2 decrease and a moderate alveolar hypoventilation. Several hypotheses concerning the restrictive syndrome and the hypoxaemia are discussed.", "contents": "[Respiratory function in patients with sickle cell disease (author's transl)]. Respiratory function was systematically studied in 61 patients with sickle cell disease, in and out of crisis. Pulmonary volumes and flows, blood gases and P50 were measured. It was found that : 1. vital capacity was decreased in about half of the patients (obstructive symptoms in five cases), 2. hypoxaemia existed under air, with a fall in hemoglobin saturation, 3. hypoxaemia existed under pure O2 showing the existence of veno-arterial shunts, 4. an increase in P50 revealed a decrease in haemoglobin oxygen affinity (P50 (7.40, 37 degrees C) torr = 49.08 -- 1.57 [Hb] (g/100 ml) +/- 4.81), 5. during sickle cell crisis, there was evidence of obstructive symptoms associated with a Pao2 decrease and a moderate alveolar hypoventilation. Several hypotheses concerning the restrictive syndrome and the hypoxaemia are discussed."}
{"id": "PMID:13893", "title": "Influence of oxygen and carbon dioxide on the plasma-erythrocyte pH relationship in normal human whole blood.", "content": "The influence of oxygenation level (oxyhaemoglobin saturation 0 or 100%) on the relationship between plasma pH and erythrocyte pH was studied, in vitro, in normal human blood submitted to changes in carbon dioxide tension. Firstly, the pH of both true and separated erythrolysates were compared: for the former, tonometry was carried out on whole blood, before red cells lysis; for the latter, equilibration was performed on erythrolysate, pH values appeared different: at PCO2 congruent to 21 and 38 Torr, separated erythrolysate was more alkaline than true one, and at PCO2 congruent to 0 it was more acid. Therefore, to estimate pHe-pHi relationship, pHi was evaluated on true erythrolysate. When haemoglobin passed from the reduced to the completely oxygenated state, a significant decrease of both pHe and pHi was observed for a given PCO2 (respectively about 0.05 and 0.08 pH unit), and of pHi for a given pHe (about 0.04 pH unit). In either extra or intraerythrocyte fluid, the oxygen-linked pH difference was  negatively correlated to PCO2.", "contents": "Influence of oxygen and carbon dioxide on the plasma-erythrocyte pH relationship in normal human whole blood. The influence of oxygenation level (oxyhaemoglobin saturation 0 or 100%) on the relationship between plasma pH and erythrocyte pH was studied, in vitro, in normal human blood submitted to changes in carbon dioxide tension. Firstly, the pH of both true and separated erythrolysates were compared: for the former, tonometry was carried out on whole blood, before red cells lysis; for the latter, equilibration was performed on erythrolysate, pH values appeared different: at PCO2 congruent to 21 and 38 Torr, separated erythrolysate was more alkaline than true one, and at PCO2 congruent to 0 it was more acid. Therefore, to estimate pHe-pHi relationship, pHi was evaluated on true erythrolysate. When haemoglobin passed from the reduced to the completely oxygenated state, a significant decrease of both pHe and pHi was observed for a given PCO2 (respectively about 0.05 and 0.08 pH unit), and of pHi for a given pHe (about 0.04 pH unit). In either extra or intraerythrocyte fluid, the oxygen-linked pH difference was  negatively correlated to PCO2."}
{"id": "PMID:13895", "title": "Carbuterol, fenoterol, orciprenaline, salbutamol and terbutaline per os in reversible obstructive chronic bronchitis.", "content": "The effects of tablets of carbuterol, orciprenaline, salbutemol, terbutaline and fenoterol at two dosages were studied using FEV1 and specific airway conductance as parameters. A placebo was used as a reference. Carbuterol and fenoterol proved to be more potent than the other sympathomimetic competitors. Fenoterol 5 mg was on the average somewhat less potent than 3 mg carbuterol. This differnce was not statistically significant for FEV1; it was significant three hours after intake for airway conductance. None of the drugs produced significant changes of the blood pressure. Carbuterol and 12 mg fenoterol caused a statistically significant increase in heart rate. ECG changes were observed in eight patients with the different beta-sympathomimetics, with the exception of 5 mg fenoterol.", "contents": "Carbuterol, fenoterol, orciprenaline, salbutamol and terbutaline per os in reversible obstructive chronic bronchitis. The effects of tablets of carbuterol, orciprenaline, salbutemol, terbutaline and fenoterol at two dosages were studied using FEV1 and specific airway conductance as parameters. A placebo was used as a reference. Carbuterol and fenoterol proved to be more potent than the other sympathomimetic competitors. Fenoterol 5 mg was on the average somewhat less potent than 3 mg carbuterol. This differnce was not statistically significant for FEV1; it was significant three hours after intake for airway conductance. None of the drugs produced significant changes of the blood pressure. Carbuterol and 12 mg fenoterol caused a statistically significant increase in heart rate. ECG changes were observed in eight patients with the different beta-sympathomimetics, with the exception of 5 mg fenoterol."}
{"id": "PMID:13899", "title": "Differentiation of metabolic adrenoceptors.", "content": "1 Cardiovascular and metabolic responses to intravenous infusion of isoprenaline were measured in fasted, anaesthetized cats. 2 Isoprenaline (0.2 mug kg-1 min-1 for 15 min) decreased diastolic blood pressure and increased heart rate, blood glucose, blood lactate and plasma free fatty acids. 3 Oxprenolol (0.5 mg/kg) antagonized all cardiovascular and metabolic effects of isoprenaline non-selectively. 4 Para-oxprenolol (0.25 mg/kg) and practolol (4 mg/kg) antagonized the effects of isoprenaline on heart rate and free fatty acids selectively. 5 H 35/25 ((I-(4-methylphenyl)-2-isopropyl aminopropanol) hydrochloride, 3 mg/kg) antagonized the effects of isoprenaline on blood pressure, glucose and lactate selectively. 6 It is concluded that metabolic adrenoceptors are differentiated into subtypes similar to those mediating cardiostimulation and vasodilatation.", "contents": "Differentiation of metabolic adrenoceptors. 1 Cardiovascular and metabolic responses to intravenous infusion of isoprenaline were measured in fasted, anaesthetized cats. 2 Isoprenaline (0.2 mug kg-1 min-1 for 15 min) decreased diastolic blood pressure and increased heart rate, blood glucose, blood lactate and plasma free fatty acids. 3 Oxprenolol (0.5 mg/kg) antagonized all cardiovascular and metabolic effects of isoprenaline non-selectively. 4 Para-oxprenolol (0.25 mg/kg) and practolol (4 mg/kg) antagonized the effects of isoprenaline on heart rate and free fatty acids selectively. 5 H 35/25 ((I-(4-methylphenyl)-2-isopropyl aminopropanol) hydrochloride, 3 mg/kg) antagonized the effects of isoprenaline on blood pressure, glucose and lactate selectively. 6 It is concluded that metabolic adrenoceptors are differentiated into subtypes similar to those mediating cardiostimulation and vasodilatation."}
{"id": "PMID:13900", "title": "Interactions between the effects of alpha- and beta-adrenoceptor agonists and adenine nucleotides on the membrane potential of cells in guinea-pig liver slices.", "content": "1 The beta-adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea-pig liver slices, in contrast to the large hyperpolarizations seen with alpha-agonists. However, after a selective alpha-adrenoceptor agonist has been applied, the response to isoprenaline becomes greatly enhanced. 2 Simultaneous application of small doses of an alpha- and beta-agonist produce hyperpolarizations larger than the sum of the responses to each agent alone. 3 These interactions occur with a range of sympathomimetic amines, including some which are not substrates for various processes for the uptake and inactivation of catecholamines. 4 Hyperpolarizations caused by externally applied cyclic adenosine-3',5'-monophosphate (cyclic AMP) also become larger after application of an alpha-agonist. 5 The adenine nucleotides adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP) hyperpolarize guinea-pig liver cells in the dose range 0.1-1.0 mM. This response is not increased after an alpha-agonist. However, ADP and ATP are themselves able to enhance the response to beta-agonists. 6 These interactions between alpha-agonists, beta-agonists and adenine nucleotides seem to involve steps subsequent to receptor activation. Changes in the intracellular actions of cyclic AMP may be concerned.", "contents": "Interactions between the effects of alpha- and beta-adrenoceptor agonists and adenine nucleotides on the membrane potential of cells in guinea-pig liver slices. 1 The beta-adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea-pig liver slices, in contrast to the large hyperpolarizations seen with alpha-agonists. However, after a selective alpha-adrenoceptor agonist has been applied, the response to isoprenaline becomes greatly enhanced. 2 Simultaneous application of small doses of an alpha- and beta-agonist produce hyperpolarizations larger than the sum of the responses to each agent alone. 3 These interactions occur with a range of sympathomimetic amines, including some which are not substrates for various processes for the uptake and inactivation of catecholamines. 4 Hyperpolarizations caused by externally applied cyclic adenosine-3',5'-monophosphate (cyclic AMP) also become larger after application of an alpha-agonist. 5 The adenine nucleotides adenosine 5'-diphosphate (ADP) and adenosine 5'-triphosphate (ATP) hyperpolarize guinea-pig liver cells in the dose range 0.1-1.0 mM. This response is not increased after an alpha-agonist. However, ADP and ATP are themselves able to enhance the response to beta-agonists. 6 These interactions between alpha-agonists, beta-agonists and adenine nucleotides seem to involve steps subsequent to receptor activation. Changes in the intracellular actions of cyclic AMP may be concerned."}
{"id": "PMID:13901", "title": "The beta-adrenoceptor of the human lymphocyte and human lung parenchyma.", "content": "1 The response of the beta-adrenoceptors of human lymphocytes to selective agonists and antagonists has been studied quantitatively by measuring changes in cyclic adenosine-3',5'-monophosphate (cyclic AMP) levels. 2 The receptor was activated by isoprenaline and by salbutamol, and blocked by propranolol but not by practolol. A similar pattern of response was obtained with fragments of human lung tissue. 3 The mean value for pA2 for propranolol was 8.34 and for practolol was 3.95. 4 These findings indicate that the lymphocyte beta-adrenoceptor is a beta2-receptor and support the solidity of using lymphocytes to study beta-adrenoceptor function in bronchial asthma. It may also be of use in the evaluation of selective beta2-blocking drugs in man.", "contents": "The beta-adrenoceptor of the human lymphocyte and human lung parenchyma. 1 The response of the beta-adrenoceptors of human lymphocytes to selective agonists and antagonists has been studied quantitatively by measuring changes in cyclic adenosine-3',5'-monophosphate (cyclic AMP) levels. 2 The receptor was activated by isoprenaline and by salbutamol, and blocked by propranolol but not by practolol. A similar pattern of response was obtained with fragments of human lung tissue. 3 The mean value for pA2 for propranolol was 8.34 and for practolol was 3.95. 4 These findings indicate that the lymphocyte beta-adrenoceptor is a beta2-receptor and support the solidity of using lymphocytes to study beta-adrenoceptor function in bronchial asthma. It may also be of use in the evaluation of selective beta2-blocking drugs in man."}
{"id": "PMID:13902", "title": "The selective action of beta-adrenoceptor blocking drugs and the nature of beta1 and beta2 adrenoceptors.", "content": "1 Purified membranes retaining a catecholamine responsive adenylate cyclase have prepared from rabbit heart, lung and (pseudo-pregnant) uterus. 2 These preparations have the characteristics of plasma membranes and both heart and lung respond to beta-adrenoceptor agonists in the order: (+/-)-isoprenaline greater than (-)-noradrenaline greater than (-)-adrenaline greater than (+)-isoprenaline greater than salbutamol. The sensitivity of the adenylate cyclase to beta-adrenoceptor stimulation is improved by pre-treatment of the animals with reserpine and syrosingopine. 3 Dose-ratios for several concentrations of propranolol (non-selective beta-adrenoceptor blocker), practolol and atenolol (cardio-selective beta-adrenoceptor blockers) have been measured on all three membrane preparations. Schild plots of log (dose ratio -1) vs. log dose were virtually coincident for heart and lung with a dissociation constant (Kb) for propranolol very close to the pharmacological value. The ratio of Kb values was 0.65 for practolol and 1.23 for atenolol compared with pharmacological cardio-selectivity ratios (measured on isolated atria and tracheal chain) of 67.6 and 110 respectively. The uterus/heart Kb ratio was 51.5 for atenolol. Inhibition of the uterus by practolol gave a Schild plot with slope significantly less than 1, indicating a different mechanism of action from the heart. 4 Kb values obtained by measuring adenylate cyclase stimulation in chopped tissue (including preparations of bronchial tree and alveolar tissue as well as whole lung) resembled the membrane values rather than those found in whole organs. 5 The results show that the pharmacological selectivity of practolol and atenolol is maintained at the receptor-adenylate cyclase level, at least as far as heart and uterus are concerned, though the smaller selectivity ratios in the biochemical system suggest that receptor differences is not the only factor and that phase distribution of the drug may also be important. Membranes prepared from whole lung show that phase distribution of the drug may also be important. Membranes prepared from whole lung show an overall beta1 response which may simply reflect the predominance of beta1 cell types containing beta1-adrenoceptors over bronchial smooth muscle.", "contents": "The selective action of beta-adrenoceptor blocking drugs and the nature of beta1 and beta2 adrenoceptors. 1 Purified membranes retaining a catecholamine responsive adenylate cyclase have prepared from rabbit heart, lung and (pseudo-pregnant) uterus. 2 These preparations have the characteristics of plasma membranes and both heart and lung respond to beta-adrenoceptor agonists in the order: (+/-)-isoprenaline greater than (-)-noradrenaline greater than (-)-adrenaline greater than (+)-isoprenaline greater than salbutamol. The sensitivity of the adenylate cyclase to beta-adrenoceptor stimulation is improved by pre-treatment of the animals with reserpine and syrosingopine. 3 Dose-ratios for several concentrations of propranolol (non-selective beta-adrenoceptor blocker), practolol and atenolol (cardio-selective beta-adrenoceptor blockers) have been measured on all three membrane preparations. Schild plots of log (dose ratio -1) vs. log dose were virtually coincident for heart and lung with a dissociation constant (Kb) for propranolol very close to the pharmacological value. The ratio of Kb values was 0.65 for practolol and 1.23 for atenolol compared with pharmacological cardio-selectivity ratios (measured on isolated atria and tracheal chain) of 67.6 and 110 respectively. The uterus/heart Kb ratio was 51.5 for atenolol. Inhibition of the uterus by practolol gave a Schild plot with slope significantly less than 1, indicating a different mechanism of action from the heart. 4 Kb values obtained by measuring adenylate cyclase stimulation in chopped tissue (including preparations of bronchial tree and alveolar tissue as well as whole lung) resembled the membrane values rather than those found in whole organs. 5 The results show that the pharmacological selectivity of practolol and atenolol is maintained at the receptor-adenylate cyclase level, at least as far as heart and uterus are concerned, though the smaller selectivity ratios in the biochemical system suggest that receptor differences is not the only factor and that phase distribution of the drug may also be important. Membranes prepared from whole lung show that phase distribution of the drug may also be important. Membranes prepared from whole lung show an overall beta1 response which may simply reflect the predominance of beta1 cell types containing beta1-adrenoceptors over bronchial smooth muscle."}
{"id": "PMID:13903", "title": "Mechanism of neurotoxicity of cardiotonic glycosides.", "content": "1 In cats intracerebroventricular administration of 5, 10, 20 mug of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 mug of ouabain, produced marked neurotoxicity. This was dose-related. 2 Prior administration reserpine (2 mg/kg i.m., 500 mug i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/,g i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/,g i.p., 2 mg 2.c.v.) and haloperidol (200 mug i.c.v.) were ineffective. 3 Prior administration of 2-bromolysergic acid diethylamide (BOL-148, 200 mug i.c.v.) or p-chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain. 4 Perfusion of the lateral ventricles of cats with 10, 20 and 30 mug of peruvoside or ouqbain produced a massive release of 5-hydroxytryptamine (5-HT). This was dose-related. Prior administration PCPA suppressed the release of 5-HT. 5 The results of the findings indicate the involvement of 5-HT in the genesis of neurotoxicity induced by peruvoside or ouabain.", "contents": "Mechanism of neurotoxicity of cardiotonic glycosides. 1 In cats intracerebroventricular administration of 5, 10, 20 mug of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 mug of ouabain, produced marked neurotoxicity. This was dose-related. 2 Prior administration reserpine (2 mg/kg i.m., 500 mug i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/,g i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/,g i.p., 2 mg 2.c.v.) and haloperidol (200 mug i.c.v.) were ineffective. 3 Prior administration of 2-bromolysergic acid diethylamide (BOL-148, 200 mug i.c.v.) or p-chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain. 4 Perfusion of the lateral ventricles of cats with 10, 20 and 30 mug of peruvoside or ouqbain produced a massive release of 5-hydroxytryptamine (5-HT). This was dose-related. Prior administration PCPA suppressed the release of 5-HT. 5 The results of the findings indicate the involvement of 5-HT in the genesis of neurotoxicity induced by peruvoside or ouabain."}
{"id": "PMID:13904", "title": "Crystalluria in normal subjects and in stone formers with and without thiazide and cellulose phosphate treatment.", "content": "Quantitative and qualitative studies have been made of the urinary crystals from a series of normal subjects and from stone formers with idiopathic hypercalciuria with and without treatment with thiazide diuretics and/or cellulose phosphate. The results obtained from mid-morning unprepared subjects seemed more helpful than those obtained following overnight collections or after a dry breakfast. Crystalluria was more common in stone formers than in normal subjects, but was seen in both groups. The most striking difference between these 2 groups was the almost complete absence of aggregation of oxalate crystals in the normal subjects. Cellulose phosphate greatly reduced phosphate crystals but resulted in a large increase in small oxalate crystals but without change in the incidence of aggregation of oxalate crystals. Thiazides also reduced occurrence of phosphate crystals but only gave a very small increase in oxalate crystals and also without change in aggregation of oxalate crystals.", "contents": "Crystalluria in normal subjects and in stone formers with and without thiazide and cellulose phosphate treatment. Quantitative and qualitative studies have been made of the urinary crystals from a series of normal subjects and from stone formers with idiopathic hypercalciuria with and without treatment with thiazide diuretics and/or cellulose phosphate. The results obtained from mid-morning unprepared subjects seemed more helpful than those obtained following overnight collections or after a dry breakfast. Crystalluria was more common in stone formers than in normal subjects, but was seen in both groups. The most striking difference between these 2 groups was the almost complete absence of aggregation of oxalate crystals in the normal subjects. Cellulose phosphate greatly reduced phosphate crystals but resulted in a large increase in small oxalate crystals but without change in the incidence of aggregation of oxalate crystals. Thiazides also reduced occurrence of phosphate crystals but only gave a very small increase in oxalate crystals and also without change in aggregation of oxalate crystals."}
{"id": "PMID:13906", "title": "Inhibition of gastric secretion in treatment of pancreatic insufficiency.", "content": "The content of pancreatic enzymes in the duodenum was studied in two patients with pancreatic achylia after a standard meal supplemented with commercial pancreatic extract. Gastric transit of the enzymes, with appearance of near-normal amounts in the duodenal contents, occurred only after inhibition of gastric secretion and buffering of residual gastric acid with antacids. Gastric inhibition and neutralisation of acid are therefore necessary for the satisfactory treatment of patients with pancreatic exocrine insufficiency but normal gastric function.", "contents": "Inhibition of gastric secretion in treatment of pancreatic insufficiency. The content of pancreatic enzymes in the duodenum was studied in two patients with pancreatic achylia after a standard meal supplemented with commercial pancreatic extract. Gastric transit of the enzymes, with appearance of near-normal amounts in the duodenal contents, occurred only after inhibition of gastric secretion and buffering of residual gastric acid with antacids. Gastric inhibition and neutralisation of acid are therefore necessary for the satisfactory treatment of patients with pancreatic exocrine insufficiency but normal gastric function."}
{"id": "PMID:13907", "title": "Electrical stimulation with Pt electrodes: Trace analysis for dissolved platinum and other dissolved electrochemical products.", "content": "A conservative requirement for 'safe' electrical stimulation is the absence of chemical changes adjacent to the stimulating electrodes. In electrochemical terms, this means that charge transfer processes producing dissolved species must be avoided. With this restriction, the aim of this study has been to establish the maximum charge density that can be passed during each half of a biphasic stimulation pulse. Possible dissolved species resulting from faradaic reactions at the Pt/saline interface include chloride oxidation products (ClO-, ClO3-, etc.) H+ or OH- ions and Pt ions. For balanced biphasic pulses, neither Cl- oxidation nor pH shifts appear likely to constitute significant problems and the most difficult problem to avoid appears to be metal dissolution. Pt dissolution has been monitored by UV spectrophotometric analysis and, because protein interferes with the analysis, the tests were run in inorganic saline solution. Results are presented in the form of nomographs which relate Pt dissolution to the charge density per pulse and the current density. Specific recommendations for minimizing Pt dissolution include the use of platinized electrodes, the restriction of charge densities per pulse to greater than or equal to 300 muC/geom cm2 of electrode surface, and preferably the use of cathodic-first biphasic pulses.", "contents": "Electrical stimulation with Pt electrodes: Trace analysis for dissolved platinum and other dissolved electrochemical products. A conservative requirement for 'safe' electrical stimulation is the absence of chemical changes adjacent to the stimulating electrodes. In electrochemical terms, this means that charge transfer processes producing dissolved species must be avoided. With this restriction, the aim of this study has been to establish the maximum charge density that can be passed during each half of a biphasic stimulation pulse. Possible dissolved species resulting from faradaic reactions at the Pt/saline interface include chloride oxidation products (ClO-, ClO3-, etc.) H+ or OH- ions and Pt ions. For balanced biphasic pulses, neither Cl- oxidation nor pH shifts appear likely to constitute significant problems and the most difficult problem to avoid appears to be metal dissolution. Pt dissolution has been monitored by UV spectrophotometric analysis and, because protein interferes with the analysis, the tests were run in inorganic saline solution. Results are presented in the form of nomographs which relate Pt dissolution to the charge density per pulse and the current density. Specific recommendations for minimizing Pt dissolution include the use of platinized electrodes, the restriction of charge densities per pulse to greater than or equal to 300 muC/geom cm2 of electrode surface, and preferably the use of cathodic-first biphasic pulses."}
{"id": "PMID:13909", "title": "The normal occurrence of octopamine in the central nervous system of the rat.", "content": "An enzymatic assay for octopamine capable of detecting 50 pg of amine was developed and used to study the distribution of octopamine in regions of the rat central nervous system. The presence of octopamine in the rat pineal organ was confirmed by mass spectrometry; Administration of a monoamine oxidase inhibitor and of tyramine led to increases in CNS octopamine levels while the administration of reserpine intraperitoneally or 6-hydroxydopamine intraventricularly led to decreases in octopamine levels. The results suggest that in the mammalian CNS octopamine is present in neural structures where it may be involved in synaptic function.", "contents": "The normal occurrence of octopamine in the central nervous system of the rat. An enzymatic assay for octopamine capable of detecting 50 pg of amine was developed and used to study the distribution of octopamine in regions of the rat central nervous system. The presence of octopamine in the rat pineal organ was confirmed by mass spectrometry; Administration of a monoamine oxidase inhibitor and of tyramine led to increases in CNS octopamine levels while the administration of reserpine intraperitoneally or 6-hydroxydopamine intraventricularly led to decreases in octopamine levels. The results suggest that in the mammalian CNS octopamine is present in neural structures where it may be involved in synaptic function."}
{"id": "PMID:13910", "title": "Substrate specificities of the two genetically distinct human brain beta-galactosidases.", "content": "The two human brain beta-galactosidases were solubilized and fractionated by Sephadex G-200 gel filtration, free from each other. Substrate specificities of the two enzymes were examined for galactosylceramide, lactosyl-[N-stearoyl]ceramide, lactosyl-[N-lignoceroyl]ceramide, galactosyl-N-acetylgalactosaminyl-[N-stearoyl]ceramide, lactosyl-[N-lignoceroyl]ceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]galactosyl-glucosylceramide (GMI-ganglioside), galactosyl-N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside), and 4-methylumbelliferyl beta-galactoside. Under appropriately optimized conditions, either of the two beta-galactosidases could hydrolyze all of the substrates, although with widely varying rates. Relative specific activities of galactosylceramide beta-galactosidase toward galactosylceramide, lactosyl-[N-steroyl]ceramide, lactosyl-[N-lignoceroyl]ceramide. GM1-ganglioside, asialo GM1-ganglioside, and 4-methylumbelliferyl beta-galactoside were 100, 510, 250, 39, 41 and 120, respectively. Relative specific activities of GM1-ganglioside beta-galactosidase toward the same series of the substrates were 0.3, 78, 19, 100, 150 and 240; However, the optimal assay conditions for any given natural substrate were sufficiently different for each beta-galactosidase so that diagnostic assays for the two genetic diseases due to beta-galactosidase deficiencies could be carried out in whole tissues. Since the relative distribution of the two enzymes vary greatly in different tissues, contributions by the two enzymes to degradation of the natural glycosphingolipids in vivo may well vary in different organs. These findings may have an important bearing on the biochemical pathogenesis of these genetic disorders.", "contents": "Substrate specificities of the two genetically distinct human brain beta-galactosidases. The two human brain beta-galactosidases were solubilized and fractionated by Sephadex G-200 gel filtration, free from each other. Substrate specificities of the two enzymes were examined for galactosylceramide, lactosyl-[N-stearoyl]ceramide, lactosyl-[N-lignoceroyl]ceramide, galactosyl-N-acetylgalactosaminyl-[N-stearoyl]ceramide, lactosyl-[N-lignoceroyl]ceramide, galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]galactosyl-glucosylceramide (GMI-ganglioside), galactosyl-N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM1-ganglioside), and 4-methylumbelliferyl beta-galactoside. Under appropriately optimized conditions, either of the two beta-galactosidases could hydrolyze all of the substrates, although with widely varying rates. Relative specific activities of galactosylceramide beta-galactosidase toward galactosylceramide, lactosyl-[N-steroyl]ceramide, lactosyl-[N-lignoceroyl]ceramide. GM1-ganglioside, asialo GM1-ganglioside, and 4-methylumbelliferyl beta-galactoside were 100, 510, 250, 39, 41 and 120, respectively. Relative specific activities of GM1-ganglioside beta-galactosidase toward the same series of the substrates were 0.3, 78, 19, 100, 150 and 240; However, the optimal assay conditions for any given natural substrate were sufficiently different for each beta-galactosidase so that diagnostic assays for the two genetic diseases due to beta-galactosidase deficiencies could be carried out in whole tissues. Since the relative distribution of the two enzymes vary greatly in different tissues, contributions by the two enzymes to degradation of the natural glycosphingolipids in vivo may well vary in different organs. These findings may have an important bearing on the biochemical pathogenesis of these genetic disorders."}
{"id": "PMID:13915", "title": "Effects of alkylation by dimethyl sulfate, nitrogen mustard, and mitomycin C on DNA structure as studied by the ethidium binding assay.", "content": "The extent of alkylation of DNA by dimethyl sulfate, nitrogen mustard, and the antibiotic mitomycin C is related to the resulting decrease in the fluorescence of intercalated ethidium. The fluorescence losses due to the first two types of reagents show a marked pH dependence, with greater losses of fluorescence being observed at alkaline pH values. At pH 11.6 the fluorescence shows a slow recovery, so that with low levels of methylation (4% deoxyguanosine residues modified) one observes complete return of fluorescence. We postulate that these phenomena are due to conversion of 7-methyldeoxyguanosine to the zwitterionic form, and partial denaturation of the DNA duplex with loss of ethidium binding sites. Hydroxide-ion-catalyzed imidazole ring opening, and the removal of the positive charge permits reannealing with concomitant return of the ethidium intercalation sites. This conclusion is substantiated by enzymatic hydrolysis of 14C-labelled methylated DNA and identifiions of the ethidium assay. The distinctly different behavior of mitomycin C confirms previous conclusions that its alkylation, preferentially on guanine, does not take part at the N-7 position.", "contents": "Effects of alkylation by dimethyl sulfate, nitrogen mustard, and mitomycin C on DNA structure as studied by the ethidium binding assay. The extent of alkylation of DNA by dimethyl sulfate, nitrogen mustard, and the antibiotic mitomycin C is related to the resulting decrease in the fluorescence of intercalated ethidium. The fluorescence losses due to the first two types of reagents show a marked pH dependence, with greater losses of fluorescence being observed at alkaline pH values. At pH 11.6 the fluorescence shows a slow recovery, so that with low levels of methylation (4% deoxyguanosine residues modified) one observes complete return of fluorescence. We postulate that these phenomena are due to conversion of 7-methyldeoxyguanosine to the zwitterionic form, and partial denaturation of the DNA duplex with loss of ethidium binding sites. Hydroxide-ion-catalyzed imidazole ring opening, and the removal of the positive charge permits reannealing with concomitant return of the ethidium intercalation sites. This conclusion is substantiated by enzymatic hydrolysis of 14C-labelled methylated DNA and identifiions of the ethidium assay. The distinctly different behavior of mitomycin C confirms previous conclusions that its alkylation, preferentially on guanine, does not take part at the N-7 position."}
{"id": "PMID:13916", "title": "Characterization and substrate specificity of fumarylacetoacetate fumarylhydrolase.", "content": "The molecular weight of fumarylacetoacetate fumarylhydrolase (EC 3.7.1.2) is 86 000 +/- 10 000, as determined by gel filtration. The enzyme appears to be a dimer with a monomer molecular weight of 38 000 - 43 000, as determined by gel electrophoresis, gel filtration in guanidine-hydrochloride, and ultracentrifugation. The subunits appear to be identical, as only one band is seen in gel electrophoresis, only one protein peak is detected in gel filtration in guanidine-hydrochloride, and only one amino-terminal amino acid (proline) is detected. Three free sulfhydryl groups per denatured monomer are detected by reaction with 5,5'-dithiobis(2-nitrobenzoic acid), while for the active enzyme only two sulfhydryl groups react with this reagent, The extinction coefficients at 260 and 280 nm, the amino acid composition, and the isoelectric point (6.7) of the enzyme are also reported. The enzyme catalyzes the hydrolysis of six 2,4-diketo acids and three 3,5-diketo acids tested. The Km of the substrates is similar but V varies by a factor of 120. The pH optimum is 7.3. The enzyme did not catalyze the hydrolysis of a number of esters tested.", "contents": "Characterization and substrate specificity of fumarylacetoacetate fumarylhydrolase. The molecular weight of fumarylacetoacetate fumarylhydrolase (EC 3.7.1.2) is 86 000 +/- 10 000, as determined by gel filtration. The enzyme appears to be a dimer with a monomer molecular weight of 38 000 - 43 000, as determined by gel electrophoresis, gel filtration in guanidine-hydrochloride, and ultracentrifugation. The subunits appear to be identical, as only one band is seen in gel electrophoresis, only one protein peak is detected in gel filtration in guanidine-hydrochloride, and only one amino-terminal amino acid (proline) is detected. Three free sulfhydryl groups per denatured monomer are detected by reaction with 5,5'-dithiobis(2-nitrobenzoic acid), while for the active enzyme only two sulfhydryl groups react with this reagent, The extinction coefficients at 260 and 280 nm, the amino acid composition, and the isoelectric point (6.7) of the enzyme are also reported. The enzyme catalyzes the hydrolysis of six 2,4-diketo acids and three 3,5-diketo acids tested. The Km of the substrates is similar but V varies by a factor of 120. The pH optimum is 7.3. The enzyme did not catalyze the hydrolysis of a number of esters tested."}
{"id": "PMID:13917", "title": "Kinetics of the hydrolysis of cellobiose and p-nitrophenyl-beta-D-glucoside by cellobiase of Trichoderma viride.", "content": "Cellobiase has been isolated from the crude cellulase mixture of enzymes of Trichoderma viride using column chromatographic and ion-exchange methods. The steady-state kinetics of the hydrolysis of cellobiose have been investigated as a function of cellobiose and glucose concentrations, pH of the solution, temperature, and dielectric constant, using isopropanol-buffer mixtures. The results show that (i) there is a marked activation of the reaction by initial glucose concentrations of 4 X 10(-3) M to 9 X 10(-2) M and strong inhibition of the reaction at higher initial concentrations, (ii) the log rate -pH curve has a maximum at pH 5.2 and enzyme pK values of 3.5 and 6.8, (iii) the energy of activation at pH 5.1 is 10.2 kcal mol-1 over the temperature range 5-56 degrees C, and (iv) the rate decreases from 0 to 20% (v/v) isopropanol. The hydrolysis by cellobiase (EC 3.2.1.21) of p-nitrophenyl-beta-D-glucoside was examined by pre-steady-state methods in which [enzyme]0 greater than [substrate]0, and by steady-state methods as a function of pH and temperature. The results show (i) a value for k2 of 21 S-1 at pH 7.0 (where k2 is the rate constant for the second step in the assumed two-intermediate mechanism (formula: see text), (ii) a log rate -pH curve, significantly different from that for hydrolysis of cellobiose, in which the rate increases with decreasing pH below pH 4.5, is constant in the region pH 4.5-6, and decreases above pH 6 (exhibiting an enzyme pK value of 7.3), and (iii) an activation energy of 12.5 kcal mol-1 at pH 5.7 over the temperature range 10-60 degrees C.", "contents": "Kinetics of the hydrolysis of cellobiose and p-nitrophenyl-beta-D-glucoside by cellobiase of Trichoderma viride. Cellobiase has been isolated from the crude cellulase mixture of enzymes of Trichoderma viride using column chromatographic and ion-exchange methods. The steady-state kinetics of the hydrolysis of cellobiose have been investigated as a function of cellobiose and glucose concentrations, pH of the solution, temperature, and dielectric constant, using isopropanol-buffer mixtures. The results show that (i) there is a marked activation of the reaction by initial glucose concentrations of 4 X 10(-3) M to 9 X 10(-2) M and strong inhibition of the reaction at higher initial concentrations, (ii) the log rate -pH curve has a maximum at pH 5.2 and enzyme pK values of 3.5 and 6.8, (iii) the energy of activation at pH 5.1 is 10.2 kcal mol-1 over the temperature range 5-56 degrees C, and (iv) the rate decreases from 0 to 20% (v/v) isopropanol. The hydrolysis by cellobiase (EC 3.2.1.21) of p-nitrophenyl-beta-D-glucoside was examined by pre-steady-state methods in which [enzyme]0 greater than [substrate]0, and by steady-state methods as a function of pH and temperature. The results show (i) a value for k2 of 21 S-1 at pH 7.0 (where k2 is the rate constant for the second step in the assumed two-intermediate mechanism (formula: see text), (ii) a log rate -pH curve, significantly different from that for hydrolysis of cellobiose, in which the rate increases with decreasing pH below pH 4.5, is constant in the region pH 4.5-6, and decreases above pH 6 (exhibiting an enzyme pK value of 7.3), and (iii) an activation energy of 12.5 kcal mol-1 at pH 5.7 over the temperature range 10-60 degrees C."}
{"id": "PMID:13918", "title": "The effect of chronic iron deficiency on adrenal tyrosine hydroxylase activity.", "content": "Chronic nutritional iron deficiency of 2 to 5 weeks duration reduced the blood hemoglobin content to 30-50% of control values and resulted in an increase in rat adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2) activity. Kinetic and mixing experiments indicated that this increase was due to an increase in enzyme protein. The body weight of iron-deficient rats ranged from 60 to 80% of control; this factor, however, was not responsible for the increase in adrenal TH as enzyme activity was directly proportional to final body weight. To determine whether the increase in adrenal TH in iron-deficient rats was due to increased sympathetic activity to the adrenal medulla, the splanchnic nerve was cut. The increased TH was still observed after adrenal denervation; this indicates that the mechanism of response to iron deficiency lies within the adrenal itself. Age of the rats is important in determining whether the increase in TH activity will occur.", "contents": "The effect of chronic iron deficiency on adrenal tyrosine hydroxylase activity. Chronic nutritional iron deficiency of 2 to 5 weeks duration reduced the blood hemoglobin content to 30-50% of control values and resulted in an increase in rat adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2) activity. Kinetic and mixing experiments indicated that this increase was due to an increase in enzyme protein. The body weight of iron-deficient rats ranged from 60 to 80% of control; this factor, however, was not responsible for the increase in adrenal TH as enzyme activity was directly proportional to final body weight. To determine whether the increase in adrenal TH in iron-deficient rats was due to increased sympathetic activity to the adrenal medulla, the splanchnic nerve was cut. The increased TH was still observed after adrenal denervation; this indicates that the mechanism of response to iron deficiency lies within the adrenal itself. Age of the rats is important in determining whether the increase in TH activity will occur."}
{"id": "PMID:13919", "title": "Isolation and characterization of a mitochondrial D-amino acid oxidase from Neurospora crassa.", "content": "D-Amino acid oxidase (EC 1.4.3.3) activity in homogenates of Neurospora crassa strain SY7A was found to sediment with the mitochondrial fraction. Digitonin fractionation studies on purified mitochondria have indicated a matrix localization of the enzyme. Additionally, a peroxidase (EC 1.11.1.7) activity, which may remove hydrogen peroxide formed as a product of D-amino acid oxidation, was also found in the mitochondrial matrix. Partial purification (20- to 30-fold) of the mitochondrial D-amino acid oxidase was achieved. The enzyme exhibited a pH optimum between 9.0 and 9.2, temperature optimum between 20 and 30 degrees C, and a molecular weight of 118 000 +/- 6000 as determined by gel electrophoresis and 125 000 as determined by gel chromatography.", "contents": "Isolation and characterization of a mitochondrial D-amino acid oxidase from Neurospora crassa. D-Amino acid oxidase (EC 1.4.3.3) activity in homogenates of Neurospora crassa strain SY7A was found to sediment with the mitochondrial fraction. Digitonin fractionation studies on purified mitochondria have indicated a matrix localization of the enzyme. Additionally, a peroxidase (EC 1.11.1.7) activity, which may remove hydrogen peroxide formed as a product of D-amino acid oxidation, was also found in the mitochondrial matrix. Partial purification (20- to 30-fold) of the mitochondrial D-amino acid oxidase was achieved. The enzyme exhibited a pH optimum between 9.0 and 9.2, temperature optimum between 20 and 30 degrees C, and a molecular weight of 118 000 +/- 6000 as determined by gel electrophoresis and 125 000 as determined by gel chromatography."}
{"id": "PMID:13920", "title": "Nicotinamide adenine dinucleotide -- independent formate dehydrogenase in Mycobacterium phlei.", "content": "Formate dehydrogenase activity (EC 1.2.1.2) has been demonstrated in cell-free preparations of Mycobacterium phlei by following the reduction of 2,6 dichlorophenolindophenol. thiazolyl blue tetrazolium, or equine cytochrome c. The reduction of equine cytochrome c was inhibited by 2-heptyl-4-hydroxyquinoline-N-oxide. Neither nicotinamide adenine dinucleotide nor nicotinamide adenine dinucleotide phosphate were reduced by this formate dehydrogenase. The enzyme was constitutive and associated with the particular fraction. The greatest level of activity was observed at pH 9.0, with 8 mM formate, and with extracts of cells taken from the log phase of growth. Formaldehyde, hypophosphite, nitrate, and bicarbonate all inhibited the oxidation of formate.", "contents": "Nicotinamide adenine dinucleotide -- independent formate dehydrogenase in Mycobacterium phlei. Formate dehydrogenase activity (EC 1.2.1.2) has been demonstrated in cell-free preparations of Mycobacterium phlei by following the reduction of 2,6 dichlorophenolindophenol. thiazolyl blue tetrazolium, or equine cytochrome c. The reduction of equine cytochrome c was inhibited by 2-heptyl-4-hydroxyquinoline-N-oxide. Neither nicotinamide adenine dinucleotide nor nicotinamide adenine dinucleotide phosphate were reduced by this formate dehydrogenase. The enzyme was constitutive and associated with the particular fraction. The greatest level of activity was observed at pH 9.0, with 8 mM formate, and with extracts of cells taken from the log phase of growth. Formaldehyde, hypophosphite, nitrate, and bicarbonate all inhibited the oxidation of formate."}
{"id": "PMID:13921", "title": "Effects of clear-cutting on the composition of bacterial populations of northern spruce forest soil.", "content": "This paper concerns the microbiological part of an investigation, the goal of which is to describe the biological changes in coniferous forest soil upon clear-cutting in a northern (66 degrees 20'N) moraine area where reforestation after clear-cutting had been met with difficulty. The zoological part of the work has been published elsewhere. Clear-cut sites of increasing age (4, 7, and 13 years) were investigated and compared with a forest area where no cutting of timber had been done for 120 years. A total of 684 random isolates of heterotrophic bacteria from pooled samples of the sites investigated were passed through 36 biochemical tests. The data were condensed by the aid of factor analysis, and a comparison of the populations was based on squared Euclidean distances between population centroids in a seven-dimensional factor space. The most marked population changes followed a course in which frequencies of some population characteristics became increasingly different until 7 years after clear-cutting, with regression towards the control clearly evident after 13 years. Disturbances of shorter duration were also relatively common, with maximal changes observed in the 4-year samples, and with a complete recovery after 7 years. The mineral soil populations seemed to undergo greater changes than the humus populations. The most distinct changes believed to be due to clear-cutting were the short-term relative increase of organisms producing acid from sucrose and dissolving CaHPO4, and a long-term increase of lipolytic and caseolytic, rhamnose-negative organisms; both in the mineral soil layer. In the humus layer, a short-term increase of lipolytic and of rhamnose-positive organisms seemed to take place.", "contents": "Effects of clear-cutting on the composition of bacterial populations of northern spruce forest soil. This paper concerns the microbiological part of an investigation, the goal of which is to describe the biological changes in coniferous forest soil upon clear-cutting in a northern (66 degrees 20'N) moraine area where reforestation after clear-cutting had been met with difficulty. The zoological part of the work has been published elsewhere. Clear-cut sites of increasing age (4, 7, and 13 years) were investigated and compared with a forest area where no cutting of timber had been done for 120 years. A total of 684 random isolates of heterotrophic bacteria from pooled samples of the sites investigated were passed through 36 biochemical tests. The data were condensed by the aid of factor analysis, and a comparison of the populations was based on squared Euclidean distances between population centroids in a seven-dimensional factor space. The most marked population changes followed a course in which frequencies of some population characteristics became increasingly different until 7 years after clear-cutting, with regression towards the control clearly evident after 13 years. Disturbances of shorter duration were also relatively common, with maximal changes observed in the 4-year samples, and with a complete recovery after 7 years. The mineral soil populations seemed to undergo greater changes than the humus populations. The most distinct changes believed to be due to clear-cutting were the short-term relative increase of organisms producing acid from sucrose and dissolving CaHPO4, and a long-term increase of lipolytic and caseolytic, rhamnose-negative organisms; both in the mineral soil layer. In the humus layer, a short-term increase of lipolytic and of rhamnose-positive organisms seemed to take place."}
{"id": "PMID:13922", "title": "[Study of the NADH and NADPH-ferredoxin oxidoreductase activities in Clostridium acetobutylicum].", "content": "The NADH and NADPH-ferredoxin oxidoreductase have been studied in Clostridium acetobutylicum. Acetyl-CoA is an obligatory activator of NADH-ferredoxin reductase activity and NADH a competitive inhibitor of ferredoxin-NAD+ reductase activity. These regulations are the same when C. acetoburylicum moves from 'butylic-type metabolism' to 'butyric-type metabolism'; this demonstrates that NADH-ferredoxin oxidoreductase cna, through its reversible action, meet the very different cell needs imposed by these two types of culture. The physiological function of the clostridial NADPH-ferredoxin oxidoreductase was anabolic as it has been with other clostridia.", "contents": "[Study of the NADH and NADPH-ferredoxin oxidoreductase activities in Clostridium acetobutylicum]. The NADH and NADPH-ferredoxin oxidoreductase have been studied in Clostridium acetobutylicum. Acetyl-CoA is an obligatory activator of NADH-ferredoxin reductase activity and NADH a competitive inhibitor of ferredoxin-NAD+ reductase activity. These regulations are the same when C. acetoburylicum moves from 'butylic-type metabolism' to 'butyric-type metabolism'; this demonstrates that NADH-ferredoxin oxidoreductase cna, through its reversible action, meet the very different cell needs imposed by these two types of culture. The physiological function of the clostridial NADPH-ferredoxin oxidoreductase was anabolic as it has been with other clostridia."}
{"id": "PMID:13926", "title": "Buffering capacity of the smoke of different tobaccos in relation to lung cancer risks.", "content": "A method of assessing \"buffering capacity\" is described for comparison of the degree of acidity of alkalinity of the smoke of different tobaccos as presented to the oral and respiratory tracts of the smoker. Nicotine is more readily absorbed from an alkaline than from an acid smoke. The smoker of tobaccos giving a smoke of acid buffering capacity, in order to achieve full nicotine satisfaction, tends to smoke more and to inhale more, thus increasing lung cancer risks, than the smoker of tobaccos giving smoke of less acid or of alkaline buffering capacity.", "contents": "Buffering capacity of the smoke of different tobaccos in relation to lung cancer risks. A method of assessing \"buffering capacity\" is described for comparison of the degree of acidity of alkalinity of the smoke of different tobaccos as presented to the oral and respiratory tracts of the smoker. Nicotine is more readily absorbed from an alkaline than from an acid smoke. The smoker of tobaccos giving a smoke of acid buffering capacity, in order to achieve full nicotine satisfaction, tends to smoke more and to inhale more, thus increasing lung cancer risks, than the smoker of tobaccos giving smoke of less acid or of alkaline buffering capacity."}
{"id": "PMID:13927", "title": "Cytochrome P-450 and the metabolism of vinyl chloride.", "content": "The oxidation of vinyl chloride to non-volatile products is dependent on NADPH and microsomal enzymes. The addition of vinyl chloride to microsomes causes a Type 1 spectra shift, similar to that seen for phenobarbital [11[ which indicates the direct involvement of a cytochrome P-450 species; this difference spectrum is characteristic of substrate binding to this type of enzyme. A glutathione conjugate is probably formed, perhaps via a reactive intermediate.", "contents": "Cytochrome P-450 and the metabolism of vinyl chloride. The oxidation of vinyl chloride to non-volatile products is dependent on NADPH and microsomal enzymes. The addition of vinyl chloride to microsomes causes a Type 1 spectra shift, similar to that seen for phenobarbital [11[ which indicates the direct involvement of a cytochrome P-450 species; this difference spectrum is characteristic of substrate binding to this type of enzyme. A glutathione conjugate is probably formed, perhaps via a reactive intermediate."}
{"id": "PMID:13928", "title": "beta-Hexosaminidase isozymes in human colonic carcinoma.", "content": "Isoelectric focusing of crude extracts demonstrated that human colonic carcinomas contained a higher proportion of beta-hexosaminidase B than beta-hexosaminidase A, while normal human colonic mucosa contained a higher proportion of the A form of the enzyme. Studies of the isolated isozymes showed that beta-hexosaminidase B was more stable to heat and more active at low pH than beta-hexosaminidase A. Kinetic studies revealed that the A and B forms of beta-hexosaminidase had essentially the same Km and Vmax for p-nitrophenyl-N-acetyl-beta-D-glucosaminide.", "contents": "beta-Hexosaminidase isozymes in human colonic carcinoma. Isoelectric focusing of crude extracts demonstrated that human colonic carcinomas contained a higher proportion of beta-hexosaminidase B than beta-hexosaminidase A, while normal human colonic mucosa contained a higher proportion of the A form of the enzyme. Studies of the isolated isozymes showed that beta-hexosaminidase B was more stable to heat and more active at low pH than beta-hexosaminidase A. Kinetic studies revealed that the A and B forms of beta-hexosaminidase had essentially the same Km and Vmax for p-nitrophenyl-N-acetyl-beta-D-glucosaminide."}
{"id": "PMID:13929", "title": "Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis.", "content": "Uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes from dogs, rats, or humans rapidly metabolized [3H]-N-hydroxy-2-naphthylamine (N-HO-2-NA) to a water-soluble product that yielded 98% of the parent N-hydroxy amine upon treatment with beta-glucuronidase. The metabolite was identified as N-(beta-1-glucosiduronyl)-N-hydroxy-2-naphthylamine from ultraviolet, infrared, and mass spectral analyses of the glucuronide and its nitrone derivative. Incubation of N-hydroxy-1-naphthylamine (N-HO-1-NA), N-hydroxy-4-aminobiphenyl (N-HO-ABP), or the N-hydroxy derivatives of 2-aminofluorene, 4-aminoazobenzene, or N-acetyl-2-aminofluorene with uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes also yielded water-soluble products. beta-Glucuronidase treatment released 80 to 90% of the [3H]-NHO-1-NA and [3H]-N-HO-ABP conjugates as tritiated ether-extractable derivatives. N-HO-1-NA, N-HO-2-NA, and N-HO-ABP and the glucuronides of these N-hydroxy arylamines were relatively stable and nonreactive near neutral pH. At pH 5, the N-glucuronide of N-HO-2-NA and the presumed N-glucuronides of N-HO-1-NA and N-HO-ABP were rapidly hydrolyzed to the N-hydroxy arylamines that were then converted to reactive derivatives capable of binding covalently to nucleic acids. These data support the concept that arylamine bladder carcinogens are N-oxidized and N-glucuronidated in the liver and that the N-glucuronides are transported to the urinary bladder. The hydrolysis of the glucuronides to N-hydroxy arylamines and the conversion of the latter derivatives to highly reactive electrophilic arylnitrenium ions in the normally acidic urine of dogs and humans may be critical reactions for tumor induction in the urinary bladder.", "contents": "Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. Uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes from dogs, rats, or humans rapidly metabolized [3H]-N-hydroxy-2-naphthylamine (N-HO-2-NA) to a water-soluble product that yielded 98% of the parent N-hydroxy amine upon treatment with beta-glucuronidase. The metabolite was identified as N-(beta-1-glucosiduronyl)-N-hydroxy-2-naphthylamine from ultraviolet, infrared, and mass spectral analyses of the glucuronide and its nitrone derivative. Incubation of N-hydroxy-1-naphthylamine (N-HO-1-NA), N-hydroxy-4-aminobiphenyl (N-HO-ABP), or the N-hydroxy derivatives of 2-aminofluorene, 4-aminoazobenzene, or N-acetyl-2-aminofluorene with uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes also yielded water-soluble products. beta-Glucuronidase treatment released 80 to 90% of the [3H]-NHO-1-NA and [3H]-N-HO-ABP conjugates as tritiated ether-extractable derivatives. N-HO-1-NA, N-HO-2-NA, and N-HO-ABP and the glucuronides of these N-hydroxy arylamines were relatively stable and nonreactive near neutral pH. At pH 5, the N-glucuronide of N-HO-2-NA and the presumed N-glucuronides of N-HO-1-NA and N-HO-ABP were rapidly hydrolyzed to the N-hydroxy arylamines that were then converted to reactive derivatives capable of binding covalently to nucleic acids. These data support the concept that arylamine bladder carcinogens are N-oxidized and N-glucuronidated in the liver and that the N-glucuronides are transported to the urinary bladder. The hydrolysis of the glucuronides to N-hydroxy arylamines and the conversion of the latter derivatives to highly reactive electrophilic arylnitrenium ions in the normally acidic urine of dogs and humans may be critical reactions for tumor induction in the urinary bladder."}
{"id": "PMID:13931", "title": "Angina in  hypertensive patients. With particular reference to the negative chronotropic effects of sympatholytic therapy.", "content": "There was no significant difference in the blood pressure and heart rate response of hypertensive patients with and without angina to standardised exercise on a treadmill before and after anti-hypertensive treatment. There was no improvement in exercise tolerance in the hypertensive patients with angina treated with bethanidine, debrisoquine or guanethidine despite a reduction of resting and exercise heart rates after treatment. The negative chronotropic effect of these sympatholytic drugs was less than that of oxprenolol or propranolol, but the hypotensive response was greater. Both of these beta-receptor blocking drug produced an an improvement in exercise tolerance in patients with angina either alone or in combination with other hypotensive therapy. The best control of blood pressure and angina was often achieved by a combination of a sympatholytic drug and beta-receptor blocking drug. In hypertensive patients treated for several years, angina at presentation was occassionally reduced by reduction of blood pressure. Later onset of angina appeared to be unrelated to control of hypertension but to be due to coincidental coronary occlusion. There was no evidence that myocardial infarction was precipitated by postural or exercise hypotension although these effects occasionally precipitated angina.", "contents": "Angina in  hypertensive patients. With particular reference to the negative chronotropic effects of sympatholytic therapy. There was no significant difference in the blood pressure and heart rate response of hypertensive patients with and without angina to standardised exercise on a treadmill before and after anti-hypertensive treatment. There was no improvement in exercise tolerance in the hypertensive patients with angina treated with bethanidine, debrisoquine or guanethidine despite a reduction of resting and exercise heart rates after treatment. The negative chronotropic effect of these sympatholytic drugs was less than that of oxprenolol or propranolol, but the hypotensive response was greater. Both of these beta-receptor blocking drug produced an an improvement in exercise tolerance in patients with angina either alone or in combination with other hypotensive therapy. The best control of blood pressure and angina was often achieved by a combination of a sympatholytic drug and beta-receptor blocking drug. In hypertensive patients treated for several years, angina at presentation was occassionally reduced by reduction of blood pressure. Later onset of angina appeared to be unrelated to control of hypertension but to be due to coincidental coronary occlusion. There was no evidence that myocardial infarction was precipitated by postural or exercise hypotension although these effects occasionally precipitated angina."}
{"id": "PMID:13933", "title": "Formaldehyde-induced fluorescence in the telencephalon and diencephalon of the eel (Anguilla anguilla l.). A fluorescence-microscopic and microspectrofluorometric investigation with special reference to the innervation of the pituitary.", "content": "In the telencephalon and diencephalon of the eel (Anguilla anguilla L.) formaldehyde-induced fluorescence was studied microscopically and microfluorometrically with special emphasis on the innervation of the pituitary. In the telencephalon fluorescent fibers contained predominantly noradrenaline fluorophores. Fluorescent nuclei could not be established. In the diencephalon fluorescent perikarya were found in: (1) the paraventricular organ (PVO), possessing either dopamine or, to a lesser extent, serotonin fluorophores; (2) the PVO-accompanying group, exhibiting spectral data resembling those of noradrenaline fluorophores; (3) the nucleus hypothalami anterior (NHA), a small paired group of catecholamine-containing cells posterior to the commissura transversa.--The nucleus lobi inferioris exhibited a high density of delicate, most probably dopamine-containing terminals, while fibers surrounding this nucleus contained noradrenaline fluorophores. A high density of fluorescent terminals containing dopamine and/or noradrenaline was found in the habenular complex. Fluorescent terminals in the pituitary contained fluorophores resembling either dopamine or noradrenaline. Fluorescent tracts entered the pituitary from different directions. A rostral, unpaired tract enters the neurointermediate lobe, as also verified experimentally. The rostral pars distalis receives two paired tracts, one from a rostral and one from a dorsal direction. The proximal pars distalis also receives two paired tracts, one from a dorsal and one from a posterior direction.", "contents": "Formaldehyde-induced fluorescence in the telencephalon and diencephalon of the eel (Anguilla anguilla l.). A fluorescence-microscopic and microspectrofluorometric investigation with special reference to the innervation of the pituitary. In the telencephalon and diencephalon of the eel (Anguilla anguilla L.) formaldehyde-induced fluorescence was studied microscopically and microfluorometrically with special emphasis on the innervation of the pituitary. In the telencephalon fluorescent fibers contained predominantly noradrenaline fluorophores. Fluorescent nuclei could not be established. In the diencephalon fluorescent perikarya were found in: (1) the paraventricular organ (PVO), possessing either dopamine or, to a lesser extent, serotonin fluorophores; (2) the PVO-accompanying group, exhibiting spectral data resembling those of noradrenaline fluorophores; (3) the nucleus hypothalami anterior (NHA), a small paired group of catecholamine-containing cells posterior to the commissura transversa.--The nucleus lobi inferioris exhibited a high density of delicate, most probably dopamine-containing terminals, while fibers surrounding this nucleus contained noradrenaline fluorophores. A high density of fluorescent terminals containing dopamine and/or noradrenaline was found in the habenular complex. Fluorescent terminals in the pituitary contained fluorophores resembling either dopamine or noradrenaline. Fluorescent tracts entered the pituitary from different directions. A rostral, unpaired tract enters the neurointermediate lobe, as also verified experimentally. The rostral pars distalis receives two paired tracts, one from a rostral and one from a dorsal direction. The proximal pars distalis also receives two paired tracts, one from a dorsal and one from a posterior direction."}
{"id": "PMID:13934", "title": "A chromatin-bound proteolytic activity with unique specificity for histone H2A.", "content": "A protease associated with purified calf thymus chromatin has been found to act exclusively upon histone H2A, yielding a single new protein species, cH2A. This fragment migrates faster than H2A in acrylamide gel electrophoresis under denaturing conditions. The cH2A was purified and subjected to amino acid analysis and partial sequencing by the use of carboxypeptidase A. These studies demonstrated that cH2A had been derived from the removal of fifteen amino acids from the carboxy-terminal end of the intact H2A molecule, and that valine114 was its new carboxy-terminal residue. This cleavage does not occur under low ionic strength conditions, where H2A is believed to approximate a random coil; rather, it requires high ionic strength conditions similar to those under which the H2A molecule undergoes radical secondary and tertiary structural changes. This dependence upon ionic strength implies that the proteolytic cleavage is conformation- as well as sequence-specific. The H2A-specific protease is of nuclear origin, since isolation of nuclei by methods designed to maximize or minimize cytoplasmic contamination does not affect the level of proteolytic activity associated with purified chromatin. This nuclear protease appears to be tightly associated with the chromatin in vivo, for 0.6 M NaCl will not free it from isolated chromatin. A concentration of 1.2 M NaCl is required to dissociate the protease as well as its substrate from chromatin. The relationship of this enzyme to previously reported chromatin-bound proteases is discussed.", "contents": "A chromatin-bound proteolytic activity with unique specificity for histone H2A. A protease associated with purified calf thymus chromatin has been found to act exclusively upon histone H2A, yielding a single new protein species, cH2A. This fragment migrates faster than H2A in acrylamide gel electrophoresis under denaturing conditions. The cH2A was purified and subjected to amino acid analysis and partial sequencing by the use of carboxypeptidase A. These studies demonstrated that cH2A had been derived from the removal of fifteen amino acids from the carboxy-terminal end of the intact H2A molecule, and that valine114 was its new carboxy-terminal residue. This cleavage does not occur under low ionic strength conditions, where H2A is believed to approximate a random coil; rather, it requires high ionic strength conditions similar to those under which the H2A molecule undergoes radical secondary and tertiary structural changes. This dependence upon ionic strength implies that the proteolytic cleavage is conformation- as well as sequence-specific. The H2A-specific protease is of nuclear origin, since isolation of nuclei by methods designed to maximize or minimize cytoplasmic contamination does not affect the level of proteolytic activity associated with purified chromatin. This nuclear protease appears to be tightly associated with the chromatin in vivo, for 0.6 M NaCl will not free it from isolated chromatin. A concentration of 1.2 M NaCl is required to dissociate the protease as well as its substrate from chromatin. The relationship of this enzyme to previously reported chromatin-bound proteases is discussed."}
{"id": "PMID:13935", "title": "Impairment of enzyme induction by glucocorticoids in Zajdela hepatoma cells.", "content": "Whereas glucocorticoids induce TAT, TRP, GPT in liver and only TAT in HTC cells, no hormonal effect on the synthesis of these enzymes was found in Zajdela hepatoma cells grown in vivo as an ascitic tumor, or in vitro as layer cultures. Although these cells remain uninducible, the hormone penetrates normally, but a strong decrease of the specific binding of cytosol and nuclear proteins with the hormone was observed. The impairment at the level of the hormone receptors could account for the non-inducibility of enzyme synthesis in ZHC cells.", "contents": "Impairment of enzyme induction by glucocorticoids in Zajdela hepatoma cells. Whereas glucocorticoids induce TAT, TRP, GPT in liver and only TAT in HTC cells, no hormonal effect on the synthesis of these enzymes was found in Zajdela hepatoma cells grown in vivo as an ascitic tumor, or in vitro as layer cultures. Although these cells remain uninducible, the hormone penetrates normally, but a strong decrease of the specific binding of cytosol and nuclear proteins with the hormone was observed. The impairment at the level of the hormone receptors could account for the non-inducibility of enzyme synthesis in ZHC cells."}
{"id": "PMID:13937", "title": "Michaelis--Menten kinetic analysis of the hepatic microsomal benzpyrene hydroxylase from control, phenobarbital- and methyl-3-cholanthrene-treated rats.", "content": "The sensitive fluorimetric assay for hydroxy-3-benzpyrene (3-OH-BP) described by Dehnen et al., was used to study the effect of microsomal membrane concentration of the benzpyrene hydroxylase activity. Microsomes from phenobarbital (PB) and methyl-3-cholanthrene (3-MC)-treated rats were used in comparison with the microsomal fraction from control animals. At very low protein concentration, benzpyrene hydroxylase follows as Michaelis--Menten type kinetics. When the concentration of microsomal membrane is higher than a minimal value (+/- 6 mug protein/ml) the Km increases with increasing concentration of protein due to competitive inhibition by reversible and non-specific binding of the substrate. The Ki's for such a binding have been calculated. Pretreatment of rats with 3-MC selectively shortens the time linearity, decreases the Ks value, and has no effect on Vmax, while the administration of PB prolongs the time linearity, decreases Vmax and does not modify the Ks. 3-MC and PB specifically act on cytochrome P-450 and do not modify the physico-chemical properties of the microsomal membrane as measured by the non-specific binding of benzpyrene (BP).", "contents": "Michaelis--Menten kinetic analysis of the hepatic microsomal benzpyrene hydroxylase from control, phenobarbital- and methyl-3-cholanthrene-treated rats. The sensitive fluorimetric assay for hydroxy-3-benzpyrene (3-OH-BP) described by Dehnen et al., was used to study the effect of microsomal membrane concentration of the benzpyrene hydroxylase activity. Microsomes from phenobarbital (PB) and methyl-3-cholanthrene (3-MC)-treated rats were used in comparison with the microsomal fraction from control animals. At very low protein concentration, benzpyrene hydroxylase follows as Michaelis--Menten type kinetics. When the concentration of microsomal membrane is higher than a minimal value (+/- 6 mug protein/ml) the Km increases with increasing concentration of protein due to competitive inhibition by reversible and non-specific binding of the substrate. The Ki's for such a binding have been calculated. Pretreatment of rats with 3-MC selectively shortens the time linearity, decreases the Ks value, and has no effect on Vmax, while the administration of PB prolongs the time linearity, decreases Vmax and does not modify the Ks. 3-MC and PB specifically act on cytochrome P-450 and do not modify the physico-chemical properties of the microsomal membrane as measured by the non-specific binding of benzpyrene (BP)."}
{"id": "PMID:13941", "title": "Responses of the cerebral circulation to hypercapnia and hypoxia after 7th cranial nerve transection in baboons.", "content": "It has been proposed that the responses of the cerebral circulation to hypoxia, hypercapnia and hypotension may be partially mediated by an autonomic reflex with receptors in the carotid body or sinus serving as sensors and the efferent limbs being the 7th cranial nerves. Transection of the 7th cranial nerve has been reported to impair the cerebral circulatory response to isolated chemoreceptor stimulation by hypoxia and hypercapnia. To test this hypothesis we measured cerebral blood flow (CBF) by an intra-arterial 133Xe technique in 10 baboons during periods of induced hypoxia and hypercapnia, both before and after transection of the 7th cranial nerve, We found that the responses of CBF were unaltered by either unilateral or bilateral section of the nerve. Our results showing the preservation of normal CBF responses, following transection, suggest that neurogenic control of the cerebral circulation by an autonomic reflex involving the 7th nerve is unlikely.", "contents": "Responses of the cerebral circulation to hypercapnia and hypoxia after 7th cranial nerve transection in baboons. It has been proposed that the responses of the cerebral circulation to hypoxia, hypercapnia and hypotension may be partially mediated by an autonomic reflex with receptors in the carotid body or sinus serving as sensors and the efferent limbs being the 7th cranial nerves. Transection of the 7th cranial nerve has been reported to impair the cerebral circulatory response to isolated chemoreceptor stimulation by hypoxia and hypercapnia. To test this hypothesis we measured cerebral blood flow (CBF) by an intra-arterial 133Xe technique in 10 baboons during periods of induced hypoxia and hypercapnia, both before and after transection of the 7th cranial nerve, We found that the responses of CBF were unaltered by either unilateral or bilateral section of the nerve. Our results showing the preservation of normal CBF responses, following transection, suggest that neurogenic control of the cerebral circulation by an autonomic reflex involving the 7th nerve is unlikely."}
{"id": "PMID:13942", "title": "Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.", "content": "To determine whether hypoxia directly affects pulmonary microvascular filtration of fluid or permeability to plasma proteins, we measured steady state lung lymph flow and protein transport in eight unanesthetized sheep breathing 10% O2 in N2 for 4 hours. We also studied three sheep breathing the same gas mixture for 48 hours. We surgically prepared the sheep to isolate and collect lung lymph and to measure average pulmonary arterial (Ppa) and left atrial (Pla) pressures. We placed a balloon catheter in the left atrium to elevate Pla. After recovery, the sheep breathed air through a tracheostomy for 2-4 hours, followed by 4 or 48 hours of hypoxia. In 13 4-hour studies, the average arterial PO2 fell from 97 to 38 torr; Ppa rose from 20 to 33 cm H2O; and lung lymph flow and lymph protein flow were unchanged. We also found that during 48-hour hypoxia, with a sustained elevation in Ppa and a decline in Pla, lymph flow and protein flow did not increase. In four sheep, we also raised Pla for 4 hours, followed by 4 hours of hypoxia with elevated Pla. Again, despite the added stress of elevated Pla, we found that lymph flow and lymph protein flow remained constant during hypoxia. We conclude that severe alveolar hypoxia, for 4 or 48 hours, alone or with increased pulmonary microvascular pressure, produced no change in lung fluid filtration or protein permeability, a finding supported by normal postmortem histology and extravascular lung water content.", "contents": "Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep. To determine whether hypoxia directly affects pulmonary microvascular filtration of fluid or permeability to plasma proteins, we measured steady state lung lymph flow and protein transport in eight unanesthetized sheep breathing 10% O2 in N2 for 4 hours. We also studied three sheep breathing the same gas mixture for 48 hours. We surgically prepared the sheep to isolate and collect lung lymph and to measure average pulmonary arterial (Ppa) and left atrial (Pla) pressures. We placed a balloon catheter in the left atrium to elevate Pla. After recovery, the sheep breathed air through a tracheostomy for 2-4 hours, followed by 4 or 48 hours of hypoxia. In 13 4-hour studies, the average arterial PO2 fell from 97 to 38 torr; Ppa rose from 20 to 33 cm H2O; and lung lymph flow and lymph protein flow were unchanged. We also found that during 48-hour hypoxia, with a sustained elevation in Ppa and a decline in Pla, lymph flow and protein flow did not increase. In four sheep, we also raised Pla for 4 hours, followed by 4 hours of hypoxia with elevated Pla. Again, despite the added stress of elevated Pla, we found that lymph flow and lymph protein flow remained constant during hypoxia. We conclude that severe alveolar hypoxia, for 4 or 48 hours, alone or with increased pulmonary microvascular pressure, produced no change in lung fluid filtration or protein permeability, a finding supported by normal postmortem histology and extravascular lung water content."}
{"id": "PMID:13940", "title": "[Preliminary results of an entomological survey of the potential arbovirus vectors in the French Territory of Afars and Issas].", "content": "The preliminary results of an entomological survey of the potential arbovirus vectors in the French Territory of Afars and Issas are exposed. 25 culicid species were recorded, specially Anopheles gambiae, Culex tritaeniorhynchus, C. univittatus, C. pipiens fatigans, Aedes caspius, Ae. vittatus, Ae. arabiensis. Ae. aegypti larvae were collected on a dhow arriving in Djibouti. 5 species of ticks and 4 sandfly speices were also recorded. The epidemiological modalities of certain arboviroses in this territory are discussed, depending on these entomological data and the uniterrupted travelling of local populations.", "contents": "[Preliminary results of an entomological survey of the potential arbovirus vectors in the French Territory of Afars and Issas]. The preliminary results of an entomological survey of the potential arbovirus vectors in the French Territory of Afars and Issas are exposed. 25 culicid species were recorded, specially Anopheles gambiae, Culex tritaeniorhynchus, C. univittatus, C. pipiens fatigans, Aedes caspius, Ae. vittatus, Ae. arabiensis. Ae. aegypti larvae were collected on a dhow arriving in Djibouti. 5 species of ticks and 4 sandfly speices were also recorded. The epidemiological modalities of certain arboviroses in this territory are discussed, depending on these entomological data and the uniterrupted travelling of local populations."}
{"id": "PMID:13943", "title": "Platelet aggregation in the cerebral microcirculation: effect of aspirin and other agents.", "content": "After a certain period of time filtered ultraviolet light produces platelet aggregation in microvessels on the cerebral surface of the mouse, but only when sodium fluorescein is first injected intravascularly to provide a light-absorbing, heat-generating target. The platelet aggregates fluoresce. They occur only in the illuminated field and adhere to arteriolar and venular walls. Vasoconstriction is not detected prior to or up to 30 seconds after aggregation. Electron microscopy reveals damaged endothelium and undamaged red cells, as well as aggregates consisting almost exclusively of platelets in varying stages of aggregation, pseudopod formation, and degranulation. The time between onset of the noxious stimulus and recognition of the first aggregate can be measured as the vessels are observed microscopically. This \"time of aggregation\" is prolonged by pentobarbital as opposed to urethane anesthesia, and also is related to time elapsed after craniotomy. We also found that aspirin and indomethacin significantly prolong time to first aggregate, but only on the arteriolar side of the circulation. This is so even though the composition of the aggregates is the same on both the arteriolar and venular sides. Heparin has no effect.", "contents": "Platelet aggregation in the cerebral microcirculation: effect of aspirin and other agents. After a certain period of time filtered ultraviolet light produces platelet aggregation in microvessels on the cerebral surface of the mouse, but only when sodium fluorescein is first injected intravascularly to provide a light-absorbing, heat-generating target. The platelet aggregates fluoresce. They occur only in the illuminated field and adhere to arteriolar and venular walls. Vasoconstriction is not detected prior to or up to 30 seconds after aggregation. Electron microscopy reveals damaged endothelium and undamaged red cells, as well as aggregates consisting almost exclusively of platelets in varying stages of aggregation, pseudopod formation, and degranulation. The time between onset of the noxious stimulus and recognition of the first aggregate can be measured as the vessels are observed microscopically. This \"time of aggregation\" is prolonged by pentobarbital as opposed to urethane anesthesia, and also is related to time elapsed after craniotomy. We also found that aspirin and indomethacin significantly prolong time to first aggregate, but only on the arteriolar side of the circulation. This is so even though the composition of the aggregates is the same on both the arteriolar and venular sides. Heparin has no effect."}
{"id": "PMID:13944", "title": "Use of equilibrated blood for internal blood-gas quality control.", "content": "We have used equilibrated human blood for blood-gas quality control since 1970. In blood equilibrated 24 h after shedding, gas tensions are stable for 4 to 6 h at 0 to 4 degrees C; each control specimen is analyzed several times during that period to resolve malfunctions, etc. Three-fourths of all errors in gas-tension measurement detected with equilibrated blood were detected with the highest-tension controls. Equilibrated blood controls signal about one error every 14 d on each instrument. For more complete quality control, we supplement analysis of equilibrated blood with other sorts of controls, comparing results obtained by assaying each patient's specimen on two instruments being our most effective adjunct. Such comparisons have identified erroneous assays in 3.9% of the specimens tested. The magnitude of interinstrument discrepancies (random errors) have ranged from 9 to 100% of the appropriate determinations. We use control data derived from equilibrated blood analysis for special management purposes (evaluating instruments, quantitating micro- vs. macro-sampling discrepancies, and decreasing instrument-repair costs).", "contents": "Use of equilibrated blood for internal blood-gas quality control. We have used equilibrated human blood for blood-gas quality control since 1970. In blood equilibrated 24 h after shedding, gas tensions are stable for 4 to 6 h at 0 to 4 degrees C; each control specimen is analyzed several times during that period to resolve malfunctions, etc. Three-fourths of all errors in gas-tension measurement detected with equilibrated blood were detected with the highest-tension controls. Equilibrated blood controls signal about one error every 14 d on each instrument. For more complete quality control, we supplement analysis of equilibrated blood with other sorts of controls, comparing results obtained by assaying each patient's specimen on two instruments being our most effective adjunct. Such comparisons have identified erroneous assays in 3.9% of the specimens tested. The magnitude of interinstrument discrepancies (random errors) have ranged from 9 to 100% of the appropriate determinations. We use control data derived from equilibrated blood analysis for special management purposes (evaluating instruments, quantitating micro- vs. macro-sampling discrepancies, and decreasing instrument-repair costs)."}
{"id": "PMID:13945", "title": "Lipoxygenic micromethod for specific determination of lipase activity in serum and duodenal fluid.", "content": "We propose a rapid enzymatic micromethod for the specific determination of lipase (EC 3.1.1.3) activity in serum and duodenal fluid. Free linoleic acid produced during 10-min incubation of 10 mul of sample with 1 ml of substrate (trillinolein emulsion) at 30 degrees C is converted by lipoxygenase (EC 1.99.2.1), in a coupled reaction, to its hydroperoxide, which is measured photometrically after solubilizing the reaction mixture in ethanol. Lipase activity is calculated from the rate of hydroperoxide formation, with linoleic acid as primary standard. The velocity of the reaction is greatest at pH 8.8, 35-37 degrees C, and a deoxycholate concentration of 3.6 mmol/liter. The energy of activation is 6.7 kcal/mol. The differing \"apparent\" Km values obtained for lipase in undiluted serum (4 X 10(-5) mol/liter) and in albumin-based diluents (1 X 10(-5) mol/liter) indicate the presence of a competitive inhibitor in the serum matrix. We detected no lipase activity in urine. Results by the proposed method correlate well with those by a copper soap extraction method (r = 0.95), but values are significantly higher for pancreatitis patients' sera (slope 1.6). The linear dynamic range extends to 1000 U/liter. Hemolysis, lipemia, and hyperbilirubinemia do not interfere. The normal range is 40-60 U/liter. Lipase activity of pancreatitis patients generally exceed 1000 U/liter during the acute phase and 250 U/liter for as long as 10 days after it.", "contents": "Lipoxygenic micromethod for specific determination of lipase activity in serum and duodenal fluid. We propose a rapid enzymatic micromethod for the specific determination of lipase (EC 3.1.1.3) activity in serum and duodenal fluid. Free linoleic acid produced during 10-min incubation of 10 mul of sample with 1 ml of substrate (trillinolein emulsion) at 30 degrees C is converted by lipoxygenase (EC 1.99.2.1), in a coupled reaction, to its hydroperoxide, which is measured photometrically after solubilizing the reaction mixture in ethanol. Lipase activity is calculated from the rate of hydroperoxide formation, with linoleic acid as primary standard. The velocity of the reaction is greatest at pH 8.8, 35-37 degrees C, and a deoxycholate concentration of 3.6 mmol/liter. The energy of activation is 6.7 kcal/mol. The differing \"apparent\" Km values obtained for lipase in undiluted serum (4 X 10(-5) mol/liter) and in albumin-based diluents (1 X 10(-5) mol/liter) indicate the presence of a competitive inhibitor in the serum matrix. We detected no lipase activity in urine. Results by the proposed method correlate well with those by a copper soap extraction method (r = 0.95), but values are significantly higher for pancreatitis patients' sera (slope 1.6). The linear dynamic range extends to 1000 U/liter. Hemolysis, lipemia, and hyperbilirubinemia do not interfere. The normal range is 40-60 U/liter. Lipase activity of pancreatitis patients generally exceed 1000 U/liter during the acute phase and 250 U/liter for as long as 10 days after it."}
{"id": "PMID:13946", "title": "D-Glucaric acid and gamma-glutamyltransferase as indices of hepatic enzyme induction in pregnancy.", "content": "Increased activity of hepatic microsomal enzymes can be evaluated by measuring D-glucaric acid excretion in urine and gamma-glutamyltransferase (EC 2.3.2.2) activity in serum. Aside from diverse foreign compounds, endogenous steroid hormones have been shown to be normal substrates of the microsomal enzyme system. Because there is an increase in steroid production in pregnancy, we sought to determine whether these indices of induction increase during pregnancy. In 90 women in various stages of pregnancy, all with normal kidney function, we measured glucaric acid excretion in urine and activity of the transferase in serum and in urine. Glucaric acid increased markedly during pregnancy, from 14.4 +/- 2.1 in the first trimester to 23.5 +/- 2.8 mumol of D-glucaro-1,4-lactone per gram of creatinine in the third trimester. We saw no correlation between glucaric acid excretion and the transferase activity in serum or urine. Activity of gamma-glutamyl-transferase remains within normal limits throughout pregnancy, which leaves doubt as to the value of this measurement in evaluating enzyme induction owing to endogenous steroids.", "contents": "D-Glucaric acid and gamma-glutamyltransferase as indices of hepatic enzyme induction in pregnancy. Increased activity of hepatic microsomal enzymes can be evaluated by measuring D-glucaric acid excretion in urine and gamma-glutamyltransferase (EC 2.3.2.2) activity in serum. Aside from diverse foreign compounds, endogenous steroid hormones have been shown to be normal substrates of the microsomal enzyme system. Because there is an increase in steroid production in pregnancy, we sought to determine whether these indices of induction increase during pregnancy. In 90 women in various stages of pregnancy, all with normal kidney function, we measured glucaric acid excretion in urine and activity of the transferase in serum and in urine. Glucaric acid increased markedly during pregnancy, from 14.4 +/- 2.1 in the first trimester to 23.5 +/- 2.8 mumol of D-glucaro-1,4-lactone per gram of creatinine in the third trimester. We saw no correlation between glucaric acid excretion and the transferase activity in serum or urine. Activity of gamma-glutamyl-transferase remains within normal limits throughout pregnancy, which leaves doubt as to the value of this measurement in evaluating enzyme induction owing to endogenous steroids."}
{"id": "PMID:13950", "title": "Ganglioside GM2 N-acetyl-beta-D-galactosaminidase and asialo GM2 (GA2) N-acetyl-beta-D-galactosaminidase; studies in human skin fibroblasts.", "content": "Ganglioside GM2 and its asialo-derivative, GA2 were radiolabeled in their N-acetyl-D-galactosaminyl moieties by oxidation with galactose oxidase and reduction with tritiated sodium borohydride. Specific activities of 6 X 10(4) dpm/nmol (GM2) and 1.8 X 10(6) dpm/nmol (GA2) were achieved. About 98% of the label was in N-acetyl-D-galactosamine. Using these substrates, an assay was developed for GM2-N-acetyl-beta-D-galactosaminidase (E.C.3.2.1.30) and GA2-N-acetyl-beta-D-galactosaminidase (E.C.3.2.1.30) activities in human cultured skin fibroblasts. The products of the GM2 cleaving reaction were identified as N-acetylgalactosamine and ganglioside GM3. Both GM2 and GA2 cleaving activities were stimulated about 5-fold by purified sodium taurocholate, and this stimulation was inhibited by neutral detergents, lipids and albumin at low concentrations. Addition of various salts, reducing agents and a protein activator factor from human liver of Li et al. (1973) did not stimulate GM2-N-acetyl-beta-D-galactosaminidase activity beyond that found with sodium taurocholate. Under optimal conditions, control fibroblast supernates cleaved ganglioside GM2 at a rate of 3.7 nmol/mg protein/h compared to 1100 for GA2-N-acetyl-beta-D-galactosaminidase and 4700 for 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminidase. Supernates from two patients with Tay-Sachs disease had markedly reduced activity levels for GM2-N-acetyl-beta-D-galactosaminidase but not for the other two substrates. Supernates from two patients with Sandhoff's disease had reduced activities for all three substrates. A supernate from one patient with juvenile GM2 gangliosidosis cleaved GM2 at a somewhat faster rate than those from Tay-Sachs or Sandhoff's patients. Two healthy adult women with markedly reduced hexosaminidase A activities using 4MU-N-acetyl-beta-D-glucosaminide as substrate had approximately half-normal activities using GM2 as substrate. A patient with the Tay-Sachs phenotype but with a partial deficiency of hexosaminidase A using the 4-MU substrate had a profound deficiency using GM2 as substrate. In such unusual hexosaminidase mutants, assays using GM2 as substrate are better indicators of phenotype than those using synthetic substrates.", "contents": "Ganglioside GM2 N-acetyl-beta-D-galactosaminidase and asialo GM2 (GA2) N-acetyl-beta-D-galactosaminidase; studies in human skin fibroblasts. Ganglioside GM2 and its asialo-derivative, GA2 were radiolabeled in their N-acetyl-D-galactosaminyl moieties by oxidation with galactose oxidase and reduction with tritiated sodium borohydride. Specific activities of 6 X 10(4) dpm/nmol (GM2) and 1.8 X 10(6) dpm/nmol (GA2) were achieved. About 98% of the label was in N-acetyl-D-galactosamine. Using these substrates, an assay was developed for GM2-N-acetyl-beta-D-galactosaminidase (E.C.3.2.1.30) and GA2-N-acetyl-beta-D-galactosaminidase (E.C.3.2.1.30) activities in human cultured skin fibroblasts. The products of the GM2 cleaving reaction were identified as N-acetylgalactosamine and ganglioside GM3. Both GM2 and GA2 cleaving activities were stimulated about 5-fold by purified sodium taurocholate, and this stimulation was inhibited by neutral detergents, lipids and albumin at low concentrations. Addition of various salts, reducing agents and a protein activator factor from human liver of Li et al. (1973) did not stimulate GM2-N-acetyl-beta-D-galactosaminidase activity beyond that found with sodium taurocholate. Under optimal conditions, control fibroblast supernates cleaved ganglioside GM2 at a rate of 3.7 nmol/mg protein/h compared to 1100 for GA2-N-acetyl-beta-D-galactosaminidase and 4700 for 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminidase. Supernates from two patients with Tay-Sachs disease had markedly reduced activity levels for GM2-N-acetyl-beta-D-galactosaminidase but not for the other two substrates. Supernates from two patients with Sandhoff's disease had reduced activities for all three substrates. A supernate from one patient with juvenile GM2 gangliosidosis cleaved GM2 at a somewhat faster rate than those from Tay-Sachs or Sandhoff's patients. Two healthy adult women with markedly reduced hexosaminidase A activities using 4MU-N-acetyl-beta-D-glucosaminide as substrate had approximately half-normal activities using GM2 as substrate. A patient with the Tay-Sachs phenotype but with a partial deficiency of hexosaminidase A using the 4-MU substrate had a profound deficiency using GM2 as substrate. In such unusual hexosaminidase mutants, assays using GM2 as substrate are better indicators of phenotype than those using synthetic substrates."}
{"id": "PMID:13951", "title": "Injuries of the forefoot.", "content": "Dislocations and fracture-dislocations of the tarsometatarsal joints, fractures of the base of the fifth metatarsal bone, fractures of the shafts and necks of the metatarsal bones, dislocations of the metatarsophalangeal joints, fractures of the phalanges and dislocations of the interphalangeal joints each have a specific mechanism of injury, characteristic diagnostic feature, and requirement for treatment. Only by an accurate diagnosis established by careful physical and roentgenographic examination can complications be avoided.", "contents": "Injuries of the forefoot. Dislocations and fracture-dislocations of the tarsometatarsal joints, fractures of the base of the fifth metatarsal bone, fractures of the shafts and necks of the metatarsal bones, dislocations of the metatarsophalangeal joints, fractures of the phalanges and dislocations of the interphalangeal joints each have a specific mechanism of injury, characteristic diagnostic feature, and requirement for treatment. Only by an accurate diagnosis established by careful physical and roentgenographic examination can complications be avoided."}
{"id": "PMID:13952", "title": "Injuries of the hindfoot.", "content": "Although the long term prognosis for many injuries of the hind foot is poor, prompt diagnosis and treatment can lead to a satisfactory result. Failure to treat these injuries promptly can lead to circulatory problems and skin necrosis. Stiffness and post-traumatic arthritis may occur despite adequate treatment due to the complex anatomy of the region. With the exception of certain rare fractures of the os calcis, displaced fractures of the talar neck and body and fracture-dislocations, injuries in this region of the foot heal best after closed treatment and early mobilization of the ankle and foot. Associated bodily injuries elsewhere, particularly those involving the spine, ankle, and tarsometatarsal joints should be anticipated in extensive injuries of the hind foot.", "contents": "Injuries of the hindfoot. Although the long term prognosis for many injuries of the hind foot is poor, prompt diagnosis and treatment can lead to a satisfactory result. Failure to treat these injuries promptly can lead to circulatory problems and skin necrosis. Stiffness and post-traumatic arthritis may occur despite adequate treatment due to the complex anatomy of the region. With the exception of certain rare fractures of the os calcis, displaced fractures of the talar neck and body and fracture-dislocations, injuries in this region of the foot heal best after closed treatment and early mobilization of the ankle and foot. Associated bodily injuries elsewhere, particularly those involving the spine, ankle, and tarsometatarsal joints should be anticipated in extensive injuries of the hind foot."}
{"id": "PMID:13954", "title": "Altered hepatic blood flow and drug disposition.", "content": "For some drugs, delivery to the liver by the hepatic circulation is an important determinant of removal by this organ. Classical pharmacokinetic analyses cannot predict the changes produced by altering any of the biological determinants of drug elimination by the liver; hepatic blood flow, metabolic enzyme activity, drug binding and route of administration. However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid. Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice logical changes affecting the circulation. For drug clearance to be affected significantly by these changes in flow, the drug must be avidly removed by the liver as reflected in a high hepatic extraction ratio and intrinsic hepatic clearance. This latter term is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation. The clearance of drugs with low intrinsic clearance will not be affected significantly by changes in liver blood flow.", "contents": "Altered hepatic blood flow and drug disposition. For some drugs, delivery to the liver by the hepatic circulation is an important determinant of removal by this organ. Classical pharmacokinetic analyses cannot predict the changes produced by altering any of the biological determinants of drug elimination by the liver; hepatic blood flow, metabolic enzyme activity, drug binding and route of administration. However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid. Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice logical changes affecting the circulation. For drug clearance to be affected significantly by these changes in flow, the drug must be avidly removed by the liver as reflected in a high hepatic extraction ratio and intrinsic hepatic clearance. This latter term is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation. The clearance of drugs with low intrinsic clearance will not be affected significantly by changes in liver blood flow."}
{"id": "PMID:13953", "title": "Lacerations of the plantar aspect of the foot.", "content": "The absence of any known reference in the medical literature to lacerations of the plantar aspect of the foot prompted the author to send an questionnaire to members of the American Orthopaedic Foot Society and Association of Bone and Joint Surgeons asking each one to outline his treatment for various combinations of lacerations of the flexor tendons and plantar nerves in a group of patients with varied ages and occupations. To simplify results, only clean wounds satisfactory for immediate surgery were considered. A majority of surgeons preferred primary repair of a lacerated flexor hallucis longus tendon or extensive laceration of all flexor tendons and nerves but were equally divided between repair and non-repair of flexor tendons and plantar nerves of the middle three toes. A majority of surgeons preferred not to repair isolated lacerations of flexor tendons other than the flexor hallucis longus. Most surgeons electing to repair the structures preferred to approach them through the original plantar laceration rather than through an accessory incision in the non weight-bearing portion of the foot.", "contents": "Lacerations of the plantar aspect of the foot. The absence of any known reference in the medical literature to lacerations of the plantar aspect of the foot prompted the author to send an questionnaire to members of the American Orthopaedic Foot Society and Association of Bone and Joint Surgeons asking each one to outline his treatment for various combinations of lacerations of the flexor tendons and plantar nerves in a group of patients with varied ages and occupations. To simplify results, only clean wounds satisfactory for immediate surgery were considered. A majority of surgeons preferred primary repair of a lacerated flexor hallucis longus tendon or extensive laceration of all flexor tendons and nerves but were equally divided between repair and non-repair of flexor tendons and plantar nerves of the middle three toes. A majority of surgeons preferred not to repair isolated lacerations of flexor tendons other than the flexor hallucis longus. Most surgeons electing to repair the structures preferred to approach them through the original plantar laceration rather than through an accessory incision in the non weight-bearing portion of the foot."}
{"id": "PMID:13955", "title": "Clincial pharmacokinetics in neonates.", "content": "Recent concern over toxic effects of drugs in newborns, infants and children have stressed the need for better knowledge of drug kinetics during development. The present review focuses on the available data on clinical pharmacokientics in the neonate. Despite the lack of systematic approaches on drug disposition during the first month of life, the body of data currently available indicates profound differences in drug disposition between neonates and older infants, children and adults. In terms of physiological and anatomical factors the neonate has to be considered as a 'unique drug recipient'. For all the specific variables which govern the drug kinetic pattern (absorption, blood esterase activity, plasma protein binding, metabolic degradation and renal excretion), there are clear difference between neonates and older infants and children. Such differences are not always unidirectional. In the case of absorption, they depend on the maturational stage, but more on the physico-chemical properties of the individual compound. Esterase activiy and renal excretion are also related to the physico-chemical properties of the drug, but are more clearly linked with the development stage. Plasma protein blinding is generally reduced, and depends on several factors, not all of which are as yet clearly identified and understood. Biotransformation activities are usually very low, but may be increased several-fold by exposure to inducing agents. Hydroxylating activity and conjugation with glucronic acid appear to be the two metabolic pathways which are most defective at birth, while sulphate and gylcine conjugation, and dealkylation activities are close to the adult pattern. The material reviewed is fragmentary and does not always permit a comparison of the data obtained in newborns with those reported for adults. Differences in the methodology used and in the kinetic criteria further complicate the matter. It is, however, clearly emerging that drug disposition may vary greatly in the newborn in relation to its developmental age. The reported differences may be relevant for clinical practice and stress the need for more detailed information on drug kinetics in the neonate. Such information may be achieved by carefully planned clinical trials, but more meaningfully, and more profitably for the individual patient, by a very carefully, well integrated monitoring of the neonate a risk. By such an approach, where drug plasma levels are related to drug effects and to the pathophysiological condition, the significance of various factors on drug disportion during development will be better clarified, thus allowing a more rational and safer therapy in the newborn.", "contents": "Clincial pharmacokinetics in neonates. Recent concern over toxic effects of drugs in newborns, infants and children have stressed the need for better knowledge of drug kinetics during development. The present review focuses on the available data on clinical pharmacokientics in the neonate. Despite the lack of systematic approaches on drug disposition during the first month of life, the body of data currently available indicates profound differences in drug disposition between neonates and older infants, children and adults. In terms of physiological and anatomical factors the neonate has to be considered as a 'unique drug recipient'. For all the specific variables which govern the drug kinetic pattern (absorption, blood esterase activity, plasma protein binding, metabolic degradation and renal excretion), there are clear difference between neonates and older infants and children. Such differences are not always unidirectional. In the case of absorption, they depend on the maturational stage, but more on the physico-chemical properties of the individual compound. Esterase activiy and renal excretion are also related to the physico-chemical properties of the drug, but are more clearly linked with the development stage. Plasma protein blinding is generally reduced, and depends on several factors, not all of which are as yet clearly identified and understood. Biotransformation activities are usually very low, but may be increased several-fold by exposure to inducing agents. Hydroxylating activity and conjugation with glucronic acid appear to be the two metabolic pathways which are most defective at birth, while sulphate and gylcine conjugation, and dealkylation activities are close to the adult pattern. The material reviewed is fragmentary and does not always permit a comparison of the data obtained in newborns with those reported for adults. Differences in the methodology used and in the kinetic criteria further complicate the matter. It is, however, clearly emerging that drug disposition may vary greatly in the newborn in relation to its developmental age. The reported differences may be relevant for clinical practice and stress the need for more detailed information on drug kinetics in the neonate. Such information may be achieved by carefully planned clinical trials, but more meaningfully, and more profitably for the individual patient, by a very carefully, well integrated monitoring of the neonate a risk. By such an approach, where drug plasma levels are related to drug effects and to the pathophysiological condition, the significance of various factors on drug disportion during development will be better clarified, thus allowing a more rational and safer therapy in the newborn."}
{"id": "PMID:13956", "title": "Renal failure, drug pharmacokinetics and drug action.", "content": "Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. Since the risk of retention concerns only those drugs which are mainly excreted by the kidney, it is possible to establish a mathematical relationship between glomerular filtration rate and the rate of drug elimination. These relationships serve as a basis for the determination of the proper dosage regimen for the individual patient. Such dosage adaptation for intermitten drug administration can be obtained by two methods and a series of compromises between them: (1) increase of the dosage interval without changing the dose, and (2) reduction of the does without changing the frequency of administration. One must however, not only consider inadequate drug elimination but also a number of other  factors. Some of these modify the behaviour of the drug, such as hypoalbumineamia, which causes an increase of the unbound portion of the drug; anomalies of the volume of distribution, as found in patients with oedema; metabolic disturbance; alteration of absorption from the gastro-intestinal tract, etc. Other factors are related only indirectly to the pharmacokinetic behaviour of the drug. Frequently, there is an increased sensitivity to the undesirable side-effects of certain drugs in patients with renal insufficiency, causing the level of tolerance to be lowered compared with normal patients. Such an effect probably involves functional or morphological modifications of the drug receptors, or interaction with substance retained in renal insufficiency. Furthermore, drugs may accentuate the consequences of the nephropathy or have increased nephrotoxicity for those with diseased kidneys. It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity.", "contents": "Renal failure, drug pharmacokinetics and drug action. Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. Since the risk of retention concerns only those drugs which are mainly excreted by the kidney, it is possible to establish a mathematical relationship between glomerular filtration rate and the rate of drug elimination. These relationships serve as a basis for the determination of the proper dosage regimen for the individual patient. Such dosage adaptation for intermitten drug administration can be obtained by two methods and a series of compromises between them: (1) increase of the dosage interval without changing the dose, and (2) reduction of the does without changing the frequency of administration. One must however, not only consider inadequate drug elimination but also a number of other  factors. Some of these modify the behaviour of the drug, such as hypoalbumineamia, which causes an increase of the unbound portion of the drug; anomalies of the volume of distribution, as found in patients with oedema; metabolic disturbance; alteration of absorption from the gastro-intestinal tract, etc. Other factors are related only indirectly to the pharmacokinetic behaviour of the drug. Frequently, there is an increased sensitivity to the undesirable side-effects of certain drugs in patients with renal insufficiency, causing the level of tolerance to be lowered compared with normal patients. Such an effect probably involves functional or morphological modifications of the drug receptors, or interaction with substance retained in renal insufficiency. Furthermore, drugs may accentuate the consequences of the nephropathy or have increased nephrotoxicity for those with diseased kidneys. It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity."}
{"id": "PMID:13957", "title": "The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone.", "content": "This review illustrates current approaches to the study of the disposition in man of the strong analagesics morphine and methadone and the narcotic antagonist naloxone. Morphine administered orally is rapidly absorbed but equally rapidly metabolised to morphine glucuronide. This contributes to the diminished oral efficacy of morphine. Following intramuscular administration morphine is very rapidly absorbed. After intravenous injection, the serum levels of morphine during the first 10 minutes are higher and more variable in older patients. The half-life of morphine between 20 minutes and 6 hours is 2 to 3 hours and this value does not appear to be influenced by the age of the patient. Similar half-lives for morphine have been reported to normal volunteers and in anaethetised patients who received morphine. Thus, surgical anaesthesia may not markedly influence morphine half-life and disposition. Based on urinary excretion data in man, accelerated morphine metabolism and excretion do not contribute to morphine tolerance. Methadone is now widely used in the treatment of narcotic abuse. The half-life of methadone averages 25 hours. The prolonged retention of methadone in the plasma may be related to its extensive binding to plasma proteins. With chronic dosing, studies in both animals and man indicate an increase in the metabolism of methadone. Unlike morphine, the urinary excretion of methadone increases with acidification of the urine. Women may metabolise methadone to a greater extent than do men. With the exception of pupillary effects, the plasma levels of methadone correlate poorly with its pharmacological activity. There is a marked variation in methadone plasma levels between patients and within the same patient. Naloxone rapidly disappears from the serum in man and the initial distribution phase has a half-life of 4 minutes. The half-life of naloxone in serum following distribution is 64 minutes. Based on animal studies, the rapid onset of the narcotic antagonist action of naloxone can be related to its rapid entry into the brain, whereas its potency stems in part from its high lipid solubility which allows a high brain concentration to be achieved. The short duration of action of naloxone may result from its rapid egress from the brain.", "contents": "The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. This review illustrates current approaches to the study of the disposition in man of the strong analagesics morphine and methadone and the narcotic antagonist naloxone. Morphine administered orally is rapidly absorbed but equally rapidly metabolised to morphine glucuronide. This contributes to the diminished oral efficacy of morphine. Following intramuscular administration morphine is very rapidly absorbed. After intravenous injection, the serum levels of morphine during the first 10 minutes are higher and more variable in older patients. The half-life of morphine between 20 minutes and 6 hours is 2 to 3 hours and this value does not appear to be influenced by the age of the patient. Similar half-lives for morphine have been reported to normal volunteers and in anaethetised patients who received morphine. Thus, surgical anaesthesia may not markedly influence morphine half-life and disposition. Based on urinary excretion data in man, accelerated morphine metabolism and excretion do not contribute to morphine tolerance. Methadone is now widely used in the treatment of narcotic abuse. The half-life of methadone averages 25 hours. The prolonged retention of methadone in the plasma may be related to its extensive binding to plasma proteins. With chronic dosing, studies in both animals and man indicate an increase in the metabolism of methadone. Unlike morphine, the urinary excretion of methadone increases with acidification of the urine. Women may metabolise methadone to a greater extent than do men. With the exception of pupillary effects, the plasma levels of methadone correlate poorly with its pharmacological activity. There is a marked variation in methadone plasma levels between patients and within the same patient. Naloxone rapidly disappears from the serum in man and the initial distribution phase has a half-life of 4 minutes. The half-life of naloxone in serum following distribution is 64 minutes. Based on animal studies, the rapid onset of the narcotic antagonist action of naloxone can be related to its rapid entry into the brain, whereas its potency stems in part from its high lipid solubility which allows a high brain concentration to be achieved. The short duration of action of naloxone may result from its rapid egress from the brain."}
{"id": "PMID:13958", "title": "Clinical pharmacokinetics of beta-adrenoreceptor blocking drugs.", "content": "All beta-adrenoreceptor blocking drugs seem to be fairly rapidly and completely absorbed from the gastro-intestinal tract. The rate of absorption, however, appears to be lower in elderly patients and possibly also in patients with renal failure than in younger patients. The extent of bioavailability varies considerably between different beta-blockers. Some of these drugs(e.g. alprenolol and propranolol) have a low extent of bioavailability due to a high first-pass elimination effect, while pindolol and practolol for example are in influenced very little by this effect. However, as some beta-blockers from active metabolites, the bioavailability calculated as the ratio between the area under the plasma concentration time curve of unchanged drug after oral and intravenous administration does not give an accurate estimation of the fraction of the biologically active dose reaching the systemic circulation. The beta-blockers so far studied are rapidly distributed in the body. The t1/2 of distribution ranges between 5 to 30 minutes. The apparent volume of distribution varies 3- to 4-fold between the compounds but in all cases the apparent volume of distribution exceeds the physiological body space. In patients with impaired liver function an increase of the volume of distrubution of propranolol has been found. The beta-blockers are relatively rapidly eliminated from the body and most of them have an elimination half-life between 2 to 4 hours. For atenolol, practolol and sotalol higher values have been reported. The most lipophilic beta-blockers are almost completely metabolised in the liver, wheras those of lower lipophilicity are mainly excreted via the kidneys. Impraired liver and kidney function have been found to significantly influence the rate of elimination of those beta-blockers eliminated via the insufficient organ of elimination. Numerous investigators have shown that the beta-blocking effect is linearly related to the logarithm of the plasma concentration. In spite of this relationship, it is difficult from mean data to predict the individual plasma concentration which is necessary for a certain degree of beta-blockade. This might be due to variations in the quantitative formation of active metablolites, individual differences in the plasma protein binding and rather flat plasma level-response curves. Also with respect to the therapeutic effect, the plasma levels vary considerably between individuals. This limits the value of determination of plasma concentrations in order to adjust the therapeutic dose. Our recommendation is that these facilities should be utilised in selected patient groups, eg. those who have a poor therapeutic response to a beta-blocker although the dose is high, and those patient with impaired renal or liver function. The duration of beta-blockade is dose-dependent since the pharmacological effect declines with a constant rate (zero-order kinetics) within relatively wide dosage intervals...", "contents": "Clinical pharmacokinetics of beta-adrenoreceptor blocking drugs. All beta-adrenoreceptor blocking drugs seem to be fairly rapidly and completely absorbed from the gastro-intestinal tract. The rate of absorption, however, appears to be lower in elderly patients and possibly also in patients with renal failure than in younger patients. The extent of bioavailability varies considerably between different beta-blockers. Some of these drugs(e.g. alprenolol and propranolol) have a low extent of bioavailability due to a high first-pass elimination effect, while pindolol and practolol for example are in influenced very little by this effect. However, as some beta-blockers from active metabolites, the bioavailability calculated as the ratio between the area under the plasma concentration time curve of unchanged drug after oral and intravenous administration does not give an accurate estimation of the fraction of the biologically active dose reaching the systemic circulation. The beta-blockers so far studied are rapidly distributed in the body. The t1/2 of distribution ranges between 5 to 30 minutes. The apparent volume of distribution varies 3- to 4-fold between the compounds but in all cases the apparent volume of distribution exceeds the physiological body space. In patients with impaired liver function an increase of the volume of distrubution of propranolol has been found. The beta-blockers are relatively rapidly eliminated from the body and most of them have an elimination half-life between 2 to 4 hours. For atenolol, practolol and sotalol higher values have been reported. The most lipophilic beta-blockers are almost completely metabolised in the liver, wheras those of lower lipophilicity are mainly excreted via the kidneys. Impraired liver and kidney function have been found to significantly influence the rate of elimination of those beta-blockers eliminated via the insufficient organ of elimination. Numerous investigators have shown that the beta-blocking effect is linearly related to the logarithm of the plasma concentration. In spite of this relationship, it is difficult from mean data to predict the individual plasma concentration which is necessary for a certain degree of beta-blockade. This might be due to variations in the quantitative formation of active metablolites, individual differences in the plasma protein binding and rather flat plasma level-response curves. Also with respect to the therapeutic effect, the plasma levels vary considerably between individuals. This limits the value of determination of plasma concentrations in order to adjust the therapeutic dose. Our recommendation is that these facilities should be utilised in selected patient groups, eg. those who have a poor therapeutic response to a beta-blocker although the dose is high, and those patient with impaired renal or liver function. The duration of beta-blockade is dose-dependent since the pharmacological effect declines with a constant rate (zero-order kinetics) within relatively wide dosage intervals..."}
{"id": "PMID:13959", "title": "Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine.", "content": "The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawn from the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite.", "contents": "Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine. The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawn from the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite."}
{"id": "PMID:13960", "title": "Clinical pharmacokinetics of lorazepam. II. Intramuscular injection.", "content": "A single dose of 4 mg of lorazepam was injected into the deltoid muscles of six healthy male volunteers. Multiple venous blood samples were drawn during 48 hr after the dose and all urine was collected for 24 hr after the dose. Concentrations of lorazepam and its major metabolite, lorazepam glucuronide, were determined by electron-capture gas-liquid chromatography. Lorazepam was rapidly absorbed from the injection site, reaching peak concentrations within 3 hr. Mean pharmacokinetic pamrameters for unchanged lorazepam were: apparent absorption half-life: 21.2 min; elimination half-life: 13.6 hr; volume of distribution: 0.9 L/kg; total clearance: 58.2 ml/min. Lorazepam glucuronide rapidly appeared in plasma, reached peak concentrations within 12 hr of the dose, then was eliminated approximately in parallel with the parent drug. Within 24 hr a mean of 47.6% of the dose was recovered in the urine as lorazepam glucuronide and less than 0.5% was recovered as unchanged lorazepam.", "contents": "Clinical pharmacokinetics of lorazepam. II. Intramuscular injection. A single dose of 4 mg of lorazepam was injected into the deltoid muscles of six healthy male volunteers. Multiple venous blood samples were drawn during 48 hr after the dose and all urine was collected for 24 hr after the dose. Concentrations of lorazepam and its major metabolite, lorazepam glucuronide, were determined by electron-capture gas-liquid chromatography. Lorazepam was rapidly absorbed from the injection site, reaching peak concentrations within 3 hr. Mean pharmacokinetic pamrameters for unchanged lorazepam were: apparent absorption half-life: 21.2 min; elimination half-life: 13.6 hr; volume of distribution: 0.9 L/kg; total clearance: 58.2 ml/min. Lorazepam glucuronide rapidly appeared in plasma, reached peak concentrations within 12 hr of the dose, then was eliminated approximately in parallel with the parent drug. Within 24 hr a mean of 47.6% of the dose was recovered in the urine as lorazepam glucuronide and less than 0.5% was recovered as unchanged lorazepam."}
{"id": "PMID:13961", "title": "Toxicity of high-dose flurazepam in the elderly.", "content": "To assess the potential hazards of flurazepam (Dalmane) therapy of insomnia in the elderly, the relation of dosage and patient age to the frequency of flurazepam-attributed adverse reactions was studied in 2,542 hospitalized medical patients. Adverse reactions, predominantly unwanted residual drowsiness, were reported in 78 flurazepam recipients (3.1%). None of the adverse reactions were serious. The frequency of reported toxicity increased with average daily dose, ranging from 1.3% among those receiving less than 15 mg/day to 12.3% at doses of 30 mg/day or more (p less than 0.001). Toxicity increased with age, progressively from 1.9% among those under 60 to 7.1% among those 80 or over (p less than 0.001). Unwanted effects of high-dose flurazepam were observed much more commonly in the elderly. Only 2.0% of those 70 years of age or older experienced adverse reactions at doses under 15 mg/day, as opposed to 39.0% at 30 mg or more per day. Low doses of flurazepam appear to be safe for elderly individuals, but they are susceptible to unwanted central nervous system depression at high doses.", "contents": "Toxicity of high-dose flurazepam in the elderly. To assess the potential hazards of flurazepam (Dalmane) therapy of insomnia in the elderly, the relation of dosage and patient age to the frequency of flurazepam-attributed adverse reactions was studied in 2,542 hospitalized medical patients. Adverse reactions, predominantly unwanted residual drowsiness, were reported in 78 flurazepam recipients (3.1%). None of the adverse reactions were serious. The frequency of reported toxicity increased with average daily dose, ranging from 1.3% among those receiving less than 15 mg/day to 12.3% at doses of 30 mg/day or more (p less than 0.001). Toxicity increased with age, progressively from 1.9% among those under 60 to 7.1% among those 80 or over (p less than 0.001). Unwanted effects of high-dose flurazepam were observed much more commonly in the elderly. Only 2.0% of those 70 years of age or older experienced adverse reactions at doses under 15 mg/day, as opposed to 39.0% at 30 mg or more per day. Low doses of flurazepam appear to be safe for elderly individuals, but they are susceptible to unwanted central nervous system depression at high doses."}
{"id": "PMID:13962", "title": "Quantitative immunological determination of brush-border protein in urine. Their role in the progression of inflammatory and toxic renal damage.", "content": "In urine concentrates form patients with acute and chronic glomerulonephritis and patients under cytostatic treatment, remarkable amounts of membrane-bound alanine-aminopeptidase, alkaline-phosphatase and gamma-glutamyltraspeptidase could be recognized. With an anti-brush-border antisera membrane-bound enzymes could be differentiated from soluble fractions of other origins. Patients with recognizable membrane proteins in urine showed tendencies toward progression of their kidney diseases. Patients under cytostatic treatment with high dose showed a very early output of these enzymes while others under low dose started after a longer treatment with the excretion of membrane-bound enzymes.", "contents": "Quantitative immunological determination of brush-border protein in urine. Their role in the progression of inflammatory and toxic renal damage. In urine concentrates form patients with acute and chronic glomerulonephritis and patients under cytostatic treatment, remarkable amounts of membrane-bound alanine-aminopeptidase, alkaline-phosphatase and gamma-glutamyltraspeptidase could be recognized. With an anti-brush-border antisera membrane-bound enzymes could be differentiated from soluble fractions of other origins. Patients with recognizable membrane proteins in urine showed tendencies toward progression of their kidney diseases. Patients under cytostatic treatment with high dose showed a very early output of these enzymes while others under low dose started after a longer treatment with the excretion of membrane-bound enzymes."}
{"id": "PMID:13963", "title": "Measurement of carbon dioxide in blood.", "content": "The remarkable combination of physical and chemical properties displayed by carbon dioxide has enabled the development of a very wide variety of analytical methods for its measurement in blood or blood plasma. Both for historical and technical reasons, the gasometric method of Van Slyke and Neill is preeminent, but great skill is needed to realize its full precision and accuracy. The microgasometer of Natelson, however, has served the clinical laboratory well as a practicable manual means of microanalysis for total carbon dioxide. So far as automated analysis is concerned, it is highly significant that one of the first applications of Skegg's continuous flow principle was to the titrimetric determination of total carbon dioxide in serum; the AutoAnalyzer technique remains the most widely used of its kind, in spite of inherent difficulties in specimen handling, instrumental standardization, and quality control. At the same time, it has been pointed out that the routine determination of total carbon dioxide in serum does not offer a useful screening procedure for identifying or characterizing patients with acid-base disorders; full assessment of acid-base status, including pCO2 in selected patients is much more rewarding. The credit for bringing pCO2 measurements within the scope of the clinical laboratory, by means of the interpolation technique, is largely due to Astrup and his colleagues. Nevertheless, continual improvements have been made in the design and performance of the Severinghaus type of pCO2 electrode, so that reliable instruments offering direct readout of blood pCO2 are available from several manufacturers. The more elaborate versions of these instruments are rugged and work-simplified, and they offer automated self-calibration and end-point detection for pH and pO2, as well as pCO2. It will be surprising if such instruments do not come into widespread use.", "contents": "Measurement of carbon dioxide in blood. The remarkable combination of physical and chemical properties displayed by carbon dioxide has enabled the development of a very wide variety of analytical methods for its measurement in blood or blood plasma. Both for historical and technical reasons, the gasometric method of Van Slyke and Neill is preeminent, but great skill is needed to realize its full precision and accuracy. The microgasometer of Natelson, however, has served the clinical laboratory well as a practicable manual means of microanalysis for total carbon dioxide. So far as automated analysis is concerned, it is highly significant that one of the first applications of Skegg's continuous flow principle was to the titrimetric determination of total carbon dioxide in serum; the AutoAnalyzer technique remains the most widely used of its kind, in spite of inherent difficulties in specimen handling, instrumental standardization, and quality control. At the same time, it has been pointed out that the routine determination of total carbon dioxide in serum does not offer a useful screening procedure for identifying or characterizing patients with acid-base disorders; full assessment of acid-base status, including pCO2 in selected patients is much more rewarding. The credit for bringing pCO2 measurements within the scope of the clinical laboratory, by means of the interpolation technique, is largely due to Astrup and his colleagues. Nevertheless, continual improvements have been made in the design and performance of the Severinghaus type of pCO2 electrode, so that reliable instruments offering direct readout of blood pCO2 are available from several manufacturers. The more elaborate versions of these instruments are rugged and work-simplified, and they offer automated self-calibration and end-point detection for pH and pO2, as well as pCO2. It will be surprising if such instruments do not come into widespread use."}
{"id": "PMID:13964", "title": "Treatment of asthma with theophylline and beta adrenergic agents.", "content": "The understanding of the properties of adrenergic receptors and modification of ring and the N-alkyl side chain constituents have resulted in adrenergic agents with a high degree of specificity for the lung and few cardiac and central nervous system stimulating problems. These agents are useful by aerosol and oral routes, alone and in addition to theophylline for asthma. Theophylline, which acts to increase cyclic AMP by inhibition of phosphodiesterase and beta 2 adrenergic agents which increase cyclic AMP by stimulating adenylate cyclase, are the mainstays of asthma therapy. Therapy is usually begun with theophylline. Persistent symptoms with adequate theophylline levels (10-20 mug/ml) indicates the need for a beta 2 adrenergic agent by aerosol or orally as a supplement. Occasional patients will not tolerate theophylline in any preparation and can be treated with beta 2 adrenergic agents with success. The future holds great promise for improved and safer beta 2 adrenergic agents which will offer the physician a more effective means of treating asthma.", "contents": "Treatment of asthma with theophylline and beta adrenergic agents. The understanding of the properties of adrenergic receptors and modification of ring and the N-alkyl side chain constituents have resulted in adrenergic agents with a high degree of specificity for the lung and few cardiac and central nervous system stimulating problems. These agents are useful by aerosol and oral routes, alone and in addition to theophylline for asthma. Theophylline, which acts to increase cyclic AMP by inhibition of phosphodiesterase and beta 2 adrenergic agents which increase cyclic AMP by stimulating adenylate cyclase, are the mainstays of asthma therapy. Therapy is usually begun with theophylline. Persistent symptoms with adequate theophylline levels (10-20 mug/ml) indicates the need for a beta 2 adrenergic agent by aerosol or orally as a supplement. Occasional patients will not tolerate theophylline in any preparation and can be treated with beta 2 adrenergic agents with success. The future holds great promise for improved and safer beta 2 adrenergic agents which will offer the physician a more effective means of treating asthma."}
{"id": "PMID:13967", "title": "An in vitro investigation of barium meals.", "content": "A technique is described for the in vitro study of the interaction of barium sulphate suspensions, used as radiopaques, with rat ileum. The technique, which allows close approximation to the in vivo situation with accurate control of the experimental conditions, was shown to give reproducible results. The thickness of the radiopaque retained at the gut surface was related to the concentration of the suspension, but was not significantly affected by the pH of the suspension. Less viscous suspensions gave better coating of the gut surface. The nature of the stabilizing agent or the surface charge carried by the particles does not affect the adhesion of the particles to the ileal mucus.", "contents": "An in vitro investigation of barium meals. A technique is described for the in vitro study of the interaction of barium sulphate suspensions, used as radiopaques, with rat ileum. The technique, which allows close approximation to the in vivo situation with accurate control of the experimental conditions, was shown to give reproducible results. The thickness of the radiopaque retained at the gut surface was related to the concentration of the suspension, but was not significantly affected by the pH of the suspension. Less viscous suspensions gave better coating of the gut surface. The nature of the stabilizing agent or the surface charge carried by the particles does not affect the adhesion of the particles to the ileal mucus."}
{"id": "PMID:13968", "title": "Effect of ultrasonic nebulization on arterial oxygen saturation in chronic obstructive pulmonary disease.", "content": "Twenty patients with mild to severe chronic obstructive pulmonary disease received ultrasonic nebulization to assess the danger of short-term changes in blood gas levels during this therapy. The status of arterial oxygenation was monitored during 20 minutes of therapy and for 20 minutes following therapy. In nine patients with periodic studies of arterial blood, the mean change in arterial oxygen pressure from base line was a decrease of 0.8 mm Hg at ten minutes into therapy, 2.8 mm Hg at the conclusion of therapy, and 2.9 mm Hg 20 minutes after therapy. In all 20 patients, ear oximetric studies showed only a small mean change at ten minutes into therapy, at the end of therapy, and at 20 minutes after therapy. Changes in the status of arterial oxygenation during and after therapy with ultrasonic nebulization in a group of patients with chronic obstructive pulmonary disease are generally small and of no statistical and limited clinical significance; however, alarming falls in arterial oxygenation can occur and cannot be predicted by base-line testing of pulmonary function or studies of arterial blood. It would be prudent to monitor patients with chronic obstructive pulmonary disease during therapy with ultrasonic nebulization or to withhold therapy altogether.", "contents": "Effect of ultrasonic nebulization on arterial oxygen saturation in chronic obstructive pulmonary disease. Twenty patients with mild to severe chronic obstructive pulmonary disease received ultrasonic nebulization to assess the danger of short-term changes in blood gas levels during this therapy. The status of arterial oxygenation was monitored during 20 minutes of therapy and for 20 minutes following therapy. In nine patients with periodic studies of arterial blood, the mean change in arterial oxygen pressure from base line was a decrease of 0.8 mm Hg at ten minutes into therapy, 2.8 mm Hg at the conclusion of therapy, and 2.9 mm Hg 20 minutes after therapy. In all 20 patients, ear oximetric studies showed only a small mean change at ten minutes into therapy, at the end of therapy, and at 20 minutes after therapy. Changes in the status of arterial oxygenation during and after therapy with ultrasonic nebulization in a group of patients with chronic obstructive pulmonary disease are generally small and of no statistical and limited clinical significance; however, alarming falls in arterial oxygenation can occur and cannot be predicted by base-line testing of pulmonary function or studies of arterial blood. It would be prudent to monitor patients with chronic obstructive pulmonary disease during therapy with ultrasonic nebulization or to withhold therapy altogether."}
{"id": "PMID:13969", "title": "Controlled comparison of bromazepam, amitriptyline, and placebo in anxiety-depressive neurosis.", "content": "Seventy-two private practice patients with moderate or severe anxiety-depressive neurosis received mean daily oral doses of 23.8 mg bromazepam, 94 mg amitriptyline, or 4.6 capsules of placebo in a double-blind four-week study. The patient's condition was assessed initially and  at weekly intervals by using the Brief Psychiatric Rating Scale and the Hamilton Psychiatric Rating Scale for Depression. From the first through the fourth week evaluations, a larger proportion of patients improved on bromazepam than on amitriptyline. Bromazepam was also superior to amitriptyline and placebo in the degree of improvement made Statistical significance (p less than 0.05) of the changes noted after one week was even greater after four weeks, particularly in BPRS items of somatic concern, depressive mood, anxiety and tension and in nearly all representative psychic and somatic symptoms on the depression scale, confirmed by global evaluation. Compared to bromazepam patients, amitriptyline patients had significantly severer adverse reactions which were the major cause of the group's higher dropout rate (66% vs 33%). The prompt clinical response to bromazepam contributed to its superior safety and patient progress in that it was possible to carefully titrate dosage and thus help to control adverse reactions and allow patients to maintain alertness and productivity under therapy.", "contents": "Controlled comparison of bromazepam, amitriptyline, and placebo in anxiety-depressive neurosis. Seventy-two private practice patients with moderate or severe anxiety-depressive neurosis received mean daily oral doses of 23.8 mg bromazepam, 94 mg amitriptyline, or 4.6 capsules of placebo in a double-blind four-week study. The patient's condition was assessed initially and  at weekly intervals by using the Brief Psychiatric Rating Scale and the Hamilton Psychiatric Rating Scale for Depression. From the first through the fourth week evaluations, a larger proportion of patients improved on bromazepam than on amitriptyline. Bromazepam was also superior to amitriptyline and placebo in the degree of improvement made Statistical significance (p less than 0.05) of the changes noted after one week was even greater after four weeks, particularly in BPRS items of somatic concern, depressive mood, anxiety and tension and in nearly all representative psychic and somatic symptoms on the depression scale, confirmed by global evaluation. Compared to bromazepam patients, amitriptyline patients had significantly severer adverse reactions which were the major cause of the group's higher dropout rate (66% vs 33%). The prompt clinical response to bromazepam contributed to its superior safety and patient progress in that it was possible to carefully titrate dosage and thus help to control adverse reactions and allow patients to maintain alertness and productivity under therapy."}
{"id": "PMID:13970", "title": "Characteristics of a microsomal cytochrome P-448-mediated reaction. Ethoxyresorufin O-de-ethylation.", "content": "Certain characteristics of ethoxyresorufin O-de-ethylation, as catalyzed by microsomes of liver, lung, and intestine of control and pretreated rats and hamsters, were studied. The results support previous suggestions that the reaction is catalyzed primarily by a 3-methyl-cholanthrene (MC)-inducible mono-oxygenase which has a 448-nm absorption maximum in the reduced-CO difference spectrum. Ethoxyresorufin exhibited a type I binding spectrum with liver microsomes from MC-induced rats, but there was no clear interaction with microsomes from control or phenobarbital (PB)-induced rats. Maximum MC-induction of type I binding and de-ethylase activity coincided with the appearance of a cytochrome P-450 spectrum whose absorption maximum was shifted to 448 nm. Low concentrations of alpha-naphthoflavone (ANF) or benzo[a]pyrene (BP) inhibited the de-ethylation with liver microsomes of MC-treated rats (150 approximately 10(-9)M) but not those of control rats. A kinetic analysis of BP inhibition of this reaction showed it to be competitive. Inhibition of the MC-induced liver microsomal reaction by low concentrations of BP or ANF diminished rapidly with time. MC-induced rat liver microsomal de-ethylation of ethoxyresorufin was less sensitive than the PB-induced reaction to inhibition by metyrapone or SKF 525-A (I50 approximately 10(-6) - 10(-4)M). However, microsomes from rat liver, lung, and intestine had very low constitutive activities (less than 0.1 nmol/min/mg of protein). MC greatly induced the de-ethylation reaction in liver (200 X), intestine (40 X) and lung (10 X). De-ethylation of ethoxyresorufin in microsomes from control and MC-induced rat lung was inhibited by low concentrations of either ANF or BP (I50 approximately 10(-8) M). Control hamster liver microsomes were several times more active in de-ethylation than control rat liver microsomes, but MC-induction of hamster liver was only 1/10 of that in rat liver. Control hamster lung activity was similar to that of control rat lung, but was not appreciably induced by MC.", "contents": "Characteristics of a microsomal cytochrome P-448-mediated reaction. Ethoxyresorufin O-de-ethylation. Certain characteristics of ethoxyresorufin O-de-ethylation, as catalyzed by microsomes of liver, lung, and intestine of control and pretreated rats and hamsters, were studied. The results support previous suggestions that the reaction is catalyzed primarily by a 3-methyl-cholanthrene (MC)-inducible mono-oxygenase which has a 448-nm absorption maximum in the reduced-CO difference spectrum. Ethoxyresorufin exhibited a type I binding spectrum with liver microsomes from MC-induced rats, but there was no clear interaction with microsomes from control or phenobarbital (PB)-induced rats. Maximum MC-induction of type I binding and de-ethylase activity coincided with the appearance of a cytochrome P-450 spectrum whose absorption maximum was shifted to 448 nm. Low concentrations of alpha-naphthoflavone (ANF) or benzo[a]pyrene (BP) inhibited the de-ethylation with liver microsomes of MC-treated rats (150 approximately 10(-9)M) but not those of control rats. A kinetic analysis of BP inhibition of this reaction showed it to be competitive. Inhibition of the MC-induced liver microsomal reaction by low concentrations of BP or ANF diminished rapidly with time. MC-induced rat liver microsomal de-ethylation of ethoxyresorufin was less sensitive than the PB-induced reaction to inhibition by metyrapone or SKF 525-A (I50 approximately 10(-6) - 10(-4)M). However, microsomes from rat liver, lung, and intestine had very low constitutive activities (less than 0.1 nmol/min/mg of protein). MC greatly induced the de-ethylation reaction in liver (200 X), intestine (40 X) and lung (10 X). De-ethylation of ethoxyresorufin in microsomes from control and MC-induced rat lung was inhibited by low concentrations of either ANF or BP (I50 approximately 10(-8) M). Control hamster liver microsomes were several times more active in de-ethylation than control rat liver microsomes, but MC-induction of hamster liver was only 1/10 of that in rat liver. Control hamster lung activity was similar to that of control rat lung, but was not appreciably induced by MC."}
{"id": "PMID:13971", "title": "Microsomal glucuronidation of a quaternary ammonium compound, 3-hydroxyphenyltrimethylammonium.", "content": "3-Hydroxyphenyltrimethylammonium (HPTMA) is glucuronidated in vitro by rat liver microsomes supplemented with UDP-glucuronic acid. Little reaction occurred in the postmicrosomal supernatant fraction. Triton X-100 doubled the maximal velocity for the microsomecatalyzed reaction without altering the apparent KM value for HPTMA. This is the first report of glucuronidation of a quaternary ammonium compound in vitro.", "contents": "Microsomal glucuronidation of a quaternary ammonium compound, 3-hydroxyphenyltrimethylammonium. 3-Hydroxyphenyltrimethylammonium (HPTMA) is glucuronidated in vitro by rat liver microsomes supplemented with UDP-glucuronic acid. Little reaction occurred in the postmicrosomal supernatant fraction. Triton X-100 doubled the maximal velocity for the microsomecatalyzed reaction without altering the apparent KM value for HPTMA. This is the first report of glucuronidation of a quaternary ammonium compound in vitro."}
{"id": "PMID:13972", "title": "The perinatal development of epoxide-metabolizing enzyme activities in liver and extrahepatic organs of guinea pig and rabbit.", "content": "We have measured the activities of epoxide hydrase in microsomes and glutathione S-epoxidetransferase and glutathione S-aryltransferase in cytosol fractions of liver, lungs, kidneys, and small intestine from fetal and neonatal guinea pigs and rabbits. The rates at which adult values of these enzyme activities are reached in extrahepatic tissues differ from the rates of maturation of the hepatic enzyme activities for both species. In addition, the two pathways of epoxide metabolism studied here developed with age at different rates in any one organ. However, both cytosol glutathione S-transferases showed very similar developmental profiles in any one organ. It was especially interesting that the activities of both glutathione S-transferases were within the adult range in pulmonary cytosol fraction of guinea pig and rabbit before birth. Intestinal microsomes did not have adult values for epoxide hydrase activity until several weeks after birth. A feature common to both epoxide-metabolizing activities in hepatic and extrahepatic organs was a drop in mean specific activity, sometimes not statistically significant, around the time of birth. This decrease appeared to be due to dilution of the active enzyme with other protein, inasmuch as the total organ activity, in general, showed no such decline. We found that the pattern of development of hepatic microsomal epoxide hydrase activity was similar to developmental patterns published by others for hepatic microsomal mixed-function oxidases, and also that development of hepatic cytosol glutathione S-transferase was similar to hepatic development of glutathione S-transferase towards other substrates described in the literature.", "contents": "The perinatal development of epoxide-metabolizing enzyme activities in liver and extrahepatic organs of guinea pig and rabbit. We have measured the activities of epoxide hydrase in microsomes and glutathione S-epoxidetransferase and glutathione S-aryltransferase in cytosol fractions of liver, lungs, kidneys, and small intestine from fetal and neonatal guinea pigs and rabbits. The rates at which adult values of these enzyme activities are reached in extrahepatic tissues differ from the rates of maturation of the hepatic enzyme activities for both species. In addition, the two pathways of epoxide metabolism studied here developed with age at different rates in any one organ. However, both cytosol glutathione S-transferases showed very similar developmental profiles in any one organ. It was especially interesting that the activities of both glutathione S-transferases were within the adult range in pulmonary cytosol fraction of guinea pig and rabbit before birth. Intestinal microsomes did not have adult values for epoxide hydrase activity until several weeks after birth. A feature common to both epoxide-metabolizing activities in hepatic and extrahepatic organs was a drop in mean specific activity, sometimes not statistically significant, around the time of birth. This decrease appeared to be due to dilution of the active enzyme with other protein, inasmuch as the total organ activity, in general, showed no such decline. We found that the pattern of development of hepatic microsomal epoxide hydrase activity was similar to developmental patterns published by others for hepatic microsomal mixed-function oxidases, and also that development of hepatic cytosol glutathione S-transferase was similar to hepatic development of glutathione S-transferase towards other substrates described in the literature."}
{"id": "PMID:13973", "title": "Metabolism of di-2-ethylhexyl phthalate by subcellular fractions from rainbow trout liver.", "content": "Trout liver homogenates metabolized di-2-ethylhexyl phthalate (DEHP) to monoethylhexyl phthalate (MEHP) without added NADPH and to MEHP and more polar metabolites with added NADPH. Both hydrolysis and oxidative metabolism of DEHP were inhibited by piperonyl butoxide. The 10,000g pellet, 100,000g pellet and 100,000g supernatant fraction from liver homogenates all catalyzed the hydrolysis of DEHP and all but the 100,000g supernatant fraction showed the shift to more polar metabolites with added NADPH; serum also catalyzed the hydrolysis of DEHP. Measurement of the microsomal marker, glucose 6-phosphatase, and the mitochondrial marker, succinic dehydrogenase, revealed that DEHP-hydrolytic activity was associated with microsomes and the 100,000g supernatant fraction, whereas DEHP oxidation was associated only with microsomes.", "contents": "Metabolism of di-2-ethylhexyl phthalate by subcellular fractions from rainbow trout liver. Trout liver homogenates metabolized di-2-ethylhexyl phthalate (DEHP) to monoethylhexyl phthalate (MEHP) without added NADPH and to MEHP and more polar metabolites with added NADPH. Both hydrolysis and oxidative metabolism of DEHP were inhibited by piperonyl butoxide. The 10,000g pellet, 100,000g pellet and 100,000g supernatant fraction from liver homogenates all catalyzed the hydrolysis of DEHP and all but the 100,000g supernatant fraction showed the shift to more polar metabolites with added NADPH; serum also catalyzed the hydrolysis of DEHP. Measurement of the microsomal marker, glucose 6-phosphatase, and the mitochondrial marker, succinic dehydrogenase, revealed that DEHP-hydrolytic activity was associated with microsomes and the 100,000g supernatant fraction, whereas DEHP oxidation was associated only with microsomes."}
{"id": "PMID:13974", "title": "Biotransformation of D(-)-ephedrine and L(+)-ephedrine in the rabbit, in vivo and in vitro.", "content": "Investigations were carried out with radiolabeled D(-)-ephedrine and L(+)-ephedrine to establish whether differences exist in their metabolic fate in the rabbit, in vivo and in vitro. In liver microsomal preparations, a) D(-)-ephedrine was metabolized at a faster rate than L(+)-ephedrine, b) benzoic acid was formed from D(-)ephedrine at a rate about three times greater than from the L(+)-isomer, and c) the relative amounts of norephedrine and 1-phenyl-1,2-propranediol formed from both ephedrine isomers were nearly identical throughout the entire incubation period. In vivo, both ephedrine isomers were extensively metabolized and the majority of total radioactivity (71-91%) was excreted within 24 hr. A greater 14C-excretion rate was observed for L(+)-ephedrine. From an analysis of 0- to 24-hr urine, it was found that a) 47-50% of the urinary 14C was attributable to acidic metabolites (hippuric acid and benzoic acid) from L(+)- and D(-)-ephedrine, b) from 4 to 16% of the total 14C obtained with both isomers was accountable as 1-phenyl-1,2-propanediol, either free or as a glucuronide conjugate, c) no appreciable quantities of sulfate or glucuronide conjugates of p-hydroxylated metabolites of ephedrine or norephedrine was detectable, and d) small amounts (less than 4% of metabolites corresponding to unchanged ephedrine, norephedrine, or 1-hydroxy-1-phenyl-2-propanone were found in urine of animals given either isomer. These experiments indicate that the major pathway for the biotransformation of D(-)-ephedrine and L(+)-ephedrine involves N-demethylation and oxidative deamination of the side chain.", "contents": "Biotransformation of D(-)-ephedrine and L(+)-ephedrine in the rabbit, in vivo and in vitro. Investigations were carried out with radiolabeled D(-)-ephedrine and L(+)-ephedrine to establish whether differences exist in their metabolic fate in the rabbit, in vivo and in vitro. In liver microsomal preparations, a) D(-)-ephedrine was metabolized at a faster rate than L(+)-ephedrine, b) benzoic acid was formed from D(-)ephedrine at a rate about three times greater than from the L(+)-isomer, and c) the relative amounts of norephedrine and 1-phenyl-1,2-propranediol formed from both ephedrine isomers were nearly identical throughout the entire incubation period. In vivo, both ephedrine isomers were extensively metabolized and the majority of total radioactivity (71-91%) was excreted within 24 hr. A greater 14C-excretion rate was observed for L(+)-ephedrine. From an analysis of 0- to 24-hr urine, it was found that a) 47-50% of the urinary 14C was attributable to acidic metabolites (hippuric acid and benzoic acid) from L(+)- and D(-)-ephedrine, b) from 4 to 16% of the total 14C obtained with both isomers was accountable as 1-phenyl-1,2-propanediol, either free or as a glucuronide conjugate, c) no appreciable quantities of sulfate or glucuronide conjugates of p-hydroxylated metabolites of ephedrine or norephedrine was detectable, and d) small amounts (less than 4% of metabolites corresponding to unchanged ephedrine, norephedrine, or 1-hydroxy-1-phenyl-2-propanone were found in urine of animals given either isomer. These experiments indicate that the major pathway for the biotransformation of D(-)-ephedrine and L(+)-ephedrine involves N-demethylation and oxidative deamination of the side chain."}
{"id": "PMID:13975", "title": "Identification of glucuronide metabolites of benzomorphan narcotic analgesic drugs in bile from the isolated perfused rat liver by gas chromatography and mass spectrometry.", "content": "The metabolism of four benzomorphan compounds was studied in the isolated perfused rat liver, and glucuronide metabolites were identified by combined gas chromatography-mass spectrometry (GC/MS). Cyclazocine, ketocyclazocine, volazocine, and pantazocine were each added to the perfusate of the isolated perfused rat liver and the bile collected for 3 hours. The residue from evaporation of the bile was derivatized with the dimethylsulfoxide anion and methyl iodide, and the permethylated glucuronide metabolites were identified by GC/MS. The four compounds were hydroxylated by the liver and excreted in the bile as phenolic glucuronides. For example, permethylated hydroxycyclazocine glucuronide had a mass spectrum with a molecular ion at m/e 533 and fragment ions at m/e 301 (aglycone), m/e 260 (loss of cyclopropyl group) and prominent ions at m/e 232, 201, 169, 141, and 101 caused by fragmentation of the permethylated glucuronic acid moiety. Perdeuteriomethylation demonstrated that pentazocine, volazocine, and cyclazocine were further metabolized by methylation of one hydroxy substituent and glucuronidation on the other. Pentazocine, cyclazocine, and ketocyclazocine were also metabolized to phenolic glucuronides of the parent drugs. N-deakylated metabolites  of pentazocine, volazocine, and cyclazocine were identified both as permethylated glucuronic acid conjugates and as the trimethylsilyl derivatives of the aglycones, obtained by enzymatic hydrolysis on the conjugates in bile.", "contents": "Identification of glucuronide metabolites of benzomorphan narcotic analgesic drugs in bile from the isolated perfused rat liver by gas chromatography and mass spectrometry. The metabolism of four benzomorphan compounds was studied in the isolated perfused rat liver, and glucuronide metabolites were identified by combined gas chromatography-mass spectrometry (GC/MS). Cyclazocine, ketocyclazocine, volazocine, and pantazocine were each added to the perfusate of the isolated perfused rat liver and the bile collected for 3 hours. The residue from evaporation of the bile was derivatized with the dimethylsulfoxide anion and methyl iodide, and the permethylated glucuronide metabolites were identified by GC/MS. The four compounds were hydroxylated by the liver and excreted in the bile as phenolic glucuronides. For example, permethylated hydroxycyclazocine glucuronide had a mass spectrum with a molecular ion at m/e 533 and fragment ions at m/e 301 (aglycone), m/e 260 (loss of cyclopropyl group) and prominent ions at m/e 232, 201, 169, 141, and 101 caused by fragmentation of the permethylated glucuronic acid moiety. Perdeuteriomethylation demonstrated that pentazocine, volazocine, and cyclazocine were further metabolized by methylation of one hydroxy substituent and glucuronidation on the other. Pentazocine, cyclazocine, and ketocyclazocine were also metabolized to phenolic glucuronides of the parent drugs. N-deakylated metabolites  of pentazocine, volazocine, and cyclazocine were identified both as permethylated glucuronic acid conjugates and as the trimethylsilyl derivatives of the aglycones, obtained by enzymatic hydrolysis on the conjugates in bile."}
{"id": "PMID:13976", "title": "Mirex-induced impairment of hepatobiliary function. Suppressed biliary excretion of imipramine and sulfobromophthalein.", "content": "Effect of pre-exposure to the pesticide mirex on hepatic uptake, metabolism, and biliary excretion of the tricyclic antidepressant, imipramine (IMP), was studied by using isolated perfused rat liver preparations obtained from control and treated animals. Pretreatment of male rats with mirex (50 mg/kg/day, po, for 3 days) resulted in a marked suppression (91%) of biliary excretion of endogenously formed polar metabolites of IMP. This impairment of biliary excretory function is related neither to the bile flow nor to the rate of metabolism of IMP. These conclusions are supported by the following observations: 1) pre-exposure to mirex results in a significant increase in bile secretion; 2) endogenously formed metabolites of IMP accumulate in increasing concentrations in the perfusate of liver preparations from mirex-treated rats; 3) over 98% of the IMP was metabolized by livers of both control and mirex-treated rats. Furthermore, biliary excretion of exogenously provided polar metabolites of IMP was also suppressed by 88% of that of control livers. Addition of mirex (5 X 10(-5) M) to the perfusate of control liver preparations was without effect on biliary excretion of IMP metabolites. Biliary excretion of sulfobromophthalein was also markedly suppressed (90%) by preexposure to mirex. These results suggest that mirex-induced impairment of hepatobiliary function is not specific to substrates. The mechanism of mirex-induced impairment is located at the site of transfer of otherwise readily excretable substances such as metabolites of IMP and sulfobromophthalein.", "contents": "Mirex-induced impairment of hepatobiliary function. Suppressed biliary excretion of imipramine and sulfobromophthalein. Effect of pre-exposure to the pesticide mirex on hepatic uptake, metabolism, and biliary excretion of the tricyclic antidepressant, imipramine (IMP), was studied by using isolated perfused rat liver preparations obtained from control and treated animals. Pretreatment of male rats with mirex (50 mg/kg/day, po, for 3 days) resulted in a marked suppression (91%) of biliary excretion of endogenously formed polar metabolites of IMP. This impairment of biliary excretory function is related neither to the bile flow nor to the rate of metabolism of IMP. These conclusions are supported by the following observations: 1) pre-exposure to mirex results in a significant increase in bile secretion; 2) endogenously formed metabolites of IMP accumulate in increasing concentrations in the perfusate of liver preparations from mirex-treated rats; 3) over 98% of the IMP was metabolized by livers of both control and mirex-treated rats. Furthermore, biliary excretion of exogenously provided polar metabolites of IMP was also suppressed by 88% of that of control livers. Addition of mirex (5 X 10(-5) M) to the perfusate of control liver preparations was without effect on biliary excretion of IMP metabolites. Biliary excretion of sulfobromophthalein was also markedly suppressed (90%) by preexposure to mirex. These results suggest that mirex-induced impairment of hepatobiliary function is not specific to substrates. The mechanism of mirex-induced impairment is located at the site of transfer of otherwise readily excretable substances such as metabolites of IMP and sulfobromophthalein."}
{"id": "PMID:13977", "title": "Metabolic fate of phenobarbital. A quantitative study of p-hydroxyphenobarbital elimination in man.", "content": "Biotransformation of phenobarbital (PB) to p-hydroxyphenobarbital (PHPB) was studied quantitatively by gas-liquid chromatography in 8 epileptic patients who were receiving an established regimen of antiepileptic drugs including PB. PB and both conjugated and unconjugated PHPB were present in each patient's urine; m-hydroxyphenobarbital (MHPB) was not detected despite an assay sensitivity of 0.25 mug/ml. Incubation of the urine with beta-glucuronidase, but not with arylsulfatase, liberated PHPB which was, therefore, presumed to be conjugated with glucuronic acid. In general, the patients' urine contained more PB than total PHPB. Recovery of the patients' total daily dose of PB ranged from 24 to 77% (mean, 42%). After receiving a single iv dose of PB, PB and both conjugated and unconjugated PHPB were found in a normal volunteer's urine throughout a 16-day collection period; 30% of the dose was recovered. PB excretion was proportional to urine volume in the volunteer and in two additional patients who were made to vary their daily fluid intake. PHPB was not detected in the cerebrospinal fluid of 10 patients receiving PB. Neither PB, PHPB, nor MHPB were detected in the feces of four patients. These results suggest that metabolites other than PHPB or MHPB may be important in the elimination of PB in man.", "contents": "Metabolic fate of phenobarbital. A quantitative study of p-hydroxyphenobarbital elimination in man. Biotransformation of phenobarbital (PB) to p-hydroxyphenobarbital (PHPB) was studied quantitatively by gas-liquid chromatography in 8 epileptic patients who were receiving an established regimen of antiepileptic drugs including PB. PB and both conjugated and unconjugated PHPB were present in each patient's urine; m-hydroxyphenobarbital (MHPB) was not detected despite an assay sensitivity of 0.25 mug/ml. Incubation of the urine with beta-glucuronidase, but not with arylsulfatase, liberated PHPB which was, therefore, presumed to be conjugated with glucuronic acid. In general, the patients' urine contained more PB than total PHPB. Recovery of the patients' total daily dose of PB ranged from 24 to 77% (mean, 42%). After receiving a single iv dose of PB, PB and both conjugated and unconjugated PHPB were found in a normal volunteer's urine throughout a 16-day collection period; 30% of the dose was recovered. PB excretion was proportional to urine volume in the volunteer and in two additional patients who were made to vary their daily fluid intake. PHPB was not detected in the cerebrospinal fluid of 10 patients receiving PB. Neither PB, PHPB, nor MHPB were detected in the feces of four patients. These results suggest that metabolites other than PHPB or MHPB may be important in the elimination of PB in man."}
{"id": "PMID:13978", "title": "N-Hydroxylation of pentobarbital in man.", "content": "After oral administration of 14C-labeled pentobarbital to healthy subjects, most ot the radioactivity was recovered in urine over a period of 6 days. Only a minute amount (approximately 1%) of unchanged pentobarbital was found in the urine. Four major metabolites were found and isolated. One was 3'-hydroxypentobarbital, which has been previously identified by Maynert. The second could be identified as N-hydroxypentobarbital on the basis of its spectral and chemical properties. The other two metabolites were not identified.", "contents": "N-Hydroxylation of pentobarbital in man. After oral administration of 14C-labeled pentobarbital to healthy subjects, most ot the radioactivity was recovered in urine over a period of 6 days. Only a minute amount (approximately 1%) of unchanged pentobarbital was found in the urine. Four major metabolites were found and isolated. One was 3'-hydroxypentobarbital, which has been previously identified by Maynert. The second could be identified as N-hydroxypentobarbital on the basis of its spectral and chemical properties. The other two metabolites were not identified."}
{"id": "PMID:13983", "title": "Narcotic and narcotic antagonist pKa's and partition coefficients and their significance in clinical practice.", "content": "The pKa's, partition coefficients and drug distribution coefficients (apparent partition coefficients) have been investigated for a number of narcotics and where possible for their congener narcotic antagonist. These studies were carried out by a novel microelectrometric titration technique as a function of temperature and pH. This method enables one to determine not only the dissociation constants to deconvolute overlapping pKa's, but also to determine the solubilities and oil-water distribution of these various drugs. The drug distribution coefficients displayed marked sensitivity to pH at values which span the range of attainable human physiological pH values. This has significant pharmacological implications for proper choice and scaling of drug dosages under various clinical situations among which are cited hyperventilation under a general anesthetic while concomitantly under a narcotic analgesic, obstetetrical analgesia, and medical and anti-abuse usage of narcotic antagonists. The partition coefficients and drug distribution coefficients were noticeably different at 20degreesC (where such measurements are customarily made) from those at 37degreesC (body temperature). Furthermore, various drugs exhibit very non-equivalent increases in drug distribution coefficients with increasing temperature, ranging from 21% for naltrexone. This non-regularity indicates that it will not be valid to extrapolate by any constant factor the measurements made at lower temperatures. Even the true partition coefficients increase with temperature from 20degrees to 37degreesC.", "contents": "Narcotic and narcotic antagonist pKa's and partition coefficients and their significance in clinical practice. The pKa's, partition coefficients and drug distribution coefficients (apparent partition coefficients) have been investigated for a number of narcotics and where possible for their congener narcotic antagonist. These studies were carried out by a novel microelectrometric titration technique as a function of temperature and pH. This method enables one to determine not only the dissociation constants to deconvolute overlapping pKa's, but also to determine the solubilities and oil-water distribution of these various drugs. The drug distribution coefficients displayed marked sensitivity to pH at values which span the range of attainable human physiological pH values. This has significant pharmacological implications for proper choice and scaling of drug dosages under various clinical situations among which are cited hyperventilation under a general anesthetic while concomitantly under a narcotic analgesic, obstetetrical analgesia, and medical and anti-abuse usage of narcotic antagonists. The partition coefficients and drug distribution coefficients were noticeably different at 20degreesC (where such measurements are customarily made) from those at 37degreesC (body temperature). Furthermore, various drugs exhibit very non-equivalent increases in drug distribution coefficients with increasing temperature, ranging from 21% for naltrexone. This non-regularity indicates that it will not be valid to extrapolate by any constant factor the measurements made at lower temperatures. Even the true partition coefficients increase with temperature from 20degrees to 37degreesC."}
{"id": "PMID:13979", "title": "Metabolism of sudoxicam by the rat, dog, and monkey.", "content": "Sudoxicam, N-(2-thiazolyl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1, 1-dioxide, was prepared in radiolabeled form and administered to rats, dogs, and monkeys. Urine contained approximately 60, 25, and 49% of the label given to rats, dogs, and monkeys, respectively; the remainder was cleared via feces. In addition to some unchanged drug, urine from all species examined contained two major metabolites. These were identified from their mass spectra as the thiohydantoic acid and thiourea resulting from scission of the thiazole ring of sudoxicam.", "contents": "Metabolism of sudoxicam by the rat, dog, and monkey. Sudoxicam, N-(2-thiazolyl)-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1, 1-dioxide, was prepared in radiolabeled form and administered to rats, dogs, and monkeys. Urine contained approximately 60, 25, and 49% of the label given to rats, dogs, and monkeys, respectively; the remainder was cleared via feces. In addition to some unchanged drug, urine from all species examined contained two major metabolites. These were identified from their mass spectra as the thiohydantoic acid and thiourea resulting from scission of the thiazole ring of sudoxicam."}
{"id": "PMID:13984", "title": "Clinical trial in post-addicts with oxilorphan (levo-BC-2605): a new narcotic antagonist.", "content": "Oxilorphan (levo-BC-2605) is a new, long-acting, narcotic antagonist that has agonist properties. Twenty-one (21) heroin addicts in Los Angeles were detoxified and given at least one oral dose of oxilorphan. Only three (14.3%) patients took daily doses for 14 days, which was the maximal time allowed for oxilorphan administration in this study. The remainder discontinued oxilorphan because of subjective side effects or for unknown reasons. Side effects most responsible for dropouts were dysphoria, insomnia, weakness, hallucinations, nausea, drowsiness and anorexia. Oxilorphan provided 24-hour protection with a single, oral dose, but subjective side effects encountered during inductiolinical trials with oxilorphan should be attempted with other addict populations to fully determine its potential therapeutic value.", "contents": "Clinical trial in post-addicts with oxilorphan (levo-BC-2605): a new narcotic antagonist. Oxilorphan (levo-BC-2605) is a new, long-acting, narcotic antagonist that has agonist properties. Twenty-one (21) heroin addicts in Los Angeles were detoxified and given at least one oral dose of oxilorphan. Only three (14.3%) patients took daily doses for 14 days, which was the maximal time allowed for oxilorphan administration in this study. The remainder discontinued oxilorphan because of subjective side effects or for unknown reasons. Side effects most responsible for dropouts were dysphoria, insomnia, weakness, hallucinations, nausea, drowsiness and anorexia. Oxilorphan provided 24-hour protection with a single, oral dose, but subjective side effects encountered during inductiolinical trials with oxilorphan should be attempted with other addict populations to fully determine its potential therapeutic value."}
{"id": "PMID:13980", "title": "Renal N-oxidation of trimethylamine in the chicken during tubular excretion.", "content": "The Sperber technique of infusion into the renal portal circulation in chickens was used to investigate in vivo the renal tubular transport and renal metabolism of trimethylamine (TMA). When 14C-TMA was infused at a rate of 1 x 10(-9) mol/min the transport efficiency (TE), that is, the tubular excretion of the 14C-label relative to excretion of simultaneously infused paminohippuric acid, was 0.70. Progressive addition of unlabeled TMA up to infusion rates of 1 x 10(-5) mol/min produced a progressive fall in the TE of the 14C-label. Identification of the 14C-label excreted in the urine revealed that approximately 85% of the infused 14C-TMA was excreted by the infused kidney as a single metabolite over the entire range of infusions. By use of the techniques of low-voltage electrophoresis, high-voltage electrophoretic mobility-pH profile, and gas chromatography/mass spectrometry, the renal metabolite was found to be identical with standard 14C-trimethylamine oxide (TMAO). At a TMA infusion rate of 1.5 x 10(-6) mol/kg/min reaching the infused kidney, the rate at which TMAO was formed and excreted by the kidney was 0.12 x 10(-6) mol per g of kidney per min. When 14C-TMAO was infused into chickens its TE was 0.11, which was not evidence for active excretory transport. Infused TMA was almost entirely metabolized in vivo to its N-oxide, TMAO, which then entered the urine. The renal tubular excretion of 14C during infusion of 14C-TMA was inhibited by the cationic blocker of transport, quinine, and by the anionic blocker of transport, probenecid.", "contents": "Renal N-oxidation of trimethylamine in the chicken during tubular excretion. The Sperber technique of infusion into the renal portal circulation in chickens was used to investigate in vivo the renal tubular transport and renal metabolism of trimethylamine (TMA). When 14C-TMA was infused at a rate of 1 x 10(-9) mol/min the transport efficiency (TE), that is, the tubular excretion of the 14C-label relative to excretion of simultaneously infused paminohippuric acid, was 0.70. Progressive addition of unlabeled TMA up to infusion rates of 1 x 10(-5) mol/min produced a progressive fall in the TE of the 14C-label. Identification of the 14C-label excreted in the urine revealed that approximately 85% of the infused 14C-TMA was excreted by the infused kidney as a single metabolite over the entire range of infusions. By use of the techniques of low-voltage electrophoresis, high-voltage electrophoretic mobility-pH profile, and gas chromatography/mass spectrometry, the renal metabolite was found to be identical with standard 14C-trimethylamine oxide (TMAO). At a TMA infusion rate of 1.5 x 10(-6) mol/kg/min reaching the infused kidney, the rate at which TMAO was formed and excreted by the kidney was 0.12 x 10(-6) mol per g of kidney per min. When 14C-TMAO was infused into chickens its TE was 0.11, which was not evidence for active excretory transport. Infused TMA was almost entirely metabolized in vivo to its N-oxide, TMAO, which then entered the urine. The renal tubular excretion of 14C during infusion of 14C-TMA was inhibited by the cationic blocker of transport, quinine, and by the anionic blocker of transport, probenecid."}
{"id": "PMID:13986", "title": "[An unusual case of panarteritis nodosa associated with chronic mercury poisoning (author's transl)].", "content": "In a 50-year-old woman, working as a dental assistant for more than ten years, chronic mercury poisoning developed insidiously, apparently from careless handling of mercury-amalgam. The main signs consisted of mental and neurological changes such as erethism, tremor and mercurial psellism. Peripheral arterial circulatory disorders occurred in the course of the disease, as well as abdominal colic and a polyneuropathy, which provided the first clues to panarteritis nodosa subsequently confirmed histologically.", "contents": "[An unusual case of panarteritis nodosa associated with chronic mercury poisoning (author's transl)]. In a 50-year-old woman, working as a dental assistant for more than ten years, chronic mercury poisoning developed insidiously, apparently from careless handling of mercury-amalgam. The main signs consisted of mental and neurological changes such as erethism, tremor and mercurial psellism. Peripheral arterial circulatory disorders occurred in the course of the disease, as well as abdominal colic and a polyneuropathy, which provided the first clues to panarteritis nodosa subsequently confirmed histologically."}
{"id": "PMID:13981", "title": "Studies on the N-demethylation and O-de-ethylation of ethylmorphine by hepatic microsomes from male rats.", "content": "On the basis of inhibition studies of the dealkylation of morphine and norcodeine, George and Tephly concluded that O-dealkylation and N-dealkylation are catalyzed by different enzymes. We have examined the microsomal dealkylation of 3-O-[1'-14Clethylmorphine by measuring HCHO colorimetrically and [1-14C]acetaldehyde radiometrically. We find that the KM for the O-de-ethylation is 57 muM, which is quite close to the KS(71 muM) for the type I binding of ethylmorphine in similar preparations. On the other hand, the KM for N-demethylation was 250 muM. Further, the N-demethylation was stoichiometric with the stimulation of both NADPH-cytochrome P-450 reductase and NADPH oxidase, whereas the sum of the N-demethylation and O-de-ethylation was significantly greater, suggesting that the O-de-ethylase activity does not involve stimulation of either of these two activities. Induction with phenobarbital increaesed N-demethylation 118% but did not affect O-de-ethylation. Finally, D2O inhibited the N-demethylase more than the O-de-ethylase.", "contents": "Studies on the N-demethylation and O-de-ethylation of ethylmorphine by hepatic microsomes from male rats. On the basis of inhibition studies of the dealkylation of morphine and norcodeine, George and Tephly concluded that O-dealkylation and N-dealkylation are catalyzed by different enzymes. We have examined the microsomal dealkylation of 3-O-[1'-14Clethylmorphine by measuring HCHO colorimetrically and [1-14C]acetaldehyde radiometrically. We find that the KM for the O-de-ethylation is 57 muM, which is quite close to the KS(71 muM) for the type I binding of ethylmorphine in similar preparations. On the other hand, the KM for N-demethylation was 250 muM. Further, the N-demethylation was stoichiometric with the stimulation of both NADPH-cytochrome P-450 reductase and NADPH oxidase, whereas the sum of the N-demethylation and O-de-ethylation was significantly greater, suggesting that the O-de-ethylase activity does not involve stimulation of either of these two activities. Induction with phenobarbital increaesed N-demethylation 118% but did not affect O-de-ethylation. Finally, D2O inhibited the N-demethylase more than the O-de-ethylase."}
{"id": "PMID:13988", "title": "Perfused lung preparation for studying altered gaseous environments.", "content": "An isolated perfused lung (IPL) preparation was used to investigate the influence of acute environmental stress on lung substrate metabolism. The IPL apparatus consists of four perfusion flasks housed in a temperature-controlled Lucite box with a circulation fan. Lungs are ventilated by a positive pressure ventilation pump. The ventilation is arranged so that the lung can be ventilated with any desired gas composition with concomitant collection of expired gases. The perfusion medium is circulated at 10 ml/min with a peristaltic blood pump, and passes through a specially designed chamber to dampen pulmonary pressure and remove emboli. The perfusion medium presently used in our experiments consisted of washed bovine red blood cells resuspended to a 15% hematocrit with Krebs-Henseleit bicarbonate buffer containing 6% dialyzed Pentex bovine serum albumin. Circulating substrates include 6muM glucose and 0.4muM palmitate. The pH is adjusted to 7.4 with 0.8M Na carbonate. Lungs perfused for 1.5 hr with this apparatus maintain viability, show little edema, maintain blood gases, and show linear incorporation of labeled glucose into lung lipids. Perfused lungs made hypocapnic show a significant (p less than 0.05) rise in lactate and pyruvate, while perfused lungs made hypercapnia show a significant decrease in pyruvate with no change in lactate.", "contents": "Perfused lung preparation for studying altered gaseous environments. An isolated perfused lung (IPL) preparation was used to investigate the influence of acute environmental stress on lung substrate metabolism. The IPL apparatus consists of four perfusion flasks housed in a temperature-controlled Lucite box with a circulation fan. Lungs are ventilated by a positive pressure ventilation pump. The ventilation is arranged so that the lung can be ventilated with any desired gas composition with concomitant collection of expired gases. The perfusion medium is circulated at 10 ml/min with a peristaltic blood pump, and passes through a specially designed chamber to dampen pulmonary pressure and remove emboli. The perfusion medium presently used in our experiments consisted of washed bovine red blood cells resuspended to a 15% hematocrit with Krebs-Henseleit bicarbonate buffer containing 6% dialyzed Pentex bovine serum albumin. Circulating substrates include 6muM glucose and 0.4muM palmitate. The pH is adjusted to 7.4 with 0.8M Na carbonate. Lungs perfused for 1.5 hr with this apparatus maintain viability, show little edema, maintain blood gases, and show linear incorporation of labeled glucose into lung lipids. Perfused lungs made hypocapnic show a significant (p less than 0.05) rise in lactate and pyruvate, while perfused lungs made hypercapnia show a significant decrease in pyruvate with no change in lactate."}
{"id": "PMID:13989", "title": "Increase in activity of partially purified alkaline phosphatase after treatment with Mg2+, Zn2+ and lysolecithin.", "content": "When lysolecithin predispersed in 0.15 mol/l KCl was sonicated with partially purified alkaline phosphatase, the enzyme activity was increased. Lysolecithin moderately modified the kinetic parameters by increasing the apparent Vmax and decreasing the apparent Km. The pH profile of the enzyme was shifted slightly from a peak at pH 9.5 for the soluble enzyme to a plateau between pH 9.5 and 10.2 for the lysolecithin enzyme mixture. In addition, lysolecithin enhanced the thermostability and resistance of the soluble enzyme preparation to chemical denaturants.", "contents": "Increase in activity of partially purified alkaline phosphatase after treatment with Mg2+, Zn2+ and lysolecithin. When lysolecithin predispersed in 0.15 mol/l KCl was sonicated with partially purified alkaline phosphatase, the enzyme activity was increased. Lysolecithin moderately modified the kinetic parameters by increasing the apparent Vmax and decreasing the apparent Km. The pH profile of the enzyme was shifted slightly from a peak at pH 9.5 for the soluble enzyme to a plateau between pH 9.5 and 10.2 for the lysolecithin enzyme mixture. In addition, lysolecithin enhanced the thermostability and resistance of the soluble enzyme preparation to chemical denaturants."}
{"id": "PMID:13990", "title": "Changes in the activities of the enzymes of hepatic ketogenesis in the rat between late fetal life and weaning.", "content": "The activities of hydroxymethylglutaryl-CoA synthase and hydroxymethylglutaryl-CoA lyase have been determined in the mitochondria and cytosol of the liver during development of the rat. Both mitochondrial enzymes exhibit similar developmental patterns with rapid rises in activity after birth, peaks of activity during early and late suckling and a trough during the mid-suckling period and a slight fall in activity (to the adult values) after weaning. Both cytosolic enzymes have low activities at all ages studied and exhibit no major developmental changes.", "contents": "Changes in the activities of the enzymes of hepatic ketogenesis in the rat between late fetal life and weaning. The activities of hydroxymethylglutaryl-CoA synthase and hydroxymethylglutaryl-CoA lyase have been determined in the mitochondria and cytosol of the liver during development of the rat. Both mitochondrial enzymes exhibit similar developmental patterns with rapid rises in activity after birth, peaks of activity during early and late suckling and a trough during the mid-suckling period and a slight fall in activity (to the adult values) after weaning. Both cytosolic enzymes have low activities at all ages studied and exhibit no major developmental changes."}
{"id": "PMID:13991", "title": "Regulation of nitrogen catabolic enzymes in chick liver: effects of insulin.", "content": "Previous studies have shown that a group of nitrogen catabolic enzymes including xanthine dehydrogenase, purine nucleoside phosphorylase, and tyrosine aminotransferase are all increased in chick liver by dietary protein as well as single amino acids (e.g. methionine) and certain antimetabolites (e.g. hydrazine). A similar enzyme response pattern can be obtained with insulin. This hormone causes an enhanced rate of XDH synthesis and gives nonadditive results with protein, hydrazine and methionine. Furthermore, a vitamin B6 dependency was observed in responses to both high protein diets and insulin, all suggesting a common regulatory mechanism. In this system dietary protein and insulin may act similarly by increasing the availability of amino acids to the liver -- in one case by supplying amino acids through the diet and in the other by increasing amino acid uptake.", "contents": "Regulation of nitrogen catabolic enzymes in chick liver: effects of insulin. Previous studies have shown that a group of nitrogen catabolic enzymes including xanthine dehydrogenase, purine nucleoside phosphorylase, and tyrosine aminotransferase are all increased in chick liver by dietary protein as well as single amino acids (e.g. methionine) and certain antimetabolites (e.g. hydrazine). A similar enzyme response pattern can be obtained with insulin. This hormone causes an enhanced rate of XDH synthesis and gives nonadditive results with protein, hydrazine and methionine. Furthermore, a vitamin B6 dependency was observed in responses to both high protein diets and insulin, all suggesting a common regulatory mechanism. In this system dietary protein and insulin may act similarly by increasing the availability of amino acids to the liver -- in one case by supplying amino acids through the diet and in the other by increasing amino acid uptake."}
{"id": "PMID:13992", "title": "Recent advances in equine reproduction.", "content": "Mares rarely ovulate in winter; ovulation is induced by increase in daylight length. Ova accumulate in the oviducts of unserved mares. During pregnancy, corpora lutea accumulate; all regress together at mid pregnancy. Plasma progesterone levels rise and oestrogen levels fall towards the end of pregnancy. Methods are available for early termination of pregnancy and for induction of parturition. Pregnancy can be diagnosed efficiently by rectal examination, and by immunological assay of pregnant mare serum gonadotrophin. Service at the foal heat is associated with an increased prevalence of early embryonic death; twinning is the commonest single cause of abortion. Spontaneous prolonged dioestrus is common in summer but may be effectively treated. Bacterial endometritis may result mainly from secondary pathogenic activity by organisms of the normal uterine flora; diagnosis by endometrial smear examination is accurate and methods of treatment have improved. The virus of horse pox has been identified, and the occurrence of equine infection with Mycoplasma has been confirmed. In the male, recent work has emphasized that reproductive function is seasonal. The presence or absence of an undescended testis can now be accurately determined.", "contents": "Recent advances in equine reproduction. Mares rarely ovulate in winter; ovulation is induced by increase in daylight length. Ova accumulate in the oviducts of unserved mares. During pregnancy, corpora lutea accumulate; all regress together at mid pregnancy. Plasma progesterone levels rise and oestrogen levels fall towards the end of pregnancy. Methods are available for early termination of pregnancy and for induction of parturition. Pregnancy can be diagnosed efficiently by rectal examination, and by immunological assay of pregnant mare serum gonadotrophin. Service at the foal heat is associated with an increased prevalence of early embryonic death; twinning is the commonest single cause of abortion. Spontaneous prolonged dioestrus is common in summer but may be effectively treated. Bacterial endometritis may result mainly from secondary pathogenic activity by organisms of the normal uterine flora; diagnosis by endometrial smear examination is accurate and methods of treatment have improved. The virus of horse pox has been identified, and the occurrence of equine infection with Mycoplasma has been confirmed. In the male, recent work has emphasized that reproductive function is seasonal. The presence or absence of an undescended testis can now be accurately determined."}
{"id": "PMID:13993", "title": "Heart rate and ventilation in relation to venous [K+], osmolality, pH, PCO2, PO2, [orthophosphate], and [lactate] at transition from rest to exercise in athletes and non-athletes.", "content": "To evaluate to what metabolci event in contracting muscles heart rate (HR) and VE are related, time courses of femoral and cubital venous [K=], osomolality (OSM), pH, POC2, PO2, [lactate], and [orthophosphate] ([Pi]) at onset of exercise were studied in athletes (TR) and non-athletes (UT) and compared to time courses of HR and VE. During ischaemic work with the calf muscles it could be shown that most of these blood constituents were only released from contracting muscles. Thus their time courses reflected the metabolic events in working muscles being not essentially disturbed by non-working parts of the body. Ischaemic work induced, however, substantial increases of HR and VE. In the course of non-ischaemic bicycle work HR and VE rose more rapidly in TR than in UT but were lower in TR during the steady state. During non-ischaemic work only the increased of femoral venous [K=1 closely mimicked the cardiorespiratory transients in TR as well as in UT. None of the other femoral venous substances showed such a rapid change or such typical variations between TR and UT. Cubital venous [K=1 and [Pi] approached femoral  venous concentrations only in second minute after start whereas pH, PCO2, and OSM increased mainly in venous outflow from contracting muscles. PO2 decreased in femoral venous blood of TR and UT, but in cubital venous blood it remained depressed only in UT. It was discussed that the cardiorespiratory adjustment during the initial stages of work was related to K+ release in working muscles and not to O2 consuming or H+ producing processes, nor to release of Pi or increase of OSM.", "contents": "Heart rate and ventilation in relation to venous [K+], osmolality, pH, PCO2, PO2, [orthophosphate], and [lactate] at transition from rest to exercise in athletes and non-athletes. To evaluate to what metabolci event in contracting muscles heart rate (HR) and VE are related, time courses of femoral and cubital venous [K=], osomolality (OSM), pH, POC2, PO2, [lactate], and [orthophosphate] ([Pi]) at onset of exercise were studied in athletes (TR) and non-athletes (UT) and compared to time courses of HR and VE. During ischaemic work with the calf muscles it could be shown that most of these blood constituents were only released from contracting muscles. Thus their time courses reflected the metabolic events in working muscles being not essentially disturbed by non-working parts of the body. Ischaemic work induced, however, substantial increases of HR and VE. In the course of non-ischaemic bicycle work HR and VE rose more rapidly in TR than in UT but were lower in TR during the steady state. During non-ischaemic work only the increased of femoral venous [K=1 closely mimicked the cardiorespiratory transients in TR as well as in UT. None of the other femoral venous substances showed such a rapid change or such typical variations between TR and UT. Cubital venous [K=1 and [Pi] approached femoral  venous concentrations only in second minute after start whereas pH, PCO2, and OSM increased mainly in venous outflow from contracting muscles. PO2 decreased in femoral venous blood of TR and UT, but in cubital venous blood it remained depressed only in UT. It was discussed that the cardiorespiratory adjustment during the initial stages of work was related to K+ release in working muscles and not to O2 consuming or H+ producing processes, nor to release of Pi or increase of OSM."}
{"id": "PMID:13994", "title": "Photooxidation of human serum albumin and its complex with bilirubin.", "content": "Irradiation with visible light of human serum albumin in aqueous solution at pH 8, in the presence of catalytic amounts of rose bengal or methylene blue, resulted in random oxidation of the histidine residues in the protein under consumption of one mole O2, and release of somewhat less than one proton, per histidine residue degraded. An increase of light absorption at 250 nm was proportional to the amount of oxygen consumed. Bilirubin bound to the oxidized protein showed an increased light absorption at its maximum, 460 nm, and a decreased binding affinity, indicating a conformational change of the protein on oxidation of histidine residues. This change also resulted in a slight perturbation of tyrosine light absorption, corresponding to a shift of the chromophore to more polar surroundings. Further, a sensitized oligomerization of albumin was observed, independent of oxidation of the histidine residues, and not consuming oxygen. Irradiation of a complex of human serum albumin with one molecule of bound bilirubin, in the absence of a sensitizing dye, resulted in a fast, non-oxygen consuming process whereby the light absorption maximum of the pigment was shifted 4 nm towards longer wavelength and part of the bilirubin was converted to a more polar pigment, bound less firmly to the protein. This was followed by a relatively slow oxidation of the pigment under uptake of one mole O2. Parallel photooxidation of the protein carrier could not be detected. It is considered possible that the fast, anaerobic process is operative in phototherapy of hyperbilirubinemia in the newborn. Serum albumin is probably not oxidized during this treatment.", "contents": "Photooxidation of human serum albumin and its complex with bilirubin. Irradiation with visible light of human serum albumin in aqueous solution at pH 8, in the presence of catalytic amounts of rose bengal or methylene blue, resulted in random oxidation of the histidine residues in the protein under consumption of one mole O2, and release of somewhat less than one proton, per histidine residue degraded. An increase of light absorption at 250 nm was proportional to the amount of oxygen consumed. Bilirubin bound to the oxidized protein showed an increased light absorption at its maximum, 460 nm, and a decreased binding affinity, indicating a conformational change of the protein on oxidation of histidine residues. This change also resulted in a slight perturbation of tyrosine light absorption, corresponding to a shift of the chromophore to more polar surroundings. Further, a sensitized oligomerization of albumin was observed, independent of oxidation of the histidine residues, and not consuming oxygen. Irradiation of a complex of human serum albumin with one molecule of bound bilirubin, in the absence of a sensitizing dye, resulted in a fast, non-oxygen consuming process whereby the light absorption maximum of the pigment was shifted 4 nm towards longer wavelength and part of the bilirubin was converted to a more polar pigment, bound less firmly to the protein. This was followed by a relatively slow oxidation of the pigment under uptake of one mole O2. Parallel photooxidation of the protein carrier could not be detected. It is considered possible that the fast, anaerobic process is operative in phototherapy of hyperbilirubinemia in the newborn. Serum albumin is probably not oxidized during this treatment."}
{"id": "PMID:13995", "title": "CO2-mediated control of fatty acid metabolism in isolated hamster brown-fat cells during norepinephrine stimulation.", "content": "1. Addition of norepinephrine to isolated hamster brown-fat cells suspended in Krebs-Ringer phosphate buffer induces a pronounced, but temporary increase in respiratory rate. 2. If Krebs-Ringer phosphate buffer is bubbled with CO2 prior to the addition of cells and norepinephrine, the respiratory capacity of the cells is further potentiated and most important, the respiration is maintained at a high rate until the medium becomes depleted of oxygen. 3. This respiratory pattern cannot be obtained in CO2-bubbled Krebs-Ringer bicarbonate buffer. 4. The results indicate that CO2 has a regulatory effect on fatty acid metabolism in isolated hamster brown-fat cells.", "contents": "CO2-mediated control of fatty acid metabolism in isolated hamster brown-fat cells during norepinephrine stimulation. 1. Addition of norepinephrine to isolated hamster brown-fat cells suspended in Krebs-Ringer phosphate buffer induces a pronounced, but temporary increase in respiratory rate. 2. If Krebs-Ringer phosphate buffer is bubbled with CO2 prior to the addition of cells and norepinephrine, the respiratory capacity of the cells is further potentiated and most important, the respiration is maintained at a high rate until the medium becomes depleted of oxygen. 3. This respiratory pattern cannot be obtained in CO2-bubbled Krebs-Ringer bicarbonate buffer. 4. The results indicate that CO2 has a regulatory effect on fatty acid metabolism in isolated hamster brown-fat cells."}
{"id": "PMID:13996", "title": "Synthesis of stereospecifically deuterated phenylalamines and determination of their configuration.", "content": "1. Starting from trans-cinnamic acid a chiral (-)3-phenyl-[2,3-2H]propionic acid has been synthesized using Clostridium kiuyveri cells as catalyst. 2. The chiral dideuterated acid has been converted by chemical methods to a mixture of (2R) and (2S)-phenyl[2,3-2H]-alanine. 3. By means of 1H nuclear magnetic resonance spectroscopy and the action of D and L-amino acid oxidase the configuration of the phenylalamine has been shown to be (2R, 3S) and (2S, 3S), respectively. The labelled phenylalanine is thus sterically and isotopically homogenous at position 3 but heterogenous at position 2.", "contents": "Synthesis of stereospecifically deuterated phenylalamines and determination of their configuration. 1. Starting from trans-cinnamic acid a chiral (-)3-phenyl-[2,3-2H]propionic acid has been synthesized using Clostridium kiuyveri cells as catalyst. 2. The chiral dideuterated acid has been converted by chemical methods to a mixture of (2R) and (2S)-phenyl[2,3-2H]-alanine. 3. By means of 1H nuclear magnetic resonance spectroscopy and the action of D and L-amino acid oxidase the configuration of the phenylalamine has been shown to be (2R, 3S) and (2S, 3S), respectively. The labelled phenylalanine is thus sterically and isotopically homogenous at position 3 but heterogenous at position 2."}
{"id": "PMID:13997", "title": "Stereospecificity of phenylpyruvate tautomerase. A convenient method for the preparation of chirally labelled phenylpyruvates.", "content": "1. By 1H nuclear magnetic resonance spectroscopy it has been shown that phenylpyruvate tautomerase from beef kidney catalyses the stereospecific exchange of one of the enantiotopic 3H-atoms in the side-chain of the substrate with solvent protons, the rate of spontaneous exchange being slow under physiological conditions. 2. Using monodeuterated phenylpyruvate of known absolute configuration it has been shown that the tautomerase removes specifically the 3-pro-R hydrogen atom of the substrate. 3. The circular dichroism spectra of the two enantiomeric 3-phenyl-[3-2H]pyruvates have been determined. 4. Some implications of these findings for the investigation of the metabolism of aromatic amino acids are discussed.", "contents": "Stereospecificity of phenylpyruvate tautomerase. A convenient method for the preparation of chirally labelled phenylpyruvates. 1. By 1H nuclear magnetic resonance spectroscopy it has been shown that phenylpyruvate tautomerase from beef kidney catalyses the stereospecific exchange of one of the enantiotopic 3H-atoms in the side-chain of the substrate with solvent protons, the rate of spontaneous exchange being slow under physiological conditions. 2. Using monodeuterated phenylpyruvate of known absolute configuration it has been shown that the tautomerase removes specifically the 3-pro-R hydrogen atom of the substrate. 3. The circular dichroism spectra of the two enantiomeric 3-phenyl-[3-2H]pyruvates have been determined. 4. Some implications of these findings for the investigation of the metabolism of aromatic amino acids are discussed."}
{"id": "PMID:13998", "title": "Mitochondrial and cytosolic NADPH systems and isocitrate dehydrogenase indicator metabolites during ureogensis from ammonia in isolated rat hepatocytes.", "content": "1. Citrate isocitrate and 2-oxoglutarate levels were determined in isolated rat hepatocytes and in particulate and soluble fractions, thereof, obtained by the digitonin and silicone oil fractionation technique. 2. Caculated from isocitrate/2-oxoglutarate ratios (\"indicator metabolite method\"), the redox potential of mitochondrial free NADPH is -402 mV, whereas that of the extramitochondrial (cytosolic) space is about 10 mV more positive, -392 mV. 3; Addition of ammonia (either as ammonium chloride or from urea plus urease) to isolated hepatocytes causes preferential oxidation of mitochondrial NADPH, is demonstrated by spectrophotometry of the dihydro band and by the changes in the isocitrate/2-oxoglutarate ratios. The redox potential difference of free NADPH between mitochondria and cytosol is abolished or even reserved. 4. It is concluded that during urogenesis from ammonia mitochondrial isocitrate oxidation is shifted largely in favor of the NADP-linked as opposed to the NAD-linked enzyme; isocitrate concentration under these conditions is less than 10 muM, below the Km (isocitrate) of the NAD-linked enzyme but in the range of that for the NADP-linked enzyme. 5. Both in the absence and in the presence of ammonia there is a concentration gradient across the mitochondrial inner membrane (from mitochondria to cytosol) for citrate, isocitrate, and also, to a smaller extent, for 2-oxoglutarate. 6. These results and data in the literature on enzyme activity are in agreement with the assumption of near-equilibrium of NADP-dependent isocitrate dehydrogenases in the mitochondrial matrix and cytosolic spaces in the absence of ammonia; accordingly, during urea formation from added ammonia the redox potential of mitochondrial free NADPH is increased to -391 mV or possibly even higher if there exists an indicator error under this condition.", "contents": "Mitochondrial and cytosolic NADPH systems and isocitrate dehydrogenase indicator metabolites during ureogensis from ammonia in isolated rat hepatocytes. 1. Citrate isocitrate and 2-oxoglutarate levels were determined in isolated rat hepatocytes and in particulate and soluble fractions, thereof, obtained by the digitonin and silicone oil fractionation technique. 2. Caculated from isocitrate/2-oxoglutarate ratios (\"indicator metabolite method\"), the redox potential of mitochondrial free NADPH is -402 mV, whereas that of the extramitochondrial (cytosolic) space is about 10 mV more positive, -392 mV. 3; Addition of ammonia (either as ammonium chloride or from urea plus urease) to isolated hepatocytes causes preferential oxidation of mitochondrial NADPH, is demonstrated by spectrophotometry of the dihydro band and by the changes in the isocitrate/2-oxoglutarate ratios. The redox potential difference of free NADPH between mitochondria and cytosol is abolished or even reserved. 4. It is concluded that during urogenesis from ammonia mitochondrial isocitrate oxidation is shifted largely in favor of the NADP-linked as opposed to the NAD-linked enzyme; isocitrate concentration under these conditions is less than 10 muM, below the Km (isocitrate) of the NAD-linked enzyme but in the range of that for the NADP-linked enzyme. 5. Both in the absence and in the presence of ammonia there is a concentration gradient across the mitochondrial inner membrane (from mitochondria to cytosol) for citrate, isocitrate, and also, to a smaller extent, for 2-oxoglutarate. 6. These results and data in the literature on enzyme activity are in agreement with the assumption of near-equilibrium of NADP-dependent isocitrate dehydrogenases in the mitochondrial matrix and cytosolic spaces in the absence of ammonia; accordingly, during urea formation from added ammonia the redox potential of mitochondrial free NADPH is increased to -391 mV or possibly even higher if there exists an indicator error under this condition."}
{"id": "PMID:13999", "title": "Preparation of coenzymic activity of soluble polyethyleneimine-bound NADP+ derivatives.", "content": "Alkylation at N-1 of the NADP+ adenine ring with 3,4-epoxybutanoic acid gave 1-(2-hydroxy-3-carboxypropyl)-NADP+. Enzymic reduction of the latter, followed by alkaline Dimroth rearrangement and enzymic reoxidation, gave N6-(2-hydroxy-3-carboxypropyl)-NADP+. On the other hand, bromination at C-8 of the NADP+ adenine ring, followed by reaction with the disodium salt of 3-mercaptroproionic acid, gave 8-(2-carboxyethylthio)-NADP+. Carbodimide coupling of the three carboxylic NADP+ derivatives to polyethyleneimine afforded the corresponding macromolecular NADP+ analogues. The carboxylic and the polyethyleneimine derivatives synthesized have been shown to be co-enzymically active with yeast glucose-6-phosphate dehydrogenase, liver glutamate dehydrogenase and yeast aldehyde dehydrogenase. The degree of efficiency relative to NADP+ with the three enzymes ranged from 17% to 100% for the carboxylic derivatives and from 1% to 36% for the polyethyleneimine analogues. On comparing the efficiences with the three enzymes of the N-1 derivatives to the one of the corresponding N6 anc C-8 analogues, the order of activity was N-1 greater than N6 greater C-8, except in the case of the carboxylic compounds with glutamate dehydrogenase, where this order was inverted. None of these modified cofactors were active with pig heart isocitrate dehydrogenase.", "contents": "Preparation of coenzymic activity of soluble polyethyleneimine-bound NADP+ derivatives. Alkylation at N-1 of the NADP+ adenine ring with 3,4-epoxybutanoic acid gave 1-(2-hydroxy-3-carboxypropyl)-NADP+. Enzymic reduction of the latter, followed by alkaline Dimroth rearrangement and enzymic reoxidation, gave N6-(2-hydroxy-3-carboxypropyl)-NADP+. On the other hand, bromination at C-8 of the NADP+ adenine ring, followed by reaction with the disodium salt of 3-mercaptroproionic acid, gave 8-(2-carboxyethylthio)-NADP+. Carbodimide coupling of the three carboxylic NADP+ derivatives to polyethyleneimine afforded the corresponding macromolecular NADP+ analogues. The carboxylic and the polyethyleneimine derivatives synthesized have been shown to be co-enzymically active with yeast glucose-6-phosphate dehydrogenase, liver glutamate dehydrogenase and yeast aldehyde dehydrogenase. The degree of efficiency relative to NADP+ with the three enzymes ranged from 17% to 100% for the carboxylic derivatives and from 1% to 36% for the polyethyleneimine analogues. On comparing the efficiences with the three enzymes of the N-1 derivatives to the one of the corresponding N6 anc C-8 analogues, the order of activity was N-1 greater than N6 greater C-8, except in the case of the carboxylic compounds with glutamate dehydrogenase, where this order was inverted. None of these modified cofactors were active with pig heart isocitrate dehydrogenase."}
{"id": "PMID:14000", "title": "Purification and properties of blood-group-specific lectins from Vicia cracca.", "content": "The lectins from the seeds of Vicia cracca react specifically with human blood group A erythrocytes. They were purified by affinity chromatography on an adsorbent containing matrix-bound N-acyl-D-galactosamine. By a continuous pH gradient the lectins could be separated into two fractions each of which was shown to consist of several agglutinating species. The behaviour of both fractions in affinity chromatography was paralleled by the pH dependence of the interaction with the hapten sugar N-acetyl-D-galactosamine. Both lectin fractions have the same molecular (125000) and subunit (33000) weights, display the same pH dependence of their titre against A1 erythrocytes, and bind to N-acetyl-D-galactosamine at pH 8 with the same constant of about 6 X 10(3)M-1.", "contents": "Purification and properties of blood-group-specific lectins from Vicia cracca. The lectins from the seeds of Vicia cracca react specifically with human blood group A erythrocytes. They were purified by affinity chromatography on an adsorbent containing matrix-bound N-acyl-D-galactosamine. By a continuous pH gradient the lectins could be separated into two fractions each of which was shown to consist of several agglutinating species. The behaviour of both fractions in affinity chromatography was paralleled by the pH dependence of the interaction with the hapten sugar N-acetyl-D-galactosamine. Both lectin fractions have the same molecular (125000) and subunit (33000) weights, display the same pH dependence of their titre against A1 erythrocytes, and bind to N-acetyl-D-galactosamine at pH 8 with the same constant of about 6 X 10(3)M-1."}
{"id": "PMID:14001", "title": "Biophysical and enzymological studies upon the interaction of trans-cinnamic acid with higher plant microsomal cytochromes P-450.", "content": "The interaction of trans-cinnamic acid with the cytochrome P-450 of microsomes derived from washed potato slices has been studied. The washing process increased the specific content of microsomal electron transport components and hence provided a useful material in which to study the interaction. Evidence is presented that the trans-cinnamic acid interacts with the cytochrome P-450, and that this interaction is analogous to \"type 1\" interactions of other cytochrome P-450 systems. This evidence includes the formation of a \"type 1\" substrate binding spectrum, an increased rate of reduction of cytochrome P-450 by NADPH in the presence of trans-cinnamic acid, an increased oxygen uptake and NADPH oxidation when trans-cinnamic acid is added to the microsomes in the presence of NADPH, and a close correlation between biophysical parameters of electron transport in the cytochrome P-450 system and enzymological parameters of the trans-cinnamic acid 4-hydroxulation reaction. The investigation has been extended to cytochrome P-450 systems of other tissues and it has been found that the trans-cinnamic acid 4-hydroxylation reaction cannot account for the presence of most of th cytochrome P-450 in several tissues. This suggests that other functions of higher plant cytochrome P-450 chains exist, and that the substrate specificityof the hemoprotein may vary in different plant tissues.", "contents": "Biophysical and enzymological studies upon the interaction of trans-cinnamic acid with higher plant microsomal cytochromes P-450. The interaction of trans-cinnamic acid with the cytochrome P-450 of microsomes derived from washed potato slices has been studied. The washing process increased the specific content of microsomal electron transport components and hence provided a useful material in which to study the interaction. Evidence is presented that the trans-cinnamic acid interacts with the cytochrome P-450, and that this interaction is analogous to \"type 1\" interactions of other cytochrome P-450 systems. This evidence includes the formation of a \"type 1\" substrate binding spectrum, an increased rate of reduction of cytochrome P-450 by NADPH in the presence of trans-cinnamic acid, an increased oxygen uptake and NADPH oxidation when trans-cinnamic acid is added to the microsomes in the presence of NADPH, and a close correlation between biophysical parameters of electron transport in the cytochrome P-450 system and enzymological parameters of the trans-cinnamic acid 4-hydroxulation reaction. The investigation has been extended to cytochrome P-450 systems of other tissues and it has been found that the trans-cinnamic acid 4-hydroxylation reaction cannot account for the presence of most of th cytochrome P-450 in several tissues. This suggests that other functions of higher plant cytochrome P-450 chains exist, and that the substrate specificityof the hemoprotein may vary in different plant tissues."}
{"id": "PMID:14002", "title": "Detergent-resistant phospholipase A of Escherichia coli K-12. Purification and properties.", "content": "Detergent-resistant phospholipase A, which is tightly bound to the outer membranes of Escherichia coli K-12 cells, was purified approximately 2000-fold to near homogeneity by solubilization with sodium dodecylsulfate and butan-1-ol, acid precipitation, acetone fractionation and column chromatographies on Sephadex G-100 in the presence of sodium dodecylsulfate and on DEAE-cellulose in the presence of Triton X-100. The final preparation showed a single band in the sodium dodecylsulfate gel system. The enzyme hydrolyzes both the 1-acyl and 2-acyl chains of phosphatidylethanolamine or phosphatidylcholine. It also attacks 1-acyl and 2-acylglycerylphosphorylethanolamine. Thus, this enzyme shows not only phospholipase A1 and lysophospholipase L1 activities but also phospholipase A2 and lysophospholipase L2 activities. The enzyme lost its activity completely on incubation at 80 degrees C for 5 min at either pH 6.4 or pH 8.0. It was stable in 0.5% sodium dodecylsulfate at below 40 degrees C. The enzyme was inactivated on incubation for 5 min at 90 degrees C in 1% sodium dodecylsulfate/1% 2-mercaptoethanol/4 M urea. The native and inactivated enzymes showed different protein bands with RF values corresponding to Mr 21 000 and Mr 28 000 respectively, in a sodium dodecylsulfate gel system. Triton X-100 seemed to protect the enzyme from inactivation. The purified enzyme was fully active on phosphatidylethanolamine in the presence of 0.0002% or 0.05% Triton X-100. The enzyme requires Ca2+. From its properties this enzyme seems to be identical with the enzyme purified from crude extracts of Escherichia coli B by Scandella and Kornberg. However, it differs from the latter in its positional specificity and susceptibility to sodium dodecylsulfate. Possible explanation of the difference of positional specificity of the two preparations is also described.", "contents": "Detergent-resistant phospholipase A of Escherichia coli K-12. Purification and properties. Detergent-resistant phospholipase A, which is tightly bound to the outer membranes of Escherichia coli K-12 cells, was purified approximately 2000-fold to near homogeneity by solubilization with sodium dodecylsulfate and butan-1-ol, acid precipitation, acetone fractionation and column chromatographies on Sephadex G-100 in the presence of sodium dodecylsulfate and on DEAE-cellulose in the presence of Triton X-100. The final preparation showed a single band in the sodium dodecylsulfate gel system. The enzyme hydrolyzes both the 1-acyl and 2-acyl chains of phosphatidylethanolamine or phosphatidylcholine. It also attacks 1-acyl and 2-acylglycerylphosphorylethanolamine. Thus, this enzyme shows not only phospholipase A1 and lysophospholipase L1 activities but also phospholipase A2 and lysophospholipase L2 activities. The enzyme lost its activity completely on incubation at 80 degrees C for 5 min at either pH 6.4 or pH 8.0. It was stable in 0.5% sodium dodecylsulfate at below 40 degrees C. The enzyme was inactivated on incubation for 5 min at 90 degrees C in 1% sodium dodecylsulfate/1% 2-mercaptoethanol/4 M urea. The native and inactivated enzymes showed different protein bands with RF values corresponding to Mr 21 000 and Mr 28 000 respectively, in a sodium dodecylsulfate gel system. Triton X-100 seemed to protect the enzyme from inactivation. The purified enzyme was fully active on phosphatidylethanolamine in the presence of 0.0002% or 0.05% Triton X-100. The enzyme requires Ca2+. From its properties this enzyme seems to be identical with the enzyme purified from crude extracts of Escherichia coli B by Scandella and Kornberg. However, it differs from the latter in its positional specificity and susceptibility to sodium dodecylsulfate. Possible explanation of the difference of positional specificity of the two preparations is also described."}
{"id": "PMID:14003", "title": "Relation between the gradient of the ATP/ADP ratio and the membrane potential across the mitochondrial membrane.", "content": "The relation between the intramitochondrial and extramitochondrial ratio ATP/ADP, the transmembrane potential and pH gradient is investigated in the present communication. For this purpose mitochondria are equilibrated with added [14C]ATP in the presence of substrate and oligomycin for eliminating phosphate transfer by ATPase. The membrane potential was measured by the distribution of 86Rb+ in the presence of valinomycin, the  deltapH by the distribution of [14C]acetate. In the energized state by varying deltapsi between 60 and 160 mV, the internal (ATP/ADP)i is decreased 30-fold, the external (ATP/ADP)e remains largely constant. As a result, the deltalog (ATP/ADP)e/(ATP/ADP)i = deltalogphi is increased linerly with deltapsi according to the following relation: deltalogphi = 0.85 deltapsi - 0.35. The deltapH was changed between 0.1 and 0.8 by increasing the Pi concentration causing only a minor decrease of deltalogphi would be expected if the ATP-ADP exchange has a significant electroneutral portion. Also in the uncoupled and respiration-inhibited state the same function between deltalogphi and deltapsi is found as in the energized states. It is concluded that under these conditions the ATP-ADP exchange is largely electrical.", "contents": "Relation between the gradient of the ATP/ADP ratio and the membrane potential across the mitochondrial membrane. The relation between the intramitochondrial and extramitochondrial ratio ATP/ADP, the transmembrane potential and pH gradient is investigated in the present communication. For this purpose mitochondria are equilibrated with added [14C]ATP in the presence of substrate and oligomycin for eliminating phosphate transfer by ATPase. The membrane potential was measured by the distribution of 86Rb+ in the presence of valinomycin, the  deltapH by the distribution of [14C]acetate. In the energized state by varying deltapsi between 60 and 160 mV, the internal (ATP/ADP)i is decreased 30-fold, the external (ATP/ADP)e remains largely constant. As a result, the deltalog (ATP/ADP)e/(ATP/ADP)i = deltalogphi is increased linerly with deltapsi according to the following relation: deltalogphi = 0.85 deltapsi - 0.35. The deltapH was changed between 0.1 and 0.8 by increasing the Pi concentration causing only a minor decrease of deltalogphi would be expected if the ATP-ADP exchange has a significant electroneutral portion. Also in the uncoupled and respiration-inhibited state the same function between deltalogphi and deltapsi is found as in the energized states. It is concluded that under these conditions the ATP-ADP exchange is largely electrical."}
{"id": "PMID:14004", "title": "Stabilization of human beta-D-N-acetylhexosaminidase A towards proteolytic inactivation by coupling it to poly(N-vinylpyrrolidone).", "content": "Human hexosaminidase A was covalently bound to soluble poly(N-vinylpyrrolidone), and the effect of this binding on the enzyme inactivation by various procedures was investigated. Whereas the polymer-bound hexosaminidase underwent inactivation to the same extent as the free enzyme, when exposed to heat or acidic pH, the conjugation to polymer appeared to protect the enzyme towards proteolysis. Thus, the polymer-bound enzyme exhibited considerably higher resistance to treatment of both pronase and macrophage cathepsins. The clearance rate from rabbit blood, of the polymer-bound enzyme (expressed as enzyme activity), was shown to be significantly slower than that of the free enzyme.", "contents": "Stabilization of human beta-D-N-acetylhexosaminidase A towards proteolytic inactivation by coupling it to poly(N-vinylpyrrolidone). Human hexosaminidase A was covalently bound to soluble poly(N-vinylpyrrolidone), and the effect of this binding on the enzyme inactivation by various procedures was investigated. Whereas the polymer-bound hexosaminidase underwent inactivation to the same extent as the free enzyme, when exposed to heat or acidic pH, the conjugation to polymer appeared to protect the enzyme towards proteolysis. Thus, the polymer-bound enzyme exhibited considerably higher resistance to treatment of both pronase and macrophage cathepsins. The clearance rate from rabbit blood, of the polymer-bound enzyme (expressed as enzyme activity), was shown to be significantly slower than that of the free enzyme."}
{"id": "PMID:14005", "title": "The effect of Mg2+ on the Ca2+-binding properties of non-activated phosphorylase kinase.", "content": "The calcium binding properties of non-activated phosphorylase kinase at pH 6.8 have been studied by the gel filtration technique at calcium concentrations from 50 nM to 50 muM. Taking into account the subunit structure alpha4beta4gamma4 the enzyme binds 12 mol Ca2+ per mol with an association constant of 6.0 X 10(7) M-1, 4 mol with an association constant of 1.7 X 10(6) M-1 and 36 mol with a binding constant of 3.9 X 10(4) M-1 at low ionic strength. In buffer of high ionic strength, i.e. 180 mM NH4Cl or 60 mM (NH4)2SO4, only a single set of eight binding sites with a binding constant of 5.5 X 10(7) M-1 is left. In a buffer containing 155 mM NH4Cl and 10 mM MgCl2, the calcium affinity of these sites is reduced to a KCa of 3.0 X 10(6) M-1, indicating competition between Ca2+ and Mg2+. From these measurements, the binding constant of Mg2+ for these sites is calculated to be 1.7 X 10(3) M-1 is left. In a buffer containing 155 mM NH4Cl and 10 mM MgCl2, the calcium affinity of these sites is reduced to a KCa of 3.0 X 10(6) M-1, indicating competition between Ca2+ and Mg2+. from these measurements, the binding constant of Mg2+ for these sites is calculated to be 1.7 X 10(3) M-1. Additionally, 10 mM Mg2+ induces a set of four new Ca2+ binding sites which show positive cooperativity. Their half-saturation constant under the conditions described is 3.5 X 10(5) M-1, and they, too, exhibit competition between Ca2+ and Mg2+. Since this set of sites is induced by Mg2+ a third group of binding sites for the latter metal must be postulated.", "contents": "The effect of Mg2+ on the Ca2+-binding properties of non-activated phosphorylase kinase. The calcium binding properties of non-activated phosphorylase kinase at pH 6.8 have been studied by the gel filtration technique at calcium concentrations from 50 nM to 50 muM. Taking into account the subunit structure alpha4beta4gamma4 the enzyme binds 12 mol Ca2+ per mol with an association constant of 6.0 X 10(7) M-1, 4 mol with an association constant of 1.7 X 10(6) M-1 and 36 mol with a binding constant of 3.9 X 10(4) M-1 at low ionic strength. In buffer of high ionic strength, i.e. 180 mM NH4Cl or 60 mM (NH4)2SO4, only a single set of eight binding sites with a binding constant of 5.5 X 10(7) M-1 is left. In a buffer containing 155 mM NH4Cl and 10 mM MgCl2, the calcium affinity of these sites is reduced to a KCa of 3.0 X 10(6) M-1, indicating competition between Ca2+ and Mg2+. From these measurements, the binding constant of Mg2+ for these sites is calculated to be 1.7 X 10(3) M-1 is left. In a buffer containing 155 mM NH4Cl and 10 mM MgCl2, the calcium affinity of these sites is reduced to a KCa of 3.0 X 10(6) M-1, indicating competition between Ca2+ and Mg2+. from these measurements, the binding constant of Mg2+ for these sites is calculated to be 1.7 X 10(3) M-1. Additionally, 10 mM Mg2+ induces a set of four new Ca2+ binding sites which show positive cooperativity. Their half-saturation constant under the conditions described is 3.5 X 10(5) M-1, and they, too, exhibit competition between Ca2+ and Mg2+. Since this set of sites is induced by Mg2+ a third group of binding sites for the latter metal must be postulated."}
{"id": "PMID:14006", "title": "Interactions of corticosterone, 5alpha-dihydrocorticosterone and dexamethasone with proteins in rat-liver cytosol.", "content": "The intracellular binding of [3H]corticosterone and [3H]dexamethasone and their metabolites to macromolecules in rat liver cytosol was studied in vivo and in vitro. The macromolecules binding corticosterone and its metabolites were characterized as (a) a steroid conjugate-binding (Stokes radius 2.5 nm and sedimentation coefficient 4.1 S in high ionic strength; pI 8.7, (b) transcortin and (c) a glucocorticoid \"receptor\". Competition experiments indicate that corticosterone and dexamethasone bind to the same site of the glucocorticoid receptor molecule. Different Stokes radii between the corticosterone-receptor and the dexamethasone-receptor complexes (6.9 and 6.3 nm, respectively, in high ionic strength) indicate that the two ligands induce different conformations of the receptor protein. This may be of importance when explaining the qualitative differences between the cellular effects of natural and synthetic glucocorticoids. 5alpha-Dihydrocorticosterone, on the other hand, competed to a very limited extent with dexamethasone for binding sites on the receptor. An assay of the inductive effect on liver tyrosine aminotransferase and tryptophan oxygenase indicated that 5alpha-dihydrocorticosterone was practically devoid of glucocorticoid activity. It is concluded that 5alpha-dihydrocorticosterone probably does not act as the mediator of corticosterone action in rat liver.", "contents": "Interactions of corticosterone, 5alpha-dihydrocorticosterone and dexamethasone with proteins in rat-liver cytosol. The intracellular binding of [3H]corticosterone and [3H]dexamethasone and their metabolites to macromolecules in rat liver cytosol was studied in vivo and in vitro. The macromolecules binding corticosterone and its metabolites were characterized as (a) a steroid conjugate-binding (Stokes radius 2.5 nm and sedimentation coefficient 4.1 S in high ionic strength; pI 8.7, (b) transcortin and (c) a glucocorticoid \"receptor\". Competition experiments indicate that corticosterone and dexamethasone bind to the same site of the glucocorticoid receptor molecule. Different Stokes radii between the corticosterone-receptor and the dexamethasone-receptor complexes (6.9 and 6.3 nm, respectively, in high ionic strength) indicate that the two ligands induce different conformations of the receptor protein. This may be of importance when explaining the qualitative differences between the cellular effects of natural and synthetic glucocorticoids. 5alpha-Dihydrocorticosterone, on the other hand, competed to a very limited extent with dexamethasone for binding sites on the receptor. An assay of the inductive effect on liver tyrosine aminotransferase and tryptophan oxygenase indicated that 5alpha-dihydrocorticosterone was practically devoid of glucocorticoid activity. It is concluded that 5alpha-dihydrocorticosterone probably does not act as the mediator of corticosterone action in rat liver."}
{"id": "PMID:14007", "title": "Studies by small-angle x-ray scattering of the quaternary structure of dissociation products of the beta-haemocyanin of Helix pomatia.", "content": "Helix pomatia beta-haemocyanin was split into dissociation products by varying the pH and the ionic strength. The purity of the solution was checked in an ultracentrifuge. Two defined dissociation products were studied in solution by small-angle X-ray scattering. In Tris-HC1 buffer, pH 8.0 and ionic strength 1 M, the following parameters of the dissociation product (tenths) could be determined: molecular weight = 7 x 10(5), volume = 1350 nm3, radius of gyration = 9.0 nm, maximal distance = 28.3 nm, radius of the spherical subunits about 2.6 nm, number of the subunits approximately 19. Tris-HC1 buffer, pH 8.7 and ionic strength 0.01 M, yielded dissociation products (twentieths) with the following parameters: molecular weight = 3.5 x 10(5), volume = 635 nm3, radius of gyration = 7.5 nm, maximal distance = 21.9 nm, radius of the spherical subunits about 2.5 nm. With this information, the assumption that the larger fragment was double the smaller one and the latest biochemical and morphological results, theoretical scattering curves of models were calculated and compared with the experimental curves. Two models are suggested which argee well with the dissociation products in radius of gyration and scattering.", "contents": "Studies by small-angle x-ray scattering of the quaternary structure of dissociation products of the beta-haemocyanin of Helix pomatia. Helix pomatia beta-haemocyanin was split into dissociation products by varying the pH and the ionic strength. The purity of the solution was checked in an ultracentrifuge. Two defined dissociation products were studied in solution by small-angle X-ray scattering. In Tris-HC1 buffer, pH 8.0 and ionic strength 1 M, the following parameters of the dissociation product (tenths) could be determined: molecular weight = 7 x 10(5), volume = 1350 nm3, radius of gyration = 9.0 nm, maximal distance = 28.3 nm, radius of the spherical subunits about 2.6 nm, number of the subunits approximately 19. Tris-HC1 buffer, pH 8.7 and ionic strength 0.01 M, yielded dissociation products (twentieths) with the following parameters: molecular weight = 3.5 x 10(5), volume = 635 nm3, radius of gyration = 7.5 nm, maximal distance = 21.9 nm, radius of the spherical subunits about 2.5 nm. With this information, the assumption that the larger fragment was double the smaller one and the latest biochemical and morphological results, theoretical scattering curves of models were calculated and compared with the experimental curves. Two models are suggested which argee well with the dissociation products in radius of gyration and scattering."}
{"id": "PMID:14008", "title": "Study of the role of puring phosphoribosyltransferases in the uptake of adenine and guanine by Schizosaccharomyces pombe cells.", "content": "1. In the yeast Schizosaccharomyces pombe 972h-, the uptake rate of both adenine and guanine is related to variations in the specific activity of the corresponding phosphoribosyltransferases during the growth of the culture. Furthermore, the mutant strains dap 1, devoid of adenine phosphoribosyltransferase activity, and pur 1, devoid of guanine phosphoribosyltransferase activity have a lowered uptake rate of adenine and guanine respectively, along with an increased apparent Km value for these purines in comparison to the wild-type 972h. 2. The uptake rate of the purines is strongly dependent on the pH of the uptake medium in 972h- as well as in the strains dap 1 and pur 1, the optimum being between pH4 and pH5. 3. A new method of extraction of 5-phosphoribosyl-1-pyrophosphate from the yeast has been devised. Important fluctuations of the P-Rib-P2 pool were measured in S. pombe at different stages of growth, the maximum taking place at the start of the exponential phase, whereas no variations in the specific activity of the P-Rib-P2 synthetase could be observed during the growth. The P-Rib-P2 intracellular content in the mutants devoid of purine phosphoribosyltransferases, namely pur 1, dap 1 and pur 1, dap 1, was increased up to 5-fold as compared to the wild-type strain. 4. The effect of intracellular concentrations of P-Rib-P2, a substrate for phosphoribosyltransferases, on the uptake rate of purines has been studied: addition of formycin to the growth medium lowered simultaneously the P-Rib-P2 intracellular content and the uptake of adenine and guanine. 5. Although our results demonstrate the activating effect of phosphoribosyltransferase activities on the uptake of adenine and guanine, they do not support the hypothesis of a 'group translocation' mechanism.", "contents": "Study of the role of puring phosphoribosyltransferases in the uptake of adenine and guanine by Schizosaccharomyces pombe cells. 1. In the yeast Schizosaccharomyces pombe 972h-, the uptake rate of both adenine and guanine is related to variations in the specific activity of the corresponding phosphoribosyltransferases during the growth of the culture. Furthermore, the mutant strains dap 1, devoid of adenine phosphoribosyltransferase activity, and pur 1, devoid of guanine phosphoribosyltransferase activity have a lowered uptake rate of adenine and guanine respectively, along with an increased apparent Km value for these purines in comparison to the wild-type 972h. 2. The uptake rate of the purines is strongly dependent on the pH of the uptake medium in 972h- as well as in the strains dap 1 and pur 1, the optimum being between pH4 and pH5. 3. A new method of extraction of 5-phosphoribosyl-1-pyrophosphate from the yeast has been devised. Important fluctuations of the P-Rib-P2 pool were measured in S. pombe at different stages of growth, the maximum taking place at the start of the exponential phase, whereas no variations in the specific activity of the P-Rib-P2 synthetase could be observed during the growth. The P-Rib-P2 intracellular content in the mutants devoid of purine phosphoribosyltransferases, namely pur 1, dap 1 and pur 1, dap 1, was increased up to 5-fold as compared to the wild-type strain. 4. The effect of intracellular concentrations of P-Rib-P2, a substrate for phosphoribosyltransferases, on the uptake rate of purines has been studied: addition of formycin to the growth medium lowered simultaneously the P-Rib-P2 intracellular content and the uptake of adenine and guanine. 5. Although our results demonstrate the activating effect of phosphoribosyltransferase activities on the uptake of adenine and guanine, they do not support the hypothesis of a 'group translocation' mechanism."}
{"id": "PMID:14009", "title": "Modification of the adrenal stress response by age and prior experience.", "content": "The adrenal stress response was examined in young and mature rats of both sexes by measuring the increase in adrenal tyrosine hydroxylase activity and serum corticosterone following exposure to electric footshock. Exposure to electric footshock for six minutes on three consecutive days elevated tyrosine hydroxylase activity in young and mature female rats and in young male rats, but failed to elevate enzyme activity in mature male animals. This decreased responsiveness of tyrosine hydroxylase in mature male rats could be overcome by giving prior experience with electric footshock. Age, sex, and prior experience interacted a affecting the levels of serum corticosterone in response to a three minute exposure to electric footshock. However, the most dramatic effect was due to prior experience, which reduced themagnitude and altered the time of the peak serum corticosterone response. These data demonstrated that the pituitary-adrenal system can be modified in old animals in a manner similar to the modification seen following infant stimulation, and indicate that several mechanisms may be invilved in the maturation and aging of a species.", "contents": "Modification of the adrenal stress response by age and prior experience. The adrenal stress response was examined in young and mature rats of both sexes by measuring the increase in adrenal tyrosine hydroxylase activity and serum corticosterone following exposure to electric footshock. Exposure to electric footshock for six minutes on three consecutive days elevated tyrosine hydroxylase activity in young and mature female rats and in young male rats, but failed to elevate enzyme activity in mature male animals. This decreased responsiveness of tyrosine hydroxylase in mature male rats could be overcome by giving prior experience with electric footshock. Age, sex, and prior experience interacted a affecting the levels of serum corticosterone in response to a three minute exposure to electric footshock. However, the most dramatic effect was due to prior experience, which reduced themagnitude and altered the time of the peak serum corticosterone response. These data demonstrated that the pituitary-adrenal system can be modified in old animals in a manner similar to the modification seen following infant stimulation, and indicate that several mechanisms may be invilved in the maturation and aging of a species."}
{"id": "PMID:14010", "title": "Relationship between plasma concentrations and pharmacological effects of labetalol.", "content": "In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.", "contents": "Relationship between plasma concentrations and pharmacological effects of labetalol. In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs."}
{"id": "PMID:14011", "title": "Beta-adrenoceptor blocking and electrophysiological effects of bufetolol in the guinea pig atria.", "content": "The potency of blockade of bufetolol, a beta-adrenoceptor blocking drug, and effects of bufetolol on the action potential, contractile force and various electrophysiological properties of the atrium were investigated in comparison with propranolol and quinidine. Bufetolol had a pA2 of 8.65 against the positive chronotropic action of isoproternol on the guinea pig sinus node. Bufetolol, 10(-7) g/ml, did not affect the action potential of the atrial muscle, while the drug, 3 X 10(-5) g/ml, significantly decreased the overshoot potential, the amplitude and the maximum rate of rise of the action potential and prolonged the times for 50% and 90% repolarization. The contractile force was reduced by bufetol, 3 X 10(-5) g/ml. The maximum responsive frequency to the driving stimulus was decreased by bufetol, 3 X 10(-5) g/ml.  The excitability of the muscle membrane was suppressed by bufetolo, 3 X 10(-5) g/ml, as indicated by changes in membrane responsiveness, membrane reactivation and strength-duration curve. Propranolol, 10(-5) g/ml and quinidine, 10(-5) g/ml showed similar effects on excitability. The authors suggest that these effects of bufetolol are responsible for its antidyshythmic effects.", "contents": "Beta-adrenoceptor blocking and electrophysiological effects of bufetolol in the guinea pig atria. The potency of blockade of bufetolol, a beta-adrenoceptor blocking drug, and effects of bufetolol on the action potential, contractile force and various electrophysiological properties of the atrium were investigated in comparison with propranolol and quinidine. Bufetolol had a pA2 of 8.65 against the positive chronotropic action of isoproternol on the guinea pig sinus node. Bufetolol, 10(-7) g/ml, did not affect the action potential of the atrial muscle, while the drug, 3 X 10(-5) g/ml, significantly decreased the overshoot potential, the amplitude and the maximum rate of rise of the action potential and prolonged the times for 50% and 90% repolarization. The contractile force was reduced by bufetol, 3 X 10(-5) g/ml. The maximum responsive frequency to the driving stimulus was decreased by bufetol, 3 X 10(-5) g/ml.  The excitability of the muscle membrane was suppressed by bufetolo, 3 X 10(-5) g/ml, as indicated by changes in membrane responsiveness, membrane reactivation and strength-duration curve. Propranolol, 10(-5) g/ml and quinidine, 10(-5) g/ml showed similar effects on excitability. The authors suggest that these effects of bufetolol are responsible for its antidyshythmic effects."}
{"id": "PMID:14012", "title": "Aminotetralins as selective beta-adrenergic agonists.", "content": "Aminotetralin derivatives M-8 and JOD-176, were studied in relation to isoproterenol for beta-adrenergic activity. M-8 and JOD-176 were found to be very weak in activating cardiac beta-receptors. These compounds were also found to be considerably more active in uterine and bronchial smooth muscle. Because these compounds were also shown to be very inactive in vascular smooth muscle, the possibility that beta-receptors in different smooth muscle types may also differ was suggested.", "contents": "Aminotetralins as selective beta-adrenergic agonists. Aminotetralin derivatives M-8 and JOD-176, were studied in relation to isoproterenol for beta-adrenergic activity. M-8 and JOD-176 were found to be very weak in activating cardiac beta-receptors. These compounds were also found to be considerably more active in uterine and bronchial smooth muscle. Because these compounds were also shown to be very inactive in vascular smooth muscle, the possibility that beta-receptors in different smooth muscle types may also differ was suggested."}
{"id": "PMID:14020", "title": "\"Direct\" effect of reserpine on various preparations.", "content": "The action of reserpine added to the bathing solution has been studied in isolated organs, examining various kinds of receptor systems and biological preparations. The investigation has been comparatively carried out in normal and reserpine-pretreated animals. The most important effect of reserpine is the inhibition of the maximum response to noradrenalin in the rat vas deferens, and the inhibition of response to furtrethonium and histamine in the intestine of rat and guinea-pig, respectively. This affect appears to be independent of the release of catecholamines, and is therefore direct, aspecific and similar to the non-competitive effect of papaverine.", "contents": "\"Direct\" effect of reserpine on various preparations. The action of reserpine added to the bathing solution has been studied in isolated organs, examining various kinds of receptor systems and biological preparations. The investigation has been comparatively carried out in normal and reserpine-pretreated animals. The most important effect of reserpine is the inhibition of the maximum response to noradrenalin in the rat vas deferens, and the inhibition of response to furtrethonium and histamine in the intestine of rat and guinea-pig, respectively. This affect appears to be independent of the release of catecholamines, and is therefore direct, aspecific and similar to the non-competitive effect of papaverine."}
{"id": "PMID:14035", "title": "[The histaminergic mechanisms in the regulation of prolactin secretion in urethan-anesthetized rats (author's transl)].", "content": "In an attempt to detect the existence of histaminergic mechanisms in the regulation of prolactin secretion in rats, the effects of histidine and histamine-receptor antagonists (chlorpheniramine and metiamide) on plasma prolactin levels in urethan-anesthetized rats were investigated in relation to other aminergic mechanisms. Chlorpheniramine was used as an H1-receptor antagonist and metiamide as an H2-receptor antagonist. Wistar male rats were used under urethan anesthesia and blood was obtained by cardiac puncture. Rat plasma prolactin was measured by radioimmunoassay. As already reported, L-DOPA and diethyldithiocarbamate markedly decreased plasma prolactin levels in rats. Dihydroxyphenylserine increased prolactin levels. Brocresine phosphate, a histidine decarboxylase inhibitor, markedly stimulated prolactin secretion in urethan-anesthetized rats. This stimulation was not blocked by pretreatment with histidine or L-DOPA. Histidine alone did not affect plasma levels of prolactin or methyldopamine-induced increase in plasma prolactin levels. On the other hand, histidine significantly stimulated prolactin secretion in chlorpheniramine-treated rats. In contrast, histidine depressed plasma prolactin levels in metiamide-treated rats. These findings indicate that a dopaminergic component is inhibitory and a noradrenergic one is stimulatory in prolactin secretion in rats and further that there exist the histaminergic mechanisms, relatively independent from other aminergic mechanisms, which might also play an important role in the regulation of prolactin secretion in rats. Furthermore, it is suggested that H1-receptor is stimulatory and H2-receptor is inhibitory in prolactin secretion in rats.", "contents": "[The histaminergic mechanisms in the regulation of prolactin secretion in urethan-anesthetized rats (author's transl)]. In an attempt to detect the existence of histaminergic mechanisms in the regulation of prolactin secretion in rats, the effects of histidine and histamine-receptor antagonists (chlorpheniramine and metiamide) on plasma prolactin levels in urethan-anesthetized rats were investigated in relation to other aminergic mechanisms. Chlorpheniramine was used as an H1-receptor antagonist and metiamide as an H2-receptor antagonist. Wistar male rats were used under urethan anesthesia and blood was obtained by cardiac puncture. Rat plasma prolactin was measured by radioimmunoassay. As already reported, L-DOPA and diethyldithiocarbamate markedly decreased plasma prolactin levels in rats. Dihydroxyphenylserine increased prolactin levels. Brocresine phosphate, a histidine decarboxylase inhibitor, markedly stimulated prolactin secretion in urethan-anesthetized rats. This stimulation was not blocked by pretreatment with histidine or L-DOPA. Histidine alone did not affect plasma levels of prolactin or methyldopamine-induced increase in plasma prolactin levels. On the other hand, histidine significantly stimulated prolactin secretion in chlorpheniramine-treated rats. In contrast, histidine depressed plasma prolactin levels in metiamide-treated rats. These findings indicate that a dopaminergic component is inhibitory and a noradrenergic one is stimulatory in prolactin secretion in rats and further that there exist the histaminergic mechanisms, relatively independent from other aminergic mechanisms, which might also play an important role in the regulation of prolactin secretion in rats. Furthermore, it is suggested that H1-receptor is stimulatory and H2-receptor is inhibitory in prolactin secretion in rats."}
{"id": "PMID:14037", "title": "Chromosomal breakage in systemic sclerosis and related disorders.", "content": "Chromosome aberrations such as gaps and breaks of one or both chromatids, acentric fragments, dicentrics, ring chromosomes and other abnormal chromosomes are observed in lymphocyte and fibroblast cultures as well as in direct bone marrow preparations from patients with systemic sclerosis. A serum factor producing chromosome breaks in mitoses from healthy donors was observed in 37 of 42 scleroderma patients. The biochemical nature of this breakage factor is still undefined. Increased breakage is also noted in a high percentage of healthy family members of scleroderma patients. It is also a common feature of related disorders such as lupus erythematosus, dermatomyositis, periarteritis nodosa and rheumatoid arthritis. An increase in chromosome breaks and rearrangements is also present in NZB mice developing spontaneously an autoimmune disorder that has been extensively studied by workers interested in lupus erythematosus. The similarity of the cytogenetic findings provides the opportunity to use these mice as an experimental model to investigate relationships between immunological perturbations and chromosomal aberrations.", "contents": "Chromosomal breakage in systemic sclerosis and related disorders. Chromosome aberrations such as gaps and breaks of one or both chromatids, acentric fragments, dicentrics, ring chromosomes and other abnormal chromosomes are observed in lymphocyte and fibroblast cultures as well as in direct bone marrow preparations from patients with systemic sclerosis. A serum factor producing chromosome breaks in mitoses from healthy donors was observed in 37 of 42 scleroderma patients. The biochemical nature of this breakage factor is still undefined. Increased breakage is also noted in a high percentage of healthy family members of scleroderma patients. It is also a common feature of related disorders such as lupus erythematosus, dermatomyositis, periarteritis nodosa and rheumatoid arthritis. An increase in chromosome breaks and rearrangements is also present in NZB mice developing spontaneously an autoimmune disorder that has been extensively studied by workers interested in lupus erythematosus. The similarity of the cytogenetic findings provides the opportunity to use these mice as an experimental model to investigate relationships between immunological perturbations and chromosomal aberrations."}
{"id": "PMID:14038", "title": "Pilot open-label study of alprazolam (U-31,889) in anxious alcoholic out-patients.", "content": "Twenty out-patients suffering from anxiety and tension after withdrawal from alcohol were treated for 28 days with alprazolam. Three patients dropped out for intercurrent events, and 2 dropped out for recurrent drinking. Of the 15 patients completing the study, analysis of variance showed significant improvement in all Physician's Ratings as well as all patient self-ratings. At the 28th day, 93% of the patients rated moderate to marked improvement on the Physician's Global Impression and Therapeutic Effect, and 93% self rated at least a little better. Side-effects were generally mild and inconsequential. No adverse effects attributable to alprazolam were noted on laboratory evaluations, EKG's or ophthalmologic examinations.", "contents": "Pilot open-label study of alprazolam (U-31,889) in anxious alcoholic out-patients. Twenty out-patients suffering from anxiety and tension after withdrawal from alcohol were treated for 28 days with alprazolam. Three patients dropped out for intercurrent events, and 2 dropped out for recurrent drinking. Of the 15 patients completing the study, analysis of variance showed significant improvement in all Physician's Ratings as well as all patient self-ratings. At the 28th day, 93% of the patients rated moderate to marked improvement on the Physician's Global Impression and Therapeutic Effect, and 93% self rated at least a little better. Side-effects were generally mild and inconsequential. No adverse effects attributable to alprazolam were noted on laboratory evaluations, EKG's or ophthalmologic examinations."}
{"id": "PMID:14039", "title": "Diphenylpyraline (Lergobine) in the treatment of patients suffering from allergic and vasomotor rhinitis.", "content": "In a double-blind study, diphenylpyraline (Lergobine) was given to 63 patients whose main symptoms were stuffiness of the nose, increased secretion of mucus, snuffling, sneezing and redness of the eyes. Fifty-seven patients were given placebo for identical symptoms. Diphenylpyraline was found to have a better effect on all the symptoms than placebo. The difference was statistically significant in respect of the discharge of mucus and redness of the eyes, and when the total symptoms were considered as a whole. In atopic patients the better effect of diphenylpyraline was highly significant.", "contents": "Diphenylpyraline (Lergobine) in the treatment of patients suffering from allergic and vasomotor rhinitis. In a double-blind study, diphenylpyraline (Lergobine) was given to 63 patients whose main symptoms were stuffiness of the nose, increased secretion of mucus, snuffling, sneezing and redness of the eyes. Fifty-seven patients were given placebo for identical symptoms. Diphenylpyraline was found to have a better effect on all the symptoms than placebo. The difference was statistically significant in respect of the discharge of mucus and redness of the eyes, and when the total symptoms were considered as a whole. In atopic patients the better effect of diphenylpyraline was highly significant."}
{"id": "PMID:14040", "title": "A follow-up study of the use of benoral tablets in non-articular rheumatism.", "content": "A multicentric follow-up study was conducted in general practice to assess disease characteristics which determine analgesic needs in non-articular rheumatism. Of 127 patients studied, those with chronic conditions such as brachial fibrositis and tennis elbow with a history extending over more than a month tended to require a longer course of treatment than those whose symptoms related to muscles of the trunk and spine. For most patients a one or two week course of Benoral tablets proved adequate in length and efficacy.", "contents": "A follow-up study of the use of benoral tablets in non-articular rheumatism. A multicentric follow-up study was conducted in general practice to assess disease characteristics which determine analgesic needs in non-articular rheumatism. Of 127 patients studied, those with chronic conditions such as brachial fibrositis and tennis elbow with a history extending over more than a month tended to require a longer course of treatment than those whose symptoms related to muscles of the trunk and spine. For most patients a one or two week course of Benoral tablets proved adequate in length and efficacy."}
{"id": "PMID:14041", "title": "Comparison of the in vitro conversion of estradiol-17 beta to estrone of normal and neoplastic human breast tissue.", "content": "Specific activity  of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was measured in 48 tissue specimens of human female breast cancer and, in addition, 48 nonmalignant tissue specimens obtained in each case from the same cancer-bearing breast. In all cases the nonmalignant tissue showed greater conversion of estradiol-17 beta into estrone than the neoplastic tissues. In normal human breast tissue of premenopausal women specific enzyme activity depended on the phase of the MENSTRUAL CYCLE: the highest values of 17 beta-HSD activity were found in the early secretory phase. To determine the intracellular distribution of the 17 beta-HSD, purified microsomes, mitochondria, peroxysomes, lysosomes, nuclei and cytosol fractions were prepared. The purity of each fraction was monitored by marker enzymes. It was found that the 17 beta-HSD was mainly located in mitochondria and microsomes. Furthermore it could be demonstrated that the microsomal enzyme was bound tightly to the membranes of the endoplasmic reticulum, while the mitochondrial 17 beta-HSD was mainly associated with the outer membranes of the organelle. Kinetic parameters (Km-values, coenzyme requirements and maximal velocities) of a cytoplasmic, nuclear, mitochondrial and microsomal 17 beta-HSD of normal and neoplastic human mammary tissue were compared. Maximal velocity was highest in enzyme preparations of normal mammary tissue obtained from premenopausal women in the early secretory phase. Km-values wrere nearly identical in normal and neoplastic mammary tissue preparations (approx. 1 X 10(-6) M). NAD was more efficient than NADP as a cofactor. For the conversion of estradiol to estrone the optimum temperature was approximately 40 degrees C and the optimum pH 9.5. For the reduction of estrone the optimum pH was 6.5. Sulphydryl groups were shown to be essential for catalysis.", "contents": "Comparison of the in vitro conversion of estradiol-17 beta to estrone of normal and neoplastic human breast tissue. Specific activity  of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was measured in 48 tissue specimens of human female breast cancer and, in addition, 48 nonmalignant tissue specimens obtained in each case from the same cancer-bearing breast. In all cases the nonmalignant tissue showed greater conversion of estradiol-17 beta into estrone than the neoplastic tissues. In normal human breast tissue of premenopausal women specific enzyme activity depended on the phase of the MENSTRUAL CYCLE: the highest values of 17 beta-HSD activity were found in the early secretory phase. To determine the intracellular distribution of the 17 beta-HSD, purified microsomes, mitochondria, peroxysomes, lysosomes, nuclei and cytosol fractions were prepared. The purity of each fraction was monitored by marker enzymes. It was found that the 17 beta-HSD was mainly located in mitochondria and microsomes. Furthermore it could be demonstrated that the microsomal enzyme was bound tightly to the membranes of the endoplasmic reticulum, while the mitochondrial 17 beta-HSD was mainly associated with the outer membranes of the organelle. Kinetic parameters (Km-values, coenzyme requirements and maximal velocities) of a cytoplasmic, nuclear, mitochondrial and microsomal 17 beta-HSD of normal and neoplastic human mammary tissue were compared. Maximal velocity was highest in enzyme preparations of normal mammary tissue obtained from premenopausal women in the early secretory phase. Km-values wrere nearly identical in normal and neoplastic mammary tissue preparations (approx. 1 X 10(-6) M). NAD was more efficient than NADP as a cofactor. For the conversion of estradiol to estrone the optimum temperature was approximately 40 degrees C and the optimum pH 9.5. For the reduction of estrone the optimum pH was 6.5. Sulphydryl groups were shown to be essential for catalysis."}
{"id": "PMID:14042", "title": "Back-diffusion--fact or fiction?", "content": "Alterations in the concentration of acid in gastric juice secreted at different flow rates and disappearance of acid from the gastric lumen, when the gastric mucosa is exposed to acid luminal contents, have been interpreted as indicating \"back-diffusion\" of acid into the gastric mucosa from the luminal contents. The loss of acid from the gastric contents increases when the mucosa is exposed to certain drugs or is diseased, giving rise to the suggestion that the increased degree of \"back-diffusion\" of acid indicates mucosal damage, reflecting a breakdown of the gastric mucosal \"barrier\" to back-diffusion of acid from the gastric lumen. The change in the \"barrier\" properties of the gastric mucosa has been found to be associated with change in the electrical properties of the mucosa, so that alterations of the transmucosal potential difference has been considered to denote gastric mucosal damage. The case for every one of these hypotheses and for their underlying assumptions is discussed and found wanting for lack of direct evidence.", "contents": "Back-diffusion--fact or fiction? Alterations in the concentration of acid in gastric juice secreted at different flow rates and disappearance of acid from the gastric lumen, when the gastric mucosa is exposed to acid luminal contents, have been interpreted as indicating \"back-diffusion\" of acid into the gastric mucosa from the luminal contents. The loss of acid from the gastric contents increases when the mucosa is exposed to certain drugs or is diseased, giving rise to the suggestion that the increased degree of \"back-diffusion\" of acid indicates mucosal damage, reflecting a breakdown of the gastric mucosal \"barrier\" to back-diffusion of acid from the gastric lumen. The change in the \"barrier\" properties of the gastric mucosa has been found to be associated with change in the electrical properties of the mucosa, so that alterations of the transmucosal potential difference has been considered to denote gastric mucosal damage. The case for every one of these hypotheses and for their underlying assumptions is discussed and found wanting for lack of direct evidence."}
{"id": "PMID:14043", "title": "Effect of cimetidine on lower esophageal sphincter pressure, intragastric pH and serum levels of immunoreactive gastrin in man.", "content": "The influence of cimetidine on the lower esophageal sphincter, the intragastric pH and the serum levels of immunoreactive gastrin was investigated in eight volunteers and compared with a control group. After oral application of 400 mg cimetidine, the intragastric pH rose from 1.7 +/- 0.13 to 6.2 +/- 0.4 and the lower esophageal sphincter pressure increased slightly but significantly from 15.6 +/- 1.1 to 22.7 +/- 1.8 mm Hg after 20 min and to 25.8 +/- 2.0 after 30 min, respectively. At the same time the serum immunoreactive gastrin levels did not change. A direct effect of cimetinidine on the lower esophageal sphincter or an indirect effect via gastric alkalinization is discussed.", "contents": "Effect of cimetidine on lower esophageal sphincter pressure, intragastric pH and serum levels of immunoreactive gastrin in man. The influence of cimetidine on the lower esophageal sphincter, the intragastric pH and the serum levels of immunoreactive gastrin was investigated in eight volunteers and compared with a control group. After oral application of 400 mg cimetidine, the intragastric pH rose from 1.7 +/- 0.13 to 6.2 +/- 0.4 and the lower esophageal sphincter pressure increased slightly but significantly from 15.6 +/- 1.1 to 22.7 +/- 1.8 mm Hg after 20 min and to 25.8 +/- 2.0 after 30 min, respectively. At the same time the serum immunoreactive gastrin levels did not change. A direct effect of cimetinidine on the lower esophageal sphincter or an indirect effect via gastric alkalinization is discussed."}
{"id": "PMID:14044", "title": "Effects of posture on gastro-oesophageal reflux.", "content": "Continuous oesophageal pH measurements have been used to assess the influence of posture (lying, sitting, bed-up) on gastro-oesophageal reflux. The percentage of time during which oesophageal pH was below 5 and the number of reflux episodes was significantly reduced when patients were in bed-up position than when sitting or lying. There was no significant difference when sitting and lying positions were compared. The results suggest that by adopting the bed-up position (elevation of the head end of the bed with blocks of 28 cm), the patient will have a symptomatic benefit, the frequency of reflux is decreased, and acid clearing is improved.", "contents": "Effects of posture on gastro-oesophageal reflux. Continuous oesophageal pH measurements have been used to assess the influence of posture (lying, sitting, bed-up) on gastro-oesophageal reflux. The percentage of time during which oesophageal pH was below 5 and the number of reflux episodes was significantly reduced when patients were in bed-up position than when sitting or lying. There was no significant difference when sitting and lying positions were compared. The results suggest that by adopting the bed-up position (elevation of the head end of the bed with blocks of 28 cm), the patient will have a symptomatic benefit, the frequency of reflux is decreased, and acid clearing is improved."}
{"id": "PMID:14045", "title": "Effect of cimetidine on gastric mucosal histamine and histidine decarboxylase activity in rats.", "content": "In conscious rats and in anaesthetized gastric fistula rats, the effects of low and high doses of the histamine H2-receptor antagonist cimetidine was studied on gastric mucosal histamine concentration and histidine decarboxylase activity with or without concomitant administration of pentagastrin. In conscious animals a singleinjection of pentagastrin reduced gastric mucosal histamine concentration and elevated histidine decarboxylase activity. This effect was not antagonized by low doses of cimetidine. High doses of cimetidine, like pentagastrin, reduced the histamine concentration and elevated the histidine decarboxylase activity. In anaesthetized rats low doses of cimetidine and reduced gastric acid secretion. The effects of cimetidine on gastric mucosal histamine and histidine decarboxylase were less pronounced than in conscious animals. The histidine decarboxylase stimulating activity of high doses of cimetidine was not abolished by gastric perfusion with acid suggesting that endogenously released gastrin is not involved. A feedback relationship between the blockade of the target organ and increased histamine biosynthesis is discussed.", "contents": "Effect of cimetidine on gastric mucosal histamine and histidine decarboxylase activity in rats. In conscious rats and in anaesthetized gastric fistula rats, the effects of low and high doses of the histamine H2-receptor antagonist cimetidine was studied on gastric mucosal histamine concentration and histidine decarboxylase activity with or without concomitant administration of pentagastrin. In conscious animals a singleinjection of pentagastrin reduced gastric mucosal histamine concentration and elevated histidine decarboxylase activity. This effect was not antagonized by low doses of cimetidine. High doses of cimetidine, like pentagastrin, reduced the histamine concentration and elevated the histidine decarboxylase activity. In anaesthetized rats low doses of cimetidine and reduced gastric acid secretion. The effects of cimetidine on gastric mucosal histamine and histidine decarboxylase were less pronounced than in conscious animals. The histidine decarboxylase stimulating activity of high doses of cimetidine was not abolished by gastric perfusion with acid suggesting that endogenously released gastrin is not involved. A feedback relationship between the blockade of the target organ and increased histamine biosynthesis is discussed."}
{"id": "PMID:14046", "title": "Glutamine synthetase induction in embryonic neural retina. Interactions of receptor-hydrocortisone complexes with cell nuclei.", "content": "In the neural retina of the chick embryo, hydrocortisone (HC) elicits differential gene expression resulting in the induction of glutamine synthetase (GS), which is an enzyme marker of differentiation in the retina. The relationship between nuclear binding of receptor-hydrocortisone (R-HC) complexes and GS induction was investigated in cultures of retina tissue from 12-day chick embryos. The number of HC binding sites in the cytoplasm was estimated as 1650+/-200 per retina cell; there are approximately 1500+/-100 acceptor sites for R-HC per retina nucleus. GS induction in the retina became detectable only after R-HC bound to more than 40% of the nuclear acceptors sites; increased binding coincided with higher induction levels, until complete site saturation was attained; Proflavine, which blocks preferentially and completely GS induction in the retina by interfering in the nucleus with the enzyme-inducing action of the hormone, reduced nuclear binding of R-HC by only 20%; thus, only part of the R-HC that binds in the nucleus appears to be directly involved in eliciting the induction of GS. Within one hour after exposure of the retina to an inducing dose of HC, there was translocation of HC and HC-receptors (as R-HC complexes) from the cytoplasm into the nucleus and saturation of nuclear accepegan to decline; in 12 h, it was reduced to 50% of the initial saturation level. Since, during this time, the enzyme activity to increase, persistence of the induced state depends on association of the hormone with only a portion of the sites in the nucleus to which it can bind. The decrease in the amount of bound HC in the nuclei of induced cells was accompanied by an increase in the level of HC receptors in the cytoplasm. About 50% of this increase could be prevented by cycloheximide; this suggests that the reappearance of HC receptors in the cell cytoplasm may be due, at least in part, to de novo synthesis of HC receptors.", "contents": "Glutamine synthetase induction in embryonic neural retina. Interactions of receptor-hydrocortisone complexes with cell nuclei. In the neural retina of the chick embryo, hydrocortisone (HC) elicits differential gene expression resulting in the induction of glutamine synthetase (GS), which is an enzyme marker of differentiation in the retina. The relationship between nuclear binding of receptor-hydrocortisone (R-HC) complexes and GS induction was investigated in cultures of retina tissue from 12-day chick embryos. The number of HC binding sites in the cytoplasm was estimated as 1650+/-200 per retina cell; there are approximately 1500+/-100 acceptor sites for R-HC per retina nucleus. GS induction in the retina became detectable only after R-HC bound to more than 40% of the nuclear acceptors sites; increased binding coincided with higher induction levels, until complete site saturation was attained; Proflavine, which blocks preferentially and completely GS induction in the retina by interfering in the nucleus with the enzyme-inducing action of the hormone, reduced nuclear binding of R-HC by only 20%; thus, only part of the R-HC that binds in the nucleus appears to be directly involved in eliciting the induction of GS. Within one hour after exposure of the retina to an inducing dose of HC, there was translocation of HC and HC-receptors (as R-HC complexes) from the cytoplasm into the nucleus and saturation of nuclear accepegan to decline; in 12 h, it was reduced to 50% of the initial saturation level. Since, during this time, the enzyme activity to increase, persistence of the induced state depends on association of the hormone with only a portion of the sites in the nucleus to which it can bind. The decrease in the amount of bound HC in the nuclei of induced cells was accompanied by an increase in the level of HC receptors in the cytoplasm. About 50% of this increase could be prevented by cycloheximide; this suggests that the reappearance of HC receptors in the cell cytoplasm may be due, at least in part, to de novo synthesis of HC receptors."}
{"id": "PMID:14047", "title": "Changes in the antral mucosal pepsin in dogs with chronic ulcer: pathogenesis of cinchophen ulcer.", "content": "All of the dogs given continuous injection of 100 mg/kg sodium cinchophen for 21 days developed chronic ulcers in the pyloric portion of the stomach. Those dogs given cinchophen exhibited a definite increase in gastric pepsin secretion. Readings of gastric mucosal pepsinogen showed a significant high concentration both in the fundic and pyloric gland area in the cinchophen-treated animals. As the injections were continued, the gastric mucosa-juice peptic activity ratio (MJPR) in the fundic gland area become low. These results do not point to pathological changes in the fundic gland area. The mean pH value of the surface of antral mucosa varied greatly from dog to dog and was slightly higher than normal. In the dog which had chronic ulcers in the antral portion, the antral mucosal pepsinogen concentration become eight times higher than that seen in the control animals. The incidence and chronicity of the cinchophen gastric ulcers were related to the local pepsin increase adjacent to the lesions. The origin of pepsin which appeared in the antral mucosa and cinchophen ulcerogenesis were discussed.", "contents": "Changes in the antral mucosal pepsin in dogs with chronic ulcer: pathogenesis of cinchophen ulcer. All of the dogs given continuous injection of 100 mg/kg sodium cinchophen for 21 days developed chronic ulcers in the pyloric portion of the stomach. Those dogs given cinchophen exhibited a definite increase in gastric pepsin secretion. Readings of gastric mucosal pepsinogen showed a significant high concentration both in the fundic and pyloric gland area in the cinchophen-treated animals. As the injections were continued, the gastric mucosa-juice peptic activity ratio (MJPR) in the fundic gland area become low. These results do not point to pathological changes in the fundic gland area. The mean pH value of the surface of antral mucosa varied greatly from dog to dog and was slightly higher than normal. In the dog which had chronic ulcers in the antral portion, the antral mucosal pepsinogen concentration become eight times higher than that seen in the control animals. The incidence and chronicity of the cinchophen gastric ulcers were related to the local pepsin increase adjacent to the lesions. The origin of pepsin which appeared in the antral mucosa and cinchophen ulcerogenesis were discussed."}
{"id": "PMID:14048", "title": "Carcinoembryonic character of gamma-glutamyltranspeptidase in primary hepatocellular carcinoma.", "content": "As a characteristic isoenzyme of gamma-glutamyl transpeptidase (gamma-GTP) has been detected in sera of patients with primary hepatocellular carcinoma, which migrates to alpha-globulin region on polyacrylamide-gel electrophoresis, biochemical studies on human fetal liver, Morris hepatoma (7316-A, 7794-A), and human hepatoma was carried out to elucidate its carcinoembryonic character. The highest distribution of the enzyme was found in particle fraction of human fetal liver as well as of Morris hepatoma, and an isoenzyme of gamma-GTP with the same electrophoretic mobility as detected in human hepatoma was obtained, which reflected to the pattern of the serum zymograms. Histochemically, the enzyme was distributed in plasma membrane of the fetal hepatocytes and Morris hepatoma cells, while it was distributed diffusely throughout the cytoplasm of human hepatoma cells. These findings may strongly suggest that gamma-GTP in hepatoma has a carcinoembryonic character and the detection of a serum isoenzyme in the alpha-globulin region is a quite diagnostic as well as the detection of alpha-fetoprotein in the field of neoplasma of the liver. The physicochemical and kinetic properties of the enzyme in human hepatoma were also discussed.", "contents": "Carcinoembryonic character of gamma-glutamyltranspeptidase in primary hepatocellular carcinoma. As a characteristic isoenzyme of gamma-glutamyl transpeptidase (gamma-GTP) has been detected in sera of patients with primary hepatocellular carcinoma, which migrates to alpha-globulin region on polyacrylamide-gel electrophoresis, biochemical studies on human fetal liver, Morris hepatoma (7316-A, 7794-A), and human hepatoma was carried out to elucidate its carcinoembryonic character. The highest distribution of the enzyme was found in particle fraction of human fetal liver as well as of Morris hepatoma, and an isoenzyme of gamma-GTP with the same electrophoretic mobility as detected in human hepatoma was obtained, which reflected to the pattern of the serum zymograms. Histochemically, the enzyme was distributed in plasma membrane of the fetal hepatocytes and Morris hepatoma cells, while it was distributed diffusely throughout the cytoplasm of human hepatoma cells. These findings may strongly suggest that gamma-GTP in hepatoma has a carcinoembryonic character and the detection of a serum isoenzyme in the alpha-globulin region is a quite diagnostic as well as the detection of alpha-fetoprotein in the field of neoplasma of the liver. The physicochemical and kinetic properties of the enzyme in human hepatoma were also discussed."}
{"id": "PMID:14049", "title": "Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.", "content": "A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy.", "contents": "Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy."}
{"id": "PMID:14050", "title": "Heartburn of pregnancy.", "content": "Lower esophageal sphincter pressure, basal gastric pH, fasting plasma gastrin, and plasma concentrations of estrone, estradiol, and progesterone were measured in pregnant volunteers at 12, 24, and 36 weeks of gestation, and again at 1 to 4 weeks postpartum. In addition, basal and pentagastrin-stimulated acid secretory responses at each time were measured. No differences in basal gastric pH, basal, and peak acid outputs were observed during pregnancy when compared to the postpartum values. In contrast, lower esophageal sphincter pressure was reduced at all times during pregnancy, reaching a nadir at 36 weeks. Postpartum lower esophageal pressures were normal. As expected, plasma concentrations of progesterone and both estrogens increased progressively during pregnancy. These data are consistent with earlier studies in women ingesting oral contraceptives. Moreover, they provide support for the thesis that the progressive increase in plasma progesterone alone or in combination with estrogens that occurs during pregnancy is responsible for the reduction of lower esophageal sphincter pressure which allows esophageal reflux to occur with the resultant development of symptomatic heartburn.", "contents": "Heartburn of pregnancy. Lower esophageal sphincter pressure, basal gastric pH, fasting plasma gastrin, and plasma concentrations of estrone, estradiol, and progesterone were measured in pregnant volunteers at 12, 24, and 36 weeks of gestation, and again at 1 to 4 weeks postpartum. In addition, basal and pentagastrin-stimulated acid secretory responses at each time were measured. No differences in basal gastric pH, basal, and peak acid outputs were observed during pregnancy when compared to the postpartum values. In contrast, lower esophageal sphincter pressure was reduced at all times during pregnancy, reaching a nadir at 36 weeks. Postpartum lower esophageal pressures were normal. As expected, plasma concentrations of progesterone and both estrogens increased progressively during pregnancy. These data are consistent with earlier studies in women ingesting oral contraceptives. Moreover, they provide support for the thesis that the progressive increase in plasma progesterone alone or in combination with estrogens that occurs during pregnancy is responsible for the reduction of lower esophageal sphincter pressure which allows esophageal reflux to occur with the resultant development of symptomatic heartburn."}
{"id": "PMID:14051", "title": "Acid secretion and serum gastrin at graded intragasric pressures in man.", "content": "In 16 healthy subjects, gastric distention was produced by infusion of 5% mannitol solution, pH 5.5. Constant intragastric pressure was maintained by use of a barostat. Over successive 1-hr periods the head of pressure was raised in 5-cm increments from an arbitrary zero point to 15 cm. Gastric acid secretion was measured by constant intragastric titration. Blood samples were obtained throughout the study for measurement of serum gastrin concentrations. When intragastric pressure was raised from zero to 5 cm H2O, gastric acid secretion increased significantly (24% of peak acid response to pentagastrin). Acid responses at 10 and 15 cm pressure were lower. Serum gastrin concentrations increased slightly at 15 cm pressure but not at 5 or 10 cm. There was no correlation between increments in serum gastrin and acid secretory rates. We conclude that gastric distention at low pressures stimulated acid secretion by a mechanism and did not involve increases in circulating gastrin concentrations. Slight increases in serum gastrin observed at the highest distending pressure were not associated with further increases in acid secretion.", "contents": "Acid secretion and serum gastrin at graded intragasric pressures in man. In 16 healthy subjects, gastric distention was produced by infusion of 5% mannitol solution, pH 5.5. Constant intragastric pressure was maintained by use of a barostat. Over successive 1-hr periods the head of pressure was raised in 5-cm increments from an arbitrary zero point to 15 cm. Gastric acid secretion was measured by constant intragastric titration. Blood samples were obtained throughout the study for measurement of serum gastrin concentrations. When intragastric pressure was raised from zero to 5 cm H2O, gastric acid secretion increased significantly (24% of peak acid response to pentagastrin). Acid responses at 10 and 15 cm pressure were lower. Serum gastrin concentrations increased slightly at 15 cm pressure but not at 5 or 10 cm. There was no correlation between increments in serum gastrin and acid secretory rates. We conclude that gastric distention at low pressures stimulated acid secretion by a mechanism and did not involve increases in circulating gastrin concentrations. Slight increases in serum gastrin observed at the highest distending pressure were not associated with further increases in acid secretion."}
{"id": "PMID:14056", "title": "Diurnal variations in the pH of pathological gallbladder bile.", "content": "The pH of gallbladder and common duct bile from patients undergoing surgery for cholecystectomy has been measured. The bile was collected and kept anaerobically at 37 degrees C, and the pH measured at 37 degrees C, generally within 30-60 minutes of the bile being taken from the patient. Only data from patients having functioning or poorly-functioning gallbladders were included in the calculations. The pH of common duct bile was always greater than that of the corresponding gallbladder bile, and the data available suggest that it does not vary diurnally. The mean pH of gallbladder bile from patients undergoing their operation at different times during the day shows a diurnal variation, the bile becoming more acidic with time. Furthermore, there is also a diurnal variation in the activity of the acidifying process. Data for the patients suggest this is retarded by sleep, inactivity, or lying down.", "contents": "Diurnal variations in the pH of pathological gallbladder bile. The pH of gallbladder and common duct bile from patients undergoing surgery for cholecystectomy has been measured. The bile was collected and kept anaerobically at 37 degrees C, and the pH measured at 37 degrees C, generally within 30-60 minutes of the bile being taken from the patient. Only data from patients having functioning or poorly-functioning gallbladders were included in the calculations. The pH of common duct bile was always greater than that of the corresponding gallbladder bile, and the data available suggest that it does not vary diurnally. The mean pH of gallbladder bile from patients undergoing their operation at different times during the day shows a diurnal variation, the bile becoming more acidic with time. Furthermore, there is also a diurnal variation in the activity of the acidifying process. Data for the patients suggest this is retarded by sleep, inactivity, or lying down."}
{"id": "PMID:14057", "title": "Sulphasalazine in asymptomatic Crohn's disease. A multicentre trial.", "content": "During a six year period 43 patients with Crohns disease were included in a double-blind controlled trial of sulphasalazine given for one year as a possible treatment for reducing the relapse rate after resection or in asymptomatic patients with established disease. No trend in favour of sulphasalazine over the control group was observed. The difficulties of such a trial due to the small number of patients entered from nine hospitals, the varied nature of the disease, and the high incidence of complications, such as intraperitoneal abscess formation, are discussed.", "contents": "Sulphasalazine in asymptomatic Crohn's disease. A multicentre trial. During a six year period 43 patients with Crohns disease were included in a double-blind controlled trial of sulphasalazine given for one year as a possible treatment for reducing the relapse rate after resection or in asymptomatic patients with established disease. No trend in favour of sulphasalazine over the control group was observed. The difficulties of such a trial due to the small number of patients entered from nine hospitals, the varied nature of the disease, and the high incidence of complications, such as intraperitoneal abscess formation, are discussed."}
{"id": "PMID:14058", "title": "Differences in the reactivities of human urokinase and the porcine tissue plasminogen activator.", "content": "It has previously been shown, that large differences exist between the effects of 6-aminohexanoic acid or alpha1-antitrypsin on fibrinolysis caused by a porcine tissue plasminogen activator or by human urokinase, while insignificant differences exist between the effects of a number of natural protease inhibitors on fibrinolysis caused by the two types of plasminogen activator. The present study shows that changes in substrate composition (pH, ionic strength fibrinogen concentration, plasminogen concentration) may influence to different degrees the fibrinolytic activities of human urokinase and the porcine tissue plasminogen activator. It is suggested, that this finding is partly related to marked differences in affinity for fibrin of the two activators.", "contents": "Differences in the reactivities of human urokinase and the porcine tissue plasminogen activator. It has previously been shown, that large differences exist between the effects of 6-aminohexanoic acid or alpha1-antitrypsin on fibrinolysis caused by a porcine tissue plasminogen activator or by human urokinase, while insignificant differences exist between the effects of a number of natural protease inhibitors on fibrinolysis caused by the two types of plasminogen activator. The present study shows that changes in substrate composition (pH, ionic strength fibrinogen concentration, plasminogen concentration) may influence to different degrees the fibrinolytic activities of human urokinase and the porcine tissue plasminogen activator. It is suggested, that this finding is partly related to marked differences in affinity for fibrin of the two activators."}
{"id": "PMID:14060", "title": "[Synthesis of norepinephrine from 3,4-dihydroxyphenylserine by L-aromatic amino acid decarboxylase of the rat brain and kidneys].", "content": "The enzymic decarboxylation of stereoisomers of DOPS was examined using rat brain and kidney decarboxylase. Optimal assay conditions for racemic threo- and racemic erythro-DOPS decarboxylation were determined by the experiments concerning 1) time course, linear for 20 min, 2) optimal pH, pH 8.2, 3) optimal temperature, 37 degrees C except racemic L-threo-DOPS decarboxylation by kidney enzyme and 4) protein concentration, 1 to 5 mg in incubation medium. Under the optimal assay condition, Km of brain enzyme for L-threo-DOPS was 1.43 X 10(-3)M and Vmax, 2.22 nmoles NE/mg/15min, and Km for racemic erythro-DOPS was 10(-3)M  and Vmas, 4.3 nmoles NE/mg/15min. Km of kidney enzyme for L-threo-DOPS was 1.37 X 10(-3)M and Vmax 21 nmoles NE/mg/15min, and Km for racemic erythro-DOPS was 8.7 X 10(-4)M and Vmax, 16.7 nmoles NE/mg/15min. On the other hand, D-threo and D-erythro-DOPS were scarcely decarboxylated. Decarboxylation of L-threo-DOPS in kidney enzyme was markedly inhibited by D-threo-DOPS. Kinetic analysis revealed that the type of inhibition was non-competitive. In helically-cut strips of isolated rabbit aorta, the contractile response to NE (10(-8)g/ml) formed from L-threo-DOPS was 95% that of 1-NE (10(-8)g/ml) while the response to NE (10(-8)g/ml) formed from racemic erythro-DOPS was not detectable. These results suggest that L-threo-DOPS is a more effective precursor of natural 1-NE than racemic threo-DOPS.", "contents": "[Synthesis of norepinephrine from 3,4-dihydroxyphenylserine by L-aromatic amino acid decarboxylase of the rat brain and kidneys]. The enzymic decarboxylation of stereoisomers of DOPS was examined using rat brain and kidney decarboxylase. Optimal assay conditions for racemic threo- and racemic erythro-DOPS decarboxylation were determined by the experiments concerning 1) time course, linear for 20 min, 2) optimal pH, pH 8.2, 3) optimal temperature, 37 degrees C except racemic L-threo-DOPS decarboxylation by kidney enzyme and 4) protein concentration, 1 to 5 mg in incubation medium. Under the optimal assay condition, Km of brain enzyme for L-threo-DOPS was 1.43 X 10(-3)M and Vmax, 2.22 nmoles NE/mg/15min, and Km for racemic erythro-DOPS was 10(-3)M  and Vmas, 4.3 nmoles NE/mg/15min. Km of kidney enzyme for L-threo-DOPS was 1.37 X 10(-3)M and Vmax 21 nmoles NE/mg/15min, and Km for racemic erythro-DOPS was 8.7 X 10(-4)M and Vmax, 16.7 nmoles NE/mg/15min. On the other hand, D-threo and D-erythro-DOPS were scarcely decarboxylated. Decarboxylation of L-threo-DOPS in kidney enzyme was markedly inhibited by D-threo-DOPS. Kinetic analysis revealed that the type of inhibition was non-competitive. In helically-cut strips of isolated rabbit aorta, the contractile response to NE (10(-8)g/ml) formed from L-threo-DOPS was 95% that of 1-NE (10(-8)g/ml) while the response to NE (10(-8)g/ml) formed from racemic erythro-DOPS was not detectable. These results suggest that L-threo-DOPS is a more effective precursor of natural 1-NE than racemic threo-DOPS."}
{"id": "PMID:14061", "title": "The fermentative production of oxytetracycline on industrial by-products by Streptomyces rimosus 12907.", "content": "Three strains of Streptomyces rimosus were grown on four different media. The one suitable for the production of oxytetracycline by Streptomyces rimosus 12907 was modified by black strap molasses, fodder yeast (40% total protein) and rice bran. The volume of the fermentation medium was sealed up in a 1200-litre fermentor aerated with sterile air obtained from a system used in the purification of air. 850 g crude oxytetracycline was obtained when the fermented medium (700 litres) was extracted with 1-butanol.", "contents": "The fermentative production of oxytetracycline on industrial by-products by Streptomyces rimosus 12907. Three strains of Streptomyces rimosus were grown on four different media. The one suitable for the production of oxytetracycline by Streptomyces rimosus 12907 was modified by black strap molasses, fodder yeast (40% total protein) and rice bran. The volume of the fermentation medium was sealed up in a 1200-litre fermentor aerated with sterile air obtained from a system used in the purification of air. 850 g crude oxytetracycline was obtained when the fermented medium (700 litres) was extracted with 1-butanol."}
{"id": "PMID:14063", "title": "[Congenital gastrointestinal diseases with manifestations in adulthood].", "content": "A genetic background is discussed in many disorders of the gastrointestinal tract with a disposition in addition to environmental factors. The pathophysiology of most hereditary diseases is unknown although the mode of inheritance is established. Biochemical analysis may show molecular defects or inborn lack of enzymes, cytogenetic studies may reveal chromosomal abnormalities. The knowledge of genetic factors in gastrointestinal disorders may contribute to the early detection of persons afflicted but not yet symptomatic, in some rare syndromes genetic counseling may become mandatory. Finally, there are many congenital malformations which may not cause symptoms for many years so that doubts may arise whether they are developmental anomalies or acquired conditions.", "contents": "[Congenital gastrointestinal diseases with manifestations in adulthood]. A genetic background is discussed in many disorders of the gastrointestinal tract with a disposition in addition to environmental factors. The pathophysiology of most hereditary diseases is unknown although the mode of inheritance is established. Biochemical analysis may show molecular defects or inborn lack of enzymes, cytogenetic studies may reveal chromosomal abnormalities. The knowledge of genetic factors in gastrointestinal disorders may contribute to the early detection of persons afflicted but not yet symptomatic, in some rare syndromes genetic counseling may become mandatory. Finally, there are many congenital malformations which may not cause symptoms for many years so that doubts may arise whether they are developmental anomalies or acquired conditions."}
{"id": "PMID:14064", "title": "[Significance of gamma-glutamyl-transpeptidase in the diagnosis of liver diseases].", "content": "The serum levels of gamma-GT are raised early in most hepatic disorders. The highest levels usually are found in cholestasis, especially due to malignancy of the liver and the pancreas and in chronic alcoholism and drug abuse. The gamma-GT is not strictly a cholestatic enzyme. The highest score of information is yielded in alcoholic liver disease.", "contents": "[Significance of gamma-glutamyl-transpeptidase in the diagnosis of liver diseases]. The serum levels of gamma-GT are raised early in most hepatic disorders. The highest levels usually are found in cholestasis, especially due to malignancy of the liver and the pancreas and in chronic alcoholism and drug abuse. The gamma-GT is not strictly a cholestatic enzyme. The highest score of information is yielded in alcoholic liver disease."}
{"id": "PMID:14065", "title": "[Therapy of peptic ulcer and chronic pancreatitis].", "content": "Medical treatment of gastric and duodenal ulcerations has recently been improved and extended by anti-aggressive and protectively acting drugs (e.g., H2-receptor antagonists and carbenoxolone sodium). However, antacids and anticholinergic treatment are still being used in modern ulcer management. The most important therapeutical measures against  chronic relapsing pancreatitis are abstinence from ethanol and surgical treatment of biliary or pancreatic duct obstructions. Symptomatic management--pancreatic enzyme substitution and analgetics, antacids, anticholinergics--is adequate in pancreatic insufficiency and during acute exacerbation, respectively.", "contents": "[Therapy of peptic ulcer and chronic pancreatitis]. Medical treatment of gastric and duodenal ulcerations has recently been improved and extended by anti-aggressive and protectively acting drugs (e.g., H2-receptor antagonists and carbenoxolone sodium). However, antacids and anticholinergic treatment are still being used in modern ulcer management. The most important therapeutical measures against  chronic relapsing pancreatitis are abstinence from ethanol and surgical treatment of biliary or pancreatic duct obstructions. Symptomatic management--pancreatic enzyme substitution and analgetics, antacids, anticholinergics--is adequate in pancreatic insufficiency and during acute exacerbation, respectively."}
{"id": "PMID:14066", "title": "[Paroxysmal alveolar hypoventilation syndrome (author's transl)].", "content": "The case of a 42-year-old female patient with central disturbance of respiration was reported which, contrary to the previously described forms of central alveolar hypoventilation, could be characterized by paroxysmal-like apnoic conditions without any feeling of suffocation. Clinically, initial cardiopulmonary complications were primary in this central disturbance of respiration. The possibility of isolated apnoic paroxysms as an expression of a true cerebro-organic nature of the attacks was described. In addition, the attempt was made to localize the morphological or functional disturbance at the basis of the observed pathological process in the bulbopontine area of the brain stem on the ventral side of the medulla in the area of the point of exit of the seventh to the twelfth cranial nerves. With anticonvulsive and analeptic treatment, a distinct improvement could be observed in the disease after the cardiopulmonary complications had subsided.", "contents": "[Paroxysmal alveolar hypoventilation syndrome (author's transl)]. The case of a 42-year-old female patient with central disturbance of respiration was reported which, contrary to the previously described forms of central alveolar hypoventilation, could be characterized by paroxysmal-like apnoic conditions without any feeling of suffocation. Clinically, initial cardiopulmonary complications were primary in this central disturbance of respiration. The possibility of isolated apnoic paroxysms as an expression of a true cerebro-organic nature of the attacks was described. In addition, the attempt was made to localize the morphological or functional disturbance at the basis of the observed pathological process in the bulbopontine area of the brain stem on the ventral side of the medulla in the area of the point of exit of the seventh to the twelfth cranial nerves. With anticonvulsive and analeptic treatment, a distinct improvement could be observed in the disease after the cardiopulmonary complications had subsided."}
{"id": "PMID:14067", "title": "[The use of beta-blocking agents in psychiatry and neurology (author's transl)].", "content": "This paper is an up-to-date review of the literature on the subject, as well as of own research. The paper discusses pharmacological and experimental data concerning the central nervous activity of beta-blocking agents. Their use in anxiolysis - in adults and children -, ethological research, their indications in the treatment of various psychoses, withdrawal syndromes of opiate, alcohol, hypnotics, tranquilizers, marihuana and amphetamine addiction, Parkinson, essential, familiar, senile and lithium induced tremors, as well as in side effects of other psychopharmacological drugs is analysed. The relevance of different studies and therapeutical indications is discussed. Finally, tha paper points to the side-effects, advantages and disadvantages of the above substances in neuro-psychiatric therapy and stresses their importance for future research.", "contents": "[The use of beta-blocking agents in psychiatry and neurology (author's transl)]. This paper is an up-to-date review of the literature on the subject, as well as of own research. The paper discusses pharmacological and experimental data concerning the central nervous activity of beta-blocking agents. Their use in anxiolysis - in adults and children -, ethological research, their indications in the treatment of various psychoses, withdrawal syndromes of opiate, alcohol, hypnotics, tranquilizers, marihuana and amphetamine addiction, Parkinson, essential, familiar, senile and lithium induced tremors, as well as in side effects of other psychopharmacological drugs is analysed. The relevance of different studies and therapeutical indications is discussed. Finally, tha paper points to the side-effects, advantages and disadvantages of the above substances in neuro-psychiatric therapy and stresses their importance for future research."}
{"id": "PMID:14068", "title": "[Purification and properties of two beta-glycosidases from Cicer arietinum L. with preferential specificity for biochanin A 7-beta-apiosylglucoside (author's transl)].", "content": "Four different beta-glycosidases have been separated from leaves of chick pea plants, Cicer arietinum L., by DEAE-cellulose chromatography. One is specific for isoflavone 7-beta-glucosides and has been described elsewhere. Two others showed very similar protein properties and identical catalytic activities. They have been further purified and both appeared as single, homogeneous protein bands after alkaline disc electrophoresis as well as isoelectric focusing. Isoelectric points are at pH 4.35 and 4,45, respectively. Both beta-glycosidases have molecular weights of 120000-140000 and have two subunits with identical molecular weights of 65 000. Both beta-glycosidases preferentially catalyze hydrolysis of diglycosides like biochanin A 7-beta-apiosyl(1 leads to 2)glucoside (Km=1.5 X 10(-4) M; V=10 mumol X min-1 X mg-1). The apiosylglucoside unit is liberated as an intact disaccharide. beta-Glucosides like biochanin A 7-beta-glucoside or 2-nitrophenyl glucoside are also efficiently hydrolyzed. These beta-glycosidases also possess transferase activity, but only when measured with isoflavone aglycones as acceptors. Transfer of the intact apiosylglucoside unit of biochanin A 7-beta-apiosylglucoside could be demonstrated. The enzymes have a pH optimum of 5.5. The beta-glycosidates are strongly inhibited by p-hydroxymercuribenzoate and Bromocondurite. Glucono-1,5-lactone, Ag and Hg2 showed only weak inhibition and Condurit B epoxide had no effect at all. A fourth beta-glycosidase activity from chick pea leaves shows no preferential activity for isoflavone 7-glycosides.", "contents": "[Purification and properties of two beta-glycosidases from Cicer arietinum L. with preferential specificity for biochanin A 7-beta-apiosylglucoside (author's transl)]. Four different beta-glycosidases have been separated from leaves of chick pea plants, Cicer arietinum L., by DEAE-cellulose chromatography. One is specific for isoflavone 7-beta-glucosides and has been described elsewhere. Two others showed very similar protein properties and identical catalytic activities. They have been further purified and both appeared as single, homogeneous protein bands after alkaline disc electrophoresis as well as isoelectric focusing. Isoelectric points are at pH 4.35 and 4,45, respectively. Both beta-glycosidases have molecular weights of 120000-140000 and have two subunits with identical molecular weights of 65 000. Both beta-glycosidases preferentially catalyze hydrolysis of diglycosides like biochanin A 7-beta-apiosyl(1 leads to 2)glucoside (Km=1.5 X 10(-4) M; V=10 mumol X min-1 X mg-1). The apiosylglucoside unit is liberated as an intact disaccharide. beta-Glucosides like biochanin A 7-beta-glucoside or 2-nitrophenyl glucoside are also efficiently hydrolyzed. These beta-glycosidases also possess transferase activity, but only when measured with isoflavone aglycones as acceptors. Transfer of the intact apiosylglucoside unit of biochanin A 7-beta-apiosylglucoside could be demonstrated. The enzymes have a pH optimum of 5.5. The beta-glycosidates are strongly inhibited by p-hydroxymercuribenzoate and Bromocondurite. Glucono-1,5-lactone, Ag and Hg2 showed only weak inhibition and Condurit B epoxide had no effect at all. A fourth beta-glycosidase activity from chick pea leaves shows no preferential activity for isoflavone 7-glycosides."}
{"id": "PMID:14069", "title": "Effects of yeast proteinase A, proteinase B and carboxypeptidase Y on yeast phosphofructokinase.", "content": "Incubation of a crude yeast extract containing phosphofructokinase with proteinase A, proteinase B or carboxypeptidase Y gave the following results: Proteinase B and carboxypeptidase Y did not change the activity of phosphofructokinase during incubation. On the other hand, incubation with proteinase A resulted in a 40-100% activation; continued incubation, however, led to an inactivation of the enzyme. Addition of allosteric effectors did not change the activation or inactivation process. The activated phosphofructokinase was not changed with respect to pH optimum and ATP inhibition. Molecular weight determination of phosphofructokinase in crude extracts in the presence of inhibitors of proteinase A indicated a molecular weight of 700000. Without inhibitors of proteinase A, the molecular weight was determined to be 600 000, while after 40-100% activation by proteinase A, a molecular weight of 500 000 was obtained. The activity profile of proteinase A in density gradients indicated that this enzyme is bound to variety of cellular proteins.", "contents": "Effects of yeast proteinase A, proteinase B and carboxypeptidase Y on yeast phosphofructokinase. Incubation of a crude yeast extract containing phosphofructokinase with proteinase A, proteinase B or carboxypeptidase Y gave the following results: Proteinase B and carboxypeptidase Y did not change the activity of phosphofructokinase during incubation. On the other hand, incubation with proteinase A resulted in a 40-100% activation; continued incubation, however, led to an inactivation of the enzyme. Addition of allosteric effectors did not change the activation or inactivation process. The activated phosphofructokinase was not changed with respect to pH optimum and ATP inhibition. Molecular weight determination of phosphofructokinase in crude extracts in the presence of inhibitors of proteinase A indicated a molecular weight of 700000. Without inhibitors of proteinase A, the molecular weight was determined to be 600 000, while after 40-100% activation by proteinase A, a molecular weight of 500 000 was obtained. The activity profile of proteinase A in density gradients indicated that this enzyme is bound to variety of cellular proteins."}
{"id": "PMID:14070", "title": "Species distribution and properties of hepatic phenylalanine (histidine):pyruvate aminotransferase.", "content": "Hepatic phenylalanine(histidine):pyruvate aminotransferase activity is much higher in the mouse and rat than in other animal species (human, guinea-pig, rabbit, pig, dog and chicken). The activity is elevated in the mouse and rat by the injection of glucagon but not in other species (guinea-pig, rabbit and chicken). The enzyme was purified from the mitochondrial fraction of mouse liver to homogeneity as judged by polyacrylamide disc gel electrophoresis in the presence of dodecylsulphate. With histidine as amino donor, the enzyme was active with pyruvate, oxaloacetate and hydroxypyruvate as amino acceptors but not with 2-oxoglutarate. Effective amino donors were histidine, phenylalanine and tyrosine with pyruvate, and methionine, serine and glutamine with phenylpyruvate. The apparent Km for histidine was about 6.9 mM with pyruvate and that for pyruvate was 21 mM with histidine. The enzyme is probably composed of two identical subunits with a molecular weight of approximately 40000. The pH optimum was near 9.0. Isoelectric focusing of the purified enzyme resulted in the detection of four forms with pI 6.0, 6.2, 6.5 and 6.7, respectively, all of which were responsive to glucagon. These four forms were nearly identical with the purified enzyme before the focusing with respect to physical and enzymic properties. A possible mechanism of this multiplicity is discussed.", "contents": "Species distribution and properties of hepatic phenylalanine (histidine):pyruvate aminotransferase. Hepatic phenylalanine(histidine):pyruvate aminotransferase activity is much higher in the mouse and rat than in other animal species (human, guinea-pig, rabbit, pig, dog and chicken). The activity is elevated in the mouse and rat by the injection of glucagon but not in other species (guinea-pig, rabbit and chicken). The enzyme was purified from the mitochondrial fraction of mouse liver to homogeneity as judged by polyacrylamide disc gel electrophoresis in the presence of dodecylsulphate. With histidine as amino donor, the enzyme was active with pyruvate, oxaloacetate and hydroxypyruvate as amino acceptors but not with 2-oxoglutarate. Effective amino donors were histidine, phenylalanine and tyrosine with pyruvate, and methionine, serine and glutamine with phenylpyruvate. The apparent Km for histidine was about 6.9 mM with pyruvate and that for pyruvate was 21 mM with histidine. The enzyme is probably composed of two identical subunits with a molecular weight of approximately 40000. The pH optimum was near 9.0. Isoelectric focusing of the purified enzyme resulted in the detection of four forms with pI 6.0, 6.2, 6.5 and 6.7, respectively, all of which were responsive to glucagon. These four forms were nearly identical with the purified enzyme before the focusing with respect to physical and enzymic properties. A possible mechanism of this multiplicity is discussed."}
{"id": "PMID:14071", "title": "Catecholamines, adrenal hormones, and stress.", "content": "From its beginnings about a century ago, research into the mechanisms underlying the stress response has led by many avenues to the adrenal medulla and its chromaffin cells. The latter possess cholinergic synapses that, when activated by a wide variety of stimuli, trigger discharge of catecholamines directly into the blood. Control of the response is mediated by a final common pathway arising in the hypothalamus and/or midbrain.", "contents": "Catecholamines, adrenal hormones, and stress. From its beginnings about a century ago, research into the mechanisms underlying the stress response has led by many avenues to the adrenal medulla and its chromaffin cells. The latter possess cholinergic synapses that, when activated by a wide variety of stimuli, trigger discharge of catecholamines directly into the blood. Control of the response is mediated by a final common pathway arising in the hypothalamus and/or midbrain."}
{"id": "PMID:14072", "title": "Atmospheric stability in cell culture vessels.", "content": "We have investigated that atmospheric stability in polystyrene and glass cell culture vessels by measuring the dissolved O2 and CO2 in the media of both seeded and unseeded culture vessels incubated at 37 degrees C. There was no diffusion of either O2 or CO2 through glass vessels. At low partial pressures of oxygen (PO2), oxygen diffused into the polystyrene flasks at a rate of 1 to 2 mmHg per 24 hr, and at high PO2, oxygen diffused slowly out of polystyrene flasks. CO2 diffused out of polystyrene flasks with a half-time of 260 hr resulting in a considerable elevation in pH. In seeded polystyrene flasks with the PO2 less than or equal to room air, cellular oxygen consumption was masked by the inward diffusion of oxygen. In addition, the fall in pH due to metabolic CO2 and organic acid production during cell growth in polystyrene flasks was buffered by the diffusion of CO2 out of the vessels.", "contents": "Atmospheric stability in cell culture vessels. We have investigated that atmospheric stability in polystyrene and glass cell culture vessels by measuring the dissolved O2 and CO2 in the media of both seeded and unseeded culture vessels incubated at 37 degrees C. There was no diffusion of either O2 or CO2 through glass vessels. At low partial pressures of oxygen (PO2), oxygen diffused into the polystyrene flasks at a rate of 1 to 2 mmHg per 24 hr, and at high PO2, oxygen diffused slowly out of polystyrene flasks. CO2 diffused out of polystyrene flasks with a half-time of 260 hr resulting in a considerable elevation in pH. In seeded polystyrene flasks with the PO2 less than or equal to room air, cellular oxygen consumption was masked by the inward diffusion of oxygen. In addition, the fall in pH due to metabolic CO2 and organic acid production during cell growth in polystyrene flasks was buffered by the diffusion of CO2 out of the vessels."}
{"id": "PMID:14073", "title": "Culture of fetal mouse liver in plastic chambers: a new technique for organ culture.", "content": "A new technique for organ culture which uses plastic culture chambers and the advantages of the cellophane-sheet technique is described with the results of a study of cultivations of fetal mouse liver. Two chambers, each containing cells, were placed in gas permeable roller tubes and rotated at 0.1 rpm in a CO2-air gassed incubator. The fetal mouse liver cells developed electron microscopic features similar to those of the in vivo adult liver by 9 days of cultivation. The albumin content and tyrosine aminotransferase (TAT) activity were detected in the cultivated liver. TAT activity was further induced by prednisolone. These results indicate that potential of this culture method for the study of physiological and pathological processes.", "contents": "Culture of fetal mouse liver in plastic chambers: a new technique for organ culture. A new technique for organ culture which uses plastic culture chambers and the advantages of the cellophane-sheet technique is described with the results of a study of cultivations of fetal mouse liver. Two chambers, each containing cells, were placed in gas permeable roller tubes and rotated at 0.1 rpm in a CO2-air gassed incubator. The fetal mouse liver cells developed electron microscopic features similar to those of the in vivo adult liver by 9 days of cultivation. The albumin content and tyrosine aminotransferase (TAT) activity were detected in the cultivated liver. TAT activity was further induced by prednisolone. These results indicate that potential of this culture method for the study of physiological and pathological processes."}
{"id": "PMID:14076", "title": "The antihypertensive effect of lexotan (bromazepam)- a new benzodiazepine derivative.", "content": "Clinical observations led to the assumption that there is an antihypertensive effect of bromazepam in patients suffering from mild benign hypertension. Because of this observation we studied the antihypertensive effect of bromazepam by means of a standardized simple submaximal ergometric load performed weekly over a 4-week period of observation. A control group of 68 hypertensive patients without any drug therapy but under active physical training combined with physiotherapy and medicinal baths showed only a slight decrease in systolic and diastolic blood pressure at rest (about 4%). Furthermore, the pulse frequency did not change. In contrast, there was a distinct and significant decrease in blood pressure at rest and during exercise after a 3-week period of additional treatment with bromazepam, especially in hypertensive patients. One group of 68 hypertensive patients receiving 9 mg bromazepam daily showed a mean reduction in blood pressure by 14.4% systolic and 12.7% diastolic at rest, and during exercise by 7.5% systolic and 6.8% diastolic. The heart remained practically unchanged. A somewhat slighter decrease of the blood pressure values was seen in an additional group of 31 hypertensive patients receiving 6 mg bromazepam per day and in a group of 30 normotensive patients receiving 9 mg bromazepam daily. The calculated indices such as the product of heart rate and mean systolic pressure and the tension time index in the groups receiving bromazepam pointed to a better economic work performance under reduced myocardial pressure effort and reduced oxygen demand on the myocardium. The possible action of bromazepam in reducing blood pressure will be discussed.", "contents": "The antihypertensive effect of lexotan (bromazepam)- a new benzodiazepine derivative. Clinical observations led to the assumption that there is an antihypertensive effect of bromazepam in patients suffering from mild benign hypertension. Because of this observation we studied the antihypertensive effect of bromazepam by means of a standardized simple submaximal ergometric load performed weekly over a 4-week period of observation. A control group of 68 hypertensive patients without any drug therapy but under active physical training combined with physiotherapy and medicinal baths showed only a slight decrease in systolic and diastolic blood pressure at rest (about 4%). Furthermore, the pulse frequency did not change. In contrast, there was a distinct and significant decrease in blood pressure at rest and during exercise after a 3-week period of additional treatment with bromazepam, especially in hypertensive patients. One group of 68 hypertensive patients receiving 9 mg bromazepam daily showed a mean reduction in blood pressure by 14.4% systolic and 12.7% diastolic at rest, and during exercise by 7.5% systolic and 6.8% diastolic. The heart remained practically unchanged. A somewhat slighter decrease of the blood pressure values was seen in an additional group of 31 hypertensive patients receiving 6 mg bromazepam per day and in a group of 30 normotensive patients receiving 9 mg bromazepam daily. The calculated indices such as the product of heart rate and mean systolic pressure and the tension time index in the groups receiving bromazepam pointed to a better economic work performance under reduced myocardial pressure effort and reduced oxygen demand on the myocardium. The possible action of bromazepam in reducing blood pressure will be discussed."}
{"id": "PMID:14078", "title": "Studies on groundnut proteins. VI. Isolation, characterisation and hydrogen ion titration of conarachin II.", "content": "A method is described for isolating conarachin II in a homogeneous form by the techniques of DEAE-cellulose chromatography, polyacrylamide gel electrophoresis and sedimentation velocity. The protein contains 0.72% carbohydrate and no phosphate. Hydrogen ion titration curve indicated that the sidechain carboxyl, imidazol and epsilon-amino groups titrated with normal pK Int values and their number agreed with the analytical values obtained from amino acid analysis. However, tyrosine phenolic groups had abnormal pK Int of 10.5.", "contents": "Studies on groundnut proteins. VI. Isolation, characterisation and hydrogen ion titration of conarachin II. A method is described for isolating conarachin II in a homogeneous form by the techniques of DEAE-cellulose chromatography, polyacrylamide gel electrophoresis and sedimentation velocity. The protein contains 0.72% carbohydrate and no phosphate. Hydrogen ion titration curve indicated that the sidechain carboxyl, imidazol and epsilon-amino groups titrated with normal pK Int values and their number agreed with the analytical values obtained from amino acid analysis. However, tyrosine phenolic groups had abnormal pK Int of 10.5."}
{"id": "PMID:14079", "title": "Reaction of bovine and equine growth hormones with tetranitromethane.", "content": "Bovine and equine growth hormones were chemically modified with tetranitromethane, at pH 7.4 during 5 h and at pH 8.0 in the presence of 8 M urea during 1 h. a) Both hormones have very similar but not identical reactivities. b) The nitration of the reactive tyrosines and tryptophan residues at pH 7.4 produces no detectable changes in their immunological or somatotrophic activities. C) The nitration of all tyrosine residues in both hormones gives rise to a complete loss of somatographic activity with no alteration of the immunological activity.", "contents": "Reaction of bovine and equine growth hormones with tetranitromethane. Bovine and equine growth hormones were chemically modified with tetranitromethane, at pH 7.4 during 5 h and at pH 8.0 in the presence of 8 M urea during 1 h. a) Both hormones have very similar but not identical reactivities. b) The nitration of the reactive tyrosines and tryptophan residues at pH 7.4 produces no detectable changes in their immunological or somatotrophic activities. C) The nitration of all tyrosine residues in both hormones gives rise to a complete loss of somatographic activity with no alteration of the immunological activity."}
{"id": "PMID:14080", "title": "The secondary structure of histone IV and its stability.", "content": "The secondary structure within histone IV and its fragments obtained by cyanogen bromide (CNBr) and cleavage at Met 84 has been examined by circular dichroism and spectophotometric pH titration measurements. These studies have confirmed the existence of stable secondary structure within the C-terminal fragment of histone IV (C-peptide which can be perturbed only by 6M urea at pH greater than 8 or 8 M guanidine-HCL. In contrast, the N-terminal fragment (N-peptide) appears to lack significant secondary structure at low ionic strengths but acquires approximately 15% betasheet conformation and 5% alpha-helix upon aggregation at ionic strengths larger than or equal to 0.4. The rates of nitration of the N- and C-peptides by tetranitromethane (TNM) have also been measured as a function of ionic strengths. Under comparable conditions, the rate constant for nitration of the N-peptide was found to be about six times greater than that for the C-peptide, further evidence in support of the presence of stable secondary structure within the C-terminal region of histone IV. After binding these histone IV fragments to DNA, however, the nitration reaction rate constants for the N- and C-peptide in the bound form are found to be 2% and 27% of the corresponding free peptides. Reconstituted nucleohistone IV is about 10% as reactive to TNM as histone IV at comparable ionic strength.", "contents": "The secondary structure of histone IV and its stability. The secondary structure within histone IV and its fragments obtained by cyanogen bromide (CNBr) and cleavage at Met 84 has been examined by circular dichroism and spectophotometric pH titration measurements. These studies have confirmed the existence of stable secondary structure within the C-terminal fragment of histone IV (C-peptide which can be perturbed only by 6M urea at pH greater than 8 or 8 M guanidine-HCL. In contrast, the N-terminal fragment (N-peptide) appears to lack significant secondary structure at low ionic strengths but acquires approximately 15% betasheet conformation and 5% alpha-helix upon aggregation at ionic strengths larger than or equal to 0.4. The rates of nitration of the N- and C-peptides by tetranitromethane (TNM) have also been measured as a function of ionic strengths. Under comparable conditions, the rate constant for nitration of the N-peptide was found to be about six times greater than that for the C-peptide, further evidence in support of the presence of stable secondary structure within the C-terminal region of histone IV. After binding these histone IV fragments to DNA, however, the nitration reaction rate constants for the N- and C-peptide in the bound form are found to be 2% and 27% of the corresponding free peptides. Reconstituted nucleohistone IV is about 10% as reactive to TNM as histone IV at comparable ionic strength."}
{"id": "PMID:14081", "title": "Effect of clamping of the renal vein in dogs on certain biochemical and histopathological changes.", "content": "Experimental investigations were carried out on dogs in which the renal vein was clamped for a period of 15 min, 30, and 60 min consecutively. It has been found that clamping of the renal vein for 15 min results in tissue anoxia and degeneration of the epithelium of the renal tubules. Clamping for 60 min causes cellular acidosis and necrosis of the tubules. It can therefore be said that clamping of the renal vein for even a short time is highly dangerous.", "contents": "Effect of clamping of the renal vein in dogs on certain biochemical and histopathological changes. Experimental investigations were carried out on dogs in which the renal vein was clamped for a period of 15 min, 30, and 60 min consecutively. It has been found that clamping of the renal vein for 15 min results in tissue anoxia and degeneration of the epithelium of the renal tubules. Clamping for 60 min causes cellular acidosis and necrosis of the tubules. It can therefore be said that clamping of the renal vein for even a short time is highly dangerous."}
{"id": "PMID:14082", "title": "Gastric secretion.", "content": "This review has attempted to cover some of the findings that have been made in the mechanism of gastric secretion in recent years. It is hard to offer any firm conclusions, whether at the level of stimulus, metabolism, or the terminal process of secretion. However, some generalizations may be possible. At least amphibian gastric secretion is stimulated by cAMP as a second messenger, with histamine presumably acting as the primary messenger. The resultant metabolic change is due largely to a direct stimulation of catabolism, which in dog appears to be the metabolism of hexose, through the glycolytic process, the hexose monophosphate shunt, and the Krebs' cycle with cytoplasmic reduction and mitochondrial oxidation of pyridine nucleotides. No evidence could be obtained for changes in high energy phosphate or for lipolysis. One would expect gastric mucosal membranes during secretion to contain an anion-restricted electrogenic H+ pump, but they in fact contain an ATPase stimulated by monovalent cations and are insensitive to ouabain. In addition, hog or dog gastric membranes have the vectorial properties of H+ absorption, Rb+ extrusion, and ANS fluorescence enhancement with the addition of ATP, as well as protein phosphorylation by 32P dependent on a K+ gradient.", "contents": "Gastric secretion. This review has attempted to cover some of the findings that have been made in the mechanism of gastric secretion in recent years. It is hard to offer any firm conclusions, whether at the level of stimulus, metabolism, or the terminal process of secretion. However, some generalizations may be possible. At least amphibian gastric secretion is stimulated by cAMP as a second messenger, with histamine presumably acting as the primary messenger. The resultant metabolic change is due largely to a direct stimulation of catabolism, which in dog appears to be the metabolism of hexose, through the glycolytic process, the hexose monophosphate shunt, and the Krebs' cycle with cytoplasmic reduction and mitochondrial oxidation of pyridine nucleotides. No evidence could be obtained for changes in high energy phosphate or for lipolysis. One would expect gastric mucosal membranes during secretion to contain an anion-restricted electrogenic H+ pump, but they in fact contain an ATPase stimulated by monovalent cations and are insensitive to ouabain. In addition, hog or dog gastric membranes have the vectorial properties of H+ absorption, Rb+ extrusion, and ANS fluorescence enhancement with the addition of ATP, as well as protein phosphorylation by 32P dependent on a K+ gradient."}
{"id": "PMID:14089", "title": "Cellular immune competence in patients with malignant tumors of the gastrointestinal tract.", "content": "The local graft-vs-host reaction (GVHR) test was used to assess the cellular immune competence of lymphocytes obtained from 29 patients with malignant tumors of the gastrointestinal tract before and after removal of the tumor. Prior to removal most patients showed impairment of cellular immune competence; 10 to 14 days after surgery there was an improvement in a considerable number of patients. However, when tested four months later, the GVHR was again negative in some patients. The possible factors leading to deficiency in cellular immune competence and the value of the local GVHR test in the long-term follow-up of patients who have had malignant disease are discussed.", "contents": "Cellular immune competence in patients with malignant tumors of the gastrointestinal tract. The local graft-vs-host reaction (GVHR) test was used to assess the cellular immune competence of lymphocytes obtained from 29 patients with malignant tumors of the gastrointestinal tract before and after removal of the tumor. Prior to removal most patients showed impairment of cellular immune competence; 10 to 14 days after surgery there was an improvement in a considerable number of patients. However, when tested four months later, the GVHR was again negative in some patients. The possible factors leading to deficiency in cellular immune competence and the value of the local GVHR test in the long-term follow-up of patients who have had malignant disease are discussed."}
{"id": "PMID:14086", "title": "The impact of a physician assistant in diagnostic radiology [PA-DR] on the delivery of diagnostic radiologic clincial services.", "content": "A program to train highly selected, experienced radiologic technologists to become Physician Assistants in Diagnostic Radiology [PA-DRs] was initiated at the University of Kentucky Medical Center in 1970. The initial postgraduate year of employment in several different radiologic environments for the first twelve trainees has been evaluated. Their work activities, including examinations that otherwise would have been performed by a radiologist and the number of radiographs screened for evidence of diseases, were analyzed. Studies during their training show they perform these activities accurately. Lastly, the economic impact of PA-DRs and their acceptability to patients and other professionals were evaluated. The PA-DRs spent a majority of their time in activities for which they were trained. Calculated yearly \"earnings\" of the PA-DRs averaged +31,164. Their salaries ranged +18-25,000. Each PA-DR averaged saving 34% of the employing radiologist's time. They were well accepted by professional colleagues and patients.", "contents": "The impact of a physician assistant in diagnostic radiology [PA-DR] on the delivery of diagnostic radiologic clincial services. A program to train highly selected, experienced radiologic technologists to become Physician Assistants in Diagnostic Radiology [PA-DRs] was initiated at the University of Kentucky Medical Center in 1970. The initial postgraduate year of employment in several different radiologic environments for the first twelve trainees has been evaluated. Their work activities, including examinations that otherwise would have been performed by a radiologist and the number of radiographs screened for evidence of diseases, were analyzed. Studies during their training show they perform these activities accurately. Lastly, the economic impact of PA-DRs and their acceptability to patients and other professionals were evaluated. The PA-DRs spent a majority of their time in activities for which they were trained. Calculated yearly \"earnings\" of the PA-DRs averaged +31,164. Their salaries ranged +18-25,000. Each PA-DR averaged saving 34% of the employing radiologist's time. They were well accepted by professional colleagues and patients."}
{"id": "PMID:14091", "title": "The cytochemical demonstration of catalase and D-amino acid oxidase in the microbodies of teleost kidney cells.", "content": "The distribution of catalase and D-amino acid oxidase, marker enzymes for peroxisomes, was determined cytochemically in the kidney tubules of an euryhaline teleost, the three-spined stickleback. Catalase activity was localized with the diaminobenzidine technique. The presence of D-amino acid oxidase was determined using H2O2 generated by the enzyme, D-alanine as a substrate, and cerous ions for the formation of an electron-dense precipitate. Both enzymes appeared to be located in microbodies. The combined presence of these enzymes characterizes the microbodies as peroxisomes. Biochemically and cytochemically, no urate oxidase or glycolate-oxidizing L-alpha-hydroxy acid oxidase could be demonstrated. Stereological analysis of the epithelia lining the renal tubules showed that the fractional volume of the microbodies is 5 to 10 times higher in the cells of the second proximal tubules than in the other nephronic segments or the ureter. The fractional volume of the microbodies was similar in kidneys of freshwater and seawater fishes.", "contents": "The cytochemical demonstration of catalase and D-amino acid oxidase in the microbodies of teleost kidney cells. The distribution of catalase and D-amino acid oxidase, marker enzymes for peroxisomes, was determined cytochemically in the kidney tubules of an euryhaline teleost, the three-spined stickleback. Catalase activity was localized with the diaminobenzidine technique. The presence of D-amino acid oxidase was determined using H2O2 generated by the enzyme, D-alanine as a substrate, and cerous ions for the formation of an electron-dense precipitate. Both enzymes appeared to be located in microbodies. The combined presence of these enzymes characterizes the microbodies as peroxisomes. Biochemically and cytochemically, no urate oxidase or glycolate-oxidizing L-alpha-hydroxy acid oxidase could be demonstrated. Stereological analysis of the epithelia lining the renal tubules showed that the fractional volume of the microbodies is 5 to 10 times higher in the cells of the second proximal tubules than in the other nephronic segments or the ureter. The fractional volume of the microbodies was similar in kidneys of freshwater and seawater fishes."}
{"id": "PMID:14093", "title": "Sampling and storage of blood for pH and blood gas analysis.", "content": "Techniques used in sampling and storage of a blood sample for pH and gas measurements can have an important effect on the measured values. Observation of these techniques and principles will minimize in vitro alteration of the pH and blood gas values. To consider that a significant change has occurred in a pH or blood gas measurement from previous values, the change must exceed 0.015 for pH, 3 mm Hg for PCO2, 5 mm Hg for PO2, and 2 mEq/L for [HCO-3] or base excess/deficit. In vitro dilution of the blood sample with anticoagulant should be avoided because it will alter the measured PCO2 and base excess/deficit values. Arterial samples should be collected for meaningful pH and blood gas values. Central venous and free-flowing capillary blood can be used for screening procedures in normal patients but are subject to considerable error. A blood sample can be stored for up to 30 minutes at room temperature without significant change in acid-base values but only up to 12 minutes before significant changes occur in PO2. A blood sample can be stored for up to 3.5 hours in an ice-water bath without significant change in pH and for 6 hours without significant change in PCO2 or PO2. Variations of body temperatures from normal will cause a measurable change in pH and blood gas values when the blood is exposed to the normal water bath temperatures of the analyzer.", "contents": "Sampling and storage of blood for pH and blood gas analysis. Techniques used in sampling and storage of a blood sample for pH and gas measurements can have an important effect on the measured values. Observation of these techniques and principles will minimize in vitro alteration of the pH and blood gas values. To consider that a significant change has occurred in a pH or blood gas measurement from previous values, the change must exceed 0.015 for pH, 3 mm Hg for PCO2, 5 mm Hg for PO2, and 2 mEq/L for [HCO-3] or base excess/deficit. In vitro dilution of the blood sample with anticoagulant should be avoided because it will alter the measured PCO2 and base excess/deficit values. Arterial samples should be collected for meaningful pH and blood gas values. Central venous and free-flowing capillary blood can be used for screening procedures in normal patients but are subject to considerable error. A blood sample can be stored for up to 30 minutes at room temperature without significant change in acid-base values but only up to 12 minutes before significant changes occur in PO2. A blood sample can be stored for up to 3.5 hours in an ice-water bath without significant change in pH and for 6 hours without significant change in PCO2 or PO2. Variations of body temperatures from normal will cause a measurable change in pH and blood gas values when the blood is exposed to the normal water bath temperatures of the analyzer."}
{"id": "PMID:14094", "title": "Chemical modification of coriolin B.", "content": "Several derivatives of 5-ketocoriolin B (8, 11, 12) chemically modified at C-8 have been synthesized. These derivatives showed antitumor and antibacterial activity of the same degree as 5-ketocoriolin B (4) and diketocoriolin B (5) which were the most active members of the known coriolin group antibiotics. These derivatives were more stable than 4 and 5 in acidic or alkaline solution.", "contents": "Chemical modification of coriolin B. Several derivatives of 5-ketocoriolin B (8, 11, 12) chemically modified at C-8 have been synthesized. These derivatives showed antitumor and antibacterial activity of the same degree as 5-ketocoriolin B (4) and diketocoriolin B (5) which were the most active members of the known coriolin group antibiotics. These derivatives were more stable than 4 and 5 in acidic or alkaline solution."}
{"id": "PMID:14096", "title": "Causes of high blood O2 affinity of animals living at high altitude.", "content": "We have measured the partial pressure of O2 at 50% saturation (P50) and the concentration of various phosphate compounds in the erythrocytes of the bar-headed goose and the guanaco to establish the cause of the high blood O2 affinity in animals who normally reside at high altitude. The same data were obtained in the blood of two goose species, that live at sea level, and in human blood. At standard conditions (pH 7.4, PCO2 40 Torr, 37 degrees C), P50 was 29.7 Torr in the blood of the bar-headed goose and was about 10 Torr higher in the goose species living at sea level. Since the concentration of organic phosphates was not markedly different in the erythrocytes of either goose species we conclude that the hemoglobin of the bar-headed goose reacts more weakly with organic phosphates, which can also be inferred from studies on purified hemoglobin solutions. Likewise, the low P50 of guanaco blood in comparison with human blood can be explained by a reduced interaction of 2,3-bisphosphoglycerate of guanaco hemoglobin compared to the human pigment.", "contents": "Causes of high blood O2 affinity of animals living at high altitude. We have measured the partial pressure of O2 at 50% saturation (P50) and the concentration of various phosphate compounds in the erythrocytes of the bar-headed goose and the guanaco to establish the cause of the high blood O2 affinity in animals who normally reside at high altitude. The same data were obtained in the blood of two goose species, that live at sea level, and in human blood. At standard conditions (pH 7.4, PCO2 40 Torr, 37 degrees C), P50 was 29.7 Torr in the blood of the bar-headed goose and was about 10 Torr higher in the goose species living at sea level. Since the concentration of organic phosphates was not markedly different in the erythrocytes of either goose species we conclude that the hemoglobin of the bar-headed goose reacts more weakly with organic phosphates, which can also be inferred from studies on purified hemoglobin solutions. Likewise, the low P50 of guanaco blood in comparison with human blood can be explained by a reduced interaction of 2,3-bisphosphoglycerate of guanaco hemoglobin compared to the human pigment."}
{"id": "PMID:14097", "title": "Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia.", "content": "Three groups of dogs were anesthetized, paralyzed, and ventilated at constant rates with the spleen clamped. Two groups were isovolemically hemodiluted with warm dextran and plasma to hematocrits just above and below that at which O2 uptake (VO2) could not be maintained at preanemic levels. One of these groups was given propranolol to reduce the cardiac output response to anemia. The third group was ventilated on a low O2 gas mixture to decrease oxygen uptake. VO2 was thus limited at a high-delivery O2 pressure (PO2) in anemia and a low-delivery PO2 in hypoxic hypoxia. VO2 was reduced at a mixed venous PO2 of 45 Torr in anemia and at 17 Torr in hypoxic hypoxia. VO2, mixed venous PO2, and O2 delivery decreased precipitously at hematocrits below 10%. Once VO2 was limited by O2 availability, a single linear relationship (r = 0.91) was found for percent VO2 as a function of total O2 delivery (cardiac output X arterial O2 content) during both anemic and hypoxic hypoxia. The critical value for O2 delivery was 9.8 ml/kg-min. When O2 supply became limiting, VO2 apparently was not diffusion limited because it was more dependent on volume delivery rates than on delivery PO2.", "contents": "Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia. Three groups of dogs were anesthetized, paralyzed, and ventilated at constant rates with the spleen clamped. Two groups were isovolemically hemodiluted with warm dextran and plasma to hematocrits just above and below that at which O2 uptake (VO2) could not be maintained at preanemic levels. One of these groups was given propranolol to reduce the cardiac output response to anemia. The third group was ventilated on a low O2 gas mixture to decrease oxygen uptake. VO2 was thus limited at a high-delivery O2 pressure (PO2) in anemia and a low-delivery PO2 in hypoxic hypoxia. VO2 was reduced at a mixed venous PO2 of 45 Torr in anemia and at 17 Torr in hypoxic hypoxia. VO2, mixed venous PO2, and O2 delivery decreased precipitously at hematocrits below 10%. Once VO2 was limited by O2 availability, a single linear relationship (r = 0.91) was found for percent VO2 as a function of total O2 delivery (cardiac output X arterial O2 content) during both anemic and hypoxic hypoxia. The critical value for O2 delivery was 9.8 ml/kg-min. When O2 supply became limiting, VO2 apparently was not diffusion limited because it was more dependent on volume delivery rates than on delivery PO2."}
{"id": "PMID:14099", "title": "Can alveolar pCO2 exceed pulmonary end-capillary CO2? Yes.", "content": "In 1891 Christian Bohr observed that alveolar PCO2 could exceed arterial PCO2 when high levels of CO2 were present in the inspired air. He proposed that CO2 could be secreted by the lung. His hypothesis was dismissed as being due to experimental error; however, recently the same phenomenon was rediscovered using modern techniques. A possible explanation for the phenomenon may involve coupling between diffusion and chemical reaction of H+, HCO3-, and CO2 in the vicinity of a negatively charged capillary wall, causing the PCO2 to be higher near the wall that in the bulk phase of capillary blood.  Alveolar PCO2 is related to the PCO2 near the wall rather than the bulk phase PCO2. The Charged Membrane Hypotheses can explain the phenomenon of CO2 secretion not by a cellular mechanism, but a physical chemical disequilibrium within the capillary which is maintained by blood flow through the capillary.", "contents": "Can alveolar pCO2 exceed pulmonary end-capillary CO2? Yes. In 1891 Christian Bohr observed that alveolar PCO2 could exceed arterial PCO2 when high levels of CO2 were present in the inspired air. He proposed that CO2 could be secreted by the lung. His hypothesis was dismissed as being due to experimental error; however, recently the same phenomenon was rediscovered using modern techniques. A possible explanation for the phenomenon may involve coupling between diffusion and chemical reaction of H+, HCO3-, and CO2 in the vicinity of a negatively charged capillary wall, causing the PCO2 to be higher near the wall that in the bulk phase of capillary blood.  Alveolar PCO2 is related to the PCO2 near the wall rather than the bulk phase PCO2. The Charged Membrane Hypotheses can explain the phenomenon of CO2 secretion not by a cellular mechanism, but a physical chemical disequilibrium within the capillary which is maintained by blood flow through the capillary."}
{"id": "PMID:14100", "title": "Can alveolar pCO2 exceed pulmonary end-capillary CO2? No.", "content": "The exchanges and chemical reactions of CO2 within the blood are not complete during its transit time through the alveolar capillaries, so that theoretically alveolar PCO2 cannot exactly equal end-capillary blood PCO2. However, as a practical matter, the technical errors in determining alveolar and peripheral arterial PCO2 are so large in comparison with the difference between pulmonary arterial PCO2 and pulmonary venous PCO2, owing to the large effective solubility of CO2 in blood, that for this reason alone any difference between alveolar and end-capillary PCO2 can be neglected. The hypothetical mechanism that was originally proposed by Gurtner, Song, and Farhi for the production of an alveolar PCO2 greater than end-capillary PCO2 during rebreathing and depends on the existence of a radial gradient of H+ X HCO3- in the capillary blood near the wall appears unlikely because a) it would require a significant separation of charged ions over a large proportion of the capillary length and for a large proportion of the blood transit time and b) it would require a large radial gradient of PCO2 within the blood which on thermodynamic grounds would in turn require an unreasonable amount of energy to maintain.", "contents": "Can alveolar pCO2 exceed pulmonary end-capillary CO2? No. The exchanges and chemical reactions of CO2 within the blood are not complete during its transit time through the alveolar capillaries, so that theoretically alveolar PCO2 cannot exactly equal end-capillary blood PCO2. However, as a practical matter, the technical errors in determining alveolar and peripheral arterial PCO2 are so large in comparison with the difference between pulmonary arterial PCO2 and pulmonary venous PCO2, owing to the large effective solubility of CO2 in blood, that for this reason alone any difference between alveolar and end-capillary PCO2 can be neglected. The hypothetical mechanism that was originally proposed by Gurtner, Song, and Farhi for the production of an alveolar PCO2 greater than end-capillary PCO2 during rebreathing and depends on the existence of a radial gradient of H+ X HCO3- in the capillary blood near the wall appears unlikely because a) it would require a significant separation of charged ions over a large proportion of the capillary length and for a large proportion of the blood transit time and b) it would require a large radial gradient of PCO2 within the blood which on thermodynamic grounds would in turn require an unreasonable amount of energy to maintain."}
{"id": "PMID:14101", "title": "Pulmonary vascular response to increase in intracranial pressure: role of sympathetic mechanisms.", "content": "The pulmonary vascular response to intracranial hypertension was studied in anesthetized controlled ventilated dogs in which intracranial pressure (ICP) was elevated to 20 Torr below the mean arterial pressure for a 20-min period, and regulated at this level. Pulmonary vascular resistance (PVR) increased from control value of 2.7 +/- 0.30 to 8.3 +/- 0.51 Torr-l-1-min at the end of 20-min increase in ICP. The increase in PVR was associated with marked increase (P less than 0.001) in pulmonary arterial pressure from 14.4 +/- 1.3 to 35.4 +/- 4.0 Torr, small increase in left atrial pressure from 5.4 +/- 1.2 to 7.9 +/- 1.9 Torr, and no significant change in pulmonary blood flow. The increase in PVR occurred independently of changes in the arterial pressure. The increase in PVR induced by elevated ICP was correlated with increases in lung water, physiological shunt (Qs/Qt), alveolar dead space (VD), and with hypoxemia. Pretreatment with propranolol (1.5 mg-kg-1) attenuated the increase in PVR during elevation in ICP; the smaller increase in PVR was associated with a marked increase in left atrial pressure and a smaller increase in pulmonary perfusion pressure than in the control group. The propranolol-treated dogs also developed increases in lung water, Qs/Qt, VD, and hypoxemia. In contrast, pretreatment with phenoxybenzamine (1.5 mg-kg-1) inhibited the increases in pulmonary perfusion pressure and PVR induced by ICP elevation as well as the associated increases in lung water, Qs/Qt, VD, and hypoxemia. Therefore, a sustained elevation in ICP at a level below the mean arterial pressure in the intact dog evokes pulmonary vasoconstriction which is mediated by alpha-adrenergic mechanisms. The neurogenic pulmonary vasoconstriction results in the increases in lung water, Qs/Qt, VD, and in the hypoxemia.", "contents": "Pulmonary vascular response to increase in intracranial pressure: role of sympathetic mechanisms. The pulmonary vascular response to intracranial hypertension was studied in anesthetized controlled ventilated dogs in which intracranial pressure (ICP) was elevated to 20 Torr below the mean arterial pressure for a 20-min period, and regulated at this level. Pulmonary vascular resistance (PVR) increased from control value of 2.7 +/- 0.30 to 8.3 +/- 0.51 Torr-l-1-min at the end of 20-min increase in ICP. The increase in PVR was associated with marked increase (P less than 0.001) in pulmonary arterial pressure from 14.4 +/- 1.3 to 35.4 +/- 4.0 Torr, small increase in left atrial pressure from 5.4 +/- 1.2 to 7.9 +/- 1.9 Torr, and no significant change in pulmonary blood flow. The increase in PVR occurred independently of changes in the arterial pressure. The increase in PVR induced by elevated ICP was correlated with increases in lung water, physiological shunt (Qs/Qt), alveolar dead space (VD), and with hypoxemia. Pretreatment with propranolol (1.5 mg-kg-1) attenuated the increase in PVR during elevation in ICP; the smaller increase in PVR was associated with a marked increase in left atrial pressure and a smaller increase in pulmonary perfusion pressure than in the control group. The propranolol-treated dogs also developed increases in lung water, Qs/Qt, VD, and hypoxemia. In contrast, pretreatment with phenoxybenzamine (1.5 mg-kg-1) inhibited the increases in pulmonary perfusion pressure and PVR induced by ICP elevation as well as the associated increases in lung water, Qs/Qt, VD, and hypoxemia. Therefore, a sustained elevation in ICP at a level below the mean arterial pressure in the intact dog evokes pulmonary vasoconstriction which is mediated by alpha-adrenergic mechanisms. The neurogenic pulmonary vasoconstriction results in the increases in lung water, Qs/Qt, VD, and in the hypoxemia."}
{"id": "PMID:14102", "title": "Cardiovascular, respiratory, and metabolic adjustments to exercise in dogs.", "content": "Cardiovascular and metabolic parameters were studied in dogs anesthetized with pentobarbital sodium, and while awake resting or exercising for 30 min at either 6.4 km/h, 10% grade (32% VO2 max) or 8.0 km/h, 16% grade (50% VO2 max). The anesthetized dogs had lower cardiac outputs, stroke volumes, arterial-mixed venous oxygen differences, oxygen uptakes, rectal temperatures, and higher diastolic and mean arterial pressures than awake resting dogs. Heart rates and arterial systolic pressures were similar in the two conditions. The increased oxygen uptakes during exercise were associated with approximately equal percentage increments in cardiac outputs and oxygen extractions. Cardiac output increases during exercise were largely due to increases in heart rates. Arterial CO2 tension and CO2 contents as well as venous O2 and CO2 gas tensions and contents declined, and pH and rectal temperatures increased during exercise. The dogs became alkalotic during exercise. Elevated central body temperatures appeared to be the major factor controlling respiration.", "contents": "Cardiovascular, respiratory, and metabolic adjustments to exercise in dogs. Cardiovascular and metabolic parameters were studied in dogs anesthetized with pentobarbital sodium, and while awake resting or exercising for 30 min at either 6.4 km/h, 10% grade (32% VO2 max) or 8.0 km/h, 16% grade (50% VO2 max). The anesthetized dogs had lower cardiac outputs, stroke volumes, arterial-mixed venous oxygen differences, oxygen uptakes, rectal temperatures, and higher diastolic and mean arterial pressures than awake resting dogs. Heart rates and arterial systolic pressures were similar in the two conditions. The increased oxygen uptakes during exercise were associated with approximately equal percentage increments in cardiac outputs and oxygen extractions. Cardiac output increases during exercise were largely due to increases in heart rates. Arterial CO2 tension and CO2 contents as well as venous O2 and CO2 gas tensions and contents declined, and pH and rectal temperatures increased during exercise. The dogs became alkalotic during exercise. Elevated central body temperatures appeared to be the major factor controlling respiration."}
{"id": "PMID:14103", "title": "Effect of respiratory acidosis and activity on airway smooth muscle intracellular pH.", "content": "Previous work in our laboratory has shown that respiratory acidosis (RA) impaired mechanical function in canine tracheal smooth muscle (TSM). Since an intracellular acidosis could be brought on by the increased CO2 content of the bathing medium and alter the Km's of rate-limiting glycolytic enzymes in the pathway of energy production for contractile function, we have investigated the effects of RA on the intracellular pH (pHi) of TSM. Using the DMO method, paired unstimulated or resting TSM strips were incubated under normocapnic conditions (PO2 600 Torr, PCO2 40 Torr, pH 7.40) and RA (PO2 550 Torr, PCO2 110 Torr, pH 6.95) with 14C-labeled DMO and 3H-labeled inulin or PEG-4000. In another set of paired experiments, TSM strips were tetanized electrically every 5 min or pharmacologically throughout the incubation period (\"active\" muscle strips). The tissue and an aliquot of bathing medium were counted for 3H and 14C content and the values entered into the Wadell and Butler equation. The pHi's of \"resting\" normocapnic and acidotic strips were 7.041 +/- 0.017 (SE) and 6.752 +/- 0.012, respectively. However, the pHi's of \"active\" normocapnic and acidotic strips were 7.275 +/- 0.017 and 7.017 +/- 0.015, respectively. We conclude that respiratory acidosis lowers intracellular pH in both resting and mechanically active TSM's; however, \"active\" preparations whether exposed to normocapnia or acidosis were unexpectedly more alkaline than their \"resting\" counterparts.", "contents": "Effect of respiratory acidosis and activity on airway smooth muscle intracellular pH. Previous work in our laboratory has shown that respiratory acidosis (RA) impaired mechanical function in canine tracheal smooth muscle (TSM). Since an intracellular acidosis could be brought on by the increased CO2 content of the bathing medium and alter the Km's of rate-limiting glycolytic enzymes in the pathway of energy production for contractile function, we have investigated the effects of RA on the intracellular pH (pHi) of TSM. Using the DMO method, paired unstimulated or resting TSM strips were incubated under normocapnic conditions (PO2 600 Torr, PCO2 40 Torr, pH 7.40) and RA (PO2 550 Torr, PCO2 110 Torr, pH 6.95) with 14C-labeled DMO and 3H-labeled inulin or PEG-4000. In another set of paired experiments, TSM strips were tetanized electrically every 5 min or pharmacologically throughout the incubation period (\"active\" muscle strips). The tissue and an aliquot of bathing medium were counted for 3H and 14C content and the values entered into the Wadell and Butler equation. The pHi's of \"resting\" normocapnic and acidotic strips were 7.041 +/- 0.017 (SE) and 6.752 +/- 0.012, respectively. However, the pHi's of \"active\" normocapnic and acidotic strips were 7.275 +/- 0.017 and 7.017 +/- 0.015, respectively. We conclude that respiratory acidosis lowers intracellular pH in both resting and mechanically active TSM's; however, \"active\" preparations whether exposed to normocapnia or acidosis were unexpectedly more alkaline than their \"resting\" counterparts."}
{"id": "PMID:14104", "title": "Biochemical parameters of glutamine synthetase from Klebsiella aerogenes.", "content": "The glutamine synthetase (GS) from Klebsiella aerogenes is similar to that from Escherichia coli in several respects: (i) it is repressed by high levels of ammonia in the growth medium; (ii) its biosynthetic activity is greatly reduced by adenylylation; and (iii) adenylylation lowers the pH optimum and alters the response of the enzymes to various inhibitors in the gamma-glutamyl transferase (gammaGT) assay. There are, however, several important differences: (i) the isoactivity point for the adenylylated and non-adenylylated forms in the gammaGT assay occurs at pH 7.55 in K. aerogenes and at pH 7.15 in E. coli; (ii) the non-adenylylated form of the GS from K. aerogenes is stimulated by 60 mM MgCl2 in the gammaGT assay at pH 7.15. A biosynthetic reaction assay that correlates well with number of non-adenylylated enzyme subunits, as determined by the method of Mg2+ inhibition of the gammaGT assay, is described. Finally, we have found that it is necessary to use special methods to harvest growing cells to prevent changes in the adenylylation state of GS from occurring during harvesting.", "contents": "Biochemical parameters of glutamine synthetase from Klebsiella aerogenes. The glutamine synthetase (GS) from Klebsiella aerogenes is similar to that from Escherichia coli in several respects: (i) it is repressed by high levels of ammonia in the growth medium; (ii) its biosynthetic activity is greatly reduced by adenylylation; and (iii) adenylylation lowers the pH optimum and alters the response of the enzymes to various inhibitors in the gamma-glutamyl transferase (gammaGT) assay. There are, however, several important differences: (i) the isoactivity point for the adenylylated and non-adenylylated forms in the gammaGT assay occurs at pH 7.55 in K. aerogenes and at pH 7.15 in E. coli; (ii) the non-adenylylated form of the GS from K. aerogenes is stimulated by 60 mM MgCl2 in the gammaGT assay at pH 7.15. A biosynthetic reaction assay that correlates well with number of non-adenylylated enzyme subunits, as determined by the method of Mg2+ inhibition of the gammaGT assay, is described. Finally, we have found that it is necessary to use special methods to harvest growing cells to prevent changes in the adenylylation state of GS from occurring during harvesting."}
{"id": "PMID:14105", "title": "Isolation and properties of a thermostable restriction endonuclease (ENDO R-Bst1503).", "content": "A restriction endonuclease was isolated from Bacillus stearothermophilus1503-4R (Bst1503) and purified to homogeneity. The enzyme required Mg2+ ion as a cofactor. Bst1503 exhibited maximal activity between pH 7.5 and 8.0, between 60 and 65 degrees C, and with about 0.2 mM Mg2+. Bst1503 was not inactivated after exposure at 55 or 65 degrees C for up to 10 h. After 2 h of incubation at 70 degrees C, Bst1503 was inactivated by 65%. Bst1503 was rapidly inactivated at 75 degrees C. A single protein-staining band having a molecular weight of 46,000 was observed when Bst1503 was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was found to exist in two active forms, the predominating form with an S value of 8.3 (180,000) and the second form with an S value of 5.4 (96,000). No conversion between the 8.3S and 5.4S forms was observed after storage. Bst1503 recognized six sites in TP-1C deoxyribonucleic acid (DNA), one site in pSC101 and simian virus 40 DNAs, and three sites in lambdavir DNA. Bst1503 and BamHI were determined to be isoschizomers. The effect of temperatures on the activity and stability of BamHI was determined.", "contents": "Isolation and properties of a thermostable restriction endonuclease (ENDO R-Bst1503). A restriction endonuclease was isolated from Bacillus stearothermophilus1503-4R (Bst1503) and purified to homogeneity. The enzyme required Mg2+ ion as a cofactor. Bst1503 exhibited maximal activity between pH 7.5 and 8.0, between 60 and 65 degrees C, and with about 0.2 mM Mg2+. Bst1503 was not inactivated after exposure at 55 or 65 degrees C for up to 10 h. After 2 h of incubation at 70 degrees C, Bst1503 was inactivated by 65%. Bst1503 was rapidly inactivated at 75 degrees C. A single protein-staining band having a molecular weight of 46,000 was observed when Bst1503 was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was found to exist in two active forms, the predominating form with an S value of 8.3 (180,000) and the second form with an S value of 5.4 (96,000). No conversion between the 8.3S and 5.4S forms was observed after storage. Bst1503 recognized six sites in TP-1C deoxyribonucleic acid (DNA), one site in pSC101 and simian virus 40 DNAs, and three sites in lambdavir DNA. Bst1503 and BamHI were determined to be isoschizomers. The effect of temperatures on the activity and stability of BamHI was determined."}
{"id": "PMID:14106", "title": "Repression of the tyrosine, lysine, and methionine biosynthetic pathways in a hisT mutant of Salmonella typhimurium.", "content": "A comparison was made of the repressibility of certain enzymes in the tyrosine, methionine, and lysine biosynthetic pathways in wild-type Salmonella typhimurium and a hisT mutant. The results show that (i) tyrosine represses the synthesis of the tyrosine-sensitive 3-deoxy-D-arabino-heptulsonic acid 7-phosphate synthetase and the tyrosine aminotransferase to the same extent in a hisT mutant as in wild type and (ii) there is no detectable alteration in the extent to which methionine represses O-succinylhomoserine synthetase or in the extent to which lysine represses the lysine-sensitive beta-aspartokinase as a result of the hisT mutation.", "contents": "Repression of the tyrosine, lysine, and methionine biosynthetic pathways in a hisT mutant of Salmonella typhimurium. A comparison was made of the repressibility of certain enzymes in the tyrosine, methionine, and lysine biosynthetic pathways in wild-type Salmonella typhimurium and a hisT mutant. The results show that (i) tyrosine represses the synthesis of the tyrosine-sensitive 3-deoxy-D-arabino-heptulsonic acid 7-phosphate synthetase and the tyrosine aminotransferase to the same extent in a hisT mutant as in wild type and (ii) there is no detectable alteration in the extent to which methionine represses O-succinylhomoserine synthetase or in the extent to which lysine represses the lysine-sensitive beta-aspartokinase as a result of the hisT mutation."}
{"id": "PMID:14107", "title": "Killer toxin for sake yeast: properties and effects of adenosine 5'-diphosphate and calcium ion on killing action.", "content": "The killer character of strain isolated from the main mash of sake brewing which produces a killer substance for sake yeast was transmitted to hybrids of the strain and a standard strain of Saccharomyces cerevisiae through a cytoplasmic determinant. The character was eliminated at 41 degrees C by incubation followed by growth at 30 degrees C. The killer strain produced the killer toxin in a growth-associated manner. A preparation of crude killer toxin extract showed first-order inactivation and a linear Arrhenius plot between 25 and 40 degrees C, with an activation of energy of 55.0 kcal/mol. Addition of 1% of synthetic polymer protected the toxin from inactivation by agitation but not by heat. Enhancement of the killer action toward sensitive yeast cells by only the nucleotide adenosine 5'-diphosphate (ADP) was observed after plating on agar medium as well as after incubation in liquid medium. The addition of CaCl2 reversed the enhancing effect of ADP on killing activity. This action of CaCl2 was inhibited by cycloheximide, suggesting that protein synthesis is required for recovery of toxin-induced cells in the presence of CaCl2. Further, CaCl2 overcame the decrease in the intracellular level of adenosine 5'-triphosphate (ATP) enhanced by ADP in killer-treated cells and also inhibited leakage of ATP from the cells with immediate response. The mode of killing action is discussed in terms of a transient state of the cells and the action of ADP and CaCl2.", "contents": "Killer toxin for sake yeast: properties and effects of adenosine 5'-diphosphate and calcium ion on killing action. The killer character of strain isolated from the main mash of sake brewing which produces a killer substance for sake yeast was transmitted to hybrids of the strain and a standard strain of Saccharomyces cerevisiae through a cytoplasmic determinant. The character was eliminated at 41 degrees C by incubation followed by growth at 30 degrees C. The killer strain produced the killer toxin in a growth-associated manner. A preparation of crude killer toxin extract showed first-order inactivation and a linear Arrhenius plot between 25 and 40 degrees C, with an activation of energy of 55.0 kcal/mol. Addition of 1% of synthetic polymer protected the toxin from inactivation by agitation but not by heat. Enhancement of the killer action toward sensitive yeast cells by only the nucleotide adenosine 5'-diphosphate (ADP) was observed after plating on agar medium as well as after incubation in liquid medium. The addition of CaCl2 reversed the enhancing effect of ADP on killing activity. This action of CaCl2 was inhibited by cycloheximide, suggesting that protein synthesis is required for recovery of toxin-induced cells in the presence of CaCl2. Further, CaCl2 overcame the decrease in the intracellular level of adenosine 5'-triphosphate (ATP) enhanced by ADP in killer-treated cells and also inhibited leakage of ATP from the cells with immediate response. The mode of killing action is discussed in terms of a transient state of the cells and the action of ADP and CaCl2."}
{"id": "PMID:14108", "title": "Membrane-bound thioesterase activity in mycoplasmas.", "content": "Thioesterase activity was found in all mycoplasmas tested. Activity was highest in Acholeplasma species, whereas most of the sterol-requiring Mycoplasma species showed little activity. The thioesterase activity of Acholoplasma laidlawii is confined to the cell membrane. The enzyme could not be released from the membrane by either low- or high-ionic-strength solutions, with or without ethylenediaminetetraacetic acid, nor solubilized by detergents. The enzyme has a general specificity for long-chain saturated and unsaturated fatty acid thioesters. The preferred substrates among the saturated fatty acyl derivatives are the myristyl and palmityl derivatives. Arrhenius plots of thioesterase activities in A. laidlawii membranes enriched with elaidic or palmitic acids showed discontinuities at 12 and 18 degrees C, respectively. The possible regulatory significance of the thioesterase activity for the fatty acid synthetase and the possibllity that the activity of the enzyme is controlled by the physical state of membrane lipids are discussed.", "contents": "Membrane-bound thioesterase activity in mycoplasmas. Thioesterase activity was found in all mycoplasmas tested. Activity was highest in Acholeplasma species, whereas most of the sterol-requiring Mycoplasma species showed little activity. The thioesterase activity of Acholoplasma laidlawii is confined to the cell membrane. The enzyme could not be released from the membrane by either low- or high-ionic-strength solutions, with or without ethylenediaminetetraacetic acid, nor solubilized by detergents. The enzyme has a general specificity for long-chain saturated and unsaturated fatty acid thioesters. The preferred substrates among the saturated fatty acyl derivatives are the myristyl and palmityl derivatives. Arrhenius plots of thioesterase activities in A. laidlawii membranes enriched with elaidic or palmitic acids showed discontinuities at 12 and 18 degrees C, respectively. The possible regulatory significance of the thioesterase activity for the fatty acid synthetase and the possibllity that the activity of the enzyme is controlled by the physical state of membrane lipids are discussed."}
{"id": "PMID:14109", "title": "Characterization of autolysins from Mycobacterium smegmatis.", "content": "This study demonstrates, for the first time, the autolytic enzymes associated with mycobacterial cell walls. Based on the release of radioactivity and ninhydrin-reactive material from isolated cell walls, it was shown that maximum activity occurs during the late log phase of growth and at a buffer pH of about 8.0. Chemical analyses of autolytic digests of isolated cell walls indicated that at least three autolysins are active under the conditions used. These are N-glycolylmuramic acid-L-alanine amidase, an aminopeptidase that releases L-alanine, and an endopeptidase that solubilizes and L-alanyl-D-glutamic acid dippetide. No other endopeptidase, carboxypeptidase, or glycosidase activity was detected.", "contents": "Characterization of autolysins from Mycobacterium smegmatis. This study demonstrates, for the first time, the autolytic enzymes associated with mycobacterial cell walls. Based on the release of radioactivity and ninhydrin-reactive material from isolated cell walls, it was shown that maximum activity occurs during the late log phase of growth and at a buffer pH of about 8.0. Chemical analyses of autolytic digests of isolated cell walls indicated that at least three autolysins are active under the conditions used. These are N-glycolylmuramic acid-L-alanine amidase, an aminopeptidase that releases L-alanine, and an endopeptidase that solubilizes and L-alanyl-D-glutamic acid dippetide. No other endopeptidase, carboxypeptidase, or glycosidase activity was detected."}
{"id": "PMID:14110", "title": "Adenosine 5'-triphosphate synthesis driven by a protonmotive force in membrane vesicles of Escherichia coli.", "content": "Adenosine 5'-triphosphate (ATP) synthesis energized by an artificially imposed protonmotive force (delta p) in adenosine 5'-diphosphate-loaded membrane vesicles of Escherichia coli was investigated. The protonmotive force is composed of an artificially imposed pH gradient (delta pH) or membrane potential (deltapsi), or both. A delta pH was established by a rapid alteration of the pH of the assay medium. A delta psi was created by the establishment of diffusion potential of K+ in the presence of valinomycin. The maximal amount of ATP synthesized was 0.4 to 0.5 nmol/mg of membrane protein when energized by a delta pH and 0.2 to 0.3 nmol/mg of membrane protein when a delta psi was imposed. Simultaneous imposition of both a delta pH and delta psi resulted in the formation of greater amounts of ATP (0.8 nmol/mg of membrane protein) than with either alone. The amount of ATP synthesized was roughly proportional to the magnitude of the artificially imposed delta p. Although p-chloromercuribenzoate, 2-heptyl-4-hydroxyquinoline-N-oxide, or NaCN each inhibits oxidation of D-lactate, and thus oxidative phosphorylation, none inhibited ATP synthesis driven by an artificially imposed delta p. Membrane vesicles prepared from uncA or uncB strains, which are defective in oxidative phosphorylation, likewise were unable to catalyze ATP synthesis when energy was supplied by an artificially imposed delta p.", "contents": "Adenosine 5'-triphosphate synthesis driven by a protonmotive force in membrane vesicles of Escherichia coli. Adenosine 5'-triphosphate (ATP) synthesis energized by an artificially imposed protonmotive force (delta p) in adenosine 5'-diphosphate-loaded membrane vesicles of Escherichia coli was investigated. The protonmotive force is composed of an artificially imposed pH gradient (delta pH) or membrane potential (deltapsi), or both. A delta pH was established by a rapid alteration of the pH of the assay medium. A delta psi was created by the establishment of diffusion potential of K+ in the presence of valinomycin. The maximal amount of ATP synthesized was 0.4 to 0.5 nmol/mg of membrane protein when energized by a delta pH and 0.2 to 0.3 nmol/mg of membrane protein when a delta psi was imposed. Simultaneous imposition of both a delta pH and delta psi resulted in the formation of greater amounts of ATP (0.8 nmol/mg of membrane protein) than with either alone. The amount of ATP synthesized was roughly proportional to the magnitude of the artificially imposed delta p. Although p-chloromercuribenzoate, 2-heptyl-4-hydroxyquinoline-N-oxide, or NaCN each inhibits oxidation of D-lactate, and thus oxidative phosphorylation, none inhibited ATP synthesis driven by an artificially imposed delta p. Membrane vesicles prepared from uncA or uncB strains, which are defective in oxidative phosphorylation, likewise were unable to catalyze ATP synthesis when energy was supplied by an artificially imposed delta p."}
{"id": "PMID:14111", "title": "Induction and general properties of beta-galactosidase and beta-galactoside permease in Pseudomonas BAL-31.", "content": "The hydrolysis of o-nitrophenyl-beta-D-galactopyranoside (ONPG) by BAL-31, a marine Pseudomonas that acts as a host for bacteriophage PM2, was studied with intact cells and with cell-free extracts. A transport system for ONPG in whole cells and a beta-galactosidase activity in extracts were evident for cells grown on lactose minimal medium. It was found that the addition of isopropylthio-beta-D-galactopyranoside (IPTG) to cells growing in rich medium induced an ONPG hydrolytic activity detectable in cell extracts but cryptic in whole cells. The existence of a transport system for IPTG, which remained cryptic for ONPG, became apparent from studies of the rates of induction of beta-galactosidase as a function of cell mass at different concentrations of IPTG. The main properties of beta-galactosidase and the lactose transport system of BAL-31 were studied in terms of how they were affected by pH, temperature, or by the presence of several sugars. IPTG competitively inhibits the hydrolysis of ONPG by cell extracts. In cells pregrown on lactose, IPTG slightly inhibits the transport of ONPG. Glucose, and with less efficiency lactose, also inhibits the hydrolysis of ONPG in cell extracts. The growth of cells on lactose minimal medium was inhibited by the addition of IPTG. A mechanism for this inhibition and for the inhibition of ONPG transport by IPTG is discussed.", "contents": "Induction and general properties of beta-galactosidase and beta-galactoside permease in Pseudomonas BAL-31. The hydrolysis of o-nitrophenyl-beta-D-galactopyranoside (ONPG) by BAL-31, a marine Pseudomonas that acts as a host for bacteriophage PM2, was studied with intact cells and with cell-free extracts. A transport system for ONPG in whole cells and a beta-galactosidase activity in extracts were evident for cells grown on lactose minimal medium. It was found that the addition of isopropylthio-beta-D-galactopyranoside (IPTG) to cells growing in rich medium induced an ONPG hydrolytic activity detectable in cell extracts but cryptic in whole cells. The existence of a transport system for IPTG, which remained cryptic for ONPG, became apparent from studies of the rates of induction of beta-galactosidase as a function of cell mass at different concentrations of IPTG. The main properties of beta-galactosidase and the lactose transport system of BAL-31 were studied in terms of how they were affected by pH, temperature, or by the presence of several sugars. IPTG competitively inhibits the hydrolysis of ONPG by cell extracts. In cells pregrown on lactose, IPTG slightly inhibits the transport of ONPG. Glucose, and with less efficiency lactose, also inhibits the hydrolysis of ONPG in cell extracts. The growth of cells on lactose minimal medium was inhibited by the addition of IPTG. A mechanism for this inhibition and for the inhibition of ONPG transport by IPTG is discussed."}
{"id": "PMID:14112", "title": "Glycoprotein enzymes secreted by Aspergillus niger: purification and properties of alpha-glaactosidase.", "content": "An alpha-galactosidase (alpha-D-galactoside galactohydrolase [EC 3.2.1.22]) was purified to homogeneity from the culture filtrate of Aspergillus niger. The enzyme had an apparent molecular weight of 45,000 and was a glycoprotein. Radioactive enzyme was prepared by growing cells in [14C]fructose and this enzyme was used to prepare 14C-labeled glycopeptides. The glycopeptides emerged from Sephadex G-50 between stachyose and the glycopeptide from ovalbumin. Based on calibration of the column with various-sized dextran oligosaccharides, the glycopeptides appeared to have a molecular weight of 1,200 to 1,400. Analysis of the glycopeptide(s) indicated that it contained mannose and N-acetylglucosamine (GlcNAc) in an approximate ratio of 3 or 4 to 1. Assuming that there are two GlcNAc residues in the oligosaccharide and based on the molecular weight of the glycopeptide, the oligosaccharide probably contains eight to nine sugar residues. Alks probably attached to the protein by a GlcNAc leads to asparagine linkage. The purified alpha-galactosidase was most active on raffinose (Km = 5 x 10--4 M, Vmax = 3 mumol/min per mg of protein), but also showed good activity on p-nitrophenyl-alpha-D-galactoside ans somewhat less activity on stachyose and melibitol. The enzyme also hydrolyzed guar flour and locust bean gum, but did not attack the p-nitrophenyl glycosides of beta-galactose, alpha- or beta-glucose, or alpha- or beta-mannose.", "contents": "Glycoprotein enzymes secreted by Aspergillus niger: purification and properties of alpha-glaactosidase. An alpha-galactosidase (alpha-D-galactoside galactohydrolase [EC 3.2.1.22]) was purified to homogeneity from the culture filtrate of Aspergillus niger. The enzyme had an apparent molecular weight of 45,000 and was a glycoprotein. Radioactive enzyme was prepared by growing cells in [14C]fructose and this enzyme was used to prepare 14C-labeled glycopeptides. The glycopeptides emerged from Sephadex G-50 between stachyose and the glycopeptide from ovalbumin. Based on calibration of the column with various-sized dextran oligosaccharides, the glycopeptides appeared to have a molecular weight of 1,200 to 1,400. Analysis of the glycopeptide(s) indicated that it contained mannose and N-acetylglucosamine (GlcNAc) in an approximate ratio of 3 or 4 to 1. Assuming that there are two GlcNAc residues in the oligosaccharide and based on the molecular weight of the glycopeptide, the oligosaccharide probably contains eight to nine sugar residues. Alks probably attached to the protein by a GlcNAc leads to asparagine linkage. The purified alpha-galactosidase was most active on raffinose (Km = 5 x 10--4 M, Vmax = 3 mumol/min per mg of protein), but also showed good activity on p-nitrophenyl-alpha-D-galactoside ans somewhat less activity on stachyose and melibitol. The enzyme also hydrolyzed guar flour and locust bean gum, but did not attack the p-nitrophenyl glycosides of beta-galactose, alpha- or beta-glucose, or alpha- or beta-mannose."}
{"id": "PMID:14113", "title": "Levels of oxidized and reduced pyridine nucleotides in dormant spores and during growth, sporulation, and spore germination of Bacillus megaterium.", "content": "Dormant spores of Bacillus megaterium contained no detectable reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) despite significant levels of the oxidized forms of these nucleotides (NAD and NADP). During the first minutes of spore germination there was rapid accumulation of NADH and NADPH. However, this accumulation followed the fall in optical density that is characteristic of the initiation of spore germination. Accumulation of NADH and NADPH early in germination was not blocked by fluoride or cyanide, and it occurred even when germination was carried out in the absence of an exogenous source of reducing power. In addition to pyridine nucleotide reduction, de novo synthesis also began early in germination as the pyridine nucleotide levels increased to those found in growing cells. Midlog-phase cells grown in several different media had 20 to 35 times as much total pyridine nucleotide as did dormant spores. However, as growth and sporulation proceeded, the NADH plus NAD level fell four- to fivefold whereas the NADPH plus NADP level fell by a lesser amount. From min 10 of spore germination until midway through sporulation the value for the ratio of NADH/NAD is about 0.1 (0.03 to 0.18) while the ratio of NADPH/ANDP is about 1.4 (0.3 to 2.4). Comparison of these ratios in log-phase versus stationary phase (sporulation) growth in all three growth media tested did not reveal any common pattern of changes.", "contents": "Levels of oxidized and reduced pyridine nucleotides in dormant spores and during growth, sporulation, and spore germination of Bacillus megaterium. Dormant spores of Bacillus megaterium contained no detectable reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) despite significant levels of the oxidized forms of these nucleotides (NAD and NADP). During the first minutes of spore germination there was rapid accumulation of NADH and NADPH. However, this accumulation followed the fall in optical density that is characteristic of the initiation of spore germination. Accumulation of NADH and NADPH early in germination was not blocked by fluoride or cyanide, and it occurred even when germination was carried out in the absence of an exogenous source of reducing power. In addition to pyridine nucleotide reduction, de novo synthesis also began early in germination as the pyridine nucleotide levels increased to those found in growing cells. Midlog-phase cells grown in several different media had 20 to 35 times as much total pyridine nucleotide as did dormant spores. However, as growth and sporulation proceeded, the NADH plus NAD level fell four- to fivefold whereas the NADPH plus NADP level fell by a lesser amount. From min 10 of spore germination until midway through sporulation the value for the ratio of NADH/NAD is about 0.1 (0.03 to 0.18) while the ratio of NADPH/ANDP is about 1.4 (0.3 to 2.4). Comparison of these ratios in log-phase versus stationary phase (sporulation) growth in all three growth media tested did not reveal any common pattern of changes."}
{"id": "PMID:14114", "title": "Regulation of glnA messinger ribonucleic acid synthesis in Klebsiella aerogenes.", "content": "We examined wild-type and mutant strains of Klebsiella aerogenes for the relative amounts of ribonucleic acid (RNA) hybridizing specifically to deoxyribonucleic acid from a transducing phage carrying glnAK, the structural gene for glutamine synthetase. Our data showed a positive correlation between the intracellular level of glutamine synthetase and the level of glnA messenger RNA; we were unable to detect glnA messinger RNA in strains devoid of glutamine synthetase protein. Therefore, it is possible that transcription of glnA is not regulated simply by repression mediated through the glutamine synthetase protein; rather, autogenous control in this system may involve activation of transcription. Our experiments also suggest that the promotor of the glnA gene is located at the rha proximal end of the gene.", "contents": "Regulation of glnA messinger ribonucleic acid synthesis in Klebsiella aerogenes. We examined wild-type and mutant strains of Klebsiella aerogenes for the relative amounts of ribonucleic acid (RNA) hybridizing specifically to deoxyribonucleic acid from a transducing phage carrying glnAK, the structural gene for glutamine synthetase. Our data showed a positive correlation between the intracellular level of glutamine synthetase and the level of glnA messenger RNA; we were unable to detect glnA messinger RNA in strains devoid of glutamine synthetase protein. Therefore, it is possible that transcription of glnA is not regulated simply by repression mediated through the glutamine synthetase protein; rather, autogenous control in this system may involve activation of transcription. Our experiments also suggest that the promotor of the glnA gene is located at the rha proximal end of the gene."}
{"id": "PMID:14115", "title": "Isolation of an Escherichia coli mutant deficient in thioredoxin reductase.", "content": "A mutant of Escherichia coli defective in thioredoxin reductase has been isolated and partially characterized. This mutant has no detectable thioredoxin reductase activity in vitro and yet it exhibits no in vivo defect in reduction of ribonucleotides. Evidence is presented that indicates that, in cells permeabilized via ether treatment, ribonucleoside diphosphate reduction can utilize glutathione as an alternate reducing system.", "contents": "Isolation of an Escherichia coli mutant deficient in thioredoxin reductase. A mutant of Escherichia coli defective in thioredoxin reductase has been isolated and partially characterized. This mutant has no detectable thioredoxin reductase activity in vitro and yet it exhibits no in vivo defect in reduction of ribonucleotides. Evidence is presented that indicates that, in cells permeabilized via ether treatment, ribonucleoside diphosphate reduction can utilize glutathione as an alternate reducing system."}
{"id": "PMID:14116", "title": "Factors affecting genetic transformation of Neisseria gonorrhoeae.", "content": "Piliated gonococci were competent in genetic transformation in all stages of growth in minimal and enriched media, but nonpiliated cells were almost totally incompetent. Uptake of deoxyribonucleic acid into a deoxyribonuclease-insensitive state was observed only in competent piliated cells. Competence was not affected by washing of competent cells or treatment of competent cells with proteolytic enzymes. Expression of competence required presence of any of several different monovalent or divalent cations, as well as a utilizable source of energy. Efforts to produce genotypically or phenotypically competent derivatives of nonpiliated cells were unsuccessful. These experiments are consistent with the idea that pili may play a role in the irreversible uptake of transforming deoxyribonucleic acid by the gonococcus, but fail to provide evidence for other types of competence factors.", "contents": "Factors affecting genetic transformation of Neisseria gonorrhoeae. Piliated gonococci were competent in genetic transformation in all stages of growth in minimal and enriched media, but nonpiliated cells were almost totally incompetent. Uptake of deoxyribonucleic acid into a deoxyribonuclease-insensitive state was observed only in competent piliated cells. Competence was not affected by washing of competent cells or treatment of competent cells with proteolytic enzymes. Expression of competence required presence of any of several different monovalent or divalent cations, as well as a utilizable source of energy. Efforts to produce genotypically or phenotypically competent derivatives of nonpiliated cells were unsuccessful. These experiments are consistent with the idea that pili may play a role in the irreversible uptake of transforming deoxyribonucleic acid by the gonococcus, but fail to provide evidence for other types of competence factors."}
{"id": "PMID:14117", "title": "Glutamine synthetase of Klebsiella aerogenes: genetic and physiological properties of mutants in the adenylylation system.", "content": "Mutations resulting in defects in the adenylylation system of glutamine synthetase (GS) affect the expression of glnA, the structural gene for GS. Mutants with lesions in glnB are glutamine auxotrophs and contain repressed levels of highly adenylylated GS. Glutamine-independent revertants of the glnB3 mutant have acquired an additional mutation at the glnE site. The glnE54 mutant is incapable of adenylylating GS and produces high levels of enzyme, even when ammonia is present in the growth medium. The fact that mutations in glnB and glnE simultaneously disturb both the normal adenylylation and repression patterns of GS in Klebsiella aerogenes indicates that the adenylylation system, or adenylylation state, of GS is critical for the regulation of synthesis of GS.", "contents": "Glutamine synthetase of Klebsiella aerogenes: genetic and physiological properties of mutants in the adenylylation system. Mutations resulting in defects in the adenylylation system of glutamine synthetase (GS) affect the expression of glnA, the structural gene for GS. Mutants with lesions in glnB are glutamine auxotrophs and contain repressed levels of highly adenylylated GS. Glutamine-independent revertants of the glnB3 mutant have acquired an additional mutation at the glnE site. The glnE54 mutant is incapable of adenylylating GS and produces high levels of enzyme, even when ammonia is present in the growth medium. The fact that mutations in glnB and glnE simultaneously disturb both the normal adenylylation and repression patterns of GS in Klebsiella aerogenes indicates that the adenylylation system, or adenylylation state, of GS is critical for the regulation of synthesis of GS."}
{"id": "PMID:14118", "title": "Characterization of beta-galactosidase from a special strain of Aspergillus oryzae.", "content": "beta-Galactosidase [EC 3.2.1.23] was isolated from a partially purified preparation obtained from cultured cells of a special strain of Aspergillus oryzae, RT 102 (FERM-P1680). The enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis and was free from alpha-galactosidase, alpha- and beta-mannosidase, alpha- and beta-N-acetylhexosaminidase, and protease activities. The beta-galactosidase was capable of acting on aryl beta-galactosides, lactose, and lactosides. It also hydrolyzed beta-galactosyl linkages in urinary glycoasparagines and asialo alpha1-acid glycoprotein. The enzyme was rather stable in aqueous solution, retaining full activity at 4 degrees for at least several months. At pH 4.5, the optimum pH for the enzyme activity, and 37 degrees, full activity was maintained for several days.", "contents": "Characterization of beta-galactosidase from a special strain of Aspergillus oryzae. beta-Galactosidase [EC 3.2.1.23] was isolated from a partially purified preparation obtained from cultured cells of a special strain of Aspergillus oryzae, RT 102 (FERM-P1680). The enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis and was free from alpha-galactosidase, alpha- and beta-mannosidase, alpha- and beta-N-acetylhexosaminidase, and protease activities. The beta-galactosidase was capable of acting on aryl beta-galactosides, lactose, and lactosides. It also hydrolyzed beta-galactosyl linkages in urinary glycoasparagines and asialo alpha1-acid glycoprotein. The enzyme was rather stable in aqueous solution, retaining full activity at 4 degrees for at least several months. At pH 4.5, the optimum pH for the enzyme activity, and 37 degrees, full activity was maintained for several days."}
{"id": "PMID:14119", "title": "The structure and function of ribonuclease T1. XX. Specific inactivation of ribonuclease T1 by reaction with tosylglycolate.", "content": "1. Ribonuclease T1 [EC 3.1.4.8] was inactivated by reaction with tosylglycolate (carboxymethyl rho-toluenesulfonate). At pH 5.5 and 8.0, alkylation of the gamma-carboxyl group of glutamic acid-58 appeared to be the predominant reaction and the major cause of inactivation by tosylglycolate, as in the case of the iodoacetate reaction, although the rate of inactivation was slower than that by iodoacetate. At pH 8.0, histidine residues were also alkylated to some extent. 2. The maximal rate of inactivation was observed at around pH 5.5 and the pH dependence of the rate of inactivation suggested the implication of two groups in the reaction, with apparent pKa values of about 3-4 (possibly histidine residue(s)). 3. In the presence of substrate analogs, ribonuclease T1 was markedly protected from inactivation by tosylglycolate at pH 5.5. The extent of protection corresponded to the binding strength of the substrate analog, except for guanosine. Ribonuclease T1 was much less protected from inactivation by guanosine than by 3'-AMP or 3'-CMP, which has a lower binding strength toward ribonuclease T1. This may indicate that glutamic acid-58 is situated in the catalytic site, at which the phosphate moiety of these nucleotides directly interacts. 4. Enzyme which had been extensively inactivated with tosylglycolate at pH 5.5 scarcely reacted with iodoacetate at pH 5.5, suggesting that these reagents react at the same site, i.e. glutamic acid-58. On the other hand, enzyme which had been inactivated almost completely with tosylglycolate at pH 8.0 still reacted with iodoacetate to some extent at pH 8.0, and the modes of reaction of tosylglycolate and iodoacetate toward ribonuclease T1 appeared to be somewhat different.", "contents": "The structure and function of ribonuclease T1. XX. Specific inactivation of ribonuclease T1 by reaction with tosylglycolate. 1. Ribonuclease T1 [EC 3.1.4.8] was inactivated by reaction with tosylglycolate (carboxymethyl rho-toluenesulfonate). At pH 5.5 and 8.0, alkylation of the gamma-carboxyl group of glutamic acid-58 appeared to be the predominant reaction and the major cause of inactivation by tosylglycolate, as in the case of the iodoacetate reaction, although the rate of inactivation was slower than that by iodoacetate. At pH 8.0, histidine residues were also alkylated to some extent. 2. The maximal rate of inactivation was observed at around pH 5.5 and the pH dependence of the rate of inactivation suggested the implication of two groups in the reaction, with apparent pKa values of about 3-4 (possibly histidine residue(s)). 3. In the presence of substrate analogs, ribonuclease T1 was markedly protected from inactivation by tosylglycolate at pH 5.5. The extent of protection corresponded to the binding strength of the substrate analog, except for guanosine. Ribonuclease T1 was much less protected from inactivation by guanosine than by 3'-AMP or 3'-CMP, which has a lower binding strength toward ribonuclease T1. This may indicate that glutamic acid-58 is situated in the catalytic site, at which the phosphate moiety of these nucleotides directly interacts. 4. Enzyme which had been extensively inactivated with tosylglycolate at pH 5.5 scarcely reacted with iodoacetate at pH 5.5, suggesting that these reagents react at the same site, i.e. glutamic acid-58. On the other hand, enzyme which had been inactivated almost completely with tosylglycolate at pH 8.0 still reacted with iodoacetate to some extent at pH 8.0, and the modes of reaction of tosylglycolate and iodoacetate toward ribonuclease T1 appeared to be somewhat different."}
{"id": "PMID:14120", "title": "The structure and function of ribonuclease T1. XXI. Modification of histidine residues in ribonuclease T1 with iodoacetamide.", "content": "1. When ribonuclease T1 [EC 3.1.4.8] (0.125% solution) was treated with a 760-fold molar excess of iodoacetamide at pH 8.0 and 37 degrees, about 90% of the original activity was lost in 24 hr. The half-life of the activity was about 8 hr. The binding ability for 3'-GMP was lost simultaneously. Changes were detected only in histidine and the amino-terminal alanine residues upon amino acid analyses of the inactivated protein and its chymotryptic peptides. The inactivation occurred almost in parallel with the loss of two histidine residues in the enzyme. The pH dependences of the rate of inactivation and that of loss of histidine residues were similar and indicated the implication of a histidine residue or residues with pKa 7.5 to 8 in this reaction. 3'-GMP and guanosine showed some protective effect against loss of activity and of histidine residues. The reactivity of histidine residues was also reduced by prior modification of glutamic acid-58 with iodoacetate, of lysine-41 with maleic or cis-aconitic anhydride or 2,4,6-trinitrobenzenesulfonate or of arginine-77 with ninhydrin. 2. Analyses of the chymotryptic peptides from oxidized samples of the iodoacetamide-inactivated enzyme showed that histidine-92 and histidine-40 reacted with iodoacetamide most rapidly and at similar rates, whereas histidine-27 was least reactive. Alkylation of histidine-92 was markedly slowed down when the Glu58-carboxymethylated enzyme was treated with iodoacetamide. On the other hand, alkylation of histidine-40 was slowed down most in the presence of 3'-GMP. These results suggest that histidine-92 and histidine-40 are involved in the catalytic action, probably forming part of the catalytic site and part of the binding site, respectively, and that histidine-27 is partially buried in the enzyme molecule or interacts strongly with some other residue, thus becoming relatively unreactive.", "contents": "The structure and function of ribonuclease T1. XXI. Modification of histidine residues in ribonuclease T1 with iodoacetamide. 1. When ribonuclease T1 [EC 3.1.4.8] (0.125% solution) was treated with a 760-fold molar excess of iodoacetamide at pH 8.0 and 37 degrees, about 90% of the original activity was lost in 24 hr. The half-life of the activity was about 8 hr. The binding ability for 3'-GMP was lost simultaneously. Changes were detected only in histidine and the amino-terminal alanine residues upon amino acid analyses of the inactivated protein and its chymotryptic peptides. The inactivation occurred almost in parallel with the loss of two histidine residues in the enzyme. The pH dependences of the rate of inactivation and that of loss of histidine residues were similar and indicated the implication of a histidine residue or residues with pKa 7.5 to 8 in this reaction. 3'-GMP and guanosine showed some protective effect against loss of activity and of histidine residues. The reactivity of histidine residues was also reduced by prior modification of glutamic acid-58 with iodoacetate, of lysine-41 with maleic or cis-aconitic anhydride or 2,4,6-trinitrobenzenesulfonate or of arginine-77 with ninhydrin. 2. Analyses of the chymotryptic peptides from oxidized samples of the iodoacetamide-inactivated enzyme showed that histidine-92 and histidine-40 reacted with iodoacetamide most rapidly and at similar rates, whereas histidine-27 was least reactive. Alkylation of histidine-92 was markedly slowed down when the Glu58-carboxymethylated enzyme was treated with iodoacetamide. On the other hand, alkylation of histidine-40 was slowed down most in the presence of 3'-GMP. These results suggest that histidine-92 and histidine-40 are involved in the catalytic action, probably forming part of the catalytic site and part of the binding site, respectively, and that histidine-27 is partially buried in the enzyme molecule or interacts strongly with some other residue, thus becoming relatively unreactive."}
{"id": "PMID:14121", "title": "Dog renal kallikrein: purification and some properties.", "content": "The contents of kallikrein [EC 3.4.21.8] in the kidneys of various animals were estimated and the activity was found to be most potent in dogs. The dog renal kallikrein (DRK) was located mainly in the kidney cortex. Following the activation of a dog kidney cortex homogenate with acetone, kallikrein was purified about 2,000-fold with an overall yield of 18% by diethylaminoethyl (DEAE)-cellulose adsorption, acetone fractionation, and chromatography on Sephadex G-75 and DEAE-Sephadex A-50. The final purified preparation of dog renal kallikrein had a vasodilator activity of 65.5 KU per A280, and appeared to be homogeneous both in disc electrophoresis and ultracentrifugal analysis. Its molecular weight was estimated to be approximately 3.8 X 10(4) from the sedimentation coefficient obtained by ultracentrifugation, and by Sephadex gel filtration. However, isoelectric fractionation of the purified DRK preparation gave three isoelectric point, 3.9, 4.1, and 4.3. The DRK had an optimum pH of about 8.6 and was stable at pH 8. This enzyme was hardly inhibited by Trasylol, soybean trypsin inhibitor, ovomucoid trypsin inhibitor or potato kallikrein inhibitors. These properties were compared with those of kallikrein from other sources; DRK appeared to be similar to urinary kallikrein.", "contents": "Dog renal kallikrein: purification and some properties. The contents of kallikrein [EC 3.4.21.8] in the kidneys of various animals were estimated and the activity was found to be most potent in dogs. The dog renal kallikrein (DRK) was located mainly in the kidney cortex. Following the activation of a dog kidney cortex homogenate with acetone, kallikrein was purified about 2,000-fold with an overall yield of 18% by diethylaminoethyl (DEAE)-cellulose adsorption, acetone fractionation, and chromatography on Sephadex G-75 and DEAE-Sephadex A-50. The final purified preparation of dog renal kallikrein had a vasodilator activity of 65.5 KU per A280, and appeared to be homogeneous both in disc electrophoresis and ultracentrifugal analysis. Its molecular weight was estimated to be approximately 3.8 X 10(4) from the sedimentation coefficient obtained by ultracentrifugation, and by Sephadex gel filtration. However, isoelectric fractionation of the purified DRK preparation gave three isoelectric point, 3.9, 4.1, and 4.3. The DRK had an optimum pH of about 8.6 and was stable at pH 8. This enzyme was hardly inhibited by Trasylol, soybean trypsin inhibitor, ovomucoid trypsin inhibitor or potato kallikrein inhibitors. These properties were compared with those of kallikrein from other sources; DRK appeared to be similar to urinary kallikrein."}
{"id": "PMID:14122", "title": "The reactive site of eggplant trypsin inhibitor.", "content": "The reactive site peptide bond of the eggplant inhibitor against trypsin [EC 3.4.21.4] was identified by chemical modifications with 1,2-cyclohexanedione, 2,4,6-trinitrobenzenesulfonic acid, acetic anhydride and glyoxal, and by sequential treatments with trypsin and carboxypeptidase B [EC 3.4.12.3]. The inhibitor was significantly inactivated by chemical modifications of arginine residues, but was not affected by lysine modifications. Free arginine was released from the trypsin-modified inhibitor by carboxypeptidase B digestion, accompanied by a marked loss of inhibitory activity. A serine residue was newly exposed at the N-terminal amino acid of the inhibitor after modification with trypsin. The reactive site of the inhibitor against trypsin was concluded to be an arginylseryl bond. The inhibitor was completely inactivated by full reduction of its disulfide bonds.", "contents": "The reactive site of eggplant trypsin inhibitor. The reactive site peptide bond of the eggplant inhibitor against trypsin [EC 3.4.21.4] was identified by chemical modifications with 1,2-cyclohexanedione, 2,4,6-trinitrobenzenesulfonic acid, acetic anhydride and glyoxal, and by sequential treatments with trypsin and carboxypeptidase B [EC 3.4.12.3]. The inhibitor was significantly inactivated by chemical modifications of arginine residues, but was not affected by lysine modifications. Free arginine was released from the trypsin-modified inhibitor by carboxypeptidase B digestion, accompanied by a marked loss of inhibitory activity. A serine residue was newly exposed at the N-terminal amino acid of the inhibitor after modification with trypsin. The reactive site of the inhibitor against trypsin was concluded to be an arginylseryl bond. The inhibitor was completely inactivated by full reduction of its disulfide bonds."}
{"id": "PMID:14123", "title": "A study of the native-denatured (N in equilibrium with D) transition in lysozyme. III. Effect of alteration of net charge by acetylation.", "content": "Measurement of the enzymic activity and fluorescence properties showed that the gross conformation of acetylated lysozyme [EC 3.2.1.17] is very similar to that of the native enzyme. On the other hand, protease digestion, t-butyl hypochloride modification and thermal denaturation experiments performed on native, acetylated, and guanidinated lysozymes showed that acetylation caused a small but significant shift of the N in equilibrium with D transition to the right. Thus it can be concluded that charge balance in a protein plays an important role in maintaining its conformation. The difference between equilibrium and kinetic methods of monitoring protein denaturation was also clarified.", "contents": "A study of the native-denatured (N in equilibrium with D) transition in lysozyme. III. Effect of alteration of net charge by acetylation. Measurement of the enzymic activity and fluorescence properties showed that the gross conformation of acetylated lysozyme [EC 3.2.1.17] is very similar to that of the native enzyme. On the other hand, protease digestion, t-butyl hypochloride modification and thermal denaturation experiments performed on native, acetylated, and guanidinated lysozymes showed that acetylation caused a small but significant shift of the N in equilibrium with D transition to the right. Thus it can be concluded that charge balance in a protein plays an important role in maintaining its conformation. The difference between equilibrium and kinetic methods of monitoring protein denaturation was also clarified."}
{"id": "PMID:14124", "title": "Exchange reactions catalyzed by methioninase from Pseudomonas putida. Isolation and characterization of the exchange products.", "content": "Gel-electrophoretically homogeneous methioninase [L-methionine methanethiol-lyase (deaminating), EC 4.4.1.11] of Pseudomonas putida, which catalyzes alpha, beta- and alpha, gamma-eliminations from S-substituted amino acids, could also catalyze a variety of beta- and gamma-exchange reactions, according to the following equations: RSCH2CH(NH2)COOH+R'SH in equilibrium R'SCH2CH(NH2)COOH+RSH (beta-exchange) and RSCH2CH2CH(NH2)COOH+R'SH in equilibrium R'SCH2CH2CH(NH2)COOH+RSH (gamma-exchange), where R'SH represents an exogeneously added alkanethiol or a substituted thiol. Related amino acids not available for elimination reactions appeared to be inert as substrates for exchange. The maximum activity for the exchange reactions was observed at pH 8.5 in potassium pyrophosphate buffer. The activity increased linearly with the increase in protein concentration from zero to 3.0 mug per ml, and with incubation time up to at least 15 min at 30 degrees. Some of the exchange reaction products were purified by a combination of paper and ion exchange chromatographies, and charcoal treatment: their structures were confirmed by physicochemical methods including elemental analysis and proton magnetic resonance, infrared, and mass spectrometries.", "contents": "Exchange reactions catalyzed by methioninase from Pseudomonas putida. Isolation and characterization of the exchange products. Gel-electrophoretically homogeneous methioninase [L-methionine methanethiol-lyase (deaminating), EC 4.4.1.11] of Pseudomonas putida, which catalyzes alpha, beta- and alpha, gamma-eliminations from S-substituted amino acids, could also catalyze a variety of beta- and gamma-exchange reactions, according to the following equations: RSCH2CH(NH2)COOH+R'SH in equilibrium R'SCH2CH(NH2)COOH+RSH (beta-exchange) and RSCH2CH2CH(NH2)COOH+R'SH in equilibrium R'SCH2CH2CH(NH2)COOH+RSH (gamma-exchange), where R'SH represents an exogeneously added alkanethiol or a substituted thiol. Related amino acids not available for elimination reactions appeared to be inert as substrates for exchange. The maximum activity for the exchange reactions was observed at pH 8.5 in potassium pyrophosphate buffer. The activity increased linearly with the increase in protein concentration from zero to 3.0 mug per ml, and with incubation time up to at least 15 min at 30 degrees. Some of the exchange reaction products were purified by a combination of paper and ion exchange chromatographies, and charcoal treatment: their structures were confirmed by physicochemical methods including elemental analysis and proton magnetic resonance, infrared, and mass spectrometries."}
{"id": "PMID:14125", "title": "Determination of the intravesicular pH of fragmented sarcoplasmic reticulum with 5,5-dimethyl-2,4-oxazolidinedione.", "content": "The intravesicular pH (pHi) of fragmented sarcoplasmic reticulum (SR) of the skeletal muscle was determined from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO), a weak organic acid, between the intra- and extravesicular spaces. The pHi's thus obtained were found to be slightly lower (0.02-0.17 pH unit) than the pH's of the external medium (pHe) at pH 6.5-8.5 in the presence of 105 mM KCl and 40 mM Tris-maleate buffer. The higher the pHe, the greater the pH gradient. When pHe was changed, pHi attained equilibrium within about 20 min, the time necessary for the separation of the SR by centrifugation. When 0.25 M sucrose and 5 mM Tris-maleate buffer were used instead of 105 mM KCl and 40 mM buffer, the pH gradient increased to 0.56. It was also demonstrated by direct measurements of pHe with a glass-electrode pH meter that K+ ions added to the external medium exchanged the intravesicular H+ ions. From these results it appears that the pH gradient across the SR membrane was at the Donnan equilibrium. In this state, the Donnan potentials corresponding to pH gradients of 0.17 and 0.56 were -9.3 and -30.6 mV, respectively.", "contents": "Determination of the intravesicular pH of fragmented sarcoplasmic reticulum with 5,5-dimethyl-2,4-oxazolidinedione. The intravesicular pH (pHi) of fragmented sarcoplasmic reticulum (SR) of the skeletal muscle was determined from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO), a weak organic acid, between the intra- and extravesicular spaces. The pHi's thus obtained were found to be slightly lower (0.02-0.17 pH unit) than the pH's of the external medium (pHe) at pH 6.5-8.5 in the presence of 105 mM KCl and 40 mM Tris-maleate buffer. The higher the pHe, the greater the pH gradient. When pHe was changed, pHi attained equilibrium within about 20 min, the time necessary for the separation of the SR by centrifugation. When 0.25 M sucrose and 5 mM Tris-maleate buffer were used instead of 105 mM KCl and 40 mM buffer, the pH gradient increased to 0.56. It was also demonstrated by direct measurements of pHe with a glass-electrode pH meter that K+ ions added to the external medium exchanged the intravesicular H+ ions. From these results it appears that the pH gradient across the SR membrane was at the Donnan equilibrium. In this state, the Donnan potentials corresponding to pH gradients of 0.17 and 0.56 were -9.3 and -30.6 mV, respectively."}
{"id": "PMID:14126", "title": "Interactions of outer membrane proteins O-8 and O-9 with peptidoglycan sacculus of Escherichia coli K-12.", "content": "The outer membrane proteins O-8 and O-9 were specifically bound to the peptidoglycan sacculus in sodium dodecyl sulfate (SDS) solution. Other cellular proteins failed to interact with the peptidoglycan sacculus under the same conditions. When the outer membrane was preheated in SDS solution, the binding did not take place. Optimum binding was observed at pH 8 in the presence of 5 mM Mg2+. A high concentration of sodium chloride strongly inhibited the binding. The effects of these factors on the bindings of O-8 and O-9 required neither the bound nor the free form of Braun's lipoprotein, nor was the binding of either protein necessary for the binding of the other. Proteins O-8 and O-9 were also found in the peptidoglycan sacculus when it was prepared from cells in SDS solution at 60 degrees. A dilution experiment showed that the complex was not an artifact. The mode of interaction between these proteins and peptidoglycan in the preparation was similar to that in the reassembled O-8-O-9-peptidoglycan complex, as judged from the sensitivity to sodium chloride and temperature. The physiological importance of the complex is discussed in relation to the assembly of the outer membrane on the cell surface.", "contents": "Interactions of outer membrane proteins O-8 and O-9 with peptidoglycan sacculus of Escherichia coli K-12. The outer membrane proteins O-8 and O-9 were specifically bound to the peptidoglycan sacculus in sodium dodecyl sulfate (SDS) solution. Other cellular proteins failed to interact with the peptidoglycan sacculus under the same conditions. When the outer membrane was preheated in SDS solution, the binding did not take place. Optimum binding was observed at pH 8 in the presence of 5 mM Mg2+. A high concentration of sodium chloride strongly inhibited the binding. The effects of these factors on the bindings of O-8 and O-9 required neither the bound nor the free form of Braun's lipoprotein, nor was the binding of either protein necessary for the binding of the other. Proteins O-8 and O-9 were also found in the peptidoglycan sacculus when it was prepared from cells in SDS solution at 60 degrees. A dilution experiment showed that the complex was not an artifact. The mode of interaction between these proteins and peptidoglycan in the preparation was similar to that in the reassembled O-8-O-9-peptidoglycan complex, as judged from the sensitivity to sodium chloride and temperature. The physiological importance of the complex is discussed in relation to the assembly of the outer membrane on the cell surface."}
{"id": "PMID:14127", "title": "A novel neutral protease(s) from monkey liver.", "content": "A novel neutral protease(s), which is presumably membrane-bound, was found in monkey liver using heat-denatured casein as a substrate and was separated from other major catheptic proteases by successive procedures of gel filtration on Ultrogel AcA 22, solubilization by deoxycholate and gel filtration on Sepharose 6B. The enzyme(s) showed maximal activity at pH 8.0, and was strongly inhibited by DFP and PMSF. Many other reagents tested, including TPCK, TLCK, pCMB, iodoacetic acid, and EDTA, were without marked effect on the activity. Activation of the enzyme(s) by NaCl was not observed.", "contents": "A novel neutral protease(s) from monkey liver. A novel neutral protease(s), which is presumably membrane-bound, was found in monkey liver using heat-denatured casein as a substrate and was separated from other major catheptic proteases by successive procedures of gel filtration on Ultrogel AcA 22, solubilization by deoxycholate and gel filtration on Sepharose 6B. The enzyme(s) showed maximal activity at pH 8.0, and was strongly inhibited by DFP and PMSF. Many other reagents tested, including TPCK, TLCK, pCMB, iodoacetic acid, and EDTA, were without marked effect on the activity. Activation of the enzyme(s) by NaCl was not observed."}
{"id": "PMID:14128", "title": "Control of 3-hydroxy-3-methylglutaryl coenzyme A reductase by endogenously synthesized sterols in vitro and in vivo.", "content": "Isolated rat hepatocytes converted mevalonolactone into sterol intermediates and fatty acids 6- to 8-fold faster than mevalonate salt at concentrations less than 6 X 10(-4) M. Incubation of hepatocytes for 3 h normally results in induction of 3-hydroxy-3-methylglutaryl-CoA reductase. This increase in enzyme activity was inhibited by mevalonolactone and by mevalonate salt; at each concentration between 6 X 10(-4) M and 6 X 10(-8) M the lactone was a more effective inhibitor than the salt. The increase in enzyme activity was completely prevented by 6 X 10(-4) M lactone, and at this concentration the cells synthesized from the lactone an amount of sterol per hour which approximated that leavingthe cells in the same period. Administration of mevalonolactone to intact rats resulted in a dose-dependent inhibition of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity. At the highest dose (400 mg of (RS)-mevalonolactone/200 g of rat) enzyme activities declined 85% within 45 min and were still suppressed below normals after 28 h. Mevalonolactone treatment resulted in increases in liver cholesterol content and in the cholesterol ester concentration of liver microsomes. The results demonstrate that the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase can be controlled by the rate of endogenous sterol synthesis both in vitro and in vivo.", "contents": "Control of 3-hydroxy-3-methylglutaryl coenzyme A reductase by endogenously synthesized sterols in vitro and in vivo. Isolated rat hepatocytes converted mevalonolactone into sterol intermediates and fatty acids 6- to 8-fold faster than mevalonate salt at concentrations less than 6 X 10(-4) M. Incubation of hepatocytes for 3 h normally results in induction of 3-hydroxy-3-methylglutaryl-CoA reductase. This increase in enzyme activity was inhibited by mevalonolactone and by mevalonate salt; at each concentration between 6 X 10(-4) M and 6 X 10(-8) M the lactone was a more effective inhibitor than the salt. The increase in enzyme activity was completely prevented by 6 X 10(-4) M lactone, and at this concentration the cells synthesized from the lactone an amount of sterol per hour which approximated that leavingthe cells in the same period. Administration of mevalonolactone to intact rats resulted in a dose-dependent inhibition of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity. At the highest dose (400 mg of (RS)-mevalonolactone/200 g of rat) enzyme activities declined 85% within 45 min and were still suppressed below normals after 28 h. Mevalonolactone treatment resulted in increases in liver cholesterol content and in the cholesterol ester concentration of liver microsomes. The results demonstrate that the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase can be controlled by the rate of endogenous sterol synthesis both in vitro and in vivo."}
{"id": "PMID:14129", "title": "Binding of tritiated bovine parathyroid hormone to plasma membranes from bovine kidney cortex.", "content": "A membrane fraction enriched in parathyroid hormone (PTH)-sensitive adenylate cyclase and sodium and potassium ion-activated (Na+, K+)-ATPase was prepared from bovine kidney. Tritiated PTH binding to this membrane fraction was dependent on both hormone and membrane protein concentration. Both total and specific binding of the hormone decreased significantly after 5 to 10 min of incubation at 22 degrees. PTH binding was highly specific, being sensitive to inhibition only with active forms of unlabeled hormone (native and 1-34 PTH). Specific binding showed a pH optimum of 7.3 to 7.5. Inhibition of binding of tritiated hormone by unlabeled PTH was also highly effective at pH 6.0, but this apparently specific binding was also inhibited by adrenocorticotropic hormone, insulin, glucagon, and vasopressin. Dissociation of bound hormone was demonstrated, and an apparent dissociation constant of 4.6 X 10(-2) min-1 was obtained. Specific binding was eliminated by pretreatment of the membranes with trypsin. The concentration dependence for inhibition of binding with unlabeled PTH was identical to that for activation of adenylate cyclase in this membrane preparation, and binding was also inhibited by concentrations of calcium in the 0.5 to 2 mM range.", "contents": "Binding of tritiated bovine parathyroid hormone to plasma membranes from bovine kidney cortex. A membrane fraction enriched in parathyroid hormone (PTH)-sensitive adenylate cyclase and sodium and potassium ion-activated (Na+, K+)-ATPase was prepared from bovine kidney. Tritiated PTH binding to this membrane fraction was dependent on both hormone and membrane protein concentration. Both total and specific binding of the hormone decreased significantly after 5 to 10 min of incubation at 22 degrees. PTH binding was highly specific, being sensitive to inhibition only with active forms of unlabeled hormone (native and 1-34 PTH). Specific binding showed a pH optimum of 7.3 to 7.5. Inhibition of binding of tritiated hormone by unlabeled PTH was also highly effective at pH 6.0, but this apparently specific binding was also inhibited by adrenocorticotropic hormone, insulin, glucagon, and vasopressin. Dissociation of bound hormone was demonstrated, and an apparent dissociation constant of 4.6 X 10(-2) min-1 was obtained. Specific binding was eliminated by pretreatment of the membranes with trypsin. The concentration dependence for inhibition of binding with unlabeled PTH was identical to that for activation of adenylate cyclase in this membrane preparation, and binding was also inhibited by concentrations of calcium in the 0.5 to 2 mM range."}
{"id": "PMID:14130", "title": "Studies of binding of parathyroid hormone to a detergent-dispersed preparation from bovine kidney cortex plasma membranes.", "content": "Bovine kidney plasma membranes containing parathyroid hormone-sensitive adenylate cyclase activity were dispersed with 1% Triton X-100 and centrifuged at 150,000 X g for 2 h. Approximately 40% of the total membrane protein was extracted by this procedure. The extraction greatly reduces the fluoride-stimulated and the parathyroid hormone-sensitive adenylate cyclase activity of the membranes and yields a supernatnat which binds biologically active, tritiated parathyroid hormone. Hormone binding is stable for up to 15 h and has a linear dependence on protein concentration in the extract. Binding of the labeled hormone at concentrations of 5 to 10 nM is inhibited by preincubation with unlabeled min, and displays a dependence on temperature, time, and pH. Binding specificity is maximal at physiological pH, being inhibited by only the native hormone or its synthetic 1-34 NH2-terminal, biologically active fragment. Binding increases dramatically at pH 6.0, but is nonspecific in character. Half-maximal inhibition of the binding was achieved at 3.2 X 10(-7) M concentrations of the native hormone and 5.0 X 10(-7) M concentrations of the synthetic 1-34 NH2-terminal fragment. Calcium does not inhibit either total or specific binding. Inhibition, kinetic, and pH dependence data suggest that the extracted component(s) represent the parathyroid hormone binding protein(s) formerly identified in particulate membrane preparations.", "contents": "Studies of binding of parathyroid hormone to a detergent-dispersed preparation from bovine kidney cortex plasma membranes. Bovine kidney plasma membranes containing parathyroid hormone-sensitive adenylate cyclase activity were dispersed with 1% Triton X-100 and centrifuged at 150,000 X g for 2 h. Approximately 40% of the total membrane protein was extracted by this procedure. The extraction greatly reduces the fluoride-stimulated and the parathyroid hormone-sensitive adenylate cyclase activity of the membranes and yields a supernatnat which binds biologically active, tritiated parathyroid hormone. Hormone binding is stable for up to 15 h and has a linear dependence on protein concentration in the extract. Binding of the labeled hormone at concentrations of 5 to 10 nM is inhibited by preincubation with unlabeled min, and displays a dependence on temperature, time, and pH. Binding specificity is maximal at physiological pH, being inhibited by only the native hormone or its synthetic 1-34 NH2-terminal, biologically active fragment. Binding increases dramatically at pH 6.0, but is nonspecific in character. Half-maximal inhibition of the binding was achieved at 3.2 X 10(-7) M concentrations of the native hormone and 5.0 X 10(-7) M concentrations of the synthetic 1-34 NH2-terminal fragment. Calcium does not inhibit either total or specific binding. Inhibition, kinetic, and pH dependence data suggest that the extracted component(s) represent the parathyroid hormone binding protein(s) formerly identified in particulate membrane preparations."}
{"id": "PMID:14131", "title": "Binding of nucleotides to purified coupling factor-latent ATPase from Mycobacterium phlei.", "content": "Binding studies of various nucleotides to the purified coupling factor-latent ATPase from Mycobacterium phlei have been carried out using gel filtration, equilibrium dialysis, and ultrafiltration methods. The purified latent ATPase binds 3 mol of ADP per mol of the enzyme with an apparent dissociation constant of 68 muM. Binding of nucleotides occurred in the decreasing order: ADP, epsilon-ATP, epsilon-ADP, UDP, adenyl-5'-yl imidodiphosphate (AMP-P(NH)P), IDP, and adenosine 5'-(alpha,beta-methylene)diphosphate (AdoP(CH2)P). AMP-P(NH)P inhibits both soluble (Ki = 77 muM) and membrane-bound latent ATPase activity. However, AMP-P(NH)P does not affect oxidative phosphorylation in membrane vesicles of M. phlei. AMP-P(NH)P exhibits one binding site per molecule of the enzyme with a dissociation constant of 71 muM. After trypsin treatment of the enzyme, the binding of ADP decreases 35%, while AMP-P(NH)P binding remains unchanged. Moreover, AMP-P(NH)P binding was not displaced by ADP. Studies with sulfhydryl agents showed that, in contrast to AMP-P(NH)P, binding of at least 1 mol of ADP requires the participation of sulfhydryl groups. The results indicate that AMP-P(NH)P and ADP do not share a common binding site and that the latent ATPase enzyme has separate sites for ATP hydrolysis and ATP synthesis.", "contents": "Binding of nucleotides to purified coupling factor-latent ATPase from Mycobacterium phlei. Binding studies of various nucleotides to the purified coupling factor-latent ATPase from Mycobacterium phlei have been carried out using gel filtration, equilibrium dialysis, and ultrafiltration methods. The purified latent ATPase binds 3 mol of ADP per mol of the enzyme with an apparent dissociation constant of 68 muM. Binding of nucleotides occurred in the decreasing order: ADP, epsilon-ATP, epsilon-ADP, UDP, adenyl-5'-yl imidodiphosphate (AMP-P(NH)P), IDP, and adenosine 5'-(alpha,beta-methylene)diphosphate (AdoP(CH2)P). AMP-P(NH)P inhibits both soluble (Ki = 77 muM) and membrane-bound latent ATPase activity. However, AMP-P(NH)P does not affect oxidative phosphorylation in membrane vesicles of M. phlei. AMP-P(NH)P exhibits one binding site per molecule of the enzyme with a dissociation constant of 71 muM. After trypsin treatment of the enzyme, the binding of ADP decreases 35%, while AMP-P(NH)P binding remains unchanged. Moreover, AMP-P(NH)P binding was not displaced by ADP. Studies with sulfhydryl agents showed that, in contrast to AMP-P(NH)P, binding of at least 1 mol of ADP requires the participation of sulfhydryl groups. The results indicate that AMP-P(NH)P and ADP do not share a common binding site and that the latent ATPase enzyme has separate sites for ATP hydrolysis and ATP synthesis."}
{"id": "PMID:14132", "title": "Protein kinase activity at the inner membrane of mammalian mitochondria.", "content": "This paper reports on the discovery of a protein kinase activity associated with the inner membrane of mammalian mitochondria. The enzyme does not respond to addition of cyclic AMP or cyclic GMP and has a preference for whole histone as phosphate acceptor. Some standard assay systems for the cyclic nucleotide-dependent cytosol protein kinases would be unable to pick up this activity of the orthophosphate concentration is higher than 25 mM and the pH or the assay lower than pH 6.5. The enzyme described here has an apparent pH optimum of 8.5. Activity in liver mitochondria is not evident unless the mitochondria are disrupted by either sonication or freezing and thawing. Distribution of kinase activity in centrifugal fractions of both liver and heart mitochondrial sonicates was parallel to that of the two inner membrane marker enzymes succinic dehydrogenase and cytochrome oxidase and quite different from that of the matrix enzyme malic dehydrogenase. Experiments with preparations enriched in outer or inner membranes confirmed the contention that this enzyme is located on the inner membrane. Since disruption of the inner membrane by a freeze-thaw treatment (after the outer membrane had been disrupted by swelling in phosphate) was necessary for full expression of activity by this enzyme, the tentative conclusion was reached that substrate is accepted only from the matrix side of the inner membrane.", "contents": "Protein kinase activity at the inner membrane of mammalian mitochondria. This paper reports on the discovery of a protein kinase activity associated with the inner membrane of mammalian mitochondria. The enzyme does not respond to addition of cyclic AMP or cyclic GMP and has a preference for whole histone as phosphate acceptor. Some standard assay systems for the cyclic nucleotide-dependent cytosol protein kinases would be unable to pick up this activity of the orthophosphate concentration is higher than 25 mM and the pH or the assay lower than pH 6.5. The enzyme described here has an apparent pH optimum of 8.5. Activity in liver mitochondria is not evident unless the mitochondria are disrupted by either sonication or freezing and thawing. Distribution of kinase activity in centrifugal fractions of both liver and heart mitochondrial sonicates was parallel to that of the two inner membrane marker enzymes succinic dehydrogenase and cytochrome oxidase and quite different from that of the matrix enzyme malic dehydrogenase. Experiments with preparations enriched in outer or inner membranes confirmed the contention that this enzyme is located on the inner membrane. Since disruption of the inner membrane by a freeze-thaw treatment (after the outer membrane had been disrupted by swelling in phosphate) was necessary for full expression of activity by this enzyme, the tentative conclusion was reached that substrate is accepted only from the matrix side of the inner membrane."}
{"id": "PMID:14133", "title": "Alteration of the kinetic parameters for aminoacylation of Escherichia coli formylmethionine transfer RNA by modification of an anticodon base.", "content": "Treatment of Escherichia coli formylmethionine tRNA with 2 M sodium bisulfite, pH 7.0, in 10 mM MgCl2 at 25 degrees results in formation of uridine/bisulfite adducts at U18 in the dihydrouridine loop, U37 in the anticodon, and U48 in the variable loop. Two products, corresponding to the two diastereoisomers of 5,6-dihydrouridine-6-sulfonate, are formed at each reactive site in the tRNA. Although none of the modifications cause complete loss of methionine acceptor activity, the modified tRNA is amino-acylated at a reduced rate and has a decreased affinity for E. coli methionyl-tRNA synthetase. Aminoacylation of [35S]bisulfite-labeled tRNAfMet with a limiting amount of purified enzyme followed by separation of the acylated and unacylated molecules and structural analysis has shown that the presence of a specific diastereoisomer of the uridine/bisulfite adduct in the anticodon base U37 alters the kinetic parameters for aminoacylation of tRNAfMet.", "contents": "Alteration of the kinetic parameters for aminoacylation of Escherichia coli formylmethionine transfer RNA by modification of an anticodon base. Treatment of Escherichia coli formylmethionine tRNA with 2 M sodium bisulfite, pH 7.0, in 10 mM MgCl2 at 25 degrees results in formation of uridine/bisulfite adducts at U18 in the dihydrouridine loop, U37 in the anticodon, and U48 in the variable loop. Two products, corresponding to the two diastereoisomers of 5,6-dihydrouridine-6-sulfonate, are formed at each reactive site in the tRNA. Although none of the modifications cause complete loss of methionine acceptor activity, the modified tRNA is amino-acylated at a reduced rate and has a decreased affinity for E. coli methionyl-tRNA synthetase. Aminoacylation of [35S]bisulfite-labeled tRNAfMet with a limiting amount of purified enzyme followed by separation of the acylated and unacylated molecules and structural analysis has shown that the presence of a specific diastereoisomer of the uridine/bisulfite adduct in the anticodon base U37 alters the kinetic parameters for aminoacylation of tRNAfMet."}
{"id": "PMID:14134", "title": "beta-Glucoside hydrolase activity of normal and glucosylceramidotic cultured human skin fibroblasts.", "content": "Cultured human skin fibroblasts from normal and glucosylceramidotic subjects are found to contain one beta-glucoside hydrolase as compared with multiple enzymes in other tissues. The fibroblast enzyme has an approximate molecular weight of 150,000 under isotonic conditions, as determined by gel filtration. It occurs as a large aggregate at low ionic strength. Ceramide, 4-methylumbelliferyl, and p-nitrophenyl beta-glucosides are active as substrates. The enzyme in whole cell homogenates is membrane-bound and is solubilized by a combination of Triton X-100 and sodium taurocholate. It has a pH optimum at 4.2 and no demonstrable divalent cation requirement. The cultured fibroblast beta-glucosidase displays close similarity to one of the forms of beta-glucosidase in human spleen, specifically that form which is affected in Gaucher's disease. 4-Methylumbelliferyl beta-glucosidase activity in homozygous fibroblasts from infantile and adult forms of Gaucher's disease are reduced to 9 and 14%, respectively, of normal fibroblast activity. The residual activity in the lipidotic cells shows increased heat lability, but cannot be distinguished from that in normal cells with respect to gel exclusion properties, Michaelis constant, and pH dependence.", "contents": "beta-Glucoside hydrolase activity of normal and glucosylceramidotic cultured human skin fibroblasts. Cultured human skin fibroblasts from normal and glucosylceramidotic subjects are found to contain one beta-glucoside hydrolase as compared with multiple enzymes in other tissues. The fibroblast enzyme has an approximate molecular weight of 150,000 under isotonic conditions, as determined by gel filtration. It occurs as a large aggregate at low ionic strength. Ceramide, 4-methylumbelliferyl, and p-nitrophenyl beta-glucosides are active as substrates. The enzyme in whole cell homogenates is membrane-bound and is solubilized by a combination of Triton X-100 and sodium taurocholate. It has a pH optimum at 4.2 and no demonstrable divalent cation requirement. The cultured fibroblast beta-glucosidase displays close similarity to one of the forms of beta-glucosidase in human spleen, specifically that form which is affected in Gaucher's disease. 4-Methylumbelliferyl beta-glucosidase activity in homozygous fibroblasts from infantile and adult forms of Gaucher's disease are reduced to 9 and 14%, respectively, of normal fibroblast activity. The residual activity in the lipidotic cells shows increased heat lability, but cannot be distinguished from that in normal cells with respect to gel exclusion properties, Michaelis constant, and pH dependence."}
{"id": "PMID:14135", "title": "Transport and metabolism of vitamin B6 in lactic acid bacteria.", "content": "Streptococcus faecalis 8043 concentrates extracellular [3H]pyridoxal or [3H]pyridoxamine primarily as the corresponding 5'-phosphates. Accumulation of pyridoxamine requires an exogenous energy source and is inhibited by glycolysis inhibitors. A membrane potential is not required for transport of pyridoxamine, and an artificially generated potential does not drive uptake in this organism. Based on this and other evidence, it is concluded that S. faecalis accumulates pyridoxamine by facilitated diffusion in conjunction with trapping by pyridoxal kinase. Pyridoxamine-P is not concentrated, but equilibrates with that provided externally. Lactobacillus casei 7469 concentrates radioactivity only from pyridoxal, which appears internally as pyridoxal-P, suggesting that it too absorbs the vitamin by facilitated diffusion plus trapping. The specificity of the growth requirement of S. faecalis and L. casei for vitamin B6 parallels the specificity of the transport systems for this vitamin in these organisms. Lactobacillus delbrueckii 7469, however, which specifically requires pyridoxamine-P or pyridoxal-P for growth, accumulates both these compounds and pyridoxine-P from the medium, apparently by active transport, but not pyridoxine, pyridoxamine, or pyridoxal. While pyridoxal-P and pyridoxamine-P are interconvertible in this organism, pyridoxine-P is not further metabolized, thus accounting for the specificity of the growth requirement. These and previous results show (a) that different organisms may employ quite different transport machinery in utilization of a given external nutrient, and (b) that the specificity of the growth requirement for a given form of a vitamin frequently arises from the specificity of transport, but that internal metabolism of the compounds also plays a significant role in some organisms.", "contents": "Transport and metabolism of vitamin B6 in lactic acid bacteria. Streptococcus faecalis 8043 concentrates extracellular [3H]pyridoxal or [3H]pyridoxamine primarily as the corresponding 5'-phosphates. Accumulation of pyridoxamine requires an exogenous energy source and is inhibited by glycolysis inhibitors. A membrane potential is not required for transport of pyridoxamine, and an artificially generated potential does not drive uptake in this organism. Based on this and other evidence, it is concluded that S. faecalis accumulates pyridoxamine by facilitated diffusion in conjunction with trapping by pyridoxal kinase. Pyridoxamine-P is not concentrated, but equilibrates with that provided externally. Lactobacillus casei 7469 concentrates radioactivity only from pyridoxal, which appears internally as pyridoxal-P, suggesting that it too absorbs the vitamin by facilitated diffusion plus trapping. The specificity of the growth requirement of S. faecalis and L. casei for vitamin B6 parallels the specificity of the transport systems for this vitamin in these organisms. Lactobacillus delbrueckii 7469, however, which specifically requires pyridoxamine-P or pyridoxal-P for growth, accumulates both these compounds and pyridoxine-P from the medium, apparently by active transport, but not pyridoxine, pyridoxamine, or pyridoxal. While pyridoxal-P and pyridoxamine-P are interconvertible in this organism, pyridoxine-P is not further metabolized, thus accounting for the specificity of the growth requirement. These and previous results show (a) that different organisms may employ quite different transport machinery in utilization of a given external nutrient, and (b) that the specificity of the growth requirement for a given form of a vitamin frequently arises from the specificity of transport, but that internal metabolism of the compounds also plays a significant role in some organisms."}
{"id": "PMID:14136", "title": "Phosphorylation of cardiac troponin by cyclic adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "The purpose of this investigation was to characterize the phosphorylation of bovine cardiac troponin by cyclic AMP-dependent protein kinase. The purified troponin-tropomyosin complex from beef heart contained 0.78 +/- 0.15 mol of phosphate per mol of protein. Analysis of the isolated protein components indicated that the endogenous phosphate was predominately in the inhibitory subunit (TN-I) and the tropomyosin-binding subunit (TN-T) of troponin. When cardiac troponin or the troponin-tropomyosin complex was incubated with cyclic AMP-dependent protein kinase and [gamma-32P]ATP, the rate of phosphorylation was stimulated by cyclic AMP and inhibited by the heat-stable protein inhibitor of cyclic AMP-dependent protein kinase. The 32P was incorporated specifically into the TN-I subunit with a maximal incorporation of 1 mol of phosphate per mol of protein. The maximal amount of phosphate incorporated did not vary significantly between troponin preparations that contained low or high amounts of endogenous phosphate. The Vmax of the initial rates of phosphorylation with troponin or troponin-tropomyosin as substrates was 3.5-fold greater than the value obtained with unfractionated histones. The rate or extent of phosphorylation was not altered by actin in the presence or absence of Ca2+. The maximal rate of phosphorylation occurred between pH 8.5 and 9.0. At pH 6.0 and 7.0 the maximal rates of phosphorylation were 13 and 45% of that observed at pH 8.5, respectively. These results indicate that cyclic AMP formation in cardiac muscle may be associated with the rapid and specific phosphorylation of the TN-I subunit of troponin. The presence of endogenous phosphate in TN-T and TN-I suggests that kinases other than cyclic AMP-dependent protein kinase may also phosphorylate troponin in vivo.", "contents": "Phosphorylation of cardiac troponin by cyclic adenosine 3':5'-monophosphate-dependent protein kinase. The purpose of this investigation was to characterize the phosphorylation of bovine cardiac troponin by cyclic AMP-dependent protein kinase. The purified troponin-tropomyosin complex from beef heart contained 0.78 +/- 0.15 mol of phosphate per mol of protein. Analysis of the isolated protein components indicated that the endogenous phosphate was predominately in the inhibitory subunit (TN-I) and the tropomyosin-binding subunit (TN-T) of troponin. When cardiac troponin or the troponin-tropomyosin complex was incubated with cyclic AMP-dependent protein kinase and [gamma-32P]ATP, the rate of phosphorylation was stimulated by cyclic AMP and inhibited by the heat-stable protein inhibitor of cyclic AMP-dependent protein kinase. The 32P was incorporated specifically into the TN-I subunit with a maximal incorporation of 1 mol of phosphate per mol of protein. The maximal amount of phosphate incorporated did not vary significantly between troponin preparations that contained low or high amounts of endogenous phosphate. The Vmax of the initial rates of phosphorylation with troponin or troponin-tropomyosin as substrates was 3.5-fold greater than the value obtained with unfractionated histones. The rate or extent of phosphorylation was not altered by actin in the presence or absence of Ca2+. The maximal rate of phosphorylation occurred between pH 8.5 and 9.0. At pH 6.0 and 7.0 the maximal rates of phosphorylation were 13 and 45% of that observed at pH 8.5, respectively. These results indicate that cyclic AMP formation in cardiac muscle may be associated with the rapid and specific phosphorylation of the TN-I subunit of troponin. The presence of endogenous phosphate in TN-T and TN-I suggests that kinases other than cyclic AMP-dependent protein kinase may also phosphorylate troponin in vivo."}
{"id": "PMID:14137", "title": "Solubility and diffusion coefficient of adenosine 3':5'-monophosphate.", "content": "Several previously unavailable parameters of adenosine 3':5'-monophosphate have been determined. The molar extinction coefficient at pH 7.0 is 1.38 X 10(-4), the aqueous solubility at pH 7.0 is 0.0236 M and the diffusion coefficient is 4.44 X 10(-6) cm2/s.", "contents": "Solubility and diffusion coefficient of adenosine 3':5'-monophosphate. Several previously unavailable parameters of adenosine 3':5'-monophosphate have been determined. The molar extinction coefficient at pH 7.0 is 1.38 X 10(-4), the aqueous solubility at pH 7.0 is 0.0236 M and the diffusion coefficient is 4.44 X 10(-6) cm2/s."}
{"id": "PMID:14138", "title": "Steady state kinetics and binding of eukaryotic cytochromes c with yeast cytochrome c peroxidase.", "content": "1. The steady state kinetics for the oxidation of ferrocytochrome c by yeast cytochrome c peroxidase are biphasic under most conditions. The same biphasic kinetics were observed for yeast iso-1, yeast iso-2, horse, tuna, and cicada cytochromes c. On changing ionic strength, buffer anions, and pH, the apparent Km values for the initial phase (Km1) varied relatively little while the corresponding apparent maximal velocities varied over a much larger range. 2. The highest apparent Vmax1 for horse cytochrome c is attained at relatively low pH (congruent to 6.0) and low ionic strength (congruent to 0.05), while maximal activity for the yeast protein is at higher pH (congruent to 7.0) and higher ionic strength (congruent to 0.2), with some variations depending on the nature of the buffering ions. 3. Direct binding studies showed that cytochrome c binds to two sites on the peroxidase, under conditions that give biphasic kinetics. Under those ionic conditions that yield monophasic kinetics, binding occurred at only one site. At the optimal buffer concentrations for both yeast and horse cytochromes c, the KD1 and KD2 values approximate the Km1 and Km2 values. At ionic strengths below optimal, binding becomes too strong and above optimal, too weak. 4. Under ionic conditions that are optimal and give monophasic kinetics with horse cytochrome c but are suboptimal for the yeast protein, yeast cytochrome c strongly inhibits the reaction of horse cytochrome c with peroxidase, uncompetitively at one site and competitively at a second site. The appearance of the second site under monophasic conditions is interpreted as an allosteric effect of the inhibitor binding to the first site. 5. The simplest model accounting for these observations postulates two kinetically active sites on each molecule of peroxidase, a high affinity and a low affinity site, that may correspond to the free radical and the heme iron (IV) of the oxidized enzyme, respectively. Both oxidizing equivalents may be discharged at either site. Furthermore, the enzyme appears to exist as an equilibrium mixture of a high ionic strength form, EH and a low ionic strength form, EL, the former reacting optimally with yeast cytochrome c, and the latter with horse cytochrome c.", "contents": "Steady state kinetics and binding of eukaryotic cytochromes c with yeast cytochrome c peroxidase. 1. The steady state kinetics for the oxidation of ferrocytochrome c by yeast cytochrome c peroxidase are biphasic under most conditions. The same biphasic kinetics were observed for yeast iso-1, yeast iso-2, horse, tuna, and cicada cytochromes c. On changing ionic strength, buffer anions, and pH, the apparent Km values for the initial phase (Km1) varied relatively little while the corresponding apparent maximal velocities varied over a much larger range. 2. The highest apparent Vmax1 for horse cytochrome c is attained at relatively low pH (congruent to 6.0) and low ionic strength (congruent to 0.05), while maximal activity for the yeast protein is at higher pH (congruent to 7.0) and higher ionic strength (congruent to 0.2), with some variations depending on the nature of the buffering ions. 3. Direct binding studies showed that cytochrome c binds to two sites on the peroxidase, under conditions that give biphasic kinetics. Under those ionic conditions that yield monophasic kinetics, binding occurred at only one site. At the optimal buffer concentrations for both yeast and horse cytochromes c, the KD1 and KD2 values approximate the Km1 and Km2 values. At ionic strengths below optimal, binding becomes too strong and above optimal, too weak. 4. Under ionic conditions that are optimal and give monophasic kinetics with horse cytochrome c but are suboptimal for the yeast protein, yeast cytochrome c strongly inhibits the reaction of horse cytochrome c with peroxidase, uncompetitively at one site and competitively at a second site. The appearance of the second site under monophasic conditions is interpreted as an allosteric effect of the inhibitor binding to the first site. 5. The simplest model accounting for these observations postulates two kinetically active sites on each molecule of peroxidase, a high affinity and a low affinity site, that may correspond to the free radical and the heme iron (IV) of the oxidized enzyme, respectively. Both oxidizing equivalents may be discharged at either site. Furthermore, the enzyme appears to exist as an equilibrium mixture of a high ionic strength form, EH and a low ionic strength form, EL, the former reacting optimally with yeast cytochrome c, and the latter with horse cytochrome c."}
{"id": "PMID:14139", "title": "Properties of passive binding of calcium to endoplasmic reticulum from adipocytes.", "content": "Calcium binding to isolated adipocyte microsomes enriched in endoplasmic reticulum has been characterized. Binding was concentration-dependent, saturable, and totally dissociable. Steady state was reached within 20 min at all calcium concentrations tested. Three apparent classes of binding sites were identified in kinetic and steady state studies using calcium concentrations from 1 muM to 10 mM. The affinity constants (and maximum binding capacities) as determined by computer analysis for the three classes were 2.1 X 10(5) M-1 (0.28 nmol of calcium/mg of protein), 1.3 X 10(4) M-1 (1.1 nmol/mg), and 1.3 X 10(2) M-1 (35 nmol/mg). The dissociation rate constants for the high and intermediate affinity classes of sites were 1.6 X 10(-3) S-1, respectively, and the association rate constant for the high affinity sites was 8 X 10(2) M-1 S-1. The affinity constant calculated from the rate constants was 5.0 X 10(5) M-1 for the high affinity sites in agreement with the value obtained in studies at steady state. The three classes of binding sites were specific for calcium. Magnesium was a noncompetitive inhibitor of calcium binding to all three classes of sites with a Ki of 9 to 12 mM. Calcium binding at 1 muM calcium was 50% inhibited by 18 muM La3+, 600 muM Sr2+, or 2.7 mM Ba2+. These data represent the first analysis of passive calcium binding to endoplasmic reticulum from nonmuscular cells and the first report of corresponding rate constants for either endoplasmic or sarcoplasmic reticulum. The characteristics of the binding are consistent with the properties of calcium transport by endoplasmic reticulum of adipocytes. The characteristics and specificity of the calcium binding constitute further evidence that endoplasmic reticulum plays an important role in cellular calcium homeostasis.", "contents": "Properties of passive binding of calcium to endoplasmic reticulum from adipocytes. Calcium binding to isolated adipocyte microsomes enriched in endoplasmic reticulum has been characterized. Binding was concentration-dependent, saturable, and totally dissociable. Steady state was reached within 20 min at all calcium concentrations tested. Three apparent classes of binding sites were identified in kinetic and steady state studies using calcium concentrations from 1 muM to 10 mM. The affinity constants (and maximum binding capacities) as determined by computer analysis for the three classes were 2.1 X 10(5) M-1 (0.28 nmol of calcium/mg of protein), 1.3 X 10(4) M-1 (1.1 nmol/mg), and 1.3 X 10(2) M-1 (35 nmol/mg). The dissociation rate constants for the high and intermediate affinity classes of sites were 1.6 X 10(-3) S-1, respectively, and the association rate constant for the high affinity sites was 8 X 10(2) M-1 S-1. The affinity constant calculated from the rate constants was 5.0 X 10(5) M-1 for the high affinity sites in agreement with the value obtained in studies at steady state. The three classes of binding sites were specific for calcium. Magnesium was a noncompetitive inhibitor of calcium binding to all three classes of sites with a Ki of 9 to 12 mM. Calcium binding at 1 muM calcium was 50% inhibited by 18 muM La3+, 600 muM Sr2+, or 2.7 mM Ba2+. These data represent the first analysis of passive calcium binding to endoplasmic reticulum from nonmuscular cells and the first report of corresponding rate constants for either endoplasmic or sarcoplasmic reticulum. The characteristics of the binding are consistent with the properties of calcium transport by endoplasmic reticulum of adipocytes. The characteristics and specificity of the calcium binding constitute further evidence that endoplasmic reticulum plays an important role in cellular calcium homeostasis."}
{"id": "PMID:14140", "title": "Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse.", "content": "Inbred mice bearing certain alleles at the Mottled locus have defects in connective tissue which result in weakness of skin and of blood vessels. Previous studies have established that cross-links in collagen and elastin are decreased in these animals due to impaired formation of lysine-derived aldehydes. Lysyl oxidase activity in extracts of skin is markedly lower in those prepared from affected animals than control mice. An inhibitor of lysyl oxidase is present in equal amounts in affected and control skins and does not account for diminished activity found in affected animals.", "contents": "Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. Inbred mice bearing certain alleles at the Mottled locus have defects in connective tissue which result in weakness of skin and of blood vessels. Previous studies have established that cross-links in collagen and elastin are decreased in these animals due to impaired formation of lysine-derived aldehydes. Lysyl oxidase activity in extracts of skin is markedly lower in those prepared from affected animals than control mice. An inhibitor of lysyl oxidase is present in equal amounts in affected and control skins and does not account for diminished activity found in affected animals."}
{"id": "PMID:14141", "title": "Different molecular forms of D-ribulose-1,5-bisphosphate carboxylase from Rhodopseudomonas sphaeroides.", "content": "Ribulose-1,5-bisphosphate (Rbu-P2) carboxylase isolated from Rhodopseudomonas sphaeroides 2.4.1.Ga was separated into two different forms by DEAE-cellulose column chromatography. Both forms, designated Peak I and Peak II have been purified to homogeneity by the criterion of polyacrylamide disc-gel electrophoresis. The Peak I carboxylase has a molecular weight of 550,000, while the Peak II carboxylase is a smaller protein having a molecular weight of approximately 360,000. Sodium dodecyl sulfate electrophoresis revealed a large subunit for both enzymes which migrates similarly to the large subunit of spinach Rbu-P2 carboxylase. The Peak I enzyme also exhibited a small subunit having a molecular weight of 11,000. No evidence for a smaller polypeptide was found associated with the Peak II enzyme. Antisera prepared against the Peak I enzyme inhibited Peak I enzymatic activity, but had no effect on the activity of the Peak II enzyme. The two enzymes exhibited marked differences in catalytic properties. The Peak I enzyme exhibits optimal activity at pH 8.0 and is inhibited by low concentrations of 6-phosphogluconate, while the Peak II enzyme has a pH optimum of 7.2 and is relatively insensitive to 6-phosphogluconate.", "contents": "Different molecular forms of D-ribulose-1,5-bisphosphate carboxylase from Rhodopseudomonas sphaeroides. Ribulose-1,5-bisphosphate (Rbu-P2) carboxylase isolated from Rhodopseudomonas sphaeroides 2.4.1.Ga was separated into two different forms by DEAE-cellulose column chromatography. Both forms, designated Peak I and Peak II have been purified to homogeneity by the criterion of polyacrylamide disc-gel electrophoresis. The Peak I carboxylase has a molecular weight of 550,000, while the Peak II carboxylase is a smaller protein having a molecular weight of approximately 360,000. Sodium dodecyl sulfate electrophoresis revealed a large subunit for both enzymes which migrates similarly to the large subunit of spinach Rbu-P2 carboxylase. The Peak I enzyme also exhibited a small subunit having a molecular weight of 11,000. No evidence for a smaller polypeptide was found associated with the Peak II enzyme. Antisera prepared against the Peak I enzyme inhibited Peak I enzymatic activity, but had no effect on the activity of the Peak II enzyme. The two enzymes exhibited marked differences in catalytic properties. The Peak I enzyme exhibits optimal activity at pH 8.0 and is inhibited by low concentrations of 6-phosphogluconate, while the Peak II enzyme has a pH optimum of 7.2 and is relatively insensitive to 6-phosphogluconate."}
{"id": "PMID:14142", "title": "Proton inactivation of Ca2+ transport by sarcoplasmic reticulum.", "content": "The effects of acid on fragmented sarcoplasmic reticulum from rabbit white skeletal muscle have been studied. Brief exposure of sarcoplasmic reticulum membranes to pH values in the range 5.5 to 6.0 at 37 degrees caused rapid inactivation of calcium accumulation measured at 25 degrees in the presence of oxalate (calcium uptake) while (Ca2+, Mg2+)-ATPase (EC 3.6.1.3) activity was enhanced by 75%. ATPase activity, measured at 37 degrees in the absence of oxalate and in the calcium steady state, was unaltered when calcium uptake was inactivated. Calcium efflux from sarcoplasmic reticulum vesicles, previously loaded passibely with 45CaCl2, was only slightly increased when calcium uptake was abolished. At still lower pH values, 5.0 to 5.5, (Ca2+, Mg2+)-ATPase was inactivated while Mg2+ ATPase was more acid-resistant. Acid inactivation of calcium uptake followed simple first order kinetics for at least 80% of the time course. The rate constant, k, increased from 0.043 min-1 to 1.63 min-1 between pH 6.50 and pH 5.35. At pH 4.65, Ea, the energy of activation, was 31 kcal mol-1 between 24 degrees and 43 degrees. Inactivation, once initiated, was irreversible. Aged suspensions of sarcoplasmic reticulum were more sensitive to acid inactivation. Ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid enhanced inactivation, and calcium specifically protected against inactivation with half-maximal effect at 1 to 2 mM. The sulfhydryl reagent, dithiothreitol (1 mM), caused significantly increased rates of inactivation. Calcium binding was studied by dual wavelength spectrophotometry and stopped flow analysis. Acid inactivation distinguished two ATP-induced binding sites, previously described (Entman, M. L., Snow, T. R., Freed, D., and Schwartz, A. (1973) J. Biol. Chem. 248, 7762-7772) as a superficial Mg2+-independent Site A which binds and releases calcium rapidly and a deeper Mg2+-dependent Site B which binds and releases calcium more slowly. Rates of binding to both sites were decreased by acid inactivation. Binding of calcium to Site A increased, however, from 4.6 to 6.4 nmol mg of protein-1 whereas that to Site B decreased from 17.0 to 6.9 nmol mg of protein-1. Passive binding of calcium to sites of medium affinity (K = 7 X 10(4) M-1) was unaffected by acid inactivation of calcium uptake. Temperature dependence of (Ca2+, Mg2+)-ATPase was unchanged in the range 9-34 degrees. Above 34 degrees, the higher activation energy process (Ealpha = 33.7 kcal mol-1) observed in control sarcoplasmic reticulum and thought to arise from a conformational change in the ATPase (Inesi, G., Millman, M., and Eletr, S. (1973) J. Mol. Biol. 81, 483-504) was diminished by acid inactivation (Ealpha = 8.2 kcal mol-1) in a manner suggesting that it is related to active calcium transport. The ATP in equilibrium 32Pi exchange reaction was diminished by acid, but 25% of the activity remained when calcium uptake was completely abolished...", "contents": "Proton inactivation of Ca2+ transport by sarcoplasmic reticulum. The effects of acid on fragmented sarcoplasmic reticulum from rabbit white skeletal muscle have been studied. Brief exposure of sarcoplasmic reticulum membranes to pH values in the range 5.5 to 6.0 at 37 degrees caused rapid inactivation of calcium accumulation measured at 25 degrees in the presence of oxalate (calcium uptake) while (Ca2+, Mg2+)-ATPase (EC 3.6.1.3) activity was enhanced by 75%. ATPase activity, measured at 37 degrees in the absence of oxalate and in the calcium steady state, was unaltered when calcium uptake was inactivated. Calcium efflux from sarcoplasmic reticulum vesicles, previously loaded passibely with 45CaCl2, was only slightly increased when calcium uptake was abolished. At still lower pH values, 5.0 to 5.5, (Ca2+, Mg2+)-ATPase was inactivated while Mg2+ ATPase was more acid-resistant. Acid inactivation of calcium uptake followed simple first order kinetics for at least 80% of the time course. The rate constant, k, increased from 0.043 min-1 to 1.63 min-1 between pH 6.50 and pH 5.35. At pH 4.65, Ea, the energy of activation, was 31 kcal mol-1 between 24 degrees and 43 degrees. Inactivation, once initiated, was irreversible. Aged suspensions of sarcoplasmic reticulum were more sensitive to acid inactivation. Ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid enhanced inactivation, and calcium specifically protected against inactivation with half-maximal effect at 1 to 2 mM. The sulfhydryl reagent, dithiothreitol (1 mM), caused significantly increased rates of inactivation. Calcium binding was studied by dual wavelength spectrophotometry and stopped flow analysis. Acid inactivation distinguished two ATP-induced binding sites, previously described (Entman, M. L., Snow, T. R., Freed, D., and Schwartz, A. (1973) J. Biol. Chem. 248, 7762-7772) as a superficial Mg2+-independent Site A which binds and releases calcium rapidly and a deeper Mg2+-dependent Site B which binds and releases calcium more slowly. Rates of binding to both sites were decreased by acid inactivation. Binding of calcium to Site A increased, however, from 4.6 to 6.4 nmol mg of protein-1 whereas that to Site B decreased from 17.0 to 6.9 nmol mg of protein-1. Passive binding of calcium to sites of medium affinity (K = 7 X 10(4) M-1) was unaffected by acid inactivation of calcium uptake. Temperature dependence of (Ca2+, Mg2+)-ATPase was unchanged in the range 9-34 degrees. Above 34 degrees, the higher activation energy process (Ealpha = 33.7 kcal mol-1) observed in control sarcoplasmic reticulum and thought to arise from a conformational change in the ATPase (Inesi, G., Millman, M., and Eletr, S. (1973) J. Mol. Biol. 81, 483-504) was diminished by acid inactivation (Ealpha = 8.2 kcal mol-1) in a manner suggesting that it is related to active calcium transport. The ATP in equilibrium 32Pi exchange reaction was diminished by acid, but 25% of the activity remained when calcium uptake was completely abolished..."}
{"id": "PMID:14143", "title": "Podophyllotoxin as a probe for the colchicine binding site of tubulin.", "content": "The binding of [3H]podophyllotoxin to tubulin, measured by a DEAE-cellulose filter paper method, occurs with an affinity constant of 1.8 X 10(6) M-1 (37 degrees at pH 6.7). Like colchicine, approximately 0.8 mol of podophyllotixin are bound per mol of tubulin dimer, and the reaction is entropy-driven (43 cal deg-1 mol-1). At 37 degrees the association rate constant for podophyllotoxin binding is 3.8 X 10(6) M-1 h-1, approximtaely 10 times higher than for colchicine; this is reflected in the activation energies for binding which are 14.7 kcal/mol for podophyllotoxin and 20.3 kcal/mol for colchicine. The dissociation rate constant for the tubulin-podophyllotoxin complex is 1.9 h-1, and the affinity constant calculated from the ratio of the rates is close to that obtained by equilibrium measurements. Podophyllotxin and colchicine are mutually competitive inhibitors. This can be ascribed to the fact that both compounds have a trimethoxyphenyl ring and analogues of either compound with bulky substituents in their trimethoxyphenyl moiety are unable to inhibit the the binding of either of the two ligands. Tropolone, which inhibits colchicine binding competitively, has no effect on the podophyllotoxin/tubulin reaction. Conversely, podophyllotoxin does not influence tropolone binding. Moreover, the tropolone binding site of tubulin does not show the temperature and pH lability of the colchicine and podophyllotoxin domains, hence this lability can be ascribed to the trimethoxyphenyl binding region of tubulin. Since podophyllotoxin analogues with a modified B ring do not bind, it is concluded that both podophyllotoxin and colchicine each have at least two points of attachment to tubulin and that they share one of them, the binding region of the trimethoxyphenyl moiety.", "contents": "Podophyllotoxin as a probe for the colchicine binding site of tubulin. The binding of [3H]podophyllotoxin to tubulin, measured by a DEAE-cellulose filter paper method, occurs with an affinity constant of 1.8 X 10(6) M-1 (37 degrees at pH 6.7). Like colchicine, approximately 0.8 mol of podophyllotixin are bound per mol of tubulin dimer, and the reaction is entropy-driven (43 cal deg-1 mol-1). At 37 degrees the association rate constant for podophyllotoxin binding is 3.8 X 10(6) M-1 h-1, approximtaely 10 times higher than for colchicine; this is reflected in the activation energies for binding which are 14.7 kcal/mol for podophyllotoxin and 20.3 kcal/mol for colchicine. The dissociation rate constant for the tubulin-podophyllotoxin complex is 1.9 h-1, and the affinity constant calculated from the ratio of the rates is close to that obtained by equilibrium measurements. Podophyllotxin and colchicine are mutually competitive inhibitors. This can be ascribed to the fact that both compounds have a trimethoxyphenyl ring and analogues of either compound with bulky substituents in their trimethoxyphenyl moiety are unable to inhibit the the binding of either of the two ligands. Tropolone, which inhibits colchicine binding competitively, has no effect on the podophyllotoxin/tubulin reaction. Conversely, podophyllotoxin does not influence tropolone binding. Moreover, the tropolone binding site of tubulin does not show the temperature and pH lability of the colchicine and podophyllotoxin domains, hence this lability can be ascribed to the trimethoxyphenyl binding region of tubulin. Since podophyllotoxin analogues with a modified B ring do not bind, it is concluded that both podophyllotoxin and colchicine each have at least two points of attachment to tubulin and that they share one of them, the binding region of the trimethoxyphenyl moiety."}
{"id": "PMID:14144", "title": "Purification and properties of galactokinase from Saccharomyces cerevisiae.", "content": "Galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase) was purified to homogeneity with a 50% yield from cells of Saccharomyces cerevisiae which were fully induced for the production of the galactose metabolizing enzymes. The purification was accomplished by:(a) ammonium sulfate fractionation, (b) streptomycin sulfate precipitation. (c) DEAE-cellulose chromatography, (d) hydroxylapatite chromatography, and finally (e) Bio-Gel A-0.5 m gel filtration. The resulting preparation of galactokinase was judged to be at least 95% pure by the following criteria: (a) sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (b) ultracentrifuge analysis, (c) nondissociating polyacrylamide gel electrophoresis, and (d) Bio-Gel A-0.5 m gel filtration. The purified enzyme preparation was used to determine the Km values for the two substrates, galactose and ATP, which were found to be 0.60 and 0.15 mM, respectively. Vmax was also determined and found to be 3.35 mmol/h/mg. This corresponds to a turnover rate of 3350 molecules of galactose phosphorylated/min/enzyme molecule. The effect of pH on the galactokinase-catalyzed phosphorylation of galactose was determined; the results showed the pH optimum of the reaction to be in the range of pH 8.0 to 9.0. The enzyme is highly specific for galactose since galactokinase did not appear to phosphorylate any of the other sugars tested at a rate greater than 0.5% of the rate of galactose phosphorylation. Amino acid analysis was performed on the enzyme preparation and the results were used to calculate the partial specific volume (v) of 0.736. The NH2-terminal sequence was determined for the first 3 residues. The molecular weight and subunit composition were determined by ultracentrifugation and polyacrylamide gel electrophoresis under dissociating and nondissociating conditions. The data obtained indicated that galactokinase is a monomeric protein of molecular weight 58,000.", "contents": "Purification and properties of galactokinase from Saccharomyces cerevisiae. Galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase) was purified to homogeneity with a 50% yield from cells of Saccharomyces cerevisiae which were fully induced for the production of the galactose metabolizing enzymes. The purification was accomplished by:(a) ammonium sulfate fractionation, (b) streptomycin sulfate precipitation. (c) DEAE-cellulose chromatography, (d) hydroxylapatite chromatography, and finally (e) Bio-Gel A-0.5 m gel filtration. The resulting preparation of galactokinase was judged to be at least 95% pure by the following criteria: (a) sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (b) ultracentrifuge analysis, (c) nondissociating polyacrylamide gel electrophoresis, and (d) Bio-Gel A-0.5 m gel filtration. The purified enzyme preparation was used to determine the Km values for the two substrates, galactose and ATP, which were found to be 0.60 and 0.15 mM, respectively. Vmax was also determined and found to be 3.35 mmol/h/mg. This corresponds to a turnover rate of 3350 molecules of galactose phosphorylated/min/enzyme molecule. The effect of pH on the galactokinase-catalyzed phosphorylation of galactose was determined; the results showed the pH optimum of the reaction to be in the range of pH 8.0 to 9.0. The enzyme is highly specific for galactose since galactokinase did not appear to phosphorylate any of the other sugars tested at a rate greater than 0.5% of the rate of galactose phosphorylation. Amino acid analysis was performed on the enzyme preparation and the results were used to calculate the partial specific volume (v) of 0.736. The NH2-terminal sequence was determined for the first 3 residues. The molecular weight and subunit composition were determined by ultracentrifugation and polyacrylamide gel electrophoresis under dissociating and nondissociating conditions. The data obtained indicated that galactokinase is a monomeric protein of molecular weight 58,000."}
{"id": "PMID:14145", "title": "Characterization of liver cholic acid coenzyme A ligase activity. Evidence that separate microsomal enzymes are responsible for cholic acid and fatty acid activation.", "content": "Investigations on the cholic acid CoA ligase activity of rat liver microsomes were made possible by the development of a rapid, sensitive radiochemical assay based on the conversion of [3H]choloyl-CoA. More than 70% of the rat liver cholic acid CoA ligase activity was associated with the microsomal subcellular fraction. The dependencies of cholic acid CoA ligase activity on pH, ATP, CoA, Triton WR-1339, acetone, ethanol, magnesium, and salts were investigated. The hypothesis that the long chain fatty acid CoA ligase activity and the cholic acid CoA ligase activity are catalyzed by a single microsomal enzyme was investigated. The ATP, CoA, and cholic (palmitic) acid kinetics neither supported nor negated the hypothesis. Cholic acid was not an inhibitor of the fatty acid CoA ligase and palmitic acid was not a competitive inhibitor of the cholic acid CoA ligase. The cholic acid CoA ligase activity utilized dATP as a substrate more effectively than did the fatty acid CoA ligase activity. The cholic acid and fatty acid CoA ligase activities appeared to have different pH dependencies, differed in thermolability at 41 degrees, and were differentially inactivated by phospholipase C. Moreover, fatty acid CoA ligase activity was present in microsomal fractions from all rat organs tested while cholic acid CoA ligase activity was detected only in liver microsomes. The data suggest that separate microsomal enzymes are responsible for the cholic acid and the fatty acid CoA ligase activities in liver.", "contents": "Characterization of liver cholic acid coenzyme A ligase activity. Evidence that separate microsomal enzymes are responsible for cholic acid and fatty acid activation. Investigations on the cholic acid CoA ligase activity of rat liver microsomes were made possible by the development of a rapid, sensitive radiochemical assay based on the conversion of [3H]choloyl-CoA. More than 70% of the rat liver cholic acid CoA ligase activity was associated with the microsomal subcellular fraction. The dependencies of cholic acid CoA ligase activity on pH, ATP, CoA, Triton WR-1339, acetone, ethanol, magnesium, and salts were investigated. The hypothesis that the long chain fatty acid CoA ligase activity and the cholic acid CoA ligase activity are catalyzed by a single microsomal enzyme was investigated. The ATP, CoA, and cholic (palmitic) acid kinetics neither supported nor negated the hypothesis. Cholic acid was not an inhibitor of the fatty acid CoA ligase and palmitic acid was not a competitive inhibitor of the cholic acid CoA ligase. The cholic acid CoA ligase activity utilized dATP as a substrate more effectively than did the fatty acid CoA ligase activity. The cholic acid and fatty acid CoA ligase activities appeared to have different pH dependencies, differed in thermolability at 41 degrees, and were differentially inactivated by phospholipase C. Moreover, fatty acid CoA ligase activity was present in microsomal fractions from all rat organs tested while cholic acid CoA ligase activity was detected only in liver microsomes. The data suggest that separate microsomal enzymes are responsible for the cholic acid and the fatty acid CoA ligase activities in liver."}
{"id": "PMID:14146", "title": "Human endonuclease specific for apurinic/apyrimidinic sites in DNA. Partial purification and characterization of multiple forms from placenta.", "content": "Six chromatographically distinct forms of endonuclease active on apurinic and apyrimidinic sites in DNA have been purified away from DNA phosphatases, DNA N-glycosidases, and other DNases of human placenta. The forms seem to be monomeric proteins of 27,000 to 31,000 daltons, and although catalytically similar, they can be distinguished from one another on the basis of substrate Km and the effects of small molecules such as ATP. Analysis of enzymatic activity on a spectrum of damaged DNA substrates indicates that the enzyme forms probably act at an appreciable rate only adjacent to the phosphodiester bond of a deoxyribose lacking a base (purine or pyrimidine) in duplex DNA; such sites can be formed by treating the DNA with acid, alkylating agents, DNA N-glycosidases, and, probably, x-rays and OsO4. The incision is made so as to form a deoxyribose 5'-phosphate and a 3'-hydroxynucleotide.", "contents": "Human endonuclease specific for apurinic/apyrimidinic sites in DNA. Partial purification and characterization of multiple forms from placenta. Six chromatographically distinct forms of endonuclease active on apurinic and apyrimidinic sites in DNA have been purified away from DNA phosphatases, DNA N-glycosidases, and other DNases of human placenta. The forms seem to be monomeric proteins of 27,000 to 31,000 daltons, and although catalytically similar, they can be distinguished from one another on the basis of substrate Km and the effects of small molecules such as ATP. Analysis of enzymatic activity on a spectrum of damaged DNA substrates indicates that the enzyme forms probably act at an appreciable rate only adjacent to the phosphodiester bond of a deoxyribose lacking a base (purine or pyrimidine) in duplex DNA; such sites can be formed by treating the DNA with acid, alkylating agents, DNA N-glycosidases, and, probably, x-rays and OsO4. The incision is made so as to form a deoxyribose 5'-phosphate and a 3'-hydroxynucleotide."}
{"id": "PMID:14147", "title": "Effect of aspartate on complexes between glutamate dehydrogenase and various aminotransferases.", "content": "In previous studies it was found that: (a) aspartate aminotransferase increases the aspartate dehydrogenase activity of glutamate dehydrogenase; (b) the pyridoxamine-P form of this aminotransferase can form an enzyme-enzyme complex with glutamate dehydrogenase; and (c) the pyridoxamine-P form can be dehydrogenated to the pyridoxal-P form by glutamate dehydrogenase. It was therefore concluded (Fahien, L.A., and Smith, S.E. (1974) J. Biol. Chem 249, 2696-2703) that in the aspartate dehydrogenase reaction, aspartate converts the aminotransferase into the pyridoxamine-P form which is then dehydrogenated by glutamate dehydrogenase. The present results support this mechanism and essentially exclude the possibility that aspartate actually reacts with glutamate dehydrogenase and the aminotransferase is an allosteric activator. Indeed, it was found that aspartate is actually an activator of the reaction between glutamate dehydrogenase and the pyridoxamine-P form of the aminotransferase. Aspartate also markedly activated the alanine dehydrogenase reaction catalyzed by glutamate dehydrogenase plus alanine aminotransferase and the ornithine dehydrogenase reaction catalyzed by ornithine aminotransferase plus glutamate dehydrogenase. In these latter two reactions, there is no significant conversion of aspartate to oxalecetate and other compounds tested (including oxalacetate) would not substitute for aspartate. Thus aspartate is apparently bound to glutamate dehydrogenase and this increases the reactivity of this enzyme with the pyridoxamine-P form of aminotransferases. This could be of physiological importance because aspartate enables the aspartate and ornithine dehydrogenase reactions to be catalyzed almost as rapidly by complexes between glutamate dehydrogenase and the appropriate mitochondrial aminotransferase in the absence of alpha-ketoglutarate as they are in the presence of this substrate. Furthermore, in the presence of aspartate, alpha-ketoglutarate can have little or no affect on these reactions. Consequently, in the mitochondria of some organs these reactions could be catalyzed exclusively by enzyme-enzyme complexes even in the presence of alpha-ketoglutarate. Rat liver glutamate dehydrogenase is essentially as active as thebovine liver enzyme with aminotransferases. Since the rat liver enzyme does not polymerize, this unambiguously demonstrates that monomeric forms of glutamate dehydrogenase can react with aminotransferases.", "contents": "Effect of aspartate on complexes between glutamate dehydrogenase and various aminotransferases. In previous studies it was found that: (a) aspartate aminotransferase increases the aspartate dehydrogenase activity of glutamate dehydrogenase; (b) the pyridoxamine-P form of this aminotransferase can form an enzyme-enzyme complex with glutamate dehydrogenase; and (c) the pyridoxamine-P form can be dehydrogenated to the pyridoxal-P form by glutamate dehydrogenase. It was therefore concluded (Fahien, L.A., and Smith, S.E. (1974) J. Biol. Chem 249, 2696-2703) that in the aspartate dehydrogenase reaction, aspartate converts the aminotransferase into the pyridoxamine-P form which is then dehydrogenated by glutamate dehydrogenase. The present results support this mechanism and essentially exclude the possibility that aspartate actually reacts with glutamate dehydrogenase and the aminotransferase is an allosteric activator. Indeed, it was found that aspartate is actually an activator of the reaction between glutamate dehydrogenase and the pyridoxamine-P form of the aminotransferase. Aspartate also markedly activated the alanine dehydrogenase reaction catalyzed by glutamate dehydrogenase plus alanine aminotransferase and the ornithine dehydrogenase reaction catalyzed by ornithine aminotransferase plus glutamate dehydrogenase. In these latter two reactions, there is no significant conversion of aspartate to oxalecetate and other compounds tested (including oxalacetate) would not substitute for aspartate. Thus aspartate is apparently bound to glutamate dehydrogenase and this increases the reactivity of this enzyme with the pyridoxamine-P form of aminotransferases. This could be of physiological importance because aspartate enables the aspartate and ornithine dehydrogenase reactions to be catalyzed almost as rapidly by complexes between glutamate dehydrogenase and the appropriate mitochondrial aminotransferase in the absence of alpha-ketoglutarate as they are in the presence of this substrate. Furthermore, in the presence of aspartate, alpha-ketoglutarate can have little or no affect on these reactions. Consequently, in the mitochondria of some organs these reactions could be catalyzed exclusively by enzyme-enzyme complexes even in the presence of alpha-ketoglutarate. Rat liver glutamate dehydrogenase is essentially as active as thebovine liver enzyme with aminotransferases. Since the rat liver enzyme does not polymerize, this unambiguously demonstrates that monomeric forms of glutamate dehydrogenase can react with aminotransferases."}
{"id": "PMID:14148", "title": "Interaction of thyroid peroxidase with concanavalin A covalently coupled to agarose.", "content": "We have investigated the interaction between concanavalin A-agarose (Con A-agarose) and thyroid peroxidase, an integral membrane protein found in the 105,000 X g, 1-h particulate fraction of thyroid tissue. An intact form of porcine thyroid peroxidase was obtained by solubilization with the nonionic detergent Triton X-100 and two fragmented, hydrophilic forms of the enzyme were prepared by trypsin treatment of the membrane. The three types of thyroid peroxidase bind to Con A-agarose and can be eluted with alpha-methyl-D-mannoside. The alpha-methyl-D-mannoside eluate of the most purified thyroid peroxidase preparation has been analyzed by polyacrylamide gel electrophoresis. Peroxidase activity corresponds with a glycoprotein band. The binding of thyroid peroxidase to Con A-agarose can be inhibited by sugars in the following order: alpha-methyl-D-mannoside greater than D-mannose greater than alpha-methyl-D-glucoside greater than D-glucose greater than D-galactose. This order of specificity is typical of Con A-sugar interactions. Furthermore, inactivation of the carbohydrate binding site of Con A by demetallization greatly reduces the extent of thyroid peroxidase binding. Reactivation of the carbohydrate binding site by the addition of Ca2+ and Mn2+ to demetallized Con A-agarose restores thyroid peroxidase binding. These and other experiments suggest that htyroid peroxidase is, like several other peroxidases, a glycoprotein. In addition, the interaction between thyroid peroxidase and Con A-agarose may provide a new purification tool for thyroid peroxidase.", "contents": "Interaction of thyroid peroxidase with concanavalin A covalently coupled to agarose. We have investigated the interaction between concanavalin A-agarose (Con A-agarose) and thyroid peroxidase, an integral membrane protein found in the 105,000 X g, 1-h particulate fraction of thyroid tissue. An intact form of porcine thyroid peroxidase was obtained by solubilization with the nonionic detergent Triton X-100 and two fragmented, hydrophilic forms of the enzyme were prepared by trypsin treatment of the membrane. The three types of thyroid peroxidase bind to Con A-agarose and can be eluted with alpha-methyl-D-mannoside. The alpha-methyl-D-mannoside eluate of the most purified thyroid peroxidase preparation has been analyzed by polyacrylamide gel electrophoresis. Peroxidase activity corresponds with a glycoprotein band. The binding of thyroid peroxidase to Con A-agarose can be inhibited by sugars in the following order: alpha-methyl-D-mannoside greater than D-mannose greater than alpha-methyl-D-glucoside greater than D-glucose greater than D-galactose. This order of specificity is typical of Con A-sugar interactions. Furthermore, inactivation of the carbohydrate binding site of Con A by demetallization greatly reduces the extent of thyroid peroxidase binding. Reactivation of the carbohydrate binding site by the addition of Ca2+ and Mn2+ to demetallized Con A-agarose restores thyroid peroxidase binding. These and other experiments suggest that htyroid peroxidase is, like several other peroxidases, a glycoprotein. In addition, the interaction between thyroid peroxidase and Con A-agarose may provide a new purification tool for thyroid peroxidase."}
{"id": "PMID:14149", "title": "Translation of albumin messenger RNA in a cell-free protein-synthesizing system derived from wheat germ.", "content": "Purified rat liver albumin mRNA directed the synthesis of albumin in a mRNA-dependent cell-free protein-synthesizing system derived from wheat germ extracts. The [3H]leucine-labeled in vitro translation product reacted with antibodies specific for albumin and co-migrated with authentic 14C-labeled serum albumin during gel electrophoresis in the presence or absence of sodium dodecyl sufate. Higher concentrations of potassium and magnesium ions were required for the translation of albumin mRNA than for total liver mRNAs. These requirements were consistent for the purified albumin as well as when it was a component in the liver mRNA mixture. At the higher potassium or magnesium concentrations, only intact albumin molecules were synthesized, whereas lower concentrations of these ions caused the production of antibody-reactive fragments. These fragments were apparently the result of premature termination of peptide synthesis and not due to endogenous proteolytic activity.", "contents": "Translation of albumin messenger RNA in a cell-free protein-synthesizing system derived from wheat germ. Purified rat liver albumin mRNA directed the synthesis of albumin in a mRNA-dependent cell-free protein-synthesizing system derived from wheat germ extracts. The [3H]leucine-labeled in vitro translation product reacted with antibodies specific for albumin and co-migrated with authentic 14C-labeled serum albumin during gel electrophoresis in the presence or absence of sodium dodecyl sufate. Higher concentrations of potassium and magnesium ions were required for the translation of albumin mRNA than for total liver mRNAs. These requirements were consistent for the purified albumin as well as when it was a component in the liver mRNA mixture. At the higher potassium or magnesium concentrations, only intact albumin molecules were synthesized, whereas lower concentrations of these ions caused the production of antibody-reactive fragments. These fragments were apparently the result of premature termination of peptide synthesis and not due to endogenous proteolytic activity."}
{"id": "PMID:14150", "title": "Stimulation of human platelet guanylate cyclase by fatty acids.", "content": "Guanylate cyclase from human platelets was over 90% soluble, even when assayed in the presence of Triton X-100. A time-dependent increase in activity occurred when the enzyme was incubated at 37 degrees and this spontaneous activation was prevented by dithiothreitol. Arachidonic acid stimulated the soluble enzyme activity approximately 2- to 3-fold. Linear double reciprocal plots of guanylate cyclase activation as a function of arachidonic acid concentration were obtained with a Ka value of 2.1 muM. A Hill coefficient of 0.98 was obtained indicating that one fatty acid binding site is present for each catalytic site. Concentrations of arachidonic acid in excess of 10 muM caused less than maximal stimulation. Dihomo-gamma-linolenic acid and two polyunsaturated 22 carbon fatty acids stimulated the activity of guanylate cyclase to the same degree as did arachidonic acid. The methyl ester of arachidonic acid was much less effective. Diene, monoene, and saturated fatty acids of various carbon chain lengths as well as prostaglandins E1, E2, and F2alpha, had little or no effect. These data indicate that the structural determined required for stimulation by fatty acids of soluble platelet guanylate cyclase is a 1,4,7-octatriene group with its first double bond in the omega6 position. This structural group is similar to the substrate specificity determinants of fatty acid cyclooxygenase, the first enzyme of the prostaglandin synthetase complex. However, conversion of arachidonic acid to a metabolite of the cyclooxygenase pathway did not appear to be required for activation of the cyclase since activation occurred in the 105,000 X g supernatant fraction and pretreatment of this fraction with aspirin did not alter the ability of arachidonic acid to activate guanylate cyclase. Kinetic studies showed that the stimulation of guanylate cyclase by arachidonic acid is primarily an effect on maximal velocity. Arachidonic acid did not alter the concentration of free Mn2+ required for optimal activity. It is concluded that the activity of the soluble form of guanylate cyclase in cell-free preparations of human platelets can be increased by a lipid-protein interaction involving specific polyunsaturated fatty acids.", "contents": "Stimulation of human platelet guanylate cyclase by fatty acids. Guanylate cyclase from human platelets was over 90% soluble, even when assayed in the presence of Triton X-100. A time-dependent increase in activity occurred when the enzyme was incubated at 37 degrees and this spontaneous activation was prevented by dithiothreitol. Arachidonic acid stimulated the soluble enzyme activity approximately 2- to 3-fold. Linear double reciprocal plots of guanylate cyclase activation as a function of arachidonic acid concentration were obtained with a Ka value of 2.1 muM. A Hill coefficient of 0.98 was obtained indicating that one fatty acid binding site is present for each catalytic site. Concentrations of arachidonic acid in excess of 10 muM caused less than maximal stimulation. Dihomo-gamma-linolenic acid and two polyunsaturated 22 carbon fatty acids stimulated the activity of guanylate cyclase to the same degree as did arachidonic acid. The methyl ester of arachidonic acid was much less effective. Diene, monoene, and saturated fatty acids of various carbon chain lengths as well as prostaglandins E1, E2, and F2alpha, had little or no effect. These data indicate that the structural determined required for stimulation by fatty acids of soluble platelet guanylate cyclase is a 1,4,7-octatriene group with its first double bond in the omega6 position. This structural group is similar to the substrate specificity determinants of fatty acid cyclooxygenase, the first enzyme of the prostaglandin synthetase complex. However, conversion of arachidonic acid to a metabolite of the cyclooxygenase pathway did not appear to be required for activation of the cyclase since activation occurred in the 105,000 X g supernatant fraction and pretreatment of this fraction with aspirin did not alter the ability of arachidonic acid to activate guanylate cyclase. Kinetic studies showed that the stimulation of guanylate cyclase by arachidonic acid is primarily an effect on maximal velocity. Arachidonic acid did not alter the concentration of free Mn2+ required for optimal activity. It is concluded that the activity of the soluble form of guanylate cyclase in cell-free preparations of human platelets can be increased by a lipid-protein interaction involving specific polyunsaturated fatty acids."}
{"id": "PMID:14151", "title": "3-Hydroxy-3-methylgutaryl-CoA synthase. Participation of acetyl-S-enzyme and enzyme-S-hydroxymethylgutaryl-SCoA intermediates in the reaction.", "content": "Acetyl-CoA reacts stoichiometrically with a cysteinyl sufhydryl group of avian liver 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase to yield acetyl-S-enzyme (Miziorko H.M., Clinkenbeard, K.D., Reed, W.D., and Lane, M.D. (1975) J. Biol. Chem. 250, 5768-5773). Evidence that acetyl-S-enzyme condenses with the second substrate, acetoacetyl CoA, to form enzyme-S-HMG-SCoA has been obtained by trapping and characterizing this putative intermediate. [14C]Acetyl-S-enzyme was incubated briefly at -25 degrees with acetoacetyl-CoA, precipitated with trichloroacetic acid, and the labeled acylated enzyme species were isolated. Performic acid oxidation of the precipitated [14C]acyl-S-enzyme intermediates produced volatile [14C]acetic acid from unreacted [14C]acetyl-S-enzyme and nonvolatile [14C]3-hydroxy-3-methyl glutaric acid from enzyme-S-[14C]HMG-SCoA. Condensation of unlabeled acetyl-S-enzyme with [14C]aceto-acetyl-CoA or acetoacetyl-[3H]CoA also produced labeled enzyme-S-HMG-SCoA. Thus, the acetyl moiety from acetyl-CoA and the acetoacetyl and CoA moieties from acetoacetyl-CoA all are incorporated into the HMG-CoA which is covalently-linked to the enzyme. Enzyme-S-[14C]HMG-SCoA was subjected to proteolytic digestion under conditions favorable for intramolecular S to N acyl transfer in the predicted cysteine-S-[14C]HMG-SCoA fragment. Performic acid oxidation of the protease-digested material yields N-[14C]HMG-cysteic acid indicating that HMG-CoA had been covalently bound to the enzyme via the -SH of an active site cysteine. An isotope trapping technique was employed to test the kinetic competence of acetyl-S-enzyme as an intermediate in the HMG-CoA synthase-catalyzed reaction. Evidence is presented which indicates that the rate of condensation of acetoacetyl-CoA with acetyl-S-enzyme to form enzyme-S-HMG-SCoA is more rapid than either the acetylation of the synthase by acetyl-CoA or the overall forward reaction leading to HMG-CoA. These observations, together with indirect evidence that hydrolysis of enzyme-S-HMG-SCoA is extremely rapid, suggest that acetylation of synthase is the rate-limiting step in HMG-CoA synthesis.", "contents": "3-Hydroxy-3-methylgutaryl-CoA synthase. Participation of acetyl-S-enzyme and enzyme-S-hydroxymethylgutaryl-SCoA intermediates in the reaction. Acetyl-CoA reacts stoichiometrically with a cysteinyl sufhydryl group of avian liver 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase to yield acetyl-S-enzyme (Miziorko H.M., Clinkenbeard, K.D., Reed, W.D., and Lane, M.D. (1975) J. Biol. Chem. 250, 5768-5773). Evidence that acetyl-S-enzyme condenses with the second substrate, acetoacetyl CoA, to form enzyme-S-HMG-SCoA has been obtained by trapping and characterizing this putative intermediate. [14C]Acetyl-S-enzyme was incubated briefly at -25 degrees with acetoacetyl-CoA, precipitated with trichloroacetic acid, and the labeled acylated enzyme species were isolated. Performic acid oxidation of the precipitated [14C]acyl-S-enzyme intermediates produced volatile [14C]acetic acid from unreacted [14C]acetyl-S-enzyme and nonvolatile [14C]3-hydroxy-3-methyl glutaric acid from enzyme-S-[14C]HMG-SCoA. Condensation of unlabeled acetyl-S-enzyme with [14C]aceto-acetyl-CoA or acetoacetyl-[3H]CoA also produced labeled enzyme-S-HMG-SCoA. Thus, the acetyl moiety from acetyl-CoA and the acetoacetyl and CoA moieties from acetoacetyl-CoA all are incorporated into the HMG-CoA which is covalently-linked to the enzyme. Enzyme-S-[14C]HMG-SCoA was subjected to proteolytic digestion under conditions favorable for intramolecular S to N acyl transfer in the predicted cysteine-S-[14C]HMG-SCoA fragment. Performic acid oxidation of the protease-digested material yields N-[14C]HMG-cysteic acid indicating that HMG-CoA had been covalently bound to the enzyme via the -SH of an active site cysteine. An isotope trapping technique was employed to test the kinetic competence of acetyl-S-enzyme as an intermediate in the HMG-CoA synthase-catalyzed reaction. Evidence is presented which indicates that the rate of condensation of acetoacetyl-CoA with acetyl-S-enzyme to form enzyme-S-HMG-SCoA is more rapid than either the acetylation of the synthase by acetyl-CoA or the overall forward reaction leading to HMG-CoA. These observations, together with indirect evidence that hydrolysis of enzyme-S-HMG-SCoA is extremely rapid, suggest that acetylation of synthase is the rate-limiting step in HMG-CoA synthesis."}
{"id": "PMID:14152", "title": "Characterization and kinetics of native and chemically acitvated human liver alcohol dehydrogenases.", "content": "Acetimidylation of the amino groups of alcohol dehydrogenase from human and horse liver yields several modified enzyme forms, which differ in electrophoretic mobility and can be separated by ion exchange chromatography, but which are similar in kinetic characteristics. The acetimidylated, as well as the methylated, enzymes from human livers of the normal phenotype have increased activity and larger Michaelis and inhibition constants. These results suggest that the human enzyme has amino groups at the active sites, as was shown previously for the horse enzyme. The variant subunit occuring in the enzyme isolated from atypical human livers does not seem to be activated by acetimidylation, which may indicate that substitution of proline for Ala-230 or modifiction of Lys-228 is sufficient to fully activate the enzyme. Results of product inhibition studies of native and modified human enzymes are consistent with an Ordered Bi Bi mechanism. However, the major isoenzyme of native human liver alcohol, dehydrogenase exhibits nonlinear kinetics over a wide range of ethanol concentrations. This result may indicate that subunits with different kinetic characteristics are present or that there is negative cooperativity between subunits. After chemical modification, the kinetic patterns become linear, suggesting that the mechanism is altered.", "contents": "Characterization and kinetics of native and chemically acitvated human liver alcohol dehydrogenases. Acetimidylation of the amino groups of alcohol dehydrogenase from human and horse liver yields several modified enzyme forms, which differ in electrophoretic mobility and can be separated by ion exchange chromatography, but which are similar in kinetic characteristics. The acetimidylated, as well as the methylated, enzymes from human livers of the normal phenotype have increased activity and larger Michaelis and inhibition constants. These results suggest that the human enzyme has amino groups at the active sites, as was shown previously for the horse enzyme. The variant subunit occuring in the enzyme isolated from atypical human livers does not seem to be activated by acetimidylation, which may indicate that substitution of proline for Ala-230 or modifiction of Lys-228 is sufficient to fully activate the enzyme. Results of product inhibition studies of native and modified human enzymes are consistent with an Ordered Bi Bi mechanism. However, the major isoenzyme of native human liver alcohol, dehydrogenase exhibits nonlinear kinetics over a wide range of ethanol concentrations. This result may indicate that subunits with different kinetic characteristics are present or that there is negative cooperativity between subunits. After chemical modification, the kinetic patterns become linear, suggesting that the mechanism is altered."}
{"id": "PMID:14153", "title": "A new large form of transcarboxylase with six outer subunits and twelve biotinyl carboxyl carrier subunits.", "content": "A new form of transcarboxylase has been isolated which has a molecular weight of 1,200,000, an s20,w of 26 S, and contains 12 biotinyl groups. Transcarboxylase as isolated previously has a molecular weight of 790,000, an s20,w of 18 S, and contains six biotinyl groups. The larger species of enzyme consists of a central hexameric subunit with six dimeric outer subunits attached to it by biotinyl carboxyl carrier proteins, three each at the opposite faces of the central subunits. This larger species is stable at pH 5.5, but dissociates to the 18 S species at pH values near neutrality with loss of a set of three of the outer subunits with two of the biotinyl carboxyl carrier proteins still attached to each of these subunits. The dissociation to the 18 S form occurs by several rapidly reversible steps and under certain conditions of centrifugation multiple peaks are observed as a consequence of the occurrence of different forms of enzyme with variable numbers of the outer subunits attached to the 18 S enzyme. The s20,w value of the so-called 26 S enzyme varies with conditions. Isolated 18 S enzyme has been combined with isolated outer subunits to form active 26 S enzyme. The newly enzyme is a normal form but has not been isolated previously because of its dissociation to the 18 S form at neutral pH. A procedure is described for the isolation of the 26 S form in a highly purified state. The molecular weight of the enzyme has been determined by high speed meniscus depletion. In addition, a procedure is described for dissociation of the 26 S form of the enzyme and isolation of the resulting outer subunits with the biotinyl subunits still attached to it. Evidence is presented that all six outer subunits participate in the enzymatic reaction which includes the demonstration that; (a) all 12 biotins of the 26 S form of the enzyme can be carboxylated with [3-14C]methylmalonyl coenzyme A; (b) there is an increase in enzymatic activity when the outer subunits are combined with the normal 18 S enzyme with formation of the 26 S enzyme; and (c) a 26 S form of the enzyme is active which is prepared by combination of inactive 18 S trypsin-treated transcarboxylase with the outer subunits. The trypsin-treated 18 S enzyme is inactive because trypsin removes the biotin as biotinyl peptides and the 26 S enzyme is active because of the second set of active outer subunits.", "contents": "A new large form of transcarboxylase with six outer subunits and twelve biotinyl carboxyl carrier subunits. A new form of transcarboxylase has been isolated which has a molecular weight of 1,200,000, an s20,w of 26 S, and contains 12 biotinyl groups. Transcarboxylase as isolated previously has a molecular weight of 790,000, an s20,w of 18 S, and contains six biotinyl groups. The larger species of enzyme consists of a central hexameric subunit with six dimeric outer subunits attached to it by biotinyl carboxyl carrier proteins, three each at the opposite faces of the central subunits. This larger species is stable at pH 5.5, but dissociates to the 18 S species at pH values near neutrality with loss of a set of three of the outer subunits with two of the biotinyl carboxyl carrier proteins still attached to each of these subunits. The dissociation to the 18 S form occurs by several rapidly reversible steps and under certain conditions of centrifugation multiple peaks are observed as a consequence of the occurrence of different forms of enzyme with variable numbers of the outer subunits attached to the 18 S enzyme. The s20,w value of the so-called 26 S enzyme varies with conditions. Isolated 18 S enzyme has been combined with isolated outer subunits to form active 26 S enzyme. The newly enzyme is a normal form but has not been isolated previously because of its dissociation to the 18 S form at neutral pH. A procedure is described for the isolation of the 26 S form in a highly purified state. The molecular weight of the enzyme has been determined by high speed meniscus depletion. In addition, a procedure is described for dissociation of the 26 S form of the enzyme and isolation of the resulting outer subunits with the biotinyl subunits still attached to it. Evidence is presented that all six outer subunits participate in the enzymatic reaction which includes the demonstration that; (a) all 12 biotins of the 26 S form of the enzyme can be carboxylated with [3-14C]methylmalonyl coenzyme A; (b) there is an increase in enzymatic activity when the outer subunits are combined with the normal 18 S enzyme with formation of the 26 S enzyme; and (c) a 26 S form of the enzyme is active which is prepared by combination of inactive 18 S trypsin-treated transcarboxylase with the outer subunits. The trypsin-treated 18 S enzyme is inactive because trypsin removes the biotin as biotinyl peptides and the 26 S enzyme is active because of the second set of active outer subunits."}
{"id": "PMID:14154", "title": "Transient kinetic and deuterium isotope effect studies on the catalytic mechanism of phosphoglycerate dehydrogenase.", "content": "The catalytic mechanism of the phosphoglycerate dehydrogenase reaction in both directions was investigated by studying: (a) pre-steady state transients in reduced coenzyme appearance or disappearance or disappearance and in protein fluorescence; (b) deuterium isotope effects on the transients and on the steady state reactions; and (c) the partial reaction between the enzyme-NADH complex and hydroxypyruvate-P. These studies led to the scheme below for the ternary complex interconversion. E1-NADH-hydroxypyruvate-P(1)equilibriumE2-NADH-hydroxypyruvate-P(2)equilibriumE3-NADH-hydroxypyruvate-P + H+(3)equilibriumE3-NAD+-3-phosphoglycerate(4)equilibriumE4-NAD+-3-phosphoglycerate Steps 1,2, and 4 are ternary complex isomerizations. Step 3 is the hydride transfer. Under steady state conditions isomerization 2 is the rate-determining step in the direction of hydroxypyruvate-P reduction at higher pH values. At lower pH values, the hydride transfer step is also partially rate-determining. The rate-determining step in the direction of 3-phosphoglycerate oxidation occurs subsequent to the hydride transfer step at higher pH values. At lower pH values the rate is determined by both isomerization 4 and the hydride transfer step. Isomerizations 1, 2, and 4 were inhibited by serine, an allosteric inhibitor, indicating that the inactive conformation of the enzyme is incapable of performing any of the steps of the ternary complex interconversion. Phosphoglycerate dehydrogenase corresponds to a V-type allosteric enzyme. When the enzyme-NADH complex was mixed with hydroxypyruvate-P at pH 8.5, a rapid quenching of enzymebound NADH fluorescence occurred. This process was studied under pseudo-first order conditions and shown to be the result of hydroxypyruvate-P binding.", "contents": "Transient kinetic and deuterium isotope effect studies on the catalytic mechanism of phosphoglycerate dehydrogenase. The catalytic mechanism of the phosphoglycerate dehydrogenase reaction in both directions was investigated by studying: (a) pre-steady state transients in reduced coenzyme appearance or disappearance or disappearance and in protein fluorescence; (b) deuterium isotope effects on the transients and on the steady state reactions; and (c) the partial reaction between the enzyme-NADH complex and hydroxypyruvate-P. These studies led to the scheme below for the ternary complex interconversion. E1-NADH-hydroxypyruvate-P(1)equilibriumE2-NADH-hydroxypyruvate-P(2)equilibriumE3-NADH-hydroxypyruvate-P + H+(3)equilibriumE3-NAD+-3-phosphoglycerate(4)equilibriumE4-NAD+-3-phosphoglycerate Steps 1,2, and 4 are ternary complex isomerizations. Step 3 is the hydride transfer. Under steady state conditions isomerization 2 is the rate-determining step in the direction of hydroxypyruvate-P reduction at higher pH values. At lower pH values, the hydride transfer step is also partially rate-determining. The rate-determining step in the direction of 3-phosphoglycerate oxidation occurs subsequent to the hydride transfer step at higher pH values. At lower pH values the rate is determined by both isomerization 4 and the hydride transfer step. Isomerizations 1, 2, and 4 were inhibited by serine, an allosteric inhibitor, indicating that the inactive conformation of the enzyme is incapable of performing any of the steps of the ternary complex interconversion. Phosphoglycerate dehydrogenase corresponds to a V-type allosteric enzyme. When the enzyme-NADH complex was mixed with hydroxypyruvate-P at pH 8.5, a rapid quenching of enzymebound NADH fluorescence occurred. This process was studied under pseudo-first order conditions and shown to be the result of hydroxypyruvate-P binding."}
{"id": "PMID:14155", "title": "A novel approach to the identification of surface receptors. The use of photosensitive hetero-bifunctional cross-linking reagent.", "content": "Methyl 4-azidobenzoimidate, a photosensitive hetero-bifunctional cross-linking reagent, was synthesized and characterized. This reagent has an imidoester at one end, which reacts spontaneously with primary amines, and an arylazide at the other end, which reacts with a variety of chemical groups upon photolysis by ultraviolet radiation. The reagent molecules were attached to concanavalin A by reactions between imidoester groups of the reagents and free amino groups of the lectin. These activated lectins were purified on a Sephadex G-25 column and showed the binding affinity to an affinity column, glucosylated Sepharose, and to the human erythrocyte ghost membrane. The activated lectins were incubated with the membranes and then unbound lectins were removed by washing. The lectins bound to receptors in the membranes were irradiated with a shortwave ultraviolet lamp to photolyze arylazides attached to the lectins, thus cross-linking the lectins and receptors together. Then the membranes were solubilized and electrophoresed. On gels, the intensity of the lectin receptor band diminished slightly and concomitantly a new band of a higher molecular weight appeared. When 125I-labeled concanavalin A was used, the new band contained the radioactivity. The extent of the appearance of the new band and the decrease of the receptor band were reduced significantly when the ultraviolet irradiation was omitted or the activated lectins were incubated with the membranes in the presence of the lectin inhibitor, alpha-methylmannoside. The irradiation of nonactivated, receptor-bound concanavalin A did not cause those changes. When the activated lectins alone were irradiated with ultraviolet, the band of the lectin dimer appeared whereas nonirradiated lectins appeared mostly as monomers. It is concluded that a small fraction of the activated lectins were cross-linked to receptors in the membrane upon photolysis. In this study, only 8 reagent molecules were attached to a tetramer of the lectin, compared with the presence of approximately 40 available free amino groups. The efficiency of such cross-links of ligands to receptors may be increased by employing longer versions of the hetero-bifunctional cross-linking reagents and also by attaching more of the reagent molecule to ligands.", "contents": "A novel approach to the identification of surface receptors. The use of photosensitive hetero-bifunctional cross-linking reagent. Methyl 4-azidobenzoimidate, a photosensitive hetero-bifunctional cross-linking reagent, was synthesized and characterized. This reagent has an imidoester at one end, which reacts spontaneously with primary amines, and an arylazide at the other end, which reacts with a variety of chemical groups upon photolysis by ultraviolet radiation. The reagent molecules were attached to concanavalin A by reactions between imidoester groups of the reagents and free amino groups of the lectin. These activated lectins were purified on a Sephadex G-25 column and showed the binding affinity to an affinity column, glucosylated Sepharose, and to the human erythrocyte ghost membrane. The activated lectins were incubated with the membranes and then unbound lectins were removed by washing. The lectins bound to receptors in the membranes were irradiated with a shortwave ultraviolet lamp to photolyze arylazides attached to the lectins, thus cross-linking the lectins and receptors together. Then the membranes were solubilized and electrophoresed. On gels, the intensity of the lectin receptor band diminished slightly and concomitantly a new band of a higher molecular weight appeared. When 125I-labeled concanavalin A was used, the new band contained the radioactivity. The extent of the appearance of the new band and the decrease of the receptor band were reduced significantly when the ultraviolet irradiation was omitted or the activated lectins were incubated with the membranes in the presence of the lectin inhibitor, alpha-methylmannoside. The irradiation of nonactivated, receptor-bound concanavalin A did not cause those changes. When the activated lectins alone were irradiated with ultraviolet, the band of the lectin dimer appeared whereas nonirradiated lectins appeared mostly as monomers. It is concluded that a small fraction of the activated lectins were cross-linked to receptors in the membrane upon photolysis. In this study, only 8 reagent molecules were attached to a tetramer of the lectin, compared with the presence of approximately 40 available free amino groups. The efficiency of such cross-links of ligands to receptors may be increased by employing longer versions of the hetero-bifunctional cross-linking reagents and also by attaching more of the reagent molecule to ligands."}
{"id": "PMID:14156", "title": "Caclium uptake and associated adenosine triphosphatase activity in fragmented sarcoplasmic reticulum. Requirement for potassium ions.", "content": "The effects of monovalent cations on calcium uptake by fragmented sarcoplasmic reticulum have been clarified. Homogenization of muscle tissue in salt-containing solutions leads to contamination of this subcellular fraction with actomyosin and mitochondrial membranes. When, in addition, inorganic cations are contributed by the microsomal suspension and in association with nucleotide triphosphate substrates there is an apparent inhibition of the calcium transport system by potassium and other cations. However, when purified preparations were obtained after homogenization in sucrose medium followed by centrifugation on a sucrose density gradient in a zonal rotor, calcium uptake and the associated adenosine triphosphatase activity were considerably activated by potassium and other univalent cations. When plotted against the log of the free calcium concentration there was only a slight increase in calcium uptake and ATPase activity in the absence of potassium ions but sigmoid-shaped curves were obtained in 100 mM K+ with half-maximal stimulation occurring at 2 muM Ca2+ for both calcium uptake and ATPase activity. The augmentation in calcium uptake was not due to an ionic strength effect as Tris cation at pH 6.6 was shown to be inactive in this respect. Other monovalent cations were effective in the order K+ greater than Na+ greater than NH4+=Rb+=Cs+ greater than Li+ with half-maximal stimulation in 11 mM K+, 16 mM Na+, 25 mM NH4+, Rb+, and Cs+ and in 50 mM Li+. There was nos synergistic action between K+ AND Na+ ions and both calcium uptak and associated ATPase were insensitive to ouabain. Thallous ions  stimulate many K+-requiring enzymes and at one-tenth the concentration were nearly as effective as K+ ions in promoting calcium uptake. The ratio of Ca2+ ions transported to P1 released remained unchanged at 2 after addition of K+ ions indicating an effect on the rate of calcium uptake rather than an increased efficiency of uptake. In support of this it was found that during the stimulation of calcium uptake by Na+ ions there was a reduction in the steady state concentration of phosphorylated intermediate formed from [gamma-32P]ATP. It is considered that there is a physiological requirement for potassium ions in the relaxation process.", "contents": "Caclium uptake and associated adenosine triphosphatase activity in fragmented sarcoplasmic reticulum. Requirement for potassium ions. The effects of monovalent cations on calcium uptake by fragmented sarcoplasmic reticulum have been clarified. Homogenization of muscle tissue in salt-containing solutions leads to contamination of this subcellular fraction with actomyosin and mitochondrial membranes. When, in addition, inorganic cations are contributed by the microsomal suspension and in association with nucleotide triphosphate substrates there is an apparent inhibition of the calcium transport system by potassium and other cations. However, when purified preparations were obtained after homogenization in sucrose medium followed by centrifugation on a sucrose density gradient in a zonal rotor, calcium uptake and the associated adenosine triphosphatase activity were considerably activated by potassium and other univalent cations. When plotted against the log of the free calcium concentration there was only a slight increase in calcium uptake and ATPase activity in the absence of potassium ions but sigmoid-shaped curves were obtained in 100 mM K+ with half-maximal stimulation occurring at 2 muM Ca2+ for both calcium uptake and ATPase activity. The augmentation in calcium uptake was not due to an ionic strength effect as Tris cation at pH 6.6 was shown to be inactive in this respect. Other monovalent cations were effective in the order K+ greater than Na+ greater than NH4+=Rb+=Cs+ greater than Li+ with half-maximal stimulation in 11 mM K+, 16 mM Na+, 25 mM NH4+, Rb+, and Cs+ and in 50 mM Li+. There was nos synergistic action between K+ AND Na+ ions and both calcium uptak and associated ATPase were insensitive to ouabain. Thallous ions  stimulate many K+-requiring enzymes and at one-tenth the concentration were nearly as effective as K+ ions in promoting calcium uptake. The ratio of Ca2+ ions transported to P1 released remained unchanged at 2 after addition of K+ ions indicating an effect on the rate of calcium uptake rather than an increased efficiency of uptake. In support of this it was found that during the stimulation of calcium uptake by Na+ ions there was a reduction in the steady state concentration of phosphorylated intermediate formed from [gamma-32P]ATP. It is considered that there is a physiological requirement for potassium ions in the relaxation process."}
{"id": "PMID:14157", "title": "Purification and properties of the urea amidolyase from Candida utilis.", "content": "Urea amidolyase was purified to homogeneity from extracts of Candida utilis. The purification involves protamine sulfate precipitation, ammonium sulfate precipitation, polyethylene glycol precipitation, Sepharose 6B gel filtration, DEAE-cellulose column chromatography, and hydroxylapatite column chromatography. The final preparation is pure as judged by disc-gel electrophoresis. The molecular weight of urea amidolyase, as determined by gel filtration and disc-gel electrophoresis, is between 500,000 and 520,000. Treatment with sodium dodecyl sulfate results in two peptides with molecular weights of 70,000 and 170,000. The urea carboxylase and allophanate hydrolase activities of urea amidolyase may be distinguished from one another on the basis of (a) the effect of the stabilizers, urea and glycerol, (b) the effect of storage pH on activity, and (c) selective inhibition by sulfhydryl reagents.", "contents": "Purification and properties of the urea amidolyase from Candida utilis. Urea amidolyase was purified to homogeneity from extracts of Candida utilis. The purification involves protamine sulfate precipitation, ammonium sulfate precipitation, polyethylene glycol precipitation, Sepharose 6B gel filtration, DEAE-cellulose column chromatography, and hydroxylapatite column chromatography. The final preparation is pure as judged by disc-gel electrophoresis. The molecular weight of urea amidolyase, as determined by gel filtration and disc-gel electrophoresis, is between 500,000 and 520,000. Treatment with sodium dodecyl sulfate results in two peptides with molecular weights of 70,000 and 170,000. The urea carboxylase and allophanate hydrolase activities of urea amidolyase may be distinguished from one another on the basis of (a) the effect of the stabilizers, urea and glycerol, (b) the effect of storage pH on activity, and (c) selective inhibition by sulfhydryl reagents."}
{"id": "PMID:14158", "title": "Mechanisms of acylation of chymotrypsin by phenyl esters of benzoic acid and acetic acid.", "content": "The kinetics of the acylation of alpha-chymotrypsin by a series of substituted phenyl p-nitrobenzoates have been studied by stopped flow and conventional spectrophotometry. Electron withdrawal in the leaving group accelerates the rate of acylation, and the p value obtained for eight esters is +1.96. The pH- and pD-independent acylation rate constants are, respectively, 1.40 X 10(4) M-1S-1 and 1.23 X 10(4) M-1S-1 for p-nitrophenyl p-nitrobenzoate, and, respectively, 2.19 X 10(3) M-1S-1 and 1968 X 10(3) M-1S-1 for p-nitrophenyl benzoate at 25 degrees. An analysis of structure-reactivity results and kinetic solvent isotope effects indicates a mechanism for acylation by phenylbenzoates in which initial reaction is a nucleophilic attack by an imidazole of the enzyme (His 57). Subsequently, there is rapid transfer of the acylating group to the serine 195 from the acylimidazole species. The kinetic solvent isotope effects for acylation by p-nitrophenyl phenyl acetate and p-nitrophenyl phenyl acetate and p-nitrophenyl hydrocinnamate, in 5%, v/v, acetonitrile, are 1.3 and 2.0, respectively. The latter ester is inhibited more than is p-nitrophenyl benzoate when 5%, v/v, dioxane is substituted for 5%, v/v, acetonitrile as co-solvent. In the presence of 5%, v/v, dioxane a change in the kinetic solvent isotope effect to 1.7 is found for p-nitrophenyl benzoate and p-nitrophenyl phenylacetate while that for the analogous hysdrocinnamate ester is unaffected. The results for the latter substrate are in accord with a general base-catalysed mechanism. Electron-withdrawal groups in the phenyl ring of phenyl acetates accelerate the enzyme acylation yielding a leaving group p of 2.05. The kinetic solvent isotope effects for acylation by p-nitrophenyl thiolacetate and by p-nitrophenyl acetate are close to 2.0. The mechanism of acylation of chymotrypsin by phenyl acetates is not unambiguously defined using these data.", "contents": "Mechanisms of acylation of chymotrypsin by phenyl esters of benzoic acid and acetic acid. The kinetics of the acylation of alpha-chymotrypsin by a series of substituted phenyl p-nitrobenzoates have been studied by stopped flow and conventional spectrophotometry. Electron withdrawal in the leaving group accelerates the rate of acylation, and the p value obtained for eight esters is +1.96. The pH- and pD-independent acylation rate constants are, respectively, 1.40 X 10(4) M-1S-1 and 1.23 X 10(4) M-1S-1 for p-nitrophenyl p-nitrobenzoate, and, respectively, 2.19 X 10(3) M-1S-1 and 1968 X 10(3) M-1S-1 for p-nitrophenyl benzoate at 25 degrees. An analysis of structure-reactivity results and kinetic solvent isotope effects indicates a mechanism for acylation by phenylbenzoates in which initial reaction is a nucleophilic attack by an imidazole of the enzyme (His 57). Subsequently, there is rapid transfer of the acylating group to the serine 195 from the acylimidazole species. The kinetic solvent isotope effects for acylation by p-nitrophenyl phenyl acetate and p-nitrophenyl phenyl acetate and p-nitrophenyl hydrocinnamate, in 5%, v/v, acetonitrile, are 1.3 and 2.0, respectively. The latter ester is inhibited more than is p-nitrophenyl benzoate when 5%, v/v, dioxane is substituted for 5%, v/v, acetonitrile as co-solvent. In the presence of 5%, v/v, dioxane a change in the kinetic solvent isotope effect to 1.7 is found for p-nitrophenyl benzoate and p-nitrophenyl phenylacetate while that for the analogous hysdrocinnamate ester is unaffected. The results for the latter substrate are in accord with a general base-catalysed mechanism. Electron-withdrawal groups in the phenyl ring of phenyl acetates accelerate the enzyme acylation yielding a leaving group p of 2.05. The kinetic solvent isotope effects for acylation by p-nitrophenyl thiolacetate and by p-nitrophenyl acetate are close to 2.0. The mechanism of acylation of chymotrypsin by phenyl acetates is not unambiguously defined using these data."}
{"id": "PMID:14159", "title": "Endonuclease V of Escherichia coli.", "content": "A small endodeoxyribonuclease )2.3 S) that is active on single-stranded DNA has been extensively purified from Escherichia coli so as to be free of other known DNases. It has an alkaline pH optimum (9.5), requires Mg2+, and makes 3'-hydroxy and 5'-phosphate termini. The nuclease nicks duplex DNA, particularly if treated with OsO4, irradiated with ultraviolet light, or exposed to pH 5. The uracil-containing duplex DNA from the Bacillus subtilis phage PBS-2 is an especially good substrate; it is made acid-soluble by levels of the enzyme which fail to produce any acid-soluble material in other single-stranded or duplex DNAs. Neither RNA nor RNA-DNA hybrid are degraded by the enzyme. The enzyme specificity suggests that it might act at abnormal regions in DNA, so that its in vivo function could be to initiate an excision repair sequence. Its high activity on uracil-containing DNA could imply that the enzyme provides an alternative mechanism for excising uracil residues from DNA to the pathway utilizing uracil-DNA N-glycosidase. We suggest that this enzyme be designated as endonuclease V of E. coli.", "contents": "Endonuclease V of Escherichia coli. A small endodeoxyribonuclease )2.3 S) that is active on single-stranded DNA has been extensively purified from Escherichia coli so as to be free of other known DNases. It has an alkaline pH optimum (9.5), requires Mg2+, and makes 3'-hydroxy and 5'-phosphate termini. The nuclease nicks duplex DNA, particularly if treated with OsO4, irradiated with ultraviolet light, or exposed to pH 5. The uracil-containing duplex DNA from the Bacillus subtilis phage PBS-2 is an especially good substrate; it is made acid-soluble by levels of the enzyme which fail to produce any acid-soluble material in other single-stranded or duplex DNAs. Neither RNA nor RNA-DNA hybrid are degraded by the enzyme. The enzyme specificity suggests that it might act at abnormal regions in DNA, so that its in vivo function could be to initiate an excision repair sequence. Its high activity on uracil-containing DNA could imply that the enzyme provides an alternative mechanism for excising uracil residues from DNA to the pathway utilizing uracil-DNA N-glycosidase. We suggest that this enzyme be designated as endonuclease V of E. coli."}
{"id": "PMID:14160", "title": "Human angiotensinogen. Purification partial characterization, and a comparison with animal prohormones.", "content": "The renin-angiotensin system appears to play a major role in the regulation of sodium excretion and fluid intake in a wide variety of animal species from mammals to teleosts. In mammals the system has evolved further importance in terms of blood pressure homeostasis. This hormonal system in all species appears to involve a serum protein prohormone, angiotensinogen, a proteolytic enzyme, renin, and angiotensin I, the decapeptide product of the reaction between renin and angiotensinogen. The importance of this system to the organism appears to correlate directly with the necessity to conserve sodium while an abnormality of this process may underlie the development of hypertension in man. As the starting point of the system, angiotensinogen assumes special importance as a possible index of evolutionary development. In addition, it has been known for many years that human (viz. primate) angiotensinogen differs from that found in other mammals in its inability to be a substrate for animal renins while animal angiotensinogens readily react with human renin. Thus, the enzymatic specificity appears to reside with the prohormone. The biochemical basis for this difference is unresolved due primarily to the lack of purified human angiotensinogen. In this paper we describe methods for the purification of human angiotensinogen which have direct applicability to animal angiotensinogens. Our approach utilizes ammonium sulfate precipitation, Sephadex G-150 chromatography, multiple isoelectric focusing, and concanavalin A-Sepharose affinity chromatography. With the availability of highly purified human angiotensinogen we compared the molecular weights, heterogeneity, isoelectric points, and thermal lability of hog, rabbit, and human angiotensinogen in order to define the biochemical basis of the species variation in renin reactivity...", "contents": "Human angiotensinogen. Purification partial characterization, and a comparison with animal prohormones. The renin-angiotensin system appears to play a major role in the regulation of sodium excretion and fluid intake in a wide variety of animal species from mammals to teleosts. In mammals the system has evolved further importance in terms of blood pressure homeostasis. This hormonal system in all species appears to involve a serum protein prohormone, angiotensinogen, a proteolytic enzyme, renin, and angiotensin I, the decapeptide product of the reaction between renin and angiotensinogen. The importance of this system to the organism appears to correlate directly with the necessity to conserve sodium while an abnormality of this process may underlie the development of hypertension in man. As the starting point of the system, angiotensinogen assumes special importance as a possible index of evolutionary development. In addition, it has been known for many years that human (viz. primate) angiotensinogen differs from that found in other mammals in its inability to be a substrate for animal renins while animal angiotensinogens readily react with human renin. Thus, the enzymatic specificity appears to reside with the prohormone. The biochemical basis for this difference is unresolved due primarily to the lack of purified human angiotensinogen. In this paper we describe methods for the purification of human angiotensinogen which have direct applicability to animal angiotensinogens. Our approach utilizes ammonium sulfate precipitation, Sephadex G-150 chromatography, multiple isoelectric focusing, and concanavalin A-Sepharose affinity chromatography. With the availability of highly purified human angiotensinogen we compared the molecular weights, heterogeneity, isoelectric points, and thermal lability of hog, rabbit, and human angiotensinogen in order to define the biochemical basis of the species variation in renin reactivity..."}
{"id": "PMID:14162", "title": "Studies of individual carbon sites of hen egg white lysozyme by natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Assignment of the nonprotonated aromatic carbon resonances to specific residues in the sequence.", "content": "The resonances of nonprotonated aromatic carbons in natural abundance 13C NMR spectra of hen egg white lysozyme are assigned to specific residues of the amino acid sequence. Chemical shift considerations, the effect of pH, and partially relaxed Fourier transform NMR spectra are used to assign each resonance to one of the seven types of nonprotonated aromatic carbons of amino acid residues. Spectra of chemically modified lysozyme samples yield various assignments to specific residues in the sequence. Line-broadening effects caused by binding of the relaxation probes Gd3+ and 4-N-acetamido-2,2,6,6-tetramethylipiperidine-1-oxyl yield specific assignments which are fully consistent with those based on chemical modifications. The effects of paramagnetic shift reagents and amino sugar inhibitors do not yield any obvious specific assignments. The effect of pH on the chemical shift of Cgamma of His-15 yields a pKalpha in agreement with published values, and indicates that the imidazole form of His-15 exists mainly (or entirely) as the Nepsilon3-H tautomer. The effect of pH on the chemical shifts (measured up to pH 8.8, at 38 degrees) of Czeta and Cgamma of the 3 tyrosine residues yields crude pKalpha values of 9.5 and 10 for Tyr-23 and one of the other tyrosines, respectively. The 3rd tyrosine residue does not exhibit titration behavior.", "contents": "Studies of individual carbon sites of hen egg white lysozyme by natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Assignment of the nonprotonated aromatic carbon resonances to specific residues in the sequence. The resonances of nonprotonated aromatic carbons in natural abundance 13C NMR spectra of hen egg white lysozyme are assigned to specific residues of the amino acid sequence. Chemical shift considerations, the effect of pH, and partially relaxed Fourier transform NMR spectra are used to assign each resonance to one of the seven types of nonprotonated aromatic carbons of amino acid residues. Spectra of chemically modified lysozyme samples yield various assignments to specific residues in the sequence. Line-broadening effects caused by binding of the relaxation probes Gd3+ and 4-N-acetamido-2,2,6,6-tetramethylipiperidine-1-oxyl yield specific assignments which are fully consistent with those based on chemical modifications. The effects of paramagnetic shift reagents and amino sugar inhibitors do not yield any obvious specific assignments. The effect of pH on the chemical shift of Cgamma of His-15 yields a pKalpha in agreement with published values, and indicates that the imidazole form of His-15 exists mainly (or entirely) as the Nepsilon3-H tautomer. The effect of pH on the chemical shifts (measured up to pH 8.8, at 38 degrees) of Czeta and Cgamma of the 3 tyrosine residues yields crude pKalpha values of 9.5 and 10 for Tyr-23 and one of the other tyrosines, respectively. The 3rd tyrosine residue does not exhibit titration behavior."}
{"id": "PMID:14163", "title": "Participation of tryptophan 62 in the self-association of hen egg white lysozyme. Application of natural abundance carbon 13 nuclear magnetic resonance spectroscopy.", "content": "Self-association of hen egg white lysozyme in solution of 38 degrees) is examined by means of natural abundance 13C nuclear magnetic resonance spectroscopy. The effect of pH on the resonances of the nonprotonated aromatic carbons of 9 mM lysozyme, and the effect of protein concentration (at pH 7) on these resonances, both indicate that self-association significantly affects the chemical shift of Cgamma of Trp-62, but not the chemical shifts of the other nonprotonated aromatic carbons. This result is consistent with the reported participation of Trp-62 in the intermolecular contact (Banerjee, S.K., Pogolotti, A., and Rupley, J.A. (1975) J. Biol. Chem. 250, 8260-8266). Our results indicate that the resonance of Cgamma or Trp-62 is a convenient monitor of lysozyme self-association. The chemical shift of this resonance reflects the extent of aggregation, while the line width yields information about the lifetime of the intermolecular contact. This lifetime is 1 to 2 ms at 38 degrees (9 mM protein, 0.1 M NaCl, pH 7). Our results also indicate that self-association of lysozyme is not accompanied by any general conformational change, and that binding of a lanthanide ion (at the metal ion binding site near the carboxylate groups of ASP-52 AND Glu-35) strongly suppresses self-association.", "contents": "Participation of tryptophan 62 in the self-association of hen egg white lysozyme. Application of natural abundance carbon 13 nuclear magnetic resonance spectroscopy. Self-association of hen egg white lysozyme in solution of 38 degrees) is examined by means of natural abundance 13C nuclear magnetic resonance spectroscopy. The effect of pH on the resonances of the nonprotonated aromatic carbons of 9 mM lysozyme, and the effect of protein concentration (at pH 7) on these resonances, both indicate that self-association significantly affects the chemical shift of Cgamma of Trp-62, but not the chemical shifts of the other nonprotonated aromatic carbons. This result is consistent with the reported participation of Trp-62 in the intermolecular contact (Banerjee, S.K., Pogolotti, A., and Rupley, J.A. (1975) J. Biol. Chem. 250, 8260-8266). Our results indicate that the resonance of Cgamma or Trp-62 is a convenient monitor of lysozyme self-association. The chemical shift of this resonance reflects the extent of aggregation, while the line width yields information about the lifetime of the intermolecular contact. This lifetime is 1 to 2 ms at 38 degrees (9 mM protein, 0.1 M NaCl, pH 7). Our results also indicate that self-association of lysozyme is not accompanied by any general conformational change, and that binding of a lanthanide ion (at the metal ion binding site near the carboxylate groups of ASP-52 AND Glu-35) strongly suppresses self-association."}
{"id": "PMID:14165", "title": "Galactosyl transferase of a Golgi fraction from cultured neoplastic mast cells.", "content": "Suspension cultures of neoplastic mouse mast cells were used to obtain large quantities of a homogeneous cell population as starting material for cell fractionation. A Golgi fraction was prepared by slight modification of established techniques and identified by electron microscopy. Assay of galactosyl transferase activity using ovalbumin, desialylated degalactosylated orosomucoid, and N-acetylglucosamine as galactose acceptors showed that the Golgi fraction was enriched in specific activity over the homogenate. The Golgi galactosyl transferase was examined in detail. Acceptor concentrations for optimal galactose incorporation were determined, and substrate inhibition effects were shown with higher concentrations of all three acceptors. Manganese was shown to be necessary for galactose incorporation. A higher concentration of manganese afforded some protection from substrate inhibition by acceptors, but at the same time was itself inhibitory. All three acceptors competed with one another for galactose incorporation, indicating that a single enzyme catalyzed the transfer of galactose for all acceptors.", "contents": "Galactosyl transferase of a Golgi fraction from cultured neoplastic mast cells. Suspension cultures of neoplastic mouse mast cells were used to obtain large quantities of a homogeneous cell population as starting material for cell fractionation. A Golgi fraction was prepared by slight modification of established techniques and identified by electron microscopy. Assay of galactosyl transferase activity using ovalbumin, desialylated degalactosylated orosomucoid, and N-acetylglucosamine as galactose acceptors showed that the Golgi fraction was enriched in specific activity over the homogenate. The Golgi galactosyl transferase was examined in detail. Acceptor concentrations for optimal galactose incorporation were determined, and substrate inhibition effects were shown with higher concentrations of all three acceptors. Manganese was shown to be necessary for galactose incorporation. A higher concentration of manganese afforded some protection from substrate inhibition by acceptors, but at the same time was itself inhibitory. All three acceptors competed with one another for galactose incorporation, indicating that a single enzyme catalyzed the transfer of galactose for all acceptors."}
{"id": "PMID:14166", "title": "The pH and temperature dependence of the interaction of steroid hormones with the transport system of glucose in human erythrocytes.", "content": "The thermodynamic parameters deltaH degrees, deltaF degrees, deltaS degrees and the pH dependence of the interaction between steroids and the glucose carrier in human erythrocytes have been studied. The results indicate that, according to the structure of the steroids, hydrophilic as well as hydrophobic bonds can be involved in the association. For the binding of the C-21-steroids to the carrier the polarity rule has been observed to be valid. On the basis of the thermodynamic parameters it has been found that in the association process of the steroids with the carrier, simultaneous randomization of ordered water molecules is important.", "contents": "The pH and temperature dependence of the interaction of steroid hormones with the transport system of glucose in human erythrocytes. The thermodynamic parameters deltaH degrees, deltaF degrees, deltaS degrees and the pH dependence of the interaction between steroids and the glucose carrier in human erythrocytes have been studied. The results indicate that, according to the structure of the steroids, hydrophilic as well as hydrophobic bonds can be involved in the association. For the binding of the C-21-steroids to the carrier the polarity rule has been observed to be valid. On the basis of the thermodynamic parameters it has been found that in the association process of the steroids with the carrier, simultaneous randomization of ordered water molecules is important."}
{"id": "PMID:14167", "title": "The in vivo effect of dimethyl sulphoxide (DMSO) on protein synthesis and the polyribosome profile in Paramecium.", "content": "When Paramecium tetraurelia in log phase growth is treated with 4% dimethyl sulphoxide (DMSO) for five minutes the amount of polyribosomes is reduced 3- to 4-fold while there is a corresponding increase in 80s ribosomal material. Reducing the concentration of DMSO to 1% allows immediate reversal of the condition. Paramecium polyribosomes subjected to 4% DMSO either in whole cell homogenates or during purification through sucrose density gradients appear unaffected while cycloheximide at concentrations up to 100 mug/ml did not prevent DMSO from exerting its effect in vivo. Analyses of 14C amino acid incorporation experiments indicated a strict correspondence between the effect of DMSO on polyribosomes and overall protein synthesis. The reduction of acid precipitable radioactivity in the polyribosomal region after DMSO treatment was associated with a corresponding increase in radioactivity in the 80s region. There was no comparable increase in the acid precipitable radioactivity in the soluble fraction. The overall results of the study suggest that DMSO acts on polyribosommes indirectly through some unknown primary reaction with cell constitutents, and that the mode of action is such as to cause the release of ribosomes from messenger RNA (mRNA) rather than to prevent initiation of the ribosome-mRNA complex. Our data suggest that the effect may be selective. Finally, it is of interest that high concentrations of DMSO (above 8%) appear to have the opposite effect of lower concentrations of DMSO, i.e., they appear to \"freeze\" the ribosomes to mRNA.", "contents": "The in vivo effect of dimethyl sulphoxide (DMSO) on protein synthesis and the polyribosome profile in Paramecium. When Paramecium tetraurelia in log phase growth is treated with 4% dimethyl sulphoxide (DMSO) for five minutes the amount of polyribosomes is reduced 3- to 4-fold while there is a corresponding increase in 80s ribosomal material. Reducing the concentration of DMSO to 1% allows immediate reversal of the condition. Paramecium polyribosomes subjected to 4% DMSO either in whole cell homogenates or during purification through sucrose density gradients appear unaffected while cycloheximide at concentrations up to 100 mug/ml did not prevent DMSO from exerting its effect in vivo. Analyses of 14C amino acid incorporation experiments indicated a strict correspondence between the effect of DMSO on polyribosomes and overall protein synthesis. The reduction of acid precipitable radioactivity in the polyribosomal region after DMSO treatment was associated with a corresponding increase in radioactivity in the 80s region. There was no comparable increase in the acid precipitable radioactivity in the soluble fraction. The overall results of the study suggest that DMSO acts on polyribosommes indirectly through some unknown primary reaction with cell constitutents, and that the mode of action is such as to cause the release of ribosomes from messenger RNA (mRNA) rather than to prevent initiation of the ribosome-mRNA complex. Our data suggest that the effect may be selective. Finally, it is of interest that high concentrations of DMSO (above 8%) appear to have the opposite effect of lower concentrations of DMSO, i.e., they appear to \"freeze\" the ribosomes to mRNA."}
{"id": "PMID:14168", "title": "Enzyme inactivation by a cellular neutral protease: enzyme specificity, effects of ligands on inactivation, and implications for the regulation of enzyme degradation.", "content": "A protease from Tetrahymena pyriformis inactivated eight of nine commercially available enzymes tested, including lactate deyhdrogenase, isocitrate dehydrogenase (TPN-specific), glucose-6 phosphate dehydrogenase, D-amino acid oxidase, fumarase, pyruvate kinase, hexokinase, and citrate synthase. Urate oxidase was not inactivated. Inactivation occurred at neutral pH, was prevented by inhibitors of the protease, and followed first order kinetics. In those cases tested, inactivation was enhanced by mercaptoethanol. Most of the enzyme-inactivating activity was due to a protease of molecular weight 25,000 that eluted from DEAE-Sephadex at 0.3 M KCl. A second protease of this molecular weight, which was not retained by the gel, inactivated only isocitrate dehydrogenase and D-amino acid oxidase. These two proteases could also be distinguished by temperature and inhibitor sensitivity. Two other protease peaks obtained by DEAE-Sephadex chromatography had little or no no enzyme inactivating activity, while another attacked only D-amino acid oxidase. At least six of the enzymes could be protected from proteolytic inactivation by various ligands. Isocitrates dehydrogenase was protected by isocitrate, TPN, or TPNH, glucose-6-dehydrogenase by glucose-6-P or TPN, pyruvate kinase by phosphoenolypyruvate or ADP, hexokinase by glucose, and fumarase by a mixture of fumarate and malate. Lactate dehdrogenase was not protected by either of its substrates of coenzymes. Citrate synthase was probably protected by oxalacetate. Our data suggest that the protease or proteases discussed here may participate in the inactivation or degradation of a least some enzymes in Tetrahymena. Since the inactivation occurs at neutral pH, this process could be regulated by variations in the cellular levels of substrates, coenzymes, or allosteric regulators resulting form changes in growth conditions or growth state. Such a mechanism would permit the selective retention of enzymes of metabolically active pathways.", "contents": "Enzyme inactivation by a cellular neutral protease: enzyme specificity, effects of ligands on inactivation, and implications for the regulation of enzyme degradation. A protease from Tetrahymena pyriformis inactivated eight of nine commercially available enzymes tested, including lactate deyhdrogenase, isocitrate dehydrogenase (TPN-specific), glucose-6 phosphate dehydrogenase, D-amino acid oxidase, fumarase, pyruvate kinase, hexokinase, and citrate synthase. Urate oxidase was not inactivated. Inactivation occurred at neutral pH, was prevented by inhibitors of the protease, and followed first order kinetics. In those cases tested, inactivation was enhanced by mercaptoethanol. Most of the enzyme-inactivating activity was due to a protease of molecular weight 25,000 that eluted from DEAE-Sephadex at 0.3 M KCl. A second protease of this molecular weight, which was not retained by the gel, inactivated only isocitrate dehydrogenase and D-amino acid oxidase. These two proteases could also be distinguished by temperature and inhibitor sensitivity. Two other protease peaks obtained by DEAE-Sephadex chromatography had little or no no enzyme inactivating activity, while another attacked only D-amino acid oxidase. At least six of the enzymes could be protected from proteolytic inactivation by various ligands. Isocitrates dehydrogenase was protected by isocitrate, TPN, or TPNH, glucose-6-dehydrogenase by glucose-6-P or TPN, pyruvate kinase by phosphoenolypyruvate or ADP, hexokinase by glucose, and fumarase by a mixture of fumarate and malate. Lactate dehdrogenase was not protected by either of its substrates of coenzymes. Citrate synthase was probably protected by oxalacetate. Our data suggest that the protease or proteases discussed here may participate in the inactivation or degradation of a least some enzymes in Tetrahymena. Since the inactivation occurs at neutral pH, this process could be regulated by variations in the cellular levels of substrates, coenzymes, or allosteric regulators resulting form changes in growth conditions or growth state. Such a mechanism would permit the selective retention of enzymes of metabolically active pathways."}
{"id": "PMID:14169", "title": "Quantitative gas chromatographic analysis of flunitrazepam in human serum with electron-capture detection.", "content": "A rapid method for the determination of flunitrazepam and desmethylfflunitrazepam in human serum in the range 10-300 ng/ml is described. Both drugs are isolated from biological material by means of a single extraction, part of the organic phase is evaporated to dryness and the residue is dissolved in a small volume of benzene. Without further purification, the substance is determined gas chromatographically with an electron-capture detector configuration of 63Ni-type. The method permits the quantitative determination of at least 25-300 ng/ml with an overall recovery of flunitrazepam of 99.7 +/- 4.9% and of desmethylflunitrazepam of 98.6 +/- 7.8% from serum. All calculations were carried out by a data system that was programmed for this purpose. The limit of detection for flunitrazepam is of the order of 1 ng/ml in serum. The method is sufficiently sensitive and specific for therapy control purposes. The time needed for an analysis is less than 1 h.", "contents": "Quantitative gas chromatographic analysis of flunitrazepam in human serum with electron-capture detection. A rapid method for the determination of flunitrazepam and desmethylfflunitrazepam in human serum in the range 10-300 ng/ml is described. Both drugs are isolated from biological material by means of a single extraction, part of the organic phase is evaporated to dryness and the residue is dissolved in a small volume of benzene. Without further purification, the substance is determined gas chromatographically with an electron-capture detector configuration of 63Ni-type. The method permits the quantitative determination of at least 25-300 ng/ml with an overall recovery of flunitrazepam of 99.7 +/- 4.9% and of desmethylflunitrazepam of 98.6 +/- 7.8% from serum. All calculations were carried out by a data system that was programmed for this purpose. The limit of detection for flunitrazepam is of the order of 1 ng/ml in serum. The method is sufficiently sensitive and specific for therapy control purposes. The time needed for an analysis is less than 1 h."}
{"id": "PMID:14171", "title": "Mass fragmentographic quantitation of ethotoin and some of its metabolites in human urine.", "content": "A method for the determination of ethotoin and its p-hydroxylated and dealkylated metabolites in urine has been developed. Ethotoin and the metabolites were extracted from acidified urine with ethyl acetate and silylated before injection into a combined gas chromatograph--mass spectrometer. Four partly identified metabolites were recorded, but their exact quantitation was not possible as pure reference substances were not available. The limit of sensitivity was far below the amounts of ethotoin and of its metabolites found in urine from patients treated with therapeutic doses of ethotoin.", "contents": "Mass fragmentographic quantitation of ethotoin and some of its metabolites in human urine. A method for the determination of ethotoin and its p-hydroxylated and dealkylated metabolites in urine has been developed. Ethotoin and the metabolites were extracted from acidified urine with ethyl acetate and silylated before injection into a combined gas chromatograph--mass spectrometer. Four partly identified metabolites were recorded, but their exact quantitation was not possible as pure reference substances were not available. The limit of sensitivity was far below the amounts of ethotoin and of its metabolites found in urine from patients treated with therapeutic doses of ethotoin."}
{"id": "PMID:14172", "title": "Evidence for the existence of a large molecular weight protein in human pituitary tissue having follicle stimulating hormone activity.", "content": "A large molecular weight protein fraction was isolated during purification of follicle stimulating hormone (hFSH) from acetone preserved human pituitary glands. This large molecular weight fraction, F-1, was not retarded by Sephadex G-100 as was hFSH, nor did it penetrate 7.5% acrylamide gel upon electrophoresis in sodium dodecyl sulfate as did hFSH. There was no evidence of dissociation of F-1 into smaller molecular weight fractions upon its refiltration through Sephadex G-100 or upon electrophoresis, suggesting F-1 was not an aggregate of smaller size proteins. Fraction F-1 stimulated ovarian growth in rats, inhibited binding of 125I-hFSH to rat testes membranes and cross-reacted with antiserum to hFSH, hFSH-alpha subunit and hFSH-beta subunit as determined by radioimmunoassay. Based on gel filtration experiments, it seemed unlikely that immunologic activity against subunit antisera could be attributed to contamination of F-1 by free FSH subunits. The membrane binding activity of F-1 decreased after incubation with 8M urea, but at a rate less than 1/2 that seen with intact hFSH similarly treated, indicating the two activities were not identical. These results suggest that human pituitary tissue contains a large molecular weight protein with FSH-like biologic and immunologic activity, but which is distinct from native hFSH.", "contents": "Evidence for the existence of a large molecular weight protein in human pituitary tissue having follicle stimulating hormone activity. A large molecular weight protein fraction was isolated during purification of follicle stimulating hormone (hFSH) from acetone preserved human pituitary glands. This large molecular weight fraction, F-1, was not retarded by Sephadex G-100 as was hFSH, nor did it penetrate 7.5% acrylamide gel upon electrophoresis in sodium dodecyl sulfate as did hFSH. There was no evidence of dissociation of F-1 into smaller molecular weight fractions upon its refiltration through Sephadex G-100 or upon electrophoresis, suggesting F-1 was not an aggregate of smaller size proteins. Fraction F-1 stimulated ovarian growth in rats, inhibited binding of 125I-hFSH to rat testes membranes and cross-reacted with antiserum to hFSH, hFSH-alpha subunit and hFSH-beta subunit as determined by radioimmunoassay. Based on gel filtration experiments, it seemed unlikely that immunologic activity against subunit antisera could be attributed to contamination of F-1 by free FSH subunits. The membrane binding activity of F-1 decreased after incubation with 8M urea, but at a rate less than 1/2 that seen with intact hFSH similarly treated, indicating the two activities were not identical. These results suggest that human pituitary tissue contains a large molecular weight protein with FSH-like biologic and immunologic activity, but which is distinct from native hFSH."}
{"id": "PMID:14173", "title": "Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate.", "content": "Since monosodium urate (NaU) may play an important etiologic role in the formation of renal stones containing Ca in patients with hyperuricosuria, the current studies were undertaken to define some of the physiocochemical factors which determine the formation of NaU. In solutions containing Na, uric acid was rapidly transformed to NaU at pH greater than 6. The results indicated that NaU, and not uric acid, was the stable phase above this pH. A reliable and simple method for the calculation of the state of saturation of urine with respect to NaU was developed from the ratio of concentration products of Na and total dissolved urate (Upi) in the ambient fluid before and after incubation of urine with synthetic NaU. The concentration product ratio closely approximated the ratio of activity products of Na+ and acid urate ion. In contrast, the relative saturation ratio, or the ratio of activity product of original sample and the thermodynamic solubility product of NaU, often differed from the activity product ratio in the individual urine samples. With the concentration product rate, it was found in 45 urine samples that a critical determinant for the supersaturated state with respect to NaU was the high concentration of UT. At UT greater than 300 mg/liter, urine samples were invariably supersaturated with respect to NaU. These results suggest that the nidus of NaU could potentially form in the urine of patients with hyperuricosuria and Ca stones.", "contents": "Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate. Since monosodium urate (NaU) may play an important etiologic role in the formation of renal stones containing Ca in patients with hyperuricosuria, the current studies were undertaken to define some of the physiocochemical factors which determine the formation of NaU. In solutions containing Na, uric acid was rapidly transformed to NaU at pH greater than 6. The results indicated that NaU, and not uric acid, was the stable phase above this pH. A reliable and simple method for the calculation of the state of saturation of urine with respect to NaU was developed from the ratio of concentration products of Na and total dissolved urate (Upi) in the ambient fluid before and after incubation of urine with synthetic NaU. The concentration product ratio closely approximated the ratio of activity products of Na+ and acid urate ion. In contrast, the relative saturation ratio, or the ratio of activity product of original sample and the thermodynamic solubility product of NaU, often differed from the activity product ratio in the individual urine samples. With the concentration product rate, it was found in 45 urine samples that a critical determinant for the supersaturated state with respect to NaU was the high concentration of UT. At UT greater than 300 mg/liter, urine samples were invariably supersaturated with respect to NaU. These results suggest that the nidus of NaU could potentially form in the urine of patients with hyperuricosuria and Ca stones."}
{"id": "PMID:14174", "title": "Fluorescence polarization studies of rat intestinal microvillus membranes.", "content": "Rat intestinal microvillus membranes and lipid extracts prepared from them have been studied by fluorescence polarization with three lipid-soluble fluorophores: diphenylhexatriene, retinol, and anthroyl-stearate. The degree of fluorescence polarization of diphenylhexatriene, which provides an index of the \"microviscosity\" of the lipid regions of the membrane, is exceptionally high in microvillus membranes, the highest yet reported in normal biological membranes. Both the membrane proteins and lipids were found to contribute to the high values. With each of the three probes the polarization values are higher in ileal microvillus membranes as compared to membranes from proximal intestinal segments. Temperature-dependence studies of the fluorescence polarization of diphenylhexatriene and anthroylstearate demonstrate a phase transition in microvillus membranes and in liposomes prepared from their lipid extracts at approximately 26+/-2 degrees C. Ambient pH influences markedly the diphenylhexatriene fluorescence polarization in microvillus membranes but has little effect on that of human erythrocyte ghost membranes. The \"microviscosity\" of jejunal microvillus membranes is maximal at pH 6.5-7.0 and decreases as much as 50% at pH 3.0, an effect which depends largely upon the membrane proteins. Addition of calcium ions to suspensions of microvillus membranes increases the fluorescence polarization of retinol and anthroyl-stearate, but not that of diphenyl-hexatriene. This confirms the localization of the last compound to the hydrophobic interior of the membrane, relatively distant from the hydrophilic head groups of the polar lipids. Microvillus membrane proteins solubilized with Triton X-100 give relatively high fluorescence polarization and intensity values with retinol, suggesting the presence of binding proteins which could play a role in the normal absorptive mechanism for the vitamin.", "contents": "Fluorescence polarization studies of rat intestinal microvillus membranes. Rat intestinal microvillus membranes and lipid extracts prepared from them have been studied by fluorescence polarization with three lipid-soluble fluorophores: diphenylhexatriene, retinol, and anthroyl-stearate. The degree of fluorescence polarization of diphenylhexatriene, which provides an index of the \"microviscosity\" of the lipid regions of the membrane, is exceptionally high in microvillus membranes, the highest yet reported in normal biological membranes. Both the membrane proteins and lipids were found to contribute to the high values. With each of the three probes the polarization values are higher in ileal microvillus membranes as compared to membranes from proximal intestinal segments. Temperature-dependence studies of the fluorescence polarization of diphenylhexatriene and anthroylstearate demonstrate a phase transition in microvillus membranes and in liposomes prepared from their lipid extracts at approximately 26+/-2 degrees C. Ambient pH influences markedly the diphenylhexatriene fluorescence polarization in microvillus membranes but has little effect on that of human erythrocyte ghost membranes. The \"microviscosity\" of jejunal microvillus membranes is maximal at pH 6.5-7.0 and decreases as much as 50% at pH 3.0, an effect which depends largely upon the membrane proteins. Addition of calcium ions to suspensions of microvillus membranes increases the fluorescence polarization of retinol and anthroyl-stearate, but not that of diphenyl-hexatriene. This confirms the localization of the last compound to the hydrophobic interior of the membrane, relatively distant from the hydrophilic head groups of the polar lipids. Microvillus membrane proteins solubilized with Triton X-100 give relatively high fluorescence polarization and intensity values with retinol, suggesting the presence of binding proteins which could play a role in the normal absorptive mechanism for the vitamin."}
{"id": "PMID:14176", "title": "Seminal quality, spermatozoal outpost, and testicular changes in growing Holstein bulls.", "content": "Nine Holstein bulls, initially between the ages of 17 and 22 mo, awaiting proofs in artificial breeding, were ejaculated each summer for 3 yr, and 8 and 7 survivors for 4 and 5 yr, respectively, to study changes in the same group of bulls and determine the predictive value of early measurements. Semen was collected twice a day, 2 days per wk, for 4 wk. Bulls differed in testicular size, consistency, ejaculate volume, total spermatozoal output, percentage of unstained spermatozoa and abnormal spermatozoa, and in several storage and freezing tests. The largest yearly effects were on testis size and consistency, ejaculate volume, and total output of spermatozoa. The latter increased per bull from 28.3 X 10(9) per wk at 17 to 22 mo of age to 40.9 X 10(9) per wk 4 yr later, representing a high output of spermatozoa with a total of only 20 min of intensive sexual preparation per wk. The correlation between testis size and spermatozoal output was .72. Testicular consistency was indicative of semen quality measured simultaneously as judged by correlations with spermatozoal characteristics ranging from .61 to .95. These characteristics are believed to be representative of those Holstein bulls in artificial breeding which are ejaculated frequently.", "contents": "Seminal quality, spermatozoal outpost, and testicular changes in growing Holstein bulls. Nine Holstein bulls, initially between the ages of 17 and 22 mo, awaiting proofs in artificial breeding, were ejaculated each summer for 3 yr, and 8 and 7 survivors for 4 and 5 yr, respectively, to study changes in the same group of bulls and determine the predictive value of early measurements. Semen was collected twice a day, 2 days per wk, for 4 wk. Bulls differed in testicular size, consistency, ejaculate volume, total spermatozoal output, percentage of unstained spermatozoa and abnormal spermatozoa, and in several storage and freezing tests. The largest yearly effects were on testis size and consistency, ejaculate volume, and total output of spermatozoa. The latter increased per bull from 28.3 X 10(9) per wk at 17 to 22 mo of age to 40.9 X 10(9) per wk 4 yr later, representing a high output of spermatozoa with a total of only 20 min of intensive sexual preparation per wk. The correlation between testis size and spermatozoal output was .72. Testicular consistency was indicative of semen quality measured simultaneously as judged by correlations with spermatozoal characteristics ranging from .61 to .95. These characteristics are believed to be representative of those Holstein bulls in artificial breeding which are ejaculated frequently."}
{"id": "PMID:14177", "title": "Extracellular dextran hydrolase from Streptococcus mutans strain 6715.", "content": "Streptococcus mutans strain 6715 was shown to produce an extracellular dextramase with endohydrolytic alpha-(1 leads to 6)-glucan-6-glucanohydrolase activity. The enzyme degraded soluble polymers produced by some oral streptococci but did not disperse the streptococcal plaques tested. Enzyme levels in the culture supernatant were elevated in sucrose and sucrose plus glucose cultures but remained at basal levels in glucose and dextran plus glucose cultures.", "contents": "Extracellular dextran hydrolase from Streptococcus mutans strain 6715. Streptococcus mutans strain 6715 was shown to produce an extracellular dextramase with endohydrolytic alpha-(1 leads to 6)-glucan-6-glucanohydrolase activity. The enzyme degraded soluble polymers produced by some oral streptococci but did not disperse the streptococcal plaques tested. Enzyme levels in the culture supernatant were elevated in sucrose and sucrose plus glucose cultures but remained at basal levels in glucose and dextran plus glucose cultures."}
{"id": "PMID:14178", "title": "Compratative distortion in three-unit fixed prostheses joined by laser welding, conventioanl soldering, or casting in one piece.", "content": "This study evaluated three different joint-forming procedures: laser welding, soldering, and one-piece casting. Fifteen three-unit bridges were fabricated. The findings showed post-jointing distrotion to be significantly less for laser-welded and one-piece  castings than for soldering; and significantly greater reliability (least error variance) in joining with the laser than either one-piece casting or  soldering.", "contents": "Compratative distortion in three-unit fixed prostheses joined by laser welding, conventioanl soldering, or casting in one piece. This study evaluated three different joint-forming procedures: laser welding, soldering, and one-piece casting. Fifteen three-unit bridges were fabricated. The findings showed post-jointing distrotion to be significantly less for laser-welded and one-piece  castings than for soldering; and significantly greater reliability (least error variance) in joining with the laser than either one-piece casting or  soldering."}
{"id": "PMID:14175", "title": "Reduction of adenylate cyclase activity in lysates of human platelets by the alpha-adrenergic component of epinephrine.", "content": "The effects of the alpha- and beta-adrenergic components of epinephrine on adenylate cyclase activity were studied in lyastes of human platelets. The beta-adrenergic component increased enzyme activity between 20 and 50%, whereas the alpha-adrenergic component caused a concentration-dependent reduction of adenylate cyclase activity. The maximal inhibition of adenylate cyclase was 50 to 60% with about 100 muM epinephrine; about 1 muM epinephrine caused half-maximal inhibition. The alpha-adrenergic reduction of adenylate cyclase activity appeared to be immediate and was specific for platelets from species in which alpha-adrenergic stimulation caused aggregation. Adenylate cyclase activity measured in the presence of prostaglandins of fluoride was also reduced by the alpha-adrenergic component of epinephrine, but the inhibitory effect was less than on basal activity. In contrast, the 5'-guanylylimidodiphosphate-stimulated enzyme was not affected by stimulation of alpha-adrenergic receptors.", "contents": "Reduction of adenylate cyclase activity in lysates of human platelets by the alpha-adrenergic component of epinephrine. The effects of the alpha- and beta-adrenergic components of epinephrine on adenylate cyclase activity were studied in lyastes of human platelets. The beta-adrenergic component increased enzyme activity between 20 and 50%, whereas the alpha-adrenergic component caused a concentration-dependent reduction of adenylate cyclase activity. The maximal inhibition of adenylate cyclase was 50 to 60% with about 100 muM epinephrine; about 1 muM epinephrine caused half-maximal inhibition. The alpha-adrenergic reduction of adenylate cyclase activity appeared to be immediate and was specific for platelets from species in which alpha-adrenergic stimulation caused aggregation. Adenylate cyclase activity measured in the presence of prostaglandins of fluoride was also reduced by the alpha-adrenergic component of epinephrine, but the inhibitory effect was less than on basal activity. In contrast, the 5'-guanylylimidodiphosphate-stimulated enzyme was not affected by stimulation of alpha-adrenergic receptors."}
{"id": "PMID:14209", "title": "The distribution of acid and alkaline ribonuclease activities in preneoplastic and neoplastic rat livers.", "content": "Ribonuclease (RNase) activities revealed by the substrate film method were compared with reactions for acid and alkaline RNase obtained by lead precipitation technique in serial sections of preneoplastic livers and hepatomas. The preneoplastic parenchymal tissue giving positive reactions with ribonucleic acid films showed both acid and alkaline RNase activities by lead precipitation technique, and the area of hyperplastic nodules nonreactive against substrate films were deficient in acid and alkaline RNase activities. Preneoplastic hyperbasophilic foci and hepatoma gave weak or negative reactions by either method, but necrotic areas and stromal tissue showed appreciable RNase activities. Thus a good correlation was observed in these tissues between the RNase activities revealed by the film method and those demonstrated by lead precipitation.", "contents": "The distribution of acid and alkaline ribonuclease activities in preneoplastic and neoplastic rat livers. Ribonuclease (RNase) activities revealed by the substrate film method were compared with reactions for acid and alkaline RNase obtained by lead precipitation technique in serial sections of preneoplastic livers and hepatomas. The preneoplastic parenchymal tissue giving positive reactions with ribonucleic acid films showed both acid and alkaline RNase activities by lead precipitation technique, and the area of hyperplastic nodules nonreactive against substrate films were deficient in acid and alkaline RNase activities. Preneoplastic hyperbasophilic foci and hepatoma gave weak or negative reactions by either method, but necrotic areas and stromal tissue showed appreciable RNase activities. Thus a good correlation was observed in these tissues between the RNase activities revealed by the film method and those demonstrated by lead precipitation."}
{"id": "PMID:14210", "title": "Surface localization of 5'-nucleotidase on the mouse lymphocyte.", "content": "The optimal conditions for the cytochemical localization of 5'-nucleotidase (AMPase) in the mouse lymphocyte have been established. Quantitative monitoring of the effects of fixation and the components of the cytochemical medium showed that the cytochemistry can be performed under conditions that do not lead to loss of AMPase activity, and also under conditions where penetration of the substrate into the cell has occurred. The cytochemical reaction product was seen only on the surface of a proportion of splenic lymphocytes, regardless of the fixative used. Biochemical data confirmed that AMPase is an ectoenzyme and is the only protein in splenic lymphocytes capable of catalysing the hydrolysis of AMP. The activity of 5'-nucleotidase was studied also by harvesting cells either from thymus or spleen of A/ST or Cd-1 mouse strains. The enzymatic activity in splenic lymphocytes was more than six time higher than the activity of intact thymus cells. Cytochemically it was evident that within splenic lymphocytes there was a distinct population of lymphocytes with readily demonstrable AMPase activity, and another with no cytochemically demonstrable AMPase activity. It was concluded that murine lymphocytes vary in their activity of AMPase, and that the enzyme is exclusively confined to the cell surface.", "contents": "Surface localization of 5'-nucleotidase on the mouse lymphocyte. The optimal conditions for the cytochemical localization of 5'-nucleotidase (AMPase) in the mouse lymphocyte have been established. Quantitative monitoring of the effects of fixation and the components of the cytochemical medium showed that the cytochemistry can be performed under conditions that do not lead to loss of AMPase activity, and also under conditions where penetration of the substrate into the cell has occurred. The cytochemical reaction product was seen only on the surface of a proportion of splenic lymphocytes, regardless of the fixative used. Biochemical data confirmed that AMPase is an ectoenzyme and is the only protein in splenic lymphocytes capable of catalysing the hydrolysis of AMP. The activity of 5'-nucleotidase was studied also by harvesting cells either from thymus or spleen of A/ST or Cd-1 mouse strains. The enzymatic activity in splenic lymphocytes was more than six time higher than the activity of intact thymus cells. Cytochemically it was evident that within splenic lymphocytes there was a distinct population of lymphocytes with readily demonstrable AMPase activity, and another with no cytochemically demonstrable AMPase activity. It was concluded that murine lymphocytes vary in their activity of AMPase, and that the enzyme is exclusively confined to the cell surface."}
{"id": "PMID:14211", "title": "Activation of the alternative pathway by pneumococcal cell walls.", "content": "The present studies were performed in order to identify the pneumococcal subcellular component responsible for activating the alternative pathway. Purified pneumococcal cell walls were able to activate the alternative pathway at a concentration as low as 5 mug/ml and were more active than crude cell walls, which in turn were more active than the whole organism. Purified pneumococcal cell membranes also were able to activiate the alternative pathway but had less than 10% of the activity of the purified walls. Thus, the cell wall appears to play a major role in pneumococcal activation of the alternative pathway. Pneumococcal cell walls containing ethanolamine were as effective as cell walls containing choline in activating the alternative pathway. Since C-reactive protein binds specifically to the phosphorylcholine residue of pneumococcal C-polysaccharide, it is unlikely that pneumococcal cell walls must combine with C-reactive protein in order to activate the alternative pathway.", "contents": "Activation of the alternative pathway by pneumococcal cell walls. The present studies were performed in order to identify the pneumococcal subcellular component responsible for activating the alternative pathway. Purified pneumococcal cell walls were able to activate the alternative pathway at a concentration as low as 5 mug/ml and were more active than crude cell walls, which in turn were more active than the whole organism. Purified pneumococcal cell membranes also were able to activiate the alternative pathway but had less than 10% of the activity of the purified walls. Thus, the cell wall appears to play a major role in pneumococcal activation of the alternative pathway. Pneumococcal cell walls containing ethanolamine were as effective as cell walls containing choline in activating the alternative pathway. Since C-reactive protein binds specifically to the phosphorylcholine residue of pneumococcal C-polysaccharide, it is unlikely that pneumococcal cell walls must combine with C-reactive protein in order to activate the alternative pathway."}
{"id": "PMID:14212", "title": "Differential effects of alloimmunization on T cells mediating graft-vs-host splenomegaly or the allogeneic effect in F1 mice.", "content": "Spleen cells from normal BALB/c mice or mice immunized 10 or 30 days previously with C57BL/6 spleen cells were tested for a) their capacity to produce graft-vs-host (GVH) reactions in newborn F1 mice and b) their capacity to produce an allogeneic effect in adult F1 mice immunized with Type III pneumococcal polysaccharide. GVH reactivity of alloimmune spleen cells obtained 10 or 30 days after immunization was significantly increased as compared to the reactivity of normal spleen cells in that a) at comparable cell doses, higher spleen indices were obtained with alloimmune cells than normal cells, and b) alloimmune cells produced severe runting at lower cell doses than normal cells. By comparison, the capacity of alloimmune spleen cells to produce an allogeneic effect was reduced 50% on a per cell basis as compared to normal spleen cells at both 10 and 30 days after immunization. These results give further evidence that T cells producing the allogeneic effect are distinct from the T cell populations which interact to produce GVH splenomegaly.", "contents": "Differential effects of alloimmunization on T cells mediating graft-vs-host splenomegaly or the allogeneic effect in F1 mice. Spleen cells from normal BALB/c mice or mice immunized 10 or 30 days previously with C57BL/6 spleen cells were tested for a) their capacity to produce graft-vs-host (GVH) reactions in newborn F1 mice and b) their capacity to produce an allogeneic effect in adult F1 mice immunized with Type III pneumococcal polysaccharide. GVH reactivity of alloimmune spleen cells obtained 10 or 30 days after immunization was significantly increased as compared to the reactivity of normal spleen cells in that a) at comparable cell doses, higher spleen indices were obtained with alloimmune cells than normal cells, and b) alloimmune cells produced severe runting at lower cell doses than normal cells. By comparison, the capacity of alloimmune spleen cells to produce an allogeneic effect was reduced 50% on a per cell basis as compared to normal spleen cells at both 10 and 30 days after immunization. These results give further evidence that T cells producing the allogeneic effect are distinct from the T cell populations which interact to produce GVH splenomegaly."}
{"id": "PMID:14213", "title": "Suppressor T cells arising in mice undergoing a graft-vs-host response.", "content": "We investigated the ability of mice to generate antibody-forming cells when undergoing a graft-vs-host reaction. (C57BL/6 X DBA/2)F1 mice (BDF1) injected with C57BL/6 spleen cells generated suppressor T cells which inhibit antibody synthesis by BDF1 spleen cells in vitro. These T cells arose from the donor inoculum. They differ from helper T cells in size and they act directly on antigen reactive B cells. The suppressor T cells were specifically directed against components of the H-2 region of the reciprocal parental strain (DBA/2 = H-2d) in the hybrid F1 mouse.", "contents": "Suppressor T cells arising in mice undergoing a graft-vs-host response. We investigated the ability of mice to generate antibody-forming cells when undergoing a graft-vs-host reaction. (C57BL/6 X DBA/2)F1 mice (BDF1) injected with C57BL/6 spleen cells generated suppressor T cells which inhibit antibody synthesis by BDF1 spleen cells in vitro. These T cells arose from the donor inoculum. They differ from helper T cells in size and they act directly on antigen reactive B cells. The suppressor T cells were specifically directed against components of the H-2 region of the reciprocal parental strain (DBA/2 = H-2d) in the hybrid F1 mouse."}
{"id": "PMID:14214", "title": "Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras.", "content": "The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production.", "contents": "Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras. The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production."}
{"id": "PMID:14215", "title": "In vitro inhibition of collagen cross links by catechol analogs.", "content": "Catechol analogs inhibit the formation of hydroxylysine-derived intermolecular collagen cross links in tissue cultures of chick embryo calvaria. Formation of intermolecular collagen cross links was measured following incorporation of [14C]lysine, reduction with sodium borohydride, and elution from an ion exchange column with a pyridine-formate gradient. Cultures grown in the presence of 10(-3) M catechol, 10(-3) M dopamine, 10(-3) M L-dopa, or 10(-3) M D,L-serine-(2,3,4-trihydroxybenzyl)-hydrazide demonstrated between 43 and 84% inhibition of hydroxylysine formation. Collagen biosynthesis was not diminished in these cultures as compared to controls without additions or with beta-aminopropionitrile when measured by collagenase digestion. The formation of hydroxylysine-derived intermolecular cross links was inhibited 34 to 93% for 5,5'-dihydroxylysinonorleucine and 7 to 71% for 5-hydroxylysinonorleucine. The catechol analogs also inhibit the activity of lysyl hydroxylase as measured by specific tritium release as triated water from an L-[4,5-3H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Since catechol analogs inhibit the formation of hydroxylysine in a cell-free assay, these compounds must pass into the cells of calvaria in this culture system to inhibit intracellular hydroxylysine formation and subsequently to diminish the reducible intermolecular cross links of the newly synthesized collagen.", "contents": "In vitro inhibition of collagen cross links by catechol analogs. Catechol analogs inhibit the formation of hydroxylysine-derived intermolecular collagen cross links in tissue cultures of chick embryo calvaria. Formation of intermolecular collagen cross links was measured following incorporation of [14C]lysine, reduction with sodium borohydride, and elution from an ion exchange column with a pyridine-formate gradient. Cultures grown in the presence of 10(-3) M catechol, 10(-3) M dopamine, 10(-3) M L-dopa, or 10(-3) M D,L-serine-(2,3,4-trihydroxybenzyl)-hydrazide demonstrated between 43 and 84% inhibition of hydroxylysine formation. Collagen biosynthesis was not diminished in these cultures as compared to controls without additions or with beta-aminopropionitrile when measured by collagenase digestion. The formation of hydroxylysine-derived intermolecular cross links was inhibited 34 to 93% for 5,5'-dihydroxylysinonorleucine and 7 to 71% for 5-hydroxylysinonorleucine. The catechol analogs also inhibit the activity of lysyl hydroxylase as measured by specific tritium release as triated water from an L-[4,5-3H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Since catechol analogs inhibit the formation of hydroxylysine in a cell-free assay, these compounds must pass into the cells of calvaria in this culture system to inhibit intracellular hydroxylysine formation and subsequently to diminish the reducible intermolecular cross links of the newly synthesized collagen."}
{"id": "PMID:14216", "title": "Photoreactions of 3,3',4',5-tetrachlorosalicylanilide with proteins.", "content": "The photoreactions of 3,3',4',5-tetrachlorosalicylanilide anion (TCSA-) with two serum proteins were studied. TCSA- and anions of two similar compounds, N-ethyl-3,5-dichlorosalicylamide and salicylanilide, bind noncovalently to human serum albumin (HSA) without irradiation in aqueous pH 7.4 buffered solutions. TCSA- noncovalently bound to HSA yields three types of photoproducts when irradiated with ultraviolet light (lambda greater than 360 nm). A covalently bonded photoadduct between TCSA- and HSA is formed and histidines in HSA are chemically modified. In addition to these two types of photoproducts which involve HSA, two of the four TCSA- photoproducts which form when HSA is absent are also formed when the TCSA-/HSA complex is irradiated. The results presented indicate that not all proteins in the skin are capable of being the carrier protein in photoallergy of TCSA- and that cross reactivity to other halogenated salicylanilides can be explained by further photochemical reactions of TCSA- photoproducts.", "contents": "Photoreactions of 3,3',4',5-tetrachlorosalicylanilide with proteins. The photoreactions of 3,3',4',5-tetrachlorosalicylanilide anion (TCSA-) with two serum proteins were studied. TCSA- and anions of two similar compounds, N-ethyl-3,5-dichlorosalicylamide and salicylanilide, bind noncovalently to human serum albumin (HSA) without irradiation in aqueous pH 7.4 buffered solutions. TCSA- noncovalently bound to HSA yields three types of photoproducts when irradiated with ultraviolet light (lambda greater than 360 nm). A covalently bonded photoadduct between TCSA- and HSA is formed and histidines in HSA are chemically modified. In addition to these two types of photoproducts which involve HSA, two of the four TCSA- photoproducts which form when HSA is absent are also formed when the TCSA-/HSA complex is irradiated. The results presented indicate that not all proteins in the skin are capable of being the carrier protein in photoallergy of TCSA- and that cross reactivity to other halogenated salicylanilides can be explained by further photochemical reactions of TCSA- photoproducts."}
{"id": "PMID:14218", "title": "Prolonged maintenance of 2,3-DPG in liquid blood storage: use of an internal CO2 trap to stabilize pH.", "content": "A close relationship exists between the decrease in concentration of 2,3-diphosphoglycerate (2,3-DPG) and a fall in the pH of stored blood. Buffering the stored red cells with bicarbonate is one solution to the problem of maintaining pH during storage. The effectiveness of this buffer depends upon loss from the stored blood of carbonic acid in the form of CO2. We describe a system in which the CO2 is trapped in a small internal package which contains calcium hydroxide, or calcium hydroxide embedded in Silastic. A medium containing bicarbonate, adenine, glucose, phosphate and mannitol (BAGPM) is added after initial packing of the erythrocytes. With this approach, it has been possible to maintain 2,3-DPG at 92 percent of original, and ATP was approximately 62 percent of initial levels at the end of 42 days of storage if an internal Silastic bag containing calcium was used in bags agitated once weekly. More frequent agitation (five times weekly) produced acceptable maintenance of both 2,3-DPG (78 percent of original) and ATP (44 percent of original) after 42 days of storage when a Silastic block impregnated with calcium hydroxide was utilized to absorb CO2.", "contents": "Prolonged maintenance of 2,3-DPG in liquid blood storage: use of an internal CO2 trap to stabilize pH. A close relationship exists between the decrease in concentration of 2,3-diphosphoglycerate (2,3-DPG) and a fall in the pH of stored blood. Buffering the stored red cells with bicarbonate is one solution to the problem of maintaining pH during storage. The effectiveness of this buffer depends upon loss from the stored blood of carbonic acid in the form of CO2. We describe a system in which the CO2 is trapped in a small internal package which contains calcium hydroxide, or calcium hydroxide embedded in Silastic. A medium containing bicarbonate, adenine, glucose, phosphate and mannitol (BAGPM) is added after initial packing of the erythrocytes. With this approach, it has been possible to maintain 2,3-DPG at 92 percent of original, and ATP was approximately 62 percent of initial levels at the end of 42 days of storage if an internal Silastic bag containing calcium was used in bags agitated once weekly. More frequent agitation (five times weekly) produced acceptable maintenance of both 2,3-DPG (78 percent of original) and ATP (44 percent of original) after 42 days of storage when a Silastic block impregnated with calcium hydroxide was utilized to absorb CO2."}
{"id": "PMID:14219", "title": "Delayed initiation of SS1 pulses in the sea anemone Calliactis parasitica: evidence for a fourth conducting system.", "content": "1. Single electrical shocks to the column sometimes elicit a series of 1-6 pulses in the SS1 (ectodermal slow system) but the first pulse does not appear until 5-28 s after stimulation. These pulses occur in addition to the early SS1 pulse which follows every shock and which has a conduction delay of less than 1 s. 2. The threshold of the delayed SS1 response is different from the thresholds of the three known conducting systems (through-conducting nerve net, SS1, and SS2). 3. In the case of stimulation of the column, the delayed SS1 pulses do not arise at the point of stimulation but probably originate in the tentacles or upper column. The pulse origin can shift during a single burst. 4. The pathway from the point of stimulation to the site of origin of delayed SS1 pulses is endodermal. We propose that this pathway represents a fourth conducting system (Delayed Initiation System--DIS). The DIS must connect, across the mesogloea, with the ectodermal SS1. The long pulse delay and repetitive firing may derive from pacemaker activity in the DIS. The DIS pacemakers closely resemble the pacemakers connected to the through-conducting nerve net. The DIS may be neuronal. 5. Delayed SS1 pulse bursts from unattached anemones showed an earlier onset, and more pulses/burst, than those from attached anemones. 6. Delayed SS1 pulses can also be evoked by electrical, and in some cases mechanical, stimulation of the pedal disc, tentacles, and pharynx, but there are regional differences in the number of pulses evoked, in their delay, and in their site of origin.", "contents": "Delayed initiation of SS1 pulses in the sea anemone Calliactis parasitica: evidence for a fourth conducting system. 1. Single electrical shocks to the column sometimes elicit a series of 1-6 pulses in the SS1 (ectodermal slow system) but the first pulse does not appear until 5-28 s after stimulation. These pulses occur in addition to the early SS1 pulse which follows every shock and which has a conduction delay of less than 1 s. 2. The threshold of the delayed SS1 response is different from the thresholds of the three known conducting systems (through-conducting nerve net, SS1, and SS2). 3. In the case of stimulation of the column, the delayed SS1 pulses do not arise at the point of stimulation but probably originate in the tentacles or upper column. The pulse origin can shift during a single burst. 4. The pathway from the point of stimulation to the site of origin of delayed SS1 pulses is endodermal. We propose that this pathway represents a fourth conducting system (Delayed Initiation System--DIS). The DIS must connect, across the mesogloea, with the ectodermal SS1. The long pulse delay and repetitive firing may derive from pacemaker activity in the DIS. The DIS pacemakers closely resemble the pacemakers connected to the through-conducting nerve net. The DIS may be neuronal. 5. Delayed SS1 pulse bursts from unattached anemones showed an earlier onset, and more pulses/burst, than those from attached anemones. 6. Delayed SS1 pulses can also be evoked by electrical, and in some cases mechanical, stimulation of the pedal disc, tentacles, and pharynx, but there are regional differences in the number of pulses evoked, in their delay, and in their site of origin."}
{"id": "PMID:14221", "title": "Oxygen-binding properties of hemoglobins from estivating and active African lungfish.", "content": "The oxygen-binding characteristics and the multiplicity of the stripped hemoglobiin from active lungfish Protopterus amphibius, are the same as in specimens that have been estivating for about 30 months, showing that alteration in the hemoglobin molecules is not involved in the earlier reported increase in oxygen affinity of whole blood during estivation (Johansen et al., '76). At pH 7.0 and 26 degrees C the hemolysates show a high oxygen affinity (P50 = 3.1 Torr), a Bohr factor (delta log P50/delta pH) of - 0.33, and a cooperativity coefficient (n) of 1.7. Between 15 and 26 degrees C, the apparent heat of oxygenation (delta H) is - 8.6 Kcal-mole-1 at pH 7.0, corresponding with data for other fish. A low sensitivity of oxygen affinity to urea appears to be adaptive to the high urea concentrations in estivating lungfish. The salt sensitivity is, however, similar to human hemoglobin. The hemoglobin consists of two major (electrophoretically anodal) components, which differ slightly in oxygen affinity but are both sensitive to pH and nucleoside triphosphates (NTP). Guanosine triphosphate (GTP), the major erythrocytic organic phosphate, however, depresses the oxygen affinity of the composite and separated hemoglobins more effectively than ATP suggesting that GTP is the primary modulator of oxygen affinity. Comparative measurements reveal only one major hemoglobin component in P. annectens which has a markedly lower oxygen affinity and phosphate sensitivity than P. amphibius hemoglobins and thus seems less pliable to phosphate-mediated variation in oxygen affinity. The data are discussed in relation to the hemoglobin systems of other fish.", "contents": "Oxygen-binding properties of hemoglobins from estivating and active African lungfish. The oxygen-binding characteristics and the multiplicity of the stripped hemoglobiin from active lungfish Protopterus amphibius, are the same as in specimens that have been estivating for about 30 months, showing that alteration in the hemoglobin molecules is not involved in the earlier reported increase in oxygen affinity of whole blood during estivation (Johansen et al., '76). At pH 7.0 and 26 degrees C the hemolysates show a high oxygen affinity (P50 = 3.1 Torr), a Bohr factor (delta log P50/delta pH) of - 0.33, and a cooperativity coefficient (n) of 1.7. Between 15 and 26 degrees C, the apparent heat of oxygenation (delta H) is - 8.6 Kcal-mole-1 at pH 7.0, corresponding with data for other fish. A low sensitivity of oxygen affinity to urea appears to be adaptive to the high urea concentrations in estivating lungfish. The salt sensitivity is, however, similar to human hemoglobin. The hemoglobin consists of two major (electrophoretically anodal) components, which differ slightly in oxygen affinity but are both sensitive to pH and nucleoside triphosphates (NTP). Guanosine triphosphate (GTP), the major erythrocytic organic phosphate, however, depresses the oxygen affinity of the composite and separated hemoglobins more effectively than ATP suggesting that GTP is the primary modulator of oxygen affinity. Comparative measurements reveal only one major hemoglobin component in P. annectens which has a markedly lower oxygen affinity and phosphate sensitivity than P. amphibius hemoglobins and thus seems less pliable to phosphate-mediated variation in oxygen affinity. The data are discussed in relation to the hemoglobin systems of other fish."}
{"id": "PMID:14222", "title": "Correlation of structural transitions in coliphage R17 with its loss of infectivity.", "content": "A circular dichroism comparative study of isolated and in situ phage R17 RNA reveals in both cases the same degree of base pairing. However, thermal circular dichroism melting profiles exhibit the presence of free energy of interaction between RNA and capsid protein. It is apparent that the capsid stabilizes the RNA structure with and without the addition of Mg2+. A close RNA capsid association is also derived from pH titration circular dichroism studies. The pH melting of the RNA in situ starts to occur about 0-5 pH unit higher with and without the addition of Mg2+ than the acid denaturation of isolated RNA. A direct correlation between bathochromic CD peak shift to the main position band and loss of survivors is noted for the thermal melting as well as pH titration experiments. It is suggested that the heat and pH induced conformational alterations of R17 RNA in situ coinciding with loss of infectivity occur after an in situ alteration of nucleic acid-capsid protein interaction.", "contents": "Correlation of structural transitions in coliphage R17 with its loss of infectivity. A circular dichroism comparative study of isolated and in situ phage R17 RNA reveals in both cases the same degree of base pairing. However, thermal circular dichroism melting profiles exhibit the presence of free energy of interaction between RNA and capsid protein. It is apparent that the capsid stabilizes the RNA structure with and without the addition of Mg2+. A close RNA capsid association is also derived from pH titration circular dichroism studies. The pH melting of the RNA in situ starts to occur about 0-5 pH unit higher with and without the addition of Mg2+ than the acid denaturation of isolated RNA. A direct correlation between bathochromic CD peak shift to the main position band and loss of survivors is noted for the thermal melting as well as pH titration experiments. It is suggested that the heat and pH induced conformational alterations of R17 RNA in situ coinciding with loss of infectivity occur after an in situ alteration of nucleic acid-capsid protein interaction."}
{"id": "PMID:14223", "title": "The use of tris-HCl buffer for inoculation of tomato protoplasts with tobacco mosaic virus.", "content": "When tris-HCL was used as the buffer for inoculation of tomato protoplasts with tobacco mosaic virus, a greater proportion became infected than when phosphate was used. Using 0-05 M-tris-HCl buffer, pH 8-0, in the presence of poly-L-ornithine or poly-D-lysine, 50 to 80 % infection was obtained.", "contents": "The use of tris-HCl buffer for inoculation of tomato protoplasts with tobacco mosaic virus. When tris-HCL was used as the buffer for inoculation of tomato protoplasts with tobacco mosaic virus, a greater proportion became infected than when phosphate was used. Using 0-05 M-tris-HCl buffer, pH 8-0, in the presence of poly-L-ornithine or poly-D-lysine, 50 to 80 % infection was obtained."}
{"id": "PMID:14224", "title": "Adsorption of phage P22 to Salmonella typhimurium.", "content": "Adsorption of phage P22 to its receptor in the lipopolysaccharide (LPS) of the envelope of Salmonella typhimurium is accompanied by a hydrolytic cleavage of the O polysaccharide chain. The enzyme, and endorhamnosidase, is found in the phage tail. Propagation of a mutant of phage P22, containing two amber mutations, under restrictive conditions permitted isolation of phage tail parts with endorhamnosidase activity. The tail parts, purified by ion exchange chromatography, were shown to be homogenous by polyacrylamide gradient gel electrophoresis, isoelectric focusing in polyacrylamide gel electrophoresis and crossed immunoelectrophoresis. The mol. wt. was estimated to 240000. The optimal pH range for glycosidase activity was 5 to 7 and optimal temperature 37 degrees C. Hydrolysis of the O polysaccharide chain, when estimated with whole bacteria as the substrate, did not seem to be influenced by the cation concentration. Eclipse of P22 phage particles to whole bacteria was likewise uninfluenced by the cation concentration in the reaction mixture, but eclipse by isolated receptor containing LPS required cations. The optimal concentration for divalent cations was 2 X 10(-3) M, for trivalent cations 1 X 10(-3) M.", "contents": "Adsorption of phage P22 to Salmonella typhimurium. Adsorption of phage P22 to its receptor in the lipopolysaccharide (LPS) of the envelope of Salmonella typhimurium is accompanied by a hydrolytic cleavage of the O polysaccharide chain. The enzyme, and endorhamnosidase, is found in the phage tail. Propagation of a mutant of phage P22, containing two amber mutations, under restrictive conditions permitted isolation of phage tail parts with endorhamnosidase activity. The tail parts, purified by ion exchange chromatography, were shown to be homogenous by polyacrylamide gradient gel electrophoresis, isoelectric focusing in polyacrylamide gel electrophoresis and crossed immunoelectrophoresis. The mol. wt. was estimated to 240000. The optimal pH range for glycosidase activity was 5 to 7 and optimal temperature 37 degrees C. Hydrolysis of the O polysaccharide chain, when estimated with whole bacteria as the substrate, did not seem to be influenced by the cation concentration. Eclipse of P22 phage particles to whole bacteria was likewise uninfluenced by the cation concentration in the reaction mixture, but eclipse by isolated receptor containing LPS required cations. The optimal concentration for divalent cations was 2 X 10(-3) M, for trivalent cations 1 X 10(-3) M."}
{"id": "PMID:14227", "title": "Traditional versus individualized nursing instruction: comparison of State Board Examination scores as a result of these two methods of nursing instruction.", "content": "There is no evidence as a result of this study to preclude that the LEGS Program is not worthwhile. Achievement of State Board Examination Scores have not suffered as a result of this method of instruction, at least in the three schools studied. Statistically, there is no significant difference in mean achievement of State Board Examination Scores as a result of the two methods of nursing instruction. Efforts should be made to improve upon the further investigate this new method of nursing instruction.", "contents": "Traditional versus individualized nursing instruction: comparison of State Board Examination scores as a result of these two methods of nursing instruction. There is no evidence as a result of this study to preclude that the LEGS Program is not worthwhile. Achievement of State Board Examination Scores have not suffered as a result of this method of instruction, at least in the three schools studied. Statistically, there is no significant difference in mean achievement of State Board Examination Scores as a result of the two methods of nursing instruction. Efforts should be made to improve upon the further investigate this new method of nursing instruction."}
{"id": "PMID:14229", "title": "Teaching patient assessment: the pros & cons of clinical rounds.", "content": "The first step in the nursing process is assessment. Facility with patient assessment skills precludes planning, implementing and evaluating patient care. Teaching patient assessment is time consuming and potentially anxiety-provoking. Classroom lectures and practice labs are not enough if students are to learn how to assess patients with pathophysiological responses. We found that clinical rounds on select patientw was a most important adjunct. Coordinating and conducting clinical rounds presents many problems but faculty and students are in complete agreement that the advantages far outweigh the disadvantages. We are hoping that others can \"go to school\" on some of our experiences as we will continue to do so.", "contents": "Teaching patient assessment: the pros & cons of clinical rounds. The first step in the nursing process is assessment. Facility with patient assessment skills precludes planning, implementing and evaluating patient care. Teaching patient assessment is time consuming and potentially anxiety-provoking. Classroom lectures and practice labs are not enough if students are to learn how to assess patients with pathophysiological responses. We found that clinical rounds on select patientw was a most important adjunct. Coordinating and conducting clinical rounds presents many problems but faculty and students are in complete agreement that the advantages far outweigh the disadvantages. We are hoping that others can \"go to school\" on some of our experiences as we will continue to do so."}
{"id": "PMID:14233", "title": "Instructor and course evaluation based on student-identified criteria.", "content": "Students have come to school for an education and it is their right to evaluate the quality of the education they are receiving. They should not have to demand or even ask for the privilege of saying what they think. Instructors should be providing the opportunity for evaluation by requesting that information from the students. No value judgment can be totally objective, but an instrument composed of mutually agreed upon statements should encourage the greatest possible degree of objectivity. Using one accepted form throughout the school, all students would be considering the same characteristics and traits for every instructor and course evaluated. Each instructor would receive similar information about personal performance and about the course presented. Students would be free to talk to the faculty or to add comments if they so desired; but, a questionnaire used in every course would allow and even encourage responses from every student enrolled. Faculty responsibility would not end with the preparation and implementation of an evaluation instrument. Instructors would have to let the students know their opinions are important and will be considered in curricular and instructional decisions. Faculty and students would be communicating and hopefully fulfilling the needs of and responsibilities to each other.", "contents": "Instructor and course evaluation based on student-identified criteria. Students have come to school for an education and it is their right to evaluate the quality of the education they are receiving. They should not have to demand or even ask for the privilege of saying what they think. Instructors should be providing the opportunity for evaluation by requesting that information from the students. No value judgment can be totally objective, but an instrument composed of mutually agreed upon statements should encourage the greatest possible degree of objectivity. Using one accepted form throughout the school, all students would be considering the same characteristics and traits for every instructor and course evaluated. Each instructor would receive similar information about personal performance and about the course presented. Students would be free to talk to the faculty or to add comments if they so desired; but, a questionnaire used in every course would allow and even encourage responses from every student enrolled. Faculty responsibility would not end with the preparation and implementation of an evaluation instrument. Instructors would have to let the students know their opinions are important and will be considered in curricular and instructional decisions. Faculty and students would be communicating and hopefully fulfilling the needs of and responsibilities to each other."}
{"id": "PMID:14237", "title": "An experience with a systems approach to curriculum design.", "content": "Learning system design, based on general systems theory, is a powerful facilitator for planning and implementing programs of curriculum and instruction. Curriculum planners are directed to a practical consideration of all systems components, and an awareness of their interrelatedness. Specifically they must deal with: Problem areas or barriers to success; the need to define and choose explicit outcomes; ways to make the curriculum operational; and a specific plan for program assessment. The systems process is value free and content free. Values are generated as content is selected and fitted into the system components. Therefore the system input is a crucial factor in the quality of the system. I have attempted to share some aspects of systems methodology which were very useful in the experience of designing a program for the education of gerontological nurse practitioners.", "contents": "An experience with a systems approach to curriculum design. Learning system design, based on general systems theory, is a powerful facilitator for planning and implementing programs of curriculum and instruction. Curriculum planners are directed to a practical consideration of all systems components, and an awareness of their interrelatedness. Specifically they must deal with: Problem areas or barriers to success; the need to define and choose explicit outcomes; ways to make the curriculum operational; and a specific plan for program assessment. The systems process is value free and content free. Values are generated as content is selected and fitted into the system components. Therefore the system input is a crucial factor in the quality of the system. I have attempted to share some aspects of systems methodology which were very useful in the experience of designing a program for the education of gerontological nurse practitioners."}
{"id": "PMID:14239", "title": "Evaluating the nonverbal communication skills of nursing students.", "content": "This study examined the accuracy rate of judging nonverbal skills used by nursing students in communicating with patients. Self-ratings of the students were compared with composite instructor ratings to find areas of disagreement regarding the quality of the nonverbal skills. Students who rated their nonverbal acuity higher than the instructors and students who rated their nonverbal acuity lower than the instructors were parceled out of the total sample of 92 senior nursing students enrolled in a baccalaureate program. Nonverbal acuity was measured by asking subjects to identify nonverbal information about emotional states from pictures. A November Picture Test consisting of 120 pictorial items was utilized as the dependent variable. Results showed that almost one half of the sample disagreed with the instructor rating applied to their nonverbal skills with patients. The differences between the groups was significant at the 0.05 level and the students were accurate in designating the direction of difference. Results are discussed in relation to clinical evaluation by both faculty and students in appraising communication skills. Implications such as grade inflation are discussed and recommendations for further study are covered.", "contents": "Evaluating the nonverbal communication skills of nursing students. This study examined the accuracy rate of judging nonverbal skills used by nursing students in communicating with patients. Self-ratings of the students were compared with composite instructor ratings to find areas of disagreement regarding the quality of the nonverbal skills. Students who rated their nonverbal acuity higher than the instructors and students who rated their nonverbal acuity lower than the instructors were parceled out of the total sample of 92 senior nursing students enrolled in a baccalaureate program. Nonverbal acuity was measured by asking subjects to identify nonverbal information about emotional states from pictures. A November Picture Test consisting of 120 pictorial items was utilized as the dependent variable. Results showed that almost one half of the sample disagreed with the instructor rating applied to their nonverbal skills with patients. The differences between the groups was significant at the 0.05 level and the students were accurate in designating the direction of difference. Results are discussed in relation to clinical evaluation by both faculty and students in appraising communication skills. Implications such as grade inflation are discussed and recommendations for further study are covered."}
{"id": "PMID:14240", "title": "The effects of feeding on arterial blood gases and lung mechanics in newborn infants recovering from respiratory disease.", "content": "Fifteen infants recovering from neonatal respiratory disease had arterial blood gases and lung mechanics measured 5 minutes before bolus feeds and at 5, 10, 20, and 30 minutes after feeding to determine physiologic effects of feeding. PaO2 fell significantly from prefeeding values at 5, 10, and 20 minutes after feeds. Mean prefeeding pH and base excess values were significantly different from mean postfeeding values at 5, 10, 20, and 30 minutes, respectively. PaCO2 remained unchanged before and after feeding. Heart rate and systolic and diastolic blood pressure did not change throughout the study. Dynamic lung compliance, respiratory, rate, and tidal volume did not change significantly but there was a trend toward increase in tidal volume. Mean minute volume rose with time as a consequence of the increased tidal volume. Work of breathing remained unchanged at 10 and 20 minutes postfeed and increased slightly at 30 minutes; this was due to a small increase in both elastic and viscous work components at this time.", "contents": "The effects of feeding on arterial blood gases and lung mechanics in newborn infants recovering from respiratory disease. Fifteen infants recovering from neonatal respiratory disease had arterial blood gases and lung mechanics measured 5 minutes before bolus feeds and at 5, 10, 20, and 30 minutes after feeding to determine physiologic effects of feeding. PaO2 fell significantly from prefeeding values at 5, 10, and 20 minutes after feeds. Mean prefeeding pH and base excess values were significantly different from mean postfeeding values at 5, 10, 20, and 30 minutes, respectively. PaCO2 remained unchanged before and after feeding. Heart rate and systolic and diastolic blood pressure did not change throughout the study. Dynamic lung compliance, respiratory, rate, and tidal volume did not change significantly but there was a trend toward increase in tidal volume. Mean minute volume rose with time as a consequence of the increased tidal volume. Work of breathing remained unchanged at 10 and 20 minutes postfeed and increased slightly at 30 minutes; this was due to a small increase in both elastic and viscous work components at this time."}
{"id": "PMID:14241", "title": "Efficacy of caffeine in treatment of apnea in the low-birth-weight infant.", "content": "The efficacy of caffeine citrate in the management of apnea in the newborn infant was evaluated. Caffeine citrate was given to 18 preterm neonates with recurrent apneic spells. Mean (+/- SE) birth weight and gestational age were 1,065.0 +/- 71.9 gm and 27.5 +/- 0.6 weeks, respectively. Mean age at onset of apnea and at initiation of caffeine treatment was 6.5 +/- 3.7 days and 18.2 +/- 4.9 days, respectively. Caffeine citrate was administered with a loading dose of 20 mg/kg intravenously followed within two to three days by 5 to 10 mg/kg once or twice daily. All infants except one showed a significant decrease in the frequency of apneic episodes associated with caffeine therapy. Mean frequencies of apneic spells were 13.6 +/- 2.5 and 2.1 +/- 0.6 apnea per day before and after initiation of caffeine treatment, respectively. Respiratory rate was increased, and blood [h]+ion concentration and Pco2 were decreased. The data suggest that caffeine is an effective pharmacologic respirogenic agent in the preterm infant with apnea.", "contents": "Efficacy of caffeine in treatment of apnea in the low-birth-weight infant. The efficacy of caffeine citrate in the management of apnea in the newborn infant was evaluated. Caffeine citrate was given to 18 preterm neonates with recurrent apneic spells. Mean (+/- SE) birth weight and gestational age were 1,065.0 +/- 71.9 gm and 27.5 +/- 0.6 weeks, respectively. Mean age at onset of apnea and at initiation of caffeine treatment was 6.5 +/- 3.7 days and 18.2 +/- 4.9 days, respectively. Caffeine citrate was administered with a loading dose of 20 mg/kg intravenously followed within two to three days by 5 to 10 mg/kg once or twice daily. All infants except one showed a significant decrease in the frequency of apneic episodes associated with caffeine therapy. Mean frequencies of apneic spells were 13.6 +/- 2.5 and 2.1 +/- 0.6 apnea per day before and after initiation of caffeine treatment, respectively. Respiratory rate was increased, and blood [h]+ion concentration and Pco2 were decreased. The data suggest that caffeine is an effective pharmacologic respirogenic agent in the preterm infant with apnea."}
{"id": "PMID:14242", "title": "Nucleophilic addition of bisulfite ion to prostaglandins E2 and A2: implication in aqueous stability.", "content": "Evidence is presented to indicate that the bisulfite ion (HSO3-) adds across the C-9 carbonyl group of dinoprostone (prostaglandin E2) and across the delta 10,11- bond of prostaglandin A2. At room temperature, the apparent equilibrium constant, determined by phase solubility analysis, circular dichroism, UV spectroscopy, and partitioning, for the formation of the bisulfite adduct of dinoprostone is about 7.5 M-1 at neutral pH. From this result and a free energy relationship reported in the literature for the thermodynamics of nucleophilic addition to carbonyl groups, it is concluded that the chemical reactivity of the C-9 carbonyl group of dinoprostone is not high enough to improve aqueous stability through reversible one-step nucleophilic reactions. However, from a series of kinetic experiments, it is concluded that the equilibrium is extremely favorable for the formation of the bisulfite adduct of prostaglandin A2 over pH 4-8 at room temperature. The second-order rate constant for the attack of sulfite ion (SO3 2-) to prostaglandin A2 is 1.75 sec-1 M-1.", "contents": "Nucleophilic addition of bisulfite ion to prostaglandins E2 and A2: implication in aqueous stability. Evidence is presented to indicate that the bisulfite ion (HSO3-) adds across the C-9 carbonyl group of dinoprostone (prostaglandin E2) and across the delta 10,11- bond of prostaglandin A2. At room temperature, the apparent equilibrium constant, determined by phase solubility analysis, circular dichroism, UV spectroscopy, and partitioning, for the formation of the bisulfite adduct of dinoprostone is about 7.5 M-1 at neutral pH. From this result and a free energy relationship reported in the literature for the thermodynamics of nucleophilic addition to carbonyl groups, it is concluded that the chemical reactivity of the C-9 carbonyl group of dinoprostone is not high enough to improve aqueous stability through reversible one-step nucleophilic reactions. However, from a series of kinetic experiments, it is concluded that the equilibrium is extremely favorable for the formation of the bisulfite adduct of prostaglandin A2 over pH 4-8 at room temperature. The second-order rate constant for the attack of sulfite ion (SO3 2-) to prostaglandin A2 is 1.75 sec-1 M-1."}
{"id": "PMID:14243", "title": "Use of microcapsules as timed-release parenteral dosage form: application as radiopharmaceutical imaging agent.", "content": "The development of a new type of parenteral dosage form is described. A system of microencapsulation was formulated which produced microcapsules containing a water-soluble core material. The basic microencapsulation system could be altered to produce microcapsules with varied timed-release characteristics. Tracer methodology was employed as a sensitive and versatile analytical tool for the development and evaluation of the microencapsulation system. The core material was labeled by neutron activation after microcapsule formulation, which eliminated the radiation hazard and contamination problems that could occur during formulation with a labeled core material. Both in vitro and in vivo testing showed that the release patterns of labeled core material could be altered and detected. The microcapsules developed have potential as a timed-release parenteral dosage form and as an organ-imaging radiopharmaceutical.", "contents": "Use of microcapsules as timed-release parenteral dosage form: application as radiopharmaceutical imaging agent. The development of a new type of parenteral dosage form is described. A system of microencapsulation was formulated which produced microcapsules containing a water-soluble core material. The basic microencapsulation system could be altered to produce microcapsules with varied timed-release characteristics. Tracer methodology was employed as a sensitive and versatile analytical tool for the development and evaluation of the microencapsulation system. The core material was labeled by neutron activation after microcapsule formulation, which eliminated the radiation hazard and contamination problems that could occur during formulation with a labeled core material. Both in vitro and in vivo testing showed that the release patterns of labeled core material could be altered and detected. The microcapsules developed have potential as a timed-release parenteral dosage form and as an organ-imaging radiopharmaceutical."}
{"id": "PMID:14244", "title": "Oxidation photosensitized by tetracyclines.", "content": "Irradiation with 365-nm UV light of aerated aqueous solutions of tetracycline gives rise to oxygen uptake when the pH of the solution is above 7.5. The kinetics of the reaction were followed using a polarographic oxygen electrode at a range of pH values for seven currently prescribed tetracyclines. Variation of tetracycline concentration, UV light intensity, and temperature showed the characteristics normally associated with a sensitized photo-oxygenation mechanism rather than a free-radical process. Copper(II) ions inhibited the photo-oxidation of tetracycline, apparently by complex formation. The tetracyclines were tested for photosensitizing capability with oxidizable acceptors. In aqueous solution, no photosensitizing effect could be seen, but methanol solutions of 2,5-dimethylfuran and dl-limonene were oxidized at considerably increased rates when small amounts of tetracyclines were present. This observations has implications for the mechanism of in vivo photosensitivity reactions that occur when tetracyclines are taken internally.", "contents": "Oxidation photosensitized by tetracyclines. Irradiation with 365-nm UV light of aerated aqueous solutions of tetracycline gives rise to oxygen uptake when the pH of the solution is above 7.5. The kinetics of the reaction were followed using a polarographic oxygen electrode at a range of pH values for seven currently prescribed tetracyclines. Variation of tetracycline concentration, UV light intensity, and temperature showed the characteristics normally associated with a sensitized photo-oxygenation mechanism rather than a free-radical process. Copper(II) ions inhibited the photo-oxidation of tetracycline, apparently by complex formation. The tetracyclines were tested for photosensitizing capability with oxidizable acceptors. In aqueous solution, no photosensitizing effect could be seen, but methanol solutions of 2,5-dimethylfuran and dl-limonene were oxidized at considerably increased rates when small amounts of tetracyclines were present. This observations has implications for the mechanism of in vivo photosensitivity reactions that occur when tetracyclines are taken internally."}
{"id": "PMID:14245", "title": "Chemical ionization mass spectra of phenothiazine derivatives and their oxygenated analogs.", "content": "Twenty-nine derivatives of phenothiazine formed relatively stable ions by proton capture under conditions of chemical ionization, using methane or isobutane as reagent gas. Fragments of generally low abundance formed by simple bond cleavage in the trimethylene portion of the side chain and by loss of water or hydrogen halide. Mass spectra obtained from pyrolyzates of amine salts and from the corresponding free bases were essentially identical.", "contents": "Chemical ionization mass spectra of phenothiazine derivatives and their oxygenated analogs. Twenty-nine derivatives of phenothiazine formed relatively stable ions by proton capture under conditions of chemical ionization, using methane or isobutane as reagent gas. Fragments of generally low abundance formed by simple bond cleavage in the trimethylene portion of the side chain and by loss of water or hydrogen halide. Mass spectra obtained from pyrolyzates of amine salts and from the corresponding free bases were essentially identical."}
{"id": "PMID:14246", "title": "Effect of chloroquine adsorption on acid reactivity of magnesium trisilicate.", "content": "Due to the adsorption of chloroquine by magnesium trisilicate, both the BP acid absorption test and the rate of hydrochloric acid uptake, as monitored by pH measurements, were significantly reduced. This reduction was dependent on the amount of chloroquine adsorbed, since multilayer adsorption produced relatively more suppressive effects than did monolayer adsorption. The presence of adsorbed chloroquine also decreased the amounts of magnesium released in an acid medium. The inhibition of the antacid property due to chloroquine adsorption may be attributed to the occupation of the reactive sites of the antacid surface by chloroquine and to a reduction of the surface of the antacid due to flocculation of the particles.", "contents": "Effect of chloroquine adsorption on acid reactivity of magnesium trisilicate. Due to the adsorption of chloroquine by magnesium trisilicate, both the BP acid absorption test and the rate of hydrochloric acid uptake, as monitored by pH measurements, were significantly reduced. This reduction was dependent on the amount of chloroquine adsorbed, since multilayer adsorption produced relatively more suppressive effects than did monolayer adsorption. The presence of adsorbed chloroquine also decreased the amounts of magnesium released in an acid medium. The inhibition of the antacid property due to chloroquine adsorption may be attributed to the occupation of the reactive sites of the antacid surface by chloroquine and to a reduction of the surface of the antacid due to flocculation of the particles."}
{"id": "PMID:14248", "title": "Prenatal administration of levorphanol or dextrorphan to the rat: analgesic effect of morphine in the offspring.", "content": "We have recently demonstrated that prenatal administration of morphine to the rat results in tolerance to the analgesic effects of morphine in the offspring at 3 to 11 weeks of age. To extend these findings, levorphanol or dextrorphan was administered to female CFE rats during days 5 to 12 of gestation. Control animals were injected with 0.9% saline on the same schedule. At 5 weeks of age all offspring were tested with graded doses of morphine in the hot-plate test for analgesia. Morphine produced a dose-related increase in analgesia in all offspring, but the effect of morphine in the offspring of levorphanol-treated females was significantly reduced compared to the offspring of saline-treated females; the analgesic effect of morphine did not differ between the offspring of the dextrorphan- and saline-treated females. The analgesic effect of morphine remained reduced in 9-week old offspring of levorphanol-treated females compared to the corresponding offspring of females that had received saline. Diminished analgesic activity of morphine in the offspring of levorphanol-treated females compared to the offspring of females that had received dextrorphan or saline was still observed even when the offspring were rendered tolerant to morphine by daily drug injections over a period of 5 days. Thus, the protracted tolerance to the analgesic effects of morphine can also be produced by a morphine congener (levorphanol), but not by its analgesically inactive (+) isomer (dextrorphan).", "contents": "Prenatal administration of levorphanol or dextrorphan to the rat: analgesic effect of morphine in the offspring. We have recently demonstrated that prenatal administration of morphine to the rat results in tolerance to the analgesic effects of morphine in the offspring at 3 to 11 weeks of age. To extend these findings, levorphanol or dextrorphan was administered to female CFE rats during days 5 to 12 of gestation. Control animals were injected with 0.9% saline on the same schedule. At 5 weeks of age all offspring were tested with graded doses of morphine in the hot-plate test for analgesia. Morphine produced a dose-related increase in analgesia in all offspring, but the effect of morphine in the offspring of levorphanol-treated females was significantly reduced compared to the offspring of saline-treated females; the analgesic effect of morphine did not differ between the offspring of the dextrorphan- and saline-treated females. The analgesic effect of morphine remained reduced in 9-week old offspring of levorphanol-treated females compared to the corresponding offspring of females that had received saline. Diminished analgesic activity of morphine in the offspring of levorphanol-treated females compared to the offspring of females that had received dextrorphan or saline was still observed even when the offspring were rendered tolerant to morphine by daily drug injections over a period of 5 days. Thus, the protracted tolerance to the analgesic effects of morphine can also be produced by a morphine congener (levorphanol), but not by its analgesically inactive (+) isomer (dextrorphan)."}
{"id": "PMID:14249", "title": "Effects of maternal ethanol ingestion on amine uptake into synaptosomes of fetal and neonatal rat brain.", "content": "Pregnant rats were kept on an ethanol-containing (6.8% v/v) liquid diet either from the 13th or 18th day of gestation. In pups exposed to ethanol from the 13th day of gestation, synaptosomal uptake of 3H-tyramine and its conversion to 3H-octopamine were increased initially and exposure to ethanol from the 18th day of gestation produced increases in synaptosomal uptake and conversion for longer periods. These changes were not observed in adult rats administered ethanol. Brain tyrosin hydroxylase activity in the developing rats was unaltered by continuous exposure to ethanol. Withdrawal from ethanol either at 0, 3 or 5 days of age enhanced the tendancy toward increased synaptosomal uptake and conversion, but the magnitude of change depended upon the time of exposure and the age at which withdrawal was initiated. These results suggest that maternal ethanol ingestion can affect synaptic function in the developing central noradrenergic system, with consequent alterations in neurotransmitter uptake and storage.", "contents": "Effects of maternal ethanol ingestion on amine uptake into synaptosomes of fetal and neonatal rat brain. Pregnant rats were kept on an ethanol-containing (6.8% v/v) liquid diet either from the 13th or 18th day of gestation. In pups exposed to ethanol from the 13th day of gestation, synaptosomal uptake of 3H-tyramine and its conversion to 3H-octopamine were increased initially and exposure to ethanol from the 18th day of gestation produced increases in synaptosomal uptake and conversion for longer periods. These changes were not observed in adult rats administered ethanol. Brain tyrosin hydroxylase activity in the developing rats was unaltered by continuous exposure to ethanol. Withdrawal from ethanol either at 0, 3 or 5 days of age enhanced the tendancy toward increased synaptosomal uptake and conversion, but the magnitude of change depended upon the time of exposure and the age at which withdrawal was initiated. These results suggest that maternal ethanol ingestion can affect synaptic function in the developing central noradrenergic system, with consequent alterations in neurotransmitter uptake and storage."}
{"id": "PMID:14250", "title": "Saluretic and uricosuric effects of (6, 7-dichloro-2-methyl=1-oxo-2-phenyl-5-indanyloxy) acetic acid (MK-196) in the chimpanzee.", "content": "The saluretic and uricosuric responses elicited by a novel agent, MK-196, have been studied in a great ape, the chimpanzee. This agent is orally active at very low doses and has a prolonged duration of action. Probenecid does not appear to influence the saluretic and uricosuric properties of MK-196. Net tubular secretion of urate was reduced by MK-196. Urinary pH changes did not compromise the efficacy of this new agent. On a dose basis, MK-196 was more saluretic (and uricosuric) than ethacrynic acid or furosemide and possessed a longer duration of action. Because of the marked natriuresis caused by MK-196, some increase in potassium excretion occurred.", "contents": "Saluretic and uricosuric effects of (6, 7-dichloro-2-methyl=1-oxo-2-phenyl-5-indanyloxy) acetic acid (MK-196) in the chimpanzee. The saluretic and uricosuric responses elicited by a novel agent, MK-196, have been studied in a great ape, the chimpanzee. This agent is orally active at very low doses and has a prolonged duration of action. Probenecid does not appear to influence the saluretic and uricosuric properties of MK-196. Net tubular secretion of urate was reduced by MK-196. Urinary pH changes did not compromise the efficacy of this new agent. On a dose basis, MK-196 was more saluretic (and uricosuric) than ethacrynic acid or furosemide and possessed a longer duration of action. Because of the marked natriuresis caused by MK-196, some increase in potassium excretion occurred."}
{"id": "PMID:14251", "title": "Renal excretion of a slauretic-uricosuric agent (MK-196) and interaction with a urate-retaining drug, pyrazinoate, in the chimpanzee.", "content": "The excretory pattern for MK-196 is ocmpatible with that of other weak organic acids such as salicylate and probenecid. Tubular secretion of MK-196 is strongly inhibitied by probenecid and high loads of p-aminohippurate. Urinary excretion of MK-196 is increased 10-fold when the urine is alkaline. Clearances of MK-196 were not corrected for plasma protein binding of the drug which is very high (greater than 99%). Bidirectional transport processes are operative in that MK-196 is secreted by the renal tubule and passively back diffuses across the tubular epithelium by a pH-dependent process. MK-196 is able to overcome pyrazinoate-induced urate retention, whereas probenecid is not when studied by conventional clearance techniques. The uricosuric activity of MK-196 appears to be somewhat less with pyrazinoate than in its absence. When MK-196 is administered prior to pyrazinoate an attenuated uricosuric response was observed. This finding cannot be ascribed to a temporal decline in uricosuric action. Diuresis and saluresis produced by MK-196 are not influenced by pyrazinoate. The interaction of MK=196 and pyrazinoate on urate excretion is in direct contrast to results obtained with probenecid and pyrazinoate. A model has been proposed to explain this unique finding.", "contents": "Renal excretion of a slauretic-uricosuric agent (MK-196) and interaction with a urate-retaining drug, pyrazinoate, in the chimpanzee. The excretory pattern for MK-196 is ocmpatible with that of other weak organic acids such as salicylate and probenecid. Tubular secretion of MK-196 is strongly inhibitied by probenecid and high loads of p-aminohippurate. Urinary excretion of MK-196 is increased 10-fold when the urine is alkaline. Clearances of MK-196 were not corrected for plasma protein binding of the drug which is very high (greater than 99%). Bidirectional transport processes are operative in that MK-196 is secreted by the renal tubule and passively back diffuses across the tubular epithelium by a pH-dependent process. MK-196 is able to overcome pyrazinoate-induced urate retention, whereas probenecid is not when studied by conventional clearance techniques. The uricosuric activity of MK-196 appears to be somewhat less with pyrazinoate than in its absence. When MK-196 is administered prior to pyrazinoate an attenuated uricosuric response was observed. This finding cannot be ascribed to a temporal decline in uricosuric action. Diuresis and saluresis produced by MK-196 are not influenced by pyrazinoate. The interaction of MK=196 and pyrazinoate on urate excretion is in direct contrast to results obtained with probenecid and pyrazinoate. A model has been proposed to explain this unique finding."}
{"id": "PMID:14255", "title": "Potential difference and the distribution of ions across the human red blood cell membrane; a study of the mechanism by which the fluorescent cation, diS-C3-(5) reports membrane potential.", "content": "1. The mechanism by which the fluorescent, cationic dye diS-C3-(5) responds to the membrane potential of red blood cells has been investigated. 2. The dye in aqueous solution absorbs most strongly at 650 nm. Addition of white, haemoglobin-free membranes red shifts the absorption maximum ca. 20 nm, while addition of membrane-free cell lysate results in the appearance of a new dye absorption peak at 590 nm. Thus the dye binds both to cell membranes and to cell contents. The component of the cytoplasm which binds the dye is non-dialysable, presumably haemoglobin. 3. Dye added to a suspension of intact cells shows a strong absorption at 590 nm indicating that the dye has bound to the cell contents and that the membrane is permeable to the dye. 4. The amount of dye which partitions into (and on to) the cells can be determined, as reported by Sims, Waggoner, Wang & Hoffman (1974), from the fluorescence of the dye remaining in the supernatant after the cells are centrifuged to the bottom of the suspension. In most conditions the proportion of the cell associated dye which is either free inside the cell or bound to the outside face of the membrane is negligible compared to the proportion bound to the cell contents. 5. On the assumption that the dye is not actively transported, the ratio of the equilibrium dye activities inside and outside the cell, ai/ao, is determined by the membrane potential according to the Nernst relation. Driving the membrane potenial negative then increases the cell associated dye by increasing the activity ratio and hence ai and the amount of dye bound to cell contents. 6. At the known Donnan equilibrium potential the internal dye activity can be calculated from the external activity. An empirical relation between cell associated dye and internal activity has been determined by measuring the dye partition between cells and medium at different external activities. 7. Using this empirial relation, and providing that any changes in cell composition do not affect the dye binding, the internal activity at any potential can be calculated from the measured amount of cell associated dye. The external activity can be estimated fluorimetrically. The membrane potential is then calculated from the activity ratio. 8. The membrane potenial of cells has been altered by adding valinomycin in the presence of different K gradients. Under the conditions used, the 'constant field' permeability for K-Val is 15-20 times that of Cl. 9. Dye binding to haemoglobin is influenced by pH and thus dye partitioning into cells changes with intracellular pH. Increasing intracellular pH increases the amount of dye partitioned, while decreasing pH decreases this amount. 10. When large potentials are produced with valinomycin there is no change in intracellular pH. This result indicates that in red blood cells intracellular pH is determined by the external pH and the Cl concentration ratio and not by the membrane potentials. 11. DiS-C3-(5) can be used to estimate potentials across resealed ghost membranes...", "contents": "Potential difference and the distribution of ions across the human red blood cell membrane; a study of the mechanism by which the fluorescent cation, diS-C3-(5) reports membrane potential. 1. The mechanism by which the fluorescent, cationic dye diS-C3-(5) responds to the membrane potential of red blood cells has been investigated. 2. The dye in aqueous solution absorbs most strongly at 650 nm. Addition of white, haemoglobin-free membranes red shifts the absorption maximum ca. 20 nm, while addition of membrane-free cell lysate results in the appearance of a new dye absorption peak at 590 nm. Thus the dye binds both to cell membranes and to cell contents. The component of the cytoplasm which binds the dye is non-dialysable, presumably haemoglobin. 3. Dye added to a suspension of intact cells shows a strong absorption at 590 nm indicating that the dye has bound to the cell contents and that the membrane is permeable to the dye. 4. The amount of dye which partitions into (and on to) the cells can be determined, as reported by Sims, Waggoner, Wang & Hoffman (1974), from the fluorescence of the dye remaining in the supernatant after the cells are centrifuged to the bottom of the suspension. In most conditions the proportion of the cell associated dye which is either free inside the cell or bound to the outside face of the membrane is negligible compared to the proportion bound to the cell contents. 5. On the assumption that the dye is not actively transported, the ratio of the equilibrium dye activities inside and outside the cell, ai/ao, is determined by the membrane potential according to the Nernst relation. Driving the membrane potenial negative then increases the cell associated dye by increasing the activity ratio and hence ai and the amount of dye bound to cell contents. 6. At the known Donnan equilibrium potential the internal dye activity can be calculated from the external activity. An empirical relation between cell associated dye and internal activity has been determined by measuring the dye partition between cells and medium at different external activities. 7. Using this empirial relation, and providing that any changes in cell composition do not affect the dye binding, the internal activity at any potential can be calculated from the measured amount of cell associated dye. The external activity can be estimated fluorimetrically. The membrane potential is then calculated from the activity ratio. 8. The membrane potenial of cells has been altered by adding valinomycin in the presence of different K gradients. Under the conditions used, the 'constant field' permeability for K-Val is 15-20 times that of Cl. 9. Dye binding to haemoglobin is influenced by pH and thus dye partitioning into cells changes with intracellular pH. Increasing intracellular pH increases the amount of dye partitioned, while decreasing pH decreases this amount. 10. When large potentials are produced with valinomycin there is no change in intracellular pH. This result indicates that in red blood cells intracellular pH is determined by the external pH and the Cl concentration ratio and not by the membrane potentials. 11. DiS-C3-(5) can be used to estimate potentials across resealed ghost membranes..."}
{"id": "PMID:14256", "title": "The Bohr effect on the reaction of carbon monoxide with fully oxygenated haemoglobin.", "content": "1. The rate at which CO displaces O2 from its combination with haemoglobin in solution, has been measured spectrophotometrically, using a rapid-mixing stopped-flow technique. 2. In the presence of CO2, the reaction proceeds by a unimolecular dissociation, with a rate constant r. 3. The relationship of the reciprocal of r to the ratio PO2/PCO is nonlinear, and a different curve is obtained at each CO concentration. 4. Measurements were made of the rate of the reaction when the pH was varied, with constant or varying PCO2. In both situations the value of r was found to have a miximum, for a given PO2/PCO ratio and CO cencentration, at pH 7.2. 5. An analysis of these results suggest that the Bohr effect, of pH and PCO2, is a dynamic equilibrium between four stable tertiary states of each of the alpha and beta chains. Each intermediatory complex has different rate constants for CO and O2.", "contents": "The Bohr effect on the reaction of carbon monoxide with fully oxygenated haemoglobin. 1. The rate at which CO displaces O2 from its combination with haemoglobin in solution, has been measured spectrophotometrically, using a rapid-mixing stopped-flow technique. 2. In the presence of CO2, the reaction proceeds by a unimolecular dissociation, with a rate constant r. 3. The relationship of the reciprocal of r to the ratio PO2/PCO is nonlinear, and a different curve is obtained at each CO concentration. 4. Measurements were made of the rate of the reaction when the pH was varied, with constant or varying PCO2. In both situations the value of r was found to have a miximum, for a given PO2/PCO ratio and CO cencentration, at pH 7.2. 5. An analysis of these results suggest that the Bohr effect, of pH and PCO2, is a dynamic equilibrium between four stable tertiary states of each of the alpha and beta chains. Each intermediatory complex has different rate constants for CO and O2."}
{"id": "PMID:14259", "title": "Interprofessional education of the new health practitioner.", "content": "This is a report of a survey of the interprofessional education activities included in 54 physician's assistant and 60 nurse practitioner programs. In a majority of such new health practitioner programs, the importance of interprofessional education as a part of training for team health care delivery has been recognized, and some structured interprofessional activity has been provided. A variety of methods are being used to achieve the objectives of effective team delivery of primary health care, including the mixing of students in both classroom and clinical settings and the inclusion of specific courses on role and professional identity. Seventy percent of physician's assistant students and 38 percent of nurse practitioner students in the programs included in the study have at least one classroom activity shared with another health profession group, most commonly medical students. Only a surprisingly small percentage of programs were involved in any evaluation of their interprofessional activities. In spite of the primary care orientation of new health practitioner programs, less than 40 percent offer clinical experience on a health team in a primary care setting.", "contents": "Interprofessional education of the new health practitioner. This is a report of a survey of the interprofessional education activities included in 54 physician's assistant and 60 nurse practitioner programs. In a majority of such new health practitioner programs, the importance of interprofessional education as a part of training for team health care delivery has been recognized, and some structured interprofessional activity has been provided. A variety of methods are being used to achieve the objectives of effective team delivery of primary health care, including the mixing of students in both classroom and clinical settings and the inclusion of specific courses on role and professional identity. Seventy percent of physician's assistant students and 38 percent of nurse practitioner students in the programs included in the study have at least one classroom activity shared with another health profession group, most commonly medical students. Only a surprisingly small percentage of programs were involved in any evaluation of their interprofessional activities. In spite of the primary care orientation of new health practitioner programs, less than 40 percent offer clinical experience on a health team in a primary care setting."}
{"id": "PMID:14265", "title": "Role of bacterial microflora in development of intestinal lesions from graft-versus-host reaction.", "content": "Acute secondary disease was induced in (C57BL X CBA)F1 mice by transplanting CBA bone marrow and spleen cells following lethal whole-body irradiation. The lesions of graft-versus-host (GvH) disease were scored quantitatively by counting of degenerated crypts in subcutaneous fetal gut implants that were free of bacteria. In conventional F1 mice the damage in F1 fetal gut was twice as great as in F1 fetal gut implants carried by decontaminated chimeras. CBA fetal gut implants developed substantial damage when present in conventional chimeras, but not when present in decontaminated chimeras. These results could be explained by assuming the presence of cross-reacting antigens on intestinal bacteria and in the gut epithelial tissue. They also explained the profound protection against delayed GvH mortality provided by removal of the intestinal microflora.", "contents": "Role of bacterial microflora in development of intestinal lesions from graft-versus-host reaction. Acute secondary disease was induced in (C57BL X CBA)F1 mice by transplanting CBA bone marrow and spleen cells following lethal whole-body irradiation. The lesions of graft-versus-host (GvH) disease were scored quantitatively by counting of degenerated crypts in subcutaneous fetal gut implants that were free of bacteria. In conventional F1 mice the damage in F1 fetal gut was twice as great as in F1 fetal gut implants carried by decontaminated chimeras. CBA fetal gut implants developed substantial damage when present in conventional chimeras, but not when present in decontaminated chimeras. These results could be explained by assuming the presence of cross-reacting antigens on intestinal bacteria and in the gut epithelial tissue. They also explained the profound protection against delayed GvH mortality provided by removal of the intestinal microflora."}
{"id": "PMID:14266", "title": "Observations upon calcium oxalate crystallization kinetics in simulated urine.", "content": "Two major etiologic theories of urinary stones are excessive saturation of urine with crystallizable substances or defects in inhibitors that allow relative supersaturation to occur. To date, it has been difficult to confirm the supersaturation theory in experiments using diffusion-limited crystallization systems because direct measurements of the nucleation process of crystallization could not be performed. We used well developed, continuous crystallizer techniques and adapted them from industrial use to the study of stone disease. Data derived from the experiments allow the absolute measurement of crystal growth rate and determination of nucleation rate. These methods were applied to study the calcium oxalate dihydrate (weddellite) system in artificial urine that lacked only proteinaceous components. Based on these experiments it was not possible to grow crystals large enough within 5 to 20 minutes to obstruct the collecting ducts of the kidney. Therefore, it appears that other processes, such as aggregation or stasis within tissues, may well be related to initiation of stone disease. Under the experimental conditions of this study nucleation rate exceeded growth rate. Therefore, multiple small particles are created at the expense of allowing larger particles to grow. Inhibitors can be tested rapidly in this system by adding them in concentrations compatible with those found in urine.", "contents": "Observations upon calcium oxalate crystallization kinetics in simulated urine. Two major etiologic theories of urinary stones are excessive saturation of urine with crystallizable substances or defects in inhibitors that allow relative supersaturation to occur. To date, it has been difficult to confirm the supersaturation theory in experiments using diffusion-limited crystallization systems because direct measurements of the nucleation process of crystallization could not be performed. We used well developed, continuous crystallizer techniques and adapted them from industrial use to the study of stone disease. Data derived from the experiments allow the absolute measurement of crystal growth rate and determination of nucleation rate. These methods were applied to study the calcium oxalate dihydrate (weddellite) system in artificial urine that lacked only proteinaceous components. Based on these experiments it was not possible to grow crystals large enough within 5 to 20 minutes to obstruct the collecting ducts of the kidney. Therefore, it appears that other processes, such as aggregation or stasis within tissues, may well be related to initiation of stone disease. Under the experimental conditions of this study nucleation rate exceeded growth rate. Therefore, multiple small particles are created at the expense of allowing larger particles to grow. Inhibitors can be tested rapidly in this system by adding them in concentrations compatible with those found in urine."}
{"id": "PMID:14268", "title": "[Bacteriological evaluation of clindamycin-2-phosphate (author's transl)].", "content": "Clindamycin-2-phosphate, a newly developed injectable antibiotic, was bacteriologically evaluated in comparison with the parent compound, clindamycin. Clindamycin-2-phosphate has a rather weak antibacterial activity. However, it is metabolized into clindamycin in vivo. And this parent compound shows strong activity against both gram-positive bacteria and gram-negative cocci. In vitro studies demonstrated that clindamycin-2-phosphate and clindamycin are affected by the pH of the medium used--the antibacterial activity becomes stronger as the medium is made more alkaline--while they are little affected by the size of the inoculum. In mice with experimental infections, clindamycin-2-phosphate showed about the same therapeutical effect as clindamycin in contrast with the former's inferior in vitro activity as compared with the latter.", "contents": "[Bacteriological evaluation of clindamycin-2-phosphate (author's transl)]. Clindamycin-2-phosphate, a newly developed injectable antibiotic, was bacteriologically evaluated in comparison with the parent compound, clindamycin. Clindamycin-2-phosphate has a rather weak antibacterial activity. However, it is metabolized into clindamycin in vivo. And this parent compound shows strong activity against both gram-positive bacteria and gram-negative cocci. In vitro studies demonstrated that clindamycin-2-phosphate and clindamycin are affected by the pH of the medium used--the antibacterial activity becomes stronger as the medium is made more alkaline--while they are little affected by the size of the inoculum. In mice with experimental infections, clindamycin-2-phosphate showed about the same therapeutical effect as clindamycin in contrast with the former's inferior in vitro activity as compared with the latter."}
{"id": "PMID:14269", "title": "[Use of clindamycin-2-phosphate in ophthalmology (author's transl)].", "content": "Clindamycin-2-phosphate was studied to evaluate its possible use in ophthalmology. 1. Sensitivity of organisms isolated from human clinical materials: Of 44 staphylococcal strains in vitro studied 13 were highly sensitive to 0.1 mug/ml and 28 were resistant to 100 mug/ml or more of clindamycin-2-phosphate. 2. In experiments with rabbits, clindamycin-2-phosphate showed superior penetration into the ocular tissues after intravenous injection than after intramuscular injection. 3. Clindamycin-2-phosphate was administered intramuscularly at the dose of 300 mg to 6 healthy volunteers. The blood concentrations of 6 cases averaged 3.2 mug/ml after 1 hour, and 0.8 mug/ml after 6 hours. 4. Fourteen patients with extraocular infection were treated with daily intramuscular administration of 300 mg of clindamycin-2-phosphate. All of them improved by the treatment, and no side effect was observed.", "contents": "[Use of clindamycin-2-phosphate in ophthalmology (author's transl)]. Clindamycin-2-phosphate was studied to evaluate its possible use in ophthalmology. 1. Sensitivity of organisms isolated from human clinical materials: Of 44 staphylococcal strains in vitro studied 13 were highly sensitive to 0.1 mug/ml and 28 were resistant to 100 mug/ml or more of clindamycin-2-phosphate. 2. In experiments with rabbits, clindamycin-2-phosphate showed superior penetration into the ocular tissues after intravenous injection than after intramuscular injection. 3. Clindamycin-2-phosphate was administered intramuscularly at the dose of 300 mg to 6 healthy volunteers. The blood concentrations of 6 cases averaged 3.2 mug/ml after 1 hour, and 0.8 mug/ml after 6 hours. 4. Fourteen patients with extraocular infection were treated with daily intramuscular administration of 300 mg of clindamycin-2-phosphate. All of them improved by the treatment, and no side effect was observed."}
{"id": "PMID:14270", "title": "Experimental models for prevention of graft-versus-host reaction in bone marrow transfusion. I. Selective suppression and augmentation of splenomegaly and cytotoxicity.", "content": "Induction and suppression of splenomegaly and cytotoxicity against C57BL/L cells were studied in (AKR X C57BL/6) F1 hybrid adult mice after the transfer of AKR lymphoid and bone marrow cells. 1) Splenomegaly and cytotoxicity were dissociated in the developmental stages of the graft-versus-host reaction. When lymphoid and bone marrow cells of normal AKR mice were injected into F1 recipients, splenomegaly was prominent on days 5 and 7, but cytotoxicity of spleen cells was not detected. Splenomegaly became less prominent but the cytotoxicity became detectable on day 14 after the injection. 2) Cytotoxic activity of spleen cells of F1 recipients was suppressed by the treatment of AKR donors with C57BL/6 lymphoid cells in Freund's complete adjuvant. Splenomegaly, however, was substantially enhanced by such a treatment of the donors. On the other hand, induction of the cytotoxic activity was facilitated by the treatment of donors with C57BL/6 skin grafts. 3) F1 hybrid mice could be protected from the graft-versus-host reaction by the injection of AKR anti-C57BL/6 serum or pretreatment of AKR donors with sonicated cellular antigens of C57BL/6.", "contents": "Experimental models for prevention of graft-versus-host reaction in bone marrow transfusion. I. Selective suppression and augmentation of splenomegaly and cytotoxicity. Induction and suppression of splenomegaly and cytotoxicity against C57BL/L cells were studied in (AKR X C57BL/6) F1 hybrid adult mice after the transfer of AKR lymphoid and bone marrow cells. 1) Splenomegaly and cytotoxicity were dissociated in the developmental stages of the graft-versus-host reaction. When lymphoid and bone marrow cells of normal AKR mice were injected into F1 recipients, splenomegaly was prominent on days 5 and 7, but cytotoxicity of spleen cells was not detected. Splenomegaly became less prominent but the cytotoxicity became detectable on day 14 after the injection. 2) Cytotoxic activity of spleen cells of F1 recipients was suppressed by the treatment of AKR donors with C57BL/6 lymphoid cells in Freund's complete adjuvant. Splenomegaly, however, was substantially enhanced by such a treatment of the donors. On the other hand, induction of the cytotoxic activity was facilitated by the treatment of donors with C57BL/6 skin grafts. 3) F1 hybrid mice could be protected from the graft-versus-host reaction by the injection of AKR anti-C57BL/6 serum or pretreatment of AKR donors with sonicated cellular antigens of C57BL/6."}
{"id": "PMID:14271", "title": "Germination of unactivated spores of Bacillus cereus T. Effect of preincubation with L-alanine or inosine on the subsequent germination.", "content": "Heat-activated spores of Bacillus cereus T germinate rapidly in the presence of L-alanine alone or inosine alone. In contrast, unactivated spores can not germinate in the presence of either germinant alone but rapidly in the presence of both germinants. The highest level of cooperative action of L-alanine and inosine on the germination was observed when they were present in a ratio 1:1. Preincubations of unactivated spores with L-alanine or inosine had opposite effects on the subsequent germination in the presence of both germinants: preincubation with L-alanine stimulated the initiation of subsequent germination, while preincubation with inosine inhibited it. These results suggest that germination of unactivated spores initiated by L-alanine and inosine includes two steps, the first initiated by L-alanine and the second prompted by inosine. The effect of preincubation of unactivated spores with L-alanine was not diminished by washings. The pH dependence of the preincubation of unactivated spores was not so marked as that of the subsequent germination in the presence of inosine.", "contents": "Germination of unactivated spores of Bacillus cereus T. Effect of preincubation with L-alanine or inosine on the subsequent germination. Heat-activated spores of Bacillus cereus T germinate rapidly in the presence of L-alanine alone or inosine alone. In contrast, unactivated spores can not germinate in the presence of either germinant alone but rapidly in the presence of both germinants. The highest level of cooperative action of L-alanine and inosine on the germination was observed when they were present in a ratio 1:1. Preincubations of unactivated spores with L-alanine or inosine had opposite effects on the subsequent germination in the presence of both germinants: preincubation with L-alanine stimulated the initiation of subsequent germination, while preincubation with inosine inhibited it. These results suggest that germination of unactivated spores initiated by L-alanine and inosine includes two steps, the first initiated by L-alanine and the second prompted by inosine. The effect of preincubation of unactivated spores with L-alanine was not diminished by washings. The pH dependence of the preincubation of unactivated spores was not so marked as that of the subsequent germination in the presence of inosine."}
{"id": "PMID:14273", "title": "Iron poisoning.", "content": "Based on the metabolism, pathophysiology and clinical picture of iron poisoning, a treatment protocol for the emergency department is presented. For insignificant amounts, treatment is ipecac and oral bicarbonate. For ingestions of amounts greater than 150 mg/kg, even if the patient is asymptomatic, hospital observation is necessary. Chelation therapy with Desferal is reserved for patients with free serum iron, and probably for patients who present in coma, shock, or convulsions.", "contents": "Iron poisoning. Based on the metabolism, pathophysiology and clinical picture of iron poisoning, a treatment protocol for the emergency department is presented. For insignificant amounts, treatment is ipecac and oral bicarbonate. For ingestions of amounts greater than 150 mg/kg, even if the patient is asymptomatic, hospital observation is necessary. Chelation therapy with Desferal is reserved for patients with free serum iron, and probably for patients who present in coma, shock, or convulsions."}
{"id": "PMID:14275", "title": "[Bone marrow transplanation by aplastic anemia and acute leukemia--chances, success, indications (author's transl)].", "content": "The experimental background, methods of preventing immunological complications and clinical results of bone marrow transplantation in cases with aplastic anemia and acute leukemia in relapse are reported. The causes for failure in clinical bone marrow transplantation insert: are discussed. The possibilities of bone marrow transplantation appear superior to conventional therapeutic measures, if a histocompatible sibling donor is available.", "contents": "[Bone marrow transplanation by aplastic anemia and acute leukemia--chances, success, indications (author's transl)]. The experimental background, methods of preventing immunological complications and clinical results of bone marrow transplantation in cases with aplastic anemia and acute leukemia in relapse are reported. The causes for failure in clinical bone marrow transplantation insert: are discussed. The possibilities of bone marrow transplantation appear superior to conventional therapeutic measures, if a histocompatible sibling donor is available."}
{"id": "PMID:14276", "title": "[Long space flights and the human habitat].", "content": "The paper discusses the generation of an environment which may adequately meet human requirements that have developed as a result of evolution in the Earth biosphere as applied to long-duration manned space flights. This environment must exert functional effects on physiological systems of the human body which appear to be underloaded in space flight.", "contents": "[Long space flights and the human habitat]. The paper discusses the generation of an environment which may adequately meet human requirements that have developed as a result of evolution in the Earth biosphere as applied to long-duration manned space flights. This environment must exert functional effects on physiological systems of the human body which appear to be underloaded in space flight."}
{"id": "PMID:14279", "title": "Otitis media of guinea pigs.", "content": "Otitis media occurred in 177 of 1373 guinea pigs necropsied during a six-year period. Streptococcus pneumoniae (20%), Streptococcus zooepidemicus (15%), Bordetella bronchiseptica (12%), and Pseudomonas aeruginosa (11%) were the most common bacteria isolated from affected tympanic bullae. Radiology and otoscopy were tested as means of antemortem screening for affected guinea pigs. Radiology gave 96% accuracy in diagnosing otitis media and proved to be a more satisfactory technique than otoscopy.", "contents": "Otitis media of guinea pigs. Otitis media occurred in 177 of 1373 guinea pigs necropsied during a six-year period. Streptococcus pneumoniae (20%), Streptococcus zooepidemicus (15%), Bordetella bronchiseptica (12%), and Pseudomonas aeruginosa (11%) were the most common bacteria isolated from affected tympanic bullae. Radiology and otoscopy were tested as means of antemortem screening for affected guinea pigs. Radiology gave 96% accuracy in diagnosing otitis media and proved to be a more satisfactory technique than otoscopy."}
{"id": "PMID:14277", "title": "[Patterns in the change in the body state of dogs during a breakdown of the atmosphere regeneration system in a pressurized space].", "content": "Experiments were carried out on dogs kept in a sealed chamber. Changes in the O2 and CO2 concentrations as well as variations of physiological functions, the so-called survival curves, were studied under the conditions of terminated O2 supply and CO2 utilization. The criteria of investigation, mathematical and physiological analysis were chosen from the point of view of predicting hazardous states during failures of the environmental control system. Tolerance limits during slow and rapid changes of the environment, phases of changes of the body state and mechanisms of a combined effect of increasing hypercapnia and hypoxia were considered.", "contents": "[Patterns in the change in the body state of dogs during a breakdown of the atmosphere regeneration system in a pressurized space]. Experiments were carried out on dogs kept in a sealed chamber. Changes in the O2 and CO2 concentrations as well as variations of physiological functions, the so-called survival curves, were studied under the conditions of terminated O2 supply and CO2 utilization. The criteria of investigation, mathematical and physiological analysis were chosen from the point of view of predicting hazardous states during failures of the environmental control system. Tolerance limits during slow and rapid changes of the environment, phases of changes of the body state and mechanisms of a combined effect of increasing hypercapnia and hypoxia were considered."}
{"id": "PMID:14282", "title": "Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism.", "content": "Ventricular fibrillation is frequently induced during cardiac surgery to quiet the operative field. The reported effects of fibrillation on the myocardium vary considerably. In an attempt to better define these effects, we subjected 28 dogs to one hour of total normothermic bypass. Myocardial blood flow, lactate, adenosine triphosphate (ATP), oxygen consumption, and left ventricular fibrillation was induced in 5 dogs and continuous electrical fibrillation in 7 dogs. These groups were compared to two respective control groups with beating hearts of 8 animals each. Coronary sinus flow, total coronary blood flow, left ventricular flow, myocardial oxygen consumption, and myocardial tissue lactate increased significantly in the fibrillating hearts. Left ventricular dp/dt decreased with fibrillation, but not significantly. It is concluded that the metabolic demands of ventricular fibrillation exceed the increase in coronary blood flow, when compared to demands of the beating heart, and that decreased left ventricular performance may result.", "contents": "Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism. Ventricular fibrillation is frequently induced during cardiac surgery to quiet the operative field. The reported effects of fibrillation on the myocardium vary considerably. In an attempt to better define these effects, we subjected 28 dogs to one hour of total normothermic bypass. Myocardial blood flow, lactate, adenosine triphosphate (ATP), oxygen consumption, and left ventricular fibrillation was induced in 5 dogs and continuous electrical fibrillation in 7 dogs. These groups were compared to two respective control groups with beating hearts of 8 animals each. Coronary sinus flow, total coronary blood flow, left ventricular flow, myocardial oxygen consumption, and myocardial tissue lactate increased significantly in the fibrillating hearts. Left ventricular dp/dt decreased with fibrillation, but not significantly. It is concluded that the metabolic demands of ventricular fibrillation exceed the increase in coronary blood flow, when compared to demands of the beating heart, and that decreased left ventricular performance may result."}
{"id": "PMID:14295", "title": "Arterialized capillary blood gases in exercise studies.", "content": "The PCO2, PO2 and pH of arterial blood and arterialized capillary blood from the ear lobe were compared in 13 patients at rest and during submaximal exercise. The mean capillary PCO2 was .6 mmHg lower than arterial PCO2 at rest and 1 mmHg lower in exercise. The variation in comparisons (S.D. 1.4 mmHg) at rest and exercise, was greater than between duplicate capillary samples (S.D. .7 mmHg). The mean capillary PO2 was 3.3 mmHg higher than arterial at rest, and 1.7 mmHg higher in exercise: the variation was also greater than for PCO2 (S.D. 5.2 MMHg at rest, 4.2 mmHg in exercise) and greater than in duplicate samples (S.D. 2.6 mmHg). A comparison was made of calculated cardiac output (indirect Fick method) and dead space: tidal volume ratio during exercise, using arterial PCO2 and capillary PCO2: cardiac output was systematically overestimated by 6% (S.D. 9.3%) and VD/VT ratio underestimated by 10% (S.D. 9-3%) when capillary PCO2 was used in the calculations. Capillary blood samples are an acceptable alternative to arterial blood, for measurement of blood gases and pH, as long as blood flow is brisk enough to fill a large (125 mgl) glass capillary tube within 30 seconds. The accuracy of the estimates is greatest for pH, and least for PO2. The PCO2 and PO2 measurements are sufficiently precise for their use in the calculation of cardiac output, VD/VT ratio, alveolar-arterial PO2 difference and venous admixture effect during exercise.", "contents": "Arterialized capillary blood gases in exercise studies. The PCO2, PO2 and pH of arterial blood and arterialized capillary blood from the ear lobe were compared in 13 patients at rest and during submaximal exercise. The mean capillary PCO2 was .6 mmHg lower than arterial PCO2 at rest and 1 mmHg lower in exercise. The variation in comparisons (S.D. 1.4 mmHg) at rest and exercise, was greater than between duplicate capillary samples (S.D. .7 mmHg). The mean capillary PO2 was 3.3 mmHg higher than arterial at rest, and 1.7 mmHg higher in exercise: the variation was also greater than for PCO2 (S.D. 5.2 MMHg at rest, 4.2 mmHg in exercise) and greater than in duplicate samples (S.D. 2.6 mmHg). A comparison was made of calculated cardiac output (indirect Fick method) and dead space: tidal volume ratio during exercise, using arterial PCO2 and capillary PCO2: cardiac output was systematically overestimated by 6% (S.D. 9.3%) and VD/VT ratio underestimated by 10% (S.D. 9-3%) when capillary PCO2 was used in the calculations. Capillary blood samples are an acceptable alternative to arterial blood, for measurement of blood gases and pH, as long as blood flow is brisk enough to fill a large (125 mgl) glass capillary tube within 30 seconds. The accuracy of the estimates is greatest for pH, and least for PO2. The PCO2 and PO2 measurements are sufficiently precise for their use in the calculation of cardiac output, VD/VT ratio, alveolar-arterial PO2 difference and venous admixture effect during exercise."}
{"id": "PMID:14297", "title": "[Intragastric titration with extragastric pH-metry--a clinically applicable and reliable technique of quantitative analysis of gastric secretion (author's transl)].", "content": "A technique is described by which the secretory capacity of the stomach can be determined. It appears to be superior both to intragastric titration along with intragastric pH-metry and to common analysis of gastric juice obtained by aspiration. There is no essential difference when comparing results obtained intraindividually by intragastric titration with the pH being measured either inside or outside the stomach. When titrating intragastricly with the pH being measured extragastricly, a tube is used which can be check more easily, remains usable much longer, and - as a result of its smaller diameter - is tolerated much better by the patient. In contrast to common analysis of gastric juice obtained by aspiration, by intragastric titration with the pH being measured extragastricly gastric acid can be determined at its site of production (less volume loss and rediffusion of H+ -ions into tissue), the results obtained representing more accurately the true secretory capacity of the stomach. As can be seen from its results, the technique presented here is apt particularly to both testing antacids and the substances interfering with gastric secretion; it also appears to be superior to common analysis of gastric juice obtained by aspiration.", "contents": "[Intragastric titration with extragastric pH-metry--a clinically applicable and reliable technique of quantitative analysis of gastric secretion (author's transl)]. A technique is described by which the secretory capacity of the stomach can be determined. It appears to be superior both to intragastric titration along with intragastric pH-metry and to common analysis of gastric juice obtained by aspiration. There is no essential difference when comparing results obtained intraindividually by intragastric titration with the pH being measured either inside or outside the stomach. When titrating intragastricly with the pH being measured extragastricly, a tube is used which can be check more easily, remains usable much longer, and - as a result of its smaller diameter - is tolerated much better by the patient. In contrast to common analysis of gastric juice obtained by aspiration, by intragastric titration with the pH being measured extragastricly gastric acid can be determined at its site of production (less volume loss and rediffusion of H+ -ions into tissue), the results obtained representing more accurately the true secretory capacity of the stomach. As can be seen from its results, the technique presented here is apt particularly to both testing antacids and the substances interfering with gastric secretion; it also appears to be superior to common analysis of gastric juice obtained by aspiration."}
{"id": "PMID:14294", "title": "The Asian species of strychnos. Part IV. The alkaloids.", "content": "Two hundred thirty-four samples from thirty-six Asian species of Strychnos have been screened for the presence of tertiary alkaloids; the data are set out in table 1. Thin-layer and gas-liquid chromatographic as well as mass-spectrometric studies have enabled alkaloids to be identified in many of the extracts prepared; the data are listed in table 2. The literature on the alkaloids and pharmacology of Asian Strychnos species is reviewed (altogether 99 plant names are considered) and compared with the findings obtained in the present work. The alkaloid economy of the plants is also discussed.", "contents": "The Asian species of strychnos. Part IV. The alkaloids. Two hundred thirty-four samples from thirty-six Asian species of Strychnos have been screened for the presence of tertiary alkaloids; the data are set out in table 1. Thin-layer and gas-liquid chromatographic as well as mass-spectrometric studies have enabled alkaloids to be identified in many of the extracts prepared; the data are listed in table 2. The literature on the alkaloids and pharmacology of Asian Strychnos species is reviewed (altogether 99 plant names are considered) and compared with the findings obtained in the present work. The alkaloid economy of the plants is also discussed."}
{"id": "PMID:14299", "title": "[Spermatogonia counts in descended and undescended prebuberal testes (author's transl)].", "content": "The following conclusions which show the importance of time of medical treatment resulted from the examination of 288 testicular biopsies (including 46 controls) by statistical analysis in correlation to age. 1. There is no difference in the number of spermatogonia per tubule cross section of descended and undescended testes in children from birth to 2 years of age. 2. The number of spermtogonia in descended testes is not different in children from birth to 2 years in comparison to children aged 2-6 years. 3. A statistically significant decrease of spermatogonia takes place in the undescended testes of children from 2-6 years in comparison to children from birth to 2 years. 4. The difference in the number of spermatogonia of descended and undescended testes increases in children above the age of 2. It must be concluded from this study that the pathological alterations of the germinative epithelium increase in children beyond the age of 2. Assuming that pathological alterations of the germinative epithelium are caused by the dystopy of the testes, medical treatment should be carried out before the child is more than 2 years old.", "contents": "[Spermatogonia counts in descended and undescended prebuberal testes (author's transl)]. The following conclusions which show the importance of time of medical treatment resulted from the examination of 288 testicular biopsies (including 46 controls) by statistical analysis in correlation to age. 1. There is no difference in the number of spermatogonia per tubule cross section of descended and undescended testes in children from birth to 2 years of age. 2. The number of spermtogonia in descended testes is not different in children from birth to 2 years in comparison to children aged 2-6 years. 3. A statistically significant decrease of spermatogonia takes place in the undescended testes of children from 2-6 years in comparison to children from birth to 2 years. 4. The difference in the number of spermatogonia of descended and undescended testes increases in children above the age of 2. It must be concluded from this study that the pathological alterations of the germinative epithelium increase in children beyond the age of 2. Assuming that pathological alterations of the germinative epithelium are caused by the dystopy of the testes, medical treatment should be carried out before the child is more than 2 years old."}
{"id": "PMID:14303", "title": "[Chemical modification of proteins. 2. Blocking of amino groups and basic amino acids and crosslinking of polypeptide chains in casein and field bean globulin by reaction with dialdehyde starch].", "content": "The reaction of dialdehyde starch with casein and field-bean globulin leads to a blocking of the protein amino groups and to a decrease of free lysine, arginine and histidine. Maximum values are reached at high protein concentrations and great molar reagent excess. At best 80-93% of the amino groups or of the available lysine may be blocked in this way. For 1% casein and I and 5% globulin solutions, the pH optimum of the reaction lies at approximately 8; for 5% casein solutions, it is shifted towards the neutral to weakly acidic range. The value for the proportion of unblocked lysine is higher (approximately 5%) when determined by amino-acid analysis after acid total hydrolysis than when measured by means of the colorimetric method according to Carpenter (20%). The difference is designed as reversibly blocked lysine proportion. There is a linear correlation between the proportion of blocked lysine and the relative nutritional value as determined by means of the test organism Tetrahymena pyriformis. Dependently on protein concentration and reagent excess, gel chromatographically detectable cross-linking products of higher molecular weight are formed by the reaction of dialdehyde starch with casein. In 5% protein solutions, such products with molecular weights of less than or equal to 900 000 are the sole detectable components.", "contents": "[Chemical modification of proteins. 2. Blocking of amino groups and basic amino acids and crosslinking of polypeptide chains in casein and field bean globulin by reaction with dialdehyde starch]. The reaction of dialdehyde starch with casein and field-bean globulin leads to a blocking of the protein amino groups and to a decrease of free lysine, arginine and histidine. Maximum values are reached at high protein concentrations and great molar reagent excess. At best 80-93% of the amino groups or of the available lysine may be blocked in this way. For 1% casein and I and 5% globulin solutions, the pH optimum of the reaction lies at approximately 8; for 5% casein solutions, it is shifted towards the neutral to weakly acidic range. The value for the proportion of unblocked lysine is higher (approximately 5%) when determined by amino-acid analysis after acid total hydrolysis than when measured by means of the colorimetric method according to Carpenter (20%). The difference is designed as reversibly blocked lysine proportion. There is a linear correlation between the proportion of blocked lysine and the relative nutritional value as determined by means of the test organism Tetrahymena pyriformis. Dependently on protein concentration and reagent excess, gel chromatographically detectable cross-linking products of higher molecular weight are formed by the reaction of dialdehyde starch with casein. In 5% protein solutions, such products with molecular weights of less than or equal to 900 000 are the sole detectable components."}
{"id": "PMID:14304", "title": "Signs, symptoms, and pathophysiology of Pneumocystis carinii pneumonitis.", "content": "In 80 patients with Pneumocystis pneumonitis, the intial signs and symptoms of infection were usually fever and cough, followed by tachypnea and coryza. Flaring of the nasal alae and cyanosis occurred later. Blood gas composition was markedly altered in its acid-base profile in most patients at admission. There was moderate to severe respiratory alkalosis and hypoxia. Clinical manifestations were correlated with the extent of histopathologic changes in the lung. (Deprivation of protein in the diet of rats provoked P. carinii infection.) P. carinii infection was found in children with kwashiorkor; evidence of protein-calorie malnutrition is closely associated with P. carinii pneumonitis in children wiht cancer and other primary diseases. P. carinii pneumonitis proved unique in that the causative organisms remained limited to the lungs even in fatal cases. No toxins have been identified, and systemic effects of the infection were only those that could be related to hypoxia and fever.", "contents": "Signs, symptoms, and pathophysiology of Pneumocystis carinii pneumonitis. In 80 patients with Pneumocystis pneumonitis, the intial signs and symptoms of infection were usually fever and cough, followed by tachypnea and coryza. Flaring of the nasal alae and cyanosis occurred later. Blood gas composition was markedly altered in its acid-base profile in most patients at admission. There was moderate to severe respiratory alkalosis and hypoxia. Clinical manifestations were correlated with the extent of histopathologic changes in the lung. (Deprivation of protein in the diet of rats provoked P. carinii infection.) P. carinii infection was found in children with kwashiorkor; evidence of protein-calorie malnutrition is closely associated with P. carinii pneumonitis in children wiht cancer and other primary diseases. P. carinii pneumonitis proved unique in that the causative organisms remained limited to the lungs even in fatal cases. No toxins have been identified, and systemic effects of the infection were only those that could be related to hypoxia and fever."}
{"id": "PMID:14305", "title": "Relaxation of heart muscle by catecholamines and by dibutyryl cyclic adenosine 3',5'-monophosphate. Similarity of beta-adrenoceptors mediating contractile and relaxant effects of catecholamines in kitten pipillary muscle.", "content": "1. In isometrically contracting kitten papillary muscles, dibutyryl cyclic AMP (DBcAMP) enhanced peak tension, increased rates of contraction and relaxation, decreased tension of a phasic but not of a small tonic component of KCl-contractures, and caused aftercontractions. These effects resemble closely those of catecholamines. 2. The effects of DBcAMP on kitten papillary muscle were not influenced by (-)-bupranolol, a beta-adrenoceptor antagonist. 3. DBcAMP decreased KCl-contractures in strips of frog ventricle. 4. Phasic KCl-contractures in kitten papillary muscles were decreased by (-)- and (+)-isoprenaline. For similar effects, 100-fold higher concentrations of (+)-isoprenaline than of (-)-isoprenaline were required. 5. Increases in maximum rates of contraction and relaxation, increases in peak tension of isometric contractions and reduction of phasic KCl-contractures by catecholamines were antagonized competitively to a similar extent by (-)-bupranolol. Mean apparent equilibrium constants for the beta-adrenoceptor-(-)-bupranolol complex of 0.46-0.70 nM were estimated. These constants were quite similar irrespective of whether (-)-isoprenaline, (+)-isoprenaline or (-)-noradrenaline were used as agonists. 6. Increases in contractile strength, maximum rates of contraction and of relaxation of isometric contractions and decreases in KCl-contractures by (-)-isoprenaline were surmountably blocked by (+)-bupranolol. Mean apparent equilibrium constants for the receptor-(+)-bupranolol complex were 40-50 nM. 7. The equilibrium constants of (-)- and (+)-bupranolol for the receptors mediating positive inotropic and relaxant effects of catecholamines were not significantly different from constants for bupranolol-receptor complexes in cell-free membrane particles of kitten heart ventricle. It is suggested that the same beta-adrenoceptor triggers positive inotropic, relaxant and adenylyl cyclase-activating effects of catecholamines in kitten papillary muscle. 8. The partial agonist (-)-dichloroisoprenaline (DCI) (1 muM) reduced by 79% the phasic KCl-contractures of the kitten papillary muscles. DCI stimulates adenylyl cyclase activity of ventricle membranes to less than 1/4 of maximum stimulation by (-)-isoprenaline. If cyclic AMP produced by DCI is involved in the decrease of phasic KCl-contracture, small increase in cyclic AMP should be sufficient to induce this effect.", "contents": "Relaxation of heart muscle by catecholamines and by dibutyryl cyclic adenosine 3',5'-monophosphate. Similarity of beta-adrenoceptors mediating contractile and relaxant effects of catecholamines in kitten pipillary muscle. 1. In isometrically contracting kitten papillary muscles, dibutyryl cyclic AMP (DBcAMP) enhanced peak tension, increased rates of contraction and relaxation, decreased tension of a phasic but not of a small tonic component of KCl-contractures, and caused aftercontractions. These effects resemble closely those of catecholamines. 2. The effects of DBcAMP on kitten papillary muscle were not influenced by (-)-bupranolol, a beta-adrenoceptor antagonist. 3. DBcAMP decreased KCl-contractures in strips of frog ventricle. 4. Phasic KCl-contractures in kitten papillary muscles were decreased by (-)- and (+)-isoprenaline. For similar effects, 100-fold higher concentrations of (+)-isoprenaline than of (-)-isoprenaline were required. 5. Increases in maximum rates of contraction and relaxation, increases in peak tension of isometric contractions and reduction of phasic KCl-contractures by catecholamines were antagonized competitively to a similar extent by (-)-bupranolol. Mean apparent equilibrium constants for the beta-adrenoceptor-(-)-bupranolol complex of 0.46-0.70 nM were estimated. These constants were quite similar irrespective of whether (-)-isoprenaline, (+)-isoprenaline or (-)-noradrenaline were used as agonists. 6. Increases in contractile strength, maximum rates of contraction and of relaxation of isometric contractions and decreases in KCl-contractures by (-)-isoprenaline were surmountably blocked by (+)-bupranolol. Mean apparent equilibrium constants for the receptor-(+)-bupranolol complex were 40-50 nM. 7. The equilibrium constants of (-)- and (+)-bupranolol for the receptors mediating positive inotropic and relaxant effects of catecholamines were not significantly different from constants for bupranolol-receptor complexes in cell-free membrane particles of kitten heart ventricle. It is suggested that the same beta-adrenoceptor triggers positive inotropic, relaxant and adenylyl cyclase-activating effects of catecholamines in kitten papillary muscle. 8. The partial agonist (-)-dichloroisoprenaline (DCI) (1 muM) reduced by 79% the phasic KCl-contractures of the kitten papillary muscles. DCI stimulates adenylyl cyclase activity of ventricle membranes to less than 1/4 of maximum stimulation by (-)-isoprenaline. If cyclic AMP produced by DCI is involved in the decrease of phasic KCl-contracture, small increase in cyclic AMP should be sufficient to induce this effect."}
{"id": "PMID:14306", "title": "Activation of myocardial beta-adrenoceptors by the nitrogen-free low affinity ligand 3',4'-dihydroxy-alpha-methylpropiophenone (U-0521).", "content": "The effect of 3',4'-dihydroxy-alpha-methylpropiophenone (U-0521) on the rate of spontaneously contracting cultured rat heart cells and right atria of rats and kittens was investigated. The action of U-0521 on the cellular content of cyclic AMP and on the adenylyl cyclase of heart membrane particels was also studied. 1. U-0521 caused positive chronotropic effects on single cultured heart cells and right atria of the rat. U-0521 was about 10(5) times less potent than (--)-isoprenaline. The maximum effect of U-0521 was smaller than the maximum effect of (--)-isoprenaline. A small positive chronotropic effect of U-0521 was also observed on kitten atria. 2. The beta-adrenoceptor blocker (--)-bupranolol antagonized the positive chronotropic effects of U-0521 to the same extent as the effects of (--)-isoprenaline on single cells and atria of the rat. The effects of both U-0521 and (--)-isoprenaline appear therefore mediated through the same beta-adrenoceptors. The positive chronotropic effects of U-0521 on kitten atria were also blocked by (--)-bupranolol. 3. Up to 0.1 mM U-0521 did not block the effects of (--)-isoprenaline on rat atria, not even in the presence of corticosterone or hydrocortisone. 4. 1 min incubations with equieffective (increase in cellular beating rate) concentrations of U-0521 (0.1 mM) and (--)-isoprenaline (1 nM) caused a significant increase in the cellular content of cAMP; this effect of both drugs was antagonized by 10 nM (--)-bupranolol. 5. 0.1--3.3 mM U-0521 did not stimulate the adenylyl cyclase of cell-free membrane particles of kitten ventricles. The cyclase was depressed by 10 mM U-0521. 3.3 mM U-0521 caused a 20% decrease of the maximum cyclase-stimulating effect of (--)-isoprenaline and a 1.6-fold increase of its apparent Km. 6. The results with U-0521 suggest that beta-adrenoceptors can be activated by agonists devoid of nitrogen. However, the affinity of U-0521 for the beta-adrenoceptor is very low (KU-0521 approximately 5.5 mM). The concentration of U-0521 (0.1 mM) causing maximal increases in beating rate of cultured cells probably occupies less than 7% of the available beta-adrenoceptors.", "contents": "Activation of myocardial beta-adrenoceptors by the nitrogen-free low affinity ligand 3',4'-dihydroxy-alpha-methylpropiophenone (U-0521). The effect of 3',4'-dihydroxy-alpha-methylpropiophenone (U-0521) on the rate of spontaneously contracting cultured rat heart cells and right atria of rats and kittens was investigated. The action of U-0521 on the cellular content of cyclic AMP and on the adenylyl cyclase of heart membrane particels was also studied. 1. U-0521 caused positive chronotropic effects on single cultured heart cells and right atria of the rat. U-0521 was about 10(5) times less potent than (--)-isoprenaline. The maximum effect of U-0521 was smaller than the maximum effect of (--)-isoprenaline. A small positive chronotropic effect of U-0521 was also observed on kitten atria. 2. The beta-adrenoceptor blocker (--)-bupranolol antagonized the positive chronotropic effects of U-0521 to the same extent as the effects of (--)-isoprenaline on single cells and atria of the rat. The effects of both U-0521 and (--)-isoprenaline appear therefore mediated through the same beta-adrenoceptors. The positive chronotropic effects of U-0521 on kitten atria were also blocked by (--)-bupranolol. 3. Up to 0.1 mM U-0521 did not block the effects of (--)-isoprenaline on rat atria, not even in the presence of corticosterone or hydrocortisone. 4. 1 min incubations with equieffective (increase in cellular beating rate) concentrations of U-0521 (0.1 mM) and (--)-isoprenaline (1 nM) caused a significant increase in the cellular content of cAMP; this effect of both drugs was antagonized by 10 nM (--)-bupranolol. 5. 0.1--3.3 mM U-0521 did not stimulate the adenylyl cyclase of cell-free membrane particles of kitten ventricles. The cyclase was depressed by 10 mM U-0521. 3.3 mM U-0521 caused a 20% decrease of the maximum cyclase-stimulating effect of (--)-isoprenaline and a 1.6-fold increase of its apparent Km. 6. The results with U-0521 suggest that beta-adrenoceptors can be activated by agonists devoid of nitrogen. However, the affinity of U-0521 for the beta-adrenoceptor is very low (KU-0521 approximately 5.5 mM). The concentration of U-0521 (0.1 mM) causing maximal increases in beating rate of cultured cells probably occupies less than 7% of the available beta-adrenoceptors."}
{"id": "PMID:14307", "title": "Central sites and mechanisms of the hypotensive and bradycardic effects of the narcotic analgesic agent fentanyl.", "content": "In dogs, anaesthetized with chloralose, fentanyl (5 mug/kg i.v.) augmented the bradycardia produced by electrical stimulation of the carotid sinus nerves. In contrast, the same dose of the drug did not change the bradycardic response to stimulation of the nucleus of the solitary tract (NTS) indicating that a central facilitation of baroreceptor impulses occurs within the NTS, probably at the first synapse of baroreceptor reflex fibres. Bilateral destruction of the NTS caused a fulminating hypertension and tachycardia similar to that after cutting the baroreceptor afferent fibres. After both procedures, fentanyl (20 mug/kg i.v.) produced marked hypotension and bradycardia. The bradycardic effect was abolished by cutting both vagal nerves when the dogs were pretreated with a beta-adrenoceptor blocking agent (S 2395, 50 mug/kg i.v.). The results provide evidence that the NTS is not the main site of action either for the hypotensive effect or for the vagally mediated bradycardia of fentanyl. Since the dorsal nucleus of the vagal nerve was destroyed together with the NTS, this nucleus does also not appear to be a major site of the action of fentanyl. Blockade of dopamine receptors by haloperidol or pimozide or of serotonin receptors by methysergide did not change the hypotensive, bradycardic and sympathoinhibitory effects of fentanyl.", "contents": "Central sites and mechanisms of the hypotensive and bradycardic effects of the narcotic analgesic agent fentanyl. In dogs, anaesthetized with chloralose, fentanyl (5 mug/kg i.v.) augmented the bradycardia produced by electrical stimulation of the carotid sinus nerves. In contrast, the same dose of the drug did not change the bradycardic response to stimulation of the nucleus of the solitary tract (NTS) indicating that a central facilitation of baroreceptor impulses occurs within the NTS, probably at the first synapse of baroreceptor reflex fibres. Bilateral destruction of the NTS caused a fulminating hypertension and tachycardia similar to that after cutting the baroreceptor afferent fibres. After both procedures, fentanyl (20 mug/kg i.v.) produced marked hypotension and bradycardia. The bradycardic effect was abolished by cutting both vagal nerves when the dogs were pretreated with a beta-adrenoceptor blocking agent (S 2395, 50 mug/kg i.v.). The results provide evidence that the NTS is not the main site of action either for the hypotensive effect or for the vagally mediated bradycardia of fentanyl. Since the dorsal nucleus of the vagal nerve was destroyed together with the NTS, this nucleus does also not appear to be a major site of the action of fentanyl. Blockade of dopamine receptors by haloperidol or pimozide or of serotonin receptors by methysergide did not change the hypotensive, bradycardic and sympathoinhibitory effects of fentanyl."}
{"id": "PMID:14308", "title": "The in vitro secretion of epidermal growth factor by mouse submandibular salivary gland.", "content": "A technique for the study of epidermal growth factor (EGF) secretion from salivary gland pieces in vitro is described and the responses to a variety of drugs are compared to the results of previously reported in vivo studies. Adrenaline stimulates secretion of the growth factor as does the alpha-adrenergic agonist phenylephrine, while isoprenaline is less active in stimulating EGF secretion. Phentolamine, but not propranolol, blocks the secretory activity of adrenaline and isoprenaline in this system. Pretreatment of the salivary gland pieces with colchicine reduces the secretory response to adrenaline, suggesting an involvement of microtubular proteins in the process. It is anticipated that the in vitro technique described will provide a means by which detailed investigation of the secretion of epidermal growth factor can be made.", "contents": "The in vitro secretion of epidermal growth factor by mouse submandibular salivary gland. A technique for the study of epidermal growth factor (EGF) secretion from salivary gland pieces in vitro is described and the responses to a variety of drugs are compared to the results of previously reported in vivo studies. Adrenaline stimulates secretion of the growth factor as does the alpha-adrenergic agonist phenylephrine, while isoprenaline is less active in stimulating EGF secretion. Phentolamine, but not propranolol, blocks the secretory activity of adrenaline and isoprenaline in this system. Pretreatment of the salivary gland pieces with colchicine reduces the secretory response to adrenaline, suggesting an involvement of microtubular proteins in the process. It is anticipated that the in vitro technique described will provide a means by which detailed investigation of the secretion of epidermal growth factor can be made."}
{"id": "PMID:14309", "title": "Effect of passages of Morris hepatoma 5123D in F1 (Buffalo X Wistar) rats on permanent decrease of gamma-glutamyltranspeptidase activity.", "content": "The Morris hepatoma 5123D after at least two passages in F1 (Buffalo X Wistar) rats shows quicker growth than the original tumor and bearers of it have much lower gamma-glutamyltranspeptidase activity in serum, urine, tumor and in some other organs. This new variant of the hepatoma was labeled as hepatoma 5123D/AS. Simultaneous implantation of hepatomas 5123D/AS and 5123D in the same rats prevents the increase of serum gamma-glutamyltranspeptidase activity. After surgical removal of the former tumor, the enzyme activity in serum quickly increases. No significant differences in some other peptidase activities were observed between the variant and hepatoma 5123D.", "contents": "Effect of passages of Morris hepatoma 5123D in F1 (Buffalo X Wistar) rats on permanent decrease of gamma-glutamyltranspeptidase activity. The Morris hepatoma 5123D after at least two passages in F1 (Buffalo X Wistar) rats shows quicker growth than the original tumor and bearers of it have much lower gamma-glutamyltranspeptidase activity in serum, urine, tumor and in some other organs. This new variant of the hepatoma was labeled as hepatoma 5123D/AS. Simultaneous implantation of hepatomas 5123D/AS and 5123D in the same rats prevents the increase of serum gamma-glutamyltranspeptidase activity. After surgical removal of the former tumor, the enzyme activity in serum quickly increases. No significant differences in some other peptidase activities were observed between the variant and hepatoma 5123D."}
{"id": "PMID:14311", "title": "[Dynamics of synaptic changes in experimental audiogenic epilepsy].", "content": "The dynamics of ultrastructural changes in axonal endings were studied after experimental epileptic seizures. Mice and rats from strains with genetically--determined audiogenic epilepsy were used as a model of epilepsy. The animals were divided into 3 groups: in group 1 only one seizure was evoked, in group 2 eight seizures within 4 hours, group 3 served as control. The animals were killed immediately after the last seizure, 30 min. after it or 1 hour after the seizure. Hippocampal gyrus cortex was impregnated with zinc-iodide-osmium tetroxide and synapses were examined under electron microscope. The number of synaptic vesicles showing positive reaction with zinc iodide was calculated in 20 synaptic boutons in each group. A significant correlation was demonstrated between the frequency of seizures and the survival time after the seizure on the one hand, and synaptic changes, on the other. In the control group 97% of synaptic vesicles were filled with neurotransmitter substance giving positive reaction with zinc iodide. Immediately after the single seizure 46% of synaptic vesicles were found emptied, 30 min. later the neurotransmitter substance was demonstrated in 79% of vesicles, 1 hour later 82% of vesicles had normal appearance. Immediately after serial seizures 91% of vesicles were found empty, 30 min. later the neurotransmitter was present in 50% of vesicles, 1 hour later in 78%. In another group of animals seizures were evoked once daily for 40 days (chronic epilepsy model). Synaptic changes were different: the synaptic boutons were swollen, the number of vesicles was reduced, greatly enlarged vesicles and clear membrane-bound vacuoles appeared. They evidenced degenerative character of changes. It is suggested that degenerative synaptic changes may be a substrate of epileptic dementia.", "contents": "[Dynamics of synaptic changes in experimental audiogenic epilepsy]. The dynamics of ultrastructural changes in axonal endings were studied after experimental epileptic seizures. Mice and rats from strains with genetically--determined audiogenic epilepsy were used as a model of epilepsy. The animals were divided into 3 groups: in group 1 only one seizure was evoked, in group 2 eight seizures within 4 hours, group 3 served as control. The animals were killed immediately after the last seizure, 30 min. after it or 1 hour after the seizure. Hippocampal gyrus cortex was impregnated with zinc-iodide-osmium tetroxide and synapses were examined under electron microscope. The number of synaptic vesicles showing positive reaction with zinc iodide was calculated in 20 synaptic boutons in each group. A significant correlation was demonstrated between the frequency of seizures and the survival time after the seizure on the one hand, and synaptic changes, on the other. In the control group 97% of synaptic vesicles were filled with neurotransmitter substance giving positive reaction with zinc iodide. Immediately after the single seizure 46% of synaptic vesicles were found emptied, 30 min. later the neurotransmitter substance was demonstrated in 79% of vesicles, 1 hour later 82% of vesicles had normal appearance. Immediately after serial seizures 91% of vesicles were found empty, 30 min. later the neurotransmitter was present in 50% of vesicles, 1 hour later in 78%. In another group of animals seizures were evoked once daily for 40 days (chronic epilepsy model). Synaptic changes were different: the synaptic boutons were swollen, the number of vesicles was reduced, greatly enlarged vesicles and clear membrane-bound vacuoles appeared. They evidenced degenerative character of changes. It is suggested that degenerative synaptic changes may be a substrate of epileptic dementia."}
{"id": "PMID:14317", "title": "[New preparation with antalgic sedative and anxiolytic activity in manifestations of interest to internal medicine. Double-blind controlled clinical study].", "content": "A controlled double-blind clinical trial using randomised blocks was carried out on 3 groups of 10 patients with internal diseases and a pain syndrome accompanied by anxiety. One group received the product under examination (FC 35aA) and the other two its components (dipotassic chlorazepate, paracetamol and codeine). FC 35aA gave the best results, pointing to synergism between its components. Increase of the pain threshold and of the actual involvement of the patient was achieved to an extent that the single components could not match when administered individually at the same doses.", "contents": "[New preparation with antalgic sedative and anxiolytic activity in manifestations of interest to internal medicine. Double-blind controlled clinical study]. A controlled double-blind clinical trial using randomised blocks was carried out on 3 groups of 10 patients with internal diseases and a pain syndrome accompanied by anxiety. One group received the product under examination (FC 35aA) and the other two its components (dipotassic chlorazepate, paracetamol and codeine). FC 35aA gave the best results, pointing to synergism between its components. Increase of the pain threshold and of the actual involvement of the patient was achieved to an extent that the single components could not match when administered individually at the same doses."}
{"id": "PMID:14320", "title": "Some studies in an institution for the mentally retarded.", "content": "Patient characteristics and psychotropic drug use in a hospital for the mentally retarded were studied. The majority of patients appeared permanent, 80 percent having been there five years. Ages ranged from 2 to 71 years. Most were mildly or moderately retarded. Fifty-five percent had been originally domiciled within two hours driving time of the hospital. Visiting was proportional to time in hospital, degree of retardation and distance of domicile from hospital. Forty percent of patients were on some kind of psychotropic medication for behavioural control, the majority of these receiving two or more antipsychotic drugs in moderate dosage (phenothiazines or butyrophenones). Despite their long acting nature, drugs were given several times a day. Average time on present medication was about one year. A subgroup of patients was taken off medication and observed by staff. Almost all deteriorated behaviourally but the study was not double blind so these findings must be treated with caution.", "contents": "Some studies in an institution for the mentally retarded. Patient characteristics and psychotropic drug use in a hospital for the mentally retarded were studied. The majority of patients appeared permanent, 80 percent having been there five years. Ages ranged from 2 to 71 years. Most were mildly or moderately retarded. Fifty-five percent had been originally domiciled within two hours driving time of the hospital. Visiting was proportional to time in hospital, degree of retardation and distance of domicile from hospital. Forty percent of patients were on some kind of psychotropic medication for behavioural control, the majority of these receiving two or more antipsychotic drugs in moderate dosage (phenothiazines or butyrophenones). Despite their long acting nature, drugs were given several times a day. Average time on present medication was about one year. A subgroup of patients was taken off medication and observed by staff. Almost all deteriorated behaviourally but the study was not double blind so these findings must be treated with caution."}
{"id": "PMID:14321", "title": "New Zealand Committee on Adverse Drug Reactions: eleventh annual report 1976.", "content": "Under the voluntary reporting scheme 499 cases of adverse drug reaction or reactions were reported. Noteworthy items included immediate hypersensitivity-type reactions to anaesthetic agents, a number of life-threatening reactions to anti-inflammatory drugs, paradoxical increase in blood pressure with high-dose pindolol and rebound hypertension after cessation of clonidine. A further 904 reactions were reported during an intensive survey in general practice and 342 from the ongoing hospital monitoring studies in units at the Auckland and Hutt hospitals. Data from numerous sources are now being channelled through the Committee's administrative centre. During the 11th year of operations 499 reports were received under the spontaneous reporting scheme. Additionally 342 reactions derived from the established hospital monitoring programmes at the Auckland Hospital and School of Medicine and the Hutt Hospital were notified to the Committee, and a further 904 reactions were received as a result of the intensive monitoring survey of drug reactions in general practice carried out in October and November 1975. The significance of each of these sets of data is substantially different and they will be discussed separately.", "contents": "New Zealand Committee on Adverse Drug Reactions: eleventh annual report 1976. Under the voluntary reporting scheme 499 cases of adverse drug reaction or reactions were reported. Noteworthy items included immediate hypersensitivity-type reactions to anaesthetic agents, a number of life-threatening reactions to anti-inflammatory drugs, paradoxical increase in blood pressure with high-dose pindolol and rebound hypertension after cessation of clonidine. A further 904 reactions were reported during an intensive survey in general practice and 342 from the ongoing hospital monitoring studies in units at the Auckland and Hutt hospitals. Data from numerous sources are now being channelled through the Committee's administrative centre. During the 11th year of operations 499 reports were received under the spontaneous reporting scheme. Additionally 342 reactions derived from the established hospital monitoring programmes at the Auckland Hospital and School of Medicine and the Hutt Hospital were notified to the Committee, and a further 904 reactions were received as a result of the intensive monitoring survey of drug reactions in general practice carried out in October and November 1975. The significance of each of these sets of data is substantially different and they will be discussed separately."}
{"id": "PMID:14324", "title": "Flight muscle ultrastructure of susceptible and refractory mosquitoes parasitized by larval Brugia pahangi.", "content": "On parasitization with larval Brugia pahangi the infected flight muscle fibres of \"resistant\" Anopheles labranchiae atroparvus undergo the following ultrastructural changes. The fibres become almost totally devoid of glycogen, their sarcoplasmic reticulum becomes elongate and closely associated with muscle fibrils. These fibrils degenerate and vesicles appear both within the degenerate fibril and within elements of the sarcoplasmic reticulum. Vesicles accumulate around the worm and degenerate to a uniform mass which eventually becomes melanized from its inner edge (next to the parasite) outwards. The infected flight muscle fibres of both \"resistant\" Aedes aegypti and \"susceptible\" Aedes togoi are almost totally devoid of glycogen granules, but show no other ultrastructural change from the uninfected state.", "contents": "Flight muscle ultrastructure of susceptible and refractory mosquitoes parasitized by larval Brugia pahangi. On parasitization with larval Brugia pahangi the infected flight muscle fibres of \"resistant\" Anopheles labranchiae atroparvus undergo the following ultrastructural changes. The fibres become almost totally devoid of glycogen, their sarcoplasmic reticulum becomes elongate and closely associated with muscle fibrils. These fibrils degenerate and vesicles appear both within the degenerate fibril and within elements of the sarcoplasmic reticulum. Vesicles accumulate around the worm and degenerate to a uniform mass which eventually becomes melanized from its inner edge (next to the parasite) outwards. The infected flight muscle fibres of both \"resistant\" Aedes aegypti and \"susceptible\" Aedes togoi are almost totally devoid of glycogen granules, but show no other ultrastructural change from the uninfected state."}
{"id": "PMID:14326", "title": "Multiple leukocyte abnormalities in chronic granulomatous disease: a familial study.", "content": "A variety of leukocyte enzyme activities were studied in an 11-year-old female with chronic granulomatous disease (CGD) and several members of her family. Leukocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity was 17 nmol/min/mg protein in the patient; two brothers with symptoms of recurrent bacterial infections have G-6-PD activities of 58 and 37 nmol/min/mg protein; the activites of this enzyme in both parents, maternal grandmother, and one additional brother were within normal limits. Storage at 4 degrees or heating at 37 degrees over a 120-min period revealed a marked lability of G-6-PD activity in the patient's cells which could not be stabilized by the addition of NADP and 2-mercaptoethanol; this lability was not seen in other family members tested. Activities of leukocyte glutathione reductase were reduced in both parents and the two affected male siblings with values of 18, 23, 23, and 24 nmol/min/mg protein, respectively. Activities of leukocyte glutathione peroxidase were reduced in all of the immediate family members tested, with values ranging from 11.2 to 43 nmol/min/mg protein; the activity of this enzyme in the patient was 38.5. Leukocyte NADP content in the patient, father, and two affected male siblings were 16.5, 23.4, 22.2, and 28.2 nmol/15 min/10(7) leukocytes, respectively.", "contents": "Multiple leukocyte abnormalities in chronic granulomatous disease: a familial study. A variety of leukocyte enzyme activities were studied in an 11-year-old female with chronic granulomatous disease (CGD) and several members of her family. Leukocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity was 17 nmol/min/mg protein in the patient; two brothers with symptoms of recurrent bacterial infections have G-6-PD activities of 58 and 37 nmol/min/mg protein; the activites of this enzyme in both parents, maternal grandmother, and one additional brother were within normal limits. Storage at 4 degrees or heating at 37 degrees over a 120-min period revealed a marked lability of G-6-PD activity in the patient's cells which could not be stabilized by the addition of NADP and 2-mercaptoethanol; this lability was not seen in other family members tested. Activities of leukocyte glutathione reductase were reduced in both parents and the two affected male siblings with values of 18, 23, 23, and 24 nmol/min/mg protein, respectively. Activities of leukocyte glutathione peroxidase were reduced in all of the immediate family members tested, with values ranging from 11.2 to 43 nmol/min/mg protein; the activity of this enzyme in the patient was 38.5. Leukocyte NADP content in the patient, father, and two affected male siblings were 16.5, 23.4, 22.2, and 28.2 nmol/15 min/10(7) leukocytes, respectively."}
{"id": "PMID:14327", "title": "Fluoresceinylthiocarbamyl-tRNATyr: a useful derivative of tRNATyr (E.coli) for physicochemical studies.", "content": "Fluoresceinylthiocarbamyl-tRNATyr (FTC-tRNATyr) is prepared from tRNATyr and fluoresceinisothiogyanate (FITC) under mildly alkaline conditions. Labelling occurs specificly at the base Q of tRNATyr. The modified tRNA is fully active in the aminoacylation assay; when aminoacylated it is recognized by the elongation factor Tu (EF-Tu). Codon-anticodon interaction, however, is severely affected by the modification.", "contents": "Fluoresceinylthiocarbamyl-tRNATyr: a useful derivative of tRNATyr (E.coli) for physicochemical studies. Fluoresceinylthiocarbamyl-tRNATyr (FTC-tRNATyr) is prepared from tRNATyr and fluoresceinisothiogyanate (FITC) under mildly alkaline conditions. Labelling occurs specificly at the base Q of tRNATyr. The modified tRNA is fully active in the aminoacylation assay; when aminoacylated it is recognized by the elongation factor Tu (EF-Tu). Codon-anticodon interaction, however, is severely affected by the modification."}
{"id": "PMID:14323", "title": "[Perspectives of use of genetic methods of control of bloodsucking Diptera - vectors of the diseases of man].", "content": "This paper presents genetic methods of control of bloodsucking Diptera, mosquitoes. The perspective of the use of various control methods, first of all those tested under field conditions in application for bloodsuckers which are of medical importance throughout the USSR, is regarded. The opinion is suggested that the method of X-ray sterilization of pupae taken from nature and the translocation and chemical sterilization methods can be successfully used for the control of An. m. sacharovi, malaria vectors resistant to DDT. The male sterilization method and the use of males cytoplasmatically incompatible with translocations are suggested for the control of synanthropic populations of C. pipiens.", "contents": "[Perspectives of use of genetic methods of control of bloodsucking Diptera - vectors of the diseases of man]. This paper presents genetic methods of control of bloodsucking Diptera, mosquitoes. The perspective of the use of various control methods, first of all those tested under field conditions in application for bloodsuckers which are of medical importance throughout the USSR, is regarded. The opinion is suggested that the method of X-ray sterilization of pupae taken from nature and the translocation and chemical sterilization methods can be successfully used for the control of An. m. sacharovi, malaria vectors resistant to DDT. The male sterilization method and the use of males cytoplasmatically incompatible with translocations are suggested for the control of synanthropic populations of C. pipiens."}
{"id": "PMID:14328", "title": "A 31P-NMR study of the interaction of Mg2+ ions with nucleoside diphosphates.", "content": "The interaction of Mg2+ with nucleoside disphosphates : ADP, GDP, CDP and UDP has been studied by phosphorus magnetic resonance spectroscopy in aqueous solution. The results show that these four nucleotides behave similarly, the Mg2+ ion binds to the alpha but not to the beta phosphate moiety. The strength of the interaction of Mg2+ ions with nucleoside diphosphates is weaker than with nucleoside triphosphates. The association of Mg2+ on the phosphate chain is stronger in a neutral than in an acid medium.", "contents": "A 31P-NMR study of the interaction of Mg2+ ions with nucleoside diphosphates. The interaction of Mg2+ with nucleoside disphosphates : ADP, GDP, CDP and UDP has been studied by phosphorus magnetic resonance spectroscopy in aqueous solution. The results show that these four nucleotides behave similarly, the Mg2+ ion binds to the alpha but not to the beta phosphate moiety. The strength of the interaction of Mg2+ ions with nucleoside diphosphates is weaker than with nucleoside triphosphates. The association of Mg2+ on the phosphate chain is stronger in a neutral than in an acid medium."}
{"id": "PMID:14332", "title": "High-dose treatment with neuroleptics in the acute phase of mental disease.", "content": "More than 300 patients have been observed during treatment with either flupenthixol, haloperidol, fluphenazine enanthate or perphenazine enanthate in high doses, whilst suffering from severe mental disease, usually of psychotic nature. Used correctly, high-dose treatment gives a rapid control of psychotic symptoms, an earlier discharge from the ward, and (when using long-acting neuroleptics) pharmacological control even during a follow up period. This means a social availability gain of 30-50%. We have not seen any severe somatic effects except those of parkinsonian type which can be treated successfully by the well trained psychiatrist and a skilled staff.", "contents": "High-dose treatment with neuroleptics in the acute phase of mental disease. More than 300 patients have been observed during treatment with either flupenthixol, haloperidol, fluphenazine enanthate or perphenazine enanthate in high doses, whilst suffering from severe mental disease, usually of psychotic nature. Used correctly, high-dose treatment gives a rapid control of psychotic symptoms, an earlier discharge from the ward, and (when using long-acting neuroleptics) pharmacological control even during a follow up period. This means a social availability gain of 30-50%. We have not seen any severe somatic effects except those of parkinsonian type which can be treated successfully by the well trained psychiatrist and a skilled staff."}
{"id": "PMID:14338", "title": "Competitive inhibitors of renin. A review.", "content": "This review describes some of the characteristics for renin's substrate specificity and also some features of its species specificity. It describes how competitive inhibitors were synthesized and how the solubility was increased in order to make them effective at physiological pH. Their use for in vitro and in vivo inhibition of renin is discussed and their use for purification of renin demonstrated.", "contents": "Competitive inhibitors of renin. A review. This review describes some of the characteristics for renin's substrate specificity and also some features of its species specificity. It describes how competitive inhibitors were synthesized and how the solubility was increased in order to make them effective at physiological pH. Their use for in vitro and in vivo inhibition of renin is discussed and their use for purification of renin demonstrated."}
{"id": "PMID:14340", "title": "Interaction of salicylic acid with adenosine and adenosine triphosphate. Potential mechanism of intensifying acetylsalicylic acid-induced GI blood loss.", "content": "Complex formation between salicylic acid and adenosine or adenosine triphosphate in 0.2m phosphate buffer at pH=7 was investigated as a potential factor contributing to the prolongation of acetylsalicylic acid-induced GI blood loss. Spectrophotemetric techniques were used to evalute the complexation. Concerntration dependency of the absorbance decrease was measured at 27 and 37 degrees C. The addition of salicylic acid to either adenosine or adenosine triphosplate solutions appeared also to cause a decrease in surface tension which may play a role in reducing platelet aggregation induced by adenosine diphosphate. The results obtained seem to support the opinion that the mechansim of acetylsalicylic acid-induced GI blood loss is due to a combination of both local and systemic effect.", "contents": "Interaction of salicylic acid with adenosine and adenosine triphosphate. Potential mechanism of intensifying acetylsalicylic acid-induced GI blood loss. Complex formation between salicylic acid and adenosine or adenosine triphosphate in 0.2m phosphate buffer at pH=7 was investigated as a potential factor contributing to the prolongation of acetylsalicylic acid-induced GI blood loss. Spectrophotemetric techniques were used to evalute the complexation. Concerntration dependency of the absorbance decrease was measured at 27 and 37 degrees C. The addition of salicylic acid to either adenosine or adenosine triphosplate solutions appeared also to cause a decrease in surface tension which may play a role in reducing platelet aggregation induced by adenosine diphosphate. The results obtained seem to support the opinion that the mechansim of acetylsalicylic acid-induced GI blood loss is due to a combination of both local and systemic effect."}
{"id": "PMID:14342", "title": "Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 3: Kinetics of solvolysis of major intermediates of 5.5-diallylbarbituric acid degradation.", "content": "Solvolysis of N-diallylacetylurea and 5.5-diallylmalonuric acid was investigated in the pH range ca. 8--12 by means of spectrophotometric and t.l.c. methods. Their log k--pH profiles were constructed from the experimental results obtained by degradation at 70 degrees C. Therefore, specific catalytic rate constants and pKa's were derived. The kinetic mechanism of N-diallylacetylurea solvolysis, resulting among other things from the so-called kinetic salt effect, depends on hydroxyl-ion attack on its undissociated and monoanionic forms. However, the degradation of alpha.alpha-diallylmalonuric acid in the pH range 10--12 is an example of specific base catalysis which can be explained by hydroxyl-ion attack on its monoanionic species. The degradation of alpha.alpha-diallylmalonuric acid below pH=10 does not follow a theoretical equation postulated, because the spectrophotometric method does not allow monitoring the formation of N-diallylacetylurea in the presence of the above acid. Thin-layer chromatography was used to check different pathways of transformations of the intermediate studies.", "contents": "Kinetics and mechanism of degradation of some 5-allylbarbituric acid derivatives. Part 3: Kinetics of solvolysis of major intermediates of 5.5-diallylbarbituric acid degradation. Solvolysis of N-diallylacetylurea and 5.5-diallylmalonuric acid was investigated in the pH range ca. 8--12 by means of spectrophotometric and t.l.c. methods. Their log k--pH profiles were constructed from the experimental results obtained by degradation at 70 degrees C. Therefore, specific catalytic rate constants and pKa's were derived. The kinetic mechanism of N-diallylacetylurea solvolysis, resulting among other things from the so-called kinetic salt effect, depends on hydroxyl-ion attack on its undissociated and monoanionic forms. However, the degradation of alpha.alpha-diallylmalonuric acid in the pH range 10--12 is an example of specific base catalysis which can be explained by hydroxyl-ion attack on its monoanionic species. The degradation of alpha.alpha-diallylmalonuric acid below pH=10 does not follow a theoretical equation postulated, because the spectrophotometric method does not allow monitoring the formation of N-diallylacetylurea in the presence of the above acid. Thin-layer chromatography was used to check different pathways of transformations of the intermediate studies."}
{"id": "PMID:14346", "title": "Effects of hypolipidemic agents on lipid synthesis in subcellular fractions from Tetrahymena pyriformis.", "content": "Lipid synthesizing systems have been prepared from subcellular fractions of Tetrahymena pyriformis, GL. These fractions, the mitochondrial fraction, the microsomal fraction and the soluble cell fraction, have been characterized as to cofactors and cations required for optimal lipid synthesis. The effects of hypolipidemic agents on lipid synthesis by all fractions are presented.", "contents": "Effects of hypolipidemic agents on lipid synthesis in subcellular fractions from Tetrahymena pyriformis. Lipid synthesizing systems have been prepared from subcellular fractions of Tetrahymena pyriformis, GL. These fractions, the mitochondrial fraction, the microsomal fraction and the soluble cell fraction, have been characterized as to cofactors and cations required for optimal lipid synthesis. The effects of hypolipidemic agents on lipid synthesis by all fractions are presented."}
{"id": "PMID:14347", "title": "Analgesic, heart rate, and temperature effects of delta8-THC during acute and chronic administration to conscious rats.", "content": "Acute and chronic effects of delta8-THC on tail-flick, heart rate, and rectal temperature responses in conscious, unrestrained male rats were studied. In the acute experiment unidirectional dose-dependent analgesic, hypothermic, and negative chronotropic cardiac effects were observed within the dose range employed. Of the three variables, heart-rate decreases were most sensitive to the effects of THC, reaching significance at 2 mg/kg. Rapid development of tolerance occurred for all three measures, with complete tolerance developing within 13 days only to the heart-rate decreases. The results discussed in the context of previous data.", "contents": "Analgesic, heart rate, and temperature effects of delta8-THC during acute and chronic administration to conscious rats. Acute and chronic effects of delta8-THC on tail-flick, heart rate, and rectal temperature responses in conscious, unrestrained male rats were studied. In the acute experiment unidirectional dose-dependent analgesic, hypothermic, and negative chronotropic cardiac effects were observed within the dose range employed. Of the three variables, heart-rate decreases were most sensitive to the effects of THC, reaching significance at 2 mg/kg. Rapid development of tolerance occurred for all three measures, with complete tolerance developing within 13 days only to the heart-rate decreases. The results discussed in the context of previous data."}
{"id": "PMID:14350", "title": "Efficacy of loxapine in the treatment of paranoid schizophrenia.", "content": "A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia (5 studies) and chronic schizophrenia (6 studies) showed statistically significant superiority of loxapine on several items and factors of standardized psychiatric rating scales. Upon review of these findings, it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could, in the main, be considered a broad paranoid \"cluster\". The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia, paranoid type and in those patients of any diagnostic subtype other than paranoid. Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients; nonparanoid patients responded at least equally as well to loxapine as to the reference compounds. Findings could not be attributed to inadequate dosages of the references compounds or inequality of treatment groups at baseline.", "contents": "Efficacy of loxapine in the treatment of paranoid schizophrenia. A combined analysis of data from 11 controlled studies of loxapine versus either chlorpromazine or trifluoperazine in acute schizophrenia (5 studies) and chronic schizophrenia (6 studies) showed statistically significant superiority of loxapine on several items and factors of standardized psychiatric rating scales. Upon review of these findings, it was observed that the rating scale symptoms for which loxapine appeared superior to the reference compounds could, in the main, be considered a broad paranoid \"cluster\". The data were then reanalyzed to detect possible differences in efficacy of loxapine versus the reference compounds in those patients with a clinical diagnosis of schizophrenia, paranoid type and in those patients of any diagnostic subtype other than paranoid. Results of these analyses demonstrated clear superiority of loxapine in paranoid schizophrenic patients; nonparanoid patients responded at least equally as well to loxapine as to the reference compounds. Findings could not be attributed to inadequate dosages of the references compounds or inequality of treatment groups at baseline."}
{"id": "PMID:14351", "title": "[Psychopharmacological influence on the prey catching behavior of ferrets (Putorius furo L.) (author's transl)].", "content": "The prey-catching behavior of ferrets (Putorius furo L.) consists mainly of instinctive behavior patterns, which can be elicited only through their releaser. Then they are performed stereotypically. To get information concerning the central background and the hierarchical structure of this behavior the neuroleptics Haloperidol (0.14 mg/kg), Clozapine (10 mg/kg) and Chlorpromazine (4 mg/kg) were injected i.m. under controlled conditions. In a conditioning experiment the reactivity of the animals was examined. This conditioned reaction was strongly decreased by the drugs. The reaction to the natural stimulus the prey was changed, but not suppressed. The modification of the predatory behavior was manifedsted in an \"improvement\" of orientation reactions when pursuing the prey and in a better placement of bites. This effect, most evident with Haloperidol, is possibly due to the specific neuroleptic component of the substances. A delay in approaching the prey, or even the total suppression of the prey-catching behavior is suggested to be due to a sedative component which was most obvious in some experiments with Clozapine. On the other hand, there are behavioral elements like the use of paws which are not effected by the neuroleptics. From these and other observations, it is concluded, that the predatory behavior of the ferret has a hierarchically organisated structure. Further it is suggested that some functional connected parts of the behavior have distinct central representation, for they are not influenced in the same way by these drugs.", "contents": "[Psychopharmacological influence on the prey catching behavior of ferrets (Putorius furo L.) (author's transl)]. The prey-catching behavior of ferrets (Putorius furo L.) consists mainly of instinctive behavior patterns, which can be elicited only through their releaser. Then they are performed stereotypically. To get information concerning the central background and the hierarchical structure of this behavior the neuroleptics Haloperidol (0.14 mg/kg), Clozapine (10 mg/kg) and Chlorpromazine (4 mg/kg) were injected i.m. under controlled conditions. In a conditioning experiment the reactivity of the animals was examined. This conditioned reaction was strongly decreased by the drugs. The reaction to the natural stimulus the prey was changed, but not suppressed. The modification of the predatory behavior was manifedsted in an \"improvement\" of orientation reactions when pursuing the prey and in a better placement of bites. This effect, most evident with Haloperidol, is possibly due to the specific neuroleptic component of the substances. A delay in approaching the prey, or even the total suppression of the prey-catching behavior is suggested to be due to a sedative component which was most obvious in some experiments with Clozapine. On the other hand, there are behavioral elements like the use of paws which are not effected by the neuroleptics. From these and other observations, it is concluded, that the predatory behavior of the ferret has a hierarchically organisated structure. Further it is suggested that some functional connected parts of the behavior have distinct central representation, for they are not influenced in the same way by these drugs."}
{"id": "PMID:14352", "title": "Effect of flupenthixol and butaclamol isomers on prolactin secretion in rats.", "content": "Cis (alpha)-flupenthixol and (+)-butaclamol are effective anti-psychotic agents but trans (beta)-flupenthixol and (-)-butaclamol are not. alpha-Flupenthixol was found to be 245 times more active in elevating rat plasma prolactin than the beta-isomer. The discrepancy between (+)-butaclamol and (-)-butaclamol was even greater. These results support the hypothesis that the dopamine receptors that mediate the effects of dopamine on prolactin secretion are similar to those that mediate the anti-psychotic effect of neuroleptic drugs.", "contents": "Effect of flupenthixol and butaclamol isomers on prolactin secretion in rats. Cis (alpha)-flupenthixol and (+)-butaclamol are effective anti-psychotic agents but trans (beta)-flupenthixol and (-)-butaclamol are not. alpha-Flupenthixol was found to be 245 times more active in elevating rat plasma prolactin than the beta-isomer. The discrepancy between (+)-butaclamol and (-)-butaclamol was even greater. These results support the hypothesis that the dopamine receptors that mediate the effects of dopamine on prolactin secretion are similar to those that mediate the anti-psychotic effect of neuroleptic drugs."}
{"id": "PMID:14353", "title": "Changes in dopamine synthesis rate in the supersensitivity phase after treatment with a single dose of neuroleptics.", "content": "The changes in 14C-dopamine accumulation formed from 14C-tyrosine in mice after treatment with three neuroleptics, cis (Z)-flupenthixol, fluphenazine, and haloperidol, were followed for 6 days. The neuroleptics all changed DA synthesis rate in the same way, initially causing an increase which was followed by a decrease after approximately 3 days. The results are compared with pharmacological results (Christensen et al., 1976) and there seems to be a very close correlation between receptor blockade and increase in DA synthesis on the one hand and on the other hand receptor supersensitivity and decrease in DA synthesis, as was also shown previously for teflutixol (Hyttel, 1975). It is concluded that the changes in receptor activity are always followed by compensatory changes in DA synthesis rate.", "contents": "Changes in dopamine synthesis rate in the supersensitivity phase after treatment with a single dose of neuroleptics. The changes in 14C-dopamine accumulation formed from 14C-tyrosine in mice after treatment with three neuroleptics, cis (Z)-flupenthixol, fluphenazine, and haloperidol, were followed for 6 days. The neuroleptics all changed DA synthesis rate in the same way, initially causing an increase which was followed by a decrease after approximately 3 days. The results are compared with pharmacological results (Christensen et al., 1976) and there seems to be a very close correlation between receptor blockade and increase in DA synthesis on the one hand and on the other hand receptor supersensitivity and decrease in DA synthesis, as was also shown previously for teflutixol (Hyttel, 1975). It is concluded that the changes in receptor activity are always followed by compensatory changes in DA synthesis rate."}
{"id": "PMID:14361", "title": "The biosynthesis of dimethyltryptamine in vivo.", "content": "The in vivo formation of dimethyltryptamine was studied in rabbits, rats and monkeys. When C14-labelled N-methyltryptamine was administered by intravenous injection to rabbits, C14-dimethyltryptamine was found in lung, the principle site of the methyltransferase that biosynthesizes this psychotogen. Unequivocal evidence for C14-dimethyltryptamine formation in rat tissues was not obtained. When rabbits were given non-radioactive N-methyltryptamine intravenously, dimethyltryptamine appeared in carotid arterail blood, peaking within the first minute after injection of the precursor. USing this assay procedure we could not demonstrate dimethyltryptamine synthesis in the rhesus monkey.", "contents": "The biosynthesis of dimethyltryptamine in vivo. The in vivo formation of dimethyltryptamine was studied in rabbits, rats and monkeys. When C14-labelled N-methyltryptamine was administered by intravenous injection to rabbits, C14-dimethyltryptamine was found in lung, the principle site of the methyltransferase that biosynthesizes this psychotogen. Unequivocal evidence for C14-dimethyltryptamine formation in rat tissues was not obtained. When rabbits were given non-radioactive N-methyltryptamine intravenously, dimethyltryptamine appeared in carotid arterail blood, peaking within the first minute after injection of the precursor. USing this assay procedure we could not demonstrate dimethyltryptamine synthesis in the rhesus monkey."}
{"id": "PMID:14362", "title": "An improved technique for the preparation of chromosomes from cattle whole blood.", "content": "The method of preparation of chromosomes from cattle whole blood is described in detail and has been tested by use on more than 1000 different animal samples. It is shown that elevated levels of glutamine and 1-cystine increase the mitotic index and improve the keeping qualities of the medium 199. The recipe for whole medium is modified, describing the inclusion of heparin for the first time and recommending the exclusion of fetal calf serum. The optimum pH 7-3 is confirmed. The reported conditions of transport show that the best results pertain where air transport is used and the worst after prolonged journeys by car.", "contents": "An improved technique for the preparation of chromosomes from cattle whole blood. The method of preparation of chromosomes from cattle whole blood is described in detail and has been tested by use on more than 1000 different animal samples. It is shown that elevated levels of glutamine and 1-cystine increase the mitotic index and improve the keeping qualities of the medium 199. The recipe for whole medium is modified, describing the inclusion of heparin for the first time and recommending the exclusion of fetal calf serum. The optimum pH 7-3 is confirmed. The reported conditions of transport show that the best results pertain where air transport is used and the worst after prolonged journeys by car."}
{"id": "PMID:14363", "title": "Blood respiratory properties in the naked mole rat Heterocephalus glaber, a mammal of low body temperature.", "content": "Respiratory properties of whole blood and Hb solutions have been studied in Heterocephalus glaber, a fossorial rodent, having a low body temperature (30.0-32.0 degrees C) and poor thermoregulatory ability. For comparison similar, measurements were made on laboratory mice, Mus musculus. Whole blood showed a distinctly higher O2 affinity for Heterocephalus at both 30 and 37 degrees C.P50 values were 23.3 mm Hg and 33.0 mm Hg at 37 degrees C for Heterocephalus and Mus, respectively, while at 30 degrees CP50's were 18.8 mm Hg and 24.9 mm Hg, all values at pH (b) 7.4. deltaH values (expressive of the effect of temperature on P50) were -5.8 kcal-mol-1 for Heterocephalus and -7.5 kcal-mol-1 for Mus. The CO2 Bohr effects (omega) were -0.43 and -0.50 for Heterocephalus at 37 and 30 degrees C. Corresponding values for Mus were -0.65 and -0.56. Both species had a Hill's n-value of 2.6. Red cell concentrations of 2,3-DGP were closely similar in the species being 7.3 mmol-L-1 rbc for Heterocephalus and 7.4 mmol-L-1 rbc for Mus. Stripped Heterocephalus Hb had a very high O2 affinity, at pH 7.25, 37 degrees C,P50 was 8.0 mm Hg whereas the corresponding value for Mus was 11.3 mm Hg. Addition of DPG to stripped Hb from the two species decreased O2 affinity to the same degree. The high O2 affinity of Heterocephalus blood is viewed as a possible adaptation to its burrowing habits. Its basis is inherent to the hemoglobin molecule itself and not dependent upon cofactor influence or the temperature sensitivity of the O2-Hb binding.", "contents": "Blood respiratory properties in the naked mole rat Heterocephalus glaber, a mammal of low body temperature. Respiratory properties of whole blood and Hb solutions have been studied in Heterocephalus glaber, a fossorial rodent, having a low body temperature (30.0-32.0 degrees C) and poor thermoregulatory ability. For comparison similar, measurements were made on laboratory mice, Mus musculus. Whole blood showed a distinctly higher O2 affinity for Heterocephalus at both 30 and 37 degrees C.P50 values were 23.3 mm Hg and 33.0 mm Hg at 37 degrees C for Heterocephalus and Mus, respectively, while at 30 degrees CP50's were 18.8 mm Hg and 24.9 mm Hg, all values at pH (b) 7.4. deltaH values (expressive of the effect of temperature on P50) were -5.8 kcal-mol-1 for Heterocephalus and -7.5 kcal-mol-1 for Mus. The CO2 Bohr effects (omega) were -0.43 and -0.50 for Heterocephalus at 37 and 30 degrees C. Corresponding values for Mus were -0.65 and -0.56. Both species had a Hill's n-value of 2.6. Red cell concentrations of 2,3-DGP were closely similar in the species being 7.3 mmol-L-1 rbc for Heterocephalus and 7.4 mmol-L-1 rbc for Mus. Stripped Heterocephalus Hb had a very high O2 affinity, at pH 7.25, 37 degrees C,P50 was 8.0 mm Hg whereas the corresponding value for Mus was 11.3 mm Hg. Addition of DPG to stripped Hb from the two species decreased O2 affinity to the same degree. The high O2 affinity of Heterocephalus blood is viewed as a possible adaptation to its burrowing habits. Its basis is inherent to the hemoglobin molecule itself and not dependent upon cofactor influence or the temperature sensitivity of the O2-Hb binding."}
{"id": "PMID:14364", "title": "The role of brief hypocapnia in the ventilatory response to CO2 with hypoxia.", "content": "In conscious cats the ventilatory response curve to physiological range of CO2 is displaced upward by hypoxia (about 45 torr), but it rises, either parallel with, or convergent on, the normoxic curve. Thus, a positive interaction of hypoxia and hypercapnic stimuli is not observed under these circumstances. However, if during the hypoxic exposure, hypocapnia is allowed to develop, the subsequently determined CO2 ventilatory response curve will shift to the left, rise steeply, particularly in the early phase, and demonstrate a positive hypoxic hypercapnic interaction. A demonstrable interactive effect was dependent on a conditioning period of hypocapnia, and this was shown to be associated with an elevated level of lactic acid to a greater degree in cerebral venous blood than in CSF or arterial blood. The interpretation is discussed without reaching a firm conclusion of mechanism, but the results emphasize how a minor change of experimental protocol affects a basic phenomenon in the chemical control of breathing.", "contents": "The role of brief hypocapnia in the ventilatory response to CO2 with hypoxia. In conscious cats the ventilatory response curve to physiological range of CO2 is displaced upward by hypoxia (about 45 torr), but it rises, either parallel with, or convergent on, the normoxic curve. Thus, a positive interaction of hypoxia and hypercapnic stimuli is not observed under these circumstances. However, if during the hypoxic exposure, hypocapnia is allowed to develop, the subsequently determined CO2 ventilatory response curve will shift to the left, rise steeply, particularly in the early phase, and demonstrate a positive hypoxic hypercapnic interaction. A demonstrable interactive effect was dependent on a conditioning period of hypocapnia, and this was shown to be associated with an elevated level of lactic acid to a greater degree in cerebral venous blood than in CSF or arterial blood. The interpretation is discussed without reaching a firm conclusion of mechanism, but the results emphasize how a minor change of experimental protocol affects a basic phenomenon in the chemical control of breathing."}
{"id": "PMID:14365", "title": "Ventilatory and circulatory O2 convection at 4000 m in pigeon at neutral or cold temperature.", "content": "Awake domestic pigeons, either maintained at 22 degrees C (series I) or acutely exposed at 2 degrees C (series II), were studied in a hypobaric chamber at 140 m and at various stages during a 4-week exposure to 4000 m. Steady-state pulmonary ventilation (Vg) and breathing pattern (VT, fr), oxygen consumption (MO2), O2 concentrations and pressures in the arterial (a) and mixed venous blood (v), hematocrit (Ht) and acid-base status in arterial blood, systolic blood pressure and heart frequency (fH) were measured. From these data cardiac output (Vb) and stroke volume (Vs), ventilatory and circulatory requirements (Vg/MO2, Vb/MO2), extraction of O2 from inspired air (EgO2) and blood EbO2), and capacitance coefficient of blood for oxygen (betabo2) were calculated. At 140 m, by comparison with predicted values for mammals of same body weight, pigeons at 22 degrees C extracted more O2 from the inspired gas, with lower fR, larger VT, similar Vg; they extracted O2 from the blood like mammals, with lower fH, larger VS, greater Vb, similar betabO2=70 mumol-L-1-torr-1. Acute exposure to 2 degrees C provoked a two-fold increase in MO2 which was achieved by doubling Vg and increasing O2 extraction from the blood. At 4000 m, in both series, pigeons hyperventilated within the first 30 min, with a resultant hypocapnic alkalosis comparable to that in mammals. Further hyperventilation with consequent greater hypocapnia and increase of arterial PO2 was complete beyond 3 hr. After a few weeks, the pH remained 0.07 above control normoxic value, Ht increased from 45 to 52%, betabO2 reached about 172 mumol-L-1-torr-1. At 2 degrees C, Vb also increased, mainly due to tachycardia.", "contents": "Ventilatory and circulatory O2 convection at 4000 m in pigeon at neutral or cold temperature. Awake domestic pigeons, either maintained at 22 degrees C (series I) or acutely exposed at 2 degrees C (series II), were studied in a hypobaric chamber at 140 m and at various stages during a 4-week exposure to 4000 m. Steady-state pulmonary ventilation (Vg) and breathing pattern (VT, fr), oxygen consumption (MO2), O2 concentrations and pressures in the arterial (a) and mixed venous blood (v), hematocrit (Ht) and acid-base status in arterial blood, systolic blood pressure and heart frequency (fH) were measured. From these data cardiac output (Vb) and stroke volume (Vs), ventilatory and circulatory requirements (Vg/MO2, Vb/MO2), extraction of O2 from inspired air (EgO2) and blood EbO2), and capacitance coefficient of blood for oxygen (betabo2) were calculated. At 140 m, by comparison with predicted values for mammals of same body weight, pigeons at 22 degrees C extracted more O2 from the inspired gas, with lower fR, larger VT, similar Vg; they extracted O2 from the blood like mammals, with lower fH, larger VS, greater Vb, similar betabO2=70 mumol-L-1-torr-1. Acute exposure to 2 degrees C provoked a two-fold increase in MO2 which was achieved by doubling Vg and increasing O2 extraction from the blood. At 4000 m, in both series, pigeons hyperventilated within the first 30 min, with a resultant hypocapnic alkalosis comparable to that in mammals. Further hyperventilation with consequent greater hypocapnia and increase of arterial PO2 was complete beyond 3 hr. After a few weeks, the pH remained 0.07 above control normoxic value, Ht increased from 45 to 52%, betabO2 reached about 172 mumol-L-1-torr-1. At 2 degrees C, Vb also increased, mainly due to tachycardia."}
{"id": "PMID:14366", "title": "The CSF HCO3 increase in hypercapnia relationshp to HCO3, glutamate, glutamine and NH3 in brain.", "content": "To study the role of carbonic anhydrase in the CSF [HCO3] increase in respiratory acidosis and its effect on brain ammonia, anesthetized rats were subjected to hypercapnia (7% CO2) for 2 hours. The animals received periodic intraventricular injections of either 'mock' CSF or 'mock' CSF and acetazolamide for 45 minutes prior and during hypercapnia when: (a) plasma [HCO3-] was allowed to increase normally and (2) plasma [HCO3] increase was prevented by i.v. HC1 infusion, CSF [HCO3] increased 8.5 mM/L after 2 hours of hypercapnia (delta PCO2 40) in the rats with intraventricular 'mock' CSF injections, and only 6 mM/L in the animals with acetazolamide injections. CSF [HCO3-] increased 7 mM/L during hypercapnia and HCl infusion with intraventricular 'mock' CSF injections, but only 2 mM/L with acetazolamide injections. Changes in total brain CO2 (increase) and brain glutamic acid (decrease) in hypercapnia were not affected by intraventricular acetazolamide and i.v. HCl. The increase of brain NH4+ and glutamine in hypercapnia was reduced in these conditions. It is concluded that there are at least two sources for the CSF [HCO3-] increase in hypercapnia; one formed in the CNS and dependent on carbonic anhydrase, and the other derived from plasma [HCO3-] increase.", "contents": "The CSF HCO3 increase in hypercapnia relationshp to HCO3, glutamate, glutamine and NH3 in brain. To study the role of carbonic anhydrase in the CSF [HCO3] increase in respiratory acidosis and its effect on brain ammonia, anesthetized rats were subjected to hypercapnia (7% CO2) for 2 hours. The animals received periodic intraventricular injections of either 'mock' CSF or 'mock' CSF and acetazolamide for 45 minutes prior and during hypercapnia when: (a) plasma [HCO3-] was allowed to increase normally and (2) plasma [HCO3] increase was prevented by i.v. HC1 infusion, CSF [HCO3] increased 8.5 mM/L after 2 hours of hypercapnia (delta PCO2 40) in the rats with intraventricular 'mock' CSF injections, and only 6 mM/L in the animals with acetazolamide injections. CSF [HCO3-] increased 7 mM/L during hypercapnia and HCl infusion with intraventricular 'mock' CSF injections, but only 2 mM/L with acetazolamide injections. Changes in total brain CO2 (increase) and brain glutamic acid (decrease) in hypercapnia were not affected by intraventricular acetazolamide and i.v. HCl. The increase of brain NH4+ and glutamine in hypercapnia was reduced in these conditions. It is concluded that there are at least two sources for the CSF [HCO3-] increase in hypercapnia; one formed in the CNS and dependent on carbonic anhydrase, and the other derived from plasma [HCO3-] increase."}
{"id": "PMID:14392", "title": "Preparation of 125I-labeled synthetic porcine secretin for radioimmunoassay.", "content": "Synthetic porcine secretion was labelled by the conjugation-labelling method of Bolton & Hunter, the lactoperoxidase method, the gaseous diffusion method, and the chloramine-T method. The chloramine-T technique was adapted as routine method. Ten mug (3.27 nmol) peptide was reacted with 5 mCi of Na125I at a concentration of chloramine-T of 1.3 mmol/l. Synthetic secretin was suitable for labelling for at least eight months when stored as dry matter in nitrogen-filled glass ampoules. Purification and separation of labelled from unlabelled hormone was carried out by gel-permeation chromatography on Sephadex G-50 superfine. The labelled preparation had a specific radioactivity of 405 +/- 33 muCi/nmol (mean +/- SEM., n = 9) and was unable for six days. 6-tyrosyl-secretin took more iodine compared to porcine synthetic secretin but had lower immunoreactivity with all antisera tested.", "contents": "Preparation of 125I-labeled synthetic porcine secretin for radioimmunoassay. Synthetic porcine secretion was labelled by the conjugation-labelling method of Bolton & Hunter, the lactoperoxidase method, the gaseous diffusion method, and the chloramine-T method. The chloramine-T technique was adapted as routine method. Ten mug (3.27 nmol) peptide was reacted with 5 mCi of Na125I at a concentration of chloramine-T of 1.3 mmol/l. Synthetic secretin was suitable for labelling for at least eight months when stored as dry matter in nitrogen-filled glass ampoules. Purification and separation of labelled from unlabelled hormone was carried out by gel-permeation chromatography on Sephadex G-50 superfine. The labelled preparation had a specific radioactivity of 405 +/- 33 muCi/nmol (mean +/- SEM., n = 9) and was unable for six days. 6-tyrosyl-secretin took more iodine compared to porcine synthetic secretin but had lower immunoreactivity with all antisera tested."}
{"id": "PMID:14393", "title": "Microbial and salivary conditions in 9- to 12-year-old children.", "content": "The prevalence of S. mutans and lactobacilli, the salivary secretion rate, and salivary pH and buffer capacity were examined in 655 children 9-12 years old. Some of these factors were correlated with the frequency of caries. Positive correlations were observed between for example S. mutans and lactobacilli, between S. mutans and incipient smooth surface caries, and between lactobacilli and open carious lesion. A high proportion of the children showed large numbers of S. mutans and lactobacilli.", "contents": "Microbial and salivary conditions in 9- to 12-year-old children. The prevalence of S. mutans and lactobacilli, the salivary secretion rate, and salivary pH and buffer capacity were examined in 655 children 9-12 years old. Some of these factors were correlated with the frequency of caries. Positive correlations were observed between for example S. mutans and lactobacilli, between S. mutans and incipient smooth surface caries, and between lactobacilli and open carious lesion. A high proportion of the children showed large numbers of S. mutans and lactobacilli."}
{"id": "PMID:14394", "title": "Oral complications in anorexia nervosa.", "content": "Anorexia nervosa (AN), a psychosomatic disease mainly affecting young women, is characterized by conscious starvation, periods of excessive carbohydrate intake and often deliberate vomiting. Medical history, dental examination, and saliva tests of 39 patients aged 14 to 42 years, having suffered from AN for periods of 1 to 20 years, showed dental caries, due to excessive carbohydrate consumption, in all subjects, often in a rampant form. In patients with a history of intense vomiting (27 cases) severe lingual-occlusal erosion (perimylolysis) was nearly always present. Buccal erosion, mainly due to high consumption of acid fruits and drinks to relieve thirst caused by dehydration, was more frequent in vomiting than in non-vomiting patients. Subnormal values of saliva properties, owing to dehydration or xerostomia-inducing medication, were present in the majority of cases; the lowest values occurred in those vomiting. The association AN - vomiting - perimylolysis is discussed, as well as prophylactic and therapeutic measures. A medical, psychiatric, and dental survey of AN is presented.", "contents": "Oral complications in anorexia nervosa. Anorexia nervosa (AN), a psychosomatic disease mainly affecting young women, is characterized by conscious starvation, periods of excessive carbohydrate intake and often deliberate vomiting. Medical history, dental examination, and saliva tests of 39 patients aged 14 to 42 years, having suffered from AN for periods of 1 to 20 years, showed dental caries, due to excessive carbohydrate consumption, in all subjects, often in a rampant form. In patients with a history of intense vomiting (27 cases) severe lingual-occlusal erosion (perimylolysis) was nearly always present. Buccal erosion, mainly due to high consumption of acid fruits and drinks to relieve thirst caused by dehydration, was more frequent in vomiting than in non-vomiting patients. Subnormal values of saliva properties, owing to dehydration or xerostomia-inducing medication, were present in the majority of cases; the lowest values occurred in those vomiting. The association AN - vomiting - perimylolysis is discussed, as well as prophylactic and therapeutic measures. A medical, psychiatric, and dental survey of AN is presented."}
{"id": "PMID:14398", "title": "Phenylethanolamine: a new putative neurotransmitter in Aplysia.", "content": "Phenylethanolamine is present in the Aplysia nervous system in concentrations similar to that of octopamine. These are receptors that are very specific for phenylethanolamine, which on different neurons mediate sodium, chlorine, or potassium conductance increase responses. These observations indicate that phenylethanolamine may act as a neurotransmitter in Aplysia.", "contents": "Phenylethanolamine: a new putative neurotransmitter in Aplysia. Phenylethanolamine is present in the Aplysia nervous system in concentrations similar to that of octopamine. These are receptors that are very specific for phenylethanolamine, which on different neurons mediate sodium, chlorine, or potassium conductance increase responses. These observations indicate that phenylethanolamine may act as a neurotransmitter in Aplysia."}
{"id": "PMID:14395", "title": "Denture stomatitis-yeast occurrence and the pH of saliva and denture plaque.", "content": "The study comprised 30 denture wearers with generalized simple or granular inflammation in the palate and 30 without (controls). )easts, mostly Candida species, were cultivated from the maxillary dentures of all subjects with inflammation and of 23 controls. Hyphae were found in the maxillary denture smears from 28 subjects with inflammation and from 18 controls. Thus it seems unjustified to consider the occurrence of hyphae pathognomonic of denture stomatitis. The pH of whole saliva did not differ in the two groups (inflammation:mean pH 6.5, control:6.6). There was no clear relation between the pH of resting saliva and the amount of fungal cultures. Thirty minutes after a mouthrinse with 10 ml of a 25% sucrose solution, the mean saliva pH had dropped equally in both groups. With regard to the denture plaque, samples taken 40 min after the rinse indicated a more pronounced acid production in the plaque associated with inflammation. The pH of \"resting\" plaque was also lower in the inflammation than in the control group (mean maxillary pH 5.7 and 6.3 respectively, a=0.002). No association was found between the pH and the occurrence of hyphae in \"resting\" denture plaque. This supports the view that the pH is of no major importance for filamentation in vivo.", "contents": "Denture stomatitis-yeast occurrence and the pH of saliva and denture plaque. The study comprised 30 denture wearers with generalized simple or granular inflammation in the palate and 30 without (controls). )easts, mostly Candida species, were cultivated from the maxillary dentures of all subjects with inflammation and of 23 controls. Hyphae were found in the maxillary denture smears from 28 subjects with inflammation and from 18 controls. Thus it seems unjustified to consider the occurrence of hyphae pathognomonic of denture stomatitis. The pH of whole saliva did not differ in the two groups (inflammation:mean pH 6.5, control:6.6). There was no clear relation between the pH of resting saliva and the amount of fungal cultures. Thirty minutes after a mouthrinse with 10 ml of a 25% sucrose solution, the mean saliva pH had dropped equally in both groups. With regard to the denture plaque, samples taken 40 min after the rinse indicated a more pronounced acid production in the plaque associated with inflammation. The pH of \"resting\" plaque was also lower in the inflammation than in the control group (mean maxillary pH 5.7 and 6.3 respectively, a=0.002). No association was found between the pH and the occurrence of hyphae in \"resting\" denture plaque. This supports the view that the pH is of no major importance for filamentation in vivo."}
{"id": "PMID:14399", "title": "Possible cyclic nucleotide regulation of calcium mediating myocardial contraction.", "content": "An inhibitor of adenylate and guanylate cyclases was tested on strips of left atria from rabbits. Effects of catecholamines (cardiotonic) and of acetylcholine (cardiodepressive) were blocked, and positive force-frequency was converted to negative. Ouabain produced only contracture without positive inotropy. The cardiotonic effect of increased calcium remained. Data suggest that cyclic nucleotides modulate calcium associated with these stimuli.", "contents": "Possible cyclic nucleotide regulation of calcium mediating myocardial contraction. An inhibitor of adenylate and guanylate cyclases was tested on strips of left atria from rabbits. Effects of catecholamines (cardiotonic) and of acetylcholine (cardiodepressive) were blocked, and positive force-frequency was converted to negative. Ouabain produced only contracture without positive inotropy. The cardiotonic effect of increased calcium remained. Data suggest that cyclic nucleotides modulate calcium associated with these stimuli."}
{"id": "PMID:14400", "title": "Glutamine synthetase: glial localization in brain.", "content": "Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.", "contents": "Glutamine synthetase: glial localization in brain. Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain."}
{"id": "PMID:14401", "title": "Massive skeletal trauma in renal transplant patients.", "content": "A review of 251 renal transplants done at the Vanderbilt University Medical Center since October 1962 revealed three patients who had suffered subsequent skeletal injuries sufficient to cause hospitalization. In a 37-year-old woman, a closed fracture of the pelvis healed satisfactorily in the usual period of time. In a 30-year-old man, closed fractures healed well, but there was prolonged delay in the healing of massive open wounds resulting from crushing injuries of the lower extremities. He required prolonged hospitalization, but satisfactory result was achieved after early amputation and close cooperation between orthopedic and renal teams. No significant alterations in the function of either patient's transplanted kidney occurred. It is postulated that severe trauma in transplantation patients may become more common in the future, and certain guidelines for its management are set forth. With close cooperation between the orthopedic surgical and medical renal teams, a successful outcome can be expected.", "contents": "Massive skeletal trauma in renal transplant patients. A review of 251 renal transplants done at the Vanderbilt University Medical Center since October 1962 revealed three patients who had suffered subsequent skeletal injuries sufficient to cause hospitalization. In a 37-year-old woman, a closed fracture of the pelvis healed satisfactorily in the usual period of time. In a 30-year-old man, closed fractures healed well, but there was prolonged delay in the healing of massive open wounds resulting from crushing injuries of the lower extremities. He required prolonged hospitalization, but satisfactory result was achieved after early amputation and close cooperation between orthopedic and renal teams. No significant alterations in the function of either patient's transplanted kidney occurred. It is postulated that severe trauma in transplantation patients may become more common in the future, and certain guidelines for its management are set forth. With close cooperation between the orthopedic surgical and medical renal teams, a successful outcome can be expected."}
{"id": "PMID:14402", "title": "Pathophysiology of propranolol in hypertension.", "content": "Only recently approved for use in the treatment of hypertension in the US, the beta-adrenergic receptor blocking compound propranolol has been used elsewhere for this purpose since 1964. The exact mechanisms to explain why and how \"beta-blocking drugs\" reduce arterial pressure are not known with certainty, but possible explanations include: (1) \"resetting\" of the baroreceptors, (2) reduction of cardiac output, (3) adaptation of circulation (\"autoregulation\"), (4) inhibition of renin release, (5) central nervous system effects, (6) possible antihypertensive metabolites, and (7) other unknown mechanisms or a combination of known mechanisms. Propranolol alone has been demonstrated to be extremely effective in reducing arterial pressure. In addition, the combination of propranolol and vasodilator and diuretic drugs would be expected to reduce vascular resistance without reflexive cardiac stimulation and with prevention of sodium and fluid retention.", "contents": "Pathophysiology of propranolol in hypertension. Only recently approved for use in the treatment of hypertension in the US, the beta-adrenergic receptor blocking compound propranolol has been used elsewhere for this purpose since 1964. The exact mechanisms to explain why and how \"beta-blocking drugs\" reduce arterial pressure are not known with certainty, but possible explanations include: (1) \"resetting\" of the baroreceptors, (2) reduction of cardiac output, (3) adaptation of circulation (\"autoregulation\"), (4) inhibition of renin release, (5) central nervous system effects, (6) possible antihypertensive metabolites, and (7) other unknown mechanisms or a combination of known mechanisms. Propranolol alone has been demonstrated to be extremely effective in reducing arterial pressure. In addition, the combination of propranolol and vasodilator and diuretic drugs would be expected to reduce vascular resistance without reflexive cardiac stimulation and with prevention of sodium and fluid retention."}
{"id": "PMID:14415", "title": "Clottability and cross-linking reactivity of fibrin(ogen) following differential release of fibrinopeptides A and B.", "content": "Human fibrinogen was treated at pH 6.0, 7.3 and 9.0 with thrombin, batroxobin (thrombin-like fraction of Bothrops atrox venom) or an extract of the venom from Ancistrodon contortrix contortrix. These three enzymes released the NH2-terminal fibrinopeptides A and B at different rates. Thrombin-free, preactivated factor XIII (factor XIIIa) was added to incubation mixtures to stabilize resulting fibrin(ogen) aggregates. Cross-linking of gamma-chains and the size of covalently linked fibrin-fibrinogen oligomers were studied in an early stage of fibrinopeptide cleavage using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Batroxobin (pH 7.3) and thrombin (pH 6.0) preferentially released fibrinopeptide A, and resulting fibrin aggregates became rapidly insoluble. However, when fibrinopeptide B was removed with the contortrix enzyme, soluble cross-linked oligomers appeared initially. The opaque fibrin clots, produced by thrombin (pH 6.0) or contortrix procoagulant fraction (pH 7.3), were found to be devoid of alpha-polymers even after prolonged incubation with factor XIIIa. Our data suggest that the solubility and opacity of fibrin networks are not primarily related to the type of the cross-link (gamma-gamma versus alpha-alpha interactions).", "contents": "Clottability and cross-linking reactivity of fibrin(ogen) following differential release of fibrinopeptides A and B. Human fibrinogen was treated at pH 6.0, 7.3 and 9.0 with thrombin, batroxobin (thrombin-like fraction of Bothrops atrox venom) or an extract of the venom from Ancistrodon contortrix contortrix. These three enzymes released the NH2-terminal fibrinopeptides A and B at different rates. Thrombin-free, preactivated factor XIII (factor XIIIa) was added to incubation mixtures to stabilize resulting fibrin(ogen) aggregates. Cross-linking of gamma-chains and the size of covalently linked fibrin-fibrinogen oligomers were studied in an early stage of fibrinopeptide cleavage using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Batroxobin (pH 7.3) and thrombin (pH 6.0) preferentially released fibrinopeptide A, and resulting fibrin aggregates became rapidly insoluble. However, when fibrinopeptide B was removed with the contortrix enzyme, soluble cross-linked oligomers appeared initially. The opaque fibrin clots, produced by thrombin (pH 6.0) or contortrix procoagulant fraction (pH 7.3), were found to be devoid of alpha-polymers even after prolonged incubation with factor XIIIa. Our data suggest that the solubility and opacity of fibrin networks are not primarily related to the type of the cross-link (gamma-gamma versus alpha-alpha interactions)."}
{"id": "PMID:14416", "title": "Soluble fibrin complexes: separation as a function of pH and characterization.", "content": "1. The influence of the pH on the separation of high molecular weight derivatives obtained by a limited action of thrombin on fibrinogen was studied by agarose gel chromatography. When the pH of the elution buffer was 8.5, non crosslinked associations were easily separated in two peaks eluted prior to the fibrinogen peak: one contained a dimer, the other several high polymers. At pH 6.5, only the fibrinogen peak appeared: the fibrinogen molecule proteolysed by thrombin formed no stable associations at this pH and was eluted with the intact fibrinogen molecule. In the presence of factor XIII and Ca++, numerous associations were obtained which are independant of the pH. 2. The polypeptide chain composition of the different species separated at pH 8.5 was studied by SDS-polyacrylamide gel electrophoresis. This technic showed Aalpha, Bbeta and gamma chains in the fibrinogen peak, whereas in the chromatographic fractions containing the dimer four bands corresponding to Aalpha, alpha, Bbeta and gamma chains were found. In the peak containing the high polymers, only the presence of alpha, Bbeta and gamma chains was demonstrated. 3. These experimental results concerning the effect of pH on the formation of soluble complexes showed that the presence of fibrin monomers in fibrinogen solution was not sufficient to promote any associations. The formation of such derivatives is strongly dependent on the pH of the solution. This obviously can be explained by an influence of the pH either on the ionization of polymerisation sites and the intermolecular bonds between the complex units or on the unmasking of the polymerisation sites by a hypothetical pH induced conformational change of the fibrinogen molecule.", "contents": "Soluble fibrin complexes: separation as a function of pH and characterization. 1. The influence of the pH on the separation of high molecular weight derivatives obtained by a limited action of thrombin on fibrinogen was studied by agarose gel chromatography. When the pH of the elution buffer was 8.5, non crosslinked associations were easily separated in two peaks eluted prior to the fibrinogen peak: one contained a dimer, the other several high polymers. At pH 6.5, only the fibrinogen peak appeared: the fibrinogen molecule proteolysed by thrombin formed no stable associations at this pH and was eluted with the intact fibrinogen molecule. In the presence of factor XIII and Ca++, numerous associations were obtained which are independant of the pH. 2. The polypeptide chain composition of the different species separated at pH 8.5 was studied by SDS-polyacrylamide gel electrophoresis. This technic showed Aalpha, Bbeta and gamma chains in the fibrinogen peak, whereas in the chromatographic fractions containing the dimer four bands corresponding to Aalpha, alpha, Bbeta and gamma chains were found. In the peak containing the high polymers, only the presence of alpha, Bbeta and gamma chains was demonstrated. 3. These experimental results concerning the effect of pH on the formation of soluble complexes showed that the presence of fibrin monomers in fibrinogen solution was not sufficient to promote any associations. The formation of such derivatives is strongly dependent on the pH of the solution. This obviously can be explained by an influence of the pH either on the ionization of polymerisation sites and the intermolecular bonds between the complex units or on the unmasking of the polymerisation sites by a hypothetical pH induced conformational change of the fibrinogen molecule."}
{"id": "PMID:14417", "title": "The host component of the popliteal lymph node graft-versus-host (GVH) reaction. Identification of cells in the node and kinetics of cell proliferation.", "content": "The cellular composition of rat popliteal lymph nodes undergoing a GVH reaction was examined. The great majority of cells isolated from the nodes were lymphocytes, while the contribution of phagocytic cells was negligible (less than 5%). Both T and B cells were present in GVH nodes. However, the proportion of B cells was higher than in normal lymph nodes (40-50% vs 30%). Cells synthesizing DNA were enumerated autoradiographically in sections of GVH nodes up to day 7 of the response. A significant increase in the proportion of 3H thymidine labelled cells had already been found on the third day of the GVH response, before lymph node enlargement was apparent. Of the differnt days tested a maximum of 6% labelled cells was found on day 7. Liquid scintillation counting of cell suspension from such nodes showed an even higher increase in 3H thymidine incorporation in GVH vs normal nodes. These findings indicate that cell proliferation is a central mechanism behind the lymph node enlargement.", "contents": "The host component of the popliteal lymph node graft-versus-host (GVH) reaction. Identification of cells in the node and kinetics of cell proliferation. The cellular composition of rat popliteal lymph nodes undergoing a GVH reaction was examined. The great majority of cells isolated from the nodes were lymphocytes, while the contribution of phagocytic cells was negligible (less than 5%). Both T and B cells were present in GVH nodes. However, the proportion of B cells was higher than in normal lymph nodes (40-50% vs 30%). Cells synthesizing DNA were enumerated autoradiographically in sections of GVH nodes up to day 7 of the response. A significant increase in the proportion of 3H thymidine labelled cells had already been found on the third day of the GVH response, before lymph node enlargement was apparent. Of the differnt days tested a maximum of 6% labelled cells was found on day 7. Liquid scintillation counting of cell suspension from such nodes showed an even higher increase in 3H thymidine incorporation in GVH vs normal nodes. These findings indicate that cell proliferation is a central mechanism behind the lymph node enlargement."}
{"id": "PMID:14419", "title": "Effects of general anesthetics on search in memory in man.", "content": "Recovery of search functions in long-term memory following several hours of anesthesia was studied on human volunteers. Verbal as well as visual search was assessed. The anesthetics used, fluroxene and halothane, slowed down considerably the verbal search for the first few hours following anesthesia, but had very little effect on the following day. No effect was observed a week later. Visual search was not affected at all, in accordance with previous findings indicating a selective effect of low concentrations of inhalation anesthetics on verbal memory.", "contents": "Effects of general anesthetics on search in memory in man. Recovery of search functions in long-term memory following several hours of anesthesia was studied on human volunteers. Verbal as well as visual search was assessed. The anesthetics used, fluroxene and halothane, slowed down considerably the verbal search for the first few hours following anesthesia, but had very little effect on the following day. No effect was observed a week later. Visual search was not affected at all, in accordance with previous findings indicating a selective effect of low concentrations of inhalation anesthetics on verbal memory."}
{"id": "PMID:14422", "title": "Absorption, metabolism and excretion of safrole in the rat and man.", "content": "The metabolic disposition of different doses of [14C] safrole were studied in rat and man. In both species, small amounts of orally administered safrole were absorbed rapidly and then excreted almost entirely within 24 h in the urine. In the rat, when the dose was raised from 0.6 to 750 mg/kg, a marked decrease in the rate of elimination occurred as only 25% of the dose was excreted in the urine in 24 h. Furthermore, at the high dose level, plasma and tissue concentrations of both unchanged safrole and its metabolites remained elevated for 48 h probably indicating impairment of the degradation/excretion pathways. The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man.", "contents": "Absorption, metabolism and excretion of safrole in the rat and man. The metabolic disposition of different doses of [14C] safrole were studied in rat and man. In both species, small amounts of orally administered safrole were absorbed rapidly and then excreted almost entirely within 24 h in the urine. In the rat, when the dose was raised from 0.6 to 750 mg/kg, a marked decrease in the rate of elimination occurred as only 25% of the dose was excreted in the urine in 24 h. Furthermore, at the high dose level, plasma and tissue concentrations of both unchanged safrole and its metabolites remained elevated for 48 h probably indicating impairment of the degradation/excretion pathways. The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man."}
{"id": "PMID:14427", "title": "[Radiation response of mitochondria in dependence on their metabolic status (author's transl)].", "content": "The influence of the metabolic status of mitochondria upon their radiation response was studied. It turned out that the reduction of pyridine nucleotides by addition of beta-hydroxybutyrate (BOH) and the decrease through respiration were distinctly impaired in mitochondria with a substrate deficit by an irradiation with 2.7 krd already. The evolution of the lesion depends on the incubation conditions following irradiation, a presence of BOH having protective effects. The general redox level seems to be essential for radiation response of mitochondria. An exit of NAD from mitochondria has proved to be the main cause for inhibition of the respiratory BOH-consumption.", "contents": "[Radiation response of mitochondria in dependence on their metabolic status (author's transl)]. The influence of the metabolic status of mitochondria upon their radiation response was studied. It turned out that the reduction of pyridine nucleotides by addition of beta-hydroxybutyrate (BOH) and the decrease through respiration were distinctly impaired in mitochondria with a substrate deficit by an irradiation with 2.7 krd already. The evolution of the lesion depends on the incubation conditions following irradiation, a presence of BOH having protective effects. The general redox level seems to be essential for radiation response of mitochondria. An exit of NAD from mitochondria has proved to be the main cause for inhibition of the respiratory BOH-consumption."}
{"id": "PMID:14428", "title": "Chemiluminescence microanalysis of substrates and enzymes.", "content": "Extracts from bioluminescent organisms are increasingly used for analysis of small amounts of substrates and enzymes. The light emission is in some organisms related to the conversion of substrates and cofactors of central metabolic importance. Extracts from such organisms are particularly valuable for analytical applications. This is quite obvious in the firefly where the energy, required for light production, is derived from ATP and in a couple of strains of luminescent bacteria where reduced pyridine nucleotides through reduction of flavine mononucleotide is utilized in the light reaction. It deserved to be noted that many biochemical reactions can be coupled more or less directly to the conversion of ATP, NAD(H), NADP(H) and FMN(H), thus providing the basis for a great variety of analyses. Special kinds of bioluminescent reactions are also of considerable interest, as for instance the relationship between \"active sulphate\" and PAP, which participate in the formation of light in the sea pansy (Renilla reniformis). High sensitivities are often reached in chemiluminescence analysis making the technique suitable for samples composed of a small number of cells. How bioluminescence has been employed in these kinds of microanalyses is examplified in studies of nucleotides, metabolites and enzymes with low activities.", "contents": "Chemiluminescence microanalysis of substrates and enzymes. Extracts from bioluminescent organisms are increasingly used for analysis of small amounts of substrates and enzymes. The light emission is in some organisms related to the conversion of substrates and cofactors of central metabolic importance. Extracts from such organisms are particularly valuable for analytical applications. This is quite obvious in the firefly where the energy, required for light production, is derived from ATP and in a couple of strains of luminescent bacteria where reduced pyridine nucleotides through reduction of flavine mononucleotide is utilized in the light reaction. It deserved to be noted that many biochemical reactions can be coupled more or less directly to the conversion of ATP, NAD(H), NADP(H) and FMN(H), thus providing the basis for a great variety of analyses. Special kinds of bioluminescent reactions are also of considerable interest, as for instance the relationship between \"active sulphate\" and PAP, which participate in the formation of light in the sea pansy (Renilla reniformis). High sensitivities are often reached in chemiluminescence analysis making the technique suitable for samples composed of a small number of cells. How bioluminescence has been employed in these kinds of microanalyses is examplified in studies of nucleotides, metabolites and enzymes with low activities."}
{"id": "PMID:14431", "title": "A contribution to the formation mechanism of calcium oxalate urinary calculi. II. In vitro experiments concerning the theory of the formation of Whewellite and Weddellite urinary calculi.", "content": "In vitro investigations of the formation of Whewellite or Weddellite are described. By means of different precipitation models the influence of cationic minerals on the formation of Weddellite could be observed. The possible conversion of Weddellite into Whewellite in vivo is demonstrated by in vitro experiments. A theory of the formation of Weddellite or Whewellite urinary calculi is developed on the basis of the results obtained.", "contents": "A contribution to the formation mechanism of calcium oxalate urinary calculi. II. In vitro experiments concerning the theory of the formation of Whewellite and Weddellite urinary calculi. In vitro investigations of the formation of Whewellite or Weddellite are described. By means of different precipitation models the influence of cationic minerals on the formation of Weddellite could be observed. The possible conversion of Weddellite into Whewellite in vivo is demonstrated by in vitro experiments. A theory of the formation of Weddellite or Whewellite urinary calculi is developed on the basis of the results obtained."}
{"id": "PMID:14432", "title": "A contribution to the formation mechanism of calcium oxalate urinary calculi. III. On the role of magnesium in the formation of oxalate calculi.", "content": "The influence of magnesium in vitro on the precipitation of calcium oxalate was investigated. Even at maximum physiological magnesium concentrations a litholytic effect could not be observed, but the retardation of the calcium oxalate crystallization caused by magnesium might be decisive for a reduction in calculi formation. The enlargement of the calcium oxalate crystals and aggregates caused by the retardation of crystallization, however, should be regarded as a contraindicating factor for Mg therapy in oxalate calculous disease. It is safe to say that high magnesium concentrations prevent the conversion into Whewellite of the calcium oxalate calculi substance primarily formed as Weddellite.", "contents": "A contribution to the formation mechanism of calcium oxalate urinary calculi. III. On the role of magnesium in the formation of oxalate calculi. The influence of magnesium in vitro on the precipitation of calcium oxalate was investigated. Even at maximum physiological magnesium concentrations a litholytic effect could not be observed, but the retardation of the calcium oxalate crystallization caused by magnesium might be decisive for a reduction in calculi formation. The enlargement of the calcium oxalate crystals and aggregates caused by the retardation of crystallization, however, should be regarded as a contraindicating factor for Mg therapy in oxalate calculous disease. It is safe to say that high magnesium concentrations prevent the conversion into Whewellite of the calcium oxalate calculi substance primarily formed as Weddellite."}
{"id": "PMID:14447", "title": "[Age-dependence of catecholamine effects in man. IV. Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics].", "content": "In order to characterize age differences in the lipolytic effect of catecholamines on tests of subcutaneous adipose tissue of test persons aged from 0.1 to 10 years, from 20 to 40 years, and from 60 to 75 years the influence of propranolol, phentolamine and theophyllin on the release of glycerol by isoprenalin and adrenalin was investigated. Propranolol (10(8) and 10(5) mol/1) inhibits the lipolysis in the adipose tissue of all age groups stimulated by isoprenalin (10(6)and 10(5) mol/1). The following Ki-values were calculated: 2x10(6) mol/1in the tissue of adults, 0.5 x 10(6) mol/1 in the infantile adipose tissue, 0.2 X 10(6) mol/1 in the tissue of old persons. Phentolamine (10(5) mol/1) increases the lipolytic effect of adrenalin (10(5) mol/1), there are no age differences. Theophyllin (10 (2) mol/1) increases the release of glycerol induced by isoprenalin (10(5) mol/1) in infantile and adult adipose tissue, however, it has no influence on them in the adipose tissue of old man. The findings suggest the higher sensitivity of the fat cells of the ageing organism to beta-adrenergics underlies a higher affinity of the adrenergics to the specific beta-adrenoceptors in the cytoplasm membrane of the adipocytes. The more intensive lipid mobilization in old age by beta-adrenergics is explained by a low activity of the cAMP-phosphodiesterase of the fat cells and by the higher and possibly longer lasting increase of intracellular cAMP in this age group.", "contents": "[Age-dependence of catecholamine effects in man. IV. Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics]. In order to characterize age differences in the lipolytic effect of catecholamines on tests of subcutaneous adipose tissue of test persons aged from 0.1 to 10 years, from 20 to 40 years, and from 60 to 75 years the influence of propranolol, phentolamine and theophyllin on the release of glycerol by isoprenalin and adrenalin was investigated. Propranolol (10(8) and 10(5) mol/1) inhibits the lipolysis in the adipose tissue of all age groups stimulated by isoprenalin (10(6)and 10(5) mol/1). The following Ki-values were calculated: 2x10(6) mol/1in the tissue of adults, 0.5 x 10(6) mol/1 in the infantile adipose tissue, 0.2 X 10(6) mol/1 in the tissue of old persons. Phentolamine (10(5) mol/1) increases the lipolytic effect of adrenalin (10(5) mol/1), there are no age differences. Theophyllin (10 (2) mol/1) increases the release of glycerol induced by isoprenalin (10(5) mol/1) in infantile and adult adipose tissue, however, it has no influence on them in the adipose tissue of old man. The findings suggest the higher sensitivity of the fat cells of the ageing organism to beta-adrenergics underlies a higher affinity of the adrenergics to the specific beta-adrenoceptors in the cytoplasm membrane of the adipocytes. The more intensive lipid mobilization in old age by beta-adrenergics is explained by a low activity of the cAMP-phosphodiesterase of the fat cells and by the higher and possibly longer lasting increase of intracellular cAMP in this age group."}
{"id": "PMID:14460", "title": "[Stability in drinking and surface water of nine virus species from different genera (author's transl)].", "content": "The stability of nine viruses, Aujeszky, Sindbis, Vesicular Stomatitis, Newcastle Disease, Vaccinia, FMD, HCC, Reo and Teschen virus in drinking and surface water was investigated comparatively at temperatures of 9 and 15 degrees C as well as the influence of water factors like seasonal difference in temperature, pH value, hardness and sort of water. The results can be summarized as follows: 1. At temperatures of 9 to 15 degrees C the majority of the viruses remained stabil in natural water for an astonishing long time. 2. Starting with virus concentration of about 10(4) infectious units per ml Teschen, Vaccinia, Reo, HCC and ND virus could mostly be demonstrated in water longer than 200 days and FMD, Aujeszky, Vesicular Stomatitis and Sindbis virus for 20 to 50 days on average at 9 degrees C. The stability of the viruses investigated decreased in water in the named turn. 3. Based on these results it can be assumed that under natural conditions with very low virus content of some particles the labile viruses such as Toga, Herpes, Rhabdo and pH labile Picorna remain infectious in water for some days. They should not have any importance as water contaminants. More resistant viruses like Paramyxo may keep infectious for weeks and very stabile viruses such as Entero, Reo, Adeno and Pox viruses several weeks to months. 4. As to factors temperature, pH, hardness and sort of water-within the naturally differing range-only the temperature and only in the case of less resistant viruses showed significant influence on the virus stability in water.", "contents": "[Stability in drinking and surface water of nine virus species from different genera (author's transl)]. The stability of nine viruses, Aujeszky, Sindbis, Vesicular Stomatitis, Newcastle Disease, Vaccinia, FMD, HCC, Reo and Teschen virus in drinking and surface water was investigated comparatively at temperatures of 9 and 15 degrees C as well as the influence of water factors like seasonal difference in temperature, pH value, hardness and sort of water. The results can be summarized as follows: 1. At temperatures of 9 to 15 degrees C the majority of the viruses remained stabil in natural water for an astonishing long time. 2. Starting with virus concentration of about 10(4) infectious units per ml Teschen, Vaccinia, Reo, HCC and ND virus could mostly be demonstrated in water longer than 200 days and FMD, Aujeszky, Vesicular Stomatitis and Sindbis virus for 20 to 50 days on average at 9 degrees C. The stability of the viruses investigated decreased in water in the named turn. 3. Based on these results it can be assumed that under natural conditions with very low virus content of some particles the labile viruses such as Toga, Herpes, Rhabdo and pH labile Picorna remain infectious in water for some days. They should not have any importance as water contaminants. More resistant viruses like Paramyxo may keep infectious for weeks and very stabile viruses such as Entero, Reo, Adeno and Pox viruses several weeks to months. 4. As to factors temperature, pH, hardness and sort of water-within the naturally differing range-only the temperature and only in the case of less resistant viruses showed significant influence on the virus stability in water."}
{"id": "PMID:14455", "title": "[Gamma-glutamyltranspeptidase in chronic polyarthritis. I. Comparison with a control group and relationship with alkaline phosphatase].", "content": "Gamma-GT, alcaline phosphatase and other parameters of abnormal liver functions were estimated in 54 consecutive in-patients having active RA but without a previous history or clinical signs of liver disease, and compared with a matched control group, suffering from degenerative rheumatic disease. There was a slight to moderate elevation of gamma-GT in 40.4% of the RA-patients (mean value 27.2 IU/l) and in 32.1% (mean value 22.3 IU/l) of the control group, respectively. The difference was not significant. Abnormal values in the control group occurred mainly in patients with peri-arthropathia of the shoulder, before mobilisation under anaethetic (3 of 5) and - coxarthrosis before total hip replacement (4 of 12). Alkaline phosphatase was elevated in 25.9% of the RA-patients (mean value 41.3 +/- 21.9 IU/l) and in 14.8% of the control group (mean value 34.3 +/- 15.9 IU/l). The difference was significant. There was a correlation between gamma-GT and alcaline phosphatase in the RA-group (r = 0.549, p less than 0.001) but not in the control group (r = 0.102). Abnormal values found in the control group were mainly found among patients with osteoporosis, following fractures, and coxarthrosis. The frequency of abnormal results and the value of the means increased with raising disease activity. Two groups of 30 and 32 patients, respectively, were examined at intervals of 2 or 4 weeks over a period of 6-10 and 18 months, respectively, and showed temporary elevations os gamma-GT in 3/4 of all patients, of GOT in 2/3 of alcaline phosphatase in 1/2 and of GPT in 1/3. Compared with other parameters of liver disease gamma-GT did not react in a different but in a more sensitive way. In our opinion it is the most sensitive indicator of reactive changes of the liver in RA.", "contents": "[Gamma-glutamyltranspeptidase in chronic polyarthritis. I. Comparison with a control group and relationship with alkaline phosphatase]. Gamma-GT, alcaline phosphatase and other parameters of abnormal liver functions were estimated in 54 consecutive in-patients having active RA but without a previous history or clinical signs of liver disease, and compared with a matched control group, suffering from degenerative rheumatic disease. There was a slight to moderate elevation of gamma-GT in 40.4% of the RA-patients (mean value 27.2 IU/l) and in 32.1% (mean value 22.3 IU/l) of the control group, respectively. The difference was not significant. Abnormal values in the control group occurred mainly in patients with peri-arthropathia of the shoulder, before mobilisation under anaethetic (3 of 5) and - coxarthrosis before total hip replacement (4 of 12). Alkaline phosphatase was elevated in 25.9% of the RA-patients (mean value 41.3 +/- 21.9 IU/l) and in 14.8% of the control group (mean value 34.3 +/- 15.9 IU/l). The difference was significant. There was a correlation between gamma-GT and alcaline phosphatase in the RA-group (r = 0.549, p less than 0.001) but not in the control group (r = 0.102). Abnormal values found in the control group were mainly found among patients with osteoporosis, following fractures, and coxarthrosis. The frequency of abnormal results and the value of the means increased with raising disease activity. Two groups of 30 and 32 patients, respectively, were examined at intervals of 2 or 4 weeks over a period of 6-10 and 18 months, respectively, and showed temporary elevations os gamma-GT in 3/4 of all patients, of GOT in 2/3 of alcaline phosphatase in 1/2 and of GPT in 1/3. Compared with other parameters of liver disease gamma-GT did not react in a different but in a more sensitive way. In our opinion it is the most sensitive indicator of reactive changes of the liver in RA."}
{"id": "PMID:14461", "title": "Relationships between chemical structure and antiviral activity of some biguanide derivatives.", "content": "The aim of this report was to indicate the correlation between chemical structure and antiviral activity of some biguanide derivatives obtained according to Monsanto Chemicals Ltd. Neth. Appl. 289. 283. The studies were carried out on the culture of monkey kidney cells infected with parainfluenza Sendai virus and on the mice infected with influenza virus. The increase of antiviral activities of N-Phenylbiguanide and N-p-Ethoxyphenylbiguanide was estimated.", "contents": "Relationships between chemical structure and antiviral activity of some biguanide derivatives. The aim of this report was to indicate the correlation between chemical structure and antiviral activity of some biguanide derivatives obtained according to Monsanto Chemicals Ltd. Neth. Appl. 289. 283. The studies were carried out on the culture of monkey kidney cells infected with parainfluenza Sendai virus and on the mice infected with influenza virus. The increase of antiviral activities of N-Phenylbiguanide and N-p-Ethoxyphenylbiguanide was estimated."}
{"id": "PMID:14456", "title": "[Gamma-glutamyltranspeptidase in chronic polyarthritis. II. Influence of drugs].", "content": "Thirty outpatients with active RA were treated with Sudoxicam, a nonsteroidal antirheumatic drug, for periods of 6-10 months. Gamma-GT, alkaline phosphatase and transaminase were estimated at 2 week intervals. During treatment, the frequently elevated values showed a significant tendency towards normality (time trend analysis). During a second drug trial with Piroxicam in 32 RA outpatients over a period of 18 months, the mean value of gamma-GT and alkaline phosphatase did not decrease significantly. With regards to liver function tests, there was no significant difference between 19 patients receiving and 13 patients not receiving simultaneous gold therapy. During gold treatment periods of 26 patients with a total dose of 3.8 g Fosfocrisolo (0.8 g Au) the mean value of gamma-GT decreased from 26 to IU/l. Cyclophosphamide treatment of 13 patients, with daily doses of 50-150 mg to a total dose auf 48 g, had no significant influence on gamma-GT and alkaline phosphatase. Our results indicate that the very frequent elevations of gamma-GT and of other liver data in RA are caused by the rheumatoid process itself and not induced by drugs.", "contents": "[Gamma-glutamyltranspeptidase in chronic polyarthritis. II. Influence of drugs]. Thirty outpatients with active RA were treated with Sudoxicam, a nonsteroidal antirheumatic drug, for periods of 6-10 months. Gamma-GT, alkaline phosphatase and transaminase were estimated at 2 week intervals. During treatment, the frequently elevated values showed a significant tendency towards normality (time trend analysis). During a second drug trial with Piroxicam in 32 RA outpatients over a period of 18 months, the mean value of gamma-GT and alkaline phosphatase did not decrease significantly. With regards to liver function tests, there was no significant difference between 19 patients receiving and 13 patients not receiving simultaneous gold therapy. During gold treatment periods of 26 patients with a total dose of 3.8 g Fosfocrisolo (0.8 g Au) the mean value of gamma-GT decreased from 26 to IU/l. Cyclophosphamide treatment of 13 patients, with daily doses of 50-150 mg to a total dose auf 48 g, had no significant influence on gamma-GT and alkaline phosphatase. Our results indicate that the very frequent elevations of gamma-GT and of other liver data in RA are caused by the rheumatoid process itself and not induced by drugs."}
{"id": "PMID:14462", "title": "[Changes in the acid-base condition and gas composition of the blood in meningoencephalitis of meningococcal etiology].", "content": "A study of the acid-base state in meningococcous meningoencephalitis demonstrates that there are different metabolic changes: metabolic acidosis, metabolic alkolosis, respiratory alkalosis and metabolic and respiratory alkalosis. These studies also detected a significant correlation between the character of these changes and syndromes of brain lesions. Deep lesions are characterized by metabolic acidosis, basal-stem lesions by respiratory alkalosis, multiple lesions--by metabolic alkalosis. These data give ground to speak of the significance of brain pathology in the pathogenesis of general metabolic disturbances in meningococcus infections.", "contents": "[Changes in the acid-base condition and gas composition of the blood in meningoencephalitis of meningococcal etiology]. A study of the acid-base state in meningococcous meningoencephalitis demonstrates that there are different metabolic changes: metabolic acidosis, metabolic alkolosis, respiratory alkalosis and metabolic and respiratory alkalosis. These studies also detected a significant correlation between the character of these changes and syndromes of brain lesions. Deep lesions are characterized by metabolic acidosis, basal-stem lesions by respiratory alkalosis, multiple lesions--by metabolic alkalosis. These data give ground to speak of the significance of brain pathology in the pathogenesis of general metabolic disturbances in meningococcus infections."}
{"id": "PMID:14464", "title": "[Purification and various properties of NADP+-dependent alcohol dehydrogenase from Acinetobacter calcoaceticus].", "content": "The constitutive NADP+-dependent alcohol dehydrogenase from Acinetobacter calcoaceticus can be accumulated about 50 fold in 3 purification steps. The end-product shows in the analytical polyacrylamide gel electrophoresis only one active enzyme band. The molecular weight of the enzyme was determined to be 235,000 by gel chromatography on Sephadex G 200, the smallest subunit shows a molecular weight of 61 000 on SDS electrophoresis. The isoelectric point is at 5.84. The KM values determined with primary aliphatic alcohols diminish in the range of the homologous order (C2--C10) with growing chain length. The KM value for hexanal is about 20 fold less than that for 1-hexanol.", "contents": "[Purification and various properties of NADP+-dependent alcohol dehydrogenase from Acinetobacter calcoaceticus]. The constitutive NADP+-dependent alcohol dehydrogenase from Acinetobacter calcoaceticus can be accumulated about 50 fold in 3 purification steps. The end-product shows in the analytical polyacrylamide gel electrophoresis only one active enzyme band. The molecular weight of the enzyme was determined to be 235,000 by gel chromatography on Sephadex G 200, the smallest subunit shows a molecular weight of 61 000 on SDS electrophoresis. The isoelectric point is at 5.84. The KM values determined with primary aliphatic alcohols diminish in the range of the homologous order (C2--C10) with growing chain length. The KM value for hexanal is about 20 fold less than that for 1-hexanol."}
{"id": "PMID:14465", "title": "Synthesis, turnover and compartment analysis of the free fatty acids in the placenta of rats.", "content": "The in vivo tracer method and in vitro acetate incorporation experiments were used to investigate the metabolism of placental free fatty acids. Analysis of data revealed that free fatty acids pass into the fetus from maternal plasma through a small placental compartment, which accounts for only 5 percent of all of the placental free fatty acids. The turnover time of this compartment is 0.57 min. The rate of placental fatty acid synthesis evaluated by both methods is very small and amounts to 0.003 mumols fatty acids/min/all placentas of one litter.", "contents": "Synthesis, turnover and compartment analysis of the free fatty acids in the placenta of rats. The in vivo tracer method and in vitro acetate incorporation experiments were used to investigate the metabolism of placental free fatty acids. Analysis of data revealed that free fatty acids pass into the fetus from maternal plasma through a small placental compartment, which accounts for only 5 percent of all of the placental free fatty acids. The turnover time of this compartment is 0.57 min. The rate of placental fatty acid synthesis evaluated by both methods is very small and amounts to 0.003 mumols fatty acids/min/all placentas of one litter."}
{"id": "PMID:14466", "title": "[Antihemolytic effect of various benzodiazepines on human erythrocytes].", "content": "The benzodiazepines, medazepam, chlorodiazepoxyde, and oxazepam, act antihemolytically just as chloropromazine in hypotonic NaCl solution on human erythrocytes. The effect depends on concentration and is biphasic with the exception of oxazepam. The maximal antihemolytic concentrations are for medazepam 9.1-10-5 M, for chlorodiazepoxyde 4.6-10-4 M and, respectively, 9.1-10-4 M for diazepam and oxazepam. No linear correlation exists between the concentration at maximal hemolytic protection and the lipid solubility.", "contents": "[Antihemolytic effect of various benzodiazepines on human erythrocytes]. The benzodiazepines, medazepam, chlorodiazepoxyde, and oxazepam, act antihemolytically just as chloropromazine in hypotonic NaCl solution on human erythrocytes. The effect depends on concentration and is biphasic with the exception of oxazepam. The maximal antihemolytic concentrations are for medazepam 9.1-10-5 M, for chlorodiazepoxyde 4.6-10-4 M and, respectively, 9.1-10-4 M for diazepam and oxazepam. No linear correlation exists between the concentration at maximal hemolytic protection and the lipid solubility."}
{"id": "PMID:14467", "title": "Studies on ligand binding of kidney bean leghemoglobin.", "content": "Absorption spectra of different ligand derivative;s of kidney bean leghemoglobin alpha have been recorded. The effect of pH on the absorption spectra of kidney bean leghemoglobin alpha has been studied. The pK of the acid-alkaline transition of the heme-linked water molecule is 8.25 and the pK for the acid dissociation of the heme group is 4.03. Affinities of kidney bean leghemoglobin for two different types of ligands have been studied in comparison with soybean leghemoglobins alpha and c and sperm whale myoglobin. All these leghemoglobins have similar affinities for the small anionic ligand fluoride ion, and they are only slightly more accessible to this ligand than is sperm whale myoglobin. Differences in the primary structure or in conformation of these proteins are reflected in the affinity for the bulky ligand imidazole. The accessibility to imidazole increases in the order sperm whale myoglobin less than soybean Lbalpha less than soybean Lbc less than kidney bean Lbalpha, and also low spin Lbalpha less than high spin Lbalpha. The results are discussed with respect to the amino acid sequences of the leghemoglobins.", "contents": "Studies on ligand binding of kidney bean leghemoglobin. Absorption spectra of different ligand derivative;s of kidney bean leghemoglobin alpha have been recorded. The effect of pH on the absorption spectra of kidney bean leghemoglobin alpha has been studied. The pK of the acid-alkaline transition of the heme-linked water molecule is 8.25 and the pK for the acid dissociation of the heme group is 4.03. Affinities of kidney bean leghemoglobin for two different types of ligands have been studied in comparison with soybean leghemoglobins alpha and c and sperm whale myoglobin. All these leghemoglobins have similar affinities for the small anionic ligand fluoride ion, and they are only slightly more accessible to this ligand than is sperm whale myoglobin. Differences in the primary structure or in conformation of these proteins are reflected in the affinity for the bulky ligand imidazole. The accessibility to imidazole increases in the order sperm whale myoglobin less than soybean Lbalpha less than soybean Lbc less than kidney bean Lbalpha, and also low spin Lbalpha less than high spin Lbalpha. The results are discussed with respect to the amino acid sequences of the leghemoglobins."}
{"id": "PMID:14468", "title": "Relative value of beta blockers and thiazides for initiating antihypertensive therapy. Beta blockers or thiazides in hypertension.", "content": "Fifty-five patients with mild to moderate, renal or essential hypertension were admitted to a double blind cross-over trial of 18 weeks, involving treatment periods with placebo, the thiazide bendrofluazide (15 mg daily) and the beta blocker atenolol (600 mg daily). Compared to the placebo period (190/117 mm Hg) the hypotensive effect of atenolol (-24/16 mm Hg) was more pronounced than the hypotensive effect of bendrofluazide (-17/6 mm Hg). Arguments in favor of initiating antihypertensive drug therapy with beta blocker were its more powerful hypotensive effect, the quicker onset of its action, less metabolic disturbance, decreased frequency of complaints and patient's preference. On thiazides body weight and the frequency of swollen ankles decreased. Plasma renin concentration was not found to have a strong predicting power for the hypotensive effect of atenolol or bendrofluazide but low renin patients showed a more pronounced blood pressure decrease on bendrofluazide and high renin patients, especially essential hypertensives, on atenolol. While these points can be a guide to therapy today, the preference of one drug over the other must eventually be based on their relative efficacy in decreasing morbidity and mortality from the hypertensive disease.", "contents": "Relative value of beta blockers and thiazides for initiating antihypertensive therapy. Beta blockers or thiazides in hypertension. Fifty-five patients with mild to moderate, renal or essential hypertension were admitted to a double blind cross-over trial of 18 weeks, involving treatment periods with placebo, the thiazide bendrofluazide (15 mg daily) and the beta blocker atenolol (600 mg daily). Compared to the placebo period (190/117 mm Hg) the hypotensive effect of atenolol (-24/16 mm Hg) was more pronounced than the hypotensive effect of bendrofluazide (-17/6 mm Hg). Arguments in favor of initiating antihypertensive drug therapy with beta blocker were its more powerful hypotensive effect, the quicker onset of its action, less metabolic disturbance, decreased frequency of complaints and patient's preference. On thiazides body weight and the frequency of swollen ankles decreased. Plasma renin concentration was not found to have a strong predicting power for the hypotensive effect of atenolol or bendrofluazide but low renin patients showed a more pronounced blood pressure decrease on bendrofluazide and high renin patients, especially essential hypertensives, on atenolol. While these points can be a guide to therapy today, the preference of one drug over the other must eventually be based on their relative efficacy in decreasing morbidity and mortality from the hypertensive disease."}
{"id": "PMID:14469", "title": "Stabilization and assay of a 17beta-hydroxysteroid dehydrogenase in the serum of pregnant women.", "content": "Up to the present the activity of the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in the blood of pregnant women has not been accurately measured because of its great instability. The enzyme was stabilized by mixing fresh serum with an equal volume of potassium phosphate buffer (100 mM, PH 7.4), containing 40% (v/v) glycerol, 40 muM oestradiol-17beta (Oe2) and 0.4% (v/v) ethanol. Under these conditions the 17beta-HSD was stable for several days at -20, +4 and +20 degrees C and resistant to heat denaturation at 60 degrees C. The Km-value for Oe2 with NAD or NADP as cosubstrate was 5 X 10(-6) or 2 X 10(-6) M, respectively. In the presence of NAD, Oe2 was oxidized twice as rapidly as with NADP. The Km-value for NAD was 10(-5) M. Under the conditions of assay [3H]oestrone formation was linear with time (3 h) and with protein concentration. Serum enzyme activities in normal pregnancies (between 20 and 60 muU/ml serum at the end of gestation) were nearly twice as high as those reported by other investigators. In normal single and twin births highest activities were obtained at the expulsion of the placenta which in all cases was followed by a rapid decrease in activity.", "contents": "Stabilization and assay of a 17beta-hydroxysteroid dehydrogenase in the serum of pregnant women. Up to the present the activity of the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in the blood of pregnant women has not been accurately measured because of its great instability. The enzyme was stabilized by mixing fresh serum with an equal volume of potassium phosphate buffer (100 mM, PH 7.4), containing 40% (v/v) glycerol, 40 muM oestradiol-17beta (Oe2) and 0.4% (v/v) ethanol. Under these conditions the 17beta-HSD was stable for several days at -20, +4 and +20 degrees C and resistant to heat denaturation at 60 degrees C. The Km-value for Oe2 with NAD or NADP as cosubstrate was 5 X 10(-6) or 2 X 10(-6) M, respectively. In the presence of NAD, Oe2 was oxidized twice as rapidly as with NADP. The Km-value for NAD was 10(-5) M. Under the conditions of assay [3H]oestrone formation was linear with time (3 h) and with protein concentration. Serum enzyme activities in normal pregnancies (between 20 and 60 muU/ml serum at the end of gestation) were nearly twice as high as those reported by other investigators. In normal single and twin births highest activities were obtained at the expulsion of the placenta which in all cases was followed by a rapid decrease in activity."}
{"id": "PMID:14470", "title": "Glucose-6-phosphate dehydrogenase Velletri.", "content": "A new variant of red cell glucose-6-phosphate dehydrogenase (G6PD) has been found in a Caucasian man with congenital non-spherocytic haemolytic anaemia. This variant has reduced activity, increased thermolability, increased Michaelis constants for glucose-6-phosphate and NADP, slightly increased electrophoretic mobility, and a biphasic pH-activity profile. The red cell adenine compounds and ATP, are in normal limits. The increased activity of red cell NADP-glutathione reductase is probably the expression of a mechanism of compensation for the decrease of G6PD and a consequence of the decrease of NADPH.", "contents": "Glucose-6-phosphate dehydrogenase Velletri. A new variant of red cell glucose-6-phosphate dehydrogenase (G6PD) has been found in a Caucasian man with congenital non-spherocytic haemolytic anaemia. This variant has reduced activity, increased thermolability, increased Michaelis constants for glucose-6-phosphate and NADP, slightly increased electrophoretic mobility, and a biphasic pH-activity profile. The red cell adenine compounds and ATP, are in normal limits. The increased activity of red cell NADP-glutathione reductase is probably the expression of a mechanism of compensation for the decrease of G6PD and a consequence of the decrease of NADPH."}
{"id": "PMID:14471", "title": "Acid-base status before and after arterial clamping.", "content": "The necessity of providing alkalizing therapy after re-establishment of the local circulation was studied in 10 otherwise healthy patients with intermittent claudication. No such necessity was found in providing stable peroperative circulation, normo- to slight hypothermia, adequate infusions, and normal acid-base values prior to arterial clamping. It is pointed out that alkalosis can cause circulatory problems that are just as serious as those occurring with acidosis; therefore the routine use of alkalizing agents during vascular surgery is inadvisable. Should unstable circulatory parameters occur and hypoperfusion be suspected, then repeated control of the acid-base values is indicated.", "contents": "Acid-base status before and after arterial clamping. The necessity of providing alkalizing therapy after re-establishment of the local circulation was studied in 10 otherwise healthy patients with intermittent claudication. No such necessity was found in providing stable peroperative circulation, normo- to slight hypothermia, adequate infusions, and normal acid-base values prior to arterial clamping. It is pointed out that alkalosis can cause circulatory problems that are just as serious as those occurring with acidosis; therefore the routine use of alkalizing agents during vascular surgery is inadvisable. Should unstable circulatory parameters occur and hypoperfusion be suspected, then repeated control of the acid-base values is indicated."}
{"id": "PMID:14472", "title": "The pathogenesis of acute selective necrosis of the granular layer of the human cerebellar cortex.", "content": "PH determinations by means of a sturdy, spear-electrode inserted in the cerebellar tissue immediately after necropsy were carried out in 60 patients suffering from different disorders and dying in hospital, and from 25 individuals killed instantly by violent accidents. A correlation was found between the presence of NGL and low pH levels in the cerebellum (average pH 5.56); subjects without NGL changes showed an average pH OF 6.08. No correlation was found between the pH levels and the time after death, or between pH and any specific disease. The so-called acute selective necrosis of the granular layer of the human cerebellar cortex (NGL), is considered from the present studies to be a phenomenon of postmortem origin. Its relationship to certain specific diseases can be explained by the fact that in these conditions there is a higher postmortem acidity, known to promote autolysis.", "contents": "The pathogenesis of acute selective necrosis of the granular layer of the human cerebellar cortex. PH determinations by means of a sturdy, spear-electrode inserted in the cerebellar tissue immediately after necropsy were carried out in 60 patients suffering from different disorders and dying in hospital, and from 25 individuals killed instantly by violent accidents. A correlation was found between the presence of NGL and low pH levels in the cerebellum (average pH 5.56); subjects without NGL changes showed an average pH OF 6.08. No correlation was found between the pH levels and the time after death, or between pH and any specific disease. The so-called acute selective necrosis of the granular layer of the human cerebellar cortex (NGL), is considered from the present studies to be a phenomenon of postmortem origin. Its relationship to certain specific diseases can be explained by the fact that in these conditions there is a higher postmortem acidity, known to promote autolysis."}
{"id": "PMID:14473", "title": "Infantile periarteritis nodosa or mucocutaneous lymph node syndrome. A report on four cases and diagnostic considerations.", "content": "Coronary artery aneurysm in childhood is a rare disease and has in most cases been ascribed to infantile periarteritis nodosa (IPN). In recent years a mucocutaneous lymph node syndrom (MLNS) has been found almost exclusively in Japan first described by Kawasaki 1967; this disease frequently involves the coronary arteries and myocardium. Four cases with coronary aneurysms are presented from Sweden and seem to be first described from Scandinavia. Three of these patients died a sudden death with cardiac arrest. Since MLNS and IPN have identical clinical and pathological features, we suggest that MLNS and IPN constitute a pathologic entity and that to separate them on a clinical or histological basis is nonsensical. The risk of coronary aneurysm and possible sudden death must be considered in patients with uncharacteristic symptoms including prolonged fever, conjunctivitis, exanthema, lesions in the oral mucosa, elevated sedimintation rate, and leukocytosis.", "contents": "Infantile periarteritis nodosa or mucocutaneous lymph node syndrome. A report on four cases and diagnostic considerations. Coronary artery aneurysm in childhood is a rare disease and has in most cases been ascribed to infantile periarteritis nodosa (IPN). In recent years a mucocutaneous lymph node syndrom (MLNS) has been found almost exclusively in Japan first described by Kawasaki 1967; this disease frequently involves the coronary arteries and myocardium. Four cases with coronary aneurysms are presented from Sweden and seem to be first described from Scandinavia. Three of these patients died a sudden death with cardiac arrest. Since MLNS and IPN have identical clinical and pathological features, we suggest that MLNS and IPN constitute a pathologic entity and that to separate them on a clinical or histological basis is nonsensical. The risk of coronary aneurysm and possible sudden death must be considered in patients with uncharacteristic symptoms including prolonged fever, conjunctivitis, exanthema, lesions in the oral mucosa, elevated sedimintation rate, and leukocytosis."}
{"id": "PMID:14474", "title": "Human interferon and cell growth inhibition. II. Biological and physico-chemical properties of the growth inhibitory component.", "content": "Human leukocyte interferon (IF) inhibits the growth rate of homologous cells in culture. The growth inhibitory component, formerly separated from the antiviral component of human leukocyte IF by adsorption chromatography on albumin-agarose, is investigated. The properties of the component are compared with the accepted characteristics of IF. The growth inhibition is caused by a small molecule, unstable to pH 2 treatment with HCl, but stable to trichloro-acetic acid (TCA) and to proteolytic enzymes. The siolated growth inhibitor seems to be a dimer of molecular weight (mol wt.) approximately 2300. It is activated by heat treatment and lacks species specificity. The discrepancies in the properties of the growth inhibitor before and after separation from IF are discussed.", "contents": "Human interferon and cell growth inhibition. II. Biological and physico-chemical properties of the growth inhibitory component. Human leukocyte interferon (IF) inhibits the growth rate of homologous cells in culture. The growth inhibitory component, formerly separated from the antiviral component of human leukocyte IF by adsorption chromatography on albumin-agarose, is investigated. The properties of the component are compared with the accepted characteristics of IF. The growth inhibition is caused by a small molecule, unstable to pH 2 treatment with HCl, but stable to trichloro-acetic acid (TCA) and to proteolytic enzymes. The siolated growth inhibitor seems to be a dimer of molecular weight (mol wt.) approximately 2300. It is activated by heat treatment and lacks species specificity. The discrepancies in the properties of the growth inhibitor before and after separation from IF are discussed."}
{"id": "PMID:14475", "title": "C1 subcomponents in acute pneumococcal otitis media in children.", "content": "Twenty children with acute pneumococcal otitis media were studied. In 6 children the infection ran a normal course and healed after the first episode and in 14 it relapsed. The serum levels of the immunoglobulins IgG, IgA and IgM were normal in all 20 children. Specific antibodies to pneumococcal polysaccharide were found in all cases, with no differences in the titers between the relapsed cases and those that healed. The complement components were quantitated with electroimmuno assay. G1q proved depressed in 60 per cent of the relapsed cases and in 16 per cent of the healed cases. C1r and C1s were disproportionally high compared with the C1q levels. Furthermore, crossed immunoelectrophoresis revealed abnormal complexes composed of C1r and C1s, and complexes composed of C1r, C1s and C1 IA. These complexes were more pronounced in sera from the children with relapsing otitis media.", "contents": "C1 subcomponents in acute pneumococcal otitis media in children. Twenty children with acute pneumococcal otitis media were studied. In 6 children the infection ran a normal course and healed after the first episode and in 14 it relapsed. The serum levels of the immunoglobulins IgG, IgA and IgM were normal in all 20 children. Specific antibodies to pneumococcal polysaccharide were found in all cases, with no differences in the titers between the relapsed cases and those that healed. The complement components were quantitated with electroimmuno assay. G1q proved depressed in 60 per cent of the relapsed cases and in 16 per cent of the healed cases. C1r and C1s were disproportionally high compared with the C1q levels. Furthermore, crossed immunoelectrophoresis revealed abnormal complexes composed of C1r and C1s, and complexes composed of C1r, C1s and C1 IA. These complexes were more pronounced in sera from the children with relapsing otitis media."}
{"id": "PMID:14477", "title": "Digestive enzymes of three teleost fishes.", "content": "The activity of amylase, sucrase, protease and lipase has been examined in Wallago attu, Clarias batrachus and Labeo rohita. The optimum pH value for carbohydrases ranges from 5.0 to 7.0 and that for trypsin between pH 6.8 and 7.8. Lipase is active at a slightly more alkaline medium. The optimum pH for a given enzyme varies in different sections of the alimentary canal of the same fish and also from species to species. Variations are also found in the optimum substrate concentration for a given enzyme in the different sections of the alimentary canal. The activity of carbohydrases is higher in the herbivorous fish Labeo, than in the carnivorous fish Wallago, and the omnivorous fish Clarias. As for protease, maximum activity is found in Wallago. The difference is not so well marked for the activity of lipase. There is a correlation between the normal diet of the fishes and the relative activity of the digestive enzymes.", "contents": "Digestive enzymes of three teleost fishes. The activity of amylase, sucrase, protease and lipase has been examined in Wallago attu, Clarias batrachus and Labeo rohita. The optimum pH value for carbohydrases ranges from 5.0 to 7.0 and that for trypsin between pH 6.8 and 7.8. Lipase is active at a slightly more alkaline medium. The optimum pH for a given enzyme varies in different sections of the alimentary canal of the same fish and also from species to species. Variations are also found in the optimum substrate concentration for a given enzyme in the different sections of the alimentary canal. The activity of carbohydrases is higher in the herbivorous fish Labeo, than in the carnivorous fish Wallago, and the omnivorous fish Clarias. As for protease, maximum activity is found in Wallago. The difference is not so well marked for the activity of lipase. There is a correlation between the normal diet of the fishes and the relative activity of the digestive enzymes."}
{"id": "PMID:14478", "title": "Myocardial noradrenaline uptake after coronary occlusion in the rat.", "content": "Coronary ligation produced a marked increase in labelled noradrenaline uptake by the myocardial tissue of rats. The peri-ischemic zones showed an elevated accumulation of noradrenaline on the 4th day but the intact zone had returned to normal values. At the 14th day of observation, both the ischemic and per-ischemic tissue exhibited a subnormal accumulation of radioactivity. The role of the acidotic state in the changes of noradrenaline uptake was studied in vitro. Noradrenaline accumulation in the myocardial tissue was higher at pH 6.8 than at 7.4 or 7.1 Competition studies revealed that unlabelled noradrenaline had occupied the binding sites in the same quantity at pH 6.8 and at 7.4. It is assumed that intracellular acidosis was involved in the enhanced accumulation of noradrenaline in the damaged myocardium, and that an increase of noradrenaline concentration in the myocardium may be considered a risk factor in supporting heart function.", "contents": "Myocardial noradrenaline uptake after coronary occlusion in the rat. Coronary ligation produced a marked increase in labelled noradrenaline uptake by the myocardial tissue of rats. The peri-ischemic zones showed an elevated accumulation of noradrenaline on the 4th day but the intact zone had returned to normal values. At the 14th day of observation, both the ischemic and per-ischemic tissue exhibited a subnormal accumulation of radioactivity. The role of the acidotic state in the changes of noradrenaline uptake was studied in vitro. Noradrenaline accumulation in the myocardial tissue was higher at pH 6.8 than at 7.4 or 7.1 Competition studies revealed that unlabelled noradrenaline had occupied the binding sites in the same quantity at pH 6.8 and at 7.4. It is assumed that intracellular acidosis was involved in the enhanced accumulation of noradrenaline in the damaged myocardium, and that an increase of noradrenaline concentration in the myocardium may be considered a risk factor in supporting heart function."}
{"id": "PMID:14481", "title": "Effects of carbachol and calcium on the cyclic guanosine-3',5'-monophosphate (cyclic GMP) metabolism in intestinal smooth muscle.", "content": "In a submaximal concentration carbachol contracted the rabbit colon muscle and increased the cyclic GMP level. The cyclic AMP level was reduced. In a Ca++-depleted muscle carbachol reduced the cyclic GMP level while the effect on the cyclic AMP content of the muscle was unchanged. Carbachol had no effect on the guanylate cyclase activity of the \"plasma membrane fraction\" (the 35-45% fraction). In the homogenate and the microsomal fractions Ca++ had no effect on the guanylate activity while it stimulated the enzyme in a soluble fraction. In the \"plasma membrane fraction\" cyclic GMP released Ca++ from the preloaded fraction and inhibited the Ca++ accumulation. These effects were not found in the vesicular microsomal fraction (the 35% fraction). In both fractions, however, cyclic GMP counteracted the stimulating effect of cyclic AMP. These results indicate that cyclic AMP and GMP may have antagonistic roles on the Ca++ metabolism in the colon muscle. It is suggested that cyclic GMP may act as some kind of positive feedback mechanism which may have a modulating effect on the release of Ca++ from one pool to another in rabbit colon.", "contents": "Effects of carbachol and calcium on the cyclic guanosine-3',5'-monophosphate (cyclic GMP) metabolism in intestinal smooth muscle. In a submaximal concentration carbachol contracted the rabbit colon muscle and increased the cyclic GMP level. The cyclic AMP level was reduced. In a Ca++-depleted muscle carbachol reduced the cyclic GMP level while the effect on the cyclic AMP content of the muscle was unchanged. Carbachol had no effect on the guanylate cyclase activity of the \"plasma membrane fraction\" (the 35-45% fraction). In the homogenate and the microsomal fractions Ca++ had no effect on the guanylate activity while it stimulated the enzyme in a soluble fraction. In the \"plasma membrane fraction\" cyclic GMP released Ca++ from the preloaded fraction and inhibited the Ca++ accumulation. These effects were not found in the vesicular microsomal fraction (the 35% fraction). In both fractions, however, cyclic GMP counteracted the stimulating effect of cyclic AMP. These results indicate that cyclic AMP and GMP may have antagonistic roles on the Ca++ metabolism in the colon muscle. It is suggested that cyclic GMP may act as some kind of positive feedback mechanism which may have a modulating effect on the release of Ca++ from one pool to another in rabbit colon."}
{"id": "PMID:14483", "title": "The analysis of organic water pollutants by gas chromatography and gas chromatography-mass spectrometry.", "content": "Four methods for the analysis of trace levels or organic compounds in water have been discussed: direct aqueous injection, vapor stripping, solvent extraction, and lipophilic adsorption. Table 6 presents a comparison of these techniques. Direct injection is applicable to compounds having a wide range of polarities and volatilities, but it is not a very sensitive technique. For applications in which low sensitivity is acceptable, direct injection offers a very rapid and potentially accurate means of measuring organics in water. Vapor stripping is a factor of 10(6) more sensitive than direct injection, but this is achieved at the expense of simplicity. This method is applicable to compounds of volatilities less than that of eicosane. A subtle operational problem with most vapor stripping techniques is that the contents of the trap are consumed with one analysis; if anything goes awry, the analysis of that trapped sample cannot be repeated. Solvent extraction has a respectable sensitivity (about 0.5 ppb) and operationally it is very simple. Furthermore, aliquots of the resulting extract can be analyzed many times with different techniques if necessary. Because of the evaporation step, very volatile compounds (greater than that of decane) cannot be measured effectively with solvent extraction. The introduction of a solvent into the water carries with it the potential for contamination. Thus, ultrapure solvents must be used and all glassware should be carefully cleaned [96]. Lipophilic adsorption has the unique property of sampling many hundreds of liters of water. Thus, the method is quite sensitive (potentially in the ppt range) and, in addition, it can provide several milligrams of an isolated component. This latter feature is of considerable advantage if one wants to complement GC-MS analyses with infrared or NMR for difficult structural identifications. As a solvent extraction, the evaporation of the final solvent limits the applicability of adsorption methods to compounds with volatilities greater than that of decane. Finally, the importance of avoiding contamination should be emphasized. Many of the compounds encountered in environmental samples are also common laboratory artifacts, for example plasticizers and antioxidants. When one finds such compounds in a water sample, it is absolutely essential to demonstrate that they are indeed present in the water and are not the result of laboratory contamination. The best such demonstration is procedural blank analyses that are indeed blank.", "contents": "The analysis of organic water pollutants by gas chromatography and gas chromatography-mass spectrometry. Four methods for the analysis of trace levels or organic compounds in water have been discussed: direct aqueous injection, vapor stripping, solvent extraction, and lipophilic adsorption. Table 6 presents a comparison of these techniques. Direct injection is applicable to compounds having a wide range of polarities and volatilities, but it is not a very sensitive technique. For applications in which low sensitivity is acceptable, direct injection offers a very rapid and potentially accurate means of measuring organics in water. Vapor stripping is a factor of 10(6) more sensitive than direct injection, but this is achieved at the expense of simplicity. This method is applicable to compounds of volatilities less than that of eicosane. A subtle operational problem with most vapor stripping techniques is that the contents of the trap are consumed with one analysis; if anything goes awry, the analysis of that trapped sample cannot be repeated. Solvent extraction has a respectable sensitivity (about 0.5 ppb) and operationally it is very simple. Furthermore, aliquots of the resulting extract can be analyzed many times with different techniques if necessary. Because of the evaporation step, very volatile compounds (greater than that of decane) cannot be measured effectively with solvent extraction. The introduction of a solvent into the water carries with it the potential for contamination. Thus, ultrapure solvents must be used and all glassware should be carefully cleaned [96]. Lipophilic adsorption has the unique property of sampling many hundreds of liters of water. Thus, the method is quite sensitive (potentially in the ppt range) and, in addition, it can provide several milligrams of an isolated component. This latter feature is of considerable advantage if one wants to complement GC-MS analyses with infrared or NMR for difficult structural identifications. As a solvent extraction, the evaporation of the final solvent limits the applicability of adsorption methods to compounds with volatilities greater than that of decane. Finally, the importance of avoiding contamination should be emphasized. Many of the compounds encountered in environmental samples are also common laboratory artifacts, for example plasticizers and antioxidants. When one finds such compounds in a water sample, it is absolutely essential to demonstrate that they are indeed present in the water and are not the result of laboratory contamination. The best such demonstration is procedural blank analyses that are indeed blank."}
{"id": "PMID:14482", "title": "[Comparison of the effects of oxazepam and oxypertine in treatment of anxious depressive neuroses].", "content": "The author has treated with the double blind method 38 neurotic patients, hysterical or obsessionnal type, in a state of anxious depressive relapse. Some patients received oxazepam (3 X 15 mg per day), others received oxypertine (3X 10 mg per day); this chemotherapy was completed with supportive psychotherapy. Patients were examined at least once a week for one month. At the end of the treatment, results obtained with both drugs were found to be beneficial. Statistical analysis indicates a more both drugs were found to be beneficial. Statistical analysis indicates a more rapid action for oxypertine, which effects are more pronounced than those of the control medication after two weeks of treatment.", "contents": "[Comparison of the effects of oxazepam and oxypertine in treatment of anxious depressive neuroses]. The author has treated with the double blind method 38 neurotic patients, hysterical or obsessionnal type, in a state of anxious depressive relapse. Some patients received oxazepam (3 X 15 mg per day), others received oxypertine (3X 10 mg per day); this chemotherapy was completed with supportive psychotherapy. Patients were examined at least once a week for one month. At the end of the treatment, results obtained with both drugs were found to be beneficial. Statistical analysis indicates a more both drugs were found to be beneficial. Statistical analysis indicates a more rapid action for oxypertine, which effects are more pronounced than those of the control medication after two weeks of treatment."}
{"id": "PMID:14485", "title": "Renin and age as determinants of a predominantly betablocker-based antihypertensive drug program.", "content": "Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%) or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall in two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of betablocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, betablockers normalized blood pressure (less than or equal to 95 mm Hg diastolic) in three-quarters of the younger-than-40-year-olds, in about half of those 40-60 years of age but in only 20% of those over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state whereas those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the betablockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, although not exclusively, to renin suppression.", "contents": "Renin and age as determinants of a predominantly betablocker-based antihypertensive drug program. Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%) or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall in two categories: younger patients with fairly mild hypertension and older patients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of betablocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, betablockers normalized blood pressure (less than or equal to 95 mm Hg diastolic) in three-quarters of the younger-than-40-year-olds, in about half of those 40-60 years of age but in only 20% of those over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state whereas those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the betablockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, although not exclusively, to renin suppression."}
{"id": "PMID:14490", "title": "The importance of bites by the saw-scaled or carpet viper (Echis carinatus): epidemiological studies in Nigeria and a review of the world literature.", "content": "The incidence of Echis carinatus (saw-scaled or carpet viper) bite and its mortality have been investigated in the Nigerian savanna region. A geographical area was defined in which the snake was particularly abundant and bites were frequent. Perennial and seasonal fluctuations in incidence and mortality, the circumstances in which bites occurred and the types of people bitten were studied at Bambur, Zaria, Kaltungo and Gombe hospitals. Peak incidence coincided with the increase in farming during the rains whereas percentage mortality seemed to be greatest during the cold dry season. The majority of the patients were young males bitten on the foot while walking or farming. A review of the world literature indicated that E. carinatus was the principal cause of snake bite morbidity wherever data were available throughout its wide geographical range. Official statistics have seriously underestimated this important rural health problem.", "contents": "The importance of bites by the saw-scaled or carpet viper (Echis carinatus): epidemiological studies in Nigeria and a review of the world literature. The incidence of Echis carinatus (saw-scaled or carpet viper) bite and its mortality have been investigated in the Nigerian savanna region. A geographical area was defined in which the snake was particularly abundant and bites were frequent. Perennial and seasonal fluctuations in incidence and mortality, the circumstances in which bites occurred and the types of people bitten were studied at Bambur, Zaria, Kaltungo and Gombe hospitals. Peak incidence coincided with the increase in farming during the rains whereas percentage mortality seemed to be greatest during the cold dry season. The majority of the patients were young males bitten on the foot while walking or farming. A review of the world literature indicated that E. carinatus was the principal cause of snake bite morbidity wherever data were available throughout its wide geographical range. Official statistics have seriously underestimated this important rural health problem."}
{"id": "PMID:14491", "title": "Etiological determinants of protein calorie undernutrition in a rural child community.", "content": "Two groups of randomly selected underweight and well-nourished preschool children residing in study villages of Punjab, Ludhiana district were examined with respect to their socioeconomic background, birth weights, dietary intakes, quality of received mother care, blood biochemistry, parasite load, psychomotor development and past illness prevalence. It was found that underweight children showed significantly less favourable indices in all of the above categories except stool parasitology suggesting an extremely intricate and complex interaction of a host of ecological variables in the causation of undernutrition. Using the discriminate analysis on readily available social variables, it was found that caste affiliation and, less so parental income were the two most significant variables distinguishing between the two groups. A model for the interaction patterns of ecological variables in their effect of protein calorie malnutrition for the given area is suggested.", "contents": "Etiological determinants of protein calorie undernutrition in a rural child community. Two groups of randomly selected underweight and well-nourished preschool children residing in study villages of Punjab, Ludhiana district were examined with respect to their socioeconomic background, birth weights, dietary intakes, quality of received mother care, blood biochemistry, parasite load, psychomotor development and past illness prevalence. It was found that underweight children showed significantly less favourable indices in all of the above categories except stool parasitology suggesting an extremely intricate and complex interaction of a host of ecological variables in the causation of undernutrition. Using the discriminate analysis on readily available social variables, it was found that caste affiliation and, less so parental income were the two most significant variables distinguishing between the two groups. A model for the interaction patterns of ecological variables in their effect of protein calorie malnutrition for the given area is suggested."}
{"id": "PMID:14492", "title": "Salivary Secretion in wild Glossina pallidipes Austen. (Diptera, Glossinidae).", "content": "The salivation behaviour of wild G. pallidipes obtained from Lambwe Valley and Kbwezi was studied. Salivation was measured by counting the number of salivary drops secreted per minute and measuring the sizes of the stained saliva after drawing them with a camera lucida. The results confirmed observations obtained from laboratory bred flies. The quantity of saliva secreted by tsetse flies was significantly increased as the flies became hungrier. The proportion of flies salivating also increased with intensity of hunger. Female G. pallidipes secreted significantly more saliva than the males. There was no significant difference between the quantities of saliva secreted by infected and free tsetse flies; thus there is no evidence to support the suggestion that the presence of trypanosomes in the tsetse fly stimulated it to salivate copiously. Flies having trypanosome infection in their salivary glands discharge large numbers of mature parasites in their saliva. Flies with trypanosomes in their proboscis discharged relatively few mature and immature parasites in their saliva.", "contents": "Salivary Secretion in wild Glossina pallidipes Austen. (Diptera, Glossinidae). The salivation behaviour of wild G. pallidipes obtained from Lambwe Valley and Kbwezi was studied. Salivation was measured by counting the number of salivary drops secreted per minute and measuring the sizes of the stained saliva after drawing them with a camera lucida. The results confirmed observations obtained from laboratory bred flies. The quantity of saliva secreted by tsetse flies was significantly increased as the flies became hungrier. The proportion of flies salivating also increased with intensity of hunger. Female G. pallidipes secreted significantly more saliva than the males. There was no significant difference between the quantities of saliva secreted by infected and free tsetse flies; thus there is no evidence to support the suggestion that the presence of trypanosomes in the tsetse fly stimulated it to salivate copiously. Flies having trypanosome infection in their salivary glands discharge large numbers of mature parasites in their saliva. Flies with trypanosomes in their proboscis discharged relatively few mature and immature parasites in their saliva."}
{"id": "PMID:14494", "title": "Nuclear coat and viruslike particles in the midgut epithelium of Glossina morsitans sspp.", "content": "The ultrastructural aspects of the nuclear coat formation in midgut epithelial cells of pupae and adult flies of G. morsitans sspp. are described. Out of four different species of Glossina examined, this peculiar structure was only found in G. morsitans sspp. Three different types of viruslike particles were found in midgut epithelial cells. One type which is of the same kind of particle found in the salivary glands, lies inside of cytoplasmic vesicles. Two other types of particles were detected in the nuclei.", "contents": "Nuclear coat and viruslike particles in the midgut epithelium of Glossina morsitans sspp. The ultrastructural aspects of the nuclear coat formation in midgut epithelial cells of pupae and adult flies of G. morsitans sspp. are described. Out of four different species of Glossina examined, this peculiar structure was only found in G. morsitans sspp. Three different types of viruslike particles were found in midgut epithelial cells. One type which is of the same kind of particle found in the salivary glands, lies inside of cytoplasmic vesicles. Two other types of particles were detected in the nuclei."}
{"id": "PMID:14496", "title": "Comparative study of the postoperative flow in the saphenous vein and internal mammary artery bypass grafts.", "content": "Postoperative coronary bypass flow was evaluated in two groups of randomly selected patients with grafts to the left anterior descending artery (LAD). Saphenous vein bypass grafts were placed in 27 patients and internal mammary artery grafts in 25 patients. Postoperative flow studies were performed in both groups with roentgendensitometric methods based on the transit time of radiopaque media along the graft plus the mean graft diameter. There was no significant difference between the two groups of patients for age, duration of symptoms, or the frequency of hypertension, diabetes mellitus, prior myocardial infarction, or cardiomegaly. Intraoperative bypass flows were 75+/-27 and 77+/-24 ml. per minute for the saphenous vein group (SVG) and internal mammary artery group (IMAG), respectively. There was no significant difference in the heart rate or mean aortic pressure at the time of the roentgendensitometric flow study. The mean graft diameters were 3.0+/-0.5 and 1.9+/-0.3 mm. for the SVG and IMAG, respectively (p less than 0.001). The ratios of graft diameter to LAD diameter were 1.9+/-0.3 and 1.2+/-0.2 for the SVG and IMAG, respectively (p less than 0.001). The roentgendensitometric postoperative flows were 68+/-27 ml. per minute in the SVG and 46+/-16 ml. per minute in the IMAG (p less than 0.01). The present study indicates that flow in significantly higher in saphenous vein than in internal mammary artery bypasses and that the difference in flow may in part be explained on the basis of the graft diameter.", "contents": "Comparative study of the postoperative flow in the saphenous vein and internal mammary artery bypass grafts. Postoperative coronary bypass flow was evaluated in two groups of randomly selected patients with grafts to the left anterior descending artery (LAD). Saphenous vein bypass grafts were placed in 27 patients and internal mammary artery grafts in 25 patients. Postoperative flow studies were performed in both groups with roentgendensitometric methods based on the transit time of radiopaque media along the graft plus the mean graft diameter. There was no significant difference between the two groups of patients for age, duration of symptoms, or the frequency of hypertension, diabetes mellitus, prior myocardial infarction, or cardiomegaly. Intraoperative bypass flows were 75+/-27 and 77+/-24 ml. per minute for the saphenous vein group (SVG) and internal mammary artery group (IMAG), respectively. There was no significant difference in the heart rate or mean aortic pressure at the time of the roentgendensitometric flow study. The mean graft diameters were 3.0+/-0.5 and 1.9+/-0.3 mm. for the SVG and IMAG, respectively (p less than 0.001). The ratios of graft diameter to LAD diameter were 1.9+/-0.3 and 1.2+/-0.2 for the SVG and IMAG, respectively (p less than 0.001). The roentgendensitometric postoperative flows were 68+/-27 ml. per minute in the SVG and 46+/-16 ml. per minute in the IMAG (p less than 0.01). The present study indicates that flow in significantly higher in saphenous vein than in internal mammary artery bypasses and that the difference in flow may in part be explained on the basis of the graft diameter."}
{"id": "PMID:14498", "title": "The essential action of propranolol in hypertension.", "content": "The unique action of propranolol and other beta blockers in lowering raised arterial pressure is discussed. Although the onset of the antihypertensive effect is not immediate, many trials have confirmed the efficacy of these drugs. Animal experiments have thrown little light on the mechanism of action of beta blockers in hypertension: this may be because in animals, especially the rat, peripheral beta adrenoceptor vasodilatation is relatively more important than in man. Five principal theories have been advanced to explain the antihypertensive effect. None of these, the renin, central nervous system, cardiac, baroceptor or metabolite theory, is totally satisfactory. A new theory is proposed suggesting that the essential action is to diminish sympathetic nerve output by damping sensory input to the central nervous system from a heart whose capacity to respond to exercise and stress is blunted by beta adrenoceptor blockade.", "contents": "The essential action of propranolol in hypertension. The unique action of propranolol and other beta blockers in lowering raised arterial pressure is discussed. Although the onset of the antihypertensive effect is not immediate, many trials have confirmed the efficacy of these drugs. Animal experiments have thrown little light on the mechanism of action of beta blockers in hypertension: this may be because in animals, especially the rat, peripheral beta adrenoceptor vasodilatation is relatively more important than in man. Five principal theories have been advanced to explain the antihypertensive effect. None of these, the renin, central nervous system, cardiac, baroceptor or metabolite theory, is totally satisfactory. A new theory is proposed suggesting that the essential action is to diminish sympathetic nerve output by damping sensory input to the central nervous system from a heart whose capacity to respond to exercise and stress is blunted by beta adrenoceptor blockade."}
{"id": "PMID:14499", "title": "Acute and long-term studies of the mechanisms of action of beta-blocking drugs in lowering blood pressure.", "content": "The antihypertensive effect of intravenous (acute) and oral (long-term) beta-adrenergic blockade with propranolol or pindolol was evaluated in 46 male patients with either borderline (group I; 23 patients) or sustained (group II; 23 patients) essential hypertension. Arterial pressure, plasma renin activity and plasma concentration of aldosterone were determined during continuous recumbency overnight every 30 minutes before and after treatment. Patients of group I exhibited a marked variation of their recumbent plasma renin activity with relatively low values before midnight and large increases early in the morning. In contrast, low plasma renin activity values and only minimal fluctuations in renin were observed in patients of group II. Plasma renin activity had a consistent relationship with blood pressure both after acute (r = 0.79) and long-term (r = 0.4) beta-blockade. In four patients of group I, who had high plasma renin activity and had responded to intravenous propranolol, infusion of angiotensin II inhibitor did not lower pressure. In group I following beta-blockade, day-night profiles of renin were similar to those observed in group II before treatment. Thus in this latter subgroup, low renin profiles might reflect reduced beta-adrenergic activity. Acute as well as long-term beta-blockade consistently eliminated the day-night rhythm of plasma renin activity, but it did not change rhythm of plasma concentration of aldosterone. Plasma concentration of aldosterone was lower in group II but appeared to be inappropriately high relative to renin levels. These observations suggest that in hypertensive patients classified according to blood pressure and recumbent plasma renin activity profiles a significant relationship exists between changes in plasma renin activity and arterial pressure responses. Thus, patients with high renin levels respond better to treatment than patients with low renin levels. We conclude that in the patients studied, sympathetic nervous system activity mainly determined renin levels as well as antihypertensive effectiveness of the beta-blocking drugs.", "contents": "Acute and long-term studies of the mechanisms of action of beta-blocking drugs in lowering blood pressure. The antihypertensive effect of intravenous (acute) and oral (long-term) beta-adrenergic blockade with propranolol or pindolol was evaluated in 46 male patients with either borderline (group I; 23 patients) or sustained (group II; 23 patients) essential hypertension. Arterial pressure, plasma renin activity and plasma concentration of aldosterone were determined during continuous recumbency overnight every 30 minutes before and after treatment. Patients of group I exhibited a marked variation of their recumbent plasma renin activity with relatively low values before midnight and large increases early in the morning. In contrast, low plasma renin activity values and only minimal fluctuations in renin were observed in patients of group II. Plasma renin activity had a consistent relationship with blood pressure both after acute (r = 0.79) and long-term (r = 0.4) beta-blockade. In four patients of group I, who had high plasma renin activity and had responded to intravenous propranolol, infusion of angiotensin II inhibitor did not lower pressure. In group I following beta-blockade, day-night profiles of renin were similar to those observed in group II before treatment. Thus in this latter subgroup, low renin profiles might reflect reduced beta-adrenergic activity. Acute as well as long-term beta-blockade consistently eliminated the day-night rhythm of plasma renin activity, but it did not change rhythm of plasma concentration of aldosterone. Plasma concentration of aldosterone was lower in group II but appeared to be inappropriately high relative to renin levels. These observations suggest that in hypertensive patients classified according to blood pressure and recumbent plasma renin activity profiles a significant relationship exists between changes in plasma renin activity and arterial pressure responses. Thus, patients with high renin levels respond better to treatment than patients with low renin levels. We conclude that in the patients studied, sympathetic nervous system activity mainly determined renin levels as well as antihypertensive effectiveness of the beta-blocking drugs."}
{"id": "PMID:14500", "title": "Renin and aldosterone secretion in pheochromocytoma. Effect of chronic alpha-adrenergic receptor blockade.", "content": "Patients suffering from pheochromocytoma characterized by an exclusive or almost exclusive excess of norepinephrine showed no (one patient) or only a moderate increase (two patients) in renin and aldosterone secretion. In those three patients with concomitant distinct hypersecretion of epinephrine, renin release (and aldosterone secretion except in one patient) was markedly enhanced. Similar results were obtained in a patient with excess norepinephrine and dopamine secretion. Renin release was markedly reduced in all patients during preoperative long-term alpha-adrenergic receptor blockade. With the exception of one patient, increased renin and aldosterone secretion was abolished. The results indicate that augmentation in renin release depends on the ratio of the different catecholamines secreted by the pheochromocytoma and their different effe-tiveness in stimulating beta-adrenergic receptors. Even in the presence of excess catecholamine secretion, there is evidence that renin secretion is predominantly mediated by beta receptors rather than by renal vascular alpha-adrenergic receptors. Normalization of catecholamine-induced enhanced renin release in patients with pheochromocytoma during chronic alpha-adrenergic receptor blockade supports the assumption that (alpha-) adrenergic blocking agents inhibit renin secretion distal to their blockade of specific adrenergic receptors. However, contrary to beta-adrenergic blockade, circadian rhythm of renin release seems to remain intact during alpha-adrenergic blockade.", "contents": "Renin and aldosterone secretion in pheochromocytoma. Effect of chronic alpha-adrenergic receptor blockade. Patients suffering from pheochromocytoma characterized by an exclusive or almost exclusive excess of norepinephrine showed no (one patient) or only a moderate increase (two patients) in renin and aldosterone secretion. In those three patients with concomitant distinct hypersecretion of epinephrine, renin release (and aldosterone secretion except in one patient) was markedly enhanced. Similar results were obtained in a patient with excess norepinephrine and dopamine secretion. Renin release was markedly reduced in all patients during preoperative long-term alpha-adrenergic receptor blockade. With the exception of one patient, increased renin and aldosterone secretion was abolished. The results indicate that augmentation in renin release depends on the ratio of the different catecholamines secreted by the pheochromocytoma and their different effe-tiveness in stimulating beta-adrenergic receptors. Even in the presence of excess catecholamine secretion, there is evidence that renin secretion is predominantly mediated by beta receptors rather than by renal vascular alpha-adrenergic receptors. Normalization of catecholamine-induced enhanced renin release in patients with pheochromocytoma during chronic alpha-adrenergic receptor blockade supports the assumption that (alpha-) adrenergic blocking agents inhibit renin secretion distal to their blockade of specific adrenergic receptors. However, contrary to beta-adrenergic blockade, circadian rhythm of renin release seems to remain intact during alpha-adrenergic blockade."}
{"id": "PMID:14501", "title": "Experience with pindolol, a betareceptor blocker, in the treatment of hypertension.", "content": "Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance.", "contents": "Experience with pindolol, a betareceptor blocker, in the treatment of hypertension. Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance."}
{"id": "PMID:14502", "title": "Beta-adrenoreceptor blockade in hypertension.", "content": "There is good evidence from many sources that beta-adrenoreceptor blockade is an effective form of therapy in mild, moderate and severe hypertension either alone or in combination with other antihypertensive agents. Although a number os such beta blocking compounds are now available, they appear to have a hypotensive effect of approximately equal magnitude. This hypotensive effect is obtained in both the supine and standing positions thus avoiding postural hypotension. The maximum hypotensive effect may take some time to become apparent. Despite considerable work the mode of action remains uncertain, reduction in cardiac output, resetting of baroreceptors, reduction in plasma renin and a central nervous system effect have been suggested but remain unproved. There is evidence to suggest that these compounds can control, to some degree, the surges in blood pressure resulting from either mental or physical stress. A low incidence of serious side effects has been reported by many workers. Only the long-term use of these compounds in comparison with other antihypertensive agents will determine their place in the management of hypertension.", "contents": "Beta-adrenoreceptor blockade in hypertension. There is good evidence from many sources that beta-adrenoreceptor blockade is an effective form of therapy in mild, moderate and severe hypertension either alone or in combination with other antihypertensive agents. Although a number os such beta blocking compounds are now available, they appear to have a hypotensive effect of approximately equal magnitude. This hypotensive effect is obtained in both the supine and standing positions thus avoiding postural hypotension. The maximum hypotensive effect may take some time to become apparent. Despite considerable work the mode of action remains uncertain, reduction in cardiac output, resetting of baroreceptors, reduction in plasma renin and a central nervous system effect have been suggested but remain unproved. There is evidence to suggest that these compounds can control, to some degree, the surges in blood pressure resulting from either mental or physical stress. A low incidence of serious side effects has been reported by many workers. Only the long-term use of these compounds in comparison with other antihypertensive agents will determine their place in the management of hypertension."}
{"id": "PMID:14503", "title": "Rapid identification of patients with essential hypertension sensitive to acebutolol (a new cardioselective beta-blocker).", "content": "Acebutolol, a new cardioselective beta-blocking agent, was administered for 48 hours to 44 patients with essential hypertension at a total dosage of 2.0 g (2,000 mg). The slowing down of their pulse rate and the decrease in blood pressure were highly significant, whereas eight subjects treated with placebos had no change in either the pulse rate or blood pressure. Plasma renin activity decreased from 2.26 +/- 2.11 ng/ml/hour to 0.87 +/- 1.04 ng/ml/hour. The decrease in blood pressure was correlated with the initial plasma renin activity and with the decrease in plasma renin activity. These results demonstrate that a rapid decrease in blood pressure can be obtained in patients with essential hypertension treated with acebutolol and that the decrease in blood pressure is related to the initial state of the renin-angiotensin system.", "contents": "Rapid identification of patients with essential hypertension sensitive to acebutolol (a new cardioselective beta-blocker). Acebutolol, a new cardioselective beta-blocking agent, was administered for 48 hours to 44 patients with essential hypertension at a total dosage of 2.0 g (2,000 mg). The slowing down of their pulse rate and the decrease in blood pressure were highly significant, whereas eight subjects treated with placebos had no change in either the pulse rate or blood pressure. Plasma renin activity decreased from 2.26 +/- 2.11 ng/ml/hour to 0.87 +/- 1.04 ng/ml/hour. The decrease in blood pressure was correlated with the initial plasma renin activity and with the decrease in plasma renin activity. These results demonstrate that a rapid decrease in blood pressure can be obtained in patients with essential hypertension treated with acebutolol and that the decrease in blood pressure is related to the initial state of the renin-angiotensin system."}
{"id": "PMID:14504", "title": "Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.", "content": "The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.", "contents": "Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension. The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents."}
{"id": "PMID:14505", "title": "Gastric emptying and secretion in the rhesus monkey.", "content": "The volume and composition of the gastric contents as well as the rates of gastric emptying and secretion were determined simultaneously in conscious chair-adapted monkeys. These determinations were made during fasting and after a liquid meal, thereby allowing studies of the physiologic variables which regulate gastric emptying and gastric secretion. Administration of a water meal is followed by a complex pattern of changes in rates of secretion as well as the fractional rate of emptying. During administration of a 100-ml water meal (pH 7.4), intragastric volume increased while acid concentration decreased; both then returned to fasting values 50 min later. The fractional rate of emptying increased fivefold during administration of the water meal, returned to basal values after 30 min, and then increased again, indicating that gastric emptying cannot be characterized as a simple first-order process with a constant coefficient. The pattern of the change in the rate of water secretion was similar to that for fractional gastric emptying. In contrast, after the meal, gastric acid secretion increased steadily and did not become maximal until 20 min.", "contents": "Gastric emptying and secretion in the rhesus monkey. The volume and composition of the gastric contents as well as the rates of gastric emptying and secretion were determined simultaneously in conscious chair-adapted monkeys. These determinations were made during fasting and after a liquid meal, thereby allowing studies of the physiologic variables which regulate gastric emptying and gastric secretion. Administration of a water meal is followed by a complex pattern of changes in rates of secretion as well as the fractional rate of emptying. During administration of a 100-ml water meal (pH 7.4), intragastric volume increased while acid concentration decreased; both then returned to fasting values 50 min later. The fractional rate of emptying increased fivefold during administration of the water meal, returned to basal values after 30 min, and then increased again, indicating that gastric emptying cannot be characterized as a simple first-order process with a constant coefficient. The pattern of the change in the rate of water secretion was similar to that for fractional gastric emptying. In contrast, after the meal, gastric acid secretion increased steadily and did not become maximal until 20 min."}
{"id": "PMID:14506", "title": "Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs.", "content": "When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired.", "contents": "Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs. When the administration of exogenous mineralocorticoid hormones was discontinued in adrenalectomized dogs maintained on glucocorticoid, net acid excretion decreased due largely to a reduction in urinary ammonium excretion (UNH4+V), and hyperchloremic hyperkalemic metabolic acidosis occurred and persisted. The reduction in UNH4+V was not associated with an increase in urine pH (UpH) or a decrease in urine flow, but correlated with the severity of hyperkalemia and was mitigated by dietary potassium restriction. UpH decreased to values as low as 5.3. During acidosis, UpH varied directly with UNH4+V, but in relation to UNH4+V, UpH exceeded that in acid-fed mineralocorticoid-replete dogs. Extrapolated to UNH4+V=0, however, UpH was not significantly different in the two groups (5.27 vs. 5.44). When distal delivery of sodium was increased by infusion of sodium phosphate, titratable acid excretion increased in both groups but pateaued at lower rates in the mineralocorticoid-deficient dogs. These results suggest that in mineralocorticoid-deficient dogs, renal ammonia production is diminished, in part due to potassium retention and hyperkalemia; renal hydrogen ion secretory capacity is reduced even when sodium and buffer delivery to the distal nephron is not reduced; and the ability of the kidney to generate normally steep urine-to-blood hydrogen ion concentration gradients is unimpaired."}
{"id": "PMID:14507", "title": "Mechanism of intrarenal blood flow redistribution after carotid artery occlusion.", "content": "Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.", "contents": "Mechanism of intrarenal blood flow redistribution after carotid artery occlusion. Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity."}
{"id": "PMID:14508", "title": "A smooth muscle active factor isolated from renal cortex of the rabbit.", "content": "Homogenates of rabbit renal cortex contained a water-soluble material with striking activity on smooth muscle derived from the rabbit aorta, rat stomach, and guinea pig ileum--but not rat colon or chick rectum. Evidence derived from the spectrum of its pharmacologic activity, the influence of specific competitive antagonists on the smooth muscle responses to the factor, the influence of proteolytic enzymes and its elution position during molecular sieve filtration on Sephadex G-10 made it unlikely that the factor was a prostaglandin, renin, angiotensin, a catecholamine, serotonin, bradykinin, a nucleotide, a small organic product of local metabolism, or a small ion. The agent was not found in extracts of renal medulla, spleen, myocardium, or lung. The smooth muscle response to the factor was blocked by phenoxybenzamine. The renal cortical factor in subthreshold concentration also potentiated responses of the rabbit aorta to angiotensin and norepinephrine. The factor's intrinsic activity and ability to potentiate the smooth muscle actions of endogenous vasoconstrictors make it a candidate as a mediator of smooth muscle responses in a number of states.", "contents": "A smooth muscle active factor isolated from renal cortex of the rabbit. Homogenates of rabbit renal cortex contained a water-soluble material with striking activity on smooth muscle derived from the rabbit aorta, rat stomach, and guinea pig ileum--but not rat colon or chick rectum. Evidence derived from the spectrum of its pharmacologic activity, the influence of specific competitive antagonists on the smooth muscle responses to the factor, the influence of proteolytic enzymes and its elution position during molecular sieve filtration on Sephadex G-10 made it unlikely that the factor was a prostaglandin, renin, angiotensin, a catecholamine, serotonin, bradykinin, a nucleotide, a small organic product of local metabolism, or a small ion. The agent was not found in extracts of renal medulla, spleen, myocardium, or lung. The smooth muscle response to the factor was blocked by phenoxybenzamine. The renal cortical factor in subthreshold concentration also potentiated responses of the rabbit aorta to angiotensin and norepinephrine. The factor's intrinsic activity and ability to potentiate the smooth muscle actions of endogenous vasoconstrictors make it a candidate as a mediator of smooth muscle responses in a number of states."}
{"id": "PMID:14509", "title": "Specific desensitization (tachyphylaxis) of the guinea pig ileum to angiotensin II.", "content": "Tachyphylaxis to [Ile5]angiotensin II (angiotensin) in the isolated guinea pig ileum was found to be more severe when the Ca2+ concentration or the temperature of the medium were lowered, or when glucose was absent. Incubation with indomethacin or prostaglandin E2 did not affect the onset of tachyphylaxis or recovery from the tachyphylactic state. The angiotensin dose-response curves of tachyphylactic organs were shifted to the right, and the maximum responses were depressed in proportion to the conditioning doses of the hormone. The recovery from tachyphylaxis followed zero-order kinetics and was not affected by Ca2+ concentration or pH. The temperature dependence of the rate of recovery yielded a value of 14.6 kcal/mol for the activation energy in the physiological temperature range. It is concluded that tachyphylaxis results from the tight binding of angiotensin to superficial calcium-binding sites in the smooth muscle cell membrane. Recovery from tachyphylaxis appears to involve displacement of angiotensin by calcium in a process that is dependent on active transport.", "contents": "Specific desensitization (tachyphylaxis) of the guinea pig ileum to angiotensin II. Tachyphylaxis to [Ile5]angiotensin II (angiotensin) in the isolated guinea pig ileum was found to be more severe when the Ca2+ concentration or the temperature of the medium were lowered, or when glucose was absent. Incubation with indomethacin or prostaglandin E2 did not affect the onset of tachyphylaxis or recovery from the tachyphylactic state. The angiotensin dose-response curves of tachyphylactic organs were shifted to the right, and the maximum responses were depressed in proportion to the conditioning doses of the hormone. The recovery from tachyphylaxis followed zero-order kinetics and was not affected by Ca2+ concentration or pH. The temperature dependence of the rate of recovery yielded a value of 14.6 kcal/mol for the activation energy in the physiological temperature range. It is concluded that tachyphylaxis results from the tight binding of angiotensin to superficial calcium-binding sites in the smooth muscle cell membrane. Recovery from tachyphylaxis appears to involve displacement of angiotensin by calcium in a process that is dependent on active transport."}
{"id": "PMID:14510", "title": "Effect of nicotine on gastric acid secretion: evidence of electrogenic pump theory.", "content": "In vitro studies on H+ secretion, potential difference (PD), short-circuit current (Isc), and resistance across stripped mucosa of frog stomach in Cl-medium have shown that addition of nicotine in the serum bathing fluid caused a marked inhibition of the H+ secretory rate and an increase of PD and Isc without change of the transmucosal resistance. A dose-response correlation was indicated. During the first 8 min, the changes in the measured parameters, namely, PD versus Ih and Isc versus Ih, were linear. After 8 min, a deviation from linearity was observed. From the slope of the regression lines, the resistance of the electrogenic Cl- pump on the mucosal membrane (Rcl) was calculated to be 127 omega cm2 and the resistance of the chloride pathway on the serosal side (Rcl) was 407 omega cm2. The resistance of the H+ pump on the mucosal membrane (Rh) in Cl- medium was estimated to be  385 omega cm2. The sum of the emf's of the Cl+ pump on the mucosal membrane and of the Cl- gradient across the serosal membrane, namely Ecl + Ecl, was found to be 35 mV. The presence of such linear relationships between measured versus the H+ rate and Isc versus Ih lends support to the electrogenic theory of HCl secretion.", "contents": "Effect of nicotine on gastric acid secretion: evidence of electrogenic pump theory. In vitro studies on H+ secretion, potential difference (PD), short-circuit current (Isc), and resistance across stripped mucosa of frog stomach in Cl-medium have shown that addition of nicotine in the serum bathing fluid caused a marked inhibition of the H+ secretory rate and an increase of PD and Isc without change of the transmucosal resistance. A dose-response correlation was indicated. During the first 8 min, the changes in the measured parameters, namely, PD versus Ih and Isc versus Ih, were linear. After 8 min, a deviation from linearity was observed. From the slope of the regression lines, the resistance of the electrogenic Cl- pump on the mucosal membrane (Rcl) was calculated to be 127 omega cm2 and the resistance of the chloride pathway on the serosal side (Rcl) was 407 omega cm2. The resistance of the H+ pump on the mucosal membrane (Rh) in Cl- medium was estimated to be  385 omega cm2. The sum of the emf's of the Cl+ pump on the mucosal membrane and of the Cl- gradient across the serosal membrane, namely Ecl + Ecl, was found to be 35 mV. The presence of such linear relationships between measured versus the H+ rate and Isc versus Ih lends support to the electrogenic theory of HCl secretion."}
{"id": "PMID:14511", "title": "Consequences of ventromedial hypothalamic lesions on metabolism of perfused rat liver.", "content": "Metabolism of perfused livers from control and ventromedial hypothalamus (VMH)-lesioned rats has been studied. To eliminate the possibility that observed metabolic abnormalities could be realted to hyperphagia, VMH-lesioned rats were placed on restricted diet matching that of controls. Ten days postoperatively, VMH-lesioned rats had hyperinsulinemia, hypertriglyceridemia, increased blood urea nitrogen levels, together with decreased plasma free fatty acid (FFA) and glucose levels. Insulin release produced in vivo by a glucose load was much higher in VMH-lesioned than in control rats. Perfused livers from VMH-lesioned rats secreted more triglycerides and produced more urea than controls, whereas production of glucose and ketone bodies was reduced. Lipogenesis, newly synthesized triglyceride secretion, and the activity of acetyl-CoA carboxylase and fatty acid synthetase were greatest in livers from VMH-lesioned rats. Fasting abolished hyperinsulinemia and most of these observed metabolic alterations. After treatment with anti-insulin serum, the high rate of lipogenesis observed in livers from VMH-lesioned rats was restored toward normal. It is suggested that hyperinsulinemia may be partly responsible for the metabolic disorders observed in livers from nonhyperphagic VMH-lesioned rats.", "contents": "Consequences of ventromedial hypothalamic lesions on metabolism of perfused rat liver. Metabolism of perfused livers from control and ventromedial hypothalamus (VMH)-lesioned rats has been studied. To eliminate the possibility that observed metabolic abnormalities could be realted to hyperphagia, VMH-lesioned rats were placed on restricted diet matching that of controls. Ten days postoperatively, VMH-lesioned rats had hyperinsulinemia, hypertriglyceridemia, increased blood urea nitrogen levels, together with decreased plasma free fatty acid (FFA) and glucose levels. Insulin release produced in vivo by a glucose load was much higher in VMH-lesioned than in control rats. Perfused livers from VMH-lesioned rats secreted more triglycerides and produced more urea than controls, whereas production of glucose and ketone bodies was reduced. Lipogenesis, newly synthesized triglyceride secretion, and the activity of acetyl-CoA carboxylase and fatty acid synthetase were greatest in livers from VMH-lesioned rats. Fasting abolished hyperinsulinemia and most of these observed metabolic alterations. After treatment with anti-insulin serum, the high rate of lipogenesis observed in livers from VMH-lesioned rats was restored toward normal. It is suggested that hyperinsulinemia may be partly responsible for the metabolic disorders observed in livers from nonhyperphagic VMH-lesioned rats."}
{"id": "PMID:14512", "title": "Uptake of K+ by frog gastric mucosa from submucosal side and acid secretory rate.", "content": "The K+ content in frog gastric mucosa (K+) was measured as a function of the submucosal K+ concentration ([K+sm]) in the absence of K+ on the mucosal side. The (K+) in HCO3- buffer with 95% O2-5% CO2 gas showed that the removal of external K+ induced a  27% K+ loss from the control value of 5 mM K+sm, that there was no linear relation between (K+) and [K+sm, and that the change in the (K+) versus the [K+sm] was hyperbolic, indicating that there are two different types of K+ in the mucosa: bound and free K+.", "contents": "Uptake of K+ by frog gastric mucosa from submucosal side and acid secretory rate. The K+ content in frog gastric mucosa (K+) was measured as a function of the submucosal K+ concentration ([K+sm]) in the absence of K+ on the mucosal side. The (K+) in HCO3- buffer with 95% O2-5% CO2 gas showed that the removal of external K+ induced a  27% K+ loss from the control value of 5 mM K+sm, that there was no linear relation between (K+) and [K+sm, and that the change in the (K+) versus the [K+sm] was hyperbolic, indicating that there are two different types of K+ in the mucosa: bound and free K+."}
{"id": "PMID:14513", "title": "Intracellular pH in hypoxic smooth muscle.", "content": "Hypoxia impairs contractility in canine tracheal smooth muscle (TSM). This is attributed to intracellular lactacidosis. The present studies were undertaken to confirm this. Lactate was found to be significantly increased in hypoxic TSM (65.36 +/- 7.37 mg/100 g wet tissue), compared to normoxic (29.83 +/- 5.05). Intracellular pH (pHi) was, however, significantly increased in hypoxic active TSM to 7.71 +/- 0.05 as compared to 7.30 +/- 0.03 in normoxic active muscle. pHi of resting normoxic muscle (7.20 +/- 0.04) was statistically not different from that of resting hypoxic muscle. The pHi's of resting normoxic and active hypoxic muscles were significantly different. These results show that under in vitro, hypoxic conditions: 1) an increase in glycolysis in TSM is indicated by the increased lactate production, 2) there is a surprising, concomitant rise in pHi rather than a decrease as previously expected, and 3) it is mechanical activity of the muscle which leads to this paradoxical result, inasmuch as pHi is unaltered in the resting hypoxic muscle.", "contents": "Intracellular pH in hypoxic smooth muscle. Hypoxia impairs contractility in canine tracheal smooth muscle (TSM). This is attributed to intracellular lactacidosis. The present studies were undertaken to confirm this. Lactate was found to be significantly increased in hypoxic TSM (65.36 +/- 7.37 mg/100 g wet tissue), compared to normoxic (29.83 +/- 5.05). Intracellular pH (pHi) was, however, significantly increased in hypoxic active TSM to 7.71 +/- 0.05 as compared to 7.30 +/- 0.03 in normoxic active muscle. pHi of resting normoxic muscle (7.20 +/- 0.04) was statistically not different from that of resting hypoxic muscle. The pHi's of resting normoxic and active hypoxic muscles were significantly different. These results show that under in vitro, hypoxic conditions: 1) an increase in glycolysis in TSM is indicated by the increased lactate production, 2) there is a surprising, concomitant rise in pHi rather than a decrease as previously expected, and 3) it is mechanical activity of the muscle which leads to this paradoxical result, inasmuch as pHi is unaltered in the resting hypoxic muscle."}
{"id": "PMID:14514", "title": "Neuroleptic drug levels and therapeutic response: preliminary observations with red blood cell bound butaperazine.", "content": "The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a \"therapeutic window\", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients.", "contents": "Neuroleptic drug levels and therapeutic response: preliminary observations with red blood cell bound butaperazine. The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a \"therapeutic window\", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients."}
{"id": "PMID:14516", "title": "Systemic artery--pulmonary artery communication in Takayasu's arteritis.", "content": "Four cases of Takayasu's arteritis in which systemic artery-pulmonary artery communication is demonstrated on thoracic aortography are presented. Pulmonary arterial involvement in Takayasu's arteritis seems to be more frequent than generally appreciated (12% in the present series). Demonstration of the communication in the absence of evidence of other causes of a shunt is strongly suggestive of pulmonary artery involvement. It is not necessary to perform pulmonary angiography to confirm the involvement unless clinically indicated. It is also stressed that the presence of pulmonary artery involvement is useful to differentiate Takayasy's arteritis from arteriosclerosis.", "contents": "Systemic artery--pulmonary artery communication in Takayasu's arteritis. Four cases of Takayasu's arteritis in which systemic artery-pulmonary artery communication is demonstrated on thoracic aortography are presented. Pulmonary arterial involvement in Takayasu's arteritis seems to be more frequent than generally appreciated (12% in the present series). Demonstration of the communication in the absence of evidence of other causes of a shunt is strongly suggestive of pulmonary artery involvement. It is not necessary to perform pulmonary angiography to confirm the involvement unless clinically indicated. It is also stressed that the presence of pulmonary artery involvement is useful to differentiate Takayasy's arteritis from arteriosclerosis."}
{"id": "PMID:14518", "title": "[Effect of run-training and run-stress on glucose assimilation and insulin release in rats of different age (author's transl)].", "content": "82 male rats of different age have been investigated after a definitive run-training, after a run-training with subsequent run-stress and after a run-stress without run-training. An intravenous glucose tolerance test has been done measuring glucose and insulin serum levels before and after i.v. glucose application. Data obtained in this study demonstrate that: 1. adult rats have a better glucose assimilation and higher insulin serum levels after i.v. glucose than older ones. 2. run-stress leads to a deterioration of glucose assimilation and diminution of insulin release in rats of any age. 3. run-training improves glucose tolerance and saves insulin at the same time. 4. in old rats, which have never done any training before, run-training improves glucose assimilation, too. 5. run-stress after run-training has a different effect on adult and old rats: In adult rats there is nearly no effect on glucose assimilation and insulin release in comparison to control animals, while old rats show a significant deterioration of glucose assimilation in comparison to control rats of the same age. Obviously the effect of run-training is less distinct in old rats despite of similar running work.", "contents": "[Effect of run-training and run-stress on glucose assimilation and insulin release in rats of different age (author's transl)]. 82 male rats of different age have been investigated after a definitive run-training, after a run-training with subsequent run-stress and after a run-stress without run-training. An intravenous glucose tolerance test has been done measuring glucose and insulin serum levels before and after i.v. glucose application. Data obtained in this study demonstrate that: 1. adult rats have a better glucose assimilation and higher insulin serum levels after i.v. glucose than older ones. 2. run-stress leads to a deterioration of glucose assimilation and diminution of insulin release in rats of any age. 3. run-training improves glucose tolerance and saves insulin at the same time. 4. in old rats, which have never done any training before, run-training improves glucose assimilation, too. 5. run-stress after run-training has a different effect on adult and old rats: In adult rats there is nearly no effect on glucose assimilation and insulin release in comparison to control animals, while old rats show a significant deterioration of glucose assimilation in comparison to control rats of the same age. Obviously the effect of run-training is less distinct in old rats despite of similar running work."}
{"id": "PMID:14519", "title": "[Investigations on LH and FSH serum levels before and after application of synthetic LH-releasing-hormone in healthy men of different age].", "content": "50 male healthy volunteers of different age had measurements of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Basal levels of LH and FSH as well as maximal release of both hormones after i.v. application of 25 mug of synthetical LH-releasing hormone have been done. Results demonstrate an increasing reserve capacity of LH and FSH with age. FSH/LH ratio is altered in favor of FSH with duration of life. Sensitivity of gonadotropin producing cells of adenohypophysis to LH-releasing hormone is diminished in old age that can be recognized from a diminution of the relative rise of serum LH and FSH after LH-RH application. Correlations and partial correlations of absolute and relative body weight with age and basal LH and FSH serum levels demonstrate that age and not body weight plays a main part for increasing gonadotropin serum values. Causative responsibility for the increased LH serum concentrations is a decrease of testosterone production with age. Data obtained in this study and reports presented in literature give no convincing explanation for the increase of FSH serum levels with age.", "contents": "[Investigations on LH and FSH serum levels before and after application of synthetic LH-releasing-hormone in healthy men of different age]. 50 male healthy volunteers of different age had measurements of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Basal levels of LH and FSH as well as maximal release of both hormones after i.v. application of 25 mug of synthetical LH-releasing hormone have been done. Results demonstrate an increasing reserve capacity of LH and FSH with age. FSH/LH ratio is altered in favor of FSH with duration of life. Sensitivity of gonadotropin producing cells of adenohypophysis to LH-releasing hormone is diminished in old age that can be recognized from a diminution of the relative rise of serum LH and FSH after LH-RH application. Correlations and partial correlations of absolute and relative body weight with age and basal LH and FSH serum levels demonstrate that age and not body weight plays a main part for increasing gonadotropin serum values. Causative responsibility for the increased LH serum concentrations is a decrease of testosterone production with age. Data obtained in this study and reports presented in literature give no convincing explanation for the increase of FSH serum levels with age."}
{"id": "PMID:14520", "title": "[Sexual hormones in ageing males (author's transl)].", "content": "Alterations of sexual hormones in plasma of ageing males occur between the 50th and 60th year of life with individual variations: 1. Decreased values of testosterone in plasma and a poor response to gonadotrophins demonstrate a diminished synthesizing capacity of the testes in old men. 2. The decreased testosterone plasma values are followed by an increase in LH. The response of the anterior pituitary gland to LH-RH stimulation in old men is normal. 3. Under basal conditions estrone as well as estradiol plasma concentrations increase significantly with age because of increased conversion from androgens. 4. Parallel to estrogen plasma values an increased concentration of the sexual hormone binding globulin (SHBG) is found, resulting in a steep decrease of the free (= active) testosterone fraction. 5. Decreased testosterone, which is more strongly bound to SHBG and increased estrone and estradiol plasma values result in an androgen/estrogen imbalance in old men.", "contents": "[Sexual hormones in ageing males (author's transl)]. Alterations of sexual hormones in plasma of ageing males occur between the 50th and 60th year of life with individual variations: 1. Decreased values of testosterone in plasma and a poor response to gonadotrophins demonstrate a diminished synthesizing capacity of the testes in old men. 2. The decreased testosterone plasma values are followed by an increase in LH. The response of the anterior pituitary gland to LH-RH stimulation in old men is normal. 3. Under basal conditions estrone as well as estradiol plasma concentrations increase significantly with age because of increased conversion from androgens. 4. Parallel to estrogen plasma values an increased concentration of the sexual hormone binding globulin (SHBG) is found, resulting in a steep decrease of the free (= active) testosterone fraction. 5. Decreased testosterone, which is more strongly bound to SHBG and increased estrone and estradiol plasma values result in an androgen/estrogen imbalance in old men."}
{"id": "PMID:14521", "title": "[Geriatric change of thyroid function and thyroid diseases (author's transl)].", "content": "The geriatric changes of thyroid function in healthy individuals are relatively low; therefore it is not necessary to take it into consideration for routine diagnostic work. Thyroid diseases show an increase with age and also a change of the clinical picture. Therefore, and because of being superimposed by symptoms of simulatneous second disease, it is necessary to start with the specific diagnostic earlier than in younger patients.", "contents": "[Geriatric change of thyroid function and thyroid diseases (author's transl)]. The geriatric changes of thyroid function in healthy individuals are relatively low; therefore it is not necessary to take it into consideration for routine diagnostic work. Thyroid diseases show an increase with age and also a change of the clinical picture. Therefore, and because of being superimposed by symptoms of simulatneous second disease, it is necessary to start with the specific diagnostic earlier than in younger patients."}
{"id": "PMID:14522", "title": "Functional changes of the aging rat retina in relation to the modifications of the ERG components.", "content": "the intact eye of Wistar rat was stimulated with continual periodic light signals in the range of 0,001-500 lux and from 0,01 cps. up to the fusionfrequency. Using square-wave light stimuli of the frequency range from 0,01 to 0,1 cps. and intensity diapason of 0,1-1,0 lux the scotopic electroretinogram (ERG) consists of the following waves: b, b-negative, c, d, d-positive, respectively. At the beginning of the light sensitivity range, that is near above the threshold, on one part and over a stimulus intensity of 10 lux, on the other the ERG becomes more simple and looks appr. like a direct current (DC) response. Along with aging the ERG undergoes changing. The light sensitivity of the eye proved to be decreased, especially in the short wave range of the spectrum. Thus the ERG threshold becomes increased. The DC components are less apparent. The fast elements of high amplitudes are also missing. The slope of the frontal and descending part of the wave b gets lower. The fusion-frequency is lower with old animals as well. The spontaneous physiological biopotential noise level is significantly higher and the synchronity of elements participating in generating the ERG wave is less. Additionally a considerable great slowing-down of the adaptation processes were observed. Using light signals of different wave forms, it may be established, that differentiating ability of the retina declines more rapidly as aging advances than that of its light sensitivity.", "contents": "Functional changes of the aging rat retina in relation to the modifications of the ERG components. the intact eye of Wistar rat was stimulated with continual periodic light signals in the range of 0,001-500 lux and from 0,01 cps. up to the fusionfrequency. Using square-wave light stimuli of the frequency range from 0,01 to 0,1 cps. and intensity diapason of 0,1-1,0 lux the scotopic electroretinogram (ERG) consists of the following waves: b, b-negative, c, d, d-positive, respectively. At the beginning of the light sensitivity range, that is near above the threshold, on one part and over a stimulus intensity of 10 lux, on the other the ERG becomes more simple and looks appr. like a direct current (DC) response. Along with aging the ERG undergoes changing. The light sensitivity of the eye proved to be decreased, especially in the short wave range of the spectrum. Thus the ERG threshold becomes increased. The DC components are less apparent. The fast elements of high amplitudes are also missing. The slope of the frontal and descending part of the wave b gets lower. The fusion-frequency is lower with old animals as well. The spontaneous physiological biopotential noise level is significantly higher and the synchronity of elements participating in generating the ERG wave is less. Additionally a considerable great slowing-down of the adaptation processes were observed. Using light signals of different wave forms, it may be established, that differentiating ability of the retina declines more rapidly as aging advances than that of its light sensitivity."}
{"id": "PMID:14523", "title": "[Assessment of the biological age in the animal-experiment (author's transl)].", "content": "Experimental investigations of internal and external factors presumably influencing the aging process require an objective assessment of the biological age or vitality respectively by means of as many age parameters as possible. Using the rat, a valuable test animal in experimental gerontology, whose life expectancy of about 40 month allows longitudinal studies, a standard test programm for the estimation of the biological age has been developed. The age parameters used originate from investigations of 1. the tail tendon collagen, 2. the skin, 3. the aorta, 4. the ECG, 5. the lipofuscin content of brain and heart, 6. the tissue respiration of various organs, 7, the motor activity and 8. learning and memory. Using the above-mentioned age parameters a statistical measure for the biological age will be calculated by means of multivariate analysis and will allow the comparison of differeent age-and experimental-groups.", "contents": "[Assessment of the biological age in the animal-experiment (author's transl)]. Experimental investigations of internal and external factors presumably influencing the aging process require an objective assessment of the biological age or vitality respectively by means of as many age parameters as possible. Using the rat, a valuable test animal in experimental gerontology, whose life expectancy of about 40 month allows longitudinal studies, a standard test programm for the estimation of the biological age has been developed. The age parameters used originate from investigations of 1. the tail tendon collagen, 2. the skin, 3. the aorta, 4. the ECG, 5. the lipofuscin content of brain and heart, 6. the tissue respiration of various organs, 7, the motor activity and 8. learning and memory. Using the above-mentioned age parameters a statistical measure for the biological age will be calculated by means of multivariate analysis and will allow the comparison of differeent age-and experimental-groups."}
{"id": "PMID:14524", "title": "[Investigation of memory in experimental gerontology (author's transl)].", "content": "The possible transfer of learning performance by proteins and ribonucleic acids was studied. 140 male Sprague-Dawley rats aged 3 months and 68 aged 20 months were used. Proteins and ribonucleic acids were isolated from the brains of trained and untrained rats aged 3 months. The difference in learning performance was tested and the incorporation of the above-mentioned substances into the hippo-campus and the residual brain in the two age-groups was measured using radioactive labelled material. A specific transfer of learned information-contents on the molecular level was found only after transfer of proteins in both young and old rats; the results of the training are well correlated with those of the incorporation. The two age-groups differ especially with regard to the learning performance, expressed in the error number. In th older group the error number is significantly lower in contrast to the learning time, that is slightly shorter in the younger group. This can be explained by the differences between the incorporation of brain proteins of trained animals into animals of different age, as well as by the investigations of some authors, who distinguished between different modes of learning. The lower incorporation of labelled substance into the brains of old animals is remarkable; the conclusion is a lower turnover of these substances in the brain of old animals, especially of the ribonucleic-acids. Nevertheless the learning performance of complex information-contents is not impaired.", "contents": "[Investigation of memory in experimental gerontology (author's transl)]. The possible transfer of learning performance by proteins and ribonucleic acids was studied. 140 male Sprague-Dawley rats aged 3 months and 68 aged 20 months were used. Proteins and ribonucleic acids were isolated from the brains of trained and untrained rats aged 3 months. The difference in learning performance was tested and the incorporation of the above-mentioned substances into the hippo-campus and the residual brain in the two age-groups was measured using radioactive labelled material. A specific transfer of learned information-contents on the molecular level was found only after transfer of proteins in both young and old rats; the results of the training are well correlated with those of the incorporation. The two age-groups differ especially with regard to the learning performance, expressed in the error number. In th older group the error number is significantly lower in contrast to the learning time, that is slightly shorter in the younger group. This can be explained by the differences between the incorporation of brain proteins of trained animals into animals of different age, as well as by the investigations of some authors, who distinguished between different modes of learning. The lower incorporation of labelled substance into the brains of old animals is remarkable; the conclusion is a lower turnover of these substances in the brain of old animals, especially of the ribonucleic-acids. Nevertheless the learning performance of complex information-contents is not impaired."}
{"id": "PMID:14525", "title": "[Paranoid syndromes in the involution (author's transl)].", "content": "Conditions of outbreak and chronification of paranoid syndromes, including the existence of an \"axial syndrome\" and behaviour theories are hypothetically summarized. The individual characteristics of patients with the first paranoid symptoms during involution appear to depend mainly on three factors: the theme of the delusion seems to be connected with the age at the onset, in more than half of the male patients exogenous psychoorganic symptoms were observed, and in females however predominantly manic-depressive syndroms could be found.", "contents": "[Paranoid syndromes in the involution (author's transl)]. Conditions of outbreak and chronification of paranoid syndromes, including the existence of an \"axial syndrome\" and behaviour theories are hypothetically summarized. The individual characteristics of patients with the first paranoid symptoms during involution appear to depend mainly on three factors: the theme of the delusion seems to be connected with the age at the onset, in more than half of the male patients exogenous psychoorganic symptoms were observed, and in females however predominantly manic-depressive syndroms could be found."}
{"id": "PMID:14526", "title": "[Genetic aspects of aging (author's transl)].", "content": "The experimental results indicating a primary genetic cause of aging and some diseases of the old age (cancer, arteriosclerosis, immune deficiency, autoimmune diseases) are summarized under two aspects: 1) The genetic influence is determined during the differentiation and development phase of the organism, whereby the direct or indirect (pleiotropic effect) selection of genes of aging, or the missing selection of genes which are acting against aging come into consideration. 2) The dicisive gene alterations take place by spontaneous and/or induced somatic mutations.", "contents": "[Genetic aspects of aging (author's transl)]. The experimental results indicating a primary genetic cause of aging and some diseases of the old age (cancer, arteriosclerosis, immune deficiency, autoimmune diseases) are summarized under two aspects: 1) The genetic influence is determined during the differentiation and development phase of the organism, whereby the direct or indirect (pleiotropic effect) selection of genes of aging, or the missing selection of genes which are acting against aging come into consideration. 2) The dicisive gene alterations take place by spontaneous and/or induced somatic mutations."}
{"id": "PMID:14527", "title": "[Study of age and sex dependance in renal clearances with radioisotopes (author's transl)].", "content": "In 85 patients between 15 and 95 years of age (40 male patients and 45 females) without any signs of renal disease (concentration of serum creatinine below 1,4 mg/100ml, normal diastolic blood pressure and normal urine analysis) a highly significant negative correlation was found between glomerular filtration rate (GFR, determined by 51Cr-EDTA - slope-clearance) and renal plasma flow (RPF, determined by 131J-oJHS-iodinehippuricacid-totalclearance) on one side and age on the other. Beginning with a basic value of 160 ml in males and 144 ml in females for GFR, the average decrease per year was 1,2 ml/1,0 ml respectively. The basis value of RPF was 854 ml for males and 673 ml for females, the decrease per year was 5,4 ml in men and 2,9 ml in women. The importance of physiological diminution of clearance values in elderly patients and its consequences for therapy are discussed. The more exact and methodically simpler 51Cr-EDTA-slope-clearance without urine collection should be used instead of the somewhat inaccurate determination of endogenous creatinine clearance especially in older patients.", "contents": "[Study of age and sex dependance in renal clearances with radioisotopes (author's transl)]. In 85 patients between 15 and 95 years of age (40 male patients and 45 females) without any signs of renal disease (concentration of serum creatinine below 1,4 mg/100ml, normal diastolic blood pressure and normal urine analysis) a highly significant negative correlation was found between glomerular filtration rate (GFR, determined by 51Cr-EDTA - slope-clearance) and renal plasma flow (RPF, determined by 131J-oJHS-iodinehippuricacid-totalclearance) on one side and age on the other. Beginning with a basic value of 160 ml in males and 144 ml in females for GFR, the average decrease per year was 1,2 ml/1,0 ml respectively. The basis value of RPF was 854 ml for males and 673 ml for females, the decrease per year was 5,4 ml in men and 2,9 ml in women. The importance of physiological diminution of clearance values in elderly patients and its consequences for therapy are discussed. The more exact and methodically simpler 51Cr-EDTA-slope-clearance without urine collection should be used instead of the somewhat inaccurate determination of endogenous creatinine clearance especially in older patients."}
{"id": "PMID:14528", "title": "[The significance of experimental gerontology for clinical geriatrics (author's transl)].", "content": "Aging is a physiological process. The experimental gerontology is substantially a purely theoretical science. In the future, however, it will attain increasingly more significance for many fields of medicine. After presenting a survey covering the most important theories of aging it is shortly entered into the efforts to establish a mathematical model of multicellular aging (Beier, Brehme and Wiegel 1973). Furthermore an introduction is given into a longitudinal program (3 years) of the own experimental-gerontological research using about 1000 Sprague-Dawley rats and age parameters. The mathematical evaluation of the results shall contribute to come to more exact and objective statements  about age and vitality. The significance of the theoretical-experimental gerontology lies mainly in its efforts to study the fundamental conditions and the possibilities for a longer maintenance of vitality by systematic measures and to reduce or retard the susceptibility to the socalled age-diseases.", "contents": "[The significance of experimental gerontology for clinical geriatrics (author's transl)]. Aging is a physiological process. The experimental gerontology is substantially a purely theoretical science. In the future, however, it will attain increasingly more significance for many fields of medicine. After presenting a survey covering the most important theories of aging it is shortly entered into the efforts to establish a mathematical model of multicellular aging (Beier, Brehme and Wiegel 1973). Furthermore an introduction is given into a longitudinal program (3 years) of the own experimental-gerontological research using about 1000 Sprague-Dawley rats and age parameters. The mathematical evaluation of the results shall contribute to come to more exact and objective statements  about age and vitality. The significance of the theoretical-experimental gerontology lies mainly in its efforts to study the fundamental conditions and the possibilities for a longer maintenance of vitality by systematic measures and to reduce or retard the susceptibility to the socalled age-diseases."}
{"id": "PMID:14530", "title": "[A serogenetic approach to the study of Alzheimer's disease (author's transl)].", "content": "The analysis of 15 hereditary controlled blood characteristics in 57 Alzheimer-patients revealed abnormalities in the distribution of ABO-blood-groups and phenotypes in the third component of complement system. These data indicate that the phenogenesis of the Alzheimer syndrome is multiconditional and is obviously influenced by selective processes of immuno-genetic factors. This selective vulnerability offers a lead into the elucidation of amyloid deposition in Alzheimer's disease.", "contents": "[A serogenetic approach to the study of Alzheimer's disease (author's transl)]. The analysis of 15 hereditary controlled blood characteristics in 57 Alzheimer-patients revealed abnormalities in the distribution of ABO-blood-groups and phenotypes in the third component of complement system. These data indicate that the phenogenesis of the Alzheimer syndrome is multiconditional and is obviously influenced by selective processes of immuno-genetic factors. This selective vulnerability offers a lead into the elucidation of amyloid deposition in Alzheimer's disease."}
{"id": "PMID:14531", "title": "[The effect of prednisolone on the development of the galactosamine hepatitis of young and old rats (author's transl)].", "content": "The present work reports on kinetic and morphological studies of one hundred female albino rats after the administration of galactosamine and galactosamine and prednisolone. The results demonstrate a significant higher increase of the serum transaminasess got and gpt in the older than in the younger rats as well as a protecting effect of prenisolone against galactosamine produced disturbances. In the thirty months old rats the protection against morphological and biochemical disturbances was only demonstrable for the first twelve hours after the administration of galactosamine.", "contents": "[The effect of prednisolone on the development of the galactosamine hepatitis of young and old rats (author's transl)]. The present work reports on kinetic and morphological studies of one hundred female albino rats after the administration of galactosamine and galactosamine and prednisolone. The results demonstrate a significant higher increase of the serum transaminasess got and gpt in the older than in the younger rats as well as a protecting effect of prenisolone against galactosamine produced disturbances. In the thirty months old rats the protection against morphological and biochemical disturbances was only demonstrable for the first twelve hours after the administration of galactosamine."}
{"id": "PMID:14532", "title": "[Age-dependent changes of hypophysis-thyroid - regulation (author's transl)].", "content": "In health men and women different age total thyroxine, free thyroxine-binding-capacity, total triiodothyronine as well as TSH in serum before and after intravenous application of 500 mcg synthetic thyrothropine-releasing-hormone (TRH) were controlled. The investigations have shown: 1. With increasing age total thyroxine level in serum does not change. 2. With increasing age free thyroxine-binding-capacity in serum does not change. 3. With increasing age in men and women a significant decrease of total triiodothyronine in serum is to be measured. 4. Basal TSH serum levels do not change with increasing age. On the other hand in men and women with increasing age significant decreased TSH increments after TRH application were measured. The investigations have shown, that with increasing age the hypothalamus-hypophysial-thyroid-axis is shifting to a lower regulation level.", "contents": "[Age-dependent changes of hypophysis-thyroid - regulation (author's transl)]. In health men and women different age total thyroxine, free thyroxine-binding-capacity, total triiodothyronine as well as TSH in serum before and after intravenous application of 500 mcg synthetic thyrothropine-releasing-hormone (TRH) were controlled. The investigations have shown: 1. With increasing age total thyroxine level in serum does not change. 2. With increasing age free thyroxine-binding-capacity in serum does not change. 3. With increasing age in men and women a significant decrease of total triiodothyronine in serum is to be measured. 4. Basal TSH serum levels do not change with increasing age. On the other hand in men and women with increasing age significant decreased TSH increments after TRH application were measured. The investigations have shown, that with increasing age the hypothalamus-hypophysial-thyroid-axis is shifting to a lower regulation level."}
{"id": "PMID:14533", "title": "[Problemss of tending to chronicity of diseases in geriatrics (author's transl)].", "content": "The most important alterations of the old age are mentioned. They have a great influence on the behaviour of the elderly in a hospital. Charactersitic behaviour patterns at admission, during hospitalization and at dismission are pointed out. Multimorbidity should not cause a thoughtless and highly technical work-up. Rehabilitation measures in order to keep the patient in bed as short as possible are important. For this reason the nursing staff should have a good knowledge of activating care. Pharmacogherapy, intensive care, preoperative and postoperative care are mentioned.", "contents": "[Problemss of tending to chronicity of diseases in geriatrics (author's transl)]. The most important alterations of the old age are mentioned. They have a great influence on the behaviour of the elderly in a hospital. Charactersitic behaviour patterns at admission, during hospitalization and at dismission are pointed out. Multimorbidity should not cause a thoughtless and highly technical work-up. Rehabilitation measures in order to keep the patient in bed as short as possible are important. For this reason the nursing staff should have a good knowledge of activating care. Pharmacogherapy, intensive care, preoperative and postoperative care are mentioned."}
{"id": "PMID:14534", "title": "[Medical treatment and rehabilitation measures for the elderly--discussion of the financial problems involved (author's transl)].", "content": "The National Pension Insurance and Health Insurance Schemes up to now share the expenses of health insurance for the elderly. The shares to be carried by each body are again and again subject to political discussion. Since nursing home care is up to now not accepted as being an integral part of health care, the social welfare system is forced to cover the expenses involved to a continuously increasing degree. While it can be shown, that health insurance for the elderly has greatly improved since its introduction in 1941, there nevertheless remain elements of discrimination of those no longer belonging to the age group with access to gainful employment. Discussing different measures of solution in the context of existing insurance systems, the National Pension Insurance would seem to be the body best suited to take over the whole responsibility of financing health insurance measures for the elderly. Another alternative would be to let the pensioneers themselves come up for the costs of their health insurance, or the decision may be taken to establish a new insurance system directed at covering the risks of long term illness for all age groups.", "contents": "[Medical treatment and rehabilitation measures for the elderly--discussion of the financial problems involved (author's transl)]. The National Pension Insurance and Health Insurance Schemes up to now share the expenses of health insurance for the elderly. The shares to be carried by each body are again and again subject to political discussion. Since nursing home care is up to now not accepted as being an integral part of health care, the social welfare system is forced to cover the expenses involved to a continuously increasing degree. While it can be shown, that health insurance for the elderly has greatly improved since its introduction in 1941, there nevertheless remain elements of discrimination of those no longer belonging to the age group with access to gainful employment. Discussing different measures of solution in the context of existing insurance systems, the National Pension Insurance would seem to be the body best suited to take over the whole responsibility of financing health insurance measures for the elderly. Another alternative would be to let the pensioneers themselves come up for the costs of their health insurance, or the decision may be taken to establish a new insurance system directed at covering the risks of long term illness for all age groups."}
{"id": "PMID:14535", "title": "[Clinical use of a thermal method for measuring peripheral blood flow according to A.M. Baptista (author's transl)].", "content": "Measurement of peripheral circulation according to Baptista is discussed and its applicability in clinical work demonstrated. Examples are given showing changes following peroral treatment with inositol niacinate and intra-arterial injection of carbon dioxide.", "contents": "[Clinical use of a thermal method for measuring peripheral blood flow according to A.M. Baptista (author's transl)]. Measurement of peripheral circulation according to Baptista is discussed and its applicability in clinical work demonstrated. Examples are given showing changes following peroral treatment with inositol niacinate and intra-arterial injection of carbon dioxide."}
{"id": "PMID:14536", "title": "[Peculiarities of unconditioned and conditioned reflex stimuli effects on secretory function of gastric glands in elderly and senile people (author's transl)].", "content": "For understanding age peculiarities of gastric secretory function in aging.tory function in aging.tory function regulation, the investigation of nervous influences on gastric secretion is of importance. With this end in view the unconditioned reflex stimulus- the tube with rubber balloon, containing 10 ml of water and conditioned reflex stimulus - food stimulus were employed. The fractional gastric intubation was carried out. The gastric secretion in response to mechanical stimulus was investigated in 125 persons aged 60-89 and in 40 persons aged 20-25 (control group). In response to conditioned reflex stimulus it was studied in 30 persons aged 60-89 and 10 persons aged 20-35 (control group). With aging the response of gastric glands to unconditioned and conditioned stimuli was found to decrease. The amount of secretion, hydrochloric acid, pepsin, and gastromuco-protein were decreased, the secretory effect being more slowly developed, the torpid secretion type being observed. The above facts testify to changes of nervous regulation of gastric secre", "contents": "[Peculiarities of unconditioned and conditioned reflex stimuli effects on secretory function of gastric glands in elderly and senile people (author's transl)]. For understanding age peculiarities of gastric secretory function in aging.tory function in aging.tory function regulation, the investigation of nervous influences on gastric secretion is of importance. With this end in view the unconditioned reflex stimulus- the tube with rubber balloon, containing 10 ml of water and conditioned reflex stimulus - food stimulus were employed. The fractional gastric intubation was carried out. The gastric secretion in response to mechanical stimulus was investigated in 125 persons aged 60-89 and in 40 persons aged 20-25 (control group). In response to conditioned reflex stimulus it was studied in 30 persons aged 60-89 and 10 persons aged 20-35 (control group). With aging the response of gastric glands to unconditioned and conditioned stimuli was found to decrease. The amount of secretion, hydrochloric acid, pepsin, and gastromuco-protein were decreased, the secretory effect being more slowly developed, the torpid secretion type being observed. The above facts testify to changes of nervous regulation of gastric secre"}
{"id": "PMID:14537", "title": "[Incorporation of 14-C-Glycine during galactosamine hepatitis of young and old rats (author's transl)a*].", "content": "The present work reports on incorporation of 14-Cglycine in the proteins of three liver fractions after the application of D-Galactosamine and D-Galactosamine + Prednisolone. 164 females albino rats were used in the experiments. The results demonstrate a higher rate of glycine incorporation in thirty months than in six weeks old animals. There is also a different age depending effect of prednisolone. The results are discussed in the light of reports from the literature.ports from the literature.", "contents": "[Incorporation of 14-C-Glycine during galactosamine hepatitis of young and old rats (author's transl)a*]. The present work reports on incorporation of 14-Cglycine in the proteins of three liver fractions after the application of D-Galactosamine and D-Galactosamine + Prednisolone. 164 females albino rats were used in the experiments. The results demonstrate a higher rate of glycine incorporation in thirty months than in six weeks old animals. There is also a different age depending effect of prednisolone. The results are discussed in the light of reports from the literature.ports from the literature."}
{"id": "PMID:14538", "title": "[The correlations between aging and drug effects (author's transl)].", "content": "Four examples (Methamphetamine, Testosterone, Caffeine, Cysteamine) have demonstrated that the response of the organism to a drug is primarily dependent upon the functional status of the organ concerned. If this functional status changes with age, then accordingly the reaction to the drug also changes. If, however, one alters the functional status of an organ in the elderly organism, e.g. inducing increased production of DNA in the liver by partial hepatectomy, the reaction of the organ now follows a pattern comparable to the juvenile organism, rather than being dependent on chronological age.", "contents": "[The correlations between aging and drug effects (author's transl)]. Four examples (Methamphetamine, Testosterone, Caffeine, Cysteamine) have demonstrated that the response of the organism to a drug is primarily dependent upon the functional status of the organ concerned. If this functional status changes with age, then accordingly the reaction to the drug also changes. If, however, one alters the functional status of an organ in the elderly organism, e.g. inducing increased production of DNA in the liver by partial hepatectomy, the reaction of the organ now follows a pattern comparable to the juvenile organism, rather than being dependent on chronological age."}
{"id": "PMID:14539", "title": "[Transitional phases in human development (author's transl)].", "content": "Transitional phases in the course of Human Development which divide the course of development into different steps, have been searched far from the old. These transitional phases are very often seen to be at least initiated by physical resp. biological changes and accompanied by psychological or mental changes. The results of the Life-span-Psychology and especially the findings of the biographical studies of our Psychological Institue, which were started in the Fifties, shows that there are Transitional phases which neither related to biological change nor to role change nor to the change from the one decade of life to the other one. Much more important are very personal experiences which very often lead to a reorientation. - These findings are in agreement with cognitive theory of personality, according to which human behavior is dependent more on the situation as perceived, than on the stimulus-pattern contigent with this situation. Therefore the study of these situational concepts of individual is relevant for the Life-span-Psychology and specially for the analysis of transitional phases.", "contents": "[Transitional phases in human development (author's transl)]. Transitional phases in the course of Human Development which divide the course of development into different steps, have been searched far from the old. These transitional phases are very often seen to be at least initiated by physical resp. biological changes and accompanied by psychological or mental changes. The results of the Life-span-Psychology and especially the findings of the biographical studies of our Psychological Institue, which were started in the Fifties, shows that there are Transitional phases which neither related to biological change nor to role change nor to the change from the one decade of life to the other one. Much more important are very personal experiences which very often lead to a reorientation. - These findings are in agreement with cognitive theory of personality, according to which human behavior is dependent more on the situation as perceived, than on the stimulus-pattern contigent with this situation. Therefore the study of these situational concepts of individual is relevant for the Life-span-Psychology and specially for the analysis of transitional phases."}
{"id": "PMID:14540", "title": "[Biological oriented research in gerontopsychiatrie (author's transl)].", "content": "Possible biological oriented research in geronto-psychiatry is discussed in relation to dementias. The discrimination between the various forms as well as against normal aging is dealt with. Reference is given to results of studies correlating clinical, neuropathological and neurophysiological date.", "contents": "[Biological oriented research in gerontopsychiatrie (author's transl)]. Possible biological oriented research in geronto-psychiatry is discussed in relation to dementias. The discrimination between the various forms as well as against normal aging is dealt with. Reference is given to results of studies correlating clinical, neuropathological and neurophysiological date."}
{"id": "PMID:14541", "title": "[Multidimensional pharmacopsychiatry in gerontopsychiatry: studies on the therapy with tricyclic antidepressant drugs (author's transl)].", "content": "A Concept for the multidimensional assessment and correlation of serum level and outcome of therapy with psychomopharmaca with chemical, psychological, psychophysiological, electroencephalographical and clinical methods is shown. It is possible by this method to correlate clinical outcome to serum level and effect of the drug and to objectivate the efficacy of the pharmacon. Applications in Gerontopsychiatry are discussed.", "contents": "[Multidimensional pharmacopsychiatry in gerontopsychiatry: studies on the therapy with tricyclic antidepressant drugs (author's transl)]. A Concept for the multidimensional assessment and correlation of serum level and outcome of therapy with psychomopharmaca with chemical, psychological, psychophysiological, electroencephalographical and clinical methods is shown. It is possible by this method to correlate clinical outcome to serum level and effect of the drug and to objectivate the efficacy of the pharmacon. Applications in Gerontopsychiatry are discussed."}
{"id": "PMID:14542", "title": "[Patients and their diseases in a geriatric hospital (author's transl)].", "content": "Report on patients and their problems of a hospital of chronic diseases. Geriatric departments, part of clinics of acute diseases should treat not only patients without real chance for rehabilitation or discharge. Most of the diseases of elder persons are such of the arterial system, especially of the cerebral and coronary vessels. Although patients suffered of partial or complete dementia and had to stay long in the hospital visitors came more often. Generally must be postulated, that all institutions for medical care or nursing of old people should cooperate better than today.", "contents": "[Patients and their diseases in a geriatric hospital (author's transl)]. Report on patients and their problems of a hospital of chronic diseases. Geriatric departments, part of clinics of acute diseases should treat not only patients without real chance for rehabilitation or discharge. Most of the diseases of elder persons are such of the arterial system, especially of the cerebral and coronary vessels. Although patients suffered of partial or complete dementia and had to stay long in the hospital visitors came more often. Generally must be postulated, that all institutions for medical care or nursing of old people should cooperate better than today."}
{"id": "PMID:14544", "title": "[Indications for orthopedic procedures in old people (author's transl)].", "content": "Advancements in general medicine and anesthesiology have enabled surgical procedures in old people with diminished risks. With reference to special problems the absolute indication for orthopedic procedures particularly for the old can be demonstrated.", "contents": "[Indications for orthopedic procedures in old people (author's transl)]. Advancements in general medicine and anesthesiology have enabled surgical procedures in old people with diminished risks. With reference to special problems the absolute indication for orthopedic procedures particularly for the old can be demonstrated."}
{"id": "PMID:14545", "title": "Model systems for studies on cellular basis of organ ageing.", "content": "The cellular basis of the age-related decline in the functional capacity of many mammalian organs is still poorly understood. In this paper, the rat liver is presented as a promising model for studying cellular phenomena underlying organ ageing. The recent development of methods for isolation and purification of parenchymal, Kupffer and endothelial cells from the rat liver makes possible the comparison of functional and metabolic changes in the intact liver with changes in distinct liver cell classes isolated from rats of various age groups. An attempt has been made to correlate age changes in some important liver-specific functions, such as bromsulophthalein uptake and albumin synthesis, at the organ and at the cellular level. To compare cellular ageing phenomena in long-lived cells (parenchymal cells) and short lived cells (Kupffer and endothelial cells) from the same organ, the role of lysosomes in cellular ageing processes was investigated, with secial reference to the functioning of the lysosomal enzyme cathepsin D. The specific cathepsin D activity in Kupffer cells was abour 3 times higher than in endothelial cells and about 20 times higher than in parenchymal cells. The enzyme activity in the latter cell type showed a significant increase with age.", "contents": "Model systems for studies on cellular basis of organ ageing. The cellular basis of the age-related decline in the functional capacity of many mammalian organs is still poorly understood. In this paper, the rat liver is presented as a promising model for studying cellular phenomena underlying organ ageing. The recent development of methods for isolation and purification of parenchymal, Kupffer and endothelial cells from the rat liver makes possible the comparison of functional and metabolic changes in the intact liver with changes in distinct liver cell classes isolated from rats of various age groups. An attempt has been made to correlate age changes in some important liver-specific functions, such as bromsulophthalein uptake and albumin synthesis, at the organ and at the cellular level. To compare cellular ageing phenomena in long-lived cells (parenchymal cells) and short lived cells (Kupffer and endothelial cells) from the same organ, the role of lysosomes in cellular ageing processes was investigated, with secial reference to the functioning of the lysosomal enzyme cathepsin D. The specific cathepsin D activity in Kupffer cells was abour 3 times higher than in endothelial cells and about 20 times higher than in parenchymal cells. The enzyme activity in the latter cell type showed a significant increase with age."}
{"id": "PMID:14546", "title": "Age-dependent increase of intranuclear monovalent electrolytes as revealed by quantitative energy dispersive x-ray microanalysis.", "content": "The concentration of univalent electrolytes in the cell nucleus and cytoplasm of the big neurons of the brain and in hepatocytes was established in young, mature and old rats by means of microanalysis with X-rays. It was demonstrated that the Na+ and Cl-- content increases with aging in both tissues, while K+ increases in the neurons but not in the nuclei of the hepatocytes, At the same time some ions in the cytoplasm increase, while others decrease or remain stable. If a possible loss of water during aging is taken into consideration the result is a considerable increase in ion concentration in the nucleus. This may be regarded as one of the principal reasons for the increased density which accompanies aging and possibly as one of the cause of the aging process.", "contents": "Age-dependent increase of intranuclear monovalent electrolytes as revealed by quantitative energy dispersive x-ray microanalysis. The concentration of univalent electrolytes in the cell nucleus and cytoplasm of the big neurons of the brain and in hepatocytes was established in young, mature and old rats by means of microanalysis with X-rays. It was demonstrated that the Na+ and Cl-- content increases with aging in both tissues, while K+ increases in the neurons but not in the nuclei of the hepatocytes, At the same time some ions in the cytoplasm increase, while others decrease or remain stable. If a possible loss of water during aging is taken into consideration the result is a considerable increase in ion concentration in the nucleus. This may be regarded as one of the principal reasons for the increased density which accompanies aging and possibly as one of the cause of the aging process."}
{"id": "PMID:14547", "title": "On the relationship between the perichromatin granules and cellular ageing as well as cell differentiation.", "content": "Current hypotheses ascribe the role of pre-RNA storage or transport structures to the perichromatin granules. Their numerical density is directly related to the transcription activity of the nucleus. The perichromatin granules (P.K.) can be demonstrated in ultrathin sections with the stain used by Bernhard (1969) for ribonucleo-proteins. We have established the numerical density per unit of area in nuclear cross-sections of cells in young rats (1-2 months), old rats (26-29 months) and in relation to various cell function types. Cell aging causes a reduction in the numerical density of perichomatin granules in the big neurons of the cerebral cortex, the cerebellar granulocytes, the hepatocytes and the parotid cells. No age-related changes were found in the myocardial cells and erythroblasts of the same maturity. However, at the end of maturation, the number of perichromatin granules both in young and old erythroblasts was nil. (1) There is a quantitative reduction of perichromatin granules primarily in postmitotic and relatively postmitotic cells; (2) cell types showing no age-related reduction in perichromatin granules maintain high synthetic activity throughout their life; (3) the results confirm that relationships exist between numerical density of the perichromatin granules and cell activity; (4) the big fluctuations in the numbers of perichromatin granules in various cell types are probably connected with cell function.", "contents": "On the relationship between the perichromatin granules and cellular ageing as well as cell differentiation. Current hypotheses ascribe the role of pre-RNA storage or transport structures to the perichromatin granules. Their numerical density is directly related to the transcription activity of the nucleus. The perichromatin granules (P.K.) can be demonstrated in ultrathin sections with the stain used by Bernhard (1969) for ribonucleo-proteins. We have established the numerical density per unit of area in nuclear cross-sections of cells in young rats (1-2 months), old rats (26-29 months) and in relation to various cell function types. Cell aging causes a reduction in the numerical density of perichomatin granules in the big neurons of the cerebral cortex, the cerebellar granulocytes, the hepatocytes and the parotid cells. No age-related changes were found in the myocardial cells and erythroblasts of the same maturity. However, at the end of maturation, the number of perichromatin granules both in young and old erythroblasts was nil. (1) There is a quantitative reduction of perichromatin granules primarily in postmitotic and relatively postmitotic cells; (2) cell types showing no age-related reduction in perichromatin granules maintain high synthetic activity throughout their life; (3) the results confirm that relationships exist between numerical density of the perichromatin granules and cell activity; (4) the big fluctuations in the numbers of perichromatin granules in various cell types are probably connected with cell function."}
{"id": "PMID:14548", "title": "On the reversibility of some cytological ageing parameters of rat brain cells by phytohemagglutinin.", "content": "It has been shown that the thermal stability of DNA in the brain cortical cells increases with the age. At the same time, the number of perichromatin granules being connected in some way to the messenger RNA synthesis and transport of the interphase nuclei, decreases in the same cells. In vivo treatment of the old animals by mitogens like phytohemagglutinin induced a reversal of both ageing phenomena: the thermal stability of DNA returned almost completely to that of the young animals, whereas the number of perichromatin granules rised again to the young level.", "contents": "On the reversibility of some cytological ageing parameters of rat brain cells by phytohemagglutinin. It has been shown that the thermal stability of DNA in the brain cortical cells increases with the age. At the same time, the number of perichromatin granules being connected in some way to the messenger RNA synthesis and transport of the interphase nuclei, decreases in the same cells. In vivo treatment of the old animals by mitogens like phytohemagglutinin induced a reversal of both ageing phenomena: the thermal stability of DNA returned almost completely to that of the young animals, whereas the number of perichromatin granules rised again to the young level."}
{"id": "PMID:14549", "title": "[Chromosomal investigations in two age groups of human females].", "content": "Chromosomal analysis was performed in cultured lymphocytes from 32 old (ages 76-85, abbr. A) and 31 young (ages 15-20, abbr. J) patients, who were representative for a great part of the \"normal\" female population of the same age. In regard to culture time (48 and 72 hours) each age group was divided into two halves; 1500 cells were examined in each of the resulting four sub-units (A 48, A 72; J 48, J 72). Whereas the frequency of \"spontaneous\" gaps showed no dependency from age or culture time, single chromatid breaks were predominantly observed in A 72 and dicentric chromosomes in A 48. The mean breakage rates in the two age groups (A 48 2,4% A 72 3,0%; J 48 1,3%, J 72 1,7%) differed significantly for both culture times (Chi2 -test: A 48/J 48 p less than 0,01; A 72/J 72 p approximately 0,01). After karyotyping and additional application of a trypsin-Giemsa-branding-technique large, acentric \"fragments,\" which could only be detected in metaphases of old females (A 48 1,0%, A 72 0,5%), proved to be X-chromosomes with premature centromere division and a high tendency to non-disjunction. These results are in agreement with those published by Fitzgerald (8).", "contents": "[Chromosomal investigations in two age groups of human females]. Chromosomal analysis was performed in cultured lymphocytes from 32 old (ages 76-85, abbr. A) and 31 young (ages 15-20, abbr. J) patients, who were representative for a great part of the \"normal\" female population of the same age. In regard to culture time (48 and 72 hours) each age group was divided into two halves; 1500 cells were examined in each of the resulting four sub-units (A 48, A 72; J 48, J 72). Whereas the frequency of \"spontaneous\" gaps showed no dependency from age or culture time, single chromatid breaks were predominantly observed in A 72 and dicentric chromosomes in A 48. The mean breakage rates in the two age groups (A 48 2,4% A 72 3,0%; J 48 1,3%, J 72 1,7%) differed significantly for both culture times (Chi2 -test: A 48/J 48 p less than 0,01; A 72/J 72 p approximately 0,01). After karyotyping and additional application of a trypsin-Giemsa-branding-technique large, acentric \"fragments,\" which could only be detected in metaphases of old females (A 48 1,0%, A 72 0,5%), proved to be X-chromosomes with premature centromere division and a high tendency to non-disjunction. These results are in agreement with those published by Fitzgerald (8)."}
{"id": "PMID:14550", "title": "Age changes of turnover rates and subfraction composition of rat liver and spleen histones.", "content": "Histones from tissues of young and old rats have been compared. Lysine-rich F1 histone was found to be the only one which is tissue specific and whose subfraction pattern changes in old cells. The comparison of turnover rates of different histones from liver and spleen, measured by the level of 3H-leucine incorporation and subsequent decay of its specific activity with time, showed that while the activity and turnover or arginine-rich histones F3 and F2a2 was reduced in old liver, ageing was associated with increased turnover of F1 histone. The results are discussed from the point of view of a special role of F1 histone in the condensation of chromatin and in the age-related inhibition of some cellular functions.", "contents": "Age changes of turnover rates and subfraction composition of rat liver and spleen histones. Histones from tissues of young and old rats have been compared. Lysine-rich F1 histone was found to be the only one which is tissue specific and whose subfraction pattern changes in old cells. The comparison of turnover rates of different histones from liver and spleen, measured by the level of 3H-leucine incorporation and subsequent decay of its specific activity with time, showed that while the activity and turnover or arginine-rich histones F3 and F2a2 was reduced in old liver, ageing was associated with increased turnover of F1 histone. The results are discussed from the point of view of a special role of F1 histone in the condensation of chromatin and in the age-related inhibition of some cellular functions."}
{"id": "PMID:14551", "title": "[On the biophysical interpretation of ageing-factors (author's transl)].", "content": "The ageing-factor is a measure for the rate of ageing. In the model of vitality the error rate mu corresponds to the ageing-factor. The ageing-factors of several physical functions can be determined from the ascent of decrease of these functions. The standardized ageing-factors of the considered physiological functions range from 0.001 to 0.017 year--1 and are smaller than the ageing-factor of the whole organism. The date of the occurrence of pathological manifestations as a result of ageing-conditioned decrease of functions can be estimated by means of the ageing-factors.", "contents": "[On the biophysical interpretation of ageing-factors (author's transl)]. The ageing-factor is a measure for the rate of ageing. In the model of vitality the error rate mu corresponds to the ageing-factor. The ageing-factors of several physical functions can be determined from the ascent of decrease of these functions. The standardized ageing-factors of the considered physiological functions range from 0.001 to 0.017 year--1 and are smaller than the ageing-factor of the whole organism. The date of the occurrence of pathological manifestations as a result of ageing-conditioned decrease of functions can be estimated by means of the ageing-factors."}
{"id": "PMID:14552", "title": "[Free amino-acids of the plasma in atherosclerotic patients (author's transl)].", "content": "18 free amino-acids have been valuated in a group of patients recovering from myocardial infarction dating more than one year back and in another group of healthy active athlets. In the group of the ill persons the mean values of the following amino-acids were significantly higher: Arginine, asparagine-acid, phenylalanine, valine, lysine, serine, threonine, leucine, proline and tyrosine. While in the group of the healthy persons the following amino - acids proved to have significantly higher values: alpha -- aminobutter-acid, glycine and cystine. No significant differences between the mean values of both groups were to be found of the following amino - acids: Alanine, methionine, ornithine, isoleucine and histidine. In the group of the patients correlations of the free amino acids to both serumlipids and blood -- glucose could be calculated with significant results in a certain number of amino-acids. The results may suppose that the changes in the metabolism of atherosclerotic patients do not only effect the lipids and carbohydrates, but as well the free amino-acids.", "contents": "[Free amino-acids of the plasma in atherosclerotic patients (author's transl)]. 18 free amino-acids have been valuated in a group of patients recovering from myocardial infarction dating more than one year back and in another group of healthy active athlets. In the group of the ill persons the mean values of the following amino-acids were significantly higher: Arginine, asparagine-acid, phenylalanine, valine, lysine, serine, threonine, leucine, proline and tyrosine. While in the group of the healthy persons the following amino - acids proved to have significantly higher values: alpha -- aminobutter-acid, glycine and cystine. No significant differences between the mean values of both groups were to be found of the following amino - acids: Alanine, methionine, ornithine, isoleucine and histidine. In the group of the patients correlations of the free amino acids to both serumlipids and blood -- glucose could be calculated with significant results in a certain number of amino-acids. The results may suppose that the changes in the metabolism of atherosclerotic patients do not only effect the lipids and carbohydrates, but as well the free amino-acids."}
{"id": "PMID:14557", "title": "Halothane depresses baroreflex control of heart rate in man.", "content": "Baroreflex control of heart rate was determined during three awake control situations and during two depths of halothane anesthesia in man. Baroreflex function was quantiated by calculating the pressor test slope from the R-R interval change on the ECG produced by a pharmacologically induced pressor response. During the three awake control situations the subjects breathed room air or 100 per cent O2 spontaneously or 100 per cent O2 with ventilation controlled. Mean (+/- SD) slopes obtained were 15.1 +/- 4.5, 15.6 +/- 6.8 and 18.4 +/- 9.9, respectively. No significant difference in baroreflex function slope was observed. During light halothane anesthesia (0.7 per cent endtidal) baroreflex function was significantly depressed (mean slope = 2.5 +/- 1.5), and it was abolished at 1.1 per cent end-tidal halothane (mean slope = 0.03 +/- 0.04). It is concluded that halothane anesthesia produces depression of baroreflex control of heart rate in man.", "contents": "Halothane depresses baroreflex control of heart rate in man. Baroreflex control of heart rate was determined during three awake control situations and during two depths of halothane anesthesia in man. Baroreflex function was quantiated by calculating the pressor test slope from the R-R interval change on the ECG produced by a pharmacologically induced pressor response. During the three awake control situations the subjects breathed room air or 100 per cent O2 spontaneously or 100 per cent O2 with ventilation controlled. Mean (+/- SD) slopes obtained were 15.1 +/- 4.5, 15.6 +/- 6.8 and 18.4 +/- 9.9, respectively. No significant difference in baroreflex function slope was observed. During light halothane anesthesia (0.7 per cent endtidal) baroreflex function was significantly depressed (mean slope = 2.5 +/- 1.5), and it was abolished at 1.1 per cent end-tidal halothane (mean slope = 0.03 +/- 0.04). It is concluded that halothane anesthesia produces depression of baroreflex control of heart rate in man."}
{"id": "PMID:14563", "title": "[Neuroleptics and microsurgery of the ear].", "content": "In the field of research into new methods, we attempted to determine the primary effect, i.e. neuroleptic effects following the intensity of reactions to stimulation in patients undergoing microsurgery of the ear, comparing in particular the quantities of analgesic necessary and used during general anesthetic to ensure both clinically visible protection and, above all, suppression of the effects of stimulation at the level of recordings of arterial and venous pressures. This permits, in our opinion, one to evaluate the dose necessary but also, determine whether or not a drug belongs to the category of neuroleptics which are interesting for the anesthetist.", "contents": "[Neuroleptics and microsurgery of the ear]. In the field of research into new methods, we attempted to determine the primary effect, i.e. neuroleptic effects following the intensity of reactions to stimulation in patients undergoing microsurgery of the ear, comparing in particular the quantities of analgesic necessary and used during general anesthetic to ensure both clinically visible protection and, above all, suppression of the effects of stimulation at the level of recordings of arterial and venous pressures. This permits, in our opinion, one to evaluate the dose necessary but also, determine whether or not a drug belongs to the category of neuroleptics which are interesting for the anesthetist."}
{"id": "PMID:14564", "title": "[Controlled arterial hypotension produced by nitroprusside combined with neuroleptics].", "content": "Ganglioplegic drugs, including trimetaphan, have been imperfect agents of arterial hypotension, liable to produce tachyphylaxis, and not blocking intercurrent attacks of adrenergic hypertension the dose is inconstant and reversibility sometimes doubtful. The association of neuroleptics, in particulier promazines, permits an appreciable economy in dosage, stabilises the curves of hypotension, with the disadvantage of blocking normalisation of blood pressure. Sodium nitroprusside does not have the disadvantage of ganglioplegic drugs. Although usable alone, the blood pressure graphs sometimes have a certain instability mainly due to the difficulty of regulating the ideal perfusion flow rate. The authors show that the association of neuroleptic drugs has here also an effect of economy of dosage and facilitates the rise in blood pressure. Verification of reinforcement of the effect of sodium nitroprusside by chlorpromazine, acepromazine and levomepromazine was carried out in the dog. The authors show significant graphs.", "contents": "[Controlled arterial hypotension produced by nitroprusside combined with neuroleptics]. Ganglioplegic drugs, including trimetaphan, have been imperfect agents of arterial hypotension, liable to produce tachyphylaxis, and not blocking intercurrent attacks of adrenergic hypertension the dose is inconstant and reversibility sometimes doubtful. The association of neuroleptics, in particulier promazines, permits an appreciable economy in dosage, stabilises the curves of hypotension, with the disadvantage of blocking normalisation of blood pressure. Sodium nitroprusside does not have the disadvantage of ganglioplegic drugs. Although usable alone, the blood pressure graphs sometimes have a certain instability mainly due to the difficulty of regulating the ideal perfusion flow rate. The authors show that the association of neuroleptic drugs has here also an effect of economy of dosage and facilitates the rise in blood pressure. Verification of reinforcement of the effect of sodium nitroprusside by chlorpromazine, acepromazine and levomepromazine was carried out in the dog. The authors show significant graphs."}
{"id": "PMID:14565", "title": "[Neuroleptanalgesia as the anesthesia in pediatric surgery].", "content": "In work carried out over a period of two years in the department of anesthetics and intensive care of the Saint-Etienne University Hospital, the authors report their experience of neuroleptanalgesia using droperidol-dextromoramide in children in 104 cases. The observations may be divided up into 2 groups: - 1 group of children below the age of 2 years; - 1 group of children from 2 to 10 years. This study showed the side-effects and complications common to both groups, in particular, the extrapyramidal syndrome. Furthermore, the authors present their technique of administration.", "contents": "[Neuroleptanalgesia as the anesthesia in pediatric surgery]. In work carried out over a period of two years in the department of anesthetics and intensive care of the Saint-Etienne University Hospital, the authors report their experience of neuroleptanalgesia using droperidol-dextromoramide in children in 104 cases. The observations may be divided up into 2 groups: - 1 group of children below the age of 2 years; - 1 group of children from 2 to 10 years. This study showed the side-effects and complications common to both groups, in particular, the extrapyramidal syndrome. Furthermore, the authors present their technique of administration."}
{"id": "PMID:14566", "title": "[Place of neuroleptics in geriatric anesthesia].", "content": "The elderly show changes in various parenchymas linked to the process of ageing. Pathological abnormalities may be added to this picture leading to physiopathology peculiar to the aged. In relation to special problems raised by this background, the advantages and disadvantages of N.L.A. are discussed. The authors refer to an experiment in the Department of Anesthetics and Intensive Care in Cr\u00e9teil.", "contents": "[Place of neuroleptics in geriatric anesthesia]. The elderly show changes in various parenchymas linked to the process of ageing. Pathological abnormalities may be added to this picture leading to physiopathology peculiar to the aged. In relation to special problems raised by this background, the advantages and disadvantages of N.L.A. are discussed. The authors refer to an experiment in the Department of Anesthetics and Intensive Care in Cr\u00e9teil."}
{"id": "PMID:14567", "title": "[Current place of neuroleptics in cardiac surgery under extracorporeal circulation. Cardiovascular effects of different combinations].", "content": "We have been using narconeuroleptanalgesia for anesthesia in cardiac surgery under extra-corporeal circulation since 1969, and we have carried out about 3,500 anesthetics of this type on the 1st of October 1975. For all these anesthetics, the neuroleptic used was droperidol. The other components were: - in the case of the narcotic, penthiobarbital, then more recently Alfatesine; - in the case of the analgesic, either dextromoramide or phenoperidine or Fentanyl; in the case of the curare derivative, D, tubocurarine, and above all, pancuronium dibromide. The advantages of neuroleptanalgesia for such surgery seemed to us mainly: - greater cardio-vascular stability in patients with a heart lesion; - the possibility of better control of cardiac output, i.e. by fillingor by inotropic drugs, thanks to the relative vasoplegia produced by the neuroleptic. Finally, in a recent study, we attempted to determine the hemodynamic effect of droperidol and its association on various analgesic drugs measuring in a few patients the cardiac output, the peripheral resistances the the circulating blood volume. We will report the preliminary results of this study.", "contents": "[Current place of neuroleptics in cardiac surgery under extracorporeal circulation. Cardiovascular effects of different combinations]. We have been using narconeuroleptanalgesia for anesthesia in cardiac surgery under extra-corporeal circulation since 1969, and we have carried out about 3,500 anesthetics of this type on the 1st of October 1975. For all these anesthetics, the neuroleptic used was droperidol. The other components were: - in the case of the narcotic, penthiobarbital, then more recently Alfatesine; - in the case of the analgesic, either dextromoramide or phenoperidine or Fentanyl; in the case of the curare derivative, D, tubocurarine, and above all, pancuronium dibromide. The advantages of neuroleptanalgesia for such surgery seemed to us mainly: - greater cardio-vascular stability in patients with a heart lesion; - the possibility of better control of cardiac output, i.e. by fillingor by inotropic drugs, thanks to the relative vasoplegia produced by the neuroleptic. Finally, in a recent study, we attempted to determine the hemodynamic effect of droperidol and its association on various analgesic drugs measuring in a few patients the cardiac output, the peripheral resistances the the circulating blood volume. We will report the preliminary results of this study."}
{"id": "PMID:14569", "title": "[Neuroplegia in cranial and cranio-thoracic injuries].", "content": "During severe head injuries, the reaction to the cerebral lesion is intense and characterised by a disturbance which is automatic, vasomotor and endocrine. Associated with general ventilatory and nutritional resuscitation, neuroplegia occupies in this pathology, aplace of choice. Cranio-thoracic traumas raise more complex problems owing to different ventilatory requirements, depending on whether the lesion is of the brain or thorax. One must therefore, find a compromise between the depression which necessarily occurs during a too intense autonomic reaction, and the ventilatory requirements created by the thoracic injury. In all cases, the micro-circulatory improvement produced by neuroplegic drugs is probably favourable. The authors report their experience of eighty severe cranio-thoracic traumas, over a period of thirty months, submitted to treatment including neuroplegics.", "contents": "[Neuroplegia in cranial and cranio-thoracic injuries]. During severe head injuries, the reaction to the cerebral lesion is intense and characterised by a disturbance which is automatic, vasomotor and endocrine. Associated with general ventilatory and nutritional resuscitation, neuroplegia occupies in this pathology, aplace of choice. Cranio-thoracic traumas raise more complex problems owing to different ventilatory requirements, depending on whether the lesion is of the brain or thorax. One must therefore, find a compromise between the depression which necessarily occurs during a too intense autonomic reaction, and the ventilatory requirements created by the thoracic injury. In all cases, the micro-circulatory improvement produced by neuroplegic drugs is probably favourable. The authors report their experience of eighty severe cranio-thoracic traumas, over a period of thirty months, submitted to treatment including neuroplegics."}
{"id": "PMID:14570", "title": "[Place of neuroleptics in neurosurgical anesthesia-resuscitation].", "content": "The interest of neuroleptics in neurosurgery should be examined in the light of physiopathological and pharmacological data concerning cerebral circulatory autoregulation and intracranial pressure. The fairly favourable conclusions permit one to consider their wide use justified, especially, by the feeble hypnogenic effects, without any marked disturbance of the E.E.G., associated with an anticatecholaminergic and stabilizing effect on the autonomic nervous system. They therefore occupy a place of choice, in particular during induction of anesthesia in high risk patients, during operations requiring neurological or continuous E.E.G. investigations, in surgery of intracranial aneurysm and, finally, to obtain sedation and post-operative autonomic control.", "contents": "[Place of neuroleptics in neurosurgical anesthesia-resuscitation]. The interest of neuroleptics in neurosurgery should be examined in the light of physiopathological and pharmacological data concerning cerebral circulatory autoregulation and intracranial pressure. The fairly favourable conclusions permit one to consider their wide use justified, especially, by the feeble hypnogenic effects, without any marked disturbance of the E.E.G., associated with an anticatecholaminergic and stabilizing effect on the autonomic nervous system. They therefore occupy a place of choice, in particular during induction of anesthesia in high risk patients, during operations requiring neurological or continuous E.E.G. investigations, in surgery of intracranial aneurysm and, finally, to obtain sedation and post-operative autonomic control."}
{"id": "PMID:14571", "title": "[Very-high-dose droperidol and brain stem injuries].", "content": "Treating four comatose children with severe injuries of the brain stem, suffering from severe autonomic disorders without any indications for neurosurgery, we were led to increase gradually the doses of neuroleptics used as basis of treatment, the main one being Droperidol. The increase in dosage, often reaching very high doses, was rendered necessary owing to a phenomenon comparable to that of addiction, a steadily increasing dose was necessary each day to obtain the same beneficial effects of autonomic stabilization. A complete cure was obtained on each occasion, at the end of a coma varying between 20 days and two and a half months. The extreme case was the last case in which we were led to give in a single day, 7 grams of the drug to a 12 years old child, who completely recovered his motor and intellectual functions after a coma lasting thirty five days. Comparison of the four cases led us to suppose that the result is all the better when treatment with neuroleptics is started soon after the accident, in low dosage but regularly increased without fixing any other ceiling than the effect obtained, the toxicity of Droperidol seemed to us very low, even in very high dosage, provided the conditions of gradualness are respected. Although it is classical to say that the prognosis of trauma of the brain stem is more favourable in children than in adults, we are certain that such treatment contributed considerably to avoid a fatal issue or chronic invalidism.", "contents": "[Very-high-dose droperidol and brain stem injuries]. Treating four comatose children with severe injuries of the brain stem, suffering from severe autonomic disorders without any indications for neurosurgery, we were led to increase gradually the doses of neuroleptics used as basis of treatment, the main one being Droperidol. The increase in dosage, often reaching very high doses, was rendered necessary owing to a phenomenon comparable to that of addiction, a steadily increasing dose was necessary each day to obtain the same beneficial effects of autonomic stabilization. A complete cure was obtained on each occasion, at the end of a coma varying between 20 days and two and a half months. The extreme case was the last case in which we were led to give in a single day, 7 grams of the drug to a 12 years old child, who completely recovered his motor and intellectual functions after a coma lasting thirty five days. Comparison of the four cases led us to suppose that the result is all the better when treatment with neuroleptics is started soon after the accident, in low dosage but regularly increased without fixing any other ceiling than the effect obtained, the toxicity of Droperidol seemed to us very low, even in very high dosage, provided the conditions of gradualness are respected. Although it is classical to say that the prognosis of trauma of the brain stem is more favourable in children than in adults, we are certain that such treatment contributed considerably to avoid a fatal issue or chronic invalidism."}
{"id": "PMID:14572", "title": "[Neuroleptics and continuous measurement of intracranial pressure].", "content": "Neurosurgical patients, whether injured or not, have benefited in recent years from a new technique of supervision, measurement of thr intracranial pressure (ICP). Thus, measurement of a pressure figure and its course, gives precious information, both diagnostic and therapeutic. Various techniques of measurement are now proposed. We chose, for special reasons, measurement of the ICP within the ventricle. A catheter is introduced into the ventricle through a trephine hole. It is linked by a liquid column to a recording system (cathode oscilloscope, ink writer or magnetic tape). A slow inscriber permits continuous recording of the ICP for several days or even weeks. In view of the narrow dependency of the ICP on other physiological parameters, it seemed to us essential to record simultaneously 5 other parameters, the temperature, the blood pressure, the central venous pressure, the heart rate and the respiratory ventilation, by measurement of FeCO2 (capnography). Several forms of treatment have been proposed to bring down a raised ICP (greater than 15 mm Hg), e.g. osmotic diuresis, hyperventilation, corticosteroid therapy. Removal of CSF by ventriculalar catheter, sometimes permits one to pass over the critical period. It was in this background that we attempted to analyse the effect of neuroleptics on the ICP, without attempting to explain their mechanism of action. Our study was of 10 patients with cranial trauma, of both sexes, aged from 14 to 60 years. The intracranial pressure was measured within the ventricle and correlated with the other physiological parameters. When the ICP was normal, e.g. primary lesion of the brain stem, administration of neuroleptics such as chlorpromazine 100 mg IV/24 hours, or levopromazine 50 mg IV/24 hours, does not modify the value of the ICP. On the other hand, in the case of raised intracranial pressure due to contusion with cerebral oedema, for example, the administration of neuroleptic drugs seems to provide a very slight reduction in this pressure. It would be interesting to measure, at the same time as the ICP, the cerebral blood flow.", "contents": "[Neuroleptics and continuous measurement of intracranial pressure]. Neurosurgical patients, whether injured or not, have benefited in recent years from a new technique of supervision, measurement of thr intracranial pressure (ICP). Thus, measurement of a pressure figure and its course, gives precious information, both diagnostic and therapeutic. Various techniques of measurement are now proposed. We chose, for special reasons, measurement of the ICP within the ventricle. A catheter is introduced into the ventricle through a trephine hole. It is linked by a liquid column to a recording system (cathode oscilloscope, ink writer or magnetic tape). A slow inscriber permits continuous recording of the ICP for several days or even weeks. In view of the narrow dependency of the ICP on other physiological parameters, it seemed to us essential to record simultaneously 5 other parameters, the temperature, the blood pressure, the central venous pressure, the heart rate and the respiratory ventilation, by measurement of FeCO2 (capnography). Several forms of treatment have been proposed to bring down a raised ICP (greater than 15 mm Hg), e.g. osmotic diuresis, hyperventilation, corticosteroid therapy. Removal of CSF by ventriculalar catheter, sometimes permits one to pass over the critical period. It was in this background that we attempted to analyse the effect of neuroleptics on the ICP, without attempting to explain their mechanism of action. Our study was of 10 patients with cranial trauma, of both sexes, aged from 14 to 60 years. The intracranial pressure was measured within the ventricle and correlated with the other physiological parameters. When the ICP was normal, e.g. primary lesion of the brain stem, administration of neuroleptics such as chlorpromazine 100 mg IV/24 hours, or levopromazine 50 mg IV/24 hours, does not modify the value of the ICP. On the other hand, in the case of raised intracranial pressure due to contusion with cerebral oedema, for example, the administration of neuroleptic drugs seems to provide a very slight reduction in this pressure. It would be interesting to measure, at the same time as the ICP, the cerebral blood flow."}
{"id": "PMID:14573", "title": "[Note on the comparative effects of benzodiazepines and chlorpromazine on intracranial pressure in the dog].", "content": "The neutrality of the butyrophenones on intracranial pressure has been relatively well shown. That of the phenothiazines and benzodiazepine derivatives has been less well established. The authors studied, by a continuous method, the action of chlorpromazine, acepromazine and three benzodiazepines (diazepam, flunitrazepam and chlorazepam) on intracranial pressure and blood pressure in the dog. These substances seem to be definitely neutral on intracranial pressure, more so in the case of the benzodiazepines than for the promazines, the vasomotor action of which was perceptible when seen closely. The authors produce demonstrative graphs, illustrating the correlation of these two pressures.", "contents": "[Note on the comparative effects of benzodiazepines and chlorpromazine on intracranial pressure in the dog]. The neutrality of the butyrophenones on intracranial pressure has been relatively well shown. That of the phenothiazines and benzodiazepine derivatives has been less well established. The authors studied, by a continuous method, the action of chlorpromazine, acepromazine and three benzodiazepines (diazepam, flunitrazepam and chlorazepam) on intracranial pressure and blood pressure in the dog. These substances seem to be definitely neutral on intracranial pressure, more so in the case of the benzodiazepines than for the promazines, the vasomotor action of which was perceptible when seen closely. The authors produce demonstrative graphs, illustrating the correlation of these two pressures."}
{"id": "PMID:14575", "title": "Effect of adrenalectomy in the dog on blood gas tensions and oxygen content.", "content": "Arterial and venous blood gas tensions and pH were determined in 8 dogs during a control interval, while adrenal deficient, and following replacement therapy with corticosteroids. Additionally, erythrocyte 2,3-diphosphoglycerate (DPG) values were measured, and oxygen tension (mm of Hg) when hemoglobin is half-saturated with oxygen (P50) values were calculated. Mixed venous oxygen tension (PVO2), but not arterial oxygen tension (Pao2), decreased significantly (P less than 0.001) during adrenal insufficiency. This change was reflected in a significantly decreased (P less than 0.001) venous oxygen content and a significant increase (P less than 0.001) of the arterial-venous oxygen content difference. Other changes during adrenal insufficiency were nonsignificant decreases in DPG and P50 values. Treatment with corticosteroids for 2 to 3 days resulted in a significant (P less than 0.001) increase in DPG concentrations, a significant (P less than 0.025) increase in P50, and a reduction in the arterial-venous oxygen content difference compared with those values found in the adrenal-deficient dog.", "contents": "Effect of adrenalectomy in the dog on blood gas tensions and oxygen content. Arterial and venous blood gas tensions and pH were determined in 8 dogs during a control interval, while adrenal deficient, and following replacement therapy with corticosteroids. Additionally, erythrocyte 2,3-diphosphoglycerate (DPG) values were measured, and oxygen tension (mm of Hg) when hemoglobin is half-saturated with oxygen (P50) values were calculated. Mixed venous oxygen tension (PVO2), but not arterial oxygen tension (Pao2), decreased significantly (P less than 0.001) during adrenal insufficiency. This change was reflected in a significantly decreased (P less than 0.001) venous oxygen content and a significant increase (P less than 0.001) of the arterial-venous oxygen content difference. Other changes during adrenal insufficiency were nonsignificant decreases in DPG and P50 values. Treatment with corticosteroids for 2 to 3 days resulted in a significant (P less than 0.001) increase in DPG concentrations, a significant (P less than 0.025) increase in P50, and a reduction in the arterial-venous oxygen content difference compared with those values found in the adrenal-deficient dog."}
{"id": "PMID:14576", "title": "Salicylate pulmonary edema: the mechanism in sheep and review of the clinical literature.", "content": "Several clinical reports of salicylate-induced pulmonary edema led us to investigate the mechanism in a chronic unanesthetized sheep preparation. We infused an aspirin-buffer solution intravenously at rates up to 1,200 mg of aspirin per hour and compared effects on lung lymph flow and lymph protein concentration to those seen after mechanical elevation of pulmonary vascular pressures. Aspirin had little effect on lung vascular pressures but caused lung lymph flow to increase an average of greater than twice baseline. Because lymph protein concentrations were higher for a given lymph flow with aspirin than during mechanical pressure elevation, lymph protein (lymph flow X lymph to plasma protein concentration) increased much more with aspirin. Thus, aspirin appears to cause increased permeability to fluid and protein in the pulmonary vascular bed. Aspirin caused arterial PO2 to decrease from 83 +/- 3 SE mm Hg to 74 +/- 3 mm Hg (P less than 0.05) and caused postmortem extravascular lung water to increase. These findings are supported by a review of the clinical literature, indicating that salicylate pulmonary edema in humans is noncardiac in origin and may occur at doses considered therapeutic for some diseases as well as after overdose.", "contents": "Salicylate pulmonary edema: the mechanism in sheep and review of the clinical literature. Several clinical reports of salicylate-induced pulmonary edema led us to investigate the mechanism in a chronic unanesthetized sheep preparation. We infused an aspirin-buffer solution intravenously at rates up to 1,200 mg of aspirin per hour and compared effects on lung lymph flow and lymph protein concentration to those seen after mechanical elevation of pulmonary vascular pressures. Aspirin had little effect on lung vascular pressures but caused lung lymph flow to increase an average of greater than twice baseline. Because lymph protein concentrations were higher for a given lymph flow with aspirin than during mechanical pressure elevation, lymph protein (lymph flow X lymph to plasma protein concentration) increased much more with aspirin. Thus, aspirin appears to cause increased permeability to fluid and protein in the pulmonary vascular bed. Aspirin caused arterial PO2 to decrease from 83 +/- 3 SE mm Hg to 74 +/- 3 mm Hg (P less than 0.05) and caused postmortem extravascular lung water to increase. These findings are supported by a review of the clinical literature, indicating that salicylate pulmonary edema in humans is noncardiac in origin and may occur at doses considered therapeutic for some diseases as well as after overdose."}
{"id": "PMID:14577", "title": "Treatment of brain disease with dietary precursors of neurotransmitters.", "content": "A growing number of brain diseases are characterized by decreased levels of one or more of the neurotransmitters. Recent experimental evidence indicates that nutritional factors strongly influence the regulation of two of these neurotransmitters, serotonin and acetylcholine. As a result, attempts are now being made to treat diseases associated with low levels of serotonin or acetylcholine by administering their dietary precursors, tryptophan and choline, respectively. This treatment may increase the amount of the deficient neurotransmitter at synapses and produce clinical benefit. Such efforts to elevate brain neurotransmitter levels with a naturally occurring precursor represent a new approach in medical therapeutics and will probably continue. We review the scientific basis for such treatment and show that brain levels of serotonin and acetylcholine depend upon the amounts of tryptophan and choline available to the brain; these, in turn, fluctuate according to dietary factors.", "contents": "Treatment of brain disease with dietary precursors of neurotransmitters. A growing number of brain diseases are characterized by decreased levels of one or more of the neurotransmitters. Recent experimental evidence indicates that nutritional factors strongly influence the regulation of two of these neurotransmitters, serotonin and acetylcholine. As a result, attempts are now being made to treat diseases associated with low levels of serotonin or acetylcholine by administering their dietary precursors, tryptophan and choline, respectively. This treatment may increase the amount of the deficient neurotransmitter at synapses and produce clinical benefit. Such efforts to elevate brain neurotransmitter levels with a naturally occurring precursor represent a new approach in medical therapeutics and will probably continue. We review the scientific basis for such treatment and show that brain levels of serotonin and acetylcholine depend upon the amounts of tryptophan and choline available to the brain; these, in turn, fluctuate according to dietary factors."}
{"id": "PMID:14578", "title": "[Rabies glycoprotein purification by isoelectric focusing (author's transl)].", "content": "A glycoprotein was extracted with Triton X100 from rabies virus grown in primary foetal bovine kidney cells. This glycoprotein was further purified by iso electro focusing and showed a major peak at pH 7,0 and a smaller peak at pH 4,6. Purified fractions were migrated on polyacrylamide gels and assayed for immunogenicity.", "contents": "[Rabies glycoprotein purification by isoelectric focusing (author's transl)]. A glycoprotein was extracted with Triton X100 from rabies virus grown in primary foetal bovine kidney cells. This glycoprotein was further purified by iso electro focusing and showed a major peak at pH 7,0 and a smaller peak at pH 4,6. Purified fractions were migrated on polyacrylamide gels and assayed for immunogenicity."}
{"id": "PMID:14579", "title": "[Studies on the mechanism of interaction of glutaraldehyde with microorganisms (author's transl)].", "content": "The antimicrobial action of glutaraldehyde on Candida lipolytica increases with reagent concentration, pH and duration of contact. The simultaneous study of the size distribution of the particles shows an agglutination of the cells. This result is confirmed by direct observation of the cells by electron microscopy. Cell agglutination also occurs with other microorganisms (Saccharomyces carlsbergensis, Bacillus megaterium, Escherichia coli) and increases their settling rate. The formation of such intercellular bonds seems to confirm the hypothesis of a preferential action of glutaraldehyde on the outer layers of the cells. The effect of pH on the antimicrobial action of glutaraldehyde is accounted for by the fact that this reagent does not act, under neutral and alcaline conditions, as a dialdehyde but as an unsaturated polymer. This mechanism also accounts for various observations made on microorganisms-glutaraldehyde interactions.", "contents": "[Studies on the mechanism of interaction of glutaraldehyde with microorganisms (author's transl)]. The antimicrobial action of glutaraldehyde on Candida lipolytica increases with reagent concentration, pH and duration of contact. The simultaneous study of the size distribution of the particles shows an agglutination of the cells. This result is confirmed by direct observation of the cells by electron microscopy. Cell agglutination also occurs with other microorganisms (Saccharomyces carlsbergensis, Bacillus megaterium, Escherichia coli) and increases their settling rate. The formation of such intercellular bonds seems to confirm the hypothesis of a preferential action of glutaraldehyde on the outer layers of the cells. The effect of pH on the antimicrobial action of glutaraldehyde is accounted for by the fact that this reagent does not act, under neutral and alcaline conditions, as a dialdehyde but as an unsaturated polymer. This mechanism also accounts for various observations made on microorganisms-glutaraldehyde interactions."}
{"id": "PMID:14586", "title": "[Familial palmo-plantar keratoderma with epidermolytic hyperkeratosis (author's transl)].", "content": "Three cases of palmo-plantar keratoderma coming from three different families are reported; Clinical features were those of Thost-Unna's disease; histo-pathological and ultrastructural aspects resembled those of the epidermolytic hyperkeratosis. The literature, 13 cases within 7 families with the same clinical and histopathological characteristics (though without study of the ultrastructure), have been reported. The authors propose to term \"familial palmo-plantar keratoderma with epidermolytic hyperkeratosis\", those cases of palmo-plantar keratoderma with dominant autosomal transmission and the histopathological aspects of the epidermolytic hyperkeratosis (Frost and Van Scott). The relationship of this disease with the naevus unius lateris and the bullous ichtyosiform hyperkeratosis are discussed. All three diseases could represent various phenotypical aspects of the same genetic abnormality of the keratinization process.", "contents": "[Familial palmo-plantar keratoderma with epidermolytic hyperkeratosis (author's transl)]. Three cases of palmo-plantar keratoderma coming from three different families are reported; Clinical features were those of Thost-Unna's disease; histo-pathological and ultrastructural aspects resembled those of the epidermolytic hyperkeratosis. The literature, 13 cases within 7 families with the same clinical and histopathological characteristics (though without study of the ultrastructure), have been reported. The authors propose to term \"familial palmo-plantar keratoderma with epidermolytic hyperkeratosis\", those cases of palmo-plantar keratoderma with dominant autosomal transmission and the histopathological aspects of the epidermolytic hyperkeratosis (Frost and Van Scott). The relationship of this disease with the naevus unius lateris and the bullous ichtyosiform hyperkeratosis are discussed. All three diseases could represent various phenotypical aspects of the same genetic abnormality of the keratinization process."}
{"id": "PMID:14588", "title": "Comparison of thiopentone versus althesin for caesarean section.", "content": "Thiopentone and Althesin were compared in 50 patients undergoing general anaesthesia for Caesarean section. The patients were divided into group A (24 mothers) were thiopentone (3.5 mg/kg) was used for induction and group B (26 mothers) where Althesin (80 mu1/kg) was employed. Blood samples for estimating the maternal and umbilical venous and arterial blood pH, pCO2, BD and pO2 were taken at the time of delivery. The clinical condition of the newborn were estimated by the Apgar score. Postoperatively the mothers were interviewed about thei subjective opinion concerning the anaesthesia. The interview showed equal acceptance of both induction agents. The umbilical venous and arterial pH, pCO2 and BD were well within the normal physiological range and there was no significant intergroup difference. The only significant differences were the lower umbilical venous and arterial pO2 values in the Althesin group. The clinical condition of the newborn (Apgar score) showed no significant difference between the two groups.", "contents": "Comparison of thiopentone versus althesin for caesarean section. Thiopentone and Althesin were compared in 50 patients undergoing general anaesthesia for Caesarean section. The patients were divided into group A (24 mothers) were thiopentone (3.5 mg/kg) was used for induction and group B (26 mothers) where Althesin (80 mu1/kg) was employed. Blood samples for estimating the maternal and umbilical venous and arterial blood pH, pCO2, BD and pO2 were taken at the time of delivery. The clinical condition of the newborn were estimated by the Apgar score. Postoperatively the mothers were interviewed about thei subjective opinion concerning the anaesthesia. The interview showed equal acceptance of both induction agents. The umbilical venous and arterial pH, pCO2 and BD were well within the normal physiological range and there was no significant intergroup difference. The only significant differences were the lower umbilical venous and arterial pO2 values in the Althesin group. The clinical condition of the newborn (Apgar score) showed no significant difference between the two groups."}
{"id": "PMID:14589", "title": "[Optimization of conditions for determining the activity of amphotericin B].", "content": "The effect of incubation temperature, pH  and medium composition on the size of the growth inhibitions zones, clearance of their borders and slope of the dose-response curve in determin ation of the biological activity of amphotericin B by the agar-diffusion method using Candida scotti, Tul-1 as the test-microbe was studied. The composition of the medium providing optimal conditions for the activity assay according to the sone size and clearness was developed. When the above medium was used for determination of the biological activity of amphotericin B, the standard deviatioos of the assay results, as well as the average results obtained at an interval of 1 month were 1.5 times lower than with the use of the medium proposed at an interval of 1 month were 1.5 times lower than with the use of the medium proposed in Specification 42 No. 3857-70. At the same time the average results of the assay on both media coincided.", "contents": "[Optimization of conditions for determining the activity of amphotericin B]. The effect of incubation temperature, pH  and medium composition on the size of the growth inhibitions zones, clearance of their borders and slope of the dose-response curve in determin ation of the biological activity of amphotericin B by the agar-diffusion method using Candida scotti, Tul-1 as the test-microbe was studied. The composition of the medium providing optimal conditions for the activity assay according to the sone size and clearness was developed. When the above medium was used for determination of the biological activity of amphotericin B, the standard deviatioos of the assay results, as well as the average results obtained at an interval of 1 month were 1.5 times lower than with the use of the medium proposed at an interval of 1 month were 1.5 times lower than with the use of the medium proposed in Specification 42 No. 3857-70. At the same time the average results of the assay on both media coincided."}
{"id": "PMID:14600", "title": "The phenol oxidases of the ascomycete Podospora anserina. XII. Affinity of laccases II and III to substrates with different substitution patterns.", "content": "For the low molecular weight laccases II and III of Podospora anserina the kinetic parameters Michaelis constant (KM) and maximum reaction velocity (V) were determined polarographically under pH optimum conditions for representative substrates of different substitution patterns. Laccase II showed two peaks in its pH optimum curve, each with a different substrate specificity, indicating structural differences to laccase III which exhibits only one broad peak. Under optimum conditions the affinities of various substrates are determined by their substitution patterns: high affinity for simple o- and p-diphenols, low affinity for m-henols. The maximal velocity remains largely uninfluenced. This study of the effect of substitution on substrate utilization leads to the assumption that there is no specific reactive site for m-phenols in either laccase. Oxidation of m-phenols, however, takes only place at high pH values.", "contents": "The phenol oxidases of the ascomycete Podospora anserina. XII. Affinity of laccases II and III to substrates with different substitution patterns. For the low molecular weight laccases II and III of Podospora anserina the kinetic parameters Michaelis constant (KM) and maximum reaction velocity (V) were determined polarographically under pH optimum conditions for representative substrates of different substitution patterns. Laccase II showed two peaks in its pH optimum curve, each with a different substrate specificity, indicating structural differences to laccase III which exhibits only one broad peak. Under optimum conditions the affinities of various substrates are determined by their substitution patterns: high affinity for simple o- and p-diphenols, low affinity for m-henols. The maximal velocity remains largely uninfluenced. This study of the effect of substitution on substrate utilization leads to the assumption that there is no specific reactive site for m-phenols in either laccase. Oxidation of m-phenols, however, takes only place at high pH values."}
{"id": "PMID:14601", "title": "Comparative studies of lactic acid dehydrogenases in lactic acid bacteria. I. Purification and kinetics of the allosteric L-lactic acid dehydrogenase from Lactobacillus casei ssp. casei and Lactobacillus curvatus.", "content": "The stability, pH-dependence and kinetic properties of the Mn2+ and FDP-activated NAD-dependent lactic acid dehydrogenases from Lactobacillus casei ssp. casei (ATCC 393) and L. curvatus (DSM 20010) were studied after the enzymes were purified to homogeneity by affinity chromatography. Both enzymes are virtually unidirectional, catalysing efficiency only the reduction of pyruvate. They are similar with respect to the effector requirement and pH-optimum. They differ, however, in their electrophoretic mobility, heat stability, pH-dependence of the Mn2+ requirement and several kinetic properties. It is suggested that most of these differences are caused by differences of the negative charges in the vicinity of the FDP-binding site or the site responsible for the interaction of the subunits of the enzymatically active oligomeres.", "contents": "Comparative studies of lactic acid dehydrogenases in lactic acid bacteria. I. Purification and kinetics of the allosteric L-lactic acid dehydrogenase from Lactobacillus casei ssp. casei and Lactobacillus curvatus. The stability, pH-dependence and kinetic properties of the Mn2+ and FDP-activated NAD-dependent lactic acid dehydrogenases from Lactobacillus casei ssp. casei (ATCC 393) and L. curvatus (DSM 20010) were studied after the enzymes were purified to homogeneity by affinity chromatography. Both enzymes are virtually unidirectional, catalysing efficiency only the reduction of pyruvate. They are similar with respect to the effector requirement and pH-optimum. They differ, however, in their electrophoretic mobility, heat stability, pH-dependence of the Mn2+ requirement and several kinetic properties. It is suggested that most of these differences are caused by differences of the negative charges in the vicinity of the FDP-binding site or the site responsible for the interaction of the subunits of the enzymatically active oligomeres."}
{"id": "PMID:14602", "title": "Therapeutic usefulness of propoxyphene napsylate in narcotic addiction.", "content": "The maximum doses of propoxyphene napsylate used to treat heroin addicts produce a degree of morphine-like activity equal to that produced by 20 to 25 mg/day of subcutaneously given morphine or 10 mg/day orally given methadone. This degree of activity wound be sufficient to ameliorate abstinence even in patients dependent on large doses of narcotics--an observation that supports the utility of propoxyphene napsylate in detoxification. On the other hand, only patients taking 10 mg/day or less of parenterally administered heroin could be maintained on maximum subtoxic levels of propoxyphene napsylate without abstinence signs or symptoms suggesting that propoxyphene napsylate would be less useful in maintenance therapy.", "contents": "Therapeutic usefulness of propoxyphene napsylate in narcotic addiction. The maximum doses of propoxyphene napsylate used to treat heroin addicts produce a degree of morphine-like activity equal to that produced by 20 to 25 mg/day of subcutaneously given morphine or 10 mg/day orally given methadone. This degree of activity wound be sufficient to ameliorate abstinence even in patients dependent on large doses of narcotics--an observation that supports the utility of propoxyphene napsylate in detoxification. On the other hand, only patients taking 10 mg/day or less of parenterally administered heroin could be maintained on maximum subtoxic levels of propoxyphene napsylate without abstinence signs or symptoms suggesting that propoxyphene napsylate would be less useful in maintenance therapy."}
{"id": "PMID:14603", "title": "Antidepressants and the muscarinic acetylcholine receptor.", "content": "Several tricyclic antidepressants have been assessed for their potency in binding to the muscarinic acetylcholine receptor of brain and intestine. Amitriptyline hydrochloride is about ten times as potent as imipramine hydrochloride. Dimethylated drugs are more potent than monomethylated ones. The relative anticholinergic activities of tricyclic antidepressants have implications for their use in patients who might be affected adversely by anticholinergic effects.", "contents": "Antidepressants and the muscarinic acetylcholine receptor. Several tricyclic antidepressants have been assessed for their potency in binding to the muscarinic acetylcholine receptor of brain and intestine. Amitriptyline hydrochloride is about ten times as potent as imipramine hydrochloride. Dimethylated drugs are more potent than monomethylated ones. The relative anticholinergic activities of tricyclic antidepressants have implications for their use in patients who might be affected adversely by anticholinergic effects."}
{"id": "PMID:14599", "title": "[Acute sepsis caused by \"Gaffkya tetragena\" in adult with hypogammaglobulinemia (author's transl)].", "content": "A case of acute sepsis caused by Gaffkya tetragena in an adult with acquired hypogammaglobulinemia has been described. The Authors pointout the importance that particular conditions of disreactivity and/or of immunodeficiency can play in the acquistion of pathogenicity by Gaffkya tetragena. In the case under discussion a high deficit of IgG and IgA was demonstrable, which had previously caused a long series of infective bacterial diseases.", "contents": "[Acute sepsis caused by \"Gaffkya tetragena\" in adult with hypogammaglobulinemia (author's transl)]. A case of acute sepsis caused by Gaffkya tetragena in an adult with acquired hypogammaglobulinemia has been described. The Authors pointout the importance that particular conditions of disreactivity and/or of immunodeficiency can play in the acquistion of pathogenicity by Gaffkya tetragena. In the case under discussion a high deficit of IgG and IgA was demonstrable, which had previously caused a long series of infective bacterial diseases."}
{"id": "PMID:14606", "title": "[Clinical trial with barbexaclone in epilepsies].", "content": "A open clinic assay with barbexaclone which is an association of phenobarvital with light stimulant of the central nervous system (tau-l-ciclohexil-2-methil-aminopropane) for the treatment of epileptic disorders is reported. The authors have studied 40 patients aged between 0-12 years of age, of both sexes, all of them having convulsive seizures of the Grand Mal type associated or not to other epileptic manifestations. After analysing the different aspects of the group they consider satisfactory the results obtained: very good or good in 82,5% of the cases.", "contents": "[Clinical trial with barbexaclone in epilepsies]. A open clinic assay with barbexaclone which is an association of phenobarvital with light stimulant of the central nervous system (tau-l-ciclohexil-2-methil-aminopropane) for the treatment of epileptic disorders is reported. The authors have studied 40 patients aged between 0-12 years of age, of both sexes, all of them having convulsive seizures of the Grand Mal type associated or not to other epileptic manifestations. After analysing the different aspects of the group they consider satisfactory the results obtained: very good or good in 82,5% of the cases."}
{"id": "PMID:14607", "title": "Simultaneous determination of skeletal muscle fiber, types I, IIA, and IIB by histochemistry.", "content": "We describe a simplified technique for the histochemical determination of three fiber types from a single section of skeletal muscle. Preincubation in a solution of formaldehyde, glycine, and calcium followed by routine myofibrillar adenosine triphosphatase (ATPase) incubation clearly differentiates type I, type IIA, and IIB fibers in human, rat, rabbit, and porcine muscle. In addition, glycine-formaldehyde-calcium preincubation offers better preservation of cytoarchitecture and standardization of incubation time.", "contents": "Simultaneous determination of skeletal muscle fiber, types I, IIA, and IIB by histochemistry. We describe a simplified technique for the histochemical determination of three fiber types from a single section of skeletal muscle. Preincubation in a solution of formaldehyde, glycine, and calcium followed by routine myofibrillar adenosine triphosphatase (ATPase) incubation clearly differentiates type I, type IIA, and IIB fibers in human, rat, rabbit, and porcine muscle. In addition, glycine-formaldehyde-calcium preincubation offers better preservation of cytoarchitecture and standardization of incubation time."}
{"id": "PMID:14608", "title": "Variations in the spectrum of desulfoviridin from Desulfovibrio gigas.", "content": "Desulfoviridin preparations from D. gigas showed variations in the position of the absorption maximum the beta-peak) in the 580-nm region of the specturm. On treatment with Na2S2O4 a preparation with a beta-peak at 585 nm was affected rapidly, the 585-nm peak shifting to the 596-nm region; this was partially reversed by K3Fe(CN)6. Treatment of the original preparation with K3Fe(CN)6 resulted in a shift of the beta-peak to 582-583 nm. Desulfoviridins with beta-peaks from 580 to 583 nm were not rapidly affected by Na2S2O4. The spectrum of the chromophore of desulfoviridin way also affected by Na2S2O4 with the peak at 587 nm shifting to 597 nm; this effect was completely reversed by oxygen. There was no evidence to show that spectral variations in desulfoviridin preparations were due to the loss or acquisition of metal ions during growth or to the selection of mutants containing spectrally different desulfoviridins. It is suggested that during biosynethesis oal detachment of the chromophore, thus causing a change towards the spectral properites of the detached chromophore.", "contents": "Variations in the spectrum of desulfoviridin from Desulfovibrio gigas. Desulfoviridin preparations from D. gigas showed variations in the position of the absorption maximum the beta-peak) in the 580-nm region of the specturm. On treatment with Na2S2O4 a preparation with a beta-peak at 585 nm was affected rapidly, the 585-nm peak shifting to the 596-nm region; this was partially reversed by K3Fe(CN)6. Treatment of the original preparation with K3Fe(CN)6 resulted in a shift of the beta-peak to 582-583 nm. Desulfoviridins with beta-peaks from 580 to 583 nm were not rapidly affected by Na2S2O4. The spectrum of the chromophore of desulfoviridin way also affected by Na2S2O4 with the peak at 587 nm shifting to 597 nm; this effect was completely reversed by oxygen. There was no evidence to show that spectral variations in desulfoviridin preparations were due to the loss or acquisition of metal ions during growth or to the selection of mutants containing spectrally different desulfoviridins. It is suggested that during biosynethesis oal detachment of the chromophore, thus causing a change towards the spectral properites of the detached chromophore."}
{"id": "PMID:14609", "title": "An alternative coupling procedure for preparing activated sepharose for affinity chromatography of penicillinase.", "content": "Most applications of affinity chromatography employ the cyanogen bromide activation scheme first devised by Ax\u00e8n et al. (1967). Porath and Sunberg (1972) reported an alternative procedure in which phloroglucinol and divinylsulphone are used in activating reactions. The advantages of this scheme and parameters relevant to the activating reactions are reported here. Conditions for the attachment of various ligand molecules to sepharose using a divinylsulphone activation method are defined, and a comparison with cyanogen bromide activating and coupling techniques is drawn. alpha-Chymotrypsin is immobilized by covalent attachment to activated sepharose. The optimum coupling pH is 8-0-8-6 and the reaction is virtually complete after 20 h at room temperature. Conjugates containing as much as 2 g of enzyme per gram dry weight of polymer were obtained. The immobilized enzyme retained 41% of the free enzymic activity. An affinity column of divinylsulphone-activated methicillin-sepharose was used to demonstrate the reversible adsorption of penicillinase.", "contents": "An alternative coupling procedure for preparing activated sepharose for affinity chromatography of penicillinase. Most applications of affinity chromatography employ the cyanogen bromide activation scheme first devised by Ax\u00e8n et al. (1967). Porath and Sunberg (1972) reported an alternative procedure in which phloroglucinol and divinylsulphone are used in activating reactions. The advantages of this scheme and parameters relevant to the activating reactions are reported here. Conditions for the attachment of various ligand molecules to sepharose using a divinylsulphone activation method are defined, and a comparison with cyanogen bromide activating and coupling techniques is drawn. alpha-Chymotrypsin is immobilized by covalent attachment to activated sepharose. The optimum coupling pH is 8-0-8-6 and the reaction is virtually complete after 20 h at room temperature. Conjugates containing as much as 2 g of enzyme per gram dry weight of polymer were obtained. The immobilized enzyme retained 41% of the free enzymic activity. An affinity column of divinylsulphone-activated methicillin-sepharose was used to demonstrate the reversible adsorption of penicillinase."}
{"id": "PMID:14610", "title": "Studies on the apoproteins of the major lipoprotein of the yolk of hen's eggs II. The dimer-tetramer transition of apovitellenin I.", "content": "Further studies have been made of the physical properties of hen's apovitellenin I, the principal low-molecular-weight protein from the high-lipid low density lipoprotein of the yolk of hen's eggs. The methods used included chromatography, sedimentation, viscosity, optical rotation, and spin labelling; the solvents used were aqueous urea, and, for some experiments, aqueous formamide. It is concluded that a neutral pH the protein is present in these solvents as an aggregate of molecular weight 36000 corresponding to a tetramer. Below about pH 4-5 solutions of the tetramer increased greatly in viscosity; furthermore, a covalently bound spin label increased in mobility. These changes were reversible and were apparently the result of dissociation of the tetramer to a dimer. This disociation did not involve a change in the proportion of alpha-helix. In contrast to the results of previous experiments, it now seems probably that the apovitellenin I dimer is stabilized by an interchain disulphide bond.", "contents": "Studies on the apoproteins of the major lipoprotein of the yolk of hen's eggs II. The dimer-tetramer transition of apovitellenin I. Further studies have been made of the physical properties of hen's apovitellenin I, the principal low-molecular-weight protein from the high-lipid low density lipoprotein of the yolk of hen's eggs. The methods used included chromatography, sedimentation, viscosity, optical rotation, and spin labelling; the solvents used were aqueous urea, and, for some experiments, aqueous formamide. It is concluded that a neutral pH the protein is present in these solvents as an aggregate of molecular weight 36000 corresponding to a tetramer. Below about pH 4-5 solutions of the tetramer increased greatly in viscosity; furthermore, a covalently bound spin label increased in mobility. These changes were reversible and were apparently the result of dissociation of the tetramer to a dimer. This disociation did not involve a change in the proportion of alpha-helix. In contrast to the results of previous experiments, it now seems probably that the apovitellenin I dimer is stabilized by an interchain disulphide bond."}
{"id": "PMID:14611", "title": "Biochemical differences between alcohol dehydrogenases of Drosophila melanogaster.", "content": "This paper describes substrate specificities, developmental changes in activity, pH profiles, and heat stabilities of isozymes produced by four Adh genotypes in D. melanogaster. No differences are found in the substrate specificities of isozymes from the different genotypes but studies of the other three properties reveal significant differences between the isozymes. Thus relatively low activities are found among extracts of AdhF Adhn2 larvae and among extracts of AdhF AdhF adults aged 44 days. Also AdhF AdhS and AdhS AdhS extracts have relatively high activities at pH 6-5, and AdhF Adhn2 extracts have relatively low activities at pH values above 10-0. Finally, extracts of AdhF AdhF and AdhF AdhS are more stable at 40 degrees C than are those of AdhS AdhS and AdhF Adhn2.", "contents": "Biochemical differences between alcohol dehydrogenases of Drosophila melanogaster. This paper describes substrate specificities, developmental changes in activity, pH profiles, and heat stabilities of isozymes produced by four Adh genotypes in D. melanogaster. No differences are found in the substrate specificities of isozymes from the different genotypes but studies of the other three properties reveal significant differences between the isozymes. Thus relatively low activities are found among extracts of AdhF Adhn2 larvae and among extracts of AdhF AdhF adults aged 44 days. Also AdhF AdhS and AdhS AdhS extracts have relatively high activities at pH 6-5, and AdhF Adhn2 extracts have relatively low activities at pH values above 10-0. Finally, extracts of AdhF AdhF and AdhF AdhS are more stable at 40 degrees C than are those of AdhS AdhS and AdhF Adhn2."}
{"id": "PMID:14612", "title": "Ord River arboviruses--the study site and mosquitoes.", "content": "The Ord Valey of tropical Western Australia has been studied for arbovirus activity following the development of a man-made lake of considerable size, a diversion dam and an irrigation scheme. Kununurra, the largest town in the valley, is the focus for very large populations of  birds and mosquitoes. The irrigation areas have not been important as mosquito breeding areas because of the excessive use of insecticides. Lake Argyle does not support high mosquito a bird population at present. However, this may change as the ecosystem stabilizes. The mosquito fauna of the Ord Valley is dominated by Culex annulirostris.", "contents": "Ord River arboviruses--the study site and mosquitoes. The Ord Valey of tropical Western Australia has been studied for arbovirus activity following the development of a man-made lake of considerable size, a diversion dam and an irrigation scheme. Kununurra, the largest town in the valley, is the focus for very large populations of  birds and mosquitoes. The irrigation areas have not been important as mosquito breeding areas because of the excessive use of insecticides. Lake Argyle does not support high mosquito a bird population at present. However, this may change as the ecosystem stabilizes. The mosquito fauna of the Ord Valley is dominated by Culex annulirostris."}
{"id": "PMID:14613", "title": "Ord River arboviruses--isolations from mosquitoes.", "content": "One hundred and thirty presumptive viruses have been isolated from 485 pools made from 23,872 mosquitoes collected in the Ord River area of North-West Australia. One hundred and eleven of the virus isolates isolates came from pools of Culex annulirostis, the dominant mosquito species caught in the vicinity of Kununurra. Forty-five of the viruses pathogenic for newborn mice have been further characterized-19 as Flaviviruses, 1 Alphavirus, 9 Koongol, 1 Mapputta and 15 non-haemagglutinating viruses of which 6 are Corripata. Thirty-seven isolates were from Culex annulirostis, 7 from Aedomyia catasticta and 1 from aedes tremulus. All Corriparta isolates were from Aedomyia catasticta. The Flaviviruses comprised 13 Kunjin and 6 MVE isolates.", "contents": "Ord River arboviruses--isolations from mosquitoes. One hundred and thirty presumptive viruses have been isolated from 485 pools made from 23,872 mosquitoes collected in the Ord River area of North-West Australia. One hundred and eleven of the virus isolates isolates came from pools of Culex annulirostis, the dominant mosquito species caught in the vicinity of Kununurra. Forty-five of the viruses pathogenic for newborn mice have been further characterized-19 as Flaviviruses, 1 Alphavirus, 9 Koongol, 1 Mapputta and 15 non-haemagglutinating viruses of which 6 are Corripata. Thirty-seven isolates were from Culex annulirostis, 7 from Aedomyia catasticta and 1 from aedes tremulus. All Corriparta isolates were from Aedomyia catasticta. The Flaviviruses comprised 13 Kunjin and 6 MVE isolates."}
{"id": "PMID:14614", "title": "Essential hypertension--the starting point for improved drug treatment.", "content": "Hypertension is a common disease and plays an important role as a potentially remediable contributor to cardiovascular causes of death in the community. In moderate to severe hypertension recent treatment has improved morbidity and mortality substantially, but it is disappointing that despite this myocardial infarction still stands as an important cause of death. In this regard it is encouraging that beta adrenergic blockade may be useful not only in lowering blood pressure, but also possibly in reducing independently the risk of myocardial infarction and/or sudden death in some patients. In mild hypertension the number of patients is large and the possible beneficial effect of treatment less well-established, so that there is a clear need for further research in order to define patients at relatively high risk in this group.", "contents": "Essential hypertension--the starting point for improved drug treatment. Hypertension is a common disease and plays an important role as a potentially remediable contributor to cardiovascular causes of death in the community. In moderate to severe hypertension recent treatment has improved morbidity and mortality substantially, but it is disappointing that despite this myocardial infarction still stands as an important cause of death. In this regard it is encouraging that beta adrenergic blockade may be useful not only in lowering blood pressure, but also possibly in reducing independently the risk of myocardial infarction and/or sudden death in some patients. In mild hypertension the number of patients is large and the possible beneficial effect of treatment less well-established, so that there is a clear need for further research in order to define patients at relatively high risk in this group."}
{"id": "PMID:14616", "title": "Pharmacodynamic studies on the antihypertensive effectiveness of beta-blocking drugs.", "content": "Beta-adrenoceptor antagonists are effective antihypertensive agents in the majority of patients with uncomplicated essential hypertension. Their antipressor activity is greater on systolic than diastolic pressure and greatest during dynamic exertion. Their circulatory effects are maximum within 1-2 hours of ingestion and the antipressor effects of a single dose are detectable for over eight hours. Both the immediate and long-term blood pressure lowering effects of these drugs are dose-related. The reduction in exercise systolic pressure is related to the logarithm of the dose of each drug; the reductions in pressure at rest follow no simple mathematical function. There is wide individual variation in the plasma concentrations achieved after a given oral dose, although the averaged values follow a linear regression. There are wide discrepancies between plasma-concentration profile and magnitude and duration of antihypertensive activity; blood pressure lowering activity persists for significantly longer than the drug is detectable in plasma. The antihypertensive effects of the beta-blocking drugs are enhanced during chronic administration without habituation. Their effects are specific but independent of the immediate presence of the drug, i.e. blood pressure lowering activity persists after clearance of the drug from the body. The ancillary pharmacological properties of these drugs neither augment nor detract from their antihypertensive potency, although the possession of intrinsic vasodilator activity enhances reduction in the blood pressure standing at rest. Beta-blocking drugs add a new dimension to antihypertensive treatment in their specific potential to reduce the coronary consequences of the disease.", "contents": "Pharmacodynamic studies on the antihypertensive effectiveness of beta-blocking drugs. Beta-adrenoceptor antagonists are effective antihypertensive agents in the majority of patients with uncomplicated essential hypertension. Their antipressor activity is greater on systolic than diastolic pressure and greatest during dynamic exertion. Their circulatory effects are maximum within 1-2 hours of ingestion and the antipressor effects of a single dose are detectable for over eight hours. Both the immediate and long-term blood pressure lowering effects of these drugs are dose-related. The reduction in exercise systolic pressure is related to the logarithm of the dose of each drug; the reductions in pressure at rest follow no simple mathematical function. There is wide individual variation in the plasma concentrations achieved after a given oral dose, although the averaged values follow a linear regression. There are wide discrepancies between plasma-concentration profile and magnitude and duration of antihypertensive activity; blood pressure lowering activity persists for significantly longer than the drug is detectable in plasma. The antihypertensive effects of the beta-blocking drugs are enhanced during chronic administration without habituation. Their effects are specific but independent of the immediate presence of the drug, i.e. blood pressure lowering activity persists after clearance of the drug from the body. The ancillary pharmacological properties of these drugs neither augment nor detract from their antihypertensive potency, although the possession of intrinsic vasodilator activity enhances reduction in the blood pressure standing at rest. Beta-blocking drugs add a new dimension to antihypertensive treatment in their specific potential to reduce the coronary consequences of the disease."}
{"id": "PMID:14617", "title": "Blood pressure variability in patients on beta-blockers.", "content": "The direct arterial blood pressure was monitored over 24 hours in unrestricted untreated patients in order to obtain the average pressure and standard deviation over 24 hours. The standard deviation was taken as the index of variability of pressure. In eight subjects the study was repeated three months after commencement of treatment with a beta-adrenergic blocking agent (tolamolol, 300 mg/day). In these subjects tolamolol resulted in a fall in mean blood pressure from 107 to 92 mmHg (P less than 0-05) and a fall in heart rate from 82 to 70 beats per minute (P less than 0-01). The variability in blood pressure, however, was unaffected by treatment.", "contents": "Blood pressure variability in patients on beta-blockers. The direct arterial blood pressure was monitored over 24 hours in unrestricted untreated patients in order to obtain the average pressure and standard deviation over 24 hours. The standard deviation was taken as the index of variability of pressure. In eight subjects the study was repeated three months after commencement of treatment with a beta-adrenergic blocking agent (tolamolol, 300 mg/day). In these subjects tolamolol resulted in a fall in mean blood pressure from 107 to 92 mmHg (P less than 0-05) and a fall in heart rate from 82 to 70 beats per minute (P less than 0-01). The variability in blood pressure, however, was unaffected by treatment."}
{"id": "PMID:14622", "title": "A beta-blocker-based antihypertensive drug program guided by age and renin.", "content": "From analyses of the effectiveness of beta-blocker monotherapy in relation to the patient's age and to pre-treatment renin determinations an antihypertensive drug program is proposed in which beta-blockers form the cornerstone. Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%), or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall into two categories: younger patients with fairly mild hypertension and older pateients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of beta-blocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, beta-blockers normalized blood pressure (larger than or equal to 95 mmHg diastolic) in three-quarters of the younger than 40-year-olds, in about half of those aged 40--60 years, but in only 20% of those aged over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state while those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the beta-blockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, though not exclusively, to renin suppression.", "contents": "A beta-blocker-based antihypertensive drug program guided by age and renin. From analyses of the effectiveness of beta-blocker monotherapy in relation to the patient's age and to pre-treatment renin determinations an antihypertensive drug program is proposed in which beta-blockers form the cornerstone. Patients with essential hypertension can be subdivided into groups with low (19%), normal (59%), or high (23%) renin sodium index. The proportion with low renin hypertension increases with age. Patients with high renin fall into two categories: younger patients with fairly mild hypertension and older pateients with more severe hypertension and signs of renal disease. The antihypertensive efficacy of beta-blocker monotherapy is best in high renin forms, good but less consistent in normal renin patients and uniformly bad in low renin hypertensives. In relation to age, beta-blockers normalized blood pressure (larger than or equal to 95 mmHg diastolic) in three-quarters of the younger than 40-year-olds, in about half of those aged 40--60 years, but in only 20% of those aged over 60 years. On this basis, it is postulated that the older patients with a low renin exhibit a relatively hypoadrenergic state while those with a normal or high renin--for a given age and elevated pressure--have a relatively increased adrenergic nervous activity. Because the beta-blockers have a potent suppressive action on the renin-angiotensin system--and, as a consequence, on angiotensin vasoconstriction, aldosterone volume expansion and central stimulatory feedback mechanisms--their antihypertensive mode of action may be linked to an important extent, though not exclusively, to renin suppression."}
{"id": "PMID:14623", "title": "The pharmacokinetic characteristics of beta-receptor antagonists in man--similarities and differences of clinical relevance.", "content": "The aliphatic partial structure common to the beta-receptor antagonists leads to similar products of their biotransformation. The main qualitative and quantitative differences of the metabolism of the compounds of this class, however, rest in the nature of their aromatic or heterocyclic substituents. The physico-chemical properties of the beta-blockers appear to be predominantly responsible for the extent of metabolic degradation and for the distribution in the body, especially for the binding to proteins. As a consequence of their different biological disposition the clinically relevant systemic bioavailabilities of the various beta-blockers from oral doses differ drastically. Practolol maintains an extreme position among all other compounds: It is most hydrophilic, it is not bound to proteins, it is metabolized least, but cleared renally in unchanged form to 85% of the dose. Despite its extremely high systemic bioavailability, relatively high daily doses were required for therapy. The receptor sensitivity for practolol has been rated 2 to 3 powers of 1- lower than of propranolol. Comparative pharmacokinetic assessment of beta-receptor antagonists requires quantitative analytical data in clinically representative groups of patients. This has been demonstrated by respective studies with oxprenolol. The intra- and inter-individual systemic bioavailability, the differential analysis of plasma and erythrocytes, the multiexponential elimination kinetics, and their possible dependence on the dose have been studied as clinically relevant pharmacokinetic characteristics. The continuing attempt of the pharmaceutical industry to optimize the properties of beta-blockers also has taken advantage of the slow release principle in oral dosage forms as shown by the example of oxprenolol. The beta-receptor antagonists belong to one of the youngest classes of pharmaceuticals. Pharmacokinetic and metabolic data for the different representatives of this class have been generated in different laboratories with different approaches and different techniques. Therefore, full comparative documentation is still incomplete.", "contents": "The pharmacokinetic characteristics of beta-receptor antagonists in man--similarities and differences of clinical relevance. The aliphatic partial structure common to the beta-receptor antagonists leads to similar products of their biotransformation. The main qualitative and quantitative differences of the metabolism of the compounds of this class, however, rest in the nature of their aromatic or heterocyclic substituents. The physico-chemical properties of the beta-blockers appear to be predominantly responsible for the extent of metabolic degradation and for the distribution in the body, especially for the binding to proteins. As a consequence of their different biological disposition the clinically relevant systemic bioavailabilities of the various beta-blockers from oral doses differ drastically. Practolol maintains an extreme position among all other compounds: It is most hydrophilic, it is not bound to proteins, it is metabolized least, but cleared renally in unchanged form to 85% of the dose. Despite its extremely high systemic bioavailability, relatively high daily doses were required for therapy. The receptor sensitivity for practolol has been rated 2 to 3 powers of 1- lower than of propranolol. Comparative pharmacokinetic assessment of beta-receptor antagonists requires quantitative analytical data in clinically representative groups of patients. This has been demonstrated by respective studies with oxprenolol. The intra- and inter-individual systemic bioavailability, the differential analysis of plasma and erythrocytes, the multiexponential elimination kinetics, and their possible dependence on the dose have been studied as clinically relevant pharmacokinetic characteristics. The continuing attempt of the pharmaceutical industry to optimize the properties of beta-blockers also has taken advantage of the slow release principle in oral dosage forms as shown by the example of oxprenolol. The beta-receptor antagonists belong to one of the youngest classes of pharmaceuticals. Pharmacokinetic and metabolic data for the different representatives of this class have been generated in different laboratories with different approaches and different techniques. Therefore, full comparative documentation is still incomplete."}
{"id": "PMID:14625", "title": "The vasodilator--beta-blocker interaction--some determinants of its clinical success.", "content": "A number of structurally dissimilar compounds, sharing the ability to induce vasodilatation have come into clinical usefulness as antihypertensive drugs. Their successful utilisation often depends critically on an appropriate combination with diuretics and beta-blockers. Beta-blockers can specifically inhibit the reflex cardiac stimulation which otherwise may limit the tolerability and haemodynamic value of these drugs. A synergistic antihypertensive effect has been demonstrated with hydrallazine and propranolol and possibly exists with other combinations. Generally, vasodilators are not first-line drugs in chronic therapy but are best added to beta-blockers. Variations of the dose-response and the time-course of effect are stressed as being important determinants of a successful interaction.", "contents": "The vasodilator--beta-blocker interaction--some determinants of its clinical success. A number of structurally dissimilar compounds, sharing the ability to induce vasodilatation have come into clinical usefulness as antihypertensive drugs. Their successful utilisation often depends critically on an appropriate combination with diuretics and beta-blockers. Beta-blockers can specifically inhibit the reflex cardiac stimulation which otherwise may limit the tolerability and haemodynamic value of these drugs. A synergistic antihypertensive effect has been demonstrated with hydrallazine and propranolol and possibly exists with other combinations. Generally, vasodilators are not first-line drugs in chronic therapy but are best added to beta-blockers. Variations of the dose-response and the time-course of effect are stressed as being important determinants of a successful interaction."}
{"id": "PMID:14626", "title": "Additive effect of beta-adrenergic blockers in combination with vasodilators in lowering blood pressure.", "content": "Complications of hypertension are by far the greatese preventable public health problem in many of the developed countries of the world. Pharmacologic interventions which primarily involve drug interactions are the generally available and effective means of preventing or delaying these hypertensive complications. Mechanisms of beneficial antihypertensive drug interactions involve simultaneous reduction or control of blood volume (diuretic agents) and decrease of peripheral resistance. Reduction of peripheral resistance without producing intolerable side effects has recetnly been achieved by a complex drug interaction. This interaction involves simultaneous vasodilation and inhibition by beta-adrenergic blocking agents of reflex activation of the renin-angiotensin axis. Clonidine, by effects similar to propranolol, can substitute for propranolol in some patients, or add to the beneficial effects of this important drug interaction.", "contents": "Additive effect of beta-adrenergic blockers in combination with vasodilators in lowering blood pressure. Complications of hypertension are by far the greatese preventable public health problem in many of the developed countries of the world. Pharmacologic interventions which primarily involve drug interactions are the generally available and effective means of preventing or delaying these hypertensive complications. Mechanisms of beneficial antihypertensive drug interactions involve simultaneous reduction or control of blood volume (diuretic agents) and decrease of peripheral resistance. Reduction of peripheral resistance without producing intolerable side effects has recetnly been achieved by a complex drug interaction. This interaction involves simultaneous vasodilation and inhibition by beta-adrenergic blocking agents of reflex activation of the renin-angiotensin axis. Clonidine, by effects similar to propranolol, can substitute for propranolol in some patients, or add to the beneficial effects of this important drug interaction."}
{"id": "PMID:14627", "title": "Labetalol (AH5158), a competitive alpha- and beta-receptor blocking drug, in the management of hypertension.", "content": "The effects of intravenous labetalol, a drug with both alpha- and beta-adrenergic receptor blocking actions, have been studied in 20 severely hypertensive patients. There was a prompt and sustained fall in arterial pressure; severe hypotension did not occur in recumbent patients but postural hypotension was common. Pulse rate was consistently reduced, but bradycardia was not a problem. Significant and correlated falls in plasma angiotensin II and aldosterone were seen. In a direct comparison with intravenous propranolol, labetalol was less effective in lowering plasma angiotensin II, but more effective in reducing blood pressure. Oral labetalol provided good control of blood pressure and other features in two patients with phaeochromocytoma. Intravenous labetalol was similarly effective in controlling a hypertensive crisis following clonidine withdrawal.", "contents": "Labetalol (AH5158), a competitive alpha- and beta-receptor blocking drug, in the management of hypertension. The effects of intravenous labetalol, a drug with both alpha- and beta-adrenergic receptor blocking actions, have been studied in 20 severely hypertensive patients. There was a prompt and sustained fall in arterial pressure; severe hypotension did not occur in recumbent patients but postural hypotension was common. Pulse rate was consistently reduced, but bradycardia was not a problem. Significant and correlated falls in plasma angiotensin II and aldosterone were seen. In a direct comparison with intravenous propranolol, labetalol was less effective in lowering plasma angiotensin II, but more effective in reducing blood pressure. Oral labetalol provided good control of blood pressure and other features in two patients with phaeochromocytoma. Intravenous labetalol was similarly effective in controlling a hypertensive crisis following clonidine withdrawal."}
{"id": "PMID:14630", "title": "A comprehensive behaviour modification programme for the treatment of anorexia nervosa: results in six cases.", "content": "Behavioural analysis and psychodynamic hypotheses were used to develop a comprehensive behaviour modification programme for the treatment of primary anorexia nervosa. This was applied to six female patients and the results obtained are reported.", "contents": "A comprehensive behaviour modification programme for the treatment of anorexia nervosa: results in six cases. Behavioural analysis and psychodynamic hypotheses were used to develop a comprehensive behaviour modification programme for the treatment of primary anorexia nervosa. This was applied to six female patients and the results obtained are reported."}
{"id": "PMID:14645", "title": "The relationship between chemical structure and basicity in some morpholine compounds.", "content": "The influence of various substituents upon the pKa values of a series of 2-phenylmorpholines is discussed. The results are interpreted in terms of the preferred conformations of the morpholine ring and the inductive effect of the various substituents. The lack of analgesic activity in these compounds could be attributed to their low pKa.", "contents": "The relationship between chemical structure and basicity in some morpholine compounds. The influence of various substituents upon the pKa values of a series of 2-phenylmorpholines is discussed. The results are interpreted in terms of the preferred conformations of the morpholine ring and the inductive effect of the various substituents. The lack of analgesic activity in these compounds could be attributed to their low pKa."}
{"id": "PMID:14646", "title": "Hysteresis at an electrochemical membrane model and its possible role in circulation research.", "content": "On an artificial electrochemical membrane, properties of hysteresis are demonstrated by cyclic variation of pH. The properties are decreased by cAMP, theophylline, cysteine, heparin and increased by ADP.", "contents": "Hysteresis at an electrochemical membrane model and its possible role in circulation research. On an artificial electrochemical membrane, properties of hysteresis are demonstrated by cyclic variation of pH. The properties are decreased by cAMP, theophylline, cysteine, heparin and increased by ADP."}
{"id": "PMID:14647", "title": "Physiological antagonism between PGE2, PGA1, PGF1-alpha and NADP, beta-NAD on isolated rabbit jejunum.", "content": "The antagonistic action between the prostaglandins PGE2, PGA1 and PGF1-alpha, on the one hand, and nicotinamide-adenine-dinucleotide-phosphate (NADP or TPN) and beta-nicotinamide-adenine-dinucleotide (beta-NAD or DPN) on the other, were experimentally studied on rabbit isolated jejunum. Our results support our previously expressed hypothesis that in the living organism there exist regulatory systems to control the actions of extremely potent substances such as the PGs. NADP and beta-NAD may therefore be grouped together with AMP, ADP and ATP as naturally occurring compounds that antagonise the actions of PGs.", "contents": "Physiological antagonism between PGE2, PGA1, PGF1-alpha and NADP, beta-NAD on isolated rabbit jejunum. The antagonistic action between the prostaglandins PGE2, PGA1 and PGF1-alpha, on the one hand, and nicotinamide-adenine-dinucleotide-phosphate (NADP or TPN) and beta-nicotinamide-adenine-dinucleotide (beta-NAD or DPN) on the other, were experimentally studied on rabbit isolated jejunum. Our results support our previously expressed hypothesis that in the living organism there exist regulatory systems to control the actions of extremely potent substances such as the PGs. NADP and beta-NAD may therefore be grouped together with AMP, ADP and ATP as naturally occurring compounds that antagonise the actions of PGs."}
{"id": "PMID:14648", "title": "An experimental and clinical pharmacological study of the influence of triamterene on the diuretic and saluretic properties of furosemide xantinol.", "content": "The diuretic and saluretic effect of furosemide xantinol administered alone and mixed with different amounts of 2,4,7-triamino-6-phenylpteridine (triamterene) have been investigated in rat and man. The presence of triamterene resulted in a dose dependent inhibition of furosemide xantinol induced diuresis in both species. It was necessary to reduce the amount of triamterene present in the mixture to approximately half that of the one theoretically required according to considerations of the recommended therapeutic doses of the two diuretics before significant inhibition was avoided. Nevertheless, this reduced amount of triamterene proved sufficient to inhibit the distal tubular exchange of Na+ for K+ and H+ and a mixture formulated to give the ratio of 40 mg furosemide xantinol (as base) plus 25 mg triamterene (Salidur) was shown to produce a smooth but efficient loss of water and Na+ in the absence of detectable kaliuresis or reduction in urinary pH, thereby reducing the usual risk of inducing hypokalaemic alkalosis.", "contents": "An experimental and clinical pharmacological study of the influence of triamterene on the diuretic and saluretic properties of furosemide xantinol. The diuretic and saluretic effect of furosemide xantinol administered alone and mixed with different amounts of 2,4,7-triamino-6-phenylpteridine (triamterene) have been investigated in rat and man. The presence of triamterene resulted in a dose dependent inhibition of furosemide xantinol induced diuresis in both species. It was necessary to reduce the amount of triamterene present in the mixture to approximately half that of the one theoretically required according to considerations of the recommended therapeutic doses of the two diuretics before significant inhibition was avoided. Nevertheless, this reduced amount of triamterene proved sufficient to inhibit the distal tubular exchange of Na+ for K+ and H+ and a mixture formulated to give the ratio of 40 mg furosemide xantinol (as base) plus 25 mg triamterene (Salidur) was shown to produce a smooth but efficient loss of water and Na+ in the absence of detectable kaliuresis or reduction in urinary pH, thereby reducing the usual risk of inducing hypokalaemic alkalosis."}
{"id": "PMID:14649", "title": "Inhibitory effect of beta-adrenergic stimulants on the histamine reaction in human skin. I. Studies with fenoterol.", "content": "In 20 volunteers histamine inhibition by fenoterol (Th 1165 a) was studied. The wheal and erythema reaction caused by intracutaneous application of 5 mug histamine can be inhibited by applying fenoterol in doses from 100--400 mug in form of a metered aerosol on the skin 5 min before the injection of histamine. In this study the dose-reaction effect yielded on ED50 of 140 mug fenoterol.", "contents": "Inhibitory effect of beta-adrenergic stimulants on the histamine reaction in human skin. I. Studies with fenoterol. In 20 volunteers histamine inhibition by fenoterol (Th 1165 a) was studied. The wheal and erythema reaction caused by intracutaneous application of 5 mug histamine can be inhibited by applying fenoterol in doses from 100--400 mug in form of a metered aerosol on the skin 5 min before the injection of histamine. In this study the dose-reaction effect yielded on ED50 of 140 mug fenoterol."}
{"id": "PMID:14651", "title": "[Double-blind clinical study of carpipramine/placebo (author's transl)].", "content": "A statistically planned double blind cross-over test with the substances 1-[3-(10,11-dihydro-5H-dibenz[b;f]-azepin-5-yl)-propyl]-4-piperidino-piperidine-4-carboxamide dihydrochloride-monohydrate (carpipramine, BAY b 4343 b) and placebo (BAY b 4343 a) was carried out on 30 long-term hospitalized schizophrenic patients. The study was evaluated by means of the kappa2-test and yielded the following results: 1. It could be statistically proved that carpipramine has a positive effect on psycho-pathological disorders in the behaviour of long-term hospitalized schizophrenic patients (kappa2 = 9.224; FG = 1; p greater than 0.05). 2. As regards the favourable influence of carpipramine on \"productive\" versus \"non-productive\" form of schizophrenia there were no differences. 3. Side effects or complications of a psychic, autonomic and/or motoric manner could not be seen. The usual laboratory tests showed no deviation from normal.", "contents": "[Double-blind clinical study of carpipramine/placebo (author's transl)]. A statistically planned double blind cross-over test with the substances 1-[3-(10,11-dihydro-5H-dibenz[b;f]-azepin-5-yl)-propyl]-4-piperidino-piperidine-4-carboxamide dihydrochloride-monohydrate (carpipramine, BAY b 4343 b) and placebo (BAY b 4343 a) was carried out on 30 long-term hospitalized schizophrenic patients. The study was evaluated by means of the kappa2-test and yielded the following results: 1. It could be statistically proved that carpipramine has a positive effect on psycho-pathological disorders in the behaviour of long-term hospitalized schizophrenic patients (kappa2 = 9.224; FG = 1; p greater than 0.05). 2. As regards the favourable influence of carpipramine on \"productive\" versus \"non-productive\" form of schizophrenia there were no differences. 3. Side effects or complications of a psychic, autonomic and/or motoric manner could not be seen. The usual laboratory tests showed no deviation from normal."}
{"id": "PMID:14652", "title": "[Activity profile of carpipramine. Results of an open trial and a double-blind trial versus doxepin].", "content": "During an uncontrolled trial 46 depressed patients (39 endogenous depressions, 5 schizoaffective psychoses and 2 paranoic schizophrenics with depressive syndromes) were treated for 43 days on the average with 3 X 100 mg 1-[3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-propyl]-4-piperidino-piperidine-4-carboxamide-dihydrochloride-monohydrate (carpipramine) daily. The clinical impression of the improvement and the results of the Hamilton-Scale for depressions (19 patients, 24 items) showed a clear antidepressive effect of carpipramine. During a double-blind trial 14 patients were treated with carpipramine and 16 with doxepine for 30 days. Most patients suffered from endogenous depressions with paranoic symptoms or from schizophrenia with depressive syndromes. Statistical analysis of the Hamilton-Scale for depressions and the AMP-System showed the antidepressive and antipsychotic effect of carpipramine. Analysis of covariance showed no significant difference between carpipramine and doxepine. Altogether we treated 60 depressive patients with carpipramine. 26 patients improved very well and 11 moderately, that means 37 patients out of 60 reacted positively to therapy with carpipramine. One endogenous depression and a schizoaffective psychosis changed into a manic phase. A provocation of schizophrenic symptoms was not noticed. Carpipramine was very well tolerated and can be classified as a non-sedative antidepressant with an antipsychotic effect.", "contents": "[Activity profile of carpipramine. Results of an open trial and a double-blind trial versus doxepin]. During an uncontrolled trial 46 depressed patients (39 endogenous depressions, 5 schizoaffective psychoses and 2 paranoic schizophrenics with depressive syndromes) were treated for 43 days on the average with 3 X 100 mg 1-[3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-propyl]-4-piperidino-piperidine-4-carboxamide-dihydrochloride-monohydrate (carpipramine) daily. The clinical impression of the improvement and the results of the Hamilton-Scale for depressions (19 patients, 24 items) showed a clear antidepressive effect of carpipramine. During a double-blind trial 14 patients were treated with carpipramine and 16 with doxepine for 30 days. Most patients suffered from endogenous depressions with paranoic symptoms or from schizophrenia with depressive syndromes. Statistical analysis of the Hamilton-Scale for depressions and the AMP-System showed the antidepressive and antipsychotic effect of carpipramine. Analysis of covariance showed no significant difference between carpipramine and doxepine. Altogether we treated 60 depressive patients with carpipramine. 26 patients improved very well and 11 moderately, that means 37 patients out of 60 reacted positively to therapy with carpipramine. One endogenous depression and a schizoaffective psychosis changed into a manic phase. A provocation of schizophrenic symptoms was not noticed. Carpipramine was very well tolerated and can be classified as a non-sedative antidepressant with an antipsychotic effect."}
{"id": "PMID:14656", "title": "Lack of beta-adrenergic activity of isoflurane in the dog: a comparison of circulatory effects of halothane and isoflurane after propranolol administration.", "content": "The studies were undertaken to determine whether isoflurance inhalation is associated with a degree of beta-adrenergic action that is potentially important in clinical situations, and to compare the circulatory tolerance to isoflurane and halothane in dogs following beta blockade. We measured arterial and pulmonary artery pressure, left and right ventricular filling pressure, heart rate and cardiac output, and derived stroke volume and systemic and pulmonary vascular resistances in 13 mongrel dogs. The haemodynamic response to 1 MAC and 2 MAC isoflurane was studied in seven dogs and was similar before and after propranolol 0.1mg/kg i.v. In six dogs, propranolol 0.5mg/kg caused no significant changes in the circulatory response to 1 MAC and 2 MAC isoflurane or 1 MAC halothane. However, in three dogs, administration of 2 MAC halothane after propranolol 0.5mg/kg resulted in such profound circulatory depression as to preclude further study. These data suggest that (a) isoflurane possesses no clinically important beta-adrenergic stimulating activity; (b) there is no adverse drug interaction upon the circulation with the combination of isoflurane and propranolol; (c) in the presence of moderated profound beta-adrenergic blockade, 2 MAC isoflurane may be tolerated better than 2 MAC halothane.", "contents": "Lack of beta-adrenergic activity of isoflurane in the dog: a comparison of circulatory effects of halothane and isoflurane after propranolol administration. The studies were undertaken to determine whether isoflurance inhalation is associated with a degree of beta-adrenergic action that is potentially important in clinical situations, and to compare the circulatory tolerance to isoflurane and halothane in dogs following beta blockade. We measured arterial and pulmonary artery pressure, left and right ventricular filling pressure, heart rate and cardiac output, and derived stroke volume and systemic and pulmonary vascular resistances in 13 mongrel dogs. The haemodynamic response to 1 MAC and 2 MAC isoflurane was studied in seven dogs and was similar before and after propranolol 0.1mg/kg i.v. In six dogs, propranolol 0.5mg/kg caused no significant changes in the circulatory response to 1 MAC and 2 MAC isoflurane or 1 MAC halothane. However, in three dogs, administration of 2 MAC halothane after propranolol 0.5mg/kg resulted in such profound circulatory depression as to preclude further study. These data suggest that (a) isoflurane possesses no clinically important beta-adrenergic stimulating activity; (b) there is no adverse drug interaction upon the circulation with the combination of isoflurane and propranolol; (c) in the presence of moderated profound beta-adrenergic blockade, 2 MAC isoflurane may be tolerated better than 2 MAC halothane."}
{"id": "PMID:14657", "title": "An evaluation of the AVL 937C blood-gas and pH microanalyser.", "content": "The AVL 937C blood-gas and pH microanalyser was evaluated with particular reference to its use in obsterics and in neonatal paediatrics in which its ability to analyse blood smaples as small as 40 micronlitre would be of particular value. Analysing samples of cord blood, maternal venous blood and foetal scalp blood, the reproducibility over the range of values measured was excellent with samples of 40-100 micronlitre. SD of the variation in values measured on samples collected in syringes were po2 0.11 kPa; Pco2 0.21 kPa; PH 0.005 unit. The same values for specimens collected in capillary tubes were: Po2 0.19 kPa;Pco 0.43 kPa; pH 0.013 unit. Analysis of tonometered blood samples showed a similar high standard of accuracy. The 91-98% confidence limits for the measurement of blood-gas values in samples collected in syringes were: Po2-0.22 to +0.49kPa; Pco2-0.53 to +0.42 kPa. The same values for samples collected in capillary tubes were: Po2 -0.38 to +0.70 kPa; Pco2 -0.97 to +0.86 kPa.", "contents": "An evaluation of the AVL 937C blood-gas and pH microanalyser. The AVL 937C blood-gas and pH microanalyser was evaluated with particular reference to its use in obsterics and in neonatal paediatrics in which its ability to analyse blood smaples as small as 40 micronlitre would be of particular value. Analysing samples of cord blood, maternal venous blood and foetal scalp blood, the reproducibility over the range of values measured was excellent with samples of 40-100 micronlitre. SD of the variation in values measured on samples collected in syringes were po2 0.11 kPa; Pco2 0.21 kPa; PH 0.005 unit. The same values for specimens collected in capillary tubes were: Po2 0.19 kPa;Pco 0.43 kPa; pH 0.013 unit. Analysis of tonometered blood samples showed a similar high standard of accuracy. The 91-98% confidence limits for the measurement of blood-gas values in samples collected in syringes were: Po2-0.22 to +0.49kPa; Pco2-0.53 to +0.42 kPa. The same values for samples collected in capillary tubes were: Po2 -0.38 to +0.70 kPa; Pco2 -0.97 to +0.86 kPa."}
{"id": "PMID:14658", "title": "Relative amnesic actions of diazepam, flunitrazepam and lorazepam in man.", "content": "1. Ten postcards were shown to groups of ten to twenty patients over 60, 90 or 270 min after intravenous injection of saline, diazepam (10 and 20 mg), flunitrazepam (1 and 2 mg) and lorazepam (4 mg). 2. Incidence of amnesia was estimated by the patients' ability to recall or recognize these cards and to recall various other incidents in the para-anaesthetic period. 3. The use of a dummy confirmed the reliability of the method of testing for amnesia in man. 4. Flunitrazepam produced a dose-related incidence of amnesia slightly longer than with the equivalent (1 x 10) dose of diazepam. 5. The onset of amnesia was slower with lorazepam (4 mg) but appeared to last for up to four hours. 6. This amnesic action of lorazepam was paralleled by a useful sensitive effect but there was no similar correlation for diazepam and flunitrazepam. 7. With three drugs of different duration of action it should be possible to produce amnesia for any required clinical situation.", "contents": "Relative amnesic actions of diazepam, flunitrazepam and lorazepam in man. 1. Ten postcards were shown to groups of ten to twenty patients over 60, 90 or 270 min after intravenous injection of saline, diazepam (10 and 20 mg), flunitrazepam (1 and 2 mg) and lorazepam (4 mg). 2. Incidence of amnesia was estimated by the patients' ability to recall or recognize these cards and to recall various other incidents in the para-anaesthetic period. 3. The use of a dummy confirmed the reliability of the method of testing for amnesia in man. 4. Flunitrazepam produced a dose-related incidence of amnesia slightly longer than with the equivalent (1 x 10) dose of diazepam. 5. The onset of amnesia was slower with lorazepam (4 mg) but appeared to last for up to four hours. 6. This amnesic action of lorazepam was paralleled by a useful sensitive effect but there was no similar correlation for diazepam and flunitrazepam. 7. With three drugs of different duration of action it should be possible to produce amnesia for any required clinical situation."}
{"id": "PMID:14659", "title": "Plasma concentrations of benzodiazepines.", "content": "1. Twenty anxious patients were treated with medazepam, diazepam, chlordiazepoxide, amylobarbitone and placebo, each given in flexible dosage for 2-4 weeks. 2. At the end of each treatment, a series of clinical, physiological and behavioural variables were measured and plasma samples were taken for estimation of the appropriate drug and metabolite concentrations. 3. Nordiazepam was shown to be an important metabolite of both medazepam and diazepam: the ratio of medazepam to noradiazepam was 0.14 and the ratio of diazepam to nordiazepam following diazepam administration was 0.72. 4. No significant correlations were found between the plasma concentrations of any of the treatments and the clinical ratings or behavioural measures. 5. Some relationship was shown between levels of medazepam and its physiological effects.", "contents": "Plasma concentrations of benzodiazepines. 1. Twenty anxious patients were treated with medazepam, diazepam, chlordiazepoxide, amylobarbitone and placebo, each given in flexible dosage for 2-4 weeks. 2. At the end of each treatment, a series of clinical, physiological and behavioural variables were measured and plasma samples were taken for estimation of the appropriate drug and metabolite concentrations. 3. Nordiazepam was shown to be an important metabolite of both medazepam and diazepam: the ratio of medazepam to noradiazepam was 0.14 and the ratio of diazepam to nordiazepam following diazepam administration was 0.72. 4. No significant correlations were found between the plasma concentrations of any of the treatments and the clinical ratings or behavioural measures. 5. Some relationship was shown between levels of medazepam and its physiological effects."}
{"id": "PMID:14663", "title": "Conformational transition accompanying the binding of Ca2+ to the protein activator of 3',5'-cyclic adenosine monophosphate phosphodiesterase.", "content": "The Ca2+-dependent protein activator of 3':5'-cyclic adenosine monophosphate phosphodiesterase is shown to undergo a conformational transition upon binding of 2 mol of Ca2+/mol of activator. Circular dichroic studies indicate that Ca2+ induces an increase of 5-8% in alpha-helix content with a concomitant decrease in the amount of random coil. In the absence of Ca2+ and in the presence of [ethylenebis(oxoethylenenitrilo)]tetraacetic acid (EGTA), the protein contains 30-35% alpha helix, 50% random coil, and 15-20% beta-pleated sheat. Spectrophotometric titration indicates that the two tyrosyl residues have pK's of 10.4 and 11.9 and are therefore in different environments. The Ca2+-induced conformational change is accompanied by an increased exposure to protons of the partially exposed tyrosine, as shown by a shift in its pK from 10.4 to 10.). Increased solvation is also consistent with a negative difference spectrum at 287 and 279 nm as seen upon Ca2+ binding. Modification in the environment of all or some of the phenylalanine residues also is part of the conformational change accompanying Ca2+ binding. A new and rapid purification procedure which yields large amounts (25-30% yields) of homogenous protein activator and a direct and sensitive assay procedure for cAMP phosphodiesterase and its activator are also described.", "contents": "Conformational transition accompanying the binding of Ca2+ to the protein activator of 3',5'-cyclic adenosine monophosphate phosphodiesterase. The Ca2+-dependent protein activator of 3':5'-cyclic adenosine monophosphate phosphodiesterase is shown to undergo a conformational transition upon binding of 2 mol of Ca2+/mol of activator. Circular dichroic studies indicate that Ca2+ induces an increase of 5-8% in alpha-helix content with a concomitant decrease in the amount of random coil. In the absence of Ca2+ and in the presence of [ethylenebis(oxoethylenenitrilo)]tetraacetic acid (EGTA), the protein contains 30-35% alpha helix, 50% random coil, and 15-20% beta-pleated sheat. Spectrophotometric titration indicates that the two tyrosyl residues have pK's of 10.4 and 11.9 and are therefore in different environments. The Ca2+-induced conformational change is accompanied by an increased exposure to protons of the partially exposed tyrosine, as shown by a shift in its pK from 10.4 to 10.). Increased solvation is also consistent with a negative difference spectrum at 287 and 279 nm as seen upon Ca2+ binding. Modification in the environment of all or some of the phenylalanine residues also is part of the conformational change accompanying Ca2+ binding. A new and rapid purification procedure which yields large amounts (25-30% yields) of homogenous protein activator and a direct and sensitive assay procedure for cAMP phosphodiesterase and its activator are also described."}
{"id": "PMID:14664", "title": "The electrochemical proton gradient in Escherichia coli membrane vesicles.", "content": "Membrane vesicles isolated from Escherichia coli grown under various conditions generate a transmembrane pH gradient (delta pH) of about 2 pH units (interior alkaline) under appropriate conditions when assayed by flow dialysis. Using the distribution of weak acids to measure delta pH and the distribution of the lipophilic cation triphenylmethylphosphonium to measure the electrical potential (delta psi) across the membrane, the vesicles are demonstrated to develop an electrochemical proton gradient (delta-muH+) of almost - 200 mV (interior negative and alkaline) at pH 5.5 in the presence of reduced phenazine methosulfate or D-lactate, the major component of which is a deltapH of about - 120 mV. As external pH is increased, deltapH decreases, reaching 0 at about pH 7.5 and above, while delta psi remains at about - 75 mV and internal pH remains at pH 7.5-7.8. The variations in deltapH correlate with changes in the oxidation of reduced phenazine methosulfate or D-lactate, both of which vary with external pH in a manner similar to that described for deltapH. Finally, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin with little change in delta-muH+ and no change in respiratory activity. These data and those presented in the following paper (Ramos and Kaback 1976) provide strong support for the role of chemiosmotic phenomena in active transport and extend certain aspects of the chemiosmotic hypothesis.", "contents": "The electrochemical proton gradient in Escherichia coli membrane vesicles. Membrane vesicles isolated from Escherichia coli grown under various conditions generate a transmembrane pH gradient (delta pH) of about 2 pH units (interior alkaline) under appropriate conditions when assayed by flow dialysis. Using the distribution of weak acids to measure delta pH and the distribution of the lipophilic cation triphenylmethylphosphonium to measure the electrical potential (delta psi) across the membrane, the vesicles are demonstrated to develop an electrochemical proton gradient (delta-muH+) of almost - 200 mV (interior negative and alkaline) at pH 5.5 in the presence of reduced phenazine methosulfate or D-lactate, the major component of which is a deltapH of about - 120 mV. As external pH is increased, deltapH decreases, reaching 0 at about pH 7.5 and above, while delta psi remains at about - 75 mV and internal pH remains at pH 7.5-7.8. The variations in deltapH correlate with changes in the oxidation of reduced phenazine methosulfate or D-lactate, both of which vary with external pH in a manner similar to that described for deltapH. Finally, deltapH and delta psi can be varied reciprocally in the presence of valinomycin and nigericin with little change in delta-muH+ and no change in respiratory activity. These data and those presented in the following paper (Ramos and Kaback 1976) provide strong support for the role of chemiosmotic phenomena in active transport and extend certain aspects of the chemiosmotic hypothesis."}
{"id": "PMID:14665", "title": "The relationship between the electrochemical proton gradient and active transport in Escherichia coli membrane vesicles.", "content": "In the previous paper [ramos, S., and Kaback, H.R. (1977), Biochemistry 16 (preceding paper in this issue)], it was demonstrated that Escherichia coli membrane vesicles generate a large electrochemical proton gradient (delta-muH+) under appropriate conditions, and some of the properties of delta-muH+ and its component forces [i.e., the membrane potential (delta psi) and the chemical gradient of protons (deltapH)] were described. In this paper, the relationship between delta-muH+, delta psi, and deltapH and the active transport of specific solutes is examined. Addition of lactose or glucose 6-phosphate to membrane vesicles containing the appropriate transport systems results in partial collapse of deltapH, providing direct evidence for the suggestion that respiratory energy can drive active transport via the pH gradient across the membrane. Titration studies with valinomycin and nigericin lead to the conclusion that, at pH 5.5, there are two general classes of transport systems: those that are driven primarily by delta-muH+ (lactose, proline, serine, glycine, tyrosine, glutamate, leucine, lysine, cysteine, and succinate) and those that are driven primarily by deltapH (glucose 6-phosphate, D-lactate, glucuronate, and gluconate). Importantly, however, it is also demonstrated that at pH 7.5, all of these transport systems are driven by delta psi which comprises the only component of delta-muH+ at this external pH. In addition, the effect of external pH on the steady-state levels of accumulation of different solutes is examined, and it is shown that none of the pH profiles correspond to those observed for delta-muH+, delta psi, or deltapH. Moreover, at external pH values above 6.0-6.5, delta-muH+ is insufficient to account for the concentration gradients established for each substrate unless the stoichiometry between protons and accumulated solutes is greater than unity. The results confirm many facets of the chemiosmotic hypothesis, but they also extend the concept in certain important respects and allow explanations for some earlier observations which seemed to preclude the involvement of chemiosmotic phenomena in active transport.", "contents": "The relationship between the electrochemical proton gradient and active transport in Escherichia coli membrane vesicles. In the previous paper [ramos, S., and Kaback, H.R. (1977), Biochemistry 16 (preceding paper in this issue)], it was demonstrated that Escherichia coli membrane vesicles generate a large electrochemical proton gradient (delta-muH+) under appropriate conditions, and some of the properties of delta-muH+ and its component forces [i.e., the membrane potential (delta psi) and the chemical gradient of protons (deltapH)] were described. In this paper, the relationship between delta-muH+, delta psi, and deltapH and the active transport of specific solutes is examined. Addition of lactose or glucose 6-phosphate to membrane vesicles containing the appropriate transport systems results in partial collapse of deltapH, providing direct evidence for the suggestion that respiratory energy can drive active transport via the pH gradient across the membrane. Titration studies with valinomycin and nigericin lead to the conclusion that, at pH 5.5, there are two general classes of transport systems: those that are driven primarily by delta-muH+ (lactose, proline, serine, glycine, tyrosine, glutamate, leucine, lysine, cysteine, and succinate) and those that are driven primarily by deltapH (glucose 6-phosphate, D-lactate, glucuronate, and gluconate). Importantly, however, it is also demonstrated that at pH 7.5, all of these transport systems are driven by delta psi which comprises the only component of delta-muH+ at this external pH. In addition, the effect of external pH on the steady-state levels of accumulation of different solutes is examined, and it is shown that none of the pH profiles correspond to those observed for delta-muH+, delta psi, or deltapH. Moreover, at external pH values above 6.0-6.5, delta-muH+ is insufficient to account for the concentration gradients established for each substrate unless the stoichiometry between protons and accumulated solutes is greater than unity. The results confirm many facets of the chemiosmotic hypothesis, but they also extend the concept in certain important respects and allow explanations for some earlier observations which seemed to preclude the involvement of chemiosmotic phenomena in active transport."}
{"id": "PMID:14666", "title": "Studies of individual carbon sites of azurin from Pseudomonas aeruginosa by natural-abundance carbon-13 nuclear magnetic resonance spectroscopy.", "content": "The environments of the aromatic residues (and of the single arginine residue) of azurin from Pseudomonas aeruginosa are investigated by means of natural-abundance 13C Fourier transform NMR spectroscopy. In the case of the diamagnetic Cu(I) azurin, all 17 nonprotonated aromatic carbons (and Czota of Arg-79) yield narrow resonances. Furthermore, a single-carbon amide carbonyl resonance with an unusual chemical shift (peak chi) is observed. The pH dependence of chemical shifts is used to identify the resonances of Cgamma of titrating histidines, and of Cgamma and Czota of the two tyrosines. The resonances of Cgamma and Cdelta2 of the single tryptophan residue (and Czota of Arg-79) are also identified. The pKa values of the two tyrosines are different from each other and higher than typical values of \"solvent-exposed\" tyrosine residues. Two of the four histidine residues do not titrate (in the pH range 4 to 11). The resonance of Cgamma of one histidine exhibits a pH titration with fast proton exchange behavior and a pKa of 7.5 +/- 0.2. The direction of the titration shift indicates that the imidazole form of this histidine is the Ndelta1-H tautomer. The Cgamma resonance of the other titrating histidine exhibits slow exchange behavior with a pKa of about 7. The imidazole form of this histidine is the Nepsilon2-H tautomer. When going to the paramagnetic Cu(II) protein, only 11 of the 19 carbons mentioned above yield resonances that are narrow enough to be detected. Also, some of the observed resonances exhibit significant paramagnetic broadening. A comparison of spectra of fully reduced azurin, mixtures of reduced and oxidized azurin, and fully oxidized azurin yields the following information. (i) Peak chi arises from an amide group that probably is coordinated to the copper. (ii) The two nontitrating histidine residues are probably copper ligands, with Ndelta1 coordinated to the metal. (iii) The side chains of Arg-79 and the two tyrosine residues are not coordinated to the copper, and Trp-48 is probably not a ligand either. (iv) The gamma carbons of Trp-48, the tyrosine with the lower pKa, the titrating histidine with slow exchange behavior, and three or four of the six phenylalanine residues are sufficiently close to the copper to undergo significant paramagnetic broadening in the spectrum of oxidized azurin.", "contents": "Studies of individual carbon sites of azurin from Pseudomonas aeruginosa by natural-abundance carbon-13 nuclear magnetic resonance spectroscopy. The environments of the aromatic residues (and of the single arginine residue) of azurin from Pseudomonas aeruginosa are investigated by means of natural-abundance 13C Fourier transform NMR spectroscopy. In the case of the diamagnetic Cu(I) azurin, all 17 nonprotonated aromatic carbons (and Czota of Arg-79) yield narrow resonances. Furthermore, a single-carbon amide carbonyl resonance with an unusual chemical shift (peak chi) is observed. The pH dependence of chemical shifts is used to identify the resonances of Cgamma of titrating histidines, and of Cgamma and Czota of the two tyrosines. The resonances of Cgamma and Cdelta2 of the single tryptophan residue (and Czota of Arg-79) are also identified. The pKa values of the two tyrosines are different from each other and higher than typical values of \"solvent-exposed\" tyrosine residues. Two of the four histidine residues do not titrate (in the pH range 4 to 11). The resonance of Cgamma of one histidine exhibits a pH titration with fast proton exchange behavior and a pKa of 7.5 +/- 0.2. The direction of the titration shift indicates that the imidazole form of this histidine is the Ndelta1-H tautomer. The Cgamma resonance of the other titrating histidine exhibits slow exchange behavior with a pKa of about 7. The imidazole form of this histidine is the Nepsilon2-H tautomer. When going to the paramagnetic Cu(II) protein, only 11 of the 19 carbons mentioned above yield resonances that are narrow enough to be detected. Also, some of the observed resonances exhibit significant paramagnetic broadening. A comparison of spectra of fully reduced azurin, mixtures of reduced and oxidized azurin, and fully oxidized azurin yields the following information. (i) Peak chi arises from an amide group that probably is coordinated to the copper. (ii) The two nontitrating histidine residues are probably copper ligands, with Ndelta1 coordinated to the metal. (iii) The side chains of Arg-79 and the two tyrosine residues are not coordinated to the copper, and Trp-48 is probably not a ligand either. (iv) The gamma carbons of Trp-48, the tyrosine with the lower pKa, the titrating histidine with slow exchange behavior, and three or four of the six phenylalanine residues are sufficiently close to the copper to undergo significant paramagnetic broadening in the spectrum of oxidized azurin."}
{"id": "PMID:14667", "title": "Active proton uptake by chromaffin granules: observation by amine distribution and phosphorus-31 nuclear magnetic resonance techniques.", "content": "The hydrogen ion activity within isolated chromaffin granules can be estimated from the distribution of the weak base methylamine and from phosphorus-31 nuclear magnetic resonance spectra of ATP contained in the granules. Following the addition of ATP to the external medium, the internal pH drops by 0.2 to 0.5 unit. This change occurs only in medium containing a permeant anion such as chloride and is abolished by an uncoupler of oxidative phosphorylation. These results indicate that the chromaffin granule membrane possess an electrogenic proton pump directed inward.", "contents": "Active proton uptake by chromaffin granules: observation by amine distribution and phosphorus-31 nuclear magnetic resonance techniques. The hydrogen ion activity within isolated chromaffin granules can be estimated from the distribution of the weak base methylamine and from phosphorus-31 nuclear magnetic resonance spectra of ATP contained in the granules. Following the addition of ATP to the external medium, the internal pH drops by 0.2 to 0.5 unit. This change occurs only in medium containing a permeant anion such as chloride and is abolished by an uncoupler of oxidative phosphorylation. These results indicate that the chromaffin granule membrane possess an electrogenic proton pump directed inward."}
{"id": "PMID:14668", "title": "Determination of the microscopic and macroscopic acid dissociation constants of glycyl-L-histidyl-L-lysine and related histidine peptides.", "content": "Proton magnetic resonance studies of the acid-base chemistry of the glycyl ammonium, histidyl imidazolium, and lysyl ammonium groups of glycyl-L-histidyl-L-lysine and of the glycyl ammonium and histidyl imidazolium groups of glycyl-L-histidine and glycyl-L-histidylglycine are described. Chemical-shift data indicate that, at the molecular level, the glycyl ammonium and the histidyl imidazolium groups are titrated over the same pH range, with the acidity of the imidazolium group some 8 to 10 times that of the glycyl ammonium group, depending on the peptide. The lysyl ammonium group of Gly-His-Lys is much less acidic and is titrated over a higher pH range. Microscopic and macroscopic acid-dissociation constants were determined from chemical-shift data for each of the peptides. It is shown how microscopic formation constants for protonated metal complexes of these ligands, which are being used increasingly as models for the binding of metal ions by proteins, can be calculated from the macroscopic formation constants and the microscopic acid-dissociation constants. The acid-base chemistry of Gly-His-Lys is discussed with respect to its recently discovered biological activity.", "contents": "Determination of the microscopic and macroscopic acid dissociation constants of glycyl-L-histidyl-L-lysine and related histidine peptides. Proton magnetic resonance studies of the acid-base chemistry of the glycyl ammonium, histidyl imidazolium, and lysyl ammonium groups of glycyl-L-histidyl-L-lysine and of the glycyl ammonium and histidyl imidazolium groups of glycyl-L-histidine and glycyl-L-histidylglycine are described. Chemical-shift data indicate that, at the molecular level, the glycyl ammonium and the histidyl imidazolium groups are titrated over the same pH range, with the acidity of the imidazolium group some 8 to 10 times that of the glycyl ammonium group, depending on the peptide. The lysyl ammonium group of Gly-His-Lys is much less acidic and is titrated over a higher pH range. Microscopic and macroscopic acid-dissociation constants were determined from chemical-shift data for each of the peptides. It is shown how microscopic formation constants for protonated metal complexes of these ligands, which are being used increasingly as models for the binding of metal ions by proteins, can be calculated from the macroscopic formation constants and the microscopic acid-dissociation constants. The acid-base chemistry of Gly-His-Lys is discussed with respect to its recently discovered biological activity."}
{"id": "PMID:14669", "title": "Glutamine active site of formylglycinamide ribonucleotide amidotransferase. 1. Labeling of the enzyme with iodoacetate.", "content": "A two-step method for labeling the glutamine active site of formyglycinamide ribonucleotide (FGAR) amidotransferase from chicken liver has been developed in which reaction of all other reactive groups with unlabeled iodoacetate is followed by specific labeling of the glutamine site with radioactive reagent. A study of the reaction as a function of duration, temperature, and pH of the incubation as well as concentration of iodoacetate has revealed that two nonessential groups of the enzyme react in the presence of glutamine and that this modified enzyme is relatively resistant to further carboxymethylation. When this modified enzyme was incubated with radioactive iodoacetate in the presence of FGAR, ATP, and Mg2+ after removal of glutamine by dialysis, about 1 mol of radioactive iodoacetate was incorporated per mol of enzyme with inactivation. This method permits labeling of the active site for glutamine without the use of glutamine analogues.", "contents": "Glutamine active site of formylglycinamide ribonucleotide amidotransferase. 1. Labeling of the enzyme with iodoacetate. A two-step method for labeling the glutamine active site of formyglycinamide ribonucleotide (FGAR) amidotransferase from chicken liver has been developed in which reaction of all other reactive groups with unlabeled iodoacetate is followed by specific labeling of the glutamine site with radioactive reagent. A study of the reaction as a function of duration, temperature, and pH of the incubation as well as concentration of iodoacetate has revealed that two nonessential groups of the enzyme react in the presence of glutamine and that this modified enzyme is relatively resistant to further carboxymethylation. When this modified enzyme was incubated with radioactive iodoacetate in the presence of FGAR, ATP, and Mg2+ after removal of glutamine by dialysis, about 1 mol of radioactive iodoacetate was incorporated per mol of enzyme with inactivation. This method permits labeling of the active site for glutamine without the use of glutamine analogues."}
{"id": "PMID:14670", "title": "Solvent effects on thiamin-enzyme model interactions. I. Interactions with tryptophan.", "content": "The solvent polarity dependence of the interaction between thiamin and tryptophan was studied by spectrophotometric methods. The ultraviolet (UV) data clearly indicate that the interaction is weakened when the complex is transferred from water to aqueous ethanol or aqueous dioxane. The interaction of thiamin and tryptophan could also be detected by fluorescence-quenching studies (excitation of tryptophan at 287 nm, maximum emission at 348 nm). Appropriate treatment of the quenching data allowed dissection into static and dynamic contributions. A pyrimidine derivative related to thiamin, both in its neutral and protonated states, was shown to interact with tryptophan by fluorescence techniques, but not by UV. A thiazolium model was shown to interact with tryptophan by UV but was an inefficient quencher of the tryptophan fluorescence. Theoretical models are presented to explain the solvent dielectric constant dependence of the association constant between tryptophan and thiamin. Both electrostatic and dispersion forces are found to contribute to the stability of the complex.", "contents": "Solvent effects on thiamin-enzyme model interactions. I. Interactions with tryptophan. The solvent polarity dependence of the interaction between thiamin and tryptophan was studied by spectrophotometric methods. The ultraviolet (UV) data clearly indicate that the interaction is weakened when the complex is transferred from water to aqueous ethanol or aqueous dioxane. The interaction of thiamin and tryptophan could also be detected by fluorescence-quenching studies (excitation of tryptophan at 287 nm, maximum emission at 348 nm). Appropriate treatment of the quenching data allowed dissection into static and dynamic contributions. A pyrimidine derivative related to thiamin, both in its neutral and protonated states, was shown to interact with tryptophan by fluorescence techniques, but not by UV. A thiazolium model was shown to interact with tryptophan by UV but was an inefficient quencher of the tryptophan fluorescence. Theoretical models are presented to explain the solvent dielectric constant dependence of the association constant between tryptophan and thiamin. Both electrostatic and dispersion forces are found to contribute to the stability of the complex."}
{"id": "PMID:14671", "title": "NADPH-cytochrome P-450 reductase from rat liver: purification by affinity chromatography and characterization.", "content": "(NADPH)-cytochrome P-450 reductase was purified to apparent homogeneity by a procedure utilizing nicotinamide adenine dinucleotide phosphate (NADP)-Sepharose affinity column chromatography. The purified flavoprotein has a molecular weight of 79 700 and catalyzes cytochrome P-450 dependent drug metabolism, as well as reduction of exogenous electron acceptors. Aerobic titration of cytochrome P-450 reductase with NADPH indicates that an air-stable reduced form of the enzyme is generated by the addition of 0.5 mol of NADPH per mole of flavin, as judged by spectral characteristics. Further addition of NADPH causes no other changes in the absorbance spectrum. A Km value for NADPH of 5 micron was observed when either cytochrome P-450 or cytochrome c was employed as electron acceptor. A Km value of 8 +/- 2 micron was determined for cytochrome c and a Km of 0.09 +/- 0.01 micron was estimated for cytochrome P-450.", "contents": "NADPH-cytochrome P-450 reductase from rat liver: purification by affinity chromatography and characterization. (NADPH)-cytochrome P-450 reductase was purified to apparent homogeneity by a procedure utilizing nicotinamide adenine dinucleotide phosphate (NADP)-Sepharose affinity column chromatography. The purified flavoprotein has a molecular weight of 79 700 and catalyzes cytochrome P-450 dependent drug metabolism, as well as reduction of exogenous electron acceptors. Aerobic titration of cytochrome P-450 reductase with NADPH indicates that an air-stable reduced form of the enzyme is generated by the addition of 0.5 mol of NADPH per mole of flavin, as judged by spectral characteristics. Further addition of NADPH causes no other changes in the absorbance spectrum. A Km value for NADPH of 5 micron was observed when either cytochrome P-450 or cytochrome c was employed as electron acceptor. A Km value of 8 +/- 2 micron was determined for cytochrome c and a Km of 0.09 +/- 0.01 micron was estimated for cytochrome P-450."}
{"id": "PMID:14672", "title": "Isotope effect studies of the role of metal ions in isocitrate dehydrogenase.", "content": "Pig heart NADP+-dependent isocitrate dehydrogenase requires a metal ion for activity. Under optimum conditions (pH 7.5, Mg2+ present), the carbon isotope effect is k12/k13 = 0.9989 +/- 0.0004 for the carboxyl carbon undergoing decarboxylation and hydrogen isotope effects are VmaxH/VmaxD = 1.09 +/- 0.04 and (Vmax/Km)H/(Vmax/Km)D = 0.76 +/- 0.12 with threo-D,L-[2-2H]isocitric acid. Deuterium isotope effects measured by the equilibrium perturbation technique under the same conditions are VH/VD = 1.20 for the forward reaction and 1.02 for the reverse reaction. Under these conditions the rate-determining step in the enzymatic reaction must be product release. Dissociation of isocitrate from the enzyme-isocitrate complex and the enzyme-NADP+ complex must be two or more orders of magnitude slower than the chemical steps. The catalytic activity of the enzyme is about tenfold lower in the presence of Ni2+ than in the presence of Mg2+. The carbon isotope effect in the presence of Ni2+ at pH 7.5 is k12/k13 = 1.0051 +/- 0.0012 and the hydrogen isotope effects are VmaxH/VmaxD = 0.98 +/- 0.07 and (Vmax/Km)H/(Vmax/Km)D = 1.11 +/- 0.14. Thus, the rate decrease caused by substitution of Ni2+ for Mg2+ must result from the effects of metal on substrate and product binding and dissociation, rather than effects of metal on catalysis. However, a more detailed analysis of the carbon isotope effects reveals that there is also a large metal effect on the rate of the decarboxylation step, consistent with the view that the carbonyl oxygen of the oxalosuccinate intermediate is coordinated to the metal during decarboxylation.", "contents": "Isotope effect studies of the role of metal ions in isocitrate dehydrogenase. Pig heart NADP+-dependent isocitrate dehydrogenase requires a metal ion for activity. Under optimum conditions (pH 7.5, Mg2+ present), the carbon isotope effect is k12/k13 = 0.9989 +/- 0.0004 for the carboxyl carbon undergoing decarboxylation and hydrogen isotope effects are VmaxH/VmaxD = 1.09 +/- 0.04 and (Vmax/Km)H/(Vmax/Km)D = 0.76 +/- 0.12 with threo-D,L-[2-2H]isocitric acid. Deuterium isotope effects measured by the equilibrium perturbation technique under the same conditions are VH/VD = 1.20 for the forward reaction and 1.02 for the reverse reaction. Under these conditions the rate-determining step in the enzymatic reaction must be product release. Dissociation of isocitrate from the enzyme-isocitrate complex and the enzyme-NADP+ complex must be two or more orders of magnitude slower than the chemical steps. The catalytic activity of the enzyme is about tenfold lower in the presence of Ni2+ than in the presence of Mg2+. The carbon isotope effect in the presence of Ni2+ at pH 7.5 is k12/k13 = 1.0051 +/- 0.0012 and the hydrogen isotope effects are VmaxH/VmaxD = 0.98 +/- 0.07 and (Vmax/Km)H/(Vmax/Km)D = 1.11 +/- 0.14. Thus, the rate decrease caused by substitution of Ni2+ for Mg2+ must result from the effects of metal on substrate and product binding and dissociation, rather than effects of metal on catalysis. However, a more detailed analysis of the carbon isotope effects reveals that there is also a large metal effect on the rate of the decarboxylation step, consistent with the view that the carbonyl oxygen of the oxalosuccinate intermediate is coordinated to the metal during decarboxylation."}
{"id": "PMID:14673", "title": "pH-dependent Soret difference spectra of the deoxy and carbonmonoxy forms of human hemoglobin and its derivatives.", "content": "The transition from deoxy to oxystructure of hemoglobin A (Hb) is accompanied by the breaking of the salt bridges formed by C-terminal residues in deoxy-Hb. This, in turn, changes the state of the heme. The switch between these different allosteric forms can be followed by changes in the optical absorbance spectra (Perutz, M. F., Ladner, J. E., Simon, S. R., and Ho, C. (1974), Biochemistry 13, 2163). Using difference spectroscopy in the soret region, pH-dependent spectral changes of Hb and its derivatives (carbamylated at both the alpha-NH2 groups, alpha2cbeta2c; N-ethylsuccinimide hemoglobin, NES-Hb) in their deoxy and carbonmonoxy forms were measured. From these measurements, the pK values of histidine-146beta and valine-1alpha in deoxy-Hb were determined to be 8.6 +/- 0.2 and 7.7 +/- 0.1, respectively. In carbonmonoxy-Hb a pK value of 6.3 +/- 0.1 was found.", "contents": "pH-dependent Soret difference spectra of the deoxy and carbonmonoxy forms of human hemoglobin and its derivatives. The transition from deoxy to oxystructure of hemoglobin A (Hb) is accompanied by the breaking of the salt bridges formed by C-terminal residues in deoxy-Hb. This, in turn, changes the state of the heme. The switch between these different allosteric forms can be followed by changes in the optical absorbance spectra (Perutz, M. F., Ladner, J. E., Simon, S. R., and Ho, C. (1974), Biochemistry 13, 2163). Using difference spectroscopy in the soret region, pH-dependent spectral changes of Hb and its derivatives (carbamylated at both the alpha-NH2 groups, alpha2cbeta2c; N-ethylsuccinimide hemoglobin, NES-Hb) in their deoxy and carbonmonoxy forms were measured. From these measurements, the pK values of histidine-146beta and valine-1alpha in deoxy-Hb were determined to be 8.6 +/- 0.2 and 7.7 +/- 0.1, respectively. In carbonmonoxy-Hb a pK value of 6.3 +/- 0.1 was found."}
{"id": "PMID:14674", "title": "Acid-catalyzed hydration of reduced nicotinamide adenine dinucleotide and its analogues.", "content": "The rate of the primary acid modification reaction of 1,4-dihydronicotinamide adenine dinucleotide (NADH) and 1,4-dihydro-3-acetylpyridine adenine dinucleotide (APADH) and their analogues has been studied over a wide pH range (pH 1-7) with a variety of general acid catalysts. The rate depends on [H+] at moderate pH and becomes independent of [H+] at low pH. This behavior is attributed to substrate protonation at the carbonyl group (pK of NADH = 0.6). The reaction is general acid catalyzed; large solvent deuterium isotope effects are observed for the general acid and lyonium ion terms. Most buffers cause a linear rate increase with increasing buffer concentration, but certain buffers cause a hyperbolic rate increase. The nonlinear buffer effects are due to complexation of the buffer with the substrate, rather than to a change in rate-limiting step. The rate-limiting step is a proton transfer from the general acid species to the C5 position of the substrate. Anomerization is not a necessary first step in the case of the primary acid modification reaction of beta-NADH, in which beta to alpha anomerization takes place.", "contents": "Acid-catalyzed hydration of reduced nicotinamide adenine dinucleotide and its analogues. The rate of the primary acid modification reaction of 1,4-dihydronicotinamide adenine dinucleotide (NADH) and 1,4-dihydro-3-acetylpyridine adenine dinucleotide (APADH) and their analogues has been studied over a wide pH range (pH 1-7) with a variety of general acid catalysts. The rate depends on [H+] at moderate pH and becomes independent of [H+] at low pH. This behavior is attributed to substrate protonation at the carbonyl group (pK of NADH = 0.6). The reaction is general acid catalyzed; large solvent deuterium isotope effects are observed for the general acid and lyonium ion terms. Most buffers cause a linear rate increase with increasing buffer concentration, but certain buffers cause a hyperbolic rate increase. The nonlinear buffer effects are due to complexation of the buffer with the substrate, rather than to a change in rate-limiting step. The rate-limiting step is a proton transfer from the general acid species to the C5 position of the substrate. Anomerization is not a necessary first step in the case of the primary acid modification reaction of beta-NADH, in which beta to alpha anomerization takes place."}
{"id": "PMID:14675", "title": "Phosphatidic acid distribution on the external surface of mixed vesicles.", "content": "A new method has been developed to detect the distribution of phosphatidic acid on the external surface of mixed phospholipid vesicles. Some positive dyes undergo large absorbance changes when the spatial separation between two or more dye molecules is smaller than a critical distance. When these dyes interact with mixed phospholipid vesicles, the absorbance changes may be utilized to calculate the amount of phosphatidic acid molecules which, on the external surface, occupy nearby positions not exceeding the critical dye distance, i.e., the amount of paired phosphatidic acid molecules. This amount was found to be higher than that calculated by statistical methods, indicating that phosphatidic acid molecules tend to be associated, in spite of the electrostatic repulsion between negative groups. The dependence of the amount of paired phosphatidic acid molecules on the pH, phosphatidylcholine:phosphatidic acid ratio, and temperature has been also analyzed.", "contents": "Phosphatidic acid distribution on the external surface of mixed vesicles. A new method has been developed to detect the distribution of phosphatidic acid on the external surface of mixed phospholipid vesicles. Some positive dyes undergo large absorbance changes when the spatial separation between two or more dye molecules is smaller than a critical distance. When these dyes interact with mixed phospholipid vesicles, the absorbance changes may be utilized to calculate the amount of phosphatidic acid molecules which, on the external surface, occupy nearby positions not exceeding the critical dye distance, i.e., the amount of paired phosphatidic acid molecules. This amount was found to be higher than that calculated by statistical methods, indicating that phosphatidic acid molecules tend to be associated, in spite of the electrostatic repulsion between negative groups. The dependence of the amount of paired phosphatidic acid molecules on the pH, phosphatidylcholine:phosphatidic acid ratio, and temperature has been also analyzed."}
{"id": "PMID:14676", "title": "Duplex formation of a nonionic oligo(deoxythymidylate) analogue (heptadeoxythymidylyl-(3'-5')-deoxythymidine heptaethyl ester (d-(Tp(Et))7T)) with poly(deoxyadenylate). Evaluation of the electrostatic interaction.", "content": "The heptaethyl ester of heptadeoxythymidylyl-(3'-5')-deoxythymidine (d-[Tp(Et)]7T or d-T8-Et) has been prepared by chemical methods. The material, consisting of a mixture of diastereoisomers, forms a 1:1 complex with (dA)n in neutral aqueous buffer; this interaction is virtually independent of ionic strength. The octamer triester does not bind to (dA)n-(dT)n, and it interacts with (rA)n only at low temperatures. By cochromatography with (dA)n on Sephadex G-50, d-T8-Et fractions with different binding affinities for the polyadenylates were obtained. This heterogeneity in binding affinity is ascribed to the diastereoisomerism of d-T8-Et. Enthalpies of dupoex formation were determined by the concentration variation method. At 0.1 M sodium ion concentration, the enthalpy of binding of the various d-T8-Et fractions to (dA)n is essentially invariant (-8.1 kcal/mol of base pairs at 0 degrees C to -8.6 kcal at 25 degrees C) and 1.6 kcal/mol of base pairs more negative than the enthalpy of binding of the phosphodiester analogue, d-(Tp)7T, to (dA)n (-6.8 kcal/mol of base pairs at 11 degrees C). This difference is the electrostatic contribution to the enthalpy of duplex formation, arising from the interstrand electrostatic repulsion and the intrastrand repulsion in d-(Tp)7T. The entropy of binding to (dA)n is more negative for the octamer triesters than for the diester analogue, and is different for the various d-T8-Et fractions. This is interpreted in terms of varying degrees of restriction of rotational freedom for the ethyl substituents upon double helix formation.", "contents": "Duplex formation of a nonionic oligo(deoxythymidylate) analogue (heptadeoxythymidylyl-(3'-5')-deoxythymidine heptaethyl ester (d-(Tp(Et))7T)) with poly(deoxyadenylate). Evaluation of the electrostatic interaction. The heptaethyl ester of heptadeoxythymidylyl-(3'-5')-deoxythymidine (d-[Tp(Et)]7T or d-T8-Et) has been prepared by chemical methods. The material, consisting of a mixture of diastereoisomers, forms a 1:1 complex with (dA)n in neutral aqueous buffer; this interaction is virtually independent of ionic strength. The octamer triester does not bind to (dA)n-(dT)n, and it interacts with (rA)n only at low temperatures. By cochromatography with (dA)n on Sephadex G-50, d-T8-Et fractions with different binding affinities for the polyadenylates were obtained. This heterogeneity in binding affinity is ascribed to the diastereoisomerism of d-T8-Et. Enthalpies of dupoex formation were determined by the concentration variation method. At 0.1 M sodium ion concentration, the enthalpy of binding of the various d-T8-Et fractions to (dA)n is essentially invariant (-8.1 kcal/mol of base pairs at 0 degrees C to -8.6 kcal at 25 degrees C) and 1.6 kcal/mol of base pairs more negative than the enthalpy of binding of the phosphodiester analogue, d-(Tp)7T, to (dA)n (-6.8 kcal/mol of base pairs at 11 degrees C). This difference is the electrostatic contribution to the enthalpy of duplex formation, arising from the interstrand electrostatic repulsion and the intrastrand repulsion in d-(Tp)7T. The entropy of binding to (dA)n is more negative for the octamer triesters than for the diester analogue, and is different for the various d-T8-Et fractions. This is interpreted in terms of varying degrees of restriction of rotational freedom for the ethyl substituents upon double helix formation."}
{"id": "PMID:14677", "title": "Biosynthesis of spin-labeled peptidoglycan: spin-spin interactions.", "content": "Membrane preparations from Gaffkya homari catalyzed the in vitro biosynthesis of soluble uncross-linked spin-labeled peptidoglycan, a uniformly labeled polynitroxide, from the spin-labeled nucleotide UDP-MurNAc-Ala-DGlu-Lys(Nepsilon-2,2,5,5-tetramethyl-1-pyrrolin-1-oxyl-3-carbonyl)-DAla-DAla (I) and UDP-GlcNAc. Soluble spin-labeled peptidoglycan was separated from membrane fragments and its spin-labeled precursor by centrifugation and gel filtration. The molecular weight distribution of the polymer was examined by agarose gel filtration. Spin-labeled [14C]peptidoglycan was polydisperse with a peak of radioactivity corresponding to a molecular weight of 5.0 X 10(5). The electron spin resonance spectrum of spin-labeled peptidoglycan was extensively broadened by spin-spin exchange interactions. These interactions were modified by changes in temperature, reduction by ascorbate, hydrolysis by lysozyme, and complexation with the antibiotic, vancomycin. Spin-spin exchange was reduced or eliminated in spin-labeled peptidoglycan by the random reduction of free radicals by ascorbate. A rotational correlation time of 0.37 ns was calculated for the probe in partially reduced spin-labeled peptidoglycan. This compares to a correlation time of 0.13 ns for the substrate (I). Raising the temperature increases spin-spin exchange line broadening. No transition points were observed for spin-labeled peptidoglycan as measured by this method. Degradati on of spin-labeled peptidoglycan by lysozyme eliminated the observed spin-spin exchange and yielded products with a mobility similar to I. Complexation of spin-labeled peptidoglycan with vancomycin resulted in both pronounced free-radical immobilization and a decrease in spin-spin exchange. The exchange effects are consistent with distance measurements in molecular models for peptidoglycan.", "contents": "Biosynthesis of spin-labeled peptidoglycan: spin-spin interactions. Membrane preparations from Gaffkya homari catalyzed the in vitro biosynthesis of soluble uncross-linked spin-labeled peptidoglycan, a uniformly labeled polynitroxide, from the spin-labeled nucleotide UDP-MurNAc-Ala-DGlu-Lys(Nepsilon-2,2,5,5-tetramethyl-1-pyrrolin-1-oxyl-3-carbonyl)-DAla-DAla (I) and UDP-GlcNAc. Soluble spin-labeled peptidoglycan was separated from membrane fragments and its spin-labeled precursor by centrifugation and gel filtration. The molecular weight distribution of the polymer was examined by agarose gel filtration. Spin-labeled [14C]peptidoglycan was polydisperse with a peak of radioactivity corresponding to a molecular weight of 5.0 X 10(5). The electron spin resonance spectrum of spin-labeled peptidoglycan was extensively broadened by spin-spin exchange interactions. These interactions were modified by changes in temperature, reduction by ascorbate, hydrolysis by lysozyme, and complexation with the antibiotic, vancomycin. Spin-spin exchange was reduced or eliminated in spin-labeled peptidoglycan by the random reduction of free radicals by ascorbate. A rotational correlation time of 0.37 ns was calculated for the probe in partially reduced spin-labeled peptidoglycan. This compares to a correlation time of 0.13 ns for the substrate (I). Raising the temperature increases spin-spin exchange line broadening. No transition points were observed for spin-labeled peptidoglycan as measured by this method. Degradati on of spin-labeled peptidoglycan by lysozyme eliminated the observed spin-spin exchange and yielded products with a mobility similar to I. Complexation of spin-labeled peptidoglycan with vancomycin resulted in both pronounced free-radical immobilization and a decrease in spin-spin exchange. The exchange effects are consistent with distance measurements in molecular models for peptidoglycan."}
{"id": "PMID:14678", "title": "Affinity labeling of rabbit muscle pyruvate kinase by 5'-p-fluorosulfonylbenzoyladenosine.", "content": "Rabbit muscle pyruvate kinase is irreversibly inactivated upon incubation with the adenine nucleotide analogue, 5'-p-fluorosulfonylbenzoyladenosine. A plot of the time dependence of the logarithm of the enzymatic activity at a given time divided by the initial enzymatic activity(logE/Eo) reveals a biphasic rate of inactivation, which is consistent with a rapid reaction to form partially active enzyme having 54% of the original activity, followed by a slower reaction to yield totally inert enzyme. In addition to the pyruvate kinase activity of the enzyme, modification with 5'-p-fluorosulfonylbenzoyladenosine also disrupts its ability to catalyze the decarboxylation of oxaloacetate and the ATP-dependent enolization of pyruvate. In correspondence with the time dependence of inactivation, the rate of incorporation of 5'-p-[14C]fluorosulfonylbenzoyladenosine is also biphasic. Two moles of reagent per mole of enzyme subunit are bound when the enzyme is completely inactive. The pseudo-first-order rate constant for the rapid rate is linearly dependent on reagent concentration, whereas the constant for the slow rate exhibits saturation kinetics, suggesting that the reagent binds reversibly to the second site prior to modification. The adenosine moiety is essential for the effectiveness of 5'-p-fluorosulfonylbenzoyladenosine, since p-fluorosulfonylbenzoic acid does not inactivate pyruvate kinase at a significant rate. Thus, the reaction of 5'-p-fluorosulfonylbenzoyladenosine with pyruvate kinase exhibits several of the characteristics of affinity labeling of the enzyme. Protection against inactivation by 5'-p-fluorosulfonylbenzoyladenosine is provided by the addition to the incubation mixture of phosphoenolpyruvate. Mg-ADP or Mg2+. In contrast, the addition of pyruvate, Mg-ATP, or ADP and ATP alone has no effect on the rate of inactivation. These observations are consistent with the postulate that the 5'-p-fluorosulfonylbenzoyladenosine specifically labels amino acid residues in the binding region of Mg2+ and the phosphoryl group of phosphoenolpyruvate which is transferred during the catalytic reaction. The rate of inactivation increases with increasing pH, and k1 depends on the unprotonated form of an amino acid residue with pK = 8.5. On the basis of the pH dependence of the reaction of pyruvate kinase with 5'-p-fluorosulfonylbenzoyladenosine and the elimination of cysteine residues as possible sites of reaction, it is postulated that lysyl or tyrosyl residues are the most probably candidates for the critical amino acids.", "contents": "Affinity labeling of rabbit muscle pyruvate kinase by 5'-p-fluorosulfonylbenzoyladenosine. Rabbit muscle pyruvate kinase is irreversibly inactivated upon incubation with the adenine nucleotide analogue, 5'-p-fluorosulfonylbenzoyladenosine. A plot of the time dependence of the logarithm of the enzymatic activity at a given time divided by the initial enzymatic activity(logE/Eo) reveals a biphasic rate of inactivation, which is consistent with a rapid reaction to form partially active enzyme having 54% of the original activity, followed by a slower reaction to yield totally inert enzyme. In addition to the pyruvate kinase activity of the enzyme, modification with 5'-p-fluorosulfonylbenzoyladenosine also disrupts its ability to catalyze the decarboxylation of oxaloacetate and the ATP-dependent enolization of pyruvate. In correspondence with the time dependence of inactivation, the rate of incorporation of 5'-p-[14C]fluorosulfonylbenzoyladenosine is also biphasic. Two moles of reagent per mole of enzyme subunit are bound when the enzyme is completely inactive. The pseudo-first-order rate constant for the rapid rate is linearly dependent on reagent concentration, whereas the constant for the slow rate exhibits saturation kinetics, suggesting that the reagent binds reversibly to the second site prior to modification. The adenosine moiety is essential for the effectiveness of 5'-p-fluorosulfonylbenzoyladenosine, since p-fluorosulfonylbenzoic acid does not inactivate pyruvate kinase at a significant rate. Thus, the reaction of 5'-p-fluorosulfonylbenzoyladenosine with pyruvate kinase exhibits several of the characteristics of affinity labeling of the enzyme. Protection against inactivation by 5'-p-fluorosulfonylbenzoyladenosine is provided by the addition to the incubation mixture of phosphoenolpyruvate. Mg-ADP or Mg2+. In contrast, the addition of pyruvate, Mg-ATP, or ADP and ATP alone has no effect on the rate of inactivation. These observations are consistent with the postulate that the 5'-p-fluorosulfonylbenzoyladenosine specifically labels amino acid residues in the binding region of Mg2+ and the phosphoryl group of phosphoenolpyruvate which is transferred during the catalytic reaction. The rate of inactivation increases with increasing pH, and k1 depends on the unprotonated form of an amino acid residue with pK = 8.5. On the basis of the pH dependence of the reaction of pyruvate kinase with 5'-p-fluorosulfonylbenzoyladenosine and the elimination of cysteine residues as possible sites of reaction, it is postulated that lysyl or tyrosyl residues are the most probably candidates for the critical amino acids."}
{"id": "PMID:14679", "title": "Selective chemical modification of Escherichia coli elongation factor G: butanedione modification of an arginine essential for nucleotide binding.", "content": "Treatment of Escherichia coli elongation factor G with the arginine reagent, 2,3-butanedione, leads to the inactivation of the enzyme when performed in sodium borate buffers. The inhibition follows pseudo-first-order kinetics until 95% of the activity has been lost and further incubation results in complete inhibiton. Removal of the borate by exhaustive dialysis results in the restoration of approximately 85% of the original activity. The pH dependence of the reaction suggests that the ionization of a group in the protein with a pKa of approximately 8.8 facilitates the reaction with butanedione. A reaction order of 1.01 +/- 0.13 was calculated for the inhibition reaction, indicating that the incorporation of one butanedione per elongation factor G results in the inactivation of the enzyme. The kinetics of inhibition in the presence of GTP indicate that the elongation factor G-GTP complex is refractory to butanedione inhibiton. Elongation factor G which has been partially inactivated by butanedione has the same apparent Km for GTP as does the native enzyme. These results indicate that elongation factor G contains only one essential arginine residue which is reactive with butanedione and that this residue is located at its nucleotide binding site.", "contents": "Selective chemical modification of Escherichia coli elongation factor G: butanedione modification of an arginine essential for nucleotide binding. Treatment of Escherichia coli elongation factor G with the arginine reagent, 2,3-butanedione, leads to the inactivation of the enzyme when performed in sodium borate buffers. The inhibition follows pseudo-first-order kinetics until 95% of the activity has been lost and further incubation results in complete inhibiton. Removal of the borate by exhaustive dialysis results in the restoration of approximately 85% of the original activity. The pH dependence of the reaction suggests that the ionization of a group in the protein with a pKa of approximately 8.8 facilitates the reaction with butanedione. A reaction order of 1.01 +/- 0.13 was calculated for the inhibition reaction, indicating that the incorporation of one butanedione per elongation factor G results in the inactivation of the enzyme. The kinetics of inhibition in the presence of GTP indicate that the elongation factor G-GTP complex is refractory to butanedione inhibiton. Elongation factor G which has been partially inactivated by butanedione has the same apparent Km for GTP as does the native enzyme. These results indicate that elongation factor G contains only one essential arginine residue which is reactive with butanedione and that this residue is located at its nucleotide binding site."}
{"id": "PMID:14680", "title": "Light-activated calcium release from sonicated bovine retinal rod outer segment disks.", "content": "Calcium trapped within sonicated and resealed bovine rod outer segment disks is released upon light exposure with a stoichiometry of 0.75 +/- 0.05 calcium for each rhodopsin bleached. The amount of calcium liberated is proportional to the amount of bleaching in the range of 20 to 100% bleaching and is relatively insensitive to the internal trapped calcium concentration. The results are obtained using a flow system in which the disk membrane vesicles are adsorbed on glass particle supported by a filter. The external calcium is washed away and subsequent calcium release is monitored by collecting fractions of the effluent before, during, and after light exposure. Disks that are sonicated and allowed to reseal prior to incubation with 45Ca show no change in calcium efflux upon bleaching. The light-activated calcium release is also eliminated if disks sonicated in the presence of 45Ca are treated with a calcium ionophore prior to bleaching. The results demonstrate that the light-released calcium comes from the disks and not from the external disk surface. Lowering temperature to 3--4 degrees C surpresses the light-stimulated release, implicating a transition after the formation of metarhodopsin I in the transport process. The resluts suggest a model for the disk in which each bleached rhodopsin functions as a \"one-shot carrier\" to transport a single calcium ion across the membrane.", "contents": "Light-activated calcium release from sonicated bovine retinal rod outer segment disks. Calcium trapped within sonicated and resealed bovine rod outer segment disks is released upon light exposure with a stoichiometry of 0.75 +/- 0.05 calcium for each rhodopsin bleached. The amount of calcium liberated is proportional to the amount of bleaching in the range of 20 to 100% bleaching and is relatively insensitive to the internal trapped calcium concentration. The results are obtained using a flow system in which the disk membrane vesicles are adsorbed on glass particle supported by a filter. The external calcium is washed away and subsequent calcium release is monitored by collecting fractions of the effluent before, during, and after light exposure. Disks that are sonicated and allowed to reseal prior to incubation with 45Ca show no change in calcium efflux upon bleaching. The light-activated calcium release is also eliminated if disks sonicated in the presence of 45Ca are treated with a calcium ionophore prior to bleaching. The results demonstrate that the light-released calcium comes from the disks and not from the external disk surface. Lowering temperature to 3--4 degrees C surpresses the light-stimulated release, implicating a transition after the formation of metarhodopsin I in the transport process. The resluts suggest a model for the disk in which each bleached rhodopsin functions as a \"one-shot carrier\" to transport a single calcium ion across the membrane."}
{"id": "PMID:14681", "title": "A proton magnetic resonance study of the conformation of methionine-enkephalin as a function of pH.", "content": "It is found that methionine-enkephalin has at least two different conformations in aqueous solution, one at low and one at high pH. From inspection of titration curves and coupling constant values, it seems reasonable to conclude that these conformations are characterized by a folding so as to bring the two ends of the molecule in close proximity. This behavior parallels that found recently in (CD3)2SO as the solvent. It follows that the Phe-Met region of the molecule constitutes a relatively rigid region, but that the chain possesses flexibility around the first Gly residue. Possible implications of this behavior with respect to the receptor site are discussed.", "contents": "A proton magnetic resonance study of the conformation of methionine-enkephalin as a function of pH. It is found that methionine-enkephalin has at least two different conformations in aqueous solution, one at low and one at high pH. From inspection of titration curves and coupling constant values, it seems reasonable to conclude that these conformations are characterized by a folding so as to bring the two ends of the molecule in close proximity. This behavior parallels that found recently in (CD3)2SO as the solvent. It follows that the Phe-Met region of the molecule constitutes a relatively rigid region, but that the chain possesses flexibility around the first Gly residue. Possible implications of this behavior with respect to the receptor site are discussed."}
{"id": "PMID:14682", "title": "Proton translocation in chloroplasts and its relationship to electron transport between the photosystems.", "content": "Using dark adapted isolated spinach chloroplasts and sequences of brief saturating flashes the correlation of the uptake and release of protons with electron transport from Photosystem II to Photosystem I were studied. The following observations and conclusions are reported: (1) Flash-induced proton uptake shows a weak, damped binary oscillation, with maxima occurring after the 2nd, 4th, etc. flashes. The damping factor is comparable to that observed in the O2 flash yield oscillation and therefore explained by misses in Photosystem II. (2) On the average and after a steady state is reached, each flash (i.e. each reduction of Q) induces the uptake of 2H+ from outside the chloroplasts. (3) Flash induced proton release inside the chloroplast membrane shows a strong damped binary oscillation with maximum release occurring also after the 2nd, 4th, etc. flashes. (4) This phenomenon is correlated with the earlier reported binary oscillations of electron transport [2] and shows that both electrons and protons are transported in pairs between the photosystems. (5) In two sequential flashes 4H+ from the outside of the thylakoid and 2e- from water are accumulated at a binding site B. Subsequently, the two electrons are transferred to non-protonated acceptors in Photosystem I (probably plastocyanin and cytochrome f) and the 4H+ are released inside the thylakoid. (6) It is concluded that a primary proton transporting site and/or energy conserving step located between the photosystems is being observed.", "contents": "Proton translocation in chloroplasts and its relationship to electron transport between the photosystems. Using dark adapted isolated spinach chloroplasts and sequences of brief saturating flashes the correlation of the uptake and release of protons with electron transport from Photosystem II to Photosystem I were studied. The following observations and conclusions are reported: (1) Flash-induced proton uptake shows a weak, damped binary oscillation, with maxima occurring after the 2nd, 4th, etc. flashes. The damping factor is comparable to that observed in the O2 flash yield oscillation and therefore explained by misses in Photosystem II. (2) On the average and after a steady state is reached, each flash (i.e. each reduction of Q) induces the uptake of 2H+ from outside the chloroplasts. (3) Flash induced proton release inside the chloroplast membrane shows a strong damped binary oscillation with maximum release occurring also after the 2nd, 4th, etc. flashes. (4) This phenomenon is correlated with the earlier reported binary oscillations of electron transport [2] and shows that both electrons and protons are transported in pairs between the photosystems. (5) In two sequential flashes 4H+ from the outside of the thylakoid and 2e- from water are accumulated at a binding site B. Subsequently, the two electrons are transferred to non-protonated acceptors in Photosystem I (probably plastocyanin and cytochrome f) and the 4H+ are released inside the thylakoid. (6) It is concluded that a primary proton transporting site and/or energy conserving step located between the photosystems is being observed."}
{"id": "PMID:14683", "title": "Light-depending rubidium transport in intact Halobacterium halobium cells.", "content": "The uptake of rubidium in intact Halobacterium halobium cells was followed, and found to be light-dependent. The exchange process is slow, the steady-state rate of 86Rb+/Rb+ exchange being given by k. = 6.3 - 10(-4) min-1. Starved cells exhibited a faster rate than unstarved cells. The influx of 86Rb+ was almost completely blocked in the presence of proton conductors (CCCP, FCCP, and SF 6847), and was sensitive to the presence of the permeant cation TPMP+. Valinomycin very slightly increased the rate of uptake, while 1 - 10(-6) M nigericin showed significant inhibition. On the other hand, release of 86Rb+ was not light-dependent, although still affected by uncouplers, TPMP+, and nigericin. These experimental observations may be explained in terms of a passive flux driven by an electrical potential difference, and influenced by positive isotope interaction within the membrane. In carefully matched influx-efflux studies, the extent of the positive isotope interaction was measured. Using the formal treatment of Kedem and Essig, the ratio (exchange resistance)/(resistance to net flow) for 86Rb+ was found to be 1.7.", "contents": "Light-depending rubidium transport in intact Halobacterium halobium cells. The uptake of rubidium in intact Halobacterium halobium cells was followed, and found to be light-dependent. The exchange process is slow, the steady-state rate of 86Rb+/Rb+ exchange being given by k. = 6.3 - 10(-4) min-1. Starved cells exhibited a faster rate than unstarved cells. The influx of 86Rb+ was almost completely blocked in the presence of proton conductors (CCCP, FCCP, and SF 6847), and was sensitive to the presence of the permeant cation TPMP+. Valinomycin very slightly increased the rate of uptake, while 1 - 10(-6) M nigericin showed significant inhibition. On the other hand, release of 86Rb+ was not light-dependent, although still affected by uncouplers, TPMP+, and nigericin. These experimental observations may be explained in terms of a passive flux driven by an electrical potential difference, and influenced by positive isotope interaction within the membrane. In carefully matched influx-efflux studies, the extent of the positive isotope interaction was measured. Using the formal treatment of Kedem and Essig, the ratio (exchange resistance)/(resistance to net flow) for 86Rb+ was found to be 1.7."}
{"id": "PMID:14684", "title": "The pH dependence of the oxidation-reduction midpoint potential of cytochromes c2 in vivo.", "content": "A recent report by Pettigrew et al. [Biochim, Biophys. Acta 430, (1976), 197-208] has examined the pH dependence of the oxidation-reduction midpoint potential of cytochromes c2 in vitro. In media of low ionic strength, these workers identified several pKs on the oxidized forms of the cytochromes, and in some cases there were also pKs on the reduced species. In this work we examine the pH dependence of the midpoint potentials of the cytochromes in situ, attached to the chromatophore membrane. Under these conditions no pK values are detected, and we conclude that in vivo there is no net change in the protonation of cytochrome c2 during oxidation or reduction.", "contents": "The pH dependence of the oxidation-reduction midpoint potential of cytochromes c2 in vivo. A recent report by Pettigrew et al. [Biochim, Biophys. Acta 430, (1976), 197-208] has examined the pH dependence of the oxidation-reduction midpoint potential of cytochromes c2 in vitro. In media of low ionic strength, these workers identified several pKs on the oxidized forms of the cytochromes, and in some cases there were also pKs on the reduced species. In this work we examine the pH dependence of the midpoint potentials of the cytochromes in situ, attached to the chromatophore membrane. Under these conditions no pK values are detected, and we conclude that in vivo there is no net change in the protonation of cytochrome c2 during oxidation or reduction."}
{"id": "PMID:14685", "title": "Acetylation of histones in isolated avian erythroid nuclei.", "content": "1. Suspensions of avian erythroid nuclei, of high purity, were prepared. Acetylation of histones was observed when nuclei were incubated in the presence of [1-14C]acetyl CoA, but not in the presence of sodium [3H]acetate. 2. The acetylation reaction was very heat labile and reproduced the in vivo reaction with high fidelity. The reaction was strongly inhibited by divalent cations and cysteine. 3. Studies, in which intact cells were pre-incubated with cycloheximide prior to the isolation of nuclei, suggested that histone acetylation in isolated erythroid nuclei was largely independent of histone synthesis. 4. The pH profile suggested the presence of at least two histone acetyltransferases, with pH optima at 8.0 and 8.6. Acetylation of histone H4 appeared to be favoured at pH 8.0. 5. Studies on histone acetylation in isolated nuclei should be very useful in correlating observations on histone acetylation in vivo, with experiments using purified histone acetyltransferases.", "contents": "Acetylation of histones in isolated avian erythroid nuclei. 1. Suspensions of avian erythroid nuclei, of high purity, were prepared. Acetylation of histones was observed when nuclei were incubated in the presence of [1-14C]acetyl CoA, but not in the presence of sodium [3H]acetate. 2. The acetylation reaction was very heat labile and reproduced the in vivo reaction with high fidelity. The reaction was strongly inhibited by divalent cations and cysteine. 3. Studies, in which intact cells were pre-incubated with cycloheximide prior to the isolation of nuclei, suggested that histone acetylation in isolated erythroid nuclei was largely independent of histone synthesis. 4. The pH profile suggested the presence of at least two histone acetyltransferases, with pH optima at 8.0 and 8.6. Acetylation of histone H4 appeared to be favoured at pH 8.0. 5. Studies on histone acetylation in isolated nuclei should be very useful in correlating observations on histone acetylation in vivo, with experiments using purified histone acetyltransferases."}
{"id": "PMID:14686", "title": "Separation of DNA-dependent DNA polymerase activities in Micrococcus radiodurans.", "content": "DNA polymerase activities in Micrococcus radiodurans were separated into two fractions after purification more than 2000 fold. They differ in pH optimum and residual activities in the absence of a full deoxyribonucleoside triphosphates complement. NAD partly inhibited one of the activities. Both activities were eluted as a single peak on gel filtration and sedimented at the same rate on glycerol gradient centrifugation. Molecular weight 140000 was calculated from Stokes radius and sedimentation constant. Deoxyribonuclease activity was detected on one of the polymerase activities which preferentially degraded double-stranded DNA. Priming activity of nicked DNA was reduced by gamma-irradiation. These results have been related to the possible rolls in repair synthesis in vivo or DNA synthesis in permeable cells of M. radiodurans.", "contents": "Separation of DNA-dependent DNA polymerase activities in Micrococcus radiodurans. DNA polymerase activities in Micrococcus radiodurans were separated into two fractions after purification more than 2000 fold. They differ in pH optimum and residual activities in the absence of a full deoxyribonucleoside triphosphates complement. NAD partly inhibited one of the activities. Both activities were eluted as a single peak on gel filtration and sedimented at the same rate on glycerol gradient centrifugation. Molecular weight 140000 was calculated from Stokes radius and sedimentation constant. Deoxyribonuclease activity was detected on one of the polymerase activities which preferentially degraded double-stranded DNA. Priming activity of nicked DNA was reduced by gamma-irradiation. These results have been related to the possible rolls in repair synthesis in vivo or DNA synthesis in permeable cells of M. radiodurans."}
{"id": "PMID:14687", "title": "Iodination-deiodination. A radiochemical method for detection of structure and changes in structure in RNA.", "content": "Bound iodine is released from radioiodinated nucleotides in polymers exposed to sodium bisulfite. The rate of bisulfite-catalyzed deiodination of pyrimidines can be controlled both by change of temperature of pH and is also dependent on the molecular association of the nucleotide. The rate of release of iodine from iodocytidine in polycytidylate is greater than the rate of elimination from RNA. Experiments testing the influence of base-pairing of the iodopyrimidines in synthetic polynucleotides showed that pairing of the substituted nucleotide protected the iodine bond. The rates of bisulfite-catalyzed deiodination of several radioiodinated RNAs were measured. The action of bisulfite on all single stranded RNAs tested was multiphasic consisting of a rapid early deiodination reaction supplanted by a slower phase which was followed by reacceleration of release. The release of iodine from double stranded RNA and DNA-RNA duplexes was retarded in comparison with the release from ribosomal and messenger RNA fractions. The deiodination profiles of single and double stranded RNA suggested that the intermediate stage iodine release is governed by melting of paired zones of low stability. Late release may result from destablization of the molecule through the addition of bisulfite to the pyrimidine ring or deamination. The effect of several substances expected to complex with polynucleotides was tested. Acridine orange and ethidium bromide increased loss of iodine from ribosomal RNA but slightly decreased elimination from double stranded viral RNA. A basic protein fraction isolated from ribosomal particles accelerated the deiodination of ribosomal RNA. While the destabilization caused by this protein fraction was greater than that caused by an equal amount of albumin, as tested the effect was non-specific. The results show that a change in sensitivity to chemical deiodination may folow the interaction of small amounts of protein with polynucleotides.", "contents": "Iodination-deiodination. A radiochemical method for detection of structure and changes in structure in RNA. Bound iodine is released from radioiodinated nucleotides in polymers exposed to sodium bisulfite. The rate of bisulfite-catalyzed deiodination of pyrimidines can be controlled both by change of temperature of pH and is also dependent on the molecular association of the nucleotide. The rate of release of iodine from iodocytidine in polycytidylate is greater than the rate of elimination from RNA. Experiments testing the influence of base-pairing of the iodopyrimidines in synthetic polynucleotides showed that pairing of the substituted nucleotide protected the iodine bond. The rates of bisulfite-catalyzed deiodination of several radioiodinated RNAs were measured. The action of bisulfite on all single stranded RNAs tested was multiphasic consisting of a rapid early deiodination reaction supplanted by a slower phase which was followed by reacceleration of release. The release of iodine from double stranded RNA and DNA-RNA duplexes was retarded in comparison with the release from ribosomal and messenger RNA fractions. The deiodination profiles of single and double stranded RNA suggested that the intermediate stage iodine release is governed by melting of paired zones of low stability. Late release may result from destablization of the molecule through the addition of bisulfite to the pyrimidine ring or deamination. The effect of several substances expected to complex with polynucleotides was tested. Acridine orange and ethidium bromide increased loss of iodine from ribosomal RNA but slightly decreased elimination from double stranded viral RNA. A basic protein fraction isolated from ribosomal particles accelerated the deiodination of ribosomal RNA. While the destabilization caused by this protein fraction was greater than that caused by an equal amount of albumin, as tested the effect was non-specific. The results show that a change in sensitivity to chemical deiodination may folow the interaction of small amounts of protein with polynucleotides."}
{"id": "PMID:14688", "title": "The effect of monovalent and divalent cations on the activity of Streptococcus lactis C10 pyruvate kinase.", "content": "The pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from Streptococcus lactis C10 had an obligatory requirement for both a monovalent cation and divalent cation. NH+4 and K+ activated the enzyme in a sigmoidal manner (nH =1.55) at similar concentrations, whereas Na+ and Li+ could only weakly activate the enzyme. Of eight divalent cations studied, only three (Co2+, Mg2+ and Mn2+) activated the enzyme. The remaining five divalent cations (Cu2+, Zn2+, Ca2+, Ni2+ and Ba2+) inhibited the Mg2+ activated enzyme to varying degrees. (Cu2+ completely inhibited activity at 0.1 mM while Ba2+, the least potent inhibitor, caused 50% inhibition at 3.2 mM). In the presence of 1 mM fructose 1,6-diphosphate (Fru-1,6-P2) the enzyme showed a different kinetic response to each of the three activating divalent cations. For Co2+, Mn2+ and Mg2+ the Hill interaction coefficients (nH) were 1.6, 1.7 and 2.3 respectively and the respective divalent cation concentrations required for 50% maximum activity were 0.9, 0.46 and 0.9 mM. Only with Mn2+ as the divalent cation was there significatn activity in the absence of Fru-1,6-P2. When Mn2+ replaced Mg2+, the Fru-1,6-P2 activation changed from sigmoidal (nH = 2.0) to hyperbolic (nH = 1.0) kinetics and the Fru-1,6-P2 concentration required for 50% maximum activity decreased from 0.35 to 0.015 mM. The cooperativity of phosphoenolpyruvate binding increased (nH 1.2 to 1.8) and the value of the phosphoenolpyruvate concentration giving half maximal velocity decreased (0.18 to 0.015 mM phosphoenolyruvate) when Mg2+ was replaced by Mn2+ in the presence of 1 mM Fru-1,6-P2. The kinetic response to ADP was not altered significantly when Mn2+ was substituted for Mg2+. The effects of pH on the binding of phosphoenolpyruvate and Fru-1,6-P2 were different depending on whether Mg2+ or Mn2+ was the divalent cation.", "contents": "The effect of monovalent and divalent cations on the activity of Streptococcus lactis C10 pyruvate kinase. The pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from Streptococcus lactis C10 had an obligatory requirement for both a monovalent cation and divalent cation. NH+4 and K+ activated the enzyme in a sigmoidal manner (nH =1.55) at similar concentrations, whereas Na+ and Li+ could only weakly activate the enzyme. Of eight divalent cations studied, only three (Co2+, Mg2+ and Mn2+) activated the enzyme. The remaining five divalent cations (Cu2+, Zn2+, Ca2+, Ni2+ and Ba2+) inhibited the Mg2+ activated enzyme to varying degrees. (Cu2+ completely inhibited activity at 0.1 mM while Ba2+, the least potent inhibitor, caused 50% inhibition at 3.2 mM). In the presence of 1 mM fructose 1,6-diphosphate (Fru-1,6-P2) the enzyme showed a different kinetic response to each of the three activating divalent cations. For Co2+, Mn2+ and Mg2+ the Hill interaction coefficients (nH) were 1.6, 1.7 and 2.3 respectively and the respective divalent cation concentrations required for 50% maximum activity were 0.9, 0.46 and 0.9 mM. Only with Mn2+ as the divalent cation was there significatn activity in the absence of Fru-1,6-P2. When Mn2+ replaced Mg2+, the Fru-1,6-P2 activation changed from sigmoidal (nH = 2.0) to hyperbolic (nH = 1.0) kinetics and the Fru-1,6-P2 concentration required for 50% maximum activity decreased from 0.35 to 0.015 mM. The cooperativity of phosphoenolpyruvate binding increased (nH 1.2 to 1.8) and the value of the phosphoenolpyruvate concentration giving half maximal velocity decreased (0.18 to 0.015 mM phosphoenolyruvate) when Mg2+ was replaced by Mn2+ in the presence of 1 mM Fru-1,6-P2. The kinetic response to ADP was not altered significantly when Mn2+ was substituted for Mg2+. The effects of pH on the binding of phosphoenolpyruvate and Fru-1,6-P2 were different depending on whether Mg2+ or Mn2+ was the divalent cation."}
{"id": "PMID:14689", "title": "Cyclic nucleotide phosphodiesterases of Hyalophora cecropia silkmoth fat body.", "content": "Two soluble forms of 3':5'-cyclic-nucleotide phosphodiesterase (o':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) were found in the larval fat body of the silkmoth Hyalophora cecropia. These differ in elution profile on Sephadex G-200, solubility in ammonium sulfate, metal ion requirements and kinetic properties. Phosphodiesterase I has Km values of 11 muM and 1.8 muM for cyclic AMP and cyclic GMP, respectively, has 5-fold greater maximal activity with cyclic AMP than with cyclic GMP, and is activated by Mg2+ and Co2+, and inhibited by EDTA. phosphodiesterase II has Km values of 625 muM and 125 muM for cyclic AMP and cyclic GMP, respectively, has similar maximal activity with both substrates, and is not activated by divalent metal ions or inhibited by EDTA. Cyclic nucleotides and methylxanthines competitively inhibit both enzymes. Phosphodiesterase is found in both soluble and particulate fractions of homogenates. Total activity is highest during the larval stage of the insect, drops markedly following pupation, and rises again during pharate adult development.", "contents": "Cyclic nucleotide phosphodiesterases of Hyalophora cecropia silkmoth fat body. Two soluble forms of 3':5'-cyclic-nucleotide phosphodiesterase (o':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) were found in the larval fat body of the silkmoth Hyalophora cecropia. These differ in elution profile on Sephadex G-200, solubility in ammonium sulfate, metal ion requirements and kinetic properties. Phosphodiesterase I has Km values of 11 muM and 1.8 muM for cyclic AMP and cyclic GMP, respectively, has 5-fold greater maximal activity with cyclic AMP than with cyclic GMP, and is activated by Mg2+ and Co2+, and inhibited by EDTA. phosphodiesterase II has Km values of 625 muM and 125 muM for cyclic AMP and cyclic GMP, respectively, has similar maximal activity with both substrates, and is not activated by divalent metal ions or inhibited by EDTA. Cyclic nucleotides and methylxanthines competitively inhibit both enzymes. Phosphodiesterase is found in both soluble and particulate fractions of homogenates. Total activity is highest during the larval stage of the insect, drops markedly following pupation, and rises again during pharate adult development."}
{"id": "PMID:14690", "title": "Influence of pH and sodium on the inhibition of guinea-pig heart (Na+ + K+)-ATPase by calcium.", "content": "The inhibition of guinea-pig heart (Na+ + K+)-ATPase (ATP phosphohydrolase EC 3.6.1.3) by calcium has been studied at pH 7.4, 6.8 and 6.4. 1. A decrease in pH reduced the threshold inhibitory concentration of calcium and the calcium concentration producing an inhibition of 50% of the enzyme activity. 2. Calcium reduced the apparent affinity of the enzyme of Na+, this effect occurred only at pH 7.4. 3. Calcium increased the apparent affinity of the enzyme for K+, this effect was enhanced at acidic pH. 4. Activation of the enzyme by Na+ for a constant Na+ : K+ ratio has been studied at pH 7.4 and at pH 6.8 in the absence and in the presence of 3.10(-4) M Ca 2+; the results of this experiment indicate that Ca2+ effect at pH 7.4 was not influenced by Na+ -- K+ competition and was probably due to a Na+ -- Ca2+ interaction. 5. At pH 7.4, the calcium inhibitory threshold concentration and the concentration producing 50% inhibition were reduced when Na+ was low; at pH 6.8, the calcium inhibition was not markedly modified by the change of Na+ concentration. 6. The Ca2+ -activated ATPase of myosin B which is related to the contractile behaviour of muscle and the Ca2+  -ATPase of the sarcoplasmic reticulum which is related to the ability of this structure to accumulate calcium were activated in a range of calcium concentration producing an inhibition of (Na2+ + K+) -ATPase. The present results indicate that the increase by acidity of the (Na2+ + K+) -ATPase sensitivity to calcium might be due to a suppression of a Na+ -Ca2+ interaction. On the basis of these observations, it is proposed that calcium might inhibit the Na+ -pump during the repolarization phase of the action potential and that, by this effect, it might control cell excitability.", "contents": "Influence of pH and sodium on the inhibition of guinea-pig heart (Na+ + K+)-ATPase by calcium. The inhibition of guinea-pig heart (Na+ + K+)-ATPase (ATP phosphohydrolase EC 3.6.1.3) by calcium has been studied at pH 7.4, 6.8 and 6.4. 1. A decrease in pH reduced the threshold inhibitory concentration of calcium and the calcium concentration producing an inhibition of 50% of the enzyme activity. 2. Calcium reduced the apparent affinity of the enzyme of Na+, this effect occurred only at pH 7.4. 3. Calcium increased the apparent affinity of the enzyme for K+, this effect was enhanced at acidic pH. 4. Activation of the enzyme by Na+ for a constant Na+ : K+ ratio has been studied at pH 7.4 and at pH 6.8 in the absence and in the presence of 3.10(-4) M Ca 2+; the results of this experiment indicate that Ca2+ effect at pH 7.4 was not influenced by Na+ -- K+ competition and was probably due to a Na+ -- Ca2+ interaction. 5. At pH 7.4, the calcium inhibitory threshold concentration and the concentration producing 50% inhibition were reduced when Na+ was low; at pH 6.8, the calcium inhibition was not markedly modified by the change of Na+ concentration. 6. The Ca2+ -activated ATPase of myosin B which is related to the contractile behaviour of muscle and the Ca2+  -ATPase of the sarcoplasmic reticulum which is related to the ability of this structure to accumulate calcium were activated in a range of calcium concentration producing an inhibition of (Na2+ + K+) -ATPase. The present results indicate that the increase by acidity of the (Na2+ + K+) -ATPase sensitivity to calcium might be due to a suppression of a Na+ -Ca2+ interaction. On the basis of these observations, it is proposed that calcium might inhibit the Na+ -pump during the repolarization phase of the action potential and that, by this effect, it might control cell excitability."}
{"id": "PMID:14691", "title": "Mn2+-sensitive, soluble adenylate cyclase in rat testis. Differentiation from other testicular nucleotide cyclases.", "content": "In subcellular fractions prepared from homogenate of adult rat testis adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity was found in the particulate, primarily 600 X g for 10 min, fractions, as well as in the cytosol. The properties of the adenylate cyclase in the cytosol differs substantially from the adenylate cyclase system associated with the 600 X g for 10 min particulate fraction. The cytosol enzyme, in contrast to the particulate adenylate cyclase, was found to be fluoride- and gonadotropin hormone-insensitive. The cytosol adenylate cyclase appears to be located in the germ cell while the particulate enzyme system in the non-germ cell component of the seminiferous tubules, The cytosol adenylate cyclase was found to be distinct also from the guanylate cyclase present in the rat testis cytosol. The adenylate cyclase appears to be located in the germ cell component while the guanylate cyclase, in the non-germ cell tubular component. Furthermore, it was found that the cytosol guanylate cyclase develops at an earlier stage of spermatogenesis, and precedes the development of the cytosol adenylate cyclase.", "contents": "Mn2+-sensitive, soluble adenylate cyclase in rat testis. Differentiation from other testicular nucleotide cyclases. In subcellular fractions prepared from homogenate of adult rat testis adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity was found in the particulate, primarily 600 X g for 10 min, fractions, as well as in the cytosol. The properties of the adenylate cyclase in the cytosol differs substantially from the adenylate cyclase system associated with the 600 X g for 10 min particulate fraction. The cytosol enzyme, in contrast to the particulate adenylate cyclase, was found to be fluoride- and gonadotropin hormone-insensitive. The cytosol adenylate cyclase appears to be located in the germ cell while the particulate enzyme system in the non-germ cell component of the seminiferous tubules, The cytosol adenylate cyclase was found to be distinct also from the guanylate cyclase present in the rat testis cytosol. The adenylate cyclase appears to be located in the germ cell component while the guanylate cyclase, in the non-germ cell tubular component. Furthermore, it was found that the cytosol guanylate cyclase develops at an earlier stage of spermatogenesis, and precedes the development of the cytosol adenylate cyclase."}
{"id": "PMID:14692", "title": "Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of serine transacetylase, O-acetylserine sulphydrylase and beta-cystathionase.", "content": "1. Serine transacetylase, O-acetylserine sulphydrylase and beta-cystathionase were purified from Paracoccus denitrificans strain 8944. 2. Serin transacetylase was purified 150-fold. The enzyme has a pH optimum between 7.5 and 8.0, is specific for L-serine and is inhibited by sulphydryl-group reagents. The apparent Km values for serine and acetyl-CoA are 4.0 - 10(-4) and 1.0 - 10(-4) M, respectively. Serine transacetylase is strongly inhibited by cysteine. 3. O-Acetylserine sulphydrylase was purified 450-fold. The enzymes has a sharp pH optimum at pH 7.5. In addition to catalysing the synthesis of cysteine, O-acetylserine sulphydrylase catalyses the synthesis of selenocysteine from O-acetylserine and selenide. The Km values for sulphide and O-acetylserine are 2.7 - 10(-3) and 1.25 - 10(-3) M, respectively. The enzyme was stimulated by pyridoxal phosphate and was inhibited by cystathionine, homocysteine and methionine. 4. beta-Cystathionase was purified approx. 50-fold. beta-Cystathionase has a pH optimum between pH 9.0 and 9.5, is sensitive to sulphydryl-group reagents, required pyridoxal phosphate for maximum activity and has an apparent Km for cystathionine of 4.2 - 10 (-3) M. beta-Cystathionase also catalyses the release of keto acid from lanthionine, djenkolic acid and cystine. Cysteine, O-acetylserine, homocysteine and glutathione strongly inhibit beta-cystathionase activity and homocysteine and methionine represses enzyme activity. 5. O-Acetylserine lyase was identified in crude extracts of Paracoccus denitrificans. The enzyme is specific  for O-acetyl-L-serine, requires pyridoxal phosphate and is inhibied by KCN and hydroxylamine. The enzyme has a high Km value for O-acetylserine (50--100 mM).", "contents": "Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of serine transacetylase, O-acetylserine sulphydrylase and beta-cystathionase. 1. Serine transacetylase, O-acetylserine sulphydrylase and beta-cystathionase were purified from Paracoccus denitrificans strain 8944. 2. Serin transacetylase was purified 150-fold. The enzyme has a pH optimum between 7.5 and 8.0, is specific for L-serine and is inhibited by sulphydryl-group reagents. The apparent Km values for serine and acetyl-CoA are 4.0 - 10(-4) and 1.0 - 10(-4) M, respectively. Serine transacetylase is strongly inhibited by cysteine. 3. O-Acetylserine sulphydrylase was purified 450-fold. The enzymes has a sharp pH optimum at pH 7.5. In addition to catalysing the synthesis of cysteine, O-acetylserine sulphydrylase catalyses the synthesis of selenocysteine from O-acetylserine and selenide. The Km values for sulphide and O-acetylserine are 2.7 - 10(-3) and 1.25 - 10(-3) M, respectively. The enzyme was stimulated by pyridoxal phosphate and was inhibited by cystathionine, homocysteine and methionine. 4. beta-Cystathionase was purified approx. 50-fold. beta-Cystathionase has a pH optimum between pH 9.0 and 9.5, is sensitive to sulphydryl-group reagents, required pyridoxal phosphate for maximum activity and has an apparent Km for cystathionine of 4.2 - 10 (-3) M. beta-Cystathionase also catalyses the release of keto acid from lanthionine, djenkolic acid and cystine. Cysteine, O-acetylserine, homocysteine and glutathione strongly inhibit beta-cystathionase activity and homocysteine and methionine represses enzyme activity. 5. O-Acetylserine lyase was identified in crude extracts of Paracoccus denitrificans. The enzyme is specific  for O-acetyl-L-serine, requires pyridoxal phosphate and is inhibied by KCN and hydroxylamine. The enzyme has a high Km value for O-acetylserine (50--100 mM)."}
{"id": "PMID:14693", "title": "Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of cysteinyl-and methionyl-tRNA synthetase.", "content": "Cysteinyl- and methionyl-tRNA synthetases (EC 6.11.-) were purified 1200- and 1000-fold, respectively, from sonic extracts of Paracoccus denitrificans strain 8944, and kinetics, substrate specificity and regulatory properties were determined using the ATP-PPi exchange reaction. Both enzymes had pH optima of approx. 8 and were inhibited by sulphydryl-group reagents. Cysteinyl-tRNA synthetase catalysed L-selenocysteine- and alpha-aminobutyric acid-dependent ATP-PPi exchange and methionyl-tRNA synthetase catalysed L-homocysteine-, L-selenomethionine- and norleucine-dependent ATP-PPi exchange. Both enzymes were inhibited by O-acetylserine. Cysteinyl-tRNA synthetase activity was stimulated by methionine and methionyl-tRNA synthetase activity was stimulated by sulphide, cysteine, and cysteic acid.", "contents": "Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of cysteinyl-and methionyl-tRNA synthetase. Cysteinyl- and methionyl-tRNA synthetases (EC 6.11.-) were purified 1200- and 1000-fold, respectively, from sonic extracts of Paracoccus denitrificans strain 8944, and kinetics, substrate specificity and regulatory properties were determined using the ATP-PPi exchange reaction. Both enzymes had pH optima of approx. 8 and were inhibited by sulphydryl-group reagents. Cysteinyl-tRNA synthetase catalysed L-selenocysteine- and alpha-aminobutyric acid-dependent ATP-PPi exchange and methionyl-tRNA synthetase catalysed L-homocysteine-, L-selenomethionine- and norleucine-dependent ATP-PPi exchange. Both enzymes were inhibited by O-acetylserine. Cysteinyl-tRNA synthetase activity was stimulated by methionine and methionyl-tRNA synthetase activity was stimulated by sulphide, cysteine, and cysteic acid."}
{"id": "PMID:14694", "title": "The rate of reaction between cytochrome C peroxidase and hydrogen peroxide is not diffusion limited.", "content": "The apparent biomolecular rate constant for the cytochrome C peroxidase (EC 1.11.1.5)-hydrogen peroxide reaction has been measured as a function of temperature between 5 and 25 degree C at pH 4,5.5, and 7 and as a function of viscosity over a fifteen-fold range. From the independence of the rate constant on the viscosity, it is concluded that the reaction is not diffusion limited.", "contents": "The rate of reaction between cytochrome C peroxidase and hydrogen peroxide is not diffusion limited. The apparent biomolecular rate constant for the cytochrome C peroxidase (EC 1.11.1.5)-hydrogen peroxide reaction has been measured as a function of temperature between 5 and 25 degree C at pH 4,5.5, and 7 and as a function of viscosity over a fifteen-fold range. From the independence of the rate constant on the viscosity, it is concluded that the reaction is not diffusion limited."}
{"id": "PMID:14695", "title": "L-glycerol-3-phosphate dehydrogenase from the insect Ceratitis capitata. Purfication, physicochemical and enzymic properties.", "content": "Soluble L-glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8) from the mediterranean fruit fly Ceratitis capitata has been purified 130-fold with an overall yield of about 40%. The final preparation had a specific activity of about 200 mumol NADH/min/mg protein. The enzyme preparation has been shown to be homogeneous throughout disc gel electrophoresis, dodecyl sulphate gel electrophoresis, isoelectric focusing and ultracentrifugation. The Km values for dihydroxyacetone phosphate, NADH, L-glycerol-3-phosphate and NAD+ were respectively 0.33, 0.018, 0.74 and 0.26 mM. L-glycerol-3-phosphate dehydrogenase from the insect had a maximal activity around pH 6.6 for the oxidation of NADH and pH 10.0 for the reduction of NAD+. It was stable from pH 6.0 to pH 9.0 at 20 degrees C for 1 h and remained active after incubating at 30 degrees C for 30 min at pH 6.6. The enzyme was completely inactivated by incubating at 60 degrees C for 5 min. Enzyme stability versus ionic strength as well as the dependence of the reaction velocity on temperature are also reported. The active enzyme was found to have a minimum molecular weight of approx. 63 000. Molecular weight determinations by sodium dodecyl sulphate gel electrophoresis gave subunit weights of 33 500. The isoelectric point of the protein was determined by electrofocusing and found to be 5.75 +/- 0.05. The extinction coefficient at 278 nm was calculated by dry weight measurements to be E1cm 1mg/ml = 0.42 +/- 0.1. Sedimentation velocity studies on ultracentrifuge indicated a dependence of the sedimentation coefficient on the enzyme concentration. The amino acid composition of the enzyme was determined. The protein has no free N-terminal residue and the digestion with carboxypeptidases gave the C-terminal sequence: -ala-gly-ser. All these data are discussed in relation to the properties of the enzyme from other sources.", "contents": "L-glycerol-3-phosphate dehydrogenase from the insect Ceratitis capitata. Purfication, physicochemical and enzymic properties. Soluble L-glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8) from the mediterranean fruit fly Ceratitis capitata has been purified 130-fold with an overall yield of about 40%. The final preparation had a specific activity of about 200 mumol NADH/min/mg protein. The enzyme preparation has been shown to be homogeneous throughout disc gel electrophoresis, dodecyl sulphate gel electrophoresis, isoelectric focusing and ultracentrifugation. The Km values for dihydroxyacetone phosphate, NADH, L-glycerol-3-phosphate and NAD+ were respectively 0.33, 0.018, 0.74 and 0.26 mM. L-glycerol-3-phosphate dehydrogenase from the insect had a maximal activity around pH 6.6 for the oxidation of NADH and pH 10.0 for the reduction of NAD+. It was stable from pH 6.0 to pH 9.0 at 20 degrees C for 1 h and remained active after incubating at 30 degrees C for 30 min at pH 6.6. The enzyme was completely inactivated by incubating at 60 degrees C for 5 min. Enzyme stability versus ionic strength as well as the dependence of the reaction velocity on temperature are also reported. The active enzyme was found to have a minimum molecular weight of approx. 63 000. Molecular weight determinations by sodium dodecyl sulphate gel electrophoresis gave subunit weights of 33 500. The isoelectric point of the protein was determined by electrofocusing and found to be 5.75 +/- 0.05. The extinction coefficient at 278 nm was calculated by dry weight measurements to be E1cm 1mg/ml = 0.42 +/- 0.1. Sedimentation velocity studies on ultracentrifuge indicated a dependence of the sedimentation coefficient on the enzyme concentration. The amino acid composition of the enzyme was determined. The protein has no free N-terminal residue and the digestion with carboxypeptidases gave the C-terminal sequence: -ala-gly-ser. All these data are discussed in relation to the properties of the enzyme from other sources."}
{"id": "PMID:14696", "title": "Presence and properties of thymidylate synthase in trypanosomatids.", "content": "High speed centrifugal supernatant fractions of homogenates of a number of trypanosomatids were assayed for thymidylate synthase (5,10-methylene-tetrahydrofolate: dUMP C-methyltransferase, EC 2.1.1.45) activity using the method of Lomax and Greenberg (1967) J. Biol. Chem. 242, 109-113). Similar activities were detected in Crithidia fasciculata, Crithidia oncopelti, the blood forms of Trypanosoma brucei, Trypansoma congolense and Trypanosoma lewisi and the blood, intracellular and culture forms of Trypanosoma cruzi, suggesting that all species synthesize at least some thymidylate de novo. The properties of the activities in C. fasciculata and the three forms of T. cruzi were compared with those of the isofunctional bacterial and mammalian enzymes. The trypanosotamid enzyme was inhibited by Mg2+, was much more sensitive to mercaptoethanol, had higher apparent Km values for substrate (dUMP) and cofactor (tetrahydrofolate), had a higher apparent molecular weight and was markedly more sensitive to inhibition by suramin. It is, therefore a possible target for chemotherapeutic attack, either on its own or in combination with a dihydrofolate reductase inhibitor. No evidence was obtained for the regulation of the trypanosomatid enzyme, either by its product, dTMP, or by dTDP or dTTp. This result agrees with previous studies which suggested that in trypanosomatids, the level of dTMP was regulated, at least in part, by a catabolic pathway consisting of a thymidylate phosphatase and a thymidine phosphorylase which degraded the excess of dTMP to thymine.", "contents": "Presence and properties of thymidylate synthase in trypanosomatids. High speed centrifugal supernatant fractions of homogenates of a number of trypanosomatids were assayed for thymidylate synthase (5,10-methylene-tetrahydrofolate: dUMP C-methyltransferase, EC 2.1.1.45) activity using the method of Lomax and Greenberg (1967) J. Biol. Chem. 242, 109-113). Similar activities were detected in Crithidia fasciculata, Crithidia oncopelti, the blood forms of Trypanosoma brucei, Trypansoma congolense and Trypanosoma lewisi and the blood, intracellular and culture forms of Trypanosoma cruzi, suggesting that all species synthesize at least some thymidylate de novo. The properties of the activities in C. fasciculata and the three forms of T. cruzi were compared with those of the isofunctional bacterial and mammalian enzymes. The trypanosotamid enzyme was inhibited by Mg2+, was much more sensitive to mercaptoethanol, had higher apparent Km values for substrate (dUMP) and cofactor (tetrahydrofolate), had a higher apparent molecular weight and was markedly more sensitive to inhibition by suramin. It is, therefore a possible target for chemotherapeutic attack, either on its own or in combination with a dihydrofolate reductase inhibitor. No evidence was obtained for the regulation of the trypanosomatid enzyme, either by its product, dTMP, or by dTDP or dTTp. This result agrees with previous studies which suggested that in trypanosomatids, the level of dTMP was regulated, at least in part, by a catabolic pathway consisting of a thymidylate phosphatase and a thymidine phosphorylase which degraded the excess of dTMP to thymine."}
{"id": "PMID:14697", "title": "A microacalorimetric study of the interaction between trypsin and sodium n-dodecyl sulphate.", "content": "1. The binding of sodium n-dodecyl sulphate to trypsin and reduced trypsin has been measured by equilibrium dialysis at pH 3.5 and 5.5. 2. At pH 3.5 trypsin specifically binds surfactant at low concentration, at higher concentrations co-operative binding occurs. 3. Reduction of trypsin destroys the specific binding sites at pH 3.5. 4. At pH 5.5 both trypsin and reduced trypsin show only co-operative binding. 5. The interaction of sodium n-dodecyl sulphate with trypsin, reduced, inhibited, and thermally denatured trypsins has been studied by microcalorimetry at 25 degrees C. 6. The microcalorimetric measurements have been used to estimate enthalpy changes (deltaHd) on unfolding of trypsin; deltaHd = 82 +/- 5 kJ-mol-1 at pH 3.5 and 128 +/- 5 kJ-mol-1 at pH 5.5. 7. The unfolding of trypsin follows a different thermochemical pathway to that of reduced trypsin.", "contents": "A microacalorimetric study of the interaction between trypsin and sodium n-dodecyl sulphate. 1. The binding of sodium n-dodecyl sulphate to trypsin and reduced trypsin has been measured by equilibrium dialysis at pH 3.5 and 5.5. 2. At pH 3.5 trypsin specifically binds surfactant at low concentration, at higher concentrations co-operative binding occurs. 3. Reduction of trypsin destroys the specific binding sites at pH 3.5. 4. At pH 5.5 both trypsin and reduced trypsin show only co-operative binding. 5. The interaction of sodium n-dodecyl sulphate with trypsin, reduced, inhibited, and thermally denatured trypsins has been studied by microcalorimetry at 25 degrees C. 6. The microcalorimetric measurements have been used to estimate enthalpy changes (deltaHd) on unfolding of trypsin; deltaHd = 82 +/- 5 kJ-mol-1 at pH 3.5 and 128 +/- 5 kJ-mol-1 at pH 5.5. 7. The unfolding of trypsin follows a different thermochemical pathway to that of reduced trypsin."}
{"id": "PMID:14699", "title": "Modification of amino acids and bovine pancreatic ribonuclease A by kethoxal.", "content": "Kethoxal (3-ethoxy-2-ketobutanal) reacts with the guanidino group of Nalpha-acetylarginine to produce four derivatives, reactive to periodate, stable at pH 7, with 15% reverting to arginine on acid hydrolysis. Other amino acids with blocked alpha-amino groups do not react, except the epsilon-amino of lysine (slowly). The pK of the mixed Kethoxal-Nalpha-acetylarginine derivatives is 5.8-6.1. Kethoxal reacts at neutral pH with arginyl residues of bovine pancreatic ribonuclease A. In the presence of an active-site ligand, arginine-39 and arginine-85 react at about equal rates. The loss of enzymic activity at pH 7 is proportional to the combined loss of these residues. The enzymic activity toward RNA is 20-25% of that of native RNAase at pH 7, and 90-100% at pH 5. In the absence of an active site ligand, arginine-10 is also modified with the loss of almost all enzymic activity, although arginine-10 is not an active-site residue. Arginine-33 is unreactive. Kethoxal-modified RNAase undergoes cross-linking in solution at pH 7 or in the freeze-dried state, Incubation at pH 9 in the presence of homoarginine results in partial regeneration of arginyl residues and activity at pH 7. Kethoxal modification of arginines-39 and -85 appears to raise the pK of lysine-41 by about 1 unit, as indicated ty the pH dependence of arylation by 2-carboxy-4,6-dinitrochlorobenzene. The claims of Patthy and Smith (J. Biol, Chem. (1975) 250, 565-569), and of Takahashi (J. Biol. Chem. (1968) 243, 6171-6179) that arginine-39 is a more important functional residue than is arginine-85 are questioned.", "contents": "Modification of amino acids and bovine pancreatic ribonuclease A by kethoxal. Kethoxal (3-ethoxy-2-ketobutanal) reacts with the guanidino group of Nalpha-acetylarginine to produce four derivatives, reactive to periodate, stable at pH 7, with 15% reverting to arginine on acid hydrolysis. Other amino acids with blocked alpha-amino groups do not react, except the epsilon-amino of lysine (slowly). The pK of the mixed Kethoxal-Nalpha-acetylarginine derivatives is 5.8-6.1. Kethoxal reacts at neutral pH with arginyl residues of bovine pancreatic ribonuclease A. In the presence of an active-site ligand, arginine-39 and arginine-85 react at about equal rates. The loss of enzymic activity at pH 7 is proportional to the combined loss of these residues. The enzymic activity toward RNA is 20-25% of that of native RNAase at pH 7, and 90-100% at pH 5. In the absence of an active site ligand, arginine-10 is also modified with the loss of almost all enzymic activity, although arginine-10 is not an active-site residue. Arginine-33 is unreactive. Kethoxal-modified RNAase undergoes cross-linking in solution at pH 7 or in the freeze-dried state, Incubation at pH 9 in the presence of homoarginine results in partial regeneration of arginyl residues and activity at pH 7. Kethoxal modification of arginines-39 and -85 appears to raise the pK of lysine-41 by about 1 unit, as indicated ty the pH dependence of arylation by 2-carboxy-4,6-dinitrochlorobenzene. The claims of Patthy and Smith (J. Biol, Chem. (1975) 250, 565-569), and of Takahashi (J. Biol. Chem. (1968) 243, 6171-6179) that arginine-39 is a more important functional residue than is arginine-85 are questioned."}
{"id": "PMID:14700", "title": "Low pH stability of alpha-1-antititrypsin.", "content": "According to the previous findings of others, the trypsin inhibitory capacity of alpha-1-antitrypsin is irreversibly lost in acidic solutions below pH 5.0. In contrast, experiments reported herein show that considerable inhibitory activity can be regenerated as a time-dependent phenomena following titration to basic media. The rate of recovery of activity is accompanied by a decreasing amplitude in the fluorescent emission spectrum at 335 nm of acidified alpha-1-antitrypsin solutions following adjustment to pH 8.0. Acidic media also results in the slow, progressive formation of protein aggregates as measured using Sephadex gel filtration. This latter process is more prominent at pH 4.0, near the isoelectric point of alpha-1-antitrypsin than at pH 3 or 2. Both monomer and polymeric forms of alpha-1-antititrypsin were isolated before or after adjustment to basic media. Isolated monomeric material shows a high recovery of biological and immunological activity; aggregate forms, however, are immunologically cross-reactive but show little enzyme inhibitory activity.", "contents": "Low pH stability of alpha-1-antititrypsin. According to the previous findings of others, the trypsin inhibitory capacity of alpha-1-antitrypsin is irreversibly lost in acidic solutions below pH 5.0. In contrast, experiments reported herein show that considerable inhibitory activity can be regenerated as a time-dependent phenomena following titration to basic media. The rate of recovery of activity is accompanied by a decreasing amplitude in the fluorescent emission spectrum at 335 nm of acidified alpha-1-antitrypsin solutions following adjustment to pH 8.0. Acidic media also results in the slow, progressive formation of protein aggregates as measured using Sephadex gel filtration. This latter process is more prominent at pH 4.0, near the isoelectric point of alpha-1-antitrypsin than at pH 3 or 2. Both monomer and polymeric forms of alpha-1-antititrypsin were isolated before or after adjustment to basic media. Isolated monomeric material shows a high recovery of biological and immunological activity; aggregate forms, however, are immunologically cross-reactive but show little enzyme inhibitory activity."}
{"id": "PMID:14702", "title": "The subunit characterization of Callinectes sapidus hemocyanin.", "content": "Hemocyanin from the blue crab, Callinectes sapidus, sediments at 25.7 S and has a native molecular weight of 940 000 +/- 20 000. Under solution conditions of increased pH (approximately 10) or ionic strength, the native molecule dissociates to a 17 S species. Reversal of this dissociation was unsuccessful. At pH 10 and with the removal of Mg2+, the 17 S species reversibly dissociates to form a subunit species which sediments at 6 S. A comparison of the circular dichroic spectra of the 25.7 S and 6 S hemocyanins suggests that little happens to the structural integrity of the polypeptide backbone upon the two dissociations. Molecular weight estimations under reducing and denaturing conditions indicate that the 6 S hemocyanin species represents the constituent polypeptide chain of the protein molecule. Chemical analysis suggests the presence of a small amount, less than 3%, of carbohydrate bound to the polypeptide chain. Electrophoresis of the hemocyanin in the presence of sodium dodecyl sulfate or urea reveals two major electrophoretic species of either slightly different chemical composition or slightly different polypeptide chain length.", "contents": "The subunit characterization of Callinectes sapidus hemocyanin. Hemocyanin from the blue crab, Callinectes sapidus, sediments at 25.7 S and has a native molecular weight of 940 000 +/- 20 000. Under solution conditions of increased pH (approximately 10) or ionic strength, the native molecule dissociates to a 17 S species. Reversal of this dissociation was unsuccessful. At pH 10 and with the removal of Mg2+, the 17 S species reversibly dissociates to form a subunit species which sediments at 6 S. A comparison of the circular dichroic spectra of the 25.7 S and 6 S hemocyanins suggests that little happens to the structural integrity of the polypeptide backbone upon the two dissociations. Molecular weight estimations under reducing and denaturing conditions indicate that the 6 S hemocyanin species represents the constituent polypeptide chain of the protein molecule. Chemical analysis suggests the presence of a small amount, less than 3%, of carbohydrate bound to the polypeptide chain. Electrophoresis of the hemocyanin in the presence of sodium dodecyl sulfate or urea reveals two major electrophoretic species of either slightly different chemical composition or slightly different polypeptide chain length."}
{"id": "PMID:14703", "title": "Heterogeneity in alpha-lactalbumins. I. Human alpha-lactalbumin.", "content": "alpha-Lactalbumin from human milk shows an heterogeneous behaviour when subjected to ion exchange chromatography with DEAE-Sephadex. Two components have been separated, showing identical patterns in the following studies: amino acid compositions, fluorescence and circular dichroism spectra, transition temperature of denaturation, antigenicity, lactose synthase specifying activity and hydrodynamic properties. After rechromatography of either peak, these two components appeared to be in equilibrium. This equilibrium varies with the temperature and the pH of chromatography. Moreover, an increase of n-alcohol concentration in the eluting buffer also induces an increase of the second protein peak eluting at higher ionic strength. These two peaks seem to be the result of some conformational change induced upon the binding of the protein to the solid anionic matrix.", "contents": "Heterogeneity in alpha-lactalbumins. I. Human alpha-lactalbumin. alpha-Lactalbumin from human milk shows an heterogeneous behaviour when subjected to ion exchange chromatography with DEAE-Sephadex. Two components have been separated, showing identical patterns in the following studies: amino acid compositions, fluorescence and circular dichroism spectra, transition temperature of denaturation, antigenicity, lactose synthase specifying activity and hydrodynamic properties. After rechromatography of either peak, these two components appeared to be in equilibrium. This equilibrium varies with the temperature and the pH of chromatography. Moreover, an increase of n-alcohol concentration in the eluting buffer also induces an increase of the second protein peak eluting at higher ionic strength. These two peaks seem to be the result of some conformational change induced upon the binding of the protein to the solid anionic matrix."}
{"id": "PMID:14704", "title": "Relationship between culture density and catabolite repression of an inducible aliphatic amidase in a thermophilic bacillus.", "content": "A direct correlation between the absorbance of a thermophilic bacillus and specific amidase activity was observed, which was found to depend on the cell density of the culture rather than on the time of contact of the culture with the inducer. Dilution of high density cultures caused the specific amidase activity to decrease. Environmental factors such as pH, concentration of inducer or degree of aeration, and level of NH+4 and glutamate had no effect on amidase synthesis. The decrease in amidase activity upon dilution could not be ascribed to destruction by oxygen or by inactivation or decay. Several lines of evidence suggest that catabolite repression is responsible for the phenomenon described. Succinate-grown cultures gave a stronger dilution effect thatn glutamate-grown cells. The mutant strain E-21, relatively resistant to catabolite repression, did not show the characteristic dilution effect nor the direct correlation between absorbance and specific amidase activity.", "contents": "Relationship between culture density and catabolite repression of an inducible aliphatic amidase in a thermophilic bacillus. A direct correlation between the absorbance of a thermophilic bacillus and specific amidase activity was observed, which was found to depend on the cell density of the culture rather than on the time of contact of the culture with the inducer. Dilution of high density cultures caused the specific amidase activity to decrease. Environmental factors such as pH, concentration of inducer or degree of aeration, and level of NH+4 and glutamate had no effect on amidase synthesis. The decrease in amidase activity upon dilution could not be ascribed to destruction by oxygen or by inactivation or decay. Several lines of evidence suggest that catabolite repression is responsible for the phenomenon described. Succinate-grown cultures gave a stronger dilution effect thatn glutamate-grown cells. The mutant strain E-21, relatively resistant to catabolite repression, did not show the characteristic dilution effect nor the direct correlation between absorbance and specific amidase activity."}
{"id": "PMID:14705", "title": "Biosynthesis of dimethyl selenide from sodium selenite in rat liver and kidney cell-free systems.", "content": "A pathway for the synthesis of dimethyl selenide from sodium selenite was studied in rat liver and kidney fractions under anaerobic conditions in the presence of GSH, a NADPH-generating system, and S-adenosylmethionine. Chromatography of liver or kidney soluble fraction on Sephadex G-75 yielded a Fraction C (30,000 molecular weight) which synthesized dimethyl selenide, but at a low rate. Addition of proteins eluting at the void volume (Fraction A) to Fraction C restored full activity. Fractionation of Fraction A on DEAE-cellulose revealed that its ability to stimulate Fraction C was associated with two fractions, one containing glutathione reductase and the other a NADPH-dependent disulfide reductase. It was concluded that Fraction C contains a methyltransferase acting on small amounts of hydrogen selenide produced non-enzymically by the reaction of selenite with GSH, and that stimulation by Fraction A results partly from the NADPH-linked formation of hydrogen selenide catalyzed by glutathione reductase present in Fraction A. Washed liver microsomal fraction incubated with selenite plus 20 mM GSH also synthesized dimethyl selenide, but addition of soluble fraction stimulated activity. A synergistic effect was obtained when liver soluble fraction was added to microsomal fraction in the presence of a physiological level of GSH (2 mM), whereas at 20 mM GSH the effect was merely additive. The microsomal component of the liver system was labile, had maximal activity around pH 7.5, and was exceedingly sensitive to NaAsO2 (93% inhibition by 10(-6) M arsenite in the presence of a 20,000-fold excess of GSH). The microsomal activity apparently results from a Se-methyltransferase, possibly a dithiol protein, that methylates hydrogen selenide produced enzymically by the soluble fraction or non-enzymically when a sufficiently high concentration of GSH is used.", "contents": "Biosynthesis of dimethyl selenide from sodium selenite in rat liver and kidney cell-free systems. A pathway for the synthesis of dimethyl selenide from sodium selenite was studied in rat liver and kidney fractions under anaerobic conditions in the presence of GSH, a NADPH-generating system, and S-adenosylmethionine. Chromatography of liver or kidney soluble fraction on Sephadex G-75 yielded a Fraction C (30,000 molecular weight) which synthesized dimethyl selenide, but at a low rate. Addition of proteins eluting at the void volume (Fraction A) to Fraction C restored full activity. Fractionation of Fraction A on DEAE-cellulose revealed that its ability to stimulate Fraction C was associated with two fractions, one containing glutathione reductase and the other a NADPH-dependent disulfide reductase. It was concluded that Fraction C contains a methyltransferase acting on small amounts of hydrogen selenide produced non-enzymically by the reaction of selenite with GSH, and that stimulation by Fraction A results partly from the NADPH-linked formation of hydrogen selenide catalyzed by glutathione reductase present in Fraction A. Washed liver microsomal fraction incubated with selenite plus 20 mM GSH also synthesized dimethyl selenide, but addition of soluble fraction stimulated activity. A synergistic effect was obtained when liver soluble fraction was added to microsomal fraction in the presence of a physiological level of GSH (2 mM), whereas at 20 mM GSH the effect was merely additive. The microsomal component of the liver system was labile, had maximal activity around pH 7.5, and was exceedingly sensitive to NaAsO2 (93% inhibition by 10(-6) M arsenite in the presence of a 20,000-fold excess of GSH). The microsomal activity apparently results from a Se-methyltransferase, possibly a dithiol protein, that methylates hydrogen selenide produced enzymically by the soluble fraction or non-enzymically when a sufficiently high concentration of GSH is used."}
{"id": "PMID:14706", "title": "Cathepsin D of mouse leukemia L1210 cells. Unusual intracellular localization and biochemical properties.", "content": "Mouse leukemia L1210 cells contain lysosomes, but cathepsin D, a typical lysosomal enzyme, has an unusual localization. After fractionation of homogenates of L1210 cells by isopycnic density gradient centrifugation, most of the activity for all of the acid hydrolases studied, except cathepsin D, is sedimentable and shows a similar density distribution around a peak having a modal density of 1.16. In contrast, much more of the total activity for cathepsin D is not sedimentable, while the sedimentable activity has a distribution around a peak at a higher density of 1.18. After chromatography on Sephadex G-100 of cell extracts, two molecular weight forms of cathepsin D are found. One has an apparent molecular weight of approx. 45,000, similar to rat liver cathepsin D, while the apparent molecular weight of the second form is approx. 95,000. Both forms are 4-5 times more active than rat liver cathepsin D. The high molecular weight L1210 cathepsin D converts to the low molecular weight form with no loss in activity after treatment with beta-mercaptoethanol. In all respects the unusual intracellular localization and molecular weight forms of cathepsin D in mouse leukemia L1210 cells are similar to the situation found for rat thoracic duct lymphocytes.", "contents": "Cathepsin D of mouse leukemia L1210 cells. Unusual intracellular localization and biochemical properties. Mouse leukemia L1210 cells contain lysosomes, but cathepsin D, a typical lysosomal enzyme, has an unusual localization. After fractionation of homogenates of L1210 cells by isopycnic density gradient centrifugation, most of the activity for all of the acid hydrolases studied, except cathepsin D, is sedimentable and shows a similar density distribution around a peak having a modal density of 1.16. In contrast, much more of the total activity for cathepsin D is not sedimentable, while the sedimentable activity has a distribution around a peak at a higher density of 1.18. After chromatography on Sephadex G-100 of cell extracts, two molecular weight forms of cathepsin D are found. One has an apparent molecular weight of approx. 45,000, similar to rat liver cathepsin D, while the apparent molecular weight of the second form is approx. 95,000. Both forms are 4-5 times more active than rat liver cathepsin D. The high molecular weight L1210 cathepsin D converts to the low molecular weight form with no loss in activity after treatment with beta-mercaptoethanol. In all respects the unusual intracellular localization and molecular weight forms of cathepsin D in mouse leukemia L1210 cells are similar to the situation found for rat thoracic duct lymphocytes."}
{"id": "PMID:14707", "title": "Specific inhibition of the synthesis of putrescine and spermidine by 1,3-diaminopropane in rat liver in vivo.", "content": "Chronic administration of 1,3-diaminopropane, a compound inhibiting mammalian ornithine decarboxylase (EC 4.1.1.17) in vivo, effectively prevented the large increases in the concentration of putrescine that normally occur during rat liver regeneration. Furthermore, repeated injections of diaminopropane depressed by more than 85% ornithine decarboxylase activity in rat kidney. Administration of diaminopropane 60 min before partial hepatectomy only marginally inhibited ornithine decarboxylase activity at 4 h after the operation. However, when the compound was given at the time of the operation (4 h before death), or any time thereafter, it virtually abolished the enhancement in ornithine decarboxylase activity in regenerating rat liver remnant. An injection of diaminopropane given 30 to 60 min after operation, but not earlier or later, depressed S-adenosyl-L-methionine decarboxylase activity (EC 4.1.1.50) 4 h after partial hepatectomy. Diaminopropane likewise inhibited ornithine decarboxylase activity during later periods of liver regeneration. In contrast to early regeneration, a total inhibition of the enzyme activity was only achieved when the injection was given not earlier than 2 to 3 h before the death of the animals. Diaminopropane also exerted an acute inhibitory effect on adenosylmethionine decarboxylase activity in 28-h regenerating liver whereas it invariably enhanced the activity of tyrosine aminotransferase (EC 2.6.1.5), used as a standard enzyme of short half-life. Treatment of the rats with diaminopropane entirely abolished the stimulation of spermidien synthesis in vivo from [14C]methionine 4 h after partial hepatectomy or after administration of porcine growth hormone. Both partial hepatectomy and the treatment with growth hormone produced a clear stimulation of hepatic RNA synthesis, the extent of which was not altered by injections of diaminopropane in doses sufficient to prevent any enhancement of ornithine decarboxylase activity and spermidine synthesis.", "contents": "Specific inhibition of the synthesis of putrescine and spermidine by 1,3-diaminopropane in rat liver in vivo. Chronic administration of 1,3-diaminopropane, a compound inhibiting mammalian ornithine decarboxylase (EC 4.1.1.17) in vivo, effectively prevented the large increases in the concentration of putrescine that normally occur during rat liver regeneration. Furthermore, repeated injections of diaminopropane depressed by more than 85% ornithine decarboxylase activity in rat kidney. Administration of diaminopropane 60 min before partial hepatectomy only marginally inhibited ornithine decarboxylase activity at 4 h after the operation. However, when the compound was given at the time of the operation (4 h before death), or any time thereafter, it virtually abolished the enhancement in ornithine decarboxylase activity in regenerating rat liver remnant. An injection of diaminopropane given 30 to 60 min after operation, but not earlier or later, depressed S-adenosyl-L-methionine decarboxylase activity (EC 4.1.1.50) 4 h after partial hepatectomy. Diaminopropane likewise inhibited ornithine decarboxylase activity during later periods of liver regeneration. In contrast to early regeneration, a total inhibition of the enzyme activity was only achieved when the injection was given not earlier than 2 to 3 h before the death of the animals. Diaminopropane also exerted an acute inhibitory effect on adenosylmethionine decarboxylase activity in 28-h regenerating liver whereas it invariably enhanced the activity of tyrosine aminotransferase (EC 2.6.1.5), used as a standard enzyme of short half-life. Treatment of the rats with diaminopropane entirely abolished the stimulation of spermidien synthesis in vivo from [14C]methionine 4 h after partial hepatectomy or after administration of porcine growth hormone. Both partial hepatectomy and the treatment with growth hormone produced a clear stimulation of hepatic RNA synthesis, the extent of which was not altered by injections of diaminopropane in doses sufficient to prevent any enhancement of ornithine decarboxylase activity and spermidine synthesis."}
{"id": "PMID:14708", "title": "Electron spin relaxation time of Fe(III) in high spin heme proteins.", "content": "The electron spin relaxation time of high spin Fe(III), taus, was determined from the frequency dependence (5-100 MHz) of the longitudinal proton relaxation rates of water in solutions of catalase, metmyoglobin and acid ferricytochrome c. In all three high-spin heme proteins the relaxation rates incrased below 25 MHz, while no frequency dependence was observed above that frequency. The results are interpreted by assuming that taus, which modulates the dipolar interaction between the unpaired electrons of the iron and the water protons, is frequently independent. Its value was determined to be (6 +/- 1) - 10(-11) s.", "contents": "Electron spin relaxation time of Fe(III) in high spin heme proteins. The electron spin relaxation time of high spin Fe(III), taus, was determined from the frequency dependence (5-100 MHz) of the longitudinal proton relaxation rates of water in solutions of catalase, metmyoglobin and acid ferricytochrome c. In all three high-spin heme proteins the relaxation rates incrased below 25 MHz, while no frequency dependence was observed above that frequency. The results are interpreted by assuming that taus, which modulates the dipolar interaction between the unpaired electrons of the iron and the water protons, is frequently independent. Its value was determined to be (6 +/- 1) - 10(-11) s."}
{"id": "PMID:14709", "title": "The 5,5-dimethyloxazolidine-2[14C],4-dione distribution technique and the measurement of intracellular pH in Acer pseudoplatanus cells.", "content": "The intracellular pH of suspension-cultured Acer pseudoplatanus cells, was estimated from the distribution of 5,5-dimethyloxazolidine-2[14C],4-dione (DMO) between the culture medium and the cells. The metabolization of DMO in this biological system introduces an error in the calculated intracellular pH value. Three methods are given to overcome this difficulty and to estimate the equilibrium between intracellular and extracellular DMO molecules. A preliminary study has shown that the intracellular pH remains constant about 6.5 when the extracellular pH increases from 5.6 to 7.3.", "contents": "The 5,5-dimethyloxazolidine-2[14C],4-dione distribution technique and the measurement of intracellular pH in Acer pseudoplatanus cells. The intracellular pH of suspension-cultured Acer pseudoplatanus cells, was estimated from the distribution of 5,5-dimethyloxazolidine-2[14C],4-dione (DMO) between the culture medium and the cells. The metabolization of DMO in this biological system introduces an error in the calculated intracellular pH value. Three methods are given to overcome this difficulty and to estimate the equilibrium between intracellular and extracellular DMO molecules. A preliminary study has shown that the intracellular pH remains constant about 6.5 when the extracellular pH increases from 5.6 to 7.3."}
{"id": "PMID:14710", "title": "The effect of 5-hydroxytryptamine and other indole derivatives on the formation of adenosine 3',5'-cyclic monophosphate in pigeon erythrocytes.", "content": "1. The effect of insulin, acetylcholine, histamine, 5-hydroxytryptamine and prostaglandins E1, E2 and F2alpha on basal and adrenalin-stimulated cyclic AMP content in intact pigeon erythrocytes was investigated. 2. None of these compounds influenced basal cyclic AMP contest, and only 5-hydroxytryptamine antagonized the effect of adrenalin. The increase in cyclic AMP with 0.55 micronM adrenalin was inhibited by approx. 60% in the presence of 10 muM 5-hydroxytryptamine. The interaction between adrenalin and 5-hydroxytryptamine was competitive. 3. 5-Hydroxytryptamine did not affect the rate of degradation of cyclic AMP in intact cells, but did inhibit adrenalin-stimulated cyclic AMP formation in permeable or resealed cell \"ghosts\". 4. The effect of 5-hydroxytryptamine to inhibit cyclic AMP accumulation was not dependent on the presence of Ca2+, in either intact cells or \"ghosts\". 5. Various indole derivatives and other compounds were tested for their ability to inhibit the effect of adrenalin on cyclic AMP accumulation. Only those derivatives with a free amino group and net positive charge in the side chain were effective. 6. It was concluded that 5-hydroxytryptamine inhibits adrenalin-stimulated adenylate cyclase activity in pigeon erythrocytes, possibly by competing with adrenalin for binding to the beta-adrenergic receptor.", "contents": "The effect of 5-hydroxytryptamine and other indole derivatives on the formation of adenosine 3',5'-cyclic monophosphate in pigeon erythrocytes. 1. The effect of insulin, acetylcholine, histamine, 5-hydroxytryptamine and prostaglandins E1, E2 and F2alpha on basal and adrenalin-stimulated cyclic AMP content in intact pigeon erythrocytes was investigated. 2. None of these compounds influenced basal cyclic AMP contest, and only 5-hydroxytryptamine antagonized the effect of adrenalin. The increase in cyclic AMP with 0.55 micronM adrenalin was inhibited by approx. 60% in the presence of 10 muM 5-hydroxytryptamine. The interaction between adrenalin and 5-hydroxytryptamine was competitive. 3. 5-Hydroxytryptamine did not affect the rate of degradation of cyclic AMP in intact cells, but did inhibit adrenalin-stimulated cyclic AMP formation in permeable or resealed cell \"ghosts\". 4. The effect of 5-hydroxytryptamine to inhibit cyclic AMP accumulation was not dependent on the presence of Ca2+, in either intact cells or \"ghosts\". 5. Various indole derivatives and other compounds were tested for their ability to inhibit the effect of adrenalin on cyclic AMP accumulation. Only those derivatives with a free amino group and net positive charge in the side chain were effective. 6. It was concluded that 5-hydroxytryptamine inhibits adrenalin-stimulated adenylate cyclase activity in pigeon erythrocytes, possibly by competing with adrenalin for binding to the beta-adrenergic receptor."}
{"id": "PMID:14711", "title": "Characteristics of the cyclic nucleotide phosphodiesterases of normal and leukemic lymphocytes.", "content": "The specific activity of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase of leukemic lymphocytes was 5-10-fold greater than that of purified normal lymphocytes or of homogenates of spleen, thymus or lymph nodes of normal mice. This rise was demonstrable over a wide range of substrate concentrations. Both normal and leukemic lymphocytes contained a heat-stable, calcium-dependent activator of phosphodiesterase. However, the increased activity of phosphodiesterase in leukemic lymphocytes was not due to this protein activator since (a) phosphodiesterase activity from these cells was not stimulated by this activator and (b) phosphodiesterase activity of leukemic lymphocytes was not inhibited by the calcium chelater, ethylene-glycol-bis,(beta-aminoethylether)-N,N'-tetraacetic acid, suggesting that the enzyme was not already maximally activated. A comparison of several other properties of phosphodiesterase from normal and leukemic lymphocytes showed that the enzymes have similar pH optima, similar stabilities to freezing and thawing and similar sensitivities to inhibition by the phosphodiesterase inhibitors, chlorpromazine, papaverine and isobutylmethylxanthine. However, the subcellular distribution of the phosphodiesterases was different, and the phosphodiesterase of leukemic lymphocytes was significantly more resistant to heat than that of normal lymphocytes. Although no differences were found between the phosphodiesterases of normal and leukemic lymphocytes in their sensitivities to drugs, there were marked differences in drug sensitivity between the phosphodiesterase of lymphocytes and that of other tissue. For example, concentrations of chlorpromazine which inhibited phosphodiesterase of cerebrum by 70% had no effect on phosphodiesterase activity of lymphocytes. On the othere hand, the papaverine-induced inhibition of phosphodiesterase was similar in lymphocytes and cerebrum. Since an optimal concentration of cyclic nucleotides is essential to maintain normal cell growth, these results suggest that the abnormal growth characteristics of leukemic lymphocytes may be explained by their high activity of phosphodiesterase. Furthermore, the qualitative and quantitiative differences between the phosphodiesterases of leukemic lymphocytes and other tissues raise the possibility of selectively inhibiting the phosphodiesterase of the leukemic lymphocytes, thereby reducing their rate of growth, without affecting other tissues.", "contents": "Characteristics of the cyclic nucleotide phosphodiesterases of normal and leukemic lymphocytes. The specific activity of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase of leukemic lymphocytes was 5-10-fold greater than that of purified normal lymphocytes or of homogenates of spleen, thymus or lymph nodes of normal mice. This rise was demonstrable over a wide range of substrate concentrations. Both normal and leukemic lymphocytes contained a heat-stable, calcium-dependent activator of phosphodiesterase. However, the increased activity of phosphodiesterase in leukemic lymphocytes was not due to this protein activator since (a) phosphodiesterase activity from these cells was not stimulated by this activator and (b) phosphodiesterase activity of leukemic lymphocytes was not inhibited by the calcium chelater, ethylene-glycol-bis,(beta-aminoethylether)-N,N'-tetraacetic acid, suggesting that the enzyme was not already maximally activated. A comparison of several other properties of phosphodiesterase from normal and leukemic lymphocytes showed that the enzymes have similar pH optima, similar stabilities to freezing and thawing and similar sensitivities to inhibition by the phosphodiesterase inhibitors, chlorpromazine, papaverine and isobutylmethylxanthine. However, the subcellular distribution of the phosphodiesterases was different, and the phosphodiesterase of leukemic lymphocytes was significantly more resistant to heat than that of normal lymphocytes. Although no differences were found between the phosphodiesterases of normal and leukemic lymphocytes in their sensitivities to drugs, there were marked differences in drug sensitivity between the phosphodiesterase of lymphocytes and that of other tissue. For example, concentrations of chlorpromazine which inhibited phosphodiesterase of cerebrum by 70% had no effect on phosphodiesterase activity of lymphocytes. On the othere hand, the papaverine-induced inhibition of phosphodiesterase was similar in lymphocytes and cerebrum. Since an optimal concentration of cyclic nucleotides is essential to maintain normal cell growth, these results suggest that the abnormal growth characteristics of leukemic lymphocytes may be explained by their high activity of phosphodiesterase. Furthermore, the qualitative and quantitiative differences between the phosphodiesterases of leukemic lymphocytes and other tissues raise the possibility of selectively inhibiting the phosphodiesterase of the leukemic lymphocytes, thereby reducing their rate of growth, without affecting other tissues."}
{"id": "PMID:14712", "title": "[Electron transfer through the octane/water interface in the presence of chlorophyll].", "content": "The data obtained by the vibrating electrode method in the investigation of the system octane/water containing chlorophyll adsorbed on the interface and redox systems in both phases show that chlorophyll is capable in the absence of illumination to transfer electrons from one redox reaction to another one, injecting charges from water into octane. It was shown that charge transfer reaction accompanied by proton injection in the unstirred interfacial layer.", "contents": "[Electron transfer through the octane/water interface in the presence of chlorophyll]. The data obtained by the vibrating electrode method in the investigation of the system octane/water containing chlorophyll adsorbed on the interface and redox systems in both phases show that chlorophyll is capable in the absence of illumination to transfer electrons from one redox reaction to another one, injecting charges from water into octane. It was shown that charge transfer reaction accompanied by proton injection in the unstirred interfacial layer."}
{"id": "PMID:14717", "title": "[Adenylate kinase of plants. Properties of adenylate kinase of pea leaves].", "content": "The properties of adenylate kinase in 2 ADP in equilibrium ATP + AMP reaction have been studied. The dependence of the enzyme activity on medium pH, protein concentration, substrates, Mg++ ions, AMP, adenine and adenosine has been also investigated. pH optimum is found to be 8.5 for forward reaction and 8-9--for the reverse one. The Michaelis constants are as follows: for ADP--1.17-10(-4) M, for ATP--3.33-10(-4) M at 24 degrees C, in 50 mM tris-HCl pH 7.6. The optimal ratio, Mg++ ions/substrates (ADP, ATP + AMP), is 1:2. The chelates of adenine nucleotides with Mg++ ions are proved to be \"true\" reaction substrates. Unlike adenine and adenosine, the product of AMP reaction inhibits adenylate kinase activity. It is concluded that the properties of adenylate kinase in plants are similar to those of animals and humans (moikinase).", "contents": "[Adenylate kinase of plants. Properties of adenylate kinase of pea leaves]. The properties of adenylate kinase in 2 ADP in equilibrium ATP + AMP reaction have been studied. The dependence of the enzyme activity on medium pH, protein concentration, substrates, Mg++ ions, AMP, adenine and adenosine has been also investigated. pH optimum is found to be 8.5 for forward reaction and 8-9--for the reverse one. The Michaelis constants are as follows: for ADP--1.17-10(-4) M, for ATP--3.33-10(-4) M at 24 degrees C, in 50 mM tris-HCl pH 7.6. The optimal ratio, Mg++ ions/substrates (ADP, ATP + AMP), is 1:2. The chelates of adenine nucleotides with Mg++ ions are proved to be \"true\" reaction substrates. Unlike adenine and adenosine, the product of AMP reaction inhibits adenylate kinase activity. It is concluded that the properties of adenylate kinase in plants are similar to those of animals and humans (moikinase)."}
{"id": "PMID:14713", "title": "[Several physical aspects of intracellular energy transformation].", "content": "Physical principles underlying the chemiosmotic hypothesis of membrane phosphorylation are analysed. The utilization of free energy determined by dydrogen ions concentration difference across the membrane for ATP synthesis requires ATP-synthetase to be an entropy machine able to perform work on account of heat. The chemiosmotic hypothesis assumes the possibility of interchangeable utilization of both components of proton electrochemical potential-the membrane electrical difference and proton concentration gradient-for ATP synthesis. This assumption requires the fulfillment of practically unrealizable conditions. Energetic coupling of intracellular chemical reactions must be realized by means of a mechanism in which every act of energydonating reaction leads compulsory to one act of energyaccepting reaction. For such a mechanism both reactions ought to proceed essentially in one elementary act. For intracellular macromolecular and supramolecular systems it implies the necessity of excitation of specific mechanical slowly relaxing degrees of freedom.", "contents": "[Several physical aspects of intracellular energy transformation]. Physical principles underlying the chemiosmotic hypothesis of membrane phosphorylation are analysed. The utilization of free energy determined by dydrogen ions concentration difference across the membrane for ATP synthesis requires ATP-synthetase to be an entropy machine able to perform work on account of heat. The chemiosmotic hypothesis assumes the possibility of interchangeable utilization of both components of proton electrochemical potential-the membrane electrical difference and proton concentration gradient-for ATP synthesis. This assumption requires the fulfillment of practically unrealizable conditions. Energetic coupling of intracellular chemical reactions must be realized by means of a mechanism in which every act of energydonating reaction leads compulsory to one act of energyaccepting reaction. For such a mechanism both reactions ought to proceed essentially in one elementary act. For intracellular macromolecular and supramolecular systems it implies the necessity of excitation of specific mechanical slowly relaxing degrees of freedom."}
{"id": "PMID:14718", "title": "[Effect of pH on the kinetics of the reaction catalyzed by beta-D-hexosaminidase from Halocynthia roretzi].", "content": "The analysis of the pH-dependence of Michaelis constant and maximal velocity for the reaction catalyzed by beta-D-hexosaminidase from Halocynthia roretzi revealed two essential ionazable groups of the enzyme. One of them controls substrate binding and has a pKa of 5.5 in free enzyme. The other group (pKa=5.6) is necessary for the occurrence of the catalytic step and appears not to change its pKa on substrate binding.", "contents": "[Effect of pH on the kinetics of the reaction catalyzed by beta-D-hexosaminidase from Halocynthia roretzi]. The analysis of the pH-dependence of Michaelis constant and maximal velocity for the reaction catalyzed by beta-D-hexosaminidase from Halocynthia roretzi revealed two essential ionazable groups of the enzyme. One of them controls substrate binding and has a pKa of 5.5 in free enzyme. The other group (pKa=5.6) is necessary for the occurrence of the catalytic step and appears not to change its pKa on substrate binding."}
{"id": "PMID:14714", "title": "[Structural lability of biomembranes and their components studied by fluorescent analysis. V. Liposomes].", "content": "The nature of binding of ionic and neutral fluorescent probes in liposome structures of natural lecithin at various pH and ionic strength of the medium. Temperature relationship of fluorescence intensity of both probes presented in Arrhenius coordinates is shown to have bends at 32--42degrees C. A smaller bend in the temperature range of 20--40degrees C is fixed while studying the correlation time of the spin probe, line width of (CH2)n groups in the NMR-spectrum and light scattering at the angle of 90 degrees. Differences between the sensitivity of these procedures to the phase transition in the lipid structure and the method of measuring fluorescence probe intensity is discussed in terms of literature data.", "contents": "[Structural lability of biomembranes and their components studied by fluorescent analysis. V. Liposomes]. The nature of binding of ionic and neutral fluorescent probes in liposome structures of natural lecithin at various pH and ionic strength of the medium. Temperature relationship of fluorescence intensity of both probes presented in Arrhenius coordinates is shown to have bends at 32--42degrees C. A smaller bend in the temperature range of 20--40degrees C is fixed while studying the correlation time of the spin probe, line width of (CH2)n groups in the NMR-spectrum and light scattering at the angle of 90 degrees. Differences between the sensitivity of these procedures to the phase transition in the lipid structure and the method of measuring fluorescence probe intensity is discussed in terms of literature data."}
{"id": "PMID:14719", "title": "[Conditions of spontaneous gelatinization of sarcoplasmic proteins].", "content": "Ca2+ ions at low concentration (10(-4)-10(-5) M) when added to ultracentrifugates of sarcoplasmic proteins with minimal content of sarcoplasmic reticulum fragments completely prevent protein gelatinization or gels, formed in these conditions, quickly dilute. Ca2+ ions at the concentration of 10(-3) M prevented in these conditions gelatinization in all the cases studied. Strong gels of sarcoplasmic proteins are formed afterwards in weak acid (pH 6.1-6.75), neutral (pH 7.0) and weak alkaline (pH 7.25-7.45 and higher) media. It is suggested that gelatinization of sarcoplasmic proteins is closely related with the development of plastic tonus, obturatory muscle function and viscous after-effect.", "contents": "[Conditions of spontaneous gelatinization of sarcoplasmic proteins]. Ca2+ ions at low concentration (10(-4)-10(-5) M) when added to ultracentrifugates of sarcoplasmic proteins with minimal content of sarcoplasmic reticulum fragments completely prevent protein gelatinization or gels, formed in these conditions, quickly dilute. Ca2+ ions at the concentration of 10(-3) M prevented in these conditions gelatinization in all the cases studied. Strong gels of sarcoplasmic proteins are formed afterwards in weak acid (pH 6.1-6.75), neutral (pH 7.0) and weak alkaline (pH 7.25-7.45 and higher) media. It is suggested that gelatinization of sarcoplasmic proteins is closely related with the development of plastic tonus, obturatory muscle function and viscous after-effect."}
{"id": "PMID:14716", "title": "[Effect of Ca ions and pH on the osmotic potential across the epithelium of the small intestine].", "content": "It was found that kinetic features of the behaviour of osmotic potential differences through epithelial cells layer were characteristic of determination of mechanic properties of separate structures of intercellular junctions. The quantitative estimation of the contribution of tight junction and simple junctions to the value of mechanic connection was performed. The mechanism of structure reorganisation in intercellular junctions under osmotic pressure are discussed. A model of intercellular junctions that accounts for the essential feature of transepithelial potential differences behavior under the osmotic pressure is proposed.", "contents": "[Effect of Ca ions and pH on the osmotic potential across the epithelium of the small intestine]. It was found that kinetic features of the behaviour of osmotic potential differences through epithelial cells layer were characteristic of determination of mechanic properties of separate structures of intercellular junctions. The quantitative estimation of the contribution of tight junction and simple junctions to the value of mechanic connection was performed. The mechanism of structure reorganisation in intercellular junctions under osmotic pressure are discussed. A model of intercellular junctions that accounts for the essential feature of transepithelial potential differences behavior under the osmotic pressure is proposed."}
{"id": "PMID:14720", "title": "[Isolation and properties of tripolyphosphatase from Neurospora crassa].", "content": "Homogenous preparation of tripolyphosphatase from Neurospora crassa is obtained. The enzyme is found to consist of two equal subunits with molecular weight of 40 000 and to have pH optimum 7.0 and temperature optimum 50 degrees C. Bivalent metal ions are required for its catalytical activity, the hest activators being Co2+, Mg2+ and Mn2+. Strict specificity of the enzyme to tripolyphosphate is demonstrated, Km being 5.9-10(-4) M. The enzyme hydrolyses tripolyphosphate to equimolar mixture of ortho- and pyrophosphate. The enzyme activity depends on orthophosphate and pyrophosphate concentrations in the incubation medium.", "contents": "[Isolation and properties of tripolyphosphatase from Neurospora crassa]. Homogenous preparation of tripolyphosphatase from Neurospora crassa is obtained. The enzyme is found to consist of two equal subunits with molecular weight of 40 000 and to have pH optimum 7.0 and temperature optimum 50 degrees C. Bivalent metal ions are required for its catalytical activity, the hest activators being Co2+, Mg2+ and Mn2+. Strict specificity of the enzyme to tripolyphosphate is demonstrated, Km being 5.9-10(-4) M. The enzyme hydrolyses tripolyphosphate to equimolar mixture of ortho- and pyrophosphate. The enzyme activity depends on orthophosphate and pyrophosphate concentrations in the incubation medium."}
{"id": "PMID:14721", "title": "[Isolation and some properties of Ca2+-, Mg2+-dependent deoxyribonuclease from sea urchin (Strongylocentrotus intermedius) embryos].", "content": "Ca2+-Mg2+-dependent deoxyribonuclease (deoxyribonucleate-5'-oligonucleotidehydrolase E. C. 3.1.4.5). Molecular weight of the enzyme is found to be 40 000 daltons isoelectric point--4.4. The enzyme degraded DNA only in the presence of bivalent cations. It hydrolyses preferentially native DNA with pH optimum 7.0-7.2 in the presence of Mg2+ ions. Ca2+ ions shift the pH optimum to 8.0-8.5. Combined addition of Ca2+ and Mg2+ ions results in a sinergic effect and changes the enzyme specificity to the secondary DNA structure. The enzyme hydrolyses both native and denatured DNA by the endonucleolytic type to form oligonucleotides with 5' terminal phosphate the content of tetra-octanucleotides being 80-85%.", "contents": "[Isolation and some properties of Ca2+-, Mg2+-dependent deoxyribonuclease from sea urchin (Strongylocentrotus intermedius) embryos]. Ca2+-Mg2+-dependent deoxyribonuclease (deoxyribonucleate-5'-oligonucleotidehydrolase E. C. 3.1.4.5). Molecular weight of the enzyme is found to be 40 000 daltons isoelectric point--4.4. The enzyme degraded DNA only in the presence of bivalent cations. It hydrolyses preferentially native DNA with pH optimum 7.0-7.2 in the presence of Mg2+ ions. Ca2+ ions shift the pH optimum to 8.0-8.5. Combined addition of Ca2+ and Mg2+ ions results in a sinergic effect and changes the enzyme specificity to the secondary DNA structure. The enzyme hydrolyses both native and denatured DNA by the endonucleolytic type to form oligonucleotides with 5' terminal phosphate the content of tetra-octanucleotides being 80-85%."}
{"id": "PMID:14722", "title": "[Protease from bovine spleen with kininogenase activity].", "content": "A protease with kininogenase activity at pH 7.5 was isolated from bovine spleen extract by gel filtration and ion exchange chromatography. The protease was found in the fraction with molecular weight lower than 25.000 and was separated from the other neutral SH-dependent protease by chromatography on KM-cellulose. The kininogenase activity was inhibited by DFP and trasylol; soybean trypsin inhibitor had no effect. The protease did not split N-benzoyl-L-arginine ethyl ester and N-benzoyl-D, L-arginine p-nitroanilide.", "contents": "[Protease from bovine spleen with kininogenase activity]. A protease with kininogenase activity at pH 7.5 was isolated from bovine spleen extract by gel filtration and ion exchange chromatography. The protease was found in the fraction with molecular weight lower than 25.000 and was separated from the other neutral SH-dependent protease by chromatography on KM-cellulose. The kininogenase activity was inhibited by DFP and trasylol; soybean trypsin inhibitor had no effect. The protease did not split N-benzoyl-L-arginine ethyl ester and N-benzoyl-D, L-arginine p-nitroanilide."}
{"id": "PMID:14723", "title": "[The activity of beta-hydroxy-beta-methylglutaryl-CoA reductase in the soluble fraction of rat liver].", "content": "Assay conditions are worked out for determination of activity of beta-hydroxy-beta-methylglutaryl-CoA reductase (HMG-CoA reductase) in 140.000 g supernatant fraction of the rat liver. Some kinetic properties of the enzyme are studied: the activity dependency on the incubation time, protein concentration, pH, glutathione, dithiothreitol and HMG-CoA contents in the incubation medium. The effect of Triton WR 1339 on the activity of HMG-CoA reductase in the liver 140.000 g supernatant and microsomal fractions is comparatively studied. Diurnal activity variations of soluble and microsomal enzymes are also investigated. It is suggested that the rat liver HMG-CoA reductase in the 140.000 g supernatant fraction is not identical to the enzyme located in the microsomal fraction.", "contents": "[The activity of beta-hydroxy-beta-methylglutaryl-CoA reductase in the soluble fraction of rat liver]. Assay conditions are worked out for determination of activity of beta-hydroxy-beta-methylglutaryl-CoA reductase (HMG-CoA reductase) in 140.000 g supernatant fraction of the rat liver. Some kinetic properties of the enzyme are studied: the activity dependency on the incubation time, protein concentration, pH, glutathione, dithiothreitol and HMG-CoA contents in the incubation medium. The effect of Triton WR 1339 on the activity of HMG-CoA reductase in the liver 140.000 g supernatant and microsomal fractions is comparatively studied. Diurnal activity variations of soluble and microsomal enzymes are also investigated. It is suggested that the rat liver HMG-CoA reductase in the 140.000 g supernatant fraction is not identical to the enzyme located in the microsomal fraction."}
{"id": "PMID:14724", "title": "[cAMP phosphodiesterase from phototrophic bacteria Rhodospirillum rubrum].", "content": "cAMP phosphodiesterase activity is discovered in supernatant of R. rubrum cell homogenate after centrifugation at 1000 g. The enzyme is highly active (5.62 nmoles/mg of protein per 1 min) at a broad pH range--from 7.0 to 9.0. The enzyme activity is strongly inhibited with caffeine and dithiotreitol and very significantly inhibited by ascorbic acid. The dependence of the enzyme activity on the incubation time and protein and substrate concentrations in the reaction mixture is estimated. cAMP phosphodiesterase is found in soluble fraction and in particule fractions sedimenting at 30 000 g. The enzyme activity is completely absent in washed chromatophores sedimenting at 160 000 g.", "contents": "[cAMP phosphodiesterase from phototrophic bacteria Rhodospirillum rubrum]. cAMP phosphodiesterase activity is discovered in supernatant of R. rubrum cell homogenate after centrifugation at 1000 g. The enzyme is highly active (5.62 nmoles/mg of protein per 1 min) at a broad pH range--from 7.0 to 9.0. The enzyme activity is strongly inhibited with caffeine and dithiotreitol and very significantly inhibited by ascorbic acid. The dependence of the enzyme activity on the incubation time and protein and substrate concentrations in the reaction mixture is estimated. cAMP phosphodiesterase is found in soluble fraction and in particule fractions sedimenting at 30 000 g. The enzyme activity is completely absent in washed chromatophores sedimenting at 160 000 g."}
{"id": "PMID:14725", "title": "[Influence of dinitrophenol, octanol and toluene upon pH-dependence of ca-ATPase activity of heavy meromyosin].", "content": "It is found that dinitrophenol, octanol and toluene produce similar effects on pH-dependence of ATPase of myosin and heavy meromyosin (HMM), i.e. they decrease or remove the neutral suppression of ATPase activity. The appearance of pH-dependence curves is simplified and approaches the form, which is characteristic for the ionisation curve of one; in the last resort two groups, participating in the enzyme activity. The activity of HMM is higher and the zone of the neutral suppression is diminished at low ionic strength, the activation by the modifiers being observed at the significantly lesser degree. CaATPase activation by dinitrophenol, octanol and toluene is suggested to be of the same nature and is accounted for the masking of \"the inhibiting\" ionizable group of the enzyme with near to neutral pK. This masking may be the result of the conformational changes occuring at the deformation of hydrofobic regions. The ionization of \"the activity inhibiting\" group of the enzyme depends directly or indirectly on the concentration of potassium chloride and the increase of KCl concentration bring to the inhibition of ATPase activity.", "contents": "[Influence of dinitrophenol, octanol and toluene upon pH-dependence of ca-ATPase activity of heavy meromyosin]. It is found that dinitrophenol, octanol and toluene produce similar effects on pH-dependence of ATPase of myosin and heavy meromyosin (HMM), i.e. they decrease or remove the neutral suppression of ATPase activity. The appearance of pH-dependence curves is simplified and approaches the form, which is characteristic for the ionisation curve of one; in the last resort two groups, participating in the enzyme activity. The activity of HMM is higher and the zone of the neutral suppression is diminished at low ionic strength, the activation by the modifiers being observed at the significantly lesser degree. CaATPase activation by dinitrophenol, octanol and toluene is suggested to be of the same nature and is accounted for the masking of \"the inhibiting\" ionizable group of the enzyme with near to neutral pK. This masking may be the result of the conformational changes occuring at the deformation of hydrofobic regions. The ionization of \"the activity inhibiting\" group of the enzyme depends directly or indirectly on the concentration of potassium chloride and the increase of KCl concentration bring to the inhibition of ATPase activity."}
{"id": "PMID:14726", "title": "[Mechanism of amylase action on glucoside starch bonds].", "content": "Functional groups of glucoamylase and alpha-amylase from Asp. awamori, alpha-amylase from Asp. oryzae and alpha- and beta-amylases from barley malt are identified. Kinetic curves of the activity dependency on pH, values of ionization heats and photooxidative inactivation draw to the conclusion that carboxyl-imidazole system enters into the active site of the enzymes. A hypothetic mechanism of hydrolysis of alpha-1,4-glucoside bond in starch molecule by alpha- and beta-amylases and of alpha-1,4- and alpha-1,6-glucoside bonds by glucoamylase is given. A theory of induced correspondence of enzyme and substrate satisfactorily explains the specificity of the enzyme action and the cause of complete starch convertion into glucose under glucoamylase action and of terminal starch hydrolysis by alpha- and beta-amylases.", "contents": "[Mechanism of amylase action on glucoside starch bonds]. Functional groups of glucoamylase and alpha-amylase from Asp. awamori, alpha-amylase from Asp. oryzae and alpha- and beta-amylases from barley malt are identified. Kinetic curves of the activity dependency on pH, values of ionization heats and photooxidative inactivation draw to the conclusion that carboxyl-imidazole system enters into the active site of the enzymes. A hypothetic mechanism of hydrolysis of alpha-1,4-glucoside bond in starch molecule by alpha- and beta-amylases and of alpha-1,4- and alpha-1,6-glucoside bonds by glucoamylase is given. A theory of induced correspondence of enzyme and substrate satisfactorily explains the specificity of the enzyme action and the cause of complete starch convertion into glucose under glucoamylase action and of terminal starch hydrolysis by alpha- and beta-amylases."}
{"id": "PMID:14727", "title": "[Serine proteases from Bac. subtilis].", "content": "Using biospecific adsorbent and subsequent gel-filtration of Sephadex G-75 three fractions of serine proteases (I--III) having different physicochemical properties were isolated from Bac. subtilis. The first protease had molecular weight of 23000--24000 (pH optimum 6,5, activation energy 16,6 ccal/mol. The second one had molecular weight of 29000, pH optimum 11,0, activation energy 14,4 ccal/mol. The third protease was a mixture of proteases with average molecular weights 26000 and pH optima at 7,0, 8,5 and 11,0.", "contents": "[Serine proteases from Bac. subtilis]. Using biospecific adsorbent and subsequent gel-filtration of Sephadex G-75 three fractions of serine proteases (I--III) having different physicochemical properties were isolated from Bac. subtilis. The first protease had molecular weight of 23000--24000 (pH optimum 6,5, activation energy 16,6 ccal/mol. The second one had molecular weight of 29000, pH optimum 11,0, activation energy 14,4 ccal/mol. The third protease was a mixture of proteases with average molecular weights 26000 and pH optima at 7,0, 8,5 and 11,0."}
{"id": "PMID:14728", "title": "[Methylation of liver cell chromatin proteins at different stages of post-natal development of albino rats].", "content": "Methylation of acid proteins and various histone fractions of liver cell chromatin was studied. The intensity of methylation of acid proteins of animals, differing in age, was shown to be 8--16 times higher than that for histone methylation, despite the fact that the rates of 2-14C-methionine incorporation into these two groups of proteins were practically the same. The intensity of methylation of acid proteins and total histones significantly increased during the post-natal development of the animals. Histone methylation largely occurred at the expense of the arginine-rich H3 fraction and the H2 fraction with a moderate level of arginine and lysine. Lysine-rich histone fractions were not subjected to methylation. It is assumed that chromatin proteins methylation regulates conformational properties of the complex and matrix properties of the genome.", "contents": "[Methylation of liver cell chromatin proteins at different stages of post-natal development of albino rats]. Methylation of acid proteins and various histone fractions of liver cell chromatin was studied. The intensity of methylation of acid proteins of animals, differing in age, was shown to be 8--16 times higher than that for histone methylation, despite the fact that the rates of 2-14C-methionine incorporation into these two groups of proteins were practically the same. The intensity of methylation of acid proteins and total histones significantly increased during the post-natal development of the animals. Histone methylation largely occurred at the expense of the arginine-rich H3 fraction and the H2 fraction with a moderate level of arginine and lysine. Lysine-rich histone fractions were not subjected to methylation. It is assumed that chromatin proteins methylation regulates conformational properties of the complex and matrix properties of the genome."}
{"id": "PMID:14729", "title": "[Cytosolic alcohol dehydrogenases from yeast Torulopsis candida].", "content": "A comparative study of cell cytosol alcohol dehydrogenase (ADH) from yeast Torulopsis candida IBFM-Y-127 grown on glucose and hexadecane which were the only source of carbon, was made. In both cases ADH had a pH optimum within the range of 7.0--10.0, when various normal primary alcohols (C2--C16) were used. The enzyme was active only in the presence of NAD, which cannot be substituted by NADP. The total activity of ADH decreased approximately 8-fold when the length of hydrocarbon radicals was changed from C2 up to C16. When the cells were grown on hexadecane, only ethyl, n-buthyl, n-amyl and n-hexyl alcohols were active as substrates. The dehydration rate of each alcohol was far lower than that for the cytosol of glucose-grown cells. In the latter case the enzyme activity also decreased with an increase in the alcohol radical from C2 to C6. In all cases studied methyl alcohol and cyclic (cinnamyl alcohol--C8) alcohol were not dehydrated at all. Disc-electrophoresis in polyacrylamide gel, involving gel colouration for the assay of enzyme activity showed that glucose--grown cell cytosol contained three forms of ADH. One of those forms was highly active when short--chain normal primary alcohols were used; this form may be probably regarded as \"classical\" ADH (EC 1.1.1.1). The two other forms caused intensive dehydration of long-chain alcohols (the best substrates were C7--C10 alcohols for one form and C10--C14 for the others). The two forms of ADH are probably isoenzymes of octanol dehydrogenase (EC 1.1.1.73). Cytosol of cells grown on n-alcane, had a reduced number of ADH forms. The data obtained are discussed in terms of the regulatory role of carbon and energy source (glucose or hexadecane) in the redistribution of alcohol dehydrogenases between structural components of cells (mitochondria) and cytosol.", "contents": "[Cytosolic alcohol dehydrogenases from yeast Torulopsis candida]. A comparative study of cell cytosol alcohol dehydrogenase (ADH) from yeast Torulopsis candida IBFM-Y-127 grown on glucose and hexadecane which were the only source of carbon, was made. In both cases ADH had a pH optimum within the range of 7.0--10.0, when various normal primary alcohols (C2--C16) were used. The enzyme was active only in the presence of NAD, which cannot be substituted by NADP. The total activity of ADH decreased approximately 8-fold when the length of hydrocarbon radicals was changed from C2 up to C16. When the cells were grown on hexadecane, only ethyl, n-buthyl, n-amyl and n-hexyl alcohols were active as substrates. The dehydration rate of each alcohol was far lower than that for the cytosol of glucose-grown cells. In the latter case the enzyme activity also decreased with an increase in the alcohol radical from C2 to C6. In all cases studied methyl alcohol and cyclic (cinnamyl alcohol--C8) alcohol were not dehydrated at all. Disc-electrophoresis in polyacrylamide gel, involving gel colouration for the assay of enzyme activity showed that glucose--grown cell cytosol contained three forms of ADH. One of those forms was highly active when short--chain normal primary alcohols were used; this form may be probably regarded as \"classical\" ADH (EC 1.1.1.1). The two other forms caused intensive dehydration of long-chain alcohols (the best substrates were C7--C10 alcohols for one form and C10--C14 for the others). The two forms of ADH are probably isoenzymes of octanol dehydrogenase (EC 1.1.1.73). Cytosol of cells grown on n-alcane, had a reduced number of ADH forms. The data obtained are discussed in terms of the regulatory role of carbon and energy source (glucose or hexadecane) in the redistribution of alcohol dehydrogenases between structural components of cells (mitochondria) and cytosol."}
{"id": "PMID:14730", "title": "[Human serum albumin: microheterogeneity and hemin-binding ability].", "content": "Microheterogeneity of human serum albumin was studied by isoelectric focussing in ampholines and the borax-borate buffer-mannite system within the pH range 4.0--6.0 and by fractional precipitation in 3 M KCl. Albumin was found to have the same degree of heterogeneity in all separating systems. However, during focussing in ampholines microheterogeneity is partially due to the albumin binding with the ampholines. In other systems similar binding was not observed. Studies of the albumin-hemin complex showed that different fractions bind hemin in a different degree, maximal binding being observed within the pH range of 5.0--5.2. Defatting does not affect the distribution of hemin within the fractions of serum albumin.", "contents": "[Human serum albumin: microheterogeneity and hemin-binding ability]. Microheterogeneity of human serum albumin was studied by isoelectric focussing in ampholines and the borax-borate buffer-mannite system within the pH range 4.0--6.0 and by fractional precipitation in 3 M KCl. Albumin was found to have the same degree of heterogeneity in all separating systems. However, during focussing in ampholines microheterogeneity is partially due to the albumin binding with the ampholines. In other systems similar binding was not observed. Studies of the albumin-hemin complex showed that different fractions bind hemin in a different degree, maximal binding being observed within the pH range of 5.0--5.2. Defatting does not affect the distribution of hemin within the fractions of serum albumin."}
{"id": "PMID:14731", "title": "[Nuclear ribonucleases and post-transcriptional changes of RNA. Specificity and other properties of rat liver nuclear endonuclease].", "content": "Some physico-chemical properties, specificity and the character of action of rat liver nuclear ribonuclease are studied. The enzyme maximal activity was observed at pH 7.5--8.0, ionic strength 0.02--0.3, Mg2+ being necessary. Nuclease is an oligomer, having molecular weight is 160000--180000 daltons and containing separate associates. Purified enzyme is free of contaminating activities (polynucleotidephosphorylase, DNAse; 5'-nucleotidase, and alkaline phosphatases). It is shown to hydrolyse polyA and RNA for endonuclease type, degradation products being oligonucleotides terminating with 5'-phosphate and 3'-hydroxyl groups. RNAse hydrolyses all phosphodiester bonds in polynucleotides, developing no specificity to the nature of bases. Relative hydrolysis rate for different substrates decreased as follows: polyA greater than yeast RNA greater than polyC greater than polyU greater than 28S rRNA greater than greater than 18S rRNA greater than polyA-polyU. The enzyme may be classified as ribonucleate-5'-nucleotidehydrolase (EC 3.1.4.9.).", "contents": "[Nuclear ribonucleases and post-transcriptional changes of RNA. Specificity and other properties of rat liver nuclear endonuclease]. Some physico-chemical properties, specificity and the character of action of rat liver nuclear ribonuclease are studied. The enzyme maximal activity was observed at pH 7.5--8.0, ionic strength 0.02--0.3, Mg2+ being necessary. Nuclease is an oligomer, having molecular weight is 160000--180000 daltons and containing separate associates. Purified enzyme is free of contaminating activities (polynucleotidephosphorylase, DNAse; 5'-nucleotidase, and alkaline phosphatases). It is shown to hydrolyse polyA and RNA for endonuclease type, degradation products being oligonucleotides terminating with 5'-phosphate and 3'-hydroxyl groups. RNAse hydrolyses all phosphodiester bonds in polynucleotides, developing no specificity to the nature of bases. Relative hydrolysis rate for different substrates decreased as follows: polyA greater than yeast RNA greater than polyC greater than polyU greater than 28S rRNA greater than greater than 18S rRNA greater than polyA-polyU. The enzyme may be classified as ribonucleate-5'-nucleotidehydrolase (EC 3.1.4.9.)."}
{"id": "PMID:14732", "title": "[Pterin-protein complex and ferredoxin as possible components of a molecular complex in photosystem I].", "content": "Properties are studied of pterin-protein complex (PPC), possible precursor of ferredoxin in electrone transport chain PS-I. PPC is shown to form chelate complex with Fe ions which are capable to activate the process of light reduction of NADP+ by chloroplasts in the absence of ferrodoxin. A possibility of dark reduction of NADP+ with the participation of light pre-activated PPC is found. Two-step scheme of electrone transport from P700 to ferredoxin is supposed. The data obtained indicate that one of sites of electrone transport into interior part of tilakoid is located on the reduction side of PS-I. An additional possibility of NADP+ reduction with the participation of PPC-Fe in vivo is suggested.", "contents": "[Pterin-protein complex and ferredoxin as possible components of a molecular complex in photosystem I]. Properties are studied of pterin-protein complex (PPC), possible precursor of ferredoxin in electrone transport chain PS-I. PPC is shown to form chelate complex with Fe ions which are capable to activate the process of light reduction of NADP+ by chloroplasts in the absence of ferrodoxin. A possibility of dark reduction of NADP+ with the participation of light pre-activated PPC is found. Two-step scheme of electrone transport from P700 to ferredoxin is supposed. The data obtained indicate that one of sites of electrone transport into interior part of tilakoid is located on the reduction side of PS-I. An additional possibility of NADP+ reduction with the participation of PPC-Fe in vivo is suggested."}
{"id": "PMID:14733", "title": "[Isolation and properties of cytoplasmic L(+)-lactatoxydase of Candida lipolytica yeasts].", "content": "The enzyme preparation of L(+)-lactatoxydase (K.F. 1.1.3.2) with molecular weight of 230 000 has been isolated from the soluble fraction of the C. lipolytica cells and purified similar 360 times. The enzyme oxydizes L(+)-lactate, the optimum activity of the enzyme being observed at pH 8.0. Oxydation of the substrate is followed by accumulation of H2O2. Silver ions, p-chloromercurybenzoate and dicumarol inhibit the activity of L(+)-lactatoxydase. Iron complexones, cyanide and L-malate do not inhibit oxydation of the substrate. Pyruvate and its fluorine derivative practically do not produce any inhibiting effects either. The enzyme preparation contains 0.6 moles of flavin and 2 moles of nonhaem iron per a mole of the enzyme. Km value for the substrate is equal to 4-10(-4) M, Vmax--4.5 mkatom O/min/mg. Acidation of incubation medium leads to a decrease both of Km and Vmax. Km value for oxygen is equal to 3.1 mkM O2. Beside oxygen, ferricyanide, 2.6-dichlorphenolindophenol, phenazine methosulphate and cytochrome C may also serve as acceptors of L(+)-lactatoxydase electrons. The oxydized enzyme preparation is characterized by a spectrum absorption maximum at 410 nm. Upon L(+)-lactatoxydase reduction the maximum is shifted up to 420 nm.", "contents": "[Isolation and properties of cytoplasmic L(+)-lactatoxydase of Candida lipolytica yeasts]. The enzyme preparation of L(+)-lactatoxydase (K.F. 1.1.3.2) with molecular weight of 230 000 has been isolated from the soluble fraction of the C. lipolytica cells and purified similar 360 times. The enzyme oxydizes L(+)-lactate, the optimum activity of the enzyme being observed at pH 8.0. Oxydation of the substrate is followed by accumulation of H2O2. Silver ions, p-chloromercurybenzoate and dicumarol inhibit the activity of L(+)-lactatoxydase. Iron complexones, cyanide and L-malate do not inhibit oxydation of the substrate. Pyruvate and its fluorine derivative practically do not produce any inhibiting effects either. The enzyme preparation contains 0.6 moles of flavin and 2 moles of nonhaem iron per a mole of the enzyme. Km value for the substrate is equal to 4-10(-4) M, Vmax--4.5 mkatom O/min/mg. Acidation of incubation medium leads to a decrease both of Km and Vmax. Km value for oxygen is equal to 3.1 mkM O2. Beside oxygen, ferricyanide, 2.6-dichlorphenolindophenol, phenazine methosulphate and cytochrome C may also serve as acceptors of L(+)-lactatoxydase electrons. The oxydized enzyme preparation is characterized by a spectrum absorption maximum at 410 nm. Upon L(+)-lactatoxydase reduction the maximum is shifted up to 420 nm."}
{"id": "PMID:14734", "title": "[The pH dependence of kinetic parameters of Penicillium brevicompactum RNAase].", "content": "The effect of pH on the kinetic parameters (Km and Ki) for extracellular acid Penicillium brevicompactum RNAse (pH max 4.7+/-0.1), non-specific to the chemical nature of nucleic bases, was studied. The pKm--pH dependence curve showed bends within the following intervals of pH: 3.5--4.0 and 5.6--6.0 (upward side concavity) and 6.2--6.8 (downward side concavity). The pKi--pH dependence for adenosine-3'-monophosphate as an inhibitor is identical to the pH dependence on pKm for the substrate. On the other hand, the pKi--pH dependence curves obtained for the base-free inhibitors (ribose-5'-monophosphate, or phosphate (adenosine) show no bends within the pH intervals of 3.0--4.0 and 5.6--7.0 respectively. A possibility is discussed of the presence of a carboxylic (pK 3.58+/-0.1) and two imidazole groups (pK 6.42+/-0.1--a weakly protonated and 5.8+/-+/-0.1--a strongly protonated group) in the RNAse active site and their participation in the formation of the RNAse-nucleotide (RNAse-substrate) complex.", "contents": "[The pH dependence of kinetic parameters of Penicillium brevicompactum RNAase]. The effect of pH on the kinetic parameters (Km and Ki) for extracellular acid Penicillium brevicompactum RNAse (pH max 4.7+/-0.1), non-specific to the chemical nature of nucleic bases, was studied. The pKm--pH dependence curve showed bends within the following intervals of pH: 3.5--4.0 and 5.6--6.0 (upward side concavity) and 6.2--6.8 (downward side concavity). The pKi--pH dependence for adenosine-3'-monophosphate as an inhibitor is identical to the pH dependence on pKm for the substrate. On the other hand, the pKi--pH dependence curves obtained for the base-free inhibitors (ribose-5'-monophosphate, or phosphate (adenosine) show no bends within the pH intervals of 3.0--4.0 and 5.6--7.0 respectively. A possibility is discussed of the presence of a carboxylic (pK 3.58+/-0.1) and two imidazole groups (pK 6.42+/-0.1--a weakly protonated and 5.8+/-+/-0.1--a strongly protonated group) in the RNAse active site and their participation in the formation of the RNAse-nucleotide (RNAse-substrate) complex."}
{"id": "PMID:14735", "title": "[Alkaline activation of myosin ATPase: some thermodynamic characteristics].", "content": "The increase in temperature leads to a decrease in pKa of the group responsible for the activation of CaATP2- hydrolysis by myosin in the alkaline zone of pH. At 20-25 degrees the pKa value is about 9. The value of ionization heat (deltaHi) calculated from pKa temperature dependence is 7.6+/-+/-0.8 kcal/mol. These values are approximated to the values known for phenol hydroxyl of tyrosine. It has been demonstrated that the acceleration of CaATP2- hydrolysis at alkaline values of pH is accompanied by an increase in the Arrhenius energy of activation (Ea), determined from the temperature dependence of the maximal reaction rate (V). The increase of Ea at alkaline values of pH is apparent and is due to an increase in the concentration of a deprotonized form of the enzyme, having a higher activity. A comparison of activation parameters of the reaction at alkaline and neutral values of pH permits to conclude that the acceleration of CaATP2- hydrolysis at alkaline values of pH is due to the acceleration of the limiting step of the reaction. It has also been found that at alkaline values of pH the power of myosin binding with ADP, a competitive inhibitor and the reaction product, is decreased. It is assumed that the acceleration of ATP hydrolysis at alkaline values of pH is due to accelerated dissociation of the reaction products from the active centre of the enzyme, as a result of ionization of a functional group of myosin, probably of the tyrosine residue.", "contents": "[Alkaline activation of myosin ATPase: some thermodynamic characteristics]. The increase in temperature leads to a decrease in pKa of the group responsible for the activation of CaATP2- hydrolysis by myosin in the alkaline zone of pH. At 20-25 degrees the pKa value is about 9. The value of ionization heat (deltaHi) calculated from pKa temperature dependence is 7.6+/-+/-0.8 kcal/mol. These values are approximated to the values known for phenol hydroxyl of tyrosine. It has been demonstrated that the acceleration of CaATP2- hydrolysis at alkaline values of pH is accompanied by an increase in the Arrhenius energy of activation (Ea), determined from the temperature dependence of the maximal reaction rate (V). The increase of Ea at alkaline values of pH is apparent and is due to an increase in the concentration of a deprotonized form of the enzyme, having a higher activity. A comparison of activation parameters of the reaction at alkaline and neutral values of pH permits to conclude that the acceleration of CaATP2- hydrolysis at alkaline values of pH is due to the acceleration of the limiting step of the reaction. It has also been found that at alkaline values of pH the power of myosin binding with ADP, a competitive inhibitor and the reaction product, is decreased. It is assumed that the acceleration of ATP hydrolysis at alkaline values of pH is due to accelerated dissociation of the reaction products from the active centre of the enzyme, as a result of ionization of a functional group of myosin, probably of the tyrosine residue."}
{"id": "PMID:14736", "title": "[Sulfhydryl groups of L-asparaginase A from Pseudomonas fluorescens AG].", "content": "It has been demonstrated that the activity of asparaginase A from Ps. fluorescens AG is completely inhibited by 10(-4) M p-chloromercurybenzoate and by 70-85% by Zn2+, Ca2+ and Cu2+ (2.10(-2) M). Iodoacetate, iodoacetamide, N-ethylimide of maleic acid and 5,5'-dithiobis-(2-nitrobenzoic acid) do not decrease the enzyme activity. Dithiothreitol and beta-mercaptoethanol reactivate the enzyme. L-asparagine, the substrate of asparaginase, protects the enzyme in a large degree against the inhibitory action of p-chloromercurybenzoate. p-chloromercurybenzoate induces a sharp increase in the asparaginase inactivation rate at acidic (6.5--5.5) and alkaline (7.5-8.5) values of pH. The enzyme modification by p-chloromercurybenzoate does not change the Km value for L-asparagine, but decreases Vmax. Thus it may be assumed, that asparaginase from Ps. fluorescens AG contains sulfhydryl groups essential for the enzyme activity.", "contents": "[Sulfhydryl groups of L-asparaginase A from Pseudomonas fluorescens AG]. It has been demonstrated that the activity of asparaginase A from Ps. fluorescens AG is completely inhibited by 10(-4) M p-chloromercurybenzoate and by 70-85% by Zn2+, Ca2+ and Cu2+ (2.10(-2) M). Iodoacetate, iodoacetamide, N-ethylimide of maleic acid and 5,5'-dithiobis-(2-nitrobenzoic acid) do not decrease the enzyme activity. Dithiothreitol and beta-mercaptoethanol reactivate the enzyme. L-asparagine, the substrate of asparaginase, protects the enzyme in a large degree against the inhibitory action of p-chloromercurybenzoate. p-chloromercurybenzoate induces a sharp increase in the asparaginase inactivation rate at acidic (6.5--5.5) and alkaline (7.5-8.5) values of pH. The enzyme modification by p-chloromercurybenzoate does not change the Km value for L-asparagine, but decreases Vmax. Thus it may be assumed, that asparaginase from Ps. fluorescens AG contains sulfhydryl groups essential for the enzyme activity."}
{"id": "PMID:14738", "title": "Effect of hypoxia on monoamine synthesis in brains of developing rats.", "content": "Tyrosine and tryptophan hydroxylase activity was studied in the postnatal rat brain in vivo by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan, respectively after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. With increasing age there was a significant increase in the amount of dopa and 5-HTP accumulated in the brain after administration of NSD 1015. After 30 min in a 12% oxygen environment there were significant reductions of tyrosine hydroxylase and tryptophan hydroxylase activity at 1,14 and 28 but not 4 days of postnatal age. Further, the decrease in 5-HTP accumulation was significantly more marked at 14 and 28 days than at 1 day of age. Thus, the oxygen-dependent synthesis of the neurotransmitter 5-hydroxytryptamine seems to be less vulnerable in the early postnatal rat brain.", "contents": "Effect of hypoxia on monoamine synthesis in brains of developing rats. Tyrosine and tryptophan hydroxylase activity was studied in the postnatal rat brain in vivo by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan, respectively after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. With increasing age there was a significant increase in the amount of dopa and 5-HTP accumulated in the brain after administration of NSD 1015. After 30 min in a 12% oxygen environment there were significant reductions of tyrosine hydroxylase and tryptophan hydroxylase activity at 1,14 and 28 but not 4 days of postnatal age. Further, the decrease in 5-HTP accumulation was significantly more marked at 14 and 28 days than at 1 day of age. Thus, the oxygen-dependent synthesis of the neurotransmitter 5-hydroxytryptamine seems to be less vulnerable in the early postnatal rat brain."}
{"id": "PMID:14740", "title": "Indication of the metarhodopsin I-II transition by absorption-changes of Eriochromblack T.", "content": "The dye eriochromblack T (erio T), added to an aqueous suspension of bovine retinal outer segments solubilized by digitonin, shows a light-induced absorption-increase at lambda = 645 nm. Erio T is shown to directly interact with miscellar metarhodopsin I and metarhodopsin II. The absorption-changes of erio T can be regarded as an indication of the transition from the metarhodopsin I conformation (with associated Ca2+) to the metarhodopsin II conformation (with associated H+).", "contents": "Indication of the metarhodopsin I-II transition by absorption-changes of Eriochromblack T. The dye eriochromblack T (erio T), added to an aqueous suspension of bovine retinal outer segments solubilized by digitonin, shows a light-induced absorption-increase at lambda = 645 nm. Erio T is shown to directly interact with miscellar metarhodopsin I and metarhodopsin II. The absorption-changes of erio T can be regarded as an indication of the transition from the metarhodopsin I conformation (with associated Ca2+) to the metarhodopsin II conformation (with associated H+)."}
{"id": "PMID:14743", "title": "Nonporous magnetic materials as enzyme supports: studies with immobilized chymotrypsin.", "content": "Chymotrypsin has been immobilized to several nonporous magnetic materials. Nickel particles were considered to be most suitable as immobilized enzyme supports. Chymotrypsin immobilized to nonporous magnetic supports was not fouled significantly by either whole milk or clarified yeast homogenate. AE-cellulose-chymotrypsin was rapidly fouled by both these materials and chymotrypsin immobilized to acrylic-based ion exchangers was slowly fouled. Immobilized enzyme activity was found to be inversely proportional to particle diameter for nonporous rock magnetic particles. Immobilization by adsorption and then glutaraldehyde crosslinking was used to produce controlled amounts of chymotrypsin on the particles. Esterolytic activity increased with enzyme loading but caseinolytic activity did not increase. Chymotrypsin is inhibited by metal ions from the magnetic supports. It is partially protected by use of a preliminary protein coating and may be reactivated by incubation with EDTA or BSA.", "contents": "Nonporous magnetic materials as enzyme supports: studies with immobilized chymotrypsin. Chymotrypsin has been immobilized to several nonporous magnetic materials. Nickel particles were considered to be most suitable as immobilized enzyme supports. Chymotrypsin immobilized to nonporous magnetic supports was not fouled significantly by either whole milk or clarified yeast homogenate. AE-cellulose-chymotrypsin was rapidly fouled by both these materials and chymotrypsin immobilized to acrylic-based ion exchangers was slowly fouled. Immobilized enzyme activity was found to be inversely proportional to particle diameter for nonporous rock magnetic particles. Immobilization by adsorption and then glutaraldehyde crosslinking was used to produce controlled amounts of chymotrypsin on the particles. Esterolytic activity increased with enzyme loading but caseinolytic activity did not increase. Chymotrypsin is inhibited by metal ions from the magnetic supports. It is partially protected by use of a preliminary protein coating and may be reactivated by incubation with EDTA or BSA."}
{"id": "PMID:14744", "title": "Chemically activated collagen for amyloglucosidase attachment. Use in a helicoidal reactor.", "content": "Amyloglucosidase was covalently bound to collagen sheets by a previously described method. The time of acidic methylation (first step of the collagen activation process) was important to obtain a good enzymatic surfacic activity. Homogeneity of the coupling procedure on the surface of collagen films was shown. Some properties of free enzyme were not affected after grafting; optimum pH and temperature, activation energy, and Km for maltose. Heat stability of the bound enzyme was slightly better; Km for soluble starch increased fivefold. In contrast, the maximal velocity in the presence of soluble starch remained four times that of maltose hydrolysis. Amyloglucosidase collagen membranes were used in a helicoidal reactor to produce glucose from maltose or soluble starch solutions. Tracer studies have shown that the helicoidal reactor behaved as a CSTR. The influence of maltose concentration and flow rate on conversion was studied and confirmed the absence of diffusional limitations for maltose. Recycling of concentrated solutions of maltose and soluble starch indicated strong diffusional restrictions for soluble starch. The catalytic support kept all its activity for 18 days continuous operation at 40 degrees C and 80% after 17 months storage at 4 degrees C.", "contents": "Chemically activated collagen for amyloglucosidase attachment. Use in a helicoidal reactor. Amyloglucosidase was covalently bound to collagen sheets by a previously described method. The time of acidic methylation (first step of the collagen activation process) was important to obtain a good enzymatic surfacic activity. Homogeneity of the coupling procedure on the surface of collagen films was shown. Some properties of free enzyme were not affected after grafting; optimum pH and temperature, activation energy, and Km for maltose. Heat stability of the bound enzyme was slightly better; Km for soluble starch increased fivefold. In contrast, the maximal velocity in the presence of soluble starch remained four times that of maltose hydrolysis. Amyloglucosidase collagen membranes were used in a helicoidal reactor to produce glucose from maltose or soluble starch solutions. Tracer studies have shown that the helicoidal reactor behaved as a CSTR. The influence of maltose concentration and flow rate on conversion was studied and confirmed the absence of diffusional limitations for maltose. Recycling of concentrated solutions of maltose and soluble starch indicated strong diffusional restrictions for soluble starch. The catalytic support kept all its activity for 18 days continuous operation at 40 degrees C and 80% after 17 months storage at 4 degrees C."}
{"id": "PMID:14745", "title": "A fermentation process for producing both ethanol and lysine-enriched yeast.", "content": "In 18 batch-fermentation experiments, baker's yeast was grown in an enriched mineral medium, containing 10% by weight glucose, at various pH and temperature levels. The pH and temperature are just two representative engineering variables which can be easily varied at negligible cost. The commercial yeast inoculum, 20% by weight or about .16% viable cells, was selected to represent industrial (nonsterile) conditions. Free L-lysine, ethanol, and cell growth were followed in time for each batch run held at a fixed pH and temperature. The maximum free lysine level reached at either 10 1/2 or 24 hr occurred at a pH of 5 and 32 degrees C. At 24 hr, the peak free lysine level, 120 mg/liter, is three times as great as the uncontrolled pH counterpart. In terms of total L-lysine (free plus protein-bound) the peak represents a 25% improvement over the uncontrolled case, based on an average 3.5% lysine level per cell weight. The greatest measured cell level, .9% by weight in the fermentation broth, or a 5 1/2-fold increase over th inoculum, was reached during the 36 degrees C and pH 3 run, while the largest measured ethanol value (3%, or 30% conversion by weight from glucose) was achieved during the 28 degrees C and pH 6 experiment. The optimal lysine  run product, however, no less than 15% of the maximum cell and 30% of the maximum ethanol levels.", "contents": "A fermentation process for producing both ethanol and lysine-enriched yeast. In 18 batch-fermentation experiments, baker's yeast was grown in an enriched mineral medium, containing 10% by weight glucose, at various pH and temperature levels. The pH and temperature are just two representative engineering variables which can be easily varied at negligible cost. The commercial yeast inoculum, 20% by weight or about .16% viable cells, was selected to represent industrial (nonsterile) conditions. Free L-lysine, ethanol, and cell growth were followed in time for each batch run held at a fixed pH and temperature. The maximum free lysine level reached at either 10 1/2 or 24 hr occurred at a pH of 5 and 32 degrees C. At 24 hr, the peak free lysine level, 120 mg/liter, is three times as great as the uncontrolled pH counterpart. In terms of total L-lysine (free plus protein-bound) the peak represents a 25% improvement over the uncontrolled case, based on an average 3.5% lysine level per cell weight. The greatest measured cell level, .9% by weight in the fermentation broth, or a 5 1/2-fold increase over th inoculum, was reached during the 36 degrees C and pH 3 run, while the largest measured ethanol value (3%, or 30% conversion by weight from glucose) was achieved during the 28 degrees C and pH 6 experiment. The optimal lysine  run product, however, no less than 15% of the maximum cell and 30% of the maximum ethanol levels."}
{"id": "PMID:14746", "title": "Production of Schardinger beta-dextrin by soluble and immobilized cyclodextrin glycosyltransferase of an alkalophilic Bacillus sp.", "content": "Succinylated cyclodextrin glycosyltransferase (EC 3.2.1.19) of an alkalophilic Bacillus sp. was adsorbed on a vinylpyridine copolymer. The enzyme had about 25% of the activity of soluble enzyme added. No increase of pH or thermal stability of the enzyme was observed by the adsorption, whereas optimum temperature for the enzyme action was shifted from 50 to 55 degrees C. The enzyme converted starch to cyclodextrine without significant loss of activity under the conditions of 4 times reusing of 6 hr conversion by the batch system or 2 weeks continuous reaction by the column system at 55 degrees C and pH 8.0. About 46% of the potato starch solution [15% (w/v)] was converted to cyclodextrins by the enzyme, and 52% was converted by the simultaneous action of the enzyme and alkaline pullulanase of alkalophilic Bacillus sp. (No. 202-1). These values were almost the same as those obtained by the soluble enzyme or enzymes system.", "contents": "Production of Schardinger beta-dextrin by soluble and immobilized cyclodextrin glycosyltransferase of an alkalophilic Bacillus sp. Succinylated cyclodextrin glycosyltransferase (EC 3.2.1.19) of an alkalophilic Bacillus sp. was adsorbed on a vinylpyridine copolymer. The enzyme had about 25% of the activity of soluble enzyme added. No increase of pH or thermal stability of the enzyme was observed by the adsorption, whereas optimum temperature for the enzyme action was shifted from 50 to 55 degrees C. The enzyme converted starch to cyclodextrine without significant loss of activity under the conditions of 4 times reusing of 6 hr conversion by the batch system or 2 weeks continuous reaction by the column system at 55 degrees C and pH 8.0. About 46% of the potato starch solution [15% (w/v)] was converted to cyclodextrins by the enzyme, and 52% was converted by the simultaneous action of the enzyme and alkaline pullulanase of alkalophilic Bacillus sp. (No. 202-1). These values were almost the same as those obtained by the soluble enzyme or enzymes system."}
{"id": "PMID:14747", "title": "Bacteriolysis by immobilized enzymes.", "content": "Bacteriolytic enzymes produced by Achromobacter lunatus were immobilized in collagen membrane. Intact bacteria such as Pseudomonas solanacearum, Xanthomonas oryzae, Staphylococcus aureus, and Pseudomonas aeruginosa were lyzed with the bacteriolytic enzyme-collagen membrane. Relative activity of the bacteriolytic enzyme-collagen membrane against Pseu. solanacearum was about 2% of that of native bacteriolytic enzymes. No difference in the optimum pH was observed between immobilized enzymes and native enzymes. The bacteriolytic enzymes in the collagen membrane were stable against sodium chloride which was an inhibitor of the native bacteriolytic enzymes. Xanthomonas oryzae and Pseu. aeruginosa were continuously lyzed by a reactor containing the rolled bacteriolytic enzyme-collagen membrane.", "contents": "Bacteriolysis by immobilized enzymes. Bacteriolytic enzymes produced by Achromobacter lunatus were immobilized in collagen membrane. Intact bacteria such as Pseudomonas solanacearum, Xanthomonas oryzae, Staphylococcus aureus, and Pseudomonas aeruginosa were lyzed with the bacteriolytic enzyme-collagen membrane. Relative activity of the bacteriolytic enzyme-collagen membrane against Pseu. solanacearum was about 2% of that of native bacteriolytic enzymes. No difference in the optimum pH was observed between immobilized enzymes and native enzymes. The bacteriolytic enzymes in the collagen membrane were stable against sodium chloride which was an inhibitor of the native bacteriolytic enzymes. Xanthomonas oryzae and Pseu. aeruginosa were continuously lyzed by a reactor containing the rolled bacteriolytic enzyme-collagen membrane."}
{"id": "PMID:14748", "title": "Aminoacylase pellets.", "content": "Aminoacylase was immobilized on the mycelium pellets of Aspergillus ochraceus by using albumin and glutaraldehyde. No difference in the optimum pH was observed between native aminoacylase and aminoacylase pellets. The aminoacylase pellets were stable in pH 4-8 but they were unstable in alkaline conditions. The aminoacylase pellets were more stable against heavy metal ions and inhibitors than native aminoacylase. However, the degree of the activation of aminoacylase with cobalt ion decreased with the immobilization. It was suggested that most of aminoacylase was covalently coupled to the mycelium with glutaraldehyde.", "contents": "Aminoacylase pellets. Aminoacylase was immobilized on the mycelium pellets of Aspergillus ochraceus by using albumin and glutaraldehyde. No difference in the optimum pH was observed between native aminoacylase and aminoacylase pellets. The aminoacylase pellets were stable in pH 4-8 but they were unstable in alkaline conditions. The aminoacylase pellets were more stable against heavy metal ions and inhibitors than native aminoacylase. However, the degree of the activation of aminoacylase with cobalt ion decreased with the immobilization. It was suggested that most of aminoacylase was covalently coupled to the mycelium with glutaraldehyde."}
{"id": "PMID:14749", "title": "Properties of enzymes immobilized by the diazotized m-diaminobenzene method.", "content": "Some properties of a number of enzymes immobilized by the diazotized m-diaminobenzene (dDAB) method are described. The pH-activity profiles of beta-D-glucosidase, glucoamylase, peroxidase, uricase, and D-glucose oxidase were virtually unchanged on immobilization while those of catalase and dextranase were significantly altered. beta-D-Glucosidase, glucoamylase, and glucose oxidase were found to be more susceptible to denaturation on lyophilization when immobilized than in the native state; however, sorbitol had a marked protective effect in every case examined. Sorbitol was also found to exert a stabilizing effect when lyophilized immobilized preparations were stored. Immobilization marginally improved the stabilities of a number of enzymes to heating at 60 degrees at pH 8.0. The usefulness for continuous reaction of a column of glucoamylase attached to celite was established. The reuse of the solid supports was demonstrated.", "contents": "Properties of enzymes immobilized by the diazotized m-diaminobenzene method. Some properties of a number of enzymes immobilized by the diazotized m-diaminobenzene (dDAB) method are described. The pH-activity profiles of beta-D-glucosidase, glucoamylase, peroxidase, uricase, and D-glucose oxidase were virtually unchanged on immobilization while those of catalase and dextranase were significantly altered. beta-D-Glucosidase, glucoamylase, and glucose oxidase were found to be more susceptible to denaturation on lyophilization when immobilized than in the native state; however, sorbitol had a marked protective effect in every case examined. Sorbitol was also found to exert a stabilizing effect when lyophilized immobilized preparations were stored. Immobilization marginally improved the stabilities of a number of enzymes to heating at 60 degrees at pH 8.0. The usefulness for continuous reaction of a column of glucoamylase attached to celite was established. The reuse of the solid supports was demonstrated."}
{"id": "PMID:14750", "title": "Characteristics of yeast invertase immobilized on porous cellulose beads.", "content": "Invertase from Candida utilis was immobilized on porous cellulose beads by an ionic-quanidino bond. The immobilized invertase showed optimum activity between pH 4.0 and 5.4, while the free enzyme had a sharp optimum at pH 4.1. Both temperature profiles were fairly similar up to 55 degrees C. However, above this temperature the immobilized enzyme was more stable than the free enzyme. From the temperature data, the activation energies were found to be 7,322 and 4,052 cal/g mol for the free and the immobilized enzyme, respectively. Candida invertase shows characteristics of substrate inhibition. Both the Km and Ki for the free and the immobilized enzymes were determined. The apparent Ki for the immobilized invertase was much higher than the Ki of the free enzyme, suggesting a diffusion effect. Immobilized invertase molecules deep in the pores only see sucrose concentrations much less than the bulk concentrations. Immobilization, thus, offers certain processing advantages in this regard.", "contents": "Characteristics of yeast invertase immobilized on porous cellulose beads. Invertase from Candida utilis was immobilized on porous cellulose beads by an ionic-quanidino bond. The immobilized invertase showed optimum activity between pH 4.0 and 5.4, while the free enzyme had a sharp optimum at pH 4.1. Both temperature profiles were fairly similar up to 55 degrees C. However, above this temperature the immobilized enzyme was more stable than the free enzyme. From the temperature data, the activation energies were found to be 7,322 and 4,052 cal/g mol for the free and the immobilized enzyme, respectively. Candida invertase shows characteristics of substrate inhibition. Both the Km and Ki for the free and the immobilized enzymes were determined. The apparent Ki for the immobilized invertase was much higher than the Ki of the free enzyme, suggesting a diffusion effect. Immobilized invertase molecules deep in the pores only see sucrose concentrations much less than the bulk concentrations. Immobilization, thus, offers certain processing advantages in this regard."}
{"id": "PMID:14751", "title": "One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation.", "content": "One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3-17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1-4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor.", "contents": "One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3-17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1-4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor."}
{"id": "PMID:14756", "title": "[Mucociliary function and its alteration by certain irritants (author's transl)].", "content": "Mucociliary clearance is usually estimated in vivo by the measurement of mucus transfer or by clearance of radio-active tracers previously deposited in the airways. These methods are relatively difficult and complex so that for routine studies measures are usually made of ciliary activity. To clarify the consequences of changes in activity the authors have established the relationship between the speed of mucus transport and the frequency of ciliary beating. From their own studies and from evidence in the literature they show how the clearance function of mucociliary activity can be disturbed by a fall in temperature and humidity, by viral infection, by atmospheric pollutants such as sulphur dioxide, nitrogen dioxide and aldehydes and by tobacco smoking. They indicate the beneficial effects obtained by the administration of beta adrenergic compounds and the limits of efficiency of mucolytic agents. They examined the pathophysiological consequences of the slowing down or arrest of mucus drainage with particular reference to the proliferation of infectious agents and their penetration into respiratory mucus membranes.", "contents": "[Mucociliary function and its alteration by certain irritants (author's transl)]. Mucociliary clearance is usually estimated in vivo by the measurement of mucus transfer or by clearance of radio-active tracers previously deposited in the airways. These methods are relatively difficult and complex so that for routine studies measures are usually made of ciliary activity. To clarify the consequences of changes in activity the authors have established the relationship between the speed of mucus transport and the frequency of ciliary beating. From their own studies and from evidence in the literature they show how the clearance function of mucociliary activity can be disturbed by a fall in temperature and humidity, by viral infection, by atmospheric pollutants such as sulphur dioxide, nitrogen dioxide and aldehydes and by tobacco smoking. They indicate the beneficial effects obtained by the administration of beta adrenergic compounds and the limits of efficiency of mucolytic agents. They examined the pathophysiological consequences of the slowing down or arrest of mucus drainage with particular reference to the proliferation of infectious agents and their penetration into respiratory mucus membranes."}
{"id": "PMID:14757", "title": "[La culture cellulaire en phase gazeuse. Un nouveau mod\u00e8le exp\u00e9rimental d'\u00e9tude in vitro des activit\u00e9s des macrophages alv\u00e9olaires].", "content": "Alveolar macrophages, collected by bronchopulmonary lavage and deposited on a membrane filter applied to the surface of a reservoir filled with nutrient medium, were maintained alive in direct contact with the atmosphere. Studies of morphology (using both optic and electron microscopy), of bactericidal activity and of ATP content confirmed the viability and vitality of the cell culture. This new experimental technique permits the in vitro reconstitution of the alveolar and bronchial microenvironment and offers a new method for the study of the cytotoxicity of toxic gases.", "contents": "[La culture cellulaire en phase gazeuse. Un nouveau mod\u00e8le exp\u00e9rimental d'\u00e9tude in vitro des activit\u00e9s des macrophages alv\u00e9olaires]. Alveolar macrophages, collected by bronchopulmonary lavage and deposited on a membrane filter applied to the surface of a reservoir filled with nutrient medium, were maintained alive in direct contact with the atmosphere. Studies of morphology (using both optic and electron microscopy), of bactericidal activity and of ATP content confirmed the viability and vitality of the cell culture. This new experimental technique permits the in vitro reconstitution of the alveolar and bronchial microenvironment and offers a new method for the study of the cytotoxicity of toxic gases."}
{"id": "PMID:14761", "title": "A simple and effective treatment for flight phobia.", "content": "Seventeen patients were treated by group desensitization and autohypnotic training over a period of six weeks for flight phobia, with a highly significant reduction of fear for the group. Expectation of benefit correlated positively with fear reduction.", "contents": "A simple and effective treatment for flight phobia. Seventeen patients were treated by group desensitization and autohypnotic training over a period of six weeks for flight phobia, with a highly significant reduction of fear for the group. Expectation of benefit correlated positively with fear reduction."}
{"id": "PMID:14762", "title": "Peptides with morphine-like action in the brain.", "content": "The reasons which led to the search in the brain for substances with morphine-like actions actions are discussed. Two pentapeptides, methionineenkephalin and leucine-enkephalin, were isolated. The amino acid sequence of methionine-enkephalin occurs also in the pituitary prohormone beta-lipotropin, of which longer fragments (endorphins) of up to 31 amino acids exhibit strong morphine-like action. The physiological significance of these short and long opioid peptides is discussed, particularly with regard to their possible roles as neurotransmitter or neuromodulator. With regard to the mechanisms involved in the development of tolerance to and dependence on opiates, the importance of interaction between the endogenous opioid peptides and the exogenous opiate alkaloids is stressed. The possible therapeutic implications are discussed briefly.", "contents": "Peptides with morphine-like action in the brain. The reasons which led to the search in the brain for substances with morphine-like actions actions are discussed. Two pentapeptides, methionineenkephalin and leucine-enkephalin, were isolated. The amino acid sequence of methionine-enkephalin occurs also in the pituitary prohormone beta-lipotropin, of which longer fragments (endorphins) of up to 31 amino acids exhibit strong morphine-like action. The physiological significance of these short and long opioid peptides is discussed, particularly with regard to their possible roles as neurotransmitter or neuromodulator. With regard to the mechanisms involved in the development of tolerance to and dependence on opiates, the importance of interaction between the endogenous opioid peptides and the exogenous opiate alkaloids is stressed. The possible therapeutic implications are discussed briefly."}
{"id": "PMID:14764", "title": "Drain-cover injuries in children.", "content": "This report highlights unnecessary injuries to the hands, forearms, and feet of small children, caused by falling drain-cover gratings, colloquially known as \"shores\". It is suggested that a simple locking device, similar to that employed on manhole covers, would eliminate this type of injury.", "contents": "Drain-cover injuries in children. This report highlights unnecessary injuries to the hands, forearms, and feet of small children, caused by falling drain-cover gratings, colloquially known as \"shores\". It is suggested that a simple locking device, similar to that employed on manhole covers, would eliminate this type of injury."}
{"id": "PMID:14767", "title": "The effect of a single dose of reserpine administered prior to incubation on the development of tyrosine hydroxylase activity in chick sympathetic ganglia.", "content": "A single dose of reserpine administered into the yolk sac of chicken eggs prior to incubation produces two distinct periods of significant increase in tyrosine hydroxylase (TH) activity over controls. The first period is 21 days of incubation (55%) and the second is between day 14 and 30 after hatching (a.h.) (69%). Cholineacetyltransferase (ChAc) and dopadecarboxylase (DDC) are not modified in the two periods of increased TH activity. Reserpine had no effect on cholinergic parasympathetic synapses and neurons in the ciliary ganglion, as judged by ChAc activity. When reserpine was acutely administered in three different posthatching periods only the injection at the latest period (days 26 and 27) caused a significant (38%) increase in TH activity at day 30. Postsynaptic nicotinic receptors were blocked selectively by injecting chlorisondamine in the chick starting at hatching for one week. The administration of chlorisondamine almost completely abolished the reserpine induced increase of TH activity at day 15 a.h. The present results support the view that the development of enzyme activities specifically related to neurotransmitter biosynthesis in chick autonomic ganglia is regulated not only by transsynaptic influences but also by regulatory inputs originating in the periphery.", "contents": "The effect of a single dose of reserpine administered prior to incubation on the development of tyrosine hydroxylase activity in chick sympathetic ganglia. A single dose of reserpine administered into the yolk sac of chicken eggs prior to incubation produces two distinct periods of significant increase in tyrosine hydroxylase (TH) activity over controls. The first period is 21 days of incubation (55%) and the second is between day 14 and 30 after hatching (a.h.) (69%). Cholineacetyltransferase (ChAc) and dopadecarboxylase (DDC) are not modified in the two periods of increased TH activity. Reserpine had no effect on cholinergic parasympathetic synapses and neurons in the ciliary ganglion, as judged by ChAc activity. When reserpine was acutely administered in three different posthatching periods only the injection at the latest period (days 26 and 27) caused a significant (38%) increase in TH activity at day 30. Postsynaptic nicotinic receptors were blocked selectively by injecting chlorisondamine in the chick starting at hatching for one week. The administration of chlorisondamine almost completely abolished the reserpine induced increase of TH activity at day 15 a.h. The present results support the view that the development of enzyme activities specifically related to neurotransmitter biosynthesis in chick autonomic ganglia is regulated not only by transsynaptic influences but also by regulatory inputs originating in the periphery."}
{"id": "PMID:14768", "title": "Responsiveness of neurones in the hippocampal region of anaesthetised and unanaesthetised cats to stimulation of sensory pathways.", "content": "The responses to sensory stimuli and to shocks to the optic pathways have been studied for 399 units in the hippocampal region of 19 cats. 172 units were recorded from anaesthetised cats and 229 from 7 unanaesthetised cats. In the unanaesthetised animals the proportions of units responding were high (60%) and did not differ significantly between regions for each type of stimulation investigated: visual, auditory and optic chiasma shocks. The proportion of units responsive to chiasmatic stimulation was related to the background firing rate. The latencies and duration of the responses were relatively long and variable. Both increases and decreases in responsiveness occurred. In a number of units response were erratic, sometimes being brisk and at other times totally absent. Responses during one series of stimuli were not always similar to those during a subsequent series. A higher proportion of units responded decrementally to a series of sensory stimuli than to a series of shocks to the optic chiasma. Movement by the animal was wihtout consistent effect on unit activity. Responses were markedly influenced according to whether or not the cat looked intently at an object. An important determinant of HR unit responses was the state of arousal, the effect being regionally distributed. In anaesthetised animals the proportions of responding units were substantially lower and the responses were weaker than those in the unanaesthetised cats.", "contents": "Responsiveness of neurones in the hippocampal region of anaesthetised and unanaesthetised cats to stimulation of sensory pathways. The responses to sensory stimuli and to shocks to the optic pathways have been studied for 399 units in the hippocampal region of 19 cats. 172 units were recorded from anaesthetised cats and 229 from 7 unanaesthetised cats. In the unanaesthetised animals the proportions of units responding were high (60%) and did not differ significantly between regions for each type of stimulation investigated: visual, auditory and optic chiasma shocks. The proportion of units responsive to chiasmatic stimulation was related to the background firing rate. The latencies and duration of the responses were relatively long and variable. Both increases and decreases in responsiveness occurred. In a number of units response were erratic, sometimes being brisk and at other times totally absent. Responses during one series of stimuli were not always similar to those during a subsequent series. A higher proportion of units responded decrementally to a series of sensory stimuli than to a series of shocks to the optic chiasma. Movement by the animal was wihtout consistent effect on unit activity. Responses were markedly influenced according to whether or not the cat looked intently at an object. An important determinant of HR unit responses was the state of arousal, the effect being regionally distributed. In anaesthetised animals the proportions of responding units were substantially lower and the responses were weaker than those in the unanaesthetised cats."}
{"id": "PMID:14769", "title": "Target organ regulation of sympathetic neuron development.", "content": "The role of target organs in the morphological and biochemical development of sympathetic neurons was examined in the neonatal rat. The superior cervical ganglion (SCG) and its end organs, the salivary glands and iris were employed as a model system. Unilateral sialectomy and iridectomy prevented the normal developmental increase in ipsilateral ganglion tyrosine hydroxylase (T-OH) activity, a marker for adrenergic maturation. Enzyme activity remained depressed by approximately 30% for at least 6 months, the longest time tested. Ganglion morphometry was performed to investigate the basis of the abnormal biochemical ontogeny. Target organ removal significantly decreased the number of adrenergic neurons in the Scg by approximately 30%. Total ganglion volume was reduced in a parallel fashion. Thus, end organ extirpation may prevent the biochemical maturation of the SCG by decreasing adrenergic neuron survival. Sialectomy without iridectomy prevented the normal postnatal increase in ganglion T-OH activity, but did not alter iris activity. These observations suggest that target removal prevents the development of only those neurons destined to innervate that organ. In addition to preventing normal adrenergic neuron ontogeny, target extirpation also prevented the normal development of presynaptic choline acetyltransferase activity. Presynaptic ganglion terminal may have failed to mature normally secondary to adrenergic destruction, or may have responded in some other manner to target organ extirpation.", "contents": "Target organ regulation of sympathetic neuron development. The role of target organs in the morphological and biochemical development of sympathetic neurons was examined in the neonatal rat. The superior cervical ganglion (SCG) and its end organs, the salivary glands and iris were employed as a model system. Unilateral sialectomy and iridectomy prevented the normal developmental increase in ipsilateral ganglion tyrosine hydroxylase (T-OH) activity, a marker for adrenergic maturation. Enzyme activity remained depressed by approximately 30% for at least 6 months, the longest time tested. Ganglion morphometry was performed to investigate the basis of the abnormal biochemical ontogeny. Target organ removal significantly decreased the number of adrenergic neurons in the Scg by approximately 30%. Total ganglion volume was reduced in a parallel fashion. Thus, end organ extirpation may prevent the biochemical maturation of the SCG by decreasing adrenergic neuron survival. Sialectomy without iridectomy prevented the normal postnatal increase in ganglion T-OH activity, but did not alter iris activity. These observations suggest that target removal prevents the development of only those neurons destined to innervate that organ. In addition to preventing normal adrenergic neuron ontogeny, target extirpation also prevented the normal development of presynaptic choline acetyltransferase activity. Presynaptic ganglion terminal may have failed to mature normally secondary to adrenergic destruction, or may have responded in some other manner to target organ extirpation."}
{"id": "PMID:14771", "title": "A comparative study of alkaline phosphatase in calcifying cartilage, odontoblasts and the enamel organ.", "content": "The enzyme alkaline phosphatase (AP) (EC 3.1.3.1) in three different calcification areas was studied by means of a spectrophotometric micro method using p-nitrophenylphosphate as a substrate. Rat maxillary incisor odontoblasts and enamel organ from the zones of matrix formation and maturation and tissue from rabbit metatarsal cartilage were allowed to react with the substrate in glycine-NaOH buffer at room temperature. The reaction was found to be linear for a minimum of 20 min. The pH optima for AP from these tissues were in the pH range of 10.0-10.3. In order to compare AP from the four calcification areas different parameters were studied. Heating at 56 degrees C or 60 degrees C for varying times revealed that the enzymes were almost completely inactivated after 10 min. Mg2+ ions activated the enzymes by about 25% at concentrations of 2.5 mM (enamel organ 1.25 mM); while only higher concentrations of Mg2+ had an inactivating effect, Ca2+ and PO3-4 ions were inactivating at varying concentrations. F- ions showed no effect on AP activity at concentrations below 250 mM (enamel organ 125 mM) but caused inactivation of the enzymes at about 50% at 1 M. EDTA was found to be a very effective AP inactivator at concentrations above 0.06 mM, whereas urea did not noticeably affect the enzyme reactions at concentrations below 1 M. At higher concentrations, inactivation was observed. In order to determine AP localization in the epiphyseal plate successive 40-mum-thick, freeze-sectioned slices were analyzed. The activity was highest nearest the zone of cartilage calcification and decreased towards the reserve cell zone. It was concluded that the same AP isoenzyme is present in these quite different calcification loci.", "contents": "A comparative study of alkaline phosphatase in calcifying cartilage, odontoblasts and the enamel organ. The enzyme alkaline phosphatase (AP) (EC 3.1.3.1) in three different calcification areas was studied by means of a spectrophotometric micro method using p-nitrophenylphosphate as a substrate. Rat maxillary incisor odontoblasts and enamel organ from the zones of matrix formation and maturation and tissue from rabbit metatarsal cartilage were allowed to react with the substrate in glycine-NaOH buffer at room temperature. The reaction was found to be linear for a minimum of 20 min. The pH optima for AP from these tissues were in the pH range of 10.0-10.3. In order to compare AP from the four calcification areas different parameters were studied. Heating at 56 degrees C or 60 degrees C for varying times revealed that the enzymes were almost completely inactivated after 10 min. Mg2+ ions activated the enzymes by about 25% at concentrations of 2.5 mM (enamel organ 1.25 mM); while only higher concentrations of Mg2+ had an inactivating effect, Ca2+ and PO3-4 ions were inactivating at varying concentrations. F- ions showed no effect on AP activity at concentrations below 250 mM (enamel organ 125 mM) but caused inactivation of the enzymes at about 50% at 1 M. EDTA was found to be a very effective AP inactivator at concentrations above 0.06 mM, whereas urea did not noticeably affect the enzyme reactions at concentrations below 1 M. At higher concentrations, inactivation was observed. In order to determine AP localization in the epiphyseal plate successive 40-mum-thick, freeze-sectioned slices were analyzed. The activity was highest nearest the zone of cartilage calcification and decreased towards the reserve cell zone. It was concluded that the same AP isoenzyme is present in these quite different calcification loci."}
{"id": "PMID:14772", "title": "Buprenorphine hydrochloride: determination of analgesic potency.", "content": "An open evaluation of relief from severe pain following major abdominal operations was carried out on at least ten patients, who had given written consent, with 0.1 to 0.4 mg doses of buprenorphine hydrochloride administered intramuscularly. Statistical analysis of the data showed that 0.3 mg of this compound provided quite satisfactory relief from pain for up to six hours. Seven more consenting patients were given buprenorphine hydrochloride 0.5 to 0.6 mg, but they did not receive much greater or longer pain relief than those receiving 0.3 to 0.4 mg. However, the latter patients were younger and heavier. It was concluded that buprenorphine hydrochloride 0.2 to 0.4 mg provided relief of severe pain probably as well as is observed with morphine 10 mg for the average-size patient, but the duration of pain relief with the new compound is substantially longer than with other strong analgesics previously tested. The only common side effect noted was drowsiness, which was observed during the analgesic action of the compound. No appreciable alterations were seen in the respiration, pulse rate and blood pressure. On the basis of these tests, buprenorphine hydrochloride appears to be a satisfactory analgesic for severe postoperative pain, and it deserves extensive study.", "contents": "Buprenorphine hydrochloride: determination of analgesic potency. An open evaluation of relief from severe pain following major abdominal operations was carried out on at least ten patients, who had given written consent, with 0.1 to 0.4 mg doses of buprenorphine hydrochloride administered intramuscularly. Statistical analysis of the data showed that 0.3 mg of this compound provided quite satisfactory relief from pain for up to six hours. Seven more consenting patients were given buprenorphine hydrochloride 0.5 to 0.6 mg, but they did not receive much greater or longer pain relief than those receiving 0.3 to 0.4 mg. However, the latter patients were younger and heavier. It was concluded that buprenorphine hydrochloride 0.2 to 0.4 mg provided relief of severe pain probably as well as is observed with morphine 10 mg for the average-size patient, but the duration of pain relief with the new compound is substantially longer than with other strong analgesics previously tested. The only common side effect noted was drowsiness, which was observed during the analgesic action of the compound. No appreciable alterations were seen in the respiration, pulse rate and blood pressure. On the basis of these tests, buprenorphine hydrochloride appears to be a satisfactory analgesic for severe postoperative pain, and it deserves extensive study."}
{"id": "PMID:14773", "title": "Rapid intubation with fazadinium and suxamethonium.", "content": "Fazadinium at two dose levels (1 mg/kg and 1.5 mg/kg) and suxamethonium at three dose levels (50 mg, 75 mg and 100 mg) were investigated in 106 adult patients to determine the time interval from injection to tracheal intubation. The intubating conditions were graded according to the scheme described by Lund and Stovner. Suxamethonium 100 mg gave the shortest time interval between the end of injection and intubation. There was no significant difference between the intubation time when smaller doses of suxamethonium (50 mg and 75 mg were used and those when AH8165 (1 mg and 1.5 mg/kg) were given. Suxamethonium 100 mg also produced a significantly higher incidence of excellent intubating conditions. The clinical implications of the findings are discussed.", "contents": "Rapid intubation with fazadinium and suxamethonium. Fazadinium at two dose levels (1 mg/kg and 1.5 mg/kg) and suxamethonium at three dose levels (50 mg, 75 mg and 100 mg) were investigated in 106 adult patients to determine the time interval from injection to tracheal intubation. The intubating conditions were graded according to the scheme described by Lund and Stovner. Suxamethonium 100 mg gave the shortest time interval between the end of injection and intubation. There was no significant difference between the intubation time when smaller doses of suxamethonium (50 mg and 75 mg were used and those when AH8165 (1 mg and 1.5 mg/kg) were given. Suxamethonium 100 mg also produced a significantly higher incidence of excellent intubating conditions. The clinical implications of the findings are discussed."}
{"id": "PMID:14774", "title": "Characterization of the interaction between chymotrypsin and heparin.", "content": "Heparin forms a complex with chymotrypsin which is active towards glutaryl-L-phenylalanine-p-nitroanilide (GPANA) and glutaryl-L-phenylalanine-beta-naphthylamide (GPNA) at pH 7.6. The activity of chymotrypsin towards GPANA at pH 7.6 is enhanced in the presence of heparin. Heparin does not bind at the active site of the enzyme since proflavin is not displaced from the active site of chymotrypsin upon complex formation. The heparin-chymotrypsin complex migrates under basic polyacrylamide disc gel electrophoresis conditions to a position intermediate between heparin and free chymotrypsin. The complex is dissociable under acidic polyacrylamide gel electrophoresis conditions. It is estimated that one to three molecules of heparin can bind to each chymotrypsin molecule on the basis of electrophoretic and enzymic activity data.", "contents": "Characterization of the interaction between chymotrypsin and heparin. Heparin forms a complex with chymotrypsin which is active towards glutaryl-L-phenylalanine-p-nitroanilide (GPANA) and glutaryl-L-phenylalanine-beta-naphthylamide (GPNA) at pH 7.6. The activity of chymotrypsin towards GPANA at pH 7.6 is enhanced in the presence of heparin. Heparin does not bind at the active site of the enzyme since proflavin is not displaced from the active site of chymotrypsin upon complex formation. The heparin-chymotrypsin complex migrates under basic polyacrylamide disc gel electrophoresis conditions to a position intermediate between heparin and free chymotrypsin. The complex is dissociable under acidic polyacrylamide gel electrophoresis conditions. It is estimated that one to three molecules of heparin can bind to each chymotrypsin molecule on the basis of electrophoretic and enzymic activity data."}
{"id": "PMID:14775", "title": "Isolation and properties of a ferredoxin from leaves of Sambucus racemosa L.", "content": "Ferredoxin was isolated in good yield from leaves of Sambucus racemosa L. by the following procedure: (1) homogenization in buffered acetone-water (1:1v/v); (2) ion-exchange chromatography on several columns of DEAE-cellulose; and (3) purification by gel filtration with Sephadex G-75. The ultraviolet and visible spectrum showed maxima at 277, 331, 423, and 466 nm. The electron paramagnetic resonance spectrum was centered around g = 1.957. The protein sustained an initial photoreduction rate of 86 mumol NADP per milligram chlorophyll per hour. The amino acid composition was found to be Lys 5, His 2, Arg1, Asx11, Thr5, Ser7, Glx17, Pro6, Gly7, Ala6-7, Cys4, Val8, Ile5, Leu7, Tyr3, Phe2, and Trp1. The molecule had a molecular weight of 10 700 and contained two atoms of iron. The amino-terminal residue was alanine. These properties are highly similar to those of other angiosperm ferredoxins. Sambucus ferredoxin was found to be most closely related to that of Leucaena.", "contents": "Isolation and properties of a ferredoxin from leaves of Sambucus racemosa L. Ferredoxin was isolated in good yield from leaves of Sambucus racemosa L. by the following procedure: (1) homogenization in buffered acetone-water (1:1v/v); (2) ion-exchange chromatography on several columns of DEAE-cellulose; and (3) purification by gel filtration with Sephadex G-75. The ultraviolet and visible spectrum showed maxima at 277, 331, 423, and 466 nm. The electron paramagnetic resonance spectrum was centered around g = 1.957. The protein sustained an initial photoreduction rate of 86 mumol NADP per milligram chlorophyll per hour. The amino acid composition was found to be Lys 5, His 2, Arg1, Asx11, Thr5, Ser7, Glx17, Pro6, Gly7, Ala6-7, Cys4, Val8, Ile5, Leu7, Tyr3, Phe2, and Trp1. The molecule had a molecular weight of 10 700 and contained two atoms of iron. The amino-terminal residue was alanine. These properties are highly similar to those of other angiosperm ferredoxins. Sambucus ferredoxin was found to be most closely related to that of Leucaena."}
{"id": "PMID:14776", "title": "NADPH-dependent lipid peroxidation and its effects on aminopyrine N-demethylation in subcellular fractions of human neonatal liver.", "content": "NADPH-dependent lipid peroxidation was determined in humans, using subcellular fractions of livers obtained from newborn infants. As reported for other species, activity was concentrated in the microsomal fraction and was similar to that found in the rat. High activity of lipid peroxidation induced by iron decreased aminopyrine N-demethylation and slightly reduced linearity time for the reaction. Compared with the rat, however, human microsomes were more resistant to the effects of lipid peroxidation. If liped peroxidation occurs in vivo it is unlikely to affect drug oxidation to any great degree in human infants.", "contents": "NADPH-dependent lipid peroxidation and its effects on aminopyrine N-demethylation in subcellular fractions of human neonatal liver. NADPH-dependent lipid peroxidation was determined in humans, using subcellular fractions of livers obtained from newborn infants. As reported for other species, activity was concentrated in the microsomal fraction and was similar to that found in the rat. High activity of lipid peroxidation induced by iron decreased aminopyrine N-demethylation and slightly reduced linearity time for the reaction. Compared with the rat, however, human microsomes were more resistant to the effects of lipid peroxidation. If liped peroxidation occurs in vivo it is unlikely to affect drug oxidation to any great degree in human infants."}
{"id": "PMID:14777", "title": "Flow rates of components in digesta of pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum, and fed semipurified, hard wheat, and soft wheat diets.", "content": "Four pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum were used to study flow rates of total digesta, insoluble dry matter, nitrogen, and amino acids entering and leaving the small intestine. The pigs received a semipurified diet, a hard wheat diet, or a soft wheat diet. These were approximately isonitrogenous. A higher rate of passage of digesta through the proximal duodenum and terminal ileum were measured in pigs receiving the hard wheat diet. Peak flow of digesta at the duodenum of all pigs occurred at 1 h post feeding. Peak flow of digesta at the ileum occurred at 9 h post feeding on the soft wheat diet, but somewhat earlier on the hard wheat and semipurified diet. More nitrogen and essential amino acids flowed in the solid fraction of duodenal digesta during the first 2 h post feeding for the wheat diets and 4 h post feeding for the semipurified diet. It was concluded that flow rate of most nutrients from the stomach and through the small intestine of pigs is modified by the composition and texture of the food ingested. It is postulated that efficiency of mixing of digesta with digestive secretions in the stomach is a major factor influencing rate of flow.", "contents": "Flow rates of components in digesta of pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum, and fed semipurified, hard wheat, and soft wheat diets. Four pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum were used to study flow rates of total digesta, insoluble dry matter, nitrogen, and amino acids entering and leaving the small intestine. The pigs received a semipurified diet, a hard wheat diet, or a soft wheat diet. These were approximately isonitrogenous. A higher rate of passage of digesta through the proximal duodenum and terminal ileum were measured in pigs receiving the hard wheat diet. Peak flow of digesta at the duodenum of all pigs occurred at 1 h post feeding. Peak flow of digesta at the ileum occurred at 9 h post feeding on the soft wheat diet, but somewhat earlier on the hard wheat and semipurified diet. More nitrogen and essential amino acids flowed in the solid fraction of duodenal digesta during the first 2 h post feeding for the wheat diets and 4 h post feeding for the semipurified diet. It was concluded that flow rate of most nutrients from the stomach and through the small intestine of pigs is modified by the composition and texture of the food ingested. It is postulated that efficiency of mixing of digesta with digestive secretions in the stomach is a major factor influencing rate of flow."}
{"id": "PMID:14778", "title": "Evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose.", "content": "Release of endogenous amino acids labelled via D-[U-14C]glucose was compared with that of several exogenous labelled amino acids using slices of guinea pig cerebral cortex. Electrical field stimulation evoked a selective release of endogenous [14C]glutamate, [14C]aspartate, and gamma-amino[14C]butyrate (14C-labelled GABA). The selectivity of release correlated well with 14C incorporation into endogenous amino acids. Calculations of the fraction of the tissue radioactivity released indicated that the selectivity was not an artifact due to differential incorporation. Because glucose in mammalian brain is metabolized almost entirely by the so-called 'large compartment', it is tentatively concluded that the releasable 'transmitter pool' of glutamate, aspartate, and GABA is located in this 'large compartment'.", "contents": "Evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose. Release of endogenous amino acids labelled via D-[U-14C]glucose was compared with that of several exogenous labelled amino acids using slices of guinea pig cerebral cortex. Electrical field stimulation evoked a selective release of endogenous [14C]glutamate, [14C]aspartate, and gamma-amino[14C]butyrate (14C-labelled GABA). The selectivity of release correlated well with 14C incorporation into endogenous amino acids. Calculations of the fraction of the tissue radioactivity released indicated that the selectivity was not an artifact due to differential incorporation. Because glucose in mammalian brain is metabolized almost entirely by the so-called 'large compartment', it is tentatively concluded that the releasable 'transmitter pool' of glutamate, aspartate, and GABA is located in this 'large compartment'."}
{"id": "PMID:14779", "title": "Ca2+-dependence of the evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose.", "content": "Spontaneous and electrically evoked release of exogenous labelled amino acids and endogenous amino acids labelled from D-[U-14C]glucose were compared in control and Ca2+-free medium using guinea pig cerebral cortex slices. Spontaneous release of all labelled amino acids, except that of endogenous 14C-labelled threonine-serine-glutamine (unseparated) and exogenous [14C]aspartate, was doubled in Ca2+-free medium. The major portion of the electrically evoked release of endogenous [14C]glutamate, [14C]aspartate, gamma-amino[14C]butyrate (14C-labelled GABA) and exogenous 3H-labelled GABA was Ca2+-inpendent. More than half of the evoked release of the other labelled amino acids was Ca2+-independent. As the pattern of Ca2+-dependence of the evoked release concurred with the selectivity of the evoked release for endogenous [14C]-glutamate, [14C]aspartate, and 14C-labelled GABA, it was concluded that these labelled amino acids were probably released from the amino acid 'transmitter pool'.", "contents": "Ca2+-dependence of the evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose. Spontaneous and electrically evoked release of exogenous labelled amino acids and endogenous amino acids labelled from D-[U-14C]glucose were compared in control and Ca2+-free medium using guinea pig cerebral cortex slices. Spontaneous release of all labelled amino acids, except that of endogenous 14C-labelled threonine-serine-glutamine (unseparated) and exogenous [14C]aspartate, was doubled in Ca2+-free medium. The major portion of the electrically evoked release of endogenous [14C]glutamate, [14C]aspartate, gamma-amino[14C]butyrate (14C-labelled GABA) and exogenous 3H-labelled GABA was Ca2+-inpendent. More than half of the evoked release of the other labelled amino acids was Ca2+-independent. As the pattern of Ca2+-dependence of the evoked release concurred with the selectivity of the evoked release for endogenous [14C]-glutamate, [14C]aspartate, and 14C-labelled GABA, it was concluded that these labelled amino acids were probably released from the amino acid 'transmitter pool'."}
{"id": "PMID:14780", "title": "Effects of saline infusion and acute metabolic acidosis and alkalosis on water and electrolyte transport in the human colon.", "content": "Both the kidney and colon secrete bicarbonate and transport water and electrolytes. The respective contributions of these two organs to acid-base and electrolyte balance in normal man has thus been studied in eight healthy male volunteers who underwent simultaneous renal clearance studies, and colonic perfusion with a 0.9% saline or 7.2% mannitol solution, during metabolic alkalosis and acidosis, extracellular volume expansion, and control conditions. There was no influence of these acid-base conditions on electrolyte transport in the colon. In the urine, preferential loss of chloride over sodium averaged 81, 143 (P less than 0.001), and 141 (P less than 0.05) muequiv./min, during control, metabolic acidosis, and extracellular volume expansion conditions, respectively. During alkalosis more sodium than chloride was lost (146 muequiv./min) (P less than 0.001). Colonic pH averaged 7.41 during saline and 6.75 (P less than 0.005) during mannitol perfusion. Titratable acid was not produced in the colon during saline perfusion, and averaged 18 muequiv./min during mannitol perfusion. Urinary titratable acid increased from 19 to 25 muequiv./min (P less than 0.01) during volume expansion. With saline perfusion, bicarbonate secretion rate in the colon rose from 249 muequiv./min during control conditions to 289 muequiv./min during metabolic alkalosis (P less than 0.05). More bicarbonate was excreted in the urine during alkalosis when mannitol was introduced in the colon (243 muequiv./min) than when saline was perfused (152 muequiv./min) (P less than 0.05). This study indicates that the response of the human colon is trivial compared with that of the kidney during acute changes in acid-base balance.", "contents": "Effects of saline infusion and acute metabolic acidosis and alkalosis on water and electrolyte transport in the human colon. Both the kidney and colon secrete bicarbonate and transport water and electrolytes. The respective contributions of these two organs to acid-base and electrolyte balance in normal man has thus been studied in eight healthy male volunteers who underwent simultaneous renal clearance studies, and colonic perfusion with a 0.9% saline or 7.2% mannitol solution, during metabolic alkalosis and acidosis, extracellular volume expansion, and control conditions. There was no influence of these acid-base conditions on electrolyte transport in the colon. In the urine, preferential loss of chloride over sodium averaged 81, 143 (P less than 0.001), and 141 (P less than 0.05) muequiv./min, during control, metabolic acidosis, and extracellular volume expansion conditions, respectively. During alkalosis more sodium than chloride was lost (146 muequiv./min) (P less than 0.001). Colonic pH averaged 7.41 during saline and 6.75 (P less than 0.005) during mannitol perfusion. Titratable acid was not produced in the colon during saline perfusion, and averaged 18 muequiv./min during mannitol perfusion. Urinary titratable acid increased from 19 to 25 muequiv./min (P less than 0.01) during volume expansion. With saline perfusion, bicarbonate secretion rate in the colon rose from 249 muequiv./min during control conditions to 289 muequiv./min during metabolic alkalosis (P less than 0.05). More bicarbonate was excreted in the urine during alkalosis when mannitol was introduced in the colon (243 muequiv./min) than when saline was perfused (152 muequiv./min) (P less than 0.05). This study indicates that the response of the human colon is trivial compared with that of the kidney during acute changes in acid-base balance."}
{"id": "PMID:14781", "title": "Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy.", "content": "Pregnant mice were given a single dose (10 mug/g body weight) of diethylstilbestrol (DES) on Days 7 to 19, which correspond to the first to fifth lunar months in humans, after the authors, using a 14C-labeled compound, confirmed easy placental penetration by DES. Treatment with DES on Days 15 to 19 resulted in the induction of persistent urogenital sinus (15.8 to 92.5%) and hypertrophy of the portio vaginalis (11.8 to 73.3%) in female offspring, and treatment on Days 17 and 19 resulted in the induction of undescended testes and their hypogenesis (70.4 to 73.3%) in male offspring, although treatment with DES at other stages of pregnancy and after birth did not cause these alterations. The incidence of various tumors (lung adenoma, granulosa cell tumor, etc.) increased significantly (31.0 to 37.9%) when DES was given on Days 15 and 17, which correspond to the stage sensitive to other carcinogens. However, adenosis and adenocarcinoma of the vagina were not observed in the offspring.", "contents": "Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy. Pregnant mice were given a single dose (10 mug/g body weight) of diethylstilbestrol (DES) on Days 7 to 19, which correspond to the first to fifth lunar months in humans, after the authors, using a 14C-labeled compound, confirmed easy placental penetration by DES. Treatment with DES on Days 15 to 19 resulted in the induction of persistent urogenital sinus (15.8 to 92.5%) and hypertrophy of the portio vaginalis (11.8 to 73.3%) in female offspring, and treatment on Days 17 and 19 resulted in the induction of undescended testes and their hypogenesis (70.4 to 73.3%) in male offspring, although treatment with DES at other stages of pregnancy and after birth did not cause these alterations. The incidence of various tumors (lung adenoma, granulosa cell tumor, etc.) increased significantly (31.0 to 37.9%) when DES was given on Days 15 and 17, which correspond to the stage sensitive to other carcinogens. However, adenosis and adenocarcinoma of the vagina were not observed in the offspring."}
{"id": "PMID:14782", "title": "Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes.", "content": "Extracts of human normal and leukemic leukocytes contain an enzyme that catalyzes a transfer of labeled methyl carbon from N5-[14C]methyltetrahydrofolate to tryptamine. Evidence is presented that this reaction is not attributable to a methyltransferase but to the following reaction sequence: (a) an oxidation of N5-[14C]methyltetrahydrofolate to N5, N10-[14C]methylenetetrahydrofolate that is catalyzed by N5, N10-methylenetetrahydrofolate reductase (EC 1.1.1.68); (b) spontaneous release of [14C]formaldehyde from N5, N10-[14C]methylenetetrahydrofolate; and (c) nonenzymatic condensation of [14C]formaldehyde with tryptamine to form a radioactive carboline derivative. The occurrence of this sequence in leukocytes is suggested by data that show that the enzyme reaction is strongly stimulated by addition of flavin adenine dinucleotide and that the final product is chromatographically identical to the adduct formed in the reaction of [14C]formaldehyde with tryptamine. In the absence of tryptamine, a product accumulates that can react with other HCHO acceptors, i.e., beta-phenylethylamine and dimedone; another reaction product is tetrahydrofolate. Production of formaldehyde is relatively more active in normal lymphocytes than in normal granulocytes, but it is even higher in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Formaldehyde production in leukocytes is only slightly stimulated by addition of various cobalamins, and activity is normal in leukocytes from a vitamin B12-deficient patient. We conclude that the system is cobalamin independent. Thus, there exists an active pathway from N5-methyltetrahydrofolate to tetrahydrofolate other than the one catalyzed by cobalamin-dependent N5-methyltetrahydrofolate-homocysteine methyltransferase.", "contents": "Production of formaldehyde from N5-methyltetrahydrofolate by normal and leukemic leukocytes. Extracts of human normal and leukemic leukocytes contain an enzyme that catalyzes a transfer of labeled methyl carbon from N5-[14C]methyltetrahydrofolate to tryptamine. Evidence is presented that this reaction is not attributable to a methyltransferase but to the following reaction sequence: (a) an oxidation of N5-[14C]methyltetrahydrofolate to N5, N10-[14C]methylenetetrahydrofolate that is catalyzed by N5, N10-methylenetetrahydrofolate reductase (EC 1.1.1.68); (b) spontaneous release of [14C]formaldehyde from N5, N10-[14C]methylenetetrahydrofolate; and (c) nonenzymatic condensation of [14C]formaldehyde with tryptamine to form a radioactive carboline derivative. The occurrence of this sequence in leukocytes is suggested by data that show that the enzyme reaction is strongly stimulated by addition of flavin adenine dinucleotide and that the final product is chromatographically identical to the adduct formed in the reaction of [14C]formaldehyde with tryptamine. In the absence of tryptamine, a product accumulates that can react with other HCHO acceptors, i.e., beta-phenylethylamine and dimedone; another reaction product is tetrahydrofolate. Production of formaldehyde is relatively more active in normal lymphocytes than in normal granulocytes, but it is even higher in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Formaldehyde production in leukocytes is only slightly stimulated by addition of various cobalamins, and activity is normal in leukocytes from a vitamin B12-deficient patient. We conclude that the system is cobalamin independent. Thus, there exists an active pathway from N5-methyltetrahydrofolate to tetrahydrofolate other than the one catalyzed by cobalamin-dependent N5-methyltetrahydrofolate-homocysteine methyltransferase."}
{"id": "PMID:14783", "title": "Suppression of antibody-mediated and cell-mediated murine immunity by the carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide.", "content": "N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide (NFTA) administered at 1000 ppm in diet to mice for 12 weeks induced a high incidence of lymphocytic leukemia. Effects of NFTA on antibody-mediated immunity and cell-mediated immunity of BALB/c mice were studied using the spleen plaque assay for detection of immunoglobulin M-producing cells and the graft-versus-host (GVH) reaction, respectively. NFTA suppressed both responses. With the spleen plaque assay, the number of antibody-forming cells (AFC) to sheep red blood cells was significantly less than in unmedicated, control mice after treated mice received NFTA at 1000 ppm for 6 days. The GVH reaction was not suppressed at 21 days, but was severely suppressed at 70 days, prior to the histological appearance of leukemia. Effect of dose was studied by administering NFTA at 100, 250, 500, and 1000 ppm of diet for 13 to 14 weeks and then determining the response in the spleen plaque assay and GVH reactions. The ratio of AFC/spleen of NFTA-treated groups to AFC/spleen of an unmedicated control group, at the above specified doses, was 0.86, 0.22, 0.33, and 0.54 in ascending dosage order beginning with 100 ppm. For the GVH reaction, the suppression of the cell-mediated immunity was directly proportional to the dose of NFTA. Suppression of the antibody-mediated immunity in relation to the induction of leukemia at 28 weeks was studied by feeding NFTA at 500 ppm for 14 weeks, followed by unmedicated diet for 14 weeks. During the 11th week, mice were immunized with SRBC; 5 days later the spleens were removed and the spleen plaque assay was performed. Eight of 18 mice fed NFTA developed leukemia. The number of AFC/spleen was 78 X 10(3) +/- 34 for those with leukemia and 68 X 10(3) +/- 24 (p greater than 0.5) for those without leukemia, compared with 170 X 10(3) +/- 74 for the control mice (p less than 0.01 for both groups, compared with controls). A closely related carcinogenic nitrofuran, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, did not suppress the antibody-mediated immunity response measured during the 11th week of administration.", "contents": "Suppression of antibody-mediated and cell-mediated murine immunity by the carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide. N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide (NFTA) administered at 1000 ppm in diet to mice for 12 weeks induced a high incidence of lymphocytic leukemia. Effects of NFTA on antibody-mediated immunity and cell-mediated immunity of BALB/c mice were studied using the spleen plaque assay for detection of immunoglobulin M-producing cells and the graft-versus-host (GVH) reaction, respectively. NFTA suppressed both responses. With the spleen plaque assay, the number of antibody-forming cells (AFC) to sheep red blood cells was significantly less than in unmedicated, control mice after treated mice received NFTA at 1000 ppm for 6 days. The GVH reaction was not suppressed at 21 days, but was severely suppressed at 70 days, prior to the histological appearance of leukemia. Effect of dose was studied by administering NFTA at 100, 250, 500, and 1000 ppm of diet for 13 to 14 weeks and then determining the response in the spleen plaque assay and GVH reactions. The ratio of AFC/spleen of NFTA-treated groups to AFC/spleen of an unmedicated control group, at the above specified doses, was 0.86, 0.22, 0.33, and 0.54 in ascending dosage order beginning with 100 ppm. For the GVH reaction, the suppression of the cell-mediated immunity was directly proportional to the dose of NFTA. Suppression of the antibody-mediated immunity in relation to the induction of leukemia at 28 weeks was studied by feeding NFTA at 500 ppm for 14 weeks, followed by unmedicated diet for 14 weeks. During the 11th week, mice were immunized with SRBC; 5 days later the spleens were removed and the spleen plaque assay was performed. Eight of 18 mice fed NFTA developed leukemia. The number of AFC/spleen was 78 X 10(3) +/- 34 for those with leukemia and 68 X 10(3) +/- 24 (p greater than 0.5) for those without leukemia, compared with 170 X 10(3) +/- 74 for the control mice (p less than 0.01 for both groups, compared with controls). A closely related carcinogenic nitrofuran, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, did not suppress the antibody-mediated immunity response measured during the 11th week of administration."}
{"id": "PMID:14784", "title": "Inhibitors of L-asparagine synthetase, in vitro.", "content": "A systematic search has been made for inhibitors of L-asparagine synthetase (L-glutamine hydrolyzing, EC 6.3.5.4) from leukemia 5178Y/AR, a rodent neoplasm resistant to the oncolytic enzyme L-asparaginase (EC 3.5.1.1), The classes of chemicals examined in this search included substrate and product analogs, agents capable of reacting with sulfhydryl functions, and a variety of modifiers whose mechanism of interaction with proteins is known. In general, antagonists of L-glutamine and thiol reagents proved to be the most effective inhibitors of L-asparagine synthetase from this tumor source. Within these groups, certain structural prerequisites to inhibition are reported. Attempts to correlate oncolytic potency with enzyme-inhibitory potency were unsuccesful.", "contents": "Inhibitors of L-asparagine synthetase, in vitro. A systematic search has been made for inhibitors of L-asparagine synthetase (L-glutamine hydrolyzing, EC 6.3.5.4) from leukemia 5178Y/AR, a rodent neoplasm resistant to the oncolytic enzyme L-asparaginase (EC 3.5.1.1), The classes of chemicals examined in this search included substrate and product analogs, agents capable of reacting with sulfhydryl functions, and a variety of modifiers whose mechanism of interaction with proteins is known. In general, antagonists of L-glutamine and thiol reagents proved to be the most effective inhibitors of L-asparagine synthetase from this tumor source. Within these groups, certain structural prerequisites to inhibition are reported. Attempts to correlate oncolytic potency with enzyme-inhibitory potency were unsuccesful."}
{"id": "PMID:14785", "title": "Coprecipitation of active uridine kinase and phosphomonoesterase from rat kidney by Zn2+-ions. III. Enzymes relevant to cancer chemotherapy.", "content": "Partially purified enzyme fraction from rat kidney possessing high uridine kinase and phosphomonoesterase activity was insolubilized by means of zinc precipitation without substantial loss of the activity. While uridine kinase in a soluble and Zn-precipitated form was inhibited by low concentrations (0.5-1.0 mM) of Zn2+-ions, phosphomonoesterase was fully active. In contrast to the soluble fraction, the two enzymes in zinc-precipitated and lyophilized preparations were stable on heating at 100 degrees C. Metal complexed proteins catalyze the dephosphorylation of 5'-UMP, 6-AzaUMP as well as of 2'(3')-UMP or 2,4-dinitrophenyl phosphate indicating thus the presence of several phosphomonoesterases in the complex.", "contents": "Coprecipitation of active uridine kinase and phosphomonoesterase from rat kidney by Zn2+-ions. III. Enzymes relevant to cancer chemotherapy. Partially purified enzyme fraction from rat kidney possessing high uridine kinase and phosphomonoesterase activity was insolubilized by means of zinc precipitation without substantial loss of the activity. While uridine kinase in a soluble and Zn-precipitated form was inhibited by low concentrations (0.5-1.0 mM) of Zn2+-ions, phosphomonoesterase was fully active. In contrast to the soluble fraction, the two enzymes in zinc-precipitated and lyophilized preparations were stable on heating at 100 degrees C. Metal complexed proteins catalyze the dephosphorylation of 5'-UMP, 6-AzaUMP as well as of 2'(3')-UMP or 2,4-dinitrophenyl phosphate indicating thus the presence of several phosphomonoesterases in the complex."}
{"id": "PMID:14790", "title": "Effects of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for alpha- and beta-adrenergic actions.", "content": "We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. Control spontaneous rates for adults and neonates did not differ significantly. There was a biphasic response to all agonists such that rate decreased at low and increased at high concentrations. The decrease was greater with phenylephrine and epinephrine than with isoproterenol. The increase in rate was greater with isoproterenol and epinephrine than with phenylephrine. Propranolol shifted the dose-response curves downward and to the right for all agonists; phentolamine, shifter the curves upward and to the left. Epinephrine and isoproterenol dose-response curves for the neonates were upward and to the left of those for adults. Phenylephrine curves were identical for adults and neonates. Thus there are alpha- and beta-adrenergic effects on Purkinje fiber automaticity; the former decrease and the latter increase rate. Furthermore, the effects on automiticity of beta-adrenergic amines are greater in the neonates than in the adult.", "contents": "Effects of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for alpha- and beta-adrenergic actions. We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. Control spontaneous rates for adults and neonates did not differ significantly. There was a biphasic response to all agonists such that rate decreased at low and increased at high concentrations. The decrease was greater with phenylephrine and epinephrine than with isoproterenol. The increase in rate was greater with isoproterenol and epinephrine than with phenylephrine. Propranolol shifted the dose-response curves downward and to the right for all agonists; phentolamine, shifter the curves upward and to the left. Epinephrine and isoproterenol dose-response curves for the neonates were upward and to the left of those for adults. Phenylephrine curves were identical for adults and neonates. Thus there are alpha- and beta-adrenergic effects on Purkinje fiber automaticity; the former decrease and the latter increase rate. Furthermore, the effects on automiticity of beta-adrenergic amines are greater in the neonates than in the adult."}
{"id": "PMID:14791", "title": "Autonomic control of cardiovascular functions during neonatal development and in adult sheep.", "content": "We studied the autonomic control of resting heart rate of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptor-mediated bradycardia, and acetylcholine-induced systemci hypotension is accompanied by a \"paradoxical\" tachycardia mediated through beta-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists.", "contents": "Autonomic control of cardiovascular functions during neonatal development and in adult sheep. We studied the autonomic control of resting heart rate of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptor-mediated bradycardia, and acetylcholine-induced systemci hypotension is accompanied by a \"paradoxical\" tachycardia mediated through beta-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists."}
{"id": "PMID:14792", "title": "Baroreflex sensitivity in patients with Takayasu's aortitis.", "content": "Takayasu's aortitis is an arterial inflammatory disease of arteries of unknown etiology. Fainting is a common symptom and has been attributed to ypersensitivity of the baroreflex. We studied baroreflex sensitivity in 11 patients with Takayasu's aortitis and compared it with that of eight control subjects of comparable age. Baroreflex sensitivity was assessed by determining the slope of a regression line relating the rise of systolic arterial pressure to the prolongation of the R-R interval of the electrocardiogram during a transient rise of arterial pressure induced by an intravenous injection of phenylephrine. The average baroreflex slope of patients with Takayasu's arteritis (4.0 +/- 0.8 msec/mm Hg) was significantly less than that of control subjects (10.7 +/- 0.8 msec/mm Hg, P less than 0.001). Reduced baroreflex sensitivity in patients with Takayasu's aortitis may be due to the hardening of the arteries where baroreceptors lie, or to hypertension and/or cardiac disease which was present in most of the patients included in this study. Patients with Takayasu's aortitis who complained of fainting also showed the reduced baroreflex sensitivity. This indicates that fainting in this disease is not likely to be caused by the hyperreactivity of the baroreceptors as is commonly postulated.", "contents": "Baroreflex sensitivity in patients with Takayasu's aortitis. Takayasu's aortitis is an arterial inflammatory disease of arteries of unknown etiology. Fainting is a common symptom and has been attributed to ypersensitivity of the baroreflex. We studied baroreflex sensitivity in 11 patients with Takayasu's aortitis and compared it with that of eight control subjects of comparable age. Baroreflex sensitivity was assessed by determining the slope of a regression line relating the rise of systolic arterial pressure to the prolongation of the R-R interval of the electrocardiogram during a transient rise of arterial pressure induced by an intravenous injection of phenylephrine. The average baroreflex slope of patients with Takayasu's arteritis (4.0 +/- 0.8 msec/mm Hg) was significantly less than that of control subjects (10.7 +/- 0.8 msec/mm Hg, P less than 0.001). Reduced baroreflex sensitivity in patients with Takayasu's aortitis may be due to the hardening of the arteries where baroreceptors lie, or to hypertension and/or cardiac disease which was present in most of the patients included in this study. Patients with Takayasu's aortitis who complained of fainting also showed the reduced baroreflex sensitivity. This indicates that fainting in this disease is not likely to be caused by the hyperreactivity of the baroreceptors as is commonly postulated."}
{"id": "PMID:14793", "title": "Amperometric determination of total cholesterol in serum, with use of immobilized cholesterol ester hydrolase and cholesterol oxidase.", "content": "We describe an electrochemical method for simple, rapid, and economical assay of total serum cholesterol with use of immobilized cholesterol esterase (EC 3.1.1.13) and cholesterol oxidase (EC 1.1.3.6). A rotating porous cell was specially designed to hold the immobilized enzymes firmly and to allow the reaction mixture to pass through the enzyme layer easily, thus catalyzing the enzymatic transformation quickly. Hydrogen peroxide resulting from a catalytic reactions was measured amperometrically at +0.60 V cs. a standard calomel electrode. The calibration curve for total serum cholesterol was linear from 0 to 5.00 g/liter. The method is specific, precise, and inexpensive. Our results correlate well with those obtained by the method of Abell et al. [Stand. Methods Clin. Chem. 2, 26 (1958)], the correlation coefficient being 0.992. Ascorbic acid or bilirubin in concentrations up to 700 mg/liter do not interfere. The immobilized enzymes are stable, and the same immobilized-enzyme stirrer can be used for at least 200 accurate, reproducible assays.", "contents": "Amperometric determination of total cholesterol in serum, with use of immobilized cholesterol ester hydrolase and cholesterol oxidase. We describe an electrochemical method for simple, rapid, and economical assay of total serum cholesterol with use of immobilized cholesterol esterase (EC 3.1.1.13) and cholesterol oxidase (EC 1.1.3.6). A rotating porous cell was specially designed to hold the immobilized enzymes firmly and to allow the reaction mixture to pass through the enzyme layer easily, thus catalyzing the enzymatic transformation quickly. Hydrogen peroxide resulting from a catalytic reactions was measured amperometrically at +0.60 V cs. a standard calomel electrode. The calibration curve for total serum cholesterol was linear from 0 to 5.00 g/liter. The method is specific, precise, and inexpensive. Our results correlate well with those obtained by the method of Abell et al. [Stand. Methods Clin. Chem. 2, 26 (1958)], the correlation coefficient being 0.992. Ascorbic acid or bilirubin in concentrations up to 700 mg/liter do not interfere. The immobilized enzymes are stable, and the same immobilized-enzyme stirrer can be used for at least 200 accurate, reproducible assays."}
{"id": "PMID:14794", "title": "Evaluation of a new automatic calcium ion analyzer.", "content": "We evaluated a new automatic analyzer for ionized calcium (Ca2+), the Orion Model SS-20, based on a flowthrough ion-exchange electrode. Ca2+ was measured in heparinized whole blood and serum. Within-day variation was 1.2%, day-to-day variation1.6%, and analytical recovery 92.4%. Over the phsiological range interference by K+ and Mg2+ was negligible; major changes in ionic strength, induced by changes in N+ concentration, made correction for a sodium error necessary. Within the physiological range, Ca2+ was inversely correlated to variations in pH. Therefore, to compare Ca2+ values, correction to an apparent pH of 7.40 should be made. The calcium binding effect of heparin was negligible when minimal (4.4 int. units/ml) concentrations of heparin were used. Storage of serum at 4 degrees C for one week resulted in a 4 degrees decrease in apparent serum Ca2+, primarily owing to an increase in pH during storage. In normal material, mean values for blood-and serum-Ca2+(1.10 and 1.07 mmol/liter, respectively) were close to results obtained by previous systems. Errors caused by disturbances in the fluid flow and non-function of half the electrodes we received were the major inconveniences of the analyzer. We conclude that this new analyzer gives decisive advantages in measurement of Ca2+, making this importnant analysis possible as a routine laboratory test for the first time.", "contents": "Evaluation of a new automatic calcium ion analyzer. We evaluated a new automatic analyzer for ionized calcium (Ca2+), the Orion Model SS-20, based on a flowthrough ion-exchange electrode. Ca2+ was measured in heparinized whole blood and serum. Within-day variation was 1.2%, day-to-day variation1.6%, and analytical recovery 92.4%. Over the phsiological range interference by K+ and Mg2+ was negligible; major changes in ionic strength, induced by changes in N+ concentration, made correction for a sodium error necessary. Within the physiological range, Ca2+ was inversely correlated to variations in pH. Therefore, to compare Ca2+ values, correction to an apparent pH of 7.40 should be made. The calcium binding effect of heparin was negligible when minimal (4.4 int. units/ml) concentrations of heparin were used. Storage of serum at 4 degrees C for one week resulted in a 4 degrees decrease in apparent serum Ca2+, primarily owing to an increase in pH during storage. In normal material, mean values for blood-and serum-Ca2+(1.10 and 1.07 mmol/liter, respectively) were close to results obtained by previous systems. Errors caused by disturbances in the fluid flow and non-function of half the electrodes we received were the major inconveniences of the analyzer. We conclude that this new analyzer gives decisive advantages in measurement of Ca2+, making this importnant analysis possible as a routine laboratory test for the first time."}
{"id": "PMID:14796", "title": "The diagnosis of Gaucher's disease in liver using 4-methylumbelliferyl-beta-D-glucopyranoside.", "content": "1. Cases of Gaucher's disease could not be distinguished from controls by the assay of beta-glucosidase activity in water homogenates of liver using 4-methylumbelliferyl-beta-D glucopyranoside. 2. Two peaks of beta-glucosidase activity were separated by Sephadex G-150 gel filtration in control and Gaucher livers. In the presence of the elution buffer pH profiles of peak I showed a deficiency at pH 3.5-4.5 in Gaucher's disease. Gaucher and control peak II had similar pH profiles with little or no activity at pH 3.0-4.0. 3. A clear distinction between homogenates of Gaucher and control liver was obtained by assay at pH 4.0 in the presence of elution buffer, or of sodium chloride, a component of the elution buffer.", "contents": "The diagnosis of Gaucher's disease in liver using 4-methylumbelliferyl-beta-D-glucopyranoside. 1. Cases of Gaucher's disease could not be distinguished from controls by the assay of beta-glucosidase activity in water homogenates of liver using 4-methylumbelliferyl-beta-D glucopyranoside. 2. Two peaks of beta-glucosidase activity were separated by Sephadex G-150 gel filtration in control and Gaucher livers. In the presence of the elution buffer pH profiles of peak I showed a deficiency at pH 3.5-4.5 in Gaucher's disease. Gaucher and control peak II had similar pH profiles with little or no activity at pH 3.0-4.0. 3. A clear distinction between homogenates of Gaucher and control liver was obtained by assay at pH 4.0 in the presence of elution buffer, or of sodium chloride, a component of the elution buffer."}
{"id": "PMID:14797", "title": "A new semiautomated fluorometric method for estimation of small amounts of L-dopa in human urine.", "content": "A semiautomated fluorometric method for the quantitative determination of urinary dopa, 3-(3,4-dihydroxyphenyl)-L-alanine, is described. It provides a simple, sensitive and reproducible analytical technique for routine use. Dopa is isolated from interfering substances, especially catecholamines, by adsorption onto aluminium oxide, elution with 0.1 M HCl, then passed through a cation-exchange column. By mild oxidation with potassium ferricyanide, dopa is cyclized to dopachrome. This is isomerised with strong alkali to 5,6-substituted indole, which is highly fluorescent but very unstable in the presence of oxygen. The addition of ascorbic acid and 3-mercaptopropionic acid to the alkaline solution stabilizes the fluorescence. Concentrations of chemicals, pH and reaction times are made optimal for maximal sensitivity. Recovery of dopa added to the urine samples averaged 79% (range, 75 to 83). Reproducibility of results from the same urine specimen gave a coefficient of variation of 2.4%. In healthy adults, we found daily excretion ranges from 17.3 to 54.9 (mean: 36.1) microng/24 h or from 0.015 to 0.048 (mean: 0.021) microng/mg cretinine.", "contents": "A new semiautomated fluorometric method for estimation of small amounts of L-dopa in human urine. A semiautomated fluorometric method for the quantitative determination of urinary dopa, 3-(3,4-dihydroxyphenyl)-L-alanine, is described. It provides a simple, sensitive and reproducible analytical technique for routine use. Dopa is isolated from interfering substances, especially catecholamines, by adsorption onto aluminium oxide, elution with 0.1 M HCl, then passed through a cation-exchange column. By mild oxidation with potassium ferricyanide, dopa is cyclized to dopachrome. This is isomerised with strong alkali to 5,6-substituted indole, which is highly fluorescent but very unstable in the presence of oxygen. The addition of ascorbic acid and 3-mercaptopropionic acid to the alkaline solution stabilizes the fluorescence. Concentrations of chemicals, pH and reaction times are made optimal for maximal sensitivity. Recovery of dopa added to the urine samples averaged 79% (range, 75 to 83). Reproducibility of results from the same urine specimen gave a coefficient of variation of 2.4%. In healthy adults, we found daily excretion ranges from 17.3 to 54.9 (mean: 36.1) microng/24 h or from 0.015 to 0.048 (mean: 0.021) microng/mg cretinine."}
{"id": "PMID:14798", "title": "Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain.", "content": "The activities of tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), and monoamine oxidase (MAO) with serotonin and phenylethylamine as substrates were measured in catecholaminergic regions of human brain from 10 controls and 3 patients with Parkinsonism. PNMT activity was detected in hypothalamus, thalamus and cerebellar nucleus of the control human brain, and was reduced in hypothalamus of Parkinsonian cases. Type A (with serotonin as substrate) and type B (with phenylethylamine as substrate) MAO activities were high in all brain regions with little individual variations in controls and Parkinsonian cases. TH activity was high in the controls and was markedly decreased, in substantia nigra, caudate nucleus, putamen and in pallidum, in all three cases of Parkinsonism. DDC activity in these regions was also decreased in 2 patients. However, one Parkinsonian case had only decreased TH and normal DDC activities. DBH activity in hypothalamus was also reduced in the Parkinsonian cases.", "contents": "Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain. The activities of tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), and monoamine oxidase (MAO) with serotonin and phenylethylamine as substrates were measured in catecholaminergic regions of human brain from 10 controls and 3 patients with Parkinsonism. PNMT activity was detected in hypothalamus, thalamus and cerebellar nucleus of the control human brain, and was reduced in hypothalamus of Parkinsonian cases. Type A (with serotonin as substrate) and type B (with phenylethylamine as substrate) MAO activities were high in all brain regions with little individual variations in controls and Parkinsonian cases. TH activity was high in the controls and was markedly decreased, in substantia nigra, caudate nucleus, putamen and in pallidum, in all three cases of Parkinsonism. DDC activity in these regions was also decreased in 2 patients. However, one Parkinsonian case had only decreased TH and normal DDC activities. DBH activity in hypothalamus was also reduced in the Parkinsonian cases."}
{"id": "PMID:14799", "title": "Influence of the pH on the antigen-antibody coupling in angiotensin I radioimmunoassay. Its consequences for the determination of the plasma renin activity.", "content": "The antigen-antibody complex formation in the angiotensin I radioimmunoassay appears to be influenced by the pH of the radioimmunoassay incubation mixture. This may lead to erroneous results in the determination of the plasma renin activity, when an aliquot of a plasma sample, buffered at pH 6 for optimum renin activity is brought into a radioimmunoassay mixture of another pH, while the radioimmunoassay standards are not corrected for this pH shift. In our experiments we studied this general pH effect, and evaluated the effect on the New England Nuclear Angiotensin I radioimmunoassay procedure. We propose a slight modification of this radioimmunoassay kit.", "contents": "Influence of the pH on the antigen-antibody coupling in angiotensin I radioimmunoassay. Its consequences for the determination of the plasma renin activity. The antigen-antibody complex formation in the angiotensin I radioimmunoassay appears to be influenced by the pH of the radioimmunoassay incubation mixture. This may lead to erroneous results in the determination of the plasma renin activity, when an aliquot of a plasma sample, buffered at pH 6 for optimum renin activity is brought into a radioimmunoassay mixture of another pH, while the radioimmunoassay standards are not corrected for this pH shift. In our experiments we studied this general pH effect, and evaluated the effect on the New England Nuclear Angiotensin I radioimmunoassay procedure. We propose a slight modification of this radioimmunoassay kit."}
{"id": "PMID:14802", "title": "Acute overdosage with benzodiazepine derivatives.", "content": "A total of 773 admissions to Massachusetts General Hospital between 1962 and 1975 were due to acute overdosage with one or more psychotropic drugs. Benzodiazepine overdosage, particularly with diazepam, increased relative to other psychotropic drugs over the years. Only 12 admissions were due to benzodiazepine overdosage alone, and none of these patients were seriously ill or had significant complications. Multiple drugs were ingested in the other 87 cases, and the frequency and severity of complications among these individuals depended upon the type and quantity of other nonbenzodiazepines taken. For example, 21 of 31 patients who ingested benzodiazepines together with barbiturates experienced severe central nervous system (CNS) depression, and 14 of 31 required assisted ventilation. However, the frequency of such complications was nearly identical in a group of patients who ingested barbiturates alone. This report and a review of the literature suggest that serious intoxication following overdosage with a benzodiazepine derivative alone is unusual. Ingestion of benzodiazepines together with other drugs appears to be considerably more common than benzodiazepine overdosage alone as a cause of intoxication. The severity of intoxication in such cases of multiple drug ingestion probably depends largely on the type and quantity of nonbenzodiazepines.", "contents": "Acute overdosage with benzodiazepine derivatives. A total of 773 admissions to Massachusetts General Hospital between 1962 and 1975 were due to acute overdosage with one or more psychotropic drugs. Benzodiazepine overdosage, particularly with diazepam, increased relative to other psychotropic drugs over the years. Only 12 admissions were due to benzodiazepine overdosage alone, and none of these patients were seriously ill or had significant complications. Multiple drugs were ingested in the other 87 cases, and the frequency and severity of complications among these individuals depended upon the type and quantity of other nonbenzodiazepines taken. For example, 21 of 31 patients who ingested benzodiazepines together with barbiturates experienced severe central nervous system (CNS) depression, and 14 of 31 required assisted ventilation. However, the frequency of such complications was nearly identical in a group of patients who ingested barbiturates alone. This report and a review of the literature suggest that serious intoxication following overdosage with a benzodiazepine derivative alone is unusual. Ingestion of benzodiazepines together with other drugs appears to be considerably more common than benzodiazepine overdosage alone as a cause of intoxication. The severity of intoxication in such cases of multiple drug ingestion probably depends largely on the type and quantity of nonbenzodiazepines."}
{"id": "PMID:14803", "title": "Effects of metabolic alkalosis, metabolic acidosis and uraemia on whole-body intracellular pH in man.", "content": "1. Whole-body intracellular pH (pHi) was measured by the 14C-labelled DMO method in twenty-four control subjects, eighteen normal subjects with induced acute metabolic alkalosis, ten normal subjects with induced acute metabolic acidosis, twelve normal subjects with chronic acidosis and in fifteen patients with chronic renal insufficiency and acidosis. 2. The change in pHi per unit change in extracellular pH is significantly larger in acute metabolic alkalosis than in acute metabolic acidosis. In chronic metabolic acidosis, pHi decreased in proportion to the total amount of ammonium chloride administered; pHi was normal in patients with uraemic acidosis. 3. These observations confirm the role that tissue buffers play in the protection of the cellular environment in some forms of acidosis. When the acid load overwhelms tissue buffer capacity, pHi becomes a function of extracellular pH. 4. Cells seem more protected from acute acidosis than from acute alkalosis.", "contents": "Effects of metabolic alkalosis, metabolic acidosis and uraemia on whole-body intracellular pH in man. 1. Whole-body intracellular pH (pHi) was measured by the 14C-labelled DMO method in twenty-four control subjects, eighteen normal subjects with induced acute metabolic alkalosis, ten normal subjects with induced acute metabolic acidosis, twelve normal subjects with chronic acidosis and in fifteen patients with chronic renal insufficiency and acidosis. 2. The change in pHi per unit change in extracellular pH is significantly larger in acute metabolic alkalosis than in acute metabolic acidosis. In chronic metabolic acidosis, pHi decreased in proportion to the total amount of ammonium chloride administered; pHi was normal in patients with uraemic acidosis. 3. These observations confirm the role that tissue buffers play in the protection of the cellular environment in some forms of acidosis. When the acid load overwhelms tissue buffer capacity, pHi becomes a function of extracellular pH. 4. Cells seem more protected from acute acidosis than from acute alkalosis."}
{"id": "PMID:14804", "title": "Enzyme activities in human liver biopsies: assay methods and activities of some lysosomal and membrane-bound enzymes in control tissue and serum.", "content": "1. Highly sensitive technique are described for the assay of plasma membrane (5'-nucleotidase, alkaline phosphatase), microsomal (neutral alpha-glucosidase, leucyl-2-naphthylamidase) and biliary canalicular (gamma-glutamyltransferase) enzymes and for nine acid hydrolases (acid phosphatase, phosphodiesterase, beta-glucosidase, alpha-glucosidase, alpha-galactosidase, beta-galactosidase, alpha-mannosidase, N-acetyl-beta-glucosaminidase, beta-glucuronidase) in human liver. 2. Optimum and specific assay systems have been developed which give linear kinetics for all enzymes. 3. The range of enzyme activities in samples of human liver, obtained by closed needle biopsy, and sera have been determined.", "contents": "Enzyme activities in human liver biopsies: assay methods and activities of some lysosomal and membrane-bound enzymes in control tissue and serum. 1. Highly sensitive technique are described for the assay of plasma membrane (5'-nucleotidase, alkaline phosphatase), microsomal (neutral alpha-glucosidase, leucyl-2-naphthylamidase) and biliary canalicular (gamma-glutamyltransferase) enzymes and for nine acid hydrolases (acid phosphatase, phosphodiesterase, beta-glucosidase, alpha-glucosidase, alpha-galactosidase, beta-galactosidase, alpha-mannosidase, N-acetyl-beta-glucosaminidase, beta-glucuronidase) in human liver. 2. Optimum and specific assay systems have been developed which give linear kinetics for all enzymes. 3. The range of enzyme activities in samples of human liver, obtained by closed needle biopsy, and sera have been determined."}
{"id": "PMID:14805", "title": "Lysosomal changes in liver tissue from patients with the Dubin-Johnson-Sprinz syndrome.", "content": "1. Clinical, morphological and biochemical data, including data obtained from the application of subcellular fractionation techniques to liver biopsy specimens, are presented for two patients with the Dubin-Johnson-Sprinz (DJS) syndrome. 2. Subcellular fractionation experiments demonstrate that the lysosomes, which have strikingly reduced equilibrium densities, accumulate melanin. Morphological studies confirm the presence of pigments within lysosomes. 3. Although there are increased activities of lysosomal acid hydrolases in the liver tissue from patients with the DJS syndrome, the integrity of these organelles is essentially normal and therefore the accumulation of pigment would not be expected to initiate liver damage. The DJS syndrome is thus a benign type of secondary lysosomal storage disease.", "contents": "Lysosomal changes in liver tissue from patients with the Dubin-Johnson-Sprinz syndrome. 1. Clinical, morphological and biochemical data, including data obtained from the application of subcellular fractionation techniques to liver biopsy specimens, are presented for two patients with the Dubin-Johnson-Sprinz (DJS) syndrome. 2. Subcellular fractionation experiments demonstrate that the lysosomes, which have strikingly reduced equilibrium densities, accumulate melanin. Morphological studies confirm the presence of pigments within lysosomes. 3. Although there are increased activities of lysosomal acid hydrolases in the liver tissue from patients with the DJS syndrome, the integrity of these organelles is essentially normal and therefore the accumulation of pigment would not be expected to initiate liver damage. The DJS syndrome is thus a benign type of secondary lysosomal storage disease."}
{"id": "PMID:14806", "title": "Leucocyte intracellular pH in patients with the metabolic acidosis of renal failure.", "content": "1. Human leucocytes were isolated from venous blood and resuspended in the subjects plasma. 2. Intracellular pH measurements were made in vitro by the dimethyloxazolidinedione technique in 13 healthy subjects and in 11 subjects with renal failure and metabolic acidosis. 3. The intracellular pH of the healthy subjects was found to be 7-07 (SD 0-04), significantly lower than that of the patients, which was 7-11 (SD 0-03). For all estimations plasma PCO2 was maintained at approximately 5-5 kPa. The methodological and possible metabolic reasons for this difference in intracellular pH are discussed.", "contents": "Leucocyte intracellular pH in patients with the metabolic acidosis of renal failure. 1. Human leucocytes were isolated from venous blood and resuspended in the subjects plasma. 2. Intracellular pH measurements were made in vitro by the dimethyloxazolidinedione technique in 13 healthy subjects and in 11 subjects with renal failure and metabolic acidosis. 3. The intracellular pH of the healthy subjects was found to be 7-07 (SD 0-04), significantly lower than that of the patients, which was 7-11 (SD 0-03). For all estimations plasma PCO2 was maintained at approximately 5-5 kPa. The methodological and possible metabolic reasons for this difference in intracellular pH are discussed."}
{"id": "PMID:14808", "title": "The influence of instructional set on schizophrenic vs. organic concreteness.", "content": "36 male patients (12 schizophrenic, 12 organic, and 12 neurotic), age 19-57, each took two forms of the Gorham Proverbs test under two different instructional sets. It was hypothesized that for schizophrenics, a higher level of abstraction would be obtained on the proverbs task when the instructions required less personal involvement of the patient than when a more personalized set was used; whereas the performance of organic and neurotic patients would not be affected by the variation in instructional set. The results indicate that instructional set does significantly alter the concreteness of the schizophrenic's response to proverbs, but has little effect on the responses of the other two groups.", "contents": "The influence of instructional set on schizophrenic vs. organic concreteness. 36 male patients (12 schizophrenic, 12 organic, and 12 neurotic), age 19-57, each took two forms of the Gorham Proverbs test under two different instructional sets. It was hypothesized that for schizophrenics, a higher level of abstraction would be obtained on the proverbs task when the instructions required less personal involvement of the patient than when a more personalized set was used; whereas the performance of organic and neurotic patients would not be affected by the variation in instructional set. The results indicate that instructional set does significantly alter the concreteness of the schizophrenic's response to proverbs, but has little effect on the responses of the other two groups."}
{"id": "PMID:14812", "title": "Pulmonary artery involvement in Takayasu's arteritis.", "content": "Although pulmonary artery disease in Takayasu's arteritis has been described since 1940, it has received little attention. The clinical, hemodynamic, and angiographic features of the pulmonary involvement were studied in 22 patients with systemic arterial disease. Pulmonary involvement was found in 50 percent of the cases. Moderate pulmonary hypertension was a common finding (73 percent). Lesions were generally localized to the large and medium pulmonary vessels. None of the patients had pulmonary symptoms, but in 63 percent there were clinical, radiologic and electrocardiographic findings suggesting pulmonary hypertension or right heart strain. We believe that the pulmonary circulation should be routinely studied in patients with Takayasu's arteritis and that pulmonary involvement should be included in the classification of the disease.", "contents": "Pulmonary artery involvement in Takayasu's arteritis. Although pulmonary artery disease in Takayasu's arteritis has been described since 1940, it has received little attention. The clinical, hemodynamic, and angiographic features of the pulmonary involvement were studied in 22 patients with systemic arterial disease. Pulmonary involvement was found in 50 percent of the cases. Moderate pulmonary hypertension was a common finding (73 percent). Lesions were generally localized to the large and medium pulmonary vessels. None of the patients had pulmonary symptoms, but in 63 percent there were clinical, radiologic and electrocardiographic findings suggesting pulmonary hypertension or right heart strain. We believe that the pulmonary circulation should be routinely studied in patients with Takayasu's arteritis and that pulmonary involvement should be included in the classification of the disease."}
{"id": "PMID:14813", "title": "Three types of paranoid processes.", "content": "In classical descriptive psychiatry the term 'paranoid' is often used ambiguously -- referring to a variety of clinical processes which should be more clearly differentiated. Specifically, in this paper, we have differentiated three distinct sets of clinical phenomena all usually lumped together as 'paranoid': 1. Paranoid from a Sense of Guilt, 2. Paranoid from a sense of Low Self-Esteem, and 3. Paranoid from a Sense of Persecution. These three processes are distinct descriptively, dynamically and genetically. Further, this differentiation is most significant pragmatically as the treatment is different for each type.", "contents": "Three types of paranoid processes. In classical descriptive psychiatry the term 'paranoid' is often used ambiguously -- referring to a variety of clinical processes which should be more clearly differentiated. Specifically, in this paper, we have differentiated three distinct sets of clinical phenomena all usually lumped together as 'paranoid': 1. Paranoid from a Sense of Guilt, 2. Paranoid from a sense of Low Self-Esteem, and 3. Paranoid from a Sense of Persecution. These three processes are distinct descriptively, dynamically and genetically. Further, this differentiation is most significant pragmatically as the treatment is different for each type."}
{"id": "PMID:14809", "title": "Application of the Starling resistor concept to the lungs during CPPV.", "content": "The application of the Starling resistor concept of the lungs during continuous positive pressure ventilation (CPPV) was evaluated. Ventilation and hemodynamics were studied in eight anesthetized and paralyzed dogs before and during the use of CPPV. CPPV resulted in an increase in transpulmonary pressure and functional residual capacity (FRC), and a decrease in arterial pH and mixed venous oxygen tension (PvO2). Cardica index decreased 32% (p less than 0.01) and stroke volume 51% (p less than 0.01). Neither right nor left transmural pressures changed but pulmonary vascular resistance increased 189% (p less than 0.01). This study supports the concept that the pulmonary vasculature behaves as a Starling resistor during the use of CPPV. The increase in pulmonary vascular resistance must be considered when transpulmonary pressure is raised by CPPV.", "contents": "Application of the Starling resistor concept to the lungs during CPPV. The application of the Starling resistor concept of the lungs during continuous positive pressure ventilation (CPPV) was evaluated. Ventilation and hemodynamics were studied in eight anesthetized and paralyzed dogs before and during the use of CPPV. CPPV resulted in an increase in transpulmonary pressure and functional residual capacity (FRC), and a decrease in arterial pH and mixed venous oxygen tension (PvO2). Cardica index decreased 32% (p less than 0.01) and stroke volume 51% (p less than 0.01). Neither right nor left transmural pressures changed but pulmonary vascular resistance increased 189% (p less than 0.01). This study supports the concept that the pulmonary vasculature behaves as a Starling resistor during the use of CPPV. The increase in pulmonary vascular resistance must be considered when transpulmonary pressure is raised by CPPV."}
{"id": "PMID:14816", "title": "[Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension: the effect of atenolol (author's transl)].", "content": "Plasmin noradrenaline concentration after bicycle exercise (200 W for 2 min), compared with base line concentration, was used as an index of sympathetic responsiveness in patients with essential hypertension. Atenolol (JCI 66082, a \"cardioselective\" beta-blocker) was given in a daily dose of 200 mg to 16 patients for five weeks. This caused a decrease in supine blood pressure of 37/23 and, on standing, of 36/25 mm Hg compared with the placebo period. There was a significant correlation between the ratio of the increase in plasma noradrenaline concentration on exercise over its base line concentration and the subsequent fall in mean arterial pressure (r=0.840; P less than 0.001). There was a less significant correlation between plasma renin concentration and subsequent decrease in mean arterial pressure (r=0.542; P less than 0.05). Administrations of atenolol caused a rise in plasma noradrenaline both on lying and after exercise (P less than 0.0125), and a fall in plasma renin concentration (P less than 0.01). The results suggest that the antihypertensive effect of atenolol is related to the responsiveness of the sympathetic nervous sytem. Adrenergic activity is apparently an important determinant of blood pressure response to beta-blockade.", "contents": "[Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension: the effect of atenolol (author's transl)]. Plasmin noradrenaline concentration after bicycle exercise (200 W for 2 min), compared with base line concentration, was used as an index of sympathetic responsiveness in patients with essential hypertension. Atenolol (JCI 66082, a \"cardioselective\" beta-blocker) was given in a daily dose of 200 mg to 16 patients for five weeks. This caused a decrease in supine blood pressure of 37/23 and, on standing, of 36/25 mm Hg compared with the placebo period. There was a significant correlation between the ratio of the increase in plasma noradrenaline concentration on exercise over its base line concentration and the subsequent fall in mean arterial pressure (r=0.840; P less than 0.001). There was a less significant correlation between plasma renin concentration and subsequent decrease in mean arterial pressure (r=0.542; P less than 0.05). Administrations of atenolol caused a rise in plasma noradrenaline both on lying and after exercise (P less than 0.0125), and a fall in plasma renin concentration (P less than 0.01). The results suggest that the antihypertensive effect of atenolol is related to the responsiveness of the sympathetic nervous sytem. Adrenergic activity is apparently an important determinant of blood pressure response to beta-blockade."}
{"id": "PMID:14818", "title": "[Effect of beta-adrenergic blockers on complement].", "content": "The authors, examined the effect of beta-adrenergic blockers Propranolol, Pindolol, Practonol and P11 on complement in the serum of guinea pigs after continuous administration. The follow-up was made dynamicaly: on the 10th, 20th and 30th day. There was a considerable lowering of the complement level on the 20th and 30th day in all animals treated with beta-adrenergic blockers. The experiments in vitro showed that the effect of Propranolol and and P11 on the serum of persons, guinea pigs and rabbits presented data on the complement inhibition, having the direct effect on the first component of the complementary systems.", "contents": "[Effect of beta-adrenergic blockers on complement]. The authors, examined the effect of beta-adrenergic blockers Propranolol, Pindolol, Practonol and P11 on complement in the serum of guinea pigs after continuous administration. The follow-up was made dynamicaly: on the 10th, 20th and 30th day. There was a considerable lowering of the complement level on the 20th and 30th day in all animals treated with beta-adrenergic blockers. The experiments in vitro showed that the effect of Propranolol and and P11 on the serum of persons, guinea pigs and rabbits presented data on the complement inhibition, having the direct effect on the first component of the complementary systems."}
{"id": "PMID:14819", "title": "[Participation of the adrenals in the pathogenesis of metabolic acid-base disorders].", "content": "The authors examined in dynamics the changes in the functional state of the adrenals on 240 rabbits, which served as models for acute metabolic deviations in the acid-base balance. The obtained results showed that the acute metabolic acidosis increased moderately the values of ACTH and 17-hydroxycorticosteroids in blood without changing their concentration on the adrenal tissue. It lowered strongly the content of catecholamines (adrenaline and noradranaline) in the adrenal medular part. The metabolic alkalosis raised the concentration of ACTH in blood plasma and increased the amount of corticosteroids in blood and adrenals. There was no well formed parallelism in normalizing acid-base and hormonal indices. As a consequence of this a stage of postaciodotic catecholamine adrenal deficit was formed as well as metabasic hypercorticism in the experimental animals.", "contents": "[Participation of the adrenals in the pathogenesis of metabolic acid-base disorders]. The authors examined in dynamics the changes in the functional state of the adrenals on 240 rabbits, which served as models for acute metabolic deviations in the acid-base balance. The obtained results showed that the acute metabolic acidosis increased moderately the values of ACTH and 17-hydroxycorticosteroids in blood without changing their concentration on the adrenal tissue. It lowered strongly the content of catecholamines (adrenaline and noradranaline) in the adrenal medular part. The metabolic alkalosis raised the concentration of ACTH in blood plasma and increased the amount of corticosteroids in blood and adrenals. There was no well formed parallelism in normalizing acid-base and hormonal indices. As a consequence of this a stage of postaciodotic catecholamine adrenal deficit was formed as well as metabasic hypercorticism in the experimental animals."}
{"id": "PMID:14820", "title": "[Comparative study of the effect of haloperidol and maptil on the karyotype and immunoproliferative response of lymphocytes].", "content": "The author examined the action of haloperidol and magetyl on the mitotic activity, blast transformation and karyotype of the lymphocytic cultures, obtained from the peripheral blood in vitro. The experiments were carried out on flymphycytes, obtained from ten healthy individuals. Nontreated cultures, obtained from the same cultures, were used as controls. The following concentrations were used: haloperidol--0.1 mkg/ml, 10 mkg/ml and 10.0 mkg/ml; mageptyl--2.0 mkg/ml, 10,0 mkg/ml and 50 mkg/ml. There was a significant inhibition of the mitotic and blast transformation index after using concentrations of 10.0 mkg/ml both of haloperidol and magentyl. Concentration of 50.0 mkg/ml was toxic for the lymphocytes, obtaine from all donors. Furthermore the two preparations did not induce genomic mutations. Polyploidia, established in the treated cultures, varied slightly from that of the nontreated cultures. There was a weak mutagenic activity of the two preparations at chromosomal level in a concentration of 10.0 mkg/ml.", "contents": "[Comparative study of the effect of haloperidol and maptil on the karyotype and immunoproliferative response of lymphocytes]. The author examined the action of haloperidol and magetyl on the mitotic activity, blast transformation and karyotype of the lymphocytic cultures, obtained from the peripheral blood in vitro. The experiments were carried out on flymphycytes, obtained from ten healthy individuals. Nontreated cultures, obtained from the same cultures, were used as controls. The following concentrations were used: haloperidol--0.1 mkg/ml, 10 mkg/ml and 10.0 mkg/ml; mageptyl--2.0 mkg/ml, 10,0 mkg/ml and 50 mkg/ml. There was a significant inhibition of the mitotic and blast transformation index after using concentrations of 10.0 mkg/ml both of haloperidol and magentyl. Concentration of 50.0 mkg/ml was toxic for the lymphocytes, obtaine from all donors. Furthermore the two preparations did not induce genomic mutations. Polyploidia, established in the treated cultures, varied slightly from that of the nontreated cultures. There was a weak mutagenic activity of the two preparations at chromosomal level in a concentration of 10.0 mkg/ml."}
{"id": "PMID:14821", "title": "Uptake of NADPH by islet secretion granule membranes.", "content": "Reduced nicotinamide adenine dinucleotide phosphate (NADPH), which stimulated the release of insulin from toadfish islet cells and from isolated secretion granules, was taken up by the membranes prepare from these secretion granules. Oxidized nicotinamide adenine dinucleotide phosphate, which did not release insulin from the granules, was taken up to a much lesser extent. The uptake of NADPH by the granule membranes was time dependent, reaching equilibrium in about 30 min. The maximum amount of NADPH taken up was 0.6 nmol/mg membrane protein and the concentration of NADPH needed to obtain maximum uptake was 6.5 x 10(-4)m, which was approximately the same concentration of NADPH needed to produce maximum release of insulin from the secretion granules.", "contents": "Uptake of NADPH by islet secretion granule membranes. Reduced nicotinamide adenine dinucleotide phosphate (NADPH), which stimulated the release of insulin from toadfish islet cells and from isolated secretion granules, was taken up by the membranes prepare from these secretion granules. Oxidized nicotinamide adenine dinucleotide phosphate, which did not release insulin from the granules, was taken up to a much lesser extent. The uptake of NADPH by the granule membranes was time dependent, reaching equilibrium in about 30 min. The maximum amount of NADPH taken up was 0.6 nmol/mg membrane protein and the concentration of NADPH needed to obtain maximum uptake was 6.5 x 10(-4)m, which was approximately the same concentration of NADPH needed to produce maximum release of insulin from the secretion granules."}
{"id": "PMID:14822", "title": "Failure of neurotransmitter blockers to alter PGE2-induced LH release.", "content": "The purpose of this study is to ascertain whether or not prostaglandin (PG) E2 induces LH release by modifying or mudulating the release or action of neural transmitters. PGE2 injected inv into spayed rats primed two days earlier with 10 mug estradiol benzoate increased the plasma levels of LH 10 min later as measured by radio-immunoassay. The peak of plasma LH was not changed by prior treatment with beta- or alpha-adrenergic receptor blockers, propranolol or phenoxybenzamine. The peak level of plasma LH did not alter in rats treated with DL-alpha-methyl-ptyrosine methyl ester HC1 (alpha-MPT) or sodium diethyldithiocarbamate (DDC). Similarly, the peak of plasma LH was not changed by prior treatment with imipramine. Adminisration of PGE2 produced an increase in anterior pituitary and plasma, but not hypothalamic cyclic AMP concomitantly with the elevation in plasma LH. Although it is possible that the effect of PGE2 could be mediated by another transmitter system, as yet unknown, or that the effect of PGE2 on LH release could be mediated via the adenylate cyclase-cyclic AMP system, the results indicate that PGE2 does not act trans-synaptically, but probably acts directly on LH-RH neurons.", "contents": "Failure of neurotransmitter blockers to alter PGE2-induced LH release. The purpose of this study is to ascertain whether or not prostaglandin (PG) E2 induces LH release by modifying or mudulating the release or action of neural transmitters. PGE2 injected inv into spayed rats primed two days earlier with 10 mug estradiol benzoate increased the plasma levels of LH 10 min later as measured by radio-immunoassay. The peak of plasma LH was not changed by prior treatment with beta- or alpha-adrenergic receptor blockers, propranolol or phenoxybenzamine. The peak level of plasma LH did not alter in rats treated with DL-alpha-methyl-ptyrosine methyl ester HC1 (alpha-MPT) or sodium diethyldithiocarbamate (DDC). Similarly, the peak of plasma LH was not changed by prior treatment with imipramine. Adminisration of PGE2 produced an increase in anterior pituitary and plasma, but not hypothalamic cyclic AMP concomitantly with the elevation in plasma LH. Although it is possible that the effect of PGE2 could be mediated by another transmitter system, as yet unknown, or that the effect of PGE2 on LH release could be mediated via the adenylate cyclase-cyclic AMP system, the results indicate that PGE2 does not act trans-synaptically, but probably acts directly on LH-RH neurons."}
{"id": "PMID:14825", "title": "Purification of an endonuclease from adenovirus-infected KB cells.", "content": "This report describes the purification of an endonuclease from extracts of adenovirus-type-2-infected KB cells. Endonuclease activity can also be detected in extracts of uninfected KB cells and the enzyme activities from extracts of uninfected and adenovirus-infected cells are very similar, if not identical. The enzyme has its maximal activity at pH 4.0. The enzyme found in uninfected and adenovirus-infectedcells is, however, strikingly different from an endonuclease isolated from calf serum. Hence, the endonuclease described is probably not a contaminant derived from the medium in which the KB cells were propagated. The endonuclease in crude extracts from uninfected or adenovirus-infected KB cells can be activated or its activity enhanced by treatment of the extracts with proteolytic enzymes, like pronase or trypsin. Evidence has been presented suggesting that this activation is due to proteolytic cleavage of an inhibitor present in crude extracts of uninfected and adenovirus-type-2-infected KB cells. A second endonuclease has been found in extracts of infected and uninfected cells with optimal activity at pH 7.2 and this endonuclease can be separated from the one with a pH optimum at 4.0.", "contents": "Purification of an endonuclease from adenovirus-infected KB cells. This report describes the purification of an endonuclease from extracts of adenovirus-type-2-infected KB cells. Endonuclease activity can also be detected in extracts of uninfected KB cells and the enzyme activities from extracts of uninfected and adenovirus-infected cells are very similar, if not identical. The enzyme has its maximal activity at pH 4.0. The enzyme found in uninfected and adenovirus-infectedcells is, however, strikingly different from an endonuclease isolated from calf serum. Hence, the endonuclease described is probably not a contaminant derived from the medium in which the KB cells were propagated. The endonuclease in crude extracts from uninfected or adenovirus-infected KB cells can be activated or its activity enhanced by treatment of the extracts with proteolytic enzymes, like pronase or trypsin. Evidence has been presented suggesting that this activation is due to proteolytic cleavage of an inhibitor present in crude extracts of uninfected and adenovirus-type-2-infected KB cells. A second endonuclease has been found in extracts of infected and uninfected cells with optimal activity at pH 7.2 and this endonuclease can be separated from the one with a pH optimum at 4.0."}
{"id": "PMID:14826", "title": "Characterization of the pH 4.0 endonuclease from adenovirus-type-2-infected KB cells.", "content": "The properties of the pH 4.0 endonuclease from adenovirus-type-2-infected KB cells were determined. The enzyme has a molecular weight of approximately 40000. Its pH optimum is at pH 4.0, it is not inhibited by ethylenediaminetetraacetate (EDTA), and it is active at temperatures up to 60 degree C. The enzyme cleaves adenovirus DNA in a stepwise manner. The limit digestion product has a molecular weight of 120000-200000. There is evidence that the cleavage reaction proceeds via an initial single-strand nick. Under the conditions tested the endonuclease did not seem to reveal a high degree of specificity as to the recognition of cleavage sites, or else the sites recognized occurred very frequently.", "contents": "Characterization of the pH 4.0 endonuclease from adenovirus-type-2-infected KB cells. The properties of the pH 4.0 endonuclease from adenovirus-type-2-infected KB cells were determined. The enzyme has a molecular weight of approximately 40000. Its pH optimum is at pH 4.0, it is not inhibited by ethylenediaminetetraacetate (EDTA), and it is active at temperatures up to 60 degree C. The enzyme cleaves adenovirus DNA in a stepwise manner. The limit digestion product has a molecular weight of 120000-200000. There is evidence that the cleavage reaction proceeds via an initial single-strand nick. Under the conditions tested the endonuclease did not seem to reveal a high degree of specificity as to the recognition of cleavage sites, or else the sites recognized occurred very frequently."}
{"id": "PMID:14827", "title": "Affinity labeling of rat-kidney gamma-glutamyl transpeptidase.", "content": "The reaction of gamma-glutamyl transpeptidase from rat kidney with a glutamine analog, 6-diazo-5-oxo-L-norleucine, resulted in irreversible inactivation of the enzyme. The concentration of this reagent giving a half-maximum rate of inactivation was 6 mMat pH 7.5. The inactivation was prevented by the presence of reduced glutathione in a competitive fashion, which indicates the active-site-directed nature of this reagent. The rate of inactivation was greatly accelerated in the presence of maleate, which is known to enhance the glutaminase activity of this enzyme. The presence of maleate increased the maximum velocity of the inactivation, but did not affect the affinity of the enzyme for 6-diazo-5-oxo-L-norleucine. Inactivation of the enzyme with 6-diazo-5-oxo-L-[6=14C]norleucine as well as with 6-diazo-5-oxo-L[1,2,3,4,5-14C]norleucine resulted in a stoichiometric incorporation of radioactivity into the enzyme protein via covalent linkage. The amount of radioactivity incorporated was 1 mol 14C label/248000 g enzyme protein. A native enzyme preparation showing a single protein band on polyacrylamide gel electrophoresis gave four distinct bands upon sodium dodecylsulfate/polyacrylamide gel electrophoresis. Upon sodium dodecylsulfate/polyacrylamide gel electrophoresis of the 14C-labeled enzyme, only the band moving the fastest towards the anode was found to contain radioactivity. This finding indicates that this protein band represents the catalytic component of the enzyme.", "contents": "Affinity labeling of rat-kidney gamma-glutamyl transpeptidase. The reaction of gamma-glutamyl transpeptidase from rat kidney with a glutamine analog, 6-diazo-5-oxo-L-norleucine, resulted in irreversible inactivation of the enzyme. The concentration of this reagent giving a half-maximum rate of inactivation was 6 mMat pH 7.5. The inactivation was prevented by the presence of reduced glutathione in a competitive fashion, which indicates the active-site-directed nature of this reagent. The rate of inactivation was greatly accelerated in the presence of maleate, which is known to enhance the glutaminase activity of this enzyme. The presence of maleate increased the maximum velocity of the inactivation, but did not affect the affinity of the enzyme for 6-diazo-5-oxo-L-norleucine. Inactivation of the enzyme with 6-diazo-5-oxo-L-[6=14C]norleucine as well as with 6-diazo-5-oxo-L[1,2,3,4,5-14C]norleucine resulted in a stoichiometric incorporation of radioactivity into the enzyme protein via covalent linkage. The amount of radioactivity incorporated was 1 mol 14C label/248000 g enzyme protein. A native enzyme preparation showing a single protein band on polyacrylamide gel electrophoresis gave four distinct bands upon sodium dodecylsulfate/polyacrylamide gel electrophoresis. Upon sodium dodecylsulfate/polyacrylamide gel electrophoresis of the 14C-labeled enzyme, only the band moving the fastest towards the anode was found to contain radioactivity. This finding indicates that this protein band represents the catalytic component of the enzyme."}
{"id": "PMID:14828", "title": "Superoxide dismutase from Thermus aquaticus. Isolation and characterisation of manganese and apo enzymes.", "content": "Superoxide dismutase has been isolated and characterised from the extreme thermophile Thermus aquaticus. The pure enzyme is a reddish-purple manganese-containing protein with a molecular weight of approximately 80000 +/- 5000. Combination of gel electrophoresis in dodecylsulphate and amino acid analysis shows that it is composed of four identical subunit polypeptide chains consisting of approximately 186 amino acids. The tetrameric protein contains two atoms of manganese. A stable manganese-free apoprotein has been prepared by treatment with EDTA in 8 M urea at acidic pH. The apoprotein regains the tetrameric structure in the absence of manganese but is inactive. Reconstitution of active Mn-enzyme was achieved byaddition of Mm2+ apoprotein in 8 M urea at acid pH. Reconstitution was monitored by absorption spectroscopy, manganese analysis and regain of activity and by these criteria the reconstituted enyzme with two atoms Mn per mole is indistinguishable from the native enzyme. The enhanced stability of the thermophile apoenzyme and Mn-enzyme is of advantage for studies of the structure and mechanism of action of superoxide dismutase. The N-terminal amino acid sequence to the 40th residue of the submit was determined by automated Edman degradation. The sequence has a close resemblance to that of the dimeric Mn-enzyme from another thermophile, Bacillus stearothermophilus.", "contents": "Superoxide dismutase from Thermus aquaticus. Isolation and characterisation of manganese and apo enzymes. Superoxide dismutase has been isolated and characterised from the extreme thermophile Thermus aquaticus. The pure enzyme is a reddish-purple manganese-containing protein with a molecular weight of approximately 80000 +/- 5000. Combination of gel electrophoresis in dodecylsulphate and amino acid analysis shows that it is composed of four identical subunit polypeptide chains consisting of approximately 186 amino acids. The tetrameric protein contains two atoms of manganese. A stable manganese-free apoprotein has been prepared by treatment with EDTA in 8 M urea at acidic pH. The apoprotein regains the tetrameric structure in the absence of manganese but is inactive. Reconstitution of active Mn-enzyme was achieved byaddition of Mm2+ apoprotein in 8 M urea at acid pH. Reconstitution was monitored by absorption spectroscopy, manganese analysis and regain of activity and by these criteria the reconstituted enyzme with two atoms Mn per mole is indistinguishable from the native enzyme. The enhanced stability of the thermophile apoenzyme and Mn-enzyme is of advantage for studies of the structure and mechanism of action of superoxide dismutase. The N-terminal amino acid sequence to the 40th residue of the submit was determined by automated Edman degradation. The sequence has a close resemblance to that of the dimeric Mn-enzyme from another thermophile, Bacillus stearothermophilus."}
{"id": "PMID:14829", "title": "PH-dependent changes of 2,3-bisphosphoglycerate in human red cells during transitional and steady states in vitro.", "content": "A systematic study of the pH-dependent changes in the range 6.6--7.4 of 2,3-bisphosphoglycerate and the adenine nucleotides was performed in the presence and absence of glucose during transitional and steady states. 1. The results indicatethat 2,3-gisphosphoglycerate phosphatase breaks down 2,3-bisphosphoglycerate nearly independent of pH at a rate of 480 mumol 2,3-bisphosphoglycerate x1 cells-1xh-1.2,3-Bisphosphoglycerate mutase is practically completely inhibited below pH value increases in long-term experiments with lower 2,3-bisphosphoglycerate levels. The formation of pyruvate corresponds to the breakdown of 2,3-bisphosphoglycerate afterconsumption of an unknown reducing substance.", "contents": "PH-dependent changes of 2,3-bisphosphoglycerate in human red cells during transitional and steady states in vitro. A systematic study of the pH-dependent changes in the range 6.6--7.4 of 2,3-bisphosphoglycerate and the adenine nucleotides was performed in the presence and absence of glucose during transitional and steady states. 1. The results indicatethat 2,3-gisphosphoglycerate phosphatase breaks down 2,3-bisphosphoglycerate nearly independent of pH at a rate of 480 mumol 2,3-bisphosphoglycerate x1 cells-1xh-1.2,3-Bisphosphoglycerate mutase is practically completely inhibited below pH value increases in long-term experiments with lower 2,3-bisphosphoglycerate levels. The formation of pyruvate corresponds to the breakdown of 2,3-bisphosphoglycerate afterconsumption of an unknown reducing substance."}
{"id": "PMID:14830", "title": "Carboxyl groups at the two active centers of sucrase-isomaltase from rabbit small intestine.", "content": "1. Seveal selective reagents were employed to identify the amino acid residues essential for the catalytic activity of sucrase-isomaltase. 2. Modification of histidine, lysine and carboxyl residues resulted in a partial inactivation of the enzyme. Substrates or competitive inhibitors provided protection against inactivation only in the reaction of carboxyl groups with carbodiimide (+lycine ethyl ester) or with diazoacetic ethyl ester. This indicated the occurrence of carboxyl groups at the two active centers of the enzyme complex. 3. Protection against inactivation of the enzyme by carbodiimide was provided also by the presence of alkali and alkaline earth metal ions, which are non-essential activators of sucrase-isomaltase. The presence of Na+ and Ba2+ protected approximately one carboxyl group per active center from reacting with carbodiimide plus glycine ethyl ester. 4. The carbodiimide-reactive groups were not identical with the two carboxylate groups recently found to react with conduritol-B-epoxide, an active-site-directed inhibitor of sucrase-isomaltase (Quaroni, A. and Semenza, G., 1976, J. Biol. Chem 251,3250--3253). A possible role for the carbodiimide-reactive carboxyl groups at the active centers of sucrase-isomaltase is discussed.", "contents": "Carboxyl groups at the two active centers of sucrase-isomaltase from rabbit small intestine. 1. Seveal selective reagents were employed to identify the amino acid residues essential for the catalytic activity of sucrase-isomaltase. 2. Modification of histidine, lysine and carboxyl residues resulted in a partial inactivation of the enzyme. Substrates or competitive inhibitors provided protection against inactivation only in the reaction of carboxyl groups with carbodiimide (+lycine ethyl ester) or with diazoacetic ethyl ester. This indicated the occurrence of carboxyl groups at the two active centers of the enzyme complex. 3. Protection against inactivation of the enzyme by carbodiimide was provided also by the presence of alkali and alkaline earth metal ions, which are non-essential activators of sucrase-isomaltase. The presence of Na+ and Ba2+ protected approximately one carboxyl group per active center from reacting with carbodiimide plus glycine ethyl ester. 4. The carbodiimide-reactive groups were not identical with the two carboxylate groups recently found to react with conduritol-B-epoxide, an active-site-directed inhibitor of sucrase-isomaltase (Quaroni, A. and Semenza, G., 1976, J. Biol. Chem 251,3250--3253). A possible role for the carbodiimide-reactive carboxyl groups at the active centers of sucrase-isomaltase is discussed."}
{"id": "PMID:14831", "title": "A mutant ATP synthetase of Escherichia coli with an altered sensitivity to N,N' -dicyclohexylcarbodiimide: characterization in native membranes and reconstituted proteoliposomes.", "content": "Dicyclohexylcarbodiimide-resistant mutants of Escherichia coli were isolated and characterized In one mutant the unc genes and affects the membrane-integrated part of the ATP synthetase. The sensitivity of ATP synthetase functions to N,N' -dicyclohexylcarbodiimide was compared in wild-type and mutant membranes. The membrane-integrated part of the wild-type ATP synthetase is highly sensitive to ATP-dependent membrane energization and restoration of lactate-dependent energization of ATPase-depleted membranes. In mutant membranes this concentration has only a slight effect on these activities whereas a severe inhibition is obtained at 200 muM. Using  the highly water-soluble 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide theactivities of wild-type and mutant membranes are inhibited to the same extent. TheATP synthetase of wild-type and mutant was partially purified and incorporated muM. Uinto liposomes. These showed an uncoupler-sensitive ATP-32Pi exchange and ATP-dependent quenching of acridine-dye fluorescence. The activities of mutant and wild-type proteoliposomes exhibit the same pattern of sensitivity to dicyclohexylcarbodiimide as the corresponding membranes.", "contents": "A mutant ATP synthetase of Escherichia coli with an altered sensitivity to N,N' -dicyclohexylcarbodiimide: characterization in native membranes and reconstituted proteoliposomes. Dicyclohexylcarbodiimide-resistant mutants of Escherichia coli were isolated and characterized In one mutant the unc genes and affects the membrane-integrated part of the ATP synthetase. The sensitivity of ATP synthetase functions to N,N' -dicyclohexylcarbodiimide was compared in wild-type and mutant membranes. The membrane-integrated part of the wild-type ATP synthetase is highly sensitive to ATP-dependent membrane energization and restoration of lactate-dependent energization of ATPase-depleted membranes. In mutant membranes this concentration has only a slight effect on these activities whereas a severe inhibition is obtained at 200 muM. Using  the highly water-soluble 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide theactivities of wild-type and mutant membranes are inhibited to the same extent. TheATP synthetase of wild-type and mutant was partially purified and incorporated muM. Uinto liposomes. These showed an uncoupler-sensitive ATP-32Pi exchange and ATP-dependent quenching of acridine-dye fluorescence. The activities of mutant and wild-type proteoliposomes exhibit the same pattern of sensitivity to dicyclohexylcarbodiimide as the corresponding membranes."}
{"id": "PMID:14832", "title": "Proton movements coupled to sugar transport via the galactose transport system in Salmonella typhimurium.", "content": "We have studied proton movements associated with substrate transport via the galactose transport system in Salmonella typhimurium. The addition of galactose to lightly buffered suspensions of anaerobic, non-metabolizing cells of Salmonella typhimurium, specifically induced for the galactose transport system, causes an increase in extracellularpH as galactose and protons enter the cell together. Other substrates for this transport system, D-fucose, 2-deoxygalactose, glucose and 2-deoxyglucose similarly cause an influx of protons when transported. In contrast, transport via the other major transport system for galactose, the methylgalactoside transport system, is not coupled to H+ influx. Comparison of kinetic data obtained from pH measurements with data obtained from measurement of active transport of galactose via the galactose transport system suggests that the apparent Km of the galactose transport system for this sugar differs under energized and non-energized conditions. At pH 7.2 the permeant anion SCN- increases both the rate and extent of galactose-induced proton influx; at pH 6 the rate, but not the extent is increased by SCN-.", "contents": "Proton movements coupled to sugar transport via the galactose transport system in Salmonella typhimurium. We have studied proton movements associated with substrate transport via the galactose transport system in Salmonella typhimurium. The addition of galactose to lightly buffered suspensions of anaerobic, non-metabolizing cells of Salmonella typhimurium, specifically induced for the galactose transport system, causes an increase in extracellularpH as galactose and protons enter the cell together. Other substrates for this transport system, D-fucose, 2-deoxygalactose, glucose and 2-deoxyglucose similarly cause an influx of protons when transported. In contrast, transport via the other major transport system for galactose, the methylgalactoside transport system, is not coupled to H+ influx. Comparison of kinetic data obtained from pH measurements with data obtained from measurement of active transport of galactose via the galactose transport system suggests that the apparent Km of the galactose transport system for this sugar differs under energized and non-energized conditions. At pH 7.2 the permeant anion SCN- increases both the rate and extent of galactose-induced proton influx; at pH 6 the rate, but not the extent is increased by SCN-."}
{"id": "PMID:14833", "title": "Intramolecularly-quenched fluorescent peptides as fluorogenic substrates ofleucine aminopeptidase and inhibitors of clostridial aminopeptidase.", "content": "Fluorogenic oligopeptide derivatives of the type Lys(ABz)-ONBzl, where ABz iso-aminobenzoyl (anthraniloyl), X stands for Ala Phe, or Ala-Ala, and ONBzlis p-nitrobenzyloxy, were synthesized and shown to be hydrolyzed by leucine aminopeptidase. The hydrolysis is accompanied by an increase in fluorescence due to disruptionof the intramolecular quenching of the fluorescent anthraniloyl moiety by the nitrobenzyester group. The spectral characteristics of the compounds are not consistent withan energy transfer mechanism according to F\u00f6rster, therefore the quenching isassumed to be caused by a direct encouter between the quenching and the fluorecentgroups. The change in fluorescence that accompanies the enzymic hydrolysis ofthe first peptide bound was used for quantitative measurement of the activity ofthe activity of leucine aminopeptidase and for the determination of some of itskinetic parameters. A bacterial aminopeptidase from Clostrdium histolyticumthat is very similar to leucine aminopeptidase in its substrate specificity inits substrate specificity did not hydrolyze the above peptidederivatives. Thehydrolysis of leucine p-nitroanilide by this enzyme was found to be inhibitedby the three peptides and the corresponding inhibition constants were determined.", "contents": "Intramolecularly-quenched fluorescent peptides as fluorogenic substrates ofleucine aminopeptidase and inhibitors of clostridial aminopeptidase. Fluorogenic oligopeptide derivatives of the type Lys(ABz)-ONBzl, where ABz iso-aminobenzoyl (anthraniloyl), X stands for Ala Phe, or Ala-Ala, and ONBzlis p-nitrobenzyloxy, were synthesized and shown to be hydrolyzed by leucine aminopeptidase. The hydrolysis is accompanied by an increase in fluorescence due to disruptionof the intramolecular quenching of the fluorescent anthraniloyl moiety by the nitrobenzyester group. The spectral characteristics of the compounds are not consistent withan energy transfer mechanism according to F\u00f6rster, therefore the quenching isassumed to be caused by a direct encouter between the quenching and the fluorecentgroups. The change in fluorescence that accompanies the enzymic hydrolysis ofthe first peptide bound was used for quantitative measurement of the activity ofthe activity of leucine aminopeptidase and for the determination of some of itskinetic parameters. A bacterial aminopeptidase from Clostrdium histolyticumthat is very similar to leucine aminopeptidase in its substrate specificity inits substrate specificity did not hydrolyze the above peptidederivatives. Thehydrolysis of leucine p-nitroanilide by this enzyme was found to be inhibitedby the three peptides and the corresponding inhibition constants were determined."}
{"id": "PMID:14834", "title": "Hypoxanthine levels of plasma during hypoxemia in dogs.", "content": "Tissue hypoxia was induced in one group of dogs by clamping of the endotracheal tube and in another group by artificial ventilation with a mixture of nitrogen and air. The hypoxanthine concentration of venous and arterial plasma increased significantly during severe hypoxemia. When the hypoxemia was relieved, an increased venous-arterial hypoxanthine difference appeared indicating that the lung metabolism of hypoxanthine was slowed down during alveolar hypoxia. It is concluded that the level of plasma hypoxanthine in dogs during hypoxemia is dependent on the degree of tissue hypoxia, peripheral vasoregulation, and lung metabolism.", "contents": "Hypoxanthine levels of plasma during hypoxemia in dogs. Tissue hypoxia was induced in one group of dogs by clamping of the endotracheal tube and in another group by artificial ventilation with a mixture of nitrogen and air. The hypoxanthine concentration of venous and arterial plasma increased significantly during severe hypoxemia. When the hypoxemia was relieved, an increased venous-arterial hypoxanthine difference appeared indicating that the lung metabolism of hypoxanthine was slowed down during alveolar hypoxia. It is concluded that the level of plasma hypoxanthine in dogs during hypoxemia is dependent on the degree of tissue hypoxia, peripheral vasoregulation, and lung metabolism."}
{"id": "PMID:14835", "title": "Protective action of timolol in acute myocardial ischemia.", "content": "Timolol, a beta-adrenoceptor blocking agent with little or no cardiodepressant activity, was studied in acute myocardial ischemia in cats. Timolol, at a dose of 25 mug/kg, blocked 75 to 80% of the cardiac response to isoproterenol. This dose also significantly reduced heart rate in cats subjected to acute myocardial ischemia by ligation of the left coronary artery. Timolol significantly prevented the spread of ischemic damage in the myocardium as assessed by (a) curtailing the increase in plasma creatine phosphokinase (CPK) activity, (b) preventing the loss of CPK from the ischemic portion of the myocardium, and (c) restoring the elevated S-T segment of the electrocardiogram toward normal. Timolol did not significantly retard the increase in fragility of lysosomes in ischemic myocardial tissue. The mechanism of the protective effect to timolol on the ischemic myocardium appears to be via reducing myocardial oxygen demand by decreasing heart rate.", "contents": "Protective action of timolol in acute myocardial ischemia. Timolol, a beta-adrenoceptor blocking agent with little or no cardiodepressant activity, was studied in acute myocardial ischemia in cats. Timolol, at a dose of 25 mug/kg, blocked 75 to 80% of the cardiac response to isoproterenol. This dose also significantly reduced heart rate in cats subjected to acute myocardial ischemia by ligation of the left coronary artery. Timolol significantly prevented the spread of ischemic damage in the myocardium as assessed by (a) curtailing the increase in plasma creatine phosphokinase (CPK) activity, (b) preventing the loss of CPK from the ischemic portion of the myocardium, and (c) restoring the elevated S-T segment of the electrocardiogram toward normal. Timolol did not significantly retard the increase in fragility of lysosomes in ischemic myocardial tissue. The mechanism of the protective effect to timolol on the ischemic myocardium appears to be via reducing myocardial oxygen demand by decreasing heart rate."}
{"id": "PMID:14836", "title": "Studies on the antagonism by raphe lesions of the antinociceptive action of systemic morphine.", "content": "In rats, lesions were placed in the dorsal/median raphe (DMR), in the ventral raphe (VR: raphe magnus), in both the dorsal/median and ventral raphe (DMVR) or in the reticular formation (RF). The effect of the lesions on the antinociception and catalepsy produced by 3 doses of morphine (3, 10 and 30 mg/kg) was examined. The lesions had no significant effect on the catalepsy produced by any of the doses of morphine tested. DMR lesions produced a partial attentuation of the antinociceptive action of both the 3 and 10 mg doses. VR lesions produced a complete blockade of the 3 mg and only a partial attenuation of the 10 mg dose. In contrast, the combined (DMVR) lesions yielded virtually a total blockade of the 3 and 10 mg. Yet, as with the DMR and VR groups, the DMVR lesions failed to produce a significant antagonism on either of the nociceptive tests at the 30 mg dose. These findings suggest that the ascending and descending fiber systems emanating from the dorsal/median and ventral raphe, respectively, facilitate the expression of morphine-induced analgesia but that neither system alone can be regarded as essential for the manifestation of the antinociceptive effects of systematically administered morphine.", "contents": "Studies on the antagonism by raphe lesions of the antinociceptive action of systemic morphine. In rats, lesions were placed in the dorsal/median raphe (DMR), in the ventral raphe (VR: raphe magnus), in both the dorsal/median and ventral raphe (DMVR) or in the reticular formation (RF). The effect of the lesions on the antinociception and catalepsy produced by 3 doses of morphine (3, 10 and 30 mg/kg) was examined. The lesions had no significant effect on the catalepsy produced by any of the doses of morphine tested. DMR lesions produced a partial attentuation of the antinociceptive action of both the 3 and 10 mg doses. VR lesions produced a complete blockade of the 3 mg and only a partial attenuation of the 10 mg dose. In contrast, the combined (DMVR) lesions yielded virtually a total blockade of the 3 and 10 mg. Yet, as with the DMR and VR groups, the DMVR lesions failed to produce a significant antagonism on either of the nociceptive tests at the 30 mg dose. These findings suggest that the ascending and descending fiber systems emanating from the dorsal/median and ventral raphe, respectively, facilitate the expression of morphine-induced analgesia but that neither system alone can be regarded as essential for the manifestation of the antinociceptive effects of systematically administered morphine."}
{"id": "PMID:14837", "title": "Attenuation of morphine analgesia in rats with lesions of the locus coeruleus and dorsal raphe nucleus.", "content": "The nociceptive reflex activity and analgesic effect of morphine were studied in rats using the hind paw stimulation test. The stimulation threshold was significantly increased in animals with bilateral destruction of the locus coeruleus (LC), and was reduced after lesion of the dorsal raphe nucleus (DR). LC lesions produced a selective lowering of noradrenaline (NA) content in the forebrain, while DR lesions resulted in a reduction in serotonin levels. Lesioning both LC and DR significantly reduced both NA and serotonin contents even when the stimulation threshold was not altered. Morphine produced a significant and dose-dependent elevation of the stimulation threshold in sham-operated animals, while morphine analgesia was almost completely inhibited by destruction of LC, DR and both the nuclei. These results imply that a depression of LC-mediated noradrenergic tone results in a decreased sensitivity to painful stimuli, whereas a reduction of raphe-derived serotonergic tone produces the opposite effect against LC. It is suggested, however, that both of these monoamines from the LC and DR are necessary for the analgesic effect of morphine.", "contents": "Attenuation of morphine analgesia in rats with lesions of the locus coeruleus and dorsal raphe nucleus. The nociceptive reflex activity and analgesic effect of morphine were studied in rats using the hind paw stimulation test. The stimulation threshold was significantly increased in animals with bilateral destruction of the locus coeruleus (LC), and was reduced after lesion of the dorsal raphe nucleus (DR). LC lesions produced a selective lowering of noradrenaline (NA) content in the forebrain, while DR lesions resulted in a reduction in serotonin levels. Lesioning both LC and DR significantly reduced both NA and serotonin contents even when the stimulation threshold was not altered. Morphine produced a significant and dose-dependent elevation of the stimulation threshold in sham-operated animals, while morphine analgesia was almost completely inhibited by destruction of LC, DR and both the nuclei. These results imply that a depression of LC-mediated noradrenergic tone results in a decreased sensitivity to painful stimuli, whereas a reduction of raphe-derived serotonergic tone produces the opposite effect against LC. It is suggested, however, that both of these monoamines from the LC and DR are necessary for the analgesic effect of morphine."}
{"id": "PMID:14838", "title": "Pharmacological characterisation of the presynaptic alpha-adrenoceptor in the rat vas deferens.", "content": "The interactions between alpha-adrenoceptor agonists and antagonists on the twitch response of the rat isolated vas deferens to low frequency motor nerve stimulatioh have been examined. Oxymetazoline, clonidine, naphazoline and BAY-1470 caused a concentration-dependent inhibition of the twitch response at concentrations lower than those causing smooth muscle stimulation. The twitch-inhibitory effect of these compounds is thought to result from stimulation of presynaptically located alpha-adrenoceptors. In contrast, phenylephrine and methoxamine exerted little inhibitory effect at concentrations less than those which produced postsynaptic stimulation. The inhibitory effect of clonidine was antagonised by phentolamine, piperoxan, yohimbine and tolazoline, but not by thymoxamine. These results characterise the presynaptic alpha-adrenoceptors in the rat vas deferens as being of the same type as those present in the rabbit pulmonary artery and rat heart, but different from those located post-synaptically in sympathetically innervated tissues.", "contents": "Pharmacological characterisation of the presynaptic alpha-adrenoceptor in the rat vas deferens. The interactions between alpha-adrenoceptor agonists and antagonists on the twitch response of the rat isolated vas deferens to low frequency motor nerve stimulatioh have been examined. Oxymetazoline, clonidine, naphazoline and BAY-1470 caused a concentration-dependent inhibition of the twitch response at concentrations lower than those causing smooth muscle stimulation. The twitch-inhibitory effect of these compounds is thought to result from stimulation of presynaptically located alpha-adrenoceptors. In contrast, phenylephrine and methoxamine exerted little inhibitory effect at concentrations less than those which produced postsynaptic stimulation. The inhibitory effect of clonidine was antagonised by phentolamine, piperoxan, yohimbine and tolazoline, but not by thymoxamine. These results characterise the presynaptic alpha-adrenoceptors in the rat vas deferens as being of the same type as those present in the rabbit pulmonary artery and rat heart, but different from those located post-synaptically in sympathetically innervated tissues."}
{"id": "PMID:14839", "title": "The effect of guanethidine and hydrochlorothiazide on blood pressure and vascular tyrosine hydroxylase activity in the spontaneously hypertensive rat.", "content": "The present study examined the effects of antihypertensive drugs (hydrochlorothiazide and guanethidine) on blood pressure and tyrosine hydroxylase (TH) activity in the spontaneously hypertensive rat (SHR). Hydrochlorothiazide (50 mg/kg X 4 days) lowered blood pressure in the SHR to a degree equivalent to that produced by reserpine (0.3 mg/kg X 3 days). However, while reserpine increased vascular and adrenal TH activity, hydrochlorothiazide had no effect. Guanethidine (30 mg/kg X 2 days) reduced blood pressure in the SHR and also depleted cardiac, vascular and adrenal gland catecholamines; However, guanethidine administration did not increase TH activity in the mesenteric vasculature or adrenal glands. These studies indicate that at equieffective blood pressure lowering doses, different antihypertensive drugs have different effects on TH activity in the SHR. Neither blood pressure reduction nor catecholamine depletion in peripheral tissues are sufficient prerequisties for increasing TH activity. The data support the suggestion, however, that amine depletion in the central nervous system or ganglia may be an important factor in the regulation of TH.", "contents": "The effect of guanethidine and hydrochlorothiazide on blood pressure and vascular tyrosine hydroxylase activity in the spontaneously hypertensive rat. The present study examined the effects of antihypertensive drugs (hydrochlorothiazide and guanethidine) on blood pressure and tyrosine hydroxylase (TH) activity in the spontaneously hypertensive rat (SHR). Hydrochlorothiazide (50 mg/kg X 4 days) lowered blood pressure in the SHR to a degree equivalent to that produced by reserpine (0.3 mg/kg X 3 days). However, while reserpine increased vascular and adrenal TH activity, hydrochlorothiazide had no effect. Guanethidine (30 mg/kg X 2 days) reduced blood pressure in the SHR and also depleted cardiac, vascular and adrenal gland catecholamines; However, guanethidine administration did not increase TH activity in the mesenteric vasculature or adrenal glands. These studies indicate that at equieffective blood pressure lowering doses, different antihypertensive drugs have different effects on TH activity in the SHR. Neither blood pressure reduction nor catecholamine depletion in peripheral tissues are sufficient prerequisties for increasing TH activity. The data support the suggestion, however, that amine depletion in the central nervous system or ganglia may be an important factor in the regulation of TH."}
{"id": "PMID:14843", "title": "[Endogenous formation of carcinogenic-N-nitroso compounds in rats after application of drugs and nitrite (author's transl)].", "content": "During the last years in vitro investigations have demonstrated the possibility of nitrosation of different amines and amides including a number of drugs. The aim of the presented investigations was to test whether an endogenous nitrosation of piperazine, Obesin (propyhexedrine), and ephedrine is possible in long term experiments with rats. With the exception of group No. 3, the experiments were carried out with hooded rats (table 1). Group No. 1: 15 rats were given 100 mg/kg b.w. piperazine (Merck, Darmstadt) and 80 mg/kg b.w. NaNO2 by gastric tube. After the fourth application because of intoxication a reduction to 80 mg/kg b.w. piperazine and 50 mg/kg b.w. NaNO2 was necessary. Duration of treatment (in two weeks intervals): 7 months. Group No. 2: Pregnant rats received 80 mg/kg b.w. piperazine and 50 mg/kg b.w. NaNO2 by gastric tube once in the last third of pregnancy. In 13 offsprings the carcinogenic action was tested.  Group No. 3: Pregnant Wistar rats were given 100 mg/kg b.w. piperazine and 70 mg/kg b.w. NaN92 by gastric tube once in the last third of pregnancy. Group No. 4: 20 hooded rats received 40 mg/kg b.w. Obesin (propylhexedrine, Fahlberg-List Magdeburg) and 40 mg/kg b.w. NaM92 once in two weekly intervals by gastric tube. Duration of the treatment: 6 months. 5 controls received 40 mg/kg b.w. Obesin or 40 mg/kg b.w. NaNO2 resp. Group No. 5: Hooded rats were given 40 mg/kg b.w. Obesin and 40 mg/kg b.w. NaNO2 by gastric tube once in the last third of pregnancy. 32 offsprings were observed. Group No. 6: 26 animals received 80 mg/kg b.w. ephedrine (D,L-Ephedrin \"Fahlberg\" DAB 7) and 50 mg/kg b.w. NaNO2 once per two weeks by gastric tube. Duration of the experiment: 6 months. 5 controls were applied 80 mg/kg b.w. ephedrine. Group No. 7: 30 hooded rats received a standard diet containing 0.5 per cent ephedrine and 0.2 per cent NaNO2. Duration of the experiment: 50 days. Only ephedrine was added in the same concentration to the diet of 10 control animals. results (tables 2--7): All animals that survived for more than 80 days were included in the analysis. In group No. 1 after a latency of 254--432 days 5 out of 14 rats developed malignant tumours of the nasal cavities (1), esophagus (1), leukoses (2), or soft tissue sarcoma (1). The spectrum of tumours indicates the endogenous formation of N-nitrosopiperazines. In groups 2 and 3 no significant carcinogenic action can be verified. In 56 per cent of hooded rats of group 4 reticulum-cell sarcomas, that were mainly localized in the paracoecal region (7) as well as leukoses (3) were registered. These findings were regarded as a carcinogenic action of the N-nitroso derivative of Obesin. In group No. 5 there is an insignificant carcinogenic effect. 2 paracoecal reticulum-cell sarcomas, 2 leukoses, 1 soft tissue sarcoma, 1 palsma-cytosis and 1 spindle cell sarcoma of the heart were found. After application of ephedrine and nitrite in group No. 6 and group No...", "contents": "[Endogenous formation of carcinogenic-N-nitroso compounds in rats after application of drugs and nitrite (author's transl)]. During the last years in vitro investigations have demonstrated the possibility of nitrosation of different amines and amides including a number of drugs. The aim of the presented investigations was to test whether an endogenous nitrosation of piperazine, Obesin (propyhexedrine), and ephedrine is possible in long term experiments with rats. With the exception of group No. 3, the experiments were carried out with hooded rats (table 1). Group No. 1: 15 rats were given 100 mg/kg b.w. piperazine (Merck, Darmstadt) and 80 mg/kg b.w. NaNO2 by gastric tube. After the fourth application because of intoxication a reduction to 80 mg/kg b.w. piperazine and 50 mg/kg b.w. NaNO2 was necessary. Duration of treatment (in two weeks intervals): 7 months. Group No. 2: Pregnant rats received 80 mg/kg b.w. piperazine and 50 mg/kg b.w. NaNO2 by gastric tube once in the last third of pregnancy. In 13 offsprings the carcinogenic action was tested.  Group No. 3: Pregnant Wistar rats were given 100 mg/kg b.w. piperazine and 70 mg/kg b.w. NaN92 by gastric tube once in the last third of pregnancy. Group No. 4: 20 hooded rats received 40 mg/kg b.w. Obesin (propylhexedrine, Fahlberg-List Magdeburg) and 40 mg/kg b.w. NaM92 once in two weekly intervals by gastric tube. Duration of the treatment: 6 months. 5 controls received 40 mg/kg b.w. Obesin or 40 mg/kg b.w. NaNO2 resp. Group No. 5: Hooded rats were given 40 mg/kg b.w. Obesin and 40 mg/kg b.w. NaNO2 by gastric tube once in the last third of pregnancy. 32 offsprings were observed. Group No. 6: 26 animals received 80 mg/kg b.w. ephedrine (D,L-Ephedrin \"Fahlberg\" DAB 7) and 50 mg/kg b.w. NaNO2 once per two weeks by gastric tube. Duration of the experiment: 6 months. 5 controls were applied 80 mg/kg b.w. ephedrine. Group No. 7: 30 hooded rats received a standard diet containing 0.5 per cent ephedrine and 0.2 per cent NaNO2. Duration of the experiment: 50 days. Only ephedrine was added in the same concentration to the diet of 10 control animals. results (tables 2--7): All animals that survived for more than 80 days were included in the analysis. In group No. 1 after a latency of 254--432 days 5 out of 14 rats developed malignant tumours of the nasal cavities (1), esophagus (1), leukoses (2), or soft tissue sarcoma (1). The spectrum of tumours indicates the endogenous formation of N-nitrosopiperazines. In groups 2 and 3 no significant carcinogenic action can be verified. In 56 per cent of hooded rats of group 4 reticulum-cell sarcomas, that were mainly localized in the paracoecal region (7) as well as leukoses (3) were registered. These findings were regarded as a carcinogenic action of the N-nitroso derivative of Obesin. In group No. 5 there is an insignificant carcinogenic effect. 2 paracoecal reticulum-cell sarcomas, 2 leukoses, 1 soft tissue sarcoma, 1 palsma-cytosis and 1 spindle cell sarcoma of the heart were found. After application of ephedrine and nitrite in group No. 6 and group No..."}
{"id": "PMID:14844", "title": "Activity of two components of serum ribonuclease under conditions of physical exercise.", "content": "Serum ribonuclease activity before and after physical exercise in healthy persons was estimated. It is found that a work load of 6000 kgm/5 min increased ribonuclease activity measured at pH 8.5 and decreased the activity of the same enzyme measured at pH 7.0 in the presence of Zn SO4. The observed changes were more pronounced in untrained than in trained persons.", "contents": "Activity of two components of serum ribonuclease under conditions of physical exercise. Serum ribonuclease activity before and after physical exercise in healthy persons was estimated. It is found that a work load of 6000 kgm/5 min increased ribonuclease activity measured at pH 8.5 and decreased the activity of the same enzyme measured at pH 7.0 in the presence of Zn SO4. The observed changes were more pronounced in untrained than in trained persons."}
{"id": "PMID:14845", "title": "Effect of various factors on the activity of trehalase from the larvae of Sesamia inferens Walker (Insect).", "content": "Trehalase from the salivary glands and the midgut of Sesamia inferens showed optimum activity at pH 5.8, and at temperatures of 50 and 60 degrees C respectively. The increase in the incubation period, enzyme concentration, and substrate concentration respectively increased the end-product, the hydrolysis, and the rate of hydrolysis of the substrate. Dialysis did not affect, tryptophan accelerated, and other amino acids and end-product inhibited the enzyme activity.", "contents": "Effect of various factors on the activity of trehalase from the larvae of Sesamia inferens Walker (Insect). Trehalase from the salivary glands and the midgut of Sesamia inferens showed optimum activity at pH 5.8, and at temperatures of 50 and 60 degrees C respectively. The increase in the incubation period, enzyme concentration, and substrate concentration respectively increased the end-product, the hydrolysis, and the rate of hydrolysis of the substrate. Dialysis did not affect, tryptophan accelerated, and other amino acids and end-product inhibited the enzyme activity."}
{"id": "PMID:14849", "title": "Oxygen and carbon dioxide in the regulation of respiration.", "content": "When a sea-level resident ascends to a high altitude, his breathing immediately increases because of hypoxic stimulation of the peripheral chemoreceptors. In many species the aortic bodies are relatively unimportant in this response compared to the carotid bodies. When the subject stays at that altitude, his breathing increases progressively in the next few hours and days in a process termed ventilatory acclimatization and does not immediately return to control levels when hypoxia is terminated. Evidence is summarized indicating that this chronic process does not depend on the peripheral chemoreceptors or an initial respiratory alkalosis. Historical review indicates that the process of ventilatory acclimatization was initially attributed to renal excretion of plasma bicarbonate with development of a metabolic acidosis; but subsequent measurements indicated this process did not lower the arterial pH sufficiently to account for the ventilatory stimulation. More recently, ventilatory acclimatization has been attributed to accelerated removal of bicarbonate from the cerebrospinal fluid (CSF), producing a metabolic acidosis in the region of the medullary chemoreceptors; but still more recent observations indicate that this process, contrary to earlier observations, does not lower the CSF pH sufficiently to account for the ventilatory stimulation, either. Some other mechanism should be sought.", "contents": "Oxygen and carbon dioxide in the regulation of respiration. When a sea-level resident ascends to a high altitude, his breathing immediately increases because of hypoxic stimulation of the peripheral chemoreceptors. In many species the aortic bodies are relatively unimportant in this response compared to the carotid bodies. When the subject stays at that altitude, his breathing increases progressively in the next few hours and days in a process termed ventilatory acclimatization and does not immediately return to control levels when hypoxia is terminated. Evidence is summarized indicating that this chronic process does not depend on the peripheral chemoreceptors or an initial respiratory alkalosis. Historical review indicates that the process of ventilatory acclimatization was initially attributed to renal excretion of plasma bicarbonate with development of a metabolic acidosis; but subsequent measurements indicated this process did not lower the arterial pH sufficiently to account for the ventilatory stimulation. More recently, ventilatory acclimatization has been attributed to accelerated removal of bicarbonate from the cerebrospinal fluid (CSF), producing a metabolic acidosis in the region of the medullary chemoreceptors; but still more recent observations indicate that this process, contrary to earlier observations, does not lower the CSF pH sufficiently to account for the ventilatory stimulation, either. Some other mechanism should be sought."}
{"id": "PMID:14850", "title": "New developments in our knowledge of the chemistry of renin.", "content": "Although the role of renin in hypertension continues to be incompletely defined, recent progress in the chemistry of renin has been considerable. Extensive purifications of hog kidney renin and the renin-like mouse submaxillary gland enzyme have been achieved. Various inhibitory peptides based on tetradecapeptide renin substrate have been useful in renin kinetic studies and in renin affinity chromatography. Classification of renin as an acid protease results from its marked inhibition by pepstatin and from the discovery that free carboxyl at the active site is essential for activity in human and hog kidney and mouse submaxillary gland enzymes. The presence of pseudorenin in all tissues has limited the use of model peptides as renin substrates in plasma and crude tissue extracts, since the proteolytic properties of the two enzymes are nearly identical. The existence of renin in multiple, chromatographically separable forms has been known. More recently inactive forms have been found in plasma, amniotic fluid, and hog and rabbit kidneys. Prolonged storage or treatment with acid, trypsin, or pepsin causes activation; in some instances the conversion is from a higher than normal molecular weight. The implications of these findings with respect to the renin-angiotensin system need much further investigation.", "contents": "New developments in our knowledge of the chemistry of renin. Although the role of renin in hypertension continues to be incompletely defined, recent progress in the chemistry of renin has been considerable. Extensive purifications of hog kidney renin and the renin-like mouse submaxillary gland enzyme have been achieved. Various inhibitory peptides based on tetradecapeptide renin substrate have been useful in renin kinetic studies and in renin affinity chromatography. Classification of renin as an acid protease results from its marked inhibition by pepstatin and from the discovery that free carboxyl at the active site is essential for activity in human and hog kidney and mouse submaxillary gland enzymes. The presence of pseudorenin in all tissues has limited the use of model peptides as renin substrates in plasma and crude tissue extracts, since the proteolytic properties of the two enzymes are nearly identical. The existence of renin in multiple, chromatographically separable forms has been known. More recently inactive forms have been found in plasma, amniotic fluid, and hog and rabbit kidneys. Prolonged storage or treatment with acid, trypsin, or pepsin causes activation; in some instances the conversion is from a higher than normal molecular weight. The implications of these findings with respect to the renin-angiotensin system need much further investigation."}
{"id": "PMID:14851", "title": "[Enzymatic processes and chemical composition of the cecal contents of swine fed carbohydrates from different plants].", "content": "A considerable amount of low-molecular acids (14.5-18.2 meqv/100 ml) is formed in the coecum in consequence of fermentation of cellulose, starch, and other components of chyme with microflora. The total concentration and molecular per cent ratio of the acetic, propionic, butyric, and lactic acids depended on the composition of the carbohydrate ration.", "contents": "[Enzymatic processes and chemical composition of the cecal contents of swine fed carbohydrates from different plants]. A considerable amount of low-molecular acids (14.5-18.2 meqv/100 ml) is formed in the coecum in consequence of fermentation of cellulose, starch, and other components of chyme with microflora. The total concentration and molecular per cent ratio of the acetic, propionic, butyric, and lactic acids depended on the composition of the carbohydrate ration."}
{"id": "PMID:14852", "title": "Time dependence of the effect of splenectomy on graft-versus-host reactivity of lymph node cells.", "content": "Changes in cell-mediated reactivity of lymph node cells at various intervals after splenectomy were investigated in three assays measuring the GVH reactivity of parental cells in F1 hybrids --splenomegaly test in very young recipients and popliteal lymph node enlargement assay in adults measuring the proliferative component of the reaction, and mortality assay in sublethally irradiated recipients measuring the killer activity of the cell inoculum. During the early postsplenectomy period the reactivity of the particular amounts of lymph node cells was lower than that of cells from normal donors, but at about 3 weeks after splenectomy it was higher. The increase was of short duration in the proliferation assay and at 5 weeks the reactivity declined markedly below the control values. The increase in activity persisted for 5 weeks after splenectomy in the \"killer\" assay. It is probable that the described changes in cell-mediated reactivity are involved in the total effect of splenectomy on the host's complex immune response, especially against normal and tumour allografts.", "contents": "Time dependence of the effect of splenectomy on graft-versus-host reactivity of lymph node cells. Changes in cell-mediated reactivity of lymph node cells at various intervals after splenectomy were investigated in three assays measuring the GVH reactivity of parental cells in F1 hybrids --splenomegaly test in very young recipients and popliteal lymph node enlargement assay in adults measuring the proliferative component of the reaction, and mortality assay in sublethally irradiated recipients measuring the killer activity of the cell inoculum. During the early postsplenectomy period the reactivity of the particular amounts of lymph node cells was lower than that of cells from normal donors, but at about 3 weeks after splenectomy it was higher. The increase was of short duration in the proliferation assay and at 5 weeks the reactivity declined markedly below the control values. The increase in activity persisted for 5 weeks after splenectomy in the \"killer\" assay. It is probable that the described changes in cell-mediated reactivity are involved in the total effect of splenectomy on the host's complex immune response, especially against normal and tumour allografts."}
{"id": "PMID:14858", "title": "Aversive prenatal stimulation: effects on behavioral, biochemical, and somatic ontogeny in the rat.", "content": "Electric foot shock administered to pregnant rats altered the ontogeny of spontaneous motor activity in their pups. Prenatally stimulated (PMS) offspring were more active than controls on Days 1-10 but less active during the 3rd postpartum week. The age of peak activity, a major developmental landmark, occurred in PMS pups around 10 days of age; in controls maximum activity was not seen until the 3rd week. This effect was independent of the gender of the offspring and the timing of the gestational stimulation. Its appearance in both cross-fostered and fostered pups indicated the prenatal origin of the effect. The maturation of spontaneous alternation behavior and several reflexes and the appearance of physical features were not affected by prenatal stimulation. Moreover, both PMS and control groups exhibited an age-related increase in brain concentrations of norepinephrine, serotonin, and 5-hydroxyindoleacetic acid. These findings indicate that spontaneous motor activity is uniquely sensitive to PMS, and as far as can be determined here, PMS produces no generalized alteration in behavioral and physical ontogeny.", "contents": "Aversive prenatal stimulation: effects on behavioral, biochemical, and somatic ontogeny in the rat. Electric foot shock administered to pregnant rats altered the ontogeny of spontaneous motor activity in their pups. Prenatally stimulated (PMS) offspring were more active than controls on Days 1-10 but less active during the 3rd postpartum week. The age of peak activity, a major developmental landmark, occurred in PMS pups around 10 days of age; in controls maximum activity was not seen until the 3rd week. This effect was independent of the gender of the offspring and the timing of the gestational stimulation. Its appearance in both cross-fostered and fostered pups indicated the prenatal origin of the effect. The maturation of spontaneous alternation behavior and several reflexes and the appearance of physical features were not affected by prenatal stimulation. Moreover, both PMS and control groups exhibited an age-related increase in brain concentrations of norepinephrine, serotonin, and 5-hydroxyindoleacetic acid. These findings indicate that spontaneous motor activity is uniquely sensitive to PMS, and as far as can be determined here, PMS produces no generalized alteration in behavioral and physical ontogeny."}
{"id": "PMID:14859", "title": "Decreased rat hepatic guanylate cyclase activity in streptozotocin-induced diabetes mellitus.", "content": "Guanylate cyclase is found in virtually all cells, but its physiologic role and the effect of hormones on its activity have not been clarified. Hepatic soluble guanylate cyclase activity (37,000 g supernatant) in rats with diabetes-mellitus-like syndrome induced by streptozotocin, 65 mg./kg. i.v., was 140 +/- 8 pmoles accumulated/mg. protein/10 min. (n = 13 rats) as against 279 +/- 16 pmoles accumulated/mg. protein/10 min. (n = 12 rats) in normal rats. The average blood sugar for the 12 normal rats was 100 +/- 4 mg./100 ml. and 546 +/- 32 mg./100 ml. for 13 diabetic rats. The decreased soluble hepatic guanylate cyclase activity in diabetic rats was completely restored to normal with 10 U. regular insulin, i.p. The maximum increase in guanylate cyclase activity was observed as early as five minutes and as late as two hours after insulin administration. Insulin restoration of guanylate cyclase was dose-related over a range of 1 U. to 10 U., i.p. Hepatic cyclic GMP levels in vivo paralleled in-vitro guanylate cyclase activity, being 29 +/- 0.4 pmoles/gm. wet weight in normals, 17 +/- 0.4 pmoles/gm. wet weight in streptozotocin-diabetic rats, and 38 +/- 0.4 pmoles/gm. wet weight two hours after the injection of 10 U. regular insulin. We conclude that rat hepatic guanylate cyclase is decreased in streptozotocin-induced diabetes and that insulin modulates this enzyme. The administration of exogenous insulin in normal animals did not further augment hepatic guanylate cyclase activity.", "contents": "Decreased rat hepatic guanylate cyclase activity in streptozotocin-induced diabetes mellitus. Guanylate cyclase is found in virtually all cells, but its physiologic role and the effect of hormones on its activity have not been clarified. Hepatic soluble guanylate cyclase activity (37,000 g supernatant) in rats with diabetes-mellitus-like syndrome induced by streptozotocin, 65 mg./kg. i.v., was 140 +/- 8 pmoles accumulated/mg. protein/10 min. (n = 13 rats) as against 279 +/- 16 pmoles accumulated/mg. protein/10 min. (n = 12 rats) in normal rats. The average blood sugar for the 12 normal rats was 100 +/- 4 mg./100 ml. and 546 +/- 32 mg./100 ml. for 13 diabetic rats. The decreased soluble hepatic guanylate cyclase activity in diabetic rats was completely restored to normal with 10 U. regular insulin, i.p. The maximum increase in guanylate cyclase activity was observed as early as five minutes and as late as two hours after insulin administration. Insulin restoration of guanylate cyclase was dose-related over a range of 1 U. to 10 U., i.p. Hepatic cyclic GMP levels in vivo paralleled in-vitro guanylate cyclase activity, being 29 +/- 0.4 pmoles/gm. wet weight in normals, 17 +/- 0.4 pmoles/gm. wet weight in streptozotocin-diabetic rats, and 38 +/- 0.4 pmoles/gm. wet weight two hours after the injection of 10 U. regular insulin. We conclude that rat hepatic guanylate cyclase is decreased in streptozotocin-induced diabetes and that insulin modulates this enzyme. The administration of exogenous insulin in normal animals did not further augment hepatic guanylate cyclase activity."}
{"id": "PMID:14860", "title": "Aspects of carbohydrate metabolism in developing brain.", "content": "This review considers carbohydrate metabolism in the developing brain, in particular the proportion of glucose metabolized via the pentose phosphate pathway. Although small in amount, this fraction serves a vital r\u00f4le in some aspects of brain function. Evidence is presented that the pentose phosphate pathway subserves different functions as the developing brain progresses through the stages of growth and myelination to full neurological competence. The general aspects considered are the changing patterns of brain enzymes during development; the flux of glucose through the alternative pathways of glucose metabolism in the developing brain; the functional significance of the pentose phosphate pathway; and the regional and functional association of the pentose phosphate pathway activity and the detoxication of biogenic am\u00ednes.", "contents": "Aspects of carbohydrate metabolism in developing brain. This review considers carbohydrate metabolism in the developing brain, in particular the proportion of glucose metabolized via the pentose phosphate pathway. Although small in amount, this fraction serves a vital r\u00f4le in some aspects of brain function. Evidence is presented that the pentose phosphate pathway subserves different functions as the developing brain progresses through the stages of growth and myelination to full neurological competence. The general aspects considered are the changing patterns of brain enzymes during development; the flux of glucose through the alternative pathways of glucose metabolism in the developing brain; the functional significance of the pentose phosphate pathway; and the regional and functional association of the pentose phosphate pathway activity and the detoxication of biogenic am\u00ednes."}
{"id": "PMID:14861", "title": "Serum gastrin levels before and after 6 weeks of cimetidine therapy in patients with duodenal ulcer.", "content": "Fasting serum gastrins were carried out at the beginning and end of a 6-week double-blind trial of cimetidine and placebo in 30 patients with duodenal ulcer. Cimetidine did not cause any significant change in fasting serum gastrin levels after 6 weeks of therapy.", "contents": "Serum gastrin levels before and after 6 weeks of cimetidine therapy in patients with duodenal ulcer. Fasting serum gastrins were carried out at the beginning and end of a 6-week double-blind trial of cimetidine and placebo in 30 patients with duodenal ulcer. Cimetidine did not cause any significant change in fasting serum gastrin levels after 6 weeks of therapy."}
{"id": "PMID:14862", "title": "The effect of the alkaline tide on serum-ionized calcium concentration in man.", "content": "The effect of the gastric alkaline tide on serum-ionized calcium levels was determined in human subjects. Gastric acid seretion was stimulated by a standard steak meal, human synthetic gastrin, and betazole hydrochloride. Ionized calcium levels fell to a similar extent after each stimulus. The mean decrease in calcium ion concentration in all experiments was 5.4% of the basal concentration. The fall in serum calcium ion concentration was highly correlated with the rise in serum pH. We speculate that increased formation of calcium bicarbonate complex in the serum as well as increased binding of ionized calcium by serum protein accounts for the surprisingly large effect of the alkaline tide on serumionized calcium levels.", "contents": "The effect of the alkaline tide on serum-ionized calcium concentration in man. The effect of the gastric alkaline tide on serum-ionized calcium levels was determined in human subjects. Gastric acid seretion was stimulated by a standard steak meal, human synthetic gastrin, and betazole hydrochloride. Ionized calcium levels fell to a similar extent after each stimulus. The mean decrease in calcium ion concentration in all experiments was 5.4% of the basal concentration. The fall in serum calcium ion concentration was highly correlated with the rise in serum pH. We speculate that increased formation of calcium bicarbonate complex in the serum as well as increased binding of ionized calcium by serum protein accounts for the surprisingly large effect of the alkaline tide on serumionized calcium levels."}
{"id": "PMID:14865", "title": "Lower esophageal sphincter pressure in cirrhotic men with ascites: before and after diuresis.", "content": "Lower esophageal sphincter pressure (LESP) was measured in 10 biopsy-proved cirrhotics with esophageal varices and tense ascites before and after diuresis to evaluate of ascites might play in the development of variceal bleeding. In the 10 cirrhotic men studied, basal LESP was 30.9 +/- 1.7 mm Hg before and 22.7 +/- 1.3 mm Hg (P less than 0.01) after a diuresis which resulted in a mean 12-kg weight loss. LESP responses to abdominal compression were also evaluated. The change in LESP in response to a standard degree of abdominal compression was greater in the presence of ascites (8.5 +/- 0.4) than in its absence (6.3 +/- 0.4) (P less than 0.01). Basal gastric pH and fasting plasma gastrin concentrations did not differ during the two testing periods. Based on these data and the rarity with which cirrhotic patients with ascites complain of heartburn, it is concluded that reflux esophagitis caused by failure of the lower esophageal sphincter to remain competent is unlikely to be a significant etiological factor in the development of variceal bleeding.", "contents": "Lower esophageal sphincter pressure in cirrhotic men with ascites: before and after diuresis. Lower esophageal sphincter pressure (LESP) was measured in 10 biopsy-proved cirrhotics with esophageal varices and tense ascites before and after diuresis to evaluate of ascites might play in the development of variceal bleeding. In the 10 cirrhotic men studied, basal LESP was 30.9 +/- 1.7 mm Hg before and 22.7 +/- 1.3 mm Hg (P less than 0.01) after a diuresis which resulted in a mean 12-kg weight loss. LESP responses to abdominal compression were also evaluated. The change in LESP in response to a standard degree of abdominal compression was greater in the presence of ascites (8.5 +/- 0.4) than in its absence (6.3 +/- 0.4) (P less than 0.01). Basal gastric pH and fasting plasma gastrin concentrations did not differ during the two testing periods. Based on these data and the rarity with which cirrhotic patients with ascites complain of heartburn, it is concluded that reflux esophagitis caused by failure of the lower esophageal sphincter to remain competent is unlikely to be a significant etiological factor in the development of variceal bleeding."}
{"id": "PMID:14866", "title": "Small intestinal injury in the graft versus host reaction: an innocent bystander phenomenon.", "content": "Marked morphological and functional damage to the small intestine occurs during the graft versus host reaction (GVHR); the structural lesion is characterized by crypt hypertrophy and villus shortening. The purpose of this study was to determine whether the intestine is injured in the GVHR as an antigenic target of the grafted immunocompetent cells or as an innocent bystander to donor-host lymphoid interaction. Implants of fetal mouse small intestine from either C57BL/6 or (C57BL/L X DBA/2)F1 (BDF1) hybrid donors were placed under the kidney capsule of adult BDF1 male mice. After 4 weeks, both groups were injected with parental C57BL/6 spleen cells, syngeneic BDF1 spleen cells, or no cells. Two weeks after injection the mice were killed and the implants were removed for histological processing and measurement of villus height and crypt depth. The villus-crypt ratio in the BDF1 implants of mice receiving C57BL/6 cells was 1.32 +/- 0.3 compared to 2.51 +/- 0.4 in controls receiving either syngeneic BDF1 cells or no cells (P less than 0.001). The villus-crypt ratio in the C57BL/6 implants of mice receiving C57BL/6 cells was 1.79 +/- 0.4 compared to 2.48 +/- 0.4 in the controls receiving either syngeneic BDF1 cells or no cells (P less than 0.001). Because the latter implant is antigenically identical to the spleen cells eliciting the GVHR, we conclude that the small bowel is injured in the GVHR as an innocent bystander to cytotoxic donor-host lymphoid interaction.", "contents": "Small intestinal injury in the graft versus host reaction: an innocent bystander phenomenon. Marked morphological and functional damage to the small intestine occurs during the graft versus host reaction (GVHR); the structural lesion is characterized by crypt hypertrophy and villus shortening. The purpose of this study was to determine whether the intestine is injured in the GVHR as an antigenic target of the grafted immunocompetent cells or as an innocent bystander to donor-host lymphoid interaction. Implants of fetal mouse small intestine from either C57BL/6 or (C57BL/L X DBA/2)F1 (BDF1) hybrid donors were placed under the kidney capsule of adult BDF1 male mice. After 4 weeks, both groups were injected with parental C57BL/6 spleen cells, syngeneic BDF1 spleen cells, or no cells. Two weeks after injection the mice were killed and the implants were removed for histological processing and measurement of villus height and crypt depth. The villus-crypt ratio in the BDF1 implants of mice receiving C57BL/6 cells was 1.32 +/- 0.3 compared to 2.51 +/- 0.4 in controls receiving either syngeneic BDF1 cells or no cells (P less than 0.001). The villus-crypt ratio in the C57BL/6 implants of mice receiving C57BL/6 cells was 1.79 +/- 0.4 compared to 2.48 +/- 0.4 in the controls receiving either syngeneic BDF1 cells or no cells (P less than 0.001). Because the latter implant is antigenically identical to the spleen cells eliciting the GVHR, we conclude that the small bowel is injured in the GVHR as an innocent bystander to cytotoxic donor-host lymphoid interaction."}
{"id": "PMID:14867", "title": "Stimulatory (H1) and inhibitory (H2) histamine receptors in gallbladder muscle.", "content": "The nature of histamine receptors in gallbladder muscle and examined using specific histamine-receptor agonists and antagonists. The H2-receptor antagonist, metiamide, augmented the contractile response to histamine indicating that gallbladder muscle possessed stimulatory H1 receptors and inhibitory H2 receptors. The independent inhibitory character of H2 receptors was confirmed by (1) induction of relaxation with histamine after H1-receptor blockade and the suppression of this relaxation with metiamide, and (2) induction of relaxation with a specific H2-receptor agonist, 4-methyl histamine and the suppression of this relaxation with metiamide. Further, blockade of H2 but not of H1 receptors augmented the response to the octapeptide of cholecystokinin. The nature of this effect was such that the apparent affinity of the octapeptide for its own receptor was increased. The finding raised the possibility that in their native unoccupied state, H2 receptors may modify the response to hormonal agents.", "contents": "Stimulatory (H1) and inhibitory (H2) histamine receptors in gallbladder muscle. The nature of histamine receptors in gallbladder muscle and examined using specific histamine-receptor agonists and antagonists. The H2-receptor antagonist, metiamide, augmented the contractile response to histamine indicating that gallbladder muscle possessed stimulatory H1 receptors and inhibitory H2 receptors. The independent inhibitory character of H2 receptors was confirmed by (1) induction of relaxation with histamine after H1-receptor blockade and the suppression of this relaxation with metiamide, and (2) induction of relaxation with a specific H2-receptor agonist, 4-methyl histamine and the suppression of this relaxation with metiamide. Further, blockade of H2 but not of H1 receptors augmented the response to the octapeptide of cholecystokinin. The nature of this effect was such that the apparent affinity of the octapeptide for its own receptor was increased. The finding raised the possibility that in their native unoccupied state, H2 receptors may modify the response to hormonal agents."}
{"id": "PMID:14870", "title": "[Pharmacological analysis of effects of perimetazine on isolated smooth muscle].", "content": "Effects of perimetazine on the motility of the isolated smooth muscle of guinea pig (ileum, taenia coli, uterus, vas deferens and trachea) and the ileum of rabbit were studied. The results obtained are as follows: Perimetazine showed a specific antihistamine, antiadrenaline and antiserotonin action. Moreover, antiacetylcholine and anti-BaC12 actions were observed with high doses of perimetazine as well as chlorpromazine and such actions were attributed to the nonspecific direct action on the smooth muscle. Both the spontaneous movement and the tonus of guinea pig taenia coli were also inhibited by a high concentration of perimetazine. The spontaneous membrane action potentials of the taenia coli recorded by the use of the sucrose-gap method were inhibited by a high concentration of perimetazine both in frequency and in amplitude with relaxation of the tonus. The action potentials were abolished however and change in the resting membrane level was not clearly observed.", "contents": "[Pharmacological analysis of effects of perimetazine on isolated smooth muscle]. Effects of perimetazine on the motility of the isolated smooth muscle of guinea pig (ileum, taenia coli, uterus, vas deferens and trachea) and the ileum of rabbit were studied. The results obtained are as follows: Perimetazine showed a specific antihistamine, antiadrenaline and antiserotonin action. Moreover, antiacetylcholine and anti-BaC12 actions were observed with high doses of perimetazine as well as chlorpromazine and such actions were attributed to the nonspecific direct action on the smooth muscle. Both the spontaneous movement and the tonus of guinea pig taenia coli were also inhibited by a high concentration of perimetazine. The spontaneous membrane action potentials of the taenia coli recorded by the use of the sucrose-gap method were inhibited by a high concentration of perimetazine both in frequency and in amplitude with relaxation of the tonus. The action potentials were abolished however and change in the resting membrane level was not clearly observed."}
{"id": "PMID:14871", "title": "[Findings in the gastric mucosa and gastric secretion in rats treated with methyl O-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400) and reserpine derivatives].", "content": "CD-3400 developed by Nippon Chemiphar Co. Ltd., is a new antihypertensive agent belonging to the class of rauwolfa alkaloids. Influence of the agent on gastric mucosa, healing process of acetic acid-induced gastric ulcer and gastric juice in rats was investigated and compared with effects of reserpine and rescinnamine. CD-3400-induced gastric lesions were fewer in number than those produced with reserpine and rescinnamine in fasted rats. After a three day treatment of CD-3400 to fed rats, however, there were few gastric lesions, while reserpine- and rescinnamine-induced gastric lesions were aggravated to a greater extent that when a single administration was given to fasted rats. Influence of CD-3400, reserpine and rescinnamine on the healing process of acetic acid-induced ulcer was insignificant, but treatment with high doses of reserpine and rescinnamine resulted in death. Pretreatment with CD-3400 and reserpine produced a decrease in gastric acid and K+, and an increase in Na+. Repeated administration of reserpine for 5 days resulted in a decrease of both gastric volume and acid, while such was not seen with CD-3400. Treatment with anticholinergic agents such as atropine sulfate and atropine methylbromide inhibited CD-3400- and reserpine-induced gastric lesions. From these results, it would appear that cholinergic factors play a role in the pathogenesis of CD-3400-induced gastric lesions, as in the case with reserpine, and that the responses of these lesions to reserpine and CD-3400 correlate with changes of ionic fluxes in gastric juice.", "contents": "[Findings in the gastric mucosa and gastric secretion in rats treated with methyl O-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400) and reserpine derivatives]. CD-3400 developed by Nippon Chemiphar Co. Ltd., is a new antihypertensive agent belonging to the class of rauwolfa alkaloids. Influence of the agent on gastric mucosa, healing process of acetic acid-induced gastric ulcer and gastric juice in rats was investigated and compared with effects of reserpine and rescinnamine. CD-3400-induced gastric lesions were fewer in number than those produced with reserpine and rescinnamine in fasted rats. After a three day treatment of CD-3400 to fed rats, however, there were few gastric lesions, while reserpine- and rescinnamine-induced gastric lesions were aggravated to a greater extent that when a single administration was given to fasted rats. Influence of CD-3400, reserpine and rescinnamine on the healing process of acetic acid-induced ulcer was insignificant, but treatment with high doses of reserpine and rescinnamine resulted in death. Pretreatment with CD-3400 and reserpine produced a decrease in gastric acid and K+, and an increase in Na+. Repeated administration of reserpine for 5 days resulted in a decrease of both gastric volume and acid, while such was not seen with CD-3400. Treatment with anticholinergic agents such as atropine sulfate and atropine methylbromide inhibited CD-3400- and reserpine-induced gastric lesions. From these results, it would appear that cholinergic factors play a role in the pathogenesis of CD-3400-induced gastric lesions, as in the case with reserpine, and that the responses of these lesions to reserpine and CD-3400 correlate with changes of ionic fluxes in gastric juice."}
{"id": "PMID:14872", "title": "[Effects of methyl O-(4-hydroxy-3-methoxycinnamoly)reserpate (CD-3400) on the peripheral nervous system: especially on the smooth muscle organs].", "content": "Effects of methyl O-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400), a new antihypertensive agent, on the peripheral nervous system in mice, rats and guinea pigs were investigated and compared with effects of reserpine and rescinnamine. Oral administration of CD-3400 in doses from 40 to 320 mg/kg revealed a miotic action and such was weaker than that seen with reserpine and rescinnamine. The intestinal propulsion in mice was accelerated by pretreatment with reserpine, but no so with CD-3400. In isolated guinea pig vas deferens, CD-3400 at a concentration of 1 X 10(-5) M inhibited on norepinephrine-induced contraction non-competitively. However, in insolated rat vas deferens pretreated with CD-3400 (1 mg/kg, i.p.) for 5 days, norepinephrine-induced contraction was potentiated and this effect was weaker than that seen with reserpine and rescinnamine. In isolated rat vas deferens pretreated with CD-3400 for 1, 2 and 5 days,, the contraction induced by tyramine (3 X 10(-5)M) was significantly inhibited. The effect was qualitively similar to those of reserpine and rescinnamine. The intravenous administration of these three rauwolfia alkaloids in doses of 1, 2 and 4 mg/kg had no effect on the spontaneous movement of rat uterus. In isolated rat uterus pretreated with CD-3400, no significant effect was observed on oxytocin- and isoproterenol-induced responses. The peripheral actions of CD-3400 are attributed to a deterioration in the function the sympathetic nerve resulting in depletion of catecholamine stores. Efect of CD-3400 were slightly weaker than those of reserpine and rescinnamine.", "contents": "[Effects of methyl O-(4-hydroxy-3-methoxycinnamoly)reserpate (CD-3400) on the peripheral nervous system: especially on the smooth muscle organs]. Effects of methyl O-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400), a new antihypertensive agent, on the peripheral nervous system in mice, rats and guinea pigs were investigated and compared with effects of reserpine and rescinnamine. Oral administration of CD-3400 in doses from 40 to 320 mg/kg revealed a miotic action and such was weaker than that seen with reserpine and rescinnamine. The intestinal propulsion in mice was accelerated by pretreatment with reserpine, but no so with CD-3400. In isolated guinea pig vas deferens, CD-3400 at a concentration of 1 X 10(-5) M inhibited on norepinephrine-induced contraction non-competitively. However, in insolated rat vas deferens pretreated with CD-3400 (1 mg/kg, i.p.) for 5 days, norepinephrine-induced contraction was potentiated and this effect was weaker than that seen with reserpine and rescinnamine. In isolated rat vas deferens pretreated with CD-3400 for 1, 2 and 5 days,, the contraction induced by tyramine (3 X 10(-5)M) was significantly inhibited. The effect was qualitively similar to those of reserpine and rescinnamine. The intravenous administration of these three rauwolfia alkaloids in doses of 1, 2 and 4 mg/kg had no effect on the spontaneous movement of rat uterus. In isolated rat uterus pretreated with CD-3400, no significant effect was observed on oxytocin- and isoproterenol-induced responses. The peripheral actions of CD-3400 are attributed to a deterioration in the function the sympathetic nerve resulting in depletion of catecholamine stores. Efect of CD-3400 were slightly weaker than those of reserpine and rescinnamine."}
{"id": "PMID:14873", "title": "Separation and properties of alpha-mannosidase and mannanase from the basidiomycete Phellinus abietis.", "content": "Proteins of a crude enzyme preparation obtained from the cultivation medium of the basidiomycete Phellinus abietis were separated by gel filtration and ion-exchange chromatography. The preparation contained a minimum of three enzymes capable of splitting alpha-D-mannosidic bonds: alpha-mannosidase, exomannanase, and endomannanase, which were separated. Some properties of the mannanase complex of the crude enzyme preparation, and of a partially purified alpha-mannosidase were examined. The mannanase complex exhibited two pH optima, its temperature optimum being at 45 degrees C. The pH optimum of purified alpha-mannosidase was at pH 5.0, the temperature optimum being at 45 degrees C. The pH optimum of purifed alpha-mannosidase was at pH 5.0, the temperature optimum at at 60 degrees C; the enzyme had a relatively high heat stability. The Km of alpha-mannosidase for p-nitrophenyl alpha-D-mannopyranoside was 1.5 X 10(-5) M. Pure alpha-mannosidase did not split mannan.", "contents": "Separation and properties of alpha-mannosidase and mannanase from the basidiomycete Phellinus abietis. Proteins of a crude enzyme preparation obtained from the cultivation medium of the basidiomycete Phellinus abietis were separated by gel filtration and ion-exchange chromatography. The preparation contained a minimum of three enzymes capable of splitting alpha-D-mannosidic bonds: alpha-mannosidase, exomannanase, and endomannanase, which were separated. Some properties of the mannanase complex of the crude enzyme preparation, and of a partially purified alpha-mannosidase were examined. The mannanase complex exhibited two pH optima, its temperature optimum being at 45 degrees C. The pH optimum of purified alpha-mannosidase was at pH 5.0, the temperature optimum being at 45 degrees C. The pH optimum of purifed alpha-mannosidase was at pH 5.0, the temperature optimum at at 60 degrees C; the enzyme had a relatively high heat stability. The Km of alpha-mannosidase for p-nitrophenyl alpha-D-mannopyranoside was 1.5 X 10(-5) M. Pure alpha-mannosidase did not split mannan."}
{"id": "PMID:14874", "title": "[A new method for the clinical determination of urinary porphobilinogen and delta-aminolevulinic acid].", "content": "A new method has been developed for clinical determination of porphobilinogen and delta-aminolevulinic acid in urine. Compared with the method of Mauzerall and Granick, being the most commonly used method for clinical application, there is an essential reduction of work and needed time. During the flow of 0.5 ml urine on a 0.7 cm x 2 cm column of macroporous cation exchange resin in H+-form porphobilinogen and delta-aminolevulinic acid are bound to the resin. After rinsing the column with 3 ml N acetic acid and 1 ml H2O the bound hemprecursors were eluted with 5 ml buffer. Concentration of porphobilinogen and of the pyrrol, synthesized from delta-aminolevulinic acid by Knorr-reaction is measured photometrically at 546 nm after Ehrich-reaction. After a short-time regeneration of columns -- 5 ml buffer, 3 ml N acetic acid -- these columns can be reused at least 20 times.", "contents": "[A new method for the clinical determination of urinary porphobilinogen and delta-aminolevulinic acid]. A new method has been developed for clinical determination of porphobilinogen and delta-aminolevulinic acid in urine. Compared with the method of Mauzerall and Granick, being the most commonly used method for clinical application, there is an essential reduction of work and needed time. During the flow of 0.5 ml urine on a 0.7 cm x 2 cm column of macroporous cation exchange resin in H+-form porphobilinogen and delta-aminolevulinic acid are bound to the resin. After rinsing the column with 3 ml N acetic acid and 1 ml H2O the bound hemprecursors were eluted with 5 ml buffer. Concentration of porphobilinogen and of the pyrrol, synthesized from delta-aminolevulinic acid by Knorr-reaction is measured photometrically at 546 nm after Ehrich-reaction. After a short-time regeneration of columns -- 5 ml buffer, 3 ml N acetic acid -- these columns can be reused at least 20 times."}
{"id": "PMID:14875", "title": "[The effect of anesthesia on the postoperative behavior of liver enzymes and protein fractions].", "content": "Liver tests were performed postoperatively on 25 women with \"healthy\" livers. Patients were divided into 3 groups according to the type of anesthesia used: 1. halothane; 2. neuroleptic; 3. peridural. In all 3 groups the variations in serum proteins and liver enzymes were similar up to the 15th postoperative day. Variations of LDH, AP, LAP, and CHE were within normal range; slight to moderate increases above normal were observed for GPT, GOT, GLDH, and gamma-GT. All 3 groups barely differ with respect to enzyme levels during the postoperative course. We therefore interpret these changes to indicate a reaction of the liver to the stress of operation rather than to the mode of anesthesia.", "contents": "[The effect of anesthesia on the postoperative behavior of liver enzymes and protein fractions]. Liver tests were performed postoperatively on 25 women with \"healthy\" livers. Patients were divided into 3 groups according to the type of anesthesia used: 1. halothane; 2. neuroleptic; 3. peridural. In all 3 groups the variations in serum proteins and liver enzymes were similar up to the 15th postoperative day. Variations of LDH, AP, LAP, and CHE were within normal range; slight to moderate increases above normal were observed for GPT, GOT, GLDH, and gamma-GT. All 3 groups barely differ with respect to enzyme levels during the postoperative course. We therefore interpret these changes to indicate a reaction of the liver to the stress of operation rather than to the mode of anesthesia."}
{"id": "PMID:14890", "title": "Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli: importance of bicarbonate.", "content": "At pH 7.4 and in the presence of NaHCO3, human milk and bovine colostrum inhibited the growth of Escherichia coli O111. Adding sufficient iron to saturate the iron-binding capacity of the lactoferrin present in the milk or colostrum prevented bacteriostasis. At pH 6.8 neither molk nor colostrum inhibited E. coli 0111. Adjusting the pH to 7.4 with NaHCO3 resulted in the development of bacteriostatic activity. Adjusting the pH to 7.4 with NaOH was ineffective. Dialyzed colostrum and milk inhibited bacterial growth at pH 6.8 in the absence of added NaHCO3; addition of citrate or iron abolished bacteriostasis. The chromatographic elution profile of tyrosyl-transfer ribonucleic acid (tRNA) from iron-replete E. coli differs significantly from that of tyrosyl-tRNA from iron-deficient organisms. Examination of the elution profile tyrosyl-tRNA from E. coli 0111 growing in colostrum without added NaHCO3 showed that such bacteria were fully replete in iron. The nature of the elution profile of tyrosyl-tRNA also showed that iron was freely available to the bacteria when citrate was added to dialyzed colostrum but not available in its absence, even at pH 6.8. Results support the idea that the bacteriostatic action of milk and colostrum, due to the combined action of antibody and lactoferrin, depends on the addition of bicarbonate to counteract the iron-mobilizing effect of the citrate normally present in these secretions.", "contents": "Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli: importance of bicarbonate. At pH 7.4 and in the presence of NaHCO3, human milk and bovine colostrum inhibited the growth of Escherichia coli O111. Adding sufficient iron to saturate the iron-binding capacity of the lactoferrin present in the milk or colostrum prevented bacteriostasis. At pH 6.8 neither molk nor colostrum inhibited E. coli 0111. Adjusting the pH to 7.4 with NaHCO3 resulted in the development of bacteriostatic activity. Adjusting the pH to 7.4 with NaOH was ineffective. Dialyzed colostrum and milk inhibited bacterial growth at pH 6.8 in the absence of added NaHCO3; addition of citrate or iron abolished bacteriostasis. The chromatographic elution profile of tyrosyl-transfer ribonucleic acid (tRNA) from iron-replete E. coli differs significantly from that of tyrosyl-tRNA from iron-deficient organisms. Examination of the elution profile tyrosyl-tRNA from E. coli 0111 growing in colostrum without added NaHCO3 showed that such bacteria were fully replete in iron. The nature of the elution profile of tyrosyl-tRNA also showed that iron was freely available to the bacteria when citrate was added to dialyzed colostrum but not available in its absence, even at pH 6.8. Results support the idea that the bacteriostatic action of milk and colostrum, due to the combined action of antibody and lactoferrin, depends on the addition of bicarbonate to counteract the iron-mobilizing effect of the citrate normally present in these secretions."}
{"id": "PMID:14891", "title": "Reproduction of the eosinopenia of acute infection by passive transfer of a material obtained from inflammatory exudate.", "content": "Studies of the eosinopenic effect of acute inflammation were conducted in mice previously rendered eosinophilic with trichinosis. Exudate removed from a pneumococcal abscess contained material (eosinopenic factor [EF]) capable of causing eosinopenia of 4- to 24-h duration when injected intraperitoneally into eosinophilic mice. The material passed through a 0.45-micronm filter, but was retained by a dialysis membrane capable of retaining protein molecules of greater than approximately 30,000 molecular weight. EF was soluble in 7% perchloric acid, was not destroyed by pneumococcal proteolytic enzymes in the presence of Trasylol, but was inactivated by heating to 56 degrees C for 30 min. EF was detectable in the exudate after 10 h and had reached its highest concentration after 20 h. When the effect of EF was expressed as a percent suppression of control eosinophil levels, there was a geometric dose response. Eosinopenia could not be ascribed to steroids present in the preparation, and the EF was effective in adrenalectomized animals. Eosinopenia was not induced by transfer of similarly treated heat-killed pneumococci, pneumococcal culture filtrate, or normal serum. The eosinopenia of acute infection may be the direct effect of a substance present at the site of acute inflammation.", "contents": "Reproduction of the eosinopenia of acute infection by passive transfer of a material obtained from inflammatory exudate. Studies of the eosinopenic effect of acute inflammation were conducted in mice previously rendered eosinophilic with trichinosis. Exudate removed from a pneumococcal abscess contained material (eosinopenic factor [EF]) capable of causing eosinopenia of 4- to 24-h duration when injected intraperitoneally into eosinophilic mice. The material passed through a 0.45-micronm filter, but was retained by a dialysis membrane capable of retaining protein molecules of greater than approximately 30,000 molecular weight. EF was soluble in 7% perchloric acid, was not destroyed by pneumococcal proteolytic enzymes in the presence of Trasylol, but was inactivated by heating to 56 degrees C for 30 min. EF was detectable in the exudate after 10 h and had reached its highest concentration after 20 h. When the effect of EF was expressed as a percent suppression of control eosinophil levels, there was a geometric dose response. Eosinopenia could not be ascribed to steroids present in the preparation, and the EF was effective in adrenalectomized animals. Eosinopenia was not induced by transfer of similarly treated heat-killed pneumococci, pneumococcal culture filtrate, or normal serum. The eosinopenia of acute infection may be the direct effect of a substance present at the site of acute inflammation."}
{"id": "PMID:14892", "title": "Magnesium-dependent adenosine triphosphatase as a marker enzyme for the plasma membrane of human polymorphonuclear leukocytes.", "content": "The adenosine triphosphatase (ATPase) activities of human polymorphonuclear leukocytes (PMNL) were studied with an assay that monitored the release of 32P-labeled inorganic pyrophosphate (32P1) from gamma-[32P]adenosine 5'-triphosphate (ATP). In cell homogenates, (Na+ + K+)-sensitive, ouabain-inhibitable ATPase comprised an insignificant fraction of the total ATPase activity. Additions of p-nitrophenyl phosphate and beta-glycerophosphate (substrates for nonspecific acid and alkaline phosphatases) and of tartrate (inhibitor of acid phosphatase) gave no indication of inhibition. This suggested that the assay was relatively specific for ATP hydrolysis. The activity was found to have a pH optimum of 8.7 and a Km for ATP of 0.6 mM. There was an absolute requirement for Mg2+, with other divalent cations substituting less efficiently. When the Mg2+-dependent ATPase activity of intact cells was compared with that in homogenized cells, no significant difference was observed. The activity in intact cells was linear with respect to incubation time up to at least l0 min. Trypan blue staining and lactate dehydrogenase assays revealed that greater than 92% of the PMNL remained intact and viable during the assay. No soluble ATPase was released from the cells under assay conditions. In following the distribution of gamma[32P]ATP and 32P2 counts became cell associated. Since the experimental evidence supports the observation that PMNL remain intact and viable and that ATP does not penetrate the cell under assay conditions, it is proposed that greater than 90% of the Mg2+-dependent ATPase of the human PMNL is associated with a plasma membrnae enzyme. This would qualify the enzyme for the role of a plasma membrane marker for future fractionation and isolation attempts.", "contents": "Magnesium-dependent adenosine triphosphatase as a marker enzyme for the plasma membrane of human polymorphonuclear leukocytes. The adenosine triphosphatase (ATPase) activities of human polymorphonuclear leukocytes (PMNL) were studied with an assay that monitored the release of 32P-labeled inorganic pyrophosphate (32P1) from gamma-[32P]adenosine 5'-triphosphate (ATP). In cell homogenates, (Na+ + K+)-sensitive, ouabain-inhibitable ATPase comprised an insignificant fraction of the total ATPase activity. Additions of p-nitrophenyl phosphate and beta-glycerophosphate (substrates for nonspecific acid and alkaline phosphatases) and of tartrate (inhibitor of acid phosphatase) gave no indication of inhibition. This suggested that the assay was relatively specific for ATP hydrolysis. The activity was found to have a pH optimum of 8.7 and a Km for ATP of 0.6 mM. There was an absolute requirement for Mg2+, with other divalent cations substituting less efficiently. When the Mg2+-dependent ATPase activity of intact cells was compared with that in homogenized cells, no significant difference was observed. The activity in intact cells was linear with respect to incubation time up to at least l0 min. Trypan blue staining and lactate dehydrogenase assays revealed that greater than 92% of the PMNL remained intact and viable during the assay. No soluble ATPase was released from the cells under assay conditions. In following the distribution of gamma[32P]ATP and 32P2 counts became cell associated. Since the experimental evidence supports the observation that PMNL remain intact and viable and that ATP does not penetrate the cell under assay conditions, it is proposed that greater than 90% of the Mg2+-dependent ATPase of the human PMNL is associated with a plasma membrnae enzyme. This would qualify the enzyme for the role of a plasma membrane marker for future fractionation and isolation attempts."}
{"id": "PMID:14893", "title": "Levan and levansucrase of Actinomyces viscosus.", "content": "A levansucrase was demonstrated in the growth medium and in association with the cell surface of Actinomyces viscosus. The amount of enzyme produced relative to cell density is not significantly affected by the growth conditions. Sugar alcohols inhibit growth of the cells. The levansucrase hydrolyzes sucrose to produce free glucose and levan; some free fructose is also formed. There is no requirement for cofactors. The Km for sucrose is 12 mM. A variety of heavy metal ions and two disaccharides, lactose and cellobiose, inhibit the enzyme. The levansucrase was purified to homogeneity and has a specific activity of 90 micronmol of glucose release per min per mg. The enzyme has a molecular weight of 220,000 and is composed of subunits of molecular weight 80,000. The levan product contains both beta(2 leads to 1) and beta(2 leads to 6) linkages. The enzyme remains tightly bound to the levan product, resulting in the formation of high-molecular-weight polymer on the order of 10(8) daltons. The possible role of the levan and levansucrase of A. viscosus in the pathogenesis of periodontal disease is discussed.", "contents": "Levan and levansucrase of Actinomyces viscosus. A levansucrase was demonstrated in the growth medium and in association with the cell surface of Actinomyces viscosus. The amount of enzyme produced relative to cell density is not significantly affected by the growth conditions. Sugar alcohols inhibit growth of the cells. The levansucrase hydrolyzes sucrose to produce free glucose and levan; some free fructose is also formed. There is no requirement for cofactors. The Km for sucrose is 12 mM. A variety of heavy metal ions and two disaccharides, lactose and cellobiose, inhibit the enzyme. The levansucrase was purified to homogeneity and has a specific activity of 90 micronmol of glucose release per min per mg. The enzyme has a molecular weight of 220,000 and is composed of subunits of molecular weight 80,000. The levan product contains both beta(2 leads to 1) and beta(2 leads to 6) linkages. The enzyme remains tightly bound to the levan product, resulting in the formation of high-molecular-weight polymer on the order of 10(8) daltons. The possible role of the levan and levansucrase of A. viscosus in the pathogenesis of periodontal disease is discussed."}
{"id": "PMID:14896", "title": "Tumorigenicity of human hematopoietic cell lines in athymic nude mice.", "content": "Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi-solid medium in vitro. Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein-Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of come of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.", "contents": "Tumorigenicity of human hematopoietic cell lines in athymic nude mice. Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi-solid medium in vitro. Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein-Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of come of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines."}
{"id": "PMID:14897", "title": "Studies on Epstein-Barr virus-related antigens. II. Biochemical properties of soluble antigen in Raji Burkitt lymphoma cells.", "content": "Biochemical properties of Epstein-Barr virus (EBV)-related soluble antigen in non-producer Raji Burkitt lymphoblastoid cells, assayed by the indirect single radial immunodiffusion (ISRD) test, were investigated. The soluble ISRD antigen retained activity even after exposure to a temperature of 80 degrees C. The antigen was precipitated in 40% saturated ammonium sulfate and ISRD activity was recovered from the precipitate when reconstituted into a solution. Isoelectric focusing and crossed immunoelectrophoretic analyses revealed that the esoelectric point of the ISRD antigen is pH 4.8 with an electrophoretic mobility similar to that of serum alpha-globulin. With Sephadex G-200 or Sepharose 6B gel filtration, ISRD activity was obtained as a single peak which corresponded to the activity absorbing anti-complement immunofluorescence. The molecular weight of the present EBV-related soluble antigen was estimated to be 220,000-2408000 daltons.", "contents": "Studies on Epstein-Barr virus-related antigens. II. Biochemical properties of soluble antigen in Raji Burkitt lymphoma cells. Biochemical properties of Epstein-Barr virus (EBV)-related soluble antigen in non-producer Raji Burkitt lymphoblastoid cells, assayed by the indirect single radial immunodiffusion (ISRD) test, were investigated. The soluble ISRD antigen retained activity even after exposure to a temperature of 80 degrees C. The antigen was precipitated in 40% saturated ammonium sulfate and ISRD activity was recovered from the precipitate when reconstituted into a solution. Isoelectric focusing and crossed immunoelectrophoretic analyses revealed that the esoelectric point of the ISRD antigen is pH 4.8 with an electrophoretic mobility similar to that of serum alpha-globulin. With Sephadex G-200 or Sepharose 6B gel filtration, ISRD activity was obtained as a single peak which corresponded to the activity absorbing anti-complement immunofluorescence. The molecular weight of the present EBV-related soluble antigen was estimated to be 220,000-2408000 daltons."}
{"id": "PMID:14898", "title": "Purification of several proteolytic enzymes by tosyl- and carbobenzoxy-triethylene-tetramine-sepharoses.", "content": "Tosyl-triethylenetetramine-Sepharose (Tos-T-Sepharose) and carbenzoxytriethylenetetramine-Sepharose (Z-T-Sepharose) were found to be adsorbents utilizable in the purification of several microbial and animal proteases. The former Sepharose derivative adsorbed alpha-chymotrypsin, trypsin, subtilisin, thermolysin and neutral subtilopeptidase at neutral pH range, and acid proteases such as pepsin and Rhizopus niveus protease at pH 3.5-6.5. alpha-Chymotrypsin and trypsin were eluted with 0.1 N acetic acid and Rhizopus protease with 0.5 N acetic acid, thermolysin with 1 M guanidine-HCl or 33% ethyleneglycol, whilst pepsin was recovered by elution with 2 M guanidine-HCl at pH 3.5. The binding of neutral subtilopeptidase and subtilisin to this adsorbent was comparatively weak and both the enzymes were recovered by elution with 0.5 M NaCl at neutral pH. On the other hand, Z-T-Sepharose was found to bind tightly to these proteolytic enzymes except neutral subtilopeptidase. Trypsin and alpha-chymotrypsin were released from the adsorbent column with 1 M p-toluenesulfonate, and subtilisin with 1 M guanidine-HCl or 33% ethyleneglycol at neutral pH region. By these chromatographic procedures, the specific activities of these proteolytic enzymes increased effectively. Comparison of the binding abilities of acetyl-, benzoyl-, tosyl- and carbobenzoxy-T-Sepharoses to these enzymes suggests that hydrophobicity of tosyl and carbobenzoxy groups plays an important role in the enzyme-adsorbent interaction.", "contents": "Purification of several proteolytic enzymes by tosyl- and carbobenzoxy-triethylene-tetramine-sepharoses. Tosyl-triethylenetetramine-Sepharose (Tos-T-Sepharose) and carbenzoxytriethylenetetramine-Sepharose (Z-T-Sepharose) were found to be adsorbents utilizable in the purification of several microbial and animal proteases. The former Sepharose derivative adsorbed alpha-chymotrypsin, trypsin, subtilisin, thermolysin and neutral subtilopeptidase at neutral pH range, and acid proteases such as pepsin and Rhizopus niveus protease at pH 3.5-6.5. alpha-Chymotrypsin and trypsin were eluted with 0.1 N acetic acid and Rhizopus protease with 0.5 N acetic acid, thermolysin with 1 M guanidine-HCl or 33% ethyleneglycol, whilst pepsin was recovered by elution with 2 M guanidine-HCl at pH 3.5. The binding of neutral subtilopeptidase and subtilisin to this adsorbent was comparatively weak and both the enzymes were recovered by elution with 0.5 M NaCl at neutral pH. On the other hand, Z-T-Sepharose was found to bind tightly to these proteolytic enzymes except neutral subtilopeptidase. Trypsin and alpha-chymotrypsin were released from the adsorbent column with 1 M p-toluenesulfonate, and subtilisin with 1 M guanidine-HCl or 33% ethyleneglycol at neutral pH region. By these chromatographic procedures, the specific activities of these proteolytic enzymes increased effectively. Comparison of the binding abilities of acetyl-, benzoyl-, tosyl- and carbobenzoxy-T-Sepharoses to these enzymes suggests that hydrophobicity of tosyl and carbobenzoxy groups plays an important role in the enzyme-adsorbent interaction."}
{"id": "PMID:14899", "title": "The acylation of bovine serum albumin with diacetylcycloserine.", "content": "The reaction of the amino groups of bovine serum albumin (BSA) with diacetylcycloserine (I) at pH 7.2-9.0 proceeded with both acylation by the diacetyl-beta-aminooxy-D-alanyl (DAA) group and acetylation. The number of DAA groups was determined by their conversion to cycloserine (III) which can be accurately measured in micromolar amounts. The method was developed using the model compound diacetyl-beta-aminooxy-D-alanine butyl amide (II) which was converted to beta-aminooxy-D-alanine butyl amide (IV) by methanolysis and then to cycloserine by basic ring-closure of IV. Calculations using results obtained by this method combined with the experimentally determined number of free amino groups in the modified BSA indicated that the reaction of excess I with BSA effected the acetylation of about 35 and the acylation with DAA groups of about 22 of the 59 amino groups. These findings were supported by experiments demonstrating that the amount of acetic acid formed by hydrolysis of the modified BSA was approximately that predicted from the results of the cycloserine analyses.", "contents": "The acylation of bovine serum albumin with diacetylcycloserine. The reaction of the amino groups of bovine serum albumin (BSA) with diacetylcycloserine (I) at pH 7.2-9.0 proceeded with both acylation by the diacetyl-beta-aminooxy-D-alanyl (DAA) group and acetylation. The number of DAA groups was determined by their conversion to cycloserine (III) which can be accurately measured in micromolar amounts. The method was developed using the model compound diacetyl-beta-aminooxy-D-alanine butyl amide (II) which was converted to beta-aminooxy-D-alanine butyl amide (IV) by methanolysis and then to cycloserine by basic ring-closure of IV. Calculations using results obtained by this method combined with the experimentally determined number of free amino groups in the modified BSA indicated that the reaction of excess I with BSA effected the acetylation of about 35 and the acylation with DAA groups of about 22 of the 59 amino groups. These findings were supported by experiments demonstrating that the amount of acetic acid formed by hydrolysis of the modified BSA was approximately that predicted from the results of the cycloserine analyses."}
{"id": "PMID:14900", "title": "Iodinated radiological contrast media as radiosensitizers.", "content": "This paper describes the radiosensitizing effects of diatrizoic (DA) and iothalamic (ITA) acids and of iodipamide (IP) on the survival of E coli B/r irradiated with X-rays and with high-intensity electron pulses. All compounds at concentrations between 10 and 50 mM display a strong sensitizing effect in the presence of oxygen (DMF between 0-1 and 0-3) and are much less effective in nitrogen. In N2O the degree of sensitization is intermediate between oxygen and nitrogen. The situation is the same at pH 7 or 5-6. Solutions of DA, ITA and IP irradiated at pH lower than 6 become highly toxic to bacteria added after irradiation, for several hours after X-irradiation or several minutes after pulsed irradiation. The maximum toxic effect occurs with 2 krad of X-ray and with 6-8 krad of electrons. Oxygen must be present in order to observe the bactericidal activity. This is not affected by scavenging hydrated electrons with nitrate, but is completely cancelled by scavenging OH radicals with formate. It is also cancelled by adding thiosulphate to the irradiated solutions immediately before the bacteria. In the presence of nutrient broth, the radiosensitizing effect is absent after irradiation with pulsed electrons; whereas after X-irradiation it is reduced when the concentration of sensitizers is 50 mM. The experimental data appear to be compatible with a mechanism operated by short and long-lived transients resulting from the radiolysis of iodinated contrast media.", "contents": "Iodinated radiological contrast media as radiosensitizers. This paper describes the radiosensitizing effects of diatrizoic (DA) and iothalamic (ITA) acids and of iodipamide (IP) on the survival of E coli B/r irradiated with X-rays and with high-intensity electron pulses. All compounds at concentrations between 10 and 50 mM display a strong sensitizing effect in the presence of oxygen (DMF between 0-1 and 0-3) and are much less effective in nitrogen. In N2O the degree of sensitization is intermediate between oxygen and nitrogen. The situation is the same at pH 7 or 5-6. Solutions of DA, ITA and IP irradiated at pH lower than 6 become highly toxic to bacteria added after irradiation, for several hours after X-irradiation or several minutes after pulsed irradiation. The maximum toxic effect occurs with 2 krad of X-ray and with 6-8 krad of electrons. Oxygen must be present in order to observe the bactericidal activity. This is not affected by scavenging hydrated electrons with nitrate, but is completely cancelled by scavenging OH radicals with formate. It is also cancelled by adding thiosulphate to the irradiated solutions immediately before the bacteria. In the presence of nutrient broth, the radiosensitizing effect is absent after irradiation with pulsed electrons; whereas after X-irradiation it is reduced when the concentration of sensitizers is 50 mM. The experimental data appear to be compatible with a mechanism operated by short and long-lived transients resulting from the radiolysis of iodinated contrast media."}
{"id": "PMID:14906", "title": "The activity and distribution of gamma-glutamyl transpeptidase (y-GT) in human foetal organs.", "content": "The activity and distribution of y-GT was investigated in a number of organs from human foetuses aged from 14 to 24 weeks post menstruationem. Over this period, enzyme activity increased in the kidney, pancreas and thymus, but decreased in the small intestine. No trend could be established for the liver, although activity was high. In the lung, spleen, brain and adrenals, y-GT was either detectable at very low levels or could not be demonstrated. The possible relationship between y-GT activity in some human tumours and the enzyme level in the corresponding foetal organs is discussed.", "contents": "The activity and distribution of gamma-glutamyl transpeptidase (y-GT) in human foetal organs. The activity and distribution of y-GT was investigated in a number of organs from human foetuses aged from 14 to 24 weeks post menstruationem. Over this period, enzyme activity increased in the kidney, pancreas and thymus, but decreased in the small intestine. No trend could be established for the liver, although activity was high. In the lung, spleen, brain and adrenals, y-GT was either detectable at very low levels or could not be demonstrated. The possible relationship between y-GT activity in some human tumours and the enzyme level in the corresponding foetal organs is discussed."}
{"id": "PMID:14904", "title": "Subcellular distribution of pyridoxal kinase in ox retina.", "content": "PL kinase activity has been determined in primary and secondary subcellular fractions of ox retina. Enzymic activity is predominantly located in the soluble fraction (S3). About 65% of the recovered PL kinase activity of crude mitochondria is released from synaptosomal fraction after hypoosmotic treatment. PL kinase activity in supernatant fraction (S3) does not exceed the enzyme activity measured in the homogenate, excluding the presence of a particulate-bound inhibitor to PL kinase in the homogenate. The possible physiological significance of PL kinase cellular compartmentation has been considered.", "contents": "Subcellular distribution of pyridoxal kinase in ox retina. PL kinase activity has been determined in primary and secondary subcellular fractions of ox retina. Enzymic activity is predominantly located in the soluble fraction (S3). About 65% of the recovered PL kinase activity of crude mitochondria is released from synaptosomal fraction after hypoosmotic treatment. PL kinase activity in supernatant fraction (S3) does not exceed the enzyme activity measured in the homogenate, excluding the presence of a particulate-bound inhibitor to PL kinase in the homogenate. The possible physiological significance of PL kinase cellular compartmentation has been considered."}
{"id": "PMID:14919", "title": "Purification and properties of glutamate synthase from Thiobacillus thioparus.", "content": "Glutamate synthase was purified about 250-fold from Thiobacillus thioparus and was characterized. The molecular weight was estimated as 280,000 g/mol. The enzyme showed absorption maxima at 280, 380, and 450 nm and was inhibited by Atebrin, suggesting that T. thioparus glutamate synthase is a flavoprotein. The enzyme activity was also inhibited by iron chelators and thiolbinding agents. The enzyme was specific for reduced nicotinamide adenine dinucleotide phosphate (NADPH) and alpha-ketoglutarate, but L-glutamine was partially replaced by ammonia as the amino donor. The Km values of glutamate synthase for NADPH, alpha-ketoglutarate, and glutamine were 3.0 muM, 50 muM, and 1.1 mM, respectively. The enzyme had a pH optimum between 7.3 and 7.8. Glutamate synthase from T. thioparus was relatively insensitive to feedback inhibition by single amino acids but was sensitive to the combined effects of several amino acids. Enzymes involved in glutamate synthesis in T. thioparus were studied. Glutamine synthetase and glutamate synthase, as well as two glutamate dehydrogenases (NADH and NADPH dependent), were present in this organism. This levels of glutamate synthase and glutamate dehydrogenase were similar in T. thioparus grown on 0.7 or 7.0 mM ammonium sulfate. The sum of the activities of both glutamate dehydrogenases was only 1/25 of that of glutamate synthase under the assay conditions. It was concluded that the glutamine pathway is important for ammonia assimilation in this autotrophic bacterium.", "contents": "Purification and properties of glutamate synthase from Thiobacillus thioparus. Glutamate synthase was purified about 250-fold from Thiobacillus thioparus and was characterized. The molecular weight was estimated as 280,000 g/mol. The enzyme showed absorption maxima at 280, 380, and 450 nm and was inhibited by Atebrin, suggesting that T. thioparus glutamate synthase is a flavoprotein. The enzyme activity was also inhibited by iron chelators and thiolbinding agents. The enzyme was specific for reduced nicotinamide adenine dinucleotide phosphate (NADPH) and alpha-ketoglutarate, but L-glutamine was partially replaced by ammonia as the amino donor. The Km values of glutamate synthase for NADPH, alpha-ketoglutarate, and glutamine were 3.0 muM, 50 muM, and 1.1 mM, respectively. The enzyme had a pH optimum between 7.3 and 7.8. Glutamate synthase from T. thioparus was relatively insensitive to feedback inhibition by single amino acids but was sensitive to the combined effects of several amino acids. Enzymes involved in glutamate synthesis in T. thioparus were studied. Glutamine synthetase and glutamate synthase, as well as two glutamate dehydrogenases (NADH and NADPH dependent), were present in this organism. This levels of glutamate synthase and glutamate dehydrogenase were similar in T. thioparus grown on 0.7 or 7.0 mM ammonium sulfate. The sum of the activities of both glutamate dehydrogenases was only 1/25 of that of glutamate synthase under the assay conditions. It was concluded that the glutamine pathway is important for ammonia assimilation in this autotrophic bacterium."}
{"id": "PMID:14920", "title": "Pyrrolidone carboxylyl peptidase in Streptococcus cremoris: dependence on an interaction with membrane components.", "content": "A study of the distribution of pyrrolidone carboxylyl peptidase (PCP) activity among cell fractions of Streptococcus cremoris HP revealed that this enzyme is associated with a particulate fraction, which mainly consists of membrane material. This location could only be established using a gentle nonmechanical method for the disruption of spheroplasts under the conditions of which intracellular marker enzymes are released. The effect of monovalent anions and treatments, which do not destroy covalent binding, suggests an association of the enzyme with surrounding structures determined by both hydrophobic and electrostatic interactions. The activity of PCP associated with cells harvested from different growth phases and in the solubilized state was studied as a function of the temperature in the absence and in the presence of the membrane-interfering agent n-butanol. A decrease in the apparent activation energy, inherent to the solubilized enzyme, is induced in situ at a lower transition temperature. Only with logarithmic-phase cells is this transition followed (mid-logarithmic cells) or accompanied (late logarithmic cells) by a secondary decrease in the energy of activation. n-Butanol appeared to decrease the lower transition temperature of the enzyme activity in situ, and additionally it exerted an effect on the manifestation of the secondary transition. Thecorganization of membrane components, mainly the lipids.", "contents": "Pyrrolidone carboxylyl peptidase in Streptococcus cremoris: dependence on an interaction with membrane components. A study of the distribution of pyrrolidone carboxylyl peptidase (PCP) activity among cell fractions of Streptococcus cremoris HP revealed that this enzyme is associated with a particulate fraction, which mainly consists of membrane material. This location could only be established using a gentle nonmechanical method for the disruption of spheroplasts under the conditions of which intracellular marker enzymes are released. The effect of monovalent anions and treatments, which do not destroy covalent binding, suggests an association of the enzyme with surrounding structures determined by both hydrophobic and electrostatic interactions. The activity of PCP associated with cells harvested from different growth phases and in the solubilized state was studied as a function of the temperature in the absence and in the presence of the membrane-interfering agent n-butanol. A decrease in the apparent activation energy, inherent to the solubilized enzyme, is induced in situ at a lower transition temperature. Only with logarithmic-phase cells is this transition followed (mid-logarithmic cells) or accompanied (late logarithmic cells) by a secondary decrease in the energy of activation. n-Butanol appeared to decrease the lower transition temperature of the enzyme activity in situ, and additionally it exerted an effect on the manifestation of the secondary transition. Thecorganization of membrane components, mainly the lipids."}
{"id": "PMID:14921", "title": "Partial purification of the Escherichia coli K-12 mec+ deoxyribonucleic acid-cytosine methylase: in vitro methylation completely protects bacteriophage lambda deoxyribonucleic acid against cleavage by R-EcoRII.", "content": "A procedure is described for the partial purification of the deoxyribonucleic acid (DNA)-cytosine methylases controlled by the RII plasmid and by the Escherichia coli mec+ gene. The two enzymes exhibit similar but distinct chromatographic behavior on diethylaminoethyl-cellulose and phosphocellulose. Preliminary studies on the two methylases indicate that they are indistinguishable with respect to their Km for S-adenosylmethionine and their pH (in tris (hydroxymethyl)aminomethane buffer) and NaCl concentration optima. In vitro methylation of various phage lambda DNA substrates by the mec'r RII enzyme modifies the DNA to a form that is completely resistant to double-stranded cleavage by the RII restriction endonuclease (R-EcoRII). These results are consistent with our earlier proposal that the mec8ethylase recognizes RII host specificity sites.", "contents": "Partial purification of the Escherichia coli K-12 mec+ deoxyribonucleic acid-cytosine methylase: in vitro methylation completely protects bacteriophage lambda deoxyribonucleic acid against cleavage by R-EcoRII. A procedure is described for the partial purification of the deoxyribonucleic acid (DNA)-cytosine methylases controlled by the RII plasmid and by the Escherichia coli mec+ gene. The two enzymes exhibit similar but distinct chromatographic behavior on diethylaminoethyl-cellulose and phosphocellulose. Preliminary studies on the two methylases indicate that they are indistinguishable with respect to their Km for S-adenosylmethionine and their pH (in tris (hydroxymethyl)aminomethane buffer) and NaCl concentration optima. In vitro methylation of various phage lambda DNA substrates by the mec'r RII enzyme modifies the DNA to a form that is completely resistant to double-stranded cleavage by the RII restriction endonuclease (R-EcoRII). These results are consistent with our earlier proposal that the mec8ethylase recognizes RII host specificity sites."}
{"id": "PMID:14922", "title": "Sterol 24(28) methylene reductase in Saccharomyces cerevisiae.", "content": "Optimal conditions for the 24(28)methylene reductase were obtained. The enzyme assay provided for unusually high activity; the Km was determined to be 10.8 mum. The enzyme activity was increased in cells grown with ethanol as the substrate.", "contents": "Sterol 24(28) methylene reductase in Saccharomyces cerevisiae. Optimal conditions for the 24(28)methylene reductase were obtained. The enzyme assay provided for unusually high activity; the Km was determined to be 10.8 mum. The enzyme activity was increased in cells grown with ethanol as the substrate."}
{"id": "PMID:14923", "title": "Ornithine transcarbamylase from Salmonella typhimurium: purification, subunit composition, kinetic analysis, and immunological cross-reactivity.", "content": "Ornithine transcarbamylase (OTCase) was purified to hemogeneity from a derepressed strain of Salmonella typhimurium. The optimal pH for enzyme activity is 8.0. The molecular weight of the enzyme was calculated to be 116,000, based on measurements of the sedimentation coefficient by sucrose gradient ultracentrifugation and the Stokes radius by gel filtration. Polyacrylamide gel electrophoresis of cross-linked OTCase in the presence of sodium dodecyl sulfate showed that the enzyme is composed of three identical subunits. The molecular weight of the monomer was determined to be 39,000. Steady-state kinetics indicate that the reaction mechanism is sequential. The limiting Michealis constants for carbamylphosphate and ornithine were determined to be 0.06 and 0.2 mM, respectively. The dissociation constant for carbamylphosphate was 0.02 mM. Product and dead-end inhibition patterns are consistent with an ordered Bi Bi mechanism, in which carbamylphosphate is the first substrate added and phosphate is the last product released. OTCase activity was inhibited by arginine, but relatively high concentrations were required for significant inhibition. The inhibition by arginine might be physiologically significant in the regulation of carbamlphosphate utilization; a single carbamylphosphate synthetase is responsible for the synthesis of carbamylphosphate for both arginine and pyrimidines in S. typhimurium and the inhibition by argine might serve to divert carbamlphosphate to the synthesis of pyrimidines when arginine is present at high concentrations. The crossreaction of OTCases from different microorganisms with purified antibodies raised against the homogeneous OTCase from S. typhimurium was investigated. The results of immunotitration and immunodiffusion experiments revealed a high degree of identity between the enzymes form S. typhimurium and Esherichia coli B and W. In these three cases, a single gen (argl) encodes OTCase. Wild-type E. coli K-12 and strain 3000 X 111, which carry two OTCase genes (argI, argF), also revealed similar cross-reactivity, supporting the hypothesis that argF is the product of a relatively recent duplication. The activity of OTCase from Bacillus subtilis was partially inhibited by antibodies against the enzyme from S. typhimurium, indicating unusual conservation of primary structure among widely different taxonomic groups. OTCase from Saccharomyces cerevisiae, whose molecular weight and primary structure are similar to those of the enzyme from S. typhimurium, was without detectable cross-reactivity.", "contents": "Ornithine transcarbamylase from Salmonella typhimurium: purification, subunit composition, kinetic analysis, and immunological cross-reactivity. Ornithine transcarbamylase (OTCase) was purified to hemogeneity from a derepressed strain of Salmonella typhimurium. The optimal pH for enzyme activity is 8.0. The molecular weight of the enzyme was calculated to be 116,000, based on measurements of the sedimentation coefficient by sucrose gradient ultracentrifugation and the Stokes radius by gel filtration. Polyacrylamide gel electrophoresis of cross-linked OTCase in the presence of sodium dodecyl sulfate showed that the enzyme is composed of three identical subunits. The molecular weight of the monomer was determined to be 39,000. Steady-state kinetics indicate that the reaction mechanism is sequential. The limiting Michealis constants for carbamylphosphate and ornithine were determined to be 0.06 and 0.2 mM, respectively. The dissociation constant for carbamylphosphate was 0.02 mM. Product and dead-end inhibition patterns are consistent with an ordered Bi Bi mechanism, in which carbamylphosphate is the first substrate added and phosphate is the last product released. OTCase activity was inhibited by arginine, but relatively high concentrations were required for significant inhibition. The inhibition by arginine might be physiologically significant in the regulation of carbamlphosphate utilization; a single carbamylphosphate synthetase is responsible for the synthesis of carbamylphosphate for both arginine and pyrimidines in S. typhimurium and the inhibition by argine might serve to divert carbamlphosphate to the synthesis of pyrimidines when arginine is present at high concentrations. The crossreaction of OTCases from different microorganisms with purified antibodies raised against the homogeneous OTCase from S. typhimurium was investigated. The results of immunotitration and immunodiffusion experiments revealed a high degree of identity between the enzymes form S. typhimurium and Esherichia coli B and W. In these three cases, a single gen (argl) encodes OTCase. Wild-type E. coli K-12 and strain 3000 X 111, which carry two OTCase genes (argI, argF), also revealed similar cross-reactivity, supporting the hypothesis that argF is the product of a relatively recent duplication. The activity of OTCase from Bacillus subtilis was partially inhibited by antibodies against the enzyme from S. typhimurium, indicating unusual conservation of primary structure among widely different taxonomic groups. OTCase from Saccharomyces cerevisiae, whose molecular weight and primary structure are similar to those of the enzyme from S. typhimurium, was without detectable cross-reactivity."}
{"id": "PMID:14924", "title": "Properties of an inducible extracellular neuraminidase from an Arthrobacter isolate.", "content": "The elective isolation of a soil microorganism, tentatively assigned to the genus Arthrobacter, which produced an extracellular neuraminidase is described. The secretion of neuraminidase from washed cells in minimal medium required the presence of sialo-containing glycoproteins, whereas free N-acetyl-neuraminic asid of N-acetylmannosamine were poor inducers. No enzyme could be dected in the induction fitrated of cells, in the absence of inducer or in the culture filtrate of cells grown in a complete medium. The routine enzyme inducer was a hot-water extract of \"edible bird's nest.\" Mild acid treatment (0.05 N H2SO4) of this extract increased enzyme activity two--to threefold and the specific activity about eightfold. Neuraminidase induction with acid-treated bird's nest was manifested at a linear rate for 6 h without increase in cell number. No other anticipated glycohydrolase or protease activities were foud. The amount of enzyme located within the cells was barely detectable as compared to that found in the induction filtrate. Experiments with chloramphenicol or chlortetracycline indicate that de novo protein synthesis was required for neuraminidase production and that this exoenzyme was not released from a preformed pool. Neuraminidase from this source has an apparent molecular weight of 87,000, a pH optimum of 5 to 6, and an apparent Km of 2.08 mg/ml for collocalia mucoid and 3.3 X 10(-3) M for N-acetylneuraminlactose and is insensitive both to Ca2+ ions and ethylenediaminetetraacetic acid. Preliminary studies indicate that the enzyme can hydrolyze alpha-2,3-, alpha-2,6-, or alph-2-8-N-acetylneuraminylglycosidic linkages. From total activity data and purification criteria, it would appear that this isolate can produce about 5 mg of enzyme per liter of induction medium.", "contents": "Properties of an inducible extracellular neuraminidase from an Arthrobacter isolate. The elective isolation of a soil microorganism, tentatively assigned to the genus Arthrobacter, which produced an extracellular neuraminidase is described. The secretion of neuraminidase from washed cells in minimal medium required the presence of sialo-containing glycoproteins, whereas free N-acetyl-neuraminic asid of N-acetylmannosamine were poor inducers. No enzyme could be dected in the induction fitrated of cells, in the absence of inducer or in the culture filtrate of cells grown in a complete medium. The routine enzyme inducer was a hot-water extract of \"edible bird's nest.\" Mild acid treatment (0.05 N H2SO4) of this extract increased enzyme activity two--to threefold and the specific activity about eightfold. Neuraminidase induction with acid-treated bird's nest was manifested at a linear rate for 6 h without increase in cell number. No other anticipated glycohydrolase or protease activities were foud. The amount of enzyme located within the cells was barely detectable as compared to that found in the induction filtrate. Experiments with chloramphenicol or chlortetracycline indicate that de novo protein synthesis was required for neuraminidase production and that this exoenzyme was not released from a preformed pool. Neuraminidase from this source has an apparent molecular weight of 87,000, a pH optimum of 5 to 6, and an apparent Km of 2.08 mg/ml for collocalia mucoid and 3.3 X 10(-3) M for N-acetylneuraminlactose and is insensitive both to Ca2+ ions and ethylenediaminetetraacetic acid. Preliminary studies indicate that the enzyme can hydrolyze alpha-2,3-, alpha-2,6-, or alph-2-8-N-acetylneuraminylglycosidic linkages. From total activity data and purification criteria, it would appear that this isolate can produce about 5 mg of enzyme per liter of induction medium."}
{"id": "PMID:14925", "title": "Motility of Mycoplasma pneumoniae.", "content": "Cell of Mycoplasma pneumoniae FH gliding on a glass surface in liquid medium were examined by microscopic observation and quantitatively by microcinematography (30 frames per min). Comparisons were made only within the individual experiments. The cells moved in an irregular pattern with numerous narrow bends and circles. They never changed their leading end. The average speed (without pauses) was relatively constant between o.2 and 0.5 mum/s. The maximum speed was about 1.5 to 2.0 mum/s. The movements were interrupted by resting periods  of different lengths and frequency. Temperature, viscosity, pH, and the presence of yeast extract in the medium influenced the motility significantly; changes in glucose, calcium ions, and serum content were less effective. The movements were affected by iodoacetate, p-mercuribenzoate, and mitomycin C at inhibitory or subinhibitory concentrations. Sodium fluoride, sodium cyanide, dinitrophenol, chloramphenicol, puromycin, cholchicin, and cytochalasin B at minimal inhibitory concentrations did not affect motility. The movements were effectively inhibited by anti-M. pneumoniae antiserum. Studies with absorbed antiserum suggested that the surface  components involved in motility are heat labile. The gliding of M. pneumoniae cells required an intact energy metabolism and the proteins involved seemed to have a low turnover.", "contents": "Motility of Mycoplasma pneumoniae. Cell of Mycoplasma pneumoniae FH gliding on a glass surface in liquid medium were examined by microscopic observation and quantitatively by microcinematography (30 frames per min). Comparisons were made only within the individual experiments. The cells moved in an irregular pattern with numerous narrow bends and circles. They never changed their leading end. The average speed (without pauses) was relatively constant between o.2 and 0.5 mum/s. The maximum speed was about 1.5 to 2.0 mum/s. The movements were interrupted by resting periods  of different lengths and frequency. Temperature, viscosity, pH, and the presence of yeast extract in the medium influenced the motility significantly; changes in glucose, calcium ions, and serum content were less effective. The movements were affected by iodoacetate, p-mercuribenzoate, and mitomycin C at inhibitory or subinhibitory concentrations. Sodium fluoride, sodium cyanide, dinitrophenol, chloramphenicol, puromycin, cholchicin, and cytochalasin B at minimal inhibitory concentrations did not affect motility. The movements were effectively inhibited by anti-M. pneumoniae antiserum. Studies with absorbed antiserum suggested that the surface  components involved in motility are heat labile. The gliding of M. pneumoniae cells required an intact energy metabolism and the proteins involved seemed to have a low turnover."}
{"id": "PMID:14926", "title": "Purification and some properties of an extracellular alpha-amylase from Bacteroides amylophilus.", "content": "A medium  was developed to obtain maximum yields of extracellular amylase from Bacteroides amylophilus 70. Crude enzyme preparation, obtained by ammonium sulfate precipitation of cell-free broth, contained six amylolytic isoenzymes that were detected by isoelectric focusing and polyacrylamide gel electrophoresis. One of these amylases was purified by diethylaminoethyl-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel filtration techniques. Some properties of the purified extracellular alpha-amylase were: optimum pH, 6.3; optimum temperature, 43 degrees C: PH stability range, 5.8 to 7.5; isoelectric point, pH 4.6; molecular weight, 92,000 (by sodium dodecyl sulfatedisc gel electrophoresis); and sugars causing inhibition, cyclomaltoheptaose, cyclomaltohexaose, and alpha-d-phenylglucoside. In addition, Ca2+ and Co2+ were strong activators,and Hg2+ was a strong inhibitior; all other cations were slightly stimulatory. Dialysis against 0.01 M ethylenediaminetetraacetic acid caused a 58% loss of activity that was restored to 92% of the original by the addition of 0.04 M Ca2+. The enzyme affected a blue-value-reducing-value curve characteristic of alpha-type amylases. The relative rates of hydrolysis of amylose, soluble starch, amylopectin, and dextrin were 100, 97, 92, and 60%, respectively; Michaelis constants for these substrates were 18.2, 18.7, 18.2, and 16.7 mumol of d-glucosidic bond/liter, respectively. The enzyme degraded maize (corn) starch granules to some extent and had relatively little activity on potato starch granules.", "contents": "Purification and some properties of an extracellular alpha-amylase from Bacteroides amylophilus. A medium  was developed to obtain maximum yields of extracellular amylase from Bacteroides amylophilus 70. Crude enzyme preparation, obtained by ammonium sulfate precipitation of cell-free broth, contained six amylolytic isoenzymes that were detected by isoelectric focusing and polyacrylamide gel electrophoresis. One of these amylases was purified by diethylaminoethyl-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel filtration techniques. Some properties of the purified extracellular alpha-amylase were: optimum pH, 6.3; optimum temperature, 43 degrees C: PH stability range, 5.8 to 7.5; isoelectric point, pH 4.6; molecular weight, 92,000 (by sodium dodecyl sulfatedisc gel electrophoresis); and sugars causing inhibition, cyclomaltoheptaose, cyclomaltohexaose, and alpha-d-phenylglucoside. In addition, Ca2+ and Co2+ were strong activators,and Hg2+ was a strong inhibitior; all other cations were slightly stimulatory. Dialysis against 0.01 M ethylenediaminetetraacetic acid caused a 58% loss of activity that was restored to 92% of the original by the addition of 0.04 M Ca2+. The enzyme affected a blue-value-reducing-value curve characteristic of alpha-type amylases. The relative rates of hydrolysis of amylose, soluble starch, amylopectin, and dextrin were 100, 97, 92, and 60%, respectively; Michaelis constants for these substrates were 18.2, 18.7, 18.2, and 16.7 mumol of d-glucosidic bond/liter, respectively. The enzyme degraded maize (corn) starch granules to some extent and had relatively little activity on potato starch granules."}
{"id": "PMID:14927", "title": "Formation of glutamine from [13n]ammonia, [13n]dinitrogen, and [14C]glutamate by heterocysts isolated from Anabaena cylindrica.", "content": "A method is described for the isolation of metabolically active heterocysts from Anabaena cylindrica. These isolated heterocysts accounted for up to 34% of the acetylene-reducing activity of whole filaments and had a specific activity of up to 1,560 nmol of C2H4 formed per mg of heterocyst chlorphyll per min. Activity of glutamine synthetase was coupled to activity of nitrogenase in isolated heterocysts as shown by acetylene-inhibitable formation of [13N]NH3 and of amidelabeled [13N]glutamine form [13N]N2. A method is also described for the production of 6-mCi amounts of [13N]NH3. Isolated heterocysts formed [13N]glutamine from [13N]NH3 and glutamate, and [14C]glutamine from NH3 and [14C]glutamate, in the presence of magnesium adenosine 5'-triphosphate. Methionine sulfoximine strongly inhibited these syntheses. Glutamate synthase is, after nitrogenase and glutamine synthetase, the third sequential enzyme involved in the assimilation of N2 by intact filaments. However, the kinetics of solubilization of the activity of glutamate synthase during cavitation of suspensions of A. cylindrica indicated that very little, if any, of the activity of that enzyme was located in heterocysts. Concordantly, isolated heterocysts failed to form substantial amounts of radioactive glutamate from either [13N]glutamine or alph-[14C]ketoglutarate in the presence of other substrates and cofactors of the glutamate synthase reaction. However, they formed [14C]glutamate rapidly from alpha-[14C]ketoglutarate by aminotransferase reactions, with various amino acids as the nitrogen donor. The implication of these findings with regard to the identities of the substances moving between heterocysts and vegetative cells are discussed.", "contents": "Formation of glutamine from [13n]ammonia, [13n]dinitrogen, and [14C]glutamate by heterocysts isolated from Anabaena cylindrica. A method is described for the isolation of metabolically active heterocysts from Anabaena cylindrica. These isolated heterocysts accounted for up to 34% of the acetylene-reducing activity of whole filaments and had a specific activity of up to 1,560 nmol of C2H4 formed per mg of heterocyst chlorphyll per min. Activity of glutamine synthetase was coupled to activity of nitrogenase in isolated heterocysts as shown by acetylene-inhibitable formation of [13N]NH3 and of amidelabeled [13N]glutamine form [13N]N2. A method is also described for the production of 6-mCi amounts of [13N]NH3. Isolated heterocysts formed [13N]glutamine from [13N]NH3 and glutamate, and [14C]glutamine from NH3 and [14C]glutamate, in the presence of magnesium adenosine 5'-triphosphate. Methionine sulfoximine strongly inhibited these syntheses. Glutamate synthase is, after nitrogenase and glutamine synthetase, the third sequential enzyme involved in the assimilation of N2 by intact filaments. However, the kinetics of solubilization of the activity of glutamate synthase during cavitation of suspensions of A. cylindrica indicated that very little, if any, of the activity of that enzyme was located in heterocysts. Concordantly, isolated heterocysts failed to form substantial amounts of radioactive glutamate from either [13N]glutamine or alph-[14C]ketoglutarate in the presence of other substrates and cofactors of the glutamate synthase reaction. However, they formed [14C]glutamate rapidly from alpha-[14C]ketoglutarate by aminotransferase reactions, with various amino acids as the nitrogen donor. The implication of these findings with regard to the identities of the substances moving between heterocysts and vegetative cells are discussed."}
{"id": "PMID:14928", "title": "Measurement of the pH of frozen buffer solutions by using pH indicators.", "content": "A method was established to estimate the pH change of several buffers solutions on freezing by using a combination of pH indicators. Among more than 30 buffers solutions examined, almost half exhibited a pH change in the temperature range between freezing point and 220 degrees K; the results were tabulated. Glycerol was found to suppress the pH changes because of its \"salt buffer\" effect.", "contents": "Measurement of the pH of frozen buffer solutions by using pH indicators. A method was established to estimate the pH change of several buffers solutions on freezing by using a combination of pH indicators. Among more than 30 buffers solutions examined, almost half exhibited a pH change in the temperature range between freezing point and 220 degrees K; the results were tabulated. Glycerol was found to suppress the pH changes because of its \"salt buffer\" effect."}
{"id": "PMID:14929", "title": "Mathematical analysis of ligand-induced monomerization and dimerization in the monomer dimer equilibrium of proteins. Application to D-amino acid oxidase.", "content": "We have mathematically analyzed ligand-induced monomerization and dimerization in a protein monomer-dimer equilibrium system, in which the monomer has one and the dimer two binding sites. These dimer sites have the same binding constants for the first ligand but may cooperatively interact when one of them is occupied by a ligand molecule. In this system, the apparent dimerization constant and the apparent molecular weight are functions of free ligand concentration, and depend on the intrinsic binding constants of the ligand molecule to the monomer and the dimer. The behavior of these functions is classified into 17 cases according to the values of the three intrinsic binding constants, and some calculated examples are shown graphically for selected parameters. The theory was also applied to D-amino acid oxidase [EC 1.4.3.3], a flavoprotein, and the pH dependence of the apparent dimerization constant and the apparent molecular weight in the presence of ligand, p-aminobenzoate, were studied theoretically using parameters obtained in our previous experiments (5).", "contents": "Mathematical analysis of ligand-induced monomerization and dimerization in the monomer dimer equilibrium of proteins. Application to D-amino acid oxidase. We have mathematically analyzed ligand-induced monomerization and dimerization in a protein monomer-dimer equilibrium system, in which the monomer has one and the dimer two binding sites. These dimer sites have the same binding constants for the first ligand but may cooperatively interact when one of them is occupied by a ligand molecule. In this system, the apparent dimerization constant and the apparent molecular weight are functions of free ligand concentration, and depend on the intrinsic binding constants of the ligand molecule to the monomer and the dimer. The behavior of these functions is classified into 17 cases according to the values of the three intrinsic binding constants, and some calculated examples are shown graphically for selected parameters. The theory was also applied to D-amino acid oxidase [EC 1.4.3.3], a flavoprotein, and the pH dependence of the apparent dimerization constant and the apparent molecular weight in the presence of ligand, p-aminobenzoate, were studied theoretically using parameters obtained in our previous experiments (5)."}
{"id": "PMID:14930", "title": "Studies on the microsomal electron-transport system of anaerobically grown yeast. IV. Purification and characterization of NADH-cytochrome b5 reductase.", "content": "The presence of NADH-cytochrome b5 reductase [EC 1.6.2.2] in microsomes from anaerobically grown yeast was confirmed by its isolation and purification. The purified preparation of the reductase showed an apparent molecular weight of 27,000 daltons. The reductase appeared to contain loosely-bound FAD as a prosthetic group. The reductase required NADH as a specific electron donor, and could reduce some redox dyes as well as cytochrom b5. The reductase, however, could not reduce cytochrome c. Michaelis constants of the reductase for NADH and calf liver cytochrome b5 were 6.3 and 1.5 micron M, respectively, and optimal pH for cytochrome b5 reduction was 5.6. Although some differences exist between the properties of NADH-cytochrome b5 reductase from yeast and from mammalia, the results indicate a functional similarity of the present enzyme to mammalian NADH-cytochrome b5 reductase in the microsomal electron-transport system.", "contents": "Studies on the microsomal electron-transport system of anaerobically grown yeast. IV. Purification and characterization of NADH-cytochrome b5 reductase. The presence of NADH-cytochrome b5 reductase [EC 1.6.2.2] in microsomes from anaerobically grown yeast was confirmed by its isolation and purification. The purified preparation of the reductase showed an apparent molecular weight of 27,000 daltons. The reductase appeared to contain loosely-bound FAD as a prosthetic group. The reductase required NADH as a specific electron donor, and could reduce some redox dyes as well as cytochrom b5. The reductase, however, could not reduce cytochrome c. Michaelis constants of the reductase for NADH and calf liver cytochrome b5 were 6.3 and 1.5 micron M, respectively, and optimal pH for cytochrome b5 reduction was 5.6. Although some differences exist between the properties of NADH-cytochrome b5 reductase from yeast and from mammalia, the results indicate a functional similarity of the present enzyme to mammalian NADH-cytochrome b5 reductase in the microsomal electron-transport system."}
{"id": "PMID:14931", "title": "Studies on the microsomal electron-transport system of anaerobically grown yeast. V. Purification and characterization of NADPH-cytochrome c reductase.", "content": "A flavoprotein catalyzing the reduction of cytochrome c by NADPH was solubilized and purified from microsomes of yeast grown anaerobically. The cytochrome c reductase had an apparent molecular weight of 70,000 daltons and contained one mole each of FAD and FMN per mole of enzyme. The reductase could reduce some redox dyes as well as cytochrome c, but could not catalyze the reduction of cytochrome b5. The reductase preparation also catalyzed the oxidation of NADPH with molecular oxygen in the presence of a catalytic amount of 2-methyl-1,4-naphthoquinone (menadione). The Michaelis constants of the reductase for NADPH and cytochrome c were determined to be 32.4 and 3.4 micron M, respectively, and the optimal pH for cytochrome c reduction was 7.8 to 8.0. It was concluded that yeast NADPH-cytochrome c reductase is in many respects similar to the liver microsomal reductase which acts as an NADPH-cytochrome P-450 reductase [EC 1.6.2.4].", "contents": "Studies on the microsomal electron-transport system of anaerobically grown yeast. V. Purification and characterization of NADPH-cytochrome c reductase. A flavoprotein catalyzing the reduction of cytochrome c by NADPH was solubilized and purified from microsomes of yeast grown anaerobically. The cytochrome c reductase had an apparent molecular weight of 70,000 daltons and contained one mole each of FAD and FMN per mole of enzyme. The reductase could reduce some redox dyes as well as cytochrome c, but could not catalyze the reduction of cytochrome b5. The reductase preparation also catalyzed the oxidation of NADPH with molecular oxygen in the presence of a catalytic amount of 2-methyl-1,4-naphthoquinone (menadione). The Michaelis constants of the reductase for NADPH and cytochrome c were determined to be 32.4 and 3.4 micron M, respectively, and the optimal pH for cytochrome c reduction was 7.8 to 8.0. It was concluded that yeast NADPH-cytochrome c reductase is in many respects similar to the liver microsomal reductase which acts as an NADPH-cytochrome P-450 reductase [EC 1.6.2.4]."}
{"id": "PMID:14932", "title": "I-protein, a new regulatory protein from vertebrate skeletal muscle. III. Function.", "content": "I-protein inhibited theMg-activated ATPase [EC 3.6.1.3] activity of actinomyosin by approximately 50% at low ionic strength. Concomitantly, the onset of superprecipitation was retarded. I-protein was found to bind to myosin, but not to F-actin. The inhibitory action of I-protein occurred only in the absence of Ca ions in the troponintropomyosin-actin myosin system. Addition of Ca ions abolished the effect. Thus, it is very likely that I-protein prevents unnecessary hydrolysis of ATP in the relaxed state of muscle.", "contents": "I-protein, a new regulatory protein from vertebrate skeletal muscle. III. Function. I-protein inhibited theMg-activated ATPase [EC 3.6.1.3] activity of actinomyosin by approximately 50% at low ionic strength. Concomitantly, the onset of superprecipitation was retarded. I-protein was found to bind to myosin, but not to F-actin. The inhibitory action of I-protein occurred only in the absence of Ca ions in the troponintropomyosin-actin myosin system. Addition of Ca ions abolished the effect. Thus, it is very likely that I-protein prevents unnecessary hydrolysis of ATP in the relaxed state of muscle."}
{"id": "PMID:14933", "title": "Kinetic studies on the ADP-ATP exchange reaction catalyzed by Na+, K+-dependent ATPase. Evidence for the K.S.T. mechanism with two enzyme-ATP complexes and two phosphorylated intermediates of high-energy type.", "content": "The kinetic properties of the [3H]ADP-ATP exchange reaction catalyzed by Na+, K+-dependent ATPase [EC 3.6.1,3] were investigated, using NaI-treated microsomes from bovine brain, and the following results were obtained. 1. The rates of the Na+-dependent exchange reaction in the steady state were measured in a solution containing 45 micronM free Mg2+, 100 mMNaCl, 80 micronM ATP, and 160 micronM ADP at pH 6.5 and 4-5 degrees. The rate and amount of decrease in phosphorylated intermediate on adding ADP, i.e., the amount of ADP-sensitive EP, were measured while varying one of the reaction parameters and fixing the others mentioned above. Plots of the exchange rate and the amount of ADP-sensitive EP against the logarithm of free Mg2+ concentration gave bell-shaped curves with maximum values at 50-60 micronM free Mg2+. Plots of the exchange rate and the amount of ADP-sensitive EP against pH also gave bell-shaped curves with maximum values at pH 6.9-7. They both increased with increase in the concentration of NaCl to maximum values at 150-200 mM NaCl, and then decreased rapidly with increase in the NaCl concentration above 200 mM. The dependences of the exchange rate and the amount of ADP-sensitive EP on the concentration of ADP followed the Michaelis-Menten equation, and the Michaelis constants Km, for both were 43 micronM. The dependence of the exchange rate on the ATP concentration also followed the Michaelis-Menten equation, and the Km value was 30 micronM. The amount of ADP-sensitive EP increased with increase in the ATP concentration, and reached a maximum value at about 5 micronM ATP. 2. The N+-dependent [3H]ADP-ATP exchange reaction was started by adding [3H]ADP to EP at low Mg2+-concentration. The reaction consisted of a rapid initial phase and a slow steady phase. The amount of [3H]ATP formed during the rapid initial phase, i.e. the size of the ATP burst, was equal to that of ADP-sensitive EP, and was proportional to the rate in the steady state. At high Mg2+ concentration, the rate of Na+-dependent exchange in the steady state was almost zero, and EP did not show any ADP sensitivity. However, rapid formation of [3H]ATP was observed in the pre-steady state, and the size of the ATP burst increased with increase in the KCl concentration. From these findings, we concluded that an enzyme-ATP complex (E2ATP) formed at low Mg2+ concentration is in equilibrium with EP + ADP, that the rate-limiting step for the exchange reaction is the release of ATP from the enzyme-ATP complex, that the ADP-insensitive EP (formula: see text) produced at high Mg2+ concentration is in equilibrium with the enzyme-ATP complex, and that the equilibrium shifts towards the enzyme-ATP complex on adding KCl. Actually, the ratio of the size of the ATP burst to the amount of EP was equal to the reciprocal of the equilibrium constant of step (formula: see text), determined by a method previously reported by us.", "contents": "Kinetic studies on the ADP-ATP exchange reaction catalyzed by Na+, K+-dependent ATPase. Evidence for the K.S.T. mechanism with two enzyme-ATP complexes and two phosphorylated intermediates of high-energy type. The kinetic properties of the [3H]ADP-ATP exchange reaction catalyzed by Na+, K+-dependent ATPase [EC 3.6.1,3] were investigated, using NaI-treated microsomes from bovine brain, and the following results were obtained. 1. The rates of the Na+-dependent exchange reaction in the steady state were measured in a solution containing 45 micronM free Mg2+, 100 mMNaCl, 80 micronM ATP, and 160 micronM ADP at pH 6.5 and 4-5 degrees. The rate and amount of decrease in phosphorylated intermediate on adding ADP, i.e., the amount of ADP-sensitive EP, were measured while varying one of the reaction parameters and fixing the others mentioned above. Plots of the exchange rate and the amount of ADP-sensitive EP against the logarithm of free Mg2+ concentration gave bell-shaped curves with maximum values at 50-60 micronM free Mg2+. Plots of the exchange rate and the amount of ADP-sensitive EP against pH also gave bell-shaped curves with maximum values at pH 6.9-7. They both increased with increase in the concentration of NaCl to maximum values at 150-200 mM NaCl, and then decreased rapidly with increase in the NaCl concentration above 200 mM. The dependences of the exchange rate and the amount of ADP-sensitive EP on the concentration of ADP followed the Michaelis-Menten equation, and the Michaelis constants Km, for both were 43 micronM. The dependence of the exchange rate on the ATP concentration also followed the Michaelis-Menten equation, and the Km value was 30 micronM. The amount of ADP-sensitive EP increased with increase in the ATP concentration, and reached a maximum value at about 5 micronM ATP. 2. The N+-dependent [3H]ADP-ATP exchange reaction was started by adding [3H]ADP to EP at low Mg2+-concentration. The reaction consisted of a rapid initial phase and a slow steady phase. The amount of [3H]ATP formed during the rapid initial phase, i.e. the size of the ATP burst, was equal to that of ADP-sensitive EP, and was proportional to the rate in the steady state. At high Mg2+ concentration, the rate of Na+-dependent exchange in the steady state was almost zero, and EP did not show any ADP sensitivity. However, rapid formation of [3H]ATP was observed in the pre-steady state, and the size of the ATP burst increased with increase in the KCl concentration. From these findings, we concluded that an enzyme-ATP complex (E2ATP) formed at low Mg2+ concentration is in equilibrium with EP + ADP, that the rate-limiting step for the exchange reaction is the release of ATP from the enzyme-ATP complex, that the ADP-insensitive EP (formula: see text) produced at high Mg2+ concentration is in equilibrium with the enzyme-ATP complex, and that the equilibrium shifts towards the enzyme-ATP complex on adding KCl. Actually, the ratio of the size of the ATP burst to the amount of EP was equal to the reciprocal of the equilibrium constant of step (formula: see text), determined by a method previously reported by us."}
{"id": "PMID:14934", "title": "Spontaneous deamidation of a protein antibiotic, neocarzinostatin, at weakly acidic pH. Conversion to a homologous inactive preneocarzinostatin due to change of asparagine 83 to aspartic acid 83 accompanied by conformational and biological alterations.", "content": "The amide content of neocarzinostatin (NCS), an antitumor protein, has been determined by analysing asparagine and glutamine in the Pronase-aminopeptidase M digests of tetra-S-carboxymethyl-NCS and carboxyl-modified NCS (modified with a water-soluble carbodiimide and [14C]glycine methyl ester). Preneocarzinostatin (PRE) was separated and purified from a crude NCS preparation by CM-cellulose column chromatography. PRE was found to contain one mole less asparagine than NCS, and asparagine was deamidated to aspartic acid in PRE. A time-dependent conversion of NCS to PRE at pH 3.2 at 4 degrees or in 0.1 M acetic acid at 26 degrees was studied in two ways; first, by quantitative determination of NCS and PRE by CM-cellulose column chromatography and second, by following the release of free NH3 during dialysis in an air-tight container. Within experimental error, PRE was indistinguishable from NCS in amino acid content after acid hydrolysis, as well as in apparent molecular weight as determined by SDS-disc gel electrophoresis (10% acrylamide), and N- and C-terminal amino acid residues. Both NCS and PRE shared a common antigenicity as determined by Ouchterlony's agar diffusion method. Only a slight difference between the two in electrophoresis on a cellulose acetate membrane and on a peptide map of the tryptic digest was demonstrated. PRE, however, was completely devoid of biological activity. In addition to the chromatographic difference, a conformational difference was observed by CD spectroscopy, namely, an apparently looser structure of PRE was indicated by the shallowness of the trough in the 240-265 nm region. This interpretation was supported by the finding that digestions by Pronase were more extensive with PRE than with NCS. These results indicate an important role of the single asparagine residue (Asn 83) of NCS in the biological activity, which is evidently governed by the conformation.", "contents": "Spontaneous deamidation of a protein antibiotic, neocarzinostatin, at weakly acidic pH. Conversion to a homologous inactive preneocarzinostatin due to change of asparagine 83 to aspartic acid 83 accompanied by conformational and biological alterations. The amide content of neocarzinostatin (NCS), an antitumor protein, has been determined by analysing asparagine and glutamine in the Pronase-aminopeptidase M digests of tetra-S-carboxymethyl-NCS and carboxyl-modified NCS (modified with a water-soluble carbodiimide and [14C]glycine methyl ester). Preneocarzinostatin (PRE) was separated and purified from a crude NCS preparation by CM-cellulose column chromatography. PRE was found to contain one mole less asparagine than NCS, and asparagine was deamidated to aspartic acid in PRE. A time-dependent conversion of NCS to PRE at pH 3.2 at 4 degrees or in 0.1 M acetic acid at 26 degrees was studied in two ways; first, by quantitative determination of NCS and PRE by CM-cellulose column chromatography and second, by following the release of free NH3 during dialysis in an air-tight container. Within experimental error, PRE was indistinguishable from NCS in amino acid content after acid hydrolysis, as well as in apparent molecular weight as determined by SDS-disc gel electrophoresis (10% acrylamide), and N- and C-terminal amino acid residues. Both NCS and PRE shared a common antigenicity as determined by Ouchterlony's agar diffusion method. Only a slight difference between the two in electrophoresis on a cellulose acetate membrane and on a peptide map of the tryptic digest was demonstrated. PRE, however, was completely devoid of biological activity. In addition to the chromatographic difference, a conformational difference was observed by CD spectroscopy, namely, an apparently looser structure of PRE was indicated by the shallowness of the trough in the 240-265 nm region. This interpretation was supported by the finding that digestions by Pronase were more extensive with PRE than with NCS. These results indicate an important role of the single asparagine residue (Asn 83) of NCS in the biological activity, which is evidently governed by the conformation."}
{"id": "PMID:14935", "title": "Kallikrein inhibitors in rat plasma.", "content": "The kallikrein inhibitor contents of human and animal plasma were determined with glandular kallikreins [EC 3.4.21.8]. One ml of plasma could inactivate 20-700 kallikrein units (KU). Rat plasma was the most potent and inactivated 230-700 KU. However, no enzyme capable of inactivating kallikrein could be found in this plasma. Two fractions which inhibited hog pancreatic kallikrein, a fraction corresponding to alpha2-macroglobulin and a fraction which was eluted prior to albumin, were separated from rat plasma by Sephadex G-200 gel filtration. The former inhibitor could inhibit hog pancreatic kallikrein action on Nalpha-benzoyl-L-arginine ethyl ester (BAEE) as well as in the dog vasodilator assay. The other inhibitor was partially purified from rat plasma. One mg of the preparation inhibited 67 KU and the hydrolysis of 5.8 micronmoles/min of BAEE by hog pancreatic kallikrein [EC 3.4.21.8]. The inhibitor also inhibited other glandular and plasma kallikreins, trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], etc. The optimal pH of the inhibitor was 7.5-8. The inhibitor was unstable below pH 5, and was destroyed by heating at temperature above 60 degrees. The isoelectric point of the inhibitor was determined by Ampholine focusing to be 4.4, and its molecular weight was estimated to be 73,000 by Sephadex G-100 and G-150 filtrations. Several experimental results suggested that this inhibitor differed from alpha1-antitrypsin.", "contents": "Kallikrein inhibitors in rat plasma. The kallikrein inhibitor contents of human and animal plasma were determined with glandular kallikreins [EC 3.4.21.8]. One ml of plasma could inactivate 20-700 kallikrein units (KU). Rat plasma was the most potent and inactivated 230-700 KU. However, no enzyme capable of inactivating kallikrein could be found in this plasma. Two fractions which inhibited hog pancreatic kallikrein, a fraction corresponding to alpha2-macroglobulin and a fraction which was eluted prior to albumin, were separated from rat plasma by Sephadex G-200 gel filtration. The former inhibitor could inhibit hog pancreatic kallikrein action on Nalpha-benzoyl-L-arginine ethyl ester (BAEE) as well as in the dog vasodilator assay. The other inhibitor was partially purified from rat plasma. One mg of the preparation inhibited 67 KU and the hydrolysis of 5.8 micronmoles/min of BAEE by hog pancreatic kallikrein [EC 3.4.21.8]. The inhibitor also inhibited other glandular and plasma kallikreins, trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], etc. The optimal pH of the inhibitor was 7.5-8. The inhibitor was unstable below pH 5, and was destroyed by heating at temperature above 60 degrees. The isoelectric point of the inhibitor was determined by Ampholine focusing to be 4.4, and its molecular weight was estimated to be 73,000 by Sephadex G-100 and G-150 filtrations. Several experimental results suggested that this inhibitor differed from alpha1-antitrypsin."}
{"id": "PMID:14936", "title": "Studies on the catalytic action of poly-alpha-amino acids. VII. Stereospecificity in the enzyme-like hydrolysis of benzoyl-L-(D)-arginine-p-nitroanilides by copoly (Cys, Glu).", "content": "The substrate specificity in the hydrolysis of L-, DL-, and D-BAPA (benzoylarginine-p-nitro-anilide) by copoly (L-Cys, L-Glu) and copoly (D-Cys, D-Glu) was studied, and enzyme-like stereospecific hydrolyses by poly-alpha-amino acids were identified for the first time. The L-type copolymer hydrolyzed L-BAPA faster than D-BAPA and the rates (v) of BAPA hydrolyses by L-type copolymer were found to be in the order vL greater than vDL greater than vD. On the other hand, the D-type copolymer hydrolysed D-BAPA faster than L-BAPA and the rates of BAPA hydrolyses by D-type copolymer were in the order vD greater than vDL greater than vL. In all cases, the reaction followed Michaelis-Menten kinetics when the substrate concentration was corrected, and the optimum conditions of the reaction were pH 6.0 and 40 degrees. The activity appeared after a certain amount of BAPA had combined with the polymer. D- and L-substrates combine competitively with the polymer and the different rates of hydrolysis are presumably due to the different substrate configurations in relation to the conformation of the active site in the polymer. The polymer shows activity near the range of random coil conformation, where some alpha-helical conformation is still present. Only some of the cysteine residues in the copolymer are involved in the hydrolytic activity.", "contents": "Studies on the catalytic action of poly-alpha-amino acids. VII. Stereospecificity in the enzyme-like hydrolysis of benzoyl-L-(D)-arginine-p-nitroanilides by copoly (Cys, Glu). The substrate specificity in the hydrolysis of L-, DL-, and D-BAPA (benzoylarginine-p-nitro-anilide) by copoly (L-Cys, L-Glu) and copoly (D-Cys, D-Glu) was studied, and enzyme-like stereospecific hydrolyses by poly-alpha-amino acids were identified for the first time. The L-type copolymer hydrolyzed L-BAPA faster than D-BAPA and the rates (v) of BAPA hydrolyses by L-type copolymer were found to be in the order vL greater than vDL greater than vD. On the other hand, the D-type copolymer hydrolysed D-BAPA faster than L-BAPA and the rates of BAPA hydrolyses by D-type copolymer were in the order vD greater than vDL greater than vL. In all cases, the reaction followed Michaelis-Menten kinetics when the substrate concentration was corrected, and the optimum conditions of the reaction were pH 6.0 and 40 degrees. The activity appeared after a certain amount of BAPA had combined with the polymer. D- and L-substrates combine competitively with the polymer and the different rates of hydrolysis are presumably due to the different substrate configurations in relation to the conformation of the active site in the polymer. The polymer shows activity near the range of random coil conformation, where some alpha-helical conformation is still present. Only some of the cysteine residues in the copolymer are involved in the hydrolytic activity."}
{"id": "PMID:14937", "title": "DTNB modification of SH groups of isocitrate dehydrogenase from Bacillus stearothermophilus purified by affinity chromatography.", "content": "A new method of affinity chromatography using blue dextran-Sepharose 4B resin was established to purify NADP+-dependent isocitrate dehydrogenase [EC 1.1.1.42] from Bacillus stearothermophilus in high yield. The purified preparation was found to be homogeneous on disc gel electrophoresis. The SH groups of the enzyme were modified with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) to determine the number of SH groups per molecule and their contribution to the enzyme activity. One SH group was titrated with DTNB per subunit (the native enzyme consisted of two subunits) and after complete denaturation with 4 M guanidine-HCl the number of titratable SH groups remained unchanged. ORD and CD measurements showed that the alpha-helical conformation of the polypeptide backbone was unaffected by DTNB modification, though the near ultraviolet CD spectrum was evidently altered. The fluorescence derived from tryptophanyl residue(s) was quenched by the modification to 30% of the native level, which may indicate the presence of SH in the vicinity of tryptophanyl residue(s). A remarkable decrease of the enzyme activity was detected upon modification with DTNB, but there was some discrepancy between the rate of inactivation and that of modification of SH groups. The presence of substrate and Mg2+ gave partial protection against modification of the SH groups by DTNB. Complete protection of the native enzyme activity against heating at 65 degrees was observed in the presence of substrate and Mg2+, but the thermostability of the enzyme was markedly reduced by modification of the SH groups.", "contents": "DTNB modification of SH groups of isocitrate dehydrogenase from Bacillus stearothermophilus purified by affinity chromatography. A new method of affinity chromatography using blue dextran-Sepharose 4B resin was established to purify NADP+-dependent isocitrate dehydrogenase [EC 1.1.1.42] from Bacillus stearothermophilus in high yield. The purified preparation was found to be homogeneous on disc gel electrophoresis. The SH groups of the enzyme were modified with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) to determine the number of SH groups per molecule and their contribution to the enzyme activity. One SH group was titrated with DTNB per subunit (the native enzyme consisted of two subunits) and after complete denaturation with 4 M guanidine-HCl the number of titratable SH groups remained unchanged. ORD and CD measurements showed that the alpha-helical conformation of the polypeptide backbone was unaffected by DTNB modification, though the near ultraviolet CD spectrum was evidently altered. The fluorescence derived from tryptophanyl residue(s) was quenched by the modification to 30% of the native level, which may indicate the presence of SH in the vicinity of tryptophanyl residue(s). A remarkable decrease of the enzyme activity was detected upon modification with DTNB, but there was some discrepancy between the rate of inactivation and that of modification of SH groups. The presence of substrate and Mg2+ gave partial protection against modification of the SH groups by DTNB. Complete protection of the native enzyme activity against heating at 65 degrees was observed in the presence of substrate and Mg2+, but the thermostability of the enzyme was markedly reduced by modification of the SH groups."}
{"id": "PMID:14938", "title": "Kinetics of conformational change of troponin-C induced by proton binding or removal in the absence of calcium ions.", "content": "The kinetics of the conformational change of troponin-C induced by binding or removal of protons was studied by a stopped-flow pH-jump spectrofluorometric method. In the pH-down experiment (to investigate the kinetics of conformational change from the deprotonated state to the protonated state), a single first-order reaction with a rate constant and amplitude of 1.75-2.4 sec-1 and around 10% respectively, was observed. On the other hand, two first-order reactions with rate constants of 0.84-1.6 sec-1 and 0.08-0.4 sec-1 were observed in the pH-up experiment, the total amplitudes of these reactions being around 10-20%. The pH dependences of the rate constants of these reactions were analyzed in terms of a three-species mechanism.", "contents": "Kinetics of conformational change of troponin-C induced by proton binding or removal in the absence of calcium ions. The kinetics of the conformational change of troponin-C induced by binding or removal of protons was studied by a stopped-flow pH-jump spectrofluorometric method. In the pH-down experiment (to investigate the kinetics of conformational change from the deprotonated state to the protonated state), a single first-order reaction with a rate constant and amplitude of 1.75-2.4 sec-1 and around 10% respectively, was observed. On the other hand, two first-order reactions with rate constants of 0.84-1.6 sec-1 and 0.08-0.4 sec-1 were observed in the pH-up experiment, the total amplitudes of these reactions being around 10-20%. The pH dependences of the rate constants of these reactions were analyzed in terms of a three-species mechanism."}
{"id": "PMID:14939", "title": "Self-assembly of myosin in vitro caused by rapid dilution. Effects of hydrogen ion, potassium chloride, and protein concentrations.", "content": "The in vitro assembly of rabbit skeletal myosin was studied by flow birefringence. Filaments were obtained from a solution of myosin in 0.5 M KCl by rapid dilution to lower ionic strength. In most cases, the filament length as determined from extinction angle measurements increased or decreased gradually for about 1 h after dilution, depending on pH, KCl concentration and the previous history. The filament length (l) immediately after dilution also showed a marked dependence on pH, KCl concentration and protein concentration (c) at the moment of assembly. The general characteristics obtained from our limited study (0.04-6.0 mg/ml) show three distinctive modes of effect of the protein concentration on the filament length: d logl/d log c is positive (0.1-1) at small c, negative (from -1 to -0.2) at intermediate c, and zero or slightly positive (0.0-0.3) at large c. Lowering of the KCl concentration (75-250 mM) as well as increase of the hydrogen ion concentration (pH 6-8) influenced the filament length in qualitatively the same manner as increase of the protein concentration. A model of the assembly reaction of myosin in which the polarity of filaments is crucial was constructed and shown to give qualitatively the experimental dependence of the filament length on the protein concentration.", "contents": "Self-assembly of myosin in vitro caused by rapid dilution. Effects of hydrogen ion, potassium chloride, and protein concentrations. The in vitro assembly of rabbit skeletal myosin was studied by flow birefringence. Filaments were obtained from a solution of myosin in 0.5 M KCl by rapid dilution to lower ionic strength. In most cases, the filament length as determined from extinction angle measurements increased or decreased gradually for about 1 h after dilution, depending on pH, KCl concentration and the previous history. The filament length (l) immediately after dilution also showed a marked dependence on pH, KCl concentration and protein concentration (c) at the moment of assembly. The general characteristics obtained from our limited study (0.04-6.0 mg/ml) show three distinctive modes of effect of the protein concentration on the filament length: d logl/d log c is positive (0.1-1) at small c, negative (from -1 to -0.2) at intermediate c, and zero or slightly positive (0.0-0.3) at large c. Lowering of the KCl concentration (75-250 mM) as well as increase of the hydrogen ion concentration (pH 6-8) influenced the filament length in qualitatively the same manner as increase of the protein concentration. A model of the assembly reaction of myosin in which the polarity of filaments is crucial was constructed and shown to give qualitatively the experimental dependence of the filament length on the protein concentration."}
{"id": "PMID:14940", "title": "Temperature induced transition of the pH-activity curve of heavy meromyosin adenosine triphosphatase and inosine triphosphatase.", "content": "The pH-activity curve of heavy meromyosin ATPase [EC 3.6.1.3] was measured at various temperatures. The pH-activity curve at higher temperatures showed a maximum at low pH and a minimum at pH 7 to 8 as has been already reported. At lower temperatures it was sigmoidal in shape, similar to a simple dissociation curve of pKa 6 to 7. The pH-activity curve at intermediate temperatures appeared to be inbetween the two extreme shapes. These changes in pH-activity curve with temperature were found to be common in the presence of divalent cations such as Mg2+, Mn2+, and Ca2+. The ATPase mechanism may be identical in the presence of any divalent cation, and the rate determining step revealing the steady state rate alters by changing the temperature. The transition temperatures estimated at pH 8 were 10 degrees, 8 degrees, and about 5 degrees in the presence of MnCl2, CaCl2, and MgCl2, respectively. The difference in the temperature coefficients above and below the transition temperature was most distinct in the presence of MnCl2, and vague in the presence of CaCl2. A similar change of pH-activity curve with temperature was found with heavy meromyosin ITPase in the presence of MgCl2.", "contents": "Temperature induced transition of the pH-activity curve of heavy meromyosin adenosine triphosphatase and inosine triphosphatase. The pH-activity curve of heavy meromyosin ATPase [EC 3.6.1.3] was measured at various temperatures. The pH-activity curve at higher temperatures showed a maximum at low pH and a minimum at pH 7 to 8 as has been already reported. At lower temperatures it was sigmoidal in shape, similar to a simple dissociation curve of pKa 6 to 7. The pH-activity curve at intermediate temperatures appeared to be inbetween the two extreme shapes. These changes in pH-activity curve with temperature were found to be common in the presence of divalent cations such as Mg2+, Mn2+, and Ca2+. The ATPase mechanism may be identical in the presence of any divalent cation, and the rate determining step revealing the steady state rate alters by changing the temperature. The transition temperatures estimated at pH 8 were 10 degrees, 8 degrees, and about 5 degrees in the presence of MnCl2, CaCl2, and MgCl2, respectively. The difference in the temperature coefficients above and below the transition temperature was most distinct in the presence of MnCl2, and vague in the presence of CaCl2. A similar change of pH-activity curve with temperature was found with heavy meromyosin ITPase in the presence of MgCl2."}
{"id": "PMID:14941", "title": "Temperature dependence of the decay of the UV absorption difference spectrum of heavy meromyosin induced by adenosine triphosphate and inosine triphosphate.", "content": "The UV absorption difference spectrum of heavy meromyosin induced by ATP was measured at various temperatures. At higher temperatures, the difference spectrum formed rapidly after adding ATP and continued steadily during the steady state which we have called the ATP-form of difference spectrum. At lower temperatures, the ATP-form of difference spectrum decayed into the other form before the steady state was attained. This was identical to the difference spectrum obtained by adding ADP and has been called the ADP-form of difference spectrum. At intermediate temperatures, biphasic decay was observed. The results indicate that the dominant intermediate at the steady state is altered from the one showing the ATP-form of difference spectrum at higher temperatures to that showing the ADP-form at lower temperatures. The population of the two intermediates depends on the temperature between the two extremes. This temperature-induced transition was observed in the presence of any divalent cation such as Mg2+, Mn2+, or Ca2+. A similar transition was observed with the difference spectrum induced by ITP in the presence of MgCl2. The pH dependence of the single early decay of the ATP-induced difference spectrum was measured in the presence of MnCl2 at 1 degree. The apparent rate constant of the decay showed a biphasic pH dependence, having the same shape as the pH activity curve of ATPase [EC 3.6.1.3] observed at higher temperatures. The rate determining step for the steady state ATPase at higher temperatures is thought to be the step of changing from the intermediate complex showing the ATP-form of difference spectrum to that showing the ADP-form. This is inconsistent with our previous mechanism (Yazawa, M. et al. (1973) J. Biochem. 74, 1107-1117). The rate determining step at lower temperatures was assigned as a step of ADP dissociation.", "contents": "Temperature dependence of the decay of the UV absorption difference spectrum of heavy meromyosin induced by adenosine triphosphate and inosine triphosphate. The UV absorption difference spectrum of heavy meromyosin induced by ATP was measured at various temperatures. At higher temperatures, the difference spectrum formed rapidly after adding ATP and continued steadily during the steady state which we have called the ATP-form of difference spectrum. At lower temperatures, the ATP-form of difference spectrum decayed into the other form before the steady state was attained. This was identical to the difference spectrum obtained by adding ADP and has been called the ADP-form of difference spectrum. At intermediate temperatures, biphasic decay was observed. The results indicate that the dominant intermediate at the steady state is altered from the one showing the ATP-form of difference spectrum at higher temperatures to that showing the ADP-form at lower temperatures. The population of the two intermediates depends on the temperature between the two extremes. This temperature-induced transition was observed in the presence of any divalent cation such as Mg2+, Mn2+, or Ca2+. A similar transition was observed with the difference spectrum induced by ITP in the presence of MgCl2. The pH dependence of the single early decay of the ATP-induced difference spectrum was measured in the presence of MnCl2 at 1 degree. The apparent rate constant of the decay showed a biphasic pH dependence, having the same shape as the pH activity curve of ATPase [EC 3.6.1.3] observed at higher temperatures. The rate determining step for the steady state ATPase at higher temperatures is thought to be the step of changing from the intermediate complex showing the ATP-form of difference spectrum to that showing the ADP-form. This is inconsistent with our previous mechanism (Yazawa, M. et al. (1973) J. Biochem. 74, 1107-1117). The rate determining step at lower temperatures was assigned as a step of ADP dissociation."}
{"id": "PMID:14942", "title": "Acceptor activity of subcellular membranes for two terminal sugars, galactose and sialic acid.", "content": "The acceptor activities of subcellular membrane preparations for the terminal sugars, galactose and sialic acid, were compared using a Golgi fraction purified from rat liver as an exogenous emzymes source for sugar transfer. Data are presented which strongly suggest that completion of carbohydrate chains of membrane glycoproteins and glycolipids occurs in the Golgi apparatus. Significant differences of acceptability of galactose and sialic acid were found between plasma membranes of rat liver and hepatoma cells (AH-130), indicating \"incompleteness\" of sugar chains in the latter.", "contents": "Acceptor activity of subcellular membranes for two terminal sugars, galactose and sialic acid. The acceptor activities of subcellular membrane preparations for the terminal sugars, galactose and sialic acid, were compared using a Golgi fraction purified from rat liver as an exogenous emzymes source for sugar transfer. Data are presented which strongly suggest that completion of carbohydrate chains of membrane glycoproteins and glycolipids occurs in the Golgi apparatus. Significant differences of acceptability of galactose and sialic acid were found between plasma membranes of rat liver and hepatoma cells (AH-130), indicating \"incompleteness\" of sugar chains in the latter."}
{"id": "PMID:14943", "title": "A novel and simple colorimetric assay for human serum lipase.", "content": "A new and simple colorimetric method for human serum lipase [EC 3.1.1.3] assay has been developed, using 2,3-dimercaptopropan-1-ol tributyroate as a substrate, 5,5'-dithiobis(2-nitro-benzoic acid) as a chromogenic reagent, phenylmethylsulfonyl fluoride as an inhibitor of serum esterases, and sodium dodecylsulfate as a lipase activator. The method requires only 50 micron1X2 of serum sample and a reaction time of less than 30 min. The method is reproducible and sensitive enough to measure low levels of lipase activity in normal and abnormal sera. The gel filtration of serum samples on a Sephadex G-200 column gave one peak of lipase activity, when measured by the present method, and the molecular weight of the enzyme was identical with that of lipase of human pancreatic origin, confirming the specificity of this new method for the serum lipase.", "contents": "A novel and simple colorimetric assay for human serum lipase. A new and simple colorimetric method for human serum lipase [EC 3.1.1.3] assay has been developed, using 2,3-dimercaptopropan-1-ol tributyroate as a substrate, 5,5'-dithiobis(2-nitro-benzoic acid) as a chromogenic reagent, phenylmethylsulfonyl fluoride as an inhibitor of serum esterases, and sodium dodecylsulfate as a lipase activator. The method requires only 50 micron1X2 of serum sample and a reaction time of less than 30 min. The method is reproducible and sensitive enough to measure low levels of lipase activity in normal and abnormal sera. The gel filtration of serum samples on a Sephadex G-200 column gave one peak of lipase activity, when measured by the present method, and the molecular weight of the enzyme was identical with that of lipase of human pancreatic origin, confirming the specificity of this new method for the serum lipase."}
{"id": "PMID:14944", "title": "Nucleoside triphosphate phosphohydrolase associated with cytoplasmic polyhedrosis virus.", "content": "Nucleoside triphosphate phosphohydrolase [EC 3.6.1.15] activity was found to be included in silkworm cytoplasmic polyhedrosis (CP) virus, which synthesizes mRNA carrying the 5'-terminal modification. This enzyme releases orthophosphate from the gamma-position in a nucleoside triphosphate, leaving nucleoside diphosphate. The rate of hydrolysis of ATP is faster than that of any other ribonucleoside triphosphate. Deoxy ATP is hydrolyzed rather faster than ATP. However, polynucleotides carrying triphosphate at the 5'-terminus, that is, 4S RNA which was synthesized by E. coli RNA polymerase [EC 2.7.7.6] using calf thymus DNA as a template, and the phage Q beta RNA (30S), are not effective substrates for this enzyme. Although the CP virion loses the viral genome and one kind of protein component on proteolytic treatment with pronase, the partially degraded virion still retains phosphohydrolase activity. The phosphohydrolase must therefore be associated firmly with the virion. This enzyme does not require the presence of nucleic acid for its function. Phosphohydrolysis of ATP by this enzyme activity represents a first step in the synthesis of the 5'-terminal modified mRNA of CP virus.", "contents": "Nucleoside triphosphate phosphohydrolase associated with cytoplasmic polyhedrosis virus. Nucleoside triphosphate phosphohydrolase [EC 3.6.1.15] activity was found to be included in silkworm cytoplasmic polyhedrosis (CP) virus, which synthesizes mRNA carrying the 5'-terminal modification. This enzyme releases orthophosphate from the gamma-position in a nucleoside triphosphate, leaving nucleoside diphosphate. The rate of hydrolysis of ATP is faster than that of any other ribonucleoside triphosphate. Deoxy ATP is hydrolyzed rather faster than ATP. However, polynucleotides carrying triphosphate at the 5'-terminus, that is, 4S RNA which was synthesized by E. coli RNA polymerase [EC 2.7.7.6] using calf thymus DNA as a template, and the phage Q beta RNA (30S), are not effective substrates for this enzyme. Although the CP virion loses the viral genome and one kind of protein component on proteolytic treatment with pronase, the partially degraded virion still retains phosphohydrolase activity. The phosphohydrolase must therefore be associated firmly with the virion. This enzyme does not require the presence of nucleic acid for its function. Phosphohydrolysis of ATP by this enzyme activity represents a first step in the synthesis of the 5'-terminal modified mRNA of CP virus."}
{"id": "PMID:14945", "title": "Effects of polyamines on the degradation of ribonucleic acids by polynucleotide phosphorylase of Micrococcus luteus.", "content": "The effects of polyamines on the breakdown of synthetic polynucleotides [poly(A), poly(C), and poly(U)] by polynucleotide phosphorylase [polyribonucleotide: orthophosphate nucleotidyltransferase, EC 2.7.7.8] from Micrococcus luteus have been studied. Although the breakdown of all the synthetic polynucleotides tested was stimulated by polyamines, the degree of stimulation by polyamines was in the order poly(C) greater than poly(A) greater than poly(U) at pH 7.5. However, the difference in degree of stimulation among polynucleotides decreased as the pH or monovalent cation concentration was increased. In the presence of heparin, an inhibitor of polynucleotide phosphorylase hydrolysis of polynucleotides, spermidine clearly stimulated the breakdown of poly(C) and poly(A), while the breakdown of poly(U) was stimulated only slightly by the addition of spermidine. Although binding of [14C]spermine to polynucleotide phosphorylase was observed by gel filtration, the amount of spermine bound to the enzyme was much less than that to RNA.", "contents": "Effects of polyamines on the degradation of ribonucleic acids by polynucleotide phosphorylase of Micrococcus luteus. The effects of polyamines on the breakdown of synthetic polynucleotides [poly(A), poly(C), and poly(U)] by polynucleotide phosphorylase [polyribonucleotide: orthophosphate nucleotidyltransferase, EC 2.7.7.8] from Micrococcus luteus have been studied. Although the breakdown of all the synthetic polynucleotides tested was stimulated by polyamines, the degree of stimulation by polyamines was in the order poly(C) greater than poly(A) greater than poly(U) at pH 7.5. However, the difference in degree of stimulation among polynucleotides decreased as the pH or monovalent cation concentration was increased. In the presence of heparin, an inhibitor of polynucleotide phosphorylase hydrolysis of polynucleotides, spermidine clearly stimulated the breakdown of poly(C) and poly(A), while the breakdown of poly(U) was stimulated only slightly by the addition of spermidine. Although binding of [14C]spermine to polynucleotide phosphorylase was observed by gel filtration, the amount of spermine bound to the enzyme was much less than that to RNA."}
{"id": "PMID:14946", "title": "The reactions of phenylglyoxal and related reagents with amino acids.", "content": "1. The reaction of phenylglyoxal (PGO), glyoxal (GO), and methylglyoxal (MGO) with amino acids were investigated at mild pH values at 25 degrees. These aldehydes reacted most rapidly with arginine and the rate of reaction increased with increasing pH values. Histidine, cystine, glycine, tryptophan, asparagine, glutamine, and lysine reacted with these aldehydes at significant but various rates, depending on the pH and the kind of the reagent used. The reactions with these amino acids seemed to involve both the alpha-amino groups and the side chain groups, and no significant reaction appeared to occur with the side chain alone except with those of arginine, lysine, and cysteine. These reagents were similarly reactive with the guanidinium group of arginine, but PGO appeared to be much less reactive with the epsilone-amino group of lysine than MGO and GO. The other ordinary amino acids were very much less reactive or did not react at all with these reagents, with the exception of cysteine. 2. Di-PGO-L-arginine was prepared from Nalpha-benzyloxycarbonyl-L-arginine, and di-PGO-methylguanidine from methylguanidine, and the stoichiometry of the reaction of two PGO molecules with one guanidino group was confirmed. A glyoxal derivative of L-arginine (GO-arginine) was prepared by reaction of glyoxal with arginine. GO-arginine was fairly unstable, especially at higher pH values. A similar derivative (MGO-arginine) was also found to be formed by reaction of MGO with L-arginine, and was similarly unstable. These derivatives, however, did not regenerate arginine upon acid hydrolysis.", "contents": "The reactions of phenylglyoxal and related reagents with amino acids. 1. The reaction of phenylglyoxal (PGO), glyoxal (GO), and methylglyoxal (MGO) with amino acids were investigated at mild pH values at 25 degrees. These aldehydes reacted most rapidly with arginine and the rate of reaction increased with increasing pH values. Histidine, cystine, glycine, tryptophan, asparagine, glutamine, and lysine reacted with these aldehydes at significant but various rates, depending on the pH and the kind of the reagent used. The reactions with these amino acids seemed to involve both the alpha-amino groups and the side chain groups, and no significant reaction appeared to occur with the side chain alone except with those of arginine, lysine, and cysteine. These reagents were similarly reactive with the guanidinium group of arginine, but PGO appeared to be much less reactive with the epsilone-amino group of lysine than MGO and GO. The other ordinary amino acids were very much less reactive or did not react at all with these reagents, with the exception of cysteine. 2. Di-PGO-L-arginine was prepared from Nalpha-benzyloxycarbonyl-L-arginine, and di-PGO-methylguanidine from methylguanidine, and the stoichiometry of the reaction of two PGO molecules with one guanidino group was confirmed. A glyoxal derivative of L-arginine (GO-arginine) was prepared by reaction of glyoxal with arginine. GO-arginine was fairly unstable, especially at higher pH values. A similar derivative (MGO-arginine) was also found to be formed by reaction of MGO with L-arginine, and was similarly unstable. These derivatives, however, did not regenerate arginine upon acid hydrolysis."}
{"id": "PMID:14947", "title": "The structure and function of acid proteases. VII. Distribution and some properties of acid proteases in monkey tissues.", "content": "1. The distribution of acid protease activity in various tissues of Japanese monkey (Macaca fuscata fuscata) was investigated with hemoglobin as a substrate at pH 3.0. The activity per protein weight in crude extracts was highest in spleen and lung, and decreased in the order: spleen, lung greater than kidney, testis greater than brain greater than liver, placenta greater than thyroid gland, muscle. The activity in crude muscle extract was about one-tenth those of spleen and lung. The activity per wet tissue weight was in roughly the same order except for a lower activity per wet weight of brain. 2. Upon chromatography of each crude extract on a Sephadex G-100 column, one major activity peak was eluted at a position corresponding to a molecular weight of about 41,000. This enzyme activity is attributed to cathepsin D [EC 3.4.23.5]. In addition, a minor activity peak was eluted in the case of spleen, lung and kidney at the break-through position, corresponding to a molecular weight of more than 100,000. This activity peak is presumably due to cathepsin E. These acid protease activities were, in most cases, strongly inhibited by pepstatin, an acid protease-specific peptide inhibitor. 3. The distribution of acid protease activity was investigated in the brain of crab-eating monkey (Macaca fascicularis). The activity was fairly evenly distributed among several regions of the brain, and its distribution was similar to those of other acid hydrolases, especially N-acetyl-beta-D-glucosaminidase [EC 3.2.1.30] and acid phosphatase [EC 3.1.3.2], which are marker enzymes of lysosomes.", "contents": "The structure and function of acid proteases. VII. Distribution and some properties of acid proteases in monkey tissues. 1. The distribution of acid protease activity in various tissues of Japanese monkey (Macaca fuscata fuscata) was investigated with hemoglobin as a substrate at pH 3.0. The activity per protein weight in crude extracts was highest in spleen and lung, and decreased in the order: spleen, lung greater than kidney, testis greater than brain greater than liver, placenta greater than thyroid gland, muscle. The activity in crude muscle extract was about one-tenth those of spleen and lung. The activity per wet tissue weight was in roughly the same order except for a lower activity per wet weight of brain. 2. Upon chromatography of each crude extract on a Sephadex G-100 column, one major activity peak was eluted at a position corresponding to a molecular weight of about 41,000. This enzyme activity is attributed to cathepsin D [EC 3.4.23.5]. In addition, a minor activity peak was eluted in the case of spleen, lung and kidney at the break-through position, corresponding to a molecular weight of more than 100,000. This activity peak is presumably due to cathepsin E. These acid protease activities were, in most cases, strongly inhibited by pepstatin, an acid protease-specific peptide inhibitor. 3. The distribution of acid protease activity was investigated in the brain of crab-eating monkey (Macaca fascicularis). The activity was fairly evenly distributed among several regions of the brain, and its distribution was similar to those of other acid hydrolases, especially N-acetyl-beta-D-glucosaminidase [EC 3.2.1.30] and acid phosphatase [EC 3.1.3.2], which are marker enzymes of lysosomes."}
{"id": "PMID:14948", "title": "Studies on the heterotropic interaction of hemoglobin. I. Mass spectrometric method for determination of the pKa of the beta-146 histidine residue in human hemoglobin.", "content": "A mass spectrometric method was developed to determine pH-dependent hydrogen-deuterium exchange at the C-2 position of the imidazole ring of histidine, after converting the amino acid to the methylthiohydantoin derivative. The amount of deuterium exchange in N-acetyl-histidine estimated by the present method was confirmed to be in good agreement with that determined by NMR spectrometry. N-Acetylhistidine was deuterated at various pH's. From the amount of deuterium exchange, a pseudo-first order rate constant (kpsi) was calculated. A pKa value of 7.2 for the amino acid was obtained from the relation between kpsi and pH. This method was applied to estimate the pKa value of beta-146 histidine in human hemoglobin. Human hemoglobin deuterated at various pH's was digested with carboxypeptidase A [EC 3.4.12.2] to release the beta-146 histidine. The amount of deuterium exchange in the isolated histidine was determined to obtain kpsi. From these measurements pKa values of 7.0 for the histidine in oxyhemoglobin and of 8.2 for that in deoxyhemoglobin were found at 36.5 degrees, respectively.", "contents": "Studies on the heterotropic interaction of hemoglobin. I. Mass spectrometric method for determination of the pKa of the beta-146 histidine residue in human hemoglobin. A mass spectrometric method was developed to determine pH-dependent hydrogen-deuterium exchange at the C-2 position of the imidazole ring of histidine, after converting the amino acid to the methylthiohydantoin derivative. The amount of deuterium exchange in N-acetyl-histidine estimated by the present method was confirmed to be in good agreement with that determined by NMR spectrometry. N-Acetylhistidine was deuterated at various pH's. From the amount of deuterium exchange, a pseudo-first order rate constant (kpsi) was calculated. A pKa value of 7.2 for the amino acid was obtained from the relation between kpsi and pH. This method was applied to estimate the pKa value of beta-146 histidine in human hemoglobin. Human hemoglobin deuterated at various pH's was digested with carboxypeptidase A [EC 3.4.12.2] to release the beta-146 histidine. The amount of deuterium exchange in the isolated histidine was determined to obtain kpsi. From these measurements pKa values of 7.0 for the histidine in oxyhemoglobin and of 8.2 for that in deoxyhemoglobin were found at 36.5 degrees, respectively."}
{"id": "PMID:14949", "title": "Glutamate dehydrogenase from Bacillus subtilis PCI 219. I. Purification and properties.", "content": "Bacillus subtilis PCI 219 has a single glutamate dehydrogenase (GDH) [EC 1.4.1.3] with dual coenzyme specificity [for NAD(H) and NADP(H)]. The enzyme was purified 800-fold from crude extracts of B. subtilis from the post-exponential phase of growth and showed one significant protein band on gel electrophoresis. This band was determined, by activity staining, to have all the GDH nucleotide specificities. Its molecular weight was estimated to be 250,000+/-20,000 by gel filtration, and 270,000+/-30,000 by zone centrifugation in a sucrose density gradient. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that GDH has a subunit size of about 57,000. The pI of GDH was found to bepH 3.7 by isoelectric focusing. GDH exhibited nonlinear kinetics in the reduction of NAD+, and in the reverse direction, the substrate, NH4+, was strongly inhibitory at high concentrations. Purine nucleotides did not affect the activity. The oxidative demination of glutamate was significantly inhibited by the metabolites oxaloacetate and citrate, which acted as allosteric effectors of this enzyme,inhibiting the reaction in one direction. The pH optimum of each of the activities of GDH and the stability of GDH are also reported.", "contents": "Glutamate dehydrogenase from Bacillus subtilis PCI 219. I. Purification and properties. Bacillus subtilis PCI 219 has a single glutamate dehydrogenase (GDH) [EC 1.4.1.3] with dual coenzyme specificity [for NAD(H) and NADP(H)]. The enzyme was purified 800-fold from crude extracts of B. subtilis from the post-exponential phase of growth and showed one significant protein band on gel electrophoresis. This band was determined, by activity staining, to have all the GDH nucleotide specificities. Its molecular weight was estimated to be 250,000+/-20,000 by gel filtration, and 270,000+/-30,000 by zone centrifugation in a sucrose density gradient. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that GDH has a subunit size of about 57,000. The pI of GDH was found to bepH 3.7 by isoelectric focusing. GDH exhibited nonlinear kinetics in the reduction of NAD+, and in the reverse direction, the substrate, NH4+, was strongly inhibitory at high concentrations. Purine nucleotides did not affect the activity. The oxidative demination of glutamate was significantly inhibited by the metabolites oxaloacetate and citrate, which acted as allosteric effectors of this enzyme,inhibiting the reaction in one direction. The pH optimum of each of the activities of GDH and the stability of GDH are also reported."}
{"id": "PMID:14950", "title": "Purificantion and characterization of inorganic pyrophosphatase from Thiobacillus thiooxidans.", "content": "An inorganic pyrophosphatase [EC 3.6.1.1] was isolated from Thiobacillus thiooxidans and purified 975-fold to a state of apparent homogeneity. The enzyme catalyzed the hydrolysis of inorganic pyrophosphate and no activity was found with a variety of other phosphate esters. The cation Mg2+ was required for maximum activity; Co2+ and Mn2+ supported 25 per cent and 10.6 per cent of the activity with Mg2+, respectively. The pH optimum was 8.8. The molecular weight was estimated to be 88,000 by gel filtration and SDS gel electrophoresis, and the enzyme consisted of four identical subunits. The isoelectric point was found to be 5.05. The enzyme was exceptionally heat-stable in the presence of 0.01 M Mg2+.", "contents": "Purificantion and characterization of inorganic pyrophosphatase from Thiobacillus thiooxidans. An inorganic pyrophosphatase [EC 3.6.1.1] was isolated from Thiobacillus thiooxidans and purified 975-fold to a state of apparent homogeneity. The enzyme catalyzed the hydrolysis of inorganic pyrophosphate and no activity was found with a variety of other phosphate esters. The cation Mg2+ was required for maximum activity; Co2+ and Mn2+ supported 25 per cent and 10.6 per cent of the activity with Mg2+, respectively. The pH optimum was 8.8. The molecular weight was estimated to be 88,000 by gel filtration and SDS gel electrophoresis, and the enzyme consisted of four identical subunits. The isoelectric point was found to be 5.05. The enzyme was exceptionally heat-stable in the presence of 0.01 M Mg2+."}
{"id": "PMID:14951", "title": "Purification of hyaluronidase from human placenta.", "content": "Hyaluronidase [EC 3.2.1.35] was isolated from human placenta and purified by ammonium sulfate fractionation, DEAE-cellulose column chromatography and gel filtration on Sephadex G-150. Its isoelectric point was at pH 5.2 and the molecular weight was 7 X 10(4) based on Sephadex G-200 gel filtration data. This enzyme was very stable at temperatures below 30 degree, but was almost completely inactivated at 60degree within 30 min. Its optimum pH was 3.9, a characteristic property of a lysosomal hyaluronidase. The Michaelis constant was 1.18 x 10(-1) mg per ml with purified hyaluronate. This enzyme depolymerized hyaluronate, chondroitin, chondroitin 4-sulfate and 6-sulfate, and the end product formed from hyaluronate was tetrasaccharide. Its biological diffusing activity was statistically significant on intracutaneous injection of 1.86 mU of the hyaluronidase into the back skine of a rabbit.", "contents": "Purification of hyaluronidase from human placenta. Hyaluronidase [EC 3.2.1.35] was isolated from human placenta and purified by ammonium sulfate fractionation, DEAE-cellulose column chromatography and gel filtration on Sephadex G-150. Its isoelectric point was at pH 5.2 and the molecular weight was 7 X 10(4) based on Sephadex G-200 gel filtration data. This enzyme was very stable at temperatures below 30 degree, but was almost completely inactivated at 60degree within 30 min. Its optimum pH was 3.9, a characteristic property of a lysosomal hyaluronidase. The Michaelis constant was 1.18 x 10(-1) mg per ml with purified hyaluronate. This enzyme depolymerized hyaluronate, chondroitin, chondroitin 4-sulfate and 6-sulfate, and the end product formed from hyaluronate was tetrasaccharide. Its biological diffusing activity was statistically significant on intracutaneous injection of 1.86 mU of the hyaluronidase into the back skine of a rabbit."}
{"id": "PMID:14952", "title": "Reaction of chlorocruorin with heme iron ligands and carbonyl reagents.", "content": "Chlorocruorin was purified from Potamilla leptochaeta and the spectral properties of its derivatives wwere investigated. Ferri- or ferrochlorocruorin did not exhibits a ferrihemochrome or ferrohemochrome spectrum, respectively. Oxy- and carbonmonoxy-ferrochlorocruorin did show ferrohemochrome-type spectra. Ferrihemochromes were formed, however, when oxy-or ferrichlorocruorin was treated with 0.02-0.05% SDS, and they were transformed to ferrohemochromes by reduction with sodium dithionite. Ferrihemochrome formation was also brought about by increasing the pH of a ferrichlorocruorin solution to 9, or by liganding of extrinsic imidazole or cyanide to the ferric pigment. Therefore, it is apparent that at least one of the coordination positions on the heme iron in ferri-and ferrochlorocruorin is vacant or occupied by a weak-field ligand. Titration studies of ferrichlorocruorin with imidazole indicated that this supposedly vacant coordination position was occupied first by the imidazole, and that the intrinsic ligand of protein orgin was replaced finally at higher concentrations. The extrinsic ligands in the cyanide and imidazole complexes of ferrichlorocruorin were excluded from their coordination positions as the protein moiety assumed conformations inherent to the reduced pigment. Spectral analyses indicated that the intrinsic ligand is an imidazole moiety of a histidyl residue. When chlorocruorin was intact, carbonyl reagents such as cyanide and sodium bisulfite did not add to the formyl group of chlorocruoreheme. When the protein conformation was perturbed by SDS, addition to ferrichlorocruorin occurred appreciably. This addition was accelerated if the heme iron coordination position had been occupied by strong field ligands,and was reversed to some extent as the chlorocruorin complexes were reduced.", "contents": "Reaction of chlorocruorin with heme iron ligands and carbonyl reagents. Chlorocruorin was purified from Potamilla leptochaeta and the spectral properties of its derivatives wwere investigated. Ferri- or ferrochlorocruorin did not exhibits a ferrihemochrome or ferrohemochrome spectrum, respectively. Oxy- and carbonmonoxy-ferrochlorocruorin did show ferrohemochrome-type spectra. Ferrihemochromes were formed, however, when oxy-or ferrichlorocruorin was treated with 0.02-0.05% SDS, and they were transformed to ferrohemochromes by reduction with sodium dithionite. Ferrihemochrome formation was also brought about by increasing the pH of a ferrichlorocruorin solution to 9, or by liganding of extrinsic imidazole or cyanide to the ferric pigment. Therefore, it is apparent that at least one of the coordination positions on the heme iron in ferri-and ferrochlorocruorin is vacant or occupied by a weak-field ligand. Titration studies of ferrichlorocruorin with imidazole indicated that this supposedly vacant coordination position was occupied first by the imidazole, and that the intrinsic ligand of protein orgin was replaced finally at higher concentrations. The extrinsic ligands in the cyanide and imidazole complexes of ferrichlorocruorin were excluded from their coordination positions as the protein moiety assumed conformations inherent to the reduced pigment. Spectral analyses indicated that the intrinsic ligand is an imidazole moiety of a histidyl residue. When chlorocruorin was intact, carbonyl reagents such as cyanide and sodium bisulfite did not add to the formyl group of chlorocruoreheme. When the protein conformation was perturbed by SDS, addition to ferrichlorocruorin occurred appreciably. This addition was accelerated if the heme iron coordination position had been occupied by strong field ligands,and was reversed to some extent as the chlorocruorin complexes were reduced."}
{"id": "PMID:14953", "title": "Molecular architecture of cytochrome oxidase and its transition on treatment with alkali or sodium dodecyl sulfate.", "content": "In dimeric cytochrome oxidase [EC 1.9.3.1], one of the two heme a molecules of one monomeric unit has been proposed to be converted by the other unit, thus becoming latent in terms of catalytic functions (1). As the dimer was split into two monomers by treatment with alkali or sodium dodecyl sulfate (SDS), it was shown that the intensity of circular dichroism (CD) in the Soret region due to heme a decreased, probably reflecting release of the strain on the latent heme. On the other hand, the profile of magnetic circular dichroism (MCD) was nearly unchanged during this conversion, except for a weakening of the signal due to deprotonation of the heme during the alkali treatment. When the monomer was further dissociated into constituent subunits in strong alkali or at high concentrations of SDS, the CD spectrum disappeared almost completely, indicating loss of the asymmetric interactions of the chromophoric heme a with its immediate environments, consisting of the subunit assembly. The MCD pattern also suffered a small change as the dissociation proceeded, and a specific pattern appeared as the Schiff base was finally formed. The Schiff base formation of cytochrome oxidase in strong alkali proceeded in two steps whether the heme iron was in the oxidized or reduced state. As a consequence of the initial rapid reaction, the enzyme was suggested to have been disintegrated into constituent subunits with heme a being attached nonspecifically to either one, and structural characteristics dependent on the redox state were completely lost. The Arrehenius plot for this rapid change showed a break, indicating a transition in the structure of the cytochrome oxidase assembly, although no such phenomenon was observed during the slow reaction. Activation parameters in the rapid and slow reactions for the oxidized and reduced oxidase are given. Based on these findings, as well as other considerations, a molecular architecture of this enzyme is proposed; the role of heme a in anchoring four 14,000-dalton polypeptides into the minimal functional unit catalyzing the aerobic oxidation of ferrocytochrome c is emphasized.", "contents": "Molecular architecture of cytochrome oxidase and its transition on treatment with alkali or sodium dodecyl sulfate. In dimeric cytochrome oxidase [EC 1.9.3.1], one of the two heme a molecules of one monomeric unit has been proposed to be converted by the other unit, thus becoming latent in terms of catalytic functions (1). As the dimer was split into two monomers by treatment with alkali or sodium dodecyl sulfate (SDS), it was shown that the intensity of circular dichroism (CD) in the Soret region due to heme a decreased, probably reflecting release of the strain on the latent heme. On the other hand, the profile of magnetic circular dichroism (MCD) was nearly unchanged during this conversion, except for a weakening of the signal due to deprotonation of the heme during the alkali treatment. When the monomer was further dissociated into constituent subunits in strong alkali or at high concentrations of SDS, the CD spectrum disappeared almost completely, indicating loss of the asymmetric interactions of the chromophoric heme a with its immediate environments, consisting of the subunit assembly. The MCD pattern also suffered a small change as the dissociation proceeded, and a specific pattern appeared as the Schiff base was finally formed. The Schiff base formation of cytochrome oxidase in strong alkali proceeded in two steps whether the heme iron was in the oxidized or reduced state. As a consequence of the initial rapid reaction, the enzyme was suggested to have been disintegrated into constituent subunits with heme a being attached nonspecifically to either one, and structural characteristics dependent on the redox state were completely lost. The Arrehenius plot for this rapid change showed a break, indicating a transition in the structure of the cytochrome oxidase assembly, although no such phenomenon was observed during the slow reaction. Activation parameters in the rapid and slow reactions for the oxidized and reduced oxidase are given. Based on these findings, as well as other considerations, a molecular architecture of this enzyme is proposed; the role of heme a in anchoring four 14,000-dalton polypeptides into the minimal functional unit catalyzing the aerobic oxidation of ferrocytochrome c is emphasized."}
{"id": "PMID:14954", "title": "Reconstitution of vesicles capable of energy transformation from phospholipids and adenosine triphosphatase of a thermophilic bacterium.", "content": "1. A stable ATPase [EC 3.6.1.3] complex (TF0-F1) from the thermophilic bacterium PS3 was reconstituted into vesicles capable of energy transformation,measured as ATP-dependent enhancement of fluorescence of 8-anilinonoaphthalene-1-sulfonate. 2. The factors necessary for obtaining highly active vesicles were investigated. Cholate and deoxycholate were both required for solubilization of TF0-F1 and P-lipids, and removal of the detergents by dialysis resulted in vesicle formation. Medium of around pH 8 and low ionic strength containing 2.5 mM MgSO4 was found suitable for dialysis. The optimal temperature for reconstitution was 30 degrees with soybean P-lipids and 45 degree with PS3 P-lipids. The optimal ratio of protein to lipid was about 1/50. 3. The vesicles obtained under these conditions were mainly 100-200 nm in diameter, covered with 9.5 nm spheres, and had a bouyant density of 1.06 in sucrose andan internal volume of about 0.5 mul per mg of P-lipids.", "contents": "Reconstitution of vesicles capable of energy transformation from phospholipids and adenosine triphosphatase of a thermophilic bacterium. 1. A stable ATPase [EC 3.6.1.3] complex (TF0-F1) from the thermophilic bacterium PS3 was reconstituted into vesicles capable of energy transformation,measured as ATP-dependent enhancement of fluorescence of 8-anilinonoaphthalene-1-sulfonate. 2. The factors necessary for obtaining highly active vesicles were investigated. Cholate and deoxycholate were both required for solubilization of TF0-F1 and P-lipids, and removal of the detergents by dialysis resulted in vesicle formation. Medium of around pH 8 and low ionic strength containing 2.5 mM MgSO4 was found suitable for dialysis. The optimal temperature for reconstitution was 30 degrees with soybean P-lipids and 45 degree with PS3 P-lipids. The optimal ratio of protein to lipid was about 1/50. 3. The vesicles obtained under these conditions were mainly 100-200 nm in diameter, covered with 9.5 nm spheres, and had a bouyant density of 1.06 in sucrose andan internal volume of about 0.5 mul per mg of P-lipids."}
{"id": "PMID:14955", "title": "Proteases from purulent sputum. Purification and properties of the elastase and chymotrypsin-like enzymes.", "content": "A procedure is described for the purification of the elastase and chymotrypsin-like enzymes from purulent sputum. This procedure permitted the isolation of 132 mg and 120 mg of the elastase and chymotrypsin-like enzymes, respectively, from 230 g of purulent sputum. The elastase enzymes consist of a family of five isozymes, and at least three isozymes comprise the chymotrypsin-like enzyme system. The elastases proved to be immunologically identical with the corresponding enzyme of human leukocytes. These enzymes were characterized with respect to molecular weight, amino acid and carbohydrate composition, several kinetic parameters, and inhibition by various synthetic and natural inhibitors. The properties so found were comparable to those which had been previously reported by others for the elastase and chymotrypsin-like enzymes isolated directly from leukocytic granules.", "contents": "Proteases from purulent sputum. Purification and properties of the elastase and chymotrypsin-like enzymes. A procedure is described for the purification of the elastase and chymotrypsin-like enzymes from purulent sputum. This procedure permitted the isolation of 132 mg and 120 mg of the elastase and chymotrypsin-like enzymes, respectively, from 230 g of purulent sputum. The elastase enzymes consist of a family of five isozymes, and at least three isozymes comprise the chymotrypsin-like enzyme system. The elastases proved to be immunologically identical with the corresponding enzyme of human leukocytes. These enzymes were characterized with respect to molecular weight, amino acid and carbohydrate composition, several kinetic parameters, and inhibition by various synthetic and natural inhibitors. The properties so found were comparable to those which had been previously reported by others for the elastase and chymotrypsin-like enzymes isolated directly from leukocytic granules."}
{"id": "PMID:14956", "title": "Tryptic cleavage of rat liver sulfite oxidase. Isolation and characterization of molybdenum and heme domains.", "content": "Treatment of rat liver sulfite oxidase with trypsin leads to loss of ability to oxidize sulfite in the presence of cytochrome c as electron acceptor. Ability to oxidize sulfite with ferricyanide as acceptor is undiminished, while sulfite leads to O2 activity is partially retained. Gel filtration of the proteolytic products has led to the isolation of two major fragments of dissimilar size derived from sulfite oxidase. The smaller fragment has a molecular weight of 9500 and appears to be monomeric when detached from sulfite oxidase. It contains the heme in its cytochrome b5 structure, has no sulfite oxidase activity, and is reducible with dithionite but not with sulfite. The heme fragment can mediate electron transfer between pig liver microsomal NADH cytochrome b5 reductase and cytochrome c. The larger fragment has a molecular weight of 47,400 under denaturing conditions but elutes from Sephadex G-200 as a dimer. It contains no heme but retains all of the molybdenum and the modified sulfite-oxidizing capacity present in the proteolytic mixture. All of the EPR properties of the molybdenum center of native sulfite oxidase are retained in the molybdenum fragment. The molybdenum center is a weak chromophore with an absorption sectrum suggestive of coordination with sulfur ligands. Reduction by sulfite generates a spectrum attributable to molybdenum (V). Spectra of oxidized and sulfite-reduced preparations are sensitive to anions and pH. NH2-terminal analysis of native sulfite oxidase and the two tryptic fragments has permitted the conclusion that the sequence represented by the heme fragment is the NH2 terminus of native enzyme. These studies have demonstrated that the two cofactor moieties of sulfite oxidase are contained in distinct domains which are covalently held in contiguity by means of an exposed hinge region. Isolation of functional heme and molybdenum domains of sulfite oxidase after tryptic cleavage has demonstrated conclusively that the cytochrome b5 region of the molecule is required for electron transfer to the physiological acceptor, cytochrome c.", "contents": "Tryptic cleavage of rat liver sulfite oxidase. Isolation and characterization of molybdenum and heme domains. Treatment of rat liver sulfite oxidase with trypsin leads to loss of ability to oxidize sulfite in the presence of cytochrome c as electron acceptor. Ability to oxidize sulfite with ferricyanide as acceptor is undiminished, while sulfite leads to O2 activity is partially retained. Gel filtration of the proteolytic products has led to the isolation of two major fragments of dissimilar size derived from sulfite oxidase. The smaller fragment has a molecular weight of 9500 and appears to be monomeric when detached from sulfite oxidase. It contains the heme in its cytochrome b5 structure, has no sulfite oxidase activity, and is reducible with dithionite but not with sulfite. The heme fragment can mediate electron transfer between pig liver microsomal NADH cytochrome b5 reductase and cytochrome c. The larger fragment has a molecular weight of 47,400 under denaturing conditions but elutes from Sephadex G-200 as a dimer. It contains no heme but retains all of the molybdenum and the modified sulfite-oxidizing capacity present in the proteolytic mixture. All of the EPR properties of the molybdenum center of native sulfite oxidase are retained in the molybdenum fragment. The molybdenum center is a weak chromophore with an absorption sectrum suggestive of coordination with sulfur ligands. Reduction by sulfite generates a spectrum attributable to molybdenum (V). Spectra of oxidized and sulfite-reduced preparations are sensitive to anions and pH. NH2-terminal analysis of native sulfite oxidase and the two tryptic fragments has permitted the conclusion that the sequence represented by the heme fragment is the NH2 terminus of native enzyme. These studies have demonstrated that the two cofactor moieties of sulfite oxidase are contained in distinct domains which are covalently held in contiguity by means of an exposed hinge region. Isolation of functional heme and molybdenum domains of sulfite oxidase after tryptic cleavage has demonstrated conclusively that the cytochrome b5 region of the molecule is required for electron transfer to the physiological acceptor, cytochrome c."}
{"id": "PMID:14957", "title": "Asparagine transaminase from rat liver.", "content": "Asparagine transaminase has been purified about 200-fold from rat liver. The enzyme has a broad specificity toward both amino acids and alpha-keto acids. Thus, amino acids substituted in the beta position such as asparagine, S-methylcysteine, phenylalanine, cysteine, serine, and aspartate are substrates. The enzyme is also active with alanine, methionine, homoserine, alpha-aminobutyrate, glutamine, and leucine. The enzyme has a high affinity for glyoxylate but the affinity falls off markedly through the series glyoxylate, pyruvate, alpha-ketoburyrate, alpha-Keto acids substituted in the beta or gamma position, such as alpha-ketosuccinamate, phenylpyruvate, p-hydroxyphenylpyruvate, alpha-keto-gamma-methiolburyrate, and alpha-keto-gamma-hydroxybutyrate, are substrates for the enzyme. Amino acids or alpha-keto acids possessing a branch point at the beta carbon are inactive. Kinetic analysis of the asparagine glyoxylate transamination reaction is consistent with a ping-pong mechanism.", "contents": "Asparagine transaminase from rat liver. Asparagine transaminase has been purified about 200-fold from rat liver. The enzyme has a broad specificity toward both amino acids and alpha-keto acids. Thus, amino acids substituted in the beta position such as asparagine, S-methylcysteine, phenylalanine, cysteine, serine, and aspartate are substrates. The enzyme is also active with alanine, methionine, homoserine, alpha-aminobutyrate, glutamine, and leucine. The enzyme has a high affinity for glyoxylate but the affinity falls off markedly through the series glyoxylate, pyruvate, alpha-ketoburyrate, alpha-Keto acids substituted in the beta or gamma position, such as alpha-ketosuccinamate, phenylpyruvate, p-hydroxyphenylpyruvate, alpha-keto-gamma-methiolburyrate, and alpha-keto-gamma-hydroxybutyrate, are substrates for the enzyme. Amino acids or alpha-keto acids possessing a branch point at the beta carbon are inactive. Kinetic analysis of the asparagine glyoxylate transamination reaction is consistent with a ping-pong mechanism."}
{"id": "PMID:14958", "title": "Quantitative determination of carbamino adducts of alpha and beta chains in human adult hemoglobin in presence and absence of carbon monoxide and 2,3-diphosphoglycerate.", "content": "The principal component of normal adult human hemoglobin was equilibrated under various conditions with 13CO2. Quantitative analysis of the carbamino resonance intensities over the pH range of 6.5 to 9.0 shows that the effects of conversion from the deoxy to the liganded state in reducing the carbamino adduct formation occur predominantly at Val-1beta. Analysis of the pH dependence of carbamino formation at constant total carbonates yields values of pKz and pKc for Val-1beta and Val-1alpha in the deoxy and liganded conditions. In contrast to the Val-1beta as the allosteric site for CO2, the Val-1alpha site is shown to be primarily an alkaline Bohr group. 2,3-Diphosphoglycerate is shown to reduce substantially the Val-1beta carbamino resonance intensity in deoxyhemoglobin. Evidence for 2,3-diphosphoglycerate effects in carbon monoxide hemoglobin at both Val-1alpha and Val-1beta sites is presented. Enhanced carbamino formation in carbon monoxide hemoglobin at Val-1beta is observed at pH values less than 7.8. Finally, chemical exchange analysis of the spectra shows the release rate of the deoxy Val-1alpha carbamino adduct to be greater than that for deoxy Val-1beta. At pH 7.47 k-1obs,beta congruent to 1.0 and k-1obs, alpha congruent to 11.0 s-1.", "contents": "Quantitative determination of carbamino adducts of alpha and beta chains in human adult hemoglobin in presence and absence of carbon monoxide and 2,3-diphosphoglycerate. The principal component of normal adult human hemoglobin was equilibrated under various conditions with 13CO2. Quantitative analysis of the carbamino resonance intensities over the pH range of 6.5 to 9.0 shows that the effects of conversion from the deoxy to the liganded state in reducing the carbamino adduct formation occur predominantly at Val-1beta. Analysis of the pH dependence of carbamino formation at constant total carbonates yields values of pKz and pKc for Val-1beta and Val-1alpha in the deoxy and liganded conditions. In contrast to the Val-1beta as the allosteric site for CO2, the Val-1alpha site is shown to be primarily an alkaline Bohr group. 2,3-Diphosphoglycerate is shown to reduce substantially the Val-1beta carbamino resonance intensity in deoxyhemoglobin. Evidence for 2,3-diphosphoglycerate effects in carbon monoxide hemoglobin at both Val-1alpha and Val-1beta sites is presented. Enhanced carbamino formation in carbon monoxide hemoglobin at Val-1beta is observed at pH values less than 7.8. Finally, chemical exchange analysis of the spectra shows the release rate of the deoxy Val-1alpha carbamino adduct to be greater than that for deoxy Val-1beta. At pH 7.47 k-1obs,beta congruent to 1.0 and k-1obs, alpha congruent to 11.0 s-1."}
{"id": "PMID:14959", "title": "Distribution of sulfated mucopolysaccharides in invertebrates.", "content": "The sulfated mucopolysaccharide composition of 22 species of invertebrates belonging to the phyla Arthropoda, Mollusca, Annelida, Tunicata, Echinodermata, Coelenterata, and Porifera was analyzed. It is shown that all the species contain variable amounts of one or more types of sulfated mocopolysaccharides, most of which similar to the ones found in vertebrates. It is shown also that each species has a characteristic composition, differing from each other regarding the relative amount and type of chondroitin sulfates A, B, and C, heparitin sulfate, and heparin. The possible biological role of the sulfated mucopolysaccharides in cell recognition or aggregation or both is discussed in view of the present findings.", "contents": "Distribution of sulfated mucopolysaccharides in invertebrates. The sulfated mucopolysaccharide composition of 22 species of invertebrates belonging to the phyla Arthropoda, Mollusca, Annelida, Tunicata, Echinodermata, Coelenterata, and Porifera was analyzed. It is shown that all the species contain variable amounts of one or more types of sulfated mocopolysaccharides, most of which similar to the ones found in vertebrates. It is shown also that each species has a characteristic composition, differing from each other regarding the relative amount and type of chondroitin sulfates A, B, and C, heparitin sulfate, and heparin. The possible biological role of the sulfated mucopolysaccharides in cell recognition or aggregation or both is discussed in view of the present findings."}
{"id": "PMID:14960", "title": "Proton magnetic relaxation of aspartate transcarbamylase - succinate complexes.", "content": "Nuclear magnetic relaxation methods were used to investigate the interaction of the inhibitor succinate with aspartate transcarbamylase from Escherichia coli. Over the pH range 7 to 9, the dissociation constant for succinate remains less than the inhibitor concentration used for most of this work (0.05 M). As a result, the enzyme predominantly exists in a single \"gross\" conformational state. Succinate binding to this enzyme state (generally known as the R form) parallels the behavior seen previously with the isolated catalytic subunit (Beard, C. B., and Schmidt, P.G. (1973) Biochemistry 12, 2255-2264). The pH and temperature dependence of succinate proton relaxation rates, 1/T2 - 1/T1, in the presence of carbamyl phosphate, is interpreted in terms of a binding mechanism involving three forms of the enzyme, differing by their states of protonation. The least protonated form of the enzyme does not interact with succinate, the singly protonated species binds succinate to form a rapidly dissociating complex, and the doubly protonated species undergoes a conformational isomerization upon succinate binding, yielding a slow exchange complex. Relaxation data provide sufficient information to determine pKa values of 7.2 and 8.9 for two ionizing groups, as well as the dissociation constant for succinate in the fast exchange complex, Kd =1.6 X 10(-2) M. Rate constants for the forward and reverse steps of the isomerization, 1.3 X 10(3) s-1 and 33 s-1, respectively, indicate a significantly slower reverse rate from that obtained in the earlier NMR study of the isolated catalytic subunit. In experiments where the succinate concentration was varied, the relaxation rates showed sigmoidal binding of that ligand to the fast exchange complex above pH 9.1, (a) indicating cooperative binding of succinate, and (b) suggesting that above pH 9.1, the system cannot be characterized by a single dissociation constant, ionization constant, or relaxation effect. CTP and ATP were tested for their ability to affect succinate binding to the fast exchange complex. Heterotropic interactions were observed for CTP but not for ATP. Addition of low concentrations of the transition state analog N-(phosphonacetyl)-L-aspartate to the enzyme-carbamyl phosphate-succinate complex sharply decreased the relaxation rate, indicating that the measurements are sensitive only to succinate bound specifically to the active site.", "contents": "Proton magnetic relaxation of aspartate transcarbamylase - succinate complexes. Nuclear magnetic relaxation methods were used to investigate the interaction of the inhibitor succinate with aspartate transcarbamylase from Escherichia coli. Over the pH range 7 to 9, the dissociation constant for succinate remains less than the inhibitor concentration used for most of this work (0.05 M). As a result, the enzyme predominantly exists in a single \"gross\" conformational state. Succinate binding to this enzyme state (generally known as the R form) parallels the behavior seen previously with the isolated catalytic subunit (Beard, C. B., and Schmidt, P.G. (1973) Biochemistry 12, 2255-2264). The pH and temperature dependence of succinate proton relaxation rates, 1/T2 - 1/T1, in the presence of carbamyl phosphate, is interpreted in terms of a binding mechanism involving three forms of the enzyme, differing by their states of protonation. The least protonated form of the enzyme does not interact with succinate, the singly protonated species binds succinate to form a rapidly dissociating complex, and the doubly protonated species undergoes a conformational isomerization upon succinate binding, yielding a slow exchange complex. Relaxation data provide sufficient information to determine pKa values of 7.2 and 8.9 for two ionizing groups, as well as the dissociation constant for succinate in the fast exchange complex, Kd =1.6 X 10(-2) M. Rate constants for the forward and reverse steps of the isomerization, 1.3 X 10(3) s-1 and 33 s-1, respectively, indicate a significantly slower reverse rate from that obtained in the earlier NMR study of the isolated catalytic subunit. In experiments where the succinate concentration was varied, the relaxation rates showed sigmoidal binding of that ligand to the fast exchange complex above pH 9.1, (a) indicating cooperative binding of succinate, and (b) suggesting that above pH 9.1, the system cannot be characterized by a single dissociation constant, ionization constant, or relaxation effect. CTP and ATP were tested for their ability to affect succinate binding to the fast exchange complex. Heterotropic interactions were observed for CTP but not for ATP. Addition of low concentrations of the transition state analog N-(phosphonacetyl)-L-aspartate to the enzyme-carbamyl phosphate-succinate complex sharply decreased the relaxation rate, indicating that the measurements are sensitive only to succinate bound specifically to the active site."}
{"id": "PMID:14961", "title": "Two distinct types of trimethoprim-resistant dihydrofolate reductase specified by R-plasmids of different compatibility groups.", "content": "R-Plasmids from a number of trimethoprim-resistant Escherichia coli and Citrobacter sp. were studied after transfer to E. coli K12 hosts. Each was found to specify a dihydrofolate reductase which was resistant to trimethoprim and Methotrexate, and which could be completely separated from the host chromosomal enzyme by gel filtration. Two distinct types of R-plasmid dihydrofolate reductases were identified. Type I enzymes, typified by the R483 enzyme previously described (Sk\u00f6ld, O., and Widh, A. (1974) J. Biol. Chem. 249, 4324-4325), are synthesized in amounts severalfold higher than the chromosomal enzyme. The 50% inhibitory concentrations (I50) of trimethoprim, Methotrexate, and aminopterin are increased several thousandfold over the corresponding values for the chromosomal enzyme. Type II R-plasmid dihydrofolate reductases are synthesized in about the same amount, or less, as the chromosomal enzyme, but are practically several hundredfold higher than those for the type I enzymes. Both types of R-plasmid dihydrofolate reductase showed little difference from the chromosomal enzyme in the binding of dihydrofolate, NADPH, folic acid, and 2,4-diaminopyrimidine.", "contents": "Two distinct types of trimethoprim-resistant dihydrofolate reductase specified by R-plasmids of different compatibility groups. R-Plasmids from a number of trimethoprim-resistant Escherichia coli and Citrobacter sp. were studied after transfer to E. coli K12 hosts. Each was found to specify a dihydrofolate reductase which was resistant to trimethoprim and Methotrexate, and which could be completely separated from the host chromosomal enzyme by gel filtration. Two distinct types of R-plasmid dihydrofolate reductases were identified. Type I enzymes, typified by the R483 enzyme previously described (Sk\u00f6ld, O., and Widh, A. (1974) J. Biol. Chem. 249, 4324-4325), are synthesized in amounts severalfold higher than the chromosomal enzyme. The 50% inhibitory concentrations (I50) of trimethoprim, Methotrexate, and aminopterin are increased several thousandfold over the corresponding values for the chromosomal enzyme. Type II R-plasmid dihydrofolate reductases are synthesized in about the same amount, or less, as the chromosomal enzyme, but are practically several hundredfold higher than those for the type I enzymes. Both types of R-plasmid dihydrofolate reductase showed little difference from the chromosomal enzyme in the binding of dihydrofolate, NADPH, folic acid, and 2,4-diaminopyrimidine."}
{"id": "PMID:14962", "title": "Porcine A blood group-specific N-acetylgalactosaminyltransferase. I. Purification from porcine submaxillary glands.", "content": "The membrane-bound N-acetylgalactosaminyltransferase from porcine submaxillary glands which provides A blood group specificity to mucin has been purified 38,000-fold by affinity chromatography on UDP-hesanolamine-agarose in aqueous Triton X-100. Design of a suitable purification procedure was developed by assessing the strength of interaction between enzyme and affinity adsorbent using batch desorption. The pure transferase has an apparent molecular weight of 100,000 as judged by zonal centrifugation and by sodium dodecyl sulfate polyacrylamide gel electrophoresis in the absence of a reducing agent. The reduced and carboxymethylated protein has an apparent molecular weight of 46,000 and 57,000 as judged by sedimentation equilibrium and sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, suggesting that the native enzyme contains two subunits. It is a glycoprotein with a specific activity of 30 micronmol/min/mg of enzyme, which is 55,000 times that reported for the same enzyme isolated from human serum.", "contents": "Porcine A blood group-specific N-acetylgalactosaminyltransferase. I. Purification from porcine submaxillary glands. The membrane-bound N-acetylgalactosaminyltransferase from porcine submaxillary glands which provides A blood group specificity to mucin has been purified 38,000-fold by affinity chromatography on UDP-hesanolamine-agarose in aqueous Triton X-100. Design of a suitable purification procedure was developed by assessing the strength of interaction between enzyme and affinity adsorbent using batch desorption. The pure transferase has an apparent molecular weight of 100,000 as judged by zonal centrifugation and by sodium dodecyl sulfate polyacrylamide gel electrophoresis in the absence of a reducing agent. The reduced and carboxymethylated protein has an apparent molecular weight of 46,000 and 57,000 as judged by sedimentation equilibrium and sodium dodecyl sulfate polyacrylamide gel electrophoresis, respectively, suggesting that the native enzyme contains two subunits. It is a glycoprotein with a specific activity of 30 micronmol/min/mg of enzyme, which is 55,000 times that reported for the same enzyme isolated from human serum."}
{"id": "PMID:14963", "title": "Porcine A blood group-specific N-acetylgalactosaminyltransferase.", "content": "Porcine A blood group-specific N-acetylgalactosaminyl-transferase required either Mn2+, Cd2+, or Zn2+ for activity and 2'-O-alpha-fucosylgalactosides as acceptor substrates. The presence of detergent stabilizes the enzyme but is not essential for catalysis. To obtain information about the kinetic mechanism of the transferase reaction, initial rate parameters have been determined using 2'-fucosyllactose or A--mucin as acceptors, and Mn2+ or Cd2+ as cosubstrates. 2'-Fucosyllactose is a competitive inhibitor with respect to A--mucin and a noncompetitive inhibitor with respect to UDP-N-acetylgalactosamine. UDP inhibits noncompetively with respect to acceptor; thus UDP-N-acetylgalactosamine or acceptor can bind to the transferase via an equilibrium random pathway. The transferase converts human O blood type erythrocytes of A blood types. After exhaustive glycosylation, 3 X 10(6) N-acetylgalactosaminyl residues were incorporated per cell. Gel electrophoretic analysis of the labeled erythrocyte membranes indicates that glycoproteins with apparents molecular weights from 30,000 to 100,000 have been glycosylated; glycolipids account for only 15% of the labeled material, although pure H-glycolipid is a good acceptor. The transferase, with its strict acceptor specificity, can thus be used as a tool to study the biosynthesis and function of glycolipids and glycoproteins.", "contents": "Porcine A blood group-specific N-acetylgalactosaminyltransferase. Porcine A blood group-specific N-acetylgalactosaminyl-transferase required either Mn2+, Cd2+, or Zn2+ for activity and 2'-O-alpha-fucosylgalactosides as acceptor substrates. The presence of detergent stabilizes the enzyme but is not essential for catalysis. To obtain information about the kinetic mechanism of the transferase reaction, initial rate parameters have been determined using 2'-fucosyllactose or A--mucin as acceptors, and Mn2+ or Cd2+ as cosubstrates. 2'-Fucosyllactose is a competitive inhibitor with respect to A--mucin and a noncompetitive inhibitor with respect to UDP-N-acetylgalactosamine. UDP inhibits noncompetively with respect to acceptor; thus UDP-N-acetylgalactosamine or acceptor can bind to the transferase via an equilibrium random pathway. The transferase converts human O blood type erythrocytes of A blood types. After exhaustive glycosylation, 3 X 10(6) N-acetylgalactosaminyl residues were incorporated per cell. Gel electrophoretic analysis of the labeled erythrocyte membranes indicates that glycoproteins with apparents molecular weights from 30,000 to 100,000 have been glycosylated; glycolipids account for only 15% of the labeled material, although pure H-glycolipid is a good acceptor. The transferase, with its strict acceptor specificity, can thus be used as a tool to study the biosynthesis and function of glycolipids and glycoproteins."}
{"id": "PMID:14964", "title": "Chemical modification of the histidine residue in phospholipase A2 (Naja naja naja). A case of half-site reactivity.", "content": "Reaction of phospholipase A2 (Naja naja naja) with p-bromophenacyl bromidine leads to almost complete loss of enzymatic activity. The rate of inactivation is pH-dependent with pKa equals 6.9 for the ionizing residue. p-Bromophenacyl bromide modifies 0.5 mol of histidine/mol of enzyme as judged by amino acid analysis and incorporation studies with 14C-labeled reagent. The rate of inactivation is affected by various cations; a saturating concentration of Ca2+ decreases the rate 5-fold, while Mn2+ increases the rate by a factor of 2. Triton X-100, which by itself has little affinity for the enzyme, protects against inactivation, presumably by sequestering p-bromophenacyl bromide into the apolar micellar core. The mixed micelle system of Triton X-100, dipalmitoyl phosphatidylcholine, and Ba2+ offers the best protection, lowering the inactivation rate by at least 50-fold. This suggests an active site role for the histidine residue. Ethoxyformic anhydride also modifies phospholipase A2, by acylation of the two amino groups, a tyrosine, and 0.5 mol of histidine/mol of enzyme without totally inactivating the enzyme. Removal of the ethoxyformyl group from the histidine does not reactivate the enzyme. Thus, modification of 0.5 mol of histidine with this reagent is not responsible for the 85% loss of activity seen. Ethoxyformylated enzyme, with 0.5 mol of acylated histidine/mol of enzyme, can be further inactivated by treatment with p-bromophenacyl bromide. The resulting derivative contains 0.4 mol of the 14C-labeled p-bromophenacyl group. Other modifiable groups do not show this half-residue reactivity. For example, oxidation of phospholipase A2 with N-bromosuccinimide leads to rapid destruction of 1.0 tryptophan residue and 5% residual activity. The results of these chemical modification experiments can be interpreted in terms of a model in which the active species of enzyme interacting with mixed micelles is a dimer (or possibly higher order aggregate). The dimer, though composed of identical subunits, is asymmetric; the histidine of one subunit is accessible to ethoxyformic anhydride, while the other histidine is near a hydrophobic region of the enzyme and is chemically reactive toward p-bromophenacyl bromide.", "contents": "Chemical modification of the histidine residue in phospholipase A2 (Naja naja naja). A case of half-site reactivity. Reaction of phospholipase A2 (Naja naja naja) with p-bromophenacyl bromidine leads to almost complete loss of enzymatic activity. The rate of inactivation is pH-dependent with pKa equals 6.9 for the ionizing residue. p-Bromophenacyl bromide modifies 0.5 mol of histidine/mol of enzyme as judged by amino acid analysis and incorporation studies with 14C-labeled reagent. The rate of inactivation is affected by various cations; a saturating concentration of Ca2+ decreases the rate 5-fold, while Mn2+ increases the rate by a factor of 2. Triton X-100, which by itself has little affinity for the enzyme, protects against inactivation, presumably by sequestering p-bromophenacyl bromide into the apolar micellar core. The mixed micelle system of Triton X-100, dipalmitoyl phosphatidylcholine, and Ba2+ offers the best protection, lowering the inactivation rate by at least 50-fold. This suggests an active site role for the histidine residue. Ethoxyformic anhydride also modifies phospholipase A2, by acylation of the two amino groups, a tyrosine, and 0.5 mol of histidine/mol of enzyme without totally inactivating the enzyme. Removal of the ethoxyformyl group from the histidine does not reactivate the enzyme. Thus, modification of 0.5 mol of histidine with this reagent is not responsible for the 85% loss of activity seen. Ethoxyformylated enzyme, with 0.5 mol of acylated histidine/mol of enzyme, can be further inactivated by treatment with p-bromophenacyl bromide. The resulting derivative contains 0.4 mol of the 14C-labeled p-bromophenacyl group. Other modifiable groups do not show this half-residue reactivity. For example, oxidation of phospholipase A2 with N-bromosuccinimide leads to rapid destruction of 1.0 tryptophan residue and 5% residual activity. The results of these chemical modification experiments can be interpreted in terms of a model in which the active species of enzyme interacting with mixed micelles is a dimer (or possibly higher order aggregate). The dimer, though composed of identical subunits, is asymmetric; the histidine of one subunit is accessible to ethoxyformic anhydride, while the other histidine is near a hydrophobic region of the enzyme and is chemically reactive toward p-bromophenacyl bromide."}
{"id": "PMID:14965", "title": "Functional characterization of anion transport system isolated from human erythrocyte membranes.", "content": "The anion transport system of human red blood cells was isolated in vesicles containing the original lipids of the membrane and predominantly the 95,000-dalton polypeptides (Band 3) associated with intralipid particles. The vesicles display various characteristic properties of anion permeation closely resembling those of the native system. The properties include energy of activation, pH dependence, anion sleectivity, sensitivity to specific inhibitors, and exchange and net rates of sulfate transport. Based on these and other criteria, the functional properties of isolated vesicles could be equated with those of the intact cell system. Direct support for the involvement of 95,000-dalton polypeptides in permeation functions is provided.", "contents": "Functional characterization of anion transport system isolated from human erythrocyte membranes. The anion transport system of human red blood cells was isolated in vesicles containing the original lipids of the membrane and predominantly the 95,000-dalton polypeptides (Band 3) associated with intralipid particles. The vesicles display various characteristic properties of anion permeation closely resembling those of the native system. The properties include energy of activation, pH dependence, anion sleectivity, sensitivity to specific inhibitors, and exchange and net rates of sulfate transport. Based on these and other criteria, the functional properties of isolated vesicles could be equated with those of the intact cell system. Direct support for the involvement of 95,000-dalton polypeptides in permeation functions is provided."}
{"id": "PMID:14966", "title": "Phosphoglycolate phosphatase in human erythrocytes.", "content": "Human erythrocytes were found to contain an enzyme capable of dephosphorylating phosphoglycolate. The rates of hydrolysis of 14 other metabolites by the enzyme preparation were less than 6% of the rate with phosphoglycolate. The pH optimum is in the range of 6 to 7 and the Km for phosphoglycolate is 0.76 mM. The molecular weight appears to be about 79,000. Such an activity has previously been reported only for plant cells.", "contents": "Phosphoglycolate phosphatase in human erythrocytes. Human erythrocytes were found to contain an enzyme capable of dephosphorylating phosphoglycolate. The rates of hydrolysis of 14 other metabolites by the enzyme preparation were less than 6% of the rate with phosphoglycolate. The pH optimum is in the range of 6 to 7 and the Km for phosphoglycolate is 0.76 mM. The molecular weight appears to be about 79,000. Such an activity has previously been reported only for plant cells."}
{"id": "PMID:14967", "title": "The reactivity of alpha-chymotrypsin immobilized on radiation-grafted hydrogel surfaces.", "content": "The enzymatic activity of alpha-chymotrypsin (CT), immobilized on hydrogel-coated polymer film supports, has been investigated. The support was prepared by radiation-graft copolymerization of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAAc) on silicone rubber films. The enzyme was covalently coupled to the carboxylic group of MAAc via the N-hydroxysuccinimide (NHS) ester active intermediate. Increasing MAAc contents of the hydrogel resulted in increased attachment of CT. The integrity of the CT active site after attachment was assessed by an active site titration with diisopropyl fluorophosphate (DFP). As the MAAc content of the hydrogel was increased, an increasing fraction of the attached CT retained its activity to DFP. A greater fraction of CT was active towards DFP when adsorbed than when coupled. The rates of hydrolysis of some synthetic model substrates by the immobilized CT were also measured. The negative charge on the hydrogel had a large effect on the rates of these hydrolyses. The pH optimum for the hydrolysis of N-acetyl-L-tyrosine ethyl ester (ATEE) by immobilized CT was higher than that of free CT. Increasing MAAc content of the hydrogel resulted in larger shifts in the pH optimum. The maximum rates of ATEE hydroylsis per mg CT declined sharply with increasing MAAc content of the hydrogel. This is probably related to the increasing repulsive force between the ATEE (negatively charged above congruent to pH 9.5) and the hydrogel with increasing MAAc content. The activity of immobilized CT to ATEE is small compared to that of free CT, partly due to this charge effect. Conversely, the rate of hydrolysis of BAEE, a positively charged substrate, by immobilized CT at pH 11, is almost fourfold greater than that by free CT at its pH optimum.", "contents": "The reactivity of alpha-chymotrypsin immobilized on radiation-grafted hydrogel surfaces. The enzymatic activity of alpha-chymotrypsin (CT), immobilized on hydrogel-coated polymer film supports, has been investigated. The support was prepared by radiation-graft copolymerization of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAAc) on silicone rubber films. The enzyme was covalently coupled to the carboxylic group of MAAc via the N-hydroxysuccinimide (NHS) ester active intermediate. Increasing MAAc contents of the hydrogel resulted in increased attachment of CT. The integrity of the CT active site after attachment was assessed by an active site titration with diisopropyl fluorophosphate (DFP). As the MAAc content of the hydrogel was increased, an increasing fraction of the attached CT retained its activity to DFP. A greater fraction of CT was active towards DFP when adsorbed than when coupled. The rates of hydrolysis of some synthetic model substrates by the immobilized CT were also measured. The negative charge on the hydrogel had a large effect on the rates of these hydrolyses. The pH optimum for the hydrolysis of N-acetyl-L-tyrosine ethyl ester (ATEE) by immobilized CT was higher than that of free CT. Increasing MAAc content of the hydrogel resulted in larger shifts in the pH optimum. The maximum rates of ATEE hydroylsis per mg CT declined sharply with increasing MAAc content of the hydrogel. This is probably related to the increasing repulsive force between the ATEE (negatively charged above congruent to pH 9.5) and the hydrogel with increasing MAAc content. The activity of immobilized CT to ATEE is small compared to that of free CT, partly due to this charge effect. Conversely, the rate of hydrolysis of BAEE, a positively charged substrate, by immobilized CT at pH 11, is almost fourfold greater than that by free CT at its pH optimum."}
{"id": "PMID:14968", "title": "Mechanochemical studies of enzymatic degradation of insoluble collagen fibers.", "content": "A mechanochemical method was developed for studying the enzymatic degradation of insoluble collagen fibers. The method involves stretching the collagen fiber to a fixed extension in the presence of a solution of collagenase and measuring the rate of relaxation of the force induced in the fiber. In this work, bacterial collagenase was used for reasons of availability. We observed invariably an exponential decrease in force with respect to ttime. The slope of the linear plot of logarithm of the force versus time was taken as a measure of the rate of enzymatic degradation. This rate was found a) to vary linearly with collagenase concentration; b) to be maximal at pH 7-8; c) to vary with temperature according to the Arrhenius relationship in the range 10-56 degrees C; d) to be reduced to varying extent by addition of EDTA omicron-phenanthroline, 2,3-dimercaptopropanolol, and D,L-cysteine; e) to be minimal when the strain on the fiber was ca. 4%; f) to be increased dramatically by denaturation of the collagen fiber; and g) to be reduced by an increase in the crosslink density of the collagen fiber. Except for the effect of strain, which can not be conveniently studied by existing methods these results are consistent with those observed by other methods for the study of the enzymatic degradation of collagen. The mechanochemical method is, however, uniquely suited to monitor continuously the enzymatically induced decay in the stress-bearing ability of collagen fibers. It has also been found useful in the design of collagenous implants with specified resistance to enzymatic degradation in vivo.", "contents": "Mechanochemical studies of enzymatic degradation of insoluble collagen fibers. A mechanochemical method was developed for studying the enzymatic degradation of insoluble collagen fibers. The method involves stretching the collagen fiber to a fixed extension in the presence of a solution of collagenase and measuring the rate of relaxation of the force induced in the fiber. In this work, bacterial collagenase was used for reasons of availability. We observed invariably an exponential decrease in force with respect to ttime. The slope of the linear plot of logarithm of the force versus time was taken as a measure of the rate of enzymatic degradation. This rate was found a) to vary linearly with collagenase concentration; b) to be maximal at pH 7-8; c) to vary with temperature according to the Arrhenius relationship in the range 10-56 degrees C; d) to be reduced to varying extent by addition of EDTA omicron-phenanthroline, 2,3-dimercaptopropanolol, and D,L-cysteine; e) to be minimal when the strain on the fiber was ca. 4%; f) to be increased dramatically by denaturation of the collagen fiber; and g) to be reduced by an increase in the crosslink density of the collagen fiber. Except for the effect of strain, which can not be conveniently studied by existing methods these results are consistent with those observed by other methods for the study of the enzymatic degradation of collagen. The mechanochemical method is, however, uniquely suited to monitor continuously the enzymatically induced decay in the stress-bearing ability of collagen fibers. It has also been found useful in the design of collagenous implants with specified resistance to enzymatic degradation in vivo."}
{"id": "PMID:14969", "title": "Basal and stimulated serum growth hormone concentrations in inflammatory bowel disease.", "content": "Patients with inflammatory bowel disease (IBD) manifest growth failure which may antecede abdominal symptoms by some years. Eight of ten children with documented IBD had records of decreasing growth velocities. Investigation of growth hormone reserves showed excessive rather than impaired responses. Mean basal GH level was 6.2 +/- 0.75 (SEM) ng/ml. During sleep, the mean GH level rose to 26.0 +/- 4.7 ng/ml and following propranolol-glucagon stimulation, to 46.0 +/- 4.5 ng/ml. All values were significantly higher than levels obtained in a control population of 25 children investigated for short stature who were not GH deficient. The mean peak GH response following insulin in the IBD group (10.8 +/- 3.8 ng/ml), however, did not differ from the mean peak response in the control group (13.5 +/- 3.3 ng/ml). Growth failure in patients with IBD is not the result of GH deficiency and is not an irreversible phenomenon. On the contrary, judicious use of glucocorticoids aimed at the control of the disease usually produces compensatory growth acceleration (\"catch-up growth\").", "contents": "Basal and stimulated serum growth hormone concentrations in inflammatory bowel disease. Patients with inflammatory bowel disease (IBD) manifest growth failure which may antecede abdominal symptoms by some years. Eight of ten children with documented IBD had records of decreasing growth velocities. Investigation of growth hormone reserves showed excessive rather than impaired responses. Mean basal GH level was 6.2 +/- 0.75 (SEM) ng/ml. During sleep, the mean GH level rose to 26.0 +/- 4.7 ng/ml and following propranolol-glucagon stimulation, to 46.0 +/- 4.5 ng/ml. All values were significantly higher than levels obtained in a control population of 25 children investigated for short stature who were not GH deficient. The mean peak GH response following insulin in the IBD group (10.8 +/- 3.8 ng/ml), however, did not differ from the mean peak response in the control group (13.5 +/- 3.3 ng/ml). Growth failure in patients with IBD is not the result of GH deficiency and is not an irreversible phenomenon. On the contrary, judicious use of glucocorticoids aimed at the control of the disease usually produces compensatory growth acceleration (\"catch-up growth\")."}
{"id": "PMID:14970", "title": "Insulin, proinsulin, glucagon and gastrin in pancreatic tumors and in plasma of patients with organic hyperinsulinism.", "content": "Insulin, proinsulin, glucagon and gastrin were determined in extracts of tumors of 27 patients with pancreatic islet cell neoplasia of pancreas, in one patient with nesidioblastosis, in extracts of uninvolved portions of the pancreas in 11 of the tumor patients and of 15 control pancreases. Mean insulin concentration in solitary adenomas and in adenomas of patients with adenomatosis was higher than in control pancreases; however, in all but 1 patient the insulin concentration in neoplastic islet tissue was lower than in islet tissue of control pancreas, assuming islet volume is 1% of pancreas. The percentage of proinsulin was elevated in 52% of tumors. Adenoma insulin content correlated with increments of plasma insulin after tolbutamide administration. Insulin and proinsulin concentrations in pancreas uninvolved by tumor were not suppressed. Fasting plasma glucagon was elevated in patients with islet cell adenomatosis and in patients with islet cell carcinoma some of whom had multiple endocrine adenomatosis. The mean concentration of glucagon in tumors was lower than in control pancreases. Elevated concentration of gastrin was found in some adenomas. The data indicate: 1) insulin-secreting islet cell tumors have decreased storage capacity for insulin, 2) elevated concentration of proinsulin in tumors may be due to decreased capacity to store insulin and in some to decreased conversion of proinsulin to insulin as well, 3) tolbutamide stimulates the exaggerated release of a relatively constant fraction of insulin stored in adenomas. 4) solitary adenomas may contain excess amounts of pancreatic hormones in addition to insulin, 5) elevated plasma glucagon in patients with organic hyperinsulinism may indicate malignancy, microadenomatosis or multiple endocrine adenoma syndrome, and 6) chronic hyperinsulinism and hypoglycemia due to adenoma do not suppress insulin and proinsulin content of uninvolved pancreas.", "contents": "Insulin, proinsulin, glucagon and gastrin in pancreatic tumors and in plasma of patients with organic hyperinsulinism. Insulin, proinsulin, glucagon and gastrin were determined in extracts of tumors of 27 patients with pancreatic islet cell neoplasia of pancreas, in one patient with nesidioblastosis, in extracts of uninvolved portions of the pancreas in 11 of the tumor patients and of 15 control pancreases. Mean insulin concentration in solitary adenomas and in adenomas of patients with adenomatosis was higher than in control pancreases; however, in all but 1 patient the insulin concentration in neoplastic islet tissue was lower than in islet tissue of control pancreas, assuming islet volume is 1% of pancreas. The percentage of proinsulin was elevated in 52% of tumors. Adenoma insulin content correlated with increments of plasma insulin after tolbutamide administration. Insulin and proinsulin concentrations in pancreas uninvolved by tumor were not suppressed. Fasting plasma glucagon was elevated in patients with islet cell adenomatosis and in patients with islet cell carcinoma some of whom had multiple endocrine adenomatosis. The mean concentration of glucagon in tumors was lower than in control pancreases. Elevated concentration of gastrin was found in some adenomas. The data indicate: 1) insulin-secreting islet cell tumors have decreased storage capacity for insulin, 2) elevated concentration of proinsulin in tumors may be due to decreased capacity to store insulin and in some to decreased conversion of proinsulin to insulin as well, 3) tolbutamide stimulates the exaggerated release of a relatively constant fraction of insulin stored in adenomas. 4) solitary adenomas may contain excess amounts of pancreatic hormones in addition to insulin, 5) elevated plasma glucagon in patients with organic hyperinsulinism may indicate malignancy, microadenomatosis or multiple endocrine adenoma syndrome, and 6) chronic hyperinsulinism and hypoglycemia due to adenoma do not suppress insulin and proinsulin content of uninvolved pancreas."}
{"id": "PMID:14971", "title": "Changes in occurrence of capsular serotypes of Streptococcus pneumoniae at Boston City Hospital during selected years between 1935 and 1974.", "content": "The number of patients with pneumococcal bacteremia, empyema, and meningitis at Boston City Hospital during selected years between 1935 and 1974 is reported. The distribution of specific types in the bacteremic patients during each of the selected years and in the various focal infections in all the years is also detailed. The numbers and rates per 1,000 admissions of bacteremic pneumococcal infections and the numbers of cases of pneumococcal meningitis and empyema varied independently over these years and differed from those previously reported for 1929 to 1936. The types most frequent in pneumococcal bacteremias varied over the years, and the distribution of types among them differed markedly from that among the patients with focal infections. Variations in the distribution of pneumococcal types at different times in the same place, in different places, and in various sites of infection may be important in selecting types to include in pneumococcal vaccines for different populations.", "contents": "Changes in occurrence of capsular serotypes of Streptococcus pneumoniae at Boston City Hospital during selected years between 1935 and 1974. The number of patients with pneumococcal bacteremia, empyema, and meningitis at Boston City Hospital during selected years between 1935 and 1974 is reported. The distribution of specific types in the bacteremic patients during each of the selected years and in the various focal infections in all the years is also detailed. The numbers and rates per 1,000 admissions of bacteremic pneumococcal infections and the numbers of cases of pneumococcal meningitis and empyema varied independently over these years and differed from those previously reported for 1929 to 1936. The types most frequent in pneumococcal bacteremias varied over the years, and the distribution of types among them differed markedly from that among the patients with focal infections. Variations in the distribution of pneumococcal types at different times in the same place, in different places, and in various sites of infection may be important in selecting types to include in pneumococcal vaccines for different populations."}
{"id": "PMID:14972", "title": "Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival.", "content": "73 consecutive patients with severe aplastic anemia were treated by marrow transplantation from hematologically normal HLA identical siblings. 68 patients lived long enough to document marrow engraftment. 21 rejected the graft and 19 of these died. 47 sustained engraftment and 18 of these died. In 16 patients, death was associated with graft versus host disease. 29 patients with sustained engraftment are alive with complete hematologic restoration between 8 mo and 5 yr. This analysis, by using a proportional hazards regression model, was directed at identifying factors that predicted survival (and absence of graft versus host disease). Of the 24 factors entered into the analysis only two strongly correlated with survival: (a) sex match of donor and recipient (P less than 0.01), and (b) absence of refractoriness to random donor platelets at the time of transplantation (P less than 0.05). Refractoriness adversely influenced the survival of the sex mismatched patients, These data suggest that X and Y-associated transplantation antigen systems are important determinants of the outcome of marrow grafts between HLA identical siblings for the treatment of aplastic anemia. The machanism by which refractoriness to random donor platelets influences survival is currently unclear.", "contents": "Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival. 73 consecutive patients with severe aplastic anemia were treated by marrow transplantation from hematologically normal HLA identical siblings. 68 patients lived long enough to document marrow engraftment. 21 rejected the graft and 19 of these died. 47 sustained engraftment and 18 of these died. In 16 patients, death was associated with graft versus host disease. 29 patients with sustained engraftment are alive with complete hematologic restoration between 8 mo and 5 yr. This analysis, by using a proportional hazards regression model, was directed at identifying factors that predicted survival (and absence of graft versus host disease). Of the 24 factors entered into the analysis only two strongly correlated with survival: (a) sex match of donor and recipient (P less than 0.01), and (b) absence of refractoriness to random donor platelets at the time of transplantation (P less than 0.05). Refractoriness adversely influenced the survival of the sex mismatched patients, These data suggest that X and Y-associated transplantation antigen systems are important determinants of the outcome of marrow grafts between HLA identical siblings for the treatment of aplastic anemia. The machanism by which refractoriness to random donor platelets influences survival is currently unclear."}
{"id": "PMID:14973", "title": "Postsynthetic deamidation of hemoglobin Providence (beta 82 Lys replaced by Asn, Asp) and its effect on oxygen transport.", "content": "Carriers of hemoglobin Providence have three types of beta chain in their hemolysates. The two abnormal chains have asparagine (Providence N, Prov N) or aspartic acid (Providence D) at position beta 82, instead of lysine. In vitro, only two beta chains are synthesized by reticulocytes of carriers, betaA and betaProv N. In vivo studies showed that the specific activity of Providence N was initially 10-fold higher than that of Providence D; the specific activities of the two labeled hemoglobins were approximately equal 5 wk after injection of isotope. Oxygen affinity of carriers' blood was somewhat increased, but they were not polycythemic. The affinity of the purified hemoglobins Providence was decreased. Addition of 2, 3 diphosphoglycerate had little effect on the affinity of either hemoglobin component, and addition of inositol hexaphosphate produced no change in the affinity of Providence D. These studies demonstrate that Providence N is deamidated to Providence D during the life span of the erythrocyte, and suggest this finding may represent only an easily observed prototype of posttranslational modification of proteins in general. Despite and abnormal P50 of the blood, oxygen transport is probably normal in carriers of the abnormal hemoglobins.", "contents": "Postsynthetic deamidation of hemoglobin Providence (beta 82 Lys replaced by Asn, Asp) and its effect on oxygen transport. Carriers of hemoglobin Providence have three types of beta chain in their hemolysates. The two abnormal chains have asparagine (Providence N, Prov N) or aspartic acid (Providence D) at position beta 82, instead of lysine. In vitro, only two beta chains are synthesized by reticulocytes of carriers, betaA and betaProv N. In vivo studies showed that the specific activity of Providence N was initially 10-fold higher than that of Providence D; the specific activities of the two labeled hemoglobins were approximately equal 5 wk after injection of isotope. Oxygen affinity of carriers' blood was somewhat increased, but they were not polycythemic. The affinity of the purified hemoglobins Providence was decreased. Addition of 2, 3 diphosphoglycerate had little effect on the affinity of either hemoglobin component, and addition of inositol hexaphosphate produced no change in the affinity of Providence D. These studies demonstrate that Providence N is deamidated to Providence D during the life span of the erythrocyte, and suggest this finding may represent only an easily observed prototype of posttranslational modification of proteins in general. Despite and abnormal P50 of the blood, oxygen transport is probably normal in carriers of the abnormal hemoglobins."}
{"id": "PMID:14974", "title": "Mechanism of resistance to the phosphaturic effect of the parathyroid hormone in the hamster.", "content": "The effect of parathyroid hormone and calcitonin on the renal excretion of phosphate, calcium, and cyclic AMP was evaluated in the thyroparathyroidectomized hamster, a mammal apparently reisstant to the phosphaturic effect of parathyroid hormone. Parathyroid hormone did not increase phosphate excretion, although it decreased excretion of calcium and increased urinary excretion of cyclic AMP. This lack of a phosphaturic response to parathyroid hormone was not reversed by administration of 25-OH vitamin D or infusions of calcium or phosphate. Calcitonin, another potentially phosphaturic hormone, also vailed to increase phosphate excretion but markedly elevated urinary excretion of cyclic AMP. In hamsters pretreated with infusion of urinary ammonium chloride, which decreased plasma and urinary pH, both parathyroid hormone and calcitonin increased excretion of phosphate as well as that of cyclic AMP. Acetazolamide had no phosphaturic effect in ammonium chloride-loaded hamsters, and it decreased cyclic AMP and calcium excretion. Alkalinization of urine by acetazolamide did not prevent the phosphaturic effect of parathyroid hormone in ammonium chloride-loaded hamsters, but it blocked the increase in urinary cyclic AMP excretion. Parathyroid hormone and calcitonin both stimulated adenylate cyclase in a cell-free system (600-g pellet) from hamster renal cortex, elevated tissue cyclic AMP levels, and activated protein kinase in tissue slices from hamster renal cortex. In acid medium, the increase in cyclic AMP and activation of protein kinase in response to parathyroid hormone was diminished, but addition of acetazolamide restored responsiveness of both parameters to control values. Acetazolamide, on the other hand, did not influence adenylate cyclase or its response to parathyroid hormone or cyclic AMP phosphodiesterase activity. We conclude that the lack of a phosphaturic effect of parathyroid hormone and calcitonin in the hamster depends on steps in the cellular action of these hormones, steps that are sensitive to pH subsequent to cyclic AMP generation and protein kinase activation. In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue. Thus, the hamster is a particularly useful model for studies of syndromes in which there is renal resistance to phosphaturic hormones.", "contents": "Mechanism of resistance to the phosphaturic effect of the parathyroid hormone in the hamster. The effect of parathyroid hormone and calcitonin on the renal excretion of phosphate, calcium, and cyclic AMP was evaluated in the thyroparathyroidectomized hamster, a mammal apparently reisstant to the phosphaturic effect of parathyroid hormone. Parathyroid hormone did not increase phosphate excretion, although it decreased excretion of calcium and increased urinary excretion of cyclic AMP. This lack of a phosphaturic response to parathyroid hormone was not reversed by administration of 25-OH vitamin D or infusions of calcium or phosphate. Calcitonin, another potentially phosphaturic hormone, also vailed to increase phosphate excretion but markedly elevated urinary excretion of cyclic AMP. In hamsters pretreated with infusion of urinary ammonium chloride, which decreased plasma and urinary pH, both parathyroid hormone and calcitonin increased excretion of phosphate as well as that of cyclic AMP. Acetazolamide had no phosphaturic effect in ammonium chloride-loaded hamsters, and it decreased cyclic AMP and calcium excretion. Alkalinization of urine by acetazolamide did not prevent the phosphaturic effect of parathyroid hormone in ammonium chloride-loaded hamsters, but it blocked the increase in urinary cyclic AMP excretion. Parathyroid hormone and calcitonin both stimulated adenylate cyclase in a cell-free system (600-g pellet) from hamster renal cortex, elevated tissue cyclic AMP levels, and activated protein kinase in tissue slices from hamster renal cortex. In acid medium, the increase in cyclic AMP and activation of protein kinase in response to parathyroid hormone was diminished, but addition of acetazolamide restored responsiveness of both parameters to control values. Acetazolamide, on the other hand, did not influence adenylate cyclase or its response to parathyroid hormone or cyclic AMP phosphodiesterase activity. We conclude that the lack of a phosphaturic effect of parathyroid hormone and calcitonin in the hamster depends on steps in the cellular action of these hormones, steps that are sensitive to pH subsequent to cyclic AMP generation and protein kinase activation. In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue. Thus, the hamster is a particularly useful model for studies of syndromes in which there is renal resistance to phosphaturic hormones."}
{"id": "PMID:14975", "title": "Serological grouping of streptococci by a slide coagglutination method.", "content": "A new method for the serological grouping of streptococci by coagglutination with specific antibodies absorbed to protein A-containing staphylococci has been assessed. A total of 242 strains of streptococci, including beta-haemolytic streptococci of groups A, B, C, F, and G, Streptococcus pneumoniae and Strep. faecalis were studied. All streptococci of groups A, B, C, and G, groupable by standard methods, were correctly grouped by coagglutination, although 7-3%  showed varying degrees of cross-agglutination. Two beta-haemolytic strains of Strep. faecalis produced coagglutination with group C streptococcal reagent. The method appears to be quick, accurate, reproducible, and simple to perform.", "contents": "Serological grouping of streptococci by a slide coagglutination method. A new method for the serological grouping of streptococci by coagglutination with specific antibodies absorbed to protein A-containing staphylococci has been assessed. A total of 242 strains of streptococci, including beta-haemolytic streptococci of groups A, B, C, F, and G, Streptococcus pneumoniae and Strep. faecalis were studied. All streptococci of groups A, B, C, and G, groupable by standard methods, were correctly grouped by coagglutination, although 7-3%  showed varying degrees of cross-agglutination. Two beta-haemolytic strains of Strep. faecalis produced coagglutination with group C streptococcal reagent. The method appears to be quick, accurate, reproducible, and simple to perform."}
{"id": "PMID:14976", "title": "Plasma level studies of penbutolol after oral dose in man.", "content": "Plasma levels of penbutolol (HOE 893d) were determined in eight healthy adult male subjects after oral administration of 50-mg capsules. Fast absorpiton of the drug from the gastrointestinal tract was indicated by the rapid increase in plasma levels during the absorption phase, with a peak time at about 1 hour after dosing in all subjects. After the peak level, plasma concentrations declined biexponentially, with an average half-life of 2.5 and 27 hours for the fast and slow disposition phases, respectively. These values were in good agreement with data previously found for this drug. Cumulative excretion of intact drug in the urine of the eight subjects during 72 hours after dosing was less than 4 per cent, except for one subject who excreted 9.82 per cent of the dose. Large individual variations were found for area under the plasma level curves, disposition rates, and amounts of intact drug excreted in the urine. Significant pharmacologic effects were noted in all eight subjects at the 50-mg dose level, and mild side effects were evident in one half of these subjects. The average drop in blood pressure and pulse rate for all subjects was 26/18 mm Hg and 19 beats per minute, respectively.", "contents": "Plasma level studies of penbutolol after oral dose in man. Plasma levels of penbutolol (HOE 893d) were determined in eight healthy adult male subjects after oral administration of 50-mg capsules. Fast absorpiton of the drug from the gastrointestinal tract was indicated by the rapid increase in plasma levels during the absorption phase, with a peak time at about 1 hour after dosing in all subjects. After the peak level, plasma concentrations declined biexponentially, with an average half-life of 2.5 and 27 hours for the fast and slow disposition phases, respectively. These values were in good agreement with data previously found for this drug. Cumulative excretion of intact drug in the urine of the eight subjects during 72 hours after dosing was less than 4 per cent, except for one subject who excreted 9.82 per cent of the dose. Large individual variations were found for area under the plasma level curves, disposition rates, and amounts of intact drug excreted in the urine. Significant pharmacologic effects were noted in all eight subjects at the 50-mg dose level, and mild side effects were evident in one half of these subjects. The average drop in blood pressure and pulse rate for all subjects was 26/18 mm Hg and 19 beats per minute, respectively."}
{"id": "PMID:14977", "title": "Penfluridol, a peroral long-acting neuroleptic, for the maintenance treatment of schizophrenic patients who relapse.", "content": "In a multicenter collaborative study, 28 newly readmitted schizophrenic patients, stabilized for one week on short-acting neuroleptic drugs, had their medication abruptly changed to penfluridol given once a week on an outpatient basis. The average dose required for maintenance was approximately 40 mg weekly. Analysis of BPRS evaluations carried out during the 16-week trial revealed a significant linear trend toward further improvement. Social functioning, as measured by the KAS questionnaire in the outpatient period of the trial, also revealed a significant linear trend toward improvement. Significant worsening was not found with any psychometric evaluation. Side effects, when observed, were neither frequent nor severe. Three laboratory and vital sign values showed significant changes: increase in BUN concentrations, decrease in pulse rate, and increase in body weight. The changes in weight and pulse appeared to be within relatively normal ranges, and the increase in BUN concentrations did not appear to be clinically significant. During the first part of a long-term study, penfluridol received a high degree of patient acceptability and is a welcome addition to the maintenance treatment of schizophrenia.", "contents": "Penfluridol, a peroral long-acting neuroleptic, for the maintenance treatment of schizophrenic patients who relapse. In a multicenter collaborative study, 28 newly readmitted schizophrenic patients, stabilized for one week on short-acting neuroleptic drugs, had their medication abruptly changed to penfluridol given once a week on an outpatient basis. The average dose required for maintenance was approximately 40 mg weekly. Analysis of BPRS evaluations carried out during the 16-week trial revealed a significant linear trend toward further improvement. Social functioning, as measured by the KAS questionnaire in the outpatient period of the trial, also revealed a significant linear trend toward improvement. Significant worsening was not found with any psychometric evaluation. Side effects, when observed, were neither frequent nor severe. Three laboratory and vital sign values showed significant changes: increase in BUN concentrations, decrease in pulse rate, and increase in body weight. The changes in weight and pulse appeared to be within relatively normal ranges, and the increase in BUN concentrations did not appear to be clinically significant. During the first part of a long-term study, penfluridol received a high degree of patient acceptability and is a welcome addition to the maintenance treatment of schizophrenia."}
{"id": "PMID:14978", "title": "Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine.", "content": "Sodium nitroprusside, nitroglycerin, sodium azide and hydroxylamine increased guanylate cyclase activity in particulate and/or soluble preparations from various tissues. While sodium nitroprusside increased guanylate cyclase activity in most of the preparations examined, the effects of sodium azide, hydroxylamine and nitroglycerin were tissue specific. Nitroglycerin and hydroxylamine were also less potent. Neither the protein activator factor nor catalase which is required for sodium azide effects altered the stimulatory effect of sodium nitroprusside. In the presence of sodium azide, sodium nitroprusside or hydroxylamine, magnesium ion was as effective as manganese ion as a sole cation cofactor for guanylate cyclase. With soluble guanylate cyclase from rat liver and bovine tracheal smooth muscle the concentrations of sodium nitroprusside that gave half-maximal stimulation with Mn2+ were 0.1 mM and 0.01 mM, respectively. Effective concentrations were slightly less with Mg2+ as a sole cation cofactor. The ability of these agents to increase cyclic GMP levels in intact tissues is probably due to their effects on guanylate cyclase activity. While the precise mechanism of guanylate cyclase activation by these agents is not known, activation may be due to the formation of nitric oxide or another reactive material since nitric oxide also increased guanylate cyclase activity.", "contents": "Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. Sodium nitroprusside, nitroglycerin, sodium azide and hydroxylamine increased guanylate cyclase activity in particulate and/or soluble preparations from various tissues. While sodium nitroprusside increased guanylate cyclase activity in most of the preparations examined, the effects of sodium azide, hydroxylamine and nitroglycerin were tissue specific. Nitroglycerin and hydroxylamine were also less potent. Neither the protein activator factor nor catalase which is required for sodium azide effects altered the stimulatory effect of sodium nitroprusside. In the presence of sodium azide, sodium nitroprusside or hydroxylamine, magnesium ion was as effective as manganese ion as a sole cation cofactor for guanylate cyclase. With soluble guanylate cyclase from rat liver and bovine tracheal smooth muscle the concentrations of sodium nitroprusside that gave half-maximal stimulation with Mn2+ were 0.1 mM and 0.01 mM, respectively. Effective concentrations were slightly less with Mg2+ as a sole cation cofactor. The ability of these agents to increase cyclic GMP levels in intact tissues is probably due to their effects on guanylate cyclase activity. While the precise mechanism of guanylate cyclase activation by these agents is not known, activation may be due to the formation of nitric oxide or another reactive material since nitric oxide also increased guanylate cyclase activity."}
{"id": "PMID:14979", "title": "The effect of adenylate cyclase inhibitor (ACI) on guanylate cyclase, phosphodiesterase and other enzymes in heart.", "content": "The effect of an inhibitor of adenylate cyclase (ACI) was measured on some enzymes associated with cyclic nucleotide-regulated metabolism. Soluble guanylate cyclase was inhibited; both soluble and particulate cyclic GMP-phosphodiesterases were stimulated. Cyclic AMP phosphodiesterases were unaffected. In contrast, the activities of Na, K-ATPase, protein kinase, phosphorylase kinase, glycogen synthetase and a number of glycosidases were not altered by equipotent amounts of the inhibitor. It is concluded that this substance acts as a modulator of both cyclic AMP and cyclic GMP metabolism in heart and other tissues.", "contents": "The effect of adenylate cyclase inhibitor (ACI) on guanylate cyclase, phosphodiesterase and other enzymes in heart. The effect of an inhibitor of adenylate cyclase (ACI) was measured on some enzymes associated with cyclic nucleotide-regulated metabolism. Soluble guanylate cyclase was inhibited; both soluble and particulate cyclic GMP-phosphodiesterases were stimulated. Cyclic AMP phosphodiesterases were unaffected. In contrast, the activities of Na, K-ATPase, protein kinase, phosphorylase kinase, glycogen synthetase and a number of glycosidases were not altered by equipotent amounts of the inhibitor. It is concluded that this substance acts as a modulator of both cyclic AMP and cyclic GMP metabolism in heart and other tissues."}
{"id": "PMID:14982", "title": "Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis.", "content": "A double-blind, vehicle control, parallel clinical trial evaluated the effectiveness and safety of the local application of flunisolide, a potent new topical steroid, in the treatment of ragweed hay fever. Fifty patients with well-defined, poorly controlled ragweed allergy were studied during the 1974 ragweed season. Analysis of the data showed that the active drug group had a significant decrease in individual symptoms of sneezing, nasal stuffiness, and nasal secretions, compared with the placebo group. Antihistamine usage was statistically decreased in the active drug over placebo group. There was no evidence of adrenal suppression. This study indicates that intranasal administration of flunisolide in adult patients is both efficacious and safe in the treatment of seasonal allergic rhinitis.", "contents": "Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis. A double-blind, vehicle control, parallel clinical trial evaluated the effectiveness and safety of the local application of flunisolide, a potent new topical steroid, in the treatment of ragweed hay fever. Fifty patients with well-defined, poorly controlled ragweed allergy were studied during the 1974 ragweed season. Analysis of the data showed that the active drug group had a significant decrease in individual symptoms of sneezing, nasal stuffiness, and nasal secretions, compared with the placebo group. Antihistamine usage was statistically decreased in the active drug over placebo group. There was no evidence of adrenal suppression. This study indicates that intranasal administration of flunisolide in adult patients is both efficacious and safe in the treatment of seasonal allergic rhinitis."}
{"id": "PMID:14987", "title": "Adverse effects of the drugs most frequently administered to the elderly--Part II.", "content": "The uncertainties associated with identificatin of adverse drug reactions are numerous. These effects which involve the eyes and vision constitute an important group but they are inadequately described and classified in most reports. Vague statements of visual disturbances, blur, changes in color vision, or difficulties in reading are indicated in many articles. Both parts of this report provide a listing of potential adverse effects, systemic and ocular. The drug groups included in part II are the antipsychotics, antianxiety drugs, antidepressants, antiparkinson drug and a miscellaneous group.", "contents": "Adverse effects of the drugs most frequently administered to the elderly--Part II. The uncertainties associated with identificatin of adverse drug reactions are numerous. These effects which involve the eyes and vision constitute an important group but they are inadequately described and classified in most reports. Vague statements of visual disturbances, blur, changes in color vision, or difficulties in reading are indicated in many articles. Both parts of this report provide a listing of potential adverse effects, systemic and ocular. The drug groups included in part II are the antipsychotics, antianxiety drugs, antidepressants, antiparkinson drug and a miscellaneous group."}
{"id": "PMID:15030", "title": "Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen.", "content": "The immune response to a thymus-dependent antigen was depressed in vivo and in vitro in spleen cells from mice injected with LPS i.p. a few days before challenge with the antigen. Spleen cells from LPS-injected mice could, however, respond with increase DNA synthesis after activation with polyclonal B and T cell activators in vitro. The LPS-activated spleen cells could actively suppress normal cells in their response to the antigen sheep red blood cells. The suppressor cells contained in the LPS-activated spleens were most likely B lymphocytes, and the possible mechanism for their inhibitory function is discussed.", "contents": "Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen. The immune response to a thymus-dependent antigen was depressed in vivo and in vitro in spleen cells from mice injected with LPS i.p. a few days before challenge with the antigen. Spleen cells from LPS-injected mice could, however, respond with increase DNA synthesis after activation with polyclonal B and T cell activators in vitro. The LPS-activated spleen cells could actively suppress normal cells in their response to the antigen sheep red blood cells. The suppressor cells contained in the LPS-activated spleens were most likely B lymphocytes, and the possible mechanism for their inhibitory function is discussed."}
{"id": "PMID:15031", "title": "Heterologous antigenic stimulation in induction of delayed hypersensitivity.", "content": "An influence of a delayed hypersensitive reaction to a primary antigen on the induction of delayed hypersensitivity to a second unrelated antigen was observed in guinea pigs immunized with azobenzenearsonate-N-acetyl-L-tyrosine (ABAT), and injected intradermally 3 weeks later with a mixture of ABAT and secondary antigen. Animals so treated developed delayed hypersensitivity to sheep red blood cells (SRBC) or Type II pneumococcal polysaccharide as secondary antigens, as measured by skin test reactivity and inhibition of macrophage migration, whereas ABAT unsensitized control groups did not. However, attempts to induce delayed reactivity to proteins as secondary antigens were unsuccessful. The injection of secondary antigen into a mineral oil-induced inflammatory lesion did not induce delayed hypersensitivity, suggesting that specific reactivity to ABAT is a prerequisite for heterologous induction. Possible mechanisms for the observed phenomenon, including a role for macrophages, are discussed.", "contents": "Heterologous antigenic stimulation in induction of delayed hypersensitivity. An influence of a delayed hypersensitive reaction to a primary antigen on the induction of delayed hypersensitivity to a second unrelated antigen was observed in guinea pigs immunized with azobenzenearsonate-N-acetyl-L-tyrosine (ABAT), and injected intradermally 3 weeks later with a mixture of ABAT and secondary antigen. Animals so treated developed delayed hypersensitivity to sheep red blood cells (SRBC) or Type II pneumococcal polysaccharide as secondary antigens, as measured by skin test reactivity and inhibition of macrophage migration, whereas ABAT unsensitized control groups did not. However, attempts to induce delayed reactivity to proteins as secondary antigens were unsuccessful. The injection of secondary antigen into a mineral oil-induced inflammatory lesion did not induce delayed hypersensitivity, suggesting that specific reactivity to ABAT is a prerequisite for heterologous induction. Possible mechanisms for the observed phenomenon, including a role for macrophages, are discussed."}
{"id": "PMID:15032", "title": "Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide I. Comparison of the suppression induced by con A and low dose paralysis.", "content": "Concanavalin A (Con A) administered at the time of immunization induces suppression of the in vivo splenic plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III). As with low dose paralysis of the PFC response to SSS-III, Con A-induced suppression could not be demonstrated in congenitally athymic (nu/nu) mice and could be eliminated partially by treatment with anti-lymphocyte serum (ALS). The kinetics for Con A-induced suppression paralleled those for low dose paralysis of the antibody response to SSS-III. These findings support the view that Con A-induced suppression is produced in vivo by suppressor T cells and that this form of suppression shares with low dose paralysis a common pathway through which suppression is mediated.", "contents": "Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide I. Comparison of the suppression induced by con A and low dose paralysis. Concanavalin A (Con A) administered at the time of immunization induces suppression of the in vivo splenic plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III). As with low dose paralysis of the PFC response to SSS-III, Con A-induced suppression could not be demonstrated in congenitally athymic (nu/nu) mice and could be eliminated partially by treatment with anti-lymphocyte serum (ALS). The kinetics for Con A-induced suppression paralleled those for low dose paralysis of the antibody response to SSS-III. These findings support the view that Con A-induced suppression is produced in vivo by suppressor T cells and that this form of suppression shares with low dose paralysis a common pathway through which suppression is mediated."}
{"id": "PMID:15033", "title": "Cell lines from old immunodeficient donors give normal responses in young recipients.", "content": "Two different immune responses were compared in spleen cells obtained from old and young CBA/HT6J mice. Spleen cells from old mice (23 to 33 months) responded about half as well as did spleen cells from young mice (4 to 10 months) in the adoptive transfer anti-sheep red blood cell (SRBC) plague-forming assay, and caused slightly less than half the uptake of tritiated thymidine in response to phytohemagglutinin (PHA) in vitro. Marrow stem cell from some of the old and young mice whose splenic immune responses were tested were transplanted into irradiated young CBA/CaJ recipients. Seven to 17 weeks later these same immune responses were tested in the spleen cells of these young recipients, and the T6 chromosome marker was used to identify donor cells. Old animals' responses varied greatly, perhaps due to suppressing cells or factors in some individuals. Therefore, cells were never pooled and the responses of receipients were compared to the responses of the donor whose marrow had populated them. The response for a particular old donor, or for the recipients of its stem cells, was divided by the response for the young control used with that donor, or for its stem cell recipients. This was called the old/young ratio. With original donors with an old/young ratio for the SRBC response of (mean  +/- S.D.) 0.35 +/- 0.14, The old/young ratio for that same response in the recipients was significantly improved to 1.26 +/- 0.71. In original donors with an old/young ratio for the PHA response of 0.44 +/- 0.17, the old/young ratio in the recipients improved significantly to 0.86 +/- 0.27. Thus, little or none of the decline with age in these immune responses was intrinsic to the old lymphoid stem cells.", "contents": "Cell lines from old immunodeficient donors give normal responses in young recipients. Two different immune responses were compared in spleen cells obtained from old and young CBA/HT6J mice. Spleen cells from old mice (23 to 33 months) responded about half as well as did spleen cells from young mice (4 to 10 months) in the adoptive transfer anti-sheep red blood cell (SRBC) plague-forming assay, and caused slightly less than half the uptake of tritiated thymidine in response to phytohemagglutinin (PHA) in vitro. Marrow stem cell from some of the old and young mice whose splenic immune responses were tested were transplanted into irradiated young CBA/CaJ recipients. Seven to 17 weeks later these same immune responses were tested in the spleen cells of these young recipients, and the T6 chromosome marker was used to identify donor cells. Old animals' responses varied greatly, perhaps due to suppressing cells or factors in some individuals. Therefore, cells were never pooled and the responses of receipients were compared to the responses of the donor whose marrow had populated them. The response for a particular old donor, or for the recipients of its stem cells, was divided by the response for the young control used with that donor, or for its stem cell recipients. This was called the old/young ratio. With original donors with an old/young ratio for the SRBC response of (mean  +/- S.D.) 0.35 +/- 0.14, The old/young ratio for that same response in the recipients was significantly improved to 1.26 +/- 0.71. In original donors with an old/young ratio for the PHA response of 0.44 +/- 0.17, the old/young ratio in the recipients improved significantly to 0.86 +/- 0.27. Thus, little or none of the decline with age in these immune responses was intrinsic to the old lymphoid stem cells."}
{"id": "PMID:15034", "title": "The allogeneic effect on tumor growth. I. Inhibition of a murine plasmacytoma, MOPC 315, by the graft-vs-host reaction.", "content": "The allogeneic effect has been employed as a potent immunopotentiator in preventing the growth of a murine plasmacytoma and prolonging host survival. Parental BALB/c spleen cells were passively transferred to (BALB/c x A/H)F1 hybrid mice, who were then given a highly lethal dose of MOPC 315 plasmacytoma, a tumor of BALB/c origin. The resultant graft-vs-host reaction protected the recipient mice against growth of the tumor and significantly prolonged survival. This phenomenon was dependent upon the dose of BALB/c lymphoid cells employed, the route of administration, and the time interval between lymphoid cell transfer and tumor inoculation. A wide range of lymphoid cell doses and time intervals were effective, and repeated doses of allogeneic cells provided better protection than a single dose.", "contents": "The allogeneic effect on tumor growth. I. Inhibition of a murine plasmacytoma, MOPC 315, by the graft-vs-host reaction. The allogeneic effect has been employed as a potent immunopotentiator in preventing the growth of a murine plasmacytoma and prolonging host survival. Parental BALB/c spleen cells were passively transferred to (BALB/c x A/H)F1 hybrid mice, who were then given a highly lethal dose of MOPC 315 plasmacytoma, a tumor of BALB/c origin. The resultant graft-vs-host reaction protected the recipient mice against growth of the tumor and significantly prolonged survival. This phenomenon was dependent upon the dose of BALB/c lymphoid cells employed, the route of administration, and the time interval between lymphoid cell transfer and tumor inoculation. A wide range of lymphoid cell doses and time intervals were effective, and repeated doses of allogeneic cells provided better protection than a single dose."}
{"id": "PMID:15035", "title": "The allogeneic effect on tumor growth. II. Suppression of both ascitic and solid MOPC 315 plasmacytoma by the graft-vs-host reaction, with pathologic correlation.", "content": "The growth of an ascitic murine plasmacytoma, MOPC 315, can be retarded in CAF1 hybrid host mice by the i.p. injection of donor lymphoid cells. The graft-vs-host reaction can be established by a variety of donor cells, including parental BALB/c and A/J and congenic inbred B10.D2 which share the major histocompatibility locus with BALB/c(H-2d). Optimal results are consistently obtained when parental BALB/c spleen cells are injected before tumor inoculation, and a second dose of donor spleen cells injected 1 week later. This aloogeneic effect on tumor growth is manifested by delayed appearance of the tumor and prolonged host survival. Pathologic studies on the ascites tumor indicated that the allogeneic effect suppresses the initial appearance and early growth of the plasmacytoma. However, once established, MOPC 315 grows rapidly and fatally in both control mice and recipients of donor lymphoid cells. Further, a subcutaneous implant of MOPC 315 is suppressed by an allogeneic effect established either i.v. with BALB/c spleen cells before tumor inoculation or by BALB/c spleen cells administered subcutaneously at the time of MOPC 315 implant. Thirty percent of mice treated by i.v. or subcutaneous donor lymphoid cells were tumor free at 150 days after tumor inoculation.", "contents": "The allogeneic effect on tumor growth. II. Suppression of both ascitic and solid MOPC 315 plasmacytoma by the graft-vs-host reaction, with pathologic correlation. The growth of an ascitic murine plasmacytoma, MOPC 315, can be retarded in CAF1 hybrid host mice by the i.p. injection of donor lymphoid cells. The graft-vs-host reaction can be established by a variety of donor cells, including parental BALB/c and A/J and congenic inbred B10.D2 which share the major histocompatibility locus with BALB/c(H-2d). Optimal results are consistently obtained when parental BALB/c spleen cells are injected before tumor inoculation, and a second dose of donor spleen cells injected 1 week later. This aloogeneic effect on tumor growth is manifested by delayed appearance of the tumor and prolonged host survival. Pathologic studies on the ascites tumor indicated that the allogeneic effect suppresses the initial appearance and early growth of the plasmacytoma. However, once established, MOPC 315 grows rapidly and fatally in both control mice and recipients of donor lymphoid cells. Further, a subcutaneous implant of MOPC 315 is suppressed by an allogeneic effect established either i.v. with BALB/c spleen cells before tumor inoculation or by BALB/c spleen cells administered subcutaneously at the time of MOPC 315 implant. Thirty percent of mice treated by i.v. or subcutaneous donor lymphoid cells were tumor free at 150 days after tumor inoculation."}
{"id": "PMID:15036", "title": "Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin.", "content": "Mouse spleen cells could be preparatively separated into immunoglobulin positive (Ig+) and immunoglobulin-netative (Ig-)populations by incubating as many as 2 X 10(8) cells per 100 mm diameter petri plate coated with specifically purified goat anti-mouse immunoglobulin. The non-adherent population was 95% or more Ig-, and possessed graft versus host and cytotoxic effector activities, as would be expected for T cells. They could also give a mixed lymphocyte reaction and generate cytotoxic effector activity on culture in vitro. The adherent cells could not be released undamaged from plates coated with undiluted anti-Ig, but they could be released from plates coated with a 1/4 or 1/10 dilution of anti-Ig in an irrelevant antibody. The released cells were over 90% viable by trypan-blue staining, and 94% or more of the viable cells were Ig+.", "contents": "Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. Mouse spleen cells could be preparatively separated into immunoglobulin positive (Ig+) and immunoglobulin-netative (Ig-)populations by incubating as many as 2 X 10(8) cells per 100 mm diameter petri plate coated with specifically purified goat anti-mouse immunoglobulin. The non-adherent population was 95% or more Ig-, and possessed graft versus host and cytotoxic effector activities, as would be expected for T cells. They could also give a mixed lymphocyte reaction and generate cytotoxic effector activity on culture in vitro. The adherent cells could not be released undamaged from plates coated with undiluted anti-Ig, but they could be released from plates coated with a 1/4 or 1/10 dilution of anti-Ig in an irrelevant antibody. The released cells were over 90% viable by trypan-blue staining, and 94% or more of the viable cells were Ig+."}
{"id": "PMID:15037", "title": "Immunochemical and morphological studies of hepatitis B core antigen isolated from the nuclei of hepatocytes.", "content": "Immunochemical and morphological properties of hepatitis B core antigen (HBc Ag) were studied in intranuclear particles isolated from human liver. Immunochemical integrity of the purified particles was indicated in the production by guinea pigs of antibody to HBc Ag (anti-HBc) that was immunochemically identical to human anti-HBc. The HBc Ag particles were 27-30 nm in diameter, displayed apparent icosahedral symmetry, and consisted of distinct subunits. The susceptibility of HBc Ag particles to proteolytic and glycolytic enzymes indicated the presence of proteins and glycoproteins. The structural integrity of core particles depended on disulfide, hydrophobic, and hydrogen bonds, and immunological activity relied on intact sulfhydryl groups. Agents active against lipids did not affect immunological reactivity or core structure, as seen by electron microscopy.", "contents": "Immunochemical and morphological studies of hepatitis B core antigen isolated from the nuclei of hepatocytes. Immunochemical and morphological properties of hepatitis B core antigen (HBc Ag) were studied in intranuclear particles isolated from human liver. Immunochemical integrity of the purified particles was indicated in the production by guinea pigs of antibody to HBc Ag (anti-HBc) that was immunochemically identical to human anti-HBc. The HBc Ag particles were 27-30 nm in diameter, displayed apparent icosahedral symmetry, and consisted of distinct subunits. The susceptibility of HBc Ag particles to proteolytic and glycolytic enzymes indicated the presence of proteins and glycoproteins. The structural integrity of core particles depended on disulfide, hydrophobic, and hydrogen bonds, and immunological activity relied on intact sulfhydryl groups. Agents active against lipids did not affect immunological reactivity or core structure, as seen by electron microscopy."}
{"id": "PMID:15038", "title": "Effect of atherosclerosis on lysosomal cholesterol esterase activity in rabbit aorta.", "content": "Radiolabeled cholesteryl oleate, when incorporated into phospholipid vesicles, was hydrolyzed at acid pH by an enzyme present in rabbit aortic homogenates. In contrast, cholesteryl oleate presented as an acetone dispersion was not effectively hydrolyzed at acid pH under identical conditions. Using the vesicle preparation as substrate, a sensitive assay system for the acid hydrolase was developed in which hydrolysis was proportional to protein concentration and incubation time, and was independent of substrate concentration. The physical state of the vesicles was apparently not altered by the assay conditions, and no hydrolysis of the vesicle-associated phospholipid was detected. Acid cholesterol esterase activity in atherosclerotic aortic tissue was 2.5-fold greater than that of control tissue, and even greater increases were observed in the activities of other lysosomal enzymes (N-acetyl-beta-d-glucosaminidase and beta-glucuronidase). Glucose-6-phosphatase activity was also increased in aortas from cholesterol-fed animals while 5' nucleotidase activity remained unchanged. Labeled triolein also was incorporated into phospholipid vesicles and was hydrolyzed by an acid lipase in aortic tissue. Similarities between triolein and cholesteryl oleate hydrolysis existed with respect to pH optimum and the effect of cholesterol feeding on activity, suggesting that a single enzyme may hydrolyze both lipids.", "contents": "Effect of atherosclerosis on lysosomal cholesterol esterase activity in rabbit aorta. Radiolabeled cholesteryl oleate, when incorporated into phospholipid vesicles, was hydrolyzed at acid pH by an enzyme present in rabbit aortic homogenates. In contrast, cholesteryl oleate presented as an acetone dispersion was not effectively hydrolyzed at acid pH under identical conditions. Using the vesicle preparation as substrate, a sensitive assay system for the acid hydrolase was developed in which hydrolysis was proportional to protein concentration and incubation time, and was independent of substrate concentration. The physical state of the vesicles was apparently not altered by the assay conditions, and no hydrolysis of the vesicle-associated phospholipid was detected. Acid cholesterol esterase activity in atherosclerotic aortic tissue was 2.5-fold greater than that of control tissue, and even greater increases were observed in the activities of other lysosomal enzymes (N-acetyl-beta-d-glucosaminidase and beta-glucuronidase). Glucose-6-phosphatase activity was also increased in aortas from cholesterol-fed animals while 5' nucleotidase activity remained unchanged. Labeled triolein also was incorporated into phospholipid vesicles and was hydrolyzed by an acid lipase in aortic tissue. Similarities between triolein and cholesteryl oleate hydrolysis existed with respect to pH optimum and the effect of cholesterol feeding on activity, suggesting that a single enzyme may hydrolyze both lipids."}
{"id": "PMID:15039", "title": "[Mathematical simulation of the respiratory system (author's transl)].", "content": "The respiratory system is described as a feedback control system. The controller consists of the peripheral chemoreceptors and the central chemosensitive structures, the respiratory centre in the medulla oblongata and the thorax-lung pump which they drive. The controlled system is comprised of three compartments (lung, brain and the remaining tissue) connected by the blood circulation. The controlled values are arterial pH and arterial O2 partial pressure and cerebral extracellular pH. Earlier models have been improved by: (1) the dead space description, (2) the thermodynamic formulation of the CO2 dissociation equation and the simple but accurate O2 dissociation equation of the blood, (3) the alteration of the CO2 dissociation equation for the brain and the remaining tissue to accommodate recent results, (4) the application of the one-receptor-theory of central chemosensitivity, (5) the pH dependence of brain circulation, (6) the bicarbonate exchange between blood and extracellular fluid of the brain and (7) the introduction of variable circulation times. Respiratory and metabolic disturbances of the respiratory system are analyzed. The mathematical formulation of the respiratory system is a differential difference equation system. In the steady state the experimental results are reproduced fairly well. A slight discrepancy is found in the simulation of metabolic acidosis. Apparently we have assumed the sensitivity of the peripheral chemoreceptors to be too large so that the respiratory response is not correctly predicted. In the numerical solution there is an overshoot in the on-transient and a damped oscillation in the off-transient of the alveolar CO2 partial pressure during respiratory acidosis. We have varied the parameters to make deviations small. The best agreement seems to result, if the central threshold is near the normal extracellular pH of the brain. A further deviation from experimental findings is that the cerebral CO2 and H+ concentration, the blood circulation of the brain, the alveolar O2 partial tension and the ventilation show a slight oscillation in the off-transient. Except for these discrepancies the experimental results, especially the stability of the extracellular pH of the brain, are reproduced fairly well. During hypoxia there are deviations form the experimental results if the central residual activity is constant and the central threshold deviates from the normal extracellular pH of the brain. But if the central residual activity is pH dependent and if the central threshold is equal to the normal extracellular pH of the brain, then the time course of VE and the other variables agree fairly well with experimental results. There is also a good correspondence between the theoretical and experimental data during hyperoxia. During metabolic acidosis the time constant of the bicarbonate exchange between blood and extracellular fluid of the brain is important. If a time constant of one minute is assumed, then the predicted and the experimental results correspond sufficiently well.", "contents": "[Mathematical simulation of the respiratory system (author's transl)]. The respiratory system is described as a feedback control system. The controller consists of the peripheral chemoreceptors and the central chemosensitive structures, the respiratory centre in the medulla oblongata and the thorax-lung pump which they drive. The controlled system is comprised of three compartments (lung, brain and the remaining tissue) connected by the blood circulation. The controlled values are arterial pH and arterial O2 partial pressure and cerebral extracellular pH. Earlier models have been improved by: (1) the dead space description, (2) the thermodynamic formulation of the CO2 dissociation equation and the simple but accurate O2 dissociation equation of the blood, (3) the alteration of the CO2 dissociation equation for the brain and the remaining tissue to accommodate recent results, (4) the application of the one-receptor-theory of central chemosensitivity, (5) the pH dependence of brain circulation, (6) the bicarbonate exchange between blood and extracellular fluid of the brain and (7) the introduction of variable circulation times. Respiratory and metabolic disturbances of the respiratory system are analyzed. The mathematical formulation of the respiratory system is a differential difference equation system. In the steady state the experimental results are reproduced fairly well. A slight discrepancy is found in the simulation of metabolic acidosis. Apparently we have assumed the sensitivity of the peripheral chemoreceptors to be too large so that the respiratory response is not correctly predicted. In the numerical solution there is an overshoot in the on-transient and a damped oscillation in the off-transient of the alveolar CO2 partial pressure during respiratory acidosis. We have varied the parameters to make deviations small. The best agreement seems to result, if the central threshold is near the normal extracellular pH of the brain. A further deviation from experimental findings is that the cerebral CO2 and H+ concentration, the blood circulation of the brain, the alveolar O2 partial tension and the ventilation show a slight oscillation in the off-transient. Except for these discrepancies the experimental results, especially the stability of the extracellular pH of the brain, are reproduced fairly well. During hypoxia there are deviations form the experimental results if the central residual activity is constant and the central threshold deviates from the normal extracellular pH of the brain. But if the central residual activity is pH dependent and if the central threshold is equal to the normal extracellular pH of the brain, then the time course of VE and the other variables agree fairly well with experimental results. There is also a good correspondence between the theoretical and experimental data during hyperoxia. During metabolic acidosis the time constant of the bicarbonate exchange between blood and extracellular fluid of the brain is important. If a time constant of one minute is assumed, then the predicted and the experimental results correspond sufficiently well."}
{"id": "PMID:15040", "title": "Enzymic changes in the cervix of the rat and hamster during the oestrous cycle and the effect of steroids.", "content": "Changes in four hydrolytic enzymes, namely acid phosphatase, alkaline phosphatase, arylsulphatase A and B, of the cervix of the rat and hamster have been studied during the 4-day oestrous cycle. All four enzymes showed maximal activity on the day of oestrus and least activity on day 2 of dioestrus. All the enzymes showed significant reduction of activity after ovariectomy, arylsulphatase A and B showing the earliest changes in specific activity. A single subcutaneous injection of 0-02 microng oestradiol-17beta/rat increased the especific activity of arylsulphatase A and B from the low ovariectomized level to that observed in control oestrous animals within 18 and 6 h respectively. A higher concentration of oestradiol 17beta (2-0 microng) had an inhibitory effect. Progesterone was without effect on arylsulphatase B activity, but when given (2-0 mg) with 0-02 microng oestradiol-17beta, it inhibited the response to oestrogen. Cycloheximide prevented the rise in arylsulphatase B activity occurring after oestrogen injection, suggesting a regulation of cervical arylsulphatase B at the level of protein biosynthesis. These results suggest that arylsulphatase B activity may be induced by oestrogen in the cervix of the rat.", "contents": "Enzymic changes in the cervix of the rat and hamster during the oestrous cycle and the effect of steroids. Changes in four hydrolytic enzymes, namely acid phosphatase, alkaline phosphatase, arylsulphatase A and B, of the cervix of the rat and hamster have been studied during the 4-day oestrous cycle. All four enzymes showed maximal activity on the day of oestrus and least activity on day 2 of dioestrus. All the enzymes showed significant reduction of activity after ovariectomy, arylsulphatase A and B showing the earliest changes in specific activity. A single subcutaneous injection of 0-02 microng oestradiol-17beta/rat increased the especific activity of arylsulphatase A and B from the low ovariectomized level to that observed in control oestrous animals within 18 and 6 h respectively. A higher concentration of oestradiol 17beta (2-0 microng) had an inhibitory effect. Progesterone was without effect on arylsulphatase B activity, but when given (2-0 mg) with 0-02 microng oestradiol-17beta, it inhibited the response to oestrogen. Cycloheximide prevented the rise in arylsulphatase B activity occurring after oestrogen injection, suggesting a regulation of cervical arylsulphatase B at the level of protein biosynthesis. These results suggest that arylsulphatase B activity may be induced by oestrogen in the cervix of the rat."}
{"id": "PMID:15041", "title": "Developmental expression and biochemical characterization Nassarius obsoleta.", "content": "Electrophoretic analysis of catalase isozyme patterns of Nassarius obsoleta indicates that these isozymes are products of two separate loci. Five aminopeptidase isozymes have also been detected in N. obsoleta and the data suggest that at least two loci encode these aminopetidase isozymes. Experiments designed to test for the interconvertibility of the isozymes indicated that the two catalase isozymes and that two of the five aminopeptidase isozymes tested were not conformational artifacts but distinct genetic products. No change in catalase isozyme expression, but considerable quantitative variation in catalase specific activity was noted during early developmental stages of N. obsoleta. Both qualitative and quantitative changes were noted in aminopeptidase expression during early developmental stages. This paper also describes several physicochemical parameters for each of the two enzymes under study.", "contents": "Developmental expression and biochemical characterization Nassarius obsoleta. Electrophoretic analysis of catalase isozyme patterns of Nassarius obsoleta indicates that these isozymes are products of two separate loci. Five aminopeptidase isozymes have also been detected in N. obsoleta and the data suggest that at least two loci encode these aminopetidase isozymes. Experiments designed to test for the interconvertibility of the isozymes indicated that the two catalase isozymes and that two of the five aminopeptidase isozymes tested were not conformational artifacts but distinct genetic products. No change in catalase isozyme expression, but considerable quantitative variation in catalase specific activity was noted during early developmental stages of N. obsoleta. Both qualitative and quantitative changes were noted in aminopeptidase expression during early developmental stages. This paper also describes several physicochemical parameters for each of the two enzymes under study."}
{"id": "PMID:15042", "title": "Physiology and chemistry of cerebrospinal fluid, aqueous humor and endolymph in Squalus acanthias.", "content": "By means of the appropriate isotopes injected into the spiny dogfish, Squalus acanthias, the transfer of all major ions into cerebrospinal fluid (CSF), aqueous humor (A) and endolymph (E) was studied. In addition, the effect of raising pCO2 in sea-water upon HCO3- concentration of these fluids was measured. In the several types of experiments, acetazolamide or methazolamide was used to inhibit completely carbonic anhydrase. The rates of fluid formation and ion transfer in CSF and A were fairly close, but those for E were far slower. The general pattern of ion transport in the three fluids were the same, Na+ (or Na+ + K+ in E) entry greater than Cl - entry, and the difference was HCO3-. The greater rate constants for HCO3-, increase in its entry rate by elevation of pCO2, and inhibition of its appearance by the sulfonamides, show that this is a special case  of transport; the ion is formed in secretory cells from gaseous CO2 + OH-. Secretory cells at sites of formation of all the fluids contain both carbonic anhydrase and Na+-K+-ATP-ase, which subserve HCO3- formation and Na+ (or K+) transport. Comparison of these results with studies in mammals show that the vertebrate pattern for secretion of these three fluids is well established in the elasmobranch.", "contents": "Physiology and chemistry of cerebrospinal fluid, aqueous humor and endolymph in Squalus acanthias. By means of the appropriate isotopes injected into the spiny dogfish, Squalus acanthias, the transfer of all major ions into cerebrospinal fluid (CSF), aqueous humor (A) and endolymph (E) was studied. In addition, the effect of raising pCO2 in sea-water upon HCO3- concentration of these fluids was measured. In the several types of experiments, acetazolamide or methazolamide was used to inhibit completely carbonic anhydrase. The rates of fluid formation and ion transfer in CSF and A were fairly close, but those for E were far slower. The general pattern of ion transport in the three fluids were the same, Na+ (or Na+ + K+ in E) entry greater than Cl - entry, and the difference was HCO3-. The greater rate constants for HCO3-, increase in its entry rate by elevation of pCO2, and inhibition of its appearance by the sulfonamides, show that this is a special case  of transport; the ion is formed in secretory cells from gaseous CO2 + OH-. Secretory cells at sites of formation of all the fluids contain both carbonic anhydrase and Na+-K+-ATP-ase, which subserve HCO3- formation and Na+ (or K+) transport. Comparison of these results with studies in mammals show that the vertebrate pattern for secretion of these three fluids is well established in the elasmobranch."}
{"id": "PMID:15043", "title": "Characterization of gill (Na + K)-activated adenosine triphosphatase from chinook salmon, Oncorhynchus tshawytscha.", "content": "(Na+K)-activated ATPase activity from gills of yearling spring chinook was examined using a new rapid assay method. Characterization of the enzyme activity was performed. Optimal activity was obtained at pH 7.2 in the presence of 240 mM NaCl, 120 mM KCl, 20 mM MgCl2 and 10 mM Na2ATP. Maximal inhibition of the enzyme was observed in the presence of 0.5 mM ouabain. Differential centrifugation indicated that 75% of the enzymatic activity was sedimented at 1000 x g. Only 8% of the activity was found in the microsomal pellet. Treatment with 0.1% sodium deoxycholate liberated activity from the 1000 x g pellet and elevated the activity. This treatment caused a loss of 20% of the original activity of the preparation. Statistical analysis of the sampling procedure for gill (Na+K)-activated ATPase activity indicated that there was small variation in the technique itself when compared to variation between the individual gill arches and between individual fish. Results indicate that for meaningful comparisons of groups of fish, the sampling of the gill arches must be standardized and a large number of individual fish must be sampled.", "contents": "Characterization of gill (Na + K)-activated adenosine triphosphatase from chinook salmon, Oncorhynchus tshawytscha. (Na+K)-activated ATPase activity from gills of yearling spring chinook was examined using a new rapid assay method. Characterization of the enzyme activity was performed. Optimal activity was obtained at pH 7.2 in the presence of 240 mM NaCl, 120 mM KCl, 20 mM MgCl2 and 10 mM Na2ATP. Maximal inhibition of the enzyme was observed in the presence of 0.5 mM ouabain. Differential centrifugation indicated that 75% of the enzymatic activity was sedimented at 1000 x g. Only 8% of the activity was found in the microsomal pellet. Treatment with 0.1% sodium deoxycholate liberated activity from the 1000 x g pellet and elevated the activity. This treatment caused a loss of 20% of the original activity of the preparation. Statistical analysis of the sampling procedure for gill (Na+K)-activated ATPase activity indicated that there was small variation in the technique itself when compared to variation between the individual gill arches and between individual fish. Results indicate that for meaningful comparisons of groups of fish, the sampling of the gill arches must be standardized and a large number of individual fish must be sampled."}
{"id": "PMID:15044", "title": "Correlation of structure and active transport in the teleost nephron.", "content": "In the present study we have extended our investigations concerning the correlation between ultrastructure and active transport in the isolated flounder nephron. The composition of the fish nephron is defined in ultrastructural terms and its behavior when incubated in vitro under short term and long term culture conditions is described. Using the in vitro system originally described by Forster, a variety of inhibitors and conditions which modify cell structure and function were tested. Ultrastructure was correlated with chlorphenol red dye transport. In general, conditions altering active transport also markedly altered cellular ultrastructure. The principal alterations consisted of membrane changes involving various organelles--most importantly the plasma membrane and the mitochondria. Conditions associated with irreversible cell injury could be rapidly produced by interference either with mitochondrial ATP synthesis or with the integrity of the plasma membrane. Both of these rapidly lead to irreversible events which are preceded by reversible structural changes. Organelle changes progress in a rather well-defined sequence of reversible and irreversible stages which are defined. One difference between the two types of interactions is the presence of intramitochondrial calcification which does not occur with direct modification of the mitochondrial electron transport system. The concept of utilizing long term explant organ cultures of fish nephrons for environmental studies is introduced.", "contents": "Correlation of structure and active transport in the teleost nephron. In the present study we have extended our investigations concerning the correlation between ultrastructure and active transport in the isolated flounder nephron. The composition of the fish nephron is defined in ultrastructural terms and its behavior when incubated in vitro under short term and long term culture conditions is described. Using the in vitro system originally described by Forster, a variety of inhibitors and conditions which modify cell structure and function were tested. Ultrastructure was correlated with chlorphenol red dye transport. In general, conditions altering active transport also markedly altered cellular ultrastructure. The principal alterations consisted of membrane changes involving various organelles--most importantly the plasma membrane and the mitochondria. Conditions associated with irreversible cell injury could be rapidly produced by interference either with mitochondrial ATP synthesis or with the integrity of the plasma membrane. Both of these rapidly lead to irreversible events which are preceded by reversible structural changes. Organelle changes progress in a rather well-defined sequence of reversible and irreversible stages which are defined. One difference between the two types of interactions is the presence of intramitochondrial calcification which does not occur with direct modification of the mitochondrial electron transport system. The concept of utilizing long term explant organ cultures of fish nephrons for environmental studies is introduced."}
{"id": "PMID:15046", "title": "Characteristics of the chloride conductance in muscle fibers of the rat diaphragm.", "content": "In muscle fibers from the rat diaphragm, 85% of the resting membrane ion conductance is attributable to Cl-. At 37 degree C and pH 7.0, GCl averages 2.11 mmho/cm2 while residual conductance largely due to K+ averages 0.34 mmho/cm2. The resting GCl exhibits a biphasic temperature dependence with a Q10 of 1.6 between 6 degree C and 25 degree C and a Q10 of nearly 1 between 25 degree C and 40 degree C. Decreasing external pH reversibly reduced GCl; the apparent pK for groups mediating this decrease is 5.5. Increasing pH up to 10.0 had no effect on GCl. Anion conductance sequence and permeability sequence were both determined to be Cl-greater than Br-greater than or equal to I-greater than CH3SO4-. Lowering the pH below 5.5 reduced the magnitude of the measured conductance to all anions but did not alter the conductance sequence. The permeability sequence was likewise unchanged at low pH. Experiments with varying molar ratios of Cl- and I- indicated a marked interaction between these ions in their transmembrane movement. Similar but less striking interaction was seen between Cl- and Br-. Current-voltage relationships for GCl measured at early time-points in the presence of Rb+ were linear, but showed marked rectification with longer hyperpolarizing pulses (greater than 50ms) due to a slow time-and voltage-dependent change in membrane conductance to Cl-. This nonlinear behavior appeared to depend on the concentration of Cl- present but cannot be attributed to tubular ion accumulation. Tubular disruption with glycerol lowers apparent GCl but not GK, suggesting that the transverse tubule (T-tubule) system is permeable to Cl- in this species. Quantitative estimates indicate that up to 80% of GCl may be associated with the T tubules.", "contents": "Characteristics of the chloride conductance in muscle fibers of the rat diaphragm. In muscle fibers from the rat diaphragm, 85% of the resting membrane ion conductance is attributable to Cl-. At 37 degree C and pH 7.0, GCl averages 2.11 mmho/cm2 while residual conductance largely due to K+ averages 0.34 mmho/cm2. The resting GCl exhibits a biphasic temperature dependence with a Q10 of 1.6 between 6 degree C and 25 degree C and a Q10 of nearly 1 between 25 degree C and 40 degree C. Decreasing external pH reversibly reduced GCl; the apparent pK for groups mediating this decrease is 5.5. Increasing pH up to 10.0 had no effect on GCl. Anion conductance sequence and permeability sequence were both determined to be Cl-greater than Br-greater than or equal to I-greater than CH3SO4-. Lowering the pH below 5.5 reduced the magnitude of the measured conductance to all anions but did not alter the conductance sequence. The permeability sequence was likewise unchanged at low pH. Experiments with varying molar ratios of Cl- and I- indicated a marked interaction between these ions in their transmembrane movement. Similar but less striking interaction was seen between Cl- and Br-. Current-voltage relationships for GCl measured at early time-points in the presence of Rb+ were linear, but showed marked rectification with longer hyperpolarizing pulses (greater than 50ms) due to a slow time-and voltage-dependent change in membrane conductance to Cl-. This nonlinear behavior appeared to depend on the concentration of Cl- present but cannot be attributed to tubular ion accumulation. Tubular disruption with glycerol lowers apparent GCl but not GK, suggesting that the transverse tubule (T-tubule) system is permeable to Cl- in this species. Quantitative estimates indicate that up to 80% of GCl may be associated with the T tubules."}
{"id": "PMID:15047", "title": "The relationship between anion exchange and net anion flow across the human red blood cell membrane.", "content": "The conductive (net) anion permeability of human red blood cells was determined from net KCl or K2SO4 effluxes into low K+ media at high valinomycin concentrations, conditions under which the salt efflux is limited primarily by the net anion permeability. Disulfonic stilbenes, inhibitors of anion exchange, also inhibited KCl or K2SO4 efflux under these conditions, but were less effective at lower valinomycin concentrations where K+ permeability is the primary limiting factor. Various concentrations of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) had similar inhibitory effects on net and exchange sulfate fluxes, both of which were almost completely DIDS sensitive. In the case of Cl-, a high correlation was also found between inhibition of net and exchange fluxes, but in this case about 35% of the net flux was insensitive to DIDS. The net and exchange transport processes differed strikingly in their anion selectivity. Net chloride permeability was only four times as high as net sulfate permeability, whereas chloride exchange is over 10,000 times faster than sulfate exchange. Net OH-permeability, determined by an analogous method, was over four orders of magnitude larger than that of Cl-, but was also sensitive to DIDS. These data and others are discussed in terms of the possibility that a common element may be involved in both net and exchange anion transport.", "contents": "The relationship between anion exchange and net anion flow across the human red blood cell membrane. The conductive (net) anion permeability of human red blood cells was determined from net KCl or K2SO4 effluxes into low K+ media at high valinomycin concentrations, conditions under which the salt efflux is limited primarily by the net anion permeability. Disulfonic stilbenes, inhibitors of anion exchange, also inhibited KCl or K2SO4 efflux under these conditions, but were less effective at lower valinomycin concentrations where K+ permeability is the primary limiting factor. Various concentrations of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) had similar inhibitory effects on net and exchange sulfate fluxes, both of which were almost completely DIDS sensitive. In the case of Cl-, a high correlation was also found between inhibition of net and exchange fluxes, but in this case about 35% of the net flux was insensitive to DIDS. The net and exchange transport processes differed strikingly in their anion selectivity. Net chloride permeability was only four times as high as net sulfate permeability, whereas chloride exchange is over 10,000 times faster than sulfate exchange. Net OH-permeability, determined by an analogous method, was over four orders of magnitude larger than that of Cl-, but was also sensitive to DIDS. These data and others are discussed in terms of the possibility that a common element may be involved in both net and exchange anion transport."}
{"id": "PMID:15048", "title": "Extrasynaptic receptors on cell bodies of neurons in central nervous system of the leech.", "content": "1. A systematic study has been made of the sensitivity of identified sensory and motoneurons in the leech central nervous system to chemical transmitter substances. 2. The following substances elicited responses from the cell bodies of individual neurons: acetylcholine, 5-hydroxytryptamine, gamma-aminobutyric acid, glutamic acid, glycine, dopamine, and norepinephrine. Since the cell bodies of leech neurons are free of synapses, the receptors that give rise to these responses are extrasynaptic. 3. Sensory and motoneurons of different function had characteristic complements of extrasynaptic receptors. For example, mechanosensory cells responding to light touch, to pressure, and to noxious stimuli could be distinguished by their responses to iontophoretically applied compounds. For one of these modalities (nociceptive), neurons with different receptive fields but otherwise similar properties had markedly distinct extrasynaptic receptors. The possible significance of extrasynaptic receptors is discussed.", "contents": "Extrasynaptic receptors on cell bodies of neurons in central nervous system of the leech. 1. A systematic study has been made of the sensitivity of identified sensory and motoneurons in the leech central nervous system to chemical transmitter substances. 2. The following substances elicited responses from the cell bodies of individual neurons: acetylcholine, 5-hydroxytryptamine, gamma-aminobutyric acid, glutamic acid, glycine, dopamine, and norepinephrine. Since the cell bodies of leech neurons are free of synapses, the receptors that give rise to these responses are extrasynaptic. 3. Sensory and motoneurons of different function had characteristic complements of extrasynaptic receptors. For example, mechanosensory cells responding to light touch, to pressure, and to noxious stimuli could be distinguished by their responses to iontophoretically applied compounds. For one of these modalities (nociceptive), neurons with different receptive fields but otherwise similar properties had markedly distinct extrasynaptic receptors. The possible significance of extrasynaptic receptors is discussed."}
{"id": "PMID:15049", "title": "Synthesis of acetylcholine by excitatory motoneurons in central nervous system of the leech.", "content": "1. A study was made of the synthesis of acetylcholine (ACh) and other transmitters by the cell bodies of functionally identified neurons in leech segmental ganglia. 2. Choline acetyltransferase, the synthetic enzyme for ACh, was detected in excitatory motoneurons but not in mechanosensory cells or Retzius cells. The ability of motoneurons to synthesize ACh was also demonstrated by their accumulation of [3H]ACh following incubation of segmental ganglia with [3H]choline. [3H]ACh was not detected in the other cell types. When eserine was included in [3H]choline incubations, the amount of [3H]ACh in motoneurons increased severalfold and small amounts of [3H]ACh (1% that in motor cells) appeared in extracts of sensory and Retzius cells. 3. In addition to [3H]ACh segmental ganglia synthesized [3H]5-HT, [3H]gamma-aminobutyric acid, [3H]dopamine, and [3H]octopamine from exogenous, labeled precursors. None of these labeled transmitters was detected in identified neurons except [3H]5-HT, which was found in Retzius cells. 4. These results provide biochemical evidence that excitatory motoneurons in the leech are cholinergic, but leave open the identity of the sensory transmitter(s).", "contents": "Synthesis of acetylcholine by excitatory motoneurons in central nervous system of the leech. 1. A study was made of the synthesis of acetylcholine (ACh) and other transmitters by the cell bodies of functionally identified neurons in leech segmental ganglia. 2. Choline acetyltransferase, the synthetic enzyme for ACh, was detected in excitatory motoneurons but not in mechanosensory cells or Retzius cells. The ability of motoneurons to synthesize ACh was also demonstrated by their accumulation of [3H]ACh following incubation of segmental ganglia with [3H]choline. [3H]ACh was not detected in the other cell types. When eserine was included in [3H]choline incubations, the amount of [3H]ACh in motoneurons increased severalfold and small amounts of [3H]ACh (1% that in motor cells) appeared in extracts of sensory and Retzius cells. 3. In addition to [3H]ACh segmental ganglia synthesized [3H]5-HT, [3H]gamma-aminobutyric acid, [3H]dopamine, and [3H]octopamine from exogenous, labeled precursors. None of these labeled transmitters was detected in identified neurons except [3H]5-HT, which was found in Retzius cells. 4. These results provide biochemical evidence that excitatory motoneurons in the leech are cholinergic, but leave open the identity of the sensory transmitter(s)."}
{"id": "PMID:15050", "title": "Filterability of erythrocytes from vitamin E-deficient lead-poisoned rats.", "content": "The time required for red blood cells (RBC) from vitamin E-deficient lead-poisoned (-E + Pb) rats to pass through polycarbonate filters after incubation in vitro was much greater than that of RBC from vitamin E-supplemented non-poisoned rats. Vitamin E deficiency per se (i.e., in non-poisoned rats) often increased filtration times, but in all such experiments the RBC from -E + Pb groups had even longer filtration times. Administration of lead to rats supplemented with vitamin E had little effect on the filtration rate of RBC. N,N'-diphenyl-p-phenylenediamine (DPPD) prevented the increased filtration times characteristic of RBC from -E + Pb rats, but replacement of the lard in the vitamin E-deficient basal diet by more highly polyunsaturated fats did not exacerbate the increased filtration times of RBC from -E + Pb rats. The increased filtration time of RBC from -E + Pb rats appeared to be related to the extent of RBC lipid peroxidation. Decreasing the pH of the RBC incubation medium from 7.4 to 6.6, an acidity typical of the spleen, markedly increased the filtration times of RBC from -E + Pb rats. Addition of lead in vitro increased filtration times of RBC from both vitamin E-deficient and supplemented non-poisoned rats, but filtration times tended to be longer in the deficient group. These results suggest that vitamin E deficiency and lead toxicity act synergistically to alter the deformability of the RBC thereby rendering it vulnerable to sequestration in the spleen.", "contents": "Filterability of erythrocytes from vitamin E-deficient lead-poisoned rats. The time required for red blood cells (RBC) from vitamin E-deficient lead-poisoned (-E + Pb) rats to pass through polycarbonate filters after incubation in vitro was much greater than that of RBC from vitamin E-supplemented non-poisoned rats. Vitamin E deficiency per se (i.e., in non-poisoned rats) often increased filtration times, but in all such experiments the RBC from -E + Pb groups had even longer filtration times. Administration of lead to rats supplemented with vitamin E had little effect on the filtration rate of RBC. N,N'-diphenyl-p-phenylenediamine (DPPD) prevented the increased filtration times characteristic of RBC from -E + Pb rats, but replacement of the lard in the vitamin E-deficient basal diet by more highly polyunsaturated fats did not exacerbate the increased filtration times of RBC from -E + Pb rats. The increased filtration time of RBC from -E + Pb rats appeared to be related to the extent of RBC lipid peroxidation. Decreasing the pH of the RBC incubation medium from 7.4 to 6.6, an acidity typical of the spleen, markedly increased the filtration times of RBC from -E + Pb rats. Addition of lead in vitro increased filtration times of RBC from both vitamin E-deficient and supplemented non-poisoned rats, but filtration times tended to be longer in the deficient group. These results suggest that vitamin E deficiency and lead toxicity act synergistically to alter the deformability of the RBC thereby rendering it vulnerable to sequestration in the spleen."}
{"id": "PMID:15051", "title": "Utilization of riboflavin homologues by D-amino acid oxidase and xanthine oxidase.", "content": "D-Amino acid oxidase and xanthine oxidase, two enzymes possessing ionically bound flavin coenzymes have been studied with their flavin coenzymes derived from either 7-ethyl-8-methyl-flavin or 7-methyl-8-ethyl-flavin, vitamin-like homologues of riboflavin. 7-Ethyl-8-methyl-flavin caused a significant reduction of both D-amino acid oxidase and xanthine oxidase in the liver, but not in the kidney. 7-Methyl-8-ethyl-flavin caused a significant reduction of D-amino acid oxidase in both the liver and kidney, a significant reduction of xanthine oxidase in the liver, but a large and significant increase of the latter enzyme in the kidney. An improved procedure for the assay of xanthine oxidase has been described.", "contents": "Utilization of riboflavin homologues by D-amino acid oxidase and xanthine oxidase. D-Amino acid oxidase and xanthine oxidase, two enzymes possessing ionically bound flavin coenzymes have been studied with their flavin coenzymes derived from either 7-ethyl-8-methyl-flavin or 7-methyl-8-ethyl-flavin, vitamin-like homologues of riboflavin. 7-Ethyl-8-methyl-flavin caused a significant reduction of both D-amino acid oxidase and xanthine oxidase in the liver, but not in the kidney. 7-Methyl-8-ethyl-flavin caused a significant reduction of D-amino acid oxidase in both the liver and kidney, a significant reduction of xanthine oxidase in the liver, but a large and significant increase of the latter enzyme in the kidney. An improved procedure for the assay of xanthine oxidase has been described."}
{"id": "PMID:15052", "title": "Beneficial effect of methionine and threonine supplements on tyrosine toxicity in rats.", "content": "The growth retardation and external pathological lesions that occur in rats fed a 10% casein diet containing 5% tyrosine could be alleviated by the supplementation of extra protein (20% casein) or 0.66% methionine plus 0.90% threonine (equivalent to the contents in a 20% casein, respectively). Liver tyrosine aminotransferase activity is elevated by ingestion of excess tyrosine, but lowered by the supplementation of extra casein of methionine plus threonine. In rats fed a high tyrosine diet supplemented with methionine plus threonine, liver p-hydroxyphenylpyruvate hydroxylase activity was not higher than that of the 10% casein group, but liver homogentisate oxidase activity increased significantly. When excess tyrosine was included in the 10% casein diet, free tyrosine concentrations in plasma, liver, muscle and brain were extremely elevated, but when the high tyrosine diet was supplemented with extra casein or methionine plus threonine, their plasma and tissues tyrosine concentrations lowered significantly. A large increase in total phenols, p-hydroxyphenylpyruvate and free tyrosine excretions in urine was produced in animals fed the high tyrosine-low protein diet, but these were lowered by the supplementation of methionine and threonine to the diet.", "contents": "Beneficial effect of methionine and threonine supplements on tyrosine toxicity in rats. The growth retardation and external pathological lesions that occur in rats fed a 10% casein diet containing 5% tyrosine could be alleviated by the supplementation of extra protein (20% casein) or 0.66% methionine plus 0.90% threonine (equivalent to the contents in a 20% casein, respectively). Liver tyrosine aminotransferase activity is elevated by ingestion of excess tyrosine, but lowered by the supplementation of extra casein of methionine plus threonine. In rats fed a high tyrosine diet supplemented with methionine plus threonine, liver p-hydroxyphenylpyruvate hydroxylase activity was not higher than that of the 10% casein group, but liver homogentisate oxidase activity increased significantly. When excess tyrosine was included in the 10% casein diet, free tyrosine concentrations in plasma, liver, muscle and brain were extremely elevated, but when the high tyrosine diet was supplemented with extra casein or methionine plus threonine, their plasma and tissues tyrosine concentrations lowered significantly. A large increase in total phenols, p-hydroxyphenylpyruvate and free tyrosine excretions in urine was produced in animals fed the high tyrosine-low protein diet, but these were lowered by the supplementation of methionine and threonine to the diet."}
{"id": "PMID:15053", "title": "Blood and brain concentrations of imipramine, clomipramine and their monomethylated metabolites after oral and intramuscular administration in rats.", "content": "Imipramine and clomipramine were administered to rats by the oral and intramuscular routes as single and multiple doses. The concentrations of both drugs and their active demethylated metabolites desipramine and desmethylclomipramine were measured in blood plasma, blood cells and brain. The concentrations of the metabolites were higher and the concentrations of the parent substances lower after oral than after parenteral administration, both in blood and in brain. In brain imipramine, despiramine and clomipramine during continuous treatment exceeded their plasma concentrations by six to ten times. The corresponding figure for desmethylclomipramine was 1-7. The extent of accumulation of the investigated substances in the brain was independent of the route of administration.", "contents": "Blood and brain concentrations of imipramine, clomipramine and their monomethylated metabolites after oral and intramuscular administration in rats. Imipramine and clomipramine were administered to rats by the oral and intramuscular routes as single and multiple doses. The concentrations of both drugs and their active demethylated metabolites desipramine and desmethylclomipramine were measured in blood plasma, blood cells and brain. The concentrations of the metabolites were higher and the concentrations of the parent substances lower after oral than after parenteral administration, both in blood and in brain. In brain imipramine, despiramine and clomipramine during continuous treatment exceeded their plasma concentrations by six to ten times. The corresponding figure for desmethylclomipramine was 1-7. The extent of accumulation of the investigated substances in the brain was independent of the route of administration."}
{"id": "PMID:15066", "title": "Papaver bracteatum Lindley: thebaine content in relation to plant development.", "content": "Four thebaine-rich varieties of P. bracteatum have been grown in the open over two seasons and the thebaine distribution in aerial parts examined to determine the most suitable source material for commercial production. The leaves contained only 0-1 to 0-15%; the capsules 0-5 to 3-0% and the bled latex 28 to 53%. The maximum for the latter occurred about 3-4 weeks after petal opening and during the day, at about 15,00 h. A product 'bractium' prepared exactly as opium from P. somniferum contained up to 55% thebaine and calculations from the 1974 results gave theoretical yields up to 58 k of thebaine per hectare. However this is a very labour intensive method; furthermore bled latex only represents about 46% of the total thebaine of the capsule. In addition the pedicels contain significant amounts of thebaine, so that fruiting tops may be recommended as source material. In the capsule the thebaine content reaches a peak 3 to 4 weeks after petal opening and again two weeks later. At this fully ripe stage there is a theoretical yield of 50 kg per hectare. Two further advantages accrue from collection at this time: the ripe seeds can probably be used for similar purposes as poppy seed; and the pericarps at this stage contain no 'bound thebaine' (i;e., thebaine insoluble in MeOH; NH4OH but soluble in acetic acid--in unripe capsules bound thebaine represents 18 to 36% of the total thebaine). There is some evidence that, as this perennial plant increases in age, the capacity for thebaine production seems to continue increasing. Storage of raw material, even in ideal conditions, led to a loss of thebaine of 12 to 20% in one year.", "contents": "Papaver bracteatum Lindley: thebaine content in relation to plant development. Four thebaine-rich varieties of P. bracteatum have been grown in the open over two seasons and the thebaine distribution in aerial parts examined to determine the most suitable source material for commercial production. The leaves contained only 0-1 to 0-15%; the capsules 0-5 to 3-0% and the bled latex 28 to 53%. The maximum for the latter occurred about 3-4 weeks after petal opening and during the day, at about 15,00 h. A product 'bractium' prepared exactly as opium from P. somniferum contained up to 55% thebaine and calculations from the 1974 results gave theoretical yields up to 58 k of thebaine per hectare. However this is a very labour intensive method; furthermore bled latex only represents about 46% of the total thebaine of the capsule. In addition the pedicels contain significant amounts of thebaine, so that fruiting tops may be recommended as source material. In the capsule the thebaine content reaches a peak 3 to 4 weeks after petal opening and again two weeks later. At this fully ripe stage there is a theoretical yield of 50 kg per hectare. Two further advantages accrue from collection at this time: the ripe seeds can probably be used for similar purposes as poppy seed; and the pericarps at this stage contain no 'bound thebaine' (i;e., thebaine insoluble in MeOH; NH4OH but soluble in acetic acid--in unripe capsules bound thebaine represents 18 to 36% of the total thebaine). There is some evidence that, as this perennial plant increases in age, the capacity for thebaine production seems to continue increasing. Storage of raw material, even in ideal conditions, led to a loss of thebaine of 12 to 20% in one year."}
{"id": "PMID:15067", "title": "Dimensional changes of compacts after compression.", "content": "A non-contact optical technique has been used to measure changes in the heights and diameters of compacts prepared from sodium chloride, spray dried lactose, two samples of methylcellulose powder and two spray-dried lactose-maize starch granulations. Both sodium chloride and spray dried lactose exhibited relatively small dimensional changes whilst the methylcellulose powders showed up to 30% axial and 3% radial expansion. The results are discussed in terms of the inherent properties of the materials. When the lactose was granulated with maize starch, the ratio of axial; radial strain recovery was reduced from 5-9:1 to approximately 1:1, suggesting an improved distribution of forces during compression of the granulations,", "contents": "Dimensional changes of compacts after compression. A non-contact optical technique has been used to measure changes in the heights and diameters of compacts prepared from sodium chloride, spray dried lactose, two samples of methylcellulose powder and two spray-dried lactose-maize starch granulations. Both sodium chloride and spray dried lactose exhibited relatively small dimensional changes whilst the methylcellulose powders showed up to 30% axial and 3% radial expansion. The results are discussed in terms of the inherent properties of the materials. When the lactose was granulated with maize starch, the ratio of axial; radial strain recovery was reduced from 5-9:1 to approximately 1:1, suggesting an improved distribution of forces during compression of the granulations,"}
{"id": "PMID:15068", "title": "Moisture and gelatin effects on the interparticle attractive forces and the compression behaviour of oxytetracycline formulations.", "content": "The tensile strengths of compacts and/or tablets of the individual components and of granules prepared from an oxytetracycline formulation have been measured using the diametral compression test. Employing the theory of tensile strength, proposed by Cheng, it has been shown that increases in both moisture and gelatin contents of compacts and tablets increase the range of the attractive forces that operate between the granules. By studying the effects of moisture and gelatin on the compressional behaviour of the granules, it has been possible to classify them into different types. Fragmentation of granules occurs at packing fractions between 0-745 and 0-835, depending on their gelatin content.", "contents": "Moisture and gelatin effects on the interparticle attractive forces and the compression behaviour of oxytetracycline formulations. The tensile strengths of compacts and/or tablets of the individual components and of granules prepared from an oxytetracycline formulation have been measured using the diametral compression test. Employing the theory of tensile strength, proposed by Cheng, it has been shown that increases in both moisture and gelatin contents of compacts and tablets increase the range of the attractive forces that operate between the granules. By studying the effects of moisture and gelatin on the compressional behaviour of the granules, it has been possible to classify them into different types. Fragmentation of granules occurs at packing fractions between 0-745 and 0-835, depending on their gelatin content."}
{"id": "PMID:15069", "title": "The properties of tablets containing microcrystalline cellulose.", "content": "Tablets have been prepared from mixtures of microcrystalline cellulose (Avicel) and spray dried lactose. Tests on these showed that a maximum value of dissolution rate occurred as the percentage of the cellulose increased. This maximum was at 4% w/w for mixtures containing Avicel PH 101 and coincided with the point of maximum liquid penetration rate. With grade PH 105 this maximum was at 2% w/w and corresponded to the optimum balance between the opposing factors of disintegration and liquid penetration rate. Addition of up to 2% w/w magnesium stearate to the formulation containing 4% w/w PH 101 grade had little effect on pore structure, but decreased the dissolution rate by retarding water penetration. Similar concentrations of Carbowax 4000 caused no such decrease.", "contents": "The properties of tablets containing microcrystalline cellulose. Tablets have been prepared from mixtures of microcrystalline cellulose (Avicel) and spray dried lactose. Tests on these showed that a maximum value of dissolution rate occurred as the percentage of the cellulose increased. This maximum was at 4% w/w for mixtures containing Avicel PH 101 and coincided with the point of maximum liquid penetration rate. With grade PH 105 this maximum was at 2% w/w and corresponded to the optimum balance between the opposing factors of disintegration and liquid penetration rate. Addition of up to 2% w/w magnesium stearate to the formulation containing 4% w/w PH 101 grade had little effect on pore structure, but decreased the dissolution rate by retarding water penetration. Similar concentrations of Carbowax 4000 caused no such decrease."}
{"id": "PMID:15070", "title": "The influence of temperature on the sorption of benzocaine by nylon 6 from aqueous cosolvents.", "content": "The influence of temperature on the sorption of benzocaine by nylon 6 powder from aqueous cosolvents has been assessed. At about 30 degrees discontinuities appear in the Van't Hoff plots for sorption from water and aqueous PEG 400, which may be attributed to transitional changes in the polymer structure. No such discontinuities are apparent for sorption from aqueous ethanol over the temperature range 15-60 degrees, which is indicative of plasticizaton by this cosolvent.", "contents": "The influence of temperature on the sorption of benzocaine by nylon 6 from aqueous cosolvents. The influence of temperature on the sorption of benzocaine by nylon 6 powder from aqueous cosolvents has been assessed. At about 30 degrees discontinuities appear in the Van't Hoff plots for sorption from water and aqueous PEG 400, which may be attributed to transitional changes in the polymer structure. No such discontinuities are apparent for sorption from aqueous ethanol over the temperature range 15-60 degrees, which is indicative of plasticizaton by this cosolvent."}
{"id": "PMID:15071", "title": "The identification and quantitation of the major metabolites of ethylamphetamine, produced by rabbit liver microsomal preparations.", "content": "Amphetamine (I), 1-phenylpropan-2-ol (III), phenylacetone (V), N-hydroxyethylamphetamine (VII), and alpha-methyl-N-(1'-phenylprop-2'-yl)nitrone (VIII) were obtained as metabolic products from the incubation of ethylamphetamine (II) with fortified male rabbit liver 9000 g supernatant fractions. These metabolites were identified by comparing their t.l.c., g,l.c. and g.l.c.-m.s. behaviour to that of reference compounds. A method for the quantitative analysis of the metabolites in mixtures using g.l.c. techniques is described.", "contents": "The identification and quantitation of the major metabolites of ethylamphetamine, produced by rabbit liver microsomal preparations. Amphetamine (I), 1-phenylpropan-2-ol (III), phenylacetone (V), N-hydroxyethylamphetamine (VII), and alpha-methyl-N-(1'-phenylprop-2'-yl)nitrone (VIII) were obtained as metabolic products from the incubation of ethylamphetamine (II) with fortified male rabbit liver 9000 g supernatant fractions. These metabolites were identified by comparing their t.l.c., g,l.c. and g.l.c.-m.s. behaviour to that of reference compounds. A method for the quantitative analysis of the metabolites in mixtures using g.l.c. techniques is described."}
{"id": "PMID:15072", "title": "Effect of oxotremorine and sodium pentobarbitone on the pharmacokinetics of intravenous tracer doses or radioactive choline.", "content": "The present study explains for the previous findings that oxotremorine increases and sodium pentobarbitone decreases the initial brain uptake of intravenously injected radioactive choline (3H-Ch). The effects are explained by haemodynamic changes since a corresponding increase and decrease in the plasma concentrations of 3H-Ch were found. This is important to know when 3H-Ch is used for estimation of aceytlcholine turnover in the brain. The drugs did not affect the distribution of radioactivity (3H) between plasma and erythrocytes.", "contents": "Effect of oxotremorine and sodium pentobarbitone on the pharmacokinetics of intravenous tracer doses or radioactive choline. The present study explains for the previous findings that oxotremorine increases and sodium pentobarbitone decreases the initial brain uptake of intravenously injected radioactive choline (3H-Ch). The effects are explained by haemodynamic changes since a corresponding increase and decrease in the plasma concentrations of 3H-Ch were found. This is important to know when 3H-Ch is used for estimation of aceytlcholine turnover in the brain. The drugs did not affect the distribution of radioactivity (3H) between plasma and erythrocytes."}
{"id": "PMID:15073", "title": "The fate of prostaglandin A1-5,6-3H in the rat.", "content": "The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43% of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin;", "contents": "The fate of prostaglandin A1-5,6-3H in the rat. The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43% of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin;"}
{"id": "PMID:15074", "title": "Possible subdivisions among alpha-adrenoreceptors in various isolated tissues.", "content": "The ratio (expressed in log10 units) of the equieffective concentrations of (+)- and (-)-noradrenaline has been measured in a variety of isolated tissues in the presence of cocaine (1 x 10(-5) M), tropolone (3 x 10(-5) M) and (+/-)-propranolol (5 x 10(-7) to 5 x 10(-5) M). The values obtained fall into 3 distinct and statistically different groups. Firstly, a high group comprising (mean +/- s.e.) mouse vasdeferens (2-78 +/- 0-04), rabbit duodenum (2-91 +/- 0-07) and ileum (2-86 +/- 0-05). Secondly a middle group comprising rabbit vas deferens (2-54 +/- 0-04), bladder neck muscle (2-56 +/- 0-07) and spleen 2-50 +/- 0-02), guinea-pig vas deferens (2-55 +/- 0-10) and bladder neck muscle (2-48 +/- 0-13) and rat deferens (2-40 +/- 0-08) and thirdlya low group comprising the bladder detrusor muscle from both the rabbit (2-08 +/- 0-08) and the guinea-pig (2-07 +/- 0-04). Under the same conditions measurement of pA2 values for phentolamine and piperoxan against noradrenaline gave the following values in rat vase deferens (8-22 +/- 0-07 and 6-72 +/- 0-03 respectively) and mouse vas deferens (8-31 +/- 0-05 and 6-53 +/- 0-07 respectively). The results are discussed in relation to other findings conderning the nature of the alpha-adrenoreceptor in these tissues. In spite of the absence of any significant difference between the potency of the alpha-adrenoreceptor blocking agents in the two species it is suggested that alpha-adernoreceptors may not belong to a single homogenous population but may vary in their characteristics from tissue to tissue.", "contents": "Possible subdivisions among alpha-adrenoreceptors in various isolated tissues. The ratio (expressed in log10 units) of the equieffective concentrations of (+)- and (-)-noradrenaline has been measured in a variety of isolated tissues in the presence of cocaine (1 x 10(-5) M), tropolone (3 x 10(-5) M) and (+/-)-propranolol (5 x 10(-7) to 5 x 10(-5) M). The values obtained fall into 3 distinct and statistically different groups. Firstly, a high group comprising (mean +/- s.e.) mouse vasdeferens (2-78 +/- 0-04), rabbit duodenum (2-91 +/- 0-07) and ileum (2-86 +/- 0-05). Secondly a middle group comprising rabbit vas deferens (2-54 +/- 0-04), bladder neck muscle (2-56 +/- 0-07) and spleen 2-50 +/- 0-02), guinea-pig vas deferens (2-55 +/- 0-10) and bladder neck muscle (2-48 +/- 0-13) and rat deferens (2-40 +/- 0-08) and thirdlya low group comprising the bladder detrusor muscle from both the rabbit (2-08 +/- 0-08) and the guinea-pig (2-07 +/- 0-04). Under the same conditions measurement of pA2 values for phentolamine and piperoxan against noradrenaline gave the following values in rat vase deferens (8-22 +/- 0-07 and 6-72 +/- 0-03 respectively) and mouse vas deferens (8-31 +/- 0-05 and 6-53 +/- 0-07 respectively). The results are discussed in relation to other findings conderning the nature of the alpha-adrenoreceptor in these tissues. In spite of the absence of any significant difference between the potency of the alpha-adrenoreceptor blocking agents in the two species it is suggested that alpha-adernoreceptors may not belong to a single homogenous population but may vary in their characteristics from tissue to tissue."}
{"id": "PMID:15075", "title": "Effect of butaclamol, a new neuroleptic, on serotoninergic mechanisms.", "content": "Butaclamol (1.0-0.1 mg kg-1, i.p.) and spiroperidol (1-0-0-5 mg kg-1, i.p.) but not (-)-butaclamol (15 mg kg-1, i.p.), blocked the hyperactivity induced in rats by tranylcypromine-L-tryptophan pretreatment. Neither butaclamol nor spiroperidol altered the accumulation of brain 5-HT following parglyine or the decline of brain 5-HT following inhibition with the tryptophan hydroxylase inhibitor alpha-propyldopacetamide thus indicating that butaclamol and spiroperidol do not affect either the synthesis or the turnover of brain 5-HT. It is concluded that the antagonism of the tranylcypromise-L-tryptophan-induced hyperactivity by butaclamol and spiroperidol is due to their blockade of dopaminergic receptors rather than an action on neuronal serotoninergic mechanisms.", "contents": "Effect of butaclamol, a new neuroleptic, on serotoninergic mechanisms. Butaclamol (1.0-0.1 mg kg-1, i.p.) and spiroperidol (1-0-0-5 mg kg-1, i.p.) but not (-)-butaclamol (15 mg kg-1, i.p.), blocked the hyperactivity induced in rats by tranylcypromine-L-tryptophan pretreatment. Neither butaclamol nor spiroperidol altered the accumulation of brain 5-HT following parglyine or the decline of brain 5-HT following inhibition with the tryptophan hydroxylase inhibitor alpha-propyldopacetamide thus indicating that butaclamol and spiroperidol do not affect either the synthesis or the turnover of brain 5-HT. It is concluded that the antagonism of the tranylcypromise-L-tryptophan-induced hyperactivity by butaclamol and spiroperidol is due to their blockade of dopaminergic receptors rather than an action on neuronal serotoninergic mechanisms."}
{"id": "PMID:15076", "title": "Effect of lofepramine and other antidepressants on the uptake of 5-hydroxytryptamine and noradrenaline into rat brain monoaminergic neurons.", "content": "Lofepramine, (N-methyl-N-[4-chlorobenzoylmethyl]-3-[10,11-dihydro-5H-dibenz(b,f)-azepin-5-yl]-propylamine hydrochloride), is a new antidepressant with low toxicity and no peripheral anticholinergic activity. Its effect on 5-hydroxytryptamine (5-HT) and noradrenaline uptake into rat brain monoaminergic neurons was studied and compared with that of other antidepressants, particularly with that of imipramine and desipramine. Lofepramine inhibited both 5-HT and noradrenaline uptake into synaptosomal fractions in vitro but was 4 times more potent in inhibiting noradrenaline than 5-HT uptake, indicating the effect resembles that of desipramine. Noradrenaline uptake was also preferentially inhibited in synaptosomes from brain of rats treated previously with lofepramine or desipramine (i.p.). Pretreatment with SKF 525A (i.p.) did not diminish the effect of lofepramine, but rather potentiated it. Therefore it is suggested that the formation of desipramine is not necessary for lofepramine to exhibit, the effect on amine uptake in vivo. Both lofepramine and desipramine inhibited intraventricular noradrenaline uptake into synaptosomes without any effect on 5-HT uptake. These results suggest that lofepramine is qualitatively similar to desipramine with respect to preferential inhibition of noradrenaline uptake into central noradrenergic neurons.", "contents": "Effect of lofepramine and other antidepressants on the uptake of 5-hydroxytryptamine and noradrenaline into rat brain monoaminergic neurons. Lofepramine, (N-methyl-N-[4-chlorobenzoylmethyl]-3-[10,11-dihydro-5H-dibenz(b,f)-azepin-5-yl]-propylamine hydrochloride), is a new antidepressant with low toxicity and no peripheral anticholinergic activity. Its effect on 5-hydroxytryptamine (5-HT) and noradrenaline uptake into rat brain monoaminergic neurons was studied and compared with that of other antidepressants, particularly with that of imipramine and desipramine. Lofepramine inhibited both 5-HT and noradrenaline uptake into synaptosomal fractions in vitro but was 4 times more potent in inhibiting noradrenaline than 5-HT uptake, indicating the effect resembles that of desipramine. Noradrenaline uptake was also preferentially inhibited in synaptosomes from brain of rats treated previously with lofepramine or desipramine (i.p.). Pretreatment with SKF 525A (i.p.) did not diminish the effect of lofepramine, but rather potentiated it. Therefore it is suggested that the formation of desipramine is not necessary for lofepramine to exhibit, the effect on amine uptake in vivo. Both lofepramine and desipramine inhibited intraventricular noradrenaline uptake into synaptosomes without any effect on 5-HT uptake. These results suggest that lofepramine is qualitatively similar to desipramine with respect to preferential inhibition of noradrenaline uptake into central noradrenergic neurons."}
{"id": "PMID:15077", "title": "Hyperpyrexic interaction between debrisoquine and pethidine in rabbits.", "content": "Pethidine injection into rabbits treated with debrisoquine either acutely or chronically resulted in severe interaction and fatal hyperpyrexia. Pretreatment of rabbits with p-chlorophenylalanine, chlorpromazine, or crypoheptadine protected them against the interaction, while alpha-methyl-p-tyrosine was ineffective. In addition the administration of debrisoquine into 5-HTP pretreated rabbits produced a severe interaction and hyperpyrexia. The hepatic N-demethylation of pethidine was significantly inhibited by debrisoquine pretreatment both in vivo and in vitro. The debrisoquine-pethidine interaction could be due to 5-HT potentiation or prevention of uptake. Alternatively it could be due to inhibition of biotransformation of pethidine by debrisoquine. However, neither mechanism by itself alone could be held responsible as the sole explanation of the interaction.", "contents": "Hyperpyrexic interaction between debrisoquine and pethidine in rabbits. Pethidine injection into rabbits treated with debrisoquine either acutely or chronically resulted in severe interaction and fatal hyperpyrexia. Pretreatment of rabbits with p-chlorophenylalanine, chlorpromazine, or crypoheptadine protected them against the interaction, while alpha-methyl-p-tyrosine was ineffective. In addition the administration of debrisoquine into 5-HTP pretreated rabbits produced a severe interaction and hyperpyrexia. The hepatic N-demethylation of pethidine was significantly inhibited by debrisoquine pretreatment both in vivo and in vitro. The debrisoquine-pethidine interaction could be due to 5-HT potentiation or prevention of uptake. Alternatively it could be due to inhibition of biotransformation of pethidine by debrisoquine. However, neither mechanism by itself alone could be held responsible as the sole explanation of the interaction."}
{"id": "PMID:15078", "title": "Synthesis and pharmacological properties of a series of antidopaminergic piperidyl benzamides.", "content": "The synthesis and pharmacological screening for anti-apomorphine, stomach emptying and local anaesthetic activities of some new piperidylbenzamides is described. One of these, N-(1'-benzyl-4'-piperidyl)-2-methoxy-4-amino-5-chlorobenzamide (clebopride) is more potent than metoclopramide in tests related to blockade of cerebral dopamine receptors.", "contents": "Synthesis and pharmacological properties of a series of antidopaminergic piperidyl benzamides. The synthesis and pharmacological screening for anti-apomorphine, stomach emptying and local anaesthetic activities of some new piperidylbenzamides is described. One of these, N-(1'-benzyl-4'-piperidyl)-2-methoxy-4-amino-5-chlorobenzamide (clebopride) is more potent than metoclopramide in tests related to blockade of cerebral dopamine receptors."}
{"id": "PMID:15079", "title": "Conformational analysis of dopamine by the INDO molecular orbital method.", "content": "The results of INDO calculations on dopamine are reported. A conformational energy map and an isodistance map for the key distances N-OH1, N-OH2 in dopamine as functions of the two main torsion angles tau1 and tau2 were constructed. In addition to the three known minima of dopamine corresponding to the trans and gauche forms, two new minima were found. The key distances of the rigid analogues of dopamine, apomorphine, isoapomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and isoquinoline were plotted on the isodistance map of dopamine. By taking the corresponding tau values as coordinates on the energy map, conformations of dopamine, resembling the rigid analogues, could be found. When a conformation is close to a local minimum it is assumed that this conformation is energetically favourable. The possible relation between the energy minima and the biological action of dopamine is discussed. An explanation is suggested for the lack of dopaminergic activity of isoapomorphine.", "contents": "Conformational analysis of dopamine by the INDO molecular orbital method. The results of INDO calculations on dopamine are reported. A conformational energy map and an isodistance map for the key distances N-OH1, N-OH2 in dopamine as functions of the two main torsion angles tau1 and tau2 were constructed. In addition to the three known minima of dopamine corresponding to the trans and gauche forms, two new minima were found. The key distances of the rigid analogues of dopamine, apomorphine, isoapomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and isoquinoline were plotted on the isodistance map of dopamine. By taking the corresponding tau values as coordinates on the energy map, conformations of dopamine, resembling the rigid analogues, could be found. When a conformation is close to a local minimum it is assumed that this conformation is energetically favourable. The possible relation between the energy minima and the biological action of dopamine is discussed. An explanation is suggested for the lack of dopaminergic activity of isoapomorphine."}
{"id": "PMID:15080", "title": "Structure and rheology of cetomacrogol creams: the influence of alcohol chain length and homologue composition.", "content": "Liquid paraffin-in-water emulsions prepared with cetomacrogol 1000 and alcohols cetostearyl (A), cetyl (B), steryl (C) and myristyl (D) were examined by microscopical, particle size analytical and rheological (continuous shear, small strain creep, and oscillation) techniques at 25 degrees as they aged over 30 days. The particle sizes of the emulsions were similar and did not increase significantly with age. Thus the rheological stabilities were not correlated with particle size distributors, but rather with viscoelastic networks formed in the continuous phases when the non-ionic mixed emulsifiers interacted with water. The rheological properties of emulsions B and D differed from those of emulsion C. Emulsion A, of mixed homologue composition, showed some properties similar to each of the pure alcohol emulsions. Emulsions B and D were semi-solid immediately after preparation whereas emulsion C was so mobile initially that small strain data were not derived. On ageing, the consistencies of B and D changed slightly initially, and then remained essentially constant. In contrast, the consistency of emulsion C increased on ageing, especially over the first few days when there was a change from mobile liquid to semisolid. Emulsion A was a semisolid initially but like emulsion C increased in consistency especially over the first 24 h. Continuous shear data indicated that this emulsion was the most resistant to structure breakdown. Microscopical examination supported the view that the networks formed in emulsion A were the most extensive and that stearyl alcohol networks in C formed comparatively slowly. Although the cetomacrogol/pure alcohol networks were diffuse and sometimes crystallized, they did not rapidly disintegrate on storage as did the ionic surfactant/pure alcohol networks examined previously.", "contents": "Structure and rheology of cetomacrogol creams: the influence of alcohol chain length and homologue composition. Liquid paraffin-in-water emulsions prepared with cetomacrogol 1000 and alcohols cetostearyl (A), cetyl (B), steryl (C) and myristyl (D) were examined by microscopical, particle size analytical and rheological (continuous shear, small strain creep, and oscillation) techniques at 25 degrees as they aged over 30 days. The particle sizes of the emulsions were similar and did not increase significantly with age. Thus the rheological stabilities were not correlated with particle size distributors, but rather with viscoelastic networks formed in the continuous phases when the non-ionic mixed emulsifiers interacted with water. The rheological properties of emulsions B and D differed from those of emulsion C. Emulsion A, of mixed homologue composition, showed some properties similar to each of the pure alcohol emulsions. Emulsions B and D were semi-solid immediately after preparation whereas emulsion C was so mobile initially that small strain data were not derived. On ageing, the consistencies of B and D changed slightly initially, and then remained essentially constant. In contrast, the consistency of emulsion C increased on ageing, especially over the first few days when there was a change from mobile liquid to semisolid. Emulsion A was a semisolid initially but like emulsion C increased in consistency especially over the first 24 h. Continuous shear data indicated that this emulsion was the most resistant to structure breakdown. Microscopical examination supported the view that the networks formed in emulsion A were the most extensive and that stearyl alcohol networks in C formed comparatively slowly. Although the cetomacrogol/pure alcohol networks were diffuse and sometimes crystallized, they did not rapidly disintegrate on storage as did the ionic surfactant/pure alcohol networks examined previously."}
{"id": "PMID:15081", "title": "Pharmaceutical suspensions: micro electrophoretic properties.", "content": "The microelectrophoretic properties of the drugs griseofulvin, betamethasone, nalidixic acid and thiabendazole in aqueous dispersion have been examined and the zeta potentials calculated from the measured mobilities. Variation in magnitude of particle charge with pH of dispersion is reported and related to the chemical structure and the surface characteristics. The effect of adding anionic (sodium dodecyl sulphate) cationic (dodecyl trimethyl bromide) and non-ionic (polyoxyethylene glycol monoethers of hexadecanol) surface-active agents, and mixtures of these ionic and non-ionic species, on the electrophoretic properties of the drug dispersions has been measured. The results reported agree with those found previously for a model polystyrene latex suspension system under the same conditions.", "contents": "Pharmaceutical suspensions: micro electrophoretic properties. The microelectrophoretic properties of the drugs griseofulvin, betamethasone, nalidixic acid and thiabendazole in aqueous dispersion have been examined and the zeta potentials calculated from the measured mobilities. Variation in magnitude of particle charge with pH of dispersion is reported and related to the chemical structure and the surface characteristics. The effect of adding anionic (sodium dodecyl sulphate) cationic (dodecyl trimethyl bromide) and non-ionic (polyoxyethylene glycol monoethers of hexadecanol) surface-active agents, and mixtures of these ionic and non-ionic species, on the electrophoretic properties of the drug dispersions has been measured. The results reported agree with those found previously for a model polystyrene latex suspension system under the same conditions."}
{"id": "PMID:15082", "title": "Dissolution from tablets prepared using ethyl cellulose microcapsules.", "content": "Microcapsules containing sodium phenobartitone cores in ethyl cellulose have been used to prepare tablets at from 3-9 to 358-9 MPa compression pressures. The tensile strength of these tablets is related linearly to the core: wall ratio and to the microcapsule size. Dissolution of the drug from the microcapsules, is also related to the core:wall ratio and microcapsule size, but except at low compression pressures is almost independent of the pressure used during preparation. The tablet matrix remains intact during the dissolution and the equations developed by Schwartz, Simonelli & Higuchi (1968) are followed. Large microcapsules 1:2 core: wall ratio produce friable tablets with rapid release of contents.", "contents": "Dissolution from tablets prepared using ethyl cellulose microcapsules. Microcapsules containing sodium phenobartitone cores in ethyl cellulose have been used to prepare tablets at from 3-9 to 358-9 MPa compression pressures. The tensile strength of these tablets is related linearly to the core: wall ratio and to the microcapsule size. Dissolution of the drug from the microcapsules, is also related to the core:wall ratio and microcapsule size, but except at low compression pressures is almost independent of the pressure used during preparation. The tablet matrix remains intact during the dissolution and the equations developed by Schwartz, Simonelli & Higuchi (1968) are followed. Large microcapsules 1:2 core: wall ratio produce friable tablets with rapid release of contents."}
{"id": "PMID:15093", "title": "Cognitive processes mediating behavioral change.", "content": "The present experiment was designed to test the theory that psychological procedures achieve changes in behavior by altering the level and strength of self-efficacy. In this formulation, perceived self-efficacy. In this formulation, perceived self-efficacy influences level of performance by enhancing intensity and persistence of effort. Adult phobics were administered treatments based upon either performance mastery experiences, vicarious experiences., or they received no treatment. Their efficacy expectations and approach behavior toward threats differing on a similarity dimension were measured before and after treatment. In accord with our prediction, the mastery-based treatment produced higher, stronger, and more generalized expectations of personal efficacy than did the treatment relying solely upon vicarious experiences. Results of a microanalysis further confirm the hypothesized relationship between self-efficacy and behavioral change. Self-efficacy was a uniformly accurate predictor of performance on tasks of varying difficulty with different threats regardless of whether the changes in self-efficacy were produced through enactive mastery or by vicarious experience alone.", "contents": "Cognitive processes mediating behavioral change. The present experiment was designed to test the theory that psychological procedures achieve changes in behavior by altering the level and strength of self-efficacy. In this formulation, perceived self-efficacy. In this formulation, perceived self-efficacy influences level of performance by enhancing intensity and persistence of effort. Adult phobics were administered treatments based upon either performance mastery experiences, vicarious experiences., or they received no treatment. Their efficacy expectations and approach behavior toward threats differing on a similarity dimension were measured before and after treatment. In accord with our prediction, the mastery-based treatment produced higher, stronger, and more generalized expectations of personal efficacy than did the treatment relying solely upon vicarious experiences. Results of a microanalysis further confirm the hypothesized relationship between self-efficacy and behavioral change. Self-efficacy was a uniformly accurate predictor of performance on tasks of varying difficulty with different threats regardless of whether the changes in self-efficacy were produced through enactive mastery or by vicarious experience alone."}
{"id": "PMID:15095", "title": "Oxidative reactions of hydroxylated chlorpromazine metabolites.", "content": "The oxidation pathways of two hydroxylated chlorpromazine metabolites were investigated using modern electrochemical techniques. Upon oxidation, the 7-hydroxy derivative of chlorpromazine rapidly reacts to form the 7,8-dihydroxy derivative and a substituted quinone. The oxidation potentials for both compounds were determined in the pH 3-8 range. The importance of these redox reactions and potentials to the pharmacology of the materials is discussed.", "contents": "Oxidative reactions of hydroxylated chlorpromazine metabolites. The oxidation pathways of two hydroxylated chlorpromazine metabolites were investigated using modern electrochemical techniques. Upon oxidation, the 7-hydroxy derivative of chlorpromazine rapidly reacts to form the 7,8-dihydroxy derivative and a substituted quinone. The oxidation potentials for both compounds were determined in the pH 3-8 range. The importance of these redox reactions and potentials to the pharmacology of the materials is discussed."}
{"id": "PMID:15096", "title": "Electrochemical analysis of the cephalosporin cefamandole nafate.", "content": "The polarographic assays for cefamandole sodium and its formyl ester, cefamandole nafate, are described. Controlled potential coulometry is used as an absolute method for the assignment of purity of these compounds without the need for a reference material. The precision, accuracy, and selectivity of these assays were better than for the microbiological autoturbidimetric and automated iodometric assays. NMR, TLC, GC, and polarography are used to detect and quantitate likely impurities and degradation products.", "contents": "Electrochemical analysis of the cephalosporin cefamandole nafate. The polarographic assays for cefamandole sodium and its formyl ester, cefamandole nafate, are described. Controlled potential coulometry is used as an absolute method for the assignment of purity of these compounds without the need for a reference material. The precision, accuracy, and selectivity of these assays were better than for the microbiological autoturbidimetric and automated iodometric assays. NMR, TLC, GC, and polarography are used to detect and quantitate likely impurities and degradation products."}
{"id": "PMID:15097", "title": "Tyrosine hydroxylase: delayed activation in central noradrenergic neurons and induction in adrenal medulla elicited by stimulation of central cholinergic receptors.", "content": "The centrally active muscarinic agonist, oxotremorine, elicited an up to 2-fold dose-dependent (0.25-1.5 mg/kg) increase in the activity of tyrosine hydroxylase (TH) in the rat nucleus locus coeruleus (LC) and adrenal medulla. The response occurred in LC after 24 to 48 hours and in adrenal medulla by 4 to 8 hours, peaked in LC at 72 hours and adrenal medulla at 16 to 24 hours and persisted up to 2 weeks in both tissues. In brain the effect appeared confined to cell bodies of noradrenergic neurons. The activity of dopamine beta-hydroxylase increased in adrenal medulla (40%) but not in brain. Immunotitration with anti-TH serum demonstrated that the increase of TH activity in LC is due to increased catalytic activity (activation), whereas in adrenal medulla it is due to a transynaptically mediated accumulation of enzyme protein (induction). Physostigmine (1.0 mg/kg), pilocarpine (25-50 mg/kg) and nicotine (10 mg/kg) increased TH activity in LC and adrenal. We conclude that stimulation of central cholinergic receptors of the muscarinic type results in a delayed and protracted activaiton of TH but not of dopamine beta-hydroxylase in cell bodies of central noradrenergic neurons, and reflexly, to transynaptic induction of TH and dopamine beta-hydroxylase in the adrenal medulla.", "contents": "Tyrosine hydroxylase: delayed activation in central noradrenergic neurons and induction in adrenal medulla elicited by stimulation of central cholinergic receptors. The centrally active muscarinic agonist, oxotremorine, elicited an up to 2-fold dose-dependent (0.25-1.5 mg/kg) increase in the activity of tyrosine hydroxylase (TH) in the rat nucleus locus coeruleus (LC) and adrenal medulla. The response occurred in LC after 24 to 48 hours and in adrenal medulla by 4 to 8 hours, peaked in LC at 72 hours and adrenal medulla at 16 to 24 hours and persisted up to 2 weeks in both tissues. In brain the effect appeared confined to cell bodies of noradrenergic neurons. The activity of dopamine beta-hydroxylase increased in adrenal medulla (40%) but not in brain. Immunotitration with anti-TH serum demonstrated that the increase of TH activity in LC is due to increased catalytic activity (activation), whereas in adrenal medulla it is due to a transynaptically mediated accumulation of enzyme protein (induction). Physostigmine (1.0 mg/kg), pilocarpine (25-50 mg/kg) and nicotine (10 mg/kg) increased TH activity in LC and adrenal. We conclude that stimulation of central cholinergic receptors of the muscarinic type results in a delayed and protracted activaiton of TH but not of dopamine beta-hydroxylase in cell bodies of central noradrenergic neurons, and reflexly, to transynaptic induction of TH and dopamine beta-hydroxylase in the adrenal medulla."}
{"id": "PMID:15098", "title": "Regulation of catecholamine biosynthesis in a transplantable rat pheochromocytoma.", "content": "Cells prepared from a transplantable rat pheochromocytoma synthesize norepinephrine from 14C-tyrosine, at a rate of 9.4 +/- 0.5 pml/min/mg of protein, in vitro. Incubation of the cells in a medium containing 56 mM K+ results in a 2- to 6-fold increase in norepinephrine synthesis. This increase in norepinephrine synthesis is dependent upon the presence of Ca++ in the incubation medium. Stimulation of the cells by 56 mM K+ increases the conversion of tyrosine to dopa in the presence of brocresine (an inhibitor of aromatic L-amino acid decarboxylase), and has no effect on the conversion of 3H-dopa to norepinephrine. Cells can be depleted of up to 70% of their catecholamine stores by prior incubation in 56 mM K+. Norepinephrine synthesis in catecholamine-depleted cells incubated under control conditions in only slightly (20-40%) greater than it is in nondepleted cells. However, 56 mM K+ PRODUCES A SIMILAR INCREASE IN NOREPINEPHRINE SYNTHESIS IN DEPLETED CELLS AS IT DOES IN NONDEPLETED CELLS. Inhibition of amine oxidase (flavin containing) by preincubaiton with pargyline does not greatly affect catecholamine synthesis. Incubation of the cells in 56 mMK+ results in an increase in tyrosine 3-monooxygenase activity. These results indicate that the depletion of catecholamine stores plays only a minor role in the increase in norepinephrine synthesis caused by the stimulation of chromaffin cells and suggest that the activation of tyrosine 3-monooxygenase plays a more important role in this phenomenon.", "contents": "Regulation of catecholamine biosynthesis in a transplantable rat pheochromocytoma. Cells prepared from a transplantable rat pheochromocytoma synthesize norepinephrine from 14C-tyrosine, at a rate of 9.4 +/- 0.5 pml/min/mg of protein, in vitro. Incubation of the cells in a medium containing 56 mM K+ results in a 2- to 6-fold increase in norepinephrine synthesis. This increase in norepinephrine synthesis is dependent upon the presence of Ca++ in the incubation medium. Stimulation of the cells by 56 mM K+ increases the conversion of tyrosine to dopa in the presence of brocresine (an inhibitor of aromatic L-amino acid decarboxylase), and has no effect on the conversion of 3H-dopa to norepinephrine. Cells can be depleted of up to 70% of their catecholamine stores by prior incubation in 56 mM K+. Norepinephrine synthesis in catecholamine-depleted cells incubated under control conditions in only slightly (20-40%) greater than it is in nondepleted cells. However, 56 mM K+ PRODUCES A SIMILAR INCREASE IN NOREPINEPHRINE SYNTHESIS IN DEPLETED CELLS AS IT DOES IN NONDEPLETED CELLS. Inhibition of amine oxidase (flavin containing) by preincubaiton with pargyline does not greatly affect catecholamine synthesis. Incubation of the cells in 56 mMK+ results in an increase in tyrosine 3-monooxygenase activity. These results indicate that the depletion of catecholamine stores plays only a minor role in the increase in norepinephrine synthesis caused by the stimulation of chromaffin cells and suggest that the activation of tyrosine 3-monooxygenase plays a more important role in this phenomenon."}
{"id": "PMID:15099", "title": "Differential inhibition of lipolysis in human adipose tissue by adrenergic beta receptor blocking drugs.", "content": "The effects of various adrenergic beta receptor agonists and antagonists on lipolysis (measured as glycerol release) in human adipose tissue in vitro were studied. Of the agonists investigated, the potency rank order was isoproteronol greater than norepinephrine greater than salbutamol. Adrenergic beta receptor blocking drugs inhibited catecholamineinduced lipolysis  competitively. Propranolol was the overall most effective compound, followed by metoprolol, alprenolol and practolol, whereas butoxamine and H35/25 were weak inhibitors. The results indicate that the adrenergic reciptor mediating lipolysis in human adipose tissue is of type beta-1. Basal and theophylline-induced lipolysis was reduced when higher concentrations of these drug were used.", "contents": "Differential inhibition of lipolysis in human adipose tissue by adrenergic beta receptor blocking drugs. The effects of various adrenergic beta receptor agonists and antagonists on lipolysis (measured as glycerol release) in human adipose tissue in vitro were studied. Of the agonists investigated, the potency rank order was isoproteronol greater than norepinephrine greater than salbutamol. Adrenergic beta receptor blocking drugs inhibited catecholamineinduced lipolysis  competitively. Propranolol was the overall most effective compound, followed by metoprolol, alprenolol and practolol, whereas butoxamine and H35/25 were weak inhibitors. The results indicate that the adrenergic reciptor mediating lipolysis in human adipose tissue is of type beta-1. Basal and theophylline-induced lipolysis was reduced when higher concentrations of these drug were used."}
{"id": "PMID:15100", "title": "Alterations in brain cyclic guanosine 3':5'-monophosphate levels after acute and chronic treatment with ethanol.", "content": "A previous finding from our laboratory, that a single dose of ethanol depletes cerebellar cyclic guanosine 3':5'-monophosphate (cGMP), has now been extended to an investigation of the effects of acute and chronic ethanol treatment of cGMP levels in six areas of the rat brain. Rats were either gavaged with a single dose of ethanol (6g/kg) or rendered ethanol-dependent with 11 to 15 g/kg/day in 3 to 5 fractions over a 4-day period. A single dose of ethanol depleted cGMP levels in only five areas of the brain studied. In the two areas in which a time course of the response was determined, the caudate nucleus and cerebral cortex, cGMP depletion was maximal 1 hour after ethanol administration when blood ethanol concentrations were highest. cGMP levels returned to control values as blood ethanol was eliminated. Inethanol-dependent animals still intoxicated, cGMP was reduced but not to the same magnitude in the cerebellum and brain stem when compared with the response obtained after a single dose at equivalent blood ethanol concentrations. During the ethanol withdrawal syndrome cGMP levels had returned to control vlaues. The data suggest that cBMP depletion may play a role in ethanol-induced intoxication and that tolerance to this effect develops concurrently with behavioral tolerance.", "contents": "Alterations in brain cyclic guanosine 3':5'-monophosphate levels after acute and chronic treatment with ethanol. A previous finding from our laboratory, that a single dose of ethanol depletes cerebellar cyclic guanosine 3':5'-monophosphate (cGMP), has now been extended to an investigation of the effects of acute and chronic ethanol treatment of cGMP levels in six areas of the rat brain. Rats were either gavaged with a single dose of ethanol (6g/kg) or rendered ethanol-dependent with 11 to 15 g/kg/day in 3 to 5 fractions over a 4-day period. A single dose of ethanol depleted cGMP levels in only five areas of the brain studied. In the two areas in which a time course of the response was determined, the caudate nucleus and cerebral cortex, cGMP depletion was maximal 1 hour after ethanol administration when blood ethanol concentrations were highest. cGMP levels returned to control values as blood ethanol was eliminated. Inethanol-dependent animals still intoxicated, cGMP was reduced but not to the same magnitude in the cerebellum and brain stem when compared with the response obtained after a single dose at equivalent blood ethanol concentrations. During the ethanol withdrawal syndrome cGMP levels had returned to control vlaues. The data suggest that cBMP depletion may play a role in ethanol-induced intoxication and that tolerance to this effect develops concurrently with behavioral tolerance."}
{"id": "PMID:15101", "title": "Effect of palytoxin on membrane and potential and current of frog myelinated fibers.", "content": "Palytoxin is a highly toxic compound isolated form several zoanthid Palythoa species. The effects of palytoxin on the nodal membrane of frog myelinated fiber have been studied under current clamp and under voltage clamp conditions. Under current clamp conditions, palytoxin (0.1 microng/ml, 3 x 10(-8)M) induces a depolarization which is not reversed by washing. The resting potential reaches a value of -35 mV after 10 minutes. During the same period, the evoked action potential shows a gradual decline and finally disapears after about 30 minutes. The membrane depolarization is suppressed by removal of Na ions from the external medium, but only slightly diminished when tetrodotoxin (10(-6)M) is subsequently added to the external medium. When the potential of the nodal membrane is maintained at -70 mV, palytoxin (0.1 microng/ml) causes the appearance of an inward current that increases in magnitude during 30 minutes before attaining a steady-state value. The kinetics of development of that current is modified in the presence of tetrodotoxin or saxitoxin. Voltage clamp analysis shows that palytoxin causes an increase of the resting sodium permeability that is accompanied by a shift of the voltage dependence of the transient sodium permeability in the direction of membrane hyperpolarization. The shift in the voltage dependence of the transient permeability is accompanied by a decrease of the peak transient permeability. A similar shift in the potential dependence of the sodium inactivation is observed. During and after the application of palytoxin, the internal sodium concentration increases. The steady-state (potassium) conductance is also decreased at the same time as the leak current is increasing.", "contents": "Effect of palytoxin on membrane and potential and current of frog myelinated fibers. Palytoxin is a highly toxic compound isolated form several zoanthid Palythoa species. The effects of palytoxin on the nodal membrane of frog myelinated fiber have been studied under current clamp and under voltage clamp conditions. Under current clamp conditions, palytoxin (0.1 microng/ml, 3 x 10(-8)M) induces a depolarization which is not reversed by washing. The resting potential reaches a value of -35 mV after 10 minutes. During the same period, the evoked action potential shows a gradual decline and finally disapears after about 30 minutes. The membrane depolarization is suppressed by removal of Na ions from the external medium, but only slightly diminished when tetrodotoxin (10(-6)M) is subsequently added to the external medium. When the potential of the nodal membrane is maintained at -70 mV, palytoxin (0.1 microng/ml) causes the appearance of an inward current that increases in magnitude during 30 minutes before attaining a steady-state value. The kinetics of development of that current is modified in the presence of tetrodotoxin or saxitoxin. Voltage clamp analysis shows that palytoxin causes an increase of the resting sodium permeability that is accompanied by a shift of the voltage dependence of the transient sodium permeability in the direction of membrane hyperpolarization. The shift in the voltage dependence of the transient permeability is accompanied by a decrease of the peak transient permeability. A similar shift in the potential dependence of the sodium inactivation is observed. During and after the application of palytoxin, the internal sodium concentration increases. The steady-state (potassium) conductance is also decreased at the same time as the leak current is increasing."}
{"id": "PMID:15102", "title": "Active form of ketamine in squid giant axons.", "content": "The active form of ketamine has been studied with internally perfused squid qiant axons. The drug was applied internally, and decreases in peak transient and steady-state conductances as measured by voltage clamp technique were taken as an index of activity. When the total internal ketamine concentration was maintained constant, the suppression peak transient and steady-state conductances decreased with an increase in internal pH from 7.0 TO 8.4. When the concentration of the internally present charged form of ketamine was kept constant, the suppression of the peak transient conductance remained almost constant at internal pH values of 7.0, 7.3 and 7.7, but increased at pH 8.4. However, the suppression of the stead-state conductance became more prominent as the pH was raised from 7.0 to 8.4. With a constant internal concentration of the uncharged form, the suppression of both conductances decreased as the pH was raised from 7.0 to 8.4. Computation of dissociation constants to suppretamine is more potent than the charged form at all internal pH values examined. These data also show that the potency to suppress the peak transient conductance by the charged and uncharged forms of ketamine decreased as the intertance of the charged form increased, and that of the uncharged form decreased considerably with increase in the internal pH.", "contents": "Active form of ketamine in squid giant axons. The active form of ketamine has been studied with internally perfused squid qiant axons. The drug was applied internally, and decreases in peak transient and steady-state conductances as measured by voltage clamp technique were taken as an index of activity. When the total internal ketamine concentration was maintained constant, the suppression peak transient and steady-state conductances decreased with an increase in internal pH from 7.0 TO 8.4. When the concentration of the internally present charged form of ketamine was kept constant, the suppression of the peak transient conductance remained almost constant at internal pH values of 7.0, 7.3 and 7.7, but increased at pH 8.4. However, the suppression of the stead-state conductance became more prominent as the pH was raised from 7.0 to 8.4. With a constant internal concentration of the uncharged form, the suppression of both conductances decreased as the pH was raised from 7.0 to 8.4. Computation of dissociation constants to suppretamine is more potent than the charged form at all internal pH values examined. These data also show that the potency to suppress the peak transient conductance by the charged and uncharged forms of ketamine decreased as the intertance of the charged form increased, and that of the uncharged form decreased considerably with increase in the internal pH."}
{"id": "PMID:15103", "title": "Uptake of uric acid by separated renal tubules of the rabbit. I. Characteristics of transport.", "content": "A rapid filtration procedure was used to determine rates of uric acid uptake by a preparation of separated renal cortical tubules of the rabbit. The rate of uric acid uptake was temperature dependent and showed saturation kinetics with a K of 3.2 mM. The uptake was 50% lower when measured under nitrogen as compared with uptake under oxygen. The uptake rate increased with increasing sodium concentration and decreased with increasing potassium concentration. Uptake was stimulated by citrate, succinate and pyruvate, and inhibited by alpha-ketoglutarate. Parathyroid hormone and 10(-4) M adenosine 3':5'-monophosphate increased the uric acid uptake rate when preincubated with the tubules for 130 minutes before the addition of uric acid. Uric acid uptake in this preparation appears to occur by some form of carrier-mediated active transport.", "contents": "Uptake of uric acid by separated renal tubules of the rabbit. I. Characteristics of transport. A rapid filtration procedure was used to determine rates of uric acid uptake by a preparation of separated renal cortical tubules of the rabbit. The rate of uric acid uptake was temperature dependent and showed saturation kinetics with a K of 3.2 mM. The uptake was 50% lower when measured under nitrogen as compared with uptake under oxygen. The uptake rate increased with increasing sodium concentration and decreased with increasing potassium concentration. Uptake was stimulated by citrate, succinate and pyruvate, and inhibited by alpha-ketoglutarate. Parathyroid hormone and 10(-4) M adenosine 3':5'-monophosphate increased the uric acid uptake rate when preincubated with the tubules for 130 minutes before the addition of uric acid. Uric acid uptake in this preparation appears to occur by some form of carrier-mediated active transport."}
{"id": "PMID:15104", "title": "Further evaluation of the discriminative effects of morphine in the rat.", "content": "Rats were trained in a two-choice discrete trial avoidance paradigm to discriminate between saline and 3.0 mg/kg of morphine. Behavior was considered to be under stimulus ocntrol when the rats completed at least 90% of the trials in a 20-trial session on the morphine-appropriate choice lever after receiving morphine and when they completed at least 90% of the trials on the saline-appropriate choice lever after receiving saline. The discriminative effects of morphine, measured by responding on the morphine-appropriate lever, were then evaluated by determining the dose-response characteristics of representative narcotic analgesics, analgesics with mixed agonist and narcotic antagonist properties and nonopioid psychoactive drugs. Eight narcotic analgesics each produced dose-related responding on the morphine-appropriate lever. The relative potency for producing discriminative effects equivalent to those produced by 3.0 mg/kg of morphine ranged form etonitazene = 1000 x morphine to propoxyphene = 0.0175 x morphine. Of the narcotic antagonist analgesics tested, butorphanol and nalmexone produced discriminative effects equivalent to those of the morphine training dose whereas nalorphine, levallorphan, oxilorphan, nalbuphine and ketocyclazocine did not. The nonopioid psychoactive drugs, mescaline, ketamine, physostigmine and scopolamine, also failed to produce discriminative effect equivalent to those produced by 3.0 mg/kg of morphine. These results confirm and extend our previous findings that of those drugs which have also been evaluated in man, discriminative effects equivalent to the training dose of morphine are produced uniquely by narcotic analgesics and narcotic antagonists which produce morphine-like subjective effects. These results are compatible with the hypothesis that the properties of morphine which enable it to function as a discriminative stimulus in the rat are analogous to those responsible for producing subjective effects in man.", "contents": "Further evaluation of the discriminative effects of morphine in the rat. Rats were trained in a two-choice discrete trial avoidance paradigm to discriminate between saline and 3.0 mg/kg of morphine. Behavior was considered to be under stimulus ocntrol when the rats completed at least 90% of the trials in a 20-trial session on the morphine-appropriate choice lever after receiving morphine and when they completed at least 90% of the trials on the saline-appropriate choice lever after receiving saline. The discriminative effects of morphine, measured by responding on the morphine-appropriate lever, were then evaluated by determining the dose-response characteristics of representative narcotic analgesics, analgesics with mixed agonist and narcotic antagonist properties and nonopioid psychoactive drugs. Eight narcotic analgesics each produced dose-related responding on the morphine-appropriate lever. The relative potency for producing discriminative effects equivalent to those produced by 3.0 mg/kg of morphine ranged form etonitazene = 1000 x morphine to propoxyphene = 0.0175 x morphine. Of the narcotic antagonist analgesics tested, butorphanol and nalmexone produced discriminative effects equivalent to those of the morphine training dose whereas nalorphine, levallorphan, oxilorphan, nalbuphine and ketocyclazocine did not. The nonopioid psychoactive drugs, mescaline, ketamine, physostigmine and scopolamine, also failed to produce discriminative effect equivalent to those produced by 3.0 mg/kg of morphine. These results confirm and extend our previous findings that of those drugs which have also been evaluated in man, discriminative effects equivalent to the training dose of morphine are produced uniquely by narcotic analgesics and narcotic antagonists which produce morphine-like subjective effects. These results are compatible with the hypothesis that the properties of morphine which enable it to function as a discriminative stimulus in the rat are analogous to those responsible for producing subjective effects in man."}
{"id": "PMID:15105", "title": "Discriminative effects of morphine in the squirrel monkey.", "content": "Squirrel monkeys were trained in a two-choice discrete trial avoidance task to discriminate between intramuscular injections of saline and 3.0 mg/kg of morphine. Morphine (0.1-10 mg/kg) produced a dose-related increase in the number of trials completed on the morphine-appropriate lever. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) morphine-like stimulus control was produced by all other narcotic analgesics tested (fentanyl, oxymorphone, levorphanol, methadone and meperidine); 2) in so doing, these drugs spanned a 900-fold potency range relative to morphine; 3) stimulus control was blocked by the specific narcotic antagonist naloxone; and 4) stereospecificity was a requirement for stimulus control--levorphanol produced stimulus control equivalent to 3.0 mg/kg of mrophine but its optical isomer dextrorphan did not. The time course of the stimulus control produced by 3.0 mg/kg of morphine showed that the animals continued to respond on the morphine-appropriate lever up to 14 hours after morphine administration. In contrast, monkeys administered 0.01 mg/kg of fentanyl responded on the morphine lever for only as lone as 1/2 hour after fentanyl administration. Naloxone, d-amphetamine and pentobarbital all failed to substitute for morphine, Thus, this study has extended previous observations of the discriminative properties of morphine in rats by demonstrating that qualitatively similar data are produced in a second species, the squirrel monkey.", "contents": "Discriminative effects of morphine in the squirrel monkey. Squirrel monkeys were trained in a two-choice discrete trial avoidance task to discriminate between intramuscular injections of saline and 3.0 mg/kg of morphine. Morphine (0.1-10 mg/kg) produced a dose-related increase in the number of trials completed on the morphine-appropriate lever. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) morphine-like stimulus control was produced by all other narcotic analgesics tested (fentanyl, oxymorphone, levorphanol, methadone and meperidine); 2) in so doing, these drugs spanned a 900-fold potency range relative to morphine; 3) stimulus control was blocked by the specific narcotic antagonist naloxone; and 4) stereospecificity was a requirement for stimulus control--levorphanol produced stimulus control equivalent to 3.0 mg/kg of mrophine but its optical isomer dextrorphan did not. The time course of the stimulus control produced by 3.0 mg/kg of morphine showed that the animals continued to respond on the morphine-appropriate lever up to 14 hours after morphine administration. In contrast, monkeys administered 0.01 mg/kg of fentanyl responded on the morphine lever for only as lone as 1/2 hour after fentanyl administration. Naloxone, d-amphetamine and pentobarbital all failed to substitute for morphine, Thus, this study has extended previous observations of the discriminative properties of morphine in rats by demonstrating that qualitatively similar data are produced in a second species, the squirrel monkey."}
{"id": "PMID:15108", "title": "Control of hepatic and intestinal blood flow: effect of isovolaemic haemodilution on blood flow and oxygen uptake in the intact liver and intestines.", "content": "1. Limited isovolaemic haemodilution was produced in cats by addition of dextran 75-Ringer solution to an extracorporeal blood reservoir connected in series with the cat. Total hepatic venous outflow was neasured using a hepatic venous long-circuit and hepatic arterial flow was measured with an electromagnetic flow probe. Oxygen uptake was monitored in the guts and liver. Na-pentobarbitone anaesthesia was used. 2. Following reduction of the haematocrit (from 31 to 22) the oxygen uptake of the gut segment and liver were maintained. Gut conductance increased to 125% of control while the oxygen extraction ratio increased to only 109%. The hepatic arterial conductance did not change in spite of a greatly reduced (to 68%) oxygen delivery. Hepatic extraction increased to 140% of control. 3. The hepatic artery did not dilate to maintain constant oxygen supply to the liver thus confirming our previous observation that blood flow is not coupled to hepatic metabolism. 4. Oxygen extraction in the gut correlated well with changes in portal blood flow but not with changes in vascular conductance, arterial blood pressure or oxygen delivery. 5. The blood flow of the gut (vascular beds draining into the portal vein in the splenectomized preparation) was controlled in a manner that prevented changes in portal venous PO2 in spite of a reduction in oxygen content. Local PO2 and perhaps pH, are suggested as the factors controlling gut blood flow following haemodilution. 6. Changes in portal blood flow correlated with changes in portal vascular (intrahepatic) conductance such that increased portal flow produced an increased portal conductance thereby maintaining portal venous pressure constant.", "contents": "Control of hepatic and intestinal blood flow: effect of isovolaemic haemodilution on blood flow and oxygen uptake in the intact liver and intestines. 1. Limited isovolaemic haemodilution was produced in cats by addition of dextran 75-Ringer solution to an extracorporeal blood reservoir connected in series with the cat. Total hepatic venous outflow was neasured using a hepatic venous long-circuit and hepatic arterial flow was measured with an electromagnetic flow probe. Oxygen uptake was monitored in the guts and liver. Na-pentobarbitone anaesthesia was used. 2. Following reduction of the haematocrit (from 31 to 22) the oxygen uptake of the gut segment and liver were maintained. Gut conductance increased to 125% of control while the oxygen extraction ratio increased to only 109%. The hepatic arterial conductance did not change in spite of a greatly reduced (to 68%) oxygen delivery. Hepatic extraction increased to 140% of control. 3. The hepatic artery did not dilate to maintain constant oxygen supply to the liver thus confirming our previous observation that blood flow is not coupled to hepatic metabolism. 4. Oxygen extraction in the gut correlated well with changes in portal blood flow but not with changes in vascular conductance, arterial blood pressure or oxygen delivery. 5. The blood flow of the gut (vascular beds draining into the portal vein in the splenectomized preparation) was controlled in a manner that prevented changes in portal venous PO2 in spite of a reduction in oxygen content. Local PO2 and perhaps pH, are suggested as the factors controlling gut blood flow following haemodilution. 6. Changes in portal blood flow correlated with changes in portal vascular (intrahepatic) conductance such that increased portal flow produced an increased portal conductance thereby maintaining portal venous pressure constant."}
{"id": "PMID:15109", "title": "The measurement of distortion: theoretical considerations.", "content": "When very find measurements are recorded for the purpose of establishing distortion values, from the standpoint of accuracy, specific procedures must be developed. In the procedural system defined here, a potential major source of error is indicated and the means of overcoming this error established. From the standpoint of modern electronic technology, the use of an analogue-to-digital interface with a digital computer is considered extremely advantageous and allows the utilization of technical help to carry out the preliminary measurements. Under these circumstances, major error sources, such as reader error and calculation error, are eliminated. Further, multiple readings on each point can be made without significant sacrifice of time. This latter statement can help define the reading accuracy on each point and allows an immediate further set of readings on any point that has a large variation in the initially established set of readings. The applicability of this approach to any system in which an accurate set of readings is required to define distortion or some other parameter is limited only by the imagination of the investigator. Measuring points can be established at any desired location, and the number required is a function of the mathematical analysis being attempted. The use of a digital computer to compute the final values allows an immediate remeasurement of the initial values if necessary, since the computer response time is of the order of seconds for the calculations carried out. This is very important if changes in the experimental setup are likely to occur with time. In general, a computerized scheme such as is proposed here allows the investigator to concentrate on the experiment rather than the calculation of results. Also, the use of technical help to carry out delicate measuring procedures can allow the investigator more time to analyze the final results.", "contents": "The measurement of distortion: theoretical considerations. When very find measurements are recorded for the purpose of establishing distortion values, from the standpoint of accuracy, specific procedures must be developed. In the procedural system defined here, a potential major source of error is indicated and the means of overcoming this error established. From the standpoint of modern electronic technology, the use of an analogue-to-digital interface with a digital computer is considered extremely advantageous and allows the utilization of technical help to carry out the preliminary measurements. Under these circumstances, major error sources, such as reader error and calculation error, are eliminated. Further, multiple readings on each point can be made without significant sacrifice of time. This latter statement can help define the reading accuracy on each point and allows an immediate further set of readings on any point that has a large variation in the initially established set of readings. The applicability of this approach to any system in which an accurate set of readings is required to define distortion or some other parameter is limited only by the imagination of the investigator. Measuring points can be established at any desired location, and the number required is a function of the mathematical analysis being attempted. The use of a digital computer to compute the final values allows an immediate remeasurement of the initial values if necessary, since the computer response time is of the order of seconds for the calculations carried out. This is very important if changes in the experimental setup are likely to occur with time. In general, a computerized scheme such as is proposed here allows the investigator to concentrate on the experiment rather than the calculation of results. Also, the use of technical help to carry out delicate measuring procedures can allow the investigator more time to analyze the final results."}
{"id": "PMID:15110", "title": "Cathepsin D activity in bovine articular cartilage, synovial membrane and fluid: degradation of cartilage proteoglycans from same joint.", "content": "Cathepsin D type proteases were extracted from articular cartilage, synovial membrane, and synovial fluid from normal, adult bovine knee joints. A sensitive enzyme assay made it possible to measure protease activity in the different tissues from individual joints. Highest activity was found in the synovial membrane, while cell free synovial fluids contained comparatively low activity. The degrading effect on articular cartilage proteoglycans (PGC and PGS), isolated from the same joints, was demonstrated by gelfiltration on Sepharose columns and by viscometry. Gelfiltration profiles of incubation mixtures indicated a proteolytic effect on PGC and on PGS), at pH 3.5, in concentrations of enzyme and proteoglycans found in cartilage tissue. No effect at neutral pH was obtained despite a 100-fold increase of enzyme concentration. These findings were supported by viscometry data. The degrading effect of enzymes from all sources was completely inhibited by pepstatin.", "contents": "Cathepsin D activity in bovine articular cartilage, synovial membrane and fluid: degradation of cartilage proteoglycans from same joint. Cathepsin D type proteases were extracted from articular cartilage, synovial membrane, and synovial fluid from normal, adult bovine knee joints. A sensitive enzyme assay made it possible to measure protease activity in the different tissues from individual joints. Highest activity was found in the synovial membrane, while cell free synovial fluids contained comparatively low activity. The degrading effect on articular cartilage proteoglycans (PGC and PGS), isolated from the same joints, was demonstrated by gelfiltration on Sepharose columns and by viscometry. Gelfiltration profiles of incubation mixtures indicated a proteolytic effect on PGC and on PGS), at pH 3.5, in concentrations of enzyme and proteoglycans found in cartilage tissue. No effect at neutral pH was obtained despite a 100-fold increase of enzyme concentration. These findings were supported by viscometry data. The degrading effect of enzymes from all sources was completely inhibited by pepstatin."}
{"id": "PMID:15111", "title": "3-Halo-5,7-dimethylpyrazolo [1,5-a]pyrimidines, a nonbenzodiazepinoid class of antianxiety agents devoid of potentiation of central nervous system depressant effects of ethanol or barbiturates.", "content": "Forty derivatives (1-40) of pyrazolo[1,5-a]pyrimidine were synthesized and evaluated for antianxiety properties via gross behavioral observations in rats. Five of these compounds, including 5,7-dimethylpyrazolo[1,5-a]pyrimidine (6) and the 3-fluoro (7), 3-chloro (8), 3-bromo (9), and 3-iodo (10) derivatives, were selected for advanced evaluation. Although 6 and 7 had marginal activity, 8-10 had an anxiolytic effect in animals comparable to the clinically useful benzodiazepines, diazepam, and chlorodiazepoxide. Comparison with chlorpromazine indicated that 6-10 are probably not antipsychotic agents. These compounds also lacked activity in anticonvulsant and analgesic tests. Acute toxicity data (mouse, ip and po) indicated that 8-10 had excellent therapeutic ratios, although 10 was more poorly absorbed than 8 and 9. Further demonstration of anxiolytic efficacy was obtained by comparing the effects of 8 and 9 with the benzodiazepines in modifying provoked aggression in monkeys, rats (muricide), and fighting mice. The most remarkable observation, however, was that 8 and 9 had no effect, at the anxiolytic threshold, in potentiating the CNS depressant effects of ethanol or sodium barbital (po) in treated mice. In contrast, diazepam and chlorodiazepoxide potentiated this drug interaction effect at minimal anxiolytic doses.", "contents": "3-Halo-5,7-dimethylpyrazolo [1,5-a]pyrimidines, a nonbenzodiazepinoid class of antianxiety agents devoid of potentiation of central nervous system depressant effects of ethanol or barbiturates. Forty derivatives (1-40) of pyrazolo[1,5-a]pyrimidine were synthesized and evaluated for antianxiety properties via gross behavioral observations in rats. Five of these compounds, including 5,7-dimethylpyrazolo[1,5-a]pyrimidine (6) and the 3-fluoro (7), 3-chloro (8), 3-bromo (9), and 3-iodo (10) derivatives, were selected for advanced evaluation. Although 6 and 7 had marginal activity, 8-10 had an anxiolytic effect in animals comparable to the clinically useful benzodiazepines, diazepam, and chlorodiazepoxide. Comparison with chlorpromazine indicated that 6-10 are probably not antipsychotic agents. These compounds also lacked activity in anticonvulsant and analgesic tests. Acute toxicity data (mouse, ip and po) indicated that 8-10 had excellent therapeutic ratios, although 10 was more poorly absorbed than 8 and 9. Further demonstration of anxiolytic efficacy was obtained by comparing the effects of 8 and 9 with the benzodiazepines in modifying provoked aggression in monkeys, rats (muricide), and fighting mice. The most remarkable observation, however, was that 8 and 9 had no effect, at the anxiolytic threshold, in potentiating the CNS depressant effects of ethanol or sodium barbital (po) in treated mice. In contrast, diazepam and chlorodiazepoxide potentiated this drug interaction effect at minimal anxiolytic doses."}
{"id": "PMID:15112", "title": "Synthesis and adrenergic beta-blocking activity of some 1,3-benzodioxole derivatives.", "content": "A series of 1,3-benzodioxole derivatives was synthesized. We found four compounds (2,3,10 and 11 in Table IV) to have about the same order of beta-blocking activity as that of sotalol. In addition, it is of interest that some of the compounds (2-4) were found to have hypotensive activites, although they were about one-tenth of that of hydralazine. Sotalol did not produce any change in blood pressure, and propranolol raised the blood pressure.", "contents": "Synthesis and adrenergic beta-blocking activity of some 1,3-benzodioxole derivatives. A series of 1,3-benzodioxole derivatives was synthesized. We found four compounds (2,3,10 and 11 in Table IV) to have about the same order of beta-blocking activity as that of sotalol. In addition, it is of interest that some of the compounds (2-4) were found to have hypotensive activites, although they were about one-tenth of that of hydralazine. Sotalol did not produce any change in blood pressure, and propranolol raised the blood pressure."}
{"id": "PMID:15113", "title": "Beta-adrenoceptor studies. 2. Effects of alkyl substitution on beta-adrenoceptor blocking, antiarrhythmic, and local anesthetic activities of 1,1'-(o-phenylenedioxy)bis(3-isopropylamino-2-propanol).", "content": "A series of bis(2-hydroxy-3-isopropylaminopropyl) ethers of nuclear-substituted catechols (1-7) has been synthesized and examined in vitro for beta-adrenoceptor blocking activity, antagonism of ouabain-induced arrhythmias, and local anesthetic activity. Both tracheal and right atrial beta-adrenoceptor blocking activity are markedly decreased by alkyl substitution in position 3 of parent catechol diether 1. Substitution in position 4 still lowers the affinity to cardiac arrhythmias and local anesthetic activity increases with introduction of alkyl substituents in the 3 as well as in the 4 position. In contrast with biological activities, the partition coefficient 1-octanol-phosphate buffer, pH 7.40, of 1 did not change significantly by 3- and 4-methyl substitution. Stepwise multiple regression analyses were performed using log P or pi values in combination with pKa(m), E8, or sigma. With cardiac beta-adrenoceptor blocking activity the optimal equation contained E8 and pi parameters, tracheal activity appeared to depend mainly on the E8 parameter, whereas for antiarrhythmic and local anesthetic activities the lipophilicity of the substituents appeared to be the determinant factor.", "contents": "Beta-adrenoceptor studies. 2. Effects of alkyl substitution on beta-adrenoceptor blocking, antiarrhythmic, and local anesthetic activities of 1,1'-(o-phenylenedioxy)bis(3-isopropylamino-2-propanol). A series of bis(2-hydroxy-3-isopropylaminopropyl) ethers of nuclear-substituted catechols (1-7) has been synthesized and examined in vitro for beta-adrenoceptor blocking activity, antagonism of ouabain-induced arrhythmias, and local anesthetic activity. Both tracheal and right atrial beta-adrenoceptor blocking activity are markedly decreased by alkyl substitution in position 3 of parent catechol diether 1. Substitution in position 4 still lowers the affinity to cardiac arrhythmias and local anesthetic activity increases with introduction of alkyl substituents in the 3 as well as in the 4 position. In contrast with biological activities, the partition coefficient 1-octanol-phosphate buffer, pH 7.40, of 1 did not change significantly by 3- and 4-methyl substitution. Stepwise multiple regression analyses were performed using log P or pi values in combination with pKa(m), E8, or sigma. With cardiac beta-adrenoceptor blocking activity the optimal equation contained E8 and pi parameters, tracheal activity appeared to depend mainly on the E8 parameter, whereas for antiarrhythmic and local anesthetic activities the lipophilicity of the substituents appeared to be the determinant factor."}
{"id": "PMID:15114", "title": "Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid.", "content": "A series of S-alkanoyl and benzoyl derivatives of 3-mercaptopicolinic acid (3-MPA) was prepared and studied for hypoglycemic activity. Three alkanoyl derivatives (propionyl, pivaloyl, and 1-adamantanecarbonyl, 19-21) were prepared with increasing bulk around the thio ester bond. The benzoyl derivatives contained aromatic substituents chosen from a sigma-pi cluster chart so that the esters prepared had a wide range of electronic and solubility properties. In general, compounds with substituents which increased lipid solubility [p-chlorobenzoyl (4), p-trifluoromethylbenzoyl (6), and pivaloyl (20)] had the greatest potency at a dose of 300 mg/kg. Hydrolysis rates, measured at pH 6 and 8, indicated that in vivo breakdown to 3-MPA probably did not account for the observed hypoglycemic activity of the esters. 4, 6, and 20 were less potent than 3-MPA in comparative dose range studies.", "contents": "Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid. A series of S-alkanoyl and benzoyl derivatives of 3-mercaptopicolinic acid (3-MPA) was prepared and studied for hypoglycemic activity. Three alkanoyl derivatives (propionyl, pivaloyl, and 1-adamantanecarbonyl, 19-21) were prepared with increasing bulk around the thio ester bond. The benzoyl derivatives contained aromatic substituents chosen from a sigma-pi cluster chart so that the esters prepared had a wide range of electronic and solubility properties. In general, compounds with substituents which increased lipid solubility [p-chlorobenzoyl (4), p-trifluoromethylbenzoyl (6), and pivaloyl (20)] had the greatest potency at a dose of 300 mg/kg. Hydrolysis rates, measured at pH 6 and 8, indicated that in vivo breakdown to 3-MPA probably did not account for the observed hypoglycemic activity of the esters. 4, 6, and 20 were less potent than 3-MPA in comparative dose range studies."}
{"id": "PMID:15115", "title": "Relative concentrations of zwitterionic and uncharged species in catecholamines and the effect of N-substituents.", "content": "The relative concentrations of zwitterionic and uncharged species for the series of N-substituted catecholamines (I, R1 = R2 = OH; R = H, Me, Et, i-Pr, t-Bu) are derived from the pKa data published in 1962 by Sinistri and Villa. The concentration ratios, represented by the tautomeric equilibrium constant Kt, show a definite trend and are respectively 1.8, 4.3, 4.7, 4.7, and 7.1. These values suggest that any mechanism of action involving proton transfer, which might transform the zwitterion into the uncharged form, would be most favorable for norepinephrine and least favorable fo the t-Bu derivative.", "contents": "Relative concentrations of zwitterionic and uncharged species in catecholamines and the effect of N-substituents. The relative concentrations of zwitterionic and uncharged species for the series of N-substituted catecholamines (I, R1 = R2 = OH; R = H, Me, Et, i-Pr, t-Bu) are derived from the pKa data published in 1962 by Sinistri and Villa. The concentration ratios, represented by the tautomeric equilibrium constant Kt, show a definite trend and are respectively 1.8, 4.3, 4.7, 4.7, and 7.1. These values suggest that any mechanism of action involving proton transfer, which might transform the zwitterion into the uncharged form, would be most favorable for norepinephrine and least favorable fo the t-Bu derivative."}
{"id": "PMID:15123", "title": "Interviewing skills: a comprehensive approach to teaching and evaluation.", "content": "Evaluation procedures utilizing standardized interviews scored by means of a formal objective rating system which make it possible to measure the interviewing skills of health professional students have been developed in recent years. These procedures have been used in the Child Health Associate Program at the University of Colorado Medical School to evaluate the ability of a group of students to achieve the objectives of a practice-oriented interviewing course. Results from the standardized interviews indicate that students taking the course gathered an average of 76 percent of all available data and used 86 percent of the process skills defined as necessary for positive interview interaction. A previous group of child health associate students who did not take the course gathered an average of 47 percent of all available data and used an average of 62 percent of the necessary process skills.", "contents": "Interviewing skills: a comprehensive approach to teaching and evaluation. Evaluation procedures utilizing standardized interviews scored by means of a formal objective rating system which make it possible to measure the interviewing skills of health professional students have been developed in recent years. These procedures have been used in the Child Health Associate Program at the University of Colorado Medical School to evaluate the ability of a group of students to achieve the objectives of a practice-oriented interviewing course. Results from the standardized interviews indicate that students taking the course gathered an average of 76 percent of all available data and used 86 percent of the process skills defined as necessary for positive interview interaction. A previous group of child health associate students who did not take the course gathered an average of 47 percent of all available data and used an average of 62 percent of the necessary process skills."}
{"id": "PMID:15124", "title": "Evaluation of a child health associate program.", "content": "The staff of the University of Colorado Child Health Associate Program critically reviewed the effectiveness of the program's structure and content during an intensive two-day seminar. The review was conducted through workshops involving participants representing students, graduates, faculty, employers, funding agencies, university administrators, and educational consultants. The agenda for the evaluation included workshops on specific topics such as basic and clinical sciences, psychosocial skills, and proficiency testing. Information obtained provided extremely valuable data which were used to improve the program.", "contents": "Evaluation of a child health associate program. The staff of the University of Colorado Child Health Associate Program critically reviewed the effectiveness of the program's structure and content during an intensive two-day seminar. The review was conducted through workshops involving participants representing students, graduates, faculty, employers, funding agencies, university administrators, and educational consultants. The agenda for the evaluation included workshops on specific topics such as basic and clinical sciences, psychosocial skills, and proficiency testing. Information obtained provided extremely valuable data which were used to improve the program."}
{"id": "PMID:15125", "title": "A protonmotive force as the source of energy for galactoside transport in energy depleted Escherichia coli.", "content": "An artificially produced electrochemical potential difference for protons (portonmotive force) provided the energy for the transport of galactosides in Escherichia coli cells which were depleted of their endogenous energy reserves. The driving force for the entry of protons was provided by either a transmembrane pH gradient or a membrane potential. The pH gradient across the membrane was created by acidifying the external medium. The membrane potential (inside negative) was established by the outward diffusion of potassium (in the presence of valinomycin) or by the inward diffusion of the permeant thiocyanate ion. The magnitude of the electrochemical potential difference for protons agreed well with magnitude of the chemical potential difference of the lactose analog, thiomethylgalactoside. The observations are consistent with the view that the carrier-mediated entry of each galactoside molecule is accompanied by the entry of one proton.", "contents": "A protonmotive force as the source of energy for galactoside transport in energy depleted Escherichia coli. An artificially produced electrochemical potential difference for protons (portonmotive force) provided the energy for the transport of galactosides in Escherichia coli cells which were depleted of their endogenous energy reserves. The driving force for the entry of protons was provided by either a transmembrane pH gradient or a membrane potential. The pH gradient across the membrane was created by acidifying the external medium. The membrane potential (inside negative) was established by the outward diffusion of potassium (in the presence of valinomycin) or by the inward diffusion of the permeant thiocyanate ion. The magnitude of the electrochemical potential difference for protons agreed well with magnitude of the chemical potential difference of the lactose analog, thiomethylgalactoside. The observations are consistent with the view that the carrier-mediated entry of each galactoside molecule is accompanied by the entry of one proton."}
{"id": "PMID:15126", "title": "Studies on the cation permeability of human red cell ghosts. Characterization and biological significance of two membrane sites with high affinities for Ca.", "content": "Net K movements in reconstituted human red cell ghosts and the resealing of ghosts to cations after osmotic hemolysis of red cells have been studied as functions of the free Ca ion concentration. The Ca-dependent specific increase in K permeability was shown to be mediated by a site close to the internal surface of the membrane with an apparent dissociation constant ap pH 7.2 for Ca (K'p1) of 3-5 X 10(-7) M, for Sr of 7 X 10(-6) M. Ba and Mg did not increase the K-permeability of the membrane but inhibited the Ca-mediated permeability changes. K'D1 decreased in a nonlinear fashion when the pH was increased from 6.0 to 8.5. Two different pK' values of this membrane site were found at pH 8.3 and 6.3. The Ca-activated net K efflux into a K-free medium was almost completely inhibited by an increase in intracellular Na from 4 to 70mM. Extracellular K antagonized this Na effect. Changes in the extracellular Na (0.1-140 mM) or K (0.1-6 mM) concentrations had little effect and did not change K'p1. The Ca-stimulated recovery of a low cation permeability in ghost cells appeared to be mediated by a second membrane site which was accessible to divalent cations only during the process of hemolysis in media of low ionic strength. The apparent dissociation constant for Ca at this site (K'p2) varied between 6 X 10(-7) and 4 X 10(-6) M at pH 7.2 Mg, Sr, and Ba could replace Ca functionally. The selectivity sequence was Ca greater than Sr greater than Ba greater than Mg. K'p2 was independent on the pH value in the range between 6.0 and 8.0 Hill coefficients of 2 were observed for the interaction of Ca with both  membrane sites suggesting that more than one Ca ion is bound per site. The Hill cofficients were affected neither by the ion composition nor by the Ph values of the intra-and extracellular media. It is concluded that two different pathways for the permeation of cations across the membrane are controlled by membrane sites with high affinities for Ca: One specific for K, one unspecific with respect to cations. The K-specific \"channel\" has properties similar to the K channel in excitable tissues.", "contents": "Studies on the cation permeability of human red cell ghosts. Characterization and biological significance of two membrane sites with high affinities for Ca. Net K movements in reconstituted human red cell ghosts and the resealing of ghosts to cations after osmotic hemolysis of red cells have been studied as functions of the free Ca ion concentration. The Ca-dependent specific increase in K permeability was shown to be mediated by a site close to the internal surface of the membrane with an apparent dissociation constant ap pH 7.2 for Ca (K'p1) of 3-5 X 10(-7) M, for Sr of 7 X 10(-6) M. Ba and Mg did not increase the K-permeability of the membrane but inhibited the Ca-mediated permeability changes. K'D1 decreased in a nonlinear fashion when the pH was increased from 6.0 to 8.5. Two different pK' values of this membrane site were found at pH 8.3 and 6.3. The Ca-activated net K efflux into a K-free medium was almost completely inhibited by an increase in intracellular Na from 4 to 70mM. Extracellular K antagonized this Na effect. Changes in the extracellular Na (0.1-140 mM) or K (0.1-6 mM) concentrations had little effect and did not change K'p1. The Ca-stimulated recovery of a low cation permeability in ghost cells appeared to be mediated by a second membrane site which was accessible to divalent cations only during the process of hemolysis in media of low ionic strength. The apparent dissociation constant for Ca at this site (K'p2) varied between 6 X 10(-7) and 4 X 10(-6) M at pH 7.2 Mg, Sr, and Ba could replace Ca functionally. The selectivity sequence was Ca greater than Sr greater than Ba greater than Mg. K'p2 was independent on the pH value in the range between 6.0 and 8.0 Hill coefficients of 2 were observed for the interaction of Ca with both  membrane sites suggesting that more than one Ca ion is bound per site. The Hill cofficients were affected neither by the ion composition nor by the Ph values of the intra-and extracellular media. It is concluded that two different pathways for the permeation of cations across the membrane are controlled by membrane sites with high affinities for Ca: One specific for K, one unspecific with respect to cations. The K-specific \"channel\" has properties similar to the K channel in excitable tissues."}
{"id": "PMID:15129", "title": "Enhancement of 5-iododeoxyuridine-induced endogenous C-type virus activation by polycyclic hydrocarbons: apparent lack of parallelism between enhancement and carcinogenicity.", "content": "When mouse MLg cells were treated with 3-methylcholanthrene or 7,12-dimethylbenz[alpha]anthracene in the presence of microsomal enzymes and NADPH after 5-iododeoxyuridine (IUDR) treatment, the induction rate of the endogenous C-type virus was increased fivefold to sixfold in comparison with the culture treated with IUDR only. In this reaction, both the microsomal enzymes and NADPH were indispensable. 7,8-Benzoflavone, an inhibitor of the metabolism of hydrocarbons in hamster embryo cultures, inhibited the reaction. For detecting the enhancing activity, the concentration of IUDR for the pretreatment, the concentration of the test products, and the duration of the treatment with the products were important factors. In screening 30 polycyclic hydrocarbons, we were unable to detect a correlation between the in vivo carcinogenicity in the skin and the enhancing activity in the conditions tested.", "contents": "Enhancement of 5-iododeoxyuridine-induced endogenous C-type virus activation by polycyclic hydrocarbons: apparent lack of parallelism between enhancement and carcinogenicity. When mouse MLg cells were treated with 3-methylcholanthrene or 7,12-dimethylbenz[alpha]anthracene in the presence of microsomal enzymes and NADPH after 5-iododeoxyuridine (IUDR) treatment, the induction rate of the endogenous C-type virus was increased fivefold to sixfold in comparison with the culture treated with IUDR only. In this reaction, both the microsomal enzymes and NADPH were indispensable. 7,8-Benzoflavone, an inhibitor of the metabolism of hydrocarbons in hamster embryo cultures, inhibited the reaction. For detecting the enhancing activity, the concentration of IUDR for the pretreatment, the concentration of the test products, and the duration of the treatment with the products were important factors. In screening 30 polycyclic hydrocarbons, we were unable to detect a correlation between the in vivo carcinogenicity in the skin and the enhancing activity in the conditions tested."}
{"id": "PMID:15130", "title": "Lack of influence of hypophysectomy on estrogen-induced DNA synthesis in Leydig cells of BALB/c mice.", "content": "In mice of strains susceptible to Leydig cell tumor induction, treatment with estrogens induced a \"spurt\" of DNA synthesis within the first few days. This synthetic activity generally subsided, until areas of Leydig cell hyperplasia developed several months later. Autoradiographic and quantitative biochemical studies indicated that in BALB/c mice this initial DNA synthetic activity occurred in the absence of the hypophysis and apparently was the result of effects of estrogen directly on Leydig cells. Although hypophysectomy inhibited sperm maturation, [3H]thymidine incorporation into spermatogonia was reduced only slightly 2 weeks after surgery, as was the induced DNA spurt in the interstitial tissues.", "contents": "Lack of influence of hypophysectomy on estrogen-induced DNA synthesis in Leydig cells of BALB/c mice. In mice of strains susceptible to Leydig cell tumor induction, treatment with estrogens induced a \"spurt\" of DNA synthesis within the first few days. This synthetic activity generally subsided, until areas of Leydig cell hyperplasia developed several months later. Autoradiographic and quantitative biochemical studies indicated that in BALB/c mice this initial DNA synthetic activity occurred in the absence of the hypophysis and apparently was the result of effects of estrogen directly on Leydig cells. Although hypophysectomy inhibited sperm maturation, [3H]thymidine incorporation into spermatogonia was reduced only slightly 2 weeks after surgery, as was the induced DNA spurt in the interstitial tissues."}
{"id": "PMID:15131", "title": "Effect of hyperthermia and environmental acidity on the proteolytic activity in murine ascites tumor cells.", "content": "The influence of hyperthermia and environmental pH on proteolytic activity was studied in murine ascites tumor cells in vitro. PNJ ascites tumor cells were incubated with [125I]cytochrome c at 42.5 or 37 degrees C in a modified Krebs-Ringer buffer adjusted to pH 7.2 or 6.4. Incubation at normal temperature at pH 6.4 and 7.2 or at 42.5 degrees C and pH 7.2 resulted in identical protein digestion. However, hyperthermic incubation at pH 6.4 resulted in a significant increased activity. This was also observed after only 1 hour of hyperthermic incubation followed by subsequent incubation in an acidic environment at normal temperature. The increased proteolytic activity following hyperthermic treatment under acidic conditions may support the hypothesis that increased lysosomal activity is of primary importance in the hyperthermic tumor-cell destruction in vivo.", "contents": "Effect of hyperthermia and environmental acidity on the proteolytic activity in murine ascites tumor cells. The influence of hyperthermia and environmental pH on proteolytic activity was studied in murine ascites tumor cells in vitro. PNJ ascites tumor cells were incubated with [125I]cytochrome c at 42.5 or 37 degrees C in a modified Krebs-Ringer buffer adjusted to pH 7.2 or 6.4. Incubation at normal temperature at pH 6.4 and 7.2 or at 42.5 degrees C and pH 7.2 resulted in identical protein digestion. However, hyperthermic incubation at pH 6.4 resulted in a significant increased activity. This was also observed after only 1 hour of hyperthermic incubation followed by subsequent incubation in an acidic environment at normal temperature. The increased proteolytic activity following hyperthermic treatment under acidic conditions may support the hypothesis that increased lysosomal activity is of primary importance in the hyperthermic tumor-cell destruction in vivo."}
{"id": "PMID:15132", "title": "Nature of the delayed graft-versus-host reactivity of fetal liver cell transplants in mice.", "content": "Experiments were designed to determine which actual differences in the cellular composition between fetal liver and bone marrow account for the distinct types of graft-versus-host (GvH) disease. The assay of reactive lymphocytes (by in vitro mitogenic stimulation) in fetal liver transplants in mice, the purification of hemopoietic stem cells (HSC) of the transplants, and the quantitation of HSC numbers in the grafts traced the basis for the distinctly weak type of GvH disease after fetal liver cell grafts. It was found that transplantation of purified HSC concentrates did not modify the severity of GvH mortality. The moderate character of the delayed GvH disease was shown to depend on the presence of an HSC population in fetal liver with different qualities and not on numerical differences between the HSC in fetal liver and bone marrow. Data collected also demonstrated that when GvH disease occurred in the recipients of transplants of fetal liver, it shared the characteristic histologic features of the bone marrow GvH syndrome. The recovery of mitogen responsiveness of spleen cells may have been delayed in fetal liver allotransplantation as compared to syngeneic grafting. By supportive infusion of lymphoid cells, it was suggested that the immunodeficiency coinciding with GvH disease represented a secondary manifestation of the disease rather than a primary impairment in lymphoid differentiation.", "contents": "Nature of the delayed graft-versus-host reactivity of fetal liver cell transplants in mice. Experiments were designed to determine which actual differences in the cellular composition between fetal liver and bone marrow account for the distinct types of graft-versus-host (GvH) disease. The assay of reactive lymphocytes (by in vitro mitogenic stimulation) in fetal liver transplants in mice, the purification of hemopoietic stem cells (HSC) of the transplants, and the quantitation of HSC numbers in the grafts traced the basis for the distinctly weak type of GvH disease after fetal liver cell grafts. It was found that transplantation of purified HSC concentrates did not modify the severity of GvH mortality. The moderate character of the delayed GvH disease was shown to depend on the presence of an HSC population in fetal liver with different qualities and not on numerical differences between the HSC in fetal liver and bone marrow. Data collected also demonstrated that when GvH disease occurred in the recipients of transplants of fetal liver, it shared the characteristic histologic features of the bone marrow GvH syndrome. The recovery of mitogen responsiveness of spleen cells may have been delayed in fetal liver allotransplantation as compared to syngeneic grafting. By supportive infusion of lymphoid cells, it was suggested that the immunodeficiency coinciding with GvH disease represented a secondary manifestation of the disease rather than a primary impairment in lymphoid differentiation."}
{"id": "PMID:15133", "title": "Characterization of group H streptococcal temperate bacteriophage phi 227.", "content": "phi 227, a temperate phage from a group H streptococcus (Streptococcus sanguis), was propagated vegetatively in group H strain Wicky 4-EryR, and its characteristics were determined. A procedure dependent on multiplicity of infection, incubation time, and treatment of crude lysates with diatomaceous earth was found to optimize phage yield, resulting in titers of 1 X 10(10) to 2 X 10(10) PFU/ml. Without prior treatment with diatomaceous earth, subsequent purification procedures (methanol, ammonium sulfate, polyethylene glycol) gave recoveries of less than 1% of crude lysate titers. Adsorption of phi227 to host cells was relatively unaffected by the medium, but calcium (not substituted by magnesium) was required for formation of infectious centers. The phage receptor was present on purified cell walls, resisted trypsin and heat, and was removed ty hydrochloric acid, trichloracetic acid, and hot formamide: however, formamide-extracted material failed to inactivate phage, and the nature of the receptor is unknown. Single-step growth experiments showed a latent period of 39 min and a burst size of 100 PFU/infectious center; results were unaffected by omission of supplemental Ca2+, by supplementation with Mg2, addition of glucose, or changes of pH between 6.35 and 8.0; but increased temperature (40 to 43 degrees C) shortened the latent period and decreased the burst size. The latent period was prolonged in genetically competent host cells and in chemically defined medium; and in the latter, the burst size was smaller. Phage replication was sensitive to those metabolic inhibitors which inhibited the host streptococcus: these included rifampin, fluorodeoxyuridine, hydroxyurea, dihydrostreptomycin, and 6-P-hydroxyphenylazouracil. The data suggest that phi227 does not code for a rifampin-resistant RNA polymerase. However, in a rifampin-resistant host strain, phage replication and lysogen formation were both decreased suggesting that altered host core polymerase had less affinity for (some) promotors on the phi227 template. In transfection, a Ca2+-dependent stabilization step that was inhibited by Mg2+ was demonstrated; transformation was not affected by either Ca2+ or Mg2+, and the site and nature of the stabilization are unknown. More than one molecule of DNA was required for plaque formation. Biophysical characterization showed a type B phage of buoyant density (CsCl) 1.50, containing five proteins and 54.8% DNA. The duplex linear DNA had a molecular weight (calculated from contour length) of 23.2 X 10(6) and a guanine plus cytosine content (calculated from melting point) of 42.3 mol%. Similar characterizations of streptococcal phages, including biophysical data, have not been previously available.", "contents": "Characterization of group H streptococcal temperate bacteriophage phi 227. phi 227, a temperate phage from a group H streptococcus (Streptococcus sanguis), was propagated vegetatively in group H strain Wicky 4-EryR, and its characteristics were determined. A procedure dependent on multiplicity of infection, incubation time, and treatment of crude lysates with diatomaceous earth was found to optimize phage yield, resulting in titers of 1 X 10(10) to 2 X 10(10) PFU/ml. Without prior treatment with diatomaceous earth, subsequent purification procedures (methanol, ammonium sulfate, polyethylene glycol) gave recoveries of less than 1% of crude lysate titers. Adsorption of phi227 to host cells was relatively unaffected by the medium, but calcium (not substituted by magnesium) was required for formation of infectious centers. The phage receptor was present on purified cell walls, resisted trypsin and heat, and was removed ty hydrochloric acid, trichloracetic acid, and hot formamide: however, formamide-extracted material failed to inactivate phage, and the nature of the receptor is unknown. Single-step growth experiments showed a latent period of 39 min and a burst size of 100 PFU/infectious center; results were unaffected by omission of supplemental Ca2+, by supplementation with Mg2, addition of glucose, or changes of pH between 6.35 and 8.0; but increased temperature (40 to 43 degrees C) shortened the latent period and decreased the burst size. The latent period was prolonged in genetically competent host cells and in chemically defined medium; and in the latter, the burst size was smaller. Phage replication was sensitive to those metabolic inhibitors which inhibited the host streptococcus: these included rifampin, fluorodeoxyuridine, hydroxyurea, dihydrostreptomycin, and 6-P-hydroxyphenylazouracil. The data suggest that phi227 does not code for a rifampin-resistant RNA polymerase. However, in a rifampin-resistant host strain, phage replication and lysogen formation were both decreased suggesting that altered host core polymerase had less affinity for (some) promotors on the phi227 template. In transfection, a Ca2+-dependent stabilization step that was inhibited by Mg2+ was demonstrated; transformation was not affected by either Ca2+ or Mg2+, and the site and nature of the stabilization are unknown. More than one molecule of DNA was required for plaque formation. Biophysical characterization showed a type B phage of buoyant density (CsCl) 1.50, containing five proteins and 54.8% DNA. The duplex linear DNA had a molecular weight (calculated from contour length) of 23.2 X 10(6) and a guanine plus cytosine content (calculated from melting point) of 42.3 mol%. Similar characterizations of streptococcal phages, including biophysical data, have not been previously available."}
{"id": "PMID:15134", "title": "Characterization of components released by alkali disruption of simian virus 40.", "content": "Treatment of simian virus 40 (SV40) particles at pH 9.8 in the presence of 1 mM dithiothreitol for 5 min at 37 degrees C disrupted the virions into a 60S DNA-protein complex and DNA-free 7S protein particles. The DNA-protein complex contained approximately equal amounts of DNA and protein, and appeared by electron microscopy to be relaxed circular structures with an average of 21 beads joined by short, thin bridges. The major protein components in the complex were host cell histones, but SV40-specific proteins VP3 and VP2 were also present. The 7S protein particles were almost exclusively VP1 and, in negatively stained samples, resembled the capsomer structures of intact virions.", "contents": "Characterization of components released by alkali disruption of simian virus 40. Treatment of simian virus 40 (SV40) particles at pH 9.8 in the presence of 1 mM dithiothreitol for 5 min at 37 degrees C disrupted the virions into a 60S DNA-protein complex and DNA-free 7S protein particles. The DNA-protein complex contained approximately equal amounts of DNA and protein, and appeared by electron microscopy to be relaxed circular structures with an average of 21 beads joined by short, thin bridges. The major protein components in the complex were host cell histones, but SV40-specific proteins VP3 and VP2 were also present. The 7S protein particles were almost exclusively VP1 and, in negatively stained samples, resembled the capsomer structures of intact virions."}
{"id": "PMID:15135", "title": "Temperature-sensitive defect of vesicular stomatitis virus in complementation group II.", "content": "The prototype member of the complementation group II temperature-sensitive (ts) mutants of vesicular stomatitis virus, ts II 052, has been investigated. In ts II 052-infected HeLa cells at the restrictive temperature (39.5 degrees C), reduced viral RNA synthesis was observed by comparison with infections conducted at the permissive temperature (30 degrees C). It was found that for an infection conducted at 39.5 degrees C, no 38S RNA or intracytoplasmic nucleocapsids were present. For nucleocapsids isolated from ts II 052 purified virions or from ts II 052-infected cells at 30 degrees C, the RNA was sensitive to pancreatic RNase after an exposure at 39.5 degrees C in contrast to the resistance observed for wild-type virus. The nucleocapsid stability of wild-type virus when heated to 63 degrees C or submitted to varying pH was not found in nucleocapsids extracted from ts II 052 purified virions. The data suggest that for ts II 052 there is an altered relationship between the viral 38S RNA and the nucleocapsid protein(s) by comparison with wild-type virus. Such results argue for the complementation group II gene product being N protein, so that the ts defect in ts II 052 represents an altered N protein.", "contents": "Temperature-sensitive defect of vesicular stomatitis virus in complementation group II. The prototype member of the complementation group II temperature-sensitive (ts) mutants of vesicular stomatitis virus, ts II 052, has been investigated. In ts II 052-infected HeLa cells at the restrictive temperature (39.5 degrees C), reduced viral RNA synthesis was observed by comparison with infections conducted at the permissive temperature (30 degrees C). It was found that for an infection conducted at 39.5 degrees C, no 38S RNA or intracytoplasmic nucleocapsids were present. For nucleocapsids isolated from ts II 052 purified virions or from ts II 052-infected cells at 30 degrees C, the RNA was sensitive to pancreatic RNase after an exposure at 39.5 degrees C in contrast to the resistance observed for wild-type virus. The nucleocapsid stability of wild-type virus when heated to 63 degrees C or submitted to varying pH was not found in nucleocapsids extracted from ts II 052 purified virions. The data suggest that for ts II 052 there is an altered relationship between the viral 38S RNA and the nucleocapsid protein(s) by comparison with wild-type virus. Such results argue for the complementation group II gene product being N protein, so that the ts defect in ts II 052 represents an altered N protein."}
{"id": "PMID:15136", "title": "Receptor interaction between eastern equine encephalitis virus and chicken embryo fibroblasts.", "content": "The attachment of eastern equine encephalitis virus to chicken embryo fibroblasts was studied at 0 degrees C. The binding specifically responsible for initiating infection was studied in the initial experiments by employing plaque-forming ability as the measured response. Results from these initial studies were closely paralleled in studies of binding of radiolabeled virus under the same conditions. Binding that had occurred at the pH optimum, pH 6.5, could be reversed only at higher pH. The observed pH dependence of virus attachment suggested the interaction of at least two ionizable species in the initial binding of virus to cell, and that one to three attachments must occur between virus and cell prior to infection.", "contents": "Receptor interaction between eastern equine encephalitis virus and chicken embryo fibroblasts. The attachment of eastern equine encephalitis virus to chicken embryo fibroblasts was studied at 0 degrees C. The binding specifically responsible for initiating infection was studied in the initial experiments by employing plaque-forming ability as the measured response. Results from these initial studies were closely paralleled in studies of binding of radiolabeled virus under the same conditions. Binding that had occurred at the pH optimum, pH 6.5, could be reversed only at higher pH. The observed pH dependence of virus attachment suggested the interaction of at least two ionizable species in the initial binding of virus to cell, and that one to three attachments must occur between virus and cell prior to infection."}
{"id": "PMID:15137", "title": "Priapism: evolution of management in 48 patients in a 22-year series.", "content": "The choice of an effective method to treat priapism is challenging because precise causes in the majority of patients have not been well defined. A review of 48 patients treated during a 22-year period shows evolution of a regimen of management that has yielded a high percentage of success. Idiopathic priapism and sickle cell disease accounted for 81 per cent of the subjects. An evaluation should include a medication history, a search for specific diseases, as well as a thorough physical examination to detect possible etiologic factors. The explanation for the frequent association of fever deserves further investigation. Initial therapy consisting of aspiration and irrigation, and intermittent pneumatic cuff compression should be undertaken for a trial period of 12 to 36 hours, repeating the aspiration 2 or 3 times if necessary. The failure of priapism to resolve after such treatment is an indication for a shunt operation. Patients with known etiology should be treated specifically for the primary disease and usually more conservatively for priapism. Resolution occurred in all patients and approximately 50 per cent regained sexual potency.", "contents": "Priapism: evolution of management in 48 patients in a 22-year series. The choice of an effective method to treat priapism is challenging because precise causes in the majority of patients have not been well defined. A review of 48 patients treated during a 22-year period shows evolution of a regimen of management that has yielded a high percentage of success. Idiopathic priapism and sickle cell disease accounted for 81 per cent of the subjects. An evaluation should include a medication history, a search for specific diseases, as well as a thorough physical examination to detect possible etiologic factors. The explanation for the frequent association of fever deserves further investigation. Initial therapy consisting of aspiration and irrigation, and intermittent pneumatic cuff compression should be undertaken for a trial period of 12 to 36 hours, repeating the aspiration 2 or 3 times if necessary. The failure of priapism to resolve after such treatment is an indication for a shunt operation. Patients with known etiology should be treated specifically for the primary disease and usually more conservatively for priapism. Resolution occurred in all patients and approximately 50 per cent regained sexual potency."}
{"id": "PMID:15139", "title": "Venographic localization of the non-palpable undescended testis in children.", "content": "In cases of bilateral non-palpable undescended testes in which human chorionic gonadotropin stimulation has shown the presence of testicular tissue and in cases of unilateral non-palpable undescended testes selective transfemoral gonadal venography with a modified Seldinger technique has been used for the preoperative localization of the non-palpable testis. since the undescended testis may be located anywhere along the course of its embryologic descent, that is from the level of the renal fossa to its exit from the inguinal canal, preoperative localization will aid in the surgical management. Gonadal venography has proved to be accurate and safe, and has aided in the determination of the extent of surgical exploration in 9 children with 12 non-palpable undescended testes (6 right and 6 left).", "contents": "Venographic localization of the non-palpable undescended testis in children. In cases of bilateral non-palpable undescended testes in which human chorionic gonadotropin stimulation has shown the presence of testicular tissue and in cases of unilateral non-palpable undescended testes selective transfemoral gonadal venography with a modified Seldinger technique has been used for the preoperative localization of the non-palpable testis. since the undescended testis may be located anywhere along the course of its embryologic descent, that is from the level of the renal fossa to its exit from the inguinal canal, preoperative localization will aid in the surgical management. Gonadal venography has proved to be accurate and safe, and has aided in the determination of the extent of surgical exploration in 9 children with 12 non-palpable undescended testes (6 right and 6 left)."}
{"id": "PMID:15141", "title": "The effects of glucose infusion on myocardial performance during acute hypoxia.", "content": "The effects of hypoxia with or without glucose infusion on the cardiac contractility, blood pressure, electrocardiogram, blood electrolytes (sodium and potassium), glucose, pH, Po2, and Pco2 in anesthetized dogs were studied. Hypoxia was induced by ventilating the dogs with reduced oxygen (10%) in the inspired air. Hypoxia produced a decrease in the cardiac contractility and blood pressure, and an increase in the heart rate and central venous pressure. It produced a decrease in the blood pH, Po2, and Pco2, and an increase in the blood glucose and potassium. Glucose infusion during hypoxia delayed the rate of decrease in the contractility and blood pressure significantly. The time for decrease in the contracility to 45 to 50% was increased by 67%. Glucose infusion prevented the loss of potassium from the cell. Glucose infusion however, was unable to correct acidosis. These results indicate that glucose infusion during hypoxia might prevent or delay the deterioration of myocardial function.", "contents": "The effects of glucose infusion on myocardial performance during acute hypoxia. The effects of hypoxia with or without glucose infusion on the cardiac contractility, blood pressure, electrocardiogram, blood electrolytes (sodium and potassium), glucose, pH, Po2, and Pco2 in anesthetized dogs were studied. Hypoxia was induced by ventilating the dogs with reduced oxygen (10%) in the inspired air. Hypoxia produced a decrease in the cardiac contractility and blood pressure, and an increase in the heart rate and central venous pressure. It produced a decrease in the blood pH, Po2, and Pco2, and an increase in the blood glucose and potassium. Glucose infusion during hypoxia delayed the rate of decrease in the contractility and blood pressure significantly. The time for decrease in the contracility to 45 to 50% was increased by 67%. Glucose infusion prevented the loss of potassium from the cell. Glucose infusion however, was unable to correct acidosis. These results indicate that glucose infusion during hypoxia might prevent or delay the deterioration of myocardial function."}
{"id": "PMID:15142", "title": "Effects of beta-adrenergic blocking agents on the blood pressure, plasma renin activity and hemodynamics of hypertensive patients.", "content": "Changes in blood pressure, plasma renin activity, and hemodynamic components were studied in 23 patients with essential hypertension treated with oral pindolol or propranolol. These beta-adrenergic blocking agents effectively lowered the blood pressure in the majority of the patients. Although plasma renin activity was not significantly changed, the higher was the pretreatment level, the more it tended to be decreased. Systemic vascular resistence was significantly decreased, while changes in cardiac index and circulating blood volume were variable. Pindolol showed less effect in reducing the heart rate than propranolol. The antihypertensive effect of these drugs had no correlation with the change in plasma renin activity or in any one of hemodynamic components.", "contents": "Effects of beta-adrenergic blocking agents on the blood pressure, plasma renin activity and hemodynamics of hypertensive patients. Changes in blood pressure, plasma renin activity, and hemodynamic components were studied in 23 patients with essential hypertension treated with oral pindolol or propranolol. These beta-adrenergic blocking agents effectively lowered the blood pressure in the majority of the patients. Although plasma renin activity was not significantly changed, the higher was the pretreatment level, the more it tended to be decreased. Systemic vascular resistence was significantly decreased, while changes in cardiac index and circulating blood volume were variable. Pindolol showed less effect in reducing the heart rate than propranolol. The antihypertensive effect of these drugs had no correlation with the change in plasma renin activity or in any one of hemodynamic components."}
{"id": "PMID:15147", "title": "[Metabolism of tetrachloroethylene in guinea pigs (author's transl)].", "content": "Tetrachloroethylene oxide was chemically prepared from tetrachloroethylene, and the metabolites of the oxide in guinea pigs were analyzed by gaschromatography and Fujiwara reaction. The results obtained are as follows: 1) Trichloroacetic acid appeared in gaschromatogram after injection of tetrachloroethylene oxide, but trichloroethanol did not. 2) The metabolites analyzed by Fujiwara reaction after injection of tetrachloroethylene oxide were composed of large proportion of trichloroacetic acid and small proportion of trichloroethanol. 3) The ratio of trichloroacetic acid to trichloroethanol in the urine in case of tetrachloroethylene oxide was relatively similar to that of tetrachloroethylene. 4) The effects of pH (2.0 and 10.0) and temperature (4 degrees C and 37 degrees C) on the urinary metabolites suggest that the substance equivalent to trichloroethanol by Fujiwara reaction in metabolites may not be a real one. 5) Toxicity of tetrachloroethylene oxide seems to be much higher as compared with that of tetrachloroethylene in consideration of the maximum allowable dose in guinea pigs. 6) It is supposed from our experiments that tetrachloroethylene oxide is an intermediary metabolite of tetrachloroethylene.", "contents": "[Metabolism of tetrachloroethylene in guinea pigs (author's transl)]. Tetrachloroethylene oxide was chemically prepared from tetrachloroethylene, and the metabolites of the oxide in guinea pigs were analyzed by gaschromatography and Fujiwara reaction. The results obtained are as follows: 1) Trichloroacetic acid appeared in gaschromatogram after injection of tetrachloroethylene oxide, but trichloroethanol did not. 2) The metabolites analyzed by Fujiwara reaction after injection of tetrachloroethylene oxide were composed of large proportion of trichloroacetic acid and small proportion of trichloroethanol. 3) The ratio of trichloroacetic acid to trichloroethanol in the urine in case of tetrachloroethylene oxide was relatively similar to that of tetrachloroethylene. 4) The effects of pH (2.0 and 10.0) and temperature (4 degrees C and 37 degrees C) on the urinary metabolites suggest that the substance equivalent to trichloroethanol by Fujiwara reaction in metabolites may not be a real one. 5) Toxicity of tetrachloroethylene oxide seems to be much higher as compared with that of tetrachloroethylene in consideration of the maximum allowable dose in guinea pigs. 6) It is supposed from our experiments that tetrachloroethylene oxide is an intermediary metabolite of tetrachloroethylene."}
{"id": "PMID:15148", "title": "Serum gamma-glutamyl transpeptidase as a diagnostic aid in the periodic health examination.", "content": "Serum gamma-glutamyl transpeptidase is one of the enzymes in diagnosis of liver diseases, since a new colorimetric method was devised by Orlowski, M. et al. Forty mU/ml of serum gamma-glutamyl transpeptidase activity is said to be the upper limit at clinical level. When this value is set up as a screening level in the periodic health examination, about 35% of the subjects including daily drinkers can be evaluated as abnormal. In the present study, the upper limits of serum gamma-glutamyl transpeptidase activity were 102 mU/ml for 147 normal subjects including daily drinkers and 49 mU/ml in 70 non-drinkers selected from the subjects. Therefore, we propose that the standards for screening the abnormal from the normal in the periodic health examination should be 50 mU/ml for non-drinkers and 100 mU/ml for drinkers.", "contents": "Serum gamma-glutamyl transpeptidase as a diagnostic aid in the periodic health examination. Serum gamma-glutamyl transpeptidase is one of the enzymes in diagnosis of liver diseases, since a new colorimetric method was devised by Orlowski, M. et al. Forty mU/ml of serum gamma-glutamyl transpeptidase activity is said to be the upper limit at clinical level. When this value is set up as a screening level in the periodic health examination, about 35% of the subjects including daily drinkers can be evaluated as abnormal. In the present study, the upper limits of serum gamma-glutamyl transpeptidase activity were 102 mU/ml for 147 normal subjects including daily drinkers and 49 mU/ml in 70 non-drinkers selected from the subjects. Therefore, we propose that the standards for screening the abnormal from the normal in the periodic health examination should be 50 mU/ml for non-drinkers and 100 mU/ml for drinkers."}
{"id": "PMID:15149", "title": "[Studies on the adsorption removal of ammonia gas. 1) Adsorption of ammonia gas on several kinds of activated carbons (author's transl)].", "content": "The present study was designed to secure some fundamental informations on the adsorption removal of ammonia gas by the static method. In order to find out the suitable activated carbons for the adsorption removal of ammonia gas, amounts of ammonia gas adsorbed on twelve kinds of activated carbons were measured at 30 degrees C and up to 70,000 ppm of ammonia gas. The relations between the amounts of ammonia gas adsorbed on the activated carbons and the physical properties of them were discussed through the results of specific surface area, pore volume, mean pore radius, scanning electron micrograph, pH, and amount of base. The results were as follows: 1) Among the twelve kinds of activated carbons, the activated carbons No. 2, No. 3, and No. 6 adsorbed larger amount of ammonia gas than the others. 2) Adsorption of ammonia gas on the activated carbons seemed to be mainly physical as judged from the values of heat of adsorption. 3) The adsorption capacity of the used activated carbons can be recovered to the original capacity by some treatment. 4) The period to reach adsorption equilibrium was about 5 minutes. 5) It may be concluded that adsorption of ammonia gas on the activated carbons was decided mainly by the surface properties  (pH and amount of base) of the activated carbons rather than their porous structures.", "contents": "[Studies on the adsorption removal of ammonia gas. 1) Adsorption of ammonia gas on several kinds of activated carbons (author's transl)]. The present study was designed to secure some fundamental informations on the adsorption removal of ammonia gas by the static method. In order to find out the suitable activated carbons for the adsorption removal of ammonia gas, amounts of ammonia gas adsorbed on twelve kinds of activated carbons were measured at 30 degrees C and up to 70,000 ppm of ammonia gas. The relations between the amounts of ammonia gas adsorbed on the activated carbons and the physical properties of them were discussed through the results of specific surface area, pore volume, mean pore radius, scanning electron micrograph, pH, and amount of base. The results were as follows: 1) Among the twelve kinds of activated carbons, the activated carbons No. 2, No. 3, and No. 6 adsorbed larger amount of ammonia gas than the others. 2) Adsorption of ammonia gas on the activated carbons seemed to be mainly physical as judged from the values of heat of adsorption. 3) The adsorption capacity of the used activated carbons can be recovered to the original capacity by some treatment. 4) The period to reach adsorption equilibrium was about 5 minutes. 5) It may be concluded that adsorption of ammonia gas on the activated carbons was decided mainly by the surface properties  (pH and amount of base) of the activated carbons rather than their porous structures."}
{"id": "PMID:15153", "title": "Effects of bufetolol and propranolol on active and passive membrane properties of dog papillary muscle.", "content": "Effects of bufetolol and propranolol, adrenergic beta-receptor blocking and anti-arrhythmic drugs, on active and passive membrane properties of the dog papillary muscle were investigated with microelectrode and sucrose-gap methods. Bufetolol (10(-5) to 10(-4) g/ml) and propranolol (10(-6) g/ml) significantly decreased the maximum rate of rise of the action potential. The maximum responsive frequency to driving stimulus was decreased in the presence of bufetolol (3 X 10(-5) g/ml) and propranolol (10(-5 g/ml), whereas the effective refractory period was not affected. The critical threshold potential was shifted to more positive potential in the presence of the drugs. The passive membrane property, the space constant (lambda), the time constant (tau) and the current-voltage relations of the muscle membrane were not significantly altered by the drugs. It is concluded that bufetolol and propranolol suppress the excitability of the muscle membrane and this action may be ascribed to the decrease in the sodium conductance (gNa) and to the rise of gNa onset potential without alteration in the passive membrane property.", "contents": "Effects of bufetolol and propranolol on active and passive membrane properties of dog papillary muscle. Effects of bufetolol and propranolol, adrenergic beta-receptor blocking and anti-arrhythmic drugs, on active and passive membrane properties of the dog papillary muscle were investigated with microelectrode and sucrose-gap methods. Bufetolol (10(-5) to 10(-4) g/ml) and propranolol (10(-6) g/ml) significantly decreased the maximum rate of rise of the action potential. The maximum responsive frequency to driving stimulus was decreased in the presence of bufetolol (3 X 10(-5) g/ml) and propranolol (10(-5 g/ml), whereas the effective refractory period was not affected. The critical threshold potential was shifted to more positive potential in the presence of the drugs. The passive membrane property, the space constant (lambda), the time constant (tau) and the current-voltage relations of the muscle membrane were not significantly altered by the drugs. It is concluded that bufetolol and propranolol suppress the excitability of the muscle membrane and this action may be ascribed to the decrease in the sodium conductance (gNa) and to the rise of gNa onset potential without alteration in the passive membrane property."}
{"id": "PMID:15154", "title": "Effects of L-glutamine on acetylsalycylic acid induced gastric lesions and acid back diffusion in dogs.", "content": "Effects of L-glutamine on acetylsalicylic acid (ASA)-induced gastric mucosal lesions were studied in mongrel dogs. It was confirmed that when oral ASA at 1.0 or 2.0 g per dog is given in two divided doses, there is severe and consistent dose-dependent mucosal damage in the glandular portion of the stomach in fasted dogs. However, when L-glutamine 2.0 or 4.0 g per dog in two divided doses is given concomitantly with ASA 2.0 g per dog orally, the gastric irritation is significantly inhibited. Instillation of 20 mM of ASA in 100 mM HCl solution into the Heidenhain pouch of Beagle dogs produced a significant loss of H+ from the pouch and a gain of Na+ in the lumen compared with ASA-free controls. When L-glutamine (100 mM) was given concomitantly with ASA (20 mM) into the pouch, changes of electrolyte fluxes in response to ASA alone were significantly suppressed. However, 50 mM of L-glutamine had no appreciable effect on acid back diffusion caused by ASA 20 mM. The amino acid itself had little effect on the ionic movement in the pouch. Gross bleeding from the pouch treated with ASA was never observed with the concomitant dosing of ASA and L-glutamine 50 or 100 mM.", "contents": "Effects of L-glutamine on acetylsalycylic acid induced gastric lesions and acid back diffusion in dogs. Effects of L-glutamine on acetylsalicylic acid (ASA)-induced gastric mucosal lesions were studied in mongrel dogs. It was confirmed that when oral ASA at 1.0 or 2.0 g per dog is given in two divided doses, there is severe and consistent dose-dependent mucosal damage in the glandular portion of the stomach in fasted dogs. However, when L-glutamine 2.0 or 4.0 g per dog in two divided doses is given concomitantly with ASA 2.0 g per dog orally, the gastric irritation is significantly inhibited. Instillation of 20 mM of ASA in 100 mM HCl solution into the Heidenhain pouch of Beagle dogs produced a significant loss of H+ from the pouch and a gain of Na+ in the lumen compared with ASA-free controls. When L-glutamine (100 mM) was given concomitantly with ASA (20 mM) into the pouch, changes of electrolyte fluxes in response to ASA alone were significantly suppressed. However, 50 mM of L-glutamine had no appreciable effect on acid back diffusion caused by ASA 20 mM. The amino acid itself had little effect on the ionic movement in the pouch. Gross bleeding from the pouch treated with ASA was never observed with the concomitant dosing of ASA and L-glutamine 50 or 100 mM."}
{"id": "PMID:15157", "title": "Complement-independent nephrotoxic nephritis in the guinea pig.", "content": "Immunologic mechanisms of proteinuria were investigated in guinea pigs (GP) injected with sheep antiserum (NTS) to GP glomerular basement membrane (GBM). Linear deposition of sheep gamma 1 and gamma 2 IgG led to a prompt but transient (36 hr) increase in albumin excretion from control values of 0.026 +/- 0.013 mg/hr to maximal values of 26+/-12.1 mg/rh at six hours without detectable histologic or electron microscopic changes except for decreased staining for glomerular polyanion and epithelial cell foot process fusion. GBM permeability to anionic ferritin was not increased during proteinuria. Anti-GBM antibody deposits did not fix GP C3 or C4 in vivo or in vitro. NTS-induced proteinuria was the same in guinea pigs that were normal, greater than 95% depleted of C3 through C9, genetically deficient in C4, and depleted of circulating polymorphonuclear leukocytes (PMN). Prior administration of antihistamines, steroids, azathioprine, colchicine, indomethacin, heparin, aprotinin (Trasylol), and niridazole also failed to reduced proteinuria. Initial proteinuria subsided by 36 hr, did not recur despite linear deposition of GP gemma 1 and gemma 2 after day seven, and antibody to GMB-bound sheep globlin. In the GP nephrotoxic nephritis model, anti-GBM antibody deposits apparently mediate increased permeability to albumin by a currently undefined mechanism which is independent of complement, PMN, and other know mediators of inflammation.", "contents": "Complement-independent nephrotoxic nephritis in the guinea pig. Immunologic mechanisms of proteinuria were investigated in guinea pigs (GP) injected with sheep antiserum (NTS) to GP glomerular basement membrane (GBM). Linear deposition of sheep gamma 1 and gamma 2 IgG led to a prompt but transient (36 hr) increase in albumin excretion from control values of 0.026 +/- 0.013 mg/hr to maximal values of 26+/-12.1 mg/rh at six hours without detectable histologic or electron microscopic changes except for decreased staining for glomerular polyanion and epithelial cell foot process fusion. GBM permeability to anionic ferritin was not increased during proteinuria. Anti-GBM antibody deposits did not fix GP C3 or C4 in vivo or in vitro. NTS-induced proteinuria was the same in guinea pigs that were normal, greater than 95% depleted of C3 through C9, genetically deficient in C4, and depleted of circulating polymorphonuclear leukocytes (PMN). Prior administration of antihistamines, steroids, azathioprine, colchicine, indomethacin, heparin, aprotinin (Trasylol), and niridazole also failed to reduced proteinuria. Initial proteinuria subsided by 36 hr, did not recur despite linear deposition of GP gemma 1 and gemma 2 after day seven, and antibody to GMB-bound sheep globlin. In the GP nephrotoxic nephritis model, anti-GBM antibody deposits apparently mediate increased permeability to albumin by a currently undefined mechanism which is independent of complement, PMN, and other know mediators of inflammation."}
{"id": "PMID:15159", "title": "[Chloroquine keratopathy as an example of drug-induced phospholipidosis (contribution to the pathogenesis of cornea verticillata) (author's transl)].", "content": "Chronic treatment with certain drugs induces morphological alterations in the eye which are histologically and electron microscopically identical with those found in hereditary lipidoses (cornea verticillata, e.g. in M. Fabry). Hereditary storage diseases are the consequence of enzyme defects, the mechanism underlying the side effect of certain drugs, however, is quite different. \"Amphiphilic\" drugs from completely different pharmacological groups, like chloroquine, amiodarone, chlorpromazine form complexes with cellular phospholipids which cannot be metabolised by lysosomal phospholipases. Thus in all tissues with high phospholipid content or turnover typical intracellular deposites with lamellary or crystalloid structure may occur (myelin figures). Such deposites were observed in different parts of the eye and are known e.g. from the cornea as \"cornea verticillata\".", "contents": "[Chloroquine keratopathy as an example of drug-induced phospholipidosis (contribution to the pathogenesis of cornea verticillata) (author's transl)]. Chronic treatment with certain drugs induces morphological alterations in the eye which are histologically and electron microscopically identical with those found in hereditary lipidoses (cornea verticillata, e.g. in M. Fabry). Hereditary storage diseases are the consequence of enzyme defects, the mechanism underlying the side effect of certain drugs, however, is quite different. \"Amphiphilic\" drugs from completely different pharmacological groups, like chloroquine, amiodarone, chlorpromazine form complexes with cellular phospholipids which cannot be metabolised by lysosomal phospholipases. Thus in all tissues with high phospholipid content or turnover typical intracellular deposites with lamellary or crystalloid structure may occur (myelin figures). Such deposites were observed in different parts of the eye and are known e.g. from the cornea as \"cornea verticillata\"."}
{"id": "PMID:15163", "title": "Carbon tetrachloride-induced changes in mixed function oxidases and microsomal cytochromes in the rat lung.", "content": "The effects of a single exposure, by gastric intubation or inhalation, to carbon tetrachloride (CCL4) on rat lungs were assessed. By 1 to 7 days, focal areas of alveolar collapse, septal edema, and modification of type II pneumonocytes were observed. By 24 hours after exposure to the toxin, there were no identifiable changes in surfactant levels or distribution. Microsomes obtained from the lungs and prepared for analysis revealed marked decreases in cytochrome P-450 content and P-450-related N-demethylation of dimethylaniline. Only a transient reduction of cytochrome b5 occurred, with a rebound exceeding control values during the period of pulmonary healing. Whether the lung acted as an excretory route (following intubation) or as an absorption path (after inhalation) made little difference. Carbon tetrachloride had no effect on in vitro microsome composition and function unless supplemented with a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) generating system. Under these circumstances, there was a reduction in both cytochromes b5 and P-450. Our data indicate that a considerable chemical modification of the pulmonary tissues had taken place, with no accompanying easily recognized changes in cellular structure. Furthermore, evidence for the in vitro destruction of pulmonary microsomal cytochromes P-450 and b5, unrelated to peroxidation, is indicated by these findings.", "contents": "Carbon tetrachloride-induced changes in mixed function oxidases and microsomal cytochromes in the rat lung. The effects of a single exposure, by gastric intubation or inhalation, to carbon tetrachloride (CCL4) on rat lungs were assessed. By 1 to 7 days, focal areas of alveolar collapse, septal edema, and modification of type II pneumonocytes were observed. By 24 hours after exposure to the toxin, there were no identifiable changes in surfactant levels or distribution. Microsomes obtained from the lungs and prepared for analysis revealed marked decreases in cytochrome P-450 content and P-450-related N-demethylation of dimethylaniline. Only a transient reduction of cytochrome b5 occurred, with a rebound exceeding control values during the period of pulmonary healing. Whether the lung acted as an excretory route (following intubation) or as an absorption path (after inhalation) made little difference. Carbon tetrachloride had no effect on in vitro microsome composition and function unless supplemented with a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) generating system. Under these circumstances, there was a reduction in both cytochromes b5 and P-450. Our data indicate that a considerable chemical modification of the pulmonary tissues had taken place, with no accompanying easily recognized changes in cellular structure. Furthermore, evidence for the in vitro destruction of pulmonary microsomal cytochromes P-450 and b5, unrelated to peroxidation, is indicated by these findings."}
{"id": "PMID:15164", "title": "Acid hydrolases. Assay of activity and latency in the varied mixed cell populations of canine gastric mucosa.", "content": "The specific enzymic properties, membrane or particle binding capacities, and the total activities of certain acid hydrolases, including cathepsin D, acid phosphatase, arylsulfatase, and five acid glycosidases have been compared in normal canine antral and fundic mucosae and in liver. The two major regions of the gastric mucosa, whose cell populations are comparable in type but have very distinct functions, also differ in many properties of their lysosomal enzymes. These differences necessitate several major modification in their method of assay. Using optimal conditions, the activities of most of these enzymes were found to differ: levels in the antrum, in spite of its high water and mucin-glycoprotein content, were significantly greater, suggesting that the high lysosomal hydrolytic activity may be associated with the rapid autophagic processes of normal turnover of its surface epithelial and mucous neck cells. Lysosomal membrane stability or latency is also greater in the antrum; this may account, in part at least, for antral resistance to erosions brought about by stress.", "contents": "Acid hydrolases. Assay of activity and latency in the varied mixed cell populations of canine gastric mucosa. The specific enzymic properties, membrane or particle binding capacities, and the total activities of certain acid hydrolases, including cathepsin D, acid phosphatase, arylsulfatase, and five acid glycosidases have been compared in normal canine antral and fundic mucosae and in liver. The two major regions of the gastric mucosa, whose cell populations are comparable in type but have very distinct functions, also differ in many properties of their lysosomal enzymes. These differences necessitate several major modification in their method of assay. Using optimal conditions, the activities of most of these enzymes were found to differ: levels in the antrum, in spite of its high water and mucin-glycoprotein content, were significantly greater, suggesting that the high lysosomal hydrolytic activity may be associated with the rapid autophagic processes of normal turnover of its surface epithelial and mucous neck cells. Lysosomal membrane stability or latency is also greater in the antrum; this may account, in part at least, for antral resistance to erosions brought about by stress."}
{"id": "PMID:15165", "title": "An evaluation of the immune state in leprosy.", "content": "An evaluation of the immune state in leprosy was done by the application of a system of graft-versus-host reaction. Peripheral blood lymphocytes obtained from patients with different forms of leprosy and from normal healthy individuals were injected intravenously into the irradiated mice. The rate of blast transformation of the donor cells was measured by the radio-active thymidine uptake. The number of cells labelled with tritiated-thymidine was much higher in the normal individuals and patients with tuberculoid leprosy than in the patients with lepromatous leprosy with the borderline group placed in between the two. However, following successful treatment with DDS, an increased responsiveness and active DNA synthesis could be observed in the previously less responsive lepromatous lymphocytes.", "contents": "An evaluation of the immune state in leprosy. An evaluation of the immune state in leprosy was done by the application of a system of graft-versus-host reaction. Peripheral blood lymphocytes obtained from patients with different forms of leprosy and from normal healthy individuals were injected intravenously into the irradiated mice. The rate of blast transformation of the donor cells was measured by the radio-active thymidine uptake. The number of cells labelled with tritiated-thymidine was much higher in the normal individuals and patients with tuberculoid leprosy than in the patients with lepromatous leprosy with the borderline group placed in between the two. However, following successful treatment with DDS, an increased responsiveness and active DNA synthesis could be observed in the previously less responsive lepromatous lymphocytes."}
{"id": "PMID:15161", "title": "[Intestinal autoflora of the test subjects in a 6-month biological engineering experiment].", "content": "During a 6-month bioengineering experiment the intestinal microflora of four test subjects was examined. Changes in the composition of different groups of intestinal microflora (bifidobacteria, lactic-acid bacteria, sporogenous anaerobes, proteus, etc) were found. In spite of the unstable pattern of the intestinal microflora and its tendency for simplification, the total number of microorganisms in 1 g of feces remained relatively unchanged in all the test subjects.", "contents": "[Intestinal autoflora of the test subjects in a 6-month biological engineering experiment]. During a 6-month bioengineering experiment the intestinal microflora of four test subjects was examined. Changes in the composition of different groups of intestinal microflora (bifidobacteria, lactic-acid bacteria, sporogenous anaerobes, proteus, etc) were found. In spite of the unstable pattern of the intestinal microflora and its tendency for simplification, the total number of microorganisms in 1 g of feces remained relatively unchanged in all the test subjects."}
{"id": "PMID:15162", "title": "[Sensitivity of animals to central nervous system stimulants in hypokinesia].", "content": "The experiments were carried out on 1150 non-inbred white male rats weighing 200+/-50 g. The animals were housed in small cages for 1, 5, 10, 15, 30, 45 and 60 days. Control rats remained normally active. The experimental and control animals were given a typical diet. On the above days the rats were injected intraperitoneally with central nervous stimulants--caffeine, phenamine and strychnine. Changes in the animal sensitivity to the stimulants were measured with respect to the alterating of LD16, LD50 and LD54 in test animals as compared with the controls and in regards to the emergence and duration of behavioural reactions: adynamics (caffeine), stereotype behavior (phenamine) and convulsions (strychnine). The greatest changes in the animal sensitivity were noted in response to phenamine. A significant increase in the sensitivity to caffeine was found on the 5, 15 and 45th experimental days and to strychnine only on the 5 and 45th days. Convulsions in response to strychnine were recorded in experimental animals earlier than in the controls and their duration was dependent on the doses injected. Adynamics in response to caffeine developed in experimental rats later than in the controls (on the 15th day) and its duration changed cyclically. Stereotype behavior in response to phenamine showed cyclic pattern and its duration in experimental rats was shorter than in the controls.", "contents": "[Sensitivity of animals to central nervous system stimulants in hypokinesia]. The experiments were carried out on 1150 non-inbred white male rats weighing 200+/-50 g. The animals were housed in small cages for 1, 5, 10, 15, 30, 45 and 60 days. Control rats remained normally active. The experimental and control animals were given a typical diet. On the above days the rats were injected intraperitoneally with central nervous stimulants--caffeine, phenamine and strychnine. Changes in the animal sensitivity to the stimulants were measured with respect to the alterating of LD16, LD50 and LD54 in test animals as compared with the controls and in regards to the emergence and duration of behavioural reactions: adynamics (caffeine), stereotype behavior (phenamine) and convulsions (strychnine). The greatest changes in the animal sensitivity were noted in response to phenamine. A significant increase in the sensitivity to caffeine was found on the 5, 15 and 45th experimental days and to strychnine only on the 5 and 45th days. Convulsions in response to strychnine were recorded in experimental animals earlier than in the controls and their duration was dependent on the doses injected. Adynamics in response to caffeine developed in experimental rats later than in the controls (on the 15th day) and its duration changed cyclically. Stereotype behavior in response to phenamine showed cyclic pattern and its duration in experimental rats was shorter than in the controls."}
{"id": "PMID:15169", "title": "Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain II. Tyrosine hydroxylase in the telencephalon.", "content": "Extensive plexuses of TH-positive nerve terminals were found in many parts of the telencephalon, mainly confined to the subcortical and limbic cortical structures. Of special interest were the distinct networks of varying densities in the amygdaloid cortex, the entorhinal cortex, the prepiriform cortex, the anterior cingulate cortex and the (pre-)frontal cortex. Their distribution is identical with the patterns observed in recent studies on cortical dopamine nerve terminals using certain modifications of the Falck-Hillarp technique. The extremely dense TH innervations patterns of the caudate nucleus, nucleus accumbens, tuberculum olfactorium and the less dense basket-like innervation of the lateral septal nuclei could also be demonstrated. TH-positive cell bodies in a periglomerular position could be observed in the olfactory bulb. A few TH-positive cell bodies were observed in the area around the anterior commissure and in the cingulate cortex. In one area, the hippocampal formation, TH-positive dotlike structures were located in the position of the mossy fibres. In all probability they do not belong to monoamine neurons but may contain a cross-reacting protein. In general, the distribution and density of TH-positive terminals agrees well with extensive regional, biochemical studies on TH activity performed by other groups. Minor discrepancies are discussed. As stated in a parallel study on the distribution of TH in the mes- and diencephalon these findings indicate that TH activity is closely related to the amount of enzyme protein. The TH enzyme levels seem to be much higher in the DA than in the NA nerve terminals of the forebrain which would explain the preferential demonstration of DA terminals in the forebrain using TH antiserum and the high and low TH enzyme activity in DA and NA rich regions, respectively.", "contents": "Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain II. Tyrosine hydroxylase in the telencephalon. Extensive plexuses of TH-positive nerve terminals were found in many parts of the telencephalon, mainly confined to the subcortical and limbic cortical structures. Of special interest were the distinct networks of varying densities in the amygdaloid cortex, the entorhinal cortex, the prepiriform cortex, the anterior cingulate cortex and the (pre-)frontal cortex. Their distribution is identical with the patterns observed in recent studies on cortical dopamine nerve terminals using certain modifications of the Falck-Hillarp technique. The extremely dense TH innervations patterns of the caudate nucleus, nucleus accumbens, tuberculum olfactorium and the less dense basket-like innervation of the lateral septal nuclei could also be demonstrated. TH-positive cell bodies in a periglomerular position could be observed in the olfactory bulb. A few TH-positive cell bodies were observed in the area around the anterior commissure and in the cingulate cortex. In one area, the hippocampal formation, TH-positive dotlike structures were located in the position of the mossy fibres. In all probability they do not belong to monoamine neurons but may contain a cross-reacting protein. In general, the distribution and density of TH-positive terminals agrees well with extensive regional, biochemical studies on TH activity performed by other groups. Minor discrepancies are discussed. As stated in a parallel study on the distribution of TH in the mes- and diencephalon these findings indicate that TH activity is closely related to the amount of enzyme protein. The TH enzyme levels seem to be much higher in the DA than in the NA nerve terminals of the forebrain which would explain the preferential demonstration of DA terminals in the forebrain using TH antiserum and the high and low TH enzyme activity in DA and NA rich regions, respectively."}
{"id": "PMID:15170", "title": "pH-dependency in diffusion of some weakly acidic drugs, warfarin, sulfaethidole, and barbital, into organic phases.", "content": "The diffusion of three weakly acidic drugs (warfarin, sulfaethidole, and barbital) in cyclohexane-buffer and n-octanol-buffer systems was studied by two different methods; shaking and model cell type of experimentation. At low pH values the drugs moved generally more readily into the organic phases than at higher pH. Moreover, when the shaking method was used the drugs moved readily to the n-octanol phase even at higher pH levels. Lecithin improved the diffusion at low more than at high pH levels. Thus, the results varied according to the organic phase selected and the method used.  Poor correlation was found between some results of this study and previously reported results of in situ absorption from the rat gastrointestinal tract of the same drugs. The results do not support the assumption that phospholipids may have a role in the absorption of ionized moieties.", "contents": "pH-dependency in diffusion of some weakly acidic drugs, warfarin, sulfaethidole, and barbital, into organic phases. The diffusion of three weakly acidic drugs (warfarin, sulfaethidole, and barbital) in cyclohexane-buffer and n-octanol-buffer systems was studied by two different methods; shaking and model cell type of experimentation. At low pH values the drugs moved generally more readily into the organic phases than at higher pH. Moreover, when the shaking method was used the drugs moved readily to the n-octanol phase even at higher pH levels. Lecithin improved the diffusion at low more than at high pH levels. Thus, the results varied according to the organic phase selected and the method used.  Poor correlation was found between some results of this study and previously reported results of in situ absorption from the rat gastrointestinal tract of the same drugs. The results do not support the assumption that phospholipids may have a role in the absorption of ionized moieties."}
{"id": "PMID:15177", "title": "Involvement of cytochrome b5 in the oxidative desaturation of linoleic acid to gamma-linolenic acid in rat liver microsomes.", "content": "The effects of antibodies against microsomal electron-transport components on the in vitro activity of delta6-desaturation of linoleic acid to gamma-linolenic acid have been studied in intact microsomal membranes of rat liver. Reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) (0.87 mM) served as electron donors, and effectively prompted the delta6-desaturase activities with yields of about 1.1 to 1.3 nmol per mg of protein in 10 min. Of the two antibodies studied under the same in vitro conditions, i.e., rabbit antisera preparations against rat liver microsomal hydrophilic parts of cytochrome b5 and NADPH-cytochrome c reductase, only the antibody against cytochrome b5 demonstrated a marked ability to inhibit the delta6-desaturase activity. This evidence supports a participation of cytochrome b5 in the delta6-desaturation of linoleic acid and suggests a pathway analogous to the delta9-desaturation of stearyl-CoA.", "contents": "Involvement of cytochrome b5 in the oxidative desaturation of linoleic acid to gamma-linolenic acid in rat liver microsomes. The effects of antibodies against microsomal electron-transport components on the in vitro activity of delta6-desaturation of linoleic acid to gamma-linolenic acid have been studied in intact microsomal membranes of rat liver. Reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) (0.87 mM) served as electron donors, and effectively prompted the delta6-desaturase activities with yields of about 1.1 to 1.3 nmol per mg of protein in 10 min. Of the two antibodies studied under the same in vitro conditions, i.e., rabbit antisera preparations against rat liver microsomal hydrophilic parts of cytochrome b5 and NADPH-cytochrome c reductase, only the antibody against cytochrome b5 demonstrated a marked ability to inhibit the delta6-desaturase activity. This evidence supports a participation of cytochrome b5 in the delta6-desaturation of linoleic acid and suggests a pathway analogous to the delta9-desaturation of stearyl-CoA."}
{"id": "PMID:15178", "title": "Glycerokinase in human adipose tissue.", "content": "The presence of glycerokinase has been demonstrated in human omental and subcutaneous adipose tissue. The enzyme reaction showed a linear time course for 5 min at 30 C and pH optima at pH 7.6 and 9.0. Saturation of the enzyme was observed at 1.8 mM adenosine triphosphate (ATP) and the double reciprocal plot of activity vs. ATP concentration was nonlinear giving two apparent Km values of 0.094 and 0.518 mM. The apparent Km for glycerol, 0.112 mM, was obtained from a linear double reciprocal plot, and the enzyme was saturated at about 0.4 mM glycerol. The activity of glycerokinase in human adipose tissue excised under general anaesthesia was low and was unrelated to adipose cell size or the degree of obesity of the subject from whom the fat was obtained.", "contents": "Glycerokinase in human adipose tissue. The presence of glycerokinase has been demonstrated in human omental and subcutaneous adipose tissue. The enzyme reaction showed a linear time course for 5 min at 30 C and pH optima at pH 7.6 and 9.0. Saturation of the enzyme was observed at 1.8 mM adenosine triphosphate (ATP) and the double reciprocal plot of activity vs. ATP concentration was nonlinear giving two apparent Km values of 0.094 and 0.518 mM. The apparent Km for glycerol, 0.112 mM, was obtained from a linear double reciprocal plot, and the enzyme was saturated at about 0.4 mM glycerol. The activity of glycerokinase in human adipose tissue excised under general anaesthesia was low and was unrelated to adipose cell size or the degree of obesity of the subject from whom the fat was obtained."}
{"id": "PMID:15181", "title": "Some respiratory and metabolic effects of exercise in moderately obese men.", "content": "The effects of varying levels of exercise on oxygen uptake, CO2 production, blood pressure, arterial blood gasses, and arterial concentrations of glucose, insulin, and growth hormone were examined in ten normal weight and ten moderately overweight young men. At comparable external work loads with a bicycle ergometer, the lean men required less oxygen than the obese men. When oxygen uptakes were matched during exercise on a treadmill, the lean men were walking on a steeper grade or at a higher rate than the obese men. The efficiency of exercise as assessed by the relation between oxygen uptake and work did not differ between the two groups. Blood pressure rose more in the obese during exercise than in the lean. The fall in lactate and rise in bicarbonate was of greater magnitude during cycle ergometry than during treadmill exercise. Obese and lean men, however, showed similar changes. With each level of exercise, there was a fall in arterial insulin levels, but the concentrations in the blood of overweight men always remained significantly above that of the normal men. Growth hormones tended to be higher in the normal weight men, but the differences were usually not significant, and there was no significant rise with exercise in either group until the highest levels of work were achieved. Glucose concentrations tended to be higher in the obese men, but fell to constant levels in both groups during exercise. Blood pressure rose to a greater extent in the overweight men during exercise.", "contents": "Some respiratory and metabolic effects of exercise in moderately obese men. The effects of varying levels of exercise on oxygen uptake, CO2 production, blood pressure, arterial blood gasses, and arterial concentrations of glucose, insulin, and growth hormone were examined in ten normal weight and ten moderately overweight young men. At comparable external work loads with a bicycle ergometer, the lean men required less oxygen than the obese men. When oxygen uptakes were matched during exercise on a treadmill, the lean men were walking on a steeper grade or at a higher rate than the obese men. The efficiency of exercise as assessed by the relation between oxygen uptake and work did not differ between the two groups. Blood pressure rose more in the obese during exercise than in the lean. The fall in lactate and rise in bicarbonate was of greater magnitude during cycle ergometry than during treadmill exercise. Obese and lean men, however, showed similar changes. With each level of exercise, there was a fall in arterial insulin levels, but the concentrations in the blood of overweight men always remained significantly above that of the normal men. Growth hormones tended to be higher in the normal weight men, but the differences were usually not significant, and there was no significant rise with exercise in either group until the highest levels of work were achieved. Glucose concentrations tended to be higher in the obese men, but fell to constant levels in both groups during exercise. Blood pressure rose to a greater extent in the overweight men during exercise."}
{"id": "PMID:15198", "title": "Paradoxical reaction to a new minor tranquilizer.", "content": "This case report demonstrates that paradoxical reactions to the benzodiazepine class of minor tranquilizer can occur, and that lorazepam, a new derivative, is not free from this effect. It also lends support to the hypothesis that such reactions may be precipitated by a frustrating stimulus, and this has clinical relevance in that such precipitants may well be similar to those situations producing anxiety for which the drug had been prescribed.", "contents": "Paradoxical reaction to a new minor tranquilizer. This case report demonstrates that paradoxical reactions to the benzodiazepine class of minor tranquilizer can occur, and that lorazepam, a new derivative, is not free from this effect. It also lends support to the hypothesis that such reactions may be precipitated by a frustrating stimulus, and this has clinical relevance in that such precipitants may well be similar to those situations producing anxiety for which the drug had been prescribed."}
{"id": "PMID:15207", "title": "Enzyme transformations.", "content": "The paper briefly discusses the current theories on the processes underlying the transformation of the catalytic activity of a number of enzymes. The phenomenon of transformation, which is induced by mild chemical effects acting on a protein, is of interest both from the point of view of the investigation of its molecular mechanisms and from the point of view of the study of several pathological states under which this phenomenon is observed. Gorkin's own data are presented.", "contents": "Enzyme transformations. The paper briefly discusses the current theories on the processes underlying the transformation of the catalytic activity of a number of enzymes. The phenomenon of transformation, which is induced by mild chemical effects acting on a protein, is of interest both from the point of view of the investigation of its molecular mechanisms and from the point of view of the study of several pathological states under which this phenomenon is observed. Gorkin's own data are presented."}
{"id": "PMID:15209", "title": "Interaction of transfer RNA with 50S ribosomal subunits of Escherichia coli in absence of templates.", "content": "The equilibrium constant of a complex of tRNA with the 50S ribosomal subunit was measured in the absence of a template. It was shown that the stability of the complex increases with an increase in the concentration of Mg2+, it decreases with an increase in the concentration of univalent ions, and does not depend on the pH of the medium in the range of 7.0-8.2. Removal of the 3'-terminal nucleoside of tRNA weakens the association approximately 40-fold; the subsequent successive splitting off of another three nucleotides has little effect on the association constant. In 90% 2H2O the stability of the complex increases approximately four-fold, which points to the large contribution of the hydrogen bonds to the free energy of the interaction. The tetranucleotide TphiCG competes slightly with tRNA for sites on the 50S subparticles; this means that the TphiC segment of tRNA does not play an important role in the formation of the complex under investigation.", "contents": "Interaction of transfer RNA with 50S ribosomal subunits of Escherichia coli in absence of templates. The equilibrium constant of a complex of tRNA with the 50S ribosomal subunit was measured in the absence of a template. It was shown that the stability of the complex increases with an increase in the concentration of Mg2+, it decreases with an increase in the concentration of univalent ions, and does not depend on the pH of the medium in the range of 7.0-8.2. Removal of the 3'-terminal nucleoside of tRNA weakens the association approximately 40-fold; the subsequent successive splitting off of another three nucleotides has little effect on the association constant. In 90% 2H2O the stability of the complex increases approximately four-fold, which points to the large contribution of the hydrogen bonds to the free energy of the interaction. The tetranucleotide TphiCG competes slightly with tRNA for sites on the 50S subparticles; this means that the TphiC segment of tRNA does not play an important role in the formation of the complex under investigation."}
{"id": "PMID:15208", "title": "Presence of a proteinase in polyribosomes of rat liver.", "content": "The presence of a proteinase in the composition of the ribosomal proteins of rat liver is demonstrated. The enzyme possesses optimal activity in the zone of pH 7.0-7.2. Soybean trypsin inhibitor and 1-chloro-4-phenyl-3-tosylamido-2-butanone inhibit the enzyme by 50-60%.", "contents": "Presence of a proteinase in polyribosomes of rat liver. The presence of a proteinase in the composition of the ribosomal proteins of rat liver is demonstrated. The enzyme possesses optimal activity in the zone of pH 7.0-7.2. Soybean trypsin inhibitor and 1-chloro-4-phenyl-3-tosylamido-2-butanone inhibit the enzyme by 50-60%."}
{"id": "PMID:15211", "title": "Ribonuclease and deoxyribonuclease activity of exonuclease A5.", "content": "A comparative study was made of the specificity and some properties of the RNase and DNase activities of exonuclease A5. The results obtained indicate that RNA and denatured DNA are hydrolyzed in the same active center of the enzyme and, consequently, exonuclease A5 is an enzyme which is not specific for the sugar of nucleic acids. The data reported are important when exonuclease A5 is used as a specific reagent in investigations of nucleic acids.", "contents": "Ribonuclease and deoxyribonuclease activity of exonuclease A5. A comparative study was made of the specificity and some properties of the RNase and DNase activities of exonuclease A5. The results obtained indicate that RNA and denatured DNA are hydrolyzed in the same active center of the enzyme and, consequently, exonuclease A5 is an enzyme which is not specific for the sugar of nucleic acids. The data reported are important when exonuclease A5 is used as a specific reagent in investigations of nucleic acids."}
{"id": "PMID:15215", "title": "The influence of pH on the effects of 2,4-D (2,4-dichlorophenoxyacetic acid, Na salt) on Saccharomyces cerevisiae and Salmonella typhimurium.", "content": "The genetic effects of 2,4-D (2,4-dichlorophenoxyacetic acid, Na salt) have been investigated in cells of the yeast Saccharomyces cerevisiae and of the bacterium Salmonella typhimurium in experiments in vitro and in vivo. Experiments in vitro showed that the killing of both yeast and bacteria is dependent on the pH in the treatment solution of 2,4-D. A dose-dependent increase of the frequency of mitotic gene conversion and mitotic recombination in yeast was observed at pH 4.50 and 4.30. In experiments in vitro with two strains of Salmonella no significant increase of the number of revertants to prototrophy was obtained. The positive correlation between survival of cells and dissociation of 2,4-D in the pH region 2.8-5.0 indicates that the cells are unable to take up dissociated 2,4-D. Therefore the survival is high at a high pH when most 2,4-D is in dissociated form, and the survival is low at a relatively low pH when more of the 2,4-D is in its undissociated form. No genetic effects were induced by oral administration of tolerable doses of 2,4-D in host-mediated assays using mice as hosts and yeast or Salmonella as indicator cells.", "contents": "The influence of pH on the effects of 2,4-D (2,4-dichlorophenoxyacetic acid, Na salt) on Saccharomyces cerevisiae and Salmonella typhimurium. The genetic effects of 2,4-D (2,4-dichlorophenoxyacetic acid, Na salt) have been investigated in cells of the yeast Saccharomyces cerevisiae and of the bacterium Salmonella typhimurium in experiments in vitro and in vivo. Experiments in vitro showed that the killing of both yeast and bacteria is dependent on the pH in the treatment solution of 2,4-D. A dose-dependent increase of the frequency of mitotic gene conversion and mitotic recombination in yeast was observed at pH 4.50 and 4.30. In experiments in vitro with two strains of Salmonella no significant increase of the number of revertants to prototrophy was obtained. The positive correlation between survival of cells and dissociation of 2,4-D in the pH region 2.8-5.0 indicates that the cells are unable to take up dissociated 2,4-D. Therefore the survival is high at a high pH when most 2,4-D is in dissociated form, and the survival is low at a relatively low pH when more of the 2,4-D is in its undissociated form. No genetic effects were induced by oral administration of tolerable doses of 2,4-D in host-mediated assays using mice as hosts and yeast or Salmonella as indicator cells."}
{"id": "PMID:15210", "title": "Physicochemical properties of Sendai virus RNA. II. Effect of ionic strength on thermostability of RNA.", "content": "The dependence of the melting point (Tm) and width of the melting range (deltaTm) on the ionic strength and pH of the medium was investigated for the double-stranded RNA formed through self-hybridization during the isolation of RNA from Sendai virus. It was shown that Tm is a linear function of the logarithm of the sodium ion concentration in the range of concentrations from 10(-1) to 10(-4) M, with a slope of 11.5 degrees toward the abscissa for each order of magnitude. The width of the melting range increased slightly with a decrease in the ionic strength. A change in the pH of the solutions from 5 to 8 had almost no effect on the melting point or the width of the melting range. The degree of purification of the preparations of RNA and the presence of EDTA in the solutions affected the form of the dependence of the mp on the logarithm of the sodium ion concentration very strongly, especially in the region of low ionic strengths.", "contents": "Physicochemical properties of Sendai virus RNA. II. Effect of ionic strength on thermostability of RNA. The dependence of the melting point (Tm) and width of the melting range (deltaTm) on the ionic strength and pH of the medium was investigated for the double-stranded RNA formed through self-hybridization during the isolation of RNA from Sendai virus. It was shown that Tm is a linear function of the logarithm of the sodium ion concentration in the range of concentrations from 10(-1) to 10(-4) M, with a slope of 11.5 degrees toward the abscissa for each order of magnitude. The width of the melting range increased slightly with a decrease in the ionic strength. A change in the pH of the solutions from 5 to 8 had almost no effect on the melting point or the width of the melting range. The degree of purification of the preparations of RNA and the presence of EDTA in the solutions affected the form of the dependence of the mp on the logarithm of the sodium ion concentration very strongly, especially in the region of low ionic strengths."}
{"id": "PMID:15216", "title": "Induction of DNA single-strand breaks in barley by sodium azide applied at pH 3.", "content": "Sodium azide (1 to 50 mM), adjusted to pH 3 and applied for 2 h to presoaked barley seeds, induced a dose-dependent frequency of single-strand breaks in DNA of non-germinating embryos. This was demonstrated by sedimentation analyses of isolated DNA samples in alkaline sucrose gradients and in neutral sucrose gradients with 80% formamide. The doses applied also inhibited dose dependently the root length, seed germination and partially the seedling height. Only the sub-lethal doses (10 and 12.5 mM) induced a low frequency of chromatid breaks and translocations in the root tip metaphases. The sedimentation rate (in alkaline sucrose gradients) of calf thymus DNA treated with sodium azide at pH 3, was similar to that of the control DNA treated with buffer (pH 3) alone.", "contents": "Induction of DNA single-strand breaks in barley by sodium azide applied at pH 3. Sodium azide (1 to 50 mM), adjusted to pH 3 and applied for 2 h to presoaked barley seeds, induced a dose-dependent frequency of single-strand breaks in DNA of non-germinating embryos. This was demonstrated by sedimentation analyses of isolated DNA samples in alkaline sucrose gradients and in neutral sucrose gradients with 80% formamide. The doses applied also inhibited dose dependently the root length, seed germination and partially the seedling height. Only the sub-lethal doses (10 and 12.5 mM) induced a low frequency of chromatid breaks and translocations in the root tip metaphases. The sedimentation rate (in alkaline sucrose gradients) of calf thymus DNA treated with sodium azide at pH 3, was similar to that of the control DNA treated with buffer (pH 3) alone."}
{"id": "PMID:15212", "title": "Acceptor activity of tRNAPhe from yeasts under special conditions of aminoacylation.", "content": "The reaction of aminoacylation of tRNAPhe from yeasts and the erroneous acylation of total tRNA from E. coli by yeast phenylalanyl-tRNA synthetase under special conditions was studied. It was shown that the decrease in the degree of acylation of tRNAPhe and the increase in the degree of erroneous acylation of the total tRNA from E. coli are associated with the influence of these conditions on the structure of tRNA, and not on the structure or specificity of the enzyme. It was found that under special conditions of acylation, tRNAPhe exists in two conformations: acylatable and nonacylatable. The ability for complete acylation is restored after the transfer of tRNAPhe under classical conditions of acylation. The results are discussed from the standpoint of possible mechanisms of the recognition of tRNA by aminoacyl-tRNA synthetases.", "contents": "Acceptor activity of tRNAPhe from yeasts under special conditions of aminoacylation. The reaction of aminoacylation of tRNAPhe from yeasts and the erroneous acylation of total tRNA from E. coli by yeast phenylalanyl-tRNA synthetase under special conditions was studied. It was shown that the decrease in the degree of acylation of tRNAPhe and the increase in the degree of erroneous acylation of the total tRNA from E. coli are associated with the influence of these conditions on the structure of tRNA, and not on the structure or specificity of the enzyme. It was found that under special conditions of acylation, tRNAPhe exists in two conformations: acylatable and nonacylatable. The ability for complete acylation is restored after the transfer of tRNAPhe under classical conditions of acylation. The results are discussed from the standpoint of possible mechanisms of the recognition of tRNA by aminoacyl-tRNA synthetases."}
{"id": "PMID:15214", "title": "Thermodynamic parameters of helix-random coil transitions in polypeptide chains. IV. Random copolymers of L-alanine with L-glutamic acid.", "content": "pH-Induced helix-random coil transitions in random copolymers of Ala with Glu have been investigated in order to determine the effect of Ala on the stability of the helical state of polyglutamic acid. The free energies for the transfer of one uncharged Glu residue from a random coil to a helix (deltaGo) have been determined from potentiometric titration curves by the method of Zimm and Rice. It has been shown that the introduction of Ala hampers the transfer of a Glu residue from a random coil to a helix (reduces -deltaGo), although Ala itself is a helix-forming residue, i.e., its free energy decreases during helix formation. This has suggested that its introduction weakens the helix-stabilizing interactions between the uncharged Glu residues (apparently hydrogen bonds). The evaluation of the intrinsic helix-random coil equilibrium constant s for uncharged Glu residues with consideration of this situation yields a value which is smaller than the value of s for (Glu)n and in good agreement with the theoretical values.", "contents": "Thermodynamic parameters of helix-random coil transitions in polypeptide chains. IV. Random copolymers of L-alanine with L-glutamic acid. pH-Induced helix-random coil transitions in random copolymers of Ala with Glu have been investigated in order to determine the effect of Ala on the stability of the helical state of polyglutamic acid. The free energies for the transfer of one uncharged Glu residue from a random coil to a helix (deltaGo) have been determined from potentiometric titration curves by the method of Zimm and Rice. It has been shown that the introduction of Ala hampers the transfer of a Glu residue from a random coil to a helix (reduces -deltaGo), although Ala itself is a helix-forming residue, i.e., its free energy decreases during helix formation. This has suggested that its introduction weakens the helix-stabilizing interactions between the uncharged Glu residues (apparently hydrogen bonds). The evaluation of the intrinsic helix-random coil equilibrium constant s for uncharged Glu residues with consideration of this situation yields a value which is smaller than the value of s for (Glu)n and in good agreement with the theoretical values."}
{"id": "PMID:15219", "title": "Use of amylum derivatives for isolation of amylolytic enzymes.", "content": "In a leading article literature is reviewed concerning isolation of amylolytic enzymes by adsorption on differently modified starches, resp. on other adsorbents. DEAE amylum, DEAHP amylum and DEAE-Sephadex A 25 were found to be most suitable adsorbents. The other adsorbents examined did not reach claimed parameters.", "contents": "Use of amylum derivatives for isolation of amylolytic enzymes. In a leading article literature is reviewed concerning isolation of amylolytic enzymes by adsorption on differently modified starches, resp. on other adsorbents. DEAE amylum, DEAHP amylum and DEAE-Sephadex A 25 were found to be most suitable adsorbents. The other adsorbents examined did not reach claimed parameters."}
{"id": "PMID:15213", "title": "Labilization of the phosphoester linkage in enzyme-inhibitor complexes of aspartate aminotransferase.", "content": "Individual enzyme-inhibitor complexes with characteristic absorption spectra have been obtained as a result of the reaction of the apoenzyme of aspartate aminotransferase with Nalpha-(5'-phosphopyridoxyl)-L-glutamic acid, Nalpha-(5'-phosphopyridoxyl)-D-glutamic acid, and Nalpha-(5'-phosphopyridoxyl)-L-pyroglutamic acid. The stability of the enzyme-inhibitor complexes has been investigated under various conditions, viz., reactivation by the coenzyme, denaturation by urea, variations in the pH. It has been shown that the complexes formed by the last two inhibitors are reactivated by pyridoxal-5'-phosphate and that the inhibitor can be released under mild conditions. The enzyme-inhibitor complex formed by Nalpha-(5'-phosphopyridoxyl)-L-glutamic acid, on the other hand, was not reactivated by the coenzyme. Pyridoxylglutamic acid has been isolate in attempts to release the inhibitor. The dephosphorylation of the inhibitor has been associated both with the hydrolysis of a phosphate bond involving the enzyme and with the phosphorylation of aspartate aminotransferase. A 32P peptide containing 13 amino acids has been isolated from the tryptic hydrolysate of the enzyme-inhibitor complex (formed by a 32P inhibitor). The data obtained have been interpreted on the basis of an assumption that the phosphate group of the coenzyme has an active role in the enzymatic transamination reaction.", "contents": "Labilization of the phosphoester linkage in enzyme-inhibitor complexes of aspartate aminotransferase. Individual enzyme-inhibitor complexes with characteristic absorption spectra have been obtained as a result of the reaction of the apoenzyme of aspartate aminotransferase with Nalpha-(5'-phosphopyridoxyl)-L-glutamic acid, Nalpha-(5'-phosphopyridoxyl)-D-glutamic acid, and Nalpha-(5'-phosphopyridoxyl)-L-pyroglutamic acid. The stability of the enzyme-inhibitor complexes has been investigated under various conditions, viz., reactivation by the coenzyme, denaturation by urea, variations in the pH. It has been shown that the complexes formed by the last two inhibitors are reactivated by pyridoxal-5'-phosphate and that the inhibitor can be released under mild conditions. The enzyme-inhibitor complex formed by Nalpha-(5'-phosphopyridoxyl)-L-glutamic acid, on the other hand, was not reactivated by the coenzyme. Pyridoxylglutamic acid has been isolate in attempts to release the inhibitor. The dephosphorylation of the inhibitor has been associated both with the hydrolysis of a phosphate bond involving the enzyme and with the phosphorylation of aspartate aminotransferase. A 32P peptide containing 13 amino acids has been isolated from the tryptic hydrolysate of the enzyme-inhibitor complex (formed by a 32P inhibitor). The data obtained have been interpreted on the basis of an assumption that the phosphate group of the coenzyme has an active role in the enzymatic transamination reaction."}
{"id": "PMID:15220", "title": "Isolation of amylolytic system of Aspergillus oryzae by sorption on DEAHP amylum.", "content": "Conditions of effective sorption of amylolytic enzyme from a solution or from fermentative liquid on DEAHP amylum were studied. Isolating action is in a direct dependence on the relation between activity and amount of DEAHP amylum, the curve of this dependence was illustrated. The enzyme can be released by elution or adsorbate can be used in a pulverised from. In the conclusion of the work laboratory isolation technique is described.", "contents": "Isolation of amylolytic system of Aspergillus oryzae by sorption on DEAHP amylum. Conditions of effective sorption of amylolytic enzyme from a solution or from fermentative liquid on DEAHP amylum were studied. Isolating action is in a direct dependence on the relation between activity and amount of DEAHP amylum, the curve of this dependence was illustrated. The enzyme can be released by elution or adsorbate can be used in a pulverised from. In the conclusion of the work laboratory isolation technique is described."}
{"id": "PMID:15232", "title": "[Fauna and ecology of bloodsucking mosquitoes of Evenkia].", "content": "This paper presents data on the specific composition, number, hatching sites, seasonal and daily activity of mosquitoes attacking man and reindeer and the influence of weather factors on the attacking activity of mosquitoes in Central Siberia. 23 species of 3 genera are reported from Central Siberia as follows: Anopheles maculipennis, Culiseta alaskaensis, Aedes beklemishevi, A. cantans, A. caspius dorsalis, A. cataphylla, A. communis, A. cyprius, A. diantaeus, A. excrucians, A. fitchii, A. flavescens, A. hexodontus, A. impiger, A. intrudens, A. leucomelas, A. nigripes, A. pionips, A. pullatus, A. punctor, A. rempeli, A. stricticus, A. cinereus.", "contents": "[Fauna and ecology of bloodsucking mosquitoes of Evenkia]. This paper presents data on the specific composition, number, hatching sites, seasonal and daily activity of mosquitoes attacking man and reindeer and the influence of weather factors on the attacking activity of mosquitoes in Central Siberia. 23 species of 3 genera are reported from Central Siberia as follows: Anopheles maculipennis, Culiseta alaskaensis, Aedes beklemishevi, A. cantans, A. caspius dorsalis, A. cataphylla, A. communis, A. cyprius, A. diantaeus, A. excrucians, A. fitchii, A. flavescens, A. hexodontus, A. impiger, A. intrudens, A. leucomelas, A. nigripes, A. pionips, A. pullatus, A. punctor, A. rempeli, A. stricticus, A. cinereus."}
{"id": "PMID:15242", "title": "[Nature of the enzymes participating in the transformation of proinsulin into insulin].", "content": "A study was made of the enzymes of the islands of Langerhans which could participate in the transformation of proinsulin into insulin. The homogenate of the islands of Langerhans of rat and man catalized the hyppuril-L-arginine splitting at pH 5.4-5.8 and 6.8-7.2 which was completely blocked with N-ethyl maleimide. The enzyme of the islands with the optimum action pH of 5.4-5.8 was similar to the enzyme of the exocrine tissue and was possibly a catheptic carboxypeptidase. The second enzyme of the islands differing from the exocrine carboxypeptidase could apparently participate in the insulin formation from the intermediate forms of proinsulin. In the formation of these proinsulin fomrs the participation of the enzyme of the endopeptidase character with a more acid optimum of the action pH is supposed.", "contents": "[Nature of the enzymes participating in the transformation of proinsulin into insulin]. A study was made of the enzymes of the islands of Langerhans which could participate in the transformation of proinsulin into insulin. The homogenate of the islands of Langerhans of rat and man catalized the hyppuril-L-arginine splitting at pH 5.4-5.8 and 6.8-7.2 which was completely blocked with N-ethyl maleimide. The enzyme of the islands with the optimum action pH of 5.4-5.8 was similar to the enzyme of the exocrine tissue and was possibly a catheptic carboxypeptidase. The second enzyme of the islands differing from the exocrine carboxypeptidase could apparently participate in the insulin formation from the intermediate forms of proinsulin. In the formation of these proinsulin fomrs the participation of the enzyme of the endopeptidase character with a more acid optimum of the action pH is supposed."}
{"id": "PMID:15243", "title": "[Laparoscopic diagnosis of cryptorchism].", "content": "On the basis of observations of 28 patients suffering from cryptorchism in which laparoscopy was conducted for the purpose of diagnosis the authors came to the conclusion on the expediency of using this method in the practice of endocrinologist's work.", "contents": "[Laparoscopic diagnosis of cryptorchism]. On the basis of observations of 28 patients suffering from cryptorchism in which laparoscopy was conducted for the purpose of diagnosis the authors came to the conclusion on the expediency of using this method in the practice of endocrinologist's work."}
{"id": "PMID:15244", "title": "[Change in the activity of tyrosine aminotransferase in the tissues of rabbits with various levels of corticosteroids in the body].", "content": "Experiments were conducted on rabbits. As revealed, hypocoriticism was accompanied by a reduction of the tyrosineaminotranspherase in the liver, muscles and blood plasma; the enzyme activity was unchanged in the brain and the spleen. An increase of the corticosteroid level in the organism after the administration of hydrocortisone to the intact and adrenalectomized animals led to increase of the enzyme activity in the tissues under study; the effect of hydrocortisone action depended on the initial hormonal background in the organism and the duration of the hormone administration. A single ACTH administration to the intact rabbits was accompanied by increase in the enzyme activity in the liver and the spleen, whereas to the adrenalectomized animals--in the brain, muscles and the blood plasma. A repeated administration of both hormones decreased the enzyme activity in the brain and the liver.", "contents": "[Change in the activity of tyrosine aminotransferase in the tissues of rabbits with various levels of corticosteroids in the body]. Experiments were conducted on rabbits. As revealed, hypocoriticism was accompanied by a reduction of the tyrosineaminotranspherase in the liver, muscles and blood plasma; the enzyme activity was unchanged in the brain and the spleen. An increase of the corticosteroid level in the organism after the administration of hydrocortisone to the intact and adrenalectomized animals led to increase of the enzyme activity in the tissues under study; the effect of hydrocortisone action depended on the initial hormonal background in the organism and the duration of the hormone administration. A single ACTH administration to the intact rabbits was accompanied by increase in the enzyme activity in the liver and the spleen, whereas to the adrenalectomized animals--in the brain, muscles and the blood plasma. A repeated administration of both hormones decreased the enzyme activity in the brain and the liver."}
{"id": "PMID:15247", "title": "A monomeric form of pyruvate kinase in human pyruvate kinase deficiency.", "content": "A mutant pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from human erythrocytes which is easily separated into monomers and dimers by gel chromatography is described. Tht mutant enzyme shows almost the same pH optimum and thermostability as normal enzyme, but has a decreased stability on shaking with air, a decreased Km for phosphoenolpyruvate and a loss of allosteric properties. The apparent Km values for phosphoenolpyruvate of tetramers and monomers were the same. The tetrameric enzyme was slightly activated by fructose-1,6-diphosphate but the monomeric form was not. The tetrameric enzyme was found to dissociate spontaneously to dimeric and monomeric forms.", "contents": "A monomeric form of pyruvate kinase in human pyruvate kinase deficiency. A mutant pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from human erythrocytes which is easily separated into monomers and dimers by gel chromatography is described. Tht mutant enzyme shows almost the same pH optimum and thermostability as normal enzyme, but has a decreased stability on shaking with air, a decreased Km for phosphoenolpyruvate and a loss of allosteric properties. The apparent Km values for phosphoenolpyruvate of tetramers and monomers were the same. The tetrameric enzyme was slightly activated by fructose-1,6-diphosphate but the monomeric form was not. The tetrameric enzyme was found to dissociate spontaneously to dimeric and monomeric forms."}
{"id": "PMID:15248", "title": "Membrane-associated assembly of M13 phage in extracts of virus-infected Escherichia coli.", "content": "Assembly of coliphage M13 is known to occur as the viral DNA crosses the cytoplasmic membrane, shedding its virus-coded DNA unwinding protein and acquiring from the membrane approximately 2400 copies of the major coat protein. Conditions are described in which extracts of M13-infected E. coli and membranes prepared from such extracts will support virus assembly at a rate equivalent to that of intact cells. Extracts prepared from cells infected with temperature-sensitive M13 mutants in genes 1, 3, 4, or 5 are temperature-sensitive in this cell-free assembly reaction. Phage assembly in vitro requires magnesium and as yet an unidentified heat-stable cofactor of low molecular weight. The rate of virus assembly is approximately linear with respect to extract concentration over a 10(4)-fold range, consistent with the observation that the entire M13 assembly activity copurifies with the cell membrane fraction.", "contents": "Membrane-associated assembly of M13 phage in extracts of virus-infected Escherichia coli. Assembly of coliphage M13 is known to occur as the viral DNA crosses the cytoplasmic membrane, shedding its virus-coded DNA unwinding protein and acquiring from the membrane approximately 2400 copies of the major coat protein. Conditions are described in which extracts of M13-infected E. coli and membranes prepared from such extracts will support virus assembly at a rate equivalent to that of intact cells. Extracts prepared from cells infected with temperature-sensitive M13 mutants in genes 1, 3, 4, or 5 are temperature-sensitive in this cell-free assembly reaction. Phage assembly in vitro requires magnesium and as yet an unidentified heat-stable cofactor of low molecular weight. The rate of virus assembly is approximately linear with respect to extract concentration over a 10(4)-fold range, consistent with the observation that the entire M13 assembly activity copurifies with the cell membrane fraction."}
{"id": "PMID:15249", "title": "Catecholamine binding to the beta-adrenergic receptor.", "content": "The adenylate cyclase-coupled beta-adrenergic receptors of frog erythrocyte membranes have been identified by direct radioligand binding techniques using the potent catecholamine agonist (+/-)[3H]hydroxybenzylisproterenol (2-[3, 4-dihydroxyphenyl]-2-hydroxy-1', 1'-dimethyl-2'-[4-hydroxyphenyl]-diethylamine). The successful experimental conditions included the use of (i) high concentrations of catechol and ascorbic acid to suppress nonreceptor binding, (ii) a very potent radiolabeled catecholamine (10 times more potent than isoproterenol), and (iii) membranes rich in binding sites for beta-adrenergic receptors. Thus, previous problems in accomplishing successful catecholamine binding to the beta-receptors have been overcome. The binding sites identified with (+/-)[3H]hydroxybenzylisoproterenol in the erythrocyte membranes have all the characteristics expected of true beta-adrenergic receptors. These include rapidity of binding, saturability, specificity for beta-agonists and antagonists, and stereospecificity [(-)isomers more potent than (+)isomers]. Physiologically inactive compounds containing a catechol moiety do not compete for occupancy of these binding sites. Dissociation of the radiolabeled agonist from the receptors is slow and incomplete in the absence of guanine nucleotides. In the presence of nucleotide, however, dissociation is rapid and complete. beta-Adrenergic agonists and antagonists compete for the (+/-)[3H]hydroxybenzylisoproterenol binding sites in a fashion parallel to their competition for the receptors, as previously delineated with the beta-adrenergic antagonist (-)[3H]dihydroalprenolol.", "contents": "Catecholamine binding to the beta-adrenergic receptor. The adenylate cyclase-coupled beta-adrenergic receptors of frog erythrocyte membranes have been identified by direct radioligand binding techniques using the potent catecholamine agonist (+/-)[3H]hydroxybenzylisproterenol (2-[3, 4-dihydroxyphenyl]-2-hydroxy-1', 1'-dimethyl-2'-[4-hydroxyphenyl]-diethylamine). The successful experimental conditions included the use of (i) high concentrations of catechol and ascorbic acid to suppress nonreceptor binding, (ii) a very potent radiolabeled catecholamine (10 times more potent than isoproterenol), and (iii) membranes rich in binding sites for beta-adrenergic receptors. Thus, previous problems in accomplishing successful catecholamine binding to the beta-receptors have been overcome. The binding sites identified with (+/-)[3H]hydroxybenzylisoproterenol in the erythrocyte membranes have all the characteristics expected of true beta-adrenergic receptors. These include rapidity of binding, saturability, specificity for beta-agonists and antagonists, and stereospecificity [(-)isomers more potent than (+)isomers]. Physiologically inactive compounds containing a catechol moiety do not compete for occupancy of these binding sites. Dissociation of the radiolabeled agonist from the receptors is slow and incomplete in the absence of guanine nucleotides. In the presence of nucleotide, however, dissociation is rapid and complete. beta-Adrenergic agonists and antagonists compete for the (+/-)[3H]hydroxybenzylisoproterenol binding sites in a fashion parallel to their competition for the receptors, as previously delineated with the beta-adrenergic antagonist (-)[3H]dihydroalprenolol."}
{"id": "PMID:15250", "title": "Trans-synaptic induction of adrenomedullary tyrosine hydroxylase activity by choline: evidence that choline administration can increase cholinergic transmission.", "content": "Twenty-four hours after rats receive choline chloride (20 mmol/kg, by stomach tube) the activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] increases by 31% within adrenomedullary chromaffin cells. This treatment also causes major elevations in the levels of choline and acetylcholine within the adrenal gland; however, acetylcholine levels return to normal by 16 hr after the choline is given. The daily administration of 10 or 20 mmol/kg of choline for 4 days elevates adrenal tyrosine hydroxylase activity by 29% or 51%, respectively. Such increases in tyrosine hydroxylase activity are not observed in animals given ammonium chloride, another basic chloride-containing compound, by stomach tube or in animals treated with cycloheximide, an inhibitor of adrenal protein synthesis. They are also absent in denervated adrenals. These observations demonstrate that the increase in presynaptic acetylcholine levels produced by giving animals the neurotransmitter's precursor (choline) can be associated with parallel changes in the transmission of signals across cholinergic synapses, probably because more of the transmitter is released per nerve impulse.", "contents": "Trans-synaptic induction of adrenomedullary tyrosine hydroxylase activity by choline: evidence that choline administration can increase cholinergic transmission. Twenty-four hours after rats receive choline chloride (20 mmol/kg, by stomach tube) the activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] increases by 31% within adrenomedullary chromaffin cells. This treatment also causes major elevations in the levels of choline and acetylcholine within the adrenal gland; however, acetylcholine levels return to normal by 16 hr after the choline is given. The daily administration of 10 or 20 mmol/kg of choline for 4 days elevates adrenal tyrosine hydroxylase activity by 29% or 51%, respectively. Such increases in tyrosine hydroxylase activity are not observed in animals given ammonium chloride, another basic chloride-containing compound, by stomach tube or in animals treated with cycloheximide, an inhibitor of adrenal protein synthesis. They are also absent in denervated adrenals. These observations demonstrate that the increase in presynaptic acetylcholine levels produced by giving animals the neurotransmitter's precursor (choline) can be associated with parallel changes in the transmission of signals across cholinergic synapses, probably because more of the transmitter is released per nerve impulse."}
{"id": "PMID:15251", "title": "Ionic regulation in genetic translation systems.", "content": "The polyelectrolyte theory can provide an interpretation of the interdependence of pH, ionic strength, and polyamines one observes in the activity of ribonuclease acting on RNA. According to this theory: (i) A nucleic acid-enzyme complex and the suspending medium may be considered as two phases in equilibrium, even though within limits, the complex is soluble in water. (ii) The enzymatic catalysis is under tight control of the electrostatic potential generated by the system. Consequently, modification in electrostatic potential will induce a concomitant change in activity. (iii) The electrostatic potential can be modified through action on the system of \"modulators\", either \"external\" (ionic strength, pH, temperature, etc.) or \"internal\" (specific ligands, substrates, protein factors, etc.). Similarities between the reaction of ribonuclease (ribonuclease 3'-pyrimidino-oligonucleotidohydrolase; EC 3.1.4.22) and RNA and those observed with highly organized systems catalyzing DNA, RNA, and protein synthesis suggest that the electrostatic potential also provides an important regulatory mechanism in genetic translation. In this view, an essential function of nucleic acids is to provide their enzyme partners with polyanionic microenvironments within which their catalytic activities are controlled by variation in physicochemical parameters, including the proton concentration induced through \"modulation\" of the local electrostatic potential.", "contents": "Ionic regulation in genetic translation systems. The polyelectrolyte theory can provide an interpretation of the interdependence of pH, ionic strength, and polyamines one observes in the activity of ribonuclease acting on RNA. According to this theory: (i) A nucleic acid-enzyme complex and the suspending medium may be considered as two phases in equilibrium, even though within limits, the complex is soluble in water. (ii) The enzymatic catalysis is under tight control of the electrostatic potential generated by the system. Consequently, modification in electrostatic potential will induce a concomitant change in activity. (iii) The electrostatic potential can be modified through action on the system of \"modulators\", either \"external\" (ionic strength, pH, temperature, etc.) or \"internal\" (specific ligands, substrates, protein factors, etc.). Similarities between the reaction of ribonuclease (ribonuclease 3'-pyrimidino-oligonucleotidohydrolase; EC 3.1.4.22) and RNA and those observed with highly organized systems catalyzing DNA, RNA, and protein synthesis suggest that the electrostatic potential also provides an important regulatory mechanism in genetic translation. In this view, an essential function of nucleic acids is to provide their enzyme partners with polyanionic microenvironments within which their catalytic activities are controlled by variation in physicochemical parameters, including the proton concentration induced through \"modulation\" of the local electrostatic potential."}
{"id": "PMID:15252", "title": "Catecholamine hormone receptor differences identified on 3T3 and simian virus-transformed 3T3 cells.", "content": "Identification and characterization of hormone receptors on the cell surface is an effective tool for studying the plasma membrane. Using the direct binding of a radiolabeled antagonist, (-)[3H]alprenolol, to crude membrane preparations, and a physiological response (cellular cyclic AMP levels), I demonstrated a catecholamine (beta-adrenergic) hormone receptor site coupled to a catecholamine responsive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] on 3T3 and simian virus 40 (SV40)-transformed 3T3 cells. At a concentration of 1 muM, epinephrine and isoproterenol elevate cellular cyclic AMP levels 8- and 12-fold, respectively, in both cell lines. Norepinephrine was also a potent agonist on 3T3 cells (8-fold stimulation), but SV3T3 cells showed a lesser (2-fold) response to this hormone. The specificity of the physiological response (as well as the direct binding studies using the alprenolol radiolabel) is indicated by the increased effectiveness of (-) compared to (+) stereoisomers, rapid and reversible kinetics (steady state within 2 min), high affinity (Kd approximately 30 nM) and saturability (indicating a finite number of hormone receptors). These hormone receptor studies indicate the 3T3 cells have a beta1 adrenergic receptor while the SV3T3 cells have a receptor with beta2 qualities. In addition, the number of beta-adrenergic hormone receptors appear to be increased in the normal 3T3 cells by approximately 2-fold over the SV3T3 cells (300 versus versus 120 femtomol/mg of protein).", "contents": "Catecholamine hormone receptor differences identified on 3T3 and simian virus-transformed 3T3 cells. Identification and characterization of hormone receptors on the cell surface is an effective tool for studying the plasma membrane. Using the direct binding of a radiolabeled antagonist, (-)[3H]alprenolol, to crude membrane preparations, and a physiological response (cellular cyclic AMP levels), I demonstrated a catecholamine (beta-adrenergic) hormone receptor site coupled to a catecholamine responsive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] on 3T3 and simian virus 40 (SV40)-transformed 3T3 cells. At a concentration of 1 muM, epinephrine and isoproterenol elevate cellular cyclic AMP levels 8- and 12-fold, respectively, in both cell lines. Norepinephrine was also a potent agonist on 3T3 cells (8-fold stimulation), but SV3T3 cells showed a lesser (2-fold) response to this hormone. The specificity of the physiological response (as well as the direct binding studies using the alprenolol radiolabel) is indicated by the increased effectiveness of (-) compared to (+) stereoisomers, rapid and reversible kinetics (steady state within 2 min), high affinity (Kd approximately 30 nM) and saturability (indicating a finite number of hormone receptors). These hormone receptor studies indicate the 3T3 cells have a beta1 adrenergic receptor while the SV3T3 cells have a receptor with beta2 qualities. In addition, the number of beta-adrenergic hormone receptors appear to be increased in the normal 3T3 cells by approximately 2-fold over the SV3T3 cells (300 versus versus 120 femtomol/mg of protein)."}
{"id": "PMID:15253", "title": "Genetic control of renin activity in the submaxillary gland of the mouse.", "content": "Administration of androgen to female mice is known to increase the level of several proteins in the submaxillary gland, including nerve growth factor, epidermal growth factor, esteroproteolytic activity, and renin. In the present study, renin activity has been assessed in extracts of submaxillary gland of female mice from two inbred strains (SWR/J and C57BL/10J), from F1 and F2 hybrids, and from backcrosses between F1 and parental strains. In both uninduced and induced mice, renin activity of submaxillary gland was more than 100-fold greater in SWR/J than in C57BL/10J mice as measured by either an enzymatic assay or an immunodiffusion method. This difference was not due to differences in plasma testosterone levels between the strains, and the enzymes from the two strains had similar pH optima, substrate specificities, heat stabilities, and apparent Michaelis constants. In the submaxillary gland the difference was relatively specific for renin because increases in esteroproteolytic activity, nerve growth factor, and epidermal growth factor after androgen treatment appeared to be similar in both strains. Studies with the various hybrids indicate that the difference in renin activity between the two strains is apparently due to a single regulatory gene.", "contents": "Genetic control of renin activity in the submaxillary gland of the mouse. Administration of androgen to female mice is known to increase the level of several proteins in the submaxillary gland, including nerve growth factor, epidermal growth factor, esteroproteolytic activity, and renin. In the present study, renin activity has been assessed in extracts of submaxillary gland of female mice from two inbred strains (SWR/J and C57BL/10J), from F1 and F2 hybrids, and from backcrosses between F1 and parental strains. In both uninduced and induced mice, renin activity of submaxillary gland was more than 100-fold greater in SWR/J than in C57BL/10J mice as measured by either an enzymatic assay or an immunodiffusion method. This difference was not due to differences in plasma testosterone levels between the strains, and the enzymes from the two strains had similar pH optima, substrate specificities, heat stabilities, and apparent Michaelis constants. In the submaxillary gland the difference was relatively specific for renin because increases in esteroproteolytic activity, nerve growth factor, and epidermal growth factor after androgen treatment appeared to be similar in both strains. Studies with the various hybrids indicate that the difference in renin activity between the two strains is apparently due to a single regulatory gene."}
{"id": "PMID:15254", "title": "Alterations of spore coat processing and protein turnover in a Bacillus cereus mutant with a defective postexponential intracellular protease.", "content": "A mutant with an alteration in the major intracellular serine protease produced by postexponential Bacillus cereus was isolated by screening mutants defective in spore germination. The purified enzyme from the mutant is more labile to heat and alkaline pH than the protease from the wild type. Protease activity appears at the same time as in the wild type but only reaches 50% of the specific activity and decays more rapidly during sporulation. Coincident with the decay is a decrease in the rate of protein turnover. Generation of amino acids by turnover seems to be important for sporulation because the number of spores produced by the mutant is increased 4- to 10-fold by addition of casamino acids. As anticipated, the mutant produces spores that germinate poorly but, surprisingly, these spores are very deficient in coat protein. Coat antigen is present in cell extracts of mutant and wild type, however, both as large molecules not found on mature spores and as spore coat protein monomers. The large molecules rapidly disappear in a pulse chase experiment in the wild type with some increase in the coat monomers. In mutant extracts, however, this large coat antigen is slowly and improperly processed.", "contents": "Alterations of spore coat processing and protein turnover in a Bacillus cereus mutant with a defective postexponential intracellular protease. A mutant with an alteration in the major intracellular serine protease produced by postexponential Bacillus cereus was isolated by screening mutants defective in spore germination. The purified enzyme from the mutant is more labile to heat and alkaline pH than the protease from the wild type. Protease activity appears at the same time as in the wild type but only reaches 50% of the specific activity and decays more rapidly during sporulation. Coincident with the decay is a decrease in the rate of protein turnover. Generation of amino acids by turnover seems to be important for sporulation because the number of spores produced by the mutant is increased 4- to 10-fold by addition of casamino acids. As anticipated, the mutant produces spores that germinate poorly but, surprisingly, these spores are very deficient in coat protein. Coat antigen is present in cell extracts of mutant and wild type, however, both as large molecules not found on mature spores and as spore coat protein monomers. The large molecules rapidly disappear in a pulse chase experiment in the wild type with some increase in the coat monomers. In mutant extracts, however, this large coat antigen is slowly and improperly processed."}
{"id": "PMID:15255", "title": "Dehydrogenase and transhydrogenase properties of the soluble NADH dehydrogenase of bovine heart mitochondria.", "content": "The soluble NADH dehydrogenase of low molecular weight, isolated from complex I (NADH:ubiquinone oxidoreductase, EC 1.6.5.3) of the respiratory chain, has been shown to have NADPH dehydrogenase and NADPH leads to NAD transhydrogenase activities. Both activities are greatly increased in the presence of added guanidine-HCl and at pH values less than 6.5. The chromophores of the soluble enzyme (flavin and iron--sulfur centers) are reduced by NADH and NADPH to the same extent. The latter reduction is extremely slow, and is considerably stimulated in the presence of guanidine-HCl. The soluble dehydrogenase has little or no NADH leads to NADP and NADPH leads to NADP transhydrogenase activity. The former reaction is known to be energy-linked in submitochondrial particles; the latter was shown in the present studies also to be energy-linked. In view of the above and earlier results, possible mechanisms for dehydrogenation and transhydrogenation (nonenergy-linked and energy-linked) involving reduced and oxidized NAD and NADP are proposed.", "contents": "Dehydrogenase and transhydrogenase properties of the soluble NADH dehydrogenase of bovine heart mitochondria. The soluble NADH dehydrogenase of low molecular weight, isolated from complex I (NADH:ubiquinone oxidoreductase, EC 1.6.5.3) of the respiratory chain, has been shown to have NADPH dehydrogenase and NADPH leads to NAD transhydrogenase activities. Both activities are greatly increased in the presence of added guanidine-HCl and at pH values less than 6.5. The chromophores of the soluble enzyme (flavin and iron--sulfur centers) are reduced by NADH and NADPH to the same extent. The latter reduction is extremely slow, and is considerably stimulated in the presence of guanidine-HCl. The soluble dehydrogenase has little or no NADH leads to NADP and NADPH leads to NADP transhydrogenase activity. The former reaction is known to be energy-linked in submitochondrial particles; the latter was shown in the present studies also to be energy-linked. In view of the above and earlier results, possible mechanisms for dehydrogenation and transhydrogenation (nonenergy-linked and energy-linked) involving reduced and oxidized NAD and NADP are proposed."}
{"id": "PMID:15256", "title": "31P nuclear magnetic resonance studies of glycogen phosphorylase from rabbit skeletal muscle: ionization states of pyridoxal 5'-phosphate.", "content": "31P nuclear magnetic resonance (NMR) at 72.8 MHZ has been used to study glycogen phosphorylase from rabbit muscle (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase, EC 2.4.1.1) at concentrations as low as 25 mg/ml, using a WH-180 wide-bore superconducting spectrometer. The use of a thio analogue for 5'-AMP and arsenate for inorganic phosphate allowed the observation of three distinct forms of enzyme-bound pyridoxal 5'-phosphate at --0.2 ppm (Form I), --2 to --3 ppm (Form II), and --3.5 ppm (Form III) relative to triethylphosphate. Conversion of I to III occurs by activation of phosphorylase either by formation of a ternary complex of phosphorylase b with effector and arsenate or, more efficiently, by direct phosphorylation to give the a form of the enzyme. The ionization state and exposure to solvent of each of the three forms is inferred from the 31P NMR data.", "contents": "31P nuclear magnetic resonance studies of glycogen phosphorylase from rabbit skeletal muscle: ionization states of pyridoxal 5'-phosphate. 31P nuclear magnetic resonance (NMR) at 72.8 MHZ has been used to study glycogen phosphorylase from rabbit muscle (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase, EC 2.4.1.1) at concentrations as low as 25 mg/ml, using a WH-180 wide-bore superconducting spectrometer. The use of a thio analogue for 5'-AMP and arsenate for inorganic phosphate allowed the observation of three distinct forms of enzyme-bound pyridoxal 5'-phosphate at --0.2 ppm (Form I), --2 to --3 ppm (Form II), and --3.5 ppm (Form III) relative to triethylphosphate. Conversion of I to III occurs by activation of phosphorylase either by formation of a ternary complex of phosphorylase b with effector and arsenate or, more efficiently, by direct phosphorylation to give the a form of the enzyme. The ionization state and exposure to solvent of each of the three forms is inferred from the 31P NMR data."}
{"id": "PMID:15257", "title": "High-resolution 31P nuclear magnetic resonance studies of metabolism in aerobic Escherichia coli cells.", "content": "31P nuclear magnetic resonance spectra at 145.7 MHZ were obtained of concentrated suspensions of E. coli cells. The position of the Pi resonance was used to determine the pH, and in most experiments it was possible to distinguish the intracellular (pHin) and extracellular (pHex) values. During respiration pHin approached 7.55, while pHex varied from 6.0 to 8.0. With succinate as a carbon source and in a N2 environment, pHin - pHex. Upon addition of glucose, pHin greater than pHex. In the presence of an ATPase (adenosinetriphosphatase; ATP phosphohydrolase; EC 3.6.1.3) inhibitor dicyclohexylcarbodiimide, pHin remained equal to pHex even in the presence of glucose. In other experiments, oxygenation brought pHin above pHex even in the presence of dicyclohexylcarbodiimide. These experiments are consistent with Mitchell's hypothesis that, first, delta pH can be created by the reversal of the ATPase reaction and, second, that protons are pumped outward during respiration. In addition to Pi, about 10 more resonances were resolved, several of which were assigned to different phosphate metabolites.", "contents": "High-resolution 31P nuclear magnetic resonance studies of metabolism in aerobic Escherichia coli cells. 31P nuclear magnetic resonance spectra at 145.7 MHZ were obtained of concentrated suspensions of E. coli cells. The position of the Pi resonance was used to determine the pH, and in most experiments it was possible to distinguish the intracellular (pHin) and extracellular (pHex) values. During respiration pHin approached 7.55, while pHex varied from 6.0 to 8.0. With succinate as a carbon source and in a N2 environment, pHin - pHex. Upon addition of glucose, pHin greater than pHex. In the presence of an ATPase (adenosinetriphosphatase; ATP phosphohydrolase; EC 3.6.1.3) inhibitor dicyclohexylcarbodiimide, pHin remained equal to pHex even in the presence of glucose. In other experiments, oxygenation brought pHin above pHex even in the presence of dicyclohexylcarbodiimide. These experiments are consistent with Mitchell's hypothesis that, first, delta pH can be created by the reversal of the ATPase reaction and, second, that protons are pumped outward during respiration. In addition to Pi, about 10 more resonances were resolved, several of which were assigned to different phosphate metabolites."}
{"id": "PMID:15258", "title": "Intracellular binding of radioactive hydroxocobalamin to cobalamin-dependent apoenzymes in rat liver.", "content": "We identified previously an intracellular cobalamin (Cbl) binding protein(s) in cultured human fibroblasts, distinct from known Cbl \"R\" binders and absent from mutant cells deficient in the synthesis of the two Cbl coenzymes. In order to further characterize this binding activity, we have investigated its homologue in rat liver. After being transported to the liver by the serum protein transcobalamin II, [57Co]Cbl was bound by at least two distinct proteins, one cytosolic, the other mitochondrial. Labeled Cbl bound to cytosolic protein faster than or prior to the mitochondrial protein. With time there was a decline in radioactivity associated with the cytosolic binder and a coordinate increase in that associated with the mitochondrial binder. Although both proteins cochromatographed on Sephadex G-150 and had apparent molecular weights of 120,000, they were separated into two discrete components by polyacrylamide gel electrophoresis and by DEAE-cellulose chromatography. The cytosolic binder cochromatographed with N5-methyltetrahydrofolate:homocysteine methyltransferase activity (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13); the mitochondrial one with methylmalonyl CoA mutase activity (methylmalonyl-CoA CoA-carbonylmutase, EC 5.4.99.2). These proteins were distinguished further by the chemical forms of [57Co]Cbl found with them, hydroxocobalamin and methylcobalamin with the cytosolic protein and adenosylcobalamin with the mitochondrial one. These results suggest that intracellular Cbl binding activity in rat liver can be accounted for by attachment of Cbl to the two known Cbl-dependent apoenzymes, methylmalonyl CoA mutase and methyltetrahydrofolate methyltransferase. The mechanism and significance of the observered binding protein deficiency in mutant human fibroblasts must, therefore, be re-evaluated.", "contents": "Intracellular binding of radioactive hydroxocobalamin to cobalamin-dependent apoenzymes in rat liver. We identified previously an intracellular cobalamin (Cbl) binding protein(s) in cultured human fibroblasts, distinct from known Cbl \"R\" binders and absent from mutant cells deficient in the synthesis of the two Cbl coenzymes. In order to further characterize this binding activity, we have investigated its homologue in rat liver. After being transported to the liver by the serum protein transcobalamin II, [57Co]Cbl was bound by at least two distinct proteins, one cytosolic, the other mitochondrial. Labeled Cbl bound to cytosolic protein faster than or prior to the mitochondrial protein. With time there was a decline in radioactivity associated with the cytosolic binder and a coordinate increase in that associated with the mitochondrial binder. Although both proteins cochromatographed on Sephadex G-150 and had apparent molecular weights of 120,000, they were separated into two discrete components by polyacrylamide gel electrophoresis and by DEAE-cellulose chromatography. The cytosolic binder cochromatographed with N5-methyltetrahydrofolate:homocysteine methyltransferase activity (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13); the mitochondrial one with methylmalonyl CoA mutase activity (methylmalonyl-CoA CoA-carbonylmutase, EC 5.4.99.2). These proteins were distinguished further by the chemical forms of [57Co]Cbl found with them, hydroxocobalamin and methylcobalamin with the cytosolic protein and adenosylcobalamin with the mitochondrial one. These results suggest that intracellular Cbl binding activity in rat liver can be accounted for by attachment of Cbl to the two known Cbl-dependent apoenzymes, methylmalonyl CoA mutase and methyltetrahydrofolate methyltransferase. The mechanism and significance of the observered binding protein deficiency in mutant human fibroblasts must, therefore, be re-evaluated."}
{"id": "PMID:15259", "title": "Recognition of two intracellular cobalamin binding proteins and their identification as methylmalonyl-CoA mutase and methionine synthetase.", "content": "The granulocyte R-type cobalamin binding protein delivers cobalamin (Cbl) exclusively to hepatocytes, and transcobalamin II delivers Cbl to various mammalian cells. Both protein-Cbl complexes enter cells by pinocytosis, and the protein moieties are rapidly degraded in lysosomes. The liberated Cbl is subsequently bound to a high-molecular-weight intracellular cobalamin binding protein (ICB). The nature of ICB-Cbl is unknown but appears important because ICB-[57Co]Cbl is missing from cultured fibroblasts of a group of patients whose cells take up CN-[57Co]Cbl normally but do not convert it to either of its coenzyme forms. We have examined supernatants of sonicated rabbit livers and have found that 65% of the total endogenous Cbl elutes from Sephadex G-150 as ICB-Cbl and that this fraction also contains the two mammalian Cbl-dependent enzymes, methylmalonyl-CoA mutase (methylmalonyl-CoA CoA-carbonylmutase;EC 5.4.99.2) and methionine synthetase (tetrahydropteroylglutamate methyltransferase; 5-methyltetrahydropteroyl-L-glutamate:L-homocysteine-S-methyltransferase; EC 2.1.1.13). Gradient elution from DEAE-Sephadex reveals that 90--95% of the ICB--Cbl elutes with methylmalonyl-CoA mutase and 5--10% elutes with methionine synthetase. ICB--[57Co]Cbl first appears 2 hr after the intravenous injection of CN[57Co]Cbl bound to granulocyte R-type protein. This ICB-[57Co]Cbl is associated with either methylmalonyl-CoA mutase or methionine synthetase although the latter appears to be formed at a relatively faster rate. Our studies indicate that mammalian cells contain two ICBs, that these proteins are methylmalonyl-CoA mutase and methionine synthetase, and that the primary abnormality in the group of patients mentioned above lies at a step that is common to the formation of both Cbl coenzymes and that precedes the stable binding of Cbl to both methylmalonyl-CoA mutase and methionine synthetase.", "contents": "Recognition of two intracellular cobalamin binding proteins and their identification as methylmalonyl-CoA mutase and methionine synthetase. The granulocyte R-type cobalamin binding protein delivers cobalamin (Cbl) exclusively to hepatocytes, and transcobalamin II delivers Cbl to various mammalian cells. Both protein-Cbl complexes enter cells by pinocytosis, and the protein moieties are rapidly degraded in lysosomes. The liberated Cbl is subsequently bound to a high-molecular-weight intracellular cobalamin binding protein (ICB). The nature of ICB-Cbl is unknown but appears important because ICB-[57Co]Cbl is missing from cultured fibroblasts of a group of patients whose cells take up CN-[57Co]Cbl normally but do not convert it to either of its coenzyme forms. We have examined supernatants of sonicated rabbit livers and have found that 65% of the total endogenous Cbl elutes from Sephadex G-150 as ICB-Cbl and that this fraction also contains the two mammalian Cbl-dependent enzymes, methylmalonyl-CoA mutase (methylmalonyl-CoA CoA-carbonylmutase;EC 5.4.99.2) and methionine synthetase (tetrahydropteroylglutamate methyltransferase; 5-methyltetrahydropteroyl-L-glutamate:L-homocysteine-S-methyltransferase; EC 2.1.1.13). Gradient elution from DEAE-Sephadex reveals that 90--95% of the ICB--Cbl elutes with methylmalonyl-CoA mutase and 5--10% elutes with methionine synthetase. ICB--[57Co]Cbl first appears 2 hr after the intravenous injection of CN[57Co]Cbl bound to granulocyte R-type protein. This ICB-[57Co]Cbl is associated with either methylmalonyl-CoA mutase or methionine synthetase although the latter appears to be formed at a relatively faster rate. Our studies indicate that mammalian cells contain two ICBs, that these proteins are methylmalonyl-CoA mutase and methionine synthetase, and that the primary abnormality in the group of patients mentioned above lies at a step that is common to the formation of both Cbl coenzymes and that precedes the stable binding of Cbl to both methylmalonyl-CoA mutase and methionine synthetase."}
{"id": "PMID:15260", "title": "Affinity labeling of gamma-glutamyl transpeptidase and location of the gamma-glutamyl binding site on the light subunit.", "content": "Gamma-Glutamyl transpeptidase, which consists of two nonidentical subunits, is rapidly inactivated with respect to its transpeptidase and hydrolase activities by the gamma-glutamyl analogs 6-diazo-5-oxo-L-norleucine and L-azaserine. Inactivation, which is prevented by gamma-glutamyl substrates (but not by acceptor substrates), is accelerated by maleate, which was previously shown to enhance utilization of glutamine by transpeptidase. 6-Diazo-5-oxo--norleucine reacts specifically, covalently, and stoichiometrically at the gamma-glutamyl site of the enzyme, which was localized through studies with 6-diazo-5-OXO-[14C]norleucine to the light subunits of both the transpeptidase of rat kidney (which has subunits of molecular weights 22,000 and 46,000) and the transpeptidase of human kidney (which has subunits of molecular weights 22,000 and 62,000). The findings, which indicate that these enzymes have similar gamma-glutamyl binding subunits, are relevant to the structure-function relationships of this membrane-bound enzyme and its physiological role.", "contents": "Affinity labeling of gamma-glutamyl transpeptidase and location of the gamma-glutamyl binding site on the light subunit. Gamma-Glutamyl transpeptidase, which consists of two nonidentical subunits, is rapidly inactivated with respect to its transpeptidase and hydrolase activities by the gamma-glutamyl analogs 6-diazo-5-oxo-L-norleucine and L-azaserine. Inactivation, which is prevented by gamma-glutamyl substrates (but not by acceptor substrates), is accelerated by maleate, which was previously shown to enhance utilization of glutamine by transpeptidase. 6-Diazo-5-oxo--norleucine reacts specifically, covalently, and stoichiometrically at the gamma-glutamyl site of the enzyme, which was localized through studies with 6-diazo-5-OXO-[14C]norleucine to the light subunits of both the transpeptidase of rat kidney (which has subunits of molecular weights 22,000 and 46,000) and the transpeptidase of human kidney (which has subunits of molecular weights 22,000 and 62,000). The findings, which indicate that these enzymes have similar gamma-glutamyl binding subunits, are relevant to the structure-function relationships of this membrane-bound enzyme and its physiological role."}
{"id": "PMID:15261", "title": "Detection in bovine adrenal cortex of a lipoidal substance that yields pregnenolone upon treatment with alkali.", "content": "Bovine adrenal cortical tissue contains a lipoidal derivative of pregnenolone (3beta-hydroxy-pregn-5-en-20-one) from which the free steroid can be liberated by treatment with alkali. Evidence for the presence of such an entity comes from examination of a nonpolar extract of tissue from which pregnenolone and its sulfate had been removed by chromatography. Treatment of the nonpolar fraction with alkali followed by exhaustive chromatographic analysis led to the detection of pregnenolone. The steroid was identified by both gas chromatography/mass spectrometry and double isotope procedures. Quantitative analysis indicated that the three forms of pregnenolone are present in bovine adrenal cortical tissue in the following amounts (mug/kg): lipoidal derivative, 290; free steroid, 435; and sulfate, 65. Because the only known metabolic function of pregnenolone is to serve as a precursor of the steroid hormones, these findings have far-reaching implications for steroid hormone biochemistry.", "contents": "Detection in bovine adrenal cortex of a lipoidal substance that yields pregnenolone upon treatment with alkali. Bovine adrenal cortical tissue contains a lipoidal derivative of pregnenolone (3beta-hydroxy-pregn-5-en-20-one) from which the free steroid can be liberated by treatment with alkali. Evidence for the presence of such an entity comes from examination of a nonpolar extract of tissue from which pregnenolone and its sulfate had been removed by chromatography. Treatment of the nonpolar fraction with alkali followed by exhaustive chromatographic analysis led to the detection of pregnenolone. The steroid was identified by both gas chromatography/mass spectrometry and double isotope procedures. Quantitative analysis indicated that the three forms of pregnenolone are present in bovine adrenal cortical tissue in the following amounts (mug/kg): lipoidal derivative, 290; free steroid, 435; and sulfate, 65. Because the only known metabolic function of pregnenolone is to serve as a precursor of the steroid hormones, these findings have far-reaching implications for steroid hormone biochemistry."}
{"id": "PMID:15262", "title": "Regulation of hepatic nuclear guanylate cyclase.", "content": "In immunohistochemical studies of rat liver tissue slices and purified nuclei, adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) immunofluorescence on the nuclear membrane are sequentially increased after glucagon administration. An explanation for the increased cGMP immunofluorescence was sought in experiments in which guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2]activity of hepatic subcellular fractions was determined. The results showed that a nuclear guanylate cyclase exists which can be distinguished from the soluble and crude particulate guanylate cyclases. The activity of the nuclear enzyme was increased by 35% in nuclei isolated from rats 30 min after glucagon injection, the time at which maximal nuclear membrane cGMP immunofluorescence is observed. Because glucagon altered both cAMP location and levels prior to the observed changes in nuclear cGMP metabolism, the hypothesis that cAMP acted as the second messenger was tested. In vitro incubation of nuclei isolated from control rats with 10(-5) M cAMP produced a 25% increase in nuclear guanylate cyclase activity. With nuclei isolated from glucagon-treated rats, no significant increase in enzyme activity was observed; this indicates that maximal stimulation of nuclear guanylate cyclase by cAMP occurred at levels that are obtained in vivo after glucagon administration. These findings suggest that hepatic nuclear cGMP content may be regulated by a specific organelle guanylate cyclase and that cAMP may be one of the determinants of this enzyme's activity.", "contents": "Regulation of hepatic nuclear guanylate cyclase. In immunohistochemical studies of rat liver tissue slices and purified nuclei, adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) immunofluorescence on the nuclear membrane are sequentially increased after glucagon administration. An explanation for the increased cGMP immunofluorescence was sought in experiments in which guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2]activity of hepatic subcellular fractions was determined. The results showed that a nuclear guanylate cyclase exists which can be distinguished from the soluble and crude particulate guanylate cyclases. The activity of the nuclear enzyme was increased by 35% in nuclei isolated from rats 30 min after glucagon injection, the time at which maximal nuclear membrane cGMP immunofluorescence is observed. Because glucagon altered both cAMP location and levels prior to the observed changes in nuclear cGMP metabolism, the hypothesis that cAMP acted as the second messenger was tested. In vitro incubation of nuclei isolated from control rats with 10(-5) M cAMP produced a 25% increase in nuclear guanylate cyclase activity. With nuclei isolated from glucagon-treated rats, no significant increase in enzyme activity was observed; this indicates that maximal stimulation of nuclear guanylate cyclase by cAMP occurred at levels that are obtained in vivo after glucagon administration. These findings suggest that hepatic nuclear cGMP content may be regulated by a specific organelle guanylate cyclase and that cAMP may be one of the determinants of this enzyme's activity."}
{"id": "PMID:15263", "title": "Effect of batrachotoxin on the electroplax of electric eel: evidence for voltage-dependent interaction with sodium channels.", "content": "Batrachotoxin under certain conditions has a strong depolarizing effect on the innervated membrane of the monocellular electroplax preparation from the electric eel, El-ectrophorus electricus. No effect is observed when the toxin (50-200 nM) is applied to the resting membrane for periods up to 1 hr. However, if the membrane is exposed to batrachotoxin  and the cell is subjected to stimulation at a stimulus voltage slightly above the threshold for action potential firing, a progressive prolongation of the action potential and concomitant progressive depolarization of the innervated membrane is observed. When the membrane is depolarized by 15-20 mV, a further abrupt all-or-none depolarization occurs, and the potential attains a steady-state value between 0 and -10 mV. Brief stimulation of a cell in the presence of batrachotoxin is sufficient to define a batrachotoxin-treated cell, even though negligible depolarization occurs. If depolarizing agents such as carbamoylcholine or potassium chloride are introduced to such a cell in concentrations that normally produce a 20-30 mV depolarization, the abrupt all-or-none depolarization immediately occurs. All-or-none depolarizations arising from either electrical stimulation or depolarizing agents are unaffected by d-tubocurarine but are completely reversed by tetrodotoxin. Batrachotoxin thus appears to activate only the action potential sodium channels. In the batrachotoxin-treated membrane, these channels can attain stable steady states in either a closed configuration at the normal resting potential or in an open configuration after complete depolarization. A striking hysteresis cycle thus can be generated, which is strongly indicative of a voltage-dependent interaction of the toxin with the action potential sodium channels.", "contents": "Effect of batrachotoxin on the electroplax of electric eel: evidence for voltage-dependent interaction with sodium channels. Batrachotoxin under certain conditions has a strong depolarizing effect on the innervated membrane of the monocellular electroplax preparation from the electric eel, El-ectrophorus electricus. No effect is observed when the toxin (50-200 nM) is applied to the resting membrane for periods up to 1 hr. However, if the membrane is exposed to batrachotoxin  and the cell is subjected to stimulation at a stimulus voltage slightly above the threshold for action potential firing, a progressive prolongation of the action potential and concomitant progressive depolarization of the innervated membrane is observed. When the membrane is depolarized by 15-20 mV, a further abrupt all-or-none depolarization occurs, and the potential attains a steady-state value between 0 and -10 mV. Brief stimulation of a cell in the presence of batrachotoxin is sufficient to define a batrachotoxin-treated cell, even though negligible depolarization occurs. If depolarizing agents such as carbamoylcholine or potassium chloride are introduced to such a cell in concentrations that normally produce a 20-30 mV depolarization, the abrupt all-or-none depolarization immediately occurs. All-or-none depolarizations arising from either electrical stimulation or depolarizing agents are unaffected by d-tubocurarine but are completely reversed by tetrodotoxin. Batrachotoxin thus appears to activate only the action potential sodium channels. In the batrachotoxin-treated membrane, these channels can attain stable steady states in either a closed configuration at the normal resting potential or in an open configuration after complete depolarization. A striking hysteresis cycle thus can be generated, which is strongly indicative of a voltage-dependent interaction of the toxin with the action potential sodium channels."}
{"id": "PMID:15284", "title": "Phencyclidine-induced rotational behavior in rats with nigrostriatal lesions and its modulation by dopaminergic and cholinergic agents.", "content": "The peripheral administration of the psychotomimetic drug phencyclidine (1-(phenylcyclohexyl) piperidine hydrochloride) (PCP) induces a dose-related ipsilateral rotation in unilateral substantia nigra electrolytically-lesioned rats. The intensity of this rotation can be modulated by administration of various dopaminergic and cholinergic agents. Injection of alpha-methylparatyrosine methylester (125 mg/kg) or haloperidol (1 mg/kg) inhibited the ipsilateral circling behavior. Pimozide (1 mg/kg) also inhibitied the rotation, but to a lesser extent. The injection of the anticholinergic agent trihexyphenidyl (5 mg/kg) potentiated, and the cholinomimetic drug arecoline (5 mg/kg), depressed the rotation induced by PCP (7.5 mg/kg), It is probable that PCP possesses significant dopaminergic and anticholinergic properties. The capacity of PCP to induce rotation in this model may be related to its effects on dopaminergic and cholingergic neurons in the rat striatum. Thus, PCP may induce rotational behavior by potentiating dopaminergic transmission, by blocking cholinergic activity, or both; both of these effects have been demonstrated to be important in the generation of circling behavior in rats with nigrostriatal lesions.", "contents": "Phencyclidine-induced rotational behavior in rats with nigrostriatal lesions and its modulation by dopaminergic and cholinergic agents. The peripheral administration of the psychotomimetic drug phencyclidine (1-(phenylcyclohexyl) piperidine hydrochloride) (PCP) induces a dose-related ipsilateral rotation in unilateral substantia nigra electrolytically-lesioned rats. The intensity of this rotation can be modulated by administration of various dopaminergic and cholinergic agents. Injection of alpha-methylparatyrosine methylester (125 mg/kg) or haloperidol (1 mg/kg) inhibited the ipsilateral circling behavior. Pimozide (1 mg/kg) also inhibitied the rotation, but to a lesser extent. The injection of the anticholinergic agent trihexyphenidyl (5 mg/kg) potentiated, and the cholinomimetic drug arecoline (5 mg/kg), depressed the rotation induced by PCP (7.5 mg/kg), It is probable that PCP possesses significant dopaminergic and anticholinergic properties. The capacity of PCP to induce rotation in this model may be related to its effects on dopaminergic and cholingergic neurons in the rat striatum. Thus, PCP may induce rotational behavior by potentiating dopaminergic transmission, by blocking cholinergic activity, or both; both of these effects have been demonstrated to be important in the generation of circling behavior in rats with nigrostriatal lesions."}
{"id": "PMID:15285", "title": "Differential motor effects of intraventricular infusion of morphine and etonitazene.", "content": "The motor effects produced by intraventricular infusions of morphine were compared to the effects of etonitazene. Despite the similarity in the peripheral actions of these drugs, motor effects of central infusions differed dramatically. Intraventricular morphine infusions resulted in explosive motor behavior whereas etonitazene produced extreme muscular rigidity. The periaqueductal grey (PAG) has been proposed as the substrate of morphine-induced explosive motor behavior. However, considerations of the dose of morphine and the mobility of this drug in tissue suggests that sites other than the PAG may also be involved in explosive motor behavior.", "contents": "Differential motor effects of intraventricular infusion of morphine and etonitazene. The motor effects produced by intraventricular infusions of morphine were compared to the effects of etonitazene. Despite the similarity in the peripheral actions of these drugs, motor effects of central infusions differed dramatically. Intraventricular morphine infusions resulted in explosive motor behavior whereas etonitazene produced extreme muscular rigidity. The periaqueductal grey (PAG) has been proposed as the substrate of morphine-induced explosive motor behavior. However, considerations of the dose of morphine and the mobility of this drug in tissue suggests that sites other than the PAG may also be involved in explosive motor behavior."}
{"id": "PMID:15288", "title": "The different influence of predominantly antiadrenergic and antidopaminergic neuroleptics on the estrous cycle in rats.", "content": "In experiments performed on rats, single subcutaneous doses of predominantly antidopaminergic neuroleptics (fluspirilene, pimozide, and thioproperazine in large doses) elicited persistent diestrus, i.e. pseudopregnancy. Neuroleptics with predominantly antiadrenergic action (levomepromazine, thioridazine, chlorpromazine) as well as phenoxybenzamine injected intraventricularly induced mainly prolonged estrus, i.e. blocking of ovulation. Since pseudopregnancy implies a rise of prolactin secretion, our results indirectly indicate that PIF secretion is stimulated by dopamine. The antiovulatory effect of the antiadrenergic agents, which involves an inhibition of the proestral LH surge, suggests that the discharge of LRF is mediated by an adrenergic mechanism.", "contents": "The different influence of predominantly antiadrenergic and antidopaminergic neuroleptics on the estrous cycle in rats. In experiments performed on rats, single subcutaneous doses of predominantly antidopaminergic neuroleptics (fluspirilene, pimozide, and thioproperazine in large doses) elicited persistent diestrus, i.e. pseudopregnancy. Neuroleptics with predominantly antiadrenergic action (levomepromazine, thioridazine, chlorpromazine) as well as phenoxybenzamine injected intraventricularly induced mainly prolonged estrus, i.e. blocking of ovulation. Since pseudopregnancy implies a rise of prolactin secretion, our results indirectly indicate that PIF secretion is stimulated by dopamine. The antiovulatory effect of the antiadrenergic agents, which involves an inhibition of the proestral LH surge, suggests that the discharge of LRF is mediated by an adrenergic mechanism."}
{"id": "PMID:15290", "title": "The functional anatomy of the mantle complex and columellar muscle of tectibranch molluscs (Gastropoda: Opisthobranchia), and its bearing on the evolution of opisthobranch organization.", "content": "An account is given of the anatomy of a series of opisthobranch molluscs principally to assess the change in importance and functioning of the mantle cavity and columellar muscle throughout the transition from prosobranch to opisthobranch organization. Intermediate steps are represented by living tectibranchs, of which Philine and Scaphander are investigated in detail, Acteon, Bulla, Haminoea, Akera, Aglaja and Gastropteron more briefly. Though an opisthobranch, Acteon has an organization typical of a monotocardian prosobranch; the remainder show trends affecting the shell and visceral mass, mantle cavity and head-foot, which resulted finally in the production of nudibranch types. It is confirmed that the adaptations exhibited by primitive tectibranchs relate to the assumption of a burrowing mode of life. Initial changes were the reduction of the nuchal area and sealing of the mantle cavity anteriorly so that it opened on the right, where it became restricted, the first perhaps prompting the sealing. A broadening and an anterior elongation of the head-foot produced a wedge to facilitate burrowing. Change in disposition of the mantle edge, incurred by differential growth, produced an involute shell with a large body whorl, alignment changing from erect to horizontal. The resultant streamlining eased infaunal progression; no vertical insinking of the viscera was involved. Subsequently the shell became reduced and finally lost. A section of the mantle edge enlarged to produce a posterior mantle lobe upon which sit both the shell and viscera, and which later became redundant as posterior elongation of the head-foot produced a slug-like form, the viscera being incorporated within the head-foot. As the nuchal area became reduced, mechanical needs prompted alteration to both the form and attachment of the columellar muscle. In Acteon the muscle is like that of a prosobranch, but the proximal region has broadened, a change of proportion required by primitive tectibranchs in order to support the floor of the mantle cavity formed from the section of mantle skirt which in prosobranchs lies on the right. This was followed by reduction and re-alignment of the entire muscle along an anteroposterior axis as emphasis changed from the muscle effecting retraction into a shell to producing contorsions of the head-foot. The shell, similarly reduced, instead of providing anchorage, became itself anchored by additional anterior and posterior attachment zones with, in more advanced forms, dorsoventral muscles of the body wall rather than longitudinal muscles fastening to the former. Importance was placed on the mutual stabilization of constituent parts of the posterior body region. Re-alignments of the muscle induced breaking up of the longitudinal muscle sheet of the head-foot to produce muscle tracts, best exhibited in those tectibranchs which swim; they are derived from both the columellar muscle and intrinsic body wall muscles...", "contents": "The functional anatomy of the mantle complex and columellar muscle of tectibranch molluscs (Gastropoda: Opisthobranchia), and its bearing on the evolution of opisthobranch organization. An account is given of the anatomy of a series of opisthobranch molluscs principally to assess the change in importance and functioning of the mantle cavity and columellar muscle throughout the transition from prosobranch to opisthobranch organization. Intermediate steps are represented by living tectibranchs, of which Philine and Scaphander are investigated in detail, Acteon, Bulla, Haminoea, Akera, Aglaja and Gastropteron more briefly. Though an opisthobranch, Acteon has an organization typical of a monotocardian prosobranch; the remainder show trends affecting the shell and visceral mass, mantle cavity and head-foot, which resulted finally in the production of nudibranch types. It is confirmed that the adaptations exhibited by primitive tectibranchs relate to the assumption of a burrowing mode of life. Initial changes were the reduction of the nuchal area and sealing of the mantle cavity anteriorly so that it opened on the right, where it became restricted, the first perhaps prompting the sealing. A broadening and an anterior elongation of the head-foot produced a wedge to facilitate burrowing. Change in disposition of the mantle edge, incurred by differential growth, produced an involute shell with a large body whorl, alignment changing from erect to horizontal. The resultant streamlining eased infaunal progression; no vertical insinking of the viscera was involved. Subsequently the shell became reduced and finally lost. A section of the mantle edge enlarged to produce a posterior mantle lobe upon which sit both the shell and viscera, and which later became redundant as posterior elongation of the head-foot produced a slug-like form, the viscera being incorporated within the head-foot. As the nuchal area became reduced, mechanical needs prompted alteration to both the form and attachment of the columellar muscle. In Acteon the muscle is like that of a prosobranch, but the proximal region has broadened, a change of proportion required by primitive tectibranchs in order to support the floor of the mantle cavity formed from the section of mantle skirt which in prosobranchs lies on the right. This was followed by reduction and re-alignment of the entire muscle along an anteroposterior axis as emphasis changed from the muscle effecting retraction into a shell to producing contorsions of the head-foot. The shell, similarly reduced, instead of providing anchorage, became itself anchored by additional anterior and posterior attachment zones with, in more advanced forms, dorsoventral muscles of the body wall rather than longitudinal muscles fastening to the former. Importance was placed on the mutual stabilization of constituent parts of the posterior body region. Re-alignments of the muscle induced breaking up of the longitudinal muscle sheet of the head-foot to produce muscle tracts, best exhibited in those tectibranchs which swim; they are derived from both the columellar muscle and intrinsic body wall muscles..."}
{"id": "PMID:15294", "title": "[Electrolyte-water balance and acid-base equilibrium in brain tumor patients].", "content": "Electrolyte variations, water-balance disturbances, and acid-base equilibrium disorders observed in patients with brain tumors are due, in the majority of cases, to increases in intracranial pressure and, in a relatively small number of cases, to the particular location of the tumor. Severe pathological pictures are not, in general, observed until the ailment has advanced to a critical state. The authors, after describing the clinical pictures of the various forms of acid-base equilibrium disorders, also discuss methods of treatment. Disturbances of water balance are closely associated with the electrolyte metabolism. Consequently, it is necessary that, if a dehydrating form of therapy is used, careful attention should be given to the corresponding parameters. Disturbances of iatrogenic origin tend to produce particularly adverse effects in brain tumor patients.", "contents": "[Electrolyte-water balance and acid-base equilibrium in brain tumor patients]. Electrolyte variations, water-balance disturbances, and acid-base equilibrium disorders observed in patients with brain tumors are due, in the majority of cases, to increases in intracranial pressure and, in a relatively small number of cases, to the particular location of the tumor. Severe pathological pictures are not, in general, observed until the ailment has advanced to a critical state. The authors, after describing the clinical pictures of the various forms of acid-base equilibrium disorders, also discuss methods of treatment. Disturbances of water balance are closely associated with the electrolyte metabolism. Consequently, it is necessary that, if a dehydrating form of therapy is used, careful attention should be given to the corresponding parameters. Disturbances of iatrogenic origin tend to produce particularly adverse effects in brain tumor patients."}
{"id": "PMID:15295", "title": "Medazepam and the driving ability of anxious patients.", "content": "A double-blind crossover trial of Medazepam was carried out in 14 anxious hospital patients. The mean self-adjusted dosage was 16.5 mg daily. The active drug was no more effective than placebo in relieving anxiety, which was rated both clinically and by the Middlesex Health Questionnaire (M.H.Q.) (Crown and Crisp, 1970). This may have been because the dose was relatively low for chronically anxious hospital patients. Even this dosage caused significantly higher scores on the M.H.Q. scale for depression. Braking and driving simulator tests were not adversely affected by Medazepam. In real driving conditions those taking the drug made significantly more technical, but not dangerous, errors. Pulse and blood pressure also were not affected.", "contents": "Medazepam and the driving ability of anxious patients. A double-blind crossover trial of Medazepam was carried out in 14 anxious hospital patients. The mean self-adjusted dosage was 16.5 mg daily. The active drug was no more effective than placebo in relieving anxiety, which was rated both clinically and by the Middlesex Health Questionnaire (M.H.Q.) (Crown and Crisp, 1970). This may have been because the dose was relatively low for chronically anxious hospital patients. Even this dosage caused significantly higher scores on the M.H.Q. scale for depression. Braking and driving simulator tests were not adversely affected by Medazepam. In real driving conditions those taking the drug made significantly more technical, but not dangerous, errors. Pulse and blood pressure also were not affected."}
{"id": "PMID:15296", "title": "Effects of oxazolam, cloxazolam, and CS-386, new anti-anxiety drugs, on socially induced suppression and aggression in pairs of monkeys.", "content": "This experiment was conducted to examine effects of oxazolam, cloxazolam, CS-386, and reference drugs on socially induced suppression and aggression in pairs of monkeys. Oxazolam, cloxazolam, and CS-386, as well as other benzodiazepines, at both ataxic and non-ataxic doses, attenuated the socially induced suppression, but failed to show inhibitory effect on the on the socially induced aggression. Chlorpromazine, at both slight-sedative and non-sedative doses, reduced neither socially induced suppression nor aggression. Imipramine did not produce any significant effect in this study.", "contents": "Effects of oxazolam, cloxazolam, and CS-386, new anti-anxiety drugs, on socially induced suppression and aggression in pairs of monkeys. This experiment was conducted to examine effects of oxazolam, cloxazolam, CS-386, and reference drugs on socially induced suppression and aggression in pairs of monkeys. Oxazolam, cloxazolam, and CS-386, as well as other benzodiazepines, at both ataxic and non-ataxic doses, attenuated the socially induced suppression, but failed to show inhibitory effect on the on the socially induced aggression. Chlorpromazine, at both slight-sedative and non-sedative doses, reduced neither socially induced suppression nor aggression. Imipramine did not produce any significant effect in this study."}
{"id": "PMID:15297", "title": "Intensive design in evaluating anxiolytic agents.", "content": "The purposes of this study were: (1) to test the usefulness of intensive design in detecting the effects of an established antianxiety agent in a single patient studied for a period as brief as 8 weeks and (2) to explore the usefulness of combining intensive and extensive designs by jointly analyzing the results from several similarly treated patients. Fifteen primarily anxious, psychoneurotic patients aged 21-50 and scoring 17 or more on the Taylor Manifest Anxiety Scale were admitted to the study; and 11 completed the full treatment program. Medications were diazepam 5 mg t.i.d. and a matching placebo, administered under double-blind conditions. Patients were treated for 8 weeks, divided into 42-week blocks. In each block, the patient received diazepam 1 week and placebo the other, with the order in each block determined at random. The patient came weekly for evaluation, including, self-ratings on the Hopkins Symptom Checklist (SCL), global status, global change; reports of occupational and social function; resting pulse; reaction time; psychiatrist's ratings on the Hamilton Anxiety Scale, global status and global change. The patient also reported daily his mood on the Profile of Mood States (POMS). Mean deviations from the general trend for post-diazepam and postplacebo scores on each criterion were compared within patients. Diazepam-placebo differences on each criterion were analyzed between patients. Criteria that clearly recorded the anti-anxiety effect of diazepam as compared to placebo included the Hamilton Anxiety Scale, the psychiatrist's global status and global change ratings, the SCL Anxiety and Somatization Scales, and the POMS Anxiety Scale. Other criteria that showed a reliable diazepam effect included SCL Depression (decrease), POMS Vigor (increase), POMS Fatigue (decrease), SCL Anger (increase), and reaction time (increase). The most sensitive criteria distinguished diazepam from placebo even when results were considered only from the first 6 patients during their first 4 weeks of treatment- a total of 24 patient weeks of treatment. The factors contributing to the sensitivity of this design were investigated and discussed.", "contents": "Intensive design in evaluating anxiolytic agents. The purposes of this study were: (1) to test the usefulness of intensive design in detecting the effects of an established antianxiety agent in a single patient studied for a period as brief as 8 weeks and (2) to explore the usefulness of combining intensive and extensive designs by jointly analyzing the results from several similarly treated patients. Fifteen primarily anxious, psychoneurotic patients aged 21-50 and scoring 17 or more on the Taylor Manifest Anxiety Scale were admitted to the study; and 11 completed the full treatment program. Medications were diazepam 5 mg t.i.d. and a matching placebo, administered under double-blind conditions. Patients were treated for 8 weeks, divided into 42-week blocks. In each block, the patient received diazepam 1 week and placebo the other, with the order in each block determined at random. The patient came weekly for evaluation, including, self-ratings on the Hopkins Symptom Checklist (SCL), global status, global change; reports of occupational and social function; resting pulse; reaction time; psychiatrist's ratings on the Hamilton Anxiety Scale, global status and global change. The patient also reported daily his mood on the Profile of Mood States (POMS). Mean deviations from the general trend for post-diazepam and postplacebo scores on each criterion were compared within patients. Diazepam-placebo differences on each criterion were analyzed between patients. Criteria that clearly recorded the anti-anxiety effect of diazepam as compared to placebo included the Hamilton Anxiety Scale, the psychiatrist's global status and global change ratings, the SCL Anxiety and Somatization Scales, and the POMS Anxiety Scale. Other criteria that showed a reliable diazepam effect included SCL Depression (decrease), POMS Vigor (increase), POMS Fatigue (decrease), SCL Anger (increase), and reaction time (increase). The most sensitive criteria distinguished diazepam from placebo even when results were considered only from the first 6 patients during their first 4 weeks of treatment- a total of 24 patient weeks of treatment. The factors contributing to the sensitivity of this design were investigated and discussed."}
{"id": "PMID:15299", "title": "Spectrum of angiographically demonstrable renal pathology in young hypertensive patients.", "content": "The renal diseases which cause systemic hypertension in the first two decades of life differ from the adult in their incidence and etiology. Seventeen patients (11 days to 20 years old), studied angiographically, demonstrated a wide spectrum of renal pathology including arterial thrombosis, fibromuscular hyperplasia, vasculitis, neurofibramatosis, cystic disease, pyelonephritis, Page kidney, and congenital anomalies.", "contents": "Spectrum of angiographically demonstrable renal pathology in young hypertensive patients. The renal diseases which cause systemic hypertension in the first two decades of life differ from the adult in their incidence and etiology. Seventeen patients (11 days to 20 years old), studied angiographically, demonstrated a wide spectrum of renal pathology including arterial thrombosis, fibromuscular hyperplasia, vasculitis, neurofibramatosis, cystic disease, pyelonephritis, Page kidney, and congenital anomalies."}
{"id": "PMID:15300", "title": "The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro.", "content": "Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid.", "contents": "The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro. Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid."}
{"id": "PMID:15301", "title": "Evidence against the release of prostaglandin-like material from isolated intestinal tissue by pure cholera toxin.", "content": "Prostaglandin-like material was released from finely cut guinea-pig ileum or human intestinal mucosa during incubation with Krebs solution. The tissue inactivated some significant change in release of prostaglandin-like material when pure cholera toxin was incubated with guinea-pig ileum or human intestinal mucosa. The work is discussed in relation to the action of cholera toxin in vivo.", "contents": "Evidence against the release of prostaglandin-like material from isolated intestinal tissue by pure cholera toxin. Prostaglandin-like material was released from finely cut guinea-pig ileum or human intestinal mucosa during incubation with Krebs solution. The tissue inactivated some significant change in release of prostaglandin-like material when pure cholera toxin was incubated with guinea-pig ileum or human intestinal mucosa. The work is discussed in relation to the action of cholera toxin in vivo."}
{"id": "PMID:15302", "title": "Multiple molecular forms of prostaglandin 15-hydroxydehydrogenase and 9-ketoreductase in chicken kidney.", "content": "Prostaglandin-15-hydroxydehydrogenase and prostaglandin-9-keto-reductase were purified from chicken kidney. Both enzymes exist in multiple forms as determined by isoelectric focusing. The dehydrogenases catalyze the transformation of the functional group at C-15 but not the functional group at C-9. The preferred cofactors in these reactions are NAD+ or NADH. The 9-ketoreductases catalyze the reversible transformation of the functional group at C-9 and also the oxidation or reduction of the C-15 functional group. The preferred cofactors are NADP+ or NADPH. Bradykinin does not affect the activities of any of the three prostaglandin 9-ketoreductases. Flavin mononucleotide and the flavonoid, quercetin, as well as indomethacin, ethacrynic acid, and furosemide, inhibit all three 9-ketoreductases. An inhibitor of 9-ketoreductase isolated from chicken breast muscle also inhibits the three separable reductases, but the pattern of inhibition of the reductase that focuses at pH 5.7 differs from that of the reductases focusing at pH 7.8 and 8.2.", "contents": "Multiple molecular forms of prostaglandin 15-hydroxydehydrogenase and 9-ketoreductase in chicken kidney. Prostaglandin-15-hydroxydehydrogenase and prostaglandin-9-keto-reductase were purified from chicken kidney. Both enzymes exist in multiple forms as determined by isoelectric focusing. The dehydrogenases catalyze the transformation of the functional group at C-15 but not the functional group at C-9. The preferred cofactors in these reactions are NAD+ or NADH. The 9-ketoreductases catalyze the reversible transformation of the functional group at C-9 and also the oxidation or reduction of the C-15 functional group. The preferred cofactors are NADP+ or NADPH. Bradykinin does not affect the activities of any of the three prostaglandin 9-ketoreductases. Flavin mononucleotide and the flavonoid, quercetin, as well as indomethacin, ethacrynic acid, and furosemide, inhibit all three 9-ketoreductases. An inhibitor of 9-ketoreductase isolated from chicken breast muscle also inhibits the three separable reductases, but the pattern of inhibition of the reductase that focuses at pH 5.7 differs from that of the reductases focusing at pH 7.8 and 8.2."}
{"id": "PMID:15304", "title": "Studies on membrane receptor sites for serotonin in the brain.", "content": "The competitive effect of 5,6-dihydroxytryptamine, morphine and chlorpromazine on the binding of serotonin (5-HT) to rat brain slices was investigated. Ths busynaptosomal localization of the binding of morphine in bovine midbrain preparations was compared to that of 5-HT and found to be considerably higher. The condensation of 5-HT and tryptamine receptor carbonyl groups in brain with phenylisopropylhydrazine was shown in vitro and vivo. Membrane particles labeled with [14C] tryptamine or 5-HT in presence or absence of sodium borohydride (NaBH4) were extracted with chloroform-methanol (C-M) 2:1. The labeled proteolipid precipitated by ether from these extracts showed on electropherograms one single radioautographic spot which was more intense with samples treated with sodium borohydride. In column chromatography, the bound radioactivity peak eluted with the gel void volume, was associated with a protein peak. The eluted, lyophilized material of this fraction was extracted by chloroform methanol (2:1) thus suggesting its proteo-lipid nature.", "contents": "Studies on membrane receptor sites for serotonin in the brain. The competitive effect of 5,6-dihydroxytryptamine, morphine and chlorpromazine on the binding of serotonin (5-HT) to rat brain slices was investigated. Ths busynaptosomal localization of the binding of morphine in bovine midbrain preparations was compared to that of 5-HT and found to be considerably higher. The condensation of 5-HT and tryptamine receptor carbonyl groups in brain with phenylisopropylhydrazine was shown in vitro and vivo. Membrane particles labeled with [14C] tryptamine or 5-HT in presence or absence of sodium borohydride (NaBH4) were extracted with chloroform-methanol (C-M) 2:1. The labeled proteolipid precipitated by ether from these extracts showed on electropherograms one single radioautographic spot which was more intense with samples treated with sodium borohydride. In column chromatography, the bound radioactivity peak eluted with the gel void volume, was associated with a protein peak. The eluted, lyophilized material of this fraction was extracted by chloroform methanol (2:1) thus suggesting its proteo-lipid nature."}
{"id": "PMID:15305", "title": "Action of glucagon and aspirin on ionic flux, mucosal blood flow and bleeding in the fundic pouch of dogs.", "content": "Into vagally denervated (Heidenhain) pouches of 4 dogs 25 ml of 0.1 M HCl was instilled and removed at 30 min intervals for 6 hours. During the 4th, 5th, and 6th 30 min periods the acid instillate contained 5 mg/ml of aspirin. Aspirin significantly increased gastric-mucosal clearance of aminopyrine (mucosal blood flow), outputs of Na+, Ca++, Mg++, hemoglobin, and plasma transferrin-Cr51 into the pouch contents, and disappearance of H+ from lumen to mucosa. Glucagon, 50 mug/kg subcutaneously was given during irrigation with aspirin and again 1 hour later. Glucagon did not significantly affect loss of acid from lumen to mucosa or the increase in Na+, K+, Ca++, and Mg++ effluxes caused by aspirin. Glucagon significantly decreased mucosal blood flow and the hemorrhage and loss of plasma protein into the instillate induced by aspirin.", "contents": "Action of glucagon and aspirin on ionic flux, mucosal blood flow and bleeding in the fundic pouch of dogs. Into vagally denervated (Heidenhain) pouches of 4 dogs 25 ml of 0.1 M HCl was instilled and removed at 30 min intervals for 6 hours. During the 4th, 5th, and 6th 30 min periods the acid instillate contained 5 mg/ml of aspirin. Aspirin significantly increased gastric-mucosal clearance of aminopyrine (mucosal blood flow), outputs of Na+, Ca++, Mg++, hemoglobin, and plasma transferrin-Cr51 into the pouch contents, and disappearance of H+ from lumen to mucosa. Glucagon, 50 mug/kg subcutaneously was given during irrigation with aspirin and again 1 hour later. Glucagon did not significantly affect loss of acid from lumen to mucosa or the increase in Na+, K+, Ca++, and Mg++ effluxes caused by aspirin. Glucagon significantly decreased mucosal blood flow and the hemorrhage and loss of plasma protein into the instillate induced by aspirin."}
{"id": "PMID:15306", "title": "The Wien effect in compensated metabolic acidosis.", "content": "CSF and blood acid-base values were measured in compensated metabolic acidosis, induced in anesthetized dogs by infusion of dilute HCl during hyperventilation. We observed cerebral blood flow-related steady-state differences in PCO2 between CSF and arterial venous blood from the brain. The steady-state values of CSF-blood PCO2 differences and blood H+ activity were intermediate to those observed by us previously during uncompensated acidosis and alkalosis (J. Appl. Physiol. 34: 249-254, 1973). These results are consistent with predictions of the \"charged membrane hypothesis\" proposed by us to explain CSF and blood acid-base relationship during uncompensated acid-base derangements (J. Appl. Physiol. 34: 243-248, 1973).", "contents": "The Wien effect in compensated metabolic acidosis. CSF and blood acid-base values were measured in compensated metabolic acidosis, induced in anesthetized dogs by infusion of dilute HCl during hyperventilation. We observed cerebral blood flow-related steady-state differences in PCO2 between CSF and arterial venous blood from the brain. The steady-state values of CSF-blood PCO2 differences and blood H+ activity were intermediate to those observed by us previously during uncompensated acidosis and alkalosis (J. Appl. Physiol. 34: 249-254, 1973). These results are consistent with predictions of the \"charged membrane hypothesis\" proposed by us to explain CSF and blood acid-base relationship during uncompensated acid-base derangements (J. Appl. Physiol. 34: 243-248, 1973)."}
{"id": "PMID:15303", "title": "[An unusual case of small intestine infarction of venous origin].", "content": "The evolution is presented, of a partial infarction of the small bowel, of venous origin, without apparent cause. In the 10-th day after onset, following a segmentary resection of the jejunum and termino-terminal anastomosis, the patient had another segmentar infarction of the ileon, also of venous origin, that was cured after resection. After recovery the hematological investigations evidenced a coagulation disturbance that necessitated longterm heparin therapy, a treatment that is continued 3 years after surgery. Although the repeated infarction of the small bowel of venous origin is theoretically possible the case presented appears to be unique by its evolution and the result of the medico-surgical treatment.", "contents": "[An unusual case of small intestine infarction of venous origin]. The evolution is presented, of a partial infarction of the small bowel, of venous origin, without apparent cause. In the 10-th day after onset, following a segmentary resection of the jejunum and termino-terminal anastomosis, the patient had another segmentar infarction of the ileon, also of venous origin, that was cured after resection. After recovery the hematological investigations evidenced a coagulation disturbance that necessitated longterm heparin therapy, a treatment that is continued 3 years after surgery. Although the repeated infarction of the small bowel of venous origin is theoretically possible the case presented appears to be unique by its evolution and the result of the medico-surgical treatment."}
{"id": "PMID:15307", "title": "Postnatal changes in blood respiratory characteristics in an American opossum (Didelphis virginiana).", "content": "The oxygen affinity of opossum blood changes in the postnatal period. The youngest opossums studied were 53 days of age (dated from the day of transit from vagina to pouch) and still confined to the maternal pouch: they had a blood P50 of 32.6 +/- 2.9 mm Hg. The blood P50 value then increased significantly, in two steps. First, while the young were still in the pouch, blood P50 rose secondary to a rise in the concentration of 2,3-diphosphoglycerate (DPG). Blood P50 and DPG concentration then remained stable until the animals left the maternal pouch, when DPG rose again, causing a further increment in the blood P50 which peaked at 48.7 +/- 4.5 mm Hg in animals 148 days old. Blood P50 subsequently decreased significantly, reaching the adult value (42.0 +/- 1.9 mm Hg) at about 250 days.", "contents": "Postnatal changes in blood respiratory characteristics in an American opossum (Didelphis virginiana). The oxygen affinity of opossum blood changes in the postnatal period. The youngest opossums studied were 53 days of age (dated from the day of transit from vagina to pouch) and still confined to the maternal pouch: they had a blood P50 of 32.6 +/- 2.9 mm Hg. The blood P50 value then increased significantly, in two steps. First, while the young were still in the pouch, blood P50 rose secondary to a rise in the concentration of 2,3-diphosphoglycerate (DPG). Blood P50 and DPG concentration then remained stable until the animals left the maternal pouch, when DPG rose again, causing a further increment in the blood P50 which peaked at 48.7 +/- 4.5 mm Hg in animals 148 days old. Blood P50 subsequently decreased significantly, reaching the adult value (42.0 +/- 1.9 mm Hg) at about 250 days."}
{"id": "PMID:15309", "title": "Hemoglobin function in stored blood, XVII. Maintenance of red cell 2,3 DPG (function) and ATP (viability) for six weeks in ACD or CPD-adenine-inosine-methylene blue.", "content": "Blood preservatives containing adenine for six week storage have been prepared with inosine and methylene blue at various pH levels in order to maintain, 23-DPG levels for immediate oxygen transport upon transfusion. In one experiment, the adverse effect of a high pH on ATP maintenance was demonstrated in the presence of methylene blue and inosine. In this and other experiments  it was clear that ATP was better maintained in low pH preservatives and DPG better maintained in higher pH preservatives. However, 2,3-DPG levels were kept from falling with CPD-adenine-inosine over a wide range of pH values. A CPD-adenine-inosine preservative at a pH 5.8 maintained normal DPG levels for three weeks of storage. A similar preservative but with a pH of 6.6 maintained normal DPG levels for 35 days of storage. It is suggested that if all blood bank units are going to have normal DPG levels for optimal oxygen transport at the time of transfusion then a CPD preservative with a higher pH and/or metabolic nutrients and regulators such as inosine or methylene blue would be required.", "contents": "Hemoglobin function in stored blood, XVII. Maintenance of red cell 2,3 DPG (function) and ATP (viability) for six weeks in ACD or CPD-adenine-inosine-methylene blue. Blood preservatives containing adenine for six week storage have been prepared with inosine and methylene blue at various pH levels in order to maintain, 23-DPG levels for immediate oxygen transport upon transfusion. In one experiment, the adverse effect of a high pH on ATP maintenance was demonstrated in the presence of methylene blue and inosine. In this and other experiments  it was clear that ATP was better maintained in low pH preservatives and DPG better maintained in higher pH preservatives. However, 2,3-DPG levels were kept from falling with CPD-adenine-inosine over a wide range of pH values. A CPD-adenine-inosine preservative at a pH 5.8 maintained normal DPG levels for three weeks of storage. A similar preservative but with a pH of 6.6 maintained normal DPG levels for 35 days of storage. It is suggested that if all blood bank units are going to have normal DPG levels for optimal oxygen transport at the time of transfusion then a CPD preservative with a higher pH and/or metabolic nutrients and regulators such as inosine or methylene blue would be required."}
{"id": "PMID:15311", "title": "The effect of intragastric pH-variations on the gastric acid response to insulin hypoglycaemia in healthy subjects and duodenal ulcer patients.", "content": "The gastric acid response to i.v. injection of 0.15 U of soluble insulin/kg b.w. was determined in healthy subjects and duodenal ulcer patients during intragastric perfusion with water, 0.1 M HC1, and alkaline buffer (pH 8.3). Perfusion with hydrochloric acid significantly reduced the peak gastric acid output following insulin in 6 healthy subjects (reduction 45%, p less than 0.05) but had no significant effect on the peak gastric acid response to insulin in 7 DU patients (reduction 16%, p greater than 0.05). The 2.5-hour gastric acid response to insulin was, however, significantly reduced in both groups (56% and 35%, respectively) by exogenous acidification of the stomach. The gastric acid response to insulin hypoglycaemia in 3 DU patients was the same with intragastric water and alkaline buffer perfusion. The reduction of the gastric acid response to insulin hypoglycaemia by intragastric acidification corresponded to a reduced volume secretion and could not be ascribed to increased back diffusion of hydrogen ions or duodenal inhibition. These findings suggest that the gastric acid response to insulin hypoglycaemia is inhibited by a low intragastric pH in man, and that DU patients are less sensitive to the inhibitory mechanism than healthy subjects.", "contents": "The effect of intragastric pH-variations on the gastric acid response to insulin hypoglycaemia in healthy subjects and duodenal ulcer patients. The gastric acid response to i.v. injection of 0.15 U of soluble insulin/kg b.w. was determined in healthy subjects and duodenal ulcer patients during intragastric perfusion with water, 0.1 M HC1, and alkaline buffer (pH 8.3). Perfusion with hydrochloric acid significantly reduced the peak gastric acid output following insulin in 6 healthy subjects (reduction 45%, p less than 0.05) but had no significant effect on the peak gastric acid response to insulin in 7 DU patients (reduction 16%, p greater than 0.05). The 2.5-hour gastric acid response to insulin was, however, significantly reduced in both groups (56% and 35%, respectively) by exogenous acidification of the stomach. The gastric acid response to insulin hypoglycaemia in 3 DU patients was the same with intragastric water and alkaline buffer perfusion. The reduction of the gastric acid response to insulin hypoglycaemia by intragastric acidification corresponded to a reduced volume secretion and could not be ascribed to increased back diffusion of hydrogen ions or duodenal inhibition. These findings suggest that the gastric acid response to insulin hypoglycaemia is inhibited by a low intragastric pH in man, and that DU patients are less sensitive to the inhibitory mechanism than healthy subjects."}
{"id": "PMID:15312", "title": "Pancreatic extract and the intestinal uptake of vitamin B12. III. Stimulatory effect in the presence of a non-intrinsic factor vitamin B12 binder.", "content": "To determine the mechanism by which pancreatic extract (PE) corrects the malabsorption of vitamin B12 in chronic pancreatic insufficiency (CPI), the following hypotheses were investigated: Firstly, PE might stimulate the absorption of vitamin B12 by changing the intestinal pH, secondly PE might stimulate the intestinal uptake of unbound vitamin B12, thirdly PE might abolish the inhibitory effect of vitamin B12 binders on the intestinal uptake of vitamin B12 bound to intrinsic factor (IF). PE had no effect on the pH in the small intestine and did not stimulate the uptake of unbound 57CoB12 by perfused rat intestinal segments. Preincubation of 57CoB12-IF with a non-IF B12-binder from human saliva (R-binder) reduced the uptake of 57CoB12 from 18.5 pg per cm intestine +/- 3.4 S.E.M. to 7.8 +/- 1.6 (p less than 0.02). PE abolished this inhibitory effect (p less than 0.05). The results indicate that PE corrects the malabsorption of vitamin B12 in CPI by an effect on non-IF B12- binders.", "contents": "Pancreatic extract and the intestinal uptake of vitamin B12. III. Stimulatory effect in the presence of a non-intrinsic factor vitamin B12 binder. To determine the mechanism by which pancreatic extract (PE) corrects the malabsorption of vitamin B12 in chronic pancreatic insufficiency (CPI), the following hypotheses were investigated: Firstly, PE might stimulate the absorption of vitamin B12 by changing the intestinal pH, secondly PE might stimulate the intestinal uptake of unbound vitamin B12, thirdly PE might abolish the inhibitory effect of vitamin B12 binders on the intestinal uptake of vitamin B12 bound to intrinsic factor (IF). PE had no effect on the pH in the small intestine and did not stimulate the uptake of unbound 57CoB12 by perfused rat intestinal segments. Preincubation of 57CoB12-IF with a non-IF B12-binder from human saliva (R-binder) reduced the uptake of 57CoB12 from 18.5 pg per cm intestine +/- 3.4 S.E.M. to 7.8 +/- 1.6 (p less than 0.02). PE abolished this inhibitory effect (p less than 0.05). The results indicate that PE corrects the malabsorption of vitamin B12 in CPI by an effect on non-IF B12- binders."}
{"id": "PMID:15313", "title": "Effect of changes in the intragastric milieu on competence of the gastro-oesophageal region. A study in normal subjects.", "content": "Acid-reflux studies were carried out in 10 healthy subjects in the basal state, during continuous infusion of pentagastrin (0.015 mug/kg body-weight) after bolus injection of insulin (0.2 IU/kg bodyweight), and after intragastric instillation of 200 ml hydrochloric acid. Basal gastro-oesophageal sphincter pressure and rise in intragastric pressure on leg raising were measured by means of perfused catheters. The increase of intragastric acidity during infusion of pentagastrin and during insulin-induced hypoglycaemia was not accompanied by changes in the competence of the gastro-oesophageal region. Instillation of hydrochloric acid was followed by a significant enhancement of the reflux tendency. Changes in intragastric pressure-rise were not demonstrated in any of the series of investigation. Gastric acid secretion and its significance at the evaluation of the results of reflux studies by means of pH-measuring equipment has not been clarified in patients. It can therefore reasonably be demanded of future acid reflux studies that details have to be stated with regard to acid secretion, and that these should be taken into account at the assessment of the results of the study.", "contents": "Effect of changes in the intragastric milieu on competence of the gastro-oesophageal region. A study in normal subjects. Acid-reflux studies were carried out in 10 healthy subjects in the basal state, during continuous infusion of pentagastrin (0.015 mug/kg body-weight) after bolus injection of insulin (0.2 IU/kg bodyweight), and after intragastric instillation of 200 ml hydrochloric acid. Basal gastro-oesophageal sphincter pressure and rise in intragastric pressure on leg raising were measured by means of perfused catheters. The increase of intragastric acidity during infusion of pentagastrin and during insulin-induced hypoglycaemia was not accompanied by changes in the competence of the gastro-oesophageal region. Instillation of hydrochloric acid was followed by a significant enhancement of the reflux tendency. Changes in intragastric pressure-rise were not demonstrated in any of the series of investigation. Gastric acid secretion and its significance at the evaluation of the results of reflux studies by means of pH-measuring equipment has not been clarified in patients. It can therefore reasonably be demanded of future acid reflux studies that details have to be stated with regard to acid secretion, and that these should be taken into account at the assessment of the results of the study."}
{"id": "PMID:15314", "title": "Continuous oesophageal pH recording and acid-clearing test. A study of reproducibility.", "content": "Ten investigations of acid reflux by means of 12-hour continuous pH monitoring at the distal end of the oesophagus, and 10 acid-clearing tests were performed within 6 weeks on the same volunteer with the purpose of examining the reproducibility of the results of these tests. Intragastric pH was studied over 12 hours and proved to be under 3 during the whole period of investigation. For the acid reflux test the coefficient of variation was 0.61-0.94, depending on the criteria for reflux. For the acid-clearing test the coefficient of variation was 0.22. For both tests the results of the separate investigations varied within normal ranges.", "contents": "Continuous oesophageal pH recording and acid-clearing test. A study of reproducibility. Ten investigations of acid reflux by means of 12-hour continuous pH monitoring at the distal end of the oesophagus, and 10 acid-clearing tests were performed within 6 weeks on the same volunteer with the purpose of examining the reproducibility of the results of these tests. Intragastric pH was studied over 12 hours and proved to be under 3 during the whole period of investigation. For the acid reflux test the coefficient of variation was 0.61-0.94, depending on the criteria for reflux. For the acid-clearing test the coefficient of variation was 0.22. For both tests the results of the separate investigations varied within normal ranges."}
{"id": "PMID:15315", "title": "Theta-bearing cells in the bone marrow of thymus-deprived mice. Numbers and nature.", "content": "Theta-bearing cells in lymphomyeloid tissues of thymus-deprived and normal mice have been studied by the use of anti-theta antiserum and cytotoxicity tests in addition to functional tests. In contrast to the findings in peripheral lymphoid tissues, increased percentages and numbers of theta-bearing cells were found in the bone marrow of neonatally and nude mice as compared with normal and sham-thymectomized mice. In adult thymectomized mice, percentages comparable to those in sham-operated littermates were found. The findings were not due to irrelevant antibodies in the anti-theta antiserum, and neonatally thymectomized mice grafted with a thymic lobe showed percentages of theta-positive cells in the bone marrow comparable to those of sham-operated animals. Adrenalectomy did not lead to diminished percentages of theta-positive cells in the bone marrow of neonatally thymectomized mice, and the serum levels of hydrocortisone and corticosterone were within normal ranges in thymus-deprived mice. The mitogen responses and graft-versus-host activity of bone marrow cells from neonatally thymectomized mice suggest that most theta-positive cells in the bone marrow of these mice are functionally immature cells.", "contents": "Theta-bearing cells in the bone marrow of thymus-deprived mice. Numbers and nature. Theta-bearing cells in lymphomyeloid tissues of thymus-deprived and normal mice have been studied by the use of anti-theta antiserum and cytotoxicity tests in addition to functional tests. In contrast to the findings in peripheral lymphoid tissues, increased percentages and numbers of theta-bearing cells were found in the bone marrow of neonatally and nude mice as compared with normal and sham-thymectomized mice. In adult thymectomized mice, percentages comparable to those in sham-operated littermates were found. The findings were not due to irrelevant antibodies in the anti-theta antiserum, and neonatally thymectomized mice grafted with a thymic lobe showed percentages of theta-positive cells in the bone marrow comparable to those of sham-operated animals. Adrenalectomy did not lead to diminished percentages of theta-positive cells in the bone marrow of neonatally thymectomized mice, and the serum levels of hydrocortisone and corticosterone were within normal ranges in thymus-deprived mice. The mitogen responses and graft-versus-host activity of bone marrow cells from neonatally thymectomized mice suggest that most theta-positive cells in the bone marrow of these mice are functionally immature cells."}
{"id": "PMID:15317", "title": "Tris buffer attenuates acetylcholine responses in Aplysia neurons.", "content": "The commonly used buffering agent tris(hydroxymethyl)methylamine (tris) antagonizes the action of iontophoretically applied acetylcholine on neurons of Aplysia californica. Concentrations of 5 to 10 millimolar tris markedly reduced both excitatory and inhibitory responses.", "contents": "Tris buffer attenuates acetylcholine responses in Aplysia neurons. The commonly used buffering agent tris(hydroxymethyl)methylamine (tris) antagonizes the action of iontophoretically applied acetylcholine on neurons of Aplysia californica. Concentrations of 5 to 10 millimolar tris markedly reduced both excitatory and inhibitory responses."}
{"id": "PMID:15320", "title": "Injuries from sea urchins.", "content": "Injuries from sea urchins result from penetration of the calcareous spines into the skin. Local pain of several days' duration is the most common symptom, but systemic reaction from toxins found in certain species can occur. There is no uniformly accepted successful treatment other than cleansing the wound. Attempts to remove the imbedded spines can increase the severity of the reaction.", "contents": "Injuries from sea urchins. Injuries from sea urchins result from penetration of the calcareous spines into the skin. Local pain of several days' duration is the most common symptom, but systemic reaction from toxins found in certain species can occur. There is no uniformly accepted successful treatment other than cleansing the wound. Attempts to remove the imbedded spines can increase the severity of the reaction."}
{"id": "PMID:15322", "title": "The effect of a sodium citrate preparation compared with an aluminium-magnesium hydroxide preparation on the urinary pH of normal subjects.", "content": "The effects of a sodium citrate preparation in two dosage regimens (4 g 4 times daily and 8 g 4 times daily) and of an aluminium-magnesium hydroxide suspension (15 ml 4 times daily) on the urinary pH of 19 healthy subjects were compared. The sodium citrate preparation in both dosages proved to be superior to the aluminium-magnesium hydroxide suspension in elevating the urinary pH. Urinary pH values as high as 8 were reached with the sodium citrate preparation. Blood pH, blood gases and electrolyte changes were within normal limits.", "contents": "The effect of a sodium citrate preparation compared with an aluminium-magnesium hydroxide preparation on the urinary pH of normal subjects. The effects of a sodium citrate preparation in two dosage regimens (4 g 4 times daily and 8 g 4 times daily) and of an aluminium-magnesium hydroxide suspension (15 ml 4 times daily) on the urinary pH of 19 healthy subjects were compared. The sodium citrate preparation in both dosages proved to be superior to the aluminium-magnesium hydroxide suspension in elevating the urinary pH. Urinary pH values as high as 8 were reached with the sodium citrate preparation. Blood pH, blood gases and electrolyte changes were within normal limits."}
{"id": "PMID:15323", "title": "Medical treatment of hypertension.", "content": "The management of hypertension with current hypotensive drugs on the South African pharmaceutical market is reviewed. The advent of the use of beta-adrenergic blocking agents and vasodilators in the treatment of hypertension is promising.", "contents": "Medical treatment of hypertension. The management of hypertension with current hypotensive drugs on the South African pharmaceutical market is reviewed. The advent of the use of beta-adrenergic blocking agents and vasodilators in the treatment of hypertension is promising."}
{"id": "PMID:15319", "title": "[Endocrine polyadenomatosis with carcinoid tumor].", "content": "The authors review 26 cases of multiple endocrine tumours with presence of a carcinoid tumour. In 44% the carcinoid was localised to the bronchus, in 20% of cases to the small intestine or duodenum. In 76% of cases during multiple endocrine tumours, the carcinoid appeared in embryological derivatives of the anterior part of the intestine. No carcinoid syndrome was reported. The difficulty of histological distinction has led to the description of carcinoid islet cell tumours. These facts fit in with the APUD concept.", "contents": "[Endocrine polyadenomatosis with carcinoid tumor]. The authors review 26 cases of multiple endocrine tumours with presence of a carcinoid tumour. In 44% the carcinoid was localised to the bronchus, in 20% of cases to the small intestine or duodenum. In 76% of cases during multiple endocrine tumours, the carcinoid appeared in embryological derivatives of the anterior part of the intestine. No carcinoid syndrome was reported. The difficulty of histological distinction has led to the description of carcinoid islet cell tumours. These facts fit in with the APUD concept."}
{"id": "PMID:15324", "title": "Clothiapine in the management of schizophrenia.", "content": "Forty Black men diagnosed as schizophrenic and admitted to Ingutsheni Hospital during a period of 3 months, were allocated alternately to treatment with either clothiapine or chlorpromazine. Six patients were excluded from the trial because of an incorrect diagnosis and 34, 17 in each group, completed the trial. The 2 groups were comparable for both severity and symptoms of their illnesses. Degrees of regression of psychotic symptoms as assessed by the Brief Psychiatric Rating Scale, were comparable for the 2 groups. Adverse effects were not troublesome with clothiapine and there was no evidence of disturbed liver function, but haemoglobin values and white cell counts were sometimes decreased. EEG studies showed that clothiapine produced an increase in the slow activity but no paroxysmal acitvity. It was concluded that clothiapine is a valuable drug for the management of actue schizophrenia.", "contents": "Clothiapine in the management of schizophrenia. Forty Black men diagnosed as schizophrenic and admitted to Ingutsheni Hospital during a period of 3 months, were allocated alternately to treatment with either clothiapine or chlorpromazine. Six patients were excluded from the trial because of an incorrect diagnosis and 34, 17 in each group, completed the trial. The 2 groups were comparable for both severity and symptoms of their illnesses. Degrees of regression of psychotic symptoms as assessed by the Brief Psychiatric Rating Scale, were comparable for the 2 groups. Adverse effects were not troublesome with clothiapine and there was no evidence of disturbed liver function, but haemoglobin values and white cell counts were sometimes decreased. EEG studies showed that clothiapine produced an increase in the slow activity but no paroxysmal acitvity. It was concluded that clothiapine is a valuable drug for the management of actue schizophrenia."}
{"id": "PMID:15325", "title": "Interpretation of alveolar-arterial oxygen tension difference.", "content": "In this study, an assessment is given of errors resulting from the use of the alveolar-arterial oxygen difference determined on both room air and 100% oxygen in estimating changes in total shunt fraction of 41 patients hospitalized with long bone fractures. In 113 studies, changes in alveolar-arterial oxygen difference in 29 patients were in the opposite direction to changes in shunt fraction. Based upon these studies, changes of less than 45 millimeters in the arterial oxygen tension determined with a patient breathing 100% oxygen are not reliable indicators of direction of change in shunt fraction. In 126 studies, the shunt fraction determined from arterial and mixed venous oxygen contents in 71 patients was greater when determined on 100% oxygen than when determined on room air, a possible indication of the induction of alveolar or small airway collapse. The errors in estimation of shunt fraction due to assuming a value for arteriovenous oxygen content difference become larger as total shunt fraction increases; in particular, use of the alveolar-arterial oxygen difference as a guide to serial changes in pulmonary dysfunction can be particularly misleading when the alveolar-arterial oxygen tension difference is so large that the arterial hemoglobin is less than fully saturated on 100% oxygen. Use of mixed venous samples was found necessary, in these instances, to avoid large errors in estimation of total shunt fraction.", "contents": "Interpretation of alveolar-arterial oxygen tension difference. In this study, an assessment is given of errors resulting from the use of the alveolar-arterial oxygen difference determined on both room air and 100% oxygen in estimating changes in total shunt fraction of 41 patients hospitalized with long bone fractures. In 113 studies, changes in alveolar-arterial oxygen difference in 29 patients were in the opposite direction to changes in shunt fraction. Based upon these studies, changes of less than 45 millimeters in the arterial oxygen tension determined with a patient breathing 100% oxygen are not reliable indicators of direction of change in shunt fraction. In 126 studies, the shunt fraction determined from arterial and mixed venous oxygen contents in 71 patients was greater when determined on 100% oxygen than when determined on room air, a possible indication of the induction of alveolar or small airway collapse. The errors in estimation of shunt fraction due to assuming a value for arteriovenous oxygen content difference become larger as total shunt fraction increases; in particular, use of the alveolar-arterial oxygen difference as a guide to serial changes in pulmonary dysfunction can be particularly misleading when the alveolar-arterial oxygen tension difference is so large that the arterial hemoglobin is less than fully saturated on 100% oxygen. Use of mixed venous samples was found necessary, in these instances, to avoid large errors in estimation of total shunt fraction."}
{"id": "PMID:15326", "title": "The effect of furosemide on the flow and composition of bile in the dog.", "content": "The effect of furosemide, a potent inhibitor of active sodium transport, on the amount and composition of bile was studied in the dog. Ten milligrams per kilogram of body weight of furosemide were injected intravenously to anesthetized dogs with a previously constructed fistula of the common bile duct. In all dogs, a 2.5 times increase in bile flow was observed concomitant with a 15 times increase in urinary output. The amount of bile flow decreased gradually and returned to control levels 60 to 75 minutes after furosemide injection. The choleretic effect was associated with a high increase in sodium, chloride and bicarbonate anions and with a smaller increase in potassium, phosphorus and calcium. The total amount of bilirubin alkaline phosphatase and cholesterol was not significantly affected, while the calculated output of inorganic salts increased. The results indicate that inhibition of sodium reabsorption by furosemide simultaneously affects the liver and kidney and that the increase in electrolyte solution is most likely caused by the inhibition of sodium reabsorption in the ductuli. Furosemide also may interfere with the sodium mediated secretory fraction at the canalicular level, but the predominant factor determining the increase in bile flow and electrolytes is inhibition of sodium reabsorption in the biliary ducts and ductuli.", "contents": "The effect of furosemide on the flow and composition of bile in the dog. The effect of furosemide, a potent inhibitor of active sodium transport, on the amount and composition of bile was studied in the dog. Ten milligrams per kilogram of body weight of furosemide were injected intravenously to anesthetized dogs with a previously constructed fistula of the common bile duct. In all dogs, a 2.5 times increase in bile flow was observed concomitant with a 15 times increase in urinary output. The amount of bile flow decreased gradually and returned to control levels 60 to 75 minutes after furosemide injection. The choleretic effect was associated with a high increase in sodium, chloride and bicarbonate anions and with a smaller increase in potassium, phosphorus and calcium. The total amount of bilirubin alkaline phosphatase and cholesterol was not significantly affected, while the calculated output of inorganic salts increased. The results indicate that inhibition of sodium reabsorption by furosemide simultaneously affects the liver and kidney and that the increase in electrolyte solution is most likely caused by the inhibition of sodium reabsorption in the ductuli. Furosemide also may interfere with the sodium mediated secretory fraction at the canalicular level, but the predominant factor determining the increase in bile flow and electrolytes is inhibition of sodium reabsorption in the biliary ducts and ductuli."}
{"id": "PMID:15327", "title": "Effect of intraduodenal acid on the pre- and postvagotomy basal gastric secretion and gastrin.", "content": "Acid instillation into the duodenum inhibits basal and stimulated gastric secretion. In man vagotomy suppresses this secretory inhibition. It is postulated that such inhibition responds to a dual mechanism: an hormonal one (enterogastrone) and a nervous one (vagus nerve). This study showed that preoperative duodenal acidification of duodenal ulcer patients results in a decrease in basal gastric secretion and in gastrin levels. On the contrary, in patients submitted to vagal denervation--either through truncal division or highly selective vagotomy--duodenal acidification does not inhibit gastric secretion; however, a drop occurs in basal gastrin levels. An intact gastric vagal innervation therefore, seems necessary for the preservation of the sensitivity of the parietal cell to the effect of hormonal inhibitors, it being immaterial whether duodenal innervation is present or not, as that duodenal acidification provokes a significant fall in serum gastrin levels as determined by radioimmunoassay. This hormonal decrease produced by duodenal acidification can be explained by the inhibition of gastrin release from the antrum. Agreement is expressed with the opinion of other authors that highly selective vagotomy does not appear to carry any advantage over truncal section of the vagus nerves from the standpoint of the inhibitory mechanism of gastric secretion from the duodenum.", "contents": "Effect of intraduodenal acid on the pre- and postvagotomy basal gastric secretion and gastrin. Acid instillation into the duodenum inhibits basal and stimulated gastric secretion. In man vagotomy suppresses this secretory inhibition. It is postulated that such inhibition responds to a dual mechanism: an hormonal one (enterogastrone) and a nervous one (vagus nerve). This study showed that preoperative duodenal acidification of duodenal ulcer patients results in a decrease in basal gastric secretion and in gastrin levels. On the contrary, in patients submitted to vagal denervation--either through truncal division or highly selective vagotomy--duodenal acidification does not inhibit gastric secretion; however, a drop occurs in basal gastrin levels. An intact gastric vagal innervation therefore, seems necessary for the preservation of the sensitivity of the parietal cell to the effect of hormonal inhibitors, it being immaterial whether duodenal innervation is present or not, as that duodenal acidification provokes a significant fall in serum gastrin levels as determined by radioimmunoassay. This hormonal decrease produced by duodenal acidification can be explained by the inhibition of gastrin release from the antrum. Agreement is expressed with the opinion of other authors that highly selective vagotomy does not appear to carry any advantage over truncal section of the vagus nerves from the standpoint of the inhibitory mechanism of gastric secretion from the duodenum."}
{"id": "PMID:15328", "title": "Relationship between the prolongation of warm ischemia and the maximum available preservation period.", "content": "Fifty dog kidneys had hypothermic perfusion for 12 to 72 hours and then were transplanted. Prior to perfusion the kidneys were subjected to 15, 30, 45, and 60 minutes of warm ischemia. Fifteen minutes of warm ischemia was well tolerated (successful 72 hour preservation), but after 30 minutes successful preservation could be achieved for 24 hours only. Enzyme release and lactate formation were related to the prolongation of warm ischemia, and the highly significant concentration differences of these substances, between well functioning kidneys and those with small or no function, indicated the viability of the organ.", "contents": "Relationship between the prolongation of warm ischemia and the maximum available preservation period. Fifty dog kidneys had hypothermic perfusion for 12 to 72 hours and then were transplanted. Prior to perfusion the kidneys were subjected to 15, 30, 45, and 60 minutes of warm ischemia. Fifteen minutes of warm ischemia was well tolerated (successful 72 hour preservation), but after 30 minutes successful preservation could be achieved for 24 hours only. Enzyme release and lactate formation were related to the prolongation of warm ischemia, and the highly significant concentration differences of these substances, between well functioning kidneys and those with small or no function, indicated the viability of the organ."}
{"id": "PMID:15329", "title": "Effect of endotoxin shock on skeletal muscle cell membrane potential.", "content": "Transmembrane potential changes were monitored in 21 dogs that were shocked by intravenous injectin of Difco purified endotoxin (055:B5). Corresponding serial measurements of electrolyte concentration in plasma and muscle biopsies were obtained to assess fluid and electrolyte changes. During shock the transmembrane potential was found to become significantly less negative (-55.2 mv.) from a control of -87.5 mv. (p less than 0.001). A significant efflux of K+ (p less than 0.02) from the cell was recorded, but intracellular Na+ and Cl- concentration rose. A plausable explanation for the fluid and electrolyte shifts, possibly due to a decrease in the muscle temperature and a resultant decline in metabolism, has been offered.", "contents": "Effect of endotoxin shock on skeletal muscle cell membrane potential. Transmembrane potential changes were monitored in 21 dogs that were shocked by intravenous injectin of Difco purified endotoxin (055:B5). Corresponding serial measurements of electrolyte concentration in plasma and muscle biopsies were obtained to assess fluid and electrolyte changes. During shock the transmembrane potential was found to become significantly less negative (-55.2 mv.) from a control of -87.5 mv. (p less than 0.001). A significant efflux of K+ (p less than 0.02) from the cell was recorded, but intracellular Na+ and Cl- concentration rose. A plausable explanation for the fluid and electrolyte shifts, possibly due to a decrease in the muscle temperature and a resultant decline in metabolism, has been offered."}
{"id": "PMID:15337", "title": "[Effect of thymus cells on the radiosensitivity and differentiation trends of hematopoietic stem cells].", "content": "A stimulating influence of thymus cells on the capability of irradiated (from 100 to 500 r) bone marrow of mice of producing colonies in spleen of syngenous recipient has been proven. The intensification of colony formation involves an increased radioresistance of stem cells. It is supposed that radioresistant thymus cells have a stimulating effect. Thymus cells exert their influence not only to the rate of survival of stem cells proliferating in the bone marrow of femur, but also increase their erythropoetic potention.", "contents": "[Effect of thymus cells on the radiosensitivity and differentiation trends of hematopoietic stem cells]. A stimulating influence of thymus cells on the capability of irradiated (from 100 to 500 r) bone marrow of mice of producing colonies in spleen of syngenous recipient has been proven. The intensification of colony formation involves an increased radioresistance of stem cells. It is supposed that radioresistant thymus cells have a stimulating effect. Thymus cells exert their influence not only to the rate of survival of stem cells proliferating in the bone marrow of femur, but also increase their erythropoetic potention."}
{"id": "PMID:15334", "title": "Local mechanism of CO2 action of cat pial arterioles.", "content": "The effect of local hypercapnic acidosis or local hypocapnic alkalosis on pial arterioles were studied in anesthetized cats equipped with a cranial window for the direct observation of the pial microcirculation of the parietal cortex. Changes in PCO2 and pH of the extracellular fluid were induced by perfusing the space under the cranial window with artificial cerebrospinal fluid equilibrated with different concentrations of CO2, while PaCO2 was maintained constant. Hypercapnic acidosis dilated and hypocapnic alkalosis constricted pial arteioles markedly. The results indicate that a basis exists for considering CO2 as a mediator for local regulation of brain blood flow. The vasodilation associated with arterial hypercapnia was abolished by a reduction in CSF PCO2 equal in magnitude to the rise in arterial blood PCO2, suggesting that the action of CO2 is entirely local.", "contents": "Local mechanism of CO2 action of cat pial arterioles. The effect of local hypercapnic acidosis or local hypocapnic alkalosis on pial arterioles were studied in anesthetized cats equipped with a cranial window for the direct observation of the pial microcirculation of the parietal cortex. Changes in PCO2 and pH of the extracellular fluid were induced by perfusing the space under the cranial window with artificial cerebrospinal fluid equilibrated with different concentrations of CO2, while PaCO2 was maintained constant. Hypercapnic acidosis dilated and hypocapnic alkalosis constricted pial arteioles markedly. The results indicate that a basis exists for considering CO2 as a mediator for local regulation of brain blood flow. The vasodilation associated with arterial hypercapnia was abolished by a reduction in CSF PCO2 equal in magnitude to the rise in arterial blood PCO2, suggesting that the action of CO2 is entirely local."}
{"id": "PMID:15335", "title": "Subclavian steal in Takayasu's arteritis. A hemodynamic study by means of ultrasonic Doppler flowmetry.", "content": "Blood flow in the vertebral artery and the upper extremity was studied in five cases of Takayasu's arteritis with subclavian steal by use of ultrasonic Doppler flowmetry and finger plethysmography. The diagnosis of subclavian steal was made by observation of flow reversal in the vertebral artery on the subclavian steal side during grip exercise and, in addition, the vertebral flow change with brachial artery occlusion. The blood flow increase of both internal cartotid and non-affected (non-subclavian steal side) vertebral arteries during a common carotid compression was almost normal in patients with Takayasu's arteritis in this study. During carotid compression on the side of the subclavian steal, ipsilateral vertebral blood flow greatly decreased, and the amplitude the ipsilateral finger plethysmogram decreased slightly or moderately. It is suggested that there are significantly important factors in suppressing sumptoms of vertebrobasilar ischemia in these patients with Takayasu's arteritis with subclavian steal. These factors are believed to be (1) good function of the circle of Willis, (2) good blood supply to the brain stem, and (3) collateral circulation to the distal subclavian artery not via the vertebral artery.", "contents": "Subclavian steal in Takayasu's arteritis. A hemodynamic study by means of ultrasonic Doppler flowmetry. Blood flow in the vertebral artery and the upper extremity was studied in five cases of Takayasu's arteritis with subclavian steal by use of ultrasonic Doppler flowmetry and finger plethysmography. The diagnosis of subclavian steal was made by observation of flow reversal in the vertebral artery on the subclavian steal side during grip exercise and, in addition, the vertebral flow change with brachial artery occlusion. The blood flow increase of both internal cartotid and non-affected (non-subclavian steal side) vertebral arteries during a common carotid compression was almost normal in patients with Takayasu's arteritis in this study. During carotid compression on the side of the subclavian steal, ipsilateral vertebral blood flow greatly decreased, and the amplitude the ipsilateral finger plethysmogram decreased slightly or moderately. It is suggested that there are significantly important factors in suppressing sumptoms of vertebrobasilar ischemia in these patients with Takayasu's arteritis with subclavian steal. These factors are believed to be (1) good function of the circle of Willis, (2) good blood supply to the brain stem, and (3) collateral circulation to the distal subclavian artery not via the vertebral artery."}
{"id": "PMID:15336", "title": "Changes in agglomeration of human red blood cells in liquid storage in CPD media.", "content": "A procedure which may distinguish between old and new CPD blood units in liquid state is described. It is based on the observation of increased tendency to reversible agglomeration in old erythrocytes in liquid preservation. Erythrocytes clump together when they are mixed with low ionic strength solutions in pH range of 5.2 to 6.5. We found that liquid-stored erythrocytes show an augmented tendency to agglomerate in 0.24M sucrose, pH 7.2. The tendency increases with storage so that in the fourth week, more than 70% of the units show agglomeration under these conditions. The addition of minute amounts of sodium chloride may prevent agglomeration. As the cells age, higher salt concentration is required to prevent agglomeration. A short incubation of washed cells with adenosine may reverse the tendency of outdated erythrocytes to agglomerate, concomitantly with reestablishment of initial ATP level. However, depletion of the ATP of fresh cells with fluoride does not induce agglomeration. A 20 hour incubation of units at 37 C with CPD revealed an increased sensitivity of older units, with low ATP and positive agglomeration. This test may help in distinguishing between outdated and younger units in the blood bank.", "contents": "Changes in agglomeration of human red blood cells in liquid storage in CPD media. A procedure which may distinguish between old and new CPD blood units in liquid state is described. It is based on the observation of increased tendency to reversible agglomeration in old erythrocytes in liquid preservation. Erythrocytes clump together when they are mixed with low ionic strength solutions in pH range of 5.2 to 6.5. We found that liquid-stored erythrocytes show an augmented tendency to agglomerate in 0.24M sucrose, pH 7.2. The tendency increases with storage so that in the fourth week, more than 70% of the units show agglomeration under these conditions. The addition of minute amounts of sodium chloride may prevent agglomeration. As the cells age, higher salt concentration is required to prevent agglomeration. A short incubation of washed cells with adenosine may reverse the tendency of outdated erythrocytes to agglomerate, concomitantly with reestablishment of initial ATP level. However, depletion of the ATP of fresh cells with fluoride does not induce agglomeration. A 20 hour incubation of units at 37 C with CPD revealed an increased sensitivity of older units, with low ATP and positive agglomeration. This test may help in distinguishing between outdated and younger units in the blood bank."}
{"id": "PMID:15349", "title": "Renal distal tubular secretory mechanisms in healthy Nigerian subjects.", "content": "The distal tubular secretory mechanisms of 30 healthy Nigerians were investigated. This entailed the collection of three different 24 hour urine samples; firstly basal values, secondly during the administration of 15 g of NH4Cl and finally when 5 g of KCl was given addition to 15 g NH4Cl. The basal 24 hour urinary volume was 1.36 litres with an average pH of 6.52 containing 42.74 mEq of combined acid and 114.5, 47.6 and 128.4 mEq Na+, K+ and CIce-ions respectively. During ammonium chloride ingestion the 24 hour urinary acid excretion rose to 72.35 mEq whilst the pH fell to 5.71. The values for Na+, K+ and CIce-were 183.2, 51.5 and 245 mEq respectively. When both NH4Cl and KCl were ingested urinary pH rose to 6.38, total acid excretion fell to 48.6 mEq whilst K+ excretion increased considerably to 172.1 mEq. This discussion stresses the point that though the healthy Nigerian may excrete lower values of H+ and K+ ions on the typical low protein diet; the renal distal secretory mechanism can respond appropriately when adequately challenged, as in this investigation.", "contents": "Renal distal tubular secretory mechanisms in healthy Nigerian subjects. The distal tubular secretory mechanisms of 30 healthy Nigerians were investigated. This entailed the collection of three different 24 hour urine samples; firstly basal values, secondly during the administration of 15 g of NH4Cl and finally when 5 g of KCl was given addition to 15 g NH4Cl. The basal 24 hour urinary volume was 1.36 litres with an average pH of 6.52 containing 42.74 mEq of combined acid and 114.5, 47.6 and 128.4 mEq Na+, K+ and CIce-ions respectively. During ammonium chloride ingestion the 24 hour urinary acid excretion rose to 72.35 mEq whilst the pH fell to 5.71. The values for Na+, K+ and CIce-were 183.2, 51.5 and 245 mEq respectively. When both NH4Cl and KCl were ingested urinary pH rose to 6.38, total acid excretion fell to 48.6 mEq whilst K+ excretion increased considerably to 172.1 mEq. This discussion stresses the point that though the healthy Nigerian may excrete lower values of H+ and K+ ions on the typical low protein diet; the renal distal secretory mechanism can respond appropriately when adequately challenged, as in this investigation."}
{"id": "PMID:15345", "title": "[Participation of pancreatic ribonuclease in the digestion processes].", "content": "The authors purified the alkaline ribonuclease obtained from the pancreas and the contents of the superior part of the dog's intestine. A comparative examination of physico-chemical properties and specificity of the separated enzymes was effected. The resulting data prove the pancreas to be the source of the alkaline ribonuclease contained in the superior portion of the intestine.", "contents": "[Participation of pancreatic ribonuclease in the digestion processes]. The authors purified the alkaline ribonuclease obtained from the pancreas and the contents of the superior part of the dog's intestine. A comparative examination of physico-chemical properties and specificity of the separated enzymes was effected. The resulting data prove the pancreas to be the source of the alkaline ribonuclease contained in the superior portion of the intestine."}
{"id": "PMID:15352", "title": "[pH measurements in the vascular wall of dogs with electrically induced thrombosis of the femoral artery].", "content": "Electrically induced thrombosis is often used for pathophysiologic and therapeutic experiments. The pH value of the vascular wall was measured to approach the features of this thrombosis. After inducing thrombosis by direct current, pH value of the intima of femoral artery was found decreased. The anode was inserted in the lumen. As to the behavior of the pH value, electric thrombosis and clinical thrombosis are similar. Electric thrombosis therefore seems to be valuable for comparing investigations.", "contents": "[pH measurements in the vascular wall of dogs with electrically induced thrombosis of the femoral artery]. Electrically induced thrombosis is often used for pathophysiologic and therapeutic experiments. The pH value of the vascular wall was measured to approach the features of this thrombosis. After inducing thrombosis by direct current, pH value of the intima of femoral artery was found decreased. The anode was inserted in the lumen. As to the behavior of the pH value, electric thrombosis and clinical thrombosis are similar. Electric thrombosis therefore seems to be valuable for comparing investigations."}
{"id": "PMID:15353", "title": "[Gas levels and biochemical changes in cerebrospinal fluid after experimental brain injury: its effect on cerebral circulation and cerebral metabolism as well as its management].", "content": "1. After brain damage experimentally induced by balloon compression, liquor of the cistern shows a metabolic acidosis with significantly increased lactate level and L/P quotient, and statistically distinct decrease of pH, oxygen tension, and bicarbonate level. 2. There is a considerable disproportion between the changes of acid-base metabolism, gas tension, and metabolic products in cerebrospinal fluid compared with much less expressed disturbances in the blood. 3. The advanced edematous phase shows distinct accumulation of water in the tissue, considerable increase of intracranial pressure, resp. decrease of effective perfusing pressure, loss of autoregulation, and decreased regional and global cerebral circulation, while the pathologic alterations of cerebral fluid are intensified. 4. Treatment of lactate acidosis in the liquor by intrathecal application of sodium bicarbonate results in improved cerebral circulation and metabolism of the cerebral tissue, having thus a good influence on cerebral damage and its sequels.", "contents": "[Gas levels and biochemical changes in cerebrospinal fluid after experimental brain injury: its effect on cerebral circulation and cerebral metabolism as well as its management]. 1. After brain damage experimentally induced by balloon compression, liquor of the cistern shows a metabolic acidosis with significantly increased lactate level and L/P quotient, and statistically distinct decrease of pH, oxygen tension, and bicarbonate level. 2. There is a considerable disproportion between the changes of acid-base metabolism, gas tension, and metabolic products in cerebrospinal fluid compared with much less expressed disturbances in the blood. 3. The advanced edematous phase shows distinct accumulation of water in the tissue, considerable increase of intracranial pressure, resp. decrease of effective perfusing pressure, loss of autoregulation, and decreased regional and global cerebral circulation, while the pathologic alterations of cerebral fluid are intensified. 4. Treatment of lactate acidosis in the liquor by intrathecal application of sodium bicarbonate results in improved cerebral circulation and metabolism of the cerebral tissue, having thus a good influence on cerebral damage and its sequels."}
{"id": "PMID:15346", "title": "[Glucose transport across the mucosa of the small intestine].", "content": "The rate of glucose absorption in an isolated loop of the small intestine in rats was measured. The maximum rate of absorption was registered with 3 and 5 per cent concentrations, while 1 and 10 per cent solutions are absorbed at a slower rate. The absorption rate of 5 per cent glucose solution did not materially change for one hour after a sugar load. The small intestine mucosa transports glucose from a 5 per cent solution at an equal rate in rats and rabbits, i. e. 139+/-4 and 143+/-6 gamma/cm2/min. Maximum absorption takes place with pH of 6-8. Deviation of the pH value to acidity and alkalinity is attended by steep fall in the absorption rate. At pH of 3.0 and 11.5 the absorption virtually ceases altogether. Hexobarbital anesthesia depresses absorption of glucose in the intestine by a factor of 2-3.5.", "contents": "[Glucose transport across the mucosa of the small intestine]. The rate of glucose absorption in an isolated loop of the small intestine in rats was measured. The maximum rate of absorption was registered with 3 and 5 per cent concentrations, while 1 and 10 per cent solutions are absorbed at a slower rate. The absorption rate of 5 per cent glucose solution did not materially change for one hour after a sugar load. The small intestine mucosa transports glucose from a 5 per cent solution at an equal rate in rats and rabbits, i. e. 139+/-4 and 143+/-6 gamma/cm2/min. Maximum absorption takes place with pH of 6-8. Deviation of the pH value to acidity and alkalinity is attended by steep fall in the absorption rate. At pH of 3.0 and 11.5 the absorption virtually ceases altogether. Hexobarbital anesthesia depresses absorption of glucose in the intestine by a factor of 2-3.5."}
{"id": "PMID:15354", "title": "[Fetal heart rate, dip area and acid base observations in breech and vertex deliveries (author's transl)].", "content": "Fetal heart rate (FHR), dip area (DA) and the acid base status (AB) were investigated in breech deliveries (BD) (N= 167) and in group of spontaneously delivered vertex presentations (VP) (NFHR, DA=50; NAB=109). 90 minutes prior to delivery fetal heart rate and dip area were in both groups not significantly different. However as labor progressed the fetal heart rate as well as dip area increased in breech deliveries much more (FHR 163 (SD 16.2) beats/min, DA 1,07 (SD 0,80) cm2/min) than in VP (FHR 136 (SD 14,8) beats/min, DA 0,65 (SD 0,39) cm2/min) (2p less than 0,001). The base excess of the umbilical arterial blood was correlated to the DA measured from 10 minutes prior to birth till the delivery of the baby: BE =  -8,2 --0,3 (DA) (2alpha less than 0,01). The frequency of acidotic babies was more in vaginally delivered breech presentations (pH less than 7,20 = 30, 2%, BE greater than -10 meq/l = 43,7%) than in breech deliveries by caesarean section (pH less than 7,20 = 19,1%, BE greater than -10 meq/l = 24,4%) and vertex presentations (pH less than 7,20 - 5,5%, BE greater than -10 meq/l = 14,6%), respectively. The distance between the vertex and the umbilicus was 28 cm and between the breech and the umbilicus 9,4 cm. From this anatomical observation it is concluded that umbilical cord compression, preferentially umbilicai vein occlusion takes place in breech presentation at an earlier point on than in vertex presentation. The rise of fetal heart rate and the increase in dip area are showing in addition that the fetal buffer base in breech presentation will be reduced during the last time course of the second stage of labor.", "contents": "[Fetal heart rate, dip area and acid base observations in breech and vertex deliveries (author's transl)]. Fetal heart rate (FHR), dip area (DA) and the acid base status (AB) were investigated in breech deliveries (BD) (N= 167) and in group of spontaneously delivered vertex presentations (VP) (NFHR, DA=50; NAB=109). 90 minutes prior to delivery fetal heart rate and dip area were in both groups not significantly different. However as labor progressed the fetal heart rate as well as dip area increased in breech deliveries much more (FHR 163 (SD 16.2) beats/min, DA 1,07 (SD 0,80) cm2/min) than in VP (FHR 136 (SD 14,8) beats/min, DA 0,65 (SD 0,39) cm2/min) (2p less than 0,001). The base excess of the umbilical arterial blood was correlated to the DA measured from 10 minutes prior to birth till the delivery of the baby: BE =  -8,2 --0,3 (DA) (2alpha less than 0,01). The frequency of acidotic babies was more in vaginally delivered breech presentations (pH less than 7,20 = 30, 2%, BE greater than -10 meq/l = 43,7%) than in breech deliveries by caesarean section (pH less than 7,20 = 19,1%, BE greater than -10 meq/l = 24,4%) and vertex presentations (pH less than 7,20 - 5,5%, BE greater than -10 meq/l = 14,6%), respectively. The distance between the vertex and the umbilicus was 28 cm and between the breech and the umbilicus 9,4 cm. From this anatomical observation it is concluded that umbilical cord compression, preferentially umbilicai vein occlusion takes place in breech presentation at an earlier point on than in vertex presentation. The rise of fetal heart rate and the increase in dip area are showing in addition that the fetal buffer base in breech presentation will be reduced during the last time course of the second stage of labor."}
{"id": "PMID:15347", "title": "[Protein hydrolysis by pepsin and trypsin at a varying pH].", "content": "The continuity of the pepsin and trysin action on the proteinic substrates with different pH was studied. A short-term incubation of protein with pepsin at high pH intensifies the tryptic effect on this protein, the initial rate of the protein hydrolysis then gains momentum and the possibility of its complete hydrolysis increases over the same period of time. With successive action of fibrin of the gastric and pancreatic secretions prinicipally the same relationship has been established.", "contents": "[Protein hydrolysis by pepsin and trypsin at a varying pH]. The continuity of the pepsin and trysin action on the proteinic substrates with different pH was studied. A short-term incubation of protein with pepsin at high pH intensifies the tryptic effect on this protein, the initial rate of the protein hydrolysis then gains momentum and the possibility of its complete hydrolysis increases over the same period of time. With successive action of fibrin of the gastric and pancreatic secretions prinicipally the same relationship has been established."}
{"id": "PMID:15355", "title": "Nanoencapsulated fluorescence indicator molecules measuring pH and pO2 down to submicroscopical regions in the basis of the optode-principle.", "content": "To measure pO2 in gases or fluids and pH in solutions the fluorescence indicators pyrene butyric acid and beta-methylumbelliferone, respectively, were nanoencapsulated to obtain nano-probes for measurement in physiological structures of nano-range. For pH the fluorescence changes of beta-methylumbelliferone were monitored, for pO2 the fluoresence quenching of pyrene butyric acid by oxygen were registered. Drawing log (S1/S2) versus pH, one obtains a straight line between the pH from 6 to 8. A linear increase in pO2 between 0 and 400 torr yields a linear increase in the reciprocal fluorescence signal.", "contents": "Nanoencapsulated fluorescence indicator molecules measuring pH and pO2 down to submicroscopical regions in the basis of the optode-principle. To measure pO2 in gases or fluids and pH in solutions the fluorescence indicators pyrene butyric acid and beta-methylumbelliferone, respectively, were nanoencapsulated to obtain nano-probes for measurement in physiological structures of nano-range. For pH the fluorescence changes of beta-methylumbelliferone were monitored, for pO2 the fluoresence quenching of pyrene butyric acid by oxygen were registered. Drawing log (S1/S2) versus pH, one obtains a straight line between the pH from 6 to 8. A linear increase in pO2 between 0 and 400 torr yields a linear increase in the reciprocal fluorescence signal."}
{"id": "PMID:15356", "title": "Effects of phospholipids in the action of acetyl-CoA carboxylase from rat liver.", "content": "Acetyl-CoA carboxylase (E.C. 6.4.1.2) was isolated from rat liver. The purified enzyme contains phospholipids with a rather large amount of phosphatidylinositol (26%). Incubation of the purified acetyl-CoA carboxylase with phospholipase A2 (E.C. 3.1.1.4) or with phospholipase D (E.C. 3.1.1.4) diminishes the phospholipid content by 70%, this treatment leading to a complete inactivation of the enzyme. After removal of the phospholipases, the lipid-depleted enzyme can be reactivated to a certain degree by incubation with a phospholipid extract from rat liver, with phosphatidylinositol alone, or with serum albumin.", "contents": "Effects of phospholipids in the action of acetyl-CoA carboxylase from rat liver. Acetyl-CoA carboxylase (E.C. 6.4.1.2) was isolated from rat liver. The purified enzyme contains phospholipids with a rather large amount of phosphatidylinositol (26%). Incubation of the purified acetyl-CoA carboxylase with phospholipase A2 (E.C. 3.1.1.4) or with phospholipase D (E.C. 3.1.1.4) diminishes the phospholipid content by 70%, this treatment leading to a complete inactivation of the enzyme. After removal of the phospholipases, the lipid-depleted enzyme can be reactivated to a certain degree by incubation with a phospholipid extract from rat liver, with phosphatidylinositol alone, or with serum albumin."}
{"id": "PMID:15368", "title": "The effect Escherichia coli lipopolysaccharide (endotoxin) on the graft-versus-host reaction in mice (IV).", "content": "Lipopolysaccharide from Escherichia coli (LPS) administered to mice during the graft-versus-host (GvH) reaction in a single dose of 100 mug stimulated the reaction if it was given on the same day as the parental spleen cells, or inhibited it if given four days before injection of the cells. The GvH reaction was intensified when LPS was injected in the dose of 20 mug on the fourth day after injection of the cells. The parental spleen cells responsible for the intestifying effect on GvH were sensitive to hydrocortisone, nonadherent, and probably develop in the course of the first week outside the donor spleen and settle in the spleen in a later stage of the GvH reaction.", "contents": "The effect Escherichia coli lipopolysaccharide (endotoxin) on the graft-versus-host reaction in mice (IV). Lipopolysaccharide from Escherichia coli (LPS) administered to mice during the graft-versus-host (GvH) reaction in a single dose of 100 mug stimulated the reaction if it was given on the same day as the parental spleen cells, or inhibited it if given four days before injection of the cells. The GvH reaction was intensified when LPS was injected in the dose of 20 mug on the fourth day after injection of the cells. The parental spleen cells responsible for the intestifying effect on GvH were sensitive to hydrocortisone, nonadherent, and probably develop in the course of the first week outside the donor spleen and settle in the spleen in a later stage of the GvH reaction."}
{"id": "PMID:15389", "title": "Age-dependent resistance of chicken of Salmonella in vitro: antibacterial activity of lysed granule fraction of splenic adherent cells.", "content": "Lysed granule fraction was prepared from splenic adherent cells from 0-day-old to 2-month-old chickens and was examined antibacterial activity to Salmonella pullorum and Salmonella sentfenberg. The activity of lysed granule fraction from 2-month-old chickens was exhibited at pH 5.0 but not exhibited at pH 6.0 or 7.0 to both serotypes of Salmonella. At pH 5.0, lysed granule fraction from 0-day-old chickens revealed little antibacterial activity to S. pullorum but the activity increased with increasing age. At 240 min of incubation, 60% and 95% of S. pullorum were inactivated in lysed granule fractions from 7-day-old and 2-month-old chickens, respectively. High antibacterial activity to S. senftenberg was observed in lysed granule fraction from 2-month-old chickens in which 99.6% of the bacteria was inactivated during 240 min; In lysed granule fractions from 0-day old and 7-day-old chickens, 90% of S. senftenberg was inactivated during 60 min but the number of bacteria increased conversely after incubation for 240 min. Changes in enzymatic activities of 4 enzymes in the lysed granule fractions from various ages of chickens were examined. beta-Glucronidase increased statistically significantly to 2.4 and 7.6 times from 0-day-old to 7-day-old and 2-month-old chickens, respectively. Acid phosphatase and alkaline phosphatase increased slightly but not significantly different, and enzymatic activity of myeloperoxidase was scarcely detected.", "contents": "Age-dependent resistance of chicken of Salmonella in vitro: antibacterial activity of lysed granule fraction of splenic adherent cells. Lysed granule fraction was prepared from splenic adherent cells from 0-day-old to 2-month-old chickens and was examined antibacterial activity to Salmonella pullorum and Salmonella sentfenberg. The activity of lysed granule fraction from 2-month-old chickens was exhibited at pH 5.0 but not exhibited at pH 6.0 or 7.0 to both serotypes of Salmonella. At pH 5.0, lysed granule fraction from 0-day-old chickens revealed little antibacterial activity to S. pullorum but the activity increased with increasing age. At 240 min of incubation, 60% and 95% of S. pullorum were inactivated in lysed granule fractions from 7-day-old and 2-month-old chickens, respectively. High antibacterial activity to S. senftenberg was observed in lysed granule fraction from 2-month-old chickens in which 99.6% of the bacteria was inactivated during 240 min; In lysed granule fractions from 0-day old and 7-day-old chickens, 90% of S. senftenberg was inactivated during 60 min but the number of bacteria increased conversely after incubation for 240 min. Changes in enzymatic activities of 4 enzymes in the lysed granule fractions from various ages of chickens were examined. beta-Glucronidase increased statistically significantly to 2.4 and 7.6 times from 0-day-old to 7-day-old and 2-month-old chickens, respectively. Acid phosphatase and alkaline phosphatase increased slightly but not significantly different, and enzymatic activity of myeloperoxidase was scarcely detected."}
{"id": "PMID:15390", "title": "[Pigment Formation by Trichophyton rubrum: Differentiation between T. rubrum and T. mentagrophytes on Serum Albumin Agar (author's transl)].", "content": "On serum albumin agar (bovine albumin) with initial pH-values of 5.0-6.0, Trichophyton rubrum showed a yellow pigmentation, and on the same medium with an initial pH-value of 7.0, a red pigmentation. Strains of Trichophyton mentagrophytes have never shown pigmentation until now, The scarce growth (submerged) of T. rubrum on serum albumin agar is associated with a pigment formation that may be used for diagnostic purposes. It could be read within 3-7 days. Serum albumin agar with the initial pH-value of 5.0 was introduced in 1964 for the detection of the strain-specific proteolytic activity of Candida albicans.", "contents": "[Pigment Formation by Trichophyton rubrum: Differentiation between T. rubrum and T. mentagrophytes on Serum Albumin Agar (author's transl)]. On serum albumin agar (bovine albumin) with initial pH-values of 5.0-6.0, Trichophyton rubrum showed a yellow pigmentation, and on the same medium with an initial pH-value of 7.0, a red pigmentation. Strains of Trichophyton mentagrophytes have never shown pigmentation until now, The scarce growth (submerged) of T. rubrum on serum albumin agar is associated with a pigment formation that may be used for diagnostic purposes. It could be read within 3-7 days. Serum albumin agar with the initial pH-value of 5.0 was introduced in 1964 for the detection of the strain-specific proteolytic activity of Candida albicans."}
{"id": "PMID:15392", "title": "[Pathogenic factors in viral diseases of the central nervous system].", "content": "The possible immunological significance of the different kinds of cells participating in the inflammatory reaction in cerebrospinal infections is to be considered. Presence of plasma cells and occasional perivenous microglial seams in early stages of the neurotropic virus diseases must be regarded as immunological manifestations. The brainstem nuclei are sites of predilection both in entero- and in arbovirus diseases. The aetiologically different neurotropic virus diseases obtain their individual character from the involvement of certain neurones. Neural pathways are to be taken into consideration mainly for the propagation of enteroviruses, but may have a part also in the propagation of arboviruses. With massive invasion by highly cytopathogenic viruses inflammatory reaction may fail to appear in the immature nervous tissue. Some encephalitides, of both viral and non-viral aetiology, in which the prevalence of plasma cells in the infiltrations bears evidence of an intense immune process, may be interpreted as immunologically determined late diseases.", "contents": "[Pathogenic factors in viral diseases of the central nervous system]. The possible immunological significance of the different kinds of cells participating in the inflammatory reaction in cerebrospinal infections is to be considered. Presence of plasma cells and occasional perivenous microglial seams in early stages of the neurotropic virus diseases must be regarded as immunological manifestations. The brainstem nuclei are sites of predilection both in entero- and in arbovirus diseases. The aetiologically different neurotropic virus diseases obtain their individual character from the involvement of certain neurones. Neural pathways are to be taken into consideration mainly for the propagation of enteroviruses, but may have a part also in the propagation of arboviruses. With massive invasion by highly cytopathogenic viruses inflammatory reaction may fail to appear in the immature nervous tissue. Some encephalitides, of both viral and non-viral aetiology, in which the prevalence of plasma cells in the infiltrations bears evidence of an intense immune process, may be interpreted as immunologically determined late diseases."}
{"id": "PMID:15393", "title": "ATP-ase activity in the odontoblastic layer of rat incisor. Determination with a radiochemical and a colorimetric method.", "content": "The ATP-splitting enzyme activity in odontoblasts isolated from rat incisors has been studied by means of a radiochemical and a colorimetric micromethod. The results with the two methods were virtually identical. The reaction was linear with time for at least 45 min. The pH optimum was found to be 9.8 independently of the ATP concentration. Maximal substrate saturation occurred at a total ATP concentration of 3 mM. Ca2+ and Mg2+ ions activated ATP degradation. F-ions did not affect the activity at low concentrations, whereas higher concentrations were inhibitory. Na+ and ions were slightly inhibitory. Urea inhibited the enzyme activity at concentrations  above 1.5 M, while EDTA and EGTA were strong inhibitors at very low concentrations. When incubating in the presence of low concentrations of specific inhibitors for nonspecific alkaline phosphatase, levamisole and R8231, about 20% ATP degrading enzyme activity remained. In conclusion it is suggested that there are at least two ATP degrading phosphatases active at alkaline pH.", "contents": "ATP-ase activity in the odontoblastic layer of rat incisor. Determination with a radiochemical and a colorimetric method. The ATP-splitting enzyme activity in odontoblasts isolated from rat incisors has been studied by means of a radiochemical and a colorimetric micromethod. The results with the two methods were virtually identical. The reaction was linear with time for at least 45 min. The pH optimum was found to be 9.8 independently of the ATP concentration. Maximal substrate saturation occurred at a total ATP concentration of 3 mM. Ca2+ and Mg2+ ions activated ATP degradation. F-ions did not affect the activity at low concentrations, whereas higher concentrations were inhibitory. Na+ and ions were slightly inhibitory. Urea inhibited the enzyme activity at concentrations  above 1.5 M, while EDTA and EGTA were strong inhibitors at very low concentrations. When incubating in the presence of low concentrations of specific inhibitors for nonspecific alkaline phosphatase, levamisole and R8231, about 20% ATP degrading enzyme activity remained. In conclusion it is suggested that there are at least two ATP degrading phosphatases active at alkaline pH."}
{"id": "PMID:15394", "title": "Characterization of kallikrein from human saliva isolated by use of affinity chromatography.", "content": "Kallikrein was isolated from paraffin stimulated saliva by use of two steps affinity chromatography. A610-fold purification of the enzyme was achieved by use of Sepharose 4B conjugated with soy bean trypsin inhibitor and pancreatic trypsin inhibitor. The isoelectric point of kallikrein was found to be pH 4.3 and the molecular weight was calculated to be about 38.000 by gel filtration on a AcA44 Ultrogel column. The enzyme had a pH optimum at pH 8.6 using BAEE and TAME as substrates. The michaelis constant for kallikrein on these two substrates was 4.0-10(-4) M and 5.5-10(-4)M. respectively.", "contents": "Characterization of kallikrein from human saliva isolated by use of affinity chromatography. Kallikrein was isolated from paraffin stimulated saliva by use of two steps affinity chromatography. A610-fold purification of the enzyme was achieved by use of Sepharose 4B conjugated with soy bean trypsin inhibitor and pancreatic trypsin inhibitor. The isoelectric point of kallikrein was found to be pH 4.3 and the molecular weight was calculated to be about 38.000 by gel filtration on a AcA44 Ultrogel column. The enzyme had a pH optimum at pH 8.6 using BAEE and TAME as substrates. The michaelis constant for kallikrein on these two substrates was 4.0-10(-4) M and 5.5-10(-4)M. respectively."}
{"id": "PMID:15395", "title": "Characterization of trypsin-like enzymes from human saliva isolated by use of affinity chromatography.", "content": "Paraffin-stimulated whole mixed saliva was collected from 6 individuals and pooled. Three trypsin-like enzymes from saliva supernatant and two from the saliva sediment were isolated by use of affinity chromatography on a soybean trypsin inhibitor Sepharose 4 B column. The isoelectric points for these enzymes were pI 8.0, 6.8 and 6.4 from the supernatant and  6.4 and 6.2 from the sediment. The enzymes were characterized with respect to pH-optimum, pH-stability, temperature stability, substrate specificity and influence of metal ions and inhibitors. The Michaelis constants were determined for these enzymes on the substrates BAEE and TAME.", "contents": "Characterization of trypsin-like enzymes from human saliva isolated by use of affinity chromatography. Paraffin-stimulated whole mixed saliva was collected from 6 individuals and pooled. Three trypsin-like enzymes from saliva supernatant and two from the saliva sediment were isolated by use of affinity chromatography on a soybean trypsin inhibitor Sepharose 4 B column. The isoelectric points for these enzymes were pI 8.0, 6.8 and 6.4 from the supernatant and  6.4 and 6.2 from the sediment. The enzymes were characterized with respect to pH-optimum, pH-stability, temperature stability, substrate specificity and influence of metal ions and inhibitors. The Michaelis constants were determined for these enzymes on the substrates BAEE and TAME."}
{"id": "PMID:15396", "title": "Myxofibrosarcoma. A study of 30 cases.", "content": "A series of 30 myxofibrosarcomas is described. These malignant soft tissue tumours are characterized by a mucoid and nodular appearance, a coarse plexiform capillary pattern, and they are mostly seen subcutaneously (26 out of 30) in the extremities (24 out of 30) and trunk (4 out of 30) elderly people. Histochemical studies, comprising staining with Alcian blue and toluidine blue at different pH's with and without preceding digestion with testicular hyaluronidase and with the Scott technique, indicated the presence of hyaluronic acid but not sulphated glycosaminoglycans as chondroitinsulphates. Myxofibrosarcoma is believed to belong to the general category of fibroblastic and histiocytic malignant soft tissue tumours. The median diameter of the tumours was 7 cm. They were divided into 4 grades according to cellularity, cell atypia and mitotic activity. The grade III and IV tumours showed pronounced atypia, often with the bi- and multinucleated giant tumour cells and occasionally with giant cells of Touton's type, suggesting a relationship to malignant fibroxanthoma. All of the patients were treated surgically and one received also pre- and post-operative irradiation. None of the 2 grade I myxofibrosarcomas recurred, while 2 out of 7 grade II tumours, 6 out of 10 grade III tumours, and 7 out of 11 grade IV tumours recurred once and up to 9 times. Metastasis appeared in 7 out of 30 patients; grade I tumours were not seen in any of these cases. By the time of follow-up after intervals ranging from 1 month up to 27 years, 14 patients had died; 6 of these had died post-operatively or of intercurrent disease. The differential diagnosis between myxofibrosarcoma and other myxoid soft tissue tumours is discussed.", "contents": "Myxofibrosarcoma. A study of 30 cases. A series of 30 myxofibrosarcomas is described. These malignant soft tissue tumours are characterized by a mucoid and nodular appearance, a coarse plexiform capillary pattern, and they are mostly seen subcutaneously (26 out of 30) in the extremities (24 out of 30) and trunk (4 out of 30) elderly people. Histochemical studies, comprising staining with Alcian blue and toluidine blue at different pH's with and without preceding digestion with testicular hyaluronidase and with the Scott technique, indicated the presence of hyaluronic acid but not sulphated glycosaminoglycans as chondroitinsulphates. Myxofibrosarcoma is believed to belong to the general category of fibroblastic and histiocytic malignant soft tissue tumours. The median diameter of the tumours was 7 cm. They were divided into 4 grades according to cellularity, cell atypia and mitotic activity. The grade III and IV tumours showed pronounced atypia, often with the bi- and multinucleated giant tumour cells and occasionally with giant cells of Touton's type, suggesting a relationship to malignant fibroxanthoma. All of the patients were treated surgically and one received also pre- and post-operative irradiation. None of the 2 grade I myxofibrosarcomas recurred, while 2 out of 7 grade II tumours, 6 out of 10 grade III tumours, and 7 out of 11 grade IV tumours recurred once and up to 9 times. Metastasis appeared in 7 out of 30 patients; grade I tumours were not seen in any of these cases. By the time of follow-up after intervals ranging from 1 month up to 27 years, 14 patients had died; 6 of these had died post-operatively or of intercurrent disease. The differential diagnosis between myxofibrosarcoma and other myxoid soft tissue tumours is discussed."}
{"id": "PMID:15399", "title": "Disposition of three benzodiazepines after single oral administration in man.", "content": "Three benzodiazepines in equipotent doses: oxazepam 15 mg, dipotassium chlorazepate 10 mg and diazepam 5 mg, were administered in single, oral doses to seven healthy volunteers in a three-way cross-over study. The serum concentrations of oxazepam, N-desmethyldiazepam and diazepam were followed for 72 hours by gas chromatography and electron capture detection. The absorption of diazepam was most rapid and the mean time required to reach peak serum concentration was 45 minutes, followed by N-desmethyldiazepam 80 minutes and oxazepam 114 minutes. The serum concentration decay curves were biphasic with terminal mean half-lives of 48, 62 and 11 hours for diazepam, N-desmethyldiazepam and oxazepam, respectively. The mean and individual serum concentration time data were fitted to a two-compartment open model with first order absorption using a non linear least square program. The mean serum data fitted the model well. The same rank order was obtained with mean absorption half-lives as when comparing mean peak times while slightly shorter terminal half-lives were obtained in the curve fitting of mean serum data. Due to irregularities in the serum concentration time curves only five out of the 21 sets of individual data could satisfy the convergence criterion. The obtained parameters in the curve fitting were also accompanied with very large asymptotic standard deviations.", "contents": "Disposition of three benzodiazepines after single oral administration in man. Three benzodiazepines in equipotent doses: oxazepam 15 mg, dipotassium chlorazepate 10 mg and diazepam 5 mg, were administered in single, oral doses to seven healthy volunteers in a three-way cross-over study. The serum concentrations of oxazepam, N-desmethyldiazepam and diazepam were followed for 72 hours by gas chromatography and electron capture detection. The absorption of diazepam was most rapid and the mean time required to reach peak serum concentration was 45 minutes, followed by N-desmethyldiazepam 80 minutes and oxazepam 114 minutes. The serum concentration decay curves were biphasic with terminal mean half-lives of 48, 62 and 11 hours for diazepam, N-desmethyldiazepam and oxazepam, respectively. The mean and individual serum concentration time data were fitted to a two-compartment open model with first order absorption using a non linear least square program. The mean serum data fitted the model well. The same rank order was obtained with mean absorption half-lives as when comparing mean peak times while slightly shorter terminal half-lives were obtained in the curve fitting of mean serum data. Due to irregularities in the serum concentration time curves only five out of the 21 sets of individual data could satisfy the convergence criterion. The obtained parameters in the curve fitting were also accompanied with very large asymptotic standard deviations."}
{"id": "PMID:15400", "title": "Biological studies on the effects of some therapeutic procedures used in psychiatry.", "content": "The glucose, lactate, and pyruvate levels, the lactate/pyruvate ratio and pH were studied in serum and CSF of patients with schizophrenia, reactive psychosis, symptomatic or circular psychosis under the effect of atropine coma, ES and pentetrazole convulsions, tranquilizer treatment and combined therapy. Convulsive therapy caused a disorder in cerebral carbohydrate metabolism while no similar changes were induced by atropine coma. Anaerobic carbohydrate metabolism was stimulated by combined therapy. This treatment had the best effect and the changes caused by it were slighter than in the case of convulsive therapy. The changes in EEG frequency corresponded to the biochemical changes.", "contents": "Biological studies on the effects of some therapeutic procedures used in psychiatry. The glucose, lactate, and pyruvate levels, the lactate/pyruvate ratio and pH were studied in serum and CSF of patients with schizophrenia, reactive psychosis, symptomatic or circular psychosis under the effect of atropine coma, ES and pentetrazole convulsions, tranquilizer treatment and combined therapy. Convulsive therapy caused a disorder in cerebral carbohydrate metabolism while no similar changes were induced by atropine coma. Anaerobic carbohydrate metabolism was stimulated by combined therapy. This treatment had the best effect and the changes caused by it were slighter than in the case of convulsive therapy. The changes in EEG frequency corresponded to the biochemical changes."}
{"id": "PMID:15401", "title": "Solubilization of particle-linked urate oxidase by different agents.", "content": "Urate oxidase was mostly recovered in a 40 000 g for 20 min subcellular fraction from conventional homogenated. Different agents were able to solubilize the sedimentable enzyme when tested on this crude peroxisomal fraction. The agents increased also total enzyme activity which was recovered in supernatants after centfiguation. If the possible effect of absorption to pellets is to be discounted, the enzyme was practically 100% extracted by six alternated freezing and thawing high alkaline pH, the detergent Hyamine 2389 and high ionic strength of calcium chloride. Triton X-100 was very effective in extracting proteins from the fraction, while it left most of the enzyme activity insoluble. It is suggested that the forces responsible for the integrity of the crystalloid, which was observed by other authors at the electron microscope, and to which the enzyme is believed to be related, are the electrostatic nature.", "contents": "Solubilization of particle-linked urate oxidase by different agents. Urate oxidase was mostly recovered in a 40 000 g for 20 min subcellular fraction from conventional homogenated. Different agents were able to solubilize the sedimentable enzyme when tested on this crude peroxisomal fraction. The agents increased also total enzyme activity which was recovered in supernatants after centfiguation. If the possible effect of absorption to pellets is to be discounted, the enzyme was practically 100% extracted by six alternated freezing and thawing high alkaline pH, the detergent Hyamine 2389 and high ionic strength of calcium chloride. Triton X-100 was very effective in extracting proteins from the fraction, while it left most of the enzyme activity insoluble. It is suggested that the forces responsible for the integrity of the crystalloid, which was observed by other authors at the electron microscope, and to which the enzyme is believed to be related, are the electrostatic nature."}
{"id": "PMID:15402", "title": "Effects of acetylsalicylate on alkalinization, acid secretion and electrogenic properties in the isolated gastric mucosa.", "content": "The effects of acetylsalicylate (ASA) on the in vitro secretory and electrical properties of Necturus and Rana temporaria gastric mucosa have been studied. The gastric antrum alkalinized the luminal surface, while in the fundus it is likely that acidificaiton and alkalinization occur simultaneously and that net secretion is due to the dominance of one or other of these processes. The histamine H2  receptor antagonist Metiamide was used to inhibit acid secretion for studies on fundic alkalinization in Rana temporaria. Submucosal application of 3 mM ASA for 30 min markedly reduced alkalinization in the antrum and the frog fundus. Following removal of ASA there was only partial recovery of this secretion. The drug caused slight inhibtion of spontaneous acid secretion in Necturus fundus but not of histamine-stimulated acid secretion in the frog fundus. Following salicylate removal, the rate of acid secretion increased to a higher level than before administration in both tissues. There was a small flux of ASA across the mucosa which was greatest in the acid secreting frog fundus (4.38mumol cm-2 min-1) and least in the antrum (2.19 mumol cm-2 min-1). Esposure of the gastric mucosa to ASA was generally associated with a fall in transmucosal electric potential difference and short-circuit current together with an increase in electrical resistance. It is proposed that the greater sensitivity of alkalinization to ASA is responsible for the apparent increase in the rate of acid secretion which occured.", "contents": "Effects of acetylsalicylate on alkalinization, acid secretion and electrogenic properties in the isolated gastric mucosa. The effects of acetylsalicylate (ASA) on the in vitro secretory and electrical properties of Necturus and Rana temporaria gastric mucosa have been studied. The gastric antrum alkalinized the luminal surface, while in the fundus it is likely that acidificaiton and alkalinization occur simultaneously and that net secretion is due to the dominance of one or other of these processes. The histamine H2  receptor antagonist Metiamide was used to inhibit acid secretion for studies on fundic alkalinization in Rana temporaria. Submucosal application of 3 mM ASA for 30 min markedly reduced alkalinization in the antrum and the frog fundus. Following removal of ASA there was only partial recovery of this secretion. The drug caused slight inhibtion of spontaneous acid secretion in Necturus fundus but not of histamine-stimulated acid secretion in the frog fundus. Following salicylate removal, the rate of acid secretion increased to a higher level than before administration in both tissues. There was a small flux of ASA across the mucosa which was greatest in the acid secreting frog fundus (4.38mumol cm-2 min-1) and least in the antrum (2.19 mumol cm-2 min-1). Esposure of the gastric mucosa to ASA was generally associated with a fall in transmucosal electric potential difference and short-circuit current together with an increase in electrical resistance. It is proposed that the greater sensitivity of alkalinization to ASA is responsible for the apparent increase in the rate of acid secretion which occured."}
{"id": "PMID:15403", "title": "Lower body negative pressure and effects of autonomic heart blockade on cardiovascular responses.", "content": "Heart rate, arterial pressure and cardiac output were recorded in eight healthy male volunteers during exposure to 80 mmHg of lower body negative pressure (LBNP) in the supine position before and after beta-adrenergic and combined beta-adrenergic and parasympathetic blockade of the heart as induced by the i.v. administration of propranolol 0.25 mg/kg b.wt. and atropine 0.04 mg/kg b.wt. After propranolol, heart rate response to LBNP averaged 48% of that observed without blockade indicating that LBNP-induced cardioacceleration is of both sympathetic and parasympathetic origin. Tolerance to LBNP was reduced by beta-adrenergic blockade, since the decrease in mean arterial pressure during LBNP was exaggerated by such blockade. Although the addition of atropine markedly elevated mean arterial pressure and cardiac output in the control situation, tolerance to LBNP was not enhanced by this drug as judged from the arterial pressure response. Post-LBNP overshoot in mean arterial pressure was strikingly augmented by combined cardiac effector blockade and was in part due to a lingering elevation of total peripheral resistance, cardiac output remaining decreased for more than 110 s after release of LBNP.", "contents": "Lower body negative pressure and effects of autonomic heart blockade on cardiovascular responses. Heart rate, arterial pressure and cardiac output were recorded in eight healthy male volunteers during exposure to 80 mmHg of lower body negative pressure (LBNP) in the supine position before and after beta-adrenergic and combined beta-adrenergic and parasympathetic blockade of the heart as induced by the i.v. administration of propranolol 0.25 mg/kg b.wt. and atropine 0.04 mg/kg b.wt. After propranolol, heart rate response to LBNP averaged 48% of that observed without blockade indicating that LBNP-induced cardioacceleration is of both sympathetic and parasympathetic origin. Tolerance to LBNP was reduced by beta-adrenergic blockade, since the decrease in mean arterial pressure during LBNP was exaggerated by such blockade. Although the addition of atropine markedly elevated mean arterial pressure and cardiac output in the control situation, tolerance to LBNP was not enhanced by this drug as judged from the arterial pressure response. Post-LBNP overshoot in mean arterial pressure was strikingly augmented by combined cardiac effector blockade and was in part due to a lingering elevation of total peripheral resistance, cardiac output remaining decreased for more than 110 s after release of LBNP."}
{"id": "PMID:15405", "title": "Partial correction of hypertension by angiotensin II blockade in a patient with phaeochromocytoma.", "content": "This case report describes a patient with malignant hypertension and phaeochromocytoma in whom blockade of angiotensin II receptors by the competitive antagonist 1-sar-8-ala-angiotensin II (Saralasin) resulted in a partial correction of the elevated BP. Plasma renin activity was high and rose further during the blockade. Competitive inhibition of angiotensin II by Saralasin does not abolish the pressor effect of catecholamines. It was therefore interesting to observe that in this patient with phaeochromocytoma, independently, both alpha-adrenergic receptor blockade and angiotensin II receptor blockade were effective in lowering BP.", "contents": "Partial correction of hypertension by angiotensin II blockade in a patient with phaeochromocytoma. This case report describes a patient with malignant hypertension and phaeochromocytoma in whom blockade of angiotensin II receptors by the competitive antagonist 1-sar-8-ala-angiotensin II (Saralasin) resulted in a partial correction of the elevated BP. Plasma renin activity was high and rose further during the blockade. Competitive inhibition of angiotensin II by Saralasin does not abolish the pressor effect of catecholamines. It was therefore interesting to observe that in this patient with phaeochromocytoma, independently, both alpha-adrenergic receptor blockade and angiotensin II receptor blockade were effective in lowering BP."}
{"id": "PMID:15407", "title": "Neurochemical evidence for histamine acting as a transmitter in mammalian brain.", "content": "HA, besides its function in immune processes, is probably a neurotransmitter in mammalian brain. It is synthesized by a specific decarboxylase localized in the cytoplasm of nerve endings. It is stored in synaptic vesicles. Its release might depend on nerve-impulse flow; specific receptors to this amine have been evidenced both electrophysiologically and by the activation of cyclic AMP formation. Lesion studies indicate that histamine-containing neurons might constitute an ascending bundle arising from the brainstem and widely projecting into the whole telencephalon. This disposition, together with neuropharmacological data, suggests that histaminergic neurons, like the monoaminergic ones, might be involved in the control of arousal mechanisms, an idea consistent with the observed fluctuations of the endogenous amine content during the day-night cycle. On the other hand, the investigation of the effect of stress situations on the turnover of HA in brain leads to the conclusion that histaminergic neurons are specifically affected.", "contents": "Neurochemical evidence for histamine acting as a transmitter in mammalian brain. HA, besides its function in immune processes, is probably a neurotransmitter in mammalian brain. It is synthesized by a specific decarboxylase localized in the cytoplasm of nerve endings. It is stored in synaptic vesicles. Its release might depend on nerve-impulse flow; specific receptors to this amine have been evidenced both electrophysiologically and by the activation of cyclic AMP formation. Lesion studies indicate that histamine-containing neurons might constitute an ascending bundle arising from the brainstem and widely projecting into the whole telencephalon. This disposition, together with neuropharmacological data, suggests that histaminergic neurons, like the monoaminergic ones, might be involved in the control of arousal mechanisms, an idea consistent with the observed fluctuations of the endogenous amine content during the day-night cycle. On the other hand, the investigation of the effect of stress situations on the turnover of HA in brain leads to the conclusion that histaminergic neurons are specifically affected."}
{"id": "PMID:15417", "title": "Purine nucleotides.", "content": "The existence of nonadrenergic, noncholinergic nerve components in the autonomic nervous system is now well established. They are strongly represented in the gastrointestinal tract of all vertebrates and have been identified in a variety of other organs, including lung, trachea, bladder, esophagus, eye, seminal vesicles, and possibly parts of the vascular and central nervous systems. Their ultrastructural identification and transmission properties are known and their physiological role is beginning to be understood, at least in the gastrointestinal tract. Evidence that ATP is the transmitter released from nonadrenergic, noncholinergic (purinergic) nerves includes: (a) synthesis and storage of ATP in nerves; (b) release of ATP from the nerves when they are stimulated; (c) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (d) the presence of Mg-activated ATPase, 5'nucleotidase, and adenosine deaminase, enzymes, which inactivate ATP; (e) drugs (including 2-substituted imidazolines, 2,2'-pyridylisatogen and dipyridamole), that produce similar blocking or potentiating effects on the response to exogenously applied atp and nerve stimulation.", "contents": "Purine nucleotides. The existence of nonadrenergic, noncholinergic nerve components in the autonomic nervous system is now well established. They are strongly represented in the gastrointestinal tract of all vertebrates and have been identified in a variety of other organs, including lung, trachea, bladder, esophagus, eye, seminal vesicles, and possibly parts of the vascular and central nervous systems. Their ultrastructural identification and transmission properties are known and their physiological role is beginning to be understood, at least in the gastrointestinal tract. Evidence that ATP is the transmitter released from nonadrenergic, noncholinergic (purinergic) nerves includes: (a) synthesis and storage of ATP in nerves; (b) release of ATP from the nerves when they are stimulated; (c) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (d) the presence of Mg-activated ATPase, 5'nucleotidase, and adenosine deaminase, enzymes, which inactivate ATP; (e) drugs (including 2-substituted imidazolines, 2,2'-pyridylisatogen and dipyridamole), that produce similar blocking or potentiating effects on the response to exogenously applied atp and nerve stimulation."}
{"id": "PMID:15419", "title": "Glucocorticoid regulation of the serotonergic system of the brain.", "content": "Glucorticoids at concentrations above 10(-7) M stimulate the uptake of tryptophan by brain synaptosomes. Furthermore, in both developmental and drug-induced (reserpine and ethanol) increases of brain tryptophan hydroxylase activity, glucocorticoids are required in order for the increases to occur. If de novo enzyme synthesis is assumed to take place in such increases, we could adopt the working hypothesis that two loci of glucocorticoid action may exist in serotonergic neurons with respect to their specific function: one in the cell body presumably in a sequence of macromolecular events, and the other directly on nerve terminals. Thus, in its immediate action, the hormone may rapidly regulate 5-HT synthesis through an increased uptake of tryptophan by nerve terminals. In the slow action, the hormone may mainly play a permissive role in the induction of tryptophan hydroxylase by factors yet to be identified.", "contents": "Glucocorticoid regulation of the serotonergic system of the brain. Glucorticoids at concentrations above 10(-7) M stimulate the uptake of tryptophan by brain synaptosomes. Furthermore, in both developmental and drug-induced (reserpine and ethanol) increases of brain tryptophan hydroxylase activity, glucocorticoids are required in order for the increases to occur. If de novo enzyme synthesis is assumed to take place in such increases, we could adopt the working hypothesis that two loci of glucocorticoid action may exist in serotonergic neurons with respect to their specific function: one in the cell body presumably in a sequence of macromolecular events, and the other directly on nerve terminals. Thus, in its immediate action, the hormone may rapidly regulate 5-HT synthesis through an increased uptake of tryptophan by nerve terminals. In the slow action, the hormone may mainly play a permissive role in the induction of tryptophan hydroxylase by factors yet to be identified."}
{"id": "PMID:15421", "title": "A neurobiological role for a protein activator of cyclic nucleotide phosphodiesterase.", "content": "This work supports the idea that PDEA is bound and stored in brain particulate fraction. The release of PDEA into cytosol where the activator-sensitive PDE is located, is the first event in the process of the regulation of cAMP metabolism and inactivation. PDEA is released by cAMP-dependent phosphorylation of the activator-binding sites. This process is Ca2+ independent and does not occur in the presence of cGMP and cGMP-dependent phosphorylation. The free, soluble PDEA activates the high Km PDE in the presence of micromolar concentrations of Ca2+. This protein decreases severalfold the Km for cAMP of the high Km activator-sensitive PDE. PDEA regulates cAMP metabolism when the concentration of cAMP is elevated by a transsynaptic activation of adenylate cyclase. The rate of synthesis and the release of PDEA might be a part of the process of receptor sub- and supersensitivity, which has been reported during denervation or as a result of chronic treatment with drugs.", "contents": "A neurobiological role for a protein activator of cyclic nucleotide phosphodiesterase. This work supports the idea that PDEA is bound and stored in brain particulate fraction. The release of PDEA into cytosol where the activator-sensitive PDE is located, is the first event in the process of the regulation of cAMP metabolism and inactivation. PDEA is released by cAMP-dependent phosphorylation of the activator-binding sites. This process is Ca2+ independent and does not occur in the presence of cGMP and cGMP-dependent phosphorylation. The free, soluble PDEA activates the high Km PDE in the presence of micromolar concentrations of Ca2+. This protein decreases severalfold the Km for cAMP of the high Km activator-sensitive PDE. PDEA regulates cAMP metabolism when the concentration of cAMP is elevated by a transsynaptic activation of adenylate cyclase. The rate of synthesis and the release of PDEA might be a part of the process of receptor sub- and supersensitivity, which has been reported during denervation or as a result of chronic treatment with drugs."}
{"id": "PMID:15422", "title": "Cellular depolarization and cyclic nucleotide content in central nervous system.", "content": "There is ample evidence indicating that cAMP and cGMP content in mamalian brain is markedly influenced by cellular depolarization. The relationships between the two cyclic nucleotides and the complex process of cellular depolarization, which in turn leads to extensive functional and metabolic consequences are incompletely understood, however. Much data, which are reviewed in the present chapter, suggest that cellular depolarization leads to elevation of cAMP and cGMP levels by two different and unrelated mechanisms. With regard to cAMP, it seems reasonable to conclude that cellular depolarization in CNS causes a release of adenosine, and it is the subsequent action of this substance which accounts for a portion of the elevation of cAMP levels. At present, one cannot ascertain whether or not other factors contribute to the increase of cAMP content resulting from cellular depolarization. It is probable that it is not cellular depolarization, per se, but the influx of Ca2+ into intracellular spaces caused by cellular depolarization which increases the content of cGMP. The specific effects of Ca2+, Mg2+, and other divalent cations on the cGMP response suggest a close relationship between the cyclic nucleotide and some process associated with release of one or more yet undefined neurotransmitters. Wether the involvement is in presynaptic or postsynaptic mechanisms also remains to be determined.", "contents": "Cellular depolarization and cyclic nucleotide content in central nervous system. There is ample evidence indicating that cAMP and cGMP content in mamalian brain is markedly influenced by cellular depolarization. The relationships between the two cyclic nucleotides and the complex process of cellular depolarization, which in turn leads to extensive functional and metabolic consequences are incompletely understood, however. Much data, which are reviewed in the present chapter, suggest that cellular depolarization leads to elevation of cAMP and cGMP levels by two different and unrelated mechanisms. With regard to cAMP, it seems reasonable to conclude that cellular depolarization in CNS causes a release of adenosine, and it is the subsequent action of this substance which accounts for a portion of the elevation of cAMP levels. At present, one cannot ascertain whether or not other factors contribute to the increase of cAMP content resulting from cellular depolarization. It is probable that it is not cellular depolarization, per se, but the influx of Ca2+ into intracellular spaces caused by cellular depolarization which increases the content of cGMP. The specific effects of Ca2+, Mg2+, and other divalent cations on the cGMP response suggest a close relationship between the cyclic nucleotide and some process associated with release of one or more yet undefined neurotransmitters. Wether the involvement is in presynaptic or postsynaptic mechanisms also remains to be determined."}
{"id": "PMID:15426", "title": "Long-term regulatory mechanisms for tyrosine hydroxylase in sympathetic ganglia and carotid body.", "content": "The delayed activation of TH elicited by hypoxia in carotid body indirectly suggests that the release of dopamine is part of the responses elicited by hypoxia. The TH activation appears to be independent from nicotinic receptor stimulation and can be abolished by dopaminergic receptor stimulation. Dexamethasone also increases the activity of TH. Since both hypoxia and dexamethasone fail to change the kinetic constants, the long-term increase of TH could be viewed as an expression of new synthesis of enzyme molecules. This assumption is supported by the evidence presented on the prompt kinetic change in PDE, which according to the model proposed by Uzunov et al. (42) expresses the participation of a prompt and sustained response of the second messenger in postsynaptic cells. It remains to be ascertained whether the change in the catalytic activity of PDE which metabolizes the second messenger can be suppressed by dopamine-receptor blockers. Immediate changes of PDE coupled with the delayed increase in TH activity may contribute to a better understanding of the neuronal mechanisms controlling the chemoreceptor function. It is hoped that the continuation of these studies will help to define the function of type I cells in the carotid body.", "contents": "Long-term regulatory mechanisms for tyrosine hydroxylase in sympathetic ganglia and carotid body. The delayed activation of TH elicited by hypoxia in carotid body indirectly suggests that the release of dopamine is part of the responses elicited by hypoxia. The TH activation appears to be independent from nicotinic receptor stimulation and can be abolished by dopaminergic receptor stimulation. Dexamethasone also increases the activity of TH. Since both hypoxia and dexamethasone fail to change the kinetic constants, the long-term increase of TH could be viewed as an expression of new synthesis of enzyme molecules. This assumption is supported by the evidence presented on the prompt kinetic change in PDE, which according to the model proposed by Uzunov et al. (42) expresses the participation of a prompt and sustained response of the second messenger in postsynaptic cells. It remains to be ascertained whether the change in the catalytic activity of PDE which metabolizes the second messenger can be suppressed by dopamine-receptor blockers. Immediate changes of PDE coupled with the delayed increase in TH activity may contribute to a better understanding of the neuronal mechanisms controlling the chemoreceptor function. It is hoped that the continuation of these studies will help to define the function of type I cells in the carotid body."}
{"id": "PMID:15427", "title": "[Sexual development of boys, treated surgically for dystopia of testicles (author's transl)].", "content": "A clinical follow-up examination was made in a group of 208 children and adolescents who had undergone surgical treatment for congenital cryptorchid testis (unilateral or bilateral) between 2 and 10 years before. The puberal growth and maturing process of the primary and secondary sex characteristics of this morbidity group was compared to that of normal juveniles. The examination was made according to clinical criteria: length and circumference of the penis, volume of testes, general development of the genitals, pubic hair. Compared to normal juveniles, the genital development of the children and adolescents of the follow-up examinations series was retarded.", "contents": "[Sexual development of boys, treated surgically for dystopia of testicles (author's transl)]. A clinical follow-up examination was made in a group of 208 children and adolescents who had undergone surgical treatment for congenital cryptorchid testis (unilateral or bilateral) between 2 and 10 years before. The puberal growth and maturing process of the primary and secondary sex characteristics of this morbidity group was compared to that of normal juveniles. The examination was made according to clinical criteria: length and circumference of the penis, volume of testes, general development of the genitals, pubic hair. Compared to normal juveniles, the genital development of the children and adolescents of the follow-up examinations series was retarded."}
{"id": "PMID:15432", "title": "Study of the priming effect of interferon in L cells. II. Metabolic requirements for the development of primed state.", "content": "Actinomycin D at a concentration inhibitory for nucleolar RNA synthesis did not influence the development of priming. Higher concentrations of the drug and long-term alpha-amanitin or cycloheximide pretreatments, inhibitory for heterogenous nuclear RNA synthesis, prevented the establishment of the primed state. The inhibition of mitochondrial DNA and protein synthesis did not inhibit the priming effect of interferon. Attempts to prime cells with pretreatments other than interferon were not successful.", "contents": "Study of the priming effect of interferon in L cells. II. Metabolic requirements for the development of primed state. Actinomycin D at a concentration inhibitory for nucleolar RNA synthesis did not influence the development of priming. Higher concentrations of the drug and long-term alpha-amanitin or cycloheximide pretreatments, inhibitory for heterogenous nuclear RNA synthesis, prevented the establishment of the primed state. The inhibition of mitochondrial DNA and protein synthesis did not inhibit the priming effect of interferon. Attempts to prime cells with pretreatments other than interferon were not successful."}
{"id": "PMID:15433", "title": "Influence of polypeptide molecular and side chain lengths and of side chain steric location on the kinetics of basic polypeptide-induced sensitization of primate cells to transfection.", "content": "Kinetics of sensitization of chimpanzee cell sheets to transfection by poliovirus RNA was determined for 5 basic polypeptides. With basic olypeptide hydrobromide at 100 microng/ml, initial sensitization rate was faster for poly-L-ornithine of average molecular weight (AMW) 15500 than of AMW 105000, and much faster for poly-L-lysine of AMW 1700 than of AMW 140000. Desensitization phases were observed with the 2 shorter polypeptides. Sensitization was much faster and sensitivity maxima were considerably higher for the polyornithines than for the polylysines. Poly-D-lysine of AMW 160000 sensitized cells slightly faster than poly-L-lysine of AMW 140000, but gave about the same sensitivity maximum. Analysis of the slow cell sensitization by poly-L-lysine of AMW 140000 revealed 2 steps: a fast step 1 (attachment) and a slow step 2 (processing).", "contents": "Influence of polypeptide molecular and side chain lengths and of side chain steric location on the kinetics of basic polypeptide-induced sensitization of primate cells to transfection. Kinetics of sensitization of chimpanzee cell sheets to transfection by poliovirus RNA was determined for 5 basic polypeptides. With basic olypeptide hydrobromide at 100 microng/ml, initial sensitization rate was faster for poly-L-ornithine of average molecular weight (AMW) 15500 than of AMW 105000, and much faster for poly-L-lysine of AMW 1700 than of AMW 140000. Desensitization phases were observed with the 2 shorter polypeptides. Sensitization was much faster and sensitivity maxima were considerably higher for the polyornithines than for the polylysines. Poly-D-lysine of AMW 160000 sensitized cells slightly faster than poly-L-lysine of AMW 140000, but gave about the same sensitivity maximum. Analysis of the slow cell sensitization by poly-L-lysine of AMW 140000 revealed 2 steps: a fast step 1 (attachment) and a slow step 2 (processing)."}
{"id": "PMID:15434", "title": "Susceptibility of various cell lines to virulent an attenuated strains of pseudorabies virus at supraoptimal temperature.", "content": "Replication of virulent and attenuated strains of pseudorabies virus (PRV) at supraoptimal temperature was studied in rabbit lung (ZP), pig kidney (PS), and BHK-21 cells adapted and non-adapted to 40 degrees C and L, HeLa and human amniotic (Am) cells non-adapted to 40 degrees C. The temperature of 40 degreeC did not influence the type cytopathic effect (CPE) in either adapted or non-adapted cells. According to the susceptibility at 40 degrees C the cells could be divided into three groups: cells permissive for all PRV strains (adapted and non-adapted ZP and non-adapted BHK-21 and PS); cells non-permissive for all PRV strains (L, HeLa and Am); and cells permissive for virulent and non-permissive for attenuated PRV strains (adapted BHK-21 and PS). The virus titres in permissive cells at 40 degrees C did not differ from those obtained at 37 degrees C. The attenuated strain CK-PRV X was found to be a tsmutant of PRV with host range character.", "contents": "Susceptibility of various cell lines to virulent an attenuated strains of pseudorabies virus at supraoptimal temperature. Replication of virulent and attenuated strains of pseudorabies virus (PRV) at supraoptimal temperature was studied in rabbit lung (ZP), pig kidney (PS), and BHK-21 cells adapted and non-adapted to 40 degrees C and L, HeLa and human amniotic (Am) cells non-adapted to 40 degrees C. The temperature of 40 degreeC did not influence the type cytopathic effect (CPE) in either adapted or non-adapted cells. According to the susceptibility at 40 degrees C the cells could be divided into three groups: cells permissive for all PRV strains (adapted and non-adapted ZP and non-adapted BHK-21 and PS); cells non-permissive for all PRV strains (L, HeLa and Am); and cells permissive for virulent and non-permissive for attenuated PRV strains (adapted BHK-21 and PS). The virus titres in permissive cells at 40 degrees C did not differ from those obtained at 37 degrees C. The attenuated strain CK-PRV X was found to be a tsmutant of PRV with host range character."}
{"id": "PMID:15435", "title": "Effect of streptovirudin on parainfluenza 3 virus multiplication.", "content": "Streptovirudin (SV) in a concentration of 100 microng/ml reduced the multiplication of parainfluenza 3 virus by about 3.5 log units. When uninfected WISH cells were treated for 2 and 12 hours with 100 mug/ml of SV, 3H-thymidineincorporation was decreased, but no marked differences were observed in the incorporation of 3H-uridine. The level of intracellular cyclic adenosine monophosphate (c-AMP) was found to decrease in SV-treated cells.", "contents": "Effect of streptovirudin on parainfluenza 3 virus multiplication. Streptovirudin (SV) in a concentration of 100 microng/ml reduced the multiplication of parainfluenza 3 virus by about 3.5 log units. When uninfected WISH cells were treated for 2 and 12 hours with 100 mug/ml of SV, 3H-thymidineincorporation was decreased, but no marked differences were observed in the incorporation of 3H-uridine. The level of intracellular cyclic adenosine monophosphate (c-AMP) was found to decrease in SV-treated cells."}
{"id": "PMID:15436", "title": "Sunday Canyon virus, a new ungrouped agent from the tick Argas (A.) cooleyi in Texas.", "content": "A new arbovirus was isolated from Texas, U.S.A., populations of the Cliff Swallow parasits Argas (Argas) cooleyi Kohls and Hoogstraal, 1960. The virus, named Sunday Canyon, is serological urelated to any of 185 arbovirus strains or 20 other viral agents with which it was compared. Morphologically it resembles Bunyamwera viruses and, in common with them, is sensitive to lipid solvents and acid pH, and apparently possesses RNA. Although considerably resistant to a temperature of 41.5 degrees C, it rapidly loses infectivity when incubated at 56 degrees C. It is lethal for newborn white mice and infective for the Vero and Antheraea eucalypti cell lines. Sundays Canyon virus is the second tick-associated, Bunyamwera virus-like agent known from North America and the third virus to be reported from A. cooleyi in Texas.", "contents": "Sunday Canyon virus, a new ungrouped agent from the tick Argas (A.) cooleyi in Texas. A new arbovirus was isolated from Texas, U.S.A., populations of the Cliff Swallow parasits Argas (Argas) cooleyi Kohls and Hoogstraal, 1960. The virus, named Sunday Canyon, is serological urelated to any of 185 arbovirus strains or 20 other viral agents with which it was compared. Morphologically it resembles Bunyamwera viruses and, in common with them, is sensitive to lipid solvents and acid pH, and apparently possesses RNA. Although considerably resistant to a temperature of 41.5 degrees C, it rapidly loses infectivity when incubated at 56 degrees C. It is lethal for newborn white mice and infective for the Vero and Antheraea eucalypti cell lines. Sundays Canyon virus is the second tick-associated, Bunyamwera virus-like agent known from North America and the third virus to be reported from A. cooleyi in Texas."}
{"id": "PMID:15437", "title": "Appearance and some unusual features of Epstein-Barr virus antibody production in infectious mononucleosis and other health disorders.", "content": "The indirect immunofluorescence (IF) test and the complement-fixation reaction (CFR) were used in examination of over 1500 sera obtained from patients with infectious mononucleosis (IM) and other health disorders. The evidence obtained supports a direct aetiological relationship between Epstein-Barr virus (EBV) and IM and points on a relationship of EBV to some other lymphadenopathies and health disorders. The incidence of the IgG type antibody against virus capsid antigen (EB-VCA) and soluble antigen (CF-SA) obtained from EBV genome-positive cells among different age groups of patients is described along with results of long-term examinations of serum samples from IM patients. The appearance and dynamics of production of both types of EBV antibody and their persistence in the organism varied. Long-lasting oscillations, in particular of the EB-VCA antibody levels were found in sera of patients with prolonged health disorders following IM. The diagnosis value of the IF test and the CFR is discussed.", "contents": "Appearance and some unusual features of Epstein-Barr virus antibody production in infectious mononucleosis and other health disorders. The indirect immunofluorescence (IF) test and the complement-fixation reaction (CFR) were used in examination of over 1500 sera obtained from patients with infectious mononucleosis (IM) and other health disorders. The evidence obtained supports a direct aetiological relationship between Epstein-Barr virus (EBV) and IM and points on a relationship of EBV to some other lymphadenopathies and health disorders. The incidence of the IgG type antibody against virus capsid antigen (EB-VCA) and soluble antigen (CF-SA) obtained from EBV genome-positive cells among different age groups of patients is described along with results of long-term examinations of serum samples from IM patients. The appearance and dynamics of production of both types of EBV antibody and their persistence in the organism varied. Long-lasting oscillations, in particular of the EB-VCA antibody levels were found in sera of patients with prolonged health disorders following IM. The diagnosis value of the IF test and the CFR is discussed."}
{"id": "PMID:15438", "title": "Characteristics of poliovirus type 3 strains after passage through monkey central nervous system.", "content": "Cercopithecus aethiops monkeys were inoculated intracerebrally with Sabin's type 3 polivoirus strain, and with strains isolated from subjects vaccinated with Leon 12a1b and from their contacts. Sample of brain, spinal cord, kidneys, lymph nodes, blood and spinal fluid were taken. From these materials, (except of kidneys) 23 poliovirus strains of type 3 were isolated. Genetic markers rct 40.3, rct 41, d and IST were determined for these strains. The changes observed in genetic markers of strains passaged through the cental nervous system (CNS) of monkeys are described.", "contents": "Characteristics of poliovirus type 3 strains after passage through monkey central nervous system. Cercopithecus aethiops monkeys were inoculated intracerebrally with Sabin's type 3 polivoirus strain, and with strains isolated from subjects vaccinated with Leon 12a1b and from their contacts. Sample of brain, spinal cord, kidneys, lymph nodes, blood and spinal fluid were taken. From these materials, (except of kidneys) 23 poliovirus strains of type 3 were isolated. Genetic markers rct 40.3, rct 41, d and IST were determined for these strains. The changes observed in genetic markers of strains passaged through the cental nervous system (CNS) of monkeys are described."}
{"id": "PMID:15439", "title": "6-MFA, an antiviral agent from Aspergillus ochraceus ATCC 28706: influence of body weight and mineral oil administration of the antiviral activity in mice.", "content": "Sera obtained from mice treated with 6-MFA, an antiviral agent from Aspergillus ochraceus ATCC 28706 showing high interferon activity, could be transferred to healthy animals to make them resistant to Semliki Forest Virus (SFV) infection. Body weight of mice directly influenced, within limits, the proportion of treated mice surviving challenge virus infection as well as interferon production. Mineral oil (liquid paraffin, B. P.) administered prior to 6-MFA increased both the level of interferon in serum and the protection rate of the treated animals.", "contents": "6-MFA, an antiviral agent from Aspergillus ochraceus ATCC 28706: influence of body weight and mineral oil administration of the antiviral activity in mice. Sera obtained from mice treated with 6-MFA, an antiviral agent from Aspergillus ochraceus ATCC 28706 showing high interferon activity, could be transferred to healthy animals to make them resistant to Semliki Forest Virus (SFV) infection. Body weight of mice directly influenced, within limits, the proportion of treated mice surviving challenge virus infection as well as interferon production. Mineral oil (liquid paraffin, B. P.) administered prior to 6-MFA increased both the level of interferon in serum and the protection rate of the treated animals."}
{"id": "PMID:15440", "title": "Disintegration of red clover mottle virus virions under different conditions of storage in vitro.", "content": "Red clover mottle virus was kept in 0.1 M phosphate buffer, pH 7.0, at 4, --20 and --60 degrees C for 1 and 4 weeks and 3 months. The degree of virion disintegration was the highest at --20 degrees C and the lowest at 4 degrees C. Two cycles of freezing and thawing destroyed the virions. In frozen samples (at both --20 and --60 degrees C), the nucleoprotein sedimentation component M was disintegrated more than component B.", "contents": "Disintegration of red clover mottle virus virions under different conditions of storage in vitro. Red clover mottle virus was kept in 0.1 M phosphate buffer, pH 7.0, at 4, --20 and --60 degrees C for 1 and 4 weeks and 3 months. The degree of virion disintegration was the highest at --20 degrees C and the lowest at 4 degrees C. Two cycles of freezing and thawing destroyed the virions. In frozen samples (at both --20 and --60 degrees C), the nucleoprotein sedimentation component M was disintegrated more than component B."}
{"id": "PMID:15441", "title": "Effect of a proteolytic enzyme inhbitor on influenza virus replication.", "content": "N-tosyl-L-phenylalanyl chloromethane patially inhibited the multiplicatiion of fowl plague virus (FPV) in infected cells. The capacity of the inhibitor to suppress the muliplication of FPV depended on the host cell system.", "contents": "Effect of a proteolytic enzyme inhbitor on influenza virus replication. N-tosyl-L-phenylalanyl chloromethane patially inhibited the multiplicatiion of fowl plague virus (FPV) in infected cells. The capacity of the inhibitor to suppress the muliplication of FPV depended on the host cell system."}
{"id": "PMID:15442", "title": "Structure of inclusion bodies of cabbage black ring virus.", "content": "Inclusions in cells of Nicotiana glutinosa infected with a horse-radish strain of cabbage black ring virus (CBRV) were investigated on ultrathin sections. Large amorphous inclusions contained cellular constitutents showing usually no pathological alterations. Lamellar inclusions (bundles, circular inclusions, pinwheels), closely associated with endoplasmic reticulum, occurred frequently in areas of cytoplasm showing no vesiculation. Sac-like structures composed of concentric lamellae were observed in the cytoplasm or intruding into the vacuole. Spherosomes containing each a single crystal were found very often in the cytoplasm. Masses of virus particles in a parallel arrangement were usually located at the tonoplast.", "contents": "Structure of inclusion bodies of cabbage black ring virus. Inclusions in cells of Nicotiana glutinosa infected with a horse-radish strain of cabbage black ring virus (CBRV) were investigated on ultrathin sections. Large amorphous inclusions contained cellular constitutents showing usually no pathological alterations. Lamellar inclusions (bundles, circular inclusions, pinwheels), closely associated with endoplasmic reticulum, occurred frequently in areas of cytoplasm showing no vesiculation. Sac-like structures composed of concentric lamellae were observed in the cytoplasm or intruding into the vacuole. Spherosomes containing each a single crystal were found very often in the cytoplasm. Masses of virus particles in a parallel arrangement were usually located at the tonoplast."}
{"id": "PMID:15443", "title": "An iridovirus from larvae of Culiseta annulata and Culex territans.", "content": "Field-collected 4th instar larvae of Culiseta annulata and Culex territans were found to be infected with mosquito iridescent virus (MIV). Ultrathin sections revealed the presence in infected cells of different types of immature virus particles of an average diameter of 180 and 190 nm respectively.", "contents": "An iridovirus from larvae of Culiseta annulata and Culex territans. Field-collected 4th instar larvae of Culiseta annulata and Culex territans were found to be infected with mosquito iridescent virus (MIV). Ultrathin sections revealed the presence in infected cells of different types of immature virus particles of an average diameter of 180 and 190 nm respectively."}
{"id": "PMID:15447", "title": "Psychological aspects of cardiac arrhythmia.", "content": "A review of data from a wide spectrum of research studies suggests that psychological-emotional factors can significantly influence and alter the incidence of cardiac arrhythmia. While the existing data are, in many cases, difficult to interpret because of theoretical and methodological problems, sufficient evidence does exist to warrant a concerted investigation into the total involvement of psychological factors in cardiac arrhythmia.", "contents": "Psychological aspects of cardiac arrhythmia. A review of data from a wide spectrum of research studies suggests that psychological-emotional factors can significantly influence and alter the incidence of cardiac arrhythmia. While the existing data are, in many cases, difficult to interpret because of theoretical and methodological problems, sufficient evidence does exist to warrant a concerted investigation into the total involvement of psychological factors in cardiac arrhythmia."}
{"id": "PMID:15448", "title": "Internal mammary artery graft for ischemic heart disease. Effect of revascularization on clinical status and survival.", "content": "Four hundred consecutive patients, 80 percent of whom had multiple vessel obstruction, received a single internal mammary artery graft (121 patients) alone or combined with vein grafts (279 patients) in 1971 and 1972. Four patients died during or within 30 days of the operation. Sixteen patients had intraoperative infarction; three died. Arteriography was performed postoperatively (mean 12 months) in 254 patients, and 248 of 261 internal mammary artery grafts (95 percent) and 195 of 237 vein grafts (82 percent) were patent. Follow-up was complete (mean interval 38 months); all 80 patients with single vessel disease are alive, and the 3 year survival rate for patients with double and triple vessel disease was 98.7 and 94.4 percent, respectively. Comparison of longevity of 741 patients who had received vein grafts in 1967 to 1970 with that of 400 patients with internal mammary artery grafts (1971 to 1972) indicates greater survival for the recent series (P less than 0.004). Factors responsible for improved survival include (1) reduced operative mortality, (2) fewer intraoperative infarctions, (3) more complete revascularization, and (4) higher patency rate of the internal mammary artery graft.", "contents": "Internal mammary artery graft for ischemic heart disease. Effect of revascularization on clinical status and survival. Four hundred consecutive patients, 80 percent of whom had multiple vessel obstruction, received a single internal mammary artery graft (121 patients) alone or combined with vein grafts (279 patients) in 1971 and 1972. Four patients died during or within 30 days of the operation. Sixteen patients had intraoperative infarction; three died. Arteriography was performed postoperatively (mean 12 months) in 254 patients, and 248 of 261 internal mammary artery grafts (95 percent) and 195 of 237 vein grafts (82 percent) were patent. Follow-up was complete (mean interval 38 months); all 80 patients with single vessel disease are alive, and the 3 year survival rate for patients with double and triple vessel disease was 98.7 and 94.4 percent, respectively. Comparison of longevity of 741 patients who had received vein grafts in 1967 to 1970 with that of 400 patients with internal mammary artery grafts (1971 to 1972) indicates greater survival for the recent series (P less than 0.004). Factors responsible for improved survival include (1) reduced operative mortality, (2) fewer intraoperative infarctions, (3) more complete revascularization, and (4) higher patency rate of the internal mammary artery graft."}
{"id": "PMID:15449", "title": "Enkephalin, drug addiction and acupuncture.", "content": "From the results of clinical and basic research, there is clear evidence that acupuncture analgesia is closely associated with the nervous system, especially the central nervous system. Stimulation of certain acupuncture loci which have been used for analgesia during operations also can calm the withdrawal symptoms of morphine and heroin addicts. Acupuncture analgesia can be antagonized by the specific narcotic antagonist, naloxone. These findings suggest the factor or factors produced by acupuncture stimulation would also have agonist activity on opiate receptors. Moreover, the morphine receptors are most concentrated in those parts of the brain concerned with perception of pain and the pathway of acupuncture stimulation. Since the opiate receptors are associated with the synaptic fraction of brain cell membrane preparations, the natural ligand of these receptors may be a neurotransmitter. Enkephalin has stronger binding affinity to opiate receptors than morphine, which suggests that it is the natural ligand for these receptors. In other words, enkephalin might be the natural \"pain killer\" produced in the brain to suppress pain. If we summate all the information available now, it is possible to suggest that enkephalin may be the product of the nervous system released by acupuncture stimulation to create an analgesic effect as well as suppress opiate withdrawal symptoms.", "contents": "Enkephalin, drug addiction and acupuncture. From the results of clinical and basic research, there is clear evidence that acupuncture analgesia is closely associated with the nervous system, especially the central nervous system. Stimulation of certain acupuncture loci which have been used for analgesia during operations also can calm the withdrawal symptoms of morphine and heroin addicts. Acupuncture analgesia can be antagonized by the specific narcotic antagonist, naloxone. These findings suggest the factor or factors produced by acupuncture stimulation would also have agonist activity on opiate receptors. Moreover, the morphine receptors are most concentrated in those parts of the brain concerned with perception of pain and the pathway of acupuncture stimulation. Since the opiate receptors are associated with the synaptic fraction of brain cell membrane preparations, the natural ligand of these receptors may be a neurotransmitter. Enkephalin has stronger binding affinity to opiate receptors than morphine, which suggests that it is the natural ligand for these receptors. In other words, enkephalin might be the natural \"pain killer\" produced in the brain to suppress pain. If we summate all the information available now, it is possible to suggest that enkephalin may be the product of the nervous system released by acupuncture stimulation to create an analgesic effect as well as suppress opiate withdrawal symptoms."}
{"id": "PMID:15450", "title": "The Silver-Russel syndrome: a case with sexual ambiguity, and a review of literature.", "content": "A 38-month-old patient with Silver-Russel syndrome (SRS) and ambiguous genitalia had a 46,XY karyotype on leukocyte and fibroblast cultures. This is the third SRS child with ambiguous genitalia described in the literature. In a review of the findings in 148 reported cases of the syndrome, abnormalities occurring in over 50% of the cases are short stature, craniofacial dysproportion, low birth weight, term gestation, body asymmetry, incurved fifth digits, normal intelligence, short fifth digits, and down-curved corners of the mouth (shark mouth).", "contents": "The Silver-Russel syndrome: a case with sexual ambiguity, and a review of literature. A 38-month-old patient with Silver-Russel syndrome (SRS) and ambiguous genitalia had a 46,XY karyotype on leukocyte and fibroblast cultures. This is the third SRS child with ambiguous genitalia described in the literature. In a review of the findings in 148 reported cases of the syndrome, abnormalities occurring in over 50% of the cases are short stature, craniofacial dysproportion, low birth weight, term gestation, body asymmetry, incurved fifth digits, normal intelligence, short fifth digits, and down-curved corners of the mouth (shark mouth)."}
{"id": "PMID:15451", "title": "Detection of heterozygotes for tyrosinase-negative oculocutaneous albinism by hairbulb tyrosinase assay.", "content": "Five heterozygotes for ty-neg OCA had absent or markedly reduced hairbulb tyrosinase activity, when compared to normally pigmented control subjects. Clinically, all five were fully pigmented and could not be distinguished from the normal control subjects. It is proposed that the quantitative hairbulb tyrosinase assay can be used to detect heterozygotes for ty-neg OCA. A mechanism to explain the low levels of activity in the hairbulbs from heterozygotes is discussed.", "contents": "Detection of heterozygotes for tyrosinase-negative oculocutaneous albinism by hairbulb tyrosinase assay. Five heterozygotes for ty-neg OCA had absent or markedly reduced hairbulb tyrosinase activity, when compared to normally pigmented control subjects. Clinically, all five were fully pigmented and could not be distinguished from the normal control subjects. It is proposed that the quantitative hairbulb tyrosinase assay can be used to detect heterozygotes for ty-neg OCA. A mechanism to explain the low levels of activity in the hairbulbs from heterozygotes is discussed."}
{"id": "PMID:15452", "title": "Very low arylsulfatase A and cerebroside sulfatase activities in leukocytes of healthy members of metachromatic leukodystrophy family.", "content": "Very low levels of arylsulfatase A (ASA) have been found in the leukocytes of healthy members of a metachromatic leukodystrophy (MLD) family. The cerebroside sulfate sulfatase (CSS) activities in the same individuals are about 10% of the control level. Arguments favoring a dominant mutation different from that of classical MLD are presented. This report reinforces the relationship between the two enzymatic activities.", "contents": "Very low arylsulfatase A and cerebroside sulfatase activities in leukocytes of healthy members of metachromatic leukodystrophy family. Very low levels of arylsulfatase A (ASA) have been found in the leukocytes of healthy members of a metachromatic leukodystrophy (MLD) family. The cerebroside sulfate sulfatase (CSS) activities in the same individuals are about 10% of the control level. Arguments favoring a dominant mutation different from that of classical MLD are presented. This report reinforces the relationship between the two enzymatic activities."}
{"id": "PMID:15456", "title": "Factors determining human chorion laeve permeability in vitro.", "content": "An increased mean diffusion permeability across human chorion laeve in vitro was measured for meperidine (D = 5.26 x 10(-6) cm.2 sec.-1) and diazepam (D = 4.51 X 10(-6) cm.2 sec.-1). These values corresponded to large chloroform-buffer partition coefficients (49 and 29) measured for these two compounds. Diffusion permeability values of 3.98 and 2.18 x 10-6 cm.2 sec.-1 measured for urea and glucose corresponded to their relative insolubility in lipid, as indicated by chloroform-buffer partition coefficients of 0.05 and 0.0004, respectively. An increase in placental permeability in vitro to the weak organic acid 5,5-dimethyl, 2,4-oxazalidinedione at lower pH's corresponded to an increase in the fat-soluble nonionized fraction of this compound. These data support the concept that this tissue is most permeable to compounds of relatively small molecular size and/or with a high level of lipid solubility. The large diffusion permeability values measured for meperidine and diazepam suggest that these compounds will diffuse rapidly between mother and fetus at a maximal rate limited only by uterine blood flow.", "contents": "Factors determining human chorion laeve permeability in vitro. An increased mean diffusion permeability across human chorion laeve in vitro was measured for meperidine (D = 5.26 x 10(-6) cm.2 sec.-1) and diazepam (D = 4.51 X 10(-6) cm.2 sec.-1). These values corresponded to large chloroform-buffer partition coefficients (49 and 29) measured for these two compounds. Diffusion permeability values of 3.98 and 2.18 x 10-6 cm.2 sec.-1 measured for urea and glucose corresponded to their relative insolubility in lipid, as indicated by chloroform-buffer partition coefficients of 0.05 and 0.0004, respectively. An increase in placental permeability in vitro to the weak organic acid 5,5-dimethyl, 2,4-oxazalidinedione at lower pH's corresponded to an increase in the fat-soluble nonionized fraction of this compound. These data support the concept that this tissue is most permeable to compounds of relatively small molecular size and/or with a high level of lipid solubility. The large diffusion permeability values measured for meperidine and diazepam suggest that these compounds will diffuse rapidly between mother and fetus at a maximal rate limited only by uterine blood flow."}
{"id": "PMID:15457", "title": "Effects of calcium on renin and aldosterone in the rat.", "content": "CaCl2 suppresses the plasma renin activity (PRA) response to Na+ deprivation in the rat. The purpose of the present study is:1) to determine if the effect of Ca2+ on PRA is modified by the anion delivered with Ca2+, and 2) to evaluate the effect of Ca2+ loading on aldosterone production. PRA and in vitro aldosterone production by adrenal quarters were measured after a 7-day balance study. On a low Na+ diet, PRA of animals drinking 1% CaCl2 (13.1 ng/ml per h +/- 1.3 SE), but not of animals drinking 1% calcium gluconate, was suppressed (P less than 0.05) compared to that of water-drinking controls (20.9 ng/ml per h +/- 2.1 SE). Aldosterone production of calcium gluconate and CaCl2-loaded animals was greater than that of controls (P less than 0.01). K+ balance of CaCl2 and calcium gluconate-drinking animals was more positive than that of controls (P less than 0.05). In conclusion, inhibition of PRA by CaCl2 but not by calcium gluconate indicates that the effect of Ca2+ on PRA is modified by the accompanying anion. Both CaCl2 and calcium gluconate stimulate aldosterone production, independent of changes in PRA, possibly due to an effect of Ca2+ on K+ balance.", "contents": "Effects of calcium on renin and aldosterone in the rat. CaCl2 suppresses the plasma renin activity (PRA) response to Na+ deprivation in the rat. The purpose of the present study is:1) to determine if the effect of Ca2+ on PRA is modified by the anion delivered with Ca2+, and 2) to evaluate the effect of Ca2+ loading on aldosterone production. PRA and in vitro aldosterone production by adrenal quarters were measured after a 7-day balance study. On a low Na+ diet, PRA of animals drinking 1% CaCl2 (13.1 ng/ml per h +/- 1.3 SE), but not of animals drinking 1% calcium gluconate, was suppressed (P less than 0.05) compared to that of water-drinking controls (20.9 ng/ml per h +/- 2.1 SE). Aldosterone production of calcium gluconate and CaCl2-loaded animals was greater than that of controls (P less than 0.01). K+ balance of CaCl2 and calcium gluconate-drinking animals was more positive than that of controls (P less than 0.05). In conclusion, inhibition of PRA by CaCl2 but not by calcium gluconate indicates that the effect of Ca2+ on PRA is modified by the accompanying anion. Both CaCl2 and calcium gluconate stimulate aldosterone production, independent of changes in PRA, possibly due to an effect of Ca2+ on K+ balance."}
{"id": "PMID:15454", "title": "Immunopathological aspects of hepatitis type B.", "content": "Tissue samples from 180 unselected necropsy cases of various forms of hepatitis were examined by histopathology and immunofluorescence. The hepatitis forms studied included acute fulminant hepatitis (28 patients), subacute hepatitis (48 patients), acute fatal hepatitis (24 patients), chronic aggressive hepatitis (26 patients), liver cirrhosis (49 patients), and \"minimal\" hepatitis (5 patients). Hepatitis B surface antigen and hepatitis B core antigen were detected in 101 patients (56.1 per cent). In these, lesion-bound immune complexes of hepatitis B surface antigen were found in the liver and extrahepatic locations in 77 patients (76.2 per cent). The latter included activated germinal centers of lymph nodes and spleen, focal hyaline lesions of splenic and renal arterioles, necrotic and/or proliferative lesions of small and medium-sized arteries, and kidney glomeruli with mild proliferative and degenerative lesions. There was an inverse relation of the approximate amounts of hepatitis B surface antigen in the liver and the liver damage, the latter being directly proportional to the amount of HBS Ag immune complexes in the liver and indirectly proportional to their amount in extrahepatic locations and to the severity of lesions at these sites.", "contents": "Immunopathological aspects of hepatitis type B. Tissue samples from 180 unselected necropsy cases of various forms of hepatitis were examined by histopathology and immunofluorescence. The hepatitis forms studied included acute fulminant hepatitis (28 patients), subacute hepatitis (48 patients), acute fatal hepatitis (24 patients), chronic aggressive hepatitis (26 patients), liver cirrhosis (49 patients), and \"minimal\" hepatitis (5 patients). Hepatitis B surface antigen and hepatitis B core antigen were detected in 101 patients (56.1 per cent). In these, lesion-bound immune complexes of hepatitis B surface antigen were found in the liver and extrahepatic locations in 77 patients (76.2 per cent). The latter included activated germinal centers of lymph nodes and spleen, focal hyaline lesions of splenic and renal arterioles, necrotic and/or proliferative lesions of small and medium-sized arteries, and kidney glomeruli with mild proliferative and degenerative lesions. There was an inverse relation of the approximate amounts of hepatitis B surface antigen in the liver and the liver damage, the latter being directly proportional to the amount of HBS Ag immune complexes in the liver and indirectly proportional to their amount in extrahepatic locations and to the severity of lesions at these sites."}
{"id": "PMID:15458", "title": "Metabolic features of isolated rat lung cells. I. Factors controlling glucose utilization.", "content": "Isolated rat lung cell suspensions were prepared by collagenase digestion of the lung stroma. These cells were functionally competent as judged, among other criteria, by their constant rates of oxygen uptake and glucose utilization. An important metabolic feature of these cells is that they display very high glycolytic rates. At least 60% of the glucose utilized was converted to lactate, regardless of the glucose concentration in the medium. The state of reduction of the nicotinamide system, as indicated by the lactate-to-pyruvate ratio, was normal, thus indicating that the high glycolytic fluxes are not related to poor oxygenation of the preparation. Utilization of glucose displayed Michaelis-Menten saturation type kinetics with a Vmax of 331 nmol/10(6) cells per h and an apparent Km of 2.4 mM. These values were not affected by the presence of ouabain (0.1 mM), mannoheptulose (5 mM), or insulin (1 mU/ml), whereas phloridzin produced a drastic inhibition of glucose utilzation showing an apparent Ki of 0.4 mM. The substitution of sodium by K+ or Li+ as the predominant cations in the incubation medium does not alter rates of glucose utilization. Optimal pH for glucose utilization was within the physiological range with a more pronounced inhibitory effect at alkaline pH's. The intracellular concentration glucose was found to be low. This finding, in conjunction with a Q10 (27-37 degrees C) for glucose utilization above 2.0 and the differential effects of D- and L-glucose on production, seems to indicate that a stereospecific glucose transport system exists in lung cells. Several findings point to glucose transport into the lung cells as a probable rate-limiting step for its metabolism:1) the activity of the glycolytic enzymes largely exceeded the observed rate of glucose utilization;2) the decrease in enzyme activity during starvation was not accompanied by a decreased glycolytic flux, suggesting that factors other than enzyme activity, perhaps the supply of fuel, are rate limiting in the overall process of glucose breakdown;3) fructose was able to increase lactate production in the presence of saturating concentrations of glucose. These additive effects of glucose and fructose seem to support the point of view that it is not the glycolytic machinery but the supply of fuel which is rate limiting for glucose utilization by isolated rat lung cells.", "contents": "Metabolic features of isolated rat lung cells. I. Factors controlling glucose utilization. Isolated rat lung cell suspensions were prepared by collagenase digestion of the lung stroma. These cells were functionally competent as judged, among other criteria, by their constant rates of oxygen uptake and glucose utilization. An important metabolic feature of these cells is that they display very high glycolytic rates. At least 60% of the glucose utilized was converted to lactate, regardless of the glucose concentration in the medium. The state of reduction of the nicotinamide system, as indicated by the lactate-to-pyruvate ratio, was normal, thus indicating that the high glycolytic fluxes are not related to poor oxygenation of the preparation. Utilization of glucose displayed Michaelis-Menten saturation type kinetics with a Vmax of 331 nmol/10(6) cells per h and an apparent Km of 2.4 mM. These values were not affected by the presence of ouabain (0.1 mM), mannoheptulose (5 mM), or insulin (1 mU/ml), whereas phloridzin produced a drastic inhibition of glucose utilzation showing an apparent Ki of 0.4 mM. The substitution of sodium by K+ or Li+ as the predominant cations in the incubation medium does not alter rates of glucose utilization. Optimal pH for glucose utilization was within the physiological range with a more pronounced inhibitory effect at alkaline pH's. The intracellular concentration glucose was found to be low. This finding, in conjunction with a Q10 (27-37 degrees C) for glucose utilization above 2.0 and the differential effects of D- and L-glucose on production, seems to indicate that a stereospecific glucose transport system exists in lung cells. Several findings point to glucose transport into the lung cells as a probable rate-limiting step for its metabolism:1) the activity of the glycolytic enzymes largely exceeded the observed rate of glucose utilization;2) the decrease in enzyme activity during starvation was not accompanied by a decreased glycolytic flux, suggesting that factors other than enzyme activity, perhaps the supply of fuel, are rate limiting in the overall process of glucose breakdown;3) fructose was able to increase lactate production in the presence of saturating concentrations of glucose. These additive effects of glucose and fructose seem to support the point of view that it is not the glycolytic machinery but the supply of fuel which is rate limiting for glucose utilization by isolated rat lung cells."}
{"id": "PMID:15459", "title": "Glucose and lactate kinetics in burn shock.", "content": "We studied the glucose and lactate kinetics during burn shock by means of the primed constant infusion of [6-3H]glucose and Na-L-(+)-[U-14C]lactate. We found an early postburn hyperglycemia that was due to an increased rate of appearance (Ra) of glucose. Later, the ability of the tissues to extract glucose became impaired, and the plasma glucose concentration increased even more in spite of the return of Ra of glucose to the control level. The Ra of lactate rose rapidly postburn, whereas the rate of disappearance (Rd) of lactate stayed at the control level for 30 min. Consequently, plasma lactate rose approximately 350%. After 30 min, Rd of lactate increased to the same level as Ra; and Ra, Rd, plasma lactate concentration, and the percent of glucose derived from lactate remained elevated for the duration of the experiment. These results indicate an important role of lactate in burn shock metabolism and substrate kinetics.", "contents": "Glucose and lactate kinetics in burn shock. We studied the glucose and lactate kinetics during burn shock by means of the primed constant infusion of [6-3H]glucose and Na-L-(+)-[U-14C]lactate. We found an early postburn hyperglycemia that was due to an increased rate of appearance (Ra) of glucose. Later, the ability of the tissues to extract glucose became impaired, and the plasma glucose concentration increased even more in spite of the return of Ra of glucose to the control level. The Ra of lactate rose rapidly postburn, whereas the rate of disappearance (Rd) of lactate stayed at the control level for 30 min. Consequently, plasma lactate rose approximately 350%. After 30 min, Rd of lactate increased to the same level as Ra; and Ra, Rd, plasma lactate concentration, and the percent of glucose derived from lactate remained elevated for the duration of the experiment. These results indicate an important role of lactate in burn shock metabolism and substrate kinetics."}
{"id": "PMID:15455", "title": "Treatment of Bacteroides endocarditis with carbenicillin.", "content": "A heroin addict developed acute bacterial endocarditis with Streptococcus viridans and Bacteroides melaninogenicus. Although blood cultures became negative during penicillin G and clindamycin therapy there was little clinical response. Prompt clinical improvement was achieved with intravenous carbenicillin in a dose of 40 g daily. In vitro testing supported the superiority of carbenicillin therapy in this patient.", "contents": "Treatment of Bacteroides endocarditis with carbenicillin. A heroin addict developed acute bacterial endocarditis with Streptococcus viridans and Bacteroides melaninogenicus. Although blood cultures became negative during penicillin G and clindamycin therapy there was little clinical response. Prompt clinical improvement was achieved with intravenous carbenicillin in a dose of 40 g daily. In vitro testing supported the superiority of carbenicillin therapy in this patient."}
{"id": "PMID:15460", "title": "pH gradients in the developing teeth of young mice from autoradiography of [14C]DMO.", "content": "The distribution of the weak acid [14C]DMO was studied in mice, 10-19 days old, by an autoradiographic technique that does not translocate or remove the compound. Calculations of pH values in areas of the developing teeth of these animals were made by comparing the photometric density of the distribution of [14C]DMO, as an indicator of pH, with that of 14C]NAAP, as an indicator of water content, which was reported in the companion paper. The cellular layers, i.e., odontoblasts, ameloblasts, etc., had pH values of 7.1 +/- 0.1; the pH values in enamel, predentine, and dentine ranged from 7.3 to 8.5. It is suggested that an alkaline matrix promotes nucleation and growth of hydroxyapatite.", "contents": "pH gradients in the developing teeth of young mice from autoradiography of [14C]DMO. The distribution of the weak acid [14C]DMO was studied in mice, 10-19 days old, by an autoradiographic technique that does not translocate or remove the compound. Calculations of pH values in areas of the developing teeth of these animals were made by comparing the photometric density of the distribution of [14C]DMO, as an indicator of pH, with that of 14C]NAAP, as an indicator of water content, which was reported in the companion paper. The cellular layers, i.e., odontoblasts, ameloblasts, etc., had pH values of 7.1 +/- 0.1; the pH values in enamel, predentine, and dentine ranged from 7.3 to 8.5. It is suggested that an alkaline matrix promotes nucleation and growth of hydroxyapatite."}
{"id": "PMID:15461", "title": "Computer simulation of ischemic rat heart purine metabolism. II. Model behavior.", "content": "The behavior of a model for the partial depletion of adenine nucleotides in the perfused rat heart has been compared for ischemic and high coronary flow anoxic conditions. The accumulation of noradrenaline in the interstitial fluid greatly activates adenylate cyclase ultimately resulting in the degradation of 11.02 micronmol/g dry wt of ATP to adenosine, inosine, and hypoxanthine in 30 min. The high coronary flow rate during anoxic perfusion promotes washout of the noradrenaline from the interstitial fluid so that the hormone accumulates to only one fifth of its highest level in ischemia. This results in only slight activation of adenylate cyclase and in insignificant degradation of ATP in 2 min. The behavior of the model has been examined for two aerobic conditions--a transition from light to heavy work (2 min) and a transition from substrate-free to glucose perfusion (12 min), In both cases adenylate cyclase was not activated above its basal activity, and insignificant depletion of adenine nucleotides is predicted by the model.", "contents": "Computer simulation of ischemic rat heart purine metabolism. II. Model behavior. The behavior of a model for the partial depletion of adenine nucleotides in the perfused rat heart has been compared for ischemic and high coronary flow anoxic conditions. The accumulation of noradrenaline in the interstitial fluid greatly activates adenylate cyclase ultimately resulting in the degradation of 11.02 micronmol/g dry wt of ATP to adenosine, inosine, and hypoxanthine in 30 min. The high coronary flow rate during anoxic perfusion promotes washout of the noradrenaline from the interstitial fluid so that the hormone accumulates to only one fifth of its highest level in ischemia. This results in only slight activation of adenylate cyclase and in insignificant degradation of ATP in 2 min. The behavior of the model has been examined for two aerobic conditions--a transition from light to heavy work (2 min) and a transition from substrate-free to glucose perfusion (12 min), In both cases adenylate cyclase was not activated above its basal activity, and insignificant depletion of adenine nucleotides is predicted by the model."}
{"id": "PMID:15462", "title": "Psychoneuroendocrinology of affective disorder: an overview.", "content": "Neuroendocrine function has been reported by several workers to be abnormal in affective disorder. It has been shown that neurotransmitters (noradrenaline, dopamine, and serotinin) are involved in the regulation of neuroendocrine function. Several biological hypotheses of affective disorder have implicated a defect in neurotransmitter function, but these hypotheses have been found lacking in part over the years. The study of neuroendocrine abnormalities found in various types of affective disorder may clarify some aspects of this complex issue by reflecting neurotransmitter activity in this disorder. Such studies should help further explain affective illness.", "contents": "Psychoneuroendocrinology of affective disorder: an overview. Neuroendocrine function has been reported by several workers to be abnormal in affective disorder. It has been shown that neurotransmitters (noradrenaline, dopamine, and serotinin) are involved in the regulation of neuroendocrine function. Several biological hypotheses of affective disorder have implicated a defect in neurotransmitter function, but these hypotheses have been found lacking in part over the years. The study of neuroendocrine abnormalities found in various types of affective disorder may clarify some aspects of this complex issue by reflecting neurotransmitter activity in this disorder. Such studies should help further explain affective illness."}
{"id": "PMID:15463", "title": "Spinal cord injury: a role for the psychiatrist.", "content": "The initial psychiatric evaluation of individuals with spinal cord injuries should focus on the patients' coping strategies; this information is an essential part of the treatment and rehabilitation plan. Psychiatrists can also work effectively with staff members in groups designed to ease the strain of working with severely disabled patients. Such patients may have psychiatric illnesses that are not secondary to the injury; careful selection of antidepressant or antipsychotic medication is essential. The author points out that the psychiatrist has much to offer in the treatment of individuals with spinal cord and other severely disabling injuries.", "contents": "Spinal cord injury: a role for the psychiatrist. The initial psychiatric evaluation of individuals with spinal cord injuries should focus on the patients' coping strategies; this information is an essential part of the treatment and rehabilitation plan. Psychiatrists can also work effectively with staff members in groups designed to ease the strain of working with severely disabled patients. Such patients may have psychiatric illnesses that are not secondary to the injury; careful selection of antidepressant or antipsychotic medication is essential. The author points out that the psychiatrist has much to offer in the treatment of individuals with spinal cord and other severely disabling injuries."}
{"id": "PMID:15464", "title": "Characteristics of release of duodenal gastrin.", "content": "Duodenal gastrin release in the dog was studied after mucosal antrectomy with intact duodenal innervation, following which basal gastrin levels fell. Acetylcholine at pH 7 but not at pH 1.5 and insulin hypoglycemia but not 2-deoxyglucose release duodenal gastrin. Glycine (pH7), physiologic saline (pH 7), and balloon distention failed to release duodenal gastrin. These findings suggest differences in release characteristics between canine antral and duodenal gastrin, and point out species differences between man and dog in respect to release of duodenal gastrin.", "contents": "Characteristics of release of duodenal gastrin. Duodenal gastrin release in the dog was studied after mucosal antrectomy with intact duodenal innervation, following which basal gastrin levels fell. Acetylcholine at pH 7 but not at pH 1.5 and insulin hypoglycemia but not 2-deoxyglucose release duodenal gastrin. Glycine (pH7), physiologic saline (pH 7), and balloon distention failed to release duodenal gastrin. These findings suggest differences in release characteristics between canine antral and duodenal gastrin, and point out species differences between man and dog in respect to release of duodenal gastrin."}
{"id": "PMID:15465", "title": "Intestinal brush border enzymes after short-term mesenteric ischemia.", "content": "The total activities of sucrase, trehalase, amino-peptidase, and gamma-glutamyltransferase in the isolated brush border of the entire small bowel are reduced to 35, 55, 33, and 21 per cent, respectively, of control values (p less than 0.001) 2 hours after a 45 minute occlusion of the superior mesenteric artery. Since brush border proteins are also reduced by ischemia to 42 per cent of control, enzymatic activity when expressed as U/mg protein is significantly reduced only in the case of gamma-glutamyltransferase, to 48 per cent of control.", "contents": "Intestinal brush border enzymes after short-term mesenteric ischemia. The total activities of sucrase, trehalase, amino-peptidase, and gamma-glutamyltransferase in the isolated brush border of the entire small bowel are reduced to 35, 55, 33, and 21 per cent, respectively, of control values (p less than 0.001) 2 hours after a 45 minute occlusion of the superior mesenteric artery. Since brush border proteins are also reduced by ischemia to 42 per cent of control, enzymatic activity when expressed as U/mg protein is significantly reduced only in the case of gamma-glutamyltransferase, to 48 per cent of control."}
{"id": "PMID:15467", "title": "Rapid intubation with fazadinium. A comparison of fazadinium with suxamethonium and alcuronium.", "content": "The speed of onset and intubation conditions have been compared for suxamethonium 1 mg/kg, alcuronium 0-32 mg/kg and fazadinium 1 mg/kg and 1-25 mg/kg. Fazadinium 1 mg/kg was not significantly different in times to intubation from suxamethonium although the latter gave a highly significant greater number of patients with excellent conditions. The higher dose of 1-25 mg/kg fazadinium did not give significantly better intubating conditions than the lower dose. Although the times to intubation for the two dose levels of fazadinium did not differ statistically, the higher dose was significantly slower in onset than suxamethonium. Alcuronium was slower than either suxamethonium or fazadinium 1 mg/kg in producing satisfactory conditions. The nondepolarizing drug, fazadinium, may be a useful neuromuscular blocking agent in emergency cases where rapid intubation is required and when it is wished to avoid possible or probable adverse effects from the depolarising drug suxamethonium.", "contents": "Rapid intubation with fazadinium. A comparison of fazadinium with suxamethonium and alcuronium. The speed of onset and intubation conditions have been compared for suxamethonium 1 mg/kg, alcuronium 0-32 mg/kg and fazadinium 1 mg/kg and 1-25 mg/kg. Fazadinium 1 mg/kg was not significantly different in times to intubation from suxamethonium although the latter gave a highly significant greater number of patients with excellent conditions. The higher dose of 1-25 mg/kg fazadinium did not give significantly better intubating conditions than the lower dose. Although the times to intubation for the two dose levels of fazadinium did not differ statistically, the higher dose was significantly slower in onset than suxamethonium. Alcuronium was slower than either suxamethonium or fazadinium 1 mg/kg in producing satisfactory conditions. The nondepolarizing drug, fazadinium, may be a useful neuromuscular blocking agent in emergency cases where rapid intubation is required and when it is wished to avoid possible or probable adverse effects from the depolarising drug suxamethonium."}
{"id": "PMID:15473", "title": "Depression of phase-transition temperature in a model cell membrane by local anesthetics.", "content": "Disordering, fluidizing and dilating effects of anesthetics upon cell membranes are well recognized. The fluidization can be precisely measured with phospholipid membranes. When phospholipids are dispersed in water, they form globules of bilayer structure. These model membranes undergo transition between crystalline (ordered and less fluid) and liquid crystalline (less ordered and fluid) phases according to the temperature, the degree of packing of each molecule, and the chemical environment. The phase transition occurs in a cooperative fashion and the turbidity of the dispersion changes abruptly, clear in liquid crystalline phase and turbid in crystalline phase. The present study was undertaken to quantitate the fluidizing effects of local anesthetics on dipalmitoyl lecithin (DPL) bilayer dispersion by measuring the turbidity change. Tetracaine, bupivacaine, lidocaine, and procaine were studied. They all depressed the phase-transition temperature. The binding of the drugs to the model membrane followed unsaturable kinetics, and the pH titration curve showed that only uncharged molecules were active. The freezing point depression was analyzed according to the Van't Hoff model. From this model, the partition coefficients of the uncharged molecules between DPL and water were estimated: lidocaine 76, procaine 159, bupivacaine 812, and tetracaine 1,405. The concentration of local anesthetics in the DPL phase needed to decrease the phase-transition temperature 1 degree C showed a constant value of 0.132 M. The concentration of local anesthetics in the DPL phase is a function of pH, partition coefficient, and volume ratio between the DPL and aqueous phases. The normalized values of the fluidizing action of these drugs at physiologic conditions correlated well with their nerve-blocking potencies. The present results indicate that the uncharged molecules fluidize the lecithin membrane by unsaturable nonspecific binding. The possible effect of the charged molecules upon the fluidity of natural membranes remains to be established.", "contents": "Depression of phase-transition temperature in a model cell membrane by local anesthetics. Disordering, fluidizing and dilating effects of anesthetics upon cell membranes are well recognized. The fluidization can be precisely measured with phospholipid membranes. When phospholipids are dispersed in water, they form globules of bilayer structure. These model membranes undergo transition between crystalline (ordered and less fluid) and liquid crystalline (less ordered and fluid) phases according to the temperature, the degree of packing of each molecule, and the chemical environment. The phase transition occurs in a cooperative fashion and the turbidity of the dispersion changes abruptly, clear in liquid crystalline phase and turbid in crystalline phase. The present study was undertaken to quantitate the fluidizing effects of local anesthetics on dipalmitoyl lecithin (DPL) bilayer dispersion by measuring the turbidity change. Tetracaine, bupivacaine, lidocaine, and procaine were studied. They all depressed the phase-transition temperature. The binding of the drugs to the model membrane followed unsaturable kinetics, and the pH titration curve showed that only uncharged molecules were active. The freezing point depression was analyzed according to the Van't Hoff model. From this model, the partition coefficients of the uncharged molecules between DPL and water were estimated: lidocaine 76, procaine 159, bupivacaine 812, and tetracaine 1,405. The concentration of local anesthetics in the DPL phase needed to decrease the phase-transition temperature 1 degree C showed a constant value of 0.132 M. The concentration of local anesthetics in the DPL phase is a function of pH, partition coefficient, and volume ratio between the DPL and aqueous phases. The normalized values of the fluidizing action of these drugs at physiologic conditions correlated well with their nerve-blocking potencies. The present results indicate that the uncharged molecules fluidize the lecithin membrane by unsaturable nonspecific binding. The possible effect of the charged molecules upon the fluidity of natural membranes remains to be established."}
{"id": "PMID:15474", "title": "Mutagenicity of halogenated ether anesthetics.", "content": "An in vitro microbial assay system employing two histidine-dependent strains of Salmonella typhimurium, TA1535 and TA100, was used to test the mutagenicities of enflurane, methoxyflurane, isoflurane and fluroxene. Enflurane, isoflurane and fluroxene in concentrations ranging from 0.01 to 30 per cent and methoxyflurane in concentrations ranging from 0.01 to 7 per cent were incubated with bacteria in the presence or absence of homogenates of liver prepared from rats pretreated with the enzyme inducer, Aroclor 1254. Enflurane, methoxyflurane, isoflurane, and urines from patients anesthetized with these agents were not mutagenic. Fluroxene, however, was highly mutagenic, and therefore poses a possible hazard for operating room personnel and patients.", "contents": "Mutagenicity of halogenated ether anesthetics. An in vitro microbial assay system employing two histidine-dependent strains of Salmonella typhimurium, TA1535 and TA100, was used to test the mutagenicities of enflurane, methoxyflurane, isoflurane and fluroxene. Enflurane, isoflurane and fluroxene in concentrations ranging from 0.01 to 30 per cent and methoxyflurane in concentrations ranging from 0.01 to 7 per cent were incubated with bacteria in the presence or absence of homogenates of liver prepared from rats pretreated with the enzyme inducer, Aroclor 1254. Enflurane, methoxyflurane, isoflurane, and urines from patients anesthetized with these agents were not mutagenic. Fluroxene, however, was highly mutagenic, and therefore poses a possible hazard for operating room personnel and patients."}
{"id": "PMID:15471", "title": "Mechanisms of chronotropic effects of volatile inhalation anesthetics.", "content": "The chronotropic effects of all currently available volatile anesthetics were investigated in isolated rat atrial preparations. Anesthetic ethers, diethyl ether, methoxyflurane, and enflurane elicited a dose-dependent positive chronotropic effect. Fluroxene produced a slight depression at low concentrations. The halogenated hydrocarbon anesthetics, halothane, chloroform, and trichloroethylene, did not show a uniform pattern. Halothane's effect was small and biphasic. Chloroform caused a dose-dependent decrease in heart rate, and trichloroethylene caused a marked positive chronotropic effect. The dose-response curves in all anesthetics remained unaltered in the presence of either 3 x 10(-7) M dl-propranolol or 1 x 10(-6) M atropine. It is concluded that volatile anesthetics elicit significant direct chronotropic actions on rat atrial preparations. The mechanism of their actions does not involve stimulation of beta-adrenergic or cholinergic receptors.", "contents": "Mechanisms of chronotropic effects of volatile inhalation anesthetics. The chronotropic effects of all currently available volatile anesthetics were investigated in isolated rat atrial preparations. Anesthetic ethers, diethyl ether, methoxyflurane, and enflurane elicited a dose-dependent positive chronotropic effect. Fluroxene produced a slight depression at low concentrations. The halogenated hydrocarbon anesthetics, halothane, chloroform, and trichloroethylene, did not show a uniform pattern. Halothane's effect was small and biphasic. Chloroform caused a dose-dependent decrease in heart rate, and trichloroethylene caused a marked positive chronotropic effect. The dose-response curves in all anesthetics remained unaltered in the presence of either 3 x 10(-7) M dl-propranolol or 1 x 10(-6) M atropine. It is concluded that volatile anesthetics elicit significant direct chronotropic actions on rat atrial preparations. The mechanism of their actions does not involve stimulation of beta-adrenergic or cholinergic receptors."}
{"id": "PMID:15475", "title": "[Study of a new anesthetic agent: Etomidate (R 26490). Unusual electroencephalic aspects].", "content": "Etomidate or R 26490 is a new hypnotic agent produced by JANSSEN and al. in 1971. The first human experimentation was performed in 1972. The authors used Etomidate for 300 anaesthetics given for neuroradiological investigations. Two protocols were used for study: 25 anaesthetics were given with Etomidate as sole anaesthetic to outline its specific properties; 275 angiographies were performed with a combination of Etomidate and fentany1. In protocol no 1, the mean consumption was for 1,85 mg/kg/h, in protocol no2, the mean consumption was of 0,9 mg/kg/h. Pharmacological study of this drug defines it as a short acting hypnotic agent of low toxicity. Clinical observation shows cardiovascular and respiratory stability. However, frequent myoclonias were noted, when Etomidate was given as a sole anaesthetic. EEG recording and evoked response encephalography helped to outline some effects of Etomidate on central nervous system.", "contents": "[Study of a new anesthetic agent: Etomidate (R 26490). Unusual electroencephalic aspects]. Etomidate or R 26490 is a new hypnotic agent produced by JANSSEN and al. in 1971. The first human experimentation was performed in 1972. The authors used Etomidate for 300 anaesthetics given for neuroradiological investigations. Two protocols were used for study: 25 anaesthetics were given with Etomidate as sole anaesthetic to outline its specific properties; 275 angiographies were performed with a combination of Etomidate and fentany1. In protocol no 1, the mean consumption was for 1,85 mg/kg/h, in protocol no2, the mean consumption was of 0,9 mg/kg/h. Pharmacological study of this drug defines it as a short acting hypnotic agent of low toxicity. Clinical observation shows cardiovascular and respiratory stability. However, frequent myoclonias were noted, when Etomidate was given as a sole anaesthetic. EEG recording and evoked response encephalography helped to outline some effects of Etomidate on central nervous system."}
{"id": "PMID:15472", "title": "Arrhythmic doses of epinephrine and dopamine during halothane, enflurane, methoxyflurane, and fluroxene anesthesia in goats.", "content": "The cardiac arrhythmicity of epinephrine and dopamine was compared in awake goats and during approximate equivalent levels of halothane, enflurane, methoxyflurane, and fluroxene anesthesia. The arrhythmic threshold dose for epinephrine and dopamine was significantly (p less than 0.05) reduced during halothane anesthesia when compared to values determined in awake animals. Enflurane anesthesia had no significant affect on the arrhythmic threshold dose for either catecholamine. However, methoxyflurane and fluroxene anesthesia significantly (p less than 0.05) elevated the arrhythmic threshold dose for dopamine. Epinephrine produced greater elevations in mean arterial pressure than dopamine with all anesthetics except enflurane, and dopamine produced significantly (p less than 0.05) higher heart rates in the awake animals and those anesthetized with halothane and enflurane. The authors conclude that, in terms of arrhythmic potential, there is no advantage in the use of dopamine rather than epinephrine for the reversal of halothane-induced myocardial depression during halothane or enflurane anesthesia.", "contents": "Arrhythmic doses of epinephrine and dopamine during halothane, enflurane, methoxyflurane, and fluroxene anesthesia in goats. The cardiac arrhythmicity of epinephrine and dopamine was compared in awake goats and during approximate equivalent levels of halothane, enflurane, methoxyflurane, and fluroxene anesthesia. The arrhythmic threshold dose for epinephrine and dopamine was significantly (p less than 0.05) reduced during halothane anesthesia when compared to values determined in awake animals. Enflurane anesthesia had no significant affect on the arrhythmic threshold dose for either catecholamine. However, methoxyflurane and fluroxene anesthesia significantly (p less than 0.05) elevated the arrhythmic threshold dose for dopamine. Epinephrine produced greater elevations in mean arterial pressure than dopamine with all anesthetics except enflurane, and dopamine produced significantly (p less than 0.05) higher heart rates in the awake animals and those anesthetized with halothane and enflurane. The authors conclude that, in terms of arrhythmic potential, there is no advantage in the use of dopamine rather than epinephrine for the reversal of halothane-induced myocardial depression during halothane or enflurane anesthesia."}
{"id": "PMID:15476", "title": "[Effects of Etomidate on ventilation and blood gases].", "content": "17 surgical patients, agent 49 to 87, are studied. Their anaesthetic induction was performed by an intravenous injection of Etomidate on a 0,23 mg/kg body weight basiis. Respiratory frequency and minute ventilation were put on continuous recording, PO2, PCO2 and arterial blood pH were measured 1,3 and 5 minutes after injection of the drug. Anaesthetic induction, occuring 10 seconds after injection of the drug, was followed by an increase in respiratory frequency (32 p 100) and a rather modest increase of minute ventilation (9,2 p. 100). Among blood gases measurements, only PaO2 showed a decrease of 6,7 p. 100, when PO2 and pH remained practically unchanged. The small increase in minute ventilation, compared with a relatively important increase in respiratory frequency, suggests some decrease in efficient alveolar ventilation without however affecting blood gases in an important fashion.", "contents": "[Effects of Etomidate on ventilation and blood gases]. 17 surgical patients, agent 49 to 87, are studied. Their anaesthetic induction was performed by an intravenous injection of Etomidate on a 0,23 mg/kg body weight basiis. Respiratory frequency and minute ventilation were put on continuous recording, PO2, PCO2 and arterial blood pH were measured 1,3 and 5 minutes after injection of the drug. Anaesthetic induction, occuring 10 seconds after injection of the drug, was followed by an increase in respiratory frequency (32 p 100) and a rather modest increase of minute ventilation (9,2 p. 100). Among blood gases measurements, only PaO2 showed a decrease of 6,7 p. 100, when PO2 and pH remained practically unchanged. The small increase in minute ventilation, compared with a relatively important increase in respiratory frequency, suggests some decrease in efficient alveolar ventilation without however affecting blood gases in an important fashion."}
{"id": "PMID:15477", "title": "[Hemodynamic effects of Etomidate].", "content": "Hemodynamic variations due to Etomidate administration were studies in 10 patients submitted to artificial ventilation. Etomidate was given at a 0.37 mg/kg B.W. dosage. Cardiac rate, mean arterial B.P., C.V.P., mean arteial pulmonary pressure, mean pulmonary capillary pressure and cardiac output were investigated. From values found, systolic output, systemic vascular resistance, and pulmonary arteriolar resistance were calculated. Results show that Etomidate has little effect on hemodynamics. There is only a 5 p. 100 increase in cardiac rate, a 16p. 100 decrease in cardiac output, 1 18 p. 100 decrease in systolic output and a 12p. 100 decrease in mean arterial B.P. Variations of mean capillary pressure, of systemic vascular resistance and of pulmonary arteriolar resistance are not significant.", "contents": "[Hemodynamic effects of Etomidate]. Hemodynamic variations due to Etomidate administration were studies in 10 patients submitted to artificial ventilation. Etomidate was given at a 0.37 mg/kg B.W. dosage. Cardiac rate, mean arterial B.P., C.V.P., mean arteial pulmonary pressure, mean pulmonary capillary pressure and cardiac output were investigated. From values found, systolic output, systemic vascular resistance, and pulmonary arteriolar resistance were calculated. Results show that Etomidate has little effect on hemodynamics. There is only a 5 p. 100 increase in cardiac rate, a 16p. 100 decrease in cardiac output, 1 18 p. 100 decrease in systolic output and a 12p. 100 decrease in mean arterial B.P. Variations of mean capillary pressure, of systemic vascular resistance and of pulmonary arteriolar resistance are not significant."}
{"id": "PMID:15478", "title": "[Use of the diazepam-pentazocine (pentazepam) combination in anesthesiology].", "content": "The authors report on 50 surgical or endoscopic cases in which local or regional anaesthesia was completed with  a combination of diazepam and pentazocine (Pentazapam). This \"diazanalgesia\" was performed either as a routine or as a complement to regional anaesthesia (mostly an epidural) in which restlessness or insufficient analgesia were noted. Both drugs are injected separately. Diazepam being used to combat anxiety and pentazocine to allay pain. Sedation was considered to be sufficient in 43 cases out of 50 and analgesia in 47 cases out of 50. In all but one case, recovery was calm. In 24 cases, the patients regained consciensness quickly. There was only little effect on respiratory frequency, blood gases, blood pressure or cardiac rate. Thus, pentazepam combination can be considered as a useful method of \"wake diazanalgesia\" as far as it is used to complement a local or regional anaesthesia. This technique seems particularly useful in the aged or bad risk patient because of its moderate cardiovascular or respiratory aciton.", "contents": "[Use of the diazepam-pentazocine (pentazepam) combination in anesthesiology]. The authors report on 50 surgical or endoscopic cases in which local or regional anaesthesia was completed with  a combination of diazepam and pentazocine (Pentazapam). This \"diazanalgesia\" was performed either as a routine or as a complement to regional anaesthesia (mostly an epidural) in which restlessness or insufficient analgesia were noted. Both drugs are injected separately. Diazepam being used to combat anxiety and pentazocine to allay pain. Sedation was considered to be sufficient in 43 cases out of 50 and analgesia in 47 cases out of 50. In all but one case, recovery was calm. In 24 cases, the patients regained consciensness quickly. There was only little effect on respiratory frequency, blood gases, blood pressure or cardiac rate. Thus, pentazepam combination can be considered as a useful method of \"wake diazanalgesia\" as far as it is used to complement a local or regional anaesthesia. This technique seems particularly useful in the aged or bad risk patient because of its moderate cardiovascular or respiratory aciton."}
{"id": "PMID:15479", "title": "[Toxico-pharmacologic study of a curarimimetic, AH 8165, in relation to storage time].", "content": "The toxicological and pharmacological study of a non depolarizing curariform drug AH 8165 was performed under various conditions of storage, duration and temperature (duration: 1 month 2 years; temperature: 4 degrees C to 70 degrees C). It shows that this drug ought to be kept a low temperature for storage (in the range of + 4 degrees C). In the sam way, this study demonstrates a better stability of this drug when stored lyophilized form instead of a solute. The interest of standardized animal experimentation in studying the activity of a therapeutic substance depending on the duration of storage is shown.", "contents": "[Toxico-pharmacologic study of a curarimimetic, AH 8165, in relation to storage time]. The toxicological and pharmacological study of a non depolarizing curariform drug AH 8165 was performed under various conditions of storage, duration and temperature (duration: 1 month 2 years; temperature: 4 degrees C to 70 degrees C). It shows that this drug ought to be kept a low temperature for storage (in the range of + 4 degrees C). In the sam way, this study demonstrates a better stability of this drug when stored lyophilized form instead of a solute. The interest of standardized animal experimentation in studying the activity of a therapeutic substance depending on the duration of storage is shown."}
{"id": "PMID:15480", "title": "[Effects of Alfatesine (ct 1341) on cerebral blood flow and metabolism in man. Global and regional changes].", "content": "The effects of Alfatesine on local cerebral blood flow  and on cerebral oxygen consumption were studied in 5 normal subjects and in 6 patients suffering from diffuse vascular repercussion of cerebral distress. There is a 75 p. 100 fall in cerebral  blood flow in the gray substance and a parallel fall in oxygen consumption. At rest, the caracteristic anaesthetic action modifies the caracteristical distribution of blood flows in the cortex. A relative hyperemia appears in the area of the central sulcus. Those focal changes could not be found in the group of pathogical patients.", "contents": "[Effects of Alfatesine (ct 1341) on cerebral blood flow and metabolism in man. Global and regional changes]. The effects of Alfatesine on local cerebral blood flow  and on cerebral oxygen consumption were studied in 5 normal subjects and in 6 patients suffering from diffuse vascular repercussion of cerebral distress. There is a 75 p. 100 fall in cerebral  blood flow in the gray substance and a parallel fall in oxygen consumption. At rest, the caracteristic anaesthetic action modifies the caracteristical distribution of blood flows in the cortex. A relative hyperemia appears in the area of the central sulcus. Those focal changes could not be found in the group of pathogical patients."}
{"id": "PMID:15481", "title": "[Correction of the alphamimetic effects of metaraminol by nicergoline].", "content": "In this work, the authors are studying the cardio-vascular effects of nicergoline. To do so, the drug is made to compete with metaraminol whose dominant alphamimetic effects are known. This experimentation was performed in 7 patients in coma stage III or IV and whose vascular receptors were active. Those 7 patients were submitted continuous metaraminol perfusion and a steady state vasoconstriction was thus obtained. A single intravenous injection of 10 mg nicergoline resulted in vasodilation with a fall in vascular resistance and a moderate fall in mean blood pressure. Cardiac output remained unchanged. This work confirme thus the alphasympatholytic effects of nicergoline.", "contents": "[Correction of the alphamimetic effects of metaraminol by nicergoline]. In this work, the authors are studying the cardio-vascular effects of nicergoline. To do so, the drug is made to compete with metaraminol whose dominant alphamimetic effects are known. This experimentation was performed in 7 patients in coma stage III or IV and whose vascular receptors were active. Those 7 patients were submitted continuous metaraminol perfusion and a steady state vasoconstriction was thus obtained. A single intravenous injection of 10 mg nicergoline resulted in vasodilation with a fall in vascular resistance and a moderate fall in mean blood pressure. Cardiac output remained unchanged. This work confirme thus the alphasympatholytic effects of nicergoline."}
{"id": "PMID:15482", "title": "[Continuous measurement of arterial pressure by means of an arterial catheter. Its value in secondary transport].", "content": "It is of no much use to try to assess the cardiovascular condition of patients with impending or confirmed shock by taking the blood pressure with the classical arm cuff, especially if arterfacts such as noise, vibrations, shaking etc... are interfering. Instant continuous measurement of blood pressure by means of arterial cannulation avoids those drawbacks and is a sure and efficient method of assessment of an often unstable, precarious and sometimes aggravated cardio-vascular condition by the very transportation. The S.A.M.U. of Montpellier used this technique in 15 cases. The authors are reporting their experience and also are evoking some technical problems that may occur.", "contents": "[Continuous measurement of arterial pressure by means of an arterial catheter. Its value in secondary transport]. It is of no much use to try to assess the cardiovascular condition of patients with impending or confirmed shock by taking the blood pressure with the classical arm cuff, especially if arterfacts such as noise, vibrations, shaking etc... are interfering. Instant continuous measurement of blood pressure by means of arterial cannulation avoids those drawbacks and is a sure and efficient method of assessment of an often unstable, precarious and sometimes aggravated cardio-vascular condition by the very transportation. The S.A.M.U. of Montpellier used this technique in 15 cases. The authors are reporting their experience and also are evoking some technical problems that may occur."}
{"id": "PMID:15484", "title": "[Use of constant perithoracic negative pressure in the transport of newborn infants with severe forms of idiopathic respiratory distress].", "content": "The authors used for transportation of neonates in severe idiopathic respiratory distress the continuous perithoracic negative pressure method suggested by OUTBRIGE and STERN in neonate intensive care. The authors are describing the material used and are presenting their first encouraging results. This technique improves conditions and therapeutic efficiency in thus treated infants. The easy handling and accessibility of apparatus constitue an efficient and not too aggressive mean of treatment of those particularly frail and difficult to treat infants during transportation.", "contents": "[Use of constant perithoracic negative pressure in the transport of newborn infants with severe forms of idiopathic respiratory distress]. The authors used for transportation of neonates in severe idiopathic respiratory distress the continuous perithoracic negative pressure method suggested by OUTBRIGE and STERN in neonate intensive care. The authors are describing the material used and are presenting their first encouraging results. This technique improves conditions and therapeutic efficiency in thus treated infants. The easy handling and accessibility of apparatus constitue an efficient and not too aggressive mean of treatment of those particularly frail and difficult to treat infants during transportation."}
{"id": "PMID:15485", "title": "[Do enzyme determinations have any prognostic value in neurotraumatology?].", "content": "In 34 cases of skull traumas and in 14 cases of acute cerebral accidents, CK, GOT, GPT, LDH and its isoenzymes were assessed in the patient's serum and CSF. Results show that the increase of the enzymatic level in the CSF seems due to cerebral tissue damage for the main part, when in the serum the increase is influenced by combined traumas. The CSF dosages allow to define a threshold of severeness, unlike serum dosages without any pronostic value.", "contents": "[Do enzyme determinations have any prognostic value in neurotraumatology?]. In 34 cases of skull traumas and in 14 cases of acute cerebral accidents, CK, GOT, GPT, LDH and its isoenzymes were assessed in the patient's serum and CSF. Results show that the increase of the enzymatic level in the CSF seems due to cerebral tissue damage for the main part, when in the serum the increase is influenced by combined traumas. The CSF dosages allow to define a threshold of severeness, unlike serum dosages without any pronostic value."}
{"id": "PMID:15486", "title": "[Value of cerebral metabolic exploration in post-traumatic coma states in the acute phase].", "content": "The authors report the values of mean hemispheric blood-flow and cerebral arterial consumption they found in 34 neurosurgical comatous cases in acute state. In basal conditions, mean values of mean hemispheric bloodflow and oxygen consumption are lowered. There seems to be a relation between the values found and the comatous stage on one hand, the prognosis on the other hand. The cerebral response to hypercapnia (16 assays) allows to separate 2 groups, one with a noticeable improvement of cerebral bloodflow, the other with only a minimal response. There was no significant variation of cerebral oxygen consumption in both group. Cerebral response to CO2 seems to be clearly related to the stage of coma (low in the most severe cases) but pronostic incidence remained uncertain. A hypertensive test by means of Aramine (18 assays) allows to separate 3 groups : 1 group (8 cases) where the mean hemispheric bloodflow remained stable during hypertension as did the cerebral oxygen consumption -(autoregulation remained unchanged), 1 group (4 cases) where mean hemispheric bloodflow and cerebral oxygen consumption were lowered (excessive autoregulation), 1 group (6 cases) where mean hemispheric bloodflow increases clearly while under Aramine perfusion (loss of autoregulation). Those dynamic tests, either hypercapnic or hypertensive, allow, in comparing oxygen consumption variations with cerebral bloodflow variations, the distinction between : patients where metabolic autoregulation seems maintained (good prognosis) - (10 cases), patients where metabolic regulation is lost with either \"luxury perfusion\" (14 cases) - poor prognosis, or \"insufficient perfusion\" (10 cases). The authors are discussing the treatment concerning those last mentioned patients.", "contents": "[Value of cerebral metabolic exploration in post-traumatic coma states in the acute phase]. The authors report the values of mean hemispheric blood-flow and cerebral arterial consumption they found in 34 neurosurgical comatous cases in acute state. In basal conditions, mean values of mean hemispheric bloodflow and oxygen consumption are lowered. There seems to be a relation between the values found and the comatous stage on one hand, the prognosis on the other hand. The cerebral response to hypercapnia (16 assays) allows to separate 2 groups, one with a noticeable improvement of cerebral bloodflow, the other with only a minimal response. There was no significant variation of cerebral oxygen consumption in both group. Cerebral response to CO2 seems to be clearly related to the stage of coma (low in the most severe cases) but pronostic incidence remained uncertain. A hypertensive test by means of Aramine (18 assays) allows to separate 3 groups : 1 group (8 cases) where the mean hemispheric bloodflow remained stable during hypertension as did the cerebral oxygen consumption -(autoregulation remained unchanged), 1 group (4 cases) where mean hemispheric bloodflow and cerebral oxygen consumption were lowered (excessive autoregulation), 1 group (6 cases) where mean hemispheric bloodflow increases clearly while under Aramine perfusion (loss of autoregulation). Those dynamic tests, either hypercapnic or hypertensive, allow, in comparing oxygen consumption variations with cerebral bloodflow variations, the distinction between : patients where metabolic autoregulation seems maintained (good prognosis) - (10 cases), patients where metabolic regulation is lost with either \"luxury perfusion\" (14 cases) - poor prognosis, or \"insufficient perfusion\" (10 cases). The authors are discussing the treatment concerning those last mentioned patients."}
{"id": "PMID:15487", "title": "Characteristics of two new reticuloendotheliosis virus isolates of turkeys.", "content": "Reticuloendotheliosis (RE) virus strains MN81 and MN67 isolated from epiornithics of RE in turkeys were partially characterized. Strains MN81 and MN67 replicated in chicken embryo fibroblast,duck embryo fibroblast and turkey embryo-fibroblast cultures and produced syncytial cytopathic effects in duck embryo fibroblast and turkey embryo fibroblast cultures. The virions of MN81 and MN67 measured approximately 100 nm in diameter, resembled RE virus strain T, and could be distinguished from avian leukosis viruses morphologically. The buoyant density of strain MN81 was found to be 1.15 g/cm3 in sucrose gradients. Strains MN81 and MN67 were inactivated by heat, acid pH, ether, and chloroform treatments. These strains were serologically unrelated to avian leukosis virus but were related to RE virus strains T, CS, DIA, and SN.", "contents": "Characteristics of two new reticuloendotheliosis virus isolates of turkeys. Reticuloendotheliosis (RE) virus strains MN81 and MN67 isolated from epiornithics of RE in turkeys were partially characterized. Strains MN81 and MN67 replicated in chicken embryo fibroblast,duck embryo fibroblast and turkey embryo-fibroblast cultures and produced syncytial cytopathic effects in duck embryo fibroblast and turkey embryo fibroblast cultures. The virions of MN81 and MN67 measured approximately 100 nm in diameter, resembled RE virus strain T, and could be distinguished from avian leukosis viruses morphologically. The buoyant density of strain MN81 was found to be 1.15 g/cm3 in sucrose gradients. Strains MN81 and MN67 were inactivated by heat, acid pH, ether, and chloroform treatments. These strains were serologically unrelated to avian leukosis virus but were related to RE virus strains T, CS, DIA, and SN."}
{"id": "PMID:15488", "title": "Body position and mode of ventilation influences arterial pH, oxygen, and carbon dioxide tensions in halothane-anesthetized horses.", "content": "Effects of body position and type of ventilation were determined on arterial blood gases (PaO2, PaCO2) and pH during and immediately following clinical halothane anesthesia in 36 young, physically conditioned horses. Horses in dorsal recumbency had a lower PaO2 than did similarly breathing horses in a lateral position. Predictably controlled positive-pressure ventilation inproved arterial oxygenation and permitted maintenance of a normal PaCO2. Most horses, regardless of type of ventilation and operative body positioning, were hypoxemic in the immediate postanesthetic period.", "contents": "Body position and mode of ventilation influences arterial pH, oxygen, and carbon dioxide tensions in halothane-anesthetized horses. Effects of body position and type of ventilation were determined on arterial blood gases (PaO2, PaCO2) and pH during and immediately following clinical halothane anesthesia in 36 young, physically conditioned horses. Horses in dorsal recumbency had a lower PaO2 than did similarly breathing horses in a lateral position. Predictably controlled positive-pressure ventilation inproved arterial oxygenation and permitted maintenance of a normal PaCO2. Most horses, regardless of type of ventilation and operative body positioning, were hypoxemic in the immediate postanesthetic period."}
{"id": "PMID:15489", "title": "Effects of electroanesthesia and a phenothiazine tranquilizer on thermoregulation in the sheep.", "content": "The effects of giving propiopromazine alone and of electroanesthesia-propiopromazine treatment on thermoregulation (body temperature regulation) were studied in 3 sheep at ambient temperatures of 5, 25, and 35 C. Measures of thermoregulation during a 120-minute treatment and 120-treatment recovery period included rectal temperature, respiratory frequency, respiratory evaporative heat loss, metabolic heat production, multiple skin temperatures, and shivering. During cold exposure (5 C), both the propiopromazine administration and the electroanesthesia-propiopromazine treatment resulted in hypothermia which was attributed to increased peripheral and respiratory heat losses, a transient inhibition of shivering thermogenesis, and a reduction in metabolic heat production. At 35 C ambient temperature, both resulted in hyperthermia caused principally by a reduction in respiratory evaporative heat loss. The effects of electroanesthesia-propiopromazine treatment on thermoregulation appeared to be additive at both the cold (5 C) and the hot (35 C) environments, in that simultaneous administration resulted in a more profound thermoregulatory impairment. Nevertheless, shifts in body temperature during electroanesthesia are partly attributable to phenothiazine premedication.", "contents": "Effects of electroanesthesia and a phenothiazine tranquilizer on thermoregulation in the sheep. The effects of giving propiopromazine alone and of electroanesthesia-propiopromazine treatment on thermoregulation (body temperature regulation) were studied in 3 sheep at ambient temperatures of 5, 25, and 35 C. Measures of thermoregulation during a 120-minute treatment and 120-treatment recovery period included rectal temperature, respiratory frequency, respiratory evaporative heat loss, metabolic heat production, multiple skin temperatures, and shivering. During cold exposure (5 C), both the propiopromazine administration and the electroanesthesia-propiopromazine treatment resulted in hypothermia which was attributed to increased peripheral and respiratory heat losses, a transient inhibition of shivering thermogenesis, and a reduction in metabolic heat production. At 35 C ambient temperature, both resulted in hyperthermia caused principally by a reduction in respiratory evaporative heat loss. The effects of electroanesthesia-propiopromazine treatment on thermoregulation appeared to be additive at both the cold (5 C) and the hot (35 C) environments, in that simultaneous administration resulted in a more profound thermoregulatory impairment. Nevertheless, shifts in body temperature during electroanesthesia are partly attributable to phenothiazine premedication."}
{"id": "PMID:15490", "title": "Microimmunodiffusion test for detection of antibodies to infectious bovine rhinotracheitis virus in bovine serum.", "content": "A microimmunodiffusion test (MIDT) specific for detection of antibodies to infectious bovine rhinotracheitis (IBR) in bovine serum has been developed. The antigen used in the MIDT was prepared from IBR virus-infected Madin-Darby bovine kidney cells grown in tissue culture. The antigen was stable, and relatively high yields were obtained readily. Results of the MIDT were obtained within 48 hours and agreed with those of the serum-neutralization test.", "contents": "Microimmunodiffusion test for detection of antibodies to infectious bovine rhinotracheitis virus in bovine serum. A microimmunodiffusion test (MIDT) specific for detection of antibodies to infectious bovine rhinotracheitis (IBR) in bovine serum has been developed. The antigen used in the MIDT was prepared from IBR virus-infected Madin-Darby bovine kidney cells grown in tissue culture. The antigen was stable, and relatively high yields were obtained readily. Results of the MIDT were obtained within 48 hours and agreed with those of the serum-neutralization test."}
{"id": "PMID:15491", "title": "The syndrome of inappropriate secretion of antidiuretic hormone associated with anaerobic thoracic empyema.", "content": "The syndrome of inappropriate secretion of antidiuretic hormone has been associated with many pulmonary diseases, including tuberculosis and bacterial and viral pneumonia: however, it has not been reported with anaerobic infections or empyema in the absence of pneumonia. We report a patient with empyema due to Bacteroides melaninogenicus, Bacteroides oralis, and Peptostreptococcus who developed the syndrome. Eight hours before the start of therapy, his serum sodium concentration was 127 mEq per liter; serum osmolality, 255 mOsm per kg; urine osmolality, 522 mOsm per kg; urinary sodium concentration, 39 mEq per liter. The creatinine clearance and the adrenocorticotropic hormone stimulation test were normal, and there was no evidence of dehydration. No other causes of the syndrome of inappropriate secretion of antidiuretic hormone were apparent. With drainage and antimicrobial drug therapy, the empyema cleared, and the syndrome resolved in 8 days. The patient has been well, without evidence of inappropriate secretion of antidiuretic hormone, for 9 months. Anaerobic infections and/or empyema without pneumonia can be associated with the syndrome of inappropriate secretion of antidiuretic hormone.", "contents": "The syndrome of inappropriate secretion of antidiuretic hormone associated with anaerobic thoracic empyema. The syndrome of inappropriate secretion of antidiuretic hormone has been associated with many pulmonary diseases, including tuberculosis and bacterial and viral pneumonia: however, it has not been reported with anaerobic infections or empyema in the absence of pneumonia. We report a patient with empyema due to Bacteroides melaninogenicus, Bacteroides oralis, and Peptostreptococcus who developed the syndrome. Eight hours before the start of therapy, his serum sodium concentration was 127 mEq per liter; serum osmolality, 255 mOsm per kg; urine osmolality, 522 mOsm per kg; urinary sodium concentration, 39 mEq per liter. The creatinine clearance and the adrenocorticotropic hormone stimulation test were normal, and there was no evidence of dehydration. No other causes of the syndrome of inappropriate secretion of antidiuretic hormone were apparent. With drainage and antimicrobial drug therapy, the empyema cleared, and the syndrome resolved in 8 days. The patient has been well, without evidence of inappropriate secretion of antidiuretic hormone, for 9 months. Anaerobic infections and/or empyema without pneumonia can be associated with the syndrome of inappropriate secretion of antidiuretic hormone."}
{"id": "PMID:15492", "title": "[Study on L-malic acid catabolism by \"Lactobacillus casei\" cells immobilized into polyacrylamide gel lattice (author's transl)].", "content": "Study on L-malic acid catabolism by Lactobacillus casei cells immobilized into polyacrylamide gel lattice has shown that the pH profil of malic acid decarboxylase activity does not differ significantly from that of free cells. The apparent enzymatic constant value as determined by the Warburg manometric method is 5 X 10(-3) M for free cells and 1.25 X 10(-2) M for immobilized cells. Malic acid decarboxylase activity can be preserved in immobilized cells over a 12 month period when the reaction vessel is fed continuously with the growth medium. It is noteworthy that the reaction vessel is similar to a constant activity reactor whose apparent enzymatic constant value, of 6,25 X 10(-3) M, does not differ significantly from that of free cells. Labelling of the cells with 14C-glycin has shown that the immobilized cells released 14 per cent of the radioactivity over a 65 hour period, indicating that the cells are possibly in a non proliferating state. After 9 months of working, a large fraction of viable bacterial cells can be isolated again. The use of such a reactor for producing metabolites is proposed.", "contents": "[Study on L-malic acid catabolism by \"Lactobacillus casei\" cells immobilized into polyacrylamide gel lattice (author's transl)]. Study on L-malic acid catabolism by Lactobacillus casei cells immobilized into polyacrylamide gel lattice has shown that the pH profil of malic acid decarboxylase activity does not differ significantly from that of free cells. The apparent enzymatic constant value as determined by the Warburg manometric method is 5 X 10(-3) M for free cells and 1.25 X 10(-2) M for immobilized cells. Malic acid decarboxylase activity can be preserved in immobilized cells over a 12 month period when the reaction vessel is fed continuously with the growth medium. It is noteworthy that the reaction vessel is similar to a constant activity reactor whose apparent enzymatic constant value, of 6,25 X 10(-3) M, does not differ significantly from that of free cells. Labelling of the cells with 14C-glycin has shown that the immobilized cells released 14 per cent of the radioactivity over a 65 hour period, indicating that the cells are possibly in a non proliferating state. After 9 months of working, a large fraction of viable bacterial cells can be isolated again. The use of such a reactor for producing metabolites is proposed."}
{"id": "PMID:15494", "title": "[Cross reactions of higher type-specific capsular polysaccharides of Klebsiella in antipneumococcal sera].", "content": "Qualitative and quantitative precipitin reactions are given of the polysaccharides K60, K61, K65, K67-69, K70, K71, K73, and K83, also of depyruvylated K1. As expected, the last reacts more strongly in antipneumococcal (anti-Pn) VIII and X than does intact K1. K65 and K67 precipitate much of the same large fraction of anti-PnXXIII as does K47, showing that K65 and K67 also possess lateral non-reducing end-groups of L-rhamnose. The massive reaction of K83 in anti-PnII confirms the chemically demonstrated non-reducing end-groups of D-glucuronic acid in the repeating unit, Such groups, or 1,2-linked D-glcA, will probably also be found in K71.", "contents": "[Cross reactions of higher type-specific capsular polysaccharides of Klebsiella in antipneumococcal sera]. Qualitative and quantitative precipitin reactions are given of the polysaccharides K60, K61, K65, K67-69, K70, K71, K73, and K83, also of depyruvylated K1. As expected, the last reacts more strongly in antipneumococcal (anti-Pn) VIII and X than does intact K1. K65 and K67 precipitate much of the same large fraction of anti-PnXXIII as does K47, showing that K65 and K67 also possess lateral non-reducing end-groups of L-rhamnose. The massive reaction of K83 in anti-PnII confirms the chemically demonstrated non-reducing end-groups of D-glucuronic acid in the repeating unit, Such groups, or 1,2-linked D-glcA, will probably also be found in K71."}
{"id": "PMID:15496", "title": "[Natural antiallergenic factors in bile].", "content": "Two groups of substances having an antihistaminic activity were found on purifying bovine bile. It has already been found that bile acids inhibit contraction of guinea pig ileum; another principle has been isolated which is one thousand times more active than the bile acids; this (these) substance(s)--SAN (\" substance antiallergique naturelle \")--seems to have more inhibitory effect on smooth muscle contraction induced by SRSA than histamine, acetylcholine, bradikinin and serotonin. SAN is also able to inhibit the Schultz-Dale reaction. These findings indicate that SAN could be a possible antiallergic agent.", "contents": "[Natural antiallergenic factors in bile]. Two groups of substances having an antihistaminic activity were found on purifying bovine bile. It has already been found that bile acids inhibit contraction of guinea pig ileum; another principle has been isolated which is one thousand times more active than the bile acids; this (these) substance(s)--SAN (\" substance antiallergique naturelle \")--seems to have more inhibitory effect on smooth muscle contraction induced by SRSA than histamine, acetylcholine, bradikinin and serotonin. SAN is also able to inhibit the Schultz-Dale reaction. These findings indicate that SAN could be a possible antiallergic agent."}
{"id": "PMID:15495", "title": "[Role of adherent cells in GVH induced immunosuppression].", "content": "Two different mechanisms seem to be involved. In early GVH there is apparently an amplification of a normal inhibitory function of a cells. In more advanced GVH immunosuppression seem to be caused by a GVH induced suppressive activity of A cells. Both activities seem to be mediated by soluble factors.", "contents": "[Role of adherent cells in GVH induced immunosuppression]. Two different mechanisms seem to be involved. In early GVH there is apparently an amplification of a normal inhibitory function of a cells. In more advanced GVH immunosuppression seem to be caused by a GVH induced suppressive activity of A cells. Both activities seem to be mediated by soluble factors."}
{"id": "PMID:15497", "title": "[Spleen reactivity after BCG treatement: test and strain dependency of the response].", "content": "According to the strain used, spleen cells from mice injected two weeks before with 3 mg BCG, when they are engaged in a graft-versus-host reaction show a decrease in reactivity (C57Bl/6or AKR), an increase (DBA/2, BALB/C or SJL/J) or no modification (CBA, C3H). The in vitro responsiveness to PHA and conA of the treated spleen cells was lower than controls for all the strains studied. However, nylon column purified T cells from BCG treated mice showed a dissociated response, being less stimulated than normal cells by PHA and more so by ConA.", "contents": "[Spleen reactivity after BCG treatement: test and strain dependency of the response]. According to the strain used, spleen cells from mice injected two weeks before with 3 mg BCG, when they are engaged in a graft-versus-host reaction show a decrease in reactivity (C57Bl/6or AKR), an increase (DBA/2, BALB/C or SJL/J) or no modification (CBA, C3H). The in vitro responsiveness to PHA and conA of the treated spleen cells was lower than controls for all the strains studied. However, nylon column purified T cells from BCG treated mice showed a dissociated response, being less stimulated than normal cells by PHA and more so by ConA."}
{"id": "PMID:15502", "title": "[Macrokinetic equations of pH effect on the growth of Actinomyces aureofaciens and biosynthesis of tetracycline].", "content": "The effect of pH on the culture respiration rate at different concentrations of glucose in the medium was studied. It was found that the hydrogen ions showed their effect irrespective of the subsrate concentration in the medium. In this connection a type of macrokinetic equations of the effect of pH on the growth and antibiotic biosynthesis was chosen. The constants of the model were determined.", "contents": "[Macrokinetic equations of pH effect on the growth of Actinomyces aureofaciens and biosynthesis of tetracycline]. The effect of pH on the culture respiration rate at different concentrations of glucose in the medium was studied. It was found that the hydrogen ions showed their effect irrespective of the subsrate concentration in the medium. In this connection a type of macrokinetic equations of the effect of pH on the growth and antibiotic biosynthesis was chosen. The constants of the model were determined."}
{"id": "PMID:15503", "title": "[Study of penicillin amidase from E. coli. pH-dependence of kinetic parameters of enzymatic hydrolysis of benzylpenicillin].", "content": "The authors studies pH-dependencies of the kinetic parameters (Vm, KM, Vm/KM) and constants of competitive inhibition by phenylacetic acid of penicillinamidase-catalyzed hydrolysis of benzylpenicillin. The experimental data are in agreement with the assumption according to which there are 3 equilibrium ionogenic forms of the enzyme and enzyme-substrate (or enzyme-inhibitor) complexes, i.e. acidic, neutral and alkaline, the neutral form being the only active form of the Michaelis complex. Values of pK in the ionogenic groups controlling interconversions of both the free enzyme (pK1 6.1 and pK2 7.6) and of the enzyme-substrate complex (pKa 6.1 and pK2 10.2 or the enzyzme-inhibitor complex (pK''1 6.1 and pK''2 9.5) were determined. From this and the previously published results it was concluded that the group with pK 6.1 was involved in the catalysis and the group with pK 10.2 in the maintenance of the active conformation of the active centre of penicillinamidase. The ionogenic group with pK 7.6 was apparently involved in the enzyme-substrate binding.", "contents": "[Study of penicillin amidase from E. coli. pH-dependence of kinetic parameters of enzymatic hydrolysis of benzylpenicillin]. The authors studies pH-dependencies of the kinetic parameters (Vm, KM, Vm/KM) and constants of competitive inhibition by phenylacetic acid of penicillinamidase-catalyzed hydrolysis of benzylpenicillin. The experimental data are in agreement with the assumption according to which there are 3 equilibrium ionogenic forms of the enzyme and enzyme-substrate (or enzyme-inhibitor) complexes, i.e. acidic, neutral and alkaline, the neutral form being the only active form of the Michaelis complex. Values of pK in the ionogenic groups controlling interconversions of both the free enzyme (pK1 6.1 and pK2 7.6) and of the enzyme-substrate complex (pKa 6.1 and pK2 10.2 or the enzyzme-inhibitor complex (pK''1 6.1 and pK''2 9.5) were determined. From this and the previously published results it was concluded that the group with pK 6.1 was involved in the catalysis and the group with pK 10.2 in the maintenance of the active conformation of the active centre of penicillinamidase. The ionogenic group with pK 7.6 was apparently involved in the enzyme-substrate binding."}
{"id": "PMID:15504", "title": "[Chromatographic separation of rifamycins on a thin sorbent thin layer].", "content": "A method of simultaneous separation of rifampicins O, S and rifamicin derivates S, SV in a thin layer of silica gel KSK No. 2 impregnated with acetate buffer, pH 4.6 in a solvent system chlorophorm-methanol (100:5) was developed. The minimum detectable amount of the compounds studied was 1--2gamma, when the coloured zones were estimated visually.", "contents": "[Chromatographic separation of rifamycins on a thin sorbent thin layer]. A method of simultaneous separation of rifampicins O, S and rifamicin derivates S, SV in a thin layer of silica gel KSK No. 2 impregnated with acetate buffer, pH 4.6 in a solvent system chlorophorm-methanol (100:5) was developed. The minimum detectable amount of the compounds studied was 1--2gamma, when the coloured zones were estimated visually."}
{"id": "PMID:15505", "title": "[Penicillin amidase from E. coli. A direct spectrophotometric method of determining the enzyme's activity].", "content": "A method for determination of the enzymatic activity of penicillinamidas (PA) based on spectrophotometric estimation of the stained product amount produced in hydrolysis of 4-phenylacetamido-2-nitrobenzoic acid (PANBA) catalyzed by the enzyme is proposed. Some physico-chemical properties of the substrate and the stained product were studied. The kinetic parameters of the PANABA enzymatic hydrolysis were determined. Catalytic activity of some enzyme products of PA of different purity levels was studied comparatively in reactions of PANBA and benzylpenicillin hydrolysis.", "contents": "[Penicillin amidase from E. coli. A direct spectrophotometric method of determining the enzyme's activity]. A method for determination of the enzymatic activity of penicillinamidas (PA) based on spectrophotometric estimation of the stained product amount produced in hydrolysis of 4-phenylacetamido-2-nitrobenzoic acid (PANBA) catalyzed by the enzyme is proposed. Some physico-chemical properties of the substrate and the stained product were studied. The kinetic parameters of the PANABA enzymatic hydrolysis were determined. Catalytic activity of some enzyme products of PA of different purity levels was studied comparatively in reactions of PANBA and benzylpenicillin hydrolysis."}
{"id": "PMID:15506", "title": "[Simplified liquid nutrient media for controlling antibiotic activity, the spectrum of their antibacterial action and the sensitivity of microorganisms].", "content": "Beaf-peptone broth and some of its modifications, one of which is a simple and in expensive one to a leser extent binding to antibiotics, such as penicillin, oxytetracycline and streptomycin and providing sufficient growth of the test microbes were used to determine the antibiotic activity with the methods of serial dilutions. The simple modification was recommended for practical use. The MIC of the antibiotics in the above simple medium was less than that in the control. The results of the antibiotic activity determination on both media coincided.", "contents": "[Simplified liquid nutrient media for controlling antibiotic activity, the spectrum of their antibacterial action and the sensitivity of microorganisms]. Beaf-peptone broth and some of its modifications, one of which is a simple and in expensive one to a leser extent binding to antibiotics, such as penicillin, oxytetracycline and streptomycin and providing sufficient growth of the test microbes were used to determine the antibiotic activity with the methods of serial dilutions. The simple modification was recommended for practical use. The MIC of the antibiotics in the above simple medium was less than that in the control. The results of the antibiotic activity determination on both media coincided."}
{"id": "PMID:15507", "title": "[Experimental study of a gentamicin aerosol].", "content": "The study of gentamicin aerosol showed its relative innocuousness: it did not inhibit the growth and development of young animals, did not induce pathological changes in the upper respiratory tract, kidneys, liver, heart and spleen on its prolonged use. Pathohistological examination revealed slight irritating effect of the gentamicin aerosol in the lungs after its use in a dose of 8 or 25 mg/kg for 6 weeks. A procedure for investigating the effect of the aerosol on the activity of the trachea ciliated epithelium of warm blooded animals was developed. The gentamicin aerosols prepared from solutions of different concentrations (1 to 50 mg/ml) induced ingibition of the ciliated epithelium function at average from 15 to 35 per cent which was associated with the solution acidity (pH 4.54 to 4.82). Such a decrease in the function of the ciliated epithelium due to the antibiotic aerosol use was a factor prolonging the antibiotic retention time in the respiratory organs. It was found that aqueous solutions of drugs used for inhalation, such as ephedrin, euphelin, dimedrol, N-acetyl-L-cystein and others had no effect on the activity of gentamicin and may be used with it in a form of aerosols.", "contents": "[Experimental study of a gentamicin aerosol]. The study of gentamicin aerosol showed its relative innocuousness: it did not inhibit the growth and development of young animals, did not induce pathological changes in the upper respiratory tract, kidneys, liver, heart and spleen on its prolonged use. Pathohistological examination revealed slight irritating effect of the gentamicin aerosol in the lungs after its use in a dose of 8 or 25 mg/kg for 6 weeks. A procedure for investigating the effect of the aerosol on the activity of the trachea ciliated epithelium of warm blooded animals was developed. The gentamicin aerosols prepared from solutions of different concentrations (1 to 50 mg/ml) induced ingibition of the ciliated epithelium function at average from 15 to 35 per cent which was associated with the solution acidity (pH 4.54 to 4.82). Such a decrease in the function of the ciliated epithelium due to the antibiotic aerosol use was a factor prolonging the antibiotic retention time in the respiratory organs. It was found that aqueous solutions of drugs used for inhalation, such as ephedrin, euphelin, dimedrol, N-acetyl-L-cystein and others had no effect on the activity of gentamicin and may be used with it in a form of aerosols."}
{"id": "PMID:15509", "title": "Effect of culture conditions on synthesis of L-asparaginase by Escherichia coli A-1.", "content": "The nutritional requirements and culture conditions affecting biosynthesis of L-asparaginase in a mutant of Escherichia coli HAP designated strain A-1 were studied. Asparaginase activity was increased by  the addition of L-glutamic acid, L-glutamine, or commercial-grade monosodium glutamate. The rate of enzyme synthesis was dependent on the interaction between the pH of the culture and the amount of oxygen dissolved in the medium. A critical oxygen transfer rate essential for asparaginase formation was identified, and a fermentation procedure is described in which enzyme synthesis is controlled by aeration rate. Enhancement of L-asparaginase activity by monosodium glutamate was inhibited by the presence of glucose, culture pH, chloramphenicol, and oxygen dissolved in the fermentation medium.", "contents": "Effect of culture conditions on synthesis of L-asparaginase by Escherichia coli A-1. The nutritional requirements and culture conditions affecting biosynthesis of L-asparaginase in a mutant of Escherichia coli HAP designated strain A-1 were studied. Asparaginase activity was increased by  the addition of L-glutamic acid, L-glutamine, or commercial-grade monosodium glutamate. The rate of enzyme synthesis was dependent on the interaction between the pH of the culture and the amount of oxygen dissolved in the medium. A critical oxygen transfer rate essential for asparaginase formation was identified, and a fermentation procedure is described in which enzyme synthesis is controlled by aeration rate. Enhancement of L-asparaginase activity by monosodium glutamate was inhibited by the presence of glucose, culture pH, chloramphenicol, and oxygen dissolved in the fermentation medium."}
{"id": "PMID:15510", "title": "Growth characteristics of a new methylomonad.", "content": "A methylomonad culture was isolated from pond water and examined as a potential source of single-cell protein. A medium containing magnesium sulfate, ammonium hydroxide, sodium phosphate, tap water, and methanol supported the growth of the isolate. Optimal growth conditions in batch cultures for the organism were: temperature, 30 to 33 degrees C; pH 7.1; and phosphate concentration, 0.015 M. The minimum doubling time obtained was 1.6 h. The specific growth rate in batch culture was dependent on the methanol concentration, reaching a maximum around 0.2% (wt/vol). Growth inhibition was apparent above 0.3% (wt/vol), and growth was completely inhibited above 4.6% (wt/vol) methanol. Although the inhibitory effect of formaldehyde on the specific growth rate was much greater than that of formate, the organism utilized formaldehyde, but not formate, as a sole carbon and energy source in batch cultures. The isolate was identified primarily by its inability to utilize any carbon source other than methanol and formaldehyde for growth. Although it is capable of rapid growth on methanol, the organism showed a very weak catalase activity. The amino acid content of the cells compared favorably with the reference levels for the essential amino acids specific by the Food and Agricultural Organization of the United Nations.", "contents": "Growth characteristics of a new methylomonad. A methylomonad culture was isolated from pond water and examined as a potential source of single-cell protein. A medium containing magnesium sulfate, ammonium hydroxide, sodium phosphate, tap water, and methanol supported the growth of the isolate. Optimal growth conditions in batch cultures for the organism were: temperature, 30 to 33 degrees C; pH 7.1; and phosphate concentration, 0.015 M. The minimum doubling time obtained was 1.6 h. The specific growth rate in batch culture was dependent on the methanol concentration, reaching a maximum around 0.2% (wt/vol). Growth inhibition was apparent above 0.3% (wt/vol), and growth was completely inhibited above 4.6% (wt/vol) methanol. Although the inhibitory effect of formaldehyde on the specific growth rate was much greater than that of formate, the organism utilized formaldehyde, but not formate, as a sole carbon and energy source in batch cultures. The isolate was identified primarily by its inability to utilize any carbon source other than methanol and formaldehyde for growth. Although it is capable of rapid growth on methanol, the organism showed a very weak catalase activity. The amino acid content of the cells compared favorably with the reference levels for the essential amino acids specific by the Food and Agricultural Organization of the United Nations."}
{"id": "PMID:15511", "title": "Association of hydrogen metabolism with methanogenesis in Lake Mendota sediments.", "content": "Lake Mendota sediments were studied to determine the role of H2 in sediment methanogenesis. H2 was generally not detectable in sediment. The addition of H2 to sediment significantly increased methanogenensis. The amount of methane produced was proportional to the concentration of hydrogen added. H2 addition stimulated the reduction of CO2 to methane, but did not significantly stimulate the conversion of methanol or the methyl position of acetate to methane. Various organic compounds also stimulated sediment methanogenesis. Formate, ethanol, and glucose were shown to serve as electron donors for CO2 reduction to methane. The addition of formate to sediment resulted in H2 evolution. H2 was not deith the phenomenon of interspecies hydrogen transfer. The results indicate that hydrogen is an important intermediate and a rate-limiting factor in sediment methanogenesis.", "contents": "Association of hydrogen metabolism with methanogenesis in Lake Mendota sediments. Lake Mendota sediments were studied to determine the role of H2 in sediment methanogenesis. H2 was generally not detectable in sediment. The addition of H2 to sediment significantly increased methanogenensis. The amount of methane produced was proportional to the concentration of hydrogen added. H2 addition stimulated the reduction of CO2 to methane, but did not significantly stimulate the conversion of methanol or the methyl position of acetate to methane. Various organic compounds also stimulated sediment methanogenesis. Formate, ethanol, and glucose were shown to serve as electron donors for CO2 reduction to methane. The addition of formate to sediment resulted in H2 evolution. H2 was not deith the phenomenon of interspecies hydrogen transfer. The results indicate that hydrogen is an important intermediate and a rate-limiting factor in sediment methanogenesis."}
{"id": "PMID:15512", "title": "Media for identification of Gibberella zeae and production of F-2-(Zearalenone).", "content": "Media are described for the isolaton of Fusarium graminearum in the perithecial state, Gibberella zeae, and for the production of F-2 (zearalenone) by Fusarium species. On soil extract-corn meal agar isolated medium, G. Zeae produced perithecia in 9 to 14 days under a 12-h photoperiod. Species of Fusarium were screened for F-2 production on a liquid medium. From strains that produced F-2, the yields, from stationary cultures of G. zeae and F. culmorum after 12 days of incubation, ranged from 22 to 86 mg/liter. Three strains produced no F-2. Glumatic acid, starch, yeast extract,and the proper ratio of medium volume-to-flask volume were necessary for F-2 synthesis.", "contents": "Media for identification of Gibberella zeae and production of F-2-(Zearalenone). Media are described for the isolaton of Fusarium graminearum in the perithecial state, Gibberella zeae, and for the production of F-2 (zearalenone) by Fusarium species. On soil extract-corn meal agar isolated medium, G. Zeae produced perithecia in 9 to 14 days under a 12-h photoperiod. Species of Fusarium were screened for F-2 production on a liquid medium. From strains that produced F-2, the yields, from stationary cultures of G. zeae and F. culmorum after 12 days of incubation, ranged from 22 to 86 mg/liter. Three strains produced no F-2. Glumatic acid, starch, yeast extract,and the proper ratio of medium volume-to-flask volume were necessary for F-2 synthesis."}
{"id": "PMID:15524", "title": "Wilm's tumour, hypospadias, and cryptorchidism in twins.", "content": "Twin boys, both of whom had hypospadias and bilateral cryptorchidism, each developed a left-sided Wilms's tumour. The first twin was found to have an advanced multifocal tumour at the age of 15 months and died with local recurrence and pulmonary metastases. The diagnosis was made in the second twin one month later and at nephrectomy the tumour was found to be encapsulated without metastases; he is disease-free 12-years later. Although the histological appearances were similar in each twin, the tumours did not develop at the same rate and did not show the 'mirror-image' pattern suggested for embryonal tumours in identical twins.", "contents": "Wilm's tumour, hypospadias, and cryptorchidism in twins. Twin boys, both of whom had hypospadias and bilateral cryptorchidism, each developed a left-sided Wilms's tumour. The first twin was found to have an advanced multifocal tumour at the age of 15 months and died with local recurrence and pulmonary metastases. The diagnosis was made in the second twin one month later and at nephrectomy the tumour was found to be encapsulated without metastases; he is disease-free 12-years later. Although the histological appearances were similar in each twin, the tumours did not develop at the same rate and did not show the 'mirror-image' pattern suggested for embryonal tumours in identical twins."}
{"id": "PMID:15525", "title": "Effects of beta-adrenoceptor blocking agents, pindolol, alprenolol and practolol on blood pressure and heart rate in conscious renal hypertensive dogs.", "content": "The effects of pindolol, 10 mg/kg, alprenolol, 50 mg/kg, and practolol, 50 mg/kg, given by mouth, on blood pressure and heart rate were investigated over a 24-hr period in 5 conscious renal hypertensive dogs, using a cross-over design. Pindolol and alprenolol caused significant falls in blood pressure which averaged 22 mm Hg (at 3-hr after p.o. administration) and 20 mm Hg (at 3-hr). However, practolol failed to produce any significant changes in blood pressure. Heart rate increased by 67 beats/min (at 1-hr) and 39 beats/min (at 3-hr) after pindolol and alprenolol, respectively, but did not show any significant increase when practolol was given orally. The pindolol-induced tachycardia and hypotension were not suppressed significantly by propranolol (1 mg/kg i.v.) which blocked completely the tachycardia and hypotension induced by isoprenaline (3 mg/kg p.o.). The hypotension and tachycardia observed after oral administration of D-32 (50 mg/kg) or after intravenous infusion of p-OH D-32 (1 mg/kg per min for 5 min) were also not modified significantly by propranolol (1 mg/kg i.v.). Based on these results and other published data, mechanisms pertaining to the hypotension exerted by beta-adrenoceptor blocking agents were discussed.", "contents": "Effects of beta-adrenoceptor blocking agents, pindolol, alprenolol and practolol on blood pressure and heart rate in conscious renal hypertensive dogs. The effects of pindolol, 10 mg/kg, alprenolol, 50 mg/kg, and practolol, 50 mg/kg, given by mouth, on blood pressure and heart rate were investigated over a 24-hr period in 5 conscious renal hypertensive dogs, using a cross-over design. Pindolol and alprenolol caused significant falls in blood pressure which averaged 22 mm Hg (at 3-hr after p.o. administration) and 20 mm Hg (at 3-hr). However, practolol failed to produce any significant changes in blood pressure. Heart rate increased by 67 beats/min (at 1-hr) and 39 beats/min (at 3-hr) after pindolol and alprenolol, respectively, but did not show any significant increase when practolol was given orally. The pindolol-induced tachycardia and hypotension were not suppressed significantly by propranolol (1 mg/kg i.v.) which blocked completely the tachycardia and hypotension induced by isoprenaline (3 mg/kg p.o.). The hypotension and tachycardia observed after oral administration of D-32 (50 mg/kg) or after intravenous infusion of p-OH D-32 (1 mg/kg per min for 5 min) were also not modified significantly by propranolol (1 mg/kg i.v.). Based on these results and other published data, mechanisms pertaining to the hypotension exerted by beta-adrenoceptor blocking agents were discussed."}
{"id": "PMID:15526", "title": "Selective activation of cardiovascular adenylate cyclase in vivo.", "content": "Cyclic AMP levels were measured in cardiac and vascular tissues removed from pentobarbitone-anesthetized rats pretreated with theophylline 45 mg/kg i.p. Noradrenaline, 20 microng/kg i.v., increased cardiac but not vascular cyclic AMP levels; this selective effect of noradrenaline was not altered by pretreatment with phenoxybenzamine, 1 mg/kg i.v. Tazolol, 120 microng/kg i.v., selectively increased cardiac cyclic AMP levels whereas fenoterol, 15 microng/kg i.v., selectively increased vascular cyclic AMP levels. The results suggest that adenylate cyclase activation in cardiac and vascular tissued in vivo is mediated by beta adrenoceptors which consist of different subtypes.", "contents": "Selective activation of cardiovascular adenylate cyclase in vivo. Cyclic AMP levels were measured in cardiac and vascular tissues removed from pentobarbitone-anesthetized rats pretreated with theophylline 45 mg/kg i.p. Noradrenaline, 20 microng/kg i.v., increased cardiac but not vascular cyclic AMP levels; this selective effect of noradrenaline was not altered by pretreatment with phenoxybenzamine, 1 mg/kg i.v. Tazolol, 120 microng/kg i.v., selectively increased cardiac cyclic AMP levels whereas fenoterol, 15 microng/kg i.v., selectively increased vascular cyclic AMP levels. The results suggest that adenylate cyclase activation in cardiac and vascular tissued in vivo is mediated by beta adrenoceptors which consist of different subtypes."}
{"id": "PMID:15527", "title": "Comparative subcutaneous absorption of local anesthetics: lidocaine, procaine and tetracaine.", "content": "The pH partition hypothesis was applied to the absorption of ionizable local anesthetic amines through the subcutaneous (s.c.) route. Solutions of lidocaine hydrochloride (LHCl), procaine hydrochloride (PHCl) and tetracaine hydrochloride (THCl) at various pH were implanted on s.c. animal tissue through a glass absorption cell. The s.c. absorption of these drugs was evaluated from the clearances' slopes evolved by determination of the drugs' concentrations in the cell at definite intervals. The higher the pH level, these conjugated bases become more unionized and lipid partitioned resulting in increased rates of s.c. absorption. The extent of unionization is governed by the pka of each of these drugs; at the high feasible pH--procaine which is least unionized--its s.c. absorption rate is nearly a third of that of lidocaine or tetracaine. The pH effect on s.c. absorption of local anesthetics was substantiated by estimation of lethal time50 (LT50) in mice.", "contents": "Comparative subcutaneous absorption of local anesthetics: lidocaine, procaine and tetracaine. The pH partition hypothesis was applied to the absorption of ionizable local anesthetic amines through the subcutaneous (s.c.) route. Solutions of lidocaine hydrochloride (LHCl), procaine hydrochloride (PHCl) and tetracaine hydrochloride (THCl) at various pH were implanted on s.c. animal tissue through a glass absorption cell. The s.c. absorption of these drugs was evaluated from the clearances' slopes evolved by determination of the drugs' concentrations in the cell at definite intervals. The higher the pH level, these conjugated bases become more unionized and lipid partitioned resulting in increased rates of s.c. absorption. The extent of unionization is governed by the pka of each of these drugs; at the high feasible pH--procaine which is least unionized--its s.c. absorption rate is nearly a third of that of lidocaine or tetracaine. The pH effect on s.c. absorption of local anesthetics was substantiated by estimation of lethal time50 (LT50) in mice."}
{"id": "PMID:15528", "title": "Acidostability of speroplasts prepared from Thiobacillus thiooxidans.", "content": "Thiobacillus thiooxidans was acidostable even in the absence of its respiratory substrate, elementary sulfur. This suggests that the acidostability of the bacterium was enery-independent. The organism was subjected to osmotic shock with 0.75 M sucrose at 0 degrees C and then treated with snail intestinal juice in the presence of 0.3 M sucrose. The decrease in the optical density of the sample thus prepared on dilution with deionized water and electron microscopic observation of the sample showed that spheroplasts were formed from the bacterium by this procedure. Spheroplasts were able to respire sulfur and their respiratory activity was acidostable. Spheroplasts, when treated with Nagase, proteolytic enzyme, lost their acidostability, and some protein components disappeared from the membrane fraction. This suggests that the acidostability of the bacterium may be related to protein conponents of the membrane.", "contents": "Acidostability of speroplasts prepared from Thiobacillus thiooxidans. Thiobacillus thiooxidans was acidostable even in the absence of its respiratory substrate, elementary sulfur. This suggests that the acidostability of the bacterium was enery-independent. The organism was subjected to osmotic shock with 0.75 M sucrose at 0 degrees C and then treated with snail intestinal juice in the presence of 0.3 M sucrose. The decrease in the optical density of the sample thus prepared on dilution with deionized water and electron microscopic observation of the sample showed that spheroplasts were formed from the bacterium by this procedure. Spheroplasts were able to respire sulfur and their respiratory activity was acidostable. Spheroplasts, when treated with Nagase, proteolytic enzyme, lost their acidostability, and some protein components disappeared from the membrane fraction. This suggests that the acidostability of the bacterium may be related to protein conponents of the membrane."}
{"id": "PMID:15529", "title": "Effect of external factors on phototaxis of Chlamydomonas reinhardtii. II. Charbon dioxide, oxygen and pH.", "content": "1. The effects of carbon dioxide, oxygen and pH on the inversion intensity of phototaxis of Chlamydomonas reinhardtii have been investigated. 2. With decreasing with CO2 tension the inversion intensity is decreased. 3. The gassing with CO2 can be substituted by hydrogencarbonate only to a small extent (20%). On the other hand, the effect of decreasing CO2 tension can be prevented also only in part by adjusting the pH to about 6.5-7.0. Thus the effect of CO2 on the inversion intensity of phototaxis is obviously a composite of a true CO2 effect and an effect of the concomitant pH change. 4. Oxygen has only a slight effect. In presence of oxygen (air) the phototactic reaction values are somewhat lower than in its absence. 5. Under certain conditions circadian rhythms seem to be initiated by changing oxygen as well as CO2 tensions. 6. Based on these results some contradictory results of older investigations are discussed.", "contents": "Effect of external factors on phototaxis of Chlamydomonas reinhardtii. II. Charbon dioxide, oxygen and pH. 1. The effects of carbon dioxide, oxygen and pH on the inversion intensity of phototaxis of Chlamydomonas reinhardtii have been investigated. 2. With decreasing with CO2 tension the inversion intensity is decreased. 3. The gassing with CO2 can be substituted by hydrogencarbonate only to a small extent (20%). On the other hand, the effect of decreasing CO2 tension can be prevented also only in part by adjusting the pH to about 6.5-7.0. Thus the effect of CO2 on the inversion intensity of phototaxis is obviously a composite of a true CO2 effect and an effect of the concomitant pH change. 4. Oxygen has only a slight effect. In presence of oxygen (air) the phototactic reaction values are somewhat lower than in its absence. 5. Under certain conditions circadian rhythms seem to be initiated by changing oxygen as well as CO2 tensions. 6. Based on these results some contradictory results of older investigations are discussed."}
{"id": "PMID:15530", "title": "Penicillinase (beta-lactamase) formation by blue-green algae.", "content": "Beta-Lactamase (penicillinase) activity was found in a number of strains of blue-green algea. In some cases, this enzyme permitted algae to overcome the inhibitory effects of penicillin. Production and localization of beta-lactamase were studied in a unicellular species, Coccochloris elabens (strain 7003), and in a filamentous, nitrogen-fixing Anabaena species (strain 7120). When cells were grown in a neutral medium with NaNO3 as N source, the pH rose during growth; at a pH of about 10, most of the enzyme was expressed equally well in intact or disrupted cells. If the pH was kept near neutrality during growth by gassing with CO2 in N2 or by growth under conditions of N2 fixation, the enzyme remained cell-bound and cryptic for most of the growth phase, being measurable only after cells were disrupted. The enzymes from strains 7003 and 7120 had greater activity on benzyl penicillin and other penicillins than on cephalosporins. Some differences were observed in the \"substrate proliles\" of penicillinases from the two strains against different penicillins.", "contents": "Penicillinase (beta-lactamase) formation by blue-green algae. Beta-Lactamase (penicillinase) activity was found in a number of strains of blue-green algea. In some cases, this enzyme permitted algae to overcome the inhibitory effects of penicillin. Production and localization of beta-lactamase were studied in a unicellular species, Coccochloris elabens (strain 7003), and in a filamentous, nitrogen-fixing Anabaena species (strain 7120). When cells were grown in a neutral medium with NaNO3 as N source, the pH rose during growth; at a pH of about 10, most of the enzyme was expressed equally well in intact or disrupted cells. If the pH was kept near neutrality during growth by gassing with CO2 in N2 or by growth under conditions of N2 fixation, the enzyme remained cell-bound and cryptic for most of the growth phase, being measurable only after cells were disrupted. The enzymes from strains 7003 and 7120 had greater activity on benzyl penicillin and other penicillins than on cephalosporins. Some differences were observed in the \"substrate proliles\" of penicillinases from the two strains against different penicillins."}
{"id": "PMID:15531", "title": "Metabolic regulation of the glucose-6-phosphate dehydrogenase from Paracoccus denitrifcans grown on glucose/nitrate.", "content": "Glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate : NADP+ L-oxidoreductase EC 1.1.1.49) isolated from Paracoccus denitrificans grown on glucose/nitrate exhibits both NAD+-and NADP+- linked activities. Both activities have a pH optimum of pH 9.6 (Glycine/NaOH buffer) and neither demonstrates a Mg2+ requirement. Kinetics for both NAD(P)+ and glucose-6-phosphate were investigated. Phosphoenolpyruvate inhibits both activities in a competitive manner with respect to glucose-6-phosphate. ATP inhibits the NAD+-linked activity competitively with respect to glucose-6-phosphate but has no effect on the NADP+-linked activity. Neither of the two activities are inhibited by 100 muM NADH but both are inhibited by NADPH. The NAD+-linked activity is far more sensitive to inhibition by NADPH than the NADP+-linked activity.", "contents": "Metabolic regulation of the glucose-6-phosphate dehydrogenase from Paracoccus denitrifcans grown on glucose/nitrate. Glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate : NADP+ L-oxidoreductase EC 1.1.1.49) isolated from Paracoccus denitrificans grown on glucose/nitrate exhibits both NAD+-and NADP+- linked activities. Both activities have a pH optimum of pH 9.6 (Glycine/NaOH buffer) and neither demonstrates a Mg2+ requirement. Kinetics for both NAD(P)+ and glucose-6-phosphate were investigated. Phosphoenolpyruvate inhibits both activities in a competitive manner with respect to glucose-6-phosphate. ATP inhibits the NAD+-linked activity competitively with respect to glucose-6-phosphate but has no effect on the NADP+-linked activity. Neither of the two activities are inhibited by 100 muM NADH but both are inhibited by NADPH. The NAD+-linked activity is far more sensitive to inhibition by NADPH than the NADP+-linked activity."}
{"id": "PMID:15532", "title": "Cellular proteases increased in paramyxovirus (Sendai virus) carrier cells possibly responsible for enhanced formation of cowpox virus-specific cell surface antigen.", "content": "Cowpox virus (CPV) growth and its S-ag (cell surface antigen) formation  in HVJ (Sendai virus) carrier cells pre-treated with Actinomycin D or Puromycin were not affected as much as those in parent cells. These suggest the different cellular functions of carrier cells. The activity of carrier cell extracts causing a characteristic degradation of CPV reacted with them in vitro disappeared after the pre-incubation of extracts with hemoglobin or casein. Measurements of cellular protease activities including lysosomal enzymes demonstrated significant increases in the carrier cell extracts compared to those in parent cells; The CPV, thus reacted in vitro with the extracts or lysosomal fraction from carrier cells, acquired more rapidly and markedly the enhanced ability of S-ag formation parallel to virus infectivity alteration in the reaction. These results indicate that the enhancement of CPV S-ag formation in the HVJ carrier cells may be due to their increased cellular enzymes, possibly proteolytic ones, capable of promoting the first step of CPV uncoating or degradation in the cells.", "contents": "Cellular proteases increased in paramyxovirus (Sendai virus) carrier cells possibly responsible for enhanced formation of cowpox virus-specific cell surface antigen. Cowpox virus (CPV) growth and its S-ag (cell surface antigen) formation  in HVJ (Sendai virus) carrier cells pre-treated with Actinomycin D or Puromycin were not affected as much as those in parent cells. These suggest the different cellular functions of carrier cells. The activity of carrier cell extracts causing a characteristic degradation of CPV reacted with them in vitro disappeared after the pre-incubation of extracts with hemoglobin or casein. Measurements of cellular protease activities including lysosomal enzymes demonstrated significant increases in the carrier cell extracts compared to those in parent cells; The CPV, thus reacted in vitro with the extracts or lysosomal fraction from carrier cells, acquired more rapidly and markedly the enhanced ability of S-ag formation parallel to virus infectivity alteration in the reaction. These results indicate that the enhancement of CPV S-ag formation in the HVJ carrier cells may be due to their increased cellular enzymes, possibly proteolytic ones, capable of promoting the first step of CPV uncoating or degradation in the cells."}
{"id": "PMID:15535", "title": "Overlay dentures. Philosophy and practice. II.", "content": "The practical stages in the construction of mandibular overlay dentures, with and without precision attachment anchors, are described and illustrated in detail. The importance of post-insertion maintenance, continuing effective oral hygiene and patient care, as a prerequisite for a successful overlay denture experience, is emphasized.", "contents": "Overlay dentures. Philosophy and practice. II. The practical stages in the construction of mandibular overlay dentures, with and without precision attachment anchors, are described and illustrated in detail. The importance of post-insertion maintenance, continuing effective oral hygiene and patient care, as a prerequisite for a successful overlay denture experience, is emphasized."}
{"id": "PMID:15536", "title": "Fatty liver and kidney syndrome in chicks. II. Biochemical role of biotin.", "content": "The role of biotin-dependent enzymes in the fatty liver and kidney syndrome of young chicks was studied. Under conditions of a marginal deficiency of dietary biotin, the level of biotin in the liver has differing effects on the activities of two biotin-dependent enzymes, pyruvate carboxylase and acetyl-CoA carboxylase. The activity of acetyl-CoA carboxylase is increased, but when the dietary deficiency of biotin produces biotin levels which are below 0-8 mug/g of liver, the activity of pyruvate carboxylase may be insufficient to completely metabolize pyruvate via gluconeogenesis. There is an increase in liver size and in the activities of enzymes involved in alternate pathways for the removal of pyruvate. Blood lactate accumulates and there is increased synthesis of fatty acids, and an accumulation of palmitoleic acid; these steps are accomplished by increased activities of at least the following enzymes: acetyl-CoA carboxylase, malate dehydrogenase (decarboxylating) (NADP+) and the desaturase enzyme. When the biotin level is below 0-35 mug/g of liver and the chick is subjected to a stress, physiological defence mechanisms of the chick may be inadequate to maintain homeostasis and they finally collapse, resulting in accumulation of triacylglycerol in the liver and blood; the chick is unable to maintain blood glucose levels and death occurs, often only a few hours after the imposition of the stress.", "contents": "Fatty liver and kidney syndrome in chicks. II. Biochemical role of biotin. The role of biotin-dependent enzymes in the fatty liver and kidney syndrome of young chicks was studied. Under conditions of a marginal deficiency of dietary biotin, the level of biotin in the liver has differing effects on the activities of two biotin-dependent enzymes, pyruvate carboxylase and acetyl-CoA carboxylase. The activity of acetyl-CoA carboxylase is increased, but when the dietary deficiency of biotin produces biotin levels which are below 0-8 mug/g of liver, the activity of pyruvate carboxylase may be insufficient to completely metabolize pyruvate via gluconeogenesis. There is an increase in liver size and in the activities of enzymes involved in alternate pathways for the removal of pyruvate. Blood lactate accumulates and there is increased synthesis of fatty acids, and an accumulation of palmitoleic acid; these steps are accomplished by increased activities of at least the following enzymes: acetyl-CoA carboxylase, malate dehydrogenase (decarboxylating) (NADP+) and the desaturase enzyme. When the biotin level is below 0-35 mug/g of liver and the chick is subjected to a stress, physiological defence mechanisms of the chick may be inadequate to maintain homeostasis and they finally collapse, resulting in accumulation of triacylglycerol in the liver and blood; the chick is unable to maintain blood glucose levels and death occurs, often only a few hours after the imposition of the stress."}
{"id": "PMID:15537", "title": "Changes in plasma enzyme concentrations following intramuscular injections and gastroscopy.", "content": "The effects of intramuscular injections on plasma creatine kinase (CK), aspartate amino-transferase, lactate dehydrogenase, and hydroxybutyrate dehydrogenase concentrations were examined in 19 patients given intramuscular premedication for gastroscopy, and 18 patients given other intramuscular injections. Only CK concentrations showed significant increases which were as high as four times the upper limit of normal, and affected a maximum of 51% of patients at 12 hours after the first injection. Elevated CK concentrations persisted for up to 72 hours, and followed injections of diazepam, various antibiotics, and the combination of a narcotic analgesic with atropine. Gastroscopy did not appear to increase plasma enzyme concentrations in six patients who were given intravenous premedication. The significance of these findings to the diagnosis of myocardial infarction is discussed.", "contents": "Changes in plasma enzyme concentrations following intramuscular injections and gastroscopy. The effects of intramuscular injections on plasma creatine kinase (CK), aspartate amino-transferase, lactate dehydrogenase, and hydroxybutyrate dehydrogenase concentrations were examined in 19 patients given intramuscular premedication for gastroscopy, and 18 patients given other intramuscular injections. Only CK concentrations showed significant increases which were as high as four times the upper limit of normal, and affected a maximum of 51% of patients at 12 hours after the first injection. Elevated CK concentrations persisted for up to 72 hours, and followed injections of diazepam, various antibiotics, and the combination of a narcotic analgesic with atropine. Gastroscopy did not appear to increase plasma enzyme concentrations in six patients who were given intravenous premedication. The significance of these findings to the diagnosis of myocardial infarction is discussed."}
{"id": "PMID:15538", "title": "Effects of changes in pH of bath fluid on isolated guinea pig ileum preparation.", "content": "The effects of changes in the pH of Tyrode's solution on the responses of isolated guinea pig ileum preparation to acetylcholine and histamine were studied. At higher levels of pH (increased alkalinity), the responses of the tissue to both acetylcholine and histamine were increased. At lower pH levels (increased acidity), the response of the tissue to acetylcholine was increased but that to histamine was reduced.", "contents": "Effects of changes in pH of bath fluid on isolated guinea pig ileum preparation. The effects of changes in the pH of Tyrode's solution on the responses of isolated guinea pig ileum preparation to acetylcholine and histamine were studied. At higher levels of pH (increased alkalinity), the responses of the tissue to both acetylcholine and histamine were increased. At lower pH levels (increased acidity), the response of the tissue to acetylcholine was increased but that to histamine was reduced."}
{"id": "PMID:15539", "title": "Glycosidases from the culture medium of Physarum polycephalum.", "content": "Eight exo-glycosidase activities were detected in the axenic culture medium of the myxomycete, Physarum polycephalum. The secretion of each enzyme examined followed the growth curve and continued during the stationary phase after the cessation of growth. Two or more forms of each enzyme were detected after electrophoretic separation. The beta-N-acetyl-D-hexosaminidase activity was readily separated into its two electrophoretic forms, X and Y, which were purified 145- and 306-fold respectively. These beta-N-acetyl-D-hexosaminidases had several similar characteristics. Evidence is presented that the major electrophoretic form of alpha-D-galactosidase is heterogeneous. The possible functions of extracellular glycosidases in teir occurrence and properties.", "contents": "Glycosidases from the culture medium of Physarum polycephalum. Eight exo-glycosidase activities were detected in the axenic culture medium of the myxomycete, Physarum polycephalum. The secretion of each enzyme examined followed the growth curve and continued during the stationary phase after the cessation of growth. Two or more forms of each enzyme were detected after electrophoretic separation. The beta-N-acetyl-D-hexosaminidase activity was readily separated into its two electrophoretic forms, X and Y, which were purified 145- and 306-fold respectively. These beta-N-acetyl-D-hexosaminidases had several similar characteristics. Evidence is presented that the major electrophoretic form of alpha-D-galactosidase is heterogeneous. The possible functions of extracellular glycosidases in teir occurrence and properties."}
{"id": "PMID:15540", "title": "A pulse-radiolysis study of the catalytic mechanism of the iron-containing superoxide dismutase from Photobacterium leiognathi.", "content": "The mechanism of the enzymic reaction of an iron-containing superoxide dismutase purified from the marine bacterium Photobacterium leiognathi was studied by using pulse radiolysis. Measurements of activity were done with two different preparations of enzyme containing either 1.6 or 1.15 g-atom of iron/mol. In both cases, identical values of the second-order rate constant for reaction between superoxide dismutase and the superoxide ion in the pH range 6.2-9.0 (k=5.5 X 10(8) M-1-S-1 at pH 8.0) were found. As with the bovine erythrocuprein, there was no evidence for substrate saturation. The effects of reducing agents (H2O2, sodium ascorbate or CO2 radicals) on the visible and the electron-paramagnetic-resonance spectra of the superoxide dismutase containing 1.6 g-atom of ferric iron/mol indicate that this enzyme contains two different types of iron. Turnover experiments demonstrate that only that fraction of the ferric iron that is reduced by H2O2 is involved in the catalysis, being alternately oxidized and reduced by O2; both the oxidation and the reduction steps have a rate constant equal to that measured under turnover conditions. These results are interpreted by assuming that the superoxide dismutase isolated from the organism contains 1 g-atom of catalytic iron/mol and a variable amount of non-catalytic iron. This interpretation is discused in relation to the stoicheiometry reported for iron-containing superoxide dismutases prepared from several other organisms.", "contents": "A pulse-radiolysis study of the catalytic mechanism of the iron-containing superoxide dismutase from Photobacterium leiognathi. The mechanism of the enzymic reaction of an iron-containing superoxide dismutase purified from the marine bacterium Photobacterium leiognathi was studied by using pulse radiolysis. Measurements of activity were done with two different preparations of enzyme containing either 1.6 or 1.15 g-atom of iron/mol. In both cases, identical values of the second-order rate constant for reaction between superoxide dismutase and the superoxide ion in the pH range 6.2-9.0 (k=5.5 X 10(8) M-1-S-1 at pH 8.0) were found. As with the bovine erythrocuprein, there was no evidence for substrate saturation. The effects of reducing agents (H2O2, sodium ascorbate or CO2 radicals) on the visible and the electron-paramagnetic-resonance spectra of the superoxide dismutase containing 1.6 g-atom of ferric iron/mol indicate that this enzyme contains two different types of iron. Turnover experiments demonstrate that only that fraction of the ferric iron that is reduced by H2O2 is involved in the catalysis, being alternately oxidized and reduced by O2; both the oxidation and the reduction steps have a rate constant equal to that measured under turnover conditions. These results are interpreted by assuming that the superoxide dismutase isolated from the organism contains 1 g-atom of catalytic iron/mol and a variable amount of non-catalytic iron. This interpretation is discused in relation to the stoicheiometry reported for iron-containing superoxide dismutases prepared from several other organisms."}
{"id": "PMID:15541", "title": "A study of the ionic properties of the essential histidine residue of yeast alcohol dehydrogenase in complexes of the enzyme with its coenzymes and substrates.", "content": "1. Initial-rate studies of the reduction of acetaldehyde by NADH, catalysed by yeast alcohol dehydrogenase, were performed at pH 4.9 and 9.9, in various buffers, at 25 degrees C. The results are discussed in terms of the mechanism previously proposed for the pH range 5.9-8.9 [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. 2. Acetaldehyde forms a u.v.-absorbing complex with glycine. This was shown not to affect the results of kinetic experiments under the conditions used in this and earlier work. 3. The variation with pH of the dissociation constant for the enzyme-NADH complex, calculated from the initial-rate data, indicates that the enzyme possesses a group with pK7.1 in the free enzyme and pK8.7 in the complex. 4. The pH-dependences of the second-order rate constants for inactivation of the enzyme by diethyl pyrocarbonate were determined for the free enzymes (pK7.1), the enzyme-NAD+ complex (pK approx. 7.1) and the enzyme-NADH complex (pK approx. 8.4). The essential histidine residue may therefore be the group involved in formation and dissociation of the enzyme-NADH complex. 5. Estimates of the rate constant for reaction of acetaldehyde with the enzyme-NADH complex indicate that acetaldehyde may combine only when the essential histidine residue is protonated. The dissociation constants for butan-1-ol and propan-2-ol, calculated on the basis of earlier kinetic data, are, however, independent of pH. 6. The results obtained are discussed in relation to the role of the essential histidine residue in the mechanism of formation of binary and ternary complexes of the enzyme with its coenzymes and substrates.", "contents": "A study of the ionic properties of the essential histidine residue of yeast alcohol dehydrogenase in complexes of the enzyme with its coenzymes and substrates. 1. Initial-rate studies of the reduction of acetaldehyde by NADH, catalysed by yeast alcohol dehydrogenase, were performed at pH 4.9 and 9.9, in various buffers, at 25 degrees C. The results are discussed in terms of the mechanism previously proposed for the pH range 5.9-8.9 [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. 2. Acetaldehyde forms a u.v.-absorbing complex with glycine. This was shown not to affect the results of kinetic experiments under the conditions used in this and earlier work. 3. The variation with pH of the dissociation constant for the enzyme-NADH complex, calculated from the initial-rate data, indicates that the enzyme possesses a group with pK7.1 in the free enzyme and pK8.7 in the complex. 4. The pH-dependences of the second-order rate constants for inactivation of the enzyme by diethyl pyrocarbonate were determined for the free enzymes (pK7.1), the enzyme-NAD+ complex (pK approx. 7.1) and the enzyme-NADH complex (pK approx. 8.4). The essential histidine residue may therefore be the group involved in formation and dissociation of the enzyme-NADH complex. 5. Estimates of the rate constant for reaction of acetaldehyde with the enzyme-NADH complex indicate that acetaldehyde may combine only when the essential histidine residue is protonated. The dissociation constants for butan-1-ol and propan-2-ol, calculated on the basis of earlier kinetic data, are, however, independent of pH. 6. The results obtained are discussed in relation to the role of the essential histidine residue in the mechanism of formation of binary and ternary complexes of the enzyme with its coenzymes and substrates."}
{"id": "PMID:15542", "title": "The use of gadolinium as a probe in the Fc region of a homogeneous anti-(type-III pneumococcal polysaccharide) antibody.", "content": "The binding of gadolinium [Gd(III)] to a homogeneous rabbit anti-(type-III pneumococcal polysaccharide) IgG (immunoglobulin G) and its Fab (N-terminal half of heavy and light chain) and Fc (C-terminal half of heavy-chain dimer) fragments was demonstrated by measurements of solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 the binding of Gd(III) to the Fc fragment is much tighter (KD approx. 5 micronM) than binding to the Fab fragment (KD approx. 250 micronM). The binding of Gd(III) to the whole IgG molecule (KD approx. 4 micronM) is very similar to that for the Fc fragment alone. This specificity of binding to the Fc region allows the use of Gd(III) as a probe of the Fc conformation. The environment of the Gd(III) in the Fc region of whole IgG is not affected by the presence of octasaccharide derived by hydrolysis of type-III pneumococcal polysaccharide, but the corresponding 28-unit saccharide does cause detectable changes. The addition of 16-unit saccharide to anti-(SIII polysaccharide) IgG in the presence of Gd(III) does not change the solvent water proton relaxation rate, although aggregation does occur. The effects of the 28-unit saccharide may be explained therefore by a change in the tumbling time of the IgG. From a study of the effect of various antigen/antibody ratios, it is concluded that the 28-unit-saccharide-induced changes in the Gd(III) environment in the Fc region are caused by the specific geometrical structure of the antigen-antibody complexes formed, and not simply by occupancy of the combining sites on the antibody.", "contents": "The use of gadolinium as a probe in the Fc region of a homogeneous anti-(type-III pneumococcal polysaccharide) antibody. The binding of gadolinium [Gd(III)] to a homogeneous rabbit anti-(type-III pneumococcal polysaccharide) IgG (immunoglobulin G) and its Fab (N-terminal half of heavy and light chain) and Fc (C-terminal half of heavy-chain dimer) fragments was demonstrated by measurements of solvent-water proton relaxation rates in the appropriate Gd(III) solutions. At pH 5.5 the binding of Gd(III) to the Fc fragment is much tighter (KD approx. 5 micronM) than binding to the Fab fragment (KD approx. 250 micronM). The binding of Gd(III) to the whole IgG molecule (KD approx. 4 micronM) is very similar to that for the Fc fragment alone. This specificity of binding to the Fc region allows the use of Gd(III) as a probe of the Fc conformation. The environment of the Gd(III) in the Fc region of whole IgG is not affected by the presence of octasaccharide derived by hydrolysis of type-III pneumococcal polysaccharide, but the corresponding 28-unit saccharide does cause detectable changes. The addition of 16-unit saccharide to anti-(SIII polysaccharide) IgG in the presence of Gd(III) does not change the solvent water proton relaxation rate, although aggregation does occur. The effects of the 28-unit saccharide may be explained therefore by a change in the tumbling time of the IgG. From a study of the effect of various antigen/antibody ratios, it is concluded that the 28-unit-saccharide-induced changes in the Gd(III) environment in the Fc region are caused by the specific geometrical structure of the antigen-antibody complexes formed, and not simply by occupancy of the combining sites on the antibody."}
{"id": "PMID:15543", "title": "Guanosine cyclic monophosphate-dependent protein kinase from foetal calf heart. Purification, general properties and catalytic subunit.", "content": "Cyclic GMP-dependent protein kinase was purified from foetal calf hearts, and its general properties and subunit structure were studied. The enzyme was purified over 900-fold from the heart extract by pH 5.3-isoelectric precipitation, DEAE-cellulose chromatography, Sephadex G-200 filtration and hydroxyapatite treatment. The purified myocardial enzyme, free from cyclic AMP-dependent protein kinase contamination, exhibited an absolute requirement of stimulatory modulator (or crude modulator containing the stimulatory modulator component) for its cyclic GMP-stimulated activity. Inhibitory modulator (protein inhibitor) of cyclic AMP-dependent protein kinase could not stimulate nor inhibit the cyclic GMP target enzyme. The enzyme had Ka values of 0.013, 0.033 and 3.0 micronM for 8-bromo cyclic GMP, cyclic GMP and cyclic AMP respectively. The cyclic GMP-dependent enzyme required Mg2+ and Co2+ for its activity, with optimal concentrations of about 30 and 0.5 mM respectively. The pH optimum for the enzyme activity ranged from 6 to 9. Histones were generally effective substrate proteins. The enzyme exhibited a greater affinity for histones than did the cyclic AMP-dependent class of protein kinase. The holoenzyme (apparent mol.wt. 150 000) of the myocardial cyclic GMP-dependent protein kinase was dissociated into a cyclic GMP-independent catalytic subunit (apparent mol.wt. 60 000) by cyclic GMP and histone. The catalytic subunit required the stimulatory modulator for its activity, as in the case of the holoenzyme in the presence of cyclic GMP.", "contents": "Guanosine cyclic monophosphate-dependent protein kinase from foetal calf heart. Purification, general properties and catalytic subunit. Cyclic GMP-dependent protein kinase was purified from foetal calf hearts, and its general properties and subunit structure were studied. The enzyme was purified over 900-fold from the heart extract by pH 5.3-isoelectric precipitation, DEAE-cellulose chromatography, Sephadex G-200 filtration and hydroxyapatite treatment. The purified myocardial enzyme, free from cyclic AMP-dependent protein kinase contamination, exhibited an absolute requirement of stimulatory modulator (or crude modulator containing the stimulatory modulator component) for its cyclic GMP-stimulated activity. Inhibitory modulator (protein inhibitor) of cyclic AMP-dependent protein kinase could not stimulate nor inhibit the cyclic GMP target enzyme. The enzyme had Ka values of 0.013, 0.033 and 3.0 micronM for 8-bromo cyclic GMP, cyclic GMP and cyclic AMP respectively. The cyclic GMP-dependent enzyme required Mg2+ and Co2+ for its activity, with optimal concentrations of about 30 and 0.5 mM respectively. The pH optimum for the enzyme activity ranged from 6 to 9. Histones were generally effective substrate proteins. The enzyme exhibited a greater affinity for histones than did the cyclic AMP-dependent class of protein kinase. The holoenzyme (apparent mol.wt. 150 000) of the myocardial cyclic GMP-dependent protein kinase was dissociated into a cyclic GMP-independent catalytic subunit (apparent mol.wt. 60 000) by cyclic GMP and histone. The catalytic subunit required the stimulatory modulator for its activity, as in the case of the holoenzyme in the presence of cyclic GMP."}
{"id": "PMID:15544", "title": "Purification and properties of the methane mono-oxygenase enzyme system from Methylosinus trichosporium OB3b.", "content": "1. A three-component enzyme system that catalyses the oxidation of methane to methanol has been highly purified from Methylosinus trichosporium. 2. The components are (i) a soluble CO-binding cytochrome c, (ii) a copper-containing protein and (iii) a small protein; the mol. wts. are 13 000, 47 000 and 9400 respectively. The cytochrome component cannot be replaced by similar cytochrome purified from Pseudomonas extorquens or by horse heart cytochrome c. 3. The stoicheiometry suggests a mono-oxygenase mechanism and the specific activity with methane as substrate is 6 micronmol/min per mg of protein. 4. Other substrates rapidly oxidized are ethane, n-propane, n-butane and CO. Dimethyl ether is not a substrate. 5. The purified enzyme system utilizes ascorbate or, in the presence of partially purified M. trichosporium methanol dehydrogenase, methanol as electron donor but not NADH or NADPH. 6. Activity is highly sensitive to low concentrations of a variety of chelating agents, cyanide, 2-mercaptoethanol and dithiothreitol. 7. Activity is highly pH-dependent (optimum 6.9-7.0) and no component of the enzyme is stable to freezing. 8. The soluble CO-binding cytochrome c shows oxidase acitivity and the relationship between this and the oxygenase activity is discussed.", "contents": "Purification and properties of the methane mono-oxygenase enzyme system from Methylosinus trichosporium OB3b. 1. A three-component enzyme system that catalyses the oxidation of methane to methanol has been highly purified from Methylosinus trichosporium. 2. The components are (i) a soluble CO-binding cytochrome c, (ii) a copper-containing protein and (iii) a small protein; the mol. wts. are 13 000, 47 000 and 9400 respectively. The cytochrome component cannot be replaced by similar cytochrome purified from Pseudomonas extorquens or by horse heart cytochrome c. 3. The stoicheiometry suggests a mono-oxygenase mechanism and the specific activity with methane as substrate is 6 micronmol/min per mg of protein. 4. Other substrates rapidly oxidized are ethane, n-propane, n-butane and CO. Dimethyl ether is not a substrate. 5. The purified enzyme system utilizes ascorbate or, in the presence of partially purified M. trichosporium methanol dehydrogenase, methanol as electron donor but not NADH or NADPH. 6. Activity is highly sensitive to low concentrations of a variety of chelating agents, cyanide, 2-mercaptoethanol and dithiothreitol. 7. Activity is highly pH-dependent (optimum 6.9-7.0) and no component of the enzyme is stable to freezing. 8. The soluble CO-binding cytochrome c shows oxidase acitivity and the relationship between this and the oxygenase activity is discussed."}
{"id": "PMID:15545", "title": "Solubilization, partial purification and properties of N-methylglutamate dehydrogenase from Pseudomonas aminovorans.", "content": "1. Extracts of amine-grown Pseudomonas aminovorans contained a particle-bound N-methylglutamate dehydrogenase (EC 1.5.99.5). The enzyme was not present in succinate-grown cells, and activity appeared before growth began in succinate-grown cells which had been transferred to methylamine growth medium. 2. Membrane-containing preparations from methylamine-grown cells catalysed an N-methylglutamate-dependent uptake of O2 or reduction of cytochrome c, which was sensitive to inhibitors of the electron-transport chain. 3. N-Methylglutamate dehydrogenase activity with phenazine methosulphate or 2,6-dichlorophenol-indophenol as electron acceptor could be solubilized with 1% (w/v) Triton X-100. The solubilized enzyme was much less active with cytochrome c as electron acceptor and did not sediment in 1 h at 150000g. Solubilization was accompanied by a change in the pH optimum for activity. 4. The solubilized enzyme was partially purified by Sepharose 4B and hydroxyapatite chromatograpy to yield a preparation 22-fold increased in specific activity over the crude extract. 5. The partially-purified enzyme was active with sarcosine, N-methylalanine and N-methylaspartate as well as with N-methylglutamate. Evidence suggesting activity with N-methyl D-amino acids as well as with the L-forms was obtained. 6. The enzyme was inhibited by p-chloromercuribenzoate, iodoacetamide and by both ionic and non-ionic detergents. 2-Oxoglutarate and formaldehyde were also inhibitors. 7. Kinetic analysis confirmed previous workers' observations of a group transfer (Ping Pong) mechanism. 8. Spectral observations suggested that the partially purified preparation contained flavoprotein and a b-type cytochrome. 9. The role of the enzyme in the oxidation of methylamine is discussed.", "contents": "Solubilization, partial purification and properties of N-methylglutamate dehydrogenase from Pseudomonas aminovorans. 1. Extracts of amine-grown Pseudomonas aminovorans contained a particle-bound N-methylglutamate dehydrogenase (EC 1.5.99.5). The enzyme was not present in succinate-grown cells, and activity appeared before growth began in succinate-grown cells which had been transferred to methylamine growth medium. 2. Membrane-containing preparations from methylamine-grown cells catalysed an N-methylglutamate-dependent uptake of O2 or reduction of cytochrome c, which was sensitive to inhibitors of the electron-transport chain. 3. N-Methylglutamate dehydrogenase activity with phenazine methosulphate or 2,6-dichlorophenol-indophenol as electron acceptor could be solubilized with 1% (w/v) Triton X-100. The solubilized enzyme was much less active with cytochrome c as electron acceptor and did not sediment in 1 h at 150000g. Solubilization was accompanied by a change in the pH optimum for activity. 4. The solubilized enzyme was partially purified by Sepharose 4B and hydroxyapatite chromatograpy to yield a preparation 22-fold increased in specific activity over the crude extract. 5. The partially-purified enzyme was active with sarcosine, N-methylalanine and N-methylaspartate as well as with N-methylglutamate. Evidence suggesting activity with N-methyl D-amino acids as well as with the L-forms was obtained. 6. The enzyme was inhibited by p-chloromercuribenzoate, iodoacetamide and by both ionic and non-ionic detergents. 2-Oxoglutarate and formaldehyde were also inhibitors. 7. Kinetic analysis confirmed previous workers' observations of a group transfer (Ping Pong) mechanism. 8. Spectral observations suggested that the partially purified preparation contained flavoprotein and a b-type cytochrome. 9. The role of the enzyme in the oxidation of methylamine is discussed."}
{"id": "PMID:15546", "title": "Isolation and characterization of sheep pepsin.", "content": "Sheep pepsin was isolated (approx. 120-fold purification) from aqueous abomasal homogenates by (1) pH fractionation, (2) chromatography on Sepharose 4B-poly-L-lysine columns and (3) gel filtration on Sephadex G-100. The enzyme had mol.wt. approx. 34000, N-terminal valine and C-terminal alanine. The amino acid composition of sheep pepsin was generally similar to that of pig and ox pepsins, with a very low content of basic residues and a high content of acidic and hydroxy-amino acids. The pH optimum for NN-dimethyl-casein and NN-dimethyl-haemoglobin as substrates was approx. 1.8. The Km and kcat. for NN-dimethyl-haemoglobin were 46micronM and 1100min-1 respectively, and for NN-dimethyl-casein the corresponding parameters were 50micronM and 420min-1. These values were generally similar to those for pig and ox pepsins. At the pH optimum of 4.6, the sheep pepsin was about 50% as active on benzyloxycarbonyl-L-histidyl-L-phenyl-alanyl-L-tryptophan ethyl ester as was pig pepsin. The pH optimum for the hydrolysis of N-acetyl-L-phenylalanyl-L-di-iodotyrosine by sheep, ox and pig pepsins was approx. 1.85.", "contents": "Isolation and characterization of sheep pepsin. Sheep pepsin was isolated (approx. 120-fold purification) from aqueous abomasal homogenates by (1) pH fractionation, (2) chromatography on Sepharose 4B-poly-L-lysine columns and (3) gel filtration on Sephadex G-100. The enzyme had mol.wt. approx. 34000, N-terminal valine and C-terminal alanine. The amino acid composition of sheep pepsin was generally similar to that of pig and ox pepsins, with a very low content of basic residues and a high content of acidic and hydroxy-amino acids. The pH optimum for NN-dimethyl-casein and NN-dimethyl-haemoglobin as substrates was approx. 1.8. The Km and kcat. for NN-dimethyl-haemoglobin were 46micronM and 1100min-1 respectively, and for NN-dimethyl-casein the corresponding parameters were 50micronM and 420min-1. These values were generally similar to those for pig and ox pepsins. At the pH optimum of 4.6, the sheep pepsin was about 50% as active on benzyloxycarbonyl-L-histidyl-L-phenyl-alanyl-L-tryptophan ethyl ester as was pig pepsin. The pH optimum for the hydrolysis of N-acetyl-L-phenylalanyl-L-di-iodotyrosine by sheep, ox and pig pepsins was approx. 1.85."}
{"id": "PMID:15547", "title": "Properties of rat liver microsomal stearoyl-coenzyme A desaturase.", "content": "1. Rat liver microsomal stearoyl-CoA desaturase activity was shown to be stimulated by both bovine serum albumin and a basic cytoplasmic protein from rat liver. 2. Partially purified desaturase is unaffected by either of these two proteins. 3. Bovine serum albumin appears to exert its effect on the crude system by protecting the desaturase substrate, stearoly-CoA, from the action of endogenous thiolesterases. 4. By using partially purified enzyme preparations, it was possible to establish the substate specificity of the delta9-fatty acyl-CoA desaturase with the C14, C15, C16, C17, C18 and C19 fatty acyl-CoA substrates. Maximum enzyme activity was shown with stearoyl-CoA decreasing with both palmitoyl-CoA and nonadecanoyl-CoA, as reported previously for free fatty acids. 5. Both cytochrome b5 and NADH-cytochrome b5 reductase (EC 1.6.2.2) are required for these studies and a method is described for the purification of homogeneous preparations of detergent-isolated cytochrome b5 from rat liver. 6. From amino acid analyses, a comparison was made of the hydrophobicity of the membrane portion of cytochrome b5 with the hydrophobicity reported for stearoyl-CoA desaturase. The close resemblance of the two values suggested that unlike cytochrome b5 and its reductase, the stearoyl-CoA desaturase may be largely buried in the endoplasmic reticulum.", "contents": "Properties of rat liver microsomal stearoyl-coenzyme A desaturase. 1. Rat liver microsomal stearoyl-CoA desaturase activity was shown to be stimulated by both bovine serum albumin and a basic cytoplasmic protein from rat liver. 2. Partially purified desaturase is unaffected by either of these two proteins. 3. Bovine serum albumin appears to exert its effect on the crude system by protecting the desaturase substrate, stearoly-CoA, from the action of endogenous thiolesterases. 4. By using partially purified enzyme preparations, it was possible to establish the substate specificity of the delta9-fatty acyl-CoA desaturase with the C14, C15, C16, C17, C18 and C19 fatty acyl-CoA substrates. Maximum enzyme activity was shown with stearoyl-CoA decreasing with both palmitoyl-CoA and nonadecanoyl-CoA, as reported previously for free fatty acids. 5. Both cytochrome b5 and NADH-cytochrome b5 reductase (EC 1.6.2.2) are required for these studies and a method is described for the purification of homogeneous preparations of detergent-isolated cytochrome b5 from rat liver. 6. From amino acid analyses, a comparison was made of the hydrophobicity of the membrane portion of cytochrome b5 with the hydrophobicity reported for stearoyl-CoA desaturase. The close resemblance of the two values suggested that unlike cytochrome b5 and its reductase, the stearoyl-CoA desaturase may be largely buried in the endoplasmic reticulum."}
{"id": "PMID:15548", "title": "The isolation and partial characterization of the major glycoprotein (LGP-I) from the articular lubricating fraction from bovine synovial fluid.", "content": "The articular lubricating fraction from bovine synovial fluid was prepared by repeated fractionation in three consecutive CsCl density gradients to remove completely traces of hyaluronic acid. The major glycoprotein consituent (LGP-I) was then isolated by repeated gel-permeation chromatography. The yield of the LGP-I component was about 20 mg/litre of synovial fluid. Sedimentation-equilibrium measurements showed that this glycoprotein was homogeneous and the mol.wt. was calculated to be 227500. Amino acids represented 43% (w/w) and carbohydrate constituents 44% (w/w) of the molecule. Threonine, glutamic acid, proline and lysine (224, 127, 242 and 128 residues/1000 residues respectively) were the major amino acids. Galactosamine, galactose and N-acetylneuraminic acid (202, 162 and 114 residues/molecule of LGP-I component respectively) accounted for 98% of the total carbohydrate residues present. Small amounts of mannose and glucosamine (1 and 9mol respectively/mol of LGP-I component) were also present. After treatment of LGP-I component with alkali and NaB3H4 radioactivity was incorporated into alpha-aminobutyric acid and alanine in a molar ratio of 4:1, and radioactive galactosaminitol was isolated by ion-exchange chromatography from a cleaved oligosaccharide fraction. These data demonstrate the presence of threonine and serine -O-GalNAc linkages, but only 25% of the theoretical likages involving threonine were cleaved by a beta-elimination reaction. Digestion of LGP-I component with Pronase followed by chromatography on DEAE-cellulose yielded glycopeptide fractions with a similar amino acid and carbohydrate composition to the intact molecule. Treatment of desialylated and intact LGP-I component with galactose oxidase followed by reduction with NaB3H4 revealed the presence of 52mol of terminal galactose in the intact molecule and 153mol of galactose/mol of LGP-I component after treatment with neuraminidase. The data indicate the LGP-I component is composed of a single polypeptide chain containg more than 150 oligaosaccharide side chains composed of O-GaINAc-Gal distributed over the length of the peptide chain and that terminal sialic acid residues are linked to galactose in two-thirds of these side chains.", "contents": "The isolation and partial characterization of the major glycoprotein (LGP-I) from the articular lubricating fraction from bovine synovial fluid. The articular lubricating fraction from bovine synovial fluid was prepared by repeated fractionation in three consecutive CsCl density gradients to remove completely traces of hyaluronic acid. The major glycoprotein consituent (LGP-I) was then isolated by repeated gel-permeation chromatography. The yield of the LGP-I component was about 20 mg/litre of synovial fluid. Sedimentation-equilibrium measurements showed that this glycoprotein was homogeneous and the mol.wt. was calculated to be 227500. Amino acids represented 43% (w/w) and carbohydrate constituents 44% (w/w) of the molecule. Threonine, glutamic acid, proline and lysine (224, 127, 242 and 128 residues/1000 residues respectively) were the major amino acids. Galactosamine, galactose and N-acetylneuraminic acid (202, 162 and 114 residues/molecule of LGP-I component respectively) accounted for 98% of the total carbohydrate residues present. Small amounts of mannose and glucosamine (1 and 9mol respectively/mol of LGP-I component) were also present. After treatment of LGP-I component with alkali and NaB3H4 radioactivity was incorporated into alpha-aminobutyric acid and alanine in a molar ratio of 4:1, and radioactive galactosaminitol was isolated by ion-exchange chromatography from a cleaved oligosaccharide fraction. These data demonstrate the presence of threonine and serine -O-GalNAc linkages, but only 25% of the theoretical likages involving threonine were cleaved by a beta-elimination reaction. Digestion of LGP-I component with Pronase followed by chromatography on DEAE-cellulose yielded glycopeptide fractions with a similar amino acid and carbohydrate composition to the intact molecule. Treatment of desialylated and intact LGP-I component with galactose oxidase followed by reduction with NaB3H4 revealed the presence of 52mol of terminal galactose in the intact molecule and 153mol of galactose/mol of LGP-I component after treatment with neuraminidase. The data indicate the LGP-I component is composed of a single polypeptide chain containg more than 150 oligaosaccharide side chains composed of O-GaINAc-Gal distributed over the length of the peptide chain and that terminal sialic acid residues are linked to galactose in two-thirds of these side chains."}
{"id": "PMID:15549", "title": "Purification and properties of an alpha-D-galactoside galactohydrolase from the seeds of Trifolium repens (white clover).", "content": "Five alpha-D-galactosidases (alpha-D-galactoside galactohydrolase; EC 3.2.1.22) have been identified by chromatography and polyacrylamide-disc-gel electrophoresis in the germinated seeds of Trifolium repens (white clover). alpha-Galactosidase I has been purified to homogeneity with an approx. 2000-fold increase in specific activity. The enzyme was purified by a procedure which included precipitation by dialysis against citrate/phosphate buffer, pH3.5; (NH4)2SO4 precipitation; hydroxyapatite, DEAE-cellulose and ECTEOLA-cellulose column chromatography. Each stage of purification was controlled by polyacrylamide-disc-gel electrophoresis; the purified enzyme showed a single protein band that corresponded to the alpha-D-galactosidic activity. The pH optimum was found to be between pH 3.8 and 4.2; the enzyme is highly thermolabile. Hydrolysis of oligosaccharides and galactomannans has been examined, and it has been found that alpha-galactosidase I exhibits two enzymic activities, namely alpha-D-galactoside galactohydrolase and galactosyltransferase. By the polyacrylamide-gel-electrophoresis method of Hendrick & Smith (1968), and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the mol.wt. has been estimated to be 43 000 and 41 000 respectively. These results indicate that alpha-galactosidase I is a monomeric protein and that both enzymic activities associated with the enzyme reside on the same polypeptide chain.", "contents": "Purification and properties of an alpha-D-galactoside galactohydrolase from the seeds of Trifolium repens (white clover). Five alpha-D-galactosidases (alpha-D-galactoside galactohydrolase; EC 3.2.1.22) have been identified by chromatography and polyacrylamide-disc-gel electrophoresis in the germinated seeds of Trifolium repens (white clover). alpha-Galactosidase I has been purified to homogeneity with an approx. 2000-fold increase in specific activity. The enzyme was purified by a procedure which included precipitation by dialysis against citrate/phosphate buffer, pH3.5; (NH4)2SO4 precipitation; hydroxyapatite, DEAE-cellulose and ECTEOLA-cellulose column chromatography. Each stage of purification was controlled by polyacrylamide-disc-gel electrophoresis; the purified enzyme showed a single protein band that corresponded to the alpha-D-galactosidic activity. The pH optimum was found to be between pH 3.8 and 4.2; the enzyme is highly thermolabile. Hydrolysis of oligosaccharides and galactomannans has been examined, and it has been found that alpha-galactosidase I exhibits two enzymic activities, namely alpha-D-galactoside galactohydrolase and galactosyltransferase. By the polyacrylamide-gel-electrophoresis method of Hendrick & Smith (1968), and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the mol.wt. has been estimated to be 43 000 and 41 000 respectively. These results indicate that alpha-galactosidase I is a monomeric protein and that both enzymic activities associated with the enzyme reside on the same polypeptide chain."}
{"id": "PMID:15550", "title": "An examination of potential matrices for the affinity chromatography of NADP+-linked dehydrogenases with special reference to 6-phosphogluconate dehydrogenase.", "content": "1. 6-phosphogluconate dehydrogenase from sheep liver has been purified 350-fold by affinity chromatography with a final specific activity of 18 micronmol of NADP+/reduced min per mg of protein and an overall yield of greater than 40%. 2. A systematic investigation of potential ligands has been carried out: these included 6-phosphogluconate and NADP+, pyridoxal phosphate and several immobilized nucleotides. The results indicate that NADP+ is the most suitable ligand for the purification of 6-phosphogluconate dehydrogenase. 3. The effects of pH and alternative eluents have been examined in relation to the parameters known to affect the desorption phase of affinity chromatography; careful manipulation of the elution conditions permitted the separation of glucose 6-phosphate dehydrogenase, glutathione reductase and 6-phosphogluconate dehydrogenase from sheep liver on NADP+-Sepharose 4B. 4. A large-scale purification scheme for 6-phosphogluconate dehydrogenase is presented that uses the competitive inhibitors inorganic pyrophosphate and citrate as specific eluents.", "contents": "An examination of potential matrices for the affinity chromatography of NADP+-linked dehydrogenases with special reference to 6-phosphogluconate dehydrogenase. 1. 6-phosphogluconate dehydrogenase from sheep liver has been purified 350-fold by affinity chromatography with a final specific activity of 18 micronmol of NADP+/reduced min per mg of protein and an overall yield of greater than 40%. 2. A systematic investigation of potential ligands has been carried out: these included 6-phosphogluconate and NADP+, pyridoxal phosphate and several immobilized nucleotides. The results indicate that NADP+ is the most suitable ligand for the purification of 6-phosphogluconate dehydrogenase. 3. The effects of pH and alternative eluents have been examined in relation to the parameters known to affect the desorption phase of affinity chromatography; careful manipulation of the elution conditions permitted the separation of glucose 6-phosphate dehydrogenase, glutathione reductase and 6-phosphogluconate dehydrogenase from sheep liver on NADP+-Sepharose 4B. 4. A large-scale purification scheme for 6-phosphogluconate dehydrogenase is presented that uses the competitive inhibitors inorganic pyrophosphate and citrate as specific eluents."}
{"id": "PMID:15551", "title": "Large fragments of human serum albumin.", "content": "Large fragments of human serum albumin were produced by treatment of the native protein with pepsin at pH3.5. Published sequences of human albumin [Behrens, Spiekerman & Brown (1975) Fed. Proc. Fed. Am. Soc. Exp. Biol. 34, 591; Meloun, Moravek & Kostka (1975) FEBSLett.58, 134-137]were used to locate the fragments in the primary structure. The fragments support both the sequence and proposed disulphide-linkage pattern (Behrens et al., 1975). As the pH of a solution of albumin is lowered from pH4 to pH3.5, the protein undergoes a reversible conformational change known as the N-F transition. The distribution of large fragments of human albumin digested with pepsin in the above pH region was critically dependent on pH. It appeared that this distribution was dependent on the conformation of the protein at low pH, rather than the activity of pepsin. The yields of the large fragments produced by peptic digestion at different values of pH suggested that the C-terminal region of albumin unfolds or separates from the rest of the molecule during the N-F transition. The similarity of peptic fragments of human and bovine albumin produced under identical conditions supports the proposed similar tertiary structure of these molecules.", "contents": "Large fragments of human serum albumin. Large fragments of human serum albumin were produced by treatment of the native protein with pepsin at pH3.5. Published sequences of human albumin [Behrens, Spiekerman & Brown (1975) Fed. Proc. Fed. Am. Soc. Exp. Biol. 34, 591; Meloun, Moravek & Kostka (1975) FEBSLett.58, 134-137]were used to locate the fragments in the primary structure. The fragments support both the sequence and proposed disulphide-linkage pattern (Behrens et al., 1975). As the pH of a solution of albumin is lowered from pH4 to pH3.5, the protein undergoes a reversible conformational change known as the N-F transition. The distribution of large fragments of human albumin digested with pepsin in the above pH region was critically dependent on pH. It appeared that this distribution was dependent on the conformation of the protein at low pH, rather than the activity of pepsin. The yields of the large fragments produced by peptic digestion at different values of pH suggested that the C-terminal region of albumin unfolds or separates from the rest of the molecule during the N-F transition. The similarity of peptic fragments of human and bovine albumin produced under identical conditions supports the proposed similar tertiary structure of these molecules."}
{"id": "PMID:15552", "title": "Modification of pig heart lactate dehydrogenase with methyl methanethiosulphonate to produce an enzyme with altered catalytic activity.", "content": "Methyl methanethiosulphonate was used to produce a modification of the essential thiol group in lactate dehydrogenase which leaves the enzyme catalytically active. Methyl methanethiosulphonate produced a progressive inhibition of enzyme activity, with 2mM-pyruvate and 0.14mM-NADH as substrates, which ceased once the enzyme had lost 70-90% of its activity. In contrast, with 10mM-lactate and 0.4mM-NAD+ as substrates the enzyme was virtually completely inhibited. The observed inhibition was critically dependent on the chosen substrate concentration, since methanethiolation with methyl methanethiosulphonate resulted in a large decrease in affinity for pyruvate. At 0.14mM-NADH, methanethiolation increased the apparent KmPyr from from 40micronM for the control enzyme to 12mM for the modified enzyme. Steady-state kinetics showed that there was not a statistically significant change in either KmNADH or KsNADH. At saturating NADH and pyruvate concentrations, the Vmax. was virtually unaffected for the methanethiolated enzyme. However, a decrease in Vmax. was observed when the modified enzyme was incubated in dilute solution. The modification of lactate dehydrogenase by methyl methanethiosulphonate involved the active site, since inhibition was completely prevented by substrate-analogue pairs such as NADH and oxamate or NAD+ and oxalate. The formation of complexes between methanethiolated lactate dehydrogenase and substrates or substrate analogues can also be shown by re-activation experiments. The methanethiolated enzyme was re-activated in a time-dependent reaction by dithiothreitol and this was prevented by oxamate, by NADH and by NADH plus oxamate in increasing order of effectiveness. The results of this work are interpreted in terms of a role for the essential thiol group in the binding of substrates.", "contents": "Modification of pig heart lactate dehydrogenase with methyl methanethiosulphonate to produce an enzyme with altered catalytic activity. Methyl methanethiosulphonate was used to produce a modification of the essential thiol group in lactate dehydrogenase which leaves the enzyme catalytically active. Methyl methanethiosulphonate produced a progressive inhibition of enzyme activity, with 2mM-pyruvate and 0.14mM-NADH as substrates, which ceased once the enzyme had lost 70-90% of its activity. In contrast, with 10mM-lactate and 0.4mM-NAD+ as substrates the enzyme was virtually completely inhibited. The observed inhibition was critically dependent on the chosen substrate concentration, since methanethiolation with methyl methanethiosulphonate resulted in a large decrease in affinity for pyruvate. At 0.14mM-NADH, methanethiolation increased the apparent KmPyr from from 40micronM for the control enzyme to 12mM for the modified enzyme. Steady-state kinetics showed that there was not a statistically significant change in either KmNADH or KsNADH. At saturating NADH and pyruvate concentrations, the Vmax. was virtually unaffected for the methanethiolated enzyme. However, a decrease in Vmax. was observed when the modified enzyme was incubated in dilute solution. The modification of lactate dehydrogenase by methyl methanethiosulphonate involved the active site, since inhibition was completely prevented by substrate-analogue pairs such as NADH and oxamate or NAD+ and oxalate. The formation of complexes between methanethiolated lactate dehydrogenase and substrates or substrate analogues can also be shown by re-activation experiments. The methanethiolated enzyme was re-activated in a time-dependent reaction by dithiothreitol and this was prevented by oxamate, by NADH and by NADH plus oxamate in increasing order of effectiveness. The results of this work are interpreted in terms of a role for the essential thiol group in the binding of substrates."}
{"id": "PMID:15553", "title": "Studies on the soluble and membrane-bound amino acid 2-naphthylamidases in pig and human epidermis.", "content": "1. Membrane-bound (particulate) and soluble amino acid 2-naphthylamidases (EC 3.5.1.-) were present in subcellular fractions of epidermis from pig and human. 2. The particulate enzymes exhibited Michaelis-Menten kinetics, with Km 5.1x10(-5) (pig) and Km 7.3x10(-5)M (human) for the substrate L-leucine 2-naphthylamide. They were inhibited by puromycin and partially inhibited by EDTA. They did not require heavy metals and were not inhibited by thiol-group-blocking agents. Their pH optima were 7.0 (human) and 6.6 (pig). The particulate enzyme from pig epidermis retained 50% activity after 30 min at 70 degrees C. 3. The soluble amino acid 2-naphthylamidases gave sigmoidal curves for reaction velocity versus substrate concentration, and the kinetic data suggested that there was positive co-operativity between binding sites. This co-operativity was lost after treatment with 0.1mM-p-hydroxymercuribenzoate and the enzymes showed first-order kinetics at low substrate concentrations. The soluble enzymes were inhibited by puromycin and by thiol-group-blocking agents and activated by dithiothreitol. They were inactivated above 60 degrees C and lost activity on storage, but this could be restored with dithiothreitol. 4. The amino acid 2-naphthylamidases of human epidermis were much more active (2.5 times) towards L-alanine 2-naphthylamide than towards the commonly used substrate L-leucine 2-naphthylamide. 5. The kinetics of both the solube and particulate enzymes from epidermis of some elderly patients with either diabetes or ischaemia showed some differences from the kinetics of enzymes from healthy epidermis from younger individuals.", "contents": "Studies on the soluble and membrane-bound amino acid 2-naphthylamidases in pig and human epidermis. 1. Membrane-bound (particulate) and soluble amino acid 2-naphthylamidases (EC 3.5.1.-) were present in subcellular fractions of epidermis from pig and human. 2. The particulate enzymes exhibited Michaelis-Menten kinetics, with Km 5.1x10(-5) (pig) and Km 7.3x10(-5)M (human) for the substrate L-leucine 2-naphthylamide. They were inhibited by puromycin and partially inhibited by EDTA. They did not require heavy metals and were not inhibited by thiol-group-blocking agents. Their pH optima were 7.0 (human) and 6.6 (pig). The particulate enzyme from pig epidermis retained 50% activity after 30 min at 70 degrees C. 3. The soluble amino acid 2-naphthylamidases gave sigmoidal curves for reaction velocity versus substrate concentration, and the kinetic data suggested that there was positive co-operativity between binding sites. This co-operativity was lost after treatment with 0.1mM-p-hydroxymercuribenzoate and the enzymes showed first-order kinetics at low substrate concentrations. The soluble enzymes were inhibited by puromycin and by thiol-group-blocking agents and activated by dithiothreitol. They were inactivated above 60 degrees C and lost activity on storage, but this could be restored with dithiothreitol. 4. The amino acid 2-naphthylamidases of human epidermis were much more active (2.5 times) towards L-alanine 2-naphthylamide than towards the commonly used substrate L-leucine 2-naphthylamide. 5. The kinetics of both the solube and particulate enzymes from epidermis of some elderly patients with either diabetes or ischaemia showed some differences from the kinetics of enzymes from healthy epidermis from younger individuals."}
{"id": "PMID:15554", "title": "Self-association of alpha-chymotrypsin at low ionic strength in the vicinity of its pH optimum.", "content": "The self-association of alpha-chymotrypsin and its di-isopropyl phosphoryl derivative in in I0.03 sodium phophate buffer, pH7,9, was investigated by velocity sedimentation, equilibrium sedimentation and difference gel chromatography. No differences between the native and chemically modified enzyme were observed in the ultracentrifuge studies, and only a marginal (0.6%) difference in weight-average elution volume was detected by difference gel chromatography of 5g/litre solutions on Sephadex G-75. From quantitative analyses of sedimentation velocity and sedimentation-equilibrium distributions obtained with iPr2P (di-isopropylphosphoryl)-chymotrypsin, the polymerizing system is postulated to involve an indefinite association of dimer (with an isodesmic association constant of 0.68 litre/g) that is formed by a discrete dimerization step with equilibrium constant 0.25 litre/g. In addition to providing the best fit of the experimental results, this model of chymotrypsin polymerization at low ionic strength is also consistent with an earlier observation that dimer formation is a symmetrical head-to-head phenomenon under conditions of higher ionic strength (I0.29, pH7.9) where association is restricted to a monomer-dimer equilibrium. It is proposed that the dimerization process is essentially unchanged by variation in ionic strength at pH7.9, and that higher polymers are formed by an entirely different mechanism involving largely electrostatic interactions between dimeric species.", "contents": "Self-association of alpha-chymotrypsin at low ionic strength in the vicinity of its pH optimum. The self-association of alpha-chymotrypsin and its di-isopropyl phosphoryl derivative in in I0.03 sodium phophate buffer, pH7,9, was investigated by velocity sedimentation, equilibrium sedimentation and difference gel chromatography. No differences between the native and chemically modified enzyme were observed in the ultracentrifuge studies, and only a marginal (0.6%) difference in weight-average elution volume was detected by difference gel chromatography of 5g/litre solutions on Sephadex G-75. From quantitative analyses of sedimentation velocity and sedimentation-equilibrium distributions obtained with iPr2P (di-isopropylphosphoryl)-chymotrypsin, the polymerizing system is postulated to involve an indefinite association of dimer (with an isodesmic association constant of 0.68 litre/g) that is formed by a discrete dimerization step with equilibrium constant 0.25 litre/g. In addition to providing the best fit of the experimental results, this model of chymotrypsin polymerization at low ionic strength is also consistent with an earlier observation that dimer formation is a symmetrical head-to-head phenomenon under conditions of higher ionic strength (I0.29, pH7.9) where association is restricted to a monomer-dimer equilibrium. It is proposed that the dimerization process is essentially unchanged by variation in ionic strength at pH7.9, and that higher polymers are formed by an entirely different mechanism involving largely electrostatic interactions between dimeric species."}
{"id": "PMID:15555", "title": "Proton uptake linked to the 3-deoxy-2-oxo-d-gluconate-transport system of Escherichia coli.", "content": "Genetic and kinetic evidence is presented to show that the carrier-mediated uptake of the anionic sugars 3-deoxy-2-oxo-D-gluconate and D-glucuronate by Escherichia coli involves the concomitant transport of protons.", "contents": "Proton uptake linked to the 3-deoxy-2-oxo-d-gluconate-transport system of Escherichia coli. Genetic and kinetic evidence is presented to show that the carrier-mediated uptake of the anionic sugars 3-deoxy-2-oxo-D-gluconate and D-glucuronate by Escherichia coli involves the concomitant transport of protons."}
{"id": "PMID:15556", "title": "An oligomycin-resistant adenosine triphosphatase and its effects on cellular growth, mitochondrial oxidative phosphorylation and respiratory proton translocation in Saccharomyces cerevisiae.", "content": "Mutations at the OLI 1 or OLI 2 loci of mitochondria DNA in Saccharomyces cerevisiae are associated with a diminished growth rate in nutritionally suboptimal cultures supplemented with an oxidizable carbon source. In the case of mutant OR146(OLI1) there is a 35% loss of mitochondrial protein during fractionation in vitro, suggesting that the mutationally altered adenosine triphosphatase(ATPase) confers some instability on the mitochondrial membrane. The possibility is discussed that this reflects an unstable mitchondrial population in vivo, leading the observed growth deficiency. Mitochondria from mutant OR146 at the OLI 1 locus show a relatively oligomycin-resistant State-3 respiration, but the same ADP/O and respiratory-control quotients as the isonuclear wild-type. A slightly lowered Qo2 with NADH-linked substrates was observed and is discussed. For both strains the apparent H+/O ratios were close to 4 with pyruvate, ethanol and alpha-oxoglutarate, but consistently lower with succinate and citrate. For each substrate a characteristic t 1/2 (time for half-decay of the transmembrane pH differential) range was found, consistent with the view that the substrates effecitvely carry the protons back across the membrane. As expected, H+/O ratios were independent of t 1/2 for all substrates, with the exception of alpha-oxoglutarate in the case of the wild-type, where an inverse correlation was found. The lack of this correlation in the case of the mutant was the only apparent difference in the translocation parameters observed. A hypothesis relating this to the functioning of the oligomycin-resistant ATPase is proposed.", "contents": "An oligomycin-resistant adenosine triphosphatase and its effects on cellular growth, mitochondrial oxidative phosphorylation and respiratory proton translocation in Saccharomyces cerevisiae. Mutations at the OLI 1 or OLI 2 loci of mitochondria DNA in Saccharomyces cerevisiae are associated with a diminished growth rate in nutritionally suboptimal cultures supplemented with an oxidizable carbon source. In the case of mutant OR146(OLI1) there is a 35% loss of mitochondrial protein during fractionation in vitro, suggesting that the mutationally altered adenosine triphosphatase(ATPase) confers some instability on the mitochondrial membrane. The possibility is discussed that this reflects an unstable mitchondrial population in vivo, leading the observed growth deficiency. Mitochondria from mutant OR146 at the OLI 1 locus show a relatively oligomycin-resistant State-3 respiration, but the same ADP/O and respiratory-control quotients as the isonuclear wild-type. A slightly lowered Qo2 with NADH-linked substrates was observed and is discussed. For both strains the apparent H+/O ratios were close to 4 with pyruvate, ethanol and alpha-oxoglutarate, but consistently lower with succinate and citrate. For each substrate a characteristic t 1/2 (time for half-decay of the transmembrane pH differential) range was found, consistent with the view that the substrates effecitvely carry the protons back across the membrane. As expected, H+/O ratios were independent of t 1/2 for all substrates, with the exception of alpha-oxoglutarate in the case of the wild-type, where an inverse correlation was found. The lack of this correlation in the case of the mutant was the only apparent difference in the translocation parameters observed. A hypothesis relating this to the functioning of the oligomycin-resistant ATPase is proposed."}
{"id": "PMID:15557", "title": "The metabolism of benzyl isothiocyanate and its cysteine conjugate.", "content": "1. The corresponding cysteine conjugate was formed when the GSH (reduced glutathione) or cysteinylglycine conjugates of benzyl isothiocyanate were incubated with rat liver or kidney homogenates. When the cysteine conjugate of benzyl isothiocyanate was similarly incubated in the presence of acetyl-CoA, the corresponding N-acetylcysteine conjugate (mercapturic acid) was formed. 2. The non-enzymic reaction of GSH with benzyl isothiocyanate was rapid and was catalysed by rat liver cytosol. 3. The mercapturic acid was excreted in the urine of rats dosed with benzyl isothiocyanate or its GSH, cysteinyl-glycine or cysteine conjugate, and was isolated as the dicyclohexylamine salt. 4. An oral dose of the cysteine conjugate of [14C]benzyl isothiocyanate was rapidly absorbed and excreted by rats and dogs. After 3 days, rats had excreted a mean of 92.4 and 5.6% of the dose in the urine and faeces respectively, and dogs had excreted a mean of 86.3 and 13.2% respectively. 5. After an oral dose of the cystein conjugate of [C]benzyl isothiocyanate, the major 14C-labelled metabolite in rat urine was the corresponding mercapturic acid  (62% of the dose), whereas in dog urine it was hippuric acid (40% of the dose). 5. Mercapturic acid biosynthesis may be an important route of metabolism of certain isothiocyanates in some mammalian species.", "contents": "The metabolism of benzyl isothiocyanate and its cysteine conjugate. 1. The corresponding cysteine conjugate was formed when the GSH (reduced glutathione) or cysteinylglycine conjugates of benzyl isothiocyanate were incubated with rat liver or kidney homogenates. When the cysteine conjugate of benzyl isothiocyanate was similarly incubated in the presence of acetyl-CoA, the corresponding N-acetylcysteine conjugate (mercapturic acid) was formed. 2. The non-enzymic reaction of GSH with benzyl isothiocyanate was rapid and was catalysed by rat liver cytosol. 3. The mercapturic acid was excreted in the urine of rats dosed with benzyl isothiocyanate or its GSH, cysteinyl-glycine or cysteine conjugate, and was isolated as the dicyclohexylamine salt. 4. An oral dose of the cysteine conjugate of [14C]benzyl isothiocyanate was rapidly absorbed and excreted by rats and dogs. After 3 days, rats had excreted a mean of 92.4 and 5.6% of the dose in the urine and faeces respectively, and dogs had excreted a mean of 86.3 and 13.2% respectively. 5. After an oral dose of the cystein conjugate of [C]benzyl isothiocyanate, the major 14C-labelled metabolite in rat urine was the corresponding mercapturic acid  (62% of the dose), whereas in dog urine it was hippuric acid (40% of the dose). 5. Mercapturic acid biosynthesis may be an important route of metabolism of certain isothiocyanates in some mammalian species."}
{"id": "PMID:15558", "title": "Transport of galactose, glucose and their molecular analogues by Escherichia coli K12.", "content": "1. Strains of Escherichia coli K12 were made that are unable to assimilate glucose by the phosphotransferase system, since they lack the glucose-specific components specified by the genes ptsG and ptsM. 2. Derivative organisms lacking the methyl galactoside or galactose-specific transport system were examined for their ability to transport galactose, d-fucose, methyl beta-D-galactoside, glucose, 2-deoxy-D-glucose and methyl alpha-D-glucoside. 3. Galactose, glucose and to a lesser extent fucose are substrates for both transport systems. 4. 2-Deoxyglucose is transported on the galactose-specific but not the methyl galactoside system. 5. The ability of sugars to elicit anaerobic proton transport is associated with the galactose-specific, but not with the methyl galactoside transport activity. Hence a chemiosmotic mechanism of energization is likely to apply to the former but not to the latter. Alternatively the methyl galactoside system may be switched off under certain conditions, which would indicate a novel regulatory mechanism. 6. Details of the procedure for the derivation of strains may be obtained from the authors, and have been deposited as Supplementary Publication SUP 50074 (8 pages at the) British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1977), 161,1.", "contents": "Transport of galactose, glucose and their molecular analogues by Escherichia coli K12. 1. Strains of Escherichia coli K12 were made that are unable to assimilate glucose by the phosphotransferase system, since they lack the glucose-specific components specified by the genes ptsG and ptsM. 2. Derivative organisms lacking the methyl galactoside or galactose-specific transport system were examined for their ability to transport galactose, d-fucose, methyl beta-D-galactoside, glucose, 2-deoxy-D-glucose and methyl alpha-D-glucoside. 3. Galactose, glucose and to a lesser extent fucose are substrates for both transport systems. 4. 2-Deoxyglucose is transported on the galactose-specific but not the methyl galactoside system. 5. The ability of sugars to elicit anaerobic proton transport is associated with the galactose-specific, but not with the methyl galactoside transport activity. Hence a chemiosmotic mechanism of energization is likely to apply to the former but not to the latter. Alternatively the methyl galactoside system may be switched off under certain conditions, which would indicate a novel regulatory mechanism. 6. Details of the procedure for the derivation of strains may be obtained from the authors, and have been deposited as Supplementary Publication SUP 50074 (8 pages at the) British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1977), 161,1."}
{"id": "PMID:15559", "title": "Occurrence of ornithine decarboxylase and polyamines in cartilage.", "content": "The activity of ornithine decarboxylase was investigated in cartilage from chick embryos, rabbits, rats and human foetuses. The enzyme activity in these cartilages was of the same order as the detected in other body tissues. Ornithine decarboxylase activity in chick-embryo cartilage and liver was the same when compared on the basis of total soluble tissue protein. The cartilage enzyme exhibited a pH optimum of 6.5 and a Km for ornithine of 0.16mM. Ornithine decarboxylase activity in chick-embryo pelvic leaflets was maintained at the value in vivo for up to 22h when the isolated tissue was incubated in a modified Waymouth's medium (MB 752/1) at 37 degrees C. After addition of cycloheximide to the incubation medium, ornithine decarboxylase activity declined, with a half-life of 40 min. The concentrations of the polyamines spermidine and spermine in chick-embryo pelvic cartilage and rabbit costal cartilage were of the same order as the concentrations detected in other tissues.", "contents": "Occurrence of ornithine decarboxylase and polyamines in cartilage. The activity of ornithine decarboxylase was investigated in cartilage from chick embryos, rabbits, rats and human foetuses. The enzyme activity in these cartilages was of the same order as the detected in other body tissues. Ornithine decarboxylase activity in chick-embryo cartilage and liver was the same when compared on the basis of total soluble tissue protein. The cartilage enzyme exhibited a pH optimum of 6.5 and a Km for ornithine of 0.16mM. Ornithine decarboxylase activity in chick-embryo pelvic leaflets was maintained at the value in vivo for up to 22h when the isolated tissue was incubated in a modified Waymouth's medium (MB 752/1) at 37 degrees C. After addition of cycloheximide to the incubation medium, ornithine decarboxylase activity declined, with a half-life of 40 min. The concentrations of the polyamines spermidine and spermine in chick-embryo pelvic cartilage and rabbit costal cartilage were of the same order as the concentrations detected in other tissues."}
{"id": "PMID:15560", "title": "Binding of magnesium ions to cell walls of Bacillus subtilis W23 containing teichoic acid or teichuronic acid.", "content": "When grown in a chemostat under various nutritional conditions, cells of Bacillus subtilis W23 produce walls containing teichoic acid or teichuronic acid. The binding of Mg2+ to these walls and to the isolated anionic polymers in solution was measured by equilibrium dialysis. In solution the ribitol teichoic acid bound Mg2+ in the molar ratio Mg2+/P=1:1 with an apparent association constant (Kassoc.) of 0.61 X 10(3)M-1, and the teichuronic acid bound Mg2+ in the ratio Mg2+/CO2-=1.1, Kassoc.=0.3 X 10(3)M-1. Cell walls containing teichuronic acid exhibited closely similar binding properties to those containing teichoic acid; in both cases Mg2+ was bound in the ratio Mg/P or Mg/CO2- of 0.5:1 and with a greater affinity than displayed by the isolated polymers in solution. It was concluded that Mg2+ ions are bound bivalently between anionic centres in the walls and that the incorporation of teichoic acid or teichuronic acid into the walls gives rise to similar ion-binding and charged properties. The results are discussed in relation to the possible functions of anionic polymers in cell walls.", "contents": "Binding of magnesium ions to cell walls of Bacillus subtilis W23 containing teichoic acid or teichuronic acid. When grown in a chemostat under various nutritional conditions, cells of Bacillus subtilis W23 produce walls containing teichoic acid or teichuronic acid. The binding of Mg2+ to these walls and to the isolated anionic polymers in solution was measured by equilibrium dialysis. In solution the ribitol teichoic acid bound Mg2+ in the molar ratio Mg2+/P=1:1 with an apparent association constant (Kassoc.) of 0.61 X 10(3)M-1, and the teichuronic acid bound Mg2+ in the ratio Mg2+/CO2-=1.1, Kassoc.=0.3 X 10(3)M-1. Cell walls containing teichuronic acid exhibited closely similar binding properties to those containing teichoic acid; in both cases Mg2+ was bound in the ratio Mg/P or Mg/CO2- of 0.5:1 and with a greater affinity than displayed by the isolated polymers in solution. It was concluded that Mg2+ ions are bound bivalently between anionic centres in the walls and that the incorporation of teichoic acid or teichuronic acid into the walls gives rise to similar ion-binding and charged properties. The results are discussed in relation to the possible functions of anionic polymers in cell walls."}
{"id": "PMID:15568", "title": "[The effect of the rauwolfia-alkaloids ajmaline, rescinnamine and reserpine on the catecholamine contents of the heart (author's transl)].", "content": "The effect of three rauwolfia-alkaloids and two semi-synthetic derivatives on the catecholamine content of the hearts of guinea pigs was examined. The substances were: ajamaline, N-methyl-ajamaline, N-n-propylajmaline, rescinnamine and reserpine. The presence of catecholamines in isolated atria was tested with tyramine (10(-5) g/ml). Rescinnamine and reserpine depleted the hearts of catecholamines, ajmaline and its derivatives did not.", "contents": "[The effect of the rauwolfia-alkaloids ajmaline, rescinnamine and reserpine on the catecholamine contents of the heart (author's transl)]. The effect of three rauwolfia-alkaloids and two semi-synthetic derivatives on the catecholamine content of the hearts of guinea pigs was examined. The substances were: ajamaline, N-methyl-ajamaline, N-n-propylajmaline, rescinnamine and reserpine. The presence of catecholamines in isolated atria was tested with tyramine (10(-5) g/ml). Rescinnamine and reserpine depleted the hearts of catecholamines, ajmaline and its derivatives did not."}
{"id": "PMID:15569", "title": "[Action of partially cyclic and ring methylated nikethamide analogs. Structure-activity relationships of analeptics of the nicethamide type].", "content": "Investigation concerning the respiratory-analeptical effect of partially cyclic and ring methylated nicethamide analogues are reported. The respiration of the rabbit determined by the mask method, served as pharmacological model.", "contents": "[Action of partially cyclic and ring methylated nikethamide analogs. Structure-activity relationships of analeptics of the nicethamide type]. Investigation concerning the respiratory-analeptical effect of partially cyclic and ring methylated nicethamide analogues are reported. The respiration of the rabbit determined by the mask method, served as pharmacological model."}
{"id": "PMID:15570", "title": "[The effects of barbiturates on the embryonic growth of seedling of lepidium sativum L (author's transl)].", "content": "The influence of some important barbiturates on the capacity to stimulate or to stop the growth of seedling of Lepidium sativum L. was tested and the results statistically evaluated. Phenobarbital, cyclobarbital and pentobarbitial show a significant stimulating effect on growth between 10(-2) and 10(-4) moles/l. All barbiturates in concentrations over 10(-3)M act strongly inhibiting. The average inhibitory concentrations (ID50) show a clear dependence on biological properties, in the first place the partition coefficient.", "contents": "[The effects of barbiturates on the embryonic growth of seedling of lepidium sativum L (author's transl)]. The influence of some important barbiturates on the capacity to stimulate or to stop the growth of seedling of Lepidium sativum L. was tested and the results statistically evaluated. Phenobarbital, cyclobarbital and pentobarbitial show a significant stimulating effect on growth between 10(-2) and 10(-4) moles/l. All barbiturates in concentrations over 10(-3)M act strongly inhibiting. The average inhibitory concentrations (ID50) show a clear dependence on biological properties, in the first place the partition coefficient."}
{"id": "PMID:15571", "title": "High performance liquid chromatography in research of pharmacokinetics and metabolism.", "content": "High performance liquid chromatography in connection with monochromatic UV-detection has proved to be a powerful tool for separation and quantitative determination of drugs and their metabolites in body fluids. Serum samples from volunteers medicated with the psychotropic drugs fosazepam and nomifensine are analysed by this method. Separation times are less than 5 min; the detection limits are within the range of 30-50 ng/ml serum. The reliability of the method is discussed: The results are compared to those from the same serum samples obtained by measurement of total radioactivity and by quantitative mass spectrometry in order to confirm the accuracy of the method. Examples of the pharmacokinetic profile of the two drugs and their metabolites in serum are presented, based on analysis by the methods described.", "contents": "High performance liquid chromatography in research of pharmacokinetics and metabolism. High performance liquid chromatography in connection with monochromatic UV-detection has proved to be a powerful tool for separation and quantitative determination of drugs and their metabolites in body fluids. Serum samples from volunteers medicated with the psychotropic drugs fosazepam and nomifensine are analysed by this method. Separation times are less than 5 min; the detection limits are within the range of 30-50 ng/ml serum. The reliability of the method is discussed: The results are compared to those from the same serum samples obtained by measurement of total radioactivity and by quantitative mass spectrometry in order to confirm the accuracy of the method. Examples of the pharmacokinetic profile of the two drugs and their metabolites in serum are presented, based on analysis by the methods described."}
{"id": "PMID:15572", "title": "[Compound with bronchospasmolytical activity from the chemical class of beta-phenylethyl-aminoalkyl-xanthines (author's transl)].", "content": "1. 7-(3-[2-(3,5-Dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, D 1959, Bronchospasmin) was developed as a bronchospasmolytic agent from the structure class of the phenylethyl-aminoalkyl-xanthines. 2. The pharmacological effects characterize reproterol as a bronchospasmolytic with preferential impact on the adrenergic beta2-receptors. 3. In the therapeutic dose range, reproterol stands out because of its nearly non-existent cardiovascular or central nervous side effects. Effects of over and above pharmacodynamically effective doses as well as toxic ones may be reversed with beta1-receptor blockers.", "contents": "[Compound with bronchospasmolytical activity from the chemical class of beta-phenylethyl-aminoalkyl-xanthines (author's transl)]. 1. 7-(3-[2-(3,5-Dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, D 1959, Bronchospasmin) was developed as a bronchospasmolytic agent from the structure class of the phenylethyl-aminoalkyl-xanthines. 2. The pharmacological effects characterize reproterol as a bronchospasmolytic with preferential impact on the adrenergic beta2-receptors. 3. In the therapeutic dose range, reproterol stands out because of its nearly non-existent cardiovascular or central nervous side effects. Effects of over and above pharmacodynamically effective doses as well as toxic ones may be reversed with beta1-receptor blockers."}
{"id": "PMID:15581", "title": "Purification and characterization of guinea-pig epidermal acid phosphatase.", "content": "Guinea-pig epidermal acid phosphatase has been purified approximately 120-fold by a procedure including acid treatment, CM-cellulose and DEAE-cellulose chromatography, and gel filtration on Sephadex G-100. The enzyme had a pH optimum at 5-0 and the optimal temperature for activity was approximately 50 degrees C. The enzyme was not activated by divalent cations or 2-mercaptoethanol, but it was inhibited by p-chloromercuribenzoate and by fluoride. The km value for p-nitrophenyl phosphate was 1-31x10-4 M, the molecular weight was about 73,000 as determined by Sephadex G-100 gel filtration and the isoelectric point was 6.1. The enzyme hydrolyzed deoxyribonucleoside monophosphates to deoxyribonucleosides.", "contents": "Purification and characterization of guinea-pig epidermal acid phosphatase. Guinea-pig epidermal acid phosphatase has been purified approximately 120-fold by a procedure including acid treatment, CM-cellulose and DEAE-cellulose chromatography, and gel filtration on Sephadex G-100. The enzyme had a pH optimum at 5-0 and the optimal temperature for activity was approximately 50 degrees C. The enzyme was not activated by divalent cations or 2-mercaptoethanol, but it was inhibited by p-chloromercuribenzoate and by fluoride. The km value for p-nitrophenyl phosphate was 1-31x10-4 M, the molecular weight was about 73,000 as determined by Sephadex G-100 gel filtration and the isoelectric point was 6.1. The enzyme hydrolyzed deoxyribonucleoside monophosphates to deoxyribonucleosides."}
{"id": "PMID:15582", "title": "Neutrophil function in bone marrow transplant recipients.", "content": "The neutrophil function of seven patients receiving allogeneic bone marrow transplantion was studied. Five of the patients had been transplanted for aplastic anaemia and two for acute leukaemia. Determinations were made of neutrophil phagocytosis, chemotaxis, random migration, and microbicidal activity for Candida albicans and Staphylococcus aureus. One patient showed a decreased ability to kill C. albicans at a time when she had active pneumonia due to Pneumocystis carinii. The remainder of the studies showed normal neutrophil functions. No differences were observed in the patients who had graft versus host disease [GvH] from those without GvH. These studies suggest that defects in phagocytic neutrophil function do not contribute significantly to the impaired host defenses in recipients of bone marrow transplantation.", "contents": "Neutrophil function in bone marrow transplant recipients. The neutrophil function of seven patients receiving allogeneic bone marrow transplantion was studied. Five of the patients had been transplanted for aplastic anaemia and two for acute leukaemia. Determinations were made of neutrophil phagocytosis, chemotaxis, random migration, and microbicidal activity for Candida albicans and Staphylococcus aureus. One patient showed a decreased ability to kill C. albicans at a time when she had active pneumonia due to Pneumocystis carinii. The remainder of the studies showed normal neutrophil functions. No differences were observed in the patients who had graft versus host disease [GvH] from those without GvH. These studies suggest that defects in phagocytic neutrophil function do not contribute significantly to the impaired host defenses in recipients of bone marrow transplantation."}
{"id": "PMID:15583", "title": "Effect of fat supplementation on voluntary food intake and rumen metabolism in sheep.", "content": "1. In an experiment in which a high-fat supplement was given in the dry form to lambs offered dried grass ad lib., both the voluntary intake and digestibility of the dried grass were reduced. When the high-fat supplement was given in a liquid suspension so that the rumen was by-passed, the voluntary intake and digestibility of the dried grass were not significantly altered. 2. The effect of injecting an emulsion of tallow into the rumen of sheep on rumen metabolism was studied in another experiment. Increasing the fat supplementation lowered the rate of digestion of both dried grass and cotton thread, lowered markedly the concentration of rumen ammonia, and raised the proportion of propionic acid in the rumen.", "contents": "Effect of fat supplementation on voluntary food intake and rumen metabolism in sheep. 1. In an experiment in which a high-fat supplement was given in the dry form to lambs offered dried grass ad lib., both the voluntary intake and digestibility of the dried grass were reduced. When the high-fat supplement was given in a liquid suspension so that the rumen was by-passed, the voluntary intake and digestibility of the dried grass were not significantly altered. 2. The effect of injecting an emulsion of tallow into the rumen of sheep on rumen metabolism was studied in another experiment. Increasing the fat supplementation lowered the rate of digestion of both dried grass and cotton thread, lowered markedly the concentration of rumen ammonia, and raised the proportion of propionic acid in the rumen."}
{"id": "PMID:15584", "title": "Fluorine-19 nuclear magnetic resonance studies of effects of ligands on trifluoroacetonylated supernatant aspartate transaminase.", "content": "The selective reaction of Cys-45 and -82, on the one hand, and Cys-390, on the other, with 3-bromo-1,1,1-trifluoropropanone allows for the probing of these regions of aspartate transaminase in the absence and in the presence of enzymatic ligands by 19F nuclear magnetic resonance (NMR). The 19F chemical shifts of the resonance lines differ for the three cysteines and so does their behavior with pH changes. The resonance signals with chemical shifts at 615 and 800 Hz upfield from trifluoroacetic acid correspond to modified cysteine-82 and -45 and have tentatively been assigned in this order. The 615-Hz resonance is affected by pH changes that fit best the influence of a single ionizing residue. On the 800-Hz line, the pH changes appear to be the influence of a minimum of two ionizing residues. The 19F resonance from modified Cys-390 is pH independent in the pH range 5-9 for the pyridoxal phosphate, pyridoxamine phosphate, and apoenzyme forms of the enzyme. Occupation of the active site by a quasi-enzyme-substrate complex, trifluoromethionine pyridoxyl phosphate, affects the 19F chemical shift of modified Cys-390, making it pH dependent with a pK value of 8.4. The 19F NMR properties of the pyridoxal form of Cys-390-modified enzyme can be used to monitor some ligand interactions with the active-center region. Addition of alpha-ketoglutarate or succinate to the ketone labeled enzyme causes a decrease in the resonance line width, and titrations show that this procedure is a good method with which to study the affinity of the enzyme for these ligands. The interpretation of the chemical shift and line-width characteristics of the 19F resonance arising from Cys-390 are most consistent with a model in which the region around this residue seems to be affected by conformational changes arising from substrate binding  to the active-center subsites in productive (covalent) manner. Nonproductive complexes which possess fast ligand-protein exchange, such as those between alpha-ketoglutarate or succinate with the pyridoxal phosphate form of the enzyme, may result only in a greater degree of freedom for Cys-390.", "contents": "Fluorine-19 nuclear magnetic resonance studies of effects of ligands on trifluoroacetonylated supernatant aspartate transaminase. The selective reaction of Cys-45 and -82, on the one hand, and Cys-390, on the other, with 3-bromo-1,1,1-trifluoropropanone allows for the probing of these regions of aspartate transaminase in the absence and in the presence of enzymatic ligands by 19F nuclear magnetic resonance (NMR). The 19F chemical shifts of the resonance lines differ for the three cysteines and so does their behavior with pH changes. The resonance signals with chemical shifts at 615 and 800 Hz upfield from trifluoroacetic acid correspond to modified cysteine-82 and -45 and have tentatively been assigned in this order. The 615-Hz resonance is affected by pH changes that fit best the influence of a single ionizing residue. On the 800-Hz line, the pH changes appear to be the influence of a minimum of two ionizing residues. The 19F resonance from modified Cys-390 is pH independent in the pH range 5-9 for the pyridoxal phosphate, pyridoxamine phosphate, and apoenzyme forms of the enzyme. Occupation of the active site by a quasi-enzyme-substrate complex, trifluoromethionine pyridoxyl phosphate, affects the 19F chemical shift of modified Cys-390, making it pH dependent with a pK value of 8.4. The 19F NMR properties of the pyridoxal form of Cys-390-modified enzyme can be used to monitor some ligand interactions with the active-center region. Addition of alpha-ketoglutarate or succinate to the ketone labeled enzyme causes a decrease in the resonance line width, and titrations show that this procedure is a good method with which to study the affinity of the enzyme for these ligands. The interpretation of the chemical shift and line-width characteristics of the 19F resonance arising from Cys-390 are most consistent with a model in which the region around this residue seems to be affected by conformational changes arising from substrate binding  to the active-center subsites in productive (covalent) manner. Nonproductive complexes which possess fast ligand-protein exchange, such as those between alpha-ketoglutarate or succinate with the pyridoxal phosphate form of the enzyme, may result only in a greater degree of freedom for Cys-390."}
{"id": "PMID:15585", "title": "Evidence for a critical glutamyl and an aspartyl residue in the function of pig heart diphosphopyridine nucleotide dependent isocitrate dehydrogenase.", "content": "The pH dependence of the maximum velocity of the reaction catalyzed by diphosphopyridine nucleotide (DPN) dependent isocitrate dehydrogenase indicates the requirement for the basic form of an ionizable group in the enzyme-substrate complex with a pK of 6.6. This pK is unaltered from 10 to 33 degrees C, suggesting the ionization of a carboxyl rather than an imidazolium ion. The enzyme is inactivated upon incubation with 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide in the presence of glycinamide or glycine ethyl ester. This inactivation is dependent on pH and the rate constant (k) increases as the pH is decreased in the range 7.3 to 6.25. A plot of 1/(H+) vs. 1/k suggests that the enzyme is inactivated as a result of the modification of a single ionizable group in this pH range. The coenzyme DPN and substrate alpha-ketoglutarate do not affect the rate of inactivation. In contrast, manganous ion (2 mM) and isocitrate (60 mM) produce a sevenfold decrease in the rate constant. The allosteric activator ADP (1 mM) does not itself influence the rate of inactivation; however, it reduces the concentration of Mn2+ (1 mM) and isocitrate (20 mM) required to produce the same decrease in the inactivation constant. These observations imply that the modification occurs at the substrate-binding site. Experiments employing [1-14C]glycine ethyl ester show a net incorporation of 2 mol of glycine ethyl ester per subunit (40 000), concomitant with the complete inactivation of the enzyme. The radioactive modified enzyme, after removal of excess reagent by dialysis, was exhaustively digested with proteolytic enzymes. High voltage electrophoretic analyses of the hydrolysate at pH 6.4 and 3.5 yield two major radioactive spots with approximately equal intensity, which correspond to gamma-glutamylglycine and beta-aspartylglycine, the ultimate products of reaction with glutamic and aspartic acids, respectively. Modification in the presence of manganous ion and isocitrate results in significant reduction in the incorporation of radioactivity into the two dipeptides. These results suggest that carbodiimide attacks one glutamyl and one aspartyl residue per subunit of the enzyme and that the integrity of these residues is crucial for the enzymatic activity.", "contents": "Evidence for a critical glutamyl and an aspartyl residue in the function of pig heart diphosphopyridine nucleotide dependent isocitrate dehydrogenase. The pH dependence of the maximum velocity of the reaction catalyzed by diphosphopyridine nucleotide (DPN) dependent isocitrate dehydrogenase indicates the requirement for the basic form of an ionizable group in the enzyme-substrate complex with a pK of 6.6. This pK is unaltered from 10 to 33 degrees C, suggesting the ionization of a carboxyl rather than an imidazolium ion. The enzyme is inactivated upon incubation with 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide in the presence of glycinamide or glycine ethyl ester. This inactivation is dependent on pH and the rate constant (k) increases as the pH is decreased in the range 7.3 to 6.25. A plot of 1/(H+) vs. 1/k suggests that the enzyme is inactivated as a result of the modification of a single ionizable group in this pH range. The coenzyme DPN and substrate alpha-ketoglutarate do not affect the rate of inactivation. In contrast, manganous ion (2 mM) and isocitrate (60 mM) produce a sevenfold decrease in the rate constant. The allosteric activator ADP (1 mM) does not itself influence the rate of inactivation; however, it reduces the concentration of Mn2+ (1 mM) and isocitrate (20 mM) required to produce the same decrease in the inactivation constant. These observations imply that the modification occurs at the substrate-binding site. Experiments employing [1-14C]glycine ethyl ester show a net incorporation of 2 mol of glycine ethyl ester per subunit (40 000), concomitant with the complete inactivation of the enzyme. The radioactive modified enzyme, after removal of excess reagent by dialysis, was exhaustively digested with proteolytic enzymes. High voltage electrophoretic analyses of the hydrolysate at pH 6.4 and 3.5 yield two major radioactive spots with approximately equal intensity, which correspond to gamma-glutamylglycine and beta-aspartylglycine, the ultimate products of reaction with glutamic and aspartic acids, respectively. Modification in the presence of manganous ion and isocitrate results in significant reduction in the incorporation of radioactivity into the two dipeptides. These results suggest that carbodiimide attacks one glutamyl and one aspartyl residue per subunit of the enzyme and that the integrity of these residues is crucial for the enzymatic activity."}
{"id": "PMID:15586", "title": "Binding rates, O--S substitution effects, and the pH dependence of chymotrypsin reactions.", "content": "The pH dependence for acylation of alpha-chymotrypsin by N-acetyltryptophan p-nitrophenyl-, p-nitrothiophenyl-, ethyl-, and thiolethyl esters has been studied by the stopped-flow technique. Values for the acylation rate constant, k2, and the binding constant, KS, were obtained by using measurements of phenolate release, for the p-nitrophenyl esters, and proflavin displacement, for the ethyl esters. The oxygen esters tested have slightly higher k2 values, and substantially higher KS values relative to the analogous thiol esters. Whereas k2/KS for the thiolethyl ester is higher than that for the analogous oxygen ester, the k2/KS values for oxy- and thio-p-nitrophenyl esters are nearly identical. These data are interpreted to indicate rate-determining formation of a tetrahedral intermediate in acylation of alpha-chymotrypsin by p-nitrophenyl esters, and rate-determining breakdown of such an intermediate in the case of the ethyl esters. It is also concluded that the oxygen to sulfur substitution causes a substantial increase in the proportion of nonproductive binding in these substrates. pH dependent k2 and KS values were used to calculate values for k1 and k-1, the binding and debinding rate constants for the two p-nitrophenyl compounds. This is the first such calculation based on experimentally determined acylation rate constants.", "contents": "Binding rates, O--S substitution effects, and the pH dependence of chymotrypsin reactions. The pH dependence for acylation of alpha-chymotrypsin by N-acetyltryptophan p-nitrophenyl-, p-nitrothiophenyl-, ethyl-, and thiolethyl esters has been studied by the stopped-flow technique. Values for the acylation rate constant, k2, and the binding constant, KS, were obtained by using measurements of phenolate release, for the p-nitrophenyl esters, and proflavin displacement, for the ethyl esters. The oxygen esters tested have slightly higher k2 values, and substantially higher KS values relative to the analogous thiol esters. Whereas k2/KS for the thiolethyl ester is higher than that for the analogous oxygen ester, the k2/KS values for oxy- and thio-p-nitrophenyl esters are nearly identical. These data are interpreted to indicate rate-determining formation of a tetrahedral intermediate in acylation of alpha-chymotrypsin by p-nitrophenyl esters, and rate-determining breakdown of such an intermediate in the case of the ethyl esters. It is also concluded that the oxygen to sulfur substitution causes a substantial increase in the proportion of nonproductive binding in these substrates. pH dependent k2 and KS values were used to calculate values for k1 and k-1, the binding and debinding rate constants for the two p-nitrophenyl compounds. This is the first such calculation based on experimentally determined acylation rate constants."}
{"id": "PMID:15587", "title": "Comparison of the biosynthetic and biodegradative ornithine decarboxylases of Escherichia coli.", "content": "Biosynthetic ornithine decarboxylase was purified 4300-fold from Escherichia coli to a purity of approximately 85% as judged by polyacrylamide gel electrophoresis. The enzyme showed hyperbolic kinetics with a Km of 5.6 mM for ornithine and 1.0 micronM for pyridoxal phosphate and it was competitively inhibited by putrescine and spermidine. The biosynthetic decarboxylase was compared with the biodegradative ornithine decarboxylase [Applebaum, D., et al. (1975), Biochemistry 14, 3675]. Both enzymes were dimers of 80 000-82 000 molecular weight and exhibited similar kinetic properties. However, they differed significantly in other respects. The pH optimum of the biosynthetic enzyme was 8.1, compared with 6.9 for the biodegradative. Both enzymes were activated by nucleotides, but with different specificity. Antibody to the purified biodegradative ornithine decarboxylase did not cross-react with the biosynthetic enzyme. The evolutionary relationship of these two decarboxylases to the other amino acid decarboxylases of E. coli is discussed.", "contents": "Comparison of the biosynthetic and biodegradative ornithine decarboxylases of Escherichia coli. Biosynthetic ornithine decarboxylase was purified 4300-fold from Escherichia coli to a purity of approximately 85% as judged by polyacrylamide gel electrophoresis. The enzyme showed hyperbolic kinetics with a Km of 5.6 mM for ornithine and 1.0 micronM for pyridoxal phosphate and it was competitively inhibited by putrescine and spermidine. The biosynthetic decarboxylase was compared with the biodegradative ornithine decarboxylase [Applebaum, D., et al. (1975), Biochemistry 14, 3675]. Both enzymes were dimers of 80 000-82 000 molecular weight and exhibited similar kinetic properties. However, they differed significantly in other respects. The pH optimum of the biosynthetic enzyme was 8.1, compared with 6.9 for the biodegradative. Both enzymes were activated by nucleotides, but with different specificity. Antibody to the purified biodegradative ornithine decarboxylase did not cross-react with the biosynthetic enzyme. The evolutionary relationship of these two decarboxylases to the other amino acid decarboxylases of E. coli is discussed."}
{"id": "PMID:15588", "title": "An investigation of heavy meromyosin-ADP binding equilibria by proton release measurements.", "content": "The interaction of magnesium-ADP with skeletal muscle heavy meromyosin has been studied by measuring the accompanying release of protons. Total pH changes of the order of 0.03 were involved, and measurements were performed with a discrimination of some ten-thousandths of a pH unit. At pH 8.0 and 25 degrees C about 0.5 mol of protons per mol of heavy meromyosin is released at saturation. A stoichiometry of binding close to 2 mol of ADP per mol of protein was found, with a binding constant, obtained from the proton release titration curve (pH 8.0, 25 degrees C), of 2 X 10(5) M-1. At 5 degrees C the release of protons per mole is slightly greater, and the binding constant is somewhat increased, reflecting a negative enthalpy of binding. Similar proton release behavior is observed in the presence of manganous ions in place of magnesium. The liberation of protons is thus unrelated to the temperature-dependent isomerization of myosin in the presence of substrate. Alkylation of a reactive thiol group (SH1) does not change the proton liberation at pH 8.0. From the pH dependence of proton release, the association constant of heavy meromyosin with magnesium-ADP at other pH values can be inferred and shows an appreciable rise as the pH increases. The pH-proton release profile also allows the pK of the ionizing groups perturbed by the ligand to be deduced. At least two groups ionizing above pH 7 and one below are involved. Their pK's in the unperturbed state are assigned as 8.5, 9.3, and about 6.6, respectively; they are displaced in the complex to about 8.0, 9.1, and 6.3. A relation to the pH-activity profile of myosin ATPase is indicated. The pH-proton release profile is somewhat changed when the SH1 group is alkylated. Measurements with potassium-ADP, in the absence of magnesium, show that at pH 8.0 there is no proton release but rather a sizeable proton absorption (about 0.5 mol of protons per mol of heavy meromyosin). The association constant derived from the titration curves (pH 8.0, 25 degrees C) is 3 X 10(4) M-1.", "contents": "An investigation of heavy meromyosin-ADP binding equilibria by proton release measurements. The interaction of magnesium-ADP with skeletal muscle heavy meromyosin has been studied by measuring the accompanying release of protons. Total pH changes of the order of 0.03 were involved, and measurements were performed with a discrimination of some ten-thousandths of a pH unit. At pH 8.0 and 25 degrees C about 0.5 mol of protons per mol of heavy meromyosin is released at saturation. A stoichiometry of binding close to 2 mol of ADP per mol of protein was found, with a binding constant, obtained from the proton release titration curve (pH 8.0, 25 degrees C), of 2 X 10(5) M-1. At 5 degrees C the release of protons per mole is slightly greater, and the binding constant is somewhat increased, reflecting a negative enthalpy of binding. Similar proton release behavior is observed in the presence of manganous ions in place of magnesium. The liberation of protons is thus unrelated to the temperature-dependent isomerization of myosin in the presence of substrate. Alkylation of a reactive thiol group (SH1) does not change the proton liberation at pH 8.0. From the pH dependence of proton release, the association constant of heavy meromyosin with magnesium-ADP at other pH values can be inferred and shows an appreciable rise as the pH increases. The pH-proton release profile also allows the pK of the ionizing groups perturbed by the ligand to be deduced. At least two groups ionizing above pH 7 and one below are involved. Their pK's in the unperturbed state are assigned as 8.5, 9.3, and about 6.6, respectively; they are displaced in the complex to about 8.0, 9.1, and 6.3. A relation to the pH-activity profile of myosin ATPase is indicated. The pH-proton release profile is somewhat changed when the SH1 group is alkylated. Measurements with potassium-ADP, in the absence of magnesium, show that at pH 8.0 there is no proton release but rather a sizeable proton absorption (about 0.5 mol of protons per mol of heavy meromyosin). The association constant derived from the titration curves (pH 8.0, 25 degrees C) is 3 X 10(4) M-1."}
{"id": "PMID:15589", "title": "Effects of neurotoxins (veratridine, sea anemone toxin, tetrodotoxin) on transmitter accumulation and release by nerve terminals in vitro.", "content": "Two of the tree toxic compounds used in this work, veratridine and the sea anemone toxin, provoke neurotransmitter release from synaptosomes; the third one, tetrodotoxin, prevents the action of both veratridine and the sea anemone toxin. The half-maximum effects of veratridine and sea anemone toxin actions on synaptosomes are K0.5 = 10 and 0.02 micronM, respectively. Although veratridine and the sea anemone toxin similarly provoke neurotransmitter release, they act on different receptor structures in the membrane. Tetrodotoxin antagonizes the effects of both veratridine and the sea anemone toxin. The half-maximum inhibitory concentration of tetrodotoxin is K0.5 = 4 nM for veratridine and 7.9 nM for ATXII. It is very similar to the dissociation constant measured from direct binding experiments with the radioactive toxin. The analysis of this antagonistic action offers an easy in vitro assay for tetrodotoxin interaction with its receptor.", "contents": "Effects of neurotoxins (veratridine, sea anemone toxin, tetrodotoxin) on transmitter accumulation and release by nerve terminals in vitro. Two of the tree toxic compounds used in this work, veratridine and the sea anemone toxin, provoke neurotransmitter release from synaptosomes; the third one, tetrodotoxin, prevents the action of both veratridine and the sea anemone toxin. The half-maximum effects of veratridine and sea anemone toxin actions on synaptosomes are K0.5 = 10 and 0.02 micronM, respectively. Although veratridine and the sea anemone toxin similarly provoke neurotransmitter release, they act on different receptor structures in the membrane. Tetrodotoxin antagonizes the effects of both veratridine and the sea anemone toxin. The half-maximum inhibitory concentration of tetrodotoxin is K0.5 = 4 nM for veratridine and 7.9 nM for ATXII. It is very similar to the dissociation constant measured from direct binding experiments with the radioactive toxin. The analysis of this antagonistic action offers an easy in vitro assay for tetrodotoxin interaction with its receptor."}
{"id": "PMID:15590", "title": "Purification and characterization of a plasminogen activator secreted by cultured human pancreatic carcinoma cells.", "content": "A plasminogen activator secreted by cultured human pancreatic carcinoma (Mia PaCa-2) cells has been purified to apparent homogeneity by procedures including Sepharose-L-arginine methyl ester affinity chromatography, Sephadex G-200 gel filtration, isoelectric focusing, and sodium dodecyl sulfate gel electrophoresis. The plasminogen activator shares many properties with urokinase including: molecular weight (55 000), isoelectric point (8.7), heat stability (60 degrees C, 30 min), PH stability (1.5-10), and its mode of activation of plasminogen. The intracellular enzyme is membrane bound and can be solubilized by detergent. Solubilized activator has a molecular weight similar to that of the secreted enzyme as determined by sodium dodecyl sulfate gel electrophoresis. The production of plasminogen activator by Mia PaCa-2 cells is totally inhibited by actinomycin D and cycloheximide.", "contents": "Purification and characterization of a plasminogen activator secreted by cultured human pancreatic carcinoma cells. A plasminogen activator secreted by cultured human pancreatic carcinoma (Mia PaCa-2) cells has been purified to apparent homogeneity by procedures including Sepharose-L-arginine methyl ester affinity chromatography, Sephadex G-200 gel filtration, isoelectric focusing, and sodium dodecyl sulfate gel electrophoresis. The plasminogen activator shares many properties with urokinase including: molecular weight (55 000), isoelectric point (8.7), heat stability (60 degrees C, 30 min), PH stability (1.5-10), and its mode of activation of plasminogen. The intracellular enzyme is membrane bound and can be solubilized by detergent. Solubilized activator has a molecular weight similar to that of the secreted enzyme as determined by sodium dodecyl sulfate gel electrophoresis. The production of plasminogen activator by Mia PaCa-2 cells is totally inhibited by actinomycin D and cycloheximide."}
{"id": "PMID:15591", "title": "Correlation of redox levels of component electron carriers with total electron flux in an electron-transport system. P-700 and the photoreduction of NADP+ in chloroplast fragments.", "content": "A mathematical analysis is described which measures the effects of actinic light intensity and concentration of an artificial electron donor on the steady-state light-induced redox level of a reaction-center pigment (e.g. P-700) and on the overall light-induced electron flux (e.g. reduction of NADP+). The analysis led to a formulation (somewhat similar to the Michaelis-Menten equation for enzyme kinetics) in which a parameter, I1/2, is defined as the actinic light intensity that, at a given concentration of electron donro, renders the reaction-center pigment half oxidized and half reduced. To determine the role of a presumed reaction-center pigment, I1/2 is compared with another parameter, equivalent to I1/2, that is obtained independently of the reaciton-center pigment by measuring the effect of actinic light intensity and concentration of electron donor on the overall electron flow. The theory was tested and validated in a model system with spinach Photosystem I chloroplast fragments by measurements of photooxidation of P-700 and light-induced reduction of NADP+ by reduced 2,6-dichlorophenolindophenol. A possible extension of this mathematical analysis to more general electron-transport systems is discussed.", "contents": "Correlation of redox levels of component electron carriers with total electron flux in an electron-transport system. P-700 and the photoreduction of NADP+ in chloroplast fragments. A mathematical analysis is described which measures the effects of actinic light intensity and concentration of an artificial electron donor on the steady-state light-induced redox level of a reaction-center pigment (e.g. P-700) and on the overall light-induced electron flux (e.g. reduction of NADP+). The analysis led to a formulation (somewhat similar to the Michaelis-Menten equation for enzyme kinetics) in which a parameter, I1/2, is defined as the actinic light intensity that, at a given concentration of electron donro, renders the reaction-center pigment half oxidized and half reduced. To determine the role of a presumed reaction-center pigment, I1/2 is compared with another parameter, equivalent to I1/2, that is obtained independently of the reaciton-center pigment by measuring the effect of actinic light intensity and concentration of electron donor on the overall electron flow. The theory was tested and validated in a model system with spinach Photosystem I chloroplast fragments by measurements of photooxidation of P-700 and light-induced reduction of NADP+ by reduced 2,6-dichlorophenolindophenol. A possible extension of this mathematical analysis to more general electron-transport systems is discussed."}
{"id": "PMID:15592", "title": "The effect of physiologically occurring cations upon aequorin light emission. Determination of the binding constants.", "content": "1. The effect of K+, Na+, Mg2+ and pH upon the rate of aequorin utilization has been investigated in the presence of Ca2+. 2. The aequorin light emission in a medium simulating the in vivo cationic conditions for barnacle muscle fibres indicates that two Ca2+ are apparently involved in this process for free calcium concentrations higher than approx. 10(-5) M. However, for free calcium concentrations lower than 10(-6) M, the intensity of light emitted by aequorin shows a steeper dependency upon [Ca2+] than the square low relationship, indicating that a third Ca2+ should be involved in the process of aequorin light emission, as it has been previously predicted (Moisescu, D.G., Ashley, C.C. and Campbell, A.K. (1975) Biochim. Biophys. Acta. 396, 133-140). 3. The inhibitory effect of physiologically occurring cations upon the aequorin light emission can be explained by the cooperative action of two cations, competing with Ca2+ for the reactive sites on aequorin. 4. At a given concentration, Na2+ was found to have a stronger inhibitory effect upon the aequoring light emission than K+. 5. The experiments indicate a strong interaction between Na+ and K+ in this inhibitory process, since for a given total concentration of monovalent cations, a mixture containing both Na+ and K+ has a larger inhibitory effect on the aequorin light response than solutions containing either Na+ or K+ alone. 6. All other interactions between K+, Na+, H+ and Mg2+ appear to be weak. 7. The reaction schemes used for the explanation of these and other published results on aequorin (Moisescu, D.G., Ashley, C.C. and Campbell, A.K. (1975) Biochim. Biophys, Acta 396, 133-140 and Blinks, J.R. (1973) Eur. J. Cardiol. 1, 135-142) are described, and the 'absolute' binding constants of all physiologically occurring cations for aequorin have been determined. 8. Based on these parameters one can make accurate quantitative predictions for the aequoring light response under a variety of ionic conditions, and this suggests that it is possible to determine absolute free calcium concentrations providing that the ionic composition of the solutions is known, and that the relative rate of aequorin utilization is higher than 0.005.", "contents": "The effect of physiologically occurring cations upon aequorin light emission. Determination of the binding constants. 1. The effect of K+, Na+, Mg2+ and pH upon the rate of aequorin utilization has been investigated in the presence of Ca2+. 2. The aequorin light emission in a medium simulating the in vivo cationic conditions for barnacle muscle fibres indicates that two Ca2+ are apparently involved in this process for free calcium concentrations higher than approx. 10(-5) M. However, for free calcium concentrations lower than 10(-6) M, the intensity of light emitted by aequorin shows a steeper dependency upon [Ca2+] than the square low relationship, indicating that a third Ca2+ should be involved in the process of aequorin light emission, as it has been previously predicted (Moisescu, D.G., Ashley, C.C. and Campbell, A.K. (1975) Biochim. Biophys. Acta. 396, 133-140). 3. The inhibitory effect of physiologically occurring cations upon the aequorin light emission can be explained by the cooperative action of two cations, competing with Ca2+ for the reactive sites on aequorin. 4. At a given concentration, Na2+ was found to have a stronger inhibitory effect upon the aequoring light emission than K+. 5. The experiments indicate a strong interaction between Na+ and K+ in this inhibitory process, since for a given total concentration of monovalent cations, a mixture containing both Na+ and K+ has a larger inhibitory effect on the aequorin light response than solutions containing either Na+ or K+ alone. 6. All other interactions between K+, Na+, H+ and Mg2+ appear to be weak. 7. The reaction schemes used for the explanation of these and other published results on aequorin (Moisescu, D.G., Ashley, C.C. and Campbell, A.K. (1975) Biochim. Biophys, Acta 396, 133-140 and Blinks, J.R. (1973) Eur. J. Cardiol. 1, 135-142) are described, and the 'absolute' binding constants of all physiologically occurring cations for aequorin have been determined. 8. Based on these parameters one can make accurate quantitative predictions for the aequoring light response under a variety of ionic conditions, and this suggests that it is possible to determine absolute free calcium concentrations providing that the ionic composition of the solutions is known, and that the relative rate of aequorin utilization is higher than 0.005."}
{"id": "PMID:15593", "title": "Pathways of silicomolybdate photoreduction and associated photophosphorylation in tobacco chloroplasts.", "content": "Three sites of silicomolybdate reduction in the electron transport chain of isolated tobacco chloroplasts are described. The relative participation of these sites is greatly influenced by the particular reaction conditions. One site (the only site when the reaction medium contains high concentrations of bovine serum albumin (greater than 5 mg/ml) is associated with Photosystem I, since it supports phosphorylation with a P/e2 value close to 1 and the reaction is totally sensitive to both plastocyanin inhibitors and 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Two other sites of silicomolybdate reduction are associated with Photosystem II. One site is 3-(3,4-dichlorophenyl)-1,1-dimethylurea insensitive and supports phosphorylation when the reaction mixture contains dimethyl sulfoxide and glycerol (protective agents). The P/e2 value routinely observed is about 0.2. Bovine serum albumin (1-2 mg/ml) can also act as a protective agent, but the efficiency of Photosystem II phosphorylation observed is lower. Silicomolybdate reduction supports virtually no phosphorylation, regardless of the reduction pathway, when the reaction mixture contains no protective agents. This is due to irreversible uncoupling by silicomolybdate itself. The silicomolybdate uncoupling is potentiated by high salt concentrations even if the presence of protective agents. Exposure of chloroplasts to silicomolybdate in the absence of protective agents rapidly inactivates both photosystems.", "contents": "Pathways of silicomolybdate photoreduction and associated photophosphorylation in tobacco chloroplasts. Three sites of silicomolybdate reduction in the electron transport chain of isolated tobacco chloroplasts are described. The relative participation of these sites is greatly influenced by the particular reaction conditions. One site (the only site when the reaction medium contains high concentrations of bovine serum albumin (greater than 5 mg/ml) is associated with Photosystem I, since it supports phosphorylation with a P/e2 value close to 1 and the reaction is totally sensitive to both plastocyanin inhibitors and 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Two other sites of silicomolybdate reduction are associated with Photosystem II. One site is 3-(3,4-dichlorophenyl)-1,1-dimethylurea insensitive and supports phosphorylation when the reaction mixture contains dimethyl sulfoxide and glycerol (protective agents). The P/e2 value routinely observed is about 0.2. Bovine serum albumin (1-2 mg/ml) can also act as a protective agent, but the efficiency of Photosystem II phosphorylation observed is lower. Silicomolybdate reduction supports virtually no phosphorylation, regardless of the reduction pathway, when the reaction mixture contains no protective agents. This is due to irreversible uncoupling by silicomolybdate itself. The silicomolybdate uncoupling is potentiated by high salt concentrations even if the presence of protective agents. Exposure of chloroplasts to silicomolybdate in the absence of protective agents rapidly inactivates both photosystems."}
{"id": "PMID:15594", "title": "Adenine nucleotide transport in sonic submitochondrial particles. Kinetic properties and binding of specific inhibitors.", "content": "1. A procedure for preparation of sonic submitochondrial particles competent for adenine nucleotide transport is described. ADP or ATP transport was assayed, in the presence of oligomycin, in a saline medium made of 0.125 M KCl, 1 mM EDTA, 10 mM 4-morpholinopropane sulfonic acid buffer, pH 6.5. 2. Sonic particles transport ADP and ATP by an exchange diffusion process. Externally added ADP (or ATP) is exchanged with internal ADP and ATP with a stoichiometry of one to one. The V value for ADP transport 5 degrees C was between 2 and 3 nmol/min per mg protein. 3. The transport system in sonic particles is specific for ADP and ATP. It is strongly dependent on temperature. The activation energy between 0 and 9 degrees C is approx. 35 kcal/mol. The optimum pH is 6.5, 4, Like in intact mitochondria, externally added ADP is transported into sonic particles faster at a given concentration than externally added ATP. The V value for ADP transport is 1.5-2 times higher than the V value for ATP transport. 5. The transition from the energized to the deenergized state in sonic particles results in a decrease of the pH gradient across the membrane (internal pH less than external pH) and in a 2-4 fold increase in the Km value for ATP. This latter effect is opposite that found for transport of added ATP in intact mitochondria (Souverijn, J.H.M., Huisman, L.A., Rosing J. and Kemp, Jr., A. (1973) Biochim. Biophys. Acta 305, 185-198). Energization has no effect on the V value of ATP transport in sonic particles. 6. In contrast to intact mitochondria, inhibition of ADP transport in sonic particles by bongkrekic acid does not have any lag-time and does not depend on pH. The inhibition caused by bongkrekic acid is a mixed type inhibition with a Ki value of 1.2 micronM. Atractyloside and carboxyatractyloside do not inhibit ADP transport in sonic particles, unless the particles have been preloaded with these inhibitors during the sonication. 7. Palmityl-CoA added to sonic particles inhibits efficiently ADP transport. The mixed type inhibition found with palmityl-CoA has a Ki value of 1.6 micronM. 8. [3H]Bongkrekic acid binds to sonic particles readily and with high affinity. Bongkrekic acic binding to sonic particles does not depend on pH and it has a saturation plateau, corresponding approximately to 1.3 mol of site per mol of cytochrome a. The number of [3H]atracytloside binding sites is much lower (one-fifth of the bongkrekic acid). External carboxyatractyloside does not compete with [3H]bongkrekic acid for binding to sonic particles. However, when carboxyatractyloside is present inside the particles, it inhibits the binding of [3H]bongkrekic acid.", "contents": "Adenine nucleotide transport in sonic submitochondrial particles. Kinetic properties and binding of specific inhibitors. 1. A procedure for preparation of sonic submitochondrial particles competent for adenine nucleotide transport is described. ADP or ATP transport was assayed, in the presence of oligomycin, in a saline medium made of 0.125 M KCl, 1 mM EDTA, 10 mM 4-morpholinopropane sulfonic acid buffer, pH 6.5. 2. Sonic particles transport ADP and ATP by an exchange diffusion process. Externally added ADP (or ATP) is exchanged with internal ADP and ATP with a stoichiometry of one to one. The V value for ADP transport 5 degrees C was between 2 and 3 nmol/min per mg protein. 3. The transport system in sonic particles is specific for ADP and ATP. It is strongly dependent on temperature. The activation energy between 0 and 9 degrees C is approx. 35 kcal/mol. The optimum pH is 6.5, 4, Like in intact mitochondria, externally added ADP is transported into sonic particles faster at a given concentration than externally added ATP. The V value for ADP transport is 1.5-2 times higher than the V value for ATP transport. 5. The transition from the energized to the deenergized state in sonic particles results in a decrease of the pH gradient across the membrane (internal pH less than external pH) and in a 2-4 fold increase in the Km value for ATP. This latter effect is opposite that found for transport of added ATP in intact mitochondria (Souverijn, J.H.M., Huisman, L.A., Rosing J. and Kemp, Jr., A. (1973) Biochim. Biophys. Acta 305, 185-198). Energization has no effect on the V value of ATP transport in sonic particles. 6. In contrast to intact mitochondria, inhibition of ADP transport in sonic particles by bongkrekic acid does not have any lag-time and does not depend on pH. The inhibition caused by bongkrekic acid is a mixed type inhibition with a Ki value of 1.2 micronM. Atractyloside and carboxyatractyloside do not inhibit ADP transport in sonic particles, unless the particles have been preloaded with these inhibitors during the sonication. 7. Palmityl-CoA added to sonic particles inhibits efficiently ADP transport. The mixed type inhibition found with palmityl-CoA has a Ki value of 1.6 micronM. 8. [3H]Bongkrekic acid binds to sonic particles readily and with high affinity. Bongkrekic acic binding to sonic particles does not depend on pH and it has a saturation plateau, corresponding approximately to 1.3 mol of site per mol of cytochrome a. The number of [3H]atracytloside binding sites is much lower (one-fifth of the bongkrekic acid). External carboxyatractyloside does not compete with [3H]bongkrekic acid for binding to sonic particles. However, when carboxyatractyloside is present inside the particles, it inhibits the binding of [3H]bongkrekic acid."}
{"id": "PMID:15595", "title": "Bioflavonoid regulation of ATPase and hexokinase activity in Ehrlich ascites cell mitochondria.", "content": "(1) The mitochondrial ATPase (EC 3.6.1.3) Ehrlich ascites cell mitochondria, was inhibited by D-glucose under physiological concentrations of ATP. The generation of ADP by the mitochondrial bound hexokinase, seems to be the reason for the D-glucose inhibitory effect. Reversal of the inhibitory effect of ADP on Ehrlich ascites cell mitochondria ATPase by an ATP-regenerating system was achieved. (2) Dissociation of mitochondrial bound hexokinase from the mitochondria eliminated the inhibitory effect of D-glucose. Rebinding of the hexokinase to the mitochondria regenerated the D-glucose inhibitory effect on Ehrlich ascites cell mitochondria ATPase. (3) Bioflavonoids such as quercetin inhibit the mitochondrial hexokinase activity, but do not change the mitochondrial ATPase activity of isolated Ehrlich ascites tumor cell mitochondria. (4) The inhibitory effect of bioflavonoids on mitochondrial bound hexokinase activity is shown to be dissociable from the ascites tumor cell mitochondria and seems to be associated with regulatory rather than catalitic sites of the enzyme.", "contents": "Bioflavonoid regulation of ATPase and hexokinase activity in Ehrlich ascites cell mitochondria. (1) The mitochondrial ATPase (EC 3.6.1.3) Ehrlich ascites cell mitochondria, was inhibited by D-glucose under physiological concentrations of ATP. The generation of ADP by the mitochondrial bound hexokinase, seems to be the reason for the D-glucose inhibitory effect. Reversal of the inhibitory effect of ADP on Ehrlich ascites cell mitochondria ATPase by an ATP-regenerating system was achieved. (2) Dissociation of mitochondrial bound hexokinase from the mitochondria eliminated the inhibitory effect of D-glucose. Rebinding of the hexokinase to the mitochondria regenerated the D-glucose inhibitory effect on Ehrlich ascites cell mitochondria ATPase. (3) Bioflavonoids such as quercetin inhibit the mitochondrial hexokinase activity, but do not change the mitochondrial ATPase activity of isolated Ehrlich ascites tumor cell mitochondria. (4) The inhibitory effect of bioflavonoids on mitochondrial bound hexokinase activity is shown to be dissociable from the ascites tumor cell mitochondria and seems to be associated with regulatory rather than catalitic sites of the enzyme."}
{"id": "PMID:15596", "title": "Phosphate transport in Micrococcus lysodeikticus.", "content": "Phosphate accumulates in Micrococcus lysodeikticus cells against a concentration gradient, by an energy-dependent process. The phosphate transport is derepressed during phosphate deprivation. The depression process is inhibited by chloramphenicol. The apparent Km of phosphate transport is  4.3 micronM. The activation energy of the transport is 21 kcal per mol in the temperature range of 0-29degrees C, and 4.9 kcal per mol between 29 and 40degrees C. The rate of the transport increases in presence of K+ and Mg2+. Arsenate is a competitive inhibitor of phosphate transport, having an apparent Ki of 6.0 micronM. Sulfhydryl reagents, respiratory inhibitors and uncouplers of oxidative phosphorylation inhibit phosphate transport.", "contents": "Phosphate transport in Micrococcus lysodeikticus. Phosphate accumulates in Micrococcus lysodeikticus cells against a concentration gradient, by an energy-dependent process. The phosphate transport is derepressed during phosphate deprivation. The depression process is inhibited by chloramphenicol. The apparent Km of phosphate transport is  4.3 micronM. The activation energy of the transport is 21 kcal per mol in the temperature range of 0-29degrees C, and 4.9 kcal per mol between 29 and 40degrees C. The rate of the transport increases in presence of K+ and Mg2+. Arsenate is a competitive inhibitor of phosphate transport, having an apparent Ki of 6.0 micronM. Sulfhydryl reagents, respiratory inhibitors and uncouplers of oxidative phosphorylation inhibit phosphate transport."}
{"id": "PMID:15597", "title": "Preparation of renal cortex basal-lateral and bursh border membranes. Localization of adenylate cyclase and guanylate cyclase activities.", "content": "Luminal brush border and contraluminal basal-lateral segments of the plasma membrane from the same kidney cortex were prepared. The brush border membrane preparation was enriched in trehalase and gamma-glutamyltranspeptidase, whereas the basal-lateral membrane preparation was enriched in (Na+ + K+1)-ATPase. However, the specific activity of (Na+ + K+)-ATPase in brush border membranes also increased relative to that in the crude plasma membrane fraction, suggesting that (Na+ + K+)-ATPase may be an intrinsic constituent of the renal brush border membrane in addition to being prevalent in the basal-lateral membrane. Adenylate cyclase had the same distribution pattern as (Na+ + K+)-ATPase, i.e. higher specific activity in basal-lateral membranes and present in brush border membranes. Adenylate cyclase in both membrane preparations was stimulated by parathyroid hormone, calcitonin, epinephrine, prostaglandins and 5'-guanylylimidodiphosphate. When the agonists were used in combination enhancements were additive. In contrast to the distribution of adenylate cyclase, guanylate cyclase was found in the cytosol and in basal-lateral membranes with a maximal specific activity (NaN3 plus Triton X-100) 10-fold that in brush border membranes. ATP enhanced guanylate cyclase activity only in basal-lateral membranes. It is proposed that guanylate cyclase, in addition to (Na+ + K+)-ATPase, be used as an enzyme \"marker\" for the renal basal-lateral membrane.", "contents": "Preparation of renal cortex basal-lateral and bursh border membranes. Localization of adenylate cyclase and guanylate cyclase activities. Luminal brush border and contraluminal basal-lateral segments of the plasma membrane from the same kidney cortex were prepared. The brush border membrane preparation was enriched in trehalase and gamma-glutamyltranspeptidase, whereas the basal-lateral membrane preparation was enriched in (Na+ + K+1)-ATPase. However, the specific activity of (Na+ + K+)-ATPase in brush border membranes also increased relative to that in the crude plasma membrane fraction, suggesting that (Na+ + K+)-ATPase may be an intrinsic constituent of the renal brush border membrane in addition to being prevalent in the basal-lateral membrane. Adenylate cyclase had the same distribution pattern as (Na+ + K+)-ATPase, i.e. higher specific activity in basal-lateral membranes and present in brush border membranes. Adenylate cyclase in both membrane preparations was stimulated by parathyroid hormone, calcitonin, epinephrine, prostaglandins and 5'-guanylylimidodiphosphate. When the agonists were used in combination enhancements were additive. In contrast to the distribution of adenylate cyclase, guanylate cyclase was found in the cytosol and in basal-lateral membranes with a maximal specific activity (NaN3 plus Triton X-100) 10-fold that in brush border membranes. ATP enhanced guanylate cyclase activity only in basal-lateral membranes. It is proposed that guanylate cyclase, in addition to (Na+ + K+)-ATPase, be used as an enzyme \"marker\" for the renal basal-lateral membrane."}
{"id": "PMID:15598", "title": "Effect of the medium pH and the cell pH upon the kinetical parameters of phosphate uptake by yeast.", "content": "1. Both the maximum rate of phosphate uptake and the Km depend upon the pH of the medium in a complex way. 2. The effect of medium pH upon the maximum rate of uptake is mainly indirect and is correlated with changes in cell pH. 3. The Km is affected by the medium pH both directly via an apparent competitive inhibition by hydroxyl anions and indirectly in a similar way as the maximum rate of uptake.", "contents": "Effect of the medium pH and the cell pH upon the kinetical parameters of phosphate uptake by yeast. 1. Both the maximum rate of phosphate uptake and the Km depend upon the pH of the medium in a complex way. 2. The effect of medium pH upon the maximum rate of uptake is mainly indirect and is correlated with changes in cell pH. 3. The Km is affected by the medium pH both directly via an apparent competitive inhibition by hydroxyl anions and indirectly in a similar way as the maximum rate of uptake."}
{"id": "PMID:15599", "title": "Pyrrolo(1,4)benzodiazepine antitumor antibiotics. In vitro interaction of anthramycin, sibiromycin and tomaymycin with DNA using specifically radiolabelled molecules.", "content": "Anthramycin, tomaymycin and sibiromycin are pyrrolo(1,4)benzodiazepine antitumor antibiotics. These compounds react with DNA and other guanine-containing polydeoxynucleotides to form covalently bound antibiotic - polydeoxynucleotide complexes. Experiments utilizing radiolabelled antibiotics have led to the following conclusions: 1. Sibiromycin reacts much faster than either anthramycin or tomaymycin with DNA. 2. At saturation binding the final antibiotic to base ratios for sibiromycin, anthramycin and tomaymycin are 1 : 8.8,1: 12.9, and 1 : 18.2, respectively. 3. No reaction with RNA or protein occurs with the pyrrolo(1,4)benzodiazepine antibiotics. 4. Sibiromycin effectively competes for the same DNA binding sites as anthramycin and tomaymycin; however, there is only partial overlap for the same binding sites between anthramycin and tomaymycin. 5. Whereas all three pyrrolo(1,4)benzodiazepine antibiotic-DNA complexes are relatively stable to alkaline conditions, their stability under acidic conditions increases in the order tomaymycin, anthramycin and sibiromycin. 6. No loss of non-exchangeable hydrogens in either the pyrrol ring or the side chains of these antibiotics occurs upon formation of their complexes with DNA. 7. Unchanged antibiotic has been demonstrated to be released upon acid treatment of the anthramycin-DNA and tomaymycin-DNA complexes. 8. A Schiff base linkage between the  antibiotics and DNA has been eliminated. The comparative reactivity of the three antibiotics towards DNA and the stability of their DNA complexes is discussed in relation to their structures. A working hypothesis for the formation of the antibiotic-DNA covalent complexes is proposed based upon the available information.", "contents": "Pyrrolo(1,4)benzodiazepine antitumor antibiotics. In vitro interaction of anthramycin, sibiromycin and tomaymycin with DNA using specifically radiolabelled molecules. Anthramycin, tomaymycin and sibiromycin are pyrrolo(1,4)benzodiazepine antitumor antibiotics. These compounds react with DNA and other guanine-containing polydeoxynucleotides to form covalently bound antibiotic - polydeoxynucleotide complexes. Experiments utilizing radiolabelled antibiotics have led to the following conclusions: 1. Sibiromycin reacts much faster than either anthramycin or tomaymycin with DNA. 2. At saturation binding the final antibiotic to base ratios for sibiromycin, anthramycin and tomaymycin are 1 : 8.8,1: 12.9, and 1 : 18.2, respectively. 3. No reaction with RNA or protein occurs with the pyrrolo(1,4)benzodiazepine antibiotics. 4. Sibiromycin effectively competes for the same DNA binding sites as anthramycin and tomaymycin; however, there is only partial overlap for the same binding sites between anthramycin and tomaymycin. 5. Whereas all three pyrrolo(1,4)benzodiazepine antibiotic-DNA complexes are relatively stable to alkaline conditions, their stability under acidic conditions increases in the order tomaymycin, anthramycin and sibiromycin. 6. No loss of non-exchangeable hydrogens in either the pyrrol ring or the side chains of these antibiotics occurs upon formation of their complexes with DNA. 7. Unchanged antibiotic has been demonstrated to be released upon acid treatment of the anthramycin-DNA and tomaymycin-DNA complexes. 8. A Schiff base linkage between the  antibiotics and DNA has been eliminated. The comparative reactivity of the three antibiotics towards DNA and the stability of their DNA complexes is discussed in relation to their structures. A working hypothesis for the formation of the antibiotic-DNA covalent complexes is proposed based upon the available information."}
{"id": "PMID:15600", "title": "Reactive carriers of immobilized compounds.", "content": "Sphericanl macroporous reactive carriers capable of forming covalent bonds with amino acids and proteins were prepared by the suspension copolymerization of 2-hydroxyethyl methacrylate, ethylene dimethacrylate and p-nitrophenyl esters of methacrylic acid and methacryloyl derivatives of glycine, beta-alanine and epsilon-aminocaproic acid. The effect of the spacer length, pH and the type of the buffer used, concentration of reactive groups in the copolymer, concentration of the ligand and the participation of the hydrolytic and aminolytic reaction of p-nitrophenyl functional groups in the attachment of glycine, D,L-phenylalanine and serumalbumin was studied. Macroporous copolymers containing reactive functional groups can be used as active enzyme carriers, if their activity is not blocked by the presence of p-nitrophenol split off in the attachment reaction.", "contents": "Reactive carriers of immobilized compounds. Sphericanl macroporous reactive carriers capable of forming covalent bonds with amino acids and proteins were prepared by the suspension copolymerization of 2-hydroxyethyl methacrylate, ethylene dimethacrylate and p-nitrophenyl esters of methacrylic acid and methacryloyl derivatives of glycine, beta-alanine and epsilon-aminocaproic acid. The effect of the spacer length, pH and the type of the buffer used, concentration of reactive groups in the copolymer, concentration of the ligand and the participation of the hydrolytic and aminolytic reaction of p-nitrophenyl functional groups in the attachment of glycine, D,L-phenylalanine and serumalbumin was studied. Macroporous copolymers containing reactive functional groups can be used as active enzyme carriers, if their activity is not blocked by the presence of p-nitrophenol split off in the attachment reaction."}
{"id": "PMID:15601", "title": "Purification of the (Na+ + K+)-adenosine triphosphatase from human renal tissue.", "content": "(Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was purified from human cadaver renal tissue and exhibited a linear reaction rate with time. 100 g of whole kidney would yield 1--3.5 mg protein with a specific activity of 50--200 mol - kg-1 - h-1 for (Na+ + K+)-ATPase. The preparation was completely inhibited by 100 micronM ouabain with a Ki of 1.8 micronM. K+-dependent phosphatase increased during purification of (Na+ + K+)-ATPase to 7.8 mol - kg-1 - h-1. There was no detectable Mg2+-ATPase in the final preparation. Sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis yielded three protein peaks of 117 000, 92 500, and 56 000 daltons. The peptide band corresponding to 92 500 daltons underwent an Na+-dependent phosphorylation with [gamma-32P]-ATP. The band at 56 000 daltons stained for glycoprotein. The Km for ATP was 0.38 mM and that for Mg2+ was 0.5 mM. The formation of ADP and inorganic phosphate from ATP was stoichiometric. The Km for Na+ in the presence of 20 mM K+ was 16 mM and the Km for K+ in the presence of 100 mM Na+ was 1.5 mM. The temperature optimum was 51degrees C and the pH optimum was 7.0. (Na+ + K+)-ATPase in whole homogenate, microsomes, and NaI-treated microsomes exhibited a slowing of reaction rate (non-linearity) with time such that the enzyme was inactive by 10--15 min of reaction. This non-linearity was eliminated during purification. The significance is discussed.", "contents": "Purification of the (Na+ + K+)-adenosine triphosphatase from human renal tissue. (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was purified from human cadaver renal tissue and exhibited a linear reaction rate with time. 100 g of whole kidney would yield 1--3.5 mg protein with a specific activity of 50--200 mol - kg-1 - h-1 for (Na+ + K+)-ATPase. The preparation was completely inhibited by 100 micronM ouabain with a Ki of 1.8 micronM. K+-dependent phosphatase increased during purification of (Na+ + K+)-ATPase to 7.8 mol - kg-1 - h-1. There was no detectable Mg2+-ATPase in the final preparation. Sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis yielded three protein peaks of 117 000, 92 500, and 56 000 daltons. The peptide band corresponding to 92 500 daltons underwent an Na+-dependent phosphorylation with [gamma-32P]-ATP. The band at 56 000 daltons stained for glycoprotein. The Km for ATP was 0.38 mM and that for Mg2+ was 0.5 mM. The formation of ADP and inorganic phosphate from ATP was stoichiometric. The Km for Na+ in the presence of 20 mM K+ was 16 mM and the Km for K+ in the presence of 100 mM Na+ was 1.5 mM. The temperature optimum was 51degrees C and the pH optimum was 7.0. (Na+ + K+)-ATPase in whole homogenate, microsomes, and NaI-treated microsomes exhibited a slowing of reaction rate (non-linearity) with time such that the enzyme was inactive by 10--15 min of reaction. This non-linearity was eliminated during purification. The significance is discussed."}
{"id": "PMID:15602", "title": "Purification and crystallization of NADP+-specific isocitrate dehydrogenase from Escherichia coli using polyethylene glycol.", "content": "A simple and rapid method is presented for purifying the NADP+-dependent isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), from Escherichia coli, which relies on fractionation of the enzyme with polyethylene glycol. The shortened preparation results in a 32% relative recovery of purified enzyme at a specific activity of 127 micronmol/min per mg of protein. The Km values for threo-DS-isocitrate, NADP+, NAD+, Mg2+ and Mn2+ are 6.4, 36, 3000, 19.7 and 2.0 micronM, respectively. The stability of the enzyme as a function of dilution and temperature are also reported. Recrystallization of the purified enzyme under different conditions readily produces a variety of single crystals. Crystals grown from ammonium sulfate solutions belong to monoclinic space group C2 with a = 125 A, b = 111 A, c = 83.5 A and beta = 108degrees 45'. Density measurements of these crystals indicate there are two 80 000-dalton dimers per asymmetric unit.", "contents": "Purification and crystallization of NADP+-specific isocitrate dehydrogenase from Escherichia coli using polyethylene glycol. A simple and rapid method is presented for purifying the NADP+-dependent isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), from Escherichia coli, which relies on fractionation of the enzyme with polyethylene glycol. The shortened preparation results in a 32% relative recovery of purified enzyme at a specific activity of 127 micronmol/min per mg of protein. The Km values for threo-DS-isocitrate, NADP+, NAD+, Mg2+ and Mn2+ are 6.4, 36, 3000, 19.7 and 2.0 micronM, respectively. The stability of the enzyme as a function of dilution and temperature are also reported. Recrystallization of the purified enzyme under different conditions readily produces a variety of single crystals. Crystals grown from ammonium sulfate solutions belong to monoclinic space group C2 with a = 125 A, b = 111 A, c = 83.5 A and beta = 108degrees 45'. Density measurements of these crystals indicate there are two 80 000-dalton dimers per asymmetric unit."}
{"id": "PMID:15603", "title": "Glyceraldehyde-3-phosphate dehydrogenase of Scenedesmus obliquus. Effects of dithiothreitol and nucleotide on coenzyme specificity.", "content": "NADH-dependent glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.--) of the photosynthetic alga Scenedesmus obliquus is converted to an NADPH specific form by incubation with dithiothreitol. The change in nucleotide specificity is accompanied by a reduction in the molecular weight of the enzyme from 550 000 to 140 000. Prolonged incubation with dithiothreitol results in the further dissociation of the enzyme to an inactive 70 000 dalton species. The 140 000 dalton, NADPH-specific enzyme is stabilized against dissociation and inactivation by the presence of NAD(H) or NADP(H). Optimum stimulation of NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase activity is achieved on incubation of the NADH-specific enzyme with dithiothreitol and NADPH, or dithiothreitol and a 1,3-diphosphoglycerate generating system. The relevance of these observations to in vivo light-induced changes in the nucleotide specificity of the enzyme is discussed.", "contents": "Glyceraldehyde-3-phosphate dehydrogenase of Scenedesmus obliquus. Effects of dithiothreitol and nucleotide on coenzyme specificity. NADH-dependent glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.--) of the photosynthetic alga Scenedesmus obliquus is converted to an NADPH specific form by incubation with dithiothreitol. The change in nucleotide specificity is accompanied by a reduction in the molecular weight of the enzyme from 550 000 to 140 000. Prolonged incubation with dithiothreitol results in the further dissociation of the enzyme to an inactive 70 000 dalton species. The 140 000 dalton, NADPH-specific enzyme is stabilized against dissociation and inactivation by the presence of NAD(H) or NADP(H). Optimum stimulation of NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase activity is achieved on incubation of the NADH-specific enzyme with dithiothreitol and NADPH, or dithiothreitol and a 1,3-diphosphoglycerate generating system. The relevance of these observations to in vivo light-induced changes in the nucleotide specificity of the enzyme is discussed."}
{"id": "PMID:15604", "title": "Enzymic oxidation of 3-hydroxyxanthine to 3-hydroxyuric acid.", "content": "1. Bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) oxidises 3-hydroxyxanthine slowly to 3-hydroxyuric acid; the 1-methyl derivative of 3-hydroxyxanthine is attacked about twice as fast. 2. The pH optimum for the reaction of 2-hydroxyxanthine is near 5, i.e. the neutral form of this substrate is attacked much faster than the anion. Probably in the \"active\" form of the latter, the negative charge is located mainly in the imidazole ring, thus inhibiting nucleophilic attack at C-8.", "contents": "Enzymic oxidation of 3-hydroxyxanthine to 3-hydroxyuric acid. 1. Bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) oxidises 3-hydroxyxanthine slowly to 3-hydroxyuric acid; the 1-methyl derivative of 3-hydroxyxanthine is attacked about twice as fast. 2. The pH optimum for the reaction of 2-hydroxyxanthine is near 5, i.e. the neutral form of this substrate is attacked much faster than the anion. Probably in the \"active\" form of the latter, the negative charge is located mainly in the imidazole ring, thus inhibiting nucleophilic attack at C-8."}
{"id": "PMID:15605", "title": "The transient-state kinetics of L-glutamate dehydrogenase. pH-dependence of the burst rate parameters.", "content": "The pH dependence of the initial transient velocity of NADPH production during the burst phase of the oxidative deamination of L-glutamate by L-glutamate dehydrogenase (L-glutamate : NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3) and NADP+ has been measured by stopped-flow spectrophotometry. These studies provide evidence that the entire pH dependence below pH 8.26 arises from reaction steps contributing to V of the burst with an apparent pKa of 8.1 +/- 0.1. The data are consistent with a model in which the formation of the first enzyme-coenzyme-substrate ternary complex on the reaction path equilibrates rapidly and in which the pH-dependent steps are mechanistically close to and may include the catalytic hydrogen transfer itself. At pH 8.87, there is evidence that L-glutamate binds less tightly to the enzyme and to the enzyme-NADP+ complex than at lower pH values.", "contents": "The transient-state kinetics of L-glutamate dehydrogenase. pH-dependence of the burst rate parameters. The pH dependence of the initial transient velocity of NADPH production during the burst phase of the oxidative deamination of L-glutamate by L-glutamate dehydrogenase (L-glutamate : NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3) and NADP+ has been measured by stopped-flow spectrophotometry. These studies provide evidence that the entire pH dependence below pH 8.26 arises from reaction steps contributing to V of the burst with an apparent pKa of 8.1 +/- 0.1. The data are consistent with a model in which the formation of the first enzyme-coenzyme-substrate ternary complex on the reaction path equilibrates rapidly and in which the pH-dependent steps are mechanistically close to and may include the catalytic hydrogen transfer itself. At pH 8.87, there is evidence that L-glutamate binds less tightly to the enzyme and to the enzyme-NADP+ complex than at lower pH values."}
{"id": "PMID:15606", "title": "Cyanide formation from histidine in Chlorella. A general reaction of aromatic amino acids catalyzed by amino acid oxidase systems.", "content": "The formation of HCN from D-histidine in Chlorella vulgaris extracts is shown to be due to the combined action of a soluble protein and a particulate component. Either horse-radish peroxidase (EC 1.11.1.7) or a metal ion with redox properties can be substituted for the particulate component. Ions of manganese and vanadium are especially effective, as are o-phenanthroline complexes of iron. Cobalt ions are less active. The D-amino acid oxidase (EC 1.4.3.3) from kidney and the L-amino acid oxidase (EC 1.4.3.2) from snake venom likewise cause HCN production from histidine when supplemented with the particulate preparation from Chlorella or with peroxidase or with a redox metal ion. The stereospecificity of the amino acid oxidase determines which of the two stereoisomers of histidine is active as an HCN precursor. Though histidine is the best substrate for HCN production, other naturally occurring aromatic amino acids (viz. tyrosine, phenylalanine and tryptophan) can also serve as HCN precursors with these enzyme systems. The relative effectiveness of each substrate varies with the amino acid oxidase enzyme and with the supplement. With respect to this latter property, the particulate preparation from Chlorella behaves more like a metal ion than like peroxidase.", "contents": "Cyanide formation from histidine in Chlorella. A general reaction of aromatic amino acids catalyzed by amino acid oxidase systems. The formation of HCN from D-histidine in Chlorella vulgaris extracts is shown to be due to the combined action of a soluble protein and a particulate component. Either horse-radish peroxidase (EC 1.11.1.7) or a metal ion with redox properties can be substituted for the particulate component. Ions of manganese and vanadium are especially effective, as are o-phenanthroline complexes of iron. Cobalt ions are less active. The D-amino acid oxidase (EC 1.4.3.3) from kidney and the L-amino acid oxidase (EC 1.4.3.2) from snake venom likewise cause HCN production from histidine when supplemented with the particulate preparation from Chlorella or with peroxidase or with a redox metal ion. The stereospecificity of the amino acid oxidase determines which of the two stereoisomers of histidine is active as an HCN precursor. Though histidine is the best substrate for HCN production, other naturally occurring aromatic amino acids (viz. tyrosine, phenylalanine and tryptophan) can also serve as HCN precursors with these enzyme systems. The relative effectiveness of each substrate varies with the amino acid oxidase enzyme and with the supplement. With respect to this latter property, the particulate preparation from Chlorella behaves more like a metal ion than like peroxidase."}
{"id": "PMID:15607", "title": "A D-amino acid oxidase from Chlorella vulgaris.", "content": "A procedure has been developed for the partial purification from Chlorella vulgaris of an enzyme which catalyzes the formation of HCN from D-histidine when supplemented with peroxidase of a metal with redox properties. Some properties of the enzyme are described. Evidence is presented that the catalytic activity for HCN formation is associated with a capacity for catalyzing the oxidation of a wide variety of D-amino acids. With D-leucine, the best substrate for O2 consumption, 1 mol of ammonia is formed for half a mol of O2 consumed in the presence of catalase. An inactive apoenzyme can be obtained by acid ammonium sulfate precipitation, and reactivated by added FAD. On the basis of these criteria, the Chlorella enzyme can be classified as a D-amino acid oxidase (EC 1.4.3.3). Kidney D-amino acid oxidase and snake venom L-amino acid oxidase, which likewise form HCN from histidine on supplementation with peroxidase, have been compared with the Chlorella D-amino acid oxidase. The capacity of these enzymes for causing HCN formation from histidine is about proportional to their ability to catalyze the oxidation of histidine.", "contents": "A D-amino acid oxidase from Chlorella vulgaris. A procedure has been developed for the partial purification from Chlorella vulgaris of an enzyme which catalyzes the formation of HCN from D-histidine when supplemented with peroxidase of a metal with redox properties. Some properties of the enzyme are described. Evidence is presented that the catalytic activity for HCN formation is associated with a capacity for catalyzing the oxidation of a wide variety of D-amino acids. With D-leucine, the best substrate for O2 consumption, 1 mol of ammonia is formed for half a mol of O2 consumed in the presence of catalase. An inactive apoenzyme can be obtained by acid ammonium sulfate precipitation, and reactivated by added FAD. On the basis of these criteria, the Chlorella enzyme can be classified as a D-amino acid oxidase (EC 1.4.3.3). Kidney D-amino acid oxidase and snake venom L-amino acid oxidase, which likewise form HCN from histidine on supplementation with peroxidase, have been compared with the Chlorella D-amino acid oxidase. The capacity of these enzymes for causing HCN formation from histidine is about proportional to their ability to catalyze the oxidation of histidine."}
{"id": "PMID:15608", "title": "Allosteric and non-allosteric phosphofructokinases from Lactobacilli. Purification and properties of phosphofructokinases from L. plantarum and L. acidophilus.", "content": "Phosphofructokinase (ATP : D-fructose-6-phosphate 1 phosphotransferase, EC 2.7.1.11) from two different lactobacilli, Lactobacillus plantarum and Lactobacillus acidophilus were isolated and purified. Both enzymes have a molecular weight of 154 000 and consist of four subunits of identical size. Antisera from sheep immunized against the purified phosphofructokinase from L. plantarum showed immunologic cross reaction with the enzyme from L. acidophilus. In spite of the close molecular relationship indicated by the immunologic cross reaction, the kinetic behaviour of the two enzymes was strikingly different. Phosphofructokinase from L. plantarum showed pure Michaelis-Menten behaviour. Phosphofructokinase from L. acidophilus, however, showed sigmoidal substrate saturation curves for fructose 6-phosphate in the presence of slightly alkaline pH and high ATP concentrations; it was activated by fructose 1,6-biphosphate and inhibited by ADP. The results indicate that even enzymes which are structurally very similar may differ greatly with respect to their kinetic and regulatory properties and suggest that allosteric and non-allosteric phosphofructokinases have the same origin in evolution.", "contents": "Allosteric and non-allosteric phosphofructokinases from Lactobacilli. Purification and properties of phosphofructokinases from L. plantarum and L. acidophilus. Phosphofructokinase (ATP : D-fructose-6-phosphate 1 phosphotransferase, EC 2.7.1.11) from two different lactobacilli, Lactobacillus plantarum and Lactobacillus acidophilus were isolated and purified. Both enzymes have a molecular weight of 154 000 and consist of four subunits of identical size. Antisera from sheep immunized against the purified phosphofructokinase from L. plantarum showed immunologic cross reaction with the enzyme from L. acidophilus. In spite of the close molecular relationship indicated by the immunologic cross reaction, the kinetic behaviour of the two enzymes was strikingly different. Phosphofructokinase from L. plantarum showed pure Michaelis-Menten behaviour. Phosphofructokinase from L. acidophilus, however, showed sigmoidal substrate saturation curves for fructose 6-phosphate in the presence of slightly alkaline pH and high ATP concentrations; it was activated by fructose 1,6-biphosphate and inhibited by ADP. The results indicate that even enzymes which are structurally very similar may differ greatly with respect to their kinetic and regulatory properties and suggest that allosteric and non-allosteric phosphofructokinases have the same origin in evolution."}
{"id": "PMID:15609", "title": "Inactivation and reactivation of liver phosphorylase b kinase.", "content": "When crude rat liver preparations were incubated at 30degrees C, a gradual loss of phosphorylase kinase (ATP:phosphorylase b phosphotransferase, EC 2.7.1.38) activity was observed. This inactivation was Mg2+ dependent and was partially inhibited by sodium fluoride. Addition of Mg2+ ATP to the liver preparations, at any time throughout the incubation, caused a reactivation of the phosphorylase kinase and this was accelerated by micromolar concentrations of cyclic AMP. The reactivation process could be completely abolished by the addition of a heat stable protein kinase inhibitor, implicating cyclic AMP dependent protein kinase in the activation reaction. Both the low and the high activity forms of the enzyme required micromolar quantities of Ca2+ for full activity (KA = 0.6 micronM). The two forms exhibit quite different pH dependencies and at the physiological pH of liver (pH 7.4) their activities differed by a factor of 5-10. Conversion of the lower activity form into the higher seems to affect only the V - Km for muscle phosphorylase b (EC 2.4.1.1) was about 1 mg/ml for both enzyme forms.", "contents": "Inactivation and reactivation of liver phosphorylase b kinase. When crude rat liver preparations were incubated at 30degrees C, a gradual loss of phosphorylase kinase (ATP:phosphorylase b phosphotransferase, EC 2.7.1.38) activity was observed. This inactivation was Mg2+ dependent and was partially inhibited by sodium fluoride. Addition of Mg2+ ATP to the liver preparations, at any time throughout the incubation, caused a reactivation of the phosphorylase kinase and this was accelerated by micromolar concentrations of cyclic AMP. The reactivation process could be completely abolished by the addition of a heat stable protein kinase inhibitor, implicating cyclic AMP dependent protein kinase in the activation reaction. Both the low and the high activity forms of the enzyme required micromolar quantities of Ca2+ for full activity (KA = 0.6 micronM). The two forms exhibit quite different pH dependencies and at the physiological pH of liver (pH 7.4) their activities differed by a factor of 5-10. Conversion of the lower activity form into the higher seems to affect only the V - Km for muscle phosphorylase b (EC 2.4.1.1) was about 1 mg/ml for both enzyme forms."}
{"id": "PMID:15610", "title": "Compensational phenomena in reactivation of dimethyl- and diethylphosphoryl butyrylcholinesterases.", "content": "The thermodynamic and kinetic parameters for spontaneous and oxime reactivation of dimethyl- and diethylphosphoryl butyrylcholinesterases (acylcholine acyl-hydrolase, EC 3.1.1.8) are reported. The enthalpy and entropy changes in both the binding (deltaH0 and deltaS0) and the dephosphorylation steps (deltaH* and deltaS*) were found to be coupled, resulting in a minor variation in free energy changes (deltaG0 and deltaG*). While neither enthalpies nor entropies alone bore any relationship with the kinetic parameters KD and kR, the changes of free energies (deltaG0 and deltaG*) correlated linearly with the logarithmic values of the dissociation constants (KD) and bimolecular rate constants (kR/KD), respectively. Compensation plots of entropies versus enthalpies gave straight lines with compensation temperatures of 275 K for the binding 260 K for the dephosphorylation. Spontaneous reactivation of dimethyl phosphoryl butyrylcholinesterase was investigated at various pH values and three temperatures. It implicated two catalytic sites with values of pKi of 9.4 and 7.5, and heats of ionisation of 5.3 and 9.6 kcal - mol-1, respectively. Possible conformational alteration of the inhibited enzyme arising from the binding of oximes is discussed.", "contents": "Compensational phenomena in reactivation of dimethyl- and diethylphosphoryl butyrylcholinesterases. The thermodynamic and kinetic parameters for spontaneous and oxime reactivation of dimethyl- and diethylphosphoryl butyrylcholinesterases (acylcholine acyl-hydrolase, EC 3.1.1.8) are reported. The enthalpy and entropy changes in both the binding (deltaH0 and deltaS0) and the dephosphorylation steps (deltaH* and deltaS*) were found to be coupled, resulting in a minor variation in free energy changes (deltaG0 and deltaG*). While neither enthalpies nor entropies alone bore any relationship with the kinetic parameters KD and kR, the changes of free energies (deltaG0 and deltaG*) correlated linearly with the logarithmic values of the dissociation constants (KD) and bimolecular rate constants (kR/KD), respectively. Compensation plots of entropies versus enthalpies gave straight lines with compensation temperatures of 275 K for the binding 260 K for the dephosphorylation. Spontaneous reactivation of dimethyl phosphoryl butyrylcholinesterase was investigated at various pH values and three temperatures. It implicated two catalytic sites with values of pKi of 9.4 and 7.5, and heats of ionisation of 5.3 and 9.6 kcal - mol-1, respectively. Possible conformational alteration of the inhibited enzyme arising from the binding of oximes is discussed."}
{"id": "PMID:15611", "title": "Catalytic activity of Ntau-carboxymethylhistidine-12 ribonuclease: pH dependence.", "content": "The pH-dependence of RNAase A and of Ntau-carboxymethylhistidine-12-RNAase (ribonucleate 3'-pyrimidino-oligonucleotidohydrolase) catalysis was studied. Apparent acid dissociation constants were obtained by least squares analysis of the kinetics data. These dissociation constants were compared with pKa values of model imidazole compounds, and with pKa values of histidine residues 12 and 119 on the protein. The shapes of the kcat versus pH profiles for RNAase A and its carboxymethyl derivative are very similar, from which it is concluded that the mechanism of catalysis is closely similar in the two proteins. Apparent pKa values obtained from the kinetic data are higher for the carboxymethylated protein than for RNAase A, as are the pKa values of residues 12 and 119. The similar shifts are consistent with the conclusions that both these residues are functionally significant in native and modified enzyme, and that an unblocked tau-nitrogen on histidine-12 is not essential for activity. From the enzyme's catalytic dependence on pH, and the NMR determined pKa values we propose that histidine 12 and 119 function catalytically in their basic and acidic forms respectively.", "contents": "Catalytic activity of Ntau-carboxymethylhistidine-12 ribonuclease: pH dependence. The pH-dependence of RNAase A and of Ntau-carboxymethylhistidine-12-RNAase (ribonucleate 3'-pyrimidino-oligonucleotidohydrolase) catalysis was studied. Apparent acid dissociation constants were obtained by least squares analysis of the kinetics data. These dissociation constants were compared with pKa values of model imidazole compounds, and with pKa values of histidine residues 12 and 119 on the protein. The shapes of the kcat versus pH profiles for RNAase A and its carboxymethyl derivative are very similar, from which it is concluded that the mechanism of catalysis is closely similar in the two proteins. Apparent pKa values obtained from the kinetic data are higher for the carboxymethylated protein than for RNAase A, as are the pKa values of residues 12 and 119. The similar shifts are consistent with the conclusions that both these residues are functionally significant in native and modified enzyme, and that an unblocked tau-nitrogen on histidine-12 is not essential for activity. From the enzyme's catalytic dependence on pH, and the NMR determined pKa values we propose that histidine 12 and 119 function catalytically in their basic and acidic forms respectively."}
{"id": "PMID:15613", "title": "The activator of cerebroside sulphatase. Binding studies with enzyme and substrate demonstrating the detergent function of the activator protein.", "content": "1. Sulphatase A (cerebroside sulphatase) (EC 3.1.6.1.) and a 12-fold excess of its physiological activator protein were chromatographed together on Sephadex G-75. The elution buffer was the same as that used in the enzymic degradation of sulphatides. The two proteins were eluted in different peaks indicating that no stable complex formed. 2. Activator protein was incubated with sulphatides under conditions used favouring the sulphatase activity. Incubation solutions were then examined by electrophoresis on a polyacrylamide gel gradient. An one-to-one complex between activator and sulphatides was observed. Half maximal binding occurred with 2.5 nmol of sulphatides together with 1 or 2 nmol of activator in 100 micronl. 3. Cerebrosides as the enzymic degradation products of sulphatides, bind also to the activator protein. A ratio of one-to-one could possibly be obtained at high cerebroside concentrations. The binding to cerebrosides is less specific than that to sulphatides. A 7-fold excess of cerebrosides was necessary for half maximal binding. 4. In a mixture of sulphatides and cerebrosides the formation of the complex with the activator protein is partly inhibited. The total amount of bound lipids changed as the composition of the lipid mixture was varied. In a one-to-one mixture of the two lipids 60% of the total bound lipids are sulphatides and 40% are cerebrosides.", "contents": "The activator of cerebroside sulphatase. Binding studies with enzyme and substrate demonstrating the detergent function of the activator protein. 1. Sulphatase A (cerebroside sulphatase) (EC 3.1.6.1.) and a 12-fold excess of its physiological activator protein were chromatographed together on Sephadex G-75. The elution buffer was the same as that used in the enzymic degradation of sulphatides. The two proteins were eluted in different peaks indicating that no stable complex formed. 2. Activator protein was incubated with sulphatides under conditions used favouring the sulphatase activity. Incubation solutions were then examined by electrophoresis on a polyacrylamide gel gradient. An one-to-one complex between activator and sulphatides was observed. Half maximal binding occurred with 2.5 nmol of sulphatides together with 1 or 2 nmol of activator in 100 micronl. 3. Cerebrosides as the enzymic degradation products of sulphatides, bind also to the activator protein. A ratio of one-to-one could possibly be obtained at high cerebroside concentrations. The binding to cerebrosides is less specific than that to sulphatides. A 7-fold excess of cerebrosides was necessary for half maximal binding. 4. In a mixture of sulphatides and cerebrosides the formation of the complex with the activator protein is partly inhibited. The total amount of bound lipids changed as the composition of the lipid mixture was varied. In a one-to-one mixture of the two lipids 60% of the total bound lipids are sulphatides and 40% are cerebrosides."}
{"id": "PMID:15615", "title": "The effect of pre-incubation on trypsin kinetics at low pH.", "content": "A possible source of discrepancy between kinetic and spectroscopic studies of the active site ionizations in the enzyme trypsin (EC 3.4.21.4) could arise if a slow pH-dependent conformational change affected the rates at low pH. No such effect is observed within the time range of 1 min- 3 h when pre-incubation of trypsin at pH 2.0 or at pH 6.9 precedes the enzymatic hydrolysis of Nalpha-carbobenzoxy-L-lysine-p-nitrophenyl ester. The deacylation rate of this hydrolysis depends on a single pKa on the enzyme between pH 3 and pH 7.", "contents": "The effect of pre-incubation on trypsin kinetics at low pH. A possible source of discrepancy between kinetic and spectroscopic studies of the active site ionizations in the enzyme trypsin (EC 3.4.21.4) could arise if a slow pH-dependent conformational change affected the rates at low pH. No such effect is observed within the time range of 1 min- 3 h when pre-incubation of trypsin at pH 2.0 or at pH 6.9 precedes the enzymatic hydrolysis of Nalpha-carbobenzoxy-L-lysine-p-nitrophenyl ester. The deacylation rate of this hydrolysis depends on a single pKa on the enzyme between pH 3 and pH 7."}
{"id": "PMID:15616", "title": "Physicochemical properties of alpha- and beta-fibrinogenases of Trimeresurus mucrosquamatus venom.", "content": "alpha- and beta-Fibrinogenases (EC 3.4.21.5) were purified from Trimeresurus mucrosquamatus venom by the technique of recycling chromatography. Both enzymes were single polypeptide chains and homogeneous as judged by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and ultracentrifugation. The sedimentation constants of alpha- and beta-fibrinogenases were 2.52 and 3.04 respectively. The molecular weight of alpha-fibrinogenase was 21 500--23 400, and that of beta-fibrinogenase was 25 000--26 000. The contents of proline, glycine and tryptophan were higher in beta-fibrinogenase than in alpha-fibrinogenase. The isoelectric points of alpha- and beta-fibrinogenases were pH 8.1 and 5.7 respectively. The optimal pH of alpha-fibrinogenase was about 7.4 and that of beta-fibrinogenase was around 8.5. The activity of alpha-fibrinogenase was completely destroyed after 30 min at 60 degrees C, pH 5.6, 7.4 and 9.0, while that of beta-fibrinogenase was not significantly affected by the same treatment. Both enzymes showed proteolytic activities toward fibrinogen and casein, but were devoid of phospholipase A, alkaline phosphomonoesterase and phosphodiesterase activities of the crude venom. The tosyl-L-arginine methylester esterase activity of beta-fibrinogenase was about 17 times that of the crude venom, while alpha-fibrinogenase was completely devoid of this activity. The fibrinogenolytic activity of alpha-fibrinogenase was markedly inhibited by EDTA and cysteine, while that of beta-fibrinogenase was inhibited markedly by phenylmethane sulfonylfluoride and slightly by tosyl-L-lysine chloromethylketone and cysteine.", "contents": "Physicochemical properties of alpha- and beta-fibrinogenases of Trimeresurus mucrosquamatus venom. alpha- and beta-Fibrinogenases (EC 3.4.21.5) were purified from Trimeresurus mucrosquamatus venom by the technique of recycling chromatography. Both enzymes were single polypeptide chains and homogeneous as judged by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and ultracentrifugation. The sedimentation constants of alpha- and beta-fibrinogenases were 2.52 and 3.04 respectively. The molecular weight of alpha-fibrinogenase was 21 500--23 400, and that of beta-fibrinogenase was 25 000--26 000. The contents of proline, glycine and tryptophan were higher in beta-fibrinogenase than in alpha-fibrinogenase. The isoelectric points of alpha- and beta-fibrinogenases were pH 8.1 and 5.7 respectively. The optimal pH of alpha-fibrinogenase was about 7.4 and that of beta-fibrinogenase was around 8.5. The activity of alpha-fibrinogenase was completely destroyed after 30 min at 60 degrees C, pH 5.6, 7.4 and 9.0, while that of beta-fibrinogenase was not significantly affected by the same treatment. Both enzymes showed proteolytic activities toward fibrinogen and casein, but were devoid of phospholipase A, alkaline phosphomonoesterase and phosphodiesterase activities of the crude venom. The tosyl-L-arginine methylester esterase activity of beta-fibrinogenase was about 17 times that of the crude venom, while alpha-fibrinogenase was completely devoid of this activity. The fibrinogenolytic activity of alpha-fibrinogenase was markedly inhibited by EDTA and cysteine, while that of beta-fibrinogenase was inhibited markedly by phenylmethane sulfonylfluoride and slightly by tosyl-L-lysine chloromethylketone and cysteine."}
{"id": "PMID:15617", "title": "Application of trinitrophenylation for the measurement of alpha-amino residues resulting from peptic digestion.", "content": "A sensitive and precise method for the measurement of peptic activity on protein substrate is described. alpha-Amino residues formed by pepsin digestion are photometrically measured by comparing the absorbances of digested and nondigested material which has been trinitrophenylated. The usual problem of high reagent-blank absorbance is eliminated by using an anion exchange resin, Dowex 1-X8. In contrast to Anson's method, the procedure requires only 1/100 the quantity of protein substrate for analysis. It was proved to be particularly useful for the estimation of initial rates of proteolysis.", "contents": "Application of trinitrophenylation for the measurement of alpha-amino residues resulting from peptic digestion. A sensitive and precise method for the measurement of peptic activity on protein substrate is described. alpha-Amino residues formed by pepsin digestion are photometrically measured by comparing the absorbances of digested and nondigested material which has been trinitrophenylated. The usual problem of high reagent-blank absorbance is eliminated by using an anion exchange resin, Dowex 1-X8. In contrast to Anson's method, the procedure requires only 1/100 the quantity of protein substrate for analysis. It was proved to be particularly useful for the estimation of initial rates of proteolysis."}
{"id": "PMID:15618", "title": "Characterization of an adenylyl cyclase activity in particulate preparations from epimastigote forms of Trypanosoma cruzi.", "content": "Particulate preparations from epimastigote forms of Trypanosoma cruzi contain an adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) which could be stored at --20 degree C and resisted 5 cycles of freezing and thawing over 10 days without significant loss of activity. The enzyme reaction strictly required Mn2+, had a pH optimum of 7.7 and was not inhibited or stimulated by NaF. Particles prepared in the presence of 10 mM Mn2+ or Mg2+ were 3--4 times more active than particles prepared in the absence of these cations. However, Mg2+ could not substitute for Mn2+ during enzyme assay nor did it enhance activity in the presence of saturating concentrations of Mn2+. The binary complex Mn - ATP2- was shown to be the true substrate for the adenylyl cyclase and free ATP was highly inhibitory. Plots of enzyme activity against equimolar concentrations of ATP - Mn gave sigmoid curves with n values in Hill plots ranging between 1.5 and 2.0. Excess Mn2+ activated the cyclase catalyzed reaction at low but not at high concentrations of ATP - Mn. In the presence of an excess of 1 mM Mn2+, which transforms 97% of the added ATP to productive Mn - ATP2- complex, the substrate saturation curve assumed a Michaelian pattern with an apparent Km =0.2 mM.", "contents": "Characterization of an adenylyl cyclase activity in particulate preparations from epimastigote forms of Trypanosoma cruzi. Particulate preparations from epimastigote forms of Trypanosoma cruzi contain an adenylyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) which could be stored at --20 degree C and resisted 5 cycles of freezing and thawing over 10 days without significant loss of activity. The enzyme reaction strictly required Mn2+, had a pH optimum of 7.7 and was not inhibited or stimulated by NaF. Particles prepared in the presence of 10 mM Mn2+ or Mg2+ were 3--4 times more active than particles prepared in the absence of these cations. However, Mg2+ could not substitute for Mn2+ during enzyme assay nor did it enhance activity in the presence of saturating concentrations of Mn2+. The binary complex Mn - ATP2- was shown to be the true substrate for the adenylyl cyclase and free ATP was highly inhibitory. Plots of enzyme activity against equimolar concentrations of ATP - Mn gave sigmoid curves with n values in Hill plots ranging between 1.5 and 2.0. Excess Mn2+ activated the cyclase catalyzed reaction at low but not at high concentrations of ATP - Mn. In the presence of an excess of 1 mM Mn2+, which transforms 97% of the added ATP to productive Mn - ATP2- complex, the substrate saturation curve assumed a Michaelian pattern with an apparent Km =0.2 mM."}
{"id": "PMID:15619", "title": "Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations.", "content": "Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine-or taurine-conjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probable attributable to their bile salt contaminants.", "contents": "Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations. Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine-or taurine-conjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probable attributable to their bile salt contaminants."}
{"id": "PMID:15621", "title": "[Activities of pulmonary phospholipases of fetal rats. Variations during development].", "content": "Turnover of adult rat lung phospholipids implies intervention of phospholipases. This work clearly demonstrates: There is in fetal or adult rat lung an inactive form of phospholipase that is convertible to an active form by the action of lysed platelets. An increase of both active and inactive forms of the fetal enzyme with gestational age. The fact that an important part of these activities, at the time of birth, are in the inactive form implies a control mechanism affecting levels of each form of lung phospholipases. These data are discussed in relation to the possible role of the lung phospholipases in Respiratory Distress Syndrome.", "contents": "[Activities of pulmonary phospholipases of fetal rats. Variations during development]. Turnover of adult rat lung phospholipids implies intervention of phospholipases. This work clearly demonstrates: There is in fetal or adult rat lung an inactive form of phospholipase that is convertible to an active form by the action of lysed platelets. An increase of both active and inactive forms of the fetal enzyme with gestational age. The fact that an important part of these activities, at the time of birth, are in the inactive form implies a control mechanism affecting levels of each form of lung phospholipases. These data are discussed in relation to the possible role of the lung phospholipases in Respiratory Distress Syndrome."}
{"id": "PMID:15622", "title": "Fatty acid synthetase complex from the insect Ceratitis capitata.", "content": "Fatty acid synthesis capacity of the insect Ceratitis capitata has been investigated in vitro from [1-14C]acetyl-CoA using homogenates at different stages of development. A maximum activity was observed after 5--6 days of larval development. But homogenates of the pharate adult insect did not show synthetic capacity of fatty acids. Fatty acid synthetase complex has been isolated from the particle-free supernatant fraction of homogenates from the 6-day C. capitata larvae. The enzyme complex was purified 182-fold with respect to the protein contained in the crude extract. The complex was homogeneous when analysed by gel filtration and by polyacrylamide-gel electrophoresis. The molecular weight was 5.2X10(5). The enzyme was dissociated into half-molecular subunits. Amino acid analysis, general properties, stability and kinetic constants (V and Km) for the substrates are reported. The fatty acid synthetase complex from the insect contains 42+/-1-SH residues and one phosphopatetheine moiety per 5.2X10(5). Activity was dependent on the presence of NADPH; FMN strongly inhibited the enzyme activity promoted by NADPH. The enzyme complex synthesized a range of fatty acid (10:0--18:0), palmitate being the predominant end product. The proportions of fatty acids synthesized varied with substrate concentrations. Fatty acids released from the complex were almost completely in the free form.", "contents": "Fatty acid synthetase complex from the insect Ceratitis capitata. Fatty acid synthesis capacity of the insect Ceratitis capitata has been investigated in vitro from [1-14C]acetyl-CoA using homogenates at different stages of development. A maximum activity was observed after 5--6 days of larval development. But homogenates of the pharate adult insect did not show synthetic capacity of fatty acids. Fatty acid synthetase complex has been isolated from the particle-free supernatant fraction of homogenates from the 6-day C. capitata larvae. The enzyme complex was purified 182-fold with respect to the protein contained in the crude extract. The complex was homogeneous when analysed by gel filtration and by polyacrylamide-gel electrophoresis. The molecular weight was 5.2X10(5). The enzyme was dissociated into half-molecular subunits. Amino acid analysis, general properties, stability and kinetic constants (V and Km) for the substrates are reported. The fatty acid synthetase complex from the insect contains 42+/-1-SH residues and one phosphopatetheine moiety per 5.2X10(5). Activity was dependent on the presence of NADPH; FMN strongly inhibited the enzyme activity promoted by NADPH. The enzyme complex synthesized a range of fatty acid (10:0--18:0), palmitate being the predominant end product. The proportions of fatty acids synthesized varied with substrate concentrations. Fatty acids released from the complex were almost completely in the free form."}
{"id": "PMID:15623", "title": "A proton magnetic relaxation study of ferric myoglobin and haemoglobin in water/ethanediol solutions.", "content": "Structural alterations of the haem vicinity of the high-spin derivatives of bovine ferric myoglobin (metmyoglobin) and human haemoglobin and the changes of the interaction with inositol hexaphosphate induced by ethanediol were monitored by solvent-proton magnetic relaxation. On addition of ethanediol up to 60% the fluoromet derivatives exhibit a gradual increase in the accessibility of the haem for the molecules from the solvent. In aquomethaemoglobin solutions with more than 25% ethanediol there is no unique explanation of proton magnetic relaxation. Ethanediol enhances the  binding of inositol hexaphosphate to methaemoglobin, but the structural consequences of this binding on the haem-pockets seem to be diminished. The mechanisms of the observed structural and functional alterations of myoglobin as well as haemoglobin tetramer are discussed here.", "contents": "A proton magnetic relaxation study of ferric myoglobin and haemoglobin in water/ethanediol solutions. Structural alterations of the haem vicinity of the high-spin derivatives of bovine ferric myoglobin (metmyoglobin) and human haemoglobin and the changes of the interaction with inositol hexaphosphate induced by ethanediol were monitored by solvent-proton magnetic relaxation. On addition of ethanediol up to 60% the fluoromet derivatives exhibit a gradual increase in the accessibility of the haem for the molecules from the solvent. In aquomethaemoglobin solutions with more than 25% ethanediol there is no unique explanation of proton magnetic relaxation. Ethanediol enhances the  binding of inositol hexaphosphate to methaemoglobin, but the structural consequences of this binding on the haem-pockets seem to be diminished. The mechanisms of the observed structural and functional alterations of myoglobin as well as haemoglobin tetramer are discussed here."}
{"id": "PMID:15624", "title": "Structural studies by proton magnetic relaxation of stereochemical probes. II. Allosteric effects in human methaemoglobin.", "content": "The haem-iron accessibility to solvent molecules in human aquomet- and fluoromethaemoglobin was studied by the magnetic relaxation of protons from a stereochemical probe (methanol in deuterated solutions) in its dependence on allosteric effects induced by inositol hexaphosphate and pH between 5.5 and 8.5. The exchange of methanol with  bulk solvent was observed only when inositol hexaphosphate was bound to aquomethaemoglobin, which is consistent with a widening of the haemcrevice compared to the conformation in the absence of inositol hexaphosphate. An increase in alkalinity in the physiological range of the Bohr effect results in  a gradual impedence of the solvent dynamics inside the haem-pocket. The fast-relaxation phase of methyl protons indicates that a large number of methanol molecules are under the strong influence of the protein; this effect is considerably smaller with inositol hexaphosphate bound to aquomethaemoglobin. The hypothesis which implies a proton from the coordinated water molecule is responsible for the observed relaxation rates has been critically discussed. The model with a water molecule exchanging between a position next to the sixth-ligand site of the haem-iron and the bulk solvent is further substantiated experimentally. This model has been found to be the simplest and most self consistent in the interpretation of all these proton magnetic relaxation data.", "contents": "Structural studies by proton magnetic relaxation of stereochemical probes. II. Allosteric effects in human methaemoglobin. The haem-iron accessibility to solvent molecules in human aquomet- and fluoromethaemoglobin was studied by the magnetic relaxation of protons from a stereochemical probe (methanol in deuterated solutions) in its dependence on allosteric effects induced by inositol hexaphosphate and pH between 5.5 and 8.5. The exchange of methanol with  bulk solvent was observed only when inositol hexaphosphate was bound to aquomethaemoglobin, which is consistent with a widening of the haemcrevice compared to the conformation in the absence of inositol hexaphosphate. An increase in alkalinity in the physiological range of the Bohr effect results in  a gradual impedence of the solvent dynamics inside the haem-pocket. The fast-relaxation phase of methyl protons indicates that a large number of methanol molecules are under the strong influence of the protein; this effect is considerably smaller with inositol hexaphosphate bound to aquomethaemoglobin. The hypothesis which implies a proton from the coordinated water molecule is responsible for the observed relaxation rates has been critically discussed. The model with a water molecule exchanging between a position next to the sixth-ligand site of the haem-iron and the bulk solvent is further substantiated experimentally. This model has been found to be the simplest and most self consistent in the interpretation of all these proton magnetic relaxation data."}
{"id": "PMID:15625", "title": "Extracellular agglutination factor of myxamoebae produced by Dictyostelium discoideum NC-4.", "content": "A non-dyalyzable specific agglutination factor of myxamoebae obtained from culture broth during the growth phase of Dictyostelium discoideum NC-4 was thermostable but the agglutination activity disappeared below pH 5.0. In the case of formalinized myxamoebae, digestion of the factor with Pronase decreased the activity, but periodate treatment of the factor did not affect the activity. Myxamoebal agglutination by this factor was inhibited by the addition of uronic acid, polyuronide (protuberic acid), and cell-surface polysaccharide prepared from the myxamoebae, but the agglutination was not affected by citric acid or glycine. The factor was purified by ethanol precipitation, column chromatography using DEAE-cellulose and Sepharose-2B, and zone electrophoresis. Chemical analysis of the purified factor gave 61.0% carbohydrate and 26.1% protein, and glucose, mannose, xylose and rhamnose (molar ratios of 9,3 : 3.2 : 2.1 : 1.0) were detected as the component sugars. The content of uronic acid was 12.9%. When the myxamoebae of the growth phase were starved in Millipore-supporting medium, the agglutination activity was detected in the supernatant of the medium.", "contents": "Extracellular agglutination factor of myxamoebae produced by Dictyostelium discoideum NC-4. A non-dyalyzable specific agglutination factor of myxamoebae obtained from culture broth during the growth phase of Dictyostelium discoideum NC-4 was thermostable but the agglutination activity disappeared below pH 5.0. In the case of formalinized myxamoebae, digestion of the factor with Pronase decreased the activity, but periodate treatment of the factor did not affect the activity. Myxamoebal agglutination by this factor was inhibited by the addition of uronic acid, polyuronide (protuberic acid), and cell-surface polysaccharide prepared from the myxamoebae, but the agglutination was not affected by citric acid or glycine. The factor was purified by ethanol precipitation, column chromatography using DEAE-cellulose and Sepharose-2B, and zone electrophoresis. Chemical analysis of the purified factor gave 61.0% carbohydrate and 26.1% protein, and glucose, mannose, xylose and rhamnose (molar ratios of 9,3 : 3.2 : 2.1 : 1.0) were detected as the component sugars. The content of uronic acid was 12.9%. When the myxamoebae of the growth phase were starved in Millipore-supporting medium, the agglutination activity was detected in the supernatant of the medium."}
{"id": "PMID:15626", "title": "Modulation of protein phosphorylation by a factor purified from adipocytes.", "content": "1. A factor which modulates the activity of cyclic AMP-dependent protein kinase copurifies from rat adipocytes with an inhibitor of adenylate cyclase. Purification and stability studies suggest that both effects reside in a single factor previously referred to as a feedback regulator. 2. The magnitude and direction of the feedback regulator effect on cyclic AMP-dependent protein kinase activity was dependent on the concentration of feedback regulator and the concentration and type of protein substrate. Using histone type IIA as substrate, feedback regulator was inhibitory at low histone concentrations and stimulatory at high concentrations. Preincubation of protein kinase with feedback regulator resulted in inhibition at all histone concentrations. With some protein substrates, e.g. histone f2b and casein, inhibition was observed at all histone concentrations. 3. The stimulation of histone type IIA phosphorylation resulted from an increased V with no effect on either the apparent Ka for cyclic AMP or the Km for ATP. Time course studies suggest that feedback regulator increased the rate of phosphorylation without increasing the total number of phosphorylation sites. Increased histone phosphorylation was observed regardless of whether the cyclic AMP-dependent protein kinase was peak I or peak II (off Deae-cellulose), isolated from bovine or rabbit skeletal muscle or rat heart. A small stimulation was observed using cyclic GMP-dependent protein kinase. 4. These results indicate that feedback regulator can inhibit or stimulate protein kinase, an effect which is probably substrate directed, and depends on the reaction conditions. Whether feedback regulator modulated protein phosphorylation in vivo in addition to its inhibition of adenylate cyclase is unknown. However, stimulation of protein kinase activity in the presence of cyclic AMP is a valuable and rapid assay for monitoring feedback regulator fractions during purification procedures.", "contents": "Modulation of protein phosphorylation by a factor purified from adipocytes. 1. A factor which modulates the activity of cyclic AMP-dependent protein kinase copurifies from rat adipocytes with an inhibitor of adenylate cyclase. Purification and stability studies suggest that both effects reside in a single factor previously referred to as a feedback regulator. 2. The magnitude and direction of the feedback regulator effect on cyclic AMP-dependent protein kinase activity was dependent on the concentration of feedback regulator and the concentration and type of protein substrate. Using histone type IIA as substrate, feedback regulator was inhibitory at low histone concentrations and stimulatory at high concentrations. Preincubation of protein kinase with feedback regulator resulted in inhibition at all histone concentrations. With some protein substrates, e.g. histone f2b and casein, inhibition was observed at all histone concentrations. 3. The stimulation of histone type IIA phosphorylation resulted from an increased V with no effect on either the apparent Ka for cyclic AMP or the Km for ATP. Time course studies suggest that feedback regulator increased the rate of phosphorylation without increasing the total number of phosphorylation sites. Increased histone phosphorylation was observed regardless of whether the cyclic AMP-dependent protein kinase was peak I or peak II (off Deae-cellulose), isolated from bovine or rabbit skeletal muscle or rat heart. A small stimulation was observed using cyclic GMP-dependent protein kinase. 4. These results indicate that feedback regulator can inhibit or stimulate protein kinase, an effect which is probably substrate directed, and depends on the reaction conditions. Whether feedback regulator modulated protein phosphorylation in vivo in addition to its inhibition of adenylate cyclase is unknown. However, stimulation of protein kinase activity in the presence of cyclic AMP is a valuable and rapid assay for monitoring feedback regulator fractions during purification procedures."}
{"id": "PMID:15627", "title": "Selective reactions of nucleobases under biological conditions.", "content": "Pentacyanonitrosylferrate/II/ complex reacts under biological conditions (pH= 7.5, T= 25-40 degrees C, dilute solution) selectively with nucleobases. The reaction with adenine and guanine probably leads to nitrosation. A new compound formed in the reaction with adenine is prepared; both this compound and the pentacyanonitrosylferrate/II/ inhibits the multiplication of Escherichia coli.", "contents": "Selective reactions of nucleobases under biological conditions. Pentacyanonitrosylferrate/II/ complex reacts under biological conditions (pH= 7.5, T= 25-40 degrees C, dilute solution) selectively with nucleobases. The reaction with adenine and guanine probably leads to nitrosation. A new compound formed in the reaction with adenine is prepared; both this compound and the pentacyanonitrosylferrate/II/ inhibits the multiplication of Escherichia coli."}
{"id": "PMID:15628", "title": "Oxidation of procarbazine in the presence of Ti(IV).", "content": "The air oxidation of procarbazine in the presence of Ti(IV) was examined as a model system for the effects titanium has on oxidative processes and intermediates involving molecular oxygen. It was found that Ti(IV) inhibited oxidation when the substrate, procarbazine, was coordinated to titanium. This inhibition was most prominent (reduction of overall rate constant by a factor of 10(2)) in its interference with Cu(II) catalyzed oxidation of the substrate whole oxidation by the neutral species O2 was only slightly inhibited (factor of 2). However, when Mn(II) was used to catalyze the oxidation of procarbazine by air, titanium enhanced the catalytic effect of Mn(II) by a factor of 10(2). This enhancement was found to be due to Ti(IV) catalysis of the air oxidation of Mn(II), and the effect was found to be inhibited by catalase but not superoxide dismutase or peroxidase. These results are discussed in terms of a Ti(IV) ability to activate molecular oxygen and its ability to form oxygen free-radical complexes.", "contents": "Oxidation of procarbazine in the presence of Ti(IV). The air oxidation of procarbazine in the presence of Ti(IV) was examined as a model system for the effects titanium has on oxidative processes and intermediates involving molecular oxygen. It was found that Ti(IV) inhibited oxidation when the substrate, procarbazine, was coordinated to titanium. This inhibition was most prominent (reduction of overall rate constant by a factor of 10(2)) in its interference with Cu(II) catalyzed oxidation of the substrate whole oxidation by the neutral species O2 was only slightly inhibited (factor of 2). However, when Mn(II) was used to catalyze the oxidation of procarbazine by air, titanium enhanced the catalytic effect of Mn(II) by a factor of 10(2). This enhancement was found to be due to Ti(IV) catalysis of the air oxidation of Mn(II), and the effect was found to be inhibited by catalase but not superoxide dismutase or peroxidase. These results are discussed in terms of a Ti(IV) ability to activate molecular oxygen and its ability to form oxygen free-radical complexes."}
{"id": "PMID:15629", "title": "Tungsten vs. Molybdenum in models for biological systems.", "content": "Biological systems show a marked preference for molybdenum over tungsten. Studies with methyliminodiacetic acid and L-cysteine have shown that the formation constants of the complexes with Mo(Vi) and W(VI) are very similar. These results imply that these elements would be bound with roughly equal strengths to an apoenzyme or a carrier whether or not these proteins contain a ligating sulfhydryl group. Similarly, transport across a membrane would not be expected to distinguish compounds of these metals providing they are carried in the same oxidation states. However, molybdenum could be distinguished from tungsten through the greater ease of reduction of the compounds of molybdenum.", "contents": "Tungsten vs. Molybdenum in models for biological systems. Biological systems show a marked preference for molybdenum over tungsten. Studies with methyliminodiacetic acid and L-cysteine have shown that the formation constants of the complexes with Mo(Vi) and W(VI) are very similar. These results imply that these elements would be bound with roughly equal strengths to an apoenzyme or a carrier whether or not these proteins contain a ligating sulfhydryl group. Similarly, transport across a membrane would not be expected to distinguish compounds of these metals providing they are carried in the same oxidation states. However, molybdenum could be distinguished from tungsten through the greater ease of reduction of the compounds of molybdenum."}
{"id": "PMID:15631", "title": "[Characterization and separation of exocellular gamma-D-glutamyl-(L)meso-diaminopimelate endopeptidase and LD-carboxypeptidase from Bacillus sphaericus 9602].", "content": "Two exocellular enzymes have been characterized in the culture media of sporulating Bacillus sphaericus 9602 : a gamma-D-glutamyl-(L) meso-diaminopimelate endopeptidase and a L-lysyl-D-alanine carboxypeptidase. These two enzymes and the corresponding membrane-bound peptidases found in Bacillus sphaericus and Bacillus subtilis strains have similar activities. Their separation is described. Both enzymes were precipitated between 25 and 65 per cent (NH4)2SO4 saturation and a first chromatography was carried out on a column of DEAE-cellulose. The separation was performed by chromatography on hydroxyapatite, each enzyme was finally filtered through Ultrogel AcA 34. After separation, the endopeptidase activity and the carboxypeptidase activity increased respectively 93 and 11 fold. Both enzymes have a molecular weight near 200 000. By gel electrophoresis at pH 8.5, they were shown to have different mobilities : the carboxypeptidase is more anionic than the endopeptidase.", "contents": "[Characterization and separation of exocellular gamma-D-glutamyl-(L)meso-diaminopimelate endopeptidase and LD-carboxypeptidase from Bacillus sphaericus 9602]. Two exocellular enzymes have been characterized in the culture media of sporulating Bacillus sphaericus 9602 : a gamma-D-glutamyl-(L) meso-diaminopimelate endopeptidase and a L-lysyl-D-alanine carboxypeptidase. These two enzymes and the corresponding membrane-bound peptidases found in Bacillus sphaericus and Bacillus subtilis strains have similar activities. Their separation is described. Both enzymes were precipitated between 25 and 65 per cent (NH4)2SO4 saturation and a first chromatography was carried out on a column of DEAE-cellulose. The separation was performed by chromatography on hydroxyapatite, each enzyme was finally filtered through Ultrogel AcA 34. After separation, the endopeptidase activity and the carboxypeptidase activity increased respectively 93 and 11 fold. Both enzymes have a molecular weight near 200 000. By gel electrophoresis at pH 8.5, they were shown to have different mobilities : the carboxypeptidase is more anionic than the endopeptidase."}
{"id": "PMID:15632", "title": "[Catalytic properties of a neutral alpha-glucosidase from human kidney].", "content": "The catalytic properties of a neutral alpha-glucosidase purified to homogeneity from human renal cortex are described. The pH optimum was 6 (maltose and starch). It has a broad range of substrate specificity, hydrolysing di- and oligosaccharides with alpha (1 leads to 2), alpha (1 leads to 3), alpha (1 leads to 4) and alpha (1 leads to 6) linkages. Glucosidase action on maltosaccharides was associated with pronounced substrate inhibition at concentrations exceeding 0,5 mM. It also hydrolyses polysaccharides as starch and glycogen. The Km and Vmax values for the various substrates were determined. The enzymes exhibited intrinsic transglucosylase activity. It catalysed glucosyl-transfer reaction from maltose to itself (disproportionation). Mixed substrate inhibition studies, inhibition studies and heat inactivation are interpreted in terms of the existence of at least two interacting sites on the enzyme.", "contents": "[Catalytic properties of a neutral alpha-glucosidase from human kidney]. The catalytic properties of a neutral alpha-glucosidase purified to homogeneity from human renal cortex are described. The pH optimum was 6 (maltose and starch). It has a broad range of substrate specificity, hydrolysing di- and oligosaccharides with alpha (1 leads to 2), alpha (1 leads to 3), alpha (1 leads to 4) and alpha (1 leads to 6) linkages. Glucosidase action on maltosaccharides was associated with pronounced substrate inhibition at concentrations exceeding 0,5 mM. It also hydrolyses polysaccharides as starch and glycogen. The Km and Vmax values for the various substrates were determined. The enzymes exhibited intrinsic transglucosylase activity. It catalysed glucosyl-transfer reaction from maltose to itself (disproportionation). Mixed substrate inhibition studies, inhibition studies and heat inactivation are interpreted in terms of the existence of at least two interacting sites on the enzyme."}
{"id": "PMID:15633", "title": "Structural glycoprotein from the media of pig aorta. Aggregation of the S-carboxamidomethyl subunits.", "content": "Media of pig aorta was extracted with 1 M NaCl and 2 M MgCl2 to remove most of the soluble collagen, proteoglycans and glycoproteins. The glycoproteins remaining in the residue were extracted with 6 M urea-0.1 M mercaptoethanol. The urea soluble proteins were precipitated by dialysis, redissolved in 4 M guanidine-0.05 M DTT and were S-carboxamidomethylated (CM-guanidine extract). This extract was further fractionated by a variety of methods in order to separate a glycoprotein from collagen and proteoglycans. Caesium chloride density-gradient ultracentrifugation of the CM-guanidine extract separated a minor proteoglycan peak from a major glycoprotein fraction still containing some hydroxyproline. This major glycoprotein fraction was excluded as a single peak from Sephadex G 100 and G 200 in 4 M guanidinium chloride or in 6 M urea-0.2 per cent SDS. Sodium dodecylsulphate gel electrophoresis separated this high molecular weight Sephadex fraction into a major low molecular weight (approximately 35000 daltons) component and a minor high molecular weight component. This glycoprotein fraction could also be separated from a collagenous fraction and from proteoglycans by ion exchange chromatography on DEAE cellulose or by gelfiltration on Sepharose 4 B in 6 M urea-0.02 M EDTA-0.2 per cent SDS at pH 7.0. The isolated glycoprotein fraction is rich in dicarboxylic amino acids, contains galactose, mannose, (glucose), N-acetylglucosamine and sialic acid. The S-carboxamidomethyl glycoprotein preparation interacts with acid soluble calf skin collagen on isoelectric focusing in sucrose gradient in urea. This interaction is in favour of the biological role claimed for structural glycoproteins during fibrogenesis and differentiation.", "contents": "Structural glycoprotein from the media of pig aorta. Aggregation of the S-carboxamidomethyl subunits. Media of pig aorta was extracted with 1 M NaCl and 2 M MgCl2 to remove most of the soluble collagen, proteoglycans and glycoproteins. The glycoproteins remaining in the residue were extracted with 6 M urea-0.1 M mercaptoethanol. The urea soluble proteins were precipitated by dialysis, redissolved in 4 M guanidine-0.05 M DTT and were S-carboxamidomethylated (CM-guanidine extract). This extract was further fractionated by a variety of methods in order to separate a glycoprotein from collagen and proteoglycans. Caesium chloride density-gradient ultracentrifugation of the CM-guanidine extract separated a minor proteoglycan peak from a major glycoprotein fraction still containing some hydroxyproline. This major glycoprotein fraction was excluded as a single peak from Sephadex G 100 and G 200 in 4 M guanidinium chloride or in 6 M urea-0.2 per cent SDS. Sodium dodecylsulphate gel electrophoresis separated this high molecular weight Sephadex fraction into a major low molecular weight (approximately 35000 daltons) component and a minor high molecular weight component. This glycoprotein fraction could also be separated from a collagenous fraction and from proteoglycans by ion exchange chromatography on DEAE cellulose or by gelfiltration on Sepharose 4 B in 6 M urea-0.02 M EDTA-0.2 per cent SDS at pH 7.0. The isolated glycoprotein fraction is rich in dicarboxylic amino acids, contains galactose, mannose, (glucose), N-acetylglucosamine and sialic acid. The S-carboxamidomethyl glycoprotein preparation interacts with acid soluble calf skin collagen on isoelectric focusing in sucrose gradient in urea. This interaction is in favour of the biological role claimed for structural glycoproteins during fibrogenesis and differentiation."}
{"id": "PMID:15634", "title": "Interaction between photoperiod, temperature, and chilling in dormant larvae of the tree-hole mosquito, Toxorhynchites rutilus Coq.", "content": "1. Unchilled, diapausing larvae of Toxorhynchites rutilus rely on photoperiod for the maintenance of diapause. The photoperiodic clock is temperature-compensated between 16.5 degrees and 25 degrees C, maintaining both a similar set-joint and inherent accuracy over this range. The rates of development among larvae terminating diapause are dependent upon both temperature and photoperiod. 2. Chilling of dormant Toxorhynchites rutilus can promote response to progressively shorter daylengths, thus decreasing the critical photoperiod. Chilling can also accelerate response to long days, thereby decreasing the depth of diapause and, after prolonged exposure, can eventually terminate diapause directly, leaving subsequent morphogenesis independent of photoperiod. 3. The optimal temperature for these effects of chilling is above 4 degrees C, below 16.5 degrees C, and may lie around 7 degrees C. 4. Temperatures between 5 degrees and 15 degrees C are vernal and autumnal rather than hibernal. The interaction between chilling and photoperiod may then represent an adaptive compromise between selection due to long-term climatic trends and the vagaries of spring weather.", "contents": "Interaction between photoperiod, temperature, and chilling in dormant larvae of the tree-hole mosquito, Toxorhynchites rutilus Coq. 1. Unchilled, diapausing larvae of Toxorhynchites rutilus rely on photoperiod for the maintenance of diapause. The photoperiodic clock is temperature-compensated between 16.5 degrees and 25 degrees C, maintaining both a similar set-joint and inherent accuracy over this range. The rates of development among larvae terminating diapause are dependent upon both temperature and photoperiod. 2. Chilling of dormant Toxorhynchites rutilus can promote response to progressively shorter daylengths, thus decreasing the critical photoperiod. Chilling can also accelerate response to long days, thereby decreasing the depth of diapause and, after prolonged exposure, can eventually terminate diapause directly, leaving subsequent morphogenesis independent of photoperiod. 3. The optimal temperature for these effects of chilling is above 4 degrees C, below 16.5 degrees C, and may lie around 7 degrees C. 4. Temperatures between 5 degrees and 15 degrees C are vernal and autumnal rather than hibernal. The interaction between chilling and photoperiod may then represent an adaptive compromise between selection due to long-term climatic trends and the vagaries of spring weather."}
{"id": "PMID:15635", "title": "The ontogeny of swimming behavior in the scyphozoan, Aurelia aurita. I. Electrophysiological analysis.", "content": "1. Electrical correlates of behavioral activity were observed in the lip and tentacles of the polyp, but none were detected during column contraction. The tentacles are the most electrically active tissue, and the potentials are conducted along the length of the tentacle, but conduction to other parts of the animal were not observed. 2. Although the tentacles of the polyp and the rhopalia of the medusa are probably homologous, the development of pacemaker activity during strobilation is not a smooth transition from tentacle contraction potentials (TCPs) to marginal ganglion potentials (MGPs). This result indicates that each pacemaker activity develops de novo. 3. Two types of behavior were observed in the polyp: local responses, and coordinated activity which involved integrated responses in several body parts. The coordinated responses indicate that neurological coordination can take place in the polyp. Furthermore, feeding and spasm in the ephyra are similar to feeding and the protective response in the polyp. This similarity suggests that both coordinated responses in the polyp are coordinated by interneural facilitation in the diffuse nerve net (DNN) as in the ephyra. 4. Swimming in the ephyra is a medusoid behavior but feeding and spasm are coordinated by the DNN and are polypoid responses. Therefore, the ephyra is a mixture of polypoid and medusoid behaviors. As the ephyra matures into an adult medusa both polypoid responses are lost, but the DNN remains to modulate pacemaker output and control marginal tentacle contractions. As development proceeds from polyp, to ephyra, to medusa, each subsequent stage acquires some new behavior while retaining some aspect from the previous stage.", "contents": "The ontogeny of swimming behavior in the scyphozoan, Aurelia aurita. I. Electrophysiological analysis. 1. Electrical correlates of behavioral activity were observed in the lip and tentacles of the polyp, but none were detected during column contraction. The tentacles are the most electrically active tissue, and the potentials are conducted along the length of the tentacle, but conduction to other parts of the animal were not observed. 2. Although the tentacles of the polyp and the rhopalia of the medusa are probably homologous, the development of pacemaker activity during strobilation is not a smooth transition from tentacle contraction potentials (TCPs) to marginal ganglion potentials (MGPs). This result indicates that each pacemaker activity develops de novo. 3. Two types of behavior were observed in the polyp: local responses, and coordinated activity which involved integrated responses in several body parts. The coordinated responses indicate that neurological coordination can take place in the polyp. Furthermore, feeding and spasm in the ephyra are similar to feeding and the protective response in the polyp. This similarity suggests that both coordinated responses in the polyp are coordinated by interneural facilitation in the diffuse nerve net (DNN) as in the ephyra. 4. Swimming in the ephyra is a medusoid behavior but feeding and spasm are coordinated by the DNN and are polypoid responses. Therefore, the ephyra is a mixture of polypoid and medusoid behaviors. As the ephyra matures into an adult medusa both polypoid responses are lost, but the DNN remains to modulate pacemaker output and control marginal tentacle contractions. As development proceeds from polyp, to ephyra, to medusa, each subsequent stage acquires some new behavior while retaining some aspect from the previous stage."}
{"id": "PMID:15636", "title": "The ontogeny of swimming behavior in the scyphozoan, Aurelia aurita. II. The effects of ions and drugs.", "content": "1. The responses of Aurelia medusae to pharmacological agents and ionic variation were classified into four response types: Type I, no response; Type II, inhibition of pacemaker activity; Type III, inhibition of both pacemakers and swimming muscles; and Type IV, increase in pacemaker output. 2. The swimming pacemakers of Aurelia medusae become hyperactive in Mg+2-free solutions (Type IV). This response appears to be general in swimming scyphozoa. 3. The response pattern to pharmacologically-active compounds indicates that the coelenterate neuromuscular system is quite different than those in other phyla. In fact, the response spectrum is not consistent within the Cnidaria. 4. Similarly, the responses of adult medusae to ionic variation show no consistent pattern within various scyphomedusae. 5. Test solutions from each response type established with medusae were selected and tested on the scyphistoma and strobila stages. The comparison of the responses to the test solutions between the medusa, scyphistoma, and strobila showed that the neuromuscular systems are physiologically different. The strobila, specificially the ephyra, is a mixture of both polypoid and medusoid response types. The strobila, therefore, is physiologically an intermediate stage in the development of the adult medusa.", "contents": "The ontogeny of swimming behavior in the scyphozoan, Aurelia aurita. II. The effects of ions and drugs. 1. The responses of Aurelia medusae to pharmacological agents and ionic variation were classified into four response types: Type I, no response; Type II, inhibition of pacemaker activity; Type III, inhibition of both pacemakers and swimming muscles; and Type IV, increase in pacemaker output. 2. The swimming pacemakers of Aurelia medusae become hyperactive in Mg+2-free solutions (Type IV). This response appears to be general in swimming scyphozoa. 3. The response pattern to pharmacologically-active compounds indicates that the coelenterate neuromuscular system is quite different than those in other phyla. In fact, the response spectrum is not consistent within the Cnidaria. 4. Similarly, the responses of adult medusae to ionic variation show no consistent pattern within various scyphomedusae. 5. Test solutions from each response type established with medusae were selected and tested on the scyphistoma and strobila stages. The comparison of the responses to the test solutions between the medusa, scyphistoma, and strobila showed that the neuromuscular systems are physiologically different. The strobila, specificially the ephyra, is a mixture of both polypoid and medusoid response types. The strobila, therefore, is physiologically an intermediate stage in the development of the adult medusa."}
{"id": "PMID:15637", "title": "[Isolation of individual proteases from protofradin].", "content": "An electrophoretically homogeneous trypsin-like proteinase, two homogeneous proteases (presumably metal-containing) and two elastases, possessing the ATEE-esterase activity, were isolated from protofradin, a protease preparation from Actinomyces fradiae 119, using fractionation on KM-cellulose K-32. The trypsin like proteinase of protofradin possesses the esterase activity, equal to the activity of pancreatic trypsin. Protofradin elastases differ in their pH optima, response to EDTA, stability upon storage and the degree of elastin hydrolysis. The specificity of elastase is probably the same, since in elastin both enzymes hydrolyze the peptide bonds, formed by the NH2-group of glycine and alanine residues, found in elastin in large amounts. The end products of elastin hydrolysis are tripeptides.", "contents": "[Isolation of individual proteases from protofradin]. An electrophoretically homogeneous trypsin-like proteinase, two homogeneous proteases (presumably metal-containing) and two elastases, possessing the ATEE-esterase activity, were isolated from protofradin, a protease preparation from Actinomyces fradiae 119, using fractionation on KM-cellulose K-32. The trypsin like proteinase of protofradin possesses the esterase activity, equal to the activity of pancreatic trypsin. Protofradin elastases differ in their pH optima, response to EDTA, stability upon storage and the degree of elastin hydrolysis. The specificity of elastase is probably the same, since in elastin both enzymes hydrolyze the peptide bonds, formed by the NH2-group of glycine and alanine residues, found in elastin in large amounts. The end products of elastin hydrolysis are tripeptides."}
{"id": "PMID:15638", "title": "[Metal proteases from Bac. subtilis].", "content": "Metal and serine proteases were separated on the biospecific sorbent. Two different, homogeneous metal proteases were obtained by rechromatography of the metal protease. Activation energies, heat stability, molecular weights, influence of inhibitors, the dependence of activity on pH and temperature were determined. Properties of two metal proteases were compared with those of literary analogs.", "contents": "[Metal proteases from Bac. subtilis]. Metal and serine proteases were separated on the biospecific sorbent. Two different, homogeneous metal proteases were obtained by rechromatography of the metal protease. Activation energies, heat stability, molecular weights, influence of inhibitors, the dependence of activity on pH and temperature were determined. Properties of two metal proteases were compared with those of literary analogs."}
{"id": "PMID:15639", "title": "[Purification and properties of peroxidase from tea leaves].", "content": "Purification of fractions of tea leaves peroxidase is described. During ion-exchange chromatography on DEAE- and CM-cellulose peroxidase is eluted into six fractions, differing in their electrophoretic properties. The enzyme showed optimal activity at pH 4.1-5.0, when the enzyme fractions of guaiacol adsorbed on DEAE-cellulose were used as a substrate; in case of enzyme fractions adsorbed on CM-cellulose it was observed within pH range of 5.4-6.2. The dependence curves of the initial rate of the reaction on the substrate concentration were S-shaped in case of the latter fractions. Peroxidase is shown to catalyze the oxidation of tea catechins; its activity is inhibited by the products of their condensation. The catalytic effect of the enzyme on the oxidation of phenolic acids, e.g. chlorogenic, caffeic and gallic, was far stronger than on that of tea catechins, pyrogallol and pyrocatechin. It was established that two fractions of the enzyme possess predominantly the phloroglucinol oxidase activity, whereas the other fractions do not catalyze the oxidation of phloroglucin. The molecular weights of some peroxidase fractions estimated by polyacryl amide gel electrophoresis are 26.000+/-1.100, 45.00+/-1.200 and 50.000+/-1.500.", "contents": "[Purification and properties of peroxidase from tea leaves]. Purification of fractions of tea leaves peroxidase is described. During ion-exchange chromatography on DEAE- and CM-cellulose peroxidase is eluted into six fractions, differing in their electrophoretic properties. The enzyme showed optimal activity at pH 4.1-5.0, when the enzyme fractions of guaiacol adsorbed on DEAE-cellulose were used as a substrate; in case of enzyme fractions adsorbed on CM-cellulose it was observed within pH range of 5.4-6.2. The dependence curves of the initial rate of the reaction on the substrate concentration were S-shaped in case of the latter fractions. Peroxidase is shown to catalyze the oxidation of tea catechins; its activity is inhibited by the products of their condensation. The catalytic effect of the enzyme on the oxidation of phenolic acids, e.g. chlorogenic, caffeic and gallic, was far stronger than on that of tea catechins, pyrogallol and pyrocatechin. It was established that two fractions of the enzyme possess predominantly the phloroglucinol oxidase activity, whereas the other fractions do not catalyze the oxidation of phloroglucin. The molecular weights of some peroxidase fractions estimated by polyacryl amide gel electrophoresis are 26.000+/-1.100, 45.00+/-1.200 and 50.000+/-1.500."}
{"id": "PMID:15640", "title": "[Isolation, purification and investigation of physico-chemical properties and specificity of Leu-Gly-Gly-amino peptidase].", "content": "A highly purified (237-fold) preparation of extracellular Leu-Gly-Gly aminopeptidase was isolated from the 716 strain of mould Aspergillis flavus. The enzyme was found electrophoretically and enzymatically homogeneous, using Leu-beta-naphthylimide as substrate. The pH optimum is 8.60; the temperature optimum is about 50 degrees C. The enzyme was inhibited by EDTA and completely reactivated by Co2+ ions; Ca2+ and Mn2+ ions considerably restored the enzyme activity. The enzyme showed the optimal activity during the cleavage of substrates, containing N-terminal leucine. Mild hydrolysis of leucine-free tripeptides and dipeptides with N-terminal glycine and alanine was observed. The enzyme was found to be stereospecific in some respects. Peptides with a blocked terminal NH2-group are not hydrolyzed by the enzyme.", "contents": "[Isolation, purification and investigation of physico-chemical properties and specificity of Leu-Gly-Gly-amino peptidase]. A highly purified (237-fold) preparation of extracellular Leu-Gly-Gly aminopeptidase was isolated from the 716 strain of mould Aspergillis flavus. The enzyme was found electrophoretically and enzymatically homogeneous, using Leu-beta-naphthylimide as substrate. The pH optimum is 8.60; the temperature optimum is about 50 degrees C. The enzyme was inhibited by EDTA and completely reactivated by Co2+ ions; Ca2+ and Mn2+ ions considerably restored the enzyme activity. The enzyme showed the optimal activity during the cleavage of substrates, containing N-terminal leucine. Mild hydrolysis of leucine-free tripeptides and dipeptides with N-terminal glycine and alanine was observed. The enzyme was found to be stereospecific in some respects. Peptides with a blocked terminal NH2-group are not hydrolyzed by the enzyme."}
{"id": "PMID:15641", "title": "[Study of the initial reaction of enzymatic oxidation of 1,8-dimethylnaphthalene].", "content": "Crude enzymatic preparation has been obtained from Pseudomonas bacteria which oxidises 1,8-DMN during 10-hour incubation with the following formation of the same products which are formed when this compound is oxidized by the intact cells. The first product of the oxidation is 1-methyl-8-oxymethylnaphtalene (compound I), obtained as a result of hydroxylation of one methyl group. Probably hydroxylase of 1,8-DMN may be referred to the class of oxigenases of the basis of the absence of 18O incorporation from H218O to compound I, and also resulting from the data on absorption of molecular oxygen during the reaction. The enzyme is completely inhibited by chelating agents of Fe2+ NAD(P)H and Fe2+ stimulates the reaction of 1.8 DMN oxidation.", "contents": "[Study of the initial reaction of enzymatic oxidation of 1,8-dimethylnaphthalene]. Crude enzymatic preparation has been obtained from Pseudomonas bacteria which oxidises 1,8-DMN during 10-hour incubation with the following formation of the same products which are formed when this compound is oxidized by the intact cells. The first product of the oxidation is 1-methyl-8-oxymethylnaphtalene (compound I), obtained as a result of hydroxylation of one methyl group. Probably hydroxylase of 1,8-DMN may be referred to the class of oxigenases of the basis of the absence of 18O incorporation from H218O to compound I, and also resulting from the data on absorption of molecular oxygen during the reaction. The enzyme is completely inhibited by chelating agents of Fe2+ NAD(P)H and Fe2+ stimulates the reaction of 1.8 DMN oxidation."}
{"id": "PMID:15642", "title": "[Purification of hirudin by the method of isoelectric focusing].", "content": "Crude hirudin preparation was purified by isoelectric focussing in pH gradient 3-5. The presence of at least two active isoforms with pI 3.8 and 3.9 was demonstrated. The component with pI value of 3.9 possessed the specific activity as high as 8200 NIH AT units/mg.", "contents": "[Purification of hirudin by the method of isoelectric focusing]. Crude hirudin preparation was purified by isoelectric focussing in pH gradient 3-5. The presence of at least two active isoforms with pI 3.8 and 3.9 was demonstrated. The component with pI value of 3.9 possessed the specific activity as high as 8200 NIH AT units/mg."}
{"id": "PMID:15643", "title": "[Isolation and properties of cortisol inducible and cortisol non-inducible isoenzymes of rat liver tyrosine aminotransferase].", "content": "Rat liver contains two groups of tyrosine aminotransferase (TAT) isoenzymes; during electrophoresis in agar gel one of the groups moves to the anode and the other--to the catode. Cortisol is shown to induce only the anode isoenzymes of TAT, which were isolated, purified and thoroughly analyzed. The inducible anode isoenzyme of TAT spearated from other proteins is more sensitive to the effect of proteases (trypsin and chymotrypsin) than the catode isoenzyme. Some kinetic parameters of the purified TAT isoenzymes were studied. Both isoenzymes have pH optimum around 7.5; their apparent Km values for tyrosine are also similar. However, the catode isoenzyme of TAT possesses a higher affinity for alpha-ketoglutarate than does the anode isoenzyme. Unlike the latter, the former isoenzyme may use oxaloacetate as an amino group acceptor. Pyridoxal phosphate is firmly bound to the catode isoenzyme and can be readily spearated from the anode isoenzyme during dyalisis. An increased sensitivity of the inducible isoenzyme to proteases is due not only to the possibility of coenzyme dissociation, but also to some specific properties of the apoenzyme. The results obtained support the assumption that a high sensitivity of the inducible isoenzymes to proteases provides for a removal of excessive amounts of the enzymes from the cells under cessation of hormonal induction, thus maintaining enzymatic homostasis in the cell.", "contents": "[Isolation and properties of cortisol inducible and cortisol non-inducible isoenzymes of rat liver tyrosine aminotransferase]. Rat liver contains two groups of tyrosine aminotransferase (TAT) isoenzymes; during electrophoresis in agar gel one of the groups moves to the anode and the other--to the catode. Cortisol is shown to induce only the anode isoenzymes of TAT, which were isolated, purified and thoroughly analyzed. The inducible anode isoenzyme of TAT spearated from other proteins is more sensitive to the effect of proteases (trypsin and chymotrypsin) than the catode isoenzyme. Some kinetic parameters of the purified TAT isoenzymes were studied. Both isoenzymes have pH optimum around 7.5; their apparent Km values for tyrosine are also similar. However, the catode isoenzyme of TAT possesses a higher affinity for alpha-ketoglutarate than does the anode isoenzyme. Unlike the latter, the former isoenzyme may use oxaloacetate as an amino group acceptor. Pyridoxal phosphate is firmly bound to the catode isoenzyme and can be readily spearated from the anode isoenzyme during dyalisis. An increased sensitivity of the inducible isoenzyme to proteases is due not only to the possibility of coenzyme dissociation, but also to some specific properties of the apoenzyme. The results obtained support the assumption that a high sensitivity of the inducible isoenzymes to proteases provides for a removal of excessive amounts of the enzymes from the cells under cessation of hormonal induction, thus maintaining enzymatic homostasis in the cell."}
{"id": "PMID:15644", "title": "[The relationship of cottonseed's triacetinase].", "content": "A multiplicity of triacetinase forms in cotton seeds was studied. Three triacetinases (A, B and C) were shown to undergo reciprocal conversions under storage and during some purification procedures (effect of pH, ionic strength, ion-exchange chromatography, concentration, lyophilization, etc.). On the other hand, the presence of different triacetinase forms in cotton seeds cannot be considered an artefact of isolation, since the formation of more active low-molecular forms from inactive high-molecular forms occurs during seed germination. A correlation between the activity and stability of the enzymes on one hand and their quaternary structure on the other, is discussed.", "contents": "[The relationship of cottonseed's triacetinase]. A multiplicity of triacetinase forms in cotton seeds was studied. Three triacetinases (A, B and C) were shown to undergo reciprocal conversions under storage and during some purification procedures (effect of pH, ionic strength, ion-exchange chromatography, concentration, lyophilization, etc.). On the other hand, the presence of different triacetinase forms in cotton seeds cannot be considered an artefact of isolation, since the formation of more active low-molecular forms from inactive high-molecular forms occurs during seed germination. A correlation between the activity and stability of the enzymes on one hand and their quaternary structure on the other, is discussed."}
{"id": "PMID:15645", "title": "[Participation of the iron-containing pterine-protein complex in NADP reduction and electron transport].", "content": "A factor of protein nature, containing pteridines and iron ions was isolated from pea leaves. The compound was shown capable of activating NADP reduction during chloroplasts illumination in the absence of ferredoxin. The compound was termed \"NADP-reducing factor\" (NRP). Freshly isolated NRF in combination with the protein possessing the NADP-reductase activity, reduces NADP in the dark. The factor accepts the electron from the reaction site of the first photosystem and activates hydrogen liberation in the systems, containing hydrogenase. A possibility of an existence of an additional site of NADP reduction in chloroplasts is discussed.", "contents": "[Participation of the iron-containing pterine-protein complex in NADP reduction and electron transport]. A factor of protein nature, containing pteridines and iron ions was isolated from pea leaves. The compound was shown capable of activating NADP reduction during chloroplasts illumination in the absence of ferredoxin. The compound was termed \"NADP-reducing factor\" (NRP). Freshly isolated NRF in combination with the protein possessing the NADP-reductase activity, reduces NADP in the dark. The factor accepts the electron from the reaction site of the first photosystem and activates hydrogen liberation in the systems, containing hydrogenase. A possibility of an existence of an additional site of NADP reduction in chloroplasts is discussed."}
{"id": "PMID:15646", "title": "[Study of splitting dinucleoside monophosphates by Penicillium brevicompactum RNAse].", "content": "In studies of splitting of transferase substrates cytidylyl-(3' leeds to 5')-adenosine and adenylyl-(3'leds to to 5')-cytidine by Penicillium brevicompactum RNAase the pH-optimum activity of enzyme has been found to fall within the range of 4.7 +/- 0;1; temperature optimum--within 41 degrees--43 degrees C; adenine-nucleotides, their constituent components and polyphosphates display the properties of competitive inhibitors on splitting substrates and that amino-acid residues (presumably weakly-  and strongly-protonated imidasole groups) function in the active site of this enzyme (pK 5.88 +/- 0,1 AND 6.6 +/- 0.1). A comparison of some physico-chemical and kinetic parameters of Penicillium breviocompactum RNAse to those of other nonspecific RNAses of fungi is made.", "contents": "[Study of splitting dinucleoside monophosphates by Penicillium brevicompactum RNAse]. In studies of splitting of transferase substrates cytidylyl-(3' leeds to 5')-adenosine and adenylyl-(3'leds to to 5')-cytidine by Penicillium brevicompactum RNAase the pH-optimum activity of enzyme has been found to fall within the range of 4.7 +/- 0;1; temperature optimum--within 41 degrees--43 degrees C; adenine-nucleotides, their constituent components and polyphosphates display the properties of competitive inhibitors on splitting substrates and that amino-acid residues (presumably weakly-  and strongly-protonated imidasole groups) function in the active site of this enzyme (pK 5.88 +/- 0,1 AND 6.6 +/- 0.1). A comparison of some physico-chemical and kinetic parameters of Penicillium breviocompactum RNAse to those of other nonspecific RNAses of fungi is made."}
{"id": "PMID:15647", "title": "[Glutamine metabolism regulation in Chlorella pyrenoidosa. Regulation of Chlorella glutamine synthetase activity by amino acids].", "content": "Effect of glutamine and its metabolites (amino acids) on Chlorella glutamine synthetase (GS) (E.C.6.3.1.2) in the presence of Mg or Mn was studied. Purified GS preparation was used, isolated from Chlorella grown in the presence of NH as a sole nitrogen source. Glutamate, aspartate, alanine and glycine inhibit GS activity in the presence of both Mg and Mn. Tryptophane and valine (up to 15 mM) activate GS in the presence of Mn. Tryptophane inhibits GS in the system with Mg. Sinergistic inhibition was observed under the combined effect of amino acids on GS in the presence of Mn and aspartate or alanine. The change of GS activity observed is supposed to be due to the inhibitory effect of glutamine and amino acids studied, since the glutamine content is increased (in 2.5 times for 5 min) and that of alanine and dicarbonic amino acids (for the following 15 min) under NH assimilation in Chlorella cells.", "contents": "[Glutamine metabolism regulation in Chlorella pyrenoidosa. Regulation of Chlorella glutamine synthetase activity by amino acids]. Effect of glutamine and its metabolites (amino acids) on Chlorella glutamine synthetase (GS) (E.C.6.3.1.2) in the presence of Mg or Mn was studied. Purified GS preparation was used, isolated from Chlorella grown in the presence of NH as a sole nitrogen source. Glutamate, aspartate, alanine and glycine inhibit GS activity in the presence of both Mg and Mn. Tryptophane and valine (up to 15 mM) activate GS in the presence of Mn. Tryptophane inhibits GS in the system with Mg. Sinergistic inhibition was observed under the combined effect of amino acids on GS in the presence of Mn and aspartate or alanine. The change of GS activity observed is supposed to be due to the inhibitory effect of glutamine and amino acids studied, since the glutamine content is increased (in 2.5 times for 5 min) and that of alanine and dicarbonic amino acids (for the following 15 min) under NH assimilation in Chlorella cells."}
{"id": "PMID:15648", "title": "[Electrochemical gradient of H+ ions as an immediate source of energy during bacteria movement].", "content": "An uncoupler of oxidative phosphorylation causes an instantaneous cessation of movement of bacteria Rhodospirillum rubrum in the presence and in the absence of oligomycin. It is concluded that such cessation is not due to a decrease in the ATP concentration but to the elimination of deltamicron-H+ by the uncoupler. The mobility of the bacteria does not practically change in the presence of acetate and is, to some extent, decreased after addition of valinomycin or penetrating cation of tetraphenyl phosphonium. Under a combined action of acetate and valinomycin the movement is depleted. It is concluded that both constituents of deltamicronH+-transmembrane difference of electric potentials and the pH gradient--may serve as energy sources for the bacteria movement. Inhibitory analysis data suggest that the bacteria movement may be maintained by any of the deltamicronH+  sources, e.g. light-dependent cyclic electron transfer, respiration, ATPase and membrane pyrophosphatase.", "contents": "[Electrochemical gradient of H+ ions as an immediate source of energy during bacteria movement]. An uncoupler of oxidative phosphorylation causes an instantaneous cessation of movement of bacteria Rhodospirillum rubrum in the presence and in the absence of oligomycin. It is concluded that such cessation is not due to a decrease in the ATP concentration but to the elimination of deltamicron-H+ by the uncoupler. The mobility of the bacteria does not practically change in the presence of acetate and is, to some extent, decreased after addition of valinomycin or penetrating cation of tetraphenyl phosphonium. Under a combined action of acetate and valinomycin the movement is depleted. It is concluded that both constituents of deltamicronH+-transmembrane difference of electric potentials and the pH gradient--may serve as energy sources for the bacteria movement. Inhibitory analysis data suggest that the bacteria movement may be maintained by any of the deltamicronH+  sources, e.g. light-dependent cyclic electron transfer, respiration, ATPase and membrane pyrophosphatase."}
{"id": "PMID:15649", "title": "[Inhibitory effect platinum and palladium complexes as indicator of conformational changes in sarcoplasmic reticulum membranes].", "content": "Inhibition of Ca2+-dependent ATPase of sarcoplasmic reticulum membranes (SRM) by platinum and palladium complexes is considerable enhanced during the incubation of these compunds with SRM preparations in the presence of small (10(-5) M) concentrations of ATP or ADP. AMP and nucleotides with non-adenine bases do not have inhibitory effect. To increase the sensitivity of Ca2+-dependent ATPase to platinum and palladium complexes under the action of ATP (but not ADP), the presence of free Ca2+-ions in the medium is required. In the absence of ATP Ca2+-ions do not affect the inhibiting effect of the complexes. The increase in pH of the medium up to 8.5 and the increase of temperature up to 45degree C sharply decrease the ATP ability to enchance the sensitivity of Ca2+-dependent  ATPase to platinum and palladium compunds. It is assumed that the ATP ability to enhance  Ca2+-dependent ATPase inhibition by platinum and palladium complexes is due to ATP-dependent structural changes in SRM, which increase the availability of certain groups of the enzyme to those compounds.", "contents": "[Inhibitory effect platinum and palladium complexes as indicator of conformational changes in sarcoplasmic reticulum membranes]. Inhibition of Ca2+-dependent ATPase of sarcoplasmic reticulum membranes (SRM) by platinum and palladium complexes is considerable enhanced during the incubation of these compunds with SRM preparations in the presence of small (10(-5) M) concentrations of ATP or ADP. AMP and nucleotides with non-adenine bases do not have inhibitory effect. To increase the sensitivity of Ca2+-dependent ATPase to platinum and palladium complexes under the action of ATP (but not ADP), the presence of free Ca2+-ions in the medium is required. In the absence of ATP Ca2+-ions do not affect the inhibiting effect of the complexes. The increase in pH of the medium up to 8.5 and the increase of temperature up to 45degree C sharply decrease the ATP ability to enchance the sensitivity of Ca2+-dependent  ATPase to platinum and palladium compunds. It is assumed that the ATP ability to enhance  Ca2+-dependent ATPase inhibition by platinum and palladium complexes is due to ATP-dependent structural changes in SRM, which increase the availability of certain groups of the enzyme to those compounds."}
{"id": "PMID:15650", "title": "[Adenine uptake in Neurospora crassa mycelium].", "content": "The uptake of 8-C14-adenine in N. crassa strain Lindegren (+) was studied. The ability of N. crassa cells to uptake adenine from the medium reaches maximum at the very beginning of the logarithmic stage of growth. Adenine enters the mycelium against the concentration gradient. The uptake of adenine is maximal at 25-30 degrees C, pH 4,6-4,8, and adenine concentration in the medium about 2-15X10(-6) M. The entry of adenine into the cells follows normal Michaelis-Menten kinetics, the apparent Km=0.83+/-0.02 micron. The uptake is inhibited at higher concentrations (10(-3)-10(-4) M) of adenine. 2,6-Diaminopurine, hypoxanthine, guanine, 8-azaadenine and 8-azaguanine inhibit the transport of adenine into the cell. Xanthine and cytosine do not affect the uptake of adenine. Adenine taken up into the cell is rapidly metabolized to AMP, ADP and ATP.", "contents": "[Adenine uptake in Neurospora crassa mycelium]. The uptake of 8-C14-adenine in N. crassa strain Lindegren (+) was studied. The ability of N. crassa cells to uptake adenine from the medium reaches maximum at the very beginning of the logarithmic stage of growth. Adenine enters the mycelium against the concentration gradient. The uptake of adenine is maximal at 25-30 degrees C, pH 4,6-4,8, and adenine concentration in the medium about 2-15X10(-6) M. The entry of adenine into the cells follows normal Michaelis-Menten kinetics, the apparent Km=0.83+/-0.02 micron. The uptake is inhibited at higher concentrations (10(-3)-10(-4) M) of adenine. 2,6-Diaminopurine, hypoxanthine, guanine, 8-azaadenine and 8-azaguanine inhibit the transport of adenine into the cell. Xanthine and cytosine do not affect the uptake of adenine. Adenine taken up into the cell is rapidly metabolized to AMP, ADP and ATP."}
{"id": "PMID:15651", "title": "[beta-Glucosidases from fungus Geotrichum candidum].", "content": "beta-Glucosidases from Geotrichum candidum 3C cellulase preparation were separated from C1 enzymes and beta-1,4-glucanases by means of DEAE-Sephadex A-50 chromatography, gel filtration through P-150 Biogel and chromatography on CM-cellulose, and then were fractionated by isoelectric focusing using carrier ampholites with pH ranges 3-6 and 4-6. beta-Glucosidases with pI 3.8, 4.2, 4.6, 5.1, 5.6 and 6.2 were found in cellulase preparation from G. candidum 3C. Molecular weight of beta-glucosidases with pI 3.8, 4.2, 4.6 and 6.2, isolated under isoelectric focusing, were estimated by means of gel filtration through Sephadex G-200 to be 35000, 123000, 188000 and 223000 respectively. beta-Glucosidases with pI 3.8, 4.6, 5.6 and 6.2 hydrolyzed cellobiose and did not attack p-nitrophenyl-beta-D-glucopyranoside; those with pI 4.2 and 5.6 hydrolyzed p-nitrophenyl-beta-D-glucopyranoside and plant glucoside, protodioscin, and did not split cellobiose. All the beta-glucosidases studied did not hydrolyze laminaribose, beta-D-methylsylopyranoside, alder O-methylglucuronoxylane, o-nitrophenyl-beta-D-galactopyranoside and p-nitrophenyl-alpha-D-glucopyranoside. beta-Cellobiase with pI 6.2 hydrolzed lactoses, cellobioses with pI 3.8 and pI 5.6 splited gentiobiose. beta-Glucosidase with pI 4.6 did not attack any substrate studied, except cellobiose.", "contents": "[beta-Glucosidases from fungus Geotrichum candidum]. beta-Glucosidases from Geotrichum candidum 3C cellulase preparation were separated from C1 enzymes and beta-1,4-glucanases by means of DEAE-Sephadex A-50 chromatography, gel filtration through P-150 Biogel and chromatography on CM-cellulose, and then were fractionated by isoelectric focusing using carrier ampholites with pH ranges 3-6 and 4-6. beta-Glucosidases with pI 3.8, 4.2, 4.6, 5.1, 5.6 and 6.2 were found in cellulase preparation from G. candidum 3C. Molecular weight of beta-glucosidases with pI 3.8, 4.2, 4.6 and 6.2, isolated under isoelectric focusing, were estimated by means of gel filtration through Sephadex G-200 to be 35000, 123000, 188000 and 223000 respectively. beta-Glucosidases with pI 3.8, 4.6, 5.6 and 6.2 hydrolyzed cellobiose and did not attack p-nitrophenyl-beta-D-glucopyranoside; those with pI 4.2 and 5.6 hydrolyzed p-nitrophenyl-beta-D-glucopyranoside and plant glucoside, protodioscin, and did not split cellobiose. All the beta-glucosidases studied did not hydrolyze laminaribose, beta-D-methylsylopyranoside, alder O-methylglucuronoxylane, o-nitrophenyl-beta-D-galactopyranoside and p-nitrophenyl-alpha-D-glucopyranoside. beta-Cellobiase with pI 6.2 hydrolzed lactoses, cellobioses with pI 3.8 and pI 5.6 splited gentiobiose. beta-Glucosidase with pI 4.6 did not attack any substrate studied, except cellobiose."}
{"id": "PMID:15652", "title": "[Optical and magnetic properties of azurin from Pseudomanas aeruginosa].", "content": "Optical, fluorescence and EPR spectra of azurin from Pseudomonas aeruginosa are described. Some properties of this protein are found to be similar to those of copper-containing proteins from plants (plastocyanin and plantacyanin). The interaction of ferricyanide with azurin bleached in alkaline media results in the formation of  free radicals and an alteration in the shape of the EPR signal of azurin.", "contents": "[Optical and magnetic properties of azurin from Pseudomanas aeruginosa]. Optical, fluorescence and EPR spectra of azurin from Pseudomonas aeruginosa are described. Some properties of this protein are found to be similar to those of copper-containing proteins from plants (plastocyanin and plantacyanin). The interaction of ferricyanide with azurin bleached in alkaline media results in the formation of  free radicals and an alteration in the shape of the EPR signal of azurin."}
{"id": "PMID:15653", "title": "[Investigation of rat brain prealbumins].", "content": "12 prealbumines of rat brain water-soluble fraction were studied. Neither lipid components nor carbohydrate ones were found out in the proteins. Three of the proteins appeared to be RNA-proteids. Their subcellular distribution was investigated. The effects of temperature, salts, acids and ethanol on disc electrophoretic spectrum of brain prealbumines were closely observed. The amino acid composition, properties, compartmentation, tissue and species specificity of one of the prealbumines were studied in detail. The protein is marked as BTB-protein, as it migrates under disc electrophoresis in 7,5% polyacrylamide gel with the \"witness\" front of bromothemol blue (BTB). The content of BTB-protein is 0.06--0.08 gr per 100 gr of wet tissue. The protein is RNA-proteid. Its molecular weight is 10,000--20,000. BTB-protein contains 42 mole % of acidic amino acids and 5.4 mole % of alkaline ones. The protein was found in nuclear and cytoplasmic fractions. It is mainly an all-organs protein. Small amount of this protein is found in blood serum. BTB-protein can be found on the disc electrophoregramms of embryo and newborn rats brain proteins, as well as of the brain of other mammals, birds and amphibia. BTB-protein is resistant to boiling and to the effects of salts, acids, ethanol. It is suggested that BTB-protein has heterogenous structure and may be of neurophysin nature.", "contents": "[Investigation of rat brain prealbumins]. 12 prealbumines of rat brain water-soluble fraction were studied. Neither lipid components nor carbohydrate ones were found out in the proteins. Three of the proteins appeared to be RNA-proteids. Their subcellular distribution was investigated. The effects of temperature, salts, acids and ethanol on disc electrophoretic spectrum of brain prealbumines were closely observed. The amino acid composition, properties, compartmentation, tissue and species specificity of one of the prealbumines were studied in detail. The protein is marked as BTB-protein, as it migrates under disc electrophoresis in 7,5% polyacrylamide gel with the \"witness\" front of bromothemol blue (BTB). The content of BTB-protein is 0.06--0.08 gr per 100 gr of wet tissue. The protein is RNA-proteid. Its molecular weight is 10,000--20,000. BTB-protein contains 42 mole % of acidic amino acids and 5.4 mole % of alkaline ones. The protein was found in nuclear and cytoplasmic fractions. It is mainly an all-organs protein. Small amount of this protein is found in blood serum. BTB-protein can be found on the disc electrophoregramms of embryo and newborn rats brain proteins, as well as of the brain of other mammals, birds and amphibia. BTB-protein is resistant to boiling and to the effects of salts, acids, ethanol. It is suggested that BTB-protein has heterogenous structure and may be of neurophysin nature."}
{"id": "PMID:15654", "title": "[Inhibition of mouse spleen inorganic pyrophosphatase by methylene diphosphonic acid].", "content": "Some properties of mouse spleen cytosol inorgainc pyrophosphatase (PPi-ase) (E. C. 3.6.1.1) as well as the effect of methylene diphosphonic acid (PCP) on the PPi-ase activity were studied. Specific staining for the enzyme PAAG disc-electrophoresis was developed; it was shown that the PPi-ase formed only one band in 7.5% PAAG. The enzyme pH optimum being 8.0, the optimal [Mg++]/[PPi] ratio was about 2; Km =7.7x10(-4) M, Vmax=0.77 mkM. min-1. mg protein-1. PCP was shown to competitively inhibit the pyrophosphatase reaction, Ki=2.5x10(-4) M +/- 0.2x10(-4) M.", "contents": "[Inhibition of mouse spleen inorganic pyrophosphatase by methylene diphosphonic acid]. Some properties of mouse spleen cytosol inorgainc pyrophosphatase (PPi-ase) (E. C. 3.6.1.1) as well as the effect of methylene diphosphonic acid (PCP) on the PPi-ase activity were studied. Specific staining for the enzyme PAAG disc-electrophoresis was developed; it was shown that the PPi-ase formed only one band in 7.5% PAAG. The enzyme pH optimum being 8.0, the optimal [Mg++]/[PPi] ratio was about 2; Km =7.7x10(-4) M, Vmax=0.77 mkM. min-1. mg protein-1. PCP was shown to competitively inhibit the pyrophosphatase reaction, Ki=2.5x10(-4) M +/- 0.2x10(-4) M."}
{"id": "PMID:15655", "title": "[The role of the tryptophan-62 residue in the structure and function of lysozyme].", "content": "The thermostability and thermodinamics of formation of the enzyme-substrate complex of two oxidation products of chicken egg lysozyme with the tryptophane-62 residue modified to N'-formylkinurenine (with 2.5% activity) and kinurenine (with 27.5% activity) have been studied. In thermostability and pH effect on the substrate binding the lysozyme oxidation products do not differ from native lysozyme. The data obtained and thermodynamical characteristics of the enzyme-substrate complex formation suggest that the chemical nature of the 62 residue does not significantly affect the  conformational properties of lysozyme, however, having a strongly pronounced effect on the binding of substrate and hence the total enzyme activity.", "contents": "[The role of the tryptophan-62 residue in the structure and function of lysozyme]. The thermostability and thermodinamics of formation of the enzyme-substrate complex of two oxidation products of chicken egg lysozyme with the tryptophane-62 residue modified to N'-formylkinurenine (with 2.5% activity) and kinurenine (with 27.5% activity) have been studied. In thermostability and pH effect on the substrate binding the lysozyme oxidation products do not differ from native lysozyme. The data obtained and thermodynamical characteristics of the enzyme-substrate complex formation suggest that the chemical nature of the 62 residue does not significantly affect the  conformational properties of lysozyme, however, having a strongly pronounced effect on the binding of substrate and hence the total enzyme activity."}
{"id": "PMID:15656", "title": "[Study of rat brain tissue nucleases].", "content": "Acid and alkaline nucleases of the brain tissues have been identified and partially purified. Alkaline DNA-ase hydrolyzing denatured DNA at pH 8,0; alkaline RNA-ase having optimal activity at pH 8,0 and nuclease intensively hydrolyzing both DNA and RNA at pH 5.0. The molecular weights of these enzymes have been determined.", "contents": "[Study of rat brain tissue nucleases]. Acid and alkaline nucleases of the brain tissues have been identified and partially purified. Alkaline DNA-ase hydrolyzing denatured DNA at pH 8,0; alkaline RNA-ase having optimal activity at pH 8,0 and nuclease intensively hydrolyzing both DNA and RNA at pH 5.0. The molecular weights of these enzymes have been determined."}
{"id": "PMID:15657", "title": "[Purification, properties and quaternary structure of glutamine synthetase from Chlorella].", "content": "A highly purified preparation of glutamine synthetase from chlorella grown on a medium containing nitrate as a sole source of nitrogen, was isolated and characterized by disc-electrophoresis and analytical ultracentrifugation. The N-terminal amino acid of glutamine synthetase is glycine. The molecular weight of glutamine synthetase is 32.000; its activity in the presence of Mg2+ was 150 mkmol o-phosphate per min per mg protein. The molecular weight of subunits of the enzyme, equal to 53.000 was determined by disc-electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate. Electron microscopy of negatively contrasted enzyme preparations revealed 6 subunits in the enzyme molecule, arranged in a point symmetry group 32.", "contents": "[Purification, properties and quaternary structure of glutamine synthetase from Chlorella]. A highly purified preparation of glutamine synthetase from chlorella grown on a medium containing nitrate as a sole source of nitrogen, was isolated and characterized by disc-electrophoresis and analytical ultracentrifugation. The N-terminal amino acid of glutamine synthetase is glycine. The molecular weight of glutamine synthetase is 32.000; its activity in the presence of Mg2+ was 150 mkmol o-phosphate per min per mg protein. The molecular weight of subunits of the enzyme, equal to 53.000 was determined by disc-electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate. Electron microscopy of negatively contrasted enzyme preparations revealed 6 subunits in the enzyme molecule, arranged in a point symmetry group 32."}
{"id": "PMID:15658", "title": "[Some physicochemical properties of modified trypsin].", "content": "Physico-chemical properties of trypsin covalently bound with human serum albumin by glutaric aldehyde have been studied. The modification of the enzyme practically caused no changes in the pH optimum of trypsin. The inhibition of modified trypsin by inhibitors from soy beans and human blood serum has been also studied. The apparent inhibition constants have been calculated. The modification has been shown to result in a deceleration of autolytic degradation. The autolysis rate constants have been calculated at 50 degrees C.", "contents": "[Some physicochemical properties of modified trypsin]. Physico-chemical properties of trypsin covalently bound with human serum albumin by glutaric aldehyde have been studied. The modification of the enzyme practically caused no changes in the pH optimum of trypsin. The inhibition of modified trypsin by inhibitors from soy beans and human blood serum has been also studied. The apparent inhibition constants have been calculated. The modification has been shown to result in a deceleration of autolytic degradation. The autolysis rate constants have been calculated at 50 degrees C."}
{"id": "PMID:15659", "title": "[Fractionation and purification of endo-1,4-beta-xylanases and exo-1,4-beta-xylosidases of Aspergillus niger].", "content": "Two endo-1,4-beta-zylanases (m. w. 24,000 and 41,000) and six exo-1,4-beta-xylosidases, differing in their molecular weights and isoelectric points, were found in a xylanase preparation from Aspergillus niger, using different methods of fractionation. An electrophoretically homogeneous exo-1,4-beta-xylosidase (m. w. 30,000) purified 120-fold, with pI 4.6, having optimal effect on methyl-beta-D-xyloside at pH 3.0 was obtained. Exo-1,4-beta-xylosidase splits off xylose from the ends of the xylan chains at xylotriose, xylobiose and methyl-beta-D-xyloside and is characterized by a high transglycosilase activity. An electrophoretically homogeneous endo-1,4-beta-xylanase (m. w. 24,000) purified 250-fold, with pI 4.2 and optimal effect on carboxymethylxylan at pH 4.2 was isolated. Endo-1,4-beta-xylanase splits arabinoglucuronoxylan to form xylooligosaccharides; however, it does not hydrolyze xylobiose.", "contents": "[Fractionation and purification of endo-1,4-beta-xylanases and exo-1,4-beta-xylosidases of Aspergillus niger]. Two endo-1,4-beta-zylanases (m. w. 24,000 and 41,000) and six exo-1,4-beta-xylosidases, differing in their molecular weights and isoelectric points, were found in a xylanase preparation from Aspergillus niger, using different methods of fractionation. An electrophoretically homogeneous exo-1,4-beta-xylosidase (m. w. 30,000) purified 120-fold, with pI 4.6, having optimal effect on methyl-beta-D-xyloside at pH 3.0 was obtained. Exo-1,4-beta-xylosidase splits off xylose from the ends of the xylan chains at xylotriose, xylobiose and methyl-beta-D-xyloside and is characterized by a high transglycosilase activity. An electrophoretically homogeneous endo-1,4-beta-xylanase (m. w. 24,000) purified 250-fold, with pI 4.2 and optimal effect on carboxymethylxylan at pH 4.2 was isolated. Endo-1,4-beta-xylanase splits arabinoglucuronoxylan to form xylooligosaccharides; however, it does not hydrolyze xylobiose."}
{"id": "PMID:15660", "title": "[Enzymatic properties of immobilized beta-galactosidase from Curvularia inaequalis].", "content": "beta-Galactosidase (EC 3.2.1.23) from fungus Curvularia inaequalis was modified by active brilliant orange KH and adsorbed on DEAE-Sephadex A-50. The lactose hydrolysis was studied in a continous flow on the column packed with the immobilized enzyme. The pH and temperatures optima for the substrate hydrolysis by the immobilized enzyme were shown to remain unchanged. A certain destabilizing effect of the matrix on the enzyme resistance to hear denaturation was observed. The activation parameters of denaturation of the native enzyme as well as those of the dye-modified and immobilized preparations were determined.", "contents": "[Enzymatic properties of immobilized beta-galactosidase from Curvularia inaequalis]. beta-Galactosidase (EC 3.2.1.23) from fungus Curvularia inaequalis was modified by active brilliant orange KH and adsorbed on DEAE-Sephadex A-50. The lactose hydrolysis was studied in a continous flow on the column packed with the immobilized enzyme. The pH and temperatures optima for the substrate hydrolysis by the immobilized enzyme were shown to remain unchanged. A certain destabilizing effect of the matrix on the enzyme resistance to hear denaturation was observed. The activation parameters of denaturation of the native enzyme as well as those of the dye-modified and immobilized preparations were determined."}
{"id": "PMID:15661", "title": "[Use of sedimentation under conditions of acidic denaturation for the determination of molecular weights of RNAs].", "content": "The conditions for acidic denaturation of double stranded RNA were found. Under these conditions a limited degradation of high molecular weight viral RNA took place. This degradation was determined by the degree of fragmentation and loss of infectivity at acidic conditions. It was found that acidic denaturation of RNA in the solutions of low ionic strength was accompanied by a considerable increase of sedimentation coefficient. Under these conditions the coefficients of sedimentation and molecular weights of RNAs studied are connected by the following function S20=2.84-10(-2) Mr0.689. The conclusion has been drawn that the sedimentation under the conditions for acidic denaturation could be used both for molecular weight determination and the practical preparation of unaggregated strands of RNA.", "contents": "[Use of sedimentation under conditions of acidic denaturation for the determination of molecular weights of RNAs]. The conditions for acidic denaturation of double stranded RNA were found. Under these conditions a limited degradation of high molecular weight viral RNA took place. This degradation was determined by the degree of fragmentation and loss of infectivity at acidic conditions. It was found that acidic denaturation of RNA in the solutions of low ionic strength was accompanied by a considerable increase of sedimentation coefficient. Under these conditions the coefficients of sedimentation and molecular weights of RNAs studied are connected by the following function S20=2.84-10(-2) Mr0.689. The conclusion has been drawn that the sedimentation under the conditions for acidic denaturation could be used both for molecular weight determination and the practical preparation of unaggregated strands of RNA."}
{"id": "PMID:15662", "title": "[Purification and properties of phototrophic bacteria Thiocapsa roseopersicina hydrogenase bound with chromatophores].", "content": "The method of solution and puridication of hydrogenase from chromatophores of purpur sulphur bacteria Thiocapsa roseopersicina strain BBS are described. Hydrogenase molecular weight is 73000. It contains 4,4 mole S2- and 3.1 mole Fe2+ per mole of protein; pI 4.15. The enzyme absorption spectrum has the maximun et 400-410 nm, which is characteristic of proteins containing non-haem iron. Membrane--linked enzyme as well as soluble hydrogenase of that microorganism is characterized by high thermal stability: inactivation occurs at the temperature above 78 degrees C when the optimal temperature for that enzyme is 70 degrees C. Homogenous enzyme catalyses D2--H2O exchange reaction, reversible redox reaction of methyl viologene and benzyl viologene.", "contents": "[Purification and properties of phototrophic bacteria Thiocapsa roseopersicina hydrogenase bound with chromatophores]. The method of solution and puridication of hydrogenase from chromatophores of purpur sulphur bacteria Thiocapsa roseopersicina strain BBS are described. Hydrogenase molecular weight is 73000. It contains 4,4 mole S2- and 3.1 mole Fe2+ per mole of protein; pI 4.15. The enzyme absorption spectrum has the maximun et 400-410 nm, which is characteristic of proteins containing non-haem iron. Membrane--linked enzyme as well as soluble hydrogenase of that microorganism is characterized by high thermal stability: inactivation occurs at the temperature above 78 degrees C when the optimal temperature for that enzyme is 70 degrees C. Homogenous enzyme catalyses D2--H2O exchange reaction, reversible redox reaction of methyl viologene and benzyl viologene."}
{"id": "PMID:15663", "title": "[Conformation study of cyclic adenosine-3',5'-monophosphate and some of its derivatives by means of circular dichroism].", "content": "Circular dichroism spectra of adenosine and cyclic adenosine-3',5'-monophosphate (cAMP) and their derivatives, having different substituents in 8-position of heterocycle, are studied, cAMP is suggested to have preferable anti-conformation in the solution, while its derivatives with substituents in 8-position of purine base are preferable in sin-conformation. An exception is 8-(beta aminoethylamine-)cAMP, which has an anti-conformation within pH range from 4.5 to 9.5. This is probably due to the formation of intra-molecular ionic bond between cyclophosphate group and aliphatic amino group of 8-position substituent.", "contents": "[Conformation study of cyclic adenosine-3',5'-monophosphate and some of its derivatives by means of circular dichroism]. Circular dichroism spectra of adenosine and cyclic adenosine-3',5'-monophosphate (cAMP) and their derivatives, having different substituents in 8-position of heterocycle, are studied, cAMP is suggested to have preferable anti-conformation in the solution, while its derivatives with substituents in 8-position of purine base are preferable in sin-conformation. An exception is 8-(beta aminoethylamine-)cAMP, which has an anti-conformation within pH range from 4.5 to 9.5. This is probably due to the formation of intra-molecular ionic bond between cyclophosphate group and aliphatic amino group of 8-position substituent."}
{"id": "PMID:15665", "title": "The relationship between epilepsy and schizophrenia: a biochemical hypothesis.", "content": "There has been much controversy in the past surrounding the relationship between schizophrenia and epilepsy. One hypothesis has been that the two disorders are antagonistic. The evidence supporting the antagonism hypothesis is briefly reviewed. A new theory based on current knowledge of the relationship of dopamine to both disorders is postulated which may explain the relationship between the psychosis and epilepsy which occurs in a subgroup of schizophrenic patients. In the light of this hypothesis it is suggested that further clinical work be undertaken to clarify further the exact association between the two disorders.", "contents": "The relationship between epilepsy and schizophrenia: a biochemical hypothesis. There has been much controversy in the past surrounding the relationship between schizophrenia and epilepsy. One hypothesis has been that the two disorders are antagonistic. The evidence supporting the antagonism hypothesis is briefly reviewed. A new theory based on current knowledge of the relationship of dopamine to both disorders is postulated which may explain the relationship between the psychosis and epilepsy which occurs in a subgroup of schizophrenic patients. In the light of this hypothesis it is suggested that further clinical work be undertaken to clarify further the exact association between the two disorders."}
{"id": "PMID:15667", "title": "High and low affinity Ca2+ binding to the sarcoplasmic reticulum: use of a high-affinity fluorescent calcium indicator.", "content": "The fluorescent calcium indicator, calcein, has been used as a high-affinity indicator of Ca2+ in the aqueous phase at physiological pH in the study of high-affinity calcium binding to sarcoplasmic reticulum (SR). The binding constant of the indicator at physiological pH is 10(3)-10(4) M-1 and increases with increasing pH. The binding mechanism of the indicator with Ca2+ and Mg2+ is described. Application of calcein as an aqueous indicator of Ca2+ binding to the SR at room temperature has revealed two classes of binding sites: one with high capacity and low affinity (ca. 820 nmol/mg protein, Kd = 1.9 mM), and another with low capacity and higher affinity (ca. 35 nmol/mg protein, Kd = 17.5 micronM). The divalent cation specificity of the low-affinity  site is low and Ca2+/Mg2+ specificity of the high-affinity site is high. Quantitative studies of the bindings indicate that the high-affinity site residues in the Ca2+ ATPase (carrier) protein and represents complexation in the active site of the carrier and that the low-affinity site residues in the nonspecific acidic binding proteins. The contribution of Donnan equilibrium effects to the measured binding is shown to be insignificant. Stopped flow kinetic studies of Ca2+ passive binding with calcein and arsenazo III dyes have demonstrated that the binding to high-affinity site is very fast and that the overall binding reaction with the low-affinity site is slow, with a time course of about 4 s. Our analysis has shown that at least part of the low-affinity acidic proteins are within the SR matrix and that Ca2+ can reach them only by transversing the membrane via the Ca2+ carrier (Ca2+ ATPase). A model of the SR is proposed that accounts for several functional properties of the organelle in terms of its known protein composition and topological organization.", "contents": "High and low affinity Ca2+ binding to the sarcoplasmic reticulum: use of a high-affinity fluorescent calcium indicator. The fluorescent calcium indicator, calcein, has been used as a high-affinity indicator of Ca2+ in the aqueous phase at physiological pH in the study of high-affinity calcium binding to sarcoplasmic reticulum (SR). The binding constant of the indicator at physiological pH is 10(3)-10(4) M-1 and increases with increasing pH. The binding mechanism of the indicator with Ca2+ and Mg2+ is described. Application of calcein as an aqueous indicator of Ca2+ binding to the SR at room temperature has revealed two classes of binding sites: one with high capacity and low affinity (ca. 820 nmol/mg protein, Kd = 1.9 mM), and another with low capacity and higher affinity (ca. 35 nmol/mg protein, Kd = 17.5 micronM). The divalent cation specificity of the low-affinity  site is low and Ca2+/Mg2+ specificity of the high-affinity site is high. Quantitative studies of the bindings indicate that the high-affinity site residues in the Ca2+ ATPase (carrier) protein and represents complexation in the active site of the carrier and that the low-affinity site residues in the nonspecific acidic binding proteins. The contribution of Donnan equilibrium effects to the measured binding is shown to be insignificant. Stopped flow kinetic studies of Ca2+ passive binding with calcein and arsenazo III dyes have demonstrated that the binding to high-affinity site is very fast and that the overall binding reaction with the low-affinity site is slow, with a time course of about 4 s. Our analysis has shown that at least part of the low-affinity acidic proteins are within the SR matrix and that Ca2+ can reach them only by transversing the membrane via the Ca2+ carrier (Ca2+ ATPase). A model of the SR is proposed that accounts for several functional properties of the organelle in terms of its known protein composition and topological organization."}
{"id": "PMID:15668", "title": "Structural changes and fluctuations of proteins. II. Analysis of the denaturation of globular proteins.", "content": "The statistical thermodynamic model of protein structure proposed in paper I is developed with special attention to the hydrophobic interaction. Calorimetric measurements of the thermal denaturation of five globular proteins, ribonuclease A, lysozyme, alpha-chymotrypsin, cytochrome c, and myoglobin, are quantitatively analyzed using the model. The thermodynamic parameters obtained by the least squares method reflect the global, average properties of proteins and are in good agreement with the expected values estimated from experimental and theoretical studies for model peptides. The average bond energy epsilon is well related to the tertiary structure of each protein. However, the difference in the parameters between different proteins is not observed for the cooperative energy ZJ and the chain entropy alpha. The individuality of a protein as far as its structural stability is concerned, is mainly reflected by the parameter gamma specifying the hydrophobic nature of a protein. The model is further applied in the analysis of several aspects of the structural stability of globular proteins. Denaturation induced by denaturants, salts, and pH are also explained by the model in a unified manner.", "contents": "Structural changes and fluctuations of proteins. II. Analysis of the denaturation of globular proteins. The statistical thermodynamic model of protein structure proposed in paper I is developed with special attention to the hydrophobic interaction. Calorimetric measurements of the thermal denaturation of five globular proteins, ribonuclease A, lysozyme, alpha-chymotrypsin, cytochrome c, and myoglobin, are quantitatively analyzed using the model. The thermodynamic parameters obtained by the least squares method reflect the global, average properties of proteins and are in good agreement with the expected values estimated from experimental and theoretical studies for model peptides. The average bond energy epsilon is well related to the tertiary structure of each protein. However, the difference in the parameters between different proteins is not observed for the cooperative energy ZJ and the chain entropy alpha. The individuality of a protein as far as its structural stability is concerned, is mainly reflected by the parameter gamma specifying the hydrophobic nature of a protein. The model is further applied in the analysis of several aspects of the structural stability of globular proteins. Denaturation induced by denaturants, salts, and pH are also explained by the model in a unified manner."}
{"id": "PMID:15669", "title": "Oligonucleotide conformations. (5) NMR and relaxation studies on GpU and UpG at neutral pH.", "content": "The average conformation of GpU and UpG in neutral aqueous solutions has been investigated by proton chemical shifts and coupling measurements as well as T1 relaxation time experiments. The proportion of the N and S pseudorotational conformers of the ribose ring has been derived from the vicinal coupling constants. The relaxation data provide information about the syn--anti equilibrium of the orientation of the base about the glycosidic bond. This orientation is predominantly syn for the Guo base in both dinucleoside phosphates, that of Urd is anti in the case of GpU and shows an almost equivalent syn and anti character for UpG.", "contents": "Oligonucleotide conformations. (5) NMR and relaxation studies on GpU and UpG at neutral pH. The average conformation of GpU and UpG in neutral aqueous solutions has been investigated by proton chemical shifts and coupling measurements as well as T1 relaxation time experiments. The proportion of the N and S pseudorotational conformers of the ribose ring has been derived from the vicinal coupling constants. The relaxation data provide information about the syn--anti equilibrium of the orientation of the base about the glycosidic bond. This orientation is predominantly syn for the Guo base in both dinucleoside phosphates, that of Urd is anti in the case of GpU and shows an almost equivalent syn and anti character for UpG."}
{"id": "PMID:15670", "title": "Kinetics of the polymerization reaction of tobacco mosaic virus protein: transient-saturation type polymerization reaction.", "content": "The kinetics of the endothermic polymerization reaction of tobacco mosaic virus protein in the mild acid region was studied by means of temperature-jump (rising time of 6 sec)-turbidimetry, electron microscopy, and computer simulation. The time course profile of the turbidity increase changed from a normal one to an anomalous one as the size of the temperature-jump was made greater. The anomalous type polymerization profile, which we named the \"transient-saturation\" type, could be characterized by a rapid increase of turbidity and its transient saturation, and a slow increase to the final level. At a higher concentration of the protein, this transient-saturation effect was more marked, whereas the slow turbidity in the second phase occurred with a higher rate. This transient-saturation type polymerization profile was observed also in a pH-induced polymerization reaction. It was not observed in the case of the N-bromosuccinimide modified tobacco mosaic virus protein under a similar environmental change. By an electron microscopic study and computer simulation, it was revealed that in the first phase, a large number of short polymers were formed, and the concentration of the polymerizing units was rapidly reduced to the equilibrium value, and the polymerization reaction stopped transiently. In the second phase, polymer-polymer associations took place slowly and longer polymers were formed. The revlevance of the present study to the polymerization reaction of actin, myosin, and to a transient-overshoot type polymerization are discussed.", "contents": "Kinetics of the polymerization reaction of tobacco mosaic virus protein: transient-saturation type polymerization reaction. The kinetics of the endothermic polymerization reaction of tobacco mosaic virus protein in the mild acid region was studied by means of temperature-jump (rising time of 6 sec)-turbidimetry, electron microscopy, and computer simulation. The time course profile of the turbidity increase changed from a normal one to an anomalous one as the size of the temperature-jump was made greater. The anomalous type polymerization profile, which we named the \"transient-saturation\" type, could be characterized by a rapid increase of turbidity and its transient saturation, and a slow increase to the final level. At a higher concentration of the protein, this transient-saturation effect was more marked, whereas the slow turbidity in the second phase occurred with a higher rate. This transient-saturation type polymerization profile was observed also in a pH-induced polymerization reaction. It was not observed in the case of the N-bromosuccinimide modified tobacco mosaic virus protein under a similar environmental change. By an electron microscopic study and computer simulation, it was revealed that in the first phase, a large number of short polymers were formed, and the concentration of the polymerizing units was rapidly reduced to the equilibrium value, and the polymerization reaction stopped transiently. In the second phase, polymer-polymer associations took place slowly and longer polymers were formed. The revlevance of the present study to the polymerization reaction of actin, myosin, and to a transient-overshoot type polymerization are discussed."}
{"id": "PMID:15671", "title": "Our present knowledge of calcium or hydrogen ions as transmitters in the vertebrate rod outer segments.", "content": "Difficulties in testing the possible role of calcium as a Transmitter in the R.O.S. are discussed. A comparison is made with the Sarcoplasmic Reticulum system where calcium flux are easily measured. The latest results reviewed on intact cellular structures are highly indicative but not yet conclusive.", "contents": "Our present knowledge of calcium or hydrogen ions as transmitters in the vertebrate rod outer segments. Difficulties in testing the possible role of calcium as a Transmitter in the R.O.S. are discussed. A comparison is made with the Sarcoplasmic Reticulum system where calcium flux are easily measured. The latest results reviewed on intact cellular structures are highly indicative but not yet conclusive."}
{"id": "PMID:15672", "title": "Properties of intracellular ribonuclease utilized for RNA reduction in disintegrated cells of Saccharomyces cerevisiae.", "content": "The properties of intracellular RNase in disintegrated cell suspensions of Saccharomyces cerevisiae have been studied. The influence of salt addition and/or incubation of the suspension on the activity of RNase and on the degradation of endogenous RNA was determined. No significant change in the RNase activity in the disintegrated suspensions was obtained by addition of 3% NaCl or by incubation at 50 degrees C with 3% NaCl. During the incubation with NaCl the active RNase was able to degrade endogenous RNA. By incubation without salt the RNase was inactivated. Inactivation also occurred after extraction at alkaline pH. The RNase had an optima at pH 5-6 and temperatures between 50-60 degrees C. The main part of the RNase in the unincubated suspension was soluble also at pH 4.0. No serious protein degradation occurred during the short time incubation needed for RNA reduction. 70% of the protein in the suspensions was recovered in the precipitate at pH 4.0 after 20 min of incubation. The corresponding protein recovery from unincubated suspensions was 77%.", "contents": "Properties of intracellular ribonuclease utilized for RNA reduction in disintegrated cells of Saccharomyces cerevisiae. The properties of intracellular RNase in disintegrated cell suspensions of Saccharomyces cerevisiae have been studied. The influence of salt addition and/or incubation of the suspension on the activity of RNase and on the degradation of endogenous RNA was determined. No significant change in the RNase activity in the disintegrated suspensions was obtained by addition of 3% NaCl or by incubation at 50 degrees C with 3% NaCl. During the incubation with NaCl the active RNase was able to degrade endogenous RNA. By incubation without salt the RNase was inactivated. Inactivation also occurred after extraction at alkaline pH. The RNase had an optima at pH 5-6 and temperatures between 50-60 degrees C. The main part of the RNase in the unincubated suspension was soluble also at pH 4.0. No serious protein degradation occurred during the short time incubation needed for RNA reduction. 70% of the protein in the suspensions was recovered in the precipitate at pH 4.0 after 20 min of incubation. The corresponding protein recovery from unincubated suspensions was 77%."}
{"id": "PMID:15673", "title": "Fermentation of glucose by Acetobacter melanogenus.", "content": "Growing cultures of Acetobacter melanogenus ATCC 9937 concerted D-glucose to 2,5-diketo-D-gluconic acid with D-gluconic acid and 5-keto-D-gluconic acid as intermediates. The 2,5-diketo-D-gluconic acid was isolated from the fermented medium by treatment with an anion exchange resin.", "contents": "Fermentation of glucose by Acetobacter melanogenus. Growing cultures of Acetobacter melanogenus ATCC 9937 concerted D-glucose to 2,5-diketo-D-gluconic acid with D-gluconic acid and 5-keto-D-gluconic acid as intermediates. The 2,5-diketo-D-gluconic acid was isolated from the fermented medium by treatment with an anion exchange resin."}
{"id": "PMID:15674", "title": "Growth characteristics of Candida utilis on volatile substrate in a multistage tower fermentor.", "content": "The influence of increasing ethanol concentration in the feed on growth and physiological activity of the yeast Candida utlis was studied. The measurements were made at steady states of continuous culture under constant values of dilution rate, temperature, and pH in all stages of the fermentor; Synthetic ethanol was used as the sole source of carbon and energy in the concentration range 10-100 g/liter. The maximum biomass concentration in the effluent and maximum productivity was achieved at 75 g ethanol/liter in the feed. In respect to ethanol losses in the outlet and biomass yield, the optimum ethanol concentration in the input of the growth medium was found to be about 50 g/liter using a four-stage system.", "contents": "Growth characteristics of Candida utilis on volatile substrate in a multistage tower fermentor. The influence of increasing ethanol concentration in the feed on growth and physiological activity of the yeast Candida utlis was studied. The measurements were made at steady states of continuous culture under constant values of dilution rate, temperature, and pH in all stages of the fermentor; Synthetic ethanol was used as the sole source of carbon and energy in the concentration range 10-100 g/liter. The maximum biomass concentration in the effluent and maximum productivity was achieved at 75 g ethanol/liter in the feed. In respect to ethanol losses in the outlet and biomass yield, the optimum ethanol concentration in the input of the growth medium was found to be about 50 g/liter using a four-stage system."}
{"id": "PMID:15677", "title": "The enzymatic conversion of L-histidine to urocanic acid by whole cells of Micrococcus luteus immobilized on carbodiimide activated carboxymethylcellulose.", "content": "Whole cells of Micrococcus luteus (formerly Sarcina lutea ATCC 9341) have been covalently linked to a carboxymethylcellulose support system, with the retention of histidine ammonia-lyase activity. The dependence of the rate of urocanic acid formation on pH, temperature, and added surfactant concentration was similar for the free and the immobilized cells. The immobilization procedure used is based on the carbodiimide activation of carboxymethylcellulose and has been optimized for the histidine ammonia-lyase activity of the immobilized cells on a given weight of cellulose. In a column reactor at 23 degrees C and superficial velocity of 0.044 cm/min, 5 g of cellulose with bound cells gave a 35% conversion of an L-histidine solution (0.25M, pH 9.0) to urocanic acid for 16 days of continuous operation. The scope of this carbodiimide assisted immobilization procedure has been investigated for a series of microorganisms and a variety of carboxylate functionalized supports.", "contents": "The enzymatic conversion of L-histidine to urocanic acid by whole cells of Micrococcus luteus immobilized on carbodiimide activated carboxymethylcellulose. Whole cells of Micrococcus luteus (formerly Sarcina lutea ATCC 9341) have been covalently linked to a carboxymethylcellulose support system, with the retention of histidine ammonia-lyase activity. The dependence of the rate of urocanic acid formation on pH, temperature, and added surfactant concentration was similar for the free and the immobilized cells. The immobilization procedure used is based on the carbodiimide activation of carboxymethylcellulose and has been optimized for the histidine ammonia-lyase activity of the immobilized cells on a given weight of cellulose. In a column reactor at 23 degrees C and superficial velocity of 0.044 cm/min, 5 g of cellulose with bound cells gave a 35% conversion of an L-histidine solution (0.25M, pH 9.0) to urocanic acid for 16 days of continuous operation. The scope of this carbodiimide assisted immobilization procedure has been investigated for a series of microorganisms and a variety of carboxylate functionalized supports."}
{"id": "PMID:15678", "title": "Pepsin immobilized on inorganic supports for the continuous coagulation of skim milk.", "content": "The milk-clotting enzyme pepsin was immobilized onto beads of alumina, titania, glass, stainless steel, iron oxide, and Teflon for treating skim milk in a fluidized-bed reactor. Two covalent attachment procedures using silanized supports and glutaraldehyde and two adsorption procedures were evaluated. The three best catalysts were titania and glass, using the covalent attachment procedure, and alumina, using the adsorption procedure at pH 1.2. The pepsin adsorbed on alumina catalyst has commercial potential compared to the previously used glass catalyst. Attempts to increase the stability of pepsin adsorbed on alumina by cross-linking with glutaraldehyde were unsuccessful owing to the low pH necessary for optimum pepsin adsorption; Desorption of pepsin from alumina during reactor operation was determined. Regeneration of spent catalysts was only partially successful.", "contents": "Pepsin immobilized on inorganic supports for the continuous coagulation of skim milk. The milk-clotting enzyme pepsin was immobilized onto beads of alumina, titania, glass, stainless steel, iron oxide, and Teflon for treating skim milk in a fluidized-bed reactor. Two covalent attachment procedures using silanized supports and glutaraldehyde and two adsorption procedures were evaluated. The three best catalysts were titania and glass, using the covalent attachment procedure, and alumina, using the adsorption procedure at pH 1.2. The pepsin adsorbed on alumina catalyst has commercial potential compared to the previously used glass catalyst. Attempts to increase the stability of pepsin adsorbed on alumina by cross-linking with glutaraldehyde were unsuccessful owing to the low pH necessary for optimum pepsin adsorption; Desorption of pepsin from alumina during reactor operation was determined. Regeneration of spent catalysts was only partially successful."}
{"id": "PMID:15680", "title": "[Effect of abrogating hybrid resistance on the survival of radiation chimeras].", "content": "A study was made of the effect of the hybrid resistance abrogation by means of the lymphoid cell administration on the survival of the lethally irradiated mice protected by the transplantation of the semiallogeneic bone marrow. Injection to the C57BLxCBA recipients of the C57BL lymphoid cells one day before the irradiation and the transplantation of the bone marrow of the same genotype (C57BL) increased the chimera survival in comparison with the untreated recipients; such pretreatment 7 days before the irradiation decreased the chimera survival. Parental spleen lymphocytes administration produced but an insignificant effect on the radioresistance both of the stem hemopoietic cells (by the endocolonisation test) and of the organism as a whole (by the 30-day survival test) of the F1 hybrid. On this basis a conclusion was drawn that the differences in the splenocyte efficacy, when they were injected at different periods before the irradiation, could not be attributed to the changes in radioresistance.", "contents": "[Effect of abrogating hybrid resistance on the survival of radiation chimeras]. A study was made of the effect of the hybrid resistance abrogation by means of the lymphoid cell administration on the survival of the lethally irradiated mice protected by the transplantation of the semiallogeneic bone marrow. Injection to the C57BLxCBA recipients of the C57BL lymphoid cells one day before the irradiation and the transplantation of the bone marrow of the same genotype (C57BL) increased the chimera survival in comparison with the untreated recipients; such pretreatment 7 days before the irradiation decreased the chimera survival. Parental spleen lymphocytes administration produced but an insignificant effect on the radioresistance both of the stem hemopoietic cells (by the endocolonisation test) and of the organism as a whole (by the 30-day survival test) of the F1 hybrid. On this basis a conclusion was drawn that the differences in the splenocyte efficacy, when they were injected at different periods before the irradiation, could not be attributed to the changes in radioresistance."}
{"id": "PMID:15681", "title": "[Effect of 3-acetylpyridine on the functional activity of the adrenal cortex].", "content": "A reduction of blood corticosteroid content was observed in rats blood after the administration of 3-acetylpyridine. The rats given ACTH after 3-acetylpyridine showed a lesser elevation of corticosteroids in the blood and adrenal gland tissue than the intact animals; 3-acetylpyridine diminished the activity of dehydrogenase glucose-6-phosphate in the adrenal glands. The authors suggested that the action of acetylpyridine was realized at the adrenal gland level and consisted in inhibition of the NADP-H2 generation in the dehydrogenase systems.", "contents": "[Effect of 3-acetylpyridine on the functional activity of the adrenal cortex]. A reduction of blood corticosteroid content was observed in rats blood after the administration of 3-acetylpyridine. The rats given ACTH after 3-acetylpyridine showed a lesser elevation of corticosteroids in the blood and adrenal gland tissue than the intact animals; 3-acetylpyridine diminished the activity of dehydrogenase glucose-6-phosphate in the adrenal glands. The authors suggested that the action of acetylpyridine was realized at the adrenal gland level and consisted in inhibition of the NADP-H2 generation in the dehydrogenase systems."}
{"id": "PMID:15682", "title": "[Participation of non-specific rat liver microsome oxidases in destruction of Nl-furanidylpyrimidines].", "content": "N1-(3'-Butyrolactono)-5-fluorouracil, N1-(2'-furanidyl) 5-trifluoromethyluracil, N1-(2'-furanidyl)-5-fluoracil are split in the rat organism with the formation of free 5-fluorouracil. The destruction of the C--N bonds in the molecule of the N1-(2'-furanidyl)-5-fluoracil takes place in the liver microsomes. This process is strengthened by NADPH and weakened by SKF-525A. All the three furanidylpyrimidines studied induced differential spectra of type I in the suspension of the liver microsomes. This fact testifies to the interaction of these substances with the cytochrome P-450.", "contents": "[Participation of non-specific rat liver microsome oxidases in destruction of Nl-furanidylpyrimidines]. N1-(3'-Butyrolactono)-5-fluorouracil, N1-(2'-furanidyl) 5-trifluoromethyluracil, N1-(2'-furanidyl)-5-fluoracil are split in the rat organism with the formation of free 5-fluorouracil. The destruction of the C--N bonds in the molecule of the N1-(2'-furanidyl)-5-fluoracil takes place in the liver microsomes. This process is strengthened by NADPH and weakened by SKF-525A. All the three furanidylpyrimidines studied induced differential spectra of type I in the suspension of the liver microsomes. This fact testifies to the interaction of these substances with the cytochrome P-450."}
{"id": "PMID:15684", "title": "[Immunocompetent lymphoi- cells from pregnant mice studied in the graft-versus-host reaction].", "content": "The capacity of lymphoid cells taken from C57BL/6 mice gravid from the CBA males (the second trimester) to induce the graft-versus-host reaction in the hybrids (CBA X C57B/6) F1 was reduced as compared with the cells of the virgin donors and syngeneic gravid mice. This was expressed by the prolonged survival of the experimental recipients and reduced inhibition of endogenous colony formation in the spleen of the sublethally irradiated (500 r) hybrids. At the end of gravidity this capacity was restored, in some instances even exceeding control figures.", "contents": "[Immunocompetent lymphoi- cells from pregnant mice studied in the graft-versus-host reaction]. The capacity of lymphoid cells taken from C57BL/6 mice gravid from the CBA males (the second trimester) to induce the graft-versus-host reaction in the hybrids (CBA X C57B/6) F1 was reduced as compared with the cells of the virgin donors and syngeneic gravid mice. This was expressed by the prolonged survival of the experimental recipients and reduced inhibition of endogenous colony formation in the spleen of the sublethally irradiated (500 r) hybrids. At the end of gravidity this capacity was restored, in some instances even exceeding control figures."}
{"id": "PMID:15685", "title": "[Development of the graft versus host reaction and its influence on pregnancy in mice following heparin administration].", "content": "The influence of heparin on the graft-versus-host reaction (GVHR) and the peculiarities attending the development of pregnancy in female animals which survived after the GVHR were studied. Preliminary administration of heparin to the recipients prevented their death or increased their life span. An intensification of the GVHR was noted after the administration of heparin to donors or its addition to the transplanted cells. In mice which survived after the GVHR as a result of heparin administration the intrauterine fetuses death and abortions were noted in 60-100% of cases during subsequent pregnancy (3 to 6 months after the cell transplantation). In the case of repeated pregnancies of these female animal pathology of pregnancy was less frequent; however, some of the offspring displayed the rant syndrome. No such disturbances of pregnancy were observed in mice given heparin alone or in those which survived after the transplantation of lymphoid cells only. The sustained pregnancy promoted the intensification of the GVHR induced in the female animals earlier after the heparin administration.", "contents": "[Development of the graft versus host reaction and its influence on pregnancy in mice following heparin administration]. The influence of heparin on the graft-versus-host reaction (GVHR) and the peculiarities attending the development of pregnancy in female animals which survived after the GVHR were studied. Preliminary administration of heparin to the recipients prevented their death or increased their life span. An intensification of the GVHR was noted after the administration of heparin to donors or its addition to the transplanted cells. In mice which survived after the GVHR as a result of heparin administration the intrauterine fetuses death and abortions were noted in 60-100% of cases during subsequent pregnancy (3 to 6 months after the cell transplantation). In the case of repeated pregnancies of these female animal pathology of pregnancy was less frequent; however, some of the offspring displayed the rant syndrome. No such disturbances of pregnancy were observed in mice given heparin alone or in those which survived after the transplantation of lymphoid cells only. The sustained pregnancy promoted the intensification of the GVHR induced in the female animals earlier after the heparin administration."}
{"id": "PMID:15686", "title": "[Quantitative changes in gastric juice proteases in dogs during ulcer formation in the stomach].", "content": "Disc-electrophoretic investigation of proteases of the gastric juice of dogs under normal conditions and in experimental atophan ulcer of the stomach demonstrated that in fasting dogs ulceration was accompanied by marked quantitative changes in the protease spectrum. Fraction No. 6 showed a significant elevation against the background of total reduction of proteolytic fraction of the gastric juice in sham feeding of ulcerated dogs. Sham feeding replete ulcerated dogs indicated a marked increase of fractions No.1 and No.2. The noted changes of the gastric juice protease spectrum may be of ulcerogenic significance.", "contents": "[Quantitative changes in gastric juice proteases in dogs during ulcer formation in the stomach]. Disc-electrophoretic investigation of proteases of the gastric juice of dogs under normal conditions and in experimental atophan ulcer of the stomach demonstrated that in fasting dogs ulceration was accompanied by marked quantitative changes in the protease spectrum. Fraction No. 6 showed a significant elevation against the background of total reduction of proteolytic fraction of the gastric juice in sham feeding of ulcerated dogs. Sham feeding replete ulcerated dogs indicated a marked increase of fractions No.1 and No.2. The noted changes of the gastric juice protease spectrum may be of ulcerogenic significance."}
{"id": "PMID:15687", "title": "[Adrenergic component in the hepatotropic, carcinogenic effect of diethylnitrosamine].", "content": "The effect of norepinephine, an adrenomietic drug, and of pyrroxane, its antagonist, on diethylnitrosoamine (DENA) hepatocarcinogenesis was studied in albino rats. Norepinephrine was found to stimulate carcinogenesis, whereas pyrroxane--to inhibit this process; the latter drug decreased the incidence of multicentric tumours of the liver. In vitro experiments on the isolated rat atria showed low DENA concentrations (1x10(-6) to 1x10(-8) M) to sensitize the atrium adrenoreceptors to the endogenous and exogenous norepinephrine. A new hypothesis on the adrenergic component in the DENA carcinogenic effect caused by the endogenous norepinephrine is presented.", "contents": "[Adrenergic component in the hepatotropic, carcinogenic effect of diethylnitrosamine]. The effect of norepinephine, an adrenomietic drug, and of pyrroxane, its antagonist, on diethylnitrosoamine (DENA) hepatocarcinogenesis was studied in albino rats. Norepinephrine was found to stimulate carcinogenesis, whereas pyrroxane--to inhibit this process; the latter drug decreased the incidence of multicentric tumours of the liver. In vitro experiments on the isolated rat atria showed low DENA concentrations (1x10(-6) to 1x10(-8) M) to sensitize the atrium adrenoreceptors to the endogenous and exogenous norepinephrine. A new hypothesis on the adrenergic component in the DENA carcinogenic effect caused by the endogenous norepinephrine is presented."}
{"id": "PMID:15688", "title": "Current status of bone marrow transplantation for aplastic anemia and acute leukemia.", "content": "Clinical results of marrow transplantation in the treatment of aplastic anemia and acute leukemia are reviewed. The principal problem areas in this field at this time are discussed.", "contents": "Current status of bone marrow transplantation for aplastic anemia and acute leukemia. Clinical results of marrow transplantation in the treatment of aplastic anemia and acute leukemia are reviewed. The principal problem areas in this field at this time are discussed."}
{"id": "PMID:15689", "title": "Thrombin-induced vasodilation in the hindlimb (dog).", "content": "The objective of this study is to test the hypothesis that the vasodilation produced by intra-arterial injection of thrombin to the hindlimb of a dog may be caused by the secondary release or production of some vasodilating substance. The vasodilator response to thrombin was compared with the vasodilator response to acetylcholine, isoproterenol, histamine and serotonin before and after blockade with atropine, propranolol, phenergan or methyl-D-lysergic acid butanolamide (UML-491), respectively. Though the appropriate blocking agent blocked the vasodilator response to the respective drug, the thrombin-induced vasodilation was not blocked. These data support the hypothesis that thrombin-induced vasodilation is a response to the thrombin moiety.", "contents": "Thrombin-induced vasodilation in the hindlimb (dog). The objective of this study is to test the hypothesis that the vasodilation produced by intra-arterial injection of thrombin to the hindlimb of a dog may be caused by the secondary release or production of some vasodilating substance. The vasodilator response to thrombin was compared with the vasodilator response to acetylcholine, isoproterenol, histamine and serotonin before and after blockade with atropine, propranolol, phenergan or methyl-D-lysergic acid butanolamide (UML-491), respectively. Though the appropriate blocking agent blocked the vasodilator response to the respective drug, the thrombin-induced vasodilation was not blocked. These data support the hypothesis that thrombin-induced vasodilation is a response to the thrombin moiety."}
{"id": "PMID:15691", "title": "Anatomico-physiological considerations in exploration of the fourth ventricle.", "content": "The advancement of surgical techniques has enabled the neurosurgeon to undertake a continually more aggressive approach toward lesions within the fourth ventricle. Laboratory and clinical observations have enabled us to conclude that (1) exploration of the fourth ventricle is feasible without anatomical disruption of the vermis, (2) controlled ventilation during such explorations is physiologically most desirable, and (3) irrigation of neural structures must consider acid-base and ionic parameters in order to maintain physiologic stability.", "contents": "Anatomico-physiological considerations in exploration of the fourth ventricle. The advancement of surgical techniques has enabled the neurosurgeon to undertake a continually more aggressive approach toward lesions within the fourth ventricle. Laboratory and clinical observations have enabled us to conclude that (1) exploration of the fourth ventricle is feasible without anatomical disruption of the vermis, (2) controlled ventilation during such explorations is physiologically most desirable, and (3) irrigation of neural structures must consider acid-base and ionic parameters in order to maintain physiologic stability."}
{"id": "PMID:15693", "title": "Uterine contractility.", "content": "Many factors appear to control uterine activity in the human, either by direct action or by modulating the effects of other agents. There is no evidence to conclude that any one substance is the pre-eminent controller of physiological activity. The final common mediator of contraction evoked by stimulants is calcium and without this contractility does not occur. The action of many relaxant and contracting drugs can be ascribed to their effects on calcium binding and intracellular availability.", "contents": "Uterine contractility. Many factors appear to control uterine activity in the human, either by direct action or by modulating the effects of other agents. There is no evidence to conclude that any one substance is the pre-eminent controller of physiological activity. The final common mediator of contraction evoked by stimulants is calcium and without this contractility does not occur. The action of many relaxant and contracting drugs can be ascribed to their effects on calcium binding and intracellular availability."}
{"id": "PMID:15696", "title": "Characterization of (+/-)-methadone uptake by rat lung.", "content": "1. By use of a sensitive and specific fluorescence assay procedure it was shown that after subcutaneous administration to rats, (+/-)-methadone was concentrated in the lung. Lung to serum ratios ranging from 25 to 60 were obtained indicating that the rat lung tissue was capable of extracting (+/-)-methadone against a concentration gradient. 2. This phenomenon was investigated in vitro with rat lung slices incubated in Krebs-Ringer phosphate buffer (pH 7.4). The uptake was expressed in terms of tissue to medium concentration ratios (T/M ratio). 3. The principal observations were: (i) Studies on the time-course of the uptake showed that the T/M ratios of (+/-)-methadone increased rapidly during the first 60 min of incubation and then more slowly, with a plateau occurring at 180 min; (ii) The T/M ratio of (+/-)-methadone progressively increased from 9.5 to 17 as the pH of the incubation medium was varied from 6.2 to 7.5; (iii) When the concentration of (+/-)-methadone in the incubation medium was varied from 0.005 to 0.5 mM, the T/M ratio decreased rapidly suggesting self-saturation of the transport process. Beyond the medium concentration of 0.5 mM, the T/M ratio declined very slowly. 4. These results suggested that at low concentrations, (+/-)-methadone was transported predominantly by a self-saturable process while at higher concentrations it was transported by a process of simple diffusion. 5. At low concentrations (0.01 mM) the uptake of (+)-methadone was higher than that of (-)-isomer indicating stereo-specificity of the uptake process. The uptake of (+/-)-methadone at low concentration (0.01 mM) was significantly inhibited by low temperature, lack of O2, lack of glucose, lack of Na+ in the incubation medium, and by exposure of the tissue to high temperature (approximately 100 degrees C). The uptake was also inhibited by relatively high concentration of iodoacetate (1.0 mM) and of naloxone (1.0 mM). 6. Kinetic analysis of data showed that the diffusion constant for (+/-)-methadone was 5.0 (h-1) and the Vmax of the active transport process was 6.5 micronmol g-1h-1.", "contents": "Characterization of (+/-)-methadone uptake by rat lung. 1. By use of a sensitive and specific fluorescence assay procedure it was shown that after subcutaneous administration to rats, (+/-)-methadone was concentrated in the lung. Lung to serum ratios ranging from 25 to 60 were obtained indicating that the rat lung tissue was capable of extracting (+/-)-methadone against a concentration gradient. 2. This phenomenon was investigated in vitro with rat lung slices incubated in Krebs-Ringer phosphate buffer (pH 7.4). The uptake was expressed in terms of tissue to medium concentration ratios (T/M ratio). 3. The principal observations were: (i) Studies on the time-course of the uptake showed that the T/M ratios of (+/-)-methadone increased rapidly during the first 60 min of incubation and then more slowly, with a plateau occurring at 180 min; (ii) The T/M ratio of (+/-)-methadone progressively increased from 9.5 to 17 as the pH of the incubation medium was varied from 6.2 to 7.5; (iii) When the concentration of (+/-)-methadone in the incubation medium was varied from 0.005 to 0.5 mM, the T/M ratio decreased rapidly suggesting self-saturation of the transport process. Beyond the medium concentration of 0.5 mM, the T/M ratio declined very slowly. 4. These results suggested that at low concentrations, (+/-)-methadone was transported predominantly by a self-saturable process while at higher concentrations it was transported by a process of simple diffusion. 5. At low concentrations (0.01 mM) the uptake of (+)-methadone was higher than that of (-)-isomer indicating stereo-specificity of the uptake process. The uptake of (+/-)-methadone at low concentration (0.01 mM) was significantly inhibited by low temperature, lack of O2, lack of glucose, lack of Na+ in the incubation medium, and by exposure of the tissue to high temperature (approximately 100 degrees C). The uptake was also inhibited by relatively high concentration of iodoacetate (1.0 mM) and of naloxone (1.0 mM). 6. Kinetic analysis of data showed that the diffusion constant for (+/-)-methadone was 5.0 (h-1) and the Vmax of the active transport process was 6.5 micronmol g-1h-1."}
{"id": "PMID:15697", "title": "The pharmacology of adrenergic neuronal responses in the cerebral cortex: evidence for excitatory alpha- and inhibitory beta-receptors.", "content": "1. The technique of microelectrophoresis was used to compare the actions of a range of adrenoceptor agonists on single cortical neurones in the rat anaesthetized with halothane. 2. Phenylephrine and methoxamine were exclusively excitatory, whereas salbutamol was entirely depressant. Noradrenaline and isoprenaline could evoke both excitatory and depressant responses. Lower doses of isoprenaline usually evoked depressions, whereas higher doses, on the same cell, evoked excitatory responses. 3. The alpha-adrenoceptor blocking agents, phentolamine and phenoxybenzamine, reversibly antagonized excitatory responses to adrenoceptor agonists, without affecting depressant responses to adrenoceptor agonists or excitatory responses to acetylcholine. 4. The beta-adrenoceptor blocking agents, propranolol and sotalol, reversibly antagonized both depressant and excitatory responses to adrenoceptor agonists, without affecting responses to acetylcholine. When the effect of sotalol on excitatory and depressant responses to adrenoceptor agonists was compared on the same cell, the depressant responses could be selectively antagonized, without affecting the excitatory responses. 5. It is concluded that (a) responses of cortical neurones to adrenoceptor agonists are mediated by both alpha- and beta-receptors; (b) these alpha- and beta-receptors give rise to opposite effects: the alpha-receptors being excitatory and the beta-receptors being inhibitory; and (c) responses of many neurones reflect the presence of both types of receptor.", "contents": "The pharmacology of adrenergic neuronal responses in the cerebral cortex: evidence for excitatory alpha- and inhibitory beta-receptors. 1. The technique of microelectrophoresis was used to compare the actions of a range of adrenoceptor agonists on single cortical neurones in the rat anaesthetized with halothane. 2. Phenylephrine and methoxamine were exclusively excitatory, whereas salbutamol was entirely depressant. Noradrenaline and isoprenaline could evoke both excitatory and depressant responses. Lower doses of isoprenaline usually evoked depressions, whereas higher doses, on the same cell, evoked excitatory responses. 3. The alpha-adrenoceptor blocking agents, phentolamine and phenoxybenzamine, reversibly antagonized excitatory responses to adrenoceptor agonists, without affecting depressant responses to adrenoceptor agonists or excitatory responses to acetylcholine. 4. The beta-adrenoceptor blocking agents, propranolol and sotalol, reversibly antagonized both depressant and excitatory responses to adrenoceptor agonists, without affecting responses to acetylcholine. When the effect of sotalol on excitatory and depressant responses to adrenoceptor agonists was compared on the same cell, the depressant responses could be selectively antagonized, without affecting the excitatory responses. 5. It is concluded that (a) responses of cortical neurones to adrenoceptor agonists are mediated by both alpha- and beta-receptors; (b) these alpha- and beta-receptors give rise to opposite effects: the alpha-receptors being excitatory and the beta-receptors being inhibitory; and (c) responses of many neurones reflect the presence of both types of receptor."}
{"id": "PMID:15698", "title": "The effects of labetalol (AH 5158) on adrenergic transmission in the cat spleen.", "content": "1. The competitive alpha- and beta-adrenoceptor blocking agent labetalol, in concentrations up to 10(-4) M, produced dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 and 30 Hz. 2. At concentrations above 10(-4) M labetol produced a pronounced decrease in transmitter overflow. 3. Labetalol (1.5 X 10(-4) M) increased the recovery of 3H label in the venous blood following the close-arterial infusion of [3H]-(-)-noradrenaline indicating that the drug inhibits uptake of the amine. 4. Both labetalol (3.8 X 10(-5) M) and piperoxan (7.4 X 10(-6) M) produced parallel shifts to the right of the dose-response curves to noradrenaline and oxymetazoline in isolated strips of cat splenic capsule. In this preparation both drugs acted as competitive postsynaptic alpha-adrenoceptor blocking agents. 5. Labetalol (3.3 X 10(-5) M) increased the transmitter overflow following stimulation of the splenic nerves with 200 impulses at 10 Hz. The overflow could be further increased by subsequent addition of piperoxan (7.2 X 10(-6 M). Piperoxan (5.7 X 10(-6) M) alone produced a marked increase in transmitter overflow which could be further increased by subsequent addition of desmethylimipramine (DMI; 3.2 X 10(-5) M). Cocaine (1.5 X 10(-5) M) or DMI (5.4 X 10(-5 M) produced a small increase in transmitter overflow which was not further increased by addition of labetalol (2.8 X 10(-5) M). 6. Labetalol produced a biphasic effect on the responses of the isolated blood perfused spleen of the cat to nerve stimulation. With low doses (up to 10(-4) M) vascular responses were potentiated and with high doses (greater than 10(-4) M) inhibited. The potentiation was related to uptake blockade and the inhibition to decreased transmitter overflow and postsynaptic alpha-adrenoceptor blockade. 7. Labetalol appears to act as a postsynaptic alpha-adrenoceptor antagonist in the isolated blood perfused spleen of the cat with little effect on presynaptic alpha-adrenoceptors. The moderate elevation of transmitter overflow by the drug is related to the inhibitory effect of the drug on neuronal uptake rather than on presynaptic alpha-adrenoceptors.", "contents": "The effects of labetalol (AH 5158) on adrenergic transmission in the cat spleen. 1. The competitive alpha- and beta-adrenoceptor blocking agent labetalol, in concentrations up to 10(-4) M, produced dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 and 30 Hz. 2. At concentrations above 10(-4) M labetol produced a pronounced decrease in transmitter overflow. 3. Labetalol (1.5 X 10(-4) M) increased the recovery of 3H label in the venous blood following the close-arterial infusion of [3H]-(-)-noradrenaline indicating that the drug inhibits uptake of the amine. 4. Both labetalol (3.8 X 10(-5) M) and piperoxan (7.4 X 10(-6) M) produced parallel shifts to the right of the dose-response curves to noradrenaline and oxymetazoline in isolated strips of cat splenic capsule. In this preparation both drugs acted as competitive postsynaptic alpha-adrenoceptor blocking agents. 5. Labetalol (3.3 X 10(-5) M) increased the transmitter overflow following stimulation of the splenic nerves with 200 impulses at 10 Hz. The overflow could be further increased by subsequent addition of piperoxan (7.2 X 10(-6 M). Piperoxan (5.7 X 10(-6) M) alone produced a marked increase in transmitter overflow which could be further increased by subsequent addition of desmethylimipramine (DMI; 3.2 X 10(-5) M). Cocaine (1.5 X 10(-5) M) or DMI (5.4 X 10(-5 M) produced a small increase in transmitter overflow which was not further increased by addition of labetalol (2.8 X 10(-5) M). 6. Labetalol produced a biphasic effect on the responses of the isolated blood perfused spleen of the cat to nerve stimulation. With low doses (up to 10(-4) M) vascular responses were potentiated and with high doses (greater than 10(-4) M) inhibited. The potentiation was related to uptake blockade and the inhibition to decreased transmitter overflow and postsynaptic alpha-adrenoceptor blockade. 7. Labetalol appears to act as a postsynaptic alpha-adrenoceptor antagonist in the isolated blood perfused spleen of the cat with little effect on presynaptic alpha-adrenoceptors. The moderate elevation of transmitter overflow by the drug is related to the inhibitory effect of the drug on neuronal uptake rather than on presynaptic alpha-adrenoceptors."}
{"id": "PMID:15699", "title": "Drug prescription in Iceland.", "content": "Two ad hoc surveys on drugs prescribed in Reykjavik during November 1972 and November 1974 were made. After the first survey a publicity campaign was launched and doctors were encouraged to change their prescribing habits; only minor changes in docotors' prescribing habits were noticed, although it is realised that this type of programme will require a longer period to prove its effectiveness. The surveys showed that benzodiazepines are more widely prescribed than chlorodiazepoxide. Doctors have been warned of the probable addictive effect of benzodiazepines (Grimsson et al., 1974). Drug addicts who used to go from one surgery to another have now been identified and they can only receive drugs on prescription from their own family doctor or his deputy.", "contents": "Drug prescription in Iceland. Two ad hoc surveys on drugs prescribed in Reykjavik during November 1972 and November 1974 were made. After the first survey a publicity campaign was launched and doctors were encouraged to change their prescribing habits; only minor changes in docotors' prescribing habits were noticed, although it is realised that this type of programme will require a longer period to prove its effectiveness. The surveys showed that benzodiazepines are more widely prescribed than chlorodiazepoxide. Doctors have been warned of the probable addictive effect of benzodiazepines (Grimsson et al., 1974). Drug addicts who used to go from one surgery to another have now been identified and they can only receive drugs on prescription from their own family doctor or his deputy."}
{"id": "PMID:15707", "title": "Glutamine synthetase. IX. Purification and characterization of the enzyme from sheep spleen.", "content": "Glutamine synthetase (L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2) has been purified about 550-fold from sheep spleen. The subunit weight of the enzyme is estimated to be 48 000. Sedimentation coefficient determination by density gradient centrifugation gives a value of 15.0 S. The approximate molecular weight calculated from the S value is 378500. In addition, electron micrographs of the enzyme show an \"H\" shape. Hence, the protein appears to have eight subunits. In sheep spleen, the enzyme resides chiefly in the soluble fraction of the cell. The amino acid composition of the enzyme from spleen shows similarity to that from other sources. The enzyme activity is nearly five times as high in Mg2+ as in Mn2+. ATP inhibits the enzyme; the inhibition is competitive with respect to Mg2+ATP. A number of compounds, such as D-alanine, AMP, creatine phosphate, arsenite in combination with 2,3-dimercaptopropanol, and 2-amino-4-phosphonobutyrate, also inhibit the enzyme. The inhibition by the last compound is competitive with respect to glutamate. D-Glutamate and alpha-methyl-DL-glutamate can serve as substrates in the synthesis reaction, but N-methyl-DL-glutamate cannot. On the other hand, neither D-glutamine nor N-acetyl-L-glutamine can replace L-glutamine as a substrate in the gamma-glutamyl transfer reaction of the enzyme. Inhibition of Mn2+ and ATP and its reversal by Mg2+ have been discussed as a means of regulating the enzyme activity in mammalian tissues.", "contents": "Glutamine synthetase. IX. Purification and characterization of the enzyme from sheep spleen. Glutamine synthetase (L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2) has been purified about 550-fold from sheep spleen. The subunit weight of the enzyme is estimated to be 48 000. Sedimentation coefficient determination by density gradient centrifugation gives a value of 15.0 S. The approximate molecular weight calculated from the S value is 378500. In addition, electron micrographs of the enzyme show an \"H\" shape. Hence, the protein appears to have eight subunits. In sheep spleen, the enzyme resides chiefly in the soluble fraction of the cell. The amino acid composition of the enzyme from spleen shows similarity to that from other sources. The enzyme activity is nearly five times as high in Mg2+ as in Mn2+. ATP inhibits the enzyme; the inhibition is competitive with respect to Mg2+ATP. A number of compounds, such as D-alanine, AMP, creatine phosphate, arsenite in combination with 2,3-dimercaptopropanol, and 2-amino-4-phosphonobutyrate, also inhibit the enzyme. The inhibition by the last compound is competitive with respect to glutamate. D-Glutamate and alpha-methyl-DL-glutamate can serve as substrates in the synthesis reaction, but N-methyl-DL-glutamate cannot. On the other hand, neither D-glutamine nor N-acetyl-L-glutamine can replace L-glutamine as a substrate in the gamma-glutamyl transfer reaction of the enzyme. Inhibition of Mn2+ and ATP and its reversal by Mg2+ have been discussed as a means of regulating the enzyme activity in mammalian tissues."}
{"id": "PMID:15708", "title": "Factors affecting inosinate synthesis and inosine triphosphate accumulation in human erythrocytes.", "content": "Measurements of rates of inosinate synthesis from radioactive hypoxanthine by human erythrocytes show a large degree of individual variation. Rates of inosinate synthesis also vary with the pH and phosphate concentration of the incubation medium. This may be due to changes in the rate of phosphoribosyl pyrophosphate synthesis, and the stimulatory effect of phosphate on this process seems to be more important than the inhibitory effect of 2,3-diphodphoglycerate. The rate of inosinate synthesis, and especially the extent of accumulation of inosine triphosphate, increase disproportionately with time of incubation up to at least 24 h. Storage of erythrocytes also tends to increase inosinate synthesis and inosine triphosphate accumulation.", "contents": "Factors affecting inosinate synthesis and inosine triphosphate accumulation in human erythrocytes. Measurements of rates of inosinate synthesis from radioactive hypoxanthine by human erythrocytes show a large degree of individual variation. Rates of inosinate synthesis also vary with the pH and phosphate concentration of the incubation medium. This may be due to changes in the rate of phosphoribosyl pyrophosphate synthesis, and the stimulatory effect of phosphate on this process seems to be more important than the inhibitory effect of 2,3-diphodphoglycerate. The rate of inosinate synthesis, and especially the extent of accumulation of inosine triphosphate, increase disproportionately with time of incubation up to at least 24 h. Storage of erythrocytes also tends to increase inosinate synthesis and inosine triphosphate accumulation."}
{"id": "PMID:15709", "title": "Synthesis of soluble dextran-hemoglobin complexes of different molecular sizes.", "content": "Experimental conditions were defined that determined the synthesis of dextran-hemoglobin complexes through the alklation of hemoglobin by N-bromoacetylaminoethylaminodextran. Using appropriate concentrations of the two reactants, over 90% yield of dextran-hemoglobin was obtained for dextrans of average molecular weight of 200 000 110000, 70000, 400000, and 20000. Extensive viscosity increase due to crosslinking could be avoided, and a large molar excess of dextran over hemoglobin made unnecessary, under the optimal conditions.", "contents": "Synthesis of soluble dextran-hemoglobin complexes of different molecular sizes. Experimental conditions were defined that determined the synthesis of dextran-hemoglobin complexes through the alklation of hemoglobin by N-bromoacetylaminoethylaminodextran. Using appropriate concentrations of the two reactants, over 90% yield of dextran-hemoglobin was obtained for dextrans of average molecular weight of 200 000 110000, 70000, 400000, and 20000. Extensive viscosity increase due to crosslinking could be avoided, and a large molar excess of dextran over hemoglobin made unnecessary, under the optimal conditions."}
{"id": "PMID:15710", "title": "The chemical and kinetic consequences of the modification of papain by N-bromosuccinimide.", "content": "Nonactivated papain was treated with N-bromosuccinimide at pH 4.75. The N-bromosuccinimide-modified enzyme was characterized by (1) the change in absorbance at 280 nm, (2) amino acid analysis, (3) separate chemical determinations of tryptophan and tyrosine (4) difference spectroscopy, and (5) an N-terminal residue determination. It is concluded that N-bromosuccinimide in sevenfold molar excess oxidizes one tryptophan and two to three tyrosine residues per molecule of nonactivated papain, without causing peptide chain cleavage. Kinetic studies with several substrates and competitive peptide inhibitors were performed at pH6 using the N-bromosuccinimide-modified papain. In addition, the kinetics of the modified enzyme with the substrate alpha-N-benzoyl-L-arginine ethl ester were studied in the region of pH 3.5-9.0. All substrates (and inhibitors) test, with the exception of alpha-N-benzyoyl-L-arginine p-nitroanilide, displayed approximately a two fold decrease in both kcat and Km (or Ki), relative to the native enzyme. It is concluded that the key tryptophan residue which is probably Trp-177.", "contents": "The chemical and kinetic consequences of the modification of papain by N-bromosuccinimide. Nonactivated papain was treated with N-bromosuccinimide at pH 4.75. The N-bromosuccinimide-modified enzyme was characterized by (1) the change in absorbance at 280 nm, (2) amino acid analysis, (3) separate chemical determinations of tryptophan and tyrosine (4) difference spectroscopy, and (5) an N-terminal residue determination. It is concluded that N-bromosuccinimide in sevenfold molar excess oxidizes one tryptophan and two to three tyrosine residues per molecule of nonactivated papain, without causing peptide chain cleavage. Kinetic studies with several substrates and competitive peptide inhibitors were performed at pH6 using the N-bromosuccinimide-modified papain. In addition, the kinetics of the modified enzyme with the substrate alpha-N-benzoyl-L-arginine ethl ester were studied in the region of pH 3.5-9.0. All substrates (and inhibitors) test, with the exception of alpha-N-benzyoyl-L-arginine p-nitroanilide, displayed approximately a two fold decrease in both kcat and Km (or Ki), relative to the native enzyme. It is concluded that the key tryptophan residue which is probably Trp-177."}
{"id": "PMID:15711", "title": "Purification and properties of dihydrofolate reductase from methotrexate-sensitive and methotrexate-resistant Chinese hamster ovary cells.", "content": "We have previously described methotrexate-resistant Chinese hamster ovary cells which appear to contain normal levls of a structurally altered dihydrofolate reductase (EC 1.5.1.3) (Flintoff, W.F., Davidson, S.V., and Siminovitch, L. (1976) Somatic Cell Genet.2,245-261). By selecting for increased resistance form these class I cells, class III resistant cells were isolated which appeared to possess an increased activity of the altered enzyme. In the report, we describe the purification and several properties of the reductase from wild-type cells, two independently selected class I cells, and class III resistant cell. The reductases from wild-type and resistant cells had similar specific activities using folate and dihydrofolate as substrates, and similar molecular weights as determined by sodium dodecyl sulfate gel electrophoresis. The mutant enzymes, however, were about six- to eight-fold more resistant to inhibition by methotrexate than the wild-type enzyme, suggesting a decreased affinity of the mutant reductases to methotrexate-binding. Small differences between various enzymes were also seen in other physicochemical properties such as pH optima and Km values for folate, and in their heat stabilities, which suggest that different structural alterations may lead to the same mutant phenotype. As expected from earlier studies with crude extracts, class III cells did produce a higher (about 10-fold) yield of the reductase than the class I or wild-type cells.", "contents": "Purification and properties of dihydrofolate reductase from methotrexate-sensitive and methotrexate-resistant Chinese hamster ovary cells. We have previously described methotrexate-resistant Chinese hamster ovary cells which appear to contain normal levls of a structurally altered dihydrofolate reductase (EC 1.5.1.3) (Flintoff, W.F., Davidson, S.V., and Siminovitch, L. (1976) Somatic Cell Genet.2,245-261). By selecting for increased resistance form these class I cells, class III resistant cells were isolated which appeared to possess an increased activity of the altered enzyme. In the report, we describe the purification and several properties of the reductase from wild-type cells, two independently selected class I cells, and class III resistant cell. The reductases from wild-type and resistant cells had similar specific activities using folate and dihydrofolate as substrates, and similar molecular weights as determined by sodium dodecyl sulfate gel electrophoresis. The mutant enzymes, however, were about six- to eight-fold more resistant to inhibition by methotrexate than the wild-type enzyme, suggesting a decreased affinity of the mutant reductases to methotrexate-binding. Small differences between various enzymes were also seen in other physicochemical properties such as pH optima and Km values for folate, and in their heat stabilities, which suggest that different structural alterations may lead to the same mutant phenotype. As expected from earlier studies with crude extracts, class III cells did produce a higher (about 10-fold) yield of the reductase than the class I or wild-type cells."}
{"id": "PMID:15712", "title": "Reversibility of the ampicillin-and nitrite-induced inactivation of beta-lactamase I.", "content": "beta-Lactamase I was isolated from Bacillus cereus 569/H. Treatment with ampicillin in the presence of sodium nitrite at pH 4 or 5 resulted in the inactivation of the enzyme presumably by modification of a carboxyl group in the active site. However, this inactivation was rapidly, reversible at neutral pH and the available evidence points to the participation of a second carboxyl group which is involved in the reactivation process.", "contents": "Reversibility of the ampicillin-and nitrite-induced inactivation of beta-lactamase I. beta-Lactamase I was isolated from Bacillus cereus 569/H. Treatment with ampicillin in the presence of sodium nitrite at pH 4 or 5 resulted in the inactivation of the enzyme presumably by modification of a carboxyl group in the active site. However, this inactivation was rapidly, reversible at neutral pH and the available evidence points to the participation of a second carboxyl group which is involved in the reactivation process."}
{"id": "PMID:15713", "title": "The interactions between cytochrome c and cytochrome oxidase that determine the conformation of the oxidized oxidase.", "content": "1. Cytochrome c2+ increases the rate at which cytochrome oxidase (EC 1.9.3.1) gamma max428nm) converts to its conformational isomer (gamma max 418-423 nm) but cytochrome c3+ has little effect on the conversion rate. 2. Interactions between reduced cytochrome oxidase and cytochrome c were studied in the absence of electron flow using anaerobic Sephadex columns. 3. Oxidase that is reduced by cytochrome c2+ or other reductant forms the 418-to 423-nm isomer if its last contact, before oxidation, is with cytochrome c3+. If the reduced oxidase contacts cytochrome c2+, before oxidation, the 428-nm oxidase forms.", "contents": "The interactions between cytochrome c and cytochrome oxidase that determine the conformation of the oxidized oxidase. 1. Cytochrome c2+ increases the rate at which cytochrome oxidase (EC 1.9.3.1) gamma max428nm) converts to its conformational isomer (gamma max 418-423 nm) but cytochrome c3+ has little effect on the conversion rate. 2. Interactions between reduced cytochrome oxidase and cytochrome c were studied in the absence of electron flow using anaerobic Sephadex columns. 3. Oxidase that is reduced by cytochrome c2+ or other reductant forms the 418-to 423-nm isomer if its last contact, before oxidation, is with cytochrome c3+. If the reduced oxidase contacts cytochrome c2+, before oxidation, the 428-nm oxidase forms."}
{"id": "PMID:15714", "title": "Mechanism of action of Zn2+ and Mg2+ on rat placenta alkaline phosphatase. II. Studies on membrane-bound phosphatase in tissue sections and in whole placenta.", "content": "Alkaline phosphatase (EC 3.1.3.1) bound to trophoblastic cells in rat placenta is activated by Mg2+ and inhibited by Zn2+ in the same way as is found with partially purified soluble alkaline phosphatase in the same tissue (PetitClerc, C., Delisle, M., Martel, M., Fecteau, C. & Bri\u00e8re, N. (1975) Can. J. Biochem. 53, 1089-1100). In studies done with tissue sections (6-10 micron), it is shown that alkaline phosphatase activity and labelling of active sites by orthophosphate are lost during incubation with ethanolamine at pH 9.0. Addition of Mg2+ causes total recovery of catalytic activity and active sites labelling. Zn2+ displaces and replaces at the Mg2+ binding sites. The affinity for both ions is similar, and dissociation of Zn2+ from the enzyme is a very slow process, even in the presence of Mg2+. The Zn2+-alkaline phosphatase and Mg2+-alkaline phosphatase, which only differ by the ion bound to an apparent modulator site, have the same catalytic activity at pH less than 7.0, but the Zn2+ species has little activity at alkaline pH. Phosphorylation of the enzyme by orthophosphate indicates that with both enzyme species phosphoryl intermediate does not accumulate at alkaline pH. These results suggest that with orthophosphate, the phosphorylation step is rate determining for both enzymes, and that Zn2+ affects this step to a much greater extent. It is proposed that Zn2+ and Mg2+ regulate alkaline phosphatase in rat placenta. The concentration of both ions in maternal serum and placenta suggest that such a mechanism could exist in vivo.", "contents": "Mechanism of action of Zn2+ and Mg2+ on rat placenta alkaline phosphatase. II. Studies on membrane-bound phosphatase in tissue sections and in whole placenta. Alkaline phosphatase (EC 3.1.3.1) bound to trophoblastic cells in rat placenta is activated by Mg2+ and inhibited by Zn2+ in the same way as is found with partially purified soluble alkaline phosphatase in the same tissue (PetitClerc, C., Delisle, M., Martel, M., Fecteau, C. & Bri\u00e8re, N. (1975) Can. J. Biochem. 53, 1089-1100). In studies done with tissue sections (6-10 micron), it is shown that alkaline phosphatase activity and labelling of active sites by orthophosphate are lost during incubation with ethanolamine at pH 9.0. Addition of Mg2+ causes total recovery of catalytic activity and active sites labelling. Zn2+ displaces and replaces at the Mg2+ binding sites. The affinity for both ions is similar, and dissociation of Zn2+ from the enzyme is a very slow process, even in the presence of Mg2+. The Zn2+-alkaline phosphatase and Mg2+-alkaline phosphatase, which only differ by the ion bound to an apparent modulator site, have the same catalytic activity at pH less than 7.0, but the Zn2+ species has little activity at alkaline pH. Phosphorylation of the enzyme by orthophosphate indicates that with both enzyme species phosphoryl intermediate does not accumulate at alkaline pH. These results suggest that with orthophosphate, the phosphorylation step is rate determining for both enzymes, and that Zn2+ affects this step to a much greater extent. It is proposed that Zn2+ and Mg2+ regulate alkaline phosphatase in rat placenta. The concentration of both ions in maternal serum and placenta suggest that such a mechanism could exist in vivo."}
{"id": "PMID:15715", "title": "The subcellular distribution of poly-A-degrading activity in mouse kidney.", "content": "Most (95%) of the poly-A-degrading activity of the mouse kidney was found in the cytoplasmic fraction and only 5% was found in the nuclear fraction; 43% of the poly-A-degrading activity of the cytoplasm was found in the mitochondria, 22% in the microsomes, and 30% in the soluble fraction. Differences in activity and specificity indicate that poly A is degraded in the nucleus by enzymes that are separate and distinct from the enzymes in the cytoplasm that degrade poly A. The nuclear poly-A-degrading activity can be separated into an endonuclease with a general specificity and exonuclease, similar to one found in Ehrlich ascites tumor cells, which shows some specificity for poly A.", "contents": "The subcellular distribution of poly-A-degrading activity in mouse kidney. Most (95%) of the poly-A-degrading activity of the mouse kidney was found in the cytoplasmic fraction and only 5% was found in the nuclear fraction; 43% of the poly-A-degrading activity of the cytoplasm was found in the mitochondria, 22% in the microsomes, and 30% in the soluble fraction. Differences in activity and specificity indicate that poly A is degraded in the nucleus by enzymes that are separate and distinct from the enzymes in the cytoplasm that degrade poly A. The nuclear poly-A-degrading activity can be separated into an endonuclease with a general specificity and exonuclease, similar to one found in Ehrlich ascites tumor cells, which shows some specificity for poly A."}
{"id": "PMID:15716", "title": "The effects of light and tyrosinase during sclerotium development in Sclerotium rolfsii Sacc.", "content": "Some effects of light on morphogenesis in Sclerotium rolfsii Sacc. were studied. Physiological competence to visible light developed during the first 120 h after inoculation, with an optimum sensitivity phase between 84 and 96 h that coincided with the leading hyphae reaching the edge of the Petri dish. Although sclerotial initials were produced in dark-grown cultures, light was necessary for the continuation of the developmental and maturation phases of sclerotial morphogenesis. Tyrosinase activity (o-diphenol: oxygen oxidoreductase, EC 1.10.3.1) was detected during sclerotial formation and the pH and temperature optima for his polyphenol oxidase in vitro were about 6.0 and 45 degrees C respectively. The enzyme was inhibited by cysteine. Similar activity levels of tyrosinase were obtained in blue and \"white\" light-grown cultures but in red light activity was comparable with that of dark-grown cultures. Laccase activity was not detected at any stage of development.", "contents": "The effects of light and tyrosinase during sclerotium development in Sclerotium rolfsii Sacc. Some effects of light on morphogenesis in Sclerotium rolfsii Sacc. were studied. Physiological competence to visible light developed during the first 120 h after inoculation, with an optimum sensitivity phase between 84 and 96 h that coincided with the leading hyphae reaching the edge of the Petri dish. Although sclerotial initials were produced in dark-grown cultures, light was necessary for the continuation of the developmental and maturation phases of sclerotial morphogenesis. Tyrosinase activity (o-diphenol: oxygen oxidoreductase, EC 1.10.3.1) was detected during sclerotial formation and the pH and temperature optima for his polyphenol oxidase in vitro were about 6.0 and 45 degrees C respectively. The enzyme was inhibited by cysteine. Similar activity levels of tyrosinase were obtained in blue and \"white\" light-grown cultures but in red light activity was comparable with that of dark-grown cultures. Laccase activity was not detected at any stage of development."}
{"id": "PMID:15717", "title": "Stannous and cuprous ion oxidation by Thiobacillus ferrooxidans.", "content": "Oxidation of stannous chloride by Thiobacillus ferrooxidans was studied manometrically. At low stannous ion concentrations, initial oxidation rate was proportional to concentration. Optimum pH for oxidation was 2.3 optimum temperature was 37-40 degrees C. Spectrophotometry showed reduction of cytochromes in suspensions of whole cells on addition of ferrous, stannous, or cuprous salts. Cytochrome c reductase activity in cell-free extracts was assayed with ferrous, stannous, or cuprous ions as electron donors. It appears unlikely that an essential non-biological reaction, the reduction of ferric ions by stannous or cuprous ions, is involved. Growth of T. ferrooxidans was not obtained with either stannous chloride or stannous sulphate as sole energy source.", "contents": "Stannous and cuprous ion oxidation by Thiobacillus ferrooxidans. Oxidation of stannous chloride by Thiobacillus ferrooxidans was studied manometrically. At low stannous ion concentrations, initial oxidation rate was proportional to concentration. Optimum pH for oxidation was 2.3 optimum temperature was 37-40 degrees C. Spectrophotometry showed reduction of cytochromes in suspensions of whole cells on addition of ferrous, stannous, or cuprous salts. Cytochrome c reductase activity in cell-free extracts was assayed with ferrous, stannous, or cuprous ions as electron donors. It appears unlikely that an essential non-biological reaction, the reduction of ferric ions by stannous or cuprous ions, is involved. Growth of T. ferrooxidans was not obtained with either stannous chloride or stannous sulphate as sole energy source."}
{"id": "PMID:15719", "title": "Prolactin binding in ovariectomy-responsive and ovariectomy-nonresponsive rat mammary carcinoma.", "content": "Growth of the transplantable mammary tumor, MTW9, in W/Fu rats is greatly enhanced by elevated serum prolactin concentrations. This report compares the prolactin binding to tumor membranes in two mammary tumor strains derived from MTW9. Maximum binding to membranes of both tumors occurred at pH 7.6 after incubation for 30 hr at 4 degrees. The binding was inhibited only by polypeptide hormones that possess lactogenic activity. MTW9-P, an ovariectomy-responsive tumor developed in rats maintained on daily perphenazine injections, had 4-fold-higher prolactin binding than had MTW9MtT, an ovariectomy-nonresponsive tumor developed in rats bearing the mammosomatotropic pituitary tumor, MtTW10. Withdrawal of perphenazine from rats bearing MTW9-P caused a fall to normal of plasma prolactin, no tumor regression, and no significant change in prolactin binding. In contrast, resection of MtT resulted in tumor regression, a fall to normal of serum prolactin, and a nearly 3-fold increase in prolactin binding. Scatchard plots of prolactin binding data yield an apparent affinity constant, Ka, of 1.2 X 109 liters/mole for both tumors. The 4-fold-higher prolactin binding in the ovariectomy responsive variant suggests a positive correlation between ovariectomy response and the number of membrane prolactin-binding sites. No correlation between prolactin sensitivity and prolacting binding is apparent.", "contents": "Prolactin binding in ovariectomy-responsive and ovariectomy-nonresponsive rat mammary carcinoma. Growth of the transplantable mammary tumor, MTW9, in W/Fu rats is greatly enhanced by elevated serum prolactin concentrations. This report compares the prolactin binding to tumor membranes in two mammary tumor strains derived from MTW9. Maximum binding to membranes of both tumors occurred at pH 7.6 after incubation for 30 hr at 4 degrees. The binding was inhibited only by polypeptide hormones that possess lactogenic activity. MTW9-P, an ovariectomy-responsive tumor developed in rats maintained on daily perphenazine injections, had 4-fold-higher prolactin binding than had MTW9MtT, an ovariectomy-nonresponsive tumor developed in rats bearing the mammosomatotropic pituitary tumor, MtTW10. Withdrawal of perphenazine from rats bearing MTW9-P caused a fall to normal of plasma prolactin, no tumor regression, and no significant change in prolactin binding. In contrast, resection of MtT resulted in tumor regression, a fall to normal of serum prolactin, and a nearly 3-fold increase in prolactin binding. Scatchard plots of prolactin binding data yield an apparent affinity constant, Ka, of 1.2 X 109 liters/mole for both tumors. The 4-fold-higher prolactin binding in the ovariectomy responsive variant suggests a positive correlation between ovariectomy response and the number of membrane prolactin-binding sites. No correlation between prolactin sensitivity and prolacting binding is apparent."}
{"id": "PMID:15720", "title": "Transglutaminase activity in normal and transformed cells.", "content": "Transglutaminase activity was determined in normal and transformed paired cell systems. Reduced enzyme activity was found in virus-transformed human and hamster cells and in chemically transformed mouse cells relative to normal counterparts. Most of the enzyme activity was localized in the particulate fraction sedimenting at 105,000 X g. Enzyme activity was highest when normal cell populations were in an essentially nonmitotic state. Protein capable of incorporating putrescine was present in normal and transformed human cells, although the rate of incorporation was lower in the latter. The putrescine acceptor in the normal cell paralleled enzyme activity and enzyme distribution. Trypsin (5 microng/ml) treatment of the normal cell resulted in a 3-fold increase in enzyme activity, which occurred independently of protein synthesis.", "contents": "Transglutaminase activity in normal and transformed cells. Transglutaminase activity was determined in normal and transformed paired cell systems. Reduced enzyme activity was found in virus-transformed human and hamster cells and in chemically transformed mouse cells relative to normal counterparts. Most of the enzyme activity was localized in the particulate fraction sedimenting at 105,000 X g. Enzyme activity was highest when normal cell populations were in an essentially nonmitotic state. Protein capable of incorporating putrescine was present in normal and transformed human cells, although the rate of incorporation was lower in the latter. The putrescine acceptor in the normal cell paralleled enzyme activity and enzyme distribution. Trypsin (5 microng/ml) treatment of the normal cell resulted in a 3-fold increase in enzyme activity, which occurred independently of protein synthesis."}
{"id": "PMID:15721", "title": "Interactions between \"fever\" proteins and normal serum proteins in febrile cancer patients.", "content": "When analyzed by cationic discontinuous electrophoresis in urea-containing polyacrylamide gels, plasma or serum from febrile individuals contains trace quanitites of five protein bands that are not recognizable in the blood of normal individuals. These proteins appear and disappear in parallel in sequential samples. Cerebrospinal fluid from febrile and nonfebrile individuals contains a protein band that is electrophoretically identical with only one of these proteins. Since the trace proteins migrate, in urea-containing polyacrylamide gel electrophoresis, as if they has molecular size of less than or equal to30,000 daltons, their absence from cerebrospinal fluid implies the existence, in vivo, of interactions between them and other serum proteins. Under nondissociating conditions, four of the bands appear to circulate in physical interaction with one another. In molecular sieve chromatography at neutral pH in lipid-free sera, the trace proteins have an approximate molecular size of 165,000 daltons; in lipemic sera they have a molecular weight of larger than or equal to200,000 daltons. Their behavior in gel filtration and in ion-exchange chromatography excludes extensive interaction with any of the following: immunoglobulin M, immunoglobulin G, alpha2-macroglobulin, haptoglobin, and albumin. Interactions between these and other serum proteins are reduced by high concentrations of urea and by low PH. The mechanisms responsible for the observed protein-protein associations would appear to include electrostatic attraction, hydrogen bonding, and weak hydrophobic interaction.", "contents": "Interactions between \"fever\" proteins and normal serum proteins in febrile cancer patients. When analyzed by cationic discontinuous electrophoresis in urea-containing polyacrylamide gels, plasma or serum from febrile individuals contains trace quanitites of five protein bands that are not recognizable in the blood of normal individuals. These proteins appear and disappear in parallel in sequential samples. Cerebrospinal fluid from febrile and nonfebrile individuals contains a protein band that is electrophoretically identical with only one of these proteins. Since the trace proteins migrate, in urea-containing polyacrylamide gel electrophoresis, as if they has molecular size of less than or equal to30,000 daltons, their absence from cerebrospinal fluid implies the existence, in vivo, of interactions between them and other serum proteins. Under nondissociating conditions, four of the bands appear to circulate in physical interaction with one another. In molecular sieve chromatography at neutral pH in lipid-free sera, the trace proteins have an approximate molecular size of 165,000 daltons; in lipemic sera they have a molecular weight of larger than or equal to200,000 daltons. Their behavior in gel filtration and in ion-exchange chromatography excludes extensive interaction with any of the following: immunoglobulin M, immunoglobulin G, alpha2-macroglobulin, haptoglobin, and albumin. Interactions between these and other serum proteins are reduced by high concentrations of urea and by low PH. The mechanisms responsible for the observed protein-protein associations would appear to include electrostatic attraction, hydrogen bonding, and weak hydrophobic interaction."}
{"id": "PMID:15722", "title": "Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore.", "content": "Cultured human neuroblastoma cell lines were assayed for biochemical characteristics of neuonal function. Cell lines studied included LA-N-1, LA-N-2, IMR-32, SK-N-SH, and SK-N-MC. Veratridine-dependent uptake of 22Na+ implied the presence of the action potential Na+ ionophore in LA-N-1, LA-N-2, IMR-32, and SK-N-SH. The time course of 22Na+ uptake and inhibition of uptake by tetrodotoxin supported this. SK-N-MC had no veratridine-dependent 22Na+ uptake. Tyrosine hydroxylase (EC 1.14.10.), glutamic acid decarboxylase (EC 4.1.1.15), and acetylcholine contents in neuroblastoma cells were compared to those in brain. LA-N-1 and IMR-32 contained 15 and 5 times as much tyrosine hydroxylase, respectively, whereas LA-N-2, SK-N-SH, and SK-N-MC contained only 0.5 to 5% of that in brain. Acetylcholine was present in -LA-N-2 in 15- to 20-fold greater quantities than in brain; other lines had only 10 to 50% of that in brain. None of the cell lines contained glutamic acid decarboxylase. Thus, continuously propogated human neuroblastoma cell lines may have the action potential Na+ ionophore and may be adrenergic (LA-N-1 and IMR-32), cholinergic (LA-N-2), or inactive (SK-N-SH and SK-N-MC). This is the first demonstration of the action potential Na+ ionophore and of acetylcholine production in human neuroblastoma cell lines.", "contents": "Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore. Cultured human neuroblastoma cell lines were assayed for biochemical characteristics of neuonal function. Cell lines studied included LA-N-1, LA-N-2, IMR-32, SK-N-SH, and SK-N-MC. Veratridine-dependent uptake of 22Na+ implied the presence of the action potential Na+ ionophore in LA-N-1, LA-N-2, IMR-32, and SK-N-SH. The time course of 22Na+ uptake and inhibition of uptake by tetrodotoxin supported this. SK-N-MC had no veratridine-dependent 22Na+ uptake. Tyrosine hydroxylase (EC 1.14.10.), glutamic acid decarboxylase (EC 4.1.1.15), and acetylcholine contents in neuroblastoma cells were compared to those in brain. LA-N-1 and IMR-32 contained 15 and 5 times as much tyrosine hydroxylase, respectively, whereas LA-N-2, SK-N-SH, and SK-N-MC contained only 0.5 to 5% of that in brain. Acetylcholine was present in -LA-N-2 in 15- to 20-fold greater quantities than in brain; other lines had only 10 to 50% of that in brain. None of the cell lines contained glutamic acid decarboxylase. Thus, continuously propogated human neuroblastoma cell lines may have the action potential Na+ ionophore and may be adrenergic (LA-N-1 and IMR-32), cholinergic (LA-N-2), or inactive (SK-N-SH and SK-N-MC). This is the first demonstration of the action potential Na+ ionophore and of acetylcholine production in human neuroblastoma cell lines."}
{"id": "PMID:15723", "title": "Effects of graft-versus-host reaction on inhibition of tumor growth in vivo and on tumor cytotoxicity in vitro.", "content": "In DA X Wistar F1 rats, growth of 10(4) Wistar-specific Sp 1 carcinoma cells s.c. was commonly prevented by a mild subclinical graft=versus-host reaction produced by injecting 50 X 10(6) Wistar spleen cells i.p. either concurrently with the tumor or 7 to 14 days previously, Spleen cells alone had no effect on established tumor, but their injection on Day 14 significantly reduced the recurrence rate after excision of tumor on Day 21. In vitro tests in tumor-bearing rats with graft-versus-host reactions showed increased spleen lymphocyte and serum cytotoxicity; these mechanisms may inhibit tumor growth in vivo. Because Wistar lymphocytes and Sp 1 cells are syngeneic, inhibition of tumor cannot be due to allograft rejection but is probably an effect of increased host immunoreactivity during the graft-versus-host reaction.", "contents": "Effects of graft-versus-host reaction on inhibition of tumor growth in vivo and on tumor cytotoxicity in vitro. In DA X Wistar F1 rats, growth of 10(4) Wistar-specific Sp 1 carcinoma cells s.c. was commonly prevented by a mild subclinical graft=versus-host reaction produced by injecting 50 X 10(6) Wistar spleen cells i.p. either concurrently with the tumor or 7 to 14 days previously, Spleen cells alone had no effect on established tumor, but their injection on Day 14 significantly reduced the recurrence rate after excision of tumor on Day 21. In vitro tests in tumor-bearing rats with graft-versus-host reactions showed increased spleen lymphocyte and serum cytotoxicity; these mechanisms may inhibit tumor growth in vivo. Because Wistar lymphocytes and Sp 1 cells are syngeneic, inhibition of tumor cannot be due to allograft rejection but is probably an effect of increased host immunoreactivity during the graft-versus-host reaction."}
{"id": "PMID:15724", "title": "Reactions of cellulose isothiocyanates with thiol and amino compounds.", "content": "A cellulose isothiocyanate has been prepared by treatment of cellulose with 2,4-di-isocyanatotoluene followed by hydrolysis and reaction of the resulting amine with thiophosgene. The cellulose isothiocyanate was characterized by its binding capacity with respect to [14C]-glycine, [131 I]-human serum albumin, and 2-mercaptoethanol. An analytical method for binding capacity, based on reaction with [35 S]-alpha-toluenethiol, was developed. Because of the aromatic character of the NCS group of the cellulose isothiocyanate, the covalently bonded thiol can be quantitatively liberated.", "contents": "Reactions of cellulose isothiocyanates with thiol and amino compounds. A cellulose isothiocyanate has been prepared by treatment of cellulose with 2,4-di-isocyanatotoluene followed by hydrolysis and reaction of the resulting amine with thiophosgene. The cellulose isothiocyanate was characterized by its binding capacity with respect to [14C]-glycine, [131 I]-human serum albumin, and 2-mercaptoethanol. An analytical method for binding capacity, based on reaction with [35 S]-alpha-toluenethiol, was developed. Because of the aromatic character of the NCS group of the cellulose isothiocyanate, the covalently bonded thiol can be quantitatively liberated."}
{"id": "PMID:15727", "title": "Proliferation of erythroid and granulocyte progenitors in the spleen as a function of stem cell dose.", "content": "A study of the kinetics of cellular proliferation, in the morphologically unrecongizable haemopoietic progenitor cell compartment, as a function of injected CFU-S dose has been carried out in the spleens of lethally X-irradiated mice using 3H-TdR labelling. Amplification in this proliferating cell compartment was observed to decline as CFU-S dose increased. The number of divisions in the differentiated line arising from CFU-S up to the first appearance of recognizable erythroid precursors were calculated to be 9-2, 12-5, 15 and 17 for the 2, 0-35, 0-05 and 0-007 femur equivalent doses respectively. The growth of cell populations arising from CFU-S was biphasic, with a rapid initial phase having a doubling time of about 6-3 hr, and a slow phase of doubling time around 1 day. Analysis of the rapid phase by the FLM method gave a cycle time of 5-6 hr, Recognizable labelled erythroid precursors were detected at the same time as, or just after, the change in slope of the growth curve. Significant numbers of proliferating (labelled) granulocytes only appeared in the spleens of animals receiving the higher marrow doses (2 and 0-35 femur). The erythroid to granulocyte ratio was also a decreasing function of marrow dose.", "contents": "Proliferation of erythroid and granulocyte progenitors in the spleen as a function of stem cell dose. A study of the kinetics of cellular proliferation, in the morphologically unrecongizable haemopoietic progenitor cell compartment, as a function of injected CFU-S dose has been carried out in the spleens of lethally X-irradiated mice using 3H-TdR labelling. Amplification in this proliferating cell compartment was observed to decline as CFU-S dose increased. The number of divisions in the differentiated line arising from CFU-S up to the first appearance of recognizable erythroid precursors were calculated to be 9-2, 12-5, 15 and 17 for the 2, 0-35, 0-05 and 0-007 femur equivalent doses respectively. The growth of cell populations arising from CFU-S was biphasic, with a rapid initial phase having a doubling time of about 6-3 hr, and a slow phase of doubling time around 1 day. Analysis of the rapid phase by the FLM method gave a cycle time of 5-6 hr, Recognizable labelled erythroid precursors were detected at the same time as, or just after, the change in slope of the growth curve. Significant numbers of proliferating (labelled) granulocytes only appeared in the spleens of animals receiving the higher marrow doses (2 and 0-35 femur). The erythroid to granulocyte ratio was also a decreasing function of marrow dose."}
{"id": "PMID:15728", "title": "The form and function of cnidarian spirocysts. 3. Ultrastructure of the thread and the function of spirocysts.", "content": "Unlike most nematocysts, undischarged spirocyst threads bear hollow tubules rather than spines. The undischarged tubules are interconnected in hexagonal arrays and appear to be arranged in bundles along the length of the thread. Although the wall of the thread is folded in length and width, the tubules are not. Upon discharge and contact with sea water, the tubules solubilize and adhere to various substrates and prey. Traction between such objects and the everting thread causes the tubules to spin out into a web or meshwork of fine microfibrillae. Lack of contact of the everting thread with objects results in the tubules forming small droplets of partially solubilized material, some of which appear to be arranged in a helical pattern around the thread. The web or meshwork formed by the solubilized tubules in contact with various substrates probably serves to increase significantly the surface area and adhesive properties of the everted spirocyst thread.", "contents": "The form and function of cnidarian spirocysts. 3. Ultrastructure of the thread and the function of spirocysts. Unlike most nematocysts, undischarged spirocyst threads bear hollow tubules rather than spines. The undischarged tubules are interconnected in hexagonal arrays and appear to be arranged in bundles along the length of the thread. Although the wall of the thread is folded in length and width, the tubules are not. Upon discharge and contact with sea water, the tubules solubilize and adhere to various substrates and prey. Traction between such objects and the everting thread causes the tubules to spin out into a web or meshwork of fine microfibrillae. Lack of contact of the everting thread with objects results in the tubules forming small droplets of partially solubilized material, some of which appear to be arranged in a helical pattern around the thread. The web or meshwork formed by the solubilized tubules in contact with various substrates probably serves to increase significantly the surface area and adhesive properties of the everted spirocyst thread."}
{"id": "PMID:15730", "title": "Importance of glycerol and fatty acid residues on the ionic properties of phosphatidylglycerols at the air-water interface.", "content": "Ionic properties of didodecanoylphosphatidylglycerol (C12PG), didodecanolyphosphatidyl-l'-propanol (C12PP), di-(12-methyl, 13-methyl)-pentadecanoylphosphatidylglycerols (C15PG) and dihexadecanoylphosphatidylglycerol (C16PG) have been studied at the air-water interface using titration experiments at constant ionic strength and film expansion experiments at constant pH, with Li+, Na+, K+ and Cs+ in the subphase. For each lipid, the apparent pK in the surface is strongly dependent on the subphase salt concentration and differs from expected intrinsic pK in the bulk. Discrimination between alkaline cations is observed. These results can be accounted for by strong surface potentials, which are satisfactorily calculated by using the Gouy and Chapman theory of the diffuse double layer. The comparison of C12PP and PG expansion data shows the importance of the glycerol residue of PG ionic properties, favouring penetration of cations in the films. Lipids in the liquid-crystalline state, such as C12-and C15PG, do not interact with alkaline cations as does C16PG in the gel phase. In particular, film condensations bring about a clear-cut discrimination between Na+ and K+. Results are discussed with regard to cation penetration and the structure of water at the interface. The importance on membrane functions of these strong surface potentials generated by PG monolayers is suggested.", "contents": "Importance of glycerol and fatty acid residues on the ionic properties of phosphatidylglycerols at the air-water interface. Ionic properties of didodecanoylphosphatidylglycerol (C12PG), didodecanolyphosphatidyl-l'-propanol (C12PP), di-(12-methyl, 13-methyl)-pentadecanoylphosphatidylglycerols (C15PG) and dihexadecanoylphosphatidylglycerol (C16PG) have been studied at the air-water interface using titration experiments at constant ionic strength and film expansion experiments at constant pH, with Li+, Na+, K+ and Cs+ in the subphase. For each lipid, the apparent pK in the surface is strongly dependent on the subphase salt concentration and differs from expected intrinsic pK in the bulk. Discrimination between alkaline cations is observed. These results can be accounted for by strong surface potentials, which are satisfactorily calculated by using the Gouy and Chapman theory of the diffuse double layer. The comparison of C12PP and PG expansion data shows the importance of the glycerol residue of PG ionic properties, favouring penetration of cations in the films. Lipids in the liquid-crystalline state, such as C12-and C15PG, do not interact with alkaline cations as does C16PG in the gel phase. In particular, film condensations bring about a clear-cut discrimination between Na+ and K+. Results are discussed with regard to cation penetration and the structure of water at the interface. The importance on membrane functions of these strong surface potentials generated by PG monolayers is suggested."}
{"id": "PMID:15731", "title": "[Increase in the oxygen available to the cerebral cortex after the administration of carbonic anhydrase inhibitors].", "content": "Oxygen tension (pO2) in cerebral cortex was measured by polarographic method in unanesthetized rabbits. Intravenous administration (25 mg/kg) of carbonic anhydrase inhibitors (acetazolamide, methazolamide, dichlorphenamide, sulthiame) induced an early important rise of cortical p O2, which is not dependent on increase of p O2 and p CO2 and decrease of pH in arterial blood. High dosage of acetazolamide (250 mg/kg) produced the same effect and did not suppress the increase of cortical p O2 under air-CO2 inhalation. This result suggests that CO2 might act specifically upon cerebral vessels.", "contents": "[Increase in the oxygen available to the cerebral cortex after the administration of carbonic anhydrase inhibitors]. Oxygen tension (pO2) in cerebral cortex was measured by polarographic method in unanesthetized rabbits. Intravenous administration (25 mg/kg) of carbonic anhydrase inhibitors (acetazolamide, methazolamide, dichlorphenamide, sulthiame) induced an early important rise of cortical p O2, which is not dependent on increase of p O2 and p CO2 and decrease of pH in arterial blood. High dosage of acetazolamide (250 mg/kg) produced the same effect and did not suppress the increase of cortical p O2 under air-CO2 inhalation. This result suggests that CO2 might act specifically upon cerebral vessels."}
{"id": "PMID:15733", "title": "An extrarenal source of \"renin-like\" activity in anephric man.", "content": "To examine extrarenal sources of \"renin-like\" activity plasma was obtained from 19 anephric males. Plasma renin activity (PRA), concentration (PRC) (obtained after addition of exogenous renin substrate) and total renin concentration (TRC) (obtained after acid-activation of plasma and subsequent incubation with exogenous renin substrate) demonstrated values for several anephric patients comparable or above those seen in plasma from 10 normal subjects. Incubation of untreated plasma (PRA and PRC) and acid-dialyzed plasma (TRC) for angiotensin I generation was performed at pH 7.5, at 37 degrees C with EDTA, dimercaprol, and 8-OH-quinoline as angiotensinase and converting enzyme inhibitors. The pH optimum for acid-activation of TRC in anephric plasma was the same as that in normal plasma (pH 3.3). Molecular weight determinations following Sephadex gel chromatography demonstrated that the renin-like enzyme in normal plasma had a molecular weight of about 42,000 before and after acid-activation, while that in anephric plasma had a molecular weight of approximately 61,000. A saliva sample from one anephric subject with the highest levels of PRA, PRC, and TRC in plasma also demonstrated measurable amounts of PRA, PRC, and TRC. The molecular weight of this salivary \"renin-like\" activity also was 61,000. These observations suggest a possible extrarenal source of \"renin-like\" activity in anephric man. The physiological significance of these studies remains to be clarified.", "contents": "An extrarenal source of \"renin-like\" activity in anephric man. To examine extrarenal sources of \"renin-like\" activity plasma was obtained from 19 anephric males. Plasma renin activity (PRA), concentration (PRC) (obtained after addition of exogenous renin substrate) and total renin concentration (TRC) (obtained after acid-activation of plasma and subsequent incubation with exogenous renin substrate) demonstrated values for several anephric patients comparable or above those seen in plasma from 10 normal subjects. Incubation of untreated plasma (PRA and PRC) and acid-dialyzed plasma (TRC) for angiotensin I generation was performed at pH 7.5, at 37 degrees C with EDTA, dimercaprol, and 8-OH-quinoline as angiotensinase and converting enzyme inhibitors. The pH optimum for acid-activation of TRC in anephric plasma was the same as that in normal plasma (pH 3.3). Molecular weight determinations following Sephadex gel chromatography demonstrated that the renin-like enzyme in normal plasma had a molecular weight of about 42,000 before and after acid-activation, while that in anephric plasma had a molecular weight of approximately 61,000. A saliva sample from one anephric subject with the highest levels of PRA, PRC, and TRC in plasma also demonstrated measurable amounts of PRA, PRC, and TRC. The molecular weight of this salivary \"renin-like\" activity also was 61,000. These observations suggest a possible extrarenal source of \"renin-like\" activity in anephric man. The physiological significance of these studies remains to be clarified."}
{"id": "PMID:15736", "title": "An inactive renin in human plasma.", "content": "Normal human plasma contains an active form of renin that is activated by acidification to pH 3.0 and comprises 56% of the total renin. In our study, inactive renin was also present in plasma from five anephric persons, and the proportion of active to inactive renin in these subjects was similar to normal. Plasma from normal pregnant women contained increased concentrations of inactive renin and the proportion of inactive renin was raised to around 66%. Plasma from persons with renal hypertension contained varying amounts of inactive renin but the mean percentage (35%) was lower than normal. An infusion of saralasin sufficient to lower the blood pressure in five subjects with renal hypertension resulted in a rise in active renin concentration but no change in the concentration of inactive renin. Plasma angiotensin II correlated with active renin but not with inactive renin, suggesting that the inactive renin does not produce angiotensin II in vivo.", "contents": "An inactive renin in human plasma. Normal human plasma contains an active form of renin that is activated by acidification to pH 3.0 and comprises 56% of the total renin. In our study, inactive renin was also present in plasma from five anephric persons, and the proportion of active to inactive renin in these subjects was similar to normal. Plasma from normal pregnant women contained increased concentrations of inactive renin and the proportion of inactive renin was raised to around 66%. Plasma from persons with renal hypertension contained varying amounts of inactive renin but the mean percentage (35%) was lower than normal. An infusion of saralasin sufficient to lower the blood pressure in five subjects with renal hypertension resulted in a rise in active renin concentration but no change in the concentration of inactive renin. Plasma angiotensin II correlated with active renin but not with inactive renin, suggesting that the inactive renin does not produce angiotensin II in vivo."}
{"id": "PMID:15737", "title": "Effect of beta-blocking agents and angiotensin II on isoproterenol-stimulated renin release from rat kidney slices.", "content": "Mechanisms by which beta-blocking agents decrease blood pressure and suppress renin release are incompletely understood. We previously demonstrated that renin release by kidney slices may be increased by beta-adrenergic agonists, and the present communication contains our results on the effects of 15 beta-blocking agents and angiotensin II on isoproterenol-stimulated renin release. None of the beta-blocking compounds inhibited basal renin release. Each agent was evaluated at concentrations ranging from 10-8 to 10-5 m and three different dose-response curve patterns were observed: (1) Metoprolol, acebutolol, labetalol, and d-propranolol had no effect on isoproterenol-stimulated renin release at any concentration, whereas pindolol and bufuralol demonstrated minimal inhibition at 10-5 m only. (2) Isoproterenol stimulation was completely inhibited when dl- or l-propranolol, alprenolol, and sotalol were administered at doses ranging between 5 x 10-6 and 10-6 m; but greater concentration of these agents resulted in reappearance of the isoproterenol response. (3) Dose-related inhibition was observed with practolol, oxprenolol, timolol, nadolol, and atenolol at concentrations ranging from 10-8 to 10-5 m. Basal renin release was significantly (P is less than 0.01) inhibited by angiotensin II at 10-6 m, which also inhibited isoproterenol-stimulated renin release in a dose-related fashion. [Sar1, Ala8] angiotensin II had no direct effects on either basal or isoproterenol-stimulated renin release, but blocked the inhibitory action of angiotensin II on these parameters. There are three different effects of beta-blocking agents on isoproterenol-stimulated renin release which can only partially be explained by their presently ascribed pharmacological properties. (Beta 1- and beta2-agonists, intrinsic sympathomimetic activity, membrane-stabilizing actions). Angiotensin II inhibition of renin release appears to be functionally related to adrenergic pathways.", "contents": "Effect of beta-blocking agents and angiotensin II on isoproterenol-stimulated renin release from rat kidney slices. Mechanisms by which beta-blocking agents decrease blood pressure and suppress renin release are incompletely understood. We previously demonstrated that renin release by kidney slices may be increased by beta-adrenergic agonists, and the present communication contains our results on the effects of 15 beta-blocking agents and angiotensin II on isoproterenol-stimulated renin release. None of the beta-blocking compounds inhibited basal renin release. Each agent was evaluated at concentrations ranging from 10-8 to 10-5 m and three different dose-response curve patterns were observed: (1) Metoprolol, acebutolol, labetalol, and d-propranolol had no effect on isoproterenol-stimulated renin release at any concentration, whereas pindolol and bufuralol demonstrated minimal inhibition at 10-5 m only. (2) Isoproterenol stimulation was completely inhibited when dl- or l-propranolol, alprenolol, and sotalol were administered at doses ranging between 5 x 10-6 and 10-6 m; but greater concentration of these agents resulted in reappearance of the isoproterenol response. (3) Dose-related inhibition was observed with practolol, oxprenolol, timolol, nadolol, and atenolol at concentrations ranging from 10-8 to 10-5 m. Basal renin release was significantly (P is less than 0.01) inhibited by angiotensin II at 10-6 m, which also inhibited isoproterenol-stimulated renin release in a dose-related fashion. [Sar1, Ala8] angiotensin II had no direct effects on either basal or isoproterenol-stimulated renin release, but blocked the inhibitory action of angiotensin II on these parameters. There are three different effects of beta-blocking agents on isoproterenol-stimulated renin release which can only partially be explained by their presently ascribed pharmacological properties. (Beta 1- and beta2-agonists, intrinsic sympathomimetic activity, membrane-stabilizing actions). Angiotensin II inhibition of renin release appears to be functionally related to adrenergic pathways."}
{"id": "PMID:15738", "title": "alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium.", "content": "We determined the effect of alpha-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of alpha-adrenergic receptors with either phenylephrine (10(-8) M to 10(-6) M) or epinephrine (10(-8) M to 10(-6) M) plus propranolol (10(-6) M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10(-6) M). Phenylephrine (10(-5)M attenuated cyclic AMP generation in response to isoproterenol (10(-8) M and 10(-5) M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10(-6) M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by beta-adrenergic receptors, whereas decreases appear to by mediated by alpha-adrenergic receptors.", "contents": "alpha-Adrenergic reduction of cyclic adenosine monophosphate concentrations in rat myocardium. We determined the effect of alpha-adrenergic receptor stimulation on cyclic adenosine monophosphate (cyclic AMP) concentrations in isolated myocytes derived from adult rat hearts and in isolated perfused rat hearts. Activation of alpha-adrenergic receptors with either phenylephrine (10(-8) M to 10(-6) M) or epinephrine (10(-8) M to 10(-6) M) plus propranolol (10(-6) M) resulted in a reduction in cyclic AMP levels in isolated myocytes. The action of phenylephrine was antagonized by phentolamine (10(-6) M). Phenylephrine (10(-5)M attenuated cyclic AMP generation in response to isoproterenol (10(-8) M and 10(-5) M). However, this effect of phenylephrine was not antagonized by phentolamine. Elevation of cyclic AMP concentrations produced by glucagon and by theophylline in isolated myocytes was attenuated by phenylephrine and by epinephrine plus propranolol and the attenuation was antagonized by phentolamine. In isolated perfused rat hearts epinephrine (10(-6) M), when given with propranolol, diminished the rate of development of tension and also reduced tissue levels of cyclic AMP. Epinephrine alone, as well as isoproterenol, increased contractility and myocardial cyclic AMP concentrations as expected. These results indicate that catecholamines may increase or decrease cyclic AMP levels in rat myocardium, depending on the intensity of stimulation of receptor types. Increases are mediated by beta-adrenergic receptors, whereas decreases appear to by mediated by alpha-adrenergic receptors."}
{"id": "PMID:15739", "title": "Detection of errors in methylmalonyl-CoA metabolism by using amniotic fluid.", "content": "We report a method for rapid prenatal detection of methylmalonic acidemia, consisting of measuring methylmalonly-CoA mutase (EC 5.4.99.2) activity in non-cultured amniotic cells and measuring the concentration of methylmalonate in the amniotic fluid. Immediate stabilization of the mutase activity in the non-cultured amniotic cell by its coenzyme adenosycobalamin, and use of methylmalonyl-CoA with high specific activity gives mutase activity comparable to that of cultured amniotic cells or normal fibroblasts. Consequently, findings of low mutase activity and a hight concentration of methylmalonate in the amniotic fluid allows accurate diagnosis of the vitamin B12-nonresponsive form of methylmalonic acidemia. These results can be obtained in two days. For the vitamin B12-responsive form, the correct diagnosis depends upon finding amniotic fluid methylmalonate, because cells from these patients will display normal methylmalony-CoA mutase activity after adenosylcobalamin is added. Problems in interpreting data on bloody samples and the limitations of the method are discussed.", "contents": "Detection of errors in methylmalonyl-CoA metabolism by using amniotic fluid. We report a method for rapid prenatal detection of methylmalonic acidemia, consisting of measuring methylmalonly-CoA mutase (EC 5.4.99.2) activity in non-cultured amniotic cells and measuring the concentration of methylmalonate in the amniotic fluid. Immediate stabilization of the mutase activity in the non-cultured amniotic cell by its coenzyme adenosycobalamin, and use of methylmalonyl-CoA with high specific activity gives mutase activity comparable to that of cultured amniotic cells or normal fibroblasts. Consequently, findings of low mutase activity and a hight concentration of methylmalonate in the amniotic fluid allows accurate diagnosis of the vitamin B12-nonresponsive form of methylmalonic acidemia. These results can be obtained in two days. For the vitamin B12-responsive form, the correct diagnosis depends upon finding amniotic fluid methylmalonate, because cells from these patients will display normal methylmalony-CoA mutase activity after adenosylcobalamin is added. Problems in interpreting data on bloody samples and the limitations of the method are discussed."}
{"id": "PMID:15740", "title": "The effects of ethanol (0.75 g/kg body weight) on the activities of selected enzymes in sera of healthy young adults: 1. Intermediate-term effects.", "content": "We report the intermediate-term effects of three consecutive evenings of moderate ethanol ingestion (0.75 g/kg body weight each evening) on activity values for alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in sera of nine apparently healthy young adults. We define \"intermediate-term\" effects as those occurring between 10 h and 100 h after completion of the ethanol consumption schedule. The most pronounced changes in enzyme activity for the group of volunteers were: gamma-glutamyltransferase, +25% at 60 h after ethanol ingestion; alanine aminotransferase, +12% at 60 h after ethanol; and aspartate aminotransferase,--12% at 60 h after ethanol. All three enzymes exhibited similar time courses, i.e., mean peak activity changes were observed at 60 h, and all three mean enzyme activity values returned to near baseline by 100 h. The possible explanations for the observed changes and the clinical significance are discussed.", "contents": "The effects of ethanol (0.75 g/kg body weight) on the activities of selected enzymes in sera of healthy young adults: 1. Intermediate-term effects. We report the intermediate-term effects of three consecutive evenings of moderate ethanol ingestion (0.75 g/kg body weight each evening) on activity values for alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in sera of nine apparently healthy young adults. We define \"intermediate-term\" effects as those occurring between 10 h and 100 h after completion of the ethanol consumption schedule. The most pronounced changes in enzyme activity for the group of volunteers were: gamma-glutamyltransferase, +25% at 60 h after ethanol ingestion; alanine aminotransferase, +12% at 60 h after ethanol; and aspartate aminotransferase,--12% at 60 h after ethanol. All three enzymes exhibited similar time courses, i.e., mean peak activity changes were observed at 60 h, and all three mean enzyme activity values returned to near baseline by 100 h. The possible explanations for the observed changes and the clinical significance are discussed."}
{"id": "PMID:15741", "title": "New substrate for fluorometric determination of gamma-glutamyltransferase activity in serum.", "content": "We describe the preparation of a new substrate, N-gamma-L-glutamyl-5-aminoisophthalic acid dimethyl ester hydro-chloride, for the fluorometric determination of gamma-glutamyltransferase activity in serum by the \"front-surface\" technique. Details of the resulting method are provided. The final reaction mixture contains 4 mmol of the substrate per liter of tris(hydroxymethyl)aminomethane (100 mmol/liter) and glycylglycine (75 mmol/liter) at pH 8.2 (25 degrees C).", "contents": "New substrate for fluorometric determination of gamma-glutamyltransferase activity in serum. We describe the preparation of a new substrate, N-gamma-L-glutamyl-5-aminoisophthalic acid dimethyl ester hydro-chloride, for the fluorometric determination of gamma-glutamyltransferase activity in serum by the \"front-surface\" technique. Details of the resulting method are provided. The final reaction mixture contains 4 mmol of the substrate per liter of tris(hydroxymethyl)aminomethane (100 mmol/liter) and glycylglycine (75 mmol/liter) at pH 8.2 (25 degrees C)."}
{"id": "PMID:15742", "title": "Gamma-glutamyltransferase activity in plasma: statistical distributions, individual variations, and reference intervals.", "content": "Measurement of gamma-glutamyltransferase activity in plasma provides a useful index to liver function. Using as our study population those persons coming to the Center for Preventive Medicine, we described and measured the significance and importance of physiological and environmental variations. We established a classification for the variation factors. The three most important factors affecting this activity were drug intake, alcohol consumption, and excessive weight, followed by sex and age. We suggest a preliminary group of reference intervals for healthy subjects to be used in interpreting a laboratory test.", "contents": "Gamma-glutamyltransferase activity in plasma: statistical distributions, individual variations, and reference intervals. Measurement of gamma-glutamyltransferase activity in plasma provides a useful index to liver function. Using as our study population those persons coming to the Center for Preventive Medicine, we described and measured the significance and importance of physiological and environmental variations. We established a classification for the variation factors. The three most important factors affecting this activity were drug intake, alcohol consumption, and excessive weight, followed by sex and age. We suggest a preliminary group of reference intervals for healthy subjects to be used in interpreting a laboratory test."}
{"id": "PMID:15743", "title": "Vitamin B12 radioassay with oyster toadfish (Opsanus tau) serum as binder.", "content": "We describe a vitamin B12 radioassay in which oyster toadfish (Opsanus tau) serum is used as the binding protein. The serum is quite stable and has a high capacity and high binding affinity (K greater than 10(12) liter/mol) for vitamin B12. The binding is not significantly affected by temperature, the presence of denatured proteins, or the amount of vitamin B12 present. The radioassay is reproducible (CV 4.4%) within assay, 7.8% between assays) and sensitive (12 ng/liter). Assay accuracy is unaffected by the protein in serum or by reasonable variations in incubation temperature and time.", "contents": "Vitamin B12 radioassay with oyster toadfish (Opsanus tau) serum as binder. We describe a vitamin B12 radioassay in which oyster toadfish (Opsanus tau) serum is used as the binding protein. The serum is quite stable and has a high capacity and high binding affinity (K greater than 10(12) liter/mol) for vitamin B12. The binding is not significantly affected by temperature, the presence of denatured proteins, or the amount of vitamin B12 present. The radioassay is reproducible (CV 4.4%) within assay, 7.8% between assays) and sensitive (12 ng/liter). Assay accuracy is unaffected by the protein in serum or by reasonable variations in incubation temperature and time."}
{"id": "PMID:15744", "title": "Canaline carbamoyltransferase in human liver as part of a metabolic cycle in which guanidino compounds are formed.", "content": "This and previous papers examine the reasons for the relationship between the concentrations of guanidino-succinate and guanidinoacetate in human urine. With the demonstration here that extracts of human liver-tissue can mediate ureidohomoserine formation from canaline [(2-amino-4-aminooxy)-butyric acid] and carbamoyl phosphate, all steps in a cycle proposed for the production of guanidinoacetate and guanidinosuccinate have been documented. This includes synthesis of canavaninosuccinate from aspartate and ureidohomoserine, reductive cleavage of canavaninosuccinate to form guanidinosuccinate and homoserine, or, alternatively, lytic action on canavaninosuccinate to form fumarate and canavanine, and transamidination to glycine to form guanidinoacetate, regenerating the canaline. We propose that canaline originates from aspartate, but the precise mechanism by which canaline is formed needs to be elucidated.", "contents": "Canaline carbamoyltransferase in human liver as part of a metabolic cycle in which guanidino compounds are formed. This and previous papers examine the reasons for the relationship between the concentrations of guanidino-succinate and guanidinoacetate in human urine. With the demonstration here that extracts of human liver-tissue can mediate ureidohomoserine formation from canaline [(2-amino-4-aminooxy)-butyric acid] and carbamoyl phosphate, all steps in a cycle proposed for the production of guanidinoacetate and guanidinosuccinate have been documented. This includes synthesis of canavaninosuccinate from aspartate and ureidohomoserine, reductive cleavage of canavaninosuccinate to form guanidinosuccinate and homoserine, or, alternatively, lytic action on canavaninosuccinate to form fumarate and canavanine, and transamidination to glycine to form guanidinoacetate, regenerating the canaline. We propose that canaline originates from aspartate, but the precise mechanism by which canaline is formed needs to be elucidated."}
{"id": "PMID:15745", "title": "Diurnal variations of urinary enzyme excretion.", "content": "Variations in the urinary excretion of arylsulphatase A, beta-galactosidase, alpha-glucosidase and beta-glucuronidase throughout a 24-h period were studied in 8 healthy subjects. Urine was collected at 3-h intervals and enzyme activities were assayed after gelfiltration of the urine specimens. Significant intra-individual changes of the excretion of all 4 enzymes during the 24-h period were found. Enzyme output was high between 3 a.m. and 9 a.m. and low during the afternoon and evening hours. The most striking pattern was seen for arylsulphatase A. Diurnal variations of urinary enzyme excretion seemed not to be flow dependent. Both modes of expression of enzyme output (mU/min or U/g creatinine) gave corresponding results. It is concluded that for the measurement of the excretion of these enzymes urine should be collected during a fixed time interval, e.g. from 6 a.m. to 9 a.m.", "contents": "Diurnal variations of urinary enzyme excretion. Variations in the urinary excretion of arylsulphatase A, beta-galactosidase, alpha-glucosidase and beta-glucuronidase throughout a 24-h period were studied in 8 healthy subjects. Urine was collected at 3-h intervals and enzyme activities were assayed after gelfiltration of the urine specimens. Significant intra-individual changes of the excretion of all 4 enzymes during the 24-h period were found. Enzyme output was high between 3 a.m. and 9 a.m. and low during the afternoon and evening hours. The most striking pattern was seen for arylsulphatase A. Diurnal variations of urinary enzyme excretion seemed not to be flow dependent. Both modes of expression of enzyme output (mU/min or U/g creatinine) gave corresponding results. It is concluded that for the measurement of the excretion of these enzymes urine should be collected during a fixed time interval, e.g. from 6 a.m. to 9 a.m."}
{"id": "PMID:15747", "title": "Properties of amylase-linked immunoglobulins.", "content": "In this report, the properties of eight cases of amylase-linked immunoglobulins were gel filtration using Sephadex G-200 superfine. The class of heavy chain of amylase-linked immunoglobulins was proved to be gamma in four cases and alpha in three cases by immunoelectrophoresis followed by amylase activity staining. In one of the cases, the precipitin line against light chain lambda could be visualized only after treatment with 0.1 M 2-mercaptoethanol. Then, the type of light chain was determined to be exclusively lambda irrespective of heavy chain classes. In two cases, the immunoglobulin complexes were partially dissociated into normal amylase and immunoglobulin G at pH 8.6, and completely dissociated at pH 9.0. In three cases, the complexes were completely dissociated at pH 8.6. The precipitin line of papain treated amylase-linked immunoglobulin G against anti-Fc was not. This fact suggests that the binding site of amylase-linked immunoglobulins G was located in the Fab portion of immunoglobulin molecule and that the complexes are specific antigen-antibody complexes. Treatment with Con-A Sepharose caused the dissociation of the amylase-immunoglobulin complexes. It is suggested that the changes in the conformation of amylase-linked immunoglobulin causes the dissociation of this immuno-complex. Thus, it is elucidated that the complexes of amylase and immunoglobulins are specific antigen-antibody complexes, and that these complexes must be recognized as one of the circulating autoantibodies in plasma, and must be clearly distinguished from the other unknown macromolecular amylase complexes.", "contents": "Properties of amylase-linked immunoglobulins. In this report, the properties of eight cases of amylase-linked immunoglobulins were gel filtration using Sephadex G-200 superfine. The class of heavy chain of amylase-linked immunoglobulins was proved to be gamma in four cases and alpha in three cases by immunoelectrophoresis followed by amylase activity staining. In one of the cases, the precipitin line against light chain lambda could be visualized only after treatment with 0.1 M 2-mercaptoethanol. Then, the type of light chain was determined to be exclusively lambda irrespective of heavy chain classes. In two cases, the immunoglobulin complexes were partially dissociated into normal amylase and immunoglobulin G at pH 8.6, and completely dissociated at pH 9.0. In three cases, the complexes were completely dissociated at pH 8.6. The precipitin line of papain treated amylase-linked immunoglobulin G against anti-Fc was not. This fact suggests that the binding site of amylase-linked immunoglobulins G was located in the Fab portion of immunoglobulin molecule and that the complexes are specific antigen-antibody complexes. Treatment with Con-A Sepharose caused the dissociation of the amylase-immunoglobulin complexes. It is suggested that the changes in the conformation of amylase-linked immunoglobulin causes the dissociation of this immuno-complex. Thus, it is elucidated that the complexes of amylase and immunoglobulins are specific antigen-antibody complexes, and that these complexes must be recognized as one of the circulating autoantibodies in plasma, and must be clearly distinguished from the other unknown macromolecular amylase complexes."}
{"id": "PMID:15748", "title": "Determination of total carbon dioxide in serum and plasma using a carbonate ion-selective membrane electrode.", "content": "A new manual method for the determination of carbon dioxide content in serum and plasma, based on the potentiometric measurement of carbonate, is proposed and evaluated. The new method offers good precision and accuracy in the physiological concentration range as shown by detailed studies on synthetic samples, reference standards, and actual patient samples. Moreover, the method yields results which correlate very well with analyses carried out using various conventional techniques. It is expected that the proposed method could be used for manual determinations of CO2 content, especially where rapid start-up time, minimal sample treatment, and low cost are of importance.", "contents": "Determination of total carbon dioxide in serum and plasma using a carbonate ion-selective membrane electrode. A new manual method for the determination of carbon dioxide content in serum and plasma, based on the potentiometric measurement of carbonate, is proposed and evaluated. The new method offers good precision and accuracy in the physiological concentration range as shown by detailed studies on synthetic samples, reference standards, and actual patient samples. Moreover, the method yields results which correlate very well with analyses carried out using various conventional techniques. It is expected that the proposed method could be used for manual determinations of CO2 content, especially where rapid start-up time, minimal sample treatment, and low cost are of importance."}
{"id": "PMID:15751", "title": "Clotting in dialyzers due to low pH of dialysis fluid.", "content": "During November and December 1975 frequent clotting occurred in the extracorporeal circuits of different dialyzers used in our unit. After installation of new automatically regenerating ion exchange resin columns,, the pH of deionized water ranged from 4.2 to 8.4 during 24 hr periods. Dialysate pH ranged between 5.3 and 8.2, and the patient's whole blood pHs ranged from 7.15 to 7.4 at the dialyzer inlet and from 6.2 (!) to 7.4 at the outlet. A strong correlation was seen between the acidity of the water and the frequency of clotting, and it was considered possible that the clotting was due to structural changes within the heparin molecules induced by the low pH. Following the introduction of an automatic titration device into our dialyzate preparation system, clotting with consecutive blood loss and subjective clinical symptoms have disappeared.", "contents": "Clotting in dialyzers due to low pH of dialysis fluid. During November and December 1975 frequent clotting occurred in the extracorporeal circuits of different dialyzers used in our unit. After installation of new automatically regenerating ion exchange resin columns,, the pH of deionized water ranged from 4.2 to 8.4 during 24 hr periods. Dialysate pH ranged between 5.3 and 8.2, and the patient's whole blood pHs ranged from 7.15 to 7.4 at the dialyzer inlet and from 6.2 (!) to 7.4 at the outlet. A strong correlation was seen between the acidity of the water and the frequency of clotting, and it was considered possible that the clotting was due to structural changes within the heparin molecules induced by the low pH. Following the introduction of an automatic titration device into our dialyzate preparation system, clotting with consecutive blood loss and subjective clinical symptoms have disappeared."}
{"id": "PMID:15753", "title": "Influence of intrinsic sympathomimetic activity and cardioselectivity on beta adrenoceptor blockade.", "content": "Dose-response curves for propranolol and oxprenolol were studied in healthy volunteers, with a standardized excercise test and percentage reduction in excercise heart rate (EHR) as the index of drug effect. The dose-response curves obtained were compared with similar curves previously reported for sotalol, practolol, and atenolol with identical experimental methods. Two distinct types of response were identified: in the first, shown by propranolol and sotalol, increasing doses of the beta adrenoceptor-blocking drug continued to produce increasing effects to the limits of the dose levels examined; with the second (oxprenolol and practolol), increasing the dose initially resulted in substantial increase in effect but subsequently larger doses produced almost no increase in effect. Consideration of the additional properties of these beta adrenoceptor-blocking drugs revealed that both practolol and oxprenolol have intrinsic sympathomimetric activity (ISA), whereas propranolol and sotalol do not. In addition, practolol is cardioselective. Further investigation of the possible influence of ISA or cardioselectivity on beta adrenoceptor-blocking activity was undertaken by studying the effects of combinations of drugs on EHR. Sotalol produced greater effect when given 2 hr after sotalol, oxprenolol, practolol, or atenolol. When oxprenolol was given after sotalol or oxprenolol, or practolol was given after sotalol or practolol, there was no further increase in percentage reduction in EHR. When atenolol was given, the combinations of sotalol and atenolol together with two doses either of sotalol or atenolol all induced increases and similar final percentage reductions in EHR. Thus atenolol induces effects like those of sotalol, which are quite different from those of oxprenolol or practolol. The presence or absence of ISA would appear to be the important difference between these two groups of drugs: ISA would, therefore, appear to be demonstrated in man by flattening of the dose-response curves with exercise.", "contents": "Influence of intrinsic sympathomimetic activity and cardioselectivity on beta adrenoceptor blockade. Dose-response curves for propranolol and oxprenolol were studied in healthy volunteers, with a standardized excercise test and percentage reduction in excercise heart rate (EHR) as the index of drug effect. The dose-response curves obtained were compared with similar curves previously reported for sotalol, practolol, and atenolol with identical experimental methods. Two distinct types of response were identified: in the first, shown by propranolol and sotalol, increasing doses of the beta adrenoceptor-blocking drug continued to produce increasing effects to the limits of the dose levels examined; with the second (oxprenolol and practolol), increasing the dose initially resulted in substantial increase in effect but subsequently larger doses produced almost no increase in effect. Consideration of the additional properties of these beta adrenoceptor-blocking drugs revealed that both practolol and oxprenolol have intrinsic sympathomimetric activity (ISA), whereas propranolol and sotalol do not. In addition, practolol is cardioselective. Further investigation of the possible influence of ISA or cardioselectivity on beta adrenoceptor-blocking activity was undertaken by studying the effects of combinations of drugs on EHR. Sotalol produced greater effect when given 2 hr after sotalol, oxprenolol, practolol, or atenolol. When oxprenolol was given after sotalol or oxprenolol, or practolol was given after sotalol or practolol, there was no further increase in percentage reduction in EHR. When atenolol was given, the combinations of sotalol and atenolol together with two doses either of sotalol or atenolol all induced increases and similar final percentage reductions in EHR. Thus atenolol induces effects like those of sotalol, which are quite different from those of oxprenolol or practolol. The presence or absence of ISA would appear to be the important difference between these two groups of drugs: ISA would, therefore, appear to be demonstrated in man by flattening of the dose-response curves with exercise."}
{"id": "PMID:15754", "title": "The physiologic treatment of nasal obstruction.", "content": "Although criticisms of the submucous resection of the nasal septum and turbinectomy have been given, this is not to discredit these procedures when they are truly indicated. Certainly there are anatomic deformities causing nasal obstruction wherein a submucous resection of the septum or a submucous resection of the anterior portion of the inferior turbinate would be of benefit. The surgeon performing rhinoplastic surgery must be aware of the physiologic causes of nasal obstruction. Often a combination of structural deformity and rhinitis is blocking the airway. Intranasal, intramucosal injections of long acting corticosteroids have proven to be of great benefit in the treatment of chronic allergic, vasomotor, and hypertrophic rhinitis, and they are a useful adjunct to rhinoplastic surgery.", "contents": "The physiologic treatment of nasal obstruction. Although criticisms of the submucous resection of the nasal septum and turbinectomy have been given, this is not to discredit these procedures when they are truly indicated. Certainly there are anatomic deformities causing nasal obstruction wherein a submucous resection of the septum or a submucous resection of the anterior portion of the inferior turbinate would be of benefit. The surgeon performing rhinoplastic surgery must be aware of the physiologic causes of nasal obstruction. Often a combination of structural deformity and rhinitis is blocking the airway. Intranasal, intramucosal injections of long acting corticosteroids have proven to be of great benefit in the treatment of chronic allergic, vasomotor, and hypertrophic rhinitis, and they are a useful adjunct to rhinoplastic surgery."}
{"id": "PMID:15755", "title": "Valsalva vasoconstrictor reflex in human hypertension in after beta-adrenoreceptor blockade in conscious rabbits.", "content": "1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (SEM 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner. 2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension.", "contents": "Valsalva vasoconstrictor reflex in human hypertension in after beta-adrenoreceptor blockade in conscious rabbits. 1. A Valsalva-like manoeuvre was used to elicit graded rises in total peripheral resistance (TPR) in conscious rabbits. The rises were reflex and mediated through sympathetic constrictors. Propranolol infused at different rates reaching plasma concentrations up to 240 (SEM 33) ng/ml had no effect on this reflex but reduced mean arterial pressure. However, the response was attenuated by clonidine in a dose-dependent manner. 2. Valsalva manoeuvres were used to elicit graded sympathetically mediated rises in TPR index in twenty-nine subjects with mean arterial pressure ranging from 75 to 165 mmHg. Absolute sensitivity of the constrictor response increased with rising resting TPR index, resulting in some enhancement of constrictor responses in the hypertensive subjects. It seems likely that non-autonomic factors (e.g. vessel structure) rather than hyperactive neural constrictor effects are involved in the enhanced constrictor responses in essential hypertension."}
{"id": "PMID:15756", "title": "Peripheral and central catecholaminergic neurons in genetic and experimental hypertension in rats.", "content": "1. Activity of peripheral and central catecholaminergic neurons was studied in spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats. 2. In young SHR (4 weeks) the plasma values of bpth noradrenaline and dopamine-beta-hydroxylase activity were increased compared with those of normotensive rats of the Wistar/Kyoto strain. Total catecholamines (mostly adrenaline) were not significantly different. 3. In the adrenal glands of 2-weeks-old and 4-weeks-old SHR activities of tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl transferase were decreased, compared to Wistar/Kyoto rats. 4. The adrenaline-forming enzyme was elevated in the A1 and A2 regions of the brain stem of 4-weeks-old SHR and in the A1 region of adult DOCA-salt hypertensive rats. 5. In the adrenal glands of adult DOCA-salt hypertensive rats tyrosine hydroxylase activity was increased. 6. These results implicate peripheral noradrenaline-containing neurons and central adrenaline-containing neurons in the development of genetic and experimental hypertension in rats.", "contents": "Peripheral and central catecholaminergic neurons in genetic and experimental hypertension in rats. 1. Activity of peripheral and central catecholaminergic neurons was studied in spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats. 2. In young SHR (4 weeks) the plasma values of bpth noradrenaline and dopamine-beta-hydroxylase activity were increased compared with those of normotensive rats of the Wistar/Kyoto strain. Total catecholamines (mostly adrenaline) were not significantly different. 3. In the adrenal glands of 2-weeks-old and 4-weeks-old SHR activities of tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl transferase were decreased, compared to Wistar/Kyoto rats. 4. The adrenaline-forming enzyme was elevated in the A1 and A2 regions of the brain stem of 4-weeks-old SHR and in the A1 region of adult DOCA-salt hypertensive rats. 5. In the adrenal glands of adult DOCA-salt hypertensive rats tyrosine hydroxylase activity was increased. 6. These results implicate peripheral noradrenaline-containing neurons and central adrenaline-containing neurons in the development of genetic and experimental hypertension in rats."}
{"id": "PMID:15757", "title": "The role of alpha- and beta-presynaptic receptors in the regulation of noradrenaline release elicited by nerve stimulation.", "content": "1. The presynaptic mechanisms appear to be involved in the regulation of noradrenaline release during nerve stimulation. The first one. mediated by beta-adrenoceptors, operates at low frequencies of nerve stimulation, leading to an increase in transmitter release. The second one, mediated through alpha-adrenoceptors, is triggered when higher concentrations of the transmitter are reached in the synaptic cleft, leading to inhibition of transmitter release, probably through a restriction in the availability of calcium for the secretory process. 2. It is postulated that part of the anti-hypertensive effects of drugs like clonidine, alpha-methyldopa and beta-receptor-blocking agents may be related to their long-term effects on presynaptic adrenoceptors.", "contents": "The role of alpha- and beta-presynaptic receptors in the regulation of noradrenaline release elicited by nerve stimulation. 1. The presynaptic mechanisms appear to be involved in the regulation of noradrenaline release during nerve stimulation. The first one. mediated by beta-adrenoceptors, operates at low frequencies of nerve stimulation, leading to an increase in transmitter release. The second one, mediated through alpha-adrenoceptors, is triggered when higher concentrations of the transmitter are reached in the synaptic cleft, leading to inhibition of transmitter release, probably through a restriction in the availability of calcium for the secretory process. 2. It is postulated that part of the anti-hypertensive effects of drugs like clonidine, alpha-methyldopa and beta-receptor-blocking agents may be related to their long-term effects on presynaptic adrenoceptors."}
{"id": "PMID:15758", "title": "Pharmacokinetics of beta-receptor-blocking agents in relation to their anti-hypertensive effect.", "content": "1. Beta-Recptor-blocking drugs are rapidly and completely absorbed after oral administration. Systemic availability is nevertheless incomplete for propranolol, alprenolol and oxprenolol, owing to \"first-pass' extraction by the liver. 2. Plasma half-life is between 2 and 4 h, except for sotalol (10-12 h). Plasma elimination of propranolol is reduced with decreased liver blood flow observed in congestive heart failure or during chronic propranolol therapy itself. 3. beta-Receptor blockade is usually achieved in these concentration ranges: propranolol and alprenolol, 50-100 ng/ml; oxprenolol, 500-1000 ng/ml; pindolol, 10-30 ng/ml; sotalol, 2-6 microng/ml. Higher concentrations are often found with high doses administered to hypertensive patients.", "contents": "Pharmacokinetics of beta-receptor-blocking agents in relation to their anti-hypertensive effect. 1. Beta-Recptor-blocking drugs are rapidly and completely absorbed after oral administration. Systemic availability is nevertheless incomplete for propranolol, alprenolol and oxprenolol, owing to \"first-pass' extraction by the liver. 2. Plasma half-life is between 2 and 4 h, except for sotalol (10-12 h). Plasma elimination of propranolol is reduced with decreased liver blood flow observed in congestive heart failure or during chronic propranolol therapy itself. 3. beta-Receptor blockade is usually achieved in these concentration ranges: propranolol and alprenolol, 50-100 ng/ml; oxprenolol, 500-1000 ng/ml; pindolol, 10-30 ng/ml; sotalol, 2-6 microng/ml. Higher concentrations are often found with high doses administered to hypertensive patients."}
{"id": "PMID:15759", "title": "Haemodynamic long-term effects of beta-receptor-blocking agents in hypertension: a comparison between alprenolol, atenolol, metoprolol and timolol.", "content": "1. Oxygen consumption and central haemodynamics were recorded at rest and during exercise in fifty-one men with essential hypertension (W.H.O. stage I) and repeated after 1 year on a single drug: alprenolol (n equals 10), atenolol (13) metoprolol (12) and timolol (16). 2. Mean arterial pressure was significantly reduced in all groups at rest (11-18%) and during exercise (5-11%). Heart rate was significantly reduced in all groups (20-28%) at rest and (17-26%) during exercise. Owing to increase in supine resting and exercise stroke volume in the alprenolol and atenolol group, cardiac index decreased less than heart rate---in contrast to the timolol group where cardiac index was decreased 26-32%. The calculated post-treatment total peripheral resistance was significantly increased at rest and during exercise in the timolol group. In the other groups the total peripheral resistance was significantly increased at rest when sitting, but not at rest when supine and during exercise. 3. It is concluded that the major haemodynamic changes induced in subjects with moderate and mild essential hypertension by these different beta-receptor blockers are the same, but that minor differences exist with respect to effect upon stroke volume and total peripheral resistance.", "contents": "Haemodynamic long-term effects of beta-receptor-blocking agents in hypertension: a comparison between alprenolol, atenolol, metoprolol and timolol. 1. Oxygen consumption and central haemodynamics were recorded at rest and during exercise in fifty-one men with essential hypertension (W.H.O. stage I) and repeated after 1 year on a single drug: alprenolol (n equals 10), atenolol (13) metoprolol (12) and timolol (16). 2. Mean arterial pressure was significantly reduced in all groups at rest (11-18%) and during exercise (5-11%). Heart rate was significantly reduced in all groups (20-28%) at rest and (17-26%) during exercise. Owing to increase in supine resting and exercise stroke volume in the alprenolol and atenolol group, cardiac index decreased less than heart rate---in contrast to the timolol group where cardiac index was decreased 26-32%. The calculated post-treatment total peripheral resistance was significantly increased at rest and during exercise in the timolol group. In the other groups the total peripheral resistance was significantly increased at rest when sitting, but not at rest when supine and during exercise. 3. It is concluded that the major haemodynamic changes induced in subjects with moderate and mild essential hypertension by these different beta-receptor blockers are the same, but that minor differences exist with respect to effect upon stroke volume and total peripheral resistance."}
{"id": "PMID:15760", "title": "Comparative anti-hypertensive effectiveness of beta-adrenoreceptor antagonists with different pharmacological properties: dose-response studies during acute and chronic administration.", "content": "1. Immediate and long-term blood pressure-lowering activity of five beta-adrenoreceptor antagonists with different ancillary pharmacological properties were compared in a randomized double-blind placebo controlled factorial trial in twenty-five previously untreated patients with stable uncomplicated essential hypertension. 2. In doses which produced similar reductions in exercise tachycardia, all drugs exerted similar anti-hypertensive activity, which was greater on systolic than diastolic pressure and greatest during exercise. 3. These effects were maximum within an hour and lasted for over 8 h after a single oral dose. 4. Blood pressure-lowering activity, particularly the reduction in exercise systolic pressure, was significantly related to the logarithm of the dose of each drug. 5. Anti-hypertensive activity was maximally enhanced after 4 weeks of sustained treatment at any given dose. There was no short-term habituation to treatment and substitution with placebo resulted in a return of the blood pressure to pretreatment values within 4 weeks without subsequent overshoot. 6. The blood pressure-lowering activity of these drugs was predominantly related to their common property of competitive antagonism of cardiac beta-adrenoreceptors; their ancillary pharmacological properties, with the exception of intrinsic vasodilator activity, played little part in this response.", "contents": "Comparative anti-hypertensive effectiveness of beta-adrenoreceptor antagonists with different pharmacological properties: dose-response studies during acute and chronic administration. 1. Immediate and long-term blood pressure-lowering activity of five beta-adrenoreceptor antagonists with different ancillary pharmacological properties were compared in a randomized double-blind placebo controlled factorial trial in twenty-five previously untreated patients with stable uncomplicated essential hypertension. 2. In doses which produced similar reductions in exercise tachycardia, all drugs exerted similar anti-hypertensive activity, which was greater on systolic than diastolic pressure and greatest during exercise. 3. These effects were maximum within an hour and lasted for over 8 h after a single oral dose. 4. Blood pressure-lowering activity, particularly the reduction in exercise systolic pressure, was significantly related to the logarithm of the dose of each drug. 5. Anti-hypertensive activity was maximally enhanced after 4 weeks of sustained treatment at any given dose. There was no short-term habituation to treatment and substitution with placebo resulted in a return of the blood pressure to pretreatment values within 4 weeks without subsequent overshoot. 6. The blood pressure-lowering activity of these drugs was predominantly related to their common property of competitive antagonism of cardiac beta-adrenoreceptors; their ancillary pharmacological properties, with the exception of intrinsic vasodilator activity, played little part in this response."}
{"id": "PMID:15752", "title": "Clinical pharmacokinetics of sulphasalazine.", "content": "Sulphasalazine consists of 5-aminosalicylic acid and sulphapyridine both linked together by an azo bond. Sulphasalazine is clearly useful in long-term management of ulcerative colitis and may be useful in Crohn's disease. The absorption, metabolism and excretion of sulphasalazine is similar in volunteers and patients with ulcerative colitis or Crohn's disease. Sulphasalazine serves as a vehicle to deliver its possible active components, 5-aminosalicylic acid and sulphapyridine, to the colon in higher concentrations than could be achieved by oral administration of either one alone. Sulphasalazine reaches the colon mostly unchanged and is split by gut bacteria at the azo linkage, releasing 5-aminosalicylic acid and sulphapyridine. 5-Aminosalicylic acid may act locally and is not absorbed to any great extent. On the contrary, sulphapyridine is mostly absorpbed from the colon and may act both locally, during mucosal absorption, and systemically. A positive correlation exists between serum total sulphapyridine concentration and both therapeutic efficacy and toxicity. Sulphapyridine metabolism is largely determined by inherited acetylator phenotype, either slow or fast. Slow acetylators have higher levels of free sulphapyridine and lower levels of acetylated sulphapyridine than fast acetylators, and are likely to have more toxic symptoms on equivalent doses of sulphasalazine. Therapeutic effects of sulphasalazine in ulcerative colitis and Crohn's disease correlate with serum concentrations of total sulphapyridine (20 to 50 microng/ml), and toxicity with total sulphapyridine concentration greater than 50 microng/ml. Side-effects are mostly observed among slow acetylators. In long-term therapy of ulcerative colitis doses of 2 to 3g/day of sulphasalazine are most likely to sustain remissions and avoid toxicity. During therapy with sulphasalazine, determination of acetylator phenotype and total sulphapyridine concentration can guide effective dosage and avoid side-effects. A single serum sample for free and acetylated sulphapyridine concentrations is sufficient for this purpose.", "contents": "Clinical pharmacokinetics of sulphasalazine. Sulphasalazine consists of 5-aminosalicylic acid and sulphapyridine both linked together by an azo bond. Sulphasalazine is clearly useful in long-term management of ulcerative colitis and may be useful in Crohn's disease. The absorption, metabolism and excretion of sulphasalazine is similar in volunteers and patients with ulcerative colitis or Crohn's disease. Sulphasalazine serves as a vehicle to deliver its possible active components, 5-aminosalicylic acid and sulphapyridine, to the colon in higher concentrations than could be achieved by oral administration of either one alone. Sulphasalazine reaches the colon mostly unchanged and is split by gut bacteria at the azo linkage, releasing 5-aminosalicylic acid and sulphapyridine. 5-Aminosalicylic acid may act locally and is not absorbed to any great extent. On the contrary, sulphapyridine is mostly absorpbed from the colon and may act both locally, during mucosal absorption, and systemically. A positive correlation exists between serum total sulphapyridine concentration and both therapeutic efficacy and toxicity. Sulphapyridine metabolism is largely determined by inherited acetylator phenotype, either slow or fast. Slow acetylators have higher levels of free sulphapyridine and lower levels of acetylated sulphapyridine than fast acetylators, and are likely to have more toxic symptoms on equivalent doses of sulphasalazine. Therapeutic effects of sulphasalazine in ulcerative colitis and Crohn's disease correlate with serum concentrations of total sulphapyridine (20 to 50 microng/ml), and toxicity with total sulphapyridine concentration greater than 50 microng/ml. Side-effects are mostly observed among slow acetylators. In long-term therapy of ulcerative colitis doses of 2 to 3g/day of sulphasalazine are most likely to sustain remissions and avoid toxicity. During therapy with sulphasalazine, determination of acetylator phenotype and total sulphapyridine concentration can guide effective dosage and avoid side-effects. A single serum sample for free and acetylated sulphapyridine concentrations is sufficient for this purpose."}
{"id": "PMID:15761", "title": "Within-patient comparisons between different anti-hypertensive drugs.", "content": "1. By substituting one anti-hypertensive drug for the other in a panel of hypertensive patients equipotent doses have been determined. 2. Thus 40 mg of propranolol is equivalent to 4-5 mg of pindolol, 98 mg of practolol, 128 mg of alprenolol, 49 mg of metoprolol, 42 mg of tolamolol and 4-4 mg of timolol. 3. Bendorfluazide (10 mg) is eqivalent to 1-6 mg of bumetanide, 20 mg of chlorthalidone, 35 mg of mefruside and 3-5 mg of amiloride together with 35 mg of hydrochlorthiazide. 4. Methyldopa (250 mg) is equivalent to 6-0 mg of debrisoquine and 0-5 mg of St 600 (Boehringer), which is a clonidine-like substituted imidazoline.", "contents": "Within-patient comparisons between different anti-hypertensive drugs. 1. By substituting one anti-hypertensive drug for the other in a panel of hypertensive patients equipotent doses have been determined. 2. Thus 40 mg of propranolol is equivalent to 4-5 mg of pindolol, 98 mg of practolol, 128 mg of alprenolol, 49 mg of metoprolol, 42 mg of tolamolol and 4-4 mg of timolol. 3. Bendorfluazide (10 mg) is eqivalent to 1-6 mg of bumetanide, 20 mg of chlorthalidone, 35 mg of mefruside and 3-5 mg of amiloride together with 35 mg of hydrochlorthiazide. 4. Methyldopa (250 mg) is equivalent to 6-0 mg of debrisoquine and 0-5 mg of St 600 (Boehringer), which is a clonidine-like substituted imidazoline."}
{"id": "PMID:15762", "title": "Initial treatment of the young hypertensive: thiazide diuretic or beta-adrenoreceptor-blocking agent in a single daily dose?", "content": "1. Nine men aged 20-33 years with essential hypertension measured their own blood pressure at home, lying and standing, three times daily, under conditions of everyday living. The last 14 days' readings (eighty-four observations) from control and treatment periods of at least 4 weeks' duration were used to calculate mean pressures. 2. In eight patients, propranolol (40 mg thrice daily with meals) significantly lowered \"mean blood pressure\" (diastolic+1/3[systolic-diastolic]) but methyclothiazide (5 mg with breakfast) did not. In five subjects, prindolol (5 mg thrice daily with meals) significantly lowered \"mean blood pressure\" but methyclothiazide (5 mg with breakfast) did not. 3. In six subjects there was no significant difference between \"mean blood pressure\" when taking propranolol doses 120 mg with breakfast, 60 mg with breakfast and with the evening meal, and 40 mg with each meal. In five subjects there was no significant difference between \"mean blood pressure\" when taking metoprolol 200 mg with breakfast and 100 mg with breakfast and with the evening meal. In four subjects there was no significant difference between \"mean blood pressure\" when taking prindolol 30 mg with breakfast, 15 mg with breakfast and with the evening meal, and 10 mg with each meal. 4. In young males with essential hypertension, beta-adrenoreceptor blockers were more effective than a thiazide diuretic in lowering blood pressure, and were effective in a single daily dose.", "contents": "Initial treatment of the young hypertensive: thiazide diuretic or beta-adrenoreceptor-blocking agent in a single daily dose? 1. Nine men aged 20-33 years with essential hypertension measured their own blood pressure at home, lying and standing, three times daily, under conditions of everyday living. The last 14 days' readings (eighty-four observations) from control and treatment periods of at least 4 weeks' duration were used to calculate mean pressures. 2. In eight patients, propranolol (40 mg thrice daily with meals) significantly lowered \"mean blood pressure\" (diastolic+1/3[systolic-diastolic]) but methyclothiazide (5 mg with breakfast) did not. In five subjects, prindolol (5 mg thrice daily with meals) significantly lowered \"mean blood pressure\" but methyclothiazide (5 mg with breakfast) did not. 3. In six subjects there was no significant difference between \"mean blood pressure\" when taking propranolol doses 120 mg with breakfast, 60 mg with breakfast and with the evening meal, and 40 mg with each meal. In five subjects there was no significant difference between \"mean blood pressure\" when taking metoprolol 200 mg with breakfast and 100 mg with breakfast and with the evening meal. In four subjects there was no significant difference between \"mean blood pressure\" when taking prindolol 30 mg with breakfast, 15 mg with breakfast and with the evening meal, and 10 mg with each meal. 4. In young males with essential hypertension, beta-adrenoreceptor blockers were more effective than a thiazide diuretic in lowering blood pressure, and were effective in a single daily dose."}
{"id": "PMID:15763", "title": "Control of renin secretion in vivo and in vitro in rats: arguments in favour of a precursor form of renin and of a role of a microtubular system.", "content": "1. The morphology of the juxtaglomerular apparatus, plasma renin activity, plasma renin substrate and renal renin have been studied in rats after maximal stimulation by bilateral adrenalectomy and salt depletion, and also after blocking this stimulation by deoxycorticosterone and salt load. 2. After stimulation the juxtaglomerular apparatus showed a well-developed granular endoplasmic reticulum and a low secretory granule content. Plasma renin activity was markedly elevated and plasma renin substrate was low. After blockade numerous specific granules with crystalline structures were seen and the granular endoplasmic reticulum was less developed. Plasma renin activity was now low and plasma renin substrate elevated. 3. After prior acidification of the kidney extract a significant increase of renal renin was observed in both conditions but was greater in the second group at the time when large numbers of young granules containing crystalline material were seen. 4. Kidney slices from the adrenalectomized salt-depleted rats released more renin than control slices. Vincristine did not affect this release, but inhibited release from slices stimulated by isoprenaline.", "contents": "Control of renin secretion in vivo and in vitro in rats: arguments in favour of a precursor form of renin and of a role of a microtubular system. 1. The morphology of the juxtaglomerular apparatus, plasma renin activity, plasma renin substrate and renal renin have been studied in rats after maximal stimulation by bilateral adrenalectomy and salt depletion, and also after blocking this stimulation by deoxycorticosterone and salt load. 2. After stimulation the juxtaglomerular apparatus showed a well-developed granular endoplasmic reticulum and a low secretory granule content. Plasma renin activity was markedly elevated and plasma renin substrate was low. After blockade numerous specific granules with crystalline structures were seen and the granular endoplasmic reticulum was less developed. Plasma renin activity was now low and plasma renin substrate elevated. 3. After prior acidification of the kidney extract a significant increase of renal renin was observed in both conditions but was greater in the second group at the time when large numbers of young granules containing crystalline material were seen. 4. Kidney slices from the adrenalectomized salt-depleted rats released more renin than control slices. Vincristine did not affect this release, but inhibited release from slices stimulated by isoprenaline."}
{"id": "PMID:15766", "title": "Toxicology of ipecac: a review.", "content": "The general effectiveness and safety of Ipecac syrup, per se, has not been questioned, but rather an attempt has been made to consolidate pertinent literature dealing with the toxic manifestations of Ipecac fluid extract. Ipecac contains both emetine and cephaeline and the toxicity of Ipecac fluid extract is consistent with reports on the toxicity of both compounds. The majority of the work has involved emetine since it is in higher concentration in Ipecac fluid extract than is cephaeline. Comparison of the clinical picture presented in syrup or fluid extract of Ipecac overdose and emetine toxicity in amebiasis treatment permits us to summarize the general characteristics of Ipecac alkaloid toxicity as involving primarily gastrointestinal, cardiovascular, and neuromuscular foci.", "contents": "Toxicology of ipecac: a review. The general effectiveness and safety of Ipecac syrup, per se, has not been questioned, but rather an attempt has been made to consolidate pertinent literature dealing with the toxic manifestations of Ipecac fluid extract. Ipecac contains both emetine and cephaeline and the toxicity of Ipecac fluid extract is consistent with reports on the toxicity of both compounds. The majority of the work has involved emetine since it is in higher concentration in Ipecac fluid extract than is cephaeline. Comparison of the clinical picture presented in syrup or fluid extract of Ipecac overdose and emetine toxicity in amebiasis treatment permits us to summarize the general characteristics of Ipecac alkaloid toxicity as involving primarily gastrointestinal, cardiovascular, and neuromuscular foci."}
{"id": "PMID:15794", "title": "Insect reactions related to sports.", "content": "Only the rare practicing physician does not see at least a few patients during the warm summer months who have come off second best in an encounter with a member of Hymenoptera or one or the other of the various species of the phylum Arthropoda. Next to children and certain occupational groups such as farmers, it is probable that the outdoor sports enthusiast is the most frequent victim of insect stings and bites. Often the victim is not sure just what attacked him, and the physician may have to make an educated guess based on the appearance and grouping of the wounds and on the nature of the patient's symptoms. Usually, secondary infection is the most frequent possibility after these attacks. However, the hypersensitive patient who suffers immediate or delayed allergic reaction poses the greater, if rarer problem.", "contents": "Insect reactions related to sports. Only the rare practicing physician does not see at least a few patients during the warm summer months who have come off second best in an encounter with a member of Hymenoptera or one or the other of the various species of the phylum Arthropoda. Next to children and certain occupational groups such as farmers, it is probable that the outdoor sports enthusiast is the most frequent victim of insect stings and bites. Often the victim is not sure just what attacked him, and the physician may have to make an educated guess based on the appearance and grouping of the wounds and on the nature of the patient's symptoms. Usually, secondary infection is the most frequent possibility after these attacks. However, the hypersensitive patient who suffers immediate or delayed allergic reaction poses the greater, if rarer problem."}
{"id": "PMID:15797", "title": "A plea for comprehensive treatment for the hyperkinetic child.", "content": "Having a multimodality approach to the hyperkinetic child may make the difference between success or failure in the management of the child. Frequently, one or two modes of intervention alone will not be sufficient. Although several modes of intervention have been described, the helping professional must exercise his own creativity in order to assist specific children.", "contents": "A plea for comprehensive treatment for the hyperkinetic child. Having a multimodality approach to the hyperkinetic child may make the difference between success or failure in the management of the child. Frequently, one or two modes of intervention alone will not be sufficient. Although several modes of intervention have been described, the helping professional must exercise his own creativity in order to assist specific children."}
{"id": "PMID:15802", "title": "Metabolism and disposition of trifluoperazine in the rat. II. Kinetics after oral and intravenous administration in acutely and chronically treated animals.", "content": "Male rats received 12.3 micronmol of trifluoperazine (CF3-PER) per kg orally or into the tail vein, and the kinetics of the drug and of its metabolites, 7-hydroxytrifluoperazine and desmethyltrifluoperazine, were followed from 0.5 to 8 hr after dosage. Brain, liver, lung, kidney, and plasma were analyzed by a thin-layer chromatographic method. Following iv injection, the levels of CF3-PER were much higher in brain, lung, kidney, and plasma obtained from the aorta than following oral administration, whereas the metabolite concentrations were very similar after administration by the two routes. However, CF3-PER concentrations in liver did not depend upon the route of administration. In conjunction with this fact, the poor availability of CF3-PER in the central compartment and extrahepatic tissues following oral dosage points to a pronounced first-pass effect. When CF3-PER plasma levels were measured in the portal vein of orally treated rats, the amount of drug absorbed unchanged from the intestine could be demonstrated to be 91% of the dose. A high liver extraction (about 80%) was demonstrated in vivo by sampling hepatic venous blood. Pretreatment of rats with SKF 525-A led to an impaired CF3-PER elimination and to an increase in the liver/plasma ratio. This showed that the liver extraction was due to rapid biotransformation. Orally dosed rats exhibited significantly higher levels of CF3-PER and of its demethylation product in brain, lung, and kidney when they had been pretreated for 3 weeks with 12.3 micronmol of CF3-PER per kg daily po. One and 4 hr after iv injection of 12.3 micronmol of 3H-CF3-PER per kg, total radioactivity in brain equalled the sum of the specifically analyzed compounds, whereas in lung and kidney the tritium quantity was up to 2-fold, and in liver and plasma up to 4-fold the sum of CF3-PER and its two main metabolites.", "contents": "Metabolism and disposition of trifluoperazine in the rat. II. Kinetics after oral and intravenous administration in acutely and chronically treated animals. Male rats received 12.3 micronmol of trifluoperazine (CF3-PER) per kg orally or into the tail vein, and the kinetics of the drug and of its metabolites, 7-hydroxytrifluoperazine and desmethyltrifluoperazine, were followed from 0.5 to 8 hr after dosage. Brain, liver, lung, kidney, and plasma were analyzed by a thin-layer chromatographic method. Following iv injection, the levels of CF3-PER were much higher in brain, lung, kidney, and plasma obtained from the aorta than following oral administration, whereas the metabolite concentrations were very similar after administration by the two routes. However, CF3-PER concentrations in liver did not depend upon the route of administration. In conjunction with this fact, the poor availability of CF3-PER in the central compartment and extrahepatic tissues following oral dosage points to a pronounced first-pass effect. When CF3-PER plasma levels were measured in the portal vein of orally treated rats, the amount of drug absorbed unchanged from the intestine could be demonstrated to be 91% of the dose. A high liver extraction (about 80%) was demonstrated in vivo by sampling hepatic venous blood. Pretreatment of rats with SKF 525-A led to an impaired CF3-PER elimination and to an increase in the liver/plasma ratio. This showed that the liver extraction was due to rapid biotransformation. Orally dosed rats exhibited significantly higher levels of CF3-PER and of its demethylation product in brain, lung, and kidney when they had been pretreated for 3 weeks with 12.3 micronmol of CF3-PER per kg daily po. One and 4 hr after iv injection of 12.3 micronmol of 3H-CF3-PER per kg, total radioactivity in brain equalled the sum of the specifically analyzed compounds, whereas in lung and kidney the tritium quantity was up to 2-fold, and in liver and plasma up to 4-fold the sum of CF3-PER and its two main metabolites."}
{"id": "PMID:15803", "title": "Plasma levels of real and \"apparent\" hydralazine in man and rat.", "content": "Derivatization of hydralazine in plasma under acidic conditions yields values for the concentrations of \"apparent\" hydralazine that are dependent on the pH in the derivatization step. The results have been explained by postulating the existence of acid-hydrolyzable conjugates of unknown structure. These metabolites appear to be present in rat and human plasma after oral dosing. Procedures have been developed for the selective analysis of hydralazine or its acid-labile conjugates, and applied to measurements of plasma concentrations in rat and man.", "contents": "Plasma levels of real and \"apparent\" hydralazine in man and rat. Derivatization of hydralazine in plasma under acidic conditions yields values for the concentrations of \"apparent\" hydralazine that are dependent on the pH in the derivatization step. The results have been explained by postulating the existence of acid-hydrolyzable conjugates of unknown structure. These metabolites appear to be present in rat and human plasma after oral dosing. Procedures have been developed for the selective analysis of hydralazine or its acid-labile conjugates, and applied to measurements of plasma concentrations in rat and man."}
{"id": "PMID:15804", "title": "Comparative metabolism of fenclorac in rat, dog, monkey, and man.", "content": "Fenclorac (alpha,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent, was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, monkey, and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during both the absorption and elimination phases in all species. Small quantities of m-chloro-p-cyclohexylphenylglycolic acid metabolite were also present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 hr in the rat to 6.5 hr in the dog. The principal tissues of distribution were liver, kidney, and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey, and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant-induced polyarthritis.", "contents": "Comparative metabolism of fenclorac in rat, dog, monkey, and man. Fenclorac (alpha,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent, was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, monkey, and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during both the absorption and elimination phases in all species. Small quantities of m-chloro-p-cyclohexylphenylglycolic acid metabolite were also present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 hr in the rat to 6.5 hr in the dog. The principal tissues of distribution were liver, kidney, and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey, and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant-induced polyarthritis."}
{"id": "PMID:15805", "title": "Urinary metabolites of amitriptyline in the dog.", "content": "Dogs excreted approximately 45% of an oral dose of 14C-amitriptyline (30 mg/kg) in the urine in 24 hr. Two new urinary metabolites of the drug were identified as dihydrodiol derivatives of amitriptyline and nortriptyline, respectively. The major metabolite in dog urine was 10-hydroxyamitriptyline, excreted mainly in conjugated form. Other metabolites were characterized as 10-hydroxynortriptyline, amitriptyline N-oxide, and nortriptyline. Together, these metabolites accounted for approximately 47% of the urinary radioactivity.", "contents": "Urinary metabolites of amitriptyline in the dog. Dogs excreted approximately 45% of an oral dose of 14C-amitriptyline (30 mg/kg) in the urine in 24 hr. Two new urinary metabolites of the drug were identified as dihydrodiol derivatives of amitriptyline and nortriptyline, respectively. The major metabolite in dog urine was 10-hydroxyamitriptyline, excreted mainly in conjugated form. Other metabolites were characterized as 10-hydroxynortriptyline, amitriptyline N-oxide, and nortriptyline. Together, these metabolites accounted for approximately 47% of the urinary radioactivity."}
{"id": "PMID:15806", "title": "Identification of 3-O-methyl-alpha-methyldopamine as a urinary metabolite of 3,4-methylenedioxyamphetamine in dog and monkey.", "content": "3-O-Methyl-alpha-methyldopamine has been separated by gas-liquid chromatography (GC) as a metabolite of MDA in the urine of dog and monkey. The metabolite was identified as its mono- and di-trifluoroacetyl derivatives by comparison of their GC and GC-mass spectral properties with those of synthetic compounds. The amount of metabolite increased on hydrolyzing the urine from dosed dogs and monkeys with a preparation containing beta-glucuronidase and sulfatase.", "contents": "Identification of 3-O-methyl-alpha-methyldopamine as a urinary metabolite of 3,4-methylenedioxyamphetamine in dog and monkey. 3-O-Methyl-alpha-methyldopamine has been separated by gas-liquid chromatography (GC) as a metabolite of MDA in the urine of dog and monkey. The metabolite was identified as its mono- and di-trifluoroacetyl derivatives by comparison of their GC and GC-mass spectral properties with those of synthetic compounds. The amount of metabolite increased on hydrolyzing the urine from dosed dogs and monkeys with a preparation containing beta-glucuronidase and sulfatase."}
{"id": "PMID:15807", "title": "Metabolism of pyrazole. Structure elucidation of urinary metabolites.", "content": "Pyrazole has been widely used as an inhibitor of alcohol dehydrogenase both in vivo and in vitro. Very little attention has been paid to the metabolism of this agent and possible biological activity of any metabolites. Several isotopic variants of pyrazole, both stable and radioactive, were used in a study of its metabolic fate by gas chromatography-mass spectrometry. Seven metabolites were structurally identified and included hydroxylated and conjugated derivatives of pyrazole. Two metabolites were conjugated with a pentose, perhaps indicating that pyrazole serves as a substrate in the salvage pathway of purines and pyrimidines forming pyrazole ribosides. The use of d3-pyrazole greatly enhanced structural assignment of the metabolites by revealing the metabolism at or next to a labeled carbon atom.", "contents": "Metabolism of pyrazole. Structure elucidation of urinary metabolites. Pyrazole has been widely used as an inhibitor of alcohol dehydrogenase both in vivo and in vitro. Very little attention has been paid to the metabolism of this agent and possible biological activity of any metabolites. Several isotopic variants of pyrazole, both stable and radioactive, were used in a study of its metabolic fate by gas chromatography-mass spectrometry. Seven metabolites were structurally identified and included hydroxylated and conjugated derivatives of pyrazole. Two metabolites were conjugated with a pentose, perhaps indicating that pyrazole serves as a substrate in the salvage pathway of purines and pyrimidines forming pyrazole ribosides. The use of d3-pyrazole greatly enhanced structural assignment of the metabolites by revealing the metabolism at or next to a labeled carbon atom."}
{"id": "PMID:15809", "title": "Enhanced naloxone distribution to the brain by morphine pretreatment in mice.", "content": "An increase in the disposition of naloxone to the mouse brain was observed for animals previously exposed to morphine. Compared to controls, mice receiving morphine sulfate (10 mg/kg, sc) 3 hr prior to naloxone had a 28% increase in naloxone concentration in brain (200 to 260 pmol of naloxone per g of brain) 10 min after 3H-naloxone-HCl (0.4 mg/kg, 11.0 micronCi/kg, sc) administration. Also, if similar morphine-pretreated mice received a second dose of morphine sulfate (1.0 mg/kg, sc) concurrent with 3H-naloxone-HCl, the morphine-induced enhancement of 3H-naloxone concentration in brain was unaltered. This drug-treatment protocol paralleled that used by others in pA2-analgesia assays to demonstrate sensitization to naloxone for morphine-pretreated animals. In prior (3 hr) morphine-treated animals, administration of 3H-naloxone-HCl (0.1 mg/kg, 33.3 micronCi/kg) iv resulted in an 11.0% increase in 3H-naloxone brain concentration after 1 min. Thus, the enhancement of naloxone brain concentration was independent of the route of naloxone administration. No enhancement of 3H-naloxone brain concentration could be seen 24 hr after morphine sulfate pretreatment (10 mg/kg, sc), a decline in the effect similar to that seen for morphine-induced sensitization to naloxone. Finally, when morphine pellet-implanted mice (75 mg of morphine base, 72 hr) were administered 3H-naloxone-HCl (0.4 mg/kg, 10.0 micronCi/kg, sc), only a 22.5% enhancement of 3H-naloxone concentration in brain was obtained, as opposed to a reported 8-fold increase in the potency of naloxone. Thus, although a number of similarities exist between the enhancement by morphine of naloxone concentration in brain and its sensitization to the antagonistic activity of naloxone, a quantitative correlation appears to be lacking between the two phenomena.", "contents": "Enhanced naloxone distribution to the brain by morphine pretreatment in mice. An increase in the disposition of naloxone to the mouse brain was observed for animals previously exposed to morphine. Compared to controls, mice receiving morphine sulfate (10 mg/kg, sc) 3 hr prior to naloxone had a 28% increase in naloxone concentration in brain (200 to 260 pmol of naloxone per g of brain) 10 min after 3H-naloxone-HCl (0.4 mg/kg, 11.0 micronCi/kg, sc) administration. Also, if similar morphine-pretreated mice received a second dose of morphine sulfate (1.0 mg/kg, sc) concurrent with 3H-naloxone-HCl, the morphine-induced enhancement of 3H-naloxone concentration in brain was unaltered. This drug-treatment protocol paralleled that used by others in pA2-analgesia assays to demonstrate sensitization to naloxone for morphine-pretreated animals. In prior (3 hr) morphine-treated animals, administration of 3H-naloxone-HCl (0.1 mg/kg, 33.3 micronCi/kg) iv resulted in an 11.0% increase in 3H-naloxone brain concentration after 1 min. Thus, the enhancement of naloxone brain concentration was independent of the route of naloxone administration. No enhancement of 3H-naloxone brain concentration could be seen 24 hr after morphine sulfate pretreatment (10 mg/kg, sc), a decline in the effect similar to that seen for morphine-induced sensitization to naloxone. Finally, when morphine pellet-implanted mice (75 mg of morphine base, 72 hr) were administered 3H-naloxone-HCl (0.4 mg/kg, 10.0 micronCi/kg, sc), only a 22.5% enhancement of 3H-naloxone concentration in brain was obtained, as opposed to a reported 8-fold increase in the potency of naloxone. Thus, although a number of similarities exist between the enhancement by morphine of naloxone concentration in brain and its sensitization to the antagonistic activity of naloxone, a quantitative correlation appears to be lacking between the two phenomena."}
{"id": "PMID:15808", "title": "The metabolism and toxicity of halogenated carbanilides. Biliary metabolites of 3,4,4'-trichlorocarbanilide and 3-trifluoromethyl-4,4'-dichlorocarbanilide in the rat.", "content": "In separate experiments, after repeated oral administration of 3,4,4'-trichlorocarbanilide (TCC) and 3-trifluoromethyl-4,4'-dichlorocarbanilide (TFC) to rats, the biliary metabolites of each were isolated and identified. The major TCC biliary metabolite was found to be 2'-hydroxy-TCC. This compound was isolated mainly from the nonconjugated and the glucuronide fractions. Other metabolites present in substantial quantities were 6-hydroxy-TCC and 2',6-dihydroxy-TCC mainly as glucuronides and 3'-hydroxy TCC mainly as the sulfate conjugate. Small amounts of 3',6-dihydroxy-TCC were isolated from each of the fractions. No unchanged TCC was found in the bile. Only traces of other metabolites were found, and no N-hydroxylated products were observed. The major TFC biliary metabolite was the glucuronide conjugate of 2'-hydroxy-TFC. The only other metabolite of TFC was 3'-hydroxy-TFC, which was the predominant metabolite in the sulfate-conjugated fraction.", "contents": "The metabolism and toxicity of halogenated carbanilides. Biliary metabolites of 3,4,4'-trichlorocarbanilide and 3-trifluoromethyl-4,4'-dichlorocarbanilide in the rat. In separate experiments, after repeated oral administration of 3,4,4'-trichlorocarbanilide (TCC) and 3-trifluoromethyl-4,4'-dichlorocarbanilide (TFC) to rats, the biliary metabolites of each were isolated and identified. The major TCC biliary metabolite was found to be 2'-hydroxy-TCC. This compound was isolated mainly from the nonconjugated and the glucuronide fractions. Other metabolites present in substantial quantities were 6-hydroxy-TCC and 2',6-dihydroxy-TCC mainly as glucuronides and 3'-hydroxy TCC mainly as the sulfate conjugate. Small amounts of 3',6-dihydroxy-TCC were isolated from each of the fractions. No unchanged TCC was found in the bile. Only traces of other metabolites were found, and no N-hydroxylated products were observed. The major TFC biliary metabolite was the glucuronide conjugate of 2'-hydroxy-TFC. The only other metabolite of TFC was 3'-hydroxy-TFC, which was the predominant metabolite in the sulfate-conjugated fraction."}
{"id": "PMID:15812", "title": "O-Demethylation of p-nitroanisole by Escherichia coli. Stimulation by phenobarbital.", "content": "Intact cells of the bacterium Escherichia coli ATCC 11229, can convert p-nitroanisole into p-nitrophenol. The presence of phenobarbital in the culture medium during growth of the cells results in an inhibition of bacterial cell mass and an increased ability of the bacterial cell to carry out the O-demethylation reaction. There was a linear relationship between the amount of product formed and the bacterial cell mass in the incubation mixture. Varying the substrate concentration gave a concomitant change in activity, defined as the amount of product formed per mg of bacterial cell mass per 150 min. The optimum temperature for the production of p-nitrophenol by the stimulated cells was 33 degrees C; 7.0 was the pH optimum.", "contents": "O-Demethylation of p-nitroanisole by Escherichia coli. Stimulation by phenobarbital. Intact cells of the bacterium Escherichia coli ATCC 11229, can convert p-nitroanisole into p-nitrophenol. The presence of phenobarbital in the culture medium during growth of the cells results in an inhibition of bacterial cell mass and an increased ability of the bacterial cell to carry out the O-demethylation reaction. There was a linear relationship between the amount of product formed and the bacterial cell mass in the incubation mixture. Varying the substrate concentration gave a concomitant change in activity, defined as the amount of product formed per mg of bacterial cell mass per 150 min. The optimum temperature for the production of p-nitrophenol by the stimulated cells was 33 degrees C; 7.0 was the pH optimum."}
{"id": "PMID:15810", "title": "Lung pH and pulmonary absorption of nonvolatile drugs in the rat.", "content": "The effect of pH on pulmonary absorption of nonvolatile drugs was investigated in the rat. Krebs-Ringer phosphate solutions (pH 6.2 and 7.4), Krebs-Ringer pyrophosphate solution (pH 8.4), or an unbuffered salt solution containing a drug were administered through tight-fitting tracheal cannulas to anesthetized animals. After 3 min, the lungs were removed and assayed for the amount of drug that remained. Weak acids and a weak base were absorbed most rapidly at pH values at which the drugs were least ionized. For example, with the base procainamide, 36% of the dose was absorbed at pH 6.2 and 76% at pH 8.4. With the acid sulfisoxazole, 71% was absorbed at pH 6.2 and 55% at pH 8.4. Similarly, with p-aminosalicylic acid, 77% was absorbed at pH 6.2 and 40% at pH 8.4. In contrast to these results, compounds such as urea and amitrole, which remain completely nonionized over the pH range studied, showed no change in absorption rate when the pH was varied. The two weak acids and the weak base were absorbed from an unbuffered solution as though the pH at the site of drug absorption was between 6.2 and 7.4. The absorption rate for each weak electrolyte from unbuffered solution, when compared graphically with the respective absorption rates from buffered solutions, indicated that the pH at the site of drug absorption is about 6.6.", "contents": "Lung pH and pulmonary absorption of nonvolatile drugs in the rat. The effect of pH on pulmonary absorption of nonvolatile drugs was investigated in the rat. Krebs-Ringer phosphate solutions (pH 6.2 and 7.4), Krebs-Ringer pyrophosphate solution (pH 8.4), or an unbuffered salt solution containing a drug were administered through tight-fitting tracheal cannulas to anesthetized animals. After 3 min, the lungs were removed and assayed for the amount of drug that remained. Weak acids and a weak base were absorbed most rapidly at pH values at which the drugs were least ionized. For example, with the base procainamide, 36% of the dose was absorbed at pH 6.2 and 76% at pH 8.4. With the acid sulfisoxazole, 71% was absorbed at pH 6.2 and 55% at pH 8.4. Similarly, with p-aminosalicylic acid, 77% was absorbed at pH 6.2 and 40% at pH 8.4. In contrast to these results, compounds such as urea and amitrole, which remain completely nonionized over the pH range studied, showed no change in absorption rate when the pH was varied. The two weak acids and the weak base were absorbed from an unbuffered solution as though the pH at the site of drug absorption was between 6.2 and 7.4. The absorption rate for each weak electrolyte from unbuffered solution, when compared graphically with the respective absorption rates from buffered solutions, indicated that the pH at the site of drug absorption is about 6.6."}
{"id": "PMID:15813", "title": "Comparison of the metabolism of parathion by a rat liver reconstituted mixed-function oxidase enzyme system and by a system containing cumene hydroperoxide and purified rat liver cytochrome P-450.", "content": "The metabolism of parathion by a reconstituted mixed-function oxidase enzyme system (rat liver cytochrome P-450, NADPH-cytochrome c reductase, dilauroyl phosphatidylcholine, deoxycholate, and NADPH) or a cumene hydroperoxide system (cytochrome P-450, dilauroyl phosphatidylcholine, and cumene hydroperoxide) have been compared. The products formed on incubation of parathion with both systems were paraoxon, diethyl phosphorothioic acid, diethyl phosphoric acid, p-nitrophenol, and atomic sulfur. The apparent KM values for parathion for formation of paraoxon and diethyl phosphorothioic acid with the cumene hydroperoxide system were 55 and 39 X 10(-6) M, respectively. These KM values are not significantly different. When the reconstituted system was used, apparent KM values of 2.8 x 10(-6) M for formation of paraoxon and 3.9 x 10(-6) M for The formation of diethyl phosphorothioic acid and diethyl phosphoric acid were determined. These KM values are also not significantly different. covalent binding of the sulfur atom, released in the metabolism of parathion to paraoxon, to the proteins of the reconstituted system and to cytochrome P-450 of the cumene hydroperoxide system was also examined. With both the reconstituted system and the cumene hydroperoxide system approximately 65% of the sulfur released became bound to the proteins of these enzyme systems. The binding of the sulfur atome resulted in a progressive inhibition of the metabolism of parathion by these two systems.", "contents": "Comparison of the metabolism of parathion by a rat liver reconstituted mixed-function oxidase enzyme system and by a system containing cumene hydroperoxide and purified rat liver cytochrome P-450. The metabolism of parathion by a reconstituted mixed-function oxidase enzyme system (rat liver cytochrome P-450, NADPH-cytochrome c reductase, dilauroyl phosphatidylcholine, deoxycholate, and NADPH) or a cumene hydroperoxide system (cytochrome P-450, dilauroyl phosphatidylcholine, and cumene hydroperoxide) have been compared. The products formed on incubation of parathion with both systems were paraoxon, diethyl phosphorothioic acid, diethyl phosphoric acid, p-nitrophenol, and atomic sulfur. The apparent KM values for parathion for formation of paraoxon and diethyl phosphorothioic acid with the cumene hydroperoxide system were 55 and 39 X 10(-6) M, respectively. These KM values are not significantly different. When the reconstituted system was used, apparent KM values of 2.8 x 10(-6) M for formation of paraoxon and 3.9 x 10(-6) M for The formation of diethyl phosphorothioic acid and diethyl phosphoric acid were determined. These KM values are also not significantly different. covalent binding of the sulfur atom, released in the metabolism of parathion to paraoxon, to the proteins of the reconstituted system and to cytochrome P-450 of the cumene hydroperoxide system was also examined. With both the reconstituted system and the cumene hydroperoxide system approximately 65% of the sulfur released became bound to the proteins of these enzyme systems. The binding of the sulfur atome resulted in a progressive inhibition of the metabolism of parathion by these two systems."}
{"id": "PMID:15814", "title": "Metabolism of haloforms to carbon monoxide. I. In vitro studies.", "content": "Trihalomethanes (haloforms) were metabolized to carbon monoxide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen for maximal activity. GSH alone did not serve as a cofactor; however, GSH in the presence of NADPH and oxygen produced an 8-fold increase in the metabolism of bromoform to CO. Similar results were obtained with other sulfhydryl compounds. The biotransformation of bromoform to CO was characterized with respect to time course, microsomal protein concentration, pH and temperature. The metabolism of haloforms to CO followed the halide order; thus, iodoform yielded the greatest amount of CO, whereas chloroform yielded the smallest amount. A KM of 6.78 +/- 2.71 mM was established for bromoform and the Vmax was 1.09 +/- 0.19 nmol of CO per mg of microsomal protein per min. The energy of activation for this reaction was 6.5 +/- 0.18 kcal/mol. Cytochrome P-450 was found to bind bromoform to produce a type I binding spectrum. Treatment of rats with phenobarbital or 3-methylcholanthrene increased the rate of conversion of bromoform to CO. Cobaltous chloride treatment of rats or storage of microsomal preparations at 4 degrees C reduced the rate of formation of CO from bromoform. SKF 525-A inhibited the conversion of bromoform to CO. These results suggest that haloforms are metabolized to CO via a cytochrome P-450-dependent mixed-function oxidase system.", "contents": "Metabolism of haloforms to carbon monoxide. I. In vitro studies. Trihalomethanes (haloforms) were metabolized to carbon monoxide by a rat liver microsomal fraction requiring both NADPH and molecular oxygen for maximal activity. GSH alone did not serve as a cofactor; however, GSH in the presence of NADPH and oxygen produced an 8-fold increase in the metabolism of bromoform to CO. Similar results were obtained with other sulfhydryl compounds. The biotransformation of bromoform to CO was characterized with respect to time course, microsomal protein concentration, pH and temperature. The metabolism of haloforms to CO followed the halide order; thus, iodoform yielded the greatest amount of CO, whereas chloroform yielded the smallest amount. A KM of 6.78 +/- 2.71 mM was established for bromoform and the Vmax was 1.09 +/- 0.19 nmol of CO per mg of microsomal protein per min. The energy of activation for this reaction was 6.5 +/- 0.18 kcal/mol. Cytochrome P-450 was found to bind bromoform to produce a type I binding spectrum. Treatment of rats with phenobarbital or 3-methylcholanthrene increased the rate of conversion of bromoform to CO. Cobaltous chloride treatment of rats or storage of microsomal preparations at 4 degrees C reduced the rate of formation of CO from bromoform. SKF 525-A inhibited the conversion of bromoform to CO. These results suggest that haloforms are metabolized to CO via a cytochrome P-450-dependent mixed-function oxidase system."}
{"id": "PMID:15818", "title": "Neuropsychological deficit in polydrug users. A preliminary report of the findings of the collaborative neuropsychological study of polydrug users.", "content": "The Collaborative Neuropsychological Study of Polydrug Users performed extensive neuropsychological assessments on 15 polydrug users 3 weeks after their enrollment in each of eight polydrug demonstration programs. Fifty-six (37%) of these subjects exhibited neuropsychological deficit. This deficit was partially related to increasing age, poor education and premorbid medical risk factors. The deficit was also associated with extensive and intensive use of two classes of drugs: sedatives (sleeping pills and minor tranquilizers) and opiates (heroin and other narcotic drugs). Seventeen (26%) of a comparison group of 66 psychiatric in-patients and day patients also demonstrated age- and education-correlated neuropsychological deficit. For these patients impairment was also related to lifetime experience with antipsychotic drugs and (perhaps) with clinical diagnosis of schizophrenia. Although both polydrug users and psychiatric patients revealed serious psychopathology as measured by the MMPI, the pattern of the neuropsychological test findings suggested that psychopathology alone did not account for impairment. The 3 month follow-up which is in progress should delineate further the time course and enduring features of neuropsychological deficit among polydrug users, and may establish more clearly the relationship of sedative and opiate use to such impairment. Changes in psychopathological status of both polydrug users and psychiatric patients should also help to clarify the influence of this variable on neuropsychological findings.", "contents": "Neuropsychological deficit in polydrug users. A preliminary report of the findings of the collaborative neuropsychological study of polydrug users. The Collaborative Neuropsychological Study of Polydrug Users performed extensive neuropsychological assessments on 15 polydrug users 3 weeks after their enrollment in each of eight polydrug demonstration programs. Fifty-six (37%) of these subjects exhibited neuropsychological deficit. This deficit was partially related to increasing age, poor education and premorbid medical risk factors. The deficit was also associated with extensive and intensive use of two classes of drugs: sedatives (sleeping pills and minor tranquilizers) and opiates (heroin and other narcotic drugs). Seventeen (26%) of a comparison group of 66 psychiatric in-patients and day patients also demonstrated age- and education-correlated neuropsychological deficit. For these patients impairment was also related to lifetime experience with antipsychotic drugs and (perhaps) with clinical diagnosis of schizophrenia. Although both polydrug users and psychiatric patients revealed serious psychopathology as measured by the MMPI, the pattern of the neuropsychological test findings suggested that psychopathology alone did not account for impairment. The 3 month follow-up which is in progress should delineate further the time course and enduring features of neuropsychological deficit among polydrug users, and may establish more clearly the relationship of sedative and opiate use to such impairment. Changes in psychopathological status of both polydrug users and psychiatric patients should also help to clarify the influence of this variable on neuropsychological findings."}
{"id": "PMID:15811", "title": "Disposition of carbamazepine and its 10,11-epoxide metabolite in the isolated perfused rat liver.", "content": "The disposition of carbamazepine and its metabolite, the 10,11-epoxide, was investigated in isolated perfused livers from control and phenobarbital-pretreated rats. The mean hepatic clearance of carbamazepine was 0.28 ml per min per g of liver corresponding to a mean extraction ratio of 0.16 and a mean intrinsic clearance of 0.33 ml per min g of liver. In phenobarbital-pretreated rats, there was an approximately 40% increase in the hepatic clearance due to a concomitant increase in the mean extraction ratio from 0.16 to 0.26. The carbamazepine-10,11-epoxide generated in the liver approached and attained its peak concentration more rapidly in pretreated than in control rat livers. In the latter group there was virtually no disappearance of the epoxide from the perfusate, whereas in the pretreated rat livers the perfusate concentrations declined after 90 min. The extremely low clearance of the epoxide generated by metabolism in control rat liver was confirmed by administration of the epoxide per se to the perfusion system. The mean extraction ratio of the epoxide in this situation was only 0.016 and it was unaffected by prior treatment of the rats with phenobarbital. However, the epoxids exhibited dose-dependent kinetics with a 3-fold increase in the extraction ratio when the administered dose was reduced from 500 to 166 microng. The observed induction of the hepatic clearance of carbamazepine is supportive of the involvement of this mechanism in the interaction of this drug with various other anticonvulsants in both children and adults.", "contents": "Disposition of carbamazepine and its 10,11-epoxide metabolite in the isolated perfused rat liver. The disposition of carbamazepine and its metabolite, the 10,11-epoxide, was investigated in isolated perfused livers from control and phenobarbital-pretreated rats. The mean hepatic clearance of carbamazepine was 0.28 ml per min per g of liver corresponding to a mean extraction ratio of 0.16 and a mean intrinsic clearance of 0.33 ml per min g of liver. In phenobarbital-pretreated rats, there was an approximately 40% increase in the hepatic clearance due to a concomitant increase in the mean extraction ratio from 0.16 to 0.26. The carbamazepine-10,11-epoxide generated in the liver approached and attained its peak concentration more rapidly in pretreated than in control rat livers. In the latter group there was virtually no disappearance of the epoxide from the perfusate, whereas in the pretreated rat livers the perfusate concentrations declined after 90 min. The extremely low clearance of the epoxide generated by metabolism in control rat liver was confirmed by administration of the epoxide per se to the perfusion system. The mean extraction ratio of the epoxide in this situation was only 0.016 and it was unaffected by prior treatment of the rats with phenobarbital. However, the epoxids exhibited dose-dependent kinetics with a 3-fold increase in the extraction ratio when the administered dose was reduced from 500 to 166 microng. The observed induction of the hepatic clearance of carbamazepine is supportive of the involvement of this mechanism in the interaction of this drug with various other anticonvulsants in both children and adults."}
{"id": "PMID:15816", "title": "Induction of hepatic aryl hydrocarbon hydroxylase and epoxide hydrase in Wistar rats pretreated with oral methadone hydrochloride.", "content": "Methadone-HCl added to the drinking water of adult female Wistar rats for 4 weeks produced an increase in the aryl hydrocarbon hydroxylase activity of the hepatic microsomal fraction to 222% of control levels. No change was seen in epoxide hydrase activity. In contrast, when male rats were treated similarly, there was an increase in epoxide hydrase activity to 212% of controls with no change in aryl hydrocarbon hydroxylase activity. No such changes were observed when the subcutaneous route of administration or chronic, low-dose, intraperitoneal injections were used. There were no differences in hepatic cytochrome P-450 or protein concentrations in treated animals as compared to their respective control groups. Control studies were carried out with quinine sulfate in the drinking water to decrease water intake to the level of the methadone-treated group. No elevation in either enzyme activity occurred in this control group. Similarly, paired-feeding studies showed the elevation of enzyme activity to be due to the methadone, not food deprivation. The effects of concurrent therapy of methadone with phenobarbital sodium or 3-methylcholanthrene were compared.", "contents": "Induction of hepatic aryl hydrocarbon hydroxylase and epoxide hydrase in Wistar rats pretreated with oral methadone hydrochloride. Methadone-HCl added to the drinking water of adult female Wistar rats for 4 weeks produced an increase in the aryl hydrocarbon hydroxylase activity of the hepatic microsomal fraction to 222% of control levels. No change was seen in epoxide hydrase activity. In contrast, when male rats were treated similarly, there was an increase in epoxide hydrase activity to 212% of controls with no change in aryl hydrocarbon hydroxylase activity. No such changes were observed when the subcutaneous route of administration or chronic, low-dose, intraperitoneal injections were used. There were no differences in hepatic cytochrome P-450 or protein concentrations in treated animals as compared to their respective control groups. Control studies were carried out with quinine sulfate in the drinking water to decrease water intake to the level of the methadone-treated group. No elevation in either enzyme activity occurred in this control group. Similarly, paired-feeding studies showed the elevation of enzyme activity to be due to the methadone, not food deprivation. The effects of concurrent therapy of methadone with phenobarbital sodium or 3-methylcholanthrene were compared."}
{"id": "PMID:15817", "title": "Metabolism and disposition of trifluoperazine in the rat. I. A thin-layer chromatographic method for the measurement of trifluoperazine and its metabolites in rat tissues.", "content": "A method has been developed for quantitative measurement of trifluoperazine and its metabolites, 7-hydroxytrifluoperazine and desmethyltrifluoperazine, in rat organs. Trifluoperazine sulfoxide could also be assayed, but it proved to represent a very minor part only of total biotransformation products in tissues. Alkalinized tissue homogenates were extracted with di-isopropyl ether. Following removal of the bulk of lipids, the compounds to be quantitated were separated by thin-layer chromatography and measured by ultraviolet reflectance photometry on the plates. In recovery experiments, the method proved to possess a high reproducibility. The sensitivity limit for quantitative determination was about 0.1 nmol per extract, and the limit of detectability was 0.025-0.05 nmol. The applicability of the method was shown by analyzing the tissues of rats that had received 12.3 micronmol of trifluoperazine, ip, per kg.", "contents": "Metabolism and disposition of trifluoperazine in the rat. I. A thin-layer chromatographic method for the measurement of trifluoperazine and its metabolites in rat tissues. A method has been developed for quantitative measurement of trifluoperazine and its metabolites, 7-hydroxytrifluoperazine and desmethyltrifluoperazine, in rat organs. Trifluoperazine sulfoxide could also be assayed, but it proved to represent a very minor part only of total biotransformation products in tissues. Alkalinized tissue homogenates were extracted with di-isopropyl ether. Following removal of the bulk of lipids, the compounds to be quantitated were separated by thin-layer chromatography and measured by ultraviolet reflectance photometry on the plates. In recovery experiments, the method proved to possess a high reproducibility. The sensitivity limit for quantitative determination was about 0.1 nmol per extract, and the limit of detectability was 0.025-0.05 nmol. The applicability of the method was shown by analyzing the tissues of rats that had received 12.3 micronmol of trifluoperazine, ip, per kg."}
{"id": "PMID:15815", "title": "Probenecid metabolism in vitro with rat, mouse, and human liver preparations. Studies of factors affecting the site of oxidation.", "content": "The metabolism of probenecid in vitro was investigated with rat, mouse, and human liver preparations. As in previous in vivo studies, metabolism in vitro was found to be limited to the side chain. This metabolism involved mono-N-depropylation and hydroxylation in the 2- and 3-positions (3-hydroxy probenecid was in part converted to the carboxy metabolite). Acyl glucuronide conjugation was minimal. The presence of multiple forms of microsomal oxidative enzymes was suggested by the effects of: a) phenobarbital pretreatment, b) drug-metabolizing enzyme inhibitors, and c) variations in ionic strength and buffer composition on the metabolism of probenecid.", "contents": "Probenecid metabolism in vitro with rat, mouse, and human liver preparations. Studies of factors affecting the site of oxidation. The metabolism of probenecid in vitro was investigated with rat, mouse, and human liver preparations. As in previous in vivo studies, metabolism in vitro was found to be limited to the side chain. This metabolism involved mono-N-depropylation and hydroxylation in the 2- and 3-positions (3-hydroxy probenecid was in part converted to the carboxy metabolite). Acyl glucuronide conjugation was minimal. The presence of multiple forms of microsomal oxidative enzymes was suggested by the effects of: a) phenobarbital pretreatment, b) drug-metabolizing enzyme inhibitors, and c) variations in ionic strength and buffer composition on the metabolism of probenecid."}
{"id": "PMID:15821", "title": "Inhibitory effect of immobilization stress on depression of liver tyrosine aminotransferase and tryptophan pyrrolase by glucose feeding in rats.", "content": "In alloxan diabetic rats a stimulatory effect of stress on the activity of liver phosphoenolpyruvate carboxykinase seems to be very likely. In intact animals the inhibitory effect of glucose feeding (15% glucose instead of laboratory diet and water) on the activity of liver tyrosine aminotransferase (TAT) and tryptophan pyrrolase was reconfirmed. Moreover, a reversal of this effect by immobilization for 2.5 h was observed. After a mean intake of 5.3 g glucose/100 g body weight during 16 h this reversal was only partial and after 3.4 glucose/100 g during the same time the glucose effect was abolished. Stimulation of both enzymes by corticosterone and of TAT by stress-induced release of glucagon may play a role in this reversal.", "contents": "Inhibitory effect of immobilization stress on depression of liver tyrosine aminotransferase and tryptophan pyrrolase by glucose feeding in rats. In alloxan diabetic rats a stimulatory effect of stress on the activity of liver phosphoenolpyruvate carboxykinase seems to be very likely. In intact animals the inhibitory effect of glucose feeding (15% glucose instead of laboratory diet and water) on the activity of liver tyrosine aminotransferase (TAT) and tryptophan pyrrolase was reconfirmed. Moreover, a reversal of this effect by immobilization for 2.5 h was observed. After a mean intake of 5.3 g glucose/100 g body weight during 16 h this reversal was only partial and after 3.4 glucose/100 g during the same time the glucose effect was abolished. Stimulation of both enzymes by corticosterone and of TAT by stress-induced release of glucagon may play a role in this reversal."}
{"id": "PMID:15822", "title": "Purification of bovine thyroid peroxidase.", "content": "Trypsin-solubilized peroxidase activity from beef subcellular particles was resolved by DEAE-cellulose chromatography into 5 fractions, which contained enzymatically active components that ranged in molecular size from 73,000 to 340,000 daltons. The most active fraction (mol wt, 92,000 by gel filtration) was further purified (59,000-fold overall) by chromatography on hydroxylapatite. This highly purified peroxidase preparation had an absorbance purity ratio (A410:A280) of 0.55 and oxidized iodide (I3-formation) and guaiacol at rates of 300 and 460 micronmol/min/mg, respectively, which were about 3 and 1 1/2 times, respectively, greater than any previously described preparations. The enzyme was contaminated with an inactive protein of equal size. The highly purified peroxidase preparation lost its activity within a few days even when stored at -15 C with iodide. Two of the other DEAE-cellulose fractions contained peroxidase components with estimated sizes (gel filtration) of 73,000, 96,000, and 98,000, which were further purified purified (1,600 and 15,600 fold) on hydroxylapatite. They were 1/4 to 1/40 as active as the highly purified preparation and also became increasingly labile on purification. The remaining two DEAE-cellulose fractions were heterogeneous mixtures of stable peroxidase components whose average molecular sizes (gel filtration) were 220,000, 300,000, and 340,000 daltons, and which were not amenable to further purification on hydroxylapatite. The ratio of guaiacol to iodide activity decreased from 3.0 in the particles to about 1.5 in the highly purified preparations. The turnover numbers of the purest peroxidase component (mol wt. 92,000) for iodide and guaiacol were very similar to those of highly purifed, commericial lacto- and horseradish peroxidases. The pH maxima for iodide oxidation were 7.4, 6.0, and 4.5 for thyroid, lacto-, and horseradish peroxidases, respectively, whereas guaiacol oxidation peaked at pH 7.0-7.8 for all three enzymes. On the basis of these results and the dissimilar molecular sizes reported for trypsin-solubilized thyroid peroxidase by several other investigators, it was concluded that the molecular size is primarily determined by the conditions of proteolysis.", "contents": "Purification of bovine thyroid peroxidase. Trypsin-solubilized peroxidase activity from beef subcellular particles was resolved by DEAE-cellulose chromatography into 5 fractions, which contained enzymatically active components that ranged in molecular size from 73,000 to 340,000 daltons. The most active fraction (mol wt, 92,000 by gel filtration) was further purified (59,000-fold overall) by chromatography on hydroxylapatite. This highly purified peroxidase preparation had an absorbance purity ratio (A410:A280) of 0.55 and oxidized iodide (I3-formation) and guaiacol at rates of 300 and 460 micronmol/min/mg, respectively, which were about 3 and 1 1/2 times, respectively, greater than any previously described preparations. The enzyme was contaminated with an inactive protein of equal size. The highly purified peroxidase preparation lost its activity within a few days even when stored at -15 C with iodide. Two of the other DEAE-cellulose fractions contained peroxidase components with estimated sizes (gel filtration) of 73,000, 96,000, and 98,000, which were further purified purified (1,600 and 15,600 fold) on hydroxylapatite. They were 1/4 to 1/40 as active as the highly purified preparation and also became increasingly labile on purification. The remaining two DEAE-cellulose fractions were heterogeneous mixtures of stable peroxidase components whose average molecular sizes (gel filtration) were 220,000, 300,000, and 340,000 daltons, and which were not amenable to further purification on hydroxylapatite. The ratio of guaiacol to iodide activity decreased from 3.0 in the particles to about 1.5 in the highly purified preparations. The turnover numbers of the purest peroxidase component (mol wt. 92,000) for iodide and guaiacol were very similar to those of highly purifed, commericial lacto- and horseradish peroxidases. The pH maxima for iodide oxidation were 7.4, 6.0, and 4.5 for thyroid, lacto-, and horseradish peroxidases, respectively, whereas guaiacol oxidation peaked at pH 7.0-7.8 for all three enzymes. On the basis of these results and the dissimilar molecular sizes reported for trypsin-solubilized thyroid peroxidase by several other investigators, it was concluded that the molecular size is primarily determined by the conditions of proteolysis."}
{"id": "PMID:15823", "title": "Beta-adrenergic stimulation of cyclic AMP content and parathyroid hormone release from isolated bovine parathyroid cells.", "content": "The effects of beta-adrenergic agonists and antagonists on cyclic AMP (cAMP) accumulation and parathyroid hormone (PTH) release from isolated bovine parathyroid cells have been determined. Beta-adrenergic agonists markedly stimulate cAMP production and PTH release with an order of potency (-) isoproterenol greater than (-)epinephrine greater than greater than (-) norepinephrine, suggesting a beta2-type adrenergically mediated process. Both effects are blocked by the beta-blocker propranolol with the strict stereospecificity expected for a beta-adrenergic response. Low calcium concentrations also stimulate cAMP accumulation, but the cyclic nucleotide response under these conditions is only 3% of that obtained with isoproterenol, raising the possibility that factors other than cAMP may control low calcium-mediated PTH release. The release of PTH by low calcium is also not blocked by propranolol, confirming the independence of the response to low ambient calcium from the beta-adrenergic receptor. These studies substantiate further the utility of the isolated parathyroid cell preparation for studying secretagogue-mediated alterations in cyclic nucleotides and hormone secretion. Isolated cells also also make feasible the direct identification of beta-adrenergic receptors in parathyroid cell membranes and whole cells.", "contents": "Beta-adrenergic stimulation of cyclic AMP content and parathyroid hormone release from isolated bovine parathyroid cells. The effects of beta-adrenergic agonists and antagonists on cyclic AMP (cAMP) accumulation and parathyroid hormone (PTH) release from isolated bovine parathyroid cells have been determined. Beta-adrenergic agonists markedly stimulate cAMP production and PTH release with an order of potency (-) isoproterenol greater than (-)epinephrine greater than greater than (-) norepinephrine, suggesting a beta2-type adrenergically mediated process. Both effects are blocked by the beta-blocker propranolol with the strict stereospecificity expected for a beta-adrenergic response. Low calcium concentrations also stimulate cAMP accumulation, but the cyclic nucleotide response under these conditions is only 3% of that obtained with isoproterenol, raising the possibility that factors other than cAMP may control low calcium-mediated PTH release. The release of PTH by low calcium is also not blocked by propranolol, confirming the independence of the response to low ambient calcium from the beta-adrenergic receptor. These studies substantiate further the utility of the isolated parathyroid cell preparation for studying secretagogue-mediated alterations in cyclic nucleotides and hormone secretion. Isolated cells also also make feasible the direct identification of beta-adrenergic receptors in parathyroid cell membranes and whole cells."}
{"id": "PMID:15824", "title": "Direct identification of beta-adrenergic receptors on isolated bovine parathyroid cells.", "content": "The radioiodinated beta-blocker iodohydroxybenzylpindolol ([125I]HYP) has been used to identify directly and characterize beta-adrenergic receptors in isolated bovine parathyroid cells. [125I]HYP was bound rapidly and reversibly to isolated bovine parathyroid cell membranes. Scatchard analysis revealed a single class of binding sites with high affinity (4 X 10(10M-1) and low capacity (0.7 pmol/mg). Saturation analysis of [125I]HYP binding to intact bovine parathyroid cells suggested a site with similar affinity on whole cells and with a binding capacity of 5000-10,000 sites/cell. True dissociation constants (Kd's) for beta-adrenergic agonists and antagonists were in good agreement with activation constants (KA'S) and inhibition constants (KI'S) for effects on adenylate cyclase in membrane preparations. These constants also were in reasonable agreement with KA'S and KI'S previously shown for effects of agonists and antagonists on cAMP accumulation and PTH release in whole cells. This study shows by direct analysis that beta-adrenergic receptors exist on isolated bovine parathyroid cells, and that there is close coupling between receptor binding, effects on cAMP and hormonal release. This represents still another system in which [125I]HYP has been successfully used to study beta adrenergic receptors in membrane as well as intact cell preparations.", "contents": "Direct identification of beta-adrenergic receptors on isolated bovine parathyroid cells. The radioiodinated beta-blocker iodohydroxybenzylpindolol ([125I]HYP) has been used to identify directly and characterize beta-adrenergic receptors in isolated bovine parathyroid cells. [125I]HYP was bound rapidly and reversibly to isolated bovine parathyroid cell membranes. Scatchard analysis revealed a single class of binding sites with high affinity (4 X 10(10M-1) and low capacity (0.7 pmol/mg). Saturation analysis of [125I]HYP binding to intact bovine parathyroid cells suggested a site with similar affinity on whole cells and with a binding capacity of 5000-10,000 sites/cell. True dissociation constants (Kd's) for beta-adrenergic agonists and antagonists were in good agreement with activation constants (KA'S) and inhibition constants (KI'S) for effects on adenylate cyclase in membrane preparations. These constants also were in reasonable agreement with KA'S and KI'S previously shown for effects of agonists and antagonists on cAMP accumulation and PTH release in whole cells. This study shows by direct analysis that beta-adrenergic receptors exist on isolated bovine parathyroid cells, and that there is close coupling between receptor binding, effects on cAMP and hormonal release. This represents still another system in which [125I]HYP has been successfully used to study beta adrenergic receptors in membrane as well as intact cell preparations."}
{"id": "PMID:15825", "title": "[Testosterone reserve capacity in prepubertal and juvenile testes after sugery for undescended testis].", "content": "Tests testosterone reserve capacity of 6--15 year-old boys was estimated after operative correction of testicular maldescensus by a maximal stimulation test. Subnormal plasma testosterone levels were found in only 2 out of 14 patients with bilateral and 4 with unilateral orchidopexy. Prepubertal boys with unilateral anorchia had normal basal testosterone values and a normal testosterone rise after stimulation. In prepubertal boys with bilateral testes atrophy there was observed a diminished rise after stimulation. The basal testosterone levels were normal. The testosterone basal levels of pubertal boys with unilateral anorchia or bilateral atrophy were subnormal and the stimuation of testosterone production was reduced. The testicular volume of patients without atrophy or anorchia after orchidopexy was normal in prepuberty. During puberta a progressive relative decrease of the testicular volume was observed as compared to normal development. In conclusion, the results demonstrate that the endocrine function in most patients with unilateral or bilateral orchidopexy is in the normal range--a regular puberty can be expected.", "contents": "[Testosterone reserve capacity in prepubertal and juvenile testes after sugery for undescended testis]. Tests testosterone reserve capacity of 6--15 year-old boys was estimated after operative correction of testicular maldescensus by a maximal stimulation test. Subnormal plasma testosterone levels were found in only 2 out of 14 patients with bilateral and 4 with unilateral orchidopexy. Prepubertal boys with unilateral anorchia had normal basal testosterone values and a normal testosterone rise after stimulation. In prepubertal boys with bilateral testes atrophy there was observed a diminished rise after stimulation. The basal testosterone levels were normal. The testosterone basal levels of pubertal boys with unilateral anorchia or bilateral atrophy were subnormal and the stimuation of testosterone production was reduced. The testicular volume of patients without atrophy or anorchia after orchidopexy was normal in prepuberty. During puberta a progressive relative decrease of the testicular volume was observed as compared to normal development. In conclusion, the results demonstrate that the endocrine function in most patients with unilateral or bilateral orchidopexy is in the normal range--a regular puberty can be expected."}
{"id": "PMID:15826", "title": "Estimation of pregnenolone synthesis in rat adrenal homogenates: some cofactor requirements: effects of stress, hypophysectomy, cortisone and ACTH.", "content": "Pregnenolone synthesis was estimated in whole adrenal homogenates incubated in the presence of cyanoketone (2alpha-cyano-4,4,17alpha-trimethyl-androst-5-en-17beta-ol-3-one). The yield of pregnenolone depended on the type of incubation medium employed. Both Ca++ and bovine serum albumin (BSA) markedly stimulated the rate of pregnenolone synthesis as did  NADPH or NADPH generating system. Aminoglutethimide added in vitro inhibited cholesterol sidechain cleavage activity. Ether stress in vivo stimulated pregnenolone synthesis in vitro, and hypophysectomy of 24 hours duration resulted in a decrease. Cortisone administration for 8 days reduced the formation of pregnenolone by rat adrenal homogenates, an effect prevented by concomitant treatment with ACTH. Similarly, hypophysectomy of 8 days duration resulted in a marked diminution of pregnenolone synthesis and ACTH replacement reversed this effect. Changes in pregnenolone synthesis were paralleled by changes in corticosterone and total steroid production.", "contents": "Estimation of pregnenolone synthesis in rat adrenal homogenates: some cofactor requirements: effects of stress, hypophysectomy, cortisone and ACTH. Pregnenolone synthesis was estimated in whole adrenal homogenates incubated in the presence of cyanoketone (2alpha-cyano-4,4,17alpha-trimethyl-androst-5-en-17beta-ol-3-one). The yield of pregnenolone depended on the type of incubation medium employed. Both Ca++ and bovine serum albumin (BSA) markedly stimulated the rate of pregnenolone synthesis as did  NADPH or NADPH generating system. Aminoglutethimide added in vitro inhibited cholesterol sidechain cleavage activity. Ether stress in vivo stimulated pregnenolone synthesis in vitro, and hypophysectomy of 24 hours duration resulted in a decrease. Cortisone administration for 8 days reduced the formation of pregnenolone by rat adrenal homogenates, an effect prevented by concomitant treatment with ACTH. Similarly, hypophysectomy of 8 days duration resulted in a marked diminution of pregnenolone synthesis and ACTH replacement reversed this effect. Changes in pregnenolone synthesis were paralleled by changes in corticosterone and total steroid production."}
{"id": "PMID:15827", "title": "The effect of repeated immobilization on the level of plasma corticosterone and on the activity of several liver enzymes in rats.", "content": "The effect of repeated stress on the level  of plasma corticosterone and on the activity of several target enzymes for this hormone in the liver was studied. In adult male rats immobilized for 2.5 hrs daily, on day 7 the response of both plasma corticosterone and hepatic tyrosine aminotransferase is modified: After similar increases immediately after immobilization as in aminals stressed for the first time, in the conditioned rats precocious decreases to initial values take place. Moreover, on day 4, 24 hrs after a third immobilization, there are increases arise partly at least as a consequence of diminished food intake, as shown by comparing them with data from pair-fed rats. Partial fasting leading also to slight increase of hepatic glucose-6-phosphatase activity constitutes an  important part of repeated stress with substantial impacts on metabolic processes.", "contents": "The effect of repeated immobilization on the level of plasma corticosterone and on the activity of several liver enzymes in rats. The effect of repeated stress on the level  of plasma corticosterone and on the activity of several target enzymes for this hormone in the liver was studied. In adult male rats immobilized for 2.5 hrs daily, on day 7 the response of both plasma corticosterone and hepatic tyrosine aminotransferase is modified: After similar increases immediately after immobilization as in aminals stressed for the first time, in the conditioned rats precocious decreases to initial values take place. Moreover, on day 4, 24 hrs after a third immobilization, there are increases arise partly at least as a consequence of diminished food intake, as shown by comparing them with data from pair-fed rats. Partial fasting leading also to slight increase of hepatic glucose-6-phosphatase activity constitutes an  important part of repeated stress with substantial impacts on metabolic processes."}
{"id": "PMID:15828", "title": "Tyramine oxidase activity in needle biopsy of normal livers and diseased livers.", "content": "Tyramine oxidase and UDP-glucuronyl transferase activities were determined in 52 diseased livers obtained by needle biopsy. 14 liver specimens were also subjected to acetyl CoA carboxylase determination. Tyramine oxidase level was elevated in livers with nonalcoholic fatty change or toxic hepatitis, and reduced in livers with fibrosis or chronic alcoholic injury. UDP-glucuronyl transferase activity was reduced in livers with severe parenchymal damage or hyperbilirubinemia. Acetyl CoA carboxylase activity decreased markedly in an active alcoholic cirrhotic liver, and was elevated in alcoholic fatty livers as well as in a liver with acute venous stasis.", "contents": "Tyramine oxidase activity in needle biopsy of normal livers and diseased livers. Tyramine oxidase and UDP-glucuronyl transferase activities were determined in 52 diseased livers obtained by needle biopsy. 14 liver specimens were also subjected to acetyl CoA carboxylase determination. Tyramine oxidase level was elevated in livers with nonalcoholic fatty change or toxic hepatitis, and reduced in livers with fibrosis or chronic alcoholic injury. UDP-glucuronyl transferase activity was reduced in livers with severe parenchymal damage or hyperbilirubinemia. Acetyl CoA carboxylase activity decreased markedly in an active alcoholic cirrhotic liver, and was elevated in alcoholic fatty livers as well as in a liver with acute venous stasis."}
{"id": "PMID:15829", "title": "Interactions of divalent cations and nucleotides with solubilized cardiac guanylate cyclase.", "content": "Some properties of guanylate cyclase, which was solubilized from the rabbit heart washed particles by the treatment with Triton X-100, were investigated. The solubilized enzyme activity was stimulated by Mg2+ in the presence of low (subsaturating) Mn2+ (GTP is greater than Mn2+); under these conditions, Ga2+ was inhibitory. At subsaturating MnGTP and free Mn2+, the solubilized enzyme was markedly stimulated by MnGDP and MnATP; CaGTP on the other hand, was inhibitory. These results are consistent with the view that the particulate guanylate cyclase may exist in the cell as a metalloenzyme with tightly bound Mn2+ and that Mg2+ supports its catalysis while Ca2+ as well as nucleotides may exert regulatory effects on its activity.", "contents": "Interactions of divalent cations and nucleotides with solubilized cardiac guanylate cyclase. Some properties of guanylate cyclase, which was solubilized from the rabbit heart washed particles by the treatment with Triton X-100, were investigated. The solubilized enzyme activity was stimulated by Mg2+ in the presence of low (subsaturating) Mn2+ (GTP is greater than Mn2+); under these conditions, Ga2+ was inhibitory. At subsaturating MnGTP and free Mn2+, the solubilized enzyme was markedly stimulated by MnGDP and MnATP; CaGTP on the other hand, was inhibitory. These results are consistent with the view that the particulate guanylate cyclase may exist in the cell as a metalloenzyme with tightly bound Mn2+ and that Mg2+ supports its catalysis while Ca2+ as well as nucleotides may exert regulatory effects on its activity."}
{"id": "PMID:15830", "title": "Hepatic alkaline phosphatase isoenzymes: isolation, characterization and differential alteration.", "content": "Although it is generally believed that hepatic alkaline phosphatase is localized to liver plasma membranes, 63% is present in the cytosol fraction after ultracentrifugation of rat liver homogenates. Divalent cation requirements, heat inactivation, pH optima, Km and chemical inhibition characteristics of partially purified alkaline phosphatase enzymes prepared from membrane and cytosol fractions suggested different structural forms. Furthermore, bile duct obstruction and ethinyl estradiol administration preferentially increased membrane-bound alkaline phosphatase activity, while cytosol activity was unaltered. In contrast, phenobarbital treatment decreased membrane-bound alkaline phosphatase and increased cytosol activity. These studies support the presence of two forms of hepatic alkaline phosphatase in rat liver which are regulated by different control mechanisms.", "contents": "Hepatic alkaline phosphatase isoenzymes: isolation, characterization and differential alteration. Although it is generally believed that hepatic alkaline phosphatase is localized to liver plasma membranes, 63% is present in the cytosol fraction after ultracentrifugation of rat liver homogenates. Divalent cation requirements, heat inactivation, pH optima, Km and chemical inhibition characteristics of partially purified alkaline phosphatase enzymes prepared from membrane and cytosol fractions suggested different structural forms. Furthermore, bile duct obstruction and ethinyl estradiol administration preferentially increased membrane-bound alkaline phosphatase activity, while cytosol activity was unaltered. In contrast, phenobarbital treatment decreased membrane-bound alkaline phosphatase and increased cytosol activity. These studies support the presence of two forms of hepatic alkaline phosphatase in rat liver which are regulated by different control mechanisms."}
{"id": "PMID:15831", "title": "The interaction of phospholipid membranes and detergents with glutamate dehydrogenase.", "content": "1. The interaction of beef liver glutamate dehydrogenase with cardiolipin from both beef liver mitochondria and beef heart mitochondria, with phosphatidylcholine from both beef liver mitochondria and egg-yolk, and with beef brain phosphatidylserine was investigated by steady-state kinetic methods. 2. the phosphatidylcholine did not inhibit the enzyme under a wide range of conditions. The cardiolipins and phosphatidylserine inhibited the enzyme. The inhibition by these lipids was found to diminish with time if the lipids were prepared and the reaction was studied in either phosphate or Tris buffers, but in zwitterionic buffers these lipid brought about a rapid, reversible inhibition which remained stable with time for at least 150 min. 3. The kinetic type of the inhibition was difficult to determine because of variation between lipid sonicates. Complex mixed types of inhibition were found with cardiolipin, and with phosphatidylserine the inhibition approximated to a non-competitive interaction with Ki(app) values varying between (0.9-6.1) x 10(-6)M. 4. The extent of inhibition decreased with increasing pH  and with increasing ionic strength. Basic proteins, such as cytochrome c, show a higher affinity for the anionic membranes and can dissociate the enzyme-lipid complexes. Cosonicates of the cardiolipin and phosphatidylcholine inhibited the enzyme, the extent of inhibition increasing in proportion to the amount of acidic lipid. 5. Sodium dodecylsulphate causes a time-dependent inhibition of the enzyme. The kinetics of this effect and its variation with detergent concentration were studied. 6. The relationship of these observations to the structure and function of the enzyme is discussed. It is suggested that their apparent regulation of the enzyme by oestrogens and other small molecules is due to their binding in vitro at sites on the enzyme designed for binding cardiolipin, when the enzyme is functioning in vivo. The association of the enzyme oligomer in vitro may, for similar reasons, be an artifact.", "contents": "The interaction of phospholipid membranes and detergents with glutamate dehydrogenase. 1. The interaction of beef liver glutamate dehydrogenase with cardiolipin from both beef liver mitochondria and beef heart mitochondria, with phosphatidylcholine from both beef liver mitochondria and egg-yolk, and with beef brain phosphatidylserine was investigated by steady-state kinetic methods. 2. the phosphatidylcholine did not inhibit the enzyme under a wide range of conditions. The cardiolipins and phosphatidylserine inhibited the enzyme. The inhibition by these lipids was found to diminish with time if the lipids were prepared and the reaction was studied in either phosphate or Tris buffers, but in zwitterionic buffers these lipid brought about a rapid, reversible inhibition which remained stable with time for at least 150 min. 3. The kinetic type of the inhibition was difficult to determine because of variation between lipid sonicates. Complex mixed types of inhibition were found with cardiolipin, and with phosphatidylserine the inhibition approximated to a non-competitive interaction with Ki(app) values varying between (0.9-6.1) x 10(-6)M. 4. The extent of inhibition decreased with increasing pH  and with increasing ionic strength. Basic proteins, such as cytochrome c, show a higher affinity for the anionic membranes and can dissociate the enzyme-lipid complexes. Cosonicates of the cardiolipin and phosphatidylcholine inhibited the enzyme, the extent of inhibition increasing in proportion to the amount of acidic lipid. 5. Sodium dodecylsulphate causes a time-dependent inhibition of the enzyme. The kinetics of this effect and its variation with detergent concentration were studied. 6. The relationship of these observations to the structure and function of the enzyme is discussed. It is suggested that their apparent regulation of the enzyme by oestrogens and other small molecules is due to their binding in vitro at sites on the enzyme designed for binding cardiolipin, when the enzyme is functioning in vivo. The association of the enzyme oligomer in vitro may, for similar reasons, be an artifact."}
{"id": "PMID:15832", "title": "The interaction of phospholipid membranes and detergents with glutamate dehydrogenase.", "content": "1. Both the anionic detergent sodium dodecylsulphate and the cationic detergent cetyltrimethylammonium bromide quenched the protein fluorescence of glutamate dehydrogenase. The anionic compound was more effective and brought about 50% quenching at a detergent concentration of 0.4 mM. The zwitterionic amphiphile, lysolecithin, did not quench the protein fluorescence and neither did the short-chain detergent n-hexylsulphonate, which under the range of concentrations examined (less than 1 mM) does not form micelles. 2. The zwitterionic phospholipid, phosphatidylcholine, did not quench the protein fluorescence but the anionic phospholipids, phosphatidylserine and cardiolipin, induced a reversible quenching of the enzyme fluorescence. These observations confirm the specificity of the phospholipid-enzyme interactions as deduced from the kinetic studies of the preceding paper. The degree of quenching brought about by the phospholipids decreased with increasing ionic strength and increasing pH and could be substantially reduced by basic proteins. An electrostatic contribution to the interaction is inferred from these results. 3. The binding of the anionic phospholipids to the enzyme is manifested in a further enhancement of the fluorescence of a 1-anilinonaphthalene-8-sulphonate-enzyme complex. The presence of substrates and allosteric effectors affect the interaction of the lipids with the enzyme as indicated by the magnitude of this increase in fluorescence. The enhancement of fluorescence of NADH when bound to the enzyme was not affected by the binding of the lipids. 4. The complex formed between the enzyme and phosphatidylserine/phosphatidylcholine can be solubilized in isooctane. The photolability of the aqueous protein when subjected to irradiation at 280 nm is suppressed in the isooctane-soluble complex. 5. Phosphatidylserine brings about a rapid (t 1/2 is about 150 ms at a lipid concentration of 0.75 mM) dissociation of the linear aggregates formed between the enzyme oligomers. 6. A model of the enzyme-lipid-membrane complex, consistent with these results, is proposed. It is suggested that the enzyme is an allotopic protein and that the dissociation of the enzyme in vitro may involve binding sites on the protein which are designed for interaction with the cardiolipin of the inner mitochondrial membrane, when the enzyme is in the mitochondrial matrix.", "contents": "The interaction of phospholipid membranes and detergents with glutamate dehydrogenase. 1. Both the anionic detergent sodium dodecylsulphate and the cationic detergent cetyltrimethylammonium bromide quenched the protein fluorescence of glutamate dehydrogenase. The anionic compound was more effective and brought about 50% quenching at a detergent concentration of 0.4 mM. The zwitterionic amphiphile, lysolecithin, did not quench the protein fluorescence and neither did the short-chain detergent n-hexylsulphonate, which under the range of concentrations examined (less than 1 mM) does not form micelles. 2. The zwitterionic phospholipid, phosphatidylcholine, did not quench the protein fluorescence but the anionic phospholipids, phosphatidylserine and cardiolipin, induced a reversible quenching of the enzyme fluorescence. These observations confirm the specificity of the phospholipid-enzyme interactions as deduced from the kinetic studies of the preceding paper. The degree of quenching brought about by the phospholipids decreased with increasing ionic strength and increasing pH and could be substantially reduced by basic proteins. An electrostatic contribution to the interaction is inferred from these results. 3. The binding of the anionic phospholipids to the enzyme is manifested in a further enhancement of the fluorescence of a 1-anilinonaphthalene-8-sulphonate-enzyme complex. The presence of substrates and allosteric effectors affect the interaction of the lipids with the enzyme as indicated by the magnitude of this increase in fluorescence. The enhancement of fluorescence of NADH when bound to the enzyme was not affected by the binding of the lipids. 4. The complex formed between the enzyme and phosphatidylserine/phosphatidylcholine can be solubilized in isooctane. The photolability of the aqueous protein when subjected to irradiation at 280 nm is suppressed in the isooctane-soluble complex. 5. Phosphatidylserine brings about a rapid (t 1/2 is about 150 ms at a lipid concentration of 0.75 mM) dissociation of the linear aggregates formed between the enzyme oligomers. 6. A model of the enzyme-lipid-membrane complex, consistent with these results, is proposed. It is suggested that the enzyme is an allotopic protein and that the dissociation of the enzyme in vitro may involve binding sites on the protein which are designed for interaction with the cardiolipin of the inner mitochondrial membrane, when the enzyme is in the mitochondrial matrix."}
{"id": "PMID:15833", "title": "Purification and properties of pyrazon dioxygenase from pyrazon-degrading bacteria.", "content": "Chromatography on DEAE-cellulose and gel filtration on Sephadex revealed that pyrazon dioxygenase from pyrazon-degrading bacteria consists of three different enzyme components. No component alone oxidizes the phenyl moiety of pyrazon, only when the three components are combined can oxidation be detected. Following electron paramagnetic resonance and ultraviolet measurements the protein nature of the three components was determined: component A1 (molecular weight about 180000,red-brown in colour) is an iron-sulphur protein. The existence of approximately two moles of iron and two moles of inorganic sulphur per mole of protein was demonstrated. This enzyme component was purified to homogeneity in disc electrophoresis. Component A2 is a yellow protein of a molecular weight of about 67000. FAD was shown to be the prosthetic group of this protein. Component B (molecular weight about 12000, brown in colour) is a protein of the ferredoxin type, which was purified to homogeneity, as demonstrated by disc electrophoresis. A hypothetical scheme for the cooperation of the three components is proposed: component A2 accepts as cosubstrate NADH and functions as a ferredoxin reductase. The ferredoxin, component B, has the function of an electron carrier. The conversion of the substrates is effected by component A1, the terminal dioxygenase.", "contents": "Purification and properties of pyrazon dioxygenase from pyrazon-degrading bacteria. Chromatography on DEAE-cellulose and gel filtration on Sephadex revealed that pyrazon dioxygenase from pyrazon-degrading bacteria consists of three different enzyme components. No component alone oxidizes the phenyl moiety of pyrazon, only when the three components are combined can oxidation be detected. Following electron paramagnetic resonance and ultraviolet measurements the protein nature of the three components was determined: component A1 (molecular weight about 180000,red-brown in colour) is an iron-sulphur protein. The existence of approximately two moles of iron and two moles of inorganic sulphur per mole of protein was demonstrated. This enzyme component was purified to homogeneity in disc electrophoresis. Component A2 is a yellow protein of a molecular weight of about 67000. FAD was shown to be the prosthetic group of this protein. Component B (molecular weight about 12000, brown in colour) is a protein of the ferredoxin type, which was purified to homogeneity, as demonstrated by disc electrophoresis. A hypothetical scheme for the cooperation of the three components is proposed: component A2 accepts as cosubstrate NADH and functions as a ferredoxin reductase. The ferredoxin, component B, has the function of an electron carrier. The conversion of the substrates is effected by component A1, the terminal dioxygenase."}
{"id": "PMID:15834", "title": "Antibodies and autoantibodies of glycogen phosphorylase b: inactivation of pig and rabbit enzymes.", "content": "Pig skeletal muscle glycogen phosphorylase b was purified using ammonium sulfate fractionation, DEAE-Sephadex A-50 and Sephadex G-200 column chromatography. The purified enzyme was used to immunize rabbits in the presence or in the absence of complete Freund adjuvant. Antibodies against pig phosphorylase in pure form were isolated from rabbit antisera using insoluble immunoadsorbents of pig phosphorylase. Autoantibodies against the rabbit enzyme were obtained from the same antisera using insoluble immunoadsorbents of rabbit phosphorylase. Complete inactivation of pig phosphorylase was accomplished by an antibody/enzyme molar ratio equal to 4 and autoantibody/enzyme molar ratio equal to 130. Complete inactivation of rabbit phosphorylase was accomplished by an antibody/enzyme molar ratio equal to 250 and autoantibody/enzyme molar ratio equal to 160. Passive haemagglutination technique gave positive results with minimum amounts of 0.02 microng/ml and 0.8 microng/ml for pig and rabbit phosphorylase respectively. Kinetic experiments have shown that antibodies and autoantibodies act as noncompetitive inhibitors of both enzymes with respect to AMP and glucose 1-phosphate but exhibit a mixed type  of inhibition with respect to glycogen. When glycogen hydrolysates were used as substrate in place of intact glycogen molecules a pronounced decrease in the inhibitory capacity of antienzyme on the enzyme was demonstrated.", "contents": "Antibodies and autoantibodies of glycogen phosphorylase b: inactivation of pig and rabbit enzymes. Pig skeletal muscle glycogen phosphorylase b was purified using ammonium sulfate fractionation, DEAE-Sephadex A-50 and Sephadex G-200 column chromatography. The purified enzyme was used to immunize rabbits in the presence or in the absence of complete Freund adjuvant. Antibodies against pig phosphorylase in pure form were isolated from rabbit antisera using insoluble immunoadsorbents of pig phosphorylase. Autoantibodies against the rabbit enzyme were obtained from the same antisera using insoluble immunoadsorbents of rabbit phosphorylase. Complete inactivation of pig phosphorylase was accomplished by an antibody/enzyme molar ratio equal to 4 and autoantibody/enzyme molar ratio equal to 130. Complete inactivation of rabbit phosphorylase was accomplished by an antibody/enzyme molar ratio equal to 250 and autoantibody/enzyme molar ratio equal to 160. Passive haemagglutination technique gave positive results with minimum amounts of 0.02 microng/ml and 0.8 microng/ml for pig and rabbit phosphorylase respectively. Kinetic experiments have shown that antibodies and autoantibodies act as noncompetitive inhibitors of both enzymes with respect to AMP and glucose 1-phosphate but exhibit a mixed type  of inhibition with respect to glycogen. When glycogen hydrolysates were used as substrate in place of intact glycogen molecules a pronounced decrease in the inhibitory capacity of antienzyme on the enzyme was demonstrated."}
{"id": "PMID:15835", "title": "Cathepsin L. A new proteinase from rat-liver lysosomes.", "content": "1. Cathepsin L was purified from rat liver lysosomes by cell fractionation, osmotic disruption of the lysosomes in the lysosomal mitochondrial pellet, gel filtration of the lysosomal extract and chromatography on CM-Sephadex. 2. Cathepsin L is a thiol proteinase and exists in several multiple forms visible on the disc electropherogram. By polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate its molecular weight was found to be 23000-24000. The isoelectric points of the multiple forms of cathepsin L extended from pH 5.8-6.1 ascertained by analytical isoelectric focusing. 3. Using various protein substrates, cathepsin L was found to be the most active endopeptidase from rat liver lysosomes acting at pH 6-7. In contrast to cathepsin B1, its capability of hydrolyzing N-substituted derivatives of arginine is low and it does not split esters. 4. Greatest activity is obtained close to pH 5.0 with 70-90% of maximal activity at pH 4.0 and pH 6.0 and 30-40% at pH 7.0. 5. The enzyme is strongly inhibited by leupeptin and the chloromethyl ketone of tosyl-lysine. Leupeptin acts as a pseudo-irreversible inhibitor. 6. The enzyme is stable for several months at slightly acid pH values in the presence of thiol compounds in a deep-frozen state.", "contents": "Cathepsin L. A new proteinase from rat-liver lysosomes. 1. Cathepsin L was purified from rat liver lysosomes by cell fractionation, osmotic disruption of the lysosomes in the lysosomal mitochondrial pellet, gel filtration of the lysosomal extract and chromatography on CM-Sephadex. 2. Cathepsin L is a thiol proteinase and exists in several multiple forms visible on the disc electropherogram. By polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate its molecular weight was found to be 23000-24000. The isoelectric points of the multiple forms of cathepsin L extended from pH 5.8-6.1 ascertained by analytical isoelectric focusing. 3. Using various protein substrates, cathepsin L was found to be the most active endopeptidase from rat liver lysosomes acting at pH 6-7. In contrast to cathepsin B1, its capability of hydrolyzing N-substituted derivatives of arginine is low and it does not split esters. 4. Greatest activity is obtained close to pH 5.0 with 70-90% of maximal activity at pH 4.0 and pH 6.0 and 30-40% at pH 7.0. 5. The enzyme is strongly inhibited by leupeptin and the chloromethyl ketone of tosyl-lysine. Leupeptin acts as a pseudo-irreversible inhibitor. 6. The enzyme is stable for several months at slightly acid pH values in the presence of thiol compounds in a deep-frozen state."}
{"id": "PMID:15836", "title": "Anabolic ornithine carbamolytransferase of Pseudomonas. The bases of its functional specialization.", "content": "The anabolic ornithine carbamoyltransferase of Pseudomonas appears to be extremely specialized. Unlike the other carbamoyltransferases studied, this enzyme catalyzes the phosphorolytic cleavage of citrulline with a very poor efficiency. The main goal of this paper is to understand what, in the catalytic process, causes this directed functional specialization. On the basis of kinetic data and thermodynamic properties of the reaction, it appears that the reaction mechanism is the same as for ornithine carbamoyltransferases from other sources, that is, of the sequential ordered type, where carbamoylphosphate is the first substrate to be bound and phosphate the last product to be released. In addition to this, and here lies the difference with other ornithine carbamoyltransferases, the anabolic transferase of Pseudomonas forms a binary dead-end complex with citrulline, leading to inefficient binding of phosphate and citrulline to the enzyme. Therefore the phosphorolytic cleavage of citrulline is equally inefficient. It should be mentioned that the affinity of the enzyme for citrulline at its catalytic site is low as compared to other transferases.", "contents": "Anabolic ornithine carbamolytransferase of Pseudomonas. The bases of its functional specialization. The anabolic ornithine carbamoyltransferase of Pseudomonas appears to be extremely specialized. Unlike the other carbamoyltransferases studied, this enzyme catalyzes the phosphorolytic cleavage of citrulline with a very poor efficiency. The main goal of this paper is to understand what, in the catalytic process, causes this directed functional specialization. On the basis of kinetic data and thermodynamic properties of the reaction, it appears that the reaction mechanism is the same as for ornithine carbamoyltransferases from other sources, that is, of the sequential ordered type, where carbamoylphosphate is the first substrate to be bound and phosphate the last product to be released. In addition to this, and here lies the difference with other ornithine carbamoyltransferases, the anabolic transferase of Pseudomonas forms a binary dead-end complex with citrulline, leading to inefficient binding of phosphate and citrulline to the enzyme. Therefore the phosphorolytic cleavage of citrulline is equally inefficient. It should be mentioned that the affinity of the enzyme for citrulline at its catalytic site is low as compared to other transferases."}
{"id": "PMID:15837", "title": "The kinetics of reoxidation of reduced benzylamine oxidase.", "content": "1. The mechanism of reoxidation of reduced benzylamine oxidase has been investigated at different pH between 6 and 10 by steady-state and transient-state kinetic methods. 2. The reoxidation process involves minimally a second-order interaction between reduced enzyme and oxygen leading to the formation of a spectrally modified enzyme intermediate, and a subsequent first-order step converting this intermediate into free enzyme. The variation with pH of rate constants according to such a reaction scheme is reported. 3. Under aerobic conditions the oxygen-independent reaction represents the main rate-limiting step in the catalytic process at alkaline pH. At neutral or acid pH the interaction between reduced enzyme and oxygen becomes mainly rate-limiting, indicating that the concentration of oxygen may be a critical factor controlling enzyme activity under physiological conditions. 4. The spectrally modified intermediate formed during the reoxidation process exhibits a difference-absorption band centered around 290 nm in comparison to free enzyme, and an additional difference-absorption band at 470 nm in comparison to reduced enzyme. These data indicate that formation of the intermediate, besides leading to a reappearance of the 470-nm absorption band disappearing on reduction of the enzyme, results in a spectral perturbation of one or several aromatic amino-acid residues in the protein. This perturbation could possibly reflect a conformational change of the enzymes.", "contents": "The kinetics of reoxidation of reduced benzylamine oxidase. 1. The mechanism of reoxidation of reduced benzylamine oxidase has been investigated at different pH between 6 and 10 by steady-state and transient-state kinetic methods. 2. The reoxidation process involves minimally a second-order interaction between reduced enzyme and oxygen leading to the formation of a spectrally modified enzyme intermediate, and a subsequent first-order step converting this intermediate into free enzyme. The variation with pH of rate constants according to such a reaction scheme is reported. 3. Under aerobic conditions the oxygen-independent reaction represents the main rate-limiting step in the catalytic process at alkaline pH. At neutral or acid pH the interaction between reduced enzyme and oxygen becomes mainly rate-limiting, indicating that the concentration of oxygen may be a critical factor controlling enzyme activity under physiological conditions. 4. The spectrally modified intermediate formed during the reoxidation process exhibits a difference-absorption band centered around 290 nm in comparison to free enzyme, and an additional difference-absorption band at 470 nm in comparison to reduced enzyme. These data indicate that formation of the intermediate, besides leading to a reappearance of the 470-nm absorption band disappearing on reduction of the enzyme, results in a spectral perturbation of one or several aromatic amino-acid residues in the protein. This perturbation could possibly reflect a conformational change of the enzymes."}
{"id": "PMID:15838", "title": "Studies of glutamate dehydrogenase. Methionine-169: the preferentially carboxymethylated residue.", "content": "In phosphate buffer at pH 7.0, 5,5'-dithio-bis(2-nitrobenzoic acid), N-ethylmaleimide or iodoacetamide do not alter the activity of beef liver glutamate dehydrogenase. Iodoacetate, however, inactivities the enzyme irreversibility by alkylation. Combined addition of the coenzyme NADH and the substrate 2-oxoglutarate or the effector GTP protects against this inactivation. The alkylation reaction is independent of pH between pH 6-9 indicating that amino, imidazole or phenolic groups are probably not involved in this reaction. Titration of the thiol groups, after denaturation of the enzyme, revealed the loss of approximately one group per polypeptide chain. However, this is not due to the exclusive alkylation of a cysteine residue, since alkylation with iodo-[2-14C]acetic acid also labels a methionine residue. 50% of the label is incorporated into methionine-169 and only 7% into cysteine-115, the remaining radioactivity is distributed in minor quantities (4%) in several unidentified residues. A probable cause of the erroneous thiol groups titration is discussed.", "contents": "Studies of glutamate dehydrogenase. Methionine-169: the preferentially carboxymethylated residue. In phosphate buffer at pH 7.0, 5,5'-dithio-bis(2-nitrobenzoic acid), N-ethylmaleimide or iodoacetamide do not alter the activity of beef liver glutamate dehydrogenase. Iodoacetate, however, inactivities the enzyme irreversibility by alkylation. Combined addition of the coenzyme NADH and the substrate 2-oxoglutarate or the effector GTP protects against this inactivation. The alkylation reaction is independent of pH between pH 6-9 indicating that amino, imidazole or phenolic groups are probably not involved in this reaction. Titration of the thiol groups, after denaturation of the enzyme, revealed the loss of approximately one group per polypeptide chain. However, this is not due to the exclusive alkylation of a cysteine residue, since alkylation with iodo-[2-14C]acetic acid also labels a methionine residue. 50% of the label is incorporated into methionine-169 and only 7% into cysteine-115, the remaining radioactivity is distributed in minor quantities (4%) in several unidentified residues. A probable cause of the erroneous thiol groups titration is discussed."}
{"id": "PMID:15839", "title": "Structural studies on periodate-oxidized chicken ovomucoid. Spectral behaviour of the tyrosine residues.", "content": "About 50% of the carbohydrate moiety of ovomucoid was destroyed by periodate oxidation. The oxidation was carried out for 6 h or 24 h. The data obtained showed that in the carbohydrate chain 2-5 glucosamines and 1-2 neutral sugar residues were decomposed with the consumption of 16 mol and 29 mol of periodate respectively. Periodic oxidation slightly changed the inhibitory activity of the ovomucoid, but altered its spectral properties. An increase of the absorption maximum at 278 nm was noted, as well as a tendency for normalization of phenolic ionization and an increase of the relative fluorescence. The reactivity of tyrosine residues towards tetranitromethane is also changed. It was suggested that even in native ovomucoid the tyrosines could be regarded as 'dissolved' in the 'carbohydrate solvent'. This contact could be achieved by the hydrogen bonds in the formation of which the NHCOCH3 groups of the glucosamine residues play an essential role. Peroxidate oxidation seems to lead to an alteration of the nature of the 'sugar solvent' and disturbs the conformation of the sugar chain.", "contents": "Structural studies on periodate-oxidized chicken ovomucoid. Spectral behaviour of the tyrosine residues. About 50% of the carbohydrate moiety of ovomucoid was destroyed by periodate oxidation. The oxidation was carried out for 6 h or 24 h. The data obtained showed that in the carbohydrate chain 2-5 glucosamines and 1-2 neutral sugar residues were decomposed with the consumption of 16 mol and 29 mol of periodate respectively. Periodic oxidation slightly changed the inhibitory activity of the ovomucoid, but altered its spectral properties. An increase of the absorption maximum at 278 nm was noted, as well as a tendency for normalization of phenolic ionization and an increase of the relative fluorescence. The reactivity of tyrosine residues towards tetranitromethane is also changed. It was suggested that even in native ovomucoid the tyrosines could be regarded as 'dissolved' in the 'carbohydrate solvent'. This contact could be achieved by the hydrogen bonds in the formation of which the NHCOCH3 groups of the glucosamine residues play an essential role. Peroxidate oxidation seems to lead to an alteration of the nature of the 'sugar solvent' and disturbs the conformation of the sugar chain."}
{"id": "PMID:15840", "title": "The purification and properties of NADP-dependent isocitrate dehydrogenase from ox-heart mitochondria.", "content": "The purification of NADP-linked isocitrate dehydrogenase from ox heart mitochondria is described. The molecular weight from gel filtration, sedimentation equilibrium and gel electrophoresis is 90000+/-4000, and there are two subunits in the molecule each of which binds NADPH with enhancement of the coenzyme fluorescence. The amino-acid composition is reported, and the absorption coefficient, A1/280%, estimated from dry weight measurements is 11.8 cm-1.", "contents": "The purification and properties of NADP-dependent isocitrate dehydrogenase from ox-heart mitochondria. The purification of NADP-linked isocitrate dehydrogenase from ox heart mitochondria is described. The molecular weight from gel filtration, sedimentation equilibrium and gel electrophoresis is 90000+/-4000, and there are two subunits in the molecule each of which binds NADPH with enhancement of the coenzyme fluorescence. The amino-acid composition is reported, and the absorption coefficient, A1/280%, estimated from dry weight measurements is 11.8 cm-1."}
{"id": "PMID:15841", "title": "Glycosaminoglycans and glycoproteins in metachromatic leucodystrophy.", "content": "A study is reported of the brain glycoproteins and the glycosaminoglycans in a case of infantile metachromatic leucodystrophy, associated with a ponto-cerebellar systemic atrophy, verified by autopsy. The glycosaminoglycan concentrations in the grey matter were within the normal range, while in the white matter they were slightly increased. The glycopeptides from the soluble and insoluble glycoproteins of white matter were altered not only in their quantity but also in their composition. In the grey matter a decrease of all sugars except the NaNa was detected in the insoluble fraction while in the soluble no change was detected, except for a threefold increase of fucose. The relationship was discussed of soluble to insoluble glycoproteins, and a mechanism for their derangement in MLD was suggested.", "contents": "Glycosaminoglycans and glycoproteins in metachromatic leucodystrophy. A study is reported of the brain glycoproteins and the glycosaminoglycans in a case of infantile metachromatic leucodystrophy, associated with a ponto-cerebellar systemic atrophy, verified by autopsy. The glycosaminoglycan concentrations in the grey matter were within the normal range, while in the white matter they were slightly increased. The glycopeptides from the soluble and insoluble glycoproteins of white matter were altered not only in their quantity but also in their composition. In the grey matter a decrease of all sugars except the NaNa was detected in the insoluble fraction while in the soluble no change was detected, except for a threefold increase of fucose. The relationship was discussed of soluble to insoluble glycoproteins, and a mechanism for their derangement in MLD was suggested."}
{"id": "PMID:15842", "title": "Prolongation of rat renal allograft survival by cyclophosphamide and intravenous donor-specific antigens.", "content": "Specific immunological hyporeactivity to Ag-B incompatible rat renal allografts was achieved after pretreatment of the recipients with donor strain platelets or spleen cells and cyclophosphamide (CY). The longest survival times were observed in animals pretreated with a single 75 mg/kg dose of CY together with 2 X 10(10) donor strain platelets or 2.5 X 10(9) spleen cells intravenously, 2 weeks prior to kidney transplant (median survival time, 71 and 47 days, respectively, compared to 12 days in untreated rats). CY or antigen given alone were ineffective. Anti-donor antibody activiy was routinely detectable in graft-bearing animals. Cell-mediated anti-donor immunity, although impaired, was still present in long-term survivors. These findings suggest that preservation of graft function and prolonged survival in antigen-CY-pretreated animals may be abetted by a combination of mechanisms including antigen-induced immunological enhancement, and deletion by CY of potentially reactive lymphoid cell clones. The use of CY in conjunction with donor antigen pretreatment may provide an additional increment of specific immunosuppression in clinical organ transplantation.", "contents": "Prolongation of rat renal allograft survival by cyclophosphamide and intravenous donor-specific antigens. Specific immunological hyporeactivity to Ag-B incompatible rat renal allografts was achieved after pretreatment of the recipients with donor strain platelets or spleen cells and cyclophosphamide (CY). The longest survival times were observed in animals pretreated with a single 75 mg/kg dose of CY together with 2 X 10(10) donor strain platelets or 2.5 X 10(9) spleen cells intravenously, 2 weeks prior to kidney transplant (median survival time, 71 and 47 days, respectively, compared to 12 days in untreated rats). CY or antigen given alone were ineffective. Anti-donor antibody activiy was routinely detectable in graft-bearing animals. Cell-mediated anti-donor immunity, although impaired, was still present in long-term survivors. These findings suggest that preservation of graft function and prolonged survival in antigen-CY-pretreated animals may be abetted by a combination of mechanisms including antigen-induced immunological enhancement, and deletion by CY of potentially reactive lymphoid cell clones. The use of CY in conjunction with donor antigen pretreatment may provide an additional increment of specific immunosuppression in clinical organ transplantation."}
{"id": "PMID:15843", "title": "Stress and cardiovascular disease.", "content": "Currently the role of stress as a potential factor in cardiovascular disease is receiving considerable attention. Accordingly, it is important to know how it is defined and identified, how it affects the cardiovascular system and how it can be managed with the knowledge presently available. An overview of the present body of knowledge on the relationship between stress and cardiovascular disease is presented for the reader's consideration.", "contents": "Stress and cardiovascular disease. Currently the role of stress as a potential factor in cardiovascular disease is receiving considerable attention. Accordingly, it is important to know how it is defined and identified, how it affects the cardiovascular system and how it can be managed with the knowledge presently available. An overview of the present body of knowledge on the relationship between stress and cardiovascular disease is presented for the reader's consideration."}
{"id": "PMID:15844", "title": "Alterations of lipid metabolism in healthy volunteers during long-term ethanol intake.", "content": "Nine young, healthy male volunteers were given ethanol (75 g/day) for 5 weeks. The ethanol was divided into five daily doses and taken so that blood ethanol levels never exceeded 0.04% (w/v). During the latter part of the ethanol intake period, there was a significant, transient increase of plasma triglyceride (TG) concentrations followed by reduction to normal levels. A three-fold increase of lipoprotein lipase activity (LLA) occurred in biopsy specimens of adipose tissue. An increase of alpha-lipoprotein concentrations, which correlated significantly with the decrease in plasma TG levels and the increase in adipose LLA, was also observed during the ethanol intake period. No changes were observed in plasma cholesterol and beta-lipoprotein levels. A transient, three-fold increase of TG concentrations occurred in liver biopsy specimens. Ultrastructural and cytochemical examinations of the biopsy specimens showed hyperplasia of the smooth endoplasmic reticulum, and increased canallicular activity of gamma-glutamyl transferase (gamma-GT) activity in most subjects towards the end of and after the ethanol intake period. Serum gamma-GT levels also increased significantly.", "contents": "Alterations of lipid metabolism in healthy volunteers during long-term ethanol intake. Nine young, healthy male volunteers were given ethanol (75 g/day) for 5 weeks. The ethanol was divided into five daily doses and taken so that blood ethanol levels never exceeded 0.04% (w/v). During the latter part of the ethanol intake period, there was a significant, transient increase of plasma triglyceride (TG) concentrations followed by reduction to normal levels. A three-fold increase of lipoprotein lipase activity (LLA) occurred in biopsy specimens of adipose tissue. An increase of alpha-lipoprotein concentrations, which correlated significantly with the decrease in plasma TG levels and the increase in adipose LLA, was also observed during the ethanol intake period. No changes were observed in plasma cholesterol and beta-lipoprotein levels. A transient, three-fold increase of TG concentrations occurred in liver biopsy specimens. Ultrastructural and cytochemical examinations of the biopsy specimens showed hyperplasia of the smooth endoplasmic reticulum, and increased canallicular activity of gamma-glutamyl transferase (gamma-GT) activity in most subjects towards the end of and after the ethanol intake period. Serum gamma-GT levels also increased significantly."}
{"id": "PMID:15845", "title": "Plasma concentrations, bioavailability and dissolution of chlorpropamide.", "content": "The bioavailability of chlorpropamide from two new formulations (Melitase tablets) has been compared to that from a reference formulation which is currently in clinical use as a hypoglycaemic agent. In both rate and extent of bioavailability, all three formulations may be considered equivalent, providing allowances are made for differences in drug content. With 95% confidence, the mean bioavailability of chlorpropamide from the new formulations was within about 16% of the mean from the reference formulaion, and formulation-related differences were not statistically significant. Although all three formulations were shown to have similar dissolution  profiles, dissolution of chlorpropamide was pH-dependent in vitro. Dissolution was almost complete during 30 min at pH 7.2, but only 40%-60% had dissolved during 90 min at pH 2.0. A peak mean concentration of 22.7 mug/ml was reached 3 h after administration of 2 x 100 mg tablets of the new formulation and peak mean concentrations of 26.8 mug/ml and 27.4 mug/ml were reached 3 h and 4 hours after administration of one 250 mg tablet of the new formulation and one 250 mg tablet of the reference formulation respectively. Formulation-related differences of mean plasma concentrations (after scaling for equal doses of 250mg) were not significant and each formulation provided similar plasma concentrations at corresponding times after administration. Statistically significant subject-related differences in all the parameters of bioavailability were shown by analyses of variance.", "contents": "Plasma concentrations, bioavailability and dissolution of chlorpropamide. The bioavailability of chlorpropamide from two new formulations (Melitase tablets) has been compared to that from a reference formulation which is currently in clinical use as a hypoglycaemic agent. In both rate and extent of bioavailability, all three formulations may be considered equivalent, providing allowances are made for differences in drug content. With 95% confidence, the mean bioavailability of chlorpropamide from the new formulations was within about 16% of the mean from the reference formulaion, and formulation-related differences were not statistically significant. Although all three formulations were shown to have similar dissolution  profiles, dissolution of chlorpropamide was pH-dependent in vitro. Dissolution was almost complete during 30 min at pH 7.2, but only 40%-60% had dissolved during 90 min at pH 2.0. A peak mean concentration of 22.7 mug/ml was reached 3 h after administration of 2 x 100 mg tablets of the new formulation and peak mean concentrations of 26.8 mug/ml and 27.4 mug/ml were reached 3 h and 4 hours after administration of one 250 mg tablet of the new formulation and one 250 mg tablet of the reference formulation respectively. Formulation-related differences of mean plasma concentrations (after scaling for equal doses of 250mg) were not significant and each formulation provided similar plasma concentrations at corresponding times after administration. Statistically significant subject-related differences in all the parameters of bioavailability were shown by analyses of variance."}
{"id": "PMID:15846", "title": "Tachyphylaxis to beta-adrenoceptor agonists in guinea pig airway smooth muscle in vivo and in vitro.", "content": "Beta-Adrenoceptor tachyphylaxis was induced by incubating spirally cut guinea pig tracheas with isoproterenol (2.4 x 10(-7) M) for 20 min. This incubation reduced the relaxant effects of catecholamines but not of dibutyryl cyclic AMP, theophylline or sodium nitrite. Tracheas incubated with norepinephrine, phosphodiesterase inhibitors or cyclic nucleotides became tachyphylactic to isoproterenol. Pretreatment with indomethacin prevented induction of tachyphylaxis. Incubation with adenosine, methoxamine or sodium nitrite did not induce beta-adrenoceptor tachyphylaxis. When we gave isoproterenol intramuscularly to guinea pigs, airway sensitivity to aerosolized histamine was unchanged but the toxicity of parenterally administered histamine was increased. A prolonged treatment with isoproterenol reduced airway sensitivity to histamine aerosols; this reduced sensitivity was reversed by indomethacin. Thus, beta-adrenoceptor tachyphylaxis may not explain increased toxicity of parenteral histamine after isoproterenol treatment. Elevated levels of cyclic AMP and an increased synthesis of prostaglandins may result in diminished response to beta-receptor stimulation.", "contents": "Tachyphylaxis to beta-adrenoceptor agonists in guinea pig airway smooth muscle in vivo and in vitro. Beta-Adrenoceptor tachyphylaxis was induced by incubating spirally cut guinea pig tracheas with isoproterenol (2.4 x 10(-7) M) for 20 min. This incubation reduced the relaxant effects of catecholamines but not of dibutyryl cyclic AMP, theophylline or sodium nitrite. Tracheas incubated with norepinephrine, phosphodiesterase inhibitors or cyclic nucleotides became tachyphylactic to isoproterenol. Pretreatment with indomethacin prevented induction of tachyphylaxis. Incubation with adenosine, methoxamine or sodium nitrite did not induce beta-adrenoceptor tachyphylaxis. When we gave isoproterenol intramuscularly to guinea pigs, airway sensitivity to aerosolized histamine was unchanged but the toxicity of parenterally administered histamine was increased. A prolonged treatment with isoproterenol reduced airway sensitivity to histamine aerosols; this reduced sensitivity was reversed by indomethacin. Thus, beta-adrenoceptor tachyphylaxis may not explain increased toxicity of parenteral histamine after isoproterenol treatment. Elevated levels of cyclic AMP and an increased synthesis of prostaglandins may result in diminished response to beta-receptor stimulation."}
{"id": "PMID:15847", "title": "Effect of neurohumoral modulators on the morphine-induced hyperthermia in non-tolerant rats.", "content": "Wistar rats from one supplier have been shown to exhibit the atypical body temperature responses to morphine. In contrast to commonly used rats, in which morphine induced dose-dependent changes in body temperature, the initial administration of morphine (5, 10, 20, and 40 mg/kg, s.c.) to rats of this particular strain produced a consistent and prominent hyperthermia. This hyperthermia is mediated via an action on the typical morphine receptors since it was completely prevented by a specific narcotic antagonist, naloxone. Effects of neurohumoral modulators on the hyperthermia have been investigated in these rats. Pretreatment of animals with p-chlorophenylalanine, alpha-methyltyrosine, phenoxybenzamine or propranolol did not alter the hyperthermia. In contrast, the s.c. administration of 1 mg/kg of either tertiary or quaternary anticholinergic drug such as scopolamine, atrophine, methscopolamine and methylatropine significantly inhibited the hyperthermia. These results suggest that morphine causes  hyperthermia in some strains of rats by a cholinergic mechanism and the involvement of an adrenergic or serotonergic mechanism in this case appears unlikely.", "contents": "Effect of neurohumoral modulators on the morphine-induced hyperthermia in non-tolerant rats. Wistar rats from one supplier have been shown to exhibit the atypical body temperature responses to morphine. In contrast to commonly used rats, in which morphine induced dose-dependent changes in body temperature, the initial administration of morphine (5, 10, 20, and 40 mg/kg, s.c.) to rats of this particular strain produced a consistent and prominent hyperthermia. This hyperthermia is mediated via an action on the typical morphine receptors since it was completely prevented by a specific narcotic antagonist, naloxone. Effects of neurohumoral modulators on the hyperthermia have been investigated in these rats. Pretreatment of animals with p-chlorophenylalanine, alpha-methyltyrosine, phenoxybenzamine or propranolol did not alter the hyperthermia. In contrast, the s.c. administration of 1 mg/kg of either tertiary or quaternary anticholinergic drug such as scopolamine, atrophine, methscopolamine and methylatropine significantly inhibited the hyperthermia. These results suggest that morphine causes  hyperthermia in some strains of rats by a cholinergic mechanism and the involvement of an adrenergic or serotonergic mechanism in this case appears unlikely."}
{"id": "PMID:15848", "title": "Induction of tolerance and withdrawal in rats receiving morphine in the spinal subarachnoid space.", "content": "Rats implanted with chronic catheters in the spinal subarachnoid space were given twice daily injections for 7 days of morphine sulfate, either intrathecally into the lumbar subarachnoid space (15 or 50 microng) or i.p. (20 mg/kg). The development of tolerance, as manifested in a reduction of the analgetic efficacy of these injections on the hot plate and tail flick, occurred in a dose dependent fashion over a period of 7 days. At this time, injections of i.p. morphine into animals which had received spinal morphine and vice versa revealed the existence of a two way cross tolerance between spinal and systemically administered morphine. Injection of naloxone into the spinal cord of animals exposed to i.p. morphine or conversely, i.p. naloxone in animals tolerant to intrathecal morphine, yielded a hyperreflexia and extreme sensitivity to handling. Other signs commonly observed in percipitated withdrawal, however, such as wet shakes and weight loss, were not observed.", "contents": "Induction of tolerance and withdrawal in rats receiving morphine in the spinal subarachnoid space. Rats implanted with chronic catheters in the spinal subarachnoid space were given twice daily injections for 7 days of morphine sulfate, either intrathecally into the lumbar subarachnoid space (15 or 50 microng) or i.p. (20 mg/kg). The development of tolerance, as manifested in a reduction of the analgetic efficacy of these injections on the hot plate and tail flick, occurred in a dose dependent fashion over a period of 7 days. At this time, injections of i.p. morphine into animals which had received spinal morphine and vice versa revealed the existence of a two way cross tolerance between spinal and systemically administered morphine. Injection of naloxone into the spinal cord of animals exposed to i.p. morphine or conversely, i.p. naloxone in animals tolerant to intrathecal morphine, yielded a hyperreflexia and extreme sensitivity to handling. Other signs commonly observed in percipitated withdrawal, however, such as wet shakes and weight loss, were not observed."}
{"id": "PMID:15852", "title": "Long-loop reflexes in the tranquilized monkey.", "content": "EMG responses to sudden displacement of the forelimb were studied in Cebus monkeys tranquilized with Atravet, a phenothiazine tranquilizer. The monkey's forearm was strapped firmly to a manipulandum handle. A torque motor attached at the pivot point of the handle, under servo control, provided reproducible limb displacements. In response to a sudden maintained displacement three periods of EMG activation in biceps muscle occurred with peak latencies of approximately 25, 45 and 85 msec. These correspond to the latencies of the M1, M2 and M3 responses in the alert animal. Similar responses were observed in 'naive' animals which had not previously been used in experimentation. All three responses increased in magnitude with increasing background activity and all appeared to be associated with suppression of EMG activity in the antagonist muscle. M1 and M2 responses were position dependent, M1 being greater in extension than in flexion and M2 the opposite. The position-dependence of the M2 response was produced by a depression of activity following the M1. This depression of activity lasted up to 30 msec following M1 and was directly dependent on the M1 magnitude.", "contents": "Long-loop reflexes in the tranquilized monkey. EMG responses to sudden displacement of the forelimb were studied in Cebus monkeys tranquilized with Atravet, a phenothiazine tranquilizer. The monkey's forearm was strapped firmly to a manipulandum handle. A torque motor attached at the pivot point of the handle, under servo control, provided reproducible limb displacements. In response to a sudden maintained displacement three periods of EMG activation in biceps muscle occurred with peak latencies of approximately 25, 45 and 85 msec. These correspond to the latencies of the M1, M2 and M3 responses in the alert animal. Similar responses were observed in 'naive' animals which had not previously been used in experimentation. All three responses increased in magnitude with increasing background activity and all appeared to be associated with suppression of EMG activity in the antagonist muscle. M1 and M2 responses were position dependent, M1 being greater in extension than in flexion and M2 the opposite. The position-dependence of the M2 response was produced by a depression of activity following the M1. This depression of activity lasted up to 30 msec following M1 and was directly dependent on the M1 magnitude."}
{"id": "PMID:15855", "title": "[Effect of dimedrol, diazoline, diprazin and ethysine on formation of the primary immune response].", "content": "Tests were conducted on mice of the CBA line, immunized through a single intraperitoneal administration of 0.5 ml of a 5% sheep erythrocytes suspension. Antihistaminic agents were introduced by the intraperitoneal route in a dose of 5 mg/kg, first at one time and then repeatedly at various intervals with respect to the initial immunization benadryl and diazoline, when administered in a single dose to mice 24 hours after immunization activated the primary immune response to sheep erythrocytes, whereas phenergan and ethisine manifested merely a tendency toward activation of the immunogenesis. The drugs under study failed to have any significant effect on the titres of serumal hemolysines and hemaglutinines.", "contents": "[Effect of dimedrol, diazoline, diprazin and ethysine on formation of the primary immune response]. Tests were conducted on mice of the CBA line, immunized through a single intraperitoneal administration of 0.5 ml of a 5% sheep erythrocytes suspension. Antihistaminic agents were introduced by the intraperitoneal route in a dose of 5 mg/kg, first at one time and then repeatedly at various intervals with respect to the initial immunization benadryl and diazoline, when administered in a single dose to mice 24 hours after immunization activated the primary immune response to sheep erythrocytes, whereas phenergan and ethisine manifested merely a tendency toward activation of the immunogenesis. The drugs under study failed to have any significant effect on the titres of serumal hemolysines and hemaglutinines."}
{"id": "PMID:15860", "title": "[Effect of cholinergic substances on brain potentials induced by tooth pulp stimulation].", "content": "Introduction of the M-cholinomimetic -- arecoline into the ventricle of the rabbit's brain decreases and of the M-cholinolytic -- atropine -- increases the amplitude of primary responses in the sensomotor region of the cortex, arising out of stimulating the dental pulp. The N-cholinomimetic -- lobeline potentiates the evoked response of the brain cortex, whereas the N-cholinolytic -- beta-ethylene-splasmolytin -- depresses it. It is assumed that the region of the drugs action application are thalamic nuclei.", "contents": "[Effect of cholinergic substances on brain potentials induced by tooth pulp stimulation]. Introduction of the M-cholinomimetic -- arecoline into the ventricle of the rabbit's brain decreases and of the M-cholinolytic -- atropine -- increases the amplitude of primary responses in the sensomotor region of the cortex, arising out of stimulating the dental pulp. The N-cholinomimetic -- lobeline potentiates the evoked response of the brain cortex, whereas the N-cholinolytic -- beta-ethylene-splasmolytin -- depresses it. It is assumed that the region of the drugs action application are thalamic nuclei."}
{"id": "PMID:15861", "title": "[Phencarol--an antihistaminic preparation from the quinuclidylcarbinol group].", "content": "A high antihistaminic activity of quinuclidyl-3-diphenylcarbinol (phencarol) has been ascertained. In pharmacological experiments phencarol is superior to dimedrol (diphenhydramine), both as concerns its antihistaminic activity and the duration of its action. Unlike dimedrol and diprazine (promethazine) it has no inhibitory effect on the central nervous system. With its clinical use phencarol is effective in treating urticaria, Quincke's edema and allergic skin reactions. The drug is well tolerated by the patients and does not produce any inhibitory or soporific action. Phencarol has an authorized permission to be used for medical purposes.", "contents": "[Phencarol--an antihistaminic preparation from the quinuclidylcarbinol group]. A high antihistaminic activity of quinuclidyl-3-diphenylcarbinol (phencarol) has been ascertained. In pharmacological experiments phencarol is superior to dimedrol (diphenhydramine), both as concerns its antihistaminic activity and the duration of its action. Unlike dimedrol and diprazine (promethazine) it has no inhibitory effect on the central nervous system. With its clinical use phencarol is effective in treating urticaria, Quincke's edema and allergic skin reactions. The drug is well tolerated by the patients and does not produce any inhibitory or soporific action. Phencarol has an authorized permission to be used for medical purposes."}
{"id": "PMID:15862", "title": "[Study of the effect of corticosterone on erythrocyte membranes by the spin label method].", "content": "Influence of corticosterone on the hare's erythrocyte ghosts is studied by the spin-label method. There exists a correlation between the maximal variation region in the rotational diffusion \"frequency\" of the spin-labels, covalently linked with the membrane protein, and the hormones concentration range within which the effect of corticosterone on the functions of the erythrocyte membranes manifests itself to the greatest degree (permeability to ions, hemolytic effects, etc).", "contents": "[Study of the effect of corticosterone on erythrocyte membranes by the spin label method]. Influence of corticosterone on the hare's erythrocyte ghosts is studied by the spin-label method. There exists a correlation between the maximal variation region in the rotational diffusion \"frequency\" of the spin-labels, covalently linked with the membrane protein, and the hormones concentration range within which the effect of corticosterone on the functions of the erythrocyte membranes manifests itself to the greatest degree (permeability to ions, hemolytic effects, etc)."}
{"id": "PMID:15858", "title": "[Effect of narcotics on impulse conduction in the afferent pathways of visceral nerves].", "content": "In tests set up on cats immobilized with pyraxolone and anatruxonium the effect of non-inhalation narcotics on the evoked potentials of the cortex and subcortical structures with visceral and also somatic, acoustic and photo-stimulation was studied. With stimuli of different modality sodium ethaminal was found to inhibit evoked potentials of the cerebral hemispheres, diencephalon and midbrain cortex. Hexabarbital sodium suppressed biopotentials in specific, associative and non- specific brain structures in the event of visceral and somatic stimulation. Viadril enhanced the amplitude of potentials in all types of stimulation Urethan inhibited potentials in specific pathways of visceral and somatic nerves as well as in associative and non-specific brain structures following visceral, somatic and acoustic stimulation, with the amplitude of potentials to photostimulation then increasing.", "contents": "[Effect of narcotics on impulse conduction in the afferent pathways of visceral nerves]. In tests set up on cats immobilized with pyraxolone and anatruxonium the effect of non-inhalation narcotics on the evoked potentials of the cortex and subcortical structures with visceral and also somatic, acoustic and photo-stimulation was studied. With stimuli of different modality sodium ethaminal was found to inhibit evoked potentials of the cerebral hemispheres, diencephalon and midbrain cortex. Hexabarbital sodium suppressed biopotentials in specific, associative and non- specific brain structures in the event of visceral and somatic stimulation. Viadril enhanced the amplitude of potentials in all types of stimulation Urethan inhibited potentials in specific pathways of visceral and somatic nerves as well as in associative and non-specific brain structures following visceral, somatic and acoustic stimulation, with the amplitude of potentials to photostimulation then increasing."}
{"id": "PMID:15859", "title": "[Effect of several psychopharmacologic preparations on adaptation to stressful conditions].", "content": "Experiments staged on rats demonstrated that the formation of pathological states caused by stress and accompained by the development of ulcerative lesion of the gastric mucosa are associated with the degree of the catecholamines level drop in the mesencephalon and hypothalamus. The application of seduxen and also of combinations consisting of L-DOPA with seduxen, or with an L-adrenoblocking agent-pyroxan tends to reduce the frequency of developing ulcerative lesions of the stomach. The protective effect produced by the combination of L-DOPA with an L-adrenoblocking agent--pyroxan is barred by an additional administration of an beta-adrenoblocking agent--inderal.", "contents": "[Effect of several psychopharmacologic preparations on adaptation to stressful conditions]. Experiments staged on rats demonstrated that the formation of pathological states caused by stress and accompained by the development of ulcerative lesion of the gastric mucosa are associated with the degree of the catecholamines level drop in the mesencephalon and hypothalamus. The application of seduxen and also of combinations consisting of L-DOPA with seduxen, or with an L-adrenoblocking agent-pyroxan tends to reduce the frequency of developing ulcerative lesions of the stomach. The protective effect produced by the combination of L-DOPA with an L-adrenoblocking agent--pyroxan is barred by an additional administration of an beta-adrenoblocking agent--inderal."}
{"id": "PMID:15873", "title": "The photochemical cycle of bacteriorhodopsin.", "content": "The reaction cycle of bacteriorhodopsin in the purple membrane isolated from Halobacterium halobium has been studied by optical absorption spectroscopy using low-temperature and flash kinetic techniques. After absorption of light, bacteriohodopsin passes through at least five distinct intermediates. The temperature and pH dependence of the absorbance changes suggests that branch points and/or reversible steps exist in this cycle. Flash spectroscopy in the presence of a pH-indicating dye shows that the transient release of a proton accompanies the photoreaction cycle. The proton release occurs from the exterior and the uptake is on the cytoplasmic side of the membrane, as required by the function of bacteriorhodopsin as a light-driven proton pump. Proton translocating steps connecting release and uptake are indicated by deuterium isotope effects on the kinetics of the cycle. The rapid decay of a light-induced linear dichroism shows that a chromophore orientation change occurs during the reaction cycle.", "contents": "The photochemical cycle of bacteriorhodopsin. The reaction cycle of bacteriorhodopsin in the purple membrane isolated from Halobacterium halobium has been studied by optical absorption spectroscopy using low-temperature and flash kinetic techniques. After absorption of light, bacteriohodopsin passes through at least five distinct intermediates. The temperature and pH dependence of the absorbance changes suggests that branch points and/or reversible steps exist in this cycle. Flash spectroscopy in the presence of a pH-indicating dye shows that the transient release of a proton accompanies the photoreaction cycle. The proton release occurs from the exterior and the uptake is on the cytoplasmic side of the membrane, as required by the function of bacteriorhodopsin as a light-driven proton pump. Proton translocating steps connecting release and uptake are indicated by deuterium isotope effects on the kinetics of the cycle. The rapid decay of a light-induced linear dichroism shows that a chromophore orientation change occurs during the reaction cycle."}
{"id": "PMID:15874", "title": "Photochemical and chemical studies on the chromophore of bacteriorhodopsin.", "content": "The chromophore (purple complex) of bacteriorhodopsin is reduced by sodium borohydride upon illumination to RPhv with a three-peaked absorption band at 360 nm. Treatment of this reduction product with ultraviolet light or acid yields a modified product from which retro-retinyllysine can be obtained by alkaline hydrolysis. No reduction of the 412 nm complex was found. Under specific conditions the purple complex equilibrates with a photochemically active 460 nm form that can be reduced by borohydride in the dark. This reduction product RP460 behaves idential to RPHV. Reconstitution of the purple complex from chromophore-free membrane (apomembrane) and retinal occurs via intermediates. The first (lambdamax 400nm) shows a three-peaked absorption band and is reduced to RP400 without a change of the three-peaked absorption (lambdamax 360 nm). The same product is obtained from apomembrane and retinol. Detergents shift the absorption band to 330 nm in all cases. From the experiments described no participation of retro-retinal structures during the photochemical cycle can be concluded but stereospecific interaction of the retinal moiety with the protein resulting in a specific retinal conformation os omdocated by the spectral changes observed.", "contents": "Photochemical and chemical studies on the chromophore of bacteriorhodopsin. The chromophore (purple complex) of bacteriorhodopsin is reduced by sodium borohydride upon illumination to RPhv with a three-peaked absorption band at 360 nm. Treatment of this reduction product with ultraviolet light or acid yields a modified product from which retro-retinyllysine can be obtained by alkaline hydrolysis. No reduction of the 412 nm complex was found. Under specific conditions the purple complex equilibrates with a photochemically active 460 nm form that can be reduced by borohydride in the dark. This reduction product RP460 behaves idential to RPHV. Reconstitution of the purple complex from chromophore-free membrane (apomembrane) and retinal occurs via intermediates. The first (lambdamax 400nm) shows a three-peaked absorption band and is reduced to RP400 without a change of the three-peaked absorption (lambdamax 360 nm). The same product is obtained from apomembrane and retinol. Detergents shift the absorption band to 330 nm in all cases. From the experiments described no participation of retro-retinal structures during the photochemical cycle can be concluded but stereospecific interaction of the retinal moiety with the protein resulting in a specific retinal conformation os omdocated by the spectral changes observed."}
{"id": "PMID:15875", "title": "Proton translocation by ATPase and bacteriorhodopsin.", "content": "Stable membrane proteins and lipids are convenient to study biomembranes. Two stable proton translocating proteins were purified and reconstituted into vesicles capable of proton translocation. One was a thermostable ATPase (TF0-F1) of thermophilic bacterium PS3 and the other was rhodopsin of Halobacterium halobium. TF0-F1 was composed of a proton pump moiety (TF1) and a proton channel moiety (TF0). TF1 was the first membrane ATPase which was crystallized and reconstituted from its five polypeptides. Like TF0 and TF1, the rhodopsin in purple membrane was highly stable against dissociating agents, acids and alkali. Phospholipids of these biomembranes were also stable and contained no unsaturated fatty acyl groups. The molecular species of the phospholipids of PS3 were determined by mass chromatography. Measurements were made of the difference in electrochemical potential of protons (deltamicronH+) across the membrane of the reconstituted vesicles. The deltamicronH+ attained was 312 mV in TF0-F1 vesciles and was 230 mV in the rhodopsin vesicles. To conclude that electron transport components are not necessary for ATP synthesis in energy yielding biomembranes, two experiments were performed: The ATP synthesis was observed i) on acid-base treatment of TF0-F1 vesicles, and ii) on illumination of the rhodopsin-TF0-F1 vesicles.", "contents": "Proton translocation by ATPase and bacteriorhodopsin. Stable membrane proteins and lipids are convenient to study biomembranes. Two stable proton translocating proteins were purified and reconstituted into vesicles capable of proton translocation. One was a thermostable ATPase (TF0-F1) of thermophilic bacterium PS3 and the other was rhodopsin of Halobacterium halobium. TF0-F1 was composed of a proton pump moiety (TF1) and a proton channel moiety (TF0). TF1 was the first membrane ATPase which was crystallized and reconstituted from its five polypeptides. Like TF0 and TF1, the rhodopsin in purple membrane was highly stable against dissociating agents, acids and alkali. Phospholipids of these biomembranes were also stable and contained no unsaturated fatty acyl groups. The molecular species of the phospholipids of PS3 were determined by mass chromatography. Measurements were made of the difference in electrochemical potential of protons (deltamicronH+) across the membrane of the reconstituted vesicles. The deltamicronH+ attained was 312 mV in TF0-F1 vesciles and was 230 mV in the rhodopsin vesicles. To conclude that electron transport components are not necessary for ATP synthesis in energy yielding biomembranes, two experiments were performed: The ATP synthesis was observed i) on acid-base treatment of TF0-F1 vesicles, and ii) on illumination of the rhodopsin-TF0-F1 vesicles."}
{"id": "PMID:15877", "title": "Light-dependent cation gradients and electrical potential in Halobacterium halobium cell envelope vesicles.", "content": "Vesicles can be prepared from Halobacterium halobium cell envelopes, which contain properly oriented bacteriorhodopsin and which extrude H+ during illumination. The pH difference that is generated across the membranes is accompanied by an electrical potential of 90-100 mV (interior negative) and the movements of other cations. Among these is the efflux of Na+, which proceeds against its electrochemical potential. The relationship between the size and direction of the light-induced pH gradient and the rate of depletion of Na+ from the vesicles, as well as other evidence, suggest that the active Na+-extrusion is facilitated by a membrane component that exchanges H+ for Na+ with a stoichiometry greater than 1. The gradients of H+ and Na+ are thus coupled to one another. The Na+-gradient (Na+out greater than Na+in), which arises during illumination, plays a major role in energizing the active transport of amino acids.", "contents": "Light-dependent cation gradients and electrical potential in Halobacterium halobium cell envelope vesicles. Vesicles can be prepared from Halobacterium halobium cell envelopes, which contain properly oriented bacteriorhodopsin and which extrude H+ during illumination. The pH difference that is generated across the membranes is accompanied by an electrical potential of 90-100 mV (interior negative) and the movements of other cations. Among these is the efflux of Na+, which proceeds against its electrochemical potential. The relationship between the size and direction of the light-induced pH gradient and the rate of depletion of Na+ from the vesicles, as well as other evidence, suggest that the active Na+-extrusion is facilitated by a membrane component that exchanges H+ for Na+ with a stoichiometry greater than 1. The gradients of H+ and Na+ are thus coupled to one another. The Na+-gradient (Na+out greater than Na+in), which arises during illumination, plays a major role in energizing the active transport of amino acids."}
{"id": "PMID:15878", "title": "Light-activated amino acid transport in Halobacterium halobium envelope vesicles.", "content": "Vesicles prepared from Halobacterium halobium cell envelopes accumulate amino acids in response to light-induced electrical and chemical gradients. Nineteen of 20 commonly occurring amino acids have been shown to be actively accumulated by these vesicles in response to illumination or in response to an artificially created Na-gradient. Sodium-activated amino acid transport for 18 of these amino acids has been shown to occur in direct response to the protonmotive force generated. Glutamate is transported only in response to a sodium gradient. Michaelis constants for the uptake of these amino acids are close or identical whether the amino acids are accumulated in response to a sodium gradient or a protonmotive force (i.e., electrical gradient). On the basis of shared common carriers the transport systems can be divided into eight classes, each responsible for the transport of one or several amino acids, i.e., arginine, lysine, histidine; asparagine, glutamine; alanine, glycine, threonine, serine; leucine, valine, isoleucine, methionine; phenylalanine, tyrosine, tryptophan; aspartate; glutamate; proline. Available evidence suggests that these carriers are symmetrical in that amino acids can be transported equally well in both directions across the vesicle membranes. A tentative working model to account for these observations is presented.", "contents": "Light-activated amino acid transport in Halobacterium halobium envelope vesicles. Vesicles prepared from Halobacterium halobium cell envelopes accumulate amino acids in response to light-induced electrical and chemical gradients. Nineteen of 20 commonly occurring amino acids have been shown to be actively accumulated by these vesicles in response to illumination or in response to an artificially created Na-gradient. Sodium-activated amino acid transport for 18 of these amino acids has been shown to occur in direct response to the protonmotive force generated. Glutamate is transported only in response to a sodium gradient. Michaelis constants for the uptake of these amino acids are close or identical whether the amino acids are accumulated in response to a sodium gradient or a protonmotive force (i.e., electrical gradient). On the basis of shared common carriers the transport systems can be divided into eight classes, each responsible for the transport of one or several amino acids, i.e., arginine, lysine, histidine; asparagine, glutamine; alanine, glycine, threonine, serine; leucine, valine, isoleucine, methionine; phenylalanine, tyrosine, tryptophan; aspartate; glutamate; proline. Available evidence suggests that these carriers are symmetrical in that amino acids can be transported equally well in both directions across the vesicle membranes. A tentative working model to account for these observations is presented."}
{"id": "PMID:15879", "title": "Light energy conservation processes in Halobacterium halobium cells.", "content": "In Halobacterium halobium, proton pumping driven by light or by respiration generates an electrochemical potential difference across the membrane. Energy storage in this form is only transient. Cellular energy transducers competing with proton leaks stabilize this free energy as high energy phosphate bonds, electrochemical potential of other ions, and chemical potential of amino acids and possibly other chemical species. The pH changes induced by light or by respiration in cell suspensions are complicated by proton flows associated with the functioning of the cellular energy transducers. Dominant is the proton inflow coupled to the synthesis of ATP, which has been kinetically resolved. A proton-per-ATP ratio of about 3 is calculated from simultaneous measurements of photophosphorylation and the proton inflow. This value is compatible with the chemiosmotic coupling hypothesis. The time course of the light-induced changes in membrane potential indicates that light-driven pumping increases a dark preexisting potential of about 130 mV only by a small amount (20-30 mV). The complex kinetic features of the membrane potential changes do not closely follow those of the pH changes, indicating that flows of ions other than protons are involved. A qualitative model consistent with the available data is presented. A salient feature of this model is a sudden relaxation of the protonmotive force by a proton inflow through the ATPase when the preexisting protonmotive force is increased by light or respiration and reaches a critical value. The trigger could be either the proton-motive force, the pH gradient, or possibly the internal pH.", "contents": "Light energy conservation processes in Halobacterium halobium cells. In Halobacterium halobium, proton pumping driven by light or by respiration generates an electrochemical potential difference across the membrane. Energy storage in this form is only transient. Cellular energy transducers competing with proton leaks stabilize this free energy as high energy phosphate bonds, electrochemical potential of other ions, and chemical potential of amino acids and possibly other chemical species. The pH changes induced by light or by respiration in cell suspensions are complicated by proton flows associated with the functioning of the cellular energy transducers. Dominant is the proton inflow coupled to the synthesis of ATP, which has been kinetically resolved. A proton-per-ATP ratio of about 3 is calculated from simultaneous measurements of photophosphorylation and the proton inflow. This value is compatible with the chemiosmotic coupling hypothesis. The time course of the light-induced changes in membrane potential indicates that light-driven pumping increases a dark preexisting potential of about 130 mV only by a small amount (20-30 mV). The complex kinetic features of the membrane potential changes do not closely follow those of the pH changes, indicating that flows of ions other than protons are involved. A qualitative model consistent with the available data is presented. A salient feature of this model is a sudden relaxation of the protonmotive force by a proton inflow through the ATPase when the preexisting protonmotive force is increased by light or respiration and reaches a critical value. The trigger could be either the proton-motive force, the pH gradient, or possibly the internal pH."}
{"id": "PMID:15884", "title": "Genetic counselling and prenatal diagnosis for chromosome anomalies. Use of study of spontaneous abortions.", "content": "Genetic counselling for chromosome abnormalities must take into account the fact that such anomalies may develop as an error in oogenesis or spermatogenesis or may be transmitted from parents. Since many chromosomally abnormal embryos are spontaneously aborted, parents with repeated unfavorable outcomes of pregnancy or difficulty in conceiving should be studied by karyotype. The relationship between chromosomal abnormalities and various environmental or biologic factors are discussed. The outcome of a previous pregnancy may indicate the necessity of subsequent fetal evaluation even with chromosomally normal parents.", "contents": "Genetic counselling and prenatal diagnosis for chromosome anomalies. Use of study of spontaneous abortions. Genetic counselling for chromosome abnormalities must take into account the fact that such anomalies may develop as an error in oogenesis or spermatogenesis or may be transmitted from parents. Since many chromosomally abnormal embryos are spontaneously aborted, parents with repeated unfavorable outcomes of pregnancy or difficulty in conceiving should be studied by karyotype. The relationship between chromosomal abnormalities and various environmental or biologic factors are discussed. The outcome of a previous pregnancy may indicate the necessity of subsequent fetal evaluation even with chromosomally normal parents."}
{"id": "PMID:15885", "title": "Prenatal diagnosis of chromosome abnormalities.", "content": "It is possible to define a group of prospective parents who are at risk of producing offspring with disability due to chromosomal abnormalities. Such individuals should have evaluation of the 15 or 16 week fetus by karyotype of amniotic fluid cells. The techniques and problems of such diagnostic procedures are discussed.", "contents": "Prenatal diagnosis of chromosome abnormalities. It is possible to define a group of prospective parents who are at risk of producing offspring with disability due to chromosomal abnormalities. Such individuals should have evaluation of the 15 or 16 week fetus by karyotype of amniotic fluid cells. The techniques and problems of such diagnostic procedures are discussed."}
{"id": "PMID:15886", "title": "Prenatal diagnosis of inborn errors of metabolism.", "content": "More than 50 inborn errors of metabolism can be diagnosed in the fetus. This is accomplished by evaluation of constituents of the cell free amniotic fluid or of cultured or uncultured amniotic fluid cells. Only those syndromes with specific abnormal contributions to amniotic fluid can be so diagnosed. Currently diagnosable diseases and their assay methods are reviewed. Such assay methods must be able to differentiate the unaffected heterozygote from the affected homozygote.", "contents": "Prenatal diagnosis of inborn errors of metabolism. More than 50 inborn errors of metabolism can be diagnosed in the fetus. This is accomplished by evaluation of constituents of the cell free amniotic fluid or of cultured or uncultured amniotic fluid cells. Only those syndromes with specific abnormal contributions to amniotic fluid can be so diagnosed. Currently diagnosable diseases and their assay methods are reviewed. Such assay methods must be able to differentiate the unaffected heterozygote from the affected homozygote."}
{"id": "PMID:15887", "title": "Diagnostic radiology of fetal abnormalities.", "content": "Fetal abnormalities involving the skeletal system, central nervous system or soft tissue may be diagnosed by radiologic methods, as may fetal death. Occasionally standard X-ray is used, but often invasive techniques are required, and should be limited to those patients with valid indications. X-rays of specific fetal anomalies are presented.", "contents": "Diagnostic radiology of fetal abnormalities. Fetal abnormalities involving the skeletal system, central nervous system or soft tissue may be diagnosed by radiologic methods, as may fetal death. Occasionally standard X-ray is used, but often invasive techniques are required, and should be limited to those patients with valid indications. X-rays of specific fetal anomalies are presented."}
{"id": "PMID:15888", "title": "New and future techniques in prenatal diagnosis.", "content": "Fetal evaluation may be accomplished in the future using techniques experimental at this time. These include direct visualization of the fetus by endoscopy, biopsy of fetal tissues, and indirect techniques accomplished in the laboratory. It is hoped that in the future technology may provide us with means to diagnose the abnormal fetus more accurately and rapidly than currently. Possible methods are discussed.", "contents": "New and future techniques in prenatal diagnosis. Fetal evaluation may be accomplished in the future using techniques experimental at this time. These include direct visualization of the fetus by endoscopy, biopsy of fetal tissues, and indirect techniques accomplished in the laboratory. It is hoped that in the future technology may provide us with means to diagnose the abnormal fetus more accurately and rapidly than currently. Possible methods are discussed."}
{"id": "PMID:15889", "title": "Disappearance of para-amino-hippurate from amniotic fluid.", "content": "Eight pregnant women and three pregnant sheep received 400 mg of para-amino-hippurate (PAH) intraaminotically. Serial samples of amniotic fluid and maternal blood were obtained. In sheep samples of fetal blood were also withdrawn. PAH appeared in maternal plasma in all the cases. In all pregnant women PAH disappeared slowly from amniotic fluid (50% in 4 hours). In one ewe the study was performed as in humans and showed the same pattern of disappearance. In the other two, fetal urine was drained outside the amniotic fluid and PAH disappeared from it at a much faster rate (90% in 4 hours). PAH concentration in fetal urine was 100 times higher than in fetal plasma. Our findings in pregnant women seem to suggest that PAH disappears from the amniotic sac by a diffusion mechanism. On the other hand the results found in sheep also suggest that the fetus may have an active role in PAH concentration in amniotic fluid, eliminating part of the substance into maternal blood across the placenta but returning a major portion to the amniotic fluid with fetal urine.", "contents": "Disappearance of para-amino-hippurate from amniotic fluid. Eight pregnant women and three pregnant sheep received 400 mg of para-amino-hippurate (PAH) intraaminotically. Serial samples of amniotic fluid and maternal blood were obtained. In sheep samples of fetal blood were also withdrawn. PAH appeared in maternal plasma in all the cases. In all pregnant women PAH disappeared slowly from amniotic fluid (50% in 4 hours). In one ewe the study was performed as in humans and showed the same pattern of disappearance. In the other two, fetal urine was drained outside the amniotic fluid and PAH disappeared from it at a much faster rate (90% in 4 hours). PAH concentration in fetal urine was 100 times higher than in fetal plasma. Our findings in pregnant women seem to suggest that PAH disappears from the amniotic sac by a diffusion mechanism. On the other hand the results found in sheep also suggest that the fetus may have an active role in PAH concentration in amniotic fluid, eliminating part of the substance into maternal blood across the placenta but returning a major portion to the amniotic fluid with fetal urine."}
{"id": "PMID:15890", "title": "Antepartum fetal arrythmia. A case report.", "content": "On a number of occasions fetal heart arrythmias have been detected during the course of routine antepartum patient examination. A case is presented to illustrate the difficulty of making a definitive diagnosis of the nature of the arrythmia, and its significance in relation to fetal status. Investigation included stressed and nonstressed FHR monitoring, but a definitive diagnosis could not be made during the antepartum period and the patient could, therefore, not be assured of the essentially benign nature of the arrythmia until shortly after the birth of her child. The electrocardiogram obtained from external fetal electrocardiographic monitoring is not sufficiently refined to aid in the antepartum diagnosis of fetal cardiac arrythmias.", "contents": "Antepartum fetal arrythmia. A case report. On a number of occasions fetal heart arrythmias have been detected during the course of routine antepartum patient examination. A case is presented to illustrate the difficulty of making a definitive diagnosis of the nature of the arrythmia, and its significance in relation to fetal status. Investigation included stressed and nonstressed FHR monitoring, but a definitive diagnosis could not be made during the antepartum period and the patient could, therefore, not be assured of the essentially benign nature of the arrythmia until shortly after the birth of her child. The electrocardiogram obtained from external fetal electrocardiographic monitoring is not sufficiently refined to aid in the antepartum diagnosis of fetal cardiac arrythmias."}
{"id": "PMID:15891", "title": "The estimation of gestational age by amniotic fluid analysis and its relationship to fetal growth retardation.", "content": "The relationship between three amniotic fluid parameters (fat staining cells, anucleate cells and creatinine) and gestational age has been studied in 166 samples from 107 patients of known gestational age. Individually there is an unacceptable degree of inaccuracy. However, when the three parameters are combined in a multilinear regression, an equation for gestational age is produced that is reliable to with  +/-14 days in over 90% of cases. This held true when the equation was applied to 60 samples from 45 patients with uncertain dates and related to the paediatric estimate of gestational age. The accuracy was unaltered by intrauterine growth retardation.", "contents": "The estimation of gestational age by amniotic fluid analysis and its relationship to fetal growth retardation. The relationship between three amniotic fluid parameters (fat staining cells, anucleate cells and creatinine) and gestational age has been studied in 166 samples from 107 patients of known gestational age. Individually there is an unacceptable degree of inaccuracy. However, when the three parameters are combined in a multilinear regression, an equation for gestational age is produced that is reliable to with  +/-14 days in over 90% of cases. This held true when the equation was applied to 60 samples from 45 patients with uncertain dates and related to the paediatric estimate of gestational age. The accuracy was unaltered by intrauterine growth retardation."}
{"id": "PMID:15892", "title": "Repeated extra-amniotic administration of prostaglandin F2alpha for midtrimester abortion.", "content": "Midtrimester abortion was induced in 94 of 100 patients at 16 to 24 weeks' gestation by the extra-amniotic administration of 1170 microng of prostaglandin F2alpha (PGF2alpha) every 10 minutes. The number of prostaglandin doses varied from 16 to 24 depending on the patient's response to the prostaglandin. The median abortion time was 10.0 hours, and 82.0% of the patients aborted within 24 hours. Overall, 68.0% of the patients failed to expel the placenta within one hour of abortion of the fetus. Vomiting and diarrhea occurred among 42.0 and 17.0% of the patients, respectively. Compared with the intra-amniotic administration of a single 50 mg dose of PGF2alpha, the extra-amniotic procedure was associated with similar side effect rates, a higher rate of incomplete abortion, and a significantly shorter abortion time.", "contents": "Repeated extra-amniotic administration of prostaglandin F2alpha for midtrimester abortion. Midtrimester abortion was induced in 94 of 100 patients at 16 to 24 weeks' gestation by the extra-amniotic administration of 1170 microng of prostaglandin F2alpha (PGF2alpha) every 10 minutes. The number of prostaglandin doses varied from 16 to 24 depending on the patient's response to the prostaglandin. The median abortion time was 10.0 hours, and 82.0% of the patients aborted within 24 hours. Overall, 68.0% of the patients failed to expel the placenta within one hour of abortion of the fetus. Vomiting and diarrhea occurred among 42.0 and 17.0% of the patients, respectively. Compared with the intra-amniotic administration of a single 50 mg dose of PGF2alpha, the extra-amniotic procedure was associated with similar side effect rates, a higher rate of incomplete abortion, and a significantly shorter abortion time."}
{"id": "PMID:15893", "title": "Pregnancies in the presence of copper intra-uterine devices. Hysterosalpingographic studies.", "content": "Two copper-bearing intrauterine devices--the Cu-7 and Cu-T-200--were investigated to determine why contraceptive failures occur with these devices. For this investigation, 155 multiparous women were followed up for at least 24 months after IUD insertion (T-Cu-200 in 75 cases and the Cu-7 in 80 cases). Three women using the T-Cu-200 and 5 women using the Cu-7 became pregnant during the first year. Hysterosalpingographic findings are presented for 8 of these cases and for 2 additional cases (one with each device) who became pregnant during the second year of follow-up. These indicate that uterine abnormalities and disproportions between the uterine cavity's shape and size and that of the device are the primary reasons for device displacement and partial fundal coverage leading to contraceptive failures.", "contents": "Pregnancies in the presence of copper intra-uterine devices. Hysterosalpingographic studies. Two copper-bearing intrauterine devices--the Cu-7 and Cu-T-200--were investigated to determine why contraceptive failures occur with these devices. For this investigation, 155 multiparous women were followed up for at least 24 months after IUD insertion (T-Cu-200 in 75 cases and the Cu-7 in 80 cases). Three women using the T-Cu-200 and 5 women using the Cu-7 became pregnant during the first year. Hysterosalpingographic findings are presented for 8 of these cases and for 2 additional cases (one with each device) who became pregnant during the second year of follow-up. These indicate that uterine abnormalities and disproportions between the uterine cavity's shape and size and that of the device are the primary reasons for device displacement and partial fundal coverage leading to contraceptive failures."}
{"id": "PMID:15894", "title": "Estrogen-progesterone withdrawal bleeding in diagnosis of early pregnancy.", "content": "This study was designed to evaluate the efficacy of an exogenous estrogen-progesterone preparation for inducing \"withdrawal bleeding\" in non-pregnant women, a procedure used in some areas for the diagnosis of early pregnancy. Three hundred patients not desiring to be pregnant and with no signs of pregnancy other than menses delayed by 14 days or less were randomly assigned to treatment or control groups. The treatment group received an intramuscular injection of 50 mg progesterone and 3 mg oestradiol benzoate in oil. The control group received no hormonal injection. There was no significant difference between the two groups in the incidence of uterine bleeding within 7 days. Thus, the hormonal preparation was ineffective in inducing \"withdrawal bleeding\". Its use as a diagnostic test for pregnancy is not recommended.", "contents": "Estrogen-progesterone withdrawal bleeding in diagnosis of early pregnancy. This study was designed to evaluate the efficacy of an exogenous estrogen-progesterone preparation for inducing \"withdrawal bleeding\" in non-pregnant women, a procedure used in some areas for the diagnosis of early pregnancy. Three hundred patients not desiring to be pregnant and with no signs of pregnancy other than menses delayed by 14 days or less were randomly assigned to treatment or control groups. The treatment group received an intramuscular injection of 50 mg progesterone and 3 mg oestradiol benzoate in oil. The control group received no hormonal injection. There was no significant difference between the two groups in the incidence of uterine bleeding within 7 days. Thus, the hormonal preparation was ineffective in inducing \"withdrawal bleeding\". Its use as a diagnostic test for pregnancy is not recommended."}
{"id": "PMID:15895", "title": "Carcinoma in situ of the Fallopian tube associated with cervical carcinoma. Case report.", "content": "A case of carcinoma in situ of the fallopian tube in a 55-year-old woman, associated to cervical carcinoma is described. The necessary criteria for the diagnosis of pre-invasive carcinoma of the fallopian tube, among which the number of mitoses seems to be of great importance, are discussed. This previously unreported association of carcinoma in situ of the fallopian tube, with carcinoma of the uterine cervix, emphasizes the notion of the multicentric neoplastic possibilities of the m\u00fcllerian tract derivatives.", "contents": "Carcinoma in situ of the Fallopian tube associated with cervical carcinoma. Case report. A case of carcinoma in situ of the fallopian tube in a 55-year-old woman, associated to cervical carcinoma is described. The necessary criteria for the diagnosis of pre-invasive carcinoma of the fallopian tube, among which the number of mitoses seems to be of great importance, are discussed. This previously unreported association of carcinoma in situ of the fallopian tube, with carcinoma of the uterine cervix, emphasizes the notion of the multicentric neoplastic possibilities of the m\u00fcllerian tract derivatives."}
{"id": "PMID:15896", "title": "A transcutaneous PO2 electrode for continuous monitoring of fetal state during delivery.", "content": "A transcutaneous PO2 electrode has been designed and constructed for the continuous measurement of fetal oxygen tension during labor and delivery. The electrode, tested in vitro, has a low oxygen consumption, a short response time, 10 sec, and a sufficient stability, 5% over 3 hr. The in vivo performance of the electrode, tested in neonates, shows a good correlation between transcutaneous PO2 and PO2 measured in samples of arterial blood. The continous registration of fetal tcPO2 during labor and delivery is exemplified.", "contents": "A transcutaneous PO2 electrode for continuous monitoring of fetal state during delivery. A transcutaneous PO2 electrode has been designed and constructed for the continuous measurement of fetal oxygen tension during labor and delivery. The electrode, tested in vitro, has a low oxygen consumption, a short response time, 10 sec, and a sufficient stability, 5% over 3 hr. The in vivo performance of the electrode, tested in neonates, shows a good correlation between transcutaneous PO2 and PO2 measured in samples of arterial blood. The continous registration of fetal tcPO2 during labor and delivery is exemplified."}
{"id": "PMID:15897", "title": "A new technique and instruments for delivery of the Fallopian tube in female sterilization.", "content": "This report describes an instrument designed for locating and delivering the Fallopian tube through an incision of less than 2 cm. Since no gas insufflation, fibre optic illumination, or electricity is required for successful use of this instrument, it is well suited for performing outpatient tubal sterilizations in areas where other methods, such as laparoscopic procedures, are not feasible.", "contents": "A new technique and instruments for delivery of the Fallopian tube in female sterilization. This report describes an instrument designed for locating and delivering the Fallopian tube through an incision of less than 2 cm. Since no gas insufflation, fibre optic illumination, or electricity is required for successful use of this instrument, it is well suited for performing outpatient tubal sterilizations in areas where other methods, such as laparoscopic procedures, are not feasible."}
{"id": "PMID:15898", "title": "The effect of indomethacin in labour at term.", "content": "The effect of indomethacin as an antagonist to prostaglandin was evaluated on a series of 16 women during spontaneous labour in the ninth month of pregnancy. The evaluation of the effect of indomethacin on the progression of labour was determined by the deviation from the normal curve of Friedman. In 8 cases there was complete cessation of labour from 3 to 192 hours and in 8 additional cases there was protraction of the active phase from 3 to 17 hours. In 2 cases there was no effect. Seven births terminated spontaneously and in 9 cases it was necessary to administer pitocin intravenously to strengthen or renew contractions in order to terminate the pregnancy. There is no correlation between the obstetric state (the degree of cervical dilation, or effacement or rupture of membranes) at the time of indomethacin administration and the uterine response, or the speed of return to the normal curve of Friedman. The effect of indomethacin, as an antagonist to prostaglandin, at the time of labour was studied.", "contents": "The effect of indomethacin in labour at term. The effect of indomethacin as an antagonist to prostaglandin was evaluated on a series of 16 women during spontaneous labour in the ninth month of pregnancy. The evaluation of the effect of indomethacin on the progression of labour was determined by the deviation from the normal curve of Friedman. In 8 cases there was complete cessation of labour from 3 to 192 hours and in 8 additional cases there was protraction of the active phase from 3 to 17 hours. In 2 cases there was no effect. Seven births terminated spontaneously and in 9 cases it was necessary to administer pitocin intravenously to strengthen or renew contractions in order to terminate the pregnancy. There is no correlation between the obstetric state (the degree of cervical dilation, or effacement or rupture of membranes) at the time of indomethacin administration and the uterine response, or the speed of return to the normal curve of Friedman. The effect of indomethacin, as an antagonist to prostaglandin, at the time of labour was studied."}
{"id": "PMID:15899", "title": "Iron deficiency anaemia in Nigerian pregnant women.", "content": "Ninety-four Nigerian pregnant women, many of who had mild to moderate anaemia, were investigated for the presence of iron deficiency. Using the bone marrow as the diagnostic index, 90% of these patients were found to be iron deficient. Iron deficiency is thus common among our expectant mothers. They should, therefore, be given iron supplement in addition to the present practice of folic acid and antimalarials, throughout pregnancy and the puerperium.", "contents": "Iron deficiency anaemia in Nigerian pregnant women. Ninety-four Nigerian pregnant women, many of who had mild to moderate anaemia, were investigated for the presence of iron deficiency. Using the bone marrow as the diagnostic index, 90% of these patients were found to be iron deficient. Iron deficiency is thus common among our expectant mothers. They should, therefore, be given iron supplement in addition to the present practice of folic acid and antimalarials, throughout pregnancy and the puerperium."}
{"id": "PMID:15900", "title": "A suggested set of working definitions and criteria applicable to induction of labour.", "content": "A list of prerequisites, essential items of information and definitions applying to studies on induction of labour is presented. It is suggested that their use would permit proper analysis and comparison of results obtained by different investigators.", "contents": "A suggested set of working definitions and criteria applicable to induction of labour. A list of prerequisites, essential items of information and definitions applying to studies on induction of labour is presented. It is suggested that their use would permit proper analysis and comparison of results obtained by different investigators."}
{"id": "PMID:15901", "title": "Endometrial control: a comparative study of three oral contraceptives.", "content": "Shortly after completing an OC cycle the relative hormonal deficit caused by discontinuing the hormones results in withdrawal bleeding. Similarly, if one or more oral contraceptive tablets are missed during a cycle, the resulting deficiency may cause breakthrough bleeding. A lower incidence of breakthrough bleeding on the day after one oral contraceptive tablet is missed and later onset of withdrawal bleeding indicate that a particular OC provides better endometrial control. These two measurements are used as indices to compare the endometrial control provided by Ovral, Norinyl 1/50, and Nortestrin 1 in a study of 480 women at the Planned Parenthood Clinic in Seattle during 1974 and 1975. An analysis of the data shows that the normal chance of breakthrough bleeding on a particular day when one oral contraceptive tablet is not missed on the previous day is 0.017, 0.022, and 0.022 for Ovral, Norinyl, Norlestrin users, but the chance on the day after a contraceptive tablet is missed increased by 13 to 16 times for each of the three OCs. Ovral provides more sustained endometrial control than Norinyl and Norlestrin, however, as indicated by its lower probability of breakthrough bleeding on the day a contraceptive tablet is missed and by its later onset of withdrawal bleeding.", "contents": "Endometrial control: a comparative study of three oral contraceptives. Shortly after completing an OC cycle the relative hormonal deficit caused by discontinuing the hormones results in withdrawal bleeding. Similarly, if one or more oral contraceptive tablets are missed during a cycle, the resulting deficiency may cause breakthrough bleeding. A lower incidence of breakthrough bleeding on the day after one oral contraceptive tablet is missed and later onset of withdrawal bleeding indicate that a particular OC provides better endometrial control. These two measurements are used as indices to compare the endometrial control provided by Ovral, Norinyl 1/50, and Nortestrin 1 in a study of 480 women at the Planned Parenthood Clinic in Seattle during 1974 and 1975. An analysis of the data shows that the normal chance of breakthrough bleeding on a particular day when one oral contraceptive tablet is not missed on the previous day is 0.017, 0.022, and 0.022 for Ovral, Norinyl, Norlestrin users, but the chance on the day after a contraceptive tablet is missed increased by 13 to 16 times for each of the three OCs. Ovral provides more sustained endometrial control than Norinyl and Norlestrin, however, as indicated by its lower probability of breakthrough bleeding on the day a contraceptive tablet is missed and by its later onset of withdrawal bleeding."}
{"id": "PMID:15902", "title": "Minilaparotomy for female sterilization: a feasibility study of a new technique.", "content": "Female sterilization via a minilaparotomy incision was performed on 30 patients at Al-Azhar University Teaching Hospital in Cairo, Egypt. A uterine sound fed through a Foley catheter was used as a uterine elevator. A 2 cm suprapubic transverse laparotomy was performed and sterilization was accomplished by fimbriectomy. Twenty patients received general anesthesia and 10 patients initially received local anesthesia. Surgical time ranged from 7 to 15 min, and the average duration of hospitalization was 8 hours. Blood loss was small, and no patient was transfused. One patient had a wound infection. This pilot study indicates that this procedure is relatively simple, safe and inexpensive.", "contents": "Minilaparotomy for female sterilization: a feasibility study of a new technique. Female sterilization via a minilaparotomy incision was performed on 30 patients at Al-Azhar University Teaching Hospital in Cairo, Egypt. A uterine sound fed through a Foley catheter was used as a uterine elevator. A 2 cm suprapubic transverse laparotomy was performed and sterilization was accomplished by fimbriectomy. Twenty patients received general anesthesia and 10 patients initially received local anesthesia. Surgical time ranged from 7 to 15 min, and the average duration of hospitalization was 8 hours. Blood loss was small, and no patient was transfused. One patient had a wound infection. This pilot study indicates that this procedure is relatively simple, safe and inexpensive."}
{"id": "PMID:15903", "title": "Midtrimester abortion: a comparison of intraamniotic prostaglandin F2alpha and hypertonic saline.", "content": "The safety and effectiveness of two intraamniotic prostaglandin F2alpha (PGF2alpha) dose schedules (a single 50 mg dose and a repeated 25 mg dose) and intraamniotic hypertonic saline were evaluated in a study where each abortion procedure was randomly assigned to 50 patients. All patients were at 16 to 20 weeks' gestation. Rates of gastrointestinal and other side effects were generally higher for the 50 mg PGF2alpha dose schedule than for the other two procedures. The repeated 25 mg PGF2alpha dose schedule resulted in higher 24-hour (68.0%) and 48-hour (98.0%) cumulative abortion rates than the 50 mg PGF2alpha dose schedule (54.0%, 92.0%) or saline (34.7%, 91.8%). Rates of spontaneous placental expulsion were highest for the repeated 25 mg PGF2alpha dose (74.0%) and lowest for the 50 mg PGF2alpha dose schedule (40.0%).", "contents": "Midtrimester abortion: a comparison of intraamniotic prostaglandin F2alpha and hypertonic saline. The safety and effectiveness of two intraamniotic prostaglandin F2alpha (PGF2alpha) dose schedules (a single 50 mg dose and a repeated 25 mg dose) and intraamniotic hypertonic saline were evaluated in a study where each abortion procedure was randomly assigned to 50 patients. All patients were at 16 to 20 weeks' gestation. Rates of gastrointestinal and other side effects were generally higher for the 50 mg PGF2alpha dose schedule than for the other two procedures. The repeated 25 mg PGF2alpha dose schedule resulted in higher 24-hour (68.0%) and 48-hour (98.0%) cumulative abortion rates than the 50 mg PGF2alpha dose schedule (54.0%, 92.0%) or saline (34.7%, 91.8%). Rates of spontaneous placental expulsion were highest for the repeated 25 mg PGF2alpha dose (74.0%) and lowest for the 50 mg PGF2alpha dose schedule (40.0%)."}
{"id": "PMID:15904", "title": "An assessment of the side effects of switching from one oral contraceptive to another.", "content": "Side effects associated with three oral contraceptives were evaluated in a study in which women were switched to Norlestrin 1 from either Ovral (64 subjects) or Norinyl 1/50 (26 subjects). In the cycle prior to crossover, breast discomfort was more frequent among Norinyl users than among Ovral users. The prevalence of all other reported side effects was not significantly different for Norinyl and Ovral. The crossover to Norlestrin did not significantly change the numbers of patients reporting side effects. By the end of third Norlestrin cycle, rates of all side effects were similar for women who were switched from either Ovral or Norinyl.", "contents": "An assessment of the side effects of switching from one oral contraceptive to another. Side effects associated with three oral contraceptives were evaluated in a study in which women were switched to Norlestrin 1 from either Ovral (64 subjects) or Norinyl 1/50 (26 subjects). In the cycle prior to crossover, breast discomfort was more frequent among Norinyl users than among Ovral users. The prevalence of all other reported side effects was not significantly different for Norinyl and Ovral. The crossover to Norlestrin did not significantly change the numbers of patients reporting side effects. By the end of third Norlestrin cycle, rates of all side effects were similar for women who were switched from either Ovral or Norinyl."}
{"id": "PMID:15905", "title": "Practicability of ultrasonography for assessing fetal age and weight in early pregnancy.", "content": "This study was conducted to evaluate (1) the feasibility and accuracy of the B-Scan technique for measuring biparietal diameter (BPD) in utero, (2) the accuracy of the B-Scan technique for predicting fetal age and weight, and (3) parameters of fetal growth in pregnancies of less than 21 weeks's gestation. Forty-one subjects underwent diagnostic ultrasonography before induction of therapeutic abortion with Prostaglandin F2alpha. Following abortion, fetal crown-to-rump length (CRL), crown-to-heel (CHL), BPD, and fetal weight were measured directly. After 13 menstrual weeks' gestation the BPD could be accurately measured by ultrasound. The relationship of BPD to gestational age and fetal weight and the indices of fetal growth as measured by the CRL and CHL were established. It is concluded that ultrasound is a useful adjuvant to clinical assessment of fetal age and weight in patients form 13 to 21 menstrual weeks' gestation.", "contents": "Practicability of ultrasonography for assessing fetal age and weight in early pregnancy. This study was conducted to evaluate (1) the feasibility and accuracy of the B-Scan technique for measuring biparietal diameter (BPD) in utero, (2) the accuracy of the B-Scan technique for predicting fetal age and weight, and (3) parameters of fetal growth in pregnancies of less than 21 weeks's gestation. Forty-one subjects underwent diagnostic ultrasonography before induction of therapeutic abortion with Prostaglandin F2alpha. Following abortion, fetal crown-to-rump length (CRL), crown-to-heel (CHL), BPD, and fetal weight were measured directly. After 13 menstrual weeks' gestation the BPD could be accurately measured by ultrasound. The relationship of BPD to gestational age and fetal weight and the indices of fetal growth as measured by the CRL and CHL were established. It is concluded that ultrasound is a useful adjuvant to clinical assessment of fetal age and weight in patients form 13 to 21 menstrual weeks' gestation."}
{"id": "PMID:15906", "title": "Laparoscopic sterilization in the puerperium: a review of international experience.", "content": "The feasibility of using laparoscopic techinques for pueperal sterilization has been demonstrated on three continents. While the operation is not suggested to replace all other methods of pueperal sterilization, it is advantageous in selected situations.", "contents": "Laparoscopic sterilization in the puerperium: a review of international experience. The feasibility of using laparoscopic techinques for pueperal sterilization has been demonstrated on three continents. While the operation is not suggested to replace all other methods of pueperal sterilization, it is advantageous in selected situations."}
{"id": "PMID:15907", "title": "A comparative study of electrocoagulation and tubal rings for tubal occlusion at laparoscopy.", "content": "The surgical and early postoperative complications and complaints associated with laparoscopic sterilization using electrocoagulation or tubal rings for tubal occlusion were evaluated in a comparative study. Procedures were randomly assigned to subjects (electrocoagulation to 151 subjects and tubal rings to 148 subjects). Difficulties in carrying out the sterillization procedures occurred more frequently when tubal rings were used (6.1%) than when electrocoagulation was used (2.0%). Rates of complications occurring at the time of surgery were similar for the two procedures. However, one patient in the electrocoagulation group had a bowel burn. Postoperative pelvic and abdominal pain were reported by a significantly higher proportion of the tubal ring cases (32.0%) than electrocoagulation cases (19.4%). It appears that although the incidence of surgical difficulties and pain may be somewhat more frequent with the tubal ring, the avoidance of such potentially serious complications as bowel burns may make femal sterilization by the tubal ring method preferable.", "contents": "A comparative study of electrocoagulation and tubal rings for tubal occlusion at laparoscopy. The surgical and early postoperative complications and complaints associated with laparoscopic sterilization using electrocoagulation or tubal rings for tubal occlusion were evaluated in a comparative study. Procedures were randomly assigned to subjects (electrocoagulation to 151 subjects and tubal rings to 148 subjects). Difficulties in carrying out the sterillization procedures occurred more frequently when tubal rings were used (6.1%) than when electrocoagulation was used (2.0%). Rates of complications occurring at the time of surgery were similar for the two procedures. However, one patient in the electrocoagulation group had a bowel burn. Postoperative pelvic and abdominal pain were reported by a significantly higher proportion of the tubal ring cases (32.0%) than electrocoagulation cases (19.4%). It appears that although the incidence of surgical difficulties and pain may be somewhat more frequent with the tubal ring, the avoidance of such potentially serious complications as bowel burns may make femal sterilization by the tubal ring method preferable."}
{"id": "PMID:15908", "title": "Prophylactic antibiotic in elective gynaecological and obstetrical major surgery.", "content": "A prospective controlled study of 580 patients who underwent non-radical major gynaecological or obstetrical surgery examined the use of prophylactic antibiotics. The test group of patients (290) showed a significantly lower (P=0.01) incidence of the total complications and the non-infective complication rate as against those among controls (290). The duration of hospitalisation was significantly reduced for both vaginal and abdominal surgery in the test group of patients as against those in the controls. There was no evidence of increased incidence of bacterial resistance or superinfection. The authors recommend the use of prophylactic antibiotic on a short term basis (for a total duration of 4 days), commencing preoperatively to achieve a significant reduction in the infective postoperative morbidity and a shorter stay by the patients.", "contents": "Prophylactic antibiotic in elective gynaecological and obstetrical major surgery. A prospective controlled study of 580 patients who underwent non-radical major gynaecological or obstetrical surgery examined the use of prophylactic antibiotics. The test group of patients (290) showed a significantly lower (P=0.01) incidence of the total complications and the non-infective complication rate as against those among controls (290). The duration of hospitalisation was significantly reduced for both vaginal and abdominal surgery in the test group of patients as against those in the controls. There was no evidence of increased incidence of bacterial resistance or superinfection. The authors recommend the use of prophylactic antibiotic on a short term basis (for a total duration of 4 days), commencing preoperatively to achieve a significant reduction in the infective postoperative morbidity and a shorter stay by the patients."}
{"id": "PMID:15909", "title": "Ossification centers as evidence of fetal lung maturity.", "content": "Fetal pulmonary maturity based on visualization of one or both fetal knee secondary centers of ossification was assessed in 84 gravidas. Amniotic fluid lecithin/sphingomyelin ration of 2:1 or greater was the criterion of fetal lung maturity. It was concluded that when antenatal radiographs reveal the presence of both centers of ossification, fetal lung maturity can be assured in 100% of the fetuses. When the distal femoral center along is seen, only 60% of the fetuses will have mature lungs.", "contents": "Ossification centers as evidence of fetal lung maturity. Fetal pulmonary maturity based on visualization of one or both fetal knee secondary centers of ossification was assessed in 84 gravidas. Amniotic fluid lecithin/sphingomyelin ration of 2:1 or greater was the criterion of fetal lung maturity. It was concluded that when antenatal radiographs reveal the presence of both centers of ossification, fetal lung maturity can be assured in 100% of the fetuses. When the distal femoral center along is seen, only 60% of the fetuses will have mature lungs."}
{"id": "PMID:15910", "title": "A comparative study of hysterosalpingography and laparoscopy in the investigation of infertility.", "content": "A comparison of hysterosalpingography and laparoscopy was carried out on 79 infertile women. Out of these, 60 had abnormal and 19 had normal hysterosalpingograms. Of the 19 patients with normal X-rays, nine (47%) had abnormal findings during laparoscopy. In 62% of patients with abnormal hysterosalpingograms, laparoscopic findings confirmed the radiological diagnosis, however in 38% the findings differed. Though hysterosalpingography is an important part of infertility evaluation, a final and definite diagnosis requires endoscopic evaluation of the pelvis.", "contents": "A comparative study of hysterosalpingography and laparoscopy in the investigation of infertility. A comparison of hysterosalpingography and laparoscopy was carried out on 79 infertile women. Out of these, 60 had abnormal and 19 had normal hysterosalpingograms. Of the 19 patients with normal X-rays, nine (47%) had abnormal findings during laparoscopy. In 62% of patients with abnormal hysterosalpingograms, laparoscopic findings confirmed the radiological diagnosis, however in 38% the findings differed. Though hysterosalpingography is an important part of infertility evaluation, a final and definite diagnosis requires endoscopic evaluation of the pelvis."}
{"id": "PMID:15911", "title": "Morphologic studies on the non-cancerous cervix in Jamaicans at different ages.", "content": "A morphologic investigation on 100 cervices removed at autopsy from negro Jamaican women at different ages showed that columnar epithelium was frequently located on the portio vaginalis at all ages. The absence of this phenomenon in some fetal cervices supports the hypothesis of embryologic displacement rather than stimulation by maternal estrogens. Squamous metaplasia was common at all ages, even in the fetus; it showed little relationship to chronic inflammation, but the high frequency in post-pubertal cases (80%) could have some relationship to the high incidence of cervical cancer in Jamaica. Chronic inflammation was not observed in the fetal cervix but occurred in most infants in whom it was attributed to congenital \"erosion\". However, the cervices of children revealed a marked discrepancy between the presence of \"erosion\" and the degree and frequency of chronic inflammation (83%). This change is unexplained and requires further study.", "contents": "Morphologic studies on the non-cancerous cervix in Jamaicans at different ages. A morphologic investigation on 100 cervices removed at autopsy from negro Jamaican women at different ages showed that columnar epithelium was frequently located on the portio vaginalis at all ages. The absence of this phenomenon in some fetal cervices supports the hypothesis of embryologic displacement rather than stimulation by maternal estrogens. Squamous metaplasia was common at all ages, even in the fetus; it showed little relationship to chronic inflammation, but the high frequency in post-pubertal cases (80%) could have some relationship to the high incidence of cervical cancer in Jamaica. Chronic inflammation was not observed in the fetal cervix but occurred in most infants in whom it was attributed to congenital \"erosion\". However, the cervices of children revealed a marked discrepancy between the presence of \"erosion\" and the degree and frequency of chronic inflammation (83%). This change is unexplained and requires further study."}
{"id": "PMID:15912", "title": "A technique for the induction of labor by the extraovular administration of prostaglandin F2alpha.", "content": "Prostaglandin F2alpha (PG F2alpha) was administered to pregnant women at a dosage of 50 microng or 100 microng by extraovular route around the expected time of childbirth in order to induce labor. (1) PG F2alpha 50 microng or 100 microng dissolved in 10 ml of physiological saline solution was infused by extraovular administration through the cervical canal of the uterus with the use of Nelaton catheter No. 9. The catheter was then immediately withdrawn and the patient allowed to return home. (2) Instilation of 10ml of physiological saline solution was carried out for control purposes. (3) Those who reported labor contractions within 24 hours after the infusion were regarded as cases of excellent response, and those who reported labor contractions more than 24 hours after the infusion, or those who showed dilatation and improvement in effacement of the uterine cervical canal though without the occurrence of labor contractions were deemed to be cases of good response. The overall positive response rate (excellent plus good) was 78.9% for primiparae and 85.7% for multiparae in the group receiving 50 microng and 89.5% for primiparae and 100% for multiparae in the group receiving 100 microng. (4) Labor contraction were induced at a rate of almost 100% in those who showed dilatation of the cervical canal of the uterus to the extent of 3 cm or more and effacement to the extent of 50% or more. (5) It is advisable to perform reinfusion of PG F2alpha or instilation of PG F2alpha as a post-treatment in patients with good responses. (6) The infusion of PG F2alpha is effective for the induction of labor in older primiparae, cases of breech presentation and suspected cases of CPD. (7) There were some cases of enhanced response when PG F2alpha was given as posttreatment.", "contents": "A technique for the induction of labor by the extraovular administration of prostaglandin F2alpha. Prostaglandin F2alpha (PG F2alpha) was administered to pregnant women at a dosage of 50 microng or 100 microng by extraovular route around the expected time of childbirth in order to induce labor. (1) PG F2alpha 50 microng or 100 microng dissolved in 10 ml of physiological saline solution was infused by extraovular administration through the cervical canal of the uterus with the use of Nelaton catheter No. 9. The catheter was then immediately withdrawn and the patient allowed to return home. (2) Instilation of 10ml of physiological saline solution was carried out for control purposes. (3) Those who reported labor contractions within 24 hours after the infusion were regarded as cases of excellent response, and those who reported labor contractions more than 24 hours after the infusion, or those who showed dilatation and improvement in effacement of the uterine cervical canal though without the occurrence of labor contractions were deemed to be cases of good response. The overall positive response rate (excellent plus good) was 78.9% for primiparae and 85.7% for multiparae in the group receiving 50 microng and 89.5% for primiparae and 100% for multiparae in the group receiving 100 microng. (4) Labor contraction were induced at a rate of almost 100% in those who showed dilatation of the cervical canal of the uterus to the extent of 3 cm or more and effacement to the extent of 50% or more. (5) It is advisable to perform reinfusion of PG F2alpha or instilation of PG F2alpha as a post-treatment in patients with good responses. (6) The infusion of PG F2alpha is effective for the induction of labor in older primiparae, cases of breech presentation and suspected cases of CPD. (7) There were some cases of enhanced response when PG F2alpha was given as posttreatment."}
{"id": "PMID:15913", "title": "Plasma estradiol-17 beta as an index of fetoplacental function.", "content": "Serial plasma unconjugated estradiol-17 beta was measured by a radioimmunoassay method in 26 cases of hypertensive disorder of pregnancy, 13 cases of poor obstetric history and 4 cases of intra-uterine growth retardation. There was considerable overlap of hormonal values between pregnancies, resulting in delivery of normal fetuses and those with dysmature fetuses. Serial estimation of estradiol-17 beta were not found to be useful in the prediction of intra-uterine death, although low values were obtained after fetal death has occurred. Estradiol-17 beta estimation appeared to be an unreliable index of fetoplacental function.", "contents": "Plasma estradiol-17 beta as an index of fetoplacental function. Serial plasma unconjugated estradiol-17 beta was measured by a radioimmunoassay method in 26 cases of hypertensive disorder of pregnancy, 13 cases of poor obstetric history and 4 cases of intra-uterine growth retardation. There was considerable overlap of hormonal values between pregnancies, resulting in delivery of normal fetuses and those with dysmature fetuses. Serial estimation of estradiol-17 beta were not found to be useful in the prediction of intra-uterine death, although low values were obtained after fetal death has occurred. Estradiol-17 beta estimation appeared to be an unreliable index of fetoplacental function."}
{"id": "PMID:15914", "title": "Studies on maternal mortality in Mexico.", "content": "The sociocultural, psychological, and medical effects of maternal death are described and analyzed for the purpose of appraising the value of the given death as a measure of the quality of medical care. The work of the Maternal Mortality Committee of the Hospital de Gineco-Obstetetricia No. 1 of the Mexican Social Security Institute over its three years of operation and some results on responsiblity for death and its possible predictabilty are presented. The results show that it is necessary to broaden the Committee's functions in a social, professional, and institutional context so that the indicated factors may be objectively assessed and also that the Committee be transformed into a dynamic organism that will contribute to solving the problem. Recommendations for the operation of the Maternal Mortality Committees are given.", "contents": "Studies on maternal mortality in Mexico. The sociocultural, psychological, and medical effects of maternal death are described and analyzed for the purpose of appraising the value of the given death as a measure of the quality of medical care. The work of the Maternal Mortality Committee of the Hospital de Gineco-Obstetetricia No. 1 of the Mexican Social Security Institute over its three years of operation and some results on responsiblity for death and its possible predictabilty are presented. The results show that it is necessary to broaden the Committee's functions in a social, professional, and institutional context so that the indicated factors may be objectively assessed and also that the Committee be transformed into a dynamic organism that will contribute to solving the problem. Recommendations for the operation of the Maternal Mortality Committees are given."}
{"id": "PMID:15915", "title": "Response of fetal acid--base balance to duration of second stage of labour.", "content": "Data from 4081 vaginal deliveries (no caesarean sections) were analyzed retrospectively (IBM 730/158) with regard to duration of second and \"final stage\" of labour and fetal outcome (acid-base balance and apgar scores). The average duration of the two periods amounted to 22.8+/-29.6 and 9.9+/-7.8 min. Mean pH (UA) was 7.268+/-0.084 and the acidotic risk (pH less than 7.20, pH less than 7.10) 13.4 and 1.6% respectively. The distribution of the Apgar-scores after 1 min was assessed: 0-3: 1.7%, 4-6: 5.4%, 7-10: 92.9%. The dependance of the time variables from parity was studied. Two samples (N1=1755, N2=1098) of uncomplicated term pregnancies were chosen according to 7 clinical selection criteria differing only in the presence of cord entanglements at birth. The association between the two time variables and parameters of the fetal acid-base balance in cord blood was evaluated using rank correlation- and polynomial regression analysis. Highly significant correlations (tau) were found between the variable time and actual pH in blood of the umbilical artery and vein as well as pCO2, BEECF and HbO2 in the umbilical vein. The association however is not very close and thus clinically not of great importance. The deltapH (UA & UV) pro 60 min of second (and \"final\") stage of labour was computed and amounted to -0.024 (-0.087) in blood of the umbilical artery and -0.036 (-0.115) in blood of the umbilical vein and -0.017 (-0.062) (UA) and -0.032 (-0.120) units (UV) in the sample with and without apparent cord entanglements at birth respectively. The response of fetal acid-base balance to cord compression during second stage of labour was assesses: The acidotic risk (pH less 7.2) was doubled: 14.5% (7.7%) and AV-differences of all variables were \"opened\" if cordcoilings were observed. Apgar scores were not significantly different. Moreover, the association between AV-differences of each parameter and the variable time was studied: it became evident that with passage of time AV-difference is \"closed\" (-0.052 AV DpH/60 min \"final stage\" of labour, N=1098) indicating time related impairment of placental function. From these observations and data of the literature the conclusion is drawn that second stage of labour should not exceed 45 min in any patient. Furthermore it is concluded that in cases without signs of impending fetal distress it seems to be possible to wait more than 20 (Multipara) or 30 min (Primipara) duration of \"final stage\" without increased risk of fetal peril measured in terms of acidemia and clinical depression. This is valid only in term pregnancies with the possibility of continuous monitoring of FHR, in cases with normal uterine activity, uneventful course of first stage of labour and cooperative, vigorous patients. The indications for termination of delivery by vaginal operations in cases without impending fetal distress are discussed.", "contents": "Response of fetal acid--base balance to duration of second stage of labour. Data from 4081 vaginal deliveries (no caesarean sections) were analyzed retrospectively (IBM 730/158) with regard to duration of second and \"final stage\" of labour and fetal outcome (acid-base balance and apgar scores). The average duration of the two periods amounted to 22.8+/-29.6 and 9.9+/-7.8 min. Mean pH (UA) was 7.268+/-0.084 and the acidotic risk (pH less than 7.20, pH less than 7.10) 13.4 and 1.6% respectively. The distribution of the Apgar-scores after 1 min was assessed: 0-3: 1.7%, 4-6: 5.4%, 7-10: 92.9%. The dependance of the time variables from parity was studied. Two samples (N1=1755, N2=1098) of uncomplicated term pregnancies were chosen according to 7 clinical selection criteria differing only in the presence of cord entanglements at birth. The association between the two time variables and parameters of the fetal acid-base balance in cord blood was evaluated using rank correlation- and polynomial regression analysis. Highly significant correlations (tau) were found between the variable time and actual pH in blood of the umbilical artery and vein as well as pCO2, BEECF and HbO2 in the umbilical vein. The association however is not very close and thus clinically not of great importance. The deltapH (UA & UV) pro 60 min of second (and \"final\") stage of labour was computed and amounted to -0.024 (-0.087) in blood of the umbilical artery and -0.036 (-0.115) in blood of the umbilical vein and -0.017 (-0.062) (UA) and -0.032 (-0.120) units (UV) in the sample with and without apparent cord entanglements at birth respectively. The response of fetal acid-base balance to cord compression during second stage of labour was assesses: The acidotic risk (pH less 7.2) was doubled: 14.5% (7.7%) and AV-differences of all variables were \"opened\" if cordcoilings were observed. Apgar scores were not significantly different. Moreover, the association between AV-differences of each parameter and the variable time was studied: it became evident that with passage of time AV-difference is \"closed\" (-0.052 AV DpH/60 min \"final stage\" of labour, N=1098) indicating time related impairment of placental function. From these observations and data of the literature the conclusion is drawn that second stage of labour should not exceed 45 min in any patient. Furthermore it is concluded that in cases without signs of impending fetal distress it seems to be possible to wait more than 20 (Multipara) or 30 min (Primipara) duration of \"final stage\" without increased risk of fetal peril measured in terms of acidemia and clinical depression. This is valid only in term pregnancies with the possibility of continuous monitoring of FHR, in cases with normal uterine activity, uneventful course of first stage of labour and cooperative, vigorous patients. The indications for termination of delivery by vaginal operations in cases without impending fetal distress are discussed."}
{"id": "PMID:15916", "title": "Ectopic pregnancy in southern Iran: a statistical review of 96 cases.", "content": "A review is presented of 96 cases of ectopic pregnacy over a 7-year period. It is noted that in recent years the incidence of this problem has increased. Inadequately diagnosed and treated pelvic inflammatory disease has been found to be the main predisposing factor (40%). The rate of extra-uterine gestation was 1:336 deliveries. In this study, previous fertility was high, and primigravidae constituted only 10.4% of the total. The effect of previous pelvic operations and pelvic infection is discussed; a statistical review of signs and symptoms is tabulated, and the management of the patient and of concomitant problems is presented.", "contents": "Ectopic pregnancy in southern Iran: a statistical review of 96 cases. A review is presented of 96 cases of ectopic pregnacy over a 7-year period. It is noted that in recent years the incidence of this problem has increased. Inadequately diagnosed and treated pelvic inflammatory disease has been found to be the main predisposing factor (40%). The rate of extra-uterine gestation was 1:336 deliveries. In this study, previous fertility was high, and primigravidae constituted only 10.4% of the total. The effect of previous pelvic operations and pelvic infection is discussed; a statistical review of signs and symptoms is tabulated, and the management of the patient and of concomitant problems is presented."}
{"id": "PMID:15917", "title": "Pyometra.", "content": "Thirteen cases of pyometra without preoperative diagnosis in which vaginal or abdominal surgery was performed, are analysed in the present paper. The histologic examination revealed endocervicitis in all cases, while positive cultures for bacteria were found preoperatively in only eight of the above cases, thus, pyometra was considered to be a symptom of obstruction of the cervical canal.", "contents": "Pyometra. Thirteen cases of pyometra without preoperative diagnosis in which vaginal or abdominal surgery was performed, are analysed in the present paper. The histologic examination revealed endocervicitis in all cases, while positive cultures for bacteria were found preoperatively in only eight of the above cases, thus, pyometra was considered to be a symptom of obstruction of the cervical canal."}
{"id": "PMID:15918", "title": "2,3-diphosphoglycerate, nucleotide phosophate, and organic and inorganic phosphate levels during the early phases of diabetic ketoacidosis.", "content": "The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA). A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P less than 0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment. In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reemphasizes the need for phosphate replacement during the early phases of treatment of DKA.", "contents": "2,3-diphosphoglycerate, nucleotide phosophate, and organic and inorganic phosphate levels during the early phases of diabetic ketoacidosis. The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA). A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P less than 0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment. In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reemphasizes the need for phosphate replacement during the early phases of treatment of DKA."}
{"id": "PMID:15920", "title": "Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals.", "content": "Several anticancer chemicals containing a quinone group were found to stimulate the aerobic oxidation of NADPH by liver microsomes. The enzyme responsible for the above reaction was identified as NADPH-cytochrome c reductase (EC 1.6.2.4), one of the microsomal flavoproteins. The fact that a catalytic amount (20 micronM) of these anticancer chemicals was sufficient to oxidize all the NADPH (100 micronM) indicates that they function as electron carries from the flavoprotein to molecular oxygen. As a corollary, Mitomycin-C and Carbazilquinone stimulated oxygen uptake by Ehrlich ascites tumor cells in the presence of glucose that Daunomycin and Adriamycin failed to do so, although the reason for it remains to be elucidated. Carbazilquinone, in contrast to others, also stimulated the microsomal NADH oxidation.", "contents": "Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals. Several anticancer chemicals containing a quinone group were found to stimulate the aerobic oxidation of NADPH by liver microsomes. The enzyme responsible for the above reaction was identified as NADPH-cytochrome c reductase (EC 1.6.2.4), one of the microsomal flavoproteins. The fact that a catalytic amount (20 micronM) of these anticancer chemicals was sufficient to oxidize all the NADPH (100 micronM) indicates that they function as electron carries from the flavoprotein to molecular oxygen. As a corollary, Mitomycin-C and Carbazilquinone stimulated oxygen uptake by Ehrlich ascites tumor cells in the presence of glucose that Daunomycin and Adriamycin failed to do so, although the reason for it remains to be elucidated. Carbazilquinone, in contrast to others, also stimulated the microsomal NADH oxidation."}
{"id": "PMID:15921", "title": "Late persistence of serum gamma-glutamyl transpeptidase activity after mononucleosis. Report of 3 cases.", "content": "gamma-Glutamyl transpeptidase (GGTP) is a sensitive but nonspecific index hepatobiliary disease. In infectious mononucleosis (IM) or the mononucleosis-like disease attributable to cytomegalovirus (cytomegalovirus-induced IM), GGTP reverted to normal later than aspartate aminotransferase and alkaline phosphatase. In three cases elevated serum GGTP activity persisted for up to 24 months -- raising the question of persistent 'post-IM' hepatitis. Such prolonged GGTP activity was unusual in other late IM specimens. Possible, but unlikely, causes for such persistent GGTP activity are an unusual degree of hepatic damage during acute IM, excessive induction of microsomal enzyme system activity by drugs, or unusual Epstein-Barr virus carrier state activation that might contribute to ongoing hepatic structural damage. Other markers of chronic hepatocellular disease including aspartate aminotrasferase, alkaline phosphatase, and bilirubin were normal in late specimens from these 3 patients. The cause of their persistent elevated GGTP activities remains unknown.", "contents": "Late persistence of serum gamma-glutamyl transpeptidase activity after mononucleosis. Report of 3 cases. gamma-Glutamyl transpeptidase (GGTP) is a sensitive but nonspecific index hepatobiliary disease. In infectious mononucleosis (IM) or the mononucleosis-like disease attributable to cytomegalovirus (cytomegalovirus-induced IM), GGTP reverted to normal later than aspartate aminotransferase and alkaline phosphatase. In three cases elevated serum GGTP activity persisted for up to 24 months -- raising the question of persistent 'post-IM' hepatitis. Such prolonged GGTP activity was unusual in other late IM specimens. Possible, but unlikely, causes for such persistent GGTP activity are an unusual degree of hepatic damage during acute IM, excessive induction of microsomal enzyme system activity by drugs, or unusual Epstein-Barr virus carrier state activation that might contribute to ongoing hepatic structural damage. Other markers of chronic hepatocellular disease including aspartate aminotrasferase, alkaline phosphatase, and bilirubin were normal in late specimens from these 3 patients. The cause of their persistent elevated GGTP activities remains unknown."}
{"id": "PMID:15922", "title": "Medical management of Crohn's disease in adolescence.", "content": "The therapy of Crohn's disease in adolescence must balance the natural disease history of growth suppression, debilitation, and progression against possible drug-related adverse effects on growth and development. In contrast to published guidelines which usually suggest episodic and symptomatic treatment of relapses, we have attempted to suppress disease activity throughout adolescence. Sixteen consecutive adolescent patients treated with continuous medical therapy for a mean duration of 3.5 years are presented. Fourteen received long term prednisone therapy for maintenance of disease suppression. All 16 have been asymptomatic or have had only mild symptoms which did not interfere with regular activities. Only 1 subject had to be rehospitalized. He subsequently underwent bowel surgery. Aternate day corticosteroid administration has been attained in 11 patients; 10 are growing and developing at a normal rate. In total, 13 of 16 have achieved pubertal development appropriate for age. The 8 patients with distal ileal disease have had a consistently excellent response to medical therapy. There have been no major adverse effects from drug therapy. It is concluded that an effort to suppress disease activity continuously in adolsecents with Crohn's disease is warranted. Excellent symptomatic control and normal rate of growth can be expected in patients with primarily ileal disease.", "contents": "Medical management of Crohn's disease in adolescence. The therapy of Crohn's disease in adolescence must balance the natural disease history of growth suppression, debilitation, and progression against possible drug-related adverse effects on growth and development. In contrast to published guidelines which usually suggest episodic and symptomatic treatment of relapses, we have attempted to suppress disease activity throughout adolescence. Sixteen consecutive adolescent patients treated with continuous medical therapy for a mean duration of 3.5 years are presented. Fourteen received long term prednisone therapy for maintenance of disease suppression. All 16 have been asymptomatic or have had only mild symptoms which did not interfere with regular activities. Only 1 subject had to be rehospitalized. He subsequently underwent bowel surgery. Aternate day corticosteroid administration has been attained in 11 patients; 10 are growing and developing at a normal rate. In total, 13 of 16 have achieved pubertal development appropriate for age. The 8 patients with distal ileal disease have had a consistently excellent response to medical therapy. There have been no major adverse effects from drug therapy. It is concluded that an effort to suppress disease activity continuously in adolsecents with Crohn's disease is warranted. Excellent symptomatic control and normal rate of growth can be expected in patients with primarily ileal disease."}
{"id": "PMID:15919", "title": "[Effect of the cell dose on the development of 2 transplantable tumors in a syngeneic host].", "content": "The effects of different cell dose inoculation of plasmocitoma MOPC-315 and ADK-1t in Balb/c syngeneic mice are discussed in this work. Inoculated cell dose and neoplasia percent incidence have been noticed to be closely related, but unexpectedly two doses exist for each tumour, a comparatively small one and a definitely larger one, which cause nearly the same percent incidence. This paradox phenomenon is discussed also with reference to other researchers remarkers.", "contents": "[Effect of the cell dose on the development of 2 transplantable tumors in a syngeneic host]. The effects of different cell dose inoculation of plasmocitoma MOPC-315 and ADK-1t in Balb/c syngeneic mice are discussed in this work. Inoculated cell dose and neoplasia percent incidence have been noticed to be closely related, but unexpectedly two doses exist for each tumour, a comparatively small one and a definitely larger one, which cause nearly the same percent incidence. This paradox phenomenon is discussed also with reference to other researchers remarkers."}
{"id": "PMID:15923", "title": "[Programmed breech deliveries (author's transl)].", "content": "The question whether the termination of a breech pregnancy by a programmed breech delivery would reduce the fetal risk was investigated. In 71 of 433 singleton breech deliveries (16%) the breech delivery was induced by oxytocin infusion. There were 38 primigravidas and 33 multi-gravidas. The Apgar and pH values showed the same results as in 3904 vertex deliveries with spontaneous onset of labour. The duration of labour was shortened. The incidence of Caesarean Section in programmed breech deliveries was 9.86%. All 71 infants were mature and healthy. There were no perinatal deaths. The results show that the fetal risk in breech deliveries is reduced by programmed breech delivery to the same risk as in vertex deliveries with spontaneous onset of labour.", "contents": "[Programmed breech deliveries (author's transl)]. The question whether the termination of a breech pregnancy by a programmed breech delivery would reduce the fetal risk was investigated. In 71 of 433 singleton breech deliveries (16%) the breech delivery was induced by oxytocin infusion. There were 38 primigravidas and 33 multi-gravidas. The Apgar and pH values showed the same results as in 3904 vertex deliveries with spontaneous onset of labour. The duration of labour was shortened. The incidence of Caesarean Section in programmed breech deliveries was 9.86%. All 71 infants were mature and healthy. There were no perinatal deaths. The results show that the fetal risk in breech deliveries is reduced by programmed breech delivery to the same risk as in vertex deliveries with spontaneous onset of labour."}
{"id": "PMID:15931", "title": "Relationship between undissociated acidity of gastric juice and gastric protein secreted in response to graded doses of pentagastrin in duodenal ulcer patients.", "content": "Concentrations of free and total hydrogen ions, total protein and pepsin were measured in gastric juice fractions collected during basal secretion and upon stimulation by graded doses of pentagastrin administered intravenously. Undissociated hydrogen ion and non-pepsin protein concentrations were calculated as derived quantities. The studies were carried out in nine patients with duodenal ulcer both before and after truncal vagotomy. It was found that after vagotomy the undissociated hydrogen ion concentration was significantly lower and non-pepsin protein higher than before the operation. No correlation was found between the two quantities both before and after vagotomy. It was concluded that in duodenal ulcer patients either not all non-pepsin protein takes part in buffering of hydrogen ions secreted by parietal cells, or that non-protein buffers play a more important role.", "contents": "Relationship between undissociated acidity of gastric juice and gastric protein secreted in response to graded doses of pentagastrin in duodenal ulcer patients. Concentrations of free and total hydrogen ions, total protein and pepsin were measured in gastric juice fractions collected during basal secretion and upon stimulation by graded doses of pentagastrin administered intravenously. Undissociated hydrogen ion and non-pepsin protein concentrations were calculated as derived quantities. The studies were carried out in nine patients with duodenal ulcer both before and after truncal vagotomy. It was found that after vagotomy the undissociated hydrogen ion concentration was significantly lower and non-pepsin protein higher than before the operation. No correlation was found between the two quantities both before and after vagotomy. It was concluded that in duodenal ulcer patients either not all non-pepsin protein takes part in buffering of hydrogen ions secreted by parietal cells, or that non-protein buffers play a more important role."}
{"id": "PMID:15935", "title": "[Mycoses. Pathogenicity and diagnosis of dermatophytes, yeasts and molds].", "content": "Human beings today living in high industrialized areas suffer more frequently from fungal diseases than before. This is due to the management in animal production, but also to the use of cosmetics and contraceptives, smoking cigarettes, wearing clothes of synthetic polymers and application of new drugs, like antibiotics, cytostatics, immunosuppressives and others, which favours the growth of certain fungi in and on the skin and inside the human body. Some mechanisms are known from the macroorganism which are able to protect man from fungal invasion. Effective in this way are the normal flora of the skin, gut and the mucous membranes, the enzymes digestive and the natural low pH of the healthy skin. The fungal growths are favoured when primary diseases of not-infectious genesis due to disorders in metabolism or endocrinium, vitamin deficiency, malabsorption, maldigestion, false and malnutrition, and diseases of the haemopoetic system exist. But also viral and bacterial infections stimulate the development of secondary fungal diseases. The pathogens belong to three groups, dermatophytes, yeasts and molds, which can be differentiated according to their behaviour in culture and in tissue.", "contents": "[Mycoses. Pathogenicity and diagnosis of dermatophytes, yeasts and molds]. Human beings today living in high industrialized areas suffer more frequently from fungal diseases than before. This is due to the management in animal production, but also to the use of cosmetics and contraceptives, smoking cigarettes, wearing clothes of synthetic polymers and application of new drugs, like antibiotics, cytostatics, immunosuppressives and others, which favours the growth of certain fungi in and on the skin and inside the human body. Some mechanisms are known from the macroorganism which are able to protect man from fungal invasion. Effective in this way are the normal flora of the skin, gut and the mucous membranes, the enzymes digestive and the natural low pH of the healthy skin. The fungal growths are favoured when primary diseases of not-infectious genesis due to disorders in metabolism or endocrinium, vitamin deficiency, malabsorption, maldigestion, false and malnutrition, and diseases of the haemopoetic system exist. But also viral and bacterial infections stimulate the development of secondary fungal diseases. The pathogens belong to three groups, dermatophytes, yeasts and molds, which can be differentiated according to their behaviour in culture and in tissue."}
{"id": "PMID:15936", "title": "[Systemic immunologic diseases].", "content": "The systemic manifestation of immunological diseases is due to the spread of antigen mostly bound to specific antibody. Vasculitis and serositis follow the deposition of immune complexes to membranes. Whereas heterologous antigen causes temporary immune reactions, autologous antigen induces chronically reactions with definite destruction of tissue. Therefore, immunosuppression is indicated in autoaggressive diseases with rapid progrediency. In temporary reactions, however, antiphlogistic drugs and corticosteroids are sufficient.", "contents": "[Systemic immunologic diseases]. The systemic manifestation of immunological diseases is due to the spread of antigen mostly bound to specific antibody. Vasculitis and serositis follow the deposition of immune complexes to membranes. Whereas heterologous antigen causes temporary immune reactions, autologous antigen induces chronically reactions with definite destruction of tissue. Therefore, immunosuppression is indicated in autoaggressive diseases with rapid progrediency. In temporary reactions, however, antiphlogistic drugs and corticosteroids are sufficient."}
{"id": "PMID:15937", "title": "[Hormone producing gastrointestinal neoplasms].", "content": "1. Due to their common origin from the neural crest the hormonogenic cells of the intestinal tract show similar cyto-chemical and ultra-structural characteristics. 2. Hyperplasiae and tumors of these cells lead to excessive hormone production with its consequences on the reacting organs. 3. Hormone producing tumors can be confined to one organ only, but as multiple endocrine adenomatosis they can afflict several organs. 4. Diagnosis of most hormone producing tumors is possible with the adequate radio-immunologic tests. Radiologic and endoscopic examinations can contribute to the localization of the tumor. 5. Surgical resection of the tumor or of the reacting organs impaired by the overproduction of hormones from the tumor is the indicated therapy. Medicamentous therapy is rarely successful. 6. The growth of most hormonogenic tumors is relatively slow. Rates of survival of up to 30 years have been known, even after formation of metastases of the tumor. Effects of hormone overproduction on other organs can reduce the prognosis.", "contents": "[Hormone producing gastrointestinal neoplasms]. 1. Due to their common origin from the neural crest the hormonogenic cells of the intestinal tract show similar cyto-chemical and ultra-structural characteristics. 2. Hyperplasiae and tumors of these cells lead to excessive hormone production with its consequences on the reacting organs. 3. Hormone producing tumors can be confined to one organ only, but as multiple endocrine adenomatosis they can afflict several organs. 4. Diagnosis of most hormone producing tumors is possible with the adequate radio-immunologic tests. Radiologic and endoscopic examinations can contribute to the localization of the tumor. 5. Surgical resection of the tumor or of the reacting organs impaired by the overproduction of hormones from the tumor is the indicated therapy. Medicamentous therapy is rarely successful. 6. The growth of most hormonogenic tumors is relatively slow. Rates of survival of up to 30 years have been known, even after formation of metastases of the tumor. Effects of hormone overproduction on other organs can reduce the prognosis."}
{"id": "PMID:15939", "title": "The differential diagnosis of crescentic glomerulonephritis. The pathology of specific lesions with prognostic implications.", "content": "Combined findings from light and electron microscopy with immunofluorescence studies make a definitive diagnosis possible in most cases of crescentic glomerulonephritis. The patient's prognosis and pattern of response to therapy are matters of immediate concern in the light of recent developments in nephrology. The frequency of crescentic lesions varies depending on the specific types of disease, but the idiopathic lesion is seldom seen.", "contents": "The differential diagnosis of crescentic glomerulonephritis. The pathology of specific lesions with prognostic implications. Combined findings from light and electron microscopy with immunofluorescence studies make a definitive diagnosis possible in most cases of crescentic glomerulonephritis. The patient's prognosis and pattern of response to therapy are matters of immediate concern in the light of recent developments in nephrology. The frequency of crescentic lesions varies depending on the specific types of disease, but the idiopathic lesion is seldom seen."}
{"id": "PMID:15940", "title": "Three glucose 6-phosphate dehydrogenase variants found in Japan.", "content": "Three Japanese glucose 6-phosphate dehydrogenase (G6PD) variants were investigated. G6PD 'Mediterranean-like' had markedly decreased activity, normal electrophoretic mobility, low Km G6P, low Km NADP, increased utilization of all three substrate analogues (2-deoxy-G6P, Gal-6P, and deamino-NADP) and slightly decreased heat stability and slightly biphasic pH curve. G6PD 'Ogori' had markedly decreased activity, but otherwise normal characteristics. G6PD 'Hofu' had moderately decreased activity, normal electrophoretic mobility, slightly reduced Km G6P, normal Km NADP, normal utilization of 2-deoxy-G6P and Gal-6P, but increased utilization of deamino-NADP and normal heat stability as well as normal pH curve.", "contents": "Three glucose 6-phosphate dehydrogenase variants found in Japan. Three Japanese glucose 6-phosphate dehydrogenase (G6PD) variants were investigated. G6PD 'Mediterranean-like' had markedly decreased activity, normal electrophoretic mobility, low Km G6P, low Km NADP, increased utilization of all three substrate analogues (2-deoxy-G6P, Gal-6P, and deamino-NADP) and slightly decreased heat stability and slightly biphasic pH curve. G6PD 'Ogori' had markedly decreased activity, but otherwise normal characteristics. G6PD 'Hofu' had moderately decreased activity, normal electrophoretic mobility, slightly reduced Km G6P, normal Km NADP, normal utilization of 2-deoxy-G6P and Gal-6P, but increased utilization of deamino-NADP and normal heat stability as well as normal pH curve."}
{"id": "PMID:15941", "title": "Tissue culture propagation of tropical foliage plants.", "content": "Procedures were established for clonal multiplication in vitro of Cordyline terminalis Kunth, Dracaena godseffiana Hort., Scindapsus aureus Engler, and Syngonium podophyllum Schott. Shoot tips of actively growing terminals were selected as explants for Cordyline and Dracaena, and lateral buds were employed for Scindapsus and Syngonium. The basal nutrient medium contained Murashige and Skoog salts, 3% sucrose, 100 mg per 1 i-inositol, and 0.4 mg per 1 thiamine-HCl. The optima with respect to auxin, cytokinin, adenine sulfate-2H2O, and NaH2PO4-H2O addenda were determined. Also assessed were the influences of certain physical qualities of the nutrient medium and of the light intensity of the culture environment. The multiplication of each of the four plants was achieved by repeatedly subculturing the shoots that arose in vitro. Rates of plant increase per year per explant were calculated conservatively to be as follows: Syngonium, 5,000:Scindapsus, 100,000; Dracena, 300,000; and Cordyline, 500,000.", "contents": "Tissue culture propagation of tropical foliage plants. Procedures were established for clonal multiplication in vitro of Cordyline terminalis Kunth, Dracaena godseffiana Hort., Scindapsus aureus Engler, and Syngonium podophyllum Schott. Shoot tips of actively growing terminals were selected as explants for Cordyline and Dracaena, and lateral buds were employed for Scindapsus and Syngonium. The basal nutrient medium contained Murashige and Skoog salts, 3% sucrose, 100 mg per 1 i-inositol, and 0.4 mg per 1 thiamine-HCl. The optima with respect to auxin, cytokinin, adenine sulfate-2H2O, and NaH2PO4-H2O addenda were determined. Also assessed were the influences of certain physical qualities of the nutrient medium and of the light intensity of the culture environment. The multiplication of each of the four plants was achieved by repeatedly subculturing the shoots that arose in vitro. Rates of plant increase per year per explant were calculated conservatively to be as follows: Syngonium, 5,000:Scindapsus, 100,000; Dracena, 300,000; and Cordyline, 500,000."}
{"id": "PMID:15942", "title": "Early events in the induction of glutamine synthetase activity by hydrocortisone in embryonic chick neural retina.", "content": "Primary cultures of 10-day embryonic chick neural retinas were used to investigate early aspects of the mechanism of hydrocortisone action on glutamine synthetase activity. As little as 2 hr of hydrocortisone exposure served to initiate significant increases in the glutamine synthetase activity levels assayed after 24 hr culture. Time course studies indicated that the increase in glutamine synthetase activity observed after 24 hr in culture resulted from a two-phase rise in activity and that cycloheximide was effective in suppressing the second-phase rise. Additional inhibition studies demonstrated that the second-phase increase in enzyme activity required continuous protein synthesis during the initial 6 hr. The evidence suggests a mechanism of hydrocortisone action involving the production of a protein which is important for the induction of glutamine synthetase activity by hydrocortisone.", "contents": "Early events in the induction of glutamine synthetase activity by hydrocortisone in embryonic chick neural retina. Primary cultures of 10-day embryonic chick neural retinas were used to investigate early aspects of the mechanism of hydrocortisone action on glutamine synthetase activity. As little as 2 hr of hydrocortisone exposure served to initiate significant increases in the glutamine synthetase activity levels assayed after 24 hr culture. Time course studies indicated that the increase in glutamine synthetase activity observed after 24 hr in culture resulted from a two-phase rise in activity and that cycloheximide was effective in suppressing the second-phase rise. Additional inhibition studies demonstrated that the second-phase increase in enzyme activity required continuous protein synthesis during the initial 6 hr. The evidence suggests a mechanism of hydrocortisone action involving the production of a protein which is important for the induction of glutamine synthetase activity by hydrocortisone."}
{"id": "PMID:15945", "title": "Production of protease and elastase by Pseudomonas aeruginosa strains isolated from patients.", "content": "Using 20 strains of Pseudomonas aeruginosa isolated from patients, production of protease, elastase, and collagenase was determined by shaking culture in either complex or semisynthetic medium. No collagenase was produced by any strain of P. aeruginosa. According to their production of protease and elastase in different media, the P. aeruginosa strains were divided into three groups: the first group can produce elastase in complex medium and both protease and elastase in semisynthetic medium; the second group cannot produce any proteolytic enzymes in complex medium but can produce any proteolytic enzymes in either medium; and the third group cannot produce any proteolytic enzymes in either medium. In spite of the differences in the ability of the strains to produce the enzymes, depending upon the origin of the strains, the protease or elastases produced in different broths were regarded as identical.", "contents": "Production of protease and elastase by Pseudomonas aeruginosa strains isolated from patients. Using 20 strains of Pseudomonas aeruginosa isolated from patients, production of protease, elastase, and collagenase was determined by shaking culture in either complex or semisynthetic medium. No collagenase was produced by any strain of P. aeruginosa. According to their production of protease and elastase in different media, the P. aeruginosa strains were divided into three groups: the first group can produce elastase in complex medium and both protease and elastase in semisynthetic medium; the second group cannot produce any proteolytic enzymes in complex medium but can produce any proteolytic enzymes in either medium; and the third group cannot produce any proteolytic enzymes in either medium. In spite of the differences in the ability of the strains to produce the enzymes, depending upon the origin of the strains, the protease or elastases produced in different broths were regarded as identical."}
{"id": "PMID:15946", "title": "Antibacterial product of peritoneal exudate cell cultures from guinea pigs infected with mycobacteria, listeriae, and rickettsiae.", "content": "In an in vitro model of cellular immunity, the antibacterial product of immunologically mediated mononuclear cell activation was studied from guinea pigs infected with listeriae and rickettsiae and compared with the product previously described from animals infected with mycobacteria. We found that this product, active against gram-positive bacilli, appeared to be  identical in the three different infections with regard to its heat stability, its chromatographic adsorption and elution pattern, its susceptibility to inactivation by proteolytic enzymes, and its antibacterial spectrum", "contents": "Antibacterial product of peritoneal exudate cell cultures from guinea pigs infected with mycobacteria, listeriae, and rickettsiae. In an in vitro model of cellular immunity, the antibacterial product of immunologically mediated mononuclear cell activation was studied from guinea pigs infected with listeriae and rickettsiae and compared with the product previously described from animals infected with mycobacteria. We found that this product, active against gram-positive bacilli, appeared to be  identical in the three different infections with regard to its heat stability, its chromatographic adsorption and elution pattern, its susceptibility to inactivation by proteolytic enzymes, and its antibacterial spectrum"}
{"id": "PMID:15947", "title": "Nutrition and enterotoxin synthesis by enterotoxigenic strains of Escherichia coli: defined medium for production of heat-stable enterotoxin.", "content": "A defined medium has been developed which supports synthesis of heat-stable enterotoxin (ST) by porcine and bovine strains of enterotoxigenic (ENT+) Escherichia coli in levels equivalent or better than a complex Casamino Acids-salts medium. The medium components did not support production of heat-labile enterotoxin (LT) but were similar for ST synthesis by ENT+ strains producting only ST and those which produced ST in addition to LT. The amino acids in Casamino Acids found to be necessary for growth and enterotoxin synthesis were proline, serine, aspartic acid, and alanine. Maximal growth and toxin levels were obtained after 8 h of incubation. Improved growth, but not an increase in synthesis of ST, was observed in the presence of Mg2+, Mn2+ and Fe3+ compared with Mg2+ alone. A chelator, tricine, was necessary for maximal cell densities,, probably to solubilize trace ions and make them more available to the bacteria. Increased growth was observed upon addition of glucose to both complex and defined media; however, glucose as well as gluconate and pyruvate appeared to cause repression of toxin synthesis. Addition of vitamins, oleic acid, or DL-lactic acid to the defined medium slightly increased levels of ST.", "contents": "Nutrition and enterotoxin synthesis by enterotoxigenic strains of Escherichia coli: defined medium for production of heat-stable enterotoxin. A defined medium has been developed which supports synthesis of heat-stable enterotoxin (ST) by porcine and bovine strains of enterotoxigenic (ENT+) Escherichia coli in levels equivalent or better than a complex Casamino Acids-salts medium. The medium components did not support production of heat-labile enterotoxin (LT) but were similar for ST synthesis by ENT+ strains producting only ST and those which produced ST in addition to LT. The amino acids in Casamino Acids found to be necessary for growth and enterotoxin synthesis were proline, serine, aspartic acid, and alanine. Maximal growth and toxin levels were obtained after 8 h of incubation. Improved growth, but not an increase in synthesis of ST, was observed in the presence of Mg2+, Mn2+ and Fe3+ compared with Mg2+ alone. A chelator, tricine, was necessary for maximal cell densities,, probably to solubilize trace ions and make them more available to the bacteria. Increased growth was observed upon addition of glucose to both complex and defined media; however, glucose as well as gluconate and pyruvate appeared to cause repression of toxin synthesis. Addition of vitamins, oleic acid, or DL-lactic acid to the defined medium slightly increased levels of ST."}
{"id": "PMID:15948", "title": "Osteomyelitis caused by mycobacterium fortuitum.", "content": "A case of osteomylitis of the foot and ankle bones with subsequent complications is presented. Antibiotic therapy was unsuccessful and a below-knee amputation was performed. A comparison of the various Mycobacteria species and their role as etiologic agents in osteomyelitis follows.", "contents": "Osteomyelitis caused by mycobacterium fortuitum. A case of osteomylitis of the foot and ankle bones with subsequent complications is presented. Antibiotic therapy was unsuccessful and a below-knee amputation was performed. A comparison of the various Mycobacteria species and their role as etiologic agents in osteomyelitis follows."}
{"id": "PMID:15949", "title": "The effects of anesthetic drugs and disease on the chemical regulation of ventilation.", "content": "The anesthesiologist uses a wide spectrum of drugs, including inhalational general anesthetics, barbiturates, benzodiazepines, narcotics analgesics and their antagonists, and neuromuscular blocking drugs. All of these drugs in sufficient dose impair the ventilatory response to chemical stimuli, and may cause inadequate gas exchange. The effect of depression of ventilatory control depends on the magnitude of depression and the coexistence of functional abnormalities in the respiratory system. The functional abnormalities are the result of preexistent pulmonary disease or other disease processes that impair respiratory function, the anticipated effects of major surgery (e.g., pulmonary resection), and the complications of anesthesia and surgery. From a functional viewpoint, the mechanisms of the effects of these disease processes on ventilatory control are: (1) interference with the neurophysiological control of automatic ventilation; (2) impairment of peripheral or central chemoreceptor function; (3) impairment of respiratory muscle function; (4) increase in the mechanical load to breathing as a result of increased resistance or decreased compliance of the respiratory system; and (5) increase in the ventilatory requirements as a result of ventilation/blood flow maldistribution, metabolic acidosis, or increased metabolic rate. As a result of current trends in the use of multiple drugs and controlled ventilation during anesthesia, the patient is at greatest risk during the early postoperative period in the recovery room. In addition to the functional abnormalities described above, the probability of impaired gas exchange and respiratory failure is increased as a result of impaired metabolism and elimination of drugs as a result of hepatic and renal insufficiency, and acute changes in acidbase status, which alter the ionization and distribution of drugs.", "contents": "The effects of anesthetic drugs and disease on the chemical regulation of ventilation. The anesthesiologist uses a wide spectrum of drugs, including inhalational general anesthetics, barbiturates, benzodiazepines, narcotics analgesics and their antagonists, and neuromuscular blocking drugs. All of these drugs in sufficient dose impair the ventilatory response to chemical stimuli, and may cause inadequate gas exchange. The effect of depression of ventilatory control depends on the magnitude of depression and the coexistence of functional abnormalities in the respiratory system. The functional abnormalities are the result of preexistent pulmonary disease or other disease processes that impair respiratory function, the anticipated effects of major surgery (e.g., pulmonary resection), and the complications of anesthesia and surgery. From a functional viewpoint, the mechanisms of the effects of these disease processes on ventilatory control are: (1) interference with the neurophysiological control of automatic ventilation; (2) impairment of peripheral or central chemoreceptor function; (3) impairment of respiratory muscle function; (4) increase in the mechanical load to breathing as a result of increased resistance or decreased compliance of the respiratory system; and (5) increase in the ventilatory requirements as a result of ventilation/blood flow maldistribution, metabolic acidosis, or increased metabolic rate. As a result of current trends in the use of multiple drugs and controlled ventilation during anesthesia, the patient is at greatest risk during the early postoperative period in the recovery room. In addition to the functional abnormalities described above, the probability of impaired gas exchange and respiratory failure is increased as a result of impaired metabolism and elimination of drugs as a result of hepatic and renal insufficiency, and acute changes in acidbase status, which alter the ionization and distribution of drugs."}
{"id": "PMID:15951", "title": "Biochemical and physiological approaches to opiate dependence.", "content": "Biochemical and physiological theories of opiate addiction are reviewed in an historical context. The biochemical evidence implicating acetylcholine and norepinephrine in the phenomena of tolerance and physical dependence is described, and the six major biochemical and physiological theories are reviewed, emphasizing their close ties (differing sometimes only linguistically) with late nineteenth century theories of tolerance and physical dependence. The operational-reductionistic approaches taken by these theorists, especially when defining psychic dependence, is criticized from a phenomenological point of view while also emphasizing that characteristics of the social structure and moral viewpoints must also be taken into account when studying these phenomena.", "contents": "Biochemical and physiological approaches to opiate dependence. Biochemical and physiological theories of opiate addiction are reviewed in an historical context. The biochemical evidence implicating acetylcholine and norepinephrine in the phenomena of tolerance and physical dependence is described, and the six major biochemical and physiological theories are reviewed, emphasizing their close ties (differing sometimes only linguistically) with late nineteenth century theories of tolerance and physical dependence. The operational-reductionistic approaches taken by these theorists, especially when defining psychic dependence, is criticized from a phenomenological point of view while also emphasizing that characteristics of the social structure and moral viewpoints must also be taken into account when studying these phenomena."}
{"id": "PMID:15952", "title": "The activation of intravascular coagulation by bromocarbamide.", "content": "In the rabbit the application of a non-lethal, sleep-inducing dose of bromisovalerianyl carbamide (0.5 g/kg body weight) causes an activation of the coagulation system. This activation is manifested by shortened thrombin and partial thromboplastin times and a decrease of fibrinogen concentration and Factor V activity. In contrast, pentobarbital sodium at a dose (62.5 mg/kg) which causes the same changes in arterial partial oxygen pressure and arterial pH does not influence the coagulation system. The bromocarbamide-induced changes in the coagulation system are not to be considered as a result of hypoxia and acidosis but seem to be caused by early endothelial and tissue lesions which result in the release of procoagulatory substances. In healthy test persons a single dose of 1.5 g bromisovalerianyl carbamide has no demonstrable influence on the system of hemostasis.", "contents": "The activation of intravascular coagulation by bromocarbamide. In the rabbit the application of a non-lethal, sleep-inducing dose of bromisovalerianyl carbamide (0.5 g/kg body weight) causes an activation of the coagulation system. This activation is manifested by shortened thrombin and partial thromboplastin times and a decrease of fibrinogen concentration and Factor V activity. In contrast, pentobarbital sodium at a dose (62.5 mg/kg) which causes the same changes in arterial partial oxygen pressure and arterial pH does not influence the coagulation system. The bromocarbamide-induced changes in the coagulation system are not to be considered as a result of hypoxia and acidosis but seem to be caused by early endothelial and tissue lesions which result in the release of procoagulatory substances. In healthy test persons a single dose of 1.5 g bromisovalerianyl carbamide has no demonstrable influence on the system of hemostasis."}
{"id": "PMID:15955", "title": "Hormonal control of zinc uptake and binding in the rat dorsolateral prostate.", "content": "The zinc uptake in the dorsolateral prostate of rats was studied after different hormonal manipulations. Orchiectomy reduced the uptake of 65Zn. Administration of estradiol benzoate to orchiectomized rats doubled the 65Zn uptake, a phenomenon which was not observed in orchiectomized-adrenalectomized rats. Adrenalectomy in orchiectomized rats had no effect on the concentration of radioactivity beyond the castration-induced decrease. A prolactin release inhibitor, 6-methyl-8-erogelenylacetamide, reduced the radioactivity concentration without changing the weight of the gland. Cyproterone acetate reduced the weight but not the radioactivity concentration. The concentration of 65Zn in the ventral prostate was not changed by orchiectomy, adrenalectomy, or the administration of estradiol benzoate, prolactin release inhibiors, or cyproterone acetate. The results suggest an important role for prolactin in the zinc uptake in the dorsolateral prostate but not in the ventral prostate.", "contents": "Hormonal control of zinc uptake and binding in the rat dorsolateral prostate. The zinc uptake in the dorsolateral prostate of rats was studied after different hormonal manipulations. Orchiectomy reduced the uptake of 65Zn. Administration of estradiol benzoate to orchiectomized rats doubled the 65Zn uptake, a phenomenon which was not observed in orchiectomized-adrenalectomized rats. Adrenalectomy in orchiectomized rats had no effect on the concentration of radioactivity beyond the castration-induced decrease. A prolactin release inhibitor, 6-methyl-8-erogelenylacetamide, reduced the radioactivity concentration without changing the weight of the gland. Cyproterone acetate reduced the weight but not the radioactivity concentration. The concentration of 65Zn in the ventral prostate was not changed by orchiectomy, adrenalectomy, or the administration of estradiol benzoate, prolactin release inhibiors, or cyproterone acetate. The results suggest an important role for prolactin in the zinc uptake in the dorsolateral prostate but not in the ventral prostate."}
{"id": "PMID:15956", "title": "Plasma constituent (s) inhibiting platelet adhesiveness.", "content": "Adhesiveness in citrated whole blood is critically pH dependent at hydrogenion concentrations close to the physiological range. While platelets in platelet-rich plasma (PRP) adhere poorly in glass-bead columns, washed platelets and particularly gel-filtered platelets (GFP), prepared from PRP, are adhesive, Separation of PRP on a Sepharose 2B column revealed the presence of an inhibitor of adhesiveness of GFP. The inhibitory compound is thermostable and nondialyzable. It is inactivated completely by pronase digestion and partally by trypsin digestion. It is distinct from any one of the known platelet factors. Washed erythrocytes and erythrocyte membranes attenuate the potency of the inhibitor. Following separation by isoelectric focusing, the inhibitory activity is limited primarily to a single fraction with an isoelectric point of 5.1 containing equal amounts of proteins and lipids. Two protein bands are revealed by sodium dodecyl sulfate-gel electrophoresis of the purified fraction. It is concluded that PRP contains a compound, apparently a lipoprotein, which inhibits platelet adhesiveness.", "contents": "Plasma constituent (s) inhibiting platelet adhesiveness. Adhesiveness in citrated whole blood is critically pH dependent at hydrogenion concentrations close to the physiological range. While platelets in platelet-rich plasma (PRP) adhere poorly in glass-bead columns, washed platelets and particularly gel-filtered platelets (GFP), prepared from PRP, are adhesive, Separation of PRP on a Sepharose 2B column revealed the presence of an inhibitor of adhesiveness of GFP. The inhibitory compound is thermostable and nondialyzable. It is inactivated completely by pronase digestion and partally by trypsin digestion. It is distinct from any one of the known platelet factors. Washed erythrocytes and erythrocyte membranes attenuate the potency of the inhibitor. Following separation by isoelectric focusing, the inhibitory activity is limited primarily to a single fraction with an isoelectric point of 5.1 containing equal amounts of proteins and lipids. Two protein bands are revealed by sodium dodecyl sulfate-gel electrophoresis of the purified fraction. It is concluded that PRP contains a compound, apparently a lipoprotein, which inhibits platelet adhesiveness."}
{"id": "PMID:15957", "title": "[Immunosuppressive agents for therapy of autoimmune diseases of the skin and of psoriasis].", "content": "A review of immunosuppressive therapy of dermatoses is given. The pathogenesis of autoimmun diseases is discussed. The treatment of autoimmun diseases and of psoriasis with immunosuppressive drugs is ilucidated.", "contents": "[Immunosuppressive agents for therapy of autoimmune diseases of the skin and of psoriasis]. A review of immunosuppressive therapy of dermatoses is given. The pathogenesis of autoimmun diseases is discussed. The treatment of autoimmun diseases and of psoriasis with immunosuppressive drugs is ilucidated."}
{"id": "PMID:15960", "title": "The hospitalized child with urticaria.", "content": "Patients with urticaria and angioedema admitted to CHMC were analyzed. The most common etiologic factor for the urticaria was infection (in 45% of the cases), while drugs or medications were responsible in 10% of patients. Almost half of the children received corticosteroids for the treatment of their urticaria.", "contents": "The hospitalized child with urticaria. Patients with urticaria and angioedema admitted to CHMC were analyzed. The most common etiologic factor for the urticaria was infection (in 45% of the cases), while drugs or medications were responsible in 10% of patients. Almost half of the children received corticosteroids for the treatment of their urticaria."}
{"id": "PMID:15974", "title": "Formation and dissimilation of oxalacetate and pyruvate Pseudomonas citronellolis grown on noncarbohydrate substrates.", "content": "Metabolism of lactate as a carbon source by Pseudomonas citronellolis occurred via a nicotinamide adenine dinucleotide (NAD)-independent L-lactate dehydrogenase, which was present in cells grown on DL-lactate but was not present in cells grown on acetate, aspartate, citrate, glucose, glutamate, or malate. The cells also possessed a constitutive, NAD-independent malate dehydrogenase instead of the conventional NAD-dependent malate dehydrogenase instead of the conventional NAD-dependent enzyme in the tricarboxylic acid cycle. Both enzymes were particulate and used dichlorophenolindo-phenol or oxygen as an electron acceptor. In acetate-grown cells, the activity of pyruvate dehydrogenase and NAD phosphate-linked malate enzyme decreased, cells grown on glucose or lactate. This was consistent with the need to maintain a supply of oxalacetate for metabolism of acetate via the tricarboxylic acid cycle. Changes in enzyme activities suggest that gluconeogenesis from noncarbohydrate carbon sources occurs via the malate enzyme (when oxalacetate decarboxylase is inhibited) or a combination of the NAD-independent malate dehydrogenase and oxalacetate decarboxylase.", "contents": "Formation and dissimilation of oxalacetate and pyruvate Pseudomonas citronellolis grown on noncarbohydrate substrates. Metabolism of lactate as a carbon source by Pseudomonas citronellolis occurred via a nicotinamide adenine dinucleotide (NAD)-independent L-lactate dehydrogenase, which was present in cells grown on DL-lactate but was not present in cells grown on acetate, aspartate, citrate, glucose, glutamate, or malate. The cells also possessed a constitutive, NAD-independent malate dehydrogenase instead of the conventional NAD-dependent malate dehydrogenase instead of the conventional NAD-dependent enzyme in the tricarboxylic acid cycle. Both enzymes were particulate and used dichlorophenolindo-phenol or oxygen as an electron acceptor. In acetate-grown cells, the activity of pyruvate dehydrogenase and NAD phosphate-linked malate enzyme decreased, cells grown on glucose or lactate. This was consistent with the need to maintain a supply of oxalacetate for metabolism of acetate via the tricarboxylic acid cycle. Changes in enzyme activities suggest that gluconeogenesis from noncarbohydrate carbon sources occurs via the malate enzyme (when oxalacetate decarboxylase is inhibited) or a combination of the NAD-independent malate dehydrogenase and oxalacetate decarboxylase."}
{"id": "PMID:15975", "title": "Cellulase of Neurospora crassa.", "content": "Mycelia and ungerminated conidia of Neurospora crassa were found to secrete extracellular endocellulase (EC 3.2.1.4). A simple induction system of potassium phosphate buffer (ph 6.0) plus inducer relied on the internal metabolic reserves of conicia or mycelia to provide energy and substrates for protein synthesis. Buffer concentration for optimum enzyme production was 100 mM, but at higher buffer concentrations enzyme production was inhibited. Cellobiose was clearly the best inducer, with an optimum effect from 0.05 to 1 mM. In deionized water, cellulase remained mostly associated with the cell, but a variety of salts stimulated the release of cellulase into the medium.", "contents": "Cellulase of Neurospora crassa. Mycelia and ungerminated conidia of Neurospora crassa were found to secrete extracellular endocellulase (EC 3.2.1.4). A simple induction system of potassium phosphate buffer (ph 6.0) plus inducer relied on the internal metabolic reserves of conicia or mycelia to provide energy and substrates for protein synthesis. Buffer concentration for optimum enzyme production was 100 mM, but at higher buffer concentrations enzyme production was inhibited. Cellobiose was clearly the best inducer, with an optimum effect from 0.05 to 1 mM. In deionized water, cellulase remained mostly associated with the cell, but a variety of salts stimulated the release of cellulase into the medium."}
{"id": "PMID:15976", "title": "Phosphoribulokinase from Nitrobacter winogradskyi: activation by reduced nicotinamide adenine dinucleotide and inhibition by pyridoxal phosphate.", "content": "CO2 fixation by particle-free extracts from Nitrobacter winogradskyi increased by addition of reduced nicotinamide adenine dinucleotide (NADH). Ribulose-1,5-diphosphate, however, increased CO2 fixation, even in the absence of NADH. Phosphoribulokinase (EC 2.7.1.19) was the enzyme of Nitrobacter extracts that was activated specifically by NADH. Pyridoxal-5-phosphate inhibited both CO2 fixation and NADH-activated phosphoribulokinase from Nitrobacter. However, it did not affect phosphoribulokinase from spinach leaves. Since the spinach enzyme had also no requirement for reduced pyridine nucleotides, it appears that pyridoxal phosphate interferes only with the binding of NADH and not with the binding of ribulose-5-phosphate and adenosine-5'-triphosphate. The regulation of phosphoribulokinase activity by NADH provided Nitrobacter with an energy-dependent control mechanism of CO2 assimilation.", "contents": "Phosphoribulokinase from Nitrobacter winogradskyi: activation by reduced nicotinamide adenine dinucleotide and inhibition by pyridoxal phosphate. CO2 fixation by particle-free extracts from Nitrobacter winogradskyi increased by addition of reduced nicotinamide adenine dinucleotide (NADH). Ribulose-1,5-diphosphate, however, increased CO2 fixation, even in the absence of NADH. Phosphoribulokinase (EC 2.7.1.19) was the enzyme of Nitrobacter extracts that was activated specifically by NADH. Pyridoxal-5-phosphate inhibited both CO2 fixation and NADH-activated phosphoribulokinase from Nitrobacter. However, it did not affect phosphoribulokinase from spinach leaves. Since the spinach enzyme had also no requirement for reduced pyridine nucleotides, it appears that pyridoxal phosphate interferes only with the binding of NADH and not with the binding of ribulose-5-phosphate and adenosine-5'-triphosphate. The regulation of phosphoribulokinase activity by NADH provided Nitrobacter with an energy-dependent control mechanism of CO2 assimilation."}
{"id": "PMID:15977", "title": "Extracellular phosphatases of Chlamydomonas reinhardi and their regulation.", "content": "Chlamydomonas reinhardi, cultured under normal growth conditions, secreted significant amounts of protein and carbohydrates but not lipids or nucleic acids. A fivefold increase in light intensity led to a tenfold increase in secreted protein and carbohydrate. Among the proteins secreted was acid phosphatase with a pH optimum at 4.8 like the enzyme in the cells. Phosphorus depleted algae grown on minimal orthophosphate contained and secreted both acid and alkaline phosphatase. The pH optimum of the intracellular alkaline phosphatase was 9.2. When phosphorus-depleted cells were grown with increasing orthophosphate, intra- and extracellular alkaline phosphatase was almost completely repressed and intra- and extracellular acid phosphatase was partially repressed. Extracellular acid and alkaline phosphatase increased with the age of the culture. Electrophoresis indicated only one acid and one alkaline phosphatase in phosphorus-satisfied and phosphorus-depleted cells. Chlamydomonas cells suspended in an inorganic salt solution secreted only acid phosphatase; the absence of any extr-cellular cytoplasmic marker enzyme indicated that there was little, if any, autolysis to account for the extracellular acid enzyme. Phosphorus-depleted cells were able to grow on organic phosphates as the sole source of orthophosphate. Ribose-5-phosphate was the best for cell multiplication, and its utility was shown to be due to the cell's ability to use the ribose as well as the orthophosphatase for cell multiplication.", "contents": "Extracellular phosphatases of Chlamydomonas reinhardi and their regulation. Chlamydomonas reinhardi, cultured under normal growth conditions, secreted significant amounts of protein and carbohydrates but not lipids or nucleic acids. A fivefold increase in light intensity led to a tenfold increase in secreted protein and carbohydrate. Among the proteins secreted was acid phosphatase with a pH optimum at 4.8 like the enzyme in the cells. Phosphorus depleted algae grown on minimal orthophosphate contained and secreted both acid and alkaline phosphatase. The pH optimum of the intracellular alkaline phosphatase was 9.2. When phosphorus-depleted cells were grown with increasing orthophosphate, intra- and extracellular alkaline phosphatase was almost completely repressed and intra- and extracellular acid phosphatase was partially repressed. Extracellular acid and alkaline phosphatase increased with the age of the culture. Electrophoresis indicated only one acid and one alkaline phosphatase in phosphorus-satisfied and phosphorus-depleted cells. Chlamydomonas cells suspended in an inorganic salt solution secreted only acid phosphatase; the absence of any extr-cellular cytoplasmic marker enzyme indicated that there was little, if any, autolysis to account for the extracellular acid enzyme. Phosphorus-depleted cells were able to grow on organic phosphates as the sole source of orthophosphate. Ribose-5-phosphate was the best for cell multiplication, and its utility was shown to be due to the cell's ability to use the ribose as well as the orthophosphatase for cell multiplication."}
{"id": "PMID:15978", "title": "Alkaline phosphatase of Blastocladiella emersonii: partial purification and characterization.", "content": "Alkaline phosphomonoesterase (EC 3.1.3.1) activity from Blastocladiella emersonii, while displaying typically broad substrate specificity for phosphorylated organic compounds, exhibited nearly complete substrate preference for N-acetylglucosamine-6-phosphate over N-acetylglucosamine-1-phosphate. Enzyme in zoospore extracts was purified 43-fold by differential centrifugation followed by gel filtration (Sephadex G-200) and then by ion-exchange chromatography (diethylaminoethyl-cellulose). The partially purified enzyme displayed an apparent molecular weight (Sephadex G-200) of approximately 170,000. The activity of partially purified enzyme exhibited a pH optimum of pH 8.5, did not require a metal divalent cation, but was inhibitable by ethylenediaminetetraacetic acid. During the life cycle of the organism, the specific activity of the phosphatase decreased slightly during germination and early exponential growth but then increased about 4.5-fold during sporulation. B. emersonii alkaline phosphatase does not appear to be a repressible enzyme.", "contents": "Alkaline phosphatase of Blastocladiella emersonii: partial purification and characterization. Alkaline phosphomonoesterase (EC 3.1.3.1) activity from Blastocladiella emersonii, while displaying typically broad substrate specificity for phosphorylated organic compounds, exhibited nearly complete substrate preference for N-acetylglucosamine-6-phosphate over N-acetylglucosamine-1-phosphate. Enzyme in zoospore extracts was purified 43-fold by differential centrifugation followed by gel filtration (Sephadex G-200) and then by ion-exchange chromatography (diethylaminoethyl-cellulose). The partially purified enzyme displayed an apparent molecular weight (Sephadex G-200) of approximately 170,000. The activity of partially purified enzyme exhibited a pH optimum of pH 8.5, did not require a metal divalent cation, but was inhibitable by ethylenediaminetetraacetic acid. During the life cycle of the organism, the specific activity of the phosphatase decreased slightly during germination and early exponential growth but then increased about 4.5-fold during sporulation. B. emersonii alkaline phosphatase does not appear to be a repressible enzyme."}
{"id": "PMID:15979", "title": "Effects of carbon dioxide, urea, and ammonia on growth of Ureaplasma urealyticum (T-strain mycoplasma).", "content": "By use of a simple device for continuous CO2 gassing of Ureaplasma urealyticum cultures growing in a liquid medium, we have been able to separate some of the effects of urea, CO2, ammonia, and pH on growth. The CO2 acted as a superior buffer in the pH range 5.7 to 6.8, which is optimal for Ureaplasma growth. It was, therefore, possible to observe the effect of repeated additions of urea to the culture without alkalinization of the growth medium. We found that the repeated additions of urea did not enhance Ureaplasma growth, and the resultant accumulation of ammonium ions (greater than 2,000 microng/ml) did not cause more rapid death under these conditions. By abruptly changing the gaseous environment from CO2 to N2, it was possible to cause a rapid pH change in the culture to a value above 8.0. This resulted in a more rapid death of the organisms.", "contents": "Effects of carbon dioxide, urea, and ammonia on growth of Ureaplasma urealyticum (T-strain mycoplasma). By use of a simple device for continuous CO2 gassing of Ureaplasma urealyticum cultures growing in a liquid medium, we have been able to separate some of the effects of urea, CO2, ammonia, and pH on growth. The CO2 acted as a superior buffer in the pH range 5.7 to 6.8, which is optimal for Ureaplasma growth. It was, therefore, possible to observe the effect of repeated additions of urea to the culture without alkalinization of the growth medium. We found that the repeated additions of urea did not enhance Ureaplasma growth, and the resultant accumulation of ammonium ions (greater than 2,000 microng/ml) did not cause more rapid death under these conditions. By abruptly changing the gaseous environment from CO2 to N2, it was possible to cause a rapid pH change in the culture to a value above 8.0. This resulted in a more rapid death of the organisms."}
{"id": "PMID:15980", "title": "Localization of enzymes in Ureaplasma urealyticum (T-strain mycoplasma).", "content": "Ureaplasma urealyticum cells were lysed by osmotic shock or by digitonin. The membrane fraction contained four to ten times as much protein as the cytoplasmic fraction. These values are in large excess of those reported for classical mycoplasmas, suggesting that the Ureaplasma membrane fraction was heavily contaminated with proteins derived from the growth medium. The U. urealyticum urease activity was localized in the cytoplasmic fraction, whereas the adenosine triphosphatase activity was localized in the membrane fraction. Significant urease activity could be detected also in nonviable cells. Urea, at concentrations above 0.25 M, was mycoplasmastatic to Acholeplasma laidlawii, Mycoplasma hominis, and U. urealyticum, so that the Ureaplasma urease did not afford preferential protection against urea toxicity. The intracellular localization of the urease would be expected to release ammonia from urea in the cytoplasm. The ammonia will take up protons to become ammonium ions. It can be hypothesized that the intracellular NH4+ plays a role in proton elimination or acid-base balance, which might be coupled to an energy producing ion gradient and/or transport mechanisms.", "contents": "Localization of enzymes in Ureaplasma urealyticum (T-strain mycoplasma). Ureaplasma urealyticum cells were lysed by osmotic shock or by digitonin. The membrane fraction contained four to ten times as much protein as the cytoplasmic fraction. These values are in large excess of those reported for classical mycoplasmas, suggesting that the Ureaplasma membrane fraction was heavily contaminated with proteins derived from the growth medium. The U. urealyticum urease activity was localized in the cytoplasmic fraction, whereas the adenosine triphosphatase activity was localized in the membrane fraction. Significant urease activity could be detected also in nonviable cells. Urea, at concentrations above 0.25 M, was mycoplasmastatic to Acholeplasma laidlawii, Mycoplasma hominis, and U. urealyticum, so that the Ureaplasma urease did not afford preferential protection against urea toxicity. The intracellular localization of the urease would be expected to release ammonia from urea in the cytoplasm. The ammonia will take up protons to become ammonium ions. It can be hypothesized that the intracellular NH4+ plays a role in proton elimination or acid-base balance, which might be coupled to an energy producing ion gradient and/or transport mechanisms."}
{"id": "PMID:15981", "title": "Cell envelope protection of alkaline phosphatase against acid denaturation in Escherichia coli.", "content": "The effects of a highly acidic environment on the cell-associated alkaline phosphatase activities of a smooth and a rough strain of Escherichia coli O8 have been examined. The observation that cell-associated enzyme is denatured to a lesser degree than purified enzyme suggests that the association of the enzyme with the cell envelope affords it some degree of protection from potentially disruptive agents in the environment. The degree of protection afforded the enzyme from pH denaturation appears to be dependent upon the presence of a complete lipopolysaccharide in the outer membrane of these strains. An abbreviation of the chemical structure of this cell envelope component produces a change in the outer membrane, resulting in increased susceptibility of the cells to a battery of antibiotics and to lysozyme and in a small, but significant, change in the sensitivity of the cell envelope-associated alkaline phosphatase to the denaturing effect of an acidic environment.", "contents": "Cell envelope protection of alkaline phosphatase against acid denaturation in Escherichia coli. The effects of a highly acidic environment on the cell-associated alkaline phosphatase activities of a smooth and a rough strain of Escherichia coli O8 have been examined. The observation that cell-associated enzyme is denatured to a lesser degree than purified enzyme suggests that the association of the enzyme with the cell envelope affords it some degree of protection from potentially disruptive agents in the environment. The degree of protection afforded the enzyme from pH denaturation appears to be dependent upon the presence of a complete lipopolysaccharide in the outer membrane of these strains. An abbreviation of the chemical structure of this cell envelope component produces a change in the outer membrane, resulting in increased susceptibility of the cells to a battery of antibiotics and to lysozyme and in a small, but significant, change in the sensitivity of the cell envelope-associated alkaline phosphatase to the denaturing effect of an acidic environment."}
{"id": "PMID:15982", "title": "Properties of two phosphatases and a cyclic phosphodiesterase of Salmonella typhimurium.", "content": "The properties of three phosphatases from Salmonella typhimurium have been examined. A cyclic 2',3'-nucleotide phosphodiesterase (EC 3.1.4.d) hydrolyzes cyclic 2',3'-purine and -pyrimidine nucleotides, as well as 3'-mononucleotides, and has a pH optimum of about 7.5. It requires divalent cations for activity and has a molecular weight of 67,000. Acid hexose phosphatase (EC 3.1.2.2) possesses activity towards hexose phosphates as well as other sugar phosphates. The enzyme is apparently a dimer of 37,000-dalton subunits. Nonspecific acid phosphatase (EC 3.1.3.2) hydrolyzes a variety of phosphate esters, including nucleotides and sugar phosphates. The enzyme also hydrolyzes the phosphoric anhydride bonds of pyrophosphate and nucleotides. Michaelis constants of the nonspecific acid phosphatase for several of its substrates are in the 1 to 2 mM range. Nonspecific acid phosphatase is a dimer of 27,000-dalton subunits.", "contents": "Properties of two phosphatases and a cyclic phosphodiesterase of Salmonella typhimurium. The properties of three phosphatases from Salmonella typhimurium have been examined. A cyclic 2',3'-nucleotide phosphodiesterase (EC 3.1.4.d) hydrolyzes cyclic 2',3'-purine and -pyrimidine nucleotides, as well as 3'-mononucleotides, and has a pH optimum of about 7.5. It requires divalent cations for activity and has a molecular weight of 67,000. Acid hexose phosphatase (EC 3.1.2.2) possesses activity towards hexose phosphates as well as other sugar phosphates. The enzyme is apparently a dimer of 37,000-dalton subunits. Nonspecific acid phosphatase (EC 3.1.3.2) hydrolyzes a variety of phosphate esters, including nucleotides and sugar phosphates. The enzyme also hydrolyzes the phosphoric anhydride bonds of pyrophosphate and nucleotides. Michaelis constants of the nonspecific acid phosphatase for several of its substrates are in the 1 to 2 mM range. Nonspecific acid phosphatase is a dimer of 27,000-dalton subunits."}
{"id": "PMID:15983", "title": "Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases.", "content": "Two new mutations are described which, together, eliminate essentially all the aminotransferase activity required for de novo biosynthesis of tyrosine, phenylalanine, and aspartic acid in a K-12 strain of Escherichia coli. One mutation, designated tyrB, lies at about 80 min on the E. coli map and inactivates the \"tyrosine-repressible\" tyrosine/phenylalanine aminotransferase. The second mutation, aspC, maps at about 20 min and inactivates a nonrespressible aspartate aminotransferase that also has activity on the aromatic amino acids. In ilvE- strains, which lack the branched-chain amino acid aminotransferase, the presence of either the tyrosine-repressible aminotransferase or the aspartate aminotransferase is sufficient for growth in the absence of exogenous tyrosine, phenylalanine, or aspartate; the tyrosine-repressible enzyme is also active in leucine biosynthesis. The ilvE gene product alone can reverse a phenylalanine requirement. Biochemical studies on extracts of strains carrying combinations of these aminotransferase mutations confirm the existence of two distinct enzymes with overlapping specificities for the alpha-keto acid analogues of tyrosine, phenylalanine, and aspartate. These enzymes can be distinguished by electrophoretic mobilities, by kinetic parameters using various substrates, and by a difference in tyrosine repressibility. In extracts of an ilvE- tyrB- aspC- triple mutant, no aminotransferase activity for the alpha-keto acids of tyrosine, phenylalanine, or aspartate could be detected.", "contents": "Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases. Two new mutations are described which, together, eliminate essentially all the aminotransferase activity required for de novo biosynthesis of tyrosine, phenylalanine, and aspartic acid in a K-12 strain of Escherichia coli. One mutation, designated tyrB, lies at about 80 min on the E. coli map and inactivates the \"tyrosine-repressible\" tyrosine/phenylalanine aminotransferase. The second mutation, aspC, maps at about 20 min and inactivates a nonrespressible aspartate aminotransferase that also has activity on the aromatic amino acids. In ilvE- strains, which lack the branched-chain amino acid aminotransferase, the presence of either the tyrosine-repressible aminotransferase or the aspartate aminotransferase is sufficient for growth in the absence of exogenous tyrosine, phenylalanine, or aspartate; the tyrosine-repressible enzyme is also active in leucine biosynthesis. The ilvE gene product alone can reverse a phenylalanine requirement. Biochemical studies on extracts of strains carrying combinations of these aminotransferase mutations confirm the existence of two distinct enzymes with overlapping specificities for the alpha-keto acid analogues of tyrosine, phenylalanine, and aspartate. These enzymes can be distinguished by electrophoretic mobilities, by kinetic parameters using various substrates, and by a difference in tyrosine repressibility. In extracts of an ilvE- tyrB- aspC- triple mutant, no aminotransferase activity for the alpha-keto acids of tyrosine, phenylalanine, or aspartate could be detected."}
{"id": "PMID:15984", "title": "Energy-dependent incorporation of sphingolipid precursors and fatty acids in Bacteriodes melaninogenicus.", "content": "Washed cells of Bacteroides melaninogenicus are unable to incorporate the sphingolipid precursor 3-ketodihydrosphingosine (3KDS) or dihydrosphingosine into the complete sphingolipids ceramide phosphorylethanolamine (CPE) and ceramide phosphorylglycerol (CPG), whereas growing cultures are able to do so. This result suggested that an energy source was required by washed cells to initiate the incorporation of 3KDS. Investigation of a number of energy sources for B. melaninogenicus showed that glutamine was active in driving the incorporation of 3KDS. This system shows saturation kinetics. Besides glutamine, only asparagine and reduced nicotinamide adenine dinucleotide (NADH) are effective; glutamate and other compounds are inactive. The glutamine-driven system is sensitive to 2,4-dinitrophenol, azide, N,N'- dicyclohexylcarbodiimide, and carbonyl cyanide m-chlorophenylhydrazone. Asparagine plus NADH shows a synergistic effect in stimulating the incorporation of 3KDS into CPE and CPG in washed cells. However, glutamine plus NADH and glutamine plus asparagine show no such synergy. The cytochrome-free mutant of B. melaninogenicus, strain S, incorporates 3KDS in a manner similar to the parent strain when glutamine is used to drive the reaction; NADH or asparagine, however, are ineffective when used with strain S. Vitamin K-depleted cells of B. melaninogenicus are similar to vitamin K-grown cells, when glutamine or NADH is used to drive the 3KDS incorporation. Glutamine and NADH are also effective in stimulating the incorporation of palmitate and acetate by washed cells of B, melaninogenicus. Increased incorporation of these fatty acids into CPE, CPG, 3KDS, and other phospholipids is significantly increased by the presence of glutamine or NADH. Thus, energization of the membrane of B. melaninogenicus by glutamine or the electron transport system by NADH or asparagine is required for sphingolipid and other phospholipid synthesis. The relationship of this energization to possible transport of sphingolipid precursors is discussed.", "contents": "Energy-dependent incorporation of sphingolipid precursors and fatty acids in Bacteriodes melaninogenicus. Washed cells of Bacteroides melaninogenicus are unable to incorporate the sphingolipid precursor 3-ketodihydrosphingosine (3KDS) or dihydrosphingosine into the complete sphingolipids ceramide phosphorylethanolamine (CPE) and ceramide phosphorylglycerol (CPG), whereas growing cultures are able to do so. This result suggested that an energy source was required by washed cells to initiate the incorporation of 3KDS. Investigation of a number of energy sources for B. melaninogenicus showed that glutamine was active in driving the incorporation of 3KDS. This system shows saturation kinetics. Besides glutamine, only asparagine and reduced nicotinamide adenine dinucleotide (NADH) are effective; glutamate and other compounds are inactive. The glutamine-driven system is sensitive to 2,4-dinitrophenol, azide, N,N'- dicyclohexylcarbodiimide, and carbonyl cyanide m-chlorophenylhydrazone. Asparagine plus NADH shows a synergistic effect in stimulating the incorporation of 3KDS into CPE and CPG in washed cells. However, glutamine plus NADH and glutamine plus asparagine show no such synergy. The cytochrome-free mutant of B. melaninogenicus, strain S, incorporates 3KDS in a manner similar to the parent strain when glutamine is used to drive the reaction; NADH or asparagine, however, are ineffective when used with strain S. Vitamin K-depleted cells of B. melaninogenicus are similar to vitamin K-grown cells, when glutamine or NADH is used to drive the 3KDS incorporation. Glutamine and NADH are also effective in stimulating the incorporation of palmitate and acetate by washed cells of B, melaninogenicus. Increased incorporation of these fatty acids into CPE, CPG, 3KDS, and other phospholipids is significantly increased by the presence of glutamine or NADH. Thus, energization of the membrane of B. melaninogenicus by glutamine or the electron transport system by NADH or asparagine is required for sphingolipid and other phospholipid synthesis. The relationship of this energization to possible transport of sphingolipid precursors is discussed."}
{"id": "PMID:15985", "title": "Regulation of galactose oxidase synthesis and secretion in Dactylium dendroides: effects of pH and culture density.", "content": "The effects of pH and growth density on the amount of an extracellular enzyme, galactose oxidase, synthesized by the fungus Dactylium dendroides were studied. Growth at a pH below 6.7 caused a decrease in the ability of the organism to release galactose oxidase. The enzyme retained by these fungal cells was liberated whenever the pH was raised to 7.0. Cycloheximide addition failed to inhibit the appearance of this protein; [3H]leucine added prior to pH adjustment was not incorporated into the released protein, These observations indicate the released protein is not newly synthesized protein. The retained enzyme would be secreted slowly over a 2-day period if the pH was not increased. In addition to regulating protein retention, pH was also shown to be associated with vacuolization, cell volume, culture density, and inhibition of protein synthesis. Cultures maintained at low pH were characterized by a dense growth consisting of highly vacuolated, buoyant, fungal hyphae. Increasing the pH from 6 to 7 caused a decrease in vacuole size. Cells grown at neutral pH maintained a lower density of growth and, based on activity measurements, synthesized 33% more galactose oxidase. Furthermore, cultures grown at pH 6.0 and maintained at a lower cell density produced galactose oxidase at a level similar to that of cells grown at neutral pH. Thus, the elevated density of the cell culture was inhibitory to galactose oxidase synthesis. The observed effects on protein synthesis and release were rather specific for galactose oxidase, since other extracellular proteins appeared in the earliest stages of growth.", "contents": "Regulation of galactose oxidase synthesis and secretion in Dactylium dendroides: effects of pH and culture density. The effects of pH and growth density on the amount of an extracellular enzyme, galactose oxidase, synthesized by the fungus Dactylium dendroides were studied. Growth at a pH below 6.7 caused a decrease in the ability of the organism to release galactose oxidase. The enzyme retained by these fungal cells was liberated whenever the pH was raised to 7.0. Cycloheximide addition failed to inhibit the appearance of this protein; [3H]leucine added prior to pH adjustment was not incorporated into the released protein, These observations indicate the released protein is not newly synthesized protein. The retained enzyme would be secreted slowly over a 2-day period if the pH was not increased. In addition to regulating protein retention, pH was also shown to be associated with vacuolization, cell volume, culture density, and inhibition of protein synthesis. Cultures maintained at low pH were characterized by a dense growth consisting of highly vacuolated, buoyant, fungal hyphae. Increasing the pH from 6 to 7 caused a decrease in vacuole size. Cells grown at neutral pH maintained a lower density of growth and, based on activity measurements, synthesized 33% more galactose oxidase. Furthermore, cultures grown at pH 6.0 and maintained at a lower cell density produced galactose oxidase at a level similar to that of cells grown at neutral pH. Thus, the elevated density of the cell culture was inhibitory to galactose oxidase synthesis. The observed effects on protein synthesis and release were rather specific for galactose oxidase, since other extracellular proteins appeared in the earliest stages of growth."}
{"id": "PMID:15986", "title": "Morphology of Ureaplasma urealyticum (T-mycoplasma) organisms and colonies.", "content": "The morphology of Ureaplasm urealyticum in broth cultures was studied by phase-contrast microscopy. Most organisms appeared singly or in pairs. Long filaments and long chains of cocci, common in classical mycoplasma cultures, were not observed. On solid medium, U. urealyticum produced \"fried-egg\" colonies which developed according to the scheme suggested by Razin and Oliver (J. Gen. Microbiol., 1961) for the morphogenesis of the classical mycoplasma colonies. The formation of the peripheral zone of the colonies followed that of the central zone only when growth conditions were adequate, Hence, the appearance of peripheral zones, and consequently the larger colony size, can be taken as an indicator of improved growth conditions. Incubation in an atmosphere of 100% CO2 resulted in significantly larger colonies than in an atmosphere of N2, O2, or air. CO2 acts as a buffer, keeping the pH at the optimal range for Ureaplasma growth (pH 6.0 to 6.5) in the presence of the ammonia produced from the urea hydrolyzed by the organisms. The addition to the medium of 0.01 M urea together with 0.01 M putrescine enabled better growth than with urea alone. Small amounts of phosphate improved growth in an atmosphere of CO2, apparently fulfilling a nutritional role. Under nitrogen, higher phosphate concentrations were required for good growth, apparently serving as a buffer as well as a nutrient. Sodium chloride and sucrose which had been added to increase the tonicity of the medium inhibited growth above 0.1 M. An increase in the agar concentration above 2% resulted in decreased colony size. Likewise, prolonged drying of the agar plates caused a marked decrease in colony size, mostly affecting the peripheral zone. The addition of both urea and putrescine to the growth medium and incubation in a humidified CO2 atmosphere are recommended for improved growth and formation of fried-egg colonies of U. ureaplyticum on agar. It must be emphasized that these experiments were carried out with a laboratory-adapted strain.", "contents": "Morphology of Ureaplasma urealyticum (T-mycoplasma) organisms and colonies. The morphology of Ureaplasm urealyticum in broth cultures was studied by phase-contrast microscopy. Most organisms appeared singly or in pairs. Long filaments and long chains of cocci, common in classical mycoplasma cultures, were not observed. On solid medium, U. urealyticum produced \"fried-egg\" colonies which developed according to the scheme suggested by Razin and Oliver (J. Gen. Microbiol., 1961) for the morphogenesis of the classical mycoplasma colonies. The formation of the peripheral zone of the colonies followed that of the central zone only when growth conditions were adequate, Hence, the appearance of peripheral zones, and consequently the larger colony size, can be taken as an indicator of improved growth conditions. Incubation in an atmosphere of 100% CO2 resulted in significantly larger colonies than in an atmosphere of N2, O2, or air. CO2 acts as a buffer, keeping the pH at the optimal range for Ureaplasma growth (pH 6.0 to 6.5) in the presence of the ammonia produced from the urea hydrolyzed by the organisms. The addition to the medium of 0.01 M urea together with 0.01 M putrescine enabled better growth than with urea alone. Small amounts of phosphate improved growth in an atmosphere of CO2, apparently fulfilling a nutritional role. Under nitrogen, higher phosphate concentrations were required for good growth, apparently serving as a buffer as well as a nutrient. Sodium chloride and sucrose which had been added to increase the tonicity of the medium inhibited growth above 0.1 M. An increase in the agar concentration above 2% resulted in decreased colony size. Likewise, prolonged drying of the agar plates caused a marked decrease in colony size, mostly affecting the peripheral zone. The addition of both urea and putrescine to the growth medium and incubation in a humidified CO2 atmosphere are recommended for improved growth and formation of fried-egg colonies of U. ureaplyticum on agar. It must be emphasized that these experiments were carried out with a laboratory-adapted strain."}
{"id": "PMID:15987", "title": "Extracellular acid protease of Aspergillus oryzae grown on liquid media: multiple forms due to association with heterogeneous polysaccharides.", "content": "The acid protease (EC 2.4.23.6) that is produced extracellularly when Aspergillus oryzae is grown on liquid media has been isolated and characterized. The enzyme was purified by precipitation with tannic acid, chromatography on Duolite A-2, and gel filtration on Sephadex G-100. The last step yielded four active components, with varying molecular weights ranging from 42,000 to 60,000. Two of them, designated E1 and E1a, with molecular weights of 60,000 and 55,000, respectively, were heterogeneous on isoelectric focusing, both giving at least three enzyme species with different isoelectric points, whereas the other two, E1b and E2, with molecular weights of 49,000 and 42,000, respectively, were essentially homogeneous. These four enzymes activated bovine pancreatic trypsinogen and had the same pH optima in the acid pH range. They had essentially the same amino acid composition and immunologically cross-reacted with each other. These catalytic, chemical, and immunological properties are similar to those of acid protease A1 and A2 from A. oryzae grown on solid bran media. Unlike acid protease from solid bran culture, which contains both carbohydrate-containing and the carbohydrate-free species, all of the four enzymes, E1, E1a, E1b, and E2, contained carbohydrate, ranging from 18.9 to 43% and comprising three hexoses, glucose, galactose, and mannose. The carbohydrate portions were polysaccharide in nature and heterogeneous with respect to both molecular weight and sugar composition, and at least a part of the carbohydrate was present in the form of homopolysaccharides such as galactan and mannan. These findings indicate that polysaccharide chains with different molecular weights and with different chemical compositions are apparently responsible for the microheterogeneity of acid protease.", "contents": "Extracellular acid protease of Aspergillus oryzae grown on liquid media: multiple forms due to association with heterogeneous polysaccharides. The acid protease (EC 2.4.23.6) that is produced extracellularly when Aspergillus oryzae is grown on liquid media has been isolated and characterized. The enzyme was purified by precipitation with tannic acid, chromatography on Duolite A-2, and gel filtration on Sephadex G-100. The last step yielded four active components, with varying molecular weights ranging from 42,000 to 60,000. Two of them, designated E1 and E1a, with molecular weights of 60,000 and 55,000, respectively, were heterogeneous on isoelectric focusing, both giving at least three enzyme species with different isoelectric points, whereas the other two, E1b and E2, with molecular weights of 49,000 and 42,000, respectively, were essentially homogeneous. These four enzymes activated bovine pancreatic trypsinogen and had the same pH optima in the acid pH range. They had essentially the same amino acid composition and immunologically cross-reacted with each other. These catalytic, chemical, and immunological properties are similar to those of acid protease A1 and A2 from A. oryzae grown on solid bran media. Unlike acid protease from solid bran culture, which contains both carbohydrate-containing and the carbohydrate-free species, all of the four enzymes, E1, E1a, E1b, and E2, contained carbohydrate, ranging from 18.9 to 43% and comprising three hexoses, glucose, galactose, and mannose. The carbohydrate portions were polysaccharide in nature and heterogeneous with respect to both molecular weight and sugar composition, and at least a part of the carbohydrate was present in the form of homopolysaccharides such as galactan and mannan. These findings indicate that polysaccharide chains with different molecular weights and with different chemical compositions are apparently responsible for the microheterogeneity of acid protease."}
{"id": "PMID:15988", "title": "Choline metabolism in pneumococci.", "content": "Phosphorylcholine and cytidine diphosphocholine as well as two enzyme activities, a choline kinase and a cytidine diphosphocholine pyrophosphorylase, were identified in pneumococcal extracts. It is suggested that cytidine diphosphocholine may be a biosynthetic precursor of the choline moiety in the teichoic acids of pneumococcus.", "contents": "Choline metabolism in pneumococci. Phosphorylcholine and cytidine diphosphocholine as well as two enzyme activities, a choline kinase and a cytidine diphosphocholine pyrophosphorylase, were identified in pneumococcal extracts. It is suggested that cytidine diphosphocholine may be a biosynthetic precursor of the choline moiety in the teichoic acids of pneumococcus."}
{"id": "PMID:15989", "title": "O-alkylhomoserine synthesis catalyzed by O-acetylhomoserine sulfhydrylase in microorganisms.", "content": "An enzyme that can synthesize O-alkylhomoserine from alcohols and O-acetylhomoserine was purified from Corynebacterium acetophilum. The enzyme was found to be identical to O-acetylhomoserine sulfhydrylase; a preparation that appeared homogeneous on polyacrylamide gel electrophoresis showed both O-alkylhomoserine-synthesizing and O-acetylhomoserine sulfhydrylase activities. Its molecular weight was determined to be about 220,000, and it consisted of two subunits. Its pH and temperature optima for the two reactions were the same. Besides catalyzing the formation of homocysteine from O-acetylhomoserine and sulfide, it also catalyzed the syntheses of O-alkylhomoserines corresponding to the alcohols added form O-acetylhomoserine and ethyl alcohol, n-propylalcohol, n-butyl alcohol, methyl alcohol, and n-pentyl alcohol, its activities with these alcohols decreasing in that order. L-Homoserine, O-succinylhomoserine, and O-acetylserine reacted with sulfide. O-ethylhomoserine, O-acetylthreonine, O-succinylhomoserine, and O-acetylserine inhibited both enzyme activities. O-acetylhomoserine sulfhydrylase purified from Saccharomyces cerevisiae also showed O-alkylhomoserine-synthesizing activity. Thus, O-acetylhomoserine sulfhydrylase seems to catalyze O-alkylhomoserine synthesis in the presence of appropriate concentrations of alcohol and O-acetylhomoserine in microorganisms.", "contents": "O-alkylhomoserine synthesis catalyzed by O-acetylhomoserine sulfhydrylase in microorganisms. An enzyme that can synthesize O-alkylhomoserine from alcohols and O-acetylhomoserine was purified from Corynebacterium acetophilum. The enzyme was found to be identical to O-acetylhomoserine sulfhydrylase; a preparation that appeared homogeneous on polyacrylamide gel electrophoresis showed both O-alkylhomoserine-synthesizing and O-acetylhomoserine sulfhydrylase activities. Its molecular weight was determined to be about 220,000, and it consisted of two subunits. Its pH and temperature optima for the two reactions were the same. Besides catalyzing the formation of homocysteine from O-acetylhomoserine and sulfide, it also catalyzed the syntheses of O-alkylhomoserines corresponding to the alcohols added form O-acetylhomoserine and ethyl alcohol, n-propylalcohol, n-butyl alcohol, methyl alcohol, and n-pentyl alcohol, its activities with these alcohols decreasing in that order. L-Homoserine, O-succinylhomoserine, and O-acetylserine reacted with sulfide. O-ethylhomoserine, O-acetylthreonine, O-succinylhomoserine, and O-acetylserine inhibited both enzyme activities. O-acetylhomoserine sulfhydrylase purified from Saccharomyces cerevisiae also showed O-alkylhomoserine-synthesizing activity. Thus, O-acetylhomoserine sulfhydrylase seems to catalyze O-alkylhomoserine synthesis in the presence of appropriate concentrations of alcohol and O-acetylhomoserine in microorganisms."}
{"id": "PMID:15990", "title": "Alkaline structural transition of 4-nitrobenz-2-oxa-1,3-diazolyl-Lysozyme. Kinetic and spectroscopic investigations.", "content": "When lysozyme is reacted with 4-chloro-7-nitrobenz-2-oxa-1,3-diazole (NBD-CL), A 1:1 covalent product is produced, in which the NBD group arylates the phenolic hydroxyl group of Tyr-23 (Aboderin, A. A., and Boedefeld, E. (1976) Biochim. Biophys. Acta 420, 177). Changing the pH from neutral to alkaline conditions results in a large spectral shift of the absorption band associated with the NBD chromophore (Aboderin, A. A., Boedefeld, E., and Luisi, P. L. (1973) Biochim. Biophys. Acta 328, 30). In the present work it is shown that this spectral change is due to the formation of a sigma complex in which a hydroxyl ion is added to the aromatic nucleus of the nitrobenzoxadiazole system. Circular dichroic studies suggest that the NBD group is held in a conformationally rigid state in the protein. The kinetics of the spectral change accompanying the formation of the sigma complex has been investigated with a rapid mixing stopped flow spectrophotometer both in the modified enzyme and in the low molecular weight model compounds N-acetyl-(O-NBD)-L-tyrosinamide and glycyl-(O-NBD)-L-tyrosine. In the pH range from 10.1 to 12.7, the time course of the reaction is first order in the case of the modified enzyme (k = 4.8 s-1) and bimolecular and much slower (under pseudo-first order conditions) in the low molecular weight compounds. It is suggested that in the enzyme the reaction proceeds much faster because of the hydrophobic environment around the reacting groups. It is further suggested that the unimolecularity in the enzyme is due to a rate-determining isomerization step, probably connected with a local rearrangement of the protein conformation following the ionization of Tyr-20.", "contents": "Alkaline structural transition of 4-nitrobenz-2-oxa-1,3-diazolyl-Lysozyme. Kinetic and spectroscopic investigations. When lysozyme is reacted with 4-chloro-7-nitrobenz-2-oxa-1,3-diazole (NBD-CL), A 1:1 covalent product is produced, in which the NBD group arylates the phenolic hydroxyl group of Tyr-23 (Aboderin, A. A., and Boedefeld, E. (1976) Biochim. Biophys. Acta 420, 177). Changing the pH from neutral to alkaline conditions results in a large spectral shift of the absorption band associated with the NBD chromophore (Aboderin, A. A., Boedefeld, E., and Luisi, P. L. (1973) Biochim. Biophys. Acta 328, 30). In the present work it is shown that this spectral change is due to the formation of a sigma complex in which a hydroxyl ion is added to the aromatic nucleus of the nitrobenzoxadiazole system. Circular dichroic studies suggest that the NBD group is held in a conformationally rigid state in the protein. The kinetics of the spectral change accompanying the formation of the sigma complex has been investigated with a rapid mixing stopped flow spectrophotometer both in the modified enzyme and in the low molecular weight model compounds N-acetyl-(O-NBD)-L-tyrosinamide and glycyl-(O-NBD)-L-tyrosine. In the pH range from 10.1 to 12.7, the time course of the reaction is first order in the case of the modified enzyme (k = 4.8 s-1) and bimolecular and much slower (under pseudo-first order conditions) in the low molecular weight compounds. It is suggested that in the enzyme the reaction proceeds much faster because of the hydrophobic environment around the reacting groups. It is further suggested that the unimolecularity in the enzyme is due to a rate-determining isomerization step, probably connected with a local rearrangement of the protein conformation following the ionization of Tyr-20."}
{"id": "PMID:15991", "title": "Resolution and partial characterization of two aldehyde reductases of mammalian liver.", "content": "Investigation of NADP-dependent aldehyde reductase activity in mouse liver led to the finding that two distinct reductases are separable by DE52 ion exchange chromatography. Aldehyde reductase I (AR I) appears in the effluent, while aldehyde reductase II (AR II) is eluted with a salt gradient. By several procedures AR II was purified over 1100-fold from liver supernatant fraction, but AR I could be pruified only 107-fold because of its instability. The two enzymes are different in regard to pH optimum, substrate specificity, response to inhibitors, and reactivity with antibody to AR II. While both enzymes utilize aromatic aldehydes well, only AR II ACTS ON D-glucuronate, indicating that it is the aldyhyde reductase recently reported to be identical to NADP-L-gulonate dehydrogenase. The presence of two NADP-linked aldehyde reductases in liver has apparently not heretofore been reported.", "contents": "Resolution and partial characterization of two aldehyde reductases of mammalian liver. Investigation of NADP-dependent aldehyde reductase activity in mouse liver led to the finding that two distinct reductases are separable by DE52 ion exchange chromatography. Aldehyde reductase I (AR I) appears in the effluent, while aldehyde reductase II (AR II) is eluted with a salt gradient. By several procedures AR II was purified over 1100-fold from liver supernatant fraction, but AR I could be pruified only 107-fold because of its instability. The two enzymes are different in regard to pH optimum, substrate specificity, response to inhibitors, and reactivity with antibody to AR II. While both enzymes utilize aromatic aldehydes well, only AR II ACTS ON D-glucuronate, indicating that it is the aldyhyde reductase recently reported to be identical to NADP-L-gulonate dehydrogenase. The presence of two NADP-linked aldehyde reductases in liver has apparently not heretofore been reported."}
{"id": "PMID:15992", "title": "gamma-Glutamylcysteine synthetase. Further purification, \"half of the sites\" reactivity, subunits, and specificity.", "content": "gamma-Glutamylcysteine synthetase was purified from rat liver by an improved method involving chromatography on Sepharose-aminohexyl-ATP to a specific activity of about 1600 units/mg, or approximately twice that previously obtained; it is thus the most active preparation of this enzyme thus far isolated. The earlier preparation, which is homogeneous on polyacrylamide gel electrophoresis, exhibits \"half of the sites\" reactivity in that it binds a maximum of 0.5 mol of the inhibitor L-methionine-S-sulfoximine phosphate per mol of enzyme. In contrast, the present enzyme preparation binds 1 mol of methionine sulfoximine phosphate per mol of enzyme; it also differs from the enzyme obtained earlier in exhibiting much less ATPase activity and less activity in catalyzing ATP-dependent cyclization of glutamate. gamma-Glutamylcysteine synthetase dissociates in sodium dodecyl sulfate into two nonidentical subunits of apparent molecular weights 74,000 and 24,000; after cross-linking with dimethyl-suberimidate, a species having a molecular weight of about 100,000 was found on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. New information has been obtained about the interaction of the enzyme with glutamate analogs; thus, the enzyme is active with such glutamate analogs as beta-glutamate, N-methyl-L-glutamate, and threo-beta-hydroxy-L-glutanate, and it is effectively inhibited by cis-1-amino-1,3-dicarboxycyclonexane, 2-amino-4-phosphonobutyrate, and gamma-methylglutamate.", "contents": "gamma-Glutamylcysteine synthetase. Further purification, \"half of the sites\" reactivity, subunits, and specificity. gamma-Glutamylcysteine synthetase was purified from rat liver by an improved method involving chromatography on Sepharose-aminohexyl-ATP to a specific activity of about 1600 units/mg, or approximately twice that previously obtained; it is thus the most active preparation of this enzyme thus far isolated. The earlier preparation, which is homogeneous on polyacrylamide gel electrophoresis, exhibits \"half of the sites\" reactivity in that it binds a maximum of 0.5 mol of the inhibitor L-methionine-S-sulfoximine phosphate per mol of enzyme. In contrast, the present enzyme preparation binds 1 mol of methionine sulfoximine phosphate per mol of enzyme; it also differs from the enzyme obtained earlier in exhibiting much less ATPase activity and less activity in catalyzing ATP-dependent cyclization of glutamate. gamma-Glutamylcysteine synthetase dissociates in sodium dodecyl sulfate into two nonidentical subunits of apparent molecular weights 74,000 and 24,000; after cross-linking with dimethyl-suberimidate, a species having a molecular weight of about 100,000 was found on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. New information has been obtained about the interaction of the enzyme with glutamate analogs; thus, the enzyme is active with such glutamate analogs as beta-glutamate, N-methyl-L-glutamate, and threo-beta-hydroxy-L-glutanate, and it is effectively inhibited by cis-1-amino-1,3-dicarboxycyclonexane, 2-amino-4-phosphonobutyrate, and gamma-methylglutamate."}
{"id": "PMID:15993", "title": "Covalent interaction of L-2-amino-4-oxo-5-chloropentanoate at glutamate binding site of gamma-glutamylcysteine synthetase.", "content": "gamma-Glutamylcysteine synthetase is inactivated by incubation with low concentrations of L-2-amino-4-oxo-5-chloropentanoate. Very low concentrations of magnesium ions or certain other divalent cations are required for inactivation. L-Glutamate, but not D-glutamate or L-glutamine, protected against inactivation and the protective effect of L-glutamate was increased in the presence of ATP or ADP. L-alpha-Aminobutyrate increased the rate of inactivation by the chloroketone. When the chloroketone was added to the dipeptide synthesis system, inhibition was competitive with L-glutamate. Iodoacetamide also inhibited the enzyme; however, this reagent is much less effective than the chloroketone and inhibition by iodoacetamide is less effectively prevented by L-glutamate. Studies with 14C-labeled chloroketone showed that this reagent binds stoichiometrically to the enzyme, and that it binds exclusively to its heavy subunit.", "contents": "Covalent interaction of L-2-amino-4-oxo-5-chloropentanoate at glutamate binding site of gamma-glutamylcysteine synthetase. gamma-Glutamylcysteine synthetase is inactivated by incubation with low concentrations of L-2-amino-4-oxo-5-chloropentanoate. Very low concentrations of magnesium ions or certain other divalent cations are required for inactivation. L-Glutamate, but not D-glutamate or L-glutamine, protected against inactivation and the protective effect of L-glutamate was increased in the presence of ATP or ADP. L-alpha-Aminobutyrate increased the rate of inactivation by the chloroketone. When the chloroketone was added to the dipeptide synthesis system, inhibition was competitive with L-glutamate. Iodoacetamide also inhibited the enzyme; however, this reagent is much less effective than the chloroketone and inhibition by iodoacetamide is less effectively prevented by L-glutamate. Studies with 14C-labeled chloroketone showed that this reagent binds stoichiometrically to the enzyme, and that it binds exclusively to its heavy subunit."}
{"id": "PMID:15994", "title": "Isolation, crystallization, and properties of indolyl-3-alkane alpha-hydroxylase. A novel tryptophan-metabolizing enzyme.", "content": "Indolyl-3-alkane alpha-hydroxylase, a novel tryptophan-metabolizing enzyme, was prepared in crystalline form from soil isolate organism Pseudomonas XA. Emission spectroscopy and atomic absorption analyses of purified enzyme revealed the presence of iron (0.8 mol/mol of protein), and a number of observations supported the presence of heme prosthetic group (1.1 mol/mol of protein). The S20,w value of indolyl-3-alkane alpha-hydroxylase is 10.2 S, and the molecular weight by sedimentation equilibrium ultracentrifugation is 250,000. The E1%280 of the enzyme is 21, and the isoelectric point by isoelectric focusing on ampholine polyacrylamide gel plates is 4.8. The enzyme catalyzes hydroxylation on the side chain of a variety of 3-substituted indole compounds, including certain tryptophan-containing oligopeptides. The reaction product from tryptamine was identified by proton nuclear magnetic resonance and gas chromatography/mass spectroscopy analyses. While the indole ring remained intact, hydroxylation occurred at the side chain carbon adjacent to the ring. Nuclear magnetic resonance studies indicated that hydroxylation always took place at the same position when the substrate was tryptophan methyl ester, tryptophol, indole-3-propionate, or indole-3-butyrate. No other chemical change occurred when these substrates were incubated with the enzyme. The Km value of indolyl-3-alkane alpha-hydroxylase for L-tryptophan is 2.4 X 10(-6) M, at pH 7.2. The enzyme is inhibited by potassium cyanide (0.1 mM) or hydroxylamine (1mM), but not by NaBH4 (25 mM), aminooxyacetic acid (7mM), quinacrine (1 mM), chlortetracycline (1 mM), p-mercuribenzoate (0.1 mM), or ethylenediaminetetraacetate (1 mM). The plasma half-life (t1/2) of indolyl-3-alkane alpha-hydroxylase in tumor-bearing mice is approximately 25 h.", "contents": "Isolation, crystallization, and properties of indolyl-3-alkane alpha-hydroxylase. A novel tryptophan-metabolizing enzyme. Indolyl-3-alkane alpha-hydroxylase, a novel tryptophan-metabolizing enzyme, was prepared in crystalline form from soil isolate organism Pseudomonas XA. Emission spectroscopy and atomic absorption analyses of purified enzyme revealed the presence of iron (0.8 mol/mol of protein), and a number of observations supported the presence of heme prosthetic group (1.1 mol/mol of protein). The S20,w value of indolyl-3-alkane alpha-hydroxylase is 10.2 S, and the molecular weight by sedimentation equilibrium ultracentrifugation is 250,000. The E1%280 of the enzyme is 21, and the isoelectric point by isoelectric focusing on ampholine polyacrylamide gel plates is 4.8. The enzyme catalyzes hydroxylation on the side chain of a variety of 3-substituted indole compounds, including certain tryptophan-containing oligopeptides. The reaction product from tryptamine was identified by proton nuclear magnetic resonance and gas chromatography/mass spectroscopy analyses. While the indole ring remained intact, hydroxylation occurred at the side chain carbon adjacent to the ring. Nuclear magnetic resonance studies indicated that hydroxylation always took place at the same position when the substrate was tryptophan methyl ester, tryptophol, indole-3-propionate, or indole-3-butyrate. No other chemical change occurred when these substrates were incubated with the enzyme. The Km value of indolyl-3-alkane alpha-hydroxylase for L-tryptophan is 2.4 X 10(-6) M, at pH 7.2. The enzyme is inhibited by potassium cyanide (0.1 mM) or hydroxylamine (1mM), but not by NaBH4 (25 mM), aminooxyacetic acid (7mM), quinacrine (1 mM), chlortetracycline (1 mM), p-mercuribenzoate (0.1 mM), or ethylenediaminetetraacetate (1 mM). The plasma half-life (t1/2) of indolyl-3-alkane alpha-hydroxylase in tumor-bearing mice is approximately 25 h."}
{"id": "PMID:15995", "title": "Crystalline hemoprotein from Pseudomonas that catalyzes oxidation of side chain of tryptophan and other indole derivatives.", "content": "A new enzyme which catalyzes the oxidation of the side chain of tryptophan and other indole derivatives, has been purified to apparent homogeneity from Pseudomonas and crystallized. The overall purification was about 25-fold with a yield of 4.5%. The purified enzyme was apparently homogeneous as judged by polyacrylamide gel electrophoresis. The molecular weight estimated by gel filtration was approximately 280,000 and sedimentation coefficient (S20,w) was 11 by sucrose density gradient ultracentrifugation. The absorption spectra indicated that the enzyme was a hemoprotein. The purified enzyme was shown to catalyze the reaction in which 1 mol each of NH3 and CO2 was formed at the expense of 1 mol each of L-tryptophan and molecular oxygen. Neither peroxidase nor catalase activity was detected in the purified enzyme and no formation of H2O2 was observed during the enzyme reaction. The product(s) of the reaction was unstable but was converted to and was identified as its stable quinoxaline derivative, 2-(3-indolyl)quinoxaline, in the presence of o-phenylenediamine. These results indicate that the product of the reaction was 3-indolylglycoaldehyde or 3-indolylglyoxal. A variety of other indole derivatives such as D-tryptophan, 5-hydroxyl-L-tryptophan, tryptamine, serotonin, melatonin, N-acetyl-L-tryptophan, N-acetyl-L-tryptophanamide, 3-indoleacetamide, 3-indolelactic acid, 3-indolepropionic acid, 3-indoleethanol, and skatole were also substrates.", "contents": "Crystalline hemoprotein from Pseudomonas that catalyzes oxidation of side chain of tryptophan and other indole derivatives. A new enzyme which catalyzes the oxidation of the side chain of tryptophan and other indole derivatives, has been purified to apparent homogeneity from Pseudomonas and crystallized. The overall purification was about 25-fold with a yield of 4.5%. The purified enzyme was apparently homogeneous as judged by polyacrylamide gel electrophoresis. The molecular weight estimated by gel filtration was approximately 280,000 and sedimentation coefficient (S20,w) was 11 by sucrose density gradient ultracentrifugation. The absorption spectra indicated that the enzyme was a hemoprotein. The purified enzyme was shown to catalyze the reaction in which 1 mol each of NH3 and CO2 was formed at the expense of 1 mol each of L-tryptophan and molecular oxygen. Neither peroxidase nor catalase activity was detected in the purified enzyme and no formation of H2O2 was observed during the enzyme reaction. The product(s) of the reaction was unstable but was converted to and was identified as its stable quinoxaline derivative, 2-(3-indolyl)quinoxaline, in the presence of o-phenylenediamine. These results indicate that the product of the reaction was 3-indolylglycoaldehyde or 3-indolylglyoxal. A variety of other indole derivatives such as D-tryptophan, 5-hydroxyl-L-tryptophan, tryptamine, serotonin, melatonin, N-acetyl-L-tryptophan, N-acetyl-L-tryptophanamide, 3-indoleacetamide, 3-indolelactic acid, 3-indolepropionic acid, 3-indoleethanol, and skatole were also substrates."}
{"id": "PMID:15996", "title": "Enzymatic conversion of bilirubin monoglucuronide to diglucuronide by rat liver plasma membranes.", "content": "Formation of bilirubin monoglucuronide from unconjugated bilirubin requires a microsomal enzyme, UDP-glucuronate glucuronyltransferase (EC 2.4.1.17). Conversion of bilirubin monoglucuronide to bilirubin diglucuronide, the major bilirubin conjugate in bile, was studied in subcellular fractions of rat liver. The highest specific activity for bilirubin diglucuronide formation occurred in a fraction highly enriched in plasma membranes. Studies of reaction stoichiometry and utilization of UDP-D-[14C]glucuronic acid revealed that conversion of bilirubin monoglucuronide to bilirubin diglucuronide is not catalyzed by UDP-glucuronyltransferase, and results from transglucuronidation of bilirubin monoglucuronide, with formation of bilirubin diglucuronide and unconjugated bilirubin. When unconjugated bilirubin was infused intravenously into rats at rates exceeding the maximal hepatic excretory capacity, bilirubin monoglucuronide accumulated in serum and bilirubin diglucuronide was found exclusively in bile as the predominant bilirubin metabolite. These results suggest that formation of bilirubin diglucuronide occurs at the surface membrane of the liver cell. Conversion of bilirubin monoglucuronide to bilirubin diglucuronide may play a role in the transport of bilirubin glucuronides from liver to bile.", "contents": "Enzymatic conversion of bilirubin monoglucuronide to diglucuronide by rat liver plasma membranes. Formation of bilirubin monoglucuronide from unconjugated bilirubin requires a microsomal enzyme, UDP-glucuronate glucuronyltransferase (EC 2.4.1.17). Conversion of bilirubin monoglucuronide to bilirubin diglucuronide, the major bilirubin conjugate in bile, was studied in subcellular fractions of rat liver. The highest specific activity for bilirubin diglucuronide formation occurred in a fraction highly enriched in plasma membranes. Studies of reaction stoichiometry and utilization of UDP-D-[14C]glucuronic acid revealed that conversion of bilirubin monoglucuronide to bilirubin diglucuronide is not catalyzed by UDP-glucuronyltransferase, and results from transglucuronidation of bilirubin monoglucuronide, with formation of bilirubin diglucuronide and unconjugated bilirubin. When unconjugated bilirubin was infused intravenously into rats at rates exceeding the maximal hepatic excretory capacity, bilirubin monoglucuronide accumulated in serum and bilirubin diglucuronide was found exclusively in bile as the predominant bilirubin metabolite. These results suggest that formation of bilirubin diglucuronide occurs at the surface membrane of the liver cell. Conversion of bilirubin monoglucuronide to bilirubin diglucuronide may play a role in the transport of bilirubin glucuronides from liver to bile."}
{"id": "PMID:15997", "title": "Effect of concanavalin A on tyrosine aminotransferase in rat hepatoma tissue culture cells. Rapid reversible inactivation of soluble enzyme.", "content": "Concanavalin A added to intact cells at 37 degrees caused rapid and reversible inactivation of a soluble enzyme, tyrosine aminotransferase, in two lines of rat hepatoma tissue culture cells grown in monolayer culture. This temperature-dependent process was independent of de novo protein and RNA synthesis and independent of increased uptake of Ca2+ and Mg2+ or glucose. The inactivation could be reversed by adding alpha-methyl-D-mannopyranoside a competing sugar for concanavalin A binding. Other lectins known to bind to different sugars did not bring about the inactivation of tyrosine aminotransferase. Addition of concanavalin A did not result in the inactivation of another soluble enzyme, lactic dehydrogenase. The maintenance of tyrosine aminotransferase in an inactive form after the binding of concanavalin A to the cells required the continued presence of concanavalin A. This effect of concanavalin A could not be mimicked either by dibutyryl cyclic adenosine or guanosine monophosphoric acid. Incubation of cell extracts with concanavalin A did not result in inactivation nor did mixing of extracts from concanavalin A-treated cells with extracts from untreated cells. On the basis of these results we conclude that the following are the essential requirements for concanavalin A to bring about the inactivation of tyrosine aminotransferase: (a) the binding of native concanavalin A to the cells; (b) integrity of certain structural elements of the cells.", "contents": "Effect of concanavalin A on tyrosine aminotransferase in rat hepatoma tissue culture cells. Rapid reversible inactivation of soluble enzyme. Concanavalin A added to intact cells at 37 degrees caused rapid and reversible inactivation of a soluble enzyme, tyrosine aminotransferase, in two lines of rat hepatoma tissue culture cells grown in monolayer culture. This temperature-dependent process was independent of de novo protein and RNA synthesis and independent of increased uptake of Ca2+ and Mg2+ or glucose. The inactivation could be reversed by adding alpha-methyl-D-mannopyranoside a competing sugar for concanavalin A binding. Other lectins known to bind to different sugars did not bring about the inactivation of tyrosine aminotransferase. Addition of concanavalin A did not result in the inactivation of another soluble enzyme, lactic dehydrogenase. The maintenance of tyrosine aminotransferase in an inactive form after the binding of concanavalin A to the cells required the continued presence of concanavalin A. This effect of concanavalin A could not be mimicked either by dibutyryl cyclic adenosine or guanosine monophosphoric acid. Incubation of cell extracts with concanavalin A did not result in inactivation nor did mixing of extracts from concanavalin A-treated cells with extracts from untreated cells. On the basis of these results we conclude that the following are the essential requirements for concanavalin A to bring about the inactivation of tyrosine aminotransferase: (a) the binding of native concanavalin A to the cells; (b) integrity of certain structural elements of the cells."}
{"id": "PMID:15998", "title": "Selective association of spectrin with the cytoplasmic surface of human erythrocyte plasma membranes. Quantitative determination with purified (32P)spectrin.", "content": "A specific association between spectrin and the inner surface of the human erythrocyte membrane has been examined by measuring the binding of purified [32P]spectrin to inside out, spectrin-depleted vesicles and to right side out ghost vesicles. Spectrin was labeled by incubating erythrocytes with 32Pi, and eluted from the ghost membranes by extraction in 0.3 mM NaPO4, pH 7.6. [32P]Spectrin was separated from actin and other proteins and isolated in a nonaggregated state as a So20,w = 7 S (in 0.3 mM NaPO4) or So20,w = 8 S (in 20 mM KCl, 0.3 mM NaPO4) protein after sedimentation on linear sucrose gradients. Binding of [32P]spectrin to inverted vesicles devoid of spectrin and actin was at least 10-fold greater than to right side out membranes, and exhibited different properties. Association with inside out vesicles was slow, was decreased to the value for right side out vesicles at high pH, or after heating spectrin above 50 degrees prior to assay, and was saturable with increasing levels of spectrin. Binding to everted vesicles was rapid, unaffected by pH or by heating spectrin, and rose linearly with the concentration of spectrin. Scatchard plots of binding to inverted vesicles were linear at pH 7.6, with a KD of 45 microng/ml, while at pH 6.6, plots were curvilinear and consistent with two types of interactions with a KD of 4 and 19 microng/ml, respectively. The maximal binding capacity at both pH values was about 200 microng of spectrin/mg of membrane protein. Unlabeled spectrin competed for binding with 50% displacement at 27 microng/ml. [32P]Spectrin dissociated and associated with inverted vesicles with an identical dependence on ionic strength as observed for elution of native spectrin from ghosts. MgCl2, CaCl2 (1 to 4 mM) and EDTA (0.5 to 1 mM) had little effect on binding in the presence of 20 mM KCl, while at low ionic strength, MgCl2 (1 mM) increased binding and inhibited dissociation to the same extent as 10 to 20 mM KCl. Binding was abolished by pretreatment of vesicles with 0.1 M acetic acid, or with 0.1 microng/ml of trypsin. The periodic acid-Schiff-staining bands were unaffected by trypsin digestion which destroyed binding; mild digestion, which decreased binding only 50%, converted Band 3 almost completely to a membrane-bound 50,000-dalton fragment resistant to further proteolysis. These experiments suggest that attachment of spectrin to the cytoplasmic surface of the membrane results from a selective protein-protein interaction which is independent of erythrocyte actin. A direct role of the major sialoglycoprotein or Band 3 as a membrane binding site appears unlikely.", "contents": "Selective association of spectrin with the cytoplasmic surface of human erythrocyte plasma membranes. Quantitative determination with purified (32P)spectrin. A specific association between spectrin and the inner surface of the human erythrocyte membrane has been examined by measuring the binding of purified [32P]spectrin to inside out, spectrin-depleted vesicles and to right side out ghost vesicles. Spectrin was labeled by incubating erythrocytes with 32Pi, and eluted from the ghost membranes by extraction in 0.3 mM NaPO4, pH 7.6. [32P]Spectrin was separated from actin and other proteins and isolated in a nonaggregated state as a So20,w = 7 S (in 0.3 mM NaPO4) or So20,w = 8 S (in 20 mM KCl, 0.3 mM NaPO4) protein after sedimentation on linear sucrose gradients. Binding of [32P]spectrin to inverted vesicles devoid of spectrin and actin was at least 10-fold greater than to right side out membranes, and exhibited different properties. Association with inside out vesicles was slow, was decreased to the value for right side out vesicles at high pH, or after heating spectrin above 50 degrees prior to assay, and was saturable with increasing levels of spectrin. Binding to everted vesicles was rapid, unaffected by pH or by heating spectrin, and rose linearly with the concentration of spectrin. Scatchard plots of binding to inverted vesicles were linear at pH 7.6, with a KD of 45 microng/ml, while at pH 6.6, plots were curvilinear and consistent with two types of interactions with a KD of 4 and 19 microng/ml, respectively. The maximal binding capacity at both pH values was about 200 microng of spectrin/mg of membrane protein. Unlabeled spectrin competed for binding with 50% displacement at 27 microng/ml. [32P]Spectrin dissociated and associated with inverted vesicles with an identical dependence on ionic strength as observed for elution of native spectrin from ghosts. MgCl2, CaCl2 (1 to 4 mM) and EDTA (0.5 to 1 mM) had little effect on binding in the presence of 20 mM KCl, while at low ionic strength, MgCl2 (1 mM) increased binding and inhibited dissociation to the same extent as 10 to 20 mM KCl. Binding was abolished by pretreatment of vesicles with 0.1 M acetic acid, or with 0.1 microng/ml of trypsin. The periodic acid-Schiff-staining bands were unaffected by trypsin digestion which destroyed binding; mild digestion, which decreased binding only 50%, converted Band 3 almost completely to a membrane-bound 50,000-dalton fragment resistant to further proteolysis. These experiments suggest that attachment of spectrin to the cytoplasmic surface of the membrane results from a selective protein-protein interaction which is independent of erythrocyte actin. A direct role of the major sialoglycoprotein or Band 3 as a membrane binding site appears unlikely."}
{"id": "PMID:15999", "title": "Thyroid hormone regulation of beta-adrenergic receptor number.", "content": "The effects of exogenous thyroid hormones (thyroxine and triiodothyronine) on beta-adrenergic receptors in the rat myocardium were investigated. The potent beta-adrenergic antagonist, (-)-[3H]dihydroalprenolol, was used to directly estimate the number and affinity of beta-adrenergic receptors in rat heart membranes from control and hyperthyroid rats. Cardiac membranes from hyperthyroid rats contained 196 +/- 7 fmol of (-)-[3H]dihydroalprenolol binding sites/mg of protein which was significantly (p less than 0.005) greater than the number of binding sites (89 +/- 5 fmol/mg of protein) present in control membranes. The equilibrium dissociation constant (KD) for the interaction of receptors with dihydroalprenolol was the same (2 to 15 nM) in membranes from control and hyperthyroid rats. Similarly, there was no significant difference between the control and hyperthyroid membranes in the affinity of the beta-adrenergic receptor binding sites for the beta-adrenergic agonist isoproterenol. The results of this study demonstrate that thyroid hormones can regulate the number of cardiac beta-adrenergic receptors. The increased numbers of receptors may be responsible, at least in part, for the enhanced catecholamine sensitivity of beta-adrenergic-coupled cardiac responses in the hyperthyroid state.", "contents": "Thyroid hormone regulation of beta-adrenergic receptor number. The effects of exogenous thyroid hormones (thyroxine and triiodothyronine) on beta-adrenergic receptors in the rat myocardium were investigated. The potent beta-adrenergic antagonist, (-)-[3H]dihydroalprenolol, was used to directly estimate the number and affinity of beta-adrenergic receptors in rat heart membranes from control and hyperthyroid rats. Cardiac membranes from hyperthyroid rats contained 196 +/- 7 fmol of (-)-[3H]dihydroalprenolol binding sites/mg of protein which was significantly (p less than 0.005) greater than the number of binding sites (89 +/- 5 fmol/mg of protein) present in control membranes. The equilibrium dissociation constant (KD) for the interaction of receptors with dihydroalprenolol was the same (2 to 15 nM) in membranes from control and hyperthyroid rats. Similarly, there was no significant difference between the control and hyperthyroid membranes in the affinity of the beta-adrenergic receptor binding sites for the beta-adrenergic agonist isoproterenol. The results of this study demonstrate that thyroid hormones can regulate the number of cardiac beta-adrenergic receptors. The increased numbers of receptors may be responsible, at least in part, for the enhanced catecholamine sensitivity of beta-adrenergic-coupled cardiac responses in the hyperthyroid state."}
{"id": "PMID:16000", "title": "Effects of GTP on binding of (3H) glucagon to receptors in rat hepatic plasma membranes.", "content": "In this study, we report the preparation of [3H]glucagon and its characteristics of binding to receptors in the rat liver plasma membrane. Binding of the labeled hormone is optimal at pH 7.0. In the absence of GTP, [3H]glucagon binding to receptors is slow and the time of equilibration is inversely proportional to the hormone concentration. In the presence of GTP, equilibrium is reached within 30 s regardless of hormone levels, and the kinetics of binding are in accord with the kinetics of activation of adenylate cyclase by native glucagon in the presence of the nucleotide. Equilibrium binding measurements indicate that, in the absence of GTP, the binding isotherm is sigmoidal with an apparent Kd of 2 nM. The addition of GTP results in a complex binding isotherm with about 90% of the binding sites having a considerably lower apparent dissociation constant (greater than 10 nM) and a small population of sites having high affinity for the hormone. The binding properties of [3H]glucagon are compared with those of 125I-glucagon, and the implications of the actions of GTP on glucagon binding are discussed in relation to the overall regulation of adenylate cyclase by hormone and the nucleotide.", "contents": "Effects of GTP on binding of (3H) glucagon to receptors in rat hepatic plasma membranes. In this study, we report the preparation of [3H]glucagon and its characteristics of binding to receptors in the rat liver plasma membrane. Binding of the labeled hormone is optimal at pH 7.0. In the absence of GTP, [3H]glucagon binding to receptors is slow and the time of equilibration is inversely proportional to the hormone concentration. In the presence of GTP, equilibrium is reached within 30 s regardless of hormone levels, and the kinetics of binding are in accord with the kinetics of activation of adenylate cyclase by native glucagon in the presence of the nucleotide. Equilibrium binding measurements indicate that, in the absence of GTP, the binding isotherm is sigmoidal with an apparent Kd of 2 nM. The addition of GTP results in a complex binding isotherm with about 90% of the binding sites having a considerably lower apparent dissociation constant (greater than 10 nM) and a small population of sites having high affinity for the hormone. The binding properties of [3H]glucagon are compared with those of 125I-glucagon, and the implications of the actions of GTP on glucagon binding are discussed in relation to the overall regulation of adenylate cyclase by hormone and the nucleotide."}
{"id": "PMID:16001", "title": "Endonuclease from Escherichia coli that acts specifically upon duplex DNA damaged by ultraviolet light, osmium tetroxide, acid, or x-rays.", "content": "An endonuclease which is active upon DNA exposed to ultraviolet light at a photoproduct other than thymine dimers has been extensively purified from Escherichia coli. The small (2.7 S) enzyme is active in the presence of EDTA, has a neutral pH optimum, and is inhibited by tRNA and 1 M NaCl. It has no detectable exonuclease, DNA-N-glycosidase, or ribonuclease activities. The enzyme also nicks duplex DNA exposed to OsO4, x-rays, or acid, but it does not act upon undamaged DNA or irradiated single-stranded DNA. The majority of sites of action in DNA exposed to ultraviolet light or OsO4 appear to be alkali-stable, but those in DNA exposed to x-rays or acid are not. The incisions created by the endonuclease contain 5'-phosphate termini. The enzyme is possibly the same as E. coli endonuclease III described by Radman (Radman, M. (1976) J. Biol. Chem. 251, 1438-1445), but it is distinguishable from the other endodeoxyribonucleases described from that organism.", "contents": "Endonuclease from Escherichia coli that acts specifically upon duplex DNA damaged by ultraviolet light, osmium tetroxide, acid, or x-rays. An endonuclease which is active upon DNA exposed to ultraviolet light at a photoproduct other than thymine dimers has been extensively purified from Escherichia coli. The small (2.7 S) enzyme is active in the presence of EDTA, has a neutral pH optimum, and is inhibited by tRNA and 1 M NaCl. It has no detectable exonuclease, DNA-N-glycosidase, or ribonuclease activities. The enzyme also nicks duplex DNA exposed to OsO4, x-rays, or acid, but it does not act upon undamaged DNA or irradiated single-stranded DNA. The majority of sites of action in DNA exposed to ultraviolet light or OsO4 appear to be alkali-stable, but those in DNA exposed to x-rays or acid are not. The incisions created by the endonuclease contain 5'-phosphate termini. The enzyme is possibly the same as E. coli endonuclease III described by Radman (Radman, M. (1976) J. Biol. Chem. 251, 1438-1445), but it is distinguishable from the other endodeoxyribonucleases described from that organism."}
{"id": "PMID:16002", "title": "A new endonuclease from Escherichia coli acting at apurinic sites in DNA.", "content": "A new DNA endonuclease has been purified 3000-fold from Escherichia coli. The enzyme specifically catalyzes the formation of single strand breaks at apurinic and apyrimidinic sites in DNA, but has no activity on intact or single-stranded DNA. Further, the enzyme shows little or no activity on heavily ultraviolet-irradiated DNA, but cleaves x-irradiated DNA, presumably at apurinic and apyrimidinic sites introduced by the radiation treatment. The enzyme, which is tentatively named endonuclease IV, has no detectable associated exonuclease or DNA N-glycosidase activity and does not seem to be identical with any previously known E. coli endonuclease. Endonuclease IV has no Mg2+ requirement, and is fully active in the presence of EDTA. Enzyme activity is stimulated by 0.2 to 0.3 M NaCl and is unusually salt-resistant. Further, the enzyme is fairly heat-stable, and is not inhibited by tRNA. The sidimentation coefficient, S(o)20,w, is 3.4 S. It seems that endonuclease IV is active in DNA repair.", "contents": "A new endonuclease from Escherichia coli acting at apurinic sites in DNA. A new DNA endonuclease has been purified 3000-fold from Escherichia coli. The enzyme specifically catalyzes the formation of single strand breaks at apurinic and apyrimidinic sites in DNA, but has no activity on intact or single-stranded DNA. Further, the enzyme shows little or no activity on heavily ultraviolet-irradiated DNA, but cleaves x-irradiated DNA, presumably at apurinic and apyrimidinic sites introduced by the radiation treatment. The enzyme, which is tentatively named endonuclease IV, has no detectable associated exonuclease or DNA N-glycosidase activity and does not seem to be identical with any previously known E. coli endonuclease. Endonuclease IV has no Mg2+ requirement, and is fully active in the presence of EDTA. Enzyme activity is stimulated by 0.2 to 0.3 M NaCl and is unusually salt-resistant. Further, the enzyme is fairly heat-stable, and is not inhibited by tRNA. The sidimentation coefficient, S(o)20,w, is 3.4 S. It seems that endonuclease IV is active in DNA repair."}
{"id": "PMID:16003", "title": "Characterization of the m7G(5')pppN-pyrophosphatase activity from HeLa cells.", "content": "The m7(G(5')pppN-pyrophosphatase activity previously detected in HeLa cells has been further characterized. Results from DEAE-cellulose column chromatography and polyacrylamide gel electrophoresis under nondenaturing conditions revealed only one enzyme activity in HeLa cell extracts which was capable of selectively hydrolyzing m7G(5')pppN to yield m7pG + ppN (where N = 2'-O-methylated or unmethylated ribonucleosides or oligonucleotides of up to 8 to 10 nucleosides in length). The majority (approximately 95%) of this activity was found in the cytoplasmic extract but appeared not to be associated with the lysosomal fraction. m7G(5')pppG was hydrolyzed by the partially purified enzyme in the absence of divalent cations at a pH optimum of 7.5 and a temperature optimum of 45 degrees, with a Michaelis constant (Km) of 1.7 micronM. Sedimentation analysis and gel filtration showed the molecular weight of the enzyme as approximately 81,000. Inhibition studies testing the effect of a number of prospective substrates on the rate of m7G(5')pppG hydrolysis have confirmed the importance of the methyl moiety at the N7 position of guanosine for enzyme-substrate interaction. Furthermore, the trimethylated guanosine-containing 5'-terminal structure derived from U-2 RNA was found not to serve as substrate, and 7-methylinosine, unlike 7-methylguanosine, was not an effective inhibitor of m7G(5')pppG hydrolysis. Thus, the 2-amino group of the 7-methylguanosine portion of m7G(5')pppN is also important for substrate interaction with this specific pyrophosphatase.", "contents": "Characterization of the m7G(5')pppN-pyrophosphatase activity from HeLa cells. The m7(G(5')pppN-pyrophosphatase activity previously detected in HeLa cells has been further characterized. Results from DEAE-cellulose column chromatography and polyacrylamide gel electrophoresis under nondenaturing conditions revealed only one enzyme activity in HeLa cell extracts which was capable of selectively hydrolyzing m7G(5')pppN to yield m7pG + ppN (where N = 2'-O-methylated or unmethylated ribonucleosides or oligonucleotides of up to 8 to 10 nucleosides in length). The majority (approximately 95%) of this activity was found in the cytoplasmic extract but appeared not to be associated with the lysosomal fraction. m7G(5')pppG was hydrolyzed by the partially purified enzyme in the absence of divalent cations at a pH optimum of 7.5 and a temperature optimum of 45 degrees, with a Michaelis constant (Km) of 1.7 micronM. Sedimentation analysis and gel filtration showed the molecular weight of the enzyme as approximately 81,000. Inhibition studies testing the effect of a number of prospective substrates on the rate of m7G(5')pppG hydrolysis have confirmed the importance of the methyl moiety at the N7 position of guanosine for enzyme-substrate interaction. Furthermore, the trimethylated guanosine-containing 5'-terminal structure derived from U-2 RNA was found not to serve as substrate, and 7-methylinosine, unlike 7-methylguanosine, was not an effective inhibitor of m7G(5')pppG hydrolysis. Thus, the 2-amino group of the 7-methylguanosine portion of m7G(5')pppN is also important for substrate interaction with this specific pyrophosphatase."}
{"id": "PMID:16004", "title": "Detection of multiple forms of rat liver ornithine decarboxylase.", "content": "Rat liver ornithine decarboxylase induced by injection of thioacetamide has been separated into at least two fractions by covalent chromatography on an activated thiol-Sepharose 4B column. The two major fractions could be distinguished by ion exchange chromatography and electrophoresis on acrylamide gels. In addition, the two forms displayed different Km values for ornithine. Although the two forms are separable, they display identical antigenic properties, pH optima, and they appear to be the same molecular size. The biological significance or the relationship between multiple forms of ornithine decarboxylase is not understood.", "contents": "Detection of multiple forms of rat liver ornithine decarboxylase. Rat liver ornithine decarboxylase induced by injection of thioacetamide has been separated into at least two fractions by covalent chromatography on an activated thiol-Sepharose 4B column. The two major fractions could be distinguished by ion exchange chromatography and electrophoresis on acrylamide gels. In addition, the two forms displayed different Km values for ornithine. Although the two forms are separable, they display identical antigenic properties, pH optima, and they appear to be the same molecular size. The biological significance or the relationship between multiple forms of ornithine decarboxylase is not understood."}
{"id": "PMID:16005", "title": "Production of monospecific antibodies to rat liver ornithine decarboxylase and their use in turnover studies.", "content": "Two forms of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) were purified from the livers of rats which had been treated with thioacetamide for 16 h (for details, see miniprint to Obenrader, M.F., and Prouty, W. F. (1977) J. Biol. Chem. 252, 2860-2865). The enzyme was purified over 7,000-fold from liver cytosol with an overall yield of 8%. Enzyme activity was eluted finally in two distinct fractions by chromatography on activated thiol-Sepharose 4B. Both forms appear to be dimeric proteins having molecular weights of approximately 100,000 by equilibrium sedimentation and analysis on a calibrated Sephadex G-200 column. The apparent subunits are approximately 50,000 daltons as determined by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. Since electrophoresis in the presence of detergent is the only method used here to indicate subunits, the possibility that conditions of sample preparation resulted in splitting of a labile protein cannot be excluded from consideration. Ornithine decarboxylase has a very broad pH-activity curve with an optimum that shifts from pH 7.0 to pH 7.8 as the enzyme is purified. The apparent Km values for a highly purified mixture of the two forms of enzyme for L-ornithine and pyridoxal 5'-phosphate were determined to be 0.13 mM and 0.25 micronM, respectively. Both sodium and potassium chloride were shown to inhibit enzymatic activity; 50% inhibition occurred at 270 mM for each when Km amounts or ornithine were used. Rat liver ornithine decarboxylase antiserum was prepared in rabbits using Form I of the enzyme as the antigen. The antibody was shown to precipitate quantitatively the ornithine decarboxylase activity isolated from induced rat liver and rat ventral prostate. The specificity of the antiserum was demonstrated by rocket immunoelectrophoresis and by gel electrophoresis in the presence of sodium dodecyl sulfate using immunoprecipitates obtained from enzyme preparations labeled either in vivo, with [3H]leucine, or in vitro, by reductive methylation using formaldehyde and sodium [3H]borohydride. The antibody preparation has been used in a titration method to assess the half-life of antigen in livers of rats induced for ornithine decarboxylase by injection of thioacetamide. In two experiments, the t1/2 of activity at the height of induction, following injection of cycloheximide, was 19 and 24 min, while the t1/2 of disappearance of antigen was 28 and 33 min, respectively. In each experiment the t1/2 for antigen was significantly longer than the t1/2 for loss of enzyme activity. Enzyme levels appear to be modulated primarily by synthesis and degradation of antigen. Furthermore, the observation that enzyme activity is lost with a shorter t1/2 than antigen is consistent with the idea that denaturation is an initial step in the degradation of this enzyme...", "contents": "Production of monospecific antibodies to rat liver ornithine decarboxylase and their use in turnover studies. Two forms of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) were purified from the livers of rats which had been treated with thioacetamide for 16 h (for details, see miniprint to Obenrader, M.F., and Prouty, W. F. (1977) J. Biol. Chem. 252, 2860-2865). The enzyme was purified over 7,000-fold from liver cytosol with an overall yield of 8%. Enzyme activity was eluted finally in two distinct fractions by chromatography on activated thiol-Sepharose 4B. Both forms appear to be dimeric proteins having molecular weights of approximately 100,000 by equilibrium sedimentation and analysis on a calibrated Sephadex G-200 column. The apparent subunits are approximately 50,000 daltons as determined by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. Since electrophoresis in the presence of detergent is the only method used here to indicate subunits, the possibility that conditions of sample preparation resulted in splitting of a labile protein cannot be excluded from consideration. Ornithine decarboxylase has a very broad pH-activity curve with an optimum that shifts from pH 7.0 to pH 7.8 as the enzyme is purified. The apparent Km values for a highly purified mixture of the two forms of enzyme for L-ornithine and pyridoxal 5'-phosphate were determined to be 0.13 mM and 0.25 micronM, respectively. Both sodium and potassium chloride were shown to inhibit enzymatic activity; 50% inhibition occurred at 270 mM for each when Km amounts or ornithine were used. Rat liver ornithine decarboxylase antiserum was prepared in rabbits using Form I of the enzyme as the antigen. The antibody was shown to precipitate quantitatively the ornithine decarboxylase activity isolated from induced rat liver and rat ventral prostate. The specificity of the antiserum was demonstrated by rocket immunoelectrophoresis and by gel electrophoresis in the presence of sodium dodecyl sulfate using immunoprecipitates obtained from enzyme preparations labeled either in vivo, with [3H]leucine, or in vitro, by reductive methylation using formaldehyde and sodium [3H]borohydride. The antibody preparation has been used in a titration method to assess the half-life of antigen in livers of rats induced for ornithine decarboxylase by injection of thioacetamide. In two experiments, the t1/2 of activity at the height of induction, following injection of cycloheximide, was 19 and 24 min, while the t1/2 of disappearance of antigen was 28 and 33 min, respectively. In each experiment the t1/2 for antigen was significantly longer than the t1/2 for loss of enzyme activity. Enzyme levels appear to be modulated primarily by synthesis and degradation of antigen. Furthermore, the observation that enzyme activity is lost with a shorter t1/2 than antigen is consistent with the idea that denaturation is an initial step in the degradation of this enzyme..."}
{"id": "PMID:16006", "title": "Reversible binding of Pi by beef heart mitochondrial adenosine triphosphatase.", "content": "Beef heart mitochondrial ATPase (F1) exhibited a single binding site for Pi. The interaction with Pi was reversible, partially dependent on the presence of divalent metal ions, and characterized by a dissociation constant at pH 7.5 of 80 micronM. A variety of substances known to influence oxidative phosphorylation or the activity of the soluble ATPase (F1) also influenced Pi binding by the enzyme. Thus aurovertin, an inhibitor of oxidative phosphorylation, which was bound tightly by F1 and inhibited ATPase activity, enhanced Pi binding via a 4-fold increase in the affinity of the enzyme for Pi (KD = 20 micronM) but did not alter binding stoichiometry. Anions such as SO4(2-), SO3(2-), chromate, and 2,4-dinitrophenolate, which stimulated ATPase activity of F1, also enhanced Pi binding. Inhibitors of ATPase activity such as nickel/bathophenanthroline and the protein ATPase inhibitor of Pullman and Monroy (Pullman, M. E., and Monroy, G. C. (1963) J. Biol. Chem. 238, 3762-3769) inhibited Pi binding. The adenine nucleotides ADP, ATP, and the ATP analog adenylyl imidodiphosphate as well as the Pi analog arsenate, also inhibited Pi binding. The observations suggest that the Pi binding site was located in or near an adenine nucleotide binding site on the molecule.", "contents": "Reversible binding of Pi by beef heart mitochondrial adenosine triphosphatase. Beef heart mitochondrial ATPase (F1) exhibited a single binding site for Pi. The interaction with Pi was reversible, partially dependent on the presence of divalent metal ions, and characterized by a dissociation constant at pH 7.5 of 80 micronM. A variety of substances known to influence oxidative phosphorylation or the activity of the soluble ATPase (F1) also influenced Pi binding by the enzyme. Thus aurovertin, an inhibitor of oxidative phosphorylation, which was bound tightly by F1 and inhibited ATPase activity, enhanced Pi binding via a 4-fold increase in the affinity of the enzyme for Pi (KD = 20 micronM) but did not alter binding stoichiometry. Anions such as SO4(2-), SO3(2-), chromate, and 2,4-dinitrophenolate, which stimulated ATPase activity of F1, also enhanced Pi binding. Inhibitors of ATPase activity such as nickel/bathophenanthroline and the protein ATPase inhibitor of Pullman and Monroy (Pullman, M. E., and Monroy, G. C. (1963) J. Biol. Chem. 238, 3762-3769) inhibited Pi binding. The adenine nucleotides ADP, ATP, and the ATP analog adenylyl imidodiphosphate as well as the Pi analog arsenate, also inhibited Pi binding. The observations suggest that the Pi binding site was located in or near an adenine nucleotide binding site on the molecule."}
{"id": "PMID:16007", "title": "Derepression of amino acid transport by amino acid starvation in rat hepatoma cells.", "content": "Amino acid starvation causes an adaptive increase in the initial rate of transport of selected neutral amino acids in an established line of rat hepatoma cells in tissue culture. After a lag of 30 min, the initial rate of transport of alpha-aminoisobutyric acid (AIB) increases to a maximum after 4 to 6 h starvation of 2 to 3 times that seen in control cells. The increased rate of transport is accompanied by an increase in the Vmax and a modest decrease in the Km for this transport system, and is reversed by readdition of amino acids. The enhancement is specific for amino acids transported by the A or alanine-preferring system (AIB, glycine, proline); uptake of amino acids transported by the L or leucine-preferring system (threonine, phenylalanine, tyrosine, leucine) or the Ly+ system for dibasci amino acids (lysine) is decreased under these conditions. Amino acids which compete with AIB for transport also prevent the starvation-induced increase in AIB transport; amino acids which do not compete fail to prevent the enhancement. Paradoxically threonine, phenylalanine, tryptophan, and tyrosine, which do not compete with AIB for transport, block the enhancement of transport upon amino acid starvation. The starvation-induced enhancement of amino acid transport does not appear to be the result of a release from transinhibition. After 30 min of amino acid starvation, AIB transport is either unchanged or slightly decreased even though amino acid pools are already depleted. Furthermore, loading cells with high concentrations of a single amino acid following a period of amino acid starvation fails to prevent the enhancement of AIB transport, whereas incubation of the cells with the single amino acid for the entire duration of amino acid starvation prevents the enhancement; intracellular amino acid pools are similar under both conditions. The enhancement of amino acid transport requires concomitant RNA and protein synthesis, consistent with the view that the adaptive increase reflects an increased amount of a rate-limiting protein involved in the transport process. Dexamethasone, which dramatically inhibits AIB transport in cells incubated in amino acid-containing medium, both blocks the starvation-induced increase in AIB transport, and causes a time-dependent decrease in transport velocity in cells whose transport has previously been enhanced by starvation.", "contents": "Derepression of amino acid transport by amino acid starvation in rat hepatoma cells. Amino acid starvation causes an adaptive increase in the initial rate of transport of selected neutral amino acids in an established line of rat hepatoma cells in tissue culture. After a lag of 30 min, the initial rate of transport of alpha-aminoisobutyric acid (AIB) increases to a maximum after 4 to 6 h starvation of 2 to 3 times that seen in control cells. The increased rate of transport is accompanied by an increase in the Vmax and a modest decrease in the Km for this transport system, and is reversed by readdition of amino acids. The enhancement is specific for amino acids transported by the A or alanine-preferring system (AIB, glycine, proline); uptake of amino acids transported by the L or leucine-preferring system (threonine, phenylalanine, tyrosine, leucine) or the Ly+ system for dibasci amino acids (lysine) is decreased under these conditions. Amino acids which compete with AIB for transport also prevent the starvation-induced increase in AIB transport; amino acids which do not compete fail to prevent the enhancement. Paradoxically threonine, phenylalanine, tryptophan, and tyrosine, which do not compete with AIB for transport, block the enhancement of transport upon amino acid starvation. The starvation-induced enhancement of amino acid transport does not appear to be the result of a release from transinhibition. After 30 min of amino acid starvation, AIB transport is either unchanged or slightly decreased even though amino acid pools are already depleted. Furthermore, loading cells with high concentrations of a single amino acid following a period of amino acid starvation fails to prevent the enhancement of AIB transport, whereas incubation of the cells with the single amino acid for the entire duration of amino acid starvation prevents the enhancement; intracellular amino acid pools are similar under both conditions. The enhancement of amino acid transport requires concomitant RNA and protein synthesis, consistent with the view that the adaptive increase reflects an increased amount of a rate-limiting protein involved in the transport process. Dexamethasone, which dramatically inhibits AIB transport in cells incubated in amino acid-containing medium, both blocks the starvation-induced increase in AIB transport, and causes a time-dependent decrease in transport velocity in cells whose transport has previously been enhanced by starvation."}
{"id": "PMID:16008", "title": "Adrenodoxin reductase and adrenodoxin. Mechanisms of reduction of ferricyanide and cytochrome c.", "content": "Adrenodoxin reductase, the flavoprotein moiety of the adrenal cortex mitochondrial steroid hydroxylating system, participates in adrenodoxin-dependent cytochrome c and adrenodoxin-independent ferricyanide reduction, with NADPH as electron donor for both of these 1-electron reductions. For ferricyanide reduction, adrenodoxin reductase cycles between oxidized and 2-electron-reduced forms, reoxidation proceeding via the neutral flavin (FAD) semiquinone form (Fig. 9). Addition of adrenodoxin has no effect upon the kinetic parameters of flavoprotein-catalyzed ferricyanide reduction. For cytochrome c reduction, the adrenodoxin reductase-adrenodoxin 1:1 complex has been shown to be the catalytically active species (Lambeth, J. D., McCaslin, D. R., and Kamin, H. (1976) J. Biol. Chem. 251, 7545-7550). Present studies, using stopped flow techniques, have shown that the 2-electron-reduced form of the complex (produced by reaction with 1 eq of NADPH) reacts rapidly with 1 eq of cytochrome c (k approximately or equal to 4.6 s-1), but only slowly with a second cytochrome c (k = 0.1 to 0.3 s-1). However, when a second NADPH is included, two more equivalents of cytochrome are reduced rapidly. Thus, the adrenodoxin reductase-adrenodoxin complex appears to cycle between 1- and 3-electron reduced states, via an intermediate 2-electron-containing form produced by reoxidation by cytochrome (Fig. 10). For ferricyanide reduction by adrenodoxin reductase, the fully reduced and semiquinone forms of flavin each transfer 1 electron at oxidation-reduction potentials which differ by approximately 130 mV. However, adrenodoxin in a complex with adrenodoxin reductase allows electrons of constant potential to be delivered from flavin to cytochrome c via the iron sulfur center...", "contents": "Adrenodoxin reductase and adrenodoxin. Mechanisms of reduction of ferricyanide and cytochrome c. Adrenodoxin reductase, the flavoprotein moiety of the adrenal cortex mitochondrial steroid hydroxylating system, participates in adrenodoxin-dependent cytochrome c and adrenodoxin-independent ferricyanide reduction, with NADPH as electron donor for both of these 1-electron reductions. For ferricyanide reduction, adrenodoxin reductase cycles between oxidized and 2-electron-reduced forms, reoxidation proceeding via the neutral flavin (FAD) semiquinone form (Fig. 9). Addition of adrenodoxin has no effect upon the kinetic parameters of flavoprotein-catalyzed ferricyanide reduction. For cytochrome c reduction, the adrenodoxin reductase-adrenodoxin 1:1 complex has been shown to be the catalytically active species (Lambeth, J. D., McCaslin, D. R., and Kamin, H. (1976) J. Biol. Chem. 251, 7545-7550). Present studies, using stopped flow techniques, have shown that the 2-electron-reduced form of the complex (produced by reaction with 1 eq of NADPH) reacts rapidly with 1 eq of cytochrome c (k approximately or equal to 4.6 s-1), but only slowly with a second cytochrome c (k = 0.1 to 0.3 s-1). However, when a second NADPH is included, two more equivalents of cytochrome are reduced rapidly. Thus, the adrenodoxin reductase-adrenodoxin complex appears to cycle between 1- and 3-electron reduced states, via an intermediate 2-electron-containing form produced by reoxidation by cytochrome (Fig. 10). For ferricyanide reduction by adrenodoxin reductase, the fully reduced and semiquinone forms of flavin each transfer 1 electron at oxidation-reduction potentials which differ by approximately 130 mV. However, adrenodoxin in a complex with adrenodoxin reductase allows electrons of constant potential to be delivered from flavin to cytochrome c via the iron sulfur center..."}
{"id": "PMID:16009", "title": "Alpha-ketoglutarate dehydrogenase complex of Acetobacter xylinum. Purification and regulatory properties.", "content": "The alpha-ketoglutarate dehydrogenase complex of Acetobacter xylinum was purified to homogeneity. It consists of three main polypeptide chains with a total molecular weight of about 2.4 X 10(6). It catalyzes the overall Mg2+ and thiamin pyrophosphate-dependent, NAD+- and CoA-linked oxidative decarboxylation of alpha-ketoglutarate, as well as the partial reactions characteristic of the three enzyme components described for the complex from other sources. Initial velocity studies revealed marked positive cooperativity for the substrate alpha-ketoglutarate (Hill coefficient (nH) = 2.0; concentration of ligand at half-maximum effect (S0.5) = 8 mM). The sigmoidal [alpha-ketoglutarate]-velocity relationship became hyperbolic upon addition of AMP or 3-acetylpyridine adenine dinucleotide (AcPyAD) or in the presence of high concentrations of NAD. S0.5 (alpha-ketoglutarate) decreased to 1 mM, but Vmax was unchanged. Saturation curves for NAD and AMP are sigmoidal (nH = 2) at low alpha-ketoglutarate concentrations and become hyperbolic at high alpha-ketoglutarate concentrations. As judged by S0.5, the relative efficiency of the allosteric effectors is AcPyAD greater than AMP greater than alpha-ketoglutarate- greater than NAD+. Half-maximal changes in nH, S0.5, and activation by AMP occur at a pH significantly different from that of half-maximal activity. A model for the allosteric behavior of the complex is proposed in which the first enzyme component of the complex (E1) is the site for the allosteric interactions and AMP is the primary positive modifier, whereas NAD and AcPyAD act as AMP analogues. The overall reaction is competitively inhibited by NADH with respect to NAD (K1 = 20 micronM) and by succinyl-CoA with respect of CoA (K1 = 3 micronM). The properties of the alpha-ketoglutarate dehydrogenase complex of A. xylinum appear to provide for appropriate partitioning of alpha-ketoglutarate carbon between competing pathways in response to the energy state of the cells.", "contents": "Alpha-ketoglutarate dehydrogenase complex of Acetobacter xylinum. Purification and regulatory properties. The alpha-ketoglutarate dehydrogenase complex of Acetobacter xylinum was purified to homogeneity. It consists of three main polypeptide chains with a total molecular weight of about 2.4 X 10(6). It catalyzes the overall Mg2+ and thiamin pyrophosphate-dependent, NAD+- and CoA-linked oxidative decarboxylation of alpha-ketoglutarate, as well as the partial reactions characteristic of the three enzyme components described for the complex from other sources. Initial velocity studies revealed marked positive cooperativity for the substrate alpha-ketoglutarate (Hill coefficient (nH) = 2.0; concentration of ligand at half-maximum effect (S0.5) = 8 mM). The sigmoidal [alpha-ketoglutarate]-velocity relationship became hyperbolic upon addition of AMP or 3-acetylpyridine adenine dinucleotide (AcPyAD) or in the presence of high concentrations of NAD. S0.5 (alpha-ketoglutarate) decreased to 1 mM, but Vmax was unchanged. Saturation curves for NAD and AMP are sigmoidal (nH = 2) at low alpha-ketoglutarate concentrations and become hyperbolic at high alpha-ketoglutarate concentrations. As judged by S0.5, the relative efficiency of the allosteric effectors is AcPyAD greater than AMP greater than alpha-ketoglutarate- greater than NAD+. Half-maximal changes in nH, S0.5, and activation by AMP occur at a pH significantly different from that of half-maximal activity. A model for the allosteric behavior of the complex is proposed in which the first enzyme component of the complex (E1) is the site for the allosteric interactions and AMP is the primary positive modifier, whereas NAD and AcPyAD act as AMP analogues. The overall reaction is competitively inhibited by NADH with respect to NAD (K1 = 20 micronM) and by succinyl-CoA with respect of CoA (K1 = 3 micronM). The properties of the alpha-ketoglutarate dehydrogenase complex of A. xylinum appear to provide for appropriate partitioning of alpha-ketoglutarate carbon between competing pathways in response to the energy state of the cells."}
{"id": "PMID:16010", "title": "Oxygen-linked CO2 binding to isolated beta subunits of human hemoglobin.", "content": "It is known that most of the oxygen-linked carbamate which is formed in normal adult human hemoglobin (Hb A) is confined to the beta subunits rather than to the alpha subunits. In order to find out if similar differences exist in the isolated protomers of Hb A we have measured the effect of various pressures of carbon dioxide (pCO2) on the oxygen affinity in the following heme pigments: isolated alpha and beta subunits with free --SH groups (alphaSH, betaSH), mercurated beta subunits (betaPMB), myoglobin (Mb), and betaSH/PLP in which the terminal alpha-amino group of betaSH was irreversibly blocked with pyridoxal phosphate (PLP). Similar measurements were done on Hb A and the fraction of oxygen-linked carbamate calculated from the effect of pCO2 (at constant pH) on the oxygen half-saturation pressure (p50). A distinct influence of CO2 on p50 was observed in betaSH which was absent in betaSH/PLP and thus indicates that the terminal alpha-amino group mediates the oxygen-linked binding of CO2 in betaSH as it does in the beta subunits of Hb A. However, the fraction of oxygen-linked carbamate was much less dependent on pH and pCO2 in betaSH than in Hb A. Neither alphaSH, betaPMB, or Mb, all of which are known to exist largely or wholly as monomers but have free terminal alpha-amino groups, showed a shift of p50 upon addition of CO2. As both betaSH and betaSH/PLP were shown to be tetrameric molecules, we conclude from this study that homotetramers composed of isolated beta subunits do exhibit a reciprocal interaction between the binding of O2 and CO2.", "contents": "Oxygen-linked CO2 binding to isolated beta subunits of human hemoglobin. It is known that most of the oxygen-linked carbamate which is formed in normal adult human hemoglobin (Hb A) is confined to the beta subunits rather than to the alpha subunits. In order to find out if similar differences exist in the isolated protomers of Hb A we have measured the effect of various pressures of carbon dioxide (pCO2) on the oxygen affinity in the following heme pigments: isolated alpha and beta subunits with free --SH groups (alphaSH, betaSH), mercurated beta subunits (betaPMB), myoglobin (Mb), and betaSH/PLP in which the terminal alpha-amino group of betaSH was irreversibly blocked with pyridoxal phosphate (PLP). Similar measurements were done on Hb A and the fraction of oxygen-linked carbamate calculated from the effect of pCO2 (at constant pH) on the oxygen half-saturation pressure (p50). A distinct influence of CO2 on p50 was observed in betaSH which was absent in betaSH/PLP and thus indicates that the terminal alpha-amino group mediates the oxygen-linked binding of CO2 in betaSH as it does in the beta subunits of Hb A. However, the fraction of oxygen-linked carbamate was much less dependent on pH and pCO2 in betaSH than in Hb A. Neither alphaSH, betaPMB, or Mb, all of which are known to exist largely or wholly as monomers but have free terminal alpha-amino groups, showed a shift of p50 upon addition of CO2. As both betaSH and betaSH/PLP were shown to be tetrameric molecules, we conclude from this study that homotetramers composed of isolated beta subunits do exhibit a reciprocal interaction between the binding of O2 and CO2."}
{"id": "PMID:16011", "title": "Adenosine triphosphate synthesis by electrochemical proton gradient in vesicles reconstituted from purified adenosine triphosphatase and phospholipids of thermophilic bacterium.", "content": "Vesicles were reconstituted from a purified dicyclohexyl-carbodiimide-sensitive ATPase complex (TF0-F1) and phospholipids of a thermophilic bacterium PS3. These vesicles synthesized ATP from ADP and Pi with energy from an electrochemical proton gradient (delta-micronH+) formed by a pH gradient and an electrical potential across their membranes. Maximal ATP synthesis was achieved by incubating the vesicles in malonate at pH 5.5 with valinomycin, and then rapidly transferring them to a solution of pH 8.4 and 150 mM K+. Under these conditons ATP synthesis continued at a decreasing rate for 30 s at 40 degrees. Appreciable formation of ATP (40 to 150 nmol/mg of TF0-F1) occurred at an initial delta-micronH+ above 205 mV and moderate formation at an initial value above 180 mV. ATP hydrolysis by the vesicles produced a delta-micronH+, and the additions of 32Pi and hexokinase to them resulted in 32Pi esterification. Analysis of the time courses of 32Pi esterification and decays of the pH difference and membrane potential, followed using 9-aminoacridine and 8-anilinonaphthalene-1-sulfonate, respectively, as probes, showed a relationship between delta-micronH+ and the rate of ATP synthesis. These results demonstrate that purified TF0-F1 is itself a reversible H+-translocating ATPase of oxidative phosphorylation.", "contents": "Adenosine triphosphate synthesis by electrochemical proton gradient in vesicles reconstituted from purified adenosine triphosphatase and phospholipids of thermophilic bacterium. Vesicles were reconstituted from a purified dicyclohexyl-carbodiimide-sensitive ATPase complex (TF0-F1) and phospholipids of a thermophilic bacterium PS3. These vesicles synthesized ATP from ADP and Pi with energy from an electrochemical proton gradient (delta-micronH+) formed by a pH gradient and an electrical potential across their membranes. Maximal ATP synthesis was achieved by incubating the vesicles in malonate at pH 5.5 with valinomycin, and then rapidly transferring them to a solution of pH 8.4 and 150 mM K+. Under these conditons ATP synthesis continued at a decreasing rate for 30 s at 40 degrees. Appreciable formation of ATP (40 to 150 nmol/mg of TF0-F1) occurred at an initial delta-micronH+ above 205 mV and moderate formation at an initial value above 180 mV. ATP hydrolysis by the vesicles produced a delta-micronH+, and the additions of 32Pi and hexokinase to them resulted in 32Pi esterification. Analysis of the time courses of 32Pi esterification and decays of the pH difference and membrane potential, followed using 9-aminoacridine and 8-anilinonaphthalene-1-sulfonate, respectively, as probes, showed a relationship between delta-micronH+ and the rate of ATP synthesis. These results demonstrate that purified TF0-F1 is itself a reversible H+-translocating ATPase of oxidative phosphorylation."}
{"id": "PMID:16012", "title": "Pure Renin. Isolation from hog kidney and characterization.", "content": "The pressor enzyme renin (EC 3.4.99.19) was isolated in a pure and stable form from hog kidney by affinity chromatography on a pepstatin/agarose gel followed by three additional steps of conventional chromatography. Destruction of the enzyme by proteolysis during isolation was prevented by chemically eliminating proteases in extracts. The pure preparation was used for the characterization of this enzyme. Renin was found to be a glycoprotein containing glucosamine and possessing binding affinity to concanavalin A. Contrary to previous reports, pure renin is stable at neutral pH either at 4 or -20 degrees for 3 to 8 weeks. It has a molecular weight of 36,400 as determined by equilibrium ultracentrifugation, an isoelectric point of 5.2 and E1%1cm (280 nm) of 9.1. In contrast to crude preparations, the enzyme activity has a broad pH optimum between pH 5.5 and 7.0 for both hog angiotensinogen and the synthetic octapeptide substrate benzyloxycarbonyl-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-beta-naphthylamide. The rate of formation of angiotensin I from hog angiotensinogen at pH 6.0 and 37 degrees was 267 microng/h/microng of renin, or 2000 Goldblatt units/mg of renin. For the synthetic fluorogenic octapeptide substrate benzyloxycarbonyl-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-beta-naphthylamide, a Km of 33 micronM and a Vmax of 0.94 micronmol/h/mg of enzyme were obtained at pH 6.5 and 37 degrees.", "contents": "Pure Renin. Isolation from hog kidney and characterization. The pressor enzyme renin (EC 3.4.99.19) was isolated in a pure and stable form from hog kidney by affinity chromatography on a pepstatin/agarose gel followed by three additional steps of conventional chromatography. Destruction of the enzyme by proteolysis during isolation was prevented by chemically eliminating proteases in extracts. The pure preparation was used for the characterization of this enzyme. Renin was found to be a glycoprotein containing glucosamine and possessing binding affinity to concanavalin A. Contrary to previous reports, pure renin is stable at neutral pH either at 4 or -20 degrees for 3 to 8 weeks. It has a molecular weight of 36,400 as determined by equilibrium ultracentrifugation, an isoelectric point of 5.2 and E1%1cm (280 nm) of 9.1. In contrast to crude preparations, the enzyme activity has a broad pH optimum between pH 5.5 and 7.0 for both hog angiotensinogen and the synthetic octapeptide substrate benzyloxycarbonyl-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-beta-naphthylamide. The rate of formation of angiotensin I from hog angiotensinogen at pH 6.0 and 37 degrees was 267 microng/h/microng of renin, or 2000 Goldblatt units/mg of renin. For the synthetic fluorogenic octapeptide substrate benzyloxycarbonyl-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-beta-naphthylamide, a Km of 33 micronM and a Vmax of 0.94 micronmol/h/mg of enzyme were obtained at pH 6.5 and 37 degrees."}
{"id": "PMID:16013", "title": "Neurospora crassa glutamine synthetase. Translation of specific messenger ribonucleic acid in a cell-free system derived from rabbit reticulocytes.", "content": "The total reticulocyte lysate cell-free protein-synthesizing system was incubated in the presence of Neurospora crassa RNA. With the aid of an antibody directed against purified N. crassa glutamine synthetase, the synthesis of a specific protein was detected. This protein precipitates with antiglutamine synthetase using both direct and indirect procedures, migrates with the same molecular weight as the monomer of N. crassa glutamine synthetase when subjected to acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and chromatographs as N. crassa glutamine synthetase on anthranilate-bound Sepharose. These data indicate the translation of the mRNA that codes for N. crassa glutamine synthetase. This RNA behaves as poly(A)-containing material when fractionated on oly(U)-Sepha-rose.", "contents": "Neurospora crassa glutamine synthetase. Translation of specific messenger ribonucleic acid in a cell-free system derived from rabbit reticulocytes. The total reticulocyte lysate cell-free protein-synthesizing system was incubated in the presence of Neurospora crassa RNA. With the aid of an antibody directed against purified N. crassa glutamine synthetase, the synthesis of a specific protein was detected. This protein precipitates with antiglutamine synthetase using both direct and indirect procedures, migrates with the same molecular weight as the monomer of N. crassa glutamine synthetase when subjected to acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and chromatographs as N. crassa glutamine synthetase on anthranilate-bound Sepharose. These data indicate the translation of the mRNA that codes for N. crassa glutamine synthetase. This RNA behaves as poly(A)-containing material when fractionated on oly(U)-Sepha-rose."}
{"id": "PMID:16014", "title": "Solubilization and properties of mannose and N-acetylglucosamine transferases involved in formation of polyprenyl-sugar intermediates.", "content": "A particulate fraction from porcine aorta catalyzed the incorporation of N-acetylglucosamine (GlcNAc) from UDP-[3H]GlcNAc into both GlcNAc-pyrophosphorylpolyprenol and GlcNAc-GlcNAc-pyrophosphorylpolyprenol. This transfer utilized endogenous lipid and required a divalent cation. Mn2+ was the best metal ion and was optimum at 2.3 mM. This same particulate fraction was previously shown to transfer mannose from GDP-[14C]mannose to endogenous lipid to form mannosylphosphorylpolyprenol (Chambers, J., and Elbein, A.D. (1975) J. Biol. Chem. 250, 6904-6915). Both the GlcNAc activities and the mannose activity were solubilized by treatment of the particulate fraction with the detergent Nonidet P-40. The enzymes were partially purified by chromatography on DEAE-cellulose and on Sephadex G-200. These soluble enzymes required the addition of acceptor lipid for activity. An acidic lipid fraction, isolated from pig liver and having the properties of dolichyl phosphate, was active with either the GlcNAc or the mannose transferase. Chemically synthesized dolichyl phosphate was also active with either of these enzymes. The products formed from either GlcNAc or mannose by the soluble transferases were similar to those formed by the particulate enzyme. Thus the major product formed from UDP-[3H]GlcNAc was GlcNAc-pyrophosphoryldolichol with small amounts of the disaccharide-lipid while the product formed from GDP-[14C]mannose was mannosylphosphoryldolichol.", "contents": "Solubilization and properties of mannose and N-acetylglucosamine transferases involved in formation of polyprenyl-sugar intermediates. A particulate fraction from porcine aorta catalyzed the incorporation of N-acetylglucosamine (GlcNAc) from UDP-[3H]GlcNAc into both GlcNAc-pyrophosphorylpolyprenol and GlcNAc-GlcNAc-pyrophosphorylpolyprenol. This transfer utilized endogenous lipid and required a divalent cation. Mn2+ was the best metal ion and was optimum at 2.3 mM. This same particulate fraction was previously shown to transfer mannose from GDP-[14C]mannose to endogenous lipid to form mannosylphosphorylpolyprenol (Chambers, J., and Elbein, A.D. (1975) J. Biol. Chem. 250, 6904-6915). Both the GlcNAc activities and the mannose activity were solubilized by treatment of the particulate fraction with the detergent Nonidet P-40. The enzymes were partially purified by chromatography on DEAE-cellulose and on Sephadex G-200. These soluble enzymes required the addition of acceptor lipid for activity. An acidic lipid fraction, isolated from pig liver and having the properties of dolichyl phosphate, was active with either the GlcNAc or the mannose transferase. Chemically synthesized dolichyl phosphate was also active with either of these enzymes. The products formed from either GlcNAc or mannose by the soluble transferases were similar to those formed by the particulate enzyme. Thus the major product formed from UDP-[3H]GlcNAc was GlcNAc-pyrophosphoryldolichol with small amounts of the disaccharide-lipid while the product formed from GDP-[14C]mannose was mannosylphosphoryldolichol."}
{"id": "PMID:16015", "title": "Effects of caffeine and other methylxanthines on the development and metabolism of sea urchin eggs. Involvement of NADP and glutathione.", "content": "Methylxanthines (MX) inhibit cell division in sea urchin and clam eggs. This inhibitory effect is not mediated via cAMP. MX also inhibit respiration in marine eggs, at concentrations which inhibit cleavage. Studies showed that no changes occurred in ATP and ADP levels in the presence of inhibitory concentrations of MX, indicating an extra-mitochondrial site of action for the drug. Subsequent studies revealed decreased levels of NADP+ and NADPH, when eggs were incubated with inhibitory concentrations of MX, but no change in levels of NAD+ and NADH. MX did not affect the pentose phosphate shunt pathway and did not have any effect on the enzyme NAD+ -kinase. Further studies showed a marked inhibitory effect on the glutathione reductase activity of MX-treated eggs. Reduced glutathione (GSH) could reverse the cleavage inhibitory effect of MX. Moreover, diamide, a thiol-oxidizing agent specific for GSH in living cells, caused inhibition of cell division in sea urchin eggs. Diamide added to eggs containing mitotic apparatus (MA) could prevent cleavage by causing a dissolution of the formed MA. Both MX and diamide inhibit a Ca2+-activated ATPase in whole eggs. The enzyme can be reactivated by sulfhydryl reducing agents added in the assay mixture. In addition, diamide causes an inhibition of microtubule polymerization, reversible with dithioerythritol. All experimental evidence so far suggests that inhibition of mitosis in sea urchin eggs by MX is mediated by perturbations of the in vivo thiol-disulfide status of target systems, with a primary effect on glutathione levels.", "contents": "Effects of caffeine and other methylxanthines on the development and metabolism of sea urchin eggs. Involvement of NADP and glutathione. Methylxanthines (MX) inhibit cell division in sea urchin and clam eggs. This inhibitory effect is not mediated via cAMP. MX also inhibit respiration in marine eggs, at concentrations which inhibit cleavage. Studies showed that no changes occurred in ATP and ADP levels in the presence of inhibitory concentrations of MX, indicating an extra-mitochondrial site of action for the drug. Subsequent studies revealed decreased levels of NADP+ and NADPH, when eggs were incubated with inhibitory concentrations of MX, but no change in levels of NAD+ and NADH. MX did not affect the pentose phosphate shunt pathway and did not have any effect on the enzyme NAD+ -kinase. Further studies showed a marked inhibitory effect on the glutathione reductase activity of MX-treated eggs. Reduced glutathione (GSH) could reverse the cleavage inhibitory effect of MX. Moreover, diamide, a thiol-oxidizing agent specific for GSH in living cells, caused inhibition of cell division in sea urchin eggs. Diamide added to eggs containing mitotic apparatus (MA) could prevent cleavage by causing a dissolution of the formed MA. Both MX and diamide inhibit a Ca2+-activated ATPase in whole eggs. The enzyme can be reactivated by sulfhydryl reducing agents added in the assay mixture. In addition, diamide causes an inhibition of microtubule polymerization, reversible with dithioerythritol. All experimental evidence so far suggests that inhibition of mitosis in sea urchin eggs by MX is mediated by perturbations of the in vivo thiol-disulfide status of target systems, with a primary effect on glutathione levels."}
{"id": "PMID:16016", "title": "Quantitative studies on the polarization optical properties of striated muscle. I. Birefringence changes of rabbit psoas muscle in the transition from rigor to relaxed state.", "content": "The changes in birefringence in the rigor to relax transition of single triton-extracted rabbit psoas muscle fibers have been investigated with quantitative polarized light techniques. The total birefringence of rest lenght fibers in rigor was (1.46 +/- 0.08) x 10(-3) and increased to (1.67 +/- 0.05) x 10(-3) after Mg-ATP relaxation. Pyrophosphate relaxation increased the total birefringence only slightly, whereas subsequent Mg-ATP relaxation elicited the maximum increase in birefringence. Changes in lattice spacing did not account for the total increase in birefrigence during relaxation. Moreover, the increase in total birefringence was attributable to increases in intrinsic birefringence as well as form birefringence. No change in birefringence was exhibited upon exposure to a relaxation solution after myosin extraction. Synthetic myosin filaments were prepared and treated with relaxation and rigor solutions. The negatively stained filaments treated with a rigor solution had gross irregular projections at either end, while the filaments treated with a relaxing solution were more spindle shaped. The results are compatible with the view that the subfragment-2 moieties of myosin angle away from the myosin aggregates (light meromyosin) to permit the attachment of the subfragment-1 moieties to actin.", "contents": "Quantitative studies on the polarization optical properties of striated muscle. I. Birefringence changes of rabbit psoas muscle in the transition from rigor to relaxed state. The changes in birefringence in the rigor to relax transition of single triton-extracted rabbit psoas muscle fibers have been investigated with quantitative polarized light techniques. The total birefringence of rest lenght fibers in rigor was (1.46 +/- 0.08) x 10(-3) and increased to (1.67 +/- 0.05) x 10(-3) after Mg-ATP relaxation. Pyrophosphate relaxation increased the total birefringence only slightly, whereas subsequent Mg-ATP relaxation elicited the maximum increase in birefringence. Changes in lattice spacing did not account for the total increase in birefrigence during relaxation. Moreover, the increase in total birefringence was attributable to increases in intrinsic birefringence as well as form birefringence. No change in birefringence was exhibited upon exposure to a relaxation solution after myosin extraction. Synthetic myosin filaments were prepared and treated with relaxation and rigor solutions. The negatively stained filaments treated with a rigor solution had gross irregular projections at either end, while the filaments treated with a relaxing solution were more spindle shaped. The results are compatible with the view that the subfragment-2 moieties of myosin angle away from the myosin aggregates (light meromyosin) to permit the attachment of the subfragment-1 moieties to actin."}
{"id": "PMID:16017", "title": "Different sensitivity of DNA in situ in interphase and metaphase chromatin to heat denaturation.", "content": "Heat denaturation of DNA in situ, in unbroken cells, was studied in relation to the cell cycle. DNA in metaphase cells denatured at lower temperatures (8 degrees-10 degrees C lower) than DNA in interphase cells. Among interphase cells, small differences between G1, S, and G2 cells were observed at temperatures above 90 degrees C. The difference between metaphase and interphase cells increased after short pretreatment with formaldehyde, decreased when cells were heated in the presence of 1 mM MgCl2, and was abolished by cell pretreatment with 0.5 N HCl. The results suggest that acid-soluble constituents of chromatin confer local stability to DNA and that the degree of stabilization is lower in metaphase chromosomes than in interphase nuclei. These in situ results remain in contrast to the published data showing no difference in DNA denaturation in chromatin isolated from interphase and metaphase cells. It is likely that factors exist which influence the stability of DNA in situ are associated with the super-structural organization of chromatin in intact nuclei and which are lost during chromatin isolation and solubilization. Since DNA denaturation is assayed after cell cooling, there is also a possibility that the extent of denatured DNA may be influenced by some factors that control strand separation and DNA reassociation. The different stainability of interphase vs. metaphase cells, based on the difference in stability of DNA, offers a method for determining mitotic indices by flow cytofluorometry, and a possible new parameter for sorting cells in metaphase.", "contents": "Different sensitivity of DNA in situ in interphase and metaphase chromatin to heat denaturation. Heat denaturation of DNA in situ, in unbroken cells, was studied in relation to the cell cycle. DNA in metaphase cells denatured at lower temperatures (8 degrees-10 degrees C lower) than DNA in interphase cells. Among interphase cells, small differences between G1, S, and G2 cells were observed at temperatures above 90 degrees C. The difference between metaphase and interphase cells increased after short pretreatment with formaldehyde, decreased when cells were heated in the presence of 1 mM MgCl2, and was abolished by cell pretreatment with 0.5 N HCl. The results suggest that acid-soluble constituents of chromatin confer local stability to DNA and that the degree of stabilization is lower in metaphase chromosomes than in interphase nuclei. These in situ results remain in contrast to the published data showing no difference in DNA denaturation in chromatin isolated from interphase and metaphase cells. It is likely that factors exist which influence the stability of DNA in situ are associated with the super-structural organization of chromatin in intact nuclei and which are lost during chromatin isolation and solubilization. Since DNA denaturation is assayed after cell cooling, there is also a possibility that the extent of denatured DNA may be influenced by some factors that control strand separation and DNA reassociation. The different stainability of interphase vs. metaphase cells, based on the difference in stability of DNA, offers a method for determining mitotic indices by flow cytofluorometry, and a possible new parameter for sorting cells in metaphase."}
{"id": "PMID:16018", "title": "Submitochondrial localization and function of enzymes of glutamine metabolism in avian liver.", "content": "Glutamine synthetase (EC 6.3.1.2) was localized within the matrix compartment of avian liver mitochondria. The submitochondrial localization of this enzyme was determined by the digitonin-Lubrol method of Schnaitman and Greenawalt (35). The matrix fraction contained over 74% of the glutamine synthetase activity and the major proportion of the matirx marker enzymes, malate dehydrogenase (71%), NADP-dependent isocitrate dehydrogenase (83%), and glutamate dehydrogenase (57%). The highest specific activities of these enzymes were also found in the matrix compartment. Oxidation of glutamine by avian liver mitochondria was substantially less than that of glutamate. Bromofuroate, an inhibitor of glutamate dehydrogenase, blocked oxidation of glutamate and of glutamine whereas aminoxyacetate, a transaminase inhibitor, had little or no effect with either substrate. These results indicate that glutamine metabolism is probably initiated by the conversion of glutamine to glutamate rather than to an alpha-keto acid. The localization of a glutaminase activity within avian liver mitochondria plus the absence of an active mitochondrial glutamine transaminase is consistent with the differential effects of the transaminase and glutamate dehydrogenase inhibitors. The high glutamine synthetase activity (40:1) suggests that mitochondrial catabolism of glutamine is minimal, freeing most of the glutamine synthesized for purine (uric acid) biosynthesis.", "contents": "Submitochondrial localization and function of enzymes of glutamine metabolism in avian liver. Glutamine synthetase (EC 6.3.1.2) was localized within the matrix compartment of avian liver mitochondria. The submitochondrial localization of this enzyme was determined by the digitonin-Lubrol method of Schnaitman and Greenawalt (35). The matrix fraction contained over 74% of the glutamine synthetase activity and the major proportion of the matirx marker enzymes, malate dehydrogenase (71%), NADP-dependent isocitrate dehydrogenase (83%), and glutamate dehydrogenase (57%). The highest specific activities of these enzymes were also found in the matrix compartment. Oxidation of glutamine by avian liver mitochondria was substantially less than that of glutamate. Bromofuroate, an inhibitor of glutamate dehydrogenase, blocked oxidation of glutamate and of glutamine whereas aminoxyacetate, a transaminase inhibitor, had little or no effect with either substrate. These results indicate that glutamine metabolism is probably initiated by the conversion of glutamine to glutamate rather than to an alpha-keto acid. The localization of a glutaminase activity within avian liver mitochondria plus the absence of an active mitochondrial glutamine transaminase is consistent with the differential effects of the transaminase and glutamate dehydrogenase inhibitors. The high glutamine synthetase activity (40:1) suggests that mitochondrial catabolism of glutamine is minimal, freeing most of the glutamine synthesized for purine (uric acid) biosynthesis."}
{"id": "PMID:16019", "title": "The influence of culture conditions on the induction of tyrosine aminotransferase by cyclic nucleotides in rat hepatoma cells.", "content": "The increase in tyrosine aminotransferase activity which occurs in rat hepatoma tissue culture (HTC) cells in response to cyclic AMP analogs has been shown to be an enzyme induction, similar to the larger response observed in certain other hepatoma cells and in liver. A specific antibody to tyrosine aminotransferase has been used to show that the number of enzyme molecules and the rate of enzyme synthesis are increased by N6,O2'-dibutyryl cyclic AMP in HTC cells. The effect on tyrosine aminotransferase is also produced by various 8-substituted derivatives of cyclic AMP and occurs whether or not the enzyme has been preinduced with a glucocorticoid. The response of the enzyme is greater when HTC cells are maintained in monolayer than in suspension cultures. Neither cell growth nor serum is required for the response.", "contents": "The influence of culture conditions on the induction of tyrosine aminotransferase by cyclic nucleotides in rat hepatoma cells. The increase in tyrosine aminotransferase activity which occurs in rat hepatoma tissue culture (HTC) cells in response to cyclic AMP analogs has been shown to be an enzyme induction, similar to the larger response observed in certain other hepatoma cells and in liver. A specific antibody to tyrosine aminotransferase has been used to show that the number of enzyme molecules and the rate of enzyme synthesis are increased by N6,O2'-dibutyryl cyclic AMP in HTC cells. The effect on tyrosine aminotransferase is also produced by various 8-substituted derivatives of cyclic AMP and occurs whether or not the enzyme has been preinduced with a glucocorticoid. The response of the enzyme is greater when HTC cells are maintained in monolayer than in suspension cultures. Neither cell growth nor serum is required for the response."}
{"id": "PMID:16020", "title": "The effect of medium pH on rate of growth, neurite formation and acetylcholinesterase activity in mouse neuroblastoma cells in culture.", "content": "Cell division, neurite formation and acetylcholinesterase activity were examined in a clone (NBA2) of mouse neuroblastoma cells maintained for up to 120 hours in medium with pH values between 6.6 and 8.0. Growth rate decreased as pH was reduced from 7.8 to 6.6. Generation time at pH 7.4 was 25 hours, while the rate of cell division was negligible at pH 6.6. The total number of cells at stationary phase was less at the lower pH values. Neurite formation was enhanced markedly as the pH was reduced from 7.4 to 6.6. Acetylcholinesterase activity was 5- to 8-fold greater in cells exposed to medium at pH 6.6 than in cells maintained in medium at pH 7.4. The reduction in the rate of cell division and increases in neurite formation and acetylcholinesterase activity at pH 6.6 were reversible upon exposure of the cells to pH 7.4 medium. Cell viability was greater than 90% at all medium pH values over a period of 120 hours. Uncloned T-59 mouse neuroblastoma cells were affected similarly by changes in pH. These results show that manipulation of the environmental pH can reversibly alter growth, neurite formation, and acetylcholinesterase activity of mouse neuroblastoma cells in culture.", "contents": "The effect of medium pH on rate of growth, neurite formation and acetylcholinesterase activity in mouse neuroblastoma cells in culture. Cell division, neurite formation and acetylcholinesterase activity were examined in a clone (NBA2) of mouse neuroblastoma cells maintained for up to 120 hours in medium with pH values between 6.6 and 8.0. Growth rate decreased as pH was reduced from 7.8 to 6.6. Generation time at pH 7.4 was 25 hours, while the rate of cell division was negligible at pH 6.6. The total number of cells at stationary phase was less at the lower pH values. Neurite formation was enhanced markedly as the pH was reduced from 7.4 to 6.6. Acetylcholinesterase activity was 5- to 8-fold greater in cells exposed to medium at pH 6.6 than in cells maintained in medium at pH 7.4. The reduction in the rate of cell division and increases in neurite formation and acetylcholinesterase activity at pH 6.6 were reversible upon exposure of the cells to pH 7.4 medium. Cell viability was greater than 90% at all medium pH values over a period of 120 hours. Uncloned T-59 mouse neuroblastoma cells were affected similarly by changes in pH. These results show that manipulation of the environmental pH can reversibly alter growth, neurite formation, and acetylcholinesterase activity of mouse neuroblastoma cells in culture."}
{"id": "PMID:16023", "title": "Derivatization and chromatography of nucleosides and nucleotides.", "content": "The aims of this study were to determine the effect of levels of various substances and reaction by-products, which are formed during hydrolysis of nucleic acids, on the derivatization and chromatography of nucleosides; and to investigate the silylation of mono- and dinucleotides. The effect of NaCl, KCl, MgCl2, NH4Cl, and (NH4)2SO4 on silylation and chromatography of nucleosides was studies at various molar excesses of salt. The response values for all nucleosides were studied at various molar excesses of salt. The response values for all nucleosides were significantly affected at molar excess salt present values (MSP) between 1 and 10 for KCl, NaCl, NH4Cl, (NH4)2SO4 and between 0.1 and 1 for MgCl2. It was noted that thymidine was more sensitive than other nucleosides if silylated in presence of these salts. Two chromatographic peaks at retention temperatures (RT) 240 and 251 were obtained for cytidine at MSP values of 10(-3) for NaCl, KCl, and MgCl2, and 10(-4) for NH4Cl and (NH4)2SO4. In a mixture of nucleosides the RT = 251 peak was used for quantitative analysis of cytidine as the RT = 240 peak elutes with guanosine. Thus, these salts have a significant effect on the gas-liquid chromatography of trimethylsilyl (TMS) cytidine in a mixture of nucleosides, especially the RT = 241 peak. The effect of salts on derivatization can be explained in part as follows: (a) reduced derivatization of nucleosides due to a decreased solubility in the solvent system; (b) formation of TMS anion derivatives, e.g. TMS-SO4, TMS-PO4, with a reduced molar excess of BSTFA; (c) metal chelation by Mg ions or other divalent cations with nucleosides or BSTFA; and/or (d) an increased breakdown of TMS derivatives in presence of salt in the sample or on the top 3 in. of the column packing. Also, experiments were made on the effect of other substances such as Tris, phosphate, alkaline phosphatase, and KCl on completeness of silylation. The individual impurities showed no significant effect on the relative weight response (RWR) values of nucleosides; however, when a mixture was used, significantly lower RWR values were observed for all nucleosides except thymidine when using 1000 molar excess of BSTFA greater than 1000 should be used for silylation and chromatography of nucleosides in an RNA hydrolysate. As reported earlier the best derivatization of nucleosides was achieved using closed tube silylation at 150 degrees for 15 min with 225 molar excess BSTFA and chromatography on 4% OV-11 on Supelcoport. In general, the presence of salts and other substances can be significant in quantitative work, thus it is suggested that they be removed using chromatographic cleanup methods. The stability of nucleosides as a function of concentration of HCl, at room temperature was studied and very low RWR values for nucleosides were obtained when stored for 48 h in greater than 0.001 N HCl. Trimethylsilylation of various nucleotides and dinucleotides were made at 15 min as a function of temperature, and at 150 degrees at different times...", "contents": "Derivatization and chromatography of nucleosides and nucleotides. The aims of this study were to determine the effect of levels of various substances and reaction by-products, which are formed during hydrolysis of nucleic acids, on the derivatization and chromatography of nucleosides; and to investigate the silylation of mono- and dinucleotides. The effect of NaCl, KCl, MgCl2, NH4Cl, and (NH4)2SO4 on silylation and chromatography of nucleosides was studies at various molar excesses of salt. The response values for all nucleosides were studied at various molar excesses of salt. The response values for all nucleosides were significantly affected at molar excess salt present values (MSP) between 1 and 10 for KCl, NaCl, NH4Cl, (NH4)2SO4 and between 0.1 and 1 for MgCl2. It was noted that thymidine was more sensitive than other nucleosides if silylated in presence of these salts. Two chromatographic peaks at retention temperatures (RT) 240 and 251 were obtained for cytidine at MSP values of 10(-3) for NaCl, KCl, and MgCl2, and 10(-4) for NH4Cl and (NH4)2SO4. In a mixture of nucleosides the RT = 251 peak was used for quantitative analysis of cytidine as the RT = 240 peak elutes with guanosine. Thus, these salts have a significant effect on the gas-liquid chromatography of trimethylsilyl (TMS) cytidine in a mixture of nucleosides, especially the RT = 241 peak. The effect of salts on derivatization can be explained in part as follows: (a) reduced derivatization of nucleosides due to a decreased solubility in the solvent system; (b) formation of TMS anion derivatives, e.g. TMS-SO4, TMS-PO4, with a reduced molar excess of BSTFA; (c) metal chelation by Mg ions or other divalent cations with nucleosides or BSTFA; and/or (d) an increased breakdown of TMS derivatives in presence of salt in the sample or on the top 3 in. of the column packing. Also, experiments were made on the effect of other substances such as Tris, phosphate, alkaline phosphatase, and KCl on completeness of silylation. The individual impurities showed no significant effect on the relative weight response (RWR) values of nucleosides; however, when a mixture was used, significantly lower RWR values were observed for all nucleosides except thymidine when using 1000 molar excess of BSTFA greater than 1000 should be used for silylation and chromatography of nucleosides in an RNA hydrolysate. As reported earlier the best derivatization of nucleosides was achieved using closed tube silylation at 150 degrees for 15 min with 225 molar excess BSTFA and chromatography on 4% OV-11 on Supelcoport. In general, the presence of salts and other substances can be significant in quantitative work, thus it is suggested that they be removed using chromatographic cleanup methods. The stability of nucleosides as a function of concentration of HCl, at room temperature was studied and very low RWR values for nucleosides were obtained when stored for 48 h in greater than 0.001 N HCl. Trimethylsilylation of various nucleotides and dinucleotides were made at 15 min as a function of temperature, and at 150 degrees at different times..."}
{"id": "PMID:16024", "title": "Chromatographic separation of pyridine and adenine nucleotides on thin layers of poly(ethyleneimine) cellulose.", "content": "The chromatographic properties on thin layers of poly(ethyleneimine) cellulose of sixteen compounds containing the pyridine and/or adenine ring have been studied. Chromatographic mobilities have been examined as a function of the concentration of lithium chloride or sodium formate buffer in the chromatographic solvent. These data provide a rationale for the development of rapid and simple separation methods that should prove useful in the study of pyridine and adenine nucleotide metabolism.", "contents": "Chromatographic separation of pyridine and adenine nucleotides on thin layers of poly(ethyleneimine) cellulose. The chromatographic properties on thin layers of poly(ethyleneimine) cellulose of sixteen compounds containing the pyridine and/or adenine ring have been studied. Chromatographic mobilities have been examined as a function of the concentration of lithium chloride or sodium formate buffer in the chromatographic solvent. These data provide a rationale for the development of rapid and simple separation methods that should prove useful in the study of pyridine and adenine nucleotide metabolism."}
{"id": "PMID:16025", "title": "Thin-layer chromatographic procedure for the detection, isolation and identification of basic psychotropic drugs in urine.", "content": "A procedure is described for the detection and identification of basic psychoactive drugs in urine. In the analytical system proposed, detection is dependent on thin-layer chromatography and chromophoric spraying of the resulting chromatogram. Identification is based on the extractability of the compound at the pH applied, on RF values in two solvents, on colour characteristics after exposure to a sequence of reagents, on fluorescence and UV-absorption characteristics, on retention times in different gas-liquid chromatographic systems and on the behaviour in ion-pair extraction with methyl orange. The procedure has been applied to some narcotic alkaloids and amines which exhibit central stimulant action.", "contents": "Thin-layer chromatographic procedure for the detection, isolation and identification of basic psychotropic drugs in urine. A procedure is described for the detection and identification of basic psychoactive drugs in urine. In the analytical system proposed, detection is dependent on thin-layer chromatography and chromophoric spraying of the resulting chromatogram. Identification is based on the extractability of the compound at the pH applied, on RF values in two solvents, on colour characteristics after exposure to a sequence of reagents, on fluorescence and UV-absorption characteristics, on retention times in different gas-liquid chromatographic systems and on the behaviour in ion-pair extraction with methyl orange. The procedure has been applied to some narcotic alkaloids and amines which exhibit central stimulant action."}
{"id": "PMID:16026", "title": "[Thin-layer chromatography of active compounds from ointments and suppositories followed by direct quantitative analysis by remission (author's transl)].", "content": "The paper describes a method for simultaneous thin-layer chromatographic separation of hydrocortisone, hydrocortisone acetate or hydrocortisone caproate alongside dibucaine hydrochloride, hexachlorophene and clemizole undecylate as well as clemizole hexachlorophenate in ointments and suppositories. Development of thin-layer chromatograms is carried out on silica gel 60 F-254 pre-coated plates. All four active ingredients can be separated on one silica gel plate using one solvent system and determined directly by the remission method using a densitometer. Hydrocortisone and its two esters are measured at 248 nm, dibucaine hydrochloride at 325 nm, hexachlorophene at 300 nm, and clemizole undecylate as well as clemizole hexachlorophenate at 275 nm. Evaluation of thin-layer chromatograms takes place on-line from a linear calibration curve using an IBM 1800 computer. The described method is very suitable for analyses of these active ingredients in drug forms, such as ointments or suppositories and is reproducible with coefficients of variation of 1.29-3.56%.", "contents": "[Thin-layer chromatography of active compounds from ointments and suppositories followed by direct quantitative analysis by remission (author's transl)]. The paper describes a method for simultaneous thin-layer chromatographic separation of hydrocortisone, hydrocortisone acetate or hydrocortisone caproate alongside dibucaine hydrochloride, hexachlorophene and clemizole undecylate as well as clemizole hexachlorophenate in ointments and suppositories. Development of thin-layer chromatograms is carried out on silica gel 60 F-254 pre-coated plates. All four active ingredients can be separated on one silica gel plate using one solvent system and determined directly by the remission method using a densitometer. Hydrocortisone and its two esters are measured at 248 nm, dibucaine hydrochloride at 325 nm, hexachlorophene at 300 nm, and clemizole undecylate as well as clemizole hexachlorophenate at 275 nm. Evaluation of thin-layer chromatograms takes place on-line from a linear calibration curve using an IBM 1800 computer. The described method is very suitable for analyses of these active ingredients in drug forms, such as ointments or suppositories and is reproducible with coefficients of variation of 1.29-3.56%."}
{"id": "PMID:16028", "title": "Itaconic acid carrier ampholytes for isoelectric focusing.", "content": "Commercial carrier ampholytes, obtained by coupling polyethylene polyamines to acrylic acid, exhibit a conductivity minimum in the pH range 5.5-6.5 owing to the lack of appropriate pK values of the polyamine in this pH region. By replacing acrylic with itaconic acid, it has been possible to effect substantial improvements in the pH range 5.5-6.5 as itaconic acid has a pK2 value of 5.45. Upon coupling, the pK of the gramma-carboxyl group remains virtually unaltered. With itoconic acid carrier ampholytes it has been possible to improve the conductivity in the pH range 5.5-6.5 by as much as 400% compared with conventional carrier ampholytes. It is suggected that the commercial products should be supplemented with itaconic acid carrier ampholytes in order to obtain a more uniform conductivity and buffering capacity in the pH range 3-10.", "contents": "Itaconic acid carrier ampholytes for isoelectric focusing. Commercial carrier ampholytes, obtained by coupling polyethylene polyamines to acrylic acid, exhibit a conductivity minimum in the pH range 5.5-6.5 owing to the lack of appropriate pK values of the polyamine in this pH region. By replacing acrylic with itaconic acid, it has been possible to effect substantial improvements in the pH range 5.5-6.5 as itaconic acid has a pK2 value of 5.45. Upon coupling, the pK of the gramma-carboxyl group remains virtually unaltered. With itoconic acid carrier ampholytes it has been possible to improve the conductivity in the pH range 5.5-6.5 by as much as 400% compared with conventional carrier ampholytes. It is suggected that the commercial products should be supplemented with itaconic acid carrier ampholytes in order to obtain a more uniform conductivity and buffering capacity in the pH range 3-10."}
{"id": "PMID:16029", "title": "Determination of clorazepate and its major metabolites in blood and urine by electron capture gas-liquid chromatography.", "content": "A sensitive and specific blood level method employing differential extraction was developed for the determination of clorazepate and its N-desmethyldiazepam metabolite by electron capture gas-liquid chromatography (GLC-ECD). The assay requires the initial extraction of N-desmethyldiazepam, the major metabolite, into benzene-methylene chloride (90:10) from the biological sample made alkaline with 0.1 N NaOH. The samples is then acidified with 2 N HCl to decarboxylate clorazepate to N-desmethyldiazepam, which is then extracted into benzene-methylene chloride (90:10) after adjusting the pH to 12.8 with NaOH. The two extracts are evaporated and the residues are dissolved in benzene which contains griseofulvin as the reference standard. These solutions are assayed by GLC-ECD. The overall recovery and sensitivity limit of the assay for clorazepate is 60+/-5% (S.D.) and 4.0 ng/ml blood, respectively, while that for N-desmethyldiazepam is 95+/-5% (S.D.) and 4.0 ng/ml blood, respectively. The urinary excretion of clorazepate was determined by the measurement of the levels of N-desmethyldiazepam and oxazepam, the major urinary metabolites of clorazepate, both prior to and after enzymatic deconjugation. These methods were applied to the measurement of clorazepate and its metabolites in blood and urine following a single 15-mg dose of clorazepate dipotassium.", "contents": "Determination of clorazepate and its major metabolites in blood and urine by electron capture gas-liquid chromatography. A sensitive and specific blood level method employing differential extraction was developed for the determination of clorazepate and its N-desmethyldiazepam metabolite by electron capture gas-liquid chromatography (GLC-ECD). The assay requires the initial extraction of N-desmethyldiazepam, the major metabolite, into benzene-methylene chloride (90:10) from the biological sample made alkaline with 0.1 N NaOH. The samples is then acidified with 2 N HCl to decarboxylate clorazepate to N-desmethyldiazepam, which is then extracted into benzene-methylene chloride (90:10) after adjusting the pH to 12.8 with NaOH. The two extracts are evaporated and the residues are dissolved in benzene which contains griseofulvin as the reference standard. These solutions are assayed by GLC-ECD. The overall recovery and sensitivity limit of the assay for clorazepate is 60+/-5% (S.D.) and 4.0 ng/ml blood, respectively, while that for N-desmethyldiazepam is 95+/-5% (S.D.) and 4.0 ng/ml blood, respectively. The urinary excretion of clorazepate was determined by the measurement of the levels of N-desmethyldiazepam and oxazepam, the major urinary metabolites of clorazepate, both prior to and after enzymatic deconjugation. These methods were applied to the measurement of clorazepate and its metabolites in blood and urine following a single 15-mg dose of clorazepate dipotassium."}
{"id": "PMID:16030", "title": "Rapid and sensitive electron-capture gas chromatographic method for the determination of pinazepam and its metabolites in human plasma, urine and milk.", "content": "A rapid, sensitive and specific gas-liquid chromatographic method for the measurement of pinazepam and its metabolites in biological fluids is reported. After a single extraction of the sample with toluene, the organic phase is concentrated and, after chromatography on a 3% OV-17 column, measured with an electron-capture detector. The sensitivity was 1.0 ng/ml for pinazepam and 5.0 ng/ml for its metabolites. Plasma levels and urinary excretion in human volunteers and plasma and milk levels in women suffering from anxiety during breastfeeding are reported.", "contents": "Rapid and sensitive electron-capture gas chromatographic method for the determination of pinazepam and its metabolites in human plasma, urine and milk. A rapid, sensitive and specific gas-liquid chromatographic method for the measurement of pinazepam and its metabolites in biological fluids is reported. After a single extraction of the sample with toluene, the organic phase is concentrated and, after chromatography on a 3% OV-17 column, measured with an electron-capture detector. The sensitivity was 1.0 ng/ml for pinazepam and 5.0 ng/ml for its metabolites. Plasma levels and urinary excretion in human volunteers and plasma and milk levels in women suffering from anxiety during breastfeeding are reported."}
{"id": "PMID:16031", "title": "Analysis of warfarin in plasma by high-pressure liquid chromatography.", "content": "An improved high-pressure liquid chromatography method for the estimation of warfarin in plasma was developed. Plasma was acidified and extracted with ethylene dichloride spiked with methylated warfarin [3-(alpha-acetonylbenzyl)-4-methoxy-coumarin] as internal standard. The residue, redissolved in dioxane, was chromatographed on a reversed-phase column using a mobile phase of 40% dioxane in water (pH 4.2) on a high-pressure liquid chromatograph fitted with an UV absorbance detector. Recoveries from extraction, quantitated using tracer amounts of [14C]warfarin and methylated [14C]warfarin were 92.2 +/- 3.16% and 82.33 +/- 1.03%, respectively. The standard curve was linear between o.625 and 5.0 microng/ml. Detection was sensitive to approximately 0.5 microng/ml and specific without the inter ference of normal plasma constituents and warfarin metabolites.", "contents": "Analysis of warfarin in plasma by high-pressure liquid chromatography. An improved high-pressure liquid chromatography method for the estimation of warfarin in plasma was developed. Plasma was acidified and extracted with ethylene dichloride spiked with methylated warfarin [3-(alpha-acetonylbenzyl)-4-methoxy-coumarin] as internal standard. The residue, redissolved in dioxane, was chromatographed on a reversed-phase column using a mobile phase of 40% dioxane in water (pH 4.2) on a high-pressure liquid chromatograph fitted with an UV absorbance detector. Recoveries from extraction, quantitated using tracer amounts of [14C]warfarin and methylated [14C]warfarin were 92.2 +/- 3.16% and 82.33 +/- 1.03%, respectively. The standard curve was linear between o.625 and 5.0 microng/ml. Detection was sensitive to approximately 0.5 microng/ml and specific without the inter ference of normal plasma constituents and warfarin metabolites."}
{"id": "PMID:16032", "title": "Epidemiological studies of Streptococcus pneumoniae in infants: methods of isolating pneumococci.", "content": "A prospective study of the natural history of pneumococcal infection, which involves serial culture studies in healthy infants from 6 weeks of age onward, is in progress in our laboratory. This report describes results of a comparison of several methods for the isolation and identification of Streptococcus pneumoniae from the nasopharynges and throats of these infants. Sheep blood agar, sheep blood agar with gentamicin sulfate (gentamicin agar), and mouse inoculation with 4-h broth cultures were used. Gentamicin agar proved superior to plain sheep blood agar as a solid culture medium, especially in enhancing the recovery of pneumococci from throat cultures. With gentamicin agar, similar carrier rates were found for both culture sites (nasopharynx and throat). In addition, gentamicin agar proved superior to mouse inoculation for the recovery of carrier strains from 131 nasopharyngeal culture samples processed by both methods. Sixty of 131 samples were positive for pneumococci, 25% of which would have been missed had mouse inoculation alone been used. In only three instances did we recover a strain by mouse inoculation that failed to grow on gentamicin agar; conversely, 15 strains were isolated on gentamicin agar but could not be recovered from mice. The latter observation might be explained by the fact that certain carrier strains may be relatively mouse avirulent. The use of blood agar containing gentamicin appears to offer a simple and inexpensive method for the recovery of S. pneumoniae and, in our opinion, provides an ideal method for the identification of pneumococcal carriers as well as for the recovery of these strains from clinical material such as sputum or ear exudates, where other and less fastidious organisms may also be present.", "contents": "Epidemiological studies of Streptococcus pneumoniae in infants: methods of isolating pneumococci. A prospective study of the natural history of pneumococcal infection, which involves serial culture studies in healthy infants from 6 weeks of age onward, is in progress in our laboratory. This report describes results of a comparison of several methods for the isolation and identification of Streptococcus pneumoniae from the nasopharynges and throats of these infants. Sheep blood agar, sheep blood agar with gentamicin sulfate (gentamicin agar), and mouse inoculation with 4-h broth cultures were used. Gentamicin agar proved superior to plain sheep blood agar as a solid culture medium, especially in enhancing the recovery of pneumococci from throat cultures. With gentamicin agar, similar carrier rates were found for both culture sites (nasopharynx and throat). In addition, gentamicin agar proved superior to mouse inoculation for the recovery of carrier strains from 131 nasopharyngeal culture samples processed by both methods. Sixty of 131 samples were positive for pneumococci, 25% of which would have been missed had mouse inoculation alone been used. In only three instances did we recover a strain by mouse inoculation that failed to grow on gentamicin agar; conversely, 15 strains were isolated on gentamicin agar but could not be recovered from mice. The latter observation might be explained by the fact that certain carrier strains may be relatively mouse avirulent. The use of blood agar containing gentamicin appears to offer a simple and inexpensive method for the recovery of S. pneumoniae and, in our opinion, provides an ideal method for the identification of pneumococcal carriers as well as for the recovery of these strains from clinical material such as sputum or ear exudates, where other and less fastidious organisms may also be present."}
{"id": "PMID:16033", "title": "PH metric method for the determination of nicotinic acid in plasma.", "content": "The acidimetric method for the determination of nicotinic acid (NA) using Lactobacillus plantarum ATCC 8014 (Lactobacillus arabinosus 17-5) has been simplified and thus made less time consuming, and the sensitivity has been increased fivefold by replacement of the titration by a pH determination. As the regression of the decrease in pH on the amount of NA was found linear within a range of 1 to 4 ng of NA per ml, the calculations were performed according to the slope-ratio principle. The NA concentration of plasma was determined with a coefficient of variation of 5 to 7%, which rose to about 10% at low NA concentrations. Assays of fasting plasma samples from 13 hyperlipidemic male patients showed a group mean NA concentration of 80 +/- 55 ng/ml (mean +/- 2 standard deviation), before treatment, and 705 +/- 544 ng/ml (mean +/- 2 standard deviation) during therapy with sustained release NA preparations, of which a single dose, ingested during steady-state conditions, doubled or tripled the plasma concentration within 1 to 3 h.", "contents": "PH metric method for the determination of nicotinic acid in plasma. The acidimetric method for the determination of nicotinic acid (NA) using Lactobacillus plantarum ATCC 8014 (Lactobacillus arabinosus 17-5) has been simplified and thus made less time consuming, and the sensitivity has been increased fivefold by replacement of the titration by a pH determination. As the regression of the decrease in pH on the amount of NA was found linear within a range of 1 to 4 ng of NA per ml, the calculations were performed according to the slope-ratio principle. The NA concentration of plasma was determined with a coefficient of variation of 5 to 7%, which rose to about 10% at low NA concentrations. Assays of fasting plasma samples from 13 hyperlipidemic male patients showed a group mean NA concentration of 80 +/- 55 ng/ml (mean +/- 2 standard deviation), before treatment, and 705 +/- 544 ng/ml (mean +/- 2 standard deviation) during therapy with sustained release NA preparations, of which a single dose, ingested during steady-state conditions, doubled or tripled the plasma concentration within 1 to 3 h."}
{"id": "PMID:16034", "title": "Detection of pneumococci in respiratory secretions: clinical evaluation of gentamicin blood agar.", "content": "The use of sheep blood agar containing 5 microng of gentamicin per ml has been suggested as a means of selectively isolating Streptococcus pneumoniae from respiratory secretions. We have tested this method, in parallel with standard methods, on 844 respiratory specimens in a clinical laboratory and have confirmed that the yield of pneumococci can be increased approximately 40% by using agar containing gentamicin. However, since the antibiotic suppresses the growth of staphylococci, group A streptococci, and gram-negative bacilli, gentamicin agar cannot be used as a replacement for the standard method. The requirement for duplicate plating raises the cost per additional pneumococcal isolate to prohibitive amounts. Although the method is useful in studies designed to isolate only pneumococci, it cannot be recommended for the routine clinical laboratory. An unanticipated observation from our study is that the yield of pneumococci in respiratory secretions can be increased 10-fold simply by screening sputum for the presence of leukocytes using the Gram stain. This is in agreement with results reported from other laboratories.", "contents": "Detection of pneumococci in respiratory secretions: clinical evaluation of gentamicin blood agar. The use of sheep blood agar containing 5 microng of gentamicin per ml has been suggested as a means of selectively isolating Streptococcus pneumoniae from respiratory secretions. We have tested this method, in parallel with standard methods, on 844 respiratory specimens in a clinical laboratory and have confirmed that the yield of pneumococci can be increased approximately 40% by using agar containing gentamicin. However, since the antibiotic suppresses the growth of staphylococci, group A streptococci, and gram-negative bacilli, gentamicin agar cannot be used as a replacement for the standard method. The requirement for duplicate plating raises the cost per additional pneumococcal isolate to prohibitive amounts. Although the method is useful in studies designed to isolate only pneumococci, it cannot be recommended for the routine clinical laboratory. An unanticipated observation from our study is that the yield of pneumococci in respiratory secretions can be increased 10-fold simply by screening sputum for the presence of leukocytes using the Gram stain. This is in agreement with results reported from other laboratories."}
{"id": "PMID:16035", "title": "Reactivation of Newcastle Disease Virus Neutralized by Antibody.", "content": "In an effort to improve current technology for detection of Newcastle disease virus in convalescent birds, a procedure has been developed for efficient reactivation of virus that has been neutralized by antibody. The reactivation capabilities of fluorocarbon treatment, ultrasonic treatment, pH extremes, and proteolytic digestion were evaluated using the LaSota strain of virus. Reactivation was maximum after proteolytic digestion with either trypsin or papain, and reactivation effciency was up to 100%, depending on the enzyme used for digestion and the amount of antibody in the neutralization mixture. Reactivation at pH extremes was considerably less efficient than reactiviation by proteolytic digestion, and neither fluorocarbon nor ultrasonic treatments effectively recovered antibody-neutralized Newcastle disease virus.", "contents": "Reactivation of Newcastle Disease Virus Neutralized by Antibody. In an effort to improve current technology for detection of Newcastle disease virus in convalescent birds, a procedure has been developed for efficient reactivation of virus that has been neutralized by antibody. The reactivation capabilities of fluorocarbon treatment, ultrasonic treatment, pH extremes, and proteolytic digestion were evaluated using the LaSota strain of virus. Reactivation was maximum after proteolytic digestion with either trypsin or papain, and reactivation effciency was up to 100%, depending on the enzyme used for digestion and the amount of antibody in the neutralization mixture. Reactivation at pH extremes was considerably less efficient than reactiviation by proteolytic digestion, and neither fluorocarbon nor ultrasonic treatments effectively recovered antibody-neutralized Newcastle disease virus."}
{"id": "PMID:16036", "title": "Rapid method for determining nitrate utilization by yeasts.", "content": "A test for the nitrate-reductase activity in yeasts has been developed, in which the reaction may be read after only 10 min of incubation. The rapidity of the test is due to the optimization of pH, substrate concentration, and temperature for the reaction.", "contents": "Rapid method for determining nitrate utilization by yeasts. A test for the nitrate-reductase activity in yeasts has been developed, in which the reaction may be read after only 10 min of incubation. The rapidity of the test is due to the optimization of pH, substrate concentration, and temperature for the reaction."}
{"id": "PMID:16037", "title": "Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.", "content": "Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role.", "contents": "Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy. Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role."}
{"id": "PMID:16038", "title": "Hydrolysis of the elastase substrate succinyltrialanine nitroanilide by a metal-dependent enzyme in rheumatoid synovial fluid.", "content": "A new type of enzyme hydrolyzing the elastase substrate succinyl-L-alanyl-L-alanine-4-nitroanilide has been found in cell-free rheuma todi synovial fluid. Normal plasma and osteoarthritic synovial fluid contained relatively little enzyme. The pH optimum was 8.0. Unexpectedly, the enzyme activity was not due to leukocyte elastase or any proteinase bound to alpha2-macroglobulin. The enzyme activity was metal-dependent being inhibited by chelating agents but not by di-isopropylfluorophos phate or thiol-blocking reagents. Gel chromatography showed the enzyme activity was associated with material of high molecular weight. On Sepharose 4B chromatography two-thirds of the activity eluted in the void volume and one-third in a position of about 106 mol wt. Utracentrifugation showed that both components were associated with lipid. The buoyant density of the higher molecular weight material was 1.15-1.22 g/ml., and that of lower molecular weight material was 1.2-1.33 g/ml. No latency of the enzyme was revealed by freezing and thawing or treatment with detergents. The nature of the enzyme is discussed. It is likely to be a proteinase possibly bound to some kind of membrane fragment.", "contents": "Hydrolysis of the elastase substrate succinyltrialanine nitroanilide by a metal-dependent enzyme in rheumatoid synovial fluid. A new type of enzyme hydrolyzing the elastase substrate succinyl-L-alanyl-L-alanine-4-nitroanilide has been found in cell-free rheuma todi synovial fluid. Normal plasma and osteoarthritic synovial fluid contained relatively little enzyme. The pH optimum was 8.0. Unexpectedly, the enzyme activity was not due to leukocyte elastase or any proteinase bound to alpha2-macroglobulin. The enzyme activity was metal-dependent being inhibited by chelating agents but not by di-isopropylfluorophos phate or thiol-blocking reagents. Gel chromatography showed the enzyme activity was associated with material of high molecular weight. On Sepharose 4B chromatography two-thirds of the activity eluted in the void volume and one-third in a position of about 106 mol wt. Utracentrifugation showed that both components were associated with lipid. The buoyant density of the higher molecular weight material was 1.15-1.22 g/ml., and that of lower molecular weight material was 1.2-1.33 g/ml. No latency of the enzyme was revealed by freezing and thawing or treatment with detergents. The nature of the enzyme is discussed. It is likely to be a proteinase possibly bound to some kind of membrane fragment."}
{"id": "PMID:16040", "title": "Metabolic studies in patients with nadolol: oral and intravenous administration.", "content": "Nadolol-14C, 2,3-cis-5-(3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol, a nonselective beta-adrenergic blocking agent, was administered orally and intravenously at 2-mg doses to patients with mild cases of essential hypertension. Terminal plasma half-times after oral and intravenous doses were an average of 12.2 and 9.8 hours, respectively. After oral doses, an average of 24.6 and 76.9 per cent of the dose was excreted in urine and feces, respectively, whereas, after intravenous doses, an average of 72.9 and 23.3 per cent of the dose was excreted by the same routes. Calculations of absorption, based on urinary excretion and on areas under the plasma concentration-versus-time curves, indicated that oral doses of nadolol-14C were absorbed to the extent of 33.6+/-2.4 per cent (+/- S.E.). The average overall volume of distribution after intravenous administration was 2.09+/-0.51 1./kg (+/- S.E.), and the average volume of the central compartment was 0.30+/-0.04 1./kg. Only unchanged nadolol-14C was excreted in the urine and feces of patients after either oral or intravenous administration of the drug.", "contents": "Metabolic studies in patients with nadolol: oral and intravenous administration. Nadolol-14C, 2,3-cis-5-(3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol, a nonselective beta-adrenergic blocking agent, was administered orally and intravenously at 2-mg doses to patients with mild cases of essential hypertension. Terminal plasma half-times after oral and intravenous doses were an average of 12.2 and 9.8 hours, respectively. After oral doses, an average of 24.6 and 76.9 per cent of the dose was excreted in urine and feces, respectively, whereas, after intravenous doses, an average of 72.9 and 23.3 per cent of the dose was excreted by the same routes. Calculations of absorption, based on urinary excretion and on areas under the plasma concentration-versus-time curves, indicated that oral doses of nadolol-14C were absorbed to the extent of 33.6+/-2.4 per cent (+/- S.E.). The average overall volume of distribution after intravenous administration was 2.09+/-0.51 1./kg (+/- S.E.), and the average volume of the central compartment was 0.30+/-0.04 1./kg. Only unchanged nadolol-14C was excreted in the urine and feces of patients after either oral or intravenous administration of the drug."}
{"id": "PMID:16044", "title": "Electroencephalographic responses to photic stimulation in habitual smokers and nonsmokers.", "content": "Two studies are reported in which electroencephalograms (EEGs) of habitual cigarette smokers and of nonsmokers were taken before and after they were required to smoke a cigarette. The EEGs were scored for incidence of EEG \"driving\" responses to photic stimulation, an index that appears to reflect the balance between central adrenergic and cholinergic nervous systems. The findings suggest that smokers tend to have a central autonomic balance less in favor of adrenergic functioning than do nonsmokers. Cigarette smoking may alleviate a possible central adrenergic insufficiency of smokers. These findings suggest a solution to \"Nesbitt's paradox,\" which has reference to the fact that while nicotine is a central adrenergic stimulant, smokers describe the effect of smoking in sedational terms (i.e., as relaxing or calming).", "contents": "Electroencephalographic responses to photic stimulation in habitual smokers and nonsmokers. Two studies are reported in which electroencephalograms (EEGs) of habitual cigarette smokers and of nonsmokers were taken before and after they were required to smoke a cigarette. The EEGs were scored for incidence of EEG \"driving\" responses to photic stimulation, an index that appears to reflect the balance between central adrenergic and cholinergic nervous systems. The findings suggest that smokers tend to have a central autonomic balance less in favor of adrenergic functioning than do nonsmokers. Cigarette smoking may alleviate a possible central adrenergic insufficiency of smokers. These findings suggest a solution to \"Nesbitt's paradox,\" which has reference to the fact that while nicotine is a central adrenergic stimulant, smokers describe the effect of smoking in sedational terms (i.e., as relaxing or calming)."}
{"id": "PMID:16039", "title": "A method for evaluating anxiolytic sedatives.", "content": "Although anxiolytic sedatives are widely used in clinical practice, the methodology for assessing treatment effect of these compounds has not been well developed. The present double-blind study was designed to refine methodology for evaluating anxiolytics. Choice of rating scale, patient selection, maintenance of the double-blind status, the subjects' environment during the study, and the subjects' understanding of the study are discussed as considerations in reducing sources of variability and bias in the study of anxiolytics. After placebo prescreening, 14 subjects with diagnoses of anxiety recieved 3 to 6 mg lorazepam daily for four weeks, while 14 control subjects received placebo. The Hamilton Anxiety Rating Scale (HARS) and the Wang Anxiety Rating Scale (WARS), with its Anxiolytic Adjunct Scale (AAS), were used to assess changes in anxiety. The Wang and Hamilton ratings correlated well at both comparison periods. Lorazepam demonstrated significant superiority to placebo and produced no serious adverse effects. Anxiolytic efficacy did not differ significantly among the four weekly ratings.", "contents": "A method for evaluating anxiolytic sedatives. Although anxiolytic sedatives are widely used in clinical practice, the methodology for assessing treatment effect of these compounds has not been well developed. The present double-blind study was designed to refine methodology for evaluating anxiolytics. Choice of rating scale, patient selection, maintenance of the double-blind status, the subjects' environment during the study, and the subjects' understanding of the study are discussed as considerations in reducing sources of variability and bias in the study of anxiolytics. After placebo prescreening, 14 subjects with diagnoses of anxiety recieved 3 to 6 mg lorazepam daily for four weeks, while 14 control subjects received placebo. The Hamilton Anxiety Rating Scale (HARS) and the Wang Anxiety Rating Scale (WARS), with its Anxiolytic Adjunct Scale (AAS), were used to assess changes in anxiety. The Wang and Hamilton ratings correlated well at both comparison periods. Lorazepam demonstrated significant superiority to placebo and produced no serious adverse effects. Anxiolytic efficacy did not differ significantly among the four weekly ratings."}
{"id": "PMID:16041", "title": "Comparison of triazolam, flurazepam, and placebo as hypnotics in geriatric patients with insomnia.", "content": "The safety and efficacy of 0.25 mg triazolam were compared to those of 15 mg flurazepam and placebo in 41 geriatric outpatients suffering from insomnia. The patients were randomly assigned to one of the three treatment groups. The medication was taken at bedtime for 28 days. Tolerance development was also studied. Triazolam was found to be significantly better than placebo in how much the medication helped the patients sleep, in sleep onset, in duration of sleep, number of nighttime awakenings, in quality (depth) of sleep, and in feeling of restfulness in the morning. Triazolam was significantly better than flurazepam in duration of sleep and was rated higher than flurazepam in all other variables. Flurazepam was significantly better than placebo in only two variables--onset of sleep and quality (depth) of sleep. Side effects were reported in each treatment group, and one patient on placebo discontinued because of side effects. There was no decrease in hypnotic effect over this four-week period, therefore, no evidence of tolerance development on either of the active compounds. Both active compounds provided the same amount of relief from insomnia after four weeks as they had after one week. Laboratory analyses and poststudy physical examinations showed no deleterious effects over the four-week period.", "contents": "Comparison of triazolam, flurazepam, and placebo as hypnotics in geriatric patients with insomnia. The safety and efficacy of 0.25 mg triazolam were compared to those of 15 mg flurazepam and placebo in 41 geriatric outpatients suffering from insomnia. The patients were randomly assigned to one of the three treatment groups. The medication was taken at bedtime for 28 days. Tolerance development was also studied. Triazolam was found to be significantly better than placebo in how much the medication helped the patients sleep, in sleep onset, in duration of sleep, number of nighttime awakenings, in quality (depth) of sleep, and in feeling of restfulness in the morning. Triazolam was significantly better than flurazepam in duration of sleep and was rated higher than flurazepam in all other variables. Flurazepam was significantly better than placebo in only two variables--onset of sleep and quality (depth) of sleep. Side effects were reported in each treatment group, and one patient on placebo discontinued because of side effects. There was no decrease in hypnotic effect over this four-week period, therefore, no evidence of tolerance development on either of the active compounds. Both active compounds provided the same amount of relief from insomnia after four weeks as they had after one week. Laboratory analyses and poststudy physical examinations showed no deleterious effects over the four-week period."}
{"id": "PMID:16048", "title": "The use of drugs for behavior modification as it relates to the practice of optometry--Part II.", "content": "Drugs used in behavior modification are considered with respect to type, specific agents, conditions for which they are used, and associated ocular and visual side effects. Relevant types include narcotic analgesics, sedatives and hypnotics, antipsychotics, antianxiety drugs, antidepressants, psychomotor stimulating agents, caffeine, the antihistamines, estrogen and progestins, vitamins, disulfiram, and illicit drugs and chemicals.", "contents": "The use of drugs for behavior modification as it relates to the practice of optometry--Part II. Drugs used in behavior modification are considered with respect to type, specific agents, conditions for which they are used, and associated ocular and visual side effects. Relevant types include narcotic analgesics, sedatives and hypnotics, antipsychotics, antianxiety drugs, antidepressants, psychomotor stimulating agents, caffeine, the antihistamines, estrogen and progestins, vitamins, disulfiram, and illicit drugs and chemicals."}
{"id": "PMID:16053", "title": "Burns of the foot.", "content": "The most severe trauma a patient can sustain is a major burn. When a person is seriously burned, initial care begins with maintaining an adequate airway and adequate blood volume and urinary output by intravenous fluids. After the patient has been stabilized, the wound is of primary importance, and postage stamp split thickness grafts are used for skin coverage. When these are secure and a maximal range of motion has been obtained, reconstructive procedures should be started.", "contents": "Burns of the foot. The most severe trauma a patient can sustain is a major burn. When a person is seriously burned, initial care begins with maintaining an adequate airway and adequate blood volume and urinary output by intravenous fluids. After the patient has been stabilized, the wound is of primary importance, and postage stamp split thickness grafts are used for skin coverage. When these are secure and a maximal range of motion has been obtained, reconstructive procedures should be started."}
{"id": "PMID:16055", "title": "Soft tissue trauma of the foot.", "content": "Before and since podiatric physicians began treating patients with foot ailments, soft tissue trauma has been a major challenge. Soft tissues, the outermost tissues, are traumatized with more ease and frequency than are skeletal tissues within. Management of soft tissue trauma must be deliberate and directed toward not only immediate, but also long-term results. Timing and expertise in management are essential for the successful treatment of soft tissue trauma of the foot.", "contents": "Soft tissue trauma of the foot. Before and since podiatric physicians began treating patients with foot ailments, soft tissue trauma has been a major challenge. Soft tissues, the outermost tissues, are traumatized with more ease and frequency than are skeletal tissues within. Management of soft tissue trauma must be deliberate and directed toward not only immediate, but also long-term results. Timing and expertise in management are essential for the successful treatment of soft tissue trauma of the foot."}
{"id": "PMID:16057", "title": "[Pendulum testes: a degraded from of cryptorchism].", "content": "In 22 cases of sterility we have been able to single out under the name of \"pendulum testes\" a syndrome showing the following features: --clinically, testes that are often small and soft and normally found in the lower part of the scrotum, but with a tendency to ride up toward the inguinal canal and stay there so that an attempt to bring them down manually into the scrotum in unsuccessful; --cytologically, often accompanied by very poor sperm formation, and; --histologically, showing tubule pathology. We approach this picture as that of crytorchidism for in our opinion pendulum testis is a degraded form of latter. This leads us to discuss for both conditions problems of classification and indications for treatment.", "contents": "[Pendulum testes: a degraded from of cryptorchism]. In 22 cases of sterility we have been able to single out under the name of \"pendulum testes\" a syndrome showing the following features: --clinically, testes that are often small and soft and normally found in the lower part of the scrotum, but with a tendency to ride up toward the inguinal canal and stay there so that an attempt to bring them down manually into the scrotum in unsuccessful; --cytologically, often accompanied by very poor sperm formation, and; --histologically, showing tubule pathology. We approach this picture as that of crytorchidism for in our opinion pendulum testis is a degraded form of latter. This leads us to discuss for both conditions problems of classification and indications for treatment."}
{"id": "PMID:16060", "title": "An evaluation of elution techniques in the study of immune complex glomerulonephritis.", "content": "Antigen and antibody from glomerular immune complex deposits in rabbits with experimental bovine serum albumin-(BSA) induced chronic serum sickness (CSS) were quantitated in elutes from kidneys in which a portion of the antigen and antibody had been radiolabeled. The largest quantities of 125I BSA eluted with 1 M roprionic acid at pH 2.7 (86%) and 0.1 M borate buffer at pH 11.25 (80%). However, these buffers yielded less functional anti-BSA antibody than 0.02 M citrate buffer at pH 3.2 (344 mug/g kidney). Citrate buffer-eluted anti-BSA antibody was reactive in immunodiffusion, immunofluorescence, and radiolabeled BSA binding test systems, but complement fixation was impaired relative to chaotropic ion-eluted antibody. It was found that up to 75% of the eluted antibody was lost to further study by recombination with eluted BSA. This could be prevented by fractionation of the dissociated eluate before neutralization. IgG fractionated eluates were successfully fluorescein conjugated or radiolabeled for use as reagents. Elution of cryostat sections of CSS kidney was also studied; BSA, IgG, and complement (C3) eluted in parallel, and sub-microgram quantities of anti-BSA antibody were recovered.", "contents": "An evaluation of elution techniques in the study of immune complex glomerulonephritis. Antigen and antibody from glomerular immune complex deposits in rabbits with experimental bovine serum albumin-(BSA) induced chronic serum sickness (CSS) were quantitated in elutes from kidneys in which a portion of the antigen and antibody had been radiolabeled. The largest quantities of 125I BSA eluted with 1 M roprionic acid at pH 2.7 (86%) and 0.1 M borate buffer at pH 11.25 (80%). However, these buffers yielded less functional anti-BSA antibody than 0.02 M citrate buffer at pH 3.2 (344 mug/g kidney). Citrate buffer-eluted anti-BSA antibody was reactive in immunodiffusion, immunofluorescence, and radiolabeled BSA binding test systems, but complement fixation was impaired relative to chaotropic ion-eluted antibody. It was found that up to 75% of the eluted antibody was lost to further study by recombination with eluted BSA. This could be prevented by fractionation of the dissociated eluate before neutralization. IgG fractionated eluates were successfully fluorescein conjugated or radiolabeled for use as reagents. Elution of cryostat sections of CSS kidney was also studied; BSA, IgG, and complement (C3) eluted in parallel, and sub-microgram quantities of anti-BSA antibody were recovered."}
{"id": "PMID:16061", "title": "Studies on cellular inhibition and serum-blocking factors in 28 human patients given marrow grafts from HLA identical siblings.", "content": "Fifteen patients with aplastic anemia and 13 with acute leukemia were studied 36 to 1547 days after treatment with high-dose cyclophosphamide and/or total-body irradiation and marrow transplantation from HLA identical siblings. Peripheral blood lymphocytes from patients and normals (marrow donors and healthy unrelated individuals) were tested for cell inhibition (CI) of cultured skin fibroblasts from both patients and donors by using the microcytotoxicity assay. In addition, blocking of CI by factors in patient serum was studied. Three groups of patients were studied. Patients in group I were stable long-term survivors without evidence of graft-vs-host diseases (GVHD) between 250 to 1547 days postgrafting. Patients in group II were short-term survivors with or without acute GVHD between 36 and 144 days postgrafting. Patients in group III had chronic GVHD either at the time of testing or developed chronic GVHD subsequent to CI testing between days 61 and 960 postgrafting. Eleven of 14 patients in group I showed absence of both CI and serum blocking and three showed CI and blocking. Patients in group II without acute GVHD showed absence of CI and serum blocking on three occasions, presence of CI and blocking on four occasions, and CI without blocking on three occasions. Patients in group II with acute GVHD showed absence of CI on one occasion and presence of CI and blocking on three occasions. Patients in group III showed absence of CI and blocking on seven occasions and CI without blocking on two occasions. These results suggest that the maintenance of stable graft-host tolerance in long-term survivors after marrow grafting from HLA identical donors does not depend on the presence of serum-blocking factors. Short-term survivors with and without GVHD showed a spectrum of in vitro reactivity with 50% of the patients showing serum-blocking factors, and these results did not appear to be correlated with presence or absence of acute GVHD. Finally, results of the microcytotoxicity assays failed to provide insight into the mechanism of chronic GVHD.", "contents": "Studies on cellular inhibition and serum-blocking factors in 28 human patients given marrow grafts from HLA identical siblings. Fifteen patients with aplastic anemia and 13 with acute leukemia were studied 36 to 1547 days after treatment with high-dose cyclophosphamide and/or total-body irradiation and marrow transplantation from HLA identical siblings. Peripheral blood lymphocytes from patients and normals (marrow donors and healthy unrelated individuals) were tested for cell inhibition (CI) of cultured skin fibroblasts from both patients and donors by using the microcytotoxicity assay. In addition, blocking of CI by factors in patient serum was studied. Three groups of patients were studied. Patients in group I were stable long-term survivors without evidence of graft-vs-host diseases (GVHD) between 250 to 1547 days postgrafting. Patients in group II were short-term survivors with or without acute GVHD between 36 and 144 days postgrafting. Patients in group III had chronic GVHD either at the time of testing or developed chronic GVHD subsequent to CI testing between days 61 and 960 postgrafting. Eleven of 14 patients in group I showed absence of both CI and serum blocking and three showed CI and blocking. Patients in group II without acute GVHD showed absence of CI and serum blocking on three occasions, presence of CI and blocking on four occasions, and CI without blocking on three occasions. Patients in group II with acute GVHD showed absence of CI on one occasion and presence of CI and blocking on three occasions. Patients in group III showed absence of CI and blocking on seven occasions and CI without blocking on two occasions. These results suggest that the maintenance of stable graft-host tolerance in long-term survivors after marrow grafting from HLA identical donors does not depend on the presence of serum-blocking factors. Short-term survivors with and without GVHD showed a spectrum of in vitro reactivity with 50% of the patients showing serum-blocking factors, and these results did not appear to be correlated with presence or absence of acute GVHD. Finally, results of the microcytotoxicity assays failed to provide insight into the mechanism of chronic GVHD."}
{"id": "PMID:16062", "title": "Characteristics of tyrosinase in B16 melanoma.", "content": "Tyrosine hydroxylase, dopa oxidase, and peroxidase activities were studied in soluble fractions of B16 melanoma tumor homogenates by polyacrylamide gel disc electrophoresis. Stained gels were scanned photometrically and gel slices were assayed radiometrically. In these preparations, the two bands of tyrosine hydroxylating activity were completely separated from the peroxidase activity but coincided with two major bands of dopa oxidase activity. The third dopa oxidase band coincided with the single band of peroxidase activity. The soluble fraction of cultured cell homogenates had no peroxidase activity, but the two tyrosine hydroxylase bands coincided exactly with the two dopa oxidase bands. Therefore, in the soluble fraction of the murine melanoma bifunctional tyrosinase does exist as two electrophoretically separable forms which are independent of peroxidase.", "contents": "Characteristics of tyrosinase in B16 melanoma. Tyrosine hydroxylase, dopa oxidase, and peroxidase activities were studied in soluble fractions of B16 melanoma tumor homogenates by polyacrylamide gel disc electrophoresis. Stained gels were scanned photometrically and gel slices were assayed radiometrically. In these preparations, the two bands of tyrosine hydroxylating activity were completely separated from the peroxidase activity but coincided with two major bands of dopa oxidase activity. The third dopa oxidase band coincided with the single band of peroxidase activity. The soluble fraction of cultured cell homogenates had no peroxidase activity, but the two tyrosine hydroxylase bands coincided exactly with the two dopa oxidase bands. Therefore, in the soluble fraction of the murine melanoma bifunctional tyrosinase does exist as two electrophoretically separable forms which are independent of peroxidase."}
{"id": "PMID:16063", "title": "Epidermal nucleases. II. The multiplicity of ribonucleases in guinea-pig epidermis.", "content": "Ribonuclease activity has been extracted from adult guinea-pig epidermis by sequential homogenization in dilute sodium acetate and sulfuric acid. The extracts were subjected to ammonium sulfate fractionation and to affinity and ion exchange chromatography. Three ribonucleases (I, II, III) were separated from the sodium acetate extract and 6(A, B1, B2, B3, C, D) were isolated from the sulfuric acid extract. The degree of purification varies from 65-fold to 8,700-fold and the apparent molecular weights of the active forms of 8 of the 9 ribonucleases range from 10,000 to 36,500. No phosphodiesterase activity is present in any of the 9 fractions, but there is alkaline phosphatase activity in one (I) and deoxyribonuclease activity in a second (B3). Two of the ribonucleases have acid pH optima (a1, B3), while the others are most active between PHs 6.8 and 7.8. The activity of 4 of the fractions is sensitive to added EDTA (III, A, B2, B3,), but no stimulatory metal ions were found. Low concentrations of the polyamine spermidine enhanced the activity of 3-fractions (III, C, D). Yeast ribonucleic acid is degraded exonucleolytically by 2 fractions (I, A) and endonucleolytically by the remaining 7. In experiments with homopolyribonucleotide substrates, poly U was generally the preferred substrate. Substantial hydrolysis of poly A occurred with 2 fractions (A, B3) and slight hydrolysis of poly G with 2 other fractions (B2, C).", "contents": "Epidermal nucleases. II. The multiplicity of ribonucleases in guinea-pig epidermis. Ribonuclease activity has been extracted from adult guinea-pig epidermis by sequential homogenization in dilute sodium acetate and sulfuric acid. The extracts were subjected to ammonium sulfate fractionation and to affinity and ion exchange chromatography. Three ribonucleases (I, II, III) were separated from the sodium acetate extract and 6(A, B1, B2, B3, C, D) were isolated from the sulfuric acid extract. The degree of purification varies from 65-fold to 8,700-fold and the apparent molecular weights of the active forms of 8 of the 9 ribonucleases range from 10,000 to 36,500. No phosphodiesterase activity is present in any of the 9 fractions, but there is alkaline phosphatase activity in one (I) and deoxyribonuclease activity in a second (B3). Two of the ribonucleases have acid pH optima (a1, B3), while the others are most active between PHs 6.8 and 7.8. The activity of 4 of the fractions is sensitive to added EDTA (III, A, B2, B3,), but no stimulatory metal ions were found. Low concentrations of the polyamine spermidine enhanced the activity of 3-fractions (III, C, D). Yeast ribonucleic acid is degraded exonucleolytically by 2 fractions (I, A) and endonucleolytically by the remaining 7. In experiments with homopolyribonucleotide substrates, poly U was generally the preferred substrate. Substantial hydrolysis of poly A occurred with 2 fractions (A, B3) and slight hydrolysis of poly G with 2 other fractions (B2, C)."}
{"id": "PMID:16064", "title": "Temperature-sensitive mutants of Streptococcus pneumoniae. I. Preparation and characterization in vitro of temperature-sensitive mutants of type I S. pneumoniae.", "content": "After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide.", "contents": "Temperature-sensitive mutants of Streptococcus pneumoniae. I. Preparation and characterization in vitro of temperature-sensitive mutants of type I S. pneumoniae. After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide."}
{"id": "PMID:16065", "title": "Purification and immunochemical characterization of the outer membrane complex of Bacteroides melaninogenicus subspecies asaccharolyticus.", "content": "Morphologic study of Bacteroides melaninogenicus subspecies asaccharolyticus by electron microscopy disclosed the presence of a capsule and a cell wall structure otherwise typical of a gram-negative organism. An outer membrane complex was isolated with use of gentle methods. Relative purity of the preparation was confirmed by electron microscopy and by the formation of a single band in a sucrose density gradient. Gel chromatography was used for separation of the major components of the membrane. Antigenicity of the first component, a protein-polysaccharide complex, which cross-reacted with antiserum to another strain of the same subspecies. This component probably represents the capsular antigen and may prove to be the basis for serogrouping. The second membrane fraction differed chemically from the first fraction and represents the lipopolysaccharide component of the outer membrane. Notably, this component lacks 2-keto-3-deoxyoctonate, one of the backbone sugars of aerobic, gram-negative lipopolysaccharides.", "contents": "Purification and immunochemical characterization of the outer membrane complex of Bacteroides melaninogenicus subspecies asaccharolyticus. Morphologic study of Bacteroides melaninogenicus subspecies asaccharolyticus by electron microscopy disclosed the presence of a capsule and a cell wall structure otherwise typical of a gram-negative organism. An outer membrane complex was isolated with use of gentle methods. Relative purity of the preparation was confirmed by electron microscopy and by the formation of a single band in a sucrose density gradient. Gel chromatography was used for separation of the major components of the membrane. Antigenicity of the first component, a protein-polysaccharide complex, which cross-reacted with antiserum to another strain of the same subspecies. This component probably represents the capsular antigen and may prove to be the basis for serogrouping. The second membrane fraction differed chemically from the first fraction and represents the lipopolysaccharide component of the outer membrane. Notably, this component lacks 2-keto-3-deoxyoctonate, one of the backbone sugars of aerobic, gram-negative lipopolysaccharides."}
{"id": "PMID:16068", "title": "A simple method for the separate measurement of transcobalamins I, II, and III: normal ranges in serum and plasma in men and women.", "content": "A simple method for the separate measurement of the unsaturated binding capacity of the three main circulating vitamin B12 binders, transcobalamins (TCs) I, II, and III,  is described. The method involves batch separation of TC I and III from TC II by means of Quso G32, followed by batch separation of TC I from TC II with the use of diethylaminoethyl. The present study provides the first complete comparison of unsaturated TC I, II, and III in serum versus fluoridinated plasma of a single group of normal men versus women. There are consistently higher values in serum, largely due to an in vitro increment of TC III, prevented by NaF. The results are compared with values for some of these parameters obtained by others with the use of different methods, providing a standard for evaluating significance of results by various methods.", "contents": "A simple method for the separate measurement of transcobalamins I, II, and III: normal ranges in serum and plasma in men and women. A simple method for the separate measurement of the unsaturated binding capacity of the three main circulating vitamin B12 binders, transcobalamins (TCs) I, II, and III,  is described. The method involves batch separation of TC I and III from TC II by means of Quso G32, followed by batch separation of TC I from TC II with the use of diethylaminoethyl. The present study provides the first complete comparison of unsaturated TC I, II, and III in serum versus fluoridinated plasma of a single group of normal men versus women. There are consistently higher values in serum, largely due to an in vitro increment of TC III, prevented by NaF. The results are compared with values for some of these parameters obtained by others with the use of different methods, providing a standard for evaluating significance of results by various methods."}
{"id": "PMID:16069", "title": "Mechanism by which neutral phosphate infusion elevates urine PCO2.", "content": "Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics.", "contents": "Mechanism by which neutral phosphate infusion elevates urine PCO2. Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics."}
{"id": "PMID:16070", "title": "Kinetics of the cyanate-hemoglobin reaction in whole blood.", "content": "The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia.", "contents": "Kinetics of the cyanate-hemoglobin reaction in whole blood. The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia."}
{"id": "PMID:16071", "title": "Use of a competitive protein-binding assay for adenosine 3':5'-phosphate for the study of bovine corpus luteum adenylate cyclase.", "content": "The use of a competitive protein-binding assay for cyclic AMP, utilizing the binding protein purified from bovine adrenal cortex, for the study of adenylate cyclase activity of the washed 600 g sediment of bovine corpus luteum is validated. A specific assay for cyclic AMP could only be achieved by removal of the degradation products of ATP on a precipitate of nascent BaSO4. Simple dilution of the sample before assay was not sufficient to eliminate interference from degradation products of ATP. An observed variability in optimal ATP substrate and tissue concentrations is though to reflect variability in the enzymic profile of the cyclic corpus luteum. Optima with respect to F-, Mg2+ and pH are more clearly defined and are similar to those reported for adenylate cyclase systems for other tissues.", "contents": "Use of a competitive protein-binding assay for adenosine 3':5'-phosphate for the study of bovine corpus luteum adenylate cyclase. The use of a competitive protein-binding assay for cyclic AMP, utilizing the binding protein purified from bovine adrenal cortex, for the study of adenylate cyclase activity of the washed 600 g sediment of bovine corpus luteum is validated. A specific assay for cyclic AMP could only be achieved by removal of the degradation products of ATP on a precipitate of nascent BaSO4. Simple dilution of the sample before assay was not sufficient to eliminate interference from degradation products of ATP. An observed variability in optimal ATP substrate and tissue concentrations is though to reflect variability in the enzymic profile of the cyclic corpus luteum. Optima with respect to F-, Mg2+ and pH are more clearly defined and are similar to those reported for adenylate cyclase systems for other tissues."}
{"id": "PMID:16072", "title": "Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder.", "content": "Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV.", "contents": "Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder. Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV."}
{"id": "PMID:16073", "title": "The Ly phenotype of suppressor T cells arising in mice subjected to a graft-versus-host reaction.", "content": "T cells with helper and suppressor functions arising during graft-versus-host reaction (B6 vs. BDF1) have been characterized with respect to their Ly surface antigens. Helper cells were found to express the phenotype Ly 1+2- and suppressor cells the phenotype Ly 1+2+. Ly 1-2+ T cells had no suppressive effect in this system. T cells of the host did not contribute to either activity.", "contents": "The Ly phenotype of suppressor T cells arising in mice subjected to a graft-versus-host reaction. T cells with helper and suppressor functions arising during graft-versus-host reaction (B6 vs. BDF1) have been characterized with respect to their Ly surface antigens. Helper cells were found to express the phenotype Ly 1+2- and suppressor cells the phenotype Ly 1+2+. Ly 1-2+ T cells had no suppressive effect in this system. T cells of the host did not contribute to either activity."}
{"id": "PMID:16078", "title": "The pH-dependent rate of action of local anesthetics on the node of Ranvier.", "content": "Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility.", "contents": "The pH-dependent rate of action of local anesthetics on the node of Ranvier. Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility."}
{"id": "PMID:16079", "title": "Lack of a regulatory function for glutamine synthetase protein in the synthesis of glutamate dehydrogenase and nitrite reductase in Escherichia coli K12.", "content": "Synthesis of glutamine synthetase (GS) in anaerobic batch cultures of Escherichia coli was repressed when excess NH4+ was available, but derepressed during growth with a poor nitrogen source. In wild-type bacteria there was only a weak inverse correlation between the activities of GS and glutamate dehydrogenase (GDH) during growth in various media. No positive correlations were found between the activities of GS and nitrite reductase, or between GS and cytochrome c552: both of these proteins were synthesized normally by mutants that contained no active GS. Although activities of GS and GDH were low in two mutants that are unable to synthesize cytochrome c552 or reduce nitrite because of defects in the nirA gene, the nirA defect was separated from the GS and GDH defects by transduction with bacteriophage P1. Attempts to show that catabolite repression of proline oxidase synthesis could be relieved during NH4+ starvation also failed. It is, therefore, unlikely that nitrite reduction or proline oxidation by E. coli are under positive control by GS protein. The regulation of the synthesis of enzymes for the utilization of secondary nitrogen sources in E. coli, therefore, different from that in Klebsiella aerogenes, but is similar to that in Salmonella typhimurium.", "contents": "Lack of a regulatory function for glutamine synthetase protein in the synthesis of glutamate dehydrogenase and nitrite reductase in Escherichia coli K12. Synthesis of glutamine synthetase (GS) in anaerobic batch cultures of Escherichia coli was repressed when excess NH4+ was available, but derepressed during growth with a poor nitrogen source. In wild-type bacteria there was only a weak inverse correlation between the activities of GS and glutamate dehydrogenase (GDH) during growth in various media. No positive correlations were found between the activities of GS and nitrite reductase, or between GS and cytochrome c552: both of these proteins were synthesized normally by mutants that contained no active GS. Although activities of GS and GDH were low in two mutants that are unable to synthesize cytochrome c552 or reduce nitrite because of defects in the nirA gene, the nirA defect was separated from the GS and GDH defects by transduction with bacteriophage P1. Attempts to show that catabolite repression of proline oxidase synthesis could be relieved during NH4+ starvation also failed. It is, therefore, unlikely that nitrite reduction or proline oxidation by E. coli are under positive control by GS protein. The regulation of the synthesis of enzymes for the utilization of secondary nitrogen sources in E. coli, therefore, different from that in Klebsiella aerogenes, but is similar to that in Salmonella typhimurium."}
{"id": "PMID:16080", "title": "Evaluation of the role of methional, 2-keto-4-methylthiobutyric acid and peroxidase in ethylene formation by Escherichia coli.", "content": "During growth of Escherichia coli strain SPA O in the presence of methionine, an intermediate accumulates in the medium. This intermediate reacts with 2,4-dinitrophenylhydrazine, and can be degraded to ethylene either enzymically or photochemically, the latter being stimulated by the addition of a flavin. The pH optimum for the photochemical degradation of this intermediate and 2-keto-4-methylthiobutyric acid (KMBA) is pH 3 whereas the optimum for methional is pH 6. The enzyme which converts the intermediate to ethylene also converts KMBA to ethylene and has many of the properties of a peroxidase including inhibition by catalase, cyanide, azide and anaerobiosis. The enzyme which synthesizes the intermediate is not known but requires oxygen and pyridoxal phosphate. A pathway for ethylene biosynthesis is proposed in which methionine is converted to KMBA which can be degraded either by peroxidase or in a flavin-mediated photochemical reaction. Its relevance to the properties of other ethylene-producing bacteria and to the proposed pathway of ethylene release by higher plants is discussed.", "contents": "Evaluation of the role of methional, 2-keto-4-methylthiobutyric acid and peroxidase in ethylene formation by Escherichia coli. During growth of Escherichia coli strain SPA O in the presence of methionine, an intermediate accumulates in the medium. This intermediate reacts with 2,4-dinitrophenylhydrazine, and can be degraded to ethylene either enzymically or photochemically, the latter being stimulated by the addition of a flavin. The pH optimum for the photochemical degradation of this intermediate and 2-keto-4-methylthiobutyric acid (KMBA) is pH 3 whereas the optimum for methional is pH 6. The enzyme which converts the intermediate to ethylene also converts KMBA to ethylene and has many of the properties of a peroxidase including inhibition by catalase, cyanide, azide and anaerobiosis. The enzyme which synthesizes the intermediate is not known but requires oxygen and pyridoxal phosphate. A pathway for ethylene biosynthesis is proposed in which methionine is converted to KMBA which can be degraded either by peroxidase or in a flavin-mediated photochemical reaction. Its relevance to the properties of other ethylene-producing bacteria and to the proposed pathway of ethylene release by higher plants is discussed."}
{"id": "PMID:16081", "title": "Effect of chaotropic salts and protein denaturants on the thermal stability of mouse fibroblast interferon.", "content": "Altering the aqueous environment, especially with agents that affect hydrogen bonds, markedly affects the stability of mouse L cell interferon. Low pH stabilizes interferon whereas high pH labilizes it; heavy water further enhances interferon thermostability at pH 2 but not at pH 9. Exposure to the protein denaturants, 4 M-guanidine hydrochloride and 6 M-urea, significantly decreases the activity of interferon at pH 2 and pH9; however, the residual interferon activity is relatively thermostable. Certain chaotropic salts protect interferon against thermal destruction, and in terms of effectiveness, their sequence is in the order SCN- greater than 1- larger than or equal to Cl- = CiO4- - Br- greater than NO3-. Interferon becomes more stable to heat as the NaSCN concentration is increased from 0-25 M to 2-0 M. Molecular sieve chromatography of interferon in the presence of 1-5 M-NaSCN at pH 7 shows a shift in its apparent mol. wt. from 25000 to 42000. Unlike most proteins, the unfolded conformation of interferon appears to be more stable to heat than the molecule with a smaller Stokes' radius.", "contents": "Effect of chaotropic salts and protein denaturants on the thermal stability of mouse fibroblast interferon. Altering the aqueous environment, especially with agents that affect hydrogen bonds, markedly affects the stability of mouse L cell interferon. Low pH stabilizes interferon whereas high pH labilizes it; heavy water further enhances interferon thermostability at pH 2 but not at pH 9. Exposure to the protein denaturants, 4 M-guanidine hydrochloride and 6 M-urea, significantly decreases the activity of interferon at pH 2 and pH9; however, the residual interferon activity is relatively thermostable. Certain chaotropic salts protect interferon against thermal destruction, and in terms of effectiveness, their sequence is in the order SCN- greater than 1- larger than or equal to Cl- = CiO4- - Br- greater than NO3-. Interferon becomes more stable to heat as the NaSCN concentration is increased from 0-25 M to 2-0 M. Molecular sieve chromatography of interferon in the presence of 1-5 M-NaSCN at pH 7 shows a shift in its apparent mol. wt. from 25000 to 42000. Unlike most proteins, the unfolded conformation of interferon appears to be more stable to heat than the molecule with a smaller Stokes' radius."}
{"id": "PMID:16082", "title": "Changes in primary process expression in hospitalized schizophrenics treated with phenothiazines: two projective tasks compared.", "content": "It was hypothesized that primary process expression on Gottschalk's Five Minute Verbalization Task (FMV) would be more representative of clinical status in schizophrenia than primary process expression on the Rorschach. Ss were 21 males and 15 females, ages 19-41 years, newly admitted to the hospital and treated with phenothiazines. The FMV was administered at predrug, five weeks, and 13 weeks, and the Rorschach at predrug and five weeks. Primary process scoring was according to the Holt system. Clinical improvement was measured by the Lorr IMPS and the Burdock Ward Behavior Scale. Over time, Ss produced less primary process on the FMV (p less than .001), while on the Rorschach scores did not change significantly. The scores on the FMV but not on the Rorschach paralleled some measures of clinical improvement (p less than .05). In a factor analysis, scores on the FMV and Rorschach were related to specific but different symptoms. It was concluded that the FMV was more effective in determining clinical improvement, while the Rorschach was perhaps more valuable in assessing the nature of the primary process thinking.", "contents": "Changes in primary process expression in hospitalized schizophrenics treated with phenothiazines: two projective tasks compared. It was hypothesized that primary process expression on Gottschalk's Five Minute Verbalization Task (FMV) would be more representative of clinical status in schizophrenia than primary process expression on the Rorschach. Ss were 21 males and 15 females, ages 19-41 years, newly admitted to the hospital and treated with phenothiazines. The FMV was administered at predrug, five weeks, and 13 weeks, and the Rorschach at predrug and five weeks. Primary process scoring was according to the Holt system. Clinical improvement was measured by the Lorr IMPS and the Burdock Ward Behavior Scale. Over time, Ss produced less primary process on the FMV (p less than .001), while on the Rorschach scores did not change significantly. The scores on the FMV but not on the Rorschach paralleled some measures of clinical improvement (p less than .05). In a factor analysis, scores on the FMV and Rorschach were related to specific but different symptoms. It was concluded that the FMV was more effective in determining clinical improvement, while the Rorschach was perhaps more valuable in assessing the nature of the primary process thinking."}
{"id": "PMID:16083", "title": "Effect of curare on responses to different putative neurotransmitters in Aplysia neurons.", "content": "We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, gamma-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na+, a fast hyperpolarizing Cl-, or a slow hyperpolarizing K+ conductance increase. All responses resulting from either Na+ or Cl- conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by less than or equal to 10-4 M curare. GABA responses were less sensitive and were often only depressed by 10-3 M curare. K+ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na+, Cl-, and K+, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses.", "contents": "Effect of curare on responses to different putative neurotransmitters in Aplysia neurons. We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, gamma-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na+, a fast hyperpolarizing Cl-, or a slow hyperpolarizing K+ conductance increase. All responses resulting from either Na+ or Cl- conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by less than or equal to 10-4 M curare. GABA responses were less sensitive and were often only depressed by 10-3 M curare. K+ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na+, Cl-, and K+, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses."}
{"id": "PMID:16091", "title": "Role of the posterior hypothalamus in the development of acute brain swelling.", "content": "Destructive stereotaxic lesions were made in the posterior hypothalamus, unilaterally or bilaterally, in 26 dogs. In 21 dogs the intracranial pressure (ICP) was maintained in normal range, and in five dogs the ICP was artificially elevated to 300 to 400 mm h2o, preceding the procedures to the hypothlamus. Arterial oxygen and carbon dioxide pressure ((PaO2 and PaCO2) were maintained in the normal range. Before and after each procedure, systemic arterial pressure (SAP) was elevated by intravenous injection of norepinephrine (5 X 10(-3) mg/kg) to determined whether the ICP increases coincidentally with elevation of the systemic arterial pressure. The intracranial pressure/mean arterial pressure ratio of elevation by injection of norepinephrine was not significant regardless of the level of the ICP, or of uni-or bilateral lesions of the hypothalamus. The authors conclude that dysfunction of posterior hypothalamus does not play a specific role in the development of vasomotor paralysis leading to acute brain swelling, under conditons of normal or moderately raised ICP with normal PaCO2 and Pato2 levels.", "contents": "Role of the posterior hypothalamus in the development of acute brain swelling. Destructive stereotaxic lesions were made in the posterior hypothalamus, unilaterally or bilaterally, in 26 dogs. In 21 dogs the intracranial pressure (ICP) was maintained in normal range, and in five dogs the ICP was artificially elevated to 300 to 400 mm h2o, preceding the procedures to the hypothlamus. Arterial oxygen and carbon dioxide pressure ((PaO2 and PaCO2) were maintained in the normal range. Before and after each procedure, systemic arterial pressure (SAP) was elevated by intravenous injection of norepinephrine (5 X 10(-3) mg/kg) to determined whether the ICP increases coincidentally with elevation of the systemic arterial pressure. The intracranial pressure/mean arterial pressure ratio of elevation by injection of norepinephrine was not significant regardless of the level of the ICP, or of uni-or bilateral lesions of the hypothalamus. The authors conclude that dysfunction of posterior hypothalamus does not play a specific role in the development of vasomotor paralysis leading to acute brain swelling, under conditons of normal or moderately raised ICP with normal PaCO2 and Pato2 levels."}
{"id": "PMID:16092", "title": "Studies on the labeling of streptokinase with 99mTc for use as a radiopharmaceutical in the detection of deep-vein thrombosis: concise communication.", "content": "Streptokinase was labeled with 99mTc using both stannous chloride and stannous pyrophosphate as reducing agents. Sixty to seventy-five percent of the 99m Tc was incorporated into streptokinase using stannous chloride as a reducing agent at pH 1-2, wheras 50-60% was incorporated using stannous pyrophosphate at neutral pH. Increasing the pH from 2 to 7 in the presence of stannous chloride caused the release of 15-20% of the protein-bound 99mTc. Incorporation of 99mTc into protein was relatively slow: labeling required 2-3 hr at room temperature. The concentration of stannous pyrophosphate required for optimum labeling varied between 10(-5) and 10(-2) M. Polyacrylamide-gel electrophoresis showed that the filler substance in commercial streptokinase was also labeled with 99mTc. However pure streptokinase gave a homogenous protein band after polyacrylamide-gel electrophoresis. This protein band coincided with the peak of streptokinase-bound 99mTc. The results obtained may partially explain why 99mTc-labeled streptokinase lacks the necessary specificity for the satisfactory location of blood clots in vivo.", "contents": "Studies on the labeling of streptokinase with 99mTc for use as a radiopharmaceutical in the detection of deep-vein thrombosis: concise communication. Streptokinase was labeled with 99mTc using both stannous chloride and stannous pyrophosphate as reducing agents. Sixty to seventy-five percent of the 99m Tc was incorporated into streptokinase using stannous chloride as a reducing agent at pH 1-2, wheras 50-60% was incorporated using stannous pyrophosphate at neutral pH. Increasing the pH from 2 to 7 in the presence of stannous chloride caused the release of 15-20% of the protein-bound 99mTc. Incorporation of 99mTc into protein was relatively slow: labeling required 2-3 hr at room temperature. The concentration of stannous pyrophosphate required for optimum labeling varied between 10(-5) and 10(-2) M. Polyacrylamide-gel electrophoresis showed that the filler substance in commercial streptokinase was also labeled with 99mTc. However pure streptokinase gave a homogenous protein band after polyacrylamide-gel electrophoresis. This protein band coincided with the peak of streptokinase-bound 99mTc. The results obtained may partially explain why 99mTc-labeled streptokinase lacks the necessary specificity for the satisfactory location of blood clots in vivo."}
{"id": "PMID:16099", "title": "Integration of clinical and academic nursing at the hospital clinical unit level.", "content": "In a successful attempt to solve problems in Pediatric Nursing at the Medical University of South Carolina, a Department Chairman was named Director-Chairman of Pediatric Nursing and given operational authority over both clinical and academic nursing in Pediatrics. The results were more efficient administration, a higher quality of patient care and an enriched environment for student learning.", "contents": "Integration of clinical and academic nursing at the hospital clinical unit level. In a successful attempt to solve problems in Pediatric Nursing at the Medical University of South Carolina, a Department Chairman was named Director-Chairman of Pediatric Nursing and given operational authority over both clinical and academic nursing in Pediatrics. The results were more efficient administration, a higher quality of patient care and an enriched environment for student learning."}
{"id": "PMID:16100", "title": "Effect of dietary DL-ethionine and/or DL-methionine on egg laying and activities of some cytoplasmic NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica.", "content": "The effect of dietary DL-ethionine and/or DL-methionine on egg laying, and activities of some NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica was investigated. A 0.30% DL-ethionine plus 0.30% DL-methionine supplemented diet reversed partially the egg laying inhibited by the diet with 0.30% DL-ethionine alone. No inhibitory effect on egg laying was observed for the diet supplemented with 0.30% DL-methionine alone. In marked contrast to the decreased activity of L-glycerol 3-phosphate dehydrogenase and malate dehydrogenase, significantly increased activity of lactate dehydrogenase was obtained for quail fed the DL-ethionine, and the DL-ethionine plus the DL-methionine supplemented diet, respectively. No marked changes in activities of these three dehydrogenases were obtained for quail fed the diet supplemented with DL-methionine alone. Although decreased activity was observed for all of the four NADPH-producing enzymes in quail fed the diet supplemented with DL-ethionine alone, the DL-ethionine plus DL-methionine, the smallest decrease was obtained for NADP-isocitrate dehydrogenase. The diet supplemented with DL-methionine alone induced markedly the respective activity of malic enzyme and  glucose 6-phosphate dehydrogenase. These results indicate a relatively important  function of NADP-isocitrate dehydrogenase for NADPH-production even under DL-ethionine toxicity and suggest complicated relationships between egg production and activities of enzymes associated with carbohydrate and lipid metabolism in quail liver.", "contents": "Effect of dietary DL-ethionine and/or DL-methionine on egg laying and activities of some cytoplasmic NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica. The effect of dietary DL-ethionine and/or DL-methionine on egg laying, and activities of some NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica was investigated. A 0.30% DL-ethionine plus 0.30% DL-methionine supplemented diet reversed partially the egg laying inhibited by the diet with 0.30% DL-ethionine alone. No inhibitory effect on egg laying was observed for the diet supplemented with 0.30% DL-methionine alone. In marked contrast to the decreased activity of L-glycerol 3-phosphate dehydrogenase and malate dehydrogenase, significantly increased activity of lactate dehydrogenase was obtained for quail fed the DL-ethionine, and the DL-ethionine plus the DL-methionine supplemented diet, respectively. No marked changes in activities of these three dehydrogenases were obtained for quail fed the diet supplemented with DL-methionine alone. Although decreased activity was observed for all of the four NADPH-producing enzymes in quail fed the diet supplemented with DL-ethionine alone, the DL-ethionine plus DL-methionine, the smallest decrease was obtained for NADP-isocitrate dehydrogenase. The diet supplemented with DL-methionine alone induced markedly the respective activity of malic enzyme and  glucose 6-phosphate dehydrogenase. These results indicate a relatively important  function of NADP-isocitrate dehydrogenase for NADPH-production even under DL-ethionine toxicity and suggest complicated relationships between egg production and activities of enzymes associated with carbohydrate and lipid metabolism in quail liver."}
{"id": "PMID:16101", "title": "Stimulation of neutral amino acid transport by fructose in epithelial cells isolated from rat intestine.", "content": "Interest in the nutritional and physiological implications of the high dietary intakes of fructose from sucrose and isomerized corn sweeteners has directed attention to the specific metabolic properties of this monosaccharide. Epithelial cells isolated from the small  intestine of Wistar rats fed a stock diet showed 24% to 57% higher transport of 1 mM leucine, isoleucine, valine, alanine, phenylalanine tryptophan and histidine in the presence of 10 mM fructose than in its absence. In contrast, 10mM glucose generally inhibited the transport of these amino acids and 10mM sorbose had no effect on leucine transport. Fructose failed to consistently stimulate the transport of basic amino acids and generally inhibited the transport of glucose and galactose, indicating that the stimulation was relatively specific for neutral amino acids. Cells preloaded with fructose optimally stimulated leucine transport in the absence of extracellular fructose. Ouabain and dinitrophenol inhibited the stimulation of leucine transport by intracellular fructose after 2 minutes. A stimulation mediated by an exchange transport mechanism was rejected on  the basis of the failure of 1 mM neutral amino acids either  to inhibit the transport of 10 mM fructose or to accelerate the movement of fructose out of fructose-loaded cells. Although the mechanism remains unknown, these results demonstrate a specific effect of fructose at the intestinal level that produces a stimulation of neutral amino acid transport.", "contents": "Stimulation of neutral amino acid transport by fructose in epithelial cells isolated from rat intestine. Interest in the nutritional and physiological implications of the high dietary intakes of fructose from sucrose and isomerized corn sweeteners has directed attention to the specific metabolic properties of this monosaccharide. Epithelial cells isolated from the small  intestine of Wistar rats fed a stock diet showed 24% to 57% higher transport of 1 mM leucine, isoleucine, valine, alanine, phenylalanine tryptophan and histidine in the presence of 10 mM fructose than in its absence. In contrast, 10mM glucose generally inhibited the transport of these amino acids and 10mM sorbose had no effect on leucine transport. Fructose failed to consistently stimulate the transport of basic amino acids and generally inhibited the transport of glucose and galactose, indicating that the stimulation was relatively specific for neutral amino acids. Cells preloaded with fructose optimally stimulated leucine transport in the absence of extracellular fructose. Ouabain and dinitrophenol inhibited the stimulation of leucine transport by intracellular fructose after 2 minutes. A stimulation mediated by an exchange transport mechanism was rejected on  the basis of the failure of 1 mM neutral amino acids either  to inhibit the transport of 10 mM fructose or to accelerate the movement of fructose out of fructose-loaded cells. Although the mechanism remains unknown, these results demonstrate a specific effect of fructose at the intestinal level that produces a stimulation of neutral amino acid transport."}
{"id": "PMID:16102", "title": "Influence of dietary lipid on lipogenic enzyme activities in coho salmon, Oncorhynchus kisutch (Walbaum).", "content": "Coho salmon (Oncorhynchus kisutch), 8 to 18 months of age, were maintained in culture tanks and were fed three semipurified diets. The diets contained 40% of energy from protein and 11.5%, 23%, or 46% of energy from lipid. The body weight gain and food conversion factors were similar among groups of fish fed the diets in each of the three experiments. Wet weight of mesenteric adipose tissue increased with increased amount of lipid in the diet; however, epaxial muscle lipid content was not influenced by the lipid content of the diet. Several hepatic and adipose tissue lipogenic enzymes (fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-isocitrate dehydrogenase) were assayed. These lipogenic enzymes exhibited high activities in liver and relatively low concentration in adipose tissue of the fish. The activities of all the hepatic lipogenic enzymes assayed, except for NADP-isocitrate dehydrogenase, were depressed as the level of lipid in the diet was increased; however, the activities of these enzymes in mesenteric adipose tissue were not influenced by the diets fed. The results of this study indicate that dietary lipid depresses hepatic lipogenic enzyme activities and that the liver may be a more important site for fatty acid synthesis than is adipose tissue in coho salmon.", "contents": "Influence of dietary lipid on lipogenic enzyme activities in coho salmon, Oncorhynchus kisutch (Walbaum). Coho salmon (Oncorhynchus kisutch), 8 to 18 months of age, were maintained in culture tanks and were fed three semipurified diets. The diets contained 40% of energy from protein and 11.5%, 23%, or 46% of energy from lipid. The body weight gain and food conversion factors were similar among groups of fish fed the diets in each of the three experiments. Wet weight of mesenteric adipose tissue increased with increased amount of lipid in the diet; however, epaxial muscle lipid content was not influenced by the lipid content of the diet. Several hepatic and adipose tissue lipogenic enzymes (fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-isocitrate dehydrogenase) were assayed. These lipogenic enzymes exhibited high activities in liver and relatively low concentration in adipose tissue of the fish. The activities of all the hepatic lipogenic enzymes assayed, except for NADP-isocitrate dehydrogenase, were depressed as the level of lipid in the diet was increased; however, the activities of these enzymes in mesenteric adipose tissue were not influenced by the diets fed. The results of this study indicate that dietary lipid depresses hepatic lipogenic enzyme activities and that the liver may be a more important site for fatty acid synthesis than is adipose tissue in coho salmon."}
{"id": "PMID:16103", "title": "The immediate nucleotide precursor, guanosine triphosphate, in the riboflavin biosynthetic pathway.", "content": "In the present paper, the nucleotide precursor of riboflavin was investigated by experiments with labeled purines using non-growing cells of Eremothecium ashybii. The added purines, at 10(-4) M, were effectively incorporated into riboflavin at an early stage of riboflavin biosynthesis under the experimental conditions. In particular, both labeled xanthine and labeled guanine were specifically transported to guanosine nucleotides, GMP, GDP, GDP-Mannose and GTP, in the course of the riboflavin biosynthesis. A comparison of specific activities of labeled guanosine nucleotides and labeled riboflavin indicated that the nucleotide precursor of riboflavin is guanosine triphosphate. From the results obtained, a biosynthetic pathway of riboflavin is proposed under \"DISCUSSION.\"", "contents": "The immediate nucleotide precursor, guanosine triphosphate, in the riboflavin biosynthetic pathway. In the present paper, the nucleotide precursor of riboflavin was investigated by experiments with labeled purines using non-growing cells of Eremothecium ashybii. The added purines, at 10(-4) M, were effectively incorporated into riboflavin at an early stage of riboflavin biosynthesis under the experimental conditions. In particular, both labeled xanthine and labeled guanine were specifically transported to guanosine nucleotides, GMP, GDP, GDP-Mannose and GTP, in the course of the riboflavin biosynthesis. A comparison of specific activities of labeled guanosine nucleotides and labeled riboflavin indicated that the nucleotide precursor of riboflavin is guanosine triphosphate. From the results obtained, a biosynthetic pathway of riboflavin is proposed under \"DISCUSSION.\""}
{"id": "PMID:16104", "title": "Reconstitution of T-cell function in severe combined immunodeficiency disease following transplantation of early embryonic liver cells.", "content": "In a 51/2-month-old male infant with adenosine deaminase-positive severe combined immunodeficiency disease, who had no suitable bone marrow donor, immunologic reconstitution was attempted with lymphoid cells obtained from the liver of a 4- to 5-week-old-male human embryo. A mild graft-versus-host reaction began three weeks later. T-cells, which were absent prior to infusion of hepatic lymphoid cells, rose to a maximum of 554/mm3 at 16 weeks post transplantation. A normal lymphocyte response to pokeweek mitogen was not present until 25 to 30 weeks and to allogeneic cells until 39 weeks. Postive in vitro lymphocyte responses to Candida albicans were found repeatedly after 52 weeks. Twenty months following transplantation the patient is free of clinical infection, although he requires regular injections of gamma globulin.", "contents": "Reconstitution of T-cell function in severe combined immunodeficiency disease following transplantation of early embryonic liver cells. In a 51/2-month-old male infant with adenosine deaminase-positive severe combined immunodeficiency disease, who had no suitable bone marrow donor, immunologic reconstitution was attempted with lymphoid cells obtained from the liver of a 4- to 5-week-old-male human embryo. A mild graft-versus-host reaction began three weeks later. T-cells, which were absent prior to infusion of hepatic lymphoid cells, rose to a maximum of 554/mm3 at 16 weeks post transplantation. A normal lymphocyte response to pokeweek mitogen was not present until 25 to 30 weeks and to allogeneic cells until 39 weeks. Postive in vitro lymphocyte responses to Candida albicans were found repeatedly after 52 weeks. Twenty months following transplantation the patient is free of clinical infection, although he requires regular injections of gamma globulin."}
{"id": "PMID:16105", "title": "Peritoneal dialysis for severe methyprylon intoxication.", "content": "The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication.", "contents": "Peritoneal dialysis for severe methyprylon intoxication. The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication."}
{"id": "PMID:16106", "title": "Development of Haemonchus contortus in vitro and the stimulus from the host.", "content": "Infective larvae of Haemonchus contortus which have been exposed for about 9 hr to relatively high partial pressures of carbon dioxide at near-neutral pH, as they might be in the rumen, develop slowly to the fourth stage or not at all. But following this treatment, exposure to lower partial pressures of carbon dioxide and higher concentrations of hydrogen ions, such as might be encountered in the abomasal mucosa, brings about development at a rate comparable with that in the sheep.", "contents": "Development of Haemonchus contortus in vitro and the stimulus from the host. Infective larvae of Haemonchus contortus which have been exposed for about 9 hr to relatively high partial pressures of carbon dioxide at near-neutral pH, as they might be in the rumen, develop slowly to the fourth stage or not at all. But following this treatment, exposure to lower partial pressures of carbon dioxide and higher concentrations of hydrogen ions, such as might be encountered in the abomasal mucosa, brings about development at a rate comparable with that in the sheep."}
{"id": "PMID:16111", "title": "In vitro adsortpion of acetaminophen onto activated charcoal.", "content": "In vitro experiments supported in vivo evidence that activated charcoal is effective in adsorbing acetaminophen. In the physiologic pH range, adsorption was rapid and pH independent. Adsorption, however, was dependent upon the quantity of activated charcoal employed, becoming more complete as the quantity of activated charcoal was increased.", "contents": "In vitro adsortpion of acetaminophen onto activated charcoal. In vitro experiments supported in vivo evidence that activated charcoal is effective in adsorbing acetaminophen. In the physiologic pH range, adsorption was rapid and pH independent. Adsorption, however, was dependent upon the quantity of activated charcoal employed, becoming more complete as the quantity of activated charcoal was increased."}
{"id": "PMID:16112", "title": "Conformational studies of antiradiation agents by NMR: cysteamine and its derivatives.", "content": "The conformations of cysteamine, thiazolidine, and thiazolidine-4-carboxylic acid were determined in aqueous solutions using NMR spectroscopy. At physiological pH, the population ratio of gauche- and trans-conformers was 3:1. The gauche-rotamer is probably responsible for the antiradiation activity and acts through metal chelation involving sulfur and nitrogen atoms. The puckering of the thiazolidine ring was calculated using NMR coupling constants. The observed results were compared with those obtained in the solid state using X-ray diffraction.", "contents": "Conformational studies of antiradiation agents by NMR: cysteamine and its derivatives. The conformations of cysteamine, thiazolidine, and thiazolidine-4-carboxylic acid were determined in aqueous solutions using NMR spectroscopy. At physiological pH, the population ratio of gauche- and trans-conformers was 3:1. The gauche-rotamer is probably responsible for the antiradiation activity and acts through metal chelation involving sulfur and nitrogen atoms. The puckering of the thiazolidine ring was calculated using NMR coupling constants. The observed results were compared with those obtained in the solid state using X-ray diffraction."}
{"id": "PMID:16113", "title": "Solubility studies of silver sulfadiazine.", "content": "The solubility of silver sulfadiazine as a function of pH was determined in nitric acid-potassium nitrate buffer for pH 2-3 and in 2-(N-morpholino)ethanesulfonic acid buffer for pH 6-7. As the salt of a weak organic acid, silver sulfadiazine exhibits the anticipated increase in solubility with an increasing hydrogen-ion concentration. Measurement of the silver-ion concentration was carried out using a silver-ion selective electrode. The methods of known subtraction and known addition were utilized to measure the total concentration of the silver ion in solution. Evidence was obtained to indicate that the salt is completely ionized in aqueous solution.", "contents": "Solubility studies of silver sulfadiazine. The solubility of silver sulfadiazine as a function of pH was determined in nitric acid-potassium nitrate buffer for pH 2-3 and in 2-(N-morpholino)ethanesulfonic acid buffer for pH 6-7. As the salt of a weak organic acid, silver sulfadiazine exhibits the anticipated increase in solubility with an increasing hydrogen-ion concentration. Measurement of the silver-ion concentration was carried out using a silver-ion selective electrode. The methods of known subtraction and known addition were utilized to measure the total concentration of the silver ion in solution. Evidence was obtained to indicate that the salt is completely ionized in aqueous solution."}
{"id": "PMID:16114", "title": "Metal-ion interaction with penicillins: kinetics of complexation of nickel(II).", "content": "The kinetics of complexation of nickel(II) with some penicillins and related compounds show that the zwitterionic form of the ligand has very low reactivity compared to the anionic form. The resolved rate constants are interpreted in terms of binding to the ring nitrogen and carboxyl group and not to the side chain.", "contents": "Metal-ion interaction with penicillins: kinetics of complexation of nickel(II). The kinetics of complexation of nickel(II) with some penicillins and related compounds show that the zwitterionic form of the ligand has very low reactivity compared to the anionic form. The resolved rate constants are interpreted in terms of binding to the ring nitrogen and carboxyl group and not to the side chain."}
{"id": "PMID:16116", "title": "Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines II: oxazepam and diazepam.", "content": "The hydrolysis kinetics of oxazepam and diazepam leading to a benzophenone product and a glycine derivative were quantified from pH 1 to 11. For oxazepam, two intermediates were isolated and identified, indicating a parallel consecutive reaction mechanism. The hydrolysis occurred uncatalyzed and demonstrated acid-base catalysis for both reaction steps. One intermediate was observed by TLC for diazepam hydrolysis. This intermediate, resulting from breakage of the azomethine linkage, was different than the major intermediate isolated for oxazepam hydrolytic degradation (amide hydrolysis preferred). Stability parameters involving rate constant-temperature dependence are reported.", "contents": "Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines II: oxazepam and diazepam. The hydrolysis kinetics of oxazepam and diazepam leading to a benzophenone product and a glycine derivative were quantified from pH 1 to 11. For oxazepam, two intermediates were isolated and identified, indicating a parallel consecutive reaction mechanism. The hydrolysis occurred uncatalyzed and demonstrated acid-base catalysis for both reaction steps. One intermediate was observed by TLC for diazepam hydrolysis. This intermediate, resulting from breakage of the azomethine linkage, was different than the major intermediate isolated for oxazepam hydrolytic degradation (amide hydrolysis preferred). Stability parameters involving rate constant-temperature dependence are reported."}
{"id": "PMID:16115", "title": "Mechanism of histamine binding II: effect of alkali metal and alkaline earth cations on histamine binding to peptide H.", "content": "The association constants of histamine with Mg2+, Ca2+, Sr2+, and Ba2+ were determined in buffer solutions at constant pH using an ion selective electrode. These cations enabled histamine to bind to peptide H. A minimum cation binding concentration was required for histamine binding. A linear relationship existed between the minimum cation binding concentration and the log of the equilibrium constant for the histamine-cation complexes, indicating that the specificity of the alkaline earth cations in promoting histamine binding was due to the difference in their ability to complex with histamine. The monovalent cations, Nat, Kt, and Cst inhibited histamine binding to peptide H, with the extent of inhibition dependent on cation concentration. An ion-exchange mechanism or a conformation change in the peptide may account for the inhibition.", "contents": "Mechanism of histamine binding II: effect of alkali metal and alkaline earth cations on histamine binding to peptide H. The association constants of histamine with Mg2+, Ca2+, Sr2+, and Ba2+ were determined in buffer solutions at constant pH using an ion selective electrode. These cations enabled histamine to bind to peptide H. A minimum cation binding concentration was required for histamine binding. A linear relationship existed between the minimum cation binding concentration and the log of the equilibrium constant for the histamine-cation complexes, indicating that the specificity of the alkaline earth cations in promoting histamine binding was due to the difference in their ability to complex with histamine. The monovalent cations, Nat, Kt, and Cst inhibited histamine binding to peptide H, with the extent of inhibition dependent on cation concentration. An ion-exchange mechanism or a conformation change in the peptide may account for the inhibition."}
{"id": "PMID:16117", "title": "Motor innervation of the smooth muscle of the rat seminal vesicle.", "content": "Frequency-related isovolumetric contractions of the rat seminal vesicle elicited with transmural electrical stimulation were blocked by tetrodotoxin but unaffected by hexamethonium. The postganglionic motor innervation of the rat seminal vesicle is purely excitatory and contains both an adrenergic and a cholinergic component which are excited simultaneously during transmural stimulation. Contractions elicited by adrenergic nerve stimulation were mediated by norepinephrine acting via alpha adrenoceptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous norepinephrine were antagonized by phentolamine and potentiated by cocaine, 2) pretreatment of animals with reserpine or 6-hydroxydopamine produced a marked depletion of tissue norepinephrine concentration and reduced the responses to transmural stimulation to a level which resembled that of untreated organs in the presence of phentolamine, 3) the residual responses of vesicles from pretreated rats were not modified by phentolamine or cocaine, and 4) responses to tyramine in untreated organs were antagonized by phentolamine but not by cocaine and were observed in organs from reserpine-pretreated rats only after repletion with exogenous norepinephrine. Responses elicited by cholinergic nerve stimulation were mediated by acetylcholine through muscarinic receptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous acetylcholine were antagonized by atropine, 2) the residual responses to transmural stimulation of vesicles from animals pretreated with reserpine of 6-hydroxydopamine were nearly abolished by atropine and 3) physostigmine potentiated and prolonged the responses of organs from untreated and reserpine-pretreatd animals to transmural stimulation; these effects of physostigmine were abolished by atropine.", "contents": "Motor innervation of the smooth muscle of the rat seminal vesicle. Frequency-related isovolumetric contractions of the rat seminal vesicle elicited with transmural electrical stimulation were blocked by tetrodotoxin but unaffected by hexamethonium. The postganglionic motor innervation of the rat seminal vesicle is purely excitatory and contains both an adrenergic and a cholinergic component which are excited simultaneously during transmural stimulation. Contractions elicited by adrenergic nerve stimulation were mediated by norepinephrine acting via alpha adrenoceptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous norepinephrine were antagonized by phentolamine and potentiated by cocaine, 2) pretreatment of animals with reserpine or 6-hydroxydopamine produced a marked depletion of tissue norepinephrine concentration and reduced the responses to transmural stimulation to a level which resembled that of untreated organs in the presence of phentolamine, 3) the residual responses of vesicles from pretreated rats were not modified by phentolamine or cocaine, and 4) responses to tyramine in untreated organs were antagonized by phentolamine but not by cocaine and were observed in organs from reserpine-pretreated rats only after repletion with exogenous norepinephrine. Responses elicited by cholinergic nerve stimulation were mediated by acetylcholine through muscarinic receptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous acetylcholine were antagonized by atropine, 2) the residual responses to transmural stimulation of vesicles from animals pretreated with reserpine of 6-hydroxydopamine were nearly abolished by atropine and 3) physostigmine potentiated and prolonged the responses of organs from untreated and reserpine-pretreatd animals to transmural stimulation; these effects of physostigmine were abolished by atropine."}
{"id": "PMID:16118", "title": "Organ culture of rat superior cervical ganglia.", "content": "The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine.", "contents": "Organ culture of rat superior cervical ganglia. The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine."}
{"id": "PMID:16119", "title": "Effects of ethosuximide on transmission of repetitive impulses and apparent rates of transmitter turnover in the spinal monosynaptic pathway.", "content": "The effects of ethosuximide on spinal monosynaptic transmission were studied in cats. The drug in doses of 200 or 400 mg/kg deepened the decline of monosynaptic response amplitude evoked by trains of 10 stimuli to a motor nerve at 2, 5 or 10 Hz, without affecting the transmission of single isolated impulses. The patterns of decline were analyzed under the assumption that they reflect a partial depletion of the apparent transmitter stores in the presynaptic terminals, each incoming volley releasing a constant fraction of the store while a constant fraction of the instant size of the depleted part is being replenished per second. Ethosuximide increased the fractional release without a consistent effect on the fractional rate of replenishment. It is suggested that the resulting more rapid and more profound depletion of the apparent transmitter store could account for the observed preferential depression of repetitive transmission in the spinal monosynaptic pathway by this drug.", "contents": "Effects of ethosuximide on transmission of repetitive impulses and apparent rates of transmitter turnover in the spinal monosynaptic pathway. The effects of ethosuximide on spinal monosynaptic transmission were studied in cats. The drug in doses of 200 or 400 mg/kg deepened the decline of monosynaptic response amplitude evoked by trains of 10 stimuli to a motor nerve at 2, 5 or 10 Hz, without affecting the transmission of single isolated impulses. The patterns of decline were analyzed under the assumption that they reflect a partial depletion of the apparent transmitter stores in the presynaptic terminals, each incoming volley releasing a constant fraction of the store while a constant fraction of the instant size of the depleted part is being replenished per second. Ethosuximide increased the fractional release without a consistent effect on the fractional rate of replenishment. It is suggested that the resulting more rapid and more profound depletion of the apparent transmitter store could account for the observed preferential depression of repetitive transmission in the spinal monosynaptic pathway by this drug."}
{"id": "PMID:16120", "title": "The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord.", "content": "Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo.", "contents": "The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord. Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo."}
{"id": "PMID:16121", "title": "Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial.", "content": "The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches.", "contents": "Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial. The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches."}
{"id": "PMID:16122", "title": "Specific enhancement of norepinephrine-induced contraction in rat veins after beta adrenergic antagonists.", "content": "Propranolol markedly increased the norepinephrine-induced maximal force in circular smooth muscle of the rat portal, mesenteric, renal and, to a lesser extent, femoral veins without affecting aortic or mesenteric artery responses to norepinephrine. Furthermore, two other beta receptor antagonists, practolol and N-isopropylmethoxamine, specifically enhanced maximal venous responses to norepinephrine. Contractions to norepinephrine, but not to serotonin, were increased by propranolol only in veins, even after the vasodilator, papaverine. The ability of propranolol to enhance norepinephrine-induced contraction in these rat veins paralleled the effectiveness of isoproterenol to relax such tissues. In addition, beta receptor antagonists enhanced the response of veins to the field stimulated release of norepinephrine from sympathetic nerves. These data support the conclusion that beta adrenergic stimulation modulates norepinephrine-induced constriction in certain rat veins but not in the aorta or mesenteric artery.", "contents": "Specific enhancement of norepinephrine-induced contraction in rat veins after beta adrenergic antagonists. Propranolol markedly increased the norepinephrine-induced maximal force in circular smooth muscle of the rat portal, mesenteric, renal and, to a lesser extent, femoral veins without affecting aortic or mesenteric artery responses to norepinephrine. Furthermore, two other beta receptor antagonists, practolol and N-isopropylmethoxamine, specifically enhanced maximal venous responses to norepinephrine. Contractions to norepinephrine, but not to serotonin, were increased by propranolol only in veins, even after the vasodilator, papaverine. The ability of propranolol to enhance norepinephrine-induced contraction in these rat veins paralleled the effectiveness of isoproterenol to relax such tissues. In addition, beta receptor antagonists enhanced the response of veins to the field stimulated release of norepinephrine from sympathetic nerves. These data support the conclusion that beta adrenergic stimulation modulates norepinephrine-induced constriction in certain rat veins but not in the aorta or mesenteric artery."}
{"id": "PMID:16123", "title": "Urinary carbon dioxide tension in lithium carbonate-treated patients.", "content": "Renal acidification was studied in 12 lithium carbonate-treated psychiatric patients. The urinary Pco2 response to oral sodium bicarbonate loading, a qualitative index of distal hydrogen ion secretion, was evaluated in all patients and the results were compared with those obtained in 10 control subjects. The average maximal urine to arterial blood Pco2 difference (U-A Pco2) in the psychiatric patients [26 +/- 3 (S.E.) mm Hg] was significantly lower (P less than .001) than that of control subjects (51 +/- 3 mm Hg) and only three patients had values greater than 31 mm Hg (2 S.D. below the mean control value). Eight of these patients were also evaluated with NH4CL acid loading. Seven of eight patients had a minimal urine pH less than 5.30 after NH4CL administration; only one of the seven had a normal U-APco2 after bicarbonate loading. Three patients were evaluated prior to treatment and after 2 weeks of lithium administration. Pretreatment U-APco2 values were normal. After therapy the values were lower in all three patients becoming definitely abnormal in two. The present investigation, in concert with previous animal studies, demonstrates that chronic lithium carbonate therapy in man may result in decreased U-A Pco2.", "contents": "Urinary carbon dioxide tension in lithium carbonate-treated patients. Renal acidification was studied in 12 lithium carbonate-treated psychiatric patients. The urinary Pco2 response to oral sodium bicarbonate loading, a qualitative index of distal hydrogen ion secretion, was evaluated in all patients and the results were compared with those obtained in 10 control subjects. The average maximal urine to arterial blood Pco2 difference (U-A Pco2) in the psychiatric patients [26 +/- 3 (S.E.) mm Hg] was significantly lower (P less than .001) than that of control subjects (51 +/- 3 mm Hg) and only three patients had values greater than 31 mm Hg (2 S.D. below the mean control value). Eight of these patients were also evaluated with NH4CL acid loading. Seven of eight patients had a minimal urine pH less than 5.30 after NH4CL administration; only one of the seven had a normal U-APco2 after bicarbonate loading. Three patients were evaluated prior to treatment and after 2 weeks of lithium administration. Pretreatment U-APco2 values were normal. After therapy the values were lower in all three patients becoming definitely abnormal in two. The present investigation, in concert with previous animal studies, demonstrates that chronic lithium carbonate therapy in man may result in decreased U-A Pco2."}
{"id": "PMID:16124", "title": "The development of some metabolic responses to hypoxia in the foetal sheep.", "content": "1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life.", "contents": "The development of some metabolic responses to hypoxia in the foetal sheep. 1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life."}
{"id": "PMID:16125", "title": "Possible explanations for the differences in secretory characteristics between conjugated and free bile acids.", "content": "1. The hepatic extraction fraction and maximum excretory rate of conjugated cholate are greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of un-ionized cholic acid (pKa 5-5) compared to that of taurocholic acid (pKa 2) has been investigated by varying the pH of bile by secretin or acetazolamide administration in the anaesthetized dog. 2. The mean biliary pH during free cholate excretion in the control state in twenty-three experiments was 7-5 (at which approximately 1% of cholate is un-ionized). Three to fourfold changes in the hydrogen ion activity of bile (which resulted in changes of the same magnitude in the percentage of un-ionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. It is concluded that back-diffusion of un-ionized cholic acid in the bile ducts is not an important determinant of the secretory performance of free cholate. 3. The bile flow rate associated with mainly free cholate excretion is much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appears to arise largely by means that are independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free free cholate (calculated directly) was only slightly greater than that of bile containing mainly taurocholate (obtained by extrapolation) at the same total cholate concentration. 4. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about one fifth of the maximum rate attainable; at the peak rate taurocholate is almost completely removed in the first passage of blood through the liver.", "contents": "Possible explanations for the differences in secretory characteristics between conjugated and free bile acids. 1. The hepatic extraction fraction and maximum excretory rate of conjugated cholate are greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of un-ionized cholic acid (pKa 5-5) compared to that of taurocholic acid (pKa 2) has been investigated by varying the pH of bile by secretin or acetazolamide administration in the anaesthetized dog. 2. The mean biliary pH during free cholate excretion in the control state in twenty-three experiments was 7-5 (at which approximately 1% of cholate is un-ionized). Three to fourfold changes in the hydrogen ion activity of bile (which resulted in changes of the same magnitude in the percentage of un-ionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. It is concluded that back-diffusion of un-ionized cholic acid in the bile ducts is not an important determinant of the secretory performance of free cholate. 3. The bile flow rate associated with mainly free cholate excretion is much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appears to arise largely by means that are independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free free cholate (calculated directly) was only slightly greater than that of bile containing mainly taurocholate (obtained by extrapolation) at the same total cholate concentration. 4. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about one fifth of the maximum rate attainable; at the peak rate taurocholate is almost completely removed in the first passage of blood through the liver."}
{"id": "PMID:16126", "title": "The effect of calcium injection on the intracellular sodium and pH of snail neurones.", "content": "1. Ion-sensitive glass micro-electrodes were used to measure the intracellular pH (pHi) and the intracellular sodium ion concentration, [Na+]i, in identified Helix aspersa neurones. 2. The injection of small volumes of 0-1 McaCl2, which increased the membrane potential by 10-15 mV for 1-2 min, had little or no effect on [Na+]i. Increases of up to 1 mM in [Na+]i could be reversibly induced by larger injections. 3. Calcium injection caused an immediate decrease in pHi, which appeared to be directly proportional to the amount of calcium injected. Injections causing hyperpolarizations of 10-20 mV which recovered in 2-5 min caused pHi decreases of 0-04-0-15 units. After each of these injections both pHi and the membrane potential recovered exponentially but with different time constants. 4. The injection of calcium at a low rate could decrease pHi without affecting the membrane potential. 5. Neither membrane potential nor pHi were affected by the injection of small volumes of 0-1 M-MgCl2, Injection of CoCl2 produced a large transient decrease in pHi but no significant change in membrane potential. 6. Exposure of the cell to saline equilibrated with 2-5% CO2 greatly reduced the pHi decrease caused by calcium injection but had only small effects on the membrane potential response. 7. It is concluded that most of the injected calcium is exchanged for protons inside the cell.", "contents": "The effect of calcium injection on the intracellular sodium and pH of snail neurones. 1. Ion-sensitive glass micro-electrodes were used to measure the intracellular pH (pHi) and the intracellular sodium ion concentration, [Na+]i, in identified Helix aspersa neurones. 2. The injection of small volumes of 0-1 McaCl2, which increased the membrane potential by 10-15 mV for 1-2 min, had little or no effect on [Na+]i. Increases of up to 1 mM in [Na+]i could be reversibly induced by larger injections. 3. Calcium injection caused an immediate decrease in pHi, which appeared to be directly proportional to the amount of calcium injected. Injections causing hyperpolarizations of 10-20 mV which recovered in 2-5 min caused pHi decreases of 0-04-0-15 units. After each of these injections both pHi and the membrane potential recovered exponentially but with different time constants. 4. The injection of calcium at a low rate could decrease pHi without affecting the membrane potential. 5. Neither membrane potential nor pHi were affected by the injection of small volumes of 0-1 M-MgCl2, Injection of CoCl2 produced a large transient decrease in pHi but no significant change in membrane potential. 6. Exposure of the cell to saline equilibrated with 2-5% CO2 greatly reduced the pHi decrease caused by calcium injection but had only small effects on the membrane potential response. 7. It is concluded that most of the injected calcium is exchanged for protons inside the cell."}
{"id": "PMID:16129", "title": "Facilitation of transmitter secretion from toad motor nerve terminals during brief trains of action potentials.", "content": "1. End-plate potentials produced by brief trains of action potentials (5-7 at 50-100 Hz) were recorded at toad sciatic-sartorius neuromuscular junctions. When transmitter secretion was depressed in solutions containing magnesium, the increase in amplitude (growth pattern) of successive end-plate-potentials was greater than could be accounted for by arithmetic summation of facilitation (arithmetic model) as proposed by Mallart & Martin (1967). 3. With e.p.p.s of normal quantral content or in solutions in which the calcium concentration was lowered, growth patterns were occasionally reasonably close to those predicted by the arithmetic model but there was always some degree of disparity. 4. A simple, two-step, kinetic model is described which is more consistent with the varied growth patterns of end-plate potentials that have been recorded. The model can predict growth patterns of e.p.p.s with high or low quantal content.", "contents": "Facilitation of transmitter secretion from toad motor nerve terminals during brief trains of action potentials. 1. End-plate potentials produced by brief trains of action potentials (5-7 at 50-100 Hz) were recorded at toad sciatic-sartorius neuromuscular junctions. When transmitter secretion was depressed in solutions containing magnesium, the increase in amplitude (growth pattern) of successive end-plate-potentials was greater than could be accounted for by arithmetic summation of facilitation (arithmetic model) as proposed by Mallart & Martin (1967). 3. With e.p.p.s of normal quantral content or in solutions in which the calcium concentration was lowered, growth patterns were occasionally reasonably close to those predicted by the arithmetic model but there was always some degree of disparity. 4. A simple, two-step, kinetic model is described which is more consistent with the varied growth patterns of end-plate potentials that have been recorded. The model can predict growth patterns of e.p.p.s with high or low quantal content."}
{"id": "PMID:16128", "title": "Extracellular potassium and trasmitter release at the giant synapse of squid.", "content": "1. The effects of changes in extracellular K concentration, [K]0, on synaptic transmission were studied at the squid giant synapse with intracellular recording from the presynaptic terminal and post-synaptic axon. 2. The amplitudes of both the presynaptic spike and the e.p.s.p. varied inversely with [K]0. On the average, a 10 mV change in spike height was accompanied by a 3-1 mV change in e.p.s.p. amplitude. 3. The amplitude of the presynaptic spike after-hyperpolarization (AH) varied inversely with [K]0. On the average, increasing [K]0 resulted in a 20% change in e.p.s.p. amplitude per mV change in presynaptic spike AH. 4. Repetitive antidromic stimulation of the post-synaptic giant axon resulted in an exponential decline in the post-synaptic spike AH, a depolarization of the presynaptic membrane potential and a reduction in the AHs of presynaptic spikes. This suggests that the K which accumulates in the extracellular spaces around the post-synaptic axon also affects the presynaptic terminal. 5. Repetitive antidromic stimulation of the post-synaptic axon resulted in a reduction in the amplitude of e.p.s.p.s. elicted by stimulation of the presynaptic axon. The reduction in e.p.s.p. amplitude relative to the change in presynaptic spike AH was quantitatively close to the change produced by increasing [K]0, suggesting that the reduction in e.p.s.p. amplitude is due to the accumulation of extracellular K at the presynaptic terminal. 6. Repetitive stimulation of the presynaptic axon reduced the amplitudes of the e.p.s.p. and the presynaptic spike AH. On the average, a 1 mV change in presynaptic spike AH was accompanied by a 204% change in e.p.s.p. amplitude, suggesting that K accumulation may only contribute to a small extent, under these conditions, to the depression of transmitter release.", "contents": "Extracellular potassium and trasmitter release at the giant synapse of squid. 1. The effects of changes in extracellular K concentration, [K]0, on synaptic transmission were studied at the squid giant synapse with intracellular recording from the presynaptic terminal and post-synaptic axon. 2. The amplitudes of both the presynaptic spike and the e.p.s.p. varied inversely with [K]0. On the average, a 10 mV change in spike height was accompanied by a 3-1 mV change in e.p.s.p. amplitude. 3. The amplitude of the presynaptic spike after-hyperpolarization (AH) varied inversely with [K]0. On the average, increasing [K]0 resulted in a 20% change in e.p.s.p. amplitude per mV change in presynaptic spike AH. 4. Repetitive antidromic stimulation of the post-synaptic giant axon resulted in an exponential decline in the post-synaptic spike AH, a depolarization of the presynaptic membrane potential and a reduction in the AHs of presynaptic spikes. This suggests that the K which accumulates in the extracellular spaces around the post-synaptic axon also affects the presynaptic terminal. 5. Repetitive antidromic stimulation of the post-synaptic axon resulted in a reduction in the amplitude of e.p.s.p.s. elicted by stimulation of the presynaptic axon. The reduction in e.p.s.p. amplitude relative to the change in presynaptic spike AH was quantitatively close to the change produced by increasing [K]0, suggesting that the reduction in e.p.s.p. amplitude is due to the accumulation of extracellular K at the presynaptic terminal. 6. Repetitive stimulation of the presynaptic axon reduced the amplitudes of the e.p.s.p. and the presynaptic spike AH. On the average, a 1 mV change in presynaptic spike AH was accompanied by a 204% change in e.p.s.p. amplitude, suggesting that K accumulation may only contribute to a small extent, under these conditions, to the depression of transmitter release."}
{"id": "PMID:16130", "title": "[Arteriographic appearances seen in the course of development of the lesions of polyarteritis nodosa (author's transl)].", "content": "Three cases of polyarteritis nodosa (P.A.N.) studied by abdominal arteriography with a follow-up examination between the 6th and 9th month are reported. In the first case, the initial arteriogram showed only the appearances of endarteritis. The second arteriogram, 9 months later, following a worsening of general condition, revealed diffuse aneurysms in the abdomen. In the second patient, who had multiple aneurysms at the time of the initial examination, arteriography agter 6 months following a new episode of the disease with an acute abdominal syndrome and collapse revealed, alongside the multiplication of the aneurysms with rupture of one of them, the disappearance of some ectasias with the obliteration of certain arteries. In the third patient, the follow-up arteriogram after treatment showed disappearance of the renal arteriograms which the first study had revealed 7 months before. These three cases give an idea of the different radiological appearances of P.A.N. The appearance of endarteritis with no specific characteristics indicates and inflammatory localisation of the disease. This is an initial stage leading to ectasia. Aneurysms may progress to rupture or may multiply. Endarteritis and ectasia may also progress towards scarring and disappear. A method of early diagnosis, arteriography makes it possible to institute treatment before the lesions reach a stage at which they must inevitably develop either into aneurysms or lead to obstruction with distal ischaemia.", "contents": "[Arteriographic appearances seen in the course of development of the lesions of polyarteritis nodosa (author's transl)]. Three cases of polyarteritis nodosa (P.A.N.) studied by abdominal arteriography with a follow-up examination between the 6th and 9th month are reported. In the first case, the initial arteriogram showed only the appearances of endarteritis. The second arteriogram, 9 months later, following a worsening of general condition, revealed diffuse aneurysms in the abdomen. In the second patient, who had multiple aneurysms at the time of the initial examination, arteriography agter 6 months following a new episode of the disease with an acute abdominal syndrome and collapse revealed, alongside the multiplication of the aneurysms with rupture of one of them, the disappearance of some ectasias with the obliteration of certain arteries. In the third patient, the follow-up arteriogram after treatment showed disappearance of the renal arteriograms which the first study had revealed 7 months before. These three cases give an idea of the different radiological appearances of P.A.N. The appearance of endarteritis with no specific characteristics indicates and inflammatory localisation of the disease. This is an initial stage leading to ectasia. Aneurysms may progress to rupture or may multiply. Endarteritis and ectasia may also progress towards scarring and disappear. A method of early diagnosis, arteriography makes it possible to institute treatment before the lesions reach a stage at which they must inevitably develop either into aneurysms or lead to obstruction with distal ischaemia."}
{"id": "PMID:16131", "title": "The role of the urologist in barren marriages.", "content": "This paper is addressed to the gynecologist, who is generally the first to be consulted by the patient because of her failure to conceive. Early in the study there arises the problem of assigning individual factors. Is the patient involved solely, or is there also a male factor? Excluding the female's role to bear and nurture the fertilized cell until maturity, the frequency of subfertility in the male is just as great as it is in the female. Evaluation of the male should be done early in the study of the childless couple because it is less complex and less time consuming. Assignment of the relative fertility of husband and wife depends on the correlation of the findings in each. For that reason, also, treatment of the subfertile husband should not be undertaken until it is definitely determined that his wife is either reproductively normal or has remediable abnormalities. On the other hand, improvement of the fertility of one partner may be sufficient to induce pregnancy. Frequent communication between gynecologist and urologist is of utmost importance. An attempt is made to clarify for the gynecologist the abnormalities that may be encountered, the treatment to be employed and the prognosis. The mere fact that hormone administration is generally not effective in the male should not lead to the conclusion that treatment of the male is useless and that nothing can be done to improve his semen quality.", "contents": "The role of the urologist in barren marriages. This paper is addressed to the gynecologist, who is generally the first to be consulted by the patient because of her failure to conceive. Early in the study there arises the problem of assigning individual factors. Is the patient involved solely, or is there also a male factor? Excluding the female's role to bear and nurture the fertilized cell until maturity, the frequency of subfertility in the male is just as great as it is in the female. Evaluation of the male should be done early in the study of the childless couple because it is less complex and less time consuming. Assignment of the relative fertility of husband and wife depends on the correlation of the findings in each. For that reason, also, treatment of the subfertile husband should not be undertaken until it is definitely determined that his wife is either reproductively normal or has remediable abnormalities. On the other hand, improvement of the fertility of one partner may be sufficient to induce pregnancy. Frequent communication between gynecologist and urologist is of utmost importance. An attempt is made to clarify for the gynecologist the abnormalities that may be encountered, the treatment to be employed and the prognosis. The mere fact that hormone administration is generally not effective in the male should not lead to the conclusion that treatment of the male is useless and that nothing can be done to improve his semen quality."}
{"id": "PMID:16132", "title": "Synthesis and biological activity of some vinyl-substituted 2-nitroimidazoles.", "content": "In previous studies 1-methyl-2-nitro-1H-imidazole-5-carboxaldehyde and 1-methyl-2-nitro-5-vinyl-1H-imidazole were found to posses interesting antimicrobial activities. We have now prepared some 2-nitro-1H-imidazoles in which the 5-vinyl chain bears selected functional groups (CHO, COCH3, NO2) as well as nitrogen-condensation derivatives of the carbonyl functions. Furthermore, 5-methyl-2-nitro-1-vinyl-1H-imidazole has been synthesized. All the compounds, and some intermediates, have been assayed for antimicrobial activity. Several of them exhibited significant antibacterial and antitrichomonal activity in mice.", "contents": "Synthesis and biological activity of some vinyl-substituted 2-nitroimidazoles. In previous studies 1-methyl-2-nitro-1H-imidazole-5-carboxaldehyde and 1-methyl-2-nitro-5-vinyl-1H-imidazole were found to posses interesting antimicrobial activities. We have now prepared some 2-nitro-1H-imidazoles in which the 5-vinyl chain bears selected functional groups (CHO, COCH3, NO2) as well as nitrogen-condensation derivatives of the carbonyl functions. Furthermore, 5-methyl-2-nitro-1-vinyl-1H-imidazole has been synthesized. All the compounds, and some intermediates, have been assayed for antimicrobial activity. Several of them exhibited significant antibacterial and antitrichomonal activity in mice."}
{"id": "PMID:16133", "title": "N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor.", "content": "The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine.", "contents": "N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor. The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine."}
{"id": "PMID:16134", "title": "5-allyl-9-oxobenzomorphans. 3. Potent narcotic antagonists and analgesics-antagonists in the series of substituted 2',9beta-dihydroxy-6,7-benzomorphans.", "content": "5-Allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan methiodide (1) has been converted in a selective two-step process to the corresponding 9beta-hydroxy intermediates 4 and 6, which in turn were transformed via modified von Braun demethylation-acylation to the amides 11 and 21, respectively. These were reduced and demethylated to give a series of 5-allyl-2',9beta-dihydroxy-2-substituted 6,7-benzomorphans 13 and 23, some of which have been found to be highly potent narcotic antagonists and/or analgesics. The resolution of the most interesting compounds (23a and 23b) and pharmacological properties of the optical isomers are also described. Reduction of the double bond in 13 and 23 to give 14 and 24, with one exception, did not appreciably alter pharmacological profiles, while cyclization to the tetrahydrofuranobenzomorphans 25 substantially reduced the level of activities.", "contents": "5-allyl-9-oxobenzomorphans. 3. Potent narcotic antagonists and analgesics-antagonists in the series of substituted 2',9beta-dihydroxy-6,7-benzomorphans. 5-Allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan methiodide (1) has been converted in a selective two-step process to the corresponding 9beta-hydroxy intermediates 4 and 6, which in turn were transformed via modified von Braun demethylation-acylation to the amides 11 and 21, respectively. These were reduced and demethylated to give a series of 5-allyl-2',9beta-dihydroxy-2-substituted 6,7-benzomorphans 13 and 23, some of which have been found to be highly potent narcotic antagonists and/or analgesics. The resolution of the most interesting compounds (23a and 23b) and pharmacological properties of the optical isomers are also described. Reduction of the double bond in 13 and 23 to give 14 and 24, with one exception, did not appreciably alter pharmacological profiles, while cyclization to the tetrahydrofuranobenzomorphans 25 substantially reduced the level of activities."}
{"id": "PMID:16135", "title": "Synthesis and narcotic agonist-antagonist evaluation of some 2,6-methano-3-benzazocine-11 propanols. Analogues of the ring C bridged oripavine-7-mehtanols.", "content": "A general synthesis of variously substituted 2,6-methano-3-benzazocine-11-propanols is described. Nine N-CH3 derivatives and their corresponding N-cyclopropylmethyl counterparts were prepared and studied in the mouse acetylcholine induced writhing and rat phenazocine antagonism tests. The results are compared with literature information on the bridged oripavine methanols. It is concluded that the synthetic analogues have a different structure-activity profile, in general being weak agonists but potent antagonists.", "contents": "Synthesis and narcotic agonist-antagonist evaluation of some 2,6-methano-3-benzazocine-11 propanols. Analogues of the ring C bridged oripavine-7-mehtanols. A general synthesis of variously substituted 2,6-methano-3-benzazocine-11-propanols is described. Nine N-CH3 derivatives and their corresponding N-cyclopropylmethyl counterparts were prepared and studied in the mouse acetylcholine induced writhing and rat phenazocine antagonism tests. The results are compared with literature information on the bridged oripavine methanols. It is concluded that the synthetic analogues have a different structure-activity profile, in general being weak agonists but potent antagonists."}
{"id": "PMID:16136", "title": "Adrenergic agents. 4. Substituted phenoxypropanolamine derivatives as potential beta-adrenergic agonists.", "content": "A series of 1-(substituted phenoxy)-3-(tert-butylamino)-2-propanols in which the ring substituents were 3,4-dihydroxy (6f), 3- and 4-hydroxy (6g and 6h, respectively), 3-hydroxy-4-methylsulfonamido (6i), its 3,4-transposed isomer (6j), and 4-methylsulfonylmethyl (6k) was prepared and examined for beta-adrenergic agonist and/or antagonist properties. Two of these compounds, 6f and 6j, were potent beta-adrenoreceptor agonists in in vitro tests that measure a compound's ability to relax guinea pig tracheal smooth muscle and to increase the rate of contraction of guinea pig right atria. Several compounds had a dose-dependent effect. Although they produced potent beta-adrenergic agonist activity at low concentrations, 6g, 6h, and 6j antagonized the effects of a standard beta-adrenoreceptor agonist at higher concentrations. The methylsulfonylmethyl derivative 6k produced beta-adrenergic blocking effects as demonstrated by attenuation of isoproterenol-induced increases in the rate of contraction of an isolated rabbit heart preparation. On the basis of these pharmacological results, coupled with NMR spectral data, it appears that the previous suggestion that aryloxypropanolamines interact with beta-adrenocreceptors as a consequence of their ability to assume an orientation in which the benzene ring the ethanolamine moieties can be superimposed on those of corresponding adrenergic phenylethanolamines is invalid. An alternative \"bicyclic\" rigid conformation involving two intramolecular hydrogen bonds in the protonated form of the aryloxypropanolamines is suggested to account for the similar beta-adrenoreceptor activity of these compounds and related phenylethanolamines.", "contents": "Adrenergic agents. 4. Substituted phenoxypropanolamine derivatives as potential beta-adrenergic agonists. A series of 1-(substituted phenoxy)-3-(tert-butylamino)-2-propanols in which the ring substituents were 3,4-dihydroxy (6f), 3- and 4-hydroxy (6g and 6h, respectively), 3-hydroxy-4-methylsulfonamido (6i), its 3,4-transposed isomer (6j), and 4-methylsulfonylmethyl (6k) was prepared and examined for beta-adrenergic agonist and/or antagonist properties. Two of these compounds, 6f and 6j, were potent beta-adrenoreceptor agonists in in vitro tests that measure a compound's ability to relax guinea pig tracheal smooth muscle and to increase the rate of contraction of guinea pig right atria. Several compounds had a dose-dependent effect. Although they produced potent beta-adrenergic agonist activity at low concentrations, 6g, 6h, and 6j antagonized the effects of a standard beta-adrenoreceptor agonist at higher concentrations. The methylsulfonylmethyl derivative 6k produced beta-adrenergic blocking effects as demonstrated by attenuation of isoproterenol-induced increases in the rate of contraction of an isolated rabbit heart preparation. On the basis of these pharmacological results, coupled with NMR spectral data, it appears that the previous suggestion that aryloxypropanolamines interact with beta-adrenocreceptors as a consequence of their ability to assume an orientation in which the benzene ring the ethanolamine moieties can be superimposed on those of corresponding adrenergic phenylethanolamines is invalid. An alternative \"bicyclic\" rigid conformation involving two intramolecular hydrogen bonds in the protonated form of the aryloxypropanolamines is suggested to account for the similar beta-adrenoreceptor activity of these compounds and related phenylethanolamines."}
{"id": "PMID:16138", "title": "Plasmalemma transport of OH- in Chara corallina: dynamics of activation and deactivation.", "content": "The light-mediated, time-dependent rise in the pH value at the center of an alkaline band was analyzed using the methods of numerical analysis. From this analysis an expression of the time-dependent build-up of OH- efflux was obtained for these bands. This information can now be employed to determine whether the light-activated transport of OH- and HCO3- influences the electrical properties of the plasmalemma. The dark-induced deactivation of OH- transport was also characterized, revealing a transition from efflux to a transient influx phase during deactivation. Numerical analysis of the steady-state OH- diffusion pattern, established along the surface of an alkaline band, revealed that the OH- efflux width was wider than previously envisaged. It was also found the OH- sink regions exist on either side of the efflux zone. These, and other characteristics revealed by the numerical analysis, enabled us to extend the OH- transport model proposed by Lucas (J. Exp. Bot. 1975, 26:347).", "contents": "Plasmalemma transport of OH- in Chara corallina: dynamics of activation and deactivation. The light-mediated, time-dependent rise in the pH value at the center of an alkaline band was analyzed using the methods of numerical analysis. From this analysis an expression of the time-dependent build-up of OH- efflux was obtained for these bands. This information can now be employed to determine whether the light-activated transport of OH- and HCO3- influences the electrical properties of the plasmalemma. The dark-induced deactivation of OH- transport was also characterized, revealing a transition from efflux to a transient influx phase during deactivation. Numerical analysis of the steady-state OH- diffusion pattern, established along the surface of an alkaline band, revealed that the OH- efflux width was wider than previously envisaged. It was also found the OH- sink regions exist on either side of the efflux zone. These, and other characteristics revealed by the numerical analysis, enabled us to extend the OH- transport model proposed by Lucas (J. Exp. Bot. 1975, 26:347)."}
{"id": "PMID:16141", "title": "Growth of a heterologous tumor cell line in neonatal rats with graft-versus-host disease.", "content": "The ability of a hamster tumor cell line (T20) to grow and exhibit type H virus particles was significantly enhanced in neonatal DA rats with graft-versus-host disease (GVHD). Tumor growth peaked on days 4 and 7 in control littermates receiving adult syngeneic cells or no cells at birth, respectively, and then subsequently disappeared. However, tumor nodules in animals with GVHD became significantly larger than those in controls by day 7 and continued to grow until death. In addition, a marked plasma cell infiltration was noticed in such rapidly growing tumors from animals with GVHD only. In the light of previous studies, evidence is discussed for an environment within animals with GVHD conducive for tumor cell growth because of a depletion of T-cell areas within their tissues.", "contents": "Growth of a heterologous tumor cell line in neonatal rats with graft-versus-host disease. The ability of a hamster tumor cell line (T20) to grow and exhibit type H virus particles was significantly enhanced in neonatal DA rats with graft-versus-host disease (GVHD). Tumor growth peaked on days 4 and 7 in control littermates receiving adult syngeneic cells or no cells at birth, respectively, and then subsequently disappeared. However, tumor nodules in animals with GVHD became significantly larger than those in controls by day 7 and continued to grow until death. In addition, a marked plasma cell infiltration was noticed in such rapidly growing tumors from animals with GVHD only. In the light of previous studies, evidence is discussed for an environment within animals with GVHD conducive for tumor cell growth because of a depletion of T-cell areas within their tissues."}
{"id": "PMID:16142", "title": "Carcinoma in situ of the ectopic testis.", "content": "A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis.", "contents": "Carcinoma in situ of the ectopic testis. A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis."}
{"id": "PMID:16143", "title": "Childhood gonadoblastoma and seminoma in a dysgenetic cryptorchid gonad.", "content": "A case of gonadoblastoma and seminoma occurring in a genotypic male child with ambiguous genitalia is presented. A review of the literature establishes that children with intersex disorders who possess a Y chromosome and undescended gonads stand a particularly high risk of having this type of gonadal neoplasm and should be explored.", "contents": "Childhood gonadoblastoma and seminoma in a dysgenetic cryptorchid gonad. A case of gonadoblastoma and seminoma occurring in a genotypic male child with ambiguous genitalia is presented. A review of the literature establishes that children with intersex disorders who possess a Y chromosome and undescended gonads stand a particularly high risk of having this type of gonadal neoplasm and should be explored."}
{"id": "PMID:16144", "title": "Acute bacteremia in asplenic renal transplant patients.", "content": "Four cases of overwhelming bacteremia were observed in asplenic renal transplant patients 12 to 20 months after transplantation. The bacteriologic findings and presentation of these infections are characteristic of post-splenectomy sepsis reported in nontransplant patients. It is suggested that the absence of the spleen, more than immunosuppression with azathioprine and prednisone, predisposes to these late, uncommon infections after transplantation.", "contents": "Acute bacteremia in asplenic renal transplant patients. Four cases of overwhelming bacteremia were observed in asplenic renal transplant patients 12 to 20 months after transplantation. The bacteriologic findings and presentation of these infections are characteristic of post-splenectomy sepsis reported in nontransplant patients. It is suggested that the absence of the spleen, more than immunosuppression with azathioprine and prednisone, predisposes to these late, uncommon infections after transplantation."}
{"id": "PMID:16145", "title": "Prune-belly syndrome in a 54-year-old man.", "content": "A 54-year-old man was diagnosed as having prune-belly syndrome, a deficiency of abdominal musculature, cryptorchidism, abnormalities of the urinary tract, and chronic renal failure. The patient was asymptomatic until the diagnosis was made at the age of 54 years; he is one of the oldest living patients to be reported in detail. Recognition of the syndrome in adults with chronic renal failure is important.", "contents": "Prune-belly syndrome in a 54-year-old man. A 54-year-old man was diagnosed as having prune-belly syndrome, a deficiency of abdominal musculature, cryptorchidism, abnormalities of the urinary tract, and chronic renal failure. The patient was asymptomatic until the diagnosis was made at the age of 54 years; he is one of the oldest living patients to be reported in detail. Recognition of the syndrome in adults with chronic renal failure is important."}
{"id": "PMID:16149", "title": "Antibiotic susceptibility of Streptococcus pneumoniae isolated from clinical materials (author's transl).", "content": "We tested the drug-susceptibility of 112 strains of Streptococcus pneumoniae isolated from various clinical materials since January 1975 to May 1976, and observed the changes of susceptibility of this pathogen. All strains tested remained very sensitive to benzylpenicillin and cephaloridine, but 59.8% of strains were resistant to tetracycline and 44.7% to chloramphenicol, and about 90% of chloramphenicol-resistant strains were also resistant to tetracycline. The percentage of resistant strains to tetracycline or chloramphenicol is increasing. Cross-resistance between tetracycline and doxycycline or chloramphenicol and thiamphenicol was observed. On this time we found three strains resistant to macrolides. Two of these strains were resistant to erythromycin, josamycin, oleandomycin, spiarmycin, mydecamycin, lincomycin, clindamycin and tetracycline, but one was resistant to josamycin, spiramycin, mydecamycin and chloramphenicol.", "contents": "Antibiotic susceptibility of Streptococcus pneumoniae isolated from clinical materials (author's transl). We tested the drug-susceptibility of 112 strains of Streptococcus pneumoniae isolated from various clinical materials since January 1975 to May 1976, and observed the changes of susceptibility of this pathogen. All strains tested remained very sensitive to benzylpenicillin and cephaloridine, but 59.8% of strains were resistant to tetracycline and 44.7% to chloramphenicol, and about 90% of chloramphenicol-resistant strains were also resistant to tetracycline. The percentage of resistant strains to tetracycline or chloramphenicol is increasing. Cross-resistance between tetracycline and doxycycline or chloramphenicol and thiamphenicol was observed. On this time we found three strains resistant to macrolides. Two of these strains were resistant to erythromycin, josamycin, oleandomycin, spiarmycin, mydecamycin, lincomycin, clindamycin and tetracycline, but one was resistant to josamycin, spiramycin, mydecamycin and chloramphenicol."}
{"id": "PMID:16151", "title": "T cell function detected in murine bone marrow cells.", "content": "Mouse bone marrow cells were fractionated by BSA discontinuous density gradient centrifugation, and a small lymphocyte rich fraction was obtained at the high density. Cells of this fraction were shown to respond in vitro to T cell mitogens and alloantigens. Furthermore, they were able to mount a graft-versus-host reaction when assessed by spleen weight assay and by the method of inhibiting erythroid cell growth by allogeneic lymphoid cells. The results indicate that these lymphocytes possess T cell functions. On the other hand they were found to carry only little theta antigen assessed by the cytotoxic test and by the absorption test. It is presumed, therefore, that the amount of theta antigen on a cell might not correlate with T cell functions, and these lymphocytes might be mature ones in the course of postthymic maturation. Hemopoietic stem cells were determined by spleen colony formation and the peak of colony-forming efficiency was seen at the low density. These observations imply that immunocompetent cells causing GVHR can be separated from hemopoietic stem cells. This procedure may be applied for prevention and reduction of GVHR in allogeneic bone marrow transplantation in human.", "contents": "T cell function detected in murine bone marrow cells. Mouse bone marrow cells were fractionated by BSA discontinuous density gradient centrifugation, and a small lymphocyte rich fraction was obtained at the high density. Cells of this fraction were shown to respond in vitro to T cell mitogens and alloantigens. Furthermore, they were able to mount a graft-versus-host reaction when assessed by spleen weight assay and by the method of inhibiting erythroid cell growth by allogeneic lymphoid cells. The results indicate that these lymphocytes possess T cell functions. On the other hand they were found to carry only little theta antigen assessed by the cytotoxic test and by the absorption test. It is presumed, therefore, that the amount of theta antigen on a cell might not correlate with T cell functions, and these lymphocytes might be mature ones in the course of postthymic maturation. Hemopoietic stem cells were determined by spleen colony formation and the peak of colony-forming efficiency was seen at the low density. These observations imply that immunocompetent cells causing GVHR can be separated from hemopoietic stem cells. This procedure may be applied for prevention and reduction of GVHR in allogeneic bone marrow transplantation in human."}
{"id": "PMID:16152", "title": "Physicochemical properties of a liquid ion exchanger microelectrode and its application to biological fluids.", "content": "Double-barreled potassium or chloride ion-selective microelectrodes were constructed using a liquid ion exchanger. Technical details of the fabrication of double-barreled microelectrodes, having a PD sensor as one barrel and an ionic sensor as the other, are described. The sensitivity of K+ or CI- ion-selective microelectrodes exhibited an approximately Nernstian response over a temperature range of 7 degrees-37 degrees C, and the electromotive force (EMF) was stable within +/- mV for a few hours. The rise time was less than 1 sec. The effect of pH on the electrode response was negligible over a physiological range of pH 5.6 to 7.8. The selectivity constants of the K+ microelectrode to other cations were 0.011 for Na+, 0.200 for NH+4, and less than 0.002 and 0.001 for Ca++ and Mg++, respectively, while that of the CI- microelectrode was 0.067 for HCO-3. Glucose or urea has no effect on the EMF. Protein has a significant effect on ion exchanger membrane only when the concentration of the tested ion is low and protein is high. On the basis of this background the determination of K+ and CI- activity was carried out both in vivo and in vitro on several biological samples, such as serum, tissue and cellular fluids, and other protein-containing fluids. The values obtained with the microelectrode were consistent with those obtained with the other conventional methods or with the current theory on electrolyte solutions. These results were taken to assure the practical application of these electrodes to biological studies in many fields.", "contents": "Physicochemical properties of a liquid ion exchanger microelectrode and its application to biological fluids. Double-barreled potassium or chloride ion-selective microelectrodes were constructed using a liquid ion exchanger. Technical details of the fabrication of double-barreled microelectrodes, having a PD sensor as one barrel and an ionic sensor as the other, are described. The sensitivity of K+ or CI- ion-selective microelectrodes exhibited an approximately Nernstian response over a temperature range of 7 degrees-37 degrees C, and the electromotive force (EMF) was stable within +/- mV for a few hours. The rise time was less than 1 sec. The effect of pH on the electrode response was negligible over a physiological range of pH 5.6 to 7.8. The selectivity constants of the K+ microelectrode to other cations were 0.011 for Na+, 0.200 for NH+4, and less than 0.002 and 0.001 for Ca++ and Mg++, respectively, while that of the CI- microelectrode was 0.067 for HCO-3. Glucose or urea has no effect on the EMF. Protein has a significant effect on ion exchanger membrane only when the concentration of the tested ion is low and protein is high. On the basis of this background the determination of K+ and CI- activity was carried out both in vivo and in vitro on several biological samples, such as serum, tissue and cellular fluids, and other protein-containing fluids. The values obtained with the microelectrode were consistent with those obtained with the other conventional methods or with the current theory on electrolyte solutions. These results were taken to assure the practical application of these electrodes to biological studies in many fields."}
{"id": "PMID:16153", "title": "Effects of intracellular pH on plateau formation following the action potential of squid giant axons.", "content": "When squid giant axons were intracellularly perfused for about 10 min with 100 mM K+ solutions containing Pronase or Protease Type VII at a concentration of 0.1-0.5 mg/ml, the action potential developed a long-lasting plateau. The plateau persisted after switching to an enzyme-free solution at standard pH (7.3 +/- 0.1) as the intracellular perfusate. The plateau was promptly and completely suppressed when the intracellular pH was lowered below 6.5. Upon increase of pH again to the standard level, the plateau promptly reappeared. With alkaline intracellular pH plateau formation was enhanced. Lowering the pH of the extracellular medium to 5 did not influence the plateau. The duration of the action potential under bi-ionic conditions (inside Cs+, outside Ca++) decreased with low intracellular pH and increased with high intracellular pH. The plateau duration of the action potential from axons intracellularly perfused with solutions containing 10 mM tetraethylammonium also decreased with low intracellular pH and increased with high intracellular pH. The underlying mechanisms for the pH effects remain to be explored.", "contents": "Effects of intracellular pH on plateau formation following the action potential of squid giant axons. When squid giant axons were intracellularly perfused for about 10 min with 100 mM K+ solutions containing Pronase or Protease Type VII at a concentration of 0.1-0.5 mg/ml, the action potential developed a long-lasting plateau. The plateau persisted after switching to an enzyme-free solution at standard pH (7.3 +/- 0.1) as the intracellular perfusate. The plateau was promptly and completely suppressed when the intracellular pH was lowered below 6.5. Upon increase of pH again to the standard level, the plateau promptly reappeared. With alkaline intracellular pH plateau formation was enhanced. Lowering the pH of the extracellular medium to 5 did not influence the plateau. The duration of the action potential under bi-ionic conditions (inside Cs+, outside Ca++) decreased with low intracellular pH and increased with high intracellular pH. The plateau duration of the action potential from axons intracellularly perfused with solutions containing 10 mM tetraethylammonium also decreased with low intracellular pH and increased with high intracellular pH. The underlying mechanisms for the pH effects remain to be explored."}
{"id": "PMID:16154", "title": "Effects of sodium bicarbonate administration during cardiopulmonary resuscitation.", "content": "To study whether sodium bicarbonate given in cardiopulmonary resuscitation may produce life-threatening hyperosmolality or hypernatremia, arterial blood was analysed for blood gas, alcohol, blood urea nitrogen, electrolyte and osmolality. The blood was drawn after resuscitation in successful cases, and while effective massage and ventilation were being applied in unsuccessful resuscitations. Seven of the 17 resuscitations were successful. Serum sodium concentrations ranged from 135 to 154 with one exception and did not correlate with the amount of sodium bicarbonate administered. Arterial pH ranged from 6.38 to 7.71; only one patient had metabolic alkalosis. Serum osmolality ranged from 301 to 407. The data suggests a net increase in osmolality of 6 mOsm/50 mEq of sodium bicarbonate.", "contents": "Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. To study whether sodium bicarbonate given in cardiopulmonary resuscitation may produce life-threatening hyperosmolality or hypernatremia, arterial blood was analysed for blood gas, alcohol, blood urea nitrogen, electrolyte and osmolality. The blood was drawn after resuscitation in successful cases, and while effective massage and ventilation were being applied in unsuccessful resuscitations. Seven of the 17 resuscitations were successful. Serum sodium concentrations ranged from 135 to 154 with one exception and did not correlate with the amount of sodium bicarbonate administered. Arterial pH ranged from 6.38 to 7.71; only one patient had metabolic alkalosis. Serum osmolality ranged from 301 to 407. The data suggests a net increase in osmolality of 6 mOsm/50 mEq of sodium bicarbonate."}
{"id": "PMID:16155", "title": "Cryptorchidism and abdominal pain.", "content": "In this case report, abdominal symptoms simulating acute appendicitis were due to recurrent torsion of an intra-abdominal testicle. Cryptorchidism frequently goes unnoted. Most undescended testicles are in the groin and easily palpable. If not, they can be absent, retroperitoneal or intra-abdominal. An intra-abdominal testicle is more likely to occur on the right than the left.", "contents": "Cryptorchidism and abdominal pain. In this case report, abdominal symptoms simulating acute appendicitis were due to recurrent torsion of an intra-abdominal testicle. Cryptorchidism frequently goes unnoted. Most undescended testicles are in the groin and easily palpable. If not, they can be absent, retroperitoneal or intra-abdominal. An intra-abdominal testicle is more likely to occur on the right than the left."}
{"id": "PMID:16156", "title": "Acid-base relationships in the different body compartments: the basis for a simplified diagnostic approach.", "content": "Special characteristics of cellular buffering must be taken into account in order to describe accurately acid-base relationships in the whole body. In particular, tissues other than blood are able to neutralize mineral acid independent of changes in Pco(2) and hence independent of large changes in extra- and intracellular pH. Although mechanistic details remain to be clarified, relationships that describe this tissue buffering in quantitative terms are well established. In this report, emphasis is placed on quantitative relationships that stress the need for diagnostic interpretation derived from acid-base changes within the whole body rather than simply within the blood compartment. Theoreticalproblems with respect ot buffering mechanisms in various body compartments are reviewed and analyzed.", "contents": "Acid-base relationships in the different body compartments: the basis for a simplified diagnostic approach. Special characteristics of cellular buffering must be taken into account in order to describe accurately acid-base relationships in the whole body. In particular, tissues other than blood are able to neutralize mineral acid independent of changes in Pco(2) and hence independent of large changes in extra- and intracellular pH. Although mechanistic details remain to be clarified, relationships that describe this tissue buffering in quantitative terms are well established. In this report, emphasis is placed on quantitative relationships that stress the need for diagnostic interpretation derived from acid-base changes within the whole body rather than simply within the blood compartment. Theoreticalproblems with respect ot buffering mechanisms in various body compartments are reviewed and analyzed."}
{"id": "PMID:16157", "title": "[Use of coronaroactive agents with beta-stimulating effect in ischemic heart disease].", "content": "In feline experiments and 65 clinical cases of ischaemic heart disease the efficacy of a new beta-stimulating agetn -- Ildamen -- was studied, the obtained effect was compared to that of Euphillin. Ildamen was found to be highly effective in patients with a moderately decreased coronary reserve and without atherosclerotic lesions in the coronary vessels.", "contents": "[Use of coronaroactive agents with beta-stimulating effect in ischemic heart disease]. In feline experiments and 65 clinical cases of ischaemic heart disease the efficacy of a new beta-stimulating agetn -- Ildamen -- was studied, the obtained effect was compared to that of Euphillin. Ildamen was found to be highly effective in patients with a moderately decreased coronary reserve and without atherosclerotic lesions in the coronary vessels."}
{"id": "PMID:16160", "title": "Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities.", "content": "The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence of imposed bicarbonate ion gradients, comparable to those occurring in vivo. With mucosal (M) pH lowered to the point of zero net hydrogen ion secretion, the transepithelial flow of bicarbonate ions (JHCO3) from serosa (S) to M was 0.91 +/- .06 y mole/hr in response to a 20 mM HCO3- gradient. After AMB addition to M, back diffusion of hydrogen ions from M to S (-JH) increased from zero to 0.36+/-0.05 micronmole/hr, whereas bicarbonate ion transport from S to M (JHCO3) failed to increase (0.91+/-0.06 before and 0.82+/-0.09 micronmole/hr after AMB). In contrast to M addition, S addition of AMB had no effect on either -JH or JHCO3. The defect in urinary acidification induced by AMB is characterized by a large increase in the permeability for hydrogen ions rather than that for bicarbonate ions and depends on direct exposure of the luminal cell membrane to AMB. The permeability increase is cation selective, not only for hydrogen ions but also, as shown previously, for potassium ions, and to a lesser extent, for sodium ions. The results are consistent with the formation by AMB of aqueous half pores in the luminal membrane. Although the passive permeabilities for bicarbonate and chloride ions are not affected primarily, they may increase after prolonged exposure, probably as a results of paracellular leaks that are not specific for AMB.", "contents": "Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities. The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence of imposed bicarbonate ion gradients, comparable to those occurring in vivo. With mucosal (M) pH lowered to the point of zero net hydrogen ion secretion, the transepithelial flow of bicarbonate ions (JHCO3) from serosa (S) to M was 0.91 +/- .06 y mole/hr in response to a 20 mM HCO3- gradient. After AMB addition to M, back diffusion of hydrogen ions from M to S (-JH) increased from zero to 0.36+/-0.05 micronmole/hr, whereas bicarbonate ion transport from S to M (JHCO3) failed to increase (0.91+/-0.06 before and 0.82+/-0.09 micronmole/hr after AMB). In contrast to M addition, S addition of AMB had no effect on either -JH or JHCO3. The defect in urinary acidification induced by AMB is characterized by a large increase in the permeability for hydrogen ions rather than that for bicarbonate ions and depends on direct exposure of the luminal cell membrane to AMB. The permeability increase is cation selective, not only for hydrogen ions but also, as shown previously, for potassium ions, and to a lesser extent, for sodium ions. The results are consistent with the formation by AMB of aqueous half pores in the luminal membrane. Although the passive permeabilities for bicarbonate and chloride ions are not affected primarily, they may increase after prolonged exposure, probably as a results of paracellular leaks that are not specific for AMB."}
{"id": "PMID:16171", "title": "[The role of proximal osteomy of the tibia in the treatment of arthrosis of the knee joint].", "content": "The results of heigh tibia osteotomy performed between 1970 and 1975 in 20 cases in the material of the Orthopaedic Department of the \"Semmelweis\" University Medical School, Budapest, are reported. In 13 cases good--in 6 cases satisfactory results have been obtained. In 1 case the surgical intervention was of no effect. With regard to the explicit pain-relieving effect the operation is recommended by the authors in the treatment of knee arthrosis.", "contents": "[The role of proximal osteomy of the tibia in the treatment of arthrosis of the knee joint]. The results of heigh tibia osteotomy performed between 1970 and 1975 in 20 cases in the material of the Orthopaedic Department of the \"Semmelweis\" University Medical School, Budapest, are reported. In 13 cases good--in 6 cases satisfactory results have been obtained. In 1 case the surgical intervention was of no effect. With regard to the explicit pain-relieving effect the operation is recommended by the authors in the treatment of knee arthrosis."}
{"id": "PMID:16172", "title": "[Restoration problems in frontoglabellar skull defects].", "content": "Replacement problems of frontoglabellar skull defects and their recent operative methods come under review. A new method for the prevention of infection of paranasal sinus origin is reported in the article. Possibilities for producing good contour frontal area prothesis are considered here. The new method developed by the authors for orbital roof replacement is justified not only by cosmetics but physiology as well.", "contents": "[Restoration problems in frontoglabellar skull defects]. Replacement problems of frontoglabellar skull defects and their recent operative methods come under review. A new method for the prevention of infection of paranasal sinus origin is reported in the article. Possibilities for producing good contour frontal area prothesis are considered here. The new method developed by the authors for orbital roof replacement is justified not only by cosmetics but physiology as well."}
{"id": "PMID:16173", "title": "[Post-traumatic protrusion of the hip joint].", "content": "23 patients with post-traumatic protrusion of the hip joint--due to fracture of the base of the acetabulum--have been re-examined by the authors. On the basis of the radiomorphological alterations developed in consequence of the fracture and according to the severity of the articular deformation the cases have been classified into four categories. The relationship between the morphological alteration, the functional ability of the joint and the subsequent arthrosis--as well as the problems of the social rehabilitation are discussed.", "contents": "[Post-traumatic protrusion of the hip joint]. 23 patients with post-traumatic protrusion of the hip joint--due to fracture of the base of the acetabulum--have been re-examined by the authors. On the basis of the radiomorphological alterations developed in consequence of the fracture and according to the severity of the articular deformation the cases have been classified into four categories. The relationship between the morphological alteration, the functional ability of the joint and the subsequent arthrosis--as well as the problems of the social rehabilitation are discussed."}
{"id": "PMID:16174", "title": "[Malignant degeneration of chronic suppurative bone diseases].", "content": "Out of 1189 patients with osteomyelitis of the Hungarian Institute of Medical Rehabilitation malignant degeneration in the region of purulent bone process has been observed in 6 cases by the authors. Out of them 5 cases were carcinoma planocellulare and 1 case was sarcoma gigantocellulare. During the detailed analyses of the cases it is pointed out by the authors that on the basis of the standpoint established regarding the rehabilitation in locomotor diseases the indication of the amputation in patients with osteomyelitis is not absolutely limited to the cases undoubtedly malignized. Rehabilitation and resocialization of the patients is better promoted with the performed amputation and the up-to-date manufactured prosthesis than by a series of unsuccessful and hazardous therapeutical experiments.", "contents": "[Malignant degeneration of chronic suppurative bone diseases]. Out of 1189 patients with osteomyelitis of the Hungarian Institute of Medical Rehabilitation malignant degeneration in the region of purulent bone process has been observed in 6 cases by the authors. Out of them 5 cases were carcinoma planocellulare and 1 case was sarcoma gigantocellulare. During the detailed analyses of the cases it is pointed out by the authors that on the basis of the standpoint established regarding the rehabilitation in locomotor diseases the indication of the amputation in patients with osteomyelitis is not absolutely limited to the cases undoubtedly malignized. Rehabilitation and resocialization of the patients is better promoted with the performed amputation and the up-to-date manufactured prosthesis than by a series of unsuccessful and hazardous therapeutical experiments."}
{"id": "PMID:16175", "title": "[Ultrastructural changes in the skeletal muscles following nerve and tendon injuries in man. II. Nerve injuries].", "content": "The alterations occuring in the fine structure of the man's hand muscles after traumatic nerve injuries have been examined by the authors. In the muscle portions taken in the 6th--16th weeks after the injury considerable atrophy of the contractile components, the desorganisation of the myofilaments, and the atropy of the mitochondrium and the sarcoplasmatic reticulum have been observed. The motor end-organs are athropic or their place is indicated but by a single great vacuolum. In the motor nerve fibres the typical picture of Waller's degeneration was seen.", "contents": "[Ultrastructural changes in the skeletal muscles following nerve and tendon injuries in man. II. Nerve injuries]. The alterations occuring in the fine structure of the man's hand muscles after traumatic nerve injuries have been examined by the authors. In the muscle portions taken in the 6th--16th weeks after the injury considerable atrophy of the contractile components, the desorganisation of the myofilaments, and the atropy of the mitochondrium and the sarcoplasmatic reticulum have been observed. The motor end-organs are athropic or their place is indicated but by a single great vacuolum. In the motor nerve fibres the typical picture of Waller's degeneration was seen."}
{"id": "PMID:16176", "title": "[Structure and configuration of human tendons. II. Development of tendon structure during ontogenesis].", "content": "In infants born in the 24th--30th weeks of the gravidity the praenatal development and the process of the organization of the tendinous structure have been examined by the authors. By means of photo- and polarization microscopic examinations it was found that the tendon of the flexor hand muscles (M. flexor carpi radialis, M. flexor digitorum comm.) shows mature tendinous structure earlier, than the tendons of the flexor muscles of the lower extremity (M. semitendinosus femoris, M. triceps surae). The tendons of the extensor muscles of the lower extremity (M. quadriceps femoris, M. tibialis ant.) are underdeveloped and inordinate in the foetal life--their structure develops only during the postnatal life.", "contents": "[Structure and configuration of human tendons. II. Development of tendon structure during ontogenesis]. In infants born in the 24th--30th weeks of the gravidity the praenatal development and the process of the organization of the tendinous structure have been examined by the authors. By means of photo- and polarization microscopic examinations it was found that the tendon of the flexor hand muscles (M. flexor carpi radialis, M. flexor digitorum comm.) shows mature tendinous structure earlier, than the tendons of the flexor muscles of the lower extremity (M. semitendinosus femoris, M. triceps surae). The tendons of the extensor muscles of the lower extremity (M. quadriceps femoris, M. tibialis ant.) are underdeveloped and inordinate in the foetal life--their structure develops only during the postnatal life."}
{"id": "PMID:16177", "title": "[Synovial chondrochromatosis of the metacarpophalangeal joint].", "content": "A rare case of synovial chondromatosis sited on the IVth metacarpophalangeal articulation of the left hand of a women is reported. The pathogenesis, the histology and the method of treatment are discussed. 2 years after the operation the patient is symptom-free and without complaints.", "contents": "[Synovial chondrochromatosis of the metacarpophalangeal joint]. A rare case of synovial chondromatosis sited on the IVth metacarpophalangeal articulation of the left hand of a women is reported. The pathogenesis, the histology and the method of treatment are discussed. 2 years after the operation the patient is symptom-free and without complaints."}
{"id": "PMID:16178", "title": "[Oto-palato-digital (Taybi) syndrome].", "content": "A case of dysmorphogenetic syndrome, described by Taybi, is reported. The syndrome is characterized by hardness of hearing of conduction type, submucous cleft palate and anomalies involving the bony frame, especially the digits.", "contents": "[Oto-palato-digital (Taybi) syndrome]. A case of dysmorphogenetic syndrome, described by Taybi, is reported. The syndrome is characterized by hardness of hearing of conduction type, submucous cleft palate and anomalies involving the bony frame, especially the digits."}
{"id": "PMID:16179", "title": "[Luxation fracture of the hip joint. I. Posterior fractures with dislocation].", "content": "41 cases of posterior sprain fracture are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. On the basis of the late results it is stated by the authors that the immediate diagnosis and the reposition of the luxation are of the greatest importance. Conservative treatment yields generally satisfactory results. In the authors' opinion, osteosynthesis is indicated but in fractures concomitant with the fracture and dislocation of great piece of the acetabulum and in juvenile patients.", "contents": "[Luxation fracture of the hip joint. I. Posterior fractures with dislocation]. 41 cases of posterior sprain fracture are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. On the basis of the late results it is stated by the authors that the immediate diagnosis and the reposition of the luxation are of the greatest importance. Conservative treatment yields generally satisfactory results. In the authors' opinion, osteosynthesis is indicated but in fractures concomitant with the fracture and dislocation of great piece of the acetabulum and in juvenile patients."}
{"id": "PMID:16180", "title": "[Local soft tissue ossification of traumatic origin].", "content": "Under the effect of trauma, in 4 patients the development of metaplastic bone-tissue in the soft-parts of mesenchymal origin has been observed by the author. In 3 patients the development of supernumerary articulations proved the appearance of cartilaginous tissue; in consequence, the presence of cartilaginous tissue may play an important role in the metaplastic soft-parts ossification.", "contents": "[Local soft tissue ossification of traumatic origin]. Under the effect of trauma, in 4 patients the development of metaplastic bone-tissue in the soft-parts of mesenchymal origin has been observed by the author. In 3 patients the development of supernumerary articulations proved the appearance of cartilaginous tissue; in consequence, the presence of cartilaginous tissue may play an important role in the metaplastic soft-parts ossification."}
{"id": "PMID:16184", "title": "A systems analysis of the impact of physician extenders on medical cost and manpower requirements.", "content": "This paper presents a descriptive narrative of a mathematical manpower model and the results of an analysis of the effect physician extenders have on medical costs and manpower requirements. The model is extensively developed, through the use of a new medical classification system in the area of delegation of specific task areas and patient visits to physician extenders. Additionally the models incorporate a complete cost structure for a group practice. Field trials in seven HMOs indicate that the models accurately represent the actual system and can be used effectively as planning aids. Results are presented that analyze the use of physician extenders from the following viewpoints: minimum cost solution for adult medicine, pediatrics and obstetrics/gynecology (OB/GYN); maximum physician extender use; effect of physician extender salary on minimum cost utilization; level of independence exercised; size of clinic and regional manpower planning; and a case study of HMO planning. The type of results presented include cost analysis, manpower analysis, and the types of patient visits best delegated to physician extenders (PE).", "contents": "A systems analysis of the impact of physician extenders on medical cost and manpower requirements. This paper presents a descriptive narrative of a mathematical manpower model and the results of an analysis of the effect physician extenders have on medical costs and manpower requirements. The model is extensively developed, through the use of a new medical classification system in the area of delegation of specific task areas and patient visits to physician extenders. Additionally the models incorporate a complete cost structure for a group practice. Field trials in seven HMOs indicate that the models accurately represent the actual system and can be used effectively as planning aids. Results are presented that analyze the use of physician extenders from the following viewpoints: minimum cost solution for adult medicine, pediatrics and obstetrics/gynecology (OB/GYN); maximum physician extender use; effect of physician extender salary on minimum cost utilization; level of independence exercised; size of clinic and regional manpower planning; and a case study of HMO planning. The type of results presented include cost analysis, manpower analysis, and the types of patient visits best delegated to physician extenders (PE)."}
{"id": "PMID:16185", "title": "Physician receptivity to nurse practitioners: a study of the correlates of the delegation of clinical responsibility.", "content": "A survey to measure physician receptivity to nurse practitioners was conducted in North Carolina in 1973. All North Carolina physicians were asked to rate a list of 35 clinical tasks of varying levels of difficulty and responsibility according to their willingness to delegate these tasks to nurse practitioners. Using eight items from this list that were good discriminants of physician attitudes towards delegating responsibility, task delegation scores were correlated with physician characteristics and their responses to questions about recruitment, training, reimbursement, and willingness to hire nurse practitioners. Thirty-four per cent of the respondents would hire a nurse practitioner, whereas 52% approved of the concept but would not hire one. Physicians who had previously worked with a nurse practitioner were more willing to hire one and had a higher task delegation score. Sixty-eight per cent of respondents would share their load with nurse practitioners in their offices, while 6% would have them work in satellite clinics away from the physicians' offices. Most physicians wanted their own nurse trained as a nurse practitioner in a program that combined a didactic course at a medical center with on-the-job training. The authors conclude that there is a potential demand for nurse practitioners in North Carolina and that the training program must prepare the nurse practitioners for the tasks physicians are willing to delegate to them.", "contents": "Physician receptivity to nurse practitioners: a study of the correlates of the delegation of clinical responsibility. A survey to measure physician receptivity to nurse practitioners was conducted in North Carolina in 1973. All North Carolina physicians were asked to rate a list of 35 clinical tasks of varying levels of difficulty and responsibility according to their willingness to delegate these tasks to nurse practitioners. Using eight items from this list that were good discriminants of physician attitudes towards delegating responsibility, task delegation scores were correlated with physician characteristics and their responses to questions about recruitment, training, reimbursement, and willingness to hire nurse practitioners. Thirty-four per cent of the respondents would hire a nurse practitioner, whereas 52% approved of the concept but would not hire one. Physicians who had previously worked with a nurse practitioner were more willing to hire one and had a higher task delegation score. Sixty-eight per cent of respondents would share their load with nurse practitioners in their offices, while 6% would have them work in satellite clinics away from the physicians' offices. Most physicians wanted their own nurse trained as a nurse practitioner in a program that combined a didactic course at a medical center with on-the-job training. The authors conclude that there is a potential demand for nurse practitioners in North Carolina and that the training program must prepare the nurse practitioners for the tasks physicians are willing to delegate to them."}
{"id": "PMID:16191", "title": "Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo.", "content": "(--)-Hydroxycitrate and (+)-allo-hydroxycitrate were investigated for their effects on lipid synthesis in vivo under conditions of either high carbohydrate feeding or 24 hr fasting. Changes in rates of lipid synthesis resulting from the oral administration of these compounds were monitored with the use of radiolabeled H2O, alanine, and acetate. In the fed rat, (--)-hydroxycitrate significantly reduced the incorporation of H2O and alanine into fatty acids and cholesterol. An increased incorporation of labeled H2O into fatty acids but no change in cholesterol synthesis in the fasted rat suggested that (--)-hydroxycitrate may be an activator of acetyl CoA carboxylase. With (--)-hydroxycitrate administration, acetate incorporation into fatty acids and cholesterol was subject to pool dilution effects under fed or fasted states. (+)-allo-Hydroxycitrate was ineffective in modulating the rates of fatty acid synthesis under either nutritional condition. Both (--)-hydroxycitrate and (+)-allo-hydroxycitrate were shown to be in vitro activators of acetyl CoA carboxylase, the former being a much stronger activator than the latter. Thus, stereospecificity of the hydroxycitrate isomers was demonstrated in both the inhibition of lipid synthesis (previously shown to occur at adenosine triphosphate citrate lyase) and the stimulation of fatty acid synthesis (possibly occurring at acetyl CoA carboxylase).", "contents": "Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. (--)-Hydroxycitrate and (+)-allo-hydroxycitrate were investigated for their effects on lipid synthesis in vivo under conditions of either high carbohydrate feeding or 24 hr fasting. Changes in rates of lipid synthesis resulting from the oral administration of these compounds were monitored with the use of radiolabeled H2O, alanine, and acetate. In the fed rat, (--)-hydroxycitrate significantly reduced the incorporation of H2O and alanine into fatty acids and cholesterol. An increased incorporation of labeled H2O into fatty acids but no change in cholesterol synthesis in the fasted rat suggested that (--)-hydroxycitrate may be an activator of acetyl CoA carboxylase. With (--)-hydroxycitrate administration, acetate incorporation into fatty acids and cholesterol was subject to pool dilution effects under fed or fasted states. (+)-allo-Hydroxycitrate was ineffective in modulating the rates of fatty acid synthesis under either nutritional condition. Both (--)-hydroxycitrate and (+)-allo-hydroxycitrate were shown to be in vitro activators of acetyl CoA carboxylase, the former being a much stronger activator than the latter. Thus, stereospecificity of the hydroxycitrate isomers was demonstrated in both the inhibition of lipid synthesis (previously shown to occur at adenosine triphosphate citrate lyase) and the stimulation of fatty acid synthesis (possibly occurring at acetyl CoA carboxylase)."}
{"id": "PMID:16194", "title": "Fetal fuels. I. Utilization of ketones by isolated tissues at various stages of maturation and maternal nutrition during late gestation.", "content": "The availability and utilization of B-hydroxybutyrate as an alternate oxidative fuel during fasting hypoglycemia has been examined in the rat conceptus at 18 and 20 days gestation. A 48-hr maternal fast between days 16 and 18 or 18 and 20 resulted in a 50% fall in fetal glucose levels and a marked rise in B-hydroxybutyrate, i.e., 30-fold at 18 and 60-fold at 20 days. Tissue concentrations of B-hydroxybutyrate or acetoacetate did not exceed extracellular levels. Placenta, fetal brain, carcass, and liver all oxidized 14C-labeled B-hydroxybutyrate to 14CO2 when incubated in vitro in the presence of B-hydroxybutyrate. Highest rates of oxidation were apparent in the placenta, followed by brain, liver, and carcass. The D isomer of B-hydroxybutyrate appeared to be oxidized preferentially by all tissues studied. Despite levels of 3-ketoacid CoA transferase and acetoacetyl CoA thiolase lower at 18 than at 20 days, rates of oxidation in individual tissues incubated under identical concentrations of substrate were similar at both times. In liver and brain, increasing rates of 14CO2 generation proportionate to graded concentrations of B-hydroxybutyrate in vitro indicated that such rates were probably determined by substrate availability. B-hydroxybutyrate oxidation in extrahepatic fetal tissues was unaffected by maternal fasting. By contrast, fetal liver derived from fasted mothers generated significantly less 14CO2 from B-hydroxybutyrate than livers from fed mothers. It has been suggested that capabilities for ketone utilization are widespread in tissues of the conceptus, and that such utilization may fulfill in part the oxidative demands for continued anabolic growth during fasting hypoglycemia in the mother.", "contents": "Fetal fuels. I. Utilization of ketones by isolated tissues at various stages of maturation and maternal nutrition during late gestation. The availability and utilization of B-hydroxybutyrate as an alternate oxidative fuel during fasting hypoglycemia has been examined in the rat conceptus at 18 and 20 days gestation. A 48-hr maternal fast between days 16 and 18 or 18 and 20 resulted in a 50% fall in fetal glucose levels and a marked rise in B-hydroxybutyrate, i.e., 30-fold at 18 and 60-fold at 20 days. Tissue concentrations of B-hydroxybutyrate or acetoacetate did not exceed extracellular levels. Placenta, fetal brain, carcass, and liver all oxidized 14C-labeled B-hydroxybutyrate to 14CO2 when incubated in vitro in the presence of B-hydroxybutyrate. Highest rates of oxidation were apparent in the placenta, followed by brain, liver, and carcass. The D isomer of B-hydroxybutyrate appeared to be oxidized preferentially by all tissues studied. Despite levels of 3-ketoacid CoA transferase and acetoacetyl CoA thiolase lower at 18 than at 20 days, rates of oxidation in individual tissues incubated under identical concentrations of substrate were similar at both times. In liver and brain, increasing rates of 14CO2 generation proportionate to graded concentrations of B-hydroxybutyrate in vitro indicated that such rates were probably determined by substrate availability. B-hydroxybutyrate oxidation in extrahepatic fetal tissues was unaffected by maternal fasting. By contrast, fetal liver derived from fasted mothers generated significantly less 14CO2 from B-hydroxybutyrate than livers from fed mothers. It has been suggested that capabilities for ketone utilization are widespread in tissues of the conceptus, and that such utilization may fulfill in part the oxidative demands for continued anabolic growth during fasting hypoglycemia in the mother."}
{"id": "PMID:16196", "title": "Studies on the toxin of Aspergillus fumigatus. VII. Purification and some properities of hemolytic toxin (asp-hemolysin) from culture filtrates and mycelia.", "content": "A hemolytic toxin has been obtained from mycelia and culture filtrates of Aspergillus fumigatus by the procedures that included precipitation with ammonium sulfate, chromatography of DEAE-Sephadex, affinity chromatography on Concanavalin A-Sepharose and gell filtration on Sephadex G-50, G-100 AND G-150. The purified homolytic toxin was homogeneous on immunological and disk electrophoretic analysis, and the toxin from culture filtrates was identical with that from mycelia by the immunodiffusion technique. The hemolytic toxin was obtained for the first time from fungi and designated as Asp-hemolysin. The molecular weight of Asp-hemolysin was estimated to be appoximately 30,000 by the gel-filtration technique and its isoelectric point was found to be around pH 4.0. This Asp-hemolysin contained large amounts of protein and very small amounts of carbohydrate. The UV absorption spectrum of Asp-hemolysin showed a maximum absorption at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm, E 1% 1CM, was 12.4 and the ratio of absorbance at 280 nm to that at 260 nm was 2.3. The optimum pH for the hemolytic activity of the toxin toward chicken erythrocytes was 5.0 at room temperature and it was active in the pH range of 3.5 to 10.5. The optimum temperature was 21 C and about 50% of the activity was lost by incubation at 50 C for 5 min or 45 C for 23 min. The hemolytic activity was remarkably inhibited by Hg2+, Cu2+, Fe2+, Ag1+, iodine and p-CMB, but enhanced slightly by Zn2+ and Co2+.", "contents": "Studies on the toxin of Aspergillus fumigatus. VII. Purification and some properities of hemolytic toxin (asp-hemolysin) from culture filtrates and mycelia. A hemolytic toxin has been obtained from mycelia and culture filtrates of Aspergillus fumigatus by the procedures that included precipitation with ammonium sulfate, chromatography of DEAE-Sephadex, affinity chromatography on Concanavalin A-Sepharose and gell filtration on Sephadex G-50, G-100 AND G-150. The purified homolytic toxin was homogeneous on immunological and disk electrophoretic analysis, and the toxin from culture filtrates was identical with that from mycelia by the immunodiffusion technique. The hemolytic toxin was obtained for the first time from fungi and designated as Asp-hemolysin. The molecular weight of Asp-hemolysin was estimated to be appoximately 30,000 by the gel-filtration technique and its isoelectric point was found to be around pH 4.0. This Asp-hemolysin contained large amounts of protein and very small amounts of carbohydrate. The UV absorption spectrum of Asp-hemolysin showed a maximum absorption at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm and minimum absorption at 251 nm. The extinction coefficient at 280 nm, E 1% 1CM, was 12.4 and the ratio of absorbance at 280 nm to that at 260 nm was 2.3. The optimum pH for the hemolytic activity of the toxin toward chicken erythrocytes was 5.0 at room temperature and it was active in the pH range of 3.5 to 10.5. The optimum temperature was 21 C and about 50% of the activity was lost by incubation at 50 C for 5 min or 45 C for 23 min. The hemolytic activity was remarkably inhibited by Hg2+, Cu2+, Fe2+, Ag1+, iodine and p-CMB, but enhanced slightly by Zn2+ and Co2+."}
{"id": "PMID:16197", "title": "Resistance mechanism of chloramphenicol in Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis.", "content": "The chloramphenicol resistance of Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis isolated from clinical materials was proved to be due to an inactivating enzyme produced by these bacteria. The inactivated products of chloramphenicol were identified as 1-acetoxy, 3-acetoxy and 1,3-diacetoxy derivatives by thin-layer chromatography and infrared spectroscopy. The responsible enzyme was thus confirmed to be chloramphenicol acetyltransferase. The enzyme was inducible. It was partially purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and gel filtration on Sephadex G-150. The enzymes obtained from S. haemolyticus, S. pneumoniae and S. faecalis have been compared with the conclusion that they are identical with respect to molecular weight (approximately 75,000-80,000), optimum pH and heat stability.", "contents": "Resistance mechanism of chloramphenicol in Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis. The chloramphenicol resistance of Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis isolated from clinical materials was proved to be due to an inactivating enzyme produced by these bacteria. The inactivated products of chloramphenicol were identified as 1-acetoxy, 3-acetoxy and 1,3-diacetoxy derivatives by thin-layer chromatography and infrared spectroscopy. The responsible enzyme was thus confirmed to be chloramphenicol acetyltransferase. The enzyme was inducible. It was partially purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and gel filtration on Sephadex G-150. The enzymes obtained from S. haemolyticus, S. pneumoniae and S. faecalis have been compared with the conclusion that they are identical with respect to molecular weight (approximately 75,000-80,000), optimum pH and heat stability."}
{"id": "PMID:16198", "title": "[Physiologo-biochemical properties of a chemostatic culture of Bacillus megaterium at different pH values].", "content": "Properties of the chemostat culture of Bacillus megaterium were studied during its growth in the state of stress caused by unfavourable acid and alkaline values of pH. The effect of pH is not specific since changes occur in both energy exchange and constructive metabolism. The common action of hydrogen and hydroxyl ions is a decrease in the economic coefficient as greater amounts of the energy substrate are being used, the repression of oxidative enzymes, a decrease in the pool of ATP, and an increase in the respiration quotient. Protein synthesis is inhibited and synthesis of nitrogenless reserve substances is stimulated. Acid and alkaline conditions have also a specific action in the cells of Bac. megaterium. In the alkaline medium, metabolites are liberated into the medium, the cells are enriched with carbohydrates, and acetate is accumulated in the medium. In the acid medium, the cells are enriched with acid insoluble polyphosphates. Idle consumption of the energy substrate takes place.", "contents": "[Physiologo-biochemical properties of a chemostatic culture of Bacillus megaterium at different pH values]. Properties of the chemostat culture of Bacillus megaterium were studied during its growth in the state of stress caused by unfavourable acid and alkaline values of pH. The effect of pH is not specific since changes occur in both energy exchange and constructive metabolism. The common action of hydrogen and hydroxyl ions is a decrease in the economic coefficient as greater amounts of the energy substrate are being used, the repression of oxidative enzymes, a decrease in the pool of ATP, and an increase in the respiration quotient. Protein synthesis is inhibited and synthesis of nitrogenless reserve substances is stimulated. Acid and alkaline conditions have also a specific action in the cells of Bac. megaterium. In the alkaline medium, metabolites are liberated into the medium, the cells are enriched with carbohydrates, and acetate is accumulated in the medium. In the acid medium, the cells are enriched with acid insoluble polyphosphates. Idle consumption of the energy substrate takes place."}
{"id": "PMID:16203", "title": "Cimetidine in the treatment of duodenal ulcer.", "content": "In a double-blind trial performed in two centres, 67 outpatients with endoscopically confirmed duodenal (55) or pyloric canal (12) ulcers received cimetidine (34 patients) or placebo (33 patients) for six weeks. At 6 weeks complete healing of ulcers was significantly increased in patients receiving cimetidine (82%) compared with those receiving placebo (39%) (chi2=11-27; P less than 0-0008). Patients receiving cimetidine had significantly less daytime pain and required less antacid than those receiving placebo. Gastric acid secretion measured one week after cessation of treatment demonstrated that there was no rebound hypersecretion of acid in patients who had received cimetidine. The pretrial basal acid output of those patients whose ulcers failed to heal during cimetidine therapy was significantly greater than that of those whose ulcers healed during treatment with the drug (P less than 0-001). No side effects were encountered.", "contents": "Cimetidine in the treatment of duodenal ulcer. In a double-blind trial performed in two centres, 67 outpatients with endoscopically confirmed duodenal (55) or pyloric canal (12) ulcers received cimetidine (34 patients) or placebo (33 patients) for six weeks. At 6 weeks complete healing of ulcers was significantly increased in patients receiving cimetidine (82%) compared with those receiving placebo (39%) (chi2=11-27; P less than 0-0008). Patients receiving cimetidine had significantly less daytime pain and required less antacid than those receiving placebo. Gastric acid secretion measured one week after cessation of treatment demonstrated that there was no rebound hypersecretion of acid in patients who had received cimetidine. The pretrial basal acid output of those patients whose ulcers failed to heal during cimetidine therapy was significantly greater than that of those whose ulcers healed during treatment with the drug (P less than 0-001). No side effects were encountered."}
{"id": "PMID:16199", "title": "[Methanol oxidation by the NAD-specific dehydrogenase of methane-assimilating yeasts].", "content": "The activity of NAD-specific dehydrogenase (NAD-DH) capable of methanol oxidation was found in cell-free extracts of methanol assimilating yeast cultures Pichia pinus and Candida boidinii. The optimum pH of the incubation mixture for the enzyme is 7.8--7.9; the value of Km of the enzyme for methanol is 1.4-10(-4) M in P. pinus and 1.04-10(-3) M in C. boidinii. NAD-DH is absent from the cells cultivated on glucose, and is induced with growth on a medium containing methanol.", "contents": "[Methanol oxidation by the NAD-specific dehydrogenase of methane-assimilating yeasts]. The activity of NAD-specific dehydrogenase (NAD-DH) capable of methanol oxidation was found in cell-free extracts of methanol assimilating yeast cultures Pichia pinus and Candida boidinii. The optimum pH of the incubation mixture for the enzyme is 7.8--7.9; the value of Km of the enzyme for methanol is 1.4-10(-4) M in P. pinus and 1.04-10(-3) M in C. boidinii. NAD-DH is absent from the cells cultivated on glucose, and is induced with growth on a medium containing methanol."}
{"id": "PMID:16201", "title": "[Properties of the hexulose phosphate synthase of methylotrophic yeasts and bacteria].", "content": "Properties of hexulose phosphate synthase (HPS) were studied in extracts of the methanol assimilating yeast Candida methylica and the bacterium Arthrobacter globiformis B-175 assimilating methylated amines. HPS is an inducible enzyme which is localized in the soluble fraction of the cells. The effect of the pH of the reaction mixture, temperature, metal ions, and the concentration of substrates on the activity of HPS was studied. Properties of the enzyme were different in the yeast and the bacterium. The activity of HPS was strongly stimulated by ATP in C. methylica and was not affected in A. globiformis.", "contents": "[Properties of the hexulose phosphate synthase of methylotrophic yeasts and bacteria]. Properties of hexulose phosphate synthase (HPS) were studied in extracts of the methanol assimilating yeast Candida methylica and the bacterium Arthrobacter globiformis B-175 assimilating methylated amines. HPS is an inducible enzyme which is localized in the soluble fraction of the cells. The effect of the pH of the reaction mixture, temperature, metal ions, and the concentration of substrates on the activity of HPS was studied. Properties of the enzyme were different in the yeast and the bacterium. The activity of HPS was strongly stimulated by ATP in C. methylica and was not affected in A. globiformis."}
{"id": "PMID:16202", "title": "A study of cancer of the breast with special reference to its causation and prevention.", "content": "Breast feeding, lactational histories, parity, age at marriage, and socio-economic status were compared in 24 patients with carcinoma of breast, 24 healthy controls, and 48 patients suffering from other diseases. They were matched for age, social class and work or trade of the husbands. Breast cancer patients married later, had shorter lactational histories and had fewer children as compared with controls. Studies in six healthy mothers showed that milk became more alkaline on stasis in the breast. This study confirms the view that breast feeding protects against breast cancer. It suggests that one carcinogenic factor may be an alkaline milieu produced by the statis of milk in the breasts. An alkaline milieu surrounding epithelial surfaces produces cell proliferation and a marked increase in mitotic activity which may eventually lead to metaplasia and neoplasia.", "contents": "A study of cancer of the breast with special reference to its causation and prevention. Breast feeding, lactational histories, parity, age at marriage, and socio-economic status were compared in 24 patients with carcinoma of breast, 24 healthy controls, and 48 patients suffering from other diseases. They were matched for age, social class and work or trade of the husbands. Breast cancer patients married later, had shorter lactational histories and had fewer children as compared with controls. Studies in six healthy mothers showed that milk became more alkaline on stasis in the breast. This study confirms the view that breast feeding protects against breast cancer. It suggests that one carcinogenic factor may be an alkaline milieu produced by the statis of milk in the breasts. An alkaline milieu surrounding epithelial surfaces produces cell proliferation and a marked increase in mitotic activity which may eventually lead to metaplasia and neoplasia."}
{"id": "PMID:16209", "title": "[Cogans's syndrome in childhood (author's transl)].", "content": "A case--report is given of a patient with Cogan's syndrome in childhood. This syndrome consists of non-syphilitic interstitial keratitis and vestibuloauditory symptoms. Visual loss is rare but hearing loss is rapidly progressive. A relation to autoimmune diseases especially to panarteriitis nodosa has been suggested by a number of authors.", "contents": "[Cogans's syndrome in childhood (author's transl)]. A case--report is given of a patient with Cogan's syndrome in childhood. This syndrome consists of non-syphilitic interstitial keratitis and vestibuloauditory symptoms. Visual loss is rare but hearing loss is rapidly progressive. A relation to autoimmune diseases especially to panarteriitis nodosa has been suggested by a number of authors."}
{"id": "PMID:16212", "title": "Enzyme replacement therapy of exocrine pancreatic insufficiency in man. Relations between in vitro enzyme activities and in vivo potency in commercial pancreatic extracts.", "content": "I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1 +/- 9 per cent and 48.6 +/- 10 per cent (mean +/- S.E.M.) respectively, P less than 0.001. Enteric-coated tablets were less effective (20 +/- 13 per cent reduction, P greater than 0.02). The longer the gastric pH remained greater than or equal to 4 (r = 0.915, P less than 0.01) and the higher the average duodenal pH (r = 0.966, P less than 0.01), the more marked the reduction in steatorrhea.", "contents": "Enzyme replacement therapy of exocrine pancreatic insufficiency in man. Relations between in vitro enzyme activities and in vivo potency in commercial pancreatic extracts. I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1 +/- 9 per cent and 48.6 +/- 10 per cent (mean +/- S.E.M.) respectively, P less than 0.001. Enteric-coated tablets were less effective (20 +/- 13 per cent reduction, P greater than 0.02). The longer the gastric pH remained greater than or equal to 4 (r = 0.915, P less than 0.01) and the higher the average duodenal pH (r = 0.966, P less than 0.01), the more marked the reduction in steatorrhea."}
{"id": "PMID:16210", "title": "A possible histochemical mechanism of dihydrofolate reductase reaction.", "content": "The authors propose a hypothesis concerning the mechanism of dihydrofolate reductase reaction, suggesting a combined action of transhydrogenases and diaphorase particularly for this enzyme activity, and generally for the reductases.", "contents": "A possible histochemical mechanism of dihydrofolate reductase reaction. The authors propose a hypothesis concerning the mechanism of dihydrofolate reductase reaction, suggesting a combined action of transhydrogenases and diaphorase particularly for this enzyme activity, and generally for the reductases."}
{"id": "PMID:16213", "title": "Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules.", "content": "To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it.", "contents": "Fate of orally ingested enzymes in pancreatic insufficiency. Comparison of two dosage schedules. To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it."}
{"id": "PMID:16215", "title": "[Determination of riboflavin in foods].", "content": "The author examined the conditions under which the lumiflavin method may be used for the determination of riboflavin. Neither the presence of various cations and anions, nor the presence of cellulose, starch and protein exerted any effect on the oxidation with potassium permanganate. The riboflavin losses increased when potassium permanganate was used at a concentration of more than 2%. The losses were considerably lower it the purification of the extracts by means of potassium permanganate was performed after photolysis. The most favourable results were obtained when the extracts were shaken with chloroform prior to photolysis to eliminate interfering substances. These findings were corroborated by comparative analyses on 3 standard samples.", "contents": "[Determination of riboflavin in foods]. The author examined the conditions under which the lumiflavin method may be used for the determination of riboflavin. Neither the presence of various cations and anions, nor the presence of cellulose, starch and protein exerted any effect on the oxidation with potassium permanganate. The riboflavin losses increased when potassium permanganate was used at a concentration of more than 2%. The losses were considerably lower it the purification of the extracts by means of potassium permanganate was performed after photolysis. The most favourable results were obtained when the extracts were shaken with chloroform prior to photolysis to eliminate interfering substances. These findings were corroborated by comparative analyses on 3 standard samples."}
{"id": "PMID:16219", "title": "Comparative neutron small-angle scattering study of small spherical RNA viruses.", "content": "Small-angle neutron scattering from solutions of small RNA viruses has been used to study protein-nucleic acid organisation. In the five viruses investigated the RNA is confined to a sphere of about 100 A radius, with a central hole (with one possible exception). The interpenetration of RNA and protein varies with viruses and seems to be related to the natrue of the forces stabilising the virus.", "contents": "Comparative neutron small-angle scattering study of small spherical RNA viruses. Small-angle neutron scattering from solutions of small RNA viruses has been used to study protein-nucleic acid organisation. In the five viruses investigated the RNA is confined to a sphere of about 100 A radius, with a central hole (with one possible exception). The interpenetration of RNA and protein varies with viruses and seems to be related to the natrue of the forces stabilising the virus."}
{"id": "PMID:16224", "title": "Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum.", "content": "The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1 - 1 micronM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect. The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM apomorphine. Apomorphine itself had no significant effect on 3H-DA release. Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS.", "contents": "Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum. The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1 - 1 micronM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect. The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 micronM haloperidol on 3H-DA release could be blocked by 10 micronM cocaine, but not with 1 micronM apomorphine. Apomorphine itself had no significant effect on 3H-DA release. Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS."}
{"id": "PMID:16229", "title": "[Quantitative relationship between neurons of a different mediator nature in the motor nuclei of the cat spinal cord cervical thickening].", "content": "A histochemical analysis of the neuronal composition of the motor nuclei was performed on the cat cervical spinal cord. Motoneurons were distinguished by the location of AChE in the perinuclear space, on the membranes of the granular reticulum, on the axolemma, neurofilaments and neurotubuli, in the synaptosomes and the synaptic cleft; this evidences for the perinuclear synthesis of this enzyme and its transport within the axoplasm. Their amount reached 40-65% of the whole neuronal population. AChE identification together with autoradiographic tracing of glycine showed that large cholinergic motoneurons are accompanied by small glycine-accumulating neurons with short processes which form axo-somatic and axo-dendritic contacts with large neurons. The cholinergic motoneurons have polyreceptive properties, as can be concluded from the presence of AChE and glycine-containing terminals on their soma and processes, as well as some noradrenergic and serotoninergic and many unidentified terminals.", "contents": "[Quantitative relationship between neurons of a different mediator nature in the motor nuclei of the cat spinal cord cervical thickening]. A histochemical analysis of the neuronal composition of the motor nuclei was performed on the cat cervical spinal cord. Motoneurons were distinguished by the location of AChE in the perinuclear space, on the membranes of the granular reticulum, on the axolemma, neurofilaments and neurotubuli, in the synaptosomes and the synaptic cleft; this evidences for the perinuclear synthesis of this enzyme and its transport within the axoplasm. Their amount reached 40-65% of the whole neuronal population. AChE identification together with autoradiographic tracing of glycine showed that large cholinergic motoneurons are accompanied by small glycine-accumulating neurons with short processes which form axo-somatic and axo-dendritic contacts with large neurons. The cholinergic motoneurons have polyreceptive properties, as can be concluded from the presence of AChE and glycine-containing terminals on their soma and processes, as well as some noradrenergic and serotoninergic and many unidentified terminals."}
{"id": "PMID:16232", "title": "Salivary levels of anticonvulsants: a practical approach to drug monitoring.", "content": "Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent  (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal.", "contents": "Salivary levels of anticonvulsants: a practical approach to drug monitoring. Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent  (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal."}
{"id": "PMID:16235", "title": "[Guide to the automated calculation of acid-base equilibrium].", "content": "The sequence of calculations that can be entered in the memory of a desk computer for the automatic calculation of acid base balance parameters using data obtained with Astrup's tonometric method is described. A statistical comparison is also made between manually obtained results and those obtained with computer assistance. For clinical purposes the comparison is satisfactory.", "contents": "[Guide to the automated calculation of acid-base equilibrium]. The sequence of calculations that can be entered in the memory of a desk computer for the automatic calculation of acid base balance parameters using data obtained with Astrup's tonometric method is described. A statistical comparison is also made between manually obtained results and those obtained with computer assistance. For clinical purposes the comparison is satisfactory."}
{"id": "PMID:16240", "title": "Cataract and gamma-glutamyl cycle in myotonic dystrophy.", "content": "Gamma-Glutamyl transpeptidase (gamma-GT) may be responsible for the rapid catabolism and low levels of lenticular glutathione often associated with cataract formation. Elevated levels of serum gamma-GT in patients with myotonic dystrophy suggest that since the defect could be present in all tissues it might be responsible for the cataracts frequently observed in this genetic disease.", "contents": "Cataract and gamma-glutamyl cycle in myotonic dystrophy. Gamma-Glutamyl transpeptidase (gamma-GT) may be responsible for the rapid catabolism and low levels of lenticular glutathione often associated with cataract formation. Elevated levels of serum gamma-GT in patients with myotonic dystrophy suggest that since the defect could be present in all tissues it might be responsible for the cataracts frequently observed in this genetic disease."}
{"id": "PMID:16242", "title": "Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan.", "content": "We reviewed available clinical and pathologic autopsy material from 20 patients with infantile periarteritis nodosa with coronary artery involvement (IPN) from the continental United States, two Hawaiian patients with fatal mucocutaneous lymph node syndrome (MCLS; Kawasaki disease), and three patients with classical periarteritis nodosa (CPN). Comparison of the findings in patients with IPN and in patients with MCLS from Hawaii to material from patients with fatal MCLS from Japan showed no definite clinical reason to distinguish IPN from MCLS; neither gross nor microscopic features of the vascular lesions nor their pattern of distribution appears to warrant separation of IPN from fatal MCLS. CPN differs, both clinically and pathologically, from IPN/MCLS, and may well have a different etiology.", "contents": "Are infantile periarteritis nodosa with coronary artery involvement and fatal mucocutaneous lymph node syndrome the same? Comparison of 20 patients from North America with patients from Hawaii and Japan. We reviewed available clinical and pathologic autopsy material from 20 patients with infantile periarteritis nodosa with coronary artery involvement (IPN) from the continental United States, two Hawaiian patients with fatal mucocutaneous lymph node syndrome (MCLS; Kawasaki disease), and three patients with classical periarteritis nodosa (CPN). Comparison of the findings in patients with IPN and in patients with MCLS from Hawaii to material from patients with fatal MCLS from Japan showed no definite clinical reason to distinguish IPN from MCLS; neither gross nor microscopic features of the vascular lesions nor their pattern of distribution appears to warrant separation of IPN from fatal MCLS. CPN differs, both clinically and pathologically, from IPN/MCLS, and may well have a different etiology."}
{"id": "PMID:16244", "title": "[Variation of plasma amino acids in severe hepatitis with encephalopathy 10 cases].", "content": "Plasma levels of different amino acids were observed in 10 patients with severe hepatitis, 9 viral in origin and 1 toxic, over the course of the disease. There would appear to be a close relationship between the onset of encephalopathy and the appearance of a particular pattern in plasma amino acid equilibrium, characterised by a significant fall in the molar ratio existing between ramified amino acids (valine, leucine, isoleucine) and aromatic amino acids (phenylalanine and tyrosine). The role of these disturbances in the physiopathology of the encephalopathy and their effects on the synthesis of normal neurotransmitters and the intracerebral accumulation of false neurotransmitters is discussed.", "contents": "[Variation of plasma amino acids in severe hepatitis with encephalopathy 10 cases]. Plasma levels of different amino acids were observed in 10 patients with severe hepatitis, 9 viral in origin and 1 toxic, over the course of the disease. There would appear to be a close relationship between the onset of encephalopathy and the appearance of a particular pattern in plasma amino acid equilibrium, characterised by a significant fall in the molar ratio existing between ramified amino acids (valine, leucine, isoleucine) and aromatic amino acids (phenylalanine and tyrosine). The role of these disturbances in the physiopathology of the encephalopathy and their effects on the synthesis of normal neurotransmitters and the intracerebral accumulation of false neurotransmitters is discussed."}
{"id": "PMID:16252", "title": "Analgesic action of alpha-adrenolytics in albino mice.", "content": "The effect of alpha-adrenolytics: phenoxybenzamine, phentolamine, aceperone, dihydroegotamine, and yohimbine, was tested on reactivity to pain, and on the analgesic action of morphine and pethidine in albino mice. The compounds exert an analgesic effect by themselves, and potentiate the analgesic action of threshold doses of morphine and pethidine. The results seem to provide another proof that the cerbral noradrenaline neurons participate in central mechanisms of pain perception.", "contents": "Analgesic action of alpha-adrenolytics in albino mice. The effect of alpha-adrenolytics: phenoxybenzamine, phentolamine, aceperone, dihydroegotamine, and yohimbine, was tested on reactivity to pain, and on the analgesic action of morphine and pethidine in albino mice. The compounds exert an analgesic effect by themselves, and potentiate the analgesic action of threshold doses of morphine and pethidine. The results seem to provide another proof that the cerbral noradrenaline neurons participate in central mechanisms of pain perception."}
{"id": "PMID:16256", "title": "The different effects of sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin in man.", "content": "The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs.", "contents": "The different effects of sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin in man. The influence of oral sodium bicarbonate and aluminium hydroxide on the absorption of indomethacin has been studied in normal volunteers. While sodium bicarbonate appeared to increase indomethacin absorption, aluminium hydroxide markedly reduced both the rate and extent of absorption. The buccal absorption of indomethacin over the pH range 5-9 was also studied in normal volunteers, and showed that the percentage absorption increased markedly as the pH was reduced. The clinical importance both of pH-partition and of adsorption are discussed in the context of antacid interactions. It is concluded that caution must be exercised when prescribing an antacid with other orally-administered drugs."}
{"id": "PMID:16253", "title": "Factors which might modify analgesic effect of morphine in differentially housed rats.", "content": "The analgesic effect of morphine was studied by tail compression method in grouped and chronically isolated Wistar male rats developing muricide behavior showed increased pain threshold whilst indifferent (non-killer) showed reduced responses to the analgesic action of morphine. \"Natural\" killer (housed in groups) showed, on the other hand, increased sensitivity to morphine. The role of factors such as isolation period, behavioral pattern and contact with the victim was discussed.", "contents": "Factors which might modify analgesic effect of morphine in differentially housed rats. The analgesic effect of morphine was studied by tail compression method in grouped and chronically isolated Wistar male rats developing muricide behavior showed increased pain threshold whilst indifferent (non-killer) showed reduced responses to the analgesic action of morphine. \"Natural\" killer (housed in groups) showed, on the other hand, increased sensitivity to morphine. The role of factors such as isolation period, behavioral pattern and contact with the victim was discussed."}
{"id": "PMID:16254", "title": "Kinetics of drug decomposition. Part 46. Photooxidation and photolysis of some perazine derivatives.", "content": "The rate and type of the photochemical degradation of perazine derivatives in acidic aqueous solutions depends upon the nature of the substituent at C2 atom. Free perazine degrades by two parallel reactions, namely a fast reversible first-order photooxidation and a slow zero-order photolysis. An introduction of the substituent in the C2 position results frequently in the elimination of one of these reactions.", "contents": "Kinetics of drug decomposition. Part 46. Photooxidation and photolysis of some perazine derivatives. The rate and type of the photochemical degradation of perazine derivatives in acidic aqueous solutions depends upon the nature of the substituent at C2 atom. Free perazine degrades by two parallel reactions, namely a fast reversible first-order photooxidation and a slow zero-order photolysis. An introduction of the substituent in the C2 position results frequently in the elimination of one of these reactions."}
{"id": "PMID:16255", "title": "Kinetics of drug decomposition. Part 47. Effect of substituents on photochemical stability of perazine derivatives.", "content": "A quantum yield phi of photooxidation of perazine derivatives estimated actinometrically and the pKa, values were used for the correlation with the substituent volumes. The Hammett type plots of phi= f(sigma) and phi= f(pKa10--pKa1) are discussed.", "contents": "Kinetics of drug decomposition. Part 47. Effect of substituents on photochemical stability of perazine derivatives. A quantum yield phi of photooxidation of perazine derivatives estimated actinometrically and the pKa, values were used for the correlation with the substituent volumes. The Hammett type plots of phi= f(sigma) and phi= f(pKa10--pKa1) are discussed."}
{"id": "PMID:16259", "title": "Nitrogen-15 nuclear magnetic resonance of aliphatic tripeptides.", "content": "The 15N chemical shifts of eight aliphatic tripeptides have been measured at the natural-abundance level. For a given tripeptide, the resonances of the COOH-terminal and NH2-terminal amino acids can be identified by measurements at low or high pH. The shifts of the NH2-terminal amino acid nitrogens are essentially independent of the amino acids in the rest of the peptide. The shifts of the other nitrogens are characteristic of the amino acids themselves and of the immediately preceding amino acid toward the NH2 terminus. Non-terminal amide nitrogens have shifts of about 6 ppm upfield of COOH-terminal amide nitrogens at the isoelectric point of measurement. 15N chemical shifts appear to have considerable potential value for peptide sequencing.", "contents": "Nitrogen-15 nuclear magnetic resonance of aliphatic tripeptides. The 15N chemical shifts of eight aliphatic tripeptides have been measured at the natural-abundance level. For a given tripeptide, the resonances of the COOH-terminal and NH2-terminal amino acids can be identified by measurements at low or high pH. The shifts of the NH2-terminal amino acid nitrogens are essentially independent of the amino acids in the rest of the peptide. The shifts of the other nitrogens are characteristic of the amino acids themselves and of the immediately preceding amino acid toward the NH2 terminus. Non-terminal amide nitrogens have shifts of about 6 ppm upfield of COOH-terminal amide nitrogens at the isoelectric point of measurement. 15N chemical shifts appear to have considerable potential value for peptide sequencing."}
{"id": "PMID:16260", "title": "Regulation of cholesterol synthesis in rat adrenal gland through coordinate control of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase activities.", "content": "The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase[mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], two sequential enzymes in the cholesterol biosynthetic pathway, were shown to be regulated coordinately in the adrenal gland of the rat. When the plasma cholesterol level was lowered by administration of 4-aminopyrazolopyrimidine, a treatment known to enhance cholesterol synthesis in the adrenal, synthase activity in the gland rose by 14- to 29-fold and reductase activity rose by 50- to 100-fold. The subsequent intravenous infusion of low density lipoprotein restored the plasma cholesterol level and suppressed synthase and reductase activities in parallel. The activities of adrenal 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase were also shown to exhibit a coordinate pattern of diurnal variation with peaks in both enzymes achieved at the mid-point of the dark cycle. The activity of adrenal acetoacetyl coenzyme A thiolase (acetyl CoA acetyltransferase; acetyl-CoA:acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the enzyme preceding the synthase in the cholesterol biosynthetic pathway, and the activity of adrenal mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), the enzyme following the reductase, were not enhanced by cholesterol deprivation, and neither exhibited a pattern of diurnal variation. The coordinate control of 3-hydroxy-3-methylglutaryl CoA synthase and reductase in rat adrenal gland provides a model system to study the biochemical mechanism for the regulation of cholesterol synthesis in a tissue that uses cholesterol for the synthesis of steroid hormones.", "contents": "Regulation of cholesterol synthesis in rat adrenal gland through coordinate control of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase activities. The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase[mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], two sequential enzymes in the cholesterol biosynthetic pathway, were shown to be regulated coordinately in the adrenal gland of the rat. When the plasma cholesterol level was lowered by administration of 4-aminopyrazolopyrimidine, a treatment known to enhance cholesterol synthesis in the adrenal, synthase activity in the gland rose by 14- to 29-fold and reductase activity rose by 50- to 100-fold. The subsequent intravenous infusion of low density lipoprotein restored the plasma cholesterol level and suppressed synthase and reductase activities in parallel. The activities of adrenal 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase were also shown to exhibit a coordinate pattern of diurnal variation with peaks in both enzymes achieved at the mid-point of the dark cycle. The activity of adrenal acetoacetyl coenzyme A thiolase (acetyl CoA acetyltransferase; acetyl-CoA:acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the enzyme preceding the synthase in the cholesterol biosynthetic pathway, and the activity of adrenal mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), the enzyme following the reductase, were not enhanced by cholesterol deprivation, and neither exhibited a pattern of diurnal variation. The coordinate control of 3-hydroxy-3-methylglutaryl CoA synthase and reductase in rat adrenal gland provides a model system to study the biochemical mechanism for the regulation of cholesterol synthesis in a tissue that uses cholesterol for the synthesis of steroid hormones."}
{"id": "PMID:16261", "title": "Cell wall extension in Nitella as influenced by acids and ions.", "content": "The giant internode cells of Nitella axillaris exhibit acid-induced growth similar to that found in higher plants. The threshold pH is 4.5, with a maximum at 3.5. The acid growth effect is transient, lasting no more than 32 min. Extensibility measurements of isolated cell walls showed a similar pattern of acid enhancement. Prolonged boiling in water (12 hr) only partially inhibited the acid-induced wall extensibility and actually increased the extensibility at pH 6. It was concluded that physical, rather than enzymatic, processes were responsible for acid-enhanced continuous extension (\"creep\") in Nitella walls. A complex cation-sensitive mechanism that affects extensibility was also characterized. Among the stimulatory (wall-softening) cations, divalents were generally more effective than monovalents, with magnesium being the most stimulatory. The inhibitory (wall-hardening) cations included divalents and trivalents, aluminum being the most inhibitory. Ionic effects on extensibility were even less sensitive to prolonged boiling in water than acid effects.", "contents": "Cell wall extension in Nitella as influenced by acids and ions. The giant internode cells of Nitella axillaris exhibit acid-induced growth similar to that found in higher plants. The threshold pH is 4.5, with a maximum at 3.5. The acid growth effect is transient, lasting no more than 32 min. Extensibility measurements of isolated cell walls showed a similar pattern of acid enhancement. Prolonged boiling in water (12 hr) only partially inhibited the acid-induced wall extensibility and actually increased the extensibility at pH 6. It was concluded that physical, rather than enzymatic, processes were responsible for acid-enhanced continuous extension (\"creep\") in Nitella walls. A complex cation-sensitive mechanism that affects extensibility was also characterized. Among the stimulatory (wall-softening) cations, divalents were generally more effective than monovalents, with magnesium being the most stimulatory. The inhibitory (wall-hardening) cations included divalents and trivalents, aluminum being the most inhibitory. Ionic effects on extensibility were even less sensitive to prolonged boiling in water than acid effects."}
{"id": "PMID:16262", "title": "The product of a newly identified gene, gInF, is required for synthesis of glutamine synthetase in Salmonella.", "content": "The product of a newly identified gene, glnF, which is distinct from the glutamine synthetase structural gene (glnA), is required for synthesis of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2[ in Salmonella typhimurium and probably in Escherichia coli. Salmonella strains with ICR (2-chloro-6-methoxy-9-[3-(2-chloroethyl)aminopropylamino]acridine dihyodrochloride)-induced (frameshift) mutations in glnF are glutamine auxotrophs; they have less than 10% oof wild-type glutamine synthetase activity or antigen and are unable to derepress the synthesis of the enzyme. The mutant allele is recessive to the wild-type allele, indicating that the glnF gene encodes a diffusible product. Mutant glnF strains have normal activities of all proteins involved in covalent modification of glutamine synthetase: adenylyltransferase (EC 2.7.7.42), PII, uridylyltransferase, and uridylyl removing enzyme. In addition, they have glutamate synthase (EC 1.4.1.13) and glutamate dehydrogenase (EC 1.4.1.4) activities. Thus, glnF does not encode the structure of any of these proteins. The above evidence suggests that the product of the glnF gene is (or produces) a positive regulatory factor that is required for synthesis of glutamine synthetase; it indicates that auto-regulation cannot account for control of the synthesis of glutamine synthetase in Salmonella.", "contents": "The product of a newly identified gene, gInF, is required for synthesis of glutamine synthetase in Salmonella. The product of a newly identified gene, glnF, which is distinct from the glutamine synthetase structural gene (glnA), is required for synthesis of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2[ in Salmonella typhimurium and probably in Escherichia coli. Salmonella strains with ICR (2-chloro-6-methoxy-9-[3-(2-chloroethyl)aminopropylamino]acridine dihyodrochloride)-induced (frameshift) mutations in glnF are glutamine auxotrophs; they have less than 10% oof wild-type glutamine synthetase activity or antigen and are unable to derepress the synthesis of the enzyme. The mutant allele is recessive to the wild-type allele, indicating that the glnF gene encodes a diffusible product. Mutant glnF strains have normal activities of all proteins involved in covalent modification of glutamine synthetase: adenylyltransferase (EC 2.7.7.42), PII, uridylyltransferase, and uridylyl removing enzyme. In addition, they have glutamate synthase (EC 1.4.1.13) and glutamate dehydrogenase (EC 1.4.1.4) activities. Thus, glnF does not encode the structure of any of these proteins. The above evidence suggests that the product of the glnF gene is (or produces) a positive regulatory factor that is required for synthesis of glutamine synthetase; it indicates that auto-regulation cannot account for control of the synthesis of glutamine synthetase in Salmonella."}
{"id": "PMID:16279", "title": "Synthesis of certain benzo- and pyridodiazepines likely to possess tranquilizing effect.", "content": "The synthesis of certain 1.5-benzodiazepinediones, some of their oxygen-free analogues and a number of the 7-nitro derivatives is described. Condensation of 3.4-diaminopyridine with diethylmalonate instead of affording the expected pyridodiazepine, yielded an imidazopyridine, the structure of which was inferred from spectral data Nevertheless, the pyridodiazepine was obtained by condensing the diamino-heterocycle with malonyl dichloride.", "contents": "Synthesis of certain benzo- and pyridodiazepines likely to possess tranquilizing effect. The synthesis of certain 1.5-benzodiazepinediones, some of their oxygen-free analogues and a number of the 7-nitro derivatives is described. Condensation of 3.4-diaminopyridine with diethylmalonate instead of affording the expected pyridodiazepine, yielded an imidazopyridine, the structure of which was inferred from spectral data Nevertheless, the pyridodiazepine was obtained by condensing the diamino-heterocycle with malonyl dichloride."}
{"id": "PMID:16280", "title": "The biological fate of reserpine.", "content": "Orally administered reserpine is readily absorbed from the GI tract. During this process at least a portion of the drug is metabolized by the intestinal mucosa and then presumably is acted upon by serum esterases. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from the hydrolytic cleavage of reserpine. Since most of the blood leaving the GI tract passes through the liver via the portal vein, hepatic metabolism would also be expected to reduce reserpine levels in the blood. The relative contributions of serum esterases versus hepatic metabolism in the biotransformation of reserpine in vivo are not known. However, very little unmetabolized reserpine is eventually eliminated in the urine. In the liver, it is quite likely that both microsomal oxidative and hydrolytic enzymes contribute to the metabolism of reserpine. It seems that microsomal oxidation (such as the demethylation of the 4-methoxy group on the TMBA moiety) must precede hydrolysis since inhibition of demethylation markedly reduces the rate of hydrolysis. In addition to oxidation and hydrolysis, conjugative reactions also must occur in liver or extrahepatic tissues since both glucuronide and sulfate conjugates of TMBA have been identified. Some reserpine molecules do seem to escape metabolism, however, since significant amounts of intact reserpine have been found in fecal samples taken from both experimental animals and human beings after either oral or parenteral drug administration. Presumably reserpine is transported from the blood via the biliary tree into the small intestine where it is either reabsorbed or eliminated in the feces. Pulmonary elimination of CO2 produced after complete oxidation of the 4-methoxy group of TMBA has also been shown to occur both in vivo and in vitro. The following may serve as a model for the relationship between the subcellular distribution of reserpine and its site of action. After a single intravenous injection most of the reserpine, probably loosely bound to plasma albumin, is distributed to tissues on the basis of their blood flow. Because of its lipophilic properties, reserpine would easily penetrate cell membranes and then bind possibly electrostatically to intracellular membrane components, particularly those rich in phospholipids. Much of the circulating reserpine would then either be metabolized or be taken up by the lipid depots of the body, leading to a rapid redistribution of the reversibly bound reserpine from the tissues. During this time a relatively small fraction of the total reserpine administered by injection would become associated with monoaminergic granular membranes in a more specific and irreversible manner. This would result in a persistent, nonstoichiometric inhibition of monoamine uptake. Such a small specific binding would not be detectable for at least 18 hr after reserpine administration, i.e., until most of the reversibly bound alkaloid had been metabolized and/or excreted...", "contents": "The biological fate of reserpine. Orally administered reserpine is readily absorbed from the GI tract. During this process at least a portion of the drug is metabolized by the intestinal mucosa and then presumably is acted upon by serum esterases. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from the hydrolytic cleavage of reserpine. Since most of the blood leaving the GI tract passes through the liver via the portal vein, hepatic metabolism would also be expected to reduce reserpine levels in the blood. The relative contributions of serum esterases versus hepatic metabolism in the biotransformation of reserpine in vivo are not known. However, very little unmetabolized reserpine is eventually eliminated in the urine. In the liver, it is quite likely that both microsomal oxidative and hydrolytic enzymes contribute to the metabolism of reserpine. It seems that microsomal oxidation (such as the demethylation of the 4-methoxy group on the TMBA moiety) must precede hydrolysis since inhibition of demethylation markedly reduces the rate of hydrolysis. In addition to oxidation and hydrolysis, conjugative reactions also must occur in liver or extrahepatic tissues since both glucuronide and sulfate conjugates of TMBA have been identified. Some reserpine molecules do seem to escape metabolism, however, since significant amounts of intact reserpine have been found in fecal samples taken from both experimental animals and human beings after either oral or parenteral drug administration. Presumably reserpine is transported from the blood via the biliary tree into the small intestine where it is either reabsorbed or eliminated in the feces. Pulmonary elimination of CO2 produced after complete oxidation of the 4-methoxy group of TMBA has also been shown to occur both in vivo and in vitro. The following may serve as a model for the relationship between the subcellular distribution of reserpine and its site of action. After a single intravenous injection most of the reserpine, probably loosely bound to plasma albumin, is distributed to tissues on the basis of their blood flow. Because of its lipophilic properties, reserpine would easily penetrate cell membranes and then bind possibly electrostatically to intracellular membrane components, particularly those rich in phospholipids. Much of the circulating reserpine would then either be metabolized or be taken up by the lipid depots of the body, leading to a rapid redistribution of the reversibly bound reserpine from the tissues. During this time a relatively small fraction of the total reserpine administered by injection would become associated with monoaminergic granular membranes in a more specific and irreversible manner. This would result in a persistent, nonstoichiometric inhibition of monoamine uptake. Such a small specific binding would not be detectable for at least 18 hr after reserpine administration, i.e., until most of the reversibly bound alkaloid had been metabolized and/or excreted..."}
{"id": "PMID:16283", "title": "Meiosis in perspective.", "content": "Our understanding of meiosis springs from two suggestions made by Weismann in 1887. One was that meiosis would be found to compensate for fertilization in the life cycles of both sexes and all organisms. The other was that the development of sexual reproduction in evolution depended on the value of meiosis in exposing the results of genetic recombination to natural selection. In confirming these propositions we were bound to discover that the properties of meiosis appear both as the causes and the consequences of evolution: it is the hinge on which turns the evolution of breeding method, reproductive habit, life cycle and hereditary structure, that is the genetic system, in all sexually reproducing species of organism. We have had three main fields of attack on our problem. First, there was the natural variation of meiosis including that of two-track hereditary within the species: here, animals took the lead. Secondly, there was the experimental field - both with genetic controls such as polyploidy and the sterilizing mutations of mitosis as well as meiosis, and with physical and chemical controls: here, the higher plants and micro-organisms have given us our great opportunities. Thirdly, we have the widening field where physicochemical knowledge and genetic control converge and collaborate. In all this work we have to be aware that meiosis works with chromosomes which always have the two functions of accomplishing evolution and of implementing its results in heredity. In consequence, the adaptation of meiosis is perpetually imperfect.", "contents": "Meiosis in perspective. Our understanding of meiosis springs from two suggestions made by Weismann in 1887. One was that meiosis would be found to compensate for fertilization in the life cycles of both sexes and all organisms. The other was that the development of sexual reproduction in evolution depended on the value of meiosis in exposing the results of genetic recombination to natural selection. In confirming these propositions we were bound to discover that the properties of meiosis appear both as the causes and the consequences of evolution: it is the hinge on which turns the evolution of breeding method, reproductive habit, life cycle and hereditary structure, that is the genetic system, in all sexually reproducing species of organism. We have had three main fields of attack on our problem. First, there was the natural variation of meiosis including that of two-track hereditary within the species: here, animals took the lead. Secondly, there was the experimental field - both with genetic controls such as polyploidy and the sterilizing mutations of mitosis as well as meiosis, and with physical and chemical controls: here, the higher plants and micro-organisms have given us our great opportunities. Thirdly, we have the widening field where physicochemical knowledge and genetic control converge and collaborate. In all this work we have to be aware that meiosis works with chromosomes which always have the two functions of accomplishing evolution and of implementing its results in heredity. In consequence, the adaptation of meiosis is perpetually imperfect."}
{"id": "PMID:16284", "title": "A first view of the meiotic process.", "content": "In this introductory paper we have highlighted some aspects of the meiotic process which seem important to us and about which some especially interesting features have been discovered. These include the switch from mitosis to meiosis, premeiotic DNA synthesis, association of the chromosomes with the synaptonemal complex, the nature of chromosome homology in relation to chromosome pairing, the process of chromosome pairing, the regulation of meiosis as a developmental process and the process of recombination. We have indulged in speculation in the hope that it will stimulate additional discussion and research into these crucial meiotic cell divisions which link the generations in higher organisms.", "contents": "A first view of the meiotic process. In this introductory paper we have highlighted some aspects of the meiotic process which seem important to us and about which some especially interesting features have been discovered. These include the switch from mitosis to meiosis, premeiotic DNA synthesis, association of the chromosomes with the synaptonemal complex, the nature of chromosome homology in relation to chromosome pairing, the process of chromosome pairing, the regulation of meiosis as a developmental process and the process of recombination. We have indulged in speculation in the hope that it will stimulate additional discussion and research into these crucial meiotic cell divisions which link the generations in higher organisms."}
{"id": "PMID:16285", "title": "The time and duration of meiosis.", "content": "Ever since meiosis was recognized as a process there has been a continuing interest in its temporal aspects. Two main types of meiotic timing experiments have been conducted: first, experiments to estimate the duration of meiosis (and sometimes its stages); second, experiments to locate the sensitive stage(s) when exposure of meiocytes to various treatments can affect meiotic chromosome behaviour (e.g. pairing or recombination). Such experiments have played an important role in increasing our understanding of the meiotic process. The duration of meiosis has been estimated in about 70 organisms, including two prokaryotes (yeast and Chlamydomonas) and the following eukaryotes: 1 Basidiomycete (Coprinus lagopus), 2 Gymnosperms (Larix decidua and Thuja plicata gracilis). at least 39 angiosperms, and at least 26 animal species. The duration of female meiosis has been estimated in far fewer species than male meiosis. However, estimates of the duration of female meiosis are available for 6 angiosperms. Drosophila melanogaster, Xenopus laevis, and several mammals. Comparison of these data shows that the duration of meiosis is one of the most variable aspects of the meiotic process, ranging from less than 6 h in yeast to more than 40 years in the human female. Developmental holds at different stages of meiosis are common in plants and animals, and inevitably prolong the meiotic division. However, even among species without developmental holds, the duration of meiosis is very variable. For instance, in animals it ranges from about 1-2 days in male Drosophila melanogaster to more than 24 days in male Homo sapiens and several Orthopterans. Despite the large variation in the duration of meiosis three generalizations can be made: (i) first prophase is always very long compared with the remaining meiotic stages, (ii) the rate of meiotic development is very slow compared with the rate of development in dividing somatic meristem cells of the same organisms under  the same conditions, (iii) the duration of meiosis is characteristic of the genotype and species. Four main factors have been recognized which effect or determine the duration of meiosis, namely (1) environmental factors (e.g. temperature); (2) nuclear DNA content; (3) ploidy level of the organism; and, (4) the genotype. Because nuclear DNA content plays a major role in determining the duration of meiosis, it has been suggested that DNA influences the rate of meiotic development in two ways: first through its informational content (the genotype), and second indirectly by the physical and mechanical effects of its mass independently of its informational content (i.e. the nucleotype). Thus, the observed duration of meiosis is the result of a complex genotype-nucleotype-environment interaction. With the obvious exception of variation caused by developmental holds, changes in the duration of meiosis usually involve proportional changes in the durations of all its stages...", "contents": "The time and duration of meiosis. Ever since meiosis was recognized as a process there has been a continuing interest in its temporal aspects. Two main types of meiotic timing experiments have been conducted: first, experiments to estimate the duration of meiosis (and sometimes its stages); second, experiments to locate the sensitive stage(s) when exposure of meiocytes to various treatments can affect meiotic chromosome behaviour (e.g. pairing or recombination). Such experiments have played an important role in increasing our understanding of the meiotic process. The duration of meiosis has been estimated in about 70 organisms, including two prokaryotes (yeast and Chlamydomonas) and the following eukaryotes: 1 Basidiomycete (Coprinus lagopus), 2 Gymnosperms (Larix decidua and Thuja plicata gracilis). at least 39 angiosperms, and at least 26 animal species. The duration of female meiosis has been estimated in far fewer species than male meiosis. However, estimates of the duration of female meiosis are available for 6 angiosperms. Drosophila melanogaster, Xenopus laevis, and several mammals. Comparison of these data shows that the duration of meiosis is one of the most variable aspects of the meiotic process, ranging from less than 6 h in yeast to more than 40 years in the human female. Developmental holds at different stages of meiosis are common in plants and animals, and inevitably prolong the meiotic division. However, even among species without developmental holds, the duration of meiosis is very variable. For instance, in animals it ranges from about 1-2 days in male Drosophila melanogaster to more than 24 days in male Homo sapiens and several Orthopterans. Despite the large variation in the duration of meiosis three generalizations can be made: (i) first prophase is always very long compared with the remaining meiotic stages, (ii) the rate of meiotic development is very slow compared with the rate of development in dividing somatic meristem cells of the same organisms under  the same conditions, (iii) the duration of meiosis is characteristic of the genotype and species. Four main factors have been recognized which effect or determine the duration of meiosis, namely (1) environmental factors (e.g. temperature); (2) nuclear DNA content; (3) ploidy level of the organism; and, (4) the genotype. Because nuclear DNA content plays a major role in determining the duration of meiosis, it has been suggested that DNA influences the rate of meiotic development in two ways: first through its informational content (the genotype), and second indirectly by the physical and mechanical effects of its mass independently of its informational content (i.e. the nucleotype). Thus, the observed duration of meiosis is the result of a complex genotype-nucleotype-environment interaction. With the obvious exception of variation caused by developmental holds, changes in the duration of meiosis usually involve proportional changes in the durations of all its stages..."}
{"id": "PMID:16286", "title": "Recombination in male and female meiocytes contrasted.", "content": "For technical reasons studies of chiasma frequency and distribution, and hence of intrachromosomal recombination, have mostly been confined to male meiosis. However, there is now sufficient comparative data on male and female meiosis, in both plants and animals, to show that the extent of intra-chromosomal recombination in some organisms may be much the same on the female as on the male side, whereas other organisms show extreme sexual divergence in this regard. The evolutionary significance of such diversity remains enigmatic.", "contents": "Recombination in male and female meiocytes contrasted. For technical reasons studies of chiasma frequency and distribution, and hence of intrachromosomal recombination, have mostly been confined to male meiosis. However, there is now sufficient comparative data on male and female meiosis, in both plants and animals, to show that the extent of intra-chromosomal recombination in some organisms may be much the same on the female as on the male side, whereas other organisms show extreme sexual divergence in this regard. The evolutionary significance of such diversity remains enigmatic."}
{"id": "PMID:16287", "title": "The assembly of the synaptinemal complex.", "content": "The assembly of the synaptinemal complex in the ascomycete Neottiella was studied by three-dimensional reconstruction of a late zygotene nucleus. A single banded lateral component is formed between the two sister chromatids of each homologous chromosome prior to their pairing. The central regions are pre-assembled in organized form in folds of the granular part of the nucleolus and then converted into an amorphous transport form. The latter appears to move through the nucleoplasm to sites between the lateral components of synapsing homologous chromosomes. The central region material is reorganized into blocks with a recognizable central component and attached to one lateral component. The last step in the completion of the synaptinemal complex is the association of the free surface of the organized central region with the corresponding segment of the homologous lateral component. The findings are discussed in relation to mechanisms of chromosome pairing and chiasma formation.", "contents": "The assembly of the synaptinemal complex. The assembly of the synaptinemal complex in the ascomycete Neottiella was studied by three-dimensional reconstruction of a late zygotene nucleus. A single banded lateral component is formed between the two sister chromatids of each homologous chromosome prior to their pairing. The central regions are pre-assembled in organized form in folds of the granular part of the nucleolus and then converted into an amorphous transport form. The latter appears to move through the nucleoplasm to sites between the lateral components of synapsing homologous chromosomes. The central region material is reorganized into blocks with a recognizable central component and attached to one lateral component. The last step in the completion of the synaptinemal complex is the association of the free surface of the organized central region with the corresponding segment of the homologous lateral component. The findings are discussed in relation to mechanisms of chromosome pairing and chiasma formation."}
{"id": "PMID:16288", "title": "Homologous chromosome pairing.", "content": "Commonly accepted precepts are challenged: (1) that homologous chromosome pairing is normally mediated by nuclear envelope attachment sites; (2) that crossover site establishment awaits synaptic completion; and (3) that it is the function of the synaptonemal complex to hold homologues in register so that equal crossing over can occur, and perhaps to provide machinery for the crossover process. Although these views may eventually be shown to be true, it is felt that currently available evidence does not warrant their full acceptance, and that alternatives should be considered. As examples of alternatives the following ideas, with some supporting evidence, are suggested: (1) homologous chromosome pairing (in non-haplont organisms) may be accomplished by chance meeting of homologue segments (followed by establishment of invisible, elastic connectors) at congression for a mitotic metaphase (in many cases perhaps the premeiotic mitosis); (2) crossover sites may be established before, during, or immediately following initiation of synapsis; and (3) the synaptonemal complex may somehow function in the crossover process at the inception of its formation, but its complete deployment throughout each normal bivalent may serve some other role, such as mediation of the binding of sister chromatids apparently required for chiasma maintenance until anaphase I.", "contents": "Homologous chromosome pairing. Commonly accepted precepts are challenged: (1) that homologous chromosome pairing is normally mediated by nuclear envelope attachment sites; (2) that crossover site establishment awaits synaptic completion; and (3) that it is the function of the synaptonemal complex to hold homologues in register so that equal crossing over can occur, and perhaps to provide machinery for the crossover process. Although these views may eventually be shown to be true, it is felt that currently available evidence does not warrant their full acceptance, and that alternatives should be considered. As examples of alternatives the following ideas, with some supporting evidence, are suggested: (1) homologous chromosome pairing (in non-haplont organisms) may be accomplished by chance meeting of homologue segments (followed by establishment of invisible, elastic connectors) at congression for a mitotic metaphase (in many cases perhaps the premeiotic mitosis); (2) crossover sites may be established before, during, or immediately following initiation of synapsis; and (3) the synaptonemal complex may somehow function in the crossover process at the inception of its formation, but its complete deployment throughout each normal bivalent may serve some other role, such as mediation of the binding of sister chromatids apparently required for chiasma maintenance until anaphase I."}
{"id": "PMID:16289", "title": "Some morphological aspects of the synaptonemal complex in higher plants.", "content": "The synaptonemal complex is illustrated in electron micrographs from pollen mother cells (p.m.cs) of the following plants: Fritillaria lanceolata, Allium fistulosum, Tulbaghia violacea, Luzula purpurea, Phaedranassa viridiflora and the tulip cultivar Keiserkroon. The possibility that the lateral elements in synaptonemal complexes of plants are tubiform structures is discussed in relation to their fine structure and in the light of a deformity seen in them. An assessment of the evidence suggesting that both lateral and central elements in the complex are ribonucleoprotein structures is made. The effect of brief water treatment on the chromatin and synaptonemal complex at zygotene in p.m.cs of the Phaedranassa is discussed, particularly with reference to two precisely oriented axial strands then seen running between the lateral elements. Examination of stages of premeiotic interphase and early leptotene in p.m.cs of the Fritillaria, revealed that the axial cores laid down at leptotene are formed first in heterochromatic regions, which in this species are locked in chromocentres that persist until pachytene. Further, at leptotene the chromatin in these parts was singularly more decondensed (diffuse) than at any other period, including the premeiotic interphase, subsequent stages of meiosis and mitotic cycle in meristems. It is suggested that the diffuse state of the chromatin in chromocentres at the onset of leptotene, allows the necessary freedom of movement required to promote homologous pairing of the heterochromatic segments. Evidence of such a movement was indicated by a change in position of the nucleoli, which moved from a more central position at early premeiotic interphase to a peripheral one at the onset of leptotene, when they are seen adpressed to the nuclear envelope.", "contents": "Some morphological aspects of the synaptonemal complex in higher plants. The synaptonemal complex is illustrated in electron micrographs from pollen mother cells (p.m.cs) of the following plants: Fritillaria lanceolata, Allium fistulosum, Tulbaghia violacea, Luzula purpurea, Phaedranassa viridiflora and the tulip cultivar Keiserkroon. The possibility that the lateral elements in synaptonemal complexes of plants are tubiform structures is discussed in relation to their fine structure and in the light of a deformity seen in them. An assessment of the evidence suggesting that both lateral and central elements in the complex are ribonucleoprotein structures is made. The effect of brief water treatment on the chromatin and synaptonemal complex at zygotene in p.m.cs of the Phaedranassa is discussed, particularly with reference to two precisely oriented axial strands then seen running between the lateral elements. Examination of stages of premeiotic interphase and early leptotene in p.m.cs of the Fritillaria, revealed that the axial cores laid down at leptotene are formed first in heterochromatic regions, which in this species are locked in chromocentres that persist until pachytene. Further, at leptotene the chromatin in these parts was singularly more decondensed (diffuse) than at any other period, including the premeiotic interphase, subsequent stages of meiosis and mitotic cycle in meristems. It is suggested that the diffuse state of the chromatin in chromocentres at the onset of leptotene, allows the necessary freedom of movement required to promote homologous pairing of the heterochromatic segments. Evidence of such a movement was indicated by a change in position of the nucleoli, which moved from a more central position at early premeiotic interphase to a peripheral one at the onset of leptotene, when they are seen adpressed to the nuclear envelope."}
{"id": "PMID:16290", "title": "Chromosome distribution: experiments on cell hybrids and in vitro.", "content": "Ostergren (1951) provided a simple explanation for both chromosome distribution in mitosis and chromosome segregation in meiosis, and more recently a molecular extension of his hypothesis has been possible. This report focuses on experimental tests of these ideas. Micromanipulation experiments on cell hybrids containing both meiotic and mitotic spindles demonstrate that differences in meiotic and mitotic chromosome behavior are determined by something intrinsic to the chromosome: meiotic chromosomes transferred to a mitotic spindle (or vice versa) behave just as they normally would. The molecular explanation postulates polarized growth or binding of microtubules at kinetochores. This has just been tested in vitro by McGill & Brinkley (1975) and by Telzer, Moses & Rosenbaum (1975), and their results are reviewed. In addition, a novel method for in vitro studies is described - mechanical demembranation of cells which is compatible with quite normal chromosome movement in anaphase. After addition of microtubule subunits to a demembranated prophase cell, chromosome orientation and movement toward an aster was observed for the first time in vitro. It is concluded that important aspects of chromosome distribution are probably understood at both the cellular and molecular levels, but final tests are still required. The outlook is hopeful indeed because the gaps in our knowledge are well known - the necessity of observations on prophase is a recurrent theme - and the means of filling the gaps are in hand.", "contents": "Chromosome distribution: experiments on cell hybrids and in vitro. Ostergren (1951) provided a simple explanation for both chromosome distribution in mitosis and chromosome segregation in meiosis, and more recently a molecular extension of his hypothesis has been possible. This report focuses on experimental tests of these ideas. Micromanipulation experiments on cell hybrids containing both meiotic and mitotic spindles demonstrate that differences in meiotic and mitotic chromosome behavior are determined by something intrinsic to the chromosome: meiotic chromosomes transferred to a mitotic spindle (or vice versa) behave just as they normally would. The molecular explanation postulates polarized growth or binding of microtubules at kinetochores. This has just been tested in vitro by McGill & Brinkley (1975) and by Telzer, Moses & Rosenbaum (1975), and their results are reviewed. In addition, a novel method for in vitro studies is described - mechanical demembranation of cells which is compatible with quite normal chromosome movement in anaphase. After addition of microtubule subunits to a demembranated prophase cell, chromosome orientation and movement toward an aster was observed for the first time in vitro. It is concluded that important aspects of chromosome distribution are probably understood at both the cellular and molecular levels, but final tests are still required. The outlook is hopeful indeed because the gaps in our knowledge are well known - the necessity of observations on prophase is a recurrent theme - and the means of filling the gaps are in hand."}
{"id": "PMID:16291", "title": "Biochemistry of meiosis.", "content": "The process of meiosis in Lilium falls into four physiological stages - prezygotene, zygotene, pachytene, and post-pachytene. Each of these stages has distinctive metabolic characteristics. Commitment to meiosis occurs during the prezygotene interval at about the time when S-phase replication is completed. The activities following commitment are essential to synapsis inasmuch as perturbations of cells during that interval have subsequent effects on synapsis and crossing over. Just before the initiation of synapsis, a distinctive lipoprotein complex appears in the nucleus. The complex most probably functions in the process of pairing. Zygotene is marked by the delayed replication of specific intercalary segments of chromosomal DNA (Z-DNA), the replication being a necessary condition for ongoing synapsis. The replication occurs in the lipoprotein complex in the presence of a reassociation protein (r-protein). Z-DNA segments would appear to have other meiotic functions inasmuch as the replicated segments remain unligated to the body of chromosomal DNA until the beginning of chromosome disjunction. The pachytene interval is marked by an activation of endonucleolytic activity. The enzyme produces single-stranded nicks in the DNA at specific loci. These loci consist of moderately repeated segments; about 100-200 base pairs long. Extracellular agents, such as radiation, cause random nicking regardless of the meiotic stage at which they are applied. Localized nicking and repair are thus unique features of meiosis. The temporal segregation of metabolic activities concerned with pairing and crossing over and their operation in special chromosome regions constitute the most prominent features of the biochemical events associated with meiosis.", "contents": "Biochemistry of meiosis. The process of meiosis in Lilium falls into four physiological stages - prezygotene, zygotene, pachytene, and post-pachytene. Each of these stages has distinctive metabolic characteristics. Commitment to meiosis occurs during the prezygotene interval at about the time when S-phase replication is completed. The activities following commitment are essential to synapsis inasmuch as perturbations of cells during that interval have subsequent effects on synapsis and crossing over. Just before the initiation of synapsis, a distinctive lipoprotein complex appears in the nucleus. The complex most probably functions in the process of pairing. Zygotene is marked by the delayed replication of specific intercalary segments of chromosomal DNA (Z-DNA), the replication being a necessary condition for ongoing synapsis. The replication occurs in the lipoprotein complex in the presence of a reassociation protein (r-protein). Z-DNA segments would appear to have other meiotic functions inasmuch as the replicated segments remain unligated to the body of chromosomal DNA until the beginning of chromosome disjunction. The pachytene interval is marked by an activation of endonucleolytic activity. The enzyme produces single-stranded nicks in the DNA at specific loci. These loci consist of moderately repeated segments; about 100-200 base pairs long. Extracellular agents, such as radiation, cause random nicking regardless of the meiotic stage at which they are applied. Localized nicking and repair are thus unique features of meiosis. The temporal segregation of metabolic activities concerned with pairing and crossing over and their operation in special chromosome regions constitute the most prominent features of the biochemical events associated with meiosis."}
{"id": "PMID:16292", "title": "The genetic analysis of meiosis in female Drosophila melanogaster.", "content": "The three major features of meiosis are first synapsis, then exchange, and finally, disjunction of homologous chromosomes; these phenomena occur before pachytene, during pachytene, and after pachytene respectively. The effects of meiotic mutants, or other perturbations, either endogenous or exogenous, on the meiotic process may be assigned tentatively to one of these intervals, based on the earliest discernible abnormality. Thus mutants exhibiting abnormal disjunction and normal exchange affect post-pachytene functions; mutants exhibiting abnormal disjunction and exchange but with ultrastructurally normal appearing synaptonemal complex affect pachytene functions; and mutants with abnormal disjunction, exchange, and synaptonemal complex affect prepachytene functions. This rationale is applied to the temporal seriation of effects of meiotic mutants and chromosomal abnormalities on the meiotic programme.", "contents": "The genetic analysis of meiosis in female Drosophila melanogaster. The three major features of meiosis are first synapsis, then exchange, and finally, disjunction of homologous chromosomes; these phenomena occur before pachytene, during pachytene, and after pachytene respectively. The effects of meiotic mutants, or other perturbations, either endogenous or exogenous, on the meiotic process may be assigned tentatively to one of these intervals, based on the earliest discernible abnormality. Thus mutants exhibiting abnormal disjunction and normal exchange affect post-pachytene functions; mutants exhibiting abnormal disjunction and exchange but with ultrastructurally normal appearing synaptonemal complex affect pachytene functions; and mutants with abnormal disjunction, exchange, and synaptonemal complex affect prepachytene functions. This rationale is applied to the temporal seriation of effects of meiotic mutants and chromosomal abnormalities on the meiotic programme."}
{"id": "PMID:16293", "title": "Inferences from genetical evidence on the course of meiotic chromosome pairing in plants.", "content": "Meiotic chromosome pairing is a process that is amenable to genetic and experimental analysis. The combined use of these two approaches allows for the process to be dissected into several finite periods of time in which the developmental stages of pairing can be precisely located. Evidence is now available, in particular in plants, that shows that the pairing of homologous chromosomes, as observed at metaphase I, is affected by events occurring as early as the last premeiotic mitosis; and that the maintenance of this early determined state is subsequently maintained by constituents (presumably proteins) that are sensitive to either colchicine, temperature or gene control. A critical assessment of this evidence in wheat and a comparison of the process of pairing in wheat with the course of meiotic pairing in other plants and animals is presented.", "contents": "Inferences from genetical evidence on the course of meiotic chromosome pairing in plants. Meiotic chromosome pairing is a process that is amenable to genetic and experimental analysis. The combined use of these two approaches allows for the process to be dissected into several finite periods of time in which the developmental stages of pairing can be precisely located. Evidence is now available, in particular in plants, that shows that the pairing of homologous chromosomes, as observed at metaphase I, is affected by events occurring as early as the last premeiotic mitosis; and that the maintenance of this early determined state is subsequently maintained by constituents (presumably proteins) that are sensitive to either colchicine, temperature or gene control. A critical assessment of this evidence in wheat and a comparison of the process of pairing in wheat with the course of meiotic pairing in other plants and animals is presented."}
{"id": "PMID:16294", "title": "Ribosomes, membranes and organelles during meiosis in angiosperms.", "content": "Evidence is presented from both observational and analytical techniques indicating profound changes to take place in the ribosome population during male and female meiosis in some flowering plants. During microsporogenesis these appear to involve the elimination of the major part of the ribosome complement early in the meiotic prophase, and its subsequent restoration by the disintegration in the tetrad cytoplasm of 'nucleoloids', themselves synthesized in the nucleus during late prophase. In female tissue the process is essentially similar except for differences in the restoration of the ribosome population. Immediately before the eradication of the ribosomes in both sexes, a sizeable proportion of the meiocyte cytoplasm is encapsulated by double, or multiple unit membrane profiles. Significantly this cytoplasm remains unaffected by the agents responsible for the degredation of the ribosome population. These events are also reflected in the organelle populations where cycles of dedifferentiation and redifferentiation take place. In view of evidence from other organisms, it is considered unlikely that these cycles are in any way a prerequisite of meiosis, but more a characteristic of cells undergoing major changes of phase, where a cytoplasmic 'clean-up' is required before the next stage of growth may begin.", "contents": "Ribosomes, membranes and organelles during meiosis in angiosperms. Evidence is presented from both observational and analytical techniques indicating profound changes to take place in the ribosome population during male and female meiosis in some flowering plants. During microsporogenesis these appear to involve the elimination of the major part of the ribosome complement early in the meiotic prophase, and its subsequent restoration by the disintegration in the tetrad cytoplasm of 'nucleoloids', themselves synthesized in the nucleus during late prophase. In female tissue the process is essentially similar except for differences in the restoration of the ribosome population. Immediately before the eradication of the ribosomes in both sexes, a sizeable proportion of the meiocyte cytoplasm is encapsulated by double, or multiple unit membrane profiles. Significantly this cytoplasm remains unaffected by the agents responsible for the degredation of the ribosome population. These events are also reflected in the organelle populations where cycles of dedifferentiation and redifferentiation take place. In view of evidence from other organisms, it is considered unlikely that these cycles are in any way a prerequisite of meiosis, but more a characteristic of cells undergoing major changes of phase, where a cytoplasmic 'clean-up' is required before the next stage of growth may begin."}
{"id": "PMID:16295", "title": "Meiosis in Bombyx mori females.", "content": "Crossing over is absent in oocytes of the silkworm, Bombyx mori. Synaptonemal complexes are present during pachytene between the paired chromosomes. At leptotene, lateral components of the synaptonemal complex are attached in a bouquet to a limited region of the nuclear envelope. Before completion of lateral components, synaptonemal complex formation begins at the nuclear envelope. With synaptonemal complex formation proceeding from both ends bivalents occasionally become interlocked. After pairing is completed, the bouquet arrangement is dissolved possibly as a result of a flow of the inner membrane of the nuclear envelope thereby separating the telomeres. After the telomeres are released from the nuclear envelope, material is deposited onto the lateral components of the synaptonemal complex. The modified synaptonemal complexes are retained by the bivalents until metaphase I. It is suggested that these modified synaptonemal complexes substitute for chiasmata in order to ensure regular disjunction of homologous chromosomes in the absence of crossing over.", "contents": "Meiosis in Bombyx mori females. Crossing over is absent in oocytes of the silkworm, Bombyx mori. Synaptonemal complexes are present during pachytene between the paired chromosomes. At leptotene, lateral components of the synaptonemal complex are attached in a bouquet to a limited region of the nuclear envelope. Before completion of lateral components, synaptonemal complex formation begins at the nuclear envelope. With synaptonemal complex formation proceeding from both ends bivalents occasionally become interlocked. After pairing is completed, the bouquet arrangement is dissolved possibly as a result of a flow of the inner membrane of the nuclear envelope thereby separating the telomeres. After the telomeres are released from the nuclear envelope, material is deposited onto the lateral components of the synaptonemal complex. The modified synaptonemal complexes are retained by the bivalents until metaphase I. It is suggested that these modified synaptonemal complexes substitute for chiasmata in order to ensure regular disjunction of homologous chromosomes in the absence of crossing over."}
{"id": "PMID:16296", "title": "Meiosis in a temperature-sensitive DNA-synthesis mutant and in an apomictic yeast strain (Saccharomyces cerevisiae).", "content": "It is shown that in the temperature-sensitive yeast mutant (Saccharomyces cerevisiae) spo 11 at the restrictive temperature of 34 degrees C. (1) premeiotic DNA synthesis is nearly completely blocked; (2) the nucleus enters meiotic prophase indicated by the formation of axial cores and polysynaptonemal complexes; (3) the kinetic apparatus functions normally at meiosis I and II; (4) early spore formation occurs in nearly all cells but it is variable and all spores eventually degenerate. It is concluded that chromosome replication is not a prerequisite for the functions listed above. The apomictic yeast strain 4117 produces 2 diploid spores. It is shown that a diploid which produces 2-spored asci, synthesized from 4117, no. 5, and an adenine requiring strain (1) has a normal meiotic prophase with abundant synaptonemal complexes; (2) has only one meiotic spindle; (3) has spores which form red clones more frequently than normal or u.v.-treated vegetative cells form ade/ade red sectors through mitotic recombination. It is concluded that this apomictic yeast has maintained meiotic prophase, but that one of the two meiotic divisions is suppressed.", "contents": "Meiosis in a temperature-sensitive DNA-synthesis mutant and in an apomictic yeast strain (Saccharomyces cerevisiae). It is shown that in the temperature-sensitive yeast mutant (Saccharomyces cerevisiae) spo 11 at the restrictive temperature of 34 degrees C. (1) premeiotic DNA synthesis is nearly completely blocked; (2) the nucleus enters meiotic prophase indicated by the formation of axial cores and polysynaptonemal complexes; (3) the kinetic apparatus functions normally at meiosis I and II; (4) early spore formation occurs in nearly all cells but it is variable and all spores eventually degenerate. It is concluded that chromosome replication is not a prerequisite for the functions listed above. The apomictic yeast strain 4117 produces 2 diploid spores. It is shown that a diploid which produces 2-spored asci, synthesized from 4117, no. 5, and an adenine requiring strain (1) has a normal meiotic prophase with abundant synaptonemal complexes; (2) has only one meiotic spindle; (3) has spores which form red clones more frequently than normal or u.v.-treated vegetative cells form ade/ade red sectors through mitotic recombination. It is concluded that this apomictic yeast has maintained meiotic prophase, but that one of the two meiotic divisions is suppressed."}
{"id": "PMID:16297", "title": "Recombination and meiosis.", "content": "Although exchanges between sister chromatids are common in mitotic cells, those involving homologous chromosomes are rare. Since recombination between homologues is one of the functions of meiosis, it follows that one aspect of the differentiation of the meiocyte involves the synthesis of proteins or enzymes which facilitate synapsis and exchange. Mutants are known which seem to have constitutive levels of mitotic recombination between homologues, and these may be defective in the mechanism which normally represses mitotic recombination. It has been proposed that one component of the synaptonemal complex (s.c.) is a filamentous pairing protein with DNA binding sites which are base sequence specific. Synapsis occurs because the distribution of these sequences is the same in homologues. When only non-homologous chromosomes are present, as in haploid meiosis, only weak pairing can occur, since the base sequences are largely out of register. Although certain features of recombination at the molecular level are known, none of the models so far proposed suggest an explanation for interference between crossovers. It is suggested that interference may depend on the presence of a limited amount of another DNA binding protein which is specifically located within the s.c. A crossover between naked DNA molecules is initially a weak structure, which must be later converted into a visible and mechanically strong chiasma. It is assumed that this stabilization of a crossover is achieved by the DNA binding protein, which can diffuse freely within the s.c. and bind cooperatively to any recombinant DNA molecules within it. Depletion of the binding protein within the vicinity of a crossover makes it unlikely that the second crossover can be formed nearby.", "contents": "Recombination and meiosis. Although exchanges between sister chromatids are common in mitotic cells, those involving homologous chromosomes are rare. Since recombination between homologues is one of the functions of meiosis, it follows that one aspect of the differentiation of the meiocyte involves the synthesis of proteins or enzymes which facilitate synapsis and exchange. Mutants are known which seem to have constitutive levels of mitotic recombination between homologues, and these may be defective in the mechanism which normally represses mitotic recombination. It has been proposed that one component of the synaptonemal complex (s.c.) is a filamentous pairing protein with DNA binding sites which are base sequence specific. Synapsis occurs because the distribution of these sequences is the same in homologues. When only non-homologous chromosomes are present, as in haploid meiosis, only weak pairing can occur, since the base sequences are largely out of register. Although certain features of recombination at the molecular level are known, none of the models so far proposed suggest an explanation for interference between crossovers. It is suggested that interference may depend on the presence of a limited amount of another DNA binding protein which is specifically located within the s.c. A crossover between naked DNA molecules is initially a weak structure, which must be later converted into a visible and mechanically strong chiasma. It is assumed that this stabilization of a crossover is achieved by the DNA binding protein, which can diffuse freely within the s.c. and bind cooperatively to any recombinant DNA molecules within it. Depletion of the binding protein within the vicinity of a crossover makes it unlikely that the second crossover can be formed nearby."}
{"id": "PMID:16299", "title": "Variation in the spire index of some coiled gastropod shells, and its evolutionary significance.", "content": "The spire index (height/maximum diameter of shell) is a fairly adequate measure of the shape of the coiled shell of most terrestrial and freshwater gastropod shells but less so in complex marine shells with thorns, flanges and spouts. In this study, only adult free-crawling forms with several whorls, able to retract completely into the shell, are considered. In the Stylommatophora of the Western European terrestrial fauna the distribution of the spire index is markedly bimodal, the modes, with values of about 3 and about 0.5, corresponding respectively to shells with a high to very high spire (and small spire angle) and those varying from more or less globular or trochoid to very flattened and disk-like (spire angle from 60 degrees to 180 degrees). The same two modes are found in the taxonomically different terrestrial stylommatophorans of the U.S.A., and in the faunas of Puerto Rico (Caribbean) and New Caledonia (southwest Pacific). Basommatophorans also show two, rather different, modes. North American marine archaeogastropods are mainly equidimensional but with a few disk-like forms and a very few high-spired ones, marine mesogastropods are mainly high-spired but with disk-like forms, neogastropods high-spired, and relevant euthyneurans sharply bimodal, like the stylommatophorans. Fossil archaeogastropods of the Palaeozoic were much more various at first than modern forms. There is some indication that they became restricted in variety as caenogastropods became abundant, but also that the proportion of marine disk-like shells has decreased markedly since the Palaeozoic. Modes of h/d are characteristic of large taxonomic groups but not taxonomically restricted since given values may appear as specific, generic or subfamilial variants from a mode, and appear sporadically in unrelated forms. There is also no broad association between modal value and broad ecological characters. Since nearly all values do occur in some group or other, no mechanical requirement can be invoked to explain such variation. In the land Stylommatophora enough is known of the broad ecology to suggest that in extreme habitats species with very different size or shell-shape may occur together, and that generalized feeders with similar shells may show separation, ecological or geographical (but in that case, also ecological). Since different shapes of shell will have different mechanical characteristics when considered as burdens to be carried, it is suggested tentatively that they may be related to the positions in which different species normally walk and hence to their preferred feeding places. This would explain an apparent tendency for different taxonomic groups to occupy the same part of the scatter of h/d in different regions of the world, for many groups in the same region to occupy different portions of the scatter, and perhaps the apparent exclusion by caenogastropods of archaeogastropods from part of the scatter since the Palaeozoic. It is argued that the distributions discovered are explicable only by natural selection.", "contents": "Variation in the spire index of some coiled gastropod shells, and its evolutionary significance. The spire index (height/maximum diameter of shell) is a fairly adequate measure of the shape of the coiled shell of most terrestrial and freshwater gastropod shells but less so in complex marine shells with thorns, flanges and spouts. In this study, only adult free-crawling forms with several whorls, able to retract completely into the shell, are considered. In the Stylommatophora of the Western European terrestrial fauna the distribution of the spire index is markedly bimodal, the modes, with values of about 3 and about 0.5, corresponding respectively to shells with a high to very high spire (and small spire angle) and those varying from more or less globular or trochoid to very flattened and disk-like (spire angle from 60 degrees to 180 degrees). The same two modes are found in the taxonomically different terrestrial stylommatophorans of the U.S.A., and in the faunas of Puerto Rico (Caribbean) and New Caledonia (southwest Pacific). Basommatophorans also show two, rather different, modes. North American marine archaeogastropods are mainly equidimensional but with a few disk-like forms and a very few high-spired ones, marine mesogastropods are mainly high-spired but with disk-like forms, neogastropods high-spired, and relevant euthyneurans sharply bimodal, like the stylommatophorans. Fossil archaeogastropods of the Palaeozoic were much more various at first than modern forms. There is some indication that they became restricted in variety as caenogastropods became abundant, but also that the proportion of marine disk-like shells has decreased markedly since the Palaeozoic. Modes of h/d are characteristic of large taxonomic groups but not taxonomically restricted since given values may appear as specific, generic or subfamilial variants from a mode, and appear sporadically in unrelated forms. There is also no broad association between modal value and broad ecological characters. Since nearly all values do occur in some group or other, no mechanical requirement can be invoked to explain such variation. In the land Stylommatophora enough is known of the broad ecology to suggest that in extreme habitats species with very different size or shell-shape may occur together, and that generalized feeders with similar shells may show separation, ecological or geographical (but in that case, also ecological). Since different shapes of shell will have different mechanical characteristics when considered as burdens to be carried, it is suggested tentatively that they may be related to the positions in which different species normally walk and hence to their preferred feeding places. This would explain an apparent tendency for different taxonomic groups to occupy the same part of the scatter of h/d in different regions of the world, for many groups in the same region to occupy different portions of the scatter, and perhaps the apparent exclusion by caenogastropods of archaeogastropods from part of the scatter since the Palaeozoic. It is argued that the distributions discovered are explicable only by natural selection."}
{"id": "PMID:16301", "title": "Pigment epithelial ensheathment and phagocytosis of extrafoveal cones in human retina.", "content": "The association between extrafoveal cone outer segments and pigment epithelial cells was studied by transmission electron microscopy in three human retinas; ages 5,45 and 60. The pigment epithelial apical surface from a fourth human retina, age 38,was viewed in the scanning electron microscope. Multiple villous-like apical processes protrude from the pigment epithelium into the space above each cone. Sometimes one or more of these processes is sheet-like in form and contains a wealth of intracellular organelles, including mitochondria. One or more of the villous-like procesess reaches the cone and expands to ensheath the upper one-third of the outer segment. Llike vertebrate rods, extrafoveal human cones shed their terminal disks in packets and these packets are phagocytosed by the ensheathing apical processes. The phagosomes then ascend in the processes toward the pigment epithelia soma. Digestion of phagosomes appears to begin in the apical processes.", "contents": "Pigment epithelial ensheathment and phagocytosis of extrafoveal cones in human retina. The association between extrafoveal cone outer segments and pigment epithelial cells was studied by transmission electron microscopy in three human retinas; ages 5,45 and 60. The pigment epithelial apical surface from a fourth human retina, age 38,was viewed in the scanning electron microscope. Multiple villous-like apical processes protrude from the pigment epithelium into the space above each cone. Sometimes one or more of these processes is sheet-like in form and contains a wealth of intracellular organelles, including mitochondria. One or more of the villous-like procesess reaches the cone and expands to ensheath the upper one-third of the outer segment. Llike vertebrate rods, extrafoveal human cones shed their terminal disks in packets and these packets are phagocytosed by the ensheathing apical processes. The phagosomes then ascend in the processes toward the pigment epithelia soma. Digestion of phagosomes appears to begin in the apical processes."}
{"id": "PMID:16303", "title": "Relationship between neurotransmitters and atherosclerosis.", "content": "Dyslipemia and finally the producing of atherosclerosis signal some modulation disturbances in neurotransmitters by the onset of a permanent incapacity of the organism to coordinate the adapting mechanism against the over-high activity of stress factors. Neurotransmitters and related substances facilitate and modulate energy and information in biosystems, assigning an important role to central control as noradrenaline, serotonin and other biogenic amines mediate emotional stress.", "contents": "Relationship between neurotransmitters and atherosclerosis. Dyslipemia and finally the producing of atherosclerosis signal some modulation disturbances in neurotransmitters by the onset of a permanent incapacity of the organism to coordinate the adapting mechanism against the over-high activity of stress factors. Neurotransmitters and related substances facilitate and modulate energy and information in biosystems, assigning an important role to central control as noradrenaline, serotonin and other biogenic amines mediate emotional stress."}
{"id": "PMID:16313", "title": "[New views referred to gamma-glutamyl-transpeptidase (author's transl].", "content": "The AA. have observed some patients suffering from persistent chronic hepatitis, aggressive chronic hepatitis, severe virus hepatitis, hepatic cirrhosis, hepatic metastasis, cholecystolithiasis, hepatic abscess, congestic heart disorder, alcoholism also patients treated with barbiturics and benzodiazepine, comparising in the meanwhile gamma-glutamyl-transaminase. They would suggest a new interpretation: the observed enzyme was higher in the obstructive diseases, gamma-GT also notable higher in the cellular hepatic diseases (hepatitis, cirrhosis and so on). In their opinion gamma-GT should be a regular enzymatic screening for liver diseases, but should not anyway eliminate the till now used enzymes.", "contents": "[New views referred to gamma-glutamyl-transpeptidase (author's transl]. The AA. have observed some patients suffering from persistent chronic hepatitis, aggressive chronic hepatitis, severe virus hepatitis, hepatic cirrhosis, hepatic metastasis, cholecystolithiasis, hepatic abscess, congestic heart disorder, alcoholism also patients treated with barbiturics and benzodiazepine, comparising in the meanwhile gamma-glutamyl-transaminase. They would suggest a new interpretation: the observed enzyme was higher in the obstructive diseases, gamma-GT also notable higher in the cellular hepatic diseases (hepatitis, cirrhosis and so on). In their opinion gamma-GT should be a regular enzymatic screening for liver diseases, but should not anyway eliminate the till now used enzymes."}
{"id": "PMID:16319", "title": "Alpha-adrenergic blockers on ventricular automatism in rat heart.", "content": "The role of the alpha-adrenergic receptors in the genesis of cardiac arrhythmias induced in the isolated rat right ventricle has been studied. The administration of six alpha-adrenergic blocking agents (phenoxybenzamine, dibenamine, phentolamine, tolazoline, azapetine and SY-28) did not alter the automatism induced. Even when can not be excluded the existance of alpha-adrenergic receptors in the rat ventricle, it is clear that alpha-blocking drugs are ineffective to abolish the arrhythmias induced by an increase in the activity of the Purkinje fibers.", "contents": "Alpha-adrenergic blockers on ventricular automatism in rat heart. The role of the alpha-adrenergic receptors in the genesis of cardiac arrhythmias induced in the isolated rat right ventricle has been studied. The administration of six alpha-adrenergic blocking agents (phenoxybenzamine, dibenamine, phentolamine, tolazoline, azapetine and SY-28) did not alter the automatism induced. Even when can not be excluded the existance of alpha-adrenergic receptors in the rat ventricle, it is clear that alpha-blocking drugs are ineffective to abolish the arrhythmias induced by an increase in the activity of the Purkinje fibers."}
{"id": "PMID:16321", "title": "Cardiorespiratory and behavioral reactions to the lidocaine-induced convulsions in the dog.", "content": "Central nervous system (CNS) reactions to intermittently infused lidocaine HCl (i.v.) were evaluated from cardiorespiratory and behavioral responses in 33 mongrel dogs. Threshold convulsive doses were established for each of three distinct and predictable seizure patterns. The first seizure activity observed was tonic extension (TE) which occurred at an infused lidocaine dose of 12.2+/-0.6 mg/kg followed by running activity after 22.7+/-0.9 mg/kg lidocaine was given. The threshold for intermittent tonic-clonic seizures (ICS) occurred at an infused lidocaine dose of 33.3+/-1.5 mg/kg. Mean blood pressure and pulse pressure increased at the onset of TE and ICS, with a decline in arterial pH and PCO2 during the ICS. No relationship was found between the animals' acid-base status and the ICS threshold. Toxicity to lidocaine in the dog is expressed by distinct behavioral responses suggesting lidocaine may affect various parts of the CNS. The mongrel dog appears to be a satisfactory and simple model system to evaluate lidocaine toxicity from behavioral and cardiorespiratory responses.", "contents": "Cardiorespiratory and behavioral reactions to the lidocaine-induced convulsions in the dog. Central nervous system (CNS) reactions to intermittently infused lidocaine HCl (i.v.) were evaluated from cardiorespiratory and behavioral responses in 33 mongrel dogs. Threshold convulsive doses were established for each of three distinct and predictable seizure patterns. The first seizure activity observed was tonic extension (TE) which occurred at an infused lidocaine dose of 12.2+/-0.6 mg/kg followed by running activity after 22.7+/-0.9 mg/kg lidocaine was given. The threshold for intermittent tonic-clonic seizures (ICS) occurred at an infused lidocaine dose of 33.3+/-1.5 mg/kg. Mean blood pressure and pulse pressure increased at the onset of TE and ICS, with a decline in arterial pH and PCO2 during the ICS. No relationship was found between the animals' acid-base status and the ICS threshold. Toxicity to lidocaine in the dog is expressed by distinct behavioral responses suggesting lidocaine may affect various parts of the CNS. The mongrel dog appears to be a satisfactory and simple model system to evaluate lidocaine toxicity from behavioral and cardiorespiratory responses."}
{"id": "PMID:16322", "title": "Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine.", "content": "The inhibition by naloxone of tolerance and dependence in morphinized mice is dose- and time-dependent. In animals receiving a single, large dose of morphine, partial inhibition by naloxone of the analgesic effect results in partial development of tolerance and dependence. This relationship appears to be true for animals which have been treated with morphine chronically. Complete and sustained blockage of morphine receptors by naloxone is required for complete inhibition of the development of tolerance and dependence.", "contents": "Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine. The inhibition by naloxone of tolerance and dependence in morphinized mice is dose- and time-dependent. In animals receiving a single, large dose of morphine, partial inhibition by naloxone of the analgesic effect results in partial development of tolerance and dependence. This relationship appears to be true for animals which have been treated with morphine chronically. Complete and sustained blockage of morphine receptors by naloxone is required for complete inhibition of the development of tolerance and dependence."}
{"id": "PMID:16323", "title": "Exercise-induced bronchoconstriction in patients with bronchial asthma. Its prevention with an antihistaminic agent.", "content": "14 asthmatic patients developing regularly exercise-induced bronchoconstriction were subjected to a submaximal exercise on a bicycle ergometer. On the first day the exercise was not preceded by any medication; on the second, 50 mg thiazinamium was given, and on the third day 2 mg atropine was given before the exercise. The changes in the calibre of the bronchi were assessed with a Wright peak flow meter. With thiazinamium a complete protection against the bronchoconstriction was observed in 12 patients, in one the protection was partial and in an other no beneficial effect of the drug was found. It seems that protection given by thiazinamium was due to its antihistaminic property and not to the anticholinergic one, as among 10 patients protected by thiazinamium, only 2 were also protected by the atropine.", "contents": "Exercise-induced bronchoconstriction in patients with bronchial asthma. Its prevention with an antihistaminic agent. 14 asthmatic patients developing regularly exercise-induced bronchoconstriction were subjected to a submaximal exercise on a bicycle ergometer. On the first day the exercise was not preceded by any medication; on the second, 50 mg thiazinamium was given, and on the third day 2 mg atropine was given before the exercise. The changes in the calibre of the bronchi were assessed with a Wright peak flow meter. With thiazinamium a complete protection against the bronchoconstriction was observed in 12 patients, in one the protection was partial and in an other no beneficial effect of the drug was found. It seems that protection given by thiazinamium was due to its antihistaminic property and not to the anticholinergic one, as among 10 patients protected by thiazinamium, only 2 were also protected by the atropine."}
{"id": "PMID:16337", "title": "[Beta blocking agents in the treatment of algo-neuro-dystrophies. Apropos of 34 cases].", "content": "The authors report results of a series of thirty four cases of algo-neuro-dystrophy treated with beta blockers. This treatment produced favorable results in thirty out of the thirty four cases and the mode of action is discussed.", "contents": "[Beta blocking agents in the treatment of algo-neuro-dystrophies. Apropos of 34 cases]. The authors report results of a series of thirty four cases of algo-neuro-dystrophy treated with beta blockers. This treatment produced favorable results in thirty out of the thirty four cases and the mode of action is discussed."}
{"id": "PMID:16339", "title": "Comparison of rimiterol and terbutaline, given by aerosol, in a long-term study.", "content": "In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy.", "contents": "Comparison of rimiterol and terbutaline, given by aerosol, in a long-term study. In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy."}
{"id": "PMID:16340", "title": "[Vasculitis in hepatitis B infection].", "content": "Personal observations have confirmed the frequent association of HB-infection with certain forms of vasculitis. 4 of 11 patients with polyarteritis nodosa were repeatedly found to be HBs-Ag positive and had chronic hepatitis of varying severity. In patients with giant cell arteritis (polymyalgia rheumatica and temporal arteritis) anti-HBs was found more frequently than in controls, especially when examined within 6 months after onset of symptoms (7 of 20 equal 35% had anti-HBs, versus 6% of controls). Several lines of evidence point to the important role played by circulating HBs-Ag/anti-HBs complexes in the development of HB-associated vasculitis.", "contents": "[Vasculitis in hepatitis B infection]. Personal observations have confirmed the frequent association of HB-infection with certain forms of vasculitis. 4 of 11 patients with polyarteritis nodosa were repeatedly found to be HBs-Ag positive and had chronic hepatitis of varying severity. In patients with giant cell arteritis (polymyalgia rheumatica and temporal arteritis) anti-HBs was found more frequently than in controls, especially when examined within 6 months after onset of symptoms (7 of 20 equal 35% had anti-HBs, versus 6% of controls). Several lines of evidence point to the important role played by circulating HBs-Ag/anti-HBs complexes in the development of HB-associated vasculitis."}
{"id": "PMID:16336", "title": "[Role of neuropsychiatric pathology and pharmacology in neuroendocrinologic research].", "content": "Experimental, pharmacological and clinical data are presented suggesting that neurotransmitters, neurohormones and adenohypophyseal hormones have effects respectively on aterior pituitary and on the CNS. The related functional hypothesis are proposed and discussed.", "contents": "[Role of neuropsychiatric pathology and pharmacology in neuroendocrinologic research]. Experimental, pharmacological and clinical data are presented suggesting that neurotransmitters, neurohormones and adenohypophyseal hormones have effects respectively on aterior pituitary and on the CNS. The related functional hypothesis are proposed and discussed."}
{"id": "PMID:16343", "title": "Direct resorption of bone by human monocytes.", "content": "Cultured human peripheral blood monocytes stimulate the release of bone mineral and matrix from killed long bones of fetal rats. These effects were inhibited by cortisol but were not altered by hormones that normally stimulate osteoclastic bone resorption. There was no evidence of morphologic differentiation of the monocytes into osteoclasts during bone resorption.", "contents": "Direct resorption of bone by human monocytes. Cultured human peripheral blood monocytes stimulate the release of bone mineral and matrix from killed long bones of fetal rats. These effects were inhibited by cortisol but were not altered by hormones that normally stimulate osteoclastic bone resorption. There was no evidence of morphologic differentiation of the monocytes into osteoclasts during bone resorption."}
{"id": "PMID:16344", "title": "Prelytic damage of red cells in filtrates from peroxidizing microsomes.", "content": "When liver microsomes are incubated in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), their constituent lipids undergo peroxidative degeneration. If erythrocytes are present in such a peroxidizing system, they hemolyze. Filtrates obtained by ultrafiltration of peroxidizing microsomal systems were found to have the capacity to produce prelytic damage in red cells. Filtrates obtained from microsomes that had not undergone peroxidative lipid decomposition were inert. The toxic activity in the active filtrates was not due to continuing oxidation of NADPH nor to continuing liver microsomal lipid peroxidation. Neither the chemical identity of the toxic product or products in active filtrates nor the mechanisms involved in the erythrocyte damage are known at this time.", "contents": "Prelytic damage of red cells in filtrates from peroxidizing microsomes. When liver microsomes are incubated in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH), their constituent lipids undergo peroxidative degeneration. If erythrocytes are present in such a peroxidizing system, they hemolyze. Filtrates obtained by ultrafiltration of peroxidizing microsomal systems were found to have the capacity to produce prelytic damage in red cells. Filtrates obtained from microsomes that had not undergone peroxidative lipid decomposition were inert. The toxic activity in the active filtrates was not due to continuing oxidation of NADPH nor to continuing liver microsomal lipid peroxidation. Neither the chemical identity of the toxic product or products in active filtrates nor the mechanisms involved in the erythrocyte damage are known at this time."}
{"id": "PMID:16348", "title": "Acute erosive gastritis induced by aspirin, ketoprofen, ibuprofen, and naproxen: its prevention by metiamide and cimetidine.", "content": "Aspirin, ketoprofen, ibuprofen, and naproxen all produced acute gastric erosions in rats. Aspirin produced significantly more erosions than ketoprofen, ibuprofen, or naproxen. There was no significant difference between the effects of ketoprofen, ibuprofen, and naproxen. Aspirin and naproxen produced a synergistic effect at higher dosage. Metiamide and cimetidine were effective in preventing this type of experimental acute erosive gastritis.", "contents": "Acute erosive gastritis induced by aspirin, ketoprofen, ibuprofen, and naproxen: its prevention by metiamide and cimetidine. Aspirin, ketoprofen, ibuprofen, and naproxen all produced acute gastric erosions in rats. Aspirin produced significantly more erosions than ketoprofen, ibuprofen, or naproxen. There was no significant difference between the effects of ketoprofen, ibuprofen, and naproxen. Aspirin and naproxen produced a synergistic effect at higher dosage. Metiamide and cimetidine were effective in preventing this type of experimental acute erosive gastritis."}
{"id": "PMID:16349", "title": "Human intestinal helminthiases in East Timor.", "content": "In a study of 210 people from all age groups in the Venilale District of East Timor, 49% had Ascaris lumbricoides, 1% Trichuris trichiura and 67% hookworm infection. There were high Ascaris infection rates among some of the children, but the Trichuris and hookworm rates were almost uniformly low. The factors responsible for these rates are enumerated, and the complex interaction of the factors is discussed. The relative lack of shade and the well-drained limestone soil are probably in large measure responsible for the generally low helminth prevalence. Ascaris was the principal cause of eosinophilia. It was not possible to relate any other haematological or serological findings to the helminths. Apart from the high Ascaris infections in young children, it is not thought that these helminths constitute a heatlh problem.", "contents": "Human intestinal helminthiases in East Timor. In a study of 210 people from all age groups in the Venilale District of East Timor, 49% had Ascaris lumbricoides, 1% Trichuris trichiura and 67% hookworm infection. There were high Ascaris infection rates among some of the children, but the Trichuris and hookworm rates were almost uniformly low. The factors responsible for these rates are enumerated, and the complex interaction of the factors is discussed. The relative lack of shade and the well-drained limestone soil are probably in large measure responsible for the generally low helminth prevalence. Ascaris was the principal cause of eosinophilia. It was not possible to relate any other haematological or serological findings to the helminths. Apart from the high Ascaris infections in young children, it is not thought that these helminths constitute a heatlh problem."}
{"id": "PMID:16352", "title": "The influence of coronary arterial pH on myocardial oxygen demand.", "content": "The purpose of this study was to examine the magnitude of the influence of coronary arterial pH (pHa) on myocardial oxygen uptake (MV 02). In order to isolate and control the recognized determinants of MV02, a perfused heart preparation was developed which permitted control of heart rate and pressure and flow work. A perfusion system was used which allowed independent regulation of O2 N2 and CO2 flow to a membrane lung and precise control of coronary blood flow. Myocardial oxygen delivery (Ca02 x flow) could be held constant (+/- 1%) during 4 hours of perfusion. Catheter decompression of both ventricles prevented any external pressure or flow work. Blood temperature was maintained at 37.27 +/- 0.07degrees C. Perfusing blood pH was related initially to spontaneous heart rate in five dogs: pulse = 82 pH - 487. In 12 subsequent animals heart rate was fixed. MV02 was directly and significantly related to coronary arterial pH in all animals studied: MVO2% = 109 pH - 143 (r = 0.823). An increase in pHa of 0.1 will increase MV02 by 10.9%. This study isolates pH as a determinant of myocardial oxygen uptake and indicates that progressive alkalosis induces increased myocardial oxygen uptake. This must be recognized in the treatment of patients with compromised myocardial function and rerional areas of ischemia.", "contents": "The influence of coronary arterial pH on myocardial oxygen demand. The purpose of this study was to examine the magnitude of the influence of coronary arterial pH (pHa) on myocardial oxygen uptake (MV 02). In order to isolate and control the recognized determinants of MV02, a perfused heart preparation was developed which permitted control of heart rate and pressure and flow work. A perfusion system was used which allowed independent regulation of O2 N2 and CO2 flow to a membrane lung and precise control of coronary blood flow. Myocardial oxygen delivery (Ca02 x flow) could be held constant (+/- 1%) during 4 hours of perfusion. Catheter decompression of both ventricles prevented any external pressure or flow work. Blood temperature was maintained at 37.27 +/- 0.07degrees C. Perfusing blood pH was related initially to spontaneous heart rate in five dogs: pulse = 82 pH - 487. In 12 subsequent animals heart rate was fixed. MV02 was directly and significantly related to coronary arterial pH in all animals studied: MVO2% = 109 pH - 143 (r = 0.823). An increase in pHa of 0.1 will increase MV02 by 10.9%. This study isolates pH as a determinant of myocardial oxygen uptake and indicates that progressive alkalosis induces increased myocardial oxygen uptake. This must be recognized in the treatment of patients with compromised myocardial function and rerional areas of ischemia."}
{"id": "PMID:16368", "title": "Distribution of acid phosphatase activity in the larval stages of Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis in the mosquito.", "content": "The histochemical distribution of acid phosphatase in microfilariae and in the larval stages of four mosquito-borne filariae: Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis was studied using naphthol AS-TR-hexazonium technique and light microscopy. Accurate differentiation between microfilariae of the four species could be made on the basis of their patterns of acid phosphatase activity. In contrast to microfilariae in the blood, the larval stages in the mosquito exhibited different patterns of acid phosphatase activity which were characteristic for each developmental stage. In the first-stage larva, maximum acid phosphatase activity was found in the anal vesicle, the growing anal membrane (anal plug), buccal cavity, forming intestine and rectum. In the second-stage larva, acid phosphatase activity was present throughout the alimentary canal, particularly in the section of the intestine and rectum. In the infective third-stage larva, the whole body stained densely red. The reaction for acid phosphatase in the excretory cell complex of W. bancrofti and of both species of Brugia gradually decreased in intensity and disappeared completely towards the end of the first-larval stage, whereas in D. immitis a strong reaction in this area persisted throughout the larval life in the mosquito. The presence or absence of enzymic activity in the excretory cell complex and in the Mundgebilde (amphids) of the developing larvae can be used as an adjunctive diagnostic method.", "contents": "Distribution of acid phosphatase activity in the larval stages of Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis in the mosquito. The histochemical distribution of acid phosphatase in microfilariae and in the larval stages of four mosquito-borne filariae: Wuchereria bancrofti, Brugia malayi, B. pahangi and Dirofilaria immitis was studied using naphthol AS-TR-hexazonium technique and light microscopy. Accurate differentiation between microfilariae of the four species could be made on the basis of their patterns of acid phosphatase activity. In contrast to microfilariae in the blood, the larval stages in the mosquito exhibited different patterns of acid phosphatase activity which were characteristic for each developmental stage. In the first-stage larva, maximum acid phosphatase activity was found in the anal vesicle, the growing anal membrane (anal plug), buccal cavity, forming intestine and rectum. In the second-stage larva, acid phosphatase activity was present throughout the alimentary canal, particularly in the section of the intestine and rectum. In the infective third-stage larva, the whole body stained densely red. The reaction for acid phosphatase in the excretory cell complex of W. bancrofti and of both species of Brugia gradually decreased in intensity and disappeared completely towards the end of the first-larval stage, whereas in D. immitis a strong reaction in this area persisted throughout the larval life in the mosquito. The presence or absence of enzymic activity in the excretory cell complex and in the Mundgebilde (amphids) of the developing larvae can be used as an adjunctive diagnostic method."}
{"id": "PMID:16363", "title": "Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels.", "content": "The mechanism by which the local effect of CO2ON pial arterioles is exerted was examined in anesthetized cats equipped with a cranial window for the direct observation of the microcirculation of the parietal cortex. The dilation of pial arterioles in response to application of artificial cerebrospinal fluid with low pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly increased. The constriction of pial arterioles in response to application of artificial cerebrospinal fluid with high pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly decreased. Finally, pial arterioles did not change their caliber in response to application of cerebrospinal fluid with unchanged pH but markedly increased or decreased Pco, or bicarbonate ion concentration. These results show that the action of CO2 on cerebral vessels is exerted via changes in extracellular fluid pH and that molecular CO2 and bicarbonate ions do not have independent vasoactivity on these vessels.", "contents": "Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels. The mechanism by which the local effect of CO2ON pial arterioles is exerted was examined in anesthetized cats equipped with a cranial window for the direct observation of the microcirculation of the parietal cortex. The dilation of pial arterioles in response to application of artificial cerebrospinal fluid with low pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly increased. The constriction of pial arterioles in response to application of artificial cerebrospinal fluid with high pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly decreased. Finally, pial arterioles did not change their caliber in response to application of cerebrospinal fluid with unchanged pH but markedly increased or decreased Pco, or bicarbonate ion concentration. These results show that the action of CO2 on cerebral vessels is exerted via changes in extracellular fluid pH and that molecular CO2 and bicarbonate ions do not have independent vasoactivity on these vessels."}
{"id": "PMID:16364", "title": "Effect of carotid artery ligation on regional cerebral blood flow in normotensive and spontaneously hypertensive rats.", "content": "Regional cerebral blood flow (rCBF) was measured in normotensive rate (NTR) and spontaneously hypertensive rats (SHR), in a lightly anesthetized state and with control of PaCO2 by artificial ventilation. Without carotid artery ligation, NTR and SHR showed almost identical rCBF values and distribution, despite significantly elevated levels of blood pressure in SHR. Bilateral carotid artery ligation, however, caused much more pronounced decreases of rCBF (ischemia) in SHR than NTR, in regions supplied by the carotid artery. The reduction of rCBF in SHR was rather homogenous and symmetrical. Mechanisms causing the differences between NTR and SHR are discussed.", "contents": "Effect of carotid artery ligation on regional cerebral blood flow in normotensive and spontaneously hypertensive rats. Regional cerebral blood flow (rCBF) was measured in normotensive rate (NTR) and spontaneously hypertensive rats (SHR), in a lightly anesthetized state and with control of PaCO2 by artificial ventilation. Without carotid artery ligation, NTR and SHR showed almost identical rCBF values and distribution, despite significantly elevated levels of blood pressure in SHR. Bilateral carotid artery ligation, however, caused much more pronounced decreases of rCBF (ischemia) in SHR than NTR, in regions supplied by the carotid artery. The reduction of rCBF in SHR was rather homogenous and symmetrical. Mechanisms causing the differences between NTR and SHR are discussed."}
{"id": "PMID:16372", "title": "Aggregation of calcium oxalate crystals: effect of urine and various inhibitors.", "content": "The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons.", "contents": "Aggregation of calcium oxalate crystals: effect of urine and various inhibitors. The influence of various factors on aggregation of calcium oxalate crystals in vitro was determined. Aggregation was assessed by filtering the crystal suspension and measuring the flow rate through a filter. 10% urine completely inhibited aggregation. Orthophosphate and magnesium at concentrations occuring in urine had no effect. Citrate had no effect at 10(-4) M ,but did inhibit at 10(-3) M. The latter effect is probably due to calcium binding. Pyrophosphate and disodium dichioromethylene diphosphonate (C12MDP) inhibited strongly at 10(-4) M, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at 10(-5) M, whereas pentanemonophosphonate had no effect. Uromucoid also did not show any inhibitory activity. Studies by means of heat inactivation, ultrafiltration and fractionation on DEAE-cellulose and gel-filtration indicated that the inhibitory activity was heterogenous and that the major part was larger than 10 000 daltons."}
{"id": "PMID:16375", "title": "[Use of preparations with sympatholytic activity for prevention and treatment of postoperative intestinal paresis].", "content": "For prophylaxis and treatment of postoperative intestinal paresis the authors employed in 1059 patients gangliolytics and drugs of sympatholytic action -- benzohexonium, aminazine, pyrroxane. An early sympathetic blockade after abdominal surgery was found to be effective both with respect to the prophylaxis of intestinal paresis and in treatment of grave functional disturbances of enteric motility, that develop in different abdominal complications.", "contents": "[Use of preparations with sympatholytic activity for prevention and treatment of postoperative intestinal paresis]. For prophylaxis and treatment of postoperative intestinal paresis the authors employed in 1059 patients gangliolytics and drugs of sympatholytic action -- benzohexonium, aminazine, pyrroxane. An early sympathetic blockade after abdominal surgery was found to be effective both with respect to the prophylaxis of intestinal paresis and in treatment of grave functional disturbances of enteric motility, that develop in different abdominal complications."}
{"id": "PMID:16377", "title": "[Determination of the effective concentration of Jodonal a for the disinfection of the skin and teats after milking].", "content": "The bactericidal effectivity of Jodonal A in 1:10, 1:5, and 1:3 solutions was tested on human skin and on the teats of cow mammary glands. The 1:3 dilution ratio proved best for three-minute exposure. Jodonal A used in this concentration in 522 cows for the post-milking disinfection of teats for 10 months exerted no harmful effect on the skin of the mammary glands.", "contents": "[Determination of the effective concentration of Jodonal a for the disinfection of the skin and teats after milking]. The bactericidal effectivity of Jodonal A in 1:10, 1:5, and 1:3 solutions was tested on human skin and on the teats of cow mammary glands. The 1:3 dilution ratio proved best for three-minute exposure. Jodonal A used in this concentration in 522 cows for the post-milking disinfection of teats for 10 months exerted no harmful effect on the skin of the mammary glands."}
{"id": "PMID:16378", "title": "[Devitalizing effect of Jodonal A in vitro on bacteria subject to a short-term exposure].", "content": "In a three-minute exposure in vitro Jodonal A devitalized a culture of serological group B streptococci in a 2% concentration, Staphylococcus aureus in a 16% concentration, Pneumococcus in a 4.5% concentration, Corynebacterium pyogenes in a 2.5% concentration, Pseudomonas aeruginosa in a 3% concentration, and Klebsiella pneumoniae in a 2% concentration. Hence Jodonal A concentrations higher than 16% should be tested for udder teat disinfection after the removal of teat cups.", "contents": "[Devitalizing effect of Jodonal A in vitro on bacteria subject to a short-term exposure]. In a three-minute exposure in vitro Jodonal A devitalized a culture of serological group B streptococci in a 2% concentration, Staphylococcus aureus in a 16% concentration, Pneumococcus in a 4.5% concentration, Corynebacterium pyogenes in a 2.5% concentration, Pseudomonas aeruginosa in a 3% concentration, and Klebsiella pneumoniae in a 2% concentration. Hence Jodonal A concentrations higher than 16% should be tested for udder teat disinfection after the removal of teat cups."}
{"id": "PMID:16385", "title": "[Acid gamma-amylase of rabbit and human brain].", "content": "Preparations of acidic gamma-amylase, which cleaved glycogen and maltose, were isolated from human and rabbit brain tissues. The specific activity of the gamma-amylase preparations from human brain was approximately twice higher than the activity of the enzyme from rabbit brain. In degradation of glycogen gamma-amylases from human and rabbit brain had the pH optima at pH 4.9 and 4.6 and with maltose as a substrate- at pH 4.3 and 4.1, respectively. gamma-Amylases from both sources possessed the high stability in presence of monovalent cations. K+ distinctly increased the cleavage of glycogen by gamma-amylase from human and rabbit brain. alpha, alpha-Trehalose and alpha-menthyl glucoside proved to be inhibitors of the glucoamylase activity of the enzymes from both sources. Km values of the gamma-amylases for glycogen were equal to 19.3 mM 19.8 and for maltose -5.54 mM and 5.78 mM, respectively. The data obtained suggest that acidic gamma-amylases from human and rabbit brain are similar to acidic gamma-amylases from other sources.", "contents": "[Acid gamma-amylase of rabbit and human brain]. Preparations of acidic gamma-amylase, which cleaved glycogen and maltose, were isolated from human and rabbit brain tissues. The specific activity of the gamma-amylase preparations from human brain was approximately twice higher than the activity of the enzyme from rabbit brain. In degradation of glycogen gamma-amylases from human and rabbit brain had the pH optima at pH 4.9 and 4.6 and with maltose as a substrate- at pH 4.3 and 4.1, respectively. gamma-Amylases from both sources possessed the high stability in presence of monovalent cations. K+ distinctly increased the cleavage of glycogen by gamma-amylase from human and rabbit brain. alpha, alpha-Trehalose and alpha-menthyl glucoside proved to be inhibitors of the glucoamylase activity of the enzymes from both sources. Km values of the gamma-amylases for glycogen were equal to 19.3 mM 19.8 and for maltose -5.54 mM and 5.78 mM, respectively. The data obtained suggest that acidic gamma-amylases from human and rabbit brain are similar to acidic gamma-amylases from other sources."}
{"id": "PMID:16388", "title": "[Intracellular localization of the processes of biosynthesis and degradation of NADP in skeletal muscle].", "content": "In studies on intracellular NADP localization the process of NADP biosynthesis was observed in mitochondria and hyaloplasm of rabbit sceletal muscle cells. This synthesis was not found in microsomal and nuclear fractions. The seasonal alterations in the NAD-kinase activity were established: in autumn and winter months NADP synthesis proceeded at the maximal rate in hyaloplasm; in sping months the higher specific activity was observed in mitochondrial fraction. The rate of NADP synthesis was 2-5 times lower in initial and reconstructed (hyaloplasm+cell organelles) homogenate then in hyaloplasm, among the enzymes, degrading the NADP molecule in sceletal muscle, the highest activity was exhibitel by nucleosidase, which was localized mainly in mitochondria and microsomes. Mechanisms for regulation of the rate of NADP synthesis and degradation in cytostructures of rabbit sceletal muscles are discussed.", "contents": "[Intracellular localization of the processes of biosynthesis and degradation of NADP in skeletal muscle]. In studies on intracellular NADP localization the process of NADP biosynthesis was observed in mitochondria and hyaloplasm of rabbit sceletal muscle cells. This synthesis was not found in microsomal and nuclear fractions. The seasonal alterations in the NAD-kinase activity were established: in autumn and winter months NADP synthesis proceeded at the maximal rate in hyaloplasm; in sping months the higher specific activity was observed in mitochondrial fraction. The rate of NADP synthesis was 2-5 times lower in initial and reconstructed (hyaloplasm+cell organelles) homogenate then in hyaloplasm, among the enzymes, degrading the NADP molecule in sceletal muscle, the highest activity was exhibitel by nucleosidase, which was localized mainly in mitochondria and microsomes. Mechanisms for regulation of the rate of NADP synthesis and degradation in cytostructures of rabbit sceletal muscles are discussed."}
{"id": "PMID:16389", "title": "[Isolation of the islands of Langerhans from rat pancreas and determination of proteolytic activity in them].", "content": "A modified method for isolation of Langerhans islands from rat pancreas is described. The islands obtained were free from acinous tissue as shown by means of an amylase test and by microscopy. In homogenates of the islands proteolytic activities were observed (pH optimum at 5.3--5.5 and 6.9--7.2).", "contents": "[Isolation of the islands of Langerhans from rat pancreas and determination of proteolytic activity in them]. A modified method for isolation of Langerhans islands from rat pancreas is described. The islands obtained were free from acinous tissue as shown by means of an amylase test and by microscopy. In homogenates of the islands proteolytic activities were observed (pH optimum at 5.3--5.5 and 6.9--7.2)."}
{"id": "PMID:16390", "title": "[Pyridine nucleotide content in the brain and myocardium of rats under combined effect of hypercapnia, hypoxia and cooling].", "content": "In experiments with rats, subjected to single and repeated simultaneous effect of hypercapnia, hypoxia and cooling, contents of pyridine nucleotides (NAD, NADP, NAD-H2 and NADP-H2) and macroergic substances were studied and also the activity of dehydrogenases of the pentose pathway was determined in brain and myocardium. In brain NADP was not practically determined and in heart its content was increased after the first and the second treatments. Content of NADP-H2 was distinctly decreased in both tissues after the single treatment. NAD was not altered in the tissues in all the periods studied. The amount of NAD-H2 was decreased in brain after the single treatment and it was increased in myocardium after the repeated one. In the activity of dehydrogenases marked alterations were not observed. Total macroergic substances were not altered in brain after the single treatment and after the repeated one they were increased mainly due to the ATP increase. In myocardium total macroergic substances were decreased after the both treatments.", "contents": "[Pyridine nucleotide content in the brain and myocardium of rats under combined effect of hypercapnia, hypoxia and cooling]. In experiments with rats, subjected to single and repeated simultaneous effect of hypercapnia, hypoxia and cooling, contents of pyridine nucleotides (NAD, NADP, NAD-H2 and NADP-H2) and macroergic substances were studied and also the activity of dehydrogenases of the pentose pathway was determined in brain and myocardium. In brain NADP was not practically determined and in heart its content was increased after the first and the second treatments. Content of NADP-H2 was distinctly decreased in both tissues after the single treatment. NAD was not altered in the tissues in all the periods studied. The amount of NAD-H2 was decreased in brain after the single treatment and it was increased in myocardium after the repeated one. In the activity of dehydrogenases marked alterations were not observed. Total macroergic substances were not altered in brain after the single treatment and after the repeated one they were increased mainly due to the ATP increase. In myocardium total macroergic substances were decreased after the both treatments."}
{"id": "PMID:16391", "title": "[Adenyl cyclase and adenosine-3',5'-monophosphate phosphodiesteraze: their nature, properties and regulation].", "content": "Modern data on the nature, properties and pathways of regulation enzymes, participated metabolism of cyclic, adenosine-3',5'-monophosphate, are described. Much consideration is being given to the problem of regulation of the phosphodiesterase activity due to the effect of Ca2+-binding proteins.", "contents": "[Adenyl cyclase and adenosine-3',5'-monophosphate phosphodiesteraze: their nature, properties and regulation]. Modern data on the nature, properties and pathways of regulation enzymes, participated metabolism of cyclic, adenosine-3',5'-monophosphate, are described. Much consideration is being given to the problem of regulation of the phosphodiesterase activity due to the effect of Ca2+-binding proteins."}
{"id": "PMID:16392", "title": "[Chemiluminescence of the blood serum in the presence of divalent iron salts].", "content": "On incubation of diluted blood serum with ferrous ions kinetics of chemiluminescence, typical for lipid containing systems, was observed. It comprised several sequental steps: quick flash, inhibition of the chemiluminescence, slow flash with subsequent steady-state luminescence. At each step of the phenomenon a correlation was found between the intensity of chemiluminescence, the rate of accumulation of products of lipid peroxidation (malone dialdehyde) and concentration of Fe2+ in the mixture. The data obtained suggest that chemiluminescence of blood serum in presence of Fe2+ is due to lipid peroxidation in the serum. Kinetics of the reaction and shape of the chemiluminiscence curve depended upon a number of factors: dilution of blood serum, concentration of Fe2+ added, temperature, pH and (if blood plasma was used) type of an anticoagulant use. Only in blood lipoproteins, mainly in beta-lipoproteins, the distinctive pattern of peroxidation was developed with simultaneous accumulation of malone dialdehyde, oxidation of ferrous ions and ultralow chemiluminescence. In protein fraction of blood serum addition of Fe2+ caused only the quick splash of chemiluminescence without the malone dialdehyde production.", "contents": "[Chemiluminescence of the blood serum in the presence of divalent iron salts]. On incubation of diluted blood serum with ferrous ions kinetics of chemiluminescence, typical for lipid containing systems, was observed. It comprised several sequental steps: quick flash, inhibition of the chemiluminescence, slow flash with subsequent steady-state luminescence. At each step of the phenomenon a correlation was found between the intensity of chemiluminescence, the rate of accumulation of products of lipid peroxidation (malone dialdehyde) and concentration of Fe2+ in the mixture. The data obtained suggest that chemiluminescence of blood serum in presence of Fe2+ is due to lipid peroxidation in the serum. Kinetics of the reaction and shape of the chemiluminiscence curve depended upon a number of factors: dilution of blood serum, concentration of Fe2+ added, temperature, pH and (if blood plasma was used) type of an anticoagulant use. Only in blood lipoproteins, mainly in beta-lipoproteins, the distinctive pattern of peroxidation was developed with simultaneous accumulation of malone dialdehyde, oxidation of ferrous ions and ultralow chemiluminescence. In protein fraction of blood serum addition of Fe2+ caused only the quick splash of chemiluminescence without the malone dialdehyde production."}
{"id": "PMID:16393", "title": "[Androgen participation in realizing the action of hydrocortisone and insulin on tyrosine-alpha-ketoglutarate transaminase synthesis in rat liver mitochondria].", "content": "Castration of adult rats did not distinctly alter the tyrosine alpha-ketoglutarate transaminase activity in liver tissue mitochondria. Administration of hydrocortisone caused the more pronounced increased of the tyrosine alpha-ketoglutarate transaminae activity in liver tissue mitochondria of young males as compared with the adult intact rats. Castration of adult rats did no alter stimulating effect of the glucocorticoid. Insulin decreased the stimulating effect of hydrocortisone on the synthesis of the synthesis of the enzyme in liver tissue mitochondria of young and adult castrated males. Insulin decreased the effect of hydrocortisone in adult castrated rats, provided with excess of testosterone propionate and did not change the effect in adul intact animals.", "contents": "[Androgen participation in realizing the action of hydrocortisone and insulin on tyrosine-alpha-ketoglutarate transaminase synthesis in rat liver mitochondria]. Castration of adult rats did not distinctly alter the tyrosine alpha-ketoglutarate transaminase activity in liver tissue mitochondria. Administration of hydrocortisone caused the more pronounced increased of the tyrosine alpha-ketoglutarate transaminae activity in liver tissue mitochondria of young males as compared with the adult intact rats. Castration of adult rats did no alter stimulating effect of the glucocorticoid. Insulin decreased the stimulating effect of hydrocortisone on the synthesis of the synthesis of the enzyme in liver tissue mitochondria of young and adult castrated males. Insulin decreased the effect of hydrocortisone in adult castrated rats, provided with excess of testosterone propionate and did not change the effect in adul intact animals."}
{"id": "PMID:16394", "title": "[Purification and properties of the serotonin-stimulated adenylate deaminase from the mitochondrial fraction of rat liver].", "content": "A method is described for partial purification of structurally bound adenilate desaminase from rat liver tissue mitochondria; the enzyme was stimulated by parenteral administration of serotonine. The enzymatic preparations obtained desaminated AMP, 2',3'-AMP and adenosine, but they did not effect on ATP, 2',3'-cycloAMP or 3',5'-cycloAMP. The maximal rate of desaminating of these substances by AMP-desaminase, stimulated with serotonine, exceeded approximately 1.4-fold the same values, which were obtained for the enzymatic preparations from liver tissue mitochondria of rats, administered with physiological solution. Mitochondrial serotomine-stimulated adenilate desaminase was differentiated from the other soluble adenilate desaminases by some properties; the enzyme was likely to participate also in the regulation of nucleotides balance in the organism.", "contents": "[Purification and properties of the serotonin-stimulated adenylate deaminase from the mitochondrial fraction of rat liver]. A method is described for partial purification of structurally bound adenilate desaminase from rat liver tissue mitochondria; the enzyme was stimulated by parenteral administration of serotonine. The enzymatic preparations obtained desaminated AMP, 2',3'-AMP and adenosine, but they did not effect on ATP, 2',3'-cycloAMP or 3',5'-cycloAMP. The maximal rate of desaminating of these substances by AMP-desaminase, stimulated with serotonine, exceeded approximately 1.4-fold the same values, which were obtained for the enzymatic preparations from liver tissue mitochondria of rats, administered with physiological solution. Mitochondrial serotomine-stimulated adenilate desaminase was differentiated from the other soluble adenilate desaminases by some properties; the enzyme was likely to participate also in the regulation of nucleotides balance in the organism."}
{"id": "PMID:16395", "title": "[Methylmalonic acid excretion in experimental B2-avitaminosis in rats].", "content": "Providing of rats with a diet, deficient in vitamin B2 within 2 and 5 weeks, was not shown to be accompanied by an increase in excretion of methylmalonic acid. In the animals some tendency to the increased excretion of methylmalonic acid was observed within 8 weeks of the diet. The data obtained suggest that the test for excretion of methylmalonic acid was the highly specific as a pattern of supply with vitamin B12. The possible role of vitamin B2 and flavoproteins in biosynthesis of coenzyme forms of vitamin B12 is discussed.", "contents": "[Methylmalonic acid excretion in experimental B2-avitaminosis in rats]. Providing of rats with a diet, deficient in vitamin B2 within 2 and 5 weeks, was not shown to be accompanied by an increase in excretion of methylmalonic acid. In the animals some tendency to the increased excretion of methylmalonic acid was observed within 8 weeks of the diet. The data obtained suggest that the test for excretion of methylmalonic acid was the highly specific as a pattern of supply with vitamin B12. The possible role of vitamin B2 and flavoproteins in biosynthesis of coenzyme forms of vitamin B12 is discussed."}
{"id": "PMID:16397", "title": "[Isoelectric focusing in a boroborate buffer-mannitol system (BBM)].", "content": "The data of the following study of isoelectric focusing in the system 'buffer--nonelectrolyte' are described. The method was shown to be employed for study of proteins, when human serum albumin was used as a model. A standard method and an apparatus device are proposed for the analytical isoelectric focusing of proteins both in the wide (pH 4.00-8.50) and in the limit (PH 4.50-6.00) PH regions. Advantages and limitations of the method are discussed as compared with the method of isoelectric focusing in ampholines.", "contents": "[Isoelectric focusing in a boroborate buffer-mannitol system (BBM)]. The data of the following study of isoelectric focusing in the system 'buffer--nonelectrolyte' are described. The method was shown to be employed for study of proteins, when human serum albumin was used as a model. A standard method and an apparatus device are proposed for the analytical isoelectric focusing of proteins both in the wide (pH 4.00-8.50) and in the limit (PH 4.50-6.00) PH regions. Advantages and limitations of the method are discussed as compared with the method of isoelectric focusing in ampholines."}
{"id": "PMID:16402", "title": "[Acid-base and water-electrolyte status in animals with experimental tumors].", "content": "It is noted that rats with Heren carcinoma show alkalization of blood, decreased pH levels of the urine, hypokalemia, hypocalcemia, hypomagnesiemia, sodium and water retention, increased kalium level in the liver. Analogous changes are observed in rabbits with Brown-Pearce carcinoma. The organism of tumor-bearing rats responds to stress effects otherwise than the organism of normal animals.", "contents": "[Acid-base and water-electrolyte status in animals with experimental tumors]. It is noted that rats with Heren carcinoma show alkalization of blood, decreased pH levels of the urine, hypokalemia, hypocalcemia, hypomagnesiemia, sodium and water retention, increased kalium level in the liver. Analogous changes are observed in rabbits with Brown-Pearce carcinoma. The organism of tumor-bearing rats responds to stress effects otherwise than the organism of normal animals."}
{"id": "PMID:16398", "title": "[Kinetic properties of partially purified glucosephosphate dehydrogenase of human erythrocytes].", "content": "Partially purified glucose-6-phosphate dehydrogenase was isolated from small amounts of human erythrocytes (15-20 ml). The Km value for glucose-6-phosphate was 35.0 +/- 3.0 micronM, the Km for NADP was 4.27 +/- 0.3 micronM. The optimal activity of the enzyme was at pH 9.0. Glucose-6-phosphate dehydrogenase, dialyzed in presence of 1-10(-5) M NADP, had critical temperature about 52 degrees within 10 min of incubation; without NADP it was at 45 degrees. The method for isolation and purification of the enzyme was modified.", "contents": "[Kinetic properties of partially purified glucosephosphate dehydrogenase of human erythrocytes]. Partially purified glucose-6-phosphate dehydrogenase was isolated from small amounts of human erythrocytes (15-20 ml). The Km value for glucose-6-phosphate was 35.0 +/- 3.0 micronM, the Km for NADP was 4.27 +/- 0.3 micronM. The optimal activity of the enzyme was at pH 9.0. Glucose-6-phosphate dehydrogenase, dialyzed in presence of 1-10(-5) M NADP, had critical temperature about 52 degrees within 10 min of incubation; without NADP it was at 45 degrees. The method for isolation and purification of the enzyme was modified."}
{"id": "PMID:16396", "title": "[Method for the direct spectrophotometric determination of the rate of the tyrosine hydroxylase reaction].", "content": "A rate of the tyrosine hydroxylase reaction was estimated by an increase in absorption at 335 nm, which was caused by oxidation of pterin cofactor 6,7-dimethyl-5, 6, 7, 8-tetrahydroxypterin (DMPH) coupled with the convertion of the substrate 1-tyrosine into dihydroxyphenylalanine. At pH 6.2 the ratios of molar extinction were as follows: in trisacetate ADMPH4-1370, ADMPH2-5350; in tris-malate tadmph4-1250, admph25300. the enzyme, associated with membranes, had the Km value for Tyr-0.045 mM, the Km for DMPH4 was 0.18 mM; the soluble enzyme had Km for Tyr-0,050 mM, the Km for DMPH4 was 0.74 mM. The stoichiometry of the reaction was 1:1 (I mole DOPA per I mole of DMPH2 formed).", "contents": "[Method for the direct spectrophotometric determination of the rate of the tyrosine hydroxylase reaction]. A rate of the tyrosine hydroxylase reaction was estimated by an increase in absorption at 335 nm, which was caused by oxidation of pterin cofactor 6,7-dimethyl-5, 6, 7, 8-tetrahydroxypterin (DMPH) coupled with the convertion of the substrate 1-tyrosine into dihydroxyphenylalanine. At pH 6.2 the ratios of molar extinction were as follows: in trisacetate ADMPH4-1370, ADMPH2-5350; in tris-malate tadmph4-1250, admph25300. the enzyme, associated with membranes, had the Km value for Tyr-0.045 mM, the Km for DMPH4 was 0.18 mM; the soluble enzyme had Km for Tyr-0,050 mM, the Km for DMPH4 was 0.74 mM. The stoichiometry of the reaction was 1:1 (I mole DOPA per I mole of DMPH2 formed)."}
{"id": "PMID:16405", "title": "[Neurohumoral influences of steroid hormones on sexual responsiveness in women (author's transl)].", "content": "An analysis has been carried out on the basis of endocrinological and psychosomatic studies of the influence of steroid hormones, acting via probable transmitter substances, on the sexual response in women. From a review in the literature it can be concluded that among other factors the endocrine state of the women determines her sexual response and behaviour. However, the present lack of specific psychological tests is pointed out, as well as the absence of relevant hormonal data to the sexual sphere, both normal and pathological.", "contents": "[Neurohumoral influences of steroid hormones on sexual responsiveness in women (author's transl)]. An analysis has been carried out on the basis of endocrinological and psychosomatic studies of the influence of steroid hormones, acting via probable transmitter substances, on the sexual response in women. From a review in the literature it can be concluded that among other factors the endocrine state of the women determines her sexual response and behaviour. However, the present lack of specific psychological tests is pointed out, as well as the absence of relevant hormonal data to the sexual sphere, both normal and pathological."}
{"id": "PMID:16406", "title": "[The influence of socio-economic factors on the results of a prematury-Dysmaturity prevention programme (author's transl)].", "content": "All high-risk gravidae with regard to prematurity and dysmaturity (PDP programme) were collected over a time-limited period. More than two thirds (n = 72) of these women were submitted to intensive care (PDP group); one third (n = 33) (control group) refused intensive care. Furthermore, socio-economic factors were taken into consideration in this study and appropriate classification into 4 groups was undertaken. Gravidae of a higher social class were more often willing to undergo intensive care than gravidae of a lower class. In the PDP group 75% of the gravidae were delivered after the end of the 36th gestational week and 51% of the gravidae in the control group. A similar relationship was found in regard to the birth weight of the newborn infants: in the PDP group 74.4% of the babies weighed over 2500 g at birth in contrast to the respective figure of 42.9% in the control group. However, this socio-economic study shows that the results of intensive care are much more successful in women from a lower social stata than in women from a higher social class.", "contents": "[The influence of socio-economic factors on the results of a prematury-Dysmaturity prevention programme (author's transl)]. All high-risk gravidae with regard to prematurity and dysmaturity (PDP programme) were collected over a time-limited period. More than two thirds (n = 72) of these women were submitted to intensive care (PDP group); one third (n = 33) (control group) refused intensive care. Furthermore, socio-economic factors were taken into consideration in this study and appropriate classification into 4 groups was undertaken. Gravidae of a higher social class were more often willing to undergo intensive care than gravidae of a lower class. In the PDP group 75% of the gravidae were delivered after the end of the 36th gestational week and 51% of the gravidae in the control group. A similar relationship was found in regard to the birth weight of the newborn infants: in the PDP group 74.4% of the babies weighed over 2500 g at birth in contrast to the respective figure of 42.9% in the control group. However, this socio-economic study shows that the results of intensive care are much more successful in women from a lower social stata than in women from a higher social class."}
{"id": "PMID:16399", "title": "[Role of lipid peroxides in the pathogenesis of arteriosclerosis. Detoxication of lipid peroxides by the glutathione-peroxidase system in the aorta].", "content": "In aorta of intact rabbits the high activity of glutathione-peroxidase, which detoxicates lipoperoxides, was observed. In aorta of animals with pronounced experimental atheromatosis the enzyme activity did not distinctly differ from the control values. The animals with high initial content of glutathione-peroxidase in aorta were shown to be less subjected to the impairment in alimentary atherosclerosis.", "contents": "[Role of lipid peroxides in the pathogenesis of arteriosclerosis. Detoxication of lipid peroxides by the glutathione-peroxidase system in the aorta]. In aorta of intact rabbits the high activity of glutathione-peroxidase, which detoxicates lipoperoxides, was observed. In aorta of animals with pronounced experimental atheromatosis the enzyme activity did not distinctly differ from the control values. The animals with high initial content of glutathione-peroxidase in aorta were shown to be less subjected to the impairment in alimentary atherosclerosis."}
{"id": "PMID:16407", "title": "[New aspects in diagnosis and therapy of placental insufficiency. Placental perfusion measurements; placental perfusion test (PPT) and betamimetic long term treatment (clinical and experimental data (authors transl)].", "content": "The rate of utero-placental blood flow depends on functional components (perfusion pressure and flow resistance within the area of the vascular bed of the placenta), as well as on morphological factors (regressive changes in the placenta). Different primary maternal conditions and diseases may lower the rate of placental flow, leading to placental insufficiency; the highest percentage, by far, of placental dysfunction is found in patients suffering from gestosis. Hypocirculation initially present in cases of EPH gestosis and caused by arteriolar spasms triggers off a vicious circle involving placental infarction and severe reduction in the utero-placental perfusion rate. This in turn leads to fetal hypotrophy, a high rate of premature births and perinatal mortality. Verification of HPL, HCG, alpha-Fetoprotein or E3 in maternal serum and amniotic fluid or urine greatly improved the recording of partial placental functions. Along with ultrasonic biometry, cardiotocography and amnioscopy, these hormonal parameters allow only indirect assessment of the placental function. On the other hand, measurements of the utero-placental flow offers a direct approach. In order to evaluate the placental flow measurements it is imperative to obtain a curve indicating the course over the last third of the pregnancy-in addition to establishing a general normal range. In case of placental insufficiency, it is necessary to determine whether this is due to functional disorders alone, or to more extenisve morphological changes. A placental perfusion test (PPT) was developed in order to make this distinction. Beta2-mimetic treatment is indicated if functional factors predominate, whereby it appears essential to obtain the requisite experimental data for precise quantification of beta-mimetic action.", "contents": "[New aspects in diagnosis and therapy of placental insufficiency. Placental perfusion measurements; placental perfusion test (PPT) and betamimetic long term treatment (clinical and experimental data (authors transl)]. The rate of utero-placental blood flow depends on functional components (perfusion pressure and flow resistance within the area of the vascular bed of the placenta), as well as on morphological factors (regressive changes in the placenta). Different primary maternal conditions and diseases may lower the rate of placental flow, leading to placental insufficiency; the highest percentage, by far, of placental dysfunction is found in patients suffering from gestosis. Hypocirculation initially present in cases of EPH gestosis and caused by arteriolar spasms triggers off a vicious circle involving placental infarction and severe reduction in the utero-placental perfusion rate. This in turn leads to fetal hypotrophy, a high rate of premature births and perinatal mortality. Verification of HPL, HCG, alpha-Fetoprotein or E3 in maternal serum and amniotic fluid or urine greatly improved the recording of partial placental functions. Along with ultrasonic biometry, cardiotocography and amnioscopy, these hormonal parameters allow only indirect assessment of the placental function. On the other hand, measurements of the utero-placental flow offers a direct approach. In order to evaluate the placental flow measurements it is imperative to obtain a curve indicating the course over the last third of the pregnancy-in addition to establishing a general normal range. In case of placental insufficiency, it is necessary to determine whether this is due to functional disorders alone, or to more extenisve morphological changes. A placental perfusion test (PPT) was developed in order to make this distinction. Beta2-mimetic treatment is indicated if functional factors predominate, whereby it appears essential to obtain the requisite experimental data for precise quantification of beta-mimetic action."}
{"id": "PMID:16409", "title": "[Physiology and biochemistry of streptomycetes. VIII. Esterase activity and production of turimycin in cultures of Streptomyces hygroscopicus JA 6599].", "content": "Esterase in cell-free extracts of Streptomyces hygroscopicus JA 6599 has a temperature-optimum of 35 degrees C, a pH-optimum with p-nitrophenylacetate as substrate at pH 7.7--8.1, with alpha-naphthylacetate at pH 7--9. Michaelis constants in cell-free extracts: with alpha-naphthylacetate Km = = 0.71 mM, with p-nitrophenylacetate Km = 0.21 mM. Phenylesters were better hydrolyzed than naphthylesters, phenylacetate was best hydrolyzed; beta-naphthylacetate was better hydrolyzed than alpha-naphthylacetate. Among the naphthylesters the ester of propionic acid was hydrolyzed best. Caprylate, stearate, and 0,0-diethyl-0-(p-nitrophenyl)-phosphate inhibit the splitting of alpha-naphthylacetate. A comparison with esterases of other biological origin shows that the enzyme studied can be a carboxylesterase (E.C.3.1.1.1.). In cultures of JA 6599 V13 and JA 6599-6 the change of esterase activity during the fermentation was determined. We found a carrelation between the enzymatic activity and the antibiotic-concentration in the culture medium.", "contents": "[Physiology and biochemistry of streptomycetes. VIII. Esterase activity and production of turimycin in cultures of Streptomyces hygroscopicus JA 6599]. Esterase in cell-free extracts of Streptomyces hygroscopicus JA 6599 has a temperature-optimum of 35 degrees C, a pH-optimum with p-nitrophenylacetate as substrate at pH 7.7--8.1, with alpha-naphthylacetate at pH 7--9. Michaelis constants in cell-free extracts: with alpha-naphthylacetate Km = = 0.71 mM, with p-nitrophenylacetate Km = 0.21 mM. Phenylesters were better hydrolyzed than naphthylesters, phenylacetate was best hydrolyzed; beta-naphthylacetate was better hydrolyzed than alpha-naphthylacetate. Among the naphthylesters the ester of propionic acid was hydrolyzed best. Caprylate, stearate, and 0,0-diethyl-0-(p-nitrophenyl)-phosphate inhibit the splitting of alpha-naphthylacetate. A comparison with esterases of other biological origin shows that the enzyme studied can be a carboxylesterase (E.C.3.1.1.1.). In cultures of JA 6599 V13 and JA 6599-6 the change of esterase activity during the fermentation was determined. We found a carrelation between the enzymatic activity and the antibiotic-concentration in the culture medium."}
{"id": "PMID:16400", "title": "[Effect of psychotropic preparations on the activity of Ca- and Mg-dependent ATPase of the sarcoplasmic reticulum].", "content": "In sarcoplasmic reticulum of rabbit skeletal muscles the activity of Ca2+, Mg2+- dependent ATPase was distinctly inhibited under effect of neuroleptic drugs - derivatives of phenothiazine and butyrophenone. The effect of tricyclic antidepressants was less pronounced. Tranquilizers (derivatives of 1,4-benzodiazepine) inhibited the enzyme, but trioxazin was only slightly active. High concentrations of lithium salts and of psychostimulants caffeine and corasole were found to stimulate the Ca2+, Mg2+-ATPase activity; low concentrations of the substances slightly inhibited the enzyme. The blocking effect of psychotropic drugs was more distinct, if the enzyme preparations were previously treated with ATP.", "contents": "[Effect of psychotropic preparations on the activity of Ca- and Mg-dependent ATPase of the sarcoplasmic reticulum]. In sarcoplasmic reticulum of rabbit skeletal muscles the activity of Ca2+, Mg2+- dependent ATPase was distinctly inhibited under effect of neuroleptic drugs - derivatives of phenothiazine and butyrophenone. The effect of tricyclic antidepressants was less pronounced. Tranquilizers (derivatives of 1,4-benzodiazepine) inhibited the enzyme, but trioxazin was only slightly active. High concentrations of lithium salts and of psychostimulants caffeine and corasole were found to stimulate the Ca2+, Mg2+-ATPase activity; low concentrations of the substances slightly inhibited the enzyme. The blocking effect of psychotropic drugs was more distinct, if the enzyme preparations were previously treated with ATP."}
{"id": "PMID:16401", "title": "[Use of potentiometric titration at constant pH for determination of the activity of lipoprotein lipase].", "content": "A method is developed for determination of the lipoprotein lipase activity. The method is based on the steady state potentiometric titration at constant pH value of higher fatty acids, liberated during the hydrolysis. An oil emulsion intralipid, activated by human blood serum, was used as a substrate. The sensitivity of the method was equal to 0.004-0.010 micronM of fatty acids per min. The reproducibility of the results was 2-5%. This simple and rapid method enabled to study kinetic of reactions, catalyzed by lipoprotein lipases.", "contents": "[Use of potentiometric titration at constant pH for determination of the activity of lipoprotein lipase]. A method is developed for determination of the lipoprotein lipase activity. The method is based on the steady state potentiometric titration at constant pH value of higher fatty acids, liberated during the hydrolysis. An oil emulsion intralipid, activated by human blood serum, was used as a substrate. The sensitivity of the method was equal to 0.004-0.010 micronM of fatty acids per min. The reproducibility of the results was 2-5%. This simple and rapid method enabled to study kinetic of reactions, catalyzed by lipoprotein lipases."}
{"id": "PMID:16410", "title": "NAD(P)H utilization in the reduction of pyruvate to lactate in a glycogen-containing subline of Ehrlich ascites tumour cells.", "content": "The possible pathways of utilization of glucose-6-phosphate (G-6-P) produced from glycogen breakdown have been investigated in a glycogen-containing subline of Ehrlich ascites tumour cells. Addition of either mitochondrial inhibitors or pyruvate to ascites cells metabolizing endogenous substrates enhances the rate of lactate production. However, only in the former condition such effect is abolished by iodoacetate (IAA). In pyruvate-supplemented cells mitochondrial inhibitors cause a further increase in lactate production which becomes insensitive to IAA when the cells are depleted of endogenous substrates. Measurements of the glycogen content show that either in the presence of mitochondrial inhibitors or pyruvate there is a stimulation of glycogenolysis. Significant changes (about 10--20 fold increase) of the G-6-P level are observed only in the presence of both mitochondrial inhibitors and IAA, irrespective of pyruvate addition. However, with pyruvate the accumulation of G-6-P becomes lower if the cells are starved. The results obtained indicate that in our conditions G-6-P which is produced during glycogenolysis may be oxidized either through the Embden-Meyerhof pathway or the phosphogluconate pathway. Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio.", "contents": "NAD(P)H utilization in the reduction of pyruvate to lactate in a glycogen-containing subline of Ehrlich ascites tumour cells. The possible pathways of utilization of glucose-6-phosphate (G-6-P) produced from glycogen breakdown have been investigated in a glycogen-containing subline of Ehrlich ascites tumour cells. Addition of either mitochondrial inhibitors or pyruvate to ascites cells metabolizing endogenous substrates enhances the rate of lactate production. However, only in the former condition such effect is abolished by iodoacetate (IAA). In pyruvate-supplemented cells mitochondrial inhibitors cause a further increase in lactate production which becomes insensitive to IAA when the cells are depleted of endogenous substrates. Measurements of the glycogen content show that either in the presence of mitochondrial inhibitors or pyruvate there is a stimulation of glycogenolysis. Significant changes (about 10--20 fold increase) of the G-6-P level are observed only in the presence of both mitochondrial inhibitors and IAA, irrespective of pyruvate addition. However, with pyruvate the accumulation of G-6-P becomes lower if the cells are starved. The results obtained indicate that in our conditions G-6-P which is produced during glycogenolysis may be oxidized either through the Embden-Meyerhof pathway or the phosphogluconate pathway. Indeed, whereas mitochondrial inhibitors promote the utilization of this metabolite through the first route by enhancing the activity of phosphofructokinase, added pyruvate favours the other route by lowering the cytosolic NADPH/NADP+ ratio."}
{"id": "PMID:16411", "title": "The effect of iron, tin, aluminium, and chromium on fading, discoloration, and precipitation in berry and red beet juices.", "content": "The effect of iron(II), tin(II), aluminium(III), and chromium(III) on the properties of red whortleberry, blackcurrant, and red beet juices was followed during storage for 10 months at 5 degrees C. The colour and pH changes were studied, and the precipitates formed were weighed and their metal contents assayed. Of the metals tested, only tin caused bluish discoloration in the berry juices. In the case of iron, aluminium, and chromium the low pH prevented this type of discoloration. In berry juices, some increases in colour intensity took place with the lowering of pH value, whereas in red beet juice the opposite change occurred. The colour changes due to storage appear to take place irrespective of the metals. Precipitation is enhanced in red whortleberry juice only by tin, and in blackcurrant juice by tin and iron. In red beet juice, precipitation is increased by the lowering of pH resulting from metal salt addition. In general, increase in the amount of metal added increased the metal content of the precipitate. Iron showed the greatest tendency to become bound in the precipitate, particularly in blackcurrant and red beet juice. The suitabilities of the metals for canning purposes are considered. Chromium, in particular, has interesting possibilities in view of the low degree of colour change associated with it.", "contents": "The effect of iron, tin, aluminium, and chromium on fading, discoloration, and precipitation in berry and red beet juices. The effect of iron(II), tin(II), aluminium(III), and chromium(III) on the properties of red whortleberry, blackcurrant, and red beet juices was followed during storage for 10 months at 5 degrees C. The colour and pH changes were studied, and the precipitates formed were weighed and their metal contents assayed. Of the metals tested, only tin caused bluish discoloration in the berry juices. In the case of iron, aluminium, and chromium the low pH prevented this type of discoloration. In berry juices, some increases in colour intensity took place with the lowering of pH value, whereas in red beet juice the opposite change occurred. The colour changes due to storage appear to take place irrespective of the metals. Precipitation is enhanced in red whortleberry juice only by tin, and in blackcurrant juice by tin and iron. In red beet juice, precipitation is increased by the lowering of pH resulting from metal salt addition. In general, increase in the amount of metal added increased the metal content of the precipitate. Iron showed the greatest tendency to become bound in the precipitate, particularly in blackcurrant and red beet juice. The suitabilities of the metals for canning purposes are considered. Chromium, in particular, has interesting possibilities in view of the low degree of colour change associated with it."}
{"id": "PMID:16412", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. V. Change in the diphosphatase activity of muscle post mortem (author's transl)].", "content": "The diphosphatase (DPase) activity of minced bovine muscle decreased during storage of the intact muscle post mortem (p.m.) but there was only little change after development of rigor mortis. The drop in pH p.m. seems to be not the only reason for the decrease in DPase activity. In the postrigor muscle the DPase activity, measured at pH greater than 6, increased during the breakdown of DP. The rise of activity was the slower the longer the muscle was stored. The result of a mathematical regression analysis, developed for the kinetic study of this anomaly in the breakdown of DP, indicates that a certain mechanism of activation of the initially inactive DPase in muscle exists.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. V. Change in the diphosphatase activity of muscle post mortem (author's transl)]. The diphosphatase (DPase) activity of minced bovine muscle decreased during storage of the intact muscle post mortem (p.m.) but there was only little change after development of rigor mortis. The drop in pH p.m. seems to be not the only reason for the decrease in DPase activity. In the postrigor muscle the DPase activity, measured at pH greater than 6, increased during the breakdown of DP. The rise of activity was the slower the longer the muscle was stored. The result of a mathematical regression analysis, developed for the kinetic study of this anomaly in the breakdown of DP, indicates that a certain mechanism of activation of the initially inactive DPase in muscle exists."}
{"id": "PMID:16413", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. VI. Influence of pH on the tripolyphosphatase and diphosphatase activities in bovine muscle (author's transl)].", "content": "The pH optimum of the tripolyphosphatase activity of minced bovine muscle post rigor was 5.6. The pH optimum of the diphosphatase activity was in the range between pH 6.7 and 6.8. The prolonged influence of pH values around 7 caused an additional increase in the diphosphatase activity.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. VI. Influence of pH on the tripolyphosphatase and diphosphatase activities in bovine muscle (author's transl)]. The pH optimum of the tripolyphosphatase activity of minced bovine muscle post rigor was 5.6. The pH optimum of the diphosphatase activity was in the range between pH 6.7 and 6.8. The prolonged influence of pH values around 7 caused an additional increase in the diphosphatase activity."}
{"id": "PMID:16416", "title": "[Gluconic acid forming enzymes in Aspergillus niger (author's transl)].", "content": "At least three gluconic acid forming enzymes were identified in cell-free extracts of Aspergillus niger: glucose oxidase (EC 1.1.3.4), a glucose dehydrogenase (EC 1.1.99.10), and an enzyme or a mixture of enzymes catalyzing the cleavage of 6-phosphogluconate into gluconate and inorganic phosphate. 2,6-dichlorphenolindophenol was one of the hydrogen acceptors in vitro of the glucose dehydrogenase. Some properties of this enzyme (Km values, pH-dependence, substrate and hydrogen acceptor specificity), as determined in cell-free extracts, were found to be in good agreement with properties described in literature for a glucose dehydrogenase which has been purified from Aspergillus oryzae. The formation of Pi from 6-phosphogluconate and other phosphate esters was found to have an optimum between pH 7 and 8 , and another below pH 4. This suggests that it is catalyzed by an alkaline and an acid phosphomonoesterase (EC 3.1.3.1, 3.1.3.2), both enzymes exhibiting only low substrate specificity. The influence of extraction and assay buffers on the activity of gluconate forming enzymes was investigated. Loss of activity during preparation of cell-free extracts, as calculated from loss of activity storage of cell-free extracts at 4 degrees C, was found to be lower than 4%. Purified glucose oxidase added before homogenization was found in the extract almost quantitatively.", "contents": "[Gluconic acid forming enzymes in Aspergillus niger (author's transl)]. At least three gluconic acid forming enzymes were identified in cell-free extracts of Aspergillus niger: glucose oxidase (EC 1.1.3.4), a glucose dehydrogenase (EC 1.1.99.10), and an enzyme or a mixture of enzymes catalyzing the cleavage of 6-phosphogluconate into gluconate and inorganic phosphate. 2,6-dichlorphenolindophenol was one of the hydrogen acceptors in vitro of the glucose dehydrogenase. Some properties of this enzyme (Km values, pH-dependence, substrate and hydrogen acceptor specificity), as determined in cell-free extracts, were found to be in good agreement with properties described in literature for a glucose dehydrogenase which has been purified from Aspergillus oryzae. The formation of Pi from 6-phosphogluconate and other phosphate esters was found to have an optimum between pH 7 and 8 , and another below pH 4. This suggests that it is catalyzed by an alkaline and an acid phosphomonoesterase (EC 3.1.3.1, 3.1.3.2), both enzymes exhibiting only low substrate specificity. The influence of extraction and assay buffers on the activity of gluconate forming enzymes was investigated. Loss of activity during preparation of cell-free extracts, as calculated from loss of activity storage of cell-free extracts at 4 degrees C, was found to be lower than 4%. Purified glucose oxidase added before homogenization was found in the extract almost quantitatively."}
{"id": "PMID:16418", "title": "The fermentative production of acetone-butanol by Clostridium acetobutylicum.", "content": "Fourteen different media were used in the fermentative production of acetone-butanol. The highest total yields were achieved in medium I. Potato starch and soluble starch were suitable as carbon sources. The best concentrations of potato starch and soluble starch were 500.0 and 10.0 g/l, respectively. Peptone was the most favourable nitrogen source. The best concentration of peptone was 4.0 g/l. Calcium carbonate in 3.6 g/l acted as buffering agent in the fermentation process. The best initial pH value of the fermentation medium was 6.0. The optimum temperature was 32--33degreesC. The fermentation process required 120 h to obtain maximum yields of acetone-butanol.", "contents": "The fermentative production of acetone-butanol by Clostridium acetobutylicum. Fourteen different media were used in the fermentative production of acetone-butanol. The highest total yields were achieved in medium I. Potato starch and soluble starch were suitable as carbon sources. The best concentrations of potato starch and soluble starch were 500.0 and 10.0 g/l, respectively. Peptone was the most favourable nitrogen source. The best concentration of peptone was 4.0 g/l. Calcium carbonate in 3.6 g/l acted as buffering agent in the fermentation process. The best initial pH value of the fermentation medium was 6.0. The optimum temperature was 32--33degreesC. The fermentation process required 120 h to obtain maximum yields of acetone-butanol."}
{"id": "PMID:16419", "title": "Histomorphology and proteolytic activity in the gastric apparatus of frugivorous, carnivorous and omnivorous species of birds.", "content": "The histomorphology of the gastric apparatus, the pepsin level and the optimum pH for pepsin were investigated in Psittacula krameri (frugivore), Lanius schach (carnivore) and Acridotheres tristis (omnivore) species of birds. The proventricular glands were found to be made up of oxynticopeptic cells. The lobules of the oxynticopeptic cells are polyhedral; they are the largest in P. krameri, and the smallest in A. tristis. However, their greater number in A. tristis enables a higher secretion of hydrochloric acid and pepsin. The villi are more developed in A. tristis than in L. schach and P. krameri. The gizzard is larger in A. tristis than in P. krameri and A. tritis than in the carnivore L. schach. Koilin lining is beset with horny cones, which were well developed in A. tristis, moderately developed in P. krameri and absent in L. schach. The pepsin activity is higher in the proventriculus of the carnivorous L. schach and the omnivorous A. tristis than in the frugivorous P. krameri. Slight pepsin activity was also observed in gizzard tissue extracts in all the three species. The optimum pH for pepsin was found to be 1.5 for P. krameri and 1.8 for both L. schach and A. tristis.", "contents": "Histomorphology and proteolytic activity in the gastric apparatus of frugivorous, carnivorous and omnivorous species of birds. The histomorphology of the gastric apparatus, the pepsin level and the optimum pH for pepsin were investigated in Psittacula krameri (frugivore), Lanius schach (carnivore) and Acridotheres tristis (omnivore) species of birds. The proventricular glands were found to be made up of oxynticopeptic cells. The lobules of the oxynticopeptic cells are polyhedral; they are the largest in P. krameri, and the smallest in A. tristis. However, their greater number in A. tristis enables a higher secretion of hydrochloric acid and pepsin. The villi are more developed in A. tristis than in L. schach and P. krameri. The gizzard is larger in A. tristis than in P. krameri and A. tritis than in the carnivore L. schach. Koilin lining is beset with horny cones, which were well developed in A. tristis, moderately developed in P. krameri and absent in L. schach. The pepsin activity is higher in the proventriculus of the carnivorous L. schach and the omnivorous A. tristis than in the frugivorous P. krameri. Slight pepsin activity was also observed in gizzard tissue extracts in all the three species. The optimum pH for pepsin was found to be 1.5 for P. krameri and 1.8 for both L. schach and A. tristis."}
{"id": "PMID:16420", "title": "Phospholipase C from Bacillus cereus. Action on some artificial lecithins.", "content": "The hydrolysis by phospholipase C from B. cereus of several lecithins of different fatty acyl chain length was examined. The enzyme showed significant activity towards mono-molecularly dispersed short chain lecithins and the reaction obeyed normal Michaelis-Menten kinetics. Rate vs. substrate concentration curves obtained with dihexanoyl-, diheptanoyl- and dioctanoyllecithins showed marked discontinuities in the region of the known critical micelle concentrations for these substrates and distinctly higher rates were obtained just above these levels. Using these three lecithins at levels below their respective critical micelle concentrations, rate increases were noted if the reactions were allowed to proceed to a sufficiently great extent. The presence of deoxycholate in the reaction system had little or no effect on the rate of enzyme-catalysed hydrolysis of lecithins of fatty acyl chain length less than or equal to Cbeta, but for fatty acyl chain lengths greater than C10, significant rate increases occurred. The pH profile for the enzyme activity was also examined.", "contents": "Phospholipase C from Bacillus cereus. Action on some artificial lecithins. The hydrolysis by phospholipase C from B. cereus of several lecithins of different fatty acyl chain length was examined. The enzyme showed significant activity towards mono-molecularly dispersed short chain lecithins and the reaction obeyed normal Michaelis-Menten kinetics. Rate vs. substrate concentration curves obtained with dihexanoyl-, diheptanoyl- and dioctanoyllecithins showed marked discontinuities in the region of the known critical micelle concentrations for these substrates and distinctly higher rates were obtained just above these levels. Using these three lecithins at levels below their respective critical micelle concentrations, rate increases were noted if the reactions were allowed to proceed to a sufficiently great extent. The presence of deoxycholate in the reaction system had little or no effect on the rate of enzyme-catalysed hydrolysis of lecithins of fatty acyl chain length less than or equal to Cbeta, but for fatty acyl chain lengths greater than C10, significant rate increases occurred. The pH profile for the enzyme activity was also examined."}
{"id": "PMID:16423", "title": "Inactivation of somatostatin by peptidases in different areas of the rat brain.", "content": "With the availability of a sensitive and specific radioimmunoassay for growth hormone-release-inhibiting hormone (somatostatin or GH-RIH), it has been possible to investigate the presence of peptidase enzymes capable of inactivating this hypothalamic hormone in the hypothalamus and other brain areas of the rat. It was found that both supernatant and particulate fractions from male rat hypothalami rapidly inactivated somatostatin and that the enzymes involved have an optimum pH of 7.3. Peptidase activity was significantly higher in the supernatant than in the particulate fraction from the hypothalamus, thalamus, cortex and cerebellum. Besides confirming the presence of peptidases inactivating the release-inhibiting hormone in the hypothalamus (the site of somatostatin synthesis and release), the results may indicate that somatostatin has a functional significance outside the hypothalamus-anterior pituitary axis but within the central nervous system.", "contents": "Inactivation of somatostatin by peptidases in different areas of the rat brain. With the availability of a sensitive and specific radioimmunoassay for growth hormone-release-inhibiting hormone (somatostatin or GH-RIH), it has been possible to investigate the presence of peptidase enzymes capable of inactivating this hypothalamic hormone in the hypothalamus and other brain areas of the rat. It was found that both supernatant and particulate fractions from male rat hypothalami rapidly inactivated somatostatin and that the enzymes involved have an optimum pH of 7.3. Peptidase activity was significantly higher in the supernatant than in the particulate fraction from the hypothalamus, thalamus, cortex and cerebellum. Besides confirming the presence of peptidases inactivating the release-inhibiting hormone in the hypothalamus (the site of somatostatin synthesis and release), the results may indicate that somatostatin has a functional significance outside the hypothalamus-anterior pituitary axis but within the central nervous system."}
{"id": "PMID:16424", "title": "Corticotrophic and melanotrophic functions in congenital adrenal hyperplasia.", "content": "In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and beta-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor). The results indicate a significant increase in plasma ACTH and beta-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and beta-MSH levels, in some only the plasma ACTH values were high and beta-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provcative tests. Lastly, it must be emphasized that no modifications of plasma beta-MSH after synthetic MIF infusion were found in subject with normal or high plasma beta-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man.", "contents": "Corticotrophic and melanotrophic functions in congenital adrenal hyperplasia. In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and beta-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor). The results indicate a significant increase in plasma ACTH and beta-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and beta-MSH levels, in some only the plasma ACTH values were high and beta-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provcative tests. Lastly, it must be emphasized that no modifications of plasma beta-MSH after synthetic MIF infusion were found in subject with normal or high plasma beta-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man."}
{"id": "PMID:16425", "title": "Complex of D-glyceraldehyde-3-phosphate dehydrogenase with Cu2+ ion. The properties of ternary Cu-enzyme-coenzyme complex.", "content": "The formation of ternary Cu-enzyme-coenzyme complex from cupric ion and D-glyceraldehyde-3-phosphate dehydrogenase holoenzyme results in similar spectral changes as the formation of binary Cu-apoenzyme complex, which indicates that the complex bonds between cupric ion and the holoenzyme, and cupric ion and the apoenzyme are similar. Spectrophotometric titration, chemical modification experiments and inhibition studies with cupric ion gave evidence that cupric ion is selectively bound on Cys-149 residue also in the Cu-GAPD-NAD complex. The charge transfer interaction between the coenzyme and Cu-GAPD, i.e. the difference spectrum of the combination of NAD with Cu-GAPD complex, is different from that of the enzyme-coenzyme complex in the absence of cupric ion. The shape of this \"modified enzyme-coenzyme charge transfer spectrum\" is influenced by various anions. The difference absorption does not depend on the pH in the range of 5.5 to 9. This indicates that the bound cupric ion abolishes the effect of deprotonation of a functional group in the protein on the charge transfer interaction. It is suggested that this functional group is a histidine imidazole, which activates the Cys-149 thiol group in the native enzyme and binds the metal ion in the cupric complex in a Cys-Cu-His chelate structure.", "contents": "Complex of D-glyceraldehyde-3-phosphate dehydrogenase with Cu2+ ion. The properties of ternary Cu-enzyme-coenzyme complex. The formation of ternary Cu-enzyme-coenzyme complex from cupric ion and D-glyceraldehyde-3-phosphate dehydrogenase holoenzyme results in similar spectral changes as the formation of binary Cu-apoenzyme complex, which indicates that the complex bonds between cupric ion and the holoenzyme, and cupric ion and the apoenzyme are similar. Spectrophotometric titration, chemical modification experiments and inhibition studies with cupric ion gave evidence that cupric ion is selectively bound on Cys-149 residue also in the Cu-GAPD-NAD complex. The charge transfer interaction between the coenzyme and Cu-GAPD, i.e. the difference spectrum of the combination of NAD with Cu-GAPD complex, is different from that of the enzyme-coenzyme complex in the absence of cupric ion. The shape of this \"modified enzyme-coenzyme charge transfer spectrum\" is influenced by various anions. The difference absorption does not depend on the pH in the range of 5.5 to 9. This indicates that the bound cupric ion abolishes the effect of deprotonation of a functional group in the protein on the charge transfer interaction. It is suggested that this functional group is a histidine imidazole, which activates the Cys-149 thiol group in the native enzyme and binds the metal ion in the cupric complex in a Cys-Cu-His chelate structure."}
{"id": "PMID:16428", "title": "The testing of the antibiotic sensitivity of bacteria on an agar medium: The problem of a double zone of inhibition.", "content": "When the sensitivity of Micrococcus luteus ATTC9341 to streptomycin, erythromycin, oleandomycin and spiramycin was tested by an agar diffusion method using antibiotic impregnated filter paper disks on unbuffered Penassay Seed Agar two zones of inhibition were observed around the disks after an incubation period of 24 hours at 30 degrees C. The pH of the M. luteus seeded Penassay Seed Agar was measured before and after 24 hours incubation at 30 degrees C and found to be 6.6 and 8.7, respectively. When the Penassay Seed Agar was buffered to pH 6.1 and the sensitivity of the microbe to the antibiotics was tested as before no double zones of inhibition could be observed. The phenomenon of the double zones of inhibition may possibly be due to the pH increase of the medium from a relatively low level to the optimum range of activities of the antibiotics during the incubation period.", "contents": "The testing of the antibiotic sensitivity of bacteria on an agar medium: The problem of a double zone of inhibition. When the sensitivity of Micrococcus luteus ATTC9341 to streptomycin, erythromycin, oleandomycin and spiramycin was tested by an agar diffusion method using antibiotic impregnated filter paper disks on unbuffered Penassay Seed Agar two zones of inhibition were observed around the disks after an incubation period of 24 hours at 30 degrees C. The pH of the M. luteus seeded Penassay Seed Agar was measured before and after 24 hours incubation at 30 degrees C and found to be 6.6 and 8.7, respectively. When the Penassay Seed Agar was buffered to pH 6.1 and the sensitivity of the microbe to the antibiotics was tested as before no double zones of inhibition could be observed. The phenomenon of the double zones of inhibition may possibly be due to the pH increase of the medium from a relatively low level to the optimum range of activities of the antibiotics during the incubation period."}
{"id": "PMID:16429", "title": "Effect of propranolol and related drugs on transmembraneous pH differences in liposomes.", "content": "Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a beta-adrenergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane.", "contents": "Effect of propranolol and related drugs on transmembraneous pH differences in liposomes. Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a beta-adrenergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane."}
{"id": "PMID:16430", "title": "On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long-term administration.", "content": "The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment.", "contents": "On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long-term administration. The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment."}
{"id": "PMID:16426", "title": "[Measurement of transport in mucous membrane in the human nose with Cr-51-labeled resin beads].", "content": "The mucociliary transport of the human nasal mucosa was studied by using very small resin beads tagged with 51Cr. Several modifications of previous methods were introduced, e.g. kind of nuclide, particle size, pH, mode of application, measuring technique and reduction of local irradiation. Finally arrangements implying exact measurements of transport not only horizontally but also vertically or obliquely were obtained. No mucociliary transport was demonstrated in five of nine subjects with a common cold 10 days before or one week after the investigation. Xylometazolin as a nasal spray diminished the mucociliary transport significantly. In addition, the effects on mucociliary transport caused by homolateral or contralateral experimental nasal obstruction as well as by tobacco smoking were studied in healthy subjects. Finally, patients with various diseases: pollen allergy in free intervals, chronic rhinitis, septal deviation or perforation, and condition after laryngectomy were also investigated.", "contents": "[Measurement of transport in mucous membrane in the human nose with Cr-51-labeled resin beads]. The mucociliary transport of the human nasal mucosa was studied by using very small resin beads tagged with 51Cr. Several modifications of previous methods were introduced, e.g. kind of nuclide, particle size, pH, mode of application, measuring technique and reduction of local irradiation. Finally arrangements implying exact measurements of transport not only horizontally but also vertically or obliquely were obtained. No mucociliary transport was demonstrated in five of nine subjects with a common cold 10 days before or one week after the investigation. Xylometazolin as a nasal spray diminished the mucociliary transport significantly. In addition, the effects on mucociliary transport caused by homolateral or contralateral experimental nasal obstruction as well as by tobacco smoking were studied in healthy subjects. Finally, patients with various diseases: pollen allergy in free intervals, chronic rhinitis, septal deviation or perforation, and condition after laryngectomy were also investigated."}
{"id": "PMID:16436", "title": "Distribution of coronary blood flow in the left ventricular wall of dogs evaluated by the uptake of Xe-133.", "content": "The distribution of coronary blood flow was estimated in anesthetized dogs by counting the activity in tissue blocks of the left ventricular free wall immediately after bolus injection of Xe-133 into the aortic root. No differences in the uptake of isotope were observed between the apex and the base of the heart; between areas supplied by the anterior descending and circumflex branches of the left coronary artery; or between the endo- and epicardial halves of the wall. In most experiments a bolus injection of the isotope into the left coronary artery was followed by a difference in activity between areas supplied by the left anterior descending and left circumflex branches. This indicated inadequate mixing of blood and isotope in the main stem of the artery. The uneven distribution did not result in differences between the epi- and endocardial activity concentrations. The results from one normal, anesthetized dog in which tissue activities were measured after constant rate infusion of Xe-133 into the left coronary artery for 8 min were in accordance with the general assumption of equal epi- and endocardial volumes of distribution (values of lambda).", "contents": "Distribution of coronary blood flow in the left ventricular wall of dogs evaluated by the uptake of Xe-133. The distribution of coronary blood flow was estimated in anesthetized dogs by counting the activity in tissue blocks of the left ventricular free wall immediately after bolus injection of Xe-133 into the aortic root. No differences in the uptake of isotope were observed between the apex and the base of the heart; between areas supplied by the anterior descending and circumflex branches of the left coronary artery; or between the endo- and epicardial halves of the wall. In most experiments a bolus injection of the isotope into the left coronary artery was followed by a difference in activity between areas supplied by the left anterior descending and left circumflex branches. This indicated inadequate mixing of blood and isotope in the main stem of the artery. The uneven distribution did not result in differences between the epi- and endocardial activity concentrations. The results from one normal, anesthetized dog in which tissue activities were measured after constant rate infusion of Xe-133 into the left coronary artery for 8 min were in accordance with the general assumption of equal epi- and endocardial volumes of distribution (values of lambda)."}
{"id": "PMID:16437", "title": "The ability of ATP-free granule material from bovine adrenal medulla to bind inorganic cations and biogenic amines.", "content": "Bovine adrenal medullary granules isolated by millipore filtration were depleted of CA and ATP by dialysis. The resulting material showed an ability to bind inorganic cations and biogenic amines in a concentration-dependent manner. The similarity of the uptake curves, the identical uptake maxima and the narrow pH range (between 4-7) over which the uptake of the inorganic and organic cations took place indicated a binding of these ions to common sites. In addition, the fact that all the uptake curves fitted the Rothmund-Kornfeld equation for cation exchangers corroborated the cation exchanger properties of the dialyzed granule material. The CA binding capacity corresponded to 20-30% of the normal CA content of bovine medullary granules.", "contents": "The ability of ATP-free granule material from bovine adrenal medulla to bind inorganic cations and biogenic amines. Bovine adrenal medullary granules isolated by millipore filtration were depleted of CA and ATP by dialysis. The resulting material showed an ability to bind inorganic cations and biogenic amines in a concentration-dependent manner. The similarity of the uptake curves, the identical uptake maxima and the narrow pH range (between 4-7) over which the uptake of the inorganic and organic cations took place indicated a binding of these ions to common sites. In addition, the fact that all the uptake curves fitted the Rothmund-Kornfeld equation for cation exchangers corroborated the cation exchanger properties of the dialyzed granule material. The CA binding capacity corresponded to 20-30% of the normal CA content of bovine medullary granules."}
{"id": "PMID:16438", "title": "Effect of hypercapnia and hypocapnia on tryptophan and tyrosine hydroxylation in rat brain.", "content": "The effects of induced hypo- and hypercapnia upon the rate of hydroxylation of tryptophan and tyrosine in the rat brain were studied by measuring the accumulation of 5-HTP and DOPA following administration of the aromatic L-aminoacid decarboxylase inhibitor 3-hydroxybenzylhydrazine HCl (NSD 1015). The results suggest that the hydroxylation of tryptophan varies directly with the tissue Po2. On the other hand, the hydroxylation of tyrosine did not show a simple relationship to Po2 but appeared to be influenced by pH changes.", "contents": "Effect of hypercapnia and hypocapnia on tryptophan and tyrosine hydroxylation in rat brain. The effects of induced hypo- and hypercapnia upon the rate of hydroxylation of tryptophan and tyrosine in the rat brain were studied by measuring the accumulation of 5-HTP and DOPA following administration of the aromatic L-aminoacid decarboxylase inhibitor 3-hydroxybenzylhydrazine HCl (NSD 1015). The results suggest that the hydroxylation of tryptophan varies directly with the tissue Po2. On the other hand, the hydroxylation of tyrosine did not show a simple relationship to Po2 but appeared to be influenced by pH changes."}
{"id": "PMID:16439", "title": "Angiography of the testicular artery. II. Cryptorchism and testicular agenesis.", "content": "A selective angiography of the testicular artery was performed in 7 boys and 7 men without a palpable testicle in order to localize cryptorchid testes or to establish testicular agenesis. The examination could be carried out in all cases, and the angiographic diagnosis was confirmed at operation and at a subsequent microscopy in the 12 cases hitherto operated upon. The width of the artery and its branches are also presented.", "contents": "Angiography of the testicular artery. II. Cryptorchism and testicular agenesis. A selective angiography of the testicular artery was performed in 7 boys and 7 men without a palpable testicle in order to localize cryptorchid testes or to establish testicular agenesis. The examination could be carried out in all cases, and the angiographic diagnosis was confirmed at operation and at a subsequent microscopy in the 12 cases hitherto operated upon. The width of the artery and its branches are also presented."}
{"id": "PMID:16453", "title": "Factors affecting urate reabsorption in the rat kidney.", "content": "1. Urate transport in the rat appears to be saturable. However, affinity of the transport system for urate is very low and transport far from saturated at physiological plasma concentrations. 2. Since increase of the nonionized fraction of uric acid by a factor of five failed to increase urate reabsorption, transport cannot be due to nonionic diffusion but rather involves ionized urate. 3. Increases in luminal flow rate markedly depress urate reabsorption in the loop of Henle, which results in wash out of medullary urate.", "contents": "Factors affecting urate reabsorption in the rat kidney. 1. Urate transport in the rat appears to be saturable. However, affinity of the transport system for urate is very low and transport far from saturated at physiological plasma concentrations. 2. Since increase of the nonionized fraction of uric acid by a factor of five failed to increase urate reabsorption, transport cannot be due to nonionic diffusion but rather involves ionized urate. 3. Increases in luminal flow rate markedly depress urate reabsorption in the loop of Henle, which results in wash out of medullary urate."}
{"id": "PMID:16456", "title": "Uric acid transport characteristics in human erythrocytes.", "content": "Taken all together the results show that the RBC transport of U.A. seems to be partly of passive nature, closely similar to others mineral or organic anions, and partly of active nature related to compound of the membrane playing a role in cellular metabolism. It remains to be precised the role of the membrane itself and to characterize the membrane site which could be responsible of a part of the transport of U.A. through erythrocyte membrane.", "contents": "Uric acid transport characteristics in human erythrocytes. Taken all together the results show that the RBC transport of U.A. seems to be partly of passive nature, closely similar to others mineral or organic anions, and partly of active nature related to compound of the membrane playing a role in cellular metabolism. It remains to be precised the role of the membrane itself and to characterize the membrane site which could be responsible of a part of the transport of U.A. through erythrocyte membrane."}
{"id": "PMID:16463", "title": "The pressor activity of burimamide: a relationship between chemical constitution and pressor activity of burimamide and related histamine H2-receptor antagonists.", "content": "Burimamide, a histamine H2-receptor antagonist, has been shown to cause pressor responses in pithed rats. The response can be prevented by prior removal of the adrenal glands or by pretreatment with the alpha-adrenoceptor antagonist, phentolamine, 5 mg/kg, suggesting that the pressor response to burimamide is due to release of catecholamines from the adrenal glands. The pressor activity of burimamide has been compared with that of metiamide and two close chemical analogues, methylburimamide and thiaburimamide, in order to identify which chemical features of the compounds are necessary for this activity. Methylburimamide was the most potent pressor agent, followed by burimamide, metiamide and thiaburimamide. The pressor effects (and presumably catecholamine-releasing activities) appear to be related to the basicities of the compounds. We conclude that the release of catecholamines by these histamine H2-receptor antagonists is probably due to their cationic (imidazolium) forms.", "contents": "The pressor activity of burimamide: a relationship between chemical constitution and pressor activity of burimamide and related histamine H2-receptor antagonists. Burimamide, a histamine H2-receptor antagonist, has been shown to cause pressor responses in pithed rats. The response can be prevented by prior removal of the adrenal glands or by pretreatment with the alpha-adrenoceptor antagonist, phentolamine, 5 mg/kg, suggesting that the pressor response to burimamide is due to release of catecholamines from the adrenal glands. The pressor activity of burimamide has been compared with that of metiamide and two close chemical analogues, methylburimamide and thiaburimamide, in order to identify which chemical features of the compounds are necessary for this activity. Methylburimamide was the most potent pressor agent, followed by burimamide, metiamide and thiaburimamide. The pressor effects (and presumably catecholamine-releasing activities) appear to be related to the basicities of the compounds. We conclude that the release of catecholamines by these histamine H2-receptor antagonists is probably due to their cationic (imidazolium) forms."}
{"id": "PMID:16465", "title": "A new semi-defined medium for Trypanosoma brucei sspp.", "content": "A new, easy to prepare semi-defined medium for the cultivation of trypanosomes of the T. brucei complex is introduced. Containing the two commercially available media MEM (Minimum Essential Medium) and Medium 199 TC45 as well as 10% inactivated foetal calf serum (fcs), the medium supports optimum growth and direct adaptation of bloodstream forms. Growth characteristics, glucose uptake, amino acid utilization and the ultrastructure of trypanosomes grown in this medium are described briefly.", "contents": "A new semi-defined medium for Trypanosoma brucei sspp. A new, easy to prepare semi-defined medium for the cultivation of trypanosomes of the T. brucei complex is introduced. Containing the two commercially available media MEM (Minimum Essential Medium) and Medium 199 TC45 as well as 10% inactivated foetal calf serum (fcs), the medium supports optimum growth and direct adaptation of bloodstream forms. Growth characteristics, glucose uptake, amino acid utilization and the ultrastructure of trypanosomes grown in this medium are described briefly."}
{"id": "PMID:16466", "title": "Anaemia in trypanosomiasis: mechanisms of erythrocyte destruction in mice infected with Trypanosoma congolense or T. brucei.", "content": "Studies in mice infected with T. brucei or T. congolense showed that increased red cell destruction in the spleen occurred as from the third day of patent parasitaemia and this resulted in a marked reduction of the half-life of transfused syngeneic 51Cr labelled cells. There was a progressive increase in the osmotic fragility of the red cells, especially in T. congolense infected mice which also showed a more severe anaemia. The antiglobulin test was only rarely positive in the late stages of T. brucei infection. Incubation of normal red cells with plasma from infected mice in vitro did not result in haemolysis, but in the case of plasma from T. brucei infected mice, it caused an appreciable reduction in the half-life of the cells when transfused into normal mice. It is suggested that mechanisms of red cell destruction in trypanosome infections are complex and may vary with the species of trypanosomes, the host and the stage of infection.", "contents": "Anaemia in trypanosomiasis: mechanisms of erythrocyte destruction in mice infected with Trypanosoma congolense or T. brucei. Studies in mice infected with T. brucei or T. congolense showed that increased red cell destruction in the spleen occurred as from the third day of patent parasitaemia and this resulted in a marked reduction of the half-life of transfused syngeneic 51Cr labelled cells. There was a progressive increase in the osmotic fragility of the red cells, especially in T. congolense infected mice which also showed a more severe anaemia. The antiglobulin test was only rarely positive in the late stages of T. brucei infection. Incubation of normal red cells with plasma from infected mice in vitro did not result in haemolysis, but in the case of plasma from T. brucei infected mice, it caused an appreciable reduction in the half-life of the cells when transfused into normal mice. It is suggested that mechanisms of red cell destruction in trypanosome infections are complex and may vary with the species of trypanosomes, the host and the stage of infection."}
{"id": "PMID:16467", "title": "Susceptibility of a rodent-adapted strain of Trypanosoma vivax to Berenil, Samorin and Novidium.", "content": "The susceptibility of a rodent-adapted strain of Trypanosoma vivax (Leeflant strain Y58) to Berenil, Samorin and Novidium was tested in mice. When infected mice were treated on the second day of detectable parasitaemia, there was complete cure with Berenil at 10 mg/kg, Novidium at 4 mg/kg and Samorin at 0.2 mg/kg body weight respectively. Berenil and Novodium at lower doses rendered the mice aparasitaemic for a few days followed by heavy parasitaemia (relapse) and death. Lower doses of Samorin, on the other hand, were curative for none or only some of the mice but without relapses. These observations are related to the accepted modes of action of these drugs and their use in the field.", "contents": "Susceptibility of a rodent-adapted strain of Trypanosoma vivax to Berenil, Samorin and Novidium. The susceptibility of a rodent-adapted strain of Trypanosoma vivax (Leeflant strain Y58) to Berenil, Samorin and Novidium was tested in mice. When infected mice were treated on the second day of detectable parasitaemia, there was complete cure with Berenil at 10 mg/kg, Novidium at 4 mg/kg and Samorin at 0.2 mg/kg body weight respectively. Berenil and Novodium at lower doses rendered the mice aparasitaemic for a few days followed by heavy parasitaemia (relapse) and death. Lower doses of Samorin, on the other hand, were curative for none or only some of the mice but without relapses. These observations are related to the accepted modes of action of these drugs and their use in the field."}
{"id": "PMID:16468", "title": "Observations on the feeding and defecation patterns of three triatomine species (Hemiptera: Reduviidae).", "content": "A comparative laboratory study of feeding and defecation behavior of three species of tritomines (Rhodnius prolixus, Triatoma infestans and T. dimidiata) indicated evident differences among the species and among the different stages of same species. Time required for a full blood meal was related to the size of the specimen. Insects required an average of 11-28 min for engorgement although some finished within 10 min. T. dimidata frequently interrupted the act of feeding, a probable explanation of the higher number of defecations before finishing a blood meal observed in the species. R. prolixus was superior to the other two species in number of defecating insects and in rapidity and frequency of defecations within a given time. T. dimidiata was inferior in all three parameters and T. infestans was intermediate. Males of all species tended to be less effective. A \"defecation index\" is proposed for comparing this different behavior in triatomine specimens under standard conditions. Effectivity of the insects according to the measured parameters is discussed in relation to the prevalence of Chagas' disease in those areas where they are principal vectors.", "contents": "Observations on the feeding and defecation patterns of three triatomine species (Hemiptera: Reduviidae). A comparative laboratory study of feeding and defecation behavior of three species of tritomines (Rhodnius prolixus, Triatoma infestans and T. dimidiata) indicated evident differences among the species and among the different stages of same species. Time required for a full blood meal was related to the size of the specimen. Insects required an average of 11-28 min for engorgement although some finished within 10 min. T. dimidata frequently interrupted the act of feeding, a probable explanation of the higher number of defecations before finishing a blood meal observed in the species. R. prolixus was superior to the other two species in number of defecating insects and in rapidity and frequency of defecations within a given time. T. dimidiata was inferior in all three parameters and T. infestans was intermediate. Males of all species tended to be less effective. A \"defecation index\" is proposed for comparing this different behavior in triatomine specimens under standard conditions. Effectivity of the insects according to the measured parameters is discussed in relation to the prevalence of Chagas' disease in those areas where they are principal vectors."}
{"id": "PMID:16470", "title": "Comparison of infectivity of Trypanosoma cruzi blood stream trypomastigotes and metacyclic trypomastigotes from Rhodnius prolixus.", "content": "Four strains of Trypanosoma cruzi (Y, BG, M and Peru) retain their ability to infect Rhodnius prolixus and to produce virulent infections in mice for from 12 to 39 years. About 60 or more metacyclic trypomastigotes were consistently lethal to mice. The mean number of metacyclics per bug ranged from 1.2 to 17.3 x 10(3). Comparative studies of virulence of metacyclics and blood trypomastigotes showed the blood forms to be slightly more virulent. The route of injection was shown to be more significant in varying the host response to infection, subcutaneous inoculation being the preferred route.", "contents": "Comparison of infectivity of Trypanosoma cruzi blood stream trypomastigotes and metacyclic trypomastigotes from Rhodnius prolixus. Four strains of Trypanosoma cruzi (Y, BG, M and Peru) retain their ability to infect Rhodnius prolixus and to produce virulent infections in mice for from 12 to 39 years. About 60 or more metacyclic trypomastigotes were consistently lethal to mice. The mean number of metacyclics per bug ranged from 1.2 to 17.3 x 10(3). Comparative studies of virulence of metacyclics and blood trypomastigotes showed the blood forms to be slightly more virulent. The route of injection was shown to be more significant in varying the host response to infection, subcutaneous inoculation being the preferred route."}
{"id": "PMID:16471", "title": "Immunization against Trypanosoma cruzi using killed antigens and with saponin as adjuvant.", "content": "The immunization of mice with killed epimastigotes or trypomastigotes with saponin SPL as adjuvant was challenged by inoculation of blood or metacyclic trypomastigotes of T. cruzi. Immunogenic preparations were obtained by freeze-thawing of formalin treatment. The protection was effective against homologous and heterologous challenge, and lasted up to 12 weeks after the last immunization. The immunization was also effective against metacyclic trypomastigote challenge. The immunogenicity of the killed T. cruzi suspension was retained after freeze-drying.", "contents": "Immunization against Trypanosoma cruzi using killed antigens and with saponin as adjuvant. The immunization of mice with killed epimastigotes or trypomastigotes with saponin SPL as adjuvant was challenged by inoculation of blood or metacyclic trypomastigotes of T. cruzi. Immunogenic preparations were obtained by freeze-thawing of formalin treatment. The protection was effective against homologous and heterologous challenge, and lasted up to 12 weeks after the last immunization. The immunization was also effective against metacyclic trypomastigote challenge. The immunogenicity of the killed T. cruzi suspension was retained after freeze-drying."}
{"id": "PMID:16475", "title": "Worms: transmission from animals to man.", "content": "It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog.", "contents": "Worms: transmission from animals to man. It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog."}
{"id": "PMID:16476", "title": "Sudden infant death syndrome (crib death).", "content": "Sudden infant death syndrome (SIDS) is diagnosed by the absence of lethal autopsy findings, or in a resuscitatable, \"near miss\" form with cyanosis, apnea, and bradycardia. The event is unexpected, although a minor respiratory infection is common, and occurs during sleep, between 1 and 6 months of age. There is growing evidence that the victims have had previous hypoxic episodes. Although suffocation is no longer considered a tenable explanation, other forms of airway obstruction are still postulated by many; the evidence, however, favors hypoxia as the common feature. A lethal arrhythmia had been proposed by several groups, based on inappropriate reflex activity, \"pathology\" of the conduction system, and the long QT syndrome, but the evidence is against arrhythmia as the primary event in most cases of SIDS. Based on the reversible \"near miss,\" apnea is likely as the primary event in SIDS. Several reflexes have the ability to produce apnea, in addition to the relatively common sleep apnea; the crucial aspect, rather, appears to be thefailure of the immature infant to resume respiration. The possibility exists that the infant, who did not have to breather for 9 months of fetal life, literally is not alarmed and aroused by the persistance of apnea. In human and animal studies, respiratory infections and sleep deprivation have been proved to increase the likelihood and duration of sleep apnea. If primary apnea continues for long (45 seconds or more), a dangerous positive feedback develops into hypoxic apnea. Hhis will persist until circulatory failure occurs, or until gasping occurs. The gasp is a highly effective mechanism at birth, but will occur too late for autoresuscitation after the anerobic capacity of fetal life dimineshes; we believe this capacity lasts for approximately 1 month, accounting for the hiatus of crib death, sparing the first month. The \"near-miss\" infant, after resuscitation, should be monitored at home, if practical, until 6 months of age. A simple cardiac monitor for bradycardia has definite advantage over an apnea monitor alone.", "contents": "Sudden infant death syndrome (crib death). Sudden infant death syndrome (SIDS) is diagnosed by the absence of lethal autopsy findings, or in a resuscitatable, \"near miss\" form with cyanosis, apnea, and bradycardia. The event is unexpected, although a minor respiratory infection is common, and occurs during sleep, between 1 and 6 months of age. There is growing evidence that the victims have had previous hypoxic episodes. Although suffocation is no longer considered a tenable explanation, other forms of airway obstruction are still postulated by many; the evidence, however, favors hypoxia as the common feature. A lethal arrhythmia had been proposed by several groups, based on inappropriate reflex activity, \"pathology\" of the conduction system, and the long QT syndrome, but the evidence is against arrhythmia as the primary event in most cases of SIDS. Based on the reversible \"near miss,\" apnea is likely as the primary event in SIDS. Several reflexes have the ability to produce apnea, in addition to the relatively common sleep apnea; the crucial aspect, rather, appears to be thefailure of the immature infant to resume respiration. The possibility exists that the infant, who did not have to breather for 9 months of fetal life, literally is not alarmed and aroused by the persistance of apnea. In human and animal studies, respiratory infections and sleep deprivation have been proved to increase the likelihood and duration of sleep apnea. If primary apnea continues for long (45 seconds or more), a dangerous positive feedback develops into hypoxic apnea. Hhis will persist until circulatory failure occurs, or until gasping occurs. The gasp is a highly effective mechanism at birth, but will occur too late for autoresuscitation after the anerobic capacity of fetal life dimineshes; we believe this capacity lasts for approximately 1 month, accounting for the hiatus of crib death, sparing the first month. The \"near-miss\" infant, after resuscitation, should be monitored at home, if practical, until 6 months of age. A simple cardiac monitor for bradycardia has definite advantage over an apnea monitor alone."}
{"id": "PMID:16478", "title": "Coronary arterial narrowing in Takayasu's aortitis.", "content": "A patient with Takayasu's aortitis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia is described. Takayasu's arteritis produces a panaortitis, with thickening of the adventitia predominating, and an inflammatory cell infiltrate involving the adventitia, outer media and vasa vasorum. Narrowing of the coronary arteries in this disease is due to extension into these arteries of the processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the aorta. The distal coronary arteries usually do not manifest arteritis and are normal in caliber. Angina pectoris may be the first symptom of the disease if the coronary arteries are the initial site of severe arterial narrowing. The coronary arterial bypass graft operation is effective therapy for treating coronary arterial narrowing due to Takayasu's arteritis.", "contents": "Coronary arterial narrowing in Takayasu's aortitis. A patient with Takayasu's aortitis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia is described. Takayasu's arteritis produces a panaortitis, with thickening of the adventitia predominating, and an inflammatory cell infiltrate involving the adventitia, outer media and vasa vasorum. Narrowing of the coronary arteries in this disease is due to extension into these arteries of the processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the aorta. The distal coronary arteries usually do not manifest arteritis and are normal in caliber. Angina pectoris may be the first symptom of the disease if the coronary arteries are the initial site of severe arterial narrowing. The coronary arterial bypass graft operation is effective therapy for treating coronary arterial narrowing due to Takayasu's arteritis."}
{"id": "PMID:16479", "title": "Derangements of myocardial metabolism preceding onset of ventricular fibrilliation after coronary occlusion.", "content": "To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.", "contents": "Derangements of myocardial metabolism preceding onset of ventricular fibrilliation after coronary occlusion. To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation."}
{"id": "PMID:16480", "title": "Effect of gallstone-dissolution therapy on human liver structure.", "content": "To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.", "contents": "Effect of gallstone-dissolution therapy on human liver structure. To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant."}
{"id": "PMID:16481", "title": "Studies on the pathogenesis of diet-induced dog gallstones.", "content": "Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.", "contents": "Studies on the pathogenesis of diet-induced dog gallstones. Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model."}
{"id": "PMID:16482", "title": "Absorption of short-chain fatty acids from the human ileum.", "content": "Acetate, propionate, and n-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0-100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparent K'm between 22 and 27 mM and a calculated Vmax between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell.", "contents": "Absorption of short-chain fatty acids from the human ileum. Acetate, propionate, and n-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0-100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparent K'm between 22 and 27 mM and a calculated Vmax between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell."}
{"id": "PMID:16483", "title": "Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences.", "content": "Intraluminal pH in the lower esophagus has been recorded during a 3-hr period following a ligh meal and a consecutive 12-hr nocturnal period in 20 patients with typical symptoms and radiological evidence of gastroesophageal reflux and in 10 patients without such signs of reflux. Evidence of acid reflux was obtained in 3 of the patients without reflux during the postcibal period but in only one during the 12-hr nocturnal period. In contrast all except one of the 20 patients who had evidence of reflux showed spells of high acidity both in the postcibal and nocturnal periods. There was no clear correlation between the frequency of paf high acidity in the nocturnal period. Those patients with endoscopic evidence of severe esophagitis showed a significantly longer duration of high esophageal acidity in the nocturnal period. We conclude that nocturnal exposure of the esophageal mucosa to acid is a major factor in the causation of reflux esophagitis.", "contents": "Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences. Intraluminal pH in the lower esophagus has been recorded during a 3-hr period following a ligh meal and a consecutive 12-hr nocturnal period in 20 patients with typical symptoms and radiological evidence of gastroesophageal reflux and in 10 patients without such signs of reflux. Evidence of acid reflux was obtained in 3 of the patients without reflux during the postcibal period but in only one during the 12-hr nocturnal period. In contrast all except one of the 20 patients who had evidence of reflux showed spells of high acidity both in the postcibal and nocturnal periods. There was no clear correlation between the frequency of paf high acidity in the nocturnal period. Those patients with endoscopic evidence of severe esophagitis showed a significantly longer duration of high esophageal acidity in the nocturnal period. We conclude that nocturnal exposure of the esophageal mucosa to acid is a major factor in the causation of reflux esophagitis."}
{"id": "PMID:16484", "title": "Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients.", "content": "The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients.", "contents": "Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients. The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients."}
{"id": "PMID:16488", "title": "Antimicrobial and other properties of a new stabilized alkaline glutaraldehyde disinfectant/sterilizer.", "content": "The properties of stabilized alkaline 2% glutaraldehyde solution (SGS) are discussed. SGS is discussed with regard to its chemistry, antimicrobial properties, organic soil resistance, toxicity, corrosivity and chemical stability. SGS retains the maximum antimicrobial activity of alkaline glutaraldehyde solutions and the chemical stability heretofore observed only with acidic glutaraldehyde solutions. These improvements, along with the inherent resistance of glutaraldehyde to neutralization by organic soil, allow SGS to be continuously used for 14 days in situations of high dilution, or 28 days in situations of low dilution.", "contents": "Antimicrobial and other properties of a new stabilized alkaline glutaraldehyde disinfectant/sterilizer. The properties of stabilized alkaline 2% glutaraldehyde solution (SGS) are discussed. SGS is discussed with regard to its chemistry, antimicrobial properties, organic soil resistance, toxicity, corrosivity and chemical stability. SGS retains the maximum antimicrobial activity of alkaline glutaraldehyde solutions and the chemical stability heretofore observed only with acidic glutaraldehyde solutions. These improvements, along with the inherent resistance of glutaraldehyde to neutralization by organic soil, allow SGS to be continuously used for 14 days in situations of high dilution, or 28 days in situations of low dilution."}
{"id": "PMID:16489", "title": "Propoxyphene: a review.", "content": "A critical analysis of information on propoxyphene that has been published since the drug's introduction is presented. Propoxyphene is discussed with regard to its chemistry, metabolism and pharmacokinetics, analgesic efficacy, analgesic efficacy of combination products, nonanalgesic uses, adverse effects, overdosage, and dependence and abuse. Both the hydrochloride and napsylate salts are covered. It is doubtful that propoxyphene hydrochloride 65 mg provides an analgesic effect equal to that of aspirin 650 mg. There is no conclusive evidence that combinations of propoxyphene with other analgesics are more effective than propoxyphene or other analgesics alone.", "contents": "Propoxyphene: a review. A critical analysis of information on propoxyphene that has been published since the drug's introduction is presented. Propoxyphene is discussed with regard to its chemistry, metabolism and pharmacokinetics, analgesic efficacy, analgesic efficacy of combination products, nonanalgesic uses, adverse effects, overdosage, and dependence and abuse. Both the hydrochloride and napsylate salts are covered. It is doubtful that propoxyphene hydrochloride 65 mg provides an analgesic effect equal to that of aspirin 650 mg. There is no conclusive evidence that combinations of propoxyphene with other analgesics are more effective than propoxyphene or other analgesics alone."}
{"id": "PMID:16490", "title": "Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay.", "content": "A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa.", "contents": "Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay. A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa."}
{"id": "PMID:16491", "title": "Bilateral atrial myxomas with multiple arterial aneurysms--a syndrome mimicking polyarteritis nodosa.", "content": "This patient, previously described as having polyarteritis nodosa with multiple aneurysms shown by angiography, was recently found to have bilateral atrial myxomas. The angiographic demonstration of multiple cerebral aneurysms has been described in a few cases of left atrial myxoma. This uncommon tumor is also accompanied by \"constitutional\" manifestations. Thus, a syndrome mimicking polyarteritis nodosa may be produced. Cardiac myxoma should be borne in mind in conditions with multifocal organic involvement, and they should be included in the list of conditions causing multiple arterial aneurysms.", "contents": "Bilateral atrial myxomas with multiple arterial aneurysms--a syndrome mimicking polyarteritis nodosa. This patient, previously described as having polyarteritis nodosa with multiple aneurysms shown by angiography, was recently found to have bilateral atrial myxomas. The angiographic demonstration of multiple cerebral aneurysms has been described in a few cases of left atrial myxoma. This uncommon tumor is also accompanied by \"constitutional\" manifestations. Thus, a syndrome mimicking polyarteritis nodosa may be produced. Cardiac myxoma should be borne in mind in conditions with multifocal organic involvement, and they should be included in the list of conditions causing multiple arterial aneurysms."}
{"id": "PMID:16492", "title": "Gonadotropin receptors in human corpora lutea of the menstrual cycle and pregnancy.", "content": "Binding of 125I-human choriogonadotropin (hCG) to homogenates of corpora lutea of the menstrual cycle and pregnancy was examined. While corpora lutea of the menstrual cycle bound 125I-hCG, most of the corpora lutea of pregnancy from six to 34 weeks' gestation bound little or none of the added 125 I-hCG. Further exploration into various possibilities for the above findings led to the conclusion that these corpora lutea either contain very few gonadotropin receptors or lack them altogether. The selected properties of gonadotropin receptors in corpora lutea of the cycle were studied. The apparent dissociation constant for binding was about the same (2.6 to 3.8 x 10-10M) in all but one corpus luteum. In this one sample the constant was three- to five-fold higher (1.3 x 10-9M). The binding was quite rapid and reversible, and it exhibited dependence on the amount of 125I-hCG, homogenate protein, pH of the incubation media, and duration of incubation. hCG and human lutropin (hLH') competed for 125I-hCG binding, but hCG subunits (alpha and beta), human follitropin, and ovine prolactin did not. Although hCG and hLH were parallel in inhibiting 125I-hCG binding, hLH was found to be relatively less effective. The studies with various enzymes revealed that gonadotropin receptors are protein in nature.", "contents": "Gonadotropin receptors in human corpora lutea of the menstrual cycle and pregnancy. Binding of 125I-human choriogonadotropin (hCG) to homogenates of corpora lutea of the menstrual cycle and pregnancy was examined. While corpora lutea of the menstrual cycle bound 125I-hCG, most of the corpora lutea of pregnancy from six to 34 weeks' gestation bound little or none of the added 125 I-hCG. Further exploration into various possibilities for the above findings led to the conclusion that these corpora lutea either contain very few gonadotropin receptors or lack them altogether. The selected properties of gonadotropin receptors in corpora lutea of the cycle were studied. The apparent dissociation constant for binding was about the same (2.6 to 3.8 x 10-10M) in all but one corpus luteum. In this one sample the constant was three- to five-fold higher (1.3 x 10-9M). The binding was quite rapid and reversible, and it exhibited dependence on the amount of 125I-hCG, homogenate protein, pH of the incubation media, and duration of incubation. hCG and human lutropin (hLH') competed for 125I-hCG binding, but hCG subunits (alpha and beta), human follitropin, and ovine prolactin did not. Although hCG and hLH were parallel in inhibiting 125I-hCG binding, hLH was found to be relatively less effective. The studies with various enzymes revealed that gonadotropin receptors are protein in nature."}
{"id": "PMID:16493", "title": "Effect of fenoterol (Th1165a) infusion on uterine and umbilical blood flow in pregnant sheep.", "content": "The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120  minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested  as the cause of this UtBF increase.", "contents": "Effect of fenoterol (Th1165a) infusion on uterine and umbilical blood flow in pregnant sheep. The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120  minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested  as the cause of this UtBF increase."}
{"id": "PMID:16494", "title": "The effect of umbilical vein occlusion on fetal oxygenation, cardiovascular parameters, and fetal electroencephalogram.", "content": "In 11 fetal sheep experiments, the blood pressure in the fetal aorta (FA) and in the umbilical vein (UV) was measured following umbilical vein occlusion (UVO), as was the fetal heart rate (FHR), pH, Pco2, and oxygen saturation (So2) in both fetal vessels, and umbilical blood flow (Qumb) of the common UV. The fetal electroencephalogram was recorded continuously throughout the experiment. The results (No. = 17) were grouped according to the response of FA So2 into moderate (So2greater than40 per cent, mean 49.8, S.D. 6.3, and severe So2less than40 per cent, mean 20.4, S.D. 9.2). After 8 to 10 seconds, the fetal blood pressure in FA increased. Umbilical vein blood pressure increased to 25 mm. Hg (S.D. 8) and 35 mm. Hg (S.D. 9) in the moderate and severe groups, respectively. As a result of the decreased perfusion pressure (FA-UV blood pressure) across the fetal side of the placenta, the Qumb fell from 147 ml. per kilogram per minute (S.D. 57) and 30 ml. per kilogram per minute (S.D. 55) to 84 ml. per kilogram per minute (S.D. 48) and 120 ml. per kilogram per minute (S.D.22), respectively. The fall in FA So2 was related to the decrease in Qumb: FA So2=37.6 x log Qumb - 22.8 (2alphaless than 0.001). There was a mild decrease in So2 from 70 to 55 per cent when Qumb fell from 250 to 120 ml. per kilogram per minute. Below 80 to 120ml. per kilogram per minute, the fall in FA So2 was almost linear. The So2 in the UV remained constant so that arteriovenous difference for oxygen (AV Do2) increased. Oxygen consumption decreased almost linearly when Qumb fell below 80 to 120 ml. per kilogram per minute. The fetal electroencephalogram showed no significant change in voltage and the faster activities. From these observations, it is concluded that a decrease in Qumb following UVO jeopardizes the fetus only if a critical Qumb of 80 to 120 ml. per kilogram per minute and fetal artery So2 of 50 to 60 per cent is achieved.", "contents": "The effect of umbilical vein occlusion on fetal oxygenation, cardiovascular parameters, and fetal electroencephalogram. In 11 fetal sheep experiments, the blood pressure in the fetal aorta (FA) and in the umbilical vein (UV) was measured following umbilical vein occlusion (UVO), as was the fetal heart rate (FHR), pH, Pco2, and oxygen saturation (So2) in both fetal vessels, and umbilical blood flow (Qumb) of the common UV. The fetal electroencephalogram was recorded continuously throughout the experiment. The results (No. = 17) were grouped according to the response of FA So2 into moderate (So2greater than40 per cent, mean 49.8, S.D. 6.3, and severe So2less than40 per cent, mean 20.4, S.D. 9.2). After 8 to 10 seconds, the fetal blood pressure in FA increased. Umbilical vein blood pressure increased to 25 mm. Hg (S.D. 8) and 35 mm. Hg (S.D. 9) in the moderate and severe groups, respectively. As a result of the decreased perfusion pressure (FA-UV blood pressure) across the fetal side of the placenta, the Qumb fell from 147 ml. per kilogram per minute (S.D. 57) and 30 ml. per kilogram per minute (S.D. 55) to 84 ml. per kilogram per minute (S.D. 48) and 120 ml. per kilogram per minute (S.D.22), respectively. The fall in FA So2 was related to the decrease in Qumb: FA So2=37.6 x log Qumb - 22.8 (2alphaless than 0.001). There was a mild decrease in So2 from 70 to 55 per cent when Qumb fell from 250 to 120 ml. per kilogram per minute. Below 80 to 120ml. per kilogram per minute, the fall in FA So2 was almost linear. The So2 in the UV remained constant so that arteriovenous difference for oxygen (AV Do2) increased. Oxygen consumption decreased almost linearly when Qumb fell below 80 to 120 ml. per kilogram per minute. The fetal electroencephalogram showed no significant change in voltage and the faster activities. From these observations, it is concluded that a decrease in Qumb following UVO jeopardizes the fetus only if a critical Qumb of 80 to 120 ml. per kilogram per minute and fetal artery So2 of 50 to 60 per cent is achieved."}
{"id": "PMID:16495", "title": "Cardiovascular effects of fever in the ewe and fetal lamb.", "content": "Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1 microng). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8 degrees C. higher than maternal temperature rose in parallel with the ewe's temperature. During the maternal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function.", "contents": "Cardiovascular effects of fever in the ewe and fetal lamb. Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1 microng). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8 degrees C. higher than maternal temperature rose in parallel with the ewe's temperature. During the maternal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function."}
{"id": "PMID:16497", "title": "Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli.", "content": "Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle.", "contents": "Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli. Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle."}
{"id": "PMID:16498", "title": "Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport.", "content": "Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length.", "contents": "Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport. Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length."}
{"id": "PMID:16499", "title": "Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog.", "content": "Studies were performed to evaluate the effects of the chronic administration of furosemide on hydrogen and electrolyte excretion in dogs on a normal electrolyte diet and in the absence of electrolyte or volume depletion. Control daily excretion in five dogs averaged 64 meq for Na, 51 meq for K, 66 meq for Cl, and 17 meq for net H. Furosemide, 40 mg, in the drinking water 3 times daily was given for 4 days. On day 1 Na excretion averaged 128 meq, but thereafter was not significantly different from control levels. Over 4 days cumulative net H excretion increased 63.6 meq and plasma HCO3 rose 6.6 meq/liter. The same dogs were restudied by the same protocol except that, to obviate electrolyte depletion, NaCl and KCl were administered daily in quantities sufficient to replace urinary losses. All dogs remained in positive Na, K, and Cl balance. Body weight, hematocrit, plasma albumin, creatinine, and plasma renin activity were unchanged, indicating the absence of electrolyte or volume depletion. Nonetheless, cumulative net H excretion increased 61.2 meq and plasma HCO3 increased 4.3 meq/liter. Two adrenalectomized dogs receiving steroid replacement showed similar changes in net H excretion and plasma HCO3. These experiments suggest that chronic furosemide administration may enhance H excretion and generate alkalosis even in the absence of volume or electrolyte depletion and without increased aldosterone secretion.", "contents": "Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog. Studies were performed to evaluate the effects of the chronic administration of furosemide on hydrogen and electrolyte excretion in dogs on a normal electrolyte diet and in the absence of electrolyte or volume depletion. Control daily excretion in five dogs averaged 64 meq for Na, 51 meq for K, 66 meq for Cl, and 17 meq for net H. Furosemide, 40 mg, in the drinking water 3 times daily was given for 4 days. On day 1 Na excretion averaged 128 meq, but thereafter was not significantly different from control levels. Over 4 days cumulative net H excretion increased 63.6 meq and plasma HCO3 rose 6.6 meq/liter. The same dogs were restudied by the same protocol except that, to obviate electrolyte depletion, NaCl and KCl were administered daily in quantities sufficient to replace urinary losses. All dogs remained in positive Na, K, and Cl balance. Body weight, hematocrit, plasma albumin, creatinine, and plasma renin activity were unchanged, indicating the absence of electrolyte or volume depletion. Nonetheless, cumulative net H excretion increased 61.2 meq and plasma HCO3 increased 4.3 meq/liter. Two adrenalectomized dogs receiving steroid replacement showed similar changes in net H excretion and plasma HCO3. These experiments suggest that chronic furosemide administration may enhance H excretion and generate alkalosis even in the absence of volume or electrolyte depletion and without increased aldosterone secretion."}
{"id": "PMID:16500", "title": "Effect of parathyroid hormone on urinary acidification.", "content": "The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption.", "contents": "Effect of parathyroid hormone on urinary acidification. The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption."}
{"id": "PMID:16501", "title": "Distribution of adenine nucleotides in the perfused rat heart.", "content": "A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate.", "contents": "Distribution of adenine nucleotides in the perfused rat heart. A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate."}
{"id": "PMID:16502", "title": "Computer simulation of energy metabolism in anoxic perfused rat heart.", "content": "We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed.", "contents": "Computer simulation of energy metabolism in anoxic perfused rat heart. We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed."}
{"id": "PMID:16503", "title": "Computer simulation of rat heart metabolism after adding glucose to the perfusate.", "content": "An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system.", "contents": "Computer simulation of rat heart metabolism after adding glucose to the perfusate. An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system."}
{"id": "PMID:16504", "title": "Relationship between gastric mucosal pH and site of peptic ulceration.", "content": "Measurements of mucosal pH of resected stomachs were carried out in gastric and duodenal ulcer patients. Low mucosal pH along the lesser curvature and relatively higher gastric pepsin levels were found. It is suggested that this lower pH affects gastric ulcer occurrence in the limited \"lesser curvature area\" where 63 per cent of the ulcers were situated. It is also suggested that increased pepsin activity present in gastric ulcer patients may be another factor affecting gastric ulcer formation by virtue of pepsins activated at higher pH. In duodenal ulcer patients, these factors are \"overshadowed\" by high acid-pepsin secretory activity of gastric juice.", "contents": "Relationship between gastric mucosal pH and site of peptic ulceration. Measurements of mucosal pH of resected stomachs were carried out in gastric and duodenal ulcer patients. Low mucosal pH along the lesser curvature and relatively higher gastric pepsin levels were found. It is suggested that this lower pH affects gastric ulcer occurrence in the limited \"lesser curvature area\" where 63 per cent of the ulcers were situated. It is also suggested that increased pepsin activity present in gastric ulcer patients may be another factor affecting gastric ulcer formation by virtue of pepsins activated at higher pH. In duodenal ulcer patients, these factors are \"overshadowed\" by high acid-pepsin secretory activity of gastric juice."}
{"id": "PMID:16506", "title": "The role of analgesics in respiratory depression: a rabbit model.", "content": "The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl.", "contents": "The role of analgesics in respiratory depression: a rabbit model. The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl."}
{"id": "PMID:16507", "title": "Formaldehyde formation as a metabolite of methoxyflurane.", "content": "The production of formaldehyde as a metabolite of enzymatic biotransformation of methoxyflurane was observed in vitro in hepatic microsomal preparations derived from Japanese monkeys, rabbits and Wistar strain rats. Production rates of formaldehyde were 0.80-2.50 n moles/mg protein/min in the induced group which was pretreated with phenobarbitone, and 0.15-0.68 n moles/mg protein/min in the non-induced group. This reaction needed the presence of NADPH and oxygen. Formaldehyde production was almost completely inhibited by addition of 25% CO. Further degradation of formaldehyde did not occur in microsomal suspension. No detectable species difference was observed among the animals used in this study. These results indicate that the biotransformation of methoxyflurane is preceded by interaction with cytochrome p-450 in hepatic microsomes in the presence of NADPH and oxygen.", "contents": "Formaldehyde formation as a metabolite of methoxyflurane. The production of formaldehyde as a metabolite of enzymatic biotransformation of methoxyflurane was observed in vitro in hepatic microsomal preparations derived from Japanese monkeys, rabbits and Wistar strain rats. Production rates of formaldehyde were 0.80-2.50 n moles/mg protein/min in the induced group which was pretreated with phenobarbitone, and 0.15-0.68 n moles/mg protein/min in the non-induced group. This reaction needed the presence of NADPH and oxygen. Formaldehyde production was almost completely inhibited by addition of 25% CO. Further degradation of formaldehyde did not occur in microsomal suspension. No detectable species difference was observed among the animals used in this study. These results indicate that the biotransformation of methoxyflurane is preceded by interaction with cytochrome p-450 in hepatic microsomes in the presence of NADPH and oxygen."}
{"id": "PMID:16508", "title": "[Anaesthesia with flunitrazepam (rohypnol) and fentanyl for geriatric patients (author's transl)].", "content": "Favorable clinic experiences with an anaesthetic involving rohypnol (flunitrazepam) and fentanyl led to an investigation of the haemodynamic effect of this procedure in a group of 9 geriatric patients, aged from 86 to 95 years. Anaesthesia was induced with 0.5 mg rohypnol and 0.1 to 0.2 mg fentanyl depending on the narcotic effect of rohypnol, intubation was performed under relaxation with suxamethonium and long term relaxation was achieved with pancuronium. The patients were normoventilated with nitrous oxide/oxygen. The individual values of the changes in cardiac output and total peripheral resistance showed a great variation. There was a significant correlation between the relative changes in mean arterial pressure and total peripheral resistance (r = 0.69, p less than 0.05) but no correlation between mean arterial pressure and cardiac output (r = 0.09). This indicates that the pronounced drop in arterial pressure which occurred in 4 patients can be explained by a decrease in total peripheral resistance. Careful dosage of the drugs, in particular of fentanyl, and knowledge of adequate measures to treat a decrease in blood pressure if it occurs, appears to be a prerequisite for the use of this type of anaesthesia in poor risk patients.", "contents": "[Anaesthesia with flunitrazepam (rohypnol) and fentanyl for geriatric patients (author's transl)]. Favorable clinic experiences with an anaesthetic involving rohypnol (flunitrazepam) and fentanyl led to an investigation of the haemodynamic effect of this procedure in a group of 9 geriatric patients, aged from 86 to 95 years. Anaesthesia was induced with 0.5 mg rohypnol and 0.1 to 0.2 mg fentanyl depending on the narcotic effect of rohypnol, intubation was performed under relaxation with suxamethonium and long term relaxation was achieved with pancuronium. The patients were normoventilated with nitrous oxide/oxygen. The individual values of the changes in cardiac output and total peripheral resistance showed a great variation. There was a significant correlation between the relative changes in mean arterial pressure and total peripheral resistance (r = 0.69, p less than 0.05) but no correlation between mean arterial pressure and cardiac output (r = 0.09). This indicates that the pronounced drop in arterial pressure which occurred in 4 patients can be explained by a decrease in total peripheral resistance. Careful dosage of the drugs, in particular of fentanyl, and knowledge of adequate measures to treat a decrease in blood pressure if it occurs, appears to be a prerequisite for the use of this type of anaesthesia in poor risk patients."}
{"id": "PMID:16509", "title": "[Paresis of the tympanic nerve--a rare complication of spinal anesthesia (author's transl)].", "content": "Acut impairment of hearing following spinal anaesthesia is described. The cause, treatment of and incidence rate of neurological complications of spinal anaesthesia are discussed.", "contents": "[Paresis of the tympanic nerve--a rare complication of spinal anesthesia (author's transl)]. Acut impairment of hearing following spinal anaesthesia is described. The cause, treatment of and incidence rate of neurological complications of spinal anaesthesia are discussed."}
{"id": "PMID:16512", "title": "Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit.", "content": "The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The  response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine.", "contents": "Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit. The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The  response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine."}
{"id": "PMID:16511", "title": "The splitting of sperm heads from tails in eight mammalian species and the measurement of their sizes.", "content": "Ejaculated spermatozoa from man, the Euopean wild boar and the bull, and spermatozoa from the cauda epididymes of the rabbit, rat, mouse, hamster and Guinea pig were treated with a sonic bath, a sonic probe, trypsin with and without prior treatment with a sulphhydryl reagent, pronase and alkalis. The fragments produced were counted and sized in an accurately calibrated Coulter Counter, Model ZB Industrial, before and after Zaponin treatment to lyse accompanying debris and the peripheral cytoplasm. Head and tail fractions were separated on sucrose gradients. Each species required different conditions for cleavage or fragmentation. Rabbit and bull spermatozoa were cleaved by the ultrasonic bath exactly into heads and tails, producing twice the number of particles with two peaks in the size distribution curves butith some 60% loss of total sperm volume which became the soluble fraction. The ultrasonic probe, and for the bull, pronase, produced the same cleavage but these more drastic treatments dissolved a considerable portion of the tail fraction. Rodent spermatozoa, especially the rat, were cleaved perfectly into heads and tails by mild trypsin treatment. All the nonrodent spermatozoa were resistent to trypsin cleavage, although prior treatment with a sulphhydryl reagent caused swelling and subsequent trypsin action caused digestion into miscellaneous pieces. Spermatozoa from the boar and from man could not be cleaved by any of the procedures. The sonic probe produced fragmentation with progressive dissolution of the tail fragments and a single peak in the size distribution curve corresponding to small stripped heads. The soluble fraction always constituted a large proportion of the original whole spermatozoa.", "contents": "The splitting of sperm heads from tails in eight mammalian species and the measurement of their sizes. Ejaculated spermatozoa from man, the Euopean wild boar and the bull, and spermatozoa from the cauda epididymes of the rabbit, rat, mouse, hamster and Guinea pig were treated with a sonic bath, a sonic probe, trypsin with and without prior treatment with a sulphhydryl reagent, pronase and alkalis. The fragments produced were counted and sized in an accurately calibrated Coulter Counter, Model ZB Industrial, before and after Zaponin treatment to lyse accompanying debris and the peripheral cytoplasm. Head and tail fractions were separated on sucrose gradients. Each species required different conditions for cleavage or fragmentation. Rabbit and bull spermatozoa were cleaved by the ultrasonic bath exactly into heads and tails, producing twice the number of particles with two peaks in the size distribution curves butith some 60% loss of total sperm volume which became the soluble fraction. The ultrasonic probe, and for the bull, pronase, produced the same cleavage but these more drastic treatments dissolved a considerable portion of the tail fraction. Rodent spermatozoa, especially the rat, were cleaved perfectly into heads and tails by mild trypsin treatment. All the nonrodent spermatozoa were resistent to trypsin cleavage, although prior treatment with a sulphhydryl reagent caused swelling and subsequent trypsin action caused digestion into miscellaneous pieces. Spermatozoa from the boar and from man could not be cleaved by any of the procedures. The sonic probe produced fragmentation with progressive dissolution of the tail fragments and a single peak in the size distribution curve corresponding to small stripped heads. The soluble fraction always constituted a large proportion of the original whole spermatozoa."}
{"id": "PMID:16518", "title": "[Membrane oxygenators in cardiac surgery: progress].", "content": "This study tries to define if the membrane oxygenators are available during cardiac surgery under E.C.C., and if their performance are superior to those of conventional oxygenators. Two series of research are done. In the first one, we compare performance of two membrane oxygenators: the Rh\u00f4ne-Poulenc heart-lung machine (10 cases) and the Travenol TMO Teflo machine (100 cases). The general impression is good: the two proposed systems seem to be perfectly well adapted to surgical utilization conditions, avoiding excessive ventilations and eventually allowing to keep on E.C.C. in postoperative. In the second part of this work, two series of patients are studied, one oeprated under membrane oxygenator (Teflo), the second under bubble oxygenator (Bentley Q 100). Comparative study shows small differences between the two groups. Only the post-operative enzymatic profile is clearly for the membrane oxygenator which also insure a waking and a postoperative recovery of highest quality. These first observations justify to keep on using of membrane oxygenators in cardiac surgery.", "contents": "[Membrane oxygenators in cardiac surgery: progress]. This study tries to define if the membrane oxygenators are available during cardiac surgery under E.C.C., and if their performance are superior to those of conventional oxygenators. Two series of research are done. In the first one, we compare performance of two membrane oxygenators: the Rh\u00f4ne-Poulenc heart-lung machine (10 cases) and the Travenol TMO Teflo machine (100 cases). The general impression is good: the two proposed systems seem to be perfectly well adapted to surgical utilization conditions, avoiding excessive ventilations and eventually allowing to keep on E.C.C. in postoperative. In the second part of this work, two series of patients are studied, one oeprated under membrane oxygenator (Teflo), the second under bubble oxygenator (Bentley Q 100). Comparative study shows small differences between the two groups. Only the post-operative enzymatic profile is clearly for the membrane oxygenator which also insure a waking and a postoperative recovery of highest quality. These first observations justify to keep on using of membrane oxygenators in cardiac surgery."}
{"id": "PMID:16519", "title": "[Methods of sampling and preservation of blood used during extracorporeal circulation].", "content": "The blood supply of Cardiac Surgery Centers set quantitative and qualitative problems to the Centers of blood dispatch. In this work, from a Lyonese experience on 4,000 E.C.C., authors try to define the best preservative solution, especially for the respiratory function of the red blood cell. The C.P.D. solution (citrate, phosphate, dextrose) answers to requirements in this field when the blood used is less than 48 hours old. In the meantime, it is not impossible that studies based on definite criteriums of evaluation and on severe comparisons allows to adapt new process from which some are described and criticized in this work.", "contents": "[Methods of sampling and preservation of blood used during extracorporeal circulation]. The blood supply of Cardiac Surgery Centers set quantitative and qualitative problems to the Centers of blood dispatch. In this work, from a Lyonese experience on 4,000 E.C.C., authors try to define the best preservative solution, especially for the respiratory function of the red blood cell. The C.P.D. solution (citrate, phosphate, dextrose) answers to requirements in this field when the blood used is less than 48 hours old. In the meantime, it is not impossible that studies based on definite criteriums of evaluation and on severe comparisons allows to adapt new process from which some are described and criticized in this work."}
{"id": "PMID:16520", "title": "[Value of using cell concentrates, preserved by freezing, during extracorporeal circulation].", "content": "The effectiveness of transfusions of frozen red cells has presently been clearly demonstrated. The authors present their technique of preparation of these cells and their experience of this material in 51 cases of ECC. The results observed plead in favour of the notion that frozen-defrosted blood, combines the advantages of washed blood, freed from all plasma and cellular contaminants of fresh blood with preservation of the oxyphoric power. Going beyond the realm of ECC, the authors think that cryopreservation of blood should be applied to the majority of indications for transfusions.", "contents": "[Value of using cell concentrates, preserved by freezing, during extracorporeal circulation]. The effectiveness of transfusions of frozen red cells has presently been clearly demonstrated. The authors present their technique of preparation of these cells and their experience of this material in 51 cases of ECC. The results observed plead in favour of the notion that frozen-defrosted blood, combines the advantages of washed blood, freed from all plasma and cellular contaminants of fresh blood with preservation of the oxyphoric power. Going beyond the realm of ECC, the authors think that cryopreservation of blood should be applied to the majority of indications for transfusions."}
{"id": "PMID:16521", "title": "[Technics, value and limitations of hemodilution in extracorporeal circulation].", "content": "Hemodilution during E.C.C. is into use for more than 15 years. Its interest is obvious (blood economy, beneficient action on viscosity, prevention of \"sludging\"), but opinions are different concerning the best level of hemodiultion. The authors defend the notion of a moderate dilution (hematocrit larger than or equal to 25 p. 100) required to maintain a high perfusion pressure. For atherosclerotic patients, they describe the hemodilution technics tried on more than 4,000 cases since 1964. The advantages of hemodilution concern on one hand the diminution or the disparition of drawbacks and complications due to the obtainment and to the administration of homologous blood and on the other hand the beneficient intrinsical effects of the blood dilution on the tissular perfusion. In convenients are those due to changes in the concentration of sodium, chlore and specially potassium which may be responsible of serious cardiac arrythmias. Because of increasing difficulties concerning the use of homologous blood (obtaining difficulties and complications relative to its use), the authors consider the utilization of autologous blood taken off before the operation on the patient and freezed.", "contents": "[Technics, value and limitations of hemodilution in extracorporeal circulation]. Hemodilution during E.C.C. is into use for more than 15 years. Its interest is obvious (blood economy, beneficient action on viscosity, prevention of \"sludging\"), but opinions are different concerning the best level of hemodiultion. The authors defend the notion of a moderate dilution (hematocrit larger than or equal to 25 p. 100) required to maintain a high perfusion pressure. For atherosclerotic patients, they describe the hemodilution technics tried on more than 4,000 cases since 1964. The advantages of hemodilution concern on one hand the diminution or the disparition of drawbacks and complications due to the obtainment and to the administration of homologous blood and on the other hand the beneficient intrinsical effects of the blood dilution on the tissular perfusion. In convenients are those due to changes in the concentration of sodium, chlore and specially potassium which may be responsible of serious cardiac arrythmias. Because of increasing difficulties concerning the use of homologous blood (obtaining difficulties and complications relative to its use), the authors consider the utilization of autologous blood taken off before the operation on the patient and freezed."}
{"id": "PMID:16522", "title": "[Biological aspects of extracorporeal circulation].", "content": "Two problems are looked at in this work. That of glucose which is administered in considerable quantities during ECC and that of the iso-enzymes. The administration of glucose has two aims: one being the mechanical nature i.e. as an agent which decreases the risks of platelet aggregation, the other bio-energetic. But, owing to the CRABTREEE effect, an excess of glucose blocks the biosynthesis of ATP and a non-metabolisable structural analogue which has mechanical properties identical with glucose, such as fucose or rhamnose could be supplied instead. As far as the iso-enzymes are concerned, the author after having looked at the general value from the standpoint of signs and symptoms, suggests the study of two of them, cardiac lactic-dehydrogenase and the MB fraction of creatine phosphokinase could enable the follow-up of the course and of the consequences of extra-corporeal circulation.", "contents": "[Biological aspects of extracorporeal circulation]. Two problems are looked at in this work. That of glucose which is administered in considerable quantities during ECC and that of the iso-enzymes. The administration of glucose has two aims: one being the mechanical nature i.e. as an agent which decreases the risks of platelet aggregation, the other bio-energetic. But, owing to the CRABTREEE effect, an excess of glucose blocks the biosynthesis of ATP and a non-metabolisable structural analogue which has mechanical properties identical with glucose, such as fucose or rhamnose could be supplied instead. As far as the iso-enzymes are concerned, the author after having looked at the general value from the standpoint of signs and symptoms, suggests the study of two of them, cardiac lactic-dehydrogenase and the MB fraction of creatine phosphokinase could enable the follow-up of the course and of the consequences of extra-corporeal circulation."}
{"id": "PMID:16523", "title": "[Sodium supply in operations under extracorporeal circulation in children].", "content": "In order to explain the edematous appearance found in infants after ECC associated with hyponatremia, the authors studied the supply of sodium per and post-operatively in 42 children aged from 11 days to 13 years undergoing correction of the cardiopathy under ECC. This study enables one to find that there is an inflation of sodium after intervention under ECC, which is even more important, the longer the duration of the ECC. It is not related to a failure in urinary excretion of Na+ and predominates in infants. It is related with the supply of sodium during transfusion and seems to be the cause of certain respiratory complications met with following ECC.", "contents": "[Sodium supply in operations under extracorporeal circulation in children]. In order to explain the edematous appearance found in infants after ECC associated with hyponatremia, the authors studied the supply of sodium per and post-operatively in 42 children aged from 11 days to 13 years undergoing correction of the cardiopathy under ECC. This study enables one to find that there is an inflation of sodium after intervention under ECC, which is even more important, the longer the duration of the ECC. It is not related to a failure in urinary excretion of Na+ and predominates in infants. It is related with the supply of sodium during transfusion and seems to be the cause of certain respiratory complications met with following ECC."}
{"id": "PMID:16525", "title": "[Hemodynamic parameters which should be watched during and immediately after extracorporeal circulation].", "content": "The author studies only the usual investigations required for watching E.C.C. during the operatory period and directly afterwards. During E.C.C., one must essentially oversee the flow (2,4l/m2 or 70 ml/kg), the arterial pressure (70 torrs) essential factor for myocardiac injection, the C.V.P., where excess is factor of cerebral oedema, the peripheric vascular resistances (P.V.R.) which inform on the level of vasomotoricity. Control of pulmonary capillary pressure (P.C.P.), which is under E.C.C. the reflection of the left ventricular pressure (L.V.P.) is also a capital element of this watching (any elevation of L.V.P. is factor of sub-endocardiac ischemia and of acute pulmonary edema). In post E.C.C., the same parameters will be watched. A cardiac output equal or inferior to 2 l/m2 involve an immediate treatment. The C.V.P. allows adaptation of blood quantity. Calcul of V.P.R. sets treatment of low cardiac output. C.P.C. control allows evaluation of left ventricular efficacity. These datas must be completed by calcul of subendocardiac viability by studying the arterial pressure curves which inform on oxygen supply and demand, and by the contractility index measure (aortic output speed and measure of systolic interval).", "contents": "[Hemodynamic parameters which should be watched during and immediately after extracorporeal circulation]. The author studies only the usual investigations required for watching E.C.C. during the operatory period and directly afterwards. During E.C.C., one must essentially oversee the flow (2,4l/m2 or 70 ml/kg), the arterial pressure (70 torrs) essential factor for myocardiac injection, the C.V.P., where excess is factor of cerebral oedema, the peripheric vascular resistances (P.V.R.) which inform on the level of vasomotoricity. Control of pulmonary capillary pressure (P.C.P.), which is under E.C.C. the reflection of the left ventricular pressure (L.V.P.) is also a capital element of this watching (any elevation of L.V.P. is factor of sub-endocardiac ischemia and of acute pulmonary edema). In post E.C.C., the same parameters will be watched. A cardiac output equal or inferior to 2 l/m2 involve an immediate treatment. The C.V.P. allows adaptation of blood quantity. Calcul of V.P.R. sets treatment of low cardiac output. C.P.C. control allows evaluation of left ventricular efficacity. These datas must be completed by calcul of subendocardiac viability by studying the arterial pressure curves which inform on oxygen supply and demand, and by the contractility index measure (aortic output speed and measure of systolic interval)."}
{"id": "PMID:16526", "title": "[Protection of the myocardium by hypothermia during extracorporeal circulation. Experimental and clinical study].", "content": "Hypothermic protection of myocardia during E.C.C. has been estimated on a 35 dogs experimental series and on a clinical series of 700 acquired cardiopathies of adult, including 400 valvular replacements and 300 aorto-coronary by-pass. Experimental results have been estimated by biochemic and morphologic controls done on myocardic samples took up by drillbiopsy. The biochemical study includes among others a dosing of the high-energy phosphorus compounds (P.C. and A.T.P.). Morphological study was done by optic and electronic microscopy. Results made clear the superiority of the hypothermic ischemia at 10 degrees C on the continued perfusion at 32 degrees C with fibrillative heart. An hypothermic protection method with successively cold perfusion of the coronary system and a heart immersion in a salted solution at 4 degrees C has been utilized during valvular and coronary surgery on human in 700 cases. The total mortality was of 5,8 p. 100. The rate of post-operative infarcts was 2,4 p. 100. Incidence of intra-ventricular conduction troubles has been 1,1 p. 100. There was no relation between mortality and morbidity of myocardic origin and the lasting of the ischemic clamp, which were of 21 mn up to 165 mn. The low incidence of complications of myocardic origin is due to the hypothermic protection of the myocardia.", "contents": "[Protection of the myocardium by hypothermia during extracorporeal circulation. Experimental and clinical study]. Hypothermic protection of myocardia during E.C.C. has been estimated on a 35 dogs experimental series and on a clinical series of 700 acquired cardiopathies of adult, including 400 valvular replacements and 300 aorto-coronary by-pass. Experimental results have been estimated by biochemic and morphologic controls done on myocardic samples took up by drillbiopsy. The biochemical study includes among others a dosing of the high-energy phosphorus compounds (P.C. and A.T.P.). Morphological study was done by optic and electronic microscopy. Results made clear the superiority of the hypothermic ischemia at 10 degrees C on the continued perfusion at 32 degrees C with fibrillative heart. An hypothermic protection method with successively cold perfusion of the coronary system and a heart immersion in a salted solution at 4 degrees C has been utilized during valvular and coronary surgery on human in 700 cases. The total mortality was of 5,8 p. 100. The rate of post-operative infarcts was 2,4 p. 100. Incidence of intra-ventricular conduction troubles has been 1,1 p. 100. There was no relation between mortality and morbidity of myocardic origin and the lasting of the ischemic clamp, which were of 21 mn up to 165 mn. The low incidence of complications of myocardic origin is due to the hypothermic protection of the myocardia."}
{"id": "PMID:16527", "title": "[Myocardial protection by coronary perfusion and specific problems of myocardial protection in combined valvular and coronary surgery].", "content": "The quality of the myocardial protection by bilateral coronary perfusion was studied in a consecutive series of 80 patients treated by isolated aortic replacements (47 cases) or multiple replacements (mitro-aortic, or mitro-aortic and tricuspid) 33 cases. Four low outputs (5 p. 100) were observed with only one death. Five post-operative necroses (6.25) were noted. The overall surgical mortality was 6.25 p. 100 (5 cases out of 80). There were two deaths in the series of the 47 single replacements and three deaths (9) in the series of multiple replacements. At the same time, the myocardial protection was studied in a consecutive series of 12 cases of valvular replacements combined with coronary shunts. In all of the cases, the shunt or shunts were carried out first, the myocardial protection was subsequently ensured by a coronary perfusion carried out by means of the shunts and directly through the coronary orifices. There were 2 deaths (16), 2 necroses (16) both responsible for deaths and no low output in the 10 survivors. Coronary perfusion very certainly ensures an excellent quality of myocardial protection if certain criteria are respected: hypothermia, moderate (28 degrees) bilateral perfusion with a mean perfusion pressure above 100 also ensuring a good flow through the sub-endocardial layer, which remains particularly sensitive to ischiemia. In cases of associated shunts, they must be carried out, first of all, in cases of tight senoses, over 60.", "contents": "[Myocardial protection by coronary perfusion and specific problems of myocardial protection in combined valvular and coronary surgery]. The quality of the myocardial protection by bilateral coronary perfusion was studied in a consecutive series of 80 patients treated by isolated aortic replacements (47 cases) or multiple replacements (mitro-aortic, or mitro-aortic and tricuspid) 33 cases. Four low outputs (5 p. 100) were observed with only one death. Five post-operative necroses (6.25) were noted. The overall surgical mortality was 6.25 p. 100 (5 cases out of 80). There were two deaths in the series of the 47 single replacements and three deaths (9) in the series of multiple replacements. At the same time, the myocardial protection was studied in a consecutive series of 12 cases of valvular replacements combined with coronary shunts. In all of the cases, the shunt or shunts were carried out first, the myocardial protection was subsequently ensured by a coronary perfusion carried out by means of the shunts and directly through the coronary orifices. There were 2 deaths (16), 2 necroses (16) both responsible for deaths and no low output in the 10 survivors. Coronary perfusion very certainly ensures an excellent quality of myocardial protection if certain criteria are respected: hypothermia, moderate (28 degrees) bilateral perfusion with a mean perfusion pressure above 100 also ensuring a good flow through the sub-endocardial layer, which remains particularly sensitive to ischiemia. In cases of associated shunts, they must be carried out, first of all, in cases of tight senoses, over 60."}
{"id": "PMID:16528", "title": "[Computer analysis of a method of myocardial protection used in a series of 547 operations under extracorporeal circulation in adults].", "content": "During 4 years (1970-1974), the numerous pre, per and post-operative datas collected for each adult operated under E.C.C. by the same surgeon, have been analysed on computer (547 cases). The myocardic protection method was unvariable: steady hypothermia of 30 degrees C, induced ventricular fibrillation, myocardic anoxia time less than 15 mn, strict out-bubbles of the left cavities. A direct perfusion of the coronary arteries has been used in case of aortotomy. Analysis of the early post-operative mortality causes and of the various post-operative myocardic complications did not reveal any baneful influence of this myocardic protection method. The average post-operative left auricular pressure, the most reliable test of the left ventricular dynamics, or its post-operative variations are independent of the ventricular fibrillation time, the perfusion time or the coronal output used.", "contents": "[Computer analysis of a method of myocardial protection used in a series of 547 operations under extracorporeal circulation in adults]. During 4 years (1970-1974), the numerous pre, per and post-operative datas collected for each adult operated under E.C.C. by the same surgeon, have been analysed on computer (547 cases). The myocardic protection method was unvariable: steady hypothermia of 30 degrees C, induced ventricular fibrillation, myocardic anoxia time less than 15 mn, strict out-bubbles of the left cavities. A direct perfusion of the coronary arteries has been used in case of aortotomy. Analysis of the early post-operative mortality causes and of the various post-operative myocardic complications did not reveal any baneful influence of this myocardic protection method. The average post-operative left auricular pressure, the most reliable test of the left ventricular dynamics, or its post-operative variations are independent of the ventricular fibrillation time, the perfusion time or the coronal output used."}
{"id": "PMID:16529", "title": "[Changes in myocardial tolerance to ischemia as a function of circulatory arrest mechanisms].", "content": "This study tries to specify the tolerance limit of heart to ischemia and has three parts. In the first one, the author considers the heart resistance in normothermy related to the circulatory arrest type, the anesthetic technique, existence or not or a ventricular fibrillation. Everybody is tody in agreement to admit that 35 to 45 minutes are the security limit of the cardiogenous circulatory stop. In the second part, conditions of cardiac tolerance to ischemia in hypothermy are foreseen. The security margin is here large, provided a nonagressive realization of the cooling. Lastly, the author reports the looseness of the biochimic, histochemic or histologic criteriums which permit an appreciation of the heart functional capacity, appreciation which still persist to be essentially clinical.", "contents": "[Changes in myocardial tolerance to ischemia as a function of circulatory arrest mechanisms]. This study tries to specify the tolerance limit of heart to ischemia and has three parts. In the first one, the author considers the heart resistance in normothermy related to the circulatory arrest type, the anesthetic technique, existence or not or a ventricular fibrillation. Everybody is tody in agreement to admit that 35 to 45 minutes are the security limit of the cardiogenous circulatory stop. In the second part, conditions of cardiac tolerance to ischemia in hypothermy are foreseen. The security margin is here large, provided a nonagressive realization of the cooling. Lastly, the author reports the looseness of the biochimic, histochemic or histologic criteriums which permit an appreciation of the heart functional capacity, appreciation which still persist to be essentially clinical."}
{"id": "PMID:16530", "title": "[Neuroplegia and extracorporeal circulation. Comparison between combinations of droperidol-phenoperidine and chlorprothixene-dextromoramide in cardiac surgery].", "content": "After a quick review of the physiopathology of extra-corporeal circulation, the value of the use of neuroplegic drugs in cardiac surgery is recalled by means of pharmacological arguments. The experimental differences existing between the combinations droperidol - phenoperidine and chlorportixene - dextromoramide, on the rate of flow and on the pressure of the perfusion, and on the esophago-rectal thermic gradients during E.C.C. is then demonstrated. Statistic calculation confirmed the superiority of chlorprotixene in the realm of tissue perfusion during E.C.C. under hypothermia.", "contents": "[Neuroplegia and extracorporeal circulation. Comparison between combinations of droperidol-phenoperidine and chlorprothixene-dextromoramide in cardiac surgery]. After a quick review of the physiopathology of extra-corporeal circulation, the value of the use of neuroplegic drugs in cardiac surgery is recalled by means of pharmacological arguments. The experimental differences existing between the combinations droperidol - phenoperidine and chlorportixene - dextromoramide, on the rate of flow and on the pressure of the perfusion, and on the esophago-rectal thermic gradients during E.C.C. is then demonstrated. Statistic calculation confirmed the superiority of chlorprotixene in the realm of tissue perfusion during E.C.C. under hypothermia."}
{"id": "PMID:16531", "title": "[Drug protection of the myocardium during cardiac surgery].", "content": "During aortic clamping, drug protection of the myocardium, far from supplanting hypothermia, complements it, particularly in the case of left ventricular hypertrophy. Ultramicroscopy and new techniques of histobiological exploration of the myocite have enabled one to distinguish the lessions provoked by anoxia from those induced by reperfusion. At present, drug protection, extended to energetic solutions and electrolytes, aim at preserving energy metabolism by stocking of the substrate and at avoiding interferences which precipitate exhaustion of the adenosine triphosphate and phosphocreatinine reserves. In order to do this, hemodilution in particular is limited in subjects with decompensated cardiopathy; choice of anesthetics is orientated towards neuroleptanalgesia or fluothane, and it is attempted to neutralize the adrenergic reaction by the use of beta-blocking substances. Furthermore, it is preferred to interrupt electrogenesis at the stage of polarization: depolarizing cardioplegic solutions rich in potassium and sodium are rejected and in preference membrane stabilizers are used (procaine, magnesium, tetrodoxine...) The ultramicroscopic analysis of the structural modifications leads to sparing of the integrity of the lysosomial membrane by corticoids and alkalines. The use of calcium is deferred, anti-calcium techniques are even proposed (washing poor in calcium, verapamil). Cellular edema is prevented and treated by solution (mannitol - sorbitol) whose osmolarity must be less than 300 M osm/l. A conditioning of the biochemical and physicial structures and of cardiac work is being more and more thought of which leads to the classification of beta stimulating substances as negative, and their indications must be seriously thought of and used with reserve.", "contents": "[Drug protection of the myocardium during cardiac surgery]. During aortic clamping, drug protection of the myocardium, far from supplanting hypothermia, complements it, particularly in the case of left ventricular hypertrophy. Ultramicroscopy and new techniques of histobiological exploration of the myocite have enabled one to distinguish the lessions provoked by anoxia from those induced by reperfusion. At present, drug protection, extended to energetic solutions and electrolytes, aim at preserving energy metabolism by stocking of the substrate and at avoiding interferences which precipitate exhaustion of the adenosine triphosphate and phosphocreatinine reserves. In order to do this, hemodilution in particular is limited in subjects with decompensated cardiopathy; choice of anesthetics is orientated towards neuroleptanalgesia or fluothane, and it is attempted to neutralize the adrenergic reaction by the use of beta-blocking substances. Furthermore, it is preferred to interrupt electrogenesis at the stage of polarization: depolarizing cardioplegic solutions rich in potassium and sodium are rejected and in preference membrane stabilizers are used (procaine, magnesium, tetrodoxine...) The ultramicroscopic analysis of the structural modifications leads to sparing of the integrity of the lysosomial membrane by corticoids and alkalines. The use of calcium is deferred, anti-calcium techniques are even proposed (washing poor in calcium, verapamil). Cellular edema is prevented and treated by solution (mannitol - sorbitol) whose osmolarity must be less than 300 M osm/l. A conditioning of the biochemical and physicial structures and of cardiac work is being more and more thought of which leads to the classification of beta stimulating substances as negative, and their indications must be seriously thought of and used with reserve."}
{"id": "PMID:16532", "title": "[Shivering during recovery after cardiac surgery under extracorporeal circulation. Inconveniences and methods of prevention].", "content": "Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering.", "contents": "[Shivering during recovery after cardiac surgery under extracorporeal circulation. Inconveniences and methods of prevention]. Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering."}
{"id": "PMID:16533", "title": "[Preventive treatment of acute renal failure in cardiac surgery].", "content": "The prevention of acute renal failure after cardiac surgery under extracorporeal circulation is possible during the pre-, per- and post-operative phases. During \"ECC\" the maintenance of \"correct\" renal perfusion is imperative, the same is also true of the post-operative period; the re-establishment of good hemodynamics is the best guarantee of maintenance of renal function. The prevention of infection is the second imperative.", "contents": "[Preventive treatment of acute renal failure in cardiac surgery]. The prevention of acute renal failure after cardiac surgery under extracorporeal circulation is possible during the pre-, per- and post-operative phases. During \"ECC\" the maintenance of \"correct\" renal perfusion is imperative, the same is also true of the post-operative period; the re-establishment of good hemodynamics is the best guarantee of maintenance of renal function. The prevention of infection is the second imperative."}
{"id": "PMID:16534", "title": "[Deep hypothermia on the infant: physiopathology and technics of ECC].", "content": "In 81 operations for correction of infants's cardiopathies, authors used, associated with E.C.C., a deep hypothermia allowing a circulatory arrest of an average duration of 52 minutes, according to the technics described by BARRAT-BOYES in 1971. From this experience, authors study the modifications brought to the organism by this hypothermia, and discuss the technical aspects in pre, per and post-operative periods. Mortality of this series is of 13,5 p. 100. It is in relation with the cardiopathy or it's correction, without anu possibility or directly charge the technique of hypothermia in its determinism. The early mortality includes a bilateral phrenic paralysis, an air embolism, three septic complications and two neurologic complications probably related to a poor thermic repartition. Advantages of this technique concern the possibility to operate in a bloodless field and a diminution of E.C.C. time.", "contents": "[Deep hypothermia on the infant: physiopathology and technics of ECC]. In 81 operations for correction of infants's cardiopathies, authors used, associated with E.C.C., a deep hypothermia allowing a circulatory arrest of an average duration of 52 minutes, according to the technics described by BARRAT-BOYES in 1971. From this experience, authors study the modifications brought to the organism by this hypothermia, and discuss the technical aspects in pre, per and post-operative periods. Mortality of this series is of 13,5 p. 100. It is in relation with the cardiopathy or it's correction, without anu possibility or directly charge the technique of hypothermia in its determinism. The early mortality includes a bilateral phrenic paralysis, an air embolism, three septic complications and two neurologic complications probably related to a poor thermic repartition. Advantages of this technique concern the possibility to operate in a bloodless field and a diminution of E.C.C. time."}
{"id": "PMID:16535", "title": "[Cerebral arterial embolism during extracorporeal circulation].", "content": "From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G.  and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen.", "contents": "[Cerebral arterial embolism during extracorporeal circulation]. From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G.  and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen."}
{"id": "PMID:16536", "title": "[Brachial diplegia--a post ECC neurological complication of a specific type].", "content": "Five cases of neurological disorders occurring after extra-corporeal circulation are presented owing to the singular nature of the clinical picture made up by the essential element of a progressive brachial diplegia, free from any sensory disorder. The topography of the lesion--single medullary lesion or bilateral encephalic--is discussed. An anatomic document enables the elimination of any m\u00e9dullary involvement in one of the cases, thus pointing to a bilateral central lesion. The physiopathological problems are looked at.", "contents": "[Brachial diplegia--a post ECC neurological complication of a specific type]. Five cases of neurological disorders occurring after extra-corporeal circulation are presented owing to the singular nature of the clinical picture made up by the essential element of a progressive brachial diplegia, free from any sensory disorder. The topography of the lesion--single medullary lesion or bilateral encephalic--is discussed. An anatomic document enables the elimination of any m\u00e9dullary involvement in one of the cases, thus pointing to a bilateral central lesion. The physiopathological problems are looked at."}
{"id": "PMID:16537", "title": "[Early neurological complications after cardiac surgery under ECC].", "content": "A non-trifling frequency (3,3 p. 100) of neurologic complications is observed after surgery under E.C.C. The part of some factors has been analysed and discussed, especially those played by the type of the system used, quality of the E.C.C., and the patients' conditions. Many problems are still unresolved. The actual gravity of observed troubles must bring a better harshness in preventive treatment, and to a more adjusted treatment when these troubles are noted.", "contents": "[Early neurological complications after cardiac surgery under ECC]. A non-trifling frequency (3,3 p. 100) of neurologic complications is observed after surgery under E.C.C. The part of some factors has been analysed and discussed, especially those played by the type of the system used, quality of the E.C.C., and the patients' conditions. Many problems are still unresolved. The actual gravity of observed troubles must bring a better harshness in preventive treatment, and to a more adjusted treatment when these troubles are noted."}
{"id": "PMID:16538", "title": "[Pulmonary complications after extracorporeal circulation. ECC lung syndrome].", "content": "Pulmonary complications after cardiac surgery under extracorporeal circulation remain frequent and sometimes grave, in spite of the great progress which has been made over the past 20 years in the methods of cardiorespiratory assistance. The authors analyse the clinical and radiological repercussions of perfusion on the lung, in 40 patients operated under ECC for coronary revascularisation. The simutaneous study of the arterial, and mixed venous blood gasses and of the alveolar gases, in 20 of these patients showed the constant occurrence of a shunt syndrome, without alveolar hypoventilation or disorders in peripheral circulatory flow. Ventilatory alcalosis, hypocapnia, hypoxemia and the rise in the alveolar arterial oxygen gradient is increased during the second post-operative day. Among the variables studied (duration of ECC, degree of hypothermia, duration of the intervention, duration of anesthesia, pleurotomy) only the latter intervened in a statistically significant manner in this study, in the increase in hypoxemia. 46 pulmonary biopsies carried out before and after ECC in 23 coronary patients were examined with the electron microscope. The initial alveolar involvement affects the septal microcirculation with signs of an increase in capillary permeability leading to an interstitial and epithelial destruction. The use of a membrane oxygenator prevents some of the alveolar lesions, as has been proved by the study of five pulmonary biopsies carried out in dogs submitted to ECC of long duration. Catherterization of the pulmonary artery carried out in 35 patients by means of a SWAN-GANZ catheter, before the intervention enabled supervision of the degree of importance and speed of the hemodynamic variations in the pulmonary circulation during the different phases of ECC (during the phase of ventricular fibrillation). The rise in the flow of left output can lead to the occurrence of negative pulmonary intravascular pressures which can be prejudicial for capillary trophicity. The syndrome of \"ECC lung\", a veritable \"induced post-agressive lung\" must be placed in the group of refractory hypoxemia of which it represents one of the most typical pictures.", "contents": "[Pulmonary complications after extracorporeal circulation. ECC lung syndrome]. Pulmonary complications after cardiac surgery under extracorporeal circulation remain frequent and sometimes grave, in spite of the great progress which has been made over the past 20 years in the methods of cardiorespiratory assistance. The authors analyse the clinical and radiological repercussions of perfusion on the lung, in 40 patients operated under ECC for coronary revascularisation. The simutaneous study of the arterial, and mixed venous blood gasses and of the alveolar gases, in 20 of these patients showed the constant occurrence of a shunt syndrome, without alveolar hypoventilation or disorders in peripheral circulatory flow. Ventilatory alcalosis, hypocapnia, hypoxemia and the rise in the alveolar arterial oxygen gradient is increased during the second post-operative day. Among the variables studied (duration of ECC, degree of hypothermia, duration of the intervention, duration of anesthesia, pleurotomy) only the latter intervened in a statistically significant manner in this study, in the increase in hypoxemia. 46 pulmonary biopsies carried out before and after ECC in 23 coronary patients were examined with the electron microscope. The initial alveolar involvement affects the septal microcirculation with signs of an increase in capillary permeability leading to an interstitial and epithelial destruction. The use of a membrane oxygenator prevents some of the alveolar lesions, as has been proved by the study of five pulmonary biopsies carried out in dogs submitted to ECC of long duration. Catherterization of the pulmonary artery carried out in 35 patients by means of a SWAN-GANZ catheter, before the intervention enabled supervision of the degree of importance and speed of the hemodynamic variations in the pulmonary circulation during the different phases of ECC (during the phase of ventricular fibrillation). The rise in the flow of left output can lead to the occurrence of negative pulmonary intravascular pressures which can be prejudicial for capillary trophicity. The syndrome of \"ECC lung\", a veritable \"induced post-agressive lung\" must be placed in the group of refractory hypoxemia of which it represents one of the most typical pictures."}
{"id": "PMID:16539", "title": "[Technics of anesthesia and hypothermia for the infant. Choice of replacement fluid for the circuit].", "content": "Sixty-five infants were submitted to complete repairment of a congenital cardiopathy under profound hypothermia and ECC. Description of the preparation of the young surgical patient, of the anesthesia, of the technique of ECC. The overall mortality was 35.5 p. 100. The hypothermia induced by ECC, does not introduce any supplementary risks as long as strict technical rules are respected.", "contents": "[Technics of anesthesia and hypothermia for the infant. Choice of replacement fluid for the circuit]. Sixty-five infants were submitted to complete repairment of a congenital cardiopathy under profound hypothermia and ECC. Description of the preparation of the young surgical patient, of the anesthesia, of the technique of ECC. The overall mortality was 35.5 p. 100. The hypothermia induced by ECC, does not introduce any supplementary risks as long as strict technical rules are respected."}
{"id": "PMID:16540", "title": "[Use of a membrane oxygenator in extracorporeal circulation in the child. Preliminary conclusions].", "content": "The comparison of two types of oxygenators, the bubble and membrane oxygenator, in cardiac surgery under ECC, in infants. The results were not subjected to a statistical study. However, it seems that the membrane oxygenator enables one to obtain a satisfactory hematosis in a simpler fashion (the addition of CO2 being avoided) than with the bubble oxygenator and leads to less hemolysis than the latter. In the cases of closed circuit ECC with recirculation, the use of the membrane oxygenator also gives greater security of manipulation of the blood mass.", "contents": "[Use of a membrane oxygenator in extracorporeal circulation in the child. Preliminary conclusions]. The comparison of two types of oxygenators, the bubble and membrane oxygenator, in cardiac surgery under ECC, in infants. The results were not subjected to a statistical study. However, it seems that the membrane oxygenator enables one to obtain a satisfactory hematosis in a simpler fashion (the addition of CO2 being avoided) than with the bubble oxygenator and leads to less hemolysis than the latter. In the cases of closed circuit ECC with recirculation, the use of the membrane oxygenator also gives greater security of manipulation of the blood mass."}
{"id": "PMID:16541", "title": "[Fluid mass distribution during extracorporeal circulation].", "content": "The author first recalls close relations existing in physiologic conditions between central venous pressure and blood mass. During E.C.C., this relation is out of truth through the action of venous correlations and of outout. Then studying distribution of blood mass in the different compartments, he notes that during E.C.C., the total organic fluid mass changes a little, but that the extracellular volume increases when the blood mass grows less. To these modifications shares in a seclusion of blood in the visceral compartment.", "contents": "[Fluid mass distribution during extracorporeal circulation]. The author first recalls close relations existing in physiologic conditions between central venous pressure and blood mass. During E.C.C., this relation is out of truth through the action of venous correlations and of outout. Then studying distribution of blood mass in the different compartments, he notes that during E.C.C., the total organic fluid mass changes a little, but that the extracellular volume increases when the blood mass grows less. To these modifications shares in a seclusion of blood in the visceral compartment."}
{"id": "PMID:16542", "title": "[Proteins and blood volume after cardiac surgery under ECC and hemodilution].", "content": "The variations in protein, bodyweight and circulating blood volume during operation are studied in 18 patients operated under ECC. The frequency of hypovolemia with hypoproteinemia and over hydration of the interstitial medium is confirmed. The prolongation of ECC beyond 120 minutes is accompanied by a considerable reduction in the plasma sector. The frequency of hypovolemia must render the use of diuretics prudent. The existence of hypoproteinemia and interstitial overload suggests the value of albumin perfusions.", "contents": "[Proteins and blood volume after cardiac surgery under ECC and hemodilution]. The variations in protein, bodyweight and circulating blood volume during operation are studied in 18 patients operated under ECC. The frequency of hypovolemia with hypoproteinemia and over hydration of the interstitial medium is confirmed. The prolongation of ECC beyond 120 minutes is accompanied by a considerable reduction in the plasma sector. The frequency of hypovolemia must render the use of diuretics prudent. The existence of hypoproteinemia and interstitial overload suggests the value of albumin perfusions."}
{"id": "PMID:16543", "title": "[Direct action of extracorporeal circulation on platelets and coagulation factors].", "content": "Concerning a study carried out in 250 patients, the authors confirm the classical notions concerning the fall in platelets, fibrinogenesis, factor II, XII AT3 and plasminogen during ECC. A more precise study of platelet levels shows important variations depending on the patients, whereas the length of time of ECC, the degree of importance of aspiration the first minutes of ECC, appear to be aggravating factors. There is no correlation between the type and the length of the circuit. Furthermore, from the morphological standpoint, thrombocytic changes are also noted. The same can be said of platelet function. In the last part of the work, the authors studied the causes of platelet consumption and their prevention. On the whole, and in practice, consumption of coagulation factors during ECC remains a little disturbing. It is, however, worth continuing to study their prevention.", "contents": "[Direct action of extracorporeal circulation on platelets and coagulation factors]. Concerning a study carried out in 250 patients, the authors confirm the classical notions concerning the fall in platelets, fibrinogenesis, factor II, XII AT3 and plasminogen during ECC. A more precise study of platelet levels shows important variations depending on the patients, whereas the length of time of ECC, the degree of importance of aspiration the first minutes of ECC, appear to be aggravating factors. There is no correlation between the type and the length of the circuit. Furthermore, from the morphological standpoint, thrombocytic changes are also noted. The same can be said of platelet function. In the last part of the work, the authors studied the causes of platelet consumption and their prevention. On the whole, and in practice, consumption of coagulation factors during ECC remains a little disturbing. It is, however, worth continuing to study their prevention."}
{"id": "PMID:16544", "title": "[Coagulation deficits and hemorrhagic consequences after cardiac surgery under ECC].", "content": "I--A statistical study of the results of tests of hemostasis was carried out in patients who had undergone major cardiac surgery with extra-corporeal circulation. There were two series of patients (1.504 and 547 operated) suffering mainly from congenital cardiopathies, valvulopathies or coronaritis. Bearing in mind the hematocrit and the total protein level, the following was studied before and after ECC and 24 hours after the intervation: the blood platelet level, fibrinogen, prothrombin and its cofactors, antithemophilic factors A and B, FDP amd fibrinolytic activity. The fall in platelet stickiness is specifically pointed out, and also the fall in the level of fibrin stablizing factor (factor XIII) which is met with after ECC, and which can explain the persistence of certain hemorrhagies. Furthermore, the fall in antithrombin III level then its rise can contribute to the \"heparine rebound\" occurring in certain cases after neutralization of heparinemia with protamine. II--The deficits in the quantitatively and qualitatively variable hemostatic factors do not necessarily lead to hemorrhage. Hemorrhage, due to biological causes, are met with in 5 to 6 p. 100 of the cases. Most of the time they are provoked by a residual hemorrhage or a \"heparine rebound\", deficits in coagulation factors, a DIVC syndrome, difficult to diagnose and to treat, or fibrinolysis, much more rarely nowadays, owing to the almost routine use of antiproteases. Sometimes, the check up of coagulation can be barely disturbed and local abnormalities in biological hemostasis which are still not well understood, are invoked in order to explain the hemorrhage.", "contents": "[Coagulation deficits and hemorrhagic consequences after cardiac surgery under ECC]. I--A statistical study of the results of tests of hemostasis was carried out in patients who had undergone major cardiac surgery with extra-corporeal circulation. There were two series of patients (1.504 and 547 operated) suffering mainly from congenital cardiopathies, valvulopathies or coronaritis. Bearing in mind the hematocrit and the total protein level, the following was studied before and after ECC and 24 hours after the intervation: the blood platelet level, fibrinogen, prothrombin and its cofactors, antithemophilic factors A and B, FDP amd fibrinolytic activity. The fall in platelet stickiness is specifically pointed out, and also the fall in the level of fibrin stablizing factor (factor XIII) which is met with after ECC, and which can explain the persistence of certain hemorrhagies. Furthermore, the fall in antithrombin III level then its rise can contribute to the \"heparine rebound\" occurring in certain cases after neutralization of heparinemia with protamine. II--The deficits in the quantitatively and qualitatively variable hemostatic factors do not necessarily lead to hemorrhage. Hemorrhage, due to biological causes, are met with in 5 to 6 p. 100 of the cases. Most of the time they are provoked by a residual hemorrhage or a \"heparine rebound\", deficits in coagulation factors, a DIVC syndrome, difficult to diagnose and to treat, or fibrinolysis, much more rarely nowadays, owing to the almost routine use of antiproteases. Sometimes, the check up of coagulation can be barely disturbed and local abnormalities in biological hemostasis which are still not well understood, are invoked in order to explain the hemorrhage."}
{"id": "PMID:16545", "title": "[Variations in hemostasis in the infant under deep hypothermia].", "content": "Effects on hemostasis of deep hypothermia on infant has been studied on 29 infants operated upon for a cardiopathy under deep hypothermia. Results of this study show a diminution of the coagulation factors rate, an augmentation of the fibrinolytic activity and an unforeseable variability of the residual heparin leading in all cases to a complement of the heparin neutralization by Protamine.", "contents": "[Variations in hemostasis in the infant under deep hypothermia]. Effects on hemostasis of deep hypothermia on infant has been studied on 29 infants operated upon for a cardiopathy under deep hypothermia. Results of this study show a diminution of the coagulation factors rate, an augmentation of the fibrinolytic activity and an unforeseable variability of the residual heparin leading in all cases to a complement of the heparin neutralization by Protamine."}
{"id": "PMID:16546", "title": "[Physiopathology of low cardiac outputs after ECC and their treatment].", "content": "Etiologic circumtances of low cardiac outputs are studied according as they concern a diminution of the precharge (hypovolemy of different reasons), an augmentation of the postcharge (by augmentation of aortic impedance or resistance to blood flow) or a cardiac deficiency. The latter can be of non-ischemic origin (effects of beta-blocking drugs, cardiac arrhytmias tamponade, deficience of myocardiac fiber, metabolic disease) or ischemic:--during E.C.C.: diminution of available oxygen (hypothermial), arterial pressure and output too low, clamping time or ventricular fibrillation too long;--after E.C.C.: insufficient surgical correction, coronary embolism lack of balance between apport and expense of oxygen. Therapeutics ways are discussed regarding the different etiologies. The central rule is that it is better to relieve an ischemic myocardia than lash it. But treatment of low cardiac outputs is most often an average solution which must be choose in regard to a well understood physiopathology.", "contents": "[Physiopathology of low cardiac outputs after ECC and their treatment]. Etiologic circumtances of low cardiac outputs are studied according as they concern a diminution of the precharge (hypovolemy of different reasons), an augmentation of the postcharge (by augmentation of aortic impedance or resistance to blood flow) or a cardiac deficiency. The latter can be of non-ischemic origin (effects of beta-blocking drugs, cardiac arrhytmias tamponade, deficience of myocardiac fiber, metabolic disease) or ischemic:--during E.C.C.: diminution of available oxygen (hypothermial), arterial pressure and output too low, clamping time or ventricular fibrillation too long;--after E.C.C.: insufficient surgical correction, coronary embolism lack of balance between apport and expense of oxygen. Therapeutics ways are discussed regarding the different etiologies. The central rule is that it is better to relieve an ischemic myocardia than lash it. But treatment of low cardiac outputs is most often an average solution which must be choose in regard to a well understood physiopathology."}
{"id": "PMID:16547", "title": "[Hemodynamic aspect of post ECC cardiac failures. Study of 193 cases].", "content": "The aim of this study is to define the hemodynamic characteristics of this \"clinical model\" of acute cardiac failure observed after cardiac surgery carried out under extra-corporeal circulation, which constitutes the essential cause of \"post-operative low cardiac output syndrome\". The 193 patients in this study make up a representative sample of patients operated, treated and studied according to a homogeneous methodology for a period of 1 year. The clinical analysis of the post-operative circulatory condition, after exclusion of non cardiogenic syndromes, led to grouping the cases into 5 classes of circulatory change of increasing severity, each corresponding to a specific \"therapeutic necessity\". The hemodynamic results (intra-vascular pressures, oxymetry, cardiac output by \"Cardio-Green\" dilution method) are given for each of the five classes, thus defining the \"hemodynamic profile\" and the statistical reliability of the main objective parameters. This gives proof of the therapeutic indications for the main therapeutic procedures actually known, for which we prevent the hemodynamic effects noted for each of them. Thus, three \"degrees of cardiac failure\" are found: less severe (classes I and II) call for simple metabolic equilibration and possibly diuretics: the systolic work is above 160 gm/m2. Decompensated circulatory failure (classes III and IV) corresponds to a more important reduction in systolic work (9) 15 gm/m2, i.e. between 20 et 40 p. 100 of the basal value), and call for sympatho-mimetic cardiotonic agents: isoprenaline and/or dopamine. Below this value, in spite of medical treatment, the hemodynamic situation can still be sometimes reversible under circulatory assistance (diastolic counter pressure by means of an aortic balloon). Confronted with the clinical picture, the hemodynamic study enables the quantification of the circulatory change, and specification of the cardiogenic part and thus especially helps the carrying out of the treatment.", "contents": "[Hemodynamic aspect of post ECC cardiac failures. Study of 193 cases]. The aim of this study is to define the hemodynamic characteristics of this \"clinical model\" of acute cardiac failure observed after cardiac surgery carried out under extra-corporeal circulation, which constitutes the essential cause of \"post-operative low cardiac output syndrome\". The 193 patients in this study make up a representative sample of patients operated, treated and studied according to a homogeneous methodology for a period of 1 year. The clinical analysis of the post-operative circulatory condition, after exclusion of non cardiogenic syndromes, led to grouping the cases into 5 classes of circulatory change of increasing severity, each corresponding to a specific \"therapeutic necessity\". The hemodynamic results (intra-vascular pressures, oxymetry, cardiac output by \"Cardio-Green\" dilution method) are given for each of the five classes, thus defining the \"hemodynamic profile\" and the statistical reliability of the main objective parameters. This gives proof of the therapeutic indications for the main therapeutic procedures actually known, for which we prevent the hemodynamic effects noted for each of them. Thus, three \"degrees of cardiac failure\" are found: less severe (classes I and II) call for simple metabolic equilibration and possibly diuretics: the systolic work is above 160 gm/m2. Decompensated circulatory failure (classes III and IV) corresponds to a more important reduction in systolic work (9) 15 gm/m2, i.e. between 20 et 40 p. 100 of the basal value), and call for sympatho-mimetic cardiotonic agents: isoprenaline and/or dopamine. Below this value, in spite of medical treatment, the hemodynamic situation can still be sometimes reversible under circulatory assistance (diastolic counter pressure by means of an aortic balloon). Confronted with the clinical picture, the hemodynamic study enables the quantification of the circulatory change, and specification of the cardiogenic part and thus especially helps the carrying out of the treatment."}
{"id": "PMID:16548", "title": "[Acute renal failure after cardiac surgery under extracorporeal circulation].", "content": "Acute renal failure (ARF) following cardiac surgery under extra-corporeal circulation is a grave but infrequent complication. Numerous physiopathological factors accounting for its origin are analyzed, those related to ECC and those of the immediate post-operative period. The course of these cares of ARF and the elements of the treatment are looked at.", "contents": "[Acute renal failure after cardiac surgery under extracorporeal circulation]. Acute renal failure (ARF) following cardiac surgery under extra-corporeal circulation is a grave but infrequent complication. Numerous physiopathological factors accounting for its origin are analyzed, those related to ECC and those of the immediate post-operative period. The course of these cares of ARF and the elements of the treatment are looked at."}
{"id": "PMID:16549", "title": "[Kidney failure after ectracorporeal circulation in cardiac surgery].", "content": "The renal function of 113 patients undergoing cardiac surgery under ECC was studied. In 32 p. 100 of the cases renal involvement was noted which was moderate in 18 p. 100 of the cases, severe in 10 p. 100 of the cases and anuric in 4 p. 100 of the cases. Valvular surgery was complicated once in every three cases by renal involvement, the repair of congenital malformations once out of every two cases, and coronary surgery in 17 p. 100 of the cases. The fall in renal perfusion represents the essential factor in this renal involvement, which should be avoided by the maintenace during ECC of a high output level and a satisfactory perfusion pressure and by the recovery of correct hemodynamics after the intervention.", "contents": "[Kidney failure after ectracorporeal circulation in cardiac surgery]. The renal function of 113 patients undergoing cardiac surgery under ECC was studied. In 32 p. 100 of the cases renal involvement was noted which was moderate in 18 p. 100 of the cases, severe in 10 p. 100 of the cases and anuric in 4 p. 100 of the cases. Valvular surgery was complicated once in every three cases by renal involvement, the repair of congenital malformations once out of every two cases, and coronary surgery in 17 p. 100 of the cases. The fall in renal perfusion represents the essential factor in this renal involvement, which should be avoided by the maintenace during ECC of a high output level and a satisfactory perfusion pressure and by the recovery of correct hemodynamics after the intervention."}
{"id": "PMID:16550", "title": "L(+) lactate dehydrogenase activity from the electric organ of Electrophorus electricus (L.).", "content": "Properties of L(+) lactate dehydrogenase (LDH) of Electrophorus electricus (L.) electric organ were studied, comparing the substrates pyruvate and lactate. Electric organ LDH is a soluble enzyme with a pH optimum of 7.4 for pyruvate and 9.0 for lactate. The apparent Km was lower for pyruvate (Km = 2.5 X 10(-4) M) than for lactate (Km = 1.5 X 10(-2) M). With lactate as a substrate at pH 7.4, malonate, oxalate and pyruvate inhibited competitively. For pyruvate as substrate at pH 9.0 malonate inhibited non-competitively and oxalate shiwed uncompetitive inhibition. The different effects of the carboxylic acids on LDH activity suggest different stereospecificities of the two enzyme-coenzyme complexes in the forward and reserve reactions. The reactions of electric organ LDH with substrates and inhibitors are consistent with electrophoretic analysis suggesting that the enzyme is of the M-type.", "contents": "L(+) lactate dehydrogenase activity from the electric organ of Electrophorus electricus (L.). Properties of L(+) lactate dehydrogenase (LDH) of Electrophorus electricus (L.) electric organ were studied, comparing the substrates pyruvate and lactate. Electric organ LDH is a soluble enzyme with a pH optimum of 7.4 for pyruvate and 9.0 for lactate. The apparent Km was lower for pyruvate (Km = 2.5 X 10(-4) M) than for lactate (Km = 1.5 X 10(-2) M). With lactate as a substrate at pH 7.4, malonate, oxalate and pyruvate inhibited competitively. For pyruvate as substrate at pH 9.0 malonate inhibited non-competitively and oxalate shiwed uncompetitive inhibition. The different effects of the carboxylic acids on LDH activity suggest different stereospecificities of the two enzyme-coenzyme complexes in the forward and reserve reactions. The reactions of electric organ LDH with substrates and inhibitors are consistent with electrophoretic analysis suggesting that the enzyme is of the M-type."}
{"id": "PMID:16554", "title": "Influence of reagent quality and reaction conditions on the determination of serum albumin by the bromcresol green dye-binding method.", "content": "In an age of reference methodologies and sophisticated quality control techniques it is surprising that so little attention is paid to the quality of the reagents that are used. This paper reports on an investigation of the bromcresol green dye-binding procedure for the estimation of serum albumin in which particular attention has been paid to changes in the reagent components that contribute to the performance of the method. It has been shown that detailed attention to the quality control of the reagents can improve the precision and interlaboratory comparison in the estimation of serum albumin.", "contents": "Influence of reagent quality and reaction conditions on the determination of serum albumin by the bromcresol green dye-binding method. In an age of reference methodologies and sophisticated quality control techniques it is surprising that so little attention is paid to the quality of the reagents that are used. This paper reports on an investigation of the bromcresol green dye-binding procedure for the estimation of serum albumin in which particular attention has been paid to changes in the reagent components that contribute to the performance of the method. It has been shown that detailed attention to the quality control of the reagents can improve the precision and interlaboratory comparison in the estimation of serum albumin."}
{"id": "PMID:16558", "title": "[Endocrine polyadenomatosis associated with prolactin pituitary adenoma and an intrathyroidal parathyroid adenoma].", "content": "A pituitary adenoma was removed transsphenoidally from a 20-yr-old woman with secondary amenorrhea, galactorrhea, and hyperprolactinemia. Light and electronic microscopy, immunocytology characterized a prolactin cell tumor. The patient also underwent three surgical explorations for hyperparathyroidism. Only after selective catheterization of thyroid veins with radioimmunoassay for parathormone, an intrathyroidal parathyroid adenoma was found. No other case of proven prolactin adenoma in Wermer's syndrome has been reported.", "contents": "[Endocrine polyadenomatosis associated with prolactin pituitary adenoma and an intrathyroidal parathyroid adenoma]. A pituitary adenoma was removed transsphenoidally from a 20-yr-old woman with secondary amenorrhea, galactorrhea, and hyperprolactinemia. Light and electronic microscopy, immunocytology characterized a prolactin cell tumor. The patient also underwent three surgical explorations for hyperparathyroidism. Only after selective catheterization of thyroid veins with radioimmunoassay for parathormone, an intrathyroidal parathyroid adenoma was found. No other case of proven prolactin adenoma in Wermer's syndrome has been reported."}
{"id": "PMID:16559", "title": "Renal function during and following obstruction.", "content": "The effects of urinary-tract obstruction on renal function have been clarified using modern physiologic techniques in animal models. These effects are obviously dependent on the severity and duration of obstruction, together with the presence or absence of extrarenal factors, particularly uremia, as exemplified by the differences in renal function between bilateral and unilateral obstruction. The beneficial effects on the unilateral postobstructive kidney of volume expansion (5) and the importance of azotemia in determining POD (20, 21) have possible clinical applications. Further experimental work is required to understand the mechanism responsible for the altered renal hemodynamics and decreased GFR, as well as the abnormalities in medullary function resulting from obstruction. Improvement in the management of this common clinical problem may then be forthcoming.", "contents": "Renal function during and following obstruction. The effects of urinary-tract obstruction on renal function have been clarified using modern physiologic techniques in animal models. These effects are obviously dependent on the severity and duration of obstruction, together with the presence or absence of extrarenal factors, particularly uremia, as exemplified by the differences in renal function between bilateral and unilateral obstruction. The beneficial effects on the unilateral postobstructive kidney of volume expansion (5) and the importance of azotemia in determining POD (20, 21) have possible clinical applications. Further experimental work is required to understand the mechanism responsible for the altered renal hemodynamics and decreased GFR, as well as the abnormalities in medullary function resulting from obstruction. Improvement in the management of this common clinical problem may then be forthcoming."}
{"id": "PMID:16560", "title": "Effect of anesthetic drugs on myocardial performance in man.", "content": "All potent CNS depressant drugs can depress cardiac function in man in a dose-dependent manner. The dose-effect curve is considerably flatter with several drugs (diethyl ether, cyclopropane, fluroxene, isoflurane, and ketamine), presumably from sympathetic nervous-system activation. Potent analgesics and tranquilizers appear to produce less depression, but have been incompletely studied. Neuromuscular blocking drugs and regional anesthesia produce minimal effects on the heart in healthy people. However, not as much is known about diseased man. For instance, nitrous oxide produces more depression in \"muscle\" function in IHD patients (43), while diazepam (28) and morphine (44) do not adversely affect pump function in this class of patients. Fluroxene (45) is more depressant in VHD patients, but nitrous oxide (46), morphine (30), fetanyl (46), and droperidol-fentanyl (46) seem to have equivalent effects to those seen in health patients. In any given patient, therefore, accurate prediction of the effect of any anesthetic drug on cardiac performance is not possible. Adequate monitoring and careful titration of drug dose offer the safest method of assuring a satisfactory response.", "contents": "Effect of anesthetic drugs on myocardial performance in man. All potent CNS depressant drugs can depress cardiac function in man in a dose-dependent manner. The dose-effect curve is considerably flatter with several drugs (diethyl ether, cyclopropane, fluroxene, isoflurane, and ketamine), presumably from sympathetic nervous-system activation. Potent analgesics and tranquilizers appear to produce less depression, but have been incompletely studied. Neuromuscular blocking drugs and regional anesthesia produce minimal effects on the heart in healthy people. However, not as much is known about diseased man. For instance, nitrous oxide produces more depression in \"muscle\" function in IHD patients (43), while diazepam (28) and morphine (44) do not adversely affect pump function in this class of patients. Fluroxene (45) is more depressant in VHD patients, but nitrous oxide (46), morphine (30), fetanyl (46), and droperidol-fentanyl (46) seem to have equivalent effects to those seen in health patients. In any given patient, therefore, accurate prediction of the effect of any anesthetic drug on cardiac performance is not possible. Adequate monitoring and careful titration of drug dose offer the safest method of assuring a satisfactory response."}
{"id": "PMID:16561", "title": "[Synthetic medium for the biosynthesis of gentamicin].", "content": "A synthetic medium for biosynthesis of gentamicin was developed. It includes maltose, gelatine, potassium phosphate, ammonium sulphate, cobalt chloride, sodium chloride, magnesium sulphate and zinc sulphate. The dynamics of the biochemical changes in the above medium was studied.", "contents": "[Synthetic medium for the biosynthesis of gentamicin]. A synthetic medium for biosynthesis of gentamicin was developed. It includes maltose, gelatine, potassium phosphate, ammonium sulphate, cobalt chloride, sodium chloride, magnesium sulphate and zinc sulphate. The dynamics of the biochemical changes in the above medium was studied."}
{"id": "PMID:16562", "title": "[Penicillin amidase from E. coli. Some physicochemical properties of the soluble enzyme].", "content": "Homogeneity of the enzyme was shown with the methods of gel filtration and disc electrophoresis. The molecular mass of penicillinamidase (PA) was determined. Sorption of PA by a carboxylic ion exchanger within a wide range of pH was studied. The values of pH in the ion exchanger phase under the conditions of the enzyme sorption were estimated. The ion exchange technique for determination of the isoelectric points of the proteins is described and the isoelectric point of PA is determined. It is proposed to use the method for estimation of close ionization constants of amphoteric an weak electrolites for interpretation of the bell-like pH dependence of kinetic and equilibrium parameters of the enzymatic reaction. The ionization constants of Michaelis complex of PA were evaluated. The activation energy of benzylpenicillin hydrolysis catalized by PA was determined.", "contents": "[Penicillin amidase from E. coli. Some physicochemical properties of the soluble enzyme]. Homogeneity of the enzyme was shown with the methods of gel filtration and disc electrophoresis. The molecular mass of penicillinamidase (PA) was determined. Sorption of PA by a carboxylic ion exchanger within a wide range of pH was studied. The values of pH in the ion exchanger phase under the conditions of the enzyme sorption were estimated. The ion exchange technique for determination of the isoelectric points of the proteins is described and the isoelectric point of PA is determined. It is proposed to use the method for estimation of close ionization constants of amphoteric an weak electrolites for interpretation of the bell-like pH dependence of kinetic and equilibrium parameters of the enzymatic reaction. The ionization constants of Michaelis complex of PA were evaluated. The activation energy of benzylpenicillin hydrolysis catalized by PA was determined."}
{"id": "PMID:16563", "title": "[Penicillin amidase from E. coli. Some physicochemical properties of the enzyme incorporated into polyacrylamide gel].", "content": "The physico-chemical properties of penicillinamidase (PA) immobilized in polyacrylamide gel (IPA) were investigated. It was shown that simple incorporation of PA into polyacrylamide gel was not effective because of gradual washing out of the enzyme. The use of a complex method for the immobilization (immobilization in the presence of a linking agent) resulted in higher stability of IPA, the choice of the optimal ratio of the reagents being of paramount importance. The mechanical strength of IPA was studied in model experiments.", "contents": "[Penicillin amidase from E. coli. Some physicochemical properties of the enzyme incorporated into polyacrylamide gel]. The physico-chemical properties of penicillinamidase (PA) immobilized in polyacrylamide gel (IPA) were investigated. It was shown that simple incorporation of PA into polyacrylamide gel was not effective because of gradual washing out of the enzyme. The use of a complex method for the immobilization (immobilization in the presence of a linking agent) resulted in higher stability of IPA, the choice of the optimal ratio of the reagents being of paramount importance. The mechanical strength of IPA was studied in model experiments."}
{"id": "PMID:16564", "title": "Penicillin resistance and penicillinase production in clinical isolates of Bacteroides melaninogenicus.", "content": "The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of Bacteroides melaninogenicus. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration >/=0.8 mug/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 mug of clindamycin per ml. All isolates with penicillin MIC values >/=0.8 mug/ml produced beta-lactamase using a slide method. A micro-iodometric assay was used to quantitate beta-lactamase production in six isolates. The beta-lactamase activity of B. melaninogenicus was comparable to that of a Staphylococcus aureus isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the beta-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy.", "contents": "Penicillin resistance and penicillinase production in clinical isolates of Bacteroides melaninogenicus. The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of Bacteroides melaninogenicus. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration >/=0.8 mug/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 mug of clindamycin per ml. All isolates with penicillin MIC values >/=0.8 mug/ml produced beta-lactamase using a slide method. A micro-iodometric assay was used to quantitate beta-lactamase production in six isolates. The beta-lactamase activity of B. melaninogenicus was comparable to that of a Staphylococcus aureus isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the beta-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy."}
{"id": "PMID:16571", "title": "Clinical and histological study of coal tar phototoxicity in humans.", "content": "Coal tars of different origin were compared with regard to their capacity to cause a phototoxic reaction in human skin. The photosensitizing potencies were found to differ. Tars that were partially refined had less activity than crude coal tar. An extract of tar, liquor carbonis detergens, was the least photosensitizing. The phototoxic reaction to coal tar was found to be a two-stage process, an immediate wheal associated with sharp burning, followed by a raised, red, infiltrated lesion peaking at 24 to 48 hours. The phototoxic reaction was completely prevented when arterial blood flow was cut off. The histological findings were prominently epidermal, with strong intracellular edema sometimes leading to microvesicles. It seems a possibility that assaying phototoxic potentiality may provide a convenient measure of therapeutic efficacy of materials derived from coal tar.", "contents": "Clinical and histological study of coal tar phototoxicity in humans. Coal tars of different origin were compared with regard to their capacity to cause a phototoxic reaction in human skin. The photosensitizing potencies were found to differ. Tars that were partially refined had less activity than crude coal tar. An extract of tar, liquor carbonis detergens, was the least photosensitizing. The phototoxic reaction to coal tar was found to be a two-stage process, an immediate wheal associated with sharp burning, followed by a raised, red, infiltrated lesion peaking at 24 to 48 hours. The phototoxic reaction was completely prevented when arterial blood flow was cut off. The histological findings were prominently epidermal, with strong intracellular edema sometimes leading to microvesicles. It seems a possibility that assaying phototoxic potentiality may provide a convenient measure of therapeutic efficacy of materials derived from coal tar."}
{"id": "PMID:16574", "title": "Comparison of the effects of alclofenac, flurbiprofen, and prednisolone on acute inflammatory response in the rat.", "content": "The fluid and cellular phases of the inflammatory response were measured using a technique employing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Fluribiprofen and prednisolone were equipotent and were capable of almost completely suppressing fluid and cellular responses, while alclofenac was less potent at nontoxic dose levels. Study of the patterns of cellular exudation by image analysing computer showed that alcofenac appears unique in that it produces a well-defined cell-free zone between the edge of the implanted cubes and a band of neutrophil polymorphs within the cubes.", "contents": "Comparison of the effects of alclofenac, flurbiprofen, and prednisolone on acute inflammatory response in the rat. The fluid and cellular phases of the inflammatory response were measured using a technique employing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Fluribiprofen and prednisolone were equipotent and were capable of almost completely suppressing fluid and cellular responses, while alclofenac was less potent at nontoxic dose levels. Study of the patterns of cellular exudation by image analysing computer showed that alcofenac appears unique in that it produces a well-defined cell-free zone between the edge of the implanted cubes and a band of neutrophil polymorphs within the cubes."}
{"id": "PMID:16576", "title": "Alpha-Isopropylmalate synthase from Alcaligenes eutrophus H 16 I. Purification and general properties.", "content": "alpha-Isopropylmalate (IPM) synthase, the first enzyme in the biosynthesis of L-leucine, was purified to a specific activity of 12 micronmole/min x mg protein from the valine-isoleucine double auxotrophic mutant A-81 of the hydrogen bacterium Alcaligenes eutrophus H16. The activity in crude extracts of derepressed cells was 0.106 micronmoles of isopropylmalate formed per min and per mg protein. Gel electrophoresis and regel electrophoresis of the isolated main band resulted in several distinct bands, which were not altered by the additions of substrate alpha-ketoisovalerate, feedback inhibitor leucine or other effectors. The isoelectric points of the enzyme protein was between 3.9 and 4.0. The molecular weight was 114 500 daltons and 100 000 respectively in the absence and presence of the feedback inhibitor leucine. The enzyme activity depended strongly on the pH, the optimum is at pH 8.2. The enzyme was could labile and exhibits temperature anomalies.", "contents": "Alpha-Isopropylmalate synthase from Alcaligenes eutrophus H 16 I. Purification and general properties. alpha-Isopropylmalate (IPM) synthase, the first enzyme in the biosynthesis of L-leucine, was purified to a specific activity of 12 micronmole/min x mg protein from the valine-isoleucine double auxotrophic mutant A-81 of the hydrogen bacterium Alcaligenes eutrophus H16. The activity in crude extracts of derepressed cells was 0.106 micronmoles of isopropylmalate formed per min and per mg protein. Gel electrophoresis and regel electrophoresis of the isolated main band resulted in several distinct bands, which were not altered by the additions of substrate alpha-ketoisovalerate, feedback inhibitor leucine or other effectors. The isoelectric points of the enzyme protein was between 3.9 and 4.0. The molecular weight was 114 500 daltons and 100 000 respectively in the absence and presence of the feedback inhibitor leucine. The enzyme activity depended strongly on the pH, the optimum is at pH 8.2. The enzyme was could labile and exhibits temperature anomalies."}
{"id": "PMID:16577", "title": "Adenosine-5'-phosphosulfate (APS) as sulfate donor for assimilatory sulfate reduction in Rhodospirillum rubrum.", "content": "Crude extracts of Rhodospirillum rubrum catalyzed the formation of acid-volatile radioactivity from (35S) sulfate, (35S) adenosine-5'-phosphosulfate, and (35S) 3'-phosphoadenosine-5'-phosphosulfate. An enzyme fraction similar to APS-sulfotransferases from plant sources was purified 228-fold from Rhodospirillum rubrum. It is suggested here that this enzyme is specific for adenosine-5'-phosphosulfate, because the purified enzyme fraction metabolized adenosine-5'-phosphosulfate; 3'-phosphoadenosine-5'-phosphosulfate, however, only at a rate of 1/10 of that with adenosine-5'-phosphosulfate. Further, the reaction with 3'-phosphoadenosine-5'-phosphosulfate was inhibited with 3'-phosphoadenosine-5'-phosphate whereas this nucleotide had no effect on the reaction with adenosine-5'-phosphosulfate. For this activity with adenosine-5'-phosphosulfate the name APS-sulfotransferase is suggested. This APS-sulfotransferase needs thiols for activity; good rates were obtained with either dithioerythritol or reduced glutathione; other thiols like cysteine, 2'-3'-dimercaptopropanol or mercaptoethanol are less effective. The electron donor methylviologen did not catalyze this reaction. The pH-optimum was about 9.0; the apparent Km for adenosine-5'phosphosulfate was determined to be 0.05 mM with this so far purified enzyme fraction. Enzyme activity was increased with K2SO4 and Na2SO4 and was inhibited by 5'-AMP. These properties are similar to assimilatory APS-sulfotransferases from spinach and Chlorella.", "contents": "Adenosine-5'-phosphosulfate (APS) as sulfate donor for assimilatory sulfate reduction in Rhodospirillum rubrum. Crude extracts of Rhodospirillum rubrum catalyzed the formation of acid-volatile radioactivity from (35S) sulfate, (35S) adenosine-5'-phosphosulfate, and (35S) 3'-phosphoadenosine-5'-phosphosulfate. An enzyme fraction similar to APS-sulfotransferases from plant sources was purified 228-fold from Rhodospirillum rubrum. It is suggested here that this enzyme is specific for adenosine-5'-phosphosulfate, because the purified enzyme fraction metabolized adenosine-5'-phosphosulfate; 3'-phosphoadenosine-5'-phosphosulfate, however, only at a rate of 1/10 of that with adenosine-5'-phosphosulfate. Further, the reaction with 3'-phosphoadenosine-5'-phosphosulfate was inhibited with 3'-phosphoadenosine-5'-phosphate whereas this nucleotide had no effect on the reaction with adenosine-5'-phosphosulfate. For this activity with adenosine-5'-phosphosulfate the name APS-sulfotransferase is suggested. This APS-sulfotransferase needs thiols for activity; good rates were obtained with either dithioerythritol or reduced glutathione; other thiols like cysteine, 2'-3'-dimercaptopropanol or mercaptoethanol are less effective. The electron donor methylviologen did not catalyze this reaction. The pH-optimum was about 9.0; the apparent Km for adenosine-5'phosphosulfate was determined to be 0.05 mM with this so far purified enzyme fraction. Enzyme activity was increased with K2SO4 and Na2SO4 and was inhibited by 5'-AMP. These properties are similar to assimilatory APS-sulfotransferases from spinach and Chlorella."}
{"id": "PMID:16578", "title": "Allohydroxy-D-proline dehydrogenase. An inducible membrane-bound enzyme in Pseudomonas aeruginosa PA01.", "content": "Growth of Pseudomonas aeruginosa PA01 on isomers of hydroxyproline induced the synthesis of an allohydroxy-D-proline dehydrogenase. The enzyme resembled the D-alanine dehydrogenase of this organism in its association with the particulate fraction and its linkage to oxygen through a cytochrome-containing respiratory chain, but differed from this and other bacterial D-amino acid dehydrogenases in its high substrate specificity and low Km.", "contents": "Allohydroxy-D-proline dehydrogenase. An inducible membrane-bound enzyme in Pseudomonas aeruginosa PA01. Growth of Pseudomonas aeruginosa PA01 on isomers of hydroxyproline induced the synthesis of an allohydroxy-D-proline dehydrogenase. The enzyme resembled the D-alanine dehydrogenase of this organism in its association with the particulate fraction and its linkage to oxygen through a cytochrome-containing respiratory chain, but differed from this and other bacterial D-amino acid dehydrogenases in its high substrate specificity and low Km."}
{"id": "PMID:16580", "title": "Neurophysiologic and pathologic aspects of acute and chronic pain.", "content": "Acute pain produced by disease or injury is the net effect of highly complex interactions of various neural systems and psychological factors. Through the interaction of the afferent systems and neocortical processes, the individual is provided perceptual information regarding location, magnitude, and spatial and temporal properties of the noxious stimulus that activates motivational tendencies toward escape or attack and permits analysis of multimodal information, past experience, and probability of outcome of different response strategies. In contrast, chronic pain is a malefic force that taxes the physical, emotional, and economic resources of the patient, his famiily, and society. Moreover, chronic pain is characterized by physiological affective and behavioral responses that are quite different than those of acute pain. The clinician must keep these differences in mind in order to provide patients with optimal relief of their pain.", "contents": "Neurophysiologic and pathologic aspects of acute and chronic pain. Acute pain produced by disease or injury is the net effect of highly complex interactions of various neural systems and psychological factors. Through the interaction of the afferent systems and neocortical processes, the individual is provided perceptual information regarding location, magnitude, and spatial and temporal properties of the noxious stimulus that activates motivational tendencies toward escape or attack and permits analysis of multimodal information, past experience, and probability of outcome of different response strategies. In contrast, chronic pain is a malefic force that taxes the physical, emotional, and economic resources of the patient, his famiily, and society. Moreover, chronic pain is characterized by physiological affective and behavioral responses that are quite different than those of acute pain. The clinician must keep these differences in mind in order to provide patients with optimal relief of their pain."}
{"id": "PMID:16581", "title": "[Ultrastructure of the parietal cells of the gastric mucosa in ulcer disease of the duodenum with a hyperacid syndrome (ultrastructurometric study)].", "content": "An electron-microscopy investigation and morphometric analysis were carried out in 30 specimens of bioptic material of the fundal part of the stomach in patients with duodenal ulcer with the hyperacid syndrome. At all levels of the Major gastric glands parietal cells with morphological signs of intensive secretory activity prevailed, which was one of the causes (apart from the increase in the mass of parietal cells) of considerable intensification of secretion of hydrochloric acid. It was suggested that a considerably increased (as compared with the norm) area of the surface of the crysts of mitochondria with simultaneous reduction of the coefficient of their fragmentation was the morphological substrate of a high functional activity of parietal cells of the gastric mucosa in the hyperacid syndrome.", "contents": "[Ultrastructure of the parietal cells of the gastric mucosa in ulcer disease of the duodenum with a hyperacid syndrome (ultrastructurometric study)]. An electron-microscopy investigation and morphometric analysis were carried out in 30 specimens of bioptic material of the fundal part of the stomach in patients with duodenal ulcer with the hyperacid syndrome. At all levels of the Major gastric glands parietal cells with morphological signs of intensive secretory activity prevailed, which was one of the causes (apart from the increase in the mass of parietal cells) of considerable intensification of secretion of hydrochloric acid. It was suggested that a considerably increased (as compared with the norm) area of the surface of the crysts of mitochondria with simultaneous reduction of the coefficient of their fragmentation was the morphological substrate of a high functional activity of parietal cells of the gastric mucosa in the hyperacid syndrome."}
{"id": "PMID:16582", "title": "Parkinson's disease.", "content": "The classical clinical picture of Parkinson's disease is all too frequently encountered in the elderly patient. The modern classification of causes of Parkinson's disease lists 'idiopathic', and 'post-encephalitic forms', the latter being uncommon in this community.", "contents": "Parkinson's disease. The classical clinical picture of Parkinson's disease is all too frequently encountered in the elderly patient. The modern classification of causes of Parkinson's disease lists 'idiopathic', and 'post-encephalitic forms', the latter being uncommon in this community."}
{"id": "PMID:16579", "title": "[Carbohydrate-dependent lipidogenesis. Review of the literature and experimental study].", "content": "The literature on glycide-induced lipidogenesis is reviewed. This is an important question also because of its relation to the pathogenesis of pathological conditions such as ketoacidosis, obesity and hypertriglyceridaemia. Doubt is expressed concerning the interpretation of some experimental procedures used in determining the extent of lipidogenesis in man. The questions raised are fully discussed. Their solution is sought via an experiment on the rat involving the comparison of tissue and plasma lipid metabolites values following infusion of a labelled glucose bolus. Little correlation was noted, low plasma levels being found with high tissue radioactivity. It is emphasized that it is very difficult to ideate a valid experimental approach in order to investigate the extent of lipidogenesis in man in vivo: in this respect, the long term risk arising from the use of tracers with a very long half-life (e.g. 14C) in man must be carefully valuated.", "contents": "[Carbohydrate-dependent lipidogenesis. Review of the literature and experimental study]. The literature on glycide-induced lipidogenesis is reviewed. This is an important question also because of its relation to the pathogenesis of pathological conditions such as ketoacidosis, obesity and hypertriglyceridaemia. Doubt is expressed concerning the interpretation of some experimental procedures used in determining the extent of lipidogenesis in man. The questions raised are fully discussed. Their solution is sought via an experiment on the rat involving the comparison of tissue and plasma lipid metabolites values following infusion of a labelled glucose bolus. Little correlation was noted, low plasma levels being found with high tissue radioactivity. It is emphasized that it is very difficult to ideate a valid experimental approach in order to investigate the extent of lipidogenesis in man in vivo: in this respect, the long term risk arising from the use of tracers with a very long half-life (e.g. 14C) in man must be carefully valuated."}
{"id": "PMID:16583", "title": "Survival test of submersible life support systems.", "content": "An experiment to validate predictions concerning submersible survivability was performed in December, 1975, by members of the Canadian Forces in the CF Submersible Lockout Vehicle SDL-1 in Halifax Harbour in water of 4 degrees C temperature at a depth of 40 ft. Data was collected relevant to the life support equipment to determine if it would operate for a simulated 6-h mission followed by a 24-h immobility period, at the end of which rescue was presumed to have occurred. Physiological data was collected from the submersible occupants in order to assess the degree of thermal stress experienced in this exercise. The experiment was terminated after a duration of approximately 25 h at 1 atm internal pressure due to exhaustion of two of the three on-board power supplies, causing the CO2 scrubbers to be inoperative and the CO2 content in the breathing gas to increase to toxic levels. Only two of the three submersible occupants experienced cold stress, one in the forward sphere and one in the aft sphere. At the end of 24 h, the core temperatures of both individuals had decreased by 0.5 degrees C and, during this time, skin temperatures, particularly of the extremities, had steadily and slowly decreased. Neither individual was hypothermic, but it was considered likely that after a 3-d exposure, at least two of the crew members would have had core temperatures of 35 degrees C or lower, assuming that CO2 poisoning had not occurred earlier.", "contents": "Survival test of submersible life support systems. An experiment to validate predictions concerning submersible survivability was performed in December, 1975, by members of the Canadian Forces in the CF Submersible Lockout Vehicle SDL-1 in Halifax Harbour in water of 4 degrees C temperature at a depth of 40 ft. Data was collected relevant to the life support equipment to determine if it would operate for a simulated 6-h mission followed by a 24-h immobility period, at the end of which rescue was presumed to have occurred. Physiological data was collected from the submersible occupants in order to assess the degree of thermal stress experienced in this exercise. The experiment was terminated after a duration of approximately 25 h at 1 atm internal pressure due to exhaustion of two of the three on-board power supplies, causing the CO2 scrubbers to be inoperative and the CO2 content in the breathing gas to increase to toxic levels. Only two of the three submersible occupants experienced cold stress, one in the forward sphere and one in the aft sphere. At the end of 24 h, the core temperatures of both individuals had decreased by 0.5 degrees C and, during this time, skin temperatures, particularly of the extremities, had steadily and slowly decreased. Neither individual was hypothermic, but it was considered likely that after a 3-d exposure, at least two of the crew members would have had core temperatures of 35 degrees C or lower, assuming that CO2 poisoning had not occurred earlier."}
{"id": "PMID:16584", "title": "Systematic desensitization of a phobia for flying with the use of suggestion.", "content": "This case study describes the successful treatment of a phobia for flying in an active-duty United States Marine helicopter crew chief by using systematic desensitization. Systematic desensitization is briefly described as a treatment technique which incorporates relaxation exercises paired with the visualization of anxiety-producing images--in this case, images associated with flying. The patient and the therapist constructed a hierarchy of 32 items which were then rank ordered from least to most anxiety producing with the first item being \"Ordering parts to repair a helicopter\" and the last item being \"A routine helicopter landing\". Treatment consisted of having the patient visualize the scenes from the list while achieving a state of deep relaxation. The patient was unique in that he possessed an extraordinary ability to experience olfactory, tactile, auditory, and kinesthetic cues as well as vivid visualizations when imagining the items. The patient moved to the next item on the list only after he could feel relaxed while visualizing the previously anxiety-arousing scene of the preceding item. After progressing through the entire list, the patient initiated an actual helicopter flight. The patient participated in a 6-month follow-up helicopter flight with the therapist and experienced an appropriate, manageable level of anxiety. The presentation concludes with a brief discussion concerning the protential usefulness of routinely incorporating relaxation exercises into flight training as a preventative approach to anxiety- and stress-related illness frequently found in aviators.", "contents": "Systematic desensitization of a phobia for flying with the use of suggestion. This case study describes the successful treatment of a phobia for flying in an active-duty United States Marine helicopter crew chief by using systematic desensitization. Systematic desensitization is briefly described as a treatment technique which incorporates relaxation exercises paired with the visualization of anxiety-producing images--in this case, images associated with flying. The patient and the therapist constructed a hierarchy of 32 items which were then rank ordered from least to most anxiety producing with the first item being \"Ordering parts to repair a helicopter\" and the last item being \"A routine helicopter landing\". Treatment consisted of having the patient visualize the scenes from the list while achieving a state of deep relaxation. The patient was unique in that he possessed an extraordinary ability to experience olfactory, tactile, auditory, and kinesthetic cues as well as vivid visualizations when imagining the items. The patient moved to the next item on the list only after he could feel relaxed while visualizing the previously anxiety-arousing scene of the preceding item. After progressing through the entire list, the patient initiated an actual helicopter flight. The patient participated in a 6-month follow-up helicopter flight with the therapist and experienced an appropriate, manageable level of anxiety. The presentation concludes with a brief discussion concerning the protential usefulness of routinely incorporating relaxation exercises into flight training as a preventative approach to anxiety- and stress-related illness frequently found in aviators."}
{"id": "PMID:16587", "title": "The intracellular pH and the buffer capacity of the heart.", "content": "The intracellular buffering (delta HCO3-/delta pH) in rats is lowest in skeletal muscle, intermediate in the diaphragm and highest in cardiac muscle. In the hypertrophic heart due to aortic constriction or to the Goldblatt mechanism the buffer value increases markedly during the first weeks, but returns to normal or even subnormal values during stable hypertrophy. There is an electrochemical disequilibrium for hydrogen ions caused by an active transport of ions across the cell membrane, which is possibly correlated to the myocardial activity.", "contents": "The intracellular pH and the buffer capacity of the heart. The intracellular buffering (delta HCO3-/delta pH) in rats is lowest in skeletal muscle, intermediate in the diaphragm and highest in cardiac muscle. In the hypertrophic heart due to aortic constriction or to the Goldblatt mechanism the buffer value increases markedly during the first weeks, but returns to normal or even subnormal values during stable hypertrophy. There is an electrochemical disequilibrium for hydrogen ions caused by an active transport of ions across the cell membrane, which is possibly correlated to the myocardial activity."}
{"id": "PMID:16618", "title": "Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies.", "content": "Lymphocytotoxic antibodies (LCTAB) were sought in sera of patients with rheumatic diseases and in family members. Patients with SLE and cutaneous necrotizing venulitis and family members of JRA patients had an increased frequency of LCTAB; JRA patients and family members of SLE patients did not. The only association between LCTAB and the HLA phenotype of persons with LCTAB was a decreased frequency of LCTAB in individuals with HLA-B27.", "contents": "Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies. Lymphocytotoxic antibodies (LCTAB) were sought in sera of patients with rheumatic diseases and in family members. Patients with SLE and cutaneous necrotizing venulitis and family members of JRA patients had an increased frequency of LCTAB; JRA patients and family members of SLE patients did not. The only association between LCTAB and the HLA phenotype of persons with LCTAB was a decreased frequency of LCTAB in individuals with HLA-B27."}
{"id": "PMID:16619", "title": "Determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma by gas liquid chromatography with an internal standard.", "content": "A method is developed for gas-chromatographic determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma, using methylclonazepam as internal standard. Following extraction of the benzodiazepines and their hydrolysis, the benzophenones are analyzed by gas-chromatography, with a glass column filled with 3% OV-225 on Gas Chrom Q and a 63Ni electron capture detector. The technique has a good selectivity. Its limit of sensitivity is about 0.5 ng/ml of plasma. It is suitable for investigations on pharmacokinetics and bioavailability as well as for monitoring the correlation between plasma level and therapeutic efficacy and toxicology.", "contents": "Determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma by gas liquid chromatography with an internal standard. A method is developed for gas-chromatographic determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma, using methylclonazepam as internal standard. Following extraction of the benzodiazepines and their hydrolysis, the benzophenones are analyzed by gas-chromatography, with a glass column filled with 3% OV-225 on Gas Chrom Q and a 63Ni electron capture detector. The technique has a good selectivity. Its limit of sensitivity is about 0.5 ng/ml of plasma. It is suitable for investigations on pharmacokinetics and bioavailability as well as for monitoring the correlation between plasma level and therapeutic efficacy and toxicology."}
{"id": "PMID:16620", "title": "[Studies on the reactability of chlordiazepoxide to its N-nitrosos derivative in physiological conditions (author's transl)].", "content": "It is shown that chlordiazepoxide readily reacts with sodium nitrite in an aqueous HCl solution as well as in human gastric juice to N-nitrosochlordiazepoxide with a high yield (up to 75%). For this reaction the pH optimum has been determined to be 1.4. After oral application of chlordiazepoxide alone or in combination with nitrite to rats, the drug as well as its N-nitroso derivative were recovered from serum and analysed by high-pressure liquid chromatography.", "contents": "[Studies on the reactability of chlordiazepoxide to its N-nitrosos derivative in physiological conditions (author's transl)]. It is shown that chlordiazepoxide readily reacts with sodium nitrite in an aqueous HCl solution as well as in human gastric juice to N-nitrosochlordiazepoxide with a high yield (up to 75%). For this reaction the pH optimum has been determined to be 1.4. After oral application of chlordiazepoxide alone or in combination with nitrite to rats, the drug as well as its N-nitroso derivative were recovered from serum and analysed by high-pressure liquid chromatography."}
{"id": "PMID:16621", "title": "Serum gonadotropins in the rat after prenatal damage to the testes by busulfan and their reaction to cryptorchidism, castration and administration of testosterone.", "content": "Adult male rats prenatally treated with 1,4-bis-(methanesulfonyloxy)-butane (busulfan), which damages the gonocytes, undergo cryptorchidization, castration or testosterone treatment and the FSH, LH and testosterone levels in serum are measured. Basal values of these hormones do not differ from those of controls. After cryptorchidization FSH levels rise but the LH levels do not. Following orchidectomy both hormone levels increase significantly. Application of testosterone in various doses increases FSH in normal animals but not in busulfan treated rats 24 h post infectionem. FSH and LH levels 7 days after administration do not differ from controls. According to the hypothesis that the FSH release depends on an inhibin from the testes, these experiments show evidence for inhibin being produced only in the Sertoli cells.", "contents": "Serum gonadotropins in the rat after prenatal damage to the testes by busulfan and their reaction to cryptorchidism, castration and administration of testosterone. Adult male rats prenatally treated with 1,4-bis-(methanesulfonyloxy)-butane (busulfan), which damages the gonocytes, undergo cryptorchidization, castration or testosterone treatment and the FSH, LH and testosterone levels in serum are measured. Basal values of these hormones do not differ from those of controls. After cryptorchidization FSH levels rise but the LH levels do not. Following orchidectomy both hormone levels increase significantly. Application of testosterone in various doses increases FSH in normal animals but not in busulfan treated rats 24 h post infectionem. FSH and LH levels 7 days after administration do not differ from controls. According to the hypothesis that the FSH release depends on an inhibin from the testes, these experiments show evidence for inhibin being produced only in the Sertoli cells."}
{"id": "PMID:16622", "title": "Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety.", "content": "A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in  comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships.", "contents": "Double-blind cross-over clinical comparison of two 2'-chloro benzodiazepines: 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (chlordesmethyldiazepam) versus 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) in neurotic anxiety. A group of 20 female neurotic inpatients has been treated with 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one-(chlordesmethyldiazepan)- 7-chloro-5(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam) according to a double-blind cross-over design. For each drug clinical evaluations were performed by means of Hamilton's rating scale for anxiety states and of Overall and Gorham's brief psychiatric rating scale, at the beginning, after the first week and at the end of the two-week period of treatment, in opposite sequence. A statistically greater efficacy of chlordesmethyldiazepam in  comparison to lorazepam was observed. Results are discussed with regard to benzodiazepine structure-activity relationships."}
{"id": "PMID:16623", "title": "[Psychic drugs: predicting therapeutic effects and doses by test models with normal subjects (author's transl)].", "content": "Pharmacopsychology is concerned with the effects of drugs on \"psychic\" processes. It is attempted to demonstrate approaches which meet the criteria of scientific methodology. These approaches are based upon observation of somatic and/or behavioral changes. The steps from \"naive\" observation to the generation of objective data consist mainly of strict control of the observational situation and of technical refinement of the observation methods. Two kinds of pharmacopsychological models in healthy volunteers are described: models of normal and models of abnormal behaviour. Their relevance for the prediction of therapeutic drug effects and dosage is discussed. Possible new approaches are demonstrated: a) utilization of feedback form clinical investigation to control the relevance of pharmacopsychological models and, b) the concept of symptomatic volunteers, who are shown to be more suitable models than non-selected subjects.", "contents": "[Psychic drugs: predicting therapeutic effects and doses by test models with normal subjects (author's transl)]. Pharmacopsychology is concerned with the effects of drugs on \"psychic\" processes. It is attempted to demonstrate approaches which meet the criteria of scientific methodology. These approaches are based upon observation of somatic and/or behavioral changes. The steps from \"naive\" observation to the generation of objective data consist mainly of strict control of the observational situation and of technical refinement of the observation methods. Two kinds of pharmacopsychological models in healthy volunteers are described: models of normal and models of abnormal behaviour. Their relevance for the prediction of therapeutic drug effects and dosage is discussed. Possible new approaches are demonstrated: a) utilization of feedback form clinical investigation to control the relevance of pharmacopsychological models and, b) the concept of symptomatic volunteers, who are shown to be more suitable models than non-selected subjects."}
{"id": "PMID:16624", "title": "Destruction of endogenous low density lipoprotein in incubated intima.", "content": "The effect of incubation on the content of endogenous intact plasma lipoprotein (LP) has been examined in minced samples of normal intima and lesions from 38 patients. Both the electrophoretically mobile and the immobilized LP fractions decreased on incubation, and the rate of destruction was proportional to LP concentration (r=0.832, p less than 0.001). Mincing the intima with EDTA before incubation increased the rate of destruction about 4-fold in fibrous lesions but not in lesions containing numerous fat-filled cells. The destruction of LP was highly dependent on pH; the rate was highest below pH  5.5 and destruction was almost completely inhibited above pH 6.4. In standard cathepsin assays haemoglobin substrate was hydrolysed at a rate comparable to the rate of destruction of LP. The results suggest that LP may be degraded by a lysosomal cathepsin in intima.", "contents": "Destruction of endogenous low density lipoprotein in incubated intima. The effect of incubation on the content of endogenous intact plasma lipoprotein (LP) has been examined in minced samples of normal intima and lesions from 38 patients. Both the electrophoretically mobile and the immobilized LP fractions decreased on incubation, and the rate of destruction was proportional to LP concentration (r=0.832, p less than 0.001). Mincing the intima with EDTA before incubation increased the rate of destruction about 4-fold in fibrous lesions but not in lesions containing numerous fat-filled cells. The destruction of LP was highly dependent on pH; the rate was highest below pH  5.5 and destruction was almost completely inhibited above pH 6.4. In standard cathepsin assays haemoglobin substrate was hydrolysed at a rate comparable to the rate of destruction of LP. The results suggest that LP may be degraded by a lysosomal cathepsin in intima."}
{"id": "PMID:16625", "title": "Effect of prostaglandins E1 and F1alpha on the activities of cholesteryl ester synthetase and cholesteryl ester hydrolases of pigeon aorta in vitro.", "content": "The in vitro effects of prostaglandins E1 and F1alpha on the activity of cholesteryl ester synthetase and cholesteryl ester hydrolase activities of the pigeon aorta were examined. It was found that prostaglandin E1 markedly inhibited the cholesteryl ester hydrolase activity in the supernatant fraction and slightly  inhibited the cholesteryl ester synthetase activity. Prostaglandin F1alpha, however, modestly stimulated the cholesteryl ester hydrolase activity both in the microsomal and in the supernatant fraction of the aorta. These observations strongly warrant further studies on the role of prostaglandins in atherogenesis.", "contents": "Effect of prostaglandins E1 and F1alpha on the activities of cholesteryl ester synthetase and cholesteryl ester hydrolases of pigeon aorta in vitro. The in vitro effects of prostaglandins E1 and F1alpha on the activity of cholesteryl ester synthetase and cholesteryl ester hydrolase activities of the pigeon aorta were examined. It was found that prostaglandin E1 markedly inhibited the cholesteryl ester hydrolase activity in the supernatant fraction and slightly  inhibited the cholesteryl ester synthetase activity. Prostaglandin F1alpha, however, modestly stimulated the cholesteryl ester hydrolase activity both in the microsomal and in the supernatant fraction of the aorta. These observations strongly warrant further studies on the role of prostaglandins in atherogenesis."}
{"id": "PMID:16632", "title": "Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.", "content": "1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man.", "contents": "Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man. 1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man."}
{"id": "PMID:16633", "title": "Measurement of thioridazine in blood and urine.", "content": "1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non-specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine-plus-sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0-7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half-life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding.", "contents": "Measurement of thioridazine in blood and urine. 1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non-specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine-plus-sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0-7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half-life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding."}
{"id": "PMID:16634", "title": "The metabolism, distribution and elimination of chlorphentermine in man.", "content": "1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed.", "contents": "The metabolism, distribution and elimination of chlorphentermine in man. 1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed."}
{"id": "PMID:16635", "title": "A repeated dose comparison of dichloralphenazone, flunitrazepam and amylobarbitone sodium on some aspects of sleep and early morning behaviour in normal subjects.", "content": "1 Seven normal subjects were given three different hypnotics (flunitrazepam 1 mg, amylobarbitone sodium 100 mg and dichloralphenazone 1300 mg) for four consecutive nights each. 2 All three substances improved subjective assessment of the ease of getting to sleep. Flunitrazepam was rated as better than eithr dichloralphenazone or amylobarbitone sodium in this respect. 3 The perceived quality of induced sleep was not altered by any of the preparations. 4 There was a disturbance of the subjective ratings of getting to sleep following cessation of treatment with dichloralphenazone, giving tentative support to the existence of a 'rebound' effect. 5 Dichloralphenazone produced an impairment in psychomotor performance as measured on a complex reaction time test following four nights medication with the drug.", "contents": "A repeated dose comparison of dichloralphenazone, flunitrazepam and amylobarbitone sodium on some aspects of sleep and early morning behaviour in normal subjects. 1 Seven normal subjects were given three different hypnotics (flunitrazepam 1 mg, amylobarbitone sodium 100 mg and dichloralphenazone 1300 mg) for four consecutive nights each. 2 All three substances improved subjective assessment of the ease of getting to sleep. Flunitrazepam was rated as better than eithr dichloralphenazone or amylobarbitone sodium in this respect. 3 The perceived quality of induced sleep was not altered by any of the preparations. 4 There was a disturbance of the subjective ratings of getting to sleep following cessation of treatment with dichloralphenazone, giving tentative support to the existence of a 'rebound' effect. 5 Dichloralphenazone produced an impairment in psychomotor performance as measured on a complex reaction time test following four nights medication with the drug."}
{"id": "PMID:16637", "title": "Localized scleroderma-like lesions after bone marrow transplantation in man. A chronic graft versus host reaction.", "content": "Localized scleroderma-like skin lesions which developed in two children, from 8 to 10 months after successful bone marrow transplantation for aplastic anaemia, showed histopathological features resembling those of scleroderma. This finding, like the animal models described in the literature, provides additional support for the auto-immune nature of scleroderma.", "contents": "Localized scleroderma-like lesions after bone marrow transplantation in man. A chronic graft versus host reaction. Localized scleroderma-like skin lesions which developed in two children, from 8 to 10 months after successful bone marrow transplantation for aplastic anaemia, showed histopathological features resembling those of scleroderma. This finding, like the animal models described in the literature, provides additional support for the auto-immune nature of scleroderma."}
{"id": "PMID:16638", "title": "Proton nuclear magnetic resonance study of the effect of pH on tRNA structure.", "content": "The low-field 220-MHz proton nuclear magnetic resonance (NMR) spectra of four tRNA molecules, Escherichia coli tRNAPhe, tRNA1Val, and tRNAfMet1, and yeast tRNAPhe, at neutral and mildly acidic pH are compared. We find a net increase in the number of resonances contributing to the -9.9-ppm peak (downfield from sodium 4,4-dimethyl-4-silapentanesulfonate) in three of these tRNAs at pH 6, while tRNAfMet1 does not clearly exhibit this behavior. The increase in intensity at this resonance position is half-completed at pH 6.2 in the case of yeast tRNAPhe. An alteration at the 5'-phosphate terminus is not involved, since removal of the terminal phosphate does not affect the gain in intensity at -9.9 ppm. Based on a survey of the tertiary interactions in the four molecules, assuming that they possess tertiary structures like that of yeast tRNAPhe at neutral pH, we tentatively attribute this altered resonance in E. coli and yeast tRNAPhe to the protonation of the N3 of the adenine residue at position 9 which results in the stabilization of the tertiary triple A23-U12-A9. This intepretation is supported by model studies on the lowfield proton NMR spectrum of AN oligomers at acid pH, which reveal an exchanging proton resonance at -9.4 ppm if the chain length N greater than or equal to 6.", "contents": "Proton nuclear magnetic resonance study of the effect of pH on tRNA structure. The low-field 220-MHz proton nuclear magnetic resonance (NMR) spectra of four tRNA molecules, Escherichia coli tRNAPhe, tRNA1Val, and tRNAfMet1, and yeast tRNAPhe, at neutral and mildly acidic pH are compared. We find a net increase in the number of resonances contributing to the -9.9-ppm peak (downfield from sodium 4,4-dimethyl-4-silapentanesulfonate) in three of these tRNAs at pH 6, while tRNAfMet1 does not clearly exhibit this behavior. The increase in intensity at this resonance position is half-completed at pH 6.2 in the case of yeast tRNAPhe. An alteration at the 5'-phosphate terminus is not involved, since removal of the terminal phosphate does not affect the gain in intensity at -9.9 ppm. Based on a survey of the tertiary interactions in the four molecules, assuming that they possess tertiary structures like that of yeast tRNAPhe at neutral pH, we tentatively attribute this altered resonance in E. coli and yeast tRNAPhe to the protonation of the N3 of the adenine residue at position 9 which results in the stabilization of the tertiary triple A23-U12-A9. This intepretation is supported by model studies on the lowfield proton NMR spectrum of AN oligomers at acid pH, which reveal an exchanging proton resonance at -9.4 ppm if the chain length N greater than or equal to 6."}
{"id": "PMID:16639", "title": "Sodium-dependent methyl 1-thio-beta-D-galactopyranoside transport in membrane vesicles isolated from Salmonella typhimurium.", "content": "Membrane vesicles isolated from Salmonella typhimurium G-30 grown in the presence of melibiose catalyze methyl 1-thio-beta-D-galactopyranoside (TMG) transport in the presence of sodium or lithium, as shown initially with intact cells by Stock and Roseman (Stock, J., and Roseman, S. (1971), Biochem. Biophys. Res. Commun. 44, 132). TMG-dependent sodium uptake is also observed, but only when a potassium diffusion potential (interior negative) is induced across the vesicle membrane. Cation-dependent TMG accumulation varies with the electrochemical gradient of protons generated as a result of D-lactate oxidation, and the vesicles catalyze D-lactate-dependent sodium efflux in a manner which is consistent with the operation of a proton-sodium exchange mechanism. Although the stoichiometry between sodium and TMG appears to be 1:1 when transport is induced by a potassium diffusion potential, evidence is presented which indicates that the relationship may exceed unity under certain conditions. The results are explained in terms of a model in which TMG-sodium (lithium) symport is driven by an electrochemical gradient of protons which functions to maintain a low intravesicular sodium or lithium concentration through proton--sodium (lithium) antiport.", "contents": "Sodium-dependent methyl 1-thio-beta-D-galactopyranoside transport in membrane vesicles isolated from Salmonella typhimurium. Membrane vesicles isolated from Salmonella typhimurium G-30 grown in the presence of melibiose catalyze methyl 1-thio-beta-D-galactopyranoside (TMG) transport in the presence of sodium or lithium, as shown initially with intact cells by Stock and Roseman (Stock, J., and Roseman, S. (1971), Biochem. Biophys. Res. Commun. 44, 132). TMG-dependent sodium uptake is also observed, but only when a potassium diffusion potential (interior negative) is induced across the vesicle membrane. Cation-dependent TMG accumulation varies with the electrochemical gradient of protons generated as a result of D-lactate oxidation, and the vesicles catalyze D-lactate-dependent sodium efflux in a manner which is consistent with the operation of a proton-sodium exchange mechanism. Although the stoichiometry between sodium and TMG appears to be 1:1 when transport is induced by a potassium diffusion potential, evidence is presented which indicates that the relationship may exceed unity under certain conditions. The results are explained in terms of a model in which TMG-sodium (lithium) symport is driven by an electrochemical gradient of protons which functions to maintain a low intravesicular sodium or lithium concentration through proton--sodium (lithium) antiport."}
{"id": "PMID:16640", "title": "Determination of the rate-limiting steps and chemical mechanism of fructokinase by isotope exchange, isotope partitioning, and pH studies.", "content": "Isotope exchange studies show that beef liver fructokinase has a random kinetic mechanism in which release of fructose from the enzyme is slower than that catalytic reaction. The stickiness of fructose in the presence of MgATP is confirmed by isotope partition studies, which show it to be released 0.53 times as fast as V1/Et in the presence, and 80--130 times as fast in the absence of MgATP. Fructose-1-P release from it binary complex is not at all rate limiting in the forward direction since no exchange of MgADP back into MgATP could be observed during the forward reaction. Failure to find any isotope effect by the equilibrium perturbation method with [1-18O]fructose (upper limit, 1.003, shows that P--O bond cleavage or formation is not rate limiting. The pH profiles for the forward reaction show a group (probably carboxyl with pK 5.7-6.0 and deltaHion = 0) that must be ionized and a group (perhaps lysine, with pK 9--10, and deltaHion 5-9 kcal/mol) which must be protonated for activity. The profile for the back reaction shows only a group with pK 5.5--6 that must be protonated for activity. A chemical mechanism is proposed in which a carboxyl group on the enzyme accepts a proton from the 1-hydroxyl of fructose during the forward reaction and donates it back during the reverse reaction.", "contents": "Determination of the rate-limiting steps and chemical mechanism of fructokinase by isotope exchange, isotope partitioning, and pH studies. Isotope exchange studies show that beef liver fructokinase has a random kinetic mechanism in which release of fructose from the enzyme is slower than that catalytic reaction. The stickiness of fructose in the presence of MgATP is confirmed by isotope partition studies, which show it to be released 0.53 times as fast as V1/Et in the presence, and 80--130 times as fast in the absence of MgATP. Fructose-1-P release from it binary complex is not at all rate limiting in the forward direction since no exchange of MgADP back into MgATP could be observed during the forward reaction. Failure to find any isotope effect by the equilibrium perturbation method with [1-18O]fructose (upper limit, 1.003, shows that P--O bond cleavage or formation is not rate limiting. The pH profiles for the forward reaction show a group (probably carboxyl with pK 5.7-6.0 and deltaHion = 0) that must be ionized and a group (perhaps lysine, with pK 9--10, and deltaHion 5-9 kcal/mol) which must be protonated for activity. The profile for the back reaction shows only a group with pK 5.5--6 that must be protonated for activity. A chemical mechanism is proposed in which a carboxyl group on the enzyme accepts a proton from the 1-hydroxyl of fructose during the forward reaction and donates it back during the reverse reaction."}
{"id": "PMID:16641", "title": "Carbon-13 nuclear magnetic resonance probe of active-site ionizations in human carbonic anhydrase B.", "content": "Human carbonic anhydrase B (HCAB), prepared by a new affinity chromatography procedure, was carboxymethylated exclusively at NT of its active-site histidine-200 using 90% [1-13C]bromoacetate. The 13C nuclear magnetic resonance signal of the covalently attached carboxylate was easily detected over the natural abundance background due to the other carbonyl and carboxyl carbons of this 29 000 molecular weight zinc metalloenzyme. Its chemical shift proved very sensitive to the presence of inhibitors in the active site and to variations in pH. Two perturbing groups with pKa values of 6.0 and 9.2 were assigned to the modified histidine-200 itself and the zinc-bound water ligand, respectively, making use of 13C NMR titration data on Nr- and Nr-carboxymethyl-L-histidine model compounds. The results rule out histidine-200 as the critical  group whose ionization controls the catalytic activity. They also strongly suggest an interaction of the carboxylate of the carboxymethyl group with either the zinc or its water ligand around pH 8, possibly explaining the basis for the major differences between HCAB and CmHCAB.", "contents": "Carbon-13 nuclear magnetic resonance probe of active-site ionizations in human carbonic anhydrase B. Human carbonic anhydrase B (HCAB), prepared by a new affinity chromatography procedure, was carboxymethylated exclusively at NT of its active-site histidine-200 using 90% [1-13C]bromoacetate. The 13C nuclear magnetic resonance signal of the covalently attached carboxylate was easily detected over the natural abundance background due to the other carbonyl and carboxyl carbons of this 29 000 molecular weight zinc metalloenzyme. Its chemical shift proved very sensitive to the presence of inhibitors in the active site and to variations in pH. Two perturbing groups with pKa values of 6.0 and 9.2 were assigned to the modified histidine-200 itself and the zinc-bound water ligand, respectively, making use of 13C NMR titration data on Nr- and Nr-carboxymethyl-L-histidine model compounds. The results rule out histidine-200 as the critical  group whose ionization controls the catalytic activity. They also strongly suggest an interaction of the carboxylate of the carboxymethyl group with either the zinc or its water ligand around pH 8, possibly explaining the basis for the major differences between HCAB and CmHCAB."}
{"id": "PMID:16642", "title": "Comparison of solubility properties of alpha-paramyosin, beta-paramyosin and acid-extracted paramyosin.", "content": "The solubility properties of paramyosin in the zones of pH and ionic strength in which aggregation occurs were initially studied using preparations isolated by a method originally described by Bailey (Bailey, K. (1956), Pubbl. Stn. Zool. Napoli 29, 26). Other preparations yielding apparently different protein components have been described by Hodge (Hodge, A.J. (1952), Proc. Natl. Acad. Sci., U.S.A. 38, 850) using acid conditions, and Stafford and Yphantis (Stafford, W.F., AND Yphantis, D. (1972), Biochem. Biophys. Res. Commun. 49, 848) have identified alpha-, beta-, and gamma-paramyosin using various times and temperatures of extraction with or without ethylenediaminetetraacetic acid. We have found that acid-extracted paramyosin is very similar if not identical to alpha-paramyosin, but that both acid and alpha forms differ considerably from beta- and gamma-paramyosin. Beta-Paramyosin precipitates abruptly from solution in narrow zone of pH below neutrality, and increases in ionic strength shift the zone of precipitation toward lower pH values. In contrast, both acid and alpha-paramyosin show gradual aggregation with changing pH at lowerionic strength (less than 0.3) but sharp transitions similar to beta-paramyosin at higher ionic strength (greater than 0.3). Transitions were also found at lower pH (ca. 4.0) which were not mirror images of transitions at higher pH (ca. 7.0). Viscosity measurements show that acid extracted paramyosin is close in behavior to a native extract obtained by extraction in mild, nondenaturing media containing mixed antibiotics. Each of these extracts differed considerably from beta-paramyosin. Mild, nonhydrolytic procedures employed by others to remove small, noncovalent bonded components or to separate protein complexes were not effective in converting alpha- to beta-paramyosin. Comparison of extraction procedures strongly supports the suggestion of Stafford and Yphantis that beta- and gamma-paramyosin are hydrolytic products of alpha-paramyosin and that the proteases responsible may be of bacterial origin.", "contents": "Comparison of solubility properties of alpha-paramyosin, beta-paramyosin and acid-extracted paramyosin. The solubility properties of paramyosin in the zones of pH and ionic strength in which aggregation occurs were initially studied using preparations isolated by a method originally described by Bailey (Bailey, K. (1956), Pubbl. Stn. Zool. Napoli 29, 26). Other preparations yielding apparently different protein components have been described by Hodge (Hodge, A.J. (1952), Proc. Natl. Acad. Sci., U.S.A. 38, 850) using acid conditions, and Stafford and Yphantis (Stafford, W.F., AND Yphantis, D. (1972), Biochem. Biophys. Res. Commun. 49, 848) have identified alpha-, beta-, and gamma-paramyosin using various times and temperatures of extraction with or without ethylenediaminetetraacetic acid. We have found that acid-extracted paramyosin is very similar if not identical to alpha-paramyosin, but that both acid and alpha forms differ considerably from beta- and gamma-paramyosin. Beta-Paramyosin precipitates abruptly from solution in narrow zone of pH below neutrality, and increases in ionic strength shift the zone of precipitation toward lower pH values. In contrast, both acid and alpha-paramyosin show gradual aggregation with changing pH at lowerionic strength (less than 0.3) but sharp transitions similar to beta-paramyosin at higher ionic strength (greater than 0.3). Transitions were also found at lower pH (ca. 4.0) which were not mirror images of transitions at higher pH (ca. 7.0). Viscosity measurements show that acid extracted paramyosin is close in behavior to a native extract obtained by extraction in mild, nondenaturing media containing mixed antibiotics. Each of these extracts differed considerably from beta-paramyosin. Mild, nonhydrolytic procedures employed by others to remove small, noncovalent bonded components or to separate protein complexes were not effective in converting alpha- to beta-paramyosin. Comparison of extraction procedures strongly supports the suggestion of Stafford and Yphantis that beta- and gamma-paramyosin are hydrolytic products of alpha-paramyosin and that the proteases responsible may be of bacterial origin."}
{"id": "PMID:16650", "title": "Cotransport of phosphate and sodium by yeast.", "content": "Phosphate uptake by yeast at pH 7.2 is mediated by two mechanisms, one of which has a Km of 30 micronM and is independent of sodium, and a sodium-dependent mechanism with a Km of 0.6 micronM, both Km values with respect to monovalent phosphate. The sodium-dependent mechanism has two sites with affinity for Na+, with affinity constants of 0.04 and 29 mM. Also lithium enhances phosphate uptake; the affinity constants for lithium are 0.3 and 36 mM. Other alkali ions do not stimulate phosphate uptake at pH 7.2. Ribidium has no effect on the stimulation of phosphate uptake by sodium. Phosphate and arsenate enhance sodium uptake at pH 7.2. The Km of this stimulation with regard to monovalent orthophosphate is about equal to that of the sodium-dependent phosphate uptake. The properties of the cation binding sites of the phosphate uptake mechanism and those of the phosphate-dependent cation transport mechanism have been compared. The existence of a separate sodium-phosphate cotransport system is proposed.", "contents": "Cotransport of phosphate and sodium by yeast. Phosphate uptake by yeast at pH 7.2 is mediated by two mechanisms, one of which has a Km of 30 micronM and is independent of sodium, and a sodium-dependent mechanism with a Km of 0.6 micronM, both Km values with respect to monovalent phosphate. The sodium-dependent mechanism has two sites with affinity for Na+, with affinity constants of 0.04 and 29 mM. Also lithium enhances phosphate uptake; the affinity constants for lithium are 0.3 and 36 mM. Other alkali ions do not stimulate phosphate uptake at pH 7.2. Ribidium has no effect on the stimulation of phosphate uptake by sodium. Phosphate and arsenate enhance sodium uptake at pH 7.2. The Km of this stimulation with regard to monovalent orthophosphate is about equal to that of the sodium-dependent phosphate uptake. The properties of the cation binding sites of the phosphate uptake mechanism and those of the phosphate-dependent cation transport mechanism have been compared. The existence of a separate sodium-phosphate cotransport system is proposed."}
{"id": "PMID:16651", "title": "Intracellular distribution of ribonuclease activity during erythroid cell development.", "content": "Five ribonuclease activities, separable by polyacrylamide gel electrophoresis, have been detected in erythroid bone marrow cells from anaemic rabbits. Their intracellular distribution has been investigated and compared with that of the ribonucleases in reticulocytes. Both the acid and alkaline ribonuclease activities of reticulocytes are much lower (30--50 fold) than those of bone marrow erythroid cells. The most marked decrease in enzyme activity occurs in the fractions containing ribosomes and mitochondria plus lysosomes. In these subcellular organelles there was also a qualitative change in the ribonuclease electrophoretic pattern, whereas the cytosol enzymes of marrow erythroid cells and reticulocytes remained largely unchanged. Several ribonucleases released from reticulocyte membranes with urea were similar to those present in the lysosomal plus mitochondrial fraction, as shown by detection of enzyme activity after polyacrylamide gel electrophoresis. The decline in ribonuclease activity was found to begin in the orthochromatic cells, which have a highly condensed nucleus and are no longer active in DNA and RNA synthesis, and to coincide with a decrease in acid phosphatase activity and loss of lysosomes.", "contents": "Intracellular distribution of ribonuclease activity during erythroid cell development. Five ribonuclease activities, separable by polyacrylamide gel electrophoresis, have been detected in erythroid bone marrow cells from anaemic rabbits. Their intracellular distribution has been investigated and compared with that of the ribonucleases in reticulocytes. Both the acid and alkaline ribonuclease activities of reticulocytes are much lower (30--50 fold) than those of bone marrow erythroid cells. The most marked decrease in enzyme activity occurs in the fractions containing ribosomes and mitochondria plus lysosomes. In these subcellular organelles there was also a qualitative change in the ribonuclease electrophoretic pattern, whereas the cytosol enzymes of marrow erythroid cells and reticulocytes remained largely unchanged. Several ribonucleases released from reticulocyte membranes with urea were similar to those present in the lysosomal plus mitochondrial fraction, as shown by detection of enzyme activity after polyacrylamide gel electrophoresis. The decline in ribonuclease activity was found to begin in the orthochromatic cells, which have a highly condensed nucleus and are no longer active in DNA and RNA synthesis, and to coincide with a decrease in acid phosphatase activity and loss of lysosomes."}
{"id": "PMID:16652", "title": "The essential activated carboxyl group of inorganic pyrophosphatase.", "content": "1. A carboxyl group of high reactivity has been found in inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) from yeast. This group interacts with agents which react neither with carboxyl groups of low molecular weight compounds nor with other carboxyl groups of the protein. 2. The reaction of this activated carboxyl group with inorganic phosphate, hydroxylamine, N-methyl- and O-methylhydroxylamines, and glycine methyl ester has been studied. 3. Homoserine and homoserine lactone were found in the hydrolyzate of phosphorylated and NaBH4-reduced pyrophosphatase, indicating that an aspartyl residue is phosphorylated. 4. Hydroxylamine and other nucleophilic agents cause inactivation of pyrophosphatase as a result of interaction with a carboxyl group. Both diaminobutyric and diaminopropionic acids were seen in the acid hydrolyzate of the protein treated with hydroxylamine and subjected to rearrangement in the presence of carbodiimide. 5. The ways in which the activation of a carboxyl group in the enzyme is achieved and the presumed mechanism of action of inorganic pyrophosphatase are discussed.", "contents": "The essential activated carboxyl group of inorganic pyrophosphatase. 1. A carboxyl group of high reactivity has been found in inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) from yeast. This group interacts with agents which react neither with carboxyl groups of low molecular weight compounds nor with other carboxyl groups of the protein. 2. The reaction of this activated carboxyl group with inorganic phosphate, hydroxylamine, N-methyl- and O-methylhydroxylamines, and glycine methyl ester has been studied. 3. Homoserine and homoserine lactone were found in the hydrolyzate of phosphorylated and NaBH4-reduced pyrophosphatase, indicating that an aspartyl residue is phosphorylated. 4. Hydroxylamine and other nucleophilic agents cause inactivation of pyrophosphatase as a result of interaction with a carboxyl group. Both diaminobutyric and diaminopropionic acids were seen in the acid hydrolyzate of the protein treated with hydroxylamine and subjected to rearrangement in the presence of carbodiimide. 5. The ways in which the activation of a carboxyl group in the enzyme is achieved and the presumed mechanism of action of inorganic pyrophosphatase are discussed."}
{"id": "PMID:16653", "title": "The stereospecificity of nitrate reductase for hydrogen removal from reduced pyridine nucleotides.", "content": "The stereospecificity of the hydrogen removal from reduced pyridine nucleotides catalyzed by nitrate reductase (NADH : nitrate oxidoreductase, EC 1.6.6.1, and NAD(P)H : nitrate oxidoreductase, EC 1.6.6.2) was investigated. A high degree of enzyme purification was required to obtain conclusive results. Improvements are described for the purification of nitrate reductase from Chlorella fusca and from spinach (Spinacea oleracea, L.) leaves. The latter enzyme is shown to contain a cytochrome. With highly purified nitrate reductase preparations from Cl. fusca, Neurospora crassa, Rhodotorula glutinis and spinach leaves the stereospecificity of the reaction was determined to be predominantly of the A-type in all cases.", "contents": "The stereospecificity of nitrate reductase for hydrogen removal from reduced pyridine nucleotides. The stereospecificity of the hydrogen removal from reduced pyridine nucleotides catalyzed by nitrate reductase (NADH : nitrate oxidoreductase, EC 1.6.6.1, and NAD(P)H : nitrate oxidoreductase, EC 1.6.6.2) was investigated. A high degree of enzyme purification was required to obtain conclusive results. Improvements are described for the purification of nitrate reductase from Chlorella fusca and from spinach (Spinacea oleracea, L.) leaves. The latter enzyme is shown to contain a cytochrome. With highly purified nitrate reductase preparations from Cl. fusca, Neurospora crassa, Rhodotorula glutinis and spinach leaves the stereospecificity of the reaction was determined to be predominantly of the A-type in all cases."}
{"id": "PMID:16655", "title": "Possible regulation of thiamine diphosphatase activity in rat brain microsomes by lipids.", "content": "The effects of various treatments, which affect membrane structure, on microsomal thiamine diphosphatase and thiamine triphosphatase activities of rat brain, were examined. The treatment of micorosomes at alkaline pH caused a 2-fold activation of the thiamine diphosphatase, this being related to a change in membrane structure which was evidenced by a decrease of the turbidity of the microsomal suspension. Repeated freezing and thawing after hypo-osmotic treatment also increased the activity of microsomal thiamine diphosphatase. In addition, the thiamine diphosphatase activity was enhanced by treatment of the microsomes with phospholipase C or acetone. This lipid depletion resulted in a marked reduction in the apparent Km value of the thiamine diphosphatase with a corresponding loss in heat stability of the enzyme. We found further that brain thiamine diphosphatase was solubilized by Triton X-100. This decreased the phospholipid content in the preparation, but did not affect the apparent Km value and heat stability of the enzyme. In contrast with thiamine diphosphatase, thiamine triphosphatase was inactivated by treatment at alkaline pH or with acetone. However, treatment with phospholipase C did not affect the activity of thiamine triphosphatase.", "contents": "Possible regulation of thiamine diphosphatase activity in rat brain microsomes by lipids. The effects of various treatments, which affect membrane structure, on microsomal thiamine diphosphatase and thiamine triphosphatase activities of rat brain, were examined. The treatment of micorosomes at alkaline pH caused a 2-fold activation of the thiamine diphosphatase, this being related to a change in membrane structure which was evidenced by a decrease of the turbidity of the microsomal suspension. Repeated freezing and thawing after hypo-osmotic treatment also increased the activity of microsomal thiamine diphosphatase. In addition, the thiamine diphosphatase activity was enhanced by treatment of the microsomes with phospholipase C or acetone. This lipid depletion resulted in a marked reduction in the apparent Km value of the thiamine diphosphatase with a corresponding loss in heat stability of the enzyme. We found further that brain thiamine diphosphatase was solubilized by Triton X-100. This decreased the phospholipid content in the preparation, but did not affect the apparent Km value and heat stability of the enzyme. In contrast with thiamine diphosphatase, thiamine triphosphatase was inactivated by treatment at alkaline pH or with acetone. However, treatment with phospholipase C did not affect the activity of thiamine triphosphatase."}
{"id": "PMID:16656", "title": "Inhibition of alkaline phosphatase by sialic acid.", "content": "The interaction of human organ alkaline phosphatases (orthophosphoric-monoester phosphohydrolases (alkaline optimum), EC 3.1.3.1) with sugars was studied. Hexosamines, N-acetylneuraminic acid (NANA or sialic acid), N-acetylmuramic acid and N-acetylglycolylneuraminic acid inhibited human organ alkaline phosphatase activities. Of these, sialic acid was the most effective inhibitor. The pH profiles for the enzymes in the absence and presence of sialic acid were similar. The sialic acid - enzyme complex was more heat stable than the free enzyme between 20 and 45 degrees C. Lineweaver-Burk plots of 1/v versus 1/S at various concentrations of sialic acid showed intersecting straight lines indicating that the mechanism of inhibition was a mixed type. The Ki value obtained from the plots of 1/v versus the square of sialic acid concentration was 0.07 mM for the hepatic, sialidase-treated hepatic, and intestinal alkaline phosphatases. The respective Hill coefficients varied somewhat with the alkaline phosphatase isoenzyme. Hyperbolic curves were obtained when the percentage of remaining activity was plotted against the substrate concentration at different concentrations of sialic acid. The Hill coefficient was lowered in the presence of sialic acid. The sialidase-treated hepatic enzymes used gave the most effective conversion. Partial denaturation of the enzyme with urea, or pronase digestion had a little if any effect on the sialic acid inhibition with constant time.", "contents": "Inhibition of alkaline phosphatase by sialic acid. The interaction of human organ alkaline phosphatases (orthophosphoric-monoester phosphohydrolases (alkaline optimum), EC 3.1.3.1) with sugars was studied. Hexosamines, N-acetylneuraminic acid (NANA or sialic acid), N-acetylmuramic acid and N-acetylglycolylneuraminic acid inhibited human organ alkaline phosphatase activities. Of these, sialic acid was the most effective inhibitor. The pH profiles for the enzymes in the absence and presence of sialic acid were similar. The sialic acid - enzyme complex was more heat stable than the free enzyme between 20 and 45 degrees C. Lineweaver-Burk plots of 1/v versus 1/S at various concentrations of sialic acid showed intersecting straight lines indicating that the mechanism of inhibition was a mixed type. The Ki value obtained from the plots of 1/v versus the square of sialic acid concentration was 0.07 mM for the hepatic, sialidase-treated hepatic, and intestinal alkaline phosphatases. The respective Hill coefficients varied somewhat with the alkaline phosphatase isoenzyme. Hyperbolic curves were obtained when the percentage of remaining activity was plotted against the substrate concentration at different concentrations of sialic acid. The Hill coefficient was lowered in the presence of sialic acid. The sialidase-treated hepatic enzymes used gave the most effective conversion. Partial denaturation of the enzyme with urea, or pronase digestion had a little if any effect on the sialic acid inhibition with constant time."}
{"id": "PMID:16657", "title": "Some properties of human liver acid alpha-glucosidase.", "content": "1. Albumin activates human liver acid alpha-glucosidase (alpha-D-glucoside hydrolase, EC 3.2.1.20). From the Arrhenius plot, pH-dependence and Lineweaver-Burk plots it can be concluded that this activation is not only due to stabilisation of the enzyme, but also influences the enzymatic activity. It is proposed that for optimal functioning human liver acid alpha-glucosidase needs a protein environment. 2. Glycogen has a competitive inhibitory effect on the hydrolysis of 4-methylumbelliferyl-alpha-D-glucopyranoside, in contrast to maltose which exhibits a non-competitive type of inhibition. It is concluded that two catalytic sites exist, one for glycogen and one for maltose, while both sites influence each other. With glycogen as substrate a break in the Arrhenius plot is found. This is not the case when maltose is used as substrate. 3. The effect of antibody raised against human liver acid alpha-glucosidase on the activity of human liver acid alpha-glucosidase is studied. No corss-reacting material could be demonstrated in the liver of a patient with glycogen storage disease Type II (M. Pompe, acid alpha-glucosidase deficiency).", "contents": "Some properties of human liver acid alpha-glucosidase. 1. Albumin activates human liver acid alpha-glucosidase (alpha-D-glucoside hydrolase, EC 3.2.1.20). From the Arrhenius plot, pH-dependence and Lineweaver-Burk plots it can be concluded that this activation is not only due to stabilisation of the enzyme, but also influences the enzymatic activity. It is proposed that for optimal functioning human liver acid alpha-glucosidase needs a protein environment. 2. Glycogen has a competitive inhibitory effect on the hydrolysis of 4-methylumbelliferyl-alpha-D-glucopyranoside, in contrast to maltose which exhibits a non-competitive type of inhibition. It is concluded that two catalytic sites exist, one for glycogen and one for maltose, while both sites influence each other. With glycogen as substrate a break in the Arrhenius plot is found. This is not the case when maltose is used as substrate. 3. The effect of antibody raised against human liver acid alpha-glucosidase on the activity of human liver acid alpha-glucosidase is studied. No corss-reacting material could be demonstrated in the liver of a patient with glycogen storage disease Type II (M. Pompe, acid alpha-glucosidase deficiency)."}
{"id": "PMID:16658", "title": "Lysosomal phospholipase A activities of rat ovarian tissue.", "content": "1.1. Lysosome-enriched fractions were prepared by differential centrifugation of homogenates of luteinized rats ovaries. Acid phospholipase A activities were characterized with [U-14C]diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-[9,10-3H]- or [1-14C]oleoyl-sn-glycero-3-phosphocholine as substrates. Acid phospholipase A1 activity had properties similar to other hydrolases of lysosomal origin; subcellular distribution, latency and acidic pH optimum. Acid phospholipase A2 activity with similar characteristics was also tentatively identified. We were unable to exclude the possibility that the combined action of phospholipase A1 and lysophospholipase contributed to the release of acyl moieties from the 2-position of the synthetic substrates. 2. Lysophospholipase activity was present in the lysosome-enriched fractions. This activity had an alkaline pH optimum. 3. Phospholipase A1 and A2 activities solubilized from lysosome fractions by freeze-thawing were inhibited by Ca2+ and slightly activated by EDTA. A Ca2+- stimulated phospholipase A2 activity, with an alkaline pH optimum, remained in the particulate residue of freeze-thawed lysosome preparations. This activity is believed to represent mitochondrial contamination. 4. Activities of acid phospholipase A, as well as other acid hydrolases, increased approx. 1.5-fold between 1 and 4 days following induction of luteinizatin, suggesting a hormonal influence on lysosomal enzyme activities.", "contents": "Lysosomal phospholipase A activities of rat ovarian tissue. 1.1. Lysosome-enriched fractions were prepared by differential centrifugation of homogenates of luteinized rats ovaries. Acid phospholipase A activities were characterized with [U-14C]diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-[9,10-3H]- or [1-14C]oleoyl-sn-glycero-3-phosphocholine as substrates. Acid phospholipase A1 activity had properties similar to other hydrolases of lysosomal origin; subcellular distribution, latency and acidic pH optimum. Acid phospholipase A2 activity with similar characteristics was also tentatively identified. We were unable to exclude the possibility that the combined action of phospholipase A1 and lysophospholipase contributed to the release of acyl moieties from the 2-position of the synthetic substrates. 2. Lysophospholipase activity was present in the lysosome-enriched fractions. This activity had an alkaline pH optimum. 3. Phospholipase A1 and A2 activities solubilized from lysosome fractions by freeze-thawing were inhibited by Ca2+ and slightly activated by EDTA. A Ca2+- stimulated phospholipase A2 activity, with an alkaline pH optimum, remained in the particulate residue of freeze-thawed lysosome preparations. This activity is believed to represent mitochondrial contamination. 4. Activities of acid phospholipase A, as well as other acid hydrolases, increased approx. 1.5-fold between 1 and 4 days following induction of luteinizatin, suggesting a hormonal influence on lysosomal enzyme activities."}
{"id": "PMID:16659", "title": "Phospholipase A in pulmonary secretions of patients with alveolar proteinosis.", "content": "This report presents evidence for the presence of phospholipase A2 (EC 3.1.1.4) activity in the insoluble pulmonary secretions of patients with alveolar proteinosis. The enzyme activity has a pH optimum between 7.5 and 8.5 and is stimulated by deoxycholate and Ca2+.", "contents": "Phospholipase A in pulmonary secretions of patients with alveolar proteinosis. This report presents evidence for the presence of phospholipase A2 (EC 3.1.1.4) activity in the insoluble pulmonary secretions of patients with alveolar proteinosis. The enzyme activity has a pH optimum between 7.5 and 8.5 and is stimulated by deoxycholate and Ca2+."}
{"id": "PMID:16660", "title": "Specific phospholipid requirement for activity of the purified respiratory chain NADH dehydrogenase of Escherichia coli.", "content": "The highly purified respiratory chain NADH dehydrogenase (EC 1.6.99.3) of Escherichia coli is inactive in the absence of detergent or phospholipid. Triton X-100 is the detergent that gives optimal activity, but the Triton X-100-activated enzyme is stimulated an additional 2-fold by E. coli phospholipids. Phosphatidylglycerol and diphosphatidylglycerol are the most effective lipid activators. The activated complex prepared with diphosphatidylglycerol is stable, whereas that with phosphatidylglycerol loses activity rapidly. Maximum activation by phospholipids occurs after preincubation at 0 degrees C and at pH 7. Triton X-100 is required at low concentrations for lipid activation, but high concentrations interfere with the activation. When the enzyme is optimally activated by phospholipids, it may be additionally activated 2-fold by spermidine, but not by magnesium. In contrast, the Triton X-100-activated form of the enzyme is stimulated by several divalent cations, without specificity. Thus, the most stable, active form of the purified NADH dehydrogenase is generated in the presence of diphosphatidylglycerol and spermidine.", "contents": "Specific phospholipid requirement for activity of the purified respiratory chain NADH dehydrogenase of Escherichia coli. The highly purified respiratory chain NADH dehydrogenase (EC 1.6.99.3) of Escherichia coli is inactive in the absence of detergent or phospholipid. Triton X-100 is the detergent that gives optimal activity, but the Triton X-100-activated enzyme is stimulated an additional 2-fold by E. coli phospholipids. Phosphatidylglycerol and diphosphatidylglycerol are the most effective lipid activators. The activated complex prepared with diphosphatidylglycerol is stable, whereas that with phosphatidylglycerol loses activity rapidly. Maximum activation by phospholipids occurs after preincubation at 0 degrees C and at pH 7. Triton X-100 is required at low concentrations for lipid activation, but high concentrations interfere with the activation. When the enzyme is optimally activated by phospholipids, it may be additionally activated 2-fold by spermidine, but not by magnesium. In contrast, the Triton X-100-activated form of the enzyme is stimulated by several divalent cations, without specificity. Thus, the most stable, active form of the purified NADH dehydrogenase is generated in the presence of diphosphatidylglycerol and spermidine."}
{"id": "PMID:16661", "title": "Effect of hydrophobic probes on the higher structure of D-amino acid oxidase.", "content": "1. The holoenzyme of D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3] was found to combine with 1-anilinonaphthalene-8-sulfonate without liberation of its coenzyme, FAD. No energy transfer interaction was found to occur between the bound dye and FAD of the holoenzyme. On the other hand, when the apoenzyme was bound to the dye and then to FAD, energy transfer interaction between the bound dye and bound FAD was observed. In both cases, the dye competes with the substrate, D-alanine. It is concluded that the dye bound to the holoenzyme is oriented in such a special manner that the mutual orientation factor between the dye and FAD becomes very small in magnitude. 2. When the apoenzyme combined with the dye, the monomer-dimer equilibrium of the apoenzyme shifted towards the dimer. On the other hand, 4-monobenzoylamido-4'-aminostilbene-2,2'-disulfonate combined with the apoenzyme to induce monomerization.", "contents": "Effect of hydrophobic probes on the higher structure of D-amino acid oxidase. 1. The holoenzyme of D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3] was found to combine with 1-anilinonaphthalene-8-sulfonate without liberation of its coenzyme, FAD. No energy transfer interaction was found to occur between the bound dye and FAD of the holoenzyme. On the other hand, when the apoenzyme was bound to the dye and then to FAD, energy transfer interaction between the bound dye and bound FAD was observed. In both cases, the dye competes with the substrate, D-alanine. It is concluded that the dye bound to the holoenzyme is oriented in such a special manner that the mutual orientation factor between the dye and FAD becomes very small in magnitude. 2. When the apoenzyme combined with the dye, the monomer-dimer equilibrium of the apoenzyme shifted towards the dimer. On the other hand, 4-monobenzoylamido-4'-aminostilbene-2,2'-disulfonate combined with the apoenzyme to induce monomerization."}
{"id": "PMID:16662", "title": "The interaction of histone H3 with histone H4 and with other histones studied by 19F nuclear magnetic resonance.", "content": "The behaviour, upon variations in ionic strength, pH and temperature of 19F nuclear nuclear magnetic resonance signals of the trifluoroacetonylated derivative of histone H3 is compared with those of the H3-H4 complex and of the Hv fraction (an equimolar mixture of H2A, H2B, H3 and h4). The line width of the 19F-labelled histone H3 signals increases with ionic strength or pH, an effect consistent with aggregation of the protein. In the case of H3-H4 complex or Hv the line width decreases at intermediate ionic strengths (0.1-0.25 M NaCl). This effect is interpreted as the consequence of the formation of a well defined structure with ionic strength. At high salt concentrations the line width increases as a consequence of the final rigid quaternary structure or of the formation of higher aggregates.", "contents": "The interaction of histone H3 with histone H4 and with other histones studied by 19F nuclear magnetic resonance. The behaviour, upon variations in ionic strength, pH and temperature of 19F nuclear nuclear magnetic resonance signals of the trifluoroacetonylated derivative of histone H3 is compared with those of the H3-H4 complex and of the Hv fraction (an equimolar mixture of H2A, H2B, H3 and h4). The line width of the 19F-labelled histone H3 signals increases with ionic strength or pH, an effect consistent with aggregation of the protein. In the case of H3-H4 complex or Hv the line width decreases at intermediate ionic strengths (0.1-0.25 M NaCl). This effect is interpreted as the consequence of the formation of a well defined structure with ionic strength. At high salt concentrations the line width increases as a consequence of the final rigid quaternary structure or of the formation of higher aggregates."}
{"id": "PMID:16664", "title": "The denaturation of beta-lactoglobulin-A at pH 2.", "content": "The denaturation of beta-lactoglobulin-A by heat and guanidine hydrochloride at pH 2 has been investigated. The effect of ethylene glycol on the thermal denaturation at this pH has also been studied. The conditions of the experiments have been chosen so as to eliminate complications arising out of disulfide interchange, changes in the degree of association of the protein during denaturation, and intermolecular aggregation. The physical parameters characterizing the denatured states of the protein which are produced by heat and guanidine hydrochloride have been determined. The thermodynamic parameters for these transitions have been estimated using a two-state hypothesis in each case. Both the physical and thermodynamic parameters indicate that the heat-denatured state of beta-lactoglobulin-A retains about 15-20% of residual structure which is destroyed on adding guanidine hydrochloride.", "contents": "The denaturation of beta-lactoglobulin-A at pH 2. The denaturation of beta-lactoglobulin-A by heat and guanidine hydrochloride at pH 2 has been investigated. The effect of ethylene glycol on the thermal denaturation at this pH has also been studied. The conditions of the experiments have been chosen so as to eliminate complications arising out of disulfide interchange, changes in the degree of association of the protein during denaturation, and intermolecular aggregation. The physical parameters characterizing the denatured states of the protein which are produced by heat and guanidine hydrochloride have been determined. The thermodynamic parameters for these transitions have been estimated using a two-state hypothesis in each case. Both the physical and thermodynamic parameters indicate that the heat-denatured state of beta-lactoglobulin-A retains about 15-20% of residual structure which is destroyed on adding guanidine hydrochloride."}
{"id": "PMID:16667", "title": "[Influence of pH on the steady state kinetics of electron transfer through the cytochrome chain of submitochondrial particles. Kinetic model for regulating the activity of carriers by the local concentration of hydrogen ions in the membrane].", "content": "The kinetic parameters of the submitochondrial particles cytochrome chain obtained from steady-state kinetics were studied for pH dependence. The life-times of the activated states (tau) for cytochrome pairs b leads to c1 and a leads to a3 are shown to bear dissimilar dependence on pH of the medium, while for cytochrome pairs c1 leads to c and c leads to a they display practically no pH dependence at all. The rate constants of the non-activated state (alphai-kiCo) decreased for the pair b leads to c1 and increased for a leads to a3 with the increase of pH from 6.5 to 8.5. The apparent pK values obtained therefrom were 7.2 and 8.9, respectively. A kinetic model is proposed suggesting that local pH in the mitochondrial membrane, dependent on the rate of electron transfer, may be a controlling factor for the ratio of activated and non-activated carrier states. The model is in good consistence with the experimental dependences of k'i on V and the pH dependences of alpha2 for b leads to c1 and a leads to a3. It also gives a qualitative prediction for the pH dependences of the ordinate intercepts of the straight lines in l/(k'i--alphai) vs. l/V plots. The rate constants for the diffusion of hydrogen and hydroxyl ions in the membrane are estimated on the basis of our kinetic data to be 10(4)--10(5) s-1 and 10(2)--10(3) s-i, respectively.", "contents": "[Influence of pH on the steady state kinetics of electron transfer through the cytochrome chain of submitochondrial particles. Kinetic model for regulating the activity of carriers by the local concentration of hydrogen ions in the membrane]. The kinetic parameters of the submitochondrial particles cytochrome chain obtained from steady-state kinetics were studied for pH dependence. The life-times of the activated states (tau) for cytochrome pairs b leads to c1 and a leads to a3 are shown to bear dissimilar dependence on pH of the medium, while for cytochrome pairs c1 leads to c and c leads to a they display practically no pH dependence at all. The rate constants of the non-activated state (alphai-kiCo) decreased for the pair b leads to c1 and increased for a leads to a3 with the increase of pH from 6.5 to 8.5. The apparent pK values obtained therefrom were 7.2 and 8.9, respectively. A kinetic model is proposed suggesting that local pH in the mitochondrial membrane, dependent on the rate of electron transfer, may be a controlling factor for the ratio of activated and non-activated carrier states. The model is in good consistence with the experimental dependences of k'i on V and the pH dependences of alpha2 for b leads to c1 and a leads to a3. It also gives a qualitative prediction for the pH dependences of the ordinate intercepts of the straight lines in l/(k'i--alphai) vs. l/V plots. The rate constants for the diffusion of hydrogen and hydroxyl ions in the membrane are estimated on the basis of our kinetic data to be 10(4)--10(5) s-1 and 10(2)--10(3) s-i, respectively."}
{"id": "PMID:16668", "title": "[Properties of alpha-chymotrypsin and cis-cinnamoylchymotrypsin in free, covalently bound to a carrier and microcapsulated states].", "content": "alpha-Chymotrypsin and its light-sensitive derivative, cis-cinnamoylchymotrypsin, free and immobilysed (by means of microcapsulation, covalent binding with sepharose 4B and p-aminobenzyl cellulose) are studied. Effect of pH on the hydrolysis rate of N-alpha-acetyl-L-tyrosine ethyl ester by different immobilized enzyme preparations, their acylation with isomeric mixture of cis- and trans-cinnamoylimidazole, reactivation of stable cis-derivatives of different enzyme samples and thermal stability of native and microcapsulated enzyme preparations are investigated.", "contents": "[Properties of alpha-chymotrypsin and cis-cinnamoylchymotrypsin in free, covalently bound to a carrier and microcapsulated states]. alpha-Chymotrypsin and its light-sensitive derivative, cis-cinnamoylchymotrypsin, free and immobilysed (by means of microcapsulation, covalent binding with sepharose 4B and p-aminobenzyl cellulose) are studied. Effect of pH on the hydrolysis rate of N-alpha-acetyl-L-tyrosine ethyl ester by different immobilized enzyme preparations, their acylation with isomeric mixture of cis- and trans-cinnamoylimidazole, reactivation of stable cis-derivatives of different enzyme samples and thermal stability of native and microcapsulated enzyme preparations are investigated."}
{"id": "PMID:16669", "title": "[Role of low-molecular weight factors isolated from Methanobacillus kuzneceovii in the activating effect of visible light on methane formation and reduction of pyridine nucleotides].", "content": "Four low molecular weight fluorescent factors are isolated from thermophylic methaneproducing facteria Methanobacterium kuzneceovii. These factors are: the factor 340; the factor 420 (both reduced and oxidized); and a flavine derivative, comprising together with proteins a biochemical system, which reduces pyridine nucleotides in dark (at 55degrees C) and in the light (at 21degrees C).", "contents": "[Role of low-molecular weight factors isolated from Methanobacillus kuzneceovii in the activating effect of visible light on methane formation and reduction of pyridine nucleotides]. Four low molecular weight fluorescent factors are isolated from thermophylic methaneproducing facteria Methanobacterium kuzneceovii. These factors are: the factor 340; the factor 420 (both reduced and oxidized); and a flavine derivative, comprising together with proteins a biochemical system, which reduces pyridine nucleotides in dark (at 55degrees C) and in the light (at 21degrees C)."}
{"id": "PMID:16670", "title": "The effect of birth on the maturation of hepatic cytochrome(s) P-450 mono-oxygenase and tyrosine aminotransferase activities in the guinea pig.", "content": "Mixed coat guinea pigs delivered by Cesarian section 5 days before term were compared to spontaneously delivered full-term animals with respect to the postnatal maturation of hepatic mono-oxygenase activity in vitro toward aniline and p-chloro-N-methylaniline. Tyrosine aminotransferase acitivity was studied in the same preparations as a positive control for birth-related phenomena. Mono-oxygenase activities toward both sustrates increased significantly in both premature and full-term animals during the first 3 postnatal days and approached adult values 72 h after birth. The maturation of tyrosine aminotransferase activity occured in a qualitatively similar fashion. The mechanism through which birth initiates the maturation of drug oxidative capacity is unresolved; the gestational age at which competence to respond to the event of birth is acquired, remains undefined.", "contents": "The effect of birth on the maturation of hepatic cytochrome(s) P-450 mono-oxygenase and tyrosine aminotransferase activities in the guinea pig. Mixed coat guinea pigs delivered by Cesarian section 5 days before term were compared to spontaneously delivered full-term animals with respect to the postnatal maturation of hepatic mono-oxygenase activity in vitro toward aniline and p-chloro-N-methylaniline. Tyrosine aminotransferase acitivity was studied in the same preparations as a positive control for birth-related phenomena. Mono-oxygenase activities toward both sustrates increased significantly in both premature and full-term animals during the first 3 postnatal days and approached adult values 72 h after birth. The maturation of tyrosine aminotransferase activity occured in a qualitatively similar fashion. The mechanism through which birth initiates the maturation of drug oxidative capacity is unresolved; the gestational age at which competence to respond to the event of birth is acquired, remains undefined."}
{"id": "PMID:16671", "title": "Human cytomegalovirus. A review of developments between 1970 and 1976. I. Clinical developments.", "content": "Cytomegalovirus (CMV), like other members of the herpesviruses, is widely distributed in human populations where the frequency of seropositive individuals is influenced by such factors as age, sex and socio-economic conditions. While this virus causes such diseases as mononucleosis, it is also implicated in autoimmune phenomena and plays an adverse role renal and bone marrow transplantation. Perhaps the most menacing aspect of CMV is the role which it play in congenital malformations resulting from  in utero or neo-natal infection. Indeed, this virus is one of the few which can be transmitted vertically. The above mentioned clinical aspects of CMV are discussed here in light of recent clinically studies. The second part of this review will be devoted to the great mass of information recently acquired through experimentation.", "contents": "Human cytomegalovirus. A review of developments between 1970 and 1976. I. Clinical developments. Cytomegalovirus (CMV), like other members of the herpesviruses, is widely distributed in human populations where the frequency of seropositive individuals is influenced by such factors as age, sex and socio-economic conditions. While this virus causes such diseases as mononucleosis, it is also implicated in autoimmune phenomena and plays an adverse role renal and bone marrow transplantation. Perhaps the most menacing aspect of CMV is the role which it play in congenital malformations resulting from  in utero or neo-natal infection. Indeed, this virus is one of the few which can be transmitted vertically. The above mentioned clinical aspects of CMV are discussed here in light of recent clinically studies. The second part of this review will be devoted to the great mass of information recently acquired through experimentation."}
{"id": "PMID:16672", "title": "The effects of adrenergic agonists and blockers on antigen-induced DNA synthesis in vitro.", "content": "The effects of both alpha and beta adrenergic agonists and blockers on antigen-stimulated DNA synthesis in human lymphocyte cultures were studied. Results show that antigen-induced responses were enhanced by the presence of the beta blockers, propranolol and dichloroisoproterenol, and that this effect appeared to be specific blocking of the lymphocyte beta receptor since D (+) propranolol, a compound devoid of such acitvity, has no effect. Similarly, and alpha adrenergic agonist such as norepinephrine enhanced lymphocyte responsiveness.", "contents": "The effects of adrenergic agonists and blockers on antigen-induced DNA synthesis in vitro. The effects of both alpha and beta adrenergic agonists and blockers on antigen-stimulated DNA synthesis in human lymphocyte cultures were studied. Results show that antigen-induced responses were enhanced by the presence of the beta blockers, propranolol and dichloroisoproterenol, and that this effect appeared to be specific blocking of the lymphocyte beta receptor since D (+) propranolol, a compound devoid of such acitvity, has no effect. Similarly, and alpha adrenergic agonist such as norepinephrine enhanced lymphocyte responsiveness."}
{"id": "PMID:16674", "title": "[Lactic acid as a  factor in altering vascular reactivity].", "content": "It was shown that the constrictor responses to the electrostimulation of the isolated vessel segments were replaced by dilatation when the drugs were contained in the lactic acid solution. The capacity to constrictor effects was not lost completely, but these effects appeared in repsonse to the intensive stimulation. Changes in the character of these reactions to the electrostimulation were connected with the changes in the pH of the solution, as well as with the specific action of lactic acid.", "contents": "[Lactic acid as a  factor in altering vascular reactivity]. It was shown that the constrictor responses to the electrostimulation of the isolated vessel segments were replaced by dilatation when the drugs were contained in the lactic acid solution. The capacity to constrictor effects was not lost completely, but these effects appeared in repsonse to the intensive stimulation. Changes in the character of these reactions to the electrostimulation were connected with the changes in the pH of the solution, as well as with the specific action of lactic acid."}
{"id": "PMID:16675", "title": "[Graft vs host reaction in reciprocal combinations of mouse strains differing by the H-2 complex of histocompatibility].", "content": "Intraperitoneal transplantation of 0.5 x 10(7), 1 x 10(7) or 2 x 10(7) spleen cells from the C57BL mice to newborn CBA recipients induced an acute form or runt disease which resulted in the death of 43%, 86% or 95% of the recipient mice, respectively, in the course of 2--3 weeks after the cell transfer. Preliminary immunization of C57BL donors with CBA isoantigens led to a marked enhancement, and immunization with foreign antigens (sheep red blood cells)--to weakening the reaction. In reverse combination of mouse strains the runt disease was 4--5 times less severe and no \"preimmunization effect\" occurred. In C57BL leads to CBA combination the reaction was accompanied by proliferation of pyroninophilic mononuclears and follicular destruction, while in the CBA leads to C57BL combination-by the retardation of their growth.", "contents": "[Graft vs host reaction in reciprocal combinations of mouse strains differing by the H-2 complex of histocompatibility]. Intraperitoneal transplantation of 0.5 x 10(7), 1 x 10(7) or 2 x 10(7) spleen cells from the C57BL mice to newborn CBA recipients induced an acute form or runt disease which resulted in the death of 43%, 86% or 95% of the recipient mice, respectively, in the course of 2--3 weeks after the cell transfer. Preliminary immunization of C57BL donors with CBA isoantigens led to a marked enhancement, and immunization with foreign antigens (sheep red blood cells)--to weakening the reaction. In reverse combination of mouse strains the runt disease was 4--5 times less severe and no \"preimmunization effect\" occurred. In C57BL leads to CBA combination the reaction was accompanied by proliferation of pyroninophilic mononuclears and follicular destruction, while in the CBA leads to C57BL combination-by the retardation of their growth."}
{"id": "PMID:16681", "title": "Blood pressure and heart rate and withdrawal of antihypertensive drugs.", "content": "The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets.", "contents": "Blood pressure and heart rate and withdrawal of antihypertensive drugs. The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets."}
{"id": "PMID:16678", "title": "[Blood gas measurements and automatization (author's transl)].", "content": "The Corning 175, a fully automatic new blood-gas analyzer, was tested and compared with manual analyzers (Eschweiler-Radiometer). The precision was evaluated by means of tonometered bloods and precision gas mixtures. With the Corning 175 four parameters are measured: pH, PCO2, PO2, barometric pressure, and four computed: HCO3-, BE, oxygen content, oxygen saturation. These are automatically corrected for patient hemoglobin and temperature. A microprocessor controls the sequencing of all operations during the calibrations and the measurements and continuously checks the performances of the electrodes and the entire system. The operator part is limited to the introduction of blood. The advantages and the fiability of the automatism in clinical routine are described.", "contents": "[Blood gas measurements and automatization (author's transl)]. The Corning 175, a fully automatic new blood-gas analyzer, was tested and compared with manual analyzers (Eschweiler-Radiometer). The precision was evaluated by means of tonometered bloods and precision gas mixtures. With the Corning 175 four parameters are measured: pH, PCO2, PO2, barometric pressure, and four computed: HCO3-, BE, oxygen content, oxygen saturation. These are automatically corrected for patient hemoglobin and temperature. A microprocessor controls the sequencing of all operations during the calibrations and the measurements and continuously checks the performances of the electrodes and the entire system. The operator part is limited to the introduction of blood. The advantages and the fiability of the automatism in clinical routine are described."}
{"id": "PMID:16685", "title": "Transmitter histochemistry of the rat olfactory bulb. I. Immunohistochemical localization of monoamine synthesizing enzymes. Support for intrabulbar, periglomerular dopamine neurons.", "content": "The rat olfactory bulb was studied at the light and electron microscopic level with the indirect immunofluorescence technique and the unlabelled antibody enzyme method (PAP-technique), respectively. Antibodies to all 4 enzymes in the catecholamine synthesis were used. In the principal bulb the first two enzymes, tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC), but not dopamine-beta-hydroxylase (DBH), were present in a proportion of periglomerular cell bodies and dendrites indicating that these neurons synthesize dopamine (DA). This amine may therefore be released as a transmitter substance at some of the intraglomerular dendrodendritic synapses which periglomerular cells form with the mitral cells. There is evidence to suggest that some periglomerular cells use GABA as their transmitter. Thus, a morphologically and physiologically homogenous population of neurons can be subdivided on the basis of transmitter histochemical criteria. There was an impression of more DDC-positive than TH-positive fibers in the glomeruli. Such presumably DDC-positive, but TH-negative processes may represent 5-hydroxytryptamine (5-HT) nerve terminals. DBH-positive fibers were seen in the granular, external plexiform, and very rarely, in the glomerular layers, probably representing noradrenaline (NA) nerve terminals ascending from the lower brain stem. Weakly fluorescent DDC-positive fibers may represent nerve terminals of ascending 5-HT neurons. No phenylethanolamine-N-methyltransferase (PNMT)-positive neurons were observed.", "contents": "Transmitter histochemistry of the rat olfactory bulb. I. Immunohistochemical localization of monoamine synthesizing enzymes. Support for intrabulbar, periglomerular dopamine neurons. The rat olfactory bulb was studied at the light and electron microscopic level with the indirect immunofluorescence technique and the unlabelled antibody enzyme method (PAP-technique), respectively. Antibodies to all 4 enzymes in the catecholamine synthesis were used. In the principal bulb the first two enzymes, tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC), but not dopamine-beta-hydroxylase (DBH), were present in a proportion of periglomerular cell bodies and dendrites indicating that these neurons synthesize dopamine (DA). This amine may therefore be released as a transmitter substance at some of the intraglomerular dendrodendritic synapses which periglomerular cells form with the mitral cells. There is evidence to suggest that some periglomerular cells use GABA as their transmitter. Thus, a morphologically and physiologically homogenous population of neurons can be subdivided on the basis of transmitter histochemical criteria. There was an impression of more DDC-positive than TH-positive fibers in the glomeruli. Such presumably DDC-positive, but TH-negative processes may represent 5-hydroxytryptamine (5-HT) nerve terminals. DBH-positive fibers were seen in the granular, external plexiform, and very rarely, in the glomerular layers, probably representing noradrenaline (NA) nerve terminals ascending from the lower brain stem. Weakly fluorescent DDC-positive fibers may represent nerve terminals of ascending 5-HT neurons. No phenylethanolamine-N-methyltransferase (PNMT)-positive neurons were observed."}
{"id": "PMID:16686", "title": "Striatal lesions with kainic acid: neurochemical characteristics.", "content": "Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region.", "contents": "Striatal lesions with kainic acid: neurochemical characteristics. Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region."}
{"id": "PMID:16690", "title": "Methylamine dehydrogenase from the obligate methylotroph Methylomonas methylovora.", "content": "An obligate methyltroph Methylomonas methylovora oxidized methylamine, formaldehyde, and formate. Enzymes oxidizing these substrates were detected in a cell-free system. Phenazine methosulfate-linked methylamine dehydrogenase was purified 21-fold. The enzyme had optimum activity at pH 7.5 and was stable at 60 degrees C for 5 min. The enzyme activity was inhibited by parachloromercuric benzoate, isonicotinic acid hydrazide, mercuric chloride, and sodium borate.", "contents": "Methylamine dehydrogenase from the obligate methylotroph Methylomonas methylovora. An obligate methyltroph Methylomonas methylovora oxidized methylamine, formaldehyde, and formate. Enzymes oxidizing these substrates were detected in a cell-free system. Phenazine methosulfate-linked methylamine dehydrogenase was purified 21-fold. The enzyme had optimum activity at pH 7.5 and was stable at 60 degrees C for 5 min. The enzyme activity was inhibited by parachloromercuric benzoate, isonicotinic acid hydrazide, mercuric chloride, and sodium borate."}
{"id": "PMID:16691", "title": "Partial purification and some properties of a neutral sulfhydryl and an acid proteinase from Entamoeba histolytica.", "content": "The partial purification of two intracellular proteinases from the protozoan parasite Entamoeba histolytica is reported. One of these enzymes is an acid proteinase exhibiting maximum activity at pH 3.5 (hemoglobin substrate), is little affected by a range of inhibitors or activators, and is presumed to be similar to cathepsin D. Also present is a neutral proteinase exhibiting optimum activity at pH 6.0 (azocasein) but only poorly hydrolyzing either hemoglobin or serum albumen. This latter enzyme displayed no metal ion requirement, but was markedly inhibited by thiol-blocking agents and activated by free sulhydryl-containing compounds.", "contents": "Partial purification and some properties of a neutral sulfhydryl and an acid proteinase from Entamoeba histolytica. The partial purification of two intracellular proteinases from the protozoan parasite Entamoeba histolytica is reported. One of these enzymes is an acid proteinase exhibiting maximum activity at pH 3.5 (hemoglobin substrate), is little affected by a range of inhibitors or activators, and is presumed to be similar to cathepsin D. Also present is a neutral proteinase exhibiting optimum activity at pH 6.0 (azocasein) but only poorly hydrolyzing either hemoglobin or serum albumen. This latter enzyme displayed no metal ion requirement, but was markedly inhibited by thiol-blocking agents and activated by free sulhydryl-containing compounds."}
{"id": "PMID:16692", "title": "Lawnmower injuries in children.", "content": "Over an 8-year period 31 children in the Winnipeg area were admitted to hospital with lawnmower injuries. The accidents were always preventable and were caused by patient or parent carelessness. The wounds were severe, often resulting in amputation of a portion of an extremity. Infection was common; prophylaxis with a broad-spectrum antibiotic and human antitetanus globulin is recommended. Radiography, d\u00e9bridement of the wound with thorough exploration under general anesthesia, and defatting and reapplication of degloved skin should be done initially, then the wound should be reinspected and redressed at 2 to 3 days, and finally closed or skin grafted at 6 to 8 days. Children must be educated about the dangers of lawnmowers and prevented from riding on tractor mowers. The grass catcher should be used and the path cleared of missiles. Hand controls should be mounted on the mower's handle and the blade should be kept sharp so that the machine's speed can be reduced.", "contents": "Lawnmower injuries in children. Over an 8-year period 31 children in the Winnipeg area were admitted to hospital with lawnmower injuries. The accidents were always preventable and were caused by patient or parent carelessness. The wounds were severe, often resulting in amputation of a portion of an extremity. Infection was common; prophylaxis with a broad-spectrum antibiotic and human antitetanus globulin is recommended. Radiography, d\u00e9bridement of the wound with thorough exploration under general anesthesia, and defatting and reapplication of degloved skin should be done initially, then the wound should be reinspected and redressed at 2 to 3 days, and finally closed or skin grafted at 6 to 8 days. Children must be educated about the dangers of lawnmowers and prevented from riding on tractor mowers. The grass catcher should be used and the path cleared of missiles. Hand controls should be mounted on the mower's handle and the blade should be kept sharp so that the machine's speed can be reduced."}
{"id": "PMID:16694", "title": "An endo-(1 leads to 3)-beta-D-glucanase from Mucor hiemalis.", "content": "An endo-(1 leads to 3)-beta-D-glucanase (EC 3.2.1.6), isolated from the culture filtrate of the fungus Mucor hiemalis, was purified by ammonium sulfate fractionation, gel filtration, and column chromatography on O-(carboxymethyl)cellulose. The optimum pH, optimum temperature, and Km value of the enzyme were pH 5.0, 50 degrees, and 0.048%, respectively. The enzyme was strongly inactivated by Pb2+, Cu2+, and Hg2+ ions and also inhibited by Zn2+ and Fe3+ ions. The enzyme was specific for laminaran and the action pattern of the enzyme was of the endo-type. The molecular weight of the enzyme, as determined by gel filtration, was 30,000.", "contents": "An endo-(1 leads to 3)-beta-D-glucanase from Mucor hiemalis. An endo-(1 leads to 3)-beta-D-glucanase (EC 3.2.1.6), isolated from the culture filtrate of the fungus Mucor hiemalis, was purified by ammonium sulfate fractionation, gel filtration, and column chromatography on O-(carboxymethyl)cellulose. The optimum pH, optimum temperature, and Km value of the enzyme were pH 5.0, 50 degrees, and 0.048%, respectively. The enzyme was strongly inactivated by Pb2+, Cu2+, and Hg2+ ions and also inhibited by Zn2+ and Fe3+ ions. The enzyme was specific for laminaran and the action pattern of the enzyme was of the endo-type. The molecular weight of the enzyme, as determined by gel filtration, was 30,000."}
{"id": "PMID:16701", "title": "Effect of streptovaricin on the incorporation of uridine into cellular and viral RNA.", "content": "Poxvirus replication is inhibited by streptovaricin. The most readily observed effect is the inhibition of incorporation of [3H]uridine into viral mRNA, suggesting an inhibition of RNA synthesis. Streptovaricin also inhibits the incorporation of [3H]uridine into cellular RNA but not as severely as viral RNA. On the other hand, [3H]uridine incorporation into the RNA of Semliki Forest virus (SFV), which contains a positive strand RNA genome, does not seem to be inhibited by streptovaricin. The inhibitory effect of streptovaricin is completely reversible after removal of the inhibitor. In addition to inhibiting RNA synthesis, streptovaricin also may inhibit the methylation of cellular RNA. Viral RNA is stable in the presence of streptovaricin.", "contents": "Effect of streptovaricin on the incorporation of uridine into cellular and viral RNA. Poxvirus replication is inhibited by streptovaricin. The most readily observed effect is the inhibition of incorporation of [3H]uridine into viral mRNA, suggesting an inhibition of RNA synthesis. Streptovaricin also inhibits the incorporation of [3H]uridine into cellular RNA but not as severely as viral RNA. On the other hand, [3H]uridine incorporation into the RNA of Semliki Forest virus (SFV), which contains a positive strand RNA genome, does not seem to be inhibited by streptovaricin. The inhibitory effect of streptovaricin is completely reversible after removal of the inhibitor. In addition to inhibiting RNA synthesis, streptovaricin also may inhibit the methylation of cellular RNA. Viral RNA is stable in the presence of streptovaricin."}
{"id": "PMID:16704", "title": "[Control of pituitary secretion of melanotropin in an anuran amphibian by thyrotropin releasing factor (TRH). Study in vitro].", "content": "Intermediate lobes from Rana esculenta pituitary glands were continuously superfused for 7 hrs at 28 degrees C with amphibian culture medium. alpha-MSH release was measured by use of a sensitive double antibody radio-immunoassay system. alpha-MSH secretion was inhibited by low temperatures. A large increase in alpha-MSH release was observed when Thyrotropin Releasing Hormone (TRH) at doses ranging from 10(-9) to 10(-7) molar was added to the superfusion medium. Since large amounts of TRH are to be found in the hypothalamus of amphibians but have no effect over pituitary TSH secretion, the action of TRH over alpha-MSH release may have a physiological significance.", "contents": "[Control of pituitary secretion of melanotropin in an anuran amphibian by thyrotropin releasing factor (TRH). Study in vitro]. Intermediate lobes from Rana esculenta pituitary glands were continuously superfused for 7 hrs at 28 degrees C with amphibian culture medium. alpha-MSH release was measured by use of a sensitive double antibody radio-immunoassay system. alpha-MSH secretion was inhibited by low temperatures. A large increase in alpha-MSH release was observed when Thyrotropin Releasing Hormone (TRH) at doses ranging from 10(-9) to 10(-7) molar was added to the superfusion medium. Since large amounts of TRH are to be found in the hypothalamus of amphibians but have no effect over pituitary TSH secretion, the action of TRH over alpha-MSH release may have a physiological significance."}
{"id": "PMID:16705", "title": "[Spontaneous phospholipase A activity of rat pancreatic homogenates].", "content": "Rat pancreas presents a spontaneous phospholipase A activity which appears before trypsin activation at optimal pH 6.5. The responsible enzyme is independent of pancreatic prophospholipase A, as can be seen through experiments done in the presence of trypsin inhibitors. On the other hand, this enzyme is distinct from excretory phospholipase which is more active and whose optimal pH is 8.8. Thermostability and insensibility of spontaneously active phospholipase A to DFP differentiate it from lipase, carboxyl-esterhydrolase and lysophospholipase, respectively.", "contents": "[Spontaneous phospholipase A activity of rat pancreatic homogenates]. Rat pancreas presents a spontaneous phospholipase A activity which appears before trypsin activation at optimal pH 6.5. The responsible enzyme is independent of pancreatic prophospholipase A, as can be seen through experiments done in the presence of trypsin inhibitors. On the other hand, this enzyme is distinct from excretory phospholipase which is more active and whose optimal pH is 8.8. Thermostability and insensibility of spontaneously active phospholipase A to DFP differentiate it from lipase, carboxyl-esterhydrolase and lysophospholipase, respectively."}
{"id": "PMID:16707", "title": "Studies on alkaline phosphatase isoenzymes. Relation to gamma-glutamyltransferase and lactate dehydrogenase isoenzymes.", "content": "Gamma-Glutamyltransferase (GT) and isoenzymes of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been studied in 282 cases with increased S-ALP and in 18 chronic alcoholics with normal routine liver tests. There was a high degree of correlation between S-GT and the bile (alpha 1) and liver (alpha 2) fractions of S-ALP. Fractionation of alkaline phosphatases sometimes yielded clinical information, which could not be obtained by determinations of S-ALP and S-GT only. The presence of alpha 1-ALP and increased S-GT appeared to be more sensitive indicators of ethanol-induced liver involvement than other liver tests, including LDH-5/LDH-4 ratios.", "contents": "Studies on alkaline phosphatase isoenzymes. Relation to gamma-glutamyltransferase and lactate dehydrogenase isoenzymes. Gamma-Glutamyltransferase (GT) and isoenzymes of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been studied in 282 cases with increased S-ALP and in 18 chronic alcoholics with normal routine liver tests. There was a high degree of correlation between S-GT and the bile (alpha 1) and liver (alpha 2) fractions of S-ALP. Fractionation of alkaline phosphatases sometimes yielded clinical information, which could not be obtained by determinations of S-ALP and S-GT only. The presence of alpha 1-ALP and increased S-GT appeared to be more sensitive indicators of ethanol-induced liver involvement than other liver tests, including LDH-5/LDH-4 ratios."}
{"id": "PMID:16703", "title": "[Incidence of Arbovirus isolated from mosquitoes in the forest region of South Cameroun, region of Yaound\u00e9 ].", "content": "The authors give results of a survey of arboviruses isolated from mosquitoes in the neighborhood of Yaound\u00e9, Southern Cameroon, from 1964 to 1972. During this period of nine years 127.520 female mosquitoes including at least 72 species were collected and processed for attempt of virus isolation. 55 strains belonging to 12 viral types were recovered from at least 19 species of mosquitoes. The appearance of different viruses over the years was quite intermittent. A possible reason for this is the need for viruses to move in search of susceptible vertebrate hosts. There was not definite evidence of vector host specificity except likely for Anopheles gambiae s. l. as a vector of Tataguine. However, among the more infected species, some ones show by their host preferences they could be true vectors of the viruses isolated from them.", "contents": "[Incidence of Arbovirus isolated from mosquitoes in the forest region of South Cameroun, region of Yaound\u00e9 ]. The authors give results of a survey of arboviruses isolated from mosquitoes in the neighborhood of Yaound\u00e9, Southern Cameroon, from 1964 to 1972. During this period of nine years 127.520 female mosquitoes including at least 72 species were collected and processed for attempt of virus isolation. 55 strains belonging to 12 viral types were recovered from at least 19 species of mosquitoes. The appearance of different viruses over the years was quite intermittent. A possible reason for this is the need for viruses to move in search of susceptible vertebrate hosts. There was not definite evidence of vector host specificity except likely for Anopheles gambiae s. l. as a vector of Tataguine. However, among the more infected species, some ones show by their host preferences they could be true vectors of the viruses isolated from them."}
{"id": "PMID:16708", "title": "Comparison of human membrane-bound neutral arylamidases from small intestine, lung, kidney, liver and placenta.", "content": "Human membrane-bound neutral arylamidases were solubilized from small intestinal mucosa, lung, kidney, liver and placenta with trypsin. These five membrane-bound neutral arylamidases were identified by polyacrylamide gel-disc electrophoresis. The heat sensitivity of each enzyme was in the order, liver and placenta greater than kidney greater than lung greater than small intestine. This order correlates with that of electrophoretic mobility, except for the placental membrane-bound neutral arylamidase. Five membrane-bound neutral arylamidases have the same molecular weight, 240 000, as estimated by Sephadex G-200 gel filtration. The five membrane-bound neutral arylamidase have very similar KM values (8.7 x 10(-5) M towards L-alanyl-beta-naphthylamide), optimal pH values, hydrolysis ratios towards L-alanyl-beta-naphthylamide and L-leucyl-beta-naphthylamide, and sensitivities of inhibition by chelators or amino acids. These results suggest that the multiple forms of membrane-bound neutral arylamidase found in five different human organs are organ-specific isoenzymes.", "contents": "Comparison of human membrane-bound neutral arylamidases from small intestine, lung, kidney, liver and placenta. Human membrane-bound neutral arylamidases were solubilized from small intestinal mucosa, lung, kidney, liver and placenta with trypsin. These five membrane-bound neutral arylamidases were identified by polyacrylamide gel-disc electrophoresis. The heat sensitivity of each enzyme was in the order, liver and placenta greater than kidney greater than lung greater than small intestine. This order correlates with that of electrophoretic mobility, except for the placental membrane-bound neutral arylamidase. Five membrane-bound neutral arylamidases have the same molecular weight, 240 000, as estimated by Sephadex G-200 gel filtration. The five membrane-bound neutral arylamidase have very similar KM values (8.7 x 10(-5) M towards L-alanyl-beta-naphthylamide), optimal pH values, hydrolysis ratios towards L-alanyl-beta-naphthylamide and L-leucyl-beta-naphthylamide, and sensitivities of inhibition by chelators or amino acids. These results suggest that the multiple forms of membrane-bound neutral arylamidase found in five different human organs are organ-specific isoenzymes."}
{"id": "PMID:16711", "title": "Anti-tumour immunity by normal allogeneic blood transfusion in rat.", "content": "Growth of transplantable KMT-17 tumour in syngeneic WKA/MK rats was inhibited by i.v. preimmunization with whole blood from normal rats of allogeneic strains. The inhibitory effect was also observed in rats immunized with allogeneic white blood cells alone. The strength of the inhibitory effect mainly depended on the the strain of donor rat used; blood from Donryu and Kyoto strain rats produced the strongest inhibition, blood from Tokyo and Fischer strain rats produced moderate inhibition to the syngeneic tumour growth. Blood from ACI/N strain rats did not produce the inhibition. The mechanism of blood transfusion in inhibiting tumour growth is not yet clear. However, it seems that GVH reaction does not play an important role in the mechanism of the inhibition effect, because the effect was obtained by immunization with mitomycin C-treated allogeneic white blood cells and also by the immunization effect may be due to nonspecific active immunization. Significance of blood transfusion with special reference to clinical immunogtherapy of cancer is discussed.", "contents": "Anti-tumour immunity by normal allogeneic blood transfusion in rat. Growth of transplantable KMT-17 tumour in syngeneic WKA/MK rats was inhibited by i.v. preimmunization with whole blood from normal rats of allogeneic strains. The inhibitory effect was also observed in rats immunized with allogeneic white blood cells alone. The strength of the inhibitory effect mainly depended on the the strain of donor rat used; blood from Donryu and Kyoto strain rats produced the strongest inhibition, blood from Tokyo and Fischer strain rats produced moderate inhibition to the syngeneic tumour growth. Blood from ACI/N strain rats did not produce the inhibition. The mechanism of blood transfusion in inhibiting tumour growth is not yet clear. However, it seems that GVH reaction does not play an important role in the mechanism of the inhibition effect, because the effect was obtained by immunization with mitomycin C-treated allogeneic white blood cells and also by the immunization effect may be due to nonspecific active immunization. Significance of blood transfusion with special reference to clinical immunogtherapy of cancer is discussed."}
{"id": "PMID:16712", "title": "The immune reponse to type III pneumococcal polysaccharide in mice with malaria.", "content": "The immune response of BALB/c mice to type III pneumococcal polysaccharide (SIII), as measured by splenic PFC, was abolished at the height of an acute self-limiting attack of malaria caused by the murine plasmodium P. yoelii, over a wide range of antigen doses. The response to antigen, given at various times after clinical recovery, gradually reappeared, but did not reach normal levels until 12 weeks after the injection of the parasite. A second injection of P. yoelii given 1 hr before SIII caused a moderate degree of depression, although in this case the plasmodium does not multiply. In chronic malaria the response to SIII was also very poor. Short term under-nourishment was found to reduce only slightly the response to SIII.", "contents": "The immune reponse to type III pneumococcal polysaccharide in mice with malaria. The immune response of BALB/c mice to type III pneumococcal polysaccharide (SIII), as measured by splenic PFC, was abolished at the height of an acute self-limiting attack of malaria caused by the murine plasmodium P. yoelii, over a wide range of antigen doses. The response to antigen, given at various times after clinical recovery, gradually reappeared, but did not reach normal levels until 12 weeks after the injection of the parasite. A second injection of P. yoelii given 1 hr before SIII caused a moderate degree of depression, although in this case the plasmodium does not multiply. In chronic malaria the response to SIII was also very poor. Short term under-nourishment was found to reduce only slightly the response to SIII."}
{"id": "PMID:16716", "title": "Beta-2 adrenoceptor blocking activity of penbutolol and propranolol at very low doses.", "content": "The relative potency of penbutolol, a new beta adrenergic receptor blocking agent, was compared with propranolol by a four-point assay on healthy male subjects. A dose-response relationship to intravenous doses of propranolol in the microgram range was obtained during a steady state of infusion of epinephrine. Two subjects underwent the entire assay according to the Latin square design and four others each underwent one schedule of design on different days. The potency of penbutolol thus assessed was consistent with reported results. This study emphasizes the importance of intersubject variation and differential receptor sensitivity in individuals. The use of epinephrine as a beta receptor adrenergic agonist for evaluation of selective beta adrenergic receptor blocking activities is discussed.", "contents": "Beta-2 adrenoceptor blocking activity of penbutolol and propranolol at very low doses. The relative potency of penbutolol, a new beta adrenergic receptor blocking agent, was compared with propranolol by a four-point assay on healthy male subjects. A dose-response relationship to intravenous doses of propranolol in the microgram range was obtained during a steady state of infusion of epinephrine. Two subjects underwent the entire assay according to the Latin square design and four others each underwent one schedule of design on different days. The potency of penbutolol thus assessed was consistent with reported results. This study emphasizes the importance of intersubject variation and differential receptor sensitivity in individuals. The use of epinephrine as a beta receptor adrenergic agonist for evaluation of selective beta adrenergic receptor blocking activities is discussed."}
{"id": "PMID:16717", "title": "Cardiovascular effects of total hip placement in man. With observations on the effects of methylmethacrylate on the isolated rabbit heart.", "content": "The cardiovascular effects of total hip placement were evaluated in 10 surgical patients, aged 55 to 82, while receiving fluroxene-N2O-O2 anesthesia. The anesthetic regimen caused mild cardiovascular depression. The placement of the acrylic cement into the acetabulum and femoral shaft also induced mild cardiovascular depression, but these changes were not significant at p less than 0.05. In one 67-yr-old woman, there were significant reductions of cardiac output and stroke volume 2 min after the insertion of acrylic into the femoral shaft, despite careful replacement of intravascular loss and careful anesthetic management. Methylmethacrylate (1 X 10(-6) to 1 X 10(-4), v/v) was administered to 24 isolated perfused rabbits hearts. These concentrations of methylmetacrylate are of the same order as measurable blood levels in surgical patients. There was a dose-dependent depression of left ventricular dP/dt correlated with a depression of the spontaneous heart rate. When the bradycardia was prevented by electrically pacing the hearts or the administration of atropine, the depressed dP/dt rose to control levels. Reduction in myocardial temperature and heart rate by means of reduction in perfusate temperature of the isolated hearts reduced the myocardial depressant effect of methylmethacrylate.", "contents": "Cardiovascular effects of total hip placement in man. With observations on the effects of methylmethacrylate on the isolated rabbit heart. The cardiovascular effects of total hip placement were evaluated in 10 surgical patients, aged 55 to 82, while receiving fluroxene-N2O-O2 anesthesia. The anesthetic regimen caused mild cardiovascular depression. The placement of the acrylic cement into the acetabulum and femoral shaft also induced mild cardiovascular depression, but these changes were not significant at p less than 0.05. In one 67-yr-old woman, there were significant reductions of cardiac output and stroke volume 2 min after the insertion of acrylic into the femoral shaft, despite careful replacement of intravascular loss and careful anesthetic management. Methylmethacrylate (1 X 10(-6) to 1 X 10(-4), v/v) was administered to 24 isolated perfused rabbits hearts. These concentrations of methylmetacrylate are of the same order as measurable blood levels in surgical patients. There was a dose-dependent depression of left ventricular dP/dt correlated with a depression of the spontaneous heart rate. When the bradycardia was prevented by electrically pacing the hearts or the administration of atropine, the depressed dP/dt rose to control levels. Reduction in myocardial temperature and heart rate by means of reduction in perfusate temperature of the isolated hearts reduced the myocardial depressant effect of methylmethacrylate."}
{"id": "PMID:16718", "title": "Erythrocyte adenosine triphosphate and 2,3-diphosphoglycerate after human renal transplantation: dissociation from hypophosphataemia.", "content": "1. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were determined in normal individuals, uraemic patients on chronic haemodialysis and patients who underwent renal transplantation, and correlated with plasma phosphate and arterial blood pH. 2. Significant increases in the 2,3-DPG and ATP content were found in the uraemic patients and these persisted after transplantation in spite of marked hypophosphataemia. 3. No correlation was established with plasma phosphate for either of the compounds but 2,3-DPG had a significant correlation with arterial blood pH. 4. Normal values for ATP and 2,3-DPG were observed in post-transplant patients with normal haematological values. The high amounts of erythrocyte 2,3-DPG and ATP in the early post-transplant period are independent of the circulating concentration of inorganic phosphate, and might represent the response of erythrocyte glycolysis to changing arterial blood pH.", "contents": "Erythrocyte adenosine triphosphate and 2,3-diphosphoglycerate after human renal transplantation: dissociation from hypophosphataemia. 1. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were determined in normal individuals, uraemic patients on chronic haemodialysis and patients who underwent renal transplantation, and correlated with plasma phosphate and arterial blood pH. 2. Significant increases in the 2,3-DPG and ATP content were found in the uraemic patients and these persisted after transplantation in spite of marked hypophosphataemia. 3. No correlation was established with plasma phosphate for either of the compounds but 2,3-DPG had a significant correlation with arterial blood pH. 4. Normal values for ATP and 2,3-DPG were observed in post-transplant patients with normal haematological values. The high amounts of erythrocyte 2,3-DPG and ATP in the early post-transplant period are independent of the circulating concentration of inorganic phosphate, and might represent the response of erythrocyte glycolysis to changing arterial blood pH."}
{"id": "PMID:16731", "title": "A study of the in vitro and in vivo interaction of barium sulphate particles with gastro-intestinal mucus.", "content": "The in vivo interaction of various radiopaques with mucus was investigated by a determination of the pH-mobility curves of the treated particles. It was found that mucus covered the radiopaque particles both in vivo and in vitro. This interaction was not affected by the nature of the radiopaque or by the state of the mucous membrane. The changed state of the mucus was modified by the diet of the rat from which it was derived. The results are discussed with reference to the technique used in the administration of radiopaques.", "contents": "A study of the in vitro and in vivo interaction of barium sulphate particles with gastro-intestinal mucus. The in vivo interaction of various radiopaques with mucus was investigated by a determination of the pH-mobility curves of the treated particles. It was found that mucus covered the radiopaque particles both in vivo and in vitro. This interaction was not affected by the nature of the radiopaque or by the state of the mucous membrane. The changed state of the mucus was modified by the diet of the rat from which it was derived. The results are discussed with reference to the technique used in the administration of radiopaques."}
{"id": "PMID:16732", "title": "In vitro efficacy of some drugs  on promastigotes of Leishmania donovani.", "content": "Sodium stibogluconate, metronidazole and dehydroemetine Roche were tested for their in vitro action on the mobility, morphology and survival of promastigotes of Leishmania donovani. At low concentrations, sodium stibogluconate, the drug of choice for kala azar treatment in Iraq proved to be poorly  effective in the prevention of promastigotes growth in vitro. On the other hand, both metronidazole and dehydroemetine Roche at low concentrations were highly effective in the prevention of promastigotes of L. donovani growth in vitro. 3.51 X 10(2), 9.34 and 3.13 mmol of sodium stibogluconate, metronidazole and dehydroemetine, respectively, were required to show the same effect in vitro.", "contents": "In vitro efficacy of some drugs  on promastigotes of Leishmania donovani. Sodium stibogluconate, metronidazole and dehydroemetine Roche were tested for their in vitro action on the mobility, morphology and survival of promastigotes of Leishmania donovani. At low concentrations, sodium stibogluconate, the drug of choice for kala azar treatment in Iraq proved to be poorly  effective in the prevention of promastigotes growth in vitro. On the other hand, both metronidazole and dehydroemetine Roche at low concentrations were highly effective in the prevention of promastigotes of L. donovani growth in vitro. 3.51 X 10(2), 9.34 and 3.13 mmol of sodium stibogluconate, metronidazole and dehydroemetine, respectively, were required to show the same effect in vitro."}
{"id": "PMID:16733", "title": "[The influence of surgery on serum enzyme changes].", "content": "Gamma-GT, which appears as a sensitive indicator in the enzyme pattern during postoperative examination, is especially recommended (besides the GOT and GPT enzymes) in detecting and watching the course of hepatocellular lesions. Distinction between parenchymatous and obstructive icterus can in some cases be made at an early stage by comparison with AP. Distinction between increases in biliary and ossal AP activity is possible with the help of Gamma-GT. Where liver metastases are suspected clinically, increased Gamma-GT activity makes metastization into the liver appear likely.", "contents": "[The influence of surgery on serum enzyme changes]. Gamma-GT, which appears as a sensitive indicator in the enzyme pattern during postoperative examination, is especially recommended (besides the GOT and GPT enzymes) in detecting and watching the course of hepatocellular lesions. Distinction between parenchymatous and obstructive icterus can in some cases be made at an early stage by comparison with AP. Distinction between increases in biliary and ossal AP activity is possible with the help of Gamma-GT. Where liver metastases are suspected clinically, increased Gamma-GT activity makes metastization into the liver appear likely."}
{"id": "PMID:16729", "title": "Spontaneous variability of the hemoglobin affinity for oxygen.", "content": "In order to evaluate the accuracy of our method of P50 determination, we measured P50 and 2,3-DPG on different days on several members of our laboratory staff and were surprised to find significant variation. Initially, we indicted our methodology but subsequent data suggest that significant P50 variability occurs, not correlated to alterations in 2,3-DPG or red cell pH. The largest variability on different days. 8.5 torr, occurred in a laboratory staff member studied 7 days apart. The P50 determinations were made by fixing PO2 by tonometry and determining oxyhemoglobin saturation by Van Slyke analysis. In contrast to our in vivo data, serial studies over 5-20 days performed upon 3 samples of stored CPD bank blood demonstrated the expected progressive decline in both 2,3-DPG and P50.", "contents": "Spontaneous variability of the hemoglobin affinity for oxygen. In order to evaluate the accuracy of our method of P50 determination, we measured P50 and 2,3-DPG on different days on several members of our laboratory staff and were surprised to find significant variation. Initially, we indicted our methodology but subsequent data suggest that significant P50 variability occurs, not correlated to alterations in 2,3-DPG or red cell pH. The largest variability on different days. 8.5 torr, occurred in a laboratory staff member studied 7 days apart. The P50 determinations were made by fixing PO2 by tonometry and determining oxyhemoglobin saturation by Van Slyke analysis. In contrast to our in vivo data, serial studies over 5-20 days performed upon 3 samples of stored CPD bank blood demonstrated the expected progressive decline in both 2,3-DPG and P50."}
{"id": "PMID:16734", "title": "Tardive dyskinesia: relationship with a primary affective disorder.", "content": "We reviewed all Mayo Clinic case histories in which a diagnosis of tardive dyskinesia or dyskinesia might have been recorded during the years 1965 through 1973  and interviewed 18 consecutive patients in the Department of Psychiatry and Psychology. Among the histories and patients, we found a high incidence of primary affective disorders. Four of the five  men had a history of chronic alcohol abuse and symptoms of depression. We recommend that people who have primary affective disorders and chronic alcohol abuse with depression should be given antipsychotic medication, stimulants, or diazepam only after extremely careful consideration.", "contents": "Tardive dyskinesia: relationship with a primary affective disorder. We reviewed all Mayo Clinic case histories in which a diagnosis of tardive dyskinesia or dyskinesia might have been recorded during the years 1965 through 1973  and interviewed 18 consecutive patients in the Department of Psychiatry and Psychology. Among the histories and patients, we found a high incidence of primary affective disorders. Four of the five  men had a history of chronic alcohol abuse and symptoms of depression. We recommend that people who have primary affective disorders and chronic alcohol abuse with depression should be given antipsychotic medication, stimulants, or diazepam only after extremely careful consideration."}
{"id": "PMID:16730", "title": "Oxygen availability during hypothermic cardiopulmonary bypass.", "content": "Oxygen availability during cardiopulmonary bypass was assessed in 22 patients under hypothermic and relatively normothermic conditions. The patients were divided into two groups, 17 of whom received ACD blood and 5, CPD blood. The mean P50 for all patients fell from a preoperative value of 25.9 +/- 2.4 (SD) to 15.6 +/- 2.1 during hypothermia confirming a leftward shift of the oxyhemoglobin dissociation curve. Oxygen uptake, calculated from a-v oxygen content differences (avDO2) and flow, was significantly lower during hypothermic bypass (65 +/- 27 ml/min) than during rewarming (121 +/- 41 ml/min). The increase in oxygen affinity during hypothermia was influenced also by changes in acid base and 2,3-DPG concentrations, the changes being similar in both the ACD and CPD groups of patients. During rewarming, however, oxygen availability was increased in the CPD group presumably from significantly increased 2,3-DPG concentrations. A \"functional\" value of hemoglobin, based upon the effects of the shift of the oxyhemoglobin dissociation curve and, therefore, reflecting the true capacity of hemoglobin to unload oxygen at the tissue level, was calculated. During the hypothermic phase of bypass, this functional hemoglobin was only 4.2 g/100 ml blood, suggesting that, in spite of reduced metabolic demands, oxygenation reserves are minimal.", "contents": "Oxygen availability during hypothermic cardiopulmonary bypass. Oxygen availability during cardiopulmonary bypass was assessed in 22 patients under hypothermic and relatively normothermic conditions. The patients were divided into two groups, 17 of whom received ACD blood and 5, CPD blood. The mean P50 for all patients fell from a preoperative value of 25.9 +/- 2.4 (SD) to 15.6 +/- 2.1 during hypothermia confirming a leftward shift of the oxyhemoglobin dissociation curve. Oxygen uptake, calculated from a-v oxygen content differences (avDO2) and flow, was significantly lower during hypothermic bypass (65 +/- 27 ml/min) than during rewarming (121 +/- 41 ml/min). The increase in oxygen affinity during hypothermia was influenced also by changes in acid base and 2,3-DPG concentrations, the changes being similar in both the ACD and CPD groups of patients. During rewarming, however, oxygen availability was increased in the CPD group presumably from significantly increased 2,3-DPG concentrations. A \"functional\" value of hemoglobin, based upon the effects of the shift of the oxyhemoglobin dissociation curve and, therefore, reflecting the true capacity of hemoglobin to unload oxygen at the tissue level, was calculated. During the hypothermic phase of bypass, this functional hemoglobin was only 4.2 g/100 ml blood, suggesting that, in spite of reduced metabolic demands, oxygenation reserves are minimal."}
{"id": "PMID:16735", "title": "Multi-clinic cross-over comparison of triazolam (Halcion) and placebo in the treatment of co-existing insomnia and anxiety in anxious out-patients.", "content": "In this multi-clinic double-blind cross-over designed study, forty-five anxious and insomniac out-patients received either triazolam (Halcion) 0.25 mg or placebo at bedtime. After seven days the medications were crossed over. The dosage was doubled after nights 2 and 9 if good sleep was not produced. Three patients dropped out, two on placebo (one for side effects and one for lack of efficacy) and one on triazolam (due to misunderstanding instructions). Analysis of sleep questionnaire data showed superiority of triazolam to placebo (p less .001) in all parameters. The incidence of dreams was not affected. Analysis of antianxiety efficacy showed that triazolam was superior to placebo (p less than .001) in all parameters, both physician's and self ratings. Thus, either triazolam or a good night's sleep significantly relieved the patient's anxiety. No side effects or abnormal laboratory values of significance were attributable to triazolam.", "contents": "Multi-clinic cross-over comparison of triazolam (Halcion) and placebo in the treatment of co-existing insomnia and anxiety in anxious out-patients. In this multi-clinic double-blind cross-over designed study, forty-five anxious and insomniac out-patients received either triazolam (Halcion) 0.25 mg or placebo at bedtime. After seven days the medications were crossed over. The dosage was doubled after nights 2 and 9 if good sleep was not produced. Three patients dropped out, two on placebo (one for side effects and one for lack of efficacy) and one on triazolam (due to misunderstanding instructions). Analysis of sleep questionnaire data showed superiority of triazolam to placebo (p less .001) in all parameters. The incidence of dreams was not affected. Analysis of antianxiety efficacy showed that triazolam was superior to placebo (p less than .001) in all parameters, both physician's and self ratings. Thus, either triazolam or a good night's sleep significantly relieved the patient's anxiety. No side effects or abnormal laboratory values of significance were attributable to triazolam."}
{"id": "PMID:16736", "title": "Interactions with antiepileptic drugs.", "content": "Most of the currently available antiepileptic drugs have a low therapeutic ratio and therefore a drug interaction causing elevation of the serum level of one of these compounds can readily lead to drug intoxication. Phenytoin, in particular, is vulnerable because its metabolism is dose-related and at therapeutic serum levels the enzyme system involved in its degradation is easily inhibited by concurrent drug administration. As multiple drug therapy has traditionally been practised in the management of epilepsy, clinically important interactions are common. Furthermore, most of the drugs used in the treatment of major epilepsies are potent inducers of hepatic microsomal enzymes and can therefore stimulate the metabolism of concurrently-administered drugs to such an extent that they may be rendered ineffective. The use of one drug alone is recommended, where possible, in the management of epilepsy.", "contents": "Interactions with antiepileptic drugs. Most of the currently available antiepileptic drugs have a low therapeutic ratio and therefore a drug interaction causing elevation of the serum level of one of these compounds can readily lead to drug intoxication. Phenytoin, in particular, is vulnerable because its metabolism is dose-related and at therapeutic serum levels the enzyme system involved in its degradation is easily inhibited by concurrent drug administration. As multiple drug therapy has traditionally been practised in the management of epilepsy, clinically important interactions are common. Furthermore, most of the drugs used in the treatment of major epilepsies are potent inducers of hepatic microsomal enzymes and can therefore stimulate the metabolism of concurrently-administered drugs to such an extent that they may be rendered ineffective. The use of one drug alone is recommended, where possible, in the management of epilepsy."}
{"id": "PMID:16740", "title": "[Sugar studies at Turku].", "content": "This survey concerns the essential findings in two clinical trials. The first study involved almost complete substitution of sucrose (S) by fructose (F) or xylitol (X). After 2 years the mean DMFS-increment was 7.2 in the S-group, 3.8 in the F-group, and 0.0 in the X-group. The second study comprised partial substitution, the effects of a S- or X-containing chewing gum being compared during 1 year. The subjects consumed 4.0 chewing gums per day in the S-group and correspondingly 4.5 in the X-group. In the S-group the caries incidence assessed independently by clinical and radiographical means was significantly higher than in the X-group. It is concluded that the metabolic studies indicate the relative safety of perorally administered xylitol at the present dosage levels. In view on the findings in the chewing gum study it is suggested that the non- and anti-cariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and the physico-chemical effects in plaque and saliva brought about through low and repeated dosage.", "contents": "[Sugar studies at Turku]. This survey concerns the essential findings in two clinical trials. The first study involved almost complete substitution of sucrose (S) by fructose (F) or xylitol (X). After 2 years the mean DMFS-increment was 7.2 in the S-group, 3.8 in the F-group, and 0.0 in the X-group. The second study comprised partial substitution, the effects of a S- or X-containing chewing gum being compared during 1 year. The subjects consumed 4.0 chewing gums per day in the S-group and correspondingly 4.5 in the X-group. In the S-group the caries incidence assessed independently by clinical and radiographical means was significantly higher than in the X-group. It is concluded that the metabolic studies indicate the relative safety of perorally administered xylitol at the present dosage levels. In view on the findings in the chewing gum study it is suggested that the non- and anti-cariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and the physico-chemical effects in plaque and saliva brought about through low and repeated dosage."}
{"id": "PMID:16742", "title": "The effects of dopamine on renin release in vitro.", "content": "To examine the direct effects of dopamine on renin release, the in vitro rat kidney slice system, devoid of hemodynamic and humoral effects, was chosen. In the presence of an antioxidant, ascorbic acid (6 X 10(-4)M), a significant dose-related stimulation of renin release was observed with addition of 10(-5)M and higher concentrations of dopamine. When the monoamine oxidase inhibitor, pheniprazine (1 X 10(-5)M) was added, significant, dose-related stimulation of renin release was observed with 10(-8)M and higher concentrations of dopamine. Dopamine-induced renin release was not inhibited by the presence of the alpha-adrenergic antagonist, phentolamine (9 X 10(-4)M), the dopaminergic antagonist, haloperidol (5 X 10(-5)M) or the neural uptake inhibitor, cocaine (1 X 10(-5)M). However, the presence of the beta-adrenergic antagonist, propranolol (2 X 10(-4)M) completely inhibited dopamine-induced renin release. These studies indicate that dopamine can directly stimulate renin release in the absence of effects of hemodynamic factors, alterations in sodium metabolism or release of endogenous adrenergic agents. Further, this direct effect of dopamine on renin release appears to be mediated by an agonistic effect on the juxtaglomerular beta receptor rather than by the presence of a specific dopaminergic receptor for renin release.", "contents": "The effects of dopamine on renin release in vitro. To examine the direct effects of dopamine on renin release, the in vitro rat kidney slice system, devoid of hemodynamic and humoral effects, was chosen. In the presence of an antioxidant, ascorbic acid (6 X 10(-4)M), a significant dose-related stimulation of renin release was observed with addition of 10(-5)M and higher concentrations of dopamine. When the monoamine oxidase inhibitor, pheniprazine (1 X 10(-5)M) was added, significant, dose-related stimulation of renin release was observed with 10(-8)M and higher concentrations of dopamine. Dopamine-induced renin release was not inhibited by the presence of the alpha-adrenergic antagonist, phentolamine (9 X 10(-4)M), the dopaminergic antagonist, haloperidol (5 X 10(-5)M) or the neural uptake inhibitor, cocaine (1 X 10(-5)M). However, the presence of the beta-adrenergic antagonist, propranolol (2 X 10(-4)M) completely inhibited dopamine-induced renin release. These studies indicate that dopamine can directly stimulate renin release in the absence of effects of hemodynamic factors, alterations in sodium metabolism or release of endogenous adrenergic agents. Further, this direct effect of dopamine on renin release appears to be mediated by an agonistic effect on the juxtaglomerular beta receptor rather than by the presence of a specific dopaminergic receptor for renin release."}
{"id": "PMID:16743", "title": "Diagnosis of bilateral abdominal cryptorchidism by laparoscopy.", "content": "The authors report a case of abdominal retention of both testes, where the exact diagnosis was made by laparoscopy. They suggest the usefulness of laparoscopy also in urology.", "contents": "Diagnosis of bilateral abdominal cryptorchidism by laparoscopy. The authors report a case of abdominal retention of both testes, where the exact diagnosis was made by laparoscopy. They suggest the usefulness of laparoscopy also in urology."}
{"id": "PMID:16744", "title": "An approach to the toxicology of combustion products of materials.", "content": "Physiological and behavioral (conditioned avoidance) responses of male Long-Evans rats were determined during exposure to combustion products produced on thermal degradation of three different polymeric materials. Arterial blood samples were obtained for determination of carboxyhemoglobin (COHb) and acid/base status. Material A produced a syndrome of carbon monoxide (CO)-induced anoxia, the severity of which was a function of the mass of material degraded. Material B produced grand mal seizures despite COHb levels of less than 10%. Material C produced metabolic acidosis and a mild degree of CO-induced anoxia. Loss of avoidance responses occurred at significantly lower COHb levels for materials B and C in comparison to CO alone. Using responses to COHb as a reference, it was possible to detect the presence of other toxicants present in combustion products. Compounds found in smoke in very low concentrations may have a high degree of biological activity and be responsible for impairment of survival responses. We have labeled these compounds \"limiting\" toxicants. They constitute a significant hazard, which is added to that of CO and anoxia.", "contents": "An approach to the toxicology of combustion products of materials. Physiological and behavioral (conditioned avoidance) responses of male Long-Evans rats were determined during exposure to combustion products produced on thermal degradation of three different polymeric materials. Arterial blood samples were obtained for determination of carboxyhemoglobin (COHb) and acid/base status. Material A produced a syndrome of carbon monoxide (CO)-induced anoxia, the severity of which was a function of the mass of material degraded. Material B produced grand mal seizures despite COHb levels of less than 10%. Material C produced metabolic acidosis and a mild degree of CO-induced anoxia. Loss of avoidance responses occurred at significantly lower COHb levels for materials B and C in comparison to CO alone. Using responses to COHb as a reference, it was possible to detect the presence of other toxicants present in combustion products. Compounds found in smoke in very low concentrations may have a high degree of biological activity and be responsible for impairment of survival responses. We have labeled these compounds \"limiting\" toxicants. They constitute a significant hazard, which is added to that of CO and anoxia."}
{"id": "PMID:16745", "title": "Development of hepatic acetyl coenzyme A carboxylase in hormone-treated chicks.", "content": "It has been suggested that the carbohydrate-rich diet of chicks after hatching is responsible for the emergence of hepatic enzymes involved in lipogenesis; the injection of glucose to newly hatched chicks gives rise to an appreciable elvation on the activities of acetyl coenzyme A carboxylase and fatty acid synthetase. The present study shows that during the first hours after hatching, there is a natural elevation of glycemia which parallels the increase in acetyl coenzyme A carboxylase activity. However, the administration of hormones which alter the blood glucose levels considerably (insulin, tolbutamide, glucagon and hydrocortisone) did not influence the enzyme activity. The administration of thyroxine, estradiol and cyclic AMP, was also without effect. These results do not support the theory that the increased amount of blood glucose is the natural effector of the induction acetyl coenzyme A carboxylase. They also show that different lipogenic enzymes are not regulated via the same 'operon' since thyroxine or glucagon which alter the level of some enzymes on this pathway did not modify that of the acetyl coenzyme A carboxylase.", "contents": "Development of hepatic acetyl coenzyme A carboxylase in hormone-treated chicks. It has been suggested that the carbohydrate-rich diet of chicks after hatching is responsible for the emergence of hepatic enzymes involved in lipogenesis; the injection of glucose to newly hatched chicks gives rise to an appreciable elvation on the activities of acetyl coenzyme A carboxylase and fatty acid synthetase. The present study shows that during the first hours after hatching, there is a natural elevation of glycemia which parallels the increase in acetyl coenzyme A carboxylase activity. However, the administration of hormones which alter the blood glucose levels considerably (insulin, tolbutamide, glucagon and hydrocortisone) did not influence the enzyme activity. The administration of thyroxine, estradiol and cyclic AMP, was also without effect. These results do not support the theory that the increased amount of blood glucose is the natural effector of the induction acetyl coenzyme A carboxylase. They also show that different lipogenic enzymes are not regulated via the same 'operon' since thyroxine or glucagon which alter the level of some enzymes on this pathway did not modify that of the acetyl coenzyme A carboxylase."}
{"id": "PMID:16747", "title": "The energy metabolism of the leukocyte. IX. Changes in the concentration of the coenzymes NAD, NADH, NADP, and NADPH in polymorphonuclear leukocytes during phagocytosis of Staphylococcus albus and due to the action of phospholipase C.", "content": "The determination of the coenzymes NAD+, NADH, NADP+ and NADPH, by the use of a method of enzymatic cycling, demonstrates that the enzymes responsible for the stimulations found during the phagocytosis of Staphylococcus albus are NADH and NADPH oxidase of human leukocytes and NADPH oxidase in the case of guinea pig leukocytes. The effects of serum, of the bacterial strain used and of phospholipase C are also discussed.", "contents": "The energy metabolism of the leukocyte. IX. Changes in the concentration of the coenzymes NAD, NADH, NADP, and NADPH in polymorphonuclear leukocytes during phagocytosis of Staphylococcus albus and due to the action of phospholipase C. The determination of the coenzymes NAD+, NADH, NADP+ and NADPH, by the use of a method of enzymatic cycling, demonstrates that the enzymes responsible for the stimulations found during the phagocytosis of Staphylococcus albus are NADH and NADPH oxidase of human leukocytes and NADPH oxidase in the case of guinea pig leukocytes. The effects of serum, of the bacterial strain used and of phospholipase C are also discussed."}
{"id": "PMID:16748", "title": "Tissue distribution and blood levels of gamma-glutamyl transferase in the horse.", "content": "In the horse, gamma-glutamyl transferase (GGT) was found to be mainly located in the kidneys, liver and pancreas. As renal lesions are followed by a urinary escape of enzyme, it can be assumed that if there are raised serum enzyme levels then the source will be chiefly from the liver and pancreas. In the blood, GGT can be measured either in plasma or serum. Its mean level in 58 horses was 12 U/L. This level was not affected by moderate dilution or slight haemolysis and its activity was only slightly decreased by storage at--30 degrees C. The relative hepatic specificity of this enzyme and its easy measurement make it a potentially very useful measure of liver dysfunction in the horse.", "contents": "Tissue distribution and blood levels of gamma-glutamyl transferase in the horse. In the horse, gamma-glutamyl transferase (GGT) was found to be mainly located in the kidneys, liver and pancreas. As renal lesions are followed by a urinary escape of enzyme, it can be assumed that if there are raised serum enzyme levels then the source will be chiefly from the liver and pancreas. In the blood, GGT can be measured either in plasma or serum. Its mean level in 58 horses was 12 U/L. This level was not affected by moderate dilution or slight haemolysis and its activity was only slightly decreased by storage at--30 degrees C. The relative hepatic specificity of this enzyme and its easy measurement make it a potentially very useful measure of liver dysfunction in the horse."}
{"id": "PMID:16750", "title": "An isolation procedure for the native alpha chain of bovine hemoglobin. A study of the functional properties of this chain and its hybrid with the human beta chain.", "content": "In this paper we present a procedure for the isolation of the native bovine alpha chain. The method is based on affinity chromatography. The results show that the ligand-binding properties of the bovine alpha chain are almost identical to those of the human alpha chain. The hybrid alphaB2 betaH2 prepared by mixing bovine alpha chains and human beta chains shows ligand binding properties similar to those of human hemoglobin and different from those of bovine hemoglobin.", "contents": "An isolation procedure for the native alpha chain of bovine hemoglobin. A study of the functional properties of this chain and its hybrid with the human beta chain. In this paper we present a procedure for the isolation of the native bovine alpha chain. The method is based on affinity chromatography. The results show that the ligand-binding properties of the bovine alpha chain are almost identical to those of the human alpha chain. The hybrid alphaB2 betaH2 prepared by mixing bovine alpha chains and human beta chains shows ligand binding properties similar to those of human hemoglobin and different from those of bovine hemoglobin."}
{"id": "PMID:16751", "title": "Uridine phosphorylase from Escherichia coli. Physical and chemical characterization.", "content": "Uridine phosphorylase from Escherichia coli has been purified to homogeneity. The enzyme was found to have a molecular weight of 176000 and to consist of 8 probably identical subunits with molecular weights of 22000. These numbers were determined from equilibrium centrifugations in the analytical ultracentrifuge, from dodecylsulphate gel electrophoresis and from amino acid analysis. Moreover the following physico-chemical constants were determined: s020,w = 8.2 x 10(-13) s, upsilon2 = 0.751 cm3/g, A1%280 (1 cm) = 6.73 and a specific activity of 183 units/mg towards uridine. The enzyme shows some activity towards deoxyuridine and thymidine. The activity is not impaired through substitution by bromo, fluoro or methyl groups in the 5-position of the uracil base, but no enzymatic activity is observed when cytosine base is used in the nucleoside substrate.", "contents": "Uridine phosphorylase from Escherichia coli. Physical and chemical characterization. Uridine phosphorylase from Escherichia coli has been purified to homogeneity. The enzyme was found to have a molecular weight of 176000 and to consist of 8 probably identical subunits with molecular weights of 22000. These numbers were determined from equilibrium centrifugations in the analytical ultracentrifuge, from dodecylsulphate gel electrophoresis and from amino acid analysis. Moreover the following physico-chemical constants were determined: s020,w = 8.2 x 10(-13) s, upsilon2 = 0.751 cm3/g, A1%280 (1 cm) = 6.73 and a specific activity of 183 units/mg towards uridine. The enzyme shows some activity towards deoxyuridine and thymidine. The activity is not impaired through substitution by bromo, fluoro or methyl groups in the 5-position of the uracil base, but no enzymatic activity is observed when cytosine base is used in the nucleoside substrate."}
{"id": "PMID:16752", "title": "The exchange reaction of peptides R-D-alanyl-D-alanine with D-[14C]alanine to R-D-alanyl-D-[14C]alanine and D-alanine, catalysed by the membranes of Streptococcus faecalis ATCC 9790.", "content": "Under alkaline conditions, the membrane-bound DD-carboxypeptidase of Streptococcus faecalis ATCC 9790 catalyses exchange reactions in which the X-L-R3-D-Ala moiety of peptides of the type X-L-R3-D-Ala-D-Ala is transferred to simple amino compounds such as D-alanine, glycine and glycyl-glycine. The enzyme system is unable, however, to catalyse complex reactions that would simulate the natural transpeptidation reaction.", "contents": "The exchange reaction of peptides R-D-alanyl-D-alanine with D-[14C]alanine to R-D-alanyl-D-[14C]alanine and D-alanine, catalysed by the membranes of Streptococcus faecalis ATCC 9790. Under alkaline conditions, the membrane-bound DD-carboxypeptidase of Streptococcus faecalis ATCC 9790 catalyses exchange reactions in which the X-L-R3-D-Ala moiety of peptides of the type X-L-R3-D-Ala-D-Ala is transferred to simple amino compounds such as D-alanine, glycine and glycyl-glycine. The enzyme system is unable, however, to catalyse complex reactions that would simulate the natural transpeptidation reaction."}
{"id": "PMID:16753", "title": "The phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. 3. 1H and 31P nuclear-magnetic-resonance studies on the phosphocarrier protein HPr; tyrosine titration and denaturation studies.", "content": "The phosphocarrier protein HPr has been investigated by proton nuclear magnetic resonance (NMR) at 270 MHz in order to evaluate structural properties of the whole molecule and its active site. The titration behaviour of the three tyrosines of the HPr protein was analysed by monitoring the chemical shifts of the aromatic proton resonances of these residues as a function of pH. It was found that the HPr protein contains a lot of slowly exchanging NH backbone protons which suggested a relatively rigid secondary structure of the protein molecule itself although it contains no disulfide bridges. The HPr protein shows a sharp reversible denaturation behaviour at alkaline pH values. Between pH 10.8 and 11.1 two C-2 proton resonance peaks for the single histidine residue could be observed together with abrupt changes in the aromatic and aliphatic absorption region of the HPr protein which are due to chemical exchange processes. The NMR spectrum of the HPr protein is only changed a little upon raising the temperature from 14 degrees C to 70 degrees C. At 76 degrees C all resonances in the spectrum broaden and almost disappear. This process is irreversible.", "contents": "The phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. 3. 1H and 31P nuclear-magnetic-resonance studies on the phosphocarrier protein HPr; tyrosine titration and denaturation studies. The phosphocarrier protein HPr has been investigated by proton nuclear magnetic resonance (NMR) at 270 MHz in order to evaluate structural properties of the whole molecule and its active site. The titration behaviour of the three tyrosines of the HPr protein was analysed by monitoring the chemical shifts of the aromatic proton resonances of these residues as a function of pH. It was found that the HPr protein contains a lot of slowly exchanging NH backbone protons which suggested a relatively rigid secondary structure of the protein molecule itself although it contains no disulfide bridges. The HPr protein shows a sharp reversible denaturation behaviour at alkaline pH values. Between pH 10.8 and 11.1 two C-2 proton resonance peaks for the single histidine residue could be observed together with abrupt changes in the aromatic and aliphatic absorption region of the HPr protein which are due to chemical exchange processes. The NMR spectrum of the HPr protein is only changed a little upon raising the temperature from 14 degrees C to 70 degrees C. At 76 degrees C all resonances in the spectrum broaden and almost disappear. This process is irreversible."}
{"id": "PMID:16755", "title": "Stability in vitro of methylproscillaridin.", "content": "The in vitro stability of methylproscillaridin has been compared with that of proscillaridin, the activities of the glycosides being assayed by the 86Rb-technique. After incubation in gastric juice at pH 1,2, and 3, the activity half life of each glycoside was proportional to pH and was approximately 0.25 h, 2.5 h, and 25 h, respectively. The inactivation rate in pure hydrochloric acid at pH 2 did not differ from that in gastric juice of the same pH. The glycosides were stable in bile and enteric juice. In faeces, methylproscillaridin was stable and proscillaridin was inactivated with a half life of 32 h. It is concluded that the difference in biological availability between the two glycosides cannot be explained by differences in gastrointestinal stability.", "contents": "Stability in vitro of methylproscillaridin. The in vitro stability of methylproscillaridin has been compared with that of proscillaridin, the activities of the glycosides being assayed by the 86Rb-technique. After incubation in gastric juice at pH 1,2, and 3, the activity half life of each glycoside was proportional to pH and was approximately 0.25 h, 2.5 h, and 25 h, respectively. The inactivation rate in pure hydrochloric acid at pH 2 did not differ from that in gastric juice of the same pH. The glycosides were stable in bile and enteric juice. In faeces, methylproscillaridin was stable and proscillaridin was inactivated with a half life of 32 h. It is concluded that the difference in biological availability between the two glycosides cannot be explained by differences in gastrointestinal stability."}
{"id": "PMID:16756", "title": "The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats.", "content": "LSD and BOL (0.125-0.5 mg/kg) were equipotent in increasing the in vivo tyrosine hydroxylation in the striatum as measured by the accumulation of DOPA after inhibition of neuronal decarboxylase. However, with 2--4 mg/kg doses, the maximum effect of BOL was larger than that of LSD. LSD and BOL antagonized the apomorphine-induced decrease of DOPA accumulation, without affecting the haloperidol-induced increase. LSD like apomorphine inhibited the increase of DOPA accumulation seen after reserpine, cerebral hemisection and after gamma-butyrolactone (GBL). The effect of apomorphine in rats given GBL was blocked by haloperidol, but not by BOL and promethazine, whereas that of LSD was inhibited by haloperidol, BOL, and promethazine. These findings suggest that LSD and BOL directly affect nigro-neostriatal dopamine neurons. LSD therefore appears to be a partial agonist and BOL a pure antagonist at dopamine autoreceptors. It is proposed in addition that LSD activates and BOL blocks 5-HT receptors that control DOPA formation.", "contents": "The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats. LSD and BOL (0.125-0.5 mg/kg) were equipotent in increasing the in vivo tyrosine hydroxylation in the striatum as measured by the accumulation of DOPA after inhibition of neuronal decarboxylase. However, with 2--4 mg/kg doses, the maximum effect of BOL was larger than that of LSD. LSD and BOL antagonized the apomorphine-induced decrease of DOPA accumulation, without affecting the haloperidol-induced increase. LSD like apomorphine inhibited the increase of DOPA accumulation seen after reserpine, cerebral hemisection and after gamma-butyrolactone (GBL). The effect of apomorphine in rats given GBL was blocked by haloperidol, but not by BOL and promethazine, whereas that of LSD was inhibited by haloperidol, BOL, and promethazine. These findings suggest that LSD and BOL directly affect nigro-neostriatal dopamine neurons. LSD therefore appears to be a partial agonist and BOL a pure antagonist at dopamine autoreceptors. It is proposed in addition that LSD activates and BOL blocks 5-HT receptors that control DOPA formation."}
{"id": "PMID:16757", "title": "Vascular beta-adrenoceptor stimulating properties of phenylephrine.", "content": "In pithed rats pretreated with propranolol changes occurred in the slopes of dose--pressor response curves to i.v. phenylephrine and noradrenaline but not to LD 3098, a pure alpha-adrenoceptor stimulant. In dogs, cats, and spontaneously hypertensive rats pretreated with an alpha-adrenoceptor blocker, i.v. phenylephrine induced vasodilatory responses which were antagonised by propranolol. These results indicate that phenylephrine, in addition to its known beta1-agonistic properties, stimulates the vascular beta2-adrenoceptors.", "contents": "Vascular beta-adrenoceptor stimulating properties of phenylephrine. In pithed rats pretreated with propranolol changes occurred in the slopes of dose--pressor response curves to i.v. phenylephrine and noradrenaline but not to LD 3098, a pure alpha-adrenoceptor stimulant. In dogs, cats, and spontaneously hypertensive rats pretreated with an alpha-adrenoceptor blocker, i.v. phenylephrine induced vasodilatory responses which were antagonised by propranolol. These results indicate that phenylephrine, in addition to its known beta1-agonistic properties, stimulates the vascular beta2-adrenoceptors."}
{"id": "PMID:16767", "title": "Subpopulations of T-lymphocytes in Peyer's patches: sensitivity to antilymphocyte serum and adult thymectomy.", "content": "Anti-lymphocyte (ALS) treatment or adult thymectomy of the donor have been shown to depress respectively the cell proliferation and the cytotoxicity in the graft-versus-host (GVH) reaction. A quantitative assay and the histological criteria of the GVH reaction have been used to demonstrate that all the known subpopulations of T-lymphocytes involved in the GVH reaction are present in the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat.", "contents": "Subpopulations of T-lymphocytes in Peyer's patches: sensitivity to antilymphocyte serum and adult thymectomy. Anti-lymphocyte (ALS) treatment or adult thymectomy of the donor have been shown to depress respectively the cell proliferation and the cytotoxicity in the graft-versus-host (GVH) reaction. A quantitative assay and the histological criteria of the GVH reaction have been used to demonstrate that all the known subpopulations of T-lymphocytes involved in the GVH reaction are present in the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat."}
{"id": "PMID:16769", "title": "Correlation between serum dopamine-beta-hydroxylase activity and dopamine-beta-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands.", "content": "Serum dopamine-beta-hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine-beta-hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14-16 weeks of age, a negative correlation with dopamine-beta-hydroxylase activity in locus coeruleus at 3 weeks and 14-16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14-16 weeks of age.", "contents": "Correlation between serum dopamine-beta-hydroxylase activity and dopamine-beta-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands. Serum dopamine-beta-hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine-beta-hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14-16 weeks of age, a negative correlation with dopamine-beta-hydroxylase activity in locus coeruleus at 3 weeks and 14-16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14-16 weeks of age."}
{"id": "PMID:16776", "title": "Specific metabolic pathway in vitro of pinazepam and diazepam by liver microsomal enzymes of different animal species.", "content": "The metabolic pathway of Pinazepam and Diazepam in vitro was studied with rat, guinea pig and dog liver microsomes using a chromatographic and spectrophotometric technique. Two main pathways were observed, N1-dealkylation and C3-hydroxylation. N1-dealkylation was shown to be the predominant reaction for Pinazepam in all the animal species studied, while  C3-hydroxylation was the major metabolic pathway for Diazepam in the rat. No oxazepam was found when Pinazepam and Diazepam were incubated with liver microsomes.", "contents": "Specific metabolic pathway in vitro of pinazepam and diazepam by liver microsomal enzymes of different animal species. The metabolic pathway of Pinazepam and Diazepam in vitro was studied with rat, guinea pig and dog liver microsomes using a chromatographic and spectrophotometric technique. Two main pathways were observed, N1-dealkylation and C3-hydroxylation. N1-dealkylation was shown to be the predominant reaction for Pinazepam in all the animal species studied, while  C3-hydroxylation was the major metabolic pathway for Diazepam in the rat. No oxazepam was found when Pinazepam and Diazepam were incubated with liver microsomes."}
{"id": "PMID:16774", "title": "[Mechanism of the action of apressin under conditions of high temperature and physical exertion].", "content": "In experiments on rats subject to study were regularities governing the metabolism of glycogen, milk, pyruvic acid, phosphocreatine in the liver tissues, cortex, musculus gastrocnemius and in the myocardium, as well as of acids in the peripheral blood at 40 degrees C of outside temperature, 95 per cent humidity and during swimming. Investigations also covered preventive application of apressin in rats. The influence of stress was found to produce metabolic changes in the organism of rats. In hypoxia apressin tended to prolong the life-span of the test animals by as much as 30 per cent, to keep intact metabolism in the musculus gastrocnemius and in the myocardium, but, when used in a dose of 0.05 mg/kg, it failed to avert disorders in the cortex tissues.", "contents": "[Mechanism of the action of apressin under conditions of high temperature and physical exertion]. In experiments on rats subject to study were regularities governing the metabolism of glycogen, milk, pyruvic acid, phosphocreatine in the liver tissues, cortex, musculus gastrocnemius and in the myocardium, as well as of acids in the peripheral blood at 40 degrees C of outside temperature, 95 per cent humidity and during swimming. Investigations also covered preventive application of apressin in rats. The influence of stress was found to produce metabolic changes in the organism of rats. In hypoxia apressin tended to prolong the life-span of the test animals by as much as 30 per cent, to keep intact metabolism in the musculus gastrocnemius and in the myocardium, but, when used in a dose of 0.05 mg/kg, it failed to avert disorders in the cortex tissues."}
{"id": "PMID:16775", "title": "[Sulfaphenazole binding by p-450 cytochrome of liver microsomes of rats and its effect of cytochrome-p-450-reductase].", "content": "Tests set up \"in vitro\" on the rats' liver microsomes showed that sulfaphenazol, which in an inhibitor of the mixed type N-and O-demethylation, is bound as a substrate of the II type (aniline type). It attenuates spectral changes caused by aniline and vice versa. Sulfaphenazol inhibits the activity of the ADPH cytochrome-P-450-reductase.", "contents": "[Sulfaphenazole binding by p-450 cytochrome of liver microsomes of rats and its effect of cytochrome-p-450-reductase]. Tests set up \"in vitro\" on the rats' liver microsomes showed that sulfaphenazol, which in an inhibitor of the mixed type N-and O-demethylation, is bound as a substrate of the II type (aniline type). It attenuates spectral changes caused by aniline and vice versa. Sulfaphenazol inhibits the activity of the ADPH cytochrome-P-450-reductase."}
{"id": "PMID:16782", "title": "Regulation of gastric acid secretion.", "content": "The advent of the H2-histamine-receptor antagonists has given new life to the old hypothesis that histamine might be the final common chemical mediator of acid secretion. The available evidence, however, does not prove this hypothesis but does confer on histamine a role in the regulation of acid secretion in normal physiology. Evidence is mounting that, in addition to its stimulatory action, the vagus may play an inhibitory role in acid secretion and gastrin release. Our concepts of the gastric phase of acid secretion have been extended by the discovery of cross distension reflexes in the stomach: the pyloro-oxyntic reflex for acid secretion and the oxyntopyloric reflex for gastrin release. In addition, digested protein has been shown to stimulate directly the oxyntic gland mucosa, but the evidence is against a role for this mechanism in the intact stomach. The hormone(s) responsible for the intestinal phase have not been isolated but the physiological characteristics of entero-oxyntin (a nongastrin, enteric substance that acts on the oxyntic cell) have been defined. Gastric inhibitory polypeptide is an excellent candidate for the entero-gastrone released by fat, but whether it is the sole enterogastrone released is yet to be determined.", "contents": "Regulation of gastric acid secretion. The advent of the H2-histamine-receptor antagonists has given new life to the old hypothesis that histamine might be the final common chemical mediator of acid secretion. The available evidence, however, does not prove this hypothesis but does confer on histamine a role in the regulation of acid secretion in normal physiology. Evidence is mounting that, in addition to its stimulatory action, the vagus may play an inhibitory role in acid secretion and gastrin release. Our concepts of the gastric phase of acid secretion have been extended by the discovery of cross distension reflexes in the stomach: the pyloro-oxyntic reflex for acid secretion and the oxyntopyloric reflex for gastrin release. In addition, digested protein has been shown to stimulate directly the oxyntic gland mucosa, but the evidence is against a role for this mechanism in the intact stomach. The hormone(s) responsible for the intestinal phase have not been isolated but the physiological characteristics of entero-oxyntin (a nongastrin, enteric substance that acts on the oxyntic cell) have been defined. Gastric inhibitory polypeptide is an excellent candidate for the entero-gastrone released by fat, but whether it is the sole enterogastrone released is yet to be determined."}
{"id": "PMID:16783", "title": "Localization of hypophysiotropic neurohormones by assay of sections from various brain areas.", "content": "The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area.", "contents": "Localization of hypophysiotropic neurohormones by assay of sections from various brain areas. The results of studies of the localization of the hypothalamic hypophysiotropic factors based on their direct determination in sections or nuclear punches are described. Luteinizing hormone-releasing hormone was found in high concentrations in the median eminence-arcuate nucleus complex, in lower concentrations in the mediobasal zone of the preoptic area. In addition to these hypothalamic sites, it is present in all four periventricular organs, especially in the organum vasculosum laminae terminalis. Thyrotropin releasing hormone has a widespread distribution. High concentrations are in the median eminence, arcuate nucleus, dorsomedial nucleus, and anterior part of the ventromedial nucleus. Lower concentrations are in several other structures of the hypothalamus, preoptic area and septum, and low but measurable quantities are found in most of the structures of the brain. Somatostatin is also present in most structures of the central nervous system, with highest concentrations in the median eminence, arcuate nucleus, ventromedial nucleus and periventricular nucleus. There are indications that the ventromedial nucleus or its immediate vicinity contains growth hormone releasing factor. Prolactin releasing activity was present in the median eminence and mediobasal parts of the anterior hypothalamus, whereas prolactin inhibitory activity was in the dorsolateral parts of the anterior hypothalamus and/or preoptic area."}
{"id": "PMID:16787", "title": "Lysis of periadnexal adhesions for correction of infertility.", "content": "A series of patients is presented in whom lysis of periadnexal adhesions was carried out for correction of infertility. These 35 couples had been infertile for at least 1 year prior to surgery. Seventy-seven per cent had been trying to conceive for more than 18 months. Following diagnostic evaluation, periadnexal adhesions were found to be the sole cause of infertility in 83% of cases. Subsequent to surgery, 63% of the patients conceived, 82% within 18 months, and 57% gave birth to at least one viable child. There can be no doubt that periadnexal adhesions represent true pathology. Although often seemingly insignificant in character, at the macroscopic level, they appear to play a major role at the microscopic level in impairing ovum pickup by the fallopian tube. Gynecologists should recognize the importance of these structures as mediators of a condition of relative sterility. Thus, despite the demonstration of tubal patency, the function of the rather delicate fimbria may be compromised by periadnexal adhesions, conglutinations, and hydatids so that only a fraction of those eggs that leave the ovary at ovulation reach the interior of the fallopian tube.", "contents": "Lysis of periadnexal adhesions for correction of infertility. A series of patients is presented in whom lysis of periadnexal adhesions was carried out for correction of infertility. These 35 couples had been infertile for at least 1 year prior to surgery. Seventy-seven per cent had been trying to conceive for more than 18 months. Following diagnostic evaluation, periadnexal adhesions were found to be the sole cause of infertility in 83% of cases. Subsequent to surgery, 63% of the patients conceived, 82% within 18 months, and 57% gave birth to at least one viable child. There can be no doubt that periadnexal adhesions represent true pathology. Although often seemingly insignificant in character, at the macroscopic level, they appear to play a major role at the microscopic level in impairing ovum pickup by the fallopian tube. Gynecologists should recognize the importance of these structures as mediators of a condition of relative sterility. Thus, despite the demonstration of tubal patency, the function of the rather delicate fimbria may be compromised by periadnexal adhesions, conglutinations, and hydatids so that only a fraction of those eggs that leave the ovary at ovulation reach the interior of the fallopian tube."}
{"id": "PMID:16791", "title": "Double-blind placebo-controlled efficacy study of ketazolam (U-28,774).", "content": "The safety and efficacy of ketazolam (15 mg capsules) was compared to placebo in seventy-nine out-patients suffering from psychoneurotic anxiety, moderate or worse in severity. A flexible dosage range of 15-75 mg was used in this double-blind study lasting twenty-eight days. The average optimum therapeutic dose of ketazolam was 46-9 mg administered as a once-day dose at bedtime. Ketazolam was found to be significantly better than placebo in alleviating anxiety and its concomitant symptomatology as measured by the Hamilton Anxiety Rating Scale, three Physician's Global Impressions, two Patient's Global Impressions, and three Target Symptoms. Fifteen patients dropped from the placebo group before completion of the study, and two withdrew from the ketazolam group. The patients receiving ketazolam experienced a greater reduction in symptomatology throughout the study when compared to the placebo group. Side-effects experienced by the ketazolam patients were less than, or equal to, the placebo patients. No deleterious side-effects occurred. No differences between the two groups were found for vital signs, EKG's, laboratory tests, or physical examinations.", "contents": "Double-blind placebo-controlled efficacy study of ketazolam (U-28,774). The safety and efficacy of ketazolam (15 mg capsules) was compared to placebo in seventy-nine out-patients suffering from psychoneurotic anxiety, moderate or worse in severity. A flexible dosage range of 15-75 mg was used in this double-blind study lasting twenty-eight days. The average optimum therapeutic dose of ketazolam was 46-9 mg administered as a once-day dose at bedtime. Ketazolam was found to be significantly better than placebo in alleviating anxiety and its concomitant symptomatology as measured by the Hamilton Anxiety Rating Scale, three Physician's Global Impressions, two Patient's Global Impressions, and three Target Symptoms. Fifteen patients dropped from the placebo group before completion of the study, and two withdrew from the ketazolam group. The patients receiving ketazolam experienced a greater reduction in symptomatology throughout the study when compared to the placebo group. Side-effects experienced by the ketazolam patients were less than, or equal to, the placebo patients. No deleterious side-effects occurred. No differences between the two groups were found for vital signs, EKG's, laboratory tests, or physical examinations."}
{"id": "PMID:16792", "title": "Hypnotic efficacy of triazolam and methyprylon ininsomniac in-patients.", "content": "The hypnotic effects of a new triazolobenzodiazepine, triazolam (Halcion) 0-5 mg and methyprylon 300 mg was compared in twenty oncologic in-patient volunteers with insomnia using the preference technique. On the first night of the two-night trial, or methyprylon was given on a double-blind basis and on the second night the patients received the alternate medication. Following each trial night the patients were interviewed in regard to their sleep. Of the seventeen patients who completed the study, eleven patients preferred triazolam, three preferred methyprylon and three had no preference (p=0-057). Analysis of the various sleep parameters showed that triazolam helped the patients sleep more than methyprylon (p=0-13), induced more rapid sleep onset (p=0-003), gave a longer duration of sleep (p=0-013). The treatment was considered a success if the patient went to sleep in thirty minutes or less and slept for at least six hours. Triazolam was more successful than methyprylon in this respect (p=0-012). There were no side-effects reported on either of the drugs.", "contents": "Hypnotic efficacy of triazolam and methyprylon ininsomniac in-patients. The hypnotic effects of a new triazolobenzodiazepine, triazolam (Halcion) 0-5 mg and methyprylon 300 mg was compared in twenty oncologic in-patient volunteers with insomnia using the preference technique. On the first night of the two-night trial, or methyprylon was given on a double-blind basis and on the second night the patients received the alternate medication. Following each trial night the patients were interviewed in regard to their sleep. Of the seventeen patients who completed the study, eleven patients preferred triazolam, three preferred methyprylon and three had no preference (p=0-057). Analysis of the various sleep parameters showed that triazolam helped the patients sleep more than methyprylon (p=0-13), induced more rapid sleep onset (p=0-003), gave a longer duration of sleep (p=0-013). The treatment was considered a success if the patient went to sleep in thirty minutes or less and slept for at least six hours. Triazolam was more successful than methyprylon in this respect (p=0-012). There were no side-effects reported on either of the drugs."}
{"id": "PMID:16793", "title": "Intermediate use of triazolam: a sleep laboratory study.", "content": "The present study was undertaken to evaluate the intermediate effects of triazolam 0-5 mg on the sleep of insomniac patients. The results showed that triazolam is effective in inducing and maintaining sleep without producing any major effects on sleep staging. Triazolam did not lead to significant subjective complaints or any deterioration in the physical condition of the patients. The effectiveness of traizolam did not vary over a two-week period.", "contents": "Intermediate use of triazolam: a sleep laboratory study. The present study was undertaken to evaluate the intermediate effects of triazolam 0-5 mg on the sleep of insomniac patients. The results showed that triazolam is effective in inducing and maintaining sleep without producing any major effects on sleep staging. Triazolam did not lead to significant subjective complaints or any deterioration in the physical condition of the patients. The effectiveness of traizolam did not vary over a two-week period."}
{"id": "PMID:16794", "title": "Psychometric assessment of the therapeutic efficiency of antidepressant agents.", "content": "A clinical trial of four weeks duration was conducted involving a total of thirty depressed patients, of both sexes, aged between twenty and thirty-four years. The total number of patients was divided into three groups of ten patients each. One group received amitriptyline, the second group was administered noxiptyline and the third group was given dibenzepine. All drugs were administered orally. Patients were submitted to psychometric testing before and after drug administration. The tests used included the 'Hamilton Rating Scale for depression', the 'Hildreth Feeling Scale' and the 'D Scale' and the 'Trail Making Test' for the evaluation of psychomotor retardation. It was concluded that the Hamilton Rating Scale was the most relatively sensitive test utilized in assessing the depressive state and its improvement. Amitriptyline was found to be mostly anxiolytic; noxiptyline controlled both depression and anxiety to approximately the same extent; and dibenzepine was found to be a mood-elevating drug with an energizing action.", "contents": "Psychometric assessment of the therapeutic efficiency of antidepressant agents. A clinical trial of four weeks duration was conducted involving a total of thirty depressed patients, of both sexes, aged between twenty and thirty-four years. The total number of patients was divided into three groups of ten patients each. One group received amitriptyline, the second group was administered noxiptyline and the third group was given dibenzepine. All drugs were administered orally. Patients were submitted to psychometric testing before and after drug administration. The tests used included the 'Hamilton Rating Scale for depression', the 'Hildreth Feeling Scale' and the 'D Scale' and the 'Trail Making Test' for the evaluation of psychomotor retardation. It was concluded that the Hamilton Rating Scale was the most relatively sensitive test utilized in assessing the depressive state and its improvement. Amitriptyline was found to be mostly anxiolytic; noxiptyline controlled both depression and anxiety to approximately the same extent; and dibenzepine was found to be a mood-elevating drug with an energizing action."}
{"id": "PMID:16795", "title": "Some aspects of the pharmacology of analgesia.", "content": "This paper makes comparisons of some of the pharmacological properties of the opiate analgesics and the tricyclic antidepressants in order to justify the clinical examination of the tricyclics as potential analgesic or proanalgesic agents in man. Preliminary animal data suggest that the tricyclic agent clomipramine (Anafranil, Geigy) will potentiate the effects of morphine, pentazocine and cyclazocine.", "contents": "Some aspects of the pharmacology of analgesia. This paper makes comparisons of some of the pharmacological properties of the opiate analgesics and the tricyclic antidepressants in order to justify the clinical examination of the tricyclics as potential analgesic or proanalgesic agents in man. Preliminary animal data suggest that the tricyclic agent clomipramine (Anafranil, Geigy) will potentiate the effects of morphine, pentazocine and cyclazocine."}
{"id": "PMID:16796", "title": "The use of psychotropic drugs in rheumatology.", "content": "The possible role of various psychotropic drugs in the management of rheumatic diseases is considered--tranquillizers, sedatives, tricyclic antidepressants and monoamine oxidase inhibitors. The dilemma of which anti-depressant for which patient is considered. The possible association between rheumatoid disease and disorders of the brain, brain-stem and autonomic nervous system is discussed. Psychotropic drugs may effect the disease itself as well as the patient's mood. The author is opposed, however, to the idea that rheumatoid arthritis may be regarded as a psychosomatic disease.", "contents": "The use of psychotropic drugs in rheumatology. The possible role of various psychotropic drugs in the management of rheumatic diseases is considered--tranquillizers, sedatives, tricyclic antidepressants and monoamine oxidase inhibitors. The dilemma of which anti-depressant for which patient is considered. The possible association between rheumatoid disease and disorders of the brain, brain-stem and autonomic nervous system is discussed. Psychotropic drugs may effect the disease itself as well as the patient's mood. The author is opposed, however, to the idea that rheumatoid arthritis may be regarded as a psychosomatic disease."}
{"id": "PMID:16797", "title": "The use of psychotropic drugs in a pain clinic.", "content": "The paper is based on experiences gained at a hospital pain clinic. Patients attending such a pain clinic can be divided into three categories: (1) Those with chronic organic lesions in whom the mental state was little affected. (2) Those with organic lesions who had mental changes which influenced their experience of the pain. (3) Patients who had primary mental changes in whom the complaint of pain was a symptom of their mental state. The importance of full history taking, ab initio, is stressed. Much can be learned from patients' ideas of causation and these should be considered. Phychiatric diagnoses should be reached positively and not by a process of exclusion. Distinction must be made between depression and normal sadness and it is important to establish the relationship between the onset of depression and the painful symptoms. When psychopathology is evident a variety of treatments are available. There is, however, a 'hard core' of patients who display no depression and little anxiety. In such cases the manipulative value of pain should be considered.", "contents": "The use of psychotropic drugs in a pain clinic. The paper is based on experiences gained at a hospital pain clinic. Patients attending such a pain clinic can be divided into three categories: (1) Those with chronic organic lesions in whom the mental state was little affected. (2) Those with organic lesions who had mental changes which influenced their experience of the pain. (3) Patients who had primary mental changes in whom the complaint of pain was a symptom of their mental state. The importance of full history taking, ab initio, is stressed. Much can be learned from patients' ideas of causation and these should be considered. Phychiatric diagnoses should be reached positively and not by a process of exclusion. Distinction must be made between depression and normal sadness and it is important to establish the relationship between the onset of depression and the painful symptoms. When psychopathology is evident a variety of treatments are available. There is, however, a 'hard core' of patients who display no depression and little anxiety. In such cases the manipulative value of pain should be considered."}
{"id": "PMID:16799", "title": "Nefopam HCl interaction study with eight other drugs.", "content": "A controlled clinical trial was undertaken to determine potential for drug interaction of nefopam HCl, a new analgesic, with eight other widely used compounds. Nefopam HCl was administered in combination with these drugs and placebo to forty-five healthy volunteer subjects in nine groups of five subjects each. Possible drug interactions were detected by the occurrence of side-effects and interference with bioavailability of the new analgesic, also by changes in vital signs or in various laboratory tests. Results indicated no statistically significant differences in these parameters between the nefopam HCl-placebo regimen and the other eight combinations. Despite this, there were substantial clinical differences in the intensity and incidence of side-effects with combinations of codeine, pentazocine and propoxyphene. These differences warrant further study. Serum nefopam HCl levels were significantly higher on Day 3 than on Day 1, indicating no defect in bioavailability due to drug interaction. Overall, results of this study support the feasibility of concomitant use of these eight drugs with nefopam HCl for short treatment periods.", "contents": "Nefopam HCl interaction study with eight other drugs. A controlled clinical trial was undertaken to determine potential for drug interaction of nefopam HCl, a new analgesic, with eight other widely used compounds. Nefopam HCl was administered in combination with these drugs and placebo to forty-five healthy volunteer subjects in nine groups of five subjects each. Possible drug interactions were detected by the occurrence of side-effects and interference with bioavailability of the new analgesic, also by changes in vital signs or in various laboratory tests. Results indicated no statistically significant differences in these parameters between the nefopam HCl-placebo regimen and the other eight combinations. Despite this, there were substantial clinical differences in the intensity and incidence of side-effects with combinations of codeine, pentazocine and propoxyphene. These differences warrant further study. Serum nefopam HCl levels were significantly higher on Day 3 than on Day 1, indicating no defect in bioavailability due to drug interaction. Overall, results of this study support the feasibility of concomitant use of these eight drugs with nefopam HCl for short treatment periods."}
{"id": "PMID:16800", "title": "A comparative study of antidepressants in the treatment of depressive states.", "content": "The effect of six antidepressants has been investigated in six groups of twenty patients suffering from depressive states. The over-all response of the six groups, as well as the response of the individual target symptoms of depression according to the Hamilton Rating Scale are reported.", "contents": "A comparative study of antidepressants in the treatment of depressive states. The effect of six antidepressants has been investigated in six groups of twenty patients suffering from depressive states. The over-all response of the six groups, as well as the response of the individual target symptoms of depression according to the Hamilton Rating Scale are reported."}
{"id": "PMID:16801", "title": "Preference studies of triazolam with standard hypnotics in out-patients with insomnia.", "content": "One hundred and four patients suffering from insomnia took part in four different two-night double-blind crossover trials of triazolam. In three separate studies, triazolam 0-5 mg was compared to placebo, flurazepam 30 mg and chloral hydrate 500 mg. Triazolam 0-5 mg was found to be preferred and to be superior to placebo, flurazepam and chloral hydrate in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to the other treatments on the following: How much did the medication help you sleep, onset of sleep, duration of sleep and number of awakenings. Additionally, triazolam was superior to chloral hydrate on the feeling in the morning parameter. In another comparison of triazolam 0-25 mg to flurazepan 15 mg, triazolam was not significantly better than flurazepam on any of the efficacy parameters except that the patients felt more alert the morning following triazolam that following flurazepam. On all efficacy endpoints, trends for all parameters favoured triazolam 0-25 mg over flurazepam 15 mg. Untoward side-effects in these four studies were minimal.", "contents": "Preference studies of triazolam with standard hypnotics in out-patients with insomnia. One hundred and four patients suffering from insomnia took part in four different two-night double-blind crossover trials of triazolam. In three separate studies, triazolam 0-5 mg was compared to placebo, flurazepam 30 mg and chloral hydrate 500 mg. Triazolam 0-5 mg was found to be preferred and to be superior to placebo, flurazepam and chloral hydrate in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to the other treatments on the following: How much did the medication help you sleep, onset of sleep, duration of sleep and number of awakenings. Additionally, triazolam was superior to chloral hydrate on the feeling in the morning parameter. In another comparison of triazolam 0-25 mg to flurazepan 15 mg, triazolam was not significantly better than flurazepam on any of the efficacy parameters except that the patients felt more alert the morning following triazolam that following flurazepam. On all efficacy endpoints, trends for all parameters favoured triazolam 0-25 mg over flurazepam 15 mg. Untoward side-effects in these four studies were minimal."}
{"id": "PMID:16803", "title": "The nocturnal intragastric pH in EEG sleep stages in peptic ulcer patients.", "content": "In 10 peptic ulcer patients, 5 duodenal ulcer and 5 gastric ulcer patients, the relation of nocturnal intragastric pH to EEG sleep stages was examined. The nocturnal intragastric pH was monitored by pH-measuring telemeter and sleep stages were recorded simultaneously by electroencephalography throughout the night. The EEG sleep stages were classified after the criteria of Dement and Kleitman. The average of intragastric pH level at each sleep stage was higher in gastric ulcer than the duodenal ulcer. The intragastric pH level became low as the patients' sleep advanced to deep stage. This tendency was more likely in duodenal ulcer patients than the gastric ulcer patients, which indicated that the cephalic phase might play an important role in the pathogenesis of hyperacidity in duodenal ulcer.", "contents": "The nocturnal intragastric pH in EEG sleep stages in peptic ulcer patients. In 10 peptic ulcer patients, 5 duodenal ulcer and 5 gastric ulcer patients, the relation of nocturnal intragastric pH to EEG sleep stages was examined. The nocturnal intragastric pH was monitored by pH-measuring telemeter and sleep stages were recorded simultaneously by electroencephalography throughout the night. The EEG sleep stages were classified after the criteria of Dement and Kleitman. The average of intragastric pH level at each sleep stage was higher in gastric ulcer than the duodenal ulcer. The intragastric pH level became low as the patients' sleep advanced to deep stage. This tendency was more likely in duodenal ulcer patients than the gastric ulcer patients, which indicated that the cephalic phase might play an important role in the pathogenesis of hyperacidity in duodenal ulcer."}
{"id": "PMID:16806", "title": "Comparison of an H2 receptor antagonist and a neutralizing antacid on postprandial acid delivery into the duodenum in patients with duodenal ulcer.", "content": "Measurement of the postprandial rate of acid delivery into the duodenum directly assessed the efficacy of two radically different acid-reducing therapies for duodenal ulcer disease. Cimetidine, 400 mg, with an ordinary solid meal decreased the 4-hr delivery of titratable acid and hydrogen ion into the duodenum by 63 and 86%, respectively (P less than 0.01 versus control). Liquid Maalox, 30 ml, 1 and 3 hr after an identical meal reduced 4-hr delivery of acid by 47 and 74%, respectively (P less than 0.01 versus control). During the study period, the H2 receptor antagonist effected a continuous reduction in gastric acidity and the delivery of acid into the duodenum. The liquid neutralizing antacid produced a more fluctuating decrease in these parameters. However, given in these dosages, the magnitude and duration of the acid-reducing effect were similar for both treatments.", "contents": "Comparison of an H2 receptor antagonist and a neutralizing antacid on postprandial acid delivery into the duodenum in patients with duodenal ulcer. Measurement of the postprandial rate of acid delivery into the duodenum directly assessed the efficacy of two radically different acid-reducing therapies for duodenal ulcer disease. Cimetidine, 400 mg, with an ordinary solid meal decreased the 4-hr delivery of titratable acid and hydrogen ion into the duodenum by 63 and 86%, respectively (P less than 0.01 versus control). Liquid Maalox, 30 ml, 1 and 3 hr after an identical meal reduced 4-hr delivery of acid by 47 and 74%, respectively (P less than 0.01 versus control). During the study period, the H2 receptor antagonist effected a continuous reduction in gastric acidity and the delivery of acid into the duodenum. The liquid neutralizing antacid produced a more fluctuating decrease in these parameters. However, given in these dosages, the magnitude and duration of the acid-reducing effect were similar for both treatments."}
{"id": "PMID:16807", "title": "Aspirin esterase of gastric mucosal origin.", "content": "The enzyme, aspirin esterase, which converts acetylsalicyclic acid to the less toxic salicyclic acid, was found to be present in gastric mucosal specimens obtained from surgically resected tissue. The enzyme was found to be stable to storage and active at two pH optima. Alcohol in the reaction mixture produced a net effect of slowing the rate of aspirin hydrolysis; this was attributable to a marked inhibitory effect on aspirin esterase activity which was not completely counteracted by the increased rate of spontaneous breakdown of aspirin by alcohol. Age, sex, or gastric disease state of the patient from whom the tissue was obtained, did not significantly alter the level of enzyme activity measured, nor were different levels obtained from body or antral mucosa. In patients with gastric ulcer, those with a previous history of regular aspirin consumption did not show significantly different levels from those without such a history. It is concluded that aspirin esterase activity of gastric mucosa is not alone a significant factor in any role acetylsalicyclic acid may play in the etiology and natural history of chronic peptic ulcer.", "contents": "Aspirin esterase of gastric mucosal origin. The enzyme, aspirin esterase, which converts acetylsalicyclic acid to the less toxic salicyclic acid, was found to be present in gastric mucosal specimens obtained from surgically resected tissue. The enzyme was found to be stable to storage and active at two pH optima. Alcohol in the reaction mixture produced a net effect of slowing the rate of aspirin hydrolysis; this was attributable to a marked inhibitory effect on aspirin esterase activity which was not completely counteracted by the increased rate of spontaneous breakdown of aspirin by alcohol. Age, sex, or gastric disease state of the patient from whom the tissue was obtained, did not significantly alter the level of enzyme activity measured, nor were different levels obtained from body or antral mucosa. In patients with gastric ulcer, those with a previous history of regular aspirin consumption did not show significantly different levels from those without such a history. It is concluded that aspirin esterase activity of gastric mucosa is not alone a significant factor in any role acetylsalicyclic acid may play in the etiology and natural history of chronic peptic ulcer."}
{"id": "PMID:16812", "title": "Ditazole and platelets. I. Effect of ditazole on human platelet function in vitro.", "content": "Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) has been  shown to be a strong in vitro inhibitor of human platelet aggregation brought about by release reaction inducers; in contrast, it did not significantly affect primary ADP-induced aggregation. Ditazole strongly inhibited the release of platelet-bound 14C-serotonin under the influence of Thrombofax, whereas it did not interfere with the transport and storage of serotonin in nonstimulated platelets. The effect of ditazole was not potentiated by acetylsalicylic acid. Ditazole also inhibited ADP-reptilase clot retraction and modified thrombin-induced clot formation. The inhibition of platelet aggregation exerted by ditazole in plasma could be removed following gel filtration of platelets on Sepharose 2-B gel. This would indicate that ditazole does not act on platelets by a 'hit and run' mechanism.", "contents": "Ditazole and platelets. I. Effect of ditazole on human platelet function in vitro. Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) has been  shown to be a strong in vitro inhibitor of human platelet aggregation brought about by release reaction inducers; in contrast, it did not significantly affect primary ADP-induced aggregation. Ditazole strongly inhibited the release of platelet-bound 14C-serotonin under the influence of Thrombofax, whereas it did not interfere with the transport and storage of serotonin in nonstimulated platelets. The effect of ditazole was not potentiated by acetylsalicylic acid. Ditazole also inhibited ADP-reptilase clot retraction and modified thrombin-induced clot formation. The inhibition of platelet aggregation exerted by ditazole in plasma could be removed following gel filtration of platelets on Sepharose 2-B gel. This would indicate that ditazole does not act on platelets by a 'hit and run' mechanism."}
{"id": "PMID:16809", "title": "[Histamine 2 receptor antagonists in the treatment of gastric ulcer].", "content": "Eight patients with a clinical, radiology and endoscopic diagnosis of benign peptic ulcer were studied in a prospective fashion using Cimetidine (H2-Receptor antagonist). With this outgoing form of therapy the need for antiacid diminished greatly and pain totally disappeared. We discuss the possible etiological pathways of gastric ulcer and finally propose the simultaneous use of H2-Receptor antagonist and colesteramine with the goal of eliminating the two predominant factors that cause the lesion.", "contents": "[Histamine 2 receptor antagonists in the treatment of gastric ulcer]. Eight patients with a clinical, radiology and endoscopic diagnosis of benign peptic ulcer were studied in a prospective fashion using Cimetidine (H2-Receptor antagonist). With this outgoing form of therapy the need for antiacid diminished greatly and pain totally disappeared. We discuss the possible etiological pathways of gastric ulcer and finally propose the simultaneous use of H2-Receptor antagonist and colesteramine with the goal of eliminating the two predominant factors that cause the lesion."}
{"id": "PMID:16814", "title": "[Glucocorticoid action of beclomethasone and its propionate ester derivatives].", "content": "In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing efect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone.", "contents": "[Glucocorticoid action of beclomethasone and its propionate ester derivatives]. In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing efect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone."}
{"id": "PMID:16815", "title": "A comparative clinical study for the evaluation of antianxiety agents, (lorazepam, diazepam and placebo), in neurosis.", "content": "To evaluate the clinical effects of lorazepam on neurosis, a double-blind controlled trial by group comparison procedure was carried out using diazepam and placebo as control drugs. The clinical improvement and aggravation rates by means of a variety of assessment of change were compared between each of the two active drugs and placebo. The superiority, characteristics of therapeutic effects and minor side effects of lorazepam which is similar to those of diazepam, a standard benzodiazepine anxiolytic for the treatment of neurosis, were demonstrated. From this study, many important problems which might be influenced upon the outcome of the pharmacotherapy on neurotics, such as positive and negative placebo effects, aggravation and drop-out during the trial, were also evaluated.", "contents": "A comparative clinical study for the evaluation of antianxiety agents, (lorazepam, diazepam and placebo), in neurosis. To evaluate the clinical effects of lorazepam on neurosis, a double-blind controlled trial by group comparison procedure was carried out using diazepam and placebo as control drugs. The clinical improvement and aggravation rates by means of a variety of assessment of change were compared between each of the two active drugs and placebo. The superiority, characteristics of therapeutic effects and minor side effects of lorazepam which is similar to those of diazepam, a standard benzodiazepine anxiolytic for the treatment of neurosis, were demonstrated. From this study, many important problems which might be influenced upon the outcome of the pharmacotherapy on neurotics, such as positive and negative placebo effects, aggravation and drop-out during the trial, were also evaluated."}
{"id": "PMID:16816", "title": "[The regulation of FSH release by the testis. Studies on inhibin].", "content": "The FSH release from the hypophysis is suggested to be particularly regulated by a testicular hormone called inhibin. Origin, structure and target organs of inhibin are unknown. Experiments to test some hypotheses in this field are described. Adult male rats, prenatally treated with busulfan, show only Sertoli cells in the semiferous tubules. Experimental cryptorchidism and orchidectomy, however, leads to an increase in FSH levels as observed in normal animals. This indicates the role of Sertoli cells in FSH regulation. Ligation of efferent ducts of testes leads to an increase of FSH levels, too, indicating that an FSH-inhibiting principle cannot be absorbed. Interstitial testis fluid (ITF) of normal rats was applicated to immature female rats. Their FSH release is inhibited, visible in the lower ovarian weight gain following additional hCG-administration. Orchidectomized animals react with a decrease of FSH levels to the application of ITF. Therefore ITF seems to contain a FSH-inhibiting factor. Androgen binding protein-content of epididymes, however, is increased after repeated injections of ITF. It is concluded that testis (probably the Sertoli cells) produces a FSH-inhibiting factor, but ITF contains only small amounts of inhibin.", "contents": "[The regulation of FSH release by the testis. Studies on inhibin]. The FSH release from the hypophysis is suggested to be particularly regulated by a testicular hormone called inhibin. Origin, structure and target organs of inhibin are unknown. Experiments to test some hypotheses in this field are described. Adult male rats, prenatally treated with busulfan, show only Sertoli cells in the semiferous tubules. Experimental cryptorchidism and orchidectomy, however, leads to an increase in FSH levels as observed in normal animals. This indicates the role of Sertoli cells in FSH regulation. Ligation of efferent ducts of testes leads to an increase of FSH levels, too, indicating that an FSH-inhibiting principle cannot be absorbed. Interstitial testis fluid (ITF) of normal rats was applicated to immature female rats. Their FSH release is inhibited, visible in the lower ovarian weight gain following additional hCG-administration. Orchidectomized animals react with a decrease of FSH levels to the application of ITF. Therefore ITF seems to contain a FSH-inhibiting factor. Androgen binding protein-content of epididymes, however, is increased after repeated injections of ITF. It is concluded that testis (probably the Sertoli cells) produces a FSH-inhibiting factor, but ITF contains only small amounts of inhibin."}
{"id": "PMID:16818", "title": "Suppression of ACTH secretion by synthetic MSH-release inhibiting factor Pro-Leu-Gly-NH2 in Addison's disease.", "content": "The regulation of release of MSH and ACTH seems to be closely related. The effect of Pro-Leu-Gly-NH2, the most active MSH-release inhibiting factor (MIF), was investigated on ACTH-hypersecretion in six patients suffering from primary adrenocortical insufficiency. MIF was infused at constant rates with stepwise increase in concentration (0.25 mg, 2.5 mg, 25.0 mg/30 min). Plasma ACTH-levels were measured radioimmunologically at 10 minutes intervals. In four cases there was a remarkable decrease (P less than 0.005) in the ACTH plasma level of more than 50% as compared to the elevated starting levels of 800 to 1400 pg/ml. It is concluded that under certain circumstances MIF could play a role in the regulation of ACTH-secretion.", "contents": "Suppression of ACTH secretion by synthetic MSH-release inhibiting factor Pro-Leu-Gly-NH2 in Addison's disease. The regulation of release of MSH and ACTH seems to be closely related. The effect of Pro-Leu-Gly-NH2, the most active MSH-release inhibiting factor (MIF), was investigated on ACTH-hypersecretion in six patients suffering from primary adrenocortical insufficiency. MIF was infused at constant rates with stepwise increase in concentration (0.25 mg, 2.5 mg, 25.0 mg/30 min). Plasma ACTH-levels were measured radioimmunologically at 10 minutes intervals. In four cases there was a remarkable decrease (P less than 0.005) in the ACTH plasma level of more than 50% as compared to the elevated starting levels of 800 to 1400 pg/ml. It is concluded that under certain circumstances MIF could play a role in the regulation of ACTH-secretion."}
{"id": "PMID:16827", "title": "Isolation and partial characterization of plasma membranes from the livers of control and Streptococcus pneumoniae-infected rats.", "content": "Plasma membranes were isolated from the livers of control and Streptococcus  pneumoniae-infected rats. This work, therefore, represents the first isolation of plasma membranes from infected actron microscopy and by the use of enzyme markers for microsomes (glucose-6-phosphatase), mitochondria (glutamate and malate dehydrogenases), and lysosomes (acid phosphatase). Plasma membranes from infected cells banded at the same sucrose density as plasma membranes from uninfected cells. Moreover, equivalent amounts of plasma membranes could be isolated from control and infected rat livers. There were, however, significant alterations in the enzyme complement of the plasma membrane after infection. 5'-Nucleotidase activity was significantly decreased, whereas alkaline phosphatase activity was significantly increased. Kinetic analysis demonstrated that only the Vmax and not the Km of these two enzymes was changed, suggesting that the altered affinity of the enzymes for substrate was not the mechanism responsible for the observed alterations. No change in the mitochondrial enzyme markers was observed after infection, but the specific activity of microsomal glucose-6-phosphatase decreased significantly. Possible explanations for the observed alterations are discussed.", "contents": "Isolation and partial characterization of plasma membranes from the livers of control and Streptococcus pneumoniae-infected rats. Plasma membranes were isolated from the livers of control and Streptococcus  pneumoniae-infected rats. This work, therefore, represents the first isolation of plasma membranes from infected actron microscopy and by the use of enzyme markers for microsomes (glucose-6-phosphatase), mitochondria (glutamate and malate dehydrogenases), and lysosomes (acid phosphatase). Plasma membranes from infected cells banded at the same sucrose density as plasma membranes from uninfected cells. Moreover, equivalent amounts of plasma membranes could be isolated from control and infected rat livers. There were, however, significant alterations in the enzyme complement of the plasma membrane after infection. 5'-Nucleotidase activity was significantly decreased, whereas alkaline phosphatase activity was significantly increased. Kinetic analysis demonstrated that only the Vmax and not the Km of these two enzymes was changed, suggesting that the altered affinity of the enzymes for substrate was not the mechanism responsible for the observed alterations. No change in the mitochondrial enzyme markers was observed after infection, but the specific activity of microsomal glucose-6-phosphatase decreased significantly. Possible explanations for the observed alterations are discussed."}
{"id": "PMID:16828", "title": "Gamma-irradiated chymotrypsin-like proteins. II. Connection between inactivation and structural changes.", "content": "The radiation yeilds of unfolding (Gconf) determined by the method of tryptophan fluorescence coincide with the radiation yields of proteolytic inactivation (Gin) for chymotrypsin-like (CT-like) enzymes on irradiation in air, both in solution and in the dry state with futher dissolution at pH7. It can be supposed that the unfolding is the main process determining the proteolytic gamma-inactivation of CT-like enzymes. It was also shown that the transition of chymotrypsin and trypsin gamma-irradiated at acid pH to neutral pH is an additional action, leading to unfolding of part of the molecules.", "contents": "Gamma-irradiated chymotrypsin-like proteins. II. Connection between inactivation and structural changes. The radiation yeilds of unfolding (Gconf) determined by the method of tryptophan fluorescence coincide with the radiation yields of proteolytic inactivation (Gin) for chymotrypsin-like (CT-like) enzymes on irradiation in air, both in solution and in the dry state with futher dissolution at pH7. It can be supposed that the unfolding is the main process determining the proteolytic gamma-inactivation of CT-like enzymes. It was also shown that the transition of chymotrypsin and trypsin gamma-irradiated at acid pH to neutral pH is an additional action, leading to unfolding of part of the molecules."}
{"id": "PMID:16831", "title": "Effect of changes in Pco2 on intraocular tension.", "content": "Elevated levels of inspired CO2 and blood Pco2 resulted in moderate elevation of IOT. A marked rapid decrease in IOT to a level less than baseline value was noted when inspired CO2 was suddenly decreased to ambient levels. Decrease in IOT was more pronounced than the decrease in Pco2 and increase in blood pH. Changes in IOT appeared related to the rate of change of Pco2 rather than the actual level of Pco2. Increased ventilatory excursions with constant inspired CO2 levels did not cause any elevation of IOT, but a minimal compensatory drop in IOT below resting values occurred when increased ventilatory excursions were discontinued. It is postulated that the changes in IOT noted are the result of sudden changes in aqueous production or ocular blood volume.", "contents": "Effect of changes in Pco2 on intraocular tension. Elevated levels of inspired CO2 and blood Pco2 resulted in moderate elevation of IOT. A marked rapid decrease in IOT to a level less than baseline value was noted when inspired CO2 was suddenly decreased to ambient levels. Decrease in IOT was more pronounced than the decrease in Pco2 and increase in blood pH. Changes in IOT appeared related to the rate of change of Pco2 rather than the actual level of Pco2. Increased ventilatory excursions with constant inspired CO2 levels did not cause any elevation of IOT, but a minimal compensatory drop in IOT below resting values occurred when increased ventilatory excursions were discontinued. It is postulated that the changes in IOT noted are the result of sudden changes in aqueous production or ocular blood volume."}
{"id": "PMID:16834", "title": "Loss of histochemically demonstrable catecholamines in the glomus cells of the carotid body after alpha-methyl-para-tyrosine treatment.", "content": "A statistically significant decrease in the intensity of catecholamine fluorescence of some carotid body glomus cells was observed after inhibition of the enzyme tyrosine hydroxylase by injection of 80 mg/kg alpha-methyl-paratyrosine. The intensity of the formaldehyde-induced fluorescence was measured in individual glomus cells. The maximum decrease in the intensity was observed 4 to 6 hr after the alpha-methyltyrosine injection. This suggests a rapid turnover in the catecholamines of the carotid body.", "contents": "Loss of histochemically demonstrable catecholamines in the glomus cells of the carotid body after alpha-methyl-para-tyrosine treatment. A statistically significant decrease in the intensity of catecholamine fluorescence of some carotid body glomus cells was observed after inhibition of the enzyme tyrosine hydroxylase by injection of 80 mg/kg alpha-methyl-paratyrosine. The intensity of the formaldehyde-induced fluorescence was measured in individual glomus cells. The maximum decrease in the intensity was observed 4 to 6 hr after the alpha-methyltyrosine injection. This suggests a rapid turnover in the catecholamines of the carotid body."}
{"id": "PMID:16832", "title": "A new glucose 6-phosphate dehydrogenase variant (GDTrinacria) in two unrelated families of Sicilian ancestry.", "content": "A new G6PD variant in two unrelated families of Sicilian extraction is described. It is characterized by an enzyme activity amounting to 20% of normal, by a slow electrophoretic mobility, decreased Km values for both TPN and G6P, increased utilization of substrates analogues, thermolability and biphasic pH curve. It has been named G6PD Trinacria.", "contents": "A new glucose 6-phosphate dehydrogenase variant (GDTrinacria) in two unrelated families of Sicilian ancestry. A new G6PD variant in two unrelated families of Sicilian extraction is described. It is characterized by an enzyme activity amounting to 20% of normal, by a slow electrophoretic mobility, decreased Km values for both TPN and G6P, increased utilization of substrates analogues, thermolability and biphasic pH curve. It has been named G6PD Trinacria."}
{"id": "PMID:16833", "title": "Endopolygalacturonase, an extracellular pectic enzyme of Rhizoctonia fragariae.", "content": "A pectolytic enzyme from culture filtrates of Rhizoctonia fragariae was purified approx. 29-fold. The enzyme exhibited maximal depolymerizing activity on Na-polypectate rather than pectin at pH 5.0 and was inhibited at different extent by divalent cations Mg++, Mn++, Ca++. The analysis by paper chromatography of the products of enzyme hydrolysis suggested that the enzyme attacks the substrate by a random mechanism. The absorption spectrum of the chromogen formed by the hydrolysis products and thiobarbituric acid suggested that the enzyme is a hydrolytic enzyme. On the basis of these results the enzyme is classifiable as endo-polygalacturonase (poly alpha-1,4-galacturonide glycanohydrolase E.C. 3.2.1.15).", "contents": "Endopolygalacturonase, an extracellular pectic enzyme of Rhizoctonia fragariae. A pectolytic enzyme from culture filtrates of Rhizoctonia fragariae was purified approx. 29-fold. The enzyme exhibited maximal depolymerizing activity on Na-polypectate rather than pectin at pH 5.0 and was inhibited at different extent by divalent cations Mg++, Mn++, Ca++. The analysis by paper chromatography of the products of enzyme hydrolysis suggested that the enzyme attacks the substrate by a random mechanism. The absorption spectrum of the chromogen formed by the hydrolysis products and thiobarbituric acid suggested that the enzyme is a hydrolytic enzyme. On the basis of these results the enzyme is classifiable as endo-polygalacturonase (poly alpha-1,4-galacturonide glycanohydrolase E.C. 3.2.1.15)."}
{"id": "PMID:16859", "title": "Volume characteristics of extra- and intraparenchymal segments of the canine pulmonary artery.", "content": "The volumes of the extraparenchymal segment (VpaEP) and intraparenchymal segment (VpaIP) of the pulmonary arterial tree were determined in intact anesthetized dogs during room air breathing and acute hypoxia. Total pulmonary arterial blood volume (Vpatotal) was calculated as the product of pulmonary blood flow and pulmonary arterial circulation time. An angiographic technique was used to estimate VpEP. VpaIP was calculated by subtracting VpaEP from Vpatotal. During room air breathing at functional residual capacity, mean +/- SD of VpaEP was 17.1 +/- 5.1 ml and of VpaIP was 31.7 +/- 20.8 ml, representing 40% and 60%, respectively, of Vpatotal. Vpatotal increased 22.2 +/- 10.5 ml during lung inflation, with proportional increases in VpaIP and VpaEP. VpaEP was found to be influenced equally by changes in transmural pulmonary arterial and transpulmonary pressures. Acute hypoxia was accompanied by an increase in pulmonary vascular resistance and a decrease in volume distensibility of the extraparenchymal segment. Vpatotal increased 76% without changes in the relative volume distribution of VpaEP and VpaIP. These findings can be best explained by active vasomotion with an increase in down-stream pulmonary vascular resistance.", "contents": "Volume characteristics of extra- and intraparenchymal segments of the canine pulmonary artery. The volumes of the extraparenchymal segment (VpaEP) and intraparenchymal segment (VpaIP) of the pulmonary arterial tree were determined in intact anesthetized dogs during room air breathing and acute hypoxia. Total pulmonary arterial blood volume (Vpatotal) was calculated as the product of pulmonary blood flow and pulmonary arterial circulation time. An angiographic technique was used to estimate VpEP. VpaIP was calculated by subtracting VpaEP from Vpatotal. During room air breathing at functional residual capacity, mean +/- SD of VpaEP was 17.1 +/- 5.1 ml and of VpaIP was 31.7 +/- 20.8 ml, representing 40% and 60%, respectively, of Vpatotal. Vpatotal increased 22.2 +/- 10.5 ml during lung inflation, with proportional increases in VpaIP and VpaEP. VpaEP was found to be influenced equally by changes in transmural pulmonary arterial and transpulmonary pressures. Acute hypoxia was accompanied by an increase in pulmonary vascular resistance and a decrease in volume distensibility of the extraparenchymal segment. Vpatotal increased 76% without changes in the relative volume distribution of VpaEP and VpaIP. These findings can be best explained by active vasomotion with an increase in down-stream pulmonary vascular resistance."}
{"id": "PMID:16860", "title": "Comparison of arm versus leg work in induction of acute episodes of asthma.", "content": "The severity of exercise-induced asthma varies with the type of exercise performed. To determine whether such variation could be attributed to the use of different muscle groups, we exercised arms separately from legs using a bicycle ergometer. First, arms were exercised to exhaustion, then legs were exercised at the same load for the same duration. Arm work resulted in greater ventilation, heart rate, hydrogen ion concentration, and airway obstruction than did leg work. Later, legs were exercised to exhaustion using a load more than twice that of the arm work. Both the exhausting leg work and exhausting arm work resulted in significant bronchospasm and acidosis, whereas the nonexhausting leg work did not. These data suggest that, in arm and/or leg exercise, the relationship of work load to muscle mass is a determinant of airway obstruction.", "contents": "Comparison of arm versus leg work in induction of acute episodes of asthma. The severity of exercise-induced asthma varies with the type of exercise performed. To determine whether such variation could be attributed to the use of different muscle groups, we exercised arms separately from legs using a bicycle ergometer. First, arms were exercised to exhaustion, then legs were exercised at the same load for the same duration. Arm work resulted in greater ventilation, heart rate, hydrogen ion concentration, and airway obstruction than did leg work. Later, legs were exercised to exhaustion using a load more than twice that of the arm work. Both the exhausting leg work and exhausting arm work resulted in significant bronchospasm and acidosis, whereas the nonexhausting leg work did not. These data suggest that, in arm and/or leg exercise, the relationship of work load to muscle mass is a determinant of airway obstruction."}
{"id": "PMID:16861", "title": "Ventilatory response in the fetal lamb following peripheral chemodenervation.", "content": "Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors.", "contents": "Ventilatory response in the fetal lamb following peripheral chemodenervation. Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors."}
{"id": "PMID:16862", "title": "H+ transport from CNS in hypercapnia and regulation of CSF [HCO3-].", "content": "CSF HCO3- increases more than plasma HCO3- in hypercapnia, and there are at least two sources for the CSF HCO3- increase--one derived from the simultaneous increase in plasma HCO3-, and the other, HCO3-formed from hydration of CO2 in the choroid plexus and glia and susceptible to inhibition by acetazolamide (J. Appl. Physiol. 38: 504-512, 1975). It was proposed that the H+ formed in the CNS in CO2 hydration is actively exchanged for plasma Na+ utilizing the Na-K ATPase pump. H+ transport from the CNS was therefore studied in four groups of dogs breathing 5% CO2 at constant VA for 4 h with repeated injections of saline, acetazolamide 5 mg/ml, ouabain 0.1 mg/ml, and acetazolamide and ouabain together into lateral cerebral ventricles. Arterial HCO3-increased 2.5 meq/l at 4 h of hypercapnia in all groups. CSF HCO3-increased 5.8 meq/l in the saline-injected animals, but it increased only about 2 meq/l and equaled plasma HCO3- rise in the other three groups. Therefore CNS HCO3- formation in hypercapnia can be blocked by inhibiting the CO2 hydration reaction with acetazolamide or by blocking H+ removal by inhibiting Na-K ATPase with ouabain. The data support the thesis of active H+ removal from the CNS in exchange for plasma Na+ in hypercapnia.", "contents": "H+ transport from CNS in hypercapnia and regulation of CSF [HCO3-]. CSF HCO3- increases more than plasma HCO3- in hypercapnia, and there are at least two sources for the CSF HCO3- increase--one derived from the simultaneous increase in plasma HCO3-, and the other, HCO3-formed from hydration of CO2 in the choroid plexus and glia and susceptible to inhibition by acetazolamide (J. Appl. Physiol. 38: 504-512, 1975). It was proposed that the H+ formed in the CNS in CO2 hydration is actively exchanged for plasma Na+ utilizing the Na-K ATPase pump. H+ transport from the CNS was therefore studied in four groups of dogs breathing 5% CO2 at constant VA for 4 h with repeated injections of saline, acetazolamide 5 mg/ml, ouabain 0.1 mg/ml, and acetazolamide and ouabain together into lateral cerebral ventricles. Arterial HCO3-increased 2.5 meq/l at 4 h of hypercapnia in all groups. CSF HCO3-increased 5.8 meq/l in the saline-injected animals, but it increased only about 2 meq/l and equaled plasma HCO3- rise in the other three groups. Therefore CNS HCO3- formation in hypercapnia can be blocked by inhibiting the CO2 hydration reaction with acetazolamide or by blocking H+ removal by inhibiting Na-K ATPase with ouabain. The data support the thesis of active H+ removal from the CNS in exchange for plasma Na+ in hypercapnia."}
{"id": "PMID:16863", "title": "Hematology, viscosity, and respiratory functions of whole blood of the lesser mouse deer, Tragulus javanicus.", "content": "Blood samples from the lesser mouse deer were examined for hematology, viscosity, oxygen dissociation curve, and magnitude of the Bohr effect. Red corpuscle dimensions, determined under oil immersion with an ocular micrometer, averaged 2.2 micron while the cell counts averaged 53 million/micronl blood, and the packed cell volume averaged 31.2%. Blood hemoglobin concentration averaged 11.2 g/100 ml and the calculated mean cell hemoglobin concentration was 38 g/100 ml. The relative viscosity of the mouse deer plasma was 1.97 and increased in a nonlinear manner with hematocrit to 100 at 80% packed cell volume. Oxygen-hemoglobin equilibrium curves, determined with a mixing technique at 37 degrees C and 10, 36 and 71 Torr PCO2, have the same configuration observed in blood from mammals in general. The P50 of the mouse deer blood at pH = 7.40 is 34 Torr and the Bohr effect (deltalog P50/deltapH) is -0.483. The mouse deer have blood hematocrits which are well below the hematocrits observed in mammals with larger erythrocytes, but similar to the blood hematocrits observed in other mammals with small erythrocytes. We suggest that the low hematocrit is an adaptation which circumvents the hemodynamic problems associated with a high blood viscosity and that, in the mouse deer, the expected concomitantly low total blood hemoglobin concentration is compensated by a higher than average mean cell hemoglobin concentration.", "contents": "Hematology, viscosity, and respiratory functions of whole blood of the lesser mouse deer, Tragulus javanicus. Blood samples from the lesser mouse deer were examined for hematology, viscosity, oxygen dissociation curve, and magnitude of the Bohr effect. Red corpuscle dimensions, determined under oil immersion with an ocular micrometer, averaged 2.2 micron while the cell counts averaged 53 million/micronl blood, and the packed cell volume averaged 31.2%. Blood hemoglobin concentration averaged 11.2 g/100 ml and the calculated mean cell hemoglobin concentration was 38 g/100 ml. The relative viscosity of the mouse deer plasma was 1.97 and increased in a nonlinear manner with hematocrit to 100 at 80% packed cell volume. Oxygen-hemoglobin equilibrium curves, determined with a mixing technique at 37 degrees C and 10, 36 and 71 Torr PCO2, have the same configuration observed in blood from mammals in general. The P50 of the mouse deer blood at pH = 7.40 is 34 Torr and the Bohr effect (deltalog P50/deltapH) is -0.483. The mouse deer have blood hematocrits which are well below the hematocrits observed in mammals with larger erythrocytes, but similar to the blood hematocrits observed in other mammals with small erythrocytes. We suggest that the low hematocrit is an adaptation which circumvents the hemodynamic problems associated with a high blood viscosity and that, in the mouse deer, the expected concomitantly low total blood hemoglobin concentration is compensated by a higher than average mean cell hemoglobin concentration."}
{"id": "PMID:16864", "title": "Effects of potassium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells.", "content": "Bacteria transduce and conserve energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). Energized cells of Streptococcus lactis accumulate K+ ions presumably in exchange for H+. We reasoned that if the movement of H+ is limited, then an increase in H+ efflux, effected by potassium transport inward, should result in changes in the steady-state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltapH) from the distribution of a weak acid. The deltap was also determined independently from the accumulation levels of the non-metabolizable sugar thiomethyl-beta-galactoside. KCl addition to cells fermenting glucose or arginine at pH 5 changed the deltap very little, but lowered the deltapsi, while increasing the deltapH. At pH 7, the deltapH only increased slightly; thus, the decrease in deltapsi, effected by addition of potassium ions, resulted in a lowered steady-state deltap. These effects were shown not to be due to swelling or shrinking of the cells. Thus, in these nongrowing cells, under conditions of energy utilization for the active transport of K+, the components of deltap can vary depending on the limitations on the net movement of protons.", "contents": "Effects of potassium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells. Bacteria transduce and conserve energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). Energized cells of Streptococcus lactis accumulate K+ ions presumably in exchange for H+. We reasoned that if the movement of H+ is limited, then an increase in H+ efflux, effected by potassium transport inward, should result in changes in the steady-state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltapH) from the distribution of a weak acid. The deltap was also determined independently from the accumulation levels of the non-metabolizable sugar thiomethyl-beta-galactoside. KCl addition to cells fermenting glucose or arginine at pH 5 changed the deltap very little, but lowered the deltapsi, while increasing the deltapH. At pH 7, the deltapH only increased slightly; thus, the decrease in deltapsi, effected by addition of potassium ions, resulted in a lowered steady-state deltap. These effects were shown not to be due to swelling or shrinking of the cells. Thus, in these nongrowing cells, under conditions of energy utilization for the active transport of K+, the components of deltap can vary depending on the limitations on the net movement of protons."}
{"id": "PMID:16865", "title": "Purification and properties of cis-toluene dihydrodiol dehydrogenase from Pseudomonas putida.", "content": "The purification of (+)-cis-1(S),2(R)-dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase from cells of Pseudomonas putida grown with toluene as the sole source of carbon and energy is reported. The molecular weight of the enzyme is 104,000 at pH 9.7. The enzyme is composed of four apparently identical subunits with molecular weights of 27,000. The enzyme is specific for nicotinamide adenine dinucleotide and oxidizes a number of cis-dihydrodiols. Both enantiomers of a racemic mixture of cis-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol are oxidized by the enzyme. No enzymatic activity is observed with trans-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol.", "contents": "Purification and properties of cis-toluene dihydrodiol dehydrogenase from Pseudomonas putida. The purification of (+)-cis-1(S),2(R)-dihydroxy-3-methylcyclohexa-3,5-diene dehydrogenase from cells of Pseudomonas putida grown with toluene as the sole source of carbon and energy is reported. The molecular weight of the enzyme is 104,000 at pH 9.7. The enzyme is composed of four apparently identical subunits with molecular weights of 27,000. The enzyme is specific for nicotinamide adenine dinucleotide and oxidizes a number of cis-dihydrodiols. Both enantiomers of a racemic mixture of cis-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol are oxidized by the enzyme. No enzymatic activity is observed with trans-1,2-dihydroxyl-1,2-dihydronaphthalene dihydrodiol."}
{"id": "PMID:16866", "title": "Purification and characterization of a neutral protease from Saccharomycopsis lipolytica.", "content": "Saccharomycopsis lipolytica 37-1 produced two inducible extracellular proteases, one under neutral or alkaline growth conditions and the second under acid conditions. Secretion of the neutral protease was repressed in the presence of glycerol or glucose, both of which supported rapid growth of the organism. Ammonium ions also repressed the secretion of the enzyme. The neutral protease activity copurified with esterase activity during ammonium sulfate fractionation, chromatography on diethylaminoethyl-cellulose, and gel filtration on Sephadex G-150. The molecular weight of the enzyme was estimated to be 42,000 by sucrose density gradient centrifugation and 38,500 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme had a pH optimum of 6.8. Phenylmethylsulfonylfluoride inhibited both protease and esterase activities, indicating the presence of a serine residue in the active center. Protease, but not esterase, activity was sensitive to ethylenediaminetetraacetate and was significantly activated by divalent ions. Dithiothreitol inhibited both protease and esterase activities, indicating the presence of a critical disulfide bridge. The enzyme hydrolyzed casein (K(m) = 25.6 muM) and hemoglobin as well as the nitrophenyl esters of tyrosine (K(m) = 2.4 mM), glycine, tryptophan, and phenylalanine.", "contents": "Purification and characterization of a neutral protease from Saccharomycopsis lipolytica. Saccharomycopsis lipolytica 37-1 produced two inducible extracellular proteases, one under neutral or alkaline growth conditions and the second under acid conditions. Secretion of the neutral protease was repressed in the presence of glycerol or glucose, both of which supported rapid growth of the organism. Ammonium ions also repressed the secretion of the enzyme. The neutral protease activity copurified with esterase activity during ammonium sulfate fractionation, chromatography on diethylaminoethyl-cellulose, and gel filtration on Sephadex G-150. The molecular weight of the enzyme was estimated to be 42,000 by sucrose density gradient centrifugation and 38,500 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme had a pH optimum of 6.8. Phenylmethylsulfonylfluoride inhibited both protease and esterase activities, indicating the presence of a serine residue in the active center. Protease, but not esterase, activity was sensitive to ethylenediaminetetraacetate and was significantly activated by divalent ions. Dithiothreitol inhibited both protease and esterase activities, indicating the presence of a critical disulfide bridge. The enzyme hydrolyzed casein (K(m) = 25.6 muM) and hemoglobin as well as the nitrophenyl esters of tyrosine (K(m) = 2.4 mM), glycine, tryptophan, and phenylalanine."}
{"id": "PMID:16867", "title": "6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) from slow-growing Rhizobia.", "content": "6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) (NAD+-6PGD) was detected in several slow-growing strains of rhizobia, and no activity involving NADP+ was found in the same extracts. By contrast, fast-growing strains of rhizobia had NADP+-6PGD activity; most of them also had NAD+-6PGD activity. NAD+-6PGD was partially purified from the slow-growing strain Rhizobium japonicum 5006. The reaction was shown to be an oxidative decarboxylation.", "contents": "6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) from slow-growing Rhizobia. 6-Phospho-D-gluconate:NAD+ 2-oxidoreductase (decarboxylating) (NAD+-6PGD) was detected in several slow-growing strains of rhizobia, and no activity involving NADP+ was found in the same extracts. By contrast, fast-growing strains of rhizobia had NADP+-6PGD activity; most of them also had NAD+-6PGD activity. NAD+-6PGD was partially purified from the slow-growing strain Rhizobium japonicum 5006. The reaction was shown to be an oxidative decarboxylation."}
{"id": "PMID:16868", "title": "Regulation of enzyme synthesis by the glutamine synthetase of Salmonella typhimurium: a factor in addition to glutamine synthetase is required for activation of enzyme formation.", "content": "In Klebsiella aerogenes but not in Salmonella typhimurium glutamine synthetase can function during nitrogen-limited growth to increase the rate of synthesis of histidase from the hut genes of S. typhimurium 15-59 (hutS. 15-59). Formation of proline oxidase is also not increased in nitrogen-limited cultures of S. typhimurium. However, in hybrid strains of Escherichia coli or K. aerogenes, the glutamine synthetase of S. typhimurium activates synthesis of histidase from the hutS. 15-59 genes. Apparently, glutamine synthetase is necessary but not sufficient for activation of transcription of the hut genes; another factor must also be present. This factor is active in both K. aerogenes and E. coli but is missing or altered in S. typhimurium.", "contents": "Regulation of enzyme synthesis by the glutamine synthetase of Salmonella typhimurium: a factor in addition to glutamine synthetase is required for activation of enzyme formation. In Klebsiella aerogenes but not in Salmonella typhimurium glutamine synthetase can function during nitrogen-limited growth to increase the rate of synthesis of histidase from the hut genes of S. typhimurium 15-59 (hutS. 15-59). Formation of proline oxidase is also not increased in nitrogen-limited cultures of S. typhimurium. However, in hybrid strains of Escherichia coli or K. aerogenes, the glutamine synthetase of S. typhimurium activates synthesis of histidase from the hutS. 15-59 genes. Apparently, glutamine synthetase is necessary but not sufficient for activation of transcription of the hut genes; another factor must also be present. This factor is active in both K. aerogenes and E. coli but is missing or altered in S. typhimurium."}
{"id": "PMID:16870", "title": "Alkaline serine proteinases D and E of Streptomyces griseus K-1.", "content": "Two DFP-sensitive alkaline proteinases with strong esterase activity toward Ac-(Ala)3-OMe, designated as alkaline serine proteinases D and E, were purified pronase, a protease mixture from St. griseus K-1. Each was shown to be homogeneous by acrylamide disc gel electrophoresis. The molecular weights of these enzymes were estimated to be about 27,000 be gel filtration. Studies on their actions on acyl-tl-amino acid methyl or ethyl esters indicated that proteinases D and E both exhibited a broad substrate specificity and hydrolyzed the ester bonds of esters containing Trp, Tyr, Phe, Leu, and Ala. The esterase activities of both enzymes toward Ac-(Ala)3-OMe were the highest among proteinases so far isolated from various sources. Proteinases D and E also lacked cystine residues in their molecules, being entirely different from alkaline serine proteinases A, B, and C in pronase. Some differences were , however, observed between them as regards pH stability, behavior on CM-cellulose, mobility on polyacrylamide electrophoresis, and amidase activity toward Suc-(Ala)3-pNA.", "contents": "Alkaline serine proteinases D and E of Streptomyces griseus K-1. Two DFP-sensitive alkaline proteinases with strong esterase activity toward Ac-(Ala)3-OMe, designated as alkaline serine proteinases D and E, were purified pronase, a protease mixture from St. griseus K-1. Each was shown to be homogeneous by acrylamide disc gel electrophoresis. The molecular weights of these enzymes were estimated to be about 27,000 be gel filtration. Studies on their actions on acyl-tl-amino acid methyl or ethyl esters indicated that proteinases D and E both exhibited a broad substrate specificity and hydrolyzed the ester bonds of esters containing Trp, Tyr, Phe, Leu, and Ala. The esterase activities of both enzymes toward Ac-(Ala)3-OMe were the highest among proteinases so far isolated from various sources. Proteinases D and E also lacked cystine residues in their molecules, being entirely different from alkaline serine proteinases A, B, and C in pronase. Some differences were , however, observed between them as regards pH stability, behavior on CM-cellulose, mobility on polyacrylamide electrophoresis, and amidase activity toward Suc-(Ala)3-pNA."}
{"id": "PMID:16871", "title": "Amino acid sequence of a cyanogen bromide fragment containing the two tryptophanyl residues of lobster arginine kinase (Homarus vulgaris).", "content": "Lobster arginine kinase [EC 2.7.3.3] contains 2 tryptophanyl residues and 9 methionyl residues. The whole carboxymethylated protein was first subjected to CNBr cleavage and the resulting fragments were isolated by gel filtration and other experimental approaches. One fragment, CB5, which contains 60 residues including the two tryptophanyl residues and two of the five cysteinyl residues of the protein, was characterized and the results are reported inthis paper. The overall strategy for the establishment of the complete sequence of this fragment was based on the use of three types of peptides: (a) whole cyanogen bromide peptide CB5 which was partially characterized by automatic Edman degradation using a sequencer: 42 steps were performed out of 60 residues, (b) tryptic peptides of CB5, (c) peptides formed by cleavage of S-carboxymethylated arginine kinase (whole protein) at the two tryptophanyl residues with BNPS-skatole. The complete amino acid sequence of the CNBr polypeptide (CB5) which contains the two tryptophanyl residues of the whole protein was established.", "contents": "Amino acid sequence of a cyanogen bromide fragment containing the two tryptophanyl residues of lobster arginine kinase (Homarus vulgaris). Lobster arginine kinase [EC 2.7.3.3] contains 2 tryptophanyl residues and 9 methionyl residues. The whole carboxymethylated protein was first subjected to CNBr cleavage and the resulting fragments were isolated by gel filtration and other experimental approaches. One fragment, CB5, which contains 60 residues including the two tryptophanyl residues and two of the five cysteinyl residues of the protein, was characterized and the results are reported inthis paper. The overall strategy for the establishment of the complete sequence of this fragment was based on the use of three types of peptides: (a) whole cyanogen bromide peptide CB5 which was partially characterized by automatic Edman degradation using a sequencer: 42 steps were performed out of 60 residues, (b) tryptic peptides of CB5, (c) peptides formed by cleavage of S-carboxymethylated arginine kinase (whole protein) at the two tryptophanyl residues with BNPS-skatole. The complete amino acid sequence of the CNBr polypeptide (CB5) which contains the two tryptophanyl residues of the whole protein was established."}
{"id": "PMID:16872", "title": "Purification and characterization of arylamidase from monkey brain.", "content": "Arylamidase [EC3.4.11.2] was isolated from monkey brain extract and purified about 2100-fold in approximately 11% yield by a six-step procedure comprising extraction from monkey brain homogenate, ammonium sulfate fractionation, first hydroxylapatite chromatography, DEAE-cellulose chromatography, Sephadex G-200 gell filtration and second hydroxylapatite chromatography. The enzyme showed a single band on polyacrylamide disc electrophoresis and consisted of a single polypeptide chain, as judged by disc electrophoresis in the presence of sodium dodecyl sulfate. The enzyme was strongly inhibited by PCMB, TPCK, and puromycin. Puromycin competitively inhibited the enzyme and the Ii value was about 5 x 10(-7)M. Treatment with EDTA resulted in a loss of enzyme activity. The enzyme activity was restored by addition of Zn2+, Co2+, Mn2+. Among various amino acid beta-naphthylamides, L-alanine beta-naphthylamide was most rapidly hydrolyzed and N-carbobenzoxyl-L-leucine beta-naphthylamide was not hydrolyzed by this enzyme preparation. The molecular weight of the enzyme was 92,000 as determined by gel filtration on Sephadex G-200.", "contents": "Purification and characterization of arylamidase from monkey brain. Arylamidase [EC3.4.11.2] was isolated from monkey brain extract and purified about 2100-fold in approximately 11% yield by a six-step procedure comprising extraction from monkey brain homogenate, ammonium sulfate fractionation, first hydroxylapatite chromatography, DEAE-cellulose chromatography, Sephadex G-200 gell filtration and second hydroxylapatite chromatography. The enzyme showed a single band on polyacrylamide disc electrophoresis and consisted of a single polypeptide chain, as judged by disc electrophoresis in the presence of sodium dodecyl sulfate. The enzyme was strongly inhibited by PCMB, TPCK, and puromycin. Puromycin competitively inhibited the enzyme and the Ii value was about 5 x 10(-7)M. Treatment with EDTA resulted in a loss of enzyme activity. The enzyme activity was restored by addition of Zn2+, Co2+, Mn2+. Among various amino acid beta-naphthylamides, L-alanine beta-naphthylamide was most rapidly hydrolyzed and N-carbobenzoxyl-L-leucine beta-naphthylamide was not hydrolyzed by this enzyme preparation. The molecular weight of the enzyme was 92,000 as determined by gel filtration on Sephadex G-200."}
{"id": "PMID:16873", "title": "Anhydrotrypsin: new features in ligand interactions revealed by affinity chromatography and thionine replacement.", "content": "Anhydrotrypsin was isolated in high purity from the product of base elimination from phenylmethanesulfonyl-trypsin, by a single operation of affinity chromatography. The adsorbent used for the chromatography was an agarose derivative coupled with peptides containing C-terminal arginine residues. As the affinity of the adsorbent for anhydrotrypsin was high compared with that for trypsin, purification of the enzyme derivative was easily achieved without the prior inactivation of trypsin which had been regenerated during the elimination reaction. Comparative studies of the ligand interaction specificities with anhydrotrypsin and trypsin confirmed the stronger interaction of the former protein with product-type ligands such as Bz-Arg-OH. No marked differences were observed between them in affinities toward substrate-type ligands such as Bz-Arg-NH2. The higher affinity of anhydrotrypsin was found to be limited to product-type ligands of L-configuration, i.e., the protein displayed an ability to discriminate the L-ligand from its optical isomer. THE PKa value for the ionization form of anhydrotrypsin responsible for the interaction with Bz-Arg-OH was estimated to be 7.60+/-0907", "contents": "Anhydrotrypsin: new features in ligand interactions revealed by affinity chromatography and thionine replacement. Anhydrotrypsin was isolated in high purity from the product of base elimination from phenylmethanesulfonyl-trypsin, by a single operation of affinity chromatography. The adsorbent used for the chromatography was an agarose derivative coupled with peptides containing C-terminal arginine residues. As the affinity of the adsorbent for anhydrotrypsin was high compared with that for trypsin, purification of the enzyme derivative was easily achieved without the prior inactivation of trypsin which had been regenerated during the elimination reaction. Comparative studies of the ligand interaction specificities with anhydrotrypsin and trypsin confirmed the stronger interaction of the former protein with product-type ligands such as Bz-Arg-OH. No marked differences were observed between them in affinities toward substrate-type ligands such as Bz-Arg-NH2. The higher affinity of anhydrotrypsin was found to be limited to product-type ligands of L-configuration, i.e., the protein displayed an ability to discriminate the L-ligand from its optical isomer. THE PKa value for the ionization form of anhydrotrypsin responsible for the interaction with Bz-Arg-OH was estimated to be 7.60+/-0907"}
{"id": "PMID:16874", "title": "Glutathione reductase in the sea urchin egg. III. Activation of the complex form by proteinases.", "content": "The G-200 flow-through fraction of the extract of sea urchin eggs contained a complex form of glutathione reductase (GR) [EC 1.6.4.2]. The complex was unstable and gradually dissociated with ain increase in GR activity. The activation was facilitated by high concentrations of EDTA, KCI or (NH4)2SO4. The rate of activation by salts was apparently dependent on the ionic strength. The complex form was also activated rather quickly by treatment with proteinases such as trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1] or subtilisin [EC 3.4.21.14]. Trypsin caused the complex to release the free form of GR. Even after trypsin treatment, little change was observed in the dependence of the GR activity on GSSG or NADPH concentration. The GR activity of the complex form was not inhibited at all by 0.2 mM N-ethylmaleimide (NEM) in the presence of GSSG, but was reduced to 3% in the presence of NADPH. When excess NEM was sequestered with GSH, the NEM-treated complex form was strikingly activated by trypsin, while no activation was detected with the free form of enzyme pretreated with NEM. These results suggest that the active site of GR in the complex form is largely masked by a polypeptide moiety of theinhbitiory component.", "contents": "Glutathione reductase in the sea urchin egg. III. Activation of the complex form by proteinases. The G-200 flow-through fraction of the extract of sea urchin eggs contained a complex form of glutathione reductase (GR) [EC 1.6.4.2]. The complex was unstable and gradually dissociated with ain increase in GR activity. The activation was facilitated by high concentrations of EDTA, KCI or (NH4)2SO4. The rate of activation by salts was apparently dependent on the ionic strength. The complex form was also activated rather quickly by treatment with proteinases such as trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1] or subtilisin [EC 3.4.21.14]. Trypsin caused the complex to release the free form of GR. Even after trypsin treatment, little change was observed in the dependence of the GR activity on GSSG or NADPH concentration. The GR activity of the complex form was not inhibited at all by 0.2 mM N-ethylmaleimide (NEM) in the presence of GSSG, but was reduced to 3% in the presence of NADPH. When excess NEM was sequestered with GSH, the NEM-treated complex form was strikingly activated by trypsin, while no activation was detected with the free form of enzyme pretreated with NEM. These results suggest that the active site of GR in the complex form is largely masked by a polypeptide moiety of theinhbitiory component."}
{"id": "PMID:16875", "title": "A new enzyme, NADPH-dihydropteridine reductase in bovine liver.", "content": "An enzyme designated as NADPH-dihydropteridine reductase was found in the extract of bovine liver and partially purified. In contrast to NADH-dpendent dihydropteridine reductase [EC 1.6.99.7], the enzyme catalyzes the reduction of quinonid-dihydropterin to tetrahydropterin in the presence of NADPH. The two enzymes were separated by column chromatography on DEAE-sephadex. Tyrosine formation in the phenylalanine hydroxylation system was also stimulated by NADPH-dihydropteridine reductase. The existence of these two dihydropteridine reductases suggests that the tetrahydro from ofpteridine cofactor may be regenerated in two different ways in vivo.", "contents": "A new enzyme, NADPH-dihydropteridine reductase in bovine liver. An enzyme designated as NADPH-dihydropteridine reductase was found in the extract of bovine liver and partially purified. In contrast to NADH-dpendent dihydropteridine reductase [EC 1.6.99.7], the enzyme catalyzes the reduction of quinonid-dihydropterin to tetrahydropterin in the presence of NADPH. The two enzymes were separated by column chromatography on DEAE-sephadex. Tyrosine formation in the phenylalanine hydroxylation system was also stimulated by NADPH-dihydropteridine reductase. The existence of these two dihydropteridine reductases suggests that the tetrahydro from ofpteridine cofactor may be regenerated in two different ways in vivo."}
{"id": "PMID:16876", "title": "Glycolysis of red cells suspended in solutions of impermeable solutes. Intracellular pH and glycolysis.", "content": "The glycolytic rate human red cells suspended in a sucrose medium of low or physiological pH was higher than that of the cells suspended in Ringer's medium of the same. pH. The medium pHP-glycolytic rate curve of red cells suspended in soucrose media shifted to the acidic side by about one unit compared with that of cells suspended in Ringer's medium. Similarly, the pattern of glycolytic intermediates in red cells suspended in a sucrose medium resembled that in cells suspended in Ringer's solution of about one unit higher pH. These phenomena could be ascribed to the change of intracellular pH, which was measured by the 5,5'-dimethyl-oxazolidine-2,4-dione method. A similar stimulation of glycolysis was observed when sodium citrate was added to red cells suspended in Ringer's solution at constant pH. These observations indicate that membrane-impermeable non-electrolytes or anions stimulate glycolysis of red cells by elevation ofthe intracellular pH. Red cell glycolysis is influenced mainly by the intracellular pH rather than by the pH of the suspending medium.", "contents": "Glycolysis of red cells suspended in solutions of impermeable solutes. Intracellular pH and glycolysis. The glycolytic rate human red cells suspended in a sucrose medium of low or physiological pH was higher than that of the cells suspended in Ringer's medium of the same. pH. The medium pHP-glycolytic rate curve of red cells suspended in soucrose media shifted to the acidic side by about one unit compared with that of cells suspended in Ringer's medium. Similarly, the pattern of glycolytic intermediates in red cells suspended in a sucrose medium resembled that in cells suspended in Ringer's solution of about one unit higher pH. These phenomena could be ascribed to the change of intracellular pH, which was measured by the 5,5'-dimethyl-oxazolidine-2,4-dione method. A similar stimulation of glycolysis was observed when sodium citrate was added to red cells suspended in Ringer's solution at constant pH. These observations indicate that membrane-impermeable non-electrolytes or anions stimulate glycolysis of red cells by elevation ofthe intracellular pH. Red cell glycolysis is influenced mainly by the intracellular pH rather than by the pH of the suspending medium."}
{"id": "PMID:16877", "title": "Actin-induced local conformational change in the myosin molecule. I. Effect of metal ions and nucleotides on the conformational change around a specific thiol group (S2) of heavy meromyosin.", "content": "As previously reported when a specific thiol group, S2, of myosin reacts with N-ethylmaleimide (NEM), its Ca2+-ATPase activity is decreased. Therefore, the reactivity of S2 can be estimated by measuring the decrement of the enzymatic activity. Using the change in the reactivity as a structural probe, we investigated whether F-actin affects the conformation around the region containing S2 under physiological conditions (at neutral pH and low ionic strength). 1. Experiments were carried out with heavy meromyosin (HMM), S1 of which had heen blocked with NEM, to observe the reactivity of S2 alone. In the experiments done in the presence of F-actin, the Ca2+-ATPase activity was measured using the heavy meromyosin fraction after actin had been removed by centrifugation and gel filtration. 2. ATP and other nucleotides activated the reactivity of S2 in the presence of Mg2+. On the other hand, F-actin markedly activated the reactivity of S2 which had been increased by ATP, but not by the other nucleotides. 3. The above cooperative action of F-actin with ATP was not observed in the presence of Ca2+ instead of Mg2+, or above 0.2 M KCl. These results suggest that the S2 region of the myosin molecule is a key region in the molecular interaction of the actin myosin-ATP system under physiological conditions.", "contents": "Actin-induced local conformational change in the myosin molecule. I. Effect of metal ions and nucleotides on the conformational change around a specific thiol group (S2) of heavy meromyosin. As previously reported when a specific thiol group, S2, of myosin reacts with N-ethylmaleimide (NEM), its Ca2+-ATPase activity is decreased. Therefore, the reactivity of S2 can be estimated by measuring the decrement of the enzymatic activity. Using the change in the reactivity as a structural probe, we investigated whether F-actin affects the conformation around the region containing S2 under physiological conditions (at neutral pH and low ionic strength). 1. Experiments were carried out with heavy meromyosin (HMM), S1 of which had heen blocked with NEM, to observe the reactivity of S2 alone. In the experiments done in the presence of F-actin, the Ca2+-ATPase activity was measured using the heavy meromyosin fraction after actin had been removed by centrifugation and gel filtration. 2. ATP and other nucleotides activated the reactivity of S2 in the presence of Mg2+. On the other hand, F-actin markedly activated the reactivity of S2 which had been increased by ATP, but not by the other nucleotides. 3. The above cooperative action of F-actin with ATP was not observed in the presence of Ca2+ instead of Mg2+, or above 0.2 M KCl. These results suggest that the S2 region of the myosin molecule is a key region in the molecular interaction of the actin myosin-ATP system under physiological conditions."}
{"id": "PMID:16878", "title": "Ciliary dynein from sea urchin embryos.", "content": "Axonemal dynein ATPase [EC 3.6.1.3] was extracted from cilia of sea urchin embryos for a study of its enzymatic properties. Sedimentation analysis on a sucrose density gradient revealed that ATPase activity was associated with the 12S particles. The partially purified 12S enzyme was characterized mainly with regard to the optimum pH, divalent cation and ionic strength requirments and substrate specificity. Comparative investigation of the data obtained indicates that the properties of the present dyneine ATPase resemble those of other dynein(-like) ATPase hitherto reported. In addition, the possible relationship among dyneins within a single species, in particular between the ciliary dynein and cytoplasmic dynein-like ATPase, is discussed.", "contents": "Ciliary dynein from sea urchin embryos. Axonemal dynein ATPase [EC 3.6.1.3] was extracted from cilia of sea urchin embryos for a study of its enzymatic properties. Sedimentation analysis on a sucrose density gradient revealed that ATPase activity was associated with the 12S particles. The partially purified 12S enzyme was characterized mainly with regard to the optimum pH, divalent cation and ionic strength requirments and substrate specificity. Comparative investigation of the data obtained indicates that the properties of the present dyneine ATPase resemble those of other dynein(-like) ATPase hitherto reported. In addition, the possible relationship among dyneins within a single species, in particular between the ciliary dynein and cytoplasmic dynein-like ATPase, is discussed."}
{"id": "PMID:16879", "title": "Amino acid sequences around 1, 2-epoxy-3-(p-nitrophenoxy)propane-reactive residues in rhizopus chinensis acid protease: homology with pepsin and rennin.", "content": "Two different peptides containing an aspartyl residue reactive with 1, 2-epoxy-3-(p-nitrophenoxy)propane (EPNP) in the acid protease from Rhizopus chinensis were isolated from a peptic digest of the EPNP-modified enzyme. One of the peptides was sequenced as Asp-Thr-Gly-Ser-Asp. The amino acid sequence had very high homology with those around the EPNP-reactive aspartyl residues in rennin (chymosin) [EC 3.4.23.4] and pepsin [EC 3.4.23.1]. The other peptide contained no methionine residue and gave the sequence: Asp-Thr-Gly-Thr-Thr-Leu. The N-terminal aspartyl residue of each peptide was deduced to be the EPNP-reactive site.", "contents": "Amino acid sequences around 1, 2-epoxy-3-(p-nitrophenoxy)propane-reactive residues in rhizopus chinensis acid protease: homology with pepsin and rennin. Two different peptides containing an aspartyl residue reactive with 1, 2-epoxy-3-(p-nitrophenoxy)propane (EPNP) in the acid protease from Rhizopus chinensis were isolated from a peptic digest of the EPNP-modified enzyme. One of the peptides was sequenced as Asp-Thr-Gly-Ser-Asp. The amino acid sequence had very high homology with those around the EPNP-reactive aspartyl residues in rennin (chymosin) [EC 3.4.23.4] and pepsin [EC 3.4.23.1]. The other peptide contained no methionine residue and gave the sequence: Asp-Thr-Gly-Thr-Thr-Leu. The N-terminal aspartyl residue of each peptide was deduced to be the EPNP-reactive site."}
{"id": "PMID:16880", "title": "Phosphoenolypyruvate synthetase of Escherichia coli: molecular weight, subunit composition, and identification of phosphohistidine in phosphoenzyme intermediate.", "content": "Phosphoenolypyruvate synthetase of Escherichia coli has been shown to be a dimer of molecular weight 150,000. The constituent subunits appear to be identical. The enzyme tends to dissociate to monomers at low protein concentration, but the tendency is much diminished in the phosphoenzyme form, suggesting that enzyme phosphorylation is accompanied by a structural rearrangement in the subunit contact domain. The enzyme appears to show half of the sites reactivity with respect to its phosphorylation by ATP. Several lines of evidence, including identification of 3-phosphohistidine in alkaline digests of the phosphoenzyme, indicate that a histidyl residue is the site of phosphorylation.", "contents": "Phosphoenolypyruvate synthetase of Escherichia coli: molecular weight, subunit composition, and identification of phosphohistidine in phosphoenzyme intermediate. Phosphoenolypyruvate synthetase of Escherichia coli has been shown to be a dimer of molecular weight 150,000. The constituent subunits appear to be identical. The enzyme tends to dissociate to monomers at low protein concentration, but the tendency is much diminished in the phosphoenzyme form, suggesting that enzyme phosphorylation is accompanied by a structural rearrangement in the subunit contact domain. The enzyme appears to show half of the sites reactivity with respect to its phosphorylation by ATP. Several lines of evidence, including identification of 3-phosphohistidine in alkaline digests of the phosphoenzyme, indicate that a histidyl residue is the site of phosphorylation."}
{"id": "PMID:16881", "title": "Source of residual Bohr effect in hemoglobin oxidation.", "content": "The hemoglobin oxidation Bohr effect is larger than the ligation Bohr effect, even when the former is corrected for any ionization of the water molecule bound to the ferric iron of methemoglobin. This residual oxidation Bohr effect is here shown to be solely caused by the influence of the positively charged ferriheme, and is abolished when the oxidized heme binds an anion. This result frees the formal equivalence of hemoglobin ligation and oxidation from the last apparent experimental discrepancy.", "contents": "Source of residual Bohr effect in hemoglobin oxidation. The hemoglobin oxidation Bohr effect is larger than the ligation Bohr effect, even when the former is corrected for any ionization of the water molecule bound to the ferric iron of methemoglobin. This residual oxidation Bohr effect is here shown to be solely caused by the influence of the positively charged ferriheme, and is abolished when the oxidized heme binds an anion. This result frees the formal equivalence of hemoglobin ligation and oxidation from the last apparent experimental discrepancy."}
{"id": "PMID:16883", "title": "Magnetic resonance studies of concanavalin A: assignment of histidine resonances in 220 MHz proton spectrum of complexes with Co2+ and Zn2+.", "content": "The low field regions of the 220 MHz proton magnetic resonance spectra of concanavalin A (Con A) complexes with metal ions show well resolved resonances from the C2 protons of histidine side chains. Shifts of these resonances are observed when Zn2+ ions at the transition metal ion binding site, S1, are replaced by CO2 ions. The magnitude of these shifts can be used to determine the orientation of axis of anisotropy of the Co2+ ligand field since the distances from the C2 protons of the histidines to S1 can be computed from the crystal structure coordinates. Assignment of the separate peaks in the spectrum of the Con A-Co2+-Ca2+ complex and of the Con A-Zn2+-Ca2+ complex, to particular histidines in the amino acid sequence of Con A then follows. The refined crystal coordinates of both Reeke et al. (Reeke, G. N., Jr., Becker, J. W., and Edelman, G. M. (1975) J. Biol. Chem, 250, 1525-1547) and of Hardman and Ainsworth (private communication) have been used. These two sets of coordinates both yield orientations for the axis of anisotropy which are approximately in the direction of the His 24 nitrogen ligand.", "contents": "Magnetic resonance studies of concanavalin A: assignment of histidine resonances in 220 MHz proton spectrum of complexes with Co2+ and Zn2+. The low field regions of the 220 MHz proton magnetic resonance spectra of concanavalin A (Con A) complexes with metal ions show well resolved resonances from the C2 protons of histidine side chains. Shifts of these resonances are observed when Zn2+ ions at the transition metal ion binding site, S1, are replaced by CO2 ions. The magnitude of these shifts can be used to determine the orientation of axis of anisotropy of the Co2+ ligand field since the distances from the C2 protons of the histidines to S1 can be computed from the crystal structure coordinates. Assignment of the separate peaks in the spectrum of the Con A-Co2+-Ca2+ complex and of the Con A-Zn2+-Ca2+ complex, to particular histidines in the amino acid sequence of Con A then follows. The refined crystal coordinates of both Reeke et al. (Reeke, G. N., Jr., Becker, J. W., and Edelman, G. M. (1975) J. Biol. Chem, 250, 1525-1547) and of Hardman and Ainsworth (private communication) have been used. These two sets of coordinates both yield orientations for the axis of anisotropy which are approximately in the direction of the His 24 nitrogen ligand."}
{"id": "PMID:16885", "title": "Bovine adrenal tyrosine hydroxylase: purification and properties.", "content": "Bovine adrenal tyrosine hydroxylase has been obtained in a form that is 85 to 90% pure. Sodium dodecyl sulfate-gel electrophoresis and density gradient centrifugation studies have established that the subunit molecular weight of the chymotrypsin-solubilized enzyme is 34,000. The presence of iron in the purified enzyme (0.50 to 0.75 mol of iron/mol of enzyme) has been established. Crude particulate tyrosine hydroxylase can be activated by the phospholipid, phosphatidyl-L-serine, or by exposure to enzymatic phosphorylating conditions. Both forms of activation lower the Km of the enzyme for its 2-amino-4-hydroxypteridine cofactor. By contrast, tyrosine hydroxylase that has been solubilized by chymotrypsin cannot be activated by either of these methods.", "contents": "Bovine adrenal tyrosine hydroxylase: purification and properties. Bovine adrenal tyrosine hydroxylase has been obtained in a form that is 85 to 90% pure. Sodium dodecyl sulfate-gel electrophoresis and density gradient centrifugation studies have established that the subunit molecular weight of the chymotrypsin-solubilized enzyme is 34,000. The presence of iron in the purified enzyme (0.50 to 0.75 mol of iron/mol of enzyme) has been established. Crude particulate tyrosine hydroxylase can be activated by the phospholipid, phosphatidyl-L-serine, or by exposure to enzymatic phosphorylating conditions. Both forms of activation lower the Km of the enzyme for its 2-amino-4-hydroxypteridine cofactor. By contrast, tyrosine hydroxylase that has been solubilized by chymotrypsin cannot be activated by either of these methods."}
{"id": "PMID:16888", "title": "Isolation of glutamic acid methyl ester from an Escherichia coli membrane protein involved in chemotaxis.", "content": "We have isolated glutamic acid 5-methyl ester from an Escherichia coli protein that is involved in chemotaxis. The bacteria were first incubated with [methyl-3H]methionine under conditions which are known to result in methylation of the protein. The protein, isolated by gel electrophoresis, was then digested by successive treatment with three proteolytic enzymes. One of the products was [methyl-3H]glutamic acid 5-methyl ester, identified by comparison with an authentic sample in the following studies: (a) chromatography on an automatic amino acid analyzer, (b) chromatography on paper in two solvent systems, (c) chromatography on paper of the N-acetyl derivatives, and (d) stability of the ester bond to various pH conditions. No aspartic acid 4-methyl ester was found in the enzymatic digest. Treatment of the methylated protein with alkali released the radioactivity as [3H]methanol, which was identified by gas chromatography and by preparation of the 3,5-dinitrobenzoate.", "contents": "Isolation of glutamic acid methyl ester from an Escherichia coli membrane protein involved in chemotaxis. We have isolated glutamic acid 5-methyl ester from an Escherichia coli protein that is involved in chemotaxis. The bacteria were first incubated with [methyl-3H]methionine under conditions which are known to result in methylation of the protein. The protein, isolated by gel electrophoresis, was then digested by successive treatment with three proteolytic enzymes. One of the products was [methyl-3H]glutamic acid 5-methyl ester, identified by comparison with an authentic sample in the following studies: (a) chromatography on an automatic amino acid analyzer, (b) chromatography on paper in two solvent systems, (c) chromatography on paper of the N-acetyl derivatives, and (d) stability of the ester bond to various pH conditions. No aspartic acid 4-methyl ester was found in the enzymatic digest. Treatment of the methylated protein with alkali released the radioactivity as [3H]methanol, which was identified by gas chromatography and by preparation of the 3,5-dinitrobenzoate."}
{"id": "PMID:16889", "title": "Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase in HeLa cells by glucocorticoids.", "content": "The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) has been demonstrated both in homogenates and microsomes of the S3G strain of HeLa cells. It was increased 8- to 10-fold by the removal of serum from the growth medium. The presence of steroids, specifically of the glucocorticoid series, in the serum-less growth medium elicited an additional 100 to 345% increase over the serum-less control, whereas the addition of N6,O2'-dibutyryl adenosine 3':5'-monophosphate to the medium or dexamethasone to the assay mixture was without any stimulatory effect. Both inductions were blocked by cycloheximide and actinomycin D, suggesting a protein synthesis-dependent elevation of enzyme activity. Glucocorticoids were effective in the induction at concentrations ranging from 10(-6) to 10(-8) M and there was a demonstrated parallel between the magnitude of enzyme induction and glucocorticoid potency. The HMG-CoA reductase activities from steroid-induced and control cultures had identical assay characteristics (pH optima and apparent Km values for both NADPH and HMG-CoA). This induction of the rate-controlling enzyme of cholesterogenesis occurred despite the observation that glucocorticoids specifically depress the rate of acetate or water, but not mevalonate, incorporation into cholesterol.", "contents": "Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase in HeLa cells by glucocorticoids. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) has been demonstrated both in homogenates and microsomes of the S3G strain of HeLa cells. It was increased 8- to 10-fold by the removal of serum from the growth medium. The presence of steroids, specifically of the glucocorticoid series, in the serum-less growth medium elicited an additional 100 to 345% increase over the serum-less control, whereas the addition of N6,O2'-dibutyryl adenosine 3':5'-monophosphate to the medium or dexamethasone to the assay mixture was without any stimulatory effect. Both inductions were blocked by cycloheximide and actinomycin D, suggesting a protein synthesis-dependent elevation of enzyme activity. Glucocorticoids were effective in the induction at concentrations ranging from 10(-6) to 10(-8) M and there was a demonstrated parallel between the magnitude of enzyme induction and glucocorticoid potency. The HMG-CoA reductase activities from steroid-induced and control cultures had identical assay characteristics (pH optima and apparent Km values for both NADPH and HMG-CoA). This induction of the rate-controlling enzyme of cholesterogenesis occurred despite the observation that glucocorticoids specifically depress the rate of acetate or water, but not mevalonate, incorporation into cholesterol."}
{"id": "PMID:16891", "title": "Purification and properties of a plant endonuclease specific for apurinic sites.", "content": "An endonuclease which hydrolyzes depurinated DNA has been isolated from Phaseolus multiflorus enbryos; it has a molecular weight around 40,000. The enzyme is specific for apurinic sites; it has no action on normal DNA strands or on alkylated sites, and is without exonulcease activity. The rate of phosphoester bond hydrolysis near apurinic sites is far greater in native than in denatured DNA. The endonuclease is not inactivated by 10 mM EDTA, but is activity is however stimulated by Mg2+ or Mn2+. Its optimum pH is 7.5 to 8.0, and its optimum temperature 40degrees although, at this temperature, it is rapidly denatured; even low NaCl concentrations inhibit the enzyme activity. The endonuclease for apurinic sites of P. multiflorus is a non-histone protein of chromatin; the properties (like thermosensitivity of susceptibility to ionic strength) of the enzyme in situ, working on chromatin DNA, might be different from those described for the isolated endonuclease in homogenous aqueous solution.", "contents": "Purification and properties of a plant endonuclease specific for apurinic sites. An endonuclease which hydrolyzes depurinated DNA has been isolated from Phaseolus multiflorus enbryos; it has a molecular weight around 40,000. The enzyme is specific for apurinic sites; it has no action on normal DNA strands or on alkylated sites, and is without exonulcease activity. The rate of phosphoester bond hydrolysis near apurinic sites is far greater in native than in denatured DNA. The endonuclease is not inactivated by 10 mM EDTA, but is activity is however stimulated by Mg2+ or Mn2+. Its optimum pH is 7.5 to 8.0, and its optimum temperature 40degrees although, at this temperature, it is rapidly denatured; even low NaCl concentrations inhibit the enzyme activity. The endonuclease for apurinic sites of P. multiflorus is a non-histone protein of chromatin; the properties (like thermosensitivity of susceptibility to ionic strength) of the enzyme in situ, working on chromatin DNA, might be different from those described for the isolated endonuclease in homogenous aqueous solution."}
{"id": "PMID:16892", "title": "Estrogen-binding protein from rat preputial gland: purification and characterization.", "content": "Cytosol from the rat preputial gland has been shown to contain a protein which binds both estrone and estradiol. The protein, after a 26-fold purification from the cytosol of female Sprague-Dawley rats, migrated as one band during electrophoresis in sodium dodecyl sulfate on acrylamide gel. The electrophoretic mobility indicated a molecular weight of 15,000. The association constant for estrone as determined by equilibrium dialysis was 1.2 X 10(7) M-1, while that for 17beta-estradiol was 3.3 X 10(6) M-1. Progesterone, cortisol, testosterone, or diethylstilbestrol did not bind to the purified protein, whereas 17alpha-estradiol or estriol bound only slightly. In the presence of retinoic acid, but not retinol, the binding of estrone was reduced. Optimum binding for estrone was at pH 6.5 to 8.5.", "contents": "Estrogen-binding protein from rat preputial gland: purification and characterization. Cytosol from the rat preputial gland has been shown to contain a protein which binds both estrone and estradiol. The protein, after a 26-fold purification from the cytosol of female Sprague-Dawley rats, migrated as one band during electrophoresis in sodium dodecyl sulfate on acrylamide gel. The electrophoretic mobility indicated a molecular weight of 15,000. The association constant for estrone as determined by equilibrium dialysis was 1.2 X 10(7) M-1, while that for 17beta-estradiol was 3.3 X 10(6) M-1. Progesterone, cortisol, testosterone, or diethylstilbestrol did not bind to the purified protein, whereas 17alpha-estradiol or estriol bound only slightly. In the presence of retinoic acid, but not retinol, the binding of estrone was reduced. Optimum binding for estrone was at pH 6.5 to 8.5."}
{"id": "PMID:16894", "title": "Properties of chitin synthetase in isolated chitosomes from yeast cells of Mucor rouxii.", "content": "Chitin synthetase was isolated and purified 120-fold from the supernatant fraction (54,500 X g) of broken yeast cells of Mucor rouxii. The purified preparations consisted mainly of chitin synthetase particles (chitosomes) with an average size larger than 7 X 10(6) daltons (by gel filtration) and an average sedimentation coefficient of 105 S. The samples also contained other enzyme complexes (fatty acid synthetase, pyruvate dehydrogenase, and, depending on method, ribosomes). Nearly all of the chitosomal chitin synthetase occurred in a zymogenic form that required proteolytic activation. In most properties, the chitosomal enzyme was similar to crude enzyme (54,000 X g sediment): kinetics, activation by proteases, response to metals, stimulation by N-acetylglucosamine, and inhibition by polyoxin or UDP. One mamor difference was the much greater stability of the chitosomal chitin synthetase zymogen against spontaneous activation and destruction. Product (chitin microfibril) and enzyme (chitin synthetase) remained associated in a complex that was readily separated by centrifugation.", "contents": "Properties of chitin synthetase in isolated chitosomes from yeast cells of Mucor rouxii. Chitin synthetase was isolated and purified 120-fold from the supernatant fraction (54,500 X g) of broken yeast cells of Mucor rouxii. The purified preparations consisted mainly of chitin synthetase particles (chitosomes) with an average size larger than 7 X 10(6) daltons (by gel filtration) and an average sedimentation coefficient of 105 S. The samples also contained other enzyme complexes (fatty acid synthetase, pyruvate dehydrogenase, and, depending on method, ribosomes). Nearly all of the chitosomal chitin synthetase occurred in a zymogenic form that required proteolytic activation. In most properties, the chitosomal enzyme was similar to crude enzyme (54,000 X g sediment): kinetics, activation by proteases, response to metals, stimulation by N-acetylglucosamine, and inhibition by polyoxin or UDP. One mamor difference was the much greater stability of the chitosomal chitin synthetase zymogen against spontaneous activation and destruction. Product (chitin microfibril) and enzyme (chitin synthetase) remained associated in a complex that was readily separated by centrifugation."}
{"id": "PMID:16896", "title": "DNA polymerase of mitochondria is a gamma-polymerase.", "content": "Mitochondria isolated from rat liver cells or mycoplasma-free HeLa cells contain a single DNA polymerase activity which is closely related to, or identical to, the DNA polymerase gamma activity found in the homologous cell. In rat liver cells, about 16% of the total cytoplasmic gamma-polymerase activity is found associated with mitochondria and in HeLa cells about 20% of the total cellular gamma-polymerase is mitochondria associated. Since mitochondria possess no unique DNA polymerase activity, the number of DNA polymerases now known in mammalian cells is reduced, from the previously proposed four enzymes, to three--DNA polymerases alpha, beta, and gamma.", "contents": "DNA polymerase of mitochondria is a gamma-polymerase. Mitochondria isolated from rat liver cells or mycoplasma-free HeLa cells contain a single DNA polymerase activity which is closely related to, or identical to, the DNA polymerase gamma activity found in the homologous cell. In rat liver cells, about 16% of the total cytoplasmic gamma-polymerase activity is found associated with mitochondria and in HeLa cells about 20% of the total cellular gamma-polymerase is mitochondria associated. Since mitochondria possess no unique DNA polymerase activity, the number of DNA polymerases now known in mammalian cells is reduced, from the previously proposed four enzymes, to three--DNA polymerases alpha, beta, and gamma."}
{"id": "PMID:16897", "title": "Characterization of plasma membrane adenosine triphosphatase of Neurospora crassa.", "content": "It has been proposed (Slayman, C.L., Long W.S., and Lu, C.Y.-H. (1973) J. Membr. Biol. 14, 305--338) that in Neurospora crassa, a plasma membrane ATPase functions to pump H+ ions out of the cell, thereby generating an electrochemical gradient that can drive transport processes. Using the concanavalin A method of Scarborough (Scarborough G.A. (1975)J. Biol. Chem. 250, 1106--1111), we have prepared plasma membranes of Neurospora and have deomonstrated that they do contain a distinct ATPase activity with the following properties. It has a pH optimum of 6.0, is highly specific for ATP (hydrolyzing other nucleoside triphosphates less than 6% as rapidly), requires Mg2+ at concentrations approximately equimolar to the concentration of ATP, is weakly stimulated by certain monovalent cations (K+ and NH4+) and anions (SCN- and acetate), is inhibited by N,N'-dicyclohexylcarbodiimide, but is not affected by oligomycin or ouabain. The plasma membrane fraction also contains residual mitochondrial contamination, which can be determined quantitatively by assaying oligomycin-sensitive ATP-ase activity, at pH 8.25, and succinic dehydrogenase activity.", "contents": "Characterization of plasma membrane adenosine triphosphatase of Neurospora crassa. It has been proposed (Slayman, C.L., Long W.S., and Lu, C.Y.-H. (1973) J. Membr. Biol. 14, 305--338) that in Neurospora crassa, a plasma membrane ATPase functions to pump H+ ions out of the cell, thereby generating an electrochemical gradient that can drive transport processes. Using the concanavalin A method of Scarborough (Scarborough G.A. (1975)J. Biol. Chem. 250, 1106--1111), we have prepared plasma membranes of Neurospora and have deomonstrated that they do contain a distinct ATPase activity with the following properties. It has a pH optimum of 6.0, is highly specific for ATP (hydrolyzing other nucleoside triphosphates less than 6% as rapidly), requires Mg2+ at concentrations approximately equimolar to the concentration of ATP, is weakly stimulated by certain monovalent cations (K+ and NH4+) and anions (SCN- and acetate), is inhibited by N,N'-dicyclohexylcarbodiimide, but is not affected by oligomycin or ouabain. The plasma membrane fraction also contains residual mitochondrial contamination, which can be determined quantitatively by assaying oligomycin-sensitive ATP-ase activity, at pH 8.25, and succinic dehydrogenase activity."}
{"id": "PMID:16898", "title": "Identification of folate binding macromolecule in rabbit choroid plexus.", "content": "A macromolecular binder of folic acid and folic acid derivatives has been identified in the particulate fraction of homogenates of rabbit choroid plexus. Within the choroid plexus, there are 2.3 nmol of folate-binding activity (binder) per g of tissue. The molecular weight of the folate binder complex, separated from the particulate fraction after solubilization with Triton X-100, was 340,000 to 400,000 by Sephadex gel filtration. The partially purified binder, when freed of endogenous folates, bound equivalent amounts of both [3H]folic acid and [methyl-14C]methyltetrahydrofolic acid per mg of protein. Folic acid, homofolic acid, 5-methyltetrahydrofolic acid, and to a lesser degree, methotrexate, inhibited the binding of both [3H]folic acid and [14C]methyltetrahydrofolic acid. Binding activity, which decreased below pH = 7.0, was unaffected by pretreatment with ribonuclease but was eliminated completely by papain and a protease (Streptomyces griseus). Although dihydrofolate reductase was present in choroid plexus, the binder was distinct from dihydrofolate reductase as judged by gel filtration and methotrexate sensitivity. This high affinity binder of folates may be responsible, in part, for the rapid, saturable uptake of folic acid and methyltetrahydrofolic acid by rabbit choroid plexus in vitro.", "contents": "Identification of folate binding macromolecule in rabbit choroid plexus. A macromolecular binder of folic acid and folic acid derivatives has been identified in the particulate fraction of homogenates of rabbit choroid plexus. Within the choroid plexus, there are 2.3 nmol of folate-binding activity (binder) per g of tissue. The molecular weight of the folate binder complex, separated from the particulate fraction after solubilization with Triton X-100, was 340,000 to 400,000 by Sephadex gel filtration. The partially purified binder, when freed of endogenous folates, bound equivalent amounts of both [3H]folic acid and [methyl-14C]methyltetrahydrofolic acid per mg of protein. Folic acid, homofolic acid, 5-methyltetrahydrofolic acid, and to a lesser degree, methotrexate, inhibited the binding of both [3H]folic acid and [14C]methyltetrahydrofolic acid. Binding activity, which decreased below pH = 7.0, was unaffected by pretreatment with ribonuclease but was eliminated completely by papain and a protease (Streptomyces griseus). Although dihydrofolate reductase was present in choroid plexus, the binder was distinct from dihydrofolate reductase as judged by gel filtration and methotrexate sensitivity. This high affinity binder of folates may be responsible, in part, for the rapid, saturable uptake of folic acid and methyltetrahydrofolic acid by rabbit choroid plexus in vitro."}
{"id": "PMID:16900", "title": "Repressible alkaline phosphatase from Thermus aquaticus: associated phosphodiesterase activity.", "content": "A repressible alkaline phosphatase has been isolated from the extreme bacterial thermophile. Thermus aquaticus, and has been purified to homogeneity as judged by disc acrylamide electrophoresis and sodium dodecyl sulfate electrophoresis. Upon investigation, the purified enzyme was shown to hydrolyze certain phosphodiesters in addition to a wide variety of phosphomonoesters. The diesters included bis-p-nitro-phenyl phosphate and thymidine 3'-monophospho-p-nitro-phenyl ester. The temperature optimum for the diesterase activity was 80--85 degrees at pH 7.2. Orthophosphate competitively inhibited both activities. Nucleotides such as AMP, ADP, and ATP also inhibited both esterase activities as did alpha-D-glucose 1-phosphate and alpha-sodium glycerol phosphate. The isoelectric point of the enzyme was determined to be 8.4.", "contents": "Repressible alkaline phosphatase from Thermus aquaticus: associated phosphodiesterase activity. A repressible alkaline phosphatase has been isolated from the extreme bacterial thermophile. Thermus aquaticus, and has been purified to homogeneity as judged by disc acrylamide electrophoresis and sodium dodecyl sulfate electrophoresis. Upon investigation, the purified enzyme was shown to hydrolyze certain phosphodiesters in addition to a wide variety of phosphomonoesters. The diesters included bis-p-nitro-phenyl phosphate and thymidine 3'-monophospho-p-nitro-phenyl ester. The temperature optimum for the diesterase activity was 80--85 degrees at pH 7.2. Orthophosphate competitively inhibited both activities. Nucleotides such as AMP, ADP, and ATP also inhibited both esterase activities as did alpha-D-glucose 1-phosphate and alpha-sodium glycerol phosphate. The isoelectric point of the enzyme was determined to be 8.4."}
{"id": "PMID:16904", "title": "Specificity of 2-keto-3-deoxygluconate-6-P aldolase for open chain form of 2-keto-3-deoxygluconate-6-P.", "content": "2-Keto-3-deoxygluconate-6-P exists as an euqilibrium of three forms at 25 degrees measurable by 13C NMR: alpha-furanose anomer (41%), beta-furanose anomer (50%), and open chain keto (9%). The three forms are interconverted rapidly (greater than 0.5 s-1) so that the unidirectional rates of furanose ring opening and closing can be quantitated by an NMR line broadening method. The 2-keto-3-deoxygluconate aldolase is specific for only one of these forms, the open chain keto form. The rates for ring opening calculated from the rapid kinetic enzyme system compare closely with those obtained with the NMR method.", "contents": "Specificity of 2-keto-3-deoxygluconate-6-P aldolase for open chain form of 2-keto-3-deoxygluconate-6-P. 2-Keto-3-deoxygluconate-6-P exists as an euqilibrium of three forms at 25 degrees measurable by 13C NMR: alpha-furanose anomer (41%), beta-furanose anomer (50%), and open chain keto (9%). The three forms are interconverted rapidly (greater than 0.5 s-1) so that the unidirectional rates of furanose ring opening and closing can be quantitated by an NMR line broadening method. The 2-keto-3-deoxygluconate aldolase is specific for only one of these forms, the open chain keto form. The rates for ring opening calculated from the rapid kinetic enzyme system compare closely with those obtained with the NMR method."}
{"id": "PMID:16907", "title": "Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase.", "content": "Methoxypolyethylene glycols of 1900 daltons (PEG-1900) or 5000 daltons (PEG-5000) were covalently attached to bovine liver catalase using 2,4,6-trichloro-s-triazine as the coupling agent. Rabbits were immunized by the intravenous and intramuscular routes with catalase modified by covalent attachment of PEG-1900 to 43% of the amino groups (PEG-1900-catalase). The intravenous antiserum did not yield detectable antibodies against PEG-1900-catalase or native catalase, as determined by Ouchterlony and complement fixation methods, whereas the intramuscular antiserum contained antibodies to both PEG-1900-catalase and catalase. PEG-1900 did not react with either antiserum. Catalase was prepared in which PEG-5000 was attached to 40% of the amino groups (PEG-5000-catalase). This catalase preparation did not react with either antiserum. PEG-1900-catalase retained 93% of its enzymatic activity; PEG-5000-catalase retained 95%. PEG-5000-catalase resisted digestion by trypsin, chymotrypsin, and a protease from Streptomyces griseus. PEG-1900-catalase and PEG-5000-catalase exhibited enhanced circulating lives in the blood of acatalasemic mice during repetitive intravenous injections. No evidence was seen of an immune response to injections of the modified enzymes. Mice injected repetitively with PEG-5000-catalase remained immune competent for unmodieied catalase, and no evidence of tissue or organ damage was seen.", "contents": "Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. Methoxypolyethylene glycols of 1900 daltons (PEG-1900) or 5000 daltons (PEG-5000) were covalently attached to bovine liver catalase using 2,4,6-trichloro-s-triazine as the coupling agent. Rabbits were immunized by the intravenous and intramuscular routes with catalase modified by covalent attachment of PEG-1900 to 43% of the amino groups (PEG-1900-catalase). The intravenous antiserum did not yield detectable antibodies against PEG-1900-catalase or native catalase, as determined by Ouchterlony and complement fixation methods, whereas the intramuscular antiserum contained antibodies to both PEG-1900-catalase and catalase. PEG-1900 did not react with either antiserum. Catalase was prepared in which PEG-5000 was attached to 40% of the amino groups (PEG-5000-catalase). This catalase preparation did not react with either antiserum. PEG-1900-catalase retained 93% of its enzymatic activity; PEG-5000-catalase retained 95%. PEG-5000-catalase resisted digestion by trypsin, chymotrypsin, and a protease from Streptomyces griseus. PEG-1900-catalase and PEG-5000-catalase exhibited enhanced circulating lives in the blood of acatalasemic mice during repetitive intravenous injections. No evidence was seen of an immune response to injections of the modified enzymes. Mice injected repetitively with PEG-5000-catalase remained immune competent for unmodieied catalase, and no evidence of tissue or organ damage was seen."}
{"id": "PMID:16908", "title": "Human thrombins. Production, evaluation, and properties of alpha-thrombin.", "content": "Human alpha-thrombin, the thromboplastin activation product of prothrombin with high clotting and esterase activity, was produced from Cohn Fraction III paste. The procedure started with 0.4 to 3.2 kg of frozen paste and was completed in 2 or 3 days. Some 23 g of thrombin were recorded for 65 quantitated preparations made from 11 lots of Fraction III paste. These preparations were obtained at protein concentrations of 3.9 +/- 1.3 mg/ml with a yield of 340 +/- 110 mg/kg of paste, which represented 48 +/- 14% of the clotting potential extracted as prothrombin. They had specific clotting activities of 2.8 +/- 0.4 U.S. (NIH) units/microng of protein and titrated to 88 +/- 8% active with p-nitrophenyl-p'-guanidinobenzoate (NPGB). Those (N - 29) examined by labeling with [14C]diisopropyl phosphorofluoridate (iPr2P-F) and electrophoresing in sodium dodecyl sulfate (SDS)-polyacrylamide gels were found to contain only (N = 4) or predominantly alpha-thrombin (97 +/- 3%) and corresponding amounts of ists degradation product, beta-thrombin (2.6 +/- 3.1%). No plasmin(ogen), prothrombin complex factors (II, VII, IX, IXalpha, X, Xalpha), or prothrombin fragments were detected in representative preparations. As produced in 0.75 M NaCl, pH approximately 6, thrombin was stable for approximately 1 week at 4 degrees and for greater than 1 year at less than or equal to 50 degrees; freeze-dried thrombin stored at 4 degrees for greater than 1 year displayed stable clotting activity and no vial to vial variation, permitting its use for reference purposes. Human thrombin generated by Taipan snake venom activation was compared with that produced by rapid thromboplastin activation: after treatment with [14C]iPr2P-F, greater than 95% of the label in both thrombins migrated at the same rate during electrophoresis in SDS; identical pairs of NH2-terminal residues were released in three consecutive Edman degradation cycles.", "contents": "Human thrombins. Production, evaluation, and properties of alpha-thrombin. Human alpha-thrombin, the thromboplastin activation product of prothrombin with high clotting and esterase activity, was produced from Cohn Fraction III paste. The procedure started with 0.4 to 3.2 kg of frozen paste and was completed in 2 or 3 days. Some 23 g of thrombin were recorded for 65 quantitated preparations made from 11 lots of Fraction III paste. These preparations were obtained at protein concentrations of 3.9 +/- 1.3 mg/ml with a yield of 340 +/- 110 mg/kg of paste, which represented 48 +/- 14% of the clotting potential extracted as prothrombin. They had specific clotting activities of 2.8 +/- 0.4 U.S. (NIH) units/microng of protein and titrated to 88 +/- 8% active with p-nitrophenyl-p'-guanidinobenzoate (NPGB). Those (N - 29) examined by labeling with [14C]diisopropyl phosphorofluoridate (iPr2P-F) and electrophoresing in sodium dodecyl sulfate (SDS)-polyacrylamide gels were found to contain only (N = 4) or predominantly alpha-thrombin (97 +/- 3%) and corresponding amounts of ists degradation product, beta-thrombin (2.6 +/- 3.1%). No plasmin(ogen), prothrombin complex factors (II, VII, IX, IXalpha, X, Xalpha), or prothrombin fragments were detected in representative preparations. As produced in 0.75 M NaCl, pH approximately 6, thrombin was stable for approximately 1 week at 4 degrees and for greater than 1 year at less than or equal to 50 degrees; freeze-dried thrombin stored at 4 degrees for greater than 1 year displayed stable clotting activity and no vial to vial variation, permitting its use for reference purposes. Human thrombin generated by Taipan snake venom activation was compared with that produced by rapid thromboplastin activation: after treatment with [14C]iPr2P-F, greater than 95% of the label in both thrombins migrated at the same rate during electrophoresis in SDS; identical pairs of NH2-terminal residues were released in three consecutive Edman degradation cycles."}
{"id": "PMID:16910", "title": "Interaction of apoA-II from human high density lipoprotein with lysolecithin.", "content": "The effects of lysolecithin and hexadecyltrimethylammonium bromide on the structure and stability of apoA-II from human high density lipoprotein have been evalued by circular dichroism and fluorescence measurements. There is a profound enhancement in the stability of apoA-II to guanidinium hydrochloride denaturation when it forms a phospholipid complex with lysolecithin micelles. This complex is not only resistant to guanidinium hydrochloride denaturation, but it can be formed in a 6 M solution of this denaturant. The behavior of apoA-II in the native human high density protein is much closer to that of the lysolecithin apoA-II complex than to that of the free apoA-II.", "contents": "Interaction of apoA-II from human high density lipoprotein with lysolecithin. The effects of lysolecithin and hexadecyltrimethylammonium bromide on the structure and stability of apoA-II from human high density lipoprotein have been evalued by circular dichroism and fluorescence measurements. There is a profound enhancement in the stability of apoA-II to guanidinium hydrochloride denaturation when it forms a phospholipid complex with lysolecithin micelles. This complex is not only resistant to guanidinium hydrochloride denaturation, but it can be formed in a 6 M solution of this denaturant. The behavior of apoA-II in the native human high density protein is much closer to that of the lysolecithin apoA-II complex than to that of the free apoA-II."}
{"id": "PMID:16912", "title": "Liver microsomal epoxide hydrase.", "content": "1. The substrate specificity of membrane-bound and purified epoxide hydrase from rat liver microsomes has been studied. Both enzyme preparations catalyzed the hydration of a variety of alkene oxidase as well as arene oxides of several polycyclic aromatic hydrocarbons. 2. Unlike the membrane-bound enzyme, the rate of hydration for most of the substrates catalyzed by the purified epoxide hydrase was constant for only 1 or 2 min. The addition of dilauroyl phosphatidylcholine or heated microsomes to the incubation mixture extended the linearity of the reaction. 3. When rat liver microsomes were used as the source of the enzyme, the apparent Km values for many of the substrates were dependent on the amount of microsomes used. When purified epoxide hydrase was used as the enzyme source and benzo(a)pyrene 11,12-oxide as substrate, the apparent Km for benzo(a)pyrene 11,12-oxide was independent of enzyme concentration but dependent on added lipid concentration. Thus, in the absence of added dilauroyl phosphatidylcholine or in the presence of this lipid at a concentration below its critical micelle concentration, the observed Km for benzo(a)pyrene 11,12-oxide remained constant. However, when the lipid concentration was greater than the critical micelle concentration, the apparent Km value increased linearly with lipid concentration. These results are consistent with a model based on the partition of lipid-soluble substrate between the lipid micelle and the aqueous medium.", "contents": "Liver microsomal epoxide hydrase. 1. The substrate specificity of membrane-bound and purified epoxide hydrase from rat liver microsomes has been studied. Both enzyme preparations catalyzed the hydration of a variety of alkene oxidase as well as arene oxides of several polycyclic aromatic hydrocarbons. 2. Unlike the membrane-bound enzyme, the rate of hydration for most of the substrates catalyzed by the purified epoxide hydrase was constant for only 1 or 2 min. The addition of dilauroyl phosphatidylcholine or heated microsomes to the incubation mixture extended the linearity of the reaction. 3. When rat liver microsomes were used as the source of the enzyme, the apparent Km values for many of the substrates were dependent on the amount of microsomes used. When purified epoxide hydrase was used as the enzyme source and benzo(a)pyrene 11,12-oxide as substrate, the apparent Km for benzo(a)pyrene 11,12-oxide was independent of enzyme concentration but dependent on added lipid concentration. Thus, in the absence of added dilauroyl phosphatidylcholine or in the presence of this lipid at a concentration below its critical micelle concentration, the observed Km for benzo(a)pyrene 11,12-oxide remained constant. However, when the lipid concentration was greater than the critical micelle concentration, the apparent Km value increased linearly with lipid concentration. These results are consistent with a model based on the partition of lipid-soluble substrate between the lipid micelle and the aqueous medium."}
{"id": "PMID:16913", "title": "Acidic dissociation constants of folic acid, dihydrofolic acid, and methotrexate.", "content": "The acidic dissociation constants in the range HO--1.5 to pH 7 of folic acid, dihydrofolic acid, methopterin (N(10)methylfolic acid), and methotrexate have been measured by potentiometric and spectrophotometric titrations. Assignment of these dissociations was made by comparison to model compounds, by proton magnetic resonance measurements, and by examination of associated ultraviolet absorbance changes. For folic acid, the dissociation constants are as follows: N(1), pK' 2.35; N(10), pK' 0.20; N(5), pK' greater than -1.5. For dihydrofolic acid: N(5), pK' 3.84; N(1), pK' 1.38; N(10), pK' 0.28. For methotrexate: N(1), pK' 5.71; gamma-carboxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5), boxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5) pK' greater than -1.5. For methopterin: acidic ionization of amide, pK' 7.68; gamma-carboxyl, pK' 4.62; N(1), pK' 2.40; N(10), pK; 0.36; N(5), pK' greater than -1.5. The pK' values were determined directly for the four compounds at 25 degrees near 0.1 ionic strength, or in 0.1 to 4 M HCl for pK ln 0.1 M NaCl.", "contents": "Acidic dissociation constants of folic acid, dihydrofolic acid, and methotrexate. The acidic dissociation constants in the range HO--1.5 to pH 7 of folic acid, dihydrofolic acid, methopterin (N(10)methylfolic acid), and methotrexate have been measured by potentiometric and spectrophotometric titrations. Assignment of these dissociations was made by comparison to model compounds, by proton magnetic resonance measurements, and by examination of associated ultraviolet absorbance changes. For folic acid, the dissociation constants are as follows: N(1), pK' 2.35; N(10), pK' 0.20; N(5), pK' greater than -1.5. For dihydrofolic acid: N(5), pK' 3.84; N(1), pK' 1.38; N(10), pK' 0.28. For methotrexate: N(1), pK' 5.71; gamma-carboxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5), boxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5) pK' greater than -1.5. For methopterin: acidic ionization of amide, pK' 7.68; gamma-carboxyl, pK' 4.62; N(1), pK' 2.40; N(10), pK; 0.36; N(5), pK' greater than -1.5. The pK' values were determined directly for the four compounds at 25 degrees near 0.1 ionic strength, or in 0.1 to 4 M HCl for pK ln 0.1 M NaCl."}
{"id": "PMID:16914", "title": "Protein modification enzymes associated with the protein-synthesizing complex from rabbit reticulocytes. Protein kinase, phosphoprotein phosphatase, and acetyltransferase.", "content": "A number of protein modification activities are present in the protein-synthesizing complex isolated from rabbit reticulocytes. These enzymes are solubilized by sedimentation of the ribosomes through buffered sucrose containing 0.5 M KCl, and have been partially purified from the high salt wash fraction by chromatography on DEAE-cellulose and phosphocellulose. The ribosomal-associated enzymatic activities include cyclic AMP-regulated and cyclic nucloetide-independent protein kinase, phosphoprotein phosphatase, and acetyltransferase activities. These enzymatic activities have been shown to modify specific ribosomal and ribosomal-associated proteins. The cycli c AMP-regulated protein kinase phosphorylate the 40 S ribosomal subunit from rabbit reticulocytes. One of the cyclic nucleotide-independent protein kinase catalyzes the phosphorylation of two different factors involved in the initiation of hemoglobin synthesis. A single phosphoprotein phosphatase activity is shown to remove phosphate from 40 S ribosomal subunits. The major acetyltransferase activity associated with ribosomes acetylates a 60 S ribosomal protein.", "contents": "Protein modification enzymes associated with the protein-synthesizing complex from rabbit reticulocytes. Protein kinase, phosphoprotein phosphatase, and acetyltransferase. A number of protein modification activities are present in the protein-synthesizing complex isolated from rabbit reticulocytes. These enzymes are solubilized by sedimentation of the ribosomes through buffered sucrose containing 0.5 M KCl, and have been partially purified from the high salt wash fraction by chromatography on DEAE-cellulose and phosphocellulose. The ribosomal-associated enzymatic activities include cyclic AMP-regulated and cyclic nucloetide-independent protein kinase, phosphoprotein phosphatase, and acetyltransferase activities. These enzymatic activities have been shown to modify specific ribosomal and ribosomal-associated proteins. The cycli c AMP-regulated protein kinase phosphorylate the 40 S ribosomal subunit from rabbit reticulocytes. One of the cyclic nucleotide-independent protein kinase catalyzes the phosphorylation of two different factors involved in the initiation of hemoglobin synthesis. A single phosphoprotein phosphatase activity is shown to remove phosphate from 40 S ribosomal subunits. The major acetyltransferase activity associated with ribosomes acetylates a 60 S ribosomal protein."}
{"id": "PMID:16917", "title": "Purification and properties of a membrane-associated, folate-binding protein from Lactobacillus casei.", "content": "A folate-binding protein has been solubilized from Lactobacillus casei by treatment of membrane preparations with Triton X-100 in the presence of [3H]folate. The protein-folate complex was purified 100-fold and recovered in a 22% yield by adsorption and elution from microgranular silica (Quso G-32), followed by passage through Sephadex G-150. When subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the purified preparations showed only a single, protein-staining band whose molecular weight was 25,000. Bound folate (34 nmol/mg of protein) corresponded to 0.85 mol/mol of protein. Analyses of the protein revealed relatively few charged or polar amino acids, an unusually high content of hydrophobic residues and methionine, and the absence of cysteine. The purified protein-folate complex was contained within a Triton micelle (molecular weight, 220,000; about 340 mol of detergent per mol of protein). Bound folate was retained when the micelle was exposed at 4 degrees to solutions whose pH values ranged between 3 and 12; at 23 degrees, however, stability was decreased, especially above pH 8. Folate could be released by treatment of the micelle with ethanol or with chaotropic agents such as guanidinium chloride, perchlorate, or thiocyanate.", "contents": "Purification and properties of a membrane-associated, folate-binding protein from Lactobacillus casei. A folate-binding protein has been solubilized from Lactobacillus casei by treatment of membrane preparations with Triton X-100 in the presence of [3H]folate. The protein-folate complex was purified 100-fold and recovered in a 22% yield by adsorption and elution from microgranular silica (Quso G-32), followed by passage through Sephadex G-150. When subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the purified preparations showed only a single, protein-staining band whose molecular weight was 25,000. Bound folate (34 nmol/mg of protein) corresponded to 0.85 mol/mol of protein. Analyses of the protein revealed relatively few charged or polar amino acids, an unusually high content of hydrophobic residues and methionine, and the absence of cysteine. The purified protein-folate complex was contained within a Triton micelle (molecular weight, 220,000; about 340 mol of detergent per mol of protein). Bound folate was retained when the micelle was exposed at 4 degrees to solutions whose pH values ranged between 3 and 12; at 23 degrees, however, stability was decreased, especially above pH 8. Folate could be released by treatment of the micelle with ethanol or with chaotropic agents such as guanidinium chloride, perchlorate, or thiocyanate."}
{"id": "PMID:16919", "title": "Purification and properties of NADPH-dependent aldehyde reductase from human liver.", "content": "An aldehyde reductase (EC 1.1.1.2) from human liver has been purified to homogeneity. The enzyme is NADPH-dependent, prefers aromatic to aliphatic aldehydes as substrates, and is inhibited by barbiturates and hydantoins. The following physicochemical parameters were determined: molecular weight, 36,200; sedimentation coefficient, 2.9 S; Stokes radius, 2.65 nm; isoelectric point, pH 5.3; extinction coefficient at 280 nm, 54,300 M-1 cm-1. Results from polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, gel filtration, and ultracentrifugation suggest a monomeric structure. On molecule of NADPH binds to the enzyme causing a red shift of the coenzyme absorption maximum from 340 to 352 nm. The amino acid composition has been determined and a partial specific volume of 0.74 was computed from these data. An alpha-helicity of 7 and 18% was estimated from the ellipticities at 208 and 222 nm, respectively. Combination of the most reactive thiol group with p-mercuribenzoate does not cause loss of catalytic activity. Inactivation occurs when more than one thiol group is modified. The presence of NADPH or NADP+ prevents loss of activity by thiol modification. The comparison of structural features of aldehyde reductase with other monomeric and oligomeric dehydrogenases suggest similarities of aldehyde reductase with octopine dehydrogenase.", "contents": "Purification and properties of NADPH-dependent aldehyde reductase from human liver. An aldehyde reductase (EC 1.1.1.2) from human liver has been purified to homogeneity. The enzyme is NADPH-dependent, prefers aromatic to aliphatic aldehydes as substrates, and is inhibited by barbiturates and hydantoins. The following physicochemical parameters were determined: molecular weight, 36,200; sedimentation coefficient, 2.9 S; Stokes radius, 2.65 nm; isoelectric point, pH 5.3; extinction coefficient at 280 nm, 54,300 M-1 cm-1. Results from polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, gel filtration, and ultracentrifugation suggest a monomeric structure. On molecule of NADPH binds to the enzyme causing a red shift of the coenzyme absorption maximum from 340 to 352 nm. The amino acid composition has been determined and a partial specific volume of 0.74 was computed from these data. An alpha-helicity of 7 and 18% was estimated from the ellipticities at 208 and 222 nm, respectively. Combination of the most reactive thiol group with p-mercuribenzoate does not cause loss of catalytic activity. Inactivation occurs when more than one thiol group is modified. The presence of NADPH or NADP+ prevents loss of activity by thiol modification. The comparison of structural features of aldehyde reductase with other monomeric and oligomeric dehydrogenases suggest similarities of aldehyde reductase with octopine dehydrogenase."}
{"id": "PMID:16920", "title": "Species-specific aggregation factor in sponges. Sialyltransferase associated with aggregation factor.", "content": "The sialyltransferase (= glycoprotein-sialic acid transferase) was studied in the sponge Geodia cydonium, a mesozoan organism. The experiments were performed both in intact cellular and in isolated enzyme systems. It is shown, that desialylated cells show a lower aggregation potency than the controls. During aggregation enzymic sialylation of desialylated sponge cells occurs in the presence of an aggregation factor, which is associated with a high molecular weight particle. The sialylation process is temperature-dependent and can be inhibited by N-ethylmaleimide. Sialylation occurs predominantly at a distinct cell surface component, the aggregation receptor. The sialyltransferase was isolated and purified by the following steps: Sepharose 4B, CM-cellulose, Nonidet treatment, and Sephadex G-100. By this procedure the enzyme was purified 680-fold with a 31% yield. The sialyltransferase is originally associated with the high molecular weight particle also carrying the aggregation factor. In the last step the aggregation factor was separated from the sialyltransferase. The enzyme catalyzes the transfer of sialic acid from CMP-sialic acid to the desialylated aggregation receptor. The molecular weight of the sialyltransferase has been determined to be 52,000. Kinetic studies revealed no lag phase and a dependence on enzyme concentration. The purified transferase has a pH optimum of 7.75 and requires 200 mM NaCl for activity. No requirement for Mg2+ or Ca2+ could be observed. The reaction is inhibited by 10 micronM N-ethylmaleimide.", "contents": "Species-specific aggregation factor in sponges. Sialyltransferase associated with aggregation factor. The sialyltransferase (= glycoprotein-sialic acid transferase) was studied in the sponge Geodia cydonium, a mesozoan organism. The experiments were performed both in intact cellular and in isolated enzyme systems. It is shown, that desialylated cells show a lower aggregation potency than the controls. During aggregation enzymic sialylation of desialylated sponge cells occurs in the presence of an aggregation factor, which is associated with a high molecular weight particle. The sialylation process is temperature-dependent and can be inhibited by N-ethylmaleimide. Sialylation occurs predominantly at a distinct cell surface component, the aggregation receptor. The sialyltransferase was isolated and purified by the following steps: Sepharose 4B, CM-cellulose, Nonidet treatment, and Sephadex G-100. By this procedure the enzyme was purified 680-fold with a 31% yield. The sialyltransferase is originally associated with the high molecular weight particle also carrying the aggregation factor. In the last step the aggregation factor was separated from the sialyltransferase. The enzyme catalyzes the transfer of sialic acid from CMP-sialic acid to the desialylated aggregation receptor. The molecular weight of the sialyltransferase has been determined to be 52,000. Kinetic studies revealed no lag phase and a dependence on enzyme concentration. The purified transferase has a pH optimum of 7.75 and requires 200 mM NaCl for activity. No requirement for Mg2+ or Ca2+ could be observed. The reaction is inhibited by 10 micronM N-ethylmaleimide."}
{"id": "PMID:16921", "title": "Compartmentalization of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in heart tissue.", "content": "In rabbit heart homogenates about 50% of the cAMP-dependent protein kinase activity was associated with the low speed particulate fraction. In homogenates of rat or beef heart this fraction represented approximately 30% of the activity. The percentage of the enzyme in the particulate fraction was not appreciably affected either by preparing more dilute homogenates or by aging homogenates for up to 2 h before centrifugation. The particulate enzyme was not solubilized at physiological ionic strength or by the presence of exogenous proteins during homogenization. However, the holoenzyme or regulatory subunit could be solubilized either by Triton X-100, high pH, or trypsin treatment. In hearts of all species studied, the particulate-bound protein kinase was mainly or entirely the type II isozyme, suggesting isozyme compartmentalization. In rabbit hearts perfused in the absence of hormones and homogenized in the presence of 0.25 M NaCl, at least 50% of the cAMP in homogenates was associated with the particulate fraction. Omitting NaCl reduced the amount of particulate-bound cAMP. Most of the particulate-bound cAMP was probably associated with the regulatory subunit in this fraction since approximately 70% of the bound nucleotide was solubilized by addition of homogeneous catalytic subunit to the particulate fraction. The amount of cAMP in the particulate fraction (0.16 nmol/g of tissue) was approximately one-half the amount of the regulatory subunit monomer (0.31 nmol/g of tissue) in this fraction. The calculated amount of catalytic subunit in the particulate fraction was 0.18 nmol/g of tissue. Either epinephrine alone or epinephrine plus 1-methyl-3-isobutylxanthine increased the cAMP content of the particulate and supernatant fractions. The cAMP level was increased more in the supernatant fraction, possibly because the cAMP level became saturating for the regulatory subunit in the particulate fraction. The increase in cAMP was associated with translocation of a large percentage of the catalytic subunit activity from the particulate to the supernatant fraction. The distribution of the regulatory subunit of the enzyme was not significantly affected by this treatment. The catalytic subunit translocation could be mimicked by addition of cAMP to homogenates before centrifugation. The data suggest that the regulatory subunit of the protein kinase, at least that of isozyme II, is bound to particulate material, and theactive catalytic subunit is released by formation of the regulatory subunit-cAMP complex when the tissue cAMP concentration is elevated. A model for compartmentalized hormonal control is presented.", "contents": "Compartmentalization of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in heart tissue. In rabbit heart homogenates about 50% of the cAMP-dependent protein kinase activity was associated with the low speed particulate fraction. In homogenates of rat or beef heart this fraction represented approximately 30% of the activity. The percentage of the enzyme in the particulate fraction was not appreciably affected either by preparing more dilute homogenates or by aging homogenates for up to 2 h before centrifugation. The particulate enzyme was not solubilized at physiological ionic strength or by the presence of exogenous proteins during homogenization. However, the holoenzyme or regulatory subunit could be solubilized either by Triton X-100, high pH, or trypsin treatment. In hearts of all species studied, the particulate-bound protein kinase was mainly or entirely the type II isozyme, suggesting isozyme compartmentalization. In rabbit hearts perfused in the absence of hormones and homogenized in the presence of 0.25 M NaCl, at least 50% of the cAMP in homogenates was associated with the particulate fraction. Omitting NaCl reduced the amount of particulate-bound cAMP. Most of the particulate-bound cAMP was probably associated with the regulatory subunit in this fraction since approximately 70% of the bound nucleotide was solubilized by addition of homogeneous catalytic subunit to the particulate fraction. The amount of cAMP in the particulate fraction (0.16 nmol/g of tissue) was approximately one-half the amount of the regulatory subunit monomer (0.31 nmol/g of tissue) in this fraction. The calculated amount of catalytic subunit in the particulate fraction was 0.18 nmol/g of tissue. Either epinephrine alone or epinephrine plus 1-methyl-3-isobutylxanthine increased the cAMP content of the particulate and supernatant fractions. The cAMP level was increased more in the supernatant fraction, possibly because the cAMP level became saturating for the regulatory subunit in the particulate fraction. The increase in cAMP was associated with translocation of a large percentage of the catalytic subunit activity from the particulate to the supernatant fraction. The distribution of the regulatory subunit of the enzyme was not significantly affected by this treatment. The catalytic subunit translocation could be mimicked by addition of cAMP to homogenates before centrifugation. The data suggest that the regulatory subunit of the protein kinase, at least that of isozyme II, is bound to particulate material, and theactive catalytic subunit is released by formation of the regulatory subunit-cAMP complex when the tissue cAMP concentration is elevated. A model for compartmentalized hormonal control is presented."}
{"id": "PMID:16922", "title": "Interaction of glucocorticoid hormones and cyclic nucleotides in induction of tyrosine aminotransferase in cultured hepatoma cells.", "content": "Reproducible induction of the enzyme tyrosine aminotransferase by dibutyryl cAMP (Bt2cAMP) in a line of HTC hepatoma cells in suspension culture requires that the cells be preinduced with dexamethasone, a synthetic glucocorticoid which itself induces tyrosine aminotransferase. Concentrations of dexamethasone that do not induce tyrosine aminotransferase fail to support Bt2cAMP induction, removal of the steroid from the medium leads to a loss of the Bt2cAMP effect, and an HTC cell line whose aminotransferase is not steroid-inducible does not respond to the cyclic nucleotide. We show that the further induction of tyrosine aminotransferase by Bt2cAMP in dexamethasone-treated cells is due to an increased rate of enzyme synthesis. The cyclic nucleotide has no effect on aminotransferase synthesis in cells grown in the absence of steroid. Several lines of evidence suggest that dexamethasone acts at a step beyond the activation of protein kinase by cAMP: (a) basal levels of cAMP are not altered by growth of HTC cells in dexamethasone; (b) accumulation of cAMP from the medium is not enhanced; (c) the glucocorticoid does not induce cAMP-dependent protein kinase in HTC cells; and (d) there is no augmentation of cAMP binding to the regulatory protein, nor is there any change in cAMP activation of protein kinase caused by growth in dexamethasone. These results help define a system that should be useful in studying the interaction of cyclic nucleotides and steroid hormones.", "contents": "Interaction of glucocorticoid hormones and cyclic nucleotides in induction of tyrosine aminotransferase in cultured hepatoma cells. Reproducible induction of the enzyme tyrosine aminotransferase by dibutyryl cAMP (Bt2cAMP) in a line of HTC hepatoma cells in suspension culture requires that the cells be preinduced with dexamethasone, a synthetic glucocorticoid which itself induces tyrosine aminotransferase. Concentrations of dexamethasone that do not induce tyrosine aminotransferase fail to support Bt2cAMP induction, removal of the steroid from the medium leads to a loss of the Bt2cAMP effect, and an HTC cell line whose aminotransferase is not steroid-inducible does not respond to the cyclic nucleotide. We show that the further induction of tyrosine aminotransferase by Bt2cAMP in dexamethasone-treated cells is due to an increased rate of enzyme synthesis. The cyclic nucleotide has no effect on aminotransferase synthesis in cells grown in the absence of steroid. Several lines of evidence suggest that dexamethasone acts at a step beyond the activation of protein kinase by cAMP: (a) basal levels of cAMP are not altered by growth of HTC cells in dexamethasone; (b) accumulation of cAMP from the medium is not enhanced; (c) the glucocorticoid does not induce cAMP-dependent protein kinase in HTC cells; and (d) there is no augmentation of cAMP binding to the regulatory protein, nor is there any change in cAMP activation of protein kinase caused by growth in dexamethasone. These results help define a system that should be useful in studying the interaction of cyclic nucleotides and steroid hormones."}
{"id": "PMID:16924", "title": "Effect of hydrostatic pressure on ligand binding to hemoglobin.", "content": "Increase in hydrostatic pressure to 1000 atm increased the affinity of human and menhaden (Brevoortia tyrannus) hemoglobins for oxygen. With necessary assumptions about the form of the equilibrium curve, and after correction for changes in pH and volume due to pressure, the increase in affinity is about 2-fold for both hemoglobins. At pH 6.5, Hill's n for menhaden hemoglobin is near 1, and it is believed to remain in the T state, whereas human hemoglobin undergoes a T to R transition. This suggests that the R-T equilibrium is not disturbed by pressure. In direct experiments the binding of a fluorescent effector (8 hydroxy-1,3,6-pyrene (trisulfonic acid) to deoxyhemoglobin was not changed by pressure. The binding of n-butylisocyanide to hemoglobin and to myoglobin is also greater at high pressures, similarly suggesting that the R-T transition is not involved in the pressure effect.", "contents": "Effect of hydrostatic pressure on ligand binding to hemoglobin. Increase in hydrostatic pressure to 1000 atm increased the affinity of human and menhaden (Brevoortia tyrannus) hemoglobins for oxygen. With necessary assumptions about the form of the equilibrium curve, and after correction for changes in pH and volume due to pressure, the increase in affinity is about 2-fold for both hemoglobins. At pH 6.5, Hill's n for menhaden hemoglobin is near 1, and it is believed to remain in the T state, whereas human hemoglobin undergoes a T to R transition. This suggests that the R-T equilibrium is not disturbed by pressure. In direct experiments the binding of a fluorescent effector (8 hydroxy-1,3,6-pyrene (trisulfonic acid) to deoxyhemoglobin was not changed by pressure. The binding of n-butylisocyanide to hemoglobin and to myoglobin is also greater at high pressures, similarly suggesting that the R-T transition is not involved in the pressure effect."}
{"id": "PMID:16925", "title": "Charges of nicotinamide adenine nucleotides and adenylate energy charge as regulatory parameters of the metabolism in Escherichia coli.", "content": "Methods for measurements of catabolic reduction charge (defined as NADH/(NADH+NAD+)) and anabolic reduction charge (defined as NADPH/(NADPH + NADP+)) are described using [14C]nicotinamide labeling of Escherichia coli cultures. Together with these parameters the adenylate energy charge (ATP + 1/2ADP)/(ATP + ADP + AMP) was measured using labeling with [2-3H]adenine. These three charges were found under different exponential growth conditions to have values independent of the growth conditions: catabolic reduction charge, 0.05; anabolic reduction charge, 0.45; and adenylate energy charge, 0.9. The charges were examined during interruption of growth primarily affecting catabolism, respiration, or anabolism, leading to changes of the charges. The changes of charges are evaluated as a possible regulation of the metabolic rates utilizing or producing the nucleotides by their respective charges.", "contents": "Charges of nicotinamide adenine nucleotides and adenylate energy charge as regulatory parameters of the metabolism in Escherichia coli. Methods for measurements of catabolic reduction charge (defined as NADH/(NADH+NAD+)) and anabolic reduction charge (defined as NADPH/(NADPH + NADP+)) are described using [14C]nicotinamide labeling of Escherichia coli cultures. Together with these parameters the adenylate energy charge (ATP + 1/2ADP)/(ATP + ADP + AMP) was measured using labeling with [2-3H]adenine. These three charges were found under different exponential growth conditions to have values independent of the growth conditions: catabolic reduction charge, 0.05; anabolic reduction charge, 0.45; and adenylate energy charge, 0.9. The charges were examined during interruption of growth primarily affecting catabolism, respiration, or anabolism, leading to changes of the charges. The changes of charges are evaluated as a possible regulation of the metabolic rates utilizing or producing the nucleotides by their respective charges."}
{"id": "PMID:16933", "title": "Phosphoprotein phosphatase activity associated with the cytoplasmic membrane of Salmonella typhimurium and Escherichia coli.", "content": "Membrane-associated phosphoprotein phosphatase activity was demonstrated in extracts of Salmonella typhimurium and Escherichia coli. The active protein could be extracted from the membrane as a large water-soluble complex (Mr greater than 150,000). Maximal activity was observed at pH 6 to 7 in the presence of a divalent cation. The enzyme appears to be distinct from previously described phosphatases.", "contents": "Phosphoprotein phosphatase activity associated with the cytoplasmic membrane of Salmonella typhimurium and Escherichia coli. Membrane-associated phosphoprotein phosphatase activity was demonstrated in extracts of Salmonella typhimurium and Escherichia coli. The active protein could be extracted from the membrane as a large water-soluble complex (Mr greater than 150,000). Maximal activity was observed at pH 6 to 7 in the presence of a divalent cation. The enzyme appears to be distinct from previously described phosphatases."}
{"id": "PMID:16935", "title": "In vitro activation of the in vivo colony-forming units of the mouse yolk sac.", "content": "Experiments were performed to investigate the presence of colony-forming units (CFU) in the mouse embryonic yolk sac during the developmental period in which the yolk sac is the sole hemopoietic organ. Injection of yolk sac cell suspensions from normal embryos into syngeneic, lethally irradiated adult recipients evoked a very low number of spleen colonies. However, prior cultivation of yolk sacs in vitro caused a dramatic increase in the spleen colony-forming capacity--as high as 84-fold--following 48 hours in culture. The yolk sac origin of the spleen colonies was confirmed by: (a) Chromosomal marker analysis; (b) dose-response analysis; (c) demonstrating that the above colonies were not of endogenous origin induced by the mere injection of grafted cells. We conclude that the yolk sac contains many precursors of colony-forming cells which though undetectable by immediate grafting apparently become activated in culture by an as yet unknown induction process.", "contents": "In vitro activation of the in vivo colony-forming units of the mouse yolk sac. Experiments were performed to investigate the presence of colony-forming units (CFU) in the mouse embryonic yolk sac during the developmental period in which the yolk sac is the sole hemopoietic organ. Injection of yolk sac cell suspensions from normal embryos into syngeneic, lethally irradiated adult recipients evoked a very low number of spleen colonies. However, prior cultivation of yolk sacs in vitro caused a dramatic increase in the spleen colony-forming capacity--as high as 84-fold--following 48 hours in culture. The yolk sac origin of the spleen colonies was confirmed by: (a) Chromosomal marker analysis; (b) dose-response analysis; (c) demonstrating that the above colonies were not of endogenous origin induced by the mere injection of grafted cells. We conclude that the yolk sac contains many precursors of colony-forming cells which though undetectable by immediate grafting apparently become activated in culture by an as yet unknown induction process."}
{"id": "PMID:16936", "title": "The diverse effects of 5'-bromodeoxyuridine on enzyme activities in cultured H35 hepatoma cells.", "content": "Reuber (H35) hepatoma cells were grown in medium containing 10(-5)M bromodeoxyuridine (BrdU), which was incorporated into their DNA. Cell growth rate was unaffected by BrdU for the first two generations, after which it was reduced by about 50%. The effect of BrdU incorporation on the activities of several enzymes with rapid turnover rates was examined to test the hypothesis that the synthesis of such enzymes will be preferentially inhibited by BrdU. Tyrosine amino-transferase (TAT) activity decreased by 70% within two generations whereas thymidine kinase activity remained at control values. PEP carboxykinase activity was unchanged during the first generation in BrdU-containing medium but, during the second, its activity increased by at least 30%. Ornithine decarboxylase levels decreased by about 50% only after two generations in the presence of BrdU. There appeared to be no simple relationship between turnover rates and the effect of BrdU on enzyme activity. Incorporation of BrdU was found to inhibit the induction of both TAT and PEP carboxykinase by dexamethasone and to enhance the inhibition of cell growth by this steroid. These results are discussed with respect to possible mechanisms of gene expression and development in both normal and neoplastic cells.", "contents": "The diverse effects of 5'-bromodeoxyuridine on enzyme activities in cultured H35 hepatoma cells. Reuber (H35) hepatoma cells were grown in medium containing 10(-5)M bromodeoxyuridine (BrdU), which was incorporated into their DNA. Cell growth rate was unaffected by BrdU for the first two generations, after which it was reduced by about 50%. The effect of BrdU incorporation on the activities of several enzymes with rapid turnover rates was examined to test the hypothesis that the synthesis of such enzymes will be preferentially inhibited by BrdU. Tyrosine amino-transferase (TAT) activity decreased by 70% within two generations whereas thymidine kinase activity remained at control values. PEP carboxykinase activity was unchanged during the first generation in BrdU-containing medium but, during the second, its activity increased by at least 30%. Ornithine decarboxylase levels decreased by about 50% only after two generations in the presence of BrdU. There appeared to be no simple relationship between turnover rates and the effect of BrdU on enzyme activity. Incorporation of BrdU was found to inhibit the induction of both TAT and PEP carboxykinase by dexamethasone and to enhance the inhibition of cell growth by this steroid. These results are discussed with respect to possible mechanisms of gene expression and development in both normal and neoplastic cells."}
{"id": "PMID:16937", "title": "The relation of cycling of intracellular pH to mitosis in the acellular slime mould Physarum polycephalum.", "content": "The relation between intracellular pH and the mitotic cycle of Physarum polycephalum was studied by two-independent techniques. Both techniques revealed a long term cycling of intracellular pH which has the same period as the mitotic cycle, Qualitative detection of the changes in intracellular pH was made by measuring the changes in fluorescence of 4-methylesculetin which had been absorbed by the plasmodium. Quantitative measurements of intracellular pH were made throughout the mitotic cycle with antimony micro pH electrodes. The cycle of intracellular pH is sinusoidal in appearance. The maximum intracellular pH (pH 6.6) occurred at, or very near to, mitosis, and was approximately 0.6 pH units higher than the minimum pH, which occurred near the middle of the mitotic cycle.", "contents": "The relation of cycling of intracellular pH to mitosis in the acellular slime mould Physarum polycephalum. The relation between intracellular pH and the mitotic cycle of Physarum polycephalum was studied by two-independent techniques. Both techniques revealed a long term cycling of intracellular pH which has the same period as the mitotic cycle, Qualitative detection of the changes in intracellular pH was made by measuring the changes in fluorescence of 4-methylesculetin which had been absorbed by the plasmodium. Quantitative measurements of intracellular pH were made throughout the mitotic cycle with antimony micro pH electrodes. The cycle of intracellular pH is sinusoidal in appearance. The maximum intracellular pH (pH 6.6) occurred at, or very near to, mitosis, and was approximately 0.6 pH units higher than the minimum pH, which occurred near the middle of the mitotic cycle."}
{"id": "PMID:16938", "title": "Evaluation of the Hall electrolytic conductivity detector for the analysis of narcotic alkaloid and phenothiazine drugs extracted from urine.", "content": "The electrolytic conductivity detector can be used for the rapid and selective determination of narcotic alkaloid and phenothiazine drugs in the presence of urine coextractants. The high selectivity of the detector enables drug concentrations as low as 0.1 mg/dl to be analyzed without extensive sample cleanup or derivatization.", "contents": "Evaluation of the Hall electrolytic conductivity detector for the analysis of narcotic alkaloid and phenothiazine drugs extracted from urine. The electrolytic conductivity detector can be used for the rapid and selective determination of narcotic alkaloid and phenothiazine drugs in the presence of urine coextractants. The high selectivity of the detector enables drug concentrations as low as 0.1 mg/dl to be analyzed without extensive sample cleanup or derivatization."}
{"id": "PMID:16939", "title": "Studies on the pathogenesis of an immune defect in multiple myeloma.", "content": "The reduced capacity of patients with multiple myeloma to respond to antigen challenge is well recognized. Response to antigen involves antigen recognition, cell proliferation, and synthesis and secretion of antibody. This study examines this sequence of events in peripheral blood lymphocytes from untreated and treated patients with myeloma, from individuals with benign monoclonal gammopathy, and from normal healthy donors. Antigen-binding capacity was assessed by testing the ability of lymphocytes to bind radio-labeled pneumococcal polysaccharide, tetanus toxoid, or diptheria toxin. The in vitro proliferative response to these antigens as well as to pokeweed mitogen and streptokinase-streptodornase was evaluated. The secretion of immunoglobulin in response to pneumococcal polysaccharide, tetanus toxoid, and pokeweed mitogen by 2-4 x 10(6) lymphocytes in 7-day cultures was determined. The effects of coculture of myeloma peripheral blood lymphocytes and normal peripheral blood lymphocytes on immunoglobulin production and mixed leukocyte reactions were explored. All myeloma patients had normal numbers (3-8/5,000 cells) of antigen-binding cells. However, most showed a diminished antigen-induced blast transformation as measured by uptake of [(125)I]5-iodo-2'-deoxyuridine in culture. Immunoglobulin production in response to specific antigen in myeloma lymphocytes was 30-80% less than in normal lymphocytes. Immunoglobulin synthesis and mixed leukocyte responses by normal peripheral blood lymphocytes could be suppressed by myeloma lymphocytes. Multiple suppressor populations were present. Thus, the immune defect in myeloma is beyond the antigen recognition step and involves both the proliferation of antigen-sensitive cells and immunoglobulin production. Further suppressive effects are imposed on normal cells, implying defects in immunoregulation in this disease.", "contents": "Studies on the pathogenesis of an immune defect in multiple myeloma. The reduced capacity of patients with multiple myeloma to respond to antigen challenge is well recognized. Response to antigen involves antigen recognition, cell proliferation, and synthesis and secretion of antibody. This study examines this sequence of events in peripheral blood lymphocytes from untreated and treated patients with myeloma, from individuals with benign monoclonal gammopathy, and from normal healthy donors. Antigen-binding capacity was assessed by testing the ability of lymphocytes to bind radio-labeled pneumococcal polysaccharide, tetanus toxoid, or diptheria toxin. The in vitro proliferative response to these antigens as well as to pokeweed mitogen and streptokinase-streptodornase was evaluated. The secretion of immunoglobulin in response to pneumococcal polysaccharide, tetanus toxoid, and pokeweed mitogen by 2-4 x 10(6) lymphocytes in 7-day cultures was determined. The effects of coculture of myeloma peripheral blood lymphocytes and normal peripheral blood lymphocytes on immunoglobulin production and mixed leukocyte reactions were explored. All myeloma patients had normal numbers (3-8/5,000 cells) of antigen-binding cells. However, most showed a diminished antigen-induced blast transformation as measured by uptake of [(125)I]5-iodo-2'-deoxyuridine in culture. Immunoglobulin production in response to specific antigen in myeloma lymphocytes was 30-80% less than in normal lymphocytes. Immunoglobulin synthesis and mixed leukocyte responses by normal peripheral blood lymphocytes could be suppressed by myeloma lymphocytes. Multiple suppressor populations were present. Thus, the immune defect in myeloma is beyond the antigen recognition step and involves both the proliferation of antigen-sensitive cells and immunoglobulin production. Further suppressive effects are imposed on normal cells, implying defects in immunoregulation in this disease."}
{"id": "PMID:16940", "title": "Aminoglycoside antibiotics and renal function: changes in urinary gamma-glutamyltransferase excretion.", "content": "The urinary excretion of the renal proximal tubular enzyme, gamma-glutamyltransferase (gamma-GT), has been studied in 41 patients receiving tobramycin, gentamicin or streptomycin for a variety of infections. All patients receiving tobramycin or gentamicin have shown increased excretion of gamma-GT in the urine. Only 46% of those receiving streptomycin have shown an increase in gamma-GT excretion and this is of a lesser degree. A change in creatinine clearance which could only be explained by antibiotic administration was detected in three patients (2 on gentamicin, 1 on streptomycin). The degree of elevation of urinary gamma-GT activity was greater when the initial creatinine clearance was lower, and it is therefore suggested that those patients with pre-existing renal dysfunction should be monitored particularly carefully for signs of nephrotoxicity from these antibiotics. Urinary gamma-GT is a useful enzyme in the investigation of renal drug effects.", "contents": "Aminoglycoside antibiotics and renal function: changes in urinary gamma-glutamyltransferase excretion. The urinary excretion of the renal proximal tubular enzyme, gamma-glutamyltransferase (gamma-GT), has been studied in 41 patients receiving tobramycin, gentamicin or streptomycin for a variety of infections. All patients receiving tobramycin or gentamicin have shown increased excretion of gamma-GT in the urine. Only 46% of those receiving streptomycin have shown an increase in gamma-GT excretion and this is of a lesser degree. A change in creatinine clearance which could only be explained by antibiotic administration was detected in three patients (2 on gentamicin, 1 on streptomycin). The degree of elevation of urinary gamma-GT activity was greater when the initial creatinine clearance was lower, and it is therefore suggested that those patients with pre-existing renal dysfunction should be monitored particularly carefully for signs of nephrotoxicity from these antibiotics. Urinary gamma-GT is a useful enzyme in the investigation of renal drug effects."}
{"id": "PMID:16943", "title": "Effect of beta adrenergic agonist, prostaglandins, and cortisol on lymphocyte levels of cyclic adenosine monophosphate and glycogen: abnormal lymphocytic metabolism in asthma.", "content": "Decreased beta adrenergic regulation of cyclic adenosine monophosphate (cAMP) in lymphocytes has been described in asthma. We investigated adrenergic stimulation of glycogenolysis and responses to prostaglandin E1 (PGE1). Lymphocytes from 24 normal and 24 mild asthmatic subjects who had no drugs for at least 2 weeks were separated on Ficoll-hypaque and incubated in medium 199 with Hepes buffer. Beta adrenergic stimulation of cAMP and glycogenolysis was reduced in the asthmatics (p less than 0.05). PGE produced less of a rise in cAMP in asthmatics than in normals, but the difference was not significant (p greater than 0.05) and glycogenolysis was normal. Cortisol added in vitro potentiates the effect of isoproterenol and PGE1--but in the presence of cortisol the response of the asthmatic cells to isoproterenol is still lower than that of normal cells. This observation would support that \"beta adrenergic blockade\" is the major defect of asthmatic cells. The conclusion is further supported by the observation that the degree of the blockade is associated with a pathologic condition.", "contents": "Effect of beta adrenergic agonist, prostaglandins, and cortisol on lymphocyte levels of cyclic adenosine monophosphate and glycogen: abnormal lymphocytic metabolism in asthma. Decreased beta adrenergic regulation of cyclic adenosine monophosphate (cAMP) in lymphocytes has been described in asthma. We investigated adrenergic stimulation of glycogenolysis and responses to prostaglandin E1 (PGE1). Lymphocytes from 24 normal and 24 mild asthmatic subjects who had no drugs for at least 2 weeks were separated on Ficoll-hypaque and incubated in medium 199 with Hepes buffer. Beta adrenergic stimulation of cAMP and glycogenolysis was reduced in the asthmatics (p less than 0.05). PGE produced less of a rise in cAMP in asthmatics than in normals, but the difference was not significant (p greater than 0.05) and glycogenolysis was normal. Cortisol added in vitro potentiates the effect of isoproterenol and PGE1--but in the presence of cortisol the response of the asthmatic cells to isoproterenol is still lower than that of normal cells. This observation would support that \"beta adrenergic blockade\" is the major defect of asthmatic cells. The conclusion is further supported by the observation that the degree of the blockade is associated with a pathologic condition."}
{"id": "PMID:16944", "title": "Further studies on the mechanism of human histamine-induced asthma: the effect of an aerosolized H1 receptor antagonist (diphenhydramine).", "content": "This study was designed to better define the mechanism of histamine-induced bronchoconstriction in humans by pharmacologic manipulation of the postulated bronchial histamine receptor sites. Histamine challenges were performed on a heterogeneous group of adult asthmatic subjects. The cumulative units of histamine required for induction of a sustained 20% or greater decrease in FEV1 from baseline were determined. The effect of pretreatment with an aerosolized H1 receptor antagonist, diphenhydramine hydrochloride, was then studied. Analysis of the data showed that the administration of an H1 receptor antagonist prior to histamine challenge significantly blocked the bronchial response to histamine (p less than 0.005). This effect was considered to be due to specific competitive antagonism at the H1 receptor site and suggests the presence of H1 receptors in human bronchial mucosa.", "contents": "Further studies on the mechanism of human histamine-induced asthma: the effect of an aerosolized H1 receptor antagonist (diphenhydramine). This study was designed to better define the mechanism of histamine-induced bronchoconstriction in humans by pharmacologic manipulation of the postulated bronchial histamine receptor sites. Histamine challenges were performed on a heterogeneous group of adult asthmatic subjects. The cumulative units of histamine required for induction of a sustained 20% or greater decrease in FEV1 from baseline were determined. The effect of pretreatment with an aerosolized H1 receptor antagonist, diphenhydramine hydrochloride, was then studied. Analysis of the data showed that the administration of an H1 receptor antagonist prior to histamine challenge significantly blocked the bronchial response to histamine (p less than 0.005). This effect was considered to be due to specific competitive antagonism at the H1 receptor site and suggests the presence of H1 receptors in human bronchial mucosa."}
{"id": "PMID:16945", "title": "[Acid-base equilibrium during acute fetal hypoxia. Experimental study].", "content": "The authors studied the effects of acute hypoxia of short duration in eight pregnant ewes that had been anaesthetised. They showed that during the experiment the E.E.G. as well as the pH and pCO and the maternal lactate levels were not changed and that therefore changes that can be found in the fetus are due solely to its own hypoxia and not due to transmission from the mother. In the fetus the trace flattens in about 30 minutes on an average. After this interval a moderate drop in pH occurs at the same time as an increase in lactacidemia and the relationship between lactate and pyruvate. The heart rate is changed in a variable manner: it accelerates if the basal rate is less than 180 beats a minute and slows if it is above 180. Blood pressure rises. Changes in the cardio-vascular system always precede those in the electroencephalograms.", "contents": "[Acid-base equilibrium during acute fetal hypoxia. Experimental study]. The authors studied the effects of acute hypoxia of short duration in eight pregnant ewes that had been anaesthetised. They showed that during the experiment the E.E.G. as well as the pH and pCO and the maternal lactate levels were not changed and that therefore changes that can be found in the fetus are due solely to its own hypoxia and not due to transmission from the mother. In the fetus the trace flattens in about 30 minutes on an average. After this interval a moderate drop in pH occurs at the same time as an increase in lactacidemia and the relationship between lactate and pyruvate. The heart rate is changed in a variable manner: it accelerates if the basal rate is less than 180 beats a minute and slows if it is above 180. Blood pressure rises. Changes in the cardio-vascular system always precede those in the electroencephalograms."}
{"id": "PMID:16972", "title": "Enhancement of murine cytomegalovirus infection during graft-vs.-host reaction.", "content": "A mouse model was used for elucidation of the role of a graft-vs-host reaction in promoting cytomegalovirus infection. F1 (DBA/2 X C3H/He) hybrid mice were infected with murine cytomegalovirus. Five weeks later, a graft-vs.-host reaction was produced in the chronically infected animals by the administration of multiple doses of DBA/2 parental splenocytes. Cytomegalovirus was recovered more often from the organs of mice undergoing graft-vs.-host reaction than from those of control animals (P less than 0.001). These results indicate that the graft-vs.-host reaction alone can enhance murine cytomegalovirus infection in a chronically infected host and may help explain the high incidence of cytomegalovirus infection after bone marrow allograft transplantation in man.", "contents": "Enhancement of murine cytomegalovirus infection during graft-vs.-host reaction. A mouse model was used for elucidation of the role of a graft-vs-host reaction in promoting cytomegalovirus infection. F1 (DBA/2 X C3H/He) hybrid mice were infected with murine cytomegalovirus. Five weeks later, a graft-vs.-host reaction was produced in the chronically infected animals by the administration of multiple doses of DBA/2 parental splenocytes. Cytomegalovirus was recovered more often from the organs of mice undergoing graft-vs.-host reaction than from those of control animals (P less than 0.001). These results indicate that the graft-vs.-host reaction alone can enhance murine cytomegalovirus infection in a chronically infected host and may help explain the high incidence of cytomegalovirus infection after bone marrow allograft transplantation in man."}
{"id": "PMID:16976", "title": "Protein binding to monosodium urate monohydrate, calcium pyrophosphate dihydrate, and silicon dioxide crystals. I. Physical characteristics.", "content": "The protein adsorptive properties of monosodium urate monohydrate (MSU), silica (Si), and calcium pyrophosphate dihydrate crystals were studied by qualitative and quantitative techniques. Immunoglobulin G (IgG) was adsorbed preferentially by MSU crystals from normal human serum and demonstrated high-affinity binding isotherms when compared with several isolated proteins in solution. The physical characteristics of this reaction suggest principally an ionic mechanism, since adsorption was enhanced by decreasing pH or ionic strength. Weaker physical forces also were suggested by studies showing enhanced adsorption at lower temperatures. The following order of affinity for Si or MSU crystals was found when equal concentrations of proteins were compared: Cohn fraction II greater than lysozyme greater than beta lactoglobulin greater than bovine serum albumin greater than ovalbumin. IgG adsorption to the crystals studied may explain certain features of their biological activity. It is suggested that this phenomenon blocks the membranolytic properties of crystals and stimulates their phagocytosis through interaction with Fc receptors on the surface of the phagocytic cells.", "contents": "Protein binding to monosodium urate monohydrate, calcium pyrophosphate dihydrate, and silicon dioxide crystals. I. Physical characteristics. The protein adsorptive properties of monosodium urate monohydrate (MSU), silica (Si), and calcium pyrophosphate dihydrate crystals were studied by qualitative and quantitative techniques. Immunoglobulin G (IgG) was adsorbed preferentially by MSU crystals from normal human serum and demonstrated high-affinity binding isotherms when compared with several isolated proteins in solution. The physical characteristics of this reaction suggest principally an ionic mechanism, since adsorption was enhanced by decreasing pH or ionic strength. Weaker physical forces also were suggested by studies showing enhanced adsorption at lower temperatures. The following order of affinity for Si or MSU crystals was found when equal concentrations of proteins were compared: Cohn fraction II greater than lysozyme greater than beta lactoglobulin greater than bovine serum albumin greater than ovalbumin. IgG adsorption to the crystals studied may explain certain features of their biological activity. It is suggested that this phenomenon blocks the membranolytic properties of crystals and stimulates their phagocytosis through interaction with Fc receptors on the surface of the phagocytic cells."}
{"id": "PMID:16977", "title": "Effect of CO2 concentration on phosphatidylcholine and phosphatidylglycerol metabolism in surfactant and residual lung fractions.", "content": "An investigation of the effect of change of total CO(2) concentration from 7 to 43 mM at pH 7.35 in the medium perfusing isolated rat lungs on [U-(14)C]glucose incorporation into lung phospholipids has been carried out. The incorporation of [U-(14)C]glucose into phosphatidylcholine and phosphatidylglycerol of the surfactant fraction and of the remaining lung tissue (residual fraction) was observed. Increased CO(2) concentration increased [U-(14)C]glucose incorporation into phosphatidylcholine of the surfactant fraction and residual fraction by 43 and 50%, respectively, during a 2 hr perfusion. Likewise, incorporation of [U-(14)C]glucose into phosphatidylglycerol was increased 22 and 34% into the surfactant and residual fractions, respectively. The percentage of [U-(14)C]glucose incorporated into the fatty acid moieties of phosphatidylcholine of both fractions increased as a result of increased CO(2) concentration. The increase in the incorporation of [U-(14)C]glucose into the fatty acid moieties of phosphatidylcholine was confirmed by an average increase of 56 and 77% in the specific activity of palmitic acid isolated from phosphatidylcholine of the surfactant and residual fraction, respectively, as a result of increased CO(2) concentration. The results suggest that alteration in extracellular CO(2) concentration affects the de novo synthesis from glucose of phosphatidylcholine and phosphatidylglycerol of the surfactant-lipoprotein fraction of lung.", "contents": "Effect of CO2 concentration on phosphatidylcholine and phosphatidylglycerol metabolism in surfactant and residual lung fractions. An investigation of the effect of change of total CO(2) concentration from 7 to 43 mM at pH 7.35 in the medium perfusing isolated rat lungs on [U-(14)C]glucose incorporation into lung phospholipids has been carried out. The incorporation of [U-(14)C]glucose into phosphatidylcholine and phosphatidylglycerol of the surfactant fraction and of the remaining lung tissue (residual fraction) was observed. Increased CO(2) concentration increased [U-(14)C]glucose incorporation into phosphatidylcholine of the surfactant fraction and residual fraction by 43 and 50%, respectively, during a 2 hr perfusion. Likewise, incorporation of [U-(14)C]glucose into phosphatidylglycerol was increased 22 and 34% into the surfactant and residual fractions, respectively. The percentage of [U-(14)C]glucose incorporated into the fatty acid moieties of phosphatidylcholine of both fractions increased as a result of increased CO(2) concentration. The increase in the incorporation of [U-(14)C]glucose into the fatty acid moieties of phosphatidylcholine was confirmed by an average increase of 56 and 77% in the specific activity of palmitic acid isolated from phosphatidylcholine of the surfactant and residual fraction, respectively, as a result of increased CO(2) concentration. The results suggest that alteration in extracellular CO(2) concentration affects the de novo synthesis from glucose of phosphatidylcholine and phosphatidylglycerol of the surfactant-lipoprotein fraction of lung."}
{"id": "PMID:16978", "title": "The significance of lipoprotein lipase in rat skeletal muscles.", "content": "Lipoprotein lipase was assayed in extracts of acetone-ether powders of rat skeletal muscles. Enzyme activity in soleus had typical characteristics of lipoprotein lipase in other tissues: inhibition by molar NaCl and protamine sulfate and activation by the human apolipoprotein, R-glutamic acid. Activity in muscles with predominantly red fibers (soleus, diaphragm, lateral head of gastrocnemius and anterior band of semitendinosus) was higher than in those with predominantly white fibers (body of gastrocnemius and posterior band of semitendinosus). No effect of a 24 hour fast upon enzyme activity was observed in ten skeletal muscles, but activity decreased substantially in four adipose tissue depots and increased slightly in heart muscle with fasting. Four minutes after intravenous injection of labeled lymph chylomicrons, skeletal muscles with predominantly red fibers incorporated several times more chylomicron triglyceride fatty acids than thos with predominantly white fibers. Estimated lipoprotein lipase activity in total skeletal muscle was about two-thirds that in total adipose tissue of rats fed ad libitum. After a 24 hour fast, total activity in skeletal muscle was about twice that in adipose tissue. These data suggest that a substantial fraction of lipoprotein lipase is in skeletal muscle of rats and that this tissue, especially its red fibers, is an important site of removal of triglycerides from the blood.", "contents": "The significance of lipoprotein lipase in rat skeletal muscles. Lipoprotein lipase was assayed in extracts of acetone-ether powders of rat skeletal muscles. Enzyme activity in soleus had typical characteristics of lipoprotein lipase in other tissues: inhibition by molar NaCl and protamine sulfate and activation by the human apolipoprotein, R-glutamic acid. Activity in muscles with predominantly red fibers (soleus, diaphragm, lateral head of gastrocnemius and anterior band of semitendinosus) was higher than in those with predominantly white fibers (body of gastrocnemius and posterior band of semitendinosus). No effect of a 24 hour fast upon enzyme activity was observed in ten skeletal muscles, but activity decreased substantially in four adipose tissue depots and increased slightly in heart muscle with fasting. Four minutes after intravenous injection of labeled lymph chylomicrons, skeletal muscles with predominantly red fibers incorporated several times more chylomicron triglyceride fatty acids than thos with predominantly white fibers. Estimated lipoprotein lipase activity in total skeletal muscle was about two-thirds that in total adipose tissue of rats fed ad libitum. After a 24 hour fast, total activity in skeletal muscle was about twice that in adipose tissue. These data suggest that a substantial fraction of lipoprotein lipase is in skeletal muscle of rats and that this tissue, especially its red fibers, is an important site of removal of triglycerides from the blood."}
{"id": "PMID:16979", "title": "Endocrine regulation of sex-dependent hydroxysteroid dehydrogenase activities in rat kidney: NADP-dependent microsomal 3alpha- and 20beta-hydroxysteroid dehydrogenase.", "content": "The NADP-dependent microsomal kidney enzymes, 3alpha- and 20beta-hydroxysteroid dehydrogenase (HSDH), which exhibit considerable sex differences in their activities (male:female activity ratios, 16:1 and 30:1 respectively), were investigated after interference with the pituitary-gonad and pituitary-adrenal systems. Prepubertal gonadectomy as well as hypophysectomy of mature male rats led to a decline in HSDH activity to almost that found in the normal female rat, whereas activities in female rats were unaffected. Testosterone induced typical male 3alpha-HSDH activity in both gonadectomized and hypophysectomized rats of either sex. Administration of 5alpha-dihydrotestosterone (5alpha-DHT) or 5alpha-androstane-3alpha, 17beta-diol to hypophysectomized male rats was equally effective in restoring full 3alpha- and 20beta-HSDH activities whereas 5alpha-androstane-3beta, 17beta-diol was less effective and dehydroepiandrosterone was ineffective. Simultaneous administration of cyproterone acetate did not block the inductive action of 5alpha-DHT. Administration of chorionic gonadotrophin, pregnant mare serum gonadotrophin or a combination of luteinizing hormone and follicle-stimulating hormone to hypophysectomized male rats all led to parallel increases in the weight of the seminal vesicles and in both renal enzyme activities; administration of growth hormone, prolactin or thyroid-stimulating hormone was ineffective. Adrenalectomy of gonadectomized, but not of hypophysectomized male rats, caused a further drop in activity to the normal female level. Adrenalectomy of otherwise intact rats did not affect either enzyme activity. The hypophysis was involved in the regulation of the two NADP-dependent renal HSDH activities through its gonadotrophic function in male rats; adrenal secretions were of little physiological significance.", "contents": "Endocrine regulation of sex-dependent hydroxysteroid dehydrogenase activities in rat kidney: NADP-dependent microsomal 3alpha- and 20beta-hydroxysteroid dehydrogenase. The NADP-dependent microsomal kidney enzymes, 3alpha- and 20beta-hydroxysteroid dehydrogenase (HSDH), which exhibit considerable sex differences in their activities (male:female activity ratios, 16:1 and 30:1 respectively), were investigated after interference with the pituitary-gonad and pituitary-adrenal systems. Prepubertal gonadectomy as well as hypophysectomy of mature male rats led to a decline in HSDH activity to almost that found in the normal female rat, whereas activities in female rats were unaffected. Testosterone induced typical male 3alpha-HSDH activity in both gonadectomized and hypophysectomized rats of either sex. Administration of 5alpha-dihydrotestosterone (5alpha-DHT) or 5alpha-androstane-3alpha, 17beta-diol to hypophysectomized male rats was equally effective in restoring full 3alpha- and 20beta-HSDH activities whereas 5alpha-androstane-3beta, 17beta-diol was less effective and dehydroepiandrosterone was ineffective. Simultaneous administration of cyproterone acetate did not block the inductive action of 5alpha-DHT. Administration of chorionic gonadotrophin, pregnant mare serum gonadotrophin or a combination of luteinizing hormone and follicle-stimulating hormone to hypophysectomized male rats all led to parallel increases in the weight of the seminal vesicles and in both renal enzyme activities; administration of growth hormone, prolactin or thyroid-stimulating hormone was ineffective. Adrenalectomy of gonadectomized, but not of hypophysectomized male rats, caused a further drop in activity to the normal female level. Adrenalectomy of otherwise intact rats did not affect either enzyme activity. The hypophysis was involved in the regulation of the two NADP-dependent renal HSDH activities through its gonadotrophic function in male rats; adrenal secretions were of little physiological significance."}
{"id": "PMID:16980", "title": "[A comparision of different methods and reagents for the determination of gamma-glutamyl transferase in serum (author's transl)].", "content": "Four commercially available kinetic photometric tests for the determination of gamma-glutamyl transferase were compared. Test A is based on the substrate L-gamma-glutamyl-4-nitroanilide; test B uses this same substrate dissolved in hydrochloric acid. C1 and C2 are tests from different suppliers; both use the substrate L-gamma-glutamyl-3-carboxy-4-nitroanilide, and all other constituents are the same as quoted by the suppliers. Parallel determinations were performed on 1017 native sera and 12 control sera. Compared with values from test A, two of the three other tests showed statistically significant differences in the diagnostically important range 10 to 50 U/l. Significant differences were also observed between the results from the apparently identical tests, C1, and C2. The values obtained for control sera showed a dependence on the test procedure and/or composition.", "contents": "[A comparision of different methods and reagents for the determination of gamma-glutamyl transferase in serum (author's transl)]. Four commercially available kinetic photometric tests for the determination of gamma-glutamyl transferase were compared. Test A is based on the substrate L-gamma-glutamyl-4-nitroanilide; test B uses this same substrate dissolved in hydrochloric acid. C1 and C2 are tests from different suppliers; both use the substrate L-gamma-glutamyl-3-carboxy-4-nitroanilide, and all other constituents are the same as quoted by the suppliers. Parallel determinations were performed on 1017 native sera and 12 control sera. Compared with values from test A, two of the three other tests showed statistically significant differences in the diagnostically important range 10 to 50 U/l. Significant differences were also observed between the results from the apparently identical tests, C1, and C2. The values obtained for control sera showed a dependence on the test procedure and/or composition."}
{"id": "PMID:16982", "title": "Exchange diffusion of dopamine induced in planar lipid bilayer membranes by the ionophore X537A.", "content": "The ionophore X537A causes a large increase in the [(14)C]dopamine (a catecholamine) permeability of planar bilayer membranes. Dopamine transport increases linearly with the ionophore concentration. At relatively high concentrations in the presence of dopamine, the ionophore omdices a conductance which is nearly ideally selective for the dopamine cation. However, the total dopamine flux as determined in tracer experiments is not affected by an electric field and is over 10(5) times larger than predicted from the estimated dopamine conductance. Increasing the dopamine concentration on the side containing radioactive dopamine (the cis side) saturates the dopamine transport. This saturation is relieved by trans addition of nonradioactive dopamine, tyramine, H(+), or K(+). With unequal concentrations of dopamine cis and trans (49 and 12.5 mM), the unidirectional dopamine fluxes are equal. Increasing H(+) cis and trans decreases dopamine transport. It is concluded that at physiological pH, the X537A-induced transport of dopamine occurs via an electrically silent exchange diffusion of dopamine cation with another cation (e.g., dopamine(+), H(+), or K(+)). X537A induces a Ca(++)-independent release of catecholamines from sympathetic nerves by interfering with intracellular storage within storage vesicles (R.W. Holz. 1975. Biochim. Biophys. Acta. 375:138-152). It is suggested that X537A causes an exchange of intravesicular catecholamine with a cytoplasmic cation (perhaps K(+) or H(+)) across the storage vesicle membrane.", "contents": "Exchange diffusion of dopamine induced in planar lipid bilayer membranes by the ionophore X537A. The ionophore X537A causes a large increase in the [(14)C]dopamine (a catecholamine) permeability of planar bilayer membranes. Dopamine transport increases linearly with the ionophore concentration. At relatively high concentrations in the presence of dopamine, the ionophore omdices a conductance which is nearly ideally selective for the dopamine cation. However, the total dopamine flux as determined in tracer experiments is not affected by an electric field and is over 10(5) times larger than predicted from the estimated dopamine conductance. Increasing the dopamine concentration on the side containing radioactive dopamine (the cis side) saturates the dopamine transport. This saturation is relieved by trans addition of nonradioactive dopamine, tyramine, H(+), or K(+). With unequal concentrations of dopamine cis and trans (49 and 12.5 mM), the unidirectional dopamine fluxes are equal. Increasing H(+) cis and trans decreases dopamine transport. It is concluded that at physiological pH, the X537A-induced transport of dopamine occurs via an electrically silent exchange diffusion of dopamine cation with another cation (e.g., dopamine(+), H(+), or K(+)). X537A induces a Ca(++)-independent release of catecholamines from sympathetic nerves by interfering with intracellular storage within storage vesicles (R.W. Holz. 1975. Biochim. Biophys. Acta. 375:138-152). It is suggested that X537A causes an exchange of intravesicular catecholamine with a cytoplasmic cation (perhaps K(+) or H(+)) across the storage vesicle membrane."}
{"id": "PMID:16983", "title": "The rumen flagellate Piromonas communis: its life-history and invasion of plant material in the rumen.", "content": "The rumen flagellat Piromonas communis is the zoospore of a phycomycete fungus inhabiting the rumen. Zoosporogenesis was stimulated by a dietary component (the inducer), and inhibited by compounds affecting membrane structure and function, but not by inhibitors of protein synthesis. The zoospores showed taxis towards the tissues surrounding the inflorescence of Lolium perenne L. in the rumen, invading principally the stomata and damaged tissues. The zoospores germinated on this substratum and the rhizoids of the developing vegetative stage penetrated the tissue, taking up C14 from labelled plant material, which was incorporated into the fungal cells. The conditions for maximum flagellate production (39 degrees C, pH 6-0 to 7-0, high concentration of CO2, absence of O2) resembled those found in the rumen. The organism was cultured in an undefined medium in vitro in the absence of other flagellates.", "contents": "The rumen flagellate Piromonas communis: its life-history and invasion of plant material in the rumen. The rumen flagellat Piromonas communis is the zoospore of a phycomycete fungus inhabiting the rumen. Zoosporogenesis was stimulated by a dietary component (the inducer), and inhibited by compounds affecting membrane structure and function, but not by inhibitors of protein synthesis. The zoospores showed taxis towards the tissues surrounding the inflorescence of Lolium perenne L. in the rumen, invading principally the stomata and damaged tissues. The zoospores germinated on this substratum and the rhizoids of the developing vegetative stage penetrated the tissue, taking up C14 from labelled plant material, which was incorporated into the fungal cells. The conditions for maximum flagellate production (39 degrees C, pH 6-0 to 7-0, high concentration of CO2, absence of O2) resembled those found in the rumen. The organism was cultured in an undefined medium in vitro in the absence of other flagellates."}
{"id": "PMID:16991", "title": "The effects of beta adrenergic blockade on spinal cord autoregulation in the monkey.", "content": "Blood flow in the spinal cord was measured in a group of monkeys over a wide range of artificially varied blood pressures after the administration of propranolol, a beta adrenergic blocker. Spinal cord blood flow was found to be constant and in the normal range between a mean system arterial blood pressure of 50 to 150 mm Hg. From 150 to 180 mm Hg spinal cord blood flow decreased. There was no breakthrough of autoregulation, previously seen in the untreated animal. It is suggested, therefore, that the previously observed breakthrough of autoregulation is a beta adrenergic-mediated phenomenon.", "contents": "The effects of beta adrenergic blockade on spinal cord autoregulation in the monkey. Blood flow in the spinal cord was measured in a group of monkeys over a wide range of artificially varied blood pressures after the administration of propranolol, a beta adrenergic blocker. Spinal cord blood flow was found to be constant and in the normal range between a mean system arterial blood pressure of 50 to 150 mm Hg. From 150 to 180 mm Hg spinal cord blood flow decreased. There was no breakthrough of autoregulation, previously seen in the untreated animal. It is suggested, therefore, that the previously observed breakthrough of autoregulation is a beta adrenergic-mediated phenomenon."}
{"id": "PMID:16993", "title": "In vivo effects of glucagon on fatty acid synthesis in fasted and refed rats.", "content": "Since altered nutritional states evoke compensatory changes in systemic levels of several hormones, the present study was conducted to determine in vivo effects of glucagon and insulin on hepatic and adipose tissue lipogenesis in fed, fasted (3-days) and refed (3-days) rats. Compared to the fed controls, glucagon reduced hepatic fatty acid synthesis and acetyl CoA carboxylase activity by 62% and 65% in fed rats, and by 51% and 48%, respectively, in refed rats. In contrast, glucagon had no effect on fatty acid synthesis or acetyl CoA carboxylase activity in adipose tissue of any of the three experimental groups. Exogenous insulin antagonized the glucagon effects and restored hepatic fatty acid synthesis and enzyme activity in fed or refed rats. No glucagon or insulin effects were observed in fasting rats. In addition, glucagon reduced in vivo incorporation of acetate into hepatic cholesterol by about 33% and into fatty acids of the liver, and heart and the kidney by 33%, 77% and 30%, respectively. The hormone had no effect on fatty acid synthesis in the muscle.", "contents": "In vivo effects of glucagon on fatty acid synthesis in fasted and refed rats. Since altered nutritional states evoke compensatory changes in systemic levels of several hormones, the present study was conducted to determine in vivo effects of glucagon and insulin on hepatic and adipose tissue lipogenesis in fed, fasted (3-days) and refed (3-days) rats. Compared to the fed controls, glucagon reduced hepatic fatty acid synthesis and acetyl CoA carboxylase activity by 62% and 65% in fed rats, and by 51% and 48%, respectively, in refed rats. In contrast, glucagon had no effect on fatty acid synthesis or acetyl CoA carboxylase activity in adipose tissue of any of the three experimental groups. Exogenous insulin antagonized the glucagon effects and restored hepatic fatty acid synthesis and enzyme activity in fed or refed rats. No glucagon or insulin effects were observed in fasting rats. In addition, glucagon reduced in vivo incorporation of acetate into hepatic cholesterol by about 33% and into fatty acids of the liver, and heart and the kidney by 33%, 77% and 30%, respectively. The hormone had no effect on fatty acid synthesis in the muscle."}
{"id": "PMID:16995", "title": "Effects of putative neurotransmitters on the motor activity of Spirometra mansonoides.", "content": "5-Hydroxytryptamine (5-HT), epinephrine, and dopamine strongly stimulated the motor activity of larval Spirometra mansonoides. By contrast, a cholinomimetic agent, arecoline, paralyzed the worms. There was some pharmacological specificity among the agonists but not with various antagonists. Acetylcholinesterase activity was present in both larval and adult Spirometra.", "contents": "Effects of putative neurotransmitters on the motor activity of Spirometra mansonoides. 5-Hydroxytryptamine (5-HT), epinephrine, and dopamine strongly stimulated the motor activity of larval Spirometra mansonoides. By contrast, a cholinomimetic agent, arecoline, paralyzed the worms. There was some pharmacological specificity among the agonists but not with various antagonists. Acetylcholinesterase activity was present in both larval and adult Spirometra."}
{"id": "PMID:16997", "title": "Actions of iontophoretic phenytoin and medazepam on hippocampal neurons.", "content": "In rats anesthetized with methoxyflurane, phenytoin (DPH) and medazepam (MDZ) were administered iontophoretically to pyramidal and granule cells discharging spontaneously or being driven by acetylcholine or glutamic acid. The objectives were to determine if: 1) these anticonvulsant agents exert direct effects on the rates of discharge of hippocampal neurons; 2) similarities exist between responses elicited by DPH and MDZ; and 3) pyramidal and granule cells differ in their responsiveness to the drugs. The firing rates of 38% of spontaneously active neurons were reduced by iontophoretic DPH. The incidence of depression by DPH depended upon the pretest discharge rates of the cells. Only 5% of cells with spontaneous rates less than 12/sec were depressed by DPH, but 80% with rates faster than 12/sec were inhibited. MDZ depressed 79% of spontaneously firing neurons regardless of pretest discharge rate. A majority of neurons whose firing rates were facilitated by either acetylcholine or glutamate were depressed by DPH or MDZ ejected iontophoretically. Pyramidal and granule cells responded similarly to putative transmitters, but differentially to the drugs. MDZ depressed a much greater proportion of spontaneously active granule cells then DPH. Phenytoin and MDZ differed with regard to the incidence of depression of spontaneous discharges, inhibition of slow firing cells, the proportion of granule cells depressed, and the duration of effect. These differences may be due to potency and pharmacokinetic factors or dissimilar mechanisms of action when the compounds are applied directly to single neurons.", "contents": "Actions of iontophoretic phenytoin and medazepam on hippocampal neurons. In rats anesthetized with methoxyflurane, phenytoin (DPH) and medazepam (MDZ) were administered iontophoretically to pyramidal and granule cells discharging spontaneously or being driven by acetylcholine or glutamic acid. The objectives were to determine if: 1) these anticonvulsant agents exert direct effects on the rates of discharge of hippocampal neurons; 2) similarities exist between responses elicited by DPH and MDZ; and 3) pyramidal and granule cells differ in their responsiveness to the drugs. The firing rates of 38% of spontaneously active neurons were reduced by iontophoretic DPH. The incidence of depression by DPH depended upon the pretest discharge rates of the cells. Only 5% of cells with spontaneous rates less than 12/sec were depressed by DPH, but 80% with rates faster than 12/sec were inhibited. MDZ depressed 79% of spontaneously firing neurons regardless of pretest discharge rate. A majority of neurons whose firing rates were facilitated by either acetylcholine or glutamate were depressed by DPH or MDZ ejected iontophoretically. Pyramidal and granule cells responded similarly to putative transmitters, but differentially to the drugs. MDZ depressed a much greater proportion of spontaneously active granule cells then DPH. Phenytoin and MDZ differed with regard to the incidence of depression of spontaneous discharges, inhibition of slow firing cells, the proportion of granule cells depressed, and the duration of effect. These differences may be due to potency and pharmacokinetic factors or dissimilar mechanisms of action when the compounds are applied directly to single neurons."}
{"id": "PMID:16998", "title": "Unusual alpha adrenergic receptor potency of methyldopa metabolites on melanocyte function.", "content": "Catecholamines possessing alpha adrenergic receptor agonist properties induce lightening or reverse melanocyte stimulating hormone darkening of frog skin in vitro. The capacity to activate this alpha receptor by the methyldopa metabolites methyldopamine and methylnorepinephrine was compared with the capacity of the naturally occurring dopa metabolites, dopamine and norepinephrine. Melanocyte stimulating hormone-induced darkening or dispersion of the granules was reversed by each of these metabolites. Methylnorepinephrine was 10 times as potent as norepinephrine, and methyldopamine was 30- to 100-fold more potent than the naturally occurring dopamine. These inhibitory effects on melanocyte stimulating hormone could be blocked or partially impaired using the alpha adrenergic blocker, phentolamine. They were not affected by pretreatment of frogs with the monoamine oxidase inhibitor pheniprazine (Catron) nor by the application of pheniprazine, angiotensin or serotonin in vitro. This neuroendocrine model has alpha adrenergic receptor relationships analogous to those described in the central nervous system for methyldopa metabolites.", "contents": "Unusual alpha adrenergic receptor potency of methyldopa metabolites on melanocyte function. Catecholamines possessing alpha adrenergic receptor agonist properties induce lightening or reverse melanocyte stimulating hormone darkening of frog skin in vitro. The capacity to activate this alpha receptor by the methyldopa metabolites methyldopamine and methylnorepinephrine was compared with the capacity of the naturally occurring dopa metabolites, dopamine and norepinephrine. Melanocyte stimulating hormone-induced darkening or dispersion of the granules was reversed by each of these metabolites. Methylnorepinephrine was 10 times as potent as norepinephrine, and methyldopamine was 30- to 100-fold more potent than the naturally occurring dopamine. These inhibitory effects on melanocyte stimulating hormone could be blocked or partially impaired using the alpha adrenergic blocker, phentolamine. They were not affected by pretreatment of frogs with the monoamine oxidase inhibitor pheniprazine (Catron) nor by the application of pheniprazine, angiotensin or serotonin in vitro. This neuroendocrine model has alpha adrenergic receptor relationships analogous to those described in the central nervous system for methyldopa metabolites."}
{"id": "PMID:17000", "title": "Alpha blocking action of the antihypertensive agent, prazosin.", "content": "The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the  hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade.", "contents": "Alpha blocking action of the antihypertensive agent, prazosin. The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the  hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade."}
{"id": "PMID:17001", "title": "Measurement of prostaglandin E2 in an inflammatory exudate: effects of nonsteroidal anti-inflammatory agents.", "content": "A method was developed for extracting and measuring nanogram quantities of prostaglandin E2 (PGE2) from carrageenan-induced abscess in the rat. PGE2 concentration, quantitated by radioimmunoassay, was 42.5 and 92.9 ng/g of abscess in two studies. Anti-inflammatory activity, based on reduction in abscess weight, was observed with indomethacin, phenylbutazone, SC-19220 and A-22981; however, only indomethacin (10 mg/kg i.p.) significantly reduced PGE2 levels in the abscess tissue. Dose-related anti-inflammatory activity of indomethacin (1-10 mg/kg i.p.) was directly correlated with  reductions of PGE2 content in the abscess. These data support the theory that the anti-inflammatory activity of indomethacin in the carrageenan abscess model involves inhibition of prostaglandin formation. Dose-related suppression of abscess formation by SC-19220 (7.5-30 mg/kg i.p.) was not related to changes in PGE2 levels at the inflammatory site, which suggests that the anti-inflammatory mechanism of SC-19220 is not mediated via inhibition of prostaglandin synthesis.", "contents": "Measurement of prostaglandin E2 in an inflammatory exudate: effects of nonsteroidal anti-inflammatory agents. A method was developed for extracting and measuring nanogram quantities of prostaglandin E2 (PGE2) from carrageenan-induced abscess in the rat. PGE2 concentration, quantitated by radioimmunoassay, was 42.5 and 92.9 ng/g of abscess in two studies. Anti-inflammatory activity, based on reduction in abscess weight, was observed with indomethacin, phenylbutazone, SC-19220 and A-22981; however, only indomethacin (10 mg/kg i.p.) significantly reduced PGE2 levels in the abscess tissue. Dose-related anti-inflammatory activity of indomethacin (1-10 mg/kg i.p.) was directly correlated with  reductions of PGE2 content in the abscess. These data support the theory that the anti-inflammatory activity of indomethacin in the carrageenan abscess model involves inhibition of prostaglandin formation. Dose-related suppression of abscess formation by SC-19220 (7.5-30 mg/kg i.p.) was not related to changes in PGE2 levels at the inflammatory site, which suggests that the anti-inflammatory mechanism of SC-19220 is not mediated via inhibition of prostaglandin synthesis."}
{"id": "PMID:17002", "title": "The concentration of ionized magnesium in barnacle muscle fibres.", "content": "1. The total Mg in isolated fibres of Balanus aquila was 10-5 m-mole/kg wet wt. 2. The intracellular free Mg was measured by a null point method using Eriochrome Blue as an indicator of free Mg, and internal dialysis with solutions of varying ionized Mg concentrations. The results indicated a free Mg of 6 mM or 4-2 m-mole/kg wet wt. in the intracellular water immediately surrounding the dialysis capillary. 3. The ATP concentration was estimated to be 4-9 m-mole/kg wet wt. 4. A tentative partitioning of Mg among various intracellular constitutents based on present data combined with published work by others is (m-mole/kg wet wt): free, 4-2; MgATP, 4-2; myofibrillar bound, 1; residual (presumably bound to arginine phosphate and phosphate) ca. 1.", "contents": "The concentration of ionized magnesium in barnacle muscle fibres. 1. The total Mg in isolated fibres of Balanus aquila was 10-5 m-mole/kg wet wt. 2. The intracellular free Mg was measured by a null point method using Eriochrome Blue as an indicator of free Mg, and internal dialysis with solutions of varying ionized Mg concentrations. The results indicated a free Mg of 6 mM or 4-2 m-mole/kg wet wt. in the intracellular water immediately surrounding the dialysis capillary. 3. The ATP concentration was estimated to be 4-9 m-mole/kg wet wt. 4. A tentative partitioning of Mg among various intracellular constitutents based on present data combined with published work by others is (m-mole/kg wet wt): free, 4-2; MgATP, 4-2; myofibrillar bound, 1; residual (presumably bound to arginine phosphate and phosphate) ca. 1."}
{"id": "PMID:17003", "title": "Separative pathways for urea and water, and for chloride in chicken erythrocytes.", "content": "1. Urea and water permeabilities of chicken erythrocytes are considerably lower than those of mammalian red cells. 2. The permeabilities to urea, thiourea and to N-methylurea (about 10(-6) cm/sec at 25 degrees C) were independent of concentration within a very broad range, and we found no evidence of interaction between transport of analogue molecules. The activation energies were between 17 and 19 kcal/mole, and urea transport was not inhibited by phloretin, which inhibits urea transport in mammalian red cells. 3. The water permeability of chicken red cells (as measured by the diffusion of tritiated water) was 1-35 X 10(-3) cm/sec at 25 degrees C. The activation energy was 10 kcal/mole, and the water permeability was not affected by phloretin or parachloromercuribenzoate. 4. It is concluded that the urea and water permeabilities of the chicken erythrocyte membrane are similar to those of a non-porous bimolecular phospholipid membrane. 5. Like the red cells of other animal species the chicken red cell membrane contains an anion transport system, mediating a rapid exchange of chloride across the cell membranes. The pH dependence, temperature dependence, and sensitivity to inhibitors were similar to the properties of the anion transport system found in mammalian red cells. Our study shows, therefore, that the transport system offers a highly specific pathway to the exchange of anions, without presenting an inspecific leak to the permeation of water and urea.", "contents": "Separative pathways for urea and water, and for chloride in chicken erythrocytes. 1. Urea and water permeabilities of chicken erythrocytes are considerably lower than those of mammalian red cells. 2. The permeabilities to urea, thiourea and to N-methylurea (about 10(-6) cm/sec at 25 degrees C) were independent of concentration within a very broad range, and we found no evidence of interaction between transport of analogue molecules. The activation energies were between 17 and 19 kcal/mole, and urea transport was not inhibited by phloretin, which inhibits urea transport in mammalian red cells. 3. The water permeability of chicken red cells (as measured by the diffusion of tritiated water) was 1-35 X 10(-3) cm/sec at 25 degrees C. The activation energy was 10 kcal/mole, and the water permeability was not affected by phloretin or parachloromercuribenzoate. 4. It is concluded that the urea and water permeabilities of the chicken erythrocyte membrane are similar to those of a non-porous bimolecular phospholipid membrane. 5. Like the red cells of other animal species the chicken red cell membrane contains an anion transport system, mediating a rapid exchange of chloride across the cell membranes. The pH dependence, temperature dependence, and sensitivity to inhibitors were similar to the properties of the anion transport system found in mammalian red cells. Our study shows, therefore, that the transport system offers a highly specific pathway to the exchange of anions, without presenting an inspecific leak to the permeation of water and urea."}
{"id": "PMID:17004", "title": "Cell size, macromolecular composition, and O2 consumption during agitated cultivation of Naegleria gruberi.", "content": "Cell size, macromolecular composition, carbohydrate utilization patterns, and O2 concentrations were measured throughout the growth stages of Naegleria gruberi in agitated culture in a complex medium. Biphasic logarithmic growth occurred during the intial 83 hr of growth and the mean generation time was 7.0 hr and 19 hr during initial and secondary log growth stages, respectively. The maximum yield was 5 X 10(6) amebae/ml. The pH rose rapidly (1 pH unit) during the secondary log growth phase (52-83 hr) and continued into the stationary growth phase (83-120 hr). Dry weight, total protein, carbohydrate, and RNA per ameba increased just before the secondary log growth phase. RNA increase 31% to 35% per ameba at the end of each phase of log growth. DNA increased approximately 2-fold throughout the different growth phases. Average cell size increased 90% during biphasic log growth then decreased during stationary phase. O2 tension decreased from 100% to 18% of saturation during the biphasic growth phase, then increased during stationary growth to near 100% saturation. Glucose and total carbohydrate assays showed little utilization of those substrates throughout the growth stages. Naegleria gruberi presumably has a predominantly aerobic metabolism, also its metabolism may change during the different growth phases.", "contents": "Cell size, macromolecular composition, and O2 consumption during agitated cultivation of Naegleria gruberi. Cell size, macromolecular composition, carbohydrate utilization patterns, and O2 concentrations were measured throughout the growth stages of Naegleria gruberi in agitated culture in a complex medium. Biphasic logarithmic growth occurred during the intial 83 hr of growth and the mean generation time was 7.0 hr and 19 hr during initial and secondary log growth stages, respectively. The maximum yield was 5 X 10(6) amebae/ml. The pH rose rapidly (1 pH unit) during the secondary log growth phase (52-83 hr) and continued into the stationary growth phase (83-120 hr). Dry weight, total protein, carbohydrate, and RNA per ameba increased just before the secondary log growth phase. RNA increase 31% to 35% per ameba at the end of each phase of log growth. DNA increased approximately 2-fold throughout the different growth phases. Average cell size increased 90% during biphasic log growth then decreased during stationary phase. O2 tension decreased from 100% to 18% of saturation during the biphasic growth phase, then increased during stationary growth to near 100% saturation. Glucose and total carbohydrate assays showed little utilization of those substrates throughout the growth stages. Naegleria gruberi presumably has a predominantly aerobic metabolism, also its metabolism may change during the different growth phases."}
{"id": "PMID:17006", "title": "Use of 1-anilino-8-naphthalene-sulfonate as a probe of gastric vesicle transport.", "content": "The interaction of 1-anilino-8-naphthalene-sulfonate (ANS) with vesicles derived from hog fundic mucosa was studied in the presence of valinomycin and with the addition of ATP. Evidence was found for two classes of sites, those rapidly accessible to ANS with a KD of 7.5 micronM and those slowly accessible, but rapidly accessed in the presence of valinomycin with a KD of 2.5 micronM. ATP transiently increases the quantum yield of the latter ANS binding sites only in the presence of valinomycin, but does not alter the number of KD of those sites. The time course of this increase correlates with H+ uptake and Rb+ extrusion by those vesicles and H+ carries such as tetrachlorsalicylanilide or nigericin abolish the ATP response. With ATP addition in the presence of SC14N and valinomycin there is transient uptake of SCN-. It is concluded that ANS is acting as a probe of a structural change dependent on a potential and H+ gradient.", "contents": "Use of 1-anilino-8-naphthalene-sulfonate as a probe of gastric vesicle transport. The interaction of 1-anilino-8-naphthalene-sulfonate (ANS) with vesicles derived from hog fundic mucosa was studied in the presence of valinomycin and with the addition of ATP. Evidence was found for two classes of sites, those rapidly accessible to ANS with a KD of 7.5 micronM and those slowly accessible, but rapidly accessed in the presence of valinomycin with a KD of 2.5 micronM. ATP transiently increases the quantum yield of the latter ANS binding sites only in the presence of valinomycin, but does not alter the number of KD of those sites. The time course of this increase correlates with H+ uptake and Rb+ extrusion by those vesicles and H+ carries such as tetrachlorsalicylanilide or nigericin abolish the ATP response. With ATP addition in the presence of SC14N and valinomycin there is transient uptake of SCN-. It is concluded that ANS is acting as a probe of a structural change dependent on a potential and H+ gradient."}
{"id": "PMID:17007", "title": "Cation transport by gastric H+:K+ ATPase.", "content": "A vesicular microsomal fraction isolated from hog fundic mucosa demonstrates the capacity to take up equal amounts of RB+ and Cl-. The amount of the Rb+ uptake is sensitive to the extravesicular osmolarity, and rate of uptake is sensitive to temperature. 86Rb+ efflux is dependent upon the cation composition of the diluting solution. ATP, but not beta-gamma methylene ATP, induces a reversible efflux of 86Rb+ from loaded vesicles, and this is dependent upon a functional K+-ATPase. The ATP induced efflux is not affected by CCCP (carbonyl cyanide m-chlorophenylhydrazone) or TCS (tetrachlorosalicylanilide) nor by lipid soluble ions or valinomycin. Nigericin inhibits the efflux by 40%. Uptake of the lipid soluble ion 14C-SCN- has been demonstrated and is enhanced by ATP only in the presence of valinomycin. The results are consistent with a neutral or isopotential exchange of H+ for Rb+ mediated by K+-ATPase.", "contents": "Cation transport by gastric H+:K+ ATPase. A vesicular microsomal fraction isolated from hog fundic mucosa demonstrates the capacity to take up equal amounts of RB+ and Cl-. The amount of the Rb+ uptake is sensitive to the extravesicular osmolarity, and rate of uptake is sensitive to temperature. 86Rb+ efflux is dependent upon the cation composition of the diluting solution. ATP, but not beta-gamma methylene ATP, induces a reversible efflux of 86Rb+ from loaded vesicles, and this is dependent upon a functional K+-ATPase. The ATP induced efflux is not affected by CCCP (carbonyl cyanide m-chlorophenylhydrazone) or TCS (tetrachlorosalicylanilide) nor by lipid soluble ions or valinomycin. Nigericin inhibits the efflux by 40%. Uptake of the lipid soluble ion 14C-SCN- has been demonstrated and is enhanced by ATP only in the presence of valinomycin. The results are consistent with a neutral or isopotential exchange of H+ for Rb+ mediated by K+-ATPase."}
{"id": "PMID:17008", "title": "Characterization of bile acid binding to rat intestinal brush border membranes.", "content": "Studies were performed to characterize the binding1 of bile acids to intestinal brush border membranes. Total 14C-taurodeoxycholate binding was: 1) similar for brush borders prepared from jejunum and ileum, 2) linear with respect to monomer concentration, 3) uninhibited by a structural analog, and 4) not depressed by boiling or trypsin. A linear relationship existed between binding and the number of hydrogen bonds formed by a bile acid and the slope of the line corresponded to delta deltaF of 300 cal/mol. The binding of bile acids to the 105,000 x g supernatant fraction of sonicated brush borders was similar to the binding of phospholipid liposomes using gel chromatography. These data suggest that: 1) the kinetics and characteristics of binding of bile acid to ileal brush borders do not reflect the kinetics and characteristics of active ileal transport previously obtained in whole tissue preparations, but instead reflect the kinetics and characteristics of passive jejunal transport; 2) a determinant of binding is hydrogen bonding with water; 3) isolated intact brush borders are relatively polar membranes; and 4) binding to solubilized brush borders may represent partitioning between the aqueous phase and membrane lipid.", "contents": "Characterization of bile acid binding to rat intestinal brush border membranes. Studies were performed to characterize the binding1 of bile acids to intestinal brush border membranes. Total 14C-taurodeoxycholate binding was: 1) similar for brush borders prepared from jejunum and ileum, 2) linear with respect to monomer concentration, 3) uninhibited by a structural analog, and 4) not depressed by boiling or trypsin. A linear relationship existed between binding and the number of hydrogen bonds formed by a bile acid and the slope of the line corresponded to delta deltaF of 300 cal/mol. The binding of bile acids to the 105,000 x g supernatant fraction of sonicated brush borders was similar to the binding of phospholipid liposomes using gel chromatography. These data suggest that: 1) the kinetics and characteristics of binding of bile acid to ileal brush borders do not reflect the kinetics and characteristics of active ileal transport previously obtained in whole tissue preparations, but instead reflect the kinetics and characteristics of passive jejunal transport; 2) a determinant of binding is hydrogen bonding with water; 3) isolated intact brush borders are relatively polar membranes; and 4) binding to solubilized brush borders may represent partitioning between the aqueous phase and membrane lipid."}
{"id": "PMID:17009", "title": "Purple membrane vesicles: morphology and proton translocation.", "content": "Purple membrane vesicles prepared by different techniques differ widely in their morphology and ability to establish a proton gradient in the light. The procedures used to prepare active vesicles do not completely dissociate the purple membrane and thus preserve a preferential orientation of the protein, while most of the lipid is exchanged for added lipid. Responses to illumination are largely determined by the size of the vesicles and the degree to which bacteriorhodopsin is preferentially oriented. Any attempt to compare the interaction of different lipids with bacteriorhodopsin by measuring the pH response must take these factors into account. With an improved technique we have obtained vesicles of rather uniform size and bacteriorhodopsin orientation, which accumulate protons with an initial rate of 160 ng H+ sec-1 mg-1 protein at light intensities of 10(6) erg cm-2 sec-1. The kinetics of the process are complex and at present insufficiently understood.", "contents": "Purple membrane vesicles: morphology and proton translocation. Purple membrane vesicles prepared by different techniques differ widely in their morphology and ability to establish a proton gradient in the light. The procedures used to prepare active vesicles do not completely dissociate the purple membrane and thus preserve a preferential orientation of the protein, while most of the lipid is exchanged for added lipid. Responses to illumination are largely determined by the size of the vesicles and the degree to which bacteriorhodopsin is preferentially oriented. Any attempt to compare the interaction of different lipids with bacteriorhodopsin by measuring the pH response must take these factors into account. With an improved technique we have obtained vesicles of rather uniform size and bacteriorhodopsin orientation, which accumulate protons with an initial rate of 160 ng H+ sec-1 mg-1 protein at light intensities of 10(6) erg cm-2 sec-1. The kinetics of the process are complex and at present insufficiently understood."}
{"id": "PMID:17014", "title": "Effect of pH on hyperthermic cell survival.", "content": "Chinese hamster ovary cells incubated with various concentrations of CO2, to obtain extracellular pH values in the range of 6.40-7.85, were heated at 45.5C for 5, 10, or 20 minutes. Thermal sensitivity increased sharply from pH 7.35 to 6.65 (i.e., survival decreased from 1 X 10(-2) to 3 X 10(-5) for 20 minutes of heating), but remained constant from pH 7.35 to 7.85. The enhanced thermal sensitivity at pH values below pth 7.35 suggested that tumors should be preferentially destroyed by heat relative to normal tissue, since reports indicated that tumors were more acidic than the surrounding normal tissue.", "contents": "Effect of pH on hyperthermic cell survival. Chinese hamster ovary cells incubated with various concentrations of CO2, to obtain extracellular pH values in the range of 6.40-7.85, were heated at 45.5C for 5, 10, or 20 minutes. Thermal sensitivity increased sharply from pH 7.35 to 6.65 (i.e., survival decreased from 1 X 10(-2) to 3 X 10(-5) for 20 minutes of heating), but remained constant from pH 7.35 to 7.85. The enhanced thermal sensitivity at pH values below pth 7.35 suggested that tumors should be preferentially destroyed by heat relative to normal tissue, since reports indicated that tumors were more acidic than the surrounding normal tissue."}
{"id": "PMID:17015", "title": "Aryl and heterocyclic diazo compounds as potential environmental electrophiles.", "content": "4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard.", "contents": "Aryl and heterocyclic diazo compounds as potential environmental electrophiles. 4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard."}
{"id": "PMID:17017", "title": "Mosquito transmission of wild turkey malaria, Plasmodium hermani.", "content": "Culex nigripalpus experimentally transmitted Plasmodium hermani, a plasmodium of wild turkeys (Meleagris gallopavo) in Florida. The mosquitoes were infected by feeding upon blood induced parasitemias in domestic turkey poults. The resulting sporozoites, transmitted by either mosquito bites or injection, produced malaria infections in domestic poults.", "contents": "Mosquito transmission of wild turkey malaria, Plasmodium hermani. Culex nigripalpus experimentally transmitted Plasmodium hermani, a plasmodium of wild turkeys (Meleagris gallopavo) in Florida. The mosquitoes were infected by feeding upon blood induced parasitemias in domestic turkey poults. The resulting sporozoites, transmitted by either mosquito bites or injection, produced malaria infections in domestic poults."}
{"id": "PMID:17018", "title": "Nosocomial bacteremia. Potential for prevention of procedure-related cases.", "content": "During a six-month period, 187 inpatients had bacteremia associated with community-acquired infection and 91 patients had bacteremia from a nosocomial infection. The most frequently identified sites of infection in both types of bacteremia were the respiratory and urinary tracts. Escherichia coli and Diplococcus pneumoniae were the organisms most frequently isolated from cultures of patients with community-acquired bacteremia, and E coli, Staphylococcus aureus, and Klebsiella were most frequently isolated from patients with nosocomial bacteremia. Bacteremic nosocomial infections were related to urinary catheters, respiratory and intravenous therapy, or hyperalimentation in 32 of the 91 cases. Even assuming the unproved hypotheses that rigid adherence to current guidelines would prevent all of these procedure-related cases, 59 cases of bacteremia would still have occurred. This emphasizes the need for further research into prevention of nosocomial infection.", "contents": "Nosocomial bacteremia. Potential for prevention of procedure-related cases. During a six-month period, 187 inpatients had bacteremia associated with community-acquired infection and 91 patients had bacteremia from a nosocomial infection. The most frequently identified sites of infection in both types of bacteremia were the respiratory and urinary tracts. Escherichia coli and Diplococcus pneumoniae were the organisms most frequently isolated from cultures of patients with community-acquired bacteremia, and E coli, Staphylococcus aureus, and Klebsiella were most frequently isolated from patients with nosocomial bacteremia. Bacteremic nosocomial infections were related to urinary catheters, respiratory and intravenous therapy, or hyperalimentation in 32 of the 91 cases. Even assuming the unproved hypotheses that rigid adherence to current guidelines would prevent all of these procedure-related cases, 59 cases of bacteremia would still have occurred. This emphasizes the need for further research into prevention of nosocomial infection."}
{"id": "PMID:17020", "title": "Costs and outcomes for different primary care providers.", "content": "This study examined the relationship between levels of medical training and direct costs for 1,700 episodes of acute illness treated in ambulatory-care clinics. Faculty, family practice residents, and physician assistants were included as the providers. Total cost and four component costs were examined. An outcome was defined as good if the patient returned to his usual level of functioning after an acute illness episode. Average total cost per episode was not related to type of provider, but there were significant (P less than .05) differences among providers in laboratory and medication costs. Faculty and physician assistants produced higher costs, especially for patients who experienced bad outcomes. Both costs and percentage of good outcomes achieved were similar in first-, second-, and third-year residents.", "contents": "Costs and outcomes for different primary care providers. This study examined the relationship between levels of medical training and direct costs for 1,700 episodes of acute illness treated in ambulatory-care clinics. Faculty, family practice residents, and physician assistants were included as the providers. Total cost and four component costs were examined. An outcome was defined as good if the patient returned to his usual level of functioning after an acute illness episode. Average total cost per episode was not related to type of provider, but there were significant (P less than .05) differences among providers in laboratory and medication costs. Faculty and physician assistants produced higher costs, especially for patients who experienced bad outcomes. Both costs and percentage of good outcomes achieved were similar in first-, second-, and third-year residents."}
{"id": "PMID:17021", "title": "[In vitro examination on antibacterial activity of ciclacillin (ACPC) against clinically isolated strains (author's transl)].", "content": "(1) The antibacterial acivity of ciclacillin (ACPC) with inoculum size of 10(6) cells/ml was four times less potent than that of ampicillin (ABPC) and 4 approximately 8 times less potent than that of AMPC, but was 4 approximately 8 times more potent than that of CEX against Streptococcus pyogenes. For Streptococcus pneumoniae, ACPC was 2 approximately 4 times less active than ABPC and AMPC, but 16 approximately 32 times more active than CEX. Staphylococcus aureus was 4 approximately 8 times less susceptible to ACPC than to ABPC and AMPC, but 1 approximately 2 times more susceptible than to CEX. Against E. coli, ACPC was as active as CEX, 2 approximately 4 times less active than ABPC, and 4 approximately 8 times less active than AMPC. (2) It was suposed that ACPC was more resistant to penicillinase and more antibacterial with inoculum size of 10(6) cells/ml cells/ml than with 10(6) cells/ml. ACPC was 4 approximately 8 times less active than ABPC, and AMPC against Staphylococcus aureus with 10(8) cells/ml, while with 10(6) cells/ml, it was 2 times less active than ABPC and AMPC. (3) ACPC-resistant strains (greater than or equal to 3.13 microng/ml) of Streptococcus pyogenes and Streptococcus pneumoniae were not found. (4) A difference was noted in MIC of three semi-synthetic penicillins, ACPC, ABPC and AMPC, against Staphylococcus aureus, and E. coli between the sources from which their strains were isolated. (5) There were many strains resistant to erythromycin (EM) and josamycin (JM) (greater than 60%, respectively to both antibiotics) in Stretpococcus pyogenes and pus-isolated Staphylococcus aureus. No strains of Streptococcus pyogenes, were found resistant to EM and JM.", "contents": "[In vitro examination on antibacterial activity of ciclacillin (ACPC) against clinically isolated strains (author's transl)]. (1) The antibacterial acivity of ciclacillin (ACPC) with inoculum size of 10(6) cells/ml was four times less potent than that of ampicillin (ABPC) and 4 approximately 8 times less potent than that of AMPC, but was 4 approximately 8 times more potent than that of CEX against Streptococcus pyogenes. For Streptococcus pneumoniae, ACPC was 2 approximately 4 times less active than ABPC and AMPC, but 16 approximately 32 times more active than CEX. Staphylococcus aureus was 4 approximately 8 times less susceptible to ACPC than to ABPC and AMPC, but 1 approximately 2 times more susceptible than to CEX. Against E. coli, ACPC was as active as CEX, 2 approximately 4 times less active than ABPC, and 4 approximately 8 times less active than AMPC. (2) It was suposed that ACPC was more resistant to penicillinase and more antibacterial with inoculum size of 10(6) cells/ml cells/ml than with 10(6) cells/ml. ACPC was 4 approximately 8 times less active than ABPC, and AMPC against Staphylococcus aureus with 10(8) cells/ml, while with 10(6) cells/ml, it was 2 times less active than ABPC and AMPC. (3) ACPC-resistant strains (greater than or equal to 3.13 microng/ml) of Streptococcus pyogenes and Streptococcus pneumoniae were not found. (4) A difference was noted in MIC of three semi-synthetic penicillins, ACPC, ABPC and AMPC, against Staphylococcus aureus, and E. coli between the sources from which their strains were isolated. (5) There were many strains resistant to erythromycin (EM) and josamycin (JM) (greater than 60%, respectively to both antibiotics) in Stretpococcus pyogenes and pus-isolated Staphylococcus aureus. No strains of Streptococcus pyogenes, were found resistant to EM and JM."}
{"id": "PMID:17025", "title": "Effects of metiamide and propranolol on gastric secretion in anesthetized dogs.", "content": "The effects of metiamide, a histamine H2-receptor antagonist, and propranolol, a beta-adrenergic blocking agent, on gastric secretion were studied in anesthetized dogs. Metiamide, 1.45 mg/kg i.v., markedly inhibited the gastric secretion induced by a continuous i.v. infusion of tetragastrin (8 microng/kg-hr), histamine dihydrochloride (160 microng/kg-hr), or methacholine bromide (100 microng/kg-hr). Propranolol 0.5 or 1.0 mg/kg i.v. produced a significant potentiation of tetragastrin-induced gastric secretion but no influence of the secretion induced by methacholine. Propranolol at 5 or 10 mg/kg i.v. produced a slight reduction of the tetragastrin-induced secretion and a significant reduction of methacholine-induced secretion. Histamine-induced gastric secretion was not affected by propranolol at either 1 and 10 mg/kg i.v. These findings lend support to the hypothesis that interactions among histamine, gastrin and acetylcholine receptors do occur though the degree would not be the same in all directions.", "contents": "Effects of metiamide and propranolol on gastric secretion in anesthetized dogs. The effects of metiamide, a histamine H2-receptor antagonist, and propranolol, a beta-adrenergic blocking agent, on gastric secretion were studied in anesthetized dogs. Metiamide, 1.45 mg/kg i.v., markedly inhibited the gastric secretion induced by a continuous i.v. infusion of tetragastrin (8 microng/kg-hr), histamine dihydrochloride (160 microng/kg-hr), or methacholine bromide (100 microng/kg-hr). Propranolol 0.5 or 1.0 mg/kg i.v. produced a significant potentiation of tetragastrin-induced gastric secretion but no influence of the secretion induced by methacholine. Propranolol at 5 or 10 mg/kg i.v. produced a slight reduction of the tetragastrin-induced secretion and a significant reduction of methacholine-induced secretion. Histamine-induced gastric secretion was not affected by propranolol at either 1 and 10 mg/kg i.v. These findings lend support to the hypothesis that interactions among histamine, gastrin and acetylcholine receptors do occur though the degree would not be the same in all directions."}
{"id": "PMID:17026", "title": "Descending release of acetylcholine from the locally distended guinea pig ileum.", "content": "The effects of local distension of the intestinal wall on the release of acetylcholine (ACh) from the adjacent non-distended part were studied with the segment os isolated guinea pig ileum. Local distension of the intestinal wall induced the increased release of ACh in the distended part and in its anal side but not in its oral side. Such aboral release of ACh by local distension was abolished by tetrodotoxin or atropine in the concentrations which did not block the release in the distended part. When hexamethonium was applied exclusively to the distending part, significant increase of ACh release was observed in both the regions oral to and anal to the distended part. It is suggested that distension stimuli applied to the myenteric plexus are transmitted aborally along the network of the Auerbach's plexus to the anal direction. The release of ACh from the intestine by nicotine or DMPP differed from the occurring during local distension in that the release was localized to the part of the intestine to which the drug was applied.", "contents": "Descending release of acetylcholine from the locally distended guinea pig ileum. The effects of local distension of the intestinal wall on the release of acetylcholine (ACh) from the adjacent non-distended part were studied with the segment os isolated guinea pig ileum. Local distension of the intestinal wall induced the increased release of ACh in the distended part and in its anal side but not in its oral side. Such aboral release of ACh by local distension was abolished by tetrodotoxin or atropine in the concentrations which did not block the release in the distended part. When hexamethonium was applied exclusively to the distending part, significant increase of ACh release was observed in both the regions oral to and anal to the distended part. It is suggested that distension stimuli applied to the myenteric plexus are transmitted aborally along the network of the Auerbach's plexus to the anal direction. The release of ACh from the intestine by nicotine or DMPP differed from the occurring during local distension in that the release was localized to the part of the intestine to which the drug was applied."}
{"id": "PMID:17028", "title": "Purification of histamine receptor. (IV) Specificity of binding of various drugs to the histamine receptor-rich fraction and to solubilized binding sites.", "content": "Studies were made on tritiated histamine binding to the receptor-rich membrane fraction and solubilized sites and its displacement by various drugs. H1-Agonists and antagonists displaced histamine most effectively. A H2-agonist and atropine were less effective and propranolol, phentolamine and imidazole acetic acid had little effect. The solubilized binding sites showed the same specificity of binding as the membrane fraction. Membrane fragments had two binding constants, whereas solubilized sites had only one. Solubilized sites bound similar amounts of histamine and dibenamine: the latter was applied to intact tissue under conditions which would presumably cause specific binding to histamine receptors. These binding characteristics show that the method used was adequate for purification of histamine receptors from smooth muscle of cat small intestine.", "contents": "Purification of histamine receptor. (IV) Specificity of binding of various drugs to the histamine receptor-rich fraction and to solubilized binding sites. Studies were made on tritiated histamine binding to the receptor-rich membrane fraction and solubilized sites and its displacement by various drugs. H1-Agonists and antagonists displaced histamine most effectively. A H2-agonist and atropine were less effective and propranolol, phentolamine and imidazole acetic acid had little effect. The solubilized binding sites showed the same specificity of binding as the membrane fraction. Membrane fragments had two binding constants, whereas solubilized sites had only one. Solubilized sites bound similar amounts of histamine and dibenamine: the latter was applied to intact tissue under conditions which would presumably cause specific binding to histamine receptors. These binding characteristics show that the method used was adequate for purification of histamine receptors from smooth muscle of cat small intestine."}
{"id": "PMID:17031", "title": "[Acquired colour-vision-deficiencies caused by side-effects of pharmacotherapy (author's transl)].", "content": "Acquired colour-vision deficiencies are an early indicator for drug-induced retinopathy as well as drug-induced retrobulbar neuritis. Koellner's rule, which says, that damage of the retina induces a tritan-defect, and damage of the optic nerve induce a red-green-defect is also valid for defects secondary to drug-toxicity. Pseudoisochromatic plates, anomaloscope and other tests (Panel D-15-test) have to be selected correspondingly to use them as screening-methods.", "contents": "[Acquired colour-vision-deficiencies caused by side-effects of pharmacotherapy (author's transl)]. Acquired colour-vision deficiencies are an early indicator for drug-induced retinopathy as well as drug-induced retrobulbar neuritis. Koellner's rule, which says, that damage of the retina induces a tritan-defect, and damage of the optic nerve induce a red-green-defect is also valid for defects secondary to drug-toxicity. Pseudoisochromatic plates, anomaloscope and other tests (Panel D-15-test) have to be selected correspondingly to use them as screening-methods."}
{"id": "PMID:17032", "title": "beta-Adrenergic receptors in rat kidney: direct localization by a fluorescent beta-blocker.", "content": "A new fluorescent beta-adrenergic blocker, 9-amino-acridin propranolol (9-AAP), was administered intravenously to albino rats. Fluorescent aggregates of 9-AAP binding sites were concentrated in the vascular poles of the glomeruli in association with the preglomerular afferent arterioles. 9-AAP fluorescence was reduced following pretreatment with (+/-)- and (-)-propranolol and was less affected in rats pretreated by the (+)-racemic isomer. 9-AAP binding sites were also observed on the lining epithelium of the renal collecting system. Our data suggest that 9-AAP may label beta-adrenergic receptors in rat kidney.", "contents": "beta-Adrenergic receptors in rat kidney: direct localization by a fluorescent beta-blocker. A new fluorescent beta-adrenergic blocker, 9-amino-acridin propranolol (9-AAP), was administered intravenously to albino rats. Fluorescent aggregates of 9-AAP binding sites were concentrated in the vascular poles of the glomeruli in association with the preglomerular afferent arterioles. 9-AAP fluorescence was reduced following pretreatment with (+/-)- and (-)-propranolol and was less affected in rats pretreated by the (+)-racemic isomer. 9-AAP binding sites were also observed on the lining epithelium of the renal collecting system. Our data suggest that 9-AAP may label beta-adrenergic receptors in rat kidney."}
{"id": "PMID:17033", "title": "Ultrastructural localization of calcium in normal and abnormal skeletal muscle.", "content": "Calcium was demonstrated ultrastructurally as a fine black reaction product with unbuffered 2% saturated potassium pyroantimonate, pH 9.4. In comparison with normal muscle, there was increased precipitate in degenerating skeletal muscle fibers and some degenerating-regenerating fibers occurring in pathologic human muscle, regardless of disease entity, and in experimentally injured rat muscle. The pathologically increased calcium was mainly within the sarcoplasmic reticulum and mitochondria. Both structures could be completely blackened. Nuclear calcium was also increased, the precipitates being localized as circular profiles within the nucleoli and heterochromatin as well as being associated with the nuclear envelope. Myofibrillar calcium was only modestly increased. When normal rat muscle was preincubated in 136 mM calcium-enhanced Hanks' medium, calcium accumulated in the muscle fibers--it was especially heavy in the mitochondria and sarcoplasmic reticulum and appeared identical with the pathologic human and rat muscle fibers. Preincubation of normal rat muscle in 0.1 M acetate buffer (pH 4.65) before calcium loading augmented myofibrillar staining, mainly in the H-zone of the A-bands excluding the M-zone and in broad irregular N1, N2, and \"N3\" lines of the I-bands. EMMA-4 electron probe microanalysis and EGTA (ethylene glycolbis (beta-aminoethyl ether)N,N'-tetraacetic acid) chelation prior to staining confirmed that the precipitate in the several loci was calcium antimonate. It is proposed that in skeletal muscle fibers injured by various pathologic processes, a breach of the plasmalemma barrier to calcium occurs as a very early abnormality. Extracellular calcium would then pour into the aqueous sarcoplasm of the muscle fiber, from which it would be withdrawn by and accumulated with the still active organelles normally having a great avidity for uptake of this ion, especially the mitochondria and sarcoplasmic reticulum. The resultant organellar calcification would impair function and damage the structure of proteins and phospholipids.", "contents": "Ultrastructural localization of calcium in normal and abnormal skeletal muscle. Calcium was demonstrated ultrastructurally as a fine black reaction product with unbuffered 2% saturated potassium pyroantimonate, pH 9.4. In comparison with normal muscle, there was increased precipitate in degenerating skeletal muscle fibers and some degenerating-regenerating fibers occurring in pathologic human muscle, regardless of disease entity, and in experimentally injured rat muscle. The pathologically increased calcium was mainly within the sarcoplasmic reticulum and mitochondria. Both structures could be completely blackened. Nuclear calcium was also increased, the precipitates being localized as circular profiles within the nucleoli and heterochromatin as well as being associated with the nuclear envelope. Myofibrillar calcium was only modestly increased. When normal rat muscle was preincubated in 136 mM calcium-enhanced Hanks' medium, calcium accumulated in the muscle fibers--it was especially heavy in the mitochondria and sarcoplasmic reticulum and appeared identical with the pathologic human and rat muscle fibers. Preincubation of normal rat muscle in 0.1 M acetate buffer (pH 4.65) before calcium loading augmented myofibrillar staining, mainly in the H-zone of the A-bands excluding the M-zone and in broad irregular N1, N2, and \"N3\" lines of the I-bands. EMMA-4 electron probe microanalysis and EGTA (ethylene glycolbis (beta-aminoethyl ether)N,N'-tetraacetic acid) chelation prior to staining confirmed that the precipitate in the several loci was calcium antimonate. It is proposed that in skeletal muscle fibers injured by various pathologic processes, a breach of the plasmalemma barrier to calcium occurs as a very early abnormality. Extracellular calcium would then pour into the aqueous sarcoplasm of the muscle fiber, from which it would be withdrawn by and accumulated with the still active organelles normally having a great avidity for uptake of this ion, especially the mitochondria and sarcoplasmic reticulum. The resultant organellar calcification would impair function and damage the structure of proteins and phospholipids."}
{"id": "PMID:17038", "title": "[Prolongated amnesia after \"rohypnol\" i.v. before local anesthesia and responsiveness during operation (author's transl)].", "content": "An up-to-eight-hour lasting anterograde amnesia is achieved by \"Rohypnol\" i.v. causing no excitation before local anesthesia is given (prolongation by analgetics, anesthetics, neuroleptics). The cardiovascular functions remain stable with spontaneous breathing and preservation of the swallow and coughing reflexes. During the operation the patient is responsive and cooperative. The patient answers all questions, moves his body into any wanted position and when ordered he performs Valsalva's manoeuver without any remembrane. If not spoken to and having no pain he falls asleep right away. Postoperative vomiting is reduced. The patient feels relaxed after waking up. No complications have been noticed during more than 500 operations. The later questioning of all patients showed only 4 patients (with unsufficient preoperative sedation) who could remember part of the terminal phase of the operation.", "contents": "[Prolongated amnesia after \"rohypnol\" i.v. before local anesthesia and responsiveness during operation (author's transl)]. An up-to-eight-hour lasting anterograde amnesia is achieved by \"Rohypnol\" i.v. causing no excitation before local anesthesia is given (prolongation by analgetics, anesthetics, neuroleptics). The cardiovascular functions remain stable with spontaneous breathing and preservation of the swallow and coughing reflexes. During the operation the patient is responsive and cooperative. The patient answers all questions, moves his body into any wanted position and when ordered he performs Valsalva's manoeuver without any remembrane. If not spoken to and having no pain he falls asleep right away. Postoperative vomiting is reduced. The patient feels relaxed after waking up. No complications have been noticed during more than 500 operations. The later questioning of all patients showed only 4 patients (with unsufficient preoperative sedation) who could remember part of the terminal phase of the operation."}
{"id": "PMID:17048", "title": "Effect of chlorhexidine on plaque development in an artificial mouth.", "content": "The effect of chlorhexidine on the development of plaque, resulting from the inoculation with saliva of a tooth mounted in an artificial mouth, has been studied. The agent delayed the formation of plaque and also inhibited changes in pH and Eh, whether sucrose was present or not. Applied as a rinse at intervals of 12 h it prevented formation of plaque and pH and Eh remained constant. Moreover, chlorhexidine inhibited pH and Eh changes in established plaque. A single application of a gel containing chlorhexidine also greatly inhibited plaque development.", "contents": "Effect of chlorhexidine on plaque development in an artificial mouth. The effect of chlorhexidine on the development of plaque, resulting from the inoculation with saliva of a tooth mounted in an artificial mouth, has been studied. The agent delayed the formation of plaque and also inhibited changes in pH and Eh, whether sucrose was present or not. Applied as a rinse at intervals of 12 h it prevented formation of plaque and pH and Eh remained constant. Moreover, chlorhexidine inhibited pH and Eh changes in established plaque. A single application of a gel containing chlorhexidine also greatly inhibited plaque development."}
{"id": "PMID:17049", "title": "A microcalorimetric study of the growth of Klebsiella aerogenes in simple salts/glucose media.", "content": "Heat output-time records or 'thermograms' produced during the aerobic growth of Klebsiella aerogenes in simple salts/glucose media with growth limiting glucose concentrations of 2.0, 1.0 and 0.5 g dm-3 were obtained using a flow-microcalorimeter fitted with an aerobic cell. These traces are interpreted in terms of the recorded oxygen tension, pH, glucose concentration and bacterial population of the culture. Heat output is greatest during the phase of exponential growth, indicating that here the organisms are most energetically inefficient. During the stationary phase aerobic processes, which give rise to a low oxygen tension, produce a smaller heat output until secondary metabolic processes are complete.", "contents": "A microcalorimetric study of the growth of Klebsiella aerogenes in simple salts/glucose media. Heat output-time records or 'thermograms' produced during the aerobic growth of Klebsiella aerogenes in simple salts/glucose media with growth limiting glucose concentrations of 2.0, 1.0 and 0.5 g dm-3 were obtained using a flow-microcalorimeter fitted with an aerobic cell. These traces are interpreted in terms of the recorded oxygen tension, pH, glucose concentration and bacterial population of the culture. Heat output is greatest during the phase of exponential growth, indicating that here the organisms are most energetically inefficient. During the stationary phase aerobic processes, which give rise to a low oxygen tension, produce a smaller heat output until secondary metabolic processes are complete."}
{"id": "PMID:17065", "title": "Studies of yeast alcohol dehydrogenase with 3-aminopyridine monucleotide.", "content": "3-Aminopyridine mononucleotide, a nicotinamide mononucleotide analog, was prepared by enzymatic cleavage of 3-aminopyridine adenine dinucleotide by a snake venom phosphodiesterase and isolated by means of ion exchange chromatography. The spectrophotometric and fluorometric properties of this analog were studied. Several anions were shown to quench the fluorescence intensity of this analog. pH was shown to have a pronounced effect on the fluorescence intensity. 3-Aminopyridine mononucleotide was shown to be a coenzyme-competitive inhibitor of yeast alcohol dehydrogenase. The 3-aminopyridine mononucleotide was diazotized with the use of nitrous acid. A time dependent irreversible inactivation of yeast alcohol dehydrogenase resulted from incubation with the diazotized 3-aminopyridine mononucleotide at pH 7.0. Incubation of the enzyme with NAD prior to the addition of the diazotized 3-aminopyridine mononucleotid protected the enzyme against inactivation.", "contents": "Studies of yeast alcohol dehydrogenase with 3-aminopyridine monucleotide. 3-Aminopyridine mononucleotide, a nicotinamide mononucleotide analog, was prepared by enzymatic cleavage of 3-aminopyridine adenine dinucleotide by a snake venom phosphodiesterase and isolated by means of ion exchange chromatography. The spectrophotometric and fluorometric properties of this analog were studied. Several anions were shown to quench the fluorescence intensity of this analog. pH was shown to have a pronounced effect on the fluorescence intensity. 3-Aminopyridine mononucleotide was shown to be a coenzyme-competitive inhibitor of yeast alcohol dehydrogenase. The 3-aminopyridine mononucleotide was diazotized with the use of nitrous acid. A time dependent irreversible inactivation of yeast alcohol dehydrogenase resulted from incubation with the diazotized 3-aminopyridine mononucleotide at pH 7.0. Incubation of the enzyme with NAD prior to the addition of the diazotized 3-aminopyridine mononucleotid protected the enzyme against inactivation."}
{"id": "PMID:17066", "title": "[Vaccination complications after oral poliomyelitis vaccination (author's transl)].", "content": "A vaccination complication is only to be recognized if, taking into consideration the incubation time, the clinical picture coincides with that of spontaneous poliomyelitis. Apart from exceptional cases, virological studies are only of importance for the assessment if they are carried out in the acute or subacute stages. Only six out of more than 150 cases could be accepted as vaccination complications.", "contents": "[Vaccination complications after oral poliomyelitis vaccination (author's transl)]. A vaccination complication is only to be recognized if, taking into consideration the incubation time, the clinical picture coincides with that of spontaneous poliomyelitis. Apart from exceptional cases, virological studies are only of importance for the assessment if they are carried out in the acute or subacute stages. Only six out of more than 150 cases could be accepted as vaccination complications."}
{"id": "PMID:17067", "title": "Chronic urticaria as a manifestation of necrotizing venulitis.", "content": "In a group of patients with a syndrome consisting of recurrent episodes of urticaria, arthralgia, abdominal pain, and (rarely) glomerulonephritis, examination of skin biopsy specimens showed necrotizing venulitis. An elevated erythrocyte sedimentation rate was the most common laboratory abnormality. Analyses of serum immunoglobulins revealed random abnormalities of immunoglobulin levels, and assessment of the complement system showed two groups of patients--some with hypocomplementemia and others with a normal complement system. In those with hypocomplementemia, there were low levels of C1q, C4 and, occasionally, C3, compatible with activation of the classic complement pathway. Although the cause of this syndrome is unknown, the complement profiles suggest that more than one mechanism of vascular damage may be operative.", "contents": "Chronic urticaria as a manifestation of necrotizing venulitis. In a group of patients with a syndrome consisting of recurrent episodes of urticaria, arthralgia, abdominal pain, and (rarely) glomerulonephritis, examination of skin biopsy specimens showed necrotizing venulitis. An elevated erythrocyte sedimentation rate was the most common laboratory abnormality. Analyses of serum immunoglobulins revealed random abnormalities of immunoglobulin levels, and assessment of the complement system showed two groups of patients--some with hypocomplementemia and others with a normal complement system. In those with hypocomplementemia, there were low levels of C1q, C4 and, occasionally, C3, compatible with activation of the classic complement pathway. Although the cause of this syndrome is unknown, the complement profiles suggest that more than one mechanism of vascular damage may be operative."}
{"id": "PMID:17069", "title": "Isolation of Histoplasma capsulatum from soil in the Aguas Buenos Caves, Aguas Buenos, Puerto Rico. I. An ecological approach.", "content": "Only one out of 19 soil sampling sites chosen for isolation of H. capsulatum studies yielded positive results. The stations were located in Cueva Oscura, which is part of the Aguas Buenas Caves system. The habitat characteristics of these station are believed to be responsible for the presence of the fungus.", "contents": "Isolation of Histoplasma capsulatum from soil in the Aguas Buenos Caves, Aguas Buenos, Puerto Rico. I. An ecological approach. Only one out of 19 soil sampling sites chosen for isolation of H. capsulatum studies yielded positive results. The stations were located in Cueva Oscura, which is part of the Aguas Buenas Caves system. The habitat characteristics of these station are believed to be responsible for the presence of the fungus."}
{"id": "PMID:17072", "title": "X-ray study of the lithium complex of NAD.", "content": "The Li+-NAD+ complex exists as a 'dimer' of two molecules arranged head-to-tail with Li+ coordinated tetrahedrally to adenine N(7) and three pyrophosphate oxygens. Adenine is stacked intermolecularly on nicotinamide. The conformation of NAD+ is 'extended' and similar to that found in holoenzyme complexes. This is in contrast to the 'folded' structure proposed from spectroscopic studies.", "contents": "X-ray study of the lithium complex of NAD. The Li+-NAD+ complex exists as a 'dimer' of two molecules arranged head-to-tail with Li+ coordinated tetrahedrally to adenine N(7) and three pyrophosphate oxygens. Adenine is stacked intermolecularly on nicotinamide. The conformation of NAD+ is 'extended' and similar to that found in holoenzyme complexes. This is in contrast to the 'folded' structure proposed from spectroscopic studies."}
{"id": "PMID:17084", "title": "Effect of pyridoxine on the growth of Morris hepatoma No. 7288Ctc and enzyme activity.", "content": "The effect(s) of lack of dietary pyridoxine (PX) on the growth of Morris hepatoma no. 7288Ctc was studied. Buffalo strain female rats were fed a diet lacking PX. Pair-fed controls were fed the same diet with PX added. Animals were inoculated with no. 7288Ctc hepatoma cells at 21 days and were sacrificed 16 days later. Host livers and tumors were removed, weights recorded and the activity of tyrosine aminotransferase (TAT; L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was determined in both host liver and hepatoma. The average weight of 30 hepatomas grown in pair-fed control rats was 11.61 +/- 1.5 g while the average weight of the same number of hepatomas grown in animals fed the PX free diet was 4.73 +/- 0.7 g (P less than 0.001). Further TAT specific activity levels were 39% and 32% higher in host livers and tumors from deficient animals, respectively. The results show that availability of dietary pyridoxine stimulates the growth of this hepatoma and, in addition, exercises a type of control over the expression of TAT activity.", "contents": "Effect of pyridoxine on the growth of Morris hepatoma No. 7288Ctc and enzyme activity. The effect(s) of lack of dietary pyridoxine (PX) on the growth of Morris hepatoma no. 7288Ctc was studied. Buffalo strain female rats were fed a diet lacking PX. Pair-fed controls were fed the same diet with PX added. Animals were inoculated with no. 7288Ctc hepatoma cells at 21 days and were sacrificed 16 days later. Host livers and tumors were removed, weights recorded and the activity of tyrosine aminotransferase (TAT; L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was determined in both host liver and hepatoma. The average weight of 30 hepatomas grown in pair-fed control rats was 11.61 +/- 1.5 g while the average weight of the same number of hepatomas grown in animals fed the PX free diet was 4.73 +/- 0.7 g (P less than 0.001). Further TAT specific activity levels were 39% and 32% higher in host livers and tumors from deficient animals, respectively. The results show that availability of dietary pyridoxine stimulates the growth of this hepatoma and, in addition, exercises a type of control over the expression of TAT activity."}
{"id": "PMID:17085", "title": "Expression of hormonally induced tyrosine transaminase in normal, host liver and three Morris hepatomas.", "content": "Cytoplasmic tyrosine transaminase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from normal, host liver and three Morris hepatomas and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Seven enzymatically active forms were detected in normal liver. The presence of growing hepatomas altered significantly the expression of this enzyme. Only one, two and four activity peaks were detected in the host liver of animals with highly (most liver-like), well and poorly (least liver-like) differentiated hepatomas, respectively. Similarly, only one, four and six peaks were detected, respectively, in highly, well and poor differentiated hepatomas.", "contents": "Expression of hormonally induced tyrosine transaminase in normal, host liver and three Morris hepatomas. Cytoplasmic tyrosine transaminase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from normal, host liver and three Morris hepatomas and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Seven enzymatically active forms were detected in normal liver. The presence of growing hepatomas altered significantly the expression of this enzyme. Only one, two and four activity peaks were detected in the host liver of animals with highly (most liver-like), well and poorly (least liver-like) differentiated hepatomas, respectively. Similarly, only one, four and six peaks were detected, respectively, in highly, well and poor differentiated hepatomas."}
{"id": "PMID:17086", "title": "[Allogenic inhibition of the stem hematopoietic cells in the bone marrow of adult mice and in the embryonal liver].", "content": "The maternal effect was shown to influence the degree of allogenic inhibition of stem hemopoietic cells of the embryonic liver and adult bone marrow in CBA and C57Bl/6 mice. The display of allogenic inhibition of stem cells of the embryonic liver and adult bone marrow proved to be similar in C57Bl/6 mice and dissimilar in CBA.", "contents": "[Allogenic inhibition of the stem hematopoietic cells in the bone marrow of adult mice and in the embryonal liver]. The maternal effect was shown to influence the degree of allogenic inhibition of stem hemopoietic cells of the embryonic liver and adult bone marrow in CBA and C57Bl/6 mice. The display of allogenic inhibition of stem cells of the embryonic liver and adult bone marrow proved to be similar in C57Bl/6 mice and dissimilar in CBA."}
{"id": "PMID:17087", "title": "[Effect of syngenic lymphocytes on allogenic inhibition of hematopoietic stem cells of embryonic liver].", "content": "The transplantation of liver from the embryos and newborn C57BL-6 mice to the lethally irradiated hybrids (CBA X C57BL/6) F1resulted in 90% allogenic inhibition of the colony-forming activity of the donor elements. The degree of allogenic inhibition of liver cells of 19 days old embryos and newborn mice may be changed with the help of syngenic lymphocytes of adult mice or delayed transplantation of cells 72 hrs following the irradiation of recipients but these procedures proved to be ineffective with the liver cells of 13 and 16 days old embryos. A suggestion is put forward to the effect that the allogenic inhibition is based on the active reaction of recipient hybrids (CBAXXC57BL/6) F1 to the stem hemopoietic cells of C57BL/6 mice.", "contents": "[Effect of syngenic lymphocytes on allogenic inhibition of hematopoietic stem cells of embryonic liver]. The transplantation of liver from the embryos and newborn C57BL-6 mice to the lethally irradiated hybrids (CBA X C57BL/6) F1resulted in 90% allogenic inhibition of the colony-forming activity of the donor elements. The degree of allogenic inhibition of liver cells of 19 days old embryos and newborn mice may be changed with the help of syngenic lymphocytes of adult mice or delayed transplantation of cells 72 hrs following the irradiation of recipients but these procedures proved to be ineffective with the liver cells of 13 and 16 days old embryos. A suggestion is put forward to the effect that the allogenic inhibition is based on the active reaction of recipient hybrids (CBAXXC57BL/6) F1 to the stem hemopoietic cells of C57BL/6 mice."}
{"id": "PMID:17088", "title": "[NAD+/NADH ratio in the mitochondria of the oocytes and ova of groundling, Misgurnus fossilis (L.)].", "content": "The ratio NAD+/NAD-H was detemined in mitochondria of the loach oocytes and eggs on the basis of concentrations of the glutamate dehydrogenase reaction intermediates. This ratio increases 6 times upon the oocyte maturation. The importance of this ratio in the metabolism of oocyte and embryo is discussed.", "contents": "[NAD+/NADH ratio in the mitochondria of the oocytes and ova of groundling, Misgurnus fossilis (L.)]. The ratio NAD+/NAD-H was detemined in mitochondria of the loach oocytes and eggs on the basis of concentrations of the glutamate dehydrogenase reaction intermediates. This ratio increases 6 times upon the oocyte maturation. The importance of this ratio in the metabolism of oocyte and embryo is discussed."}
{"id": "PMID:17090", "title": "A comprehensive treatment approach to chronic low back pain.", "content": "A comprehensive treatment program for chronic disability related to back disease has been presented. This program has used not only more traditional methods of medical care for the structural disabilities of chronic mechanical back disorders, but has used principles of active patient participation in the improvement process. The patients are educated in the manifestations of pain behavior in the phase II treatment program emphasis on pain sources is downgraded to allow positive reinforcement for healthy behavior to develop. By use of an organized team approach, a significant number of patients can be processed; and an overall reduction in use of alternative medical resources has occurred.", "contents": "A comprehensive treatment approach to chronic low back pain. A comprehensive treatment program for chronic disability related to back disease has been presented. This program has used not only more traditional methods of medical care for the structural disabilities of chronic mechanical back disorders, but has used principles of active patient participation in the improvement process. The patients are educated in the manifestations of pain behavior in the phase II treatment program emphasis on pain sources is downgraded to allow positive reinforcement for healthy behavior to develop. By use of an organized team approach, a significant number of patients can be processed; and an overall reduction in use of alternative medical resources has occurred."}
{"id": "PMID:17092", "title": "Effect of valine on propionate metabolism in control and hyperglycinemic fibroblasts and in rat liver.", "content": "Measurement of methylmalonyl-CoA mutase and propionyl-CoA carboxylase activities in lysates from fibroblasts derived from control, nonketotic hyperglycinemia, propionic acidemia, and both vitamin B12-responsive and -nonresponsive variants of methylmalonic acidemia showed only one abnormality: a 59% decrease in carboxylase activity in the nonketotic hyperglycinemic lysates (P less than 0.01). When fibroblasts from all cell types were grown on valine-supplemented (24 mM) media, mutase activity was generally inhibited. As for carboxylase activity, control lines were inhibited 35% as compared to controls without valine and propionic acidemia activity was undetectable. On the other hand, carboxylase activity in both methylmalonic acidemia variants was increased 40% and nonketotic hyperglycinemia carboxylase activity was increased 80% (P less than 0.01) when grown on valine-supplemented media. Isoleucine could not substitute for valine in producing increased carboxylase activity in these mutants. Glycine cleavage activity in fresh rat liver homogenates (11.1 micronmol/gm protein/90 min) did not vary significantly when 24 mM valine was added to the reaction (9.9 micronmol/mg protein/90 min). Therefore, the hyperglycinemia observed in both ketotic and nonketotic forms is probably not caused by a direct effect of valine on the glycine cleavage reaction. These data suggest that the presence of increased amounts of propionic acid in serum or urine does not necessarily rule out the possibility of nonketotic hyperglycinemia due to the decreased activity of the carboxylase enzyme.", "contents": "Effect of valine on propionate metabolism in control and hyperglycinemic fibroblasts and in rat liver. Measurement of methylmalonyl-CoA mutase and propionyl-CoA carboxylase activities in lysates from fibroblasts derived from control, nonketotic hyperglycinemia, propionic acidemia, and both vitamin B12-responsive and -nonresponsive variants of methylmalonic acidemia showed only one abnormality: a 59% decrease in carboxylase activity in the nonketotic hyperglycinemic lysates (P less than 0.01). When fibroblasts from all cell types were grown on valine-supplemented (24 mM) media, mutase activity was generally inhibited. As for carboxylase activity, control lines were inhibited 35% as compared to controls without valine and propionic acidemia activity was undetectable. On the other hand, carboxylase activity in both methylmalonic acidemia variants was increased 40% and nonketotic hyperglycinemia carboxylase activity was increased 80% (P less than 0.01) when grown on valine-supplemented media. Isoleucine could not substitute for valine in producing increased carboxylase activity in these mutants. Glycine cleavage activity in fresh rat liver homogenates (11.1 micronmol/gm protein/90 min) did not vary significantly when 24 mM valine was added to the reaction (9.9 micronmol/mg protein/90 min). Therefore, the hyperglycinemia observed in both ketotic and nonketotic forms is probably not caused by a direct effect of valine on the glycine cleavage reaction. These data suggest that the presence of increased amounts of propionic acid in serum or urine does not necessarily rule out the possibility of nonketotic hyperglycinemia due to the decreased activity of the carboxylase enzyme."}
{"id": "PMID:17093", "title": "Otitis media in children less than 12 weeks of age.", "content": "Cases of otitis media in infants under 12 weeks of age were reviewed to delineate the frequency, clinical features, and etiologic agents involved. Tympanocentesis was performed in 42 infants, 0 to 5 weeks of age, and in 17, from 6 to 11 weeks of age. The most common symptoms were irritability/lethargy (69%), fever (52%), cough (36%), vomiting (21%), diarrhea (20%), tachypnea (20%), and anorexia (18%). Associated illnesses were present in 33 (54%) of the patients, the most common being pneumonia (9), bronchiolitis (7), meningitis (6), conjunctivitis (4), and omphalitis (4). No peripartum infections or severe perinatal problems were found. Common respiratory pathogens were the predominant etiologic organisms, but coliform organisms were identified in 18% of the infants under 6 weeks of age. Cultures were sterile or grew organisms of questionable pathogenicity (\"nonpathogens\") in 39% of specimens. Since the signs and symptoms of otitis media in children less than 12 weeks of age are nonspecific and frequently associated with other major illnesses, the physician caring for these infants needs to be more aware of this disease and the therapeutic problems it presents.", "contents": "Otitis media in children less than 12 weeks of age. Cases of otitis media in infants under 12 weeks of age were reviewed to delineate the frequency, clinical features, and etiologic agents involved. Tympanocentesis was performed in 42 infants, 0 to 5 weeks of age, and in 17, from 6 to 11 weeks of age. The most common symptoms were irritability/lethargy (69%), fever (52%), cough (36%), vomiting (21%), diarrhea (20%), tachypnea (20%), and anorexia (18%). Associated illnesses were present in 33 (54%) of the patients, the most common being pneumonia (9), bronchiolitis (7), meningitis (6), conjunctivitis (4), and omphalitis (4). No peripartum infections or severe perinatal problems were found. Common respiratory pathogens were the predominant etiologic organisms, but coliform organisms were identified in 18% of the infants under 6 weeks of age. Cultures were sterile or grew organisms of questionable pathogenicity (\"nonpathogens\") in 39% of specimens. Since the signs and symptoms of otitis media in children less than 12 weeks of age are nonspecific and frequently associated with other major illnesses, the physician caring for these infants needs to be more aware of this disease and the therapeutic problems it presents."}
{"id": "PMID:17095", "title": "[Diagnosis of hepatic metastasis by enzymatic assay. Value of gamma-glutamyltranspeptidase].", "content": "Variations in serum enzyme levels were studied in 50 patients suffering from various types of neoplasm, 25 of whom had hepatic metastases. In the absence of any associated hepato-biliary or pancreatic disorder, gamma-glutamyl-transpeptidase would appear to be a reliable test in 96 % of cases. It represents a factor of assessment which merits a place in the prognostic study of all types of neoplasia.", "contents": "[Diagnosis of hepatic metastasis by enzymatic assay. Value of gamma-glutamyltranspeptidase]. Variations in serum enzyme levels were studied in 50 patients suffering from various types of neoplasm, 25 of whom had hepatic metastases. In the absence of any associated hepato-biliary or pancreatic disorder, gamma-glutamyl-transpeptidase would appear to be a reliable test in 96 % of cases. It represents a factor of assessment which merits a place in the prognostic study of all types of neoplasia."}
{"id": "PMID:17096", "title": "Aminoacylation of tRNA Trp from beef liver, yeast and E. coli by beef pancrease tryptophan-tRNA ligase. Stoichiometry of tRNATrp binding.", "content": "The Michaelis constants and the maximum velocities in the aminoacylation reaction of tRNATrp from beef liver, yeast and E. coli by pure beef pancreas tryptophan-tRNA ligase show that this mammalian enzyme recognizes and charges the two eucaryotic tRNAs with the same efficiency. The rate of aminoacylation of the procaryotic tRNATrp by the enzyme is three orders of magnitude lower. The pH optimum of aminoacylation is 8 for both eucaryotic tRNAs. The optimum magnesium concentration is different. The rate is maximum when magnesium concentration is stoichiometric to ATP concentration for tRNATrp from beef liver and 10 mM above ATP concentration for tRNATrp from yeast. The number of binding sites on the enzyme for the two eucaryotic tRNAs has been measured by equilibrium filtration on Sephadex G-100 and found equal to two.", "contents": "Aminoacylation of tRNA Trp from beef liver, yeast and E. coli by beef pancrease tryptophan-tRNA ligase. Stoichiometry of tRNATrp binding. The Michaelis constants and the maximum velocities in the aminoacylation reaction of tRNATrp from beef liver, yeast and E. coli by pure beef pancreas tryptophan-tRNA ligase show that this mammalian enzyme recognizes and charges the two eucaryotic tRNAs with the same efficiency. The rate of aminoacylation of the procaryotic tRNATrp by the enzyme is three orders of magnitude lower. The pH optimum of aminoacylation is 8 for both eucaryotic tRNAs. The optimum magnesium concentration is different. The rate is maximum when magnesium concentration is stoichiometric to ATP concentration for tRNATrp from beef liver and 10 mM above ATP concentration for tRNATrp from yeast. The number of binding sites on the enzyme for the two eucaryotic tRNAs has been measured by equilibrium filtration on Sephadex G-100 and found equal to two."}
{"id": "PMID:17097", "title": "Equimolar addition of oligoribonucleotides with T4 RNA ligase.", "content": "T4 induced RNA ligase will join equimolar concentrations of two oligoribonucleotides, (Ap)3C and p(Up) 5, to form a single product, (Ap)3Cp(Up) 5, in high yield. The presence of the 3' phosphate on p(Up)5 prevents the  oligomer from adding to itself. The pH optimum of the reaction is about 7.5, but less of the undesirable adenylated intermediate, App(Up) 5, forms at pH 8.2. The reaction rate is a linear function of oligomer concentration from 3 micronM to 0.6 mM. The data suggest that T4 RNA ligase will be a useful enzyme for the synthesis of oligomers of defined sequence.", "contents": "Equimolar addition of oligoribonucleotides with T4 RNA ligase. T4 induced RNA ligase will join equimolar concentrations of two oligoribonucleotides, (Ap)3C and p(Up) 5, to form a single product, (Ap)3Cp(Up) 5, in high yield. The presence of the 3' phosphate on p(Up)5 prevents the  oligomer from adding to itself. The pH optimum of the reaction is about 7.5, but less of the undesirable adenylated intermediate, App(Up) 5, forms at pH 8.2. The reaction rate is a linear function of oligomer concentration from 3 micronM to 0.6 mM. The data suggest that T4 RNA ligase will be a useful enzyme for the synthesis of oligomers of defined sequence."}
{"id": "PMID:17098", "title": "Circular dichroism study of polyriboxanthylic acid.", "content": "We report in the present paper the circular dichroism spectra of poly(X) at different pH and temperature values. The spectra are characteristic of three stable forms of poly(x) in the pH range of protonation of xanthosine. An electrostatic barrier is proposed to account for the hysteresis and metastability observed in a certain pH range. Some results on oligo(X) at basic pH are also presented. Poly(X) at basic pH is investigated also by hydrodynamic techniques.", "contents": "Circular dichroism study of polyriboxanthylic acid. We report in the present paper the circular dichroism spectra of poly(X) at different pH and temperature values. The spectra are characteristic of three stable forms of poly(x) in the pH range of protonation of xanthosine. An electrostatic barrier is proposed to account for the hysteresis and metastability observed in a certain pH range. Some results on oligo(X) at basic pH are also presented. Poly(X) at basic pH is investigated also by hydrodynamic techniques."}
{"id": "PMID:17099", "title": "Polyamine induced aggregation of DNA.", "content": "Polyamine induced aggregation of various DNAs has been studied under conditions usually employed in many enzymatic assays where DNA is one of the substrates. Spermine was by far the most efficient polyamine in causing aggregation followed by spermidine and cadaverine. All double-stranded and naturally occurring single-stranded DNAs were found to aggregate. No aggregation of single-stranded homodeoxypolymers could be detected under the same conditions. The concentration of polyamine at which the aggregation commenced was found to be a linear function of the DNA concentration. The slope of the curves depended on the nature of the polyamine, DNA the concentration of Mg++ and the ionic strength.", "contents": "Polyamine induced aggregation of DNA. Polyamine induced aggregation of various DNAs has been studied under conditions usually employed in many enzymatic assays where DNA is one of the substrates. Spermine was by far the most efficient polyamine in causing aggregation followed by spermidine and cadaverine. All double-stranded and naturally occurring single-stranded DNAs were found to aggregate. No aggregation of single-stranded homodeoxypolymers could be detected under the same conditions. The concentration of polyamine at which the aggregation commenced was found to be a linear function of the DNA concentration. The slope of the curves depended on the nature of the polyamine, DNA the concentration of Mg++ and the ionic strength."}
{"id": "PMID:17100", "title": "Glycosyl conformational and inductive effects on the acid catalysed hydrolysis of purine nucleosides.", "content": "The log kobs vs. pH profiles were determined in the intermediate acidity region for the glycosyl hydrolysis of guanosine and its 8-amino, 8-monomethylamino, 8-dimethylamino and 8-bromo derivatives. The decreased rate of the 8-amino and enhanced rate of the 8-bromo compound compared to guanosine support an A type mechanism: base protonation followed by glycosyl bond cleavage. All three 8-amino guanosines exhibited log kobs - pH profiles clearly showing that both mono and di-base protonated nucleosides undergo hydrolysis. The 700 fold rate acceleration of 8-N(CH3)-guanosine compared to 8-NHCH3-guanosine and the 110 fold rate acceleration of 8-N(CH3)2-adenosine compared to 8-NHCH3-adenosine could be unequivocally attributed to the fixed syn glycosyl conformation of both 8-dimethylamino compounds and relief of steric compression upon hydrolysis in these molecules. The lack of anomerization of all substrates during the course of the reaction supports an A rather than a Schiff-base mechanism.", "contents": "Glycosyl conformational and inductive effects on the acid catalysed hydrolysis of purine nucleosides. The log kobs vs. pH profiles were determined in the intermediate acidity region for the glycosyl hydrolysis of guanosine and its 8-amino, 8-monomethylamino, 8-dimethylamino and 8-bromo derivatives. The decreased rate of the 8-amino and enhanced rate of the 8-bromo compound compared to guanosine support an A type mechanism: base protonation followed by glycosyl bond cleavage. All three 8-amino guanosines exhibited log kobs - pH profiles clearly showing that both mono and di-base protonated nucleosides undergo hydrolysis. The 700 fold rate acceleration of 8-N(CH3)-guanosine compared to 8-NHCH3-guanosine and the 110 fold rate acceleration of 8-N(CH3)2-adenosine compared to 8-NHCH3-adenosine could be unequivocally attributed to the fixed syn glycosyl conformation of both 8-dimethylamino compounds and relief of steric compression upon hydrolysis in these molecules. The lack of anomerization of all substrates during the course of the reaction supports an A rather than a Schiff-base mechanism."}
{"id": "PMID:17101", "title": "Isolation and characterization of N6-succinyladenosine from human urine.", "content": "From the urines of colon carcinoma patients and normal  subjects we have isolated a nucleoside in which an amino group of aspartic acid is attached to the six position of purine ribonucleoside. The structure, N6-succinyladenosine, N-(9-B-D-ribofuranosylpurin-6-yl)aspartic acid was assigned on the basis of spectral data, chemical degradation, and by synthesis. The ultraviolet and mass spectra, chromatographic and electrophoretic mobilities, and the chemical properties of the naturally occurring nucleoside were identical to those of the synthetic N6-succinyladenosine. In contrast to the methylated and hypermodified nucleosides which are products of RNA catabolism, this urinary nucleoside appears to be derived from adenylosuccinic acid, a key intermediate required in the biosynthesis of ubiquitous, natural purine nucleotide adenosine-5'-monophosphate (AMP).", "contents": "Isolation and characterization of N6-succinyladenosine from human urine. From the urines of colon carcinoma patients and normal  subjects we have isolated a nucleoside in which an amino group of aspartic acid is attached to the six position of purine ribonucleoside. The structure, N6-succinyladenosine, N-(9-B-D-ribofuranosylpurin-6-yl)aspartic acid was assigned on the basis of spectral data, chemical degradation, and by synthesis. The ultraviolet and mass spectra, chromatographic and electrophoretic mobilities, and the chemical properties of the naturally occurring nucleoside were identical to those of the synthetic N6-succinyladenosine. In contrast to the methylated and hypermodified nucleosides which are products of RNA catabolism, this urinary nucleoside appears to be derived from adenylosuccinic acid, a key intermediate required in the biosynthesis of ubiquitous, natural purine nucleotide adenosine-5'-monophosphate (AMP)."}
{"id": "PMID:17102", "title": "Polynucleotides. XLVI. 1 Synthesis and properties of poly (2'-amino-2'-deoxyadenylic acid).", "content": "Poly (2'-amino-2'-deoxyadenylic acid)  [poly (Aa)] was prepared from chemically synthesized 2'-amino-2'-deoxy-ADP by the catalysis of polynucleotide phosphorylase. Poly (Aa) showed a similar UV absorption spectra to poly (A), but quite different CD spectra at pH 7.0 and 5.7. At the former pH it showed a single negative Cotton band and at the latter a curve with a large splitting of bands. Acid titration of poly (Aa) suggested protonated form below pH 7.0. Temperature absorption profiles and their dependency on sodium ion concentration suggested an ordered structure for poly (Aa) which is stabilized by stacking of bases and intrastrand interaction between 2'-amino and internucleotidic phosphate groups. Poly (Aa) forms a 1:2 complex with poly (U) at neutrality and its Tm was 45 degrees in the presence of 0.15M sodium ion.", "contents": "Polynucleotides. XLVI. 1 Synthesis and properties of poly (2'-amino-2'-deoxyadenylic acid). Poly (2'-amino-2'-deoxyadenylic acid)  [poly (Aa)] was prepared from chemically synthesized 2'-amino-2'-deoxy-ADP by the catalysis of polynucleotide phosphorylase. Poly (Aa) showed a similar UV absorption spectra to poly (A), but quite different CD spectra at pH 7.0 and 5.7. At the former pH it showed a single negative Cotton band and at the latter a curve with a large splitting of bands. Acid titration of poly (Aa) suggested protonated form below pH 7.0. Temperature absorption profiles and their dependency on sodium ion concentration suggested an ordered structure for poly (Aa) which is stabilized by stacking of bases and intrastrand interaction between 2'-amino and internucleotidic phosphate groups. Poly (Aa) forms a 1:2 complex with poly (U) at neutrality and its Tm was 45 degrees in the presence of 0.15M sodium ion."}
{"id": "PMID:17103", "title": "The ANA and research in nursing.", "content": "Research activities which always have been part of the American Nurses' Association program have increased greatly in the last 15 years. Among ANA's significant contributions to nursing research have been sponsoring nine nursing research conferences (1965-1973) and establishing the ANA Commission on Nursing Research and Council of Nurse Researchers.", "contents": "The ANA and research in nursing. Research activities which always have been part of the American Nurses' Association program have increased greatly in the last 15 years. Among ANA's significant contributions to nursing research have been sponsoring nine nursing research conferences (1965-1973) and establishing the ANA Commission on Nursing Research and Council of Nurse Researchers."}
{"id": "PMID:17108", "title": "[Study of the conditions maintaining the synthesis of alpha-amylase by Bacillus species].", "content": "The effect of temperature and different carbon sources on the growth of Bacillus species and the synthesis of alpha-amylase was studied. The temperature of 40 degrees proved to be optimal for those processes. Starch was found to be the best carbon source. The maximum accumulation of the enzyme was seen by the 40th hour of growth.", "contents": "[Study of the conditions maintaining the synthesis of alpha-amylase by Bacillus species]. The effect of temperature and different carbon sources on the growth of Bacillus species and the synthesis of alpha-amylase was studied. The temperature of 40 degrees proved to be optimal for those processes. Starch was found to be the best carbon source. The maximum accumulation of the enzyme was seen by the 40th hour of growth."}
{"id": "PMID:17109", "title": "[Phospholipase of Bacillus cereus].", "content": "Phospholipase activity of 10 strains of Bacillus cereus was studied. The most active strain of Bac. cereus--phospholipase producer was selected. A cultivation mixture of Bac. cereus optimal for the phospholipase synthesis was found to include peptone, yeast extract, glucose, NaCl and Na2HPO4. Proper conditions for the synthesis of phospholipase in flasks, 20 l and 250 l fermenters were tested. The maximum increase of the phospholipase activity occurred by the 5-9th hour of microbial growth at pH 6.0-8.0. Further cultivation, foaming, strong aeration, pH increase (over 8.0) reduced the accumulated activity. By fractionation with (NH4)2SO4, ethanol precipitation, protamine sulphate treatment with subsequent Sephadex G-100 gel filtration phospholipase (EC 3.1.4.3) was purified 300-fold from the culture liquid of Bac. cereus str. 504. The preparation was examined electrophoretically in 7% polyacrylamide gel at alkaline pH. The effect of metal salts and EDTA on phospholipase activity was studied. Thermostability, substrate specificity and pH optimum of purified phospholipase were investigated.", "contents": "[Phospholipase of Bacillus cereus]. Phospholipase activity of 10 strains of Bacillus cereus was studied. The most active strain of Bac. cereus--phospholipase producer was selected. A cultivation mixture of Bac. cereus optimal for the phospholipase synthesis was found to include peptone, yeast extract, glucose, NaCl and Na2HPO4. Proper conditions for the synthesis of phospholipase in flasks, 20 l and 250 l fermenters were tested. The maximum increase of the phospholipase activity occurred by the 5-9th hour of microbial growth at pH 6.0-8.0. Further cultivation, foaming, strong aeration, pH increase (over 8.0) reduced the accumulated activity. By fractionation with (NH4)2SO4, ethanol precipitation, protamine sulphate treatment with subsequent Sephadex G-100 gel filtration phospholipase (EC 3.1.4.3) was purified 300-fold from the culture liquid of Bac. cereus str. 504. The preparation was examined electrophoretically in 7% polyacrylamide gel at alkaline pH. The effect of metal salts and EDTA on phospholipase activity was studied. Thermostability, substrate specificity and pH optimum of purified phospholipase were investigated."}
{"id": "PMID:17110", "title": "[Comparative study of the properties of lipase of microbial origin].", "content": "A comparative study of properties of lipases of microbial origin has shown that the pH optimum of the enzymes from Geotrichum asteroides and Penicillium sp. is at pH 7.5 and 5.0, respectively. Lipase from Geotrichum asteroides appears more resistant to high temperatures and pH changes than the enzyme from Penicillium sp. Both enzymes split selectively vegetable oils, especially cotton and sunflower oils. Na cholate and deoxycholate at a concentration of 0.05-0.4% act as hydrolysis activators, particularly with respect to Geotrichum lipase. Na dehydrocholate does not show this effect.", "contents": "[Comparative study of the properties of lipase of microbial origin]. A comparative study of properties of lipases of microbial origin has shown that the pH optimum of the enzymes from Geotrichum asteroides and Penicillium sp. is at pH 7.5 and 5.0, respectively. Lipase from Geotrichum asteroides appears more resistant to high temperatures and pH changes than the enzyme from Penicillium sp. Both enzymes split selectively vegetable oils, especially cotton and sunflower oils. Na cholate and deoxycholate at a concentration of 0.05-0.4% act as hydrolysis activators, particularly with respect to Geotrichum lipase. Na dehydrocholate does not show this effect."}
{"id": "PMID:17111", "title": "[Method of determination of the activity of glycerol dehydrogenase in the submerged culture of Acetobacter suboxydans].", "content": "The paper presents a method for assaying activity of glycerol dehydrogenase activity in the submerged culture of Acetobacter suboxydans. The effect of substrate concentration, content of the submerged culture in the reaction mixture and pH value on the rate of enzymic oxidation of glycerol to dihygrooxyacetone by A. suboxydans has been studied.", "contents": "[Method of determination of the activity of glycerol dehydrogenase in the submerged culture of Acetobacter suboxydans]. The paper presents a method for assaying activity of glycerol dehydrogenase activity in the submerged culture of Acetobacter suboxydans. The effect of substrate concentration, content of the submerged culture in the reaction mixture and pH value on the rate of enzymic oxidation of glycerol to dihygrooxyacetone by A. suboxydans has been studied."}
{"id": "PMID:17115", "title": "A DNA nicking-closing enzyme encapsidated in vaccinia virus: partial purification and properties.", "content": "Vaccinia virus cores contain an activity which is able to relax both left-and right-handed superhelical DNA. This virus-specific nicking closing enzyme has been highly purified and differs from the corresponding host enzyme in salt optimum, in sedimentation coefficient, and in polypeptide composition as determined on sodium dodecyl sulfate/polyacrylamide gels. The enzyme is probably newly synthesized after the cessation of host protein synthesis which follows virus infection. The most highly purified preparation contains two polypeptides, one of molecular weight 24,000 and the other 35,000. The former polypeptide is a major constituent of the virus (7% of total protein by weight), whereas the latter is present in a much smaller amount (0.2%). Chromatography with denatured DNA-cellulose reveals that the activity is predominately associated with those fractions enriched in the polypeptide of greater molecular weight.", "contents": "A DNA nicking-closing enzyme encapsidated in vaccinia virus: partial purification and properties. Vaccinia virus cores contain an activity which is able to relax both left-and right-handed superhelical DNA. This virus-specific nicking closing enzyme has been highly purified and differs from the corresponding host enzyme in salt optimum, in sedimentation coefficient, and in polypeptide composition as determined on sodium dodecyl sulfate/polyacrylamide gels. The enzyme is probably newly synthesized after the cessation of host protein synthesis which follows virus infection. The most highly purified preparation contains two polypeptides, one of molecular weight 24,000 and the other 35,000. The former polypeptide is a major constituent of the virus (7% of total protein by weight), whereas the latter is present in a much smaller amount (0.2%). Chromatography with denatured DNA-cellulose reveals that the activity is predominately associated with those fractions enriched in the polypeptide of greater molecular weight."}
{"id": "PMID:17113", "title": "[Desugarization of egg white by microorganisms].", "content": "Glucose was eliminated from egg whites, using microorganisms, to prevent melanoidin formation which may damage the product. Desugarization was achieved by means of Acetobacter xylinum, Streptococcus lactis, Propionibacterium shermanii, Pr. petersonii and propionicacid cocci. Optimal conditions of desugarization were found, depending on the physiological characteristics of the above microorganisms. Propionibacterium shermanii may be well used to ferment a liquid egg white. These bacteria have no proteolytic properties and make no use of the egg white. They enrich the egg white with vitamin B12 and propionate, a preserving agent, during fermentation.", "contents": "[Desugarization of egg white by microorganisms]. Glucose was eliminated from egg whites, using microorganisms, to prevent melanoidin formation which may damage the product. Desugarization was achieved by means of Acetobacter xylinum, Streptococcus lactis, Propionibacterium shermanii, Pr. petersonii and propionicacid cocci. Optimal conditions of desugarization were found, depending on the physiological characteristics of the above microorganisms. Propionibacterium shermanii may be well used to ferment a liquid egg white. These bacteria have no proteolytic properties and make no use of the egg white. They enrich the egg white with vitamin B12 and propionate, a preserving agent, during fermentation."}
{"id": "PMID:17116", "title": "H+/ATP ratio during ATP hydrolysis by mitochondria: modification of the chemiosmotic theory.", "content": "The stoichiometry of H+ ejection by mitochondria during hydrolysis of a small pulse of ATP (the H+/ATP ratio) has been reexamined in the light of our recent observation that the stoichiometry of H+ ejection during mitochondrial electron transport (the H+/site ratio) was previously underestimated. We show that earlier estimates of the H+/ATP ratio in intact mitochondria were based upon an invalid correction for scaler H+ production and describe a modified method for determination of this ratio which utilizes mersalyl or N-ethylmaleimide to prevent complicating transmembrane movements of phosphate and H+. This method gives a value for the H+/ATP ratio of 2.0 without the need for questionable corrections, compared with a value of 3.0 for the H+/site ratio also obtained by pulse methods. A modified version of the chemiosmotic theory is presented, in which 3 H+ are ejected per pair of electrons traversing each energy-conserving site of the respiratory chain. Of these, 2 H+ return to the matrix through the ATPase to form ATP from ADP and phosphate, and 1 H+ returns through the combined action of the phosphate and adenine nucleotide exchange carriers of the inner membrane to allow the energy-requiring influx of Pi and ADP3- and efflux of ATP4-. Thus, up to one-third of the energy input into synthesis of extramitochondrial ATP may be required for transport work. Since other methods suggest that the H+/site significantly exceeds 3.0, an alternative possibility is that 4 h+ are ejected per site, followed by return of 3 H+ through the ATPase and 1 H+ through the operation of the proton-coupled membrane transport systems.", "contents": "H+/ATP ratio during ATP hydrolysis by mitochondria: modification of the chemiosmotic theory. The stoichiometry of H+ ejection by mitochondria during hydrolysis of a small pulse of ATP (the H+/ATP ratio) has been reexamined in the light of our recent observation that the stoichiometry of H+ ejection during mitochondrial electron transport (the H+/site ratio) was previously underestimated. We show that earlier estimates of the H+/ATP ratio in intact mitochondria were based upon an invalid correction for scaler H+ production and describe a modified method for determination of this ratio which utilizes mersalyl or N-ethylmaleimide to prevent complicating transmembrane movements of phosphate and H+. This method gives a value for the H+/ATP ratio of 2.0 without the need for questionable corrections, compared with a value of 3.0 for the H+/site ratio also obtained by pulse methods. A modified version of the chemiosmotic theory is presented, in which 3 H+ are ejected per pair of electrons traversing each energy-conserving site of the respiratory chain. Of these, 2 H+ return to the matrix through the ATPase to form ATP from ADP and phosphate, and 1 H+ returns through the combined action of the phosphate and adenine nucleotide exchange carriers of the inner membrane to allow the energy-requiring influx of Pi and ADP3- and efflux of ATP4-. Thus, up to one-third of the energy input into synthesis of extramitochondrial ATP may be required for transport work. Since other methods suggest that the H+/site significantly exceeds 3.0, an alternative possibility is that 4 h+ are ejected per site, followed by return of 3 H+ through the ATPase and 1 H+ through the operation of the proton-coupled membrane transport systems."}
{"id": "PMID:17117", "title": "9S binding protein for androgens and progesterone.", "content": "A steroid binding protein fraction with a sedimentation coefficient of approximately 9 S (molecular weight approximately equal to 200,000) has been identified in 105,000 X g supernatants of several androgen-responsive organs. Highest concentrations were found in epididymis and testis, but small amounts were detected in prostate, seminal vesicle, kidney, submandibular gland, and lung. The 9S protein binds [3H]dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and [3H]progesterone (4-pregnene-3,20-dione) with equilibrium binding constants of approximately 10(5) M-1 and 10(6) M-1, respectively. The concentration of 9S binding sites in epididymis is approximately 10(-11) mol/mg of supernatant protein, which is at least 10(5) times greater than the concentration of androgen receptor. 9S binding protein appears to be a nonsecretory, intracellular protein and has properties different from the andorgen receptor. It is unretarded on DEAE-Sephadex chromatography at pH 8.0, and its sedimentation rate on sucrose gradients is not altered at high ionic strength (0.4 M KCl). Like the androgen receptor, its binding activity, which is maximal between pH 7 and 9.5, is heat labile, decreased by sulfhydryl reagents, and enhanced by 2-mercaptoethanol. It is suggested that because of its high concentration and low affinity, 9S binding protein may function in the intracellular accumulation of compartmentalization of androgens or progesterone.", "contents": "9S binding protein for androgens and progesterone. A steroid binding protein fraction with a sedimentation coefficient of approximately 9 S (molecular weight approximately equal to 200,000) has been identified in 105,000 X g supernatants of several androgen-responsive organs. Highest concentrations were found in epididymis and testis, but small amounts were detected in prostate, seminal vesicle, kidney, submandibular gland, and lung. The 9S protein binds [3H]dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and [3H]progesterone (4-pregnene-3,20-dione) with equilibrium binding constants of approximately 10(5) M-1 and 10(6) M-1, respectively. The concentration of 9S binding sites in epididymis is approximately 10(-11) mol/mg of supernatant protein, which is at least 10(5) times greater than the concentration of androgen receptor. 9S binding protein appears to be a nonsecretory, intracellular protein and has properties different from the andorgen receptor. It is unretarded on DEAE-Sephadex chromatography at pH 8.0, and its sedimentation rate on sucrose gradients is not altered at high ionic strength (0.4 M KCl). Like the androgen receptor, its binding activity, which is maximal between pH 7 and 9.5, is heat labile, decreased by sulfhydryl reagents, and enhanced by 2-mercaptoethanol. It is suggested that because of its high concentration and low affinity, 9S binding protein may function in the intracellular accumulation of compartmentalization of androgens or progesterone."}
{"id": "PMID:17114", "title": "[Properties of a preparation of lytic enzymes from a culture of Bacillus subtilis].", "content": "The effect of pH, temperature, various salts and other compounds on the activity of the preparation of lytic enzymes from the culture of Bacillus subtilis (lyzosubtilin) was investigated. The preparation was shown to be active in neutral solutions of low ionic strength at 30-50 degrees C. The salts of magnesium, manganese, copper, zinc, lead, mercury, aluminium and iron as well as Tris-buffer and Triton X-100 inhibited lyzosubtilin whereas lactic acid activated it. At 30 degrees C the preparation was stable within the pH range of 5 to 10. Its incubation for 60 min at 60 degrees C resulted in the loss of 50% activity. Lyzosubtilin lyzed cells of gram-positive and gram-negative bacteria, yeast and fungi.", "contents": "[Properties of a preparation of lytic enzymes from a culture of Bacillus subtilis]. The effect of pH, temperature, various salts and other compounds on the activity of the preparation of lytic enzymes from the culture of Bacillus subtilis (lyzosubtilin) was investigated. The preparation was shown to be active in neutral solutions of low ionic strength at 30-50 degrees C. The salts of magnesium, manganese, copper, zinc, lead, mercury, aluminium and iron as well as Tris-buffer and Triton X-100 inhibited lyzosubtilin whereas lactic acid activated it. At 30 degrees C the preparation was stable within the pH range of 5 to 10. Its incubation for 60 min at 60 degrees C resulted in the loss of 50% activity. Lyzosubtilin lyzed cells of gram-positive and gram-negative bacteria, yeast and fungi."}
{"id": "PMID:17118", "title": "Solid-like character of virus solutions.", "content": "The solid-like behavior of turnip yellow mosaic virus solutions following the extrusion of viral RNA in alkali was observed with a torsion-fiber balance developed for the purpose. This method provided a direct measurement of the yield stresses required to break or liquefy these solutions. The yield stresses were found to increase and to be less time dependent with increasing concentrations of the virus and they were maximal at room temperatures. If the virus had been damaged, as by freeze-thaw, little or no solid-like behavior could be demonstrated. Purified viral capsids, with or without added RNA, were also inactive. The values for the yield stresses were of the same order as the value reported previously with the use of a magnetic suspension viscometer; hence, the apparent coherency appears unrelated to the magnetic fields generated by the latter instrument. These solutions behaved as typical liquids after the required stress was applied [about 0.005 to 0.17 dyne cm-2 (0.05 to 1.7 micronN cm-2)], these forces being smaller than those usually conferred by ordinary handling.", "contents": "Solid-like character of virus solutions. The solid-like behavior of turnip yellow mosaic virus solutions following the extrusion of viral RNA in alkali was observed with a torsion-fiber balance developed for the purpose. This method provided a direct measurement of the yield stresses required to break or liquefy these solutions. The yield stresses were found to increase and to be less time dependent with increasing concentrations of the virus and they were maximal at room temperatures. If the virus had been damaged, as by freeze-thaw, little or no solid-like behavior could be demonstrated. Purified viral capsids, with or without added RNA, were also inactive. The values for the yield stresses were of the same order as the value reported previously with the use of a magnetic suspension viscometer; hence, the apparent coherency appears unrelated to the magnetic fields generated by the latter instrument. These solutions behaved as typical liquids after the required stress was applied [about 0.005 to 0.17 dyne cm-2 (0.05 to 1.7 micronN cm-2)], these forces being smaller than those usually conferred by ordinary handling."}
{"id": "PMID:17119", "title": "Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells.", "content": "A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the beta-adrenergic agonist terbutaline and inhibitors of cyclic nucleotide phosphodiesterase. In contrast to the situation in the wild-type clone, synthesis of adenosine 3':5'-monophosphate (cyclic AMP) is not stimulated by beta-adrenergic agonists or by prostaglandin E1 either in intact variant cells or in membrane preparations of such clones. However, basal and NaF-stimulated activities of adenylate cyclase [ATP pyrophosphate-lyase (cyclizine), EC 4.6.1.1] are normal, enzyme activity is stimulated by guanyl-5'-yl imidodiphosphate [Gpp(NH)p], and intact cells accumulate cyclic AMP when exposed to cholera toxin. Furthermore, variant cell membranes possess ligand-binding activity consistent with the conclusion that a normal or an excessive number of beta-adrenergic receptors is present. Thus, interaction between the hormone-binding and the catalytic moieties of the adenylate cyclase system is lost. This variant phenotype, designated as uncoupled (UNC), has been stable for more than 100 generations without exposure to the drugs used for selection. Such cells should be useful for the elucidation of methanisms of transmission of information from hormone receptors to adenylate cyclase.", "contents": "Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells. A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the beta-adrenergic agonist terbutaline and inhibitors of cyclic nucleotide phosphodiesterase. In contrast to the situation in the wild-type clone, synthesis of adenosine 3':5'-monophosphate (cyclic AMP) is not stimulated by beta-adrenergic agonists or by prostaglandin E1 either in intact variant cells or in membrane preparations of such clones. However, basal and NaF-stimulated activities of adenylate cyclase [ATP pyrophosphate-lyase (cyclizine), EC 4.6.1.1] are normal, enzyme activity is stimulated by guanyl-5'-yl imidodiphosphate [Gpp(NH)p], and intact cells accumulate cyclic AMP when exposed to cholera toxin. Furthermore, variant cell membranes possess ligand-binding activity consistent with the conclusion that a normal or an excessive number of beta-adrenergic receptors is present. Thus, interaction between the hormone-binding and the catalytic moieties of the adenylate cyclase system is lost. This variant phenotype, designated as uncoupled (UNC), has been stable for more than 100 generations without exposure to the drugs used for selection. Such cells should be useful for the elucidation of methanisms of transmission of information from hormone receptors to adenylate cyclase."}
{"id": "PMID:17120", "title": "A defined minimal medium for axenic strains of Dictyostelium discoideum.", "content": "A defined, minimal medium for the cellular slime mold Dictyostelium discoideum is reported.", "contents": "A defined minimal medium for axenic strains of Dictyostelium discoideum. A defined, minimal medium for the cellular slime mold Dictyostelium discoideum is reported."}
{"id": "PMID:17133", "title": "[Migrating and recurrent superficial phlebitis and Takayasu's disease (apropos of a case)].", "content": "This case of recurrent migratory superficial phlebitis is reported because of the highly unusual nature of the lesion observed. The picture was dominated by periphlebitis with inflammatory granuloma, giant cells and elastophagia. When the condition had been present for sixteen months, an aortic arch syndrome developed in an inflammatory context. In this light, various auto-immunological etiologies were considered, among them Takayashu's arteritis of which, in the author's opinion, this would be the first case to be combined with venopathy.", "contents": "[Migrating and recurrent superficial phlebitis and Takayasu's disease (apropos of a case)]. This case of recurrent migratory superficial phlebitis is reported because of the highly unusual nature of the lesion observed. The picture was dominated by periphlebitis with inflammatory granuloma, giant cells and elastophagia. When the condition had been present for sixteen months, an aortic arch syndrome developed in an inflammatory context. In this light, various auto-immunological etiologies were considered, among them Takayashu's arteritis of which, in the author's opinion, this would be the first case to be combined with venopathy."}
{"id": "PMID:17140", "title": "Cryptorchism.", "content": "Our results from 121 patients as well as data from the literature prove that fertility rates after treatment of uni- or bilateral cryptorchism remain unsatisfactory. There is no statistically significant difference in fertility between a group of patients treated with human-chorionic-gonadotrophin and another group treated by orchidopexy after unsuccessful hormonal therapy. On the other hand, late results in unilateral cryptorchism are to a statistically significant extent better than in bilateral cryptorchism (46/29%). According to our histological findings in maldescended testicles, early treatment (before the age of 3 years) is advocated.", "contents": "Cryptorchism. Our results from 121 patients as well as data from the literature prove that fertility rates after treatment of uni- or bilateral cryptorchism remain unsatisfactory. There is no statistically significant difference in fertility between a group of patients treated with human-chorionic-gonadotrophin and another group treated by orchidopexy after unsuccessful hormonal therapy. On the other hand, late results in unilateral cryptorchism are to a statistically significant extent better than in bilateral cryptorchism (46/29%). According to our histological findings in maldescended testicles, early treatment (before the age of 3 years) is advocated."}
{"id": "PMID:17141", "title": "Long-term results of undescended testicle operative treatment.", "content": "Men affected with unilateral and bilateral undescended testicles have been examined 10 to 20 years after orchidopexy. The examined patients were divided into groups of individuals operated before and after the 8th year of life. Fertility, structure of the genitals, somatotype, psychosexual behavior, and plasma testosterone levels were tested. It was found that a significant number of cryptorchid patients was infertile, especially the bilateral ones. Abnormalities in the structure of the genitals, somatotype, and in some cases psychosexual behavior disorders as well as plasma testoterone levels lower than normal, have also been found.", "contents": "Long-term results of undescended testicle operative treatment. Men affected with unilateral and bilateral undescended testicles have been examined 10 to 20 years after orchidopexy. The examined patients were divided into groups of individuals operated before and after the 8th year of life. Fertility, structure of the genitals, somatotype, psychosexual behavior, and plasma testosterone levels were tested. It was found that a significant number of cryptorchid patients was infertile, especially the bilateral ones. Abnormalities in the structure of the genitals, somatotype, and in some cases psychosexual behavior disorders as well as plasma testoterone levels lower than normal, have also been found."}
{"id": "PMID:17142", "title": "The vasoconstrictive effect of dopamine in the isolated, perfused rat kidney after catecholamine depletion.", "content": "In the isolated, perfused kidney of untreated and catcholamine-depleted rats (by 6-hydroxydopamine and reserpine), dopamine (DA) caused a dose-dependent increase in vascular resistance which could be prevented by prior blockade of the alpha-adreno-receptors. The DA-induced vasoconstriction thus appears to be due to a direct stimulation of alpha-receptors in the kidney rather than an indirect sympathomimetic effect through release of noradrena-line from local adrenergic nerve terminals. The effectiveness of the chemical sympathectomy accomplished with 6-hydroxydopamine and reserpine was evaluated by chemical; histochemical and electron microscopical methods.", "contents": "The vasoconstrictive effect of dopamine in the isolated, perfused rat kidney after catecholamine depletion. In the isolated, perfused kidney of untreated and catcholamine-depleted rats (by 6-hydroxydopamine and reserpine), dopamine (DA) caused a dose-dependent increase in vascular resistance which could be prevented by prior blockade of the alpha-adreno-receptors. The DA-induced vasoconstriction thus appears to be due to a direct stimulation of alpha-receptors in the kidney rather than an indirect sympathomimetic effect through release of noradrena-line from local adrenergic nerve terminals. The effectiveness of the chemical sympathectomy accomplished with 6-hydroxydopamine and reserpine was evaluated by chemical; histochemical and electron microscopical methods."}
{"id": "PMID:17144", "title": "Role of Pco2 oscillations and chemoreceptors in ventilatory response to inhaled and infused CO2.", "content": "We have previously shown in the anaesthetized rabbit that the ventilatory response to an increase in Paco2 is greater if that increase is produced by intravenous infusion of hypercapnic blood than by inhalation of CO2 (Linton et al., 1976). The present set of experiments was designed to investigate the reason for this. It was found that the difference in ventilatory response observed in the intact rabbit was abolished by cutting the carotid sinus nerves or by eliminating the pH/Paco2 oscillations in the carotid blood flow. It is concluded that the normally greater ventilatory response to intravenous infusion of hypercapnic blood compared with inhalation of CO2 is due to a respiratory signal derived from Paco2 oscillations and carried in the carotid sinus nerves.", "contents": "Role of Pco2 oscillations and chemoreceptors in ventilatory response to inhaled and infused CO2. We have previously shown in the anaesthetized rabbit that the ventilatory response to an increase in Paco2 is greater if that increase is produced by intravenous infusion of hypercapnic blood than by inhalation of CO2 (Linton et al., 1976). The present set of experiments was designed to investigate the reason for this. It was found that the difference in ventilatory response observed in the intact rabbit was abolished by cutting the carotid sinus nerves or by eliminating the pH/Paco2 oscillations in the carotid blood flow. It is concluded that the normally greater ventilatory response to intravenous infusion of hypercapnic blood compared with inhalation of CO2 is due to a respiratory signal derived from Paco2 oscillations and carried in the carotid sinus nerves."}
{"id": "PMID:17152", "title": "Microflora in the healthy gingival sulcus in man.", "content": "The roll tube culture technique was utilized to examine quantitatively and qualitatively the predominant cultivable microflora inhabiting the clinically healthy gingival sulcus. Seven periodontists aged 32-54 years were included in the study. From a total of 350 isolates, 85 (24.3%) were obligate anaerobes, 53 (15.0%) were Gram negative, and 197 (56.3%) were categorized as rods. Actinomycetes predominated in three samples. Four samples were dominated by Streptococcus species. The flora as revealed in the present study comprised a markedly lower proportion of Gram-negative organisms than that found at the base of deep periodontal pockets.", "contents": "Microflora in the healthy gingival sulcus in man. The roll tube culture technique was utilized to examine quantitatively and qualitatively the predominant cultivable microflora inhabiting the clinically healthy gingival sulcus. Seven periodontists aged 32-54 years were included in the study. From a total of 350 isolates, 85 (24.3%) were obligate anaerobes, 53 (15.0%) were Gram negative, and 197 (56.3%) were categorized as rods. Actinomycetes predominated in three samples. Four samples were dominated by Streptococcus species. The flora as revealed in the present study comprised a markedly lower proportion of Gram-negative organisms than that found at the base of deep periodontal pockets."}
{"id": "PMID:17153", "title": "Plasma secretin concentration in anaesthetized pigs after intraduodenal glucose, fat, aminoacids, or meals with various pH.", "content": "The concentration of immunoreactive secretin in portal blood and the secretion from the exocrine pancreas were measured during intraduodenal infusion of isotonic or hypertonic saline, isotonic or hypertonic glucose, aminoacids, fat emulsion, or 0.1 mol X 1(-1) hydrochloric acid in 7 anaesthetized pigs. None of these substances, except hydrochloric acid, had any effect on plasma secretin concentration and pancreatic flow rate and bicarbonate output. Plasma secretin concentration rose significantly from 5.6 +/- 2.7 pmol X 1(-1) (mean +/- S.E.M.) to a peak value of 201.2 +/- 80.5 pmol X 1(-1) 15 min after infusion of hydrochloric acid. Pancreatic flow rate and bicarbonate output increased from 0.51 +/- 0.19 ml X h-1 (mean +/- S.E.M.) to 9.85 +/- 2.33 ml X h-1 and from 52 +/- 11 micronmol X h-1 to 1.004 +/- 290 micronmol X h-1, respectively. During intraduodenal introduction of meals with pH adjusted from 1.0 to 7.0 in 4 pigs amylase was secreted at all pH levels. However, only when pH of the meal was 1.0, resulting in an intraduodenal pH from 1.0 to 1.7 during the stimulation, was a significant increase in plasma secretin concentration and pancreatic flow rate observed from 5.5 +/- 2.8 pmol X 1(-1) (mean +/- S.E.M.) to 115.0 +/- 51.2 pmol X 1(-1) and from 0.20 +/- 0.08 ml X h-1 to 6.25 +/- 2.57 ml X h-1, respectively.", "contents": "Plasma secretin concentration in anaesthetized pigs after intraduodenal glucose, fat, aminoacids, or meals with various pH. The concentration of immunoreactive secretin in portal blood and the secretion from the exocrine pancreas were measured during intraduodenal infusion of isotonic or hypertonic saline, isotonic or hypertonic glucose, aminoacids, fat emulsion, or 0.1 mol X 1(-1) hydrochloric acid in 7 anaesthetized pigs. None of these substances, except hydrochloric acid, had any effect on plasma secretin concentration and pancreatic flow rate and bicarbonate output. Plasma secretin concentration rose significantly from 5.6 +/- 2.7 pmol X 1(-1) (mean +/- S.E.M.) to a peak value of 201.2 +/- 80.5 pmol X 1(-1) 15 min after infusion of hydrochloric acid. Pancreatic flow rate and bicarbonate output increased from 0.51 +/- 0.19 ml X h-1 (mean +/- S.E.M.) to 9.85 +/- 2.33 ml X h-1 and from 52 +/- 11 micronmol X h-1 to 1.004 +/- 290 micronmol X h-1, respectively. During intraduodenal introduction of meals with pH adjusted from 1.0 to 7.0 in 4 pigs amylase was secreted at all pH levels. However, only when pH of the meal was 1.0, resulting in an intraduodenal pH from 1.0 to 1.7 during the stimulation, was a significant increase in plasma secretin concentration and pancreatic flow rate observed from 5.5 +/- 2.8 pmol X 1(-1) (mean +/- S.E.M.) to 115.0 +/- 51.2 pmol X 1(-1) and from 0.20 +/- 0.08 ml X h-1 to 6.25 +/- 2.57 ml X h-1, respectively."}
{"id": "PMID:17156", "title": "[Bacterial endocarditis: clinical and bacteriological aspects and prognostic factors].", "content": "The microbiological, clinical and therapeutic aspects of all (71) cases of bacterial endocarditis admitted to the H\u00f4pital cantonal, Geneva, between August 1970 and October 1974 were reviewed: there was a definite trend towards higher prevalence of acute cases compared to subacute cases. The pathogenic role of S. epidermidis, mostly in cases of prosthetic valve endocarditis, could be demonstrated in several cases. When defined initially by microbiological criteria only, acute endocarditis were characterized by rapid evolution, destruction of the valvular structures (especially aortic valve), and by further evolution under adequate antibiotic therapy: thus, 10/25 patients with acute endocarditis died, whereas the mortality rate in the subacute cases was only 10/46. Many cases in our series showed one or more often frequent embolic phenomena: 70% of the cured cases and 80% of the patients with a fatal outcome. An unfavorable evolution could be correlated with neurologic involvement, cardiac rhythm or conduction disturbances, and/or heart failure; indeed, heart failure due to various mechanisms was the single most frequent cause of death and is presently the main therapeutic problem. Thus, acute infection leading to destruction of the aortic valve and to heart failure still carries a bad prognosis, even if emergency valve replacement is attempted. Finally, 22/30 patients who developed a bacterial endocarditis after oral or urological procedures knew about a heart murmur, but did not receive antibiotic prophylaxis. This clearly shows that emphasis should be put on the elaboration and diffusion of adequate prophylactic regimens.", "contents": "[Bacterial endocarditis: clinical and bacteriological aspects and prognostic factors]. The microbiological, clinical and therapeutic aspects of all (71) cases of bacterial endocarditis admitted to the H\u00f4pital cantonal, Geneva, between August 1970 and October 1974 were reviewed: there was a definite trend towards higher prevalence of acute cases compared to subacute cases. The pathogenic role of S. epidermidis, mostly in cases of prosthetic valve endocarditis, could be demonstrated in several cases. When defined initially by microbiological criteria only, acute endocarditis were characterized by rapid evolution, destruction of the valvular structures (especially aortic valve), and by further evolution under adequate antibiotic therapy: thus, 10/25 patients with acute endocarditis died, whereas the mortality rate in the subacute cases was only 10/46. Many cases in our series showed one or more often frequent embolic phenomena: 70% of the cured cases and 80% of the patients with a fatal outcome. An unfavorable evolution could be correlated with neurologic involvement, cardiac rhythm or conduction disturbances, and/or heart failure; indeed, heart failure due to various mechanisms was the single most frequent cause of death and is presently the main therapeutic problem. Thus, acute infection leading to destruction of the aortic valve and to heart failure still carries a bad prognosis, even if emergency valve replacement is attempted. Finally, 22/30 patients who developed a bacterial endocarditis after oral or urological procedures knew about a heart murmur, but did not receive antibiotic prophylaxis. This clearly shows that emphasis should be put on the elaboration and diffusion of adequate prophylactic regimens."}
{"id": "PMID:17157", "title": "[Peptic ulcer: new aspects of conservative therapy].", "content": "In spite of the large number of preparations, medical therapy of peptic ulcer disease has long been unsatisfactory. Antacids, anticholinergics and diet neither accelerate healing of ulcers nor prevent recurrences. Carbenoxolone affects only gastric ulcers, while some medications exhibit substantial side effects. Cimetidine, a representative of the new generation of H2-receptor blockers which are potent inhibitors of gastric secretion, significantly enhances healing of duodenal ulcers. In addition, favorable effects on gastric ulcers, as well as on bleeding erosions and ulcers in the Zollinger-Ellison syndrome, have been reported. Thus far no severe adverse reactions with cimetidine have been observed, but data on effects of long term use are lacking. Synthetic prostaglandins are not yet sufficiently evaluated for clinical use.", "contents": "[Peptic ulcer: new aspects of conservative therapy]. In spite of the large number of preparations, medical therapy of peptic ulcer disease has long been unsatisfactory. Antacids, anticholinergics and diet neither accelerate healing of ulcers nor prevent recurrences. Carbenoxolone affects only gastric ulcers, while some medications exhibit substantial side effects. Cimetidine, a representative of the new generation of H2-receptor blockers which are potent inhibitors of gastric secretion, significantly enhances healing of duodenal ulcers. In addition, favorable effects on gastric ulcers, as well as on bleeding erosions and ulcers in the Zollinger-Ellison syndrome, have been reported. Thus far no severe adverse reactions with cimetidine have been observed, but data on effects of long term use are lacking. Synthetic prostaglandins are not yet sufficiently evaluated for clinical use."}
{"id": "PMID:17158", "title": "[Gastro-esophageal reflux disease. A review of pathogenesis, diagnosis and therapy].", "content": "Gastro-esophageal reflux disease is caused by peptic damage from gastric contents to the distal esophagus. The principal cause of reflux is a decrease in pressure of the lower esophageal sphincter, which normally separates the esophagus from the stomach. Various hormonal, pharmacological or toxic agents are capable of altering resting sphincter tone. Treatment of esophageal reflux disease is a rewarding task for the general practitioner. An algorithm on appropriate use of diagnostic and therapeutic resources is presented.", "contents": "[Gastro-esophageal reflux disease. A review of pathogenesis, diagnosis and therapy]. Gastro-esophageal reflux disease is caused by peptic damage from gastric contents to the distal esophagus. The principal cause of reflux is a decrease in pressure of the lower esophageal sphincter, which normally separates the esophagus from the stomach. Various hormonal, pharmacological or toxic agents are capable of altering resting sphincter tone. Treatment of esophageal reflux disease is a rewarding task for the general practitioner. An algorithm on appropriate use of diagnostic and therapeutic resources is presented."}
{"id": "PMID:17159", "title": "Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum.", "content": "Nigral basal adenylate cyclase and dopamine-sensitive adenylate cyclase, glutamate decarboxylase, choline acetyltransferase, and tyrosine hydroxylase activities were measured in rats with hemitransections at various levels or with electrolytic lesions of the medial forebrain bundle or the crus cerebri. The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases. The data indicate that the nigral dopamine-sensitive adenylate cylase activity may be localized on neurons afferent to the nigra, probably originating from the globus pallidus and possibly from the tail of the caudate. The results suggest that dopamine, released from nigral dendrites, may influence dopaminergic activity indirectly by modulating impulses transmitted to the nigrostriatal neurons through the crus cerebri.", "contents": "Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum. Nigral basal adenylate cyclase and dopamine-sensitive adenylate cyclase, glutamate decarboxylase, choline acetyltransferase, and tyrosine hydroxylase activities were measured in rats with hemitransections at various levels or with electrolytic lesions of the medial forebrain bundle or the crus cerebri. The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases. The data indicate that the nigral dopamine-sensitive adenylate cylase activity may be localized on neurons afferent to the nigra, probably originating from the globus pallidus and possibly from the tail of the caudate. The results suggest that dopamine, released from nigral dendrites, may influence dopaminergic activity indirectly by modulating impulses transmitted to the nigrostriatal neurons through the crus cerebri."}
{"id": "PMID:17160", "title": "Transmitter release during repetitive stimulation: selective changes produced by Sr2+ and Ba2+.", "content": "The addition of Sr2+ or Ba2+ to the solution bathing the frog neuromuscular junction leads to an increased release of transmitter by each nerve impulse during and following repetitive stimulation. The mechanisms by which Sr2+ and Ba2+ increase release are not the same. Each ion appears to act selectively on a different process involved in transmitter release.", "contents": "Transmitter release during repetitive stimulation: selective changes produced by Sr2+ and Ba2+. The addition of Sr2+ or Ba2+ to the solution bathing the frog neuromuscular junction leads to an increased release of transmitter by each nerve impulse during and following repetitive stimulation. The mechanisms by which Sr2+ and Ba2+ increase release are not the same. Each ion appears to act selectively on a different process involved in transmitter release."}
{"id": "PMID:17161", "title": "[Periarteritis nodosa and Australia antigen. Comparative study apropos of 25 cases].", "content": "The authors compared two series of 27 cases of p\u00e9riateritis over a period of 5 years. The determined the frequency of the nodosa HBs+ (series B) and HBs-- (series A) collected clinical and laboratory signs in both series. There resulted that apart from the hepatic signs constant in series B and absent in series A, the only statistically significant differences were the joint sings and the hypertension more common in series B and the respiratory signs more common in series A. Furthermore, the course of HBs+ cases appears much mote severe than that of HBs-- cases which emphasises the importance of the hepatic involvement but this finding should be interpreted with circumspection for the mode of selection of the patients and the treatment were different in the two series.", "contents": "[Periarteritis nodosa and Australia antigen. Comparative study apropos of 25 cases]. The authors compared two series of 27 cases of p\u00e9riateritis over a period of 5 years. The determined the frequency of the nodosa HBs+ (series B) and HBs-- (series A) collected clinical and laboratory signs in both series. There resulted that apart from the hepatic signs constant in series B and absent in series A, the only statistically significant differences were the joint sings and the hypertension more common in series B and the respiratory signs more common in series A. Furthermore, the course of HBs+ cases appears much mote severe than that of HBs-- cases which emphasises the importance of the hepatic involvement but this finding should be interpreted with circumspection for the mode of selection of the patients and the treatment were different in the two series."}
{"id": "PMID:17162", "title": "[Beta blockaders and general pathology].", "content": "The authors review the literature on the undesirable side effects of beta blockaders (excluding the cardiovascular system) and report the new therapeutic propects in psychiatry and in various metabolic disorders. The necessity of sufficient follow up made us choose propanolol as reference product without neglecting acebutolol, pindolol and oxprenolol.", "contents": "[Beta blockaders and general pathology]. The authors review the literature on the undesirable side effects of beta blockaders (excluding the cardiovascular system) and report the new therapeutic propects in psychiatry and in various metabolic disorders. The necessity of sufficient follow up made us choose propanolol as reference product without neglecting acebutolol, pindolol and oxprenolol."}
{"id": "PMID:17164", "title": "Expression of differentiated functions in hepatoma cell hybrids: IX extinction and reexpression of liver-specific enzymes in rat hepatoma-Chinese hamster fibroblast hybrids.", "content": "Most of the hybrid clones derived from a cross of Chinese hamster fibroblasts (DON) with rat hepatoma cells (Faza 967) showed preferential loss of rat chromosomes. Two of the hybrid clones retained the rat chromosomes, and both showed extinction of 4 liver-specific enzymes: aldolase B, liver alcohol dehydrogenase, and the inducible enzymes tyrosine aminotransferase and alanine aminotransferase. Subcloning of 1 of these hybrids, which contained 2 sets of hepatoma chromosomes and 1 set of hamster chromosomes, permitted the isolation of some clones which reexpressed 1 or more of the liver-specific enzymes. Liver alcohol dehydrogenase was the most frequently reexpressed enzyme and aldolase B the least. Tyrosine aminotransferase inducibility was reexpressed independently of basal activity, and the enzyme produced by the reexpressing hybrid cells was precipitated by a specific antiserum. No correlation was detected between the presence or absence of the marker chromosomes (large metacentrics) of the hamster parent and the extinction and reexpression of the hepatic enzymes. The results reported confirm and extend to interspecific hybrids the observation of the stable and independent reexpression of tissue-specific enzymes.", "contents": "Expression of differentiated functions in hepatoma cell hybrids: IX extinction and reexpression of liver-specific enzymes in rat hepatoma-Chinese hamster fibroblast hybrids. Most of the hybrid clones derived from a cross of Chinese hamster fibroblasts (DON) with rat hepatoma cells (Faza 967) showed preferential loss of rat chromosomes. Two of the hybrid clones retained the rat chromosomes, and both showed extinction of 4 liver-specific enzymes: aldolase B, liver alcohol dehydrogenase, and the inducible enzymes tyrosine aminotransferase and alanine aminotransferase. Subcloning of 1 of these hybrids, which contained 2 sets of hepatoma chromosomes and 1 set of hamster chromosomes, permitted the isolation of some clones which reexpressed 1 or more of the liver-specific enzymes. Liver alcohol dehydrogenase was the most frequently reexpressed enzyme and aldolase B the least. Tyrosine aminotransferase inducibility was reexpressed independently of basal activity, and the enzyme produced by the reexpressing hybrid cells was precipitated by a specific antiserum. No correlation was detected between the presence or absence of the marker chromosomes (large metacentrics) of the hamster parent and the extinction and reexpression of the hepatic enzymes. The results reported confirm and extend to interspecific hybrids the observation of the stable and independent reexpression of tissue-specific enzymes."}
{"id": "PMID:17165", "title": "Extinction of liver-specific functions in hybrids between differentiated and dedifferentiated rat hepatoma cells.", "content": "A cross has been performed between dedifferentiated rat hepatoma cells and the differentiated cells from which they were derived. 10 hybrid clones, containing the complete chromosome sets of both parents, show extinction of 4 liver-specific enzymes: tyrosine aminotransferase (E.C. 2.6.1.5), alanine aminotransferase (E.C. 2.6.1.2), and the liver-specific isozymes of alcohol dehydrogenase (E.C. 1.1.1.1) and aldolase (E.C. 4.1.2.13). Moreover, the 4 hybrid clones examined do not produce albumin . The only function of the differentiated parent which is not extinguished in the hybrid cells is inducibility of the aminotransferases. For 3 of the hybrid clones, extinction of 3 of the 4 enzymes is incomplete, but these clones do not differ in modal chromosome number from those which show more complete extinction of the enzymes. Subcloning of several of the hybrids revealed that the phenotype of the hybrids is very stable; 4 subclones showing reexpression of intermediate levels of the enzymes are characterized. These results show that dedifferentiation of the parental cells is not due to the simple loss of some factor required for the maintenance of expression of differentiated functions, and suggest that dedifferentiation is due to the activation of some control mechanism, whose final effect is negative, and which may be a part of the epigenotype of the embryonic hepatocyte.", "contents": "Extinction of liver-specific functions in hybrids between differentiated and dedifferentiated rat hepatoma cells. A cross has been performed between dedifferentiated rat hepatoma cells and the differentiated cells from which they were derived. 10 hybrid clones, containing the complete chromosome sets of both parents, show extinction of 4 liver-specific enzymes: tyrosine aminotransferase (E.C. 2.6.1.5), alanine aminotransferase (E.C. 2.6.1.2), and the liver-specific isozymes of alcohol dehydrogenase (E.C. 1.1.1.1) and aldolase (E.C. 4.1.2.13). Moreover, the 4 hybrid clones examined do not produce albumin . The only function of the differentiated parent which is not extinguished in the hybrid cells is inducibility of the aminotransferases. For 3 of the hybrid clones, extinction of 3 of the 4 enzymes is incomplete, but these clones do not differ in modal chromosome number from those which show more complete extinction of the enzymes. Subcloning of several of the hybrids revealed that the phenotype of the hybrids is very stable; 4 subclones showing reexpression of intermediate levels of the enzymes are characterized. These results show that dedifferentiation of the parental cells is not due to the simple loss of some factor required for the maintenance of expression of differentiated functions, and suggest that dedifferentiation is due to the activation of some control mechanism, whose final effect is negative, and which may be a part of the epigenotype of the embryonic hepatocyte."}
{"id": "PMID:17163", "title": "In vitro inhibition of growth of neisseria gonorrhoeae by genital microorganisms.", "content": "The ability of microorganisms present in titers of over 10(5)/ml in the vaginal or cervical secretions to inhibit growth of N. gonorrhoeae in vitro was tested. Study of a strain of N. gonorrhoeae against 77 microorganisms demonstrated that most strans of S. epidermidis, S. aureus and the one \"Gaffkya anaerobia\" interfered with the growth of the N. gonorrhoeae. A minority of strains of S. viridans, Neisseria, Candida and Bifidobacterium demonstrated interference. No strains of enterococcus, diptheroids, aerobic Lactobacillus, Peptostreptococcus, Peptococcus, anaerobic Lactobacillus or Veillonella demonstrated interference.", "contents": "In vitro inhibition of growth of neisseria gonorrhoeae by genital microorganisms. The ability of microorganisms present in titers of over 10(5)/ml in the vaginal or cervical secretions to inhibit growth of N. gonorrhoeae in vitro was tested. Study of a strain of N. gonorrhoeae against 77 microorganisms demonstrated that most strans of S. epidermidis, S. aureus and the one \"Gaffkya anaerobia\" interfered with the growth of the N. gonorrhoeae. A minority of strains of S. viridans, Neisseria, Candida and Bifidobacterium demonstrated interference. No strains of enterococcus, diptheroids, aerobic Lactobacillus, Peptostreptococcus, Peptococcus, anaerobic Lactobacillus or Veillonella demonstrated interference."}
{"id": "PMID:17180", "title": "Reduction of fatal graft-versus-host disease by 3H-thymidine suicide of donor cells cultured with host cells.", "content": "The effect of the tritiated thymidine (3H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2b) spleen cells were stimulated in vitro with irradiated BALB/c (H-2d) Moloney lymphoma cells in mixed culture and 3H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 per cent) than did C57BL/6 cells cultures with BALB/C lymphoma cells but without 3H-TdR (87%) and C57BL/L cells cultured with irradiated C57BL/6 cells with (95 per cent) or without 3H-TdR (86 per cent). Thus, the 3H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD.", "contents": "Reduction of fatal graft-versus-host disease by 3H-thymidine suicide of donor cells cultured with host cells. The effect of the tritiated thymidine (3H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2b) spleen cells were stimulated in vitro with irradiated BALB/c (H-2d) Moloney lymphoma cells in mixed culture and 3H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 per cent) than did C57BL/6 cells cultures with BALB/C lymphoma cells but without 3H-TdR (87%) and C57BL/L cells cultured with irradiated C57BL/6 cells with (95 per cent) or without 3H-TdR (86 per cent). Thus, the 3H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD."}
{"id": "PMID:17181", "title": "In vivo and in vitro effects of acute graft-versus-host serum in the rat.", "content": "Pooled serum from 6- to 8-week-old female Lewis x Brown Norwegian F1 hybrid (LBNF1) rats undergoing acute local graft-versus-host (GVH) reactions was found to have the ability, when compared with normal F1 serum, to increase node weight in a popliteal lymph node weight gain assay in syngeneic animals. Suspension of donor cells in normal F1 serum on one side and corresponding concentrations of GVH serum on the contralateral side resulted in an average increase in popliteal node weight of 28.8 per cent on the side receiving GVH serum. Of the 64 animals tested, 50 had larger nodes on the GVH serum side. This effect was not impaired by heating (56 C, 30 min) or by rapid freezing (-75 C) and thawing of the serum. Preinjection of the serum into the footpads 2 hr before donor cells also gave increased node weights as did injection of the serum i.p. In contrast, GVH serum was found to inhibit unidirectional mixed lymphocyte cultures of seven different allogeneic rat strain combinations, the inhibition ranging from 35 to 74 per cent. In addition, the blastogenic cell responses of three different strains to phytohemagglutinin P were inhibited between 45 and 77 per cent. The relationship between these two phenomena, in vivo increase in node weight and in vitro inhibition of blastogenesis, is not clear and is the object of further investigation.", "contents": "In vivo and in vitro effects of acute graft-versus-host serum in the rat. Pooled serum from 6- to 8-week-old female Lewis x Brown Norwegian F1 hybrid (LBNF1) rats undergoing acute local graft-versus-host (GVH) reactions was found to have the ability, when compared with normal F1 serum, to increase node weight in a popliteal lymph node weight gain assay in syngeneic animals. Suspension of donor cells in normal F1 serum on one side and corresponding concentrations of GVH serum on the contralateral side resulted in an average increase in popliteal node weight of 28.8 per cent on the side receiving GVH serum. Of the 64 animals tested, 50 had larger nodes on the GVH serum side. This effect was not impaired by heating (56 C, 30 min) or by rapid freezing (-75 C) and thawing of the serum. Preinjection of the serum into the footpads 2 hr before donor cells also gave increased node weights as did injection of the serum i.p. In contrast, GVH serum was found to inhibit unidirectional mixed lymphocyte cultures of seven different allogeneic rat strain combinations, the inhibition ranging from 35 to 74 per cent. In addition, the blastogenic cell responses of three different strains to phytohemagglutinin P were inhibited between 45 and 77 per cent. The relationship between these two phenomena, in vivo increase in node weight and in vitro inhibition of blastogenesis, is not clear and is the object of further investigation."}
{"id": "PMID:17182", "title": "Generation of suppressor cells in mice immunized with M locus-incompatible lymphocytes.", "content": "Alloimmunization of mice with M locus-incompatible lymphocytes resulted in the generation of suppressor cells in the immunized host. Lymph node cells from such alloimmunized mice suppressed the in vitro cytotoxic response of normal cells to H-2 alloantigens. The suppression generated was greater than could be accounted for by dilution of the prekiller cell population with cells possibly devoid of cytotoxic potential from M locus preimmunized mice. Using M locus pseudocongenic mice, the suppressive effect was shown to be largely attributable to M locus determinants; restimulation of suppressor cells in culture with the specific M locus was required for suppression of effector cell generation. The in vivo effect of suppressor cells was tested in a graft-versus-host reaction; injection of M locus preimmunized cells into footpads of F1 hybrid mice suppressed the popliteal lymph node enlargement compared with lymph node size after injection of control preimmunized cells. Although the suppressive effect is mainly attributable to M locus determinants, incompatibility for the DBA/2 antigen may add to the suppression. The study of inhibitory effects on T cell cytotoxicity because of serologically undetectable lymphocyte-activating determinants (Mls) could lead to the better understanding of suppressive mechanisms which may allow the growth of syngeneic tumours.", "contents": "Generation of suppressor cells in mice immunized with M locus-incompatible lymphocytes. Alloimmunization of mice with M locus-incompatible lymphocytes resulted in the generation of suppressor cells in the immunized host. Lymph node cells from such alloimmunized mice suppressed the in vitro cytotoxic response of normal cells to H-2 alloantigens. The suppression generated was greater than could be accounted for by dilution of the prekiller cell population with cells possibly devoid of cytotoxic potential from M locus preimmunized mice. Using M locus pseudocongenic mice, the suppressive effect was shown to be largely attributable to M locus determinants; restimulation of suppressor cells in culture with the specific M locus was required for suppression of effector cell generation. The in vivo effect of suppressor cells was tested in a graft-versus-host reaction; injection of M locus preimmunized cells into footpads of F1 hybrid mice suppressed the popliteal lymph node enlargement compared with lymph node size after injection of control preimmunized cells. Although the suppressive effect is mainly attributable to M locus determinants, incompatibility for the DBA/2 antigen may add to the suppression. The study of inhibitory effects on T cell cytotoxicity because of serologically undetectable lymphocyte-activating determinants (Mls) could lead to the better understanding of suppressive mechanisms which may allow the growth of syngeneic tumours."}
{"id": "PMID:17183", "title": "HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases.", "content": "Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.", "contents": "HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases. Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation."}
{"id": "PMID:17185", "title": "A comparison of immune responses against AG-B and non-AG-B antigens, presented alone or together.", "content": "By exploiting congenic rat strains (HO.B2 and PVG/c) cell-mediated immune responses against Ag-B antigens alone were measured and compared with responses against (1) non-Ag-B antigens and (2) Ag-B and non-Ag-B antigens in combination. It was confirmed that multiple non-Ag-B antigens provoke prompt first-set skin graft rejections, but are much weaker than Ag-B antigens in stimulating both graft-versus-host (GVH) and cytotoxic activity. No evidence of synergistic interaction was found between anti-Ag-B and anti-non-Ag-B responses either by GVH assay or in the generation of cytotoxic cells. Specific partitioning of cytotoxic cells on antigenic monolayers suggested that cytotoxic cells on antigenic monolayers suggested that cytotoxicity is predominantly directed against Ag-B antigens. The measurements of GVH activity consolidate previous work, which suggested that 4.5 to 12% of nonimmune T cells can respond to each Ag-B determined antigenic complex and eliminate the possibility that most of these cells were responding to non-Ag-B antigens. Two principles for measuring GVH activity were compared: (1) 3H-thymidine incorporation into donor lymphocytes at 24 hr after transfer to irradiated F1 hybrid recipients and (2) the popliteal lymph node assay, which depends on a secondary phase of host cell proliferation.", "contents": "A comparison of immune responses against AG-B and non-AG-B antigens, presented alone or together. By exploiting congenic rat strains (HO.B2 and PVG/c) cell-mediated immune responses against Ag-B antigens alone were measured and compared with responses against (1) non-Ag-B antigens and (2) Ag-B and non-Ag-B antigens in combination. It was confirmed that multiple non-Ag-B antigens provoke prompt first-set skin graft rejections, but are much weaker than Ag-B antigens in stimulating both graft-versus-host (GVH) and cytotoxic activity. No evidence of synergistic interaction was found between anti-Ag-B and anti-non-Ag-B responses either by GVH assay or in the generation of cytotoxic cells. Specific partitioning of cytotoxic cells on antigenic monolayers suggested that cytotoxic cells on antigenic monolayers suggested that cytotoxicity is predominantly directed against Ag-B antigens. The measurements of GVH activity consolidate previous work, which suggested that 4.5 to 12% of nonimmune T cells can respond to each Ag-B determined antigenic complex and eliminate the possibility that most of these cells were responding to non-Ag-B antigens. Two principles for measuring GVH activity were compared: (1) 3H-thymidine incorporation into donor lymphocytes at 24 hr after transfer to irradiated F1 hybrid recipients and (2) the popliteal lymph node assay, which depends on a secondary phase of host cell proliferation."}
{"id": "PMID:17186", "title": "The graft-versus-host reactivity in AG-B/MLR disparate strains of rats.", "content": "Inbred strains of rats can currently be classified into eight Ag-B groups. Within an Ag-B group, individual strains generally share identity both the Ag-B histocompatibility antigens and mixed lymphocyte responses. In this report we present data from three strains which are Ag-B and mixed lymphocyte reaction (MLR) disparate: KGH (Ag-B7, MLR-1), MNR (Ag-B4, MLR-5), and B3 (Ag-B3, MLR-4). Popliteal lymph node assays involving these three strains and standard inbred strains demonstrate that the graft-versus-host reaction and MLR reactions in the rat are closely related. Positive graft-versus-host reactions were observed only in strain combinations incompatible for the MLR and were unaffected by differences in their Ag-B histocompatibility antigens. The close association of the MLR and graft-versus-host reaction provides additional evidence that the Ag-B/MLR disparity in these strains is the result of natural genetic recombinations within the major histocompatibility complex.", "contents": "The graft-versus-host reactivity in AG-B/MLR disparate strains of rats. Inbred strains of rats can currently be classified into eight Ag-B groups. Within an Ag-B group, individual strains generally share identity both the Ag-B histocompatibility antigens and mixed lymphocyte responses. In this report we present data from three strains which are Ag-B and mixed lymphocyte reaction (MLR) disparate: KGH (Ag-B7, MLR-1), MNR (Ag-B4, MLR-5), and B3 (Ag-B3, MLR-4). Popliteal lymph node assays involving these three strains and standard inbred strains demonstrate that the graft-versus-host reaction and MLR reactions in the rat are closely related. Positive graft-versus-host reactions were observed only in strain combinations incompatible for the MLR and were unaffected by differences in their Ag-B histocompatibility antigens. The close association of the MLR and graft-versus-host reaction provides additional evidence that the Ag-B/MLR disparity in these strains is the result of natural genetic recombinations within the major histocompatibility complex."}
{"id": "PMID:17188", "title": "Bone marrow transplantation.", "content": "Improvements in the results of bone marrow transplantation for the treatment of SCID may be expected by employing purified stem-cell concentrates for patients who do not have a compatible sibling available. Refinements in the purification technique and its monitoring are required, however. For the same category of patients it seems worthwhile to continue attempts at restoration with liver cells from fetuses less than 12 weeks of age. In addition, full protection against infections should be provided for patients expected to develop GVHD, and, therefore, such patients should only be treated in centers where reverse isolation and bacteriologic decontamination can be performed. In view of the rarity of the disease, transplanters should agree on a limited number of graft protocols. For the treatment of bone marrow aplasia, attempts to identify the factors that can serve to predict the occurrence of GVHD in compatible host-donor sibling pairs should be continued. Only when the patients who will develop GVHD can be recognized in advance will it be feasible to fully exploit available GVHD reductive measures. In particular the role of the intestinal microflora should be investigated in this respect. Experimental evidence is presented, suggesting an aggravating influence of microflora on GVHD lesions, which are primarily induced by histocompatibility reactions. For such studies with incompatible siblings, the dog is the best available animal model. For the selective isolation of hemopoietic stem cells for transplantation purposes (as one means of reducing GVHD), methods for rapid identification of stem cells and immune competent cells, respectively, have to be developed. In leukemia, more research is necessary on the factors that play a role in the late complications of bone marrow transplantation. The toxicity of aggressive regimens employed in the eradication of the leukemia should be further analyzed. The collection of autologous normal hemopoietic stem cells from leukemic patients as introduced by Dicke et al. warrants further exploration to see whether these cells may replace the allogeneic transplantation procedure, thus avoiding all the complications generally encountered in GVHD. For all three diseases, it is extremely important to develop a method for the selection of compatible donors among unrelated individuals, because this will at least double the number of candidates for therapeutic bone marrow transplantation. Current progress in histocompatibility typing in the rhesus monkey and the dog makes these species excellent models for such investigations.", "contents": "Bone marrow transplantation. Improvements in the results of bone marrow transplantation for the treatment of SCID may be expected by employing purified stem-cell concentrates for patients who do not have a compatible sibling available. Refinements in the purification technique and its monitoring are required, however. For the same category of patients it seems worthwhile to continue attempts at restoration with liver cells from fetuses less than 12 weeks of age. In addition, full protection against infections should be provided for patients expected to develop GVHD, and, therefore, such patients should only be treated in centers where reverse isolation and bacteriologic decontamination can be performed. In view of the rarity of the disease, transplanters should agree on a limited number of graft protocols. For the treatment of bone marrow aplasia, attempts to identify the factors that can serve to predict the occurrence of GVHD in compatible host-donor sibling pairs should be continued. Only when the patients who will develop GVHD can be recognized in advance will it be feasible to fully exploit available GVHD reductive measures. In particular the role of the intestinal microflora should be investigated in this respect. Experimental evidence is presented, suggesting an aggravating influence of microflora on GVHD lesions, which are primarily induced by histocompatibility reactions. For such studies with incompatible siblings, the dog is the best available animal model. For the selective isolation of hemopoietic stem cells for transplantation purposes (as one means of reducing GVHD), methods for rapid identification of stem cells and immune competent cells, respectively, have to be developed. In leukemia, more research is necessary on the factors that play a role in the late complications of bone marrow transplantation. The toxicity of aggressive regimens employed in the eradication of the leukemia should be further analyzed. The collection of autologous normal hemopoietic stem cells from leukemic patients as introduced by Dicke et al. warrants further exploration to see whether these cells may replace the allogeneic transplantation procedure, thus avoiding all the complications generally encountered in GVHD. For all three diseases, it is extremely important to develop a method for the selection of compatible donors among unrelated individuals, because this will at least double the number of candidates for therapeutic bone marrow transplantation. Current progress in histocompatibility typing in the rhesus monkey and the dog makes these species excellent models for such investigations."}
{"id": "PMID:17192", "title": "Specific absorbed antithymocyte globulin for incubation treatment in human marrow transplantation.", "content": "The experimental data show that absorption of ATG with liver-kidney homogenate and CLL and LCL cells stepwise removed the hemopoietic toxicity, whereas the specific activity against T lymphocytes remained. Although the mode of action of absorbed ATG could not be tested in the first clinical case, the successful experiments in rodents together with the fact that the incubation treatment was tolerated by the patient may provide a new way of preventing fatal GVH reactions in man.", "contents": "Specific absorbed antithymocyte globulin for incubation treatment in human marrow transplantation. The experimental data show that absorption of ATG with liver-kidney homogenate and CLL and LCL cells stepwise removed the hemopoietic toxicity, whereas the specific activity against T lymphocytes remained. Although the mode of action of absorbed ATG could not be tested in the first clinical case, the successful experiments in rodents together with the fact that the incubation treatment was tolerated by the patient may provide a new way of preventing fatal GVH reactions in man."}
{"id": "PMID:17198", "title": "Other mammalian histocompatibility systems. Skin graft rejection and graft-versus-host reaction across I-subregion differences: are there many more than three H loci within the H-2 complex?", "content": "The data confirm an earlier finding by Klein et al. that the I region harbors a strong histocompatibility locus, which by exclusion might be assigned to the IA subregion. In addition, it appears that intercalated between the IA subregion and S region there is a minor H locus since (DBA/2 X 4R)F1 rejects skin of 2R in a chronic fashion. In another combination, HTT versus 7R, which differs for the IC, S, and G regions but may also differ for genes between the D and TL locus, a similar chronic rejection pattern was observed indicating minor H gene(s) within or closely linked to the H-2 complex. The data reported here are in concordance with very recently published results by Klein et al..", "contents": "Other mammalian histocompatibility systems. Skin graft rejection and graft-versus-host reaction across I-subregion differences: are there many more than three H loci within the H-2 complex? The data confirm an earlier finding by Klein et al. that the I region harbors a strong histocompatibility locus, which by exclusion might be assigned to the IA subregion. In addition, it appears that intercalated between the IA subregion and S region there is a minor H locus since (DBA/2 X 4R)F1 rejects skin of 2R in a chronic fashion. In another combination, HTT versus 7R, which differs for the IC, S, and G regions but may also differ for genes between the D and TL locus, a similar chronic rejection pattern was observed indicating minor H gene(s) within or closely linked to the H-2 complex. The data reported here are in concordance with very recently published results by Klein et al.."}
{"id": "PMID:17213", "title": "Nuclear and cytoplasmic RNase-activity in regenerating mouse liver.", "content": "Nuclear and cytoplasmic RNase activities at pH 5.0 and 7.6 were analyzed in regenerating mouse liver at 6, 12, 24, 48, and 72 h after partial hepatectomy. Two different nucleus-isolation methods were used, one in a EDTA-spermidine medium free from divalent cations, and one in a sucrose medium containing these ions. During regeneration, the cytoplasmic alkaline RNase activity in the sucrose medium was unchanged, but in the spermidine medium showed an increase toward the end of the period. Also the cytoplasmic acid RNase activity was unchanged in sucrose medium, whereas in the spermidine it slightly increased during regeneration. The nuclear alkaline RNase activity showed a notable peak 6 h after the operation and later decreased. Also the nuclear acid RNase activity displayed a similar marked peak 6 h after operation, then decreased, but remained high throughout the period. The nuclear RNase activities were about 1% of the corresponding cytoplasmic RNase activities. The absolute activities varied greatly according to the nucleus-isolation methods. In the controls, the absolute activity of nuclear alkaline RNase was slightly above (1.2 times) that of the corresponding acid activity after the spermidine method. After the sucrose method the nuclear alkaline activity was 2.7 times that of the acid activity. The absoluted activity of cytoplasmic alkaline RNase was slightly above (1.2 times) the acid activity after the spermidine method but after the sucrose method it was only 0.25 times that of the acid activity. In sham-operated animals, cytoplasmic acid and alkaline RNase activities generally were fairly similar to the normal value, but corresponding nuclear activities showed marked variations indicating an influence by anesthesia.", "contents": "Nuclear and cytoplasmic RNase-activity in regenerating mouse liver. Nuclear and cytoplasmic RNase activities at pH 5.0 and 7.6 were analyzed in regenerating mouse liver at 6, 12, 24, 48, and 72 h after partial hepatectomy. Two different nucleus-isolation methods were used, one in a EDTA-spermidine medium free from divalent cations, and one in a sucrose medium containing these ions. During regeneration, the cytoplasmic alkaline RNase activity in the sucrose medium was unchanged, but in the spermidine medium showed an increase toward the end of the period. Also the cytoplasmic acid RNase activity was unchanged in sucrose medium, whereas in the spermidine it slightly increased during regeneration. The nuclear alkaline RNase activity showed a notable peak 6 h after the operation and later decreased. Also the nuclear acid RNase activity displayed a similar marked peak 6 h after operation, then decreased, but remained high throughout the period. The nuclear RNase activities were about 1% of the corresponding cytoplasmic RNase activities. The absolute activities varied greatly according to the nucleus-isolation methods. In the controls, the absolute activity of nuclear alkaline RNase was slightly above (1.2 times) that of the corresponding acid activity after the spermidine method. After the sucrose method the nuclear alkaline activity was 2.7 times that of the acid activity. The absoluted activity of cytoplasmic alkaline RNase was slightly above (1.2 times) the acid activity after the spermidine method but after the sucrose method it was only 0.25 times that of the acid activity. In sham-operated animals, cytoplasmic acid and alkaline RNase activities generally were fairly similar to the normal value, but corresponding nuclear activities showed marked variations indicating an influence by anesthesia."}
{"id": "PMID:17208", "title": "[Characteristics of the serum proteins of cancer patients in an acid medium].", "content": "Under condition of nitric acid titration of aqueous and hydrochloride solutions of sera from patients with cancer certain serum proteins become insoluble at higher values of pH as compared to the other proteins of sera. The latter lose solubility at the pH values corresponding to transition to the insoluble state of serum proteins from people without malignant tumours. The results of studies in the temperature regime effect on the found peculiarities of serum proteins from patients with cancer in the acid medium permit assuming that the physical bases of the marked transitions are different. The mentioned regularity is not pronounced with a temperature rise up to 35--40 degree C.", "contents": "[Characteristics of the serum proteins of cancer patients in an acid medium]. Under condition of nitric acid titration of aqueous and hydrochloride solutions of sera from patients with cancer certain serum proteins become insoluble at higher values of pH as compared to the other proteins of sera. The latter lose solubility at the pH values corresponding to transition to the insoluble state of serum proteins from people without malignant tumours. The results of studies in the temperature regime effect on the found peculiarities of serum proteins from patients with cancer in the acid medium permit assuming that the physical bases of the marked transitions are different. The mentioned regularity is not pronounced with a temperature rise up to 35--40 degree C."}
{"id": "PMID:17209", "title": "[ATPase activity and fluorescence of myometrial actomyosin in experimental uterine inertia].", "content": "A comparative study was performed for actomyosin complexes of the female rabbit myometrium in the state of labour (actomyosin of the control) and secondary uterine inertia (actomyosin of the model). Under the secondary uterine inertia the activity of actomyosin Ca2+- and Mg2+-ATPase decreases. When pH of the medium changes, ATPase of control actomyosin has two peaks of the activity: at rH 6.0 and pH 9.0, that of the model at pH 6.0. Actomyosin of the model and control differs by a degree and rate of superprecipitation, thermal stability and structure. It is supposed that the structural changes in actomyosin under the secondary uterine inertia occur due to accumulation of the metabolism products, the level of which with this pathology is beyond the limits of the adaptation potentialities of the organism.", "contents": "[ATPase activity and fluorescence of myometrial actomyosin in experimental uterine inertia]. A comparative study was performed for actomyosin complexes of the female rabbit myometrium in the state of labour (actomyosin of the control) and secondary uterine inertia (actomyosin of the model). Under the secondary uterine inertia the activity of actomyosin Ca2+- and Mg2+-ATPase decreases. When pH of the medium changes, ATPase of control actomyosin has two peaks of the activity: at rH 6.0 and pH 9.0, that of the model at pH 6.0. Actomyosin of the model and control differs by a degree and rate of superprecipitation, thermal stability and structure. It is supposed that the structural changes in actomyosin under the secondary uterine inertia occur due to accumulation of the metabolism products, the level of which with this pathology is beyond the limits of the adaptation potentialities of the organism."}
{"id": "PMID:17219", "title": "[Intracellular nucleodepolymerase of bacteria, representatives of the Proteus and Providencia groups. Its isolation and properties].", "content": "High activity of enzymes, splitting native, denaturated DNA, deoxyribooligonucleotides and RNA, was observed in cell free extracts of bacteria--representatives of 5 strains of Proteus-Providencia. Some properties of nucleases were studied in cell free extracts. In the bacteria studied DNAases were thermolabile proteins, which were completely inactivated at 50-60 degrees, RNAases were more thermostable. The pH optima of the DNAases were at pH 9.0-11.0 in cell free system; RNAases were maximally active at pH 8.0-9.0", "contents": "[Intracellular nucleodepolymerase of bacteria, representatives of the Proteus and Providencia groups. Its isolation and properties]. High activity of enzymes, splitting native, denaturated DNA, deoxyribooligonucleotides and RNA, was observed in cell free extracts of bacteria--representatives of 5 strains of Proteus-Providencia. Some properties of nucleases were studied in cell free extracts. In the bacteria studied DNAases were thermolabile proteins, which were completely inactivated at 50-60 degrees, RNAases were more thermostable. The pH optima of the DNAases were at pH 9.0-11.0 in cell free system; RNAases were maximally active at pH 8.0-9.0"}
{"id": "PMID:17220", "title": "[Role of divalent cations in the structural organization of the peroxisomal membrane].", "content": "Factors, which affected the stability of peroxisomal membrane in vitro, were investigated. The decrease in the activity of catalase at neutral and alkaline pH was prevented by addition of Ca2+, Mg2+ and Ba2+; at the same time EDTA, EGTA and o-phenantroline decreased the stability of peroxisomes. All the effects were temperature-dependent. Ca2+ did not prevent the injury of peroxisomes during hypotonic lysis, but increased the electrostatic interactions of enzymes with the peroxisomal membrane. These data suggest that at neutral and alkaline pH the peroxisomal membranes had a large negative charge on their surface, which affected the stability of peroxisomes in vitro.", "contents": "[Role of divalent cations in the structural organization of the peroxisomal membrane]. Factors, which affected the stability of peroxisomal membrane in vitro, were investigated. The decrease in the activity of catalase at neutral and alkaline pH was prevented by addition of Ca2+, Mg2+ and Ba2+; at the same time EDTA, EGTA and o-phenantroline decreased the stability of peroxisomes. All the effects were temperature-dependent. Ca2+ did not prevent the injury of peroxisomes during hypotonic lysis, but increased the electrostatic interactions of enzymes with the peroxisomal membrane. These data suggest that at neutral and alkaline pH the peroxisomal membranes had a large negative charge on their surface, which affected the stability of peroxisomes in vitro."}
{"id": "PMID:17222", "title": "[Labilization of lysosomal and peroxisomal membranes in the kidneys preserved by transrenal gas perfusion].", "content": "The total, free and unprecipitated activity of lysosomal (acid DNAase, acid RNAase, acid phosphate, acid beta-galactosidase) and peroxisomal (catalase, oxidase of D-amino acids) enzymes were studied in dog kidney cortex during storage of the tissues in solution of rheopolyglucin and under conservation of the kidney tissue by transrenal gas perfusion in hypothermia within 3 and 7 days. Labilization of lysosomal and peroxisomal membranes was observed during storage both in unperfused and in oxygenated kidney. Mechanisms of formation and functional significance of the alterations observed in structure of lysosomes and peroxisomes are discussed.", "contents": "[Labilization of lysosomal and peroxisomal membranes in the kidneys preserved by transrenal gas perfusion]. The total, free and unprecipitated activity of lysosomal (acid DNAase, acid RNAase, acid phosphate, acid beta-galactosidase) and peroxisomal (catalase, oxidase of D-amino acids) enzymes were studied in dog kidney cortex during storage of the tissues in solution of rheopolyglucin and under conservation of the kidney tissue by transrenal gas perfusion in hypothermia within 3 and 7 days. Labilization of lysosomal and peroxisomal membranes was observed during storage both in unperfused and in oxygenated kidney. Mechanisms of formation and functional significance of the alterations observed in structure of lysosomes and peroxisomes are discussed."}
{"id": "PMID:17223", "title": "[Role of salivary ribonuclease in pathogenesis of periodontosis].", "content": "In patients with periodontal disease a distinct increase in secretion of salivary acidic and alkaline RNAases was found. The RNAases activity in mixed saliva correlated with the intensity of degradation of periodontal tissues during loss of alveolar layer in aged Wistar rats and the spontaneous periodontal disease in cats. In experiments with golden hamsters salivary RNAase was found to penetrate through mucosa in active form. The purified salivary RNAase inhibited the protein biosynthesis in rabbit gingiva. Intensive atrophic alterations were produced in periodontal tissues of Wistar rats by means of purified salivary RNAase.", "contents": "[Role of salivary ribonuclease in pathogenesis of periodontosis]. In patients with periodontal disease a distinct increase in secretion of salivary acidic and alkaline RNAases was found. The RNAases activity in mixed saliva correlated with the intensity of degradation of periodontal tissues during loss of alveolar layer in aged Wistar rats and the spontaneous periodontal disease in cats. In experiments with golden hamsters salivary RNAase was found to penetrate through mucosa in active form. The purified salivary RNAase inhibited the protein biosynthesis in rabbit gingiva. Intensive atrophic alterations were produced in periodontal tissues of Wistar rats by means of purified salivary RNAase."}
{"id": "PMID:17227", "title": "Subtypes of depression--diagnosis and medical management.", "content": "Depression is both a common and a greatly undertreated illness in the United States today. The focus of this review is a definition of the characteristics of four subtypes of depression which appear to be differentially sensitive to four different classes of medications. The tricyclic antidepressants should be used for patients with unipolar depression and vegetative symptoms. Lithium appears to be most effective for bipolar depressives. The monoamine oxidase (MAO) inhibitors are best used for patients with atypical depression. Antipsychotic medications appear to be useful for depressed patients with psychotic symptoms or agitation. Recent pharmacokinetic and biochemical data, including serum lithium levels, plasma tricyclic levels, and the predictive ability of pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels are also reviewed.", "contents": "Subtypes of depression--diagnosis and medical management. Depression is both a common and a greatly undertreated illness in the United States today. The focus of this review is a definition of the characteristics of four subtypes of depression which appear to be differentially sensitive to four different classes of medications. The tricyclic antidepressants should be used for patients with unipolar depression and vegetative symptoms. Lithium appears to be most effective for bipolar depressives. The monoamine oxidase (MAO) inhibitors are best used for patients with atypical depression. Antipsychotic medications appear to be useful for depressed patients with psychotic symptoms or agitation. Recent pharmacokinetic and biochemical data, including serum lithium levels, plasma tricyclic levels, and the predictive ability of pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels are also reviewed."}
{"id": "PMID:17221", "title": "[New variant of glucose-6-phosphate dehydrogenase (G-6-PD \"Kaluga\") from erythrocytes of a patient with chronic nonspherocytic hemolytic anemia].", "content": "Properties of a new form of glucose-6-phosphate dehydrogenase (G6PD) from erythrocytes, called \"Kaluga\", are described. The enzyme was isolated from erythrocytes of a patient with chronic non-spherocytic hemolytic anemia; in the blood cells 20% of the G6PD activity was maintained as compared with normal state. The partially purified enzyme was shown to be unstable in electrophoresis, it possessed a biphase type of pH-optima; Km value for NADP was decreased for glucose-6-phosphate Km value was normal. The thermostability of G6PD was normal at 46 within 1 hr.", "contents": "[New variant of glucose-6-phosphate dehydrogenase (G-6-PD \"Kaluga\") from erythrocytes of a patient with chronic nonspherocytic hemolytic anemia]. Properties of a new form of glucose-6-phosphate dehydrogenase (G6PD) from erythrocytes, called \"Kaluga\", are described. The enzyme was isolated from erythrocytes of a patient with chronic non-spherocytic hemolytic anemia; in the blood cells 20% of the G6PD activity was maintained as compared with normal state. The partially purified enzyme was shown to be unstable in electrophoresis, it possessed a biphase type of pH-optima; Km value for NADP was decreased for glucose-6-phosphate Km value was normal. The thermostability of G6PD was normal at 46 within 1 hr."}
{"id": "PMID:17229", "title": "Drugs for peptic ulcer.", "content": "Conservative management of peptic ulcer relies on the use of drugs as an adjuvant to the time-honored measures of avoiding stress, reducing gastric secretion, and regulating the diet. Alkalies neutralize acid and anticholinergic drugs partly inhibit secretion.. Both are widely used but are often inadequate to control symptoms. Carbenoxolone appears to have a more specific effect in promoting healing of gastric ulcers and has now been used for 15 years. Its role in the treatment of gastric ulcer can be critrically examined, particularly in relation to how this influences surgical management. Recently introduced compounds know as histamine H2-receptor antagonists have a profound effect in inhibiting gastric secretion. Early experience in patients with duodenal ulcer indicated the efficacy of these compounds in promoting healing. These potent new drugs are likely to influence strongly the management of patients with duodenal ulcer, and this may affect the indications for surgery.", "contents": "Drugs for peptic ulcer. Conservative management of peptic ulcer relies on the use of drugs as an adjuvant to the time-honored measures of avoiding stress, reducing gastric secretion, and regulating the diet. Alkalies neutralize acid and anticholinergic drugs partly inhibit secretion.. Both are widely used but are often inadequate to control symptoms. Carbenoxolone appears to have a more specific effect in promoting healing of gastric ulcers and has now been used for 15 years. Its role in the treatment of gastric ulcer can be critrically examined, particularly in relation to how this influences surgical management. Recently introduced compounds know as histamine H2-receptor antagonists have a profound effect in inhibiting gastric secretion. Early experience in patients with duodenal ulcer indicated the efficacy of these compounds in promoting healing. These potent new drugs are likely to influence strongly the management of patients with duodenal ulcer, and this may affect the indications for surgery."}
{"id": "PMID:17225", "title": "[Degradation of polysomes of skeletal muscles of rats during preservation in solutions with different pH].", "content": "Alterations in properties of RNP-particles from rat sceletal muscles on storage of the preparations in buffer solutions at various pH were analyzed by means of centrifugation in sucrose gradients. Within 3 days of incubation at 20 the distribution of RNP-particles in the sucrose gradient was changed relatively slightly; which was due to the low activity of endogenous ribosomal RNAase. The fraction of the UV-absorbing material in polysomes was gradually decreased on storage and the fraction of subunits was increased respectively. The most distinct alterations were observed on incubation of the preparations at pH 6.0; the RNP-particles were apparently destructed after acidification of the medium.", "contents": "[Degradation of polysomes of skeletal muscles of rats during preservation in solutions with different pH]. Alterations in properties of RNP-particles from rat sceletal muscles on storage of the preparations in buffer solutions at various pH were analyzed by means of centrifugation in sucrose gradients. Within 3 days of incubation at 20 the distribution of RNP-particles in the sucrose gradient was changed relatively slightly; which was due to the low activity of endogenous ribosomal RNAase. The fraction of the UV-absorbing material in polysomes was gradually decreased on storage and the fraction of subunits was increased respectively. The most distinct alterations were observed on incubation of the preparations at pH 6.0; the RNP-particles were apparently destructed after acidification of the medium."}
{"id": "PMID:17224", "title": "[Inhibition of bacterial agmatinase by substrate analogs].", "content": "Activity of agmatinase (EC 3.5.3.11) from Proteus vulgaris was studied in presence of guanidine derivatives of agmatine as substrates. The guanidine derivatives, containing carboxyl group, did not interact with the enzyme. An inhibitory effect developed if the carboxyl group was esterified. For exhibition of the effect the length of hydrocarbon radical in ligand and presence of hydrophobic groups were important. One of the most effective inhibitor was N-isoamylene agmatine (K1=0.001 M). Compounds, containing an amino- or guanidine group at the position opposite to the guanidine end and possessing the hydrocarbon chain not less that C4 were shown to be substrates of agmatinase.", "contents": "[Inhibition of bacterial agmatinase by substrate analogs]. Activity of agmatinase (EC 3.5.3.11) from Proteus vulgaris was studied in presence of guanidine derivatives of agmatine as substrates. The guanidine derivatives, containing carboxyl group, did not interact with the enzyme. An inhibitory effect developed if the carboxyl group was esterified. For exhibition of the effect the length of hydrocarbon radical in ligand and presence of hydrophobic groups were important. One of the most effective inhibitor was N-isoamylene agmatine (K1=0.001 M). Compounds, containing an amino- or guanidine group at the position opposite to the guanidine end and possessing the hydrocarbon chain not less that C4 were shown to be substrates of agmatinase."}
{"id": "PMID:17230", "title": "Progress in the treatment of acute gastroduodenal mucosal lesions (AGML).", "content": "This article presents an analysis of acute gastroduodenal mucosal lesions (AGML) based on a review of current literature and the personal experience of the authors. The pathology of AGML involes two distinct types of lesions, namely, superficial erosions confined to the acid-secreting gastric mucosa and presenting as erosive hemorrhagic gastritis, and acute ulcers that occur in the alkaline gastric mucosa and duodenum. The etiology of these two lesions is very likely different. Acut gastroduodenal ulcers, best known as stress ulcers, are probably \"peptic\" lesions, whereas erosive hemorrhagic gastritis appears to be due to pathologic back diffusion of hydrogen ions caused by a breakdown of the gastric mucosal barrier as a result of endogenous factors, such as gastric mucosal ischemia, and sometimes exogenous factors, such as alcohol, urea, and acetylsalicylic acid. Catecholamine hypersecretion resulting from severe stress, such as occurs in hypovolemia, sepsis, and hypercapnea, contributes to ischemia of the gastric mucosa by producing splanchnic vasoconstriction. The key to the diagnosis of AGML is early endoscopy in all cases of upper gastrointestinal bleeding. Therapy for AGML should begin with a trial of medical measures directed at restoring effective perfusion of tissues and removing hydrogen ions from the stomach by gastric washing. Medical therapy is effective in 80% of patients with erosive hemorrhagic gastritis, but surgical treatment is usually required in acute gastroduodenal ulcer. When surgery is necessary for either type of lesion, vagotomy with hemigastrectomy appears to be the most effective operation. The personal experience of the authors has involved 36 patients with AGML who were treated in three periods between 1968 and 1976. The mortality rate of patients with AGML has been reduced from 50% in the first 2 years to zero in the last 2 years by the use of emergency endoscopy for diagnosis, appropriate medical therapy, properly timed and executed surgery, and, most recently, selective angiography.", "contents": "Progress in the treatment of acute gastroduodenal mucosal lesions (AGML). This article presents an analysis of acute gastroduodenal mucosal lesions (AGML) based on a review of current literature and the personal experience of the authors. The pathology of AGML involes two distinct types of lesions, namely, superficial erosions confined to the acid-secreting gastric mucosa and presenting as erosive hemorrhagic gastritis, and acute ulcers that occur in the alkaline gastric mucosa and duodenum. The etiology of these two lesions is very likely different. Acut gastroduodenal ulcers, best known as stress ulcers, are probably \"peptic\" lesions, whereas erosive hemorrhagic gastritis appears to be due to pathologic back diffusion of hydrogen ions caused by a breakdown of the gastric mucosal barrier as a result of endogenous factors, such as gastric mucosal ischemia, and sometimes exogenous factors, such as alcohol, urea, and acetylsalicylic acid. Catecholamine hypersecretion resulting from severe stress, such as occurs in hypovolemia, sepsis, and hypercapnea, contributes to ischemia of the gastric mucosa by producing splanchnic vasoconstriction. The key to the diagnosis of AGML is early endoscopy in all cases of upper gastrointestinal bleeding. Therapy for AGML should begin with a trial of medical measures directed at restoring effective perfusion of tissues and removing hydrogen ions from the stomach by gastric washing. Medical therapy is effective in 80% of patients with erosive hemorrhagic gastritis, but surgical treatment is usually required in acute gastroduodenal ulcer. When surgery is necessary for either type of lesion, vagotomy with hemigastrectomy appears to be the most effective operation. The personal experience of the authors has involved 36 patients with AGML who were treated in three periods between 1968 and 1976. The mortality rate of patients with AGML has been reduced from 50% in the first 2 years to zero in the last 2 years by the use of emergency endoscopy for diagnosis, appropriate medical therapy, properly timed and executed surgery, and, most recently, selective angiography."}
{"id": "PMID:17233", "title": "The effect of glucagon on pancreatic secretion and plasma secretin in dogs.", "content": "The inhibitory effect of glucagon on pancreatic exocrine secretion induced by endogenously released secretin was studied in 4 dogs with chronic pancreatic fistulas and open gastric fistulas. After a constant level of pancreatic secretion was established by intraduodenal hydrochloric acid perfusion (9 mEq/hr), glucagon (30 microng/kg-hr) was administered intravenously for 1 hr. Compared to a separate control study in which dogs received intraduodenal HC1 alone, glucagon caused a significant decrease in both pancreatic volume flow and bicarbonate output. Glucagon had no effect on pancreatic protein secretion, and circulating levels of endogenously released secretin remained unchanged. It is concluded that the inhibitory effect of glucagon on pancreatic secretion is not mediated through inhibition of secretin release. The chemical homology between glucagon and secretin suggests that glucagon may mediate its inhibitory action by competing with secretin at the level of the pancreatic receptor site.", "contents": "The effect of glucagon on pancreatic secretion and plasma secretin in dogs. The inhibitory effect of glucagon on pancreatic exocrine secretion induced by endogenously released secretin was studied in 4 dogs with chronic pancreatic fistulas and open gastric fistulas. After a constant level of pancreatic secretion was established by intraduodenal hydrochloric acid perfusion (9 mEq/hr), glucagon (30 microng/kg-hr) was administered intravenously for 1 hr. Compared to a separate control study in which dogs received intraduodenal HC1 alone, glucagon caused a significant decrease in both pancreatic volume flow and bicarbonate output. Glucagon had no effect on pancreatic protein secretion, and circulating levels of endogenously released secretin remained unchanged. It is concluded that the inhibitory effect of glucagon on pancreatic secretion is not mediated through inhibition of secretin release. The chemical homology between glucagon and secretin suggests that glucagon may mediate its inhibitory action by competing with secretin at the level of the pancreatic receptor site."}
{"id": "PMID:17249", "title": "Prevalence of drugs among drivers arrested for drinking and driving in Finland.", "content": "A combined thin layer and gas chromatography system was developed for qualitative and quantitative analysis of drugs in biological samples after extraction with heptane-isoamyl alcohol. Both acidic and basic extraction procedures were used. Special methods were used for the extraction and detection of salicylates, isoniazid, and morphine. Particular attention was given to the detection of psychostimulants; though these drugs have seldom been found in drinking drivers in Finland they are commonly found in Sweden. Two percent of all suspected drinking drivers were also suspected of concommitant drug use, which led to primary sampling of urine. Of 100 such drivers, 24 had blood alcohol levels (BALs) which were negative and 18 of that 24 had drugs in their sample. Seventy-six of the 100 had positive BALs and 25 of the 76 had drugs in their samples. Of the randomly chosen 100 suspected drinking drivers, 5 had drugs in their samples, and 4 of these 5 had positive BALs. The benzodiazeomes were the most commonly detected drugs. No stimulants were found in our subjects.", "contents": "Prevalence of drugs among drivers arrested for drinking and driving in Finland. A combined thin layer and gas chromatography system was developed for qualitative and quantitative analysis of drugs in biological samples after extraction with heptane-isoamyl alcohol. Both acidic and basic extraction procedures were used. Special methods were used for the extraction and detection of salicylates, isoniazid, and morphine. Particular attention was given to the detection of psychostimulants; though these drugs have seldom been found in drinking drivers in Finland they are commonly found in Sweden. Two percent of all suspected drinking drivers were also suspected of concommitant drug use, which led to primary sampling of urine. Of 100 such drivers, 24 had blood alcohol levels (BALs) which were negative and 18 of that 24 had drugs in their sample. Seventy-six of the 100 had positive BALs and 25 of the 76 had drugs in their samples. Of the randomly chosen 100 suspected drinking drivers, 5 had drugs in their samples, and 4 of these 5 had positive BALs. The benzodiazeomes were the most commonly detected drugs. No stimulants were found in our subjects."}
{"id": "PMID:17250", "title": "[Relationship between the characteristics of the acid stimulus and the impulse activity of medulla oblongata neurons in Cyprinus carpio carp].", "content": "In experiments on immobilized carps, by means of extracellular recordings, studies have been made of the neuronal activity of the facial lobe in the medulla evoked by stimulation of skin chemoreceptors of the mouth opening with hydrochloric and cytric acids. Responses of the neurons to these stimuli exhibit both similarities and differences. Composing across-neuron patterns, some aspects of coding of quality and intensity of chemical stimulus in fish were elucidated. Particularly it was shown that at low concentrations of acids, in neuronal coding of the stimuli the key role is played by qualitative peculiarities of the latter, but not by the level of pH.", "contents": "[Relationship between the characteristics of the acid stimulus and the impulse activity of medulla oblongata neurons in Cyprinus carpio carp]. In experiments on immobilized carps, by means of extracellular recordings, studies have been made of the neuronal activity of the facial lobe in the medulla evoked by stimulation of skin chemoreceptors of the mouth opening with hydrochloric and cytric acids. Responses of the neurons to these stimuli exhibit both similarities and differences. Composing across-neuron patterns, some aspects of coding of quality and intensity of chemical stimulus in fish were elucidated. Particularly it was shown that at low concentrations of acids, in neuronal coding of the stimuli the key role is played by qualitative peculiarities of the latter, but not by the level of pH."}
{"id": "PMID:17252", "title": "[Isolation and several properties of the glyceraldehyde-3-phosphate dehydrogenase from the muscles of the lamprey Lampetra fluviatillis].", "content": "Procedure for isolation of electrophoretically homogeneous, crystalline glyceraldehyde-3-phosphate dehydrogenase from lamprey muscles is described. Amino acid composition of the enzyme was investigated and compared with that of the same dehydrogenase from other sources. With respect to its secondary structure and kinetic parameters, the lamprey enzyme does not significantly differ from those of other animals. Activation energy for the lamprey enzyme is lower than for the same enzyme from endothermic animasl. \"Temperature modulation\" of Michaelis constant described in the literature, was not confirmed for the lamprey enzyme in the range of physiological pH values.", "contents": "[Isolation and several properties of the glyceraldehyde-3-phosphate dehydrogenase from the muscles of the lamprey Lampetra fluviatillis]. Procedure for isolation of electrophoretically homogeneous, crystalline glyceraldehyde-3-phosphate dehydrogenase from lamprey muscles is described. Amino acid composition of the enzyme was investigated and compared with that of the same dehydrogenase from other sources. With respect to its secondary structure and kinetic parameters, the lamprey enzyme does not significantly differ from those of other animals. Activation energy for the lamprey enzyme is lower than for the same enzyme from endothermic animasl. \"Temperature modulation\" of Michaelis constant described in the literature, was not confirmed for the lamprey enzyme in the range of physiological pH values."}
{"id": "PMID:17251", "title": "[Molecular evolution of glycogen phosphorylase and aminotransferases of vertebrate muscle tissue].", "content": "Comparative biochemical studies on phosphorylase b, aspartate aminotransferase and alanine aminotransferase in muscles of various vertebrates (the lamprey Lampetra fluviatilis, dogfish Squalus acanthias, rays Dasyatis pastinaca and Raja clavata, teleosts Scorpaena porcus, Spicara smaris, Esox lucius, Tinca tinca, Abramis brama, Lucioperca lucioperca, Cyprinus carpio, Salmo ischchan, frog Rana temporaria, tortoise Testudo horsfieldi) revealed some peculiarties of their molecular evolution. It was shown that isoenzyme PH-II, which comprises in most on the investigated lower vertebrates the main bulk of phosphorylase b, disappears in evolution of the type. Isoenzyme PH-I which is found in fisches in small amounts, increases in evolution becoming the sole form of phosphorylase b in skeletal muscles of endothermic animals. Mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase were found in all the vertebrates studied. Cytoplasmic isoenzyme from ectothermic and endothermic animals does not differ significantly, whereas the mitochondrial one undergoes considerable changes in the evolution of vertebrates.", "contents": "[Molecular evolution of glycogen phosphorylase and aminotransferases of vertebrate muscle tissue]. Comparative biochemical studies on phosphorylase b, aspartate aminotransferase and alanine aminotransferase in muscles of various vertebrates (the lamprey Lampetra fluviatilis, dogfish Squalus acanthias, rays Dasyatis pastinaca and Raja clavata, teleosts Scorpaena porcus, Spicara smaris, Esox lucius, Tinca tinca, Abramis brama, Lucioperca lucioperca, Cyprinus carpio, Salmo ischchan, frog Rana temporaria, tortoise Testudo horsfieldi) revealed some peculiarties of their molecular evolution. It was shown that isoenzyme PH-II, which comprises in most on the investigated lower vertebrates the main bulk of phosphorylase b, disappears in evolution of the type. Isoenzyme PH-I which is found in fisches in small amounts, increases in evolution becoming the sole form of phosphorylase b in skeletal muscles of endothermic animals. Mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase were found in all the vertebrates studied. Cytoplasmic isoenzyme from ectothermic and endothermic animals does not differ significantly, whereas the mitochondrial one undergoes considerable changes in the evolution of vertebrates."}
{"id": "PMID:17256", "title": "Purification and properties of L-asparaginase EC-2 from Escherichia coli 055:B5.", "content": "1. L-Asparaginase has been isolated from aerobically grown Escherichia coli 055:B5 and purified about 140-fold in a three-step procedure involving acidification to pH 4.5, ammonium sulphate fractionation and column chromatography on DEAE-Sephadex A-50. The activity of the preparation is 140 U/mg protein. 2. The enzyme acts within a broad pH range (pH 5-9) and is affected neither by PCMB, N-ethylmaleimide nor metal ions. 3. Molecular weight of the isolated asparaginase is 130 000.", "contents": "Purification and properties of L-asparaginase EC-2 from Escherichia coli 055:B5. 1. L-Asparaginase has been isolated from aerobically grown Escherichia coli 055:B5 and purified about 140-fold in a three-step procedure involving acidification to pH 4.5, ammonium sulphate fractionation and column chromatography on DEAE-Sephadex A-50. The activity of the preparation is 140 U/mg protein. 2. The enzyme acts within a broad pH range (pH 5-9) and is affected neither by PCMB, N-ethylmaleimide nor metal ions. 3. Molecular weight of the isolated asparaginase is 130 000."}
{"id": "PMID:17257", "title": "Increased serum prolactin in diabetic ketoacidosis; correlation between serum sodium and serum prolacting concentration.", "content": "In 8 patients with diabetic ketoacidosis, serum prolactin was measured and found to be elevated (24.8 +/- 10.2 ng/ml, mean +/- SEM). After correction of the ketoacidosis, the prolactin level decreased to 10.9 +/- 6.4 ng/ml (normal range men 4.9 +/-0.8, women 5.1 +/- 1.6 ng/ml). The scatter of prolactin values was wide. A study of the correlation between the serum prolactin values and chemical parameters that are altered in diabetic ketoacidosis was therefore undertaken. Serum prolactin values did not correlate well with the serum bicarbonate concentration or serum osmolality. However, a significant negative correlation between log serum prolactin concentration and serum sodium concentration was demonstrated (r = -0.61, P less than 0.01). It is suggested that serum prolactin may possible participate in sodium retention in man as has been demonstrated in studies on animals.", "contents": "Increased serum prolactin in diabetic ketoacidosis; correlation between serum sodium and serum prolacting concentration. In 8 patients with diabetic ketoacidosis, serum prolactin was measured and found to be elevated (24.8 +/- 10.2 ng/ml, mean +/- SEM). After correction of the ketoacidosis, the prolactin level decreased to 10.9 +/- 6.4 ng/ml (normal range men 4.9 +/-0.8, women 5.1 +/- 1.6 ng/ml). The scatter of prolactin values was wide. A study of the correlation between the serum prolactin values and chemical parameters that are altered in diabetic ketoacidosis was therefore undertaken. Serum prolactin values did not correlate well with the serum bicarbonate concentration or serum osmolality. However, a significant negative correlation between log serum prolactin concentration and serum sodium concentration was demonstrated (r = -0.61, P less than 0.01). It is suggested that serum prolactin may possible participate in sodium retention in man as has been demonstrated in studies on animals."}
{"id": "PMID:17258", "title": "Characterization of human ovarian oestradiol-17 beta oxidoreductase activity.", "content": "Oestradiol-17 beta oxidoreductase activity, which catalyzes the interconversion of oestrone and oestradiol, was investigated in preparations of human ovaries. The enzyme activities were localized primarily in the 105,000 X g supernatant fraction; dialyzed supernatant preparations were used in subsequent studies. The pH optima were 6.9 for reduction and 8.1 for 17 beta-dehydrogenation. The apparent Michaelis constants for oestrone and oestradiol were 1 X 10(-7) M and 5 X 10(-7) M, respectively. The enzyme activity was present with either NADP(H) or NAD(H), though (NADP(H) were the preferred cofactors. Non-aromatic steroids androstenedione, dehydroepiandrosterone, testosterone and 5-androstene-3beta,17beta-diol were poor substrates for the enzyme preparation. Methylation of the phenolic hydroxyl of oestrone and oestradiol resulted in slightly enhanced activities. The sulfhydryl reagent, N-ethylmaleimide, inhibited the reduction of oestrone. A dialyzed supernatant preparation retained approximately 79% of the original enzyme activity when stored at -20 degrees C for 6 weeks.", "contents": "Characterization of human ovarian oestradiol-17 beta oxidoreductase activity. Oestradiol-17 beta oxidoreductase activity, which catalyzes the interconversion of oestrone and oestradiol, was investigated in preparations of human ovaries. The enzyme activities were localized primarily in the 105,000 X g supernatant fraction; dialyzed supernatant preparations were used in subsequent studies. The pH optima were 6.9 for reduction and 8.1 for 17 beta-dehydrogenation. The apparent Michaelis constants for oestrone and oestradiol were 1 X 10(-7) M and 5 X 10(-7) M, respectively. The enzyme activity was present with either NADP(H) or NAD(H), though (NADP(H) were the preferred cofactors. Non-aromatic steroids androstenedione, dehydroepiandrosterone, testosterone and 5-androstene-3beta,17beta-diol were poor substrates for the enzyme preparation. Methylation of the phenolic hydroxyl of oestrone and oestradiol resulted in slightly enhanced activities. The sulfhydryl reagent, N-ethylmaleimide, inhibited the reduction of oestrone. A dialyzed supernatant preparation retained approximately 79% of the original enzyme activity when stored at -20 degrees C for 6 weeks."}
{"id": "PMID:17259", "title": "Pituitary LH and FSH and testosterone secretion in infants with undescended testes.", "content": "Twelve male infants with undescended testes (5 bilaterally, 7 unilaterally) were studied between the ages of 1 week and 11 months. As in older pre-pubertal cryptorchid boys, a significant decrease of the LH response to LH-RH test was found, while basal plasma levels of gonadotrophins and FSH response to LH-RH were normal. Plasma testosterone levels were in the normal range, and Leydig cells responded to stimulation by HCG, the degree of this response being significantly and positively correlated to the LH peak elicited by LH-RH. It may be concluded that some early defect of the pituitary-Leydig cell axis is associated with undescended testis.", "contents": "Pituitary LH and FSH and testosterone secretion in infants with undescended testes. Twelve male infants with undescended testes (5 bilaterally, 7 unilaterally) were studied between the ages of 1 week and 11 months. As in older pre-pubertal cryptorchid boys, a significant decrease of the LH response to LH-RH test was found, while basal plasma levels of gonadotrophins and FSH response to LH-RH were normal. Plasma testosterone levels were in the normal range, and Leydig cells responded to stimulation by HCG, the degree of this response being significantly and positively correlated to the LH peak elicited by LH-RH. It may be concluded that some early defect of the pituitary-Leydig cell axis is associated with undescended testis."}
{"id": "PMID:17262", "title": "Postoperative synovial fluid. Metabolic response to meniscectomy or synovectomy.", "content": "The metabolic response of synovial tissue to surgery was investigated by synovial fluid analysis after two types of operations, medial meniscectomy and synovectomy. Analyses of intra-articular fluid were also performed in non-operated patients with traumatic effusion or chronic synovitis in the knee. It was found that the knee joint metabolism in chronic synovitis is shifted towards anaerobic glycolysis in both operated and non-operated patients whereas meniscectomized and traumatized knees are more capable of maintaining oxidative metabolism. The data also demonstrate that one of the main reasons for decreased oxygen supply on the articular surface after meniscectomies or synovectomies is excessive intra-articular effusion which, according to earlier investigations, produces pressure in the joint cavity and inhibits local capillary circulation.", "contents": "Postoperative synovial fluid. Metabolic response to meniscectomy or synovectomy. The metabolic response of synovial tissue to surgery was investigated by synovial fluid analysis after two types of operations, medial meniscectomy and synovectomy. Analyses of intra-articular fluid were also performed in non-operated patients with traumatic effusion or chronic synovitis in the knee. It was found that the knee joint metabolism in chronic synovitis is shifted towards anaerobic glycolysis in both operated and non-operated patients whereas meniscectomized and traumatized knees are more capable of maintaining oxidative metabolism. The data also demonstrate that one of the main reasons for decreased oxygen supply on the articular surface after meniscectomies or synovectomies is excessive intra-articular effusion which, according to earlier investigations, produces pressure in the joint cavity and inhibits local capillary circulation."}
{"id": "PMID:17263", "title": "Infantile polyarteritis and Kawasaki disease.", "content": "Polyarteritis in infancy is very rare, difficult to diagnose and invariably fatal. A 6-month-old girl who presented with a prolonged unexplained fever and was subsequently demonstrated at post-mortem examination to have polyarteritis is described. The combination of polyarterits with some unusual presenting features suggests that the case described is one of the Mucocutaneous Lymph Node Syndrome (M.L.N.S.) or Kawasaki Disease. Polyarteritis and Kawasaki Disease are discussed with reference to the case described.", "contents": "Infantile polyarteritis and Kawasaki disease. Polyarteritis in infancy is very rare, difficult to diagnose and invariably fatal. A 6-month-old girl who presented with a prolonged unexplained fever and was subsequently demonstrated at post-mortem examination to have polyarteritis is described. The combination of polyarterits with some unusual presenting features suggests that the case described is one of the Mucocutaneous Lymph Node Syndrome (M.L.N.S.) or Kawasaki Disease. Polyarteritis and Kawasaki Disease are discussed with reference to the case described."}
{"id": "PMID:17267", "title": "[Behavior therapy and sex therapy].", "content": "The author attempts to situate sextherapy of Masters and Johnson in relation to behaviour therapy in indicating the principles elaborated by old behaviour therapy and its most recent developments which are at the origin of sextherapy. He also considers the problem of indications and complementary relation which can be comprehended between these approaches and the psychoanalytical approach.", "contents": "[Behavior therapy and sex therapy]. The author attempts to situate sextherapy of Masters and Johnson in relation to behaviour therapy in indicating the principles elaborated by old behaviour therapy and its most recent developments which are at the origin of sextherapy. He also considers the problem of indications and complementary relation which can be comprehended between these approaches and the psychoanalytical approach."}
{"id": "PMID:17268", "title": "Hyperthermic tumour-cell devitalization in vivo.", "content": "A review of the morphologic, biochemical and clinical effects of hyperthermia on malignant cells indicates the presence of two principally different heat-induced alterations. (1) A 'destructive' lysosomal dependent cytoplasmic reaction dominates the tumour-cell devitalization in vivo, probably influenced by the characteristic tumour cell environment. (2) 'Repressive' nuclear abnormalities may be observed, but seem to be secondary in the in vivo reaction. However, under certain conditions (combined treatment modalities) this nuclear effect may be of importance.", "contents": "Hyperthermic tumour-cell devitalization in vivo. A review of the morphologic, biochemical and clinical effects of hyperthermia on malignant cells indicates the presence of two principally different heat-induced alterations. (1) A 'destructive' lysosomal dependent cytoplasmic reaction dominates the tumour-cell devitalization in vivo, probably influenced by the characteristic tumour cell environment. (2) 'Repressive' nuclear abnormalities may be observed, but seem to be secondary in the in vivo reaction. However, under certain conditions (combined treatment modalities) this nuclear effect may be of importance."}
{"id": "PMID:17264", "title": "Acid base equilibrium in experimental acidosis of cows with and without rumen fistula.", "content": "Acid base equilibrium in experimental acidosis of cows with and without rumen fistula. Acta Physiol. Pol., 1977, 28, (1): 77-84. Symptoms of acidosis caused by administration of saccharose into the rumen were more significant and lasted longer in the cows without rumen fistula than in those with it. At the peak of acidosis of pH of arterial blood was 7.29 and it was by 0.07 below that in the group of cows with fistula. The alkali reserve was lower by 6 mEq and the bicarbonate level by 5.2. Characteristic differences were observed in oxygen utilization and nitrogen metabolism. Thus, the results obtained in experiments on the cows with rumen fistula do not reflect the normal metabolic processes.", "contents": "Acid base equilibrium in experimental acidosis of cows with and without rumen fistula. Acid base equilibrium in experimental acidosis of cows with and without rumen fistula. Acta Physiol. Pol., 1977, 28, (1): 77-84. Symptoms of acidosis caused by administration of saccharose into the rumen were more significant and lasted longer in the cows without rumen fistula than in those with it. At the peak of acidosis of pH of arterial blood was 7.29 and it was by 0.07 below that in the group of cows with fistula. The alkali reserve was lower by 6 mEq and the bicarbonate level by 5.2. Characteristic differences were observed in oxygen utilization and nitrogen metabolism. Thus, the results obtained in experiments on the cows with rumen fistula do not reflect the normal metabolic processes."}
{"id": "PMID:17269", "title": "Photolysis of desmosine and isodesmosine by ultraviolet light.", "content": "It is known that the pyridinium ring of a model compound such as N-methyl pyridinium chloride is cleaved by U.V. radiation at 254 nm. At acid pH the products obtained are methylamine and glutaconaldehyde. Under the same conditions desmosine and isodesmosine are degraded into lysine and probably into the homologous substituted ketone of glutaconaldehyde. At pH 6.0-7.0, a transient open-chain aminoaldehyde intermediate is observed which can either reform the original compound or be cleaved as at low pH. When intact elastin is photolysed for 20 minutes in water, approximately 75% of the (iso) desmosines are destroyed, accompanied by an increase of free lysine residues. No change in the concentration of the other amino acids, including tyrosine, are noted. It is therefore likely that the crosslinks engaged in peptide links are also cleaved photochemically.", "contents": "Photolysis of desmosine and isodesmosine by ultraviolet light. It is known that the pyridinium ring of a model compound such as N-methyl pyridinium chloride is cleaved by U.V. radiation at 254 nm. At acid pH the products obtained are methylamine and glutaconaldehyde. Under the same conditions desmosine and isodesmosine are degraded into lysine and probably into the homologous substituted ketone of glutaconaldehyde. At pH 6.0-7.0, a transient open-chain aminoaldehyde intermediate is observed which can either reform the original compound or be cleaved as at low pH. When intact elastin is photolysed for 20 minutes in water, approximately 75% of the (iso) desmosines are destroyed, accompanied by an increase of free lysine residues. No change in the concentration of the other amino acids, including tyrosine, are noted. It is therefore likely that the crosslinks engaged in peptide links are also cleaved photochemically."}
{"id": "PMID:17265", "title": "The influence of histamine on metabolism of dopamine and serotonin in the rat striatum.", "content": "The influence of histamine on metabolism of dopamine and serotonin in the rat striatum. Acta Physiol. Pol., 1977, 28 (2): 101--105. Histamine-2HC1 (Hi) given in a dose of 500 micron g did not change DA level in the striatum but HVA was increased by approx. 50%. The Hi-induced rise of HVA level was prevented in animals pretreated with an antihistaminic drug--mepyramine. The pretreatment of rats with atropine reduced significantly the Hi-induced rise of HVA concentration. Hi did not significantly influence 5-HT content in the striatum while the level of 5-HIAA was simultaneously increased by 15%. It is concluded that Hi-induced elevation of HVA content is not a direct effect of Hi on dopaminergic neurons but the Hi action is exerted indirectly through cholinergic system. The increase of serotoninergic activity is probably a consequence of an increased activity of dopaminergic neurons in the striatum.", "contents": "The influence of histamine on metabolism of dopamine and serotonin in the rat striatum. The influence of histamine on metabolism of dopamine and serotonin in the rat striatum. Acta Physiol. Pol., 1977, 28 (2): 101--105. Histamine-2HC1 (Hi) given in a dose of 500 micron g did not change DA level in the striatum but HVA was increased by approx. 50%. The Hi-induced rise of HVA level was prevented in animals pretreated with an antihistaminic drug--mepyramine. The pretreatment of rats with atropine reduced significantly the Hi-induced rise of HVA concentration. Hi did not significantly influence 5-HT content in the striatum while the level of 5-HIAA was simultaneously increased by 15%. It is concluded that Hi-induced elevation of HVA content is not a direct effect of Hi on dopaminergic neurons but the Hi action is exerted indirectly through cholinergic system. The increase of serotoninergic activity is probably a consequence of an increased activity of dopaminergic neurons in the striatum."}
{"id": "PMID:17272", "title": "Studies on lysyl oxidase of bovine ligamentum nuchae and bovine aorta.", "content": "Lysyl oxidase had been purified to near homogeneity from bovine aorta and bovine ligamentum nuchae employing a modification of methods described by Harris et al., and Stassen and his colleagues. The aortic enzyme gives rise to at least three peaks and the ligament enzyme resolves into at least four peaks upon chromatography on DEAE cellulose. The molecular weight of each peak of both enzymes is approximately 30,000 daltons in sodium dodecyl sulfate. The aortic enzyme aggregates to species with molecular weights varying from approximately 60,000 to 1,000,000 daltons upon dialysis out of urea into phosphate-buffered saline. Temperature studies reveal that lysyl oxidase is stable to temperatures as high as 80 degrees C, although the assay optimum is 52 degrees C. Studies in progress suggest the temperature dependency of assay may reflect conformational changes in the elastin substrate.", "contents": "Studies on lysyl oxidase of bovine ligamentum nuchae and bovine aorta. Lysyl oxidase had been purified to near homogeneity from bovine aorta and bovine ligamentum nuchae employing a modification of methods described by Harris et al., and Stassen and his colleagues. The aortic enzyme gives rise to at least three peaks and the ligament enzyme resolves into at least four peaks upon chromatography on DEAE cellulose. The molecular weight of each peak of both enzymes is approximately 30,000 daltons in sodium dodecyl sulfate. The aortic enzyme aggregates to species with molecular weights varying from approximately 60,000 to 1,000,000 daltons upon dialysis out of urea into phosphate-buffered saline. Temperature studies reveal that lysyl oxidase is stable to temperatures as high as 80 degrees C, although the assay optimum is 52 degrees C. Studies in progress suggest the temperature dependency of assay may reflect conformational changes in the elastin substrate."}
{"id": "PMID:17274", "title": "The coacervate-sol transition observed with alpha-elastin and its N-formyl O-methyl derivative.", "content": "The coacervate phase produced by raising the temperature of solutions of blocked alpha-elastin has water content and fibrillar structure at electron microscope level similar to fibrous elastin (Cox, B.A., Starcher, B.C., Urry, D.W. (1973) Biochim, Biophys. Acta 317, 209-213). The stability ranges of the coacervates under varying conditions of temperature, pH, salt concentration and concentration of added organic solvent have been investigated with results that suggest a marked sensitivity of elastin conformation to solution conditions.", "contents": "The coacervate-sol transition observed with alpha-elastin and its N-formyl O-methyl derivative. The coacervate phase produced by raising the temperature of solutions of blocked alpha-elastin has water content and fibrillar structure at electron microscope level similar to fibrous elastin (Cox, B.A., Starcher, B.C., Urry, D.W. (1973) Biochim, Biophys. Acta 317, 209-213). The stability ranges of the coacervates under varying conditions of temperature, pH, salt concentration and concentration of added organic solvent have been investigated with results that suggest a marked sensitivity of elastin conformation to solution conditions."}
{"id": "PMID:17277", "title": "Purification of vaccinia virus by zonal centrifugation and analysis of viral protein composition.", "content": "Vaccinia virus propagated in rotated cultures of RK13 cells was purified by sucrose density gradient zonal centrifugation. The purified virus was dissociated with sodium dodecyl sulfate end its protein composition analyzed by polyacrylamide gel electrophoresis. The protein composition of the virion envelope, isolated by the non-ionic detergent Nonidet P-40, was also determined.", "contents": "Purification of vaccinia virus by zonal centrifugation and analysis of viral protein composition. Vaccinia virus propagated in rotated cultures of RK13 cells was purified by sucrose density gradient zonal centrifugation. The purified virus was dissociated with sodium dodecyl sulfate end its protein composition analyzed by polyacrylamide gel electrophoresis. The protein composition of the virion envelope, isolated by the non-ionic detergent Nonidet P-40, was also determined."}
{"id": "PMID:17278", "title": "Effect of influenza virus on the immune responsiveness of animals.", "content": "Infection of mice with A/Hong Kong/1/68 (H3N2) and A/PR8/34 (H0N1) influenza virus strains resulted in a significant inhibition of the formation of antibody-producing cells in response to administration of sheep erythrocytes and a reduced capacity of spleen cells to induce \"graft-versus-host\" reaction. The immunosuppression caused by influenza infection was observed for a long period of time post infection (3--6 months). The extent of inhibition of antibody production depended on the dose of virus, route of inoculation, the sequence of infection and immunization and the internal between them. Heat-inactivated virus exerted no immunosuppressive effect.", "contents": "Effect of influenza virus on the immune responsiveness of animals. Infection of mice with A/Hong Kong/1/68 (H3N2) and A/PR8/34 (H0N1) influenza virus strains resulted in a significant inhibition of the formation of antibody-producing cells in response to administration of sheep erythrocytes and a reduced capacity of spleen cells to induce \"graft-versus-host\" reaction. The immunosuppression caused by influenza infection was observed for a long period of time post infection (3--6 months). The extent of inhibition of antibody production depended on the dose of virus, route of inoculation, the sequence of infection and immunization and the internal between them. Heat-inactivated virus exerted no immunosuppressive effect."}
{"id": "PMID:17279", "title": "Effects of tilorone hydrochloride on experimental flavivirus infections in mice.", "content": "The effect of tilorone hydrochloride on experimental infections of mice with West Nile, Langat and Dengue type 2 viruses were studied. The drug significantly reduced the mortality after intraperitoneal inoculation of West Nile virus, but failed to affect intracerebral infection with Langat or Dengue viruses. Tilorone partially reversed cyclophosphan-enhanced mortality after extraneural inoculation of West Nile and Langat viruses. The possible modes of action of tilorone, interferon-inducing ability and stimulation of humoral immunity, are discussed.", "contents": "Effects of tilorone hydrochloride on experimental flavivirus infections in mice. The effect of tilorone hydrochloride on experimental infections of mice with West Nile, Langat and Dengue type 2 viruses were studied. The drug significantly reduced the mortality after intraperitoneal inoculation of West Nile virus, but failed to affect intracerebral infection with Langat or Dengue viruses. Tilorone partially reversed cyclophosphan-enhanced mortality after extraneural inoculation of West Nile and Langat viruses. The possible modes of action of tilorone, interferon-inducing ability and stimulation of humoral immunity, are discussed."}
{"id": "PMID:17280", "title": "Experimental Hazara Virus infection in mice.", "content": "Reproduction of Hazara virus in intracerebrally (ic) inoculated newborn white mice was studied by virological, serological and histological methods, electron microscopy and the direct fluorescent antibody technique. In the course of infection the virus was detectable in the blood, brain and some viscera, the largest amounts of virus occurring in the brain and liver. Pathomorphological lesions were localized in the brain and consisted of foci of neuronal destruction and marked oedema of the tissue. Electron microscopy of ultrathin sections of tissues from various parts of brains of infected newborn white mice killed at the height of infection revealed virus particles in perikaryon of the brain cortex neurons; accumulations of particles were found in vesicles of the Golgi complex and the endoplasmic reticulum.", "contents": "Experimental Hazara Virus infection in mice. Reproduction of Hazara virus in intracerebrally (ic) inoculated newborn white mice was studied by virological, serological and histological methods, electron microscopy and the direct fluorescent antibody technique. In the course of infection the virus was detectable in the blood, brain and some viscera, the largest amounts of virus occurring in the brain and liver. Pathomorphological lesions were localized in the brain and consisted of foci of neuronal destruction and marked oedema of the tissue. Electron microscopy of ultrathin sections of tissues from various parts of brains of infected newborn white mice killed at the height of infection revealed virus particles in perikaryon of the brain cortex neurons; accumulations of particles were found in vesicles of the Golgi complex and the endoplasmic reticulum."}
{"id": "PMID:17281", "title": "Susceptibility of laboratory and domestic animals to experimental infection with Orungo virus.", "content": "Laboratory and domestic animals: mice, hamsters, rabbits, sparrows, chickens and lambs were inoculated with Orungo virus to determine their susceptibility as evidenced by clinical response, viraemia and antibody development. Mice and hamsters circulated the virus and developed neutralising antibodies; clinical signs of disease included ruffled hair coat, hypersensitivity to sudden noise and hindleg paralysis. There was an age-related susceptibility to infection in these two animals. Rabbits and lambs developed neutralising antibody but not viraemia, nor did they show signs of illness. Sparrows and chickens neither circulated the virus, nor developed neutralising antibodies to Orungo virus.", "contents": "Susceptibility of laboratory and domestic animals to experimental infection with Orungo virus. Laboratory and domestic animals: mice, hamsters, rabbits, sparrows, chickens and lambs were inoculated with Orungo virus to determine their susceptibility as evidenced by clinical response, viraemia and antibody development. Mice and hamsters circulated the virus and developed neutralising antibodies; clinical signs of disease included ruffled hair coat, hypersensitivity to sudden noise and hindleg paralysis. There was an age-related susceptibility to infection in these two animals. Rabbits and lambs developed neutralising antibody but not viraemia, nor did they show signs of illness. Sparrows and chickens neither circulated the virus, nor developed neutralising antibodies to Orungo virus."}
{"id": "PMID:17283", "title": "The antiviral activity of dipyridamole.", "content": "Dipyridamole, a coronary vasodilatator, was found to possess antiviral activity against representatives of different families. The antiviral properties were studied in chick embryo, human diplid and FL cell cultures by the agar diffusion plaque inhibition and plaque reduction tests and one-step growth cycle experiments. The inhibition of the virus-induced cytopathic effect was estimated quantitatively. Dipyridamole significantly inhibited the yield of members of the viral families Picornaviridae, Togaviridae, Orthomyxoviridae, Paramyxoviridae, Herpetoviridae and Poxviridae, as well as of Chlamydiaceae (sheep abortion agent).", "contents": "The antiviral activity of dipyridamole. Dipyridamole, a coronary vasodilatator, was found to possess antiviral activity against representatives of different families. The antiviral properties were studied in chick embryo, human diplid and FL cell cultures by the agar diffusion plaque inhibition and plaque reduction tests and one-step growth cycle experiments. The inhibition of the virus-induced cytopathic effect was estimated quantitatively. Dipyridamole significantly inhibited the yield of members of the viral families Picornaviridae, Togaviridae, Orthomyxoviridae, Paramyxoviridae, Herpetoviridae and Poxviridae, as well as of Chlamydiaceae (sheep abortion agent)."}
{"id": "PMID:17284", "title": "Enzymatic activity of blood lymphocytes experimental tsutsugamushi fever in mice.", "content": "The influence of tsutsugamushi fever infection on the metabolism of blood lymphocytes of mice differing in susceptibility to Rickettsia tsutsugamushi and of rifampicine and tetracycline treatment was studied. In susceptible mice, the activity of oxidation-reduction processes in lymphocytes increased at 7--10 days of the disease and became normal upon recovery of the animals. In mice with low susceptibility this increase of the activity began and terminated much earlier, at 3--5 days. Treatment of the infection with antibiotics resulted in a rapid arrest of the disease and normalization of the lymphocyte activity. The relationship between susceptibility of the animals to R. tsutsugamushi and the activity of oxidation-reduction enzymes is discussed on the example of succinate dehydrogenase.", "contents": "Enzymatic activity of blood lymphocytes experimental tsutsugamushi fever in mice. The influence of tsutsugamushi fever infection on the metabolism of blood lymphocytes of mice differing in susceptibility to Rickettsia tsutsugamushi and of rifampicine and tetracycline treatment was studied. In susceptible mice, the activity of oxidation-reduction processes in lymphocytes increased at 7--10 days of the disease and became normal upon recovery of the animals. In mice with low susceptibility this increase of the activity began and terminated much earlier, at 3--5 days. Treatment of the infection with antibiotics resulted in a rapid arrest of the disease and normalization of the lymphocyte activity. The relationship between susceptibility of the animals to R. tsutsugamushi and the activity of oxidation-reduction enzymes is discussed on the example of succinate dehydrogenase."}
{"id": "PMID:17285", "title": "Purification of free polyhedrosis virus infecting Galleria mellonella L.", "content": "Free Galleria mellonella nuclear polyhedrosis virus was purified 4000--4500 times by Tween-80 treatment and repeated sucrose density gradient centrifugation, based on the ratio of infectivity to protein content as compared to the starting virus-containing suspension.", "contents": "Purification of free polyhedrosis virus infecting Galleria mellonella L. Free Galleria mellonella nuclear polyhedrosis virus was purified 4000--4500 times by Tween-80 treatment and repeated sucrose density gradient centrifugation, based on the ratio of infectivity to protein content as compared to the starting virus-containing suspension."}
{"id": "PMID:17286", "title": "Biological characteristic of Nigerian strains of West Nile virus in mice and cell cultures.", "content": "The biological characteristic in mice and cell cultures of 7 strains of West Nile (WN) virus isolated in Nigeria were studied. The pattern of virus development in most organs of mice infected with two of the seven strains tested was identical, while it varied with the remaining five strains. All 7 strains of WN virus multiplied with a cytopathic effect (CPE) in the four cell cultures examined.", "contents": "Biological characteristic of Nigerian strains of West Nile virus in mice and cell cultures. The biological characteristic in mice and cell cultures of 7 strains of West Nile (WN) virus isolated in Nigeria were studied. The pattern of virus development in most organs of mice infected with two of the seven strains tested was identical, while it varied with the remaining five strains. All 7 strains of WN virus multiplied with a cytopathic effect (CPE) in the four cell cultures examined."}
{"id": "PMID:17287", "title": "Serotyping of coxsackieviruses by immune electron microscopy.", "content": "Coxsackieviruses B1, B2 and B3 were identified by immune electron microscopy. The results were in good agreement with those of virus neutralization tests in cell cultures.", "contents": "Serotyping of coxsackieviruses by immune electron microscopy. Coxsackieviruses B1, B2 and B3 were identified by immune electron microscopy. The results were in good agreement with those of virus neutralization tests in cell cultures."}
{"id": "PMID:17288", "title": "Plaque formation by alphavirus (Getah) in Culex Mosquito cells.", "content": "Plaques were formed by Getah virus (an Alphavirus) which had been grown in BHK cells and passaged once in Culex cells before inoculation of Culex cell cultures. Plaques were not produced either by Getah or Japanese encephalitis (JE) viruses which had been passaged only in BHK cells. Plaque counts in Culex cell monolayers were almost the same as in BHK cells.", "contents": "Plaque formation by alphavirus (Getah) in Culex Mosquito cells. Plaques were formed by Getah virus (an Alphavirus) which had been grown in BHK cells and passaged once in Culex cells before inoculation of Culex cell cultures. Plaques were not produced either by Getah or Japanese encephalitis (JE) viruses which had been passaged only in BHK cells. Plaque counts in Culex cell monolayers were almost the same as in BHK cells."}
{"id": "PMID:17289", "title": "Role of normal cell antigens in the establishment of measles virus in newborn white mice.", "content": "The Edmontson strain of measles virus was adapted to the brains of newborn white mice to which extracts from African green monkey kidney (Vero) cells used for maintenance of measles virus had been injected intracerebrally. The animals showed symptoms of involvement of the central nervous system (pareses, paralyses) which reappeared in subsequent passages.", "contents": "Role of normal cell antigens in the establishment of measles virus in newborn white mice. The Edmontson strain of measles virus was adapted to the brains of newborn white mice to which extracts from African green monkey kidney (Vero) cells used for maintenance of measles virus had been injected intracerebrally. The animals showed symptoms of involvement of the central nervous system (pareses, paralyses) which reappeared in subsequent passages."}
{"id": "PMID:17292", "title": "Interaction of plasma membranes with influenza virus. VII. Effect on 3',5'-cyclic adenosine monophosphate phosphodiesterase activity.", "content": "In chick embryo cells (CEC) and plasma membranes (PM) isolated therefrom, three forms of 3',5'-cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) were demonstrated: (1) PDE activated only by Ca2+ (Ca-PDE); (2) PDE activated only by Mg2+ (Mg-PDE); and (3) PDE stimulated in the presence of 2 mM Mg2+ by low concentrations of Ca2+ (Ca-Mg-PDE). Purified influenza A virus, under suitable conditions, lowered the activities of these PDEs. The decrease was greater in samples incubated in the presence of adenosine triphosphate (ATP) than in those incubated in its absence.", "contents": "Interaction of plasma membranes with influenza virus. VII. Effect on 3',5'-cyclic adenosine monophosphate phosphodiesterase activity. In chick embryo cells (CEC) and plasma membranes (PM) isolated therefrom, three forms of 3',5'-cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) were demonstrated: (1) PDE activated only by Ca2+ (Ca-PDE); (2) PDE activated only by Mg2+ (Mg-PDE); and (3) PDE stimulated in the presence of 2 mM Mg2+ by low concentrations of Ca2+ (Ca-Mg-PDE). Purified influenza A virus, under suitable conditions, lowered the activities of these PDEs. The decrease was greater in samples incubated in the presence of adenosine triphosphate (ATP) than in those incubated in its absence."}
{"id": "PMID:17294", "title": "Reduced renal acid excretion in malnutrition: a result of phosphate depletion.", "content": "Eleven infants recovering from protein-calorie malnutrition secondary to acquired monosaccharide intolerance were found to have reduced plasma bicarbonate concentration associated with inadequate weight gain. Renal net acid excretion (NAE) was decreased to a mean of 34.2 micronEq/1.73m2/min. Titratable acidity (TA) was markedly reduced, accounting for only 16% of NAE. This marked reduction in TA was associated with reduced mean phosphate (PO4) excretion (.074 mg/min) and a reduced mean serum PO4 (3.9 mg/dl), suggesting PO4 depletion. Two patients received intravenous phosphate loads, resulting in an increase in mean NAE from 35.1 to 89.7 microgEq/1.73m2/min. A similar response was seen after oral PO4 supplementation. Three patients were studied after partial correction of their acidosis. At a relatively low plasma bicarbonate concentration (mean = 16.6 mmoles/liter) significant amounts of bicarbonate were detected in the urine (mean = 8.7 micronEq/1.73m2/min), suggesting a defect in bicarbonate reabsorption. Five patients studied after complete recovery from malnutrition had normal NAE in response to ammonium chloride load. The reduction in NAE appears to be secondary to unavailability of urinary buffers and a reduction in bicarbonate reabsorption; both of these defects can be explained by phosphate depletion.", "contents": "Reduced renal acid excretion in malnutrition: a result of phosphate depletion. Eleven infants recovering from protein-calorie malnutrition secondary to acquired monosaccharide intolerance were found to have reduced plasma bicarbonate concentration associated with inadequate weight gain. Renal net acid excretion (NAE) was decreased to a mean of 34.2 micronEq/1.73m2/min. Titratable acidity (TA) was markedly reduced, accounting for only 16% of NAE. This marked reduction in TA was associated with reduced mean phosphate (PO4) excretion (.074 mg/min) and a reduced mean serum PO4 (3.9 mg/dl), suggesting PO4 depletion. Two patients received intravenous phosphate loads, resulting in an increase in mean NAE from 35.1 to 89.7 microgEq/1.73m2/min. A similar response was seen after oral PO4 supplementation. Three patients were studied after partial correction of their acidosis. At a relatively low plasma bicarbonate concentration (mean = 16.6 mmoles/liter) significant amounts of bicarbonate were detected in the urine (mean = 8.7 micronEq/1.73m2/min), suggesting a defect in bicarbonate reabsorption. Five patients studied after complete recovery from malnutrition had normal NAE in response to ammonium chloride load. The reduction in NAE appears to be secondary to unavailability of urinary buffers and a reduction in bicarbonate reabsorption; both of these defects can be explained by phosphate depletion."}
{"id": "PMID:17295", "title": "Contribution of arterial blood lactate measurement to the care of critically ill patients.", "content": "Arterial blood samples from 202 critically ill patients were studied. Lactate concentration, PO2, PCO2, pH, oxygen saturation, total CO2, and toe temperature were measured. Base excess, buffer base, actual bicarbonate, and standard bicarbonate were calculated. Analysis of the initial data obtained from each patient revealed that lactate concentration alone could not be used to predict survival. Elevations in lactate concentrations were observed in all types of acid-base disturbances. Survival was lowest (30%) for patients in metabolic acidosis with respiratory compensation, mean lactate concentration 10.5 mEq/l (mmol/l), and highest (65%) for patients in uncompensated respiratory alkalosis, mean lactate concentration, 2.57 mEq/l (mmol/l). Knowing the type of acid-base disturbance is necessary to evaluate the significance of elevated blood lactate values.", "contents": "Contribution of arterial blood lactate measurement to the care of critically ill patients. Arterial blood samples from 202 critically ill patients were studied. Lactate concentration, PO2, PCO2, pH, oxygen saturation, total CO2, and toe temperature were measured. Base excess, buffer base, actual bicarbonate, and standard bicarbonate were calculated. Analysis of the initial data obtained from each patient revealed that lactate concentration alone could not be used to predict survival. Elevations in lactate concentrations were observed in all types of acid-base disturbances. Survival was lowest (30%) for patients in metabolic acidosis with respiratory compensation, mean lactate concentration 10.5 mEq/l (mmol/l), and highest (65%) for patients in uncompensated respiratory alkalosis, mean lactate concentration, 2.57 mEq/l (mmol/l). Knowing the type of acid-base disturbance is necessary to evaluate the significance of elevated blood lactate values."}
{"id": "PMID:17297", "title": "The pediatric practice of the child health associate.", "content": "Child health associates are individuals who have completed the three-year Child Health Associate Program at the University of Colorado School of Medicine and are certified by the Colorado State Board of Medical Examiners to practice pediatrics under physician supervision. To our knowledge, this study is the first to describe the practice profile of child health associates. We found them able to provide health care services without direct physician assistance to 91.4% (2,160 of 2,363) of pediatric patients in ambulatory settings. They saw the same variety of patients as primary physicians and identified a broad range of common pediatric problems. Each supervising physician spent an average time of 5.9 minutes with the child health associate in evaluating the 8.6% of patients who required consultation. The child health associate is fully able to serve as a primary health care practitioner for children.", "contents": "The pediatric practice of the child health associate. Child health associates are individuals who have completed the three-year Child Health Associate Program at the University of Colorado School of Medicine and are certified by the Colorado State Board of Medical Examiners to practice pediatrics under physician supervision. To our knowledge, this study is the first to describe the practice profile of child health associates. We found them able to provide health care services without direct physician assistance to 91.4% (2,160 of 2,363) of pediatric patients in ambulatory settings. They saw the same variety of patients as primary physicians and identified a broad range of common pediatric problems. Each supervising physician spent an average time of 5.9 minutes with the child health associate in evaluating the 8.6% of patients who required consultation. The child health associate is fully able to serve as a primary health care practitioner for children."}
{"id": "PMID:17298", "title": "Immunologic studies and clinical follow-up HBsAg-positive polyarteritis nodosa.", "content": "Three patients with hepatitis B surface antigen (HBsAg)-positive polyarteritis nodosa (PAN) who are clinically well 4 1/2-5 1/2 years after their initial illnesses are described. In each case electron microscopic studies demonstrated the presence of aggregates of HBsAg in both acute and quiescent phase sera. One patient had a lower circulating HBsAg titer during the acute illness, while no change in serial HBsAg titers was observed in the other two patients. Two of the three patients showed lymphocyte transformation to purified HBsAg during the quiescent phase of the PAN. The role of immune complexes in the pathogenesis of HBsAg-positive PAN is discussed.", "contents": "Immunologic studies and clinical follow-up HBsAg-positive polyarteritis nodosa. Three patients with hepatitis B surface antigen (HBsAg)-positive polyarteritis nodosa (PAN) who are clinically well 4 1/2-5 1/2 years after their initial illnesses are described. In each case electron microscopic studies demonstrated the presence of aggregates of HBsAg in both acute and quiescent phase sera. One patient had a lower circulating HBsAg titer during the acute illness, while no change in serial HBsAg titers was observed in the other two patients. Two of the three patients showed lymphocyte transformation to purified HBsAg during the quiescent phase of the PAN. The role of immune complexes in the pathogenesis of HBsAg-positive PAN is discussed."}
{"id": "PMID:17299", "title": "Idiopathic proctitis. I. The morphology of proximal colonic mucosa and its clinical significance.", "content": "A group of 31 patients with idiopathic proctitis were colonoscoped while they were symptomatic. Multiple mucosal biopsies were taken from the transverse, descending, and sigmoid colon and from the rectum. While visualization by colonoscopy revealed abnormalities limited to the most distal 18-20 cm of the colon, microscopic abnormalities were frequently seen in more proximal locations. Analysis of clinicopathological data indicates that there is good correlation between the extent of microscopic mucosal abnormalities and the clinical course. Patients with abnormalities limited to the rectum generally responded well to conventional treatment while patients with more proximal involvement were refractory to such therapy.", "contents": "Idiopathic proctitis. I. The morphology of proximal colonic mucosa and its clinical significance. A group of 31 patients with idiopathic proctitis were colonoscoped while they were symptomatic. Multiple mucosal biopsies were taken from the transverse, descending, and sigmoid colon and from the rectum. While visualization by colonoscopy revealed abnormalities limited to the most distal 18-20 cm of the colon, microscopic abnormalities were frequently seen in more proximal locations. Analysis of clinicopathological data indicates that there is good correlation between the extent of microscopic mucosal abnormalities and the clinical course. Patients with abnormalities limited to the rectum generally responded well to conventional treatment while patients with more proximal involvement were refractory to such therapy."}
{"id": "PMID:17301", "title": "Low-dose methazolamide and intraocular pressure.", "content": "Sixteen patients with increased intraocular pressure (over 20 mm Hg) received 25 and 50 mg of oral methazolamide, twice daily, during consecutive weeks and then 500 mg (Sequels) of acetazolamide. The two methazolamide regimens produced significant decreases in intraocular pressure. Acetazolamide treatment resulted in a greater decrease in intraocular pressure but more systemic acidosis and side effects.", "contents": "Low-dose methazolamide and intraocular pressure. Sixteen patients with increased intraocular pressure (over 20 mm Hg) received 25 and 50 mg of oral methazolamide, twice daily, during consecutive weeks and then 500 mg (Sequels) of acetazolamide. The two methazolamide regimens produced significant decreases in intraocular pressure. Acetazolamide treatment resulted in a greater decrease in intraocular pressure but more systemic acidosis and side effects."}
{"id": "PMID:17302", "title": "Clinical implications of benzodiazepine pharmacokinetics.", "content": "Pharmacokinetic research has shown that clear differences exist among benzodiazepines in rate and route of elimination and in the presence or absence of pharmacologically active metabolites. These findings and other results of pharmacokinetic research have clinical implications in terms of dosage schedules, drug accumulation during long-term therapy, antianxiety therapy in the elderly, drug interactions, pharmacotherapy in specific disease states, and the influence of route of administration on drug action.", "contents": "Clinical implications of benzodiazepine pharmacokinetics. Pharmacokinetic research has shown that clear differences exist among benzodiazepines in rate and route of elimination and in the presence or absence of pharmacologically active metabolites. These findings and other results of pharmacokinetic research have clinical implications in terms of dosage schedules, drug accumulation during long-term therapy, antianxiety therapy in the elderly, drug interactions, pharmacotherapy in specific disease states, and the influence of route of administration on drug action."}
{"id": "PMID:17303", "title": "The role of benzodiazepines in nonpsychiatric medical practice.", "content": "The benzodiazepines are widely prescribed by many physicians for patients with depression, anxiety reaction, circulatory disorders, digestive disorders, tension headache, and pain in chest and back. According to various studies there is reason to believe that benzodiazepines not only possess the anxiolytic effects universally attributed to them but may also ameliorate somatic complaints affecting such systems as the cardiovascular and the gastrointestinal. twhether the bensodiazepines affect organ systems known to be linked in important pathophysiological ways to the nervous system deserves further study.", "contents": "The role of benzodiazepines in nonpsychiatric medical practice. The benzodiazepines are widely prescribed by many physicians for patients with depression, anxiety reaction, circulatory disorders, digestive disorders, tension headache, and pain in chest and back. According to various studies there is reason to believe that benzodiazepines not only possess the anxiolytic effects universally attributed to them but may also ameliorate somatic complaints affecting such systems as the cardiovascular and the gastrointestinal. twhether the bensodiazepines affect organ systems known to be linked in important pathophysiological ways to the nervous system deserves further study."}
{"id": "PMID:17304", "title": "Brain mechanisms associated with therapeutic actions of benzodiazepines: focus on neurotransmitters.", "content": "The sedative, muscle relaxant, antianxiety, and anticonvulsant effects of benzodiazepines may involve several distinct mechanisms because dissociation among these actions can be demonstrated with various drugs. Neurotransmitters displaying prominent interactions with benzodiazepines include gamma-aminobutyric acid (GABA), glycine, norepinephrine, and serotonin.", "contents": "Brain mechanisms associated with therapeutic actions of benzodiazepines: focus on neurotransmitters. The sedative, muscle relaxant, antianxiety, and anticonvulsant effects of benzodiazepines may involve several distinct mechanisms because dissociation among these actions can be demonstrated with various drugs. Neurotransmitters displaying prominent interactions with benzodiazepines include gamma-aminobutyric acid (GABA), glycine, norepinephrine, and serotonin."}
{"id": "PMID:17305", "title": "Benzodiazepines: behavioral and neurochemical mechanisms.", "content": "The therapeutic effects of benzodiazepines in psychoneurosis may depend in part on their ability to release or disinhibit a patient's anxiety-suppressed gratification-seeking behavior. Benzodiazepines may disinhibit behavior by reducing the activity of serotonin (and possibly acetylcholine) neurons in the brain's \"punishment\" system. Reduction of serotonin transmission may be due to a facilitation of gamma-aminobutyric acid (GABA)-mediated presynaptic inhibition at the serotonin nerve terminal.", "contents": "Benzodiazepines: behavioral and neurochemical mechanisms. The therapeutic effects of benzodiazepines in psychoneurosis may depend in part on their ability to release or disinhibit a patient's anxiety-suppressed gratification-seeking behavior. Benzodiazepines may disinhibit behavior by reducing the activity of serotonin (and possibly acetylcholine) neurons in the brain's \"punishment\" system. Reduction of serotonin transmission may be due to a facilitation of gamma-aminobutyric acid (GABA)-mediated presynaptic inhibition at the serotonin nerve terminal."}
{"id": "PMID:17306", "title": "Neural mechanisms of benzodiazepine actions.", "content": "Current experimental paradigms emphasize neurotransmitter-specific interactions to explain the behavioral effects of benzodiazepines. According to this approach the broad range of effects observed suggests the involvement of several transmitter systems without rigorously establishing that any single transmitter system or physiological synaptic function is either necessary or sufficient to express all benzodiazepine actions. Among the effects that occur, potentiation of amino acid-mediated presynaptic inhibition in the spinal cord and postsynaptic inhibitions elsewhere in the brain are attractive testable hypotheses. However, direct physiological evidence that benzodiazepines stimulate gamma-aminobutyric acid (GABA) or other amino acids specifically and exclusively is needed to corroborate this view.", "contents": "Neural mechanisms of benzodiazepine actions. Current experimental paradigms emphasize neurotransmitter-specific interactions to explain the behavioral effects of benzodiazepines. According to this approach the broad range of effects observed suggests the involvement of several transmitter systems without rigorously establishing that any single transmitter system or physiological synaptic function is either necessary or sufficient to express all benzodiazepine actions. Among the effects that occur, potentiation of amino acid-mediated presynaptic inhibition in the spinal cord and postsynaptic inhibitions elsewhere in the brain are attractive testable hypotheses. However, direct physiological evidence that benzodiazepines stimulate gamma-aminobutyric acid (GABA) or other amino acids specifically and exclusively is needed to corroborate this view."}
{"id": "PMID:17308", "title": "Paradoxical response to dopamine agonists in tardive dyskinesia.", "content": "The authors conducted an extensive pharmacological analysis of a patient severely affected by tardive dyskinesia. No drug treatment gave lasting clinical improvement. Several agents recently recommended for this condition, dimethyl aminoethanol, clozapine, and thioridazine, failed to modify the dyskinesia. Reserpine caused a worsening of the symptoms. A paradoxical and unexpected improvement was observed with apomorphine injections and with low-dosage oral L-dopa. These two drugs may have acted by stimulating presynaptic inhibitory dopamine receptors.", "contents": "Paradoxical response to dopamine agonists in tardive dyskinesia. The authors conducted an extensive pharmacological analysis of a patient severely affected by tardive dyskinesia. No drug treatment gave lasting clinical improvement. Several agents recently recommended for this condition, dimethyl aminoethanol, clozapine, and thioridazine, failed to modify the dyskinesia. Reserpine caused a worsening of the symptoms. A paradoxical and unexpected improvement was observed with apomorphine injections and with low-dosage oral L-dopa. These two drugs may have acted by stimulating presynaptic inhibitory dopamine receptors."}
{"id": "PMID:17310", "title": "Host feeding patterns of Connecticut mosquitoes (Diptera: Culicidae).", "content": "Blood-engorged Coquillettidia perturbans, Psorophora ferox, Culex, Culiseta, and Aedes mosquitoes were collected principally by sweep net from salt marsh and woodland habitats in Connecticut. Of the 570 mosquitoes tested, precipitin tests identified the origins of 517 blood meals and revealed distinct host feeding patterns. Aedes mosquitoes fed chiefly on mammals; A. abserratus, A. cantator, and A. vexans showed selectivity for cattle and (or) horses. A. cantator also obtained blood from avian hosts and, in some instances, showed mixed passerine-mammal blood meals. These findings increase the vector potential of this salt marsh mosquito for eastern equine encephalomyelitis virus. Feedings on deer by A. abserratus suggest potential involvement of this mosquito in the transmission of certain subtypes of California encephalitis. Culex-pipiens, C. restuans, Culiseta melanura, and Cs. morsitans dyari acquired blood almost exclusively from passeriform birds.", "contents": "Host feeding patterns of Connecticut mosquitoes (Diptera: Culicidae). Blood-engorged Coquillettidia perturbans, Psorophora ferox, Culex, Culiseta, and Aedes mosquitoes were collected principally by sweep net from salt marsh and woodland habitats in Connecticut. Of the 570 mosquitoes tested, precipitin tests identified the origins of 517 blood meals and revealed distinct host feeding patterns. Aedes mosquitoes fed chiefly on mammals; A. abserratus, A. cantator, and A. vexans showed selectivity for cattle and (or) horses. A. cantator also obtained blood from avian hosts and, in some instances, showed mixed passerine-mammal blood meals. These findings increase the vector potential of this salt marsh mosquito for eastern equine encephalomyelitis virus. Feedings on deer by A. abserratus suggest potential involvement of this mosquito in the transmission of certain subtypes of California encephalitis. Culex-pipiens, C. restuans, Culiseta melanura, and Cs. morsitans dyari acquired blood almost exclusively from passeriform birds."}
{"id": "PMID:17311", "title": "Malignant hypertension as a cause of massive intestinal bleeding.", "content": "A forty-one year old man with a three year history of malignant hypertension developed massive rectal bleeding. A mesenteric arteriogram showed vascular changes compatible with necrotizing angitis. Histologic examination of the resected right hemicolon confirmed malignant hypertension as the cause of angitis.", "contents": "Malignant hypertension as a cause of massive intestinal bleeding. A forty-one year old man with a three year history of malignant hypertension developed massive rectal bleeding. A mesenteric arteriogram showed vascular changes compatible with necrotizing angitis. Histologic examination of the resected right hemicolon confirmed malignant hypertension as the cause of angitis."}
{"id": "PMID:17312", "title": "[Gerontology in rural and mountains regions aged people in the country and in mountain regions (author's transl)].", "content": "The gerontologic problems of people living in the country and in mountain regions always were neglected in comparison to those of townsmen. In the last decade an important structural change has happened, caused on the one side by the fact that more and more people leave the country for the towns, and by the problem of overaged persons in the country; on the other side this change is a consequence of improvement by modern technical acquisitions (more agricultural machines, silos), living hygiene and the tourism. The living conditions in the past and today in Switzerland are shown, referring to various publications. The ecological change also hits the aged people, financially by revenues, completion of private help organizations, rebuilding of homes for the aged persons in every village and regional nursing home, as well as household helps for those elderly people who still live in the country in their own houses. The qualitative differences between living conditions in the country and in town will in the near future be equalized--which is especially mentionned.", "contents": "[Gerontology in rural and mountains regions aged people in the country and in mountain regions (author's transl)]. The gerontologic problems of people living in the country and in mountain regions always were neglected in comparison to those of townsmen. In the last decade an important structural change has happened, caused on the one side by the fact that more and more people leave the country for the towns, and by the problem of overaged persons in the country; on the other side this change is a consequence of improvement by modern technical acquisitions (more agricultural machines, silos), living hygiene and the tourism. The living conditions in the past and today in Switzerland are shown, referring to various publications. The ecological change also hits the aged people, financially by revenues, completion of private help organizations, rebuilding of homes for the aged persons in every village and regional nursing home, as well as household helps for those elderly people who still live in the country in their own houses. The qualitative differences between living conditions in the country and in town will in the near future be equalized--which is especially mentionned."}
{"id": "PMID:17313", "title": "[Problems of aged people in rural regions of the Swiss Canton St. Gall (author's transl)].", "content": "Based on the structure of the mountain population, the living conditions of the aged (in rural communities 11-17% are older than 65) are shown. By public planning and cooperation of private organizations a material security of the aged has been strived after and mostly reached in the last 15 years--with the tendency to leave the aged in his own house or at least in the environment of his native village. Homes for the aged were built--if possible in every community--on the basis of 50 beds in a home for the aged and 35 beds in a nursing home for 10.000 inhabitants (83% in nursing homes an 17% in acute hospitals with geriatric departments). The individual help for the aged: activation by offering common institutions, ingenious activity, non-public advice offices, household help is deduced and the planning for the coming decade mentionned.", "contents": "[Problems of aged people in rural regions of the Swiss Canton St. Gall (author's transl)]. Based on the structure of the mountain population, the living conditions of the aged (in rural communities 11-17% are older than 65) are shown. By public planning and cooperation of private organizations a material security of the aged has been strived after and mostly reached in the last 15 years--with the tendency to leave the aged in his own house or at least in the environment of his native village. Homes for the aged were built--if possible in every community--on the basis of 50 beds in a home for the aged and 35 beds in a nursing home for 10.000 inhabitants (83% in nursing homes an 17% in acute hospitals with geriatric departments). The individual help for the aged: activation by offering common institutions, ingenious activity, non-public advice offices, household help is deduced and the planning for the coming decade mentionned."}
{"id": "PMID:17314", "title": "[Living conditions of the rural population in France. Situation in 1974 and evolution from 1967 to 1974 (author's transl)].", "content": "A survey of the living conditions of aged people in rural regions of France in 1974 and a comparison with the previous surveys of 1967/68 in 302 rural vallages are analysed. Of the 4,800 persons in 1967/68, by 1974 1,609 were dead (35%). After questioning the 2,191 living persons (1,275 farmers and 916 non farmers) an increased number of widowed people appeared in those 7 years. For men in 1967/68: 20%, now 28%; for women in 1967/68: 61%, now 72%. In the age group 75-79 three times more women lost their husbands than men lost their wives. 2/3 of the households remained identical, 1/5 became smaller, 1/8 increased. The comparison (excluding the dead persons) showed no significant differences in the health conditions. Detailed questions were asked regarding social relationships but it is very difficult to analyse the date due to the great number of dead persons. The difference between farmers (whose number decreases) and non farmers (whose number increases) is especially mentioned and specific problems are treated separately. In France ageing in rural areas is increasing rapidly: in 1968, 393 rural counties contained 20% of people aged 65 or more.", "contents": "[Living conditions of the rural population in France. Situation in 1974 and evolution from 1967 to 1974 (author's transl)]. A survey of the living conditions of aged people in rural regions of France in 1974 and a comparison with the previous surveys of 1967/68 in 302 rural vallages are analysed. Of the 4,800 persons in 1967/68, by 1974 1,609 were dead (35%). After questioning the 2,191 living persons (1,275 farmers and 916 non farmers) an increased number of widowed people appeared in those 7 years. For men in 1967/68: 20%, now 28%; for women in 1967/68: 61%, now 72%. In the age group 75-79 three times more women lost their husbands than men lost their wives. 2/3 of the households remained identical, 1/5 became smaller, 1/8 increased. The comparison (excluding the dead persons) showed no significant differences in the health conditions. Detailed questions were asked regarding social relationships but it is very difficult to analyse the date due to the great number of dead persons. The difference between farmers (whose number decreases) and non farmers (whose number increases) is especially mentioned and specific problems are treated separately. In France ageing in rural areas is increasing rapidly: in 1968, 393 rural counties contained 20% of people aged 65 or more."}
{"id": "PMID:17315", "title": "[Aging in cities and in the country (author's transl)].", "content": "A growing concern with ecological issues has led gerontologist to analyze the life-situation of aged people in cities and in the country more precisely. While it is generally assumed that aging in the country has advantages to aging in the city, statistical figures (e.g. income, living conditions, health status, educational opportunities, institutions for the aged) show that country dweller's \"cumulative disadvantages\" have to be taken into consideration, disadvantages caused by interacting societal and individual factors in rural life. Psychological investigations--as e.g. the Bonn Longitudinal Study of Aging (BLSA)--show positive correlations between a central location of the home and increased general activity, broader scope of interests, more frequent use of communication media (newspapers, newscasts), better mood, greater readiness for involvement. While city-dwellers are more frequently engaged in social contacts outside of the family, country dwellers are more involved in interactions with the immediate family. The following practical considerations for the improvement of the situation of the aged in the country are presented: beginning in childhood and youth, conditions should be granted which allow the individual to live in ways which prevent too early aging; this ought to be supplemented by providing activating and stimulating environments for aging people and help for the aged, be it in special institutions or through activities in their familiar environment. It is shown that a differential ecogerontology is required, since (1) a simple distinction between city and country is by far too global, (2) similar ecological conditions are known to have different effects, depending on inter-individual differences, and (3) intraindividual patterns, and (4) it becomes evident that objective ecological conditions do not as clearly determine behavior in age as do cognitive representations of these ecological variables. This last statement is in accordance with the cognitive theory of aging. There can be no doubt that ecological variables influence the process of aging, but there is nothing like the aging in the country.", "contents": "[Aging in cities and in the country (author's transl)]. A growing concern with ecological issues has led gerontologist to analyze the life-situation of aged people in cities and in the country more precisely. While it is generally assumed that aging in the country has advantages to aging in the city, statistical figures (e.g. income, living conditions, health status, educational opportunities, institutions for the aged) show that country dweller's \"cumulative disadvantages\" have to be taken into consideration, disadvantages caused by interacting societal and individual factors in rural life. Psychological investigations--as e.g. the Bonn Longitudinal Study of Aging (BLSA)--show positive correlations between a central location of the home and increased general activity, broader scope of interests, more frequent use of communication media (newspapers, newscasts), better mood, greater readiness for involvement. While city-dwellers are more frequently engaged in social contacts outside of the family, country dwellers are more involved in interactions with the immediate family. The following practical considerations for the improvement of the situation of the aged in the country are presented: beginning in childhood and youth, conditions should be granted which allow the individual to live in ways which prevent too early aging; this ought to be supplemented by providing activating and stimulating environments for aging people and help for the aged, be it in special institutions or through activities in their familiar environment. It is shown that a differential ecogerontology is required, since (1) a simple distinction between city and country is by far too global, (2) similar ecological conditions are known to have different effects, depending on inter-individual differences, and (3) intraindividual patterns, and (4) it becomes evident that objective ecological conditions do not as clearly determine behavior in age as do cognitive representations of these ecological variables. This last statement is in accordance with the cognitive theory of aging. There can be no doubt that ecological variables influence the process of aging, but there is nothing like the aging in the country."}
{"id": "PMID:17316", "title": "[The old aged in a mountain community (author's transl)].", "content": "In a mountain community of Eastern Switzerland at 1000 m with about 1000 people more than 17% are older than 65. 2/3 of the aged live in their own household, 1/4 lives together with the young generation. Only 8% spend their late years in a home for the aged, which lodges also easy nursing cases. Cheaper flats, cooperation in the farm (also in the home for the aged), economical style of living allow an adequate, satisfactory life in the well-known rural society.", "contents": "[The old aged in a mountain community (author's transl)]. In a mountain community of Eastern Switzerland at 1000 m with about 1000 people more than 17% are older than 65. 2/3 of the aged live in their own household, 1/4 lives together with the young generation. Only 8% spend their late years in a home for the aged, which lodges also easy nursing cases. Cheaper flats, cooperation in the farm (also in the home for the aged), economical style of living allow an adequate, satisfactory life in the well-known rural society."}
{"id": "PMID:17317", "title": "[Medical problems of the aged in a mountain community of the Swiss Canton Appenzell A.Rh. (author's transl)].", "content": "The report about a mountain community (Urn\u00e4sch) with 2400 inhabitants at 700-1100 m above sea level with 16-18% aged over 65 shows the help for the aged by several groups: women's club, church, cultural institutions. The community doctor looks after 4 homes for the aged. He also treats those patients living in their own houses. The aged usually prefere being nursed and dying at home in the shelter of the native mountain area.", "contents": "[Medical problems of the aged in a mountain community of the Swiss Canton Appenzell A.Rh. (author's transl)]. The report about a mountain community (Urn\u00e4sch) with 2400 inhabitants at 700-1100 m above sea level with 16-18% aged over 65 shows the help for the aged by several groups: women's club, church, cultural institutions. The community doctor looks after 4 homes for the aged. He also treats those patients living in their own houses. The aged usually prefere being nursed and dying at home in the shelter of the native mountain area."}
{"id": "PMID:17318", "title": "[The aged in a mountain region of the swiss grisons and their problems (author's transl)].", "content": "The way of life of the elderly people in a Swiss mountain valley (Schanfigg, Grisons) is statistically examined and illustrated by detailed descriptions. The author as general practitioner for the region (9 villages with a total of 1.500 persons, 20% over 65 years old) knows everybody personally. The majority of old people (75%) do no longer live together with the younger generation but are living in their own houses, either single or in \"symbiotic\" couples (married, relatives, other combinations). There is no shortage of living-quarters, partly due to the trend of depopulation. Besides the official national pension (AHV) there is no need for further financial administrative support; the everyday-supply is organizied by extensive house-delivery-services; practical assistance comes from the side of the neighbours or is realized within the symbiotic household. Medical services are available in any place and at any time; social activities could still be improved. According to their tradition and mentality the elderly people are living socially integrated in the community of the valley.", "contents": "[The aged in a mountain region of the swiss grisons and their problems (author's transl)]. The way of life of the elderly people in a Swiss mountain valley (Schanfigg, Grisons) is statistically examined and illustrated by detailed descriptions. The author as general practitioner for the region (9 villages with a total of 1.500 persons, 20% over 65 years old) knows everybody personally. The majority of old people (75%) do no longer live together with the younger generation but are living in their own houses, either single or in \"symbiotic\" couples (married, relatives, other combinations). There is no shortage of living-quarters, partly due to the trend of depopulation. Besides the official national pension (AHV) there is no need for further financial administrative support; the everyday-supply is organizied by extensive house-delivery-services; practical assistance comes from the side of the neighbours or is realized within the symbiotic household. Medical services are available in any place and at any time; social activities could still be improved. According to their tradition and mentality the elderly people are living socially integrated in the community of the valley."}
{"id": "PMID:17321", "title": "Endogenous opiates-a progress report.", "content": "The \"opiate receptor\" has become a  well-accepted entity, stimulating the search for an endogenous agonist. This has successfully revealed several different endogenous peptide opiates whose physiological role is under intense investigation, contributing to our understanding of pain and of opiate tolerance and dependence. A review of the current literature is presented.", "contents": "Endogenous opiates-a progress report. The \"opiate receptor\" has become a  well-accepted entity, stimulating the search for an endogenous agonist. This has successfully revealed several different endogenous peptide opiates whose physiological role is under intense investigation, contributing to our understanding of pain and of opiate tolerance and dependence. A review of the current literature is presented."}
{"id": "PMID:17335", "title": "Effect of sodium bicarbonate on canine left ventricular function.", "content": "Left ventricular performance was evaluated in seven canine right heart bypass preparations during and after the intraauricular administration of sodium bicarbonate (100 ml, 1100 Osm, 60 mEq). Under conditions of constant cardiac input and left ventricular volume, sodium bicarbonate produced mild and brief left ventricular depression, as manifested by a decline of left ventricular dp/dt with simultaneous rise of left ventricular end-diastrolic and left atrial pressures. These findings occurred as aortic impedance fell. Identical results accrued in paced and unpaced preparations. The data lends credence to the proposition that a sudden rise in blood pCO2 produces increased transport of CO2 across the cardiac membranes with intracellular acidosis. However, the data is also compatible with hyperosmolality induced contractile depression. Possible clinical implications are discussed.", "contents": "Effect of sodium bicarbonate on canine left ventricular function. Left ventricular performance was evaluated in seven canine right heart bypass preparations during and after the intraauricular administration of sodium bicarbonate (100 ml, 1100 Osm, 60 mEq). Under conditions of constant cardiac input and left ventricular volume, sodium bicarbonate produced mild and brief left ventricular depression, as manifested by a decline of left ventricular dp/dt with simultaneous rise of left ventricular end-diastrolic and left atrial pressures. These findings occurred as aortic impedance fell. Identical results accrued in paced and unpaced preparations. The data lends credence to the proposition that a sudden rise in blood pCO2 produces increased transport of CO2 across the cardiac membranes with intracellular acidosis. However, the data is also compatible with hyperosmolality induced contractile depression. Possible clinical implications are discussed."}
{"id": "PMID:17340", "title": "Secretin-stimulated serum gastrin levels in hyperparathyroid patients from families with multiple endocrine adenomatosis type I.", "content": "Twenty-three patients with hyperparathyroidism from six families with the multiple endocrine adenomatosis (MEA) I-syndrome were tested by secretin provocation. In nine cases this led to increases in serum gastrin ranging from 298 to 13 300 pg/ml, whereas the maximum rise in gastrin in the other 14 patients was 32 pg/ml. In all nine patients with marked gastrin responses to secretin, the Zollinger-Ellison syndrome was diagnosed by gastric acid hypersecretion and large increases in gastrin after calcium administration. Six of these nine patients had, at most, minor postprandial rises in gastin and two had demonstrable tumors. In 34 normal subjects, 23 nonaffected members of families with MEA I-syndrome, and 42 patients with various diseases the maximum gastrin response to secretin was 21 pg/ml. We conclude that secretin provocation is helpful in the diagnosis of the Zollinger-Ellison syndrome, especially when basal serum gastrin levels are only slightly elevated.", "contents": "Secretin-stimulated serum gastrin levels in hyperparathyroid patients from families with multiple endocrine adenomatosis type I. Twenty-three patients with hyperparathyroidism from six families with the multiple endocrine adenomatosis (MEA) I-syndrome were tested by secretin provocation. In nine cases this led to increases in serum gastrin ranging from 298 to 13 300 pg/ml, whereas the maximum rise in gastrin in the other 14 patients was 32 pg/ml. In all nine patients with marked gastrin responses to secretin, the Zollinger-Ellison syndrome was diagnosed by gastric acid hypersecretion and large increases in gastrin after calcium administration. Six of these nine patients had, at most, minor postprandial rises in gastin and two had demonstrable tumors. In 34 normal subjects, 23 nonaffected members of families with MEA I-syndrome, and 42 patients with various diseases the maximum gastrin response to secretin was 21 pg/ml. We conclude that secretin provocation is helpful in the diagnosis of the Zollinger-Ellison syndrome, especially when basal serum gastrin levels are only slightly elevated."}
{"id": "PMID:17344", "title": "[Cecal motility in the rabbit. III. Duality of fecal excretion].", "content": "The production of soft pellets (caecotrophs) was studied in conjunction with feeding behaviour, biochemical changes in caecal contents, motility of the caeco-colic region and transit of digesta in the colon in rabbits fed ad lib. or receiving one or two daily meals. Studies were carried out on animals either collared or free in their cages. Ingestion of soft pellets was recorded from electrodes fixed in the esophageal wall. Similar electrodes positioned on the caecum, proximal and distal colon and the fusus coli monitored regional electrical activity. Transit time for the colon was determined using a marker substance PSP. In animals fed ad lib. soft pellets were usually produced in the morning and this occurred 5 to 6 hours after the daily meal in the same animals. In subjects fasted for 15 hours, a daily meal was followed by increase in the volatile fatty acid concentration and decrease in the pH of caecal contents. Irrespective of the regimen the production of soft pellets coincided with a decrease in motility of both caecum and proximal colon and an increase in that of the distal colon. The transit time for the colon was 1.5 to 2.5 times faster for the production of soft than for the production of hard pellets.", "contents": "[Cecal motility in the rabbit. III. Duality of fecal excretion]. The production of soft pellets (caecotrophs) was studied in conjunction with feeding behaviour, biochemical changes in caecal contents, motility of the caeco-colic region and transit of digesta in the colon in rabbits fed ad lib. or receiving one or two daily meals. Studies were carried out on animals either collared or free in their cages. Ingestion of soft pellets was recorded from electrodes fixed in the esophageal wall. Similar electrodes positioned on the caecum, proximal and distal colon and the fusus coli monitored regional electrical activity. Transit time for the colon was determined using a marker substance PSP. In animals fed ad lib. soft pellets were usually produced in the morning and this occurred 5 to 6 hours after the daily meal in the same animals. In subjects fasted for 15 hours, a daily meal was followed by increase in the volatile fatty acid concentration and decrease in the pH of caecal contents. Irrespective of the regimen the production of soft pellets coincided with a decrease in motility of both caecum and proximal colon and an increase in that of the distal colon. The transit time for the colon was 1.5 to 2.5 times faster for the production of soft than for the production of hard pellets."}
{"id": "PMID:17347", "title": "Experiments for the production of graft-versus-host reaction in adult and infantile mice by means of human immunocompetent cells.", "content": "By administering anti-mouse ATS five times to random-bred Swiss albino mice weighing 16-18 and 10-11 g respectively, the authors have tried to produce immunological depression of such a degree which would allow living human leukocytes to cause GVH reaction. On the basis of the results it may be stated that with the serum dosage and manner of treatment applied, the human graft was not able to act against the recipient organism and to produce differences in body weight.", "contents": "Experiments for the production of graft-versus-host reaction in adult and infantile mice by means of human immunocompetent cells. By administering anti-mouse ATS five times to random-bred Swiss albino mice weighing 16-18 and 10-11 g respectively, the authors have tried to produce immunological depression of such a degree which would allow living human leukocytes to cause GVH reaction. On the basis of the results it may be stated that with the serum dosage and manner of treatment applied, the human graft was not able to act against the recipient organism and to produce differences in body weight."}
{"id": "PMID:17348", "title": "Exeriments for the production of graft-versus-host reaction in newborn mice by means of human immunocompetent cells.", "content": "It was not possible to produce the wasting disease in newborn mice by administering human leukocytes in Hanks' solution, or suspended in m-ATS or h-ATS. The attempt of the authors to produce immunosuppression by the administration of m-ATS started at newborn age-as a result of which the human immunocompetent cells would have produced serious GVH reaction-resulted only in a trend of GVH. The authors used only body weight measuring for detecting the GVH reaction. More sensitive parameters will be employed in their experiments in progress.", "contents": "Exeriments for the production of graft-versus-host reaction in newborn mice by means of human immunocompetent cells. It was not possible to produce the wasting disease in newborn mice by administering human leukocytes in Hanks' solution, or suspended in m-ATS or h-ATS. The attempt of the authors to produce immunosuppression by the administration of m-ATS started at newborn age-as a result of which the human immunocompetent cells would have produced serious GVH reaction-resulted only in a trend of GVH. The authors used only body weight measuring for detecting the GVH reaction. More sensitive parameters will be employed in their experiments in progress."}
{"id": "PMID:17349", "title": "Study on the interaction of lymphotropic cytostatic agent treatment and graft-versus-host (GVH) reaction in mice.", "content": "F1 hybrid mice (C57BL X C3H) suffering from graft-versus-host disease, were treated with dianhydrodulcit (DAD) a lymphotrop cytostatic agent. 15 mg/kg of the compound was injected intraperitoneally, 8 days following the administration of the parental spleen cell suspension. The interaction between the two interventions is discussed on the basis of the rate and time course of deaths observed is the individual groups, as well as on the state of the lymphoid organs of the succumbed and sacrificed animals.", "contents": "Study on the interaction of lymphotropic cytostatic agent treatment and graft-versus-host (GVH) reaction in mice. F1 hybrid mice (C57BL X C3H) suffering from graft-versus-host disease, were treated with dianhydrodulcit (DAD) a lymphotrop cytostatic agent. 15 mg/kg of the compound was injected intraperitoneally, 8 days following the administration of the parental spleen cell suspension. The interaction between the two interventions is discussed on the basis of the rate and time course of deaths observed is the individual groups, as well as on the state of the lymphoid organs of the succumbed and sacrificed animals."}
{"id": "PMID:17364", "title": "Oxidation of stibnite by Thiobacillus ferrooxidans.", "content": "Optimum pH, temperature and pulp density for microbiological leaching of museum-grade stibnite mineral has been investigated using a stibnite-adapted strain of Thiobacillus ferrooxidans. Optimum conditions were found to be pH  1.75, 35 C and 12g solid substrate per 100 ml of basal salts medium as the initial dose. The energy of activation was determined to be 16.8 kcal per mole, and the temperature coefficient 2.2. The highest total dissolved antimony concentration, [Sbt] = [Sb+3] + [sb+5] + I1SbO2+], was about 1400 mg/litre, due to relatively low solubility of (SbO)2SO4 and (SbO2)2SO4.", "contents": "Oxidation of stibnite by Thiobacillus ferrooxidans. Optimum pH, temperature and pulp density for microbiological leaching of museum-grade stibnite mineral has been investigated using a stibnite-adapted strain of Thiobacillus ferrooxidans. Optimum conditions were found to be pH  1.75, 35 C and 12g solid substrate per 100 ml of basal salts medium as the initial dose. The energy of activation was determined to be 16.8 kcal per mole, and the temperature coefficient 2.2. The highest total dissolved antimony concentration, [Sbt] = [Sb+3] + [sb+5] + I1SbO2+], was about 1400 mg/litre, due to relatively low solubility of (SbO)2SO4 and (SbO2)2SO4."}
{"id": "PMID:17365", "title": "Fungal growth on C1 compounds: quantitative aspects of growth of a methanol-utilizing strain of Trichoderma lignorum in batch culture.", "content": "A study was made of some salient parameters that influence growth of the methanol-utilizing fungus Trichoderma lignorum growing in batch culture on a minimal medium containing methanol as the sole source of carbon. Maximum cell yield was recorded at the expense of 1.58 g of methanol per liter. Inhibition was observed with methanol concentrations in excess of 4.7 g/liter. The optimum temperature for fungal growth was 23 degrees C. Growth of the fungus was directly proportional to an inorganic nitrogen concentration up to 0.2 g of NH4NO3 per liter. No inhibition of growth occurred at any concentration of NH4NO3 up to 11 g/liter. The pH of the growth medium decreased from 7.0 to 3.5 during growth of the fungus on methanol, which may have been due, in part, to the accumulation of trace amounts of organic acids in the growth medium. An analysis of the commercial potential of the fungus, as a source of edible protein, indicated that the strain of methanol-utilizing T. lignorum used was uneconomical in terms of the yield and the specific growth rate.", "contents": "Fungal growth on C1 compounds: quantitative aspects of growth of a methanol-utilizing strain of Trichoderma lignorum in batch culture. A study was made of some salient parameters that influence growth of the methanol-utilizing fungus Trichoderma lignorum growing in batch culture on a minimal medium containing methanol as the sole source of carbon. Maximum cell yield was recorded at the expense of 1.58 g of methanol per liter. Inhibition was observed with methanol concentrations in excess of 4.7 g/liter. The optimum temperature for fungal growth was 23 degrees C. Growth of the fungus was directly proportional to an inorganic nitrogen concentration up to 0.2 g of NH4NO3 per liter. No inhibition of growth occurred at any concentration of NH4NO3 up to 11 g/liter. The pH of the growth medium decreased from 7.0 to 3.5 during growth of the fungus on methanol, which may have been due, in part, to the accumulation of trace amounts of organic acids in the growth medium. An analysis of the commercial potential of the fungus, as a source of edible protein, indicated that the strain of methanol-utilizing T. lignorum used was uneconomical in terms of the yield and the specific growth rate."}
{"id": "PMID:17366", "title": "Iodination of staphylococcal enterotoxin B by use of chloramine-T.", "content": "This report describes the conditions that are necessary for iodination of staphylococcal enterotoxin B (SEB) by use of chloramine-T. Makor Chemical Co. SEB and the two major SEB components, which were prepared by isoelectric focusing of partially purified SEB, were used in these studies. The antigenic activity of the SEB preparations was monitored by radioimmunoassay as the oxidation/reduction (O/R) potential was increased by addition of chloramine-T. The SEB preparations lost antigenic activity rapidly at pH 7.5 and room temperature when sufficient chloramine-T was added to raise the O/R potential above 250 mV. Iodinated SEB with satisfactory immunoreactivity was prepared by omitting carrier iodide from the iodination reaction mixture and by using at least 1 mg of SEB/ml, steps which made the O/R potential more stable, and by stopping the reaction before the O/R potential exceeded 250 mV. Comparison of the chloramine-T method with a lactoperoxidase/H2O2 method of iodinating SEB showed the latter to cause a greater loss of immunoreactivity.", "contents": "Iodination of staphylococcal enterotoxin B by use of chloramine-T. This report describes the conditions that are necessary for iodination of staphylococcal enterotoxin B (SEB) by use of chloramine-T. Makor Chemical Co. SEB and the two major SEB components, which were prepared by isoelectric focusing of partially purified SEB, were used in these studies. The antigenic activity of the SEB preparations was monitored by radioimmunoassay as the oxidation/reduction (O/R) potential was increased by addition of chloramine-T. The SEB preparations lost antigenic activity rapidly at pH 7.5 and room temperature when sufficient chloramine-T was added to raise the O/R potential above 250 mV. Iodinated SEB with satisfactory immunoreactivity was prepared by omitting carrier iodide from the iodination reaction mixture and by using at least 1 mg of SEB/ml, steps which made the O/R potential more stable, and by stopping the reaction before the O/R potential exceeded 250 mV. Comparison of the chloramine-T method with a lactoperoxidase/H2O2 method of iodinating SEB showed the latter to cause a greater loss of immunoreactivity."}
{"id": "PMID:17367", "title": "Identification of the virucidal agent in wastewater sludge.", "content": "Anaerobically digested sludge contains an agent that causes irreversible inactivation of poliovirus. It has now been shown that the agent responsible for this activity is ammonia. The effect of ammonia on poliovirus appears to be typical for picornaviruses, but reovirus, an enteric virus of another group, is quite resistant to this compound. Because ammonia is not virucidal in its charged state, it expresses significant activity only at pH values greater than 8. Therefore, increasing the pH of sludge should cause rapid inactivation of indigenous picornaviruses.", "contents": "Identification of the virucidal agent in wastewater sludge. Anaerobically digested sludge contains an agent that causes irreversible inactivation of poliovirus. It has now been shown that the agent responsible for this activity is ammonia. The effect of ammonia on poliovirus appears to be typical for picornaviruses, but reovirus, an enteric virus of another group, is quite resistant to this compound. Because ammonia is not virucidal in its charged state, it expresses significant activity only at pH values greater than 8. Therefore, increasing the pH of sludge should cause rapid inactivation of indigenous picornaviruses."}
{"id": "PMID:17368", "title": "Graft-vs-host reaction.", "content": "Observations surrounding the clinical manifestations and pathological studies of a neonate who died at 9 weeks of age, indicate that distinctive cutaneous, histopathologic, and ultrastructural findings occur when graft-vs-host reaction (GVHR) complicates combined immune deficiency syndrome (CIDS). The prominence and specificity of the epidermal lesions, particularly a necrotic cell that occurs in association with satellite lymphocytes (\"satellite cell necrosis\" (SCN)), lead us to recommend that a cutaneous biopsy be performed to facilitate an early definitive diagnosis. Dermatologists can recognize GVHR at the bedside and establish the diagnosis with the pathological findings obtained from the skin biopsy.", "contents": "Graft-vs-host reaction. Observations surrounding the clinical manifestations and pathological studies of a neonate who died at 9 weeks of age, indicate that distinctive cutaneous, histopathologic, and ultrastructural findings occur when graft-vs-host reaction (GVHR) complicates combined immune deficiency syndrome (CIDS). The prominence and specificity of the epidermal lesions, particularly a necrotic cell that occurs in association with satellite lymphocytes (\"satellite cell necrosis\" (SCN)), lead us to recommend that a cutaneous biopsy be performed to facilitate an early definitive diagnosis. Dermatologists can recognize GVHR at the bedside and establish the diagnosis with the pathological findings obtained from the skin biopsy."}
{"id": "PMID:17370", "title": "Haemagglutination tests in the study of Ascaris epidemiology.", "content": "Haemagglutination tests using adult Ascaris suum antigen were performed on sera from 810 people from three areas in Papua New Guinea and East Timor. In the area with the highest childhood Ascaris infection rates and egg-counts (Kaul), titres were highest and remained high throughout life. There was a significant negative correlation between titre and eosinophil count, and it is suggested that high titres in adult life result from continuous usually unsuccessful reinfection, and that the declining egg-counts and infection rates with increasing age may be the result of an immune mechanism, and not decreased exposure. In the two other populations the less intense Ascaris infection was reflected in the lower titres, with no correlation between titres, infection or eosinophilia. Although the haemagglutination test as used here is unsuitable as a diagnostic aid, it is valuable in studying the epidemiology of Ascaris infections.", "contents": "Haemagglutination tests in the study of Ascaris epidemiology. Haemagglutination tests using adult Ascaris suum antigen were performed on sera from 810 people from three areas in Papua New Guinea and East Timor. In the area with the highest childhood Ascaris infection rates and egg-counts (Kaul), titres were highest and remained high throughout life. There was a significant negative correlation between titre and eosinophil count, and it is suggested that high titres in adult life result from continuous usually unsuccessful reinfection, and that the declining egg-counts and infection rates with increasing age may be the result of an immune mechanism, and not decreased exposure. In the two other populations the less intense Ascaris infection was reflected in the lower titres, with no correlation between titres, infection or eosinophilia. Although the haemagglutination test as used here is unsuitable as a diagnostic aid, it is valuable in studying the epidemiology of Ascaris infections."}
{"id": "PMID:17371", "title": "Effects of various neuroleptics on rabbit hyperthermia induced by N, N-Dimethyltryptamine (DMT) and d-amphetamine.", "content": "The effects of various neuroleptics were studied on N, N-dimethyltryptamine (DMT, 3.2 mg/kg) and d-amphetamine (3.2 mg/kg) induced hyperthermia in the rabbit. Complete dose-effect curves were obtained. The order of potency for antagonism of DMT-induced hyperthermia was: methiothepin greater than octoclothepin greater than or equal to oxyprothepin greater than perathiepin greater than dokloxythepin greater than mianserine greater than loxapine greater than oxypertine greater than chlorpromazine greater than pipamperone greater than fluphenazine greater than thiothixene greater than haloperidol greater than molindone. The order of potency for antagonism of d-amphetamine hyperthermia was: haloperidol greater than chlorpromazine greater than oxypertine greater than octoclothepin and methiothepin. For these five drugs, the order of potency for antagonism of amphetamine hyperthermia was the reverse of the order for antagonism of DMT hyperthermia. Methiothepin reduced d-amphetamine-induced hyperthermia effectively at a very high dose (0.32 mg/kg) and variably at lower doses. The results indicate that neuroleptics differ markedly in their specificity of antagonism of DMT and d-amphetamine which may act through different neurotransmitter mechanisms (tryptaminergic vs. adrenergic).", "contents": "Effects of various neuroleptics on rabbit hyperthermia induced by N, N-Dimethyltryptamine (DMT) and d-amphetamine. The effects of various neuroleptics were studied on N, N-dimethyltryptamine (DMT, 3.2 mg/kg) and d-amphetamine (3.2 mg/kg) induced hyperthermia in the rabbit. Complete dose-effect curves were obtained. The order of potency for antagonism of DMT-induced hyperthermia was: methiothepin greater than octoclothepin greater than or equal to oxyprothepin greater than perathiepin greater than dokloxythepin greater than mianserine greater than loxapine greater than oxypertine greater than chlorpromazine greater than pipamperone greater than fluphenazine greater than thiothixene greater than haloperidol greater than molindone. The order of potency for antagonism of d-amphetamine hyperthermia was: haloperidol greater than chlorpromazine greater than oxypertine greater than octoclothepin and methiothepin. For these five drugs, the order of potency for antagonism of amphetamine hyperthermia was the reverse of the order for antagonism of DMT hyperthermia. Methiothepin reduced d-amphetamine-induced hyperthermia effectively at a very high dose (0.32 mg/kg) and variably at lower doses. The results indicate that neuroleptics differ markedly in their specificity of antagonism of DMT and d-amphetamine which may act through different neurotransmitter mechanisms (tryptaminergic vs. adrenergic)."}
{"id": "PMID:17374", "title": "Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine.", "content": "According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.", "contents": "Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine. According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia."}
{"id": "PMID:17375", "title": "Blood serum peptidases in patients with ovarian carcinoma treated with Ledakrin.", "content": "The authors observed changes in activity of leucine amino-peptidase (E.C. 3.4.1.1--LAP), gamma-glutamyl transpeptidase (F.C 2.3.2.2--GGTP) and Co++-activated acylase in blood serum of patients with ovarian carcinoma, with or without ascites, treated with Ledakrin (1-nitro-9-[3-dimethylaminopropylamino] acridine). It was stated that the activities of LAP and GGTP increased during the treatment and during tumor progression. The level of Co++-activated acylase increased only slightly during the treatment and therefore, the determination of this enzyme appeared to be of no use in monitoring the therapy of ovarian carcinoma.", "contents": "Blood serum peptidases in patients with ovarian carcinoma treated with Ledakrin. The authors observed changes in activity of leucine amino-peptidase (E.C. 3.4.1.1--LAP), gamma-glutamyl transpeptidase (F.C 2.3.2.2--GGTP) and Co++-activated acylase in blood serum of patients with ovarian carcinoma, with or without ascites, treated with Ledakrin (1-nitro-9-[3-dimethylaminopropylamino] acridine). It was stated that the activities of LAP and GGTP increased during the treatment and during tumor progression. The level of Co++-activated acylase increased only slightly during the treatment and therefore, the determination of this enzyme appeared to be of no use in monitoring the therapy of ovarian carcinoma."}
{"id": "PMID:17376", "title": "[Ways of correcting certain metabolic processes in the myocardium in myocardial insufficiency].", "content": "The article deals with the following trends along which according to the author, investigations aimed at search for ways of correcting disturbed metabolic processes in the cardiac muscle in its incompetence should develop: 1) restoration of properties of contractile proteins and creation of a basis for successful formation of the processes of compensatory hyperfunction and hypertrophy of the myocardium; 2) correction of the electrolytic balance with regulation of the skin mechanisms of the process of contraction of myofibrils; 3) restoration of the energy potential of cells; 4) withdrawal of the damaging effect upon the myocardium of some products of its disturbed metabolism.", "contents": "[Ways of correcting certain metabolic processes in the myocardium in myocardial insufficiency]. The article deals with the following trends along which according to the author, investigations aimed at search for ways of correcting disturbed metabolic processes in the cardiac muscle in its incompetence should develop: 1) restoration of properties of contractile proteins and creation of a basis for successful formation of the processes of compensatory hyperfunction and hypertrophy of the myocardium; 2) correction of the electrolytic balance with regulation of the skin mechanisms of the process of contraction of myofibrils; 3) restoration of the energy potential of cells; 4) withdrawal of the damaging effect upon the myocardium of some products of its disturbed metabolism."}
{"id": "PMID:17377", "title": "[Use of formaldehyde with pH 8 0 as a fixative for electron and fluorescence microscopy].", "content": "For fixation of the material to be investigated at the light and ultrastuctural level the author suggests to use 4% formaldehyde obtained by depolymerization of paraform on 0.1 M phosphate buffer with end pH 8.0 of the solution. This fixative stabilizes well glycogen and tissue structure. The ultrastructural characteristics of cells following continuous (up to 130 days) fixation are comparable with those obtained after fixation with aldehydes by conventional techniques. Results of histological PAS test, Feulgen's reactions and those to acid polycaccharides were identical to the results obtained in fixation with neutralized formalin. The possibility of prolonged storage of tissues makes it possible to perform delayed and repeated ultrastructural investigations of clinical and experimental material.", "contents": "[Use of formaldehyde with pH 8 0 as a fixative for electron and fluorescence microscopy]. For fixation of the material to be investigated at the light and ultrastuctural level the author suggests to use 4% formaldehyde obtained by depolymerization of paraform on 0.1 M phosphate buffer with end pH 8.0 of the solution. This fixative stabilizes well glycogen and tissue structure. The ultrastructural characteristics of cells following continuous (up to 130 days) fixation are comparable with those obtained after fixation with aldehydes by conventional techniques. Results of histological PAS test, Feulgen's reactions and those to acid polycaccharides were identical to the results obtained in fixation with neutralized formalin. The possibility of prolonged storage of tissues makes it possible to perform delayed and repeated ultrastructural investigations of clinical and experimental material."}
{"id": "PMID:17378", "title": "Hydrogen ion concentration of human tears: Effects of prolonged eye closure.", "content": "Using a closed chamber microelectrode technique, human tear hydrogen ion concentration was measured following periods of eye closure of 6 to 8 hours and then compared with normal open eye findings from the same patients. Closed eye tears were found to be significantly more acid (average age difference = 26 nM/1) and required some 3 to 4 hours to return to average open eye levels. The population rate for this return averaged 6.9 nM/1/hr. This degree of acid shift measured for prolonged eye closure, however, remained, for the average patient, well within comfort limits commonly cited, and appeared insufficient to distrub the water content or optical parameters of hydrophilic polymers in common use today for therapeutic or cosmetic purposes.", "contents": "Hydrogen ion concentration of human tears: Effects of prolonged eye closure. Using a closed chamber microelectrode technique, human tear hydrogen ion concentration was measured following periods of eye closure of 6 to 8 hours and then compared with normal open eye findings from the same patients. Closed eye tears were found to be significantly more acid (average age difference = 26 nM/1) and required some 3 to 4 hours to return to average open eye levels. The population rate for this return averaged 6.9 nM/1/hr. This degree of acid shift measured for prolonged eye closure, however, remained, for the average patient, well within comfort limits commonly cited, and appeared insufficient to distrub the water content or optical parameters of hydrophilic polymers in common use today for therapeutic or cosmetic purposes."}
{"id": "PMID:17380", "title": "Surgery for unstable angina.", "content": "A series of 84 patients with unstable angina, treated surgically by grafting procedures between October 1970 and September 1976, have been reviewed. The study indicates that extensive coronary artery disease is common in these patients, and suggests that operation may favourably influence mortality, both immediate and delayed, but does not reduce the risk of myocardial infarction. Eighty per cent of the patients were relieved of angina and able to lead a reasonably normal existence.", "contents": "Surgery for unstable angina. A series of 84 patients with unstable angina, treated surgically by grafting procedures between October 1970 and September 1976, have been reviewed. The study indicates that extensive coronary artery disease is common in these patients, and suggests that operation may favourably influence mortality, both immediate and delayed, but does not reduce the risk of myocardial infarction. Eighty per cent of the patients were relieved of angina and able to lead a reasonably normal existence."}
{"id": "PMID:17381", "title": "Rapid inpatient treatment of severe female sexual dysfunction.", "content": "A mult-faceted inpatient programme for overcoming severe female sexual of dysfunction using behavior modification techniques is described. The results obtained in a pilot study on 17 consecutive patients are presenre present.", "contents": "Rapid inpatient treatment of severe female sexual dysfunction. A mult-faceted inpatient programme for overcoming severe female sexual of dysfunction using behavior modification techniques is described. The results obtained in a pilot study on 17 consecutive patients are presenre present."}
{"id": "PMID:17386", "title": "Properties of glutathione release observed during reduction of organic hydroperoxide, demethylation of aminopyrine and oxidation of some substances in perfused rat liver, and their implications for the physiological function of catalase.", "content": "The enhanced reduction of t-butyl hydroperoxide by glutathione peroxidase is accompanied by a decrease in the cellular concentration of both glutathione and NADPH in isolated liver cells, resulting in the release of GSSG (oxidized glutathione) from the perfused rat liver. This phenomenon, first reported by H. Sies, C. Gerstenecker, H. Menzel & L. Floh\u00e9 (1972) (FEBS Lett. 27, 171-175), can be observed under a variety of conditions, not only with the acceleration of the glutathione peroxidase reaction by organic peroxides, but also during the oxidation of glycollate and benzylamine, during demethylation of aminopyrine in the liver of the phenobarbital-pretreated rat and during oxidation of uric acid in the liver of the starved rat pretreated with 3-amino-1,2,4-triazole. The rate of release of GSSG is altered markedly by changes in the metabolic conditions which affect the rate of hepatic NADPH generation. Thus, regardless of whether achieved by enhanced oxidation of glutathione by glutathione peroxidase or by oxidation of NADPH through other metabolic pathways, an increase in the cellular concentration of GSSG appears to facilitate its release. It has been found that, in addition to the hexose monophosphate shunt, the mitochondrial NADH-NADP+ transhydrogenase reaction plays an important role in supplying reducing equivalents to the glutathione peroxidase reaction and in maintaining the cellular oxidation-reduction state of the nicotinamide nucleotides. Spectrophotometric analysis of the steady-state concentration of the catalase-H2O2 intermediate with simultaneous measurement of the rate of release of GSSG leads to the conclusion that intracellular compartmentation of catalase in the peroxisomes and glutathione peroxidase in the cytosol and mitochondria distinguishes the reactivities of these enzymes one from the other, and facilitates their effective cooperation in hydroperoxide metabolism in the liver.", "contents": "Properties of glutathione release observed during reduction of organic hydroperoxide, demethylation of aminopyrine and oxidation of some substances in perfused rat liver, and their implications for the physiological function of catalase. The enhanced reduction of t-butyl hydroperoxide by glutathione peroxidase is accompanied by a decrease in the cellular concentration of both glutathione and NADPH in isolated liver cells, resulting in the release of GSSG (oxidized glutathione) from the perfused rat liver. This phenomenon, first reported by H. Sies, C. Gerstenecker, H. Menzel & L. Floh\u00e9 (1972) (FEBS Lett. 27, 171-175), can be observed under a variety of conditions, not only with the acceleration of the glutathione peroxidase reaction by organic peroxides, but also during the oxidation of glycollate and benzylamine, during demethylation of aminopyrine in the liver of the phenobarbital-pretreated rat and during oxidation of uric acid in the liver of the starved rat pretreated with 3-amino-1,2,4-triazole. The rate of release of GSSG is altered markedly by changes in the metabolic conditions which affect the rate of hepatic NADPH generation. Thus, regardless of whether achieved by enhanced oxidation of glutathione by glutathione peroxidase or by oxidation of NADPH through other metabolic pathways, an increase in the cellular concentration of GSSG appears to facilitate its release. It has been found that, in addition to the hexose monophosphate shunt, the mitochondrial NADH-NADP+ transhydrogenase reaction plays an important role in supplying reducing equivalents to the glutathione peroxidase reaction and in maintaining the cellular oxidation-reduction state of the nicotinamide nucleotides. Spectrophotometric analysis of the steady-state concentration of the catalase-H2O2 intermediate with simultaneous measurement of the rate of release of GSSG leads to the conclusion that intracellular compartmentation of catalase in the peroxisomes and glutathione peroxidase in the cytosol and mitochondria distinguishes the reactivities of these enzymes one from the other, and facilitates their effective cooperation in hydroperoxide metabolism in the liver."}
{"id": "PMID:17387", "title": "A kinetic study of the soluble 5'-nucleotidase of rat liver.", "content": "1. The kinetic properties of the 5'-nucleotidase (EC 3.1.3.5) present in the cytosol of rat liver were investigated in relation to the conversion of adenine nucleotides into uric acid, with particular reference to the stimulation of this process by fructose. The enzyme was assayed by the release of Pi and by a new and more sensitive radiochemical procedure. 2. When IMP was used as substrate, the partially purified enzyme displayed almost hyperbolic kinetics (h = 1.1) with S0.5 = 1.2 mM. Similar kinetics were observed with GMP and other nucleoside 5'-monophosphates, except AMP. 3. Vmax. of the enzyme for AMP was about the same as for IMP, but the kinetics were sigmoidal (h = 1.6) with S 0.5 = 10 mM. 4. The hydrolysis of IMP was inhibited competitively by GMP. IMP, at concentrations up to 0.5 mM, had a paradoxical stimulatory action on the hydrolysis of 2-5 mM-AMP and was inhibitory at higher concentrations. 5. The activity of the enzyme towards AMP and IMP was stimulated by ATP and GTP, and inhibited by Pi. Activators and inhibitor approximately cancelled each others' effects. At pH 7.4, the enzymic activity with 0.2 mM-AMP was undetectable under physiological conditions. 6. It is concluded that, in the liver cell, AMP is not hydrolysed by the soluble 5'-nucleotidase, but that its degradation requires prior deamination to IMP.", "contents": "A kinetic study of the soluble 5'-nucleotidase of rat liver. 1. The kinetic properties of the 5'-nucleotidase (EC 3.1.3.5) present in the cytosol of rat liver were investigated in relation to the conversion of adenine nucleotides into uric acid, with particular reference to the stimulation of this process by fructose. The enzyme was assayed by the release of Pi and by a new and more sensitive radiochemical procedure. 2. When IMP was used as substrate, the partially purified enzyme displayed almost hyperbolic kinetics (h = 1.1) with S0.5 = 1.2 mM. Similar kinetics were observed with GMP and other nucleoside 5'-monophosphates, except AMP. 3. Vmax. of the enzyme for AMP was about the same as for IMP, but the kinetics were sigmoidal (h = 1.6) with S 0.5 = 10 mM. 4. The hydrolysis of IMP was inhibited competitively by GMP. IMP, at concentrations up to 0.5 mM, had a paradoxical stimulatory action on the hydrolysis of 2-5 mM-AMP and was inhibitory at higher concentrations. 5. The activity of the enzyme towards AMP and IMP was stimulated by ATP and GTP, and inhibited by Pi. Activators and inhibitor approximately cancelled each others' effects. At pH 7.4, the enzymic activity with 0.2 mM-AMP was undetectable under physiological conditions. 6. It is concluded that, in the liver cell, AMP is not hydrolysed by the soluble 5'-nucleotidase, but that its degradation requires prior deamination to IMP."}
{"id": "PMID:17388", "title": "Changes in mammary-gland acetyl-coenzyme A carboxylase associated with lactogenic differentiation.", "content": "The process leading to the rise of acetyl-CoA carboxylase activity in rat mammary tissue after the onset of lactation was investigated. The kinetics of change in enzyme activity and enzyme immunotitratable with antibody against avian liver acetyl-CoA carboxylase were determined during the course of lactogenic differentiation. The antibody inactivates and specifically precipitates acetyl-CoA carboxylase from rat mammary tissue as well as that from chicken liver cytosol. Characterization of the immunoprecipitate of the mammary tissue carboxylase by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis reveals a single biotin-containing polypeptide of about 230000mol.wt. This molecular weight is approximately twice that reported for the avian liver enzyme. However, chicken liver cytosol prepared in the presence of trypsin inhibitor and subjected to immunoprecipitation gives rise to a biotin-containing subunit of 230000mol.wt. as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis; omission of proteinase inhibitor leads to a subunit(s) approximately one-half this size. Throughout gestation both carboxylase activity and amounts of immunotitratable enzyme remained low; however, after parturition both parameters rose concomitantly to values 30-40 times the initial values. Therefore the elevated concentration of acetyl-CoA carboxylase appears to result from an increased rate of synthesis of enzyme relative to degradation rather than to activation of a pre-existing form of the enzyme.", "contents": "Changes in mammary-gland acetyl-coenzyme A carboxylase associated with lactogenic differentiation. The process leading to the rise of acetyl-CoA carboxylase activity in rat mammary tissue after the onset of lactation was investigated. The kinetics of change in enzyme activity and enzyme immunotitratable with antibody against avian liver acetyl-CoA carboxylase were determined during the course of lactogenic differentiation. The antibody inactivates and specifically precipitates acetyl-CoA carboxylase from rat mammary tissue as well as that from chicken liver cytosol. Characterization of the immunoprecipitate of the mammary tissue carboxylase by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis reveals a single biotin-containing polypeptide of about 230000mol.wt. This molecular weight is approximately twice that reported for the avian liver enzyme. However, chicken liver cytosol prepared in the presence of trypsin inhibitor and subjected to immunoprecipitation gives rise to a biotin-containing subunit of 230000mol.wt. as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis; omission of proteinase inhibitor leads to a subunit(s) approximately one-half this size. Throughout gestation both carboxylase activity and amounts of immunotitratable enzyme remained low; however, after parturition both parameters rose concomitantly to values 30-40 times the initial values. Therefore the elevated concentration of acetyl-CoA carboxylase appears to result from an increased rate of synthesis of enzyme relative to degradation rather than to activation of a pre-existing form of the enzyme."}
{"id": "PMID:17389", "title": "Possible multiple binding sites for o-aminophenol on uridine diphosphate glucuronyltransferase.", "content": "1. Hepatic microsomal UDP-glucuronyltransferase (EC 2.4.1.17) derived from either weanling or adult rats exhibits three pH optima, at pH 5.4, 7.2 and 9.2, when o-aminophenol is the acceptor substrate, whereas p-nitrophenol is the acceptor substrate only on pH optimum is observed, at pH 5.4.2. Prior treatment of rats of either age with 3-methylcholanthrene results in a 2-3-fold increase in o-aminophenol conjugation at pH 5.4 and a 6-9-fold increase at pH 9.2. At pH 7.2, the induced enzyme is 2 to 3 times more active towards o-aminophenol than the control enzyme, but no pH optimum is demonstrable. 3. o-Aminophenol conjugation at pH 5.4 and 9.2 is inhibited competitively by both p-nitrophenol and p-nitrophenyl glucuronide, suggesting that the two phenolic aglycones share the same binding site. At pH 7.2, however, p-nitrophenyl glucuronide does not inhibit o-aminophenol conjugation, suggesting that the binding site at this pH is not shared by the two phenols. These data are consistent with the existence of more than one binding site for o-aminophenol on UDP-glucuronyltransferase.", "contents": "Possible multiple binding sites for o-aminophenol on uridine diphosphate glucuronyltransferase. 1. Hepatic microsomal UDP-glucuronyltransferase (EC 2.4.1.17) derived from either weanling or adult rats exhibits three pH optima, at pH 5.4, 7.2 and 9.2, when o-aminophenol is the acceptor substrate, whereas p-nitrophenol is the acceptor substrate only on pH optimum is observed, at pH 5.4.2. Prior treatment of rats of either age with 3-methylcholanthrene results in a 2-3-fold increase in o-aminophenol conjugation at pH 5.4 and a 6-9-fold increase at pH 9.2. At pH 7.2, the induced enzyme is 2 to 3 times more active towards o-aminophenol than the control enzyme, but no pH optimum is demonstrable. 3. o-Aminophenol conjugation at pH 5.4 and 9.2 is inhibited competitively by both p-nitrophenol and p-nitrophenyl glucuronide, suggesting that the two phenolic aglycones share the same binding site. At pH 7.2, however, p-nitrophenyl glucuronide does not inhibit o-aminophenol conjugation, suggesting that the binding site at this pH is not shared by the two phenols. These data are consistent with the existence of more than one binding site for o-aminophenol on UDP-glucuronyltransferase."}
{"id": "PMID:17390", "title": "Purification of two hexosaminidases from human kidney.", "content": "Hexosaminidase forms A and B were isolated from human kidney in a homogeneous state as demonstrated by electrophoretic and enzymic criteria. The enzymes were stable for at least 18 months when stored at -20 degrees C in 0.025 M-phosphate buffer, pH 6.5. The molecular weights of forms A and B were estimated by gel filtration to be 111 000 +/- 1500 and 114 000 +/- 1600 respectively. The molecular weights of hexosamidase A and B subunits were determined by using polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. Hexosaminidase A dissociated into one subunit with mol.wt. 68 000. Hexosaminidase B dissociated into three subunits with mol. wts. 100 000, 68 000 and 37000 respectively, and one protein band of mol.wt. 140 000. After treatment of hexosaminidases A and B with iodoacetic acid, the molecular weights of the carboxymethylated polypeptide subunits were also estimated. Carboxymethylated hexosaminidase A dissociated into one major subunit of mol.wt. 18 000 and two other protein bands of mol.wts. 65 000 and 100 000. Carboxymethylated hexosaminidase B dissociated into one major subunit for mol.wt. 19 000 and an additional band of mol.wt. 37 000. The Km of the enzymes for the synthetic substrate p-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside was 0.8 mM. Both enzymes were inhibited or activated by various metal ions. Double pH optima for the enzymes were found at pH 4.5 and 4.8.", "contents": "Purification of two hexosaminidases from human kidney. Hexosaminidase forms A and B were isolated from human kidney in a homogeneous state as demonstrated by electrophoretic and enzymic criteria. The enzymes were stable for at least 18 months when stored at -20 degrees C in 0.025 M-phosphate buffer, pH 6.5. The molecular weights of forms A and B were estimated by gel filtration to be 111 000 +/- 1500 and 114 000 +/- 1600 respectively. The molecular weights of hexosamidase A and B subunits were determined by using polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. Hexosaminidase A dissociated into one subunit with mol.wt. 68 000. Hexosaminidase B dissociated into three subunits with mol. wts. 100 000, 68 000 and 37000 respectively, and one protein band of mol.wt. 140 000. After treatment of hexosaminidases A and B with iodoacetic acid, the molecular weights of the carboxymethylated polypeptide subunits were also estimated. Carboxymethylated hexosaminidase A dissociated into one major subunit of mol.wt. 18 000 and two other protein bands of mol.wts. 65 000 and 100 000. Carboxymethylated hexosaminidase B dissociated into one major subunit for mol.wt. 19 000 and an additional band of mol.wt. 37 000. The Km of the enzymes for the synthetic substrate p-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside was 0.8 mM. Both enzymes were inhibited or activated by various metal ions. Double pH optima for the enzymes were found at pH 4.5 and 4.8."}
{"id": "PMID:17391", "title": "The kinetics of the recombination reaction between apomyoglobin and alkaline haematin.", "content": "Apomyoglobin was prepared by an extremely mild modification of the acid/butanone technique, and the kinetics of the recombination reaction between this preparation and alkaline haematin were studied. The recombination has been shown to be precisely second-order and mono-phasic. Rate constants obtained from the study are in good agreement with values obtained previously by an indirect technique not involving separation of haem and apoprotein.", "contents": "The kinetics of the recombination reaction between apomyoglobin and alkaline haematin. Apomyoglobin was prepared by an extremely mild modification of the acid/butanone technique, and the kinetics of the recombination reaction between this preparation and alkaline haematin were studied. The recombination has been shown to be precisely second-order and mono-phasic. Rate constants obtained from the study are in good agreement with values obtained previously by an indirect technique not involving separation of haem and apoprotein."}
{"id": "PMID:17392", "title": "Assay of flavin nucleotides in pancreatic islets by a differential fluorimetric technique.", "content": "Differences in fluorescence intensity between FMN and FAD at high and low pH values were utilized to determine the concentration of each nucleotide. Amounts down to 1 pmol were measurable. The FMN and FAD contents of pancreatic islets of obese-hyperglycaemic mice (gene symbol ob/ob) were compared with those of the exocrine pancreas, the liver and heart muscle. As expected, the FAD content of each tissue was greater than that of FMN. The contents of both nucleotides were significantly higher in the islets than in the exocrine part of the pancreas, but lower than in the heart muscle and liver. Possible relationships between the flavin content of the islets and their capacity for oxidative phosphorylation are briefly discussed.", "contents": "Assay of flavin nucleotides in pancreatic islets by a differential fluorimetric technique. Differences in fluorescence intensity between FMN and FAD at high and low pH values were utilized to determine the concentration of each nucleotide. Amounts down to 1 pmol were measurable. The FMN and FAD contents of pancreatic islets of obese-hyperglycaemic mice (gene symbol ob/ob) were compared with those of the exocrine pancreas, the liver and heart muscle. As expected, the FAD content of each tissue was greater than that of FMN. The contents of both nucleotides were significantly higher in the islets than in the exocrine part of the pancreas, but lower than in the heart muscle and liver. Possible relationships between the flavin content of the islets and their capacity for oxidative phosphorylation are briefly discussed."}
{"id": "PMID:17393", "title": "The highly electrophilic character of 4-chloro-7-nitrobenzofurazan and possible consequences for its application as a protein-labelling reagent.", "content": "4-Chloro-7-nitrobenzofurazan possesses at least one highly electrophilic centre (C-6) that is much more reactive towards nucleophiles than position C-4, the irreversible alkylating site of this reagent. Possible consequences of the electrophilic character of 4-chloro-7-nitrobenzofurazan for its application as a protein-labelling reagent are discussed.", "contents": "The highly electrophilic character of 4-chloro-7-nitrobenzofurazan and possible consequences for its application as a protein-labelling reagent. 4-Chloro-7-nitrobenzofurazan possesses at least one highly electrophilic centre (C-6) that is much more reactive towards nucleophiles than position C-4, the irreversible alkylating site of this reagent. Possible consequences of the electrophilic character of 4-chloro-7-nitrobenzofurazan for its application as a protein-labelling reagent are discussed."}
{"id": "PMID:17394", "title": "Acid dissociation constants of glycopeptides.", "content": "Glycopeptides containing mainly four amino acid residues in the sequence Asn-Leu-Thr-Ser, with small amounts of additional amino acid residues, were isolated from enzymic hydrolysates of hen's-egg albumin. Heterogeneity of the carbohydrate moiety was confirmed. Acid-base titrations showed that the alpha-amino group has a pKa value of 6.43 at 25 degrees C. The standard free engery and entropy changes associated with the ionization at 25 degrees C were 37.2kJ-mol-1 and -0.014kJ-mol-1- K-1 respectively. The complications arising in the interpretation of titration curves of the glycopeptides, which are heterogeneous with respect to the peptide chain, were considered and discussed in the light of the earlier suggestion that the titration curve of the glycopeptide might be interpreted as being due in part to a structure in which the hydroxyl group of the threonine residue is hydrogen-bonded to the beta-aspartamido oxygen atom [Neuberger & Marshall (1968) in Symposium on Foods - Carbohydrates and their Roles (Schultz, H.W., Cain, R.F. & Wrolstad, R.W., eds.), pp. 115-132, Avi Publishing Co., Westport, CT]. It is concluded that either the glycopeptides do not contain a hydrogen bond of that type, or, if they do, that it cannot be recognized by acid-base-titration studies.", "contents": "Acid dissociation constants of glycopeptides. Glycopeptides containing mainly four amino acid residues in the sequence Asn-Leu-Thr-Ser, with small amounts of additional amino acid residues, were isolated from enzymic hydrolysates of hen's-egg albumin. Heterogeneity of the carbohydrate moiety was confirmed. Acid-base titrations showed that the alpha-amino group has a pKa value of 6.43 at 25 degrees C. The standard free engery and entropy changes associated with the ionization at 25 degrees C were 37.2kJ-mol-1 and -0.014kJ-mol-1- K-1 respectively. The complications arising in the interpretation of titration curves of the glycopeptides, which are heterogeneous with respect to the peptide chain, were considered and discussed in the light of the earlier suggestion that the titration curve of the glycopeptide might be interpreted as being due in part to a structure in which the hydroxyl group of the threonine residue is hydrogen-bonded to the beta-aspartamido oxygen atom [Neuberger & Marshall (1968) in Symposium on Foods - Carbohydrates and their Roles (Schultz, H.W., Cain, R.F. & Wrolstad, R.W., eds.), pp. 115-132, Avi Publishing Co., Westport, CT]. It is concluded that either the glycopeptides do not contain a hydrogen bond of that type, or, if they do, that it cannot be recognized by acid-base-titration studies."}
{"id": "PMID:17395", "title": "The apparent absence of involvement of biotin in the vitamin K-dependent carboxylation of glutamic acid residues of proteins.", "content": "The mechanism of the vitamin K-dependent post-translational carboxylation of the gamma-carbon atom of glutamic acid residues in proteins remains obscure. Experiments were performed in vivo and in vitro in an attempt to establish a role for biotin in the transfer of the carboxyl group. Weanling male rats were fed on a biotin-deficient diet until severe biotin deficiency was induced. Their degree of biotin deficiency was documented by assaying for liver acetyl-CoA carboxylase activity, which was about 15% of normal. However, one-stage and two-stage prothrombin times measured on the plasmas were normal. In addition, the liver microsomal fraction did not contain any more prothrombin precursor than did that of normal rat liver. Experiments were done in vitro in which vitamin K-dependent fixing of 14CO2 was measured in the liver microsomal fraction from vitamin K-deficient male rats in the presence or absence of avidin. No evidence for an avidin-sensitive critical biotin-containing site was obtained. Thus neither series of experiments suggests a role for biotin; the data are compatible with carboxyl transfer occurring either through a carboxylated vitamin K intermediate; or via a yet to be identified intermediate, or perhaps via CO2 itself.", "contents": "The apparent absence of involvement of biotin in the vitamin K-dependent carboxylation of glutamic acid residues of proteins. The mechanism of the vitamin K-dependent post-translational carboxylation of the gamma-carbon atom of glutamic acid residues in proteins remains obscure. Experiments were performed in vivo and in vitro in an attempt to establish a role for biotin in the transfer of the carboxyl group. Weanling male rats were fed on a biotin-deficient diet until severe biotin deficiency was induced. Their degree of biotin deficiency was documented by assaying for liver acetyl-CoA carboxylase activity, which was about 15% of normal. However, one-stage and two-stage prothrombin times measured on the plasmas were normal. In addition, the liver microsomal fraction did not contain any more prothrombin precursor than did that of normal rat liver. Experiments were done in vitro in which vitamin K-dependent fixing of 14CO2 was measured in the liver microsomal fraction from vitamin K-deficient male rats in the presence or absence of avidin. No evidence for an avidin-sensitive critical biotin-containing site was obtained. Thus neither series of experiments suggests a role for biotin; the data are compatible with carboxyl transfer occurring either through a carboxylated vitamin K intermediate; or via a yet to be identified intermediate, or perhaps via CO2 itself."}
{"id": "PMID:17396", "title": "The binding of calcium to a salivary phosphoprotein, protein C, and comparison with calcium binding to protein A, a related salivary phosphoprotein.", "content": "The binding of Ca2+ to a salivary phosphoprotein, protein C, was studied by equilibrium dialysis. In 5mM-Tris/HCl buffer, pH 7.5, protein C bound 190 nmol of Ca2+/mg of protein. The apparent dissociation constant, K, was determined to be 1.9 x 10(-4)M and the binding of Ca2+ to the protein was non-co-operative. The binding of Ca2+ to protein C apparently depends on groups which ionize above pH 5.0. Ca2+ binding decreased with increased concentration of the dialysis buffer and on addition of SrCL2, MgCl2 and MnCl2 to the dialysis buffer. Digestion of protein C with trypsin or collagenase or heating of the protein to 60 degrees or 100 degrees C had little or no effect on the Ca2+ binding. Digestion of protein C with alkaline phosphatase caused a decrease in the amount of protein-bound Ca2+. This was also found for another salivary phosphoprotein, protein A. In the absence of Ca2+ the S020,w for protein C was 1.29 S and in the presence of Ca2+ it was 1.46S. Ca2+ may cause a conformational change in the protein or an aggregation of the protein molecules. No conformational changes of protein C in the presence of Ca2+ could be detected by circular dichroism or nuclear magnetic resonance.", "contents": "The binding of calcium to a salivary phosphoprotein, protein C, and comparison with calcium binding to protein A, a related salivary phosphoprotein. The binding of Ca2+ to a salivary phosphoprotein, protein C, was studied by equilibrium dialysis. In 5mM-Tris/HCl buffer, pH 7.5, protein C bound 190 nmol of Ca2+/mg of protein. The apparent dissociation constant, K, was determined to be 1.9 x 10(-4)M and the binding of Ca2+ to the protein was non-co-operative. The binding of Ca2+ to protein C apparently depends on groups which ionize above pH 5.0. Ca2+ binding decreased with increased concentration of the dialysis buffer and on addition of SrCL2, MgCl2 and MnCl2 to the dialysis buffer. Digestion of protein C with trypsin or collagenase or heating of the protein to 60 degrees or 100 degrees C had little or no effect on the Ca2+ binding. Digestion of protein C with alkaline phosphatase caused a decrease in the amount of protein-bound Ca2+. This was also found for another salivary phosphoprotein, protein A. In the absence of Ca2+ the S020,w for protein C was 1.29 S and in the presence of Ca2+ it was 1.46S. Ca2+ may cause a conformational change in the protein or an aggregation of the protein molecules. No conformational changes of protein C in the presence of Ca2+ could be detected by circular dichroism or nuclear magnetic resonance."}
{"id": "PMID:17397", "title": "The interaction of N-acetylhexosaminidase with insolubilized concanavalin A.", "content": "The specific interaction between human N-acetylhexosaminidase and concanavalin A was evaluated with respect to temperature, time, pH and concentration of specific ligand in incubation mixtures containing the enzyme and insolubilized lectin. Elution of the enzyme from insolubilized concanavalin A is dependent on both temperature and concentration of alpha-methyl mannoside. Conditions for a high yield of the enzyme from chromatography on insolubilized concanavalin A are described.", "contents": "The interaction of N-acetylhexosaminidase with insolubilized concanavalin A. The specific interaction between human N-acetylhexosaminidase and concanavalin A was evaluated with respect to temperature, time, pH and concentration of specific ligand in incubation mixtures containing the enzyme and insolubilized lectin. Elution of the enzyme from insolubilized concanavalin A is dependent on both temperature and concentration of alpha-methyl mannoside. Conditions for a high yield of the enzyme from chromatography on insolubilized concanavalin A are described."}
{"id": "PMID:17398", "title": "Purification of carboxypeptidase B from human pancreas.", "content": "Carboxypeptidase B of the human pancreas was purified by chromatography on DEAE-cellulose and CM-cellulose columns. Two forms of the enzyme, named carboxypeptidase B1 and B2, were separated. They have similar mol.wts. (34250 +/- 590) as established by polyacrylamide-gel disc electrophoresis and by gel filtration. Carboxypeptidase B2 migrates further towards the anode in disc electrophoresis. When the amino acid content of the enzymes was analysed, carboxypeptidase B2 had four more glycine and three more aspartic acid residues than had form B1. The amino acid sequence of the human carboxypeptidase B1 differs from that of the bovine enzyme only in two places in the N-terminal 20-amino-acid sequence. The N-terminal amino acid in carboxypeptidase B1 and B2 is alanine. The peptide 'map' of the tryptic digest of carboxypeptidase B1 contained more peptides than did that of form B2. The Km, the Vmax. and the pH optimum of the cleavage of the peptide substrate hippurylarginine and the ester substrate hippurylargininic acid were similar for both enzymes. CoCl2 accelerated the peptidase activity, and cadmium acetate enhanced the esterase activity, of human carboxypeptidases B1 and B2. Urea and sodium dodecyl sulphate inhibited the enzymes.", "contents": "Purification of carboxypeptidase B from human pancreas. Carboxypeptidase B of the human pancreas was purified by chromatography on DEAE-cellulose and CM-cellulose columns. Two forms of the enzyme, named carboxypeptidase B1 and B2, were separated. They have similar mol.wts. (34250 +/- 590) as established by polyacrylamide-gel disc electrophoresis and by gel filtration. Carboxypeptidase B2 migrates further towards the anode in disc electrophoresis. When the amino acid content of the enzymes was analysed, carboxypeptidase B2 had four more glycine and three more aspartic acid residues than had form B1. The amino acid sequence of the human carboxypeptidase B1 differs from that of the bovine enzyme only in two places in the N-terminal 20-amino-acid sequence. The N-terminal amino acid in carboxypeptidase B1 and B2 is alanine. The peptide 'map' of the tryptic digest of carboxypeptidase B1 contained more peptides than did that of form B2. The Km, the Vmax. and the pH optimum of the cleavage of the peptide substrate hippurylarginine and the ester substrate hippurylargininic acid were similar for both enzymes. CoCl2 accelerated the peptidase activity, and cadmium acetate enhanced the esterase activity, of human carboxypeptidases B1 and B2. Urea and sodium dodecyl sulphate inhibited the enzymes."}
{"id": "PMID:17399", "title": "[19F]fluorine nuclear-magnetic-resonance study of the interaction of difluoro-oxaloacetate with aspartate transaminase.", "content": "Difluoro-oxaloacetate interacts with the aldimine form of aspartate transaminase to give a complex, the dissociation constant of which has been determined spectrophotometrically and by 19F n.m.r. (nuclear magnetic resonance). The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of the aldimine form of the enzyme both show inflexion points in the pH5 and pH8 regions, which may arise from variations in the binding of difluoro-oxaloacetate as specific groups on the enzyme are successively protonated. Difluoro-oxaloacetate also interacts with apoenzyme to form a complex, the dissociation constant of which was determined by 19F n.m.r. The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of apoenzyme show a single inflexion point in the region of pH8. The absence, in this case, of an inflexion in the pH5 region indicates that the latter, present in the corresponding profiles for the aldimine form of the enzyme, results from ionization of an enzyme group associated with the pyridoxal phosphate cofactor.", "contents": "[19F]fluorine nuclear-magnetic-resonance study of the interaction of difluoro-oxaloacetate with aspartate transaminase. Difluoro-oxaloacetate interacts with the aldimine form of aspartate transaminase to give a complex, the dissociation constant of which has been determined spectrophotometrically and by 19F n.m.r. (nuclear magnetic resonance). The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of the aldimine form of the enzyme both show inflexion points in the pH5 and pH8 regions, which may arise from variations in the binding of difluoro-oxaloacetate as specific groups on the enzyme are successively protonated. Difluoro-oxaloacetate also interacts with apoenzyme to form a complex, the dissociation constant of which was determined by 19F n.m.r. The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of apoenzyme show a single inflexion point in the region of pH8. The absence, in this case, of an inflexion in the pH5 region indicates that the latter, present in the corresponding profiles for the aldimine form of the enzyme, results from ionization of an enzyme group associated with the pyridoxal phosphate cofactor."}
{"id": "PMID:17400", "title": "The chemistry of the collagen cross-links. Characterization of the products of reduction of skin, tendon and bone with sodium cyanoborohydride.", "content": "Reduction of tissues with sodium cyanoborohydride at pH7.4 gave results identical with those obtained by KBH4 treatment. On reduction with sodium cyanoborohydride at pH 4.4, however, a previously undetected basic compound was formed and was identified by mass spectrometry and chemical degradation techniques as dihydrohydroxymerodesmosine. Histidino-hydroxymerodesmosine was not present, and further analysis confirmed that reduced aldol, a mojor product of reduction with KBH4 at the lower pH, was also absent. These results, together with an analysis of the time course of the reduction, support previous assertions that histidino-hydroxymerodesmosine is an artifact [robins *Bailey (1973) Biochem. J. 135, 657-665] and suggests that the non-reduced form of hydroxymerodesmosine probably does not constitute a major intermolecular bond in vivo.", "contents": "The chemistry of the collagen cross-links. Characterization of the products of reduction of skin, tendon and bone with sodium cyanoborohydride. Reduction of tissues with sodium cyanoborohydride at pH7.4 gave results identical with those obtained by KBH4 treatment. On reduction with sodium cyanoborohydride at pH 4.4, however, a previously undetected basic compound was formed and was identified by mass spectrometry and chemical degradation techniques as dihydrohydroxymerodesmosine. Histidino-hydroxymerodesmosine was not present, and further analysis confirmed that reduced aldol, a mojor product of reduction with KBH4 at the lower pH, was also absent. These results, together with an analysis of the time course of the reduction, support previous assertions that histidino-hydroxymerodesmosine is an artifact [robins *Bailey (1973) Biochem. J. 135, 657-665] and suggests that the non-reduced form of hydroxymerodesmosine probably does not constitute a major intermolecular bond in vivo."}
{"id": "PMID:17401", "title": "Characterization of microsomal choloyl-coenzyme A synthetase.", "content": "Choloyl-CoA synthetase (EC 6.2.1.7) was characterized for the first time under appropriated assay conditions. The p/ optimum for the reaction is pH 7.2.-7.3. The reaction has an absolute requirement for bivalent cation. Several different metal ions fulfil this requirement, but Mn2+ and Mg2+ were the most effective. The KAppm (apparent Km) for CoA, extrapolated from kinetic data, is 50 micronM, but in fact the rate of reaction is increased little by concentrations of CoA above 25 micronM. The KAppm for ATP is 600 micronM. High concentrations of ATP appear to cause substrate inhibition. The KAppm for cholate was 6 micronM. The enzyme was inhibited by treating the microsomal fraction with N-ethylmaleimide. The inclusion of various conjugated and unconjugated bile salts in the assay also inhibited the enzyme. Unconjugated bile salts were more potent inhibitors than the conjugated bile salts. High concentrations of oleic acid inhibited the enzyme. The properties of choloyl-CoA synthetase were not modified by alterations of the properties of the lipid phase of the microsomal membrane. Treatment with phospholipase A did not alter activity directly. Triton N-101 and Triton X-100 also were without effect on activity, and the enzyme was insensitive to temperature-induced phase transitions within the lipid portion of the membrane. The enzyme can be solubilized from the microsomal membrane in an active form by treatment with Triton N-101.", "contents": "Characterization of microsomal choloyl-coenzyme A synthetase. Choloyl-CoA synthetase (EC 6.2.1.7) was characterized for the first time under appropriated assay conditions. The p/ optimum for the reaction is pH 7.2.-7.3. The reaction has an absolute requirement for bivalent cation. Several different metal ions fulfil this requirement, but Mn2+ and Mg2+ were the most effective. The KAppm (apparent Km) for CoA, extrapolated from kinetic data, is 50 micronM, but in fact the rate of reaction is increased little by concentrations of CoA above 25 micronM. The KAppm for ATP is 600 micronM. High concentrations of ATP appear to cause substrate inhibition. The KAppm for cholate was 6 micronM. The enzyme was inhibited by treating the microsomal fraction with N-ethylmaleimide. The inclusion of various conjugated and unconjugated bile salts in the assay also inhibited the enzyme. Unconjugated bile salts were more potent inhibitors than the conjugated bile salts. High concentrations of oleic acid inhibited the enzyme. The properties of choloyl-CoA synthetase were not modified by alterations of the properties of the lipid phase of the microsomal membrane. Treatment with phospholipase A did not alter activity directly. Triton N-101 and Triton X-100 also were without effect on activity, and the enzyme was insensitive to temperature-induced phase transitions within the lipid portion of the membrane. The enzyme can be solubilized from the microsomal membrane in an active form by treatment with Triton N-101."}
{"id": "PMID:17411", "title": "Chronic nondestructive arthritis associated with cutaneous polyarteritis.", "content": "Two patients with arthritis of the knee joints associated with cutaneous polyarteritis have been followed for 20 and 5 years. The arthritis is characterized by mild to moderate pain and stiffness and inflammatory joint effusions with predominantly polymorphonuclear leukocytes. Despite its chronicity, there has been no clinical or radiologic evidence of joint destruction. Necrotizing inflammation was seen in arteries of the deep skin but not in the small vessels observed in the synovial biopsy specimens.", "contents": "Chronic nondestructive arthritis associated with cutaneous polyarteritis. Two patients with arthritis of the knee joints associated with cutaneous polyarteritis have been followed for 20 and 5 years. The arthritis is characterized by mild to moderate pain and stiffness and inflammatory joint effusions with predominantly polymorphonuclear leukocytes. Despite its chronicity, there has been no clinical or radiologic evidence of joint destruction. Necrotizing inflammation was seen in arteries of the deep skin but not in the small vessels observed in the synovial biopsy specimens."}
{"id": "PMID:17412", "title": "Arthritis rounds. Pneumocystis carinii associated with polyarteritis and immunosuppressive therapy.", "content": "Pneumocystis carinii characteristically causes pneumonia in patients with immunodeficiency disorders. It occurs most often in patients with malignancy or renal transplants whose immune response has been suppressed by corticosteroids or cytotoxic agents. Individuals with connective tissue disease who receive immunosuppressive drugs become susceptible to Pneumocystis. The incidence of Pneumocystis infection in connective tissue disease is low but may increase if immunosuppressive drugs are used more often. Our patient acquired Pneumocystis pneumonia after immunosuppressive therapy for polyarteritis nodosa. Prompt recognition of this condition is essential now that specific therapy is available. Untreated Pneumocystis infection is usually fatal.", "contents": "Arthritis rounds. Pneumocystis carinii associated with polyarteritis and immunosuppressive therapy. Pneumocystis carinii characteristically causes pneumonia in patients with immunodeficiency disorders. It occurs most often in patients with malignancy or renal transplants whose immune response has been suppressed by corticosteroids or cytotoxic agents. Individuals with connective tissue disease who receive immunosuppressive drugs become susceptible to Pneumocystis. The incidence of Pneumocystis infection in connective tissue disease is low but may increase if immunosuppressive drugs are used more often. Our patient acquired Pneumocystis pneumonia after immunosuppressive therapy for polyarteritis nodosa. Prompt recognition of this condition is essential now that specific therapy is available. Untreated Pneumocystis infection is usually fatal."}
{"id": "PMID:17413", "title": "[Influence of antirheumatic phenylacetic acid derivatives on glycosaminoglycan metabolism of fibroblast culture (author's transl)].", "content": "Murine embryonic fibroblast monolayer cultures were used to study the influence of the antirheumatic phenylacetic acid derivatives ibufanac, ibuprofen, alclofenac and bufexamac and of phenylbutazone as a reference compound on glycosaminoglycan (GAG) metabolism viability and multiplication of cells cultured in vitro. The phenylacetic acid derivatives as well as phenylbutazone showed in concentrations between 10(-3) and 10(-5) M a significant inhibitory effect on GAG production and in concentrations between 10(-3) and 3.3 X 10(-4) M a cytostatic effect; bufexamac was cytostatically active up to the concentration of 10(-5) M. Ibufenac, ibuprofen and alclofenac exhibited a similar behaviour as other non-steroidal antirheumatic drugs regarding their influence of GAG metabolism and on cell multiplication.", "contents": "[Influence of antirheumatic phenylacetic acid derivatives on glycosaminoglycan metabolism of fibroblast culture (author's transl)]. Murine embryonic fibroblast monolayer cultures were used to study the influence of the antirheumatic phenylacetic acid derivatives ibufanac, ibuprofen, alclofenac and bufexamac and of phenylbutazone as a reference compound on glycosaminoglycan (GAG) metabolism viability and multiplication of cells cultured in vitro. The phenylacetic acid derivatives as well as phenylbutazone showed in concentrations between 10(-3) and 10(-5) M a significant inhibitory effect on GAG production and in concentrations between 10(-3) and 3.3 X 10(-4) M a cytostatic effect; bufexamac was cytostatically active up to the concentration of 10(-5) M. Ibufenac, ibuprofen and alclofenac exhibited a similar behaviour as other non-steroidal antirheumatic drugs regarding their influence of GAG metabolism and on cell multiplication."}
{"id": "PMID:17414", "title": "[Treatment of coronary insufficiency with beta-receptor antagonists (author's transl)].", "content": "The pathophysiology of the coronary insufficiency, the effect of beta-receptor antagonists, the understanding of these effects on the basis of the pathophysiology and the possibilities of testing beta-receptor antagonists in patients with coronary insufficiency are discussed. It is pointed out that the pathophysiology of the coronary insufficiency is based on the difference between oxygen demand of and oxygen supply to the myocardium. beta-Receptor antagonists compensate for this difference. Testing beta-receptor antagonists should include tolerance to exercise and controlled studies using standard medication for comparison.", "contents": "[Treatment of coronary insufficiency with beta-receptor antagonists (author's transl)]. The pathophysiology of the coronary insufficiency, the effect of beta-receptor antagonists, the understanding of these effects on the basis of the pathophysiology and the possibilities of testing beta-receptor antagonists in patients with coronary insufficiency are discussed. It is pointed out that the pathophysiology of the coronary insufficiency is based on the difference between oxygen demand of and oxygen supply to the myocardium. beta-Receptor antagonists compensate for this difference. Testing beta-receptor antagonists should include tolerance to exercise and controlled studies using standard medication for comparison."}
{"id": "PMID:17416", "title": "[Quantitative parameters of sympatho-neuronal and sympatho-adrenal activities in man. The influence of beta-receptor blocking agents (author's transl)].", "content": "Determination of both catecholamine concentrations (norepinephrine and epinephrine) and the activity of dopamine-beta-hydroxylase in the plasma of health volunteers and hypertensive patients leads to the conclusion that these parameters used together can be considered an index for sympathetic neuronal activity. However, highly specific and sensitive radiometric methods are necessary for the measurement of these biochemical parameters. In healthy volunteers and hypertensive patients after acute and chronic administration of beta-adrenergic blocking agents, e.g., propranolol, practolol or penbutolol, a significantly higher increase of catecholamine concentrations in the plasma has been observed during physical exercise. This pronounced increase in plasma catecholamine concentrations (mainly norepinephrine) is probably due to an enhanced compensatory sympathetic neuronal activity, accompanied by an increased peripheral resistance; this is obviously necessary in order to maintain a sufficient perfusion of peripheral tissues during work load under the influence of beta-adrenergic blocking agents, since an adequate cardiac output is prohibited by blockade of adrenergic beta-receptors. On the other hand, the pronounced increase in sympathetic tone after beta-blockade, especially after administration of high doses, could be responsible for certain reported side effects, such as hypertensive crisis in psychiatric patients or in patients with phaeochromocytoma.", "contents": "[Quantitative parameters of sympatho-neuronal and sympatho-adrenal activities in man. The influence of beta-receptor blocking agents (author's transl)]. Determination of both catecholamine concentrations (norepinephrine and epinephrine) and the activity of dopamine-beta-hydroxylase in the plasma of health volunteers and hypertensive patients leads to the conclusion that these parameters used together can be considered an index for sympathetic neuronal activity. However, highly specific and sensitive radiometric methods are necessary for the measurement of these biochemical parameters. In healthy volunteers and hypertensive patients after acute and chronic administration of beta-adrenergic blocking agents, e.g., propranolol, practolol or penbutolol, a significantly higher increase of catecholamine concentrations in the plasma has been observed during physical exercise. This pronounced increase in plasma catecholamine concentrations (mainly norepinephrine) is probably due to an enhanced compensatory sympathetic neuronal activity, accompanied by an increased peripheral resistance; this is obviously necessary in order to maintain a sufficient perfusion of peripheral tissues during work load under the influence of beta-adrenergic blocking agents, since an adequate cardiac output is prohibited by blockade of adrenergic beta-receptors. On the other hand, the pronounced increase in sympathetic tone after beta-blockade, especially after administration of high doses, could be responsible for certain reported side effects, such as hypertensive crisis in psychiatric patients or in patients with phaeochromocytoma."}
{"id": "PMID:17417", "title": "[Problems of combined therapy with cardiac glycosides and anti-anginal drugs (author's transl)].", "content": "The rational use of cardiac glycosides and anti-anginal drugs is deduced on the basis of the pathophysiological interdependence between cardiac and coronary insufficiency. With respect to therapeutic influence on myocardial function and oxygen balance the following rules ought to be regarded: 1. The use of cardiac glycosides should be restricted to patients with cardiac insufficiency in which these drugs are able to reduce the myocardial oxygen consumption due to the hemodynamic consquences of the positive-inotropic action. 2. Organic nitrates and/or beta-receptor blocking agents are compatible with simultaneous cardiac glycoside therapy, but both must be applied according to the individual requirement. 3. Coronary dilators are of questionable value in the therapy of coronary insufficiency, an additional advantage of a combination with cardiac glycosides still has to be proven. 4. There is no rational basis for the use of fixed combinations of these drugs, they do not allow effective and/or safe therapy.", "contents": "[Problems of combined therapy with cardiac glycosides and anti-anginal drugs (author's transl)]. The rational use of cardiac glycosides and anti-anginal drugs is deduced on the basis of the pathophysiological interdependence between cardiac and coronary insufficiency. With respect to therapeutic influence on myocardial function and oxygen balance the following rules ought to be regarded: 1. The use of cardiac glycosides should be restricted to patients with cardiac insufficiency in which these drugs are able to reduce the myocardial oxygen consumption due to the hemodynamic consquences of the positive-inotropic action. 2. Organic nitrates and/or beta-receptor blocking agents are compatible with simultaneous cardiac glycoside therapy, but both must be applied according to the individual requirement. 3. Coronary dilators are of questionable value in the therapy of coronary insufficiency, an additional advantage of a combination with cardiac glycosides still has to be proven. 4. There is no rational basis for the use of fixed combinations of these drugs, they do not allow effective and/or safe therapy."}
{"id": "PMID:17426", "title": "Pulmonary acid aspiration syndrome: should prophylaxis be routine?", "content": "The gastric contents of three groups of patients were aspirated at the beginning and end of anaesthesia. There were 62 prepared patients, 28 emergency patients untreated and 69 prepared patients who were given 15 ml of 0.3 M sodium citrate mixture at the time of premedication. In approximately 50% of both emergency and prepared patients pH of gastric contents initially suggested the risk of developing acid aspiration syndrome, had inhalation occurred. The proportion of untreated patients in whom more than 40 ml of gastric contents was present at induction and when the tracheal tube was removed were 13% and 31% respectively. The risks were greater in those undergoing upper abdominal operations. Sodium citrate, as used in this study, was shown to be an ineffective antacid. The use of Mist. magnesium trisilicate B.P. as preoperative antacid is urged strongly.", "contents": "Pulmonary acid aspiration syndrome: should prophylaxis be routine? The gastric contents of three groups of patients were aspirated at the beginning and end of anaesthesia. There were 62 prepared patients, 28 emergency patients untreated and 69 prepared patients who were given 15 ml of 0.3 M sodium citrate mixture at the time of premedication. In approximately 50% of both emergency and prepared patients pH of gastric contents initially suggested the risk of developing acid aspiration syndrome, had inhalation occurred. The proportion of untreated patients in whom more than 40 ml of gastric contents was present at induction and when the tracheal tube was removed were 13% and 31% respectively. The risks were greater in those undergoing upper abdominal operations. Sodium citrate, as used in this study, was shown to be an ineffective antacid. The use of Mist. magnesium trisilicate B.P. as preoperative antacid is urged strongly."}
{"id": "PMID:17427", "title": "Conditions for tracheal intubation following fazadinium and pancuronium.", "content": "Intubating conditions were studied in two groups of patients who received either fazadinium 1 mg/kg or pancuronium 0.1 mg/kg (group 1), or either fazadinium 0.5 mg/kg or pancuronium 0.08 mg/kg (group 2). In group 1 intubating conditions were studied at 30, 45, 60 and 75 s after injection of the relaxant drug, and in group 2 at 60 s after injection. Fazadinium provided better intubating conditions than pancuronium during the first 60 s after administration in group 1 (P less than 0.01). In group 2 there was no significant difference between the conditions provided by the two drugs.", "contents": "Conditions for tracheal intubation following fazadinium and pancuronium. Intubating conditions were studied in two groups of patients who received either fazadinium 1 mg/kg or pancuronium 0.1 mg/kg (group 1), or either fazadinium 0.5 mg/kg or pancuronium 0.08 mg/kg (group 2). In group 1 intubating conditions were studied at 30, 45, 60 and 75 s after injection of the relaxant drug, and in group 2 at 60 s after injection. Fazadinium provided better intubating conditions than pancuronium during the first 60 s after administration in group 1 (P less than 0.01). In group 2 there was no significant difference between the conditions provided by the two drugs."}
{"id": "PMID:17428", "title": "The bacteriology of skin cysts.", "content": "Thirty-nine clinically uninflamed cysts of the three most common varieties, epidermoid cysts, trichilemmal cysts and steatocystoma multiplex were removed under sterile conditions and the contents cultured under aerobic and anaerobic conditions. Seventy-three percent of epidermoid cysts grew significant numbers of organisms whereas none of the trichilemmal cysts did so. The organisms found were the common skin commensals, Staphylococcus epidermidis biotype I, anaerobic Gram positive cocci of the Gaffya type and Corynebacterium acnes Type I. This indicates that cysts which clinically have a punctum, namely epidermoid cysts, may become  colonized with surface bacteria under normal circumstances. If they become colonized with pathogenic bacteria they become inflamed, a not uncommon clinical picture. The results from patients with steatocystoma multiplex were difficult to interpret because of the small numbers of patients involved and the unusual clinical appearance they presented.", "contents": "The bacteriology of skin cysts. Thirty-nine clinically uninflamed cysts of the three most common varieties, epidermoid cysts, trichilemmal cysts and steatocystoma multiplex were removed under sterile conditions and the contents cultured under aerobic and anaerobic conditions. Seventy-three percent of epidermoid cysts grew significant numbers of organisms whereas none of the trichilemmal cysts did so. The organisms found were the common skin commensals, Staphylococcus epidermidis biotype I, anaerobic Gram positive cocci of the Gaffya type and Corynebacterium acnes Type I. This indicates that cysts which clinically have a punctum, namely epidermoid cysts, may become  colonized with surface bacteria under normal circumstances. If they become colonized with pathogenic bacteria they become inflamed, a not uncommon clinical picture. The results from patients with steatocystoma multiplex were difficult to interpret because of the small numbers of patients involved and the unusual clinical appearance they presented."}
{"id": "PMID:17429", "title": "Salazopyrin in the treatment of scleroderma.", "content": "Following reports of successful treatment of various forms of scleroderma with salazopyrin, 13 selected patients were treated, 8 with acrosclerosis, one with sclerodermatomyositis and four with generalized morphoea. No effect was observed except in two cases of generalized morphoea which were in the acute stage of spreading to involve most of body surface. These two were more or less cured. This observation seems to warrant further trials with salazopyrin in this rare but serious form of scleroderma.", "contents": "Salazopyrin in the treatment of scleroderma. Following reports of successful treatment of various forms of scleroderma with salazopyrin, 13 selected patients were treated, 8 with acrosclerosis, one with sclerodermatomyositis and four with generalized morphoea. No effect was observed except in two cases of generalized morphoea which were in the acute stage of spreading to involve most of body surface. These two were more or less cured. This observation seems to warrant further trials with salazopyrin in this rare but serious form of scleroderma."}
{"id": "PMID:17430", "title": "The effect of zinc and pH on the behaviour of delta-aminolevulinic acid dehydratase activity in baboons exposed to lead.", "content": "Four adult male baboons (Papio ursinus) were exposed to a cloud of lead oxide dust to induce changes in the status of delta-aminolevulinic acid dehydratase (ALAD). Enzyme activity fell rapidly to a steady state as blood lead levels rose above normal. Exogenous zinc was shown to activate the enzyme, and the antagonistic effect of zinc on in vivo and in vitro lead inhibition was demonstrated for baboons. In baboons not exposed to lead dust, ALAD showed an activity optimum at pH 7-1 which shifted to pH 6-8 with in vitro addition of lead. In baboons exposed to lead dust, with raised blood lead, activity optima were observed at pH 6-8 and 6-2, while the optimum at pH 7-1 was absent.", "contents": "The effect of zinc and pH on the behaviour of delta-aminolevulinic acid dehydratase activity in baboons exposed to lead. Four adult male baboons (Papio ursinus) were exposed to a cloud of lead oxide dust to induce changes in the status of delta-aminolevulinic acid dehydratase (ALAD). Enzyme activity fell rapidly to a steady state as blood lead levels rose above normal. Exogenous zinc was shown to activate the enzyme, and the antagonistic effect of zinc on in vivo and in vitro lead inhibition was demonstrated for baboons. In baboons not exposed to lead dust, ALAD showed an activity optimum at pH 7-1 which shifted to pH 6-8 with in vitro addition of lead. In baboons exposed to lead dust, with raised blood lead, activity optima were observed at pH 6-8 and 6-2, while the optimum at pH 7-1 was absent."}
{"id": "PMID:17431", "title": "Beta-adrenergic receptor blocking drugs: tear lysozyme and immunological screening for adverse reaction.", "content": "Patients who had received long-term therapy with practolol and other beta-adrenergic receptor blocking drugs were examined ophthalmologically. Tear lysozyme concentration and serum autoantibodies (antinuclear antibodies, DNA-binding antibodies and intercellular cement substance antibodies) were measured. It was found that beta-adrenergic receptor blocking drugs may have a pharmacological effect on the lachrymal glands, but this was not associated with dry eyes or adverse reaction. Practolol was found to be capable of reducing tear lysozyme concentrations to very low levels, and  this was initially associated with high titres of ICC antibody. No other drug tested produced these effects.", "contents": "Beta-adrenergic receptor blocking drugs: tear lysozyme and immunological screening for adverse reaction. Patients who had received long-term therapy with practolol and other beta-adrenergic receptor blocking drugs were examined ophthalmologically. Tear lysozyme concentration and serum autoantibodies (antinuclear antibodies, DNA-binding antibodies and intercellular cement substance antibodies) were measured. It was found that beta-adrenergic receptor blocking drugs may have a pharmacological effect on the lachrymal glands, but this was not associated with dry eyes or adverse reaction. Practolol was found to be capable of reducing tear lysozyme concentrations to very low levels, and  this was initially associated with high titres of ICC antibody. No other drug tested produced these effects."}
{"id": "PMID:17432", "title": "[Study of properties of NADP malate dehydrogenase from corn leaves].", "content": "Kinetic properties of purified chloroplast isoenzyme of the \"malic\" enzyme from corn leaves were studied. The enzyme had optimum activity at pH 8.0 and 36 degrees C. Under standart conditions the Michaelis constants for the \"malic\" enzyme with Mn2+ as cofactor are 0.091 mM for malate and 0.04 mM for NADP. In case of Mg2+ as cofactor they are 0.66 and 0.02 mM respectively. Respective Km values for the cofactors Mn2+ and Mg2+ are 0.018 and 0.091 mM. The activity of the \"malic\" enzyme was inhibited by reduced NADP and NAD, ATP, ADP, fructose-1,6-diphosphate, oxaloacetic, oxalic, glyoxylic, glycolic and alpha-ketoglutaric acids, as well as by phosphate anions and pyrophosphate. The inhibitory effect of all metabolites and ions is more pronounced in case of Mn, rather than Mg, used as cofactors for the reaction. A possibility of metabolic regulation of NADP-\"malic\" enzyme activity in the leaves of C4-plants, is discussed.", "contents": "[Study of properties of NADP malate dehydrogenase from corn leaves]. Kinetic properties of purified chloroplast isoenzyme of the \"malic\" enzyme from corn leaves were studied. The enzyme had optimum activity at pH 8.0 and 36 degrees C. Under standart conditions the Michaelis constants for the \"malic\" enzyme with Mn2+ as cofactor are 0.091 mM for malate and 0.04 mM for NADP. In case of Mg2+ as cofactor they are 0.66 and 0.02 mM respectively. Respective Km values for the cofactors Mn2+ and Mg2+ are 0.018 and 0.091 mM. The activity of the \"malic\" enzyme was inhibited by reduced NADP and NAD, ATP, ADP, fructose-1,6-diphosphate, oxaloacetic, oxalic, glyoxylic, glycolic and alpha-ketoglutaric acids, as well as by phosphate anions and pyrophosphate. The inhibitory effect of all metabolites and ions is more pronounced in case of Mn, rather than Mg, used as cofactors for the reaction. A possibility of metabolic regulation of NADP-\"malic\" enzyme activity in the leaves of C4-plants, is discussed."}
{"id": "PMID:17433", "title": "[Inhibition of 4-aminobutyrate transaminase by ethanolamine-O-sulfate].", "content": "The analysis of the interaction of ethanolamine-O-sulphate with 4-aminobutyrate transaminase revealed that the inhibitory effect is exerted upon the substrate subsite of the active site of the enzyme in aldimine form. The inhibition in irreversible. The inactivation rate versus pH-curve was shown to have a sigmoid character with inclination point at neutral pH. The study of inhibition kinetics by the Kitz and Wilson method revealed a complex inhibitory pattern compatible with a minimal two-step mechanism. Rate constant of inactivation was found to be equal to 0.22 min-1 and the value of the inhibitory constant--to 1.1-10(-2) M.", "contents": "[Inhibition of 4-aminobutyrate transaminase by ethanolamine-O-sulfate]. The analysis of the interaction of ethanolamine-O-sulphate with 4-aminobutyrate transaminase revealed that the inhibitory effect is exerted upon the substrate subsite of the active site of the enzyme in aldimine form. The inhibition in irreversible. The inactivation rate versus pH-curve was shown to have a sigmoid character with inclination point at neutral pH. The study of inhibition kinetics by the Kitz and Wilson method revealed a complex inhibitory pattern compatible with a minimal two-step mechanism. Rate constant of inactivation was found to be equal to 0.22 min-1 and the value of the inhibitory constant--to 1.1-10(-2) M."}
{"id": "PMID:17434", "title": "[Possible role of acetyl-CoA-carboxylase in biosynthesis of mevalonic acid and sterols in rat liver].", "content": "Effect of citrate on acetyl-CoA incorporation into mevalonic acid, sterols and fatty acids after preliminary incubation of rat liver extracts under conditions optimal for acetyl-CoA carboxylase activation, was studied. 30 min preincubation with the citrate at 37 degrees C results in a 2--3-fold stimulation of the mevalonic acid biosynthesis from acetyl-CoA in the microsomal and soluble (140 000 g) fraction, and in that of sterols precipitated by digitonin or isolated by TLC in the mitochondria--free fraction. 2-14C-malonyl-CoA incorporation into the mevalonic acid and sterols and biosynthesis of sterols from 2-14C-mevalonic acid were not stimulated under those conditions. A correlation was shown to exist between the activity of acetyl-CoA carboxylase and the rate of acetyl-CoA incorporation into mevalonate and sterols; the activity of beta-hydroxy-beta-methylglutaryl-CoA reductase, limiting the rate of the sterol biosynthesis, was not changed. The stimulating effect of citrate was found to depend on the concentration of acetyl-CoA and NADPH in the medium. The data obtained suggest that the mevalonic acid biosynthesis in rat liver may occur in the presence of acetyl-CoA carboxylase through the formation of malonyl-CoA.", "contents": "[Possible role of acetyl-CoA-carboxylase in biosynthesis of mevalonic acid and sterols in rat liver]. Effect of citrate on acetyl-CoA incorporation into mevalonic acid, sterols and fatty acids after preliminary incubation of rat liver extracts under conditions optimal for acetyl-CoA carboxylase activation, was studied. 30 min preincubation with the citrate at 37 degrees C results in a 2--3-fold stimulation of the mevalonic acid biosynthesis from acetyl-CoA in the microsomal and soluble (140 000 g) fraction, and in that of sterols precipitated by digitonin or isolated by TLC in the mitochondria--free fraction. 2-14C-malonyl-CoA incorporation into the mevalonic acid and sterols and biosynthesis of sterols from 2-14C-mevalonic acid were not stimulated under those conditions. A correlation was shown to exist between the activity of acetyl-CoA carboxylase and the rate of acetyl-CoA incorporation into mevalonate and sterols; the activity of beta-hydroxy-beta-methylglutaryl-CoA reductase, limiting the rate of the sterol biosynthesis, was not changed. The stimulating effect of citrate was found to depend on the concentration of acetyl-CoA and NADPH in the medium. The data obtained suggest that the mevalonic acid biosynthesis in rat liver may occur in the presence of acetyl-CoA carboxylase through the formation of malonyl-CoA."}
{"id": "PMID:17435", "title": "[Study of betacyanin-discolorating enzyme].", "content": "An enzyme catalyzing the discoloration and breakdown of betacyanins was isolated from beet roots Beta vulgaris by centrifugation in sucrose density gradient (2.5 M, 2.0 M, 1.5 M, 1.0 M, tris-HCl buffer, 0.05 M, pH 7.2), and purified 100-fold. The enzyme activity induced the discoloration of betanin, betanidin. It was found that the beet root enzyme exists in an insoluble state and is firmly bound with subcellular structures, which were isolated by centrifugation in sucrose gradient. The optimal activity of the enzyme was observed at pH 3.4, +40 degrees C. The dependence of the enzymatic reaction on the enzyme concentration showed a linearity. Studies of the enzyme inhibition by sodium azide, sodium diethyldithiocarbamate, thiourea, demonstrated that the active site of the enzyme contains a metal. The enzymatic discoloration of betanin is followed by the oxygen uptake.", "contents": "[Study of betacyanin-discolorating enzyme]. An enzyme catalyzing the discoloration and breakdown of betacyanins was isolated from beet roots Beta vulgaris by centrifugation in sucrose density gradient (2.5 M, 2.0 M, 1.5 M, 1.0 M, tris-HCl buffer, 0.05 M, pH 7.2), and purified 100-fold. The enzyme activity induced the discoloration of betanin, betanidin. It was found that the beet root enzyme exists in an insoluble state and is firmly bound with subcellular structures, which were isolated by centrifugation in sucrose gradient. The optimal activity of the enzyme was observed at pH 3.4, +40 degrees C. The dependence of the enzymatic reaction on the enzyme concentration showed a linearity. Studies of the enzyme inhibition by sodium azide, sodium diethyldithiocarbamate, thiourea, demonstrated that the active site of the enzyme contains a metal. The enzymatic discoloration of betanin is followed by the oxygen uptake."}
{"id": "PMID:17436", "title": "The turnover rate of gamma-aminobutyric acid in the nuclei of telencephalon: implications in the pharmacology of antipsychotics and of a minor tranquilizer.", "content": "The turnover rate of GABA is measured in substantia nigra, globus pallidus, N. accumbens, and striatum of rats injected with muscimol, a potent GABA agonist, and diazepam. The similarity of action of the two drugs on GABA turnover further supports the theory that diazepam acts as a GABA-mimetic drug. Haloperidol and clozapine affect GABA turnover differently in different nuclei. Haloperidol decreases GABA turnover in caudate but does not affect that in substantia nigra, whereas clozapine increases GABA turnover in both areas. However, both drugs accelerate GABA turnover in globus pallidus and N. accumbens. It is suggested that an increase of GABA turnover and perhaps of GABA release in striatum and substantia nigra may account for the lack of tardive dyskinesia and extrapyramidal side effects of clozapine.", "contents": "The turnover rate of gamma-aminobutyric acid in the nuclei of telencephalon: implications in the pharmacology of antipsychotics and of a minor tranquilizer. The turnover rate of GABA is measured in substantia nigra, globus pallidus, N. accumbens, and striatum of rats injected with muscimol, a potent GABA agonist, and diazepam. The similarity of action of the two drugs on GABA turnover further supports the theory that diazepam acts as a GABA-mimetic drug. Haloperidol and clozapine affect GABA turnover differently in different nuclei. Haloperidol decreases GABA turnover in caudate but does not affect that in substantia nigra, whereas clozapine increases GABA turnover in both areas. However, both drugs accelerate GABA turnover in globus pallidus and N. accumbens. It is suggested that an increase of GABA turnover and perhaps of GABA release in striatum and substantia nigra may account for the lack of tardive dyskinesia and extrapyramidal side effects of clozapine."}
{"id": "PMID:17437", "title": "The actions of amphetamine on neurotransmitters: a brief review.", "content": "The central stimulant actions of d-amphetamine are not altered in animals in which brain stores of catecholamines have been depleted with reserpine, but they are blocked by alpha-methyltyrosine, which inhibits catecholamine synthesis. The results of a variety of experiments suggest that the central actions of amphetamine result primarily from the ability of the drug to facilitate the release of newly synthesized dopamine from nerve terminals in the forebrain. The results of experiments in animals in which dopaminergic nerve terminals in various brain regions have been selectively destroyed by intracranial microinjection of 6-hydroxydopamine reveal that the locomotor stimulant actions of relatively low doses of amphetamine are dependent upon mesolimbic dopaminergic neurons, whereas the stereotyped behaviors induced by relatively larger doses of amphetamine are dependent upon nigrostriatal dopaminergic neurons. The central actions of amphetamine appear to be the primary result of interactions with dopamine neurons, but secondarily the drug also alters the dynamics of other putative neurotransmitters (e.g. acetylcholine, 5-hydroxytryptamine) in the brain.", "contents": "The actions of amphetamine on neurotransmitters: a brief review. The central stimulant actions of d-amphetamine are not altered in animals in which brain stores of catecholamines have been depleted with reserpine, but they are blocked by alpha-methyltyrosine, which inhibits catecholamine synthesis. The results of a variety of experiments suggest that the central actions of amphetamine result primarily from the ability of the drug to facilitate the release of newly synthesized dopamine from nerve terminals in the forebrain. The results of experiments in animals in which dopaminergic nerve terminals in various brain regions have been selectively destroyed by intracranial microinjection of 6-hydroxydopamine reveal that the locomotor stimulant actions of relatively low doses of amphetamine are dependent upon mesolimbic dopaminergic neurons, whereas the stereotyped behaviors induced by relatively larger doses of amphetamine are dependent upon nigrostriatal dopaminergic neurons. The central actions of amphetamine appear to be the primary result of interactions with dopamine neurons, but secondarily the drug also alters the dynamics of other putative neurotransmitters (e.g. acetylcholine, 5-hydroxytryptamine) in the brain."}
{"id": "PMID:17439", "title": "Effect of heparin on complement activation and lysis of paroxysmal nocturnal hemoglobinuria (PNH) red cells.", "content": "The effect of heparin upon the binding of the third component of complement (C3) to PNH red cells in vitro and their subsequent hemolysis is described. Heparin, in increasing concentrations, progressively inhibits membrane C3 fixation and hemolysis when the classic complement pathway is activated by anti-red cell antibodies. Heparin has a biphasic effect upon membrane C3 fixation and hemolysis when complement is activated in serum at decreased ionic strength (sucrose lysis) or in serum at decreased pH (Ham test). Heparin in concentrations above 2 U/ml inhibits C3 binding and hemolysis while lower concentrations of heparin enhance the consequences of complement activation by these two procedures. This enhanced complement activation may explain the increased hemolysis sometimes reported in PNH patients treated with heparin, and suggests that heparin may aggravate the consequences of pathologic alternative pathway complement activation in other diseases.", "contents": "Effect of heparin on complement activation and lysis of paroxysmal nocturnal hemoglobinuria (PNH) red cells. The effect of heparin upon the binding of the third component of complement (C3) to PNH red cells in vitro and their subsequent hemolysis is described. Heparin, in increasing concentrations, progressively inhibits membrane C3 fixation and hemolysis when the classic complement pathway is activated by anti-red cell antibodies. Heparin has a biphasic effect upon membrane C3 fixation and hemolysis when complement is activated in serum at decreased ionic strength (sucrose lysis) or in serum at decreased pH (Ham test). Heparin in concentrations above 2 U/ml inhibits C3 binding and hemolysis while lower concentrations of heparin enhance the consequences of complement activation by these two procedures. This enhanced complement activation may explain the increased hemolysis sometimes reported in PNH patients treated with heparin, and suggests that heparin may aggravate the consequences of pathologic alternative pathway complement activation in other diseases."}
{"id": "PMID:17440", "title": "Metabolic crowding effect in suspension of cultured lymphocytes.", "content": "We studied the respiration and glucose utilization of suspensions of cultured lymphocytes. Respiration was measured by a couloximetric method using closed systems without a gas-suspension interface. The sensitivity of the method allowed measurements during a time interval of less than 1 hr. We found that the respiration of lymphocytes was strongly density dependent over the range of 10(8)-10(3) cells/ml. Oxygen utilization per cell increased 100-fold with 1000-fold dilution of the cell suspension. Glucose utilization showed little density dependence. We showed that the phenomenon was not due to nutrient depletion, pH shifts, accumulation of lactic acid, nor damage of cells during the dilution. Since in our experiments a gas-liquid interface was absent, the previously suggested explanation of gas diffusion as a limiting factor has been excluded. The experiment was best explained by regulation of respiration by humoral factors produced by the cell suspension.", "contents": "Metabolic crowding effect in suspension of cultured lymphocytes. We studied the respiration and glucose utilization of suspensions of cultured lymphocytes. Respiration was measured by a couloximetric method using closed systems without a gas-suspension interface. The sensitivity of the method allowed measurements during a time interval of less than 1 hr. We found that the respiration of lymphocytes was strongly density dependent over the range of 10(8)-10(3) cells/ml. Oxygen utilization per cell increased 100-fold with 1000-fold dilution of the cell suspension. Glucose utilization showed little density dependence. We showed that the phenomenon was not due to nutrient depletion, pH shifts, accumulation of lactic acid, nor damage of cells during the dilution. Since in our experiments a gas-liquid interface was absent, the previously suggested explanation of gas diffusion as a limiting factor has been excluded. The experiment was best explained by regulation of respiration by humoral factors produced by the cell suspension."}
{"id": "PMID:17441", "title": "Influence of H+ on K+ on adenosine-induced dilatation at pial arteries of cats.", "content": "The influence of changes in the perivascular K+ and H+ concentrations upon adenosine-induced dilatations of pial arteries was investigated by localized perivascular application using micropuncture technique. Adenosine (10(-9)-10(-3) M) was dissolved in mock spinal fluids with varying bicarbonate and potassium concentrations (5 and 22 mM HCO3-, and 6 and 10 mM K+). Concentration response curves revealed that adenosine induced the same change in pial arterial diameter when dissolved either in an inert (11 mM HCO3-) or in a constrictory (22 mM HCO3-) mock spinal fluid. However, adenosine, when dissolved in a more acidic or higher potassium-containing solution (5 mM HCO3-, or 6 or 10 mM K+) produced a diminished dilatatory effect. It is concluded that, for a quantification of the individual contributions of several metabolic factors in the regulation of vascular resistance, it is necessary to consider their interactions.", "contents": "Influence of H+ on K+ on adenosine-induced dilatation at pial arteries of cats. The influence of changes in the perivascular K+ and H+ concentrations upon adenosine-induced dilatations of pial arteries was investigated by localized perivascular application using micropuncture technique. Adenosine (10(-9)-10(-3) M) was dissolved in mock spinal fluids with varying bicarbonate and potassium concentrations (5 and 22 mM HCO3-, and 6 and 10 mM K+). Concentration response curves revealed that adenosine induced the same change in pial arterial diameter when dissolved either in an inert (11 mM HCO3-) or in a constrictory (22 mM HCO3-) mock spinal fluid. However, adenosine, when dissolved in a more acidic or higher potassium-containing solution (5 mM HCO3-, or 6 or 10 mM K+) produced a diminished dilatatory effect. It is concluded that, for a quantification of the individual contributions of several metabolic factors in the regulation of vascular resistance, it is necessary to consider their interactions."}
{"id": "PMID:17444", "title": "Observations on the behaviour of barium sulphate suspensions in gastric secretion.", "content": "A number of barium sulphate suspensions showed varying patterns of stability when provoked with gastric secretion. The stability of the suspensions was affected by the pH, the mucin content and the volume of secretion used. These studies indicate that flocculation of the suspension in the presence of gastric residue decreases as the amount of undiluted barium sulphate in the mixture is increased.", "contents": "Observations on the behaviour of barium sulphate suspensions in gastric secretion. A number of barium sulphate suspensions showed varying patterns of stability when provoked with gastric secretion. The stability of the suspensions was affected by the pH, the mucin content and the volume of secretion used. These studies indicate that flocculation of the suspension in the presence of gastric residue decreases as the amount of undiluted barium sulphate in the mixture is increased."}
{"id": "PMID:17451", "title": "Cardiovascular and sympathetic response to exercise after long-term beta-adrenergic blockade.", "content": "The response to dynamic exercise was investigated in 21 patients receiving long-term treatment with beta-adrenoceptor antagonists and 22 controls. An electrocardiogram (ECG) and blood pressure were recorded before and after treadmill exercise, and plasma dopamine-beta-hydroxylase (DBH) activity was measured as an index of changes in sympathetic activity. Heart rate and blood pressure were lower at rest and throughout exercise in treated patients, although the pressor effect of exercise was not reduced. The ECG P-R interval was lengthened, and in addition the Q-T interval was prolonged. After exercise, plasma DBH activity was significantly increased in controls but not in treated patients. We conclude that long-term administration of beta-adrenergic blockers increases myocardial repolarisation time and reduces sympathetic nervous activity. These actions may contribute to the antiarrhythmic and hypotensive effects of long-term beta-blockade.", "contents": "Cardiovascular and sympathetic response to exercise after long-term beta-adrenergic blockade. The response to dynamic exercise was investigated in 21 patients receiving long-term treatment with beta-adrenoceptor antagonists and 22 controls. An electrocardiogram (ECG) and blood pressure were recorded before and after treadmill exercise, and plasma dopamine-beta-hydroxylase (DBH) activity was measured as an index of changes in sympathetic activity. Heart rate and blood pressure were lower at rest and throughout exercise in treated patients, although the pressor effect of exercise was not reduced. The ECG P-R interval was lengthened, and in addition the Q-T interval was prolonged. After exercise, plasma DBH activity was significantly increased in controls but not in treated patients. We conclude that long-term administration of beta-adrenergic blockers increases myocardial repolarisation time and reduces sympathetic nervous activity. These actions may contribute to the antiarrhythmic and hypotensive effects of long-term beta-blockade."}
{"id": "PMID:17453", "title": "Release of a neurodepressing hormone from the crustacean sinus gland.", "content": "The nervous system of the crayfish contains a peptide of low molecular weight which depresses the spontaneous electrical activity of motoneurons in the abdominal ganglia. Most of this substance is contained in the sinus gland, a neurohemal organ in the eyestalk. Electrical stimulation of the isolated sinus gland, or its incubation in potassium-rich solutions (20--80 mM) results in the release of the neurodepressing peptide. The release is calcium-dependent and appears to involve a process of exocytosis. The released product shows electrophoretic properties undistinguishable from the substance present in the sinus gland.", "contents": "Release of a neurodepressing hormone from the crustacean sinus gland. The nervous system of the crayfish contains a peptide of low molecular weight which depresses the spontaneous electrical activity of motoneurons in the abdominal ganglia. Most of this substance is contained in the sinus gland, a neurohemal organ in the eyestalk. Electrical stimulation of the isolated sinus gland, or its incubation in potassium-rich solutions (20--80 mM) results in the release of the neurodepressing peptide. The release is calcium-dependent and appears to involve a process of exocytosis. The released product shows electrophoretic properties undistinguishable from the substance present in the sinus gland."}
{"id": "PMID:17455", "title": "The blockade of serotonin uptake into synaptosomes:relationship to an interaction with monoamine oxidase inhibitors.", "content": "To test the hypothesis that the hyperpyrexia produced by meperidine and detromethorphan in rabbits pretreated with a monoamine oxidase inhibitor is related to inhibition of neuronal uptake of serotonin (5-hydroxytryptamine (5-HT)), fluoxetine (Lilly 110140) was studied. This potent and specific 5-HT neuronal uptake blocker was administered to phenelzine-pretreated rabbits and found to produce a lethal hyperpyrexia in doses equal to or greater than 2.5 mg/kg. The order of potency in blocking 5-[14C]HT uptake into synaptosomes prepared from rabbits was: fluoxetine greater than meperidine = dextromethorphan = levorphanol greater than anileridine greater than alphaprodine greater than morphine. Since fluoxetine, meperidine, and dextromethorphan produce hyperpyrexia in phenelzine-pretreated rabbits, whereas anileridine, alphaprodine, and morphine do not, there appears to be some correlation between the hyperpyrexic response and inhibition of 5-HT uptake. The exception is levorphanol, which is not hyperpyrexic despite being equipotent with meperidine and dextromethorphan in inhibiting 5-HT uptake. The ineffectiveness of levorphanol in producing hyperpyrexia may be due to its marked depressant properties, since the addition of another depressant drug (pentobarbital) antagonized the hyperpyrexic effect of meperidine.", "contents": "The blockade of serotonin uptake into synaptosomes:relationship to an interaction with monoamine oxidase inhibitors. To test the hypothesis that the hyperpyrexia produced by meperidine and detromethorphan in rabbits pretreated with a monoamine oxidase inhibitor is related to inhibition of neuronal uptake of serotonin (5-hydroxytryptamine (5-HT)), fluoxetine (Lilly 110140) was studied. This potent and specific 5-HT neuronal uptake blocker was administered to phenelzine-pretreated rabbits and found to produce a lethal hyperpyrexia in doses equal to or greater than 2.5 mg/kg. The order of potency in blocking 5-[14C]HT uptake into synaptosomes prepared from rabbits was: fluoxetine greater than meperidine = dextromethorphan = levorphanol greater than anileridine greater than alphaprodine greater than morphine. Since fluoxetine, meperidine, and dextromethorphan produce hyperpyrexia in phenelzine-pretreated rabbits, whereas anileridine, alphaprodine, and morphine do not, there appears to be some correlation between the hyperpyrexic response and inhibition of 5-HT uptake. The exception is levorphanol, which is not hyperpyrexic despite being equipotent with meperidine and dextromethorphan in inhibiting 5-HT uptake. The ineffectiveness of levorphanol in producing hyperpyrexia may be due to its marked depressant properties, since the addition of another depressant drug (pentobarbital) antagonized the hyperpyrexic effect of meperidine."}
{"id": "PMID:17456", "title": "Multiple forms of DNA-dependent RNA and polyadenylic acid polymerases from heterotrophically grown Rhodospirillum rubrum.", "content": "Three, two major and one minor, distinct RNA polymerases have been isolated and partially purified from heterotrophically grown Rhodospirillum rubrum, a facultative photosynethetic bacterium. Associated with each of these three enzymes is a distinct polyadenylic acid polyemrase. All of these enzyme activities are dependent on DNA templates and are resistant to rifampicin and streptovaricin. The structural subunit composition, the response to various chemical compounds and DNA templates, and the properties of the products of these enzymes are studied in detail and compared with those of similar enzyme activities from other bacterial systems. Several unique features have been observed in the R. rubrum enzyme systems, such as an uneven incorporation of purine and pyrimidine nucleotides by the RNA polymerases, and the presence of a lag period in the polyadenylic acid polymerase activities.", "contents": "Multiple forms of DNA-dependent RNA and polyadenylic acid polymerases from heterotrophically grown Rhodospirillum rubrum. Three, two major and one minor, distinct RNA polymerases have been isolated and partially purified from heterotrophically grown Rhodospirillum rubrum, a facultative photosynethetic bacterium. Associated with each of these three enzymes is a distinct polyadenylic acid polyemrase. All of these enzyme activities are dependent on DNA templates and are resistant to rifampicin and streptovaricin. The structural subunit composition, the response to various chemical compounds and DNA templates, and the properties of the products of these enzymes are studied in detail and compared with those of similar enzyme activities from other bacterial systems. Several unique features have been observed in the R. rubrum enzyme systems, such as an uneven incorporation of purine and pyrimidine nucleotides by the RNA polymerases, and the presence of a lag period in the polyadenylic acid polymerase activities."}
{"id": "PMID:17457", "title": "Preenrichment procedure for detection of Salmonella in gelatin.", "content": "Trypticase soy broth was superior to nutrient and lactose broths as a preenrichment medium for the detection of Salmonella in artificially and naturally contaiminated gelatin. The detection rate for Salmonella were further enhanced when homogenization of the gelatin-broth mixture was accomplished by the use of gelatinase rather than by heating of 45 degrees C. Detection rats were also increased by adjusting the pH of the gelatin-broth mixture of 7.0, optimum pH for gelatinase (EC 3.4.23.2) activity.", "contents": "Preenrichment procedure for detection of Salmonella in gelatin. Trypticase soy broth was superior to nutrient and lactose broths as a preenrichment medium for the detection of Salmonella in artificially and naturally contaiminated gelatin. The detection rate for Salmonella were further enhanced when homogenization of the gelatin-broth mixture was accomplished by the use of gelatinase rather than by heating of 45 degrees C. Detection rats were also increased by adjusting the pH of the gelatin-broth mixture of 7.0, optimum pH for gelatinase (EC 3.4.23.2) activity."}
{"id": "PMID:17458", "title": "The cellular role of nitrogen in the biosynthesis of alkaloids by submerged culture of Claviceps purpurea (Fr.) Tul.", "content": "Asparagine was a superior nitrogen source for clavine-alkaloid production in Claviceps purpurea. Its transport into the cell excedded the cell's biosynthetic need for this amino acid. Asparagine entered the cell without degradation. This disturbed the relative pool sizes of various amino acids resulting in a change in the genetically determined ratio at which amino acids were utilized for protein synthesis. Overproduction of alkaloids (4500 mug.ml-1) may be associated with increased availability of tryptophan because of the enhanced assimilation of asparagine-derived ammonia via glutamine synthetase (EC 6.3.1.2). However, ammonium salts in the fermentation broth led to a depression of the alkaloid yield. Partial replacement of the ammonium salt by aspartic acid elevated alkaloid production.", "contents": "The cellular role of nitrogen in the biosynthesis of alkaloids by submerged culture of Claviceps purpurea (Fr.) Tul. Asparagine was a superior nitrogen source for clavine-alkaloid production in Claviceps purpurea. Its transport into the cell excedded the cell's biosynthetic need for this amino acid. Asparagine entered the cell without degradation. This disturbed the relative pool sizes of various amino acids resulting in a change in the genetically determined ratio at which amino acids were utilized for protein synthesis. Overproduction of alkaloids (4500 mug.ml-1) may be associated with increased availability of tryptophan because of the enhanced assimilation of asparagine-derived ammonia via glutamine synthetase (EC 6.3.1.2). However, ammonium salts in the fermentation broth led to a depression of the alkaloid yield. Partial replacement of the ammonium salt by aspartic acid elevated alkaloid production."}
{"id": "PMID:17459", "title": "Clostridium perfringens--specific lysin.", "content": "A mitomycin C induced lysate of Clostridium perfringens strain KZ219 was lytic to 50 strains of C. perfringens of types A-E, and three strains of C. plagarum. The lysin was active against only 2 out of 87 strains of 51 other clostridial species. The optimum pH of the lytic agent was 5.5. The activity was largely inactivated by proteolytic enzymes, and nearly completely inactivated by heating at 60 degrees C for 5 min.", "contents": "Clostridium perfringens--specific lysin. A mitomycin C induced lysate of Clostridium perfringens strain KZ219 was lytic to 50 strains of C. perfringens of types A-E, and three strains of C. plagarum. The lysin was active against only 2 out of 87 strains of 51 other clostridial species. The optimum pH of the lytic agent was 5.5. The activity was largely inactivated by proteolytic enzymes, and nearly completely inactivated by heating at 60 degrees C for 5 min."}
{"id": "PMID:17460", "title": "Effects of the herbicides fluometuron and prometryn of Rhizoctonia solani in soil cultures.", "content": "Responses of Rhizoctonia solani to herbicides in soil cultures were assessed by measuring soil enzyme activity and other growth-related factors. Both beta-galactosidase (EC 3.2.1.23) and phosphatase (EC 3.1.3.1.3.1.3.2) activities were highly correlated with amounts of mycelium in soil. Both enzyme activities were reduced significantly by either fluometuron or prometryn at 40 microgram/g of soil; the pathogen was more distinctly suppressed by fluometron and showed a stronger tendency to overcome the effects of prometryn with time. Inhibition was also reflected in reduced ultilization of glucose and less CO2-C evolved. Except for an increase in beta-galactosidase activity in the presence of 1 microgram fluometuron, low levels of either herbicide had little effect on the pathogen.", "contents": "Effects of the herbicides fluometuron and prometryn of Rhizoctonia solani in soil cultures. Responses of Rhizoctonia solani to herbicides in soil cultures were assessed by measuring soil enzyme activity and other growth-related factors. Both beta-galactosidase (EC 3.2.1.23) and phosphatase (EC 3.1.3.1.3.1.3.2) activities were highly correlated with amounts of mycelium in soil. Both enzyme activities were reduced significantly by either fluometuron or prometryn at 40 microgram/g of soil; the pathogen was more distinctly suppressed by fluometron and showed a stronger tendency to overcome the effects of prometryn with time. Inhibition was also reflected in reduced ultilization of glucose and less CO2-C evolved. Except for an increase in beta-galactosidase activity in the presence of 1 microgram fluometuron, low levels of either herbicide had little effect on the pathogen."}
{"id": "PMID:17461", "title": "Suitability of some enrichment broths and diluents for enumerating cold- and heat-stressed Vibrio parahaemolyticus.", "content": "Vibrio parahaemolyticus cells were injured by chilling and heating, and their recovery was  tested in glucose-salt-Teepol broth (GSTB), tryptic soy broth containing 7% NaCl (TSBS), Horie - arabinose - ethyl violet broth (HAEB), and water blue - alizarin yellow broth (WBAY). Exponential phase cells were more sensitive to cold shock than were stationary phase cells. Exposure of chill-injured V. parahaemolyticus to GSTB and TSBS resulted in 70 to 80% death; about 70% lethality was noted for heat-injured cells inoculated into TSBS. Neither HAEB nor WBAY enrichment media were lethal to stressed cells, although rates of growth were retarded. The 3% NaCl in 0.1 M potassium phosphate (pH 7.0) diluent proved to be most suitable for  protecting against inactivation of cold- and heat-injured cells.", "contents": "Suitability of some enrichment broths and diluents for enumerating cold- and heat-stressed Vibrio parahaemolyticus. Vibrio parahaemolyticus cells were injured by chilling and heating, and their recovery was  tested in glucose-salt-Teepol broth (GSTB), tryptic soy broth containing 7% NaCl (TSBS), Horie - arabinose - ethyl violet broth (HAEB), and water blue - alizarin yellow broth (WBAY). Exponential phase cells were more sensitive to cold shock than were stationary phase cells. Exposure of chill-injured V. parahaemolyticus to GSTB and TSBS resulted in 70 to 80% death; about 70% lethality was noted for heat-injured cells inoculated into TSBS. Neither HAEB nor WBAY enrichment media were lethal to stressed cells, although rates of growth were retarded. The 3% NaCl in 0.1 M potassium phosphate (pH 7.0) diluent proved to be most suitable for  protecting against inactivation of cold- and heat-injured cells."}
{"id": "PMID:17462", "title": "Inhibiton by sulfanilamide of sporulation in Saccharomyces cerevisiae.", "content": "The antimetabolite sulfanilamide inhibits sporulation in Saccharomyces cerevisiae strain AP1. Cells exposed to sulfanilamide at various times during the sporulation process become progressively insensitive to the drug, although accumulation of sulfanilamide by the cells increases with time. Vegetative growth of AP1 is practically unaffected by sulfanilamide; pregrowth of the cells in the presence of the drug does not prevent sporulation. Thus, inhibition is confined to the meiotic phase of the cell cycle. Sensitivity to sulfanilamide is independent of pH. Increasing the time cells are exposed to sulfanilamide results in a progressive reduction of ascus formation; however, the inhibition is reversible since sporulation can occur in cells exposed to the drug for greater than 24 h. The drug arrests the cells at a point before commitment to sporulation, since yeast cells exposed to sulfanilamide for 12 h do not complete the sporulation process when returnedto vegetative medium, but resume mitotic growth instead. Meiotic nuclear division is largely prevented by sulfanilamide, and synthesis of RNA and protein is severely retarded. DNA synthesis is inhibited up to 50%; glycogen synthesis is approximately 90% inhibited. Other yeast strains showed varying sensitivity to sulfanilamide; homothallic strains were generally less affected.", "contents": "Inhibiton by sulfanilamide of sporulation in Saccharomyces cerevisiae. The antimetabolite sulfanilamide inhibits sporulation in Saccharomyces cerevisiae strain AP1. Cells exposed to sulfanilamide at various times during the sporulation process become progressively insensitive to the drug, although accumulation of sulfanilamide by the cells increases with time. Vegetative growth of AP1 is practically unaffected by sulfanilamide; pregrowth of the cells in the presence of the drug does not prevent sporulation. Thus, inhibition is confined to the meiotic phase of the cell cycle. Sensitivity to sulfanilamide is independent of pH. Increasing the time cells are exposed to sulfanilamide results in a progressive reduction of ascus formation; however, the inhibition is reversible since sporulation can occur in cells exposed to the drug for greater than 24 h. The drug arrests the cells at a point before commitment to sporulation, since yeast cells exposed to sulfanilamide for 12 h do not complete the sporulation process when returnedto vegetative medium, but resume mitotic growth instead. Meiotic nuclear division is largely prevented by sulfanilamide, and synthesis of RNA and protein is severely retarded. DNA synthesis is inhibited up to 50%; glycogen synthesis is approximately 90% inhibited. Other yeast strains showed varying sensitivity to sulfanilamide; homothallic strains were generally less affected."}
{"id": "PMID:17463", "title": "Enzymatic hydrolysis of agar: purification and characterization of beta-neoagarotetraose hydrolase from Pseudomonas atlantica.", "content": "Agarose is degraded by a beta-agarase from Pseudomonas atlantica to neoagarooligosaccharides of degree of polymerization (DP), 4, 6, 8, and 10. A beta-neoagarotetraose hydrolase cleaves the central beta-linkage in neoagarotetraose and the beta-linkage near the nonreducing end in neoagarohexaose and -octaose to yield neoagarobiose. The beta-neoagarotetraose hydrolase was localized on or outside the cytoplasmic membrane, in the cell wall region. The enzyme was activated by NaCl, KCl, CaCl2, MnCl2, and MgSO4, has a Km of 3.4 X 10(-3) M for neoagarotetraose, was free from beta-agarase and alpha-neoagarobiose hydrolase activity, and showed no transglycosidic activity.", "contents": "Enzymatic hydrolysis of agar: purification and characterization of beta-neoagarotetraose hydrolase from Pseudomonas atlantica. Agarose is degraded by a beta-agarase from Pseudomonas atlantica to neoagarooligosaccharides of degree of polymerization (DP), 4, 6, 8, and 10. A beta-neoagarotetraose hydrolase cleaves the central beta-linkage in neoagarotetraose and the beta-linkage near the nonreducing end in neoagarohexaose and -octaose to yield neoagarobiose. The beta-neoagarotetraose hydrolase was localized on or outside the cytoplasmic membrane, in the cell wall region. The enzyme was activated by NaCl, KCl, CaCl2, MnCl2, and MgSO4, has a Km of 3.4 X 10(-3) M for neoagarotetraose, was free from beta-agarase and alpha-neoagarobiose hydrolase activity, and showed no transglycosidic activity."}
{"id": "PMID:17464", "title": "Properties of 1-phosphofructokinase from Pseudomonas putida.", "content": "The 1-phosphofructokinase (1-PFK, EC 2.7.1.56) from Pseudomonas putida was partially purified by a combination of (NH4)2SO4 fractionation and DEAE-Sephadex column chromatography. In its kinetic properties, this enzyme resembled the 1-PFK's from other bacteria. With the substrates fructose-1-phosphate (F-1-P) and adenosine triphosphate (ATP) Michaelis-Menten kinetics were observed, the Km for one substrate being unaffected by a variation in the concentration of the other substrate. At pH 8.0, the Km values for F-1-P and ATP were 1.64 X 10(-4) M and 4.08 X 10(-4) M, respectively. At fixed concentrations of F-1-P and ATP, an increase in the Mg2+ resulted in sigmoidal kinetics. Activity was inhibited by ATP when the ratio of ATP:Mg2+ was greater than 0.5 suggesting that ATP:2 Mg2+ was the substrate and free ATP was inhibitory. Activity of 1-PFK was stimulated by K+ and to a lesser extent by NH4+ and Na+. The reaction rate was unaffected by 2 mM K2HPO4, pyruvate, phosphoenolpyruvate, adenosine monophosphate, adenosine 3',5'-cyclic monophosphate, fructose-6-phosphate, glucose-6-phosphate, 6-phosphogluconate, 2-keto-3-deoxy-6-phosphogluconate, or citrate. The results indicated that the 1-PFK from P. putida was not allosterically regulated by a number of metabolites which may play an important role in the catabolism of D-fructose.", "contents": "Properties of 1-phosphofructokinase from Pseudomonas putida. The 1-phosphofructokinase (1-PFK, EC 2.7.1.56) from Pseudomonas putida was partially purified by a combination of (NH4)2SO4 fractionation and DEAE-Sephadex column chromatography. In its kinetic properties, this enzyme resembled the 1-PFK's from other bacteria. With the substrates fructose-1-phosphate (F-1-P) and adenosine triphosphate (ATP) Michaelis-Menten kinetics were observed, the Km for one substrate being unaffected by a variation in the concentration of the other substrate. At pH 8.0, the Km values for F-1-P and ATP were 1.64 X 10(-4) M and 4.08 X 10(-4) M, respectively. At fixed concentrations of F-1-P and ATP, an increase in the Mg2+ resulted in sigmoidal kinetics. Activity was inhibited by ATP when the ratio of ATP:Mg2+ was greater than 0.5 suggesting that ATP:2 Mg2+ was the substrate and free ATP was inhibitory. Activity of 1-PFK was stimulated by K+ and to a lesser extent by NH4+ and Na+. The reaction rate was unaffected by 2 mM K2HPO4, pyruvate, phosphoenolpyruvate, adenosine monophosphate, adenosine 3',5'-cyclic monophosphate, fructose-6-phosphate, glucose-6-phosphate, 6-phosphogluconate, 2-keto-3-deoxy-6-phosphogluconate, or citrate. The results indicated that the 1-PFK from P. putida was not allosterically regulated by a number of metabolites which may play an important role in the catabolism of D-fructose."}
{"id": "PMID:17465", "title": "Concentration of enteroviruses from large volumes of turbid estuary water.", "content": "A method is described for the efficient concentration of viruses from large volumes of highly turbid estuary water. Virus in acidified seawater in the presence of aluminum chloride is adsorbed to a 10-in. (about 25.4 cm) fibreglass depth cartridge and 2- and 0.65-micron epoxy-fibreglass filters in series. This filter series is capable of efficiently adsorbing enteroviruses from 50 U.S. gallons (about 190) of estuary water of varying salinity and turbidity. Adsorbed viruses were eluted from the filters with glycine buffer (pH 11.5) and the eluate reconcentrated by using a precipitate formed by the addition of ferric chloride. Viruses were eluted from this precipitate with fetal calf serum. Using this procedure, four different enteroviruses in 50 gallons (about 190) of estuary water were concentrated 9 000- to 12 000-fold with an overall efficiency of 41%.", "contents": "Concentration of enteroviruses from large volumes of turbid estuary water. A method is described for the efficient concentration of viruses from large volumes of highly turbid estuary water. Virus in acidified seawater in the presence of aluminum chloride is adsorbed to a 10-in. (about 25.4 cm) fibreglass depth cartridge and 2- and 0.65-micron epoxy-fibreglass filters in series. This filter series is capable of efficiently adsorbing enteroviruses from 50 U.S. gallons (about 190) of estuary water of varying salinity and turbidity. Adsorbed viruses were eluted from the filters with glycine buffer (pH 11.5) and the eluate reconcentrated by using a precipitate formed by the addition of ferric chloride. Viruses were eluted from this precipitate with fetal calf serum. Using this procedure, four different enteroviruses in 50 gallons (about 190) of estuary water were concentrated 9 000- to 12 000-fold with an overall efficiency of 41%."}
{"id": "PMID:17466", "title": "Isolation and characterization of a neuroblastoma cell line from peripheral blood in a patient with disseminated disease.", "content": "Circulation in the blood stream of neuroblastoma cells was confirmed by establishment of a cell line from the peripheral blood of a child with disseminated disease. The morphologic, enzymatic, and chromosomal pattern of this cell line was similar to a cell line established from the primary tumor on a previous occasion. The peripheral blood smear did not demonstrate tumor cells but increased numbers of atypical monocytes; lymphoblasts were evident, which may have been unrecognized neuroblasts.", "contents": "Isolation and characterization of a neuroblastoma cell line from peripheral blood in a patient with disseminated disease. Circulation in the blood stream of neuroblastoma cells was confirmed by establishment of a cell line from the peripheral blood of a child with disseminated disease. The morphologic, enzymatic, and chromosomal pattern of this cell line was similar to a cell line established from the primary tumor on a previous occasion. The peripheral blood smear did not demonstrate tumor cells but increased numbers of atypical monocytes; lymphoblasts were evident, which may have been unrecognized neuroblasts."}
{"id": "PMID:17468", "title": "Subcellular compartmentation of creatine kinase isoenzymes in guinea pig heart.", "content": "In an attempt to determine whether a subcellular compartmentation of creatine kinase exists and if so, whether there is a different distribution of the 3 isoenzymes of CK in the cell, studies were carried out with the guinea pig heart which had been subfractionated by either isopycnic density gradient centrifugation or differential pelleting. Isoenzyme analysis of CK in the isolated subcellular fractions by electrophoresis on agarose gels, revealed that the MM isoenzyme occurred in the cytosol, myofibrils, and the microsomes while the MB isoenzyme (which is cardio-specific) was only found in the cytosol. Trace amounts of the BB isoenzyme were detected in the cytosol. Considerable CK activity was associated with the mitochondria, this did not represent the MM, the MB, or the BB isoenzymes but was a distinct and additional mitochondrial-specific form of CK. PH optima and kinetic studies were carried out to characterise and distinguish the mitochondrial isoenzyme from other CK isoenzyme activity. The evidence for a differential compartmentation of MM, MB, BB, and mitochondrial CK is discussed in relation to their possible cellular roles.", "contents": "Subcellular compartmentation of creatine kinase isoenzymes in guinea pig heart. In an attempt to determine whether a subcellular compartmentation of creatine kinase exists and if so, whether there is a different distribution of the 3 isoenzymes of CK in the cell, studies were carried out with the guinea pig heart which had been subfractionated by either isopycnic density gradient centrifugation or differential pelleting. Isoenzyme analysis of CK in the isolated subcellular fractions by electrophoresis on agarose gels, revealed that the MM isoenzyme occurred in the cytosol, myofibrils, and the microsomes while the MB isoenzyme (which is cardio-specific) was only found in the cytosol. Trace amounts of the BB isoenzyme were detected in the cytosol. Considerable CK activity was associated with the mitochondria, this did not represent the MM, the MB, or the BB isoenzymes but was a distinct and additional mitochondrial-specific form of CK. PH optima and kinetic studies were carried out to characterise and distinguish the mitochondrial isoenzyme from other CK isoenzyme activity. The evidence for a differential compartmentation of MM, MB, BB, and mitochondrial CK is discussed in relation to their possible cellular roles."}
{"id": "PMID:17467", "title": "Some new approaches to potential test systems for drugs against prostatic cancer.", "content": "We have previously reported on test systems, based on 5alpha-reductase (5alpha-RA) and arginase activities and steroid deposition in animal prostates, potentially useful in screening drugs possibly effective in cancer of the prostate. Recently, we have concentrated on the development of other in vivo and in vitro systems which may prove of further value in testing such drugs. These systems include the following: (a) The effects of drugs on 5alpha-RA activity in human and animal non-malignant and human cancerous prostatic tissues in organ culture. The parameters necessary for the maintenance of optimal 5alpha-RA in such explants have been determined, and it has been shown that certain agents (estramustine phosphate, progesterone, estradiol-17beta) can inhibit 5alpha-RA under in vitro conditions, pointing to the potential use of such an approach in screening various cytostatic agents. In addition, 65Zn deposition, the histology, and the androgen metabolism in such tissues in organ culture are being determined as additional parameters. (b) The deposition of 65Zn in the rat dorsolateral gland, particularly as affected by prolactin and testosterone, and the effects of chemotherapeutic agents on such deposition. Methotrexate and CCNU have been shown to be potent inhibitors of 65Zn deposition in the dorsolateral gland. The parameters related to zinc metabolism in the prostate are being further investigated. (c) The demonstration of receptors for estrogens (estradiol-17beta, diethylstilbestrol) in the prostate of the baboon. The various parameters related to the specificity of such receptors have been established. The development and standardization of these approaches, some facets of which are reported in the present publication, may prove them to be more sensitive, specific, and optimal than other systems and should afford an opportunity to test various combinations of drugs potentially useful in cancer of the prostate with relative speed, efficacy, and ease of manipulation.", "contents": "Some new approaches to potential test systems for drugs against prostatic cancer. We have previously reported on test systems, based on 5alpha-reductase (5alpha-RA) and arginase activities and steroid deposition in animal prostates, potentially useful in screening drugs possibly effective in cancer of the prostate. Recently, we have concentrated on the development of other in vivo and in vitro systems which may prove of further value in testing such drugs. These systems include the following: (a) The effects of drugs on 5alpha-RA activity in human and animal non-malignant and human cancerous prostatic tissues in organ culture. The parameters necessary for the maintenance of optimal 5alpha-RA in such explants have been determined, and it has been shown that certain agents (estramustine phosphate, progesterone, estradiol-17beta) can inhibit 5alpha-RA under in vitro conditions, pointing to the potential use of such an approach in screening various cytostatic agents. In addition, 65Zn deposition, the histology, and the androgen metabolism in such tissues in organ culture are being determined as additional parameters. (b) The deposition of 65Zn in the rat dorsolateral gland, particularly as affected by prolactin and testosterone, and the effects of chemotherapeutic agents on such deposition. Methotrexate and CCNU have been shown to be potent inhibitors of 65Zn deposition in the dorsolateral gland. The parameters related to zinc metabolism in the prostate are being further investigated. (c) The demonstration of receptors for estrogens (estradiol-17beta, diethylstilbestrol) in the prostate of the baboon. The various parameters related to the specificity of such receptors have been established. The development and standardization of these approaches, some facets of which are reported in the present publication, may prove them to be more sensitive, specific, and optimal than other systems and should afford an opportunity to test various combinations of drugs potentially useful in cancer of the prostate with relative speed, efficacy, and ease of manipulation."}
{"id": "PMID:17474", "title": "Aurinetricarboxylic acid: a potent inhibitor of glucose-6-phosphate dehydrogenase.", "content": "Inhibition by aurinetricarboxylic acid (ATA) of glucose-6-phosphate (G6P) dehydrogenase was \"competitive\" with respect to G6P and \"mixed type\" with respect to NADP+. Inhibited enzyme bound two molecules of ATA. Kinetic constants, Km, Ki at varying pH suggested possible binding of the inhibitor by the sulfhydryl of the enzyme; of the several enzymes tested only milk xanthine oxidase and G6P dehydrogenase from bovine adrenal was inhibited by ATA.", "contents": "Aurinetricarboxylic acid: a potent inhibitor of glucose-6-phosphate dehydrogenase. Inhibition by aurinetricarboxylic acid (ATA) of glucose-6-phosphate (G6P) dehydrogenase was \"competitive\" with respect to G6P and \"mixed type\" with respect to NADP+. Inhibited enzyme bound two molecules of ATA. Kinetic constants, Km, Ki at varying pH suggested possible binding of the inhibitor by the sulfhydryl of the enzyme; of the several enzymes tested only milk xanthine oxidase and G6P dehydrogenase from bovine adrenal was inhibited by ATA."}
{"id": "PMID:17477", "title": "[The effect of toxin II isolated from sea anemones (Anemonia sulcata) on the isolated guinea pig ileum].", "content": "When the guinea-pig isolated ileum is treated with the Toxin II from Anemonia sulcata, it releases not only acetylcholine but also serotonin. These transmitters are both involved in the spasmogenic action of the toxin.", "contents": "[The effect of toxin II isolated from sea anemones (Anemonia sulcata) on the isolated guinea pig ileum]. When the guinea-pig isolated ileum is treated with the Toxin II from Anemonia sulcata, it releases not only acetylcholine but also serotonin. These transmitters are both involved in the spasmogenic action of the toxin."}
{"id": "PMID:17478", "title": "[Demonstration of N-acetylgalactosaminyltransferase activity in the murine lymphoma YC8].", "content": "The N-acetyl-galactosaminyltransferase activity has been studied in the biological fluids of YC8-lymphoma bearing Balb/c mice. It is enhanced during tumor development from 1 to 30 times in peritoneal fluids and from 1 to 10 times in sera. This activity is nil in urines. Optimal requirements for activity have been determined. Results suggest the existence, during tumor process not only of an enhancement of enzymatic activity, but also of a new molecule synthesis, molecules which are endogenous acceptors for the enzyme.", "contents": "[Demonstration of N-acetylgalactosaminyltransferase activity in the murine lymphoma YC8]. The N-acetyl-galactosaminyltransferase activity has been studied in the biological fluids of YC8-lymphoma bearing Balb/c mice. It is enhanced during tumor development from 1 to 30 times in peritoneal fluids and from 1 to 10 times in sera. This activity is nil in urines. Optimal requirements for activity have been determined. Results suggest the existence, during tumor process not only of an enhancement of enzymatic activity, but also of a new molecule synthesis, molecules which are endogenous acceptors for the enzyme."}
{"id": "PMID:17480", "title": "Continuous-flow determination of dialyzable calcium in serum.", "content": "We describe a procedure for measuring dialyzable calcium in 60 sera per hour with use of AutoAnalyzer (Technicon) modules. The serum is buffered, then dialyzed in a regular 6-inch (15-cm) dialysis block. A constant proportion of the dialyzable calcium is fluorometrically measured. Analysis of samples containing protein, prepared by an equilibrium dialysis technique, shows that protein-bound calcium is not detected. The method requires less than 0.4 ml of serum, and is accurate, precise, and durable. No unusual care or special techniques are required during sample collection or analysis.", "contents": "Continuous-flow determination of dialyzable calcium in serum. We describe a procedure for measuring dialyzable calcium in 60 sera per hour with use of AutoAnalyzer (Technicon) modules. The serum is buffered, then dialyzed in a regular 6-inch (15-cm) dialysis block. A constant proportion of the dialyzable calcium is fluorometrically measured. Analysis of samples containing protein, prepared by an equilibrium dialysis technique, shows that protein-bound calcium is not detected. The method requires less than 0.4 ml of serum, and is accurate, precise, and durable. No unusual care or special techniques are required during sample collection or analysis."}
{"id": "PMID:17481", "title": "Continuous-flow determination of serum inorganic phosphate with a single reagent--the vanadomolybdate method re-evaluated.", "content": "The merits of the vanadomolybdate method in the determination of inorganic phosphate are highly underestimated with regard to the simplicity of the method and the stability of both the reagents and the color that is formed. The absorption curve of the phosphovanadomolybdate complex, with its maximum at 335 nm, extends into the visible range of the spectrum. This permits measurements with inexpensive tungsten-lamp colorimeters. On-stream dialysis is best done in a nitric acid medium, 0.15 mol/liter. Paralleled by the change in the H2PO4-/H3PO4 ratio, appreciable protein binding and poor dialysis efficiency are seen at lower acid concentrations (pH greater than 1.0). Optimum reaction-mixture concentrations of vanadium and molybdenum appeared to be respectively 0.2 and 5 mmol/liter up to 3 mmol of phosphate per liter, in a final acid medium of 0.2 mol/liter, concentrations considerably lower than those used in some studies published earlier. Color development with the stable combined reagent is complete after only 20 s at room temperature and the color is stable for at least 2 h. Figures on precision and accuracy demonstrate the reliability of the method.", "contents": "Continuous-flow determination of serum inorganic phosphate with a single reagent--the vanadomolybdate method re-evaluated. The merits of the vanadomolybdate method in the determination of inorganic phosphate are highly underestimated with regard to the simplicity of the method and the stability of both the reagents and the color that is formed. The absorption curve of the phosphovanadomolybdate complex, with its maximum at 335 nm, extends into the visible range of the spectrum. This permits measurements with inexpensive tungsten-lamp colorimeters. On-stream dialysis is best done in a nitric acid medium, 0.15 mol/liter. Paralleled by the change in the H2PO4-/H3PO4 ratio, appreciable protein binding and poor dialysis efficiency are seen at lower acid concentrations (pH greater than 1.0). Optimum reaction-mixture concentrations of vanadium and molybdenum appeared to be respectively 0.2 and 5 mmol/liter up to 3 mmol of phosphate per liter, in a final acid medium of 0.2 mol/liter, concentrations considerably lower than those used in some studies published earlier. Color development with the stable combined reagent is complete after only 20 s at room temperature and the color is stable for at least 2 h. Figures on precision and accuracy demonstrate the reliability of the method."}
{"id": "PMID:17482", "title": "Simultaneous measurement of phenobarbital, phenytoin, primidone, ethosuximide, and carbamazepine in serum by high-pressure liquid chromatography.", "content": "We present a method for simultaneously determining five anticonvulsants [phenobarbital, phenytoin (diphenylhydantoin), primidone, ethosuximide, and carbamazepine] in as little as 25 microliters of serum. The proteins are precipitated with an acetonitrile solution containing hexobarbital as an internal standard. The anticonvulsants are eluted from a reversed-phase column with a mobile phase consisting of an acetonitrile/phosphate buffer (19/81 by vol) at a flow rate of 3.0 ml/min. The eluted drugs are detected by their absorption at 195 nm, and quantities estimated from their peak heights. Each analysis requires about 14 min. at an optimum column temperature of 50 degrees C. The lower unit of detection for all of these drugs is less than 10 ng. Sensitivities, for serum samples, of 1.0 mg/liter for all the drugs analyzed are attained routinely. Analytical recoveries for the five drugs varied from 97 - 107%, with good day-to-day precision (CV between 3.9 and 5.9%). Of more than 30 drugs tested for possible interference, only ethotoin interferes with the analysis of phenobarbital.", "contents": "Simultaneous measurement of phenobarbital, phenytoin, primidone, ethosuximide, and carbamazepine in serum by high-pressure liquid chromatography. We present a method for simultaneously determining five anticonvulsants [phenobarbital, phenytoin (diphenylhydantoin), primidone, ethosuximide, and carbamazepine] in as little as 25 microliters of serum. The proteins are precipitated with an acetonitrile solution containing hexobarbital as an internal standard. The anticonvulsants are eluted from a reversed-phase column with a mobile phase consisting of an acetonitrile/phosphate buffer (19/81 by vol) at a flow rate of 3.0 ml/min. The eluted drugs are detected by their absorption at 195 nm, and quantities estimated from their peak heights. Each analysis requires about 14 min. at an optimum column temperature of 50 degrees C. The lower unit of detection for all of these drugs is less than 10 ng. Sensitivities, for serum samples, of 1.0 mg/liter for all the drugs analyzed are attained routinely. Analytical recoveries for the five drugs varied from 97 - 107%, with good day-to-day precision (CV between 3.9 and 5.9%). Of more than 30 drugs tested for possible interference, only ethotoin interferes with the analysis of phenobarbital."}
{"id": "PMID:17479", "title": "Children who do not talk at school.", "content": "This paper contains two case reports illustrating the use of behaviour modification in the treatment of elective mutism. The programme was carried out by two social workers in the natural environment of the home and school.", "contents": "Children who do not talk at school. This paper contains two case reports illustrating the use of behaviour modification in the treatment of elective mutism. The programme was carried out by two social workers in the natural environment of the home and school."}
{"id": "PMID:17485", "title": "Recent developments in the clinical assessment of the metabolism of aromatics by high-performance, reversed-phase chromatography with amperometric detection.", "content": "High-performance liquid chromatography with electrochemical detection has developed into a tool with excellent capability to monitor picomole amounts of individual metabolites in both tissue and body-fluid specimens. Significant technical advances in the area of microparticle chemically-bonded stationary phases have led to dramatic improvements in both sensitivity and resolution. Reversed-phase systems can be modified to include charged exchange sites by addition of detergents to the mobile phase. Adjustment of the surface charge in this manner permits capacity factors for ionic sample components to be increased or decreased. This concept is quite compatible with electrochemical detection and has provided the foundation for several clinical assays now in routine use. Examples of additional applications are presented for the determination of catecholamines in tissue, 3-methoxy-4-hydroxyphenylglycol in urine, and dopamine-beta-hydroxylase activity in human serum.", "contents": "Recent developments in the clinical assessment of the metabolism of aromatics by high-performance, reversed-phase chromatography with amperometric detection. High-performance liquid chromatography with electrochemical detection has developed into a tool with excellent capability to monitor picomole amounts of individual metabolites in both tissue and body-fluid specimens. Significant technical advances in the area of microparticle chemically-bonded stationary phases have led to dramatic improvements in both sensitivity and resolution. Reversed-phase systems can be modified to include charged exchange sites by addition of detergents to the mobile phase. Adjustment of the surface charge in this manner permits capacity factors for ionic sample components to be increased or decreased. This concept is quite compatible with electrochemical detection and has provided the foundation for several clinical assays now in routine use. Examples of additional applications are presented for the determination of catecholamines in tissue, 3-methoxy-4-hydroxyphenylglycol in urine, and dopamine-beta-hydroxylase activity in human serum."}
{"id": "PMID:17486", "title": "Flow cytometric measurement of peptidases with use of 5-nitrosalicylaldehyde and 4-methoxy-beta-naphthylamine derivatives.", "content": "Enzyme activity can be measured in single cells or in cell suspensions by either static or flow microfluorometry when a fluorogenic substrate is used. We have used amino acid derivatives of arylamines as fluorogenic substrates for tagging cellular proteinases. The liberated aromatic amine, which can diffuse from the cell, is trapped as a fluorescent insoluble Schiff-base product with 5-nitrosalicylaldehyde, with the peak of fluorescence emission shifted from lambdaem 425 nm to lambdaem 530 and 595 nm. Although the reaction is faster at pH 4 than at higher pH's, the equilibrium during the assay of certain peptidase activities is such that the liberated aromatic amine is trapped in the cell at pH values as high as 7.5. 5-Nitrosalicylaldehyde causes almost no inhibition of substrate hydrolysis at 1 mmol/liter, a concentration exceeding that required for complete trapping of reaction product. The kinetics of enzymatic reactions with four synthetic substrates are demonstrated in intact Balb 3T3 cells and sonicated preparations in the presence of 5-nitrosalicylaldehyde. Hydrolytic rates for the substrate, CBZ-ala-arg-arg-4-methoxy-beta-naphthylamine, are given for single 3T3 cells by microfluorophotometry and for suspensions of 3T3 cells by flow cytometry. The clinical value of the method is demonstrated for differentiating mixed populations of leukocytes.", "contents": "Flow cytometric measurement of peptidases with use of 5-nitrosalicylaldehyde and 4-methoxy-beta-naphthylamine derivatives. Enzyme activity can be measured in single cells or in cell suspensions by either static or flow microfluorometry when a fluorogenic substrate is used. We have used amino acid derivatives of arylamines as fluorogenic substrates for tagging cellular proteinases. The liberated aromatic amine, which can diffuse from the cell, is trapped as a fluorescent insoluble Schiff-base product with 5-nitrosalicylaldehyde, with the peak of fluorescence emission shifted from lambdaem 425 nm to lambdaem 530 and 595 nm. Although the reaction is faster at pH 4 than at higher pH's, the equilibrium during the assay of certain peptidase activities is such that the liberated aromatic amine is trapped in the cell at pH values as high as 7.5. 5-Nitrosalicylaldehyde causes almost no inhibition of substrate hydrolysis at 1 mmol/liter, a concentration exceeding that required for complete trapping of reaction product. The kinetics of enzymatic reactions with four synthetic substrates are demonstrated in intact Balb 3T3 cells and sonicated preparations in the presence of 5-nitrosalicylaldehyde. Hydrolytic rates for the substrate, CBZ-ala-arg-arg-4-methoxy-beta-naphthylamine, are given for single 3T3 cells by microfluorophotometry and for suspensions of 3T3 cells by flow cytometry. The clinical value of the method is demonstrated for differentiating mixed populations of leukocytes."}
{"id": "PMID:17488", "title": "Inorganic phosphorus in human bile.", "content": "The inorganic phosphorus concentration has been measured in fresh bile from patients undergoing cholecystectomy, usually because of cholelithiasis. The amount in common duct bile for patients with cholesterol on the stone surface was significantly higher than that for patients with some calcium carbonate in this area. For all patients with functioning gallbladders, inorganic phosphorus in gallbladder bile was always higher than that in the corresponding common duct bile. In bile from functioning gallbladders, inorganic phosphorus was linearly related to pH for cholesterol stone-formers, but values for calcium carbonate stone-formers were below the regression line and not related to pH. The results show that bile from calcium carbonate stone-formers is more dilute with respect to inorganic phosphorus.", "contents": "Inorganic phosphorus in human bile. The inorganic phosphorus concentration has been measured in fresh bile from patients undergoing cholecystectomy, usually because of cholelithiasis. The amount in common duct bile for patients with cholesterol on the stone surface was significantly higher than that for patients with some calcium carbonate in this area. For all patients with functioning gallbladders, inorganic phosphorus in gallbladder bile was always higher than that in the corresponding common duct bile. In bile from functioning gallbladders, inorganic phosphorus was linearly related to pH for cholesterol stone-formers, but values for calcium carbonate stone-formers were below the regression line and not related to pH. The results show that bile from calcium carbonate stone-formers is more dilute with respect to inorganic phosphorus."}
{"id": "PMID:17489", "title": "A practical chromogenic procedure for the diagnosis of Krabbe's disease.", "content": "Krabbe's disease is caused by a deficiency of galactocerebrosidase in organs and tissues. Determinations of galactocerebrosidase activity had required the use of galactocerebroside labeled with radiocarbon or radiohydrogen. These materials are expensive and their use is restricted to laboratories with radioactive counting facilities. An analogue of galactocerebroside, 2-hexadecanoylamino-4-nitrophenyl-beta-D-galactopyranoside, was synthesized. The hydrolysis of this analogue by extracts of tissues and cells from patients with Krabbe's disease is greatly reduced from normal levels. Cultured skin fibroblasts preparations derived from heterozygous carriers of Krabbe's disease have an intermediate level of hydrolytic activity. Thus, the analogue is a reliable chromogenic reagent for the diagnosis of patients with Krabbe's disease and for the detection of heterozygous carriers of the Krabbe trait.", "contents": "A practical chromogenic procedure for the diagnosis of Krabbe's disease. Krabbe's disease is caused by a deficiency of galactocerebrosidase in organs and tissues. Determinations of galactocerebrosidase activity had required the use of galactocerebroside labeled with radiocarbon or radiohydrogen. These materials are expensive and their use is restricted to laboratories with radioactive counting facilities. An analogue of galactocerebroside, 2-hexadecanoylamino-4-nitrophenyl-beta-D-galactopyranoside, was synthesized. The hydrolysis of this analogue by extracts of tissues and cells from patients with Krabbe's disease is greatly reduced from normal levels. Cultured skin fibroblasts preparations derived from heterozygous carriers of Krabbe's disease have an intermediate level of hydrolytic activity. Thus, the analogue is a reliable chromogenic reagent for the diagnosis of patients with Krabbe's disease and for the detection of heterozygous carriers of the Krabbe trait."}
{"id": "PMID:17490", "title": "Urinary alpha-glucosidase analysis for the detection of the adult form of Pompe's disease.", "content": "Two alpha-glucosidases from human heart, liver, muscle, kidney and urine have been separated by means of Sephadex G-100 gel filtration. The first peak (Peak I) was neutral alpha-glucosidase and the second peak (Peak II) was lysosomal acid alpha-glucosidase. Peak II was absent in a patient with the adult form of Pompe's disease. KCl stimulated the activity of the Peak II enzyme but it strongly inhibited the activity of the Peak I enzyme measured at pH 4.0. Decreases in the urinary alpha-glucosidase activity measured at pH 4.0 with added KCl and the ratio of the activity at pH 4.0 with added KCl/the activity at pH 6.5 without KCl may aid in the detection of homozygotes or heterozygotes with the adult form of Pompe's disease.", "contents": "Urinary alpha-glucosidase analysis for the detection of the adult form of Pompe's disease. Two alpha-glucosidases from human heart, liver, muscle, kidney and urine have been separated by means of Sephadex G-100 gel filtration. The first peak (Peak I) was neutral alpha-glucosidase and the second peak (Peak II) was lysosomal acid alpha-glucosidase. Peak II was absent in a patient with the adult form of Pompe's disease. KCl stimulated the activity of the Peak II enzyme but it strongly inhibited the activity of the Peak I enzyme measured at pH 4.0. Decreases in the urinary alpha-glucosidase activity measured at pH 4.0 with added KCl and the ratio of the activity at pH 4.0 with added KCl/the activity at pH 6.5 without KCl may aid in the detection of homozygotes or heterozygotes with the adult form of Pompe's disease."}
{"id": "PMID:17491", "title": "Serum gamma-glutamyl transferase activity in chronic renal failure during regular hemodialysis and after successful renal transplantation.", "content": "Serum gamma-glutamyl transferase activity (gamma-GT) was measured in 108 uraemic patients, 110 patients on regular haemodialysis and 71 sucessfully transplanted patients. The incidence of abnormal results was 11, 14 and 28%, respectively. The results in the non-dialyzed and dialyzed patients indicate that in uraemia serum gamma-GT activity remains normal and as such, significant hepatic microsomal enzyme induction does not appear to occur. Raised serum gamma-GT in uraemic patients and after renal transplantation should suggest concurrent, added, pathology such as hepatobiliary disease or the administration of hepatic microsomal enzyme inducing drugs.", "contents": "Serum gamma-glutamyl transferase activity in chronic renal failure during regular hemodialysis and after successful renal transplantation. Serum gamma-glutamyl transferase activity (gamma-GT) was measured in 108 uraemic patients, 110 patients on regular haemodialysis and 71 sucessfully transplanted patients. The incidence of abnormal results was 11, 14 and 28%, respectively. The results in the non-dialyzed and dialyzed patients indicate that in uraemia serum gamma-GT activity remains normal and as such, significant hepatic microsomal enzyme induction does not appear to occur. Raised serum gamma-GT in uraemic patients and after renal transplantation should suggest concurrent, added, pathology such as hepatobiliary disease or the administration of hepatic microsomal enzyme inducing drugs."}
{"id": "PMID:17493", "title": "Interaction of calcium ions with serum albumin in chronic renal failure.", "content": "In order to study the effect of the uremic environment on serum calcium-albumin interaction, ten adult subjects with chronic renal failure (creatinine clearances below 20 ml/min) and five adult normal subjects, had their serum ionic calcium (Orion SS-20) determined at three different serum pH values. At similar serum protein levels, the correlations between serum ionic calcium pH were: (a) normals: number of pairs = 15, r = -0.90, p less than 0.01, Ca2+ = 4.54-0.484 pH. (b) uremics: number of pairs=15, r=-0.97, p less than 0.01, Ca2+=4.02-0.429 pH. These regressions were similar as far as the slopes (Fslope=0.62, p greater than 0.05) but had different intercepts (Fintercepts=64.34, p less than 0.01). These results confirm that uremics, when compared to normal subjects, present an ionic hypocalcemia at any level of serum pH. They also show that serum calcium-albumin interaction is normal in uremia. In view of the above results, it can be suggested that, among several possible causes, alterations in the binding-affinity of calcium ions to serum albumin can be excluded as an additional factor of secondary hyperparathyroidism in uremia.", "contents": "Interaction of calcium ions with serum albumin in chronic renal failure. In order to study the effect of the uremic environment on serum calcium-albumin interaction, ten adult subjects with chronic renal failure (creatinine clearances below 20 ml/min) and five adult normal subjects, had their serum ionic calcium (Orion SS-20) determined at three different serum pH values. At similar serum protein levels, the correlations between serum ionic calcium pH were: (a) normals: number of pairs = 15, r = -0.90, p less than 0.01, Ca2+ = 4.54-0.484 pH. (b) uremics: number of pairs=15, r=-0.97, p less than 0.01, Ca2+=4.02-0.429 pH. These regressions were similar as far as the slopes (Fslope=0.62, p greater than 0.05) but had different intercepts (Fintercepts=64.34, p less than 0.01). These results confirm that uremics, when compared to normal subjects, present an ionic hypocalcemia at any level of serum pH. They also show that serum calcium-albumin interaction is normal in uremia. In view of the above results, it can be suggested that, among several possible causes, alterations in the binding-affinity of calcium ions to serum albumin can be excluded as an additional factor of secondary hyperparathyroidism in uremia."}
{"id": "PMID:17494", "title": "A micro-radiochemical assay for alpha-1,4-glucosidase and its use in the assessment of type II glycogenosis (Pompe's disease).", "content": "An assay for alpha-1,4-glucosidase (acid maltase) activity which is deficient in Pompe's disease is described. The assay can be used to measure the enzyme in cultured skin fibroblasts, cultured amniotic cells and peripheral blood leucocytes. [U-14 C]Maltose is used as the substrate in a total assay volume of 8 microliter. The product, [U-14C]glucose, is separated from the substrate by cellulose thin-layer chromatography. The procedure permits replicate assays from 400 microliter whole blood and from amniotic cells in primary culture. Discrimination of the heterozygous Pompe state appears to be facilitated.", "contents": "A micro-radiochemical assay for alpha-1,4-glucosidase and its use in the assessment of type II glycogenosis (Pompe's disease). An assay for alpha-1,4-glucosidase (acid maltase) activity which is deficient in Pompe's disease is described. The assay can be used to measure the enzyme in cultured skin fibroblasts, cultured amniotic cells and peripheral blood leucocytes. [U-14 C]Maltose is used as the substrate in a total assay volume of 8 microliter. The product, [U-14C]glucose, is separated from the substrate by cellulose thin-layer chromatography. The procedure permits replicate assays from 400 microliter whole blood and from amniotic cells in primary culture. Discrimination of the heterozygous Pompe state appears to be facilitated."}
{"id": "PMID:17495", "title": "A radioimmunoassay for the R-type binders of cobalamin.", "content": "A radioimmunoassay of R-type binders of cobalmin was devised and tested. The assay incorporated an antibody against purified human salivary R binder as the binding reagent. The labeled ligand was cyano[57Co]cobalamin bound to the R binder of pooled human saliva. The standard source of unlabeled ligand was also from human saliva of known R binder content. The assay was responsive to R binders of several sources, to either pure R or that of crude sources and equally to R binder saturated or unsaturated with cobalamin. It was not responsive to transcobalamin II. The assay was reproducible and reliable.", "contents": "A radioimmunoassay for the R-type binders of cobalamin. A radioimmunoassay of R-type binders of cobalmin was devised and tested. The assay incorporated an antibody against purified human salivary R binder as the binding reagent. The labeled ligand was cyano[57Co]cobalamin bound to the R binder of pooled human saliva. The standard source of unlabeled ligand was also from human saliva of known R binder content. The assay was responsive to R binders of several sources, to either pure R or that of crude sources and equally to R binder saturated or unsaturated with cobalamin. It was not responsive to transcobalamin II. The assay was reproducible and reliable."}
{"id": "PMID:17496", "title": "An improved method for the determination of acetylcholinesterase activity in rectal biopsy tissue from patients with Hirschsprung's disease.", "content": "A method is described for the assay of acetylcholinesterase in tissue samples using the selective cholinesterase inhibitor, lysivane (10-(alpha-diethylaminopropyl) phenothiazine hydrochloride). Significantly increased enzyme activity is found in rectal biopsy specimens from patients with Hirschsprung's disease (p less than 0.001) indicating the diagnostic usefulness of the assay.", "contents": "An improved method for the determination of acetylcholinesterase activity in rectal biopsy tissue from patients with Hirschsprung's disease. A method is described for the assay of acetylcholinesterase in tissue samples using the selective cholinesterase inhibitor, lysivane (10-(alpha-diethylaminopropyl) phenothiazine hydrochloride). Significantly increased enzyme activity is found in rectal biopsy specimens from patients with Hirschsprung's disease (p less than 0.001) indicating the diagnostic usefulness of the assay."}
{"id": "PMID:17497", "title": "Respiratory acidosis and alkalosis.", "content": "The physiology of respiratory control of acid-base balance is reviewed. The pathophysiological mechanisms during hypercapnia and hypocapnia are discussed in the light of the causes and clinical manifestations of these disturbances. In addition to the role of the kidney in the compensatory processes of these disturbances, renal functional changes during acute and chronic pulmonary acid-base derangement is discussed. Some of the difficulties encountered in the patient with chronic renal disease in whom respiratory abnormalities may be present are also discussed.", "contents": "Respiratory acidosis and alkalosis. The physiology of respiratory control of acid-base balance is reviewed. The pathophysiological mechanisms during hypercapnia and hypocapnia are discussed in the light of the causes and clinical manifestations of these disturbances. In addition to the role of the kidney in the compensatory processes of these disturbances, renal functional changes during acute and chronic pulmonary acid-base derangement is discussed. Some of the difficulties encountered in the patient with chronic renal disease in whom respiratory abnormalities may be present are also discussed."}
{"id": "PMID:17498", "title": "Metabolic acidosis and alkalosis.", "content": "The factors controlling renal bicarbonate reabsorption and acid excretion under normal conditions and in the presence of metabolic acidosis and alkalosis are reviewed. The methods used to assess distal acidification and its limitations are also discussed. Measurement of urinary pCO2 in maximally alkaline urine (pH greater than 7.8) is a very useful qualitative method to assess distal acidification. The finding of a low urinary pCO2 in maximally alkaline urine indicates a distal acidification defect. We propose that both the secretory and gradient defect types of distal renal tubular acidosis are associated with a low urinary pCO2 when the urine is maximally alkaline. Sodium sulfate and neutral phosphate infusion may allow distinction between a secretory and gradient defect. Sodium sulfate lowers urine pH in the gradient defect but fails to produce the same response in the secretory defect. Neutral phosphate infusion when urine pH (6.8-7.4) is close to the pK of phosphate (6.8) results in an increase in urinary pCO2 in the gradient defect but not in the secretory defect. The mechanisms of generation, maintenance and treatment of metabolic alkalosis are also discussed.", "contents": "Metabolic acidosis and alkalosis. The factors controlling renal bicarbonate reabsorption and acid excretion under normal conditions and in the presence of metabolic acidosis and alkalosis are reviewed. The methods used to assess distal acidification and its limitations are also discussed. Measurement of urinary pCO2 in maximally alkaline urine (pH greater than 7.8) is a very useful qualitative method to assess distal acidification. The finding of a low urinary pCO2 in maximally alkaline urine indicates a distal acidification defect. We propose that both the secretory and gradient defect types of distal renal tubular acidosis are associated with a low urinary pCO2 when the urine is maximally alkaline. Sodium sulfate and neutral phosphate infusion may allow distinction between a secretory and gradient defect. Sodium sulfate lowers urine pH in the gradient defect but fails to produce the same response in the secretory defect. Neutral phosphate infusion when urine pH (6.8-7.4) is close to the pK of phosphate (6.8) results in an increase in urinary pCO2 in the gradient defect but not in the secretory defect. The mechanisms of generation, maintenance and treatment of metabolic alkalosis are also discussed."}
{"id": "PMID:17500", "title": "Methadone maintenance: effect of urinary pH on renal clearance in chronic high and low doses.", "content": "The subjects were 12 male patients stabilized on methadone for many months or years. A comparison was made of the plasma levels and renal clearance of methadone between patients on \"high\" doses (80 to 110 mg/day) and those on \"low\" doses (15 to 40 mg/day). A general trend to higher renal clearance was seen in the \"high\" -dose group, but on more detailed examination there was a direct correlation only when the patients were categorized by urinary pH. At low pHs, there was nearly a 3-fold increase in renal clearance which was associated with a decreased major metabolite to methadone ratio. No evidence for a difference in rate of metabolism between the two groups was found nor were there differences in hepatic function. It was concluded that urinary pH was a major factor in renal clearance of methadone.", "contents": "Methadone maintenance: effect of urinary pH on renal clearance in chronic high and low doses. The subjects were 12 male patients stabilized on methadone for many months or years. A comparison was made of the plasma levels and renal clearance of methadone between patients on \"high\" doses (80 to 110 mg/day) and those on \"low\" doses (15 to 40 mg/day). A general trend to higher renal clearance was seen in the \"high\" -dose group, but on more detailed examination there was a direct correlation only when the patients were categorized by urinary pH. At low pHs, there was nearly a 3-fold increase in renal clearance which was associated with a decreased major metabolite to methadone ratio. No evidence for a difference in rate of metabolism between the two groups was found nor were there differences in hepatic function. It was concluded that urinary pH was a major factor in renal clearance of methadone."}
{"id": "PMID:17501", "title": "The crystalline salts of calcium bilirubinate in human gallstones.", "content": "1. The acid, neutral and \"intermediate\" salts of calcium bilirubinate have been synthesized. 2. All are crystalline, and the intermediate salt which has 1 1/2 molecules of bilirubin per calcium atom probably has a crystal structure containing molecules of both acid and neutral salts. 3. The acid or intermediate salts have been found in 14 out of 70 gallstones analysed recently by X-ray diffraction.", "contents": "The crystalline salts of calcium bilirubinate in human gallstones. 1. The acid, neutral and \"intermediate\" salts of calcium bilirubinate have been synthesized. 2. All are crystalline, and the intermediate salt which has 1 1/2 molecules of bilirubin per calcium atom probably has a crystal structure containing molecules of both acid and neutral salts. 3. The acid or intermediate salts have been found in 14 out of 70 gallstones analysed recently by X-ray diffraction."}
{"id": "PMID:17512", "title": "Autoimmunity, oncornaviruses, and lymphomagenesis.", "content": "The interactions between aberrant immune responses and C-type oncornaviruses in mice are complex. These viruses may be activated during certain immune responses, e.g., histocompatibility reactions, in the face of chronic immunosuppression. Oncornaviruses, themselves, may induce autoaggressive cell-mediated responses in certain lymphoid subpopulations, and these autoimmune reactions may be important in subsequent lymphomagenesis. Parallel events may occur in other animal models, e.g., the NZB mouse, and in certain human disorders, e.g., Sj\u00f6gren's syndrome, systemic lupus erythematosus, and myasthenia gravis.", "contents": "Autoimmunity, oncornaviruses, and lymphomagenesis. The interactions between aberrant immune responses and C-type oncornaviruses in mice are complex. These viruses may be activated during certain immune responses, e.g., histocompatibility reactions, in the face of chronic immunosuppression. Oncornaviruses, themselves, may induce autoaggressive cell-mediated responses in certain lymphoid subpopulations, and these autoimmune reactions may be important in subsequent lymphomagenesis. Parallel events may occur in other animal models, e.g., the NZB mouse, and in certain human disorders, e.g., Sj\u00f6gren's syndrome, systemic lupus erythematosus, and myasthenia gravis."}
{"id": "PMID:17513", "title": "Predictability of arterial pH and PCO2 from right atrial blood samples in experimental animal.", "content": "Arterial and right atrial blood samples were drawn simultaneously under acutely changing acid-base and ventilatory conditions in a series of experiments carried out in nine pigs. The pH, PCO2, bicarbonate concentration and base excess from arterial and right atrial blood are compared. The predictability of the arterial values from the right atrial values is discussed. It is concluded that right atrial blood samples are approximately as informative as arterial blood samples for determining the acid-base status under both normal and acutely changed acid-base and ventilatory conditions.", "contents": "Predictability of arterial pH and PCO2 from right atrial blood samples in experimental animal. Arterial and right atrial blood samples were drawn simultaneously under acutely changing acid-base and ventilatory conditions in a series of experiments carried out in nine pigs. The pH, PCO2, bicarbonate concentration and base excess from arterial and right atrial blood are compared. The predictability of the arterial values from the right atrial values is discussed. It is concluded that right atrial blood samples are approximately as informative as arterial blood samples for determining the acid-base status under both normal and acutely changed acid-base and ventilatory conditions."}
{"id": "PMID:17516", "title": "Fiberoptic bronchoscopy and culture bacteria from the lower respiratory.", "content": "Forty-five specimens were obtained by sequential translaryngeal aspiration and fiberoptic bronchoscopy from 31 clinically unifected patients with lung cancer in order to evaluate the reliability of routine fiberoptic bronchoscopy for culture of the lower respiratory tract. Bacteria were recovered brom 98 percent (44) of the specimens obtained via fiberoptic bronchoscopy and from 58 percent (26) of the specimens obtained by the preceding translaryngeal aspiration. The microorganisms grown from cultures of specimens obtained by fiberoptic bronchoscopy consisted of mixtures of both nonpathogenic and potenitally pathogenic bacteria. Potentially pathogenic bacteria were present in 87 percent (39) of the specimens from fiberoptic bronchoscopy and 31 percent (14) of specimens from translayngeal aspiration. The results of cultures from the two procedures agreed completely in only a single instance. Culture of washings or secretions obtained by routine fiberoptic bronchoscopy is not recommended because it provides inaccurate and clinically confusing information about the presence or types of bacteria in the lower respiratory tract prior to instrumentation.", "contents": "Fiberoptic bronchoscopy and culture bacteria from the lower respiratory. Forty-five specimens were obtained by sequential translaryngeal aspiration and fiberoptic bronchoscopy from 31 clinically unifected patients with lung cancer in order to evaluate the reliability of routine fiberoptic bronchoscopy for culture of the lower respiratory tract. Bacteria were recovered brom 98 percent (44) of the specimens obtained via fiberoptic bronchoscopy and from 58 percent (26) of the specimens obtained by the preceding translaryngeal aspiration. The microorganisms grown from cultures of specimens obtained by fiberoptic bronchoscopy consisted of mixtures of both nonpathogenic and potenitally pathogenic bacteria. Potentially pathogenic bacteria were present in 87 percent (39) of the specimens from fiberoptic bronchoscopy and 31 percent (14) of specimens from translayngeal aspiration. The results of cultures from the two procedures agreed completely in only a single instance. Culture of washings or secretions obtained by routine fiberoptic bronchoscopy is not recommended because it provides inaccurate and clinically confusing information about the presence or types of bacteria in the lower respiratory tract prior to instrumentation."}
{"id": "PMID:17517", "title": "Patterns of antipsychotic drug use in four Southeastern state hospitals.", "content": "The drug prescriptions of patients in the four mental hospitals of a state were obtained as of a specific date and subjected to various analyses. The results disclose a high frequency of antiparkinson drug orders (41.5% of the patients), their relationship to polypharmacy (30% of the antipsychotic drug prescriptions were for two or more to be administered simultaneously), the direct relationship between the antipsychotic dose level and antiparkinson drug and PRN orders and the incidence of multiple dose schedules (75%). Also other prescription practices which have received little or no attention are described and discussed.", "contents": "Patterns of antipsychotic drug use in four Southeastern state hospitals. The drug prescriptions of patients in the four mental hospitals of a state were obtained as of a specific date and subjected to various analyses. The results disclose a high frequency of antiparkinson drug orders (41.5% of the patients), their relationship to polypharmacy (30% of the antipsychotic drug prescriptions were for two or more to be administered simultaneously), the direct relationship between the antipsychotic dose level and antiparkinson drug and PRN orders and the incidence of multiple dose schedules (75%). Also other prescription practices which have received little or no attention are described and discussed."}
{"id": "PMID:17514", "title": "The ventilatory response in uncomplicated diabetic ketoacidosis.", "content": "The ventilatory response to uncomplicated sub-acute metabolic acidosis was studied by measuring arterial blood CO2 tension (PaCO2) and pH in 27 episodes of diabetic ketoacidosis without coexisting lactic acidosis. From those data, regression equations and 95% confidence bands were calculated for the relations between PaCO2 and pH. These relations were very similar to those previously described by others in patients with chronic uremic acidosis.", "contents": "The ventilatory response in uncomplicated diabetic ketoacidosis. The ventilatory response to uncomplicated sub-acute metabolic acidosis was studied by measuring arterial blood CO2 tension (PaCO2) and pH in 27 episodes of diabetic ketoacidosis without coexisting lactic acidosis. From those data, regression equations and 95% confidence bands were calculated for the relations between PaCO2 and pH. These relations were very similar to those previously described by others in patients with chronic uremic acidosis."}
{"id": "PMID:17520", "title": "Isolation and identification of the major metabolite of albuterol in human urine.", "content": "The major urinary metabolite of albuterol in man was isolated and purified by ion-exchange chromatography and countercurrent distribution. On the basis of proton magnetic resonance, infrared, and mass-spectral analysis, enzymic hydrolysis, and assay of inorganic sulfate after acid hydrolysis, the metabolite has been identified as the 4'-O-sulfate ester of albuterol.", "contents": "Isolation and identification of the major metabolite of albuterol in human urine. The major urinary metabolite of albuterol in man was isolated and purified by ion-exchange chromatography and countercurrent distribution. On the basis of proton magnetic resonance, infrared, and mass-spectral analysis, enzymic hydrolysis, and assay of inorganic sulfate after acid hydrolysis, the metabolite has been identified as the 4'-O-sulfate ester of albuterol."}
{"id": "PMID:17523", "title": "Pharmacokinetics of intravenously injected chloramphenicol in baby pigs.", "content": "A sensitive fluorometric assay procedure for chloramphenicol and its metabolites was used to measure distribution in tissues and elimination of the drug after injection of 22 mg/kg iv in baby pigs. Disappearance of chloramphenicol from plasma was biphasic; an initial component was rapid (half-life about 9 min) and a second component had a half-life of 55 min. The total chloramphenicol levels in tissues and body fluids had half-life periods of 1-1.5 hr and dropped below limits of detectability within 9 hr after injection. About 80% of the injected dose was recovered from urine collected over the first 6 hr, and none thereafter. Fecal elimination, if occurring, was negligible.", "contents": "Pharmacokinetics of intravenously injected chloramphenicol in baby pigs. A sensitive fluorometric assay procedure for chloramphenicol and its metabolites was used to measure distribution in tissues and elimination of the drug after injection of 22 mg/kg iv in baby pigs. Disappearance of chloramphenicol from plasma was biphasic; an initial component was rapid (half-life about 9 min) and a second component had a half-life of 55 min. The total chloramphenicol levels in tissues and body fluids had half-life periods of 1-1.5 hr and dropped below limits of detectability within 9 hr after injection. About 80% of the injected dose was recovered from urine collected over the first 6 hr, and none thereafter. Fecal elimination, if occurring, was negligible."}
{"id": "PMID:17524", "title": "Biotransformation of cannabidiol in mice. Identification of new acid metabolites.", "content": "The in vivo metabolism of cannabidiol (CBD) was investigated in mice. Following the ip administration of CBD to mice, livers were removed and metabolites were extracted with ethyl acetate prior to partial purification on Sephadex LH-20 columns. Fractions from the columns were converted into trimethylsilyl, d9-trimethylsilyl, and methylester-trimethylsilyl derivatives for analysis by gas-liquid chromatography-mass spectrometry. In addition, metabolites containing carboxylic acid and ketone functional groups were reduced to alcohols with lithium aluminum deuteride before trimethylsilation. A total of 22 metabolites were characterized, 14 of which had not been reported previously. The metabolites could be categorized as follows: monohydroxylated (N=2), dihydroxylated (N=3), CBD-7-oic acid, side chain hydroxy-GBD-7-oic acids (N=3), side-chain acids (N=3), 7-hydroxy-side-chain acids (N=4), 6-oxo-side-chain acids (N=3) and glucuronide conjugates (N=3). The most significant biotransformations were glucuronide conjugation and, to a lesser extent, formation of CBD-7-oic acid.", "contents": "Biotransformation of cannabidiol in mice. Identification of new acid metabolites. The in vivo metabolism of cannabidiol (CBD) was investigated in mice. Following the ip administration of CBD to mice, livers were removed and metabolites were extracted with ethyl acetate prior to partial purification on Sephadex LH-20 columns. Fractions from the columns were converted into trimethylsilyl, d9-trimethylsilyl, and methylester-trimethylsilyl derivatives for analysis by gas-liquid chromatography-mass spectrometry. In addition, metabolites containing carboxylic acid and ketone functional groups were reduced to alcohols with lithium aluminum deuteride before trimethylsilation. A total of 22 metabolites were characterized, 14 of which had not been reported previously. The metabolites could be categorized as follows: monohydroxylated (N=2), dihydroxylated (N=3), CBD-7-oic acid, side chain hydroxy-GBD-7-oic acids (N=3), side-chain acids (N=3), 7-hydroxy-side-chain acids (N=4), 6-oxo-side-chain acids (N=3) and glucuronide conjugates (N=3). The most significant biotransformations were glucuronide conjugation and, to a lesser extent, formation of CBD-7-oic acid."}
{"id": "PMID:17521", "title": "Absorption, excretion and disposition of cyclindole in laboratory animals and human volunteers.", "content": "Radioactivity from orally administered single doses of cyclindole-14C was excreted primarily in the urine of the rat (99%/48 hr), monkey (80%/120 hr), and dog (70%/144 hr). Approximately 38-58% of a daily dose of cyclindole was recovered from 24-hr human urine, as determined by gas chromatography. Substantial amounts of unchanged drug were voided by dogs. Cyclindole was metabolized primarily by N-demethylation and/or hydroxylation in the 7-position. Hydroxylation at the 6-carbon atom was of minor importance in humans only; none of the animal species excreted the 6-hydroxy metabolite. Dogs were capable of N-demethylation, but no metabolites oxidized at the 6- or 7-carbon atoms were detected in dog urine.", "contents": "Absorption, excretion and disposition of cyclindole in laboratory animals and human volunteers. Radioactivity from orally administered single doses of cyclindole-14C was excreted primarily in the urine of the rat (99%/48 hr), monkey (80%/120 hr), and dog (70%/144 hr). Approximately 38-58% of a daily dose of cyclindole was recovered from 24-hr human urine, as determined by gas chromatography. Substantial amounts of unchanged drug were voided by dogs. Cyclindole was metabolized primarily by N-demethylation and/or hydroxylation in the 7-position. Hydroxylation at the 6-carbon atom was of minor importance in humans only; none of the animal species excreted the 6-hydroxy metabolite. Dogs were capable of N-demethylation, but no metabolites oxidized at the 6- or 7-carbon atoms were detected in dog urine."}
{"id": "PMID:17525", "title": "The effects of delta9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat.", "content": "The effects of delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on hydroxylation of estradiol and testosterone in rat liver microsomes were investigated. Acute and chronic treatment of male and female rats with either cannabinoid, 2 or 10 mg/kg, significantly elevated steroid hydroxylase activity. Acute administration of THC or CBD, 10 mg/kg, evoked no detectable changes in cytochrome P-450 levels, but a significant decrease in those of cytochrome b5. Chronic administration of THC or CBD, 2 mg/kg, decreased levels of cytochrome P-450, whereas cytochrome b5 levels appeared normal. Acute doses of THC or CBD at 10 mg/kg significantly depressed testosterone formation in testis microsomes. Chronic THC, 2 mg/kg, but not CBD, evoked the most dramatic decrease in testicular enzyme activity.", "contents": "The effects of delta9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat. The effects of delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on hydroxylation of estradiol and testosterone in rat liver microsomes were investigated. Acute and chronic treatment of male and female rats with either cannabinoid, 2 or 10 mg/kg, significantly elevated steroid hydroxylase activity. Acute administration of THC or CBD, 10 mg/kg, evoked no detectable changes in cytochrome P-450 levels, but a significant decrease in those of cytochrome b5. Chronic administration of THC or CBD, 2 mg/kg, decreased levels of cytochrome P-450, whereas cytochrome b5 levels appeared normal. Acute doses of THC or CBD at 10 mg/kg significantly depressed testosterone formation in testis microsomes. Chronic THC, 2 mg/kg, but not CBD, evoked the most dramatic decrease in testicular enzyme activity."}
{"id": "PMID:17527", "title": "Glucuronidation and deglucuronidation reactions in hepatic and extrahepatic tissues during perinatal development.", "content": "The relative activities of uridine diphosphoglucuronyltransferase (UDPGT) and beta-glucuronidase (betaG) were measured during perinatal development of hepatic and extrahepatic tissues to determine the balance between glucuronidation and deglucuronidation reactions at different developmental stages. Liver, lung, kidney, intestine, and placenta were studied in guinea pigs and rabbits. In general, betaG activities exceeded those of UDPGT in fetal tissues, whereas the converse was evident in adults. There were significant species and age differences in the onset of betaG and UDPGT activities and the occurrence of developmental peaks. A dramatic betaG developmental peak was observed in fetal guinea pig intestine and newborn rabbit intestine. Both microsomal and lysosomal betaG exhibited similar developmental patterns in all tissues tested. Hepatic nonsteroid UDPGT activities were higher at parturition than in adult animals, whereas no such developmental peak occurred for steroid UDPGT. Triton X-100 activated fetal UDPGT in vitro by approximately the same factor as it did for adult UDPGT.", "contents": "Glucuronidation and deglucuronidation reactions in hepatic and extrahepatic tissues during perinatal development. The relative activities of uridine diphosphoglucuronyltransferase (UDPGT) and beta-glucuronidase (betaG) were measured during perinatal development of hepatic and extrahepatic tissues to determine the balance between glucuronidation and deglucuronidation reactions at different developmental stages. Liver, lung, kidney, intestine, and placenta were studied in guinea pigs and rabbits. In general, betaG activities exceeded those of UDPGT in fetal tissues, whereas the converse was evident in adults. There were significant species and age differences in the onset of betaG and UDPGT activities and the occurrence of developmental peaks. A dramatic betaG developmental peak was observed in fetal guinea pig intestine and newborn rabbit intestine. Both microsomal and lysosomal betaG exhibited similar developmental patterns in all tissues tested. Hepatic nonsteroid UDPGT activities were higher at parturition than in adult animals, whereas no such developmental peak occurred for steroid UDPGT. Triton X-100 activated fetal UDPGT in vitro by approximately the same factor as it did for adult UDPGT."}
{"id": "PMID:17529", "title": "Metabolism of 7,12-dimethylbenz[a]anthracene in mouse skin homogenates analyzed with high-pressure liquid chromatography.", "content": "The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) in epidermal homogenates from 3-methylcholanthrene-pretreated mice was analyzed with high-pressure liquid chromatography. Metabolism was undetectable in the absence of pretreatment. Specific activities in epidermal homogenates from pretreated mice were found to be approximately 100 to 1000 times lower than those observed in comparable incubations containing hepatic microsomes from MC-pretreated rats. The major metabolite formed was identified as 7-hydroxymethyl-12-methylbenz[a]anthracene. Each of the known hydroxymethyl metabolites also was present in detectable quantities. The K-region diol was not measurably present in incubations with mouse skin homogenates or rat liver microsomes from MC-pretreated animals. 7,8-Benzoflavone, 5,6-benzoflavone, and 17-beta-estradiol were found to be potent inhibitors of the metabolic transformation of DMBA by epidermal homogenates in vitro, whereas butylated hydroxytoluene and 1,1,1-trichloro-2,3-propene oxide had little effect on or enhanced metabolite formation from DMBA in vitro.", "contents": "Metabolism of 7,12-dimethylbenz[a]anthracene in mouse skin homogenates analyzed with high-pressure liquid chromatography. The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) in epidermal homogenates from 3-methylcholanthrene-pretreated mice was analyzed with high-pressure liquid chromatography. Metabolism was undetectable in the absence of pretreatment. Specific activities in epidermal homogenates from pretreated mice were found to be approximately 100 to 1000 times lower than those observed in comparable incubations containing hepatic microsomes from MC-pretreated rats. The major metabolite formed was identified as 7-hydroxymethyl-12-methylbenz[a]anthracene. Each of the known hydroxymethyl metabolites also was present in detectable quantities. The K-region diol was not measurably present in incubations with mouse skin homogenates or rat liver microsomes from MC-pretreated animals. 7,8-Benzoflavone, 5,6-benzoflavone, and 17-beta-estradiol were found to be potent inhibitors of the metabolic transformation of DMBA by epidermal homogenates in vitro, whereas butylated hydroxytoluene and 1,1,1-trichloro-2,3-propene oxide had little effect on or enhanced metabolite formation from DMBA in vitro."}
{"id": "PMID:17534", "title": "[Splenic infarcts in Goodpasture's syndrome: its significance for diagnosis, prognosis, and treatment (author's transl)].", "content": "Necrotising splenic arteritis with numerous extensive anaemic splenic infarcts was found in four cases of Goodpasture's syndrome with the necrotising variant of rapidly progressive glomerulonephritis. The disease was rapidly fatal. Early scanning of splenic infarcts for diagnostic, prognostic and therapeutic purposes of the fulminating form of Goodpasture's syndrome is recommended.", "contents": "[Splenic infarcts in Goodpasture's syndrome: its significance for diagnosis, prognosis, and treatment (author's transl)]. Necrotising splenic arteritis with numerous extensive anaemic splenic infarcts was found in four cases of Goodpasture's syndrome with the necrotising variant of rapidly progressive glomerulonephritis. The disease was rapidly fatal. Early scanning of splenic infarcts for diagnostic, prognostic and therapeutic purposes of the fulminating form of Goodpasture's syndrome is recommended."}
{"id": "PMID:17531", "title": "Microsomal N-hydroxylation of trans-4'-halo-4-acetamidostilbenes.", "content": "Hamster liver microsomes catalyze the N-hydroxylation of trans-4-acetamidostilbene and its 4'-Cl and 4'-F analogs. Other metabolites which were detected and quantitated were the 4'-OH derivative of trans-4-acetamidostilbene and the glycolamides of the 4'-Cl and 4'-F compounds. The kinetics of metabolism of the acetamidostilbenes were also determined. The apparent KM values of N-hydroxylation of the four substrates were similar, but the maximal velocities showed marked variations. The Vmax for the 4'-Br analog was 16% of that of trans-4-acetamidostilbene, and the rate of N-hydroxylation of the 4'Cl and 4'-F analogs was only 3% of that of the parent compound.", "contents": "Microsomal N-hydroxylation of trans-4'-halo-4-acetamidostilbenes. Hamster liver microsomes catalyze the N-hydroxylation of trans-4-acetamidostilbene and its 4'-Cl and 4'-F analogs. Other metabolites which were detected and quantitated were the 4'-OH derivative of trans-4-acetamidostilbene and the glycolamides of the 4'-Cl and 4'-F compounds. The kinetics of metabolism of the acetamidostilbenes were also determined. The apparent KM values of N-hydroxylation of the four substrates were similar, but the maximal velocities showed marked variations. The Vmax for the 4'-Br analog was 16% of that of trans-4-acetamidostilbene, and the rate of N-hydroxylation of the 4'Cl and 4'-F analogs was only 3% of that of the parent compound."}
{"id": "PMID:17536", "title": "[Stimulation of H+ secretion and serum gastrin by intra-operative electrical vagal stimulation before and after proximal selective vagotomy (author's transl)].", "content": "H+ secretion and gastrin concentration were measured before and after electric vagal stimulation during proximal selective vagotomy in 29 patients with duodenal ulcers. Before vagotomy, H+ secretion and serum gastrin concentration significantly rose after stimulation, while after complete vagotomy H+ secretion remained below basal values, although serum gastrin concentration was significantly increased. These results indicate that without vagal innervation there is no gastrin secretion within physiological levels. The method is suitable for testing the completeness of the vagotomy, the results not agreeing with those obtained by pressure measurements (Burge's method).", "contents": "[Stimulation of H+ secretion and serum gastrin by intra-operative electrical vagal stimulation before and after proximal selective vagotomy (author's transl)]. H+ secretion and gastrin concentration were measured before and after electric vagal stimulation during proximal selective vagotomy in 29 patients with duodenal ulcers. Before vagotomy, H+ secretion and serum gastrin concentration significantly rose after stimulation, while after complete vagotomy H+ secretion remained below basal values, although serum gastrin concentration was significantly increased. These results indicate that without vagal innervation there is no gastrin secretion within physiological levels. The method is suitable for testing the completeness of the vagotomy, the results not agreeing with those obtained by pressure measurements (Burge's method)."}
{"id": "PMID:17537", "title": "Hepatic enzymes, their induction and usefulness in predicting maximal serum bilirubin levels in premature newborn infants.", "content": "Sixty-seven babies were utilized to (a) document the serum bilirubin lowering effect and safety of a phenobarbitone and nikethamide combination in neonatal hyperbilirubinaemia of non-hemolytic origin; (b) determine whether birthweight and/or SGOT, SGPT or SGGT activity on day one of life correlated with the maximum serum bilirubin level achieved; and (c) investigate the pattern of hepatic enzyme levels in serum under normal conditions anf following drug induction. Results indicate a significantly lower serum bilirubin level in the treated group of babies. Birthweight and day one SGGT levels, and SGGT/birthweight ratio correlated well with the maximum serum bilirubin reached, the latter ratio being particularly useful in predicting the degree of hyperbilirubinaemia.", "contents": "Hepatic enzymes, their induction and usefulness in predicting maximal serum bilirubin levels in premature newborn infants. Sixty-seven babies were utilized to (a) document the serum bilirubin lowering effect and safety of a phenobarbitone and nikethamide combination in neonatal hyperbilirubinaemia of non-hemolytic origin; (b) determine whether birthweight and/or SGOT, SGPT or SGGT activity on day one of life correlated with the maximum serum bilirubin level achieved; and (c) investigate the pattern of hepatic enzyme levels in serum under normal conditions anf following drug induction. Results indicate a significantly lower serum bilirubin level in the treated group of babies. Birthweight and day one SGGT levels, and SGGT/birthweight ratio correlated well with the maximum serum bilirubin reached, the latter ratio being particularly useful in predicting the degree of hyperbilirubinaemia."}
{"id": "PMID:17538", "title": "In vitro pharmacology of the opioid peptides, enkephalins and endorphins.", "content": "In the guinea-pig ileum methionine-enkephalin, normorphine and morphine are equipotent in depressing electrically evoked contractions; leucine-enkephalin has about 25% of the activity. The mouse vas deferens is more sensitive to the enkephalins which are 30 to 60 times more potent than morphine. Fragments of beta-lipotropin61-91 (beta-endorphin) having sequences up to LPH76 are more potent in the mouse vas deferens than in the guinea-pig ileum but beta-endorphin is about equipotent in the two preparations. None of the peptides has antagonist activity. Methionine-enkephalin and normorphine are equipotent in inhibiting [3H]-naloxone binding by homogenate of guinea-pig brain in the absence of Na+ while leucine-enkephalin has only 25% of this activity. In the guinea-pig ileum, naloxone antagonises normorhine and the enkephalins equally well whereas in the mouse vas deferens about ten times more naloxone is required for the enkophalins that for normorphine. Methionine-enkephalin depresses output of acetylcholine in the guinea-pig ileum and of noradrenaline in the mouse vas deferens.", "contents": "In vitro pharmacology of the opioid peptides, enkephalins and endorphins. In the guinea-pig ileum methionine-enkephalin, normorphine and morphine are equipotent in depressing electrically evoked contractions; leucine-enkephalin has about 25% of the activity. The mouse vas deferens is more sensitive to the enkephalins which are 30 to 60 times more potent than morphine. Fragments of beta-lipotropin61-91 (beta-endorphin) having sequences up to LPH76 are more potent in the mouse vas deferens than in the guinea-pig ileum but beta-endorphin is about equipotent in the two preparations. None of the peptides has antagonist activity. Methionine-enkephalin and normorphine are equipotent in inhibiting [3H]-naloxone binding by homogenate of guinea-pig brain in the absence of Na+ while leucine-enkephalin has only 25% of this activity. In the guinea-pig ileum, naloxone antagonises normorhine and the enkephalins equally well whereas in the mouse vas deferens about ten times more naloxone is required for the enkophalins that for normorphine. Methionine-enkephalin depresses output of acetylcholine in the guinea-pig ileum and of noradrenaline in the mouse vas deferens."}
{"id": "PMID:17541", "title": "The role of adrenoceptors in norepinephrine-stimulated VO2 in muscle.", "content": "The purpose of this study was to characterize the norepinephrine (NE)-evoked calorigenic response of an isolated perfused rat muscle preparation into alpha-and/or beta-adrenergic components. Epinephrine was as effective as NE in evoking the increase in oxygen consumption. The alpha-agonist, phenylephrine, was also as effective as NE in eliciting an increase in oxygen consumption by the muscle. Isoproterenol (beta-agonist) had no effect on the VO2 of the preparation. Phentolamine, an alpha-blocker, completely blocked the NE-stimulated VO2. Propranolol (beta-antagonist) could also completely block the NE induced VO2 but this drug was found to be less potent. It was concluded that the NE-induced calorigenic response of muscle cannot be classified either strictly as an alpha-or beta-response, but unlike brown adipose tissue, the alpha-response seems to predominate in skeletal muscle. Also, it appears as though different mechanisms of action may be involved in the NE-stimulated VO2 in skeletal muscle and brown fat.", "contents": "The role of adrenoceptors in norepinephrine-stimulated VO2 in muscle. The purpose of this study was to characterize the norepinephrine (NE)-evoked calorigenic response of an isolated perfused rat muscle preparation into alpha-and/or beta-adrenergic components. Epinephrine was as effective as NE in evoking the increase in oxygen consumption. The alpha-agonist, phenylephrine, was also as effective as NE in eliciting an increase in oxygen consumption by the muscle. Isoproterenol (beta-agonist) had no effect on the VO2 of the preparation. Phentolamine, an alpha-blocker, completely blocked the NE-stimulated VO2. Propranolol (beta-antagonist) could also completely block the NE induced VO2 but this drug was found to be less potent. It was concluded that the NE-induced calorigenic response of muscle cannot be classified either strictly as an alpha-or beta-response, but unlike brown adipose tissue, the alpha-response seems to predominate in skeletal muscle. Also, it appears as though different mechanisms of action may be involved in the NE-stimulated VO2 in skeletal muscle and brown fat."}
{"id": "PMID:17544", "title": "[Effect of a schedule of administration of chlorpromazine, majeptil and trisedyl on the synthesis of proteins in different brain structures of rats].", "content": "Following a course-wise introduction of chlorpromazine, majeptil and trisedyl to rats the methionine-35S incorporation in the protein was diminished in most of the brain segments.", "contents": "[Effect of a schedule of administration of chlorpromazine, majeptil and trisedyl on the synthesis of proteins in different brain structures of rats]. Following a course-wise introduction of chlorpromazine, majeptil and trisedyl to rats the methionine-35S incorporation in the protein was diminished in most of the brain segments."}
{"id": "PMID:17545", "title": "[Effect of nonachlazine on the processes of uptake and release of nordrenaline].", "content": "Nonachlazine (2 micrometer) blocked significantly the uptake 1 of endogenic noradrenaline in the myocardial tissues and in adrenergic neurons of vas deferens. The uptake II, as well as the intensity and dynamics of the noradrenaline release were not affected by nonachlazine. These processes resulted in an increase of free noradrenaline concentrations in the synaptic space. The latter seems to be a result of the mediator's passage into the nerve fibers (through axonal membranes) and into the granule, this being due to the nonachlazine-induced block. It is suggested that the metabolic and functional nonachlazine effects are related to the beta-adrenergic receptors stimulation, mediated through the agency of noradrenaline.", "contents": "[Effect of nonachlazine on the processes of uptake and release of nordrenaline]. Nonachlazine (2 micrometer) blocked significantly the uptake 1 of endogenic noradrenaline in the myocardial tissues and in adrenergic neurons of vas deferens. The uptake II, as well as the intensity and dynamics of the noradrenaline release were not affected by nonachlazine. These processes resulted in an increase of free noradrenaline concentrations in the synaptic space. The latter seems to be a result of the mediator's passage into the nerve fibers (through axonal membranes) and into the granule, this being due to the nonachlazine-induced block. It is suggested that the metabolic and functional nonachlazine effects are related to the beta-adrenergic receptors stimulation, mediated through the agency of noradrenaline."}
{"id": "PMID:17547", "title": "[Stabilization of biological membranes with various acetylene amines].", "content": "In experiments with mitochondrial membranes and membranes of the endoplasmatic reticulum of the rats' liver the membrane-stabilizing action of a number of unsaturated amines was evaluated. The acetylene compounds studied reduced the extent of the membranes damage following UV-irradiation, treatment with detergents and their incubation in a hypoosmotic medium. Such an action displayed gutimine and sovcaine. Hydrated compounds, analogues of acetylene amines are devoid of the ability to raise the resistance of the cellular organoids membranes to damaging factors", "contents": "[Stabilization of biological membranes with various acetylene amines]. In experiments with mitochondrial membranes and membranes of the endoplasmatic reticulum of the rats' liver the membrane-stabilizing action of a number of unsaturated amines was evaluated. The acetylene compounds studied reduced the extent of the membranes damage following UV-irradiation, treatment with detergents and their incubation in a hypoosmotic medium. Such an action displayed gutimine and sovcaine. Hydrated compounds, analogues of acetylene amines are devoid of the ability to raise the resistance of the cellular organoids membranes to damaging factors"}
{"id": "PMID:17546", "title": "[Study of the induction of thrombocyte adhesiveness in the presence of heparin].", "content": "An investigation of the thrombocytes adhesion after Hellem (1960) showed that \"in vitro\" tests norepinephrine, epinephrine, histamine, serotonin and adenosine-diphosphate, when used in doses of 100-25,0 gamma/ml, were capable of raising the thrombocytes adhesion, while heparin administered in doses of 0.5-0.05 U/ml depressed and in a dose of 0.025 U/ml mildly activated this capacity of the thrombocytes. In the presence of heparin the ability of biogenic amines to induce the adhesion of thrombocytes decreased. Between concentration of the agents and the adhesive index of thrombocytes there exists a two-way logarithmic relationship. Intravenous administration of serotonin in a dose of 5 mg/kg and of epinephrine in an amount of 0.05 mg/kg to rabbits increased the adhesivity of thrombocytes, whereas intravenous introduction of 100 un/kg of heparin tended to greatly reduce it. On introduction of serotonin and epinephrine to rabbits against the background of heparin their ability to activate the thrombocytes adhesion diminished quite significantly. The logarithm of time lapsed from the instance of the heparin administration is linearly dependent on the  logarithms of values characterizing the adhesivity of thrombocytes. Intravenous administration of norepinephrine and histamine in a dose of 0.5 mg/kg did not cause any changes in the adhesive properties of thrombocytes.", "contents": "[Study of the induction of thrombocyte adhesiveness in the presence of heparin]. An investigation of the thrombocytes adhesion after Hellem (1960) showed that \"in vitro\" tests norepinephrine, epinephrine, histamine, serotonin and adenosine-diphosphate, when used in doses of 100-25,0 gamma/ml, were capable of raising the thrombocytes adhesion, while heparin administered in doses of 0.5-0.05 U/ml depressed and in a dose of 0.025 U/ml mildly activated this capacity of the thrombocytes. In the presence of heparin the ability of biogenic amines to induce the adhesion of thrombocytes decreased. Between concentration of the agents and the adhesive index of thrombocytes there exists a two-way logarithmic relationship. Intravenous administration of serotonin in a dose of 5 mg/kg and of epinephrine in an amount of 0.05 mg/kg to rabbits increased the adhesivity of thrombocytes, whereas intravenous introduction of 100 un/kg of heparin tended to greatly reduce it. On introduction of serotonin and epinephrine to rabbits against the background of heparin their ability to activate the thrombocytes adhesion diminished quite significantly. The logarithm of time lapsed from the instance of the heparin administration is linearly dependent on the  logarithms of values characterizing the adhesivity of thrombocytes. Intravenous administration of norepinephrine and histamine in a dose of 0.5 mg/kg did not cause any changes in the adhesive properties of thrombocytes."}
{"id": "PMID:17557", "title": "A double-blind trial of penbutolol: a new beta-receptor blocking agent in the treatment of angina pectoris.", "content": "A double-blind placebo controlled study of angina pectoris with penbutolol was undertaken in parallel groups in fifty-two patients. The duration of the study was six weeks. The dosage range for penbutolol was 8 mg to 50 mg per day. Six patients were dropped from the analysis. Seventeen patients (81%) in the penbutolol series exhibited a 50% reduction in anginal attacks, NTG consumption and subjective improvement. Significant reduction in nitrite intake was observed. Effort tolerance was improved significantly in those receiving penbutolol. Penbutolol was well-tolerated.", "contents": "A double-blind trial of penbutolol: a new beta-receptor blocking agent in the treatment of angina pectoris. A double-blind placebo controlled study of angina pectoris with penbutolol was undertaken in parallel groups in fifty-two patients. The duration of the study was six weeks. The dosage range for penbutolol was 8 mg to 50 mg per day. Six patients were dropped from the analysis. Seventeen patients (81%) in the penbutolol series exhibited a 50% reduction in anginal attacks, NTG consumption and subjective improvement. Significant reduction in nitrite intake was observed. Effort tolerance was improved significantly in those receiving penbutolol. Penbutolol was well-tolerated."}
{"id": "PMID:17558", "title": "A trial of benorylate tablets in the symptomatic relief of osteoarthritis.", "content": "The effectiveness of Benoral Tablets in controlling joint pain and stiffness in osteoarthritis was assessed over a two-week period in a multicentre general practice open study. In this trial it has been demonstrated that a correlation exists between pain relief from stiffness for patients suffering from osteoarthritis taking Benoral Tablets over this period. It was also found that patients with initially mild to moderate pain benefited most from their treatment.", "contents": "A trial of benorylate tablets in the symptomatic relief of osteoarthritis. The effectiveness of Benoral Tablets in controlling joint pain and stiffness in osteoarthritis was assessed over a two-week period in a multicentre general practice open study. In this trial it has been demonstrated that a correlation exists between pain relief from stiffness for patients suffering from osteoarthritis taking Benoral Tablets over this period. It was also found that patients with initially mild to moderate pain benefited most from their treatment."}
{"id": "PMID:17559", "title": "Polygraphic sleep recordings before and after the administration of flunitrazepam.", "content": "By means of polygraphic sleep recordings (EEG, EOG, EMG, ECG, EDG, Respirogram, Positogram), neurologic-psychologic investigation and questionnaires on subjective feeling, ten patients aged from 22 to 40 years (mean: 29 years), who suffered from irregular disturbances in falling asleep and in sleeping continuously, were examined over a period of ten consecutives nights. The first investigation night was reserved for adaptation of the patients and could therefore not be evaluated. On the following three evenings placebo (Placebo I) was given, then 2 mg of flunitrazepam for the ensuing three nights and placebo again (Placebo II) for the last three nights. Thus, 90 investigation nights could be evaluated. 1. Latency times until the patients fell asleep and up to the first deep sleep were reduced significantly by the active preparation. Latency times up to the first REM-phase were prolonged. 2. The frequency of nocturnal awakenings was lessened significantly. Thus, disturbances in sleeping continuously disappeared for the duration of the treatment. Duration of wakefulness after having woken during the night decreased considerably. 3. Duration of wakefulness during the total night was reduced considerably, deeper sleep stages, such as D (stage III) and E(stage IV) were prolonged. 4. Duration of the REM-phases was reduced slightly. This reduction was not significant according to the t-test. 5. According to these results, the preparation showed a clear effect. A placebo-effect can be excluded, since the improvements mentioned were not found when placebo was given before administration of the medication and afterwards (Placebo I and II). 6. When comparing our results to those of other authors, who described the effects of various preparations, we found that the substance flunitrazepam showed different effects.", "contents": "Polygraphic sleep recordings before and after the administration of flunitrazepam. By means of polygraphic sleep recordings (EEG, EOG, EMG, ECG, EDG, Respirogram, Positogram), neurologic-psychologic investigation and questionnaires on subjective feeling, ten patients aged from 22 to 40 years (mean: 29 years), who suffered from irregular disturbances in falling asleep and in sleeping continuously, were examined over a period of ten consecutives nights. The first investigation night was reserved for adaptation of the patients and could therefore not be evaluated. On the following three evenings placebo (Placebo I) was given, then 2 mg of flunitrazepam for the ensuing three nights and placebo again (Placebo II) for the last three nights. Thus, 90 investigation nights could be evaluated. 1. Latency times until the patients fell asleep and up to the first deep sleep were reduced significantly by the active preparation. Latency times up to the first REM-phase were prolonged. 2. The frequency of nocturnal awakenings was lessened significantly. Thus, disturbances in sleeping continuously disappeared for the duration of the treatment. Duration of wakefulness after having woken during the night decreased considerably. 3. Duration of wakefulness during the total night was reduced considerably, deeper sleep stages, such as D (stage III) and E(stage IV) were prolonged. 4. Duration of the REM-phases was reduced slightly. This reduction was not significant according to the t-test. 5. According to these results, the preparation showed a clear effect. A placebo-effect can be excluded, since the improvements mentioned were not found when placebo was given before administration of the medication and afterwards (Placebo I and II). 6. When comparing our results to those of other authors, who described the effects of various preparations, we found that the substance flunitrazepam showed different effects."}
{"id": "PMID:17563", "title": "Effect of secretin on plasma motilin in man.", "content": "Graded doses of 0-1, 0-3, 0-9, and 2-7 clinical units/kg/h of pure synthetic secretin were infused over 60 minute periods in six healthy volunteers. Duodenal bicarbonate output and pH were recorded and plasma secretin and motilin levels were measured by radioimmunoassay. During the infusions plasma motilin fell in a dose dependent manner to a nadir of 35%. This fall was linearly correlated with pancreatic bicarbonate output, whereas a non-linear correlation was observed between plasma motilin and both plasma secretin level and duodenal pH. It is suggested that plasma motilin levels are decreased by secretin-induced pancreatic bicarbonate juice flow. This may be important for the control of motilin secretion initiated by duodenal acidification and the concomitant delay in gastric emptying.", "contents": "Effect of secretin on plasma motilin in man. Graded doses of 0-1, 0-3, 0-9, and 2-7 clinical units/kg/h of pure synthetic secretin were infused over 60 minute periods in six healthy volunteers. Duodenal bicarbonate output and pH were recorded and plasma secretin and motilin levels were measured by radioimmunoassay. During the infusions plasma motilin fell in a dose dependent manner to a nadir of 35%. This fall was linearly correlated with pancreatic bicarbonate output, whereas a non-linear correlation was observed between plasma motilin and both plasma secretin level and duodenal pH. It is suggested that plasma motilin levels are decreased by secretin-induced pancreatic bicarbonate juice flow. This may be important for the control of motilin secretion initiated by duodenal acidification and the concomitant delay in gastric emptying."}
{"id": "PMID:17564", "title": "Jejunal mucosal gamma glutamyl transferase activity in coeliac disease.", "content": "In view of data suggesting that deficiency of gamma glutamyl transferase (GGT) may be the primary abnormality in the small-intestinal mucosa of patients with coeliac disease, this enzyme was measured in mucosal biopsies from coeliac patients at different stages of treatment. Activity was only slightly reduced in only one of nine well-treated patients, suggesting that deficiency of this enzyme has no primary role in the aetiology of coeliac disease.", "contents": "Jejunal mucosal gamma glutamyl transferase activity in coeliac disease. In view of data suggesting that deficiency of gamma glutamyl transferase (GGT) may be the primary abnormality in the small-intestinal mucosa of patients with coeliac disease, this enzyme was measured in mucosal biopsies from coeliac patients at different stages of treatment. Activity was only slightly reduced in only one of nine well-treated patients, suggesting that deficiency of this enzyme has no primary role in the aetiology of coeliac disease."}
{"id": "PMID:17565", "title": "Correlation between manometric and pH tests for gastro-oesophageal reflux.", "content": "A series of tests, including gastro-oesophageal sphincter pressure measurement, short-term pH tests, and 15-hour overnight oesophageal pH recording were applied to 42 normal subjects and 214 patients with typical reflux symptoms. The results were compared by multivariate discriminant analysis. Sphincter pressure measurements misclassified 32%, stressed provocative manoeuvres 14-5%, and the best single discriminator from the overnight pH study was time below pH 5, which misclassified 13%. However, a combination of the number of reflux episodes in 15 hours with their mean duration reduced misclassification to 8-8%. Using this function, a boundary between normal and reflux can be drawn, and the degree of abnormality can be expressed visually as well as numerically.", "contents": "Correlation between manometric and pH tests for gastro-oesophageal reflux. A series of tests, including gastro-oesophageal sphincter pressure measurement, short-term pH tests, and 15-hour overnight oesophageal pH recording were applied to 42 normal subjects and 214 patients with typical reflux symptoms. The results were compared by multivariate discriminant analysis. Sphincter pressure measurements misclassified 32%, stressed provocative manoeuvres 14-5%, and the best single discriminator from the overnight pH study was time below pH 5, which misclassified 13%. However, a combination of the number of reflux episodes in 15 hours with their mean duration reduced misclassification to 8-8%. Using this function, a boundary between normal and reflux can be drawn, and the degree of abnormality can be expressed visually as well as numerically."}
{"id": "PMID:17567", "title": "[Utilization of the MVA-immunization schedule from the view point of the public health service].", "content": "The world-wide smallpox eradication program sponsored by the WHO has been successful. Furthermore the legislation regarding smallpox vaccination in the Federal Republic of Germany has been given a new form. The place of the previous mass-vaccination has been taken by vaccination of individuals. Under this aspect safe procedures for vaccination are required. Any vaccination used by Public Health Service has to fulfill the following criteria: High protection against the disease without adverse side-effects or risks; it should be simple to administer and applicable under ordinary circumstances. For primary vaccination against smallpox the MVA-vaccination meets these demands entirely. It is reported about own experiences with 700 vaccinations using the attenuated virus \"MVA\"; complete documentation is given. Not a single complication nor any adverse side-effects have been seen. The Public Health Service has gained great experience in the field of vaccination. It is responsible for the protection of the individual as well as the public, as it is undesirable that there develops and unvaccinated group within the population. The individual claim a complete protection through vaccination which should be absolutely free of any risk.", "contents": "[Utilization of the MVA-immunization schedule from the view point of the public health service]. The world-wide smallpox eradication program sponsored by the WHO has been successful. Furthermore the legislation regarding smallpox vaccination in the Federal Republic of Germany has been given a new form. The place of the previous mass-vaccination has been taken by vaccination of individuals. Under this aspect safe procedures for vaccination are required. Any vaccination used by Public Health Service has to fulfill the following criteria: High protection against the disease without adverse side-effects or risks; it should be simple to administer and applicable under ordinary circumstances. For primary vaccination against smallpox the MVA-vaccination meets these demands entirely. It is reported about own experiences with 700 vaccinations using the attenuated virus \"MVA\"; complete documentation is given. Not a single complication nor any adverse side-effects have been seen. The Public Health Service has gained great experience in the field of vaccination. It is responsible for the protection of the individual as well as the public, as it is undesirable that there develops and unvaccinated group within the population. The individual claim a complete protection through vaccination which should be absolutely free of any risk."}
{"id": "PMID:17572", "title": "Characteristics of the maternal lymphoid response of mice to paternal strain antigens induced by homologous pregnancy.", "content": "Mice mated with H-2 incompatible males were shown to have an increased frequency of specific allocluster-forming spleen cells to paternal strain erythrocytes. The time course of the response was similar to that expected following a skin allograft. The graft-versus-host responsiveness of the maternal lymphocytes was generally elevated in the post-partum period in matings with males incompatible at either the H2 locus or non-H2 loci. The implications of these responses with respect to their different lymphocyte mediators and possible interactions are discussed with the view that a B-cell mediated immune response to paternal antigens may be contributory to foetal survival.", "contents": "Characteristics of the maternal lymphoid response of mice to paternal strain antigens induced by homologous pregnancy. Mice mated with H-2 incompatible males were shown to have an increased frequency of specific allocluster-forming spleen cells to paternal strain erythrocytes. The time course of the response was similar to that expected following a skin allograft. The graft-versus-host responsiveness of the maternal lymphocytes was generally elevated in the post-partum period in matings with males incompatible at either the H2 locus or non-H2 loci. The implications of these responses with respect to their different lymphocyte mediators and possible interactions are discussed with the view that a B-cell mediated immune response to paternal antigens may be contributory to foetal survival."}
{"id": "PMID:17574", "title": "Identification, separation, and preliminary characterization of invertase and beta-galactosidase in Actinomyces viscosus.", "content": "The initial step of disaccharide dissimilation by Actinomyces viscosus serotype 2 strain M-100 was studied. Sucrase activity was found in the 3,000 X g particulate fraction and the 37,000 X g soluble fraction of the cells, whereas lactase activity was found almost exclusively in the 37,000 X g soluble fraction. Neither sucrase nor lactase activity was appreciable in the culture liquor. Sucrose phosphorylase, alpha-glucosidase, and polysaccharide synthesis activities were not observed in the soluble cell fraction. The sucrase was identified as invertase (EC 3.2.1.26; beta-D-fructofuranoside fructohydrolase). The lactase was identified as beta-galactosidase (EC 3.2.1.23; beta-D-galactoside galactohydrolase). The enzymes in the 37,000 X g soluble fraction were separable by diethylamino-ethyl-cellulose chromatography, giving one beta-galactosidase peak and one major and one minor invertase peak. Acrylamide gel electrophoresis showed different electrophoretic mobilities of the enzymes. The molecular weight of the beta-galactosidase is about 4.2 X 10(5) and that of invertase is about 8.6 X 10(4). The beta-galactosidase has a Km for lactose of about 6 mM and a pH optimum between pH 6.0 and 6.5. The major invertase component has a Km for sucrose of about 71 mM and a pH optimum between pH 5.8 and 6.3.", "contents": "Identification, separation, and preliminary characterization of invertase and beta-galactosidase in Actinomyces viscosus. The initial step of disaccharide dissimilation by Actinomyces viscosus serotype 2 strain M-100 was studied. Sucrase activity was found in the 3,000 X g particulate fraction and the 37,000 X g soluble fraction of the cells, whereas lactase activity was found almost exclusively in the 37,000 X g soluble fraction. Neither sucrase nor lactase activity was appreciable in the culture liquor. Sucrose phosphorylase, alpha-glucosidase, and polysaccharide synthesis activities were not observed in the soluble cell fraction. The sucrase was identified as invertase (EC 3.2.1.26; beta-D-fructofuranoside fructohydrolase). The lactase was identified as beta-galactosidase (EC 3.2.1.23; beta-D-galactoside galactohydrolase). The enzymes in the 37,000 X g soluble fraction were separable by diethylamino-ethyl-cellulose chromatography, giving one beta-galactosidase peak and one major and one minor invertase peak. Acrylamide gel electrophoresis showed different electrophoretic mobilities of the enzymes. The molecular weight of the beta-galactosidase is about 4.2 X 10(5) and that of invertase is about 8.6 X 10(4). The beta-galactosidase has a Km for lactose of about 6 mM and a pH optimum between pH 6.0 and 6.5. The major invertase component has a Km for sucrose of about 71 mM and a pH optimum between pH 5.8 and 6.3."}
{"id": "PMID:17576", "title": "Corneal transplantation reaction in avascular keratoconus patients due to HLA-associated immune aberration against infection. A hypothesis.", "content": "HLA-B12 and HLA-B27 appeared to be characteristic of avascular keratoconus patients at risk of developing a corneal allograft reaction, which was mainly of late type and triggered by a nasopharyngeal infection. Equally incompatible grafts to patients with HLA-B5 had an uneventful course. This may be inference to the role of HLA-associated immune resistance factors, which necessitate the search for histocompatible corneal grafts also for avascular recipients bearing such indicators of risk.", "contents": "Corneal transplantation reaction in avascular keratoconus patients due to HLA-associated immune aberration against infection. A hypothesis. HLA-B12 and HLA-B27 appeared to be characteristic of avascular keratoconus patients at risk of developing a corneal allograft reaction, which was mainly of late type and triggered by a nasopharyngeal infection. Equally incompatible grafts to patients with HLA-B5 had an uneventful course. This may be inference to the role of HLA-associated immune resistance factors, which necessitate the search for histocompatible corneal grafts also for avascular recipients bearing such indicators of risk."}
{"id": "PMID:17578", "title": "Hepatic microsomal enzyme induction and its evaluation in a clinical laboratory.", "content": "We tried to determine whether short-term treatment with alpha-methyldopa, quinidine, digoxin, diazepam or furosemide--drugs in common use in hospitals--is capable of stimulating the activity of hepatic microsomal drug-metabolizing enzymes. Glucaric acid (GA) excretion and serum activity of gamma-glutamyl transpeptidase (GGT) were used as indicators of hepatic microsomal enzyme activity. Increased GA excretion was found in 45% and increased serum GGT activity in 40% of the patients on drug treatment. Only 14.3% showed an increase in both indicators. The excretion of GA rose significantly in patients who received drugs for less than 10 days, as compared with those who received drugs for less than 10 days, whereas the percentage of high GGT values did not rise significantly with increased duration of treatment. The lack of correlation between serum GGT activity and GA excretion casts doubt on the value of GGT as a consistent indicator of microsomal enzyme induction. GA excretion, on the other hand, seems to be a dependable index of microsomal enzyme induction in response to short-term treatment with standard doses of several widely used drugs.", "contents": "Hepatic microsomal enzyme induction and its evaluation in a clinical laboratory. We tried to determine whether short-term treatment with alpha-methyldopa, quinidine, digoxin, diazepam or furosemide--drugs in common use in hospitals--is capable of stimulating the activity of hepatic microsomal drug-metabolizing enzymes. Glucaric acid (GA) excretion and serum activity of gamma-glutamyl transpeptidase (GGT) were used as indicators of hepatic microsomal enzyme activity. Increased GA excretion was found in 45% and increased serum GGT activity in 40% of the patients on drug treatment. Only 14.3% showed an increase in both indicators. The excretion of GA rose significantly in patients who received drugs for less than 10 days, as compared with those who received drugs for less than 10 days, whereas the percentage of high GGT values did not rise significantly with increased duration of treatment. The lack of correlation between serum GGT activity and GA excretion casts doubt on the value of GGT as a consistent indicator of microsomal enzyme induction. GA excretion, on the other hand, seems to be a dependable index of microsomal enzyme induction in response to short-term treatment with standard doses of several widely used drugs."}
{"id": "PMID:17573", "title": "The interaction of barbiturates and analeptics.", "content": "The interaction of pentobarbitone sodium with three analeptics viz. micoren, pentylenetetrazol and methedrine was studied in mice. Micoren prolonged pentobarbitone sleeping time. pentylenetetrazol shortened the sleeping time. Methedrine also shortened the sleeping time, but clonic convulsions of mild to severe intensity were noticed 45-60 minutes after the drug injection.", "contents": "The interaction of barbiturates and analeptics. The interaction of pentobarbitone sodium with three analeptics viz. micoren, pentylenetetrazol and methedrine was studied in mice. Micoren prolonged pentobarbitone sleeping time. pentylenetetrazol shortened the sleeping time. Methedrine also shortened the sleeping time, but clonic convulsions of mild to severe intensity were noticed 45-60 minutes after the drug injection."}
{"id": "PMID:17579", "title": "[Unusually high gamma-glutamyltransferase level in the semen and ist diagnostic significance].", "content": "A remarkable high activity of the enzyme gamma-glutamyltransferase (gamma-GT) is found in seminal fluid in 200 to 500 fold higher concentrations as found in blood serum. The seminal fluid gamma-GT originates expecially in the prostate gland and, to a smaller extent, in spermatozoa and secretion of testis and epididymis. Gamma-GT could be valuable to investigate the function of the prostate gland.", "contents": "[Unusually high gamma-glutamyltransferase level in the semen and ist diagnostic significance]. A remarkable high activity of the enzyme gamma-glutamyltransferase (gamma-GT) is found in seminal fluid in 200 to 500 fold higher concentrations as found in blood serum. The seminal fluid gamma-GT originates expecially in the prostate gland and, to a smaller extent, in spermatozoa and secretion of testis and epididymis. Gamma-GT could be valuable to investigate the function of the prostate gland."}
{"id": "PMID:17575", "title": "Aids for in vitro Mycobacterium lepraemurium investigations: estimation of oxidation-reduction potentials and pO2 with 2, 6 dichlorophenol indophenol.", "content": "The partial success in cultivating a \"host-dependent\" microbe provided the incentive to develop methods which may aid the growth of the organism. The oxidation-reduction potential (ORP) of NC-5, an aerobic, cysteine containing medium which supports the limited in vitro growth of Mycobacterium lepraemurium, is measurable with the redox dye, 2, 6 dichlorophenol indophenol. Both cysteine and autoclaved glucose can be used to adjust to ORP. Glucose autoclaved in phosphate buffer but not in aqueous solutions reduced the dye. The dye was also reduced in glucose solutions by atmospheres containing 10% and 1%-2% pO2. With exposure to 20% pO2 the reoxidation of the dye was slow but complete. Thus, the dye in glucose solutions provides a general method for estimating pO2 above the level of anaerobiosis. Proper adjustment and monitoring of the ORP and pO2 may enhance growth.", "contents": "Aids for in vitro Mycobacterium lepraemurium investigations: estimation of oxidation-reduction potentials and pO2 with 2, 6 dichlorophenol indophenol. The partial success in cultivating a \"host-dependent\" microbe provided the incentive to develop methods which may aid the growth of the organism. The oxidation-reduction potential (ORP) of NC-5, an aerobic, cysteine containing medium which supports the limited in vitro growth of Mycobacterium lepraemurium, is measurable with the redox dye, 2, 6 dichlorophenol indophenol. Both cysteine and autoclaved glucose can be used to adjust to ORP. Glucose autoclaved in phosphate buffer but not in aqueous solutions reduced the dye. The dye was also reduced in glucose solutions by atmospheres containing 10% and 1%-2% pO2. With exposure to 20% pO2 the reoxidation of the dye was slow but complete. Thus, the dye in glucose solutions provides a general method for estimating pO2 above the level of anaerobiosis. Proper adjustment and monitoring of the ORP and pO2 may enhance growth."}
{"id": "PMID:17580", "title": "[Microchemical investigation of alpha D-glucosidases using 4-methylumnelliferyl- and 2-naphthyl-alpha-d-glucoside (author's transl)].", "content": "In crude homogenates prepared from freeze-dried cryostate sections of various rat organs the Km and Vmax of acid and neutral alpha-glucosidase as well as the effect of the pH, substrate and enzyme concentration and the incubation time on the activity were determined fluorometrically with 4-methylumbelliferyl- and 2-naphthyl alpha-d-glucoside as substrates. On the basis of the biochemical data 2 assays were developed for the microchemical measurement of both alpha-glucosidases in groups of epithelial cells isolated from freeze dried cryostate sections of the epididymis, jejunum, ilium, liver and kidney of suckling and adult rats. The rate of hydrolysis of 2-naphthyl and 4-methylumbelliferyl alpha-d-glucoside differs moderately. However, due to the higher sensitivity of 4-methylumbelliferone the methylumbelliferyl derivative is preferable especially for the evaluation of alpha-d-glucosidases in cells with low enzyme activity.", "contents": "[Microchemical investigation of alpha D-glucosidases using 4-methylumnelliferyl- and 2-naphthyl-alpha-d-glucoside (author's transl)]. In crude homogenates prepared from freeze-dried cryostate sections of various rat organs the Km and Vmax of acid and neutral alpha-glucosidase as well as the effect of the pH, substrate and enzyme concentration and the incubation time on the activity were determined fluorometrically with 4-methylumbelliferyl- and 2-naphthyl alpha-d-glucoside as substrates. On the basis of the biochemical data 2 assays were developed for the microchemical measurement of both alpha-glucosidases in groups of epithelial cells isolated from freeze dried cryostate sections of the epididymis, jejunum, ilium, liver and kidney of suckling and adult rats. The rate of hydrolysis of 2-naphthyl and 4-methylumbelliferyl alpha-d-glucoside differs moderately. However, due to the higher sensitivity of 4-methylumbelliferone the methylumbelliferyl derivative is preferable especially for the evaluation of alpha-d-glucosidases in cells with low enzyme activity."}
{"id": "PMID:17585", "title": "Nursing education in crisis: a computer alternative.", "content": "The impact of computer-assisted instruction upon the educational process is having its effect. The computer is being used in nursing education today to manage the educational environment, to instruct, to evaluate, to identify problem areas, to gather data, to manipulate data for research purposes and for continued education. As we struggle in our efforts for quality individualized education, we are minutely scrutinizing every aspect of the teaching learning process. We are not only examining how we teach but what we teach and why we are teaching it! Our deeper understanding of the process of education has helped us to delineate nursing process as content. Higher levels of instructional goals -- cognitive, affective and conative -- are resulting in education of the whole individual. The systematization of the learning process with the greater ease of accountability is leading nursing education to blaze promising new trails into the twenty-first century.", "contents": "Nursing education in crisis: a computer alternative. The impact of computer-assisted instruction upon the educational process is having its effect. The computer is being used in nursing education today to manage the educational environment, to instruct, to evaluate, to identify problem areas, to gather data, to manipulate data for research purposes and for continued education. As we struggle in our efforts for quality individualized education, we are minutely scrutinizing every aspect of the teaching learning process. We are not only examining how we teach but what we teach and why we are teaching it! Our deeper understanding of the process of education has helped us to delineate nursing process as content. Higher levels of instructional goals -- cognitive, affective and conative -- are resulting in education of the whole individual. The systematization of the learning process with the greater ease of accountability is leading nursing education to blaze promising new trails into the twenty-first century."}
{"id": "PMID:17589", "title": "Using the computer to prepare multiple-choice examinations: a simplified system.", "content": "Program TEST offers a quick, easy, and efficient way to produce objectively-scored exams from an established item bank. It is especially useful in situations where frequent testing is utilized and secretarial help is scarce. The capability of constructing a customized exam the day before its administration should make the exam more reflective of the instruction. The provision for keyed copies has been found to be a useful tool for feedback to the student after the exam. Lastly, use of the program requires little computer assistance.", "contents": "Using the computer to prepare multiple-choice examinations: a simplified system. Program TEST offers a quick, easy, and efficient way to produce objectively-scored exams from an established item bank. It is especially useful in situations where frequent testing is utilized and secretarial help is scarce. The capability of constructing a customized exam the day before its administration should make the exam more reflective of the instruction. The provision for keyed copies has been found to be a useful tool for feedback to the student after the exam. Lastly, use of the program requires little computer assistance."}
{"id": "PMID:17593", "title": "Itaconate, an isocitrate lyase-directed inhibitor in Pseudomonas indigofera.", "content": "Enzymes catalyzing steps from ethanol to acetyl-coenzyme A, from malate to pyruvate, and from pyruvate to glucose 6-phosphate were identified in ethanol-grown Pseudomonas indigofera. Enzymes catalyzing the catabolism of glucose to pyruvate via the Entner-Doudoroff pathway were identified in glucose-grown cells. Phosphofructokinase could not be detected in Pseudomonas indigofera. Itaconate, a potent inhibitor of isocitrate lyase, abolished growth of P. indigofera on ethanol at concentrations that had little effect upon growth on glucose. The date obtained through enzyme analyses and studies of itaconate inhibition with both extracts and toluene-treated cells suggest that itaconate selectively inhibits and reduces the specific activity of isocitrate lyase.", "contents": "Itaconate, an isocitrate lyase-directed inhibitor in Pseudomonas indigofera. Enzymes catalyzing steps from ethanol to acetyl-coenzyme A, from malate to pyruvate, and from pyruvate to glucose 6-phosphate were identified in ethanol-grown Pseudomonas indigofera. Enzymes catalyzing the catabolism of glucose to pyruvate via the Entner-Doudoroff pathway were identified in glucose-grown cells. Phosphofructokinase could not be detected in Pseudomonas indigofera. Itaconate, a potent inhibitor of isocitrate lyase, abolished growth of P. indigofera on ethanol at concentrations that had little effect upon growth on glucose. The date obtained through enzyme analyses and studies of itaconate inhibition with both extracts and toluene-treated cells suggest that itaconate selectively inhibits and reduces the specific activity of isocitrate lyase."}
{"id": "PMID:17594", "title": "Chemotaxis toward amino acids by Bdellovibrio bacteriovorus.", "content": "Chemotaxis toward amino acids by Bdellovibrio bacteriovorous strain UKi2 was studied by the capillary technique of Adler (J. Gen. Microbiol. 74:77-91, 1973). Chemotaxis was shown to be optimal when the capillaries were incubated at between 15 and 40 degrees C for 30 min; the optimal pH was between 7.0 and 8.2. The chemotactic response was proportional to the density of the suspension of bdellovibrios up to a density of 10(8) cells/ml. B. bacteriovorus was attracted to L-asparagine, L-cysteine, L-glutamine, glycine, L-histidine, L-lysine, and L-threonine. The possible roles of chemotaxis in the life of B. bacteriovorus are discussed.", "contents": "Chemotaxis toward amino acids by Bdellovibrio bacteriovorus. Chemotaxis toward amino acids by Bdellovibrio bacteriovorous strain UKi2 was studied by the capillary technique of Adler (J. Gen. Microbiol. 74:77-91, 1973). Chemotaxis was shown to be optimal when the capillaries were incubated at between 15 and 40 degrees C for 30 min; the optimal pH was between 7.0 and 8.2. The chemotactic response was proportional to the density of the suspension of bdellovibrios up to a density of 10(8) cells/ml. B. bacteriovorus was attracted to L-asparagine, L-cysteine, L-glutamine, glycine, L-histidine, L-lysine, and L-threonine. The possible roles of chemotaxis in the life of B. bacteriovorus are discussed."}
{"id": "PMID:17595", "title": "Fructose 1,6-diphosphate-activated L-lactate dehydrogenase from Streptococcus lactis: kinetic properties and factors affecting activation.", "content": "The L-(+)-lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) of Streptococcus lactis C10, like that of other streptococci, was activated by fructose 1,6-diphosphate (FDP). The enzyme showed some activity in the absence of FDP, with a pH optimum of 8.2; FDP decreased the Km for both pyruvate and reduced nicotinamide adenine dinucleotide (NADH) and shifted the pH optimum to 6.9. Enzyme activity showed a hyperbolic response to both NADH and pyruvate in all the buffers tried except phosphate buffer, in which the response to increasing NADH was sigmoidal. The FDP concentration required for half-maximal velocity (FDP0.5V) was markedly influenced by the nature of the assay buffer used. Thus the FDP0.5V was 0.002 mM in 90 mM triethanolamine buffer, 0.2 mM in 90 mM tris(hydroxymethyl)aminomethanemaleate buffer, and 4.4 mM in 90 mM phosphate buffer. Phosphate inhibition of FDP binding is not a general property of streptococcal lactate dehydrogenase, since the FDP0.5V value for S. faecalis 8043 lactate dehydrogenase was not increased by phosphate. The S. faecalis and S. lactis lactate dehydrogenases also differed in that Mn2+ enhanced FDP binding in S. faecalis but had no effect on the S. lactis dehydrogenase. The FDP concentration (12 to 15 mM) found in S. lactis cells during logarithmic growth on a high-carbohydrate (3% lactose) medium would be adequate to give almost complete activation of the lactate dehydrogenase even if the high FDP0.5V value found in 90 mM phosphate were similar to the FDP requirement in vivo.", "contents": "Fructose 1,6-diphosphate-activated L-lactate dehydrogenase from Streptococcus lactis: kinetic properties and factors affecting activation. The L-(+)-lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) of Streptococcus lactis C10, like that of other streptococci, was activated by fructose 1,6-diphosphate (FDP). The enzyme showed some activity in the absence of FDP, with a pH optimum of 8.2; FDP decreased the Km for both pyruvate and reduced nicotinamide adenine dinucleotide (NADH) and shifted the pH optimum to 6.9. Enzyme activity showed a hyperbolic response to both NADH and pyruvate in all the buffers tried except phosphate buffer, in which the response to increasing NADH was sigmoidal. The FDP concentration required for half-maximal velocity (FDP0.5V) was markedly influenced by the nature of the assay buffer used. Thus the FDP0.5V was 0.002 mM in 90 mM triethanolamine buffer, 0.2 mM in 90 mM tris(hydroxymethyl)aminomethanemaleate buffer, and 4.4 mM in 90 mM phosphate buffer. Phosphate inhibition of FDP binding is not a general property of streptococcal lactate dehydrogenase, since the FDP0.5V value for S. faecalis 8043 lactate dehydrogenase was not increased by phosphate. The S. faecalis and S. lactis lactate dehydrogenases also differed in that Mn2+ enhanced FDP binding in S. faecalis but had no effect on the S. lactis dehydrogenase. The FDP concentration (12 to 15 mM) found in S. lactis cells during logarithmic growth on a high-carbohydrate (3% lactose) medium would be adequate to give almost complete activation of the lactate dehydrogenase even if the high FDP0.5V value found in 90 mM phosphate were similar to the FDP requirement in vivo."}
{"id": "PMID:17596", "title": "On the apparent inhibition of intramolecular activation of pepsinogen by pepsin substrates.", "content": "Marciniszyn et al. (Marciniszyn, J., Huang, J. S. Hartsuch, J. A., Tang, J. (1976) J. Biol. Chem. 251, 7095-7102) have recently suggested an intermediate in the intramolecular activation of pepsinogen. As evidence, they showed apparent competitive inhibition of activation by globin, indication a pepsinogen-globin complex. Previous work had shown pepsinogen activation to occur very rapidly in the presence of high concentrations of hemoglobin, a very similar pepsin substrate (McPhie, P. (1974) Biochem. Biophys. Res. Commun. 56, 789-792). This contradiction has been resolved by a re-evaluation of the techniques used in the two investigations. The experimental conditions of Marciniszyn et al. Were inadequately defined to ensure denaturation of pepsin, a prerequisite of their method. A small decrease in pH, caused by the presence of extraneous protein, prevents this denaturation and leads to consistent underestimates of the rate of zymogen activation.", "contents": "On the apparent inhibition of intramolecular activation of pepsinogen by pepsin substrates. Marciniszyn et al. (Marciniszyn, J., Huang, J. S. Hartsuch, J. A., Tang, J. (1976) J. Biol. Chem. 251, 7095-7102) have recently suggested an intermediate in the intramolecular activation of pepsinogen. As evidence, they showed apparent competitive inhibition of activation by globin, indication a pepsinogen-globin complex. Previous work had shown pepsinogen activation to occur very rapidly in the presence of high concentrations of hemoglobin, a very similar pepsin substrate (McPhie, P. (1974) Biochem. Biophys. Res. Commun. 56, 789-792). This contradiction has been resolved by a re-evaluation of the techniques used in the two investigations. The experimental conditions of Marciniszyn et al. Were inadequately defined to ensure denaturation of pepsin, a prerequisite of their method. A small decrease in pH, caused by the presence of extraneous protein, prevents this denaturation and leads to consistent underestimates of the rate of zymogen activation."}
{"id": "PMID:17600", "title": "Circular dichroic and perturbation spectra of aromatic chromophores in rabbit tropomyosin. Topography of tyrosine residues.", "content": "1. Difference spectra of tryosyl residues obtained on denaturation of tropomycosin with urea or guanidinium chloride indicate that strong hydrophobic environments exist in the native coiled-coil state. 2. Solvent perturbation difference spectra indicate that tyrosyl residues are partially accessible to the solvent. The accessiblity decreases with increasing size of the solvent molecules. 3. Spectral pH titration of tyrosyl residues cannot provide information on the tyrosyl accessibility because conformational change accompanies the increase in pH. 4. Circular dichroism of tyrosyl and phenylalanyl residues is consistent with the effect of imposed conformational rigidity on the partially asymmetrical vibrational fine structure of the 1Lb absorption band of phenyl and benzyl chromophores; the effect is reduced by 70% on unfolding of tropomyosin.", "contents": "Circular dichroic and perturbation spectra of aromatic chromophores in rabbit tropomyosin. Topography of tyrosine residues. 1. Difference spectra of tryosyl residues obtained on denaturation of tropomycosin with urea or guanidinium chloride indicate that strong hydrophobic environments exist in the native coiled-coil state. 2. Solvent perturbation difference spectra indicate that tyrosyl residues are partially accessible to the solvent. The accessiblity decreases with increasing size of the solvent molecules. 3. Spectral pH titration of tyrosyl residues cannot provide information on the tyrosyl accessibility because conformational change accompanies the increase in pH. 4. Circular dichroism of tyrosyl and phenylalanyl residues is consistent with the effect of imposed conformational rigidity on the partially asymmetrical vibrational fine structure of the 1Lb absorption band of phenyl and benzyl chromophores; the effect is reduced by 70% on unfolding of tropomyosin."}
{"id": "PMID:17605", "title": "Purification and properties of tRNA(adenine-1)-methyltransferase from rat liver.", "content": "An S-adenosylmethionine-dependent tRNA(adenine-1)-methyltransferase has been purified 8,000-fold from rat liver. This preparation gives a single band on polyacrylamide gel electrophoresis and is stable in long term storage. The enzyme has a molecular weight of approximately 95,000. The single methylating capacity of this adenine-1 methyltransferase, using Escherichia coli tRNA2Glu, is methylation of the invariant adenine in the GTpsiC loop. The methylation reaction is dependent on added cation with 20 to 40 mM putrescine being most effective. The Km for S-adenosylmethionine was found to be 0.3 micron, while the Ki for the product inhibitor S-adenosylhomocysteine was 0.85 micron. The Km for tRNAMetf is 12 nM while that for tRNAGlu2 is 33 nM.", "contents": "Purification and properties of tRNA(adenine-1)-methyltransferase from rat liver. An S-adenosylmethionine-dependent tRNA(adenine-1)-methyltransferase has been purified 8,000-fold from rat liver. This preparation gives a single band on polyacrylamide gel electrophoresis and is stable in long term storage. The enzyme has a molecular weight of approximately 95,000. The single methylating capacity of this adenine-1 methyltransferase, using Escherichia coli tRNA2Glu, is methylation of the invariant adenine in the GTpsiC loop. The methylation reaction is dependent on added cation with 20 to 40 mM putrescine being most effective. The Km for S-adenosylmethionine was found to be 0.3 micron, while the Ki for the product inhibitor S-adenosylhomocysteine was 0.85 micron. The Km for tRNAMetf is 12 nM while that for tRNAGlu2 is 33 nM."}
{"id": "PMID:17606", "title": "PZ-peptidase from chick embryos. Purification, properties, and action on collagen peptides.", "content": "PZ-peptidase is an endopeptidase that cleaves the synthetic substrate developed for clostridial collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (PZ-peptide). The peptidase has been purified to homogeneity from chicken embryos. The enzyme has a pH optimum of 7.5 to 8.5, and isoelectric point of 5.0, and a molecular weight of 77,000. The kinetic parameters at pH 8 and 37 degrees are: Km = 2 X 10(-4) M and Vmax = 4.2 mumol/min/mg of protein. The enzyme is inhibited by p-hydroxymercuribenzoate (100%), N-ethylmaleimide (60%), and chelating agents (40 to 60%). Maximum activity is attained in the presence of reducing agents and Ca2+, Sr2+, or Mg2+. The peptidase has no detectable action on casein, serum albumin, collagen, collagen alpha chains, various collagen peptides (alpha1)(I)-CB2, alpha1(I)-CB3, alpha1(I)-CB4), (Gly-Pro-Pro)10, or (Gly-Pro-Pro)5. It does catalyze the hydrolysis of the Hyp--Gly bond in the 17-residue collagen peptide alpha1(II)-CB6-C2 and it partially digested a mixture of collagen peptides of molecular weight 350 to 2500. A role of this peptidase in collagen breakdown appears to be restricted to a late stage when degradation products would fall in the range of 5 to 30 residues.", "contents": "PZ-peptidase from chick embryos. Purification, properties, and action on collagen peptides. PZ-peptidase is an endopeptidase that cleaves the synthetic substrate developed for clostridial collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (PZ-peptide). The peptidase has been purified to homogeneity from chicken embryos. The enzyme has a pH optimum of 7.5 to 8.5, and isoelectric point of 5.0, and a molecular weight of 77,000. The kinetic parameters at pH 8 and 37 degrees are: Km = 2 X 10(-4) M and Vmax = 4.2 mumol/min/mg of protein. The enzyme is inhibited by p-hydroxymercuribenzoate (100%), N-ethylmaleimide (60%), and chelating agents (40 to 60%). Maximum activity is attained in the presence of reducing agents and Ca2+, Sr2+, or Mg2+. The peptidase has no detectable action on casein, serum albumin, collagen, collagen alpha chains, various collagen peptides (alpha1)(I)-CB2, alpha1(I)-CB3, alpha1(I)-CB4), (Gly-Pro-Pro)10, or (Gly-Pro-Pro)5. It does catalyze the hydrolysis of the Hyp--Gly bond in the 17-residue collagen peptide alpha1(II)-CB6-C2 and it partially digested a mixture of collagen peptides of molecular weight 350 to 2500. A role of this peptidase in collagen breakdown appears to be restricted to a late stage when degradation products would fall in the range of 5 to 30 residues."}
{"id": "PMID:17607", "title": "Studies on cobalt myoglobins and hemoglobins. Interaction of sperm whale myoglobin and Glycera hemoglobin with molecular oxygen.", "content": "The pH dependence of the electron paramagnetic resonance (EPR) spectrum and oxygen affinity of cobaltous porphyrin-containing myoglobin (CoMb) have been examined. The hyperfine structures of the EPR spectrum of oxy-CoMb undergo small, reversible pH-dependent changes with pK values of 5.33, 5.55, and 5.25 +/- 0.05 for proto-, meso-, and deutero-CoMb's, respectively, whereas deoxy-CoMb does not exhibit any pH dependence of its EPR spectrum. The partial pressure of oxygen at half-saturation of proto-CoMb decreases from 26 to 42 Torr on lowering the pH from 7.0 to 4.8. For comparison, we have prepared cobaltous porphyrin-containing monomeric Glycera hemoglobin (CoHb (Glycera)), in which the distal histidyl group of myoglobin is replaced by a leucyl residue, and examined the equilibria and kinetics of its oxygenation and EPR spectrum. CoHb (Glycera) has exhibited a very low oxygen affinity (p50 = 7 X 10(2) Torr at 5 degrees) and a large dissociation rate constant (more than 8 X 10(4) S-1 at 5 degrees). The EPR spectrum of oxy-CoHb (Glycera) was affected by neither pH nor replacement of H2O with D2O. Low temperature photodissociation studies by EPR and spectrophotometry have shown that the photolyzed form of the ligated hemoglobin (Glycera) is similar to its deoxy form, in contrast to myoglobin which gives a new intermediate states as the photolyzed form. These differences between CoMb and CoHb (Glycera) are interpreted with relation to the possible role of the distal histidyl residue in CoMb.", "contents": "Studies on cobalt myoglobins and hemoglobins. Interaction of sperm whale myoglobin and Glycera hemoglobin with molecular oxygen. The pH dependence of the electron paramagnetic resonance (EPR) spectrum and oxygen affinity of cobaltous porphyrin-containing myoglobin (CoMb) have been examined. The hyperfine structures of the EPR spectrum of oxy-CoMb undergo small, reversible pH-dependent changes with pK values of 5.33, 5.55, and 5.25 +/- 0.05 for proto-, meso-, and deutero-CoMb's, respectively, whereas deoxy-CoMb does not exhibit any pH dependence of its EPR spectrum. The partial pressure of oxygen at half-saturation of proto-CoMb decreases from 26 to 42 Torr on lowering the pH from 7.0 to 4.8. For comparison, we have prepared cobaltous porphyrin-containing monomeric Glycera hemoglobin (CoHb (Glycera)), in which the distal histidyl group of myoglobin is replaced by a leucyl residue, and examined the equilibria and kinetics of its oxygenation and EPR spectrum. CoHb (Glycera) has exhibited a very low oxygen affinity (p50 = 7 X 10(2) Torr at 5 degrees) and a large dissociation rate constant (more than 8 X 10(4) S-1 at 5 degrees). The EPR spectrum of oxy-CoHb (Glycera) was affected by neither pH nor replacement of H2O with D2O. Low temperature photodissociation studies by EPR and spectrophotometry have shown that the photolyzed form of the ligated hemoglobin (Glycera) is similar to its deoxy form, in contrast to myoglobin which gives a new intermediate states as the photolyzed form. These differences between CoMb and CoHb (Glycera) are interpreted with relation to the possible role of the distal histidyl residue in CoMb."}
{"id": "PMID:17608", "title": "Lipid A mutants of Salmonella typhimurium. Purification and characterization of a lipid A precursor produced by a mutant in 3-deoxy-D-mannooctulosonate-8-phosphate synthetase.", "content": "We describe here the isolation, purification, and structural characterization of a lipid A precursor synthesized under nonpermissive conditions by a mutant of Salmonella typhimurium conditionally defective in the synthesis of the 3-deoxy-D-mannoctulosonate (2-keto-3-deoxyoctonate, KDO) region of the lipopolysaccharide. The precursor was isolated free from lipopolysaccharide, murein, and phospholipids by extraction of delipidated cells with 90% phenol/CHCL3/petroleum ether. The molecule was recovered from the phenol phase after precipitation of lipopolysaccharide with H2O and subsequently purified by DEAE-cellulose chromatography. Structural analyses showed that the lipid A precursor is a phosphorylated glucosamine disaccharide containing one ester and two amide-linked residues of beta-hydroxymyristate. In contrast to lipid A, the precursor disaccharide lacks ester-linked 12:0 and 14:0 fatty acids as well as KDO. The molecule contains 2 phosphate residues both of which were identified as phosphomonoesters by 31P NMR spectroscopy. One of the phosphomonoesters is located in position 1 of the reducing terminal glucosamine residue; the location of the other phosphomonoester was not determined. The structure of the precursor provides strong support for the conclusion that KDO incorporation occurs at an early stage in lipid A biosynthesis prior to the incorporation of ester-linked saturated fatty acids.", "contents": "Lipid A mutants of Salmonella typhimurium. Purification and characterization of a lipid A precursor produced by a mutant in 3-deoxy-D-mannooctulosonate-8-phosphate synthetase. We describe here the isolation, purification, and structural characterization of a lipid A precursor synthesized under nonpermissive conditions by a mutant of Salmonella typhimurium conditionally defective in the synthesis of the 3-deoxy-D-mannoctulosonate (2-keto-3-deoxyoctonate, KDO) region of the lipopolysaccharide. The precursor was isolated free from lipopolysaccharide, murein, and phospholipids by extraction of delipidated cells with 90% phenol/CHCL3/petroleum ether. The molecule was recovered from the phenol phase after precipitation of lipopolysaccharide with H2O and subsequently purified by DEAE-cellulose chromatography. Structural analyses showed that the lipid A precursor is a phosphorylated glucosamine disaccharide containing one ester and two amide-linked residues of beta-hydroxymyristate. In contrast to lipid A, the precursor disaccharide lacks ester-linked 12:0 and 14:0 fatty acids as well as KDO. The molecule contains 2 phosphate residues both of which were identified as phosphomonoesters by 31P NMR spectroscopy. One of the phosphomonoesters is located in position 1 of the reducing terminal glucosamine residue; the location of the other phosphomonoester was not determined. The structure of the precursor provides strong support for the conclusion that KDO incorporation occurs at an early stage in lipid A biosynthesis prior to the incorporation of ester-linked saturated fatty acids."}
{"id": "PMID:17609", "title": "Role of coenzyme in aminotransferase turnover.", "content": "The role of coenzyme in determining intracellular contnet of pyridoxal enzymes was assessed by analyzing effects of pyridoxine deficiency on the rapidly degraded, readily dissociable tyrosine aminotransferase (EC 2.6.1.5) and the slowly degraded, nondissociable alanine aminotransferase (EC 2.6.1.2) of rat liver. Synthesis of the tyrosine enzyme was reduced, leading to a decreased amount of this enzyme, much of which was present as active apoenzyme. Synthesis of alanine aminotransferase was unchanged but much of this enzyme was present as an inactive apoenzyme which retained immunological reactivity. Degradation rates of both enzymes (t1/2 about 1.5 h, tyrosine aminotransferase; about 3 days, alanine aminotransferase) were not changed in pyridoxine deficiency. Hence, interaction with coenzyme is not a significant determinant in intracellular degradation of these aminotransferases. Coenzymes dissociation and intracellular stability probably reflect structural features of the proteins which determine both properties.", "contents": "Role of coenzyme in aminotransferase turnover. The role of coenzyme in determining intracellular contnet of pyridoxal enzymes was assessed by analyzing effects of pyridoxine deficiency on the rapidly degraded, readily dissociable tyrosine aminotransferase (EC 2.6.1.5) and the slowly degraded, nondissociable alanine aminotransferase (EC 2.6.1.2) of rat liver. Synthesis of the tyrosine enzyme was reduced, leading to a decreased amount of this enzyme, much of which was present as active apoenzyme. Synthesis of alanine aminotransferase was unchanged but much of this enzyme was present as an inactive apoenzyme which retained immunological reactivity. Degradation rates of both enzymes (t1/2 about 1.5 h, tyrosine aminotransferase; about 3 days, alanine aminotransferase) were not changed in pyridoxine deficiency. Hence, interaction with coenzyme is not a significant determinant in intracellular degradation of these aminotransferases. Coenzymes dissociation and intracellular stability probably reflect structural features of the proteins which determine both properties."}
{"id": "PMID:17611", "title": "In vitro reconstitution of demolybdosulfite oxidase by molybdate.", "content": "Reconstitution of purified demolybdosulfite oxidase from rat liver has been achieved using inorganic molybdate as the source of molybdenum. The activation process has a pH optimum of 7.4 and is dependent on concentrations of molybdate and demolybdoenzyme. The reaction is inhibited by high concentrations of anions and by reduction of the demolybdoenzyme and requires incubation temperatures higher than 30 degrees. A reconstitution mechanism involving loss of tungsten and concomitant replacement with molybdenum in those demolybdo molecules which contain tungsten is supported by the following observations: (a) the extent of activation achieved by molybdate corresponds to the proportion of molecules in the preparation which contain tungsten. (b) Incubation of the demolybdoenzyme preparation at 37 degrees in the absence of molybdate results in progressive and concentration-dependent loss of ability to be reconstituted by molybdate and a corresponding but more rapid loss of tungsten from the enzyme. The reconstituted enzyme displays the molybdenum EPR signal characteristic of native enzyme and is inactivated by incubation at 42 degrees in a manner identical to native sulfite oxidase.", "contents": "In vitro reconstitution of demolybdosulfite oxidase by molybdate. Reconstitution of purified demolybdosulfite oxidase from rat liver has been achieved using inorganic molybdate as the source of molybdenum. The activation process has a pH optimum of 7.4 and is dependent on concentrations of molybdate and demolybdoenzyme. The reaction is inhibited by high concentrations of anions and by reduction of the demolybdoenzyme and requires incubation temperatures higher than 30 degrees. A reconstitution mechanism involving loss of tungsten and concomitant replacement with molybdenum in those demolybdo molecules which contain tungsten is supported by the following observations: (a) the extent of activation achieved by molybdate corresponds to the proportion of molecules in the preparation which contain tungsten. (b) Incubation of the demolybdoenzyme preparation at 37 degrees in the absence of molybdate results in progressive and concentration-dependent loss of ability to be reconstituted by molybdate and a corresponding but more rapid loss of tungsten from the enzyme. The reconstituted enzyme displays the molybdenum EPR signal characteristic of native enzyme and is inactivated by incubation at 42 degrees in a manner identical to native sulfite oxidase."}
{"id": "PMID:17615", "title": "Lacerations of the flexor hallucis longus in the young athlete.", "content": "Of ten patients with lacerations of the flexor hallucis longus tendon, nine were athletically inclined. In four, the laceration was not repaired and no disability was evident. A functioning flexor hallucis longus, therefore, does not seem to be essential for good push-off and balance in running sports. If both the flexor hallucis brevis and the flexor hallucis longus are lacerated and reconstitution of the longus is not possible, the brevis should be repaired, suturing the distal segment of the longus to brevis to prevent hyperextension deformity of the metatarsophalangeal joint. Hypersensitivity of the scar due to associated nerve injury is a frequent complication associated with laceration of the flexor hallucis longus.", "contents": "Lacerations of the flexor hallucis longus in the young athlete. Of ten patients with lacerations of the flexor hallucis longus tendon, nine were athletically inclined. In four, the laceration was not repaired and no disability was evident. A functioning flexor hallucis longus, therefore, does not seem to be essential for good push-off and balance in running sports. If both the flexor hallucis brevis and the flexor hallucis longus are lacerated and reconstitution of the longus is not possible, the brevis should be repaired, suturing the distal segment of the longus to brevis to prevent hyperextension deformity of the metatarsophalangeal joint. Hypersensitivity of the scar due to associated nerve injury is a frequent complication associated with laceration of the flexor hallucis longus."}
{"id": "PMID:17616", "title": "Effects of cytosine arabinoside on differential gene expression in embryonic neural retina. II. Immunochemical studies on the accumulation of glutamine synthetase.", "content": "Cytosine arabinoside (Ara-C) elicits a significant increase in the level of the enzyme glutamine synthetase (GS) while it markedly reduces overall RNA and protein synthesis in cultures of embryonic chick neural retina. This increase was analyzed by radioimmunochemical procedures and compared with the induction of GS by hydrocortisone (HC). Accumulation of GS in Ara-C-treated retinas was found to be due to de novo synthesis of the enzyme; however, unlike the induction of GS by HC, Ara-C caused no measurable increase in the rate of GS synthesis. The results indicate that Ara-C facilitates GS accumulation largely by preventing degradation of the enzyme. Even though Ara-C inhibits the bulk of RNA synthesis in the retina, it does not stop the formation of GS-specific RNA templates. However, the progressive accumulation of these templates does not result in an increased rate of GS synthesis unless Ara-C is withdrawn from such cultures under suitable experimental conditions. Thus, it is suggested that the continuous presence of Ara-C imposes a reversible hindrance at the translational level which limits the rate of GS synthesis. The results demonstrate that the increase in retinal GS elicited by Ara-C is achieved through mechanisms which are quite different from those involved in the hydrocortisone-mediated induction of this enzyme.", "contents": "Effects of cytosine arabinoside on differential gene expression in embryonic neural retina. II. Immunochemical studies on the accumulation of glutamine synthetase. Cytosine arabinoside (Ara-C) elicits a significant increase in the level of the enzyme glutamine synthetase (GS) while it markedly reduces overall RNA and protein synthesis in cultures of embryonic chick neural retina. This increase was analyzed by radioimmunochemical procedures and compared with the induction of GS by hydrocortisone (HC). Accumulation of GS in Ara-C-treated retinas was found to be due to de novo synthesis of the enzyme; however, unlike the induction of GS by HC, Ara-C caused no measurable increase in the rate of GS synthesis. The results indicate that Ara-C facilitates GS accumulation largely by preventing degradation of the enzyme. Even though Ara-C inhibits the bulk of RNA synthesis in the retina, it does not stop the formation of GS-specific RNA templates. However, the progressive accumulation of these templates does not result in an increased rate of GS synthesis unless Ara-C is withdrawn from such cultures under suitable experimental conditions. Thus, it is suggested that the continuous presence of Ara-C imposes a reversible hindrance at the translational level which limits the rate of GS synthesis. The results demonstrate that the increase in retinal GS elicited by Ara-C is achieved through mechanisms which are quite different from those involved in the hydrocortisone-mediated induction of this enzyme."}
{"id": "PMID:17618", "title": "Modulation of in vitro erythropoiesis. The influence of beta-adrenergic agonists on erythroid colony formation.", "content": "Canine marrow erythroid colony growth is enhanced by agents linked to the adenyl cyclase/cyclic AMP (cAMP) system, including cAMP, a phosphodieterase inhibitor (RO-20-1724), cholera enterotoxin, and beta-adrenergic agonists. The adrenergic effect is mediated by receptors having beta2-subspecificity. These receptors are distinct from putative receptors for erythropoietin and those acted upon by cholera enterotoxin. In addition, the population of cells most responsive to beta-agonists is distinct from the majority of erythropoientin-responsive cells, perhaps representing a subpopulation of this class of cell. This demonstration of an adenyl cyclase-linked mechanism regulating mammalian erythroid colony growth provides a model for the modulation by other hormones or small molecules of in vitro and, perhaps, in vivo erythropoiesis.", "contents": "Modulation of in vitro erythropoiesis. The influence of beta-adrenergic agonists on erythroid colony formation. Canine marrow erythroid colony growth is enhanced by agents linked to the adenyl cyclase/cyclic AMP (cAMP) system, including cAMP, a phosphodieterase inhibitor (RO-20-1724), cholera enterotoxin, and beta-adrenergic agonists. The adrenergic effect is mediated by receptors having beta2-subspecificity. These receptors are distinct from putative receptors for erythropoietin and those acted upon by cholera enterotoxin. In addition, the population of cells most responsive to beta-agonists is distinct from the majority of erythropoientin-responsive cells, perhaps representing a subpopulation of this class of cell. This demonstration of an adenyl cyclase-linked mechanism regulating mammalian erythroid colony growth provides a model for the modulation by other hormones or small molecules of in vitro and, perhaps, in vivo erythropoiesis."}
{"id": "PMID:17619", "title": "Effect of ascorbic acid on arylsulfatase activities and sulfated proteoglycan metabolism in chondrocyte cultures.", "content": "A correlation between increased arylsulfatase activities and decreased sulfated proteoglycan content in human osteoarthritic articular cartilage suggested a possible interrelationship between these parameters. Since we had previously shown that ascorbate caused a decrease in levels of arylsulfatase A and B activities in normal chondrocyte cultures, the validity of the above relationship was examined by measuring the effect of vitamin C on the biosynthesis and distribution of 35S-labeled proteoglycans and arylsulfatase A and B activities in cell extracts of chondrocytes derived from normal and osteoarthritic tissue. Arylsulfatase A and B activities were found to be reduced in the presence of ascorbic acid in all normal and osteoarthritic cell lines examined when measured 3, 6, 10, and 13 days after the introduction of the vitamin in the culture medium. Acid phosphatase activity, on the other hand, was found to be elevated in the presence of ascorbate. The inhibitory effect by ascorbic acid on arylsulfatase activities could be reversed by withdrawing the vitamin from the nutrient medium. Addition of EDTA to the cell extracts before assay also reversed the inhibiton. Sulfated proteoglycan biosynthesis as reflected in 35S-sulfate uptake per milligram of DNA was significantly increased in the presence of ascorbic acid. The distribution of the newly synthesized molecules between the cell layer and medium fractions was altered. In the presence of ascorbate, more deposition into the cell layer of newly synthesized macromolecules occurred. These data suggest an inverse relationship between arylsulfatase activities and the stability of the newly synthesized sulfated proteoglycans in the extracellular matrix.", "contents": "Effect of ascorbic acid on arylsulfatase activities and sulfated proteoglycan metabolism in chondrocyte cultures. A correlation between increased arylsulfatase activities and decreased sulfated proteoglycan content in human osteoarthritic articular cartilage suggested a possible interrelationship between these parameters. Since we had previously shown that ascorbate caused a decrease in levels of arylsulfatase A and B activities in normal chondrocyte cultures, the validity of the above relationship was examined by measuring the effect of vitamin C on the biosynthesis and distribution of 35S-labeled proteoglycans and arylsulfatase A and B activities in cell extracts of chondrocytes derived from normal and osteoarthritic tissue. Arylsulfatase A and B activities were found to be reduced in the presence of ascorbic acid in all normal and osteoarthritic cell lines examined when measured 3, 6, 10, and 13 days after the introduction of the vitamin in the culture medium. Acid phosphatase activity, on the other hand, was found to be elevated in the presence of ascorbate. The inhibitory effect by ascorbic acid on arylsulfatase activities could be reversed by withdrawing the vitamin from the nutrient medium. Addition of EDTA to the cell extracts before assay also reversed the inhibiton. Sulfated proteoglycan biosynthesis as reflected in 35S-sulfate uptake per milligram of DNA was significantly increased in the presence of ascorbic acid. The distribution of the newly synthesized molecules between the cell layer and medium fractions was altered. In the presence of ascorbate, more deposition into the cell layer of newly synthesized macromolecules occurred. These data suggest an inverse relationship between arylsulfatase activities and the stability of the newly synthesized sulfated proteoglycans in the extracellular matrix."}
{"id": "PMID:17620", "title": "Studies on the mechanism of ristocetin-induced platelet agglutination. Effects of structural modification of ristocetin and vancomycin.", "content": "The mechanism by which ristocetin induces platelet agglutination in the presence of the von Willebrand factor was studied by chemically altering ristocetin and a similar antibiotic, vancomycin, by reaction with a water-soluble carbodiimide in the presence of glycine methyl ester at pH 4.75. Altering ristocetin's phenolic groups (which are thought to be important in its peptide-binding properties) resulted in a loss of both platelet-agglutinating and antibiotic activities. Restoring the phenolic groups with hydroxylamine restored both activities. Vancomycin has antibiotic and peptide-binding properties similar to ristocetin's, but differs structurally in having a free carboxyl group and thus a less positive charge at neutral pH. It does not induce platelet agglutination and actually inhibits ristocetin-induced agglutination. Reacting vancomycin with the water-soluble carbodiimide resulted in alteration of phenolic groups and permanent conversion of the carboxyl to a neutral derivative. Restoring the phenolic groups with hydroxylamine (but leaving the carboxyl neutralized) produced a compound with charge properties similar to ristocetin's which induced platelet agglutination as ristocetin does. These data suggest both a binding requirement (mediated through phenolic groups) and a strong positive charge requirement for ristocetin-induced agglutination. The data are consistent with a model wherein positively charged ristocetin binds, via its phenolic groups, to sites on the platelet surface and reduces the platelet's negative charge. This could reduce the electrostatic repulsion between platelets and/or between platelets and the negatively charged von Willebrand factor, and permit the macromolecular von Willebrand factor to cause agglutination by bridging between platelets.", "contents": "Studies on the mechanism of ristocetin-induced platelet agglutination. Effects of structural modification of ristocetin and vancomycin. The mechanism by which ristocetin induces platelet agglutination in the presence of the von Willebrand factor was studied by chemically altering ristocetin and a similar antibiotic, vancomycin, by reaction with a water-soluble carbodiimide in the presence of glycine methyl ester at pH 4.75. Altering ristocetin's phenolic groups (which are thought to be important in its peptide-binding properties) resulted in a loss of both platelet-agglutinating and antibiotic activities. Restoring the phenolic groups with hydroxylamine restored both activities. Vancomycin has antibiotic and peptide-binding properties similar to ristocetin's, but differs structurally in having a free carboxyl group and thus a less positive charge at neutral pH. It does not induce platelet agglutination and actually inhibits ristocetin-induced agglutination. Reacting vancomycin with the water-soluble carbodiimide resulted in alteration of phenolic groups and permanent conversion of the carboxyl to a neutral derivative. Restoring the phenolic groups with hydroxylamine (but leaving the carboxyl neutralized) produced a compound with charge properties similar to ristocetin's which induced platelet agglutination as ristocetin does. These data suggest both a binding requirement (mediated through phenolic groups) and a strong positive charge requirement for ristocetin-induced agglutination. The data are consistent with a model wherein positively charged ristocetin binds, via its phenolic groups, to sites on the platelet surface and reduces the platelet's negative charge. This could reduce the electrostatic repulsion between platelets and/or between platelets and the negatively charged von Willebrand factor, and permit the macromolecular von Willebrand factor to cause agglutination by bridging between platelets."}
{"id": "PMID:17621", "title": "Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease.", "content": "In normal plasma, the ratio of the procoagulant activity of factor VIII (VIII(AHF)) to that of the von Willebrand factor activity (ristocetin cofactor, VIII(VWF)) or factor VIII antigen (VIII(AGN)) is approximately 1, but ratios > 1 (e.g., VIII(AHF) > VIII(VWF) or VIII(AGN)) may be observed in some patients with von Willebrand's disease and in the \"late\" posttransfusion plasmas of patients with this disorder. The lability of VIII(AHF) was studied by incubating plasma, diluted 1:10 in imidazole buffer pH 7.1, for 6 h at 37 degrees C. With normal plasmas, 77+/-12% (SD) of the original VIII(AHF) activity remained after incubation. VIII(AHF) was labile (e.g., 35-55% residual activity) in the \"late\" posttransfusion plasmas (VIII(AHF) >> VIII(VWF)) of a patient with von Willebrand's disease, but not in the \"early\" posttransfusion plasmas (VIII(AHF) approximately VIII(VWF)). VIII(AHF) was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIII(AHF) to VIII(VWF) were 4.4 to 8.1, but not in the plasmas of four other patients in whom the ratio was approximately 1. The electrophoretic mobility of factor VIII antigen was increased in two of the three patients with labile VIII(AHF). In both of these patients, and in the late posttransfusion plasmas, labile VIII(AHF) activity could be stabilized by the addition of purified von Willebrand factor (lacking VIII(AHF) activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIII(VWF) may serve to stabilize VIII(AHF) and this might explain the posttransfusion findings in von Willebrand's disease.", "contents": "Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease. In normal plasma, the ratio of the procoagulant activity of factor VIII (VIII(AHF)) to that of the von Willebrand factor activity (ristocetin cofactor, VIII(VWF)) or factor VIII antigen (VIII(AGN)) is approximately 1, but ratios > 1 (e.g., VIII(AHF) > VIII(VWF) or VIII(AGN)) may be observed in some patients with von Willebrand's disease and in the \"late\" posttransfusion plasmas of patients with this disorder. The lability of VIII(AHF) was studied by incubating plasma, diluted 1:10 in imidazole buffer pH 7.1, for 6 h at 37 degrees C. With normal plasmas, 77+/-12% (SD) of the original VIII(AHF) activity remained after incubation. VIII(AHF) was labile (e.g., 35-55% residual activity) in the \"late\" posttransfusion plasmas (VIII(AHF) >> VIII(VWF)) of a patient with von Willebrand's disease, but not in the \"early\" posttransfusion plasmas (VIII(AHF) approximately VIII(VWF)). VIII(AHF) was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIII(AHF) to VIII(VWF) were 4.4 to 8.1, but not in the plasmas of four other patients in whom the ratio was approximately 1. The electrophoretic mobility of factor VIII antigen was increased in two of the three patients with labile VIII(AHF). In both of these patients, and in the late posttransfusion plasmas, labile VIII(AHF) activity could be stabilized by the addition of purified von Willebrand factor (lacking VIII(AHF) activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIII(VWF) may serve to stabilize VIII(AHF) and this might explain the posttransfusion findings in von Willebrand's disease."}
{"id": "PMID:17623", "title": "Central neurotransmitter substances and aging: a review.", "content": "Available evidence suggests that age is an important determinant of the levels of neurotransmitters and their associated enzymes and metabolites in some regions of the brain. Alterations at the synaptic level, or selective cell death in the brain, or both, may be implicated in progressive loss of function, behavioral changes and the onset of age-related diseases. Stimulation of hypothalamic neuroendocrine transducer cells by agents that alter neurotransmitter metabolism might provide some measure of control of the process of aging.", "contents": "Central neurotransmitter substances and aging: a review. Available evidence suggests that age is an important determinant of the levels of neurotransmitters and their associated enzymes and metabolites in some regions of the brain. Alterations at the synaptic level, or selective cell death in the brain, or both, may be implicated in progressive loss of function, behavioral changes and the onset of age-related diseases. Stimulation of hypothalamic neuroendocrine transducer cells by agents that alter neurotransmitter metabolism might provide some measure of control of the process of aging."}
{"id": "PMID:17626", "title": "The hydrolysis of Zectran in buffered and natural waters.", "content": "The analyses and rates of hydrolysis of Zectran, 4-dimethylamino-3,5-xylyl methylcarbamate are reported in aqueous media. These rates were measured in phosphate buffered, distilled water and in natural waters where tempteratures of 10 degrees, 20 degrees, and 28 degrees C. and pH values of 5.94, 7.00, and 8.42 were used. Intial concentrations of Zectran exceeded 60 mg/l (0.27 mMol 1(-1), whereas in the natural waters initial concentrations were 30 mg/l (0.135 mMol 1(-1). This study shows that the persistance of Zechtran in natural waters is, in large part, dependent upon the pH value and the temperature.", "contents": "The hydrolysis of Zectran in buffered and natural waters. The analyses and rates of hydrolysis of Zectran, 4-dimethylamino-3,5-xylyl methylcarbamate are reported in aqueous media. These rates were measured in phosphate buffered, distilled water and in natural waters where tempteratures of 10 degrees, 20 degrees, and 28 degrees C. and pH values of 5.94, 7.00, and 8.42 were used. Intial concentrations of Zectran exceeded 60 mg/l (0.27 mMol 1(-1), whereas in the natural waters initial concentrations were 30 mg/l (0.135 mMol 1(-1). This study shows that the persistance of Zechtran in natural waters is, in large part, dependent upon the pH value and the temperature."}
{"id": "PMID:17639", "title": "Immunofixation after electrofocusing: improved method for specific detection of serum proteins with determination of isoelectric points. I. Immunofixation print technique for detection of alpha-1-protease inhibitor.", "content": "An improved method is described for direct localization of human serum proteins in polyacrylamide gel with simultaneous determination of their isoelectric points (pI). The technique employs isoelectric focusing in thin-layer polyacrylamide gels to separate the serum proteins and the pH gradient is read at 4 degrees C with a dual-membrane surface microelectrode. Subsequently, the desired proteins are localized by immunofixation in the gel or by immunofixation-printing onto cellulose acetate strips soaked in specific antiserum. No sectioning of the electrofocused gel is necessary, and the entire technique can be completed in less than 14 h. When this method is applied to the detection of the genetic variants of alpha-1-antitrypsin (alpha-1-protease inhibitor) (A1Pi system), the results indicate that it can be used to specifically localize serum proteins whose pI's differ by as little as 0.01 pH units. The resolution afforded is especially evident in the analysis of A1Pi M variants.", "contents": "Immunofixation after electrofocusing: improved method for specific detection of serum proteins with determination of isoelectric points. I. Immunofixation print technique for detection of alpha-1-protease inhibitor. An improved method is described for direct localization of human serum proteins in polyacrylamide gel with simultaneous determination of their isoelectric points (pI). The technique employs isoelectric focusing in thin-layer polyacrylamide gels to separate the serum proteins and the pH gradient is read at 4 degrees C with a dual-membrane surface microelectrode. Subsequently, the desired proteins are localized by immunofixation in the gel or by immunofixation-printing onto cellulose acetate strips soaked in specific antiserum. No sectioning of the electrofocused gel is necessary, and the entire technique can be completed in less than 14 h. When this method is applied to the detection of the genetic variants of alpha-1-antitrypsin (alpha-1-protease inhibitor) (A1Pi system), the results indicate that it can be used to specifically localize serum proteins whose pI's differ by as little as 0.01 pH units. The resolution afforded is especially evident in the analysis of A1Pi M variants."}
{"id": "PMID:17640", "title": "Autonomic neuroeffector junctions--reflex vasodilatation of the skin.", "content": "A general model of the autonomic neuroeffector junction is proposed. In this model, emphasis is placed on the muscle effector bundle with electrotonic coupling between individual cells via gap junctions (or nexuses) and en passage release of transmitter from autonomic nerve varicosities. This release results in transmission to effector cells across junctional clefts ranging from about 20 nm in the vas deferens and iris to as much as 2000 nm in some large arteries. The ultrastructural identification of different autonomic nerve types is described. Current theories on the synthesis, storage, release, and inactivation of transmitter during cholinergic, adrenergic, and purinergic transmission are summarized. Some speculations are made about the possible involvement of purinergic nerves in the innervation of vessels and mast cells in the skin, and whether this involvement results in a functional link between ATP, histamine, bradykinin, and prostaglandin in cutaneous vasodilatation. Another possibility considered as the basis for this reflex is the release of substance P from sensory (pain) nerve collaterals in the skin.", "contents": "Autonomic neuroeffector junctions--reflex vasodilatation of the skin. A general model of the autonomic neuroeffector junction is proposed. In this model, emphasis is placed on the muscle effector bundle with electrotonic coupling between individual cells via gap junctions (or nexuses) and en passage release of transmitter from autonomic nerve varicosities. This release results in transmission to effector cells across junctional clefts ranging from about 20 nm in the vas deferens and iris to as much as 2000 nm in some large arteries. The ultrastructural identification of different autonomic nerve types is described. Current theories on the synthesis, storage, release, and inactivation of transmitter during cholinergic, adrenergic, and purinergic transmission are summarized. Some speculations are made about the possible involvement of purinergic nerves in the innervation of vessels and mast cells in the skin, and whether this involvement results in a functional link between ATP, histamine, bradykinin, and prostaglandin in cutaneous vasodilatation. Another possibility considered as the basis for this reflex is the release of substance P from sensory (pain) nerve collaterals in the skin."}
{"id": "PMID:17641", "title": "The Haarscheibe.", "content": "The Haarscheibe is a specialized spot of epidermis containing many Merkel cell-neurite complexes. It is a highly sensitive, slowly adapting, modality-specific touch receptor occurring in all mammals. Its exact role in signaling sensation in human beings is undetermined, and the function of Merkel cells, with their distinctive cytoplasmic granules, in transducing mechanical force into neural action potentials remains to be determined.", "contents": "The Haarscheibe. The Haarscheibe is a specialized spot of epidermis containing many Merkel cell-neurite complexes. It is a highly sensitive, slowly adapting, modality-specific touch receptor occurring in all mammals. Its exact role in signaling sensation in human beings is undetermined, and the function of Merkel cells, with their distinctive cytoplasmic granules, in transducing mechanical force into neural action potentials remains to be determined."}
{"id": "PMID:17642", "title": "Factors which influence blood platelet migration.", "content": "Migration of human blood platelets in vitro was investigated by a modification of the capillary-tube migration chamber technique used to study the migration inhibition factor of macrophages. Platelets were packed in capillary tubes and incubated in autologous platelet-free plasma (PFP). The extent of migration was quantified by planimetry (measurement of the area of platelet migration visible by stereomicroscopy). Among the various anticoagulants employed, sodium citrate was most suitable for studying platelet migration. Optimal migration occured at 22 degrees to 37 degrees C and pH 7.2 to 7.4. Migration was inhibited by metabolic inhibitors such as iodoacetic acid, sodium fluoride, and 2,4-dinitrophenol, and inhibition was proportional to the dose of the agent added to the incubation medium. Mobility was also inhibited by cytochalasin B, which disrupts cellular microfilaments, at 1 microgram/ml PFP, but not by colchicine, a microtubule inhibitor, even at 40 microgram/ml of PFP. Light and electron microscopy showed that this inhibition was not ascribable to platelet clumping. These observations suggest that platelet mobility is an active process. The possible significance of platelet migration in hemostasis is discussed.", "contents": "Factors which influence blood platelet migration. Migration of human blood platelets in vitro was investigated by a modification of the capillary-tube migration chamber technique used to study the migration inhibition factor of macrophages. Platelets were packed in capillary tubes and incubated in autologous platelet-free plasma (PFP). The extent of migration was quantified by planimetry (measurement of the area of platelet migration visible by stereomicroscopy). Among the various anticoagulants employed, sodium citrate was most suitable for studying platelet migration. Optimal migration occured at 22 degrees to 37 degrees C and pH 7.2 to 7.4. Migration was inhibited by metabolic inhibitors such as iodoacetic acid, sodium fluoride, and 2,4-dinitrophenol, and inhibition was proportional to the dose of the agent added to the incubation medium. Mobility was also inhibited by cytochalasin B, which disrupts cellular microfilaments, at 1 microgram/ml PFP, but not by colchicine, a microtubule inhibitor, even at 40 microgram/ml of PFP. Light and electron microscopy showed that this inhibition was not ascribable to platelet clumping. These observations suggest that platelet mobility is an active process. The possible significance of platelet migration in hemostasis is discussed."}
{"id": "PMID:17643", "title": "Intestinal absorption of alpha-tocopherol in the unanesthetized rat. The influence of luminal constituents on the absorptive process.", "content": "3H-alpha-tocopherol intestinal absorption was studied in the unanesthetized rat. The rate of alpha-tocopherol absorption remained linear over a wide range of concentrations (4 nM to 400 micrometer). Increasing the sodium taurocholate concentration in the micellar infusate up to 15 mM did not increase the rate of absorption of the vitamin. Addition of long-chain fatty acids to the micellar infusate decreased the absorption rate of the vitamin (p less than 0.05). The decrease was most significant (p less than 0.01) following the addition of the polyunsaturated linolenic (C18:3) acid. Increasing the hydrogen ion concentration in the perfusate increased the absorption rate of alpha-tocopherol. The present experiments in vivo support the conclusions drawn from in vitro uptake experiments which indicated that alpha-tocopherol is absorbed by a passive diffusion process. These experiments indicate that micellar expansion with polyunsaturated fatty acids interferes with the absorption of alpha-tocopherol and may result in deficiency of the vitamin.", "contents": "Intestinal absorption of alpha-tocopherol in the unanesthetized rat. The influence of luminal constituents on the absorptive process. 3H-alpha-tocopherol intestinal absorption was studied in the unanesthetized rat. The rate of alpha-tocopherol absorption remained linear over a wide range of concentrations (4 nM to 400 micrometer). Increasing the sodium taurocholate concentration in the micellar infusate up to 15 mM did not increase the rate of absorption of the vitamin. Addition of long-chain fatty acids to the micellar infusate decreased the absorption rate of the vitamin (p less than 0.05). The decrease was most significant (p less than 0.01) following the addition of the polyunsaturated linolenic (C18:3) acid. Increasing the hydrogen ion concentration in the perfusate increased the absorption rate of alpha-tocopherol. The present experiments in vivo support the conclusions drawn from in vitro uptake experiments which indicated that alpha-tocopherol is absorbed by a passive diffusion process. These experiments indicate that micellar expansion with polyunsaturated fatty acids interferes with the absorption of alpha-tocopherol and may result in deficiency of the vitamin."}
{"id": "PMID:17644", "title": "The defect of uric acid metabolism in Eck-fistula rats.", "content": "Because of the discovery of uric acid urolithiasis in rats after end-to-side portacaval anastomosis (PCA), uric acid metabolism was studied in these animals and in appropriate controls. Hyperuricemia and hyperuricosuria were observed in all experimental rats. The fraction of purine catabolites excreted in the urine as uric acid increased from an average of 4.8% to 15.3%. If 14C-uric specifically labeled at position 6 (6-14C-ua) was infused intravenously and the exhalation of 14CO2 was used to calculate a hepatic uric acid clearance, it decreased from 2.14 to 0.97 ml/min/100 gm despite a normal content of hepatic uricase activity as measured in liver homogenates. The fraction of the filtered amount of uric acid excreted in the urine increased from an average of 11% to 30%. Increased supersaturation of the urine with uric acid after PCA may be expected to contribute to the formation of uric acid urolithiasis. This investigation defines a hepatic and renal functional defect in uric acid metabolism which occurs as a result of the PCA.", "contents": "The defect of uric acid metabolism in Eck-fistula rats. Because of the discovery of uric acid urolithiasis in rats after end-to-side portacaval anastomosis (PCA), uric acid metabolism was studied in these animals and in appropriate controls. Hyperuricemia and hyperuricosuria were observed in all experimental rats. The fraction of purine catabolites excreted in the urine as uric acid increased from an average of 4.8% to 15.3%. If 14C-uric specifically labeled at position 6 (6-14C-ua) was infused intravenously and the exhalation of 14CO2 was used to calculate a hepatic uric acid clearance, it decreased from 2.14 to 0.97 ml/min/100 gm despite a normal content of hepatic uricase activity as measured in liver homogenates. The fraction of the filtered amount of uric acid excreted in the urine increased from an average of 11% to 30%. Increased supersaturation of the urine with uric acid after PCA may be expected to contribute to the formation of uric acid urolithiasis. This investigation defines a hepatic and renal functional defect in uric acid metabolism which occurs as a result of the PCA."}
{"id": "PMID:17647", "title": "Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts.", "content": "BALB/c mice were treated with fractionated high dose (3,400 rads) total lymphoid irradiation (TLI), and given semiallogeneic (BALB/c x C57BL/Ka) or allogeneic (C57BL/Ka) bone marrow and/or skin allografts. TLI alone prolonged the mean survival time (m.s.t.) of C57BL/Ka skin grafts to 49.1 days (control, 10.7 days). Shielding of the thymus during TLI produced only a slight increase in graft survival (m.s.t., 19 days). TLI combined with splenectomy was no more effective than TLI alone. Infusion of 10(7) semiallogeneic or allogeneic bone marrow cells after TLI produced stable chimeras in 7/8 and 8/15 recipients, respectively. Chimeras were specifically tolerant to donor tissues, since C57BL/Ka skin grafts were accepted for more than 250 days, but third-party (C3H/He) skin grafts were rejected rapidly. In addition, chimeric lymphocytes responded to C3H/He and C3H. Q but not to C57BL/Ka cells in the one-way mixed leukocyte reactions. BALB/c C57BL/Ka chimeras showed no clinical evidence of graft vs. host disease. These findings may have application of clinical organ transplantation, since (a) the recipient treatment (TLI) has already been shown to be safe in humans, (b) donors and recipients can be completely allogeneic, and (c) bone marrow and skin graft survival was permanent (greater than 250 days).", "contents": "Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts. BALB/c mice were treated with fractionated high dose (3,400 rads) total lymphoid irradiation (TLI), and given semiallogeneic (BALB/c x C57BL/Ka) or allogeneic (C57BL/Ka) bone marrow and/or skin allografts. TLI alone prolonged the mean survival time (m.s.t.) of C57BL/Ka skin grafts to 49.1 days (control, 10.7 days). Shielding of the thymus during TLI produced only a slight increase in graft survival (m.s.t., 19 days). TLI combined with splenectomy was no more effective than TLI alone. Infusion of 10(7) semiallogeneic or allogeneic bone marrow cells after TLI produced stable chimeras in 7/8 and 8/15 recipients, respectively. Chimeras were specifically tolerant to donor tissues, since C57BL/Ka skin grafts were accepted for more than 250 days, but third-party (C3H/He) skin grafts were rejected rapidly. In addition, chimeric lymphocytes responded to C3H/He and C3H. Q but not to C57BL/Ka cells in the one-way mixed leukocyte reactions. BALB/c C57BL/Ka chimeras showed no clinical evidence of graft vs. host disease. These findings may have application of clinical organ transplantation, since (a) the recipient treatment (TLI) has already been shown to be safe in humans, (b) donors and recipients can be completely allogeneic, and (c) bone marrow and skin graft survival was permanent (greater than 250 days)."}
{"id": "PMID:17648", "title": "The phosphoenol-pyruvate branchpoint in adult Hymenolepis diminuta (Cestoda): a study of pyruvate kinase and phosphoenol-pyruvate carboxykinase.", "content": "The properties of pyruvate kinase (PK) and phosphoenol pyruvate carboxykinase (PEP CK), two enzymes that determine the preferrential accumulation of either succinate or lactate as endproducts of carbohydrate metabolism, are described in adult Hymenolepis diminuta. PK activity at Vmax and Km levels of PEP was unaffected by ATP, alanine, FDP4, OR H+ ions, but was inhibited by 50% at 6.3 mM L-lactate and 30 mM HCO3. The addition of 30 mM HCO3 increased the Km(PEP) by 6-fold but did not alter the Vmax. The inhibition of PK by HCO3 cannot be explained entirely by an effect of ionic strength, but probably represents a specific modulator-enzyme interaction. Under similar conditions PEP CK was maximally activated. Although L-lactate inhibited PEP CK (Ki(lac) = 1.8 mM), this effector may play a minor role in regulation of PEP flux. These results implicate the poise of the HCO3-:CO2 system as a major determiner  of endproduct accumulation in H. diminuta.", "contents": "The phosphoenol-pyruvate branchpoint in adult Hymenolepis diminuta (Cestoda): a study of pyruvate kinase and phosphoenol-pyruvate carboxykinase. The properties of pyruvate kinase (PK) and phosphoenol pyruvate carboxykinase (PEP CK), two enzymes that determine the preferrential accumulation of either succinate or lactate as endproducts of carbohydrate metabolism, are described in adult Hymenolepis diminuta. PK activity at Vmax and Km levels of PEP was unaffected by ATP, alanine, FDP4, OR H+ ions, but was inhibited by 50% at 6.3 mM L-lactate and 30 mM HCO3. The addition of 30 mM HCO3 increased the Km(PEP) by 6-fold but did not alter the Vmax. The inhibition of PK by HCO3 cannot be explained entirely by an effect of ionic strength, but probably represents a specific modulator-enzyme interaction. Under similar conditions PEP CK was maximally activated. Although L-lactate inhibited PEP CK (Ki(lac) = 1.8 mM), this effector may play a minor role in regulation of PEP flux. These results implicate the poise of the HCO3-:CO2 system as a major determiner  of endproduct accumulation in H. diminuta."}
{"id": "PMID:17650", "title": "The biosynthesis of a choline nucleotide by a cell-free extract from Streptococcus pneumoniae.", "content": "Choline, a component of the wall teichoic acid of Streptococcus pneumoniae, was converted to cytidine diphosphocholine via choline phosphate by enzymes which were identified in cell-free extracts of the pneumococcus. The first enzyme, choline kinase, was investigated in some detail. It appeared to have a pH optimum of 7.3 to 7.4 and was stimulated by Mg2+. Kinetic studies gave an apparent Michaelis constant (Km) for ATP of I mM, and for choline of 0.19 mM, with Vmax values of 3 nmol min-1 (mg protein)-1 and 0.5 nmol min-1 (mg protein)-1 respectively. The second enzyme, CDPcholine pyrophosphorylase was specific for CTP and had a requirement for Mg2+ with an optimum at 7 mM.", "contents": "The biosynthesis of a choline nucleotide by a cell-free extract from Streptococcus pneumoniae. Choline, a component of the wall teichoic acid of Streptococcus pneumoniae, was converted to cytidine diphosphocholine via choline phosphate by enzymes which were identified in cell-free extracts of the pneumococcus. The first enzyme, choline kinase, was investigated in some detail. It appeared to have a pH optimum of 7.3 to 7.4 and was stimulated by Mg2+. Kinetic studies gave an apparent Michaelis constant (Km) for ATP of I mM, and for choline of 0.19 mM, with Vmax values of 3 nmol min-1 (mg protein)-1 and 0.5 nmol min-1 (mg protein)-1 respectively. The second enzyme, CDPcholine pyrophosphorylase was specific for CTP and had a requirement for Mg2+ with an optimum at 7 mM."}
{"id": "PMID:17659", "title": "Childhood pheochromocytoma: treatment with alpha methyl tyrosine for resistant hypertension.", "content": "A 12-year-old boy with a norepinephrine-secreting pheochromocytoma that caused hypertension resistant to oral alpha adrenergic blockade is reported. Resistance to alpha adrenergic blocking agents developed when the patient's daily propranolol dosage was lowered from 10 to 1 mg/kg. Subsequently, alpha methyl tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, controlled the patient's blood pressure and was associated with reduction in total urinary catecholamine excretion. Norepinephrine content of the tumor and uninvolved adrenal gland removal at surgery was reduced. These findings confirm that alpha methyl tyrosine inhibited in vivo synthesis of catecholamines.", "contents": "Childhood pheochromocytoma: treatment with alpha methyl tyrosine for resistant hypertension. A 12-year-old boy with a norepinephrine-secreting pheochromocytoma that caused hypertension resistant to oral alpha adrenergic blockade is reported. Resistance to alpha adrenergic blocking agents developed when the patient's daily propranolol dosage was lowered from 10 to 1 mg/kg. Subsequently, alpha methyl tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, controlled the patient's blood pressure and was associated with reduction in total urinary catecholamine excretion. Norepinephrine content of the tumor and uninvolved adrenal gland removal at surgery was reduced. These findings confirm that alpha methyl tyrosine inhibited in vivo synthesis of catecholamines."}
{"id": "PMID:17661", "title": "A syndrome of childhood polyarteritis.", "content": "In this report the clinical, laboratory, and histopathologic findings of nine children with polyarteritis are reviewed. All have had evidence of systemic involvement. Eight presented with fever, calf pain, erythematous painful nodules, and elevation of the acute-phase reactants. All were treated with prednisone at a dosage of 2 mg/kg/day. All of the children are alive but have had relapses at least once during the course of tapering the dosage of corticosteroids. Serious complications of disease have included myocardial infarction, hypertension, and impaired renal function.", "contents": "A syndrome of childhood polyarteritis. In this report the clinical, laboratory, and histopathologic findings of nine children with polyarteritis are reviewed. All have had evidence of systemic involvement. Eight presented with fever, calf pain, erythematous painful nodules, and elevation of the acute-phase reactants. All were treated with prednisone at a dosage of 2 mg/kg/day. All of the children are alive but have had relapses at least once during the course of tapering the dosage of corticosteroids. Serious complications of disease have included myocardial infarction, hypertension, and impaired renal function."}
{"id": "PMID:17662", "title": "Necrotizing arteritis in acute poststreptococcal glomerulonephritis: report of a recovered case.", "content": "A patient with biopsy documented acute poststreptococcal glomerulonephritis and arteritis recovered completely with supportive therapy. Illness was preceded by group A streptococcal pharyngitis. At the time of presentation, serum creatinine concentration was 11.5 mg/dl. Serum cryoglobulins containing IgG and C3 were present. The first biopsy, performed during the acute illness, contained glomeruli with typical features of acute PSGN. Medium-sized arteries had extensive necrosis and leukocytic infiltration, and contained IgG, C3, and fibrin. Glomerular filtration rate returned to normal within three weeks; proteinuria cleared by three months, and microscopic hematuria by 11 months. Renal biopsy one year later showed minimal mesangial hypercellularity and no arteritis.", "contents": "Necrotizing arteritis in acute poststreptococcal glomerulonephritis: report of a recovered case. A patient with biopsy documented acute poststreptococcal glomerulonephritis and arteritis recovered completely with supportive therapy. Illness was preceded by group A streptococcal pharyngitis. At the time of presentation, serum creatinine concentration was 11.5 mg/dl. Serum cryoglobulins containing IgG and C3 were present. The first biopsy, performed during the acute illness, contained glomeruli with typical features of acute PSGN. Medium-sized arteries had extensive necrosis and leukocytic infiltration, and contained IgG, C3, and fibrin. Glomerular filtration rate returned to normal within three weeks; proteinuria cleared by three months, and microscopic hematuria by 11 months. Renal biopsy one year later showed minimal mesangial hypercellularity and no arteritis."}
{"id": "PMID:17663", "title": "Studies in acid-base balance. I. Effect of alkali therapy in newborn dogs with mechanically fixed ventilation.", "content": "The effect of rapid or slow infusion of hypertonic sodium bicarbonate on acid-base balance and serum osmolality was studied in 36 acidotic newborn dogs. Respiratory acidosis and hypoxia were produced by mechanically fixed hypoventilation. One group of animals breathed 100% O2 to prevent hypoxemia. Rapid infusion of HCO3- in acidotic and hypoxic animals resulted in only a transient (1 minute) and small (0.05 pH units) elevation of arterial pH followed by a continuous fall, resulting in a lower pH and a worsened metabolic condition than in the nontreated controls. In nonhypoxic acidotic animals, rapid infusion of HCO3- had little effect on arterial pH. PaCO2 increased suddenly by 17 Torr in hypoxic and, by 13 Torr, in nonhypoxic animals. There was a concomitant fall in PaO2 (15 Torr). Serum osmolality rose rapidly after rapid infusion of HCO3-. Rapid infusion of hypertonic bicarbonate into an animal or infant whose ventilation is fixed thus results in a less than predicted elevation of arterial pH. PaCO2 rises, PaO2 falls, and serum osmolality rises. The net result may be a worsening rather than an improvement in the animals' metabolic state.", "contents": "Studies in acid-base balance. I. Effect of alkali therapy in newborn dogs with mechanically fixed ventilation. The effect of rapid or slow infusion of hypertonic sodium bicarbonate on acid-base balance and serum osmolality was studied in 36 acidotic newborn dogs. Respiratory acidosis and hypoxia were produced by mechanically fixed hypoventilation. One group of animals breathed 100% O2 to prevent hypoxemia. Rapid infusion of HCO3- in acidotic and hypoxic animals resulted in only a transient (1 minute) and small (0.05 pH units) elevation of arterial pH followed by a continuous fall, resulting in a lower pH and a worsened metabolic condition than in the nontreated controls. In nonhypoxic acidotic animals, rapid infusion of HCO3- had little effect on arterial pH. PaCO2 increased suddenly by 17 Torr in hypoxic and, by 13 Torr, in nonhypoxic animals. There was a concomitant fall in PaO2 (15 Torr). Serum osmolality rose rapidly after rapid infusion of HCO3-. Rapid infusion of hypertonic bicarbonate into an animal or infant whose ventilation is fixed thus results in a less than predicted elevation of arterial pH. PaCO2 rises, PaO2 falls, and serum osmolality rises. The net result may be a worsening rather than an improvement in the animals' metabolic state."}
{"id": "PMID:17665", "title": "Mullerian inhibiting substance in human testes after birth.", "content": "Tiny testicular biopsies from humans were assayed for Mullerian inhibiting Substances using a graded organ culture technique. Mullerian Inhibiting Substance activity was high during the first year of life, declined during the second year of life, and then disappeared. Mullerian Inhibiting Substance activity is lower in boys with undescended testis than in children with normal or intersex testes at comparable ages under two years. It is possible that Mullerian Inhibiting Substance affects testicular descent as well as causing Mullerian duct regression.", "contents": "Mullerian inhibiting substance in human testes after birth. Tiny testicular biopsies from humans were assayed for Mullerian inhibiting Substances using a graded organ culture technique. Mullerian Inhibiting Substance activity was high during the first year of life, declined during the second year of life, and then disappeared. Mullerian Inhibiting Substance activity is lower in boys with undescended testis than in children with normal or intersex testes at comparable ages under two years. It is possible that Mullerian Inhibiting Substance affects testicular descent as well as causing Mullerian duct regression."}
{"id": "PMID:17667", "title": "Pharmaceutical suspensions: relation between zeta potential, sedimentation volume and suspension stability.", "content": "The effect of added surface-active agents of various ionic types on the sedimentation volume of drug suspensions of betamethasone, griseofulvin, nalidixic acid and thiabendazole has been investigated, and the results correlated with previously measured zeta potentials. Study of the zeta potential/sedimentation volumes versus concentration plots showed that apparently only coagulated, deflocculated or sterically stabilized systems were formed. In most cases the sterically stabilized systems were produced from mixtures of ionic/non-ionic surfactants. These are examples of controlled coagulation, although non-ionic surfactant alone conferred stability against caking. Secondary minimum flocculation was not apparent but this may have been due to the method of examination of suspensions. The work confirmed that the DLVO theory of colloid stability and its modification to include a steric term can be applied to coarse suspension systems.", "contents": "Pharmaceutical suspensions: relation between zeta potential, sedimentation volume and suspension stability. The effect of added surface-active agents of various ionic types on the sedimentation volume of drug suspensions of betamethasone, griseofulvin, nalidixic acid and thiabendazole has been investigated, and the results correlated with previously measured zeta potentials. Study of the zeta potential/sedimentation volumes versus concentration plots showed that apparently only coagulated, deflocculated or sterically stabilized systems were formed. In most cases the sterically stabilized systems were produced from mixtures of ionic/non-ionic surfactants. These are examples of controlled coagulation, although non-ionic surfactant alone conferred stability against caking. Secondary minimum flocculation was not apparent but this may have been due to the method of examination of suspensions. The work confirmed that the DLVO theory of colloid stability and its modification to include a steric term can be applied to coarse suspension systems."}
{"id": "PMID:17668", "title": "The in vitro bioavailability of various drugs formulated as hard gelatin capsules.", "content": "A factorially designed experiment has been carried out to study the influence of various additives on the in vitro release of drug from hard gelatin capsules. Analysis of variance confirms previous findings that, although the main factors of diluent type, diluent concentration, the absence and presence of both magnesium stearate and sodium lauryl sulphate, were highly significant, the existence of interactions between the factors prevented exact quantitative prediction of the influence of each factor. There appears however, to be a strong indication that the in vitro drug release of capsule formulations (y), expressed as the % of the drug content of the capsule which dissolves, can be related to the solubility of the drug (cs) by the expression y = 21-2 log cs + 31.2.", "contents": "The in vitro bioavailability of various drugs formulated as hard gelatin capsules. A factorially designed experiment has been carried out to study the influence of various additives on the in vitro release of drug from hard gelatin capsules. Analysis of variance confirms previous findings that, although the main factors of diluent type, diluent concentration, the absence and presence of both magnesium stearate and sodium lauryl sulphate, were highly significant, the existence of interactions between the factors prevented exact quantitative prediction of the influence of each factor. There appears however, to be a strong indication that the in vitro drug release of capsule formulations (y), expressed as the % of the drug content of the capsule which dissolves, can be related to the solubility of the drug (cs) by the expression y = 21-2 log cs + 31.2."}
{"id": "PMID:17664", "title": "Extraocular muscle transplantation.", "content": "1. The transplantation of extraocular homografts in dogs and humans has been described. 2. The extraocular muscle tissue transplanted remains viable, but loses its characteristics of muscle tissue during the period of the normal healing process following extraocular muscle surgery. 3. Autogenous homograft of extraocular muscle has an advantage over artificial synthetic material with the absence of extrusion and less reaction. 4. This is a clinically usable procedure today, especially in the amblyopic ehe with high deviation to accomplish an additional lengthening of one extraocular muscle, particularly if extraocular muscle surgery has previously been performed.", "contents": "Extraocular muscle transplantation. 1. The transplantation of extraocular homografts in dogs and humans has been described. 2. The extraocular muscle tissue transplanted remains viable, but loses its characteristics of muscle tissue during the period of the normal healing process following extraocular muscle surgery. 3. Autogenous homograft of extraocular muscle has an advantage over artificial synthetic material with the absence of extrusion and less reaction. 4. This is a clinically usable procedure today, especially in the amblyopic ehe with high deviation to accomplish an additional lengthening of one extraocular muscle, particularly if extraocular muscle surgery has previously been performed."}
{"id": "PMID:17669", "title": "Phase equilibria and stability characteristics of chlorpropamide-urea solid dispersions.", "content": "Physical mixtures and melts of various compositions of chlorpropamide and urea have been prepared. The phase diagrams and the effects of ageing of the systems have been measured by differential scanning calorimetry. The eutectic composition was found to contain 89% w/w chlorpropamide. Greater concentrations of chlorpropamide produced solid solutions of urea in chlorpropamide, whereas solid solution formation did not occur at compositions less than 89%. Melts in the range 50-100% chlorpropamide, which included the eutectic, existed as glass solids. The effect of ageing produced generally an increase in the liquidus peak temperature which was considered to be due to a gradual increase in crystal size.", "contents": "Phase equilibria and stability characteristics of chlorpropamide-urea solid dispersions. Physical mixtures and melts of various compositions of chlorpropamide and urea have been prepared. The phase diagrams and the effects of ageing of the systems have been measured by differential scanning calorimetry. The eutectic composition was found to contain 89% w/w chlorpropamide. Greater concentrations of chlorpropamide produced solid solutions of urea in chlorpropamide, whereas solid solution formation did not occur at compositions less than 89%. Melts in the range 50-100% chlorpropamide, which included the eutectic, existed as glass solids. The effect of ageing produced generally an increase in the liquidus peak temperature which was considered to be due to a gradual increase in crystal size."}
{"id": "PMID:17670", "title": "Derivatization to stabilize some aliphatic primary hydroxylamines for g.l.c. analysis.", "content": "By appropriate choice of trimethylsilylating and trifluoroacetylating reagents and organic solvents for extraction, stable derivative of aliphatic primary hydroxylamines metabolites, N-hydroxyphentermine, N-hydroxychlorphentermine, N-hydroxymexiletene, N-hydroxyphenethylamine, N-hydroxyamphetamine, and N-hydroxy-3,4-dimethoxyamphetamine, were obtained and examined by g.l.c. analysis without decomposition and without interference from the parent drug or other metabolic products.", "contents": "Derivatization to stabilize some aliphatic primary hydroxylamines for g.l.c. analysis. By appropriate choice of trimethylsilylating and trifluoroacetylating reagents and organic solvents for extraction, stable derivative of aliphatic primary hydroxylamines metabolites, N-hydroxyphentermine, N-hydroxychlorphentermine, N-hydroxymexiletene, N-hydroxyphenethylamine, N-hydroxyamphetamine, and N-hydroxy-3,4-dimethoxyamphetamine, were obtained and examined by g.l.c. analysis without decomposition and without interference from the parent drug or other metabolic products."}
{"id": "PMID:17672", "title": "Carrageenan and thrombin trigger prostaglandin synthetase-independent aggregation of rabbit platelets: inhibition by phospholipase A2 inhibitors.", "content": "Acetylsalicylic acid, salicylic acid and indomethacin were equally effective in inhibiting aggregation of plasma-free rabbit platelets induced by carrageenan and by thrombin. In contrast, only acetylsalicylic acid and indomethacin suppressed the accompanying formation of prostaglandin-like activities. Blockade of aggregation required the presence of the inhibitors in the platelet preparation, whereas blockade of prostaglandin synthetase remained even when the inhibitors were washed out. Prostaglandin synthetase-derived  products appear not to be involved in the development of aggregation by carrageenan or by thrombin. Such aggregation was inhibited by two phospholipase A2 inhibitors, bromophenacyl bromide and mepacrine. It is suggested that carrageenan and thrombin-induced aggregation are mediated by non-prostaglandin, phospholipase A2-derived products.", "contents": "Carrageenan and thrombin trigger prostaglandin synthetase-independent aggregation of rabbit platelets: inhibition by phospholipase A2 inhibitors. Acetylsalicylic acid, salicylic acid and indomethacin were equally effective in inhibiting aggregation of plasma-free rabbit platelets induced by carrageenan and by thrombin. In contrast, only acetylsalicylic acid and indomethacin suppressed the accompanying formation of prostaglandin-like activities. Blockade of aggregation required the presence of the inhibitors in the platelet preparation, whereas blockade of prostaglandin synthetase remained even when the inhibitors were washed out. Prostaglandin synthetase-derived  products appear not to be involved in the development of aggregation by carrageenan or by thrombin. Such aggregation was inhibited by two phospholipase A2 inhibitors, bromophenacyl bromide and mepacrine. It is suggested that carrageenan and thrombin-induced aggregation are mediated by non-prostaglandin, phospholipase A2-derived products."}
{"id": "PMID:17673", "title": "The interaction between clonidine and various neuroleptic agents and some benzodiazepine tranquillizers.", "content": "The central hypotensive action of clonidine, infused into the vertebral artery of chloralose-anaesthetized cats was antagonized by several phenothiazine-neuroleptics (chlorpromazine, promazine, promethazine, thiethylperazine, thioridazine), by chlorprothixene and to a limited extent by haloperidol administered via the same route. Pimozide and some benzodiazepines (chlordiazepoxide, diazepam and flurazepam) hardly influenced the central hypotensive response to clonidine. The antagonism between clonidine and the psychotropic drugs is probably associated with central alpha-adrenoceptors, clonidine being the agonist and the neuroleptic agents the antagonists at these receptors. Virtually the same type of antagonism was observed in conscious, spontaneously hypertensive rats where both clonidine and the neuroleptic drugs were injected intravenously. The phenothiazines and also piperoxane effectively diminished the centrally induced hypotensive response to clonidine, whereas the initial pressor effect to clonidine was not reduced.", "contents": "The interaction between clonidine and various neuroleptic agents and some benzodiazepine tranquillizers. The central hypotensive action of clonidine, infused into the vertebral artery of chloralose-anaesthetized cats was antagonized by several phenothiazine-neuroleptics (chlorpromazine, promazine, promethazine, thiethylperazine, thioridazine), by chlorprothixene and to a limited extent by haloperidol administered via the same route. Pimozide and some benzodiazepines (chlordiazepoxide, diazepam and flurazepam) hardly influenced the central hypotensive response to clonidine. The antagonism between clonidine and the psychotropic drugs is probably associated with central alpha-adrenoceptors, clonidine being the agonist and the neuroleptic agents the antagonists at these receptors. Virtually the same type of antagonism was observed in conscious, spontaneously hypertensive rats where both clonidine and the neuroleptic drugs were injected intravenously. The phenothiazines and also piperoxane effectively diminished the centrally induced hypotensive response to clonidine, whereas the initial pressor effect to clonidine was not reduced."}
{"id": "PMID:17687", "title": "The enkephalins and opiates: structure-activity relations.", "content": "The X-ray structures of 9 \"opiate\" drugs which exhibit a range of pharmacological activity have been examined in detail leading to the theory that one of the reasons why the enkephalins and related peptides possess morphine-like activity is because they have a tyrosine, and hence a \"tyramine\", residue at the amino terminal position. This residue or a conformationally similar moiety, can be shown to be present in many opiates and analogues.", "contents": "The enkephalins and opiates: structure-activity relations. The X-ray structures of 9 \"opiate\" drugs which exhibit a range of pharmacological activity have been examined in detail leading to the theory that one of the reasons why the enkephalins and related peptides possess morphine-like activity is because they have a tyrosine, and hence a \"tyramine\", residue at the amino terminal position. This residue or a conformationally similar moiety, can be shown to be present in many opiates and analogues."}
{"id": "PMID:17688", "title": "Stereoselective drug distribution and anticoagulant potency of the enantiomers of phenprocoumon in rats.", "content": "The elimination, distribution and anticoagulant activity of S(-)-, R(+)-, and R,S(+/-)- phenoprocoumon were determined in male Wistar-Lewis rats after intravenous injection of a single dose of 0.6 mg kg-1. From the plasma concentrations which elicited the same anticoagulant effect, S(-)-phenprocoumon was 4 to 5 times more potent than R(+)-phenprocouman. The potency of the racemate was between those of the enantiomers. The mean biologic half-life of the S(-)-enantiomer was shorter (12-5 h) than that of R(+)-phenprocoumon (17-8 h). No differences were observed in the apparent volume of distribution. However, the mean liver:plasma concentration ratio was higher for the S(-)-(6-9) than for the R(+)-enantiomer (5-2). At a total concentration of 16-8 microgram ml-1 the percentage of unbound drug in rat serum was significantly higher for the S(-)- (1-13%) than that for the R(+)-enantiomer (0.76%). Values obtained for the racemate were always between those of the enantiomers. It is concluded that stereoselective differences in the distribution between plasma and liver, and consequently in the rate of elimination are most likely due to stereoselective differences in serum protein binding. The greater anticoagulant potency of the S(-)- over the R(+)-enantiomer, cannot be explained primarily by the observed pharmacokinetic differences.", "contents": "Stereoselective drug distribution and anticoagulant potency of the enantiomers of phenprocoumon in rats. The elimination, distribution and anticoagulant activity of S(-)-, R(+)-, and R,S(+/-)- phenoprocoumon were determined in male Wistar-Lewis rats after intravenous injection of a single dose of 0.6 mg kg-1. From the plasma concentrations which elicited the same anticoagulant effect, S(-)-phenprocoumon was 4 to 5 times more potent than R(+)-phenprocouman. The potency of the racemate was between those of the enantiomers. The mean biologic half-life of the S(-)-enantiomer was shorter (12-5 h) than that of R(+)-phenprocoumon (17-8 h). No differences were observed in the apparent volume of distribution. However, the mean liver:plasma concentration ratio was higher for the S(-)-(6-9) than for the R(+)-enantiomer (5-2). At a total concentration of 16-8 microgram ml-1 the percentage of unbound drug in rat serum was significantly higher for the S(-)- (1-13%) than that for the R(+)-enantiomer (0.76%). Values obtained for the racemate were always between those of the enantiomers. It is concluded that stereoselective differences in the distribution between plasma and liver, and consequently in the rate of elimination are most likely due to stereoselective differences in serum protein binding. The greater anticoagulant potency of the S(-)- over the R(+)-enantiomer, cannot be explained primarily by the observed pharmacokinetic differences."}
{"id": "PMID:17689", "title": "The effects of etilefrine on blood vessels in the rat tail.", "content": "Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreagment with noradrenaline and cocaine, and totally abolished by the alpha-receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension.", "contents": "The effects of etilefrine on blood vessels in the rat tail. Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreagment with noradrenaline and cocaine, and totally abolished by the alpha-receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension."}
{"id": "PMID:17690", "title": "The effects of prostaglandins E1, E2, F1alpha and  F2alpha on guinea-pig ileal and colonic peristalis.", "content": "Prostaglandins (PGE1, E2, F1alpha and F2alpha) have been tested on the peristaltic reflex in isolated segments of guinea-pig ileum and colon using simultaneous recordings of fluid propulsion and longitudinal and circular muscle activity. Propulsion and circular muscle peristaltic activity were increased by serosally applied PGF compounds in the ileum and PGE or PGF compounds in the colon following initial contraction of the longitudinal muscle. This is consistent with a role for prostaglandins in peristalsis. Mucosally applied PGF compounds has no significant effect.", "contents": "The effects of prostaglandins E1, E2, F1alpha and  F2alpha on guinea-pig ileal and colonic peristalis. Prostaglandins (PGE1, E2, F1alpha and F2alpha) have been tested on the peristaltic reflex in isolated segments of guinea-pig ileum and colon using simultaneous recordings of fluid propulsion and longitudinal and circular muscle activity. Propulsion and circular muscle peristaltic activity were increased by serosally applied PGF compounds in the ileum and PGE or PGF compounds in the colon following initial contraction of the longitudinal muscle. This is consistent with a role for prostaglandins in peristalsis. Mucosally applied PGF compounds has no significant effect."}
{"id": "PMID:17691", "title": "The identification and analysis of mexiletine and its metabolic products in man.", "content": "Sensitive and specific gas-liquid chromatographic methods were developed for the analysis of mexiletine and its metabolites in urine of man. The identity of the g.l.c. peaks was established by mass-spectrometry. The hydroxylamine (Va) was qualitatively identified and determined quantitatively after conversion to the more stable oxime (Vb). Selective extraction procedures, t.l.c. and derivatization with hexamethyldisilazane (HMDS) and trifluoroacetic anhydride (TFA) were used in the qualitative identification of the major metabolites (VI-IX), particularly in distinguishing the basic products VI and VII from their corresponding alcoholic products VIII and IX. The limit of detection of the g.l.c. method was 6 to 12 ng ml-1 for compounds I-IV, and 40 to 50 ng ml-1 for compounds Vb-IX.", "contents": "The identification and analysis of mexiletine and its metabolic products in man. Sensitive and specific gas-liquid chromatographic methods were developed for the analysis of mexiletine and its metabolites in urine of man. The identity of the g.l.c. peaks was established by mass-spectrometry. The hydroxylamine (Va) was qualitatively identified and determined quantitatively after conversion to the more stable oxime (Vb). Selective extraction procedures, t.l.c. and derivatization with hexamethyldisilazane (HMDS) and trifluoroacetic anhydride (TFA) were used in the qualitative identification of the major metabolites (VI-IX), particularly in distinguishing the basic products VI and VII from their corresponding alcoholic products VIII and IX. The limit of detection of the g.l.c. method was 6 to 12 ng ml-1 for compounds I-IV, and 40 to 50 ng ml-1 for compounds Vb-IX."}
{"id": "PMID:17692", "title": "The decomposition of acidic and neutral cannabinoids in organic solvents.", "content": "High-pressure liquid chromatography was used to study (a) the relative efficiencies of methanol, chloroform, light petroleum (B.P. 40-60 degrees) and methanol-chloroform (9:1) for extracting neutral and acidic cannabinoids from cannabis resin; (b) the decomposition patterns of the resulting solutions under various storage conditions, and (c) the cannabinoid profile of a cross section through a block of cannabis resin. The results show that (a) methanol is the most effective extracting solvent of those tested; (b) acidic cannabinoids in solution decompose in darkness by varying amounts depending on the temperature, solvent, storage time and particular cannabinoid; (c) neutral cannabinoids in solution are relatively stable in darkness; (d) daylight causes appreciable decomposition of both acidic and neutral cannabinoids in solution, (e) the cannabinoid profile of a resin is complex with lower levels of acidic material in the outer layers.", "contents": "The decomposition of acidic and neutral cannabinoids in organic solvents. High-pressure liquid chromatography was used to study (a) the relative efficiencies of methanol, chloroform, light petroleum (B.P. 40-60 degrees) and methanol-chloroform (9:1) for extracting neutral and acidic cannabinoids from cannabis resin; (b) the decomposition patterns of the resulting solutions under various storage conditions, and (c) the cannabinoid profile of a cross section through a block of cannabis resin. The results show that (a) methanol is the most effective extracting solvent of those tested; (b) acidic cannabinoids in solution decompose in darkness by varying amounts depending on the temperature, solvent, storage time and particular cannabinoid; (c) neutral cannabinoids in solution are relatively stable in darkness; (d) daylight causes appreciable decomposition of both acidic and neutral cannabinoids in solution, (e) the cannabinoid profile of a resin is complex with lower levels of acidic material in the outer layers."}
{"id": "PMID:17693", "title": "Application of orthogonal functions to the spectrophotometric determination of phenytoin in pharmaceutical preparations.", "content": "A simple ultraviolet spectrophotometric method for the determination of phenytoin in pharmaceutical preparations has been developed. The mean was 100.9% (6 determinations) and the coefficient of variation was 1.2%. The method was applied successfully to the determination of phenytoin in capsules and suspensions.", "contents": "Application of orthogonal functions to the spectrophotometric determination of phenytoin in pharmaceutical preparations. A simple ultraviolet spectrophotometric method for the determination of phenytoin in pharmaceutical preparations has been developed. The mean was 100.9% (6 determinations) and the coefficient of variation was 1.2%. The method was applied successfully to the determination of phenytoin in capsules and suspensions."}
{"id": "PMID:17694", "title": "The influence of additives on the presentation of a drug in hard gelatin capsules.", "content": "The influence of the concentration of lactose, magnesium stearate and sodium lauryl sulphate in the in vitro dissolution and the drug content of hard gelatin capsules filled under conditions which result in  a maximum tapped bulk density, has been evaluated by a factorially-designed experiment. The 3 factors have a significant effect on both drug release and capsule filling. Interactions between the 3 factors, however, limit the exact quantification of the magnitude of their influence by a simple linear model. A quadratic relation, when only 2 factors are considered, can be used to provide a prediction of the influence of these factors. The relations between 2 factors are demonstrated as contours of equal in vitro drug release and equal drug content of capsule, at constant concentrations of the third factor. The contours show the important influence of lactose concentration  drug release and capsule filling, and the large changes in response which can occur by the addition of a third factor. They also provide a clear guide to the formulation of hard gelatin capsules.", "contents": "The influence of additives on the presentation of a drug in hard gelatin capsules. The influence of the concentration of lactose, magnesium stearate and sodium lauryl sulphate in the in vitro dissolution and the drug content of hard gelatin capsules filled under conditions which result in  a maximum tapped bulk density, has been evaluated by a factorially-designed experiment. The 3 factors have a significant effect on both drug release and capsule filling. Interactions between the 3 factors, however, limit the exact quantification of the magnitude of their influence by a simple linear model. A quadratic relation, when only 2 factors are considered, can be used to provide a prediction of the influence of these factors. The relations between 2 factors are demonstrated as contours of equal in vitro drug release and equal drug content of capsule, at constant concentrations of the third factor. The contours show the important influence of lactose concentration  drug release and capsule filling, and the large changes in response which can occur by the addition of a third factor. They also provide a clear guide to the formulation of hard gelatin capsules."}
{"id": "PMID:17695", "title": "The distribution of components in the different size fractions of granules prepared from binary mixtures.", "content": "Boric acid, sulphanilamide and citric acid have been mixed separately with lactose and then granulated by massing and screening. The granules have been fractionated by sieving and each fraction has been analysed for lactose content. The effect of premixing time, massing time, binder volume and ratio of components on the distribution of lactose between size fractions of granules prepared from lactose: boric acid mixtures has been investigated. Uneven distribution of lactose has been found for all blends examined. There is a premixing time and massing time that gives the optimum distribution of lactose for any given blend and binder volume. Increased binder volume in some cases improves granule uniformity. The proportion of lactose in the blend has a major effect on the distribution of this component in the granules, as does the particle size of the lactose. Granules prepared from blends of lactose with sulphanilamide and with citric acid were also examined for lactose distribution.", "contents": "The distribution of components in the different size fractions of granules prepared from binary mixtures. Boric acid, sulphanilamide and citric acid have been mixed separately with lactose and then granulated by massing and screening. The granules have been fractionated by sieving and each fraction has been analysed for lactose content. The effect of premixing time, massing time, binder volume and ratio of components on the distribution of lactose between size fractions of granules prepared from lactose: boric acid mixtures has been investigated. Uneven distribution of lactose has been found for all blends examined. There is a premixing time and massing time that gives the optimum distribution of lactose for any given blend and binder volume. Increased binder volume in some cases improves granule uniformity. The proportion of lactose in the blend has a major effect on the distribution of this component in the granules, as does the particle size of the lactose. Granules prepared from blends of lactose with sulphanilamide and with citric acid were also examined for lactose distribution."}
{"id": "PMID:17708", "title": "Desensitization to portrayals of real-life aggression as a function of exposure to television violence.", "content": "In two separate experiments, the hypothesis that exposure to violence in the context of television drama decreases subjects' emotional responsivity to portrayals of real-life aggression was tested. Subjects were shown either an excerpt from a violent police drama or a segment of an exciting but nonviolent volley-ball game before watching a videotaped scene of real aggression. Emotionality was measured by changes in skin resistance which was measured continuously throughout the session. In Experiment 1, subjects were 8- to 10-year-old children and the real aggression was a film of an argument and fight between two preschoolers. In Experiment 2, college students participated and reactions to real aggression were measured while subjects watched scenes from news films of the riots at the 1968 Democratic National Convention. With the exception of adult females, subjects who previously had viewed the aggression drama were less aroused by the scenes of real aggression than were subjects who had seen the control film. Further support for the hypothesis was provided by the finding that for most groups of subjects, the amount of television violence normally viewed was negatively related to responsivity while viewing aggression.", "contents": "Desensitization to portrayals of real-life aggression as a function of exposure to television violence. In two separate experiments, the hypothesis that exposure to violence in the context of television drama decreases subjects' emotional responsivity to portrayals of real-life aggression was tested. Subjects were shown either an excerpt from a violent police drama or a segment of an exciting but nonviolent volley-ball game before watching a videotaped scene of real aggression. Emotionality was measured by changes in skin resistance which was measured continuously throughout the session. In Experiment 1, subjects were 8- to 10-year-old children and the real aggression was a film of an argument and fight between two preschoolers. In Experiment 2, college students participated and reactions to real aggression were measured while subjects watched scenes from news films of the riots at the 1968 Democratic National Convention. With the exception of adult females, subjects who previously had viewed the aggression drama were less aroused by the scenes of real aggression than were subjects who had seen the control film. Further support for the hypothesis was provided by the finding that for most groups of subjects, the amount of television violence normally viewed was negatively related to responsivity while viewing aggression."}
{"id": "PMID:17710", "title": "Determination of aqueous solubility and pKa values of estrogens.", "content": "Reported estrone pKa and solubility data show wide variation. Improved experimental procedures were designed and used to obtain reproducible results. The pKa values for several estrogens and related compounds also were determined to assess the effects of structural differences on ionization. No evidence was obtained for long-range D to A ring electronic transmission affecting pKa. Significant differences in pKa values resulted only when conjugated unsaturation was added into the B ring of estrone or estradiol. The aqueous solubilities of estrone and 17alpha-estradiol were 0.8 and 3.9 microgram/ml, respectively, at 25degrees.", "contents": "Determination of aqueous solubility and pKa values of estrogens. Reported estrone pKa and solubility data show wide variation. Improved experimental procedures were designed and used to obtain reproducible results. The pKa values for several estrogens and related compounds also were determined to assess the effects of structural differences on ionization. No evidence was obtained for long-range D to A ring electronic transmission affecting pKa. Significant differences in pKa values resulted only when conjugated unsaturation was added into the B ring of estrone or estradiol. The aqueous solubilities of estrone and 17alpha-estradiol were 0.8 and 3.9 microgram/ml, respectively, at 25degrees."}
{"id": "PMID:17711", "title": "Acetylacroninium salts as soluble prodrugs of the antineoplastic agent acronine.", "content": "The low aqueous solubility of acronine (approximately 2 mg/liter) has been overcome by identification of quaternary prodrug salts exhibiting apparent molar solubilities two to five orders of magnitude greater than acronine. The synthesis and kinetics of hydrolysis of the various prodrug acetylacroninium salts were studied, and the half-life for hydrolysis under conditions approximating the in vivo situation was estimated to be about 5 min. Such rapid reversion, together with the greatly increased solubility, appears to qualify the prodrug for intravenous use.", "contents": "Acetylacroninium salts as soluble prodrugs of the antineoplastic agent acronine. The low aqueous solubility of acronine (approximately 2 mg/liter) has been overcome by identification of quaternary prodrug salts exhibiting apparent molar solubilities two to five orders of magnitude greater than acronine. The synthesis and kinetics of hydrolysis of the various prodrug acetylacroninium salts were studied, and the half-life for hydrolysis under conditions approximating the in vivo situation was estimated to be about 5 min. Such rapid reversion, together with the greatly increased solubility, appears to qualify the prodrug for intravenous use."}
{"id": "PMID:17712", "title": "Microencapsulation of phenobarbital by spray polycondensation.", "content": "A new method for the microencapsulation of solids is described. It is based on the polycondensation of amphiphilic and, thus, tensioactive precondensates on a melamine-formaldehyde base on the surface of suspended particles during spray drying. A film-forming agent, preferably one that reacts chemically with the resin, is indispensable for spray drying and also for the formation of an efficient membrane around the drug particles. The resulting microcapsules are essentially spherical and have, after appropriate curing, a sustained-release effect in vitro. The factors that most influence the formation and properties of the microcapsules are the composition (qualitative and quantitative), pH, and viscosity of the suspension.", "contents": "Microencapsulation of phenobarbital by spray polycondensation. A new method for the microencapsulation of solids is described. It is based on the polycondensation of amphiphilic and, thus, tensioactive precondensates on a melamine-formaldehyde base on the surface of suspended particles during spray drying. A film-forming agent, preferably one that reacts chemically with the resin, is indispensable for spray drying and also for the formation of an efficient membrane around the drug particles. The resulting microcapsules are essentially spherical and have, after appropriate curing, a sustained-release effect in vitro. The factors that most influence the formation and properties of the microcapsules are the composition (qualitative and quantitative), pH, and viscosity of the suspension."}
{"id": "PMID:17713", "title": "Quantitative analysis of degradation products in pilocarpine hydrochloride ophthalmic formulations.", "content": "The presence of isopilocarpine, an epimer of pilocarpine, and of pilocarpinic acid, a hydrolytic degradation product of pilocarpine, was established and all three substances were assayed in various commercial ophthalmic formulations of pilocarpine hydrochloride by 13C-Fourier transform spectroscopy. Assay was based upon integrated intensities of selected resonances from any formulation calibrated against the intensity of tetramethylammonium bromide, used as a common external reference. The normalized intensities were then related to those of a reference solution of pilocarpine hydrochloride, thereby eliminating any factor arising from variability of 13C-relaxation times. The 13C-resonance for the N-methyl group, being common to all products, provides a convenient basis for the assay of the total alkaloid content whereas the C-8 resonances are best suited for assaying residual pilocarpine and its degradation products. This procedure, estimated as accurate to +/- 5%, constitutes the first comprehensive analytical method to differentiate between pilocarpine and its degradation products.", "contents": "Quantitative analysis of degradation products in pilocarpine hydrochloride ophthalmic formulations. The presence of isopilocarpine, an epimer of pilocarpine, and of pilocarpinic acid, a hydrolytic degradation product of pilocarpine, was established and all three substances were assayed in various commercial ophthalmic formulations of pilocarpine hydrochloride by 13C-Fourier transform spectroscopy. Assay was based upon integrated intensities of selected resonances from any formulation calibrated against the intensity of tetramethylammonium bromide, used as a common external reference. The normalized intensities were then related to those of a reference solution of pilocarpine hydrochloride, thereby eliminating any factor arising from variability of 13C-relaxation times. The 13C-resonance for the N-methyl group, being common to all products, provides a convenient basis for the assay of the total alkaloid content whereas the C-8 resonances are best suited for assaying residual pilocarpine and its degradation products. This procedure, estimated as accurate to +/- 5%, constitutes the first comprehensive analytical method to differentiate between pilocarpine and its degradation products."}
{"id": "PMID:17714", "title": "Determination of meclizine hydrochloride by ion-pair extraction with methyl orange.", "content": "A method, based on ion-pair extraction, is described for the quantification of meclizine hydrochloride in various pharmaceutical dosage forms, for content uniformity determination, and for concentration monitoring in dissolution and bioavailability studies. Methyl orange, dissolved in pH 2.8 MacIlvaine buffer, gave excellent recovery of meclizine after its isolation from aqueous solutions of gelatin, urine, and blood serum. The chloroform-extracted molecular species appeared to be a 1:1  ion-pair. Beer's law was obeyed for a wide concentration range. Because the extracted species seemed well defined and stable and since a surface or an interphase adsorption phenomenon was not a problem, the reported method is considered sensitive, accurate, precise, rapid, and simple.", "contents": "Determination of meclizine hydrochloride by ion-pair extraction with methyl orange. A method, based on ion-pair extraction, is described for the quantification of meclizine hydrochloride in various pharmaceutical dosage forms, for content uniformity determination, and for concentration monitoring in dissolution and bioavailability studies. Methyl orange, dissolved in pH 2.8 MacIlvaine buffer, gave excellent recovery of meclizine after its isolation from aqueous solutions of gelatin, urine, and blood serum. The chloroform-extracted molecular species appeared to be a 1:1  ion-pair. Beer's law was obeyed for a wide concentration range. Because the extracted species seemed well defined and stable and since a surface or an interphase adsorption phenomenon was not a problem, the reported method is considered sensitive, accurate, precise, rapid, and simple."}
{"id": "PMID:17715", "title": "Recording pH method of characterizing composition and monitoring dissolution profile of an anhydride-acid copolymer and its salt derivatives.", "content": "A sensitive potentiometric monitoring method was developed that permits the continuous measurement of the disolution profiles of methyl vinyl ether-maleic anhydride-acid copolymers and salt derivatives. Three distinct rate periods were observed in the dissolution rate of the anhydride copolymer, expressed as percent anhydride dissolved, was independent of sample weight over the weight range studied. The acid form of the copolymer showed only one dissolution rate period, with dissolution being very rapid. The rapid initial pH decrease observed during the first stage of dissolution for a series of anhydride-acid copolymer powder samples correlated closely with the anhydride-acid ratio, permitting chemical characterization of the copolymer functionality simultaneously with the analysis of dissolution profiles. Similarly, the extent of copolymer alkaline salt conversion was inversely proportional to the initial maximum pH increase observed during the first stage of dissolution of these salts. Mechanisms of dissolution of copolymer powder materials are discussed and compared to the dissolution of compressed disks and films reported previously.", "contents": "Recording pH method of characterizing composition and monitoring dissolution profile of an anhydride-acid copolymer and its salt derivatives. A sensitive potentiometric monitoring method was developed that permits the continuous measurement of the disolution profiles of methyl vinyl ether-maleic anhydride-acid copolymers and salt derivatives. Three distinct rate periods were observed in the dissolution rate of the anhydride copolymer, expressed as percent anhydride dissolved, was independent of sample weight over the weight range studied. The acid form of the copolymer showed only one dissolution rate period, with dissolution being very rapid. The rapid initial pH decrease observed during the first stage of dissolution for a series of anhydride-acid copolymer powder samples correlated closely with the anhydride-acid ratio, permitting chemical characterization of the copolymer functionality simultaneously with the analysis of dissolution profiles. Similarly, the extent of copolymer alkaline salt conversion was inversely proportional to the initial maximum pH increase observed during the first stage of dissolution of these salts. Mechanisms of dissolution of copolymer powder materials are discussed and compared to the dissolution of compressed disks and films reported previously."}
{"id": "PMID:17716", "title": "Systems approach to vaginal delivery of drugs IV: methodology for determination of membrane surface pH.", "content": "A physical model including a diffusional layer in series with the membrane was developed for studying the possible differences between the pH at the membrane surface and that in the bulk solution. Both the membrane-secreted substances (acids and bases) and buffer constituents in the bulk solutions are assumed to contribute to the surface pH. Equations derived for this situation, together with experimental determinations of the acidic dissociation constant of the secreted material, the total secretion flux, the flux of total secreted acidic species, and the diffusion layer thickness, allow estimates to be made of the pH at the membrane surface. With the rabbit vagina, the membrane surface pH was close to that of the bulk solution in most cases. These results were supported by the fact that the absorption of 1-alkanoic acids in pH 2.2 phosphate buffers was relatively constant over the buffer concentration range of 0.003-0.1 M phosphate.", "contents": "Systems approach to vaginal delivery of drugs IV: methodology for determination of membrane surface pH. A physical model including a diffusional layer in series with the membrane was developed for studying the possible differences between the pH at the membrane surface and that in the bulk solution. Both the membrane-secreted substances (acids and bases) and buffer constituents in the bulk solutions are assumed to contribute to the surface pH. Equations derived for this situation, together with experimental determinations of the acidic dissociation constant of the secreted material, the total secretion flux, the flux of total secreted acidic species, and the diffusion layer thickness, allow estimates to be made of the pH at the membrane surface. With the rabbit vagina, the membrane surface pH was close to that of the bulk solution in most cases. These results were supported by the fact that the absorption of 1-alkanoic acids in pH 2.2 phosphate buffers was relatively constant over the buffer concentration range of 0.003-0.1 M phosphate."}
{"id": "PMID:17717", "title": "Systems approach to vaginal delivery of drugs V: in situ vaginal absorption of 1-alkanoic acids.", "content": "The vaginal absorption of a homologous series of ionizable compounds, the 1-alkanoic acids, was studied using a perfusion method with a rib-cage cell surgically implanted in the rabbit vagina. The absorption rates of these compounds followed first-order kinetics. The physical model previously used for the 1-alkanols, but accounting for the pKa and pH effects in the present case was employed in the analysis of the carboxylic acid data. The aqueous diffusion layer thickness was 0.031 cm. The permeability coefficient for the lipoidal pathway increased 3.5-fold per methylene group. Both values agree reasonably well with those obtained in the alcohol study.", "contents": "Systems approach to vaginal delivery of drugs V: in situ vaginal absorption of 1-alkanoic acids. The vaginal absorption of a homologous series of ionizable compounds, the 1-alkanoic acids, was studied using a perfusion method with a rib-cage cell surgically implanted in the rabbit vagina. The absorption rates of these compounds followed first-order kinetics. The physical model previously used for the 1-alkanols, but accounting for the pKa and pH effects in the present case was employed in the analysis of the carboxylic acid data. The aqueous diffusion layer thickness was 0.031 cm. The permeability coefficient for the lipoidal pathway increased 3.5-fold per methylene group. Both values agree reasonably well with those obtained in the alcohol study."}
{"id": "PMID:17718", "title": "Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines III: nitrazepam.", "content": "The hydrolysis of nitrazepam involves a two-step sequential mechanism. The intermediate is the ring-opened compound resulting from scission of the azomethine bond. The final products are glycine and 2-amino-5-ni-robenzophenone. Recyclization of the intermediate to nitrazepam occurs at pH values above the pKa of the intermediate, in the pH region where the amino group of the intermediate is not protonated. As opposed to chlordiazepoxide and oxazepam, the initial hydrolysis step occurs at the 4,5-bond, not at the 1,2-amide linkage. This difference is attributed to a preferential activation for hydrolysis of the azomethine linkage by the nitro group. The hydrolysis involves an uncatalyzed reaction, specific acid-base catalysis, and general acid-base catalysis for acetate and phosphate buffers.", "contents": "Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines III: nitrazepam. The hydrolysis of nitrazepam involves a two-step sequential mechanism. The intermediate is the ring-opened compound resulting from scission of the azomethine bond. The final products are glycine and 2-amino-5-ni-robenzophenone. Recyclization of the intermediate to nitrazepam occurs at pH values above the pKa of the intermediate, in the pH region where the amino group of the intermediate is not protonated. As opposed to chlordiazepoxide and oxazepam, the initial hydrolysis step occurs at the 4,5-bond, not at the 1,2-amide linkage. This difference is attributed to a preferential activation for hydrolysis of the azomethine linkage by the nitro group. The hydrolysis involves an uncatalyzed reaction, specific acid-base catalysis, and general acid-base catalysis for acetate and phosphate buffers."}
{"id": "PMID:17719", "title": "UV spectrophotometric determination of aminophylline, amobarbital, and ephedrine hydrochloride in an antiasthma capsule preparation.", "content": "A simple and rapid procedure for the determination of aminophylline, amobarbital, and ephedrine hydrochloride in a capsule preparation is described. Aminophylline and amobarbital are determined simultaneously using differential UV spectrophotometry; ephedrine hydrochloride is determined separately after elution from an alginic acid column with 0.1 N hydrochloric acid.", "contents": "UV spectrophotometric determination of aminophylline, amobarbital, and ephedrine hydrochloride in an antiasthma capsule preparation. A simple and rapid procedure for the determination of aminophylline, amobarbital, and ephedrine hydrochloride in a capsule preparation is described. Aminophylline and amobarbital are determined simultaneously using differential UV spectrophotometry; ephedrine hydrochloride is determined separately after elution from an alginic acid column with 0.1 N hydrochloric acid."}
{"id": "PMID:17720", "title": "Stability of aqueous solutions of pirbuterol.", "content": "The hydrolytic degradation of pirbuterol was investigated under saturated oxygen conditions over a wide range of pH values and at different temperatures. Two of the five observed breakdown products were positively identified. The first-order decomposition rate appeared to depend on the rate constants of the four dissociated ionic species. The most stable region for the drug was pH 1-2, where the diprotonated molecule predominated; appropriate thermodynamic parameters were calculated.", "contents": "Stability of aqueous solutions of pirbuterol. The hydrolytic degradation of pirbuterol was investigated under saturated oxygen conditions over a wide range of pH values and at different temperatures. Two of the five observed breakdown products were positively identified. The first-order decomposition rate appeared to depend on the rate constants of the four dissociated ionic species. The most stable region for the drug was pH 1-2, where the diprotonated molecule predominated; appropriate thermodynamic parameters were calculated."}
{"id": "PMID:17721", "title": "Micellar distribution equilibria: ultracentrifugal study of apparent partition coefficients.", "content": "Ultracentrifugation was used for the partial isolation of polysorbate 80 micelles in aqueous media to determine the apparent partition coefficients of various drug species between water and the micellar pseudophase. The ratio of solute concentration in the micelles to that in water was measured for procaine, salicylic acid, sulfapyridine, sulfisoxazole, and sodium 2-naphthalensulfonate over ranges of pH, surfactant concentration, drug concentration, and micelle sedimentation. Apparent partition coefficients for the systems investigated were independent of both drug concentration and surfactant concentration, indicating that the mode(s) of surfactant-drug interaction are essentially invariant over the ranges of systematic variables studied. The method provides a relatively simple and rapid means of quantitatively evaluating drug-surfactant interactions above the CMC, when surfactant and solute can be assayed in mixtures without interference.", "contents": "Micellar distribution equilibria: ultracentrifugal study of apparent partition coefficients. Ultracentrifugation was used for the partial isolation of polysorbate 80 micelles in aqueous media to determine the apparent partition coefficients of various drug species between water and the micellar pseudophase. The ratio of solute concentration in the micelles to that in water was measured for procaine, salicylic acid, sulfapyridine, sulfisoxazole, and sodium 2-naphthalensulfonate over ranges of pH, surfactant concentration, drug concentration, and micelle sedimentation. Apparent partition coefficients for the systems investigated were independent of both drug concentration and surfactant concentration, indicating that the mode(s) of surfactant-drug interaction are essentially invariant over the ranges of systematic variables studied. The method provides a relatively simple and rapid means of quantitatively evaluating drug-surfactant interactions above the CMC, when surfactant and solute can be assayed in mixtures without interference."}
{"id": "PMID:17722", "title": "Physicochemical properties of beta-lactam antibacterials: deuterium solvent isotope effect on penicillin G degradation rate.", "content": "To obtain kinetic evidence on the degradation mechanism of penicillin in aqueous solution, degradation rates of penicillin G in water and deuterium oxide were measured in the pH (pD) range of 4-10. The solvent isotope effect (kH2O/kD2O) of 1.53 below pH (pD) 6 supports the mechanism of water-catalyzed rearrangement of undissociated penicillin G to benzylpenicillenic acid. The spontaneous degradation at neutral pH (pD) and the hydroxide-ion-catalyzed degradation in the alkaline pH (pD) range progress with a deuterium solvent isotope effect (kH2O/kD2O) of 4.5 and 0.59, respectively. This finding indicates the mechanisms of general base-catalyzed hydrolysis by water in the neutral pH range and of nucleophilic attack of the hydroxide ion on the beta-lactam in the alkaline pH range. No significant side-chain dependency was observed in the reaction of penicillins with bases. The solvent isotope studies led to the conclusion that penicillin degradation is catalyzed by a series of bases via general base-catalyzed and nucleophilic mechanisms, depending on their basicity.", "contents": "Physicochemical properties of beta-lactam antibacterials: deuterium solvent isotope effect on penicillin G degradation rate. To obtain kinetic evidence on the degradation mechanism of penicillin in aqueous solution, degradation rates of penicillin G in water and deuterium oxide were measured in the pH (pD) range of 4-10. The solvent isotope effect (kH2O/kD2O) of 1.53 below pH (pD) 6 supports the mechanism of water-catalyzed rearrangement of undissociated penicillin G to benzylpenicillenic acid. The spontaneous degradation at neutral pH (pD) and the hydroxide-ion-catalyzed degradation in the alkaline pH (pD) range progress with a deuterium solvent isotope effect (kH2O/kD2O) of 4.5 and 0.59, respectively. This finding indicates the mechanisms of general base-catalyzed hydrolysis by water in the neutral pH range and of nucleophilic attack of the hydroxide ion on the beta-lactam in the alkaline pH range. No significant side-chain dependency was observed in the reaction of penicillins with bases. The solvent isotope studies led to the conclusion that penicillin degradation is catalyzed by a series of bases via general base-catalyzed and nucleophilic mechanisms, depending on their basicity."}
{"id": "PMID:17723", "title": "GI pharmacology of polyethyleneimine II: motor activity in anesthetized dogs.", "content": "The effects of orally and intravenously administered doses of polyethyleneimine were observed in 18 chloralose-urethan-anesthetized dogs. Polyethyleneimine produced an initial augmentation of rhythmic segmenting gastric antral contractions, a copious flow of gastric mucus, increased segmenting and propulsive activities of the small and large intestines, and occasional micturition and defecation. The gastric corpus and fundic regions became relaxed and enlarged. These events were associated with the prompt appearance of retching. The retching response to oral administration could only be abolished by bilateral vagotomy or bilateral sympathectomy. The skeletal muscle component of retching was blocked by tubocurarine. Intravenous administration of chlorpromazine blocked the retching response and gastric corporal atonia to either intravenous or oral doses of polyethyleneimine. Either oral or intravenous administration of polyethyleneimine produced no detectable changes in the lead II ECG but was associated with marked transient reductions in both mean and pulsatile arterial blood pressures. These depressor effects showed clear tachyphylaxis. In all cases where GI effects were noted, respiration was augmented and erratic in a manner associated with the retching responses.", "contents": "GI pharmacology of polyethyleneimine II: motor activity in anesthetized dogs. The effects of orally and intravenously administered doses of polyethyleneimine were observed in 18 chloralose-urethan-anesthetized dogs. Polyethyleneimine produced an initial augmentation of rhythmic segmenting gastric antral contractions, a copious flow of gastric mucus, increased segmenting and propulsive activities of the small and large intestines, and occasional micturition and defecation. The gastric corpus and fundic regions became relaxed and enlarged. These events were associated with the prompt appearance of retching. The retching response to oral administration could only be abolished by bilateral vagotomy or bilateral sympathectomy. The skeletal muscle component of retching was blocked by tubocurarine. Intravenous administration of chlorpromazine blocked the retching response and gastric corporal atonia to either intravenous or oral doses of polyethyleneimine. Either oral or intravenous administration of polyethyleneimine produced no detectable changes in the lead II ECG but was associated with marked transient reductions in both mean and pulsatile arterial blood pressures. These depressor effects showed clear tachyphylaxis. In all cases where GI effects were noted, respiration was augmented and erratic in a manner associated with the retching responses."}
{"id": "PMID:17729", "title": "Association of in vivo and in vitro propranolol levels in canine Purkinje fibers with antiarrhythmic effects.", "content": "This study has determined the propranolol content of Purkinje fibers associated with antiarrhythmic and electrophysiological actions of the drug both in vivo and in vitro. The minimum effective tissue content of propranolol that consistently reversed a sustained ouabain-induced ventrivular tachycardia in vivo after i.v. propranolol was between 6.7 and 11.1 micron g/g of tissue. Propranolol doses producing Purkinje fiber contents of less than 6.7 micron g/g failed to revert the arrhythmia but did ponotropic responses to 0.5 micron g/kg of isoproterenol. The in vivo minimum effective tissue content was produced in isolated Purkinje fibers perfused with Tyrode's solution containing 1.7 X 10(-6) M propranolol. In Purkinje fibers this concentration of propranolol depressed the rate of phase 4 depolarization previously enhanced by ouabain 2.1 X 10(-7) M. Propranolol, 1.7 X 10(-6) M, did not alter membrane responsiveness and only slightly accelerated repolarization at 5 minutes. Propranolol, 0.85 X 10(-6) M, did not significantly depress the ouabain-enhanced rate of phase 4 depolarization but did attenuate the response to epinephrine through beta blockade. This study indicated that the initial direct action of propranolol in reverting a ouabain-induced ventricular tachycardia to a sinus rhythm in the dog is depression of automaticity.", "contents": "Association of in vivo and in vitro propranolol levels in canine Purkinje fibers with antiarrhythmic effects. This study has determined the propranolol content of Purkinje fibers associated with antiarrhythmic and electrophysiological actions of the drug both in vivo and in vitro. The minimum effective tissue content of propranolol that consistently reversed a sustained ouabain-induced ventrivular tachycardia in vivo after i.v. propranolol was between 6.7 and 11.1 micron g/g of tissue. Propranolol doses producing Purkinje fiber contents of less than 6.7 micron g/g failed to revert the arrhythmia but did ponotropic responses to 0.5 micron g/kg of isoproterenol. The in vivo minimum effective tissue content was produced in isolated Purkinje fibers perfused with Tyrode's solution containing 1.7 X 10(-6) M propranolol. In Purkinje fibers this concentration of propranolol depressed the rate of phase 4 depolarization previously enhanced by ouabain 2.1 X 10(-7) M. Propranolol, 1.7 X 10(-6) M, did not alter membrane responsiveness and only slightly accelerated repolarization at 5 minutes. Propranolol, 0.85 X 10(-6) M, did not significantly depress the ouabain-enhanced rate of phase 4 depolarization but did attenuate the response to epinephrine through beta blockade. This study indicated that the initial direct action of propranolol in reverting a ouabain-induced ventricular tachycardia to a sinus rhythm in the dog is depression of automaticity."}
{"id": "PMID:17732", "title": "Detection of light-induced changes of intracellular ionized calcium concentration in Limulus ventral photoreceptors using arsenazo III.", "content": "1. The metallochromic indicator dye, arsenazo III, was injected intracellularly into Limulus ventral photoreceptor cells to concentrations greater than 1 mM.2. The absorption spectrum (450-750 nm) of the dye in single dark-adapted cells was measured by a scanning microspectrophotometer. When a cell was light-adapted, the absorption of the dye changed; the difference spectrum had two maxima at about 610 and 660 nm, a broad minimum at about 540 nm and an isosbestic point at about 585 nm.3. When intracellular calcium concentration was raised in dark-adapted cells previously injected with arsenazo III, the difference spectum had two maxima at about 610 and 660 nm, a broad minimum at about 530 nm and an isosbestic point at about 585 nm. The injection of Mg(2+) into dark-adapted cells previously injected with the dye induced a difference spectrum that had a single maximum at about 620 nm. Also, decreasing the intracellular pH of cells previously injected with the dye induced a difference spectrum that had a minimum at about 620 nm. The evidence suggests that there is a rise of intracellular ionized calcium when a Limulus ventral photoreceptor is light-adapted.4. The intracellular calcium concentration, [Ca(2+)](1), in light-adapted photoreceptors was estimated to reach at least 10(-4)M by compaing the light-induced difference spectra measured in ventral photoreceptors with a standard curve determined in microcuvettes containing 2mM arsenazo III in 400 mM-KCl, 1 mM-MgCl(2) and 25 mM MOPS at pH 7.0.5. In cells injected to less than 3 mM arsenazo III, light induced a transient decrease in optical transmission at 660 nm (T(660)). This decrease in T(660) indicates that illumination of a ventral photoreceptor normally causes a transient increase of [Ca(2+)](1).6. Arsenazo III was found to be sensitive, selective and rapid enough to measure light-induced changes of intracellular ionized calcium in Limulus ventral photoreceptor cells.", "contents": "Detection of light-induced changes of intracellular ionized calcium concentration in Limulus ventral photoreceptors using arsenazo III. 1. The metallochromic indicator dye, arsenazo III, was injected intracellularly into Limulus ventral photoreceptor cells to concentrations greater than 1 mM.2. The absorption spectrum (450-750 nm) of the dye in single dark-adapted cells was measured by a scanning microspectrophotometer. When a cell was light-adapted, the absorption of the dye changed; the difference spectrum had two maxima at about 610 and 660 nm, a broad minimum at about 540 nm and an isosbestic point at about 585 nm.3. When intracellular calcium concentration was raised in dark-adapted cells previously injected with arsenazo III, the difference spectum had two maxima at about 610 and 660 nm, a broad minimum at about 530 nm and an isosbestic point at about 585 nm. The injection of Mg(2+) into dark-adapted cells previously injected with the dye induced a difference spectrum that had a single maximum at about 620 nm. Also, decreasing the intracellular pH of cells previously injected with the dye induced a difference spectrum that had a minimum at about 620 nm. The evidence suggests that there is a rise of intracellular ionized calcium when a Limulus ventral photoreceptor is light-adapted.4. The intracellular calcium concentration, [Ca(2+)](1), in light-adapted photoreceptors was estimated to reach at least 10(-4)M by compaing the light-induced difference spectra measured in ventral photoreceptors with a standard curve determined in microcuvettes containing 2mM arsenazo III in 400 mM-KCl, 1 mM-MgCl(2) and 25 mM MOPS at pH 7.0.5. In cells injected to less than 3 mM arsenazo III, light induced a transient decrease in optical transmission at 660 nm (T(660)). This decrease in T(660) indicates that illumination of a ventral photoreceptor normally causes a transient increase of [Ca(2+)](1).6. Arsenazo III was found to be sensitive, selective and rapid enough to measure light-induced changes of intracellular ionized calcium in Limulus ventral photoreceptor cells."}
{"id": "PMID:17733", "title": "Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus.", "content": "1. The regulation of cerebrospinal fluid (c.s.f.) bicarbonate concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Decreases in plasma bicarbonate concentration caused relatively small changes in the c.s.f. bicarbonate concentration. 3. Alterations in c.s.f. bicarbonate concentration (c.s.f. HCO3-=9 or 28 m-equiv/l.) were countered by changes in the bicarbonate concentration of the fluid produced by the plexus or in the rate of bicarbonate transport which returned c.s.f. bicarbonate towards normal. 4. There was significant regulation of pH in the choroid plexus fluid during hypocapnia and hypercapnia. 5. Alterations of plasma acid-base status did not significantly alter the potential difference across the choroid plexus. However, the potential difference increased when c.s.f. bicarbonate was increased and decreased when c.s.f. bicarbonate was decreased. 6. The data indicate that the bicarbonate concentration in the c.s.f. is actively regulated by the choroid plexus during acid-base disturbances occurring either systemically or in the c.s.f.", "contents": "Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus. 1. The regulation of cerebrospinal fluid (c.s.f.) bicarbonate concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Decreases in plasma bicarbonate concentration caused relatively small changes in the c.s.f. bicarbonate concentration. 3. Alterations in c.s.f. bicarbonate concentration (c.s.f. HCO3-=9 or 28 m-equiv/l.) were countered by changes in the bicarbonate concentration of the fluid produced by the plexus or in the rate of bicarbonate transport which returned c.s.f. bicarbonate towards normal. 4. There was significant regulation of pH in the choroid plexus fluid during hypocapnia and hypercapnia. 5. Alterations of plasma acid-base status did not significantly alter the potential difference across the choroid plexus. However, the potential difference increased when c.s.f. bicarbonate was increased and decreased when c.s.f. bicarbonate was decreased. 6. The data indicate that the bicarbonate concentration in the c.s.f. is actively regulated by the choroid plexus during acid-base disturbances occurring either systemically or in the c.s.f."}
{"id": "PMID:17734", "title": "Surface potential reflected in both gating and permeation mechanisms of sodium and calcium channels of the tunicate egg cell membrane.", "content": "1. Threshold changes of Na and Ca currents due to various polyvalent cations (stabilizing cations) or H(+) ions were studied in the egg cell membrane of a tunicate, Halocynthia roretzi, by using the voltage-clamp technique.2. With an increase in [Ca](o) or a decrease in pH in the external solution, the current-voltage (I-V) relations for the peak of the Na and Ca currents shifted along the voltage axis in the positive direction. These voltage shifts in the I-V relations, measured at a potential of V((1/2)) where inward current attains its half-maximum, were shown to be identical to shifts in voltage-dependence of the time courses of Na and Ca currents, and also identical to shifts in the inactivation curves of Na current along the voltage axis.3. The shifts in V((1/2)) produced by various polyvalent cations or H(+) ions were analysed by the Gouy-Chapman equation for the diffuse double layer, by assuming that a change in V((1/2)) directly corresponds to a change in the surface double layer potential.4. The V((1/2))-divalent cation concentration relations of Na current were exactly described by the predictions of the theory with a constant value of the surface charge density of 1e(-)/(9 A)(2). The weak stabilizing effects of Mg(2+), Sr(2+) and Ba(2+) were quite similar to each other and were explained in terms of a ;screening' effect. Other divalent cations, such as Ca(2+), Mn(2+) and Ni(2+), showed various different stabilizing effects which were explained in terms of a ;binding' effect. The binding constants (K(1)'s) for Ca(2+), Mn(2+) and Ni(2+) were 0.21, 0.45 and 0.94 M(-1), respectively.5. H(+) ions showed a powerful stabilizing effect upon the Na current with a K(H) of 6 x 10(4)M(-1). This value indicates that the acidic sites around Na channels have a pK(a) of 4.78. La(3+) ions also acted as a strong stabilizer upon the Na current with a K(La) of 15 M(-1). For both H(+) and La(3+), the V((1/2))-concentration relations were also exactly described by the Gouy-Chapman equation with the same charge density of 1e(-)/(9 A)(2) as estimated by varying divalent cations.6. The stabilizing effect of permeant cations such as Ca(2+), Sr(2+) and Ba(2+) on Ca channel currents was analysed. The effect of lowering pH was also studied. It was found that the surface charge density of 1e(-)/(9 A)(2) estimated by Na current is also applicable to the explanation for the V((1/2))-divalent cation concentration or - pH relationships. The estimated binding constants for H(+), Ca(2+) and Sr(2+) were 1.2x10(5), 0.58 and 0.035 M(-1), respectively. Ba(2+) does not bind to charged sites near to the Ca channels.7. It was noticed that a considerable reduction in the conductances of Na and Ca currents occurred in parallel with a stabilizing effect. This reduction was ascribed to a decrease in the concentration of permeant cations at the external surface of the cell membrane, as predicted by the theory of the diffuse double layer. The Goldman, Hodgkin-Katz equation for ionic currents was applied to explain the conductance suppression.8. The conductance suppressions of Na and Ca channel currents due to Ca(2+), Sr(2+) and Ba(2+) were found to be apparent ones, only reflecting decreases in the surface concentration of permeant cations without any changes in the permeability. After correction for the apparent suppression, the real permeability ratio among Ca(2+), Sr(2+) and Ba(2+) for Ca channels was determined as 1.00, 0.56 and 0.21 respectively.9. The conductance suppression of Na current by lowering pH was explained in terms of a real suppression or blocking which is superimposed on the apparent suppression. Considering the surface [Na](o), the plot of P(Na) against the surface pH yielded a blocking curve of Na channel by H(+) ions, which implies that two H(+) ions are necessary to block each Na channel. For Ca channels no real blockage was observed in acidic pH.10. It was concluded from the present experiment that there exists a surface potential capable of affecting both gating and permeation mechanisms of ionic channels in this tunicate egg cell membrane.", "contents": "Surface potential reflected in both gating and permeation mechanisms of sodium and calcium channels of the tunicate egg cell membrane. 1. Threshold changes of Na and Ca currents due to various polyvalent cations (stabilizing cations) or H(+) ions were studied in the egg cell membrane of a tunicate, Halocynthia roretzi, by using the voltage-clamp technique.2. With an increase in [Ca](o) or a decrease in pH in the external solution, the current-voltage (I-V) relations for the peak of the Na and Ca currents shifted along the voltage axis in the positive direction. These voltage shifts in the I-V relations, measured at a potential of V((1/2)) where inward current attains its half-maximum, were shown to be identical to shifts in voltage-dependence of the time courses of Na and Ca currents, and also identical to shifts in the inactivation curves of Na current along the voltage axis.3. The shifts in V((1/2)) produced by various polyvalent cations or H(+) ions were analysed by the Gouy-Chapman equation for the diffuse double layer, by assuming that a change in V((1/2)) directly corresponds to a change in the surface double layer potential.4. The V((1/2))-divalent cation concentration relations of Na current were exactly described by the predictions of the theory with a constant value of the surface charge density of 1e(-)/(9 A)(2). The weak stabilizing effects of Mg(2+), Sr(2+) and Ba(2+) were quite similar to each other and were explained in terms of a ;screening' effect. Other divalent cations, such as Ca(2+), Mn(2+) and Ni(2+), showed various different stabilizing effects which were explained in terms of a ;binding' effect. The binding constants (K(1)'s) for Ca(2+), Mn(2+) and Ni(2+) were 0.21, 0.45 and 0.94 M(-1), respectively.5. H(+) ions showed a powerful stabilizing effect upon the Na current with a K(H) of 6 x 10(4)M(-1). This value indicates that the acidic sites around Na channels have a pK(a) of 4.78. La(3+) ions also acted as a strong stabilizer upon the Na current with a K(La) of 15 M(-1). For both H(+) and La(3+), the V((1/2))-concentration relations were also exactly described by the Gouy-Chapman equation with the same charge density of 1e(-)/(9 A)(2) as estimated by varying divalent cations.6. The stabilizing effect of permeant cations such as Ca(2+), Sr(2+) and Ba(2+) on Ca channel currents was analysed. The effect of lowering pH was also studied. It was found that the surface charge density of 1e(-)/(9 A)(2) estimated by Na current is also applicable to the explanation for the V((1/2))-divalent cation concentration or - pH relationships. The estimated binding constants for H(+), Ca(2+) and Sr(2+) were 1.2x10(5), 0.58 and 0.035 M(-1), respectively. Ba(2+) does not bind to charged sites near to the Ca channels.7. It was noticed that a considerable reduction in the conductances of Na and Ca currents occurred in parallel with a stabilizing effect. This reduction was ascribed to a decrease in the concentration of permeant cations at the external surface of the cell membrane, as predicted by the theory of the diffuse double layer. The Goldman, Hodgkin-Katz equation for ionic currents was applied to explain the conductance suppression.8. The conductance suppressions of Na and Ca channel currents due to Ca(2+), Sr(2+) and Ba(2+) were found to be apparent ones, only reflecting decreases in the surface concentration of permeant cations without any changes in the permeability. After correction for the apparent suppression, the real permeability ratio among Ca(2+), Sr(2+) and Ba(2+) for Ca channels was determined as 1.00, 0.56 and 0.21 respectively.9. The conductance suppression of Na current by lowering pH was explained in terms of a real suppression or blocking which is superimposed on the apparent suppression. Considering the surface [Na](o), the plot of P(Na) against the surface pH yielded a blocking curve of Na channel by H(+) ions, which implies that two H(+) ions are necessary to block each Na channel. For Ca channels no real blockage was observed in acidic pH.10. It was concluded from the present experiment that there exists a surface potential capable of affecting both gating and permeation mechanisms of ionic channels in this tunicate egg cell membrane."}
{"id": "PMID:17735", "title": "Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits.", "content": "1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration. 2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546. 3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1. 4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic.", "contents": "Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits. 1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration. 2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546. 3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1. 4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic."}
{"id": "PMID:17736", "title": "Kinetics of luminal acidification in cortical tubules of the rat kidney.", "content": "1. Some kinetic aspects of renal tubular acidification were studied in proximal and distal tubules of the rat kidney by combining stationary microperfusion methods and continuous measurements of luminal pH changes of phosphate or bicarbonate buffers by means of antimony electrodes. The analysis included the measurement of steady-state pH, steady-state buffer concentrations and acidification half-times. From these data, net rates of tubular bicarbonate reabsorption and of H ion secretion were obtained since it was shown that the rate of phosphate  acidification provides a realistic estimate of H ion secretion. 2. Experiments were performed in control rats, in animals undergoing metabolic acidosis or alkalosis and in control and acidotic rats receiving the carbonic anydrase inhibitor Diamox. 3. In all experiments, the rates of tubular bicarbonate reabsorption and of phosphate acidification (H ion secretion) were proportional to luminal buffer levels. The changes of luminal acid concentrations followed first-order kinetics. 4. Steady-state transepithelial pH differences were reduced in metabolic alkalosis and after diamox but augmented during metabolic acidosis. 5. Acidification half-times were prolonged in metabolic acidosis and after Diamox but remained similar to control levels in metabolic alkalosis. 6. From the observation that both bicarbonate reabsorption and phosphate acidification are similarly affected by these experimental manoeuvres, it is concluded that H ion secretion plays a key role in both transport processes.", "contents": "Kinetics of luminal acidification in cortical tubules of the rat kidney. 1. Some kinetic aspects of renal tubular acidification were studied in proximal and distal tubules of the rat kidney by combining stationary microperfusion methods and continuous measurements of luminal pH changes of phosphate or bicarbonate buffers by means of antimony electrodes. The analysis included the measurement of steady-state pH, steady-state buffer concentrations and acidification half-times. From these data, net rates of tubular bicarbonate reabsorption and of H ion secretion were obtained since it was shown that the rate of phosphate  acidification provides a realistic estimate of H ion secretion. 2. Experiments were performed in control rats, in animals undergoing metabolic acidosis or alkalosis and in control and acidotic rats receiving the carbonic anydrase inhibitor Diamox. 3. In all experiments, the rates of tubular bicarbonate reabsorption and of phosphate acidification (H ion secretion) were proportional to luminal buffer levels. The changes of luminal acid concentrations followed first-order kinetics. 4. Steady-state transepithelial pH differences were reduced in metabolic alkalosis and after diamox but augmented during metabolic acidosis. 5. Acidification half-times were prolonged in metabolic acidosis and after Diamox but remained similar to control levels in metabolic alkalosis. 6. From the observation that both bicarbonate reabsorption and phosphate acidification are similarly affected by these experimental manoeuvres, it is concluded that H ion secretion plays a key role in both transport processes."}
{"id": "PMID:17737", "title": "Mechansims and components of renal tubular acidification.", "content": "1. Renal cortical tubules of control and acetazolamide infused rats were perfused with 100 mM phosphate buffer at pH 5-5. The rate of alkalinization was measured by means of antimony micro-electrodes and was used to compute passive H ion fluxes from lumen to blood across the proximal and distal tubular epithelium. 2. The importance of other ionic movements that might contribute to pH changes of luminal buffers (chloride inflow into the lumen and bicarbonate diffusion across the epithelium) was assessed but found to be minor. H ion movements accounted for the majority of the observed pH changes. 3. H ion permeability of the tubular wall was calculated from the measured H fluxes and transepithelial concentration differences. It was 1-10 cm/sec, several orders of magnitude larger than those for other ions. However, such values are compatible with the mobility of protons in a medium of structure water within the limiting membrane. 4. A kinetic analysis of the mechanism of movement of H ions across the renal tubule is presented on the basis of experiments in which acidification and alkalinization of luminal buffers was followed in stationary microperfusions. The data are compatible with a pump-leak system in the proximal tubule, and with a model with low H ion permeability and a gradient dependent pump in the distal tubule.", "contents": "Mechansims and components of renal tubular acidification. 1. Renal cortical tubules of control and acetazolamide infused rats were perfused with 100 mM phosphate buffer at pH 5-5. The rate of alkalinization was measured by means of antimony micro-electrodes and was used to compute passive H ion fluxes from lumen to blood across the proximal and distal tubular epithelium. 2. The importance of other ionic movements that might contribute to pH changes of luminal buffers (chloride inflow into the lumen and bicarbonate diffusion across the epithelium) was assessed but found to be minor. H ion movements accounted for the majority of the observed pH changes. 3. H ion permeability of the tubular wall was calculated from the measured H fluxes and transepithelial concentration differences. It was 1-10 cm/sec, several orders of magnitude larger than those for other ions. However, such values are compatible with the mobility of protons in a medium of structure water within the limiting membrane. 4. A kinetic analysis of the mechanism of movement of H ions across the renal tubule is presented on the basis of experiments in which acidification and alkalinization of luminal buffers was followed in stationary microperfusions. The data are compatible with a pump-leak system in the proximal tubule, and with a model with low H ion permeability and a gradient dependent pump in the distal tubule."}
{"id": "PMID:17738", "title": "A mathematical model for counter-current multiplications in the swim-bladder.", "content": "1. A computer model for swim-bladder gas filling has been developed. Phenomenological descriptions of the Root effect (pH-dependent O2 capacity of fish haemoglobin), of the lactic acid production in the gas gland and of the geometry of the rete mirabile are incorporated in the general counter-current equations to give a comprehensive model of gas filling. 2. It is known that pH along the rete is not constant, as supposed in an earlier gas-filling model. It is also known that the Root shift reaction has a different half-time model. It is also known that the Root shift reaction has a different half-time depending on whether the haemoglobin absorbs or releases O2. These particular effects are accounted for in the present model. 3. The model gives gas filling rate and maximum swim-bladder pressure for CO2, O2 and N2. The partial pressure of these gases as well as the concentration of lactic acid and the pH along the rete are also calculated. 4. The model reproduces quite accurately experimental values for gas-filling rate in eel, together with lactic acid, CO2 and O2 concentrations measured at the rete end-points. There is also good correlation between maximum predicted stable swim-bladder pressure and maximum recorded depth for four fishes investigated (r=0-937; P=0-06). 5. The model predicts an enhancement of O2 filling rate and maximum swim-bladder pressure of at least 4 when the reaction rates of the Root shift in eel haemoglobin are 0-2 sec (Root-off) and 10 sec (Root-on), as compared to an instantaneous Root shift. 6. With a swim-bladder pressure of 1 atm and Root-shift reaction rates of equal magnitude, the po2-profile along the rete is nearly linear. When the reaction rates are such as found experimentally in eel haemoglobin, the po2 along the rete is non-linear, with a maximum of approximately 2 atm near the bladder pole of the rete. An experimental verification of this maximum will constitute a crucial test of the model. 7. The calculations show that blood flow through rete can regulate both gas-filling rate and stable swim-bladder pressure. At high pressure, the main factor limiting gas filling is loss of gas through back diffusion along the rete. 8. Maximum po2 in the swim-bladder is highly dependent upon the Root effect. If the Root effect persists up to about 100 atm, as seems to be the case blue hake, maximum po2 is more than 200 atm. When the Root effect is abolished at 10 atm, as is expected in eel, the maximum po2 drops to about 30 atm. 9. The pN2 in the bladder can reach 10-15 atm depending on blood flow, whereas PCO2 will not exceed 1 atm.", "contents": "A mathematical model for counter-current multiplications in the swim-bladder. 1. A computer model for swim-bladder gas filling has been developed. Phenomenological descriptions of the Root effect (pH-dependent O2 capacity of fish haemoglobin), of the lactic acid production in the gas gland and of the geometry of the rete mirabile are incorporated in the general counter-current equations to give a comprehensive model of gas filling. 2. It is known that pH along the rete is not constant, as supposed in an earlier gas-filling model. It is also known that the Root shift reaction has a different half-time model. It is also known that the Root shift reaction has a different half-time depending on whether the haemoglobin absorbs or releases O2. These particular effects are accounted for in the present model. 3. The model gives gas filling rate and maximum swim-bladder pressure for CO2, O2 and N2. The partial pressure of these gases as well as the concentration of lactic acid and the pH along the rete are also calculated. 4. The model reproduces quite accurately experimental values for gas-filling rate in eel, together with lactic acid, CO2 and O2 concentrations measured at the rete end-points. There is also good correlation between maximum predicted stable swim-bladder pressure and maximum recorded depth for four fishes investigated (r=0-937; P=0-06). 5. The model predicts an enhancement of O2 filling rate and maximum swim-bladder pressure of at least 4 when the reaction rates of the Root shift in eel haemoglobin are 0-2 sec (Root-off) and 10 sec (Root-on), as compared to an instantaneous Root shift. 6. With a swim-bladder pressure of 1 atm and Root-shift reaction rates of equal magnitude, the po2-profile along the rete is nearly linear. When the reaction rates are such as found experimentally in eel haemoglobin, the po2 along the rete is non-linear, with a maximum of approximately 2 atm near the bladder pole of the rete. An experimental verification of this maximum will constitute a crucial test of the model. 7. The calculations show that blood flow through rete can regulate both gas-filling rate and stable swim-bladder pressure. At high pressure, the main factor limiting gas filling is loss of gas through back diffusion along the rete. 8. Maximum po2 in the swim-bladder is highly dependent upon the Root effect. If the Root effect persists up to about 100 atm, as seems to be the case blue hake, maximum po2 is more than 200 atm. When the Root effect is abolished at 10 atm, as is expected in eel, the maximum po2 drops to about 30 atm. 9. The pN2 in the bladder can reach 10-15 atm depending on blood flow, whereas PCO2 will not exceed 1 atm."}
{"id": "PMID:17739", "title": "Contraction and recovery of living muscles studies by 31P nuclear magnetic resonance.", "content": "1. Phosphorus nuclear magnetic resonance ((31)P NMR) can be used to measure the concentrations of phosphorus-containing metabolites within living tissue. We have developed methods for maintaining muscles in physiological condition, stimulating them and recording tension while at the same time accumulating their (31)P NMR spectra. Experiments were performed on frog sartorii and frog and toad gastrocnemii at 4 degrees C.2. The NMR signals from (31)P (the naturally occurring phosphorus) is weak, and signal averaging is required. In order to follow the time course of reactions it is necessary to maintain the muscles in a steady state for many hours while they are undergoing repeated contractions. Signals were accumulated in separate computer bins according to time after initiation of contraction. By these means spectra were obtained which corresponded to the different intervals during the contraction and recovery cycle.3. In the absence of stimulation, the spectra of frog sartorius muscles and of their extracts indicated concentrations of adenosine triphosphate (ATP), phosphoryl creatine (PCr), inorganic orthophosphate (P(i)) and sugar phosphates (sugar P) which are in reasonable agreement with the values obtained by chemical analysis.4. We have confirmed that unidentified resonances representing unknown compounds appear in the spectra of both frog and toad muscle; one of these is much larger in spectra from toad than from frog. We have found an additional small, unidentified resonance which appears to be specific to toad muscle.5. Spectra accumulated during actual contractions (1 s tetani every 2 min) did not differ dramatically from those accumulated throughout the 2 min cycle of contraction and partial recovery.6. Following 25 s tetanii, approximately 20% of the PCr had been hydrolysed; it was then rebuilt exponentially with a half-time of about 10 min. The increase in [P(i)] immediately after contraction and the time course of its disappearance corresponded to the changes in [PCr]. During the later half of the recovery period the concentration of P(i) was reduced to below that in resting muscle. The [sugar P] remained very high ( approximately 4 mmol kg(-1)) throughout the 56 min interval between contractions.7. When frog sartorii were tetanized for 1 s every 2 min, the changes in [PCr] and [P(i)] between contractions could not be observed because too little signal was obtained from these small muscles. However, when toad gastrocnemii were similarly stimulated, the changes in these compounds could be readily detected and were even greater than expected.8. The position of the P(i) resonance can be used to monitor intracellular pH and changes in pH. Under the conditions of our experiments the average intracellular pH in unstimulated frog sartorius muscles was 7.5. After a 25 s tetanus this was observed to move in the acid direction by a few tenths of a pH unit and to return to its pre-stimulation value before the end of the recovery period. After a 1 s contraction of toad gastrocnemius the environment of P(i) became slightly more alkaline for the first few seconds.", "contents": "Contraction and recovery of living muscles studies by 31P nuclear magnetic resonance. 1. Phosphorus nuclear magnetic resonance ((31)P NMR) can be used to measure the concentrations of phosphorus-containing metabolites within living tissue. We have developed methods for maintaining muscles in physiological condition, stimulating them and recording tension while at the same time accumulating their (31)P NMR spectra. Experiments were performed on frog sartorii and frog and toad gastrocnemii at 4 degrees C.2. The NMR signals from (31)P (the naturally occurring phosphorus) is weak, and signal averaging is required. In order to follow the time course of reactions it is necessary to maintain the muscles in a steady state for many hours while they are undergoing repeated contractions. Signals were accumulated in separate computer bins according to time after initiation of contraction. By these means spectra were obtained which corresponded to the different intervals during the contraction and recovery cycle.3. In the absence of stimulation, the spectra of frog sartorius muscles and of their extracts indicated concentrations of adenosine triphosphate (ATP), phosphoryl creatine (PCr), inorganic orthophosphate (P(i)) and sugar phosphates (sugar P) which are in reasonable agreement with the values obtained by chemical analysis.4. We have confirmed that unidentified resonances representing unknown compounds appear in the spectra of both frog and toad muscle; one of these is much larger in spectra from toad than from frog. We have found an additional small, unidentified resonance which appears to be specific to toad muscle.5. Spectra accumulated during actual contractions (1 s tetani every 2 min) did not differ dramatically from those accumulated throughout the 2 min cycle of contraction and partial recovery.6. Following 25 s tetanii, approximately 20% of the PCr had been hydrolysed; it was then rebuilt exponentially with a half-time of about 10 min. The increase in [P(i)] immediately after contraction and the time course of its disappearance corresponded to the changes in [PCr]. During the later half of the recovery period the concentration of P(i) was reduced to below that in resting muscle. The [sugar P] remained very high ( approximately 4 mmol kg(-1)) throughout the 56 min interval between contractions.7. When frog sartorii were tetanized for 1 s every 2 min, the changes in [PCr] and [P(i)] between contractions could not be observed because too little signal was obtained from these small muscles. However, when toad gastrocnemii were similarly stimulated, the changes in these compounds could be readily detected and were even greater than expected.8. The position of the P(i) resonance can be used to monitor intracellular pH and changes in pH. Under the conditions of our experiments the average intracellular pH in unstimulated frog sartorius muscles was 7.5. After a 25 s tetanus this was observed to move in the acid direction by a few tenths of a pH unit and to return to its pre-stimulation value before the end of the recovery period. After a 1 s contraction of toad gastrocnemius the environment of P(i) became slightly more alkaline for the first few seconds."}
{"id": "PMID:17740", "title": "Micro-electrode measurement of the intracellular pH and buffering power of mouse soleus muscle fibres.", "content": "1. The intracellular pH (pHi) of surface fibres of the mouse soleus muscle has been measured in vitro using recessed-tip pH-sensitive microelectrodes. 2. In 5% CO2 and pH 7-40, the mean pHi was 7-07 +/- 0-007 (S.E. of mean) at 37 degrees C and 7-23 +/- 0-01 at 28 degrees C. The difference between these tow values is the same as the change in neutral pH between 37 and 28 degrees C. 3. Alteration of the CO2 level at constant external pH caused a biphasic change in pHi with a rapid displacement followed by a slower partial recovery. Because the recovery was incomplete, different stable pHi values were recorded at different CO2 levels, the higher the CO2 the lower the pHi. The differences in pHi were highly significant both at 37 and 28 degrees C. 4. Alteration of the CO2 level at constant external pH also changed the membrane potential (Em), an increase in CO2 leading to an increased Em. The dependence of Em on the CO2 level was much smaller in the fast-twitch muscle, extensor digitorum longus, than in soleus. 5. Changing external pH, either by alteration of the bicarbonate or CO2 level of the Ringer solution, caused pHi to change by a mean 38-7% of the external pH change. The change in pHi was accomplished about 10 times more rapidly, and in the same direction, by altering CO2 than by altering the bicarbonate. 6. Application of external NH3 and NH+4 caused a rapid intracellular alkalinization followed by a slower acidification. On removal of external NH3 and NH+4, there was a large and rapid acdification, followed by a fairly rapid recovery in pHi. 7. The size of the pHi changes occurring on alteration of the CO2 level at both constant external pH and constant external bicarbonate, and on removal of external NH3 and NH+4, suggests a non-CO2 buffering power of 45m-equiv H+ ions/pH unit per litre and a constant-CO2 buffering power of 58 m-equiv H+ ions/pH unit per litre. The buffering power was apparently unaffected by a change in temperature between 37 and 28 degrees C. 8. It was concluded that H+ ions are not passively distributed across the muscle cell membrane, and that the pHi is closely controlled by the active transport of H+, OH- or HCO-3 ions.", "contents": "Micro-electrode measurement of the intracellular pH and buffering power of mouse soleus muscle fibres. 1. The intracellular pH (pHi) of surface fibres of the mouse soleus muscle has been measured in vitro using recessed-tip pH-sensitive microelectrodes. 2. In 5% CO2 and pH 7-40, the mean pHi was 7-07 +/- 0-007 (S.E. of mean) at 37 degrees C and 7-23 +/- 0-01 at 28 degrees C. The difference between these tow values is the same as the change in neutral pH between 37 and 28 degrees C. 3. Alteration of the CO2 level at constant external pH caused a biphasic change in pHi with a rapid displacement followed by a slower partial recovery. Because the recovery was incomplete, different stable pHi values were recorded at different CO2 levels, the higher the CO2 the lower the pHi. The differences in pHi were highly significant both at 37 and 28 degrees C. 4. Alteration of the CO2 level at constant external pH also changed the membrane potential (Em), an increase in CO2 leading to an increased Em. The dependence of Em on the CO2 level was much smaller in the fast-twitch muscle, extensor digitorum longus, than in soleus. 5. Changing external pH, either by alteration of the bicarbonate or CO2 level of the Ringer solution, caused pHi to change by a mean 38-7% of the external pH change. The change in pHi was accomplished about 10 times more rapidly, and in the same direction, by altering CO2 than by altering the bicarbonate. 6. Application of external NH3 and NH+4 caused a rapid intracellular alkalinization followed by a slower acidification. On removal of external NH3 and NH+4, there was a large and rapid acdification, followed by a fairly rapid recovery in pHi. 7. The size of the pHi changes occurring on alteration of the CO2 level at both constant external pH and constant external bicarbonate, and on removal of external NH3 and NH+4, suggests a non-CO2 buffering power of 45m-equiv H+ ions/pH unit per litre and a constant-CO2 buffering power of 58 m-equiv H+ ions/pH unit per litre. The buffering power was apparently unaffected by a change in temperature between 37 and 28 degrees C. 8. It was concluded that H+ ions are not passively distributed across the muscle cell membrane, and that the pHi is closely controlled by the active transport of H+, OH- or HCO-3 ions."}
{"id": "PMID:17741", "title": "The effect of temperature on the potential difference and input resistance of rat seminiferous tubules.", "content": "1. The p.d. of rat seminiferous tubules was 5.86 +/- 0.15 mV, lumen negative, at 33 degrees C and varied linearly with temperature between 24 and 37 degrees C, exhibiting an apparent Q(10) (25-35 degrees C) of 2.0 with a slope of 0.43 mV/ degrees C. Exposing testes to a temperature of 37-43 degrees C resulted in an initial hyperpolarization followed by depolarization of the tubules. These changes were more rapid in testes exposed to 41-43 degrees C than in testes exposed to 37-39 degrees C.2. The R(in) of seminiferous tubules was 198 +/- 7.8 kOmega at a testis temperature of 33 degrees C. The R(in) decreased when testes were maintained at 37 and 41 degrees C, the rate of decrease being similar to the rate of depolarization.3. Exposing testes to deep body temperature by unilateral surgical cryptorchidism caused a reduction of 30 and 64% in tubular p.d. and R(in) respectively when measured 24 hr after surgery. Exposure to deep body temperature for up to 4 days did not cause any further change in either parameter.4. There was no evidence that lanthanum penetrated through the Sertoli cell tight junctions after exposing testes to 41 degrees C for up to 30 min.5. The results indicate that the seminiferous tubule p.d. is maintained by a temperature-sensitive, cellular mechanism. Exposing testes to deep body temperature or above depolarized the tubules and increased their permeability.", "contents": "The effect of temperature on the potential difference and input resistance of rat seminiferous tubules. 1. The p.d. of rat seminiferous tubules was 5.86 +/- 0.15 mV, lumen negative, at 33 degrees C and varied linearly with temperature between 24 and 37 degrees C, exhibiting an apparent Q(10) (25-35 degrees C) of 2.0 with a slope of 0.43 mV/ degrees C. Exposing testes to a temperature of 37-43 degrees C resulted in an initial hyperpolarization followed by depolarization of the tubules. These changes were more rapid in testes exposed to 41-43 degrees C than in testes exposed to 37-39 degrees C.2. The R(in) of seminiferous tubules was 198 +/- 7.8 kOmega at a testis temperature of 33 degrees C. The R(in) decreased when testes were maintained at 37 and 41 degrees C, the rate of decrease being similar to the rate of depolarization.3. Exposing testes to deep body temperature by unilateral surgical cryptorchidism caused a reduction of 30 and 64% in tubular p.d. and R(in) respectively when measured 24 hr after surgery. Exposure to deep body temperature for up to 4 days did not cause any further change in either parameter.4. There was no evidence that lanthanum penetrated through the Sertoli cell tight junctions after exposing testes to 41 degrees C for up to 30 min.5. The results indicate that the seminiferous tubule p.d. is maintained by a temperature-sensitive, cellular mechanism. Exposing testes to deep body temperature or above depolarized the tubules and increased their permeability."}
{"id": "PMID:17742", "title": "Hyperpolarizing effects of dopamine on chemoreceptor nerve endings from cat and rabbit carotid bodies in vitro.", "content": "1. The effects of dopamine on DC potential changes recorded from the carotid sinus nerve were studied in vitro using carotid bodies and associated sinus nerves removed from anaesthetized cats and rabbits.2. The carotid body was placed in one compartment of a superfusion chamber and was superfused with buffered salt solution. The carotid sinus nerve was led into an adjoining compartment, containing lightweight mineral oil, for recording DC potential changes with chlorided silver electrodes.3. Dopamine injected into the superfusing solution in amounts of 50-250 mug caused hyperpolarization of the DC potential. This effect occurred repeatedly in each preparation, the maximum number of tests in any one preparation being twenty-seven.4. In the same preparations, acetylcholine (50-100 mug) and NaCN (10-20 mug) caused depolarizations of the DC potential, effects that have been described by others.5. The hyperpolarizing effects of dopamine were reduced or abolished by the alpha-adrenergic antagonists, dihydroergotamine (10-100 mug/ml.) and phenoxybenzamine (5 mug/ml.) and the dopamine antagonist droperidol (10-25 mug/ml.).6. The results indicate that the inhibitory effects of dopamine on the frequency of carotid body chemosensory discharges in cats and rabbits are due to hyperpolarization of chemoreceptor afferent nerve endings and not necessarily to local vascular effects in the carotid body.", "contents": "Hyperpolarizing effects of dopamine on chemoreceptor nerve endings from cat and rabbit carotid bodies in vitro. 1. The effects of dopamine on DC potential changes recorded from the carotid sinus nerve were studied in vitro using carotid bodies and associated sinus nerves removed from anaesthetized cats and rabbits.2. The carotid body was placed in one compartment of a superfusion chamber and was superfused with buffered salt solution. The carotid sinus nerve was led into an adjoining compartment, containing lightweight mineral oil, for recording DC potential changes with chlorided silver electrodes.3. Dopamine injected into the superfusing solution in amounts of 50-250 mug caused hyperpolarization of the DC potential. This effect occurred repeatedly in each preparation, the maximum number of tests in any one preparation being twenty-seven.4. In the same preparations, acetylcholine (50-100 mug) and NaCN (10-20 mug) caused depolarizations of the DC potential, effects that have been described by others.5. The hyperpolarizing effects of dopamine were reduced or abolished by the alpha-adrenergic antagonists, dihydroergotamine (10-100 mug/ml.) and phenoxybenzamine (5 mug/ml.) and the dopamine antagonist droperidol (10-25 mug/ml.).6. The results indicate that the inhibitory effects of dopamine on the frequency of carotid body chemosensory discharges in cats and rabbits are due to hyperpolarization of chemoreceptor afferent nerve endings and not necessarily to local vascular effects in the carotid body."}
{"id": "PMID:17743", "title": "Interacting effects of temperature and extracellular calcium on the spontaneous release of transmitter at the frog neuromuscular junction.", "content": "1. Temperature has a characteristic effect on the frequency of m.e.p.p.s at the frog neuromuscular junction; the spontaneous release of transmitter is not affected by temperature changes below 10 degrees C whereas the system is highly temperature-sensitive above 20 degrees C.2. A very similar result is obtained when the experiment is repeated in saline containing Ca(2+) buffered at 5 x 10(-7)M, suggesting that it is unlikely that the major action of temperature is to cause an increase in Ca(2+) influx.3. It is suggested that the main effect of temperature at the presynaptic terminals is a modification of [Ca(2+)](i) by an action on intracellular Ca(2+) stores.4. The interacting effects of theophylline and the divalent cation ionophore A23187 on m.e.p.p. frequency suggest that intracellular Ca(2+) stores, in addition to the mitochondria, may well be of importance in controlling [Ca(2+)](i).5. Changes in [Ca(2+)](o) produce a modification of m.e.p.p. frequency, but the details of the response are dependent on temperature. The spontaneous release of transmitter is most sensitive to an increase in [Ca(2+)](o) at 23 degrees C, whereas the greater effect is found at 13 degrees C when [Ca(2+)](o) is lowered.6. It is suggested (i) that m.e.p.p. frequency is primarily determined by [Ca(2+)](i) at the presynaptic terminals, (ii) that the presynaptic terminals are normally able to maintain [Ca(2+)](i) almost constant in spite of increases in Ca influx associated with ionophore treatment or with a rise in [Ca(2+)](o). However, if the steady-state position of [Ca(2+)](i) is previously raised by an increased efflux from intracellular stores (produced by elevated temperature or theophylline pre-treatment), increased influx causes a rise in both [Ca(2+)](i) and in m.e.p.p. frequency.", "contents": "Interacting effects of temperature and extracellular calcium on the spontaneous release of transmitter at the frog neuromuscular junction. 1. Temperature has a characteristic effect on the frequency of m.e.p.p.s at the frog neuromuscular junction; the spontaneous release of transmitter is not affected by temperature changes below 10 degrees C whereas the system is highly temperature-sensitive above 20 degrees C.2. A very similar result is obtained when the experiment is repeated in saline containing Ca(2+) buffered at 5 x 10(-7)M, suggesting that it is unlikely that the major action of temperature is to cause an increase in Ca(2+) influx.3. It is suggested that the main effect of temperature at the presynaptic terminals is a modification of [Ca(2+)](i) by an action on intracellular Ca(2+) stores.4. The interacting effects of theophylline and the divalent cation ionophore A23187 on m.e.p.p. frequency suggest that intracellular Ca(2+) stores, in addition to the mitochondria, may well be of importance in controlling [Ca(2+)](i).5. Changes in [Ca(2+)](o) produce a modification of m.e.p.p. frequency, but the details of the response are dependent on temperature. The spontaneous release of transmitter is most sensitive to an increase in [Ca(2+)](o) at 23 degrees C, whereas the greater effect is found at 13 degrees C when [Ca(2+)](o) is lowered.6. It is suggested (i) that m.e.p.p. frequency is primarily determined by [Ca(2+)](i) at the presynaptic terminals, (ii) that the presynaptic terminals are normally able to maintain [Ca(2+)](i) almost constant in spite of increases in Ca influx associated with ionophore treatment or with a rise in [Ca(2+)](o). However, if the steady-state position of [Ca(2+)](i) is previously raised by an increased efflux from intracellular stores (produced by elevated temperature or theophylline pre-treatment), increased influx causes a rise in both [Ca(2+)](i) and in m.e.p.p. frequency."}
{"id": "PMID:17744", "title": "The effects on breathing of alternate breaths of air and a carbon dioxide rich gas mixture in anaesthetized cats.", "content": "1. An in vivo pH electrode was used to assess the effect in anaesthetized cats of the administration of 5% CO(2) (21% O(2), balance N(2)) and air as alternate inspirates upon the time course of the carotid arterial pH, and by inference, the P(CO2).2. This method of administration of CO(2) and air resulted in a lowering of the recorded pH with the production of oscillations of twice the duration seen on air alone. These larger oscillations had a period of two respiratory cycles and their amplitude was approximately twice that of normal oscillations.3. The respiratory response consisted in all cases of an increase in mean tidal volume and ventilation, and in 50-60% of recorded runs, of a highly specific sequence of tidal volume changes. The specific sequence was composed of alternately larger and smaller breaths which persisted while the larger oscillations continued.4. The use of the in vivo pH electrode made it possible to determine whether or not the tidal volume alternation was a result of sensitivity to carotid arterial P(CO2) oscillations. By diverting the carotid arterial blood through a mixing chamber the amplitude of the double (respiratory) period oscillations was, in some cases, reduced but not eliminated. In these cases the specific pattern of tidal volume changes was still present in 60% of trials. In the cases where the pH fluctuations were completely eliminated the specific respiratory pattern was never present.5. Average breath to breath differences in tidal volume seen during control runs with large oscillations present ranged in size from 3.6 to 8.6% of the mean tidal volume. When the oscillations were completely eliminated by means of the mixing chamber the breath by breath differences only ranged from 0.2 to 2.7% of mean tidal volume. The change was highly significant.6. Mean tidal volume and ventilation were not altered by eliminating the large (double period) oscillations.7. It has been shown that the tidal volume is made to change from breath to breath in a persistent manner when there are recurrent changes in carotid arterial blood chemistry. The effects on respiration involve vascular receptors above the mid carotid arterial region. It is argued that the effects involve the sensitivity of the carotid bodies to rapid (within breath) changes in P(a, CO2). There appears to be no significant effect on mean ventilation of the dynamic component of the arterial P(CO2) changes produced in these experiments.", "contents": "The effects on breathing of alternate breaths of air and a carbon dioxide rich gas mixture in anaesthetized cats. 1. An in vivo pH electrode was used to assess the effect in anaesthetized cats of the administration of 5% CO(2) (21% O(2), balance N(2)) and air as alternate inspirates upon the time course of the carotid arterial pH, and by inference, the P(CO2).2. This method of administration of CO(2) and air resulted in a lowering of the recorded pH with the production of oscillations of twice the duration seen on air alone. These larger oscillations had a period of two respiratory cycles and their amplitude was approximately twice that of normal oscillations.3. The respiratory response consisted in all cases of an increase in mean tidal volume and ventilation, and in 50-60% of recorded runs, of a highly specific sequence of tidal volume changes. The specific sequence was composed of alternately larger and smaller breaths which persisted while the larger oscillations continued.4. The use of the in vivo pH electrode made it possible to determine whether or not the tidal volume alternation was a result of sensitivity to carotid arterial P(CO2) oscillations. By diverting the carotid arterial blood through a mixing chamber the amplitude of the double (respiratory) period oscillations was, in some cases, reduced but not eliminated. In these cases the specific pattern of tidal volume changes was still present in 60% of trials. In the cases where the pH fluctuations were completely eliminated the specific respiratory pattern was never present.5. Average breath to breath differences in tidal volume seen during control runs with large oscillations present ranged in size from 3.6 to 8.6% of the mean tidal volume. When the oscillations were completely eliminated by means of the mixing chamber the breath by breath differences only ranged from 0.2 to 2.7% of mean tidal volume. The change was highly significant.6. Mean tidal volume and ventilation were not altered by eliminating the large (double period) oscillations.7. It has been shown that the tidal volume is made to change from breath to breath in a persistent manner when there are recurrent changes in carotid arterial blood chemistry. The effects on respiration involve vascular receptors above the mid carotid arterial region. It is argued that the effects involve the sensitivity of the carotid bodies to rapid (within breath) changes in P(a, CO2). There appears to be no significant effect on mean ventilation of the dynamic component of the arterial P(CO2) changes produced in these experiments."}
{"id": "PMID:17745", "title": "Further observations on an ether-O-oxidase, formerly called alkyl etherase, from liver tissue.", "content": "1. The microsomal enzyme from liver previously called an \"etherase\" is now described more accurately as an ether-O-oxidase. It has been investigated further to free it from the membranes in aqueous solution and to try to define its physiological substrate. 2. After a variety of attempts with detergents, etc., the enzyme was obtained in impure solution from precipitation with 35-45% (NH4)2SO4 solution after a short digestion at room temperature. 3. When a suitably reinforced the enzyme in solution forms citrate from added ethyl ether, as it does in membranous form. This indicates the intermediary formation of acetyl CoA. 4. The enzyme in solution is unstable, though some activity remains after standing at 0degrees C for 2-3 days. Activity is lost rapidly by deep freezing, exposure to 2M-NaCl and at a pH more acid than pH 5-0. 5. The enzyme does not appear to be a known oxidase obtainable from liver microsomes; it is not for instance part of the inducible mixed oxygenase system, nor a peroxidase or catalase. 6. Since there were some similarities in stability with enzymes dealing with protozoal plasmalogens, or with lanosterol or cholesterol, we were led to explore these substrates in detail, with negative results. But a specimen of cholesterol oxidase from the branching bacterium Nocardia gave O-oxidation with diethylether. 7. The enzyme is present in the livers of all four animals examined, namely the rat, pig, guinea-pig and pigeon, but not in kidney or brain. 8. The enzyme takes up O2 with some compounds containing O-me groups. 9. The hypothesis is advanced that this normal oxidase in liver membranes exists to deal with some substances from plant sources which might prove toxic upon entering the circulation.", "contents": "Further observations on an ether-O-oxidase, formerly called alkyl etherase, from liver tissue. 1. The microsomal enzyme from liver previously called an \"etherase\" is now described more accurately as an ether-O-oxidase. It has been investigated further to free it from the membranes in aqueous solution and to try to define its physiological substrate. 2. After a variety of attempts with detergents, etc., the enzyme was obtained in impure solution from precipitation with 35-45% (NH4)2SO4 solution after a short digestion at room temperature. 3. When a suitably reinforced the enzyme in solution forms citrate from added ethyl ether, as it does in membranous form. This indicates the intermediary formation of acetyl CoA. 4. The enzyme in solution is unstable, though some activity remains after standing at 0degrees C for 2-3 days. Activity is lost rapidly by deep freezing, exposure to 2M-NaCl and at a pH more acid than pH 5-0. 5. The enzyme does not appear to be a known oxidase obtainable from liver microsomes; it is not for instance part of the inducible mixed oxygenase system, nor a peroxidase or catalase. 6. Since there were some similarities in stability with enzymes dealing with protozoal plasmalogens, or with lanosterol or cholesterol, we were led to explore these substrates in detail, with negative results. But a specimen of cholesterol oxidase from the branching bacterium Nocardia gave O-oxidation with diethylether. 7. The enzyme is present in the livers of all four animals examined, namely the rat, pig, guinea-pig and pigeon, but not in kidney or brain. 8. The enzyme takes up O2 with some compounds containing O-me groups. 9. The hypothesis is advanced that this normal oxidase in liver membranes exists to deal with some substances from plant sources which might prove toxic upon entering the circulation."}
{"id": "PMID:17746", "title": "5-Aryl-1,5-dihydro-2H-1,4-benzodiazepin-2-one derivatives as antianxiety agents.", "content": "A new series of 7-chloro- and 7-nitro-5-methoxy-5-phenyl-1,5-dihydro-2H-1,4-benzodiazepin-2-ones (7a, c--e) was synthesized and found to have potent antipentylenetetrazole activity. These compounds were also employed as intermediates in the synthesis of 3-substituted 1,3-dihydro-1,4-benzodiazepin-2-ones (8f--v).", "contents": "5-Aryl-1,5-dihydro-2H-1,4-benzodiazepin-2-one derivatives as antianxiety agents. A new series of 7-chloro- and 7-nitro-5-methoxy-5-phenyl-1,5-dihydro-2H-1,4-benzodiazepin-2-ones (7a, c--e) was synthesized and found to have potent antipentylenetetrazole activity. These compounds were also employed as intermediates in the synthesis of 3-substituted 1,3-dihydro-1,4-benzodiazepin-2-ones (8f--v)."}
{"id": "PMID:17747", "title": "3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities.", "content": "The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series.", "contents": "3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities. The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series."}
{"id": "PMID:17748", "title": "A comparison of the antiserotonin, antihistamine, and anticholinergic activity of cyproheptadine with analogues having furan nuclei fused to the 10,11-vinylene bridge.", "content": "A series of cyproheptadine derivatives having furan nuclei fused to the 10,11-vinylene bridge has been prepared. None of the compounds retain the potent antiserotonin and antihistaminic actions of cyproheptadine. 1-methyl-4-(1-methyl-8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-ylidene)piperidine (7), 1-methyl-4-(1,3-dihydro-1-oxo-8H-[3,4:6,7]cycloheptal[1,2-c]furan-8-ylidene)piperidine (10), and its reduction product 11 retained the peripheral anticholinergic activity of cyproheptadine.", "contents": "A comparison of the antiserotonin, antihistamine, and anticholinergic activity of cyproheptadine with analogues having furan nuclei fused to the 10,11-vinylene bridge. A series of cyproheptadine derivatives having furan nuclei fused to the 10,11-vinylene bridge has been prepared. None of the compounds retain the potent antiserotonin and antihistaminic actions of cyproheptadine. 1-methyl-4-(1-methyl-8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-ylidene)piperidine (7), 1-methyl-4-(1,3-dihydro-1-oxo-8H-[3,4:6,7]cycloheptal[1,2-c]furan-8-ylidene)piperidine (10), and its reduction product 11 retained the peripheral anticholinergic activity of cyproheptadine."}
{"id": "PMID:17749", "title": "Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2-alkylaminomethylbenzodioxans, competitive alpha-adrenergic antagonists.", "content": "The optical isomers of alpha-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzyloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the alpha-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine.", "contents": "Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2-alkylaminomethylbenzodioxans, competitive alpha-adrenergic antagonists. The optical isomers of alpha-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzyloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the alpha-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine."}
{"id": "PMID:17750", "title": "Synthesis and biological evaluation of a tetrahydroisoquinoline derivative possessing selective beta2-adrenergic agonist activity.", "content": "This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. The relative activities in relaxation of guinea pig trachea is 1 greater than 2 greater than 3 while in the chronotropic response in guinea pig atria the relative order of activity is 1 greater than 3 greater than 2.", "contents": "Synthesis and biological evaluation of a tetrahydroisoquinoline derivative possessing selective beta2-adrenergic agonist activity. This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. The relative activities in relaxation of guinea pig trachea is 1 greater than 2 greater than 3 while in the chronotropic response in guinea pig atria the relative order of activity is 1 greater than 3 greater than 2."}
{"id": "PMID:17751", "title": "Cyanoguanidine-thiourea equivalence in the development of the histamine H2-receptor antagonist, cimetidine.", "content": "In the histamine H2-receptor antagonist metiamide (2a) isosteric replacement of thione sulfur (=S) by carbonyl oxygen (=O) or imino nitrogen (=NH) affords the urea 2c and guanidine 2d which are antagonists of decreased potency. The guanidine is very basic and at physiological pH is completely protonated. However, introduction of strongly electronegative substituents into the guanidine group reduces basicity and gives potent H2-receptor antagonists, viz. the cyanoguanidine 2b (cimetidine, \"Tagamet\") and nitroguanidine 2e. A correspondence between the activity of thioureas and cyanoguanidines is demonstrated for a series of structures 1-4. The close correspondence between cyanoguanidine and thiourea in many physicochemical properties and the pharmacological equivalence of these groups in H2-receptor antagonists leads to the description of cyanoguanidine and thiourea as bioisosteres. Acid hydrolysis of the cyanoguanidine 2b yields the carbamoylguanidine 2f at ambient temperatures and the guanidine 2d at elevated temperatures. Cimetidine is slightly more active than metiamide in vivo as an inhibitor of histamine-stimulated gastric acid secretion and has clinical use in the treatment of peptic ulcer and associated gastrointestinal disorders.", "contents": "Cyanoguanidine-thiourea equivalence in the development of the histamine H2-receptor antagonist, cimetidine. In the histamine H2-receptor antagonist metiamide (2a) isosteric replacement of thione sulfur (=S) by carbonyl oxygen (=O) or imino nitrogen (=NH) affords the urea 2c and guanidine 2d which are antagonists of decreased potency. The guanidine is very basic and at physiological pH is completely protonated. However, introduction of strongly electronegative substituents into the guanidine group reduces basicity and gives potent H2-receptor antagonists, viz. the cyanoguanidine 2b (cimetidine, \"Tagamet\") and nitroguanidine 2e. A correspondence between the activity of thioureas and cyanoguanidines is demonstrated for a series of structures 1-4. The close correspondence between cyanoguanidine and thiourea in many physicochemical properties and the pharmacological equivalence of these groups in H2-receptor antagonists leads to the description of cyanoguanidine and thiourea as bioisosteres. Acid hydrolysis of the cyanoguanidine 2b yields the carbamoylguanidine 2f at ambient temperatures and the guanidine 2d at elevated temperatures. Cimetidine is slightly more active than metiamide in vivo as an inhibitor of histamine-stimulated gastric acid secretion and has clinical use in the treatment of peptic ulcer and associated gastrointestinal disorders."}
{"id": "PMID:17752", "title": "beta-Adrenoceptor blocking activity of halogenated thienylethanolamine derivatives.", "content": "The synthesis of a number of ring-halogenated N-isopropyl- and N-tert-butyl-2-amino-1-(2-thienyl)ethanols has been carried out in order to ascertain the influence of chloro or bromo substitution at the thiophene moiety on their blocking beta-adrenoceptor activity. It was found that chloro- and bromo-substituted compounds exhibited a similar activity. Monohalo substitution at positions C4 or C5 of the thiophene ring resulted in comparable blocking potency, whereas C3 halo-substituted compounds were practically devoid of activity. The highest activity in these series was observed with compounds dihalogenated at C4 and C5, their effect on myocardial beta-receptors being comparable to that of propranolol.", "contents": "beta-Adrenoceptor blocking activity of halogenated thienylethanolamine derivatives. The synthesis of a number of ring-halogenated N-isopropyl- and N-tert-butyl-2-amino-1-(2-thienyl)ethanols has been carried out in order to ascertain the influence of chloro or bromo substitution at the thiophene moiety on their blocking beta-adrenoceptor activity. It was found that chloro- and bromo-substituted compounds exhibited a similar activity. Monohalo substitution at positions C4 or C5 of the thiophene ring resulted in comparable blocking potency, whereas C3 halo-substituted compounds were practically devoid of activity. The highest activity in these series was observed with compounds dihalogenated at C4 and C5, their effect on myocardial beta-receptors being comparable to that of propranolol."}
{"id": "PMID:17753", "title": "B/C-cis- and -trans-1,3,4,9,10,10a-Hexahydro-2H-10,4a-methanoiminoethanophenanthrene (homo- and homoisomorphinan) derivatives as analgesics.", "content": "N-Alkyl derivatives of B/C-cis- and B/C-trans-6-hydroxy-1,3,4,9,10,10a-hexahydro-2H-10,4a-methanoimino-ethanophenanthrene have been prepared. The analgesic potency and physical dependence capacity of these compounds were determined. The N-methyl derivatives were analgesically equipotent with morphine. None of these compounds except the N-methyl-B/C-trans isomer 2b suppressed or precipitated the abstinence syndrome. Compound 2b was a narcotic agonist. The N-methyl-B/C-cis compound 2a appears to warrant further examination for its potential as a potent analgesic having no physical dependence liability.", "contents": "B/C-cis- and -trans-1,3,4,9,10,10a-Hexahydro-2H-10,4a-methanoiminoethanophenanthrene (homo- and homoisomorphinan) derivatives as analgesics. N-Alkyl derivatives of B/C-cis- and B/C-trans-6-hydroxy-1,3,4,9,10,10a-hexahydro-2H-10,4a-methanoimino-ethanophenanthrene have been prepared. The analgesic potency and physical dependence capacity of these compounds were determined. The N-methyl derivatives were analgesically equipotent with morphine. None of these compounds except the N-methyl-B/C-trans isomer 2b suppressed or precipitated the abstinence syndrome. Compound 2b was a narcotic agonist. The N-methyl-B/C-cis compound 2a appears to warrant further examination for its potential as a potent analgesic having no physical dependence liability."}
{"id": "PMID:17756", "title": "Retro-umbilical ectopic testicle: report of a case.", "content": "A case of a retro-umbilical ectopic testicle in a 13-year-old cryptorchid boy is reported. To our knowledge this has not been reported previously. There is no definite explanation for this highly aberrant ectopia. During the neonatal period the boy had an umbilical suppuration that required drainage. This may offer a possible explanation since the consequent healing process could have pulled the peritoneum upwards, dragging the testicle with it. Despite the high position of this testicle (and previous operation on the other side) it was easy to cross over both testes successfully to the heterolateral scrotum.", "contents": "Retro-umbilical ectopic testicle: report of a case. A case of a retro-umbilical ectopic testicle in a 13-year-old cryptorchid boy is reported. To our knowledge this has not been reported previously. There is no definite explanation for this highly aberrant ectopia. During the neonatal period the boy had an umbilical suppuration that required drainage. This may offer a possible explanation since the consequent healing process could have pulled the peritoneum upwards, dragging the testicle with it. Despite the high position of this testicle (and previous operation on the other side) it was easy to cross over both testes successfully to the heterolateral scrotum."}
{"id": "PMID:17757", "title": "Complications of autonomic dysreflexia.", "content": "Autonomic dysreflexia can be a life-threatening problem if not promptly recognized and treated. Since the most common cause is bladder distension it is essential that the urologist be familiar with this syndrome. Several patients with serious complications owing to autonomic dysreflexia, including 1 mortality, are presented. The complications of autonomic dysreflexia result from a sudden marked rise in blood pressure, which may be severe enough to rupture single or multiple cerebral blood vessels or lead to a considerable increase in intracranial pressure. The neurophysiology, clinical features and therapeutic measures are discussed.", "contents": "Complications of autonomic dysreflexia. Autonomic dysreflexia can be a life-threatening problem if not promptly recognized and treated. Since the most common cause is bladder distension it is essential that the urologist be familiar with this syndrome. Several patients with serious complications owing to autonomic dysreflexia, including 1 mortality, are presented. The complications of autonomic dysreflexia result from a sudden marked rise in blood pressure, which may be severe enough to rupture single or multiple cerebral blood vessels or lead to a considerable increase in intracranial pressure. The neurophysiology, clinical features and therapeutic measures are discussed."}
{"id": "PMID:17760", "title": "High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants.", "content": "Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants.", "contents": "High-flow total body perfusion with severe hemodilution and normothermia in infants weighing less than 10 kg--safe limits of hemodilution in cardiopulmonary bypass in infants. Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants."}
{"id": "PMID:17762", "title": "Potassium and intracellular pH.", "content": "Recent work has clarified some of the complex interrelationships between cell pH and potassium. These studies have been limited by the techniques available for accurately measuring cell pH. At present it is obvious that intracellular pH is a major regulator of the cellular potassium concentration, but the precise relationship between these two is still uncertain. It has become increasingly clear, however, that no simple relationship exists between the intracellular to extracellular hydrogen ion and potassium ion ratios. Many experiments do demonstrate that the extracellular metabolic alkalosis of potassium depletion is accompanied by a decrease in skeletal muscle pH in rat, rabbit, and probably dog. The response of cardiac and renal tubular cell pH to potassium depletion is less clear, although most evidence indicates that there is also a reduction in the pH of these tissues. This effect on cell pH appears to be independent of chloride. By contrast, hyperkalemia seems to raise muscle cell pH at the same time it induces an extracellular metabolic acidosis. The metabolic and physiologic consequences of potassium-induced alterations in cell pH have yet to be fully elucidated.", "contents": "Potassium and intracellular pH. Recent work has clarified some of the complex interrelationships between cell pH and potassium. These studies have been limited by the techniques available for accurately measuring cell pH. At present it is obvious that intracellular pH is a major regulator of the cellular potassium concentration, but the precise relationship between these two is still uncertain. It has become increasingly clear, however, that no simple relationship exists between the intracellular to extracellular hydrogen ion and potassium ion ratios. Many experiments do demonstrate that the extracellular metabolic alkalosis of potassium depletion is accompanied by a decrease in skeletal muscle pH in rat, rabbit, and probably dog. The response of cardiac and renal tubular cell pH to potassium depletion is less clear, although most evidence indicates that there is also a reduction in the pH of these tissues. This effect on cell pH appears to be independent of chloride. By contrast, hyperkalemia seems to raise muscle cell pH at the same time it induces an extracellular metabolic acidosis. The metabolic and physiologic consequences of potassium-induced alterations in cell pH have yet to be fully elucidated."}
{"id": "PMID:17763", "title": "Relationship of renal ammonia production and potassium homeostasis.", "content": "Renal ammonia production appears to be intimately related to potassium homeostasis, and the two may comprise the components of a closed loop regulatory system. Studies with both intact organisms and in vitro systems indicate that potassium depletion stimulates and chronic potassium-loading suppresses renal ammonia production. An increase in ammoniagenesis has been shown to decrease potassium excretion. These observations suggest that changes in potassium modulate ammonia production, which in turn maintains hydrogen ion homeostasis and influences potassium excretion. Potassium depletion increases rat renal cortical ammonia production by altering metabolism in fashion identical to metabolic acidosis, but there is no convincing evidence that both processes are mediated by similar changes in either cellular hydrogen ion or potassium concentration. By contrast, potassium-loading, which depresses ammonia production, appears to affect primarily the outer medulla, a region that is not influenced by potassium depletion. Thus, potassium-loading apparently affects different portions of the renal tubule than depletion does, but the specific mechanism and physiologic significance of the different sites of action is unknown.", "contents": "Relationship of renal ammonia production and potassium homeostasis. Renal ammonia production appears to be intimately related to potassium homeostasis, and the two may comprise the components of a closed loop regulatory system. Studies with both intact organisms and in vitro systems indicate that potassium depletion stimulates and chronic potassium-loading suppresses renal ammonia production. An increase in ammoniagenesis has been shown to decrease potassium excretion. These observations suggest that changes in potassium modulate ammonia production, which in turn maintains hydrogen ion homeostasis and influences potassium excretion. Potassium depletion increases rat renal cortical ammonia production by altering metabolism in fashion identical to metabolic acidosis, but there is no convincing evidence that both processes are mediated by similar changes in either cellular hydrogen ion or potassium concentration. By contrast, potassium-loading, which depresses ammonia production, appears to affect primarily the outer medulla, a region that is not influenced by potassium depletion. Thus, potassium-loading apparently affects different portions of the renal tubule than depletion does, but the specific mechanism and physiologic significance of the different sites of action is unknown."}
{"id": "PMID:17766", "title": "Side effects and contraindications of beta-receptor blocking agents.", "content": "Unwanted effects of beta-receptor blocking agents can be divided into three categories: 1. Those arising specifically from the pharmacologic, i.e., beta-blocking action. 2. Side effects not directly (or not with certainty) related to beta-blockade. 3. Adverse and potentially specific reactions to individual beta-blocking agents. Category 1 covers the majority of adverse effects (heart failure, severe bradycardia and hypotension, arterial insufficiency, increased airways resistance, gastrointestinal symptoms, hypoglycemia). These can largely be avoided by proper selection and preparation of patients. Category 2 covers cutaneous reactions (rashes, alopecia, pruritus), purpura (thrombocytopenic and nonthrombocytopenic) etc. as well as side effects attributable to the central nervous system (antianxiety effects, nightmares etc.). In the third category the \"oculo-cutaneous syndrome\" associated with practolol is discussed.", "contents": "Side effects and contraindications of beta-receptor blocking agents. Unwanted effects of beta-receptor blocking agents can be divided into three categories: 1. Those arising specifically from the pharmacologic, i.e., beta-blocking action. 2. Side effects not directly (or not with certainty) related to beta-blockade. 3. Adverse and potentially specific reactions to individual beta-blocking agents. Category 1 covers the majority of adverse effects (heart failure, severe bradycardia and hypotension, arterial insufficiency, increased airways resistance, gastrointestinal symptoms, hypoglycemia). These can largely be avoided by proper selection and preparation of patients. Category 2 covers cutaneous reactions (rashes, alopecia, pruritus), purpura (thrombocytopenic and nonthrombocytopenic) etc. as well as side effects attributable to the central nervous system (antianxiety effects, nightmares etc.). In the third category the \"oculo-cutaneous syndrome\" associated with practolol is discussed."}
{"id": "PMID:17770", "title": "[Psychopharmacology in aviation and astronautics].", "content": "Flights aboard modern vehicles are associated with high nervous-emotional and physical stresses. This may induce depletion of reserve capabilities, development of fatigue and, consequently, reduction of work capacity of crewmembers. The paper discusses approaches and results of the use of drugs by pilots and cosmonauts in order to alleviate their fatigue and emotional stress. It gives indications and contraindications for the adminstration of stimulants and tranquilizers. On the basis of a comprehensive analysis of the literature data and their own findings, the authors draw the conclusion that the use of stimulants and anxiolytics may increase the level of reliability and performance of air- and spacecraft pilots during programmed and, particularly, contigent situations of the flight.", "contents": "[Psychopharmacology in aviation and astronautics]. Flights aboard modern vehicles are associated with high nervous-emotional and physical stresses. This may induce depletion of reserve capabilities, development of fatigue and, consequently, reduction of work capacity of crewmembers. The paper discusses approaches and results of the use of drugs by pilots and cosmonauts in order to alleviate their fatigue and emotional stress. It gives indications and contraindications for the adminstration of stimulants and tranquilizers. On the basis of a comprehensive analysis of the literature data and their own findings, the authors draw the conclusion that the use of stimulants and anxiolytics may increase the level of reliability and performance of air- and spacecraft pilots during programmed and, particularly, contigent situations of the flight."}
{"id": "PMID:17771", "title": "[Psychoneurological requirements in evaluating the functional state of cosmonauts in flight].", "content": "Selection and training of experts-psychoneurologists to be included into a team of operational medical monitoring are described. In regards to the capacity for synonymic paraphrasing, the conditions required for stability of individual opinions and their coincidence in different people are discussed. The capacity refers to the choice of the most suitable word among a number of synonyms. On this basis it is recommended to use similarity problems in appraising the function of an expert who involves verbal description of various events.", "contents": "[Psychoneurological requirements in evaluating the functional state of cosmonauts in flight]. Selection and training of experts-psychoneurologists to be included into a team of operational medical monitoring are described. In regards to the capacity for synonymic paraphrasing, the conditions required for stability of individual opinions and their coincidence in different people are discussed. The capacity refers to the choice of the most suitable word among a number of synonyms. On this basis it is recommended to use similarity problems in appraising the function of an expert who involves verbal description of various events."}
{"id": "PMID:17772", "title": "[Dynamic control of the atmospheric parameters of spacecraft].", "content": "On the basis of experimental data a mathematical model of relationships between physiological parameters, oxygen content in the atmosphere and exercises has been developed. Using the model, it has been demonstrated that circulation and respiration reactions to exercises can be optimized by increasing the partial pressure of oxygen as related to the exercise level. A probable law of the dynamic and physiologically  optimal control of the oxygen content in the space cabin atmosphere has been advanced. In cases of an uncontrolled decrease of PO2 the oxygen supply of crewmembers can be optimized by the dynamic control of the ambient CO2 content.", "contents": "[Dynamic control of the atmospheric parameters of spacecraft]. On the basis of experimental data a mathematical model of relationships between physiological parameters, oxygen content in the atmosphere and exercises has been developed. Using the model, it has been demonstrated that circulation and respiration reactions to exercises can be optimized by increasing the partial pressure of oxygen as related to the exercise level. A probable law of the dynamic and physiologically  optimal control of the oxygen content in the space cabin atmosphere has been advanced. In cases of an uncontrolled decrease of PO2 the oxygen supply of crewmembers can be optimized by the dynamic control of the ambient CO2 content."}
{"id": "PMID:17773", "title": "[Electrolyte content in the blood of animals and potassium ion transport in the erythrocytes under the action of a constant magnetic field].", "content": "The content of potassium and sodium ions in the blood and plasma of rats exposed to constant magnetic fileds (CMF) of 1000 and 4500 oersted for varying time was studied. The transport of potassium ions through membranes of red blood cells was examined in in bitro experiments using a CMF of 4500 oersted. An exposure of animals to a CMF of 1000 oersted for 1 and 24 hours did not produce significant changes in the potassium and sodium content in blood. An exposure of animals to a CMF of 4500 oersted induced certain changes in the electrolyte composition of the blood. During an hour exposure the most distinct changes were an increase in the potassium concentration in plasma and its decrease in blood. During a 3-hour exposure the most marked change was a decrease in the sodium content in blood. Repeated and prolonged chronic exposure did not bring about summation of the effects. The exposure did not influence the transport of potassium ions. The exposure did not affect the pH and hematokrit values of the blood.", "contents": "[Electrolyte content in the blood of animals and potassium ion transport in the erythrocytes under the action of a constant magnetic field]. The content of potassium and sodium ions in the blood and plasma of rats exposed to constant magnetic fileds (CMF) of 1000 and 4500 oersted for varying time was studied. The transport of potassium ions through membranes of red blood cells was examined in in bitro experiments using a CMF of 4500 oersted. An exposure of animals to a CMF of 1000 oersted for 1 and 24 hours did not produce significant changes in the potassium and sodium content in blood. An exposure of animals to a CMF of 4500 oersted induced certain changes in the electrolyte composition of the blood. During an hour exposure the most distinct changes were an increase in the potassium concentration in plasma and its decrease in blood. During a 3-hour exposure the most marked change was a decrease in the sodium content in blood. Repeated and prolonged chronic exposure did not bring about summation of the effects. The exposure did not influence the transport of potassium ions. The exposure did not affect the pH and hematokrit values of the blood."}
{"id": "PMID:17774", "title": "[Study of the nature of the associated microflora in the prolonged substrateless cultivation of beet plants].", "content": "The purpose of the present investigation was to study variations in the population density of microorganisms, their qualitative and quantitative composition during substrate-free cultivation of beats. The results obtained show that the microbial number in the nutrient solution increased by the time of intensive growth of beats and decreased by the time of harvesting. The number of root microorganisms was much greater than the total number of microorganisms in the nutrient solution. Oligonitrophils and nitrogen fixing bacteria were found in the solution. This may be associated with a transient decrease of nitrogen in the solution. The number of ammonifiers and denitrifiers in the solution increased significantly by the end  of plant vegetation; the amount of denitrifiers inhabiting the roots decreased during vegetation and that of ammonifiers increased. In the middle of vegetation cellulose decomposing aerobes appeared; this might occur since root hairs began to die off. By the end of vegetation an insignificant amount of fungi was also found. Nitrifying and spore-forming microorganisms were not detected. The identification of predominant microbial species showed them to be bacteria of the genera Pseudomonas and Mycobacterium. Besides, microorganisms of the genera Bacterium, Micrococcus, Mycococcus, Chromobacterium and Pseudobacterium also occurred.", "contents": "[Study of the nature of the associated microflora in the prolonged substrateless cultivation of beet plants]. The purpose of the present investigation was to study variations in the population density of microorganisms, their qualitative and quantitative composition during substrate-free cultivation of beats. The results obtained show that the microbial number in the nutrient solution increased by the time of intensive growth of beats and decreased by the time of harvesting. The number of root microorganisms was much greater than the total number of microorganisms in the nutrient solution. Oligonitrophils and nitrogen fixing bacteria were found in the solution. This may be associated with a transient decrease of nitrogen in the solution. The number of ammonifiers and denitrifiers in the solution increased significantly by the end  of plant vegetation; the amount of denitrifiers inhabiting the roots decreased during vegetation and that of ammonifiers increased. In the middle of vegetation cellulose decomposing aerobes appeared; this might occur since root hairs began to die off. By the end of vegetation an insignificant amount of fungi was also found. Nitrifying and spore-forming microorganisms were not detected. The identification of predominant microbial species showed them to be bacteria of the genera Pseudomonas and Mycobacterium. Besides, microorganisms of the genera Bacterium, Micrococcus, Mycococcus, Chromobacterium and Pseudobacterium also occurred."}
{"id": "PMID:17779", "title": "[The use of Goetze cerclage in the treatment of tibial fractures].", "content": "On the basis of the authors' experiences and the data of the available literature Goetze's cerclage in the treatment of tibia fractures is discussed--as far as the authors know, this is the first report of this method in the Hungarian literature. On the basis of the authors' material, the method is very useful for the treatment of the long, spiral and oblique fractures of the leg.", "contents": "[The use of Goetze cerclage in the treatment of tibial fractures]. On the basis of the authors' experiences and the data of the available literature Goetze's cerclage in the treatment of tibia fractures is discussed--as far as the authors know, this is the first report of this method in the Hungarian literature. On the basis of the authors' material, the method is very useful for the treatment of the long, spiral and oblique fractures of the leg."}
{"id": "PMID:17781", "title": "[Diabetic osteoarthropathy of rare localization].", "content": "The typical location of diabetic osteoarthropathy is the foot. Involvement of other joints is rare. In the case treated by the author, the osteoarthropathy of the ankle and knee joints presented at the same time. The process healed in the ankle joint by grave deformity and arthrosis deformans resulted in the knee joint. If arthrosis appears in an unusual location, it is worth while to look for diabetes.", "contents": "[Diabetic osteoarthropathy of rare localization]. The typical location of diabetic osteoarthropathy is the foot. Involvement of other joints is rare. In the case treated by the author, the osteoarthropathy of the ankle and knee joints presented at the same time. The process healed in the ankle joint by grave deformity and arthrosis deformans resulted in the knee joint. If arthrosis appears in an unusual location, it is worth while to look for diabetes."}
{"id": "PMID:17782", "title": "[Thoracic injury and fat embolism].", "content": "The authors state that fat embolism occurs rather frequently following thoracic injuries. It is difficult to make a diagnosis because of the complexity of the symptoms. The correct evaluation of the characteristic clinical and laboratory signs arising after a period free of symptoms is essential. The authors outline the brief case history of a successfully treated patient, who recovered, owing to the use of the respirator in the intensive care unit.", "contents": "[Thoracic injury and fat embolism]. The authors state that fat embolism occurs rather frequently following thoracic injuries. It is difficult to make a diagnosis because of the complexity of the symptoms. The correct evaluation of the characteristic clinical and laboratory signs arising after a period free of symptoms is essential. The authors outline the brief case history of a successfully treated patient, who recovered, owing to the use of the respirator in the intensive care unit."}
{"id": "PMID:17783", "title": "[Vascular injury associated with shoulder luxation].", "content": "The author reports on the rupture of subscapular artery that followed the reduction of an anterior dislocation of the shoulder joint. On this occasion, vascular injuries associated with shoulder joint dislocation, their diagnosis and treatment is discussed in the article. The aim of the author was to remind the reader to a complication of our everyday activity. He wants to call attention to the importance of gentle manipulation and the careful observation of the circulation after reduction.", "contents": "[Vascular injury associated with shoulder luxation]. The author reports on the rupture of subscapular artery that followed the reduction of an anterior dislocation of the shoulder joint. On this occasion, vascular injuries associated with shoulder joint dislocation, their diagnosis and treatment is discussed in the article. The aim of the author was to remind the reader to a complication of our everyday activity. He wants to call attention to the importance of gentle manipulation and the careful observation of the circulation after reduction."}
{"id": "PMID:17784", "title": "[15 years of anesthesia in hand surgery].", "content": "The authors give an account on their experiences in the anaesthesy on the hand area. Methods used during a 15 year period are reported, different sorts of narcosis and the intravenous regional anaesthesy is discussed. Advantages and disadvantages of the particular methods are outlined.", "contents": "[15 years of anesthesia in hand surgery]. The authors give an account on their experiences in the anaesthesy on the hand area. Methods used during a 15 year period are reported, different sorts of narcosis and the intravenous regional anaesthesy is discussed. Advantages and disadvantages of the particular methods are outlined."}
{"id": "PMID:17787", "title": "[Early surgery of the soft tissues in congenital clubfoot].", "content": "The role and position of early complete operative procedures on the soft tissues in the treatment of the congenital club foot is discussed in the article. The authors report on the operative indications in principles and in their own practice. Closed and operative treatment are not contradictory but complementary terms. The aim of the operative treatment is to bring all residual contractures following conservative treatment to an end. It must be done by relatively minimal intervention on the soft tissues and as early as possible. Thus the proper development of the foot and the prevention of bone deformation can be attained.", "contents": "[Early surgery of the soft tissues in congenital clubfoot]. The role and position of early complete operative procedures on the soft tissues in the treatment of the congenital club foot is discussed in the article. The authors report on the operative indications in principles and in their own practice. Closed and operative treatment are not contradictory but complementary terms. The aim of the operative treatment is to bring all residual contractures following conservative treatment to an end. It must be done by relatively minimal intervention on the soft tissues and as early as possible. Thus the proper development of the foot and the prevention of bone deformation can be attained."}
{"id": "PMID:17788", "title": "[Management of mass injuries in railway accidents].", "content": "Authors write up the experiences they gained at repeated train accidents on the same section of railway line. The circumstances of the two accidents are evaluated and analysed. The experiences they obtained at the first accident were put to use the second time. The authors stress that the growing number of mass accidents makes it necessary to prepare an alarm and provision plan for every institution.", "contents": "[Management of mass injuries in railway accidents]. Authors write up the experiences they gained at repeated train accidents on the same section of railway line. The circumstances of the two accidents are evaluated and analysed. The experiences they obtained at the first accident were put to use the second time. The authors stress that the growing number of mass accidents makes it necessary to prepare an alarm and provision plan for every institution."}
{"id": "PMID:17790", "title": "[Surgical management of thoracic and thoraco-abdominal injuries].", "content": "From 1970 to 1974 407 patients with thoracic injuries have been treated by the authors in the 2nd Surgical and Thoracic Surgical Department of the \"J\u00e1nos\" Hospital, Budapest--out of them 190 patients were classified as severely injured. The material and the operative technique in isolated thoracal and combined thoracal-abdominal injuries are discussed. The importance of the operative stabilization of the thoracic wall is emphasized and fixation of the thoracic wall by means of pericostal sutures is advocated, if because of the intrathoracal injury--just the same--thoracotomy is to be performed. On the basis of their experiences and because of the risk of late complications and of residues impairing the function in certain types of the thoracal injuries surgical treatment is advocated by the authors.", "contents": "[Surgical management of thoracic and thoraco-abdominal injuries]. From 1970 to 1974 407 patients with thoracic injuries have been treated by the authors in the 2nd Surgical and Thoracic Surgical Department of the \"J\u00e1nos\" Hospital, Budapest--out of them 190 patients were classified as severely injured. The material and the operative technique in isolated thoracal and combined thoracal-abdominal injuries are discussed. The importance of the operative stabilization of the thoracic wall is emphasized and fixation of the thoracic wall by means of pericostal sutures is advocated, if because of the intrathoracal injury--just the same--thoracotomy is to be performed. On the basis of their experiences and because of the risk of late complications and of residues impairing the function in certain types of the thoracal injuries surgical treatment is advocated by the authors."}
{"id": "PMID:17791", "title": "[Fracture-dislocation of the hip joint. II. Central luxation].", "content": "64 cases of central luxation are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. It has been stated by the authors that because of the severity of the injury and the age of the injured patients surgical intervention may be performed even in case of greater dislocation but rarely. The result of the conservative treatment is in the case of congruency of the loading surface satisfactory, but it is even in the case of incongruency generally better than it may be supposed on the basis of the roentgenogram. For the prevention of later occurring severe arthrosis the importance of the rehabilitation is emphasized by the authors.", "contents": "[Fracture-dislocation of the hip joint. II. Central luxation]. 64 cases of central luxation are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. It has been stated by the authors that because of the severity of the injury and the age of the injured patients surgical intervention may be performed even in case of greater dislocation but rarely. The result of the conservative treatment is in the case of congruency of the loading surface satisfactory, but it is even in the case of incongruency generally better than it may be supposed on the basis of the roentgenogram. For the prevention of later occurring severe arthrosis the importance of the rehabilitation is emphasized by the authors."}
{"id": "PMID:17792", "title": "[Pathological sagittal shifting of vertebral bodies].", "content": "The results of the lumbar spine examinations performed in one year and a half are evaluated by the authors. The types of the sagittal positional changes of the vertebral bodies are discussed in detail. The importance of the functionally centrated and lateral telephotographs in the diagnosis of the antepositional olisthesis and the retropositional retrolisthesis is pointed out, and the indication and the differential diagnostical value of the oblique roentgenograms are dealt with.", "contents": "[Pathological sagittal shifting of vertebral bodies]. The results of the lumbar spine examinations performed in one year and a half are evaluated by the authors. The types of the sagittal positional changes of the vertebral bodies are discussed in detail. The importance of the functionally centrated and lateral telephotographs in the diagnosis of the antepositional olisthesis and the retropositional retrolisthesis is pointed out, and the indication and the differential diagnostical value of the oblique roentgenograms are dealt with."}
{"id": "PMID:17794", "title": "Drug utilization review in an HMO. I. Introduction and examples of methodology.", "content": "An experimental drug utilization review program was developed for a health maintenance organization (HMO). The objectives of the program were to develop and implement an ongoing mechanism for reviewing drug use using criteria based on the scientific literature, and to evaluate the effect of the drug use review program on physician precribing patterns. Seven therapeutic categories of drugs, accounting for over 65 per cent of prescribing, were selected and criteria developed for their use. The drug use review prcedure is described briefly. The evaluation of the drug use review program is based on a comparison of rates of prescription use for specific therapeutic categories before and after the criteria were ceveloped and approved. As an example, data for the antihistamine therapeutic category are presented. Criteria for prescribing antihistamines suggested restricting use of combination cold preparations and refraiming from antihistamine use in viral upper respiratory tract infections. After the criteria were adopted, prescribing of antihistamines for viral URIs declined, particularly in pediatrics. In general, prescribing of combination antihistamine preparations did not change; where one combination preparation was deleted from the formulary, prescribers appeared to substitute another combination preparation.", "contents": "Drug utilization review in an HMO. I. Introduction and examples of methodology. An experimental drug utilization review program was developed for a health maintenance organization (HMO). The objectives of the program were to develop and implement an ongoing mechanism for reviewing drug use using criteria based on the scientific literature, and to evaluate the effect of the drug use review program on physician precribing patterns. Seven therapeutic categories of drugs, accounting for over 65 per cent of prescribing, were selected and criteria developed for their use. The drug use review prcedure is described briefly. The evaluation of the drug use review program is based on a comparison of rates of prescription use for specific therapeutic categories before and after the criteria were ceveloped and approved. As an example, data for the antihistamine therapeutic category are presented. Criteria for prescribing antihistamines suggested restricting use of combination cold preparations and refraiming from antihistamine use in viral upper respiratory tract infections. After the criteria were adopted, prescribing of antihistamines for viral URIs declined, particularly in pediatrics. In general, prescribing of combination antihistamine preparations did not change; where one combination preparation was deleted from the formulary, prescribers appeared to substitute another combination preparation."}
{"id": "PMID:17795", "title": "[Effects and side effects of oral drugs used in common cold (author's transl)].", "content": "A report about effects and side effects of common cold remedies that are taken orally is presented. There are advantages and disadvantages in the use of either locally administered nose drops or orally taken cold remedies, which are compared to each other from the pharmacological point of view. Based on the experience of a great toxicological center and a pediatric clinic, the clinical symptoms of poisoning as a result of accidental ingestion are described and contraindications are pointed out. It is concluded that, especially in children, the dosage of both oral and local drugs should not exceed the recommended amount.", "contents": "[Effects and side effects of oral drugs used in common cold (author's transl)]. A report about effects and side effects of common cold remedies that are taken orally is presented. There are advantages and disadvantages in the use of either locally administered nose drops or orally taken cold remedies, which are compared to each other from the pharmacological point of view. Based on the experience of a great toxicological center and a pediatric clinic, the clinical symptoms of poisoning as a result of accidental ingestion are described and contraindications are pointed out. It is concluded that, especially in children, the dosage of both oral and local drugs should not exceed the recommended amount."}
{"id": "PMID:17808", "title": "Alkaline ribonuclease inhibitor in human thyroid.", "content": "Thyroids of goitrogen-treated rats contain increased amounts of a protein inhibitor of ribonuclease activity at pH greater than 7 (alkaline ribonuclease inhibitor, ARI). We report here that thyroids from hyperthyroid patients contain more ARI than normal human thyroids. This increase parallels RNA concentration. The inhibitor is heat labile, inactivated by sulfhydryl blocking agents, and has a molecular weight near 50, 000 daltons. ARI is quantitated by its activity against bovine pancreatic RNase, but it also inhibits human thyroid RNase. Analyses of a solitary toxic nodule and its surrounding suppressed tissue confirm in tissues from a single patient our results in tissue from numbers of thyrotoxic and euthyroid individuals and decrease the likelihood that changes are induced by antithyroid medication. A possible regulatory role for ARI is suggested.", "contents": "Alkaline ribonuclease inhibitor in human thyroid. Thyroids of goitrogen-treated rats contain increased amounts of a protein inhibitor of ribonuclease activity at pH greater than 7 (alkaline ribonuclease inhibitor, ARI). We report here that thyroids from hyperthyroid patients contain more ARI than normal human thyroids. This increase parallels RNA concentration. The inhibitor is heat labile, inactivated by sulfhydryl blocking agents, and has a molecular weight near 50, 000 daltons. ARI is quantitated by its activity against bovine pancreatic RNase, but it also inhibits human thyroid RNase. Analyses of a solitary toxic nodule and its surrounding suppressed tissue confirm in tissues from a single patient our results in tissue from numbers of thyrotoxic and euthyroid individuals and decrease the likelihood that changes are induced by antithyroid medication. A possible regulatory role for ARI is suggested."}
{"id": "PMID:17809", "title": "Alcohol: its effect on the kidney.", "content": "The effect of ethanol feeding on renal function, gross and microscopic morphology, and constituent content was determined in alcohol-fed rats and compared to similar studies in isocalorically fed animals ingesting the same diet except that dextrimaltose was isocalorically substituted for ethanol. Alcohol-fed animals have significantly reduced renal function and interstitial edema compared to their isocaloric controls. When renal mass and renal constituent analysis were normalized for body weight, alcohol-fed animals were found to have renal hypertrophy characterized by significantly increased absolute amounts of protein (p less than 0.01), fat (p less than 0.01), and water (p less than 0.01). All of these constituents increased in proportion to their percentage of total renal mass in control animals. In contrast, DNA content per kidney was similar for alcohol and isocalorically fed animals.", "contents": "Alcohol: its effect on the kidney. The effect of ethanol feeding on renal function, gross and microscopic morphology, and constituent content was determined in alcohol-fed rats and compared to similar studies in isocalorically fed animals ingesting the same diet except that dextrimaltose was isocalorically substituted for ethanol. Alcohol-fed animals have significantly reduced renal function and interstitial edema compared to their isocaloric controls. When renal mass and renal constituent analysis were normalized for body weight, alcohol-fed animals were found to have renal hypertrophy characterized by significantly increased absolute amounts of protein (p less than 0.01), fat (p less than 0.01), and water (p less than 0.01). All of these constituents increased in proportion to their percentage of total renal mass in control animals. In contrast, DNA content per kidney was similar for alcohol and isocalorically fed animals."}
{"id": "PMID:17805", "title": "Lophyrotomin, a new toxic octapeptide from the larvae of sawfly, Lophyrotoma interrupta.", "content": "Lophyrotomin, a new toxic octapeptide, has been isolated from sawfly (Lophyrotoma interrupta) larvae using solvent extraction, dialysis, adsorption on polyamide, ion exchange chromatography on DEAE cellulose and silica gel G chromatography. On the basis of evidence from chemical methods, pmr and mass spectrometry, a partial structure is proposed. Lophyrotomin has an approximate intraperitoneal LD50 of 2 mg/kg for mice.", "contents": "Lophyrotomin, a new toxic octapeptide from the larvae of sawfly, Lophyrotoma interrupta. Lophyrotomin, a new toxic octapeptide, has been isolated from sawfly (Lophyrotoma interrupta) larvae using solvent extraction, dialysis, adsorption on polyamide, ion exchange chromatography on DEAE cellulose and silica gel G chromatography. On the basis of evidence from chemical methods, pmr and mass spectrometry, a partial structure is proposed. Lophyrotomin has an approximate intraperitoneal LD50 of 2 mg/kg for mice."}
{"id": "PMID:17815", "title": "Heterogeneity of staphylococcal enterotoxin A on isoelectric focusing and disc electrophoresis.", "content": "Heterogeneity of purified staphylococcal enterotoxin A, obtained from a culture supernatant of Staphylococcus aureus, strain 13N-2909, was demonstrated by isoelectric focusing. The toxin was composed of three immunologically identical fractions with isoelectric points of 6.5, 7.0 and approximately 8.0. Heterogeneity of the toxin was also shown by disc electrophoresis. At pH 8.0 and 9.4 two major bands and a faint minor band were observed, while at pH 4.3 only one band was observed. The faster-moving band for the anode in disc electrophoresis at pH 9.4 was found to correspond with the pI 6.5 component from isoelectric focusing, while the slower-moving band corresponded with the pI 7.0 component. From the results of the electrophoretic migration tests of the toxin, the components corresponding to the two major bands found in disc electrophoresis at pH 9.4 were considered to be charge isomers.", "contents": "Heterogeneity of staphylococcal enterotoxin A on isoelectric focusing and disc electrophoresis. Heterogeneity of purified staphylococcal enterotoxin A, obtained from a culture supernatant of Staphylococcus aureus, strain 13N-2909, was demonstrated by isoelectric focusing. The toxin was composed of three immunologically identical fractions with isoelectric points of 6.5, 7.0 and approximately 8.0. Heterogeneity of the toxin was also shown by disc electrophoresis. At pH 8.0 and 9.4 two major bands and a faint minor band were observed, while at pH 4.3 only one band was observed. The faster-moving band for the anode in disc electrophoresis at pH 9.4 was found to correspond with the pI 6.5 component from isoelectric focusing, while the slower-moving band corresponded with the pI 7.0 component. From the results of the electrophoretic migration tests of the toxin, the components corresponding to the two major bands found in disc electrophoresis at pH 9.4 were considered to be charge isomers."}
{"id": "PMID:17816", "title": "An analysis of factors influencing the isolation rate of herpes simplex virus.", "content": "Attempts were made to improve the rate of isolation of herpes simplex virus (HSV) from clinical specimens by minimizing loss of virus infectivity during transportation and employing the most sensitive cells for isolation. Basical analyses using standard strains of type 1 and type 2 HSV indicated that virus titer decrease was marked even at low temperatures in environments free of proteinous stabilizer such as normal serum or tissue extract, negating the generally held concept that HSV is stable in distilled water. YLE (Earle-lactalbumin HYDROLYSATE-YEAST EXTRACT) medium containing 20% inactivated calf serum was determined to be a transport medium of choice, because degradation of suspended virus during storage and freeze-thawing was negligible and loss of virus during Millipore filtration was minimal. Special coating of the membrane could also be obviated by the use of this solution. In a cell susceptibility test using clinical specimens, secondary rabbit kidney (SRK) cells were the most sensitive, showing a quick development of cytopathic effect. Vero and RK-13 cells were the second best, whereas monkey kidney, HeLa and L cells were far less sensitive. A total of 136 specimens from suspected cases, sent by dermatologists, were tested using SRK cells, and 99 strains of type 1 and 15 strains of type 2 HSV were isolated. Excluding one case from which vaccinia virus was isolated, the isolation rate of HSV was 84.4%.", "contents": "An analysis of factors influencing the isolation rate of herpes simplex virus. Attempts were made to improve the rate of isolation of herpes simplex virus (HSV) from clinical specimens by minimizing loss of virus infectivity during transportation and employing the most sensitive cells for isolation. Basical analyses using standard strains of type 1 and type 2 HSV indicated that virus titer decrease was marked even at low temperatures in environments free of proteinous stabilizer such as normal serum or tissue extract, negating the generally held concept that HSV is stable in distilled water. YLE (Earle-lactalbumin HYDROLYSATE-YEAST EXTRACT) medium containing 20% inactivated calf serum was determined to be a transport medium of choice, because degradation of suspended virus during storage and freeze-thawing was negligible and loss of virus during Millipore filtration was minimal. Special coating of the membrane could also be obviated by the use of this solution. In a cell susceptibility test using clinical specimens, secondary rabbit kidney (SRK) cells were the most sensitive, showing a quick development of cytopathic effect. Vero and RK-13 cells were the second best, whereas monkey kidney, HeLa and L cells were far less sensitive. A total of 136 specimens from suspected cases, sent by dermatologists, were tested using SRK cells, and 99 strains of type 1 and 15 strains of type 2 HSV were isolated. Excluding one case from which vaccinia virus was isolated, the isolation rate of HSV was 84.4%."}
{"id": "PMID:17817", "title": "Human infection caused by penicillin-insensitive pneumococci.", "content": "Three cases of infection, including two fatal ones, caused by pneumococci relatively resistant to penicillin are reported. The patients were a 19-year-old New Guinean with fatal multisegmental pneumonia, a 10-week-old Caucasian infant who died suddenly from purulent meningitis, and an Australian Aboriginal child aged two years with bronchiectasis complicated by pneumococcal bacteraemia. The pneumococci isolated (serotypes 6, 16 and 19) showed minimal inhibitory concentrations of penicillin G ranging from 0-1 microgram/ml to 1-0 microgram/ml (resistance ratios five to 50) and were also relatively resistant to penicillin V, methicillin, cloxacillin and cephalosporins.", "contents": "Human infection caused by penicillin-insensitive pneumococci. Three cases of infection, including two fatal ones, caused by pneumococci relatively resistant to penicillin are reported. The patients were a 19-year-old New Guinean with fatal multisegmental pneumonia, a 10-week-old Caucasian infant who died suddenly from purulent meningitis, and an Australian Aboriginal child aged two years with bronchiectasis complicated by pneumococcal bacteraemia. The pneumococci isolated (serotypes 6, 16 and 19) showed minimal inhibitory concentrations of penicillin G ranging from 0-1 microgram/ml to 1-0 microgram/ml (resistance ratios five to 50) and were also relatively resistant to penicillin V, methicillin, cloxacillin and cephalosporins."}
{"id": "PMID:17818", "title": "[Bromureide intoxication with acute renal failure and bilateral deep vein thrombosis (author's transl)].", "content": "A case of bromureide intoxication with 8 gm. of carbromal is described, in which an acute renal failure and bilateral deep vein thromboses occurred. After treatment with heparin and peritoneal dialysis the symptoms regressed completely.", "contents": "[Bromureide intoxication with acute renal failure and bilateral deep vein thrombosis (author's transl)]. A case of bromureide intoxication with 8 gm. of carbromal is described, in which an acute renal failure and bilateral deep vein thromboses occurred. After treatment with heparin and peritoneal dialysis the symptoms regressed completely."}
{"id": "PMID:17826", "title": "In vivo and in vitro studies of nitrate reductase regulation in Asperillus nidulans.", "content": "Induced wildtype cells of A. nidulans rapidly lost NADPH--linked nitrate reductase activity when subjected to carbon and or nitrogen starvation. A constitutive mutant at the regulatory gene for nitrate reductase, nir Ac 1, rapidly lost nitrate reductase activity upon carbon starvation. This loss of activity is thought to be due to a decrease in the NADPH concentration in the cells. Cell free extracts from wildtype cells grown in the presence of nitrate, rapidly lost their nitrate reductase activity when incubated at 25 degrees C. NADPH prevented this loss of activity. Wildtype cells grown in the presence of nitrate and urea have a higher initial NADPH:NADP+ ratio and cell free extracts from such cells lost their nitrate reductase activity slower than extracts of cells grown with nitrate alone. The Pentose Phosphate Pathway mutant, pppB-1, had a lower NADPH concentration compared with the wildtype grown under the same conditions and cell free extracts lost their nitrate reductase activity more rapidly than the wildtype. Cell free extracts of nirAc-1 and a non-inducible mutant for nitrate reductase, nirA- -14, upon incubation lost little of their nitrate reductase activity.", "contents": "In vivo and in vitro studies of nitrate reductase regulation in Asperillus nidulans. Induced wildtype cells of A. nidulans rapidly lost NADPH--linked nitrate reductase activity when subjected to carbon and or nitrogen starvation. A constitutive mutant at the regulatory gene for nitrate reductase, nir Ac 1, rapidly lost nitrate reductase activity upon carbon starvation. This loss of activity is thought to be due to a decrease in the NADPH concentration in the cells. Cell free extracts from wildtype cells grown in the presence of nitrate, rapidly lost their nitrate reductase activity when incubated at 25 degrees C. NADPH prevented this loss of activity. Wildtype cells grown in the presence of nitrate and urea have a higher initial NADPH:NADP+ ratio and cell free extracts from such cells lost their nitrate reductase activity slower than extracts of cells grown with nitrate alone. The Pentose Phosphate Pathway mutant, pppB-1, had a lower NADPH concentration compared with the wildtype grown under the same conditions and cell free extracts lost their nitrate reductase activity more rapidly than the wildtype. Cell free extracts of nirAc-1 and a non-inducible mutant for nitrate reductase, nirA- -14, upon incubation lost little of their nitrate reductase activity."}
{"id": "PMID:17832", "title": "Mutagenicity of 22 N-nitrosamides and related compounds for Salmonella typhimurium TA1535.", "content": "Twenty-two N-nitrosamides and related compounds, including 14 nitrosoureas, 5 nitrosocarbamates, and one nitrosocyanamide, were tested at various concentrations for mutagenic activity towards Salmonella typhimurium TA1535 without the use of microsomes. The ether-water partition coefficient, solubility in water, and half-life in aqueous solution were also measured. Twenty compounds were mutagenic, with \"standard mutagenic concentrations\" (i.e. those producing 100 mutants/dish) of 0.0024--6500 micron. Standard mutagenic concentration was negatively correlated with the partition coefficient. Three compounds (ethyl 2-acetoxyethylnitrosocarbamate, nitrosocarbaryl, and methylnitrosobenzamide) were more active than the classic mutagen methylnitrosonitroguanidine. Nitrosocarbamates were at least 50 times more mutagenic than the corresponding nitrosoureas. Nitrosodihydrouracil and propylene-nitrosourea were more active than related compounds. Ethylnitrosocyanamide was 730 times more mutagenic than ethylnitrosourea. Fifteen of the test compounds (of which 14 were mutagenic) had previously been assayed in rats for carcinogenicity, all with positive results.", "contents": "Mutagenicity of 22 N-nitrosamides and related compounds for Salmonella typhimurium TA1535. Twenty-two N-nitrosamides and related compounds, including 14 nitrosoureas, 5 nitrosocarbamates, and one nitrosocyanamide, were tested at various concentrations for mutagenic activity towards Salmonella typhimurium TA1535 without the use of microsomes. The ether-water partition coefficient, solubility in water, and half-life in aqueous solution were also measured. Twenty compounds were mutagenic, with \"standard mutagenic concentrations\" (i.e. those producing 100 mutants/dish) of 0.0024--6500 micron. Standard mutagenic concentration was negatively correlated with the partition coefficient. Three compounds (ethyl 2-acetoxyethylnitrosocarbamate, nitrosocarbaryl, and methylnitrosobenzamide) were more active than the classic mutagen methylnitrosonitroguanidine. Nitrosocarbamates were at least 50 times more mutagenic than the corresponding nitrosoureas. Nitrosodihydrouracil and propylene-nitrosourea were more active than related compounds. Ethylnitrosocyanamide was 730 times more mutagenic than ethylnitrosourea. Fifteen of the test compounds (of which 14 were mutagenic) had previously been assayed in rats for carcinogenicity, all with positive results."}
{"id": "PMID:17833", "title": "Nitrosation in vitro and in vivo by sodium nitrite, and mutagenicity of nitrogenous pesticides.", "content": "37 nitrogenous pesticides, belonging to the chemical groups of amides, carbamates and ureas, were nitrosated with sodium nitrite in vitro. The nitrosated compounds were tested for mutagenic activity in the bacterial spot test with Salmonella typhimurium his G 46. Those pesticides reacting positively in this test after nitrosation were then fed to mice in combination with sodium nitrite in order to assess the formation and mutagenicity of these nitroso compounds in vivo. With the already known exception of ethylenethiourea (ETU), no pesticide produced enhanced numbers of micronuclei in mouse bone-marrow erythrocytes when fed together with nitrite. Dose-response experiments with intraperitoneal injection of N-nitroso-ETU revealed an apparent no-effect level of about 15--18 mg/kg. The findings are correlated with the pesticide residues actually present in the environment.", "contents": "Nitrosation in vitro and in vivo by sodium nitrite, and mutagenicity of nitrogenous pesticides. 37 nitrogenous pesticides, belonging to the chemical groups of amides, carbamates and ureas, were nitrosated with sodium nitrite in vitro. The nitrosated compounds were tested for mutagenic activity in the bacterial spot test with Salmonella typhimurium his G 46. Those pesticides reacting positively in this test after nitrosation were then fed to mice in combination with sodium nitrite in order to assess the formation and mutagenicity of these nitroso compounds in vivo. With the already known exception of ethylenethiourea (ETU), no pesticide produced enhanced numbers of micronuclei in mouse bone-marrow erythrocytes when fed together with nitrite. Dose-response experiments with intraperitoneal injection of N-nitroso-ETU revealed an apparent no-effect level of about 15--18 mg/kg. The findings are correlated with the pesticide residues actually present in the environment."}
{"id": "PMID:17845", "title": "Detection of gastroesophageal reflux in the pediatric-age patient by esophageal intraluminal pH probe measurement (Tuttle test).", "content": "The esophageal intraluminal pH probe test (Tuttle test) was used in 24 pediatric-age patients who had symptoms of gastroesophageal (GE) reflux to determine its sensitivity in detecting gastric acid reflux and to document its usefulness as a prognostic indicator. Eight children had a positive Tuttle test. Six of these patients failed a trial of medical management and required surgery to control their symptoms. None of these patients had GE reflux on esophagrams. Only one of 16 children with a negative test required surgery. This patient also did not have GE reflux on esophagram. The Tuttle test should be included in the diagnostic evaluation of pediatric patients with the clinical presentation of GE reflux.", "contents": "Detection of gastroesophageal reflux in the pediatric-age patient by esophageal intraluminal pH probe measurement (Tuttle test). The esophageal intraluminal pH probe test (Tuttle test) was used in 24 pediatric-age patients who had symptoms of gastroesophageal (GE) reflux to determine its sensitivity in detecting gastric acid reflux and to document its usefulness as a prognostic indicator. Eight children had a positive Tuttle test. Six of these patients failed a trial of medical management and required surgery to control their symptoms. None of these patients had GE reflux on esophagrams. Only one of 16 children with a negative test required surgery. This patient also did not have GE reflux on esophagram. The Tuttle test should be included in the diagnostic evaluation of pediatric patients with the clinical presentation of GE reflux."}
{"id": "PMID:17844", "title": "alpha-L-fucosidase in cultured skin fibroblasts from normal subjects and fucosidosis patients.", "content": "alpha-L-Fucosidase (EC 3.2.1.51) activity was studied in cultured skin fibroblasts obtained from 23 members of a family in which two cases of fucosidosis type 2 had occurred and in the fibroblasts of a patient with fucosidosis type 1. Both the 4-methylumbelliferyl glycoside and the p-nitrophenyl derivative were used as substrates. pH activity profiles showed two major peaks of activity. With the fluorogenic substrate pH optimum was at 4.5, whereas with the colorigenic substrate maximum activity was at pH 5.7. No activity was found in the fibroblasts of the three patients with the colorimetric assay. With the fluorometric assay the mean activity in the two patients with fucosidosis type 2 was 4.1 and 2.8 (range 1.3-9.9); activity in the patient with fucosidosis type 1 was 4.6 nmol 4-methylumbelliferone/mg protein/hr (range 1.0-8.6). The specific activity in the lysates of the patients' fibroblasts decreased as the amount of cellular protein used per assay increased. Fucosidosis fibroblasts cultured for 3 and 5 days in medium without fetal calf serum showed almost the same levels of apparent residual activity as fibroblasts cultured in medium containing fetal calf serum. Maximum activity in the deficient fibroblasts was at pH 4.5-4.75. Mixing experiments between lysates of both of fucosidosis and a normal fibroblast strain showed the expected enzymatic activities. The mean alpha-fucosidase activity in four heterozygotes for fucosidosis was 37.6 (range 24.1-48.7) and 30.3 (range 19.0-44.1) nmol final product split/mg protein/hr with the fluorogenic and the colorigenic substrate, respectively. In 12 normal fibroblast strains the mean activity +/- SD was 85.3 +/- 24.4 (range 50.8-129.3) and 67.6 +/- 21.1 (range 31.1-118.3). However, in four family members in which the alpha-L-fucosidase phenotype (by isoelectric focusing) was type 2-1, and who should therefore be carrying two normal alleles, the activity was within the heterozygote range. This indicates that occasional overlap between normal subjects and carriers may be present in cultured skin fibroblasts. Increased specific activity of alpha-L-fucosidase at pH 3.2-4.0 was observed after incubation of cell lysates with neuraminidase. The alpha-L-fucosidase activity did not show any increase after fusion between fucosidosis fibroblasts type 1 and 2.", "contents": "alpha-L-fucosidase in cultured skin fibroblasts from normal subjects and fucosidosis patients. alpha-L-Fucosidase (EC 3.2.1.51) activity was studied in cultured skin fibroblasts obtained from 23 members of a family in which two cases of fucosidosis type 2 had occurred and in the fibroblasts of a patient with fucosidosis type 1. Both the 4-methylumbelliferyl glycoside and the p-nitrophenyl derivative were used as substrates. pH activity profiles showed two major peaks of activity. With the fluorogenic substrate pH optimum was at 4.5, whereas with the colorigenic substrate maximum activity was at pH 5.7. No activity was found in the fibroblasts of the three patients with the colorimetric assay. With the fluorometric assay the mean activity in the two patients with fucosidosis type 2 was 4.1 and 2.8 (range 1.3-9.9); activity in the patient with fucosidosis type 1 was 4.6 nmol 4-methylumbelliferone/mg protein/hr (range 1.0-8.6). The specific activity in the lysates of the patients' fibroblasts decreased as the amount of cellular protein used per assay increased. Fucosidosis fibroblasts cultured for 3 and 5 days in medium without fetal calf serum showed almost the same levels of apparent residual activity as fibroblasts cultured in medium containing fetal calf serum. Maximum activity in the deficient fibroblasts was at pH 4.5-4.75. Mixing experiments between lysates of both of fucosidosis and a normal fibroblast strain showed the expected enzymatic activities. The mean alpha-fucosidase activity in four heterozygotes for fucosidosis was 37.6 (range 24.1-48.7) and 30.3 (range 19.0-44.1) nmol final product split/mg protein/hr with the fluorogenic and the colorigenic substrate, respectively. In 12 normal fibroblast strains the mean activity +/- SD was 85.3 +/- 24.4 (range 50.8-129.3) and 67.6 +/- 21.1 (range 31.1-118.3). However, in four family members in which the alpha-L-fucosidase phenotype (by isoelectric focusing) was type 2-1, and who should therefore be carrying two normal alleles, the activity was within the heterozygote range. This indicates that occasional overlap between normal subjects and carriers may be present in cultured skin fibroblasts. Increased specific activity of alpha-L-fucosidase at pH 3.2-4.0 was observed after incubation of cell lysates with neuraminidase. The alpha-L-fucosidase activity did not show any increase after fusion between fucosidosis fibroblasts type 1 and 2."}
{"id": "PMID:17848", "title": "[The detection of soluble bacterial antigens studied in various pathological substances using counterimmunoelectrophoresis. Contribution to diagnosis(151 cases)].", "content": "Examinations for soluble bacterial antigens using counter-immunoelectrophoresis (C.I.E.) was carried out in 151 patients suspected of suffering from various infectious syndrome were successful for S. pneumoniae, H. influenzae b, N. meningitis, sero-group B and D streptococcus. Thus meningitis and pneumonia represent those areas in which the technique is particularly useful. Apart from its rapidity--result in a hour--C.I.E., in association with bacteriology, makes possible an increase in aetiological diagnosis of 27% with H. influenzae b, 24% with S. pneumoniae and 6% with N. meningitidis (lower result by virtue of technical difficulties with sero-group B). Thus using this technique we were able to reach an aetiological diagnosis in 10 (23.8%) out of 42 cases of purulent meningitis where blind antibiotic therapy had already been given. These two advantages--rapidity and increase in aetiological diagnosis--justify the introduction of this simple technique in every medical microbiology laboratory.", "contents": "[The detection of soluble bacterial antigens studied in various pathological substances using counterimmunoelectrophoresis. Contribution to diagnosis(151 cases)]. Examinations for soluble bacterial antigens using counter-immunoelectrophoresis (C.I.E.) was carried out in 151 patients suspected of suffering from various infectious syndrome were successful for S. pneumoniae, H. influenzae b, N. meningitis, sero-group B and D streptococcus. Thus meningitis and pneumonia represent those areas in which the technique is particularly useful. Apart from its rapidity--result in a hour--C.I.E., in association with bacteriology, makes possible an increase in aetiological diagnosis of 27% with H. influenzae b, 24% with S. pneumoniae and 6% with N. meningitidis (lower result by virtue of technical difficulties with sero-group B). Thus using this technique we were able to reach an aetiological diagnosis in 10 (23.8%) out of 42 cases of purulent meningitis where blind antibiotic therapy had already been given. These two advantages--rapidity and increase in aetiological diagnosis--justify the introduction of this simple technique in every medical microbiology laboratory."}
{"id": "PMID:17853", "title": "An investigation of renal function in chronic bronchitis.", "content": "An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis.", "contents": "An investigation of renal function in chronic bronchitis. An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis."}
{"id": "PMID:17854", "title": "Polyarteritis nodosa of the liver: a report of two cases.", "content": "Two patients with liver disease due to polyarteritis nodosa are described. They presented in a similar manner, with a swinging fever, a polymorphonuclear leucocytosis and high alkaline phosphatase levels, but the natural history of the illness was different, with revocery in one and death in the other.", "contents": "Polyarteritis nodosa of the liver: a report of two cases. Two patients with liver disease due to polyarteritis nodosa are described. They presented in a similar manner, with a swinging fever, a polymorphonuclear leucocytosis and high alkaline phosphatase levels, but the natural history of the illness was different, with revocery in one and death in the other."}
{"id": "PMID:17858", "title": "[Assessment of the mental load of flight managers and of perforating machine operators by means of measuring the residual mental capacity via the subsidiary task method].", "content": "The purpose of the study is to evaluate mental loading due to working activities in two occupational groups--flight managers and punching machine operators. Changes in residual mental capacity are studied in relation to character of the specific work performed and working conditions. Residual capacity changes, measured with the method of double task assignment, disclose an essential difference in the nature of labour inherent of the two professions under study. The increased quantity of tasks performed under normal conditions of work exerts less influence on the level of residual mental capacity than work assignments fulfilled under complicated situations (such as bad weather conditions and the like). The level of residual mental capacity is likewise altered under the effect of fatigue in the course of the working day.", "contents": "[Assessment of the mental load of flight managers and of perforating machine operators by means of measuring the residual mental capacity via the subsidiary task method]. The purpose of the study is to evaluate mental loading due to working activities in two occupational groups--flight managers and punching machine operators. Changes in residual mental capacity are studied in relation to character of the specific work performed and working conditions. Residual capacity changes, measured with the method of double task assignment, disclose an essential difference in the nature of labour inherent of the two professions under study. The increased quantity of tasks performed under normal conditions of work exerts less influence on the level of residual mental capacity than work assignments fulfilled under complicated situations (such as bad weather conditions and the like). The level of residual mental capacity is likewise altered under the effect of fatigue in the course of the working day."}
{"id": "PMID:17872", "title": "Non-equilibrium freezing behaviour of aqueous systems.", "content": "The tendencies to non-equilibrium freezing behaviour commonly noted in representative aqueous systems derive from bulk and surface properties according to the circumstances. Supercooling and supersaturation are limited by heterogeneous nucleation in the presence of solid impurities. Homogeneous nucleation has been observed in aqueous systems freed from interfering solids. Once initiated, crystal growth is ofter slowed and, very frequently, terminated with increasing viscosity. Nor does ice first formed always succeed in assuming its most stable crystalline form. Many of the more significant measurements on a given systeatter permitting the simultaneous representation of thermodynamic and non-equilibrium properties. The diagram incorporated equilibrium melting points, heterogeneous nucleation temperatures, homogeneous nucleation temperatures, glass transition and devitrification temperatures, recrystallization temperatures, and, where appropriate, solute solubilities and eutectic temperatures. Taken together, the findings on modle systems aid the identification of the kinetic and thermodynamic factors responsible for the freezing-thawing survival of living cells.", "contents": "Non-equilibrium freezing behaviour of aqueous systems. The tendencies to non-equilibrium freezing behaviour commonly noted in representative aqueous systems derive from bulk and surface properties according to the circumstances. Supercooling and supersaturation are limited by heterogeneous nucleation in the presence of solid impurities. Homogeneous nucleation has been observed in aqueous systems freed from interfering solids. Once initiated, crystal growth is ofter slowed and, very frequently, terminated with increasing viscosity. Nor does ice first formed always succeed in assuming its most stable crystalline form. Many of the more significant measurements on a given systeatter permitting the simultaneous representation of thermodynamic and non-equilibrium properties. The diagram incorporated equilibrium melting points, heterogeneous nucleation temperatures, homogeneous nucleation temperatures, glass transition and devitrification temperatures, recrystallization temperatures, and, where appropriate, solute solubilities and eutectic temperatures. Taken together, the findings on modle systems aid the identification of the kinetic and thermodynamic factors responsible for the freezing-thawing survival of living cells."}
{"id": "PMID:17873", "title": "Water transport and cell survival in cryobiological procedures.", "content": "Living cells may be cooled to 77 K (liquid nitrogen) either to destroy them selectively or to store them for long periods. Water transport across the cell membranes during freezing and thawing is a primary factor determining whether the cells survive. These water movements are controlled by phase changes both intracellular and extracellular and by other factors such as the nature of any cryoprotective agent present, and the rates of cooling and thawing. The relation between cooling procedure, water transport and cell survival is discussed. In particular, the crucial r\u00f4le of dilution shock is emphasized: this is the damage to cells induced during the dilution that occurs both as ice melts during rewarming and when any cryoprotective additives are removed after thawing. Apart from the usefulness of understanding these processes for maximizing preservation or controlling selective destruction, the diverse responses of cells to different combinations of water transport and temperature changes appear likely to provide basic information on the properties of cell membranes.", "contents": "Water transport and cell survival in cryobiological procedures. Living cells may be cooled to 77 K (liquid nitrogen) either to destroy them selectively or to store them for long periods. Water transport across the cell membranes during freezing and thawing is a primary factor determining whether the cells survive. These water movements are controlled by phase changes both intracellular and extracellular and by other factors such as the nature of any cryoprotective agent present, and the rates of cooling and thawing. The relation between cooling procedure, water transport and cell survival is discussed. In particular, the crucial r\u00f4le of dilution shock is emphasized: this is the damage to cells induced during the dilution that occurs both as ice melts during rewarming and when any cryoprotective additives are removed after thawing. Apart from the usefulness of understanding these processes for maximizing preservation or controlling selective destruction, the diverse responses of cells to different combinations of water transport and temperature changes appear likely to provide basic information on the properties of cell membranes."}
{"id": "PMID:17874", "title": "The organization and function of water in protein crystals.", "content": "Dry proteins are dead, or at best asleep. Substitution of D2O can drastically alter biological activity. Water is thus essential in maintaining the structural integrity of biologically active macromolecules, and is implicated in their functioning. Such water may occupy a range of dynamical states, from being strongly bound and localized, to more labile and 'liquid-like'. Spatially ordering the macromolecules aids the search for the more localized water molecules. For example, diffraction experiments on singly crystals can resolve 'bound' water molecules within a protein molecule--ofter at active sites, coordinated to metals or ions. Less precise information is obtained on the partially occupied external water sites, which are of importance to the folding and dynamics of the biomolecule. Orientation of fibrous molecules increases the information obtainable from n.m.r. experiments. Combination of other experimental results on disordered aggregates (e.g. in solution) with chemical and structural data on the macromolecule and water itself yields useful, if circumstantial, information. Statistical and computer techniques may help to elucidate the complex nature of water-protein interactions, and to interpret the results of more complex experiments.", "contents": "The organization and function of water in protein crystals. Dry proteins are dead, or at best asleep. Substitution of D2O can drastically alter biological activity. Water is thus essential in maintaining the structural integrity of biologically active macromolecules, and is implicated in their functioning. Such water may occupy a range of dynamical states, from being strongly bound and localized, to more labile and 'liquid-like'. Spatially ordering the macromolecules aids the search for the more localized water molecules. For example, diffraction experiments on singly crystals can resolve 'bound' water molecules within a protein molecule--ofter at active sites, coordinated to metals or ions. Less precise information is obtained on the partially occupied external water sites, which are of importance to the folding and dynamics of the biomolecule. Orientation of fibrous molecules increases the information obtainable from n.m.r. experiments. Combination of other experimental results on disordered aggregates (e.g. in solution) with chemical and structural data on the macromolecule and water itself yields useful, if circumstantial, information. Statistical and computer techniques may help to elucidate the complex nature of water-protein interactions, and to interpret the results of more complex experiments."}
{"id": "PMID:17878", "title": "Theoretical approaches to the intermolecular nature of water.", "content": "A brief review is presented of recent advances in theoretical understanding of liquid water. These advances include detailed quantitative specification of water-molecule interaction potentials, and development of several techniques in statistical mechanics for predicting molecular order in the liquid. Specifically, computer simulation now plays a particularly important r\u00f4le. A labile, defective, random network picture for the liquid is the only consistently supported possibility. Implications of this picture for  an explanation of hydrophobic solvation and bonding are mentioned. Furthermore, the apparent cooperative restructuring of the random network near the supercolling limit suggests that a dielectric anomaly might exist in this r\u00e9gime. Several areas for future development of water theory are suggested, bearing specifically on phenomena of biological interest.", "contents": "Theoretical approaches to the intermolecular nature of water. A brief review is presented of recent advances in theoretical understanding of liquid water. These advances include detailed quantitative specification of water-molecule interaction potentials, and development of several techniques in statistical mechanics for predicting molecular order in the liquid. Specifically, computer simulation now plays a particularly important r\u00f4le. A labile, defective, random network picture for the liquid is the only consistently supported possibility. Implications of this picture for  an explanation of hydrophobic solvation and bonding are mentioned. Furthermore, the apparent cooperative restructuring of the random network near the supercolling limit suggests that a dielectric anomaly might exist in this r\u00e9gime. Several areas for future development of water theory are suggested, bearing specifically on phenomena of biological interest."}
{"id": "PMID:17881", "title": "Stress-induced alterations of cyclic nucleotide levels in brain: effects of centrally acting drugs.", "content": "Acute stressing procedures cause a shortlasting increase in the levels of guanosie 3',5'-monophosphate (cGMP) in mouse brain without significantly influencing the concentrations of adenosine 3'-5'-monophosphate (cAMP). Animals were pretreated with various centrally acting drugs before being stressed in order to study the involvement of specific neurotransmitters in the stress-induced rise of cGMP levels. Centrally depressant drugs affecting different synaptic mechanisms, such as chlorpromazine, reserpine, haloperidol, diazepam, and pentobarbital, inhibited the cCMP increase elicited by stress. Pretreatment with atropine, diphenhydramine, antazoline, cyproheptadine, phentolamine, bunitrolol, and indomethacin had no significant effect. Clonidine and both the (-)- and (+)-isomers of propranolol inhibited the stress-induced cGMP increase in a dose-related manner. Our results suggest that norepinephrine, serotonin, acetylcholine, or prostaglandins are not involved in the elevation of cGMP levels elicited by acute stress. Participation of other neurotransmitter(s), such as dopamine or GABA, cannot be excluded.", "contents": "Stress-induced alterations of cyclic nucleotide levels in brain: effects of centrally acting drugs. Acute stressing procedures cause a shortlasting increase in the levels of guanosie 3',5'-monophosphate (cGMP) in mouse brain without significantly influencing the concentrations of adenosine 3'-5'-monophosphate (cAMP). Animals were pretreated with various centrally acting drugs before being stressed in order to study the involvement of specific neurotransmitters in the stress-induced rise of cGMP levels. Centrally depressant drugs affecting different synaptic mechanisms, such as chlorpromazine, reserpine, haloperidol, diazepam, and pentobarbital, inhibited the cCMP increase elicited by stress. Pretreatment with atropine, diphenhydramine, antazoline, cyproheptadine, phentolamine, bunitrolol, and indomethacin had no significant effect. Clonidine and both the (-)- and (+)-isomers of propranolol inhibited the stress-induced cGMP increase in a dose-related manner. Our results suggest that norepinephrine, serotonin, acetylcholine, or prostaglandins are not involved in the elevation of cGMP levels elicited by acute stress. Participation of other neurotransmitter(s), such as dopamine or GABA, cannot be excluded."}
{"id": "PMID:17891", "title": "Physiological role of yeasts NAD(P)+ and NADP+-linked aldehyde dehydrogenases.", "content": "The activity of NAD+ and NADP+-linked aldehyde dehydrogenases has been investigated in yeast cells grown under different conditions. As occurs in other dehydrogenase reactions the NAD(P)+-linked enzyme was strongly repressed in all hypoxic conditions; nervetheless, the NADP+-linked enzyme was active. The results suggest that the NAD(P)+ aldehyde dehydrogenase is involved in the oxidation of ethanol to acetyl-CoA, and that when the pyruvate dehydrogenase complex is repressed the NADP+-linked aldehyde dehydrogenase is operative as an alternative pathway from pyruvate to acetyl-CoA: pyruvate leads to acetaldehyde leads to acetate leads to acetyl-Coa. In these conditions the supply of NADPH is advantageous to the cellular economy for biosynthetic purposes. Short term adaptation experiments suggest that the regulation of the levels of the aldehyde dehydrogenase-NAD(P)+ takes place by the de novo synthesis of the enzyme.", "contents": "Physiological role of yeasts NAD(P)+ and NADP+-linked aldehyde dehydrogenases. The activity of NAD+ and NADP+-linked aldehyde dehydrogenases has been investigated in yeast cells grown under different conditions. As occurs in other dehydrogenase reactions the NAD(P)+-linked enzyme was strongly repressed in all hypoxic conditions; nervetheless, the NADP+-linked enzyme was active. The results suggest that the NAD(P)+ aldehyde dehydrogenase is involved in the oxidation of ethanol to acetyl-CoA, and that when the pyruvate dehydrogenase complex is repressed the NADP+-linked aldehyde dehydrogenase is operative as an alternative pathway from pyruvate to acetyl-CoA: pyruvate leads to acetaldehyde leads to acetate leads to acetyl-Coa. In these conditions the supply of NADPH is advantageous to the cellular economy for biosynthetic purposes. Short term adaptation experiments suggest that the regulation of the levels of the aldehyde dehydrogenase-NAD(P)+ takes place by the de novo synthesis of the enzyme."}
{"id": "PMID:17892", "title": "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors.", "content": "Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects.", "contents": "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects."}
{"id": "PMID:17894", "title": "Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine.", "content": "Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues.", "contents": "Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine. Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues."}
{"id": "PMID:17895", "title": "Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide.", "content": "Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms.", "contents": "Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide. Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms."}
{"id": "PMID:17896", "title": "Brain gamma-glutamyl transpeptidase levels in mice genetically selected for sensitivity to ethanol.", "content": "The present study describes the regional distribution of the enzyme gamma-glutamyl transpeptidase for two lines of mice (long-sleep and short-sleep) selectively bred for differences in sleep-time after the administration of ethanol. The long-sleep animals exhibited higher levels of the enzyme in all areas of brain.", "contents": "Brain gamma-glutamyl transpeptidase levels in mice genetically selected for sensitivity to ethanol. The present study describes the regional distribution of the enzyme gamma-glutamyl transpeptidase for two lines of mice (long-sleep and short-sleep) selectively bred for differences in sleep-time after the administration of ethanol. The long-sleep animals exhibited higher levels of the enzyme in all areas of brain."}
{"id": "PMID:17898", "title": "Blood-gas properties and function in the fossorial mole rat under normal and hypoxic-hypercapnic atmospheric conditions.", "content": "Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml. P50 (at pH 7.4 and 37 degrees C) was 29.5 +/- 0.5 mm Hg. Oxygen capacity averaged 20.2 +/- 0.4 vol% and the Hill coefficient was 2.9 +/- 0.1. The Bohr effect was -0.53 +/- 0.02 (deltalog P/deltapH). The temperature coefficient was 0.0152 +/- 0.0014 (deltalog P/delta degrees C). The Haldane effect was 4.8 +/- 0.5 (deltaCCO2 vol%)at PCO2 =40 mm Hg. Steady-state partial pressures in gas pockets were PO2 = 15.1 +/- 1.4 mm Hg and PCO2 = 85.8 +/- 3.9 mm Hg in normoxia, and 11.5 +/- 3.0 and 101.8 +/- 3.5 repectively in hypoxia-hypercapnia (PIO2 congruent to 85 mm Hg). Under the same conditions 2,3-DPG dropped from 0.87 and 0.88 to 0.62 and 0.65 (mol/mol Hb) in the rat and in the white rat, respectively. Heart muscle myoglobin concentration of the mole rat (1.44 mg/g) did not differ significantly from that of the white rat (1.96 mg/g), whereas masseter myoglobin was 4.0 mg/g--significantly different from the rat (1.21 mg/g). Results indicate that the strategy used by the mole rat to maintain a normal metabolic rate under variable atmospheric conditions, besides having high oxygen affinity, is to expand the physiological range of the oxygen dissociation curve to very low oxygen tensions, at the expense of its acid-base regulation. The regulation of the shape of the oxygen dissociation curve is discussed.", "contents": "Blood-gas properties and function in the fossorial mole rat under normal and hypoxic-hypercapnic atmospheric conditions. Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml. P50 (at pH 7.4 and 37 degrees C) was 29.5 +/- 0.5 mm Hg. Oxygen capacity averaged 20.2 +/- 0.4 vol% and the Hill coefficient was 2.9 +/- 0.1. The Bohr effect was -0.53 +/- 0.02 (deltalog P/deltapH). The temperature coefficient was 0.0152 +/- 0.0014 (deltalog P/delta degrees C). The Haldane effect was 4.8 +/- 0.5 (deltaCCO2 vol%)at PCO2 =40 mm Hg. Steady-state partial pressures in gas pockets were PO2 = 15.1 +/- 1.4 mm Hg and PCO2 = 85.8 +/- 3.9 mm Hg in normoxia, and 11.5 +/- 3.0 and 101.8 +/- 3.5 repectively in hypoxia-hypercapnia (PIO2 congruent to 85 mm Hg). Under the same conditions 2,3-DPG dropped from 0.87 and 0.88 to 0.62 and 0.65 (mol/mol Hb) in the rat and in the white rat, respectively. Heart muscle myoglobin concentration of the mole rat (1.44 mg/g) did not differ significantly from that of the white rat (1.96 mg/g), whereas masseter myoglobin was 4.0 mg/g--significantly different from the rat (1.21 mg/g). Results indicate that the strategy used by the mole rat to maintain a normal metabolic rate under variable atmospheric conditions, besides having high oxygen affinity, is to expand the physiological range of the oxygen dissociation curve to very low oxygen tensions, at the expense of its acid-base regulation. The regulation of the shape of the oxygen dissociation curve is discussed."}
{"id": "PMID:17899", "title": "Crayfish respiration as a function of water oxygenation.", "content": "Crayfish, Astacus leptodactylus, for several hours breathed water equilibrated either with a hypoxic gas mixture, or air, or oxygen. The hydrostatic pressure in the right epibranchial cavity was recorded and the left epibranchial water sempled from time to time. The higher the water oxygenation, the less the duration of ventilation, the frequency of the scaphognathite beats which ensure water convection, the negative of the water hydrostatic pressure relative to ambient water pressure, and the respired water flow. The water convection per unit quantity of oxygen consumed decreased by a factor of about 20 when the animal passed from hypoxic water at PO2 of 72 torr to hyperoxic water at PO2 of 697 torr. Prolonged hyperoxia, up to 100 days, results in a hypercapnic acidosis of the prebranchial blood. pH decreased about 0.2 unit, PCO2 increased from 2.5 torr to a value of 6 torr, and [HCO-3] from 6 to a value of 9 meq-L-1. This hypercapnic acidosis remained uncompensated during several weeks exposure to hyperoxia. Observations on the fresh water crayfish, a marine crab, and several species of fish, suggest that in aquatic animals (1) the ventilatory activity depends greatly on the degree of water oxygenation: the higher the water oxygenation, the lower the ventilation; (2) the change of ventilation may be accompanied by a new equilibrium of the blood acid-base status, quite different from that observed in normoxia.", "contents": "Crayfish respiration as a function of water oxygenation. Crayfish, Astacus leptodactylus, for several hours breathed water equilibrated either with a hypoxic gas mixture, or air, or oxygen. The hydrostatic pressure in the right epibranchial cavity was recorded and the left epibranchial water sempled from time to time. The higher the water oxygenation, the less the duration of ventilation, the frequency of the scaphognathite beats which ensure water convection, the negative of the water hydrostatic pressure relative to ambient water pressure, and the respired water flow. The water convection per unit quantity of oxygen consumed decreased by a factor of about 20 when the animal passed from hypoxic water at PO2 of 72 torr to hyperoxic water at PO2 of 697 torr. Prolonged hyperoxia, up to 100 days, results in a hypercapnic acidosis of the prebranchial blood. pH decreased about 0.2 unit, PCO2 increased from 2.5 torr to a value of 6 torr, and [HCO-3] from 6 to a value of 9 meq-L-1. This hypercapnic acidosis remained uncompensated during several weeks exposure to hyperoxia. Observations on the fresh water crayfish, a marine crab, and several species of fish, suggest that in aquatic animals (1) the ventilatory activity depends greatly on the degree of water oxygenation: the higher the water oxygenation, the lower the ventilation; (2) the change of ventilation may be accompanied by a new equilibrium of the blood acid-base status, quite different from that observed in normoxia."}
{"id": "PMID:17916", "title": "Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor.", "content": "The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF.", "contents": "Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor. The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF."}
{"id": "PMID:17917", "title": "Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover.", "content": "The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover.", "contents": "Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover. The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover."}
{"id": "PMID:17918", "title": "Electrically coupled, photosensitive neurons control swimming in a jellyfish.", "content": "Central neurons in Polyorchis (Hydromedusae) were impaled with microelectrodes, and conventional resting potentials were obtained. The waveform of action potentials recorded concurrently with swimming events shows evidence of electrotonic coupling between these neurons, which are also directly photosensitive and receive excitatory synaptic input from other conduction systems.", "contents": "Electrically coupled, photosensitive neurons control swimming in a jellyfish. Central neurons in Polyorchis (Hydromedusae) were impaled with microelectrodes, and conventional resting potentials were obtained. The waveform of action potentials recorded concurrently with swimming events shows evidence of electrotonic coupling between these neurons, which are also directly photosensitive and receive excitatory synaptic input from other conduction systems."}
{"id": "PMID:17914", "title": "[Polyneuropathy due to \"allergic vasculitis\" possibly related to australia antigen. (author's transl)].", "content": "The authors describe a case of flaccid tetraplegia due to a polyneuropathy in a man aged 50 years, progressing rapidly to death from mesenteric infarction. As significant abnormalities, the hematologic examinations revealed a very high erythrocyte sedimentation rate, a marked leukocytosis and a positive Australia antigen in repeated controls. In spite of the clinical picture being that of a symmetrical polyneuropathy rather than that of mononeuritis multiplex, the diagnose of a collagenosis was suspected. Nevertheless steroid treatment was not given because the patient had a peptic ulcer. On histological investigation many focal infarctions were found in several internal organs but the brain was pratically normal. Instead the nerve trunks examined (the sciatic nerve and the lumbo-sacral plexus) showed gross changes in the vasa nervorum represented by abundant perivascular cuffing and marked evidence of axonal degeneration secondary to an ischaemic damage. In the kidneys there were definite signs of membranous glomerulitis. The pathological findings in this fatal case of diffuse peripheral involvement were not those of classical periarteritis nodosa, but showed the picture of so-called \"allergic vasculitis\". This type of blood vessels inflammation is now assumed to be part of an immune-complex disease, in which the Australia antigen could be one of the causative agents.", "contents": "[Polyneuropathy due to \"allergic vasculitis\" possibly related to australia antigen. (author's transl)]. The authors describe a case of flaccid tetraplegia due to a polyneuropathy in a man aged 50 years, progressing rapidly to death from mesenteric infarction. As significant abnormalities, the hematologic examinations revealed a very high erythrocyte sedimentation rate, a marked leukocytosis and a positive Australia antigen in repeated controls. In spite of the clinical picture being that of a symmetrical polyneuropathy rather than that of mononeuritis multiplex, the diagnose of a collagenosis was suspected. Nevertheless steroid treatment was not given because the patient had a peptic ulcer. On histological investigation many focal infarctions were found in several internal organs but the brain was pratically normal. Instead the nerve trunks examined (the sciatic nerve and the lumbo-sacral plexus) showed gross changes in the vasa nervorum represented by abundant perivascular cuffing and marked evidence of axonal degeneration secondary to an ischaemic damage. In the kidneys there were definite signs of membranous glomerulitis. The pathological findings in this fatal case of diffuse peripheral involvement were not those of classical periarteritis nodosa, but showed the picture of so-called \"allergic vasculitis\". This type of blood vessels inflammation is now assumed to be part of an immune-complex disease, in which the Australia antigen could be one of the causative agents."}
{"id": "PMID:17919", "title": "Stimulation of in vitro translation of messenger RNA by actinomycin D and cordycepin.", "content": "Actinomycin D and cordycepin were tested for their effect on translation in the wheat germ embryo extract and reticulocyte lysate assays for in vitro protein synthesis. Both drugs were found to stimulate the incorporation of 35S-labeled methionine into protein up to threefold as compared to control assays. This was true for synthesis directed by murine myeloma polyadenylate-containing RNA, tobacco mosaic virus RNA, and endogenous reticulocyte messenger RNA.", "contents": "Stimulation of in vitro translation of messenger RNA by actinomycin D and cordycepin. Actinomycin D and cordycepin were tested for their effect on translation in the wheat germ embryo extract and reticulocyte lysate assays for in vitro protein synthesis. Both drugs were found to stimulate the incorporation of 35S-labeled methionine into protein up to threefold as compared to control assays. This was true for synthesis directed by murine myeloma polyadenylate-containing RNA, tobacco mosaic virus RNA, and endogenous reticulocyte messenger RNA."}
{"id": "PMID:17920", "title": "Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate.", "content": "A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate.", "contents": "Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate. A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate."}
{"id": "PMID:17921", "title": "Calcium-dependent depression of a late outward current in snail neurons.", "content": "Neuron cell bodies of Helix pomatia were voltage-clamped with a 300-millisecond depolarizing test pulse (pulse II) delivered I second after a depolarizing conditioning pulse (pulse I). The outward current, measured 200 milliseconds after the onset of pulse. II, exhibited a strong depression that was dependent on the presence of pulse. I. The maximum depression of the pulse II outward current occurred when pulse I voltages lay in the range over which calcium influx is inferred to be greatest; depression of the pulse II current subsided as pulse I potentials approached the putative calcium equilibrium potential. In the presence of extracellular [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) or D600, the intensity of the pulse II current became largely independent of pulse I, approaching the values of maximal depression seen in normal Ringer solution. On the other hand, lowering the intracellular pH with extracellular carbon dioxide-carbonate buffer had no measurable effect on the outward currents. Other experiments showed that it is primarily the calcium-dependent, outward-current hump of the N-shaped late current-voltage curve that is depressed by presentation of the conditioning pulse. It was concluded that distinct from an early potassium-activating role, calcium entering during a depolarization leads, during a subsequent depolarization, to a depression of the calcium-activated potassium system that persists for many seconds.", "contents": "Calcium-dependent depression of a late outward current in snail neurons. Neuron cell bodies of Helix pomatia were voltage-clamped with a 300-millisecond depolarizing test pulse (pulse II) delivered I second after a depolarizing conditioning pulse (pulse I). The outward current, measured 200 milliseconds after the onset of pulse. II, exhibited a strong depression that was dependent on the presence of pulse. I. The maximum depression of the pulse II outward current occurred when pulse I voltages lay in the range over which calcium influx is inferred to be greatest; depression of the pulse II current subsided as pulse I potentials approached the putative calcium equilibrium potential. In the presence of extracellular [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) or D600, the intensity of the pulse II current became largely independent of pulse I, approaching the values of maximal depression seen in normal Ringer solution. On the other hand, lowering the intracellular pH with extracellular carbon dioxide-carbonate buffer had no measurable effect on the outward currents. Other experiments showed that it is primarily the calcium-dependent, outward-current hump of the N-shaped late current-voltage curve that is depressed by presentation of the conditioning pulse. It was concluded that distinct from an early potassium-activating role, calcium entering during a depolarization leads, during a subsequent depolarization, to a depression of the calcium-activated potassium system that persists for many seconds."}
{"id": "PMID:17922", "title": "Appetitive and replacement naps: EEG and behavior.", "content": "Consistent subjective, behavioral, and electroencephalographic sleep-stage differences were found between afternoon naps of 11 habitual appetitive nappers (who nap lightly for psychological reasons apparently unrelated to reported sleep needs) and 10 replacement nappers (who apparently nap regularly in response to temporary sleep deficits). Both types of naps were compared with naps of 12 confirmed non-nappers.", "contents": "Appetitive and replacement naps: EEG and behavior. Consistent subjective, behavioral, and electroencephalographic sleep-stage differences were found between afternoon naps of 11 habitual appetitive nappers (who nap lightly for psychological reasons apparently unrelated to reported sleep needs) and 10 replacement nappers (who apparently nap regularly in response to temporary sleep deficits). Both types of naps were compared with naps of 12 confirmed non-nappers."}
{"id": "PMID:17927", "title": "The use of counter-immuno-electrophoresis to identify causative organisms in bacterial meningitis: experience in Cape Town.", "content": "Crebrospinal fluid (CSF) from 142 patients was tested for the presence of Haemophilus influenzae, pneumococcal and meningococcal antigens by counter-immuno-electrophoresis with commercial antisera. Group- or type-specific antigen was detected in the CSF of 67% of 64 patients with meningitis proved by culture to be due to these organisms, and in 10 of 25 patients with purulent meningitis but negative cultures. No false positive results were obtained in 24 normal CSF specimens, or in the CSF of 29 patients with meningitis caused by other organisms. The diagnostic usefulness of this specific, relatively simple and rapid procedure is confirmed.", "contents": "The use of counter-immuno-electrophoresis to identify causative organisms in bacterial meningitis: experience in Cape Town. Crebrospinal fluid (CSF) from 142 patients was tested for the presence of Haemophilus influenzae, pneumococcal and meningococcal antigens by counter-immuno-electrophoresis with commercial antisera. Group- or type-specific antigen was detected in the CSF of 67% of 64 patients with meningitis proved by culture to be due to these organisms, and in 10 of 25 patients with purulent meningitis but negative cultures. No false positive results were obtained in 24 normal CSF specimens, or in the CSF of 29 patients with meningitis caused by other organisms. The diagnostic usefulness of this specific, relatively simple and rapid procedure is confirmed."}
{"id": "PMID:17928", "title": "Studies on myocardial reperfusion injury. I. Favorable modification by adjusting reperfusate pH.", "content": "This study tests the hypothesis that postischemic myocardial depression can be reduced by providing an initial reperfusate pH which is appropriate for myocardial temperature (i.e., metabolic systems function optimally when pH is kept slightly alkaline to the neutral point, which changes with temperature in concordance with the pK of water). Ten dogs underwent 1 hour of ischemic arrest with topical hypothermia (intramyocardial temperature 16+/-2 degrees C). The initial reperfusate (500 cc of blood from the extracorporeal circuit) was infused (100 cc/minute) into the proximal aorta just before removing the cross-clamp. Reperfusate pH was kept at 7.4 in five dogs (control) and raised to 7.8 with THAM [tris (hydroxymethyl) aminomethane] in five dogs. Measurements 30 minutes after reperfusion showed that raising reperfusate pH to 7.8 resulted in (1) higher subendocardial blood flows (109+/-20 vs 61 cc+/-8 cc/100 gm/minute), (2) redistribution of postischemic blood flow toward the subendocardium (endocardial/epicardial flow 1.25+/-0.1 vs 1.0+/-0.03), (3) higher left ventricular oxygen uptakes (0.046 vs 0.033 cc/100 gm/beat), (4) better postischemic left ventricular compliance (56+/-3% more compliant), and (5) improved left ventricular performance (88+/-7% recovery vs only 57+/-3% recovery at pH 7.4). Postischemic edema (2% water gain) was unchanged by pH modification. We conclude that initial reperfusion with the appropriate pH provides an optimal milieu for restoration of cellular metabolism, counteracts the acidosis of ischemia, and improves postischemic left ventricular blood flow, distribution, oxygen uptake, compliance, and performance.", "contents": "Studies on myocardial reperfusion injury. I. Favorable modification by adjusting reperfusate pH. This study tests the hypothesis that postischemic myocardial depression can be reduced by providing an initial reperfusate pH which is appropriate for myocardial temperature (i.e., metabolic systems function optimally when pH is kept slightly alkaline to the neutral point, which changes with temperature in concordance with the pK of water). Ten dogs underwent 1 hour of ischemic arrest with topical hypothermia (intramyocardial temperature 16+/-2 degrees C). The initial reperfusate (500 cc of blood from the extracorporeal circuit) was infused (100 cc/minute) into the proximal aorta just before removing the cross-clamp. Reperfusate pH was kept at 7.4 in five dogs (control) and raised to 7.8 with THAM [tris (hydroxymethyl) aminomethane] in five dogs. Measurements 30 minutes after reperfusion showed that raising reperfusate pH to 7.8 resulted in (1) higher subendocardial blood flows (109+/-20 vs 61 cc+/-8 cc/100 gm/minute), (2) redistribution of postischemic blood flow toward the subendocardium (endocardial/epicardial flow 1.25+/-0.1 vs 1.0+/-0.03), (3) higher left ventricular oxygen uptakes (0.046 vs 0.033 cc/100 gm/beat), (4) better postischemic left ventricular compliance (56+/-3% more compliant), and (5) improved left ventricular performance (88+/-7% recovery vs only 57+/-3% recovery at pH 7.4). Postischemic edema (2% water gain) was unchanged by pH modification. We conclude that initial reperfusion with the appropriate pH provides an optimal milieu for restoration of cellular metabolism, counteracts the acidosis of ischemia, and improves postischemic left ventricular blood flow, distribution, oxygen uptake, compliance, and performance."}
{"id": "PMID:17929", "title": "Endogenous serotonin in the control of gastric acid secretion.", "content": "In three dogs with Heidenhain pouches (HP), gastric fistulas (GF), and duodenal cannulas, acidification of the duodenum with 0.1N HC1 (5 ml/minute) resulted in significant inhibition of GF output (preacidification, 8.66+/-0.58 mEq/30 minutes; postacidification, 5.47+/-0.66 mEq/30 minutes) and elevated peripheral venous blood levels of serotonin (basal, 226+/-64 ng/ml; peak, 521+/-168 ng/ml). Infusion of exogenous serotonin to comparable blood levels (basal, 208+/-38 ng/ml; mean postacidification, 571+/-153 ng/ml) resulted in similar GF inhibition (preacidification, 9.17+/-0.92 mEq/30 minutes; postacidification, 6.49+/-0.56 mEq/30 minutes). Per increment in peripheral blood serotonin of 1 ng/ml, endogenous serotonin inhibited 54.59+/-12.99 muEq/hour and exogenous serotonin inhibited 46.54+/-10.39 muEq/hour, p greater than 0.05. Neither endogenously released nor exogenous serotonin inhibited HP acid output. Using mesenteric venous infusions of serotonin, significant amounts of immunoreactive serotonin were found to escape hepatic inactivation; basal peripheral venous levels of serotonin, 233+/-103 ng/ml, increased to 455+/-127 ng/ml at 10 minutes. During release of endogenous serotonin, 92+/-21% of portal venous serotonin was bound to platelets; in contrast, during intraportal serotonin infusion, only 59+/-18% of serotonin was platelet bound.", "contents": "Endogenous serotonin in the control of gastric acid secretion. In three dogs with Heidenhain pouches (HP), gastric fistulas (GF), and duodenal cannulas, acidification of the duodenum with 0.1N HC1 (5 ml/minute) resulted in significant inhibition of GF output (preacidification, 8.66+/-0.58 mEq/30 minutes; postacidification, 5.47+/-0.66 mEq/30 minutes) and elevated peripheral venous blood levels of serotonin (basal, 226+/-64 ng/ml; peak, 521+/-168 ng/ml). Infusion of exogenous serotonin to comparable blood levels (basal, 208+/-38 ng/ml; mean postacidification, 571+/-153 ng/ml) resulted in similar GF inhibition (preacidification, 9.17+/-0.92 mEq/30 minutes; postacidification, 6.49+/-0.56 mEq/30 minutes). Per increment in peripheral blood serotonin of 1 ng/ml, endogenous serotonin inhibited 54.59+/-12.99 muEq/hour and exogenous serotonin inhibited 46.54+/-10.39 muEq/hour, p greater than 0.05. Neither endogenously released nor exogenous serotonin inhibited HP acid output. Using mesenteric venous infusions of serotonin, significant amounts of immunoreactive serotonin were found to escape hepatic inactivation; basal peripheral venous levels of serotonin, 233+/-103 ng/ml, increased to 455+/-127 ng/ml at 10 minutes. During release of endogenous serotonin, 92+/-21% of portal venous serotonin was bound to platelets; in contrast, during intraportal serotonin infusion, only 59+/-18% of serotonin was platelet bound."}
{"id": "PMID:17932", "title": "Sensitization against non-HLA antigens following bone marrow graft rejection.", "content": "A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes.", "contents": "Sensitization against non-HLA antigens following bone marrow graft rejection. A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes."}
{"id": "PMID:17934", "title": "Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine.", "content": "Water solubility of the adenine catabolite 2,8 dihydroxyadenine (DOA) frequently forms the basis for predicting potential DOA crystal formation in human urine following infusion of adenine-fortified blood. Measurements relevant to solubility, ionic dissociation, and supersaturability of DOA in aqueous buffers and human urine at 37 C establish striking quantitative differences in the physico-chemical behavior of DOA in the two media. The basal solubility of DOA is 1.53 +/- 0.04 mg/1 (approximately 9 X 10(-6) M) in water (pH 6.5). DOA is an ampholyte characterized by aqueous thermodynamic macrodissociation constants of pKa1 = 2.6, pKa2 = 8.1, and pKa3 = 11.52. This compound displays pH-dependent solubility, although significant solubility increases beyond basal values do not occur within the physiologic pH range for human urine. Supersaturated aqueous solutions (three to sixteen times basal solubility) can be achieved but are unstable. In contrast, human urine at 37 C exhibits enhanced capacity for solubilizing DOA. In vitro basal solubility is 2.68 +/- 0.84 mg/1 at pH 5.0 and 4.97 +/- 1.49 mg/1 at pH 7.8. The apparent pK 2for DOA in urine of 7.9 to 8.1 is dependent upon urine osmolality. Urine can be supersaturated with Doa in vitro to approximately ten times its basal solubility by adding DOA solubilized in weak base, or by evaporation of a urine-DOA mixture. DOA remains supersaturated in urine for at least 16 hours despite gentle agitation. Little variation in in vitro DOA apparent supersaturation was found among urine samples from four normal individuals (40.38 +/- 3.33 mg/1). A patient receiving oral adenine exhibited urinary DOA solubility in considerable excess (96.0 mg/1) of that predicted from water and from in vitro urine solubility studies. Thus, water solubility of DOA is poorly predictive of in vitro and in vivo DOA solubility in human urine. On the basis of these data, estimates of the load of adenine-fortified blood expected to result in urinary DOA crystal formation may be revised upward.", "contents": "Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine. Water solubility of the adenine catabolite 2,8 dihydroxyadenine (DOA) frequently forms the basis for predicting potential DOA crystal formation in human urine following infusion of adenine-fortified blood. Measurements relevant to solubility, ionic dissociation, and supersaturability of DOA in aqueous buffers and human urine at 37 C establish striking quantitative differences in the physico-chemical behavior of DOA in the two media. The basal solubility of DOA is 1.53 +/- 0.04 mg/1 (approximately 9 X 10(-6) M) in water (pH 6.5). DOA is an ampholyte characterized by aqueous thermodynamic macrodissociation constants of pKa1 = 2.6, pKa2 = 8.1, and pKa3 = 11.52. This compound displays pH-dependent solubility, although significant solubility increases beyond basal values do not occur within the physiologic pH range for human urine. Supersaturated aqueous solutions (three to sixteen times basal solubility) can be achieved but are unstable. In contrast, human urine at 37 C exhibits enhanced capacity for solubilizing DOA. In vitro basal solubility is 2.68 +/- 0.84 mg/1 at pH 5.0 and 4.97 +/- 1.49 mg/1 at pH 7.8. The apparent pK 2for DOA in urine of 7.9 to 8.1 is dependent upon urine osmolality. Urine can be supersaturated with Doa in vitro to approximately ten times its basal solubility by adding DOA solubilized in weak base, or by evaporation of a urine-DOA mixture. DOA remains supersaturated in urine for at least 16 hours despite gentle agitation. Little variation in in vitro DOA apparent supersaturation was found among urine samples from four normal individuals (40.38 +/- 3.33 mg/1). A patient receiving oral adenine exhibited urinary DOA solubility in considerable excess (96.0 mg/1) of that predicted from water and from in vitro urine solubility studies. Thus, water solubility of DOA is poorly predictive of in vitro and in vivo DOA solubility in human urine. On the basis of these data, estimates of the load of adenine-fortified blood expected to result in urinary DOA crystal formation may be revised upward."}
{"id": "PMID:17940", "title": "Uropharmacology: v. choline esters and other parasympathomimetic drugs.", "content": "Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response.", "contents": "Uropharmacology: v. choline esters and other parasympathomimetic drugs. Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response."}
{"id": "PMID:17942", "title": "The outbreak of equine influenza in England: January 1976.", "content": "Equine influenza type 2 infections occurred in the Newmarket areas in January 1976. The disease did not spread to any extent and while this may have been due to recent vaccination it was found that not all vaccinated horses were fully protected. The virus involved showed some antigenic drift from the prototype strain A/equine/Miami/1/63 (Heq 2 Neq 2).", "contents": "The outbreak of equine influenza in England: January 1976. Equine influenza type 2 infections occurred in the Newmarket areas in January 1976. The disease did not spread to any extent and while this may have been due to recent vaccination it was found that not all vaccinated horses were fully protected. The virus involved showed some antigenic drift from the prototype strain A/equine/Miami/1/63 (Heq 2 Neq 2)."}
{"id": "PMID:17944", "title": "Aneurysms of the coronary arteries in infants and children. A review, and report of six cases.", "content": "In recent years large numbers of the so-called \"mucocutaneous lymph node syndrome\" or \"Kawasaki's disease\" have been described by Japanese workers, but instances of this disorder are only now being reported as isolated cases by European or North American physicians. The disease has, therefore, been considered to be a new entity. One of its most striking features is the development of aneurysms of the coronary arteries in infants or children, which may lead to sudden death. Aneurysms of the coronary arteries in childhood are rare, and hence it was considered relevant to report six such cases, and to examine their possible relationship to Kawasaki's disease. The pathological changes underlying the latter disorder are not well known; they are considered to be indistinguishable from infantile polyarteritis nodosa. A diagnosis of polyarteritis nodosa was also thought to be most likely to apply in the cases presented here, particularly in view of the frequency with which aneurysms of the coronary arteries have been found in this disorder. In the absence of valid pathological distinctions between Kawasaki's disease and infantile polyarteritis nodosa, the question arises whether these entities are, in fact, different, and whether Kawasaki's disease is the new entity it is assumed to be.", "contents": "Aneurysms of the coronary arteries in infants and children. A review, and report of six cases. In recent years large numbers of the so-called \"mucocutaneous lymph node syndrome\" or \"Kawasaki's disease\" have been described by Japanese workers, but instances of this disorder are only now being reported as isolated cases by European or North American physicians. The disease has, therefore, been considered to be a new entity. One of its most striking features is the development of aneurysms of the coronary arteries in infants or children, which may lead to sudden death. Aneurysms of the coronary arteries in childhood are rare, and hence it was considered relevant to report six such cases, and to examine their possible relationship to Kawasaki's disease. The pathological changes underlying the latter disorder are not well known; they are considered to be indistinguishable from infantile polyarteritis nodosa. A diagnosis of polyarteritis nodosa was also thought to be most likely to apply in the cases presented here, particularly in view of the frequency with which aneurysms of the coronary arteries have been found in this disorder. In the absence of valid pathological distinctions between Kawasaki's disease and infantile polyarteritis nodosa, the question arises whether these entities are, in fact, different, and whether Kawasaki's disease is the new entity it is assumed to be."}
{"id": "PMID:17945", "title": "[Cardiac output, blood gas analysis and the acid-base state of the blood in chronic cor pulmonale].", "content": "In 61 patients with chronic cor pulmonale with compensation and decompensation of circulation, the stroke and minute heart volume were studied as well as the indices, characterizing the blood-gas contents and acid-base blood state. The minute heart volume in the patients examined proved to be with normal values. Stroke heart volume is decreased in all patients examined with chronic cor pulmonale. The acceleration of heart activity enables the maintenance of normal minute volume. Hypoxemia has a cardiac depressive effect as regards minute volume and heart rate. The moderate hypercapnia has a certain stimulating effect on heart. A direct proportional correlation exists between the hypercapnia degree and the tendency of minute volume increase and especially of heart rate. The campaign against hypoxemia is an essential element in the prophylaxis and early treatment of chronic cor pulmonale.", "contents": "[Cardiac output, blood gas analysis and the acid-base state of the blood in chronic cor pulmonale]. In 61 patients with chronic cor pulmonale with compensation and decompensation of circulation, the stroke and minute heart volume were studied as well as the indices, characterizing the blood-gas contents and acid-base blood state. The minute heart volume in the patients examined proved to be with normal values. Stroke heart volume is decreased in all patients examined with chronic cor pulmonale. The acceleration of heart activity enables the maintenance of normal minute volume. Hypoxemia has a cardiac depressive effect as regards minute volume and heart rate. The moderate hypercapnia has a certain stimulating effect on heart. A direct proportional correlation exists between the hypercapnia degree and the tendency of minute volume increase and especially of heart rate. The campaign against hypoxemia is an essential element in the prophylaxis and early treatment of chronic cor pulmonale."}
{"id": "PMID:17947", "title": "A physician extender training program based on clinical algorithms.", "content": "The ability of physician extenders to provide patient care in a variety of settings has been reported widely. Less attention has been paid to training programs, especially those of short duration, for physician extenders. A three-month training program for physician extenders at a large teaching hospital was based on teaching the skills needed to run 39 clinical algorithms. The course content and the methods used to test the students during the three months may prove of value to those preparing similar programs.", "contents": "A physician extender training program based on clinical algorithms. The ability of physician extenders to provide patient care in a variety of settings has been reported widely. Less attention has been paid to training programs, especially those of short duration, for physician extenders. A three-month training program for physician extenders at a large teaching hospital was based on teaching the skills needed to run 39 clinical algorithms. The course content and the methods used to test the students during the three months may prove of value to those preparing similar programs."}
{"id": "PMID:17948", "title": "[Aspartate transfer across the blood-retina barrier (author's transl)].", "content": "Permeability of the blood-brain barrier is restricted with respect to amino acids involved in neurotransmission. This finding is well-documented in the case of gamma-amino-butyric acid (GABA) and glycine. Aspartic acid, which is also considered to be a transmitter, equally does not cross the blood-brain barrier in the rat with ease. This amino acid is also thought to be a transmitter in the retina. In order to examine the permeability of the blood-retina barrier with respect to aspartic acid, and investigation was undertaken of the effect of asparate on the light-induced sum potential of the retina in the isolated, perfused cat eyeball, a preparation which guarantees intact retinal circulation. The findings were compared with findings in the isolated retina where the substance was brought into direct contact with the retinal neurons. It was found that aspartate crossed the vascular barrier only to a limited extent and with delay. These results support the hypothesis that aspartic acid is involved in the retinal information processing.", "contents": "[Aspartate transfer across the blood-retina barrier (author's transl)]. Permeability of the blood-brain barrier is restricted with respect to amino acids involved in neurotransmission. This finding is well-documented in the case of gamma-amino-butyric acid (GABA) and glycine. Aspartic acid, which is also considered to be a transmitter, equally does not cross the blood-brain barrier in the rat with ease. This amino acid is also thought to be a transmitter in the retina. In order to examine the permeability of the blood-retina barrier with respect to aspartic acid, and investigation was undertaken of the effect of asparate on the light-induced sum potential of the retina in the isolated, perfused cat eyeball, a preparation which guarantees intact retinal circulation. The findings were compared with findings in the isolated retina where the substance was brought into direct contact with the retinal neurons. It was found that aspartate crossed the vascular barrier only to a limited extent and with delay. These results support the hypothesis that aspartic acid is involved in the retinal information processing."}
{"id": "PMID:17949", "title": "[Recent concepts of respiratory regulation (author's transl)].", "content": "There are two functional aspects of the respiratory control system, the one being adaptation of ventilation to metabolic needs and the other acid-base homeostasis of the extracellular fluid of the brain. These two functions are perfectly compatible with one another under normal conditions. During hypoxia or hyperthermia, however, a compromise has to be reaches by the system between securing oxygen availability or homeothermy, respectively and acid-base homeostasis of the brain. The control system works with tonic chemosensitive and non-chemosensitive neural input of action potentials to the centres. The centres, either by indigenous mechanisms or by phasic reflex input from the stretch receptors of the lungs or phasic feedback mechanisms from the pontine pneumotaxic centre, modulate the tonic impulse input into the rhythmic output to the respiratory muscles. Recent observations on this \"inspiratory off switch mechanism\" are discussed. Chemosensitive sensors are found in the carotid and aortic glomera responding to low pO2 and, additionally, to pH and pCO2 and in central chemosensitive structures on the ventral side of the medulla oblongata, responding mainly to changes in local hydrogen ion concentration. The proprioceptive reflexes in the sense of a gamma loop improve the performance of the system if additional flow resistance must be overcome. In metabolic and respiratory acidosis-alkalosis the kidney either plays a compensatory role or serves to restore normal conditions. The maternal hormones in pregnancy effect air improvement in CO2 output of the fetus.", "contents": "[Recent concepts of respiratory regulation (author's transl)]. There are two functional aspects of the respiratory control system, the one being adaptation of ventilation to metabolic needs and the other acid-base homeostasis of the extracellular fluid of the brain. These two functions are perfectly compatible with one another under normal conditions. During hypoxia or hyperthermia, however, a compromise has to be reaches by the system between securing oxygen availability or homeothermy, respectively and acid-base homeostasis of the brain. The control system works with tonic chemosensitive and non-chemosensitive neural input of action potentials to the centres. The centres, either by indigenous mechanisms or by phasic reflex input from the stretch receptors of the lungs or phasic feedback mechanisms from the pontine pneumotaxic centre, modulate the tonic impulse input into the rhythmic output to the respiratory muscles. Recent observations on this \"inspiratory off switch mechanism\" are discussed. Chemosensitive sensors are found in the carotid and aortic glomera responding to low pO2 and, additionally, to pH and pCO2 and in central chemosensitive structures on the ventral side of the medulla oblongata, responding mainly to changes in local hydrogen ion concentration. The proprioceptive reflexes in the sense of a gamma loop improve the performance of the system if additional flow resistance must be overcome. In metabolic and respiratory acidosis-alkalosis the kidney either plays a compensatory role or serves to restore normal conditions. The maternal hormones in pregnancy effect air improvement in CO2 output of the fetus."}
{"id": "PMID:17951", "title": "[Bistability in the activity of glutamine synthetase in ammonium-limiting chemostat cultures of Escherichia coli ML 30].", "content": "The approximative estimation of the function micron([NH+4]) in cultures of E. coli ML 30 had shown that bistability of the ammonium concentration in ammonium limited continuous cultures could be possible (BERGTER et al. 1977). This phenomenon suggested a bistability in the regulation of ammonia assimilation. Therefore, the activity of one key enzyme of the two ammonia assimilation systems was measured. The distribution of the activity of glutamine synthetase in ammonia limited continuous cultures after different transition states confirmed this suggestion.", "contents": "[Bistability in the activity of glutamine synthetase in ammonium-limiting chemostat cultures of Escherichia coli ML 30]. The approximative estimation of the function micron([NH+4]) in cultures of E. coli ML 30 had shown that bistability of the ammonium concentration in ammonium limited continuous cultures could be possible (BERGTER et al. 1977). This phenomenon suggested a bistability in the regulation of ammonia assimilation. Therefore, the activity of one key enzyme of the two ammonia assimilation systems was measured. The distribution of the activity of glutamine synthetase in ammonia limited continuous cultures after different transition states confirmed this suggestion."}
{"id": "PMID:17957", "title": "[The problems of adverse effects to the liver of alpha-methyldopa].", "content": "In 20 patients who were treated with alpha-methyldopa since at least one year the bilirubin content, the activities of aspartate and alanine-aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well as the retention of bromsulphalein were determined. In altogether 10 patients pathological findings of laboratory examinations were the result. The gamma-glutamyl transpeptidase activity proved to be particularly sensitive. By means of biopsy in 3 of these patients a fatty degeneration of the liver in stage I and in 4 of them a fatty degeneration of the parenchyma cell of minor degree were proved. A connection between duration and dosage of the treatment with alpha-methyldopa and these hepatological findings could not be ascertained statistically.", "contents": "[The problems of adverse effects to the liver of alpha-methyldopa]. In 20 patients who were treated with alpha-methyldopa since at least one year the bilirubin content, the activities of aspartate and alanine-aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well as the retention of bromsulphalein were determined. In altogether 10 patients pathological findings of laboratory examinations were the result. The gamma-glutamyl transpeptidase activity proved to be particularly sensitive. By means of biopsy in 3 of these patients a fatty degeneration of the liver in stage I and in 4 of them a fatty degeneration of the parenchyma cell of minor degree were proved. A connection between duration and dosage of the treatment with alpha-methyldopa and these hepatological findings could not be ascertained statistically."}
{"id": "PMID:17963", "title": "[Relationship between thermal treatment of milk and hysteresis of the milk protein system. II. Studies on casein micelles (author's transl)].", "content": "The association of colloidal calcium phosphate with the casein micelles is the principal reason for hysteresis of the milk protein system. Because of this association the secondary calcium phosphate cannot be titrated at its pK = 7.2, but only at lower pH values depending on the previous thermal treatment of the milk. However after overcoming certain energy barriers it can be titrated (between pH 5.8 and 5.2), but then calcium phosphate is separated irreversibly from the micelles. Therefore in the subsequent base titration other molecular conditions are passed through than in acid titration. The consequence is a hysteresislike titration curve. By heating, the surface of the micelles are covered successively with serum proteins. Due to this coating additional diffusion barriers are constructed. The diffusion of the protons into the interior of the micelles is measurably retarded. The expansion of the hysteresis loop can be determined quantitatively.", "contents": "[Relationship between thermal treatment of milk and hysteresis of the milk protein system. II. Studies on casein micelles (author's transl)]. The association of colloidal calcium phosphate with the casein micelles is the principal reason for hysteresis of the milk protein system. Because of this association the secondary calcium phosphate cannot be titrated at its pK = 7.2, but only at lower pH values depending on the previous thermal treatment of the milk. However after overcoming certain energy barriers it can be titrated (between pH 5.8 and 5.2), but then calcium phosphate is separated irreversibly from the micelles. Therefore in the subsequent base titration other molecular conditions are passed through than in acid titration. The consequence is a hysteresislike titration curve. By heating, the surface of the micelles are covered successively with serum proteins. Due to this coating additional diffusion barriers are constructed. The diffusion of the protons into the interior of the micelles is measurably retarded. The expansion of the hysteresis loop can be determined quantitatively."}
{"id": "PMID:17958", "title": "Regulation and characterization of L-serine: pyruvate aminotransferase in rat liver cytosol and mitochondria.", "content": "Distribution of rat liver serine: pyruvate aminotransferase between cytosol and mitochondria varies considerably with the dietary and hormonal state of animals. Feeding a high-protein diet or fasting the animals results in an increase in the enzyme activity of both fractions but more marked in the mitochondrial fraction. A low-protein diet exerts the reverse effect. A single administration of dibutyryl cyclic AMP causes a rapid elevation of the enzyme activity in both fractions, which is effectively prevented by cycloheximide, actinomycin D and cortisone. The activity in mitochondria increases with a lag of 2 h following injection of the nucleotide inducer, in contrast to the cytosol enzyme, which increases without any lag. Gel filtration and DEAE cellulose chromatography of the enzyme from both fractions revealed the similar pattern and some kinetic constants of these two types of the enzyme were not significantly different from each other. These results indicate that rat liver serine: pyruvate aminotransferase is synthesized in the extra-mitochondrial site and transfered to mitochondria.", "contents": "Regulation and characterization of L-serine: pyruvate aminotransferase in rat liver cytosol and mitochondria. Distribution of rat liver serine: pyruvate aminotransferase between cytosol and mitochondria varies considerably with the dietary and hormonal state of animals. Feeding a high-protein diet or fasting the animals results in an increase in the enzyme activity of both fractions but more marked in the mitochondrial fraction. A low-protein diet exerts the reverse effect. A single administration of dibutyryl cyclic AMP causes a rapid elevation of the enzyme activity in both fractions, which is effectively prevented by cycloheximide, actinomycin D and cortisone. The activity in mitochondria increases with a lag of 2 h following injection of the nucleotide inducer, in contrast to the cytosol enzyme, which increases without any lag. Gel filtration and DEAE cellulose chromatography of the enzyme from both fractions revealed the similar pattern and some kinetic constants of these two types of the enzyme were not significantly different from each other. These results indicate that rat liver serine: pyruvate aminotransferase is synthesized in the extra-mitochondrial site and transfered to mitochondria."}
{"id": "PMID:17959", "title": "Identification of essential histidine residues of aminoacylase by photooxidation and by reaction with diethylpyrocarbonate.", "content": "State and function of the histidine residues of aminoacylase were investigated by photoxidation in the presence of methylene blue and by chemical modification with diethylpyrocarbonate. Complete inactivation of the enzyme was observed after oxidation of 4 histidine residues. From the pH dependence of the photooxidation it becomes evident that the inactivation of the enzyme is not a consequence of the simultaneous oxidation of tryptophan residues. The enzyme is also inactivated by chemical modification of histidine residues with diethylpyrocarbonate. Activity is restored by treatment with hydroxylamine. Zn2+-ions which are essential for the activity of aminoacylase protect the available histidine molecules against photooxidation and attack by diethylpyrocarbonate. It is suggested that histidine is involved in the binding of the essential Zn2+-ions.", "contents": "Identification of essential histidine residues of aminoacylase by photooxidation and by reaction with diethylpyrocarbonate. State and function of the histidine residues of aminoacylase were investigated by photoxidation in the presence of methylene blue and by chemical modification with diethylpyrocarbonate. Complete inactivation of the enzyme was observed after oxidation of 4 histidine residues. From the pH dependence of the photooxidation it becomes evident that the inactivation of the enzyme is not a consequence of the simultaneous oxidation of tryptophan residues. The enzyme is also inactivated by chemical modification of histidine residues with diethylpyrocarbonate. Activity is restored by treatment with hydroxylamine. Zn2+-ions which are essential for the activity of aminoacylase protect the available histidine molecules against photooxidation and attack by diethylpyrocarbonate. It is suggested that histidine is involved in the binding of the essential Zn2+-ions."}
{"id": "PMID:17964", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VII. Influence of sodium chloride on the tripolyphosphatase and diphosphatase activity in bovine muscle (author's transl)].", "content": "Sodium chloride activates the tripolyphosphatase of the muscle tissue. Optimum activity occurs at 4--5 percent NaC1. The increase in activity seems to be due to the effect of C1-ions. NaC1 inhibits the tripolyphosphatase activity of muscle press juice. NaC1 decreases the total diphosphatase activity of muscle tissue as well as the diphosphatase activity of muscle press juice. Addition of NaC1 to pre-rigor muscle increases the ultimate pH value (post-rigor-muscle) and, consequently, causes a lower tripolyphosphatase activity and a higher diphosphatase activity than is observed, when NaC1 is added to the post-rigor muscle.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VII. Influence of sodium chloride on the tripolyphosphatase and diphosphatase activity in bovine muscle (author's transl)]. Sodium chloride activates the tripolyphosphatase of the muscle tissue. Optimum activity occurs at 4--5 percent NaC1. The increase in activity seems to be due to the effect of C1-ions. NaC1 inhibits the tripolyphosphatase activity of muscle press juice. NaC1 decreases the total diphosphatase activity of muscle tissue as well as the diphosphatase activity of muscle press juice. Addition of NaC1 to pre-rigor muscle increases the ultimate pH value (post-rigor-muscle) and, consequently, causes a lower tripolyphosphatase activity and a higher diphosphatase activity than is observed, when NaC1 is added to the post-rigor muscle."}
{"id": "PMID:17965", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VIII. Influence of divalent cations on the tripolyphosphatase activity of muscle tissue (author's transl)].", "content": "The tripolyphosphatase of comminuted muscle tissue is activated by MgC1(2) and ethylenediamine tetraacetate and inhibited by CaC1(2) and diphosphate. These results are discussed with reference to the formation of an inactive enzyme-substrate complex.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VIII. Influence of divalent cations on the tripolyphosphatase activity of muscle tissue (author's transl)]. The tripolyphosphatase of comminuted muscle tissue is activated by MgC1(2) and ethylenediamine tetraacetate and inhibited by CaC1(2) and diphosphate. These results are discussed with reference to the formation of an inactive enzyme-substrate complex."}
{"id": "PMID:17983", "title": "Factors influencing L-asparaginase production by staphylococci.", "content": "Cultural and nutritional requirements for a maximum synthesis of 1-asparaginase by staphylococci were determined. The best production of the enzyme was found in the stationary phase of growth of a batch culture. The highest 1-asparaginase yield was obtained when the culture were aerated during an exponential phase of growth and further incubated in the stationary phase. Optimum pH for the enzyme production was 7.5. Glucose inhibited the enzyme formation. Maximum yield of 1-asparaginase was obtained when casein hydrolysate and yeast extract were supplied as carbon and nitrogen sources. Repression by 1-asparagine and 1-aspartic acid was absent.", "contents": "Factors influencing L-asparaginase production by staphylococci. Cultural and nutritional requirements for a maximum synthesis of 1-asparaginase by staphylococci were determined. The best production of the enzyme was found in the stationary phase of growth of a batch culture. The highest 1-asparaginase yield was obtained when the culture were aerated during an exponential phase of growth and further incubated in the stationary phase. Optimum pH for the enzyme production was 7.5. Glucose inhibited the enzyme formation. Maximum yield of 1-asparaginase was obtained when casein hydrolysate and yeast extract were supplied as carbon and nitrogen sources. Repression by 1-asparagine and 1-aspartic acid was absent."}
{"id": "PMID:17984", "title": "Subcellular distribution and properties of alkaline inorganic pyrophosphatase of maize leaves.", "content": "1. Studies on the distribution of alkaline inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) in the subcellular fractions of maize leaves showed that the enzyme is present in cytoplasm, chloroplasts and mitochondria. The activity observed in nuclei and microsomes may result from contamination with the mitochondrial fraction. 2. Alkaline pyrophosphatases from three subcellular fractions were purified by fractionation with (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography, and by isoelectric focusing. Highly purified enzyme preparations, with specific activities ranging from 55 to 188 micronmoles/min/mg protein, were obtained. 3. All the enzymes exhibited the maximum activity at pH 8.5 and the Mg2+/PPi ratio of 5. They differed in electrophoretic mobility, pI, and susceptibility to urea and thermal denaturation. This indicates that they represent isoenzymes compartmentized in particular subcellular fractions.", "contents": "Subcellular distribution and properties of alkaline inorganic pyrophosphatase of maize leaves. 1. Studies on the distribution of alkaline inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) in the subcellular fractions of maize leaves showed that the enzyme is present in cytoplasm, chloroplasts and mitochondria. The activity observed in nuclei and microsomes may result from contamination with the mitochondrial fraction. 2. Alkaline pyrophosphatases from three subcellular fractions were purified by fractionation with (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography, and by isoelectric focusing. Highly purified enzyme preparations, with specific activities ranging from 55 to 188 micronmoles/min/mg protein, were obtained. 3. All the enzymes exhibited the maximum activity at pH 8.5 and the Mg2+/PPi ratio of 5. They differed in electrophoretic mobility, pI, and susceptibility to urea and thermal denaturation. This indicates that they represent isoenzymes compartmentized in particular subcellular fractions."}
{"id": "PMID:17985", "title": "Acid phosphatase of the yeast Rhodotorula rubra. Purification and properties of the enzyme.", "content": "1. Acid phosphatase from the yeast Rhodotorula rubra was purified 44-fold. The purification procedure involved mechanical disruption of cells, precipitation with ethanol, chromatography on DEAE- and CM-cellulose. 2. The purified enzyme is homogeneous in polyacrylamide gels at pH 4.5, 9.5 and 8.4. Carbohydrate content accounts for 57% of the total weight. The optimum pH is at 4.0-4.6, and the enzyme is stable over pH range from 2.6 to 6.0. Full activity was retained on 60-min incubation at 50 degrees C, but it was reduced by half on 60-min incubation at 65 degrees C. 3. Specificity of the enzyme is fairly broad; monoesters of carbohydrates, and nucleosides and inorganic pyrophosphate can serve as substrates. Km was found to be 1 X 10(-4) M for p-nitrophenyl phosphate as a substrate. The enzyme is inhibited by molybdate, phosphate, arsenate and fluoride ions.", "contents": "Acid phosphatase of the yeast Rhodotorula rubra. Purification and properties of the enzyme. 1. Acid phosphatase from the yeast Rhodotorula rubra was purified 44-fold. The purification procedure involved mechanical disruption of cells, precipitation with ethanol, chromatography on DEAE- and CM-cellulose. 2. The purified enzyme is homogeneous in polyacrylamide gels at pH 4.5, 9.5 and 8.4. Carbohydrate content accounts for 57% of the total weight. The optimum pH is at 4.0-4.6, and the enzyme is stable over pH range from 2.6 to 6.0. Full activity was retained on 60-min incubation at 50 degrees C, but it was reduced by half on 60-min incubation at 65 degrees C. 3. Specificity of the enzyme is fairly broad; monoesters of carbohydrates, and nucleosides and inorganic pyrophosphate can serve as substrates. Km was found to be 1 X 10(-4) M for p-nitrophenyl phosphate as a substrate. The enzyme is inhibited by molybdate, phosphate, arsenate and fluoride ions."}
{"id": "PMID:17986", "title": "[Proof of guanylate cyclase activity in the coronary artery of cattle].", "content": "Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity.", "contents": "[Proof of guanylate cyclase activity in the coronary artery of cattle]. Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity."}
{"id": "PMID:17987", "title": "[Demonstration of protein kinase activities in the coronary artery of cattle].", "content": "Protein kinase activities were identified in a soluble and a particulate fraction from the A. coronaria of cattle. For both protein kinase activities Mg++ is essential. Protamine was used as a substrate of the protein kinase activity of the soluble fraction. The pH optimum of the protein kinase activity of the soluble fraction is around 6.5. The Km-value of the protein kinase for ATP is 1.9 +/- 0.4 - 10(-5) M. cAMP stimulates the protein kinase activity more effectively than cGMP. Ca++ cannot replace Mg++; monovalent cations (Na+ and K+) show no influence. The protein kinase activity of the fraction was determined via endogenous phosphorylation. By means of the cAMP-dependent particulate protein kinase 72 to 80 percent of the serine residues are phosphorylated. The pH optimum of the protein kinase activity of the particulate fraction lies around 7.0. The Km-value of the enzyme for ATP is 6.6 +/- 0.8 - 10(-5) M. cGMP stimulates the protein kinase of the particulate fraction better than cAMP. For the protein kinase activity of this fraction Ca++ replaces Mg++ in the endogenous phosphorylation but not in the exogenous phosphorylation (protamine). In the presence of Mg++ and in the additional presence of Na+ or K+, the protein kinase activity is suppressed in the endogenous phosphorylation whereas it is stimulated in the exogenous phosphorylation.", "contents": "[Demonstration of protein kinase activities in the coronary artery of cattle]. Protein kinase activities were identified in a soluble and a particulate fraction from the A. coronaria of cattle. For both protein kinase activities Mg++ is essential. Protamine was used as a substrate of the protein kinase activity of the soluble fraction. The pH optimum of the protein kinase activity of the soluble fraction is around 6.5. The Km-value of the protein kinase for ATP is 1.9 +/- 0.4 - 10(-5) M. cAMP stimulates the protein kinase activity more effectively than cGMP. Ca++ cannot replace Mg++; monovalent cations (Na+ and K+) show no influence. The protein kinase activity of the fraction was determined via endogenous phosphorylation. By means of the cAMP-dependent particulate protein kinase 72 to 80 percent of the serine residues are phosphorylated. The pH optimum of the protein kinase activity of the particulate fraction lies around 7.0. The Km-value of the enzyme for ATP is 6.6 +/- 0.8 - 10(-5) M. cGMP stimulates the protein kinase of the particulate fraction better than cAMP. For the protein kinase activity of this fraction Ca++ replaces Mg++ in the endogenous phosphorylation but not in the exogenous phosphorylation (protamine). In the presence of Mg++ and in the additional presence of Na+ or K+, the protein kinase activity is suppressed in the endogenous phosphorylation whereas it is stimulated in the exogenous phosphorylation."}
{"id": "PMID:17988", "title": "Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice.", "content": "The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested.", "contents": "Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice. The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested."}
{"id": "PMID:17989", "title": "[An ion exchange method to determine free metal concentrations, adapted for use in biological fluids: methods and determination of (Mg2+)].", "content": "An ion exchange method for measuring concentrations of free (ionized) metal ions and its application to the determination of [Mg2+] is described. A surface sulfonated polystyrene material is used as the \"twodimensional\" cation exchanger. The sample-volume is 1 ml. About 50 determinations can be performed within 1 hr having a standard error of +/- (2-4)% in the optimal range of measurement. Advantages and disadvantages of the method compared with other ones are demonstrated and discussed. Free Mg2+ ion concentrations were measured in solutions containing pyrophosphate as well as haemoglobin and compared with those which were determined by equilibrium calculation or ultrafiltration.", "contents": "[An ion exchange method to determine free metal concentrations, adapted for use in biological fluids: methods and determination of (Mg2+)]. An ion exchange method for measuring concentrations of free (ionized) metal ions and its application to the determination of [Mg2+] is described. A surface sulfonated polystyrene material is used as the \"twodimensional\" cation exchanger. The sample-volume is 1 ml. About 50 determinations can be performed within 1 hr having a standard error of +/- (2-4)% in the optimal range of measurement. Advantages and disadvantages of the method compared with other ones are demonstrated and discussed. Free Mg2+ ion concentrations were measured in solutions containing pyrophosphate as well as haemoglobin and compared with those which were determined by equilibrium calculation or ultrafiltration."}
{"id": "PMID:17990", "title": "Pulmonary complications, ventilation and blood gases after upper abdominal surgery.", "content": "Forty patients who underwent elective cholecystectomy were examined preoperatively and during the first postoperative week by physical examination, measurement of FVC and FEV1, arterial pH and blood gas analyses, and chest x-ray. Postoperative pulmonary complications (p.p.c.) were detected in 30 (75%) of the patients. Simple auscultation was the most sensitive tool in discovering p.p.c., but 18 of the 30 patients with complications also had a pathological chest x-ray. Obesity, smoking postoperative naso-gastric tube and postoperative wound infection were predisposing factors for p.p.c. Six patients with preoperative pulmonary disease all had a progress in their lung pathology. There was no definite relationship of duration of anaesthesia or drainage of the abdominal wound to development of p.p.c. The patients with p.p.c. showed a deeper and more prolonged fall in Pao2 postoperatively than the normal group. None of the normals showed an arterial Po2 below 70 mmHg in the postoperative course, while 63% of the p.p.c. group did. FVC and FEV1 showed marked reductions from preoperative values on the first postoperative day, and then gradually increased to near preoperative values after 1 week. Arterial pH and Pco2 showed no definite changes during the postoperative course.", "contents": "Pulmonary complications, ventilation and blood gases after upper abdominal surgery. Forty patients who underwent elective cholecystectomy were examined preoperatively and during the first postoperative week by physical examination, measurement of FVC and FEV1, arterial pH and blood gas analyses, and chest x-ray. Postoperative pulmonary complications (p.p.c.) were detected in 30 (75%) of the patients. Simple auscultation was the most sensitive tool in discovering p.p.c., but 18 of the 30 patients with complications also had a pathological chest x-ray. Obesity, smoking postoperative naso-gastric tube and postoperative wound infection were predisposing factors for p.p.c. Six patients with preoperative pulmonary disease all had a progress in their lung pathology. There was no definite relationship of duration of anaesthesia or drainage of the abdominal wound to development of p.p.c. The patients with p.p.c. showed a deeper and more prolonged fall in Pao2 postoperatively than the normal group. None of the normals showed an arterial Po2 below 70 mmHg in the postoperative course, while 63% of the p.p.c. group did. FVC and FEV1 showed marked reductions from preoperative values on the first postoperative day, and then gradually increased to near preoperative values after 1 week. Arterial pH and Pco2 showed no definite changes during the postoperative course."}
{"id": "PMID:17991", "title": "The cerebrovascular CO2 reactivity during the acute phase of brain injury.", "content": "Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed.", "contents": "The cerebrovascular CO2 reactivity during the acute phase of brain injury. Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed."}
{"id": "PMID:17992", "title": "The pressure-flow relations of the canine brain in acute mechanically induced arterial hypertension at different levels of cerebral blood flow.", "content": "Cerebral pressure-flow relations were studied in anaesthetized dogs during acute arterial hypertension, induced by compression of the thoracic aorta. In one group of animals steady state measurements were made with the radioactive gas elimination method. In another group the immediate changes of blood flow at a blood pressure change, as indicated by variations in the cerebral venous oxygen saturation, were studied with continuous oximetric analyses of the superior sagittal sinus blood. The initial blood flow was varied by variations of the arterial carbon dioxide tension of injections of papaverine. At low or normal blood flows autoregulation was efficient up to pressures around 180-200 mmHg, while at higher flows the upper autoregulatory pressure limit was found at lower blood pressures. Above the autoregulatory limit-irrespective of the control flow level-there was a rise in blood flow and a decrease in cerebrovascular resistance.", "contents": "The pressure-flow relations of the canine brain in acute mechanically induced arterial hypertension at different levels of cerebral blood flow. Cerebral pressure-flow relations were studied in anaesthetized dogs during acute arterial hypertension, induced by compression of the thoracic aorta. In one group of animals steady state measurements were made with the radioactive gas elimination method. In another group the immediate changes of blood flow at a blood pressure change, as indicated by variations in the cerebral venous oxygen saturation, were studied with continuous oximetric analyses of the superior sagittal sinus blood. The initial blood flow was varied by variations of the arterial carbon dioxide tension of injections of papaverine. At low or normal blood flows autoregulation was efficient up to pressures around 180-200 mmHg, while at higher flows the upper autoregulatory pressure limit was found at lower blood pressures. Above the autoregulatory limit-irrespective of the control flow level-there was a rise in blood flow and a decrease in cerebrovascular resistance."}
{"id": "PMID:17993", "title": "Peroperative arterial blood pressure control in ophthalmological anaesthesia.", "content": "The effects were studied of a standardised general anaesthesia on mean arterial blood pressure, central venous pressure, blood gas values and the course of cataract operations. The material consisted of 20 unselected senile cataract operations, the mean age of the patients being 71.3 years. The arterial blood pressure was continuously checked, using an intra-arterial cannula. In order to avoid vitreous loss, the blood pressure was successfully kept optimally low during the extraction of the lens. No vitreous problems were noted. The oxygenation and ventilation of the patients were sufficient during anaesthesia and immediately postoperatively.", "contents": "Peroperative arterial blood pressure control in ophthalmological anaesthesia. The effects were studied of a standardised general anaesthesia on mean arterial blood pressure, central venous pressure, blood gas values and the course of cataract operations. The material consisted of 20 unselected senile cataract operations, the mean age of the patients being 71.3 years. The arterial blood pressure was continuously checked, using an intra-arterial cannula. In order to avoid vitreous loss, the blood pressure was successfully kept optimally low during the extraction of the lens. No vitreous problems were noted. The oxygenation and ventilation of the patients were sufficient during anaesthesia and immediately postoperatively."}
{"id": "PMID:17994", "title": "Effects upon the fetus of oxygen administration to the mother. A study in monkey.", "content": "Catheters were placed into assorted arteries and veins of 8 anaesthetized pregnant monkeys and their fetuses. Oxygen-sensitive electrodes were also inserted subcutaneously into 3 of the 8 fetuses. Periodic samples of maternal and fetal blood were analyzed for PO2, PCO2 and pH. Oxygen administration to the mothers reliably increased the PO2 of blood taken from the fetal carotid artery and less constantly augmented the PO2 of blood withdrawn from the femoral artery and vein. During 5-6 hours of study the oxygen tension of fetal blood samples of all animals progressively declined. However, the most marked declines in PO2 values at all fetal sites were regularly observed at those times as--or after--the mothers emerged from anaesthesia. At these times also the magnitudes of the increases in fetal blood PO2 brought about by administering oxygen to the mothers diminished markedly and in parallel at all sample sites. The closely similar magnitudes of these various reductions at all fetal sample sties indicate that the basic mechanisms leading to decreased oxygen delivery lie outside the fetuses and are most likely due to decreased maternal blood flow to the uterus because of increased maternal sympathetic stimulation. These reductions in oxygen delivery to the fetus are all regularly reversed by reanasthetizing the mothers. The studies carried out with oxygen-sensitive electrodes demonstrate that administering oxygen to the mothers regularly increases oxygen tension of fetal tissues but after a 50 sec delay.", "contents": "Effects upon the fetus of oxygen administration to the mother. A study in monkey. Catheters were placed into assorted arteries and veins of 8 anaesthetized pregnant monkeys and their fetuses. Oxygen-sensitive electrodes were also inserted subcutaneously into 3 of the 8 fetuses. Periodic samples of maternal and fetal blood were analyzed for PO2, PCO2 and pH. Oxygen administration to the mothers reliably increased the PO2 of blood taken from the fetal carotid artery and less constantly augmented the PO2 of blood withdrawn from the femoral artery and vein. During 5-6 hours of study the oxygen tension of fetal blood samples of all animals progressively declined. However, the most marked declines in PO2 values at all fetal sites were regularly observed at those times as--or after--the mothers emerged from anaesthesia. At these times also the magnitudes of the increases in fetal blood PO2 brought about by administering oxygen to the mothers diminished markedly and in parallel at all sample sites. The closely similar magnitudes of these various reductions at all fetal sample sties indicate that the basic mechanisms leading to decreased oxygen delivery lie outside the fetuses and are most likely due to decreased maternal blood flow to the uterus because of increased maternal sympathetic stimulation. These reductions in oxygen delivery to the fetus are all regularly reversed by reanasthetizing the mothers. The studies carried out with oxygen-sensitive electrodes demonstrate that administering oxygen to the mothers regularly increases oxygen tension of fetal tissues but after a 50 sec delay."}
{"id": "PMID:17995", "title": "The finding that secretory component is not associated with gamma-glutamyltranspeptidase activity.", "content": "The gamma-glutamyltranspeptidase activity of human milk was concentrated by ammonium sulphate precipitation. On gel chromatography of the dissolved precipitate, the activity was eluted in the high-molecular-weight fraction containing secretory IgA, while no activity appeared in the eluate at the position of free secretory component. Various antisera were added to portions of the pool of active fractions. No change of gamma-glutamyltranspeptidase activity appearedse activity was obtained with antisera against either IgA, secretory IgA or secretory component, while a large reduction of activity was seen with anti-human colostrum. Finally, purified free secretory component, secretory IgA and in vitro complexes between secretory component and IgA dimers were shown to be inactive in the gamma-glutamltranspeptidase assay, both in the absence and presence of zinc ions. Thus secretory component, either when free or bound to IgA, does not exhibit gamma-glutamyltranspeptidase activity, and therefore cannot function as such an enzyme in the transport of IgA across mucous membranes, as has been suggested previously.", "contents": "The finding that secretory component is not associated with gamma-glutamyltranspeptidase activity. The gamma-glutamyltranspeptidase activity of human milk was concentrated by ammonium sulphate precipitation. On gel chromatography of the dissolved precipitate, the activity was eluted in the high-molecular-weight fraction containing secretory IgA, while no activity appeared in the eluate at the position of free secretory component. Various antisera were added to portions of the pool of active fractions. No change of gamma-glutamyltranspeptidase activity appearedse activity was obtained with antisera against either IgA, secretory IgA or secretory component, while a large reduction of activity was seen with anti-human colostrum. Finally, purified free secretory component, secretory IgA and in vitro complexes between secretory component and IgA dimers were shown to be inactive in the gamma-glutamltranspeptidase assay, both in the absence and presence of zinc ions. Thus secretory component, either when free or bound to IgA, does not exhibit gamma-glutamyltranspeptidase activity, and therefore cannot function as such an enzyme in the transport of IgA across mucous membranes, as has been suggested previously."}
{"id": "PMID:17996", "title": "Atenolol in the treatment of angina pectoris.", "content": "Nineteen men, aged 41-64 years, with stable angina pectoris have completed a random double-blind study of atenolol, 50 mg b.i.d., atenolol, 100 mg b.i.d., and placebo. Fifteen patients had subjective improvement on atenolol, two were unchanged and two felt worse (because of asthenia/leg fatigue). No significant placebo effect was found. On both atenolol dosages there were highly significant reductions in heart rate at rest and during exercise and in BP. Only the maximal heart rate decreased significantly more on 100 mg atenolol than on 50 mg (p less than 0.01). Fourteen patients had the same or a better physical performance on the 50 mg b.i.d. regimen than on the 100 mg b.i.d. regimen, although this difference was not significant. Sixteen patients had higher bicycle exercise performance on atenolol than on placebo. Disregarding the three non-responders, a mean increase of 44% in bicycle performance was found. No serious side-effects were seen. Most individuals reported an increased feeling of well-being on atenolol.", "contents": "Atenolol in the treatment of angina pectoris. Nineteen men, aged 41-64 years, with stable angina pectoris have completed a random double-blind study of atenolol, 50 mg b.i.d., atenolol, 100 mg b.i.d., and placebo. Fifteen patients had subjective improvement on atenolol, two were unchanged and two felt worse (because of asthenia/leg fatigue). No significant placebo effect was found. On both atenolol dosages there were highly significant reductions in heart rate at rest and during exercise and in BP. Only the maximal heart rate decreased significantly more on 100 mg atenolol than on 50 mg (p less than 0.01). Fourteen patients had the same or a better physical performance on the 50 mg b.i.d. regimen than on the 100 mg b.i.d. regimen, although this difference was not significant. Sixteen patients had higher bicycle exercise performance on atenolol than on placebo. Disregarding the three non-responders, a mean increase of 44% in bicycle performance was found. No serious side-effects were seen. Most individuals reported an increased feeling of well-being on atenolol."}
{"id": "PMID:18002", "title": "Acute myocardial infarction and ischemic injury during surgery for coronary artery disease.", "content": "The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal mammary implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury in combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs.", "contents": "Acute myocardial infarction and ischemic injury during surgery for coronary artery disease. The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal mammary implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury in combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs."}
{"id": "PMID:18003", "title": "Isolated coronary periarteritis: report of a case of unexpected death in a young pregnant woman.", "content": "A case of sudden unexpected death in a 23 year old woman in her 8th month of pregnancy is reported. Death occurred from isolated coronary periarteritis with thrombosis. It is believed that the thrombosis was secondary to the adventitial infiltrate, which was of a type suggesting a hypersensitivity factor. It is proposed that pathogenetically this case is identical to reported cases of dissecting hemorrhage or aneurysm of the coronary artery and represents an entity different from other forms of inflammatory coronary disease.", "contents": "Isolated coronary periarteritis: report of a case of unexpected death in a young pregnant woman. A case of sudden unexpected death in a 23 year old woman in her 8th month of pregnancy is reported. Death occurred from isolated coronary periarteritis with thrombosis. It is believed that the thrombosis was secondary to the adventitial infiltrate, which was of a type suggesting a hypersensitivity factor. It is proposed that pathogenetically this case is identical to reported cases of dissecting hemorrhage or aneurysm of the coronary artery and represents an entity different from other forms of inflammatory coronary disease."}
{"id": "PMID:18004", "title": "An isozyme of erythrocyte pyruvate kinase (PK-Los Angeles) with impaired kinetics corrected by fructose-1, 6-diphosphate.", "content": "A mutant isozyme of erythrocyte pyruvate kinase was found in a family of French-Canadian ancestry in association with hemolytic anemia. The isozyme was characterized by normal maximal activity, pH optimum, heat stability, and fructosediphosphate activation constants, but had markedly reduced affinity for the substrate, phosphoenolpyruvate. This kinetic defect was corrected almost entirely in vitro by low concentrations of fructosediphosphate.", "contents": "An isozyme of erythrocyte pyruvate kinase (PK-Los Angeles) with impaired kinetics corrected by fructose-1, 6-diphosphate. A mutant isozyme of erythrocyte pyruvate kinase was found in a family of French-Canadian ancestry in association with hemolytic anemia. The isozyme was characterized by normal maximal activity, pH optimum, heat stability, and fructosediphosphate activation constants, but had markedly reduced affinity for the substrate, phosphoenolpyruvate. This kinetic defect was corrected almost entirely in vitro by low concentrations of fructosediphosphate."}
{"id": "PMID:18005", "title": "Bacteremia in hospitalized children.", "content": "The results of 6,951 blood cultures taken from hospitalized children are reviewed. One or more organisms grew from 6% (399) of the cultures, of which 189 (two thirds) were considered to represent confirmed bacteremia. The most common organisms associated with bacteremia were Haemophilus influenzae, Streptococcus pneumoniae, enterobacteriaceae, and Staphylococcus aureus. Patients with deficient host defenses (newborns, oncology patients) with bacteremia had a higher mortality than normal children. Laboratory techniques allowing more rapid detection of positive blood cultures resulted in major alterations in therapy in almost one half of all bacteremic patients.", "contents": "Bacteremia in hospitalized children. The results of 6,951 blood cultures taken from hospitalized children are reviewed. One or more organisms grew from 6% (399) of the cultures, of which 189 (two thirds) were considered to represent confirmed bacteremia. The most common organisms associated with bacteremia were Haemophilus influenzae, Streptococcus pneumoniae, enterobacteriaceae, and Staphylococcus aureus. Patients with deficient host defenses (newborns, oncology patients) with bacteremia had a higher mortality than normal children. Laboratory techniques allowing more rapid detection of positive blood cultures resulted in major alterations in therapy in almost one half of all bacteremic patients."}
{"id": "PMID:18007", "title": "Effects of cimetidine, a histamine H2-receptor antagonist, on various experimental gastric and duodenal ulcers.", "content": "The effects of cimetidine, a new histamine H2-receptor antagonist, on the development of experimental gastric and duodenal ulcers were studied. It was found that either by the oral, intraduodenal, or intraperitoneal route this agent had a marked inhibitory activity on stress-, aspirin-, indomethacin-, or histamine-induced gastric ulcers in rats and guinea pigs. The effects of cimetidine on stress-, aspirin-, and indomethacin-induced gastric ulcers were dose-dependent in many cases. Pylorus-ligation uclers, reserpine- or serotonin-induced gastric ulcers were little influenced by cimetidine. Duodenal ulcers induced by continuous infusion of carbachol-histamine were significantly inhibited by a simultaneous infusion of cimetidine. An analysis of gastric contents in pylorus-ligated rats after stressing indicated a decreased volume and acid output as the result of intraduodenal cimetidine treatment. In contrast, cimetidine exerted little influence on gastric secretion in rats treated with aspirin or in guinea pigs treated with histamine. Thus, the mechanism of action of cimetidine in preventing gastric or duodenal ulcers is likely to occur by suppression of gastric secretory function in a duodenal ulcer model but by suppression of other unknown ulcerogenic factors in gastric ulcer models.", "contents": "Effects of cimetidine, a histamine H2-receptor antagonist, on various experimental gastric and duodenal ulcers. The effects of cimetidine, a new histamine H2-receptor antagonist, on the development of experimental gastric and duodenal ulcers were studied. It was found that either by the oral, intraduodenal, or intraperitoneal route this agent had a marked inhibitory activity on stress-, aspirin-, indomethacin-, or histamine-induced gastric ulcers in rats and guinea pigs. The effects of cimetidine on stress-, aspirin-, and indomethacin-induced gastric ulcers were dose-dependent in many cases. Pylorus-ligation uclers, reserpine- or serotonin-induced gastric ulcers were little influenced by cimetidine. Duodenal ulcers induced by continuous infusion of carbachol-histamine were significantly inhibited by a simultaneous infusion of cimetidine. An analysis of gastric contents in pylorus-ligated rats after stressing indicated a decreased volume and acid output as the result of intraduodenal cimetidine treatment. In contrast, cimetidine exerted little influence on gastric secretion in rats treated with aspirin or in guinea pigs treated with histamine. Thus, the mechanism of action of cimetidine in preventing gastric or duodenal ulcers is likely to occur by suppression of gastric secretory function in a duodenal ulcer model but by suppression of other unknown ulcerogenic factors in gastric ulcer models."}
{"id": "PMID:18008", "title": "Quantitative determination of four antihistamines in combination by high-pressure liquid chromatography.", "content": "A procedure used to assay four antihistamines--brompheniramine maleate, chlorpheniramine maleate, pheniramine maleate and pyrilamine maleate in combination--is discussed. The method requires a high-pressure liquid chromatograph and an intermediate polarity column. The method is accurate and appears to be stability-indicating. The four antihistamines can be separated and assayed accurately. There is no interference from the two commonly used decongestants, phenylephrine hydrochloride and phenylpropanolamine hydrochloride, from the expectorant potassium guaiacolsulfonate, from the preservative propyl paraben or from two other antihistamines, diphenhydramine hydrochloride and bromdiphenhydramine hydrochloride. Guaifenesin, methylparaben and sodium benzoate interfere only with pheniramine maleate. Methapyrilene hydrochloride interferes only with pyrilamine maleate.", "contents": "Quantitative determination of four antihistamines in combination by high-pressure liquid chromatography. A procedure used to assay four antihistamines--brompheniramine maleate, chlorpheniramine maleate, pheniramine maleate and pyrilamine maleate in combination--is discussed. The method requires a high-pressure liquid chromatograph and an intermediate polarity column. The method is accurate and appears to be stability-indicating. The four antihistamines can be separated and assayed accurately. There is no interference from the two commonly used decongestants, phenylephrine hydrochloride and phenylpropanolamine hydrochloride, from the expectorant potassium guaiacolsulfonate, from the preservative propyl paraben or from two other antihistamines, diphenhydramine hydrochloride and bromdiphenhydramine hydrochloride. Guaifenesin, methylparaben and sodium benzoate interfere only with pheniramine maleate. Methapyrilene hydrochloride interferes only with pyrilamine maleate."}
{"id": "PMID:18009", "title": "Bladder dysfunction after radical abdominal hysterectomy.", "content": "Bladder dysfunction is a common occurrence following radical hysterectomy. We studied bladder function prospectively in 10 patients before and after radical hysterectomy. Results suggest that the hypertonic phase observed immediately postoperatively is the result of an increase in myogenic tonicity of the detrusor muscle secondary to the trauma of operation and prolonged catheter drainage. The inability of patients to urinate effectively is due to partial detrusor denervation. Combined cystometry and electromyography confirmed the presence of normal sphincter function and the absence of detrusor sphincter dyssynergia. Prevention of postoperative bladder atony includes a careful preoperative urologic evaluation, including cystometry. Postoperative bladder care should emphasize the prevention of overdistention. Inability to empty the bladder after operation may be managed effectively by intermittent self-catheterization, Urecholine, or prolonged catheter drainage. Patients should be evaluated periodically to uncover delayed bladder decompensation.", "contents": "Bladder dysfunction after radical abdominal hysterectomy. Bladder dysfunction is a common occurrence following radical hysterectomy. We studied bladder function prospectively in 10 patients before and after radical hysterectomy. Results suggest that the hypertonic phase observed immediately postoperatively is the result of an increase in myogenic tonicity of the detrusor muscle secondary to the trauma of operation and prolonged catheter drainage. The inability of patients to urinate effectively is due to partial detrusor denervation. Combined cystometry and electromyography confirmed the presence of normal sphincter function and the absence of detrusor sphincter dyssynergia. Prevention of postoperative bladder atony includes a careful preoperative urologic evaluation, including cystometry. Postoperative bladder care should emphasize the prevention of overdistention. Inability to empty the bladder after operation may be managed effectively by intermittent self-catheterization, Urecholine, or prolonged catheter drainage. Patients should be evaluated periodically to uncover delayed bladder decompensation."}
{"id": "PMID:18010", "title": "Effects of prolonged infusion of beta-adrenergic agonists on uterine and umbilical blood flow in pregnant sheep.", "content": "We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol.", "contents": "Effects of prolonged infusion of beta-adrenergic agonists on uterine and umbilical blood flow in pregnant sheep. We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol."}
{"id": "PMID:18011", "title": "Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia.", "content": "Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered.", "contents": "Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia. Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered."}
{"id": "PMID:18013", "title": "Thyroid cold acclimation influences on norepinephrine metabolism in brown fat.", "content": "Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect.", "contents": "Thyroid cold acclimation influences on norepinephrine metabolism in brown fat. Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect."}
{"id": "PMID:18014", "title": "Hexose monophosphate shunt in isolated cardiac myocytes from normal rats.", "content": "The activity of the hexose monophosphate shunt was studied in myocytes obtained from the ventricles of normal, adult, male rats. When myocytes were incubated in buffer containing either 1-14C- or 6-14C-labeled glucose the ratio of C-1/C-6 14CO2 evolved was essentially unity. The addition of plasma levels of amino acids did not alter this finding. If, however, a competitive substrate (pyruvate, octanoate, acetate, or lactate) was present, in sufficient quantity to lower the oxidation of glucose to approximately 20% of the control, the C-1/C-6 14CO2 ratio rose to values between 1.3 and 2.1. This ratio was dependent on the concentration of the competitive substrate, which was dependent on the buffer system. The data indicates that the hexose monophosphate shunt is active in the heart because it can be demonstrated when a substrate, which competes with glucose for oxidation, is present. The presence of competing substrates parallels the situation occuring in vivo.", "contents": "Hexose monophosphate shunt in isolated cardiac myocytes from normal rats. The activity of the hexose monophosphate shunt was studied in myocytes obtained from the ventricles of normal, adult, male rats. When myocytes were incubated in buffer containing either 1-14C- or 6-14C-labeled glucose the ratio of C-1/C-6 14CO2 evolved was essentially unity. The addition of plasma levels of amino acids did not alter this finding. If, however, a competitive substrate (pyruvate, octanoate, acetate, or lactate) was present, in sufficient quantity to lower the oxidation of glucose to approximately 20% of the control, the C-1/C-6 14CO2 ratio rose to values between 1.3 and 2.1. This ratio was dependent on the concentration of the competitive substrate, which was dependent on the buffer system. The data indicates that the hexose monophosphate shunt is active in the heart because it can be demonstrated when a substrate, which competes with glucose for oxidation, is present. The presence of competing substrates parallels the situation occuring in vivo."}
{"id": "PMID:18015", "title": "HCO3- and H+ secretion in rat ileum in vivo.", "content": "Replacing Cl- in the perfusion fluids decreased the luminal pH of rat ileum perfused in vivo. Varying the initial pH in Cl- depletion studies indicated an equilibrium pH near 6.6. Na+ depletion in Cl- deleted fluids partially inhibited luminal acidification. Addition of HCO3- accelerated Na+ absorption and decreased Cl- absorption. Luminal PCO2 was increased using fluids buffered to initial pH 6.6, suggesting secretion of HCO3- rather than OH-. The decreased HCO3- secretion using Cl- depleted fluids was not due to an acclerated rate of H+ secretion. Reaffirmed and expanded in this study is an ileal H+ secretory process that is partially related to Na+ absorption and direct HCO3- secretion that is related to Cl- and Na+ absorption.", "contents": "HCO3- and H+ secretion in rat ileum in vivo. Replacing Cl- in the perfusion fluids decreased the luminal pH of rat ileum perfused in vivo. Varying the initial pH in Cl- depletion studies indicated an equilibrium pH near 6.6. Na+ depletion in Cl- deleted fluids partially inhibited luminal acidification. Addition of HCO3- accelerated Na+ absorption and decreased Cl- absorption. Luminal PCO2 was increased using fluids buffered to initial pH 6.6, suggesting secretion of HCO3- rather than OH-. The decreased HCO3- secretion using Cl- depleted fluids was not due to an acclerated rate of H+ secretion. Reaffirmed and expanded in this study is an ileal H+ secretory process that is partially related to Na+ absorption and direct HCO3- secretion that is related to Cl- and Na+ absorption."}
{"id": "PMID:18016", "title": "Neural control of glycogen content and its diurnal rhythm in mouse pineal cell.", "content": "In adult male dd mice, possible mechanisms regulating the glycogen content in the pineal cell were investigated by a semiquantitative histochemical method, with particular reference to the role of the sympathetic innervation. Reserpine, superior cervical ganglionectomy (SCGX), or decentralization of the ganglia (DC), as well as continuous light, prevented the nocturnal decrease in the glycogen content, causing a marked increase, and caused a gradual decrease in the size of the pineal cell. In the SCGX or DC group, the glycogen content reached a peak at 2 days and then decreased gradually. The nocturnal decrease was also prevented by propranolol. Noradrenaline caused a marked decrease in the glycogen content. These findings support the hypothesis that the glycogen metabolism and its diurnal rhythm in the pineal cell are regulated by the sympathetic nerve terminals innervating the pineal gland, presumably by the release of noradrenaline. In addition, the nature of the internal mechanism in the organism generating the pineal glycogen rhythm was examined. Light was considered to induce a phase shift in such a mechanism, but reserpine was not.", "contents": "Neural control of glycogen content and its diurnal rhythm in mouse pineal cell. In adult male dd mice, possible mechanisms regulating the glycogen content in the pineal cell were investigated by a semiquantitative histochemical method, with particular reference to the role of the sympathetic innervation. Reserpine, superior cervical ganglionectomy (SCGX), or decentralization of the ganglia (DC), as well as continuous light, prevented the nocturnal decrease in the glycogen content, causing a marked increase, and caused a gradual decrease in the size of the pineal cell. In the SCGX or DC group, the glycogen content reached a peak at 2 days and then decreased gradually. The nocturnal decrease was also prevented by propranolol. Noradrenaline caused a marked decrease in the glycogen content. These findings support the hypothesis that the glycogen metabolism and its diurnal rhythm in the pineal cell are regulated by the sympathetic nerve terminals innervating the pineal gland, presumably by the release of noradrenaline. In addition, the nature of the internal mechanism in the organism generating the pineal glycogen rhythm was examined. Light was considered to induce a phase shift in such a mechanism, but reserpine was not."}
{"id": "PMID:18017", "title": "Function of human platelets during extracorporeal circulation.", "content": "The interaction between human platelets and nonbiologic surfaces was studied during in vitro recirculation of 500 ml of fresh, heparinized human blood in four different perfusion circuits. Circuits differed in surface area (0.1 m2 or 0.9 m2) and in surface composition. No important differences were observed between standard silicone-rubber and filler-free, silicone-rubber surfaces. Platelet counts decreased to 85% of control in 0.1- m2 circuits, but retained normal sensitivity to aggregating agents and released only small amounts of platelet factor 4 (PF4). In contrast, platelet counts in 0.9-m2 circuits decreased to 20% of control within 2 min and platelet sensitivity was depressed out of proportion to the fall in platelet count. Plasma PF4 progressively increased and platelet PF4 content progressively decreased during 6 h of recirculation. The results indicate that human platelets may exist in three conditions during extracorporeal circulation. Some platelets are unaltered, some are less sensitive to aggregating agents, and others have undergone extensive release. The ratio of blood volume to surface area appears to be an important determinant of platelet-surface interaction.", "contents": "Function of human platelets during extracorporeal circulation. The interaction between human platelets and nonbiologic surfaces was studied during in vitro recirculation of 500 ml of fresh, heparinized human blood in four different perfusion circuits. Circuits differed in surface area (0.1 m2 or 0.9 m2) and in surface composition. No important differences were observed between standard silicone-rubber and filler-free, silicone-rubber surfaces. Platelet counts decreased to 85% of control in 0.1- m2 circuits, but retained normal sensitivity to aggregating agents and released only small amounts of platelet factor 4 (PF4). In contrast, platelet counts in 0.9-m2 circuits decreased to 20% of control within 2 min and platelet sensitivity was depressed out of proportion to the fall in platelet count. Plasma PF4 progressively increased and platelet PF4 content progressively decreased during 6 h of recirculation. The results indicate that human platelets may exist in three conditions during extracorporeal circulation. Some platelets are unaltered, some are less sensitive to aggregating agents, and others have undergone extensive release. The ratio of blood volume to surface area appears to be an important determinant of platelet-surface interaction."}
{"id": "PMID:18018", "title": "Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade.", "content": "Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy.", "contents": "Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade. Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy."}
{"id": "PMID:18019", "title": "Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats.", "content": "The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction.", "contents": "Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats. The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction."}
{"id": "PMID:18020", "title": "Active alkalinization by amphibian gastric fundic mucosa in vitro.", "content": "Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55  microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents.", "contents": "Active alkalinization by amphibian gastric fundic mucosa in vitro. Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55  microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents."}
{"id": "PMID:18021", "title": "Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH.", "content": "The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli.", "contents": "Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH. The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli."}
{"id": "PMID:18022", "title": "Influence of aldosterone on renal ammonia production.", "content": "Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis.", "contents": "Influence of aldosterone on renal ammonia production. Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis."}
{"id": "PMID:18023", "title": "Solute permeability of the alveolar epithelium in acute hemodynamic pulmonary edema in dogs.", "content": "Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema.", "contents": "Solute permeability of the alveolar epithelium in acute hemodynamic pulmonary edema in dogs. Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema."}
{"id": "PMID:18024", "title": "Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats.", "content": "Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate.", "contents": "Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats. Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate."}
{"id": "PMID:18025", "title": "Properties of the laryngeal chemoreflex in neonatal piglets.", "content": "Cardiorespiratory reflex responses to laryngeal chemoreceptor stimulation were studied in 62 piglets of both sexes varying in age from 1 to 79 days. The distal trachea was cannulated to provide a free airway and the proximal end used to introduce fluids into the laryngeal area. Introduction of either water or milk produced apnea, bradycardia, and hypertension. Swab application of test fluids to the laryngeal epithelium produced similar responses. The reflex could be interrupted by flushing the laryngeal region with saline, by cutting the superior laryngeal nerves (SLN) or by anesthetizing the laryngeal epithelium with lidocaine. Electrical stimulation of SLN elicited identical responses. Respiratory inhibition by the reflex was enhanced following central depression with chloralose and overridden by administration of the respiratory stimulant, aminophylline. The relative potency of the laryngeal reflex was estimated to be equivalent to about 40% of the dose of chloralose which produced permanent respiratory arrest. It is concluded that in circumstances where respiratory drive is reduced the laryngeal inhibitory reflex is capable of caused persistent apnea and asphyxial death in the young piglet.", "contents": "Properties of the laryngeal chemoreflex in neonatal piglets. Cardiorespiratory reflex responses to laryngeal chemoreceptor stimulation were studied in 62 piglets of both sexes varying in age from 1 to 79 days. The distal trachea was cannulated to provide a free airway and the proximal end used to introduce fluids into the laryngeal area. Introduction of either water or milk produced apnea, bradycardia, and hypertension. Swab application of test fluids to the laryngeal epithelium produced similar responses. The reflex could be interrupted by flushing the laryngeal region with saline, by cutting the superior laryngeal nerves (SLN) or by anesthetizing the laryngeal epithelium with lidocaine. Electrical stimulation of SLN elicited identical responses. Respiratory inhibition by the reflex was enhanced following central depression with chloralose and overridden by administration of the respiratory stimulant, aminophylline. The relative potency of the laryngeal reflex was estimated to be equivalent to about 40% of the dose of chloralose which produced permanent respiratory arrest. It is concluded that in circumstances where respiratory drive is reduced the laryngeal inhibitory reflex is capable of caused persistent apnea and asphyxial death in the young piglet."}
{"id": "PMID:18027", "title": "[The aging alimentary tract (author's transl)].", "content": "The physiological process of aging causes changes in volumen and composition of saliva, gastric and pancreatic juice and bile flow, a diminished absorption and an altered bacterial flora. However, these changes are compensated and do not cause symptoms. Besides of an increased disposition to develop carcinoma of the gut the alimentary tract in contrast to the cardiovascular system has no specific symptomatology as signs of wear. In old age, too, functional disorders rank first in clinical symptomatology.", "contents": "[The aging alimentary tract (author's transl)]. The physiological process of aging causes changes in volumen and composition of saliva, gastric and pancreatic juice and bile flow, a diminished absorption and an altered bacterial flora. However, these changes are compensated and do not cause symptoms. Besides of an increased disposition to develop carcinoma of the gut the alimentary tract in contrast to the cardiovascular system has no specific symptomatology as signs of wear. In old age, too, functional disorders rank first in clinical symptomatology."}
{"id": "PMID:18028", "title": "[Differentiation of the aging intestinal epithelium by morphology, histochemistry and discelectrophoresis (author's transl)].", "content": "The intestinal epithelium of the small and large intestine of fetal rats (19th, 20th and 21st day of pregnancy) newborn and juvenile rats (1st to 50th day of life) adult rats (3rd to 4th month) and senile rats (18th to 30th month) was investigated by means of morphology, enzyme histochemistry and discelectrophoresis. The results obtained permit division of the development and aging of the rat intestinal epithelium into five periods: 1. The period of prenatal development. 2. The period of postnatal development. 3. The period of adaptation. 4. The stage of adult maturity. 5. The senile atrophy of the intestinal mucosa.", "contents": "[Differentiation of the aging intestinal epithelium by morphology, histochemistry and discelectrophoresis (author's transl)]. The intestinal epithelium of the small and large intestine of fetal rats (19th, 20th and 21st day of pregnancy) newborn and juvenile rats (1st to 50th day of life) adult rats (3rd to 4th month) and senile rats (18th to 30th month) was investigated by means of morphology, enzyme histochemistry and discelectrophoresis. The results obtained permit division of the development and aging of the rat intestinal epithelium into five periods: 1. The period of prenatal development. 2. The period of postnatal development. 3. The period of adaptation. 4. The stage of adult maturity. 5. The senile atrophy of the intestinal mucosa."}
{"id": "PMID:18029", "title": "[Gastroscopic findings in aged patients (author's transl)].", "content": "Endoscopic findings in a group of 169 aged patients are shown to be concentrated in the stomach, whereas pathologic findings in the duodenal bulb are less frequent. In comparison to a group of young patients gastric mucosal atrophy, gastric ulcer, carcinoma of the operated and unoperated stomach, polyps are predominant in the aged patients. Approximately one half of carcinomas were seen in patients operated by the Billroth II technique. On behalf of this fact it is necessary to review patients endoscopically from the fifteenth year after operation on with regularity in order to detect growth of carcinoma in the early stage.", "contents": "[Gastroscopic findings in aged patients (author's transl)]. Endoscopic findings in a group of 169 aged patients are shown to be concentrated in the stomach, whereas pathologic findings in the duodenal bulb are less frequent. In comparison to a group of young patients gastric mucosal atrophy, gastric ulcer, carcinoma of the operated and unoperated stomach, polyps are predominant in the aged patients. Approximately one half of carcinomas were seen in patients operated by the Billroth II technique. On behalf of this fact it is necessary to review patients endoscopically from the fifteenth year after operation on with regularity in order to detect growth of carcinoma in the early stage."}
{"id": "PMID:18030", "title": "[Gastroduodenal ulcers in patients of a geriatric hospital (author's transl)].", "content": "Among 3646 patients of a geriatric hospital we we found 7,82% = 285 patients who suffered once in their life from a gastroduodenal ulcer. We noted: 1. gastroduodenal scars in 3,3% = 121 cases, 2. anamnestic proved gastroduodenal ulcer disease in 1,5% = 57 cases, 3. clinical and/or pathological proved gastroduodenal ulcers in 3% = 107 cases. Additional findings were put down as there are aortal arteriosclerosis, pulmonary heart and complications like perforation, penetration, bleeding and death.", "contents": "[Gastroduodenal ulcers in patients of a geriatric hospital (author's transl)]. Among 3646 patients of a geriatric hospital we we found 7,82% = 285 patients who suffered once in their life from a gastroduodenal ulcer. We noted: 1. gastroduodenal scars in 3,3% = 121 cases, 2. anamnestic proved gastroduodenal ulcer disease in 1,5% = 57 cases, 3. clinical and/or pathological proved gastroduodenal ulcers in 3% = 107 cases. Additional findings were put down as there are aortal arteriosclerosis, pulmonary heart and complications like perforation, penetration, bleeding and death."}
{"id": "PMID:18031", "title": "[Ischemic bowel disease (author's transl)].", "content": "Geriatric patients are preferentially involved in ischemic bowel disease. The sudden occlusion of the large mesenteric arteries (a. mesenterica superior (more frequently) and inferior) is followed by intestinal gangrene and peritonitis with a poor prognosis and a high letality (greater than 90%). In chronic intestinal ischemia the leading clinical symptom is postprandial pain ('claudicatio intestinalis'). In some cases of acute mesenteric artery occlusion no embolus or thrombus will be found. In these cases the circulation in the arteriosclerotic vessels falls below a critical value due to cardiac insufficiency, shock, digitalis overdose and others. In less severe ischemia the mucosa is involved being most sensitive to O2 deprivation. It usually regenerates within a few days. This form is found more frequently in the colon than in other parts of the gut (about 40%): ischemic colitis. The therapy - if possible in acute, fulminant ischemia or if necessary in chronic intestinal ischemia - is surgical consisting in reconstructive procedures of the mesenteric circulation.", "contents": "[Ischemic bowel disease (author's transl)]. Geriatric patients are preferentially involved in ischemic bowel disease. The sudden occlusion of the large mesenteric arteries (a. mesenterica superior (more frequently) and inferior) is followed by intestinal gangrene and peritonitis with a poor prognosis and a high letality (greater than 90%). In chronic intestinal ischemia the leading clinical symptom is postprandial pain ('claudicatio intestinalis'). In some cases of acute mesenteric artery occlusion no embolus or thrombus will be found. In these cases the circulation in the arteriosclerotic vessels falls below a critical value due to cardiac insufficiency, shock, digitalis overdose and others. In less severe ischemia the mucosa is involved being most sensitive to O2 deprivation. It usually regenerates within a few days. This form is found more frequently in the colon than in other parts of the gut (about 40%): ischemic colitis. The therapy - if possible in acute, fulminant ischemia or if necessary in chronic intestinal ischemia - is surgical consisting in reconstructive procedures of the mesenteric circulation."}
{"id": "PMID:18032", "title": "[Dependence of diverticulosis on age (author's transl)].", "content": "The diverticulosis of the gastrointestinal tract is a widespread senile disease. The dependence of the diverticulosis on age is investigated on the basis of 1 000 proven cases of this disease. The importance of the anatomicomorphological lesions of the organs at old age as its cause is pointed out. The males seem to be affected by the diverticulosis somewhat more than the females, whereas its percental manifestation in the different organs is about equal for both sexes. It prevails in the colon with 48.4% and in the duodenum with 35.4% of all cases of organ diverticulosis. The existence of constitutional associations with other diseases, such as diabetes mellitus, is discussed. Finally, the therapeutic problems of the diverticulitis and their dependence on age are examined.", "contents": "[Dependence of diverticulosis on age (author's transl)]. The diverticulosis of the gastrointestinal tract is a widespread senile disease. The dependence of the diverticulosis on age is investigated on the basis of 1 000 proven cases of this disease. The importance of the anatomicomorphological lesions of the organs at old age as its cause is pointed out. The males seem to be affected by the diverticulosis somewhat more than the females, whereas its percental manifestation in the different organs is about equal for both sexes. It prevails in the colon with 48.4% and in the duodenum with 35.4% of all cases of organ diverticulosis. The existence of constitutional associations with other diseases, such as diabetes mellitus, is discussed. Finally, the therapeutic problems of the diverticulitis and their dependence on age are examined."}
{"id": "PMID:18033", "title": "[Functional digestive troubles in old age (author's transl)].", "content": "Functional disorders are frequent in elderly patients. However the high incidence of organic lesions in advanced age demands a most careful examination. Each diagnosis of functional disorders made by exclusion of organic lesions has to be revised, if symptoms persist or symptomatic treatment remains inefficient. Gastroenterological diagnostic should not be restricted to an endoscopic or radiologic glance to the gastrointestinal tract. It includes the less spectacular but more human trial to get an insight to the soul of the patient. This may be more helpful than any treatment with the newest double blind tested medication.", "contents": "[Functional digestive troubles in old age (author's transl)]. Functional disorders are frequent in elderly patients. However the high incidence of organic lesions in advanced age demands a most careful examination. Each diagnosis of functional disorders made by exclusion of organic lesions has to be revised, if symptoms persist or symptomatic treatment remains inefficient. Gastroenterological diagnostic should not be restricted to an endoscopic or radiologic glance to the gastrointestinal tract. It includes the less spectacular but more human trial to get an insight to the soul of the patient. This may be more helpful than any treatment with the newest double blind tested medication."}
{"id": "PMID:18035", "title": "Age-dependent alterations of the rate of RNA synthesis in rat brain cell nuclei.", "content": "Endogenous Mn2+ and Mg2+ activated RNA polymerase activity was measured in isolated cell nuclei of brain from rats of different age-groups. It was established that the activity of the nucleoplasmic RNA polymerase is maintained at the level of young animals up to an age of 16 months but is decreased after 24 months. The nucleolar RNA polymerase activity decreases already at 16 months and a higher ratio of the Mn2+:Mg2+ activated RNA polymerase activities has been found to be characteristic for the older animals. By means of stepwise sucrose density gradient centrifugation fractions were obtained from the nuclear preparations highly enriched in cell nuclei of neuronal and glial origin respectively. By measuring the activity of the nucleoplasmic and nucleolar RNA polymerases in these fractions it was found that the elevated ratio of the nucleoplasmic to nucleolar RNA polymerase activity at 16 months of age is a characteristic of the neuronal nuclei while the glial nuclei behave by the opposite manner. A parallelism existing between the age-dependent change of the endogenous RNA polymerase activity and that of perichromatic granules of rat brain cortical cells is discussed.", "contents": "Age-dependent alterations of the rate of RNA synthesis in rat brain cell nuclei. Endogenous Mn2+ and Mg2+ activated RNA polymerase activity was measured in isolated cell nuclei of brain from rats of different age-groups. It was established that the activity of the nucleoplasmic RNA polymerase is maintained at the level of young animals up to an age of 16 months but is decreased after 24 months. The nucleolar RNA polymerase activity decreases already at 16 months and a higher ratio of the Mn2+:Mg2+ activated RNA polymerase activities has been found to be characteristic for the older animals. By means of stepwise sucrose density gradient centrifugation fractions were obtained from the nuclear preparations highly enriched in cell nuclei of neuronal and glial origin respectively. By measuring the activity of the nucleoplasmic and nucleolar RNA polymerases in these fractions it was found that the elevated ratio of the nucleoplasmic to nucleolar RNA polymerase activity at 16 months of age is a characteristic of the neuronal nuclei while the glial nuclei behave by the opposite manner. A parallelism existing between the age-dependent change of the endogenous RNA polymerase activity and that of perichromatic granules of rat brain cortical cells is discussed."}
{"id": "PMID:18034", "title": "[Nutritional problems in old age (author's transl)].", "content": "While age is increasing involutiones specific to age can be proofed at the gastrointestinal tract, which lead to a deceleration but quantitative unchanged adsorption. Wrong nutrition concerning to the take up of fat, carbohydrates, proteins and trace elements can be found in greater age very often.  By watching a collective of healthy persons beyond the age of 90 years however it turns out that this group keeps a nearly faultless nutrition. The requirements of lysin, methionin and calcium is a little higher in old age than in younger. By intermitting starvation or addition of antioxidants life can be prolonged in experiments on animals, when this therapy starts already in younger age. Starvation in higher age, however, leads to a shortening of life in experiments on animals.", "contents": "[Nutritional problems in old age (author's transl)]. While age is increasing involutiones specific to age can be proofed at the gastrointestinal tract, which lead to a deceleration but quantitative unchanged adsorption. Wrong nutrition concerning to the take up of fat, carbohydrates, proteins and trace elements can be found in greater age very often.  By watching a collective of healthy persons beyond the age of 90 years however it turns out that this group keeps a nearly faultless nutrition. The requirements of lysin, methionin and calcium is a little higher in old age than in younger. By intermitting starvation or addition of antioxidants life can be prolonged in experiments on animals, when this therapy starts already in younger age. Starvation in higher age, however, leads to a shortening of life in experiments on animals."}
{"id": "PMID:18036", "title": "[In vitro-phosphorylation of histones in chromatin of various tissues in relation to age (author's transl)].", "content": "The influence of age on the structure of chromatin of various mammalian cells with modest or terminated mitotic activity has been examined. For this purpose chromatin from dog skeletal muscle, and human neuronal and glial cells, has been incubated together with an exogenous histone phosphokinase and ATP-gamma32P, and the phosphate incorporated into the histones determined. For comparison, also free histone has been phosphorylated. The amount of phosphate incorporated into total histone is 16-18 nmol Pi per mg histone in the case of free histone, and about equal for all cell types and ages. Into chromatin-bound histones only 5.5-8.2 nmol Pi per mg histone are incorporated. The differences between the various cell types and age groups are not significant. The relative phosphate incorporation into the single histone fractions depends on the histone as being free or chromatin-bound. In addition, relative phosphate incorporation into the single fractions of chromatin-bound histones is also cell type- and age-specific. The results permit the conclusion that the chromatin is subject to structural changes in the course of aging.", "contents": "[In vitro-phosphorylation of histones in chromatin of various tissues in relation to age (author's transl)]. The influence of age on the structure of chromatin of various mammalian cells with modest or terminated mitotic activity has been examined. For this purpose chromatin from dog skeletal muscle, and human neuronal and glial cells, has been incubated together with an exogenous histone phosphokinase and ATP-gamma32P, and the phosphate incorporated into the histones determined. For comparison, also free histone has been phosphorylated. The amount of phosphate incorporated into total histone is 16-18 nmol Pi per mg histone in the case of free histone, and about equal for all cell types and ages. Into chromatin-bound histones only 5.5-8.2 nmol Pi per mg histone are incorporated. The differences between the various cell types and age groups are not significant. The relative phosphate incorporation into the single histone fractions depends on the histone as being free or chromatin-bound. In addition, relative phosphate incorporation into the single fractions of chromatin-bound histones is also cell type- and age-specific. The results permit the conclusion that the chromatin is subject to structural changes in the course of aging."}
{"id": "PMID:18037", "title": "[RNA metabolism and ageing (author's transl)].", "content": "The labelling behaviour of RNA fractions in rat liver after application of 32P-orthophosphate and 14C-orotate in vivo in young (3-5 months) and old animals (20 months) was presented. Whereas the tracer incorporation in old animals 60 minutes after 32P-application seems to be decreased we observed increased specific activities of nuclear RNA 30 and 60 minutes after application of 14C-orotate i.p. - Measuring of RNA synthesis in isolated cell nuclei after in vivo stimulation by cortisol (2 mg/100 g body weight) showed a stronger and longer continued stimulation in young animals as in old both in the Mn++ system and in the Mg++ system. When we compared the young with the old controls the rate of synthesis was increased in the old controls. The results support observations on changed regulations of the transcription of genetic informations in the age.", "contents": "[RNA metabolism and ageing (author's transl)]. The labelling behaviour of RNA fractions in rat liver after application of 32P-orthophosphate and 14C-orotate in vivo in young (3-5 months) and old animals (20 months) was presented. Whereas the tracer incorporation in old animals 60 minutes after 32P-application seems to be decreased we observed increased specific activities of nuclear RNA 30 and 60 minutes after application of 14C-orotate i.p. - Measuring of RNA synthesis in isolated cell nuclei after in vivo stimulation by cortisol (2 mg/100 g body weight) showed a stronger and longer continued stimulation in young animals as in old both in the Mn++ system and in the Mg++ system. When we compared the young with the old controls the rate of synthesis was increased in the old controls. The results support observations on changed regulations of the transcription of genetic informations in the age."}
{"id": "PMID:18038", "title": "[The vascularisation of the granulation tissue in different ages. - Its importance for wound healing (author's transl)].", "content": "The part of capillaries of a plastic sponge granuloma was determined in rats of different ages. It was found that granulation tissue of older rats contains significantly fewer capillaries than that of young animals. The diminished vascularisation of granulation tissue may be responsible for the deterioration of wound healing in aged individuals.", "contents": "[The vascularisation of the granulation tissue in different ages. - Its importance for wound healing (author's transl)]. The part of capillaries of a plastic sponge granuloma was determined in rats of different ages. It was found that granulation tissue of older rats contains significantly fewer capillaries than that of young animals. The diminished vascularisation of granulation tissue may be responsible for the deterioration of wound healing in aged individuals."}
{"id": "PMID:18039", "title": "[Histone phosphorylation of human lymphocytes after PHA stimulation in relation to age (author's transl)].", "content": "Lymphocytes of young and old donors are stimulated by phytohemagglutinin (PHA). The 32P-incorporation into the histones which occurs in the early phase after PHA-stimulation is determined. In lymphocytes of old persons the 32P-incorporation in the histones is diminished by about 50% with respect to the cells of young donors. Furthermore, it could be shown that in the histones prepared from old cells the amount of H1 is much increased. It is postulated that, in old age, the other 4 histones are poorly extractable.", "contents": "[Histone phosphorylation of human lymphocytes after PHA stimulation in relation to age (author's transl)]. Lymphocytes of young and old donors are stimulated by phytohemagglutinin (PHA). The 32P-incorporation into the histones which occurs in the early phase after PHA-stimulation is determined. In lymphocytes of old persons the 32P-incorporation in the histones is diminished by about 50% with respect to the cells of young donors. Furthermore, it could be shown that in the histones prepared from old cells the amount of H1 is much increased. It is postulated that, in old age, the other 4 histones are poorly extractable."}
{"id": "PMID:18040", "title": "[Hydroxylation of skin collagen in relation to age: analyses of the human skin].", "content": "The results of human skin analysis are demonstrated. It has been pointed out, that the content of hydroxyproline and hydroxylysine, in addition to the usual variation as the other aminoacids varies extensively. The extent of hydroxylation was estimated from the relation of OH-aminoacids to (not hydroxylated) each other. The determined variation of the results is most probably due to a different collagen hydroxylation within the biological dispersion. An age-related degree of hydroxylation could not be detected.", "contents": "[Hydroxylation of skin collagen in relation to age: analyses of the human skin]. The results of human skin analysis are demonstrated. It has been pointed out, that the content of hydroxyproline and hydroxylysine, in addition to the usual variation as the other aminoacids varies extensively. The extent of hydroxylation was estimated from the relation of OH-aminoacids to (not hydroxylated) each other. The determined variation of the results is most probably due to a different collagen hydroxylation within the biological dispersion. An age-related degree of hydroxylation could not be detected."}
{"id": "PMID:18041", "title": "[Investigations about the effect of run-training and run-stress on glucose tolerance and insulin secretion with ageing streptozotocin-diabetic rats (author's transl)].", "content": "Untrained grown-up and old rats with a mild Streptozotocin-diabetes show in i.v. glucose tolerance test a pathological glucose assimilation and diminished insulin secretion in comparison to control rats of the same age after a maximal run-stress. Trained rats show a different behaviour in glucose tolerance test depending on their age and seriousness of diabetes: Glucose tolerance is improved in grown-up rats with a mild diabetes and unchanged in old rats. Six-week run-training causes a significant deterioration of glucose tolerance in rats with a medium seriously Streptozotocin-diabetes and even leads to death of old rats because of decompensated metabolism. Grown-up rats with a mild diabetes stand run-stress after run-training better than the old ones. No animal with a medium seriously diabetes survives maximal run-stress, old rats don't even survive the slowly increasing run-training. - These results confirm the dualistic effect of muscular work. Metabolism of mild diabetes becomes better through muscular exertion the one of medium diabetes gets worse. Therefore a good effect of run-training is measurable only in grown-up rats not in old ones.", "contents": "[Investigations about the effect of run-training and run-stress on glucose tolerance and insulin secretion with ageing streptozotocin-diabetic rats (author's transl)]. Untrained grown-up and old rats with a mild Streptozotocin-diabetes show in i.v. glucose tolerance test a pathological glucose assimilation and diminished insulin secretion in comparison to control rats of the same age after a maximal run-stress. Trained rats show a different behaviour in glucose tolerance test depending on their age and seriousness of diabetes: Glucose tolerance is improved in grown-up rats with a mild diabetes and unchanged in old rats. Six-week run-training causes a significant deterioration of glucose tolerance in rats with a medium seriously Streptozotocin-diabetes and even leads to death of old rats because of decompensated metabolism. Grown-up rats with a mild diabetes stand run-stress after run-training better than the old ones. No animal with a medium seriously diabetes survives maximal run-stress, old rats don't even survive the slowly increasing run-training. - These results confirm the dualistic effect of muscular work. Metabolism of mild diabetes becomes better through muscular exertion the one of medium diabetes gets worse. Therefore a good effect of run-training is measurable only in grown-up rats not in old ones."}
{"id": "PMID:18042", "title": "[Determination of neurophysiological parameters of the aging CNS. I. Evoked potentials (author's transl)].", "content": "Somatosensory (SEP) and visual (VEP) evoked potentials were studied in 65 healthy subjects who ranged in age from 62-91 years and in 48 normal persons aged 18-38 years. The amplitudes and latencies of the different components of the evoked potentials were measured. The transmission of evoked potentials from the specific response area into different regions of the ipsi- and contralateral hemisphere were studied. The findings can be summarized as follows: The latencies of the SEP and VEP of aged subjects are significantly prolonged. The increase in latency is relatively slight for the first components, progressively higher for the following components. The amplitudes of the different components of the SEP and VEP are significantly increased in aged subjects. The modifications of the SEP-latencies and of the VEP-amplitudes are more important over the dominant hemisphere. In young subjects the SE are confirmed to the centro-parietal region. In aged persons the SEP spreads over the whole hemisphere. The hypothesis that the aging process involves the synaptic transmitter mechanisms at the cortical level is discussed in relation to the involvement of the latencies. The increase in amplitude of the evoked potentials could be explained by assuming that the inhibition - an essential property of the cortex - decreases during the aging process.", "contents": "[Determination of neurophysiological parameters of the aging CNS. I. Evoked potentials (author's transl)]. Somatosensory (SEP) and visual (VEP) evoked potentials were studied in 65 healthy subjects who ranged in age from 62-91 years and in 48 normal persons aged 18-38 years. The amplitudes and latencies of the different components of the evoked potentials were measured. The transmission of evoked potentials from the specific response area into different regions of the ipsi- and contralateral hemisphere were studied. The findings can be summarized as follows: The latencies of the SEP and VEP of aged subjects are significantly prolonged. The increase in latency is relatively slight for the first components, progressively higher for the following components. The amplitudes of the different components of the SEP and VEP are significantly increased in aged subjects. The modifications of the SEP-latencies and of the VEP-amplitudes are more important over the dominant hemisphere. In young subjects the SE are confirmed to the centro-parietal region. In aged persons the SEP spreads over the whole hemisphere. The hypothesis that the aging process involves the synaptic transmitter mechanisms at the cortical level is discussed in relation to the involvement of the latencies. The increase in amplitude of the evoked potentials could be explained by assuming that the inhibition - an essential property of the cortex - decreases during the aging process."}
{"id": "PMID:18065", "title": "[Lens changes occuring as a result of lowered pH (acidosis) (author's transl)].", "content": "In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out.", "contents": "[Lens changes occuring as a result of lowered pH (acidosis) (author's transl)]. In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out."}
{"id": "PMID:18069", "title": "[The present state of hypotension (author's transl)].", "content": "The study was made of the recent literature on controlled hypotension and its place in modern anaesthetic practice. The effects of the different techniques and drugs are outlined in this paper. The results of investigation revealed that the circulation of heart, brain, liver, and kidneys is able to tolerate a wide range of deviation of blood pressure. Hypotension induced by high doses of halothane alone, which used to be considered as an adequate measure, has recently been shown to cause such serious side-effects that it can no longer be recommended. Halothane lowers blood pressure almost exclusively by means of a reduction of the contractility of the heart muscle. Ganglionic blocking agents alone should not be used either because of their depressing effect on the heart; moreover their hypotensive effects are hard to control. The sole exception is trimetaphan but it produces other severe side-effects such as liberation of histamine. On the other hand ganglionic blocking agents combined with halothane can be recommended. The combined administration of these drugs allow an easy control of hypotension and the side effects are minimal. Only sodium-nitroprusside meets all the requirements of a hypotensive drug. It operates selectively in a peripheral vasoplegic manner without effecting the cerebral centres. Regarding the heart, no side-effect is known apart from tachycardia; cardiac output is not altered. The metabolism of sodium-nitroprusside requires precaution in dosage, as degradation takes place via the toxic compounds of cyanide. Therefore liver disease and disturbances in vitamin B12 utilisation are regarded as contraindications for the use of nitroprusside. That is also the reason why a maximum allowable dose of 10-15 gamma/kg body weight and minute should not be exceeded. Prophylactic administration of vitamin B 12a (hydroxocobalamin) should be considered in every case when nitroprusside is used.", "contents": "[The present state of hypotension (author's transl)]. The study was made of the recent literature on controlled hypotension and its place in modern anaesthetic practice. The effects of the different techniques and drugs are outlined in this paper. The results of investigation revealed that the circulation of heart, brain, liver, and kidneys is able to tolerate a wide range of deviation of blood pressure. Hypotension induced by high doses of halothane alone, which used to be considered as an adequate measure, has recently been shown to cause such serious side-effects that it can no longer be recommended. Halothane lowers blood pressure almost exclusively by means of a reduction of the contractility of the heart muscle. Ganglionic blocking agents alone should not be used either because of their depressing effect on the heart; moreover their hypotensive effects are hard to control. The sole exception is trimetaphan but it produces other severe side-effects such as liberation of histamine. On the other hand ganglionic blocking agents combined with halothane can be recommended. The combined administration of these drugs allow an easy control of hypotension and the side effects are minimal. Only sodium-nitroprusside meets all the requirements of a hypotensive drug. It operates selectively in a peripheral vasoplegic manner without effecting the cerebral centres. Regarding the heart, no side-effect is known apart from tachycardia; cardiac output is not altered. The metabolism of sodium-nitroprusside requires precaution in dosage, as degradation takes place via the toxic compounds of cyanide. Therefore liver disease and disturbances in vitamin B12 utilisation are regarded as contraindications for the use of nitroprusside. That is also the reason why a maximum allowable dose of 10-15 gamma/kg body weight and minute should not be exceeded. Prophylactic administration of vitamin B 12a (hydroxocobalamin) should be considered in every case when nitroprusside is used."}
{"id": "PMID:18070", "title": "[Cardiovascular effects of flunitrazepam (rohypnol, RO-5-4200) (author's transl)].", "content": "We reported on the haemodynamic effects of 0.03 mg/kg flunitrazepam during surgical procedures in neuroleptanalgesia in 39 patients with congenital or acquired heart diseases, functional class II-IV. The benzodiazepine derivative did not cause any relevant effect on the inotropic state of the myocardium. There were only minor changes in cardiac index, stroke index, right and left atrial pressure. Changes in arterial pressure and left ventricular pressure during and immediately after surgical procedures, and in arterial perfusion pressure during extracorporeal circulation, as well as an only short lasting increase in heart rate were demonstrative a peripheral vasodilator effect. The decrease in ventricular work and myocardial oxygen consumption are of value in patients with coronary heart disease, especially immediately after surgical procedures. Flunitrazepam is considered an additional drug during neuroleptanalgesia, when hypertension is causing some problems.", "contents": "[Cardiovascular effects of flunitrazepam (rohypnol, RO-5-4200) (author's transl)]. We reported on the haemodynamic effects of 0.03 mg/kg flunitrazepam during surgical procedures in neuroleptanalgesia in 39 patients with congenital or acquired heart diseases, functional class II-IV. The benzodiazepine derivative did not cause any relevant effect on the inotropic state of the myocardium. There were only minor changes in cardiac index, stroke index, right and left atrial pressure. Changes in arterial pressure and left ventricular pressure during and immediately after surgical procedures, and in arterial perfusion pressure during extracorporeal circulation, as well as an only short lasting increase in heart rate were demonstrative a peripheral vasodilator effect. The decrease in ventricular work and myocardial oxygen consumption are of value in patients with coronary heart disease, especially immediately after surgical procedures. Flunitrazepam is considered an additional drug during neuroleptanalgesia, when hypertension is causing some problems."}
{"id": "PMID:18071", "title": "Intramuscular lorazepam versus pentobarbital premedication: a comparison of patient sedation, anxiolysis, and recall.", "content": "In a double-blind, controlled study in 40 veterans, IM lorazepam was significantly superior to IM pentobarbital as a preoperative sedative and in ability to suppress the memory of events of the operative day. A trend was noted (not statistically in this small series) toward greater patient acceptance of lorazepam. No important adverse effects or changes in vital signs occurred with either agent.", "contents": "Intramuscular lorazepam versus pentobarbital premedication: a comparison of patient sedation, anxiolysis, and recall. In a double-blind, controlled study in 40 veterans, IM lorazepam was significantly superior to IM pentobarbital as a preoperative sedative and in ability to suppress the memory of events of the operative day. A trend was noted (not statistically in this small series) toward greater patient acceptance of lorazepam. No important adverse effects or changes in vital signs occurred with either agent."}
{"id": "PMID:18075", "title": "New techniques to measure blood cholinesterase activity in domesticated animals.", "content": "A macromethod and a semimicromethod were developed to measure erythrocyte acetylcholinesterase activity in cattle, sheep, goats, horses, dogs, and swine, and to measure plasma cholinesterase activity in horses, dogs, and swine. Comparison of the 2 methods with erythrocytes of sheep, cattle, goats, and horses indicated both methods gave similar results. They can be done in a shorter time and are more sensitive than Michel's method. Normal deltapH values per minutes, with standard deviations for blood cholinesterase activity of animals of different ages, sexes, breeds, and species, were: 0.76 +/- 0.12/30; 0.65 +/- 0.10/15; 0.69 +/- 0.19/45; 0.78 +/- 0.11/45; 0.63 +/- 0.11/45; and 0.71 +/- 0.06/25 for sheep, cattle, goats, horses, dogs, and swine erythrocyte acetylcholinesterase, respectively; and 0.66 +/- 0.18/20; 0.67 +/- 0.20/30, and 0.46 +/- 0.05/60 for horses, dogs, and swine plasma cholinesterase, respectively. It was shown that either the chloride or the iodide salt of acetylcholine can be used as the enzyme substrate. tin blood samples stored at 5 C for 24 hours, there was no significant change of the enzymatic activity.", "contents": "New techniques to measure blood cholinesterase activity in domesticated animals. A macromethod and a semimicromethod were developed to measure erythrocyte acetylcholinesterase activity in cattle, sheep, goats, horses, dogs, and swine, and to measure plasma cholinesterase activity in horses, dogs, and swine. Comparison of the 2 methods with erythrocytes of sheep, cattle, goats, and horses indicated both methods gave similar results. They can be done in a shorter time and are more sensitive than Michel's method. Normal deltapH values per minutes, with standard deviations for blood cholinesterase activity of animals of different ages, sexes, breeds, and species, were: 0.76 +/- 0.12/30; 0.65 +/- 0.10/15; 0.69 +/- 0.19/45; 0.78 +/- 0.11/45; 0.63 +/- 0.11/45; and 0.71 +/- 0.06/25 for sheep, cattle, goats, horses, dogs, and swine erythrocyte acetylcholinesterase, respectively; and 0.66 +/- 0.18/20; 0.67 +/- 0.20/30, and 0.46 +/- 0.05/60 for horses, dogs, and swine plasma cholinesterase, respectively. It was shown that either the chloride or the iodide salt of acetylcholine can be used as the enzyme substrate. tin blood samples stored at 5 C for 24 hours, there was no significant change of the enzymatic activity."}
{"id": "PMID:18072", "title": "Selection of the source of mixed venous blood samples in severely traumatized patients.", "content": "The technic of balloon flotation catheterization represents a significant advance in providing an additional aid to diagnosis, clinical assessment, and management of the critically ill. The fact that such patients are admitted to an intensive care unit (ICU) invariably presumes that their management will include close and accurate monitoring of the cardiovascular and respiratory systems. In a prospective study of 51 patients, not in clinical shock, in an ICU, the authors demonstrated that superior vena cava samples are not a reliable index of mixed venous blood saturation in the critically injured patient, and that a pulmonary arterial catheter is essential for obtaining true mixed venous samples for valid estimations of intrapulmonary shunts and arteriovenous O2 content differences.", "contents": "Selection of the source of mixed venous blood samples in severely traumatized patients. The technic of balloon flotation catheterization represents a significant advance in providing an additional aid to diagnosis, clinical assessment, and management of the critically ill. The fact that such patients are admitted to an intensive care unit (ICU) invariably presumes that their management will include close and accurate monitoring of the cardiovascular and respiratory systems. In a prospective study of 51 patients, not in clinical shock, in an ICU, the authors demonstrated that superior vena cava samples are not a reliable index of mixed venous blood saturation in the critically injured patient, and that a pulmonary arterial catheter is essential for obtaining true mixed venous samples for valid estimations of intrapulmonary shunts and arteriovenous O2 content differences."}
{"id": "PMID:18078", "title": "Drug therapy in the management of asthma.", "content": "In the past decade there has been substantial improvement in the quality of drug therapy for asthma. In part, this reflects the greater sophistication and confidence in the use of bronchodilator drugs, after their role in modifying the intracellular concentration of cyclic nucleotides was discovered. Another advance has come from the appearance of adequate information on theophylline blood levels and half-lives and their variability in man. The increasing availability of theophylline blood levels has aided not only in the selection of therapeutic doses but also in determining the effectiveness of newer products that, for example, promise to have a more sustained effect when given by mouth. The plight of asthmatic patients dependent on oral glucosteroid therapy has been substantially eased with the development of new steroid-sparing drugs that are effective by inhalation.", "contents": "Drug therapy in the management of asthma. In the past decade there has been substantial improvement in the quality of drug therapy for asthma. In part, this reflects the greater sophistication and confidence in the use of bronchodilator drugs, after their role in modifying the intracellular concentration of cyclic nucleotides was discovered. Another advance has come from the appearance of adequate information on theophylline blood levels and half-lives and their variability in man. The increasing availability of theophylline blood levels has aided not only in the selection of therapeutic doses but also in determining the effectiveness of newer products that, for example, promise to have a more sustained effect when given by mouth. The plight of asthmatic patients dependent on oral glucosteroid therapy has been substantially eased with the development of new steroid-sparing drugs that are effective by inhalation."}
{"id": "PMID:18079", "title": "[Behavior therapy in disorders of dietary behavior].", "content": "Behaviour therapies using conditioning principles have been successful in the treatment of some psychopatological eating behaviours. Such have been the cases for anorexia nervosae in adolescents and adults, refusal to eat in the young child and difficulties of swallowing. Some of these cases are described. Research has been done in different countries on the applications of these methods to the treatment of obesity caused by overeating which appears very frequently in our societies. Systematic and covert desensitization and operant conditioning using positive reinforcements are more frequently used in these behaviour modification procedures than aversive methods. More recently, researches on self-control (self-reward and self-punishment) have shown it as a very efficient tool for inducing weight loss. These methods using self-control have been applied to large populations: after a first, careful examination of the patient's eating behaviour, the program of reinforcement is established. It can be partially controlled by written instructions and letters. Results are already encouraging although they need to be followed up. But more research should be done on overeating behaviours, the way they appear and are maintained and on different programs of reinforcement for weight loss.", "contents": "[Behavior therapy in disorders of dietary behavior]. Behaviour therapies using conditioning principles have been successful in the treatment of some psychopatological eating behaviours. Such have been the cases for anorexia nervosae in adolescents and adults, refusal to eat in the young child and difficulties of swallowing. Some of these cases are described. Research has been done in different countries on the applications of these methods to the treatment of obesity caused by overeating which appears very frequently in our societies. Systematic and covert desensitization and operant conditioning using positive reinforcements are more frequently used in these behaviour modification procedures than aversive methods. More recently, researches on self-control (self-reward and self-punishment) have shown it as a very efficient tool for inducing weight loss. These methods using self-control have been applied to large populations: after a first, careful examination of the patient's eating behaviour, the program of reinforcement is established. It can be partially controlled by written instructions and letters. Results are already encouraging although they need to be followed up. But more research should be done on overeating behaviours, the way they appear and are maintained and on different programs of reinforcement for weight loss."}
{"id": "PMID:18081", "title": "Isoelectric focusing of hog cholera virus.", "content": "The isoelectric point of Hog Cholera virus (Alfort strain) has been determined (pHi = 4.8). A clear stimulation of its infectivity can be recorded at this pH. The isoelectrophoretic profiles of strains isolated in the field show no significant differences.", "contents": "Isoelectric focusing of hog cholera virus. The isoelectric point of Hog Cholera virus (Alfort strain) has been determined (pHi = 4.8). A clear stimulation of its infectivity can be recorded at this pH. The isoelectrophoretic profiles of strains isolated in the field show no significant differences."}
{"id": "PMID:18082", "title": "[Spectrophotometric determination of rifampicin S in the presence of rifampicin O].", "content": "The limits of the use of the methods of direct photometric and differential spectrophotometric determination of rifamycin S containing rifamycin O as an admixture were discussed. The method of direct photometry did not provide determination of rifamycin S in the presence of rifamycin O since instability of the latter under the analysis conditions. A possibility of using the differential-spectrophotometric method for determination of rifamycin S in the presence of not more than 5 per cent of rifamycin O was shown.", "contents": "[Spectrophotometric determination of rifampicin S in the presence of rifampicin O]. The limits of the use of the methods of direct photometric and differential spectrophotometric determination of rifamycin S containing rifamycin O as an admixture were discussed. The method of direct photometry did not provide determination of rifamycin S in the presence of rifamycin O since instability of the latter under the analysis conditions. A possibility of using the differential-spectrophotometric method for determination of rifamycin S in the presence of not more than 5 per cent of rifamycin O was shown."}
{"id": "PMID:18083", "title": "Azlocillin: in vitro studies of a new semisynthetic penicillin.", "content": "The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 mug or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 mug or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli.", "contents": "Azlocillin: in vitro studies of a new semisynthetic penicillin. The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of Pseudomonas aeruginosa were inhibited at a concentration of 12.5 mug or less per ml. Azlocillin is also active against indole-negative and -positive Proteus spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 mug or less per ml. Isolates of Klebsiella spp. and Enterobacter spp. showed less susceptibility than isolates of Escherichia coli and Serratia spp. Gram-positive cocci except penicillin G-resistant Staphylococcus aureus were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of P. aeruginosa. It was not as active as mezlocillin against the majority of the other gram-negative bacilli."}
{"id": "PMID:18084", "title": "Phosphate inhibition of secondary metabolism in Serratia marcescens.", "content": "The synthesis of prodigiosin by non-proliferating cells of Serratia marcescens was examined in the presence of a wide range of concentrations of inorganic phosphate (Pi). A high elevation of pigment formation was obtained at less than or equal to 0.3 mM, and a broader but much lower elevation was obtained at 10 to 250 mM Pi. The synthesis of two immediate precursors of the pitment also was inhibited by Pi. The mechanism of action of Pi did not involve changes in pH or accumulation of the trace metal nutrient iron or zinc. Inhibition was most pronounced when Pi was added to the induction system before the onset of pigment formation. The inhibitor also diminished the burst of alkaline phosphatase activity that occurred in the period between the start of induction and appearance of prodigiosin.", "contents": "Phosphate inhibition of secondary metabolism in Serratia marcescens. The synthesis of prodigiosin by non-proliferating cells of Serratia marcescens was examined in the presence of a wide range of concentrations of inorganic phosphate (Pi). A high elevation of pigment formation was obtained at less than or equal to 0.3 mM, and a broader but much lower elevation was obtained at 10 to 250 mM Pi. The synthesis of two immediate precursors of the pitment also was inhibited by Pi. The mechanism of action of Pi did not involve changes in pH or accumulation of the trace metal nutrient iron or zinc. Inhibition was most pronounced when Pi was added to the induction system before the onset of pigment formation. The inhibitor also diminished the burst of alkaline phosphatase activity that occurred in the period between the start of induction and appearance of prodigiosin."}
{"id": "PMID:18085", "title": "Effect of cadmium on fungi and on interactions between fungi and bacteria in soil: influence of clay minerals and pH.", "content": "Fungi (Rhizopus stolonifer, Trichoderma viride, Fusarium oxysporum f. sp. conglutinans, Cunninghamella echinulata, and several species of Aspergillus and Penicillium) tolerated higher concentrations of cadmium (Cd) when grown in soil than when grown on laboratory media, indicating that soil mitigated the toxic effects of Cd. In soil amended with clay minerals, montmorillonite provided partial or total protection against fungistatic effects of Cd, whereas additions of kaolinite provided little or no protection. Growth rates of Aspergillus niger were inhibited to a greater extent by 100 or 250 mug of Cd per g in soil adjusted to pH 7.2 than in the same soil at its natural pH of 5.1. However, there were no differences in the growth rates of Aspergillus fischeri with 100 or 250 mug of Cd per g in the same soil, whether at pH 5.1 or adjusted to pH 7.2. Growth of A. niger and A. fischeri in a soil contaminated with a low concentration of Cd (i.e., 28 mug/g), obtained from a site near a Japanese smelter, did not differ significantly from growth in a soil collected some distance away and containing 4 mug of Cd per g. Growth of A. niger in sterile soil amended with 100 mug of Cd per g and inoculated with Bacillus cereus or Agrobacterium tumefaciens was reduced to a greater extent than in the same soil containing 100 mug of Cd per g but no bacteria. The inhibitory effects of Agrobacterium radiobacter to A. niger were slightly reduced in the presence of 100 mug of Cd per g, whereas the inhibitory effects of Serratia marcescens were enhanced.", "contents": "Effect of cadmium on fungi and on interactions between fungi and bacteria in soil: influence of clay minerals and pH. Fungi (Rhizopus stolonifer, Trichoderma viride, Fusarium oxysporum f. sp. conglutinans, Cunninghamella echinulata, and several species of Aspergillus and Penicillium) tolerated higher concentrations of cadmium (Cd) when grown in soil than when grown on laboratory media, indicating that soil mitigated the toxic effects of Cd. In soil amended with clay minerals, montmorillonite provided partial or total protection against fungistatic effects of Cd, whereas additions of kaolinite provided little or no protection. Growth rates of Aspergillus niger were inhibited to a greater extent by 100 or 250 mug of Cd per g in soil adjusted to pH 7.2 than in the same soil at its natural pH of 5.1. However, there were no differences in the growth rates of Aspergillus fischeri with 100 or 250 mug of Cd per g in the same soil, whether at pH 5.1 or adjusted to pH 7.2. Growth of A. niger and A. fischeri in a soil contaminated with a low concentration of Cd (i.e., 28 mug/g), obtained from a site near a Japanese smelter, did not differ significantly from growth in a soil collected some distance away and containing 4 mug of Cd per g. Growth of A. niger in sterile soil amended with 100 mug of Cd per g and inoculated with Bacillus cereus or Agrobacterium tumefaciens was reduced to a greater extent than in the same soil containing 100 mug of Cd per g but no bacteria. The inhibitory effects of Agrobacterium radiobacter to A. niger were slightly reduced in the presence of 100 mug of Cd per g, whereas the inhibitory effects of Serratia marcescens were enhanced."}
{"id": "PMID:18086", "title": "Significance of fecal coliform-positive Klebsiella.", "content": "A total of 191 Klebsiella pneumoniae isolates of human clinical, bovine mastitis, and a wide variety of environmental sources were tested for fecal coliform (FC) response with the membrane filtration and most probable number techniques. Twenty-seven Escherichia coli cultures of human clinical and environmental origins were also tested. Eighty-five percent (49/58) of known pathogenic K. pneumoniae were FC positive, compared with 16% (19/120) of the environmental strains. E. coli results indicated 93% (13/14) of the clinical and 85% (11/13) of the environmental strains as FC positive. There was no significant difference in the incidence of FC-positive cultures between pathogenic Klebsiella and E. coli. pH measurements of K. pneumoniae and E. coli cultures growing in m-FC broth at 44.5 degrees C revealed three distinct pH ranges correlating with colony morphology. beta-Galactosidase assays of Klebsiella and E. coli cultures at 44.5 degrees C indicated all were able to hydrolyze lactose, even if they were FC negative by the membrane filtration or most probable number techniques. The FC response pattern appears stable in K. pneumoniae. Three pathogenic cultures showed no change in FC responses after 270 generations of growth in sterile pulp mill effluent. Since K. pneumoniae is carried in the gastrointestinal tract of humans and animals and 85% of the tested pathogenic strains were FC positive, the isolation of FC-positive Klebsiella organisms from the environment would indicate their fecal or clinical origin or both. The added fact that K. pneumoniae is an opportunistic pathogen of increasing importance makes the occurrence of FC-positive environmental Klebsiella, particularly in large numbers, a potential human and animal health hazard.", "contents": "Significance of fecal coliform-positive Klebsiella. A total of 191 Klebsiella pneumoniae isolates of human clinical, bovine mastitis, and a wide variety of environmental sources were tested for fecal coliform (FC) response with the membrane filtration and most probable number techniques. Twenty-seven Escherichia coli cultures of human clinical and environmental origins were also tested. Eighty-five percent (49/58) of known pathogenic K. pneumoniae were FC positive, compared with 16% (19/120) of the environmental strains. E. coli results indicated 93% (13/14) of the clinical and 85% (11/13) of the environmental strains as FC positive. There was no significant difference in the incidence of FC-positive cultures between pathogenic Klebsiella and E. coli. pH measurements of K. pneumoniae and E. coli cultures growing in m-FC broth at 44.5 degrees C revealed three distinct pH ranges correlating with colony morphology. beta-Galactosidase assays of Klebsiella and E. coli cultures at 44.5 degrees C indicated all were able to hydrolyze lactose, even if they were FC negative by the membrane filtration or most probable number techniques. The FC response pattern appears stable in K. pneumoniae. Three pathogenic cultures showed no change in FC responses after 270 generations of growth in sterile pulp mill effluent. Since K. pneumoniae is carried in the gastrointestinal tract of humans and animals and 85% of the tested pathogenic strains were FC positive, the isolation of FC-positive Klebsiella organisms from the environment would indicate their fecal or clinical origin or both. The added fact that K. pneumoniae is an opportunistic pathogen of increasing importance makes the occurrence of FC-positive environmental Klebsiella, particularly in large numbers, a potential human and animal health hazard."}
{"id": "PMID:18087", "title": "Purification and characteristics of an alginase from Alginovibrio aquatilis.", "content": "An exocellular inducible alginase from a strain of Alginovibrio aquatilis was purified 61-fold by ammonium sulfate precipitation and column chromatography on Sephadex G-150 and diethylaminoethyl-cellulose. The purified enzyme was more resistant than the crude enzyme to elevated temperatures. The monovalent cations Cs+, Rb+, K+, Na+, and Li+, in order of decreasing enzyme activation, were required for activity. The pH optimum of the purified alginase was 8.0 and its molecular weight from exclusion chromatography on Sephadex G-150 was 110,000.", "contents": "Purification and characteristics of an alginase from Alginovibrio aquatilis. An exocellular inducible alginase from a strain of Alginovibrio aquatilis was purified 61-fold by ammonium sulfate precipitation and column chromatography on Sephadex G-150 and diethylaminoethyl-cellulose. The purified enzyme was more resistant than the crude enzyme to elevated temperatures. The monovalent cations Cs+, Rb+, K+, Na+, and Li+, in order of decreasing enzyme activation, were required for activity. The pH optimum of the purified alginase was 8.0 and its molecular weight from exclusion chromatography on Sephadex G-150 was 110,000."}
{"id": "PMID:18088", "title": "Concentration of enteroviruses from estuarine water.", "content": "Pleated cartridge filters readily adsorb viruses in estuarine water at low pH containing aluminum chloride. Adsorbed viruses are efficiently recovered by treating filters with glycine buffer at high pH. By using these procedures, it was possible to recover approximately 70% of the poliovirus added to 400 liters of estuarine water in 3 liters of filter eluate. Reconcentration of virus in the filter eluate in small volumes that are convenient for viral assays was more difficult. Reconcentration methods described previously for eluates from filters that process tap water or treated wastewater were inadequate when applied to eluates from filters used to process estuarine water containing large amounts of organic compounds. Two methods were found to permit efficient concentration of virus in filter eluates in small volumes. In both methods, virus in 3 liters of filter eluate was adsorbed to aluminum hydroxide flocs and then recovered in approximately 150 ml of buffered fetal calf serum. Additional reductions in volume were achieved by ultrafiltration or hydroextraction. By using these procedures 60 to 80% of the virus in 3 liters of filter eluate could be recovered in a final volume of 10 to 40 ml.", "contents": "Concentration of enteroviruses from estuarine water. Pleated cartridge filters readily adsorb viruses in estuarine water at low pH containing aluminum chloride. Adsorbed viruses are efficiently recovered by treating filters with glycine buffer at high pH. By using these procedures, it was possible to recover approximately 70% of the poliovirus added to 400 liters of estuarine water in 3 liters of filter eluate. Reconcentration of virus in the filter eluate in small volumes that are convenient for viral assays was more difficult. Reconcentration methods described previously for eluates from filters that process tap water or treated wastewater were inadequate when applied to eluates from filters used to process estuarine water containing large amounts of organic compounds. Two methods were found to permit efficient concentration of virus in filter eluates in small volumes. In both methods, virus in 3 liters of filter eluate was adsorbed to aluminum hydroxide flocs and then recovered in approximately 150 ml of buffered fetal calf serum. Additional reductions in volume were achieved by ultrafiltration or hydroextraction. By using these procedures 60 to 80% of the virus in 3 liters of filter eluate could be recovered in a final volume of 10 to 40 ml."}
{"id": "PMID:18116", "title": "Bucolome in prevention of hyperbilirubinaemia in preterm infants.", "content": "Fifty preterm babies were randomly assigned to a group given oral bucolome (30 mg/kg per day for 5 days) and a control group. Serum bilirubin levels of the treated infants from day 4 onwards were consistently lower than those of the control infants. 3 of the 25 control infants (but none of the 25 treated infants) had bilirubin levels greater than 18 mg/100 ml (308 mumol/l) and required exchange transfusion. No sedation or drowsiness was observed in the infants given bucolome, and though the drug caused some vomiting, weight gains were unaffected.", "contents": "Bucolome in prevention of hyperbilirubinaemia in preterm infants. Fifty preterm babies were randomly assigned to a group given oral bucolome (30 mg/kg per day for 5 days) and a control group. Serum bilirubin levels of the treated infants from day 4 onwards were consistently lower than those of the control infants. 3 of the 25 control infants (but none of the 25 treated infants) had bilirubin levels greater than 18 mg/100 ml (308 mumol/l) and required exchange transfusion. No sedation or drowsiness was observed in the infants given bucolome, and though the drug caused some vomiting, weight gains were unaffected."}
{"id": "PMID:18119", "title": "Prospective study of the Robertshaw endobronchial catheter in thoracic surgery.", "content": "One hundred three men undergoing thoracotomy on a general thoracic surgery service received endobronchial anesthesia with 100% oxygen using the Robertshaw tube. Bronchial intubation was accomplished in all. However, cross-leak or difficulty with deflation necessitated discontinuance in 8, while Pao2 values of 41 and 45 mm Hg caused abandonment in 2. There were no operative deaths. Surprisingly, hypoxemia in these patients related more to insufficient alveolar ventilation than to the venoarterial shunt.", "contents": "Prospective study of the Robertshaw endobronchial catheter in thoracic surgery. One hundred three men undergoing thoracotomy on a general thoracic surgery service received endobronchial anesthesia with 100% oxygen using the Robertshaw tube. Bronchial intubation was accomplished in all. However, cross-leak or difficulty with deflation necessitated discontinuance in 8, while Pao2 values of 41 and 45 mm Hg caused abandonment in 2. There were no operative deaths. Surprisingly, hypoxemia in these patients related more to insufficient alveolar ventilation than to the venoarterial shunt."}
{"id": "PMID:18125", "title": "[The cellulase enzyme system during growth and development of Acanthamoeba castellanii (author's transl)].", "content": "It could be shown that extracts of growing cultures of Acanthamoeba castellanii contained a cellulose degrading system. Reducing sugars are split off by one component of this system at an optimum of pH 4, another enzyme changes the viscosity at an optimum of pH 6, and a third component is a beta-glucosidase with an optimum at pH 3.5. At pH 4 the cellulose degradation products are cellobiose and glucose; at pH 6 higher molecular weight oligosaccharides are produced. During the development from trophozoites to cysts in a nutrient-free medium, the activities of both cellulases decline: Prior to the start of cellulose synthesis only 30%, and in cysts only 10% of the original existing activities are detectable. The biological function of the cellulase enzyme system is discussed together with a consideration of the fact that excystment takes place without digestion of the cyst wall in which the cellulose is deposited.", "contents": "[The cellulase enzyme system during growth and development of Acanthamoeba castellanii (author's transl)]. It could be shown that extracts of growing cultures of Acanthamoeba castellanii contained a cellulose degrading system. Reducing sugars are split off by one component of this system at an optimum of pH 4, another enzyme changes the viscosity at an optimum of pH 6, and a third component is a beta-glucosidase with an optimum at pH 3.5. At pH 4 the cellulose degradation products are cellobiose and glucose; at pH 6 higher molecular weight oligosaccharides are produced. During the development from trophozoites to cysts in a nutrient-free medium, the activities of both cellulases decline: Prior to the start of cellulose synthesis only 30%, and in cysts only 10% of the original existing activities are detectable. The biological function of the cellulase enzyme system is discussed together with a consideration of the fact that excystment takes place without digestion of the cyst wall in which the cellulose is deposited."}
{"id": "PMID:18126", "title": "Gamma glutamyl transpeptidase in colon cancer induced by 1,2-dimethylhydrazine.", "content": "The study of the gamma-glutamyl transpeptidase (GTase) in colon of adult rats showed that in the sequence: duodenum, jejunum, ileum, cecum and colon, the colon has the lowest activity. There are, on the other hand, relatively small differences between GTase activities in the ascending, transverse and descending portions of the large intestine. GTase activity in the colon of neonatal rat is several times higher than in the colon of adult rats. Colon adenocarcinoma induced by 1,2-dimethylhydrazine were found to have a much higher GTase activity than the homologous normal tissue. Because these tumors resemble human colonic adenocarcinomas, it is suggested that the assay of GTase levels of human colon mucosa might be of potential value in the diagnosis of neoplastic changes.", "contents": "Gamma glutamyl transpeptidase in colon cancer induced by 1,2-dimethylhydrazine. The study of the gamma-glutamyl transpeptidase (GTase) in colon of adult rats showed that in the sequence: duodenum, jejunum, ileum, cecum and colon, the colon has the lowest activity. There are, on the other hand, relatively small differences between GTase activities in the ascending, transverse and descending portions of the large intestine. GTase activity in the colon of neonatal rat is several times higher than in the colon of adult rats. Colon adenocarcinoma induced by 1,2-dimethylhydrazine were found to have a much higher GTase activity than the homologous normal tissue. Because these tumors resemble human colonic adenocarcinomas, it is suggested that the assay of GTase levels of human colon mucosa might be of potential value in the diagnosis of neoplastic changes."}
{"id": "PMID:18117", "title": "[A study on the behaviour of 7 serological parameters in many subjects affected by acute viral hepatitis (author's transl)].", "content": "The AA. have studied the behaviour of 7 serological parameters in 32 subjects affected by acute viral hapatitis, by means of 4 samples of blood performes at the distance of 12 days for the first and of 15 days for the others. The results are alike to these formerly knows, exception made for alkaline phosphatase, gamma Gt and immunoglobulines G and M.", "contents": "[A study on the behaviour of 7 serological parameters in many subjects affected by acute viral hepatitis (author's transl)]. The AA. have studied the behaviour of 7 serological parameters in 32 subjects affected by acute viral hapatitis, by means of 4 samples of blood performes at the distance of 12 days for the first and of 15 days for the others. The results are alike to these formerly knows, exception made for alkaline phosphatase, gamma Gt and immunoglobulines G and M."}
{"id": "PMID:18118", "title": "[Quantitative study and typization of aerobic bacteria in the conjunctival sacs of healthy eyes].", "content": "We carried out a qualitative and quantitative bacteriological research into the conjunctives of 220 subjects in good health mostly women (180) exempt from recent or previous eyes diseases. In order to gather conjunctival bacteria we employed with a few variations Hadley's et al. (1973 [12]) method. Among the calculated bacterial flora we found as the most numerous ones Staphylococcus epidermidis (mean valor 1960/ml), then Streptococci (480/ml), Micrococci (465/ml), Diphteroides (360/ml), Enterococci (77/ml) and numerous (700/ml) Gram-positives Cocci like Sarcina, Micrococcus tetragenes, Diplococcus, and very rarely bacterial genera Gram-negatives or Iphomycetes, also numerically inferior as regards the researches of other Authors, because owen study is carried by into eyes exempt from diseases.", "contents": "[Quantitative study and typization of aerobic bacteria in the conjunctival sacs of healthy eyes]. We carried out a qualitative and quantitative bacteriological research into the conjunctives of 220 subjects in good health mostly women (180) exempt from recent or previous eyes diseases. In order to gather conjunctival bacteria we employed with a few variations Hadley's et al. (1973 [12]) method. Among the calculated bacterial flora we found as the most numerous ones Staphylococcus epidermidis (mean valor 1960/ml), then Streptococci (480/ml), Micrococci (465/ml), Diphteroides (360/ml), Enterococci (77/ml) and numerous (700/ml) Gram-positives Cocci like Sarcina, Micrococcus tetragenes, Diplococcus, and very rarely bacterial genera Gram-negatives or Iphomycetes, also numerically inferior as regards the researches of other Authors, because owen study is carried by into eyes exempt from diseases."}
{"id": "PMID:18127", "title": "Isolation and properties of muscular glucose dehydrogenase (E.C. 1.1.1.47) from the stomachs of geese and ducks.", "content": "A method which purified 30-fold perparations of muscular glucose dehydrogenase from the stomachs of geese and ducks was elaborated. Activity of this enzyme was found to be dependent on presence of free-SH groups, NAD or NADP as coenzymes, and had an optimum at about pH 7-8. The enzyme's activity against 17 different monosaccharides and their derivatives was tested. The best substrate was beta-D-glucose, followed by D-glucose, D-glucosamine and D-xylose. Other compounds such as D-glucose-6-phosphate, D-fructose, D-mannose and 2-deoxyglucose were not oxidized. The enzyme preparation showed presence of enzymes which conduct gluconic acid metabolism.", "contents": "Isolation and properties of muscular glucose dehydrogenase (E.C. 1.1.1.47) from the stomachs of geese and ducks. A method which purified 30-fold perparations of muscular glucose dehydrogenase from the stomachs of geese and ducks was elaborated. Activity of this enzyme was found to be dependent on presence of free-SH groups, NAD or NADP as coenzymes, and had an optimum at about pH 7-8. The enzyme's activity against 17 different monosaccharides and their derivatives was tested. The best substrate was beta-D-glucose, followed by D-glucose, D-glucosamine and D-xylose. Other compounds such as D-glucose-6-phosphate, D-fructose, D-mannose and 2-deoxyglucose were not oxidized. The enzyme preparation showed presence of enzymes which conduct gluconic acid metabolism."}
{"id": "PMID:18128", "title": "Analgesic drugs in the management of pain.", "content": "The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated.", "contents": "Analgesic drugs in the management of pain. The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated."}
{"id": "PMID:18129", "title": "A sensitive method for gas-chromatographic assay of barbiturates in body fluids.", "content": "The Authors present a gas-chromatographic method which allows for the rapid identification and assay of barbiturates and antiepileptics in body fluids. The Kupferberger procedure for extraction is used. The identification is obtained on two different columns: 10% Dexil 300 GC on Chromosorb W-HP and 3% OV 17 on Chromosorb G AW-DMCS (80-100 mesh). A considerable and interesting reduction of the barbiturates adsorption in the columns is obtained by preliminary conditioning with tetraethylorthosilicate. In this way, phenobarbital and cyclobarbital may also be assayed up to 1 microgram/ml in blood. For the simultaneous assay of therapeutic levels of phenobarbital and hydrantoins methylderivates are better employed: blood concentrations as low as 0.1 microgram/ml are easily detected.", "contents": "A sensitive method for gas-chromatographic assay of barbiturates in body fluids. The Authors present a gas-chromatographic method which allows for the rapid identification and assay of barbiturates and antiepileptics in body fluids. The Kupferberger procedure for extraction is used. The identification is obtained on two different columns: 10% Dexil 300 GC on Chromosorb W-HP and 3% OV 17 on Chromosorb G AW-DMCS (80-100 mesh). A considerable and interesting reduction of the barbiturates adsorption in the columns is obtained by preliminary conditioning with tetraethylorthosilicate. In this way, phenobarbital and cyclobarbital may also be assayed up to 1 microgram/ml in blood. For the simultaneous assay of therapeutic levels of phenobarbital and hydrantoins methylderivates are better employed: blood concentrations as low as 0.1 microgram/ml are easily detected."}
{"id": "PMID:18130", "title": "Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation.", "content": "During aerobic incubation of trichloroethylene with rabbit liver microsomes and NADPH a difference absorption peak appears at 451-452 nm. Trichloroethylene does not form a ligand absorption spectrum with hepatic microsomes reduced by dithionite, or in anaerobic incubates in the presence of NADPH. Addition of trichloroethylene epoxide (2,2,3-trichloro-oxirane) to reduced suspensions of rabbit liver microsomes produces high difference absorption at 452 nm, the optical Ks being approximately 2 mM. Of all possible metabolites of trichloroethylene only trichloroethanol forms absorption in the vicinity of 480 nm, and the broad absorption band reveals relatively low absorption near 450 nm. Dichloroacetyl chloride is the main thermal rearrangement product of trichloroethylene epoxide, and also produces 452 nm absorption in reduced microsomes. However, the difference absorption is 5 times smaller than the absorption produced by the intermediate formed during incubation of trichloroethylene in metabolising liver microsomes. These observations include strong evidence for epoxide formation during microsomal oxidation of trichloroethylene. 14C-labelled trichloroethylene binds irreversibly to hepatic macromolecules in vivo and in vitro. Possible rearrangement pathways of 2,2,3-trichloro-oxirane and reactive intermediates are presented.", "contents": "Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation. During aerobic incubation of trichloroethylene with rabbit liver microsomes and NADPH a difference absorption peak appears at 451-452 nm. Trichloroethylene does not form a ligand absorption spectrum with hepatic microsomes reduced by dithionite, or in anaerobic incubates in the presence of NADPH. Addition of trichloroethylene epoxide (2,2,3-trichloro-oxirane) to reduced suspensions of rabbit liver microsomes produces high difference absorption at 452 nm, the optical Ks being approximately 2 mM. Of all possible metabolites of trichloroethylene only trichloroethanol forms absorption in the vicinity of 480 nm, and the broad absorption band reveals relatively low absorption near 450 nm. Dichloroacetyl chloride is the main thermal rearrangement product of trichloroethylene epoxide, and also produces 452 nm absorption in reduced microsomes. However, the difference absorption is 5 times smaller than the absorption produced by the intermediate formed during incubation of trichloroethylene in metabolising liver microsomes. These observations include strong evidence for epoxide formation during microsomal oxidation of trichloroethylene. 14C-labelled trichloroethylene binds irreversibly to hepatic macromolecules in vivo and in vitro. Possible rearrangement pathways of 2,2,3-trichloro-oxirane and reactive intermediates are presented."}
{"id": "PMID:18132", "title": "Inheritance of muscle and liver types of supernatant NADP-dependent isocitrate dehydrogenase in rainbow trout (Salmo gairdneri).", "content": "The genetics of allelic variation for NADP-dependent isocitrate dehydrogenase (IDH-s) found in the supernatant of liver and white muscle extracts of rainbow trout (Salmo gairdneri) was examined. Twenty progeny from each of 50 controlled matings were examined for IDH phenotypes. Progeny data clearly indicated that the IDH-s variation in the muscle is controlled by two loci--one fixed and one with two alleles producing molecules of different electrophoretic mobilities. IDH-s variation in the liver is controlled by two disomic loci which code for four alleles. No linkage between the loci controlling IDH-s in the liver and the loci controlling it in the muscle was detected.", "contents": "Inheritance of muscle and liver types of supernatant NADP-dependent isocitrate dehydrogenase in rainbow trout (Salmo gairdneri). The genetics of allelic variation for NADP-dependent isocitrate dehydrogenase (IDH-s) found in the supernatant of liver and white muscle extracts of rainbow trout (Salmo gairdneri) was examined. Twenty progeny from each of 50 controlled matings were examined for IDH phenotypes. Progeny data clearly indicated that the IDH-s variation in the muscle is controlled by two loci--one fixed and one with two alleles producing molecules of different electrophoretic mobilities. IDH-s variation in the liver is controlled by two disomic loci which code for four alleles. No linkage between the loci controlling IDH-s in the liver and the loci controlling it in the muscle was detected."}
{"id": "PMID:18133", "title": "Purification and properties of a new testosterone 17beta-dehydrogenase (NADP+) from guinea-pig liver.", "content": "As a result of studies of guinea-pig live testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), a new testosterone 17beta-dehydrogenase was discovered. The new enzyme was purified to a single homogeneous protein from the 105 000 g-supernatant fraction of guinea-pig liver by (NH4)2SO4 fractional precipitation and two gel-filtration stages, DEAE-cellulose column chromatography and hydroxyapatite column chromatography. It was characterized by many properties. The enzyme has almost the same properties as the classical testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), with respect to cofactor requirement, pH optima for dehydrogenation, effect of phosphate ion on the NAD+-dependent reaction and molecular weight, but characteristic differences were observed in substrate-specificity between the two dehydrogenases. With various androstane derivatives, the configuration of the A/B-ring junction was closely connected with enzyme activity. 5alpha-Androstanes, such as 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol and 17beta-hydroxy-5alpha-androstan-3-one, and 5beta-congeners, such as 5beta-androstane-3alpha,17beta-diol, 5beta-androstane-3beta,17beta-diol and 17beta-hydroxy-5beta-androstan-3-one, served as substrates for both the EC 1.1.1.64 enzyme and the new enzyme. The EC 1.1.1.64 enzyme oxidized testosterone more rapidly than did the new enzyme. These comparisons were based on the relative activities, apparent Km values and apparent Vmax values.", "contents": "Purification and properties of a new testosterone 17beta-dehydrogenase (NADP+) from guinea-pig liver. As a result of studies of guinea-pig live testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), a new testosterone 17beta-dehydrogenase was discovered. The new enzyme was purified to a single homogeneous protein from the 105 000 g-supernatant fraction of guinea-pig liver by (NH4)2SO4 fractional precipitation and two gel-filtration stages, DEAE-cellulose column chromatography and hydroxyapatite column chromatography. It was characterized by many properties. The enzyme has almost the same properties as the classical testosterone 17beta-dehydrogenase (NADP+) (EC 1.1.1.64), with respect to cofactor requirement, pH optima for dehydrogenation, effect of phosphate ion on the NAD+-dependent reaction and molecular weight, but characteristic differences were observed in substrate-specificity between the two dehydrogenases. With various androstane derivatives, the configuration of the A/B-ring junction was closely connected with enzyme activity. 5alpha-Androstanes, such as 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol and 17beta-hydroxy-5alpha-androstan-3-one, and 5beta-congeners, such as 5beta-androstane-3alpha,17beta-diol, 5beta-androstane-3beta,17beta-diol and 17beta-hydroxy-5beta-androstan-3-one, served as substrates for both the EC 1.1.1.64 enzyme and the new enzyme. The EC 1.1.1.64 enzyme oxidized testosterone more rapidly than did the new enzyme. These comparisons were based on the relative activities, apparent Km values and apparent Vmax values."}
{"id": "PMID:18134", "title": "Partial purification and properties of frog liver tyrosine aminotransferase.", "content": "Hepatic tyrosine aminotransferase of the frog Rana temporaria was partially purified by (NH4)2SO4 fractionation and successive chromatography on DEAE-cellulose DE-52, Ultrogel AcA-34, DEAE-cellulose DE-52 again and, finally, hydroxyapatite. During the last step, the enzyme activity separated into two fractions; traces of a third fraction were also found. The major form was purified 6000-fold to a specific activity of 200 units/mg of protein; it was about 50% pure by electrophoretic criteria. It had mol.wt. about 85 000 as determined by gel filtration on a Sephadex G-100 column. It was not activated by added pyridoxal 5'-phosphate. The enzyme was, however, inactivated by the pyridoxal phosphate reactants canaline and amino-oxyacetate. The enzyme was specific for 2-oxoglutarate as the amino group acceptor. Homogentisate inhibited the enzyme and adrenaline was an activator; both effects were seen at low concentrations of the effectors. The relationship between initial rate and tyrosine or 2-oxoglutarate concentration was abnormal and complex. Form-2 enzyme had similar or identical molecular weight, cofactor requirements, oxo acid specificity and kinetics.", "contents": "Partial purification and properties of frog liver tyrosine aminotransferase. Hepatic tyrosine aminotransferase of the frog Rana temporaria was partially purified by (NH4)2SO4 fractionation and successive chromatography on DEAE-cellulose DE-52, Ultrogel AcA-34, DEAE-cellulose DE-52 again and, finally, hydroxyapatite. During the last step, the enzyme activity separated into two fractions; traces of a third fraction were also found. The major form was purified 6000-fold to a specific activity of 200 units/mg of protein; it was about 50% pure by electrophoretic criteria. It had mol.wt. about 85 000 as determined by gel filtration on a Sephadex G-100 column. It was not activated by added pyridoxal 5'-phosphate. The enzyme was, however, inactivated by the pyridoxal phosphate reactants canaline and amino-oxyacetate. The enzyme was specific for 2-oxoglutarate as the amino group acceptor. Homogentisate inhibited the enzyme and adrenaline was an activator; both effects were seen at low concentrations of the effectors. The relationship between initial rate and tyrosine or 2-oxoglutarate concentration was abnormal and complex. Form-2 enzyme had similar or identical molecular weight, cofactor requirements, oxo acid specificity and kinetics."}
{"id": "PMID:18135", "title": "Characterization of an adenosine 3':5'-cyclic monophosphate phosphodiesterase from baker's yeast. Its binding to subcellular particles, catalytic properties and gel-filtration behaviour.", "content": "1. The 3':5'-cyclic AMP phosphodiesterase in the microsomal fraction of baker's yeast is highly specific for cyclic AMP, and not inhibited by cyclic GMP, cyclic IMP or cyclic UMP. Catalytic activity is abolished by 30 micrometer-EDTA. At 30 degrees C and pH8.1, the Km is 0.17 micrometer, and theophylline is a simple competitive inhibitor with Ki 0.7 micrometer. The pH optimum is about 7.8 at 0.25 micrometer-cyclic AMP, so that over the physiological range of pH in yeast the activity changes in the opposite direction to that of adenylate cyclase [PH optimum about 6.2; Londesborough & Nurminen (1972) Acta Chem. Scand. 26, 3396-3398].2. At pH 7.2, dissociation of the enzyme from dilute microsomal suspensions increased with ionic strength and was almost complete at 0.3 M-KCl. MgCl2 caused more dissociation than did KCl or NaCl at the same ionic strength, but at low KCl concentrations binding required small amounts of free bivalent metal ions. In 0.1 M-KCl the binding decreased between pH 4.7 and 9.3. At pH 7.2 the binding was independent of temperature between 5 and 20 degrees C. These observations suggest that the binding is electrostatic rather than hydrophobic. 3. The proportion of bound activity increased with the concentration of the microsomal fraction, and at 22 mg of protein/ml and pH 7.2 was 70% at I0.18, and 35% at I0.26. Presumably a substantial amount of the enzyme is particle-bound in vivo. 4. At 5 degrees C in 10 mM-potassium phosphate, pH 7.2, the apparent molecular weight of KCl-solubilized enzyme decreased with enzyme concentration from about 200 000 to 40 000. In the presence of 0.5M-KCl, a constant mol.wt. of about 55 000 was observed over a 20-fold range of enzyme concentrations.", "contents": "Characterization of an adenosine 3':5'-cyclic monophosphate phosphodiesterase from baker's yeast. Its binding to subcellular particles, catalytic properties and gel-filtration behaviour. 1. The 3':5'-cyclic AMP phosphodiesterase in the microsomal fraction of baker's yeast is highly specific for cyclic AMP, and not inhibited by cyclic GMP, cyclic IMP or cyclic UMP. Catalytic activity is abolished by 30 micrometer-EDTA. At 30 degrees C and pH8.1, the Km is 0.17 micrometer, and theophylline is a simple competitive inhibitor with Ki 0.7 micrometer. The pH optimum is about 7.8 at 0.25 micrometer-cyclic AMP, so that over the physiological range of pH in yeast the activity changes in the opposite direction to that of adenylate cyclase [PH optimum about 6.2; Londesborough & Nurminen (1972) Acta Chem. Scand. 26, 3396-3398].2. At pH 7.2, dissociation of the enzyme from dilute microsomal suspensions increased with ionic strength and was almost complete at 0.3 M-KCl. MgCl2 caused more dissociation than did KCl or NaCl at the same ionic strength, but at low KCl concentrations binding required small amounts of free bivalent metal ions. In 0.1 M-KCl the binding decreased between pH 4.7 and 9.3. At pH 7.2 the binding was independent of temperature between 5 and 20 degrees C. These observations suggest that the binding is electrostatic rather than hydrophobic. 3. The proportion of bound activity increased with the concentration of the microsomal fraction, and at 22 mg of protein/ml and pH 7.2 was 70% at I0.18, and 35% at I0.26. Presumably a substantial amount of the enzyme is particle-bound in vivo. 4. At 5 degrees C in 10 mM-potassium phosphate, pH 7.2, the apparent molecular weight of KCl-solubilized enzyme decreased with enzyme concentration from about 200 000 to 40 000. In the presence of 0.5M-KCl, a constant mol.wt. of about 55 000 was observed over a 20-fold range of enzyme concentrations."}
{"id": "PMID:18136", "title": "Physical and binding properties of large fragments of human serum albumin.", "content": "Three large fragments of human serum albumin were produced by peptic digestion of the native protein [Geisow & Beaven (1977) Biochem. J. 161, 619-625]. Fragment P44 represents residues 1-386 and fragments P29 and P31 represent residues 49-307 and residues 308-584 respectively of the albumin molecule. The large N-terminal fragment P44 has a similar percentage of alpha-helix to stored defatted albumin, although the alpha-helix content of all the fragments is significantly less than that of freshly prepared albumin. The fragment P44 appears to account for all the binding of the hydrophobic probe 8-anilinonaphthalene-1-sulphonate to albumin. N-Acetyl-L-tryptophan binds to this fragment and displaces one of the bound molecules of 8-anilinonaphthalene-1-sulphonate. Bilirubin binds to fragments P44 and P29, and the complexes show similar circular-dichroism spectra to that of the complex between bilirubin and whole albumin. These results are in  agreement with affinity-labeling work on albumin with reactive ligands where substitution occurs in the N-terminal region of the molecule. The sharp conformational transitional transition in albumin which is observed between pH4 and 3.5 was absent from the fragments. This isomerization, usually called the N-F transition, probably occurs in intact albumin as a result of the  unfolding or separation of the C-terminal third of the protein from the remainder of the molecule.", "contents": "Physical and binding properties of large fragments of human serum albumin. Three large fragments of human serum albumin were produced by peptic digestion of the native protein [Geisow & Beaven (1977) Biochem. J. 161, 619-625]. Fragment P44 represents residues 1-386 and fragments P29 and P31 represent residues 49-307 and residues 308-584 respectively of the albumin molecule. The large N-terminal fragment P44 has a similar percentage of alpha-helix to stored defatted albumin, although the alpha-helix content of all the fragments is significantly less than that of freshly prepared albumin. The fragment P44 appears to account for all the binding of the hydrophobic probe 8-anilinonaphthalene-1-sulphonate to albumin. N-Acetyl-L-tryptophan binds to this fragment and displaces one of the bound molecules of 8-anilinonaphthalene-1-sulphonate. Bilirubin binds to fragments P44 and P29, and the complexes show similar circular-dichroism spectra to that of the complex between bilirubin and whole albumin. These results are in  agreement with affinity-labeling work on albumin with reactive ligands where substitution occurs in the N-terminal region of the molecule. The sharp conformational transitional transition in albumin which is observed between pH4 and 3.5 was absent from the fragments. This isomerization, usually called the N-F transition, probably occurs in intact albumin as a result of the  unfolding or separation of the C-terminal third of the protein from the remainder of the molecule."}
{"id": "PMID:18137", "title": "Purification and properties of urease from bovine rumen.", "content": "Urease (urea amidohydrolase, EC 3.5.1.5) was extracted from the mixed rumen bacterial fraction of bovine rumen contents and purified 60-fold by (NH4)2SO4 precipitation, calcium phosphate-gel adsorption and chromatography on hydroxyapatite. The purified enzyme had maximum activity at pH 8.0. The molecular weight was estimated to be 120000-130000. The Km for urea was 8.3 X 10(-4) M+/-1.7 X 10(-4) M. The maximum velocity was 3.2+/-0.25 mmol of urea hydrolysed/h per mg of protein. The enzyme was stabilized by 50 mM-dithiothreitol. The enzyme was not inhibited by high concentrations of EDTA or phosphate but was inhibited by Mn2+, Mg2+, Ba2+, Hg2+, Cu2+, Zn2+, Cd2+, Ni2+ and Co2+. p-Chloromercuribenzenesulfphonate and N-ethylmaleimide inhibited the enzyme almost completely at 0.1 mM. Hydroxyurea and acetohydroxamate reversibly inhibited the enzyme. Polyacrylamide-gel electrophoresis showed that the mixed rumen bacteria produce ureases which have identical molecular weights and electrophoretic mobility. No multiple forms of urease were detected.", "contents": "Purification and properties of urease from bovine rumen. Urease (urea amidohydrolase, EC 3.5.1.5) was extracted from the mixed rumen bacterial fraction of bovine rumen contents and purified 60-fold by (NH4)2SO4 precipitation, calcium phosphate-gel adsorption and chromatography on hydroxyapatite. The purified enzyme had maximum activity at pH 8.0. The molecular weight was estimated to be 120000-130000. The Km for urea was 8.3 X 10(-4) M+/-1.7 X 10(-4) M. The maximum velocity was 3.2+/-0.25 mmol of urea hydrolysed/h per mg of protein. The enzyme was stabilized by 50 mM-dithiothreitol. The enzyme was not inhibited by high concentrations of EDTA or phosphate but was inhibited by Mn2+, Mg2+, Ba2+, Hg2+, Cu2+, Zn2+, Cd2+, Ni2+ and Co2+. p-Chloromercuribenzenesulfphonate and N-ethylmaleimide inhibited the enzyme almost completely at 0.1 mM. Hydroxyurea and acetohydroxamate reversibly inhibited the enzyme. Polyacrylamide-gel electrophoresis showed that the mixed rumen bacteria produce ureases which have identical molecular weights and electrophoretic mobility. No multiple forms of urease were detected."}
{"id": "PMID:18138", "title": "Adenosine triphosphate-activated adenylate deaminase from marine invertebrate animals. Properties of the enzyme from lugworm (Arenicola cristata) body-wall muscle.", "content": "Adenylate deaminase (AMP aminohydrolase, EC 3.5.4.6) from lugworm (Arenicola cristata) body-wall muscle was partially purified by extraction in KCl solutions and chromatography on phosphocellulose. Enzyme activity was eluted from the column at two salt concentrations. Both forms show co-operative binding of AMP (Hill coefficient, h, 2.85) with s0.5 values of 20 mM and 15.6 mM. ATP and ADP act as positive effectors lowering h to 1.07 and s0.5 to 2mM. The apparent Ka (activation) for ATP was 1.5mM. GTP is an inhibitor with an apparent Ki of 0.12 mM. In vivo the ATP-activated adenylate deaminase is in the active form and may be regulated by changes in GTP concentrations. Adenylate deaminase may act as a primary ammonia-forming enzyme in ammonotelic marine invertebrates with the purine nucleotide cycle.", "contents": "Adenosine triphosphate-activated adenylate deaminase from marine invertebrate animals. Properties of the enzyme from lugworm (Arenicola cristata) body-wall muscle. Adenylate deaminase (AMP aminohydrolase, EC 3.5.4.6) from lugworm (Arenicola cristata) body-wall muscle was partially purified by extraction in KCl solutions and chromatography on phosphocellulose. Enzyme activity was eluted from the column at two salt concentrations. Both forms show co-operative binding of AMP (Hill coefficient, h, 2.85) with s0.5 values of 20 mM and 15.6 mM. ATP and ADP act as positive effectors lowering h to 1.07 and s0.5 to 2mM. The apparent Ka (activation) for ATP was 1.5mM. GTP is an inhibitor with an apparent Ki of 0.12 mM. In vivo the ATP-activated adenylate deaminase is in the active form and may be regulated by changes in GTP concentrations. Adenylate deaminase may act as a primary ammonia-forming enzyme in ammonotelic marine invertebrates with the purine nucleotide cycle."}
{"id": "PMID:18139", "title": "Multiple alpha-mannosidase activities in mammalian tissues as shown by metal-ion activation.", "content": "1. Four different types of alpha-mannosidase activity were shown to occur in several tissues from the rat. There is the Zn2+-dependent enzyme, active at acidic pH, and three enzymes that are active near to neutral pH. 2. The 'neutral' enzymes are activated by Fe2+, Co2+ or Mn2+. 3. Optimum activities for these three enzymes are shown at pH values of 5.2, 6.5 and 7.3. The activity at pH6.5 is the only one evident without metal-ion activation, but activity is enhanced by all three metal ions. The activity at pH 5.2 is seen only in the presence of Fe2+ or Co2+, and the activity at pH7.3 is seen only in the presence of Co2+ or Mn2+ and in a non-chelating buffer medium. 4. The pH6.5-active enzyme is inactivated by EDTA, but activity is restored by excess of metal ion. 5. The enzymes differ markedly in their stability. The pH6.5-active enzyme is very labile and the pH7.3-active enzyme is the most stable. 6. Tissue preparations vary widely in their activity at pH6.5, but where activity is low it can be increased by incubation with one of the activating metal cations. 7. All the enzymes active at neutral pH are inhibited by heavy-metal ions and stabilized to some extent by thiol groups.", "contents": "Multiple alpha-mannosidase activities in mammalian tissues as shown by metal-ion activation. 1. Four different types of alpha-mannosidase activity were shown to occur in several tissues from the rat. There is the Zn2+-dependent enzyme, active at acidic pH, and three enzymes that are active near to neutral pH. 2. The 'neutral' enzymes are activated by Fe2+, Co2+ or Mn2+. 3. Optimum activities for these three enzymes are shown at pH values of 5.2, 6.5 and 7.3. The activity at pH6.5 is the only one evident without metal-ion activation, but activity is enhanced by all three metal ions. The activity at pH 5.2 is seen only in the presence of Fe2+ or Co2+, and the activity at pH7.3 is seen only in the presence of Co2+ or Mn2+ and in a non-chelating buffer medium. 4. The pH6.5-active enzyme is inactivated by EDTA, but activity is restored by excess of metal ion. 5. The enzymes differ markedly in their stability. The pH6.5-active enzyme is very labile and the pH7.3-active enzyme is the most stable. 6. Tissue preparations vary widely in their activity at pH6.5, but where activity is low it can be increased by incubation with one of the activating metal cations. 7. All the enzymes active at neutral pH are inhibited by heavy-metal ions and stabilized to some extent by thiol groups."}
{"id": "PMID:18140", "title": "Specific labelling of a constituent polypeptide of bovine heart mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone reductase by the inhibitor diphenyleneiodonium.", "content": "1. NADH-ubiquinone-1 and NADH-menadione reductase activities of Complex I were inhibited by diphenyleneiodonium (apparent Ki 23 and 30 nmol/mg of protein respectively). Reduction of K3Fe(CN)6 and juglone was relatively unaffected. 2. Iodoniumdiphenyl and derivatives were much less effective inhibitors. Compounds with similar ring structures to diphenyleneiodonium, in particular dibenzofuran, were inhibitors of NADH-ubiquinone-1 oxidoreductase. 3. Diphenylene[125I]iodonium specifically labelled a polypeptide of mol.wt. 23500. Maximum incorporation was 1 mol/mol of Complex-I flavin or 1 mol/mol of the 23500-mol.wt. polypeptide. 4. The label associated with this polypeptide was of limited stability, especially at lower pH. 5. Complete inhibition of ubiquinone reduction was achieved when 1 mol of inhibitor was incorporated/mol of Complex-I flavin, but the relationship between inhibition and labelling was not linear. 6. No evidence for covalent interaction between diphenyleneiodonium and the phospholipids of Complex I was obtained. 7. Rotenone increased the apparent affinity of diphenyleneiodonium for the 23500-mol.wt. polypeptide without affecting the maximum incorporation. 8. The 23500-mol.wt. polypeptide was not solubilized by chaotropic agents. Prior treatment of Complex I with chaotropic agents or sodium dodecyl sulphate prevented incorporation of diphenyleneiodonium into this polypeptide.", "contents": "Specific labelling of a constituent polypeptide of bovine heart mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone reductase by the inhibitor diphenyleneiodonium. 1. NADH-ubiquinone-1 and NADH-menadione reductase activities of Complex I were inhibited by diphenyleneiodonium (apparent Ki 23 and 30 nmol/mg of protein respectively). Reduction of K3Fe(CN)6 and juglone was relatively unaffected. 2. Iodoniumdiphenyl and derivatives were much less effective inhibitors. Compounds with similar ring structures to diphenyleneiodonium, in particular dibenzofuran, were inhibitors of NADH-ubiquinone-1 oxidoreductase. 3. Diphenylene[125I]iodonium specifically labelled a polypeptide of mol.wt. 23500. Maximum incorporation was 1 mol/mol of Complex-I flavin or 1 mol/mol of the 23500-mol.wt. polypeptide. 4. The label associated with this polypeptide was of limited stability, especially at lower pH. 5. Complete inhibition of ubiquinone reduction was achieved when 1 mol of inhibitor was incorporated/mol of Complex-I flavin, but the relationship between inhibition and labelling was not linear. 6. No evidence for covalent interaction between diphenyleneiodonium and the phospholipids of Complex I was obtained. 7. Rotenone increased the apparent affinity of diphenyleneiodonium for the 23500-mol.wt. polypeptide without affecting the maximum incorporation. 8. The 23500-mol.wt. polypeptide was not solubilized by chaotropic agents. Prior treatment of Complex I with chaotropic agents or sodium dodecyl sulphate prevented incorporation of diphenyleneiodonium into this polypeptide."}
{"id": "PMID:18141", "title": "Changes in the kinetic behaviour of threonine transport into Trypanosoma brucei elicited by variation in hydrogen ion concentration.", "content": "1. The dependence of V and V/K(m) for threonine transport into Trypanosoma brucei upon the external concentration of H(+) was studied. 2. Two ionizing groups, the alpha-amino group of the substrate and a group at the substrate-binding site of the carrier, were found to influence the observed kinetic behaviour of transport. 3. The pK of the group at the substrate-binding site on the free carrier was found to be 6.95 at 30 degrees C and to be temperature-dependent; its heat of ionization was -63.8kJ, which is outside the range for most proton dissociations and suggests a significant contribution from some other source, possibly the remainder of the carrier or the membrane environment. 4. Binding of substrate caused the pK of its alpha-amino group to shift to a higher value, whereas that of the carrier group shifted to a lower value (6.65 at 30 degrees C). 5. The ionic interaction between substrate and carrier appeared to be involved in the stabilizing of the protonated substrate and the species of the carrier-substrate complex required for the membrane-translocation step. 6. The same ionic species of carrier-substrate complex is required for both substrate dissociation and translocation of the substrate through the membrane. 7. H(+) symport or antiport did not occur during threonine uptake.", "contents": "Changes in the kinetic behaviour of threonine transport into Trypanosoma brucei elicited by variation in hydrogen ion concentration. 1. The dependence of V and V/K(m) for threonine transport into Trypanosoma brucei upon the external concentration of H(+) was studied. 2. Two ionizing groups, the alpha-amino group of the substrate and a group at the substrate-binding site of the carrier, were found to influence the observed kinetic behaviour of transport. 3. The pK of the group at the substrate-binding site on the free carrier was found to be 6.95 at 30 degrees C and to be temperature-dependent; its heat of ionization was -63.8kJ, which is outside the range for most proton dissociations and suggests a significant contribution from some other source, possibly the remainder of the carrier or the membrane environment. 4. Binding of substrate caused the pK of its alpha-amino group to shift to a higher value, whereas that of the carrier group shifted to a lower value (6.65 at 30 degrees C). 5. The ionic interaction between substrate and carrier appeared to be involved in the stabilizing of the protonated substrate and the species of the carrier-substrate complex required for the membrane-translocation step. 6. The same ionic species of carrier-substrate complex is required for both substrate dissociation and translocation of the substrate through the membrane. 7. H(+) symport or antiport did not occur during threonine uptake."}
{"id": "PMID:18142", "title": "Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities.", "content": "1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis.", "contents": "Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities. 1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. ;Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis."}
{"id": "PMID:18143", "title": "The mechanism of inhibition by acidosis of gluconeogenesis from lactate in rat liver.", "content": "1. Gluconeogenesis from lactate or pyruvate was studied in perfused livers from starved rats at perfusate pH7.4 or under conditions simulating uncompensated metabolic acidosis (perfusate pH6.7-6.8). 2. In 'acidotic' perfusions gluconeogenesis and uptake of lactate or pyruvate were decreased. 3. Measurement of hepatic intermediate metabolites suggested that the effect of acidosis was exerted at a stage preceding phosphoenolpyruvate. 4. Total intracellular oxaloacetate concentration was significantly decreased in the acidotic livers perfused with lactate. 5. It is suggested that decreased gluconeogenesis in acidosis is due to substrate limitation of phosphoenolypyruvate carboxykinase. 6. The possible reasons for the fall in oxaloacetate concentration in acidotic livers are discussed; two of the more likely mechanisms are inhibition of the pyruvate carboxylase system and a change in the [malate]/[oxaloacetate] ratio due to the fall in intracellular pH.", "contents": "The mechanism of inhibition by acidosis of gluconeogenesis from lactate in rat liver. 1. Gluconeogenesis from lactate or pyruvate was studied in perfused livers from starved rats at perfusate pH7.4 or under conditions simulating uncompensated metabolic acidosis (perfusate pH6.7-6.8). 2. In 'acidotic' perfusions gluconeogenesis and uptake of lactate or pyruvate were decreased. 3. Measurement of hepatic intermediate metabolites suggested that the effect of acidosis was exerted at a stage preceding phosphoenolpyruvate. 4. Total intracellular oxaloacetate concentration was significantly decreased in the acidotic livers perfused with lactate. 5. It is suggested that decreased gluconeogenesis in acidosis is due to substrate limitation of phosphoenolypyruvate carboxykinase. 6. The possible reasons for the fall in oxaloacetate concentration in acidotic livers are discussed; two of the more likely mechanisms are inhibition of the pyruvate carboxylase system and a change in the [malate]/[oxaloacetate] ratio due to the fall in intracellular pH."}
{"id": "PMID:18144", "title": "Proton translocation coupled to electron flow from endogenous substrates to fumarate in anaerobically grown Escherichia coli K12.", "content": "Observed leads to H+/2e- values for proton translocation during the reduction of fumarate by endogenous substrates in anaerobic cells of Escherichia coli K12 varied with fumarate concentration. This variation was probably due mainly to incomplete fumarate utilization. Under optimum conditions a minimum value for leads to H+/2e- of 1.04+/-0.20 was obtained.", "contents": "Proton translocation coupled to electron flow from endogenous substrates to fumarate in anaerobically grown Escherichia coli K12. Observed leads to H+/2e- values for proton translocation during the reduction of fumarate by endogenous substrates in anaerobic cells of Escherichia coli K12 varied with fumarate concentration. This variation was probably due mainly to incomplete fumarate utilization. Under optimum conditions a minimum value for leads to H+/2e- of 1.04+/-0.20 was obtained."}
{"id": "PMID:18145", "title": "Effects of starvation and development on mitochondrial acetoacetyl-coenzyme A thiolase of rat liver.", "content": "The activity of the putative ketogenic beta-oxoacyl-CoA thiolase from mitochondria of rat liver increases with starvation, during neonatal life, and after the injection of glucagon. These changes are associated with alteration in ketonaemia. The changes in activities of this species of thiolase are not associated with significant alterations in the apparent affinity (Km) for the ketogenic substrate, acetyl-CoA. These results support a role for thiolase in the regulation of ketogenesis.", "contents": "Effects of starvation and development on mitochondrial acetoacetyl-coenzyme A thiolase of rat liver. The activity of the putative ketogenic beta-oxoacyl-CoA thiolase from mitochondria of rat liver increases with starvation, during neonatal life, and after the injection of glucagon. These changes are associated with alteration in ketonaemia. The changes in activities of this species of thiolase are not associated with significant alterations in the apparent affinity (Km) for the ketogenic substrate, acetyl-CoA. These results support a role for thiolase in the regulation of ketogenesis."}
{"id": "PMID:18146", "title": "Guanylate cyclase activity and cyclic nucleotide concentrations during liver regeneration after experimental injury.", "content": "Cyclic nucleotide concentrations and guanylate cyclase activity were measured in regenerating rat liver. Previous work has shown that in livers of partially hepatectomized rats the activity of a membrane-bound guanylate cyclase increases considerably during the early replicative phase [Kimura & Murad (1975) Proc. Natl. Acad. Sci. U.S.A.72, 1965-1969; Goridis & Reutter (1975) Nature (London) 257, 698-700]. Over the same time period after partial hepatectomy, increased tissue concentrations of cyclic GMP were found when the rats were killed under pentobarbital anaesthesia, but not when anaesthesia was omitted. The results obtained on hepatectomized livers were compared with the changes in guanylate cyclase activity and cyclic nucleotide concentrations during the response to galactosamine treatment. Here, a peak of guanylate cyclase activity and of cyclic GMP concentrations occurred at 8h, that is before the beginning of the proliferative response. Both parameters were normal at the time of increased DNA synthesis. There does not, therefore, seem to be a consistent correlation between changes in guanylate cyclase activity or concentrations of cyclic GMP and an increase in liver DNA synthesis. A modest rise in cyclic AMP concentrations was found, however, in livers of galactosamine-treated rats, which was coincident with the time of DNA synthesis.", "contents": "Guanylate cyclase activity and cyclic nucleotide concentrations during liver regeneration after experimental injury. Cyclic nucleotide concentrations and guanylate cyclase activity were measured in regenerating rat liver. Previous work has shown that in livers of partially hepatectomized rats the activity of a membrane-bound guanylate cyclase increases considerably during the early replicative phase [Kimura & Murad (1975) Proc. Natl. Acad. Sci. U.S.A.72, 1965-1969; Goridis & Reutter (1975) Nature (London) 257, 698-700]. Over the same time period after partial hepatectomy, increased tissue concentrations of cyclic GMP were found when the rats were killed under pentobarbital anaesthesia, but not when anaesthesia was omitted. The results obtained on hepatectomized livers were compared with the changes in guanylate cyclase activity and cyclic nucleotide concentrations during the response to galactosamine treatment. Here, a peak of guanylate cyclase activity and of cyclic GMP concentrations occurred at 8h, that is before the beginning of the proliferative response. Both parameters were normal at the time of increased DNA synthesis. There does not, therefore, seem to be a consistent correlation between changes in guanylate cyclase activity or concentrations of cyclic GMP and an increase in liver DNA synthesis. A modest rise in cyclic AMP concentrations was found, however, in livers of galactosamine-treated rats, which was coincident with the time of DNA synthesis."}
{"id": "PMID:18147", "title": "Catecholamine-sensitive adenylate cyclase of caudate nucleus and cerebral cortex. Effects of guanine nucleotides.", "content": "1. GTP and GMP-P(NH)P (guanyl-5'-yl imidodiphosphate) were observed to increase the stimulation of neural adenylate cyclase by dopamine (3,4-dihydroxyphenethylamine) and noradrenaline. 2. GMP-P(NH)P had a biphasic effect on the enzyme activity. 3. Preincubation of membranes with GMP-P(NH)P activated the enzyme by a process dependent on time and temperature. Catecholamines increased the speed and the extent of this activation. 4. Membrane fractions contained high- and low-affinity sites for GMP-P(NH)P binding: this binding was due to protein(s) of the membrane preparations. 5. Low-affinity-site binding of GMP-P(NH)P appeared to be related to the stimulatory effect on the adenylate cyclase activity.", "contents": "Catecholamine-sensitive adenylate cyclase of caudate nucleus and cerebral cortex. Effects of guanine nucleotides. 1. GTP and GMP-P(NH)P (guanyl-5'-yl imidodiphosphate) were observed to increase the stimulation of neural adenylate cyclase by dopamine (3,4-dihydroxyphenethylamine) and noradrenaline. 2. GMP-P(NH)P had a biphasic effect on the enzyme activity. 3. Preincubation of membranes with GMP-P(NH)P activated the enzyme by a process dependent on time and temperature. Catecholamines increased the speed and the extent of this activation. 4. Membrane fractions contained high- and low-affinity sites for GMP-P(NH)P binding: this binding was due to protein(s) of the membrane preparations. 5. Low-affinity-site binding of GMP-P(NH)P appeared to be related to the stimulatory effect on the adenylate cyclase activity."}
{"id": "PMID:18157", "title": "Cardiac action of carazolol and methypranol in comparison with other beta-receptor blockers.", "content": "The new beta-blockers 4-(2-hydroxy-3-isopropyl-amino-propoxy)-carbazole (carazolol) and 1-(4-acetoxy-2,3,5-trimethylphenyloxy)-3-isopropylamino-propan-2-ol (methypranol, Disorat) were compared with 14 well-known beta-blocking agents with regard to isoproterenol antagonism (equipotent doses in the rabbit i.v.), acute toxicity (LD50 in mice i.v.) and intrinsic sympathomimetic activity (increase in the heart rate of reserpinized rats i.p.). The following descending order for the equipotent beta-receptor blocking doses was obtained: nifenalol, DCI, pronethalol, practolol, sotalol, alprenolol, bupranolol, toliprolol, propranolol, methypranol, YB 2 pindolol, bunitrolol, oxprenolol, bunolol and carazolol. Carazolol had, in addition, the highest therapeutic index and at beta-receptor blocking doses virtually no intrinsic sympathomimetic activity.", "contents": "Cardiac action of carazolol and methypranol in comparison with other beta-receptor blockers. The new beta-blockers 4-(2-hydroxy-3-isopropyl-amino-propoxy)-carbazole (carazolol) and 1-(4-acetoxy-2,3,5-trimethylphenyloxy)-3-isopropylamino-propan-2-ol (methypranol, Disorat) were compared with 14 well-known beta-blocking agents with regard to isoproterenol antagonism (equipotent doses in the rabbit i.v.), acute toxicity (LD50 in mice i.v.) and intrinsic sympathomimetic activity (increase in the heart rate of reserpinized rats i.p.). The following descending order for the equipotent beta-receptor blocking doses was obtained: nifenalol, DCI, pronethalol, practolol, sotalol, alprenolol, bupranolol, toliprolol, propranolol, methypranol, YB 2 pindolol, bunitrolol, oxprenolol, bunolol and carazolol. Carazolol had, in addition, the highest therapeutic index and at beta-receptor blocking doses virtually no intrinsic sympathomimetic activity."}
{"id": "PMID:18158", "title": "Bufuralol, a new beta-adrenoceptor blocking agent. Part 1: synthesis and structure-activity studies in a series of benzofuran-2-ethanolamines.", "content": "The synthesis and resolution of a new beta-adrenoceptor blocking agent, 1-(7-ethylbenzofuran-2-yl)-2-tert.-butylamino-1-hydroxyethane (bufuralol) are described. Structure-activity studies leading to selection of the title compound are discussed.", "contents": "Bufuralol, a new beta-adrenoceptor blocking agent. Part 1: synthesis and structure-activity studies in a series of benzofuran-2-ethanolamines. The synthesis and resolution of a new beta-adrenoceptor blocking agent, 1-(7-ethylbenzofuran-2-yl)-2-tert.-butylamino-1-hydroxyethane (bufuralol) are described. Structure-activity studies leading to selection of the title compound are discussed."}
{"id": "PMID:18162", "title": "Studies on the biosynthesis of 16-membered macrolide antibiotics using carbon-13 nuclear magnetic resonance spectroscopy.", "content": "The origin of the skeletal carbons in the lactone ring of 16-membered macrolide antiobiotics has been studied. 13C-labeled antibiotics leucomycin and tylosin, have been obtained from the culture broth of Streptomyces kitasatoensis 66-14-3 and Streptomyces fradiae C-373, respectively in the presence of appropriate 13C-labeled precursors, and 13C NMR spectra of the antibiotics thus obtained have been measured. It was shown that the aglycone of leucomycin A3 is derived from five acetates, one propionate, one butyrate, and an unknown precursor corresponding to two carbons. The formyl carbon which is characteristic of the basic 16-membered macrolides orginates from C-4 butyrate. On the other hand, the aglycone of tylosin is formed from two acetates, five propionates and one butyrate. Butyric acid and ethylmalonic acid are metabolized to propionyl-CoA or methylmolonyl-CoA through a pathway involving methylmalonyl-CoA mutase, and subsequently incorporated into the lactone ring of tylosin.", "contents": "Studies on the biosynthesis of 16-membered macrolide antibiotics using carbon-13 nuclear magnetic resonance spectroscopy. The origin of the skeletal carbons in the lactone ring of 16-membered macrolide antiobiotics has been studied. 13C-labeled antibiotics leucomycin and tylosin, have been obtained from the culture broth of Streptomyces kitasatoensis 66-14-3 and Streptomyces fradiae C-373, respectively in the presence of appropriate 13C-labeled precursors, and 13C NMR spectra of the antibiotics thus obtained have been measured. It was shown that the aglycone of leucomycin A3 is derived from five acetates, one propionate, one butyrate, and an unknown precursor corresponding to two carbons. The formyl carbon which is characteristic of the basic 16-membered macrolides orginates from C-4 butyrate. On the other hand, the aglycone of tylosin is formed from two acetates, five propionates and one butyrate. Butyric acid and ethylmalonic acid are metabolized to propionyl-CoA or methylmolonyl-CoA through a pathway involving methylmalonyl-CoA mutase, and subsequently incorporated into the lactone ring of tylosin."}
{"id": "PMID:18166", "title": "Interaction of the aldolase and the membrane of human erythrocytes.", "content": "Up to 80% of cellular aldolase (EC 4.1.2.13) was retained in the membrane fraction isolated following hemolysis of human erythrocytes under appropriate conditions. Binding was reversed by increasing the pH and ionic strength. Millimolar levels of the substrate, fructose 1,6-bisphosphate, selectively eluted aldolase from the membrane, while related metabolites did not. Using the membrane as a high affinity adsorbant, electrophoretically pure aldolase of high specific activity was prepared in high yield. The reassociation of pure aldolase and membranes was characterized. The sole site of human erythrocyte aldolase binding was shown to be the cytoplasmic surface domain of band 3, the predominant membrane-spanning polypeptide. One aldolase molecule was bound per band 3 polypeptide. Upon binding to either whole membranes, solubilized band 3, or proteolytic fragments from the cytoplasmic surface pole of band 3, aldolase underwent a profound loss of catalytic activity, reversed by raising the substrate concentration.", "contents": "Interaction of the aldolase and the membrane of human erythrocytes. Up to 80% of cellular aldolase (EC 4.1.2.13) was retained in the membrane fraction isolated following hemolysis of human erythrocytes under appropriate conditions. Binding was reversed by increasing the pH and ionic strength. Millimolar levels of the substrate, fructose 1,6-bisphosphate, selectively eluted aldolase from the membrane, while related metabolites did not. Using the membrane as a high affinity adsorbant, electrophoretically pure aldolase of high specific activity was prepared in high yield. The reassociation of pure aldolase and membranes was characterized. The sole site of human erythrocyte aldolase binding was shown to be the cytoplasmic surface domain of band 3, the predominant membrane-spanning polypeptide. One aldolase molecule was bound per band 3 polypeptide. Upon binding to either whole membranes, solubilized band 3, or proteolytic fragments from the cytoplasmic surface pole of band 3, aldolase underwent a profound loss of catalytic activity, reversed by raising the substrate concentration."}
{"id": "PMID:18169", "title": "The effect of calcium on the respiratory responses of mung bean mitochondria.", "content": "Purified mung bean hypocotyl mitochondria were examined for their capacity to carry out respiration-dependent accumulation of calcium. The addition of 0.1-1.0 mM calcium to mung bean mitochondria supplemented with succinate gave no stimulation of state 4 respiration even in the presence of inorganic phosphate and the ionophoretic antibiotic A-23187. Even at high calcium concentrations, no transient changes in the respiratory activity occurred and subsequent addition of ADP initiated a further state 3 response. Although the additions of calcium resulted in a rapid H+ ejection, it was insensitive to lanthanum and uncoupling agents. Similarly, additions of calcium failed to initiate any transient changes in the oxidation-reduction states of either pyridine nucleotides or cytochrome b. Direct spectrophotometric recordings of absorbance changes of murexide revealed no respiration-linked calcium transport. It is proposed that although mung bean mitochondria possess a respiration-linked electrochemical potential gradient it would appear that this potential cannot be expressed as calcium transport even at high ion concentrations, probably due to a low calcium membrane permeability.", "contents": "The effect of calcium on the respiratory responses of mung bean mitochondria. Purified mung bean hypocotyl mitochondria were examined for their capacity to carry out respiration-dependent accumulation of calcium. The addition of 0.1-1.0 mM calcium to mung bean mitochondria supplemented with succinate gave no stimulation of state 4 respiration even in the presence of inorganic phosphate and the ionophoretic antibiotic A-23187. Even at high calcium concentrations, no transient changes in the respiratory activity occurred and subsequent addition of ADP initiated a further state 3 response. Although the additions of calcium resulted in a rapid H+ ejection, it was insensitive to lanthanum and uncoupling agents. Similarly, additions of calcium failed to initiate any transient changes in the oxidation-reduction states of either pyridine nucleotides or cytochrome b. Direct spectrophotometric recordings of absorbance changes of murexide revealed no respiration-linked calcium transport. It is proposed that although mung bean mitochondria possess a respiration-linked electrochemical potential gradient it would appear that this potential cannot be expressed as calcium transport even at high ion concentrations, probably due to a low calcium membrane permeability."}
{"id": "PMID:18170", "title": "A simple procedure for isolating adenosine triphosphatase from mitochondria.", "content": "A simple method for isolation of adenosine triphosphatase (EC 3.6.1.3) from mitochondria is described. The enzyme is released from mitochondrial Lubrol particles by drastic sonication and purified by gel filtration on Sepharose 6-B. The described procedure is effective in isolating adenosine triphosphatase from rat liver as it is from beef heart mitochondria. The enzyme isolated from beef heart has a specific activity of 120 mumol P/min per mg protein and enzyme isolated from rat liver has a specific activity of 70 mumol P/min per mg protein when measured as a release of inorganic phosphate.", "contents": "A simple procedure for isolating adenosine triphosphatase from mitochondria. A simple method for isolation of adenosine triphosphatase (EC 3.6.1.3) from mitochondria is described. The enzyme is released from mitochondrial Lubrol particles by drastic sonication and purified by gel filtration on Sepharose 6-B. The described procedure is effective in isolating adenosine triphosphatase from rat liver as it is from beef heart mitochondria. The enzyme isolated from beef heart has a specific activity of 120 mumol P/min per mg protein and enzyme isolated from rat liver has a specific activity of 70 mumol P/min per mg protein when measured as a release of inorganic phosphate."}
{"id": "PMID:18171", "title": "ZETA-Potential and surface charge of Thermoplasma acidophila.", "content": "The surface charge density and the zeta-potential of Thermoplasma acidophila was estimated from microscopic electrophoresis experiments. The cells moved towards the positive electrode. The mobility remained constant from pH 2 to 5, and increased for pH values higher than 6. The mobility at pH 6 decreased dramatically with increased external Ca2+ concentration. At pH 2 and an ionic strength similar to that of the growth medium, the zeta-potential was about 8 mV, negative relative to the bulk medium; the surface charge density was 1360esu/cm-2 which corresponds to one elementary charge per 3500 A2.", "contents": "ZETA-Potential and surface charge of Thermoplasma acidophila. The surface charge density and the zeta-potential of Thermoplasma acidophila was estimated from microscopic electrophoresis experiments. The cells moved towards the positive electrode. The mobility remained constant from pH 2 to 5, and increased for pH values higher than 6. The mobility at pH 6 decreased dramatically with increased external Ca2+ concentration. At pH 2 and an ionic strength similar to that of the growth medium, the zeta-potential was about 8 mV, negative relative to the bulk medium; the surface charge density was 1360esu/cm-2 which corresponds to one elementary charge per 3500 A2."}
{"id": "PMID:18172", "title": "H/2H isotope effect in redox reactions of cytochrome c.", "content": "The rate of reaction of ferro- and ferricytochrome c (C(II) and C(III) with ferri- and ferrocyanide and of C(III) with 02- and CO2- was determined in H2O and in 2H2O in the temperature range 5-35 degrees C. No isotope effect was evident in any of the reductions of C(III); the apparent energy of activation was identical in H2O and 2H2O. An isotope effect with kH2O/k2H2O = 1.25 to 1.85, depending on pH for instance was observed in the oxidation of C(II), in the slow phase of oxidation which involves conformational changes. An interpretation (supported by evidence from previous work) involving water molecules in the close vicinity of the reaction site on the protein is discussed.", "contents": "H/2H isotope effect in redox reactions of cytochrome c. The rate of reaction of ferro- and ferricytochrome c (C(II) and C(III) with ferri- and ferrocyanide and of C(III) with 02- and CO2- was determined in H2O and in 2H2O in the temperature range 5-35 degrees C. No isotope effect was evident in any of the reductions of C(III); the apparent energy of activation was identical in H2O and 2H2O. An isotope effect with kH2O/k2H2O = 1.25 to 1.85, depending on pH for instance was observed in the oxidation of C(II), in the slow phase of oxidation which involves conformational changes. An interpretation (supported by evidence from previous work) involving water molecules in the close vicinity of the reaction site on the protein is discussed."}
{"id": "PMID:18173", "title": "CO2 reduction by intact chloroplasts under a diminished proton gradient.", "content": "9-Aminoacridine has been used to monitor the intrathylakoid pH of photosynthetically competent intact chloroplasts. Values obtained from 9-aminoacridine accumulation in the chloroplasts must be corrected for light-dependent binding of 9-aminoacridine to the thylakoid membranes. During nitrite reduction by intact chloroplasts, the intrathylakoid proton concentration increased. It decreased somewhat during CO2 reduction. However, low concentrations of uncoupling amines such as NH3 or cyclohexylamine, which rapidly penetrated the chloroplast envelope and decreased the intrathylakoid proton concentration, failed to reduce, and actually stimulated, rates of CO2-dependent oxygen evolution even under rate-limiting light. In contrast, low concentrations of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) OR NIGERICIN, WHICH INHIBITED CO2 reduction, even appeared to increase the intrathylakoid proton concentration. As indicated by measurements of the 515 nm signal of the chloroplasts, the light-induced membrane potential was not much affected by low concentrations of the uncoupling amines, but was decreased by FCCP and by high concentrations of the amines. Even in the presence of high concentrations of NH4C1, ATP/ADP ratios of illuminated chloroplasts remained far above the ratios observed in the dark. In contrast, low concentrations of FCCP were sufficient to reduce ATP/ADP ratios to the dark value even under high intensity illumination. The observations are difficult to explain within the framework of the chemiosmotic hypothesis as presently discussed.", "contents": "CO2 reduction by intact chloroplasts under a diminished proton gradient. 9-Aminoacridine has been used to monitor the intrathylakoid pH of photosynthetically competent intact chloroplasts. Values obtained from 9-aminoacridine accumulation in the chloroplasts must be corrected for light-dependent binding of 9-aminoacridine to the thylakoid membranes. During nitrite reduction by intact chloroplasts, the intrathylakoid proton concentration increased. It decreased somewhat during CO2 reduction. However, low concentrations of uncoupling amines such as NH3 or cyclohexylamine, which rapidly penetrated the chloroplast envelope and decreased the intrathylakoid proton concentration, failed to reduce, and actually stimulated, rates of CO2-dependent oxygen evolution even under rate-limiting light. In contrast, low concentrations of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) OR NIGERICIN, WHICH INHIBITED CO2 reduction, even appeared to increase the intrathylakoid proton concentration. As indicated by measurements of the 515 nm signal of the chloroplasts, the light-induced membrane potential was not much affected by low concentrations of the uncoupling amines, but was decreased by FCCP and by high concentrations of the amines. Even in the presence of high concentrations of NH4C1, ATP/ADP ratios of illuminated chloroplasts remained far above the ratios observed in the dark. In contrast, low concentrations of FCCP were sufficient to reduce ATP/ADP ratios to the dark value even under high intensity illumination. The observations are difficult to explain within the framework of the chemiosmotic hypothesis as presently discussed."}
{"id": "PMID:18174", "title": "The effect of chloroplast coupling factor removal on thylakoid membrane ion permeability.", "content": "Removal of coupling factor protein (CF1) from spinach thylakoid membranes results in an enhancement of proton permeability but has no effect on chloride or potassium permeability. Anion permeability was measured by the rate of thylakoid packed volume changes. Potassium permeability was monitored by turbidity changes, packed thylakoid volume changes and ion flux studies using 86Rb+ as a tracer. 45Ca2+ was used to measure divalent cation fluxes. CF1-depleted chloroplasts had an unaltered rate of Ca2+ uptake, but the rate of Ca2+ efflux appeared to be increased. Calcium efflux rates could also be increased by the addition of a proton specific uncoupler, FCCP.", "contents": "The effect of chloroplast coupling factor removal on thylakoid membrane ion permeability. Removal of coupling factor protein (CF1) from spinach thylakoid membranes results in an enhancement of proton permeability but has no effect on chloride or potassium permeability. Anion permeability was measured by the rate of thylakoid packed volume changes. Potassium permeability was monitored by turbidity changes, packed thylakoid volume changes and ion flux studies using 86Rb+ as a tracer. 45Ca2+ was used to measure divalent cation fluxes. CF1-depleted chloroplasts had an unaltered rate of Ca2+ uptake, but the rate of Ca2+ efflux appeared to be increased. Calcium efflux rates could also be increased by the addition of a proton specific uncoupler, FCCP."}
{"id": "PMID:18175", "title": "Identification of S2 as the sensitive state to alkaline photoinactivation of photosystem II in chloroplasts.", "content": "1. Chloroplasts have been preilluminated by a sequence of n short saturating flashes immediately before alkalinization to pH 9.3, and brought back 2 min later to pH 7.8. The assay of Photosystem II activity through dichlorophenolindophenol photoreduction, oxygen evolution, fluorescence induction, shows that part of the centers is inactivated and that this part depends on the number of preilluminating flashes (maximum inhibition after one flash) in a way which suggests identification of state S2 as the target for alkaline inactivation. 2. As shown by Reimer and Trebst ((1975) Biochem. Physiol. Pflanz. 168, 225-232) the inactivation necessitates the presence of gramicidin, which shows that the sensitive site is on the internal side of the thylakoid membrane. 3. The electron flow through inactivated Photosystem II is restored by artificial donor addition (diphenylcarbazide or hydroxylamine); this suggests that the water-splitting enzyme itself is blocked. The inactivation is accompanied by a solubilization of bound Mn2+ and by the occurence of EPR Signal II \"fast\". 4. Glutaraldehyde fixation before the treatment does not prevent the inactivation which thus does not seem to involve a protein structural change.", "contents": "Identification of S2 as the sensitive state to alkaline photoinactivation of photosystem II in chloroplasts. 1. Chloroplasts have been preilluminated by a sequence of n short saturating flashes immediately before alkalinization to pH 9.3, and brought back 2 min later to pH 7.8. The assay of Photosystem II activity through dichlorophenolindophenol photoreduction, oxygen evolution, fluorescence induction, shows that part of the centers is inactivated and that this part depends on the number of preilluminating flashes (maximum inhibition after one flash) in a way which suggests identification of state S2 as the target for alkaline inactivation. 2. As shown by Reimer and Trebst ((1975) Biochem. Physiol. Pflanz. 168, 225-232) the inactivation necessitates the presence of gramicidin, which shows that the sensitive site is on the internal side of the thylakoid membrane. 3. The electron flow through inactivated Photosystem II is restored by artificial donor addition (diphenylcarbazide or hydroxylamine); this suggests that the water-splitting enzyme itself is blocked. The inactivation is accompanied by a solubilization of bound Mn2+ and by the occurence of EPR Signal II \"fast\". 4. Glutaraldehyde fixation before the treatment does not prevent the inactivation which thus does not seem to involve a protein structural change."}
{"id": "PMID:18177", "title": "A Cl-/HCO-3-ATPase in the gills of Carassius auratus. Its inhibition by thiocyanate.", "content": "An ATPase is demonstrated in plasma membrane fractions of goldfish gills. This enzyme is stimulated by Cl- and HCO-3, inhibited by SCN-. Biochemical characterization shows that HCO-3 stimulation (Km = 2.5 mequiv./l) is specifically inhibited in a competitive fashion by SCN- (Ki = 0.25 mequiv./l). This residual Mg2+-dependent activity is weakly affected by SCN-. In the microsomal fraction chloride stimulation of the enzyme occurs in the presence of HCO-3 (Km for chloride = 1 mequiv/l); no stimulation is observed in the absence of HCO-3. Thiocyanate exhibits a mixed type of inhibition (Ki = 0.06 mequiv./l) towards the Cl- stimulation of the enzyme. Bicarbonate-dependent ATPase from the mitochondrial fraction is stimulated by Cl-, but this enzyme has a relatively weak affinity for this substrate (Km = 14 mequiv./l).", "contents": "A Cl-/HCO-3-ATPase in the gills of Carassius auratus. Its inhibition by thiocyanate. An ATPase is demonstrated in plasma membrane fractions of goldfish gills. This enzyme is stimulated by Cl- and HCO-3, inhibited by SCN-. Biochemical characterization shows that HCO-3 stimulation (Km = 2.5 mequiv./l) is specifically inhibited in a competitive fashion by SCN- (Ki = 0.25 mequiv./l). This residual Mg2+-dependent activity is weakly affected by SCN-. In the microsomal fraction chloride stimulation of the enzyme occurs in the presence of HCO-3 (Km for chloride = 1 mequiv/l); no stimulation is observed in the absence of HCO-3. Thiocyanate exhibits a mixed type of inhibition (Ki = 0.06 mequiv./l) towards the Cl- stimulation of the enzyme. Bicarbonate-dependent ATPase from the mitochondrial fraction is stimulated by Cl-, but this enzyme has a relatively weak affinity for this substrate (Km = 14 mequiv./l)."}
{"id": "PMID:18179", "title": "Proton-induced uptake of mammalian DNA by dog erythrocyte pink ghosts.", "content": "Low pH (below 6) induces the uptake of mammalian DNA in dog erythrocyte pink ghosts. Uptake requires either Ca2+ or Mg2+ and is stimulated by ATP. These agents induce a rapid sphering of the ghosts at 37 degrees C and sphering is required for uptake. Uptake is increased in ghosts which have been incubated 60-90 min before adding the DNA. Uptake is strongly temperature-dependent. Lowering the temperature of a suspension of ghosts taking up DNA at 37-0 degrees C stops uptake. It is concluded that uptake depends on active membrane processes and that it may depend on the capacity of the ghosts to maintain cation exchange.", "contents": "Proton-induced uptake of mammalian DNA by dog erythrocyte pink ghosts. Low pH (below 6) induces the uptake of mammalian DNA in dog erythrocyte pink ghosts. Uptake requires either Ca2+ or Mg2+ and is stimulated by ATP. These agents induce a rapid sphering of the ghosts at 37 degrees C and sphering is required for uptake. Uptake is increased in ghosts which have been incubated 60-90 min before adding the DNA. Uptake is strongly temperature-dependent. Lowering the temperature of a suspension of ghosts taking up DNA at 37-0 degrees C stops uptake. It is concluded that uptake depends on active membrane processes and that it may depend on the capacity of the ghosts to maintain cation exchange."}
{"id": "PMID:18180", "title": "Regulatory effects of purine nucleotide analogs with liver glutamate dehydrogenase.", "content": "A total of 26 different purine nucleotides with specific modifications in the base moiety and/or in the polyphosphate chain as well as various combinations of nucleotides were tested as allosteric effectors of beef liver glutamate dehydrogenase (L-glutamate : NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3). The capacity of these nucleotide analogs to activate or to inhibit the glutamate dehydrogenase activity is expressed quantitatively and scaled between the extreme effects of ADP and GTP, respectively. The significance of distinct structural elements for the enzyme-effector interaction is discussed. While the inhibitory GTP site is less specific, accepting many natural and most modified nucleoside triphosphates as inhibitors, the activating ADP site shows a much higher specificity for nucleotides as activators.", "contents": "Regulatory effects of purine nucleotide analogs with liver glutamate dehydrogenase. A total of 26 different purine nucleotides with specific modifications in the base moiety and/or in the polyphosphate chain as well as various combinations of nucleotides were tested as allosteric effectors of beef liver glutamate dehydrogenase (L-glutamate : NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3). The capacity of these nucleotide analogs to activate or to inhibit the glutamate dehydrogenase activity is expressed quantitatively and scaled between the extreme effects of ADP and GTP, respectively. The significance of distinct structural elements for the enzyme-effector interaction is discussed. While the inhibitory GTP site is less specific, accepting many natural and most modified nucleoside triphosphates as inhibitors, the activating ADP site shows a much higher specificity for nucleotides as activators."}
{"id": "PMID:18181", "title": "Reduction of oxidised folates by dihydrofolate reductase from methotrexate-resistant Lactobacillus casei.", "content": "The use of alternative substrates by dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) was investigated as a possible mechanism for the resistance of Lactobacillus casei to the cytotoxic drug methotrexate. The reduction of folic acid and 10-formylfolic acid by homogeneous enzyme was compared to that of the normal substrate, dihydrofolic acid. The three substrates have different pH optima and Km values. In addition, it was found that the reduction of 10-formylfolic acid was markedly stimulated by the presence of ions. Although the reduction was sensitive to methotrexate in all cases, the ion activation may be of importance in partially inhibited systems.", "contents": "Reduction of oxidised folates by dihydrofolate reductase from methotrexate-resistant Lactobacillus casei. The use of alternative substrates by dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) was investigated as a possible mechanism for the resistance of Lactobacillus casei to the cytotoxic drug methotrexate. The reduction of folic acid and 10-formylfolic acid by homogeneous enzyme was compared to that of the normal substrate, dihydrofolic acid. The three substrates have different pH optima and Km values. In addition, it was found that the reduction of 10-formylfolic acid was markedly stimulated by the presence of ions. Although the reduction was sensitive to methotrexate in all cases, the ion activation may be of importance in partially inhibited systems."}
{"id": "PMID:18182", "title": "Purification and properties of the NAD(P)H:nitrate reductase of the yeast Rhodotorula glutinis.", "content": "The assimilatory nitrate reductase from the yeast Rhodotorula glutinus has been purified 740-fold, its different catalytic activities have been characterized and some inhibitors studied. The purified enzyme (150 units per mg protein) contains a cytochrome of the b-557 type. An S20,w of 7.9 S was found by the use of sucrose density gradient centrifugation, and a Stokes radius of 7.05 nm was determined by gel filtration. From these values, a molecular weight of 230 000 was estimated for the native enzyme. The purified preparation consisted of two electrophoretically distinguishable proteins, both of which exhibited nitrate reductase activity. The species with the higher electrophoretic mobility which represented the great majority of the total nitrate reductase gave a positive stain for heme and was shown to be composed of subunits with a molecular weight of about 118 000. Thus the molecule contains two subunits of the same size.", "contents": "Purification and properties of the NAD(P)H:nitrate reductase of the yeast Rhodotorula glutinis. The assimilatory nitrate reductase from the yeast Rhodotorula glutinus has been purified 740-fold, its different catalytic activities have been characterized and some inhibitors studied. The purified enzyme (150 units per mg protein) contains a cytochrome of the b-557 type. An S20,w of 7.9 S was found by the use of sucrose density gradient centrifugation, and a Stokes radius of 7.05 nm was determined by gel filtration. From these values, a molecular weight of 230 000 was estimated for the native enzyme. The purified preparation consisted of two electrophoretically distinguishable proteins, both of which exhibited nitrate reductase activity. The species with the higher electrophoretic mobility which represented the great majority of the total nitrate reductase gave a positive stain for heme and was shown to be composed of subunits with a molecular weight of about 118 000. Thus the molecule contains two subunits of the same size."}
{"id": "PMID:18183", "title": "On the determination of isozyme levels in preparations containing cytoplasmic and mitochondrial aspartate aminotransferase.", "content": "A spectrophotometric assay has been developed for the determination of the content of each isozyme of aspartate transaminase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) in physiological fluids or tissue extracts. The methods relies on the ability of adipate, at low pH and ionic strength to inhibit the cytoplasmic isozyme but not the one from mitochondria. Two assays are necessary, one at pH 8.0 which measures the content of both isozymes and another at low pH which measures primarily the amount of mitochondrial isozyme. Results obtained by this simple procedure match those in which each isozyme is inhibited by its antibody. The validity of the results obtained by the new method was tested at different ratios of cytoplasmic:mitochondrial isozyme and with tissue extracts. Since the amounts of each isozyme determined by radial immunodiffusion match those values gathered by following enzymatic activity, it is concluded that the quantity of each isozyme obtained from its respective catalytic activity must represent the total protein content of each isozyme in a given sample.", "contents": "On the determination of isozyme levels in preparations containing cytoplasmic and mitochondrial aspartate aminotransferase. A spectrophotometric assay has been developed for the determination of the content of each isozyme of aspartate transaminase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) in physiological fluids or tissue extracts. The methods relies on the ability of adipate, at low pH and ionic strength to inhibit the cytoplasmic isozyme but not the one from mitochondria. Two assays are necessary, one at pH 8.0 which measures the content of both isozymes and another at low pH which measures primarily the amount of mitochondrial isozyme. Results obtained by this simple procedure match those in which each isozyme is inhibited by its antibody. The validity of the results obtained by the new method was tested at different ratios of cytoplasmic:mitochondrial isozyme and with tissue extracts. Since the amounts of each isozyme determined by radial immunodiffusion match those values gathered by following enzymatic activity, it is concluded that the quantity of each isozyme obtained from its respective catalytic activity must represent the total protein content of each isozyme in a given sample."}
{"id": "PMID:18184", "title": "Protein kinases of rabbit and human erythrocyte membranes. Solubilization and characterization.", "content": "Two protein kinases (EC 2.7.1.37) from rabbit and one from human erythrocyte membranes have been solubilized with 0.5 M NaCl. These enzymes have been partially purified by (NH4)2SO4 fractionation and gel filtration. The rabbit membrane enzymes have apparent Mr values of 100 000 and 30 000, as determined in the presence of 0.4 M NaCl. In the absence of salt, these enzymes aggregate into high molecular weight species. The kinase from human erythrocyte membranes has an apparent Mr of 30 000 and appears to have properties similar to those of the 30 000-dalton rabbit kinase. All three enzymes catalyze the phosphorylation of casein and phosvitin in salt-stimulated reactions. None of these enzymes appears to be related to cyclic AMP-dependent protein kinases.", "contents": "Protein kinases of rabbit and human erythrocyte membranes. Solubilization and characterization. Two protein kinases (EC 2.7.1.37) from rabbit and one from human erythrocyte membranes have been solubilized with 0.5 M NaCl. These enzymes have been partially purified by (NH4)2SO4 fractionation and gel filtration. The rabbit membrane enzymes have apparent Mr values of 100 000 and 30 000, as determined in the presence of 0.4 M NaCl. In the absence of salt, these enzymes aggregate into high molecular weight species. The kinase from human erythrocyte membranes has an apparent Mr of 30 000 and appears to have properties similar to those of the 30 000-dalton rabbit kinase. All three enzymes catalyze the phosphorylation of casein and phosvitin in salt-stimulated reactions. None of these enzymes appears to be related to cyclic AMP-dependent protein kinases."}
{"id": "PMID:18185", "title": "The influence of changes in the phospholipid pattern of intact fibroblasts on the activities of four membrane-bound enzymes.", "content": "Human skin fibroblasts, grown to confluency in the presence of 32P for random labelling of the phospholipids, showed upon 24 h incubation in the presence of either 8 mM L-serine or 4 mM ethanolamine an increased content of phosphatidylserine (150% of control cells) or phosphatidylethanolamine (116% of control cells), respectively. Concomitantly the phosphatidylcholine correspondingly decreased. Upon cell harvesting and gentle enzyme preparation the base-treated cells demonstrated a significantly higher unstimulated, fluoride- and thyrotropin-stimulated activity of adenylate cyclase. The activities of total ATPase, ouabain-sensitive ATPase, 5'-nucleotidase and gamma-glutamyltransferase remained unaltered. When subjecting enzyme preparations from fibroblasts to ultrasonication the activity of adenylate cyclase decreased progressively with energy applied, whereas the activities of the other enzymes were unaltered ((K+ + Na+)-ATPase, 5'-nucleotidase) or even increased (Mg2+-ATPase, gamma-glutamyltransferase). The results have a bearing upon the regulatory function of the phospholipid microenvironment of membrane-bound enzymes.", "contents": "The influence of changes in the phospholipid pattern of intact fibroblasts on the activities of four membrane-bound enzymes. Human skin fibroblasts, grown to confluency in the presence of 32P for random labelling of the phospholipids, showed upon 24 h incubation in the presence of either 8 mM L-serine or 4 mM ethanolamine an increased content of phosphatidylserine (150% of control cells) or phosphatidylethanolamine (116% of control cells), respectively. Concomitantly the phosphatidylcholine correspondingly decreased. Upon cell harvesting and gentle enzyme preparation the base-treated cells demonstrated a significantly higher unstimulated, fluoride- and thyrotropin-stimulated activity of adenylate cyclase. The activities of total ATPase, ouabain-sensitive ATPase, 5'-nucleotidase and gamma-glutamyltransferase remained unaltered. When subjecting enzyme preparations from fibroblasts to ultrasonication the activity of adenylate cyclase decreased progressively with energy applied, whereas the activities of the other enzymes were unaltered ((K+ + Na+)-ATPase, 5'-nucleotidase) or even increased (Mg2+-ATPase, gamma-glutamyltransferase). The results have a bearing upon the regulatory function of the phospholipid microenvironment of membrane-bound enzymes."}
{"id": "PMID:18186", "title": "Biochemical characterization of alkaline phosphatase in guinea pig thymus.", "content": "1. Alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1) in guinea pig thymus was extracted optimally in 10 mM Tris - HCl buffer at pH 8.0 containing 5 g/l Triton X-100. 2. alpha-Glycerophosphate, beta-glycerophosphate and phenolphthalein monophosphate were hydrolyzed by thymus extract with a pH optimum at 9.8-10.0, whereas p-nitrophenylphosphate and alpha-naphthylphosphate were hydrolyzed with pH optima at 10.7-10.8 and beta-naphthylphosphate at pH 11.2. P-Nitrophenylphosphate and phenolphthalein monophosphate proved to be the most suitable substrates. 3. Alkaline phosphatase was effectively inhibited by EDTA, Zn2+, histidine and urea therefore resembling the inhibition characteristics of alkaline phosphatase in the placenta and kidney, but not that in the liver and intestine, which differed markedly. 4. DEAE-cellulose chromatography and polyacrylamide disc electrophoresis revealed three enzyme peaks which did not differ in their substrate specificities and modifier characteristics. 5. Polyacrylamide disc electrophoresis of thymus, serum, placenta, kidney, liver, bone and intestine revealed no alkaline phosphatase bands definitely unique to thymus.", "contents": "Biochemical characterization of alkaline phosphatase in guinea pig thymus. 1. Alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1) in guinea pig thymus was extracted optimally in 10 mM Tris - HCl buffer at pH 8.0 containing 5 g/l Triton X-100. 2. alpha-Glycerophosphate, beta-glycerophosphate and phenolphthalein monophosphate were hydrolyzed by thymus extract with a pH optimum at 9.8-10.0, whereas p-nitrophenylphosphate and alpha-naphthylphosphate were hydrolyzed with pH optima at 10.7-10.8 and beta-naphthylphosphate at pH 11.2. P-Nitrophenylphosphate and phenolphthalein monophosphate proved to be the most suitable substrates. 3. Alkaline phosphatase was effectively inhibited by EDTA, Zn2+, histidine and urea therefore resembling the inhibition characteristics of alkaline phosphatase in the placenta and kidney, but not that in the liver and intestine, which differed markedly. 4. DEAE-cellulose chromatography and polyacrylamide disc electrophoresis revealed three enzyme peaks which did not differ in their substrate specificities and modifier characteristics. 5. Polyacrylamide disc electrophoresis of thymus, serum, placenta, kidney, liver, bone and intestine revealed no alkaline phosphatase bands definitely unique to thymus."}
{"id": "PMID:18191", "title": "Histidine and lysine residues and the activity of phospholipase A2 from the venom of Bitis gabonica.", "content": "Chemical modification of phospholipase A2 (phosphatide 2-acyl-hydrolase, EC 3.1.1.4) from the venom of gaboon adder (Bitis gabonica) showed that histidine and lysine residues are essential for enzyme activity. Treatment with p-bromophenacyl bromide or pyridoxal 5'-phosphate resulted in the specific covalent modification of one histidine or a total of one lysine residue per molecule of enzyme, respectively, with a concomitant loss of enzyme activity. Competitive protection against modification and inactivation was afforded by the presence of Ca2+ and/or micellar concentrations of substrate analogue, lysophosphatidylcholine. Neither modification caused any significant conformational change, as judged from circular dichroic properties. Amino acid analyses and the alignment of peptides from cyanogen bromide and proteolytic cleavage of modified enzyme preparations delineated His-45 as the only residue modified by p-bromophenacyl bromide. However, pyridoxal 5'-phosphate was shown to have reacted not with a single lysine but with four different ones (residues 11, 33, 58 and 111) in such a manner that an overall stoichiometry of one modified lysine residue/molecule enzyme resulted. Apparently, the essential function of lysine could be fulfilled by any one out of these four residues.", "contents": "Histidine and lysine residues and the activity of phospholipase A2 from the venom of Bitis gabonica. Chemical modification of phospholipase A2 (phosphatide 2-acyl-hydrolase, EC 3.1.1.4) from the venom of gaboon adder (Bitis gabonica) showed that histidine and lysine residues are essential for enzyme activity. Treatment with p-bromophenacyl bromide or pyridoxal 5'-phosphate resulted in the specific covalent modification of one histidine or a total of one lysine residue per molecule of enzyme, respectively, with a concomitant loss of enzyme activity. Competitive protection against modification and inactivation was afforded by the presence of Ca2+ and/or micellar concentrations of substrate analogue, lysophosphatidylcholine. Neither modification caused any significant conformational change, as judged from circular dichroic properties. Amino acid analyses and the alignment of peptides from cyanogen bromide and proteolytic cleavage of modified enzyme preparations delineated His-45 as the only residue modified by p-bromophenacyl bromide. However, pyridoxal 5'-phosphate was shown to have reacted not with a single lysine but with four different ones (residues 11, 33, 58 and 111) in such a manner that an overall stoichiometry of one modified lysine residue/molecule enzyme resulted. Apparently, the essential function of lysine could be fulfilled by any one out of these four residues."}
{"id": "PMID:18193", "title": "Intrinsic catalytic activity of procarboxypeptidase A. A kinetic study using fluorine analogues.", "content": "Bovine procarboxypeptidase A displays substantial catalytic activity toward halogenated acyl-amino acids, the most active of which is trifluoroacetyl-L-phenylalanine (TFAc-L-Phe). Though this activity is not as great as for the native enzyme, it is quite substantial and far beyond the range of adventitious activation. Both DL-benzylcuccinate and beta-phenylpropionate inhibit zymogen hydrolysis of TFAc-L-Phe, the former with a K1 of 4.1 micrometer and the latter, 900 micrometer (a value much higher than the corresponding enzyme). Apo procarboxypeptidase A will also hydrolyze TFAc-L-Phe, presumably the polarization of the carbonyl carbon being accomplished by the fluorine atoms in the absence of a specific metal ion. That this is not entirely the metal ion function is indicated by the fact that rate enhancements follow the order manganese procarboxypeptidase A approximately zinc procarboxypeptidase greater than apo-procarboxypeptidase. The results indicate considerable similarities for the zymogen-enzyme pair in terms of catalytic groups, pH dependence, specificity and the nature of their transition state binding sites. Some changes in the substrate or inhibitor binding sites are noted.", "contents": "Intrinsic catalytic activity of procarboxypeptidase A. A kinetic study using fluorine analogues. Bovine procarboxypeptidase A displays substantial catalytic activity toward halogenated acyl-amino acids, the most active of which is trifluoroacetyl-L-phenylalanine (TFAc-L-Phe). Though this activity is not as great as for the native enzyme, it is quite substantial and far beyond the range of adventitious activation. Both DL-benzylcuccinate and beta-phenylpropionate inhibit zymogen hydrolysis of TFAc-L-Phe, the former with a K1 of 4.1 micrometer and the latter, 900 micrometer (a value much higher than the corresponding enzyme). Apo procarboxypeptidase A will also hydrolyze TFAc-L-Phe, presumably the polarization of the carbonyl carbon being accomplished by the fluorine atoms in the absence of a specific metal ion. That this is not entirely the metal ion function is indicated by the fact that rate enhancements follow the order manganese procarboxypeptidase A approximately zinc procarboxypeptidase greater than apo-procarboxypeptidase. The results indicate considerable similarities for the zymogen-enzyme pair in terms of catalytic groups, pH dependence, specificity and the nature of their transition state binding sites. Some changes in the substrate or inhibitor binding sites are noted."}
{"id": "PMID:18194", "title": "Studies on (Na+ +K+) activated ATPase. XLI. Effects of N-ethylmaleimide on overall and partial reactions.", "content": "1. Preincubation with N-ethylmaleimide inhibits the overall activity of highly purified (Na+ +K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations of rabbit kidney outer medulla. 2. This inhibition is decreased by addition of ATP or 4-nitrophenylphosphate under non-phosphorylating conditions, and also by addition of ADP or adenylylimidodiphosphate. 3. N-ethylmaleimide treatment leads to inhibition of K+-stimulated 4-nitrophenylphosphatase activity, Na+-stimulated ATPase activity, and phosphorylation by ATP as well as by inorganic phosphate. These inhibitions strictly parallel that of the overal (Na+ +K+)-ATPase reaction. 4. N-ethylmaleimide lowers the number of sites which are phosphorylated by inorganic phosphate, without affecting the dissociation constant of the enzyme-phosphate complex. 5. N-ethylmaleimide does not affect the relative stimulation by ATP of the K+-stimulated 4-nitrophenylphosphatase activity. 6. These effects of N-ethylmaleimide can be explained as a complete loss of active enzyme, either by reaction of N-ethylmaleimide inside the active center, or by alterations in the quaternary structure through reactions outside the active center.", "contents": "Studies on (Na+ +K+) activated ATPase. XLI. Effects of N-ethylmaleimide on overall and partial reactions. 1. Preincubation with N-ethylmaleimide inhibits the overall activity of highly purified (Na+ +K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations of rabbit kidney outer medulla. 2. This inhibition is decreased by addition of ATP or 4-nitrophenylphosphate under non-phosphorylating conditions, and also by addition of ADP or adenylylimidodiphosphate. 3. N-ethylmaleimide treatment leads to inhibition of K+-stimulated 4-nitrophenylphosphatase activity, Na+-stimulated ATPase activity, and phosphorylation by ATP as well as by inorganic phosphate. These inhibitions strictly parallel that of the overal (Na+ +K+)-ATPase reaction. 4. N-ethylmaleimide lowers the number of sites which are phosphorylated by inorganic phosphate, without affecting the dissociation constant of the enzyme-phosphate complex. 5. N-ethylmaleimide does not affect the relative stimulation by ATP of the K+-stimulated 4-nitrophenylphosphatase activity. 6. These effects of N-ethylmaleimide can be explained as a complete loss of active enzyme, either by reaction of N-ethylmaleimide inside the active center, or by alterations in the quaternary structure through reactions outside the active center."}
{"id": "PMID:18195", "title": "Concerted inhibition of NADP+-specific isocitrate dehydrogenase by oxalacetate and glyoxylate. I. Oxalomalate formation and stability, and nature of the enzyme inhibition.", "content": "Oxalacetate and glyoxylate are each weak inhibitors of NADP+-specific isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42)9 Together, however, they act in a concerted manner and strongly inhibit the enzyme. The rates of formation and dissociation of the enzyme inhibitor complex, and the rate of formation and the stability of the aldol condensation product of oxalacetate and glyoxylate, oxalomalate, were examined. The data obtained do not support the often suggested possibility that oxalomalate, per se, formed non-enzymatically in isocitrate dehydrogenase assay mixtures containing oxalacetate and glyoxylate, is responsible for the observed inhibition of the enzyme. Rather, the data presented in this communication suggest that oxalacetate binds to the enzyme first, and that the subsequent binding of glyoxylate leads to the formation of a catalytically inactive enzyme-inhibitor complex.", "contents": "Concerted inhibition of NADP+-specific isocitrate dehydrogenase by oxalacetate and glyoxylate. I. Oxalomalate formation and stability, and nature of the enzyme inhibition. Oxalacetate and glyoxylate are each weak inhibitors of NADP+-specific isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42)9 Together, however, they act in a concerted manner and strongly inhibit the enzyme. The rates of formation and dissociation of the enzyme inhibitor complex, and the rate of formation and the stability of the aldol condensation product of oxalacetate and glyoxylate, oxalomalate, were examined. The data obtained do not support the often suggested possibility that oxalomalate, per se, formed non-enzymatically in isocitrate dehydrogenase assay mixtures containing oxalacetate and glyoxylate, is responsible for the observed inhibition of the enzyme. Rather, the data presented in this communication suggest that oxalacetate binds to the enzyme first, and that the subsequent binding of glyoxylate leads to the formation of a catalytically inactive enzyme-inhibitor complex."}
{"id": "PMID:18196", "title": "Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes.", "content": "Human liver extracts show two major bands with aldehyde dehydrogenase (Aldehyde:NAD+ oxidoreductase, EC 1.2.1.3) activity via starch gel electrophoresis at pH 7.0. Both bands have been purified to apparent homogeneity via classical chromatography combined with affinity chromatography on 5'-AMP-Sepharose 4B. The slower migrating band, enzyme 1, when assayed at pH 9.5 has a low Km for NAD (8 micrometer) and a high Km for acetaldehyde (approx. 0.1 mM). It is very strongly inhibited by disulfiram at pH 7.0 with a Ki of 0.2 micrometer. The faster migrating band, enzyme 2, has a low Km for acetaldehyde, (2--3 micrometer at pH 9.5), a higher Km for NAD (70 micrometer at pH 9.5), and is not inhibited by disulfiram at pH 7.0. The two enzymes are very similar to the F1 and F2 isozymes of horse liver purified by Eckfeldt et al. (Eckfeldt, J., Mope, L., Takio, K. and Yonetani, T. (1976) J. Biol, Chem. 251, 236-240) in molecular weight, subunit composition, amino acid composition and extinction coefficient. Preliminary kinetic characterizations of the enzyme are presented.", "contents": "Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Human liver extracts show two major bands with aldehyde dehydrogenase (Aldehyde:NAD+ oxidoreductase, EC 1.2.1.3) activity via starch gel electrophoresis at pH 7.0. Both bands have been purified to apparent homogeneity via classical chromatography combined with affinity chromatography on 5'-AMP-Sepharose 4B. The slower migrating band, enzyme 1, when assayed at pH 9.5 has a low Km for NAD (8 micrometer) and a high Km for acetaldehyde (approx. 0.1 mM). It is very strongly inhibited by disulfiram at pH 7.0 with a Ki of 0.2 micrometer. The faster migrating band, enzyme 2, has a low Km for acetaldehyde, (2--3 micrometer at pH 9.5), a higher Km for NAD (70 micrometer at pH 9.5), and is not inhibited by disulfiram at pH 7.0. The two enzymes are very similar to the F1 and F2 isozymes of horse liver purified by Eckfeldt et al. (Eckfeldt, J., Mope, L., Takio, K. and Yonetani, T. (1976) J. Biol, Chem. 251, 236-240) in molecular weight, subunit composition, amino acid composition and extinction coefficient. Preliminary kinetic characterizations of the enzyme are presented."}
{"id": "PMID:18197", "title": "Purification and some properties of gamma-glutamyltransferase from human liver.", "content": "The purification of gamma-glutamyltransferase ((gamma-glutamyl)-peptide: amino acid gamma-glutamyltransferase, EC 2.3.2.2) from normal human liver is described. The procedure includes solubilization of enzyme from membranes using deoxycholate and Lubrol W, treatment with acetone and butanol, and affinity chromatography on immobilized concanavalin A. Treatment with papain was used to release the enzyme from aggregates of lipid and protein, prior to further purification. On overall purification of 9400 was achieved and analytical polyacrylamide gel electrophoresis indicated that the final product was homogeneous, and had a molecular weight of 110 000. Two subunits were identified on dodecyl sulfate gel electrophoresis with estimated molecular weights of 47 000 and 22 000. The kinetic properties studied for the purified enzyme were similar to those found for partially purified (not papain-treated) enzyme, and resembled those of serum gamma-glutamyltransferase. The true KM values for the liver enzyme were estimated to 0.81 mM for gamma-glutamyl-p-nitroanilide and to 12.4 mM for glycyl-glycine.", "contents": "Purification and some properties of gamma-glutamyltransferase from human liver. The purification of gamma-glutamyltransferase ((gamma-glutamyl)-peptide: amino acid gamma-glutamyltransferase, EC 2.3.2.2) from normal human liver is described. The procedure includes solubilization of enzyme from membranes using deoxycholate and Lubrol W, treatment with acetone and butanol, and affinity chromatography on immobilized concanavalin A. Treatment with papain was used to release the enzyme from aggregates of lipid and protein, prior to further purification. On overall purification of 9400 was achieved and analytical polyacrylamide gel electrophoresis indicated that the final product was homogeneous, and had a molecular weight of 110 000. Two subunits were identified on dodecyl sulfate gel electrophoresis with estimated molecular weights of 47 000 and 22 000. The kinetic properties studied for the purified enzyme were similar to those found for partially purified (not papain-treated) enzyme, and resembled those of serum gamma-glutamyltransferase. The true KM values for the liver enzyme were estimated to 0.81 mM for gamma-glutamyl-p-nitroanilide and to 12.4 mM for glycyl-glycine."}
{"id": "PMID:18198", "title": "Partial purification and some properties of gamma-glutamyl transpeptidase from human bile.", "content": "1. Gamma-Glutamyl transpepetidase ((5-glutamyl)-peptide: amino acid 5-glutamyltransferase, EC 2.3.2.2) from human bile has been partially purified using protamine sulphate treatment, DEAE-cellulose chromatography and Sephadex G-200 filtration. The procedure resulted in 150-fold increase in specific acitivity with a 37% yield. 2. The partially purified enzyme showed a single zone of enzyme activity by polyacrylamide gel electrophoresis and eluted in the inner volume of Sephadex G-200. 3. The enzyme had a pH optimum of 8.1 and Km of 1.52 mM using gamma-glutamyl p-nitroanilide as substrate. 4. The effects of cations and different gamma-glutamyl acceptors on the activity of the enzyme are reported. 5. As bile gamma-glutamyl transpeptidase appears to be soluble in the absence of detergents, it is suggested that bile may prove to be a useful source for further studies of the kinetic properties and physiological role of human gamma-glutamyl transpeptidase.", "contents": "Partial purification and some properties of gamma-glutamyl transpeptidase from human bile. 1. Gamma-Glutamyl transpepetidase ((5-glutamyl)-peptide: amino acid 5-glutamyltransferase, EC 2.3.2.2) from human bile has been partially purified using protamine sulphate treatment, DEAE-cellulose chromatography and Sephadex G-200 filtration. The procedure resulted in 150-fold increase in specific acitivity with a 37% yield. 2. The partially purified enzyme showed a single zone of enzyme activity by polyacrylamide gel electrophoresis and eluted in the inner volume of Sephadex G-200. 3. The enzyme had a pH optimum of 8.1 and Km of 1.52 mM using gamma-glutamyl p-nitroanilide as substrate. 4. The effects of cations and different gamma-glutamyl acceptors on the activity of the enzyme are reported. 5. As bile gamma-glutamyl transpeptidase appears to be soluble in the absence of detergents, it is suggested that bile may prove to be a useful source for further studies of the kinetic properties and physiological role of human gamma-glutamyl transpeptidase."}
{"id": "PMID:18199", "title": "Reversible modification of amino groups in aspartate aminotransferase.", "content": "Amino  groups in the pyridoxal phosphate, pyridoxamine phosphate, and apo forms of pig heart cytoplasmic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC .2.6.1.1) have been reversibly modified with 2,4-pentanedione. The rate of modification has been measured spectrophotometrically by observing the formation of the enamine produced and this rate has been compared with the rate of loss of catalytic activity for all three forms of the enzyme. Of the 21 amino groups per 46 500 molecular weight, approx. 16 can be modified in the pyridoxal phosphate form with less than a 50% change in the catalytic activity of the enzyme. A slow inactivation occurs which is probably due to reaction of 2,4-pentanedione with the enzyme-bound pyridoxal phosphate. The pyridoxamine phosphate enzyme is completely inactivated by reaction with 2,4-pentanedione. The inactivation of the pyridoxamine phosphate enzyme is not inhibited by substrate analogs. A single lysine residue in the apoenzyme reacts approx. 100 times faster with 2,4-pentanedione than do other amino groups. This lysine is believed to be lysine-258, which forms a Schiff base with pyridoxal phosphate in the holoenzyme.", "contents": "Reversible modification of amino groups in aspartate aminotransferase. Amino  groups in the pyridoxal phosphate, pyridoxamine phosphate, and apo forms of pig heart cytoplasmic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC .2.6.1.1) have been reversibly modified with 2,4-pentanedione. The rate of modification has been measured spectrophotometrically by observing the formation of the enamine produced and this rate has been compared with the rate of loss of catalytic activity for all three forms of the enzyme. Of the 21 amino groups per 46 500 molecular weight, approx. 16 can be modified in the pyridoxal phosphate form with less than a 50% change in the catalytic activity of the enzyme. A slow inactivation occurs which is probably due to reaction of 2,4-pentanedione with the enzyme-bound pyridoxal phosphate. The pyridoxamine phosphate enzyme is completely inactivated by reaction with 2,4-pentanedione. The inactivation of the pyridoxamine phosphate enzyme is not inhibited by substrate analogs. A single lysine residue in the apoenzyme reacts approx. 100 times faster with 2,4-pentanedione than do other amino groups. This lysine is believed to be lysine-258, which forms a Schiff base with pyridoxal phosphate in the holoenzyme."}
{"id": "PMID:18200", "title": "Purification and properties of a triacylglycerol lipase from Mycobacterium phlei.", "content": "In order to study the metabolism of triacylglycerol in mycobacteria, an intracellular particulate triacylglycerol lipase (EC 3.1.1.3) was purified 800-fold from stationary phase cells of Mycobacterium phlei. Extraction of whole cell suspensions with 5% Triton X-100, followed by ion-exchange chromatography of the extract on two successive DEAE-cellulose columns produced a preparation which was nearly homogeneous by the criterion of analytical isoelectric focusing in acrylamide gels (one band, pI. 3.8) and by polyacrylamide gel electrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the preparation into six protein bands. Lipase activity stable to electrophoresis in sodium dodecyl sulfate was extracted from the 40 000 molecular weight region of the gels. ith phosphate or maleate buffer the enzyme exhibits a broad pH optimum around 6.0 with sigmoid saturation kinetics (Hill number 2), and an apparent Km of 8.8 mM  for tripalmitoylglycerol. Citrate and other carboxylic acids increase the apparent V up to 3-fold with the Hill number approaching 1.0. In a series of p-nitrophenyl esters tested (C2-C18), p-nitrophenylmyristate was hydrolyzed most rapidly. The saturation curve for p=nitrophenylmyristate was sigmoid and unaffected by citrate. The role of this activity in the metabolism of triacylglycerols by Mycobacteria is discussed.", "contents": "Purification and properties of a triacylglycerol lipase from Mycobacterium phlei. In order to study the metabolism of triacylglycerol in mycobacteria, an intracellular particulate triacylglycerol lipase (EC 3.1.1.3) was purified 800-fold from stationary phase cells of Mycobacterium phlei. Extraction of whole cell suspensions with 5% Triton X-100, followed by ion-exchange chromatography of the extract on two successive DEAE-cellulose columns produced a preparation which was nearly homogeneous by the criterion of analytical isoelectric focusing in acrylamide gels (one band, pI. 3.8) and by polyacrylamide gel electrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the preparation into six protein bands. Lipase activity stable to electrophoresis in sodium dodecyl sulfate was extracted from the 40 000 molecular weight region of the gels. ith phosphate or maleate buffer the enzyme exhibits a broad pH optimum around 6.0 with sigmoid saturation kinetics (Hill number 2), and an apparent Km of 8.8 mM  for tripalmitoylglycerol. Citrate and other carboxylic acids increase the apparent V up to 3-fold with the Hill number approaching 1.0. In a series of p-nitrophenyl esters tested (C2-C18), p-nitrophenylmyristate was hydrolyzed most rapidly. The saturation curve for p=nitrophenylmyristate was sigmoid and unaffected by citrate. The role of this activity in the metabolism of triacylglycerols by Mycobacteria is discussed."}
{"id": "PMID:18201", "title": "Partial purification and characterization of a triacyglycerol lipase from rat liver cytosol.", "content": "A triacyglycerol lipase (EC 3.1.1.3) was purifiec about 60-fold from rat liver cytosol by delipidation with acetone and ethyl ether, hydroxyapatitie and Sephadex G-100 column chromatographies and isoelectrofocusing electrophoresis. The partially purified enzyme had a molecular weight of approximately 42 000 and an isolectric point of 7.2. The Km for trioleylglycerol was 0.33 mM and the pH optimum was around 8.0. The activity of the enzyme was not dependent on serum lipoproteins, but was stimulated about 2-fold by several proteins such as serum albumin, lipoproteins, gamma-globulin and ovalbumin. The lipase hydrolyzed trioleyglycerol to oleic acid and glycerol. NaCl had no effect on the enzymatic activity. Some physical and kinetic properties of the partially purified lipid-free lipase were different from those of crude non-delipidated lipase and also from those of a neutral triacylglycerol lipase which was recently purified partially from pig liver cytosol (Ledford, J.H. and Alaupovic, P. (1975) Biochim. Biophys. Acta 398, 132-148).", "contents": "Partial purification and characterization of a triacyglycerol lipase from rat liver cytosol. A triacyglycerol lipase (EC 3.1.1.3) was purifiec about 60-fold from rat liver cytosol by delipidation with acetone and ethyl ether, hydroxyapatitie and Sephadex G-100 column chromatographies and isoelectrofocusing electrophoresis. The partially purified enzyme had a molecular weight of approximately 42 000 and an isolectric point of 7.2. The Km for trioleylglycerol was 0.33 mM and the pH optimum was around 8.0. The activity of the enzyme was not dependent on serum lipoproteins, but was stimulated about 2-fold by several proteins such as serum albumin, lipoproteins, gamma-globulin and ovalbumin. The lipase hydrolyzed trioleyglycerol to oleic acid and glycerol. NaCl had no effect on the enzymatic activity. Some physical and kinetic properties of the partially purified lipid-free lipase were different from those of crude non-delipidated lipase and also from those of a neutral triacylglycerol lipase which was recently purified partially from pig liver cytosol (Ledford, J.H. and Alaupovic, P. (1975) Biochim. Biophys. Acta 398, 132-148)."}
{"id": "PMID:18202", "title": "Characteristics of a cytochrome P-450-dependent fatty acid omega-2 hydroxylase from bacillus megaterium.", "content": "The fatty acid (omega-2) hydroxylase from Bacillus megaterium ATCC 14581 was examined with respect to some general enzymatic properties attributed to an intact complex isolated in a partially purified state. Hydroxylase specific activity was found to increase with increasing protein concentration in a manner consistent with a reversible association of the components in the complex. There was a substantial kinetic lag phase for palmitate hydroxylation which was abolished by a substrate preincubation in the absence of NADPH. The substrate bound and presumably activated the hydroxylase complex without the formation of a substrate-derived intermediated. The oxidation of NADPH and the hydroxylation of palmitate were found to occur in a one to one molar ration, independent of the protein concentration. Finally, a cytochrome P-450 component of the complex was identified on the basis of its CO-binding difference spectrum. It appears, that this cytochrome P-450 component is not identical to P-450 meg of the steroid hydroxylase system of B. megaterium ATCC 13368, since progesterone, an active substrate for the latter, is not hydroxylated by the preparation from B. megaterium ATCC 14581.", "contents": "Characteristics of a cytochrome P-450-dependent fatty acid omega-2 hydroxylase from bacillus megaterium. The fatty acid (omega-2) hydroxylase from Bacillus megaterium ATCC 14581 was examined with respect to some general enzymatic properties attributed to an intact complex isolated in a partially purified state. Hydroxylase specific activity was found to increase with increasing protein concentration in a manner consistent with a reversible association of the components in the complex. There was a substantial kinetic lag phase for palmitate hydroxylation which was abolished by a substrate preincubation in the absence of NADPH. The substrate bound and presumably activated the hydroxylase complex without the formation of a substrate-derived intermediated. The oxidation of NADPH and the hydroxylation of palmitate were found to occur in a one to one molar ration, independent of the protein concentration. Finally, a cytochrome P-450 component of the complex was identified on the basis of its CO-binding difference spectrum. It appears, that this cytochrome P-450 component is not identical to P-450 meg of the steroid hydroxylase system of B. megaterium ATCC 13368, since progesterone, an active substrate for the latter, is not hydroxylated by the preparation from B. megaterium ATCC 14581."}
{"id": "PMID:18203", "title": "Influence of hydrogen bonding on the rotamer distribution of the histidine side chain in peptides: 1H NMR and CD studies.", "content": "Both 1H NMR and circular dichroism pH titration studies on histidine, His-Gly, Gly-His and Gly-His-Gly indicate that the side-chain spatial orientation depends strongly on the vicinal charges. The arrangement of the imidazole side-chain (rotamer population) is shown by the histidine beta and beta' and the glycine methylene proton chemical shifts as well as the vicinal 1H-1H coupling constants 3JCalpha-H-beta-H, beta'-H. For His-Gly and Gly-His-Gly a good correlation can be found between the ionization of the glycine COOH group and the increase of rotamer III (g-g) which is also visualized by circular dichroism through an enhancement of the ellipticity at 212 nm. In these two peptides a hydrogen bond between the imidazolium and the carboxylate group is supposed to stabilize rotamer III at pH 4-5.", "contents": "Influence of hydrogen bonding on the rotamer distribution of the histidine side chain in peptides: 1H NMR and CD studies. Both 1H NMR and circular dichroism pH titration studies on histidine, His-Gly, Gly-His and Gly-His-Gly indicate that the side-chain spatial orientation depends strongly on the vicinal charges. The arrangement of the imidazole side-chain (rotamer population) is shown by the histidine beta and beta' and the glycine methylene proton chemical shifts as well as the vicinal 1H-1H coupling constants 3JCalpha-H-beta-H, beta'-H. For His-Gly and Gly-His-Gly a good correlation can be found between the ionization of the glycine COOH group and the increase of rotamer III (g-g) which is also visualized by circular dichroism through an enhancement of the ellipticity at 212 nm. In these two peptides a hydrogen bond between the imidazolium and the carboxylate group is supposed to stabilize rotamer III at pH 4-5."}
{"id": "PMID:18204", "title": "Formation of a complex between yeast L-lactate dehydrogenase (cytochrome b2) and cytochrome c. Ultracentrifugal and gel chromatographic analyses.", "content": "Yeast L-lactate dehydrogenase formed a stable complex with cytochrome c in weakly alkaline solution of low ionic strength. The binding ratio of cytochrome c to the enzyme depended on whether free cytochrome c was present: In the presence of a micromolar concentration of cytochrome c the enzyme formed a complex with about two molecules of cytochrome c, whereas the enzyme was in a 1:1 molecular complex after removal of free cytochrome c. This suggests that the binding of one molecule of cytochrome c changes the affinity of the other binding site on the enzyme for cytochrome c. The enzyme consists of four presumably identical subunits, each containing a binding site for cytochrome c. Thus, present data confirm the concept of negative cooperativity between the subunits of the enzyme molecule in their interaction with cytochrome c.", "contents": "Formation of a complex between yeast L-lactate dehydrogenase (cytochrome b2) and cytochrome c. Ultracentrifugal and gel chromatographic analyses. Yeast L-lactate dehydrogenase formed a stable complex with cytochrome c in weakly alkaline solution of low ionic strength. The binding ratio of cytochrome c to the enzyme depended on whether free cytochrome c was present: In the presence of a micromolar concentration of cytochrome c the enzyme formed a complex with about two molecules of cytochrome c, whereas the enzyme was in a 1:1 molecular complex after removal of free cytochrome c. This suggests that the binding of one molecule of cytochrome c changes the affinity of the other binding site on the enzyme for cytochrome c. The enzyme consists of four presumably identical subunits, each containing a binding site for cytochrome c. Thus, present data confirm the concept of negative cooperativity between the subunits of the enzyme molecule in their interaction with cytochrome c."}
{"id": "PMID:18206", "title": "Conformation of hyaluronate in neutral and alkaline solutions.", "content": "Increasing the pH of a neutral salt solution of sodium hyaluronate to 12.5 produces a rapid drop in viscosity which is reversible upon restoring the pH to neutrality. Light scattering data showing a decrease in radius of gyration with no change in molecular weight and negative results with chondroitin and other acidic glycosaminoglycans suggest that the conformational change is specific for hyaluronate molecules.", "contents": "Conformation of hyaluronate in neutral and alkaline solutions. Increasing the pH of a neutral salt solution of sodium hyaluronate to 12.5 produces a rapid drop in viscosity which is reversible upon restoring the pH to neutrality. Light scattering data showing a decrease in radius of gyration with no change in molecular weight and negative results with chondroitin and other acidic glycosaminoglycans suggest that the conformational change is specific for hyaluronate molecules."}
{"id": "PMID:18207", "title": "Cyclic AMP-dependent control of the rat hepatic glutathione disulfide-sulfhydryl ratio.", "content": "The disulfide-sulfhydryl ratio of rat hepatic tissue has been found to vary diurnally lowest in the early morning and highest in the early evening (Isaacs, J. (1976) Fed. Proc. 35, 1472, and Isaacs, J. and Binkley, F. (1977) Biochim. Biophys. Acta 497, 192-204). Intraperitoneal injections of dibutyryl cyclic AMP induces an increase in hepatic glutathione protein mixed disulfides (GSSProt) combined with a corresponding decrease in reduced glutathione (GSH) and protein sulfhydryl (ProtSH). Also, dibutyryl cyclic AMP caused hepatic catalase activity to decrease and to increase hepatic production of peroxide molecules. A decrease in catalase activity directs more of the increased peroxide into the glutathione peroxidase pathway. This leads to increased amounts of oxidized glutathione (GSSG) which ultimately results in increased levels of GSSProt. Therefore cyclic AMP may mediate its effect on the disulfide-sulfhydryl ratio via control over catalase and peroxide generation. Support for this idea is provided by the close temporal correlation between the diurnal variations in cyclic AMP, hepatic catalase, peroxide generation and GSSProt-GSH levels.", "contents": "Cyclic AMP-dependent control of the rat hepatic glutathione disulfide-sulfhydryl ratio. The disulfide-sulfhydryl ratio of rat hepatic tissue has been found to vary diurnally lowest in the early morning and highest in the early evening (Isaacs, J. (1976) Fed. Proc. 35, 1472, and Isaacs, J. and Binkley, F. (1977) Biochim. Biophys. Acta 497, 192-204). Intraperitoneal injections of dibutyryl cyclic AMP induces an increase in hepatic glutathione protein mixed disulfides (GSSProt) combined with a corresponding decrease in reduced glutathione (GSH) and protein sulfhydryl (ProtSH). Also, dibutyryl cyclic AMP caused hepatic catalase activity to decrease and to increase hepatic production of peroxide molecules. A decrease in catalase activity directs more of the increased peroxide into the glutathione peroxidase pathway. This leads to increased amounts of oxidized glutathione (GSSG) which ultimately results in increased levels of GSSProt. Therefore cyclic AMP may mediate its effect on the disulfide-sulfhydryl ratio via control over catalase and peroxide generation. Support for this idea is provided by the close temporal correlation between the diurnal variations in cyclic AMP, hepatic catalase, peroxide generation and GSSProt-GSH levels."}
{"id": "PMID:18208", "title": "Effects of guanosine on insulin secretion and adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans.", "content": "The effect of guanosine on insulin secretion, adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans was investigated. Guanosine (1-100 micron) inhibited glucose, tolbutamide, theophylline and prostaglandin E2-stimulated insulin secretion although it failed to affect glucagon stimulated secretion. Prostaglandin E2-stimulated adenylyl cyclase activity of islets was inhibited by guanosine although guanosine had no effect on basal, fluoride, glucagon or GTP-stimulated activity. Guanosine markedly decreased basal guanylyl cyclase activity of islets. These results suggest that guanosine may affect insulin release by inhibiting adenylyl and guanylyl cyclase activities in the beta-cell thereby decreasing the intracellular concentrations of cyclic nucleotides. This effect may be important in modulating the secretory response of the islets to a variety of hormonal agents.", "contents": "Effects of guanosine on insulin secretion and adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans. The effect of guanosine on insulin secretion, adenylyl and guanylyl cyclase activities of isolated rat islets of Langerhans was investigated. Guanosine (1-100 micron) inhibited glucose, tolbutamide, theophylline and prostaglandin E2-stimulated insulin secretion although it failed to affect glucagon stimulated secretion. Prostaglandin E2-stimulated adenylyl cyclase activity of islets was inhibited by guanosine although guanosine had no effect on basal, fluoride, glucagon or GTP-stimulated activity. Guanosine markedly decreased basal guanylyl cyclase activity of islets. These results suggest that guanosine may affect insulin release by inhibiting adenylyl and guanylyl cyclase activities in the beta-cell thereby decreasing the intracellular concentrations of cyclic nucleotides. This effect may be important in modulating the secretory response of the islets to a variety of hormonal agents."}
{"id": "PMID:18209", "title": "Incorporation of mannose and glucose into prenylphosphate sugars in isolated human platelet membranes.", "content": "Isolated platelet membranes synthesize mannosylretinyl phosphate and dolichylmannosyl phosphate from GDP-[14C]mannose, but only dolichylglucosyl-phosphate is synthesized from UDP-[14C]glucose. Addition of exogenous retinylphosphate specifically stimulates the biosynthesis of mannosylretinylphosphate.", "contents": "Incorporation of mannose and glucose into prenylphosphate sugars in isolated human platelet membranes. Isolated platelet membranes synthesize mannosylretinyl phosphate and dolichylmannosyl phosphate from GDP-[14C]mannose, but only dolichylglucosyl-phosphate is synthesized from UDP-[14C]glucose. Addition of exogenous retinylphosphate specifically stimulates the biosynthesis of mannosylretinylphosphate."}
{"id": "PMID:18210", "title": "The reaction of superoxide radical with iron complexes of EDTA studied by pulse radiolysis.", "content": "The reactions of Fe3+-EDTA and Fe2+-EDTA with O2- and CO2- were investigated in the pH range 3.8--11.8. Around neutral pH O2- reduces Fe3+-EDTA with a rate constant which is pH dependent kpH 5.8--8.1 = 2 - 10(6)--5 - 10(5) M-1 - s-1. At higher pH values this reaction becomes much slower. The CO2- radical reduces Fe3+-EDTA with kpH 3.8--1- = 5 +/- 1 - 10(7) M-1 - s-1 independent of pH. At pH 9--11.8, Fe2+-EDTA forms a complex with O2- with kFe2+-EDTA + O2 = 2 - 10(6)--4 - 10(6) M-1 - s-1 which is pH dependent. We measured the spectrum of Fe2+-EDTA-O2- and calculated epsilon 290 over max = 6400 +/- 800 M-1 - cm-1 in air-saturated solutions. In O2-saturated solutions another species is formed with a rate constant of 7 +/- 2 s-1. This intermediate absorbs around 300 nm but we were not able to identify it.", "contents": "The reaction of superoxide radical with iron complexes of EDTA studied by pulse radiolysis. The reactions of Fe3+-EDTA and Fe2+-EDTA with O2- and CO2- were investigated in the pH range 3.8--11.8. Around neutral pH O2- reduces Fe3+-EDTA with a rate constant which is pH dependent kpH 5.8--8.1 = 2 - 10(6)--5 - 10(5) M-1 - s-1. At higher pH values this reaction becomes much slower. The CO2- radical reduces Fe3+-EDTA with kpH 3.8--1- = 5 +/- 1 - 10(7) M-1 - s-1 independent of pH. At pH 9--11.8, Fe2+-EDTA forms a complex with O2- with kFe2+-EDTA + O2 = 2 - 10(6)--4 - 10(6) M-1 - s-1 which is pH dependent. We measured the spectrum of Fe2+-EDTA-O2- and calculated epsilon 290 over max = 6400 +/- 800 M-1 - cm-1 in air-saturated solutions. In O2-saturated solutions another species is formed with a rate constant of 7 +/- 2 s-1. This intermediate absorbs around 300 nm but we were not able to identify it."}
{"id": "PMID:18211", "title": "Interconversion of multiple forms of tyrosine aminotransferase in vitro and in vivo in cultured hepatoma cells.", "content": "Corticosteroid-induced tyrosine aminotransferase (EC 2.6.1.5) from cultured hepatoma cells was separated by carboxymethyl-Sephadex chromatography into three molecular forms resembling those described previously in the rat liver. Enzyme forms were isolated and used as purified substrates to examine their in vitro interconversion by various subcellular fractions. Isolated form III was converted to forms II and I, and isolated form II was converted to form I by the coarse particulate fraction sedimenting at 1000 X g. This activity was inhibited by the serine enzyme inhibitor phenylmethane sulfonyl fluoride or by raising the pH to 8.7. Conversion of enzyme forms in vitro in the opposite direction (I leads to II leads to III) could not be detected. The distribution of enzyme forms in vivo was examined by the use of experimental conditions that prevent their in vitro interconversion during cell extraction. Tyrosine aminotransferase extracted from cell subjected to various treatments that affect the rates of enzyme synthesis or degradation existed always predominantly as form III. It appears, therefore, that multiple forms of tyrosine aminotransferase are not related to the turnover of this enzyme in vivo.", "contents": "Interconversion of multiple forms of tyrosine aminotransferase in vitro and in vivo in cultured hepatoma cells. Corticosteroid-induced tyrosine aminotransferase (EC 2.6.1.5) from cultured hepatoma cells was separated by carboxymethyl-Sephadex chromatography into three molecular forms resembling those described previously in the rat liver. Enzyme forms were isolated and used as purified substrates to examine their in vitro interconversion by various subcellular fractions. Isolated form III was converted to forms II and I, and isolated form II was converted to form I by the coarse particulate fraction sedimenting at 1000 X g. This activity was inhibited by the serine enzyme inhibitor phenylmethane sulfonyl fluoride or by raising the pH to 8.7. Conversion of enzyme forms in vitro in the opposite direction (I leads to II leads to III) could not be detected. The distribution of enzyme forms in vivo was examined by the use of experimental conditions that prevent their in vitro interconversion during cell extraction. Tyrosine aminotransferase extracted from cell subjected to various treatments that affect the rates of enzyme synthesis or degradation existed always predominantly as form III. It appears, therefore, that multiple forms of tyrosine aminotransferase are not related to the turnover of this enzyme in vivo."}
{"id": "PMID:18212", "title": "Studies of Zn(II) and Co(II) complexes of imidazole and n-methylimidazole with regard to the activity related ionization in carbonic anhydrase.", "content": "Mixed aquo-N-methylimidazole complexes of Co(II) have been studied as a function of pH to gain a fuller understanding of the metal-binding site in Co(II)-carbonic anhydrase. The inherent affinity of N-methylimidazole for Co(II) has been calculated along with a species distribution for the stepwise addition of ligand to the metal ion. From these studies, it is apparent that the occurrence of Zn(II) rather than Co(II) in native carbonic anhydrase can be explained by the stronger affinity of Zn(II) for imidazole and the preference of Zn(II) for a tetrahedral geometry as offered by the enzyme. Octahedral Co(II) fails to ionize metal bound water. However, at high pH, Co(II)-N-methylimidazole complexes interact directly with the hydroxide ion, generating species with visible spectra very similar to that of Co(II)-carbonic anhydrase. Tentative structures have been proposed for these species.", "contents": "Studies of Zn(II) and Co(II) complexes of imidazole and n-methylimidazole with regard to the activity related ionization in carbonic anhydrase. Mixed aquo-N-methylimidazole complexes of Co(II) have been studied as a function of pH to gain a fuller understanding of the metal-binding site in Co(II)-carbonic anhydrase. The inherent affinity of N-methylimidazole for Co(II) has been calculated along with a species distribution for the stepwise addition of ligand to the metal ion. From these studies, it is apparent that the occurrence of Zn(II) rather than Co(II) in native carbonic anhydrase can be explained by the stronger affinity of Zn(II) for imidazole and the preference of Zn(II) for a tetrahedral geometry as offered by the enzyme. Octahedral Co(II) fails to ionize metal bound water. However, at high pH, Co(II)-N-methylimidazole complexes interact directly with the hydroxide ion, generating species with visible spectra very similar to that of Co(II)-carbonic anhydrase. Tentative structures have been proposed for these species."}
{"id": "PMID:18213", "title": "Interactions between alpha-amino acids and cobalt(II) bovine-carbonic anhydrase.", "content": "The results of a study on the interaction between cobalt(II) bovine carbonic anhydrase and the alpha-amino acids L(+) and D(-)alanine, glycine and betaine are reported. L(+)alanine and glycine have been found to have larger affinity for the enzyme than D(-)alanine whereas no sizable affinity is shown by betaine. The electronic spectra indicate that these systems are similar to that containing the acetate ion. Utilizing the inhibition properties of L(+)alanine at various pH an analysis of the species involved in the inhibition reaction is presented.", "contents": "Interactions between alpha-amino acids and cobalt(II) bovine-carbonic anhydrase. The results of a study on the interaction between cobalt(II) bovine carbonic anhydrase and the alpha-amino acids L(+) and D(-)alanine, glycine and betaine are reported. L(+)alanine and glycine have been found to have larger affinity for the enzyme than D(-)alanine whereas no sizable affinity is shown by betaine. The electronic spectra indicate that these systems are similar to that containing the acetate ion. Utilizing the inhibition properties of L(+)alanine at various pH an analysis of the species involved in the inhibition reaction is presented."}
{"id": "PMID:18214", "title": "Circularly polarized emission studies on Tb3+ and Eu3+ complexes with potentially terdentate amino acids in aqueous solution.", "content": "Circularly polarized emission (CPE) and total emission (TE) spectra are reported for Eu3+ and Tb3+ complexes of L-aspartic acid (L-asp), L-serine (L-ser), L-threonine (L-thr) and L-histidine (L-his) in D2O solution under various pH conditions. Variations in TE and CPE intensities and in CPE splittings and sign patterns as functions of solution pH are correlated with lanthanide ion/ligand binding characteristics and with structural changes in the coordination environment of the metal ion. In the Eu3+/amino acid systems, the emission bands associated with the 5D0 leads to 7F1 and 7F2 Eu3+ transitions are monitored, and in the Tb3+/amino acid systems the 5D4 leads to 7F5 Tb3+ emission is examined.", "contents": "Circularly polarized emission studies on Tb3+ and Eu3+ complexes with potentially terdentate amino acids in aqueous solution. Circularly polarized emission (CPE) and total emission (TE) spectra are reported for Eu3+ and Tb3+ complexes of L-aspartic acid (L-asp), L-serine (L-ser), L-threonine (L-thr) and L-histidine (L-his) in D2O solution under various pH conditions. Variations in TE and CPE intensities and in CPE splittings and sign patterns as functions of solution pH are correlated with lanthanide ion/ligand binding characteristics and with structural changes in the coordination environment of the metal ion. In the Eu3+/amino acid systems, the emission bands associated with the 5D0 leads to 7F1 and 7F2 Eu3+ transitions are monitored, and in the Tb3+/amino acid systems the 5D4 leads to 7F5 Tb3+ emission is examined."}
{"id": "PMID:18215", "title": "Heavy metal-nucleotide interactions. IX. Raman difference spectroscopic studies on the binding of CH3Hg(II) to 1-methylthymine, thymidine-5'-monophosphate, DNA models and native DNA.", "content": "Raman spectra have been obtained for dTMP and its complex with CH3Hg (II) in aqueous solution as a function of pH. Difference spectroscopy is employed to increase the sensitivity of the Raman technique. The binding reaction is essentially quantitative from pH 3 to 9, and the value of the equilibrium constant for CH3HgOH2+ + dThd in equilibrium CH3Hg(dThdH--1) + H30+ is estimated from intensity measurements to be 0.6 in reasonable agreement with an earlier value based upon uv spectrophotometric data. Binding is to N(3) with substitution of CH3Hg+ for the proton. A similar reaction occurs with 1-MeThy. Raman spectra for aqueous and crystalline 1-MeThy and for the complex CH3Hg(1-MeThyH--1) are reported. The spectrum of crystalline Hg(1-MeThyH--1)2, for which the crystal structure is known, also was obtained for comparison. Raman difference spectroscopy was used to confirm that CH3Hg (II) binds to N(3) of dTMP and N(1) of GMP at r = 0.2 (MeHg+: phosphate) ratios with mixtures of GMP + CMP + AMP + dTMP. In contrast, native calf thymus DNA does not appear to bind CH3Hg(II) at these sites at r = 0.15, although no significant amount of free CH3HgOH is present. With r = 0.3, extensive binding occurs both to the Thy and Gua bases. Raman difference spectroscopy is a valuable technique for studying the binding of ions and molecules to polynucleotides in moderately dilute aqueous solution.", "contents": "Heavy metal-nucleotide interactions. IX. Raman difference spectroscopic studies on the binding of CH3Hg(II) to 1-methylthymine, thymidine-5'-monophosphate, DNA models and native DNA. Raman spectra have been obtained for dTMP and its complex with CH3Hg (II) in aqueous solution as a function of pH. Difference spectroscopy is employed to increase the sensitivity of the Raman technique. The binding reaction is essentially quantitative from pH 3 to 9, and the value of the equilibrium constant for CH3HgOH2+ + dThd in equilibrium CH3Hg(dThdH--1) + H30+ is estimated from intensity measurements to be 0.6 in reasonable agreement with an earlier value based upon uv spectrophotometric data. Binding is to N(3) with substitution of CH3Hg+ for the proton. A similar reaction occurs with 1-MeThy. Raman spectra for aqueous and crystalline 1-MeThy and for the complex CH3Hg(1-MeThyH--1) are reported. The spectrum of crystalline Hg(1-MeThyH--1)2, for which the crystal structure is known, also was obtained for comparison. Raman difference spectroscopy was used to confirm that CH3Hg (II) binds to N(3) of dTMP and N(1) of GMP at r = 0.2 (MeHg+: phosphate) ratios with mixtures of GMP + CMP + AMP + dTMP. In contrast, native calf thymus DNA does not appear to bind CH3Hg(II) at these sites at r = 0.15, although no significant amount of free CH3HgOH is present. With r = 0.3, extensive binding occurs both to the Thy and Gua bases. Raman difference spectroscopy is a valuable technique for studying the binding of ions and molecules to polynucleotides in moderately dilute aqueous solution."}
{"id": "PMID:18216", "title": "[Phospholipase of rat intestine: mode of action].", "content": "Phospholipase activities of rat intestinal mucosa homogenate have been determined from lysophosphatidylcholines [14C] and phosphatidylcholines [-3H-14C]. In the presence of phosphatidylcholines, at pH 6.5, the homogenate has a phospholipase B activity. At  pH 8.5, a phospholipase A2 activity was shown. In the presence of lysophospatidylcholines, at pH 6.5, we notice a lysophospholipase A1 activity. A kinetic study of the reactions allows us to separate the activity B into a phospholipase A2 activity and a lysophospholipase A1 activity. Thus, it appears that the total phospholipase activity of rat intestinal mucosa would results from a phospholipase A2 activity and a lysophospholipase A1 activity.", "contents": "[Phospholipase of rat intestine: mode of action]. Phospholipase activities of rat intestinal mucosa homogenate have been determined from lysophosphatidylcholines [14C] and phosphatidylcholines [-3H-14C]. In the presence of phosphatidylcholines, at pH 6.5, the homogenate has a phospholipase B activity. At  pH 8.5, a phospholipase A2 activity was shown. In the presence of lysophospatidylcholines, at pH 6.5, we notice a lysophospholipase A1 activity. A kinetic study of the reactions allows us to separate the activity B into a phospholipase A2 activity and a lysophospholipase A1 activity. Thus, it appears that the total phospholipase activity of rat intestinal mucosa would results from a phospholipase A2 activity and a lysophospholipase A1 activity."}
{"id": "PMID:18219", "title": "Ionic permeability of K, Na, and Cl in crayfish nerve. Regulation by membrane fixed charges and pH.", "content": "Teorell's fixed charge theory for membrane ion permeability was utilized to calculate specific ionic permeabilities from measurements of membrane potential, conductance, and specific ionic transference numbers. The results were compared with the passive ionic conductances calculated from the branched equivalent circuit membrane model of Hodgkin Huxley. Ionic permeabilities for potassium, sodium, and chloride of crayfish (Procambarus clarkii) medial giant axons were examined over an external pH range from 3.8 to 11.4. Action potentials were obtained over this pH range. Failures occurred below pH 3.8 during protonation of membrane phospholipid phosphate and carboxyl, and above pH 11.4 from calcium precipitation. In general, chloride permeability increases with membrane protonation, while cation permeability  decreases. At pH 7.0, PK = 1.33 X 10(-5), PCl = 1.49 X 10(-6), PNa = 1.92 X 10(-8) cm/s. PK: PCl: PNa = 693:78:1. PCl is zero above pH 10.6 and is opened predominately by protonation of epsilon-amino, and partially by tyrosine and sulfhydryl groups from pH 10.6 to 9. PK is activated in part by ionization of phospholipid phosphate and carboxyl around pH 4, then further by imidazole from pH 5 to 7, and then predominately from pH 7 to 9 by most probably phosphatidic acid. PNa permeability parallels that of potassium from pH 5 to 9.4. Below pH 5 and above pH 9.4, PNa increases while PK decreases. Evidence was obtained that these ions possibly share common passive permeable channels. The data best support the theory of Teorell, that membrane fixed charges regulate permiability and that essentially every membrane ionizable group appears involved in various amounts in ionic permeability control.", "contents": "Ionic permeability of K, Na, and Cl in crayfish nerve. Regulation by membrane fixed charges and pH. Teorell's fixed charge theory for membrane ion permeability was utilized to calculate specific ionic permeabilities from measurements of membrane potential, conductance, and specific ionic transference numbers. The results were compared with the passive ionic conductances calculated from the branched equivalent circuit membrane model of Hodgkin Huxley. Ionic permeabilities for potassium, sodium, and chloride of crayfish (Procambarus clarkii) medial giant axons were examined over an external pH range from 3.8 to 11.4. Action potentials were obtained over this pH range. Failures occurred below pH 3.8 during protonation of membrane phospholipid phosphate and carboxyl, and above pH 11.4 from calcium precipitation. In general, chloride permeability increases with membrane protonation, while cation permeability  decreases. At pH 7.0, PK = 1.33 X 10(-5), PCl = 1.49 X 10(-6), PNa = 1.92 X 10(-8) cm/s. PK: PCl: PNa = 693:78:1. PCl is zero above pH 10.6 and is opened predominately by protonation of epsilon-amino, and partially by tyrosine and sulfhydryl groups from pH 10.6 to 9. PK is activated in part by ionization of phospholipid phosphate and carboxyl around pH 4, then further by imidazole from pH 5 to 7, and then predominately from pH 7 to 9 by most probably phosphatidic acid. PNa permeability parallels that of potassium from pH 5 to 9.4. Below pH 5 and above pH 9.4, PNa increases while PK decreases. Evidence was obtained that these ions possibly share common passive permeable channels. The data best support the theory of Teorell, that membrane fixed charges regulate permiability and that essentially every membrane ionizable group appears involved in various amounts in ionic permeability control."}
{"id": "PMID:18220", "title": "Swelling of skinned muscle fibers of the frog. Experimental observations.", "content": "Frog skeletal muscle fibers, mechanically skinned under water-saturated silicone oil, swell upon transfer to aqueous relaxing medium (60 mM KCl; 3 mM MgCl(2); 3 mM ATP; 4 mM EGTA; 20 mM Tris maleate; pH = 7.0; ionic strength 0.15 M). Their cross-sectional areas, estimated with an elliptical approximation, increase 2.32-fold (+/-0.54 SD). Sarcomere spacing is unaffected by this swelling. Addition of 200 mM sucrose to relaxing medium had no effect on fiber dimensions, whereas decreasing pH to 5.0 caused fibers to shrink nearly to their original (oil) size. Decreasing MgCl(2) to 0.3 mM caused fibers to swell 10%, and increasing MgCl(2) to 9 mM led to an 8% shrinkage. Increasing ionic strength to 0.29 M with KCl caused a 26% increase in cross-sectional area; decreasing ionic strength to 0.09 M had no effect. Swelling pressure was estimated with long-chain polymers, which are probably excluded from the myofilament lattice. Shrinkage in dextran T10 (number average mol wt 6,200) was transient, indicating that this polymer may penetrate into the fibers. Shrinkage in dextran T40 (number average mol wt 28,000), polyvinylpyrrolidone (PVP) K30 (number average mol wt 40,000) and dextran T70 (number average mol wt 40,300) was not transient, indicating exclusion. Maximal calcium-activated tension is decreased by 21% in PVP solutions and by 31% in dextran T40 solutions. Fibers were shrunk to their original size with 8 x 10(-2) g/cm(3) PVP K30, a concentration which, from osmometric data, corresponds to an osmotic pressure (II/RT) of 10.5 mM. As discussed in the text, we consider this our best estimate of the swelling pressure. We find that increasing ionic strength to 0.39 M with KCl decreases swelling pressure slightly, whereas decreasing ionic strength to 0.09 M has no effect. We feel these data are consistent with the idea that swelling arises from the negatively charged nature of the myofilaments, from either mutual filamentary repulsion or a Donnan-osmotic mechanism.", "contents": "Swelling of skinned muscle fibers of the frog. Experimental observations. Frog skeletal muscle fibers, mechanically skinned under water-saturated silicone oil, swell upon transfer to aqueous relaxing medium (60 mM KCl; 3 mM MgCl(2); 3 mM ATP; 4 mM EGTA; 20 mM Tris maleate; pH = 7.0; ionic strength 0.15 M). Their cross-sectional areas, estimated with an elliptical approximation, increase 2.32-fold (+/-0.54 SD). Sarcomere spacing is unaffected by this swelling. Addition of 200 mM sucrose to relaxing medium had no effect on fiber dimensions, whereas decreasing pH to 5.0 caused fibers to shrink nearly to their original (oil) size. Decreasing MgCl(2) to 0.3 mM caused fibers to swell 10%, and increasing MgCl(2) to 9 mM led to an 8% shrinkage. Increasing ionic strength to 0.29 M with KCl caused a 26% increase in cross-sectional area; decreasing ionic strength to 0.09 M had no effect. Swelling pressure was estimated with long-chain polymers, which are probably excluded from the myofilament lattice. Shrinkage in dextran T10 (number average mol wt 6,200) was transient, indicating that this polymer may penetrate into the fibers. Shrinkage in dextran T40 (number average mol wt 28,000), polyvinylpyrrolidone (PVP) K30 (number average mol wt 40,000) and dextran T70 (number average mol wt 40,300) was not transient, indicating exclusion. Maximal calcium-activated tension is decreased by 21% in PVP solutions and by 31% in dextran T40 solutions. Fibers were shrunk to their original size with 8 x 10(-2) g/cm(3) PVP K30, a concentration which, from osmometric data, corresponds to an osmotic pressure (II/RT) of 10.5 mM. As discussed in the text, we consider this our best estimate of the swelling pressure. We find that increasing ionic strength to 0.39 M with KCl decreases swelling pressure slightly, whereas decreasing ionic strength to 0.09 M has no effect. We feel these data are consistent with the idea that swelling arises from the negatively charged nature of the myofilaments, from either mutual filamentary repulsion or a Donnan-osmotic mechanism."}
{"id": "PMID:18223", "title": "Tyrosine fluorescence of two tryptophan-free proteins: histones H1 and H5.", "content": "The fluorescence intensity of the single tyrosine residue in histone H1 increases from RTYR = 0.3 to RTYR = 1.3 as the protein undergoes a conformational change from the random coil state to a folded form. Enhanced fluorescence in the folded state has not been observed before in ap protein. Histone H5 shows no change in fluorescence intensity on folding. This is interpreted as a result of compensation between enhanced and reduced fluorescence in the three tyrosine residues.", "contents": "Tyrosine fluorescence of two tryptophan-free proteins: histones H1 and H5. The fluorescence intensity of the single tyrosine residue in histone H1 increases from RTYR = 0.3 to RTYR = 1.3 as the protein undergoes a conformational change from the random coil state to a folded form. Enhanced fluorescence in the folded state has not been observed before in ap protein. Histone H5 shows no change in fluorescence intensity on folding. This is interpreted as a result of compensation between enhanced and reduced fluorescence in the three tyrosine residues."}
{"id": "PMID:18226", "title": "Quantitative determination of enantiomeric compounds. I--Simultaneous measurement of the optical isomers of amphetamine in human plasma and saliva using chemical ionization mass spectrometry.", "content": "A sensitive and specific method for the quantitative determination of the optical isomers of amphetamine from human plasma and saliva is described. Amphetamine was extracted from basified plasma or saliva with hexane and then derivatized by reaction with N-pentafluorobenzoyl-S-(-)-prolyl-1-imidazolide. The reaction of the amphetamine enantiomers with this chiral reagent yields diasteriomers which are easily resolved by gas liquid chromatography. The resolved diasteriomers upon elution from the gas chromatograph were measured quantitatively by chemical ionization mass spectrometry. Plasma and saliva levels achieved following the oral administration of 10 mg of dl-, d- and l-amphetamine in man are reported.", "contents": "Quantitative determination of enantiomeric compounds. I--Simultaneous measurement of the optical isomers of amphetamine in human plasma and saliva using chemical ionization mass spectrometry. A sensitive and specific method for the quantitative determination of the optical isomers of amphetamine from human plasma and saliva is described. Amphetamine was extracted from basified plasma or saliva with hexane and then derivatized by reaction with N-pentafluorobenzoyl-S-(-)-prolyl-1-imidazolide. The reaction of the amphetamine enantiomers with this chiral reagent yields diasteriomers which are easily resolved by gas liquid chromatography. The resolved diasteriomers upon elution from the gas chromatograph were measured quantitatively by chemical ionization mass spectrometry. Plasma and saliva levels achieved following the oral administration of 10 mg of dl-, d- and l-amphetamine in man are reported."}
{"id": "PMID:18228", "title": "Possible origin of gating current in nerve membrane.", "content": "The present information about gating current observed in squid giant axons points towards the distinct possibility of the current arising from the Debye relaxation of the carboxyl groups in the side chains of the globular proteins enclosing the ionic channels. These carboxyl groups form dipole chains stretching across the membrane. A dipole model is constructed to study the relaxation process under the assumption that the relaxation time  tau of the dipoles is modified by dipole-dipole interaction. This model explains qualitatively some of the features of the asymmetric gating current, but is not indicative of any specific mechanism leading to the opening of the gates in the ionic channels. We speculate that the conformational change in the protein globules as a result of dipole reorientation would be the key to the mystery.", "contents": "Possible origin of gating current in nerve membrane. The present information about gating current observed in squid giant axons points towards the distinct possibility of the current arising from the Debye relaxation of the carboxyl groups in the side chains of the globular proteins enclosing the ionic channels. These carboxyl groups form dipole chains stretching across the membrane. A dipole model is constructed to study the relaxation process under the assumption that the relaxation time  tau of the dipoles is modified by dipole-dipole interaction. This model explains qualitatively some of the features of the asymmetric gating current, but is not indicative of any specific mechanism leading to the opening of the gates in the ionic channels. We speculate that the conformational change in the protein globules as a result of dipole reorientation would be the key to the mystery."}
{"id": "PMID:18229", "title": "Thermodynamics of the binding of flavin adenine dinucleotide to D-amino acid oxidase.", "content": "The enthalpy of binding, deltaHb, of flavin adenine dinucleotide to the apoenzyme of D-amino acid oxidase was determined by flow calorimetry at pH 8.5 to be +3.8, -4.1 and -11.0 kcal mol-1 at 10 degrees, 25 degrees and 38 degrees, respectively. These values correspond to a heat capacity change, deltaCp, of -530 cal K-1 mol-1. From the binding constant reported by Dixon and Kleppe (1965a) and the above enthalpies, the standard free energy and standard entropy of binding are evaluated. These thermodynamic data are interpreted in terms of hydrophobic and vibrational contributions (Sturtevant, 1977). The product of the assay reaction (Fonda and Anderson, 1967), benzoylformic acid, is a non-competitive inhibitor of the enzyme with a value for KI of 1.4 X 10(-4)M at 25 degrees.", "contents": "Thermodynamics of the binding of flavin adenine dinucleotide to D-amino acid oxidase. The enthalpy of binding, deltaHb, of flavin adenine dinucleotide to the apoenzyme of D-amino acid oxidase was determined by flow calorimetry at pH 8.5 to be +3.8, -4.1 and -11.0 kcal mol-1 at 10 degrees, 25 degrees and 38 degrees, respectively. These values correspond to a heat capacity change, deltaCp, of -530 cal K-1 mol-1. From the binding constant reported by Dixon and Kleppe (1965a) and the above enthalpies, the standard free energy and standard entropy of binding are evaluated. These thermodynamic data are interpreted in terms of hydrophobic and vibrational contributions (Sturtevant, 1977). The product of the assay reaction (Fonda and Anderson, 1967), benzoylformic acid, is a non-competitive inhibitor of the enzyme with a value for KI of 1.4 X 10(-4)M at 25 degrees."}
{"id": "PMID:18230", "title": "Simultaneous peptide and oligonucleotide formation in mixtures of amino acid, nucleoside triphosphate, imidazole, and magnesium ion.", "content": "Simultaneous peptide and oligonucleotide formation was observed in reaction mixtures of amino acid, nucleoside triphosphate, imidazole, and MgCl2. At 70 degrees C in solutions that were evaporated to dryness the formation of peptide for phe and pro was greatest with CTP relative to ATP, GTP, and UTP. Lysine exhibited a preference for GTP and glycine for UTP. At ambient temperature insolution at pH 7.8, CTP was preferred by glycine, but at pH 8.7 UTP was preferred. The glycine nucleotide phosphoramidates were also detected and characterized in reactions at 40 degrees C. The glycine-reaction preference for CTP at pH 7.8 and UTP at 8.7 suggested that the basicity of the nucleoside triphosphate was involved in increasing the peptide yield. CTP near neutrality is the most basic nucleoside triphosphate and the basic anionic form UTP could facilitate peptide formation at pH 8.7. These data, together with information on the complexing of poly(C) by GTP, led to the experimentally approchable hypothesis that GTP, by forming a basic triplex between the cytosine residues adjacent to the peptidyl adenosine and aminoacyl adenosine at the termini of two proto-tRNAs, would promote peptide bond synthesis between the aminoacyl residue and peptidyl residue.", "contents": "Simultaneous peptide and oligonucleotide formation in mixtures of amino acid, nucleoside triphosphate, imidazole, and magnesium ion. Simultaneous peptide and oligonucleotide formation was observed in reaction mixtures of amino acid, nucleoside triphosphate, imidazole, and MgCl2. At 70 degrees C in solutions that were evaporated to dryness the formation of peptide for phe and pro was greatest with CTP relative to ATP, GTP, and UTP. Lysine exhibited a preference for GTP and glycine for UTP. At ambient temperature insolution at pH 7.8, CTP was preferred by glycine, but at pH 8.7 UTP was preferred. The glycine nucleotide phosphoramidates were also detected and characterized in reactions at 40 degrees C. The glycine-reaction preference for CTP at pH 7.8 and UTP at 8.7 suggested that the basicity of the nucleoside triphosphate was involved in increasing the peptide yield. CTP near neutrality is the most basic nucleoside triphosphate and the basic anionic form UTP could facilitate peptide formation at pH 8.7. These data, together with information on the complexing of poly(C) by GTP, led to the experimentally approchable hypothesis that GTP, by forming a basic triplex between the cytosine residues adjacent to the peptidyl adenosine and aminoacyl adenosine at the termini of two proto-tRNAs, would promote peptide bond synthesis between the aminoacyl residue and peptidyl residue."}
{"id": "PMID:18231", "title": "Amperometric assay of coenzyme-dependent oxidoreductase enzymes in a flow-through cell.", "content": "We have demonstrated that a simple electrochemical cell can serve as a detector of NADH concentration in a flow system thereby providing an assay technique for NADH dependent enzymes. When this is applied to NADH produced by enzymatic reaction, then a reproducible measure of enzyme activity is obtained. This method of enzyme activity assay is applicable to a number of oxidoreductase enzymes which employ NAD+ or NADP+ as coenzymes to achieve substrate modification. The presence of electroactive species in samples of human serum has proved a serious problem in the electrochemical analysis of serum activity. These species produce a large background anode current at the anode voltage appropriate for NADH oxidation. The presence of this high current limits the usefulness of amplification of the current output to detect small changes in NADH concentration.", "contents": "Amperometric assay of coenzyme-dependent oxidoreductase enzymes in a flow-through cell. We have demonstrated that a simple electrochemical cell can serve as a detector of NADH concentration in a flow system thereby providing an assay technique for NADH dependent enzymes. When this is applied to NADH produced by enzymatic reaction, then a reproducible measure of enzyme activity is obtained. This method of enzyme activity assay is applicable to a number of oxidoreductase enzymes which employ NAD+ or NADP+ as coenzymes to achieve substrate modification. The presence of electroactive species in samples of human serum has proved a serious problem in the electrochemical analysis of serum activity. These species produce a large background anode current at the anode voltage appropriate for NADH oxidation. The presence of this high current limits the usefulness of amplification of the current output to detect small changes in NADH concentration."}
{"id": "PMID:18233", "title": "Growth kinetics and cellulase biosynthesis in the continuous culture of Trichoderma viride.", "content": "Continuous culture studies have been carried out growing Trichoderma viride QM 9123 in a 10 liter stirred fermentor on a medium containing commercial glucose as the carbon source. Experiments were carried out at 30 degrees C and at three controlled pH values of 2.5, 3.0, and 4.0 over a range of dilution rates from 0.01 to 0.11 hr-1. Steady-state values of cell, glucose, and cellulase concentration oxygen tension, and outlet gas oxygen partial pressure were recorded. Values of maximum specific growth rate, endogenous metabolism coefficient, Michaelis-Menten coefficient, yield and maintenance coefficient for glucose were derived and correlated the effect of the hydrogen ion concentration. Specific oxygen uptake rates were correlated with specific growth rates and absorption coefficients were shown to be a function of dilution rate independent of pH. Some data on cellulase biosynthesis were examined and correlated in terms of a maturation time model.", "contents": "Growth kinetics and cellulase biosynthesis in the continuous culture of Trichoderma viride. Continuous culture studies have been carried out growing Trichoderma viride QM 9123 in a 10 liter stirred fermentor on a medium containing commercial glucose as the carbon source. Experiments were carried out at 30 degrees C and at three controlled pH values of 2.5, 3.0, and 4.0 over a range of dilution rates from 0.01 to 0.11 hr-1. Steady-state values of cell, glucose, and cellulase concentration oxygen tension, and outlet gas oxygen partial pressure were recorded. Values of maximum specific growth rate, endogenous metabolism coefficient, Michaelis-Menten coefficient, yield and maintenance coefficient for glucose were derived and correlated the effect of the hydrogen ion concentration. Specific oxygen uptake rates were correlated with specific growth rates and absorption coefficients were shown to be a function of dilution rate independent of pH. Some data on cellulase biosynthesis were examined and correlated in terms of a maturation time model."}
{"id": "PMID:18234", "title": "[Tyrosine hydroxylase activation upon electric stimulation of isolated hypothalamic nerve endings in rats].", "content": "The effect of electrical stimulation on the membrane-bound tyrosine hydroxylasectivity of the rat hypothalamus synaptosomes was studied. The electrical stimulation caused an elevation of O2 consumption and the elevation of glycolysis indicating synaptosome excitation. The membrane-bound tyrosine hydroxylase activity increased under these conditions. The KM value for tyrosine decreased from 0.091 to 0.026 mM. Noradrenaline inhibition of the enzymatic activity diminished. It is assumed that the effect of depolarization on the catecholamine synthesis velocity in the nerve endings involves tyrosine hydroxylase modification.", "contents": "[Tyrosine hydroxylase activation upon electric stimulation of isolated hypothalamic nerve endings in rats]. The effect of electrical stimulation on the membrane-bound tyrosine hydroxylasectivity of the rat hypothalamus synaptosomes was studied. The electrical stimulation caused an elevation of O2 consumption and the elevation of glycolysis indicating synaptosome excitation. The membrane-bound tyrosine hydroxylase activity increased under these conditions. The KM value for tyrosine decreased from 0.091 to 0.026 mM. Noradrenaline inhibition of the enzymatic activity diminished. It is assumed that the effect of depolarization on the catecholamine synthesis velocity in the nerve endings involves tyrosine hydroxylase modification."}
{"id": "PMID:18235", "title": "[Regeneration of mammalial plantar skin].", "content": "Two sole tubers of rat's hind leg were excised together with the surrounding skin and one of the hind tubers of hind and fore legs in hedgehogs were excised without the surrounding skin. During healing the skin wounds in rats and hedgehogs new skin proved to form with the papillary layer typical of the sole skin. In hedgehogs the new skin covered the regenerated sole tuber; in rats the sole tubers failed to regenerate.", "contents": "[Regeneration of mammalial plantar skin]. Two sole tubers of rat's hind leg were excised together with the surrounding skin and one of the hind tubers of hind and fore legs in hedgehogs were excised without the surrounding skin. During healing the skin wounds in rats and hedgehogs new skin proved to form with the papillary layer typical of the sole skin. In hedgehogs the new skin covered the regenerated sole tuber; in rats the sole tubers failed to regenerate."}
{"id": "PMID:18236", "title": "[Ammonia formation in the brain during dying and in the recovery period following resuscitation].", "content": "Dynamics of some nitrogen metabolism indices in the brain of dogs during dying and post-resuscitation period was studied in experiments on dogs. Glutamine proved to serve as the main source of ammonium hydrate in the brain during dying and clinical death. In the reconstruction period after revival of the organism glutamine was converted into ammonium eliminator, and the main sources of ammoniogenesis were labile amide protein groups.", "contents": "[Ammonia formation in the brain during dying and in the recovery period following resuscitation]. Dynamics of some nitrogen metabolism indices in the brain of dogs during dying and post-resuscitation period was studied in experiments on dogs. Glutamine proved to serve as the main source of ammonium hydrate in the brain during dying and clinical death. In the reconstruction period after revival of the organism glutamine was converted into ammonium eliminator, and the main sources of ammoniogenesis were labile amide protein groups."}
{"id": "PMID:18237", "title": "[Demethylation of methindione].", "content": "Methindion demethylation was shown to occur in rats. This process proceeds with the participation of NADPH-dependent transport system of microsomal electrons. In experiments in vivo methindion demethylation coursed at a high rate and was accompanied by a partial loss of its anticonvulsive effects.", "contents": "[Demethylation of methindione]. Methindion demethylation was shown to occur in rats. This process proceeds with the participation of NADPH-dependent transport system of microsomal electrons. In experiments in vivo methindion demethylation coursed at a high rate and was accompanied by a partial loss of its anticonvulsive effects."}
{"id": "PMID:18238", "title": "[Inactivation of stem cells by allogenic lymphocytes: competition between T1- and T2-subpopulations].", "content": "Transplantation of the bone marrow cells with allogeneic T-lymphocytes to the irradiated hosts was accompanied by inactivation of the stem elements of the graft. The lymph node cells of T-mice (those deprived of B cells) were more active than the spleen cells of these mice. The stem cells inactivation was weakly expressed or absent in case of a combined acti-n of T-cells from the lymph nodes and the spleen.", "contents": "[Inactivation of stem cells by allogenic lymphocytes: competition between T1- and T2-subpopulations]. Transplantation of the bone marrow cells with allogeneic T-lymphocytes to the irradiated hosts was accompanied by inactivation of the stem elements of the graft. The lymph node cells of T-mice (those deprived of B cells) were more active than the spleen cells of these mice. The stem cells inactivation was weakly expressed or absent in case of a combined acti-n of T-cells from the lymph nodes and the spleen."}
{"id": "PMID:18239", "title": "Demonstration of hemopoietic stem cells in the peripheral blood of baboons by cross circulation.", "content": "Baboons were given 1200 R total body irradiation from two opposing 60Co sources. Three animals were given supportive therapy only and died, as expected, within 8 days of irradiation with profound marrow hypoplasia. Five baboons were cross-circulated with unirradiated partners and died within 14 days with evidence suggestive of graft-versus-host disease. Their marrows were repopulated with hemopoietic precursor cells, and three of the five had rises in peripheral white blood cell counts to more than 1500/cu mm before death. These results are compatible with the presence of hemopoietic stem cells in the peripheral blood of a nonhuman primate, the baboon.", "contents": "Demonstration of hemopoietic stem cells in the peripheral blood of baboons by cross circulation. Baboons were given 1200 R total body irradiation from two opposing 60Co sources. Three animals were given supportive therapy only and died, as expected, within 8 days of irradiation with profound marrow hypoplasia. Five baboons were cross-circulated with unirradiated partners and died within 14 days with evidence suggestive of graft-versus-host disease. Their marrows were repopulated with hemopoietic precursor cells, and three of the five had rises in peripheral white blood cell counts to more than 1500/cu mm before death. These results are compatible with the presence of hemopoietic stem cells in the peripheral blood of a nonhuman primate, the baboon."}
{"id": "PMID:18243", "title": "Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam.", "content": "1 Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid-brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid-brain region of rats subjected to benzodiazepine treatment.2 Chronic therapy with either of the two anti-anxiety agents enhanced the endogenous levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons-medulla, mid-brain and striatum.3 Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid-brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5-hydroxy-indoleacetic acid levels is not associated with enhanced deamination of 5-hydroxytryptamine.4 Discontinuation of treatment for 48 h significantly decreased the activity of mid-brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine-treated and normal rats. The concentrations of mid-brain tryptophan and 5-hydroxytryptamine were also reduced in various brain regions examined.5 Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5-hydroxyindoleacetic acid.6 The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5-hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine.", "contents": "Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam. 1 Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid-brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid-brain region of rats subjected to benzodiazepine treatment.2 Chronic therapy with either of the two anti-anxiety agents enhanced the endogenous levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons-medulla, mid-brain and striatum.3 Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid-brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5-hydroxy-indoleacetic acid levels is not associated with enhanced deamination of 5-hydroxytryptamine.4 Discontinuation of treatment for 48 h significantly decreased the activity of mid-brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine-treated and normal rats. The concentrations of mid-brain tryptophan and 5-hydroxytryptamine were also reduced in various brain regions examined.5 Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5-hydroxyindoleacetic acid.6 The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5-hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine."}
{"id": "PMID:18244", "title": "Responses of the cardiovascular system of the rat to alpha-and beta-adrenoceptor agonists.", "content": "1 The effects of intravenously infused phenylephrine and isoprenaline upon the cardiovascular system of the rat anaesthetized with pentobarbitone, have been investigated.2 Phenylephrine produces a dose-dependent rise in mean arterial blood pressure (MABP) that is due mainly to an increase in total peripheral vascular resistance (TPR), though at all doses tested cardiac output was invariably raised.3 The increase in cardiac output was due in each instance to an increase in stroke volume, heart rate being unchanged. This increase in cardiac output is probably brought about by effects of phenylephrine on the capacitance vessels rather than by an effect on the heart.4 Evidence is presented to show that the effects of phenylephrine are mediated largely by alpha-adrenoceptors, but that beta-adrenoceptors which affect TPR are also stimulated by the amine.5 Isoprenaline produces a dose-dependent fall in MABP that is due entirely to a fall in TPR since the cardiac output increases.6 Unlike phenylephrine, the increase in cardiac output obtained with isoprenaline was achieved by an increase in heart rate while stroke volume remained close to control values. It is contended that the augmented venous return required for the elevated cardiac output results in this case mainly from the isoprenaline-induced fall in TPR which enhances transfer of blood from arteries to the veins.7 Evidence is presented to show that the effects of isoprenaline are mediated mainly by beta-adrenoceptors.8 Under the present experimental conditions the adrenoceptor-mediated cardiovascular changes are little modified reflexly by the arterial baroreceptors.", "contents": "Responses of the cardiovascular system of the rat to alpha-and beta-adrenoceptor agonists. 1 The effects of intravenously infused phenylephrine and isoprenaline upon the cardiovascular system of the rat anaesthetized with pentobarbitone, have been investigated.2 Phenylephrine produces a dose-dependent rise in mean arterial blood pressure (MABP) that is due mainly to an increase in total peripheral vascular resistance (TPR), though at all doses tested cardiac output was invariably raised.3 The increase in cardiac output was due in each instance to an increase in stroke volume, heart rate being unchanged. This increase in cardiac output is probably brought about by effects of phenylephrine on the capacitance vessels rather than by an effect on the heart.4 Evidence is presented to show that the effects of phenylephrine are mediated largely by alpha-adrenoceptors, but that beta-adrenoceptors which affect TPR are also stimulated by the amine.5 Isoprenaline produces a dose-dependent fall in MABP that is due entirely to a fall in TPR since the cardiac output increases.6 Unlike phenylephrine, the increase in cardiac output obtained with isoprenaline was achieved by an increase in heart rate while stroke volume remained close to control values. It is contended that the augmented venous return required for the elevated cardiac output results in this case mainly from the isoprenaline-induced fall in TPR which enhances transfer of blood from arteries to the veins.7 Evidence is presented to show that the effects of isoprenaline are mediated mainly by beta-adrenoceptors.8 Under the present experimental conditions the adrenoceptor-mediated cardiovascular changes are little modified reflexly by the arterial baroreceptors."}
{"id": "PMID:18245", "title": "Responses of the cardiovascular system of the rat to noradrenaline infusions and their modification by adrenoceptor blocking agents.", "content": "1 The effects of noradrenaline upon the cardiovascular system of the rat, anaesthetized with pentobarbitone, have been investigated.2 Noradrenaline produces a dose-dependent increase in mean arterial blood pressure (MABP) which is due entirely to an increase in cardiac output; total peripheral vascular resistance (TPR) remains unchanged.3 Following beta-adrenoceptor blockade the pressor response to infused noradrenaline is enhanced and is now due mainly to an increase in TPR; the increment in cardiac output is reduced.4 After alpha-adrenoceptor blockade the pressor response is greatly reduced; the residual increase in MABP is due solely to an increase in cardiac output.5 After ganglion blockade resting cardiac output and TPR both fall, resulting in a reduction in MABP. The pressor response to noradrenaline is enhanced and is now due to increases in both TPR and in cardiac output.6 The cardiovascular response of the anaesthetized rat to noradrenaline can be explained in terms of classical alpha- and beta-adrenoceptor stimulation by the amine; the unusual form of the response may be due to an effective predominance of beta-adrenoceptor-mediated effects in this species.7 It is suggested that the failure of exogenous noradrenaline to produce a rise in TPR results from a balance between the alpha-adrenoceptor-mediated increase and beta-adrenoceptor-mediated decrease in this variable. However, this proposed balance is lost if resting vasoconstrictor tone is reduced by ganglion blockade.", "contents": "Responses of the cardiovascular system of the rat to noradrenaline infusions and their modification by adrenoceptor blocking agents. 1 The effects of noradrenaline upon the cardiovascular system of the rat, anaesthetized with pentobarbitone, have been investigated.2 Noradrenaline produces a dose-dependent increase in mean arterial blood pressure (MABP) which is due entirely to an increase in cardiac output; total peripheral vascular resistance (TPR) remains unchanged.3 Following beta-adrenoceptor blockade the pressor response to infused noradrenaline is enhanced and is now due mainly to an increase in TPR; the increment in cardiac output is reduced.4 After alpha-adrenoceptor blockade the pressor response is greatly reduced; the residual increase in MABP is due solely to an increase in cardiac output.5 After ganglion blockade resting cardiac output and TPR both fall, resulting in a reduction in MABP. The pressor response to noradrenaline is enhanced and is now due to increases in both TPR and in cardiac output.6 The cardiovascular response of the anaesthetized rat to noradrenaline can be explained in terms of classical alpha- and beta-adrenoceptor stimulation by the amine; the unusual form of the response may be due to an effective predominance of beta-adrenoceptor-mediated effects in this species.7 It is suggested that the failure of exogenous noradrenaline to produce a rise in TPR results from a balance between the alpha-adrenoceptor-mediated increase and beta-adrenoceptor-mediated decrease in this variable. However, this proposed balance is lost if resting vasoconstrictor tone is reduced by ganglion blockade."}
{"id": "PMID:18246", "title": "Development of nicotinic responses in the rat adrenal medulla and long-term effects of neonatal nicotine administration.", "content": "1. The development of nicotinic responses in the rat adrenal medulla was examined at various ages from 1 to 50 days of age by testing the ability of nicotine (10 mg/kg, s.c.) to deplete catecholamines and induce tyrosine hydroxylase. 2. Catecholamines were depleted 25% 3 h after injection of nicotine at all ages tested, but the degree of tyrosine hydroxylase induction 24 h after nicotine increased with age. 3. These data indicate that functional nicotinic receptors are present in the neonatal adrenal medulla before the development of functional splanchnic innervation, but that the development of the ability to induce tyrosine hydroxylase is not coupled directly to the development of secretory mechanisms. 4. The long-term effects of a single dose of nicotine (10 mg/kg, s.c.) administered to one day old rats were also examined. 5. After the short-term catecholamine depletion caused by nicotine, there were persistent elevations of catecholamines and tyrosine hydroxylase until 23 days of age; however, dopamine beta-hydroxylase remained elevated into young adulthood. 6. These data indicate that neonatal nicotine administration can produce long-term changes in adrenal catecholamine biosynthetic enzymes.", "contents": "Development of nicotinic responses in the rat adrenal medulla and long-term effects of neonatal nicotine administration. 1. The development of nicotinic responses in the rat adrenal medulla was examined at various ages from 1 to 50 days of age by testing the ability of nicotine (10 mg/kg, s.c.) to deplete catecholamines and induce tyrosine hydroxylase. 2. Catecholamines were depleted 25% 3 h after injection of nicotine at all ages tested, but the degree of tyrosine hydroxylase induction 24 h after nicotine increased with age. 3. These data indicate that functional nicotinic receptors are present in the neonatal adrenal medulla before the development of functional splanchnic innervation, but that the development of the ability to induce tyrosine hydroxylase is not coupled directly to the development of secretory mechanisms. 4. The long-term effects of a single dose of nicotine (10 mg/kg, s.c.) administered to one day old rats were also examined. 5. After the short-term catecholamine depletion caused by nicotine, there were persistent elevations of catecholamines and tyrosine hydroxylase until 23 days of age; however, dopamine beta-hydroxylase remained elevated into young adulthood. 6. These data indicate that neonatal nicotine administration can produce long-term changes in adrenal catecholamine biosynthetic enzymes."}
{"id": "PMID:18247", "title": "Central mechanism of vasopressin-induced changes in antidiuretic hormone release.", "content": "1. Intracerebroventricularly (i.c.v.) administered vasopressin (0.001-1.0 u) in dogs anaesthetized with chloralose produced adose-dependent increase in urine flow with a concomitant decrease in the levels of antidiuretic hormone (ADH) in jugular vein blood. 2. Higher doses of vasopressin (1.5-2.0 u, i.c.v) on the other hand had an antidiuretic effect and produced an increase in blood ADH level. 3. Pretreatment (i.c.v.) with a beta-adrenoceptor antagonist completely blocked the diuretic response of low doses of vasopressin (i.c.v.) but  did not influence the antidiuretic response obtained with high doses. 4. Repeated administration of vasopressin (1.0 u, i.c.v.) induced tachyphylaxis; central catecholamine depletion with tetrabenazine significantly inhibited the vasopressin-induced diuretic response. 5. It is concluded that intracerebroventricular vasopressin-induced changes in ADH secretion are mediated through the release of catecholamines in the central nervous system.", "contents": "Central mechanism of vasopressin-induced changes in antidiuretic hormone release. 1. Intracerebroventricularly (i.c.v.) administered vasopressin (0.001-1.0 u) in dogs anaesthetized with chloralose produced adose-dependent increase in urine flow with a concomitant decrease in the levels of antidiuretic hormone (ADH) in jugular vein blood. 2. Higher doses of vasopressin (1.5-2.0 u, i.c.v) on the other hand had an antidiuretic effect and produced an increase in blood ADH level. 3. Pretreatment (i.c.v.) with a beta-adrenoceptor antagonist completely blocked the diuretic response of low doses of vasopressin (i.c.v.) but  did not influence the antidiuretic response obtained with high doses. 4. Repeated administration of vasopressin (1.0 u, i.c.v.) induced tachyphylaxis; central catecholamine depletion with tetrabenazine significantly inhibited the vasopressin-induced diuretic response. 5. It is concluded that intracerebroventricular vasopressin-induced changes in ADH secretion are mediated through the release of catecholamines in the central nervous system."}
{"id": "PMID:18248", "title": "Selectivity of blocking agents for pre-and postsynaptic alpha-adrenoceptors.", "content": "1. Low frequency (0.1 Hz) electrical stimulation of the rat isolated vas deferens produced regular contractions that were inhibited by low concentrations of clonidine. 2. The inhibition of the vas deferens produced by clonidine was presynaptic in origin and involved alpha-adrenoceptors. 3. Presynaptic alpha-adrenoceptor antagonist activity was assessed by studying the effects of increasing concentrations of the antagonists on cumulative clonidine dose-response curves on the stimulated vas deferens. 4. Postsynaptic alpha-adrenoceptor antagonist activity was assessed by comparison of control cumulative noradrenaline dose-response curves with those in the presence of increasing concentrations of antagonists in the rat anococcygeus muscle. 5. The results indicate that yohimbine and phentolamine are more potent in blocking presynaptic than postsynaptic alpha-adrenoceptors. Phenoxybenzamine and prazosin block postsynaptic alpha-adrenoceptors preferentially. 6. The findings support the view that presynaptic and postsynaptic alpha-adrenoceptors differ in their sensitivity to alpha-adrenoceptor antagonists.", "contents": "Selectivity of blocking agents for pre-and postsynaptic alpha-adrenoceptors. 1. Low frequency (0.1 Hz) electrical stimulation of the rat isolated vas deferens produced regular contractions that were inhibited by low concentrations of clonidine. 2. The inhibition of the vas deferens produced by clonidine was presynaptic in origin and involved alpha-adrenoceptors. 3. Presynaptic alpha-adrenoceptor antagonist activity was assessed by studying the effects of increasing concentrations of the antagonists on cumulative clonidine dose-response curves on the stimulated vas deferens. 4. Postsynaptic alpha-adrenoceptor antagonist activity was assessed by comparison of control cumulative noradrenaline dose-response curves with those in the presence of increasing concentrations of antagonists in the rat anococcygeus muscle. 5. The results indicate that yohimbine and phentolamine are more potent in blocking presynaptic than postsynaptic alpha-adrenoceptors. Phenoxybenzamine and prazosin block postsynaptic alpha-adrenoceptors preferentially. 6. The findings support the view that presynaptic and postsynaptic alpha-adrenoceptors differ in their sensitivity to alpha-adrenoceptor antagonists."}
{"id": "PMID:18249", "title": "The use of functional antagonism to determine whether beta-adrenoceptor agonists must have a lower efficacy than isoprenaline to be trachea-atria selective in vitro in guinea-pigs.", "content": "1 The relative efficacies of three trachea-atria selective beta-adrenoceptor agonists, fenoterol, Me 506 and Me 454, compared to isoprenaline, were determined on both trachea and atria of guinea-pigs. 2 On tracheal preparations the beta-adrenoceptor agonists were used as functional antagonists of carbachol and a comparison of the maximum shifts in the carbachol concentration-response line produced by each of the beta-adrenoceptor agonists provided a comparison of their efficacies. 3 On atrial preparations carbachol was used as a functional antagonist of the beta-adrenoceptor agonists and comparison of the maximum responses to the beta-adrenoceptor agonists in the presence of carbachol provided a comparison of their efficacies. 4 On trachea and atria the order of efficacy of the compounds was Me454 greater than Me506 greater than or equal to isoprenaline=fenoterol. 5. The results indicated that high efficacy in a non-catechol beta-adrenoceptor agonist is possible provided there is a favourable N-substituent group. 6 Since Me 454, Me 506 and fenoterol, which are trachea-atria selective, have effficacies equal to or greater than that of isoprenaline, which is non-selective, it is concluded that low efficacy in a compound is not essential for it to show trachea-atria selectivity in vitro in guinea-pigs.", "contents": "The use of functional antagonism to determine whether beta-adrenoceptor agonists must have a lower efficacy than isoprenaline to be trachea-atria selective in vitro in guinea-pigs. 1 The relative efficacies of three trachea-atria selective beta-adrenoceptor agonists, fenoterol, Me 506 and Me 454, compared to isoprenaline, were determined on both trachea and atria of guinea-pigs. 2 On tracheal preparations the beta-adrenoceptor agonists were used as functional antagonists of carbachol and a comparison of the maximum shifts in the carbachol concentration-response line produced by each of the beta-adrenoceptor agonists provided a comparison of their efficacies. 3 On atrial preparations carbachol was used as a functional antagonist of the beta-adrenoceptor agonists and comparison of the maximum responses to the beta-adrenoceptor agonists in the presence of carbachol provided a comparison of their efficacies. 4 On trachea and atria the order of efficacy of the compounds was Me454 greater than Me506 greater than or equal to isoprenaline=fenoterol. 5. The results indicated that high efficacy in a non-catechol beta-adrenoceptor agonist is possible provided there is a favourable N-substituent group. 6 Since Me 454, Me 506 and fenoterol, which are trachea-atria selective, have effficacies equal to or greater than that of isoprenaline, which is non-selective, it is concluded that low efficacy in a compound is not essential for it to show trachea-atria selectivity in vitro in guinea-pigs."}
{"id": "PMID:18257", "title": "Subcellular distribution of glutamyltransferase activities in embryonic cerebral hemispheres.", "content": "Glutamyltransferase (GT) activities were examined in cell groups from embryonic cerebral hemispheres. During normal development, GT activities were highest in a mixed population of small neurons and non-neuronal cells (small cell group). In culture, in response to hydrocortisone, activities exceeded normal levels only in this small cell group. In view of these findings, the small cell population was used to study the subcellular distribution of the enzyme. At the subcellular level, GT activities in the small cell group were distributed differentially but increased generally during normal development. In vitro, hydrocortisone promoted a precocious increase in GT activity, under experimental conditions regarded as optimum, only in the subcellular fraction characterized by synaptic endings.", "contents": "Subcellular distribution of glutamyltransferase activities in embryonic cerebral hemispheres. Glutamyltransferase (GT) activities were examined in cell groups from embryonic cerebral hemispheres. During normal development, GT activities were highest in a mixed population of small neurons and non-neuronal cells (small cell group). In culture, in response to hydrocortisone, activities exceeded normal levels only in this small cell group. In view of these findings, the small cell population was used to study the subcellular distribution of the enzyme. At the subcellular level, GT activities in the small cell group were distributed differentially but increased generally during normal development. In vitro, hydrocortisone promoted a precocious increase in GT activity, under experimental conditions regarded as optimum, only in the subcellular fraction characterized by synaptic endings."}
{"id": "PMID:18259", "title": "Mnoaminergic reinnervation of the transected spinal cord by homologous fetal brain grafts.", "content": "It was shown that immature noradrenaline (NA) containing cells from locus coeruleus and 5-hydroxytryptamine (5-HT) containing cells from the raph\u00e9 nuclei could survive homologous transplantation to adult spinal cords that were adrenergically denervated by a transverse lesion. Fully viable transplants were found at all postoperative time studied (0.5-4 months) and both NA and 5-HT cell bodies were found to produce a network of nerve terminals in the gray matter and axons in the white matter that reached cranially and caudally at least 10 mm from the cell bodies. The nerve fibers had a normal varicose appearance. It was concluded that NA and 5-HT axons can grow in adult lesioned white matter.", "contents": "Mnoaminergic reinnervation of the transected spinal cord by homologous fetal brain grafts. It was shown that immature noradrenaline (NA) containing cells from locus coeruleus and 5-hydroxytryptamine (5-HT) containing cells from the raph\u00e9 nuclei could survive homologous transplantation to adult spinal cords that were adrenergically denervated by a transverse lesion. Fully viable transplants were found at all postoperative time studied (0.5-4 months) and both NA and 5-HT cell bodies were found to produce a network of nerve terminals in the gray matter and axons in the white matter that reached cranially and caudally at least 10 mm from the cell bodies. The nerve fibers had a normal varicose appearance. It was concluded that NA and 5-HT axons can grow in adult lesioned white matter."}
{"id": "PMID:18265", "title": "Determination of the preferred tautomeric form histamine by 13C nmr spectroscopy.", "content": "The pH-dependent 13C chemical shifts for histamine indicate an approximate 4: 1 preference for the N-H tautomer of the imidazole ring, similar to that previously deduced for L-histidine. It is concluded that the 13C chemical shift method is a complimentary technique to the method of determining tautomer preference from pK values. Factors determining the tautomer preference in histamine and L-histidine are discussed.", "contents": "Determination of the preferred tautomeric form histamine by 13C nmr spectroscopy. The pH-dependent 13C chemical shifts for histamine indicate an approximate 4: 1 preference for the N-H tautomer of the imidazole ring, similar to that previously deduced for L-histidine. It is concluded that the 13C chemical shift method is a complimentary technique to the method of determining tautomer preference from pK values. Factors determining the tautomer preference in histamine and L-histidine are discussed."}
{"id": "PMID:18266", "title": "Effect of metabolites on epsilon-N-hydroxylysine formation in cell-free extracts of Aerobacter aerogenes 62-1.", "content": "The conversion of L-lysine to its corresponding epsilon-N-hydroxy derivative has been achieved for the first time by cell-free extracts of Aerobacter aerogenes 62-1. Partial fractionation by differential centrifugation (at 12 000 X g) revealed that both supernatant and pellet are essential for maximum enzymatic activity. The omega-N-hydroxylase (EC 1.14.99) was found to function optimally at pH 7-7.5 and exhibited an apparent Km of about 75 muM for L-lysine. L(+)-Lactate or DL-lactate and pyruvate greatly stimulate the omega-N-hydroxylase activity. The system is strongly inhibited by arsenite and sulfite.", "contents": "Effect of metabolites on epsilon-N-hydroxylysine formation in cell-free extracts of Aerobacter aerogenes 62-1. The conversion of L-lysine to its corresponding epsilon-N-hydroxy derivative has been achieved for the first time by cell-free extracts of Aerobacter aerogenes 62-1. Partial fractionation by differential centrifugation (at 12 000 X g) revealed that both supernatant and pellet are essential for maximum enzymatic activity. The omega-N-hydroxylase (EC 1.14.99) was found to function optimally at pH 7-7.5 and exhibited an apparent Km of about 75 muM for L-lysine. L(+)-Lactate or DL-lactate and pyruvate greatly stimulate the omega-N-hydroxylase activity. The system is strongly inhibited by arsenite and sulfite."}
{"id": "PMID:18267", "title": "Studies related to antitumor antibiotics. Part IX. Reactions of carzinophillin with DNA assayed by ethidium fluorescence.", "content": "The reactions of the antitumor antibiotic carzinophillin (CZ) with native DNAs and synthetic polynucleotides have been examined by an ethidium fluorescence assay. CZ rapidly produces covalent linkage of the complementary strands of a variety of DNAs without activation. This process is accompanied by extensive alkylation, as detected by reduced fluorescence due to destruction of potential intercalation sites for ethidium. These processes which occur without loss of purine or pyrimidine bases show a preference for bonding to guanine groups (but not at the N-7 position). Examination of the reversibility of the cross-links suggests they involve one 'permanent' link to guanine and a second weaker linkage, possibly to a cytosine residue. Both cross-linking and alkylation show strong pH dependence and are favored at lower pH, suggesting that reactive sites on the antibiotic are basic. The addition of intercalating agents to DNA before treatment with CZ inhibits the cross-linking.", "contents": "Studies related to antitumor antibiotics. Part IX. Reactions of carzinophillin with DNA assayed by ethidium fluorescence. The reactions of the antitumor antibiotic carzinophillin (CZ) with native DNAs and synthetic polynucleotides have been examined by an ethidium fluorescence assay. CZ rapidly produces covalent linkage of the complementary strands of a variety of DNAs without activation. This process is accompanied by extensive alkylation, as detected by reduced fluorescence due to destruction of potential intercalation sites for ethidium. These processes which occur without loss of purine or pyrimidine bases show a preference for bonding to guanine groups (but not at the N-7 position). Examination of the reversibility of the cross-links suggests they involve one 'permanent' link to guanine and a second weaker linkage, possibly to a cytosine residue. Both cross-linking and alkylation show strong pH dependence and are favored at lower pH, suggesting that reactive sites on the antibiotic are basic. The addition of intercalating agents to DNA before treatment with CZ inhibits the cross-linking."}
{"id": "PMID:18268", "title": "Characteristics of potassium ion transport in pea cotyledon mitochondria isolated by a zonal technique.", "content": "Methodology was developed for measurement of K+ transport in pea cotyledon mitochondria isolated by zonal centrifugation. The valinomycin-mediated transport process required respiratory energy from Krebs cycle intermediates and was completely reversible in the absence of oxygen. The rate and extent of uptake were dependent on the presence of proton-conducting anions (with acetate plus phosphate being most effective), well-coupled mitochondria, and on the K+ concentration.", "contents": "Characteristics of potassium ion transport in pea cotyledon mitochondria isolated by a zonal technique. Methodology was developed for measurement of K+ transport in pea cotyledon mitochondria isolated by zonal centrifugation. The valinomycin-mediated transport process required respiratory energy from Krebs cycle intermediates and was completely reversible in the absence of oxygen. The rate and extent of uptake were dependent on the presence of proton-conducting anions (with acetate plus phosphate being most effective), well-coupled mitochondria, and on the K+ concentration."}
{"id": "PMID:18270", "title": "Lithium suppresses elevated behavioural activity and brain catecholamines in developing hyperthyroid rats.", "content": "Neonatal hyperthyroidism in rats induced by daily administration of L-triiodothyronine for 30 days since birth resulted in a significant rise in mobility and the metabolism of brain norepinephrine and dopamine. Whereas administration of lithium carbonate (60 mg/kg ip) to normal rats for 6 days produced no effect on spontaneous locomotor activity and increased the synthesis and possibly release of this monoamine in several brain regions, this antimanic drug antagonized the L-triiodothyronine-stimulated increases in mobility as well as norepinephrine and dopamine metabolism of hypothalamus, midbrain, striatum, and cerebral cortex. Furthermore, lithium treatment restored the activity of catechol-O-methyl transferase (EC 2.1.1.6) in young hyperthyroid rats to virtually normal limits. Our data suggest that antiphasic or damping effects of lithium upon mood swings is controlled, at least in part, by catecholaminergic systems in the brain. The interrelationship between brain catecholamines and thyroid hormones seems to be important to our understanding of the action of lithium in affective illness.", "contents": "Lithium suppresses elevated behavioural activity and brain catecholamines in developing hyperthyroid rats. Neonatal hyperthyroidism in rats induced by daily administration of L-triiodothyronine for 30 days since birth resulted in a significant rise in mobility and the metabolism of brain norepinephrine and dopamine. Whereas administration of lithium carbonate (60 mg/kg ip) to normal rats for 6 days produced no effect on spontaneous locomotor activity and increased the synthesis and possibly release of this monoamine in several brain regions, this antimanic drug antagonized the L-triiodothyronine-stimulated increases in mobility as well as norepinephrine and dopamine metabolism of hypothalamus, midbrain, striatum, and cerebral cortex. Furthermore, lithium treatment restored the activity of catechol-O-methyl transferase (EC 2.1.1.6) in young hyperthyroid rats to virtually normal limits. Our data suggest that antiphasic or damping effects of lithium upon mood swings is controlled, at least in part, by catecholaminergic systems in the brain. The interrelationship between brain catecholamines and thyroid hormones seems to be important to our understanding of the action of lithium in affective illness."}
{"id": "PMID:18274", "title": "The tricarboxylic and acid pathway in Desulfovibrio.", "content": "Strains of two species of Desulfovibrio were examined for enzymes of the tricarboxylic acid cycle and related pathways. Pyruvate carboxylase (EC6.4.1.1) is present, and alpha-ketoglutarate is formed via the tricarboxylic acids. Glutamate, but not succinyl-CoA, arises from alpha-ketoglutarate. A pathway exists from pyruvate by malic enzyme (EC 1.1.1.39) activity to malate, then fumarate and succinate, again with no evidence of succinyl-CoA formation. The enzymes concerned with metabolism of these dicarboxylic acids show greater activity in the strains that can grow by fumarate dismutation. Glutamate (or glutamine), alpha-ketoglutarate, and yeast extract repress the enzymes that metabolize the tricarboxylic acids. There appears to be no glyoxylate cycle in Desulfovibrio vulgaris or D. desulfuricans.", "contents": "The tricarboxylic and acid pathway in Desulfovibrio. Strains of two species of Desulfovibrio were examined for enzymes of the tricarboxylic acid cycle and related pathways. Pyruvate carboxylase (EC6.4.1.1) is present, and alpha-ketoglutarate is formed via the tricarboxylic acids. Glutamate, but not succinyl-CoA, arises from alpha-ketoglutarate. A pathway exists from pyruvate by malic enzyme (EC 1.1.1.39) activity to malate, then fumarate and succinate, again with no evidence of succinyl-CoA formation. The enzymes concerned with metabolism of these dicarboxylic acids show greater activity in the strains that can grow by fumarate dismutation. Glutamate (or glutamine), alpha-ketoglutarate, and yeast extract repress the enzymes that metabolize the tricarboxylic acids. There appears to be no glyoxylate cycle in Desulfovibrio vulgaris or D. desulfuricans."}
{"id": "PMID:18277", "title": "A case of homosexuality treated by in vivo desensitization and assertive training.", "content": "Sexual deviation is not a unitary condition, amenable to a single treatment approach. Deviant sexual arousal has been overemphasized while inadequate attention has been given to associated behavioural problems such as deficient heterosexual arousal, deficient heterosexual skills and gender role deviation. A client with homosexual arousal and requesting aversion therapy was treated successfully and rapidly using in vivo desensitization and assertive training. The treatment is described and the importance of the behavioural analysis in directing the course of therapy is stressed.", "contents": "A case of homosexuality treated by in vivo desensitization and assertive training. Sexual deviation is not a unitary condition, amenable to a single treatment approach. Deviant sexual arousal has been overemphasized while inadequate attention has been given to associated behavioural problems such as deficient heterosexual arousal, deficient heterosexual skills and gender role deviation. A client with homosexual arousal and requesting aversion therapy was treated successfully and rapidly using in vivo desensitization and assertive training. The treatment is described and the importance of the behavioural analysis in directing the course of therapy is stressed."}
{"id": "PMID:18278", "title": "Metabolic response to total parenteral nutrition in cancer patients.", "content": "In order to evaluate the metabolic response of nutritionally deprived cancer patients to parenteral nutrition, metabolic parameters including glucose turnover, oxidation, and Cori cycle activity were measured in eight patients before and during short-term (5 to 10 days) i.v. nutrition, with solutions containing amino acids and hypertonic glucose. Before parenteral nutrition, five patients had essentially normal glucose turnover, oxidation, and Cori cycle activity, whereas three patients had moderately increased glucose turnover and markedly increased Cori cycle activity. In response to parenteral nutrition, plasma glucose, insulin, and venous lactate concentration increased and free fatty acid decreased. The percentage of respiratory CO2 from glucose oxidation and the rate of oxidation increased. CO2 production increased, whereas O2 consumption was essentially unchanged. Respiratory quotient rose to greater than 1.0. Endogenous glucose production and high basal Cori cycle activity were decreased. Total parenteral nutrition was judged clinically beneficial in five patients, whereas one patient was unchanged. Deleterious responses, including moderate lactic acidemia, occurred in two of three patients with elevated basal Cori cycle activity.", "contents": "Metabolic response to total parenteral nutrition in cancer patients. In order to evaluate the metabolic response of nutritionally deprived cancer patients to parenteral nutrition, metabolic parameters including glucose turnover, oxidation, and Cori cycle activity were measured in eight patients before and during short-term (5 to 10 days) i.v. nutrition, with solutions containing amino acids and hypertonic glucose. Before parenteral nutrition, five patients had essentially normal glucose turnover, oxidation, and Cori cycle activity, whereas three patients had moderately increased glucose turnover and markedly increased Cori cycle activity. In response to parenteral nutrition, plasma glucose, insulin, and venous lactate concentration increased and free fatty acid decreased. The percentage of respiratory CO2 from glucose oxidation and the rate of oxidation increased. CO2 production increased, whereas O2 consumption was essentially unchanged. Respiratory quotient rose to greater than 1.0. Endogenous glucose production and high basal Cori cycle activity were decreased. Total parenteral nutrition was judged clinically beneficial in five patients, whereas one patient was unchanged. Deleterious responses, including moderate lactic acidemia, occurred in two of three patients with elevated basal Cori cycle activity."}
{"id": "PMID:18280", "title": "A radioimmunoassay for 1-beta-D-arabinofuranosyluracil with reference to cross-reactivity of 1-beta-D-arabinofuranosylcytosine with an antibody.", "content": "Antibodies directed against 1-beta-D-arabinofuranosyluracil have been produced in rabbits by immunization with a conjugate of 1-(5-O-succinyl-beta-D-arabinofuranosyl)uracil with human serum albumin. Two of four antibodies so obtained showed high specificity for 1-beta-D-arabinofuranosyluracil and allowed the development of a sensitive and reliable radioimmunoassay for this substrate. On the other hand, one antibody had a high affinity for 1-beta-D-arabinofuranosylcytosine. The binding of 1-beta-D-arabinofuranosylcytosine to this antibody was practically constant between pH 5.2 and 9.0, whereas 1-beta-D-arabinofuranosyluracil binding was affected drastically by pH. The pH-binding profile for 1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosyluracil was reminiscent of the specificity of ara-C-specific antibodies, which we previously obtained after immunization of rabbits with 1-(5-O-succinyl-beta-D-arabinofuranosyl)cytosine as a hapten.", "contents": "A radioimmunoassay for 1-beta-D-arabinofuranosyluracil with reference to cross-reactivity of 1-beta-D-arabinofuranosylcytosine with an antibody. Antibodies directed against 1-beta-D-arabinofuranosyluracil have been produced in rabbits by immunization with a conjugate of 1-(5-O-succinyl-beta-D-arabinofuranosyl)uracil with human serum albumin. Two of four antibodies so obtained showed high specificity for 1-beta-D-arabinofuranosyluracil and allowed the development of a sensitive and reliable radioimmunoassay for this substrate. On the other hand, one antibody had a high affinity for 1-beta-D-arabinofuranosylcytosine. The binding of 1-beta-D-arabinofuranosylcytosine to this antibody was practically constant between pH 5.2 and 9.0, whereas 1-beta-D-arabinofuranosyluracil binding was affected drastically by pH. The pH-binding profile for 1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosyluracil was reminiscent of the specificity of ara-C-specific antibodies, which we previously obtained after immunization of rabbits with 1-(5-O-succinyl-beta-D-arabinofuranosyl)cytosine as a hapten."}
{"id": "PMID:18281", "title": "Formation of methylhydrazine from acetaldehyde N-methyl-N-formylhydrazone, a component of Gyromitra esculenta.", "content": "Gyromitrin, acetaldehyde N-methyl-N-formylhydrazone, is a toxin present in edible wild mushroom Gyromitra esculenta. At 37 degrees under different acidic conditions (pH 1 to 3), mimicking the milieu of human stomach, gyromitrin is converted to methylhydrazine, a known tumor inducer in mice and hamsters, through an intermediate, N-methyl-N-formylhydrazine. In addition, methylhydrazine is formed in the mouse stomach after p.o. administration of gyromitrin. These findings imply that consumption of G. esculenta could present a carcinogenic, as well as an acutely toxic, health hazard.", "contents": "Formation of methylhydrazine from acetaldehyde N-methyl-N-formylhydrazone, a component of Gyromitra esculenta. Gyromitrin, acetaldehyde N-methyl-N-formylhydrazone, is a toxin present in edible wild mushroom Gyromitra esculenta. At 37 degrees under different acidic conditions (pH 1 to 3), mimicking the milieu of human stomach, gyromitrin is converted to methylhydrazine, a known tumor inducer in mice and hamsters, through an intermediate, N-methyl-N-formylhydrazine. In addition, methylhydrazine is formed in the mouse stomach after p.o. administration of gyromitrin. These findings imply that consumption of G. esculenta could present a carcinogenic, as well as an acutely toxic, health hazard."}
{"id": "PMID:18282", "title": "Weekly methotrexate-calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin's lymphoma.", "content": "Urinary alkalinization with oral sodium bicarbonate has decreased the incidence of acute nephrotoxicity and subsequent myelotoxicity in 18 adults receiving high-dose methotrexate with calcium leucovorin rescue (MTX-LCV) weekly in doses of 1-7.5 g/m2. Close monitoring of 24-hour serum creatinine and MTX levels can predict patients at risk for serious toxicity. By a prompt (24-36 hours) increase in the LCV dose rate, hematologic and biochemical evidence of myelosuppression has been prevented. Kinetic parameters in serum and lumbar cerebrospinal fluid (CSF) were studied in two patients following iv injection of 3 and 7.5 g/m2 respectively. Lumbar CSF MTX concentrations greater than 1 muM are achieved. The half-life of MTX in the CSF (11.95 hours) is twice as long as the serum half-life. In the presence of carcinomatous meningitis, further delay in the clearance of MTX from the CSF was seen. With weekly MTX-LCV, there have been four objective responses in six patients with non-Hodgkin's lymphoma in CNS relapse, including complete regression in two. It is suggested that therapeutic concentrations can be achieved in the central nervous system following MTX-LCV.", "contents": "Weekly methotrexate-calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin's lymphoma. Urinary alkalinization with oral sodium bicarbonate has decreased the incidence of acute nephrotoxicity and subsequent myelotoxicity in 18 adults receiving high-dose methotrexate with calcium leucovorin rescue (MTX-LCV) weekly in doses of 1-7.5 g/m2. Close monitoring of 24-hour serum creatinine and MTX levels can predict patients at risk for serious toxicity. By a prompt (24-36 hours) increase in the LCV dose rate, hematologic and biochemical evidence of myelosuppression has been prevented. Kinetic parameters in serum and lumbar cerebrospinal fluid (CSF) were studied in two patients following iv injection of 3 and 7.5 g/m2 respectively. Lumbar CSF MTX concentrations greater than 1 muM are achieved. The half-life of MTX in the CSF (11.95 hours) is twice as long as the serum half-life. In the presence of carcinomatous meningitis, further delay in the clearance of MTX from the CSF was seen. With weekly MTX-LCV, there have been four objective responses in six patients with non-Hodgkin's lymphoma in CNS relapse, including complete regression in two. It is suggested that therapeutic concentrations can be achieved in the central nervous system following MTX-LCV."}
{"id": "PMID:18283", "title": "Binding of alkyl 1-thio-beta-D-galactopyranosides to beta-D-galactosidase from E. coli.", "content": "The binding of a series of alkyl 1-thio-beta-D-galactopyranosides to beta-D-galactosidase from E. coli has been investigated. The inhibition constants were compared to the partition coefficients for the transfer of these substrate-analogues from water to 1-octanol. The relationships between the observed binding-constants and the partition coefficients indicate that part of the aglycon group binds to a hydrophobic area that is limited in relation to the length of hydrocarbon chain that can be accomodated. Outside this area, the hydrocarbon chain is only partially desolvated. The main driving-force  for binding of the aglycon group is the increase in entropy resulting from the return of water molecules from the more-organized layer around the solute molecule to the bulk-water phase.", "contents": "Binding of alkyl 1-thio-beta-D-galactopyranosides to beta-D-galactosidase from E. coli. The binding of a series of alkyl 1-thio-beta-D-galactopyranosides to beta-D-galactosidase from E. coli has been investigated. The inhibition constants were compared to the partition coefficients for the transfer of these substrate-analogues from water to 1-octanol. The relationships between the observed binding-constants and the partition coefficients indicate that part of the aglycon group binds to a hydrophobic area that is limited in relation to the length of hydrocarbon chain that can be accomodated. Outside this area, the hydrocarbon chain is only partially desolvated. The main driving-force  for binding of the aglycon group is the increase in entropy resulting from the return of water molecules from the more-organized layer around the solute molecule to the bulk-water phase."}
{"id": "PMID:18287", "title": "Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics.", "content": "Allograft rejection of fetal intestine and graft-versus-host (GvH) disease have been used to study the effects of cell-mediated immune reactions on epithelial cell kinetics in mouse small intestine. In heterotopically transplanted isografts the cell production rate per crypt was similar to that in normally sited small intestine of the same age. However there was a six-fold increase in the rate of cell production per crypt during allograft rejection and a three-fold increase during GvH disease. Furthermore animals with GvH disease developed villous atrophy and had fewer crypts per villus that littermate controls. At the age of 19 days cell production per villus per hour was 97-5 in animals with GvH disease compared with 54-6 in controls. These results indicate that the pathological entity of 'partial villous atrophy' evolves in two distinct phases. Phase 1, a state of increased cell turnover with crypt hyperplasia but villi of normal length precedes the development of Phase 2, true villous atrophy.", "contents": "Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics. Allograft rejection of fetal intestine and graft-versus-host (GvH) disease have been used to study the effects of cell-mediated immune reactions on epithelial cell kinetics in mouse small intestine. In heterotopically transplanted isografts the cell production rate per crypt was similar to that in normally sited small intestine of the same age. However there was a six-fold increase in the rate of cell production per crypt during allograft rejection and a three-fold increase during GvH disease. Furthermore animals with GvH disease developed villous atrophy and had fewer crypts per villus that littermate controls. At the age of 19 days cell production per villus per hour was 97-5 in animals with GvH disease compared with 54-6 in controls. These results indicate that the pathological entity of 'partial villous atrophy' evolves in two distinct phases. Phase 1, a state of increased cell turnover with crypt hyperplasia but villi of normal length precedes the development of Phase 2, true villous atrophy."}
{"id": "PMID:18288", "title": "The development of membrane specializations in the receptor-bipolar-horizontal cell synapse of the chick embryo retina. A freeze-fracture study.", "content": "Retinae of chick embryos and chicks one to six weeks after hatching were examined in ultrathin sections and in freeze-etch specimens. The development of the synaptic contacts between receptor cells and bipolar cells starts at the end of the second week of incubation with the enclosure of the dendritic prolongations, invaginating receptor terminals accompanied by the appearance of electron dense material at the synaptic contact sites. Subsequently receptor terminals become filled with synaptic vesicles which surround the synaptic lamellae that appear on the 16th day of incubation. The application of the freeze-fracture technique demonstrates that the differentiation of the synaptic membranes continues into the first week post hatching. E-fracture faces of the presynaptic membranes are characterized by crater-like structures, called synaptopores. Their number is rather small during incubation and increases after hatching. In the P-fracture faces of the dendrites, which are enclosed by the receptor terminals, small particle aggregations appear on the 16th day of incubation. These small particle clusters increase by the apposition of further particles which become arranged in lines and bring out a lattice-like aspect. This arrangement of particles in the inner part of the cell membrane is the morphological expression of the maturation process. The significance of these aggregations as a postsynaptic receptor for neurotransmitters in excitatory cells is discussed.", "contents": "The development of membrane specializations in the receptor-bipolar-horizontal cell synapse of the chick embryo retina. A freeze-fracture study. Retinae of chick embryos and chicks one to six weeks after hatching were examined in ultrathin sections and in freeze-etch specimens. The development of the synaptic contacts between receptor cells and bipolar cells starts at the end of the second week of incubation with the enclosure of the dendritic prolongations, invaginating receptor terminals accompanied by the appearance of electron dense material at the synaptic contact sites. Subsequently receptor terminals become filled with synaptic vesicles which surround the synaptic lamellae that appear on the 16th day of incubation. The application of the freeze-fracture technique demonstrates that the differentiation of the synaptic membranes continues into the first week post hatching. E-fracture faces of the presynaptic membranes are characterized by crater-like structures, called synaptopores. Their number is rather small during incubation and increases after hatching. In the P-fracture faces of the dendrites, which are enclosed by the receptor terminals, small particle aggregations appear on the 16th day of incubation. These small particle clusters increase by the apposition of further particles which become arranged in lines and bring out a lattice-like aspect. This arrangement of particles in the inner part of the cell membrane is the morphological expression of the maturation process. The significance of these aggregations as a postsynaptic receptor for neurotransmitters in excitatory cells is discussed."}
{"id": "PMID:18289", "title": "Fine structure of the adhesive pads of Gonionemus vertens.", "content": "The adhesive pads of Gonionemus vertens, located near the distal end of each tentacle, consist of a layer of columnar glandulomuscular cells surrounded by a collar of microfilament containing epithelial cells. The glandulomuscular cells contain dense secretory rods, microtubules, rough endoplasmic reticulum, Golgi elements and myonemes. Axons located between the basal portions of the glandulomuscular cells form synapses with the glandulomuscular cells. The roles of these various cell organelles in adhesion and detachment process are discussed.", "contents": "Fine structure of the adhesive pads of Gonionemus vertens. The adhesive pads of Gonionemus vertens, located near the distal end of each tentacle, consist of a layer of columnar glandulomuscular cells surrounded by a collar of microfilament containing epithelial cells. The glandulomuscular cells contain dense secretory rods, microtubules, rough endoplasmic reticulum, Golgi elements and myonemes. Axons located between the basal portions of the glandulomuscular cells form synapses with the glandulomuscular cells. The roles of these various cell organelles in adhesion and detachment process are discussed."}
{"id": "PMID:18291", "title": "Adduct formation between the carcinogen N-acetoxy-2-acetylaminofluorene and synthetic polydeoxyribonucleotides.", "content": "The chemical carcinogen N-acetoxy-2-acetylaminofluorene (NA-AAF) was reacted with poly(dG-dC) - poly(dG-dC); poly dG - poly dC; poly(dA-dT) - poly (dA-dT); and poly dA - poly dT under a variety of conditions. Poly (dG-homo GC polymer and 10--20 more reactive the A + T polymers. Lowering the ionic strength increased the extent of reaction, while pH change (8.9 vs. 5.5) had only a small effect. If ionic strength was adjusted so that the two guanine-containing polymers showed equal thermal stability (as judged by Tm) then the alternating copolymer was 7 times as reactive as the homopolymer. In aggreement with previous investigators, the major product was found to be 8-(N-2-fluorenylacetamido) deoxyguanosine.", "contents": "Adduct formation between the carcinogen N-acetoxy-2-acetylaminofluorene and synthetic polydeoxyribonucleotides. The chemical carcinogen N-acetoxy-2-acetylaminofluorene (NA-AAF) was reacted with poly(dG-dC) - poly(dG-dC); poly dG - poly dC; poly(dA-dT) - poly (dA-dT); and poly dA - poly dT under a variety of conditions. Poly (dG-homo GC polymer and 10--20 more reactive the A + T polymers. Lowering the ionic strength increased the extent of reaction, while pH change (8.9 vs. 5.5) had only a small effect. If ionic strength was adjusted so that the two guanine-containing polymers showed equal thermal stability (as judged by Tm) then the alternating copolymer was 7 times as reactive as the homopolymer. In aggreement with previous investigators, the major product was found to be 8-(N-2-fluorenylacetamido) deoxyguanosine."}
{"id": "PMID:18292", "title": "Effect of gastrin on the cell kinetics of rat gastric mucosa.", "content": "The effects of gastrin on the cell kinetics of the gastric mucosa were studied in the rats. The labelling index by tritiated thymidine of the cell in the mucous neck zone began to rise 14 hours after a single dose of tetragastrin at 100 or 1,000 microgram/kg or synthetic human gastrin at 1,000 microgram/kg and reached the peak at 18 hours. With tetragastrin 100 microgram/kg administered subcutaneously together with a depot for 35 days, observations were made on the change in the turnover rate of the gastric epithelium by means of labelling index. The turnover rate was delayed in the surface epithelium and accelerated in the cells at the lower part of the foveolae in the gastrin-administered group. The cell suspension prepared from the rat gastric mucosa by trypsin digestion was cultivated with 5 per cent of CO2 in air for 48 hours. The group which was added with 10 microgram/ml of tetragastrin showed fluctuations in the labelling index almost similar to the groups administered 100 and 1,000 microgram/kg in vivo. It might be possible to support the hypothesis that gastrin not only has a trophic effect on the mucous neck zone but it also might be concerned with the turnover of the mature stage of gastric mucosa.", "contents": "Effect of gastrin on the cell kinetics of rat gastric mucosa. The effects of gastrin on the cell kinetics of the gastric mucosa were studied in the rats. The labelling index by tritiated thymidine of the cell in the mucous neck zone began to rise 14 hours after a single dose of tetragastrin at 100 or 1,000 microgram/kg or synthetic human gastrin at 1,000 microgram/kg and reached the peak at 18 hours. With tetragastrin 100 microgram/kg administered subcutaneously together with a depot for 35 days, observations were made on the change in the turnover rate of the gastric epithelium by means of labelling index. The turnover rate was delayed in the surface epithelium and accelerated in the cells at the lower part of the foveolae in the gastrin-administered group. The cell suspension prepared from the rat gastric mucosa by trypsin digestion was cultivated with 5 per cent of CO2 in air for 48 hours. The group which was added with 10 microgram/ml of tetragastrin showed fluctuations in the labelling index almost similar to the groups administered 100 and 1,000 microgram/kg in vivo. It might be possible to support the hypothesis that gastrin not only has a trophic effect on the mucous neck zone but it also might be concerned with the turnover of the mature stage of gastric mucosa."}
{"id": "PMID:18293", "title": "[Growth and sporulation of Entomophthora virulenta Hall and Dunn in discontinuous liquid culture].", "content": "Fermented cultures of Entomophthora virulenta showed an exponential phase with a specific growth rate of 0,14 h-1. The deceleration phase was 4 times longer than the exponential phase. Sexual sporulation occurred at the end of the deceleration phase. A technique of medium replacement demonstrated that any lack of nutritive balance induced the sporulation.", "contents": "[Growth and sporulation of Entomophthora virulenta Hall and Dunn in discontinuous liquid culture]. Fermented cultures of Entomophthora virulenta showed an exponential phase with a specific growth rate of 0,14 h-1. The deceleration phase was 4 times longer than the exponential phase. Sexual sporulation occurred at the end of the deceleration phase. A technique of medium replacement demonstrated that any lack of nutritive balance induced the sporulation."}
{"id": "PMID:18294", "title": "[Interaction of thymic cells and hemopoietic stem cells. Enhancing effect on irradiated thymus repopulation].", "content": "In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with the restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells.", "contents": "[Interaction of thymic cells and hemopoietic stem cells. Enhancing effect on irradiated thymus repopulation]. In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with the restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells."}
{"id": "PMID:18295", "title": "Clinical importance of lipase determination by the turbidimetric procedure as compared with determination by a chromatrographic procedure.", "content": "The turbidimetric determination of serum lipase activity was compared with the chromatographic determination in three groups of patients, including patients affected by hepatic diseases, patients affected by pancreatic diseases and a control group. The two methods were also compared in the determination of lipase activity of human leucocytes in vitro. The results show that there is a good statistical correlation of lipase turbidimetrically determined at pH 9.15 and amylase in serum of normal individuals and in serum of patients with pancreatic diseases. There is no correlation between amylase and chromatographically determined lipase. The other types of lipase activity determined, i.e. turbidimetrically assayed at pH 5.5 and chromatographically assayed both at pH 5.5 and at pH 9.15, might be related to a different non-pancreatic enzymatic activity which is likely to lack diagnostic value. This suggests that methods of lipase determination based, for instance, on fatty acid liberation are of limited value in clinical studies on lipase.", "contents": "Clinical importance of lipase determination by the turbidimetric procedure as compared with determination by a chromatrographic procedure. The turbidimetric determination of serum lipase activity was compared with the chromatographic determination in three groups of patients, including patients affected by hepatic diseases, patients affected by pancreatic diseases and a control group. The two methods were also compared in the determination of lipase activity of human leucocytes in vitro. The results show that there is a good statistical correlation of lipase turbidimetrically determined at pH 9.15 and amylase in serum of normal individuals and in serum of patients with pancreatic diseases. There is no correlation between amylase and chromatographically determined lipase. The other types of lipase activity determined, i.e. turbidimetrically assayed at pH 5.5 and chromatographically assayed both at pH 5.5 and at pH 9.15, might be related to a different non-pancreatic enzymatic activity which is likely to lack diagnostic value. This suggests that methods of lipase determination based, for instance, on fatty acid liberation are of limited value in clinical studies on lipase."}
{"id": "PMID:18296", "title": "[Amino acid-p-nitroanilide-splitting activities in human serum (author's transl)].", "content": "Proteolytic, arylamidase-like activities of human serum are determined by using a sensitive micromethod, based upon the Bratton-Marshall-reaction, and amino acid-p-nitroanilides as substrates. Besides the alanine-aminopeptidase and the oxytocinase, the dipeptide-aminopeptidase II, a neutral peptidase, and 6 other peptidases, not yet identified by us, are differentiated with the aid of 19 substrates, by adding 8 effectors, and by incubating the enzyme tests within the pH range 6.0 to 8.4.", "contents": "[Amino acid-p-nitroanilide-splitting activities in human serum (author's transl)]. Proteolytic, arylamidase-like activities of human serum are determined by using a sensitive micromethod, based upon the Bratton-Marshall-reaction, and amino acid-p-nitroanilides as substrates. Besides the alanine-aminopeptidase and the oxytocinase, the dipeptide-aminopeptidase II, a neutral peptidase, and 6 other peptidases, not yet identified by us, are differentiated with the aid of 19 substrates, by adding 8 effectors, and by incubating the enzyme tests within the pH range 6.0 to 8.4."}
{"id": "PMID:18297", "title": "A new variant of glucosephosphate isomerase deficiency: GPI-Kortrijk.", "content": "A new case of glucosephosphate isomerase deficiency in a Belgian family is described. The activity of the enzyme was decreased to about 25-30% of the normal value. Characterization of the defect enzyme showed a decreased thermostability. Heating of the enzyme at 45 degrees C showed a loss of activity of 50% after 90 min. The pH-optimum and the KM-value for fructose 6-phosphate were normal. The electrophoretic pattern showed a faster migration. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name GPI-Kortrijk.", "contents": "A new variant of glucosephosphate isomerase deficiency: GPI-Kortrijk. A new case of glucosephosphate isomerase deficiency in a Belgian family is described. The activity of the enzyme was decreased to about 25-30% of the normal value. Characterization of the defect enzyme showed a decreased thermostability. Heating of the enzyme at 45 degrees C showed a loss of activity of 50% after 90 min. The pH-optimum and the KM-value for fructose 6-phosphate were normal. The electrophoretic pattern showed a faster migration. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name GPI-Kortrijk."}
{"id": "PMID:18298", "title": "Purification and properties of urinary alkaline ribonucleases from patients with nephrotic syndrome.", "content": "Four urinary alkaline ribonucleases (RNase, EC 3.1.4.22) were purified from patients with nephrotic syndrome using phosphocellulose, DEAE-cellulose and Sephadex G-75 chromatographiy. These enzymes were designated as RNases 1--4, respectively, in order of elution on phosphocellulose chromatography. The respective purification of each fraction was 41-, 23-, 34- and 27-fold with a total recovery of 25%. The pH optima of these RNases were around 8.5 with Tris/HCl buffer and the reaction was activated by mono- and divalent cations, such as Na+, K+, Mg2+ and Ca2+, but inhibited by Fe2+, Cu2+ and Zn2+. EDTA had little effect on the velocity of reaction. The molecular weights of RNases 1--4 were estimated by gel filtration as 45 000, 32 000, 20 000, and 13 000, respectively. Each enzyme hydrolyzed pyrimidine nucleotides preferentially with higher affinity for poly(C) than poly (U) as determined with synthetic polymers and was free from other nucleolytic enzymes. The patients with renal disorders excreted one to four RNases in urine and the number of enzymes increased as the concentration of urinary protein increased. On the other hand, normal subjects excreted a single fraction essentially identical to RNase 1.", "contents": "Purification and properties of urinary alkaline ribonucleases from patients with nephrotic syndrome. Four urinary alkaline ribonucleases (RNase, EC 3.1.4.22) were purified from patients with nephrotic syndrome using phosphocellulose, DEAE-cellulose and Sephadex G-75 chromatographiy. These enzymes were designated as RNases 1--4, respectively, in order of elution on phosphocellulose chromatography. The respective purification of each fraction was 41-, 23-, 34- and 27-fold with a total recovery of 25%. The pH optima of these RNases were around 8.5 with Tris/HCl buffer and the reaction was activated by mono- and divalent cations, such as Na+, K+, Mg2+ and Ca2+, but inhibited by Fe2+, Cu2+ and Zn2+. EDTA had little effect on the velocity of reaction. The molecular weights of RNases 1--4 were estimated by gel filtration as 45 000, 32 000, 20 000, and 13 000, respectively. Each enzyme hydrolyzed pyrimidine nucleotides preferentially with higher affinity for poly(C) than poly (U) as determined with synthetic polymers and was free from other nucleolytic enzymes. The patients with renal disorders excreted one to four RNases in urine and the number of enzymes increased as the concentration of urinary protein increased. On the other hand, normal subjects excreted a single fraction essentially identical to RNase 1."}
{"id": "PMID:18299", "title": "Properties of the thyroxine (T4) monodeiodinating system in rat liver homogenate.", "content": "The monodeiodination of T4 in rat liver homogenate was studied. The two possible products of this reaction show very different properties. The metabolically very active T3 is rather stable in this system whereas the biological inactive reverse T3 (rT3) disappears very rapidly. This explains the low apparent rT3 production in the incubation mixture even under optimal conditions and the peculiar pH profile. The T4 to T3 converting reaction can be increased by the addition of mercaptoethanol to the medium; no further activation is possible by several cofactors tested. The apparent KM of the reaction is 1.6 x 10(-6) M. Reverse T3 does inhibit the reaction non competitive; Ki = 2 x 10 (10-8) M. Alpha-methyl-para-tyrosine, a specific inhibitor of tyrosine hydroxylase, has no significant effect on the reaction.", "contents": "Properties of the thyroxine (T4) monodeiodinating system in rat liver homogenate. The monodeiodination of T4 in rat liver homogenate was studied. The two possible products of this reaction show very different properties. The metabolically very active T3 is rather stable in this system whereas the biological inactive reverse T3 (rT3) disappears very rapidly. This explains the low apparent rT3 production in the incubation mixture even under optimal conditions and the peculiar pH profile. The T4 to T3 converting reaction can be increased by the addition of mercaptoethanol to the medium; no further activation is possible by several cofactors tested. The apparent KM of the reaction is 1.6 x 10(-6) M. Reverse T3 does inhibit the reaction non competitive; Ki = 2 x 10 (10-8) M. Alpha-methyl-para-tyrosine, a specific inhibitor of tyrosine hydroxylase, has no significant effect on the reaction."}
{"id": "PMID:18300", "title": "Conversion of T4 to T3 and rT3 and their cytoplasmic binding: pH dependency.", "content": "The fate of T4 in target organs is conversion to T3 which is mainly responsible for the nuclear action of thyroid hormones. To further investigate this converting step the increase of T3 and its analogue rT3 in rat liver microsomes was measured by specific radioimmunoassays after adding T4 to the incubation medium. Maximal increase of T3 occurred at pH 6.0 and of rT3 at pH 9.5 indicating that two different enzymic systems may be involved in the deiodination of the tyrosyl or the phenolic ring of T4. An increase in the binding capacity of cytosol proteins for T4, T3 and rT3 with rising pH demonstrates that there is also a pH dependency of the cytoplasmic binding of these iodothyronines. These reaction conditions should not only be considered in in vitro experiments, but may also be of importance in modifying the availability of T3 for its nuclear receptors.", "contents": "Conversion of T4 to T3 and rT3 and their cytoplasmic binding: pH dependency. The fate of T4 in target organs is conversion to T3 which is mainly responsible for the nuclear action of thyroid hormones. To further investigate this converting step the increase of T3 and its analogue rT3 in rat liver microsomes was measured by specific radioimmunoassays after adding T4 to the incubation medium. Maximal increase of T3 occurred at pH 6.0 and of rT3 at pH 9.5 indicating that two different enzymic systems may be involved in the deiodination of the tyrosyl or the phenolic ring of T4. An increase in the binding capacity of cytosol proteins for T4, T3 and rT3 with rising pH demonstrates that there is also a pH dependency of the cytoplasmic binding of these iodothyronines. These reaction conditions should not only be considered in in vitro experiments, but may also be of importance in modifying the availability of T3 for its nuclear receptors."}
{"id": "PMID:18301", "title": "PZ-peptidase activity in human uterine cervix in pregnancy at term.", "content": "PZ-peptidase (EC 3.4.--) was detected in human uterine cervix distributed in the soluble fraction after 100 000 x g centrifugation. Optimum pH for PZ-peptidase was observed to be pH 7.2--7.4, except for two of the preparations examined. PZ-peptidase activity was found to significantly increase in pregnancy at term as compared with that in a control group.", "contents": "PZ-peptidase activity in human uterine cervix in pregnancy at term. PZ-peptidase (EC 3.4.--) was detected in human uterine cervix distributed in the soluble fraction after 100 000 x g centrifugation. Optimum pH for PZ-peptidase was observed to be pH 7.2--7.4, except for two of the preparations examined. PZ-peptidase activity was found to significantly increase in pregnancy at term as compared with that in a control group."}
{"id": "PMID:18303", "title": "Diagnosis of Pompe's disease in cultured skin fibroblasts and primary amniotic fluid cells using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate.", "content": "The possible interference of neutral alpha-D-glucosidase in the diagnosis of Pompe's disease using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate for the assay of acid alpha-D-glucosidase was investigated. The pH profile of alpha-D-glucosidase in control skin fibroblasts and amniotic fluid cells showed two peaks of activity. The shape of the pH profile depended upon whether or not the extract was added to the buffer before the substrate. If extract was added to the buffer before the substrate, a greater separation was obtained between the two peaks of activity. The neutral alpha-D-glucosidase activity could be totally removed by preliminary precipitation at pH 5.0. Following acid region whilst Pompe's cells had no activity enabling a clear distinction to be made between carriers and the disease state.", "contents": "Diagnosis of Pompe's disease in cultured skin fibroblasts and primary amniotic fluid cells using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate. The possible interference of neutral alpha-D-glucosidase in the diagnosis of Pompe's disease using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate for the assay of acid alpha-D-glucosidase was investigated. The pH profile of alpha-D-glucosidase in control skin fibroblasts and amniotic fluid cells showed two peaks of activity. The shape of the pH profile depended upon whether or not the extract was added to the buffer before the substrate. If extract was added to the buffer before the substrate, a greater separation was obtained between the two peaks of activity. The neutral alpha-D-glucosidase activity could be totally removed by preliminary precipitation at pH 5.0. Following acid region whilst Pompe's cells had no activity enabling a clear distinction to be made between carriers and the disease state."}
{"id": "PMID:18304", "title": "A new method for peptidase activity measurement in serum and tissues, using L-Leu-L-Leu as substrate.", "content": "Peptidase-free L-amino-acid oxidase was purified from venom of Agkistrodon caliginosus and was used for the determination of serum peptidase (EC 3.4.1.-) activity with L-Leu-L-Leu as substrate. The peptidase activity in human serum rose remarkably in liver diseases, and had a significant correlation with serum transaminase activity. The peptidase activity in serum of rats treated with CCl4 was higher than that of normal rats. After Cellogel electrophoresis the zymogram of peptidase from human liver using di- or tripeptide as substrate appeared with three active bands; however, peptidase in serum of a patient with acute hepatitis showed only one active band.", "contents": "A new method for peptidase activity measurement in serum and tissues, using L-Leu-L-Leu as substrate. Peptidase-free L-amino-acid oxidase was purified from venom of Agkistrodon caliginosus and was used for the determination of serum peptidase (EC 3.4.1.-) activity with L-Leu-L-Leu as substrate. The peptidase activity in human serum rose remarkably in liver diseases, and had a significant correlation with serum transaminase activity. The peptidase activity in serum of rats treated with CCl4 was higher than that of normal rats. After Cellogel electrophoresis the zymogram of peptidase from human liver using di- or tripeptide as substrate appeared with three active bands; however, peptidase in serum of a patient with acute hepatitis showed only one active band."}
{"id": "PMID:18305", "title": "Determination of the Tamm and Horsfall glycoprotein in human urine.", "content": "A method for the routine determination of the Tamm and Horsfall glycoprotein in human urine is presented. The method is based on quantitative electroimmunoassay. It was demonstrated that the solubility of the Tamm and Horsfall glycoprotein was dependent on urinary ionic strength and pH. To minimize these variables all urines were buffered to pH 5.5 and then preincubated at 37 degrees C in 0.3% sodium dodecyl sulphate. This procedure solubilized and maintained the Tamm and Horsfall glycoprotein in solution. Excess sodium dodecyl sulphate was removed by gel filtration before the quantities of the Tamm and Horsfall glycoprotein were determined by electroimmunoassay. The method is simple, reproducible, has high precision and compares favourably with earlier published methods for the determinations of the Tamm and Horsfall glycoprotein.", "contents": "Determination of the Tamm and Horsfall glycoprotein in human urine. A method for the routine determination of the Tamm and Horsfall glycoprotein in human urine is presented. The method is based on quantitative electroimmunoassay. It was demonstrated that the solubility of the Tamm and Horsfall glycoprotein was dependent on urinary ionic strength and pH. To minimize these variables all urines were buffered to pH 5.5 and then preincubated at 37 degrees C in 0.3% sodium dodecyl sulphate. This procedure solubilized and maintained the Tamm and Horsfall glycoprotein in solution. Excess sodium dodecyl sulphate was removed by gel filtration before the quantities of the Tamm and Horsfall glycoprotein were determined by electroimmunoassay. The method is simple, reproducible, has high precision and compares favourably with earlier published methods for the determinations of the Tamm and Horsfall glycoprotein."}
{"id": "PMID:18306", "title": "Heterogeneity of erythrocyte pyruvate kinase deficiency and related metabolic disorders in patients with hematological diseases.", "content": "In several patients suffering from congenital non-spherocytic hemolytic anemia or from malignant hemotological disorder associated with erythrocyte pyruvate kinase (PK) deficiency, a metabolic study has been carried out involving the following biochemical determinations: assay of red cell enzyme activities; estimation of glucose consumption; measurement of the rate of glycolytic intermediates; and, in some cases, enzyme purification and characterization of the PK variant. Metabolic equilibrium most probably does not depend on kinetic characteristics of PK molecules. Furthermore, the data obtained allow separation of cases with congenital non-spherocytic hemolytic anemia (hereditary defect) and acquired PK deficiencies.", "contents": "Heterogeneity of erythrocyte pyruvate kinase deficiency and related metabolic disorders in patients with hematological diseases. In several patients suffering from congenital non-spherocytic hemolytic anemia or from malignant hemotological disorder associated with erythrocyte pyruvate kinase (PK) deficiency, a metabolic study has been carried out involving the following biochemical determinations: assay of red cell enzyme activities; estimation of glucose consumption; measurement of the rate of glycolytic intermediates; and, in some cases, enzyme purification and characterization of the PK variant. Metabolic equilibrium most probably does not depend on kinetic characteristics of PK molecules. Furthermore, the data obtained allow separation of cases with congenital non-spherocytic hemolytic anemia (hereditary defect) and acquired PK deficiencies."}
{"id": "PMID:18312", "title": "Clonidine and the vasodilating beta blocker antihypertensive drug interaction.", "content": "Because propranolol is contraindicated in some patients and since clonidine can decrease heart rate and renin release, clonidine was substituted for propranolol in 14 severely hypertensive minoxidil-treated outpatients. Clonidine induced weight loss which, since plasma concentrations were not suppressed, was not due to inhibition of release of antidiuretic hormone or renin. These endocrine interrelations were confirmed by later administration of clonidine to 4 of the subjects under controlled circumstances in our General Clinical Research Center. When substituted for propranolol, clonidine controlled blood pressure and heart rate in 8 of the 9 outpatients whose blood pressure had been previously well controlled. Clonidine and propranolol had additive antihypertensive effects in the other 5 patients. Thus, clonidine can substitute for propranolol or when added to the propranolol-vasodilator combination supply an additional blood pressure-lowering effects. This substitution or addition results in an increase in side effects. In addition, clonidine has a diuretic action under these circumstances by an unknown mechanism.", "contents": "Clonidine and the vasodilating beta blocker antihypertensive drug interaction. Because propranolol is contraindicated in some patients and since clonidine can decrease heart rate and renin release, clonidine was substituted for propranolol in 14 severely hypertensive minoxidil-treated outpatients. Clonidine induced weight loss which, since plasma concentrations were not suppressed, was not due to inhibition of release of antidiuretic hormone or renin. These endocrine interrelations were confirmed by later administration of clonidine to 4 of the subjects under controlled circumstances in our General Clinical Research Center. When substituted for propranolol, clonidine controlled blood pressure and heart rate in 8 of the 9 outpatients whose blood pressure had been previously well controlled. Clonidine and propranolol had additive antihypertensive effects in the other 5 patients. Thus, clonidine can substitute for propranolol or when added to the propranolol-vasodilator combination supply an additional blood pressure-lowering effects. This substitution or addition results in an increase in side effects. In addition, clonidine has a diuretic action under these circumstances by an unknown mechanism."}
{"id": "PMID:18310", "title": "Plasmalemmal calcium in cardiac excitation-contraction coupling.", "content": "1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force. 2. In mammalian heart there is a network of large transverse tubules throughout the cell. These structures are regularly arranged at the level of the sarcomeric Z- and I-lines and increase the cell surface by a factor of ten. 3. Experimental evidence favours the assumption that the plasmalemma could be the site of a loosely bound superficial Ca fraction which becomes ionized upon depolarization and is again bound upon repolarization of the cardiac cell membrane. 4. A mechanism is discussed which bases the excitation-contraction coupling process on a physicochemical interaction of calcium with membrane phospholipids. The degree of interaction is thought to be governed by the transmembrane electric field, the induced dipole moment of membrane constituents, and proton activity within the membrane.", "contents": "Plasmalemmal calcium in cardiac excitation-contraction coupling. 1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force. 2. In mammalian heart there is a network of large transverse tubules throughout the cell. These structures are regularly arranged at the level of the sarcomeric Z- and I-lines and increase the cell surface by a factor of ten. 3. Experimental evidence favours the assumption that the plasmalemma could be the site of a loosely bound superficial Ca fraction which becomes ionized upon depolarization and is again bound upon repolarization of the cardiac cell membrane. 4. A mechanism is discussed which bases the excitation-contraction coupling process on a physicochemical interaction of calcium with membrane phospholipids. The degree of interaction is thought to be governed by the transmembrane electric field, the induced dipole moment of membrane constituents, and proton activity within the membrane."}
{"id": "PMID:18313", "title": "Metabolism of flurazepam by the small intestine.", "content": "The metabolism of flurazepam-5-14C has been studied in man following catheterization of the portal and hepatic veins. Flurazepam was administered through a tube into the stomach in one patient and into the duodenum in two patients. Thin-layer chromatographs of portal vein blood showed that there was a rapid and early appearance of metabolites of flurazepam consistent with the metabolism of the flurazepam by the intestinal mucosa and at times when the concentrations in the hepatic vein and peripheral blood were very much lower than those in the portal vein. The major metabolites identified in portal vein blood were the mono- and didesetyl metabolies of flurazepam. Considerable hepatic uptake of flurazepam and its metabolites occurred, as evidenced by the lower concentrations of the parent compound and metabolites in the hepatic vein. Thus, \"first-pass\" metabolism of flurazepam following oral administration occurs in the small bowel mucosa of man as well as in the liver.", "contents": "Metabolism of flurazepam by the small intestine. The metabolism of flurazepam-5-14C has been studied in man following catheterization of the portal and hepatic veins. Flurazepam was administered through a tube into the stomach in one patient and into the duodenum in two patients. Thin-layer chromatographs of portal vein blood showed that there was a rapid and early appearance of metabolites of flurazepam consistent with the metabolism of the flurazepam by the intestinal mucosa and at times when the concentrations in the hepatic vein and peripheral blood were very much lower than those in the portal vein. The major metabolites identified in portal vein blood were the mono- and didesetyl metabolies of flurazepam. Considerable hepatic uptake of flurazepam and its metabolites occurred, as evidenced by the lower concentrations of the parent compound and metabolites in the hepatic vein. Thus, \"first-pass\" metabolism of flurazepam following oral administration occurs in the small bowel mucosa of man as well as in the liver."}
{"id": "PMID:18311", "title": "A study in mice of bromo and chloro acylurea analogues of the sedative-hypnotic bromureides.", "content": "1. A series of 1-(2-chloroacyl)ureas, related to the sedative-hypnotic drugs bromvaletone and carbromal, was synthesized and tested in mice to determine central depressant and acute toxic effects. Four 1-(2-bromoacyl)ureas and two 3-halo compounds were included for comparison. 2. Large variations in potency were seen between the compounds. Much of this can be ascribed to differences in lipophilicity. Among homologous 1-(2-chloroacyl)ureas, those with 6 acyl carbons had maximal potency. Among groups of structural isomers, the most potent were 2-halo, 3-alkyl substituted compounds. 3. The most potent compounds were also those with the largest ratios of hypnotic to lethal activity. 4. The variation in the onset and duration of action of these compounds enables a choice to be made for a compound with a particular set of characteristics.", "contents": "A study in mice of bromo and chloro acylurea analogues of the sedative-hypnotic bromureides. 1. A series of 1-(2-chloroacyl)ureas, related to the sedative-hypnotic drugs bromvaletone and carbromal, was synthesized and tested in mice to determine central depressant and acute toxic effects. Four 1-(2-bromoacyl)ureas and two 3-halo compounds were included for comparison. 2. Large variations in potency were seen between the compounds. Much of this can be ascribed to differences in lipophilicity. Among homologous 1-(2-chloroacyl)ureas, those with 6 acyl carbons had maximal potency. Among groups of structural isomers, the most potent were 2-halo, 3-alkyl substituted compounds. 3. The most potent compounds were also those with the largest ratios of hypnotic to lethal activity. 4. The variation in the onset and duration of action of these compounds enables a choice to be made for a compound with a particular set of characteristics."}
{"id": "PMID:18316", "title": "The effect of chronic frusemide administration on intracellular potassium, sodium and pH of cardiac and skeletal muscle.", "content": "1. Chronic administration of frusemide in large doses of 4 mg day-1 kg-1 for 3 weeks caused a significant reduction of cell water in rabbit cardiac and skeletal muscle. Intracellular Na+ concentration, intracellular pH and extracellular space was unchanged in both tissues. Intracellular K+ concentration increased slightly in both cardiac and skeletal muscle. 2. It is concluded that frusemide does not reduce intracellular K+ concentration in cardiac or skeletal muscle of normal animals receiving a normal oral potassium intake.", "contents": "The effect of chronic frusemide administration on intracellular potassium, sodium and pH of cardiac and skeletal muscle. 1. Chronic administration of frusemide in large doses of 4 mg day-1 kg-1 for 3 weeks caused a significant reduction of cell water in rabbit cardiac and skeletal muscle. Intracellular Na+ concentration, intracellular pH and extracellular space was unchanged in both tissues. Intracellular K+ concentration increased slightly in both cardiac and skeletal muscle. 2. It is concluded that frusemide does not reduce intracellular K+ concentration in cardiac or skeletal muscle of normal animals receiving a normal oral potassium intake."}
{"id": "PMID:18319", "title": "Essential facets of radiological diagnosis of extremity trauma.", "content": "Trauma to the extremities is sometimes dismissed as relatively unimportant in certain radiologic circles. In many instances, radiologic responsibility is denied and relegated to the orthopedist. Although the radiologic manifestations of much trauma to the extremities is clear cut and does not require sophisticated techniques or interpretation, there are many diagnoses which require innovative techniques and a knowledge of mechanisms of injury as well as the subtle oseous and soft tissue manifestations which may be confronted radiologically. The above factors will be stressed along with the need for the fundamental knowledge of radiologic anatomy which is required in order to appreciate some of the more subtle changes of extremity trauma.", "contents": "Essential facets of radiological diagnosis of extremity trauma. Trauma to the extremities is sometimes dismissed as relatively unimportant in certain radiologic circles. In many instances, radiologic responsibility is denied and relegated to the orthopedist. Although the radiologic manifestations of much trauma to the extremities is clear cut and does not require sophisticated techniques or interpretation, there are many diagnoses which require innovative techniques and a knowledge of mechanisms of injury as well as the subtle oseous and soft tissue manifestations which may be confronted radiologically. The above factors will be stressed along with the need for the fundamental knowledge of radiologic anatomy which is required in order to appreciate some of the more subtle changes of extremity trauma."}
{"id": "PMID:18320", "title": "Some factors affecting testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol secretion by invitro perfused rabbit testes.", "content": "Intra-arterial infusion of testosterone-3H gave rise to tritiated dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3beta,17 beta-diol in spermatic venous effluent of the perfused rabbit testis-epididymis. Mass spectrometric measurements confirmed that these four androgens were present in spermatic venous effluent of the perfused rabbit testis-epididymis. Gas liquid chromatographic measurement showed that testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol were secreted in similar amounts by the in vitro perfused and in situ rabbit testis-epididymis results obtained by perfusing the testis minus the epididymis suggested that the bulk of these androgens originate from the catabolism of testosterone within the testis rather than the epididymis. Suprisingly, germinal epithelium destruction by heat failed to alter the testosterone, dihydrotestosterone and 5 alpha-androstan-3 alpha,17 beta-diol secretion by the in vitro perfused rabbit testis. In contrast, the secretion of 5 alpha-androstan-3 beta,17 beta-diol was significantly (P less than 0.05) reduced in the same cryptorchid compared to control testes.", "contents": "Some factors affecting testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol secretion by invitro perfused rabbit testes. Intra-arterial infusion of testosterone-3H gave rise to tritiated dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3beta,17 beta-diol in spermatic venous effluent of the perfused rabbit testis-epididymis. Mass spectrometric measurements confirmed that these four androgens were present in spermatic venous effluent of the perfused rabbit testis-epididymis. Gas liquid chromatographic measurement showed that testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol were secreted in similar amounts by the in vitro perfused and in situ rabbit testis-epididymis results obtained by perfusing the testis minus the epididymis suggested that the bulk of these androgens originate from the catabolism of testosterone within the testis rather than the epididymis. Suprisingly, germinal epithelium destruction by heat failed to alter the testosterone, dihydrotestosterone and 5 alpha-androstan-3 alpha,17 beta-diol secretion by the in vitro perfused rabbit testis. In contrast, the secretion of 5 alpha-androstan-3 beta,17 beta-diol was significantly (P less than 0.05) reduced in the same cryptorchid compared to control testes."}
{"id": "PMID:18322", "title": "Testicular androgen binding protein (ABP) - a parameter of Sertoli cell secretory function.", "content": "Using ABP as an index of Sertoli cell secretory function, several important features of the Sertoli cell have emerged: 1. The stimulation of ABP production by FSH clearly points to the Sertoli cell as a target cell for FSH (3,4,9-16,21,24). 2. The dramatic effects of androgens on ABP production both in immature and mature rats also suggest that the Sertoli cell is a target cell for androgen (3,12,14,16,25). 3. The striking reduction in ABP production in the cryptorchid testis raises the question whether impairment of Sertoli cell function is the primary reason for the loss of germ cells that occurs in this condition (20). 4. Drugs like nitrofurazone or ethionine, or X-irradiation only slightly affect the secretory function of the Sertoli cells (ABP production), indicating that these treatments most probably have direct effects on the germ cells as well. Thus, measurement of ABP production rate is a very important tool in order to evaluate how hormones, drugs and physical injuries might affect the secretory function of the Sertoli cell. This test system might be of great use in order to study the physiology and hormonal regulation of the Sertoli cells. It might also be valuable in pharmacological and toxicological studies.", "contents": "Testicular androgen binding protein (ABP) - a parameter of Sertoli cell secretory function. Using ABP as an index of Sertoli cell secretory function, several important features of the Sertoli cell have emerged: 1. The stimulation of ABP production by FSH clearly points to the Sertoli cell as a target cell for FSH (3,4,9-16,21,24). 2. The dramatic effects of androgens on ABP production both in immature and mature rats also suggest that the Sertoli cell is a target cell for androgen (3,12,14,16,25). 3. The striking reduction in ABP production in the cryptorchid testis raises the question whether impairment of Sertoli cell function is the primary reason for the loss of germ cells that occurs in this condition (20). 4. Drugs like nitrofurazone or ethionine, or X-irradiation only slightly affect the secretory function of the Sertoli cells (ABP production), indicating that these treatments most probably have direct effects on the germ cells as well. Thus, measurement of ABP production rate is a very important tool in order to evaluate how hormones, drugs and physical injuries might affect the secretory function of the Sertoli cell. This test system might be of great use in order to study the physiology and hormonal regulation of the Sertoli cells. It might also be valuable in pharmacological and toxicological studies."}
{"id": "PMID:18324", "title": "Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. I. Results obtained after hybridization of human cells carrying reciprocal translocations involving chromosome 1.", "content": "Regional localization studies of genes coding for human PGD, PPH1, PGM1, UGPP, GuK1, Pep-C, and FH, which have been assigned to chromosome 1, were performed with man-Chinese hamster somatic cell hybrids, Informative hybrids that retained fragments of the human chromosome 1 were produced by fusion of hamster cells with human cells carrying reciprocal translocations involving chromosome 1. Analysis of the hybrids that retained one of the translocation chromosomes or de novo rearrangements involving the human 1 revealed the following gene positions: PGD and PPH1 in 1pter leads to 1p32, PGM1 in 1p32 leads to 1p22, UGPP and GuK1 in 1q21 leads to 1q42, FH in 1qter leads to 1q42, and Pep-C probably in 1q42.", "contents": "Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. I. Results obtained after hybridization of human cells carrying reciprocal translocations involving chromosome 1. Regional localization studies of genes coding for human PGD, PPH1, PGM1, UGPP, GuK1, Pep-C, and FH, which have been assigned to chromosome 1, were performed with man-Chinese hamster somatic cell hybrids, Informative hybrids that retained fragments of the human chromosome 1 were produced by fusion of hamster cells with human cells carrying reciprocal translocations involving chromosome 1. Analysis of the hybrids that retained one of the translocation chromosomes or de novo rearrangements involving the human 1 revealed the following gene positions: PGD and PPH1 in 1pter leads to 1p32, PGM1 in 1p32 leads to 1p22, UGPP and GuK1 in 1q21 leads to 1q42, FH in 1qter leads to 1q42, and Pep-C probably in 1q42."}
{"id": "PMID:18325", "title": "Brain monoamines act through the prostaglandin release to influence the body temperature.", "content": "In the present study, the thermal responses induced by intraventicular administration of pyrogen prostaglandin E1, the brain monoamines norepinephrine and serotonin, and the antipyretic sodium acetylsalicylate (aspirin) were measured in conscious rabbits to assess the possible involvement of these substances in fever production. The body temperatures, metabolic rate, respiratory evaporative heat loss and vasomotor activity in response to the administration of these drugs were measured. The results showed that sodium acetylsalicylate, an inhibitor of prostaglandin synthetase, antagonizes the norepinephrine induced fever but not the prostaglandin fever. The data also showed that the serotonin induced hypothermia was reversed by prostaglandin administration. Thus, the fact strongly suggest that the prostaglandin E1 serves as a fever-prducing mediator in the central nervous system. Also, the norepinephrine fever and serotonin hpyothermia, respectively, may be associated with an increase and a decrease in prostaglandin synthesis in the brain.", "contents": "Brain monoamines act through the prostaglandin release to influence the body temperature. In the present study, the thermal responses induced by intraventicular administration of pyrogen prostaglandin E1, the brain monoamines norepinephrine and serotonin, and the antipyretic sodium acetylsalicylate (aspirin) were measured in conscious rabbits to assess the possible involvement of these substances in fever production. The body temperatures, metabolic rate, respiratory evaporative heat loss and vasomotor activity in response to the administration of these drugs were measured. The results showed that sodium acetylsalicylate, an inhibitor of prostaglandin synthetase, antagonizes the norepinephrine induced fever but not the prostaglandin fever. The data also showed that the serotonin induced hypothermia was reversed by prostaglandin administration. Thus, the fact strongly suggest that the prostaglandin E1 serves as a fever-prducing mediator in the central nervous system. Also, the norepinephrine fever and serotonin hpyothermia, respectively, may be associated with an increase and a decrease in prostaglandin synthesis in the brain."}
{"id": "PMID:18328", "title": "[Recurrent periarteritis nodosa with predominantly cerebral signs in children (author's transl)].", "content": "Periarteritis nodosa occurs also in children and has the same wide spectrum of signs and symptoms as in adults. In a 4 1/2 year-old girl the disease at first was characterised by cerebral, encephalitis-like symptoms, arterial hypertension, intestinal wall necrosis and, finally, pericardial tamponade as a result of rupture of an arteritic coronary artery aneurysm. An earlier attack had involved liver and skeletal muscle, with necrosis in the liver. Peculiar morphological features within the \"classical\" course of periarteritis nodosa are endarteritic changes of single retroperitoneal and coronary arteries.", "contents": "[Recurrent periarteritis nodosa with predominantly cerebral signs in children (author's transl)]. Periarteritis nodosa occurs also in children and has the same wide spectrum of signs and symptoms as in adults. In a 4 1/2 year-old girl the disease at first was characterised by cerebral, encephalitis-like symptoms, arterial hypertension, intestinal wall necrosis and, finally, pericardial tamponade as a result of rupture of an arteritic coronary artery aneurysm. An earlier attack had involved liver and skeletal muscle, with necrosis in the liver. Peculiar morphological features within the \"classical\" course of periarteritis nodosa are endarteritic changes of single retroperitoneal and coronary arteries."}
{"id": "PMID:18329", "title": "Drug-induced cardiovascular diseases.", "content": "A wide variety of drugs may be associated with serious cardiovascular toxicity. Toxicity due to drugs primarily used for treating cardiovascular toxicity. Toxicity due to drugs primarily used for treating cardiac disorders is the most extensively documented, especially the arrhythmias due to digitalis glycosides. Various arrhythmias are also caused by toxic levels of many antiarrhythmic agents including quinidine, procainamide and phenytotin. Myocardial depression and heart failure are serious side-effects of beta-adrenoceptor blocking agents and myocardial ischaemia due to sympathominetic amines may result from both direct and indirect mechanisms. The many toxic reactions in the cardiovascular system due to non-cardiac drugs are less widely known and for the most part less clearly understood. Many remain controversial at the current time; for example, the diathesis toward thromboembolism in women taking oral contraceptives. Potential cardiac toxicity due to drugs used in the rapidly expanding sphere of anti-neoplastic chemotherapy is exemplified by the cardiomyopathy-like toxicities of doxorubicin and daunorubicin. Many of the psychotherapeutic drugs including phenothiazine antipsychotics and tricyclic antidepressants have arrhythmogenic potential.", "contents": "Drug-induced cardiovascular diseases. A wide variety of drugs may be associated with serious cardiovascular toxicity. Toxicity due to drugs primarily used for treating cardiovascular toxicity. Toxicity due to drugs primarily used for treating cardiac disorders is the most extensively documented, especially the arrhythmias due to digitalis glycosides. Various arrhythmias are also caused by toxic levels of many antiarrhythmic agents including quinidine, procainamide and phenytotin. Myocardial depression and heart failure are serious side-effects of beta-adrenoceptor blocking agents and myocardial ischaemia due to sympathominetic amines may result from both direct and indirect mechanisms. The many toxic reactions in the cardiovascular system due to non-cardiac drugs are less widely known and for the most part less clearly understood. Many remain controversial at the current time; for example, the diathesis toward thromboembolism in women taking oral contraceptives. Potential cardiac toxicity due to drugs used in the rapidly expanding sphere of anti-neoplastic chemotherapy is exemplified by the cardiomyopathy-like toxicities of doxorubicin and daunorubicin. Many of the psychotherapeutic drugs including phenothiazine antipsychotics and tricyclic antidepressants have arrhythmogenic potential."}
{"id": "PMID:18331", "title": "[Telemetry of the tissue Ph value under the effect of local anesthetics. Preliminary report].", "content": "After discussing the problems involved in in vivo pH measurements, pH telemetry is presented as a new method. Long-term in vivo measurements of the pH are intended to be performed by means of a miniature transmitter implanted into the subcutaneous tissue of guinea pigs.", "contents": "[Telemetry of the tissue Ph value under the effect of local anesthetics. Preliminary report]. After discussing the problems involved in in vivo pH measurements, pH telemetry is presented as a new method. Long-term in vivo measurements of the pH are intended to be performed by means of a miniature transmitter implanted into the subcutaneous tissue of guinea pigs."}
{"id": "PMID:18332", "title": "[The salivary fluoride level after administration of fluorides and fluoride complex salts].", "content": "Compounds of fluorine and Si or Fe are found in nature and are sometimes formed from F ions in the stomach. The chemistry of the release of resorbable F ions from such compounds in the intestinal tract is described. To demonstrate fluorine availability at the enamel surface daily profiles of fluorine concentration in the saliva of seven subjects after a single administration of a NaF and Na3FeF6 tablet are presented and their effect on the remineralization of the dental enamel described.", "contents": "[The salivary fluoride level after administration of fluorides and fluoride complex salts]. Compounds of fluorine and Si or Fe are found in nature and are sometimes formed from F ions in the stomach. The chemistry of the release of resorbable F ions from such compounds in the intestinal tract is described. To demonstrate fluorine availability at the enamel surface daily profiles of fluorine concentration in the saliva of seven subjects after a single administration of a NaF and Na3FeF6 tablet are presented and their effect on the remineralization of the dental enamel described."}
{"id": "PMID:18334", "title": "[Change in the mental contents in the paradoxical stage and in stage 2 under the effects of a benzodiazepine, flunitrazepam].", "content": "In some insomniacs under flunitrazepam treatment is noted on one hand a global increase of dream memories, and on the other hand an increase of dreams with unpleasant or anxious contents. The present investigation is intended first to test the hypothesis of a possible increase of mental contents in sleep outside the paradoxical phases, to account for the increase of dream memories without concomitant increase of paradoxical stage. Second it intends to investigate if the increase of unpleasant dreams may be found in the normal subject in laboratory.", "contents": "[Change in the mental contents in the paradoxical stage and in stage 2 under the effects of a benzodiazepine, flunitrazepam]. In some insomniacs under flunitrazepam treatment is noted on one hand a global increase of dream memories, and on the other hand an increase of dreams with unpleasant or anxious contents. The present investigation is intended first to test the hypothesis of a possible increase of mental contents in sleep outside the paradoxical phases, to account for the increase of dream memories without concomitant increase of paradoxical stage. Second it intends to investigate if the increase of unpleasant dreams may be found in the normal subject in laboratory."}
{"id": "PMID:18338", "title": "Influence of temperature on the determination of enzyme activities in human serum. gamma-Glutamyl transferase.", "content": "Optimum reaction conditions for determination of gamma-glutamyl transferase were studied at 25, 30 and 37 degrees C using a kinetic test and gamma-glutamyl-3-carboxy-4-nitranilide as substrate. There was no dependence on temperature of half saturation constants of gamma-glutamyl-3-carboxy-4-nitranilide. The corresponding constants for glycylglycine were influenced by temperature and the pH. The optimum showed a dependence upon temperature. In Arrhenius' plot, a deviation from straight line can be observed only above 35 degrees C. The influence of temperature on the determination of enzyme activities in human serum are discussed.", "contents": "Influence of temperature on the determination of enzyme activities in human serum. gamma-Glutamyl transferase. Optimum reaction conditions for determination of gamma-glutamyl transferase were studied at 25, 30 and 37 degrees C using a kinetic test and gamma-glutamyl-3-carboxy-4-nitranilide as substrate. There was no dependence on temperature of half saturation constants of gamma-glutamyl-3-carboxy-4-nitranilide. The corresponding constants for glycylglycine were influenced by temperature and the pH. The optimum showed a dependence upon temperature. In Arrhenius' plot, a deviation from straight line can be observed only above 35 degrees C. The influence of temperature on the determination of enzyme activities in human serum are discussed."}
{"id": "PMID:18339", "title": "Guanosine triphosphate: 5-hydroxylysine phosphotransferase in rat kidney cortex.", "content": "An enzyme which catalyzes the transfer of the gamma-phosphate from GTP onto 5-hydroxylysine was partially purified from rat kidney cortex by means of acid precipitation and DEAE-Sephadex A-50 column chromatography. The enzyme activity was assayed by measuring the transfer of [32P] from gamma-[32P]-GTP to materials not adsorbed by charcoal. This partially purified enzyme showed essentially no GTP phosphohydrolase activity and an optimal pH of 8.0. An apparent Km of about 23.8 mumol/1 was obtained with respect to 5-hydroxylysine. Mg2+ was required for the activity of this enzyme. Ethanolamine, L-lysine, L-ornithine and choline inhibited the enzyme but L-threonine, L-serine and hydroxy-L-proline did not. None of these compounds severed as substrate for this enzyme.", "contents": "Guanosine triphosphate: 5-hydroxylysine phosphotransferase in rat kidney cortex. An enzyme which catalyzes the transfer of the gamma-phosphate from GTP onto 5-hydroxylysine was partially purified from rat kidney cortex by means of acid precipitation and DEAE-Sephadex A-50 column chromatography. The enzyme activity was assayed by measuring the transfer of [32P] from gamma-[32P]-GTP to materials not adsorbed by charcoal. This partially purified enzyme showed essentially no GTP phosphohydrolase activity and an optimal pH of 8.0. An apparent Km of about 23.8 mumol/1 was obtained with respect to 5-hydroxylysine. Mg2+ was required for the activity of this enzyme. Ethanolamine, L-lysine, L-ornithine and choline inhibited the enzyme but L-threonine, L-serine and hydroxy-L-proline did not. None of these compounds severed as substrate for this enzyme."}
{"id": "PMID:18340", "title": "Isatin enzyme interactions. V. Activation of rat liver acid phosphatase.", "content": "Influence of Isatin on rat tissue acid phosphatase has been studied. It has an organ-specific effect, the liver enzyme is activated, the brain enzyme is inhibited while those of kidney and intestine are not affected. Isatin activation of the liver enzyme is of mixed type and pH dependent. Rat liver enzyme appears to require intact amino and sulfhydryl groups for activity. Isatin seems to combine with the enzyme through the sulfhydryl group of the latter.", "contents": "Isatin enzyme interactions. V. Activation of rat liver acid phosphatase. Influence of Isatin on rat tissue acid phosphatase has been studied. It has an organ-specific effect, the liver enzyme is activated, the brain enzyme is inhibited while those of kidney and intestine are not affected. Isatin activation of the liver enzyme is of mixed type and pH dependent. Rat liver enzyme appears to require intact amino and sulfhydryl groups for activity. Isatin seems to combine with the enzyme through the sulfhydryl group of the latter."}
{"id": "PMID:18341", "title": "Effect of cofactor depletion on liver tyrosine aminotransferase expression.", "content": "Hepatic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from pyridoxine depleted and control rats and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gel. Six enzymatically active forms were detected. Cofactor depletion effected further resolution of the enzyme into seven active forms as revealed by the bifurcation of the major active peak.", "contents": "Effect of cofactor depletion on liver tyrosine aminotransferase expression. Hepatic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from pyridoxine depleted and control rats and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gel. Six enzymatically active forms were detected. Cofactor depletion effected further resolution of the enzyme into seven active forms as revealed by the bifurcation of the major active peak."}
{"id": "PMID:18342", "title": "Interactions of citrate synthases from osmoconforming and osmoregulating animals with salt: possible signs of molecular eco-adaptation?", "content": "This study considers differential sensitivity of citrate synthase (citrate oxaloacetatelyase [CoA acetylating]) EC 4.1.3.7. from an osmoconforming animal (sea anemone) and an osmoregulating animal (the pig) to salt. Attention is drawn to the fact that the osmoconforming sea anemone is in essence a sessile creature while the pig is readily mobile and able to change its ionic environment at will. It had been shown earlier that citrate synthase from another osmoconformer (oyster) is also not sensitive to ionic strength while citrate synthase from osmoregulating white shrimp is sensitive to increasing levels of salt. However, these enzymes are characteristically regulated by ATP and alpha-ketoglutarate. Both forms of citrate synthase are denatured by 6 M guanidine hydrochloride and are aided by salt levels in their refolding but the rate and extent of refolding of the osmoconformer citrate synthase are greater than those of the osmoregulator citrate synthase. Catalytic activity of both forms of citrate synthase is inhibited by incubation in distilled water; osmoconformer citrate synthase was inhibited completely in 7 h while osmoregulator citrate synthase was inhibited only 60% in this time and 80% after 22 h in distilled water. The eco-adaptive and evolutionary implications of these findings are discussed.", "contents": "Interactions of citrate synthases from osmoconforming and osmoregulating animals with salt: possible signs of molecular eco-adaptation? This study considers differential sensitivity of citrate synthase (citrate oxaloacetatelyase [CoA acetylating]) EC 4.1.3.7. from an osmoconforming animal (sea anemone) and an osmoregulating animal (the pig) to salt. Attention is drawn to the fact that the osmoconforming sea anemone is in essence a sessile creature while the pig is readily mobile and able to change its ionic environment at will. It had been shown earlier that citrate synthase from another osmoconformer (oyster) is also not sensitive to ionic strength while citrate synthase from osmoregulating white shrimp is sensitive to increasing levels of salt. However, these enzymes are characteristically regulated by ATP and alpha-ketoglutarate. Both forms of citrate synthase are denatured by 6 M guanidine hydrochloride and are aided by salt levels in their refolding but the rate and extent of refolding of the osmoconformer citrate synthase are greater than those of the osmoregulator citrate synthase. Catalytic activity of both forms of citrate synthase is inhibited by incubation in distilled water; osmoconformer citrate synthase was inhibited completely in 7 h while osmoregulator citrate synthase was inhibited only 60% in this time and 80% after 22 h in distilled water. The eco-adaptive and evolutionary implications of these findings are discussed."}
{"id": "PMID:18343", "title": "A deoxyribonuclease from Chlamydomonas reinhardii. 1. Purification and properties.", "content": "A deoxyribonuclease has been purified more than 2000-fold from the green algae, Chlamydomonas reinhardii. The enzyme is most active on denatured DNA. Optimum activity is at pH 8.5, in 80 mM Tris-HCl buffer and 2 mM CaCl2. Other divalent cations can replace Ca2+ with varying lower efficiency. EDTA and inorganic phosphate are strongly inhibitory, while ATP and high concentrations of 2-mercaptoethanol are slightly inhibitory. The molecular weight is approximately 35 000, the Stokes radius is 2.7 nm, and the sedimentation coefficient 2.8 S. It is a single polypeptide chain, and the frictional ratio of 1.27 suggests it is only slightly asymetrical. The isoelectric point is 9.5. This enzyme has been termed exonuclease 1.", "contents": "A deoxyribonuclease from Chlamydomonas reinhardii. 1. Purification and properties. A deoxyribonuclease has been purified more than 2000-fold from the green algae, Chlamydomonas reinhardii. The enzyme is most active on denatured DNA. Optimum activity is at pH 8.5, in 80 mM Tris-HCl buffer and 2 mM CaCl2. Other divalent cations can replace Ca2+ with varying lower efficiency. EDTA and inorganic phosphate are strongly inhibitory, while ATP and high concentrations of 2-mercaptoethanol are slightly inhibitory. The molecular weight is approximately 35 000, the Stokes radius is 2.7 nm, and the sedimentation coefficient 2.8 S. It is a single polypeptide chain, and the frictional ratio of 1.27 suggests it is only slightly asymetrical. The isoelectric point is 9.5. This enzyme has been termed exonuclease 1."}
{"id": "PMID:18344", "title": "Dihydroxyacetone reductase from Mucor javanicus. 1. Isolation and properties.", "content": "An NADPH-dependent oxidoreductase has been extracted from the mycelium of the fungus Mucor Javanicus (Wehmer) and enriched 1000-fold with respect to the protein contained in the crude extract after centrifugation at 2600 X g. The molecular weight of the enzyme was estimated by gel filtration to be about 100 000; electrophoresis under dissociating conditions indicates four subunits of molecular weight about 28 000. Data on stability and activity of the enzyme as a function of pH and temperature are reported. From a kinetic study and product analysis of the reduction of the two enantiomeric trans-1-decalones and also from a kinetic study of the oxidation of the two diastereomeric pairs of trans-1-decalols it follows that the enzymes is an e-Si oxidoreductase (according to the nomenclature proposed by Dutler et al., Eur. J. Biochem. 22 [1971]203-212 and Prelog and Helmchen, Helv. Chim. Acta, 55 [1972] 2581-2598). This classification is amply confirmed by the kinetic behaviour of a large number of alicyclic substrates. Using (4-2HSi-labelled coenzyme to reduce (9S)-trans-1,4-decalindione, it was shown that the enzyme is HSi (= HS = HB)-stereospecific with respect to the coenzyme. It is demonstrated that the oxidoreductase from Mucor javanicus can be used for the preparation of optically pure chiral alcohols and ketones. In the following paper evidence is presented that the natural substrate of the enzyme is dihydroxyacetone.", "contents": "Dihydroxyacetone reductase from Mucor javanicus. 1. Isolation and properties. An NADPH-dependent oxidoreductase has been extracted from the mycelium of the fungus Mucor Javanicus (Wehmer) and enriched 1000-fold with respect to the protein contained in the crude extract after centrifugation at 2600 X g. The molecular weight of the enzyme was estimated by gel filtration to be about 100 000; electrophoresis under dissociating conditions indicates four subunits of molecular weight about 28 000. Data on stability and activity of the enzyme as a function of pH and temperature are reported. From a kinetic study and product analysis of the reduction of the two enantiomeric trans-1-decalones and also from a kinetic study of the oxidation of the two diastereomeric pairs of trans-1-decalols it follows that the enzymes is an e-Si oxidoreductase (according to the nomenclature proposed by Dutler et al., Eur. J. Biochem. 22 [1971]203-212 and Prelog and Helmchen, Helv. Chim. Acta, 55 [1972] 2581-2598). This classification is amply confirmed by the kinetic behaviour of a large number of alicyclic substrates. Using (4-2HSi-labelled coenzyme to reduce (9S)-trans-1,4-decalindione, it was shown that the enzyme is HSi (= HS = HB)-stereospecific with respect to the coenzyme. It is demonstrated that the oxidoreductase from Mucor javanicus can be used for the preparation of optically pure chiral alcohols and ketones. In the following paper evidence is presented that the natural substrate of the enzyme is dihydroxyacetone."}
{"id": "PMID:18348", "title": "On the structure of flavin-oxygen intermediates involved in enzymatic reactions.", "content": "During the catalytic reactions of flavoprotein hydroxylases and bacterial luciferase, flavin peroxides are formed as intermediates [see Massey, V. and Hemmerich, P. (1976) in The Enzymes, 3rd edn (P. Boyer, ed.) pp. 421--505, Academic Press, New York]. These intermediates have been postulated to be C(4a) derivatives of the flavin coenzyme. To test this hypothesis, modified flavin coenzymes carrying an oxygen substituent at position C(4a) of the isoalloxazine ring were synthesized. They are tightly bound by the apoenzymes of D-amino acid oxidase, p-hydroxybenzoate hydroxylase and lactate oxidase; the resulting complexes show spectral properties closely similar to those of the transient oxygen adducts of the hydroxylases. The optical spectra of the lumiflavin model compounds were found to be highly dependent on the solvent environment and nature of the subsituents. Under appropriate conditions they simulate satisfactorily the spectra of the transient enzymatic oxygen adducts. The results support the proposal that the primary oxygen adducts formed with these flavoproteins on reaction of the reduced enzymes with oxygen are flavin C(4a) peroxides.", "contents": "On the structure of flavin-oxygen intermediates involved in enzymatic reactions. During the catalytic reactions of flavoprotein hydroxylases and bacterial luciferase, flavin peroxides are formed as intermediates [see Massey, V. and Hemmerich, P. (1976) in The Enzymes, 3rd edn (P. Boyer, ed.) pp. 421--505, Academic Press, New York]. These intermediates have been postulated to be C(4a) derivatives of the flavin coenzyme. To test this hypothesis, modified flavin coenzymes carrying an oxygen substituent at position C(4a) of the isoalloxazine ring were synthesized. They are tightly bound by the apoenzymes of D-amino acid oxidase, p-hydroxybenzoate hydroxylase and lactate oxidase; the resulting complexes show spectral properties closely similar to those of the transient oxygen adducts of the hydroxylases. The optical spectra of the lumiflavin model compounds were found to be highly dependent on the solvent environment and nature of the subsituents. Under appropriate conditions they simulate satisfactorily the spectra of the transient enzymatic oxygen adducts. The results support the proposal that the primary oxygen adducts formed with these flavoproteins on reaction of the reduced enzymes with oxygen are flavin C(4a) peroxides."}
{"id": "PMID:18351", "title": "A phosphorus-magnetic-resonance study of the interaction of Mg2+ with adenyl-5'-yl imidodiphosphate. Binding sites of Mg2+ ion on the phosphate chain.", "content": "The interaction of Mg2+ ions with adenyl-5'-yl imidodiphosphate, AMP-P(NH)P, has been studied at basic and acidic pH values by phosphorus magnetic resonance spectroscopy in aqueous solution. The results suggest that Mg2+ binds simultaneously to one (or both) of the two free oxygen atoms of the beta-phosphate moiety and to the nitrogen atom of the phosphate chain (P alpha-O-P beta-N-P gamma). The interaction arises from 1: 1 complexing of Mg2+ to AMP-P(NH)P. The mode of the Mg2+ binding on the phosphate chain remains the same at both basic and acidic pH values. As in the case of ATP and ADP, the association of Mg2+ reduces the pK by about 1.5 units. On the other hand phosphorus titration curves showed that when the phosphate chain does not possess the regular periodicity (O-P alpha-O-P beta-X-P gamma-O,X not equal to O) as in the case of ATP, protonation of the terminal phosphate group may induce a 31P chemical shift variation less important for this group than for the preceding one.", "contents": "A phosphorus-magnetic-resonance study of the interaction of Mg2+ with adenyl-5'-yl imidodiphosphate. Binding sites of Mg2+ ion on the phosphate chain. The interaction of Mg2+ ions with adenyl-5'-yl imidodiphosphate, AMP-P(NH)P, has been studied at basic and acidic pH values by phosphorus magnetic resonance spectroscopy in aqueous solution. The results suggest that Mg2+ binds simultaneously to one (or both) of the two free oxygen atoms of the beta-phosphate moiety and to the nitrogen atom of the phosphate chain (P alpha-O-P beta-N-P gamma). The interaction arises from 1: 1 complexing of Mg2+ to AMP-P(NH)P. The mode of the Mg2+ binding on the phosphate chain remains the same at both basic and acidic pH values. As in the case of ATP and ADP, the association of Mg2+ reduces the pK by about 1.5 units. On the other hand phosphorus titration curves showed that when the phosphate chain does not possess the regular periodicity (O-P alpha-O-P beta-X-P gamma-O,X not equal to O) as in the case of ATP, protonation of the terminal phosphate group may induce a 31P chemical shift variation less important for this group than for the preceding one."}
{"id": "PMID:18352", "title": "Nickel cytochrome c. Effect of protein moiety on the metal ion coordination.", "content": "Nickel cytochrome c has been synthesized by the reaction of metal-free porphyrin cytochrome c with Ni(II) ions in 0.6 Mglycylglycine and 4 M KSCN. Electronic spectra and susceptibility measurement showed the nickel to be in a high-spin octahedral configuration exemplifying the strong influence of the protein moiety as a macrocyclic ligand on the coordination chemistry of the metal ion. Nickel cytochrome c has the same electrophoretic mobility, helicity and pK values of conformational transitions as the native enzyme. At high pH, the partially denatured nickel cytochrome c becomes dimeric. Nitric oxide reacts with nickel cytochrome c to form the nitrosyl derivative with (formula: see text). Reaction of NO with nickel protoporphyrin IX dimethyl ester in toluene, pyridine, or methylthioethanol produced no stable nitrosyl products, clearly demonstrating the effect of protein on metal ion ligation.", "contents": "Nickel cytochrome c. Effect of protein moiety on the metal ion coordination. Nickel cytochrome c has been synthesized by the reaction of metal-free porphyrin cytochrome c with Ni(II) ions in 0.6 Mglycylglycine and 4 M KSCN. Electronic spectra and susceptibility measurement showed the nickel to be in a high-spin octahedral configuration exemplifying the strong influence of the protein moiety as a macrocyclic ligand on the coordination chemistry of the metal ion. Nickel cytochrome c has the same electrophoretic mobility, helicity and pK values of conformational transitions as the native enzyme. At high pH, the partially denatured nickel cytochrome c becomes dimeric. Nitric oxide reacts with nickel cytochrome c to form the nitrosyl derivative with (formula: see text). Reaction of NO with nickel protoporphyrin IX dimethyl ester in toluene, pyridine, or methylthioethanol produced no stable nitrosyl products, clearly demonstrating the effect of protein on metal ion ligation."}
{"id": "PMID:18353", "title": "Anorchi.", "content": "Anorchia was diagnosed in 3 patients after a hormonal study entailing the basic determination of FSH, LH and testosterone by a radioimmunoassay technique and by later stimulation with HCG. 2,000 IU are administered during 3 consecutive days with a new testosterone determination 24 and 72 h after the last administration. If the result is negative, the test is repeated but the HCG dose is doubled. A new negative response confirms the diagnosis of anorchia. If the results are positive a spermatic phlebography allows localization of the testicles or the remains of Wolffian origin in order to simplify surgery.", "contents": "Anorchi. Anorchia was diagnosed in 3 patients after a hormonal study entailing the basic determination of FSH, LH and testosterone by a radioimmunoassay technique and by later stimulation with HCG. 2,000 IU are administered during 3 consecutive days with a new testosterone determination 24 and 72 h after the last administration. If the result is negative, the test is repeated but the HCG dose is doubled. A new negative response confirms the diagnosis of anorchia. If the results are positive a spermatic phlebography allows localization of the testicles or the remains of Wolffian origin in order to simplify surgery."}
{"id": "PMID:18354", "title": "Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats.", "content": "The activities of monoamine biosynthetic enzymes were measured in brain regions of several hypertensive rat models at various ages. The types of hypertensive rats were the spontaneously hypertensive rat (SHR) and a stroke-prone substrain of the SHR as well as DOCA-salt and renal hypertensive rats. The genetically hypertensive rats had significantly elevated blood pressures as compared to the Wistar-Kyoto control rat after 5 weeks of age. During the early development of hypertension in the SHR, the activities of tyrosine hydroxylase in the hypothalamus and corpus striatum and of dopamine-beta-hydroxylase in the hypothalamus and pons-medulla were significantly higher than in the control rats. Tryptophan-hydroxylase was also elevated in the hypothalamus in SHR. From 3 to 8 weeks of age there appeared to be a significant correlation between hypothalamic dopamine-beta-hydroxylase activity and blood pressure in the hypertensive rats. In contrast, the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were slightly decreased in the DOCA-salt and renal hypertensive rats. It is suggested that noradrenergic or adrenergic neurons in the hypothalamus may participate in the initiation of elevated blood pressure in the genetic, but not in the DOCA-salt or renal hypertensive rats.", "contents": "Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats. The activities of monoamine biosynthetic enzymes were measured in brain regions of several hypertensive rat models at various ages. The types of hypertensive rats were the spontaneously hypertensive rat (SHR) and a stroke-prone substrain of the SHR as well as DOCA-salt and renal hypertensive rats. The genetically hypertensive rats had significantly elevated blood pressures as compared to the Wistar-Kyoto control rat after 5 weeks of age. During the early development of hypertension in the SHR, the activities of tyrosine hydroxylase in the hypothalamus and corpus striatum and of dopamine-beta-hydroxylase in the hypothalamus and pons-medulla were significantly higher than in the control rats. Tryptophan-hydroxylase was also elevated in the hypothalamus in SHR. From 3 to 8 weeks of age there appeared to be a significant correlation between hypothalamic dopamine-beta-hydroxylase activity and blood pressure in the hypertensive rats. In contrast, the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were slightly decreased in the DOCA-salt and renal hypertensive rats. It is suggested that noradrenergic or adrenergic neurons in the hypothalamus may participate in the initiation of elevated blood pressure in the genetic, but not in the DOCA-salt or renal hypertensive rats."}
{"id": "PMID:18355", "title": "Some cardiovascular effects of ST-91 and clonidine.", "content": "St-91, 2(2,6-diethylphenylamino)-2-imidazoline, is a clonidine derivative which does not penetrate the blood-brain barrier. In spontaneously hypertensive (SH) rats is acutely increased arterial pressure and reduced heart rate while at 8 to 12 h after oral administration, it slightly lowered arterial pressure. In contrast, clonidine had acute antihypertensive activity at all doses used. By intracerebroventricular administration to SH rats, both drugs (St-91 and clonidine) reduced arterial pressure and heart rate; in this respect, clonidine was more potent then St-91. Cardiac acceleration induced by low frequency electrical stimulation of right cardiac sympathetic nerves in anesthetized and vagotomized dogs was reduced by St-91 at the same doses by clonidine. Phenoxybenzamine, phentolamine and desipramine antagonized the inhibitory effects of St-91 on electrically induced cardiac acceleration. It was concluded that St-91, like clonidine, stimulates inhibitory alpha-adrenergic receptors at the sympathetic nerve endings but, unlike clonidine, is substantially devoid of acute antihypertensive activity. This suggests that stimulation of peripheral presynaptic inhibitory alpha-adrenergic receptors is not likely to represent the sole mechanism of antihypertensive action of clonidine.", "contents": "Some cardiovascular effects of ST-91 and clonidine. St-91, 2(2,6-diethylphenylamino)-2-imidazoline, is a clonidine derivative which does not penetrate the blood-brain barrier. In spontaneously hypertensive (SH) rats is acutely increased arterial pressure and reduced heart rate while at 8 to 12 h after oral administration, it slightly lowered arterial pressure. In contrast, clonidine had acute antihypertensive activity at all doses used. By intracerebroventricular administration to SH rats, both drugs (St-91 and clonidine) reduced arterial pressure and heart rate; in this respect, clonidine was more potent then St-91. Cardiac acceleration induced by low frequency electrical stimulation of right cardiac sympathetic nerves in anesthetized and vagotomized dogs was reduced by St-91 at the same doses by clonidine. Phenoxybenzamine, phentolamine and desipramine antagonized the inhibitory effects of St-91 on electrically induced cardiac acceleration. It was concluded that St-91, like clonidine, stimulates inhibitory alpha-adrenergic receptors at the sympathetic nerve endings but, unlike clonidine, is substantially devoid of acute antihypertensive activity. This suggests that stimulation of peripheral presynaptic inhibitory alpha-adrenergic receptors is not likely to represent the sole mechanism of antihypertensive action of clonidine."}
{"id": "PMID:18356", "title": "Specific alpha-adrenoceptor blocking effect of droperidol on isolated smooth muscles.", "content": "The present study was conducted so as to obtain more insight into the controversies concerning the alpha-adrenoceptor blocking properties of droperidol, a short-acting neuroleptic agent used in neuroleptanalgesia. The effect of droperidol on the vasoconstriction induced by norepinephrine, sympathetic nerve stimulation, histamine and potassium ions was studied on isolated, perfused ear arteries; its effect on norepinephrine-induced contraction was studied on isolated aorta, spleen and vas deferens. In addition, the onset and duration of action of droperidol was studied. Low doses of droperidol inhibit the vasoconstriction induced by norepinephrine and sympathetic nerve stimulation in the ear artery of the rabbit (3.3 X 10(-9) M and 1.3 X 10(-8) M respectively). At similar low doses, droperidol inhibits norepinephrine-induced contractions in the other tissues studied and has a potency comparable to that of phentolamine; its action is rapid in onset and of short duration. High doses of droperidol (10(-6) M) also inhibit the vasoconstriction of the ear artery induced by histamine and by potassium ions. These findings indicate that a low doses, droperidol has specific and competitive alpha-adrenoceptor blocking effects.", "contents": "Specific alpha-adrenoceptor blocking effect of droperidol on isolated smooth muscles. The present study was conducted so as to obtain more insight into the controversies concerning the alpha-adrenoceptor blocking properties of droperidol, a short-acting neuroleptic agent used in neuroleptanalgesia. The effect of droperidol on the vasoconstriction induced by norepinephrine, sympathetic nerve stimulation, histamine and potassium ions was studied on isolated, perfused ear arteries; its effect on norepinephrine-induced contraction was studied on isolated aorta, spleen and vas deferens. In addition, the onset and duration of action of droperidol was studied. Low doses of droperidol inhibit the vasoconstriction induced by norepinephrine and sympathetic nerve stimulation in the ear artery of the rabbit (3.3 X 10(-9) M and 1.3 X 10(-8) M respectively). At similar low doses, droperidol inhibits norepinephrine-induced contractions in the other tissues studied and has a potency comparable to that of phentolamine; its action is rapid in onset and of short duration. High doses of droperidol (10(-6) M) also inhibit the vasoconstriction of the ear artery induced by histamine and by potassium ions. These findings indicate that a low doses, droperidol has specific and competitive alpha-adrenoceptor blocking effects."}
{"id": "PMID:18357", "title": "Withdrawal syndrome upon cessation of chronic clonidine treatment in rats.", "content": "Clinical reports indicate that cessation of treatment with the antihypertensive agent clonidine is associated with a withdrawal syndrome which may include a hypertensive overshoot of critical proportions. We have attempted to produce an animal model of this syndrome in rats. Rats were treated with clonidine in the drinking water (5 microgram/ml; total dose 300-500 microgram/kg/day) which produced a significant (approx. 20%) decrease in heart rate and blood pressure. Within 24 h of cessation of treatment a significantly greater (approximately 100 beats/min) heart rate was seen in treated animals than in control animals when measurements were made in conscious animals. No hypertensive overshoot was observed. Cessation of treatment was associated with an increase in sympatho-adrenal tone as shown by a trans-synaptic induction of adrenal tyrosine hydroxylase activity. Adrenal denervation prevented the rise in adrenal tyrosine hydroxylase seen after cessation of treatment. Administration of clonidine to pregnant rats (10th day until term) did not alter the development of adrenal tyrosine hydroxylase in the offspring. The data indicate that a withdrawal syndrome is produced upon cessation of chronic clonidine treatment.", "contents": "Withdrawal syndrome upon cessation of chronic clonidine treatment in rats. Clinical reports indicate that cessation of treatment with the antihypertensive agent clonidine is associated with a withdrawal syndrome which may include a hypertensive overshoot of critical proportions. We have attempted to produce an animal model of this syndrome in rats. Rats were treated with clonidine in the drinking water (5 microgram/ml; total dose 300-500 microgram/kg/day) which produced a significant (approx. 20%) decrease in heart rate and blood pressure. Within 24 h of cessation of treatment a significantly greater (approximately 100 beats/min) heart rate was seen in treated animals than in control animals when measurements were made in conscious animals. No hypertensive overshoot was observed. Cessation of treatment was associated with an increase in sympatho-adrenal tone as shown by a trans-synaptic induction of adrenal tyrosine hydroxylase activity. Adrenal denervation prevented the rise in adrenal tyrosine hydroxylase seen after cessation of treatment. Administration of clonidine to pregnant rats (10th day until term) did not alter the development of adrenal tyrosine hydroxylase in the offspring. The data indicate that a withdrawal syndrome is produced upon cessation of chronic clonidine treatment."}
{"id": "PMID:18366", "title": "[Effect of various analeptics on the outcome of acute microwave lesion in mice].", "content": "The survival of albino mice irradiated by microwaves till the terminal state (wave length of 12.5 cm, intensity-62 +/- 5 microvat, for 14-16 minutes), given directly after irradiation diethylamide of nicotinic acid (cordiamine) in a dose of 50 mg/kg intraperitoneally and strychnine nitrate in a dose of 1 mg/kg, subcutaneously, i. e. nearly 1.5 times as much as received by controls, was studied. The application of caffeine sodium benzoate, camphor, metrasol, lobeline hydrochloride and cytisine, employed in different doses, proved to be little effective.", "contents": "[Effect of various analeptics on the outcome of acute microwave lesion in mice]. The survival of albino mice irradiated by microwaves till the terminal state (wave length of 12.5 cm, intensity-62 +/- 5 microvat, for 14-16 minutes), given directly after irradiation diethylamide of nicotinic acid (cordiamine) in a dose of 50 mg/kg intraperitoneally and strychnine nitrate in a dose of 1 mg/kg, subcutaneously, i. e. nearly 1.5 times as much as received by controls, was studied. The application of caffeine sodium benzoate, camphor, metrasol, lobeline hydrochloride and cytisine, employed in different doses, proved to be little effective."}
{"id": "PMID:18370", "title": "[Effect of corticotropin on functional and metabolic processes in muscles].", "content": "Changes of excitability, contractility, temperature, activity of oxydation-reduction enzymes, pyridine nucleotides, and of free fatty acids were studied in m. m. gastrocnemii of rabbits and rats during activity, after administration of 1 unit per 100 g of corticotropin (ACTH). Within 30 min after administration, the ACTH did not alter the excitability of a neural-muscular system but increased its efficiency by means of stimulation of the free fatty acids usage. Besides, the ACTH elicits no regular changes of the oxydation--reduction enzymes activity during a short-lasting muscular activity. Its regulating effect on the metabolic processes in muscles is realised at the level of anaerobic processes.", "contents": "[Effect of corticotropin on functional and metabolic processes in muscles]. Changes of excitability, contractility, temperature, activity of oxydation-reduction enzymes, pyridine nucleotides, and of free fatty acids were studied in m. m. gastrocnemii of rabbits and rats during activity, after administration of 1 unit per 100 g of corticotropin (ACTH). Within 30 min after administration, the ACTH did not alter the excitability of a neural-muscular system but increased its efficiency by means of stimulation of the free fatty acids usage. Besides, the ACTH elicits no regular changes of the oxydation--reduction enzymes activity during a short-lasting muscular activity. Its regulating effect on the metabolic processes in muscles is realised at the level of anaerobic processes."}
{"id": "PMID:18367", "title": "[Relationship between the pain-relieving action of narcotic analgesics and their effect on respiration].", "content": "Experiments with rabbits (30) and albino rats (110) demonstrated that morphine (1 mg/kg), promedol (trimeperidine) (2 mg/kg) and phentanyl (0.02 mg/kg), while raising by 21-24 per cent of the algesia threshold, produced an analgesic effect differeing in its duration (morphine-130 min, trimeperidine-70 min, phentanyl-17 min). This is attended by changes in respiration (greater on introduction of phentanyl, and lesser, following administration of morphine) and by shifts in the functional state of the tissues (greater on introduction of trimeperidine and lesser after aministration of morphine).", "contents": "[Relationship between the pain-relieving action of narcotic analgesics and their effect on respiration]. Experiments with rabbits (30) and albino rats (110) demonstrated that morphine (1 mg/kg), promedol (trimeperidine) (2 mg/kg) and phentanyl (0.02 mg/kg), while raising by 21-24 per cent of the algesia threshold, produced an analgesic effect differeing in its duration (morphine-130 min, trimeperidine-70 min, phentanyl-17 min). This is attended by changes in respiration (greater on introduction of phentanyl, and lesser, following administration of morphine) and by shifts in the functional state of the tissues (greater on introduction of trimeperidine and lesser after aministration of morphine)."}
{"id": "PMID:18371", "title": "Nucleolar and functional characterization of lymphocytes following cyclophosphamide treatment.", "content": "Profound lymphocyte depletion occurs in thymus, lymph nodes and spleens of normal and thymectomized mice early after a single high sublethal dose of cyclophosphamide. Among individual lymphocytes characterized by the different types of nucleolus, the \"non-activable\" lymphocytes with micronucleoli are affected most markedly by CY, whereas the proportion of the \"active\" lymphocytes is increased (up to 70% in the spleens). During the period of regeneration lymphocytes with micronucleoli increase rapidly, the increment thereof is very high on day 14 in the spleens of all mice, and still higher in the blood and lymph nodes of thymectomized animals. During the period of lymphocytopenia, in spite of the increased proportion of the \"active\" lymphocytes, the ability of residual cells of elicit GVH reactions and to incorporate 14C-uridine decreases. In contrast to changes in the early period, the recovery of the \"active\" lymphocytes and GVH reactivity, which is still incomplete on day 14, depends on the presence of an intact thymus.", "contents": "Nucleolar and functional characterization of lymphocytes following cyclophosphamide treatment. Profound lymphocyte depletion occurs in thymus, lymph nodes and spleens of normal and thymectomized mice early after a single high sublethal dose of cyclophosphamide. Among individual lymphocytes characterized by the different types of nucleolus, the \"non-activable\" lymphocytes with micronucleoli are affected most markedly by CY, whereas the proportion of the \"active\" lymphocytes is increased (up to 70% in the spleens). During the period of regeneration lymphocytes with micronucleoli increase rapidly, the increment thereof is very high on day 14 in the spleens of all mice, and still higher in the blood and lymph nodes of thymectomized animals. During the period of lymphocytopenia, in spite of the increased proportion of the \"active\" lymphocytes, the ability of residual cells of elicit GVH reactions and to incorporate 14C-uridine decreases. In contrast to changes in the early period, the recovery of the \"active\" lymphocytes and GVH reactivity, which is still incomplete on day 14, depends on the presence of an intact thymus."}
{"id": "PMID:18374", "title": "Evidence for improved cardiac performance after beta-blockade in patients with coronary artery disease.", "content": "The study was undertaken to investigate the acute haemodynamic effects of bunitrolol (0-2-hydroxy-3-(tert.butylamino)-propoxy)-bity. Right and left heart catheterization was performed in eleven patients with documented coronary artery disease. After bunitrolol (10 mg i.v.), there was a statistically significant decrease in left ventricular and aortic systolic pressures left ventricular end-diastolic pressure, aortic diastolic and mean pressures, pressure-rate product and compliance index (delta P/delta V).  Left ventricular dp/dt, left ventricular dp/dt over isovolumic pressure, systemic resistance and heart rate tended to decrease, stroke volume and left ventricular stroke work index tended to increase, without statistical significance. Cardiac index showed individual variations, the mean values for the group being unchanged. Correlation of left ventricular end-diastolic pressure and left ventricular stroke work index showed a shift toward improved ventricular function curve in most cases, deterioration in no instance. Supine exercise was performed in ten patients. Angina occurred in nine patients; in five only before and in four before and after beta-blockade. Post-drug exercise heart rate, pressure-rate product and left ventricular end-diastolic pressure were significantly lower, the latter also in the four patients who still presented exercise angina. It is concluded that certain beta-blockers can improve cardiac performance at rest and during exercise in patients with coronary artery disease. This is explainable on the basis of a more favourable balance between oxygen supply and demand, together with a less marked negative inotropic effect due to the partial agonist activity of the agent used in the study.", "contents": "Evidence for improved cardiac performance after beta-blockade in patients with coronary artery disease. The study was undertaken to investigate the acute haemodynamic effects of bunitrolol (0-2-hydroxy-3-(tert.butylamino)-propoxy)-bity. Right and left heart catheterization was performed in eleven patients with documented coronary artery disease. After bunitrolol (10 mg i.v.), there was a statistically significant decrease in left ventricular and aortic systolic pressures left ventricular end-diastolic pressure, aortic diastolic and mean pressures, pressure-rate product and compliance index (delta P/delta V).  Left ventricular dp/dt, left ventricular dp/dt over isovolumic pressure, systemic resistance and heart rate tended to decrease, stroke volume and left ventricular stroke work index tended to increase, without statistical significance. Cardiac index showed individual variations, the mean values for the group being unchanged. Correlation of left ventricular end-diastolic pressure and left ventricular stroke work index showed a shift toward improved ventricular function curve in most cases, deterioration in no instance. Supine exercise was performed in ten patients. Angina occurred in nine patients; in five only before and in four before and after beta-blockade. Post-drug exercise heart rate, pressure-rate product and left ventricular end-diastolic pressure were significantly lower, the latter also in the four patients who still presented exercise angina. It is concluded that certain beta-blockers can improve cardiac performance at rest and during exercise in patients with coronary artery disease. This is explainable on the basis of a more favourable balance between oxygen supply and demand, together with a less marked negative inotropic effect due to the partial agonist activity of the agent used in the study."}
{"id": "PMID:18375", "title": "The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice.", "content": "A twelve-week study involving fifty-three patients is described as taking place in a practice with a higher than average geriatric population. The purpose of the study was to substitute flurazepam for habitually used barbiturates or methaqualone/diphenhydramine. Of the original fifty-three patients admitted to the study, fifty-one completed; the two drop-outs resulting from concomitant physical illness. Eighty-four per cent of patients were successfully changed to flurazepam. Of those who did not accept flurazepam, eight per cent accepted nitrazepam, while six per cent of patients were motivated to stop all hypnotics. During the three month period of the study none of the well-known disadvantages of the barbiturates and methaqualone/diphenhydramine were seen with flurazepam. The author found flurazepam to be a very efficient hypnotic of relatively low toxicity which could be easily substituted fro barbiturates and methaqualone/diphenhydramine in the treatment of long-term insomnia.", "contents": "The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice. A twelve-week study involving fifty-three patients is described as taking place in a practice with a higher than average geriatric population. The purpose of the study was to substitute flurazepam for habitually used barbiturates or methaqualone/diphenhydramine. Of the original fifty-three patients admitted to the study, fifty-one completed; the two drop-outs resulting from concomitant physical illness. Eighty-four per cent of patients were successfully changed to flurazepam. Of those who did not accept flurazepam, eight per cent accepted nitrazepam, while six per cent of patients were motivated to stop all hypnotics. During the three month period of the study none of the well-known disadvantages of the barbiturates and methaqualone/diphenhydramine were seen with flurazepam. The author found flurazepam to be a very efficient hypnotic of relatively low toxicity which could be easily substituted fro barbiturates and methaqualone/diphenhydramine in the treatment of long-term insomnia."}
{"id": "PMID:18376", "title": "A trial of benorylate tablets in the symptomatic relief of osteoarthritis.", "content": "A two-week assessment of Benoral tablets was carried out in general practice in 171 patients with degenerative joint disease to see how symptomatic response related to selected presenting features of the disease. A short history, less severe initial state and multiple joint involvement were each associated with a better response. Overall 84-4% of patients reported Benoral tablets to have helped relieve their symptoms and a high proportion preferred Benoral to their previous anti-arthritic medication.", "contents": "A trial of benorylate tablets in the symptomatic relief of osteoarthritis. A two-week assessment of Benoral tablets was carried out in general practice in 171 patients with degenerative joint disease to see how symptomatic response related to selected presenting features of the disease. A short history, less severe initial state and multiple joint involvement were each associated with a better response. Overall 84-4% of patients reported Benoral tablets to have helped relieve their symptoms and a high proportion preferred Benoral to their previous anti-arthritic medication."}
{"id": "PMID:18377", "title": "Temperature dependence of adenylate cyclase activity from rat white adipocytes.", "content": "The effects of temperature on adenylate cyclase (AC) activity from rat white adipocytes were studied. Arrhenius plots of the data were found to be biphasic for basal AC activity, with a break near 27 degrees C. Noradrenaline and corticotropin induced a shift in the break with a rise in energy of activation (Ea) on both sides of the break. Aabove break point only, Ea increased with respect to hormone does as a hyperbolic function. The maximum value was in the range 17-21 Kcal x mol-1. Temperature was shown to have only a slight effect on the binding capacity of corticotropin to its receptor sites. The possibility of the existence of multiple thermodynamic states for the enzyme is envisaged. Basal AC activity is thermodynamically different from the hormone-stimulated enzyme. Hormones induce changes in the basal conformation of the enzyme, and this is reflected in modifications of Arrhenius plots. The maximal state of activation reached with high doses of hormones could be interpreted as a 'desensitization' of enzyme and/or enzyme systems to membrane lipid interactions.", "contents": "Temperature dependence of adenylate cyclase activity from rat white adipocytes. The effects of temperature on adenylate cyclase (AC) activity from rat white adipocytes were studied. Arrhenius plots of the data were found to be biphasic for basal AC activity, with a break near 27 degrees C. Noradrenaline and corticotropin induced a shift in the break with a rise in energy of activation (Ea) on both sides of the break. Aabove break point only, Ea increased with respect to hormone does as a hyperbolic function. The maximum value was in the range 17-21 Kcal x mol-1. Temperature was shown to have only a slight effect on the binding capacity of corticotropin to its receptor sites. The possibility of the existence of multiple thermodynamic states for the enzyme is envisaged. Basal AC activity is thermodynamically different from the hormone-stimulated enzyme. Hormones induce changes in the basal conformation of the enzyme, and this is reflected in modifications of Arrhenius plots. The maximal state of activation reached with high doses of hormones could be interpreted as a 'desensitization' of enzyme and/or enzyme systems to membrane lipid interactions."}
{"id": "PMID:18380", "title": "Amino acid replacements resulting from suppression and missense reversion of a chain-terminator mutation in Neurospora.", "content": "The Neurospora crassa super-suppressor mutation, ssu-1, suppresses the auxotrophic phenotype of the mutant am(17) by inserting tyrosine at residue 313 of NADP-specific glutamate dehydrogenase, a position occupied in the wild type by glutamate. Two classes of am(17) revertants due to further mutation within the am gene have, respectively, tyrosine and leucine at residue 313. These replacements are consistent with a chain-terminating codon in am(17) of either the amber (UAG) or the ochre type (UAA), but are inconsistent with UGA. The Leu313 and Tyr313 variants of the enzyme have effective activity but are grossly different from the wild type in Michaelis constants (especially for ammonium) and heat stabilities at two different pH values. They show smaller but significant differences in these respects from each other.", "contents": "Amino acid replacements resulting from suppression and missense reversion of a chain-terminator mutation in Neurospora. The Neurospora crassa super-suppressor mutation, ssu-1, suppresses the auxotrophic phenotype of the mutant am(17) by inserting tyrosine at residue 313 of NADP-specific glutamate dehydrogenase, a position occupied in the wild type by glutamate. Two classes of am(17) revertants due to further mutation within the am gene have, respectively, tyrosine and leucine at residue 313. These replacements are consistent with a chain-terminating codon in am(17) of either the amber (UAG) or the ochre type (UAA), but are inconsistent with UGA. The Leu313 and Tyr313 variants of the enzyme have effective activity but are grossly different from the wild type in Michaelis constants (especially for ammonium) and heat stabilities at two different pH values. They show smaller but significant differences in these respects from each other."}
{"id": "PMID:18381", "title": "Qualitative changes in fibrinogen following exposure to agents used for preparation of fibrin monomers.", "content": "The solubility, clottability, thrombin clotting time and agarose gel chromatography pattern of human fibrinogen were studied after exposure to solvents commonly used to prepare fibrin monomers (0.0167 M acetic acid with 2.5 mM EDTA; 1 M NaBr, pH 5.2; 3.3 M urea, pH 7.4; 5 M urea, pH 7.4). When exposed to acetic acid at room temperature, fibrinogen precipitated almost immediately and quantitatively. Subsequent dialysis for 72 h against 0.3 M NaCl, pH 7.4, caused resolution of fibrinogen to a varying degree, the amount depending on the time of exposure. The redissolved fibrinogen showed reduced clottability, markedly shortened thrombin clotting time and a chromatographic profile that indicated large amounts of aggregates. Fibrinogen exposed to 1 M NaBr, pH 5.2, at room temperature for 1 h showed a slightly shortened thrombin clotting time and a broadened chromatographic profile. Exposure for 24 h to the same agent resulted in reduced solubility and clottability, a prolonged thrombin clotting time and progressive broadening of the chromatographic profile. Similar findings were obtained with fibrinogen exposed to 5 M urea, pH 7.4. Exposure to 3.3 M urea at pH 7.4 for 24 h, room temperature, led only to a moderate increase in solubility.", "contents": "Qualitative changes in fibrinogen following exposure to agents used for preparation of fibrin monomers. The solubility, clottability, thrombin clotting time and agarose gel chromatography pattern of human fibrinogen were studied after exposure to solvents commonly used to prepare fibrin monomers (0.0167 M acetic acid with 2.5 mM EDTA; 1 M NaBr, pH 5.2; 3.3 M urea, pH 7.4; 5 M urea, pH 7.4). When exposed to acetic acid at room temperature, fibrinogen precipitated almost immediately and quantitatively. Subsequent dialysis for 72 h against 0.3 M NaCl, pH 7.4, caused resolution of fibrinogen to a varying degree, the amount depending on the time of exposure. The redissolved fibrinogen showed reduced clottability, markedly shortened thrombin clotting time and a chromatographic profile that indicated large amounts of aggregates. Fibrinogen exposed to 1 M NaBr, pH 5.2, at room temperature for 1 h showed a slightly shortened thrombin clotting time and a broadened chromatographic profile. Exposure for 24 h to the same agent resulted in reduced solubility and clottability, a prolonged thrombin clotting time and progressive broadening of the chromatographic profile. Similar findings were obtained with fibrinogen exposed to 5 M urea, pH 7.4. Exposure to 3.3 M urea at pH 7.4 for 24 h, room temperature, led only to a moderate increase in solubility."}
{"id": "PMID:18382", "title": "Ditazole and platelets. II. Effect of ditazole on in vivo platelet aggregation and bleeding time in rats.", "content": "Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) is a new drug shown to inhibit prostaglandin release from rat platelets. The present study indicates that ditazole, at doses similar to those inhibiting prostaglandin formation in rat, inhibits in vivo collagen--but not ADP-induced rat platelet aggregation. In addition, ditazole does not prolong the bleeding time in rats, but even tends to shorten it. This effect could be due to the inhibition of prostaglandin formation at the side of the vascular injury produced to induce bleeding.", "contents": "Ditazole and platelets. II. Effect of ditazole on in vivo platelet aggregation and bleeding time in rats. Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) is a new drug shown to inhibit prostaglandin release from rat platelets. The present study indicates that ditazole, at doses similar to those inhibiting prostaglandin formation in rat, inhibits in vivo collagen--but not ADP-induced rat platelet aggregation. In addition, ditazole does not prolong the bleeding time in rats, but even tends to shorten it. This effect could be due to the inhibition of prostaglandin formation at the side of the vascular injury produced to induce bleeding."}
{"id": "PMID:18383", "title": "Reduction of nitro-BT by some components of the chloroform-methanol extract of the grey matter of the rat brain.", "content": "An attempt was made to extract the substance present in the nerve fibres of the cerebral cortex and basal ganglia which reduced Nitro-BT in alkaline medium pH 9-5 [4,5]. The investigations were performed on 40 white Wistar rats of both sexes and ca. 200 g of body weight. The brains taken for studies were fixed in Baker's formalin for 1,5 hr, thereafter grinded and homogenized in chloroform-methanol solution supplemented up to 100 ml of final volume after homogenisation. Thus prepared solution was left for 24 hr at 4 degrees C temperature and than centrifuged 2000 g/min. The extract was evaporated and the sediment further investigated. The following fraction were received: 1. fraction soluble in aceton, 2. fraction soluble in ethylalcohol, 3. fraction soluble in ether, 4. fraction soluble in water and 5. the sediment. Each fraction was incubated with a standard medium containing Nitro-BT. After incubation the amount of reduced Nitro-BT in each of the incubation medium was spectrophotometrically measured. The most intense reduction was found in the incubation medium with the water fraction. The spectrophotometrically determined reduction of Nitro-BT of the water fraction compared with that of the gangliosides solution were similar. The addition into the incubation media biogenic amines and N,N-diethyl-p-phenylenediamine enhances the reduction of Nitro-BT significantly. According to the results obtained an interference of gangliosides and of the investigated amines in the reduction of Nitro-BT is suggested.", "contents": "Reduction of nitro-BT by some components of the chloroform-methanol extract of the grey matter of the rat brain. An attempt was made to extract the substance present in the nerve fibres of the cerebral cortex and basal ganglia which reduced Nitro-BT in alkaline medium pH 9-5 [4,5]. The investigations were performed on 40 white Wistar rats of both sexes and ca. 200 g of body weight. The brains taken for studies were fixed in Baker's formalin for 1,5 hr, thereafter grinded and homogenized in chloroform-methanol solution supplemented up to 100 ml of final volume after homogenisation. Thus prepared solution was left for 24 hr at 4 degrees C temperature and than centrifuged 2000 g/min. The extract was evaporated and the sediment further investigated. The following fraction were received: 1. fraction soluble in aceton, 2. fraction soluble in ethylalcohol, 3. fraction soluble in ether, 4. fraction soluble in water and 5. the sediment. Each fraction was incubated with a standard medium containing Nitro-BT. After incubation the amount of reduced Nitro-BT in each of the incubation medium was spectrophotometrically measured. The most intense reduction was found in the incubation medium with the water fraction. The spectrophotometrically determined reduction of Nitro-BT of the water fraction compared with that of the gangliosides solution were similar. The addition into the incubation media biogenic amines and N,N-diethyl-p-phenylenediamine enhances the reduction of Nitro-BT significantly. According to the results obtained an interference of gangliosides and of the investigated amines in the reduction of Nitro-BT is suggested."}
{"id": "PMID:18384", "title": "[Simple on-line digital determination of the cardiac action potential and its application].", "content": "A system of digital measuring of the cardiac action potential was constructed in order to measure quickly and accurately the resting potential or maximum diastolic potential, overshoot potential, amplitude, time for 50% repolarization and time for 90% repolarization. This system consists of a dual-beam oscilloscope, a digital voltage meter, a digital interval meter and a simple circuit constructed by operational amplifiers. The measurement of the action potential was achieved by tracing only the resting potential or the maximum diastolic potential and the crest of the action potential on the oscilloscope using another beam. The time for measurement is usually 10-15 sec and errors in measurement were considered to be negligible. This system is considered to be useful for digital measurement of the action potential of various cardiac tissues. This system was applied for observation of effects of bufetolol, an adrenergic beta-receptor blocking drug on the action potential of the dog Purkinje fibres. Bufetolol (10(-5) M) caused a slight depolarization of the maximum diastolic potential, decreased overshoot potential, amplitude and maximum rate of rise, and shortened the time for 50% repolarization of the action potential. Bufetolol (10(-4) M) additionally prolonged the time for 90% repolarization.", "contents": "[Simple on-line digital determination of the cardiac action potential and its application]. A system of digital measuring of the cardiac action potential was constructed in order to measure quickly and accurately the resting potential or maximum diastolic potential, overshoot potential, amplitude, time for 50% repolarization and time for 90% repolarization. This system consists of a dual-beam oscilloscope, a digital voltage meter, a digital interval meter and a simple circuit constructed by operational amplifiers. The measurement of the action potential was achieved by tracing only the resting potential or the maximum diastolic potential and the crest of the action potential on the oscilloscope using another beam. The time for measurement is usually 10-15 sec and errors in measurement were considered to be negligible. This system is considered to be useful for digital measurement of the action potential of various cardiac tissues. This system was applied for observation of effects of bufetolol, an adrenergic beta-receptor blocking drug on the action potential of the dog Purkinje fibres. Bufetolol (10(-5) M) caused a slight depolarization of the maximum diastolic potential, decreased overshoot potential, amplitude and maximum rate of rise, and shortened the time for 50% repolarization of the action potential. Bufetolol (10(-4) M) additionally prolonged the time for 90% repolarization."}
{"id": "PMID:18385", "title": "Phosphate uptake and involvement of binding protein in Tween-80 supplemented culture of Aspergillus fumigatus.", "content": "Tween-80 supplementation in submerged culture of Aspergillus fumigatus resulted in an increase of phosphate uptake. The uptake system was characterized as saturable, energy-dependent and operating against the concentration gradient. Control and Tween 80 cultures showed similar Km values for phosphate uptake (50 micrometer). Cold osmotic shock treatment of the cultures was found to cause considerable reduction in the ability to take up phosphorus with concomitant release of the binding protein into the shock fluid. Binding protein preparation from Tween-80 supplemented cells showed more activity than that from control cells.", "contents": "Phosphate uptake and involvement of binding protein in Tween-80 supplemented culture of Aspergillus fumigatus. Tween-80 supplementation in submerged culture of Aspergillus fumigatus resulted in an increase of phosphate uptake. The uptake system was characterized as saturable, energy-dependent and operating against the concentration gradient. Control and Tween 80 cultures showed similar Km values for phosphate uptake (50 micrometer). Cold osmotic shock treatment of the cultures was found to cause considerable reduction in the ability to take up phosphorus with concomitant release of the binding protein into the shock fluid. Binding protein preparation from Tween-80 supplemented cells showed more activity than that from control cells."}
{"id": "PMID:18386", "title": "Variation in age at puberty in monkeys.", "content": "5 female and 3 male patas monkeys and 6 female and 3 male talapoin monkeys matured in a captive breeding colony. Age at puberty is given, and some variation discussed. The talapoin, a very small monkey, becomes adult at 4 1/2 years for females, 1 or 2 years later for males. The patas, a rather large monkey, becomes adult at 2 1/2 years, for females, and 1 or 2 years later for males. Both these ages for puberty differ from data for the rhesus monkey which has been accepted as generalizable to all Old World monkeys. Possible causes of differences between species in average age at puberty are discussed, including nutrition, environmental inconstancy, and relative size of infant and mother. It is suggested that age at first conception, a biologically more relevant index than menarche, should be considered as a potentially important adaptive variable when describing primate species.", "contents": "Variation in age at puberty in monkeys. 5 female and 3 male patas monkeys and 6 female and 3 male talapoin monkeys matured in a captive breeding colony. Age at puberty is given, and some variation discussed. The talapoin, a very small monkey, becomes adult at 4 1/2 years for females, 1 or 2 years later for males. The patas, a rather large monkey, becomes adult at 2 1/2 years, for females, and 1 or 2 years later for males. Both these ages for puberty differ from data for the rhesus monkey which has been accepted as generalizable to all Old World monkeys. Possible causes of differences between species in average age at puberty are discussed, including nutrition, environmental inconstancy, and relative size of infant and mother. It is suggested that age at first conception, a biologically more relevant index than menarche, should be considered as a potentially important adaptive variable when describing primate species."}
{"id": "PMID:18388", "title": "[Acupuncture analgesia].", "content": "The possibility of abolishing pain during operations by needling acupuncture points was detected in China 20 years ago. During the last years the Western World showed great interest in this method, which was tested in a great number of surgical operations. Acupuncture was successful, especially when it was introduced by a short conventional anesthesia. Of special importance seems the possible reduction of anesthetic agents. Though the mode of action of acupuncture cannot yet be explained completely, there exist three different hypotheses: Hypnosis and suggestion, neurophysiological and humoral mechanisms. An actual review on experiments concerning these theories is given.", "contents": "[Acupuncture analgesia]. The possibility of abolishing pain during operations by needling acupuncture points was detected in China 20 years ago. During the last years the Western World showed great interest in this method, which was tested in a great number of surgical operations. Acupuncture was successful, especially when it was introduced by a short conventional anesthesia. Of special importance seems the possible reduction of anesthetic agents. Though the mode of action of acupuncture cannot yet be explained completely, there exist three different hypotheses: Hypnosis and suggestion, neurophysiological and humoral mechanisms. An actual review on experiments concerning these theories is given."}
{"id": "PMID:18389", "title": "[Treatment of concommitant depression in neurologic diseases with dibenzepin infusions].", "content": "A definition of concommitant depression is given. The results of infusorial therapy of Dibenzepin in 53 patients with neurological diseases and concommitant depression are reported. In 86% of all cases good or very good results could be obtained. The preparation is excellently suited for this therapy. The necessity of double therapy, namely the therapy of the basic disease as well as the therapy of the depressive syndrome is stressed.", "contents": "[Treatment of concommitant depression in neurologic diseases with dibenzepin infusions]. A definition of concommitant depression is given. The results of infusorial therapy of Dibenzepin in 53 patients with neurological diseases and concommitant depression are reported. In 86% of all cases good or very good results could be obtained. The preparation is excellently suited for this therapy. The necessity of double therapy, namely the therapy of the basic disease as well as the therapy of the depressive syndrome is stressed."}
{"id": "PMID:18390", "title": "[Blood picture in lactate acidosis. Part 2: acid-base equilibrium and lactate].", "content": "A differentiation between lactate emia (lactic acid emia) and lactate acidosis (lactic acidosis) is made. The normal value for blood lactate concentration is 1-2 mmol/1. The term lactate emia is used for lactate values between 2-6 mmol/1. The limiting value for the diagnosis of lactate acidosis should be more than 7-8 mmol/1 for the blood lactate concentration. Furthermore the different buffer mechanisms are evaluated in respect to their influence on the pH of the blood and to lactate metabolism. Especially the mechanism of respiratory compensation for metabolic acidosis is discussed. It is stated that for the diagnosis of lactate acidosis the blood-pH and the bicarbonate concentration should be measured.", "contents": "[Blood picture in lactate acidosis. Part 2: acid-base equilibrium and lactate]. A differentiation between lactate emia (lactic acid emia) and lactate acidosis (lactic acidosis) is made. The normal value for blood lactate concentration is 1-2 mmol/1. The term lactate emia is used for lactate values between 2-6 mmol/1. The limiting value for the diagnosis of lactate acidosis should be more than 7-8 mmol/1 for the blood lactate concentration. Furthermore the different buffer mechanisms are evaluated in respect to their influence on the pH of the blood and to lactate metabolism. Especially the mechanism of respiratory compensation for metabolic acidosis is discussed. It is stated that for the diagnosis of lactate acidosis the blood-pH and the bicarbonate concentration should be measured."}
{"id": "PMID:18391", "title": "[The disease entity of lactate acidosis. 3. Lactate as a metabolic product].", "content": "High blood lactate concentrations can be achieved by means of intravenous bicarbonate infusion. Metabolic production of lactic acid in this case is a compensation mechanism for the alcalosis induced by bicarbonate. This metabolic condition is called lactate alcalosis. The meaning and the diagnostic value of the lactate/pyruvate quotient and of excess lactate are discussed. A metabolic increase of the lactate/pyruvate quotient (normal values being 10-20) can be attained during the intravenous application of polyalcohols (like xylitol or sorbitol) or of ethanol. In these cases blood lactate concentration remains approximately normal. The alterations are due to the metabolism of the alcohols predominantly in the cytoplasmic compartment of the hepatocytes. The anion-gap is caused by the fact that the anions are considered only in part. However, the diagnostic value of the anion-gap is only minimum. An increase in the anion-gap with a simultaneous decrease in blood-pH is not significant for a lactate acidosis.", "contents": "[The disease entity of lactate acidosis. 3. Lactate as a metabolic product]. High blood lactate concentrations can be achieved by means of intravenous bicarbonate infusion. Metabolic production of lactic acid in this case is a compensation mechanism for the alcalosis induced by bicarbonate. This metabolic condition is called lactate alcalosis. The meaning and the diagnostic value of the lactate/pyruvate quotient and of excess lactate are discussed. A metabolic increase of the lactate/pyruvate quotient (normal values being 10-20) can be attained during the intravenous application of polyalcohols (like xylitol or sorbitol) or of ethanol. In these cases blood lactate concentration remains approximately normal. The alterations are due to the metabolism of the alcohols predominantly in the cytoplasmic compartment of the hepatocytes. The anion-gap is caused by the fact that the anions are considered only in part. However, the diagnostic value of the anion-gap is only minimum. An increase in the anion-gap with a simultaneous decrease in blood-pH is not significant for a lactate acidosis."}
{"id": "PMID:18392", "title": "Disparity between insulin and proinsulin on stimulation of hepatic tyrosine transaminase.", "content": "The ability of insulin and proinsulin to stimulate tyrosine transaminase in dexamethasone-treated cultured rat liver cells was compared. Insulin increased this enzyme whereas proinsulin was seemingly without effect. Since proinsulin was not degraded by these cells, failure of stimulation of hepatic tyrosine transaminase could not be due to rapid destruction of the prohormone. This is the first demonstration of an action of insulin that cannot be duplicated by proinsulin.", "contents": "Disparity between insulin and proinsulin on stimulation of hepatic tyrosine transaminase. The ability of insulin and proinsulin to stimulate tyrosine transaminase in dexamethasone-treated cultured rat liver cells was compared. Insulin increased this enzyme whereas proinsulin was seemingly without effect. Since proinsulin was not degraded by these cells, failure of stimulation of hepatic tyrosine transaminase could not be due to rapid destruction of the prohormone. This is the first demonstration of an action of insulin that cannot be duplicated by proinsulin."}
{"id": "PMID:18393", "title": "Iodotyrosine deiodination in the normal and acutely TSH-stimulated thyroid.", "content": "The deiodination of L-MIT-125I was measured in rat thyroid homogenates and slices before and after acute TSH stimulation. Slices and homogenates were incubated with identical concentrations of tissue and substrate in the presence and absence of NADPH. 1 USP unit TSH added in vitro to thyroid slices failed to stimulate deiodination; a single in vivo ip injection of 3 USP units TSH was also unable to raise deiodinating activity. In contrast to TSH, NADPH added to homogenates and slices enhanced deiodination significantly. However, several arguments, including a review of the literature, strongly militate against the hypothesis of an increased intracellular concentration of the coenzyme NADPH being the prerequisite to enhanced deiodination. The results suggest that deiodinase activity in acutely stimulated thyroids is not limited by the intracellular concentration of the enzyme itself nor by the availability of co-enzyme. Therefore, the increased iodide release induced by acute TSH stimulation is a mere consequence of the enhanced thyroglobulin proteolysis and does not require higher enzyme concentration. It will be shown subsequently that a different conclusion must be drawn in experiments with chronic TSH stimulation.", "contents": "Iodotyrosine deiodination in the normal and acutely TSH-stimulated thyroid. The deiodination of L-MIT-125I was measured in rat thyroid homogenates and slices before and after acute TSH stimulation. Slices and homogenates were incubated with identical concentrations of tissue and substrate in the presence and absence of NADPH. 1 USP unit TSH added in vitro to thyroid slices failed to stimulate deiodination; a single in vivo ip injection of 3 USP units TSH was also unable to raise deiodinating activity. In contrast to TSH, NADPH added to homogenates and slices enhanced deiodination significantly. However, several arguments, including a review of the literature, strongly militate against the hypothesis of an increased intracellular concentration of the coenzyme NADPH being the prerequisite to enhanced deiodination. The results suggest that deiodinase activity in acutely stimulated thyroids is not limited by the intracellular concentration of the enzyme itself nor by the availability of co-enzyme. Therefore, the increased iodide release induced by acute TSH stimulation is a mere consequence of the enhanced thyroglobulin proteolysis and does not require higher enzyme concentration. It will be shown subsequently that a different conclusion must be drawn in experiments with chronic TSH stimulation."}
{"id": "PMID:18395", "title": "Specific, water-soluble polypeptides in identified neurons of Aplysia californica.", "content": "Application of an ethylene glycol lysis technique to extract water-soluble, low molecular weight polypeptides in Aplysia neurons, was used in conjunction with microgradient gel electrophoresis and micro-isoelectric focusing, to identify unique polypeptides in specific, identified neurons. The polypeptides found in neurons R15, R3-13, R14, and the bag cells were particularly abundant, consistent with the previously suggested neurosecretory role for these cells. Water extraction of the strongly basic polypeptides (pI 10.7) in R3-13 and R14 required an acidic lysis medium.", "contents": "Specific, water-soluble polypeptides in identified neurons of Aplysia californica. Application of an ethylene glycol lysis technique to extract water-soluble, low molecular weight polypeptides in Aplysia neurons, was used in conjunction with microgradient gel electrophoresis and micro-isoelectric focusing, to identify unique polypeptides in specific, identified neurons. The polypeptides found in neurons R15, R3-13, R14, and the bag cells were particularly abundant, consistent with the previously suggested neurosecretory role for these cells. Water extraction of the strongly basic polypeptides (pI 10.7) in R3-13 and R14 required an acidic lysis medium."}
{"id": "PMID:18396", "title": "Distribution of beta-N-acetylglucosaminidase, hyaluronoglucosaminidase and acrosin in buffalo and goat spermatozoa.", "content": "The distribution of beta-N-acetylglucosaminidase, hyaluronoglucosaminidase and acrosin in buffalo and goat sperm acrosomes was studied. The three hydrolases were found to occur in soluble and bound forms. In the bound form, they were associated with the denuded sperm and were maximally solubilized at pH 3.0. The possible role of beta-N-acetylglucosaminidase in fertilization is discussed.", "contents": "Distribution of beta-N-acetylglucosaminidase, hyaluronoglucosaminidase and acrosin in buffalo and goat spermatozoa. The distribution of beta-N-acetylglucosaminidase, hyaluronoglucosaminidase and acrosin in buffalo and goat sperm acrosomes was studied. The three hydrolases were found to occur in soluble and bound forms. In the bound form, they were associated with the denuded sperm and were maximally solubilized at pH 3.0. The possible role of beta-N-acetylglucosaminidase in fertilization is discussed."}
{"id": "PMID:18397", "title": "[Purification and properties of the tetrahydropteroylglutamate methyltransferase from green beans (Phaseolus vulgaris) (author's transl)].", "content": "The tetrahydropteroylglutamate methyltransferase from green beans (Phaseolus vulgaris) has been purified 80-fold by ion exchange chromatography and gel filtration. Optimal methyl transfer is found at pH 6.5 and 39 degrees C. Even at 0 degrees C, however, a considerable catalytic rate is observed. The Michaelis-Menten constants for homocysteine and 5-methyltetrahydropteroylglutamate are 0.43mM and 2.4 mM, respectively. Magnesium ions enhance the activity. Even purified preparations appear to contain traces of magnesium ions firmly bound, since a residual activity is found without addition of magnesium salts. Though the reaction requires anaerobiosis, an excess of reducing agents is inhibitory. The molecular weight of the transferase, determined by gel filtration, is 40 000 +/- 6%.", "contents": "[Purification and properties of the tetrahydropteroylglutamate methyltransferase from green beans (Phaseolus vulgaris) (author's transl)]. The tetrahydropteroylglutamate methyltransferase from green beans (Phaseolus vulgaris) has been purified 80-fold by ion exchange chromatography and gel filtration. Optimal methyl transfer is found at pH 6.5 and 39 degrees C. Even at 0 degrees C, however, a considerable catalytic rate is observed. The Michaelis-Menten constants for homocysteine and 5-methyltetrahydropteroylglutamate are 0.43mM and 2.4 mM, respectively. Magnesium ions enhance the activity. Even purified preparations appear to contain traces of magnesium ions firmly bound, since a residual activity is found without addition of magnesium salts. Though the reaction requires anaerobiosis, an excess of reducing agents is inhibitory. The molecular weight of the transferase, determined by gel filtration, is 40 000 +/- 6%."}
{"id": "PMID:18400", "title": "Induction of placental alkaline phosphatase in choriocarcinoma cells by 5-bromo-2'-deoxyuridine.", "content": "Growth of choriocarcinoma cells in the presence of 5-bromo-2'-deoxyuridine (BrdUrd) results in a 30- to 40-fold increase in alkaline phosphatase activity. The effects of BrdUrd is specific for phosphatase with an alkaline pH optimum. The induction by BrdUrd is probably not due to the production of an altered enzyme, since the induced enzyme resembles the basal enzyme in thermal denaturation and kinetic properties. Enzyme induction can be prevented by thymidine but not by deoxycytidine or deoxyuridine. The induction of alkaline phosphatase appears to require incorporation of the BrdUrd into cellular DNA. The presence of BrdUrd in the growth medium is not necessary for alkaline phosphatase induction in proliferating cells containing BrdUrd-substituted genomes. However, enzyme induction and maintenance of the induced levels of alkaline phosphatase in nonproliferating cells containing BrdUrd-substituted DNA requires the presence of the analogues in the medium. The induction of alkaline phosphatase by BrdUrd in probably an indirect process.", "contents": "Induction of placental alkaline phosphatase in choriocarcinoma cells by 5-bromo-2'-deoxyuridine. Growth of choriocarcinoma cells in the presence of 5-bromo-2'-deoxyuridine (BrdUrd) results in a 30- to 40-fold increase in alkaline phosphatase activity. The effects of BrdUrd is specific for phosphatase with an alkaline pH optimum. The induction by BrdUrd is probably not due to the production of an altered enzyme, since the induced enzyme resembles the basal enzyme in thermal denaturation and kinetic properties. Enzyme induction can be prevented by thymidine but not by deoxycytidine or deoxyuridine. The induction of alkaline phosphatase appears to require incorporation of the BrdUrd into cellular DNA. The presence of BrdUrd in the growth medium is not necessary for alkaline phosphatase induction in proliferating cells containing BrdUrd-substituted genomes. However, enzyme induction and maintenance of the induced levels of alkaline phosphatase in nonproliferating cells containing BrdUrd-substituted DNA requires the presence of the analogues in the medium. The induction of alkaline phosphatase by BrdUrd in probably an indirect process."}
{"id": "PMID:18403", "title": "Effects of trypan blue treatment on the immune responses of mice.", "content": "It has been reported that trypan blue treatment decreases the nonspecific resistance of mice to transplanted tumors and inhibits the in vitro cytotoxic activity of activated macrophages. We wished to determine whether this effect of trypan blue could be due to a selective inhibition of certain macrophage functions or whether it reflected a broader form of immunosuppression. We therefore tested the effects of trypan blue on a variety of immunological responses. Treatment of mice with trypan blue delayed their rejection of skin allografts and transplants of a highly antigenic syngeneic ultraviolet light-induced tumor. Trypan blue treatment of either donor or recipient decreased the local graft-versus-host reaction. Filtration of lymph node cells from trypan blue-treated donors on a nylon wool column before use in the graft-versus-host assay abrogated the depressive effect of trypan blue. A transient reduction in the blastogenic response of spleen cells to concanavalin A and lipopolysaccharide mitogens was observed after a single injection of trypan blue, but the response of lymph node cells was unaffected. The depressed response of splenic lymphocytes was not entirely reversed by removal of adherent cells. The primary and secondary hemagglutinin responses to sheep erythrocytes were unaffected in trypan blue-treated mice, and the proportion and phagocytic activity of thioglycolate-induced peritoneal macrophages were also unaltered. We conclude that treatment of mice with trypan blue selectively inhibits certain macrophage functions but, at high doses, it can also inhibit some lymphocyte activities.", "contents": "Effects of trypan blue treatment on the immune responses of mice. It has been reported that trypan blue treatment decreases the nonspecific resistance of mice to transplanted tumors and inhibits the in vitro cytotoxic activity of activated macrophages. We wished to determine whether this effect of trypan blue could be due to a selective inhibition of certain macrophage functions or whether it reflected a broader form of immunosuppression. We therefore tested the effects of trypan blue on a variety of immunological responses. Treatment of mice with trypan blue delayed their rejection of skin allografts and transplants of a highly antigenic syngeneic ultraviolet light-induced tumor. Trypan blue treatment of either donor or recipient decreased the local graft-versus-host reaction. Filtration of lymph node cells from trypan blue-treated donors on a nylon wool column before use in the graft-versus-host assay abrogated the depressive effect of trypan blue. A transient reduction in the blastogenic response of spleen cells to concanavalin A and lipopolysaccharide mitogens was observed after a single injection of trypan blue, but the response of lymph node cells was unaffected. The depressed response of splenic lymphocytes was not entirely reversed by removal of adherent cells. The primary and secondary hemagglutinin responses to sheep erythrocytes were unaffected in trypan blue-treated mice, and the proportion and phagocytic activity of thioglycolate-induced peritoneal macrophages were also unaltered. We conclude that treatment of mice with trypan blue selectively inhibits certain macrophage functions but, at high doses, it can also inhibit some lymphocyte activities."}
{"id": "PMID:18404", "title": "Lung bacterial clearance in murine pneumococcal pneumonia.", "content": "We studied the bactericidal capacity of the rat lung during the development of pneumococcal pneumonia. Pneumonia was produced in a lower lobe by the intrabronchial instillation of 10(4)Streptococcus pneumoniae cells in buffer. Lung bacterial counts progressively increased, reaching 10(7) per lung within 48 h, and the increase was associated with localized atelectasis and consolidation. Bacterial multiplication was inhibited with tetracycline at various intervals after infection, and the subsequent clearance of pneumococci was determined. Viable pneumococci were rapidly killed by lung defenses if bacterial multiplication was inhibited within 12 h of the onset of infection. No change occurred in the bacterial populationif tetracycline was delayed until 24 h after infection, indicating that pneumococcal killing by lung defenses had ceased. This effect could be reproduced with the addition of pneumococcal capsular polysaccharide to the inoculum, which produced a dose-related inhibition of pneumococcal clearance. The clearance of S. epidermidis was not impaired in the presence of pneumococcal pneumonia or by administration of exogenous capsular polysaccharide. These data indicate that pneumococcal pneumonia causes a marked impairment in lung antipneumococcal defenses within 24 h of the onset of infection. This acquired defect in antibacterial defenses may be due to the accumulation of pneumococcal capsular material in the lungs of infected animals.", "contents": "Lung bacterial clearance in murine pneumococcal pneumonia. We studied the bactericidal capacity of the rat lung during the development of pneumococcal pneumonia. Pneumonia was produced in a lower lobe by the intrabronchial instillation of 10(4)Streptococcus pneumoniae cells in buffer. Lung bacterial counts progressively increased, reaching 10(7) per lung within 48 h, and the increase was associated with localized atelectasis and consolidation. Bacterial multiplication was inhibited with tetracycline at various intervals after infection, and the subsequent clearance of pneumococci was determined. Viable pneumococci were rapidly killed by lung defenses if bacterial multiplication was inhibited within 12 h of the onset of infection. No change occurred in the bacterial populationif tetracycline was delayed until 24 h after infection, indicating that pneumococcal killing by lung defenses had ceased. This effect could be reproduced with the addition of pneumococcal capsular polysaccharide to the inoculum, which produced a dose-related inhibition of pneumococcal clearance. The clearance of S. epidermidis was not impaired in the presence of pneumococcal pneumonia or by administration of exogenous capsular polysaccharide. These data indicate that pneumococcal pneumonia causes a marked impairment in lung antipneumococcal defenses within 24 h of the onset of infection. This acquired defect in antibacterial defenses may be due to the accumulation of pneumococcal capsular material in the lungs of infected animals."}
{"id": "PMID:18405", "title": "Mild alkaline hydrolysis of lipopolysaccharide endotoxin enhances its mitogencity for murine B cells.", "content": "Mild alkaline hydrolysis was found to enhance the mitogenicity of lipopolysaccharide endotoxin for murine B lymphocytes. Alkaline treated lipopolysaccharide also retained its property as a polyclonal activator. Whereas this treatment reduced the lethality of endotoxin for mice, its toxicity for lymphocytes cultured in the absence of fetal calf serum was increased. Lipid analysis indicated that there were no significant changes in the fatty acids of lipid A, but particle size was significantly reduced and the material was more homogeneous and soluble than untreated lipopolysaccharide. The relationship of these effect on the structure of lipopolysaccharide endotoxin to the mechanism of B-lymphocyte activation is discussed.", "contents": "Mild alkaline hydrolysis of lipopolysaccharide endotoxin enhances its mitogencity for murine B cells. Mild alkaline hydrolysis was found to enhance the mitogenicity of lipopolysaccharide endotoxin for murine B lymphocytes. Alkaline treated lipopolysaccharide also retained its property as a polyclonal activator. Whereas this treatment reduced the lethality of endotoxin for mice, its toxicity for lymphocytes cultured in the absence of fetal calf serum was increased. Lipid analysis indicated that there were no significant changes in the fatty acids of lipid A, but particle size was significantly reduced and the material was more homogeneous and soluble than untreated lipopolysaccharide. The relationship of these effect on the structure of lipopolysaccharide endotoxin to the mechanism of B-lymphocyte activation is discussed."}
{"id": "PMID:18402", "title": "Effect of some antihistaminic drugs on the oestrous cycyle of rats.", "content": "The effect of some antihistaminic drugs namely antazoline hydrochloride, diphenhy, dramine hydrochloride and mepyramine maleate has been investigated on the oestrous cycle in albino rats. On daily intraperitoneal administration, for 6 days, all the three drugs (10 mg/kg) significantly (P less than 0.001) prolonged the duration of oestrous cycle. The duration of subsequent cycle returned to near normal.", "contents": "Effect of some antihistaminic drugs on the oestrous cycyle of rats. The effect of some antihistaminic drugs namely antazoline hydrochloride, diphenhy, dramine hydrochloride and mepyramine maleate has been investigated on the oestrous cycle in albino rats. On daily intraperitoneal administration, for 6 days, all the three drugs (10 mg/kg) significantly (P less than 0.001) prolonged the duration of oestrous cycle. The duration of subsequent cycle returned to near normal."}
{"id": "PMID:18406", "title": "[Assay of aminoglycosides in serum using the urease method (author's transl)].", "content": "The urease method developed by Noone et al. for rapid bioassay of aminoglycoside antibiotics in serum is described in detail. The accuracy of the method was improved by using a BM 1-09 electrode assembly (Metrohm, CH-9100 Herisau, Switzerland) in conjunction with a digital pH-Meter (Metrohm E 500). The mean difference between spiked serum samples and measured concentrations was +0.37 +/-0.78 microgram/ml. The coefficient of determination between the urease and agar diffusion method was 0.94. Disadvantages of the method are a low sensitivity at concentrations below 1.5 microgram/ml and a large serum sample (1.5 ml). Advantages are its simplicity and rapidity.", "contents": "[Assay of aminoglycosides in serum using the urease method (author's transl)]. The urease method developed by Noone et al. for rapid bioassay of aminoglycoside antibiotics in serum is described in detail. The accuracy of the method was improved by using a BM 1-09 electrode assembly (Metrohm, CH-9100 Herisau, Switzerland) in conjunction with a digital pH-Meter (Metrohm E 500). The mean difference between spiked serum samples and measured concentrations was +0.37 +/-0.78 microgram/ml. The coefficient of determination between the urease and agar diffusion method was 0.94. Disadvantages of the method are a low sensitivity at concentrations below 1.5 microgram/ml and a large serum sample (1.5 ml). Advantages are its simplicity and rapidity."}
{"id": "PMID:18407", "title": "Circulating prolactin levels. I. Normal females.", "content": "A specific, homologous radioimmunoassay was used to quantitate circulating levels of prolactin in females in various stages of life. They were grouped in periods of newborns to peripubertal females, reproductive, gravid and puerperal, and postmenopausal females. The results reveal dynamic changes of prolactin throughout various stages of life and support the mounting evidence that prolactin's role in humans might mimic that of animals. The role of prolactin in the ovarian cycle is unclear and will have to be ascertained at the molecular level.", "contents": "Circulating prolactin levels. I. Normal females. A specific, homologous radioimmunoassay was used to quantitate circulating levels of prolactin in females in various stages of life. They were grouped in periods of newborns to peripubertal females, reproductive, gravid and puerperal, and postmenopausal females. The results reveal dynamic changes of prolactin throughout various stages of life and support the mounting evidence that prolactin's role in humans might mimic that of animals. The role of prolactin in the ovarian cycle is unclear and will have to be ascertained at the molecular level."}
{"id": "PMID:18408", "title": "Follicular development during late human pregnancy.", "content": "In contrast to the accepted view of ovarian quiescence during pregnancy, the ovaries of preparturient women are covered with a dense population of small superficial follicles. In this study we have measured the follicular size and status of the oocytes and cumulus oophorus in 298 follicles from the ovaries of 30 women. The samples were taken at cesarean section and were examined with Nomarski differential interference microscopy. No oocyte was recovered from 50% of the follicles; 79% of the recovered oocytes and 78% of their cumuli were degenerative. Degeneration was correlated with appearance of phagocytes in the follicular fluid. These findings suggest that the endocrine status of gestation does not prevent early follicular development, but induces premature atresia.", "contents": "Follicular development during late human pregnancy. In contrast to the accepted view of ovarian quiescence during pregnancy, the ovaries of preparturient women are covered with a dense population of small superficial follicles. In this study we have measured the follicular size and status of the oocytes and cumulus oophorus in 298 follicles from the ovaries of 30 women. The samples were taken at cesarean section and were examined with Nomarski differential interference microscopy. No oocyte was recovered from 50% of the follicles; 79% of the recovered oocytes and 78% of their cumuli were degenerative. Degeneration was correlated with appearance of phagocytes in the follicular fluid. These findings suggest that the endocrine status of gestation does not prevent early follicular development, but induces premature atresia."}
{"id": "PMID:18409", "title": "Successful separation of X and Y and spermatozoa in human and bull semen.", "content": "Using particle free semen extender and applying a low temperature thermal convection laminar flow to bring the sperm cells in vertical orientation and allowing them to act through the center of buoyancy, a bimodal distribution was achieved. Laser scanner for observing sedimentation pattern and F-body technique for identification of male sperm were used. Specimens from five human donors and ten bulls were separated, checked for purity, and frozen in liquid nitrogen. The lighter fractions contained 59.4% male (P less than 0.01), the heavier fractions 63.5% female (P less than 0.01), and the nonprocessed semen 48.0% male cells. Over 10,000 cells were counted to arrive at this statistically significant result. Observed sex ratio closely matched the predicted purity figures. Lighter and heavier fractions were further purified using forced convection galvanic method. Seventy to eighty percent purity in both fractions was confirmed by F-body and small cell galvanic migration tests with human as well as with bull semen.", "contents": "Successful separation of X and Y and spermatozoa in human and bull semen. Using particle free semen extender and applying a low temperature thermal convection laminar flow to bring the sperm cells in vertical orientation and allowing them to act through the center of buoyancy, a bimodal distribution was achieved. Laser scanner for observing sedimentation pattern and F-body technique for identification of male sperm were used. Specimens from five human donors and ten bulls were separated, checked for purity, and frozen in liquid nitrogen. The lighter fractions contained 59.4% male (P less than 0.01), the heavier fractions 63.5% female (P less than 0.01), and the nonprocessed semen 48.0% male cells. Over 10,000 cells were counted to arrive at this statistically significant result. Observed sex ratio closely matched the predicted purity figures. Lighter and heavier fractions were further purified using forced convection galvanic method. Seventy to eighty percent purity in both fractions was confirmed by F-body and small cell galvanic migration tests with human as well as with bull semen."}
{"id": "PMID:18410", "title": "Autoradiographic studies of rabbit ova after fertilization with thymidine-H3 and -C14 labelled spermatozoa originating from different bucks.", "content": "Rabbit spermatozoa were labelled in vivo injecting male rabbits with thymidine-H3 and thymidine-C14. Ova fertilized with H3-labelled spermatozoa were found to contain more silver grains when they had cleaved several times than before cleavage. Fertilized ova originating from rabbits that had been mated with both an H3- and C14-thymidine labelled buck carried both labels. An explanation for this phenomenon may be that additional spermatozoa in the perivitelline space of fertilized ova pass labelled DNA-bases to the cleaving blastomeres.", "contents": "Autoradiographic studies of rabbit ova after fertilization with thymidine-H3 and -C14 labelled spermatozoa originating from different bucks. Rabbit spermatozoa were labelled in vivo injecting male rabbits with thymidine-H3 and thymidine-C14. Ova fertilized with H3-labelled spermatozoa were found to contain more silver grains when they had cleaved several times than before cleavage. Fertilized ova originating from rabbits that had been mated with both an H3- and C14-thymidine labelled buck carried both labels. An explanation for this phenomenon may be that additional spermatozoa in the perivitelline space of fertilized ova pass labelled DNA-bases to the cleaving blastomeres."}
{"id": "PMID:18411", "title": "Absence of a prenidatory effect of luteinizing hormone releasing hormone (LHRH) in hamsters.", "content": "Luteinizing hormone releasing hormone at high doses will terminate gestation in rats during early and midpregancy (ED50 approximately equal to 100 microgram/day) and rabbits during early pregnancy. Early pregnancy in hamsters, in contradistinction, seems refractory to this effect. Administration of LHRH up to massive doses (10 mg/day) over the first 3 or 7 days of pregnancy failed to affect the pregnancies in meaningful fashion. Further, a single injection (100 mg) on day 5 had no effect on pregnancy; this system has been employed for the assay of prostaglandins because hamsters are remarkably sensitive to PG's (PGF2alpha, ED50 approximately equal to 17 microgram, PGE2, ED50 approximately equal to 210 microgram). The absence of response of hamsters to LHRH cannot be interpreted at present.", "contents": "Absence of a prenidatory effect of luteinizing hormone releasing hormone (LHRH) in hamsters. Luteinizing hormone releasing hormone at high doses will terminate gestation in rats during early and midpregancy (ED50 approximately equal to 100 microgram/day) and rabbits during early pregnancy. Early pregnancy in hamsters, in contradistinction, seems refractory to this effect. Administration of LHRH up to massive doses (10 mg/day) over the first 3 or 7 days of pregnancy failed to affect the pregnancies in meaningful fashion. Further, a single injection (100 mg) on day 5 had no effect on pregnancy; this system has been employed for the assay of prostaglandins because hamsters are remarkably sensitive to PG's (PGF2alpha, ED50 approximately equal to 17 microgram, PGE2, ED50 approximately equal to 210 microgram). The absence of response of hamsters to LHRH cannot be interpreted at present."}
{"id": "PMID:18412", "title": "The role of prostaglandins on the increase in motility of the rat-uterine horn containing a silk suture.", "content": "The presence of a silk suture in one uterine horn of the rats leads to an increase in spontaneous motility when compared with the contralateral control horn. Indomethacin, an inhibitor of prostaglandin synthetase inhibits the motility suggesting a role of prostaglandins in this process.", "contents": "The role of prostaglandins on the increase in motility of the rat-uterine horn containing a silk suture. The presence of a silk suture in one uterine horn of the rats leads to an increase in spontaneous motility when compared with the contralateral control horn. Indomethacin, an inhibitor of prostaglandin synthetase inhibits the motility suggesting a role of prostaglandins in this process."}
{"id": "PMID:18413", "title": "Paper chromatographic estimation of fructose and myo-inositol in human seminal fluid: a method for evaluating seminal vesicle and prostatic function.", "content": "A semiquantitative paper chromatographic method for the separation of myo-inositol and fructose in human seminal fluid was described. The intensity of the chromatographic zones characteristic of myo-inositol, which is a marker for human prostatic secretion and for fructose, which is useful in evaluating seminal vesicle function, were estimated after staining with an alkaline silver nitrate reagent. Characteristic patterns were found for patients with prostatic or vesicular dysfunction, and for patients with agenesis or blockage of the vas deferens. Paper chromatographic analysis of split ejaculate samples allowed evaluation of the sequence of ejaculation of the prostate and seminal vesicles.", "contents": "Paper chromatographic estimation of fructose and myo-inositol in human seminal fluid: a method for evaluating seminal vesicle and prostatic function. A semiquantitative paper chromatographic method for the separation of myo-inositol and fructose in human seminal fluid was described. The intensity of the chromatographic zones characteristic of myo-inositol, which is a marker for human prostatic secretion and for fructose, which is useful in evaluating seminal vesicle function, were estimated after staining with an alkaline silver nitrate reagent. Characteristic patterns were found for patients with prostatic or vesicular dysfunction, and for patients with agenesis or blockage of the vas deferens. Paper chromatographic analysis of split ejaculate samples allowed evaluation of the sequence of ejaculation of the prostate and seminal vesicles."}
{"id": "PMID:18414", "title": "Gonadal function following vasectomy in the rat.", "content": "Adult rats were studied at four, eight, and 12 months following vasectomy and sham-operation. The weights of the seminal vesicles, ventral prostate, pituitary, and kidneys were not significantly affected by vasectomy. Testicular endocrine function in vasectotomized rat was transiently stimulated as witnessed by elevation in testicular venous testosterone and androstenedione after four months. There then occurred signs of decline in gametogenic function and atrophy of the testis after 12 months whereas hormonogenesis appeared to remain at normal levels. There was no alteration in the morphology of the epididymis at any of the time intervals of study after vasectomy.", "contents": "Gonadal function following vasectomy in the rat. Adult rats were studied at four, eight, and 12 months following vasectomy and sham-operation. The weights of the seminal vesicles, ventral prostate, pituitary, and kidneys were not significantly affected by vasectomy. Testicular endocrine function in vasectotomized rat was transiently stimulated as witnessed by elevation in testicular venous testosterone and androstenedione after four months. There then occurred signs of decline in gametogenic function and atrophy of the testis after 12 months whereas hormonogenesis appeared to remain at normal levels. There was no alteration in the morphology of the epididymis at any of the time intervals of study after vasectomy."}
{"id": "PMID:18415", "title": "Testosterone production and metabolism in laboratory-maintained male rhesus monkeys.", "content": "Plasma production rates (PR), metabolic clearance rates (MCR) and plasma levels of testosterone were determined in 10 male, laboratory-maintained rhesus monkeys on two occasions out-of-season (April and August) and once in-season (October). Plasma testosterone levels in October were higher than those in April and August. The plasma PR was unchanged in August, but markedly increased in October, as compared to April. The MCR showed a parallel increase betueen August and October. Thus changes in testosterone production and metabolism can be observed between in- and out-of-season male rhesus monkeys, maintained under strict laboratory conditions. These changes must be taken into consideration when the male rhesus minkey is used as an experimental model for human reproductive endocrinology.", "contents": "Testosterone production and metabolism in laboratory-maintained male rhesus monkeys. Plasma production rates (PR), metabolic clearance rates (MCR) and plasma levels of testosterone were determined in 10 male, laboratory-maintained rhesus monkeys on two occasions out-of-season (April and August) and once in-season (October). Plasma testosterone levels in October were higher than those in April and August. The plasma PR was unchanged in August, but markedly increased in October, as compared to April. The MCR showed a parallel increase betueen August and October. Thus changes in testosterone production and metabolism can be observed between in- and out-of-season male rhesus monkeys, maintained under strict laboratory conditions. These changes must be taken into consideration when the male rhesus minkey is used as an experimental model for human reproductive endocrinology."}
{"id": "PMID:18416", "title": "Pituitary and ovarian response to acute stimulation with LH-RH in normal and anovulatory women.", "content": "The LH FSH estradiol and progesterone responses to acute stimulation with LH-RH were studied in 12 normal women with ovulatory cycles (4 in the initial follicular phase, 4 in the mid-follicular phase and 4 in the late follicular phase) and in two castrated women, two under hormonal contraception, two with ovarian amenorrhea, twelve with central amenorrhea of no detectable origin (6 with normal and 6 with low basal gonadotrophins), eleven anovulatory patients with pseudomenstruation, two with anorexia nervosa, and two with pituitary amenorrhea. Each woman received a rapid i.v. injection of 100 microgram synthetic LH-RH at 9:00 a.m. Serum levels of LH, FSH, estradiol and progesterone were determined by radioimmunoassay in samples collected before and 60, 120, 240 and 480 minutes after injection. The findings were : 1) A significant rise in estradiol and progesterone levels, in addition to LH and FSH elevation, in normal women; 2) A lack of ovarian steroid response in the castrated women and in ovarian amenorrheas, which suggests that the source of steroid response to stimulation is not extragonadal; 3) Significant differences in the responses of the four hormones to LH-RH in the women with central amenorrhea in comparison with the normal group with great variability of results; the steroid response in the presence of a positive LH response might correlate with the severity and/or prognosis of the disorder, a point deserving further study; 4) In anovulatory women with pseudomenstruation, LH responses for the most part normal, and particularly, progesterone responses.", "contents": "Pituitary and ovarian response to acute stimulation with LH-RH in normal and anovulatory women. The LH FSH estradiol and progesterone responses to acute stimulation with LH-RH were studied in 12 normal women with ovulatory cycles (4 in the initial follicular phase, 4 in the mid-follicular phase and 4 in the late follicular phase) and in two castrated women, two under hormonal contraception, two with ovarian amenorrhea, twelve with central amenorrhea of no detectable origin (6 with normal and 6 with low basal gonadotrophins), eleven anovulatory patients with pseudomenstruation, two with anorexia nervosa, and two with pituitary amenorrhea. Each woman received a rapid i.v. injection of 100 microgram synthetic LH-RH at 9:00 a.m. Serum levels of LH, FSH, estradiol and progesterone were determined by radioimmunoassay in samples collected before and 60, 120, 240 and 480 minutes after injection. The findings were : 1) A significant rise in estradiol and progesterone levels, in addition to LH and FSH elevation, in normal women; 2) A lack of ovarian steroid response in the castrated women and in ovarian amenorrheas, which suggests that the source of steroid response to stimulation is not extragonadal; 3) Significant differences in the responses of the four hormones to LH-RH in the women with central amenorrhea in comparison with the normal group with great variability of results; the steroid response in the presence of a positive LH response might correlate with the severity and/or prognosis of the disorder, a point deserving further study; 4) In anovulatory women with pseudomenstruation, LH responses for the most part normal, and particularly, progesterone responses."}
{"id": "PMID:18417", "title": "Seminal fructose and acid phosphatase in vasectomised men.", "content": "Seminal fructose and acid phosphatase levels have been determined in 30 vasectomised and 30 nonvasectomised healthy adults, both the groups being closely matched for age (32 to 45 years). The fructose and acid phosphatase values in the vasectomised men, 3 to 6 months after the operation, were 316 +/- 36 mg% and 2,098 +/- 112 K.A. units/ml, respectively, while in the control group they were 251 +/- 28 mg% and 1,932 +/- 92 K.A. units/ml. The differences are statistically significant (P less than 0.001) and the possible implications of the post-vasectomy rise in these androgen dependent seminal constituents are discussed.", "contents": "Seminal fructose and acid phosphatase in vasectomised men. Seminal fructose and acid phosphatase levels have been determined in 30 vasectomised and 30 nonvasectomised healthy adults, both the groups being closely matched for age (32 to 45 years). The fructose and acid phosphatase values in the vasectomised men, 3 to 6 months after the operation, were 316 +/- 36 mg% and 2,098 +/- 112 K.A. units/ml, respectively, while in the control group they were 251 +/- 28 mg% and 1,932 +/- 92 K.A. units/ml. The differences are statistically significant (P less than 0.001) and the possible implications of the post-vasectomy rise in these androgen dependent seminal constituents are discussed."}
{"id": "PMID:18418", "title": "The 'in vivo' effects of oxytocin and vasopressin on spontaneous contractility of the rat epididymis.", "content": "The spontaneous contractility of the epididymis in the rat was recorded in vivo and the effects of the neurohypophyseal hormones were studied. Oxytocin (50 muU and 500 muU/100 g body weight) produced a progressive increase in tonus together with an increase in amplitude and frequency of the contractions. Vasopressin (100 muU and 1000 muU/100 g body weight) showed similar effects. No differences were apparent at the doses studied.", "contents": "The 'in vivo' effects of oxytocin and vasopressin on spontaneous contractility of the rat epididymis. The spontaneous contractility of the epididymis in the rat was recorded in vivo and the effects of the neurohypophyseal hormones were studied. Oxytocin (50 muU and 500 muU/100 g body weight) produced a progressive increase in tonus together with an increase in amplitude and frequency of the contractions. Vasopressin (100 muU and 1000 muU/100 g body weight) showed similar effects. No differences were apparent at the doses studied."}
{"id": "PMID:18420", "title": "Interpretation of thermal perturbation spectra of proteins.", "content": "The thermal perturbation difference spectrum of reduced lysozyme has a long wave length extremum at 304 nm at pH 6.15 and a very small extremum at 306 nm at pH 1.5. These results differ from those of Leach & Smith (1972), which showed an extremum at 293 nm, the same as for model tryptophyl compounds. Our result may arise from a conformational difference between the two sample temperatures. The interpretation of thermal perturbation spectra of proteins is discussed. Contributions from thermally induced concentration differences, buried chromophores, and chromophores in  crevices are considered in the interpretation of the thermal perturbation spectrum of bovine serum albumin. It is suggested that chromophores in pauci-aqueous crevices may appear buried toward thermal perturbation spectroscopy but accessible toward solvent perturbation and chemical reagents.", "contents": "Interpretation of thermal perturbation spectra of proteins. The thermal perturbation difference spectrum of reduced lysozyme has a long wave length extremum at 304 nm at pH 6.15 and a very small extremum at 306 nm at pH 1.5. These results differ from those of Leach & Smith (1972), which showed an extremum at 293 nm, the same as for model tryptophyl compounds. Our result may arise from a conformational difference between the two sample temperatures. The interpretation of thermal perturbation spectra of proteins is discussed. Contributions from thermally induced concentration differences, buried chromophores, and chromophores in  crevices are considered in the interpretation of the thermal perturbation spectrum of bovine serum albumin. It is suggested that chromophores in pauci-aqueous crevices may appear buried toward thermal perturbation spectroscopy but accessible toward solvent perturbation and chemical reagents."}
{"id": "PMID:18421", "title": "Stabilisation of enzyme structures by inhibitors. A nuclear magnetic resonance study of the effect of phosphate on the acid unfolding of ribonuclease A.", "content": "The acid denaturation of bovine pancreatic ribonuclease A in the presence of 0.2M sodium dihydrogen phosphate has been studied by n.m.r. spectroscopy. Phenylalanine, tyrosine and methionine resonances serve as monitors of the unfolding process. It is shown that the inhibitor shifts the equilibrium towards the native structure at acid pH. Exchange broadening of the C-2 resonances of the active site histidines, 12 and 119, occurs in the presence of phosphate, suggesting an equilibrium between native and unfolded structures. Stabilisation of the partially unfolded protein is observed at pH 1.5, as evidenced by the lack of the histidine resonance due to random coil protein. A scheme of the equilibria relating the various states of the protein is proposed.", "contents": "Stabilisation of enzyme structures by inhibitors. A nuclear magnetic resonance study of the effect of phosphate on the acid unfolding of ribonuclease A. The acid denaturation of bovine pancreatic ribonuclease A in the presence of 0.2M sodium dihydrogen phosphate has been studied by n.m.r. spectroscopy. Phenylalanine, tyrosine and methionine resonances serve as monitors of the unfolding process. It is shown that the inhibitor shifts the equilibrium towards the native structure at acid pH. Exchange broadening of the C-2 resonances of the active site histidines, 12 and 119, occurs in the presence of phosphate, suggesting an equilibrium between native and unfolded structures. Stabilisation of the partially unfolded protein is observed at pH 1.5, as evidenced by the lack of the histidine resonance due to random coil protein. A scheme of the equilibria relating the various states of the protein is proposed."}
{"id": "PMID:18422", "title": "Levels of neurotransmitters in brain of vitamin B12 deficient rats.", "content": "The levels of norepinephrine, dopamine and 5-hydroxytryptamine in brain homogenates of vitamin B12-deficient rats have been investigated. The norepinephrine levels were significantly decreased in the deficient animals compared to controls. The two major catabolic pathways of norepinephrine e.g. monoamine oxidase and catechol-O-methyl transferase did not show significant variations. Both acetyl cholinesterase and butiryl-cholinesterase markedly decreased in the plasma of the vitamin B12-deficient rats.", "contents": "Levels of neurotransmitters in brain of vitamin B12 deficient rats. The levels of norepinephrine, dopamine and 5-hydroxytryptamine in brain homogenates of vitamin B12-deficient rats have been investigated. The norepinephrine levels were significantly decreased in the deficient animals compared to controls. The two major catabolic pathways of norepinephrine e.g. monoamine oxidase and catechol-O-methyl transferase did not show significant variations. Both acetyl cholinesterase and butiryl-cholinesterase markedly decreased in the plasma of the vitamin B12-deficient rats."}
{"id": "PMID:18423", "title": "The buccal absorption of ascorbic acid and its passage through lipoid membrane.", "content": "Ascorbic acid concentration was measured in centrifuged and uncentrifuged saliva from normal young adult men and women. The salivary ascorbic acid content of uncentrifuged saliva was significantly higher in women on account of the ascorbic acid contained in the cellular sediment. Ascorbic acid absorption into the buccal mucosa was measured from solutions of pH range 3.4-9.0 held in the mouth for periods of 1-9 minutes. For a constant mouth contact time, increase in pH of the loading solutions resulted in reduction of buccal absorption, and diminishing transfer into the buccal epithelium. Percentage absorption was greater in males than females throughout the pH range. At pH 5, 80% of the loading solution was absorbed after 5 minutes. Diffusion of ascorbic acid through the lipoid membrane was more rapid in males. Female buccal cells had significantly higher ascorbic acid concentrations than male cells. Absorption of laevo and dextro ascorbic acid in human beings can be considered as partitioning into, or passage through, a lipoid phase into the buccal cells. The rate of passage of ascorbic acid into the buccal lining cells under controlled conditions of pH and buccal contact time is pH and concentration dependent in human beings.", "contents": "The buccal absorption of ascorbic acid and its passage through lipoid membrane. Ascorbic acid concentration was measured in centrifuged and uncentrifuged saliva from normal young adult men and women. The salivary ascorbic acid content of uncentrifuged saliva was significantly higher in women on account of the ascorbic acid contained in the cellular sediment. Ascorbic acid absorption into the buccal mucosa was measured from solutions of pH range 3.4-9.0 held in the mouth for periods of 1-9 minutes. For a constant mouth contact time, increase in pH of the loading solutions resulted in reduction of buccal absorption, and diminishing transfer into the buccal epithelium. Percentage absorption was greater in males than females throughout the pH range. At pH 5, 80% of the loading solution was absorbed after 5 minutes. Diffusion of ascorbic acid through the lipoid membrane was more rapid in males. Female buccal cells had significantly higher ascorbic acid concentrations than male cells. Absorption of laevo and dextro ascorbic acid in human beings can be considered as partitioning into, or passage through, a lipoid phase into the buccal cells. The rate of passage of ascorbic acid into the buccal lining cells under controlled conditions of pH and buccal contact time is pH and concentration dependent in human beings."}
{"id": "PMID:18425", "title": "Physicochemical characteristics, morphology and morphogenesis of virions of the causative agent of Crimean hemorrhagic fever.", "content": "Similar physicochemical characteristics were found with strains of Crimean hemorrhagic fever (CHF) and Congo viruses. The particle size, sedimentation coefficient, buoyant density, weight of the particles as well as morphology and morphogenesis of these viruses were similar to those of other members of the Bunyaviridae family. Data are presented on reproduction of CHF virus in cell cultures and on the inner structure of its virion.", "contents": "Physicochemical characteristics, morphology and morphogenesis of virions of the causative agent of Crimean hemorrhagic fever. Similar physicochemical characteristics were found with strains of Crimean hemorrhagic fever (CHF) and Congo viruses. The particle size, sedimentation coefficient, buoyant density, weight of the particles as well as morphology and morphogenesis of these viruses were similar to those of other members of the Bunyaviridae family. Data are presented on reproduction of CHF virus in cell cultures and on the inner structure of its virion."}
{"id": "PMID:18428", "title": "Studies of binding C3-substitute rifamycins to human and bovine serum albumin.", "content": "The interactions of a series of C3-substituted rifamycins with human and bovine serum albumins were studied in order to find possible correlations between the degree of binding and the structural features of the various molecules. The results obtained indicate some of the physicochemical properties and, therefore, of the structural requirements which appear to determine or influence the bonding mechanisms of this series of rifamycins. Two types of interaction were found to exist, ionic and hydrophobic types. The findings suggest that the inhibition by protein of the antibacterial activities of these antibiotics depends on the type of bonding mechanism rather than the degree of binding.", "contents": "Studies of binding C3-substitute rifamycins to human and bovine serum albumin. The interactions of a series of C3-substituted rifamycins with human and bovine serum albumins were studied in order to find possible correlations between the degree of binding and the structural features of the various molecules. The results obtained indicate some of the physicochemical properties and, therefore, of the structural requirements which appear to determine or influence the bonding mechanisms of this series of rifamycins. Two types of interaction were found to exist, ionic and hydrophobic types. The findings suggest that the inhibition by protein of the antibacterial activities of these antibiotics depends on the type of bonding mechanism rather than the degree of binding."}
{"id": "PMID:18429", "title": "On RNA-polymerases of leukemia L 1210 origin and an enzymatic method to screen antitumor antibiotics.", "content": "Four DNA-dependent RNA-polymerases were separated from the cell homogenate of moust leukemia L1210 cell by DEAE-cellulose column chromatography and tentatively designated as Peaks I, II, III and IV in the elution order. Peak II was inactivated by the addition of alpha-amanitin and effects of antibiotics and enzymes on the RNA-polymerase activity using Peaks, I, II and a mixture of Peaks I and II were examined. The RNA-polymerases were used to screen for enzyme inhibitors produced by microbes. This enzymatic method was successfully proved to select antitumor antibiotics.", "contents": "On RNA-polymerases of leukemia L 1210 origin and an enzymatic method to screen antitumor antibiotics. Four DNA-dependent RNA-polymerases were separated from the cell homogenate of moust leukemia L1210 cell by DEAE-cellulose column chromatography and tentatively designated as Peaks I, II, III and IV in the elution order. Peak II was inactivated by the addition of alpha-amanitin and effects of antibiotics and enzymes on the RNA-polymerase activity using Peaks, I, II and a mixture of Peaks I and II were examined. The RNA-polymerases were used to screen for enzyme inhibitors produced by microbes. This enzymatic method was successfully proved to select antitumor antibiotics."}
{"id": "PMID:18426", "title": "Pig plasma benzylamine oxidase: some considerations on the mechanism of the reaction.", "content": "The kinetics of benzaldehyde formation during the oxidation of benzylamine by pig plasma benzylamine oxidase have been studied at different pH values. It has been shown that the first step of the reaction catalyzed by this enzyme is the formation of a Schiff base between the amino group of the substrate and the aldehyde group of the enzyme. Present kinetic studies are consistent with this mechanism and demonstrate the existence of two steps which are alternatively rate-limiting one below pH 6.0, the other above this pH value. The rate-limiting step above pH 6.0 requires the participation of OH-. A mechanism of reaction has been proposed in which the release of products follows the sequence: hydrogen peroxide, aldehyde, ammonia.", "contents": "Pig plasma benzylamine oxidase: some considerations on the mechanism of the reaction. The kinetics of benzaldehyde formation during the oxidation of benzylamine by pig plasma benzylamine oxidase have been studied at different pH values. It has been shown that the first step of the reaction catalyzed by this enzyme is the formation of a Schiff base between the amino group of the substrate and the aldehyde group of the enzyme. Present kinetic studies are consistent with this mechanism and demonstrate the existence of two steps which are alternatively rate-limiting one below pH 6.0, the other above this pH value. The rate-limiting step above pH 6.0 requires the participation of OH-. A mechanism of reaction has been proposed in which the release of products follows the sequence: hydrogen peroxide, aldehyde, ammonia."}
{"id": "PMID:18436", "title": "Oxygen consumption and ventilation of dogs during passive and active exercise.", "content": "A comparison was made between the influence of passive and active exercise on the energy metabolism (EM) and respiratory parameters (RP) of dogs: respiratory minute volume and ventilatory equivalent for O2. Passive exercise was performed in 24 dogs, anesthetized with pentobarbital sodium and morphine or ketamine hydrochloride and pentobarbital sodium, by moving the four limbs at constant frequencies of 25, 45, or 80 movements/min before and after curarization. Active exercise was induced in 35 animals by electric stimulation of the quadriceps and triceps muscles or of the distal ends of femoral and radial nerves at the same frequencies previously indicated. Values obtained for EM and RP during passive exercise were not significantly different from those obtained during resting conditions; active exercise caused a significant increase which was directly proportional to the frequencies of limb movement. Our results indicate that passive muscle movement induces no alteration in O2 consumption and the possible relfexes generated in these experimental conditions were not apparently important on ventilatory control. In active movements, over the range of the frequencies studied, there is a proportional increase in O2 consumption followed by a corresponding increase in ventilation.", "contents": "Oxygen consumption and ventilation of dogs during passive and active exercise. A comparison was made between the influence of passive and active exercise on the energy metabolism (EM) and respiratory parameters (RP) of dogs: respiratory minute volume and ventilatory equivalent for O2. Passive exercise was performed in 24 dogs, anesthetized with pentobarbital sodium and morphine or ketamine hydrochloride and pentobarbital sodium, by moving the four limbs at constant frequencies of 25, 45, or 80 movements/min before and after curarization. Active exercise was induced in 35 animals by electric stimulation of the quadriceps and triceps muscles or of the distal ends of femoral and radial nerves at the same frequencies previously indicated. Values obtained for EM and RP during passive exercise were not significantly different from those obtained during resting conditions; active exercise caused a significant increase which was directly proportional to the frequencies of limb movement. Our results indicate that passive muscle movement induces no alteration in O2 consumption and the possible relfexes generated in these experimental conditions were not apparently important on ventilatory control. In active movements, over the range of the frequencies studied, there is a proportional increase in O2 consumption followed by a corresponding increase in ventilation."}
{"id": "PMID:18437", "title": "Rate of pH changes in blood plasma in vitro and in vivo.", "content": "The rate of pH decrease in dog blood after addition of CO2 (dissolved in saline) was measured in vitro with a combination pH electrode and fast-response amplifier. The pH change was found to have an apparent half time of 6.0 +/- 0.5 s at 38 degrees C, similar to that predicted by previous mathematical simulations on the basis of uncatalyzed CO2 hydration kinetics and the buffering characteristics of plasma. Measurements were also made in vivo in dogs by withdrawing blood rapidly from a carotid artery through a temperature-controlled chamber containing a pH electrode. When the flow was stopped, we measured the pH change which occurs in blood (after it leaves the lungs) as the slow dehydration of bicarbonate continues. The measured half time was 7.3 +/- 0.6 s, again agreeing well with predictions. Essentially the same half time was found when the direction of approach to chemical equilibrium was reversed by adding CO2 to the inspired air. The rate of the reactions could be increased markedly by hemolyzing the blood to release carbonic anhydrase into the plasma.", "contents": "Rate of pH changes in blood plasma in vitro and in vivo. The rate of pH decrease in dog blood after addition of CO2 (dissolved in saline) was measured in vitro with a combination pH electrode and fast-response amplifier. The pH change was found to have an apparent half time of 6.0 +/- 0.5 s at 38 degrees C, similar to that predicted by previous mathematical simulations on the basis of uncatalyzed CO2 hydration kinetics and the buffering characteristics of plasma. Measurements were also made in vivo in dogs by withdrawing blood rapidly from a carotid artery through a temperature-controlled chamber containing a pH electrode. When the flow was stopped, we measured the pH change which occurs in blood (after it leaves the lungs) as the slow dehydration of bicarbonate continues. The measured half time was 7.3 +/- 0.6 s, again agreeing well with predictions. Essentially the same half time was found when the direction of approach to chemical equilibrium was reversed by adding CO2 to the inspired air. The rate of the reactions could be increased markedly by hemolyzing the blood to release carbonic anhydrase into the plasma."}
{"id": "PMID:18438", "title": "Urease of Klebsiella aerogenes: control of its synthesis by glutamine synthetase.", "content": "Urease was purified 24-fold from extracts of Klebsiella aerogenes. The enzyme has a molecular weight of 230,000 as determined by gel filtration, is highly substrate specific, and has a Km for urea of 0.7 mM. A mutant strain lacking urease was isolated; it failed to grow with urea as the sole source of nitrogen but did grow on media containing other nitrogen sources such as ammonia, histidine, or arginine. Urease was present at a high level when the cells were starved for nitrogen; its synthesis was repressed when the external ammonia concentration was high. Formation of urease did not require induction by urea and was not subject to catabolite repression. Its synthesis was controlled by glutamine synthetase. Mutants lacking glutamine synthetase failed to produce urease, and mutants forming glutamine synthetase at a high constitutive level also formed urease constitutively. Thus, the formation of urease is regulated like that of other enzymes of K. aerogenes capable of supplying the cell with ammonia or glutamate.", "contents": "Urease of Klebsiella aerogenes: control of its synthesis by glutamine synthetase. Urease was purified 24-fold from extracts of Klebsiella aerogenes. The enzyme has a molecular weight of 230,000 as determined by gel filtration, is highly substrate specific, and has a Km for urea of 0.7 mM. A mutant strain lacking urease was isolated; it failed to grow with urea as the sole source of nitrogen but did grow on media containing other nitrogen sources such as ammonia, histidine, or arginine. Urease was present at a high level when the cells were starved for nitrogen; its synthesis was repressed when the external ammonia concentration was high. Formation of urease did not require induction by urea and was not subject to catabolite repression. Its synthesis was controlled by glutamine synthetase. Mutants lacking glutamine synthetase failed to produce urease, and mutants forming glutamine synthetase at a high constitutive level also formed urease constitutively. Thus, the formation of urease is regulated like that of other enzymes of K. aerogenes capable of supplying the cell with ammonia or glutamate."}
{"id": "PMID:18439", "title": "Fermentative metabolism of pyruvate by Rhodospirillum rubrum after anaerobic growth in darkness.", "content": "Rhodospirillum rubrum grew anaerobically in darkness and fermented sodium pyruvate by a pyruvate formate-lyase reaction. During 30 min of anaerobic dark or light incubation with sodium pyrivate, crude extracts from fermentatively grown cells produced about 6 micronmol of acetylphosphate and formate per mg of protein in reactions performed at pH 8.3. Cell extracts also catalyzed the exchange of sodium [14C]formate into sodium pyruvate at an apparent pH optimum of 7.3 to 7.5, but only about 2.5 micronmol of acetylphosphate was produced at this lower pH value. R. rubrum may also form pyruvate:ferredoxin oxidoreductase activity, as evidenced by low bicarbonate exchange activity. However, its participation in pyruvate metabolism in anaerobic dark-grown cells was not understood. During anaerobic, dark growth with pyruvate, formate was an intermediate in H2 and CO2 gas evolution. In contrast with H2 production by a light-dependent H2-nitrogenase system in photosynthetically grown cells, H2 formation in fermenting R. rubrum occurred through a carbon monoxide-sensitive formic hydrogenlyase reaction not influenced by light.", "contents": "Fermentative metabolism of pyruvate by Rhodospirillum rubrum after anaerobic growth in darkness. Rhodospirillum rubrum grew anaerobically in darkness and fermented sodium pyruvate by a pyruvate formate-lyase reaction. During 30 min of anaerobic dark or light incubation with sodium pyrivate, crude extracts from fermentatively grown cells produced about 6 micronmol of acetylphosphate and formate per mg of protein in reactions performed at pH 8.3. Cell extracts also catalyzed the exchange of sodium [14C]formate into sodium pyruvate at an apparent pH optimum of 7.3 to 7.5, but only about 2.5 micronmol of acetylphosphate was produced at this lower pH value. R. rubrum may also form pyruvate:ferredoxin oxidoreductase activity, as evidenced by low bicarbonate exchange activity. However, its participation in pyruvate metabolism in anaerobic dark-grown cells was not understood. During anaerobic, dark growth with pyruvate, formate was an intermediate in H2 and CO2 gas evolution. In contrast with H2 production by a light-dependent H2-nitrogenase system in photosynthetically grown cells, H2 formation in fermenting R. rubrum occurred through a carbon monoxide-sensitive formic hydrogenlyase reaction not influenced by light."}
{"id": "PMID:18440", "title": "Characterization of an endonuclease associated with the drug resistance plasmid pKM101.", "content": "An endonuclease was detected in strains of Salmonella typhimurium containing the drug resistance plasmid pKM101. The enzyme was not detectable in strains lacking this plasmid, but it was present in strains containing mutants of pKM101 that were no longer able to enhance host cell mutagenesis. The endonuclease had a molecular weight of roughly 75,000 and, at pH 7.0, was equally active on single-stranded and duplex deoxyribonucleic acid (DNA). The reaction with single-stranded DNA was optimal at pH 5.5, whereas with duplex DNA the optimum was pH 6.8. The enzyme required a divalent cation for activity, and it had no detectable exonuclease activity with single-stranded or duplex DNA. The endonuclease extensively degraded DNA with no apparent base specificity, forming 5'-phosphomonoester termini. Although characterization of the endonuclease has not revealed its function, the enzyme does not appear to be a restriction endonuclease.", "contents": "Characterization of an endonuclease associated with the drug resistance plasmid pKM101. An endonuclease was detected in strains of Salmonella typhimurium containing the drug resistance plasmid pKM101. The enzyme was not detectable in strains lacking this plasmid, but it was present in strains containing mutants of pKM101 that were no longer able to enhance host cell mutagenesis. The endonuclease had a molecular weight of roughly 75,000 and, at pH 7.0, was equally active on single-stranded and duplex deoxyribonucleic acid (DNA). The reaction with single-stranded DNA was optimal at pH 5.5, whereas with duplex DNA the optimum was pH 6.8. The enzyme required a divalent cation for activity, and it had no detectable exonuclease activity with single-stranded or duplex DNA. The endonuclease extensively degraded DNA with no apparent base specificity, forming 5'-phosphomonoester termini. Although characterization of the endonuclease has not revealed its function, the enzyme does not appear to be a restriction endonuclease."}
{"id": "PMID:18441", "title": "Enzymatic reduction of mercurous ions in Escherichia coli bearing R factor.", "content": "Mercurous ion (Hg(+))-dependent reduced nicotinamide adenine dinucleotide phosphate oxidation was demonstrated in an extract from cells of Escherichia coli W2252 that bear R factor.", "contents": "Enzymatic reduction of mercurous ions in Escherichia coli bearing R factor. Mercurous ion (Hg(+))-dependent reduced nicotinamide adenine dinucleotide phosphate oxidation was demonstrated in an extract from cells of Escherichia coli W2252 that bear R factor."}
{"id": "PMID:18446", "title": "Base specificity of polyamine binding to synthetic polynucleotides.", "content": "The binding of polyamines and magnesium to synthetic polynucleotides has been studied by gel filtration on a Sephadex G-50 column. Among the single-stranded polynucleotides examined [poly(A), poly(C), and poly(U)], polyamines were found to bind to poly(C) and poly(U) preferentially, while the binding of Mg2+ was greatest with poly(A). Spermine bound to poly(U) was displaced completely by NH4+ but incompletely by Mg2+, while Mg2+ bound to poly(A) was displaced completely be spermine but incompletely by NH4+. The optimal pH for the binding of spermine to poly(U) was found to be about 7.9, while Mg2+ could bind to poly(A) over a broad pH range (7.1--8.7).", "contents": "Base specificity of polyamine binding to synthetic polynucleotides. The binding of polyamines and magnesium to synthetic polynucleotides has been studied by gel filtration on a Sephadex G-50 column. Among the single-stranded polynucleotides examined [poly(A), poly(C), and poly(U)], polyamines were found to bind to poly(C) and poly(U) preferentially, while the binding of Mg2+ was greatest with poly(A). Spermine bound to poly(U) was displaced completely by NH4+ but incompletely by Mg2+, while Mg2+ bound to poly(A) was displaced completely be spermine but incompletely by NH4+. The optimal pH for the binding of spermine to poly(U) was found to be about 7.9, while Mg2+ could bind to poly(A) over a broad pH range (7.1--8.7)."}
{"id": "PMID:18447", "title": "Morphology of lipid micelles containing lysolecithin.", "content": "Mixtures of lysolecithin with various phospholipids were studied by electron microscopy using negative staining. Mixtures of dipalmitoyllecithin and lysolecithin produced disc-shaped structures which were stacked in aggregates with a 6.0--6.4 nm repeat. The disc were 10--50 nm in diameter. The disc-shaped structures were best observed in equimolar mixtures of dipalmitoyllecithin and lysolecithin. When dipalmitoyllecithin was replaced by dimyristoyllecithin, the structures were rather different from those observed in the system containing dipalmitoyllecithin; a cylindrical micellar phase was predominant. Equimolar mixtures of egg lecithin and lysolecithin formed the more usual smectic, concentric lamellae (liposomes) and elongated rod-like micelles which might be bimolecular fragments of spherules. The radius of the rod-like micelles was about 6 nm. Structures of rod-like micelles were observed more frequently in the samples after incubation at room temperature and then further incubation at 0 degrees C. Equimolar mixtures of didecanoyllecithin and lysolecithin produced large amounts of elongated rod-like micelles. Beef brain sphingoymyelin showed disc-shaped structures when mixed with lysolecithin. Incorporation of cholesterol into the mixtures of dipalmitoyllecithin and lysolecithin changed the morphological structure; the size of the disc became larger and eventually liposomes were formed with an increase of cholesterol content. The structures observed in mixtures of dipalmitoyllecithin or sphingomyelin and lysolecithin closely resembled those observed in complexes of apolipoprotein and lipid.", "contents": "Morphology of lipid micelles containing lysolecithin. Mixtures of lysolecithin with various phospholipids were studied by electron microscopy using negative staining. Mixtures of dipalmitoyllecithin and lysolecithin produced disc-shaped structures which were stacked in aggregates with a 6.0--6.4 nm repeat. The disc were 10--50 nm in diameter. The disc-shaped structures were best observed in equimolar mixtures of dipalmitoyllecithin and lysolecithin. When dipalmitoyllecithin was replaced by dimyristoyllecithin, the structures were rather different from those observed in the system containing dipalmitoyllecithin; a cylindrical micellar phase was predominant. Equimolar mixtures of egg lecithin and lysolecithin formed the more usual smectic, concentric lamellae (liposomes) and elongated rod-like micelles which might be bimolecular fragments of spherules. The radius of the rod-like micelles was about 6 nm. Structures of rod-like micelles were observed more frequently in the samples after incubation at room temperature and then further incubation at 0 degrees C. Equimolar mixtures of didecanoyllecithin and lysolecithin produced large amounts of elongated rod-like micelles. Beef brain sphingoymyelin showed disc-shaped structures when mixed with lysolecithin. Incorporation of cholesterol into the mixtures of dipalmitoyllecithin and lysolecithin changed the morphological structure; the size of the disc became larger and eventually liposomes were formed with an increase of cholesterol content. The structures observed in mixtures of dipalmitoyllecithin or sphingomyelin and lysolecithin closely resembled those observed in complexes of apolipoprotein and lipid."}
{"id": "PMID:18448", "title": "Affinity labeling of adenine nucleotide-related enzymes with reactive adenine nucleotide analogs. I. Affinity labeling of glyceraldehyde 3-phosphate dehydrogenase and myokinase with a reactive AMP analog.", "content": "Rabbit muscle glyceraldehyde 3-phosphate dehydrogenase (GPD) and myokinase (MK) were rapidly inactivated by  a reactive AMP analog, N6-(p-bromoacetaminobenzyl)-AMP, under mild conditions. Complete inactivation was observed when 4 and 0.3 mol of the reagent with respect to enzyme were reacted with GPD and MK, respectively. The inactivation of both enzymes were favored at higher pH and the enzymes were protected by addition of adenine nucleotide substrate. Modified GPD or MK had no affinity for AMP-Sepharose, in contrast to the native enzymes. From these results, the inactivation of GPD and MK by the reactive AMP analog can be regarded as an affinity labeling. The posibility that the present AMP analog may be used as a general affinity labeling reagent for various adenine nucleotide-related enzymes is discussed based on the results obtained.", "contents": "Affinity labeling of adenine nucleotide-related enzymes with reactive adenine nucleotide analogs. I. Affinity labeling of glyceraldehyde 3-phosphate dehydrogenase and myokinase with a reactive AMP analog. Rabbit muscle glyceraldehyde 3-phosphate dehydrogenase (GPD) and myokinase (MK) were rapidly inactivated by  a reactive AMP analog, N6-(p-bromoacetaminobenzyl)-AMP, under mild conditions. Complete inactivation was observed when 4 and 0.3 mol of the reagent with respect to enzyme were reacted with GPD and MK, respectively. The inactivation of both enzymes were favored at higher pH and the enzymes were protected by addition of adenine nucleotide substrate. Modified GPD or MK had no affinity for AMP-Sepharose, in contrast to the native enzymes. From these results, the inactivation of GPD and MK by the reactive AMP analog can be regarded as an affinity labeling. The posibility that the present AMP analog may be used as a general affinity labeling reagent for various adenine nucleotide-related enzymes is discussed based on the results obtained."}
{"id": "PMID:18442", "title": "Survey for alpha-(1 leads to 3)-glucanase activity among yeasts.", "content": "Activity of alpha-(1 leads to 3)-glucanase was found in species of Cryptococcus, Rhodotorula, and Endomyces. Observations on the expression and stability of this enzyme in Rhodotorula minuta var. texensis was presented.", "contents": "Survey for alpha-(1 leads to 3)-glucanase activity among yeasts. Activity of alpha-(1 leads to 3)-glucanase was found in species of Cryptococcus, Rhodotorula, and Endomyces. Observations on the expression and stability of this enzyme in Rhodotorula minuta var. texensis was presented."}
{"id": "PMID:18449", "title": "Stereochemical studies of hydrogen incorporation from nucleotides with fatty acid synthetase from Brevibacterium ammoniagenes.", "content": "The biosynthesis of fatty acids from malonyl-CoA and acetyl-CoA was investigated with an enzyme preparation which was purified 100-fold from Brevibacterium ammoniagenes. Fatty acids synthesized in the presence of D2O and stereospecifically deuterated NADPH and NADH were isolated and analyzed by mass chromatography to examine the localization of deuterium in the molecule. The following results were obtained: 1) HB hydrogen of NADPH was used for beta-ketoacyl reductase. 2) HB hydrogen of NADH was used  for enoyl reductase. 3) Hydrogen atoms from water were found on the even-numbered methylene carbon atoms (2-hydrogen atoms per carbon atom) and some were also found on the odd-numbered methylene carbon atoms. 4) Hydrogen atoms from NADPH was found on the odd-numbered methylene carbon atoms (1 hydrogen per carbon). 5) Hydrogen atoms from NADH was also found on the odd-numbered methylene carbon atoms, but the number of incorporated hydrogen atoms was less than expected. The exchange of HB hydrogen of NADH with water catalyzed by enoyl reductase was suspected. 6) The exchange of methylene hydrogen atoms of malonyl-CoA with protons of water was suggested by 13C NMR analysis.", "contents": "Stereochemical studies of hydrogen incorporation from nucleotides with fatty acid synthetase from Brevibacterium ammoniagenes. The biosynthesis of fatty acids from malonyl-CoA and acetyl-CoA was investigated with an enzyme preparation which was purified 100-fold from Brevibacterium ammoniagenes. Fatty acids synthesized in the presence of D2O and stereospecifically deuterated NADPH and NADH were isolated and analyzed by mass chromatography to examine the localization of deuterium in the molecule. The following results were obtained: 1) HB hydrogen of NADPH was used for beta-ketoacyl reductase. 2) HB hydrogen of NADH was used  for enoyl reductase. 3) Hydrogen atoms from water were found on the even-numbered methylene carbon atoms (2-hydrogen atoms per carbon atom) and some were also found on the odd-numbered methylene carbon atoms. 4) Hydrogen atoms from NADPH was found on the odd-numbered methylene carbon atoms (1 hydrogen per carbon). 5) Hydrogen atoms from NADH was also found on the odd-numbered methylene carbon atoms, but the number of incorporated hydrogen atoms was less than expected. The exchange of HB hydrogen of NADH with water catalyzed by enoyl reductase was suspected. 6) The exchange of methylene hydrogen atoms of malonyl-CoA with protons of water was suggested by 13C NMR analysis."}
{"id": "PMID:18450", "title": "Chemical modifications of ribonuclease U1.", "content": "In order to obtain information on the nature of the amino acid residues involved in the activity of ribonuclease U1 [EC 3.1.4.8], various chemical modifications of the enzyme were carried out. RNase U1 was inactivated by reaction with iodoacetate at pH 5.5 with concomitant incorporation of 1 carboxymethyl group per molecule of the enzyme. The residue specifically modified by iodoacetate was identified as one of the glutamic acid residues, as in the case of RNase T1. The enzyme was also inactivated extensively by reaction with iodoacetamide at pH 8.0 with the loss of about one residue each of histidine and lysine. When RNase U1 was treated with a large excess of phenylglyoxal, the enzymatic activity and binding ability toward 3'-GMP were lost, with simultaneous modification of about 1 residue of arginine. The reaction of citraconic anhydride with RNase U1 led to the loss of enzymatic activity and modification of about 1 residue of lysine. The inactivated enzyme, however, retained binding ability toward 3'-GMP. These results indicate that there are marked similarities in the active sites of RNases T1 and U1.", "contents": "Chemical modifications of ribonuclease U1. In order to obtain information on the nature of the amino acid residues involved in the activity of ribonuclease U1 [EC 3.1.4.8], various chemical modifications of the enzyme were carried out. RNase U1 was inactivated by reaction with iodoacetate at pH 5.5 with concomitant incorporation of 1 carboxymethyl group per molecule of the enzyme. The residue specifically modified by iodoacetate was identified as one of the glutamic acid residues, as in the case of RNase T1. The enzyme was also inactivated extensively by reaction with iodoacetamide at pH 8.0 with the loss of about one residue each of histidine and lysine. When RNase U1 was treated with a large excess of phenylglyoxal, the enzymatic activity and binding ability toward 3'-GMP were lost, with simultaneous modification of about 1 residue of arginine. The reaction of citraconic anhydride with RNase U1 led to the loss of enzymatic activity and modification of about 1 residue of lysine. The inactivated enzyme, however, retained binding ability toward 3'-GMP. These results indicate that there are marked similarities in the active sites of RNases T1 and U1."}
{"id": "PMID:18451", "title": "Purification and some properties of cyclohexylamine oxidase from a Pseudomonas sp.", "content": "Cyclohexylamine oxidase was purified 90-fold from cell-free extracts of Pseudomonas sp. capable of assimilating sodium cyclamate. The purified enzyme was homogeneous in disc electrophoresis, and the molecular weight was found to be approximately 80,000 by gel filtration. The enzyme catalyzed the following reaction: cyclohexylamine+O2+H2O leads to cyclohexanone+NH3+H2O2. The enzyme thus can be classified as an amine oxidase; it utilized oxygen as the ultimate electron acceptor. The pH optimum of the reaction was 6.8 and the apparent Km value for cyclohexylamine was 2.5 X 10(-4) M. The enzyme was highly specific for the deamination of alicyclic primary amines such as cyclohexylamine, but was found to be inactive toward ordinary amines used as substrates for amine oxidases. The enzyme solution was yellow in color and showed a typical flavoprotein spectrum; the addition of cyclohexylamine under anaerobic conditions caused reduction of the flavin in the native enzyme. The flavin of the prosthetic group was identified as FAD by thin layer chromatography. The participation of sulfhydryl groups in the enzymic action was also suggested by the observation that the enzyme activity was inhibited in the presence of PCMB and could be recovered by the addition of glutathione.", "contents": "Purification and some properties of cyclohexylamine oxidase from a Pseudomonas sp. Cyclohexylamine oxidase was purified 90-fold from cell-free extracts of Pseudomonas sp. capable of assimilating sodium cyclamate. The purified enzyme was homogeneous in disc electrophoresis, and the molecular weight was found to be approximately 80,000 by gel filtration. The enzyme catalyzed the following reaction: cyclohexylamine+O2+H2O leads to cyclohexanone+NH3+H2O2. The enzyme thus can be classified as an amine oxidase; it utilized oxygen as the ultimate electron acceptor. The pH optimum of the reaction was 6.8 and the apparent Km value for cyclohexylamine was 2.5 X 10(-4) M. The enzyme was highly specific for the deamination of alicyclic primary amines such as cyclohexylamine, but was found to be inactive toward ordinary amines used as substrates for amine oxidases. The enzyme solution was yellow in color and showed a typical flavoprotein spectrum; the addition of cyclohexylamine under anaerobic conditions caused reduction of the flavin in the native enzyme. The flavin of the prosthetic group was identified as FAD by thin layer chromatography. The participation of sulfhydryl groups in the enzymic action was also suggested by the observation that the enzyme activity was inhibited in the presence of PCMB and could be recovered by the addition of glutathione."}
{"id": "PMID:18455", "title": "Purification and properties of phenylalanine ammonia-lyase in cut-injured sweet potato.", "content": "L-Phenylalanine ammonia-lyase (PAL) activity was developed in response to cut injury in sweet potato root tissue. The enzyme was purified from tissue incubated for 1 day after slicing by ammonium sulfate fractionation, column chromatographies on L-phenylalanyl Sepharose 4B, phosphocellulose. Sephadex G-200 and Sepharose 6B and preparative polyacrylamide gel electrophoresis. The molecular weight and sedimentation coefficient were estimated to be 285,000 to 320,000 and 11.6 to 11.9 S, respectively. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gel yielded a single stained protein band which corresponded to a subunit weight of 80,000. Thus, the enzyme seems to be composed of four subunits of the same size. Neither L-tyrosine nor D-phenylalanine served as a substrate. Two Km values for the PAL were observed above and below 30 micrometers at various temperatures and were lower than those for PALs of other plants. The slope of the Arrhenius plot had a discontinuity at 17 degrees C. The values of activation energy were calculated to be 15,000 cal and 19,000 cal above and below 17 degrees C, respectively. Similar discontinuities were also observed in the effect of temperature on the Km values and the Hill coefficients. Negative cooperativity was observed at 10 degrees C (n = 0.83), but was not marked above 20 degrees C (n = 0.94).", "contents": "Purification and properties of phenylalanine ammonia-lyase in cut-injured sweet potato. L-Phenylalanine ammonia-lyase (PAL) activity was developed in response to cut injury in sweet potato root tissue. The enzyme was purified from tissue incubated for 1 day after slicing by ammonium sulfate fractionation, column chromatographies on L-phenylalanyl Sepharose 4B, phosphocellulose. Sephadex G-200 and Sepharose 6B and preparative polyacrylamide gel electrophoresis. The molecular weight and sedimentation coefficient were estimated to be 285,000 to 320,000 and 11.6 to 11.9 S, respectively. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gel yielded a single stained protein band which corresponded to a subunit weight of 80,000. Thus, the enzyme seems to be composed of four subunits of the same size. Neither L-tyrosine nor D-phenylalanine served as a substrate. Two Km values for the PAL were observed above and below 30 micrometers at various temperatures and were lower than those for PALs of other plants. The slope of the Arrhenius plot had a discontinuity at 17 degrees C. The values of activation energy were calculated to be 15,000 cal and 19,000 cal above and below 17 degrees C, respectively. Similar discontinuities were also observed in the effect of temperature on the Km values and the Hill coefficients. Negative cooperativity was observed at 10 degrees C (n = 0.83), but was not marked above 20 degrees C (n = 0.94)."}
{"id": "PMID:18457", "title": "The behavior of 9-aminoacridine as an indicator of transmembrane pH difference in liposomes of natural bacterial phospholipids.", "content": "The behavior of 9-aminoacridine as an indicator of pH differences artificially set across a membrane has been reexamined in liposomes prepared from bacterial phospholipids extracted from chromatophores of Rhodopseudomonas capsulata grown photoheterotrophically. The dye behaves as an ideal indicator for pH differences lower than about three units; at higher pH's the expected linear dependence of Q/(100-Q) vs. pH is no longer strictly observed. Similarly a linear dependence upon the volume of the liposomes added has been verified. The amine ceases to respond to pH changes when the pH of the external medium exceeds the value of 10, corresponsing to the pKa of 9-aminoacridine. The apparent volume of the inner phase of liposomes, as calculated from fluorescence quenching, but not the slope of dependence of fluorescence on pH, appears to be affected by several factors, including the ionic composition, the osmolarity of the external medium, and the microscopic structure of the liposomes. Millimolar concentrations of earth-alkaline cations diminish the apparent internal volume of liposomes, in agreement with the complexing effect of these ions on phospholipid bilayers. The osmotic response of the apparent inner volume has also been verified; this parameter decreases linearly with the reciprocal of the external osmolarity, as expected from the van't Hoff relation; an osmolarity exceeding 0.3 M is, however, necessary in order to observe this effect.", "contents": "The behavior of 9-aminoacridine as an indicator of transmembrane pH difference in liposomes of natural bacterial phospholipids. The behavior of 9-aminoacridine as an indicator of pH differences artificially set across a membrane has been reexamined in liposomes prepared from bacterial phospholipids extracted from chromatophores of Rhodopseudomonas capsulata grown photoheterotrophically. The dye behaves as an ideal indicator for pH differences lower than about three units; at higher pH's the expected linear dependence of Q/(100-Q) vs. pH is no longer strictly observed. Similarly a linear dependence upon the volume of the liposomes added has been verified. The amine ceases to respond to pH changes when the pH of the external medium exceeds the value of 10, corresponsing to the pKa of 9-aminoacridine. The apparent volume of the inner phase of liposomes, as calculated from fluorescence quenching, but not the slope of dependence of fluorescence on pH, appears to be affected by several factors, including the ionic composition, the osmolarity of the external medium, and the microscopic structure of the liposomes. Millimolar concentrations of earth-alkaline cations diminish the apparent internal volume of liposomes, in agreement with the complexing effect of these ions on phospholipid bilayers. The osmotic response of the apparent inner volume has also been verified; this parameter decreases linearly with the reciprocal of the external osmolarity, as expected from the van't Hoff relation; an osmolarity exceeding 0.3 M is, however, necessary in order to observe this effect."}
{"id": "PMID:18462", "title": "CDP-diglyceride:inositol transferase from rat liver. Purification and properties.", "content": "CDP-diglyceride:inositol transferase, which catalyzes the final step of the de novo synthesis of phosphatidylinositol, was solubilized by sodium cholate from microsomes prepared from rat liver and purified by ammonium sulfate fractionation, sucrose density gradient centrifugation, and DEAE-cellulose column chromatography. Addition of phospholipid during the purification and the assay procedures prevented irreversible loss of the enzyme activity to some extent. The resulting preparation was nearly homogeneous as judged by polyacrylamide gel electrophoresis. The recovery of the purified enzyme from the microsomal fraction was 3 to 3.3% with respect to activity and 0.12% with respect to amount of protein. The molecular weight of the enzyme was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 60,000. The purified enzyme required exogenous phospholipds for its activity. Various phospholipid classes activated the enzyme rather nonspecifically. The Km for myo-inositol was 2.5 X 10(-3) M and that for CDP-diglyceride was 1.7 X 10(-4) M. The pH optimum was 8.6. The enzyme required Mm2+ or Mg2+ for activity. The optimal concentration of Mn2+ for activation was 0.5 mM, while the activity in the presence of Mg2+ increased up to 20 mM. The enzyme was inhibited by thiol-reactive reagents. There was a competition for inositol by inosose-2 but not by scyllitol.", "contents": "CDP-diglyceride:inositol transferase from rat liver. Purification and properties. CDP-diglyceride:inositol transferase, which catalyzes the final step of the de novo synthesis of phosphatidylinositol, was solubilized by sodium cholate from microsomes prepared from rat liver and purified by ammonium sulfate fractionation, sucrose density gradient centrifugation, and DEAE-cellulose column chromatography. Addition of phospholipid during the purification and the assay procedures prevented irreversible loss of the enzyme activity to some extent. The resulting preparation was nearly homogeneous as judged by polyacrylamide gel electrophoresis. The recovery of the purified enzyme from the microsomal fraction was 3 to 3.3% with respect to activity and 0.12% with respect to amount of protein. The molecular weight of the enzyme was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 60,000. The purified enzyme required exogenous phospholipds for its activity. Various phospholipid classes activated the enzyme rather nonspecifically. The Km for myo-inositol was 2.5 X 10(-3) M and that for CDP-diglyceride was 1.7 X 10(-4) M. The pH optimum was 8.6. The enzyme required Mm2+ or Mg2+ for activity. The optimal concentration of Mn2+ for activation was 0.5 mM, while the activity in the presence of Mg2+ increased up to 20 mM. The enzyme was inhibited by thiol-reactive reagents. There was a competition for inositol by inosose-2 but not by scyllitol."}
{"id": "PMID:18463", "title": "Characterization of the glutamine site of Escherichia coli guanosine 5'-monophosphate synthetase.", "content": "Alkylation of guanosine 5'-monophosphate (GMP) synthetase with the glutamine analogs L-2-amino-4-oxo-5-chloropentanoic acid (chloroketon) and 6-diazo-5-oxonorleucine (DON) inactivated glutamine- and NH3-dependent GMP synthetase. Inactivation exhibited second order kinetics. Complete inactivation was accompanied by covalent attachment of 0.4 to 0.5 equivalent of chloroketon/subunit. Alkylation of GMP synthetase with iodacetamide selectively inactivated glutamine-dependent activity. The NH3-dependent activity was relatively unaffected. Approximately 1 equivalent of carboxamidomethyl group was incorporated per subunit. Carboxymethylcysteine was the only modified amino acid hydrolysis. Prior treatment with chloroketone decreased the capacity for alkylation by iodacetamide, suggesting that both reagents alkylate the  same residue. GMP synthetase exhibits glutaminase activity when ATP is replaced by adenosine plus PPi. Iodoacetamide inactivates glutaminase concomitant with glutamine-dependent GMP synthetase. Analysis of pH versus velocity and Km data indicates that the amide of glutamine remains enzyme bound and does not mix with exogenous NH3 in the synthesis of GMP.", "contents": "Characterization of the glutamine site of Escherichia coli guanosine 5'-monophosphate synthetase. Alkylation of guanosine 5'-monophosphate (GMP) synthetase with the glutamine analogs L-2-amino-4-oxo-5-chloropentanoic acid (chloroketon) and 6-diazo-5-oxonorleucine (DON) inactivated glutamine- and NH3-dependent GMP synthetase. Inactivation exhibited second order kinetics. Complete inactivation was accompanied by covalent attachment of 0.4 to 0.5 equivalent of chloroketon/subunit. Alkylation of GMP synthetase with iodacetamide selectively inactivated glutamine-dependent activity. The NH3-dependent activity was relatively unaffected. Approximately 1 equivalent of carboxamidomethyl group was incorporated per subunit. Carboxymethylcysteine was the only modified amino acid hydrolysis. Prior treatment with chloroketone decreased the capacity for alkylation by iodacetamide, suggesting that both reagents alkylate the  same residue. GMP synthetase exhibits glutaminase activity when ATP is replaced by adenosine plus PPi. Iodoacetamide inactivates glutaminase concomitant with glutamine-dependent GMP synthetase. Analysis of pH versus velocity and Km data indicates that the amide of glutamine remains enzyme bound and does not mix with exogenous NH3 in the synthesis of GMP."}
{"id": "PMID:18464", "title": "Nature of the lectin-induced activation of plasma membrane Mg2+ATPase.", "content": "The Mg2+ATPase activity of liver plasma membranes decreases markedly with increasing temperature above 30 degrees. This negative temperature dependency is counteracted by the binding of wheat germ agglutinin, concanavalin A, or Ricinus communis agglutinin (at concentrations greater than or equal 0.5 mg/ml) to membranes prior to assay of the enzyme. With one of these lectins bound, the enzyme has a single energy of activation between 20 degrees and 45 degrees. The binding of dimeric succinyl concanavalin A, soybean agglutinin, fucose-binding lectin from Lotus tetragonolobus, or the leucoagglutinin from Phaseolus vulgaris does not alter the temperature dependency of the enzyme. The latter two lectins, however, do prevent the concanavalin A-induced activation of the enzyme at 37 degrees. At saturating substrate concentrations, the enzyme is not inhibited by any of the lectins tested over a wide range of concentrations. Cytochalasin B and colchicine separately or in combination have little influence on the lectin-induced enhancement of enzyme activity. Chlorpromazine and vinblastine sulfate each partially prevent the activation and in combination do so completely. Treatment of the membranes with the detergent Lubrol-PX or phospholipase A prevents activation of the enzyme by concanavalin A. The results are consistent with a restriction by the lectin of an environment which is normally too disordered for maximal enzyme activity above 30 degrees.", "contents": "Nature of the lectin-induced activation of plasma membrane Mg2+ATPase. The Mg2+ATPase activity of liver plasma membranes decreases markedly with increasing temperature above 30 degrees. This negative temperature dependency is counteracted by the binding of wheat germ agglutinin, concanavalin A, or Ricinus communis agglutinin (at concentrations greater than or equal 0.5 mg/ml) to membranes prior to assay of the enzyme. With one of these lectins bound, the enzyme has a single energy of activation between 20 degrees and 45 degrees. The binding of dimeric succinyl concanavalin A, soybean agglutinin, fucose-binding lectin from Lotus tetragonolobus, or the leucoagglutinin from Phaseolus vulgaris does not alter the temperature dependency of the enzyme. The latter two lectins, however, do prevent the concanavalin A-induced activation of the enzyme at 37 degrees. At saturating substrate concentrations, the enzyme is not inhibited by any of the lectins tested over a wide range of concentrations. Cytochalasin B and colchicine separately or in combination have little influence on the lectin-induced enhancement of enzyme activity. Chlorpromazine and vinblastine sulfate each partially prevent the activation and in combination do so completely. Treatment of the membranes with the detergent Lubrol-PX or phospholipase A prevents activation of the enzyme by concanavalin A. The results are consistent with a restriction by the lectin of an environment which is normally too disordered for maximal enzyme activity above 30 degrees."}
{"id": "PMID:18467", "title": "Purification of human erythropoietin.", "content": "Human erythropoietin, derived from urine of patients with aplastic anemia, has been purified to apparent homogeneity. The seven-step procedure, which included ion exchange chromatography, ethanol precipitation, gel filtration, and adsorption chromatography, yielded a preparation with a potency of 70,400 units/mg of protein in 21% yield. This represents a purification factor of 930. The purified hormone has a single electrophoretic component in polyacrylamide gels at pH 9, in the presence of sodium dodecylsulfate at pH 7, and in the presence of Triton X-100 at pH 6. Two fractions of the same potency and molecular size, by sodium dodecyl sulfate gel electrophoresis, but differing slightly in mobility at pH 9, were obtained at the last step of fractionation. The nature of the difference between these two components is not yet understood.", "contents": "Purification of human erythropoietin. Human erythropoietin, derived from urine of patients with aplastic anemia, has been purified to apparent homogeneity. The seven-step procedure, which included ion exchange chromatography, ethanol precipitation, gel filtration, and adsorption chromatography, yielded a preparation with a potency of 70,400 units/mg of protein in 21% yield. This represents a purification factor of 930. The purified hormone has a single electrophoretic component in polyacrylamide gels at pH 9, in the presence of sodium dodecylsulfate at pH 7, and in the presence of Triton X-100 at pH 6. Two fractions of the same potency and molecular size, by sodium dodecyl sulfate gel electrophoresis, but differing slightly in mobility at pH 9, were obtained at the last step of fractionation. The nature of the difference between these two components is not yet understood."}
{"id": "PMID:18468", "title": "Kinetic mechanism of tRNA nucleotidyltransferase from Escherichia coli.", "content": "A kinetic analysis of the incorporation of AMP into tRNA lacking the 3'-terminal residue by tRNA nucleotidyltransferase (EC 2.2.7.25) from Escherichia coli is presented. Initial velocity studies demonstrate that the mechanism is sequential and that high concentrations of tRNA give rise to substrate inhibition which is noncompetitive with respect to ATP. In addition, the substrate inhibition is more pronounced in the presence of pyrophosphate, which suggests the formation of an inhibitory enzyme-pyrophosphate-tRNA complex. Noncompetitive product inhibition is observed between all possible pairs of substrates and products. ADP and alpha,beta-methylene adenosine triphosphate are competitive dead end inhibitors of ATP, while the latter is a noncompetitive dead end inhibitor of the tRNA substrate. A nonrapid equilibrium random mechanism is proposed which is consistent with these data and offers an explanation for the noncompetitive substrate inhibition by tRNA.", "contents": "Kinetic mechanism of tRNA nucleotidyltransferase from Escherichia coli. A kinetic analysis of the incorporation of AMP into tRNA lacking the 3'-terminal residue by tRNA nucleotidyltransferase (EC 2.2.7.25) from Escherichia coli is presented. Initial velocity studies demonstrate that the mechanism is sequential and that high concentrations of tRNA give rise to substrate inhibition which is noncompetitive with respect to ATP. In addition, the substrate inhibition is more pronounced in the presence of pyrophosphate, which suggests the formation of an inhibitory enzyme-pyrophosphate-tRNA complex. Noncompetitive product inhibition is observed between all possible pairs of substrates and products. ADP and alpha,beta-methylene adenosine triphosphate are competitive dead end inhibitors of ATP, while the latter is a noncompetitive dead end inhibitor of the tRNA substrate. A nonrapid equilibrium random mechanism is proposed which is consistent with these data and offers an explanation for the noncompetitive substrate inhibition by tRNA."}
{"id": "PMID:18469", "title": "Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia.", "content": "Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography. The molecular weight was estimated by glycerol gradient centrifugation to be 50,000. This enzyme had an optimal activity at pH 7.1 and required a divalent cation in order to catalyze the reaction. Mg2+ and Mn2+ were found to be the preferential divalent cations. The activation energy was estimated to be 19.1 kcal/mol at pH 7.2. Initial velocity study suggested that the reaction followed a sequential mechanism. Mg2+ ATP had a Km of 0.25 mM and dTMP had a Km of 40 micrometer. The enzyme was unstable even at 4 degrees. In the presence of ATP or dTMP the enzyme maintained its activity. Purine triphosphate nucleosides were found to be better phosphate donors than the pyrimidine triphosphate nucleosides. ATP and dATP had a lower Km and a higher Vmax than GTP and dGTP. dTMP was the only preferred phosphate receptor among all the monophosphate nucleotides tested dTTP and IdUTP competed with both substrates and inhibited the reaction with a Ki of 0.75 mM and 1.1 mM, respectively.", "contents": "Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. Thymidylate kinase derived from the blast cells of human chronic myelocytic leukemia was purified 2186-fold to near homogeneity by means of alcohol precipitation, alumina-Cgamma gel fractionation, calcium phosphate gel fraction, ultrafiltration, and affinity column chromatography. The molecular weight was estimated by glycerol gradient centrifugation to be 50,000. This enzyme had an optimal activity at pH 7.1 and required a divalent cation in order to catalyze the reaction. Mg2+ and Mn2+ were found to be the preferential divalent cations. The activation energy was estimated to be 19.1 kcal/mol at pH 7.2. Initial velocity study suggested that the reaction followed a sequential mechanism. Mg2+ ATP had a Km of 0.25 mM and dTMP had a Km of 40 micrometer. The enzyme was unstable even at 4 degrees. In the presence of ATP or dTMP the enzyme maintained its activity. Purine triphosphate nucleosides were found to be better phosphate donors than the pyrimidine triphosphate nucleosides. ATP and dATP had a lower Km and a higher Vmax than GTP and dGTP. dTMP was the only preferred phosphate receptor among all the monophosphate nucleotides tested dTTP and IdUTP competed with both substrates and inhibited the reaction with a Ki of 0.75 mM and 1.1 mM, respectively."}
{"id": "PMID:18471", "title": "Partial purification of 6-(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate synthetase from chicken liver.", "content": "An enzyme that catalyzes the formation of 6-(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate (D-erythrodihydroneopterin triphosphate) and formic acid from GTP has been purified about 3700-fold from homogenates of chicken liver. The molecular weight of the enzyme, D-erythrodihydroneopterin triphosphate synthetase (GTP cyclohydrolase), has been estimated to be 125,000 by gel filtration on Ultrogel AcA-34. The enzyme functions optimally between pH 8.0 and 9.2 and is considerably heat-stable. No cofactors or metal ions have been demonstrated to be required for activity; however, the reaction is strongly inhibited by Cu2+ and Hg2+. GTP is the most efficient substrate, with GDP being 1/17 as active and guanosine, GMP, and ATP being inactive. The Km for GTP has been found to be 14 micrometer. Although the overall reaction catalyzed by D-erythrodihydroneopterin triphosphate synthetase from chicken liver is identical with that from Escherichia coli GTP cyclohydrolase, immunological studies show no apparent homology between the two enzymes.", "contents": "Partial purification of 6-(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate synthetase from chicken liver. An enzyme that catalyzes the formation of 6-(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihydropterin triphosphate (D-erythrodihydroneopterin triphosphate) and formic acid from GTP has been purified about 3700-fold from homogenates of chicken liver. The molecular weight of the enzyme, D-erythrodihydroneopterin triphosphate synthetase (GTP cyclohydrolase), has been estimated to be 125,000 by gel filtration on Ultrogel AcA-34. The enzyme functions optimally between pH 8.0 and 9.2 and is considerably heat-stable. No cofactors or metal ions have been demonstrated to be required for activity; however, the reaction is strongly inhibited by Cu2+ and Hg2+. GTP is the most efficient substrate, with GDP being 1/17 as active and guanosine, GMP, and ATP being inactive. The Km for GTP has been found to be 14 micrometer. Although the overall reaction catalyzed by D-erythrodihydroneopterin triphosphate synthetase from chicken liver is identical with that from Escherichia coli GTP cyclohydrolase, immunological studies show no apparent homology between the two enzymes."}
{"id": "PMID:18475", "title": "Selective de novo synthesis of tyrosine hydroxylase in organ cultures of rat superior cervical ganglia after in vivo administration of nerve growth factor.", "content": "Tyrosine hydroxylase is synthesized de novo in rat superior cervical ganglia in organ culture. The differential rate of synthesis is not increased significantly by the addition of nerve growth factor to the culture. Prior administration of nerve growth factor in vivo, however, leads to an augmented synthesis of tyrosine hydroxylase in ganglia subsequently cultured in vitro. The differential rate of tyrosine hydroxylase synthesis was increased by a factor of between 3 and 4. Increases in the differential rate of synthesis were detected within 6 h; the rate reached a maximum 24 to 36 h after a single injection of nerve growth factor. Administration of actinomycin D or of nerve growth factor antibody in vivo prevented the nerve growth factor-induced increase in the differential rate of tyrosine hydroxylase synthesis in vitro. However, the increase in the synthetic rate of tyrosine hydroxylase was not prevented by the addition of actinomycin D to the culture.", "contents": "Selective de novo synthesis of tyrosine hydroxylase in organ cultures of rat superior cervical ganglia after in vivo administration of nerve growth factor. Tyrosine hydroxylase is synthesized de novo in rat superior cervical ganglia in organ culture. The differential rate of synthesis is not increased significantly by the addition of nerve growth factor to the culture. Prior administration of nerve growth factor in vivo, however, leads to an augmented synthesis of tyrosine hydroxylase in ganglia subsequently cultured in vitro. The differential rate of tyrosine hydroxylase synthesis was increased by a factor of between 3 and 4. Increases in the differential rate of synthesis were detected within 6 h; the rate reached a maximum 24 to 36 h after a single injection of nerve growth factor. Administration of actinomycin D or of nerve growth factor antibody in vivo prevented the nerve growth factor-induced increase in the differential rate of tyrosine hydroxylase synthesis in vitro. However, the increase in the synthetic rate of tyrosine hydroxylase was not prevented by the addition of actinomycin D to the culture."}
{"id": "PMID:18477", "title": "Solubilization and partial purification of heme oxygenase from rat liver.", "content": "Hepatic microsomal heme oxygenase was solubilized, partially purified, and characterized from Co2+-treated rats. The enzyme on sodium dodecyl sulfate-polyacrylamide gel electrophoresis exhibited a minimum molecular weight of greater than or equal to 68,000. The solubilized enzyme was totally devoid of contamination with cytochrome P-450 or b5. The requirement for reduced pyridine nucleotides was absolute, and ascorbate could not support heme oxidative activity. However, both TPNH and DPNH could serve as electron donors, with TPNH being more effective. The presence of an appropriate flavoprotein reductase was essential for heme oxidation. The enzyme had an apparent Km of 40 micrometer, a pH optimum of 7.5, and lost substantial activity upon freezing and thawing. Methemoglobin was 30% as effective a substrate for the enzyme as was heme. Free porphyrins could not serve as substrates for the enzyme. The activity of the enzyme was inhibited by HgCl2, p-chloromercuribenzoate, iodoacetamide, mercaptoethanol, and dithiothrietol indicating that free -SH group(s) is necessary for enzyme activity.", "contents": "Solubilization and partial purification of heme oxygenase from rat liver. Hepatic microsomal heme oxygenase was solubilized, partially purified, and characterized from Co2+-treated rats. The enzyme on sodium dodecyl sulfate-polyacrylamide gel electrophoresis exhibited a minimum molecular weight of greater than or equal to 68,000. The solubilized enzyme was totally devoid of contamination with cytochrome P-450 or b5. The requirement for reduced pyridine nucleotides was absolute, and ascorbate could not support heme oxidative activity. However, both TPNH and DPNH could serve as electron donors, with TPNH being more effective. The presence of an appropriate flavoprotein reductase was essential for heme oxidation. The enzyme had an apparent Km of 40 micrometer, a pH optimum of 7.5, and lost substantial activity upon freezing and thawing. Methemoglobin was 30% as effective a substrate for the enzyme as was heme. Free porphyrins could not serve as substrates for the enzyme. The activity of the enzyme was inhibited by HgCl2, p-chloromercuribenzoate, iodoacetamide, mercaptoethanol, and dithiothrietol indicating that free -SH group(s) is necessary for enzyme activity."}
{"id": "PMID:18479", "title": "Biochemical and cytochemical evidence for ATPase activity in basal bodies isolated from oviduct.", "content": "Biochemical and cytochemical techniques were used to determine whether oviduct basal bodies have ATPase activity. All studies were carried out on basal bodies isolated and purified from the chicken oviduct. These preparations contained structurally intact basal bodies with basal feet, rootlet, and alar sheet accessory structures. Whereas the specific activity of the basal body ATPase in 2 mM Ca++ or 2 mM Mg++, 1 mM ATP, pH 8.0, averaged 0.04 mumol Pi/min per mg protein, higher concentrations of either cation inhibited the enzyme activity. Furthermore, the pH optimum for this reaction was pH 8.5. In comparison, the ATPase activity in cilia purified and measured under conditions identical to those for determining the basal body ATPase activity averaged 0.07 mumol Pi/min per mg protein. However, the activity increased at higher concentrations of divalent cation, and the pH optimum was pH 10.0. By cytochemical procedures for localizing ATPase activity, ATP-dependent reaction product in isolated basal bodies was found to be confined to: (a) the cross-striations of the rootlet; (b) the outer portion of the basal foot; (c) the alar sheets; and (d) the triplet microtubules. It is concluded that basal bodiesve an intrinsic ATPase activity that, by a variety of criteria, can be distinguished from the ATPase activity found in cilia.", "contents": "Biochemical and cytochemical evidence for ATPase activity in basal bodies isolated from oviduct. Biochemical and cytochemical techniques were used to determine whether oviduct basal bodies have ATPase activity. All studies were carried out on basal bodies isolated and purified from the chicken oviduct. These preparations contained structurally intact basal bodies with basal feet, rootlet, and alar sheet accessory structures. Whereas the specific activity of the basal body ATPase in 2 mM Ca++ or 2 mM Mg++, 1 mM ATP, pH 8.0, averaged 0.04 mumol Pi/min per mg protein, higher concentrations of either cation inhibited the enzyme activity. Furthermore, the pH optimum for this reaction was pH 8.5. In comparison, the ATPase activity in cilia purified and measured under conditions identical to those for determining the basal body ATPase activity averaged 0.07 mumol Pi/min per mg protein. However, the activity increased at higher concentrations of divalent cation, and the pH optimum was pH 10.0. By cytochemical procedures for localizing ATPase activity, ATP-dependent reaction product in isolated basal bodies was found to be confined to: (a) the cross-striations of the rootlet; (b) the outer portion of the basal foot; (c) the alar sheets; and (d) the triplet microtubules. It is concluded that basal bodiesve an intrinsic ATPase activity that, by a variety of criteria, can be distinguished from the ATPase activity found in cilia."}
{"id": "PMID:18480", "title": "The activity of the pneumococcal autolytic system and the fate of the bacterium during ingestion by rabbit polymorphonuclear leukocytes.", "content": "The extent to which autolytic microbial enzymes are involved in the fate of microorganisms ingested by phagocytes has not been determined. It is known, however, that activation of degradative enzymes occurs during certain microbicidal events. We examined the possible role of the pneumococcal autolytic enzyme (an N-acetylmuramyl-L-alanine amidase) in the loss of viability and degradation of pneumococci during phagocytosis by rabbit polymorphonuclear leukocytes. Three bacterial systems were compared: (a) wild type pneumococci with an active autolytic system; (b) wild type bacteria grown under conditions that block the endogenous autolytic activity and (c) a mutant strain defective in the major autolytic enzyme of this bacterium. No differences could be detected between the autolysis-positive and negative bacteria in the rate of killing and in the fate of macromolecular cell constituents during ingestion by rabbit peritoneal polymorphonuclear leukocytes.", "contents": "The activity of the pneumococcal autolytic system and the fate of the bacterium during ingestion by rabbit polymorphonuclear leukocytes. The extent to which autolytic microbial enzymes are involved in the fate of microorganisms ingested by phagocytes has not been determined. It is known, however, that activation of degradative enzymes occurs during certain microbicidal events. We examined the possible role of the pneumococcal autolytic enzyme (an N-acetylmuramyl-L-alanine amidase) in the loss of viability and degradation of pneumococci during phagocytosis by rabbit polymorphonuclear leukocytes. Three bacterial systems were compared: (a) wild type pneumococci with an active autolytic system; (b) wild type bacteria grown under conditions that block the endogenous autolytic activity and (c) a mutant strain defective in the major autolytic enzyme of this bacterium. No differences could be detected between the autolysis-positive and negative bacteria in the rate of killing and in the fate of macromolecular cell constituents during ingestion by rabbit peritoneal polymorphonuclear leukocytes."}
{"id": "PMID:18478", "title": "Hypopotassemia following open heart surgery by cardio-pulmonary bypass.", "content": "1. In this study where potassium concentration of perfusate of heart-lung machine was made high and no potassium was given until two hours after by-pass, the fall of plasma potassium level due to heart-lung bypass occurred in two stages, namely one hour of complete bypass and two hours after the end of bypass. 2. Regarding to the decrease of these plasma potassium level, increase of potassium excretion into urine and the movement of potassium from extracellular fluid into cells are presumed to be causes. Their genesis was discussed. 3. To prevent hypopotassemia following bypass, it is recommended to add KCl in the perfusate of heart-lung machine and to give intravenous drip of KCl immediately after bypass.", "contents": "Hypopotassemia following open heart surgery by cardio-pulmonary bypass. 1. In this study where potassium concentration of perfusate of heart-lung machine was made high and no potassium was given until two hours after by-pass, the fall of plasma potassium level due to heart-lung bypass occurred in two stages, namely one hour of complete bypass and two hours after the end of bypass. 2. Regarding to the decrease of these plasma potassium level, increase of potassium excretion into urine and the movement of potassium from extracellular fluid into cells are presumed to be causes. Their genesis was discussed. 3. To prevent hypopotassemia following bypass, it is recommended to add KCl in the perfusate of heart-lung machine and to give intravenous drip of KCl immediately after bypass."}
{"id": "PMID:18481", "title": "Renal enzymes in kidney cells selected by D-valine medium.", "content": "The ability of D-valine medium to inhibit fibroblasts in cultures derived from kidneys of various mammals has enabled the selective proliferation of epithlial cells in the absence of fibroblast overgrowth. Studies of these selected epithelial cells have demonstrated the presence of D-amino acid oxidase, carbonic anhydrase, high levels of alkaline phosphatase and the renal specific pattern of lactate dehydrogenase. The presence of these renal enzymes suggests that the selected epithelial cells are of renal tubular origin and indicates that these differentiated functions are retained in cultured cells.", "contents": "Renal enzymes in kidney cells selected by D-valine medium. The ability of D-valine medium to inhibit fibroblasts in cultures derived from kidneys of various mammals has enabled the selective proliferation of epithlial cells in the absence of fibroblast overgrowth. Studies of these selected epithelial cells have demonstrated the presence of D-amino acid oxidase, carbonic anhydrase, high levels of alkaline phosphatase and the renal specific pattern of lactate dehydrogenase. The presence of these renal enzymes suggests that the selected epithelial cells are of renal tubular origin and indicates that these differentiated functions are retained in cultured cells."}
{"id": "PMID:18483", "title": "Interaction of local anesthetics with the transport system of glucose in human erythrocytes.", "content": "Local anesthetics inhibit the exhange transport of glucose in human erythroytes. All compounds tested showed a competitive inhibition except lidocaine and baycaine causing a non-competitive one. Moreover the transport system can bind two inhibitor molecules to one transport site as described for tetracaine and oxybuprocaine.", "contents": "Interaction of local anesthetics with the transport system of glucose in human erythrocytes. Local anesthetics inhibit the exhange transport of glucose in human erythroytes. All compounds tested showed a competitive inhibition except lidocaine and baycaine causing a non-competitive one. Moreover the transport system can bind two inhibitor molecules to one transport site as described for tetracaine and oxybuprocaine."}
{"id": "PMID:18484", "title": "Reversion in expression of hypoxanthine-guanine phosphoribosyltransferase in 6-thioguanine resistant neuroblastoma: evidence for reduced enzyme levels associated with unaltered catalytic activity.", "content": "Five clones of mouse neuroblastoma cells able to grow in hypoxanthine-aminopterin-thymidine containing medium were isolated from a hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8; IMP: pyrophosphate phosphoribosyltransferase) deficient cell line. These hypoxanthine-aminopterin-thymidine resistant revertant clone had 45-55% of wild-type cell HGPRT activity. Kinetic studies indicated that the HGPRT in revertant clones had a reduced maximal velocity as compared to wild type cells based on cell protein. Apparent Km values of HGPRT for hypoxanthine and 5-phosphoribosyl-1-pyrophosphate were similar in wild-type and revertant cells. Heat inactivation studies demonstrated a similar heat lability for HGPRT in revertant and wild-type cells. An antibody fraction prepared from serum of rabbits immunized with HGPRT partially purified from mouse liver was used to measure the amount of cross-reacting material in normal and revertant clones. The revertant clones had one-half the amounth of cross-reacting material present in wild-type cells, based on a given amount of cell protein. These data indicate that the revertant cells may contain fewer HGPRT molecules with unaltered catalytic activity.", "contents": "Reversion in expression of hypoxanthine-guanine phosphoribosyltransferase in 6-thioguanine resistant neuroblastoma: evidence for reduced enzyme levels associated with unaltered catalytic activity. Five clones of mouse neuroblastoma cells able to grow in hypoxanthine-aminopterin-thymidine containing medium were isolated from a hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8; IMP: pyrophosphate phosphoribosyltransferase) deficient cell line. These hypoxanthine-aminopterin-thymidine resistant revertant clone had 45-55% of wild-type cell HGPRT activity. Kinetic studies indicated that the HGPRT in revertant clones had a reduced maximal velocity as compared to wild type cells based on cell protein. Apparent Km values of HGPRT for hypoxanthine and 5-phosphoribosyl-1-pyrophosphate were similar in wild-type and revertant cells. Heat inactivation studies demonstrated a similar heat lability for HGPRT in revertant and wild-type cells. An antibody fraction prepared from serum of rabbits immunized with HGPRT partially purified from mouse liver was used to measure the amount of cross-reacting material in normal and revertant clones. The revertant clones had one-half the amounth of cross-reacting material present in wild-type cells, based on a given amount of cell protein. These data indicate that the revertant cells may contain fewer HGPRT molecules with unaltered catalytic activity."}
{"id": "PMID:18486", "title": "Analysis of medazepam, diazepam, and metabolites in plasma by gas-liquid chromatography with electrolytic conductivity detection.", "content": "An improved electrolytic conductivity detector allowed the gas-liquid chromatographic analysis of medazepam, diazepam, and major metabolites in 2 ml plasma at concentrations of 20 microgram/l. The detector had a sensitivity limit of less than 1 ng (or 100 pg nitrogen) when operated in the nitrogen-selective mode and a nitrogen/carbon elemental selectivity ratio of greater than 100,000 compared to octadecane and cholesterol. Detector response when operated in various element-selective chemical modes was investigated, and its application to the analysis of the title compounds was compared to electron capture and flame ionization detection systems.", "contents": "Analysis of medazepam, diazepam, and metabolites in plasma by gas-liquid chromatography with electrolytic conductivity detection. An improved electrolytic conductivity detector allowed the gas-liquid chromatographic analysis of medazepam, diazepam, and major metabolites in 2 ml plasma at concentrations of 20 microgram/l. The detector had a sensitivity limit of less than 1 ng (or 100 pg nitrogen) when operated in the nitrogen-selective mode and a nitrogen/carbon elemental selectivity ratio of greater than 100,000 compared to octadecane and cholesterol. Detector response when operated in various element-selective chemical modes was investigated, and its application to the analysis of the title compounds was compared to electron capture and flame ionization detection systems."}
{"id": "PMID:18487", "title": "Use of an amino-silica column for the high-performance liquid chromatographic analysis of synthetic oligodeoxy-nucleotides.", "content": "The use of an amino-silica column in the chromatographic analysis of synthetic oligodeoxyribonucleotides and their derivatives from different stages of oligonucleotide synthesis has been investigated. By eluting with 0.10 M potassium phosphate solution of pH 3.30, the nucleotide composition of oligonucleotides can be established within 15 min. In a linear gradient of phosphate buffer (0.10-0.75 M) at neutral pH, the separation of oligonucleotides by length and in an acidic medium pH 3.30-4.30) by composition is possible; the oligonucleotides may be in the free form or modified by the various protecting groups used in synthetic oligonucleotide chemistry. The analysis of some reaction mixtures from different stages of oligonucleotide synthesis and of a number of synthetic oligodeoxyribonucleotides and their derivatives has been performed.", "contents": "Use of an amino-silica column for the high-performance liquid chromatographic analysis of synthetic oligodeoxy-nucleotides. The use of an amino-silica column in the chromatographic analysis of synthetic oligodeoxyribonucleotides and their derivatives from different stages of oligonucleotide synthesis has been investigated. By eluting with 0.10 M potassium phosphate solution of pH 3.30, the nucleotide composition of oligonucleotides can be established within 15 min. In a linear gradient of phosphate buffer (0.10-0.75 M) at neutral pH, the separation of oligonucleotides by length and in an acidic medium pH 3.30-4.30) by composition is possible; the oligonucleotides may be in the free form or modified by the various protecting groups used in synthetic oligonucleotide chemistry. The analysis of some reaction mixtures from different stages of oligonucleotide synthesis and of a number of synthetic oligodeoxyribonucleotides and their derivatives has been performed."}
{"id": "PMID:18488", "title": "Cimetidine, an H2-antihistamine, stimulates prolactin secretion in man.", "content": "Intravenous administration of cimetidine, a histamine (H2) receptor antagonist, provoked an immediate 2 to 3-fold rise in serum prolactin concentrations in 8 normal men; serum thyrotropin, growth hormone, thyroxine, and triiodothyronine were not significantly affected. Diphenhydramine, an H1-antagonist, was without effect on any of the hormones measured. The results suggest that histamine may have an important function in the regulation of prolactin secretion in man.", "contents": "Cimetidine, an H2-antihistamine, stimulates prolactin secretion in man. Intravenous administration of cimetidine, a histamine (H2) receptor antagonist, provoked an immediate 2 to 3-fold rise in serum prolactin concentrations in 8 normal men; serum thyrotropin, growth hormone, thyroxine, and triiodothyronine were not significantly affected. Diphenhydramine, an H1-antagonist, was without effect on any of the hormones measured. The results suggest that histamine may have an important function in the regulation of prolactin secretion in man."}
{"id": "PMID:18489", "title": "Value of sputum culture in diagnosis of pneumococcal pneumonia.", "content": "In our laboratory, culture of sputum was extremely useful in diagnosing the etiology of pneumococcal pneumonia. Of 31 consecutive patients with bacteremic pneumococcal pneumonia, 29 (94%) had Streptococcus pneumoniae cultured from sputum. Recovery of pneumococci in culture was enhanced by anaerobic incubation as well as by a plate bile test and an optochin disk on a primary blood agar plate.", "contents": "Value of sputum culture in diagnosis of pneumococcal pneumonia. In our laboratory, culture of sputum was extremely useful in diagnosing the etiology of pneumococcal pneumonia. Of 31 consecutive patients with bacteremic pneumococcal pneumonia, 29 (94%) had Streptococcus pneumoniae cultured from sputum. Recovery of pneumococci in culture was enhanced by anaerobic incubation as well as by a plate bile test and an optochin disk on a primary blood agar plate."}
{"id": "PMID:18490", "title": "Cytochemical reactions of normal and neoplastic lymphocytes.", "content": "Rosetting and non-rosetting lymphocytes collected from normal individuals were stained for the presence of beta-glucuronidase, periodic-acid Schiff activity, gamma glutamyl transpeptidase, acid phosphatase, and alpha-naphthyl butyrate esterase. Lymphocytes which formed rosettes with sheep erythrocytes and non-rosette forming lymphocytes contained cytochemical reaction products for all five stains. Beta-glucuronidase (P less than 0-02) and acid phosphatase (P less than 0-01) were more frequently found in rosette forming lymphocytes. However, non-rosetting cells were more frequently periodic-acid Schiff positive (P less than 0-001). Gamma-glutamyl transpeptidase and alpha-naphthyl butyrate esterase were present equally in rosette and non-rosette forming lymphocytes. In addition, 33 non-Hodgkin's lymphomas were studied for cell surface markers and cytochemical reactions. In 17 of 19 B cell lymphomas, there was a paucity of lymphocytes containing beta-glucuronidase. However, in three of four T cell proliferations, there were numerous lymphoid cells positive for beta-glucuronidase. The periodic-acid Schiff and acid phosphatase reactions varied greatly within B, T, and null cell lymphomas and thus were of little diagnostic value in determining the cell of origin of these neoplastic lymphoid cells.", "contents": "Cytochemical reactions of normal and neoplastic lymphocytes. Rosetting and non-rosetting lymphocytes collected from normal individuals were stained for the presence of beta-glucuronidase, periodic-acid Schiff activity, gamma glutamyl transpeptidase, acid phosphatase, and alpha-naphthyl butyrate esterase. Lymphocytes which formed rosettes with sheep erythrocytes and non-rosette forming lymphocytes contained cytochemical reaction products for all five stains. Beta-glucuronidase (P less than 0-02) and acid phosphatase (P less than 0-01) were more frequently found in rosette forming lymphocytes. However, non-rosetting cells were more frequently periodic-acid Schiff positive (P less than 0-001). Gamma-glutamyl transpeptidase and alpha-naphthyl butyrate esterase were present equally in rosette and non-rosette forming lymphocytes. In addition, 33 non-Hodgkin's lymphomas were studied for cell surface markers and cytochemical reactions. In 17 of 19 B cell lymphomas, there was a paucity of lymphocytes containing beta-glucuronidase. However, in three of four T cell proliferations, there were numerous lymphoid cells positive for beta-glucuronidase. The periodic-acid Schiff and acid phosphatase reactions varied greatly within B, T, and null cell lymphomas and thus were of little diagnostic value in determining the cell of origin of these neoplastic lymphoid cells."}
{"id": "PMID:18491", "title": "The effect of a new benzodiazepine on the polygraphically monitored sleep of normal volunteers.", "content": "All-night sleep was polygraphically monitored from ten normal volunteers who took placebo and three dosage levels of a new benzodiazepine hypnotic, SCH 16134, in a double-blind, crossover design. All dosages of the drug decreased the time to fall asleep, and the two highest dosages also decreased interspersed wakefulness. REM sleep was suppressed, but slow-wave sleep was not affected in this experiment. The subjective quality of sleep was improved by the new hypnotic. One subject reported that he felt lethargic the day after the largest dose.", "contents": "The effect of a new benzodiazepine on the polygraphically monitored sleep of normal volunteers. All-night sleep was polygraphically monitored from ten normal volunteers who took placebo and three dosage levels of a new benzodiazepine hypnotic, SCH 16134, in a double-blind, crossover design. All dosages of the drug decreased the time to fall asleep, and the two highest dosages also decreased interspersed wakefulness. REM sleep was suppressed, but slow-wave sleep was not affected in this experiment. The subjective quality of sleep was improved by the new hypnotic. One subject reported that he felt lethargic the day after the largest dose."}
{"id": "PMID:18492", "title": "Multiclinic double-blind comparison of triazolam and flurazepam for seven nights in outpatients with insomnia.", "content": "In this two-clinic seven-day double-blind study, 0.5 mg triazolam (Halcion) was compared to flurazepam (Dalmane) in the treatment of insomnia. Two clinical investigators completed 118 outpatients, 61 on triazolam and 57 on flurazepam. Five patients, four on triazolam and one on flurazepam, discontinued because of side effects; and three patients, one on triazolam and two on flurazepam, discontinued because of ineffectiveness of the medication. Analysis of pooled data for the 110 evaluable patients showed that 0.5 mg triazolam was significantly better than 30 mg flurazepam on the following parameters: (1) how much the medication helped the patients sleep, (2) onset of sleep, (3) duration of sleep, (4) evaluation of duration of sleep, and (5) feeling of restfulness in the morning. The trend for all other parameters favored triazolam treatment, but the values did not reach statistical significance. Side effects were similar in both groups, with drowsiness being reported most frequently. No change in efficacy indicating tolerance development during the seven days of drug administration was observed in either group.", "contents": "Multiclinic double-blind comparison of triazolam and flurazepam for seven nights in outpatients with insomnia. In this two-clinic seven-day double-blind study, 0.5 mg triazolam (Halcion) was compared to flurazepam (Dalmane) in the treatment of insomnia. Two clinical investigators completed 118 outpatients, 61 on triazolam and 57 on flurazepam. Five patients, four on triazolam and one on flurazepam, discontinued because of side effects; and three patients, one on triazolam and two on flurazepam, discontinued because of ineffectiveness of the medication. Analysis of pooled data for the 110 evaluable patients showed that 0.5 mg triazolam was significantly better than 30 mg flurazepam on the following parameters: (1) how much the medication helped the patients sleep, (2) onset of sleep, (3) duration of sleep, (4) evaluation of duration of sleep, and (5) feeling of restfulness in the morning. The trend for all other parameters favored triazolam treatment, but the values did not reach statistical significance. Side effects were similar in both groups, with drowsiness being reported most frequently. No change in efficacy indicating tolerance development during the seven days of drug administration was observed in either group."}
{"id": "PMID:18493", "title": "Effect of a new benzodiazepine derivate, clobazam, in anxious patients with gastrointestinal disorders.", "content": "Thirty-four anxious patients with gastrointestinal disorders were studied in order to evaluate the effectiveness of a new 1,5-benzodiazepine antianxiety agent (HR 376). The disorders were classified as organic or functional according to the presence or absence of radiologic signs of ulcer. Dietetic measures, gastric antacids, anticholinergic agents, and antianxiety treatment were applied for six weeks. Anxiolytic treatment consisted of 30 mg/day clobazam (HR 376) or 15 mg/day diazepam, given in a randomized, double-blind manner. Clinical follow-up was performed with the PEN Personality Inventory (PEN), Taylor Manifest Anxiety Scale (TMAS), Hamilton Anxiety Scale (HAS), and Wittenborn Psychiatric Rating Scales (WPRS). The score of the psychoticism dimension of the PEN inventory was significantly higher in organic than in functional patients. Significant differences occurred in the reduction of the rating scores of HAS and WPRS before/after treatment in the clobazam and diazepam groups. This would express a modification of state anxiety. The TMAS, which evaluates trait anxiety, disclosed statistically significant improvement in the clobazam group. This group showed an early reduction of the HAS and TMAS scores, which would suggest an early onset of action.", "contents": "Effect of a new benzodiazepine derivate, clobazam, in anxious patients with gastrointestinal disorders. Thirty-four anxious patients with gastrointestinal disorders were studied in order to evaluate the effectiveness of a new 1,5-benzodiazepine antianxiety agent (HR 376). The disorders were classified as organic or functional according to the presence or absence of radiologic signs of ulcer. Dietetic measures, gastric antacids, anticholinergic agents, and antianxiety treatment were applied for six weeks. Anxiolytic treatment consisted of 30 mg/day clobazam (HR 376) or 15 mg/day diazepam, given in a randomized, double-blind manner. Clinical follow-up was performed with the PEN Personality Inventory (PEN), Taylor Manifest Anxiety Scale (TMAS), Hamilton Anxiety Scale (HAS), and Wittenborn Psychiatric Rating Scales (WPRS). The score of the psychoticism dimension of the PEN inventory was significantly higher in organic than in functional patients. Significant differences occurred in the reduction of the rating scores of HAS and WPRS before/after treatment in the clobazam and diazepam groups. This would express a modification of state anxiety. The TMAS, which evaluates trait anxiety, disclosed statistically significant improvement in the clobazam group. This group showed an early reduction of the HAS and TMAS scores, which would suggest an early onset of action."}
{"id": "PMID:18494", "title": "Effect of electrical stimulation of the autonomic nerves on the levels and synthesis of cyclic nucleotides in the rat salivary glands: relationship to enhanced growth.", "content": "Electrical stimulation of either the parasympathetic or the sympathetic nerve supply to the parotid and submaxillary glands increases the intracellular level of cyclic GMP and the rate of DNA synthesis and cell division while only sympathetic stimulation raises cyclic AMP levels. The periods of electrical stimulation inducing hyperplasia also raise the cyclic GMP concentration but there is no similar correlation with changes in cyclic AMP levels. However, the extent of hyperplasia induced by parasympathetic and sympathetic stimulation is not directly related to the size of the increase in cyclic GMP concentration that these treatments produce. Changes in cyclic AMP levels are reflected in altered in vitro adenylate cyclase activity. This activity is raised after 2 min sympathetic stimulation and markedly decreased with 30 min sympathetic or parasympathetic stimulation. Guanylate cyclase activity shows no such changes with nerve stimulation.", "contents": "Effect of electrical stimulation of the autonomic nerves on the levels and synthesis of cyclic nucleotides in the rat salivary glands: relationship to enhanced growth. Electrical stimulation of either the parasympathetic or the sympathetic nerve supply to the parotid and submaxillary glands increases the intracellular level of cyclic GMP and the rate of DNA synthesis and cell division while only sympathetic stimulation raises cyclic AMP levels. The periods of electrical stimulation inducing hyperplasia also raise the cyclic GMP concentration but there is no similar correlation with changes in cyclic AMP levels. However, the extent of hyperplasia induced by parasympathetic and sympathetic stimulation is not directly related to the size of the increase in cyclic GMP concentration that these treatments produce. Changes in cyclic AMP levels are reflected in altered in vitro adenylate cyclase activity. This activity is raised after 2 min sympathetic stimulation and markedly decreased with 30 min sympathetic or parasympathetic stimulation. Guanylate cyclase activity shows no such changes with nerve stimulation."}
{"id": "PMID:18496", "title": "Fetal and maternal plasma electrolytes, blood gases, and pH in dairy cows during late gestation.", "content": "Sodium, potassium, and chloride were determined in fetal and maternal plasma of six cows between 208 and 269 days of gestation. Blood pH and partial pressures of oxygen and carbon dioxide also were measured in samples collected from the jugular vein of the cow and the caudal aorta and vena cava of the fetus. Concentration of chloride in fetal plasma was generally lower than the corresponding maternal value, and fetal potassium was greater than maternal. Potassium of fetal plasma increased towards term. Sodium concentrations were not significantly different between fetal and maternal plasms. Once fetal and maternal pH and blood gas tensions had stabilized after surgery, there was little change until shortly before delivery. In the last 24 h before calving maternal partial pressure of oxygen was high and fetal blood pH was low.", "contents": "Fetal and maternal plasma electrolytes, blood gases, and pH in dairy cows during late gestation. Sodium, potassium, and chloride were determined in fetal and maternal plasma of six cows between 208 and 269 days of gestation. Blood pH and partial pressures of oxygen and carbon dioxide also were measured in samples collected from the jugular vein of the cow and the caudal aorta and vena cava of the fetus. Concentration of chloride in fetal plasma was generally lower than the corresponding maternal value, and fetal potassium was greater than maternal. Potassium of fetal plasma increased towards term. Sodium concentrations were not significantly different between fetal and maternal plasms. Once fetal and maternal pH and blood gas tensions had stabilized after surgery, there was little change until shortly before delivery. In the last 24 h before calving maternal partial pressure of oxygen was high and fetal blood pH was low."}
{"id": "PMID:18540", "title": "Biochemical and histocytochemical studies on response of ammonia-producing enzymes for nh4cl-induced acidosis.", "content": "NH4Cl-induced acidosis in rats resulted in renal enlargement and increase in activities of phosphate-dependent glutaminase and glutamic dehydrogenase. The renal enlargement was associated with protein synthesis but not deoxyribonucleic acid synthesis. In control rats histochemical activity of glutamic dehydrogenase was seen dominantly in the proximal straight tubule. In acidotic rats high activity was noted in the proximal convoluted tubule as well as in the proximal straight tubule. By electron microscopy reaction product was in mitochondria. The results suggest that urine ammonia is produced in mitochondria of epithelial cells in the proximal straight tubule in both normal and acidotic rats. Increased enzyme activity in acidotic rats is largely associated with epithelial cells of the proximal convoluted tubule.", "contents": "Biochemical and histocytochemical studies on response of ammonia-producing enzymes for nh4cl-induced acidosis. NH4Cl-induced acidosis in rats resulted in renal enlargement and increase in activities of phosphate-dependent glutaminase and glutamic dehydrogenase. The renal enlargement was associated with protein synthesis but not deoxyribonucleic acid synthesis. In control rats histochemical activity of glutamic dehydrogenase was seen dominantly in the proximal straight tubule. In acidotic rats high activity was noted in the proximal convoluted tubule as well as in the proximal straight tubule. By electron microscopy reaction product was in mitochondria. The results suggest that urine ammonia is produced in mitochondria of epithelial cells in the proximal straight tubule in both normal and acidotic rats. Increased enzyme activity in acidotic rats is largely associated with epithelial cells of the proximal convoluted tubule."}
{"id": "PMID:18541", "title": "Bunyavirus isolations from mosquitoes in the western Canadian Arctic.", "content": "Strains of California encephalitis virus (snowshoe hare subtype) were isolated from 8 of 475 pools comprising 23 747 unengorged female mosquitoes of five species collected at three of six locations throughout the Mackenzie Valley of the Northwest Territories, Canada, from latitudes 60 to 69 degrees N between 10 and 24 July 1976. Minimum field infection rates included 1:2734 for Aedes communis, 1:256 to 1:3662 for A. hexodontus and 1:911 to 1:1611 for A. punctor. Northway virus was also isolated from 1 of 3662 A. hexodontus mosquitoes collected at Inuvik (69 degrees N, 135 degrees W). Transmission of CE virus by A. communis infected by feeding on virus in defibrinated blood and incubation at 0, 13 and 23 degrees C for 13-20 days clearly demonstrates the importance of this species as a natural vector, and transmission of CE virus by Culiseta inornata after incubation at 0 and 13 degrees C following intrathoracic injection strengthens evidence of its role as a natural vector. Immunofluorescence was less reliable than imunoperoxidase for detection of CE viral antigen in mosquito salivary glands.", "contents": "Bunyavirus isolations from mosquitoes in the western Canadian Arctic. Strains of California encephalitis virus (snowshoe hare subtype) were isolated from 8 of 475 pools comprising 23 747 unengorged female mosquitoes of five species collected at three of six locations throughout the Mackenzie Valley of the Northwest Territories, Canada, from latitudes 60 to 69 degrees N between 10 and 24 July 1976. Minimum field infection rates included 1:2734 for Aedes communis, 1:256 to 1:3662 for A. hexodontus and 1:911 to 1:1611 for A. punctor. Northway virus was also isolated from 1 of 3662 A. hexodontus mosquitoes collected at Inuvik (69 degrees N, 135 degrees W). Transmission of CE virus by A. communis infected by feeding on virus in defibrinated blood and incubation at 0, 13 and 23 degrees C for 13-20 days clearly demonstrates the importance of this species as a natural vector, and transmission of CE virus by Culiseta inornata after incubation at 0 and 13 degrees C following intrathoracic injection strengthens evidence of its role as a natural vector. Immunofluorescence was less reliable than imunoperoxidase for detection of CE viral antigen in mosquito salivary glands."}
{"id": "PMID:18543", "title": "Regulation of cell-mediated cytotoxicity. III. Synergism of cortico-resistant with anti-thymocyte serum-resistant splenic T cells in the generation of cytotoxic lymphocytes in graft-vs-host reactions.", "content": "Lethally irradiated F1 hybrid mice were given an i.v. injection of parental strain spleen cells. Six days later, their spleen cells were used as the effector cells to measure the in vitro cell-mediated cytotoxicity (CMC) of the parental cells. The treatment of the donors with hydrocortisone resulted in a marked decrease of the capacity of their spleen cells to produce a CMC reaction, whereas the treatment with antithymocyte serum (ATS) resulted in an almost complete loss of such activity. The mixing of spleen cells from hydrocortisone-treated parental donors with the spleen cells from ATS-treated parental donors before injection resulted in a synergistic amplification of the cytotoxic response. The anti-Thy-1 serum treatment of either spleen cell population abolished the synergism completely. These results indicate that cortico-resistant T cells act as precursors of cytotoxic lymphocytes and that ATS-resistant T cells produce an amplification of their reaction.", "contents": "Regulation of cell-mediated cytotoxicity. III. Synergism of cortico-resistant with anti-thymocyte serum-resistant splenic T cells in the generation of cytotoxic lymphocytes in graft-vs-host reactions. Lethally irradiated F1 hybrid mice were given an i.v. injection of parental strain spleen cells. Six days later, their spleen cells were used as the effector cells to measure the in vitro cell-mediated cytotoxicity (CMC) of the parental cells. The treatment of the donors with hydrocortisone resulted in a marked decrease of the capacity of their spleen cells to produce a CMC reaction, whereas the treatment with antithymocyte serum (ATS) resulted in an almost complete loss of such activity. The mixing of spleen cells from hydrocortisone-treated parental donors with the spleen cells from ATS-treated parental donors before injection resulted in a synergistic amplification of the cytotoxic response. The anti-Thy-1 serum treatment of either spleen cell population abolished the synergism completely. These results indicate that cortico-resistant T cells act as precursors of cytotoxic lymphocytes and that ATS-resistant T cells produce an amplification of their reaction."}
{"id": "PMID:18546", "title": "Differential susceptibility of Escherichia coli and Proteus mirabilis to mouse urine and to urea.", "content": "The purpose of this investigation was to compare the antimicrobial properties of mouse urine and of urea against Escherichia coli and Proteus mirabilis. Nornal urine was found to inhibit the growth of E. coli and P. mirabilis, whereas urine from diuresing animals permitted multiplication of these bacteria. Addition of urea to urine from diuresing animals restored its bactericidal effect on P. mirabilis but not on E. coli. This bactericidal effect on P. mirabilis was dependent on the additive action of high content of urea and high pH and was prevented by the addition of urease inhibitor.", "contents": "Differential susceptibility of Escherichia coli and Proteus mirabilis to mouse urine and to urea. The purpose of this investigation was to compare the antimicrobial properties of mouse urine and of urea against Escherichia coli and Proteus mirabilis. Nornal urine was found to inhibit the growth of E. coli and P. mirabilis, whereas urine from diuresing animals permitted multiplication of these bacteria. Addition of urea to urine from diuresing animals restored its bactericidal effect on P. mirabilis but not on E. coli. This bactericidal effect on P. mirabilis was dependent on the additive action of high content of urea and high pH and was prevented by the addition of urease inhibitor."}
{"id": "PMID:18549", "title": "Alteration of structure and penetrability of the vitelline envelope after passage of eggs from coelom to oviduct in Xenopus laevis.", "content": "The vitelline envelope (VE) that surrounds an egg released from the ovary into the coelom of Xenopus laevis differs markedly, in structure and penetrability, from the VE surrounding an oviposited egg. In a coelomic egg, the filaments that form the VE are arranged in distinct fascicles or bundles. The exterior surface of the VE is irregular in contour and is permeated by channels. In an oviposited egg, the filaments are evenly dispersed and lack a fasciculated arrangement; the exterior surface is smooth and no channels are present. The fascicular arrangement of fibrils in the coelomic VE is maintained only at neutral pH, and is not visibly altered by the cortical reaction. VEs from coelomic eggs retain their fasciculated morphology after isolation from the egg. In an in vitro test system, sperm penetrated VEs isolated from oviposited eggs, but failed to penetrate VEs isolated from coelomic eggs. The structural transformation of the VE from the coelomic type to the oviposited type occurs in the first 1-cm segment of the oviduct, prior to addition of jelly to the egg. Neither intact jelly, solubilized jelly, nor jelly extracts were capable of altering the structural organization of coelomic VEs, suggesting that the structural transformation of the VE is effected by some oviducal factor other than jelly.", "contents": "Alteration of structure and penetrability of the vitelline envelope after passage of eggs from coelom to oviduct in Xenopus laevis. The vitelline envelope (VE) that surrounds an egg released from the ovary into the coelom of Xenopus laevis differs markedly, in structure and penetrability, from the VE surrounding an oviposited egg. In a coelomic egg, the filaments that form the VE are arranged in distinct fascicles or bundles. The exterior surface of the VE is irregular in contour and is permeated by channels. In an oviposited egg, the filaments are evenly dispersed and lack a fasciculated arrangement; the exterior surface is smooth and no channels are present. The fascicular arrangement of fibrils in the coelomic VE is maintained only at neutral pH, and is not visibly altered by the cortical reaction. VEs from coelomic eggs retain their fasciculated morphology after isolation from the egg. In an in vitro test system, sperm penetrated VEs isolated from oviposited eggs, but failed to penetrate VEs isolated from coelomic eggs. The structural transformation of the VE from the coelomic type to the oviposited type occurs in the first 1-cm segment of the oviduct, prior to addition of jelly to the egg. Neither intact jelly, solubilized jelly, nor jelly extracts were capable of altering the structural organization of coelomic VEs, suggesting that the structural transformation of the VE is effected by some oviducal factor other than jelly."}
{"id": "PMID:18550", "title": "Ribonucleotide reductase from herpes simplex virus (types 1 and 2) infected and uninfected KB cells: properties of the partially purified enzymes.", "content": "Mammalian ribonucleotide reductase is a complex enzyme modified in its activity by a complex regulatory system involving adenosine triphosphate (ATP) and deoxyribonucleoside triphosphates. Infection of KB cells with herpes simplex virus (HSV) type 1 or 2 induces the formation of an altered ribonucleotide reductase. The properties of partially purified reductase from uninfected KB cells have been compared with the enzymes obtained from HSV-1 and HSV-2 infected KB cells. We found that the virus-induced enzymes are similar to the KB enzyme in some properties but differed significantly from the host enzyme in three respects: (1) virus induced reductase was not inhibited significantly by deoxythymidine triphosphate regardless of ATP concentration, (2) magnesium was not required for virus enzyme activity although 2 mM-Mg2+ did stimulate the reaction, and (3) magnesium concentration required for optimal activity was different for virus and host enzymes. These changes are evidence that the enzyme molecules present after infection by HSV-1 or HSV-2 differ from those present before infection.", "contents": "Ribonucleotide reductase from herpes simplex virus (types 1 and 2) infected and uninfected KB cells: properties of the partially purified enzymes. Mammalian ribonucleotide reductase is a complex enzyme modified in its activity by a complex regulatory system involving adenosine triphosphate (ATP) and deoxyribonucleoside triphosphates. Infection of KB cells with herpes simplex virus (HSV) type 1 or 2 induces the formation of an altered ribonucleotide reductase. The properties of partially purified reductase from uninfected KB cells have been compared with the enzymes obtained from HSV-1 and HSV-2 infected KB cells. We found that the virus-induced enzymes are similar to the KB enzyme in some properties but differed significantly from the host enzyme in three respects: (1) virus induced reductase was not inhibited significantly by deoxythymidine triphosphate regardless of ATP concentration, (2) magnesium was not required for virus enzyme activity although 2 mM-Mg2+ did stimulate the reaction, and (3) magnesium concentration required for optimal activity was different for virus and host enzymes. These changes are evidence that the enzyme molecules present after infection by HSV-1 or HSV-2 differ from those present before infection."}
{"id": "PMID:18551", "title": "MMPI changes in briefly hospitalized non-narcotic drug users.", "content": "The Minnesota Multiphasic Personality Inventory (MMPI) was administered to 66 non-narcotic drug abusers as part of an intensive study of polydrug abuse. Patients were classified into four primary drug-of-abuse groups using either stimulants, barbiturates, other sedative-hypnotics, or a combination of these drugs. It was readministered to 42 of these patients after 2 weeks' hospitalization. At admission, the group's MMPI profile was consistent with psychosis. At discharge, most of the MMPI T-scores were sharply reduced, and the groups' profile was consistent with sociopathy. The admission MMPI profiles of the four primary drug-of-abuse groups did not differ. At discharge, the stimulant group's profile remained psychotic, while the profiles of the other three groups were not psychotic. Such results raise the possibility of a toxic psychotic effect of chronic non-narcotic drug abuse. The group of stimulant abusers appeared schizophrenic, while the other groups of non-narcotic drug abusers appeared sociopathic.", "contents": "MMPI changes in briefly hospitalized non-narcotic drug users. The Minnesota Multiphasic Personality Inventory (MMPI) was administered to 66 non-narcotic drug abusers as part of an intensive study of polydrug abuse. Patients were classified into four primary drug-of-abuse groups using either stimulants, barbiturates, other sedative-hypnotics, or a combination of these drugs. It was readministered to 42 of these patients after 2 weeks' hospitalization. At admission, the group's MMPI profile was consistent with psychosis. At discharge, most of the MMPI T-scores were sharply reduced, and the groups' profile was consistent with sociopathy. The admission MMPI profiles of the four primary drug-of-abuse groups did not differ. At discharge, the stimulant group's profile remained psychotic, while the profiles of the other three groups were not psychotic. Such results raise the possibility of a toxic psychotic effect of chronic non-narcotic drug abuse. The group of stimulant abusers appeared schizophrenic, while the other groups of non-narcotic drug abusers appeared sociopathic."}
{"id": "PMID:18552", "title": "Inhibition of catecholamine release by alpha-adrenergic activation: interaction with Na, K-ATPase.", "content": "In rat adrenal gland incubated in vitro, phenylephrine and naphazoline inhibited the release of catecholamines (CA) induced in a medium containing K+ (5.6mM). In K+-free medium or in the presence of ouabain (10(-3) M) phenylephrine and naphazoline had no effect on CA release. The alpha-adrenergic blockers, phentolamine and phenoxybenzamine, increased CA release in a K+-medium but had no effect on CA release from adrenal medulla in a K+-free or ouabain (10(-3) M) containing medium. PGE2 inhibited the release of CA both in the presence and in the absence of K+, as well as in the presence of ouabain (10(-3) M). Activation of alpha-adrenergic receptors in the adrenal medulla by phenylephrine and naphazoline resulted in increased Na, K-ATPase activity but no effect on Mg-ATPase. PGE2 acts through a different mechanism.", "contents": "Inhibition of catecholamine release by alpha-adrenergic activation: interaction with Na, K-ATPase. In rat adrenal gland incubated in vitro, phenylephrine and naphazoline inhibited the release of catecholamines (CA) induced in a medium containing K+ (5.6mM). In K+-free medium or in the presence of ouabain (10(-3) M) phenylephrine and naphazoline had no effect on CA release. The alpha-adrenergic blockers, phentolamine and phenoxybenzamine, increased CA release in a K+-medium but had no effect on CA release from adrenal medulla in a K+-free or ouabain (10(-3) M) containing medium. PGE2 inhibited the release of CA both in the presence and in the absence of K+, as well as in the presence of ouabain (10(-3) M). Activation of alpha-adrenergic receptors in the adrenal medulla by phenylephrine and naphazoline resulted in increased Na, K-ATPase activity but no effect on Mg-ATPase. PGE2 acts through a different mechanism."}
{"id": "PMID:18553", "title": "Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems.", "content": "Locomotor stimulation induced in mice by morphine and amphetamine was antagonized by pretreatment with gamma-butyrolactone (GBL) and amino-oxyacetic acid (AOAA) at doses which had little effect on saline treated animals. The effects of morphine and AOAA on the turnover of brain catecholamines (CA) were determined by measuring both the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase and by measuring the depletion of noradrenaline (NA) after inhibition of tyrosine hydroxylase by alpha-methyltyrosine (alpha-MT). Morphine and AOAA were found to have opposite effects on CA turnover, i.e. morphine caused an increase and AOAA, a decrease. AOAA also antagonized the morphine-induced increase in CA turnover. These data might suggest that the well documented ability of GABAergic drugs to inhibit the firing of DA-containing neurons may be of importance in explaining the present findings. However, the locomotor stimulation induced by the directly-acting CA agonists, apomorphine and clonidine after pretreatment with reserpine and alpha-MT was also inhibited by the GABAergic drugs. It is therefore concluded that the suppressant effects of the GABAergic agents on hypermotility and not solely mediated by their effects on presynaptic CA mechanisms, but also by a postsynaptic inhibition at some point beyond the CA neurons.", "contents": "Suppression by GABAergic drugs of the locomotor stimulation induced by morphine, amphetamine, and apomorphine: evidence for both pre- and post-synaptic inhibition of catecholamine systems. Locomotor stimulation induced in mice by morphine and amphetamine was antagonized by pretreatment with gamma-butyrolactone (GBL) and amino-oxyacetic acid (AOAA) at doses which had little effect on saline treated animals. The effects of morphine and AOAA on the turnover of brain catecholamines (CA) were determined by measuring both the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase and by measuring the depletion of noradrenaline (NA) after inhibition of tyrosine hydroxylase by alpha-methyltyrosine (alpha-MT). Morphine and AOAA were found to have opposite effects on CA turnover, i.e. morphine caused an increase and AOAA, a decrease. AOAA also antagonized the morphine-induced increase in CA turnover. These data might suggest that the well documented ability of GABAergic drugs to inhibit the firing of DA-containing neurons may be of importance in explaining the present findings. However, the locomotor stimulation induced by the directly-acting CA agonists, apomorphine and clonidine after pretreatment with reserpine and alpha-MT was also inhibited by the GABAergic drugs. It is therefore concluded that the suppressant effects of the GABAergic agents on hypermotility and not solely mediated by their effects on presynaptic CA mechanisms, but also by a postsynaptic inhibition at some point beyond the CA neurons."}
{"id": "PMID:18565", "title": "Metabolic fate of cyanocobalamin taken up by Spirometra mansonoides spargana.", "content": "Analysis of tissue from Spirometra mansonoides spargana has shown that cyanocobalamin (vitamin B12) is metabolized to adenosylcobalamin and hydroxocobalamin. No methylcobalamin was detected. When the tissues were examined for enzymes which are known to utilize coenzyme forms of vitamin B12, only methylmalonyl CoA mutase, which requires adenosylcobalamin was found. The enzyme, tetrahydropteroylglutamate methyltransferase, which requires methylcobalamin as a cofactor, was not detected. A sizable portion of the cyanocobalamin taken up was bound to ammonium sulfate-precipitable material, suggesting that the binding substance is a protein. Vitamin B12 taken up by spargana was found to be released in vivo with a biological half-life of about 7 weeks.", "contents": "Metabolic fate of cyanocobalamin taken up by Spirometra mansonoides spargana. Analysis of tissue from Spirometra mansonoides spargana has shown that cyanocobalamin (vitamin B12) is metabolized to adenosylcobalamin and hydroxocobalamin. No methylcobalamin was detected. When the tissues were examined for enzymes which are known to utilize coenzyme forms of vitamin B12, only methylmalonyl CoA mutase, which requires adenosylcobalamin was found. The enzyme, tetrahydropteroylglutamate methyltransferase, which requires methylcobalamin as a cofactor, was not detected. A sizable portion of the cyanocobalamin taken up was bound to ammonium sulfate-precipitable material, suggesting that the binding substance is a protein. Vitamin B12 taken up by spargana was found to be released in vivo with a biological half-life of about 7 weeks."}
{"id": "PMID:18568", "title": "The pharmacology of benoxaprofen (2-[4-chlorophenyl]-alpha-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with antiinflammatory activity apparently unrelated to inhibition of prostaglandin synthesis.", "content": "Benoxaprofen is a potent and long-acting anti-inflammatory and antipyretic compound. Its anti-inflammatory activity has been demonstrated in carrageenan-induced oedema, in cellulose pellet granuloma and in both developing and established adjuvant arthritis tests in rats. Its antipyretic activity is greater than either aspirin or paracetamol in tests inducing pyrexia with yeast of 'E' pyrogen in rats and rabbits. Benoxaprofen has analgesic activity in tests where pain is accompanied by inflammation but not in other experimental models of pain. The weak prostaglandin synthetase inhibiting properties of this compound differentiate it from other acid anti-inflammatory compounds. The low ulcerogenic potential of benoxaprofen seen in animal models may be related to its relative inability to inhibit PG synthetase.", "contents": "The pharmacology of benoxaprofen (2-[4-chlorophenyl]-alpha-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with antiinflammatory activity apparently unrelated to inhibition of prostaglandin synthesis. Benoxaprofen is a potent and long-acting anti-inflammatory and antipyretic compound. Its anti-inflammatory activity has been demonstrated in carrageenan-induced oedema, in cellulose pellet granuloma and in both developing and established adjuvant arthritis tests in rats. Its antipyretic activity is greater than either aspirin or paracetamol in tests inducing pyrexia with yeast of 'E' pyrogen in rats and rabbits. Benoxaprofen has analgesic activity in tests where pain is accompanied by inflammation but not in other experimental models of pain. The weak prostaglandin synthetase inhibiting properties of this compound differentiate it from other acid anti-inflammatory compounds. The low ulcerogenic potential of benoxaprofen seen in animal models may be related to its relative inability to inhibit PG synthetase."}
{"id": "PMID:18571", "title": "The in vitro metabolism of 2-nitroso-1-phenylpropane dimer by fortified 9000g supernatants from rabbit liver.", "content": "2-Nitroso-1-phenylpropane dimer, a postulated metabolic product of amphetamine, was metabolized by fortified 9000 g supernatants from rabbit liver, mainly by oxidation on the carbon beta to the nitrogen to form a \"beta-hydroxylated nitroso dimer'. The corresponding nitro compound, ketone and alcohol were also products, the latter two but not the former being cofactor dependent. The nitroso compound was not metabolically reduced under the conditions used.", "contents": "The in vitro metabolism of 2-nitroso-1-phenylpropane dimer by fortified 9000g supernatants from rabbit liver. 2-Nitroso-1-phenylpropane dimer, a postulated metabolic product of amphetamine, was metabolized by fortified 9000 g supernatants from rabbit liver, mainly by oxidation on the carbon beta to the nitrogen to form a \"beta-hydroxylated nitroso dimer'. The corresponding nitro compound, ketone and alcohol were also products, the latter two but not the former being cofactor dependent. The nitroso compound was not metabolically reduced under the conditions used."}
{"id": "PMID:18572", "title": "Application of orthogonal functions to the spectrophotometric determination of phenytoin and phenobarbitone in pharmaceutical preparations.", "content": "Orthogonal polynomial functions have been used in the simultaneous determination of mixtures of phenytoin and phenobarbitone in pharmaceutical preparations. The mean recovery (9 determinations) and coefficeint of variation were 100-0 +/- 1-4% for phenobarbitone and 100-0 +/-1-3% for phenytoin. Neither the delta A method of Pannerdan & Fontein nor a delta A modification of Vierordt's method of two-component analysis gave results of the same accuracy and precision as the proposed method.", "contents": "Application of orthogonal functions to the spectrophotometric determination of phenytoin and phenobarbitone in pharmaceutical preparations. Orthogonal polynomial functions have been used in the simultaneous determination of mixtures of phenytoin and phenobarbitone in pharmaceutical preparations. The mean recovery (9 determinations) and coefficeint of variation were 100-0 +/- 1-4% for phenobarbitone and 100-0 +/-1-3% for phenytoin. Neither the delta A method of Pannerdan & Fontein nor a delta A modification of Vierordt's method of two-component analysis gave results of the same accuracy and precision as the proposed method."}
{"id": "PMID:18573", "title": "Autoxidation of N-hydroxyphenylalkylamines: the inhibitory effect of some anions on copper catalysed  autoxidation of N-hydroxyphentermine.", "content": "The inhibitory effect of certain electrolytes and buffers on the copper catalysed autoxidation of N-hydroxyphentermine (2-hydroxylamino-2-methyl-1-phenylpropane) has been investigated. The presence of ions such as SO4(2-), Cl- or Br- markedly reduced the rate of oxidation. Phosphate and carbonate buffers had a similar effect with halides and phosphate buffers being the most inhibitory. The occurence of 2-methyl-2-nitro-1-phenylpropane and 2-methyl-1-phenylpropene-(1) as secondary oxidation products was also established.", "contents": "Autoxidation of N-hydroxyphenylalkylamines: the inhibitory effect of some anions on copper catalysed  autoxidation of N-hydroxyphentermine. The inhibitory effect of certain electrolytes and buffers on the copper catalysed autoxidation of N-hydroxyphentermine (2-hydroxylamino-2-methyl-1-phenylpropane) has been investigated. The presence of ions such as SO4(2-), Cl- or Br- markedly reduced the rate of oxidation. Phosphate and carbonate buffers had a similar effect with halides and phosphate buffers being the most inhibitory. The occurence of 2-methyl-2-nitro-1-phenylpropane and 2-methyl-1-phenylpropene-(1) as secondary oxidation products was also established."}
{"id": "PMID:18574", "title": "Generated surface area measurement of disintegrating tablets.", "content": "The surface areas generated by the disintegration and dissolution of six commercial brands of phenylbutazone tablets B.P. 100 mg have been measured using a Model TA Coulter Counter. The graphs of surface area generated against time were all of the same shape and always reached a maximum value. The initial surface area increase was due to tablet disintegration and deaggregation and followed first order kinetics. A good correlation between the slope of this initial increase and disintegration time was found. The maximum surface area generated correlated at the probability level of better than 99-9% with the dissolution rat measured as t60. The subsequent decrease in surface area, after this maximum, was considered to be due to phenylbutazone dissolution and was also first order rate controlled.", "contents": "Generated surface area measurement of disintegrating tablets. The surface areas generated by the disintegration and dissolution of six commercial brands of phenylbutazone tablets B.P. 100 mg have been measured using a Model TA Coulter Counter. The graphs of surface area generated against time were all of the same shape and always reached a maximum value. The initial surface area increase was due to tablet disintegration and deaggregation and followed first order kinetics. A good correlation between the slope of this initial increase and disintegration time was found. The maximum surface area generated correlated at the probability level of better than 99-9% with the dissolution rat measured as t60. The subsequent decrease in surface area, after this maximum, was considered to be due to phenylbutazone dissolution and was also first order rate controlled."}
{"id": "PMID:18591", "title": "Hydrolysis and epimerization kinetics of hetacillin in aqueous solution.", "content": "Methods were developed for quantitating epimerization to epihetacillin and hydrolysis to ampicillin in the alkaline degradation of hetacillin, and both rates in deuterium oxide at 35 degrees and in water at various temperatures were determined. In each case, plots of log k for the epimerization against pH or pD yielded straight lines with a positive slope, which verified the first-order dependence on the hydroxide ion or deuteroxide ion. The activation energy of the epimerization process was 21.2 kcal/mole. In aqueous solution at high pH, epimerization rather than conversion to ampicillin represents a major pathway of hetacillin degradation, although the beta-lactam ring of the hetacillin molecule is highly resistant to attack by the hydroxide ion.", "contents": "Hydrolysis and epimerization kinetics of hetacillin in aqueous solution. Methods were developed for quantitating epimerization to epihetacillin and hydrolysis to ampicillin in the alkaline degradation of hetacillin, and both rates in deuterium oxide at 35 degrees and in water at various temperatures were determined. In each case, plots of log k for the epimerization against pH or pD yielded straight lines with a positive slope, which verified the first-order dependence on the hydroxide ion or deuteroxide ion. The activation energy of the epimerization process was 21.2 kcal/mole. In aqueous solution at high pH, epimerization rather than conversion to ampicillin represents a major pathway of hetacillin degradation, although the beta-lactam ring of the hetacillin molecule is highly resistant to attack by the hydroxide ion."}
{"id": "PMID:18592", "title": "Actions of mescaline on isolated rat atria.", "content": "Mescaline, in concentrations of 5 x 10(-4) and 1 x 10(-3) M, produced negative chronotropic and positive inotropic responses in isolated, spontaneously beating rat atria. In tissues driven at a constant rate, the inotropic response was diminished greatly, indicating that the increment in the force of contraction was secondary to the reduction in rate. These chronotropic and inotropic responses were not altered consistently by pretreatment with the histamine antagonists chlorpheniramine and metiamide.", "contents": "Actions of mescaline on isolated rat atria. Mescaline, in concentrations of 5 x 10(-4) and 1 x 10(-3) M, produced negative chronotropic and positive inotropic responses in isolated, spontaneously beating rat atria. In tissues driven at a constant rate, the inotropic response was diminished greatly, indicating that the increment in the force of contraction was secondary to the reduction in rate. These chronotropic and inotropic responses were not altered consistently by pretreatment with the histamine antagonists chlorpheniramine and metiamide."}
{"id": "PMID:18593", "title": "Electronic absorption spectra and protolytic equilibria of doxorubicin: direct spectrophotometric determination of microconstants.", "content": "The ground- and excited-state dissociation constants and the electronic absorption and fluorescence spectra of doxorubicin were investigated by spectrophotometry. A general method for the direct calculation of individual microscopic dissociation constants was derived using the spectrophotometric data obtained. It was concluded that the protonated amino sugar group is slightly more acidic than the phenolic group. The spectrophotometric data were analyzed, and the macro- and microconstants for the various equilibria was reported.", "contents": "Electronic absorption spectra and protolytic equilibria of doxorubicin: direct spectrophotometric determination of microconstants. The ground- and excited-state dissociation constants and the electronic absorption and fluorescence spectra of doxorubicin were investigated by spectrophotometry. A general method for the direct calculation of individual microscopic dissociation constants was derived using the spectrophotometric data obtained. It was concluded that the protonated amino sugar group is slightly more acidic than the phenolic group. The spectrophotometric data were analyzed, and the macro- and microconstants for the various equilibria was reported."}
{"id": "PMID:18594", "title": "Solubility and ionization characteristics of phenytoin.", "content": "The solubility of phenytoin was determined in pH 7.4 and 5.4 phosphate buffers at five temperatures; in hydroalcoholic solutions, 0--4% methanol; and in pH 4.8--8.4 buffer solutions. From the temperature data, the enthalpy and entropy of solution of this nonideal system were calculated and were similar at both pH values. The data obtained from the buffer solutions were used to calculate the apparent dissociation constant, pKa', of phenytoin as 8.06. A GLC method with on-column methylation was used to quantitate phenytoin with 5-(p-methyl-phenyl)-5-phenylhydantoin as an internal standard. The assay uses chloroform of extraction of the drug from aqueous solutions. The ratio of peak heights was adjusted for weights of aqueous and organic layers, and results were calculated in micrograms per gram of sample and mole fraction of phenytoin. Although hydroalcoholic solutions enhanced drug solubility, there is a potentially significant disadvantage in using alcohol for clinical studies.", "contents": "Solubility and ionization characteristics of phenytoin. The solubility of phenytoin was determined in pH 7.4 and 5.4 phosphate buffers at five temperatures; in hydroalcoholic solutions, 0--4% methanol; and in pH 4.8--8.4 buffer solutions. From the temperature data, the enthalpy and entropy of solution of this nonideal system were calculated and were similar at both pH values. The data obtained from the buffer solutions were used to calculate the apparent dissociation constant, pKa', of phenytoin as 8.06. A GLC method with on-column methylation was used to quantitate phenytoin with 5-(p-methyl-phenyl)-5-phenylhydantoin as an internal standard. The assay uses chloroform of extraction of the drug from aqueous solutions. The ratio of peak heights was adjusted for weights of aqueous and organic layers, and results were calculated in micrograms per gram of sample and mole fraction of phenytoin. Although hydroalcoholic solutions enhanced drug solubility, there is a potentially significant disadvantage in using alcohol for clinical studies."}
{"id": "PMID:18595", "title": "Determination of acenocoumarol in plasma and urine by double radioisotope derivative analysis.", "content": "Acenocoumarol, to which a 14C-labeled internal standard has been added, is extracted at pH 4 into ethyl acetate-heptane (20:80 v/v), back-extracted into aqueous sodium hydroxide solution after solvent washing with a pH 7 buffer, and reextracted after acidification in the solvent mixture. It is then acetylated with 3H-acetic anhydride. The acenocoumarol acetyl derivative is separated from the metabolite derivatives by TLC, and its radioactivity is measured. The method is specific and sensitive to a concentration of 8 ng/ml.", "contents": "Determination of acenocoumarol in plasma and urine by double radioisotope derivative analysis. Acenocoumarol, to which a 14C-labeled internal standard has been added, is extracted at pH 4 into ethyl acetate-heptane (20:80 v/v), back-extracted into aqueous sodium hydroxide solution after solvent washing with a pH 7 buffer, and reextracted after acidification in the solvent mixture. It is then acetylated with 3H-acetic anhydride. The acenocoumarol acetyl derivative is separated from the metabolite derivatives by TLC, and its radioactivity is measured. The method is specific and sensitive to a concentration of 8 ng/ml."}
{"id": "PMID:18596", "title": "Kinetics of accumulation, efflux and the pharmacological effects of tritiated dihydroazapetine on the rabbit aorta.", "content": "Azepatine, a potent alpha adrenergic antagonist, was catalytically reduced with tritium and hydrogen gas to form dihydroazapetine. The pA2 azapetine was 7.9 whereas that of dihydroazapetine was 6.6, corresponding to a 20-fold decrease in potency. 3H-dihydroazapetine is accumulated into three kinetically distinct compartment in the denervated rabbit aorta. Likewise, efflux of the labeled antagonist occurs from three compartments. The rat constant for onset of alpha adrenoreceptor blockade is 3.15 min-1 which is nearly identical to the rate constant for entry of 3H-dihydroazapetine into a rapidly filling compartment (3.86 min-1) possibly representing the extracellular space. These data are consistent with the hypothesis that onset of alpha adrenoreceptor blockade by dihydroazapetine is diffusion limited.", "contents": "Kinetics of accumulation, efflux and the pharmacological effects of tritiated dihydroazapetine on the rabbit aorta. Azepatine, a potent alpha adrenergic antagonist, was catalytically reduced with tritium and hydrogen gas to form dihydroazapetine. The pA2 azapetine was 7.9 whereas that of dihydroazapetine was 6.6, corresponding to a 20-fold decrease in potency. 3H-dihydroazapetine is accumulated into three kinetically distinct compartment in the denervated rabbit aorta. Likewise, efflux of the labeled antagonist occurs from three compartments. The rat constant for onset of alpha adrenoreceptor blockade is 3.15 min-1 which is nearly identical to the rate constant for entry of 3H-dihydroazapetine into a rapidly filling compartment (3.86 min-1) possibly representing the extracellular space. These data are consistent with the hypothesis that onset of alpha adrenoreceptor blockade by dihydroazapetine is diffusion limited."}
{"id": "PMID:18599", "title": "Differences in pulmonary and cardiovascular beta receptors in the guinea pig and rabbit.", "content": "An in vivo preparation, in which a body plethysmograph was incorporated, was useful in monitoring the cardiopulmonary effects of pharmacological agents in the guinea pig and rabbit. Isoproterenol, given 30 seconds prior to histamine challenge, reproducibly blocked histamine-induced dynamic compliance decreases and increased heart in the artificially ventilated guinea pig. These effects were used to separate the activity of beta adrenergic blockers on airway and heart muscle. Dose-response data were obtained and ED50 values for pulmonary and cardiovascular blockade were compared. Relative potencies and cardioselectivity ratios for dichloroisoproterenol, practolol, dl-propranolol and d-propranolol were determined. Both practolol and dichloroisoproterenol were cardioselective; dl-propranolol was found to be the most potent. When a similar protocol was tried in the rabbit, isorpoterenol failed to antagonize either histamine or methacholine-induced airway constriction. This finding was supported in subsequent in vitro tests. Isoproterenol and epinephrine were ineffective in blocking methacholine-induced tracheal chain contractions and epinephrine did not significantly enhance adenylate cyclase activity. Our observations suggest rabbit airway smooth muscle is insensitive to beta adrenergic stimulants.", "contents": "Differences in pulmonary and cardiovascular beta receptors in the guinea pig and rabbit. An in vivo preparation, in which a body plethysmograph was incorporated, was useful in monitoring the cardiopulmonary effects of pharmacological agents in the guinea pig and rabbit. Isoproterenol, given 30 seconds prior to histamine challenge, reproducibly blocked histamine-induced dynamic compliance decreases and increased heart in the artificially ventilated guinea pig. These effects were used to separate the activity of beta adrenergic blockers on airway and heart muscle. Dose-response data were obtained and ED50 values for pulmonary and cardiovascular blockade were compared. Relative potencies and cardioselectivity ratios for dichloroisoproterenol, practolol, dl-propranolol and d-propranolol were determined. Both practolol and dichloroisoproterenol were cardioselective; dl-propranolol was found to be the most potent. When a similar protocol was tried in the rabbit, isorpoterenol failed to antagonize either histamine or methacholine-induced airway constriction. This finding was supported in subsequent in vitro tests. Isoproterenol and epinephrine were ineffective in blocking methacholine-induced tracheal chain contractions and epinephrine did not significantly enhance adenylate cyclase activity. Our observations suggest rabbit airway smooth muscle is insensitive to beta adrenergic stimulants."}
{"id": "PMID:18601", "title": "Phosphofructokinase of Leishmania donovani and Leishmania braziliensis and its role in glycolysis.", "content": "It was shown in an investigation of the phosphofructokinases of Leishmania donovani and Leishmania braziliensis that both enzymes are similar to that of Crithidia fasciculata. Although the enzymes are allosteric with respect to their substrates and require AMP for activation, there is no influence by other heterotropic modifiers. The Mg2+-ATP chelate activates these enzymes in a first order process and they can be inhibited by free ATP. The inhibition is reversed by the activator, AMP, in a competitive manner. The requirement for the nucleotide in L. donovani can be eliminated by decreasing the pH. The data indicate that phosphofructokinase, a pivotal enzyme in glycolysis for most organisms, probably does not play an important role in glycolysis in Leishmania.", "contents": "Phosphofructokinase of Leishmania donovani and Leishmania braziliensis and its role in glycolysis. It was shown in an investigation of the phosphofructokinases of Leishmania donovani and Leishmania braziliensis that both enzymes are similar to that of Crithidia fasciculata. Although the enzymes are allosteric with respect to their substrates and require AMP for activation, there is no influence by other heterotropic modifiers. The Mg2+-ATP chelate activates these enzymes in a first order process and they can be inhibited by free ATP. The inhibition is reversed by the activator, AMP, in a competitive manner. The requirement for the nucleotide in L. donovani can be eliminated by decreasing the pH. The data indicate that phosphofructokinase, a pivotal enzyme in glycolysis for most organisms, probably does not play an important role in glycolysis in Leishmania."}
{"id": "PMID:18603", "title": "Nature of the rabbit acrosome reaction-inducing activity of follicular fluid.", "content": "Follicular fluid samples from rabbits, cats, pigs, women and cows had acrosome reaction-inducing activity (ARIA) on rabbit spermatozoa as determined by differential staining after incubation with these fluids. Activity was retained after dialysis and at least 50% was found to be labile when heated to 56 degrees C for as little as 20 min. The induction of the acrosome reaction by bovine follicular fluid showed a dependence on the concentration of follicular fluid and spermatozoa and on calcium ions, and had a pH optimum of approximately 8. Enzyme treatments showed that proteases destroyed the ARIA and this activity was completely blocked by treatment of bovine follicular fluid with goat anti-bovine antiserum. Electron microscope observations indicated the similarity of the reactions observed to that occurring in vivo. It is concluded that the rabbit acrosome reaction inducing-activity of bovine follicular fluid is a serum component(s), probably a protein(s) of high molecular weight.", "contents": "Nature of the rabbit acrosome reaction-inducing activity of follicular fluid. Follicular fluid samples from rabbits, cats, pigs, women and cows had acrosome reaction-inducing activity (ARIA) on rabbit spermatozoa as determined by differential staining after incubation with these fluids. Activity was retained after dialysis and at least 50% was found to be labile when heated to 56 degrees C for as little as 20 min. The induction of the acrosome reaction by bovine follicular fluid showed a dependence on the concentration of follicular fluid and spermatozoa and on calcium ions, and had a pH optimum of approximately 8. Enzyme treatments showed that proteases destroyed the ARIA and this activity was completely blocked by treatment of bovine follicular fluid with goat anti-bovine antiserum. Electron microscope observations indicated the similarity of the reactions observed to that occurring in vivo. It is concluded that the rabbit acrosome reaction inducing-activity of bovine follicular fluid is a serum component(s), probably a protein(s) of high molecular weight."}
{"id": "PMID:18606", "title": "Experimental E. coli arthritis in the rabbit. A model of infectious and post-infectious inflammatory synovitis.", "content": "Rabbit knee joints challenged with E. coli 06 underwent a self-limited infection lasting several weeks followed by a prolonged post-infectious inflammatory arthritis. The E. coli used did not possess collagenolytic activity nor did a variety of common aerobic clinical isolates. Articular cartilage destruction occurred by two basically different mechanisms: u) direct invasion of pannus at the juxtaarticular margins, and 2) fibrillation in cartilage to cartilage contact areas. Weekly measurement of intra-articular pH and temperature were correlated with bacteriologic findings and groww and microscopic pathologic events.", "contents": "Experimental E. coli arthritis in the rabbit. A model of infectious and post-infectious inflammatory synovitis. Rabbit knee joints challenged with E. coli 06 underwent a self-limited infection lasting several weeks followed by a prolonged post-infectious inflammatory arthritis. The E. coli used did not possess collagenolytic activity nor did a variety of common aerobic clinical isolates. Articular cartilage destruction occurred by two basically different mechanisms: u) direct invasion of pannus at the juxtaarticular margins, and 2) fibrillation in cartilage to cartilage contact areas. Weekly measurement of intra-articular pH and temperature were correlated with bacteriologic findings and groww and microscopic pathologic events."}
{"id": "PMID:18608", "title": "An analysis of the professional performance of physician's assistants.", "content": "The job performance of a national sample of 939 physician's assistants has been assessed by means of a self-rating scale as well as by a rating scale completed by supervising physicians. Three-quarters of the participating supervising physicians are greatly satisfied with the work of their physician's assistants and a similar proportion indicate that they would definitely hire the same assistant if they \"had it to do over again.\" The influences of background and work environment characteristics upon performance were assessed by means of multiple regression. Graduating from a military-sponsored physician's assistant program appears to have a beneficial effect upon performance. Performance during training exerts only a weak effect upon job performance. Amount of education and medical experience prior to beginning physician's assistant training do not affect job performance.", "contents": "An analysis of the professional performance of physician's assistants. The job performance of a national sample of 939 physician's assistants has been assessed by means of a self-rating scale as well as by a rating scale completed by supervising physicians. Three-quarters of the participating supervising physicians are greatly satisfied with the work of their physician's assistants and a similar proportion indicate that they would definitely hire the same assistant if they \"had it to do over again.\" The influences of background and work environment characteristics upon performance were assessed by means of multiple regression. Graduating from a military-sponsored physician's assistant program appears to have a beneficial effect upon performance. Performance during training exerts only a weak effect upon job performance. Amount of education and medical experience prior to beginning physician's assistant training do not affect job performance."}
{"id": "PMID:18614", "title": "Glycosidase susceptibility: a probe for the distribution of glycoprotein oligosaccharides in Sindbis virus.", "content": "Intact Sindbis virus and Triton-solubilized viral glycoprotein were treated with alpha-mannosidase and with a preparation of mixed glycosidases from Diplococcus pneumoniae to probe the accesibility of carbohydrate units on the viral surface. The products of glycosidase attack on Triton-solubilized virus showed that mose carbohydrate units of the glycoproteins are good substrates for these enzymes. The relative resistance of most of the viral oligosaccharides in intact virus particles showed that much of the carbohydrate is not accessible to glycosidases, probably because it is not exposed at the viral surface. The only completely accessible carbohydrate units on Sindbis glycoproteins were the type A oligosaccharides of E2. This differential accessibility of Sindbis oligosaccharides is discussed in relation to the organization of the viral surface.", "contents": "Glycosidase susceptibility: a probe for the distribution of glycoprotein oligosaccharides in Sindbis virus. Intact Sindbis virus and Triton-solubilized viral glycoprotein were treated with alpha-mannosidase and with a preparation of mixed glycosidases from Diplococcus pneumoniae to probe the accesibility of carbohydrate units on the viral surface. The products of glycosidase attack on Triton-solubilized virus showed that mose carbohydrate units of the glycoproteins are good substrates for these enzymes. The relative resistance of most of the viral oligosaccharides in intact virus particles showed that much of the carbohydrate is not accessible to glycosidases, probably because it is not exposed at the viral surface. The only completely accessible carbohydrate units on Sindbis glycoproteins were the type A oligosaccharides of E2. This differential accessibility of Sindbis oligosaccharides is discussed in relation to the organization of the viral surface."}
{"id": "PMID:18616", "title": "Acute purulent otitis media in children older than 5 years. Incidence of Haemophilus as a causative organism.", "content": "It is generally believed that Haemophilus influenzae is not commonly a causative agent of otitis media in children older than 5 years of age. We recently studied cases of 58 children, aged from 5 to 9 years, who had acute otitis media. Haemophilus species were the causative agents in 36% of cases. This high incidence of Haemophilus isolation from the middle ear exudate of these children has important therapeutic implications; antibiotics effective against H influenzae should be employed when dealing with otitis media in this older age group.", "contents": "Acute purulent otitis media in children older than 5 years. Incidence of Haemophilus as a causative organism. It is generally believed that Haemophilus influenzae is not commonly a causative agent of otitis media in children older than 5 years of age. We recently studied cases of 58 children, aged from 5 to 9 years, who had acute otitis media. Haemophilus species were the causative agents in 36% of cases. This high incidence of Haemophilus isolation from the middle ear exudate of these children has important therapeutic implications; antibiotics effective against H influenzae should be employed when dealing with otitis media in this older age group."}
{"id": "PMID:18618", "title": "Severe combined immunodeficiency disease. Characterization of the disease and results of transplantation.", "content": "Pretransplant and posttransplant data for 69 patients with severe combined immunodeficiency disease are presented. Both B and T lymphocyte functions were absent in approximately 80% of the children and markedly depressed in the remainder. Transplantation of marrow from HLA genotypically identical donors provided the highest six-month survival rate (63%); six-month survival rates for patients who received fetal tissue transplants (43%) or marrow from mixed leukocyte culture (MLC) negative donors (38%) were significantly higher (P less than .05) than for patients treated with marrow from MLC positive donors (5%). Additional factors appeared to influence survival and the severity of graft-vs-host (GVH) disease. Patients more than 6 months of age had more intense GVH disease than younger patients. Survival rates  were lower and GVH disease more intense when boys received transplants from girl donors than the reverse.", "contents": "Severe combined immunodeficiency disease. Characterization of the disease and results of transplantation. Pretransplant and posttransplant data for 69 patients with severe combined immunodeficiency disease are presented. Both B and T lymphocyte functions were absent in approximately 80% of the children and markedly depressed in the remainder. Transplantation of marrow from HLA genotypically identical donors provided the highest six-month survival rate (63%); six-month survival rates for patients who received fetal tissue transplants (43%) or marrow from mixed leukocyte culture (MLC) negative donors (38%) were significantly higher (P less than .05) than for patients treated with marrow from MLC positive donors (5%). Additional factors appeared to influence survival and the severity of graft-vs-host (GVH) disease. Patients more than 6 months of age had more intense GVH disease than younger patients. Survival rates  were lower and GVH disease more intense when boys received transplants from girl donors than the reverse."}
{"id": "PMID:18620", "title": "Nephropathia epidemica. The Scandinavian form of hemorrhagic fever with renal syndrome.", "content": "We report epidemiologic, clinical, laboratory, and biopsy findings in 14 cases of nephropathia epidemica. The patients were between 19 and 49 years of age. The onset of the disease was characterized by high fever, nausea, headache, backache, abdominal pain, proteinuria, oliguria, hematuria, and uremia. The symptoms subsided rapidly during the polyuria phase, which followed the oliguria stage. Because of renal failure, hemodialysis was required in eight cases. Edema of eyelids, conjunctival injection and hemorrhages, transitory myopia, and acute glaucoma were the most common eye abnormalities. Renal biopsy specimens showed glomerular changes, with mild swelling of the epithelial cells of Bowman's capsule, thickening of the basement membrane of glomerular capillaries, glomerular adhesions, inflammatory cell infiltration, leukocytoclasis and hemorrhages in the interstitium, and eosinophilic hyaline degeneration and vacuolization of the epithelial cells of the proximal tubuli.", "contents": "Nephropathia epidemica. The Scandinavian form of hemorrhagic fever with renal syndrome. We report epidemiologic, clinical, laboratory, and biopsy findings in 14 cases of nephropathia epidemica. The patients were between 19 and 49 years of age. The onset of the disease was characterized by high fever, nausea, headache, backache, abdominal pain, proteinuria, oliguria, hematuria, and uremia. The symptoms subsided rapidly during the polyuria phase, which followed the oliguria stage. Because of renal failure, hemodialysis was required in eight cases. Edema of eyelids, conjunctival injection and hemorrhages, transitory myopia, and acute glaucoma were the most common eye abnormalities. Renal biopsy specimens showed glomerular changes, with mild swelling of the epithelial cells of Bowman's capsule, thickening of the basement membrane of glomerular capillaries, glomerular adhesions, inflammatory cell infiltration, leukocytoclasis and hemorrhages in the interstitium, and eosinophilic hyaline degeneration and vacuolization of the epithelial cells of the proximal tubuli."}
{"id": "PMID:18623", "title": "Pharmacologic analysis of stretch-induced sinus acceleration of the isolated dog atrium.", "content": "Using isolated, blood-perfused atrium preparation of the dogs, the effect of stretch on sinus rate was studied in 11 preparations. Stretching usually produced sinus acceleration in all 11 spontaneously beating atria. Within a range of 0--30 Gm, greater degrees of stretch produced greater degrees of sinus acceleration. During maintained stretch sinus rate slightly reduced but not to the control rate. On release from stretch sinus rate immediately returned to the control rate, and there was occasionally a slowing to rates lower than control in verapamil treated preparations. Atropine, adrenergic beta-receptor blocking agents, propranolol and carteolol, verapamil, and tetrodotoxin did not greatly modify responses to stretching.", "contents": "Pharmacologic analysis of stretch-induced sinus acceleration of the isolated dog atrium. Using isolated, blood-perfused atrium preparation of the dogs, the effect of stretch on sinus rate was studied in 11 preparations. Stretching usually produced sinus acceleration in all 11 spontaneously beating atria. Within a range of 0--30 Gm, greater degrees of stretch produced greater degrees of sinus acceleration. During maintained stretch sinus rate slightly reduced but not to the control rate. On release from stretch sinus rate immediately returned to the control rate, and there was occasionally a slowing to rates lower than control in verapamil treated preparations. Atropine, adrenergic beta-receptor blocking agents, propranolol and carteolol, verapamil, and tetrodotoxin did not greatly modify responses to stretching."}
{"id": "PMID:18629", "title": "A comparative study of the effects of OPC-1085 and propranolol on isolated guinea pig atrium.", "content": "Effects of a newly synthesized beta-blocker, 5-(3-tert-butylamino-2-hydroxy) propoxy-3,4-dihydrocarbostyril (OPC-1085) were compared with those of propranolol. OPC-1085 had a potency about 3 times greater than that of propranolol in blocking the positive inotropic and chronotropic effects of isoprenaline on the isolated guinea pig atrium. At a concentration of over 3 X 10(-5) M OPC-1085 produced negative inotropic and chronotropic effects. However, these effects were about 10 times weaker than those of propranolol. Suppressing effects on the rate of rise and on the maximum driving frequency of action potentials were also more than 10 times less than those of propranolol. There was almost no change in the action potential of vagus nerve after a 10 min treatment with OPC-1085 (10(-5) M), while the action potential was reduced to 60-70% with propranolol (10(-5) M).", "contents": "A comparative study of the effects of OPC-1085 and propranolol on isolated guinea pig atrium. Effects of a newly synthesized beta-blocker, 5-(3-tert-butylamino-2-hydroxy) propoxy-3,4-dihydrocarbostyril (OPC-1085) were compared with those of propranolol. OPC-1085 had a potency about 3 times greater than that of propranolol in blocking the positive inotropic and chronotropic effects of isoprenaline on the isolated guinea pig atrium. At a concentration of over 3 X 10(-5) M OPC-1085 produced negative inotropic and chronotropic effects. However, these effects were about 10 times weaker than those of propranolol. Suppressing effects on the rate of rise and on the maximum driving frequency of action potentials were also more than 10 times less than those of propranolol. There was almost no change in the action potential of vagus nerve after a 10 min treatment with OPC-1085 (10(-5) M), while the action potential was reduced to 60-70% with propranolol (10(-5) M)."}
{"id": "PMID:18630", "title": "Stimulative effects of chelating agents, 2,2'-bipyridine and 1,10-phenanthroline, on lipid peroxidation in rat liver microsomes.", "content": "Well known lipid peroxidation inhibitors, 1,10-phenanthroline and 2,2'-bipyridine, stimulated microsomal NADPH- and ascorbic acid-dependent lipid peroxidation when low concentrations of these chelating agents were added to incubation mixture. The stimulatory effects of the chelating agents on lipid peroxidation were enhanced when ferrous ion was added together with the chelating agents to the mixture at a molar ratio of 1:1. Ethylenediaminetetraacetic acid (EDTA) had no stimulatory effect on lipid peroxidation. Ferrous ion-EDTA complex increased lipid peroxidation by only 20-30%, which was lower than that obtained by addition of the same concentration of ferrous ion alone. On the other hand, manganese and calcium ions, which are also inhibitors of lipid peroxidation, had no ability to stimulate lipid peroxidation even in the presence of extra ferrous ions. Changes in the lipid peroxidation by chelating agents affected the apparent activity of ethylmorphine N-demethylation.", "contents": "Stimulative effects of chelating agents, 2,2'-bipyridine and 1,10-phenanthroline, on lipid peroxidation in rat liver microsomes. Well known lipid peroxidation inhibitors, 1,10-phenanthroline and 2,2'-bipyridine, stimulated microsomal NADPH- and ascorbic acid-dependent lipid peroxidation when low concentrations of these chelating agents were added to incubation mixture. The stimulatory effects of the chelating agents on lipid peroxidation were enhanced when ferrous ion was added together with the chelating agents to the mixture at a molar ratio of 1:1. Ethylenediaminetetraacetic acid (EDTA) had no stimulatory effect on lipid peroxidation. Ferrous ion-EDTA complex increased lipid peroxidation by only 20-30%, which was lower than that obtained by addition of the same concentration of ferrous ion alone. On the other hand, manganese and calcium ions, which are also inhibitors of lipid peroxidation, had no ability to stimulate lipid peroxidation even in the presence of extra ferrous ions. Changes in the lipid peroxidation by chelating agents affected the apparent activity of ethylmorphine N-demethylation."}
{"id": "PMID:18631", "title": "Analysis of hypotensive mechanisms of pindolol, a beta-adrenoceptor blocking drugs in rats.", "content": "The hypotensive mechanisms of pindolol in anesthetized and conscious rats were investigated. Pindolol caused a fall in blood pressure in anesthetized, conscious and spinal rats, though in conscious rats a higher dose of the drug was required to produce such a response. This hypotension with pindolol in anesthetized and conscious rats was markedly inhibited by pretreatment with the drug itself or other beta-adrenoceptor blocking drugs. A similar phenomenon also occurred when isoproterenol was injected intravenously in anesthetized and conscious rats. The relationship between the hypotensive actions of four beta-adrenoceptor blocking drugs in anesthetized rats and their intrinsic beta-sympathomimetic actions in isolated catecholamine-depleted tracheal preparations was determined. Order of hypotensive potencies was the same as that of their intrinsic beta-sympathomimetic action, namely, pindolol greater than carteolol greater than bufetolol in equilibrium propranolol (p less than 0.05). These results suggest that the hypotension with pindolol is mediated through a decrease in the peripheral vascular resistance due to an intrinsic beta-sympathomimetic action of the drug.", "contents": "Analysis of hypotensive mechanisms of pindolol, a beta-adrenoceptor blocking drugs in rats. The hypotensive mechanisms of pindolol in anesthetized and conscious rats were investigated. Pindolol caused a fall in blood pressure in anesthetized, conscious and spinal rats, though in conscious rats a higher dose of the drug was required to produce such a response. This hypotension with pindolol in anesthetized and conscious rats was markedly inhibited by pretreatment with the drug itself or other beta-adrenoceptor blocking drugs. A similar phenomenon also occurred when isoproterenol was injected intravenously in anesthetized and conscious rats. The relationship between the hypotensive actions of four beta-adrenoceptor blocking drugs in anesthetized rats and their intrinsic beta-sympathomimetic actions in isolated catecholamine-depleted tracheal preparations was determined. Order of hypotensive potencies was the same as that of their intrinsic beta-sympathomimetic action, namely, pindolol greater than carteolol greater than bufetolol in equilibrium propranolol (p less than 0.05). These results suggest that the hypotension with pindolol is mediated through a decrease in the peripheral vascular resistance due to an intrinsic beta-sympathomimetic action of the drug."}
{"id": "PMID:18635", "title": "Drug-induced dystonic reactions.", "content": "In the 12 unusual cases of drug-induced dystonic reaction discussed, major tranquilizers were ingested unaccompanied by anti-parkinsonian drugs. The five characteristics of the drug-induced dystonic reactions are oculogyric crisis, torticollic crisis, buccolingual crisis, opisthotonic crisis, and tortipelvic and gait crisis. Neuromuscular manifestations occur in the oculogyric, torticollic, buccolingual, opisthotonic and tortipelvic regions. The basic treatment is to discontinue major tranquilizers and administer anticholinergic agents to block the enhanced cholinergic function. Useful anticholinergic and antihistaminic agents for the treatment of drug-induced dystonic reactions are listed to aid in the selection of appropriate therapeutic remedies.", "contents": "Drug-induced dystonic reactions. In the 12 unusual cases of drug-induced dystonic reaction discussed, major tranquilizers were ingested unaccompanied by anti-parkinsonian drugs. The five characteristics of the drug-induced dystonic reactions are oculogyric crisis, torticollic crisis, buccolingual crisis, opisthotonic crisis, and tortipelvic and gait crisis. Neuromuscular manifestations occur in the oculogyric, torticollic, buccolingual, opisthotonic and tortipelvic regions. The basic treatment is to discontinue major tranquilizers and administer anticholinergic agents to block the enhanced cholinergic function. Useful anticholinergic and antihistaminic agents for the treatment of drug-induced dystonic reactions are listed to aid in the selection of appropriate therapeutic remedies."}
{"id": "PMID:18637", "title": "[Ocular disturbances in asthenic neurosis and their treatment (author's transl)].", "content": "The author has studied over 200 cases of asthenic neurosis. The ocular manifestations could be classified into four clinical types according to the dominant ocular symptoms. 58.34% of these patients were female and 41.66% were male. 78% of the patients were between 20 and 40 years. 59% were students. In 75% of these cases a raised retinal blood pressure as an ocular manifestation was discovered. The ocular disturbances in asthenic neurosis are present especially in persons who regularly work more than 8 hours continuously. The treatment consists of physical and intellectual rest periods, sedatives, tonics, and connective tissue therapy with extracts of whole eyeballs. In 80% of cases we had favourable results.", "contents": "[Ocular disturbances in asthenic neurosis and their treatment (author's transl)]. The author has studied over 200 cases of asthenic neurosis. The ocular manifestations could be classified into four clinical types according to the dominant ocular symptoms. 58.34% of these patients were female and 41.66% were male. 78% of the patients were between 20 and 40 years. 59% were students. In 75% of these cases a raised retinal blood pressure as an ocular manifestation was discovered. The ocular disturbances in asthenic neurosis are present especially in persons who regularly work more than 8 hours continuously. The treatment consists of physical and intellectual rest periods, sedatives, tonics, and connective tissue therapy with extracts of whole eyeballs. In 80% of cases we had favourable results."}
{"id": "PMID:18638", "title": "Plasma catecholamines in exercise induced bronchoconstriction.", "content": "Plasma nor-epinephrine (NE) and epinephrine (E) levels at rest and immediately after exercise were estimated in 8 patients with asymptomatic extrinsic allergic bronchial asthma. The patients had a normal airway resistance at rest and developed a marked bronchoconstriction (EIB) during exercise, which could be prevented by previous alpha-adrenergic blockade with phentolamine. In 7 control persons NE and E levels were measured also after beta-adrenergic blockade with propranolol. The following results were obtained: 1. At rest NE levels showed no significant differences between the groups. After exercise an increase of NE was observed in all groups, but in patients, even after phentolamine, and in normals after propranolol the increase was significantly higher than in the normal group within the control test. 2. No significant differences between the groups were found in E levels at rest and after exercise. Exercise caused no significant increase of E levels, except in the normals after propranolol application. 3. No significant correlation existed between NE levels and the increase of airway resistance after exercise. It is concluded that during exercise in asthmatics the sympathetic activity is enhanced, but the provocation of an EIB does not seem to be mediated by enhanced plasma NE levels.", "contents": "Plasma catecholamines in exercise induced bronchoconstriction. Plasma nor-epinephrine (NE) and epinephrine (E) levels at rest and immediately after exercise were estimated in 8 patients with asymptomatic extrinsic allergic bronchial asthma. The patients had a normal airway resistance at rest and developed a marked bronchoconstriction (EIB) during exercise, which could be prevented by previous alpha-adrenergic blockade with phentolamine. In 7 control persons NE and E levels were measured also after beta-adrenergic blockade with propranolol. The following results were obtained: 1. At rest NE levels showed no significant differences between the groups. After exercise an increase of NE was observed in all groups, but in patients, even after phentolamine, and in normals after propranolol the increase was significantly higher than in the normal group within the control test. 2. No significant differences between the groups were found in E levels at rest and after exercise. Exercise caused no significant increase of E levels, except in the normals after propranolol application. 3. No significant correlation existed between NE levels and the increase of airway resistance after exercise. It is concluded that during exercise in asthmatics the sympathetic activity is enhanced, but the provocation of an EIB does not seem to be mediated by enhanced plasma NE levels."}
{"id": "PMID:18640", "title": "Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases.", "content": "The clinical and morphologic findings of allergic granulomatosis and angiitis of Churg and Strauss in 21 men and 9 women were reviewed. The classic features are those of systemic vasculitis in a setting of bronchial asthma and eosinophilia. Pathologically there is necrotizing vasculitis of small arteries and veins with extravascular granulomas, and infiltration of vessels and perivascular tissues with eosinophilia. These features differentiate it from poly-arteritis nodosa. The lungs, peripheral nerves, and skin are most frequently involved. Renal failure was encountered in only one patient in this series. Shortness of the interval from onset of asthma to appearance of vasculitis is an unfavorable prognostic sign. Corticosteroids seem to influence long-term survival favorably.", "contents": "Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases. The clinical and morphologic findings of allergic granulomatosis and angiitis of Churg and Strauss in 21 men and 9 women were reviewed. The classic features are those of systemic vasculitis in a setting of bronchial asthma and eosinophilia. Pathologically there is necrotizing vasculitis of small arteries and veins with extravascular granulomas, and infiltration of vessels and perivascular tissues with eosinophilia. These features differentiate it from poly-arteritis nodosa. The lungs, peripheral nerves, and skin are most frequently involved. Renal failure was encountered in only one patient in this series. Shortness of the interval from onset of asthma to appearance of vasculitis is an unfavorable prognostic sign. Corticosteroids seem to influence long-term survival favorably."}
{"id": "PMID:18647", "title": "Interrelationship between the dietary regulation of fatty acid synthesis and the fatty acyl-CoA desaturases.", "content": "In this paper we present further evidence for the close control of fatty acid synthetase and stearoyl-CoA desaturase. Furthermore, we have established that whereas dietary palmitic acid may influence the activity of this desaturase but not of fatty acid synthetase, dietary linoleic acid appears to control both these enzymes. Finally, we have studied the influence of dietary fat and carbohydrate on the activities of the delta6 and delta5 desaturases. The former is only slightly affected by these dietary components. The delta5 desaturase activity is stimulated as the dietary fat content rises but is unaffected by dietary carbohydrate. The control of these enzymes is therefore independent of the control of fatty acid synthetase and stearoyl-CoA desaturase. From the data presented, the magnitude of the controlling effect of polyunsaturated fatty acids on fatty acid synthetase and stearoyl-CoA desaturase activity is determined and its relevance to lipogenesis in man based on daily intake of carbohydrate and linoleic acid is discussed.", "contents": "Interrelationship between the dietary regulation of fatty acid synthesis and the fatty acyl-CoA desaturases. In this paper we present further evidence for the close control of fatty acid synthetase and stearoyl-CoA desaturase. Furthermore, we have established that whereas dietary palmitic acid may influence the activity of this desaturase but not of fatty acid synthetase, dietary linoleic acid appears to control both these enzymes. Finally, we have studied the influence of dietary fat and carbohydrate on the activities of the delta6 and delta5 desaturases. The former is only slightly affected by these dietary components. The delta5 desaturase activity is stimulated as the dietary fat content rises but is unaffected by dietary carbohydrate. The control of these enzymes is therefore independent of the control of fatty acid synthetase and stearoyl-CoA desaturase. From the data presented, the magnitude of the controlling effect of polyunsaturated fatty acids on fatty acid synthetase and stearoyl-CoA desaturase activity is determined and its relevance to lipogenesis in man based on daily intake of carbohydrate and linoleic acid is discussed."}
{"id": "PMID:18648", "title": "Studies on the inhibition of the desaturases by cyclopropenoid fatty acids.", "content": "Unwashed rat liver microsomes were used to study the inhibition of the delta6 and delta9 desaturases by cyclopropenoid fatty acids with the ring structure about the 9,10 or 6,7 carbon atoms. The 9,10 cyclopropenoid acid (sterculic acid) is shown to be an effective inhibitor of only delta9 desaturase and then only in the presence of MgCl2 and coenzyme A (presumably due to the formation of sterculoyl-CoA). Two 6,7 cyclopropenoid acids of different chain lengths showed no marked inhibition of either the delta6 or delta9 desaturase. By the use of [3H]-sterculic acid, it has been shown that under conditions of high inhibition of the delta9 desaturase the inhibitor is not covalently attached to the enzyme at any point. This disproves older ideas on the mechanism of inhibition that assumed reaction between the cyclopropenoid ring and sulphydryl groups on the enzymes.", "contents": "Studies on the inhibition of the desaturases by cyclopropenoid fatty acids. Unwashed rat liver microsomes were used to study the inhibition of the delta6 and delta9 desaturases by cyclopropenoid fatty acids with the ring structure about the 9,10 or 6,7 carbon atoms. The 9,10 cyclopropenoid acid (sterculic acid) is shown to be an effective inhibitor of only delta9 desaturase and then only in the presence of MgCl2 and coenzyme A (presumably due to the formation of sterculoyl-CoA). Two 6,7 cyclopropenoid acids of different chain lengths showed no marked inhibition of either the delta6 or delta9 desaturase. By the use of [3H]-sterculic acid, it has been shown that under conditions of high inhibition of the delta9 desaturase the inhibitor is not covalently attached to the enzyme at any point. This disproves older ideas on the mechanism of inhibition that assumed reaction between the cyclopropenoid ring and sulphydryl groups on the enzymes."}
{"id": "PMID:18651", "title": "Penicillin combinations against multi-resistant urinary pathogens as an alternative to gentamycin treatment.", "content": "A total of 42 multi-resistant urinary pathogens, sensitive to gentamycin only, were investigated with regard to the effects of dicloxacillin and ampicillin or cloxacillin/flucloxacillin and amoxycillin in combination. A synergistic antibiotic effect with resulting low MIC levels was demonstrated for 81% of the strains. It was also found that a further increase in sensitivity might be achieved by adjustment of the pH level.", "contents": "Penicillin combinations against multi-resistant urinary pathogens as an alternative to gentamycin treatment. A total of 42 multi-resistant urinary pathogens, sensitive to gentamycin only, were investigated with regard to the effects of dicloxacillin and ampicillin or cloxacillin/flucloxacillin and amoxycillin in combination. A synergistic antibiotic effect with resulting low MIC levels was demonstrated for 81% of the strains. It was also found that a further increase in sensitivity might be achieved by adjustment of the pH level."}
{"id": "PMID:18652", "title": "Pathway of glucose catabolism in Caulobacter crescentus.", "content": "Glucose when present as a sole organic carbon source in a mineral salts medium is dissimilated by Caulobacter crescentus ATCC 15252 (strain CB-2) by the Entner-Doudoroff pathway throughout the culture cycle (exponential, transition, and stationary phase). Most of the available glucose that is present at the onset of exponential growth is assimilated by the cells during the transition phase or the period associated with stalk cell development. Swarmer cell development is minimized during this phase. During this same period the pH drops from 6.1 to 4.9 as a result of an abundant excretion of acetic acid. Simultaneously, poly-beta-hydroxybutyrate accumulates within the cells at an accelerated rate. An NADP-dependent glyceraldehyde-3-phosphate dehydrogenase is also present throughout the culture cycle which subsumes the presence of the subsequent enzymes of the Embden-Meyerhof-Parnas pathway in pyruvate formation. An operative tricarboxylic acid cycle is associated with cells throughout the culture cycle.", "contents": "Pathway of glucose catabolism in Caulobacter crescentus. Glucose when present as a sole organic carbon source in a mineral salts medium is dissimilated by Caulobacter crescentus ATCC 15252 (strain CB-2) by the Entner-Doudoroff pathway throughout the culture cycle (exponential, transition, and stationary phase). Most of the available glucose that is present at the onset of exponential growth is assimilated by the cells during the transition phase or the period associated with stalk cell development. Swarmer cell development is minimized during this phase. During this same period the pH drops from 6.1 to 4.9 as a result of an abundant excretion of acetic acid. Simultaneously, poly-beta-hydroxybutyrate accumulates within the cells at an accelerated rate. An NADP-dependent glyceraldehyde-3-phosphate dehydrogenase is also present throughout the culture cycle which subsumes the presence of the subsequent enzymes of the Embden-Meyerhof-Parnas pathway in pyruvate formation. An operative tricarboxylic acid cycle is associated with cells throughout the culture cycle."}
{"id": "PMID:18656", "title": "Changes in blood pressure and antihypertensive treatment in a community over four years.", "content": "In 1971 persons aged 50 to 59 years in Albury were screened for hypertension and those with diastolic blood pressure equal to or over 110 mm Hg were notified. On screening of the sample in 1975, the proportion of persons receiving treatment had doubled to 22%. Most of those newly receiving treatment in 1975 had had diastolic blood pressures under 110 mm Hg in 1971. The mean systolic and diastolic pressures of the newly treated group had fallen by 13-7 and 9-1 mm Hg respectively to 153-5 and 91-6 mm Hg. The mean pressures of subjects already receiving treatment in 1971 and continuing it remained higher (163-1 mm Hg systolic and 100-9 mm Hg diastolic), despite their receiving relatively more medication. The latter group was composed of patients likely to have had more severe hypertension originally, and the importance of effective treatment for them is emphasized. The frequency with which subjects with mild hypertension are being treated demonstrates the urgent need to complete randomized controlled trials of treatment in this group.", "contents": "Changes in blood pressure and antihypertensive treatment in a community over four years. In 1971 persons aged 50 to 59 years in Albury were screened for hypertension and those with diastolic blood pressure equal to or over 110 mm Hg were notified. On screening of the sample in 1975, the proportion of persons receiving treatment had doubled to 22%. Most of those newly receiving treatment in 1975 had had diastolic blood pressures under 110 mm Hg in 1971. The mean systolic and diastolic pressures of the newly treated group had fallen by 13-7 and 9-1 mm Hg respectively to 153-5 and 91-6 mm Hg. The mean pressures of subjects already receiving treatment in 1971 and continuing it remained higher (163-1 mm Hg systolic and 100-9 mm Hg diastolic), despite their receiving relatively more medication. The latter group was composed of patients likely to have had more severe hypertension originally, and the importance of effective treatment for them is emphasized. The frequency with which subjects with mild hypertension are being treated demonstrates the urgent need to complete randomized controlled trials of treatment in this group."}
{"id": "PMID:18653", "title": "[Influence of amino acids on synthesis of extracellular proteases by Actinomyces thermovulgaris].", "content": "Various amino acids had different effect on the synthesis of exocellular proteases by Actinomyces thermovulgaris T-54. Glutamine and arginine induced the synthesis, the effect depending on their concentration in the medium. Other amino acids inhibited the synthesis of proteases. The synthesis of alkaline and neutral proteases was not coordinated, and the ratio between these enzymes was not constant in different variants of the experiment. The maximum synthesis of alkaline proteases was found before the formation of submerged spores.", "contents": "[Influence of amino acids on synthesis of extracellular proteases by Actinomyces thermovulgaris]. Various amino acids had different effect on the synthesis of exocellular proteases by Actinomyces thermovulgaris T-54. Glutamine and arginine induced the synthesis, the effect depending on their concentration in the medium. Other amino acids inhibited the synthesis of proteases. The synthesis of alkaline and neutral proteases was not coordinated, and the ratio between these enzymes was not constant in different variants of the experiment. The maximum synthesis of alkaline proteases was found before the formation of submerged spores."}
{"id": "PMID:18658", "title": "A comparison of the genetic and physical size of the streptomycin resistance locus in Pneumococcus.", "content": "Polyacrylamide gel electrophoresis of the 30S ribosomal proteins derived from six streptomycin resistant strains indicates that each mutation alters the same ribosomal protein (str-r protein). Preliminary data utilizing SDS gels indicates that the str-r protein has a molecular weight between 10,000 and 20,000 daltons. No significant differences could be detected between the molecular weight of the str-r protein when it is derived either from a sensitive or from a resistant strain, including those derived from strains carrying multisite mutations of different genetic size. We have estimated the size of the multisite str-r mutations to be less than 30 base pairs. Two factor crosses with str-r markers in the trans position demonstrate recombination frequencies expected of closely linked, intragenic markers although cotransfer frequencies, of these same markers from the cis position, are very low. It is concluded that the cotransfer frequencies represent a marker effect and possible explanations are discussed. A reinterpretation of the genetic map of the pneumococcal str-r locus is presented.", "contents": "A comparison of the genetic and physical size of the streptomycin resistance locus in Pneumococcus. Polyacrylamide gel electrophoresis of the 30S ribosomal proteins derived from six streptomycin resistant strains indicates that each mutation alters the same ribosomal protein (str-r protein). Preliminary data utilizing SDS gels indicates that the str-r protein has a molecular weight between 10,000 and 20,000 daltons. No significant differences could be detected between the molecular weight of the str-r protein when it is derived either from a sensitive or from a resistant strain, including those derived from strains carrying multisite mutations of different genetic size. We have estimated the size of the multisite str-r mutations to be less than 30 base pairs. Two factor crosses with str-r markers in the trans position demonstrate recombination frequencies expected of closely linked, intragenic markers although cotransfer frequencies, of these same markers from the cis position, are very low. It is concluded that the cotransfer frequencies represent a marker effect and possible explanations are discussed. A reinterpretation of the genetic map of the pneumococcal str-r locus is presented."}
{"id": "PMID:18655", "title": "[Ecologic features of cultures of the species Clostridium g\u00fcrfelii].", "content": "The Clostridium cultures decomposing pectin were isolated from flax straw during flax retting. The activity was manifested only at high pH values, the optimum pH being 6.7--8.2. Such ecological adaptation of the cultures is determined by the properties of the pectolytic enzyme complex which they synthesize. The complex does not contained polygalacturonase (the optimum pH 5.0) but has a high activity of pectate transeliminase (the optimum pH 8.0--8.4). The cultures differ from Clostridium felsineum which possesses a high activity of polygalacturonase and therefore can decompose pectin in acid medium. By their morphological, cultural and physiological properties, the bacteria are classed as Clostridium g\u00fcfelii (Pr\u00e9vot, 1966).", "contents": "[Ecologic features of cultures of the species Clostridium g\u00fcrfelii]. The Clostridium cultures decomposing pectin were isolated from flax straw during flax retting. The activity was manifested only at high pH values, the optimum pH being 6.7--8.2. Such ecological adaptation of the cultures is determined by the properties of the pectolytic enzyme complex which they synthesize. The complex does not contained polygalacturonase (the optimum pH 5.0) but has a high activity of pectate transeliminase (the optimum pH 8.0--8.4). The cultures differ from Clostridium felsineum which possesses a high activity of polygalacturonase and therefore can decompose pectin in acid medium. By their morphological, cultural and physiological properties, the bacteria are classed as Clostridium g\u00fcfelii (Pr\u00e9vot, 1966)."}
{"id": "PMID:18664", "title": "Organization of purpine degradation in the liver of a teleost (carp; Cyprinus carpio L.). A study of its subcellular distribution.", "content": "Carp liver was fractionated by differential and density gradient centrifugation and assayed for enzymes of purine catabolism. While urate oxidase is an exclusively peroxisomal enzyme, only a very small percentage of the enzymes xanthine oxidase, allantoinase and allantoicase is associated with subcellular or ganelle fractions. There is no general purine catabolizing subcellular compartment. There is some but not yet conclusive evidence for the assumption that urate oxidase is a membrane bound enzyme.", "contents": "Organization of purpine degradation in the liver of a teleost (carp; Cyprinus carpio L.). A study of its subcellular distribution. Carp liver was fractionated by differential and density gradient centrifugation and assayed for enzymes of purine catabolism. While urate oxidase is an exclusively peroxisomal enzyme, only a very small percentage of the enzymes xanthine oxidase, allantoinase and allantoicase is associated with subcellular or ganelle fractions. There is no general purine catabolizing subcellular compartment. There is some but not yet conclusive evidence for the assumption that urate oxidase is a membrane bound enzyme."}
{"id": "PMID:18665", "title": "Enzymatic synthesis of polyprenol monophosphate mannose in insects.", "content": "The microsomal fraction of insects was found to contain an enzyme which transfers mannose from guanosine diphosphate mannose to an endogenous or exogenous insect lipid and to other acceptors such as dolichol monophosphate or ficaprenol monophosphate. This activity depended on the presence of Triton X-100 and magnesium ions, the optimal concentration of the latter being 10mM. The optimal temperature of the reaction was 25 degrees C and the maximal activity was obtained at pH 7.9. The mannolipid formed behaved as a monophosphodiester when chromatographed on DEAE-cellulose. Weak acid treatment of the product liberated mannose. Its behaviour both on thin layer and Sephadex G-150 chromatography would indicate the presence of a number of isoprenyl units similar to the dolichol and different from the ficaprenol derivative. Stability to phenol treatment indicated that the lipid fraction of the mannolipid is an alpha-saturated polyprenol phosphate similar to dolichol monophosphate.", "contents": "Enzymatic synthesis of polyprenol monophosphate mannose in insects. The microsomal fraction of insects was found to contain an enzyme which transfers mannose from guanosine diphosphate mannose to an endogenous or exogenous insect lipid and to other acceptors such as dolichol monophosphate or ficaprenol monophosphate. This activity depended on the presence of Triton X-100 and magnesium ions, the optimal concentration of the latter being 10mM. The optimal temperature of the reaction was 25 degrees C and the maximal activity was obtained at pH 7.9. The mannolipid formed behaved as a monophosphodiester when chromatographed on DEAE-cellulose. Weak acid treatment of the product liberated mannose. Its behaviour both on thin layer and Sephadex G-150 chromatography would indicate the presence of a number of isoprenyl units similar to the dolichol and different from the ficaprenol derivative. Stability to phenol treatment indicated that the lipid fraction of the mannolipid is an alpha-saturated polyprenol phosphate similar to dolichol monophosphate."}
{"id": "PMID:18666", "title": "A primer independent activity of rabbit muscle phosphorylase b.", "content": "Rabbit muscle phosphorylase b was found to be capable of forming protein bound alpha-1,4 glucosyl chains upon incubation of the enzyme with appropriate concentrations of glucose-1-phosphate with no primer addition (unprimed synthesis). This activity would only be present in a small fraction of the total muscle phosphorylase b activity, as judged from the high concentrations of enzyme which are required to demonstrate the occurrence of unprimed synthesis. Polyacrylamide gel electrophoresis shows the presence of a phosphorylase isoenzyme capable of accepting glucosyl moieties, giving rise to a glucosylated protein enzymatically active in the chain lengthening of its own glucan.", "contents": "A primer independent activity of rabbit muscle phosphorylase b. Rabbit muscle phosphorylase b was found to be capable of forming protein bound alpha-1,4 glucosyl chains upon incubation of the enzyme with appropriate concentrations of glucose-1-phosphate with no primer addition (unprimed synthesis). This activity would only be present in a small fraction of the total muscle phosphorylase b activity, as judged from the high concentrations of enzyme which are required to demonstrate the occurrence of unprimed synthesis. Polyacrylamide gel electrophoresis shows the presence of a phosphorylase isoenzyme capable of accepting glucosyl moieties, giving rise to a glucosylated protein enzymatically active in the chain lengthening of its own glucan."}
{"id": "PMID:18667", "title": "Sucrose metabolism in green algae. I. The presence of sucrose synthetase and sucrose phosphate synthetase.", "content": "The presence of sucrose synthetase and sucrose phosphate synthetase has been demonstrated in two species of green algae: Chlorella vulgaris and Scenedesmus obliquus. Partial purification from crude extracts allowed the determination of the kinetic constants of algae enzymes. They are very similar to the ones reported for enzymes from higher plants.", "contents": "Sucrose metabolism in green algae. I. The presence of sucrose synthetase and sucrose phosphate synthetase. The presence of sucrose synthetase and sucrose phosphate synthetase has been demonstrated in two species of green algae: Chlorella vulgaris and Scenedesmus obliquus. Partial purification from crude extracts allowed the determination of the kinetic constants of algae enzymes. They are very similar to the ones reported for enzymes from higher plants."}
{"id": "PMID:18668", "title": "Trisialoganglioside synthesis by a chicken brain sialyltransferase. Comparative study with the similar reaction for the synthesis of disialoganglioside.", "content": "An enzyme preparation from embryonic chicken brain catalyzes the transfer of sialic acid from CMP-N-acetylneuraminic acid to ceramide-Glc-Gal(NeuAc-NeuAc)-GalNAc-Gal (GDlb) to form ceramide-Glc-Gal(NeuAc-NeuAc)-GalNAc-Gal-NeuAc (GTlb). The sialyltransferase activity was measured during the development of the embryo, the subcellular distribution of this activity was determined and several kinetic properties of the reaction were examined. A comparative study with the similar reaction involved in the transfer of sialic acid to the terminal galactose in ceramide-Glc-Gal(NeuAc)-GalNAc-Gal (GMl) was made. The results obtained in this comparative study suggest that the transfer of sialic acid in both reactions is catalyzed by the same enzyme.", "contents": "Trisialoganglioside synthesis by a chicken brain sialyltransferase. Comparative study with the similar reaction for the synthesis of disialoganglioside. An enzyme preparation from embryonic chicken brain catalyzes the transfer of sialic acid from CMP-N-acetylneuraminic acid to ceramide-Glc-Gal(NeuAc-NeuAc)-GalNAc-Gal (GDlb) to form ceramide-Glc-Gal(NeuAc-NeuAc)-GalNAc-Gal-NeuAc (GTlb). The sialyltransferase activity was measured during the development of the embryo, the subcellular distribution of this activity was determined and several kinetic properties of the reaction were examined. A comparative study with the similar reaction involved in the transfer of sialic acid to the terminal galactose in ceramide-Glc-Gal(NeuAc)-GalNAc-Gal (GMl) was made. The results obtained in this comparative study suggest that the transfer of sialic acid in both reactions is catalyzed by the same enzyme."}
{"id": "PMID:18669", "title": "Porphyrin biosynthesis. Immobilized enzymes. IV. Studies on aminolaevulate dehydratase attached to Sepharose.", "content": "Bovine liver aminolaevulate dehydratase (ALA-D) has been chemically attached to Sepharose 4B and its properties have been studied. The optimal conditions for coupling have been determined. It was found that the immobilized enzyme retained a significant percentage of the activity of the free enzyme. The coupling yield was rather high. The insolubilized enzyme requires both anaerobiosis and a thiol activator for maximal activity. It can be stored at 4 degrees C for long periods with little loss of activity and it can be repeatedly used without alteration of its enzymic capacity. Attachment of ALA-D to the gel has led to an enhanced thermal stability. pH optima of free and bound enzyme was the same while a small decrease in the Km of the matrix bonded ALA-D as compared to that of the soluble enzyme was observed. The use of the fixed-ALA-D for the preparation of PBG is described.", "contents": "Porphyrin biosynthesis. Immobilized enzymes. IV. Studies on aminolaevulate dehydratase attached to Sepharose. Bovine liver aminolaevulate dehydratase (ALA-D) has been chemically attached to Sepharose 4B and its properties have been studied. The optimal conditions for coupling have been determined. It was found that the immobilized enzyme retained a significant percentage of the activity of the free enzyme. The coupling yield was rather high. The insolubilized enzyme requires both anaerobiosis and a thiol activator for maximal activity. It can be stored at 4 degrees C for long periods with little loss of activity and it can be repeatedly used without alteration of its enzymic capacity. Attachment of ALA-D to the gel has led to an enhanced thermal stability. pH optima of free and bound enzyme was the same while a small decrease in the Km of the matrix bonded ALA-D as compared to that of the soluble enzyme was observed. The use of the fixed-ALA-D for the preparation of PBG is described."}
{"id": "PMID:18670", "title": "[Complications of pertussis immunization (author transl)].", "content": "16 cases of neurological disease and/or death shortly after pertussis immunization are reported. Eight patients had convulsions, six with ensuing permanent defects. Severe polymyositis was observed in one case. Five infants died 12 h to 4 days after vaccination: two after acute encephalopathy and three in the form of a sudden unexpected death (SID). In two fatal cases the morphological changes in the brain corresponded to those of pertussis encephalopathy: neuronal degeneration in various parts of the cortex, especially in the region of the ammons horn, and in the cerebellum. There were no signs of inflammation. Three cases underwent forensic autopsy and death was attributed to bronchopulmonary infection. Complete neuropathological work-up was only done in one case, in which the brain was normal. The critique of episodical reports and the demand for prospective studies is appreciated. Knowledge of all possible forms of complications, however, is indispensable for future investigations. Polymyositis and SID have so far not been listed as abnormal reactions to immunization. The majority of our cases became known accidentally from hospital sheets or from discussions with collegues. For a detection of all possible cases a greater awareness of doctors for the problem of pertussis immunization appears necessary. Only another 23 cases have been reported to the health authorities of the state of Lower Saxony during the last 6 to 7 years. Of those, nine were either harmless reactions or diseases probably unrelated to vaccination. Two were cases of SID, 12 and 72 h after vaccination. It is concluded that only a minor proportion of possible complications is presently reported to the health authorities.", "contents": "[Complications of pertussis immunization (author transl)]. 16 cases of neurological disease and/or death shortly after pertussis immunization are reported. Eight patients had convulsions, six with ensuing permanent defects. Severe polymyositis was observed in one case. Five infants died 12 h to 4 days after vaccination: two after acute encephalopathy and three in the form of a sudden unexpected death (SID). In two fatal cases the morphological changes in the brain corresponded to those of pertussis encephalopathy: neuronal degeneration in various parts of the cortex, especially in the region of the ammons horn, and in the cerebellum. There were no signs of inflammation. Three cases underwent forensic autopsy and death was attributed to bronchopulmonary infection. Complete neuropathological work-up was only done in one case, in which the brain was normal. The critique of episodical reports and the demand for prospective studies is appreciated. Knowledge of all possible forms of complications, however, is indispensable for future investigations. Polymyositis and SID have so far not been listed as abnormal reactions to immunization. The majority of our cases became known accidentally from hospital sheets or from discussions with collegues. For a detection of all possible cases a greater awareness of doctors for the problem of pertussis immunization appears necessary. Only another 23 cases have been reported to the health authorities of the state of Lower Saxony during the last 6 to 7 years. Of those, nine were either harmless reactions or diseases probably unrelated to vaccination. Two were cases of SID, 12 and 72 h after vaccination. It is concluded that only a minor proportion of possible complications is presently reported to the health authorities."}
{"id": "PMID:18672", "title": "Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism.", "content": "In four patients with renal hyperchloremic acidosis and hyperkalemia, hyporeninemic hypoaldosteronism and chronic renal insufficiency (glomerular filtration rates of 13, 31, 35 and 44 ml per minute per 1.73 m2), prolonged administration of fludrocortisone increased urinary potassium and net acid excretion, corrected hyperkalemia and substantially ameliorated acidosis. Except in the patient with the lowest glomerular filtration rate, the increased net acid excretion was due mostly to increased ammonium excretion. Urine pH decreased initially in each patient, but in the three patients with the highest filtration rates, it increased subsequently as ammonium excretion increased, indicating that renal ammonia production increased. Urinary ammonium excretion correlated inversely with serum potassium concentration and did not decrease on discontinuation of therapy if hyperkalemia was prevented from recurring. In patients with renal acidosis and hyporeninemic hypoaldosteronism, administration of mineralocorticoid hormone can augment both renal hydrogen-ion secretion and, by correction of hyperkalemia, renal ammonia production, and thereby ameliorate metabolic acidosis.", "contents": "Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism. In four patients with renal hyperchloremic acidosis and hyperkalemia, hyporeninemic hypoaldosteronism and chronic renal insufficiency (glomerular filtration rates of 13, 31, 35 and 44 ml per minute per 1.73 m2), prolonged administration of fludrocortisone increased urinary potassium and net acid excretion, corrected hyperkalemia and substantially ameliorated acidosis. Except in the patient with the lowest glomerular filtration rate, the increased net acid excretion was due mostly to increased ammonium excretion. Urine pH decreased initially in each patient, but in the three patients with the highest filtration rates, it increased subsequently as ammonium excretion increased, indicating that renal ammonia production increased. Urinary ammonium excretion correlated inversely with serum potassium concentration and did not decrease on discontinuation of therapy if hyperkalemia was prevented from recurring. In patients with renal acidosis and hyporeninemic hypoaldosteronism, administration of mineralocorticoid hormone can augment both renal hydrogen-ion secretion and, by correction of hyperkalemia, renal ammonia production, and thereby ameliorate metabolic acidosis."}
{"id": "PMID:18682", "title": "The scientific foundations of clinical enzymology.", "content": "Clinical enzymology is the study of the activity and properties of enzymes in specimens (usually of blood) taken from patients, as an aid to the diagnosis and understanding of disease. Research in many areas of enzymology is undertaken to strengthen the foundations on which the clinical interpretation of such enzyme measurements rests. Some aspects of this research are briefly described.", "contents": "The scientific foundations of clinical enzymology. Clinical enzymology is the study of the activity and properties of enzymes in specimens (usually of blood) taken from patients, as an aid to the diagnosis and understanding of disease. Research in many areas of enzymology is undertaken to strengthen the foundations on which the clinical interpretation of such enzyme measurements rests. Some aspects of this research are briefly described."}
{"id": "PMID:18683", "title": "Modification of actins by phallotoxins.", "content": "Phallotoxins bind to filamentous actin (F-actin) from liver or rabbit muscle with Kdiss approximately 10(-8) M. By this combination the structure of F-actin is stabilized to such an extent that it will be resistant to the depolymerizing action of 0.6 M KI and of deoxyribonuclease I, to denaturation by heat (70 degrees C), and to local ruptures caused by ultrasonication or by cytochalasin B. The structural features of phallotoxins essential for affinity to F-actin are specific.", "contents": "Modification of actins by phallotoxins. Phallotoxins bind to filamentous actin (F-actin) from liver or rabbit muscle with Kdiss approximately 10(-8) M. By this combination the structure of F-actin is stabilized to such an extent that it will be resistant to the depolymerizing action of 0.6 M KI and of deoxyribonuclease I, to denaturation by heat (70 degrees C), and to local ruptures caused by ultrasonication or by cytochalasin B. The structural features of phallotoxins essential for affinity to F-actin are specific."}
{"id": "PMID:18684", "title": "Characteristics of chick cerebral beta-adrenoceptors assessed by cyclic adenosine 3',5' monophosphate formation and [3H]-propranolol binding.", "content": "Chick cerebral beta-adrenoceptors have been characterised by measurement of cyclic AMP accumulation in brain slices and assessment of the specific binding of [3H]-propranolol to cerebral membranes. The binding of [3H]-propranolol was inhibited by beta-adrenoceptor agonists and antagonists with affinities that correlated well with their ability to stimulate cyclic AMP formation or to antagonise the cyclic nucleotide accumulation induced by isoprenaline. The relative potencies of a number of drugs in several cerebral regions suggests that the receptors may be of the beta2 subtype. Regional distribution studies revealed the highest density of binding sites in the cerebellum and lowest in the optic lobes. However, the concentration of [3H]-propranolol that produced half-maximal specific binding was similar in all regions. Subcellular fractionation of cerebral hemisphere tissue demonstrated an enrichment of [3H]-propranolol binding sites in the synaptosomal and microsomal fractions. There are discrepancies between the topographical distribution of beta-adrenoceptor binding sites and the endogenous noradrenaline level in chick brain and between the number of binding sites and the intrinsic activity of beta-adrenoceptor mediated cyclic AMP formation.", "contents": "Characteristics of chick cerebral beta-adrenoceptors assessed by cyclic adenosine 3',5' monophosphate formation and [3H]-propranolol binding. Chick cerebral beta-adrenoceptors have been characterised by measurement of cyclic AMP accumulation in brain slices and assessment of the specific binding of [3H]-propranolol to cerebral membranes. The binding of [3H]-propranolol was inhibited by beta-adrenoceptor agonists and antagonists with affinities that correlated well with their ability to stimulate cyclic AMP formation or to antagonise the cyclic nucleotide accumulation induced by isoprenaline. The relative potencies of a number of drugs in several cerebral regions suggests that the receptors may be of the beta2 subtype. Regional distribution studies revealed the highest density of binding sites in the cerebellum and lowest in the optic lobes. However, the concentration of [3H]-propranolol that produced half-maximal specific binding was similar in all regions. Subcellular fractionation of cerebral hemisphere tissue demonstrated an enrichment of [3H]-propranolol binding sites in the synaptosomal and microsomal fractions. There are discrepancies between the topographical distribution of beta-adrenoceptor binding sites and the endogenous noradrenaline level in chick brain and between the number of binding sites and the intrinsic activity of beta-adrenoceptor mediated cyclic AMP formation."}
{"id": "PMID:18686", "title": "On the optimal dosage of Pro-Leu-Gly-NH2 (MIF) in neuropharmacological tests and clinical use.", "content": "Pro-Leu-Gly-NH2 (MIF) inhibits the tremor induced by oxotremorine. Objective measurement of this tremor permits the drawing of a dose-effect curve. The inhibitory effect of the peptide increases linearly with increasing doses until an optimum is reached (between 30 and 40 mg/kg i.p.). At still higher doses the peptide is inactive. The same phenomenon is observed with analogues of MIF. This finding may have important bearings on the interpretation of clinical and experimental data obtained with MIF.", "contents": "On the optimal dosage of Pro-Leu-Gly-NH2 (MIF) in neuropharmacological tests and clinical use. Pro-Leu-Gly-NH2 (MIF) inhibits the tremor induced by oxotremorine. Objective measurement of this tremor permits the drawing of a dose-effect curve. The inhibitory effect of the peptide increases linearly with increasing doses until an optimum is reached (between 30 and 40 mg/kg i.p.). At still higher doses the peptide is inactive. The same phenomenon is observed with analogues of MIF. This finding may have important bearings on the interpretation of clinical and experimental data obtained with MIF."}
{"id": "PMID:18689", "title": "[Use of an anxiolytic agent (lorazepam) in low doses in the treatment of anxiety states].", "content": "A nonblind clinical study was carried out by administering Lorazepam at a low dosage to patients with a light to moderate state of reactive anxiety. The drug was shown to be effective in the management of the target symptoms studied: anorexia, sleep induction, rhythm, and duration disturbances, depression, irritability and moodiness, fatigue, anxiety and tension, somatic anxiety, social adaptation. The results obtained are practically identical to those reported in the literature for higher doses. Moreover, low-dose Lorazepam was well tolerated and without undesired side-effects.", "contents": "[Use of an anxiolytic agent (lorazepam) in low doses in the treatment of anxiety states]. A nonblind clinical study was carried out by administering Lorazepam at a low dosage to patients with a light to moderate state of reactive anxiety. The drug was shown to be effective in the management of the target symptoms studied: anorexia, sleep induction, rhythm, and duration disturbances, depression, irritability and moodiness, fatigue, anxiety and tension, somatic anxiety, social adaptation. The results obtained are practically identical to those reported in the literature for higher doses. Moreover, low-dose Lorazepam was well tolerated and without undesired side-effects."}
{"id": "PMID:18698", "title": "Injuries to the ankle and foot in athletics.", "content": "Accurate diagnosis in ligament and ligament-bone injuries of the foot and ankle demands a knowledge of the anatomy and mechanics of the foot and ankle, a good history of the mechanism of injury, clinical examination including fingertip palpation and assessment of stability, and adequate x-ray studies, perferably in the deformed position, with stress films and arthrograms in selected cases. By making an accurate diagnosis, early proper treatment is instituted, the athlete is restored to health sooner, and, almost as important, the athlete and the coach get a more realistic prognosis regarding the end result and duration of disability.", "contents": "Injuries to the ankle and foot in athletics. Accurate diagnosis in ligament and ligament-bone injuries of the foot and ankle demands a knowledge of the anatomy and mechanics of the foot and ankle, a good history of the mechanism of injury, clinical examination including fingertip palpation and assessment of stability, and adequate x-ray studies, perferably in the deformed position, with stress films and arthrograms in selected cases. By making an accurate diagnosis, early proper treatment is instituted, the athlete is restored to health sooner, and, almost as important, the athlete and the coach get a more realistic prognosis regarding the end result and duration of disability."}
{"id": "PMID:18701", "title": "Polyarteritis nodosa in older children.", "content": "Polyarteritis in the older child is thought to be a rare disease. This study describes 11 children, 3 to 12 years of age, with polyarteritis seen over a five-year period. Fever, abdominal pain, hypertension, and leukocytosis were found in almost all. Renal disease occurred in eight. Examination of muscle, gut, or kidney tissue was an effective means of diagnosis. The pathological changes were the same as those seen in adults. There seemed to be an association between polyarteritis and group A streptococcal infection. Ten patients had a salutary response to high-dose prednisone administration.", "contents": "Polyarteritis nodosa in older children. Polyarteritis in the older child is thought to be a rare disease. This study describes 11 children, 3 to 12 years of age, with polyarteritis seen over a five-year period. Fever, abdominal pain, hypertension, and leukocytosis were found in almost all. Renal disease occurred in eight. Examination of muscle, gut, or kidney tissue was an effective means of diagnosis. The pathological changes were the same as those seen in adults. There seemed to be an association between polyarteritis and group A streptococcal infection. Ten patients had a salutary response to high-dose prednisone administration."}
{"id": "PMID:18703", "title": "Properties of the HCO-3-stimulated Mg2+ -ATPase activity in red cell membranes.", "content": "The HCO-3-stimulated Mg2+ -ATPase activity in red cell ghost fragments was investigated. Increasing the HCO-3 concentration in the incubation medium resulted in increased ATPase activity. NaHCO3 appeared to be more effective than KHCO3 in this regard. The ATPase activities were slightly stimulated by increases in ionic strength and utilized ITP almost as readily as ATP. A Mg/ATP ratio of 1.0 and a pH of 7.6 yielded maximum activity. These properties are of interest since the present enzyme is the only unquestionable instance where a HCO-3 ATPase is located in the surface membrane of a cell.", "contents": "Properties of the HCO-3-stimulated Mg2+ -ATPase activity in red cell membranes. The HCO-3-stimulated Mg2+ -ATPase activity in red cell ghost fragments was investigated. Increasing the HCO-3 concentration in the incubation medium resulted in increased ATPase activity. NaHCO3 appeared to be more effective than KHCO3 in this regard. The ATPase activities were slightly stimulated by increases in ionic strength and utilized ITP almost as readily as ATP. A Mg/ATP ratio of 1.0 and a pH of 7.6 yielded maximum activity. These properties are of interest since the present enzyme is the only unquestionable instance where a HCO-3 ATPase is located in the surface membrane of a cell."}
{"id": "PMID:18728", "title": "Methylprednisolone pulse therapy in the treatment of polyarteritis nodosa.", "content": "Two cases of lung granulomata associated with \"crescentic\" glomerulonephritis both in a clinical setting of polyarteritis nodosa were treated with high doses of intravenous methylprednisolone (\"pulse therapy\") in single injections of 30 mg/kg body-weight. In the first case rapidly progressive glomerulonephritis with 100% crescents was arrested and followed by improvement of renal function from a creatinine clearance of 5 ml/min to 30 ml/min; in the second case multiple lung granulomata of 8 months' standing, unresponsive to oral steroids, disappeared 8 days after treatment with high dosage intravenous methylprednisolone. The use of \"pulse therapy\" with methylprednisolone is advocated, not only in such cases where arteritis is known or suspected, but also in radidly progressive glomerulonephritis associated with crescents.", "contents": "Methylprednisolone pulse therapy in the treatment of polyarteritis nodosa. Two cases of lung granulomata associated with \"crescentic\" glomerulonephritis both in a clinical setting of polyarteritis nodosa were treated with high doses of intravenous methylprednisolone (\"pulse therapy\") in single injections of 30 mg/kg body-weight. In the first case rapidly progressive glomerulonephritis with 100% crescents was arrested and followed by improvement of renal function from a creatinine clearance of 5 ml/min to 30 ml/min; in the second case multiple lung granulomata of 8 months' standing, unresponsive to oral steroids, disappeared 8 days after treatment with high dosage intravenous methylprednisolone. The use of \"pulse therapy\" with methylprednisolone is advocated, not only in such cases where arteritis is known or suspected, but also in radidly progressive glomerulonephritis associated with crescents."}
{"id": "PMID:18734", "title": "Cryoenzymology in mixed solvents without cosolvent effects on enzyme specific activity.", "content": "Water-soluble polyelectrolytes in interaction with proteins are described. These polyelectrolytes make it possible to investigate enzyme-catalyzed reactions in cooled mixed solvents without the usual effects of their organic solvent component  on enzyme specific activity. The applicability of techniques developed is illustrated by results obtained on several systems. The possibility of an electrostatic \"sorting out\" of solvents and its potentialities in cryoenzymology are discussed.", "contents": "Cryoenzymology in mixed solvents without cosolvent effects on enzyme specific activity. Water-soluble polyelectrolytes in interaction with proteins are described. These polyelectrolytes make it possible to investigate enzyme-catalyzed reactions in cooled mixed solvents without the usual effects of their organic solvent component  on enzyme specific activity. The applicability of techniques developed is illustrated by results obtained on several systems. The possibility of an electrostatic \"sorting out\" of solvents and its potentialities in cryoenzymology are discussed."}
{"id": "PMID:18735", "title": "A role for asparaginyl-tRNA in the regulation of asparagine synthetase in a mammalian cell line.", "content": "The expression of asparagine synthetase activity [L-aspartate:ammonia ligase (AMP-forming), EC 6.3.1.1] in cultured Chinese hamster ovary (CHO) cells is regulated by asparagine. After transfer of CHO cells from an asparagine-supplemented medium to a medium lacking asparagine, activity increases 1.5- to 2-fold. If asparagine is added back to the medium, activity returns to control levels. To test the possible involvement of Asn-tRNAAsn in regulating the levels of asparagine synthetase, we have examined the levels of asparagine synthetase in a mutant of CHO cells containing a temperature-sensitive asparaginyl-tRNA synthetase [L-asparagine:tRNA ligase (AMP-forming), EC 6.1.1.22]. Under conditions of limited asparaginyl-tRNA synthetase activity in the mutant, there is a 2- to 3-fold increase in the level of asparagine synthetase activity. Under identical conditions, there is no change in asparagine synthetase activity in the wild type. This correlation between asparaginyl-tRNA synthetase activity and asparagine synthetase levels may be a consequence of a direct role of tRNAAsn in the regulation of the in vivo expression of the asparagine synthetase structural gene.", "contents": "A role for asparaginyl-tRNA in the regulation of asparagine synthetase in a mammalian cell line. The expression of asparagine synthetase activity [L-aspartate:ammonia ligase (AMP-forming), EC 6.3.1.1] in cultured Chinese hamster ovary (CHO) cells is regulated by asparagine. After transfer of CHO cells from an asparagine-supplemented medium to a medium lacking asparagine, activity increases 1.5- to 2-fold. If asparagine is added back to the medium, activity returns to control levels. To test the possible involvement of Asn-tRNAAsn in regulating the levels of asparagine synthetase, we have examined the levels of asparagine synthetase in a mutant of CHO cells containing a temperature-sensitive asparaginyl-tRNA synthetase [L-asparagine:tRNA ligase (AMP-forming), EC 6.1.1.22]. Under conditions of limited asparaginyl-tRNA synthetase activity in the mutant, there is a 2- to 3-fold increase in the level of asparagine synthetase activity. Under identical conditions, there is no change in asparagine synthetase activity in the wild type. This correlation between asparaginyl-tRNA synthetase activity and asparagine synthetase levels may be a consequence of a direct role of tRNAAsn in the regulation of the in vivo expression of the asparagine synthetase structural gene."}
{"id": "PMID:18736", "title": "Isolation of a chloroplast N,N'-dicyclohexylcarbodiimide-binding proteolipid, active in proton translocation.", "content": "The N,N'-dicyclohexylcarbodiimide-binding proteolipid from lettuce chloroplast membranes has been purified by a novel, rapid technique involving I-butanol extraction and ether precipitation. Reconstitution of this proteolipid into liposomes composed of chloroplast lipids and subsequent incorporation of bacteriorhodopsin resulted in the formation of liposomes exhibiting a light-dependent accumulation of protons. This accumulation was significantly enhanced upon addition of N,N'-dicyclohexylcarbodiimide at concentrations similar to those that inhibit chloroplast adenosinetriphosphatase activity. Radioactively labeled N,N'-dicyclohexylcarbodiimide was found to be incorporated essentially into the proteolipid of the reconstituted liposomes. These results suggest that the functional unit responsible for proton channeling in the chloroplast membrane has been isolated and reconstituted in the native state.", "contents": "Isolation of a chloroplast N,N'-dicyclohexylcarbodiimide-binding proteolipid, active in proton translocation. The N,N'-dicyclohexylcarbodiimide-binding proteolipid from lettuce chloroplast membranes has been purified by a novel, rapid technique involving I-butanol extraction and ether precipitation. Reconstitution of this proteolipid into liposomes composed of chloroplast lipids and subsequent incorporation of bacteriorhodopsin resulted in the formation of liposomes exhibiting a light-dependent accumulation of protons. This accumulation was significantly enhanced upon addition of N,N'-dicyclohexylcarbodiimide at concentrations similar to those that inhibit chloroplast adenosinetriphosphatase activity. Radioactively labeled N,N'-dicyclohexylcarbodiimide was found to be incorporated essentially into the proteolipid of the reconstituted liposomes. These results suggest that the functional unit responsible for proton channeling in the chloroplast membrane has been isolated and reconstituted in the native state."}
{"id": "PMID:18744", "title": "Lack of effect of chronically administered thyrotropin-releasing hormone (TRH) on regional rat brain tyrosine hydroxylase activity.", "content": "Chronic treatment of adult male rats with TRH (1 or 10 mg/kg IP) for 5 or 9 days failed to alter the activity of tyrosine hydroxylase (TH), the enzyme regulating the rate-limiting step in catecholamine biosynthesis. In contrast, as previously described, chronic reserpine administration (0.5 mg/kg IP: 9 days) resulted in a significant rise in TH activity in midbrain, hypothalamus, pons-medulla and forebrain. These results suggest that the enhanced brain norepinephrine turnover reported to occur after treatment with TRH is not due to synthesis of new TH enzyme protein.", "contents": "Lack of effect of chronically administered thyrotropin-releasing hormone (TRH) on regional rat brain tyrosine hydroxylase activity. Chronic treatment of adult male rats with TRH (1 or 10 mg/kg IP) for 5 or 9 days failed to alter the activity of tyrosine hydroxylase (TH), the enzyme regulating the rate-limiting step in catecholamine biosynthesis. In contrast, as previously described, chronic reserpine administration (0.5 mg/kg IP: 9 days) resulted in a significant rise in TH activity in midbrain, hypothalamus, pons-medulla and forebrain. These results suggest that the enhanced brain norepinephrine turnover reported to occur after treatment with TRH is not due to synthesis of new TH enzyme protein."}
{"id": "PMID:18746", "title": "Phosphohistone and glycogen synthase D phosphatase activities in a liver glycogen pellet preparation.", "content": "A liver glycogen pellet preparation previously found to contain synthase D phosphatase activity was shown to contain also phosphohistone phosphatase activity. Pellet phosphohistone phosphatase and synthase D phosphatase competed for the same substrates and appeared to be the same enzyme. ATP, a potent inhibitor, and G-6-P, a potent activator of the synthase phosphatase reaction, had little effect on the phosphohistone phosphatase reaction. These observations suggest that the ATP and G-6-P effects are relatively specific and are probably caused by binding to the synthase D substrate. The observed effects of NaCl and KCl were more complex. They stimulated phosphohistone phosphatase activity but strikingly inhibited synthase phosphatase activity. Sodium fluoride inhibited both reactions.", "contents": "Phosphohistone and glycogen synthase D phosphatase activities in a liver glycogen pellet preparation. A liver glycogen pellet preparation previously found to contain synthase D phosphatase activity was shown to contain also phosphohistone phosphatase activity. Pellet phosphohistone phosphatase and synthase D phosphatase competed for the same substrates and appeared to be the same enzyme. ATP, a potent inhibitor, and G-6-P, a potent activator of the synthase phosphatase reaction, had little effect on the phosphohistone phosphatase reaction. These observations suggest that the ATP and G-6-P effects are relatively specific and are probably caused by binding to the synthase D substrate. The observed effects of NaCl and KCl were more complex. They stimulated phosphohistone phosphatase activity but strikingly inhibited synthase phosphatase activity. Sodium fluoride inhibited both reactions."}
{"id": "PMID:18750", "title": "Antagonism of the analeptic activity of thyrotropin-releasing hormone (TRH) by agents which enhance GABA transmission.", "content": "Administration of 10 mg/kg TRH to mice was found to reduce the sleep and hypothermia induced by 4.7 g/kg ethanol. However, TRH did not reduce the sleep of mice that were given gamma-hydroxybutyric acid (GHBA), baclophen, or aminooxyacetic acid (AOAA) in combination with 3 g/kg/ ethanol. TRH also failed to reverse the hypothermia induced by the combination of ethanol and baclophen or GHBA, and the characteristic neurological effects of TRH e.g. tremor, increased muscle tone, and increased respiratory rate were reduced. In addition, TRH-induced locomotor stimulation was prevented by pretreatment with small doses of the GABA-ergic agents, and while 30 mg/kg TRH reduced the hypothermia produced by large doses of the GABA-ergic drugs, it did not antagonize the locomotor retardation produced by baclophen or GHBA. A hypothesis that the analeptic effects of TRH may be medicated via an inhibition of GABA systems is discussed.", "contents": "Antagonism of the analeptic activity of thyrotropin-releasing hormone (TRH) by agents which enhance GABA transmission. Administration of 10 mg/kg TRH to mice was found to reduce the sleep and hypothermia induced by 4.7 g/kg ethanol. However, TRH did not reduce the sleep of mice that were given gamma-hydroxybutyric acid (GHBA), baclophen, or aminooxyacetic acid (AOAA) in combination with 3 g/kg/ ethanol. TRH also failed to reverse the hypothermia induced by the combination of ethanol and baclophen or GHBA, and the characteristic neurological effects of TRH e.g. tremor, increased muscle tone, and increased respiratory rate were reduced. In addition, TRH-induced locomotor stimulation was prevented by pretreatment with small doses of the GABA-ergic agents, and while 30 mg/kg TRH reduced the hypothermia produced by large doses of the GABA-ergic drugs, it did not antagonize the locomotor retardation produced by baclophen or GHBA. A hypothesis that the analeptic effects of TRH may be medicated via an inhibition of GABA systems is discussed."}
{"id": "PMID:18751", "title": "Benzodiazepines and discrimination behaviour: dissociation of response and sensory factors.", "content": "Ten London pigeons were trained on a schedule which allowed concurrent measurement of motor and exteroceptive sensory changes. The task involved a conditional colour discrimination contingent upon the completion of a fixed interval schedule of responding. As a preliminary pharmacological study the effects of the benzodiazepines, chlordiazepoxide and flurazepam were investigated. Both drugs enhanced perseverative responding (after completion of the FI), and to a variable degree responding during the FI, although there was no evidence for an increase in responding during the inter-trial-intervals. On the other hand, no marked changes in discrimination performance were observed. It is concluded that the most significant effects of these benzodiazepines are on motor mechanisms.", "contents": "Benzodiazepines and discrimination behaviour: dissociation of response and sensory factors. Ten London pigeons were trained on a schedule which allowed concurrent measurement of motor and exteroceptive sensory changes. The task involved a conditional colour discrimination contingent upon the completion of a fixed interval schedule of responding. As a preliminary pharmacological study the effects of the benzodiazepines, chlordiazepoxide and flurazepam were investigated. Both drugs enhanced perseverative responding (after completion of the FI), and to a variable degree responding during the FI, although there was no evidence for an increase in responding during the inter-trial-intervals. On the other hand, no marked changes in discrimination performance were observed. It is concluded that the most significant effects of these benzodiazepines are on motor mechanisms."}
{"id": "PMID:18752", "title": "Effect of apomorphine on the antinociceptive activity of morphine.", "content": "Apomorphine pretreatment potentiated the analgesic effect of morphine in a dose-dependent manner both in rats and in mice measured by five different tests (writhing, hot plate, inflamed foot, tail-pinch and tail-flick procedures). Furthermore, apomorphine augmented the antinociceptive activity of morphine in tolerant animals as well. In morphine dependent mice the nalorphine precipitated jumping--a withdrawal symptom--was found inhibited by apomorphine treatment. The results are discussed in the light of the numerous but contradictory data available in the literature.", "contents": "Effect of apomorphine on the antinociceptive activity of morphine. Apomorphine pretreatment potentiated the analgesic effect of morphine in a dose-dependent manner both in rats and in mice measured by five different tests (writhing, hot plate, inflamed foot, tail-pinch and tail-flick procedures). Furthermore, apomorphine augmented the antinociceptive activity of morphine in tolerant animals as well. In morphine dependent mice the nalorphine precipitated jumping--a withdrawal symptom--was found inhibited by apomorphine treatment. The results are discussed in the light of the numerous but contradictory data available in the literature."}
{"id": "PMID:18766", "title": "Assay and characterization of serum-stimulated lipolytic activity in homogenates of human adipose tissue.", "content": "An assay of lipolytic activity in human adipose tissue is described, in which native homogenates of the adipose tissue yield the enzyme, as well as the triglyceride substrate, and the emulsifying phospholipids. The lipolytic activity in the presence of serum is characterized mainly as lipoprotein lipase activity by a pH-optimum of 8.0, by the fact that serum is necessary for full activity, and that it is inhibited by 1 M NaCl and by protamine. At serum concentrations of higher than 50% a marked inhibition of the lipolysis is observed. Noradrenaline, insulin, and heparin have no effect on the serum-stimulated lipolytic activity.", "contents": "Assay and characterization of serum-stimulated lipolytic activity in homogenates of human adipose tissue. An assay of lipolytic activity in human adipose tissue is described, in which native homogenates of the adipose tissue yield the enzyme, as well as the triglyceride substrate, and the emulsifying phospholipids. The lipolytic activity in the presence of serum is characterized mainly as lipoprotein lipase activity by a pH-optimum of 8.0, by the fact that serum is necessary for full activity, and that it is inhibited by 1 M NaCl and by protamine. At serum concentrations of higher than 50% a marked inhibition of the lipolysis is observed. Noradrenaline, insulin, and heparin have no effect on the serum-stimulated lipolytic activity."}
{"id": "PMID:18767", "title": "Oxygen affinity of duck blood determined by in vivo and in vitro technique.", "content": "Half saturation partial pressure of O2,P50, was determined in domestic Muscovy ducks (Cairina moschata) both by in vivo and in vitro techniques. For in vivo determination, blood samples were drawn from the anesthetized, artificially ventilated animals and analyzed both for O2 content, Co2, and O2 partial pressure, Po2. O2 capacity was detemined in arterial samples during hyperoxic ventilation (arterial Po2 about 180 torr). P50 was calculated from measurements in venous blood samples (O2 saturation near 50%). For in vitro determinations, Co2 was measured in blood samples equilibrated with Po2 close to P50. No significant difference was found between P50 values determined by both techniques. At 41 C and pH 7.50, P50 averaged 41.7 torr when analyzed by in vivo technique and 41.4 torr when determined in vitro. The variability between animals was less than 1 torr (SD) and could be explained by the experimental error. The partially discordant literature data on P50 of duck blood are reviewed and critically discussed.", "contents": "Oxygen affinity of duck blood determined by in vivo and in vitro technique. Half saturation partial pressure of O2,P50, was determined in domestic Muscovy ducks (Cairina moschata) both by in vivo and in vitro techniques. For in vivo determination, blood samples were drawn from the anesthetized, artificially ventilated animals and analyzed both for O2 content, Co2, and O2 partial pressure, Po2. O2 capacity was detemined in arterial samples during hyperoxic ventilation (arterial Po2 about 180 torr). P50 was calculated from measurements in venous blood samples (O2 saturation near 50%). For in vitro determinations, Co2 was measured in blood samples equilibrated with Po2 close to P50. No significant difference was found between P50 values determined by both techniques. At 41 C and pH 7.50, P50 averaged 41.7 torr when analyzed by in vivo technique and 41.4 torr when determined in vitro. The variability between animals was less than 1 torr (SD) and could be explained by the experimental error. The partially discordant literature data on P50 of duck blood are reviewed and critically discussed."}
{"id": "PMID:18787", "title": "Inhibition of secretin release and pancreatic bicarbonate secretion by somatostatin infusion in man.", "content": "Five healthy students were investigated on two different days with or without a constant infusion of somatostatin (500 microgram/h) into an arm vein a fluoroscopically placed Lagerl\u00f6f tube was used for the collection of gastric and duodenal juice. After 30-min basal period, 40 ml 100 mmol/l HCl was infused into the midpart of the duodenum over 5 min through a thin catheter attached to the tube. Plasma immunoreactive secretin was measured by radioimmunoassay employing 125I-labelled synthetic secretin, antibody against synthetic secretin, and standards prepared from pure natural porcine secretin. Secretin levels without somatostatin infusion were 4.6+/-0.7 pmol/l (mean+/-S.E.M.) basally and rose to a peak of 21.8+/-6.2 pmol/l after duodenal acidification (p less than 0.05) and with somatostatin infusion were 4.4+/-0.4 pmol/l basally and rose to a peak of 6.7+/-1.7 pmol/l (n.s.) after duodenal acidification. Pancreatic bicarbonate output increased from 8.0+/-2.5 mumol/min (mean+/-S.E.M.) to 283+/-44 mumol/min without somatostatin infusion (p less than 0.05) and from 6.7+/-2.1 mumol/min to 70+/-13 mumol/min somatostatin (p less than 0.05). This study shows that somatostatin (500 microgram/h can inhibit the release of secretin and the pancreatic bicarbonate secretion after duodenal acidification in man.", "contents": "Inhibition of secretin release and pancreatic bicarbonate secretion by somatostatin infusion in man. Five healthy students were investigated on two different days with or without a constant infusion of somatostatin (500 microgram/h) into an arm vein a fluoroscopically placed Lagerl\u00f6f tube was used for the collection of gastric and duodenal juice. After 30-min basal period, 40 ml 100 mmol/l HCl was infused into the midpart of the duodenum over 5 min through a thin catheter attached to the tube. Plasma immunoreactive secretin was measured by radioimmunoassay employing 125I-labelled synthetic secretin, antibody against synthetic secretin, and standards prepared from pure natural porcine secretin. Secretin levels without somatostatin infusion were 4.6+/-0.7 pmol/l (mean+/-S.E.M.) basally and rose to a peak of 21.8+/-6.2 pmol/l after duodenal acidification (p less than 0.05) and with somatostatin infusion were 4.4+/-0.4 pmol/l basally and rose to a peak of 6.7+/-1.7 pmol/l (n.s.) after duodenal acidification. Pancreatic bicarbonate output increased from 8.0+/-2.5 mumol/min (mean+/-S.E.M.) to 283+/-44 mumol/min without somatostatin infusion (p less than 0.05) and from 6.7+/-2.1 mumol/min to 70+/-13 mumol/min somatostatin (p less than 0.05). This study shows that somatostatin (500 microgram/h can inhibit the release of secretin and the pancreatic bicarbonate secretion after duodenal acidification in man."}
{"id": "PMID:18788", "title": "Gastro-oesophageal sphincter pressure, motility and acid clearing. A study of hiatus hernia patients and normal subjects and of the effect of a modified belsey MK IV repair on the results of the manometric and acid-clearing tests.", "content": "Basal gastro-oesophageal sphincter pressure was recorded in 68 patients with symptomatic, radiologically verified sliding hiatus hernia, and in 37 healthy subjects. The diameter of the probe was 2.5 mm, and the flow rate 0.5 ml/min. Mean sphincter pressure was lower in patients (6 mm Hg) than in normal subjects (15 mm Hg). In 32 per cent of the patients sphincter pressure was within normal range (8-24 mm Hg), whereas in 68 per cent it was lower than in the normal subjects. There seemed to be no relationship between sphincter pressure and severity of symptoms. Oesophageal acid clearing was investigated in 57 of the patients and in 26 of the normal subjects. Normal subjects clear the bolus of acid in an average of 10 swallows (range 4-16). In patients the incidence of prolonged clearing was greater, but the acid-clearing ability did not seem to be related to the degree of severity of the symptoms. A manometric study was made of 45 patients and an acid-clearing study made of 40 patients, before and 3 months after a modified Belsey MK IV repair for hiatal hernia. Mean postoperative sphincter pressure was higher (10 mm Hg) than the preoperative mean (6 mm Hg), but was still lower than the normal mean. Significant changes in acid-clearing ability could not be demonstrated. The results are inconclusive with regard to the importance of oesophageal motility disturbances for the symptomatology and acid-clearing ability. Thirty-seven out of 45 patients became free of symptoms, and the rest - except 1 (relapse of hernia) - improved.", "contents": "Gastro-oesophageal sphincter pressure, motility and acid clearing. A study of hiatus hernia patients and normal subjects and of the effect of a modified belsey MK IV repair on the results of the manometric and acid-clearing tests. Basal gastro-oesophageal sphincter pressure was recorded in 68 patients with symptomatic, radiologically verified sliding hiatus hernia, and in 37 healthy subjects. The diameter of the probe was 2.5 mm, and the flow rate 0.5 ml/min. Mean sphincter pressure was lower in patients (6 mm Hg) than in normal subjects (15 mm Hg). In 32 per cent of the patients sphincter pressure was within normal range (8-24 mm Hg), whereas in 68 per cent it was lower than in the normal subjects. There seemed to be no relationship between sphincter pressure and severity of symptoms. Oesophageal acid clearing was investigated in 57 of the patients and in 26 of the normal subjects. Normal subjects clear the bolus of acid in an average of 10 swallows (range 4-16). In patients the incidence of prolonged clearing was greater, but the acid-clearing ability did not seem to be related to the degree of severity of the symptoms. A manometric study was made of 45 patients and an acid-clearing study made of 40 patients, before and 3 months after a modified Belsey MK IV repair for hiatal hernia. Mean postoperative sphincter pressure was higher (10 mm Hg) than the preoperative mean (6 mm Hg), but was still lower than the normal mean. Significant changes in acid-clearing ability could not be demonstrated. The results are inconclusive with regard to the importance of oesophageal motility disturbances for the symptomatology and acid-clearing ability. Thirty-seven out of 45 patients became free of symptoms, and the rest - except 1 (relapse of hernia) - improved."}
{"id": "PMID:18789", "title": "Enzymatic Determination of bile acids. the NADP-specific 7alpha-hydroxysteroid dehydrogenase from P. testosteroni (ATCC 11996).", "content": "By use of the specific substrates, 7alpha-hydroxy-5beta-cholanic acid and 3alpha, 7alpha, 12alpha-trihydroxy-3,12-diacetyl-5beta-cholanic acid methyl ester, crude extracts of P. testosteroni grown on a steroid-containing medium have been shown to exhibit 7alpha-hydroxysteroid: NADP-oxidoreductase activity. The enzyme is highly specific for NADP. Both free and conjugated 7alpha-hydroxy bile acids can act as substrates, but those of low polarity (few hydroxyl groups) seem to be preferred, judging from initial reaction velocity studies. Optimal conditions appears to be at pH 8.5-9.5 and at 25 degress C. Free SH-groups are essential for maximum catalytic activity, since the enzyme is inhibited by SH-reacting substances such as p-chloromercuribenzoate and monoiodoacetic acid. Also the ketone-trapping agents hydrazine hydrate and semicarbazide act as inhibitors. Upon dilution, the storage stability is severely reduced, but this effect may be counteracted by the addition of glycerol at concentration of 20% or more. By gel filtration experiments on Sephadex G-100, the molecular weight was estimated to about 80,000.", "contents": "Enzymatic Determination of bile acids. the NADP-specific 7alpha-hydroxysteroid dehydrogenase from P. testosteroni (ATCC 11996). By use of the specific substrates, 7alpha-hydroxy-5beta-cholanic acid and 3alpha, 7alpha, 12alpha-trihydroxy-3,12-diacetyl-5beta-cholanic acid methyl ester, crude extracts of P. testosteroni grown on a steroid-containing medium have been shown to exhibit 7alpha-hydroxysteroid: NADP-oxidoreductase activity. The enzyme is highly specific for NADP. Both free and conjugated 7alpha-hydroxy bile acids can act as substrates, but those of low polarity (few hydroxyl groups) seem to be preferred, judging from initial reaction velocity studies. Optimal conditions appears to be at pH 8.5-9.5 and at 25 degress C. Free SH-groups are essential for maximum catalytic activity, since the enzyme is inhibited by SH-reacting substances such as p-chloromercuribenzoate and monoiodoacetic acid. Also the ketone-trapping agents hydrazine hydrate and semicarbazide act as inhibitors. Upon dilution, the storage stability is severely reduced, but this effect may be counteracted by the addition of glycerol at concentration of 20% or more. By gel filtration experiments on Sephadex G-100, the molecular weight was estimated to about 80,000."}
{"id": "PMID:18790", "title": "Quantitative determination of serum bile acids using a 7alpha-hydroxysteroid dehydrogenase.", "content": "A crude 7alpha-hydroxysteroid dehydrogenase isolate from P. testosteroni requires NADP specifically and provides a simple and specific means for the determination of 7alpha-hydroxy bile acids and their conjugates. A specific and reliable enzymatic-fluorimetric method for the quantitative measurement of the primary bile acids in serum is described. Overall recovery from normal and jaundiced serum averaged 85%. The mean concentration of serum 7alpha-hydroxy bile acids in fasting, healthy subjects was 2.5 mumoles/1 (S.D. 1.45 AND RANGE 1.2-6.3), averaging 73% (S.D. 11.5) of the total, measured as the 3alpha-hydroxy bile acid concentration. In parenchymatous liver disease and cholestatic hepatobiliary disorders, the proportion of 7alpha-hydroxy bile acids was significantly increased, mean 92.5% (S.D. 6.6)(p less than 0.001).", "contents": "Quantitative determination of serum bile acids using a 7alpha-hydroxysteroid dehydrogenase. A crude 7alpha-hydroxysteroid dehydrogenase isolate from P. testosteroni requires NADP specifically and provides a simple and specific means for the determination of 7alpha-hydroxy bile acids and their conjugates. A specific and reliable enzymatic-fluorimetric method for the quantitative measurement of the primary bile acids in serum is described. Overall recovery from normal and jaundiced serum averaged 85%. The mean concentration of serum 7alpha-hydroxy bile acids in fasting, healthy subjects was 2.5 mumoles/1 (S.D. 1.45 AND RANGE 1.2-6.3), averaging 73% (S.D. 11.5) of the total, measured as the 3alpha-hydroxy bile acid concentration. In parenchymatous liver disease and cholestatic hepatobiliary disorders, the proportion of 7alpha-hydroxy bile acids was significantly increased, mean 92.5% (S.D. 6.6)(p less than 0.001)."}
{"id": "PMID:18791", "title": "Effect of cimetidine on pentagastrin-stimulated gastric secretion in healthy man.", "content": "Two series of experiments were carried out in three healthy volunteers. In one series increasing doses of cimetidine were tested on a constant background stimulation with 0.15 microgram-kg-1h-1 of pentagastrin. In the other series of experiments increasing doses of pentagastrin were given either alone or in combination with a fixed dose of cimetidine (1.2 mg-kg-1h-1). Pentagastrin and cimetidine were given as continuous intravenous infusions, the various doses tested on separate days. The inhibition of acid output in response to pentagastrin stimulation increased almost linearly with the log dose of cimetidine. Fifty per cent inhibition of the response to 0.15 microgram-kg-1h-1 of pentagastrin was achieved by about 0.6 mg-kg-1h-1 of cimetidine. 2.4 mg-kg-1h-1 of cimetidine gave on average 90% inhibition. The inhibition caused by cimetidine decreased to a minimum of 57% and could not be overcome by increasing the doses of pentagastrin. The results suggest a mixture of competitive and noncompetitive interaction. The effect of cimetidine on pepsin secretion was less regular. Generally, pepsin output was less inhibited than acid output.", "contents": "Effect of cimetidine on pentagastrin-stimulated gastric secretion in healthy man. Two series of experiments were carried out in three healthy volunteers. In one series increasing doses of cimetidine were tested on a constant background stimulation with 0.15 microgram-kg-1h-1 of pentagastrin. In the other series of experiments increasing doses of pentagastrin were given either alone or in combination with a fixed dose of cimetidine (1.2 mg-kg-1h-1). Pentagastrin and cimetidine were given as continuous intravenous infusions, the various doses tested on separate days. The inhibition of acid output in response to pentagastrin stimulation increased almost linearly with the log dose of cimetidine. Fifty per cent inhibition of the response to 0.15 microgram-kg-1h-1 of pentagastrin was achieved by about 0.6 mg-kg-1h-1 of cimetidine. 2.4 mg-kg-1h-1 of cimetidine gave on average 90% inhibition. The inhibition caused by cimetidine decreased to a minimum of 57% and could not be overcome by increasing the doses of pentagastrin. The results suggest a mixture of competitive and noncompetitive interaction. The effect of cimetidine on pepsin secretion was less regular. Generally, pepsin output was less inhibited than acid output."}
{"id": "PMID:18792", "title": "Microcalorimetric studies of human platelet metabolism at rest. Influence of pH, temperature, cell concentration, preparation methods and storage.", "content": "Heat production in human platelets has been measured under different conditions of pH, temp., cell concentration, preparation and storage time. The heat effect was found to increase linearly in the pH range 7.00-7.95, by 20% per pH unit. The temp. coefficient for the heat effect was determined to be Q10 = 2.0 for the temp. interval 32-42 degrees C. Heat production per cell was not significantly affected by variations in cell concentration, or by storage for several hours at room temp. When citrate replaced heparin as anticoagulant significantly higher heat effect values were found.", "contents": "Microcalorimetric studies of human platelet metabolism at rest. Influence of pH, temperature, cell concentration, preparation methods and storage. Heat production in human platelets has been measured under different conditions of pH, temp., cell concentration, preparation and storage time. The heat effect was found to increase linearly in the pH range 7.00-7.95, by 20% per pH unit. The temp. coefficient for the heat effect was determined to be Q10 = 2.0 for the temp. interval 32-42 degrees C. Heat production per cell was not significantly affected by variations in cell concentration, or by storage for several hours at room temp. When citrate replaced heparin as anticoagulant significantly higher heat effect values were found."}
{"id": "PMID:18793", "title": "A deficient pyruvate kinase with an electrophoretically slow-moving component.", "content": "A deficient erythrocyte pyruvate kinase observed in a patient with congenital non-spherocytic anaemia was characterized by the following properties: very low activity in haemolysates, decreased thermal stability, slightly increased urea denaturation, high affinity for PEP, poor FDP activation, normal ATP inhibition, decreased affinity for ADP, normal pH of optimal activity, and presence of an abnormal slow-moving component in this layer polyacrylamide gel electrophoresis. The patient was probably double heterozygous for two different deficient mutants of erythrocyte pyruvate kinase.", "contents": "A deficient pyruvate kinase with an electrophoretically slow-moving component. A deficient erythrocyte pyruvate kinase observed in a patient with congenital non-spherocytic anaemia was characterized by the following properties: very low activity in haemolysates, decreased thermal stability, slightly increased urea denaturation, high affinity for PEP, poor FDP activation, normal ATP inhibition, decreased affinity for ADP, normal pH of optimal activity, and presence of an abnormal slow-moving component in this layer polyacrylamide gel electrophoresis. The patient was probably double heterozygous for two different deficient mutants of erythrocyte pyruvate kinase."}
{"id": "PMID:18795", "title": "Asthma and urticaria during disodium cromoglycate treatment. A case report.", "content": "A 10-year-old asthmatic boy began to suffer from urticarial rash and moderately severe bronchospasm after 8 weeks' treatment with disodium cromoglycate. Initially, DSCG had helped to control his asthmatic attacks, and steroid therapy could be discontinued. Inhalation provocation test with DSCG aerosol, 4 months after stopping DSCG treatment, showed an immediate-type 1 response and urticaria. A repeat provocation test, under antihistaminic cover , failed to produce similar response. When DSCG was withdrawn, urticaria vanished and the child remained symptom-free. Disodium cromoglycate is regarded as the possible aetiological agent.", "contents": "Asthma and urticaria during disodium cromoglycate treatment. A case report. A 10-year-old asthmatic boy began to suffer from urticarial rash and moderately severe bronchospasm after 8 weeks' treatment with disodium cromoglycate. Initially, DSCG had helped to control his asthmatic attacks, and steroid therapy could be discontinued. Inhalation provocation test with DSCG aerosol, 4 months after stopping DSCG treatment, showed an immediate-type 1 response and urticaria. A repeat provocation test, under antihistaminic cover , failed to produce similar response. When DSCG was withdrawn, urticaria vanished and the child remained symptom-free. Disodium cromoglycate is regarded as the possible aetiological agent."}
{"id": "PMID:18796", "title": "[Effect of alclofenac on the prothrombin level in patients under treatment with anticoagulants].", "content": "Simultaneous administration of the anticoagulants acenocoumarol, phenprocoumon or chlorindion and the antirheumatic substance alclofenac in long term trials has no observable influence on the prothrombin time of stabilized patients. When the anticoagulant (acenocoumarol or phenprocoumon) and the alclofenac therapy are begun simultaneously, a variation of the dose is necessary. Either a one-third lower initial dosage can be given, or, after attaining the maximal anticoagulation effect on the prothrombin time (48 h after beginning acenocoumarol therapy, 72 h with phenprocoumarol), a lower daily dosage must be administered once, in comparison to the other group without alclofenac therapy. The maintenace dosage is not influenced by alclofenac.", "contents": "[Effect of alclofenac on the prothrombin level in patients under treatment with anticoagulants]. Simultaneous administration of the anticoagulants acenocoumarol, phenprocoumon or chlorindion and the antirheumatic substance alclofenac in long term trials has no observable influence on the prothrombin time of stabilized patients. When the anticoagulant (acenocoumarol or phenprocoumon) and the alclofenac therapy are begun simultaneously, a variation of the dose is necessary. Either a one-third lower initial dosage can be given, or, after attaining the maximal anticoagulation effect on the prothrombin time (48 h after beginning acenocoumarol therapy, 72 h with phenprocoumarol), a lower daily dosage must be administered once, in comparison to the other group without alclofenac therapy. The maintenace dosage is not influenced by alclofenac."}
{"id": "PMID:18800", "title": "An entomological survey on the mosquitoes of Wuvulu Island, Papua-New Guinea.", "content": "An entomological survey in Wuvulu Island, Papua New Guinea, in August 1975 and 1976 shows the presence of six mosquito species: Aedes (S.) hebrideus, AE. (F.) notoscriptus, AE. (V.) lineatus, ? Ae. (L.) dasyorrhus, Culex pipiens fatigans and Armigeres breinli. The medical significance of these mosquitoes is discussed, with special reference to the problem of dengue virus transmission.", "contents": "An entomological survey on the mosquitoes of Wuvulu Island, Papua-New Guinea. An entomological survey in Wuvulu Island, Papua New Guinea, in August 1975 and 1976 shows the presence of six mosquito species: Aedes (S.) hebrideus, AE. (F.) notoscriptus, AE. (V.) lineatus, ? Ae. (L.) dasyorrhus, Culex pipiens fatigans and Armigeres breinli. The medical significance of these mosquitoes is discussed, with special reference to the problem of dengue virus transmission."}
{"id": "PMID:18801", "title": "The effect of acid-stimulating and inhibiting drugs on the ultrastructure of gastric parietal cells in man.", "content": "The ultrastructure of the human parietal cell at rest, after stimulation of gastric acid secretion by pentagastrin and after inhibition with propantheline or cimetidine, an H2-receptor antagonist, was studied. On stimulation there was an increase in the total secretory surface area of the gastric gland and canaliculus, with a concomitant decrease in the tubulovesicular system. On inhibition there was a decrease in the secretory surface area and a corresponding increase in the tubulovesicular system. These results are in agreement with other reports and support the hypothesis that during secretion of acid the tubulovesicular system increases the secretory surface by eversion or fusion of the vesicles and tubules with the plasmalemma. On inhibition there is thought to be reformation of the tubulovesicular system by pinocytosis. There is also ultrastructural evidence for the theory of membrane flow between the tubulovesicular system and the microvilli of the canaliculus and gastric lumen. Furthermore, there was an increase in lysosomal activity after the administration of the inhibiting drugs. It is suggested that the increased lysosomal activity could be involved in reducing the quantity of membrane after the membrane flow which occurs on gastric acid inhibition.", "contents": "The effect of acid-stimulating and inhibiting drugs on the ultrastructure of gastric parietal cells in man. The ultrastructure of the human parietal cell at rest, after stimulation of gastric acid secretion by pentagastrin and after inhibition with propantheline or cimetidine, an H2-receptor antagonist, was studied. On stimulation there was an increase in the total secretory surface area of the gastric gland and canaliculus, with a concomitant decrease in the tubulovesicular system. On inhibition there was a decrease in the secretory surface area and a corresponding increase in the tubulovesicular system. These results are in agreement with other reports and support the hypothesis that during secretion of acid the tubulovesicular system increases the secretory surface by eversion or fusion of the vesicles and tubules with the plasmalemma. On inhibition there is thought to be reformation of the tubulovesicular system by pinocytosis. There is also ultrastructural evidence for the theory of membrane flow between the tubulovesicular system and the microvilli of the canaliculus and gastric lumen. Furthermore, there was an increase in lysosomal activity after the administration of the inhibiting drugs. It is suggested that the increased lysosomal activity could be involved in reducing the quantity of membrane after the membrane flow which occurs on gastric acid inhibition."}
{"id": "PMID:18802", "title": "The effect of cyclizine hydrochloride on lower oesophageal sphincter pressure in man.", "content": "Gastro-oesophageal reflux and pulmonary aspiration of acid gastric content remain significant causes of morbidity and mortality. A drug which increases lower oesophageal sphincter (LOS) tone would reduce this hazard. The effect of LOS function of intravenous cyclizine (25 mg), in half the recommended adult dose, was investigated in 8 volunteers. Cyclizine increased the LOS pressure by an average of 14,4 cm H2O (P less than 0,005). Cyclizine, like metoclopramide, has a desirable functional effect on the LOS. Both drugs are, in addition, potent anti-emetics. On the grounds of these pharmacological properties they are recommended in the preparation of patients for emergency surgery.", "contents": "The effect of cyclizine hydrochloride on lower oesophageal sphincter pressure in man. Gastro-oesophageal reflux and pulmonary aspiration of acid gastric content remain significant causes of morbidity and mortality. A drug which increases lower oesophageal sphincter (LOS) tone would reduce this hazard. The effect of LOS function of intravenous cyclizine (25 mg), in half the recommended adult dose, was investigated in 8 volunteers. Cyclizine increased the LOS pressure by an average of 14,4 cm H2O (P less than 0,005). Cyclizine, like metoclopramide, has a desirable functional effect on the LOS. Both drugs are, in addition, potent anti-emetics. On the grounds of these pharmacological properties they are recommended in the preparation of patients for emergency surgery."}
{"id": "PMID:18806", "title": "The role of adrenergic stimulation in the pathogenesis of pulmonary insufficiency.", "content": "Recent studies have shown that epinephrine (E), norepinephrine (NE), and isoproterenol (I) caus'e substantial pulmonary shunting. This study was undertaken to determine the role of alpha (pulmonary vasconconstriction) and beta (pulmonary vasodilatation) adrenergic stimulation in the pathogenesis of pulmonary insufficiency. Forty-three mechanically ventilated, anesthetized dogs received infusions of E, alpha and beta stimulant; NE, a relatively pure alpha stimulant; I, a relatively pure beta stimulant; and dextran (D), a drug with no known adrenergic activity. The cardiac output and shunt measurements were determined simultaneously in the control period and four times during a 1 hour infusion. The quadratic equation of best fit was determined for each group for the relationship between the cardiac output and the shunt over a wide range of cardiac outputs, and statistical comparisons were made between all groups of the shunt at the same cardiac output. In all groups an increase in cardiac output was associated with an increase in the shunt, but the magnitude of the increase in the shunt differed significantly with each drug over the entire range, being smallest with D and becoming progressively larger with I, E, and NE, respectively. It is concluded that an increase in the pulmonary blood flow causes an increase in the pulmonary shunt, but that the magnitude of the increase is dependent on the specific pulmonary microcirculatory effects of each drug.", "contents": "The role of adrenergic stimulation in the pathogenesis of pulmonary insufficiency. Recent studies have shown that epinephrine (E), norepinephrine (NE), and isoproterenol (I) caus'e substantial pulmonary shunting. This study was undertaken to determine the role of alpha (pulmonary vasconconstriction) and beta (pulmonary vasodilatation) adrenergic stimulation in the pathogenesis of pulmonary insufficiency. Forty-three mechanically ventilated, anesthetized dogs received infusions of E, alpha and beta stimulant; NE, a relatively pure alpha stimulant; I, a relatively pure beta stimulant; and dextran (D), a drug with no known adrenergic activity. The cardiac output and shunt measurements were determined simultaneously in the control period and four times during a 1 hour infusion. The quadratic equation of best fit was determined for each group for the relationship between the cardiac output and the shunt over a wide range of cardiac outputs, and statistical comparisons were made between all groups of the shunt at the same cardiac output. In all groups an increase in cardiac output was associated with an increase in the shunt, but the magnitude of the increase in the shunt differed significantly with each drug over the entire range, being smallest with D and becoming progressively larger with I, E, and NE, respectively. It is concluded that an increase in the pulmonary blood flow causes an increase in the pulmonary shunt, but that the magnitude of the increase is dependent on the specific pulmonary microcirculatory effects of each drug."}
{"id": "PMID:18807", "title": "Dilemmas in the early diagnosis and treatment of multiple endocrine adenomatosis, type II.", "content": "Fifteen patients with the diagnosis of multiple endocrine adenomatosis, type II, syndrome (MEA II) were reported from a single center to discuss the dilemmas of early detection and treatment of the adrenal medullary, thyroid, and parathyroid gland diseases. Ten patients came from three families. Three of the patients died, none in hypertensive crisis. Bilateral adrenal medullary disease was present in six patients. Five patients with proved pheochromocytoma had hypertension. All had diagnostic urinary catecholamine values. Nine normotensive patients without proved pheochromocytoma but in a high-risk category for adrenal medullary disease, have multiple suspicious urinary cathecholamines suggestive of adrenal medullary hyperplasia. Bilateral adrenalectomy is recommended for proved adrenal medullary disease in the MEA II syndrome. Medullary carcinoma of the thyroid gland was found in 13 patients and is believed to be present in two others. Five of the proved cases were occult, being discovered by elevation of pentagastrin-stimulated serum calcitonin levels, justifying total thyroidectomy. Parathyroid hyperplasia was found in three patients with preoperative hypercalcemia and in four others with preoperative normocalcemia. Conservative treatment of parathyroid gland hyperplasia in the MEA II syndrome is substantiated. Metachronous phenotypic expression of the syndrome components was significant.", "contents": "Dilemmas in the early diagnosis and treatment of multiple endocrine adenomatosis, type II. Fifteen patients with the diagnosis of multiple endocrine adenomatosis, type II, syndrome (MEA II) were reported from a single center to discuss the dilemmas of early detection and treatment of the adrenal medullary, thyroid, and parathyroid gland diseases. Ten patients came from three families. Three of the patients died, none in hypertensive crisis. Bilateral adrenal medullary disease was present in six patients. Five patients with proved pheochromocytoma had hypertension. All had diagnostic urinary catecholamine values. Nine normotensive patients without proved pheochromocytoma but in a high-risk category for adrenal medullary disease, have multiple suspicious urinary cathecholamines suggestive of adrenal medullary hyperplasia. Bilateral adrenalectomy is recommended for proved adrenal medullary disease in the MEA II syndrome. Medullary carcinoma of the thyroid gland was found in 13 patients and is believed to be present in two others. Five of the proved cases were occult, being discovered by elevation of pentagastrin-stimulated serum calcitonin levels, justifying total thyroidectomy. Parathyroid hyperplasia was found in three patients with preoperative hypercalcemia and in four others with preoperative normocalcemia. Conservative treatment of parathyroid gland hyperplasia in the MEA II syndrome is substantiated. Metachronous phenotypic expression of the syndrome components was significant."}
{"id": "PMID:18809", "title": "Potentiation by the injection vehicle of the teratological action of acetazolamide in rats.", "content": "The high alkalinity of the injection vehicle of certain parenteral solutions of acetazolamide produces necrosis of the skin upon sc injection. The possible modification of this effect on the teratogenicity of acetazolamide was examined. Acetazolamide in a vehicle of pH 10.5 produced 36.6% fetal malformations, in a vehicle of pH 8.7, 6.1%, and in neutral suspension, 11.8%. Adrenal medullectomy or phentolamine plus the high pH acetazolamide reduced the frequency to 23.2 and 24.4%, respectively. The teratogenicity of the low pH acetazolamide was increased by epinephrine to 64.2%. The frequency of hemimelia and micromelia, and of bilateral involvement, was greater in litters exposed to the high pH acetazolamide or the epinephrine-acetazolamide combinations, and was reduced by phentolamine or adrenal medullectomy. Neither the high pH vehicle nor epinephrine produced fetal defects in the absence of acetazolamide. The biological disposition of acetazolamide was not altered by any of the treatments. Reduction of uterine blood flow may be responsible for the potentiation of teratogenicity by the high pH vehicle.", "contents": "Potentiation by the injection vehicle of the teratological action of acetazolamide in rats. The high alkalinity of the injection vehicle of certain parenteral solutions of acetazolamide produces necrosis of the skin upon sc injection. The possible modification of this effect on the teratogenicity of acetazolamide was examined. Acetazolamide in a vehicle of pH 10.5 produced 36.6% fetal malformations, in a vehicle of pH 8.7, 6.1%, and in neutral suspension, 11.8%. Adrenal medullectomy or phentolamine plus the high pH acetazolamide reduced the frequency to 23.2 and 24.4%, respectively. The teratogenicity of the low pH acetazolamide was increased by epinephrine to 64.2%. The frequency of hemimelia and micromelia, and of bilateral involvement, was greater in litters exposed to the high pH acetazolamide or the epinephrine-acetazolamide combinations, and was reduced by phentolamine or adrenal medullectomy. Neither the high pH vehicle nor epinephrine produced fetal defects in the absence of acetazolamide. The biological disposition of acetazolamide was not altered by any of the treatments. Reduction of uterine blood flow may be responsible for the potentiation of teratogenicity by the high pH vehicle."}
{"id": "PMID:18811", "title": "Purification and properties of a neutral protease from soil bacterium WM 122.", "content": "An extracellular protease SN 687, secreted by the soil bacterium isolate WM 122, has been purified by means of gel filtration, ammonium sulfate precipitation, DEAE-Sephadex and hydroxylapatite chromatography. Apparent homogeneity was ascertained by polyacrylamide gel electrophoresis. The protease was inactivated by ethylenediamine tetracetic acid (EDTA) but not by diisopropylfluorophosphate (DFP), and it was partially inhibited by serum inhibitors. SN 687 was shown to be of high specific activity against casein and fibrin, but it did not hydrolyze L-lysine-methyl ester dihydrochloride (LME), p-tosyl-L-arginine-methyl ester hydrochloride (TAME) and N-benzoyl-L-tyrosine-ethyl ester hydrochloride (BTEE) synthetic substrates. The optimum pH for hydrolysis of casein was 7.5 and the molecular weight, as determined by gel filtration, was 31,000.", "contents": "Purification and properties of a neutral protease from soil bacterium WM 122. An extracellular protease SN 687, secreted by the soil bacterium isolate WM 122, has been purified by means of gel filtration, ammonium sulfate precipitation, DEAE-Sephadex and hydroxylapatite chromatography. Apparent homogeneity was ascertained by polyacrylamide gel electrophoresis. The protease was inactivated by ethylenediamine tetracetic acid (EDTA) but not by diisopropylfluorophosphate (DFP), and it was partially inhibited by serum inhibitors. SN 687 was shown to be of high specific activity against casein and fibrin, but it did not hydrolyze L-lysine-methyl ester dihydrochloride (LME), p-tosyl-L-arginine-methyl ester hydrochloride (TAME) and N-benzoyl-L-tyrosine-ethyl ester hydrochloride (BTEE) synthetic substrates. The optimum pH for hydrolysis of casein was 7.5 and the molecular weight, as determined by gel filtration, was 31,000."}
{"id": "PMID:18819", "title": "Fetal suppressor cells. Their influence on the cell-mediated immune responses.", "content": "The cell-mediated immune responses are significantly reduced in fetal and newborn mice, furthermore, spleen cells of these animals are able to suppress the immune responses of adult lymphocytes in a variety of situations. Newborn mice sensitized to picryl chloride within 24 hr after birth fail to develop contact sensitivity reaction when tested several weeks later, and fetal mice do not develop graft-versus-host reaction when given injections of parental lymphocytes. Spleen cells of fetal or newborn mice are able to suppress the passive transfer of contact sensitivity and the local graft-versus-host reaction elicited by immunized parental cells in F1 hybrid mice, and reduce significantly the severity of graft-versus-host reaction and mortality rate in cyclophosphamide-treated F1 recipients. In no experiment were thymus cells of either fetal or newborn mice found to be inhibitory. The possible mechanisms of action and biological significance of fetal suppressor cells are discussed.", "contents": "Fetal suppressor cells. Their influence on the cell-mediated immune responses. The cell-mediated immune responses are significantly reduced in fetal and newborn mice, furthermore, spleen cells of these animals are able to suppress the immune responses of adult lymphocytes in a variety of situations. Newborn mice sensitized to picryl chloride within 24 hr after birth fail to develop contact sensitivity reaction when tested several weeks later, and fetal mice do not develop graft-versus-host reaction when given injections of parental lymphocytes. Spleen cells of fetal or newborn mice are able to suppress the passive transfer of contact sensitivity and the local graft-versus-host reaction elicited by immunized parental cells in F1 hybrid mice, and reduce significantly the severity of graft-versus-host reaction and mortality rate in cyclophosphamide-treated F1 recipients. In no experiment were thymus cells of either fetal or newborn mice found to be inhibitory. The possible mechanisms of action and biological significance of fetal suppressor cells are discussed."}
{"id": "PMID:18821", "title": "Graft-versus-host reaction. Influence of genetic background in donor-recipient pairs incompatible for major histocompatibility complex (MHC).", "content": "In two H-2b anti-H-2d but not in H-2b anti-H2k donor-recipient combinations, graft-versus-host reaction (GVHR) mortality was found to vary as a function of the host's genetic background; the same non-major histocompatibility complex genes and/or antigens which influence GVHR mortality do not influence the intensity of GVHR splenomegaly or the time of skin rejection. In contrast, the severity of GVHR mortality correlates with the intensity of stimulation in mixed lymphocyte culture. The roles of minor histocompatibility (H) antigens and Mls product are discussed.", "contents": "Graft-versus-host reaction. Influence of genetic background in donor-recipient pairs incompatible for major histocompatibility complex (MHC). In two H-2b anti-H-2d but not in H-2b anti-H2k donor-recipient combinations, graft-versus-host reaction (GVHR) mortality was found to vary as a function of the host's genetic background; the same non-major histocompatibility complex genes and/or antigens which influence GVHR mortality do not influence the intensity of GVHR splenomegaly or the time of skin rejection. In contrast, the severity of GVHR mortality correlates with the intensity of stimulation in mixed lymphocyte culture. The roles of minor histocompatibility (H) antigens and Mls product are discussed."}
{"id": "PMID:18824", "title": "[Immunosuppressive properties of vinblastine and colchicine].", "content": "The action of vinblastine and colchicine on the populations of antibody-forming cells, their precursors and stem cells using a model of primary immune response and in the transplantation system was studied using techniques by Jerne and Nordin (1963), Kennedy et al. (1965), and Till and McCulloch (1961). It was discovered that vinblastine and colchicine, at single administration 48 hours after immunization, inhibited immune response completely. The administration of colchicine and vinblastine to a donor gave an exponential decrease of in foci-forming cell number in a recipient in the system of syngenic transfer. But at the same time, vinblastine at small doses stimulated population of antibody-forming and stem cells, whereas at large doses it was not effective. Colchicine, in contrast, strongly inhibited both antibody-forming and haemopoietic cells in the recipient.", "contents": "[Immunosuppressive properties of vinblastine and colchicine]. The action of vinblastine and colchicine on the populations of antibody-forming cells, their precursors and stem cells using a model of primary immune response and in the transplantation system was studied using techniques by Jerne and Nordin (1963), Kennedy et al. (1965), and Till and McCulloch (1961). It was discovered that vinblastine and colchicine, at single administration 48 hours after immunization, inhibited immune response completely. The administration of colchicine and vinblastine to a donor gave an exponential decrease of in foci-forming cell number in a recipient in the system of syngenic transfer. But at the same time, vinblastine at small doses stimulated population of antibody-forming and stem cells, whereas at large doses it was not effective. Colchicine, in contrast, strongly inhibited both antibody-forming and haemopoietic cells in the recipient."}
{"id": "PMID:18826", "title": "[Temporary characteristics of the process of stem cell inactivation by allogenic lymphocytes].", "content": "The time during which transplated lymphocytes block proliferation and differentiation of non-syngeic stem cells has been determined by retrasplantation of immuno-competent cells from one lethally irradiated recipient to another one. It was established that process of inactivation of CFU by allogeneic lymphocytes proceeds itwo stages. At the first stage, the colonization of recipient's tissues takes place. The colonization of tissues and processes of early recognition are completed during the first hours after transplantation of cell mixtures. At the second stage, the processes of redistribution of injected cells occur and a complete inactivation of stem cells take place. These events are completed in bone marrow and spleen 4-5 days after transplantation of cells mixture, possibly with the participation of lymphocytes sensibilized with the target-cells.", "contents": "[Temporary characteristics of the process of stem cell inactivation by allogenic lymphocytes]. The time during which transplated lymphocytes block proliferation and differentiation of non-syngeic stem cells has been determined by retrasplantation of immuno-competent cells from one lethally irradiated recipient to another one. It was established that process of inactivation of CFU by allogeneic lymphocytes proceeds itwo stages. At the first stage, the colonization of recipient's tissues takes place. The colonization of tissues and processes of early recognition are completed during the first hours after transplantation of cell mixtures. At the second stage, the processes of redistribution of injected cells occur and a complete inactivation of stem cells take place. These events are completed in bone marrow and spleen 4-5 days after transplantation of cells mixture, possibly with the participation of lymphocytes sensibilized with the target-cells."}
{"id": "PMID:18828", "title": "[Physicochemical characteristics of calcium binding with plasma membranes of rabbit skeletal muscles].", "content": "It is established that Ca2+ binding with rabbit skeletal muscles plasmatic membrane depends on this cation concentration in the incubating medium. pH, temperature, incubation period and presence of Mg ions in the medium affect the Ca2+-binding ability of sarcolemma. The entropic changes observed in sarcolemma Ca2+ binding are due to conformation reconstructions of the membrane components.", "contents": "[Physicochemical characteristics of calcium binding with plasma membranes of rabbit skeletal muscles]. It is established that Ca2+ binding with rabbit skeletal muscles plasmatic membrane depends on this cation concentration in the incubating medium. pH, temperature, incubation period and presence of Mg ions in the medium affect the Ca2+-binding ability of sarcolemma. The entropic changes observed in sarcolemma Ca2+ binding are due to conformation reconstructions of the membrane components."}
{"id": "PMID:18830", "title": "[Properties of chymotrypsin proteinase from Aspergillus oryzae].", "content": "Chymotrypsin-type proteinase is detected in the proteolytic system of Asp. oryzae. The action of it and chymotrypsin is shown to depend on formaldehyde. Hydrolysis of substrates, p-nitrophenyl acetate (p-NPA) and N-benzoyl-tyrosine methyl ether (BTME), by both preparations is almost the same. The obtained activity pH-optimum for the studied proteinase esterolytic activity is located in the alkaline zone as well as for crystalline chymotrypsin (substrate p-NPA). It concerns pH of both enzymes stability as well. The enzyme under study is relatively labile. At 50 degrees C there are only traces of the activity in the medium with p-NPG. Its considerable decrease is observed at 40 degrees C. This type activity is more stable on the substrate BTME. 10 min later it disappears completely in the enzymic preparation at a temperature of 60 degrees C at 40 degrees C it is 96.8%. For 24 h at 25 degrees C the activity lowers only by 8%. Crystalline chymotrypsin is stable under these conditions. DEAE-cellulose chromatography (different types of elution) detected multiple forms of proteinase differing in solubility chromatographic properties and specific activity when splitting the substrates p-NPA, BTME and casein.", "contents": "[Properties of chymotrypsin proteinase from Aspergillus oryzae]. Chymotrypsin-type proteinase is detected in the proteolytic system of Asp. oryzae. The action of it and chymotrypsin is shown to depend on formaldehyde. Hydrolysis of substrates, p-nitrophenyl acetate (p-NPA) and N-benzoyl-tyrosine methyl ether (BTME), by both preparations is almost the same. The obtained activity pH-optimum for the studied proteinase esterolytic activity is located in the alkaline zone as well as for crystalline chymotrypsin (substrate p-NPA). It concerns pH of both enzymes stability as well. The enzyme under study is relatively labile. At 50 degrees C there are only traces of the activity in the medium with p-NPG. Its considerable decrease is observed at 40 degrees C. This type activity is more stable on the substrate BTME. 10 min later it disappears completely in the enzymic preparation at a temperature of 60 degrees C at 40 degrees C it is 96.8%. For 24 h at 25 degrees C the activity lowers only by 8%. Crystalline chymotrypsin is stable under these conditions. DEAE-cellulose chromatography (different types of elution) detected multiple forms of proteinase differing in solubility chromatographic properties and specific activity when splitting the substrates p-NPA, BTME and casein."}
{"id": "PMID:18835", "title": "Feasibility of localizing ectopic testes by 131I-labeled luteinizing hormone scintigraphy.", "content": "A new method for localizing ectopic testes preoperatively was investigated in rats. Twenty hours after administration of iodine-131 luteinizing hormone the position of normal descended testes was easily identified by scintigraphy. Clinically, this technique may offer a noninvasive and practical means of locating testes undetected by palpation. The complexity and hazards of the surgical intervention to follow would thus be greatly reduced.", "contents": "Feasibility of localizing ectopic testes by 131I-labeled luteinizing hormone scintigraphy. A new method for localizing ectopic testes preoperatively was investigated in rats. Twenty hours after administration of iodine-131 luteinizing hormone the position of normal descended testes was easily identified by scintigraphy. Clinically, this technique may offer a noninvasive and practical means of locating testes undetected by palpation. The complexity and hazards of the surgical intervention to follow would thus be greatly reduced."}
{"id": "PMID:18831", "title": "[Effect of acid anions and medium acidity on pH during a change of immunoglobulin G, peculiar to malignant growth, to water-insoluble state].", "content": "Affinity of an acid anion for proteins has a decisive effect on conditions for detecting using an acid medium immunoglobulin G peculiar to the malignant growth in blood serum of patients with cancer. Depending on the protein affinity of the anion of the acid used for the reaction immunoglobulin G appearing in blood of patients with cancer under equal conditions may be in a soluble state or change to a sediment. The presence of salts in the reaction mixture has no effect on conditions of the reaction performance. Exposition of blood sera to the acid medium before titration favours a more distinct detection of the studied protein in blood of patients with cancer.", "contents": "[Effect of acid anions and medium acidity on pH during a change of immunoglobulin G, peculiar to malignant growth, to water-insoluble state]. Affinity of an acid anion for proteins has a decisive effect on conditions for detecting using an acid medium immunoglobulin G peculiar to the malignant growth in blood serum of patients with cancer. Depending on the protein affinity of the anion of the acid used for the reaction immunoglobulin G appearing in blood of patients with cancer under equal conditions may be in a soluble state or change to a sediment. The presence of salts in the reaction mixture has no effect on conditions of the reaction performance. Exposition of blood sera to the acid medium before titration favours a more distinct detection of the studied protein in blood of patients with cancer."}
{"id": "PMID:18832", "title": "[Incorporation in vivo of 14C-precursors into pyrimidine nucleotides of chicken liver and spleen tissues].", "content": "Maximum incorporation of the label after administration of 14C-bicarbonate to free pyrimidine nucleotides begins by the 60th minute. Radioactivity of cytidine nucleotides at all time points is four-eight times as low as that of uridine nucleotides. 2-14C-orotic acid is incorporated into acid-soluble nucleotides and RNA of the liver and spleen tissues. 60 min after administration of the isotope 20% of radioactivity was found in the liver and 0.3% in the spleen, in both tissues radioactivity of RNA is 20% of 14C-radioactivity in the acid-soluble fraction. The formation rate for cytidine nucleotides from uridine ones in the liver and spleen tissues is low, about 2-6% of uridine nucleotides radioactivity is found in them only, that may be due to a low activity of CTP-synthetase. The content of cytidine nucleotides in these organs is three-life times as low as compared to uridine nucleotides.", "contents": "[Incorporation in vivo of 14C-precursors into pyrimidine nucleotides of chicken liver and spleen tissues]. Maximum incorporation of the label after administration of 14C-bicarbonate to free pyrimidine nucleotides begins by the 60th minute. Radioactivity of cytidine nucleotides at all time points is four-eight times as low as that of uridine nucleotides. 2-14C-orotic acid is incorporated into acid-soluble nucleotides and RNA of the liver and spleen tissues. 60 min after administration of the isotope 20% of radioactivity was found in the liver and 0.3% in the spleen, in both tissues radioactivity of RNA is 20% of 14C-radioactivity in the acid-soluble fraction. The formation rate for cytidine nucleotides from uridine ones in the liver and spleen tissues is low, about 2-6% of uridine nucleotides radioactivity is found in them only, that may be due to a low activity of CTP-synthetase. The content of cytidine nucleotides in these organs is three-life times as low as compared to uridine nucleotides."}
{"id": "PMID:18829", "title": "[Some mechanisms of carbohydrate metabolism regulation with NADP participation].", "content": "It is shown that in the presence of NADP in the myocardium extracts glucose-6-phosphate is transformed into fructose-6-phosphate, fructose-1,6-diphosphate and lactate. The intensity of this transformation is close to that when NAD is introduced. The addition of crystalline glucose-6-phosphate dehydrogenase to the  extracts is not accompanied by formation of lactate, but reduced NADP accumulates which oxidizes due to introduction of pyruvate or oxalacetate into the medium. This process is reconstructed in the system with pure enzymes (glucose-6-phosphate dehydrogenase, lactate dehydrogenase), that evidences for hydrogen transfer from reduced NADP to pyruvate, or to the oxalacetate without participation of transhydrogenase. The oxidation rate of the reduced coenzymes in the myocardium extracts depends on the medium pH: when pH increases, it lowers for NAD-H and rises for NAD-H. The NAD-H divided by NADP-H rate ratio at pH 7.0 for pyruvate is 11.5 and for oxalacetate is 6.5.", "contents": "[Some mechanisms of carbohydrate metabolism regulation with NADP participation]. It is shown that in the presence of NADP in the myocardium extracts glucose-6-phosphate is transformed into fructose-6-phosphate, fructose-1,6-diphosphate and lactate. The intensity of this transformation is close to that when NAD is introduced. The addition of crystalline glucose-6-phosphate dehydrogenase to the  extracts is not accompanied by formation of lactate, but reduced NADP accumulates which oxidizes due to introduction of pyruvate or oxalacetate into the medium. This process is reconstructed in the system with pure enzymes (glucose-6-phosphate dehydrogenase, lactate dehydrogenase), that evidences for hydrogen transfer from reduced NADP to pyruvate, or to the oxalacetate without participation of transhydrogenase. The oxidation rate of the reduced coenzymes in the myocardium extracts depends on the medium pH: when pH increases, it lowers for NAD-H and rises for NAD-H. The NAD-H divided by NADP-H rate ratio at pH 7.0 for pyruvate is 11.5 and for oxalacetate is 6.5."}
{"id": "PMID:18833", "title": "[Dissociation of Penicillium vitale catalase under the effect of urea and acid pH].", "content": "Conditions are studied for Penicillium vitale catalase dissociation into subunits under the effect of urea (0.7-8.5 M) and acid pH (5.0-2.0). In 8.0 M urea (pH 5.0) a molecule of the P. vitale catalase dissociates with formation of the components, the sedimentation coefficient of which is 2.4+/-0.2S, the molecular weight is 153000+/-2800. Dissociation at pH 2.2 in 4.0 M urea results in formation of components with the sedimentation coefficient 2.2+/-0.3 S. The catalase molecule dissociation under the mentioned conditions is accompanied by a loss in the enzyme activity. The results obtained show that dissociation of the P. vitale catalase molecule requires more rigid conditions than dissociation of the animal catalase. At the same time the catalase after dissociation in 8.0-8.5 M urea loses its ability to reassociation with a decrease in the urea concentration up to 0.08 M.", "contents": "[Dissociation of Penicillium vitale catalase under the effect of urea and acid pH]. Conditions are studied for Penicillium vitale catalase dissociation into subunits under the effect of urea (0.7-8.5 M) and acid pH (5.0-2.0). In 8.0 M urea (pH 5.0) a molecule of the P. vitale catalase dissociates with formation of the components, the sedimentation coefficient of which is 2.4+/-0.2S, the molecular weight is 153000+/-2800. Dissociation at pH 2.2 in 4.0 M urea results in formation of components with the sedimentation coefficient 2.2+/-0.3 S. The catalase molecule dissociation under the mentioned conditions is accompanied by a loss in the enzyme activity. The results obtained show that dissociation of the P. vitale catalase molecule requires more rigid conditions than dissociation of the animal catalase. At the same time the catalase after dissociation in 8.0-8.5 M urea loses its ability to reassociation with a decrease in the urea concentration up to 0.08 M."}
{"id": "PMID:18836", "title": "[Changes in enzyme activity induced by experimental aflatoxicosis in dairy cows].", "content": "The activities of GOT, GPT, LDH, gamma-glutamyltranspeptidase (gamma-GTP), alkaline phosphatase (AP), glutamate dehydrogenase (GLDH) and the concentrations of bilirubin in blood plasma after a single intraruminal application of aflatoxins were studied in four dairy cows. The maximum changes in the activities of the enzymes and the maximum bilirubin concentration in plasma were obtained in the first two to three days following the application of aflatoxins. The statistically significant increase of GOT activity, compared with activity before the application of aflatoxins, persisted until the 23rd day; in the case of LDH and GLDH the increase persisted until the 38th day from the application of aflatoxins. The activities of gamma-GTP and AP were slightly higher even on the 50th day. The increased concentration of bilirubin in plasma lasted until the 23rd day from aflatoxin application. The increased activities of enzymes testify to an impaired function of the liver, which is also proved by the specific enzymes GLDH, gamma-GTP, by increased bilirubin levels, and by histological changes known from literature. The evaluation of enzymatic activities and bilirubin concentration in plasma can make a valuable contribution to correct diagnosis of aflatoxicoses in cattle.", "contents": "[Changes in enzyme activity induced by experimental aflatoxicosis in dairy cows]. The activities of GOT, GPT, LDH, gamma-glutamyltranspeptidase (gamma-GTP), alkaline phosphatase (AP), glutamate dehydrogenase (GLDH) and the concentrations of bilirubin in blood plasma after a single intraruminal application of aflatoxins were studied in four dairy cows. The maximum changes in the activities of the enzymes and the maximum bilirubin concentration in plasma were obtained in the first two to three days following the application of aflatoxins. The statistically significant increase of GOT activity, compared with activity before the application of aflatoxins, persisted until the 23rd day; in the case of LDH and GLDH the increase persisted until the 38th day from the application of aflatoxins. The activities of gamma-GTP and AP were slightly higher even on the 50th day. The increased concentration of bilirubin in plasma lasted until the 23rd day from aflatoxin application. The increased activities of enzymes testify to an impaired function of the liver, which is also proved by the specific enzymes GLDH, gamma-GTP, by increased bilirubin levels, and by histological changes known from literature. The evaluation of enzymatic activities and bilirubin concentration in plasma can make a valuable contribution to correct diagnosis of aflatoxicoses in cattle."}
{"id": "PMID:18837", "title": "[Chronic metabolic acidosis in dairy cows].", "content": "Complex clinical and clinico-biochemical examination of the blood, urine and rumen liquor in a herd of dairy cows revealed chronical metabolic acidosis accompanied by rumen dysfunction and by a reduced butterfat content of milk. During the first examination of the acid-base state of the blood was almost at a standard level. An increased level of urea in blood plasma and a higher GOT transaminase activity testified to an excessive load on the liver. Urine pH was considerably deviated towards the acidic side and inorganic phosphorus was present in urine in a greater concentration. The pH of rumen liquor was slightly shifted towards alkalinity owing to the release of NH3 from urea in the food ration. The diagnosis--suspect chronical metabolic acidosis--was determined on the basis of the first examination. Chronical metabolic acidosis was definitely proved by the second examination when urea had been excluded from the feed ration. Repeated examinations revealed chronical metabolic acidosis which had originally been accompanied by a higher rumen liquor pH. On the basis of case histories and mechanisms of chronical acidosis, measures were proposed, resulting in an increase of the butterfat content of milk. Chronical metabolic disorders often follow a long-lasting latent pattern, manifesting themselves as a reduced milk yield and lower resistance; the clinical form of disease appears only at a later stage. The system of preventive diagnostics provides information on the changes in the composition of internal medium and of the faeces before a drop occurs in milk and fat production. These measures prevent metabolic disorders and high losses of produce which otherwise remain hidden for a long time.", "contents": "[Chronic metabolic acidosis in dairy cows]. Complex clinical and clinico-biochemical examination of the blood, urine and rumen liquor in a herd of dairy cows revealed chronical metabolic acidosis accompanied by rumen dysfunction and by a reduced butterfat content of milk. During the first examination of the acid-base state of the blood was almost at a standard level. An increased level of urea in blood plasma and a higher GOT transaminase activity testified to an excessive load on the liver. Urine pH was considerably deviated towards the acidic side and inorganic phosphorus was present in urine in a greater concentration. The pH of rumen liquor was slightly shifted towards alkalinity owing to the release of NH3 from urea in the food ration. The diagnosis--suspect chronical metabolic acidosis--was determined on the basis of the first examination. Chronical metabolic acidosis was definitely proved by the second examination when urea had been excluded from the feed ration. Repeated examinations revealed chronical metabolic acidosis which had originally been accompanied by a higher rumen liquor pH. On the basis of case histories and mechanisms of chronical acidosis, measures were proposed, resulting in an increase of the butterfat content of milk. Chronical metabolic disorders often follow a long-lasting latent pattern, manifesting themselves as a reduced milk yield and lower resistance; the clinical form of disease appears only at a later stage. The system of preventive diagnostics provides information on the changes in the composition of internal medium and of the faeces before a drop occurs in milk and fat production. These measures prevent metabolic disorders and high losses of produce which otherwise remain hidden for a long time."}
{"id": "PMID:18838", "title": "[Significance of ruminal juice examination in the diagnosis of subclinical rumen dysfunction].", "content": "The suitability of the metabolic test of rumen liquor for the diagnosis of subclinical rumen dysfunction was tested. The test for the assessment of the metabolic profile of the rumen included: the determination of pH, total titration acidity in clinical units, lactic acid in mg%, fatty acids in mmol 1-1, ammonia N in mg%, urea N in mg% and the number of infusorians in 1 ml of rumen liquor. This test enabled, on the basis of the examination of rumen liquor, to determine not only the kind and form of the disease but also its cause, with an incomplete clinical syndrome. Therapeutic measures, either direct (in the rumen liquor) or indirect (adjusted monodiet) improved the health condition and provided optimum rumen fermentation of permanent character. The resuption of rumen fermentation also enabled an increased production of fatty acids which favourably influenced the content of butterfat in milk.", "contents": "[Significance of ruminal juice examination in the diagnosis of subclinical rumen dysfunction]. The suitability of the metabolic test of rumen liquor for the diagnosis of subclinical rumen dysfunction was tested. The test for the assessment of the metabolic profile of the rumen included: the determination of pH, total titration acidity in clinical units, lactic acid in mg%, fatty acids in mmol 1-1, ammonia N in mg%, urea N in mg% and the number of infusorians in 1 ml of rumen liquor. This test enabled, on the basis of the examination of rumen liquor, to determine not only the kind and form of the disease but also its cause, with an incomplete clinical syndrome. Therapeutic measures, either direct (in the rumen liquor) or indirect (adjusted monodiet) improved the health condition and provided optimum rumen fermentation of permanent character. The resuption of rumen fermentation also enabled an increased production of fatty acids which favourably influenced the content of butterfat in milk."}
{"id": "PMID:18843", "title": "HLA-antibody-induced 14C-serotonin release from platelets. A methodological analysis.", "content": "The prerequisites and kinetics of HLA-antibody-induced 14C-serotonin release from platelets were investigated with five HLA-specific antisera. By studying the influence of incubation time, temperature, pH, platelet count, stirring and extent of platelet labeling, optimal results were obtained after 30 (to 60) min of incubation at 37 degrees C, pH 7.5-8.0, under constant stirring (400 rpm). Optimal platelet counts varied between 160,000 and 400,000/microliter depending on the antiserum applied. A comparison of the amount of 14C-serotonin released by different antisera from washed platelets and from platelets in platelet-rich plasma suggests that plasma components--most likely complement--may additionally influence the results. Based on these experiments, a standardized microtechnique of HLA-antibody-induced 14C-serotonin release is recommended.", "contents": "HLA-antibody-induced 14C-serotonin release from platelets. A methodological analysis. The prerequisites and kinetics of HLA-antibody-induced 14C-serotonin release from platelets were investigated with five HLA-specific antisera. By studying the influence of incubation time, temperature, pH, platelet count, stirring and extent of platelet labeling, optimal results were obtained after 30 (to 60) min of incubation at 37 degrees C, pH 7.5-8.0, under constant stirring (400 rpm). Optimal platelet counts varied between 160,000 and 400,000/microliter depending on the antiserum applied. A comparison of the amount of 14C-serotonin released by different antisera from washed platelets and from platelets in platelet-rich plasma suggests that plasma components--most likely complement--may additionally influence the results. Based on these experiments, a standardized microtechnique of HLA-antibody-induced 14C-serotonin release is recommended."}
{"id": "PMID:18839", "title": "[Electrophoretic and kinetic properties of the erythrocyte glucose-6-phosphate dehydrogenase of patients with hemolytic anemia related to a deficit in the activity of that enzyme].", "content": "Partially purified glucose-6-phosphate dehydrogenase (G6PD) was studied in erythrocytes of patients with hereditary hemolytic anemia. Kinetic and electrophoretic properties of G6PD distinctly varied both in patients--homozygotes and in maternal heterozygotes. All the enzymes studied together with the decreased activity possessed the reduced Km value for NADP and G6P. Anomalous enzymes were shown to differ from normal ones by several patterns (pH-dependency, thermostability, % of the substrate analogues utilization, electrophoretic mobility etc). The mutant variant of G6PD was not described earlier. The anomalies variant was called \"Kremenchug\" to indicate the place of proband origination.", "contents": "[Electrophoretic and kinetic properties of the erythrocyte glucose-6-phosphate dehydrogenase of patients with hemolytic anemia related to a deficit in the activity of that enzyme]. Partially purified glucose-6-phosphate dehydrogenase (G6PD) was studied in erythrocytes of patients with hereditary hemolytic anemia. Kinetic and electrophoretic properties of G6PD distinctly varied both in patients--homozygotes and in maternal heterozygotes. All the enzymes studied together with the decreased activity possessed the reduced Km value for NADP and G6P. Anomalous enzymes were shown to differ from normal ones by several patterns (pH-dependency, thermostability, % of the substrate analogues utilization, electrophoretic mobility etc). The mutant variant of G6PD was not described earlier. The anomalies variant was called \"Kremenchug\" to indicate the place of proband origination."}
{"id": "PMID:18841", "title": "[Purification and several properties of thiamine pyrophosphokinase from rat liver].", "content": "Thiamin pyrophosphokinase (TPK) (EC 2.7.6.2) was isolated and purified from rat liver tissue ion in exchange chromatography, rechromatography and gel filtration. The enzyme was purified 3000-fold with yield of 12%, it was homogenous in polyacrylamide gel disc electrophoresis. TPK had two pH optima; Km value for thiamin was equal to 6-10(-6) M. Pyrithiamin was shown to be a competitive inhibitor with K1=3-10(-6) M and hydroxythiamin--an inhibitor of the mixed type with K1=1-10(-2) M. The relationship between the rate of the reaction and the substrate concentration (ATP-Mg2+) at the Mg2+/ATP ratio of 1:1 was described by S-like curve, which acquired a hyprebolic form in presence of an excess of Mg2+. Dependence of the reaction rate on Mg2+ concentration was also described by a sigmoid curve. The data obtained suggest that liver TPK was apparently an allosteric enzyme with quaternary structure.", "contents": "[Purification and several properties of thiamine pyrophosphokinase from rat liver]. Thiamin pyrophosphokinase (TPK) (EC 2.7.6.2) was isolated and purified from rat liver tissue ion in exchange chromatography, rechromatography and gel filtration. The enzyme was purified 3000-fold with yield of 12%, it was homogenous in polyacrylamide gel disc electrophoresis. TPK had two pH optima; Km value for thiamin was equal to 6-10(-6) M. Pyrithiamin was shown to be a competitive inhibitor with K1=3-10(-6) M and hydroxythiamin--an inhibitor of the mixed type with K1=1-10(-2) M. The relationship between the rate of the reaction and the substrate concentration (ATP-Mg2+) at the Mg2+/ATP ratio of 1:1 was described by S-like curve, which acquired a hyprebolic form in presence of an excess of Mg2+. Dependence of the reaction rate on Mg2+ concentration was also described by a sigmoid curve. The data obtained suggest that liver TPK was apparently an allosteric enzyme with quaternary structure."}
{"id": "PMID:18842", "title": "[Immunochemical characteristics of hydrocortisone induced and hydrocortisone non-induced rat liver tyrosine aminotransferase isoenzymes].", "content": "Two isoenzymes of tyrosine aminotransferase (induced and noninduced by hydrocortisone were isolated from rat liver tissue and subjected to chromatographic purification. Specific antibodies with high titer were obtained after immunization of rabbits by the inducible isoenzyme. The antigenic properties of the obtained tyrosine aminotransferase isoenzymes were compared after double immunodiffusion in agar and immunoelectrophoresis. The purified induced and non-induced isoenzymes were shown to possess both similar and different antigenic determinants. The data obtained suggest that differences in antigenic properties of the tyrosine aminotransferase isoenzymes reflect those variations in their structure, which are expressed as various thermostability, sensitivity to proteolytic enzymes and substrate specificity.", "contents": "[Immunochemical characteristics of hydrocortisone induced and hydrocortisone non-induced rat liver tyrosine aminotransferase isoenzymes]. Two isoenzymes of tyrosine aminotransferase (induced and noninduced by hydrocortisone were isolated from rat liver tissue and subjected to chromatographic purification. Specific antibodies with high titer were obtained after immunization of rabbits by the inducible isoenzyme. The antigenic properties of the obtained tyrosine aminotransferase isoenzymes were compared after double immunodiffusion in agar and immunoelectrophoresis. The purified induced and non-induced isoenzymes were shown to possess both similar and different antigenic determinants. The data obtained suggest that differences in antigenic properties of the tyrosine aminotransferase isoenzymes reflect those variations in their structure, which are expressed as various thermostability, sensitivity to proteolytic enzymes and substrate specificity."}
{"id": "PMID:18846", "title": "Contamination of rat urine with gut flora using all-glass metabolism cages for collection of urine and faeces.", "content": "In rat urine collected in all-glass metabolism cages, at least four strains of intestinal microflora were found: two types of E. coli, Enterobacter cloaceae and Proteus vulgaris. The number of bacteria of each strain increased with time. 2. The pH of the urine increased from 6-9 after 24 h to 8-95 after 120 h. The pH of the urine of neomycin-treated rats remained nearly constant over a period of two days. 3. Nitroreductase activity was present in the rat urine. Added p-nitrobenzoic acid was reduced within the first 24 h. Nitroreductase activity in the urine of neomycin-treated rats was significantly lower than in the urine of normal rats, during the second 24-h period only. 4. Collection of urine at -10 degrees prevented the consequences of contamination.", "contents": "Contamination of rat urine with gut flora using all-glass metabolism cages for collection of urine and faeces. In rat urine collected in all-glass metabolism cages, at least four strains of intestinal microflora were found: two types of E. coli, Enterobacter cloaceae and Proteus vulgaris. The number of bacteria of each strain increased with time. 2. The pH of the urine increased from 6-9 after 24 h to 8-95 after 120 h. The pH of the urine of neomycin-treated rats remained nearly constant over a period of two days. 3. Nitroreductase activity was present in the rat urine. Added p-nitrobenzoic acid was reduced within the first 24 h. Nitroreductase activity in the urine of neomycin-treated rats was significantly lower than in the urine of normal rats, during the second 24-h period only. 4. Collection of urine at -10 degrees prevented the consequences of contamination."}
{"id": "PMID:18847", "title": "[Influence of the age of old primiparae on the perinatal infant morbidity and mortility (author's transl)].", "content": "157 old primiparae (greater than 30 a) have been compared to a randomised control group of primiparae between the 16th and 30th year of age. In addition to the perinatal infant mortality rate, the number of children with malnutrition, the frequency of premature babies, the presence of a low Apgar score (less than or equal to 7) and pathological pH-values in the umbilical artery (pH less than or equal to 7,10) were cheked. Moreover the frequency of early neonatal morbidity (presence of one of the following criteria: 1 minute Apgar score less than or equal to 7, pH of the umbilical artery less than or equal to 7, 10, a transitoric or severe RDS and neurological complications during the newborn period) was investigated in both groups. In the group of the old primiparae a significantly higher perinatal infant mortality rate was found compared to the control group (3,8% versus 0,6%, p less than 0.05). The rate of small for date babies was remarcably higher than in the control group (14,6% versus 6,4%, p less than 0.05). There was no difference in the prematurity rate in both groups. The children of old primiparae had more frequently a low Apgar score (less than or equal to 7) than infants of the randomised control group (18,5% versus 11,5%), but the difference is statistically not significant. Furthermore no difference in the number of pathological pH values in the umbilical arteries (pH less than or equal to 7, 10) were found in the both groups. The children of old primiparae show a higher early neonatal morbidity rate compared to the control group (21.7% versus 14.0%); however, the difference is statistically not significant. According to our results the risk for the newborns is increased already with primiparae over 30 rather than 35 years of age.", "contents": "[Influence of the age of old primiparae on the perinatal infant morbidity and mortility (author's transl)]. 157 old primiparae (greater than 30 a) have been compared to a randomised control group of primiparae between the 16th and 30th year of age. In addition to the perinatal infant mortality rate, the number of children with malnutrition, the frequency of premature babies, the presence of a low Apgar score (less than or equal to 7) and pathological pH-values in the umbilical artery (pH less than or equal to 7,10) were cheked. Moreover the frequency of early neonatal morbidity (presence of one of the following criteria: 1 minute Apgar score less than or equal to 7, pH of the umbilical artery less than or equal to 7, 10, a transitoric or severe RDS and neurological complications during the newborn period) was investigated in both groups. In the group of the old primiparae a significantly higher perinatal infant mortality rate was found compared to the control group (3,8% versus 0,6%, p less than 0.05). The rate of small for date babies was remarcably higher than in the control group (14,6% versus 6,4%, p less than 0.05). There was no difference in the prematurity rate in both groups. The children of old primiparae had more frequently a low Apgar score (less than or equal to 7) than infants of the randomised control group (18,5% versus 11,5%), but the difference is statistically not significant. Furthermore no difference in the number of pathological pH values in the umbilical arteries (pH less than or equal to 7, 10) were found in the both groups. The children of old primiparae show a higher early neonatal morbidity rate compared to the control group (21.7% versus 14.0%); however, the difference is statistically not significant. According to our results the risk for the newborns is increased already with primiparae over 30 rather than 35 years of age."}
{"id": "PMID:18848", "title": "[Pharmacokinetic of piracetam during labour influence to acid-base-status in maternal and fetal blood (author's transl)].", "content": "PIRACETAM concentrations in fetal and maternal blood were measured during the first and second stage of labor and the elimination in maternal and fetal blood was studied. Fetal heart-rate, pH- and base-excess of the maternal and fetal blood were investigated to evaluate the influence of PIRACETAM on the acid-base-status of mother and child. PIRACETAM was administered intravenously to 43 patients in a dosage 2 g, 4 g and 6 g. The concentration in the maternal and fetal plasma was measured by gaschromatography. Before and after the injection of PIRACETAM and at delivery, blood was sampled from the mother's earlobe and the umbilical artery and vein, respectively. The results were compared with a control group. There was an exponential fall of PIRACETAM concentration in maternal and fetal blood. Maternal and fetal elimination half-life of PIRACETAM was about 112-98 minutes and 200 minutes, respectively. A fairly good correlation between the concentration of PIRACETAM in maternal and fetal blood was found. The fetal PIRACETAM concentration was about 50% below the maternal values. Fetal heart-rate, maternal and fetal pH- and base-excess-values were not significantly altered following PIRACETAM infusion. It may be concluded, that there exists a transfer of PIRACETAM across the placental barrier. However, the cytoprotective effect of PIRACETAM, as described in animal observations and by investigations in human, could not be verified by the methods and technology used in this study.", "contents": "[Pharmacokinetic of piracetam during labour influence to acid-base-status in maternal and fetal blood (author's transl)]. PIRACETAM concentrations in fetal and maternal blood were measured during the first and second stage of labor and the elimination in maternal and fetal blood was studied. Fetal heart-rate, pH- and base-excess of the maternal and fetal blood were investigated to evaluate the influence of PIRACETAM on the acid-base-status of mother and child. PIRACETAM was administered intravenously to 43 patients in a dosage 2 g, 4 g and 6 g. The concentration in the maternal and fetal plasma was measured by gaschromatography. Before and after the injection of PIRACETAM and at delivery, blood was sampled from the mother's earlobe and the umbilical artery and vein, respectively. The results were compared with a control group. There was an exponential fall of PIRACETAM concentration in maternal and fetal blood. Maternal and fetal elimination half-life of PIRACETAM was about 112-98 minutes and 200 minutes, respectively. A fairly good correlation between the concentration of PIRACETAM in maternal and fetal blood was found. The fetal PIRACETAM concentration was about 50% below the maternal values. Fetal heart-rate, maternal and fetal pH- and base-excess-values were not significantly altered following PIRACETAM infusion. It may be concluded, that there exists a transfer of PIRACETAM across the placental barrier. However, the cytoprotective effect of PIRACETAM, as described in animal observations and by investigations in human, could not be verified by the methods and technology used in this study."}
{"id": "PMID:18849", "title": "Studies on in vitro survival of Isoparorchis hypselobagri.", "content": "Adult parasites, Isoparorchis hypselobagri were maintained in vitro in four basic salt solutions, viz. Stephenson saline, AB saline, Tyrode's solution and Locke's solution. Survival was prolonged by adding sugars to Tyrode's solution. Of all the sugars, glucose was found most effective and parasites survived for 39 days in solution containing glucose, 6 days in galactose and sucrose, 10 days in fructose and lactose and 12 days in maltose. The parasites absorb carbohydrates through the cuticle. Ligated parasites survived for a longer period than unligated parasites. The pH 9 was considered as an optimum for maximum survival of the parasites Isoparorchis hypselobagri for 39 days.", "contents": "Studies on in vitro survival of Isoparorchis hypselobagri. Adult parasites, Isoparorchis hypselobagri were maintained in vitro in four basic salt solutions, viz. Stephenson saline, AB saline, Tyrode's solution and Locke's solution. Survival was prolonged by adding sugars to Tyrode's solution. Of all the sugars, glucose was found most effective and parasites survived for 39 days in solution containing glucose, 6 days in galactose and sucrose, 10 days in fructose and lactose and 12 days in maltose. The parasites absorb carbohydrates through the cuticle. Ligated parasites survived for a longer period than unligated parasites. The pH 9 was considered as an optimum for maximum survival of the parasites Isoparorchis hypselobagri for 39 days."}
{"id": "PMID:18858", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. XI. Influence of heating and freezing (author's transl)].", "content": "The tripolyphosphatase and diphosphatase activities of comminuted bovine muscle increase with rising temperature until at about 40 degrees C a denaturation of the enzyme proteins occurs. Prae or post rigor frozen bovine muscle, which was stored at -18 degrees C, shows after thawing and mincing the same tripolyphosphatase activity as the non-frozen tissue post rigor. Freezing and thawing under the same conditions cause a reversible inhibition of the  diphosphatase activity of bovine muscle. The reactivation depends on the pH. This inhibition is probably identical with that occurring during storage of beef at -4 degrees C.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. XI. Influence of heating and freezing (author's transl)]. The tripolyphosphatase and diphosphatase activities of comminuted bovine muscle increase with rising temperature until at about 40 degrees C a denaturation of the enzyme proteins occurs. Prae or post rigor frozen bovine muscle, which was stored at -18 degrees C, shows after thawing and mincing the same tripolyphosphatase activity as the non-frozen tissue post rigor. Freezing and thawing under the same conditions cause a reversible inhibition of the  diphosphatase activity of bovine muscle. The reactivation depends on the pH. This inhibition is probably identical with that occurring during storage of beef at -4 degrees C."}
{"id": "PMID:18859", "title": "[Formation of dehydroalanine, lanthionine and lysinoalanine during heat treatment of beta-lactoglobuline A (author's transl)].", "content": "Solutions of beta-lactoglobulin A were heated at 97.5 degrees C at pH 6.9 and 9.8 80 min. The formation of dehydroalanine, lanthionine and lysinoalanine as well as changes in the levels of cysteine, cystine and the basic amino acids were recorded. Lanthionine (equal amounts of the 1- and the mesoform) was formed only in small amounts, while the lysinoalanine levels were rather high. Beside this, lysine was converted to unknown compounds. The main sources for the formation of dehydroalanine are the cystine moieties of the protein. Cysteine residues are first oxidized to cystine before beta-elimination occurs.", "contents": "[Formation of dehydroalanine, lanthionine and lysinoalanine during heat treatment of beta-lactoglobuline A (author's transl)]. Solutions of beta-lactoglobulin A were heated at 97.5 degrees C at pH 6.9 and 9.8 80 min. The formation of dehydroalanine, lanthionine and lysinoalanine as well as changes in the levels of cysteine, cystine and the basic amino acids were recorded. Lanthionine (equal amounts of the 1- and the mesoform) was formed only in small amounts, while the lysinoalanine levels were rather high. Beside this, lysine was converted to unknown compounds. The main sources for the formation of dehydroalanine are the cystine moieties of the protein. Cysteine residues are first oxidized to cystine before beta-elimination occurs."}
{"id": "PMID:18861", "title": "[Detection and quantitative estimation of 2,2-diethyl-4-pentenamide in a fatal case of poisoning (author's transl)].", "content": "Toxicological investivation in a fatal case of poisoning by Novo-DolestanR and DoromaR is presented with methods for identification and quantitative estimation of 2,2-diethyl-4-pentenamide especially. The findings confirm 2,2-diethyl-4-pentenamide as the main toxic agent in this case.", "contents": "[Detection and quantitative estimation of 2,2-diethyl-4-pentenamide in a fatal case of poisoning (author's transl)]. Toxicological investivation in a fatal case of poisoning by Novo-DolestanR and DoromaR is presented with methods for identification and quantitative estimation of 2,2-diethyl-4-pentenamide especially. The findings confirm 2,2-diethyl-4-pentenamide as the main toxic agent in this case."}
{"id": "PMID:18863", "title": "[Evaluation of congenital-cryptorchid testicles after surgical treatment (author's transl)].", "content": "The volume of 271 congenital-cryptorchid testicles which were subject to surgical treatment was compared with that of 128 descended testicles of patients of the same age. Undescended testicles, also after successful surgical treatment, remain smaller on volume than descended ones. By means of the hitting method of the point counting technique the proportion of all seminiferous tubules in the total volume of one gonad can be calculated. The seminiferous tubules of congenital-cryptorchid testicles, also after intrascrotal replacement, maintain an essentially smaller proportion concerning the total volume as in descended testicles. Among the numerous methods of surgical treatment preference must be given to those which are especially favourable to the parenchyma.", "contents": "[Evaluation of congenital-cryptorchid testicles after surgical treatment (author's transl)]. The volume of 271 congenital-cryptorchid testicles which were subject to surgical treatment was compared with that of 128 descended testicles of patients of the same age. Undescended testicles, also after successful surgical treatment, remain smaller on volume than descended ones. By means of the hitting method of the point counting technique the proportion of all seminiferous tubules in the total volume of one gonad can be calculated. The seminiferous tubules of congenital-cryptorchid testicles, also after intrascrotal replacement, maintain an essentially smaller proportion concerning the total volume as in descended testicles. Among the numerous methods of surgical treatment preference must be given to those which are especially favourable to the parenchyma."}
{"id": "PMID:18864", "title": "Accentuation of Staphylococcal hemolysis (CAMP-like test) by pneumococci.", "content": "A CAMP-like phenomenon can be observed in Streptococcus pneumoniae. It is supposed to be caused likewise as in group B streptococci by a haemolysis accentuating factor. However, the form of the accentuated haemolysis is different from that in group B streptococci and similar to that in listeria.", "contents": "Accentuation of Staphylococcal hemolysis (CAMP-like test) by pneumococci. A CAMP-like phenomenon can be observed in Streptococcus pneumoniae. It is supposed to be caused likewise as in group B streptococci by a haemolysis accentuating factor. However, the form of the accentuated haemolysis is different from that in group B streptococci and similar to that in listeria."}
{"id": "PMID:18867", "title": "A catalogue of isohormones of human growth hormone based on quantitative polyacrylamide gel electrophoresis.", "content": "With the growing recognition that all polypeptide hormones exist in heterogeneous forms, i.e., isohormones, this study represents the initial development of a comprehensive catalogue of the various isohormone species of human growth hormone (hGH) in relation to molecular structure. The catalogue is based primarily on results obtained in quantitative polyacrylamide gel electrophoresis (PAGE) in a multiphasic buffer system optimized for characterization of hGH. Thus, hGH forms can be recognized in objective, numerical terms based on physicochemical parameters of molecular size and net charge. Isoelectric focusing in polyacrylamide gel; and PAGE in sodium dodecyl sulphate in the presence and absence of reducing agents supplement the quantitative PAGE criteria. Specific hGH immunoreactivity is necessary to completely distinguish hGH from hormones of similar size and charge properties (prolactin and chorionic somatomammotrophin). In the examination of eight standard hGH preparations obtained from four laboratories, all preparations exhibited multiple isohormone species, from two to five components per preparation. These identifiable components appear to represent the predominant species of a bidirectional continuum of hGH components, the continuum being in regard to both molecular size and charge. Within any given preparations, the continuum presents itself as a series of identifiable \"charge isomers\". Between preparations, in addition, there are size differences as well, which may relate to conformational changes (unfolding) in some preparations.", "contents": "A catalogue of isohormones of human growth hormone based on quantitative polyacrylamide gel electrophoresis. With the growing recognition that all polypeptide hormones exist in heterogeneous forms, i.e., isohormones, this study represents the initial development of a comprehensive catalogue of the various isohormone species of human growth hormone (hGH) in relation to molecular structure. The catalogue is based primarily on results obtained in quantitative polyacrylamide gel electrophoresis (PAGE) in a multiphasic buffer system optimized for characterization of hGH. Thus, hGH forms can be recognized in objective, numerical terms based on physicochemical parameters of molecular size and net charge. Isoelectric focusing in polyacrylamide gel; and PAGE in sodium dodecyl sulphate in the presence and absence of reducing agents supplement the quantitative PAGE criteria. Specific hGH immunoreactivity is necessary to completely distinguish hGH from hormones of similar size and charge properties (prolactin and chorionic somatomammotrophin). In the examination of eight standard hGH preparations obtained from four laboratories, all preparations exhibited multiple isohormone species, from two to five components per preparation. These identifiable components appear to represent the predominant species of a bidirectional continuum of hGH components, the continuum being in regard to both molecular size and charge. Within any given preparations, the continuum presents itself as a series of identifiable \"charge isomers\". Between preparations, in addition, there are size differences as well, which may relate to conformational changes (unfolding) in some preparations."}
{"id": "PMID:18866", "title": "[Alteration of several indices of carbohydrate metabolism in the blood and cerebrospinal fluid following surgery on patients with intracranial aneurysms].", "content": "The content of the lactic acid (LA) and pyruvic acid (PA) was determined pre- and postoperatively in the arterial blood and CSF of 31 patients with intracranial aneurysms. A considerable elevation of the concentration of LA and PA was noted along with an increasing LA/PA in the CSF of patients with symptoms of ischaemic damage of the brain. During surgery under fluothane narcosis these patients also demonstrated a distinct elevation of the LA level along with an increasing LA/PA ratio. In the CSF the growing content of glycolysis metabolites was not accompanied by LA/PA changes. The employment of artificial hypotension had no important effect upon the changes of these parameters in the CSF.", "contents": "[Alteration of several indices of carbohydrate metabolism in the blood and cerebrospinal fluid following surgery on patients with intracranial aneurysms]. The content of the lactic acid (LA) and pyruvic acid (PA) was determined pre- and postoperatively in the arterial blood and CSF of 31 patients with intracranial aneurysms. A considerable elevation of the concentration of LA and PA was noted along with an increasing LA/PA in the CSF of patients with symptoms of ischaemic damage of the brain. During surgery under fluothane narcosis these patients also demonstrated a distinct elevation of the LA level along with an increasing LA/PA ratio. In the CSF the growing content of glycolysis metabolites was not accompanied by LA/PA changes. The employment of artificial hypotension had no important effect upon the changes of these parameters in the CSF."}
{"id": "PMID:18876", "title": "[Behavior therapy and neurotic behavior].", "content": "The first part of the lecture presents three classical aspects of behavior therapy: therapeutic efficiency, utilisation of well defined methods, rapidity of treatment. Emphasis is brought to the importance of behavior analysis and to the dangers arisen from insufficient knowledge or ignorance of learning theories and fundamental principles of behavior analysis. One insists on experimental analysis which is the basis for methods of action having as consequence for the therapeut: controlling strategy of treatment and direct responsibility concerning success and failure. Then, actual limitations of behaviour therapy are described. The second part deals with one of the most important working hypothesis on human neurosis originating from laboratory and clinical research. Behavior therapy refuses to elaborate hypothetical deductive constructions, unless working hypotheses to be verified. Then the four essential clues to behavioural psychotherapy are formulated. The main methods of action presently utilized are presented: aversive methods, operational and systematic desensitization technics through reciprocal inhibition. Finally, some of the main criticism usually made on behaviour therapy are being discussed.", "contents": "[Behavior therapy and neurotic behavior]. The first part of the lecture presents three classical aspects of behavior therapy: therapeutic efficiency, utilisation of well defined methods, rapidity of treatment. Emphasis is brought to the importance of behavior analysis and to the dangers arisen from insufficient knowledge or ignorance of learning theories and fundamental principles of behavior analysis. One insists on experimental analysis which is the basis for methods of action having as consequence for the therapeut: controlling strategy of treatment and direct responsibility concerning success and failure. Then, actual limitations of behaviour therapy are described. The second part deals with one of the most important working hypothesis on human neurosis originating from laboratory and clinical research. Behavior therapy refuses to elaborate hypothetical deductive constructions, unless working hypotheses to be verified. Then the four essential clues to behavioural psychotherapy are formulated. The main methods of action presently utilized are presented: aversive methods, operational and systematic desensitization technics through reciprocal inhibition. Finally, some of the main criticism usually made on behaviour therapy are being discussed."}
{"id": "PMID:18875", "title": "[Behavior therapy of fear of flying in professional pilots].", "content": "The theorical frame proposed by behaviour principles seems to have an explanatory value in the genesis of some troubles of traumatic origin. This is the case for fear of flying which can appear suddenly in airline personnel following accidents, troubles or problems while flying and which could bring a definitive incapacity of flying. The use of behaviour therapy, like systematic desensibilisation, is then being considered. It is illustrated by examples taken from the literature and by two clinical cases.", "contents": "[Behavior therapy of fear of flying in professional pilots]. The theorical frame proposed by behaviour principles seems to have an explanatory value in the genesis of some troubles of traumatic origin. This is the case for fear of flying which can appear suddenly in airline personnel following accidents, troubles or problems while flying and which could bring a definitive incapacity of flying. The use of behaviour therapy, like systematic desensibilisation, is then being considered. It is illustrated by examples taken from the literature and by two clinical cases."}
{"id": "PMID:18877", "title": "[Schultz autogenic training and galvanic skin response in the systematic desensitization of a compulsive phobia].", "content": "A patient suffering suicidal phobia and resistant to antidepressants as well as electroconvulsive therapy was submitted to Wolpe's systematic desensitization associated with Schult's autogenic training. Ten sessions were sufficient to cure the patient. A follow-up period now extends to one year, without relapse. The concomitent measure of skin galvanic response by an electrodermograph appears a privileged psychophysiological control of such a therapy, i.a. allowing for detection of the avoidance of the anxiogenic evocation by the patient.", "contents": "[Schultz autogenic training and galvanic skin response in the systematic desensitization of a compulsive phobia]. A patient suffering suicidal phobia and resistant to antidepressants as well as electroconvulsive therapy was submitted to Wolpe's systematic desensitization associated with Schult's autogenic training. Ten sessions were sufficient to cure the patient. A follow-up period now extends to one year, without relapse. The concomitent measure of skin galvanic response by an electrodermograph appears a privileged psychophysiological control of such a therapy, i.a. allowing for detection of the avoidance of the anxiogenic evocation by the patient."}
{"id": "PMID:18914", "title": "Syntheses of virus-induced thymidine kinase and viral DNA in herpes simplex type 1 virus-infected chick embryo fibroblasts.", "content": "Herpes simplex virus type 1, strain Kupka, did not replicate in chick embryo fibroblasts (CEF), but the infection was followed by the development of cytopathic changes. This effect could be abolished by UV irradiation of the virus. Virus-induced thymidine kinase was synthesized in the infected cells reaching a maximum level at 24 hours post infection (p.i.). In the presence of cytosine arabinoside, thymidine kinase synthesis was enhanced. This suggested that the late (post-replicative) viral function, which turns off thymidine kinase synthesis, was expressed in the infected CEF untreated with the drug. HSV type 1 laboratory strains Kupka and KOS were capable of inducing the synthesis of virus-specific DNA in CEF. But in CEF infected with fresh type 1 virus isolates replication of viral DNA was not observed.", "contents": "Syntheses of virus-induced thymidine kinase and viral DNA in herpes simplex type 1 virus-infected chick embryo fibroblasts. Herpes simplex virus type 1, strain Kupka, did not replicate in chick embryo fibroblasts (CEF), but the infection was followed by the development of cytopathic changes. This effect could be abolished by UV irradiation of the virus. Virus-induced thymidine kinase was synthesized in the infected cells reaching a maximum level at 24 hours post infection (p.i.). In the presence of cytosine arabinoside, thymidine kinase synthesis was enhanced. This suggested that the late (post-replicative) viral function, which turns off thymidine kinase synthesis, was expressed in the infected CEF untreated with the drug. HSV type 1 laboratory strains Kupka and KOS were capable of inducing the synthesis of virus-specific DNA in CEF. But in CEF infected with fresh type 1 virus isolates replication of viral DNA was not observed."}
{"id": "PMID:18915", "title": "Differential expression of D and R components of Epstein-Barr virus early antigen after superinfection and after induction with 5-iododeoxyuridine.", "content": "Three non-productive human lymphoblastoid cell lines, NC-37, RAJI and L-1, either superinfected with Epstein-Barr (EB) virus from P3HR-1 cells or treated with 5-iododexyuridine (IUDR), were studied for the development of early antigen (EA) of EB virus. In all three superinfected cell lines, both the restricted (R) and diffuse (D) componets of EA were synthesized, with R-component formation preceding D-component synthesis. After IUDR treatment both components of EA were only formed in RAJI cells, while in NC37 and L-1 cells only the R-component was synthesized.", "contents": "Differential expression of D and R components of Epstein-Barr virus early antigen after superinfection and after induction with 5-iododeoxyuridine. Three non-productive human lymphoblastoid cell lines, NC-37, RAJI and L-1, either superinfected with Epstein-Barr (EB) virus from P3HR-1 cells or treated with 5-iododexyuridine (IUDR), were studied for the development of early antigen (EA) of EB virus. In all three superinfected cell lines, both the restricted (R) and diffuse (D) componets of EA were synthesized, with R-component formation preceding D-component synthesis. After IUDR treatment both components of EA were only formed in RAJI cells, while in NC37 and L-1 cells only the R-component was synthesized."}
{"id": "PMID:18916", "title": "Production and some properties of neutralizing antigens of herpes simplex virus.", "content": "Human diploid cells (LEP) infected with herpes simplex virus (HSV) type 1 were extracted by treatment with Nonidet P-40. The content of antigens reactive with neutralizing antibody in the clarified extract was measured by the blocking test. Influence of various factors on the production of the blocking antigens (BA) was tested. Highest BA titres in LEP cells were achieved at a multiplicity of infection (m.o.i.) of 0.5 TCD50/cell, medium 199 and 22 to 29 hours incubation at 37 degrees C. The use of resting cultures or the presence of cytosine arabinoside in medium reduced the BA production. The activity of BA was reduced by repeated freezing and thawing. The antigen was stable at -20 and -70 degrees C. One hour heating at 60 degrees C resulted in a marked decrease of the antigen titre. BA was resistant to formalin; formalin treatment did not influence its thermosensitivity.", "contents": "Production and some properties of neutralizing antigens of herpes simplex virus. Human diploid cells (LEP) infected with herpes simplex virus (HSV) type 1 were extracted by treatment with Nonidet P-40. The content of antigens reactive with neutralizing antibody in the clarified extract was measured by the blocking test. Influence of various factors on the production of the blocking antigens (BA) was tested. Highest BA titres in LEP cells were achieved at a multiplicity of infection (m.o.i.) of 0.5 TCD50/cell, medium 199 and 22 to 29 hours incubation at 37 degrees C. The use of resting cultures or the presence of cytosine arabinoside in medium reduced the BA production. The activity of BA was reduced by repeated freezing and thawing. The antigen was stable at -20 and -70 degrees C. One hour heating at 60 degrees C resulted in a marked decrease of the antigen titre. BA was resistant to formalin; formalin treatment did not influence its thermosensitivity."}
{"id": "PMID:18917", "title": "Heterogeneity of pseudorabies virus studied by isoelectric separation.", "content": "Heterogeneity of four lines derived from a single strain of pseudorabies virus (PRV) was studied by isoelectric separation. The individual lines differed in the distribution pattern of infectious fractions separated in the pH range from 3.5 to 10.0. All virus fractions of the virulent and attenuated lines were infectious, but some fractions of the highly attenuated avirulent line were devoid of infectivity. Infectivity of the fractions isolated from the individual PVR lines depended on the degree of attenuation; the higher degree of attenuation, the greater the differences in infectivity of the isolated fractions. The possible causes of the different distribution of infectious fractions obtained by isoelectric separation from virus lines differing in biological properties are discussed. The relationship between physico-chemical and biological properties of PRV is stressed along with the possibilities of applying isoelectric separation in narrow pH gradients.", "contents": "Heterogeneity of pseudorabies virus studied by isoelectric separation. Heterogeneity of four lines derived from a single strain of pseudorabies virus (PRV) was studied by isoelectric separation. The individual lines differed in the distribution pattern of infectious fractions separated in the pH range from 3.5 to 10.0. All virus fractions of the virulent and attenuated lines were infectious, but some fractions of the highly attenuated avirulent line were devoid of infectivity. Infectivity of the fractions isolated from the individual PVR lines depended on the degree of attenuation; the higher degree of attenuation, the greater the differences in infectivity of the isolated fractions. The possible causes of the different distribution of infectious fractions obtained by isoelectric separation from virus lines differing in biological properties are discussed. The relationship between physico-chemical and biological properties of PRV is stressed along with the possibilities of applying isoelectric separation in narrow pH gradients."}
{"id": "PMID:18918", "title": "Nucleic acid biosynthesis in rat embryo cells infected with X14 or H-1 parvovirus.", "content": "Nucleic acid biosynthesis was studied in rat embryo cell (REC) cultures 48 hours after infection with X14 or H-1 parvovirus. The incorporation of 14C-formate and [6-(14C]-orotic acid into purines and pyrimidines of various was lowered after infection with these parvoviruses. 14C-Formate incorporation into acid-soluble thymine was greatly inhibited in H-1 virus-infected cells whereas it was slightly inhibited in X14 virus-infected cells. These results suggest that X14 virus-infected cells can carry out the biosynthesis of thymidylic acid utilizing some endogenous pyrimidine nucleotide (e.g. deoxycytidylic acid, via deoxyuridylic acid). In the infected cells, the nucleoplasmic RNA polymerase activity was strongly inhibited. This results suggests an interference by the two viruses with hosts RNA synthesis.", "contents": "Nucleic acid biosynthesis in rat embryo cells infected with X14 or H-1 parvovirus. Nucleic acid biosynthesis was studied in rat embryo cell (REC) cultures 48 hours after infection with X14 or H-1 parvovirus. The incorporation of 14C-formate and [6-(14C]-orotic acid into purines and pyrimidines of various was lowered after infection with these parvoviruses. 14C-Formate incorporation into acid-soluble thymine was greatly inhibited in H-1 virus-infected cells whereas it was slightly inhibited in X14 virus-infected cells. These results suggest that X14 virus-infected cells can carry out the biosynthesis of thymidylic acid utilizing some endogenous pyrimidine nucleotide (e.g. deoxycytidylic acid, via deoxyuridylic acid). In the infected cells, the nucleoplasmic RNA polymerase activity was strongly inhibited. This results suggests an interference by the two viruses with hosts RNA synthesis."}
{"id": "PMID:18919", "title": "Properties of virions and ribonucleoproteins of Venezuelan equine encephalomyelitis virus.", "content": "The physicochemical properties of Venezuelan equine encephalomyelitis (VEE) virus and of its ribonucleoprotein (RNP) were studied. Upon purification in a discontinuous or linear sucrose gradient, the losses of infectivity were small (25%), and 96% of cellular proteins were removed. The purified virus was homogeneous with respect of sedimentation rate (s20, w = 265 S). The CsCl gradient was unsuitable for purification of infectious virus because the latter was destroyed at high CsCl concentrations. Buoyant density of the virus in CsCl after formaldehyde fixation was 1.21--1.22 g/cm3. Treatment of the virus with 1% Nonidet P-40 proved to be the most effective method for isolation of the RNP. The structures thus obtained contained practically all of the viral RNA and about 20% of viral proteins, and were homogeneous with respect of sedimentation rate (153 S) and buoyant density (1.40--1.42 g/cm3 in CsCl after formaldehyde fixation). The RNPs were sensitive to ribonuclease.", "contents": "Properties of virions and ribonucleoproteins of Venezuelan equine encephalomyelitis virus. The physicochemical properties of Venezuelan equine encephalomyelitis (VEE) virus and of its ribonucleoprotein (RNP) were studied. Upon purification in a discontinuous or linear sucrose gradient, the losses of infectivity were small (25%), and 96% of cellular proteins were removed. The purified virus was homogeneous with respect of sedimentation rate (s20, w = 265 S). The CsCl gradient was unsuitable for purification of infectious virus because the latter was destroyed at high CsCl concentrations. Buoyant density of the virus in CsCl after formaldehyde fixation was 1.21--1.22 g/cm3. Treatment of the virus with 1% Nonidet P-40 proved to be the most effective method for isolation of the RNP. The structures thus obtained contained practically all of the viral RNA and about 20% of viral proteins, and were homogeneous with respect of sedimentation rate (153 S) and buoyant density (1.40--1.42 g/cm3 in CsCl after formaldehyde fixation). The RNPs were sensitive to ribonuclease."}
{"id": "PMID:18920", "title": "Latent infection and measles meningoencephalitis in Syrian hamsters.", "content": "A strain designated 42-Edmonston was isolated from the brain of a Syrian hamster 30 days after inoculation during the neonatal period with the reference \"wild\" measles virus strain Edmonston which produced a latent infection accompanied by production of measles antibody and insignificant pathomorphological changes. Intracerebral inoculation with the 42-Edmonston strain of newborn, one day-and 5-7-day-old Syrian hamsters resulted in the development of acute measles encephalitis with typical clinical symptoms and pathomorphological changes. It is suggested that selection and adaptation of a neurotropic measles virus variant probably had occurred in the course of virus persistence in the Syrian hamster brain.", "contents": "Latent infection and measles meningoencephalitis in Syrian hamsters. A strain designated 42-Edmonston was isolated from the brain of a Syrian hamster 30 days after inoculation during the neonatal period with the reference \"wild\" measles virus strain Edmonston which produced a latent infection accompanied by production of measles antibody and insignificant pathomorphological changes. Intracerebral inoculation with the 42-Edmonston strain of newborn, one day-and 5-7-day-old Syrian hamsters resulted in the development of acute measles encephalitis with typical clinical symptoms and pathomorphological changes. It is suggested that selection and adaptation of a neurotropic measles virus variant probably had occurred in the course of virus persistence in the Syrian hamster brain."}
{"id": "PMID:18921", "title": "Serodiagnosis of influenza by indirect haemagglutination test.", "content": "Results of studies on serodiagnosis of influenza A and B by the indirect haemagglutination test (IHA) with lyophilized erythrocyte diagnostic preparations, highly stable upon storage, are presented. The diagnostic value of the IHA test was in good agreement with, that of virus neutralization tests.", "contents": "Serodiagnosis of influenza by indirect haemagglutination test. Results of studies on serodiagnosis of influenza A and B by the indirect haemagglutination test (IHA) with lyophilized erythrocyte diagnostic preparations, highly stable upon storage, are presented. The diagnostic value of the IHA test was in good agreement with, that of virus neutralization tests."}
{"id": "PMID:18922", "title": "Improved methods of influenza virus propagation. I. Enhancement of virus reproduction in cell cultures.", "content": "Comparative studies on the reproduction of a set of influenza A and B virus strains in different cell cultures were carried out. A cultivation system yielding influenza virus with high infectivity, based on the use of roller cultures of bovine embryo kidney cells, of virus strains adapted to this culture, and of a maintenance medium of improved composition, was developed.", "contents": "Improved methods of influenza virus propagation. I. Enhancement of virus reproduction in cell cultures. Comparative studies on the reproduction of a set of influenza A and B virus strains in different cell cultures were carried out. A cultivation system yielding influenza virus with high infectivity, based on the use of roller cultures of bovine embryo kidney cells, of virus strains adapted to this culture, and of a maintenance medium of improved composition, was developed."}
{"id": "PMID:18923", "title": "Improved methods of influenza virus propagation. II. Characteristics of cell culture and allantoic virus preparations.", "content": "Regular reproduction of influenza A virus with infectious titres of 7.4--8.5 log EID50/0.2 ml was observed in roller bovine embryo kidney cell cultures. The haemagglutinating activity of the cell culture preparations was 8-33-fold lower than that of the allantoic preparations, the infectivity being similar. Cell culture preparations of influenza A/Victoria/35/72 and A /Leningrad/538/74 viruses were markedly immunogenic in laboratory animals and antigenically active in complement fixation (CF) test. The CF activity of liquid and lyophilized preparations remained unchanged for 12--13 months (the period of observation). The stability of infectivity of lyophilized cell culture virus preparations was similar to that of allantoic virus preparations.", "contents": "Improved methods of influenza virus propagation. II. Characteristics of cell culture and allantoic virus preparations. Regular reproduction of influenza A virus with infectious titres of 7.4--8.5 log EID50/0.2 ml was observed in roller bovine embryo kidney cell cultures. The haemagglutinating activity of the cell culture preparations was 8-33-fold lower than that of the allantoic preparations, the infectivity being similar. Cell culture preparations of influenza A/Victoria/35/72 and A /Leningrad/538/74 viruses were markedly immunogenic in laboratory animals and antigenically active in complement fixation (CF) test. The CF activity of liquid and lyophilized preparations remained unchanged for 12--13 months (the period of observation). The stability of infectivity of lyophilized cell culture virus preparations was similar to that of allantoic virus preparations."}
{"id": "PMID:18924", "title": "Analysis of antibody response and immunoglobulins in sera of rabbits and guinea pigs immunized with Coxiella burnetii.", "content": "Rabbit and guinea pig sera and their immunoglobulin fractions (IgM and IgG) were examined by complement-fixation (CF), microagglutination (MA), opsonization-phagocytosis (OP) and serum protection (SP) tests at intervals after immunization with live phase I and phase II Coxiella burnetii suspensions. In general, MA antibodies, but also decreased, earlier than CF antibodies. The anamnestic immune response was higher with lower primary doses. Both phase II and phase I CF and MA antibodies as well as phase I opsonins and protective antibodies were found in either immunoglobulin fraction depending on post-immunization intervals. At later intervals and especially after the second immunizing dose the levels of protective antibodies in whole sera, but mainly in the IgG fractions, showed a better agreement with those of phase I opsonins rather than of phase I CF and MA antibodies.", "contents": "Analysis of antibody response and immunoglobulins in sera of rabbits and guinea pigs immunized with Coxiella burnetii. Rabbit and guinea pig sera and their immunoglobulin fractions (IgM and IgG) were examined by complement-fixation (CF), microagglutination (MA), opsonization-phagocytosis (OP) and serum protection (SP) tests at intervals after immunization with live phase I and phase II Coxiella burnetii suspensions. In general, MA antibodies, but also decreased, earlier than CF antibodies. The anamnestic immune response was higher with lower primary doses. Both phase II and phase I CF and MA antibodies as well as phase I opsonins and protective antibodies were found in either immunoglobulin fraction depending on post-immunization intervals. At later intervals and especially after the second immunizing dose the levels of protective antibodies in whole sera, but mainly in the IgG fractions, showed a better agreement with those of phase I opsonins rather than of phase I CF and MA antibodies."}
{"id": "PMID:18925", "title": "The role of the nucleus in the replication of measles virus.", "content": "The replication of measles and SSPE viruses in enucleate BSC-1 cells was measured by plaque assay, and the synthesis of virus-specific antigen was measured by indirect immunofluorescence. Titres of infectious virus produced in enucleate cells at 24 hours post inoculation (p.i.) were consistently 100-fold less, and the number of enucleate cells containing virus antigen at 30 hours p.i. was 10-fold less, than in nucleate control cultures. Enucleate cells at this time had 30% of the protein synthetic capacity of control nucleate cells, and supported the growth of Semliki Forest virus to titres equivalent to nucleate cell production.", "contents": "The role of the nucleus in the replication of measles virus. The replication of measles and SSPE viruses in enucleate BSC-1 cells was measured by plaque assay, and the synthesis of virus-specific antigen was measured by indirect immunofluorescence. Titres of infectious virus produced in enucleate cells at 24 hours post inoculation (p.i.) were consistently 100-fold less, and the number of enucleate cells containing virus antigen at 30 hours p.i. was 10-fold less, than in nucleate control cultures. Enucleate cells at this time had 30% of the protein synthetic capacity of control nucleate cells, and supported the growth of Semliki Forest virus to titres equivalent to nucleate cell production."}
{"id": "PMID:18926", "title": "Antiviral effect of tebrofen.", "content": "Tebrofen inhibited the replication of western equine encephalomyelitis (WEE) virus in multicycle experiments in chick embryo cell cell cultures. The compound did not inhibit the replication of vaccinia and Newcastle disease viruses.", "contents": "Antiviral effect of tebrofen. Tebrofen inhibited the replication of western equine encephalomyelitis (WEE) virus in multicycle experiments in chick embryo cell cell cultures. The compound did not inhibit the replication of vaccinia and Newcastle disease viruses."}
{"id": "PMID:18927", "title": "Effect of physical and chemical agents on the blue-green algal virus N-1.", "content": "The stability of the blue-green algal virus N-1, infecting the blue-green alga Nostoc muscorum, against temperature, EDTA and pH was studied. Ninety per cent thermal inactivation of virus occured at 55 degrees C in 20 minutes with an average inactivation rate constant of 0.07 per minute; at 60 degrees C the virus was completely inactivated within 5 minutes. 10(-4) M EDTA inactivated 30 per cent of free virus in 60 minutes; 10(-3) M EDTA was completely lethal. Intracellular virus was comparatively resistant to EDTA. The virus was stable in the pH range from 6.7 to 10.5 and was inactivated at acidic pH.", "contents": "Effect of physical and chemical agents on the blue-green algal virus N-1. The stability of the blue-green algal virus N-1, infecting the blue-green alga Nostoc muscorum, against temperature, EDTA and pH was studied. Ninety per cent thermal inactivation of virus occured at 55 degrees C in 20 minutes with an average inactivation rate constant of 0.07 per minute; at 60 degrees C the virus was completely inactivated within 5 minutes. 10(-4) M EDTA inactivated 30 per cent of free virus in 60 minutes; 10(-3) M EDTA was completely lethal. Intracellular virus was comparatively resistant to EDTA. The virus was stable in the pH range from 6.7 to 10.5 and was inactivated at acidic pH."}
{"id": "PMID:18928", "title": "Scanning and transmission electron microscopy of Rickettsia rickettsii propagated in cell culture.", "content": "Scanning electron microscopy utilizing critical-point drying and transmission electron microscopy employing air-dried agar pseudoreplicas and critical-point dried carbon replicas were used to study the surface of Rickettsia rickettsii propagated in cell culture.", "contents": "Scanning and transmission electron microscopy of Rickettsia rickettsii propagated in cell culture. Scanning electron microscopy utilizing critical-point drying and transmission electron microscopy employing air-dried agar pseudoreplicas and critical-point dried carbon replicas were used to study the surface of Rickettsia rickettsii propagated in cell culture."}
{"id": "PMID:18930", "title": "Adrenergic mechanisms in infection. III. alpha-and beta-receptor blocking agents in treatment.", "content": "Raised epinephrine concentrations concentrations developed in the blood of mice near death after an intraperitoneal challenge with 10(9) Staphylococcus aureus or Escherichia coli. Both epinephrine levels were elevated in the urine near death. These challenges were infections and not intoxications, as they could be successfully treated with antibiotics. Using the same model infections, we studied the effect of alpha-and beta-receptor blocking agents and other adrenergically active compounds. The compounds alone were not toxic in the doses used. alpha-Blockers, such as phenoxybenzamine, dibenamine, and ergotamine and beta-blockers, such as butoxamine, timolol, and practolol, were ineffective. Phentolamine alone or propranolol alone showed some evidence of an ability to prolong life in S. aureus infections. Together they lengthened life significantly in S. aureus-challenged mice. In E. coli infections this beneficial effect was not noted. Mice pretreated with reserpine (7 mg/kg) and challenged with S. aureus lived 55% longer than saline-treated controls. Less benefit was noted in E. coli infections. Serontonin treatment was helpful in S. aureus infections and deleterious in E. coli infections.", "contents": "Adrenergic mechanisms in infection. III. alpha-and beta-receptor blocking agents in treatment. Raised epinephrine concentrations concentrations developed in the blood of mice near death after an intraperitoneal challenge with 10(9) Staphylococcus aureus or Escherichia coli. Both epinephrine levels were elevated in the urine near death. These challenges were infections and not intoxications, as they could be successfully treated with antibiotics. Using the same model infections, we studied the effect of alpha-and beta-receptor blocking agents and other adrenergically active compounds. The compounds alone were not toxic in the doses used. alpha-Blockers, such as phenoxybenzamine, dibenamine, and ergotamine and beta-blockers, such as butoxamine, timolol, and practolol, were ineffective. Phentolamine alone or propranolol alone showed some evidence of an ability to prolong life in S. aureus infections. Together they lengthened life significantly in S. aureus-challenged mice. In E. coli infections this beneficial effect was not noted. Mice pretreated with reserpine (7 mg/kg) and challenged with S. aureus lived 55% longer than saline-treated controls. Less benefit was noted in E. coli infections. Serontonin treatment was helpful in S. aureus infections and deleterious in E. coli infections."}
{"id": "PMID:18931", "title": "Effects of pneumococcal infection on rat liver microsomal enzymes and lipogenesis by isolated hepatocytes.", "content": "Modification in the enzymatic complement and lipogenic functions of rat liver endoplasmic reticulum (ER) were shown to occur during pneumococcal sepsis. Glucose-6-phosphatase, 5'nucleotidase, esterase, and NADPH cytochrome C reductase decreased in activity by as much as 50% with respect to controls. Hydroxymethylglutaryl-CoA and NADH cytochrome C reductases were increased 6-and 2-fold, respectively. Alkaline phosphatase and inosine-5'-diphosphatase did not differ with respect to fasted controls. The lipogenic capacity of the ER was shown to be enhanced. In vitro [14C]acetate incorporation into cholesterol and other lipids by hepatocytes isolated from infected rats was increased 2-to 10-fold. It is concluded that the flow of acetyl-CoA in liver cell of Streptococcus pneumoniae-infected rats is toward lipogenesis rather than ketogenesis.", "contents": "Effects of pneumococcal infection on rat liver microsomal enzymes and lipogenesis by isolated hepatocytes. Modification in the enzymatic complement and lipogenic functions of rat liver endoplasmic reticulum (ER) were shown to occur during pneumococcal sepsis. Glucose-6-phosphatase, 5'nucleotidase, esterase, and NADPH cytochrome C reductase decreased in activity by as much as 50% with respect to controls. Hydroxymethylglutaryl-CoA and NADH cytochrome C reductases were increased 6-and 2-fold, respectively. Alkaline phosphatase and inosine-5'-diphosphatase did not differ with respect to fasted controls. The lipogenic capacity of the ER was shown to be enhanced. In vitro [14C]acetate incorporation into cholesterol and other lipids by hepatocytes isolated from infected rats was increased 2-to 10-fold. It is concluded that the flow of acetyl-CoA in liver cell of Streptococcus pneumoniae-infected rats is toward lipogenesis rather than ketogenesis."}
{"id": "PMID:18932", "title": "Prostaglandin E2-hemoglobin AA and SS erythrocyte interaction (prostaglandin-erythrocyte interaction).", "content": "Prostaglandin E2 (PGE2), at concentration larger than or equal to 5 x 10(4) ng/ml, induced discocyte leads to echinocyte transformation of saline-suspended hemoglobin (Hb) AA and SS erythrocytes. This erythrocyte transformation is concentration-dependent and is reversible at room temperature after 90-120 min. The Hb SS erythrocytes treated with PGE2 did not exhibit accelerated sickling or increased formation of sickled echinocytes. Erythrocytes suspended in autologous plasma treated with PGE2, 2 X 10(6) ng/ml, did not exhibit echinocytic transformation probably because of drug binding to the plasma proteins. Other in vitro studies showed that PGE2 of concentrations of 10-500 ng/ml had no adverse effects on intact, plasma-suspended Hb SS erythrocytes. These Hb SS erythrocytes were examined for changes in morphology, potassium and calcium flux, and blood viscosity under oxygenated and hypoxic conditions.", "contents": "Prostaglandin E2-hemoglobin AA and SS erythrocyte interaction (prostaglandin-erythrocyte interaction). Prostaglandin E2 (PGE2), at concentration larger than or equal to 5 x 10(4) ng/ml, induced discocyte leads to echinocyte transformation of saline-suspended hemoglobin (Hb) AA and SS erythrocytes. This erythrocyte transformation is concentration-dependent and is reversible at room temperature after 90-120 min. The Hb SS erythrocytes treated with PGE2 did not exhibit accelerated sickling or increased formation of sickled echinocytes. Erythrocytes suspended in autologous plasma treated with PGE2, 2 X 10(6) ng/ml, did not exhibit echinocytic transformation probably because of drug binding to the plasma proteins. Other in vitro studies showed that PGE2 of concentrations of 10-500 ng/ml had no adverse effects on intact, plasma-suspended Hb SS erythrocytes. These Hb SS erythrocytes were examined for changes in morphology, potassium and calcium flux, and blood viscosity under oxygenated and hypoxic conditions."}
{"id": "PMID:18933", "title": "Biological activity of dilute isoproterenol solution stored for long periods in plastic bags.", "content": "The effect of long-term storage in polyvinyl chloride bags on the biological activity and the chemical stability of isoproterenol was studied. A freshly prepared solution of isoproterenol, isoproterenol solution stored for six months and isoproterenol stored for 30 months were infused into the coronary circulation of 14 isolated rabbit hearts; heart rates were determined. Spectrophotometric studies to determine stability at various pH levels were also done. Aging of the solutions at pH 4 and at a concentration of 4 microgram/ml caused no significant impairment of their potency. Solutions above pH 6 were unstable.", "contents": "Biological activity of dilute isoproterenol solution stored for long periods in plastic bags. The effect of long-term storage in polyvinyl chloride bags on the biological activity and the chemical stability of isoproterenol was studied. A freshly prepared solution of isoproterenol, isoproterenol solution stored for six months and isoproterenol stored for 30 months were infused into the coronary circulation of 14 isolated rabbit hearts; heart rates were determined. Spectrophotometric studies to determine stability at various pH levels were also done. Aging of the solutions at pH 4 and at a concentration of 4 microgram/ml caused no significant impairment of their potency. Solutions above pH 6 were unstable."}
{"id": "PMID:18936", "title": "Continuous subcutaneous pH measurement in human fetuses: correlations with scalp and umbilical blood pH.", "content": "The subcutaneous pH values of 42 fetuses has been measured continuously during labor with the use of the electrode designed by Stamm and associates. We have obtained 60 per cent good tracings. The results have confirmed the reliability of the subcutaneous pH measurement, if the electrode is correctly inserted, when compared with both capillary and umbilical artery blood pH measurements (r = 0.91, p less than 0.001 and 0.83, p less than 0.001, respectively). Technical improvements appear to be necessary prior to widespread clinical use of continuous pH measurement.", "contents": "Continuous subcutaneous pH measurement in human fetuses: correlations with scalp and umbilical blood pH. The subcutaneous pH values of 42 fetuses has been measured continuously during labor with the use of the electrode designed by Stamm and associates. We have obtained 60 per cent good tracings. The results have confirmed the reliability of the subcutaneous pH measurement, if the electrode is correctly inserted, when compared with both capillary and umbilical artery blood pH measurements (r = 0.91, p less than 0.001 and 0.83, p less than 0.001, respectively). Technical improvements appear to be necessary prior to widespread clinical use of continuous pH measurement."}
{"id": "PMID:18937", "title": "Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis.", "content": "Hyperplastic liver lesions which develop following administration of hepatocarcinogens have been implicated as probable precursors for the cancers which ultimately develop. Some, and possibly all, of these putative precursor lesions are resistant to the necrogenic and growth-inhibitory action of hepatocarcinogens and other hepatotoxins. An in vivo assay system based on this resistance phenomenon has been developed which encourages the rapid selective growth of carcinogen-altered hepatocytes, facilitating their early identification. The system consists of a) single carcinogenic dose of diethylnitrosamine (DEN), b) short-term dietary exposure to 2-acetylaminofluorene (2-AAF) sufficient to suppress growth of virtually all normal hepatocytes, and c) partial hepatectomy (PH) to actuate rapid growth of DEN-altered hepatocytes not suppressed by 2-AAF. Following PH, the DEN-altered hepatocytes grow out as basophilic foci which are distributed randomly throughout the 2-AAF-suppressed parenchyma. Within 1 week they can be seen as tiny, discrete, translucent nodules on the capsular and cut surface of the remaining lobes. The lesions continue to proliferate and become histologically indistinguishable from typical carcinogen-induced hyperplastic liver nodules frequently described in the literature. These in turn appear to be precursor lesions for at least some hepatocellular carcinomas. Future experimentation based on this phenomenon of \"selective resistance to cytotoxicity\" should prove valuable in answering specific questions about the carcinogenic process in liver and possibly in other tissues.", "contents": "Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. Hyperplastic liver lesions which develop following administration of hepatocarcinogens have been implicated as probable precursors for the cancers which ultimately develop. Some, and possibly all, of these putative precursor lesions are resistant to the necrogenic and growth-inhibitory action of hepatocarcinogens and other hepatotoxins. An in vivo assay system based on this resistance phenomenon has been developed which encourages the rapid selective growth of carcinogen-altered hepatocytes, facilitating their early identification. The system consists of a) single carcinogenic dose of diethylnitrosamine (DEN), b) short-term dietary exposure to 2-acetylaminofluorene (2-AAF) sufficient to suppress growth of virtually all normal hepatocytes, and c) partial hepatectomy (PH) to actuate rapid growth of DEN-altered hepatocytes not suppressed by 2-AAF. Following PH, the DEN-altered hepatocytes grow out as basophilic foci which are distributed randomly throughout the 2-AAF-suppressed parenchyma. Within 1 week they can be seen as tiny, discrete, translucent nodules on the capsular and cut surface of the remaining lobes. The lesions continue to proliferate and become histologically indistinguishable from typical carcinogen-induced hyperplastic liver nodules frequently described in the literature. These in turn appear to be precursor lesions for at least some hepatocellular carcinomas. Future experimentation based on this phenomenon of \"selective resistance to cytotoxicity\" should prove valuable in answering specific questions about the carcinogenic process in liver and possibly in other tissues."}
{"id": "PMID:18938", "title": "Vitamin K2 colonic and ileal in vivo absorption: bile, fatty acids, and pH effects on transport.", "content": "Colonic and ileal absorption of vitamin K2 ([2-methyl-3H]menaquinone-9) was investigated in the conscious rat. When the absorption rate was plotted against the perfusate concentration, a linear relationship was found between these two parameters in the ileum and colon. The absorption rate of menaquinone by the ileum was increased as the bile salt concentration, degree of unsaturation of the added long-chain fatty acids, hydrogen ion concentration, and perfusate flow rates were increased. Colonic menaquinone absorption decreased as the bile salt concentration was increased. Menaquinone colonic absoprtion increased as the pH decreased, but no change was noted as the perfusion rate was increased. The present experimental observations in vivo, coupled with prior observations in vitro, indicate that absorption of menaquinone by the ileum and colon occurs by a passive diffusion process that is modified by variations in the perfusate bile salt concentration, the presence of unsaturated fatty acids, and the perfusate pH. The present observations indicate that the mammalian colon and terminal ileum can provide a constant source of vitamin K to aid hemostasis despite episodic lack of dietary vitamin K.", "contents": "Vitamin K2 colonic and ileal in vivo absorption: bile, fatty acids, and pH effects on transport. Colonic and ileal absorption of vitamin K2 ([2-methyl-3H]menaquinone-9) was investigated in the conscious rat. When the absorption rate was plotted against the perfusate concentration, a linear relationship was found between these two parameters in the ileum and colon. The absorption rate of menaquinone by the ileum was increased as the bile salt concentration, degree of unsaturation of the added long-chain fatty acids, hydrogen ion concentration, and perfusate flow rates were increased. Colonic menaquinone absorption decreased as the bile salt concentration was increased. Menaquinone colonic absoprtion increased as the pH decreased, but no change was noted as the perfusion rate was increased. The present experimental observations in vivo, coupled with prior observations in vitro, indicate that absorption of menaquinone by the ileum and colon occurs by a passive diffusion process that is modified by variations in the perfusate bile salt concentration, the presence of unsaturated fatty acids, and the perfusate pH. The present observations indicate that the mammalian colon and terminal ileum can provide a constant source of vitamin K to aid hemostasis despite episodic lack of dietary vitamin K."}
{"id": "PMID:18939", "title": "Glucose utilization and role of blood in endotoxin shock.", "content": "The present study was conducted to explore influences modifying glucose uptake in canine blood administered LD100 E. coli endotoxin. Particular emphasis was given to assay the role of the white blood cell (WBC) in glucose utilization. Significant increases in glucose uptake and lactic acid production, attributed to increased activity of the WBC, were observed 1-3 h after endotoxin was added to blood in vitro. Although a net increase in glucose utilization was noted, endotoxin simultaneously exerted adverse effects by depressing glucose uptake below predicted values (Q10 = 2.12 with LD100 endotoxin vs. 2.78 in saline controls) and increasing WBC mortality rate. Blood from dogs pretreated with sublethal doses of endotoxin in vivo utilized glucose at an accelerated rate when subjected to endotoxin in vitro. Excess glucose was consumed because of elevated numbers of white blood cells although additional glucose requirements after endotoxin were independent of temperature between the ranges of 34-41 degrees C. All animals pretreated with daily sublethal injections of endotoxin  for 3 days survived superlethal doses of endotoxin.", "contents": "Glucose utilization and role of blood in endotoxin shock. The present study was conducted to explore influences modifying glucose uptake in canine blood administered LD100 E. coli endotoxin. Particular emphasis was given to assay the role of the white blood cell (WBC) in glucose utilization. Significant increases in glucose uptake and lactic acid production, attributed to increased activity of the WBC, were observed 1-3 h after endotoxin was added to blood in vitro. Although a net increase in glucose utilization was noted, endotoxin simultaneously exerted adverse effects by depressing glucose uptake below predicted values (Q10 = 2.12 with LD100 endotoxin vs. 2.78 in saline controls) and increasing WBC mortality rate. Blood from dogs pretreated with sublethal doses of endotoxin in vivo utilized glucose at an accelerated rate when subjected to endotoxin in vitro. Excess glucose was consumed because of elevated numbers of white blood cells although additional glucose requirements after endotoxin were independent of temperature between the ranges of 34-41 degrees C. All animals pretreated with daily sublethal injections of endotoxin  for 3 days survived superlethal doses of endotoxin."}
{"id": "PMID:18941", "title": "Role of sympathetics in the response to acute venous occlusion.", "content": "The effect of venous ligation and subsequent blockade of alpha receptors on hindlimb venous pressure, vascular resistance, oxygen extraction and carbon dioxide removal was evaluated in mongrel dogs with use of constant-flow perfusion of the extremity bed. Perfusion, metatarsal vein, femoral vein, and central vein pressures, and changes in paw and thigh circumference were recorded in mongrel dogs in which the hindlimb was perfused at a constant flow. Arterial, metatarsal venous, and femoral venous blood gases were drawn and analyzed for arteriovenous oxygen and carbon dioxide differences. Measurements were repeated following extensive ligation of veins and after subsequent alpha-receptor blockade with Dibenzyline. Findings indicated that ligation of extremity veins resulted in an active increase in total limb resistance upstream from the ligation, and an increase in volume of the limb. Following alpha-adrenergic blockade with Dibenzyline, limb volume increased and oxygen extraction decreased below control levels. The reflex constriction following ligation of veins protected against the detrimental effect of excessive accumulation of fluid in tissue spaces.", "contents": "Role of sympathetics in the response to acute venous occlusion. The effect of venous ligation and subsequent blockade of alpha receptors on hindlimb venous pressure, vascular resistance, oxygen extraction and carbon dioxide removal was evaluated in mongrel dogs with use of constant-flow perfusion of the extremity bed. Perfusion, metatarsal vein, femoral vein, and central vein pressures, and changes in paw and thigh circumference were recorded in mongrel dogs in which the hindlimb was perfused at a constant flow. Arterial, metatarsal venous, and femoral venous blood gases were drawn and analyzed for arteriovenous oxygen and carbon dioxide differences. Measurements were repeated following extensive ligation of veins and after subsequent alpha-receptor blockade with Dibenzyline. Findings indicated that ligation of extremity veins resulted in an active increase in total limb resistance upstream from the ligation, and an increase in volume of the limb. Following alpha-adrenergic blockade with Dibenzyline, limb volume increased and oxygen extraction decreased below control levels. The reflex constriction following ligation of veins protected against the detrimental effect of excessive accumulation of fluid in tissue spaces."}
{"id": "PMID:18942", "title": "The effects of purified cathepsin D infusions in intact animals.", "content": "Cathepsin D, a potent acid proteinase, has been implicated in the pathogenesis of circulatory shock. The infusion of purified preparations of cathepsin D into intact animals resulted in significant depressions in core body temperature but failed to reproduce the cardiovascular disturbances seen in shock states.", "contents": "The effects of purified cathepsin D infusions in intact animals. Cathepsin D, a potent acid proteinase, has been implicated in the pathogenesis of circulatory shock. The infusion of purified preparations of cathepsin D into intact animals resulted in significant depressions in core body temperature but failed to reproduce the cardiovascular disturbances seen in shock states."}
{"id": "PMID:18953", "title": "Acid-base status in diabetic mothers and their infants following general or spinal anesthesia for cesarean section.", "content": "Acid-base status was studied in 30 diabetic mothers and their infants and in 30 healthy mothers and their babies after general or spinal anesthesia for cesarean section. A normal acid-base state was found for the diabetic subjects following general or spinal anesthesia. However, the infants of diabetic mothers given spinal anesthesia had an average pH of 7.20 and a base excess value of -5.67 mEq/l in umbilical-artery blood at delivery. These values were significantly lower than those observed in the infants of the other groups, where the average pH was between 7.28 and 7.30 and the base excess between -1.87 mEq/l and 1.00 mEq/l. These findings were significantly related to maternal diabetes and maternal hypotension.", "contents": "Acid-base status in diabetic mothers and their infants following general or spinal anesthesia for cesarean section. Acid-base status was studied in 30 diabetic mothers and their infants and in 30 healthy mothers and their babies after general or spinal anesthesia for cesarean section. A normal acid-base state was found for the diabetic subjects following general or spinal anesthesia. However, the infants of diabetic mothers given spinal anesthesia had an average pH of 7.20 and a base excess value of -5.67 mEq/l in umbilical-artery blood at delivery. These values were significantly lower than those observed in the infants of the other groups, where the average pH was between 7.28 and 7.30 and the base excess between -1.87 mEq/l and 1.00 mEq/l. These findings were significantly related to maternal diabetes and maternal hypotension."}
{"id": "PMID:18957", "title": "Double-blind trial of oral carbuterol in bronchial asthma.", "content": "A double-blind comparison of 2 and 3 mg oral doses of carbuterol, a beta sympathomimetic drug with preferential selectivity for bronchial smooth muscle, was made with 25 and 35 mg doses of ephedrine sulfate over a six-month period in 26 patients with bronchial asthma. Spirometry was done before and three hours after administration of 3 mg of carbuterol or 35 mg of ephedrine sulfate at intervals of two weeks and one, four and six months. The data suggest a cumulative improvement in pulmonary function status with continued oral carbuterol use over the six-month period. However, the clinical effectiveness of the drug on pulmonary function was not clearly distinguishable from that of ephedrine in the present study.", "contents": "Double-blind trial of oral carbuterol in bronchial asthma. A double-blind comparison of 2 and 3 mg oral doses of carbuterol, a beta sympathomimetic drug with preferential selectivity for bronchial smooth muscle, was made with 25 and 35 mg doses of ephedrine sulfate over a six-month period in 26 patients with bronchial asthma. Spirometry was done before and three hours after administration of 3 mg of carbuterol or 35 mg of ephedrine sulfate at intervals of two weeks and one, four and six months. The data suggest a cumulative improvement in pulmonary function status with continued oral carbuterol use over the six-month period. However, the clinical effectiveness of the drug on pulmonary function was not clearly distinguishable from that of ephedrine in the present study."}
{"id": "PMID:18958", "title": "Newer medications to aid treatment of asthma.", "content": "The selective beta-2 adrenergic bronchodilator preparations should be considered the medications for the first line of defense in the treatment of the average asthmatic patient. Theophylline and derivatives of theophylline are the second line of defense. Cromolyn sodium, atropine and derivatives, corticosteroids and other selected agents follow, depending on the individual case and the circumstances involved.", "contents": "Newer medications to aid treatment of asthma. The selective beta-2 adrenergic bronchodilator preparations should be considered the medications for the first line of defense in the treatment of the average asthmatic patient. Theophylline and derivatives of theophylline are the second line of defense. Cromolyn sodium, atropine and derivatives, corticosteroids and other selected agents follow, depending on the individual case and the circumstances involved."}
{"id": "PMID:18961", "title": "[Toxico-pharmacological study of lyophilized sodium nitroprusside (SNP)].", "content": "Sodium nitroprusside (SNP) shows a strong hypotensive activity not only in normotensive animals but also in the presence of experimentally induced arterial hypertension. Its use in intravenous perfusion produces the rapid induction of arterial hypotension lasting or only slightly exceeding the time of its administration. Most investigators consider this hypotensive activity related to the fall in peripheral resistance, as is supported by the considerable fall in diastolic blood pressure. However, an effect of SNP on heart function cannot be ruled out. After four weeks' treatment at dosages corresponding to one tenth of the LD 50, no local or general toxicity could be demonstrated.", "contents": "[Toxico-pharmacological study of lyophilized sodium nitroprusside (SNP)]. Sodium nitroprusside (SNP) shows a strong hypotensive activity not only in normotensive animals but also in the presence of experimentally induced arterial hypertension. Its use in intravenous perfusion produces the rapid induction of arterial hypotension lasting or only slightly exceeding the time of its administration. Most investigators consider this hypotensive activity related to the fall in peripheral resistance, as is supported by the considerable fall in diastolic blood pressure. However, an effect of SNP on heart function cannot be ruled out. After four weeks' treatment at dosages corresponding to one tenth of the LD 50, no local or general toxicity could be demonstrated."}
{"id": "PMID:18964", "title": "[Use of sodium nitroprusside in cardiology].", "content": "Sodium nitroprusside (SNP) is rarely used in cardiology. It is reserved traditionally for severe episodes of arterial hypertension. Certain states of refractory heart failure represent new indications for use, which implies a double haemodynamic monitoring system: continuous control of systemic blood pressure by intra-arterial catheterization; control of pulmonary pressure and repeated measurements of cardiac output. Prolonged treatment requires continuous biological monitoring of toxicity and careful control of kidney function. As a moderator of blood pressure, SNP is remarkably effective. The hypotensive effect is immediate, readily reversible and generally tachyphylaxis is not observed. The effect of SNP on cardiac work is one of double load reduction: mainly a reduction in afterload or pressure and systemic resistance and a reduction in preload or pressure of ventricular filling. In this respect, SNP can be used effectively for severe cases of heart failure intractable to traditional cardio-stimulatory and diuretic treatments and stemming from diverse causes: acute stage of myocardial infarction, ventricular dilatation, mitral papillary syndrome, heart failure, either subacute or chronic, of various causes. As a rule, the immediate results are positive. Taking the patient off the drug can be difficult and may cause a return to the previous haemodynamic situation.", "contents": "[Use of sodium nitroprusside in cardiology]. Sodium nitroprusside (SNP) is rarely used in cardiology. It is reserved traditionally for severe episodes of arterial hypertension. Certain states of refractory heart failure represent new indications for use, which implies a double haemodynamic monitoring system: continuous control of systemic blood pressure by intra-arterial catheterization; control of pulmonary pressure and repeated measurements of cardiac output. Prolonged treatment requires continuous biological monitoring of toxicity and careful control of kidney function. As a moderator of blood pressure, SNP is remarkably effective. The hypotensive effect is immediate, readily reversible and generally tachyphylaxis is not observed. The effect of SNP on cardiac work is one of double load reduction: mainly a reduction in afterload or pressure and systemic resistance and a reduction in preload or pressure of ventricular filling. In this respect, SNP can be used effectively for severe cases of heart failure intractable to traditional cardio-stimulatory and diuretic treatments and stemming from diverse causes: acute stage of myocardial infarction, ventricular dilatation, mitral papillary syndrome, heart failure, either subacute or chronic, of various causes. As a rule, the immediate results are positive. Taking the patient off the drug can be difficult and may cause a return to the previous haemodynamic situation."}
{"id": "PMID:18967", "title": "[Changes in serum and urinary magnesium during and after extracorporeal circulation in cardiac surgery in children].", "content": "Magnesium plays an essential role in the processes of myocardial contraction and conduction. In cardiovascular surgery, extracorporeal circulation (ECC) in haemodilution results in various electrolyte distrubances, with invariably hypomagnesaemia. A group of 13 children undergoing open heart surgery was compared with a group of 17 children operated upon under the same conditions but with the addition of magnesium to the filling solution for the extracorporeal circulation. Changes in blood and urinary electrolytes during and after ECC were studied. Hypomagnesaemia was seen in both groups after surgery but the provision of magnesium supplements shortened the duration. In addition, blood phosphate levels remained significantly higher in the group receiving magnesium. The significance of these various findings is discussed and a technique for the provision of magnesium supplements is proposed.", "contents": "[Changes in serum and urinary magnesium during and after extracorporeal circulation in cardiac surgery in children]. Magnesium plays an essential role in the processes of myocardial contraction and conduction. In cardiovascular surgery, extracorporeal circulation (ECC) in haemodilution results in various electrolyte distrubances, with invariably hypomagnesaemia. A group of 13 children undergoing open heart surgery was compared with a group of 17 children operated upon under the same conditions but with the addition of magnesium to the filling solution for the extracorporeal circulation. Changes in blood and urinary electrolytes during and after ECC were studied. Hypomagnesaemia was seen in both groups after surgery but the provision of magnesium supplements shortened the duration. In addition, blood phosphate levels remained significantly higher in the group receiving magnesium. The significance of these various findings is discussed and a technique for the provision of magnesium supplements is proposed."}
{"id": "PMID:18968", "title": "[Action of Triv\u00e9 1000 on hemostasis and hematocrit].", "content": "The action of lipids on haemostasis has already been shown. The authors study possible changes of haemostasis induced by the use of a substance: Trive 1000 containing 3.8 g of Soya oil and 0.3 g of Soya lecithin per 100 ml. Twenty patient received 1 litre per day over a period of ten days and were compared with 16 controls receiving glucose and amino acides without lipids. Studies of haemostasis included: overall coagulation by the thrombo-elastogram, P.R.P. (platelet rich plasma), estimation of the co-factors of the prothrombin complex, thrombin and reptilase times, platelet count, platelet stickiness using the method of HELLEM, platelet aggregation using the method of Born, plasminogen and plasmin activity by the pH STAT method, and P.D.F. levels. These examinations were carried out on the 1st, 3rd, 5th, 7th and 9th postoperative days. The results in the patients receiving Trive 1000 were as follows: no change in blood coagulation, progressive fall in platelet activity in the sense of hypoaggregability which was significant from the 5th day onwards only. There was no change in fibrinolysis. By contrast, there was anaemia, as determined on the basis of a fall in haematocrit, maximal on the 5th day and attributed by the authors to the haemolytic properties of triglycerides. In conclusion, Trive 1000 had no signifcant influence on haemostasis, apart from platelet hypoaggregability of moderate degree after prolonged treatment and perhaps haemolytic anaemia.", "contents": "[Action of Triv\u00e9 1000 on hemostasis and hematocrit]. The action of lipids on haemostasis has already been shown. The authors study possible changes of haemostasis induced by the use of a substance: Trive 1000 containing 3.8 g of Soya oil and 0.3 g of Soya lecithin per 100 ml. Twenty patient received 1 litre per day over a period of ten days and were compared with 16 controls receiving glucose and amino acides without lipids. Studies of haemostasis included: overall coagulation by the thrombo-elastogram, P.R.P. (platelet rich plasma), estimation of the co-factors of the prothrombin complex, thrombin and reptilase times, platelet count, platelet stickiness using the method of HELLEM, platelet aggregation using the method of Born, plasminogen and plasmin activity by the pH STAT method, and P.D.F. levels. These examinations were carried out on the 1st, 3rd, 5th, 7th and 9th postoperative days. The results in the patients receiving Trive 1000 were as follows: no change in blood coagulation, progressive fall in platelet activity in the sense of hypoaggregability which was significant from the 5th day onwards only. There was no change in fibrinolysis. By contrast, there was anaemia, as determined on the basis of a fall in haematocrit, maximal on the 5th day and attributed by the authors to the haemolytic properties of triglycerides. In conclusion, Trive 1000 had no signifcant influence on haemostasis, apart from platelet hypoaggregability of moderate degree after prolonged treatment and perhaps haemolytic anaemia."}
{"id": "PMID:18969", "title": "[Study of tracheal pressures transmitted by intubation tube balloons].", "content": "In the light of experimental studies on balloons of several intubation tubes, the concepts of occlusive pressure, tracheal pressure and minimum occlusive volume are defined and dissociated. An in vivo study made it possible to determine the importance of the tracheal mucous pulse, the suppression of which could contribute to tracheal stenosis.", "contents": "[Study of tracheal pressures transmitted by intubation tube balloons]. In the light of experimental studies on balloons of several intubation tubes, the concepts of occlusive pressure, tracheal pressure and minimum occlusive volume are defined and dissociated. An in vivo study made it possible to determine the importance of the tracheal mucous pulse, the suppression of which could contribute to tracheal stenosis."}
{"id": "PMID:18970", "title": "[A case of gastric rupture caused by oxygen therapy by the nasal route].", "content": "The introduction of a catheter for oxygen therapy by the pernasal route, pushed almost into the esophagus led to a gastric rupture. Discussion of this case and of 8 cases already published in the literature.", "contents": "[A case of gastric rupture caused by oxygen therapy by the nasal route]. The introduction of a catheter for oxygen therapy by the pernasal route, pushed almost into the esophagus led to a gastric rupture. Discussion of this case and of 8 cases already published in the literature."}
{"id": "PMID:18971", "title": "[Study of a new anesthetic agent: etomidate (R 26490). Electroencephalographic aspects].", "content": "Etomidate or R 26490 is a new hypnotic agent produced by JANSSEN and al. in 1971. The first human experimentation was performed in 1972. The authors used Etomidate for 300 anaesthetics given for neuroradiological investigations. Two protocols were used for study: 25 anaesthetics were given with Etomidate as sole anaesthetic to outline its specific properties; 275 angiographies were performed with a combination of Etomidate and fentanyl. In protocol no. 1, the mean consumption was for 1,85 mg/kg/h, in protocol no. 2, the mean consumption was of 0,9 mg/kg/h. Pharmacological study of this drug defines it as a short acting hypnotic agent of low toxicity. Clinical observation shows cardiovascular and respiratory stability. However, frequent myoclonias were noted, when Etomidate was given as a sole anaesthetic. EEG recording and evoked response encephalography helped to outline some effects of Etomidate on central nervous system.", "contents": "[Study of a new anesthetic agent: etomidate (R 26490). Electroencephalographic aspects]. Etomidate or R 26490 is a new hypnotic agent produced by JANSSEN and al. in 1971. The first human experimentation was performed in 1972. The authors used Etomidate for 300 anaesthetics given for neuroradiological investigations. Two protocols were used for study: 25 anaesthetics were given with Etomidate as sole anaesthetic to outline its specific properties; 275 angiographies were performed with a combination of Etomidate and fentanyl. In protocol no. 1, the mean consumption was for 1,85 mg/kg/h, in protocol no. 2, the mean consumption was of 0,9 mg/kg/h. Pharmacological study of this drug defines it as a short acting hypnotic agent of low toxicity. Clinical observation shows cardiovascular and respiratory stability. However, frequent myoclonias were noted, when Etomidate was given as a sole anaesthetic. EEG recording and evoked response encephalography helped to outline some effects of Etomidate on central nervous system."}
{"id": "PMID:18972", "title": "Replication of swine and equine influenza viruses in canine kidney cells.", "content": "Both swine and equine influenza viruses were replicated in Madin-Darby canine kidney cells. Hemagglutinin and complement-fixing antigens were synthesized at 4 to 8 hours postinfection and reached maximal synthesis at 16 to 20 hours. Neuraminidase activity increased 9- to 11-fold; 50% of the total hemagglutinin antigen was made before the infective virus progeny was detected.", "contents": "Replication of swine and equine influenza viruses in canine kidney cells. Both swine and equine influenza viruses were replicated in Madin-Darby canine kidney cells. Hemagglutinin and complement-fixing antigens were synthesized at 4 to 8 hours postinfection and reached maximal synthesis at 16 to 20 hours. Neuraminidase activity increased 9- to 11-fold; 50% of the total hemagglutinin antigen was made before the infective virus progeny was detected."}
{"id": "PMID:18979", "title": "[Relationship between the quality of the inoculum material and carminomycin biosynthesis by a culture of Actinomadura carminata].", "content": "The effect of the inoculum mycelium quality on carminomycin biosynthesis by Actinomadura carminata was studied. The time of the organism growth on the culture medium containing cornsteep liquor continued for 6 hours without losing by the inoculum of its seeding qualities during that period. The mycelium growth in the inoculum was more intensive under conditions of moderate aeration, i.e. 0.98-2.64 mg O2H1-min. Anincrease in the aeration rate up to 18.56 mg O2/1-min resulted in the growth suppression up to 40 per cent. No correlation between the aeration rate during the inoculum growth and the culture capacity for carminomycin biosynthesis and of the content of the complex in active components the fermentation medium were observed, when a 5-10 per cent of inoculum was used.", "contents": "[Relationship between the quality of the inoculum material and carminomycin biosynthesis by a culture of Actinomadura carminata]. The effect of the inoculum mycelium quality on carminomycin biosynthesis by Actinomadura carminata was studied. The time of the organism growth on the culture medium containing cornsteep liquor continued for 6 hours without losing by the inoculum of its seeding qualities during that period. The mycelium growth in the inoculum was more intensive under conditions of moderate aeration, i.e. 0.98-2.64 mg O2H1-min. Anincrease in the aeration rate up to 18.56 mg O2/1-min resulted in the growth suppression up to 40 per cent. No correlation between the aeration rate during the inoculum growth and the culture capacity for carminomycin biosynthesis and of the content of the complex in active components the fermentation medium were observed, when a 5-10 per cent of inoculum was used."}
{"id": "PMID:18980", "title": "[Physicochmemical characteristics of the new antineoplastic antibiotic, nocamycin].", "content": "Nocamycin is produced by Nocardiopsis syringae. It is recovered from the culture fluid by extraction with chloroform. The molecular weight of the crystalline antibiotic is 503, its melting point is 147--149 degrees, [alpha]20 degrees D = --50 degrees (c. 0.21, chloroform), lambdamax235 and 348 nm(E1%sm= = 150 and 420), the summation formula is C26 H33NO9, the biological activity is 100000 Units/mg with respect to Bacillus mycoides. Nocamycin forms salts with alkalies soluble in water. On hydrolysis with an alkali it forms carbonic acid having no ester bond (IP spectrum) and methoxylic group present in the antibiotic molecule. Nocamycin is a new natural substance.", "contents": "[Physicochmemical characteristics of the new antineoplastic antibiotic, nocamycin]. Nocamycin is produced by Nocardiopsis syringae. It is recovered from the culture fluid by extraction with chloroform. The molecular weight of the crystalline antibiotic is 503, its melting point is 147--149 degrees, [alpha]20 degrees D = --50 degrees (c. 0.21, chloroform), lambdamax235 and 348 nm(E1%sm= = 150 and 420), the summation formula is C26 H33NO9, the biological activity is 100000 Units/mg with respect to Bacillus mycoides. Nocamycin forms salts with alkalies soluble in water. On hydrolysis with an alkali it forms carbonic acid having no ester bond (IP spectrum) and methoxylic group present in the antibiotic molecule. Nocamycin is a new natural substance."}
{"id": "PMID:18981", "title": "[Effect of different forms of nitrogen in the biosynthesis of gentamicin by a Micromonospora purpurea var. violacea 1935 culture].", "content": "The effect of different inorganic sources of reduced and oxidized nitrogen on biosynthesis of gentamicin was studied. It was shown that both the ammonium and the nitrate nitrogen were consumed by the antibiotic-producing organism. Out of all the salts tested only ammonium sulfate stimulated the biosynthesis of gentamicin. The positive role of this salt was due to both the ammonium and the sulfogroup, since the presence of the sulfogroup alone in sodium sulfat, magnesium or sulfuric acid resulted only in partial stimulation of gentamicin biosynthesis. Simultaneous addition of sulfuric acid ammonium nitrate which suppressed the antibiotic biosynthesis when used alone was equal to introduction of ammonium sulfate.", "contents": "[Effect of different forms of nitrogen in the biosynthesis of gentamicin by a Micromonospora purpurea var. violacea 1935 culture]. The effect of different inorganic sources of reduced and oxidized nitrogen on biosynthesis of gentamicin was studied. It was shown that both the ammonium and the nitrate nitrogen were consumed by the antibiotic-producing organism. Out of all the salts tested only ammonium sulfate stimulated the biosynthesis of gentamicin. The positive role of this salt was due to both the ammonium and the sulfogroup, since the presence of the sulfogroup alone in sodium sulfat, magnesium or sulfuric acid resulted only in partial stimulation of gentamicin biosynthesis. Simultaneous addition of sulfuric acid ammonium nitrate which suppressed the antibiotic biosynthesis when used alone was equal to introduction of ammonium sulfate."}
{"id": "PMID:18982", "title": "[Ways to optimize the technological process of oleandomycin reextraction].", "content": "Dependence of the oleandomycin distribution coefficient on pH of the acqueous phase and temperature in the system of butylacetate extract-water acidified with orthophosphoric acid was studied. With a purpose of intensification of the process of oleandomycin reextraction, decreasing the antibiotic inactivation and evaporation of the organic solvent it was proposed to perfom oleandomycin extraction at pH 4.0--5.0 accompanied by simultaneous decreasing of the temperature.", "contents": "[Ways to optimize the technological process of oleandomycin reextraction]. Dependence of the oleandomycin distribution coefficient on pH of the acqueous phase and temperature in the system of butylacetate extract-water acidified with orthophosphoric acid was studied. With a purpose of intensification of the process of oleandomycin reextraction, decreasing the antibiotic inactivation and evaporation of the organic solvent it was proposed to perfom oleandomycin extraction at pH 4.0--5.0 accompanied by simultaneous decreasing of the temperature."}
{"id": "PMID:18977", "title": "Normal and abnormal middle ear ventilation.", "content": "Studies in infants and children have suggested a functional rather than mechanical obstruction of the Eustachian tube as a predisposing factor in middle ear effusions (MEE). To simulate this condition in the laboratory, an animal model was prepared using juvenile Rhesus monkeys. The tensor veli palatini muscle was transected or expunged posterior to the hamulus of the medial pterygoid lamina. Transection of the muscle resulted in negative middle ear pressure without effusion, whereas when the muscle was expunged, the animals developed a brief episode of negative middle ear pressure followed by a persistent MEE that was sterile for bacteria. An acute bacterial MEE developed following instillation of Streptococcus pneumoniae into the nasopharynx of animals that had had a previous unilateral transection of the muscle. The condition of the middle ear was documented by impedance measurements and presence of the effusion was verified by myringotomy. Animals were periodically examined and tested for Eustachian tube ventilatory function over a period of one year. Before surgical alteration of the tensor muscle. Eustachian tube function tests demonstrated normal ventilatory function, whereas, functional Eustachian tube obstruction patterns similar to studies in children who had MEE were found during the postoperative period. Only after the development of a reliable animal model can current and future methods of management of MEE be tested under controlled laboratory conditions. These data suggest that the Rhesus monkey appears to be an excellent model for the study of normal as well as abnormal tubal function.", "contents": "Normal and abnormal middle ear ventilation. Studies in infants and children have suggested a functional rather than mechanical obstruction of the Eustachian tube as a predisposing factor in middle ear effusions (MEE). To simulate this condition in the laboratory, an animal model was prepared using juvenile Rhesus monkeys. The tensor veli palatini muscle was transected or expunged posterior to the hamulus of the medial pterygoid lamina. Transection of the muscle resulted in negative middle ear pressure without effusion, whereas when the muscle was expunged, the animals developed a brief episode of negative middle ear pressure followed by a persistent MEE that was sterile for bacteria. An acute bacterial MEE developed following instillation of Streptococcus pneumoniae into the nasopharynx of animals that had had a previous unilateral transection of the muscle. The condition of the middle ear was documented by impedance measurements and presence of the effusion was verified by myringotomy. Animals were periodically examined and tested for Eustachian tube ventilatory function over a period of one year. Before surgical alteration of the tensor muscle. Eustachian tube function tests demonstrated normal ventilatory function, whereas, functional Eustachian tube obstruction patterns similar to studies in children who had MEE were found during the postoperative period. Only after the development of a reliable animal model can current and future methods of management of MEE be tested under controlled laboratory conditions. These data suggest that the Rhesus monkey appears to be an excellent model for the study of normal as well as abnormal tubal function."}
{"id": "PMID:18983", "title": "[Role of the functional groups of the sibiromycin molecule in DNA binding].", "content": "Biological activity of 2 derivatives of sibiromycin, an antibiotic close by its chemical structure to antramycin and their capacity for formation of complexes with DNA was studied. Anhydrosibiromycin like sibiromycin formed a complex with DNA. The antibiotic increased the DNA melting point but to a less extent than sibiromycin. Anhydrosibiromycin had a low activity in the system of DNA-dependent RNA-polymerase. The low biological activity of anhydrosibiromycin must be due to instability of the antibiotic complex with DNA. Methyl ether of sibiromycin by the phenol hydroxyl, the other derivative of sibiromycin had no biological activity and did not interact with DNA. On the basis of experimental data it was suggested that definite functional groups of the sibiromycin participated in DNA binding.", "contents": "[Role of the functional groups of the sibiromycin molecule in DNA binding]. Biological activity of 2 derivatives of sibiromycin, an antibiotic close by its chemical structure to antramycin and their capacity for formation of complexes with DNA was studied. Anhydrosibiromycin like sibiromycin formed a complex with DNA. The antibiotic increased the DNA melting point but to a less extent than sibiromycin. Anhydrosibiromycin had a low activity in the system of DNA-dependent RNA-polymerase. The low biological activity of anhydrosibiromycin must be due to instability of the antibiotic complex with DNA. Methyl ether of sibiromycin by the phenol hydroxyl, the other derivative of sibiromycin had no biological activity and did not interact with DNA. On the basis of experimental data it was suggested that definite functional groups of the sibiromycin participated in DNA binding."}
{"id": "PMID:18984", "title": "[Antibiotic sensitivity of the bacterial microflora from the sputum of children with acute pneumonia].", "content": "Bacteriological analysis of sputum of 598 children with acute pneumonia was performed. Sensivity of 1348 cultures belonging to 8 bacterial species with respect to benzylpenicillin, streptomycin, chloramphenicol, tetracycline, oxytetracycline, chlortetracycline, erythromycin, oleandomycin, neomycin and monomycin was determined. It was shown that the sputum microflora was often resistant to the antibiotics widely used in the medical practice for prolonged periods of time, such as benzylpenicillin, streptomycin, chloramphenicol, tetracyclines. However, it usually remained sunsitive to neomycin, monomycin, erythromycin and oleandomycin. It was found that antibioticogrammes defining the antibiotic choice were of great significance for therapy of acute pneumonia.", "contents": "[Antibiotic sensitivity of the bacterial microflora from the sputum of children with acute pneumonia]. Bacteriological analysis of sputum of 598 children with acute pneumonia was performed. Sensivity of 1348 cultures belonging to 8 bacterial species with respect to benzylpenicillin, streptomycin, chloramphenicol, tetracycline, oxytetracycline, chlortetracycline, erythromycin, oleandomycin, neomycin and monomycin was determined. It was shown that the sputum microflora was often resistant to the antibiotics widely used in the medical practice for prolonged periods of time, such as benzylpenicillin, streptomycin, chloramphenicol, tetracyclines. However, it usually remained sunsitive to neomycin, monomycin, erythromycin and oleandomycin. It was found that antibioticogrammes defining the antibiotic choice were of great significance for therapy of acute pneumonia."}
{"id": "PMID:18985", "title": "Activity of spectinomycin against anaerobes.", "content": "The in vitro inhibitory activity of spectinomycin was tested against various anaerobic bacteria. Different results were obtained with different media and with different initial pH's of the media. The highest minimum inhibitory concentrations for Bacteroides fragilis ([Formula: see text] 128 mug/ml) were obtained with the use of Wilkins-Chalgren agar (pH 7.2) and Brucella blood agar (pH 7.0). Brucella blood agar at higher pH's (7.4 and 8.0) and Mueller-Hinton and Diagnostic Sensitivity Test agars produced lower minimum inhibitory concentrations (32 and 64 mug/ml). This same relationship between spectinomycin activity and pH of the medium was, in general, observed with these media and other anaerobes, including isolates of B. melaninogenicus, Fusobacterium, gram-positive cocci, Clostridium perfringens, and C. ramosum. The variable results observed in this study and in two others make it difficult to predict the clinical usefulness of spectinomycin in the treatment of anaerobic infections. It is probably most appropriate to be guided by results obtained with Wilkins-Chalgren agar and the method proposed as a reference to the National Committee for Clinical Laboratory Standards. These results indicate that spectinomycin is not a potent inhibitor of B. fragilis or other clinically significant anaerobes.", "contents": "Activity of spectinomycin against anaerobes. The in vitro inhibitory activity of spectinomycin was tested against various anaerobic bacteria. Different results were obtained with different media and with different initial pH's of the media. The highest minimum inhibitory concentrations for Bacteroides fragilis ([Formula: see text] 128 mug/ml) were obtained with the use of Wilkins-Chalgren agar (pH 7.2) and Brucella blood agar (pH 7.0). Brucella blood agar at higher pH's (7.4 and 8.0) and Mueller-Hinton and Diagnostic Sensitivity Test agars produced lower minimum inhibitory concentrations (32 and 64 mug/ml). This same relationship between spectinomycin activity and pH of the medium was, in general, observed with these media and other anaerobes, including isolates of B. melaninogenicus, Fusobacterium, gram-positive cocci, Clostridium perfringens, and C. ramosum. The variable results observed in this study and in two others make it difficult to predict the clinical usefulness of spectinomycin in the treatment of anaerobic infections. It is probably most appropriate to be guided by results obtained with Wilkins-Chalgren agar and the method proposed as a reference to the National Committee for Clinical Laboratory Standards. These results indicate that spectinomycin is not a potent inhibitor of B. fragilis or other clinically significant anaerobes."}
{"id": "PMID:18986", "title": "Differential susceptibility of spleen focus-forming virus and murine leukemia viruses to ansamycin antibiotics.", "content": "The streptovaricin complex (SvCx) and rifamycin SV derivatives display potent antiviral activity against the polycythemic strain of Friend leukemia virus (FV-P), as measured by a reduction in the number of spleen foci produced in mice. Such reductions may be explained by inactivation of functions of (i) the spleen focus-forming virus (SFFV), (ii) its \"helper\" murine leukemia virus (MuLV), or (iii) both viruses normally present in FV-P. We noted that preincubation of FV-P with fractionation products of SvCx, or derivatives of rifamycin SV, at low concentrations (3 to 5 mug/ml) reduces the number of spleen foci 80 to 97%, whereas titers of MuLV (from the same inoculum) remain unaffected (MuLV titers were measured by XC, S(+)L(-), and \"helper activity\" assays). Our findings indicate a remarkable biological selectivity of ansamycins, as well as nonansamycin components of SvCx, against the transforming and defective spleen focus-forming virus as compared to MuLV. Thus, the drugs might be useful in distinguishing other types of oncornaviruses.", "contents": "Differential susceptibility of spleen focus-forming virus and murine leukemia viruses to ansamycin antibiotics. The streptovaricin complex (SvCx) and rifamycin SV derivatives display potent antiviral activity against the polycythemic strain of Friend leukemia virus (FV-P), as measured by a reduction in the number of spleen foci produced in mice. Such reductions may be explained by inactivation of functions of (i) the spleen focus-forming virus (SFFV), (ii) its \"helper\" murine leukemia virus (MuLV), or (iii) both viruses normally present in FV-P. We noted that preincubation of FV-P with fractionation products of SvCx, or derivatives of rifamycin SV, at low concentrations (3 to 5 mug/ml) reduces the number of spleen foci 80 to 97%, whereas titers of MuLV (from the same inoculum) remain unaffected (MuLV titers were measured by XC, S(+)L(-), and \"helper activity\" assays). Our findings indicate a remarkable biological selectivity of ansamycins, as well as nonansamycin components of SvCx, against the transforming and defective spleen focus-forming virus as compared to MuLV. Thus, the drugs might be useful in distinguishing other types of oncornaviruses."}
{"id": "PMID:18987", "title": "Effects of small-particle aerosols of rimantadine and ribavirin on arterial blood pH and gas tensions and lung water content of A2 influenza-infected mice.", "content": "The respiratory pathophysiology of A2 influenza infection was studied in mice treated with small-particle aerosols (SPA) of rimantadine or ribavirin. Untreated infections in mice resulted in survival rates of 15% or less and were characterized by (i) severe hypoventilation (decreased P(O2) and increased P(CO2)), (ii) compensated respiratory acidosis (increased P(CO2) and HCO(3) (-), with normal pH), (iii) pneumonia with increased ratio of wet/dry lung weight, and (iv) hypothermia. Treatment with SPA of rimantadine (21 mg/kg per day for 4 days) beginning 72 h after virus challenge significantly improved survival rate (80%) but failed to alter lung pathology from that found in infected, untreated mice. Rimantadine treatment decreased somewhat the severity of hypoventilation, respiratory acidosis, lung wet weight, hypothermia, and lung virus titers from that observed in infected, untreated mice. SPA of ribavirin (26 mg/kg per day for 4 days) initiated 6 h after SPA exposure of mice to virus significantly improved survival rate (95%) and reduced lung virus titers and lung pathology. Gas exchange and pulmonary edema in ribavirin-treated, infected mice were significantly improved over those of infected, untreated controls. The mechanisms for increased survival rates induced by SPA of rimantadine remain uncertain, since increased survival rates could not be ascribed entirely to improvements in lung functions. In contrast, however, ribavirin treatment appeared to improve survival rates by reducing major lung pathology and pulmonary dysfunction. This was probably mediated through the antiviral effects of ribavirin.", "contents": "Effects of small-particle aerosols of rimantadine and ribavirin on arterial blood pH and gas tensions and lung water content of A2 influenza-infected mice. The respiratory pathophysiology of A2 influenza infection was studied in mice treated with small-particle aerosols (SPA) of rimantadine or ribavirin. Untreated infections in mice resulted in survival rates of 15% or less and were characterized by (i) severe hypoventilation (decreased P(O2) and increased P(CO2)), (ii) compensated respiratory acidosis (increased P(CO2) and HCO(3) (-), with normal pH), (iii) pneumonia with increased ratio of wet/dry lung weight, and (iv) hypothermia. Treatment with SPA of rimantadine (21 mg/kg per day for 4 days) beginning 72 h after virus challenge significantly improved survival rate (80%) but failed to alter lung pathology from that found in infected, untreated mice. Rimantadine treatment decreased somewhat the severity of hypoventilation, respiratory acidosis, lung wet weight, hypothermia, and lung virus titers from that observed in infected, untreated mice. SPA of ribavirin (26 mg/kg per day for 4 days) initiated 6 h after SPA exposure of mice to virus significantly improved survival rate (95%) and reduced lung virus titers and lung pathology. Gas exchange and pulmonary edema in ribavirin-treated, infected mice were significantly improved over those of infected, untreated controls. The mechanisms for increased survival rates induced by SPA of rimantadine remain uncertain, since increased survival rates could not be ascribed entirely to improvements in lung functions. In contrast, however, ribavirin treatment appeared to improve survival rates by reducing major lung pathology and pulmonary dysfunction. This was probably mediated through the antiviral effects of ribavirin."}
{"id": "PMID:18988", "title": "Delineation of the relative antibacterial activity of cefamandole and cefamandole nafate.", "content": "By conventional laboratory evaluation procedures, the in vitro antibacterial activities of cefamandole and its O-formyl ester, cefamandole nafate, appear virtually identical. When the activities of these two compounds were examined for their ability to lyse log-phase cultures of susceptible bacteria, however, cefamandole was found to be about 10 times more active than cefamandole nafate. Cefamandole nafate was shown to be rapidly converted to cefamandole in bacteriological media, with a half-life of less than 1 h at a pH of 7.0 or above. At pH 6.0, in log-phase inhibition experiments, however, cefamandole nafate is more stable, allowing delineation of the activity between cefamandole and cefamandole nafate. The efficacy of cefamandole was identical to that of cefamandole nafate in treating experimental animal infections, indicating that rapid conversion of cefamandole nafate to cefamandole occurs in vivo.", "contents": "Delineation of the relative antibacterial activity of cefamandole and cefamandole nafate. By conventional laboratory evaluation procedures, the in vitro antibacterial activities of cefamandole and its O-formyl ester, cefamandole nafate, appear virtually identical. When the activities of these two compounds were examined for their ability to lyse log-phase cultures of susceptible bacteria, however, cefamandole was found to be about 10 times more active than cefamandole nafate. Cefamandole nafate was shown to be rapidly converted to cefamandole in bacteriological media, with a half-life of less than 1 h at a pH of 7.0 or above. At pH 6.0, in log-phase inhibition experiments, however, cefamandole nafate is more stable, allowing delineation of the activity between cefamandole and cefamandole nafate. The efficacy of cefamandole was identical to that of cefamandole nafate in treating experimental animal infections, indicating that rapid conversion of cefamandole nafate to cefamandole occurs in vivo."}
{"id": "PMID:18989", "title": "Rapid induction of alpha-amylase by nongrowing mycelia of Aspergillus oryzae.", "content": "A rapid induction system for synthesis of alpha-amylase by the funga Aspergillus oryzae M-13 was established. The mycelia were prepared from 20-h cultures grown on a peptone-glycerol medium and starved for 5 h; maltose was the optimum inducer tested. During h 1 of induction, formation of both intra- and extracellular alpha-amylases occurred at an almost identical rate (70 to 80 microgram/g of cells-h) without a detectable lag period. After a 1-h induction period, a remarkable increase in the extracellular concentration of the enzyme occurred, and a maximum rate (330 microgram/g of cells-h) was reached after 1.5 h of induction. During h 2 of induction, no significant change in mycelial weight was observed. Purified samples of intra- and extracellular enzymes formed in the induction system showed identical properties as examined by behavior in diethylaminoethyl-cellulose column chromatography, gel filtration, discontinuous gel electrophoresis, electrofocusing, optimal conditions for the reaction, heat stability, and molecular weight.", "contents": "Rapid induction of alpha-amylase by nongrowing mycelia of Aspergillus oryzae. A rapid induction system for synthesis of alpha-amylase by the funga Aspergillus oryzae M-13 was established. The mycelia were prepared from 20-h cultures grown on a peptone-glycerol medium and starved for 5 h; maltose was the optimum inducer tested. During h 1 of induction, formation of both intra- and extracellular alpha-amylases occurred at an almost identical rate (70 to 80 microgram/g of cells-h) without a detectable lag period. After a 1-h induction period, a remarkable increase in the extracellular concentration of the enzyme occurred, and a maximum rate (330 microgram/g of cells-h) was reached after 1.5 h of induction. During h 2 of induction, no significant change in mycelial weight was observed. Purified samples of intra- and extracellular enzymes formed in the induction system showed identical properties as examined by behavior in diethylaminoethyl-cellulose column chromatography, gel filtration, discontinuous gel electrophoresis, electrofocusing, optimal conditions for the reaction, heat stability, and molecular weight."}
{"id": "PMID:18990", "title": "Effect of storage time and temperature on the survival of Clostridium botulinum spores in acid media.", "content": "Clostridium-botulinum type A and type B spores were stored in tomato juice (pH 4.2) and citric acid-phosphate buffer (pH 4.2) at 4, 22, and 32 degrees C for 180 days. The spore count was determined at different intervals over the 180-day storage period. There was no significant decrease in the number of type A spores in either the tomato juice or citric acid-phosphate buffer stored for 180 days at 4, 22, and 32 degrees C. The number of type B spores did not decrease when storage was at 4 degrees C, but there was an approximately 30% decrease in the number of spores after 180 days of storage at 22 and 32 degrees C.", "contents": "Effect of storage time and temperature on the survival of Clostridium botulinum spores in acid media. Clostridium-botulinum type A and type B spores were stored in tomato juice (pH 4.2) and citric acid-phosphate buffer (pH 4.2) at 4, 22, and 32 degrees C for 180 days. The spore count was determined at different intervals over the 180-day storage period. There was no significant decrease in the number of type A spores in either the tomato juice or citric acid-phosphate buffer stored for 180 days at 4, 22, and 32 degrees C. The number of type B spores did not decrease when storage was at 4 degrees C, but there was an approximately 30% decrease in the number of spores after 180 days of storage at 22 and 32 degrees C."}
{"id": "PMID:18997", "title": "Graft-versus-host reaction. Cutaneous manifestations following bone marrow transplantation.", "content": "The distinctive cutaneous changes that occur in both the acute and chronic forms of the graft-vs-host reaction (GVHR) are described in two living patients in whom the GVHR developed after bone marrow transplantation for aplastic anemia. In the skin, the mild form of the acute GVHR is recognized as a subtle macular erythema, and the severe form appears as erythematous papules and violaceous macules with scale. Skin biopsy specimens in both of the acute forms show vacuolar alterations of the epidermal basal-cell layer with a perivenular infiltrate of lymphocytes. The chronic GVHR evolves from generalized scaling to diffuse areas of aclerotic and atrophic skin with a curious reticulated hyperpigmentation, ulcerations, and alopecia. Histopathologic study shows collagenization of the dermis that can be correlated with the clinical sclerodermoid changes. Owing to its visibility, the skin offers a unique opportunity for the early recognition of the GVHR.", "contents": "Graft-versus-host reaction. Cutaneous manifestations following bone marrow transplantation. The distinctive cutaneous changes that occur in both the acute and chronic forms of the graft-vs-host reaction (GVHR) are described in two living patients in whom the GVHR developed after bone marrow transplantation for aplastic anemia. In the skin, the mild form of the acute GVHR is recognized as a subtle macular erythema, and the severe form appears as erythematous papules and violaceous macules with scale. Skin biopsy specimens in both of the acute forms show vacuolar alterations of the epidermal basal-cell layer with a perivenular infiltrate of lymphocytes. The chronic GVHR evolves from generalized scaling to diffuse areas of aclerotic and atrophic skin with a curious reticulated hyperpigmentation, ulcerations, and alopecia. Histopathologic study shows collagenization of the dermis that can be correlated with the clinical sclerodermoid changes. Owing to its visibility, the skin offers a unique opportunity for the early recognition of the GVHR."}
{"id": "PMID:19000", "title": "The salt relations of Dunaliella. Further observations on glycerol production and its regulation.", "content": "Dunaliella tertiolecta (marine) and D. viridis (halophilic) were each trained by serial transfer to grow at salt concentrations previously regarded as the other's domain. D. viridis then had a salt optimum at 1.0-1.5 M sodium chloride whereas that for D. tertiolecta was less than 0-2 M. Nevertheless D. tertiolecta grew faster than the halophil at all salt concentrations up to 3.5 M, the highest at which they were compared. Both species accumulate glycerol, which is necessary for growth at elevated salinities and which responds in its content to water activity (aw) rather than specifically to salt concentration. Variation in glycerol content is a metabolic process which occurs in the dark from accumulated starch as well as photosynthetically. Regulation of glycerol content by aw does not require protein synthesis. The NADP-specific glycerol dehydrogenase of each of the algae is likely to be directly involved in the regulation of glycerol content. Kinetic studies, together with those described in an earlier publication, show that the enzyme has regulatory properties and that both glycerol and dihydroxyacetone act as effectors as well as reactants. A mechanism of the reaction is tentatively proposed.", "contents": "The salt relations of Dunaliella. Further observations on glycerol production and its regulation. Dunaliella tertiolecta (marine) and D. viridis (halophilic) were each trained by serial transfer to grow at salt concentrations previously regarded as the other's domain. D. viridis then had a salt optimum at 1.0-1.5 M sodium chloride whereas that for D. tertiolecta was less than 0-2 M. Nevertheless D. tertiolecta grew faster than the halophil at all salt concentrations up to 3.5 M, the highest at which they were compared. Both species accumulate glycerol, which is necessary for growth at elevated salinities and which responds in its content to water activity (aw) rather than specifically to salt concentration. Variation in glycerol content is a metabolic process which occurs in the dark from accumulated starch as well as photosynthetically. Regulation of glycerol content by aw does not require protein synthesis. The NADP-specific glycerol dehydrogenase of each of the algae is likely to be directly involved in the regulation of glycerol content. Kinetic studies, together with those described in an earlier publication, show that the enzyme has regulatory properties and that both glycerol and dihydroxyacetone act as effectors as well as reactants. A mechanism of the reaction is tentatively proposed."}
{"id": "PMID:19001", "title": "[Studies on the thiamine transport system in Bacillus cereus (author's transl)].", "content": "The thiamine transport system in Bacillus cereus exhibits rhythmical changes of resorption- and excretion-phases lasting 1-2 h. These main phases are subdivided in shorter ones with an average duration of 45 s. The velocity of the thiamine uptake is influenced by pH, temperature, age of cells, energy and substrate supply and thiamine concentration of the medium. The Michaelis-Menten-Kinetic can be used to describe the uptake: Km = 1.98 x 10(-8) M; Vmax = 1.19 x 10(-6) mol/g dry weight x min. The rate is enhanced by K+, Ca2+ and Mg2+, and inhibited by Pyrithiamin, EDTA, H+-ions, proton donors and proton acceptors; OH(-)-ions cause a change in the direction of transport. A theoretical explanation can be given by assuming a coupling of the thiamine permeation with proton movements in the membrane.", "contents": "[Studies on the thiamine transport system in Bacillus cereus (author's transl)]. The thiamine transport system in Bacillus cereus exhibits rhythmical changes of resorption- and excretion-phases lasting 1-2 h. These main phases are subdivided in shorter ones with an average duration of 45 s. The velocity of the thiamine uptake is influenced by pH, temperature, age of cells, energy and substrate supply and thiamine concentration of the medium. The Michaelis-Menten-Kinetic can be used to describe the uptake: Km = 1.98 x 10(-8) M; Vmax = 1.19 x 10(-6) mol/g dry weight x min. The rate is enhanced by K+, Ca2+ and Mg2+, and inhibited by Pyrithiamin, EDTA, H+-ions, proton donors and proton acceptors; OH(-)-ions cause a change in the direction of transport. A theoretical explanation can be given by assuming a coupling of the thiamine permeation with proton movements in the membrane."}
{"id": "PMID:18998", "title": "Nitrogen dioxide and pulmonary proteolytic enzymes. Effect on lung tissue and macrophages.", "content": "Hamsters were exposed to 30 ppm nitrogen dioxide (NO2) for 2 and 50 days and sacrificed. Pulmonary lavage was carried out on a portion of each group to obtain an alveolar macrophage fraction. Proteolytic activity (P.A.), as measured by caseinolysis at pH 3.0 and pH 5.0, increased nearly twofold in the 2-day NO2 lung extracts and fourfold in the 50-day NO2 samples. P.A. in macrophage extract at pH 3.0 increased tenfold with both 2- and 50-day NO2 exposure. Lung extract hydrolysis of specific esterase and amidase substrates and susceptibility to activators and inhibitors of proteolytic enzymes are consistent with the presence of lysosomal cathepsin A, B1, B2, C, D, and E. The lack of NO2-induced increases in P.A. at physiologic values of pH may be the basis of the lack of significant pulmonary tissue destruction observed in rodents exposed to NO2 for 2 and 50 days.", "contents": "Nitrogen dioxide and pulmonary proteolytic enzymes. Effect on lung tissue and macrophages. Hamsters were exposed to 30 ppm nitrogen dioxide (NO2) for 2 and 50 days and sacrificed. Pulmonary lavage was carried out on a portion of each group to obtain an alveolar macrophage fraction. Proteolytic activity (P.A.), as measured by caseinolysis at pH 3.0 and pH 5.0, increased nearly twofold in the 2-day NO2 lung extracts and fourfold in the 50-day NO2 samples. P.A. in macrophage extract at pH 3.0 increased tenfold with both 2- and 50-day NO2 exposure. Lung extract hydrolysis of specific esterase and amidase substrates and susceptibility to activators and inhibitors of proteolytic enzymes are consistent with the presence of lysosomal cathepsin A, B1, B2, C, D, and E. The lack of NO2-induced increases in P.A. at physiologic values of pH may be the basis of the lack of significant pulmonary tissue destruction observed in rodents exposed to NO2 for 2 and 50 days."}
{"id": "PMID:19002", "title": "Utilization of nitrogen compounds and ammonia assimilation by Chromatiaceae.", "content": "Chromatium vinosum strain D, Thiocapsa roseopersicina strain 6311 and Ectothiorhodospira mobilis strain 8112 were grown anaerobically in the light with various single nitrogen sources. When substituted for NH4Cl only glutamine and casamino acids supported good growth of all strains tested. Peptone and urea were utilized by C. vinosum and T. roseopersicina, glutamate, asparagine and nitrate only by C. vinosum. The strains were able to grow with molecular nitrogen; complete inhibition of this growth was observed in the presence of alanine with E. mobilis, and of alanine or asparagine with T. roseopersicina. Glutamate dehydrogenase, requiring either NADH or NADPH, NADH-linked glutamate synthase, and glutamine synthetase were demonstrated in the above organisms grown on NH4Cl.", "contents": "Utilization of nitrogen compounds and ammonia assimilation by Chromatiaceae. Chromatium vinosum strain D, Thiocapsa roseopersicina strain 6311 and Ectothiorhodospira mobilis strain 8112 were grown anaerobically in the light with various single nitrogen sources. When substituted for NH4Cl only glutamine and casamino acids supported good growth of all strains tested. Peptone and urea were utilized by C. vinosum and T. roseopersicina, glutamate, asparagine and nitrate only by C. vinosum. The strains were able to grow with molecular nitrogen; complete inhibition of this growth was observed in the presence of alanine with E. mobilis, and of alanine or asparagine with T. roseopersicina. Glutamate dehydrogenase, requiring either NADH or NADPH, NADH-linked glutamate synthase, and glutamine synthetase were demonstrated in the above organisms grown on NH4Cl."}
{"id": "PMID:19004", "title": "Substitute and alternative neurotransmitters in neuropsychiatric illness.", "content": "The accumulation of structural analogs of normal synaptic neurotransmitters (substitute or \"false\" neurotransmitters) can have profound behavioral and neurologic consequences. Such abnormalities of the metabolism of amines and amino acids may explain behavioral and neurologic changes in hepatic failure. Accumulations of substitute transmitters may mediate other neuropsychiatric phenomena in states of inborn or acquired metabolic error or after certain drugs associated with psychosis. In developing hypotheses concerning relationships between neuropsychiatric disorders and neurotransmitter metabolism, this mechanism might be considered as a novel approach.", "contents": "Substitute and alternative neurotransmitters in neuropsychiatric illness. The accumulation of structural analogs of normal synaptic neurotransmitters (substitute or \"false\" neurotransmitters) can have profound behavioral and neurologic consequences. Such abnormalities of the metabolism of amines and amino acids may explain behavioral and neurologic changes in hepatic failure. Accumulations of substitute transmitters may mediate other neuropsychiatric phenomena in states of inborn or acquired metabolic error or after certain drugs associated with psychosis. In developing hypotheses concerning relationships between neuropsychiatric disorders and neurotransmitter metabolism, this mechanism might be considered as a novel approach."}
{"id": "PMID:19005", "title": "[Aminoacid-p-nitroanilides splitting activities in the mature human placenta (author's transl)].", "content": "A long experience in the treatment of endometrial cancer shows that the therapeutic measures vary considerably with regard to the extention of the tumor, the age of the patient and her general condition. This circumstances and particularly the critical study of the therapeutical results give the limits, within a certain kind of operation can reasonably be recommended. The intercurrent deaths are an important factor in the statistical evaluation of therapeutical success. As long as the tumor is limited to the body of the uterus, the corrected 5-year recoveries are about 90%. Considering all the circumstances, it becomes obvious, that in this stage, the simple abdominal hysterectomy with removal of the adnexa is still the operation of choice. Beside the histological degree of differentiation, the depth of the muscular invasion is the most important prognostic factor which might lead to additional measures. Postoperative radiation therapy of the vagina reduces considerably the incidence possibility of vaginal apex recurrence. In stage II radical hysterectomy must be considered, although we are aware of the fact, that a simple hysterectomy and bilateral salpingo-oophorectomy combined with radiation treatment may yield just as good results. In the clinical stage III laparotomy ought to be used more frequently. Also in case of operative intervention additional radiotherapy is mostly useful.", "contents": "[Aminoacid-p-nitroanilides splitting activities in the mature human placenta (author's transl)]. A long experience in the treatment of endometrial cancer shows that the therapeutic measures vary considerably with regard to the extention of the tumor, the age of the patient and her general condition. This circumstances and particularly the critical study of the therapeutical results give the limits, within a certain kind of operation can reasonably be recommended. The intercurrent deaths are an important factor in the statistical evaluation of therapeutical success. As long as the tumor is limited to the body of the uterus, the corrected 5-year recoveries are about 90%. Considering all the circumstances, it becomes obvious, that in this stage, the simple abdominal hysterectomy with removal of the adnexa is still the operation of choice. Beside the histological degree of differentiation, the depth of the muscular invasion is the most important prognostic factor which might lead to additional measures. Postoperative radiation therapy of the vagina reduces considerably the incidence possibility of vaginal apex recurrence. In stage II radical hysterectomy must be considered, although we are aware of the fact, that a simple hysterectomy and bilateral salpingo-oophorectomy combined with radiation treatment may yield just as good results. In the clinical stage III laparotomy ought to be used more frequently. Also in case of operative intervention additional radiotherapy is mostly useful."}
{"id": "PMID:19006", "title": "[Aminoacid-p-nitroanilides splitting activities in the mouse human placenta (author's transl)].", "content": "Proteolytic activities of human placental extract are determined with the aid of a sensitive micromethod, based upon the Bratton-Marshall-reaction, and aminoacid-p-nitroanilides as substrates. The activities are differentiated by using 19 substrates, by adding 10 effectors, and by incubating the assays within the pH-range from 6.0--8.4. Besides Oxitocinase- and Aminopeptidase-like activities, a very active neutral peptidase, so far unknown in human placenta, an acid peptidase, e.g. Cathepsin C or Dipeptide-aminopeptidase II, and some other enzymes, not yet indentified by us, are demonstrated.", "contents": "[Aminoacid-p-nitroanilides splitting activities in the mouse human placenta (author's transl)]. Proteolytic activities of human placental extract are determined with the aid of a sensitive micromethod, based upon the Bratton-Marshall-reaction, and aminoacid-p-nitroanilides as substrates. The activities are differentiated by using 19 substrates, by adding 10 effectors, and by incubating the assays within the pH-range from 6.0--8.4. Besides Oxitocinase- and Aminopeptidase-like activities, a very active neutral peptidase, so far unknown in human placenta, an acid peptidase, e.g. Cathepsin C or Dipeptide-aminopeptidase II, and some other enzymes, not yet indentified by us, are demonstrated."}
{"id": "PMID:19007", "title": "Activities of some peptidases and glycolytic enzymes in cells of the amniotic fluid. i. Pregnancies terminated prematurely, at term, and postmaturely.", "content": "Activities of leucylaminopeptidase, gamma-glutamyl transpeptidase, oxytocinase and aldolase were significantly elevated in the cells of amniotic fluids from cases of premature delivery, compared with cases of delivery at term. The authors conclude that examination of the activities of the aforementioned enzymes can be utilized in prenatal diagnosis of the state of maturity of the fetus.", "contents": "Activities of some peptidases and glycolytic enzymes in cells of the amniotic fluid. i. Pregnancies terminated prematurely, at term, and postmaturely. Activities of leucylaminopeptidase, gamma-glutamyl transpeptidase, oxytocinase and aldolase were significantly elevated in the cells of amniotic fluids from cases of premature delivery, compared with cases of delivery at term. The authors conclude that examination of the activities of the aforementioned enzymes can be utilized in prenatal diagnosis of the state of maturity of the fetus."}
{"id": "PMID:19008", "title": "Variables of the rubella hemagglutination tests employing freeze-dried erythrocytes.", "content": "The variables which affect the interaction between freeze-dried one-day-old chick erythrocytes and rubella hemagglutinin prepared from rubella-infected porcine kidney cells were defined and evaluated. The sensitivity of the hemagglutination (HA) reaction is much greater at pH 6.0 to 6.2 than at pH 7.0 to 7.5 HEPES (N-2-hydroxyethylpiperazine-N'-2'-ethanesulfonic acid) diluent with added Ca+ or Mg2+ ion gave four- to eightfold higher HA titers than one without divalent cations. The development of agglutinated and non-agglutinated erythrocyte patterns depended much upon the concentrations of gelatin and albumin in the HEPES diluent. Gelatin especially was essential to obtain stable and clearly distinguishable patterns. Optimal conditions for the agglutination of freeze-dried erythrocytes by rubella hemagglutinin were provided when a HEPES-buffered saline at pH 6.2, containing 10(-3) M CaCl2, 0.2 per cent bovine serum albumin, and 0.0025 per cent gelatin was employed throughout as a diluent for serum, hemagglutinin, and freeze-dried erythrocyte suspension. This diluent gave maximally sensitive and reproducible results in rubella HA and hemagglutination-inhibition (HI) tests employing freeze-dried erythrocytes.", "contents": "Variables of the rubella hemagglutination tests employing freeze-dried erythrocytes. The variables which affect the interaction between freeze-dried one-day-old chick erythrocytes and rubella hemagglutinin prepared from rubella-infected porcine kidney cells were defined and evaluated. The sensitivity of the hemagglutination (HA) reaction is much greater at pH 6.0 to 6.2 than at pH 7.0 to 7.5 HEPES (N-2-hydroxyethylpiperazine-N'-2'-ethanesulfonic acid) diluent with added Ca+ or Mg2+ ion gave four- to eightfold higher HA titers than one without divalent cations. The development of agglutinated and non-agglutinated erythrocyte patterns depended much upon the concentrations of gelatin and albumin in the HEPES diluent. Gelatin especially was essential to obtain stable and clearly distinguishable patterns. Optimal conditions for the agglutination of freeze-dried erythrocytes by rubella hemagglutinin were provided when a HEPES-buffered saline at pH 6.2, containing 10(-3) M CaCl2, 0.2 per cent bovine serum albumin, and 0.0025 per cent gelatin was employed throughout as a diluent for serum, hemagglutinin, and freeze-dried erythrocyte suspension. This diluent gave maximally sensitive and reproducible results in rubella HA and hemagglutination-inhibition (HI) tests employing freeze-dried erythrocytes."}
{"id": "PMID:19011", "title": "Purification of rat liver particulate neutral ribonuclease and comparison of properties with pancreas and serum ribonucleases.", "content": "Rat liver particulate neutral ribonuclease (EC 3.1.4.22) was extensively purified (up to 40000-fold). It is shown to be an endonuclease, specific for pyrimidine bases, hydrolysing 5'-phosphate ester bonds. The enzyme specificity, Km, pH optimum, stability in acid medium and thermal stability at high temperature are the same as those of rat pancreatic and serum ribonucleases. Like pancreatic and serum neutral ribonucleases, the hepatic enzyme is sensitive to the liver natural inhibitor. This inhibitor was purified 8000-fold; its association with ribonuclease follows zero-order kinetics. These identical properties for ribonuclease of rat liver, pancreas and serum support the hypothesis [Bartholeyns, Peeters-Joris & Baudhuin (1975) Eur. J. Biochem. 60, 385-393] of an extrahepatic origin for the liver enzyme, the plasma ribonuclease of pancreatic origin being taken up by endocytosis in the liver. Neutral ribonuclease activity was detected in all rat organs investigated; its distribution among tissues is different from the distribution of the natural ribonuclear inhibitor.", "contents": "Purification of rat liver particulate neutral ribonuclease and comparison of properties with pancreas and serum ribonucleases. Rat liver particulate neutral ribonuclease (EC 3.1.4.22) was extensively purified (up to 40000-fold). It is shown to be an endonuclease, specific for pyrimidine bases, hydrolysing 5'-phosphate ester bonds. The enzyme specificity, Km, pH optimum, stability in acid medium and thermal stability at high temperature are the same as those of rat pancreatic and serum ribonucleases. Like pancreatic and serum neutral ribonucleases, the hepatic enzyme is sensitive to the liver natural inhibitor. This inhibitor was purified 8000-fold; its association with ribonuclease follows zero-order kinetics. These identical properties for ribonuclease of rat liver, pancreas and serum support the hypothesis [Bartholeyns, Peeters-Joris & Baudhuin (1975) Eur. J. Biochem. 60, 385-393] of an extrahepatic origin for the liver enzyme, the plasma ribonuclease of pancreatic origin being taken up by endocytosis in the liver. Neutral ribonuclease activity was detected in all rat organs investigated; its distribution among tissues is different from the distribution of the natural ribonuclear inhibitor."}
{"id": "PMID:19012", "title": "Identification and partial characterization of phospholipases in isolated adrenocortical cells. The effects of synacthen [corticotropin-(1--24)-tetracosapeptide] and calcium ions.", "content": "Phospholipase A activity was determined in homogenates and subcellular fractions of trypsin-dispersed cat adrenocortical cells. At pH 7.4 homogenate phospholipid hydrolysis was activated by added Ca2+ and inhibited by EGTA. Phospholipid degradation in the presence and absence of Synacthen was completely blocked by EGTA. Ca2+-dependent activation of a membrane-bound phospholipase may be a critical control mechanism for regulating the molecular changes taking place during stimulation by Synacthen.", "contents": "Identification and partial characterization of phospholipases in isolated adrenocortical cells. The effects of synacthen [corticotropin-(1--24)-tetracosapeptide] and calcium ions. Phospholipase A activity was determined in homogenates and subcellular fractions of trypsin-dispersed cat adrenocortical cells. At pH 7.4 homogenate phospholipid hydrolysis was activated by added Ca2+ and inhibited by EGTA. Phospholipid degradation in the presence and absence of Synacthen was completely blocked by EGTA. Ca2+-dependent activation of a membrane-bound phospholipase may be a critical control mechanism for regulating the molecular changes taking place during stimulation by Synacthen."}
{"id": "PMID:19013", "title": "A pulse-radiolysis study of the manganese-containing superoxide dismutase from Bacillus stearothermophilus.", "content": "In the preceding paper the mechanism of catalysis of the manganese-containing superoxide dismutase from Bacillus stearothermophilus was shown to involve a 'fast cycle' and a 'slow cycle' [McAdam, Fox, Lavelle & Fielden, 1977 (Biochem. J. 165, 71-79)]. Further properties of the enzyme was considered in the present paper. Pulse-radiolysis studies, under conditions of low substrate concentration to (i.e. when the fast cycle predominates), showed that enzyme activity decreases as pH increases (6.5-10.2). Activity was unaffected by the addition of H2O2 or NaN3 but slightly decreased by KCN. Both H2O2 and the reducing radical anion CO2-- caused a decrease in A480 of the native enzyme. The rate of the fast catalytic cycle was independent of temperature (5-55 degrees C), and as temperature increases the slow cycle becomes relatively more important. Arrhenius parameters of the rate contants were estimated. The possible identity of the various forms of the enzyme is considered.", "contents": "A pulse-radiolysis study of the manganese-containing superoxide dismutase from Bacillus stearothermophilus. In the preceding paper the mechanism of catalysis of the manganese-containing superoxide dismutase from Bacillus stearothermophilus was shown to involve a 'fast cycle' and a 'slow cycle' [McAdam, Fox, Lavelle & Fielden, 1977 (Biochem. J. 165, 71-79)]. Further properties of the enzyme was considered in the present paper. Pulse-radiolysis studies, under conditions of low substrate concentration to (i.e. when the fast cycle predominates), showed that enzyme activity decreases as pH increases (6.5-10.2). Activity was unaffected by the addition of H2O2 or NaN3 but slightly decreased by KCN. Both H2O2 and the reducing radical anion CO2-- caused a decrease in A480 of the native enzyme. The rate of the fast catalytic cycle was independent of temperature (5-55 degrees C), and as temperature increases the slow cycle becomes relatively more important. Arrhenius parameters of the rate contants were estimated. The possible identity of the various forms of the enzyme is considered."}
{"id": "PMID:19014", "title": "Purification and some properties of arylsulphatases A and B from rabbit kidney cortex.", "content": "Arylsulphatases A and B (EC 3.1.6.1) of rabbit kidney cortex were purified 5250- and 7720-fold respectively by a multiple-column-chromatography method. The specific activity toward 4-nitrocatechol sulphate was 42mumol/min per mg  for arylsulphatase A and 62 mumol/min per mg for arylsulphatase B. Each enzyme migrated as a single band on polyacrylamide-gel electrophoresis, and the enzyme activity corresponded to the band of protein on the gel. The rate of hydrolysis of ascorbic acid 2-sulphate by arylsulphatase A was three times that for cerebroside 3-sulphate. Arylsulphatase B hydrolysed UDP-N--acetylgalactosamine 4-sulphate and glucosamine 4,6-disulphate, but not galactosamine 6-sulphate.", "contents": "Purification and some properties of arylsulphatases A and B from rabbit kidney cortex. Arylsulphatases A and B (EC 3.1.6.1) of rabbit kidney cortex were purified 5250- and 7720-fold respectively by a multiple-column-chromatography method. The specific activity toward 4-nitrocatechol sulphate was 42mumol/min per mg  for arylsulphatase A and 62 mumol/min per mg for arylsulphatase B. Each enzyme migrated as a single band on polyacrylamide-gel electrophoresis, and the enzyme activity corresponded to the band of protein on the gel. The rate of hydrolysis of ascorbic acid 2-sulphate by arylsulphatase A was three times that for cerebroside 3-sulphate. Arylsulphatase B hydrolysed UDP-N--acetylgalactosamine 4-sulphate and glucosamine 4,6-disulphate, but not galactosamine 6-sulphate."}
{"id": "PMID:19015", "title": "Purification and properties of a cellulase from Aspergillus niger.", "content": "A cellulolytic enzyme was isolated from a commercial cellulase preparation form Aspergillus niger. A yield of about 50mg of enzyme was obtained per 100g of commerial cellulase. The isolated enzyme was homogeneous in the ultracentrifuge at pH 4.0 and 8.0, and in sodium dodecyl sulphate/polyacrylamide-gel electrophoresis but showed one major and two minor bands in disc gel electrophoresis. No carbohydrate was associated with the protein. Amino acid analysis revealed that the enzyme was rich in acidic and aromatic amino acids. Data from the amino acid composition and dodecyl sulphate/polyacrylamide-gel electrophoresis indicated a molecular weight of 26000. The purified enzyme was active towards CM-cellulose, but no activity towards either cellobiose or p-nitrophenyl beta-D-glucoside was detected under the assay conditions used. The pH optimum for the enzyme was pH 3.8-4.0, and it was stable at 25 degrees C over the range pH 1-9; maximum activity (at pH 4.0) was obtained at 45 degrees C. The cellulase was more stable to heat treatment at pH 8.0 than at 4.0. Kinetic studies gave pK values between 4.2 and 5.3 for groups involved in the enzyme-substrate complex.", "contents": "Purification and properties of a cellulase from Aspergillus niger. A cellulolytic enzyme was isolated from a commercial cellulase preparation form Aspergillus niger. A yield of about 50mg of enzyme was obtained per 100g of commerial cellulase. The isolated enzyme was homogeneous in the ultracentrifuge at pH 4.0 and 8.0, and in sodium dodecyl sulphate/polyacrylamide-gel electrophoresis but showed one major and two minor bands in disc gel electrophoresis. No carbohydrate was associated with the protein. Amino acid analysis revealed that the enzyme was rich in acidic and aromatic amino acids. Data from the amino acid composition and dodecyl sulphate/polyacrylamide-gel electrophoresis indicated a molecular weight of 26000. The purified enzyme was active towards CM-cellulose, but no activity towards either cellobiose or p-nitrophenyl beta-D-glucoside was detected under the assay conditions used. The pH optimum for the enzyme was pH 3.8-4.0, and it was stable at 25 degrees C over the range pH 1-9; maximum activity (at pH 4.0) was obtained at 45 degrees C. The cellulase was more stable to heat treatment at pH 8.0 than at 4.0. Kinetic studies gave pK values between 4.2 and 5.3 for groups involved in the enzyme-substrate complex."}
{"id": "PMID:19025", "title": "Respiratory effects and amnesia after premedication with morphine or lorazepam.", "content": "Lorazepam, a new benzodiazepine, was compared with morphine for premedication. Ten patients received morphine 10 mg/70 kg i.m. and 10 received lorazepam 4 mg/70 kg i.m. Respiratory effects were assessed from the change in slope (S) and intercept (B) of the carbon dioxide response line, using a development of Read's rebreathing method. Morphine depressed S by 47% (P less than 0.01), but after lorazepam S increased by 27% (P less than 0.05), neither drug altering B significantly. In two volunteers lorazepam was assessed by both the rebreathing and the steady-state methods; after lorazepam S was smaller by the steady-state than by the rebreathing technique. The findings for lorazepam are consistent with the known effects of sleep on carbon dioxide sensitivity. Amnesia lasting 4-8 h occurred in all patients who received lorazepam so that pain and nausea during this period were not recalled, but no patient who received morphine experienced amnesia. We conclude that lorazepam merits further study, particularly where sedation without respiratory depression is needed, as in obstetrics, and where amnesia for uncomfortable procedures is required.", "contents": "Respiratory effects and amnesia after premedication with morphine or lorazepam. Lorazepam, a new benzodiazepine, was compared with morphine for premedication. Ten patients received morphine 10 mg/70 kg i.m. and 10 received lorazepam 4 mg/70 kg i.m. Respiratory effects were assessed from the change in slope (S) and intercept (B) of the carbon dioxide response line, using a development of Read's rebreathing method. Morphine depressed S by 47% (P less than 0.01), but after lorazepam S increased by 27% (P less than 0.05), neither drug altering B significantly. In two volunteers lorazepam was assessed by both the rebreathing and the steady-state methods; after lorazepam S was smaller by the steady-state than by the rebreathing technique. The findings for lorazepam are consistent with the known effects of sleep on carbon dioxide sensitivity. Amnesia lasting 4-8 h occurred in all patients who received lorazepam so that pain and nausea during this period were not recalled, but no patient who received morphine experienced amnesia. We conclude that lorazepam merits further study, particularly where sedation without respiratory depression is needed, as in obstetrics, and where amnesia for uncomfortable procedures is required."}
{"id": "PMID:19027", "title": "Correlation of biochemical data with Apgar scores at birth and at one minute.", "content": "A prospective study of 66 unselected neonates revealed a better correlation of umbilical artery blood biochemical data with the Apgar score at birth compared with the score at 1 min. The data confirmed also that inclusion of the score for \"colour\" detracts from the value of the total score. An Apgar score at birth is more valuable than the score at 1 min.", "contents": "Correlation of biochemical data with Apgar scores at birth and at one minute. A prospective study of 66 unselected neonates revealed a better correlation of umbilical artery blood biochemical data with the Apgar score at birth compared with the score at 1 min. The data confirmed also that inclusion of the score for \"colour\" detracts from the value of the total score. An Apgar score at birth is more valuable than the score at 1 min."}
{"id": "PMID:19028", "title": "Cancer of the oral cavity, pharynx/larynx and lung in North Thailand: case-control study and analysis of cigar smoke.", "content": "The unusually high relative frequency of cancer in the laryngeal region in males (18% of all histologically diagnosed cancers) and a sex ratio of unity for lung cancer in Northern Thailand were further explored in a hospital-based case-control study in Chiang Mai. This compared patients having cancers of the oral cavity (including oropharynx), larynx, hypopharynx and lung, with controls in relation to smoking and chewing habits. Statistical analysis indicated that chewing betel is strongly associated with the occurrence of oral cancer in both sexes, and with cancer of the laryngeal region in males. No factors were strongly linked to lung cancer in men, but, in women, urban residence and miang chewing were associated with lung cancer. Analysis of smoke from the two main types of cigars smoked in the region showed that both had high tar content, but there were marked differences in pH. Smoking cigars with alkaline smoke and high tar had an increased risk for laryngeal cancer in males, whereas other cigars with acid smoke and high tar together with manufactured cigarettes had increased risks for lung cancer. These increased risks were not, however, statistically significant.", "contents": "Cancer of the oral cavity, pharynx/larynx and lung in North Thailand: case-control study and analysis of cigar smoke. The unusually high relative frequency of cancer in the laryngeal region in males (18% of all histologically diagnosed cancers) and a sex ratio of unity for lung cancer in Northern Thailand were further explored in a hospital-based case-control study in Chiang Mai. This compared patients having cancers of the oral cavity (including oropharynx), larynx, hypopharynx and lung, with controls in relation to smoking and chewing habits. Statistical analysis indicated that chewing betel is strongly associated with the occurrence of oral cancer in both sexes, and with cancer of the laryngeal region in males. No factors were strongly linked to lung cancer in men, but, in women, urban residence and miang chewing were associated with lung cancer. Analysis of smoke from the two main types of cigars smoked in the region showed that both had high tar content, but there were marked differences in pH. Smoking cigars with alkaline smoke and high tar had an increased risk for laryngeal cancer in males, whereas other cigars with acid smoke and high tar together with manufactured cigarettes had increased risks for lung cancer. These increased risks were not, however, statistically significant."}
{"id": "PMID:19029", "title": "Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patients.", "content": "Previous studies, using plasmapheresis to remove blocking factors of cell-mediated cytotoxicity to melanoma cells from the circulation of melanoma patients, suggested that leucocyte-dependent antibody to melanoma cells may also be blocked by factors in their sera. The present study confirms these findings, by showing that most patients with disseminated melanoma had melanoma LDA activity in the IgG fraction when this was separated from their sera. This also applied to a high percentage of patients with primary melanoma. Evidence that the blocking factors may be immune complexes was shown by experiments in which LDA activity to melanoma cells was revealed after acidification of melanoma sera to dissociate immune complexes, followed by ultrafiltration through membranes retaining molecules of size greater than 100,000 daltons. Blocking of LDA activity in the retentate recurred when the retentate was recombined with the filtrate. Further studies indicated that the blocking activity showed affinity for the target cell and not the effector cell. Preliminary analysis of the specificity of the blocking suggests that this was similar to that of melanoma antisera. These results appear to show that blocking of LDA activity to melanoma cells is common in melanoma patients and that the assay system may provide a quantitative method for their analysis that may yield information of biological importance in the management of melanoma patients.", "contents": "Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patients. Previous studies, using plasmapheresis to remove blocking factors of cell-mediated cytotoxicity to melanoma cells from the circulation of melanoma patients, suggested that leucocyte-dependent antibody to melanoma cells may also be blocked by factors in their sera. The present study confirms these findings, by showing that most patients with disseminated melanoma had melanoma LDA activity in the IgG fraction when this was separated from their sera. This also applied to a high percentage of patients with primary melanoma. Evidence that the blocking factors may be immune complexes was shown by experiments in which LDA activity to melanoma cells was revealed after acidification of melanoma sera to dissociate immune complexes, followed by ultrafiltration through membranes retaining molecules of size greater than 100,000 daltons. Blocking of LDA activity in the retentate recurred when the retentate was recombined with the filtrate. Further studies indicated that the blocking activity showed affinity for the target cell and not the effector cell. Preliminary analysis of the specificity of the blocking suggests that this was similar to that of melanoma antisera. These results appear to show that blocking of LDA activity to melanoma cells is common in melanoma patients and that the assay system may provide a quantitative method for their analysis that may yield information of biological importance in the management of melanoma patients."}
{"id": "PMID:19030", "title": "Serum ferritin in haemochromatosis: changes in the isoferritin composition during venesection therapy.", "content": "The isoferritin composition of serum ferritin in 13 patients with untreated idiopathic haemochromatosis (IHC) has been shown to differ from normal in exhibiting an increase in isoferritins in the pH range 5.54-5.62. A similar change was observed in four patients with gross iron overload secondary to haemolytic anaemia. During the course of venesection therapy there was a progressive rise in isoferritins of pI 5.02-5.06 relative to the more basic isoferritins. These observations are consistent with previous studies showing alterations in tissue isoferritins in untreated IHC before and after venesection therapy and they are compatible with the hypothesis that the more basic isoferritins correspond to a 'storage' ferritin and the more acidic to a 'secretory' ferritin. The studies also provide further evidence for a possible biological role of the individual isoferritins.", "contents": "Serum ferritin in haemochromatosis: changes in the isoferritin composition during venesection therapy. The isoferritin composition of serum ferritin in 13 patients with untreated idiopathic haemochromatosis (IHC) has been shown to differ from normal in exhibiting an increase in isoferritins in the pH range 5.54-5.62. A similar change was observed in four patients with gross iron overload secondary to haemolytic anaemia. During the course of venesection therapy there was a progressive rise in isoferritins of pI 5.02-5.06 relative to the more basic isoferritins. These observations are consistent with previous studies showing alterations in tissue isoferritins in untreated IHC before and after venesection therapy and they are compatible with the hypothesis that the more basic isoferritins correspond to a 'storage' ferritin and the more acidic to a 'secretory' ferritin. The studies also provide further evidence for a possible biological role of the individual isoferritins."}
{"id": "PMID:19031", "title": "Decreased deformability of erythrocytes in haemolytic anaemia associated with glucosephosphate isomerase deficiency.", "content": "Deformability of erythrocytes from four patients with different types of glucosephosphate isomerase (D-glucose-6-phosphate ketoisomerase, GPI) deficiency has been determined by cell filtration. Young as well as whole erythrocyte populations had a markedly increased rigidity and an abnormally strong attachment of haemoglobin to the inner surface of isolated membranes. Acidic environment may enhance membran rigidity in vitro and also during passage of the erythrocytes through the spleen. The decrease of deformability at a pH of 6.8 was most pronounced in the splenectomized patients, and likewise in erythrocytes from the splenic artery, which were obtained from one patient during splenectomy. It is suggested that the metabolic environment of the spleen, with its low pH, impairs the deformability of GPI-deficient erythrocytes and predisposes them to splenic sequestration. The clinical improvement of all patients following splenectomy which is accompanied by an increase of the erythrocyte survival time and by unchanged reticulocyte counts, is in accordance with this view.", "contents": "Decreased deformability of erythrocytes in haemolytic anaemia associated with glucosephosphate isomerase deficiency. Deformability of erythrocytes from four patients with different types of glucosephosphate isomerase (D-glucose-6-phosphate ketoisomerase, GPI) deficiency has been determined by cell filtration. Young as well as whole erythrocyte populations had a markedly increased rigidity and an abnormally strong attachment of haemoglobin to the inner surface of isolated membranes. Acidic environment may enhance membran rigidity in vitro and also during passage of the erythrocytes through the spleen. The decrease of deformability at a pH of 6.8 was most pronounced in the splenectomized patients, and likewise in erythrocytes from the splenic artery, which were obtained from one patient during splenectomy. It is suggested that the metabolic environment of the spleen, with its low pH, impairs the deformability of GPI-deficient erythrocytes and predisposes them to splenic sequestration. The clinical improvement of all patients following splenectomy which is accompanied by an increase of the erythrocyte survival time and by unchanged reticulocyte counts, is in accordance with this view."}
{"id": "PMID:19032", "title": "A to O bone marrow transplantation in severe aplastic anaemia: dynamics of blood group conversion and demonstration of early dyserythropoiesis in the engrafted marrow.", "content": "A to O bone marrow transplantation was performed in a 25-year-old male affected with severe aplastic anaemia, the donor being an HLA compatible brother. Three plasma exchanges had to be performed with an Aminco separator to remove the original and recurring anti-A isohaemagglutinins. The dynamics of O to A blood group conversion were followed by means of differential agglutination. An early wave of marked dyserythropoiesis was observed in the engrafted marrow. Mild to moderate GvHD was treated successfully with MTX, bolus high dosage 6-methylprednisolone and, at relapse, with intravenous ALG.", "contents": "A to O bone marrow transplantation in severe aplastic anaemia: dynamics of blood group conversion and demonstration of early dyserythropoiesis in the engrafted marrow. A to O bone marrow transplantation was performed in a 25-year-old male affected with severe aplastic anaemia, the donor being an HLA compatible brother. Three plasma exchanges had to be performed with an Aminco separator to remove the original and recurring anti-A isohaemagglutinins. The dynamics of O to A blood group conversion were followed by means of differential agglutination. An early wave of marked dyserythropoiesis was observed in the engrafted marrow. Mild to moderate GvHD was treated successfully with MTX, bolus high dosage 6-methylprednisolone and, at relapse, with intravenous ALG."}
{"id": "PMID:19033", "title": "Reciprocal interaction of hemoglobin with oxygen and protons. The influence of allosteric polyanions.", "content": "The interaction of three inositol esters, inositol hexaphosphate (IHP), inositol pentaphosphate (IPP), and inositol hexasulfate (IHS), with hemoglobin has been investigated. The proton uptake method was used to obtain the six binding constants for deoxy- and oxyhemoglobin. These data combined with oxygen binding curves over a range of cofactor concentrations were used to test theoretical and empirical equations relating the affinity of hemoglobin for oxygen and allosteric effectors. The Bohr and Haldane coefficients in the presence of the inositol esters are unequal at low, but not at high, concentration of the cofactors. The maximum value reached by both parameters increases with the number of negative charges of the polyanion. 2,3-Diphosphoglycerate (DPG) differs sharply from the inositol esters since even at high concentrations of this cofactor, the Haldane coefficient remains elevated. This is a reflection of the negligible affinity of DPG for fully oxygenated hemoglobin.", "contents": "Reciprocal interaction of hemoglobin with oxygen and protons. The influence of allosteric polyanions. The interaction of three inositol esters, inositol hexaphosphate (IHP), inositol pentaphosphate (IPP), and inositol hexasulfate (IHS), with hemoglobin has been investigated. The proton uptake method was used to obtain the six binding constants for deoxy- and oxyhemoglobin. These data combined with oxygen binding curves over a range of cofactor concentrations were used to test theoretical and empirical equations relating the affinity of hemoglobin for oxygen and allosteric effectors. The Bohr and Haldane coefficients in the presence of the inositol esters are unequal at low, but not at high, concentration of the cofactors. The maximum value reached by both parameters increases with the number of negative charges of the polyanion. 2,3-Diphosphoglycerate (DPG) differs sharply from the inositol esters since even at high concentrations of this cofactor, the Haldane coefficient remains elevated. This is a reflection of the negligible affinity of DPG for fully oxygenated hemoglobin."}
{"id": "PMID:19034", "title": "Conformations of synthetic tetradecapeptide renin substrate and of angiotensin I in aqueous solution.", "content": "The properties of aqueous solutions of synthetic renin substrate tetradecapeptide (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser) were examined through electrometric titrations, infrared and circular dichroism spectroscopy, and spectrofluorometry. Titration studies of angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) were also made, whose results indicated a flexible folded conformation similar to that previously proposed for the octapeptide angiotensin II, with a possible additional beta turn at the C terminus. The experimental results of the tetradecapeptide study, associated with Chou and Fasman calculations and with an analysis of structure-activity relationships in renin substrates and competitive inhibitors, led to the proposal of a beta turn involving the His-Pro-Phe-His sequence of the tetradecapeptide. This beta turn would be stabilized by beta-antiparallel interaction between residues 3-4 and 10-12 and by electrostatic attraction between the N-terminal ammonium and C-terminal carboxylate groups and would be destabilized below pH 5 by electrostatic repulsion between His6 and His9. The capacity to assume this conformation is related to structural requirements for renin substrates and competitive inhibitors.", "contents": "Conformations of synthetic tetradecapeptide renin substrate and of angiotensin I in aqueous solution. The properties of aqueous solutions of synthetic renin substrate tetradecapeptide (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser) were examined through electrometric titrations, infrared and circular dichroism spectroscopy, and spectrofluorometry. Titration studies of angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) were also made, whose results indicated a flexible folded conformation similar to that previously proposed for the octapeptide angiotensin II, with a possible additional beta turn at the C terminus. The experimental results of the tetradecapeptide study, associated with Chou and Fasman calculations and with an analysis of structure-activity relationships in renin substrates and competitive inhibitors, led to the proposal of a beta turn involving the His-Pro-Phe-His sequence of the tetradecapeptide. This beta turn would be stabilized by beta-antiparallel interaction between residues 3-4 and 10-12 and by electrostatic attraction between the N-terminal ammonium and C-terminal carboxylate groups and would be destabilized below pH 5 by electrostatic repulsion between His6 and His9. The capacity to assume this conformation is related to structural requirements for renin substrates and competitive inhibitors."}
{"id": "PMID:19036", "title": "Effects of quaternary ligands on the inhibition of acetylcholinesterase by arsenite.", "content": "Arsenite inhibits acetylcholinesterase in a second-order reaction. The rate and equilibrium constants depend upon pH and have values on the order of 10(2) M-1 min-1 and 10(5) M (dissociation), respectively. Some quaternary ammonium ligands completely block the arsenite inhibition of the enzyme, others decrease the rate of the reaction and some, notably pyridine-2 aldoxime methiodide, greatly accelerate the rate of the reaction, up to 220-fold. Accelerators may bind at a separate enzyme site distinct form the anionic site involved in substrate binding. Although the kinetic data are consistent with a covalent reaction between arsenite and acetylcholinesterase, chemical evidence excludes the involvement of sulfhydryl groups which are usually implicated in arsenite inhibition.", "contents": "Effects of quaternary ligands on the inhibition of acetylcholinesterase by arsenite. Arsenite inhibits acetylcholinesterase in a second-order reaction. The rate and equilibrium constants depend upon pH and have values on the order of 10(2) M-1 min-1 and 10(5) M (dissociation), respectively. Some quaternary ammonium ligands completely block the arsenite inhibition of the enzyme, others decrease the rate of the reaction and some, notably pyridine-2 aldoxime methiodide, greatly accelerate the rate of the reaction, up to 220-fold. Accelerators may bind at a separate enzyme site distinct form the anionic site involved in substrate binding. Although the kinetic data are consistent with a covalent reaction between arsenite and acetylcholinesterase, chemical evidence excludes the involvement of sulfhydryl groups which are usually implicated in arsenite inhibition."}
{"id": "PMID:19038", "title": "Redox properties of microsomal reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase and cytochrome b5.", "content": "Hepatic NADH-cytochrome b5 reductase was reduced by 1 mol of dithionite or NADH per mol of enzyme-bound FAD, without forming a stable semiquinone or intermediate during the titrations. However, the addition of NAD+ to the partially reduced enzyme or illumination in the presence of both NAD+ and EDTA yielded a new intermediate. The intermediate had an absorption band at 375 nm and the optical spectrum resembled anionic semiquinones seen on reduction of other flavin enzymes. Electron paramagnetic resonance measurements confirmed the free-radical nature of the species. To explain the results, a disproportionation reaction between the oxidized and reduced NAD+ complexes (E-FAD-NAD+ + E-FADH2-NAD+ in equilibrium 2E-FADH.-NAD+) is assumed. Potentiometric titration of NADH-cytochrome b5 reductase at pH 7.0 with dithionite gave a midpoint potential of -258 mV; titration with NADH gave -160 mV. This difference may be due to a difference in the relative affinity of NAD+ for the reduced and oxidized forms of the enzyme. The effects of pH on the midpoint potential of the NAD+-free enzyme were very similar to those which have been measured with free FAD. At pH 7.0, midpoint potentials of trypsin-solubilized and detergent-solubilized cytochrome b5 were 13 and 0 mV, respectively.", "contents": "Redox properties of microsomal reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase and cytochrome b5. Hepatic NADH-cytochrome b5 reductase was reduced by 1 mol of dithionite or NADH per mol of enzyme-bound FAD, without forming a stable semiquinone or intermediate during the titrations. However, the addition of NAD+ to the partially reduced enzyme or illumination in the presence of both NAD+ and EDTA yielded a new intermediate. The intermediate had an absorption band at 375 nm and the optical spectrum resembled anionic semiquinones seen on reduction of other flavin enzymes. Electron paramagnetic resonance measurements confirmed the free-radical nature of the species. To explain the results, a disproportionation reaction between the oxidized and reduced NAD+ complexes (E-FAD-NAD+ + E-FADH2-NAD+ in equilibrium 2E-FADH.-NAD+) is assumed. Potentiometric titration of NADH-cytochrome b5 reductase at pH 7.0 with dithionite gave a midpoint potential of -258 mV; titration with NADH gave -160 mV. This difference may be due to a difference in the relative affinity of NAD+ for the reduced and oxidized forms of the enzyme. The effects of pH on the midpoint potential of the NAD+-free enzyme were very similar to those which have been measured with free FAD. At pH 7.0, midpoint potentials of trypsin-solubilized and detergent-solubilized cytochrome b5 were 13 and 0 mV, respectively."}
{"id": "PMID:19039", "title": "Phosphoglycerate mutase from wheat germ: studies with isotopically labeled 3-phospho-D-glycerates showing that the catalyzed reaction is intramolecular. Appendix: phosphoglycerate mutase from wheat germ: isolation, crystallization, and properties.", "content": "The isomerization of 3-phospho-D-glycerate and 2-phospho-D-glycerate catalyzed by the cofactor-independent phosphoglycerate mutase from wheat germ (the isolation and crystallization of which is described in the Appendix) has been shown to be intramolecular by two methods. Mass-spectrometric analysis of the products from the isomerization of a mixture of 3-phospho-D-[2(-2)H]glycerate and 3-[18O]phospho-D-glycerate shows that there is no exchange of labeled phosphoryl group between carbon skeletons in the mutase-catalyzed reaction. Analysis of the products from the isomerization of a mixture of 3-phospho-D-[2(-2)H]glycerate and 3-[32p]phospho-D-glycerate by a method involving the kinetic discrimination between 2(-2)H and 2(-1)H species using the enolase isotope effect similarly shows that the wheat germ phosphoglycerate mutase mediates an intramolecular transfer of the phosphoryl group.", "contents": "Phosphoglycerate mutase from wheat germ: studies with isotopically labeled 3-phospho-D-glycerates showing that the catalyzed reaction is intramolecular. Appendix: phosphoglycerate mutase from wheat germ: isolation, crystallization, and properties. The isomerization of 3-phospho-D-glycerate and 2-phospho-D-glycerate catalyzed by the cofactor-independent phosphoglycerate mutase from wheat germ (the isolation and crystallization of which is described in the Appendix) has been shown to be intramolecular by two methods. Mass-spectrometric analysis of the products from the isomerization of a mixture of 3-phospho-D-[2(-2)H]glycerate and 3-[18O]phospho-D-glycerate shows that there is no exchange of labeled phosphoryl group between carbon skeletons in the mutase-catalyzed reaction. Analysis of the products from the isomerization of a mixture of 3-phospho-D-[2(-2)H]glycerate and 3-[32p]phospho-D-glycerate by a method involving the kinetic discrimination between 2(-2)H and 2(-1)H species using the enolase isotope effect similarly shows that the wheat germ phosphoglycerate mutase mediates an intramolecular transfer of the phosphoryl group."}
{"id": "PMID:19042", "title": "Preparation and properties of a new DNase from Aspergillus oryzae.", "content": "A DNase present in commercial preparations of Aspergillus oryzae alpha-amylase was purified 1550-fold in 25% yield by acetone precipitation and by chromatography on diethylaminoethyl- and carboxymethylcellulose. The enzyme was isolated free of contaminating RNases and DNases. The molecular weight of the enzyme determined by gel filtration on Sephadex G-100 was 48 000, while a molecular weight of 58 000 was determined for the single band observed upon polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The isoelectric point of the DNase is 9.2. The enzyme hydrolyzed only DNA with a pH optimum of 8.2 and was activated by Co2+, and to a lesser extent by Mg2+ and Mn2+. Native DNA was a better substrate than heat-denatured DNA. Enzymatic digests of calf thymus and E. coli DNA yielded oligomers of chain lengths ranging from 10 to 200, with mono- and small oligonucleotides (chain length less than 5) detected only when large (100 mg) amounts of DNA were fractionated by column chromatography on diethylaminoethyl-Sephadex A-25 in 7 M urea. The digestion products contained 5'-terminal phosphate groups and mostly adenosine at the 3' and guanosine and adenosine at the 5' ends.", "contents": "Preparation and properties of a new DNase from Aspergillus oryzae. A DNase present in commercial preparations of Aspergillus oryzae alpha-amylase was purified 1550-fold in 25% yield by acetone precipitation and by chromatography on diethylaminoethyl- and carboxymethylcellulose. The enzyme was isolated free of contaminating RNases and DNases. The molecular weight of the enzyme determined by gel filtration on Sephadex G-100 was 48 000, while a molecular weight of 58 000 was determined for the single band observed upon polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The isoelectric point of the DNase is 9.2. The enzyme hydrolyzed only DNA with a pH optimum of 8.2 and was activated by Co2+, and to a lesser extent by Mg2+ and Mn2+. Native DNA was a better substrate than heat-denatured DNA. Enzymatic digests of calf thymus and E. coli DNA yielded oligomers of chain lengths ranging from 10 to 200, with mono- and small oligonucleotides (chain length less than 5) detected only when large (100 mg) amounts of DNA were fractionated by column chromatography on diethylaminoethyl-Sephadex A-25 in 7 M urea. The digestion products contained 5'-terminal phosphate groups and mostly adenosine at the 3' and guanosine and adenosine at the 5' ends."}
{"id": "PMID:19044", "title": "Structure-function relationships in TPN-dependent isocitrate dehydrogenase. I. Electron paramagnetic resonance studies of the interaction of enzyme-bound Mn(II) with substrates, cofactors, and substrate analogues.", "content": "Electron paramagnetic resonance (EPR) spectra were obtained for various isocitrate dehydrogenase-Mn(II) complexes. The qualitative effects of the binding of substrates, nucleotides, and substrate analogues on the isotropic character of the electronic environment of enzyme-bound Mn(II) were subsequently investigated. The addition of isocitrate produces a markedly anisotropic spectrum whereas alpha-ketoglutarate does not alter the spectrum of enzyme-Mn(II) substantially. This suggests direct coordination of isocitrate to the Mn(II) but perphaps a different mode of binding for alpha-ketoglutarate. Other studies demonstrated mutually exclusive binding relationships between TPN and TPNH, between Mn-isocitrate and TPNH, and between HCO3-(CO2) and formate or thiocyanate. Indirect evidence supporting CO2 rather than HCO3-as the actual reactive species which binds to the enzyme in the reductive carboxylation reaction is presented on the basis of the results of the formate and thiocyanate studies. From the EPR results recorded for ternary, quaternary, and quinary enzyme-substrate complexes, correlations between the appearance of fine structure signals and the binding of individual substrates and/or nucleotides are found, and tentative assignments of such signals are made on this basis. Additional studies were conducted to determine binding constants for Mg(II) Co(II), and Co-isocitrate, and a comparison was made with kinetically determined binding constants.", "contents": "Structure-function relationships in TPN-dependent isocitrate dehydrogenase. I. Electron paramagnetic resonance studies of the interaction of enzyme-bound Mn(II) with substrates, cofactors, and substrate analogues. Electron paramagnetic resonance (EPR) spectra were obtained for various isocitrate dehydrogenase-Mn(II) complexes. The qualitative effects of the binding of substrates, nucleotides, and substrate analogues on the isotropic character of the electronic environment of enzyme-bound Mn(II) were subsequently investigated. The addition of isocitrate produces a markedly anisotropic spectrum whereas alpha-ketoglutarate does not alter the spectrum of enzyme-Mn(II) substantially. This suggests direct coordination of isocitrate to the Mn(II) but perphaps a different mode of binding for alpha-ketoglutarate. Other studies demonstrated mutually exclusive binding relationships between TPN and TPNH, between Mn-isocitrate and TPNH, and between HCO3-(CO2) and formate or thiocyanate. Indirect evidence supporting CO2 rather than HCO3-as the actual reactive species which binds to the enzyme in the reductive carboxylation reaction is presented on the basis of the results of the formate and thiocyanate studies. From the EPR results recorded for ternary, quaternary, and quinary enzyme-substrate complexes, correlations between the appearance of fine structure signals and the binding of individual substrates and/or nucleotides are found, and tentative assignments of such signals are made on this basis. Additional studies were conducted to determine binding constants for Mg(II) Co(II), and Co-isocitrate, and a comparison was made with kinetically determined binding constants."}
{"id": "PMID:19046", "title": "Purification and properties of a 3'-phosphoryl former endodeoxyribonuclease from eggs of Asterias forbesi.", "content": "A DNA endonuclease has been purified from eggs of Asterias forbesi by a simple four-step-purification procedure. The purified enzyme is at least 96% pure and is free of phosphatase, phosphodiesterase, and RNase. It has a pH optimum of 6.5 and does not require divalent cations. The enzyme produces 3'-phosphoryl and 5'-hydroxyl end groups. The products of exhaustive hydrolysis can be grouped in two fractions. The first fraction, 40%, contains a small amount of mononucleotides and di-, tri-, tetra-, penta-, and hexanucleo-tides. The second fraction, 60%, contains oligonucleotides larger than hexanucleotides.", "contents": "Purification and properties of a 3'-phosphoryl former endodeoxyribonuclease from eggs of Asterias forbesi. A DNA endonuclease has been purified from eggs of Asterias forbesi by a simple four-step-purification procedure. The purified enzyme is at least 96% pure and is free of phosphatase, phosphodiesterase, and RNase. It has a pH optimum of 6.5 and does not require divalent cations. The enzyme produces 3'-phosphoryl and 5'-hydroxyl end groups. The products of exhaustive hydrolysis can be grouped in two fractions. The first fraction, 40%, contains a small amount of mononucleotides and di-, tri-, tetra-, penta-, and hexanucleo-tides. The second fraction, 60%, contains oligonucleotides larger than hexanucleotides."}
{"id": "PMID:19047", "title": "Effect of pH on the interaction of benzoate and D-amino acid oxidase.", "content": "The kinetic and equilibrium dissociation constants of the reversible binding of benzoate to hog kidney D-amino acid oxidase (DAAO) were studied at 19 degrees C over the pH range 5.3-10.5 by means of a stopped-flow apparatus and spectrophotometric titrations. A simple bimolecular reaction of the form second order-first order was observed; a two-step reaction was seen. Analysis of the pH dependence of the bimolecular rate constants and equilibrium dissociation constants is consistent with three ionizable groups which are important for benzoate binding. The pK values of the enzyme-related ionization are 6.3, 9.2, and 9.6. Analysis of the change in extinction coefficient at 360 nm indicates the pK of 9.6 can be assigned to the 3-imino group of the enzyme-bound flavin. The effect of benzoate on the apparent pK for the ionization of the 3-imino group of the enzyme-bound Fad has been reexamined. The presence of benzoate causes an apparent shift of this ionization from a pK value of 9.6 to 10.7.", "contents": "Effect of pH on the interaction of benzoate and D-amino acid oxidase. The kinetic and equilibrium dissociation constants of the reversible binding of benzoate to hog kidney D-amino acid oxidase (DAAO) were studied at 19 degrees C over the pH range 5.3-10.5 by means of a stopped-flow apparatus and spectrophotometric titrations. A simple bimolecular reaction of the form second order-first order was observed; a two-step reaction was seen. Analysis of the pH dependence of the bimolecular rate constants and equilibrium dissociation constants is consistent with three ionizable groups which are important for benzoate binding. The pK values of the enzyme-related ionization are 6.3, 9.2, and 9.6. Analysis of the change in extinction coefficient at 360 nm indicates the pK of 9.6 can be assigned to the 3-imino group of the enzyme-bound flavin. The effect of benzoate on the apparent pK for the ionization of the 3-imino group of the enzyme-bound Fad has been reexamined. The presence of benzoate causes an apparent shift of this ionization from a pK value of 9.6 to 10.7."}
{"id": "PMID:19053", "title": "Pre-steady-state kinetics of intermediate formation in the deuteroferriheme-hydrogen peroxide system.", "content": "The pH dependence of formation of a peroxidatic intermediate from the reaction of deuteroferriheme with hydrogen peroxide has been determined for the region pH 8.7-10.1 from stopped-flow kinetic studies in which absorbancy changes are observed at heme monomer-dimer isosbestic points. Results are interpreted primarily in terms of the attainment of double \"steady-state\" concentrations of Michaelis-Menten complex I and peroxidatic intermediate I'. A linear correlation of observed first-order rate constants with alpha, the degree of dissociation of heme dimer, has been demonstrated and nonzero intercepts are obtained. Slopes and intercepts show a linear logarithmic dependence on pH which is interpreted in terms of HO2-participation both in the formation and subsequent (catalatic) decomposition of a peroxidatically active intermediate. General acid catalysis of intermediate formation is indicated from studies in phosphate, arsenate, and citrate buffer at pH 7.4-9.3. It is suggested that such catalysis may be responsible for anomalously high rates of H2O2 decomposition previously observed in phosphate buffer solution.", "contents": "Pre-steady-state kinetics of intermediate formation in the deuteroferriheme-hydrogen peroxide system. The pH dependence of formation of a peroxidatic intermediate from the reaction of deuteroferriheme with hydrogen peroxide has been determined for the region pH 8.7-10.1 from stopped-flow kinetic studies in which absorbancy changes are observed at heme monomer-dimer isosbestic points. Results are interpreted primarily in terms of the attainment of double \"steady-state\" concentrations of Michaelis-Menten complex I and peroxidatic intermediate I'. A linear correlation of observed first-order rate constants with alpha, the degree of dissociation of heme dimer, has been demonstrated and nonzero intercepts are obtained. Slopes and intercepts show a linear logarithmic dependence on pH which is interpreted in terms of HO2-participation both in the formation and subsequent (catalatic) decomposition of a peroxidatically active intermediate. General acid catalysis of intermediate formation is indicated from studies in phosphate, arsenate, and citrate buffer at pH 7.4-9.3. It is suggested that such catalysis may be responsible for anomalously high rates of H2O2 decomposition previously observed in phosphate buffer solution."}
{"id": "PMID:19054", "title": "Escherichia coli dihydrofolate reductase: isolation and characterization of two isozymes.", "content": "A combination of affinity column chromatography and preparative gel electrophoresis has been used to purify to homogeneity the two isozymes of dihydrofolate reductase from a trimethoprim-resistant strain of Escherichia coli B (RT 500). These enzyme forms are noninterconvertible and are present in crude cell lysates, but other electrophoretic species can be generated durng purification if sulfhydryl-protecting agents, such as dithiothreitol, are not present. The two isozymes, numbered form 1 and form 2 with respect to their decreasing electrophoretic mobilities, have similar molecular weights (18 500), molecular radii (21 A), and apparent Km values for reduced nico inamide adenin- dinucleotide (NADH) and NADH phosphate (NADPH). Both forms contain 2 mol of sulfhydryl/mol of enzyme which can be oxidized to intramolecular disulfide bonds. However, forms 1 and 2 differ physically in their electrophoretic mobility and isoelectric point and kinetically in their pH-activity profile, specific activity, Km for dihydrofolate, and their affinity toward a number of inhibitors.", "contents": "Escherichia coli dihydrofolate reductase: isolation and characterization of two isozymes. A combination of affinity column chromatography and preparative gel electrophoresis has been used to purify to homogeneity the two isozymes of dihydrofolate reductase from a trimethoprim-resistant strain of Escherichia coli B (RT 500). These enzyme forms are noninterconvertible and are present in crude cell lysates, but other electrophoretic species can be generated durng purification if sulfhydryl-protecting agents, such as dithiothreitol, are not present. The two isozymes, numbered form 1 and form 2 with respect to their decreasing electrophoretic mobilities, have similar molecular weights (18 500), molecular radii (21 A), and apparent Km values for reduced nico inamide adenin- dinucleotide (NADH) and NADH phosphate (NADPH). Both forms contain 2 mol of sulfhydryl/mol of enzyme which can be oxidized to intramolecular disulfide bonds. However, forms 1 and 2 differ physically in their electrophoretic mobility and isoelectric point and kinetically in their pH-activity profile, specific activity, Km for dihydrofolate, and their affinity toward a number of inhibitors."}
{"id": "PMID:19055", "title": "Thermal unfolding transition of ribonuclease A measured by 2'-CMP binding.", "content": "We report an approach to the problem of detecting and characterising intermediates in the unfolding of ribonuclease A. Two distinct properties of the protein are compared at equilibrium within the unfolding transition zone: (1) a physical property of the protein, the absorbance of buried tyrosine residues, and (2) a functional property, the ability to bind the specific ligand, 2'-CMP. A direct comparison of these two properties is made within the pH 5.8 transition zone, and an indirect comparison is made by using the stopped-flow instrument to sample rapidly the equilibrium properties of the pH 2.0 transition. At both pH 2.0 and pH 5.8, the results indicate that there are no intermediates in folding which have the physical properties of the native enzyme but which have lost the ability to bind a specific ligand.", "contents": "Thermal unfolding transition of ribonuclease A measured by 2'-CMP binding. We report an approach to the problem of detecting and characterising intermediates in the unfolding of ribonuclease A. Two distinct properties of the protein are compared at equilibrium within the unfolding transition zone: (1) a physical property of the protein, the absorbance of buried tyrosine residues, and (2) a functional property, the ability to bind the specific ligand, 2'-CMP. A direct comparison of these two properties is made within the pH 5.8 transition zone, and an indirect comparison is made by using the stopped-flow instrument to sample rapidly the equilibrium properties of the pH 2.0 transition. At both pH 2.0 and pH 5.8, the results indicate that there are no intermediates in folding which have the physical properties of the native enzyme but which have lost the ability to bind a specific ligand."}
{"id": "PMID:19056", "title": "Partial purification and characterization of an N2-guanine RNA methyltransferase from chicken embryos.", "content": "An N2-guanine RNA methyltransferase has been purified 1000-fold from chick embryo homogenates by phosphocellulose chromatography followed by chromatography on S-adenosylhomocystein-Sepharose. The enzyme was shown to methylate the G10 position of Escherichia coli B tRNAPhe and has a Km of 3X10(-7) M for tRNAPhe and 1.38 X 10(-6) M for S-adenosylmethionine. The molecular weight was estimated to be 77 000 by gel filtration and the pH optimum was 8.0 to 8.5. Magnesium ion was not required for activity but it stimulated the rate of methylation 1.5-fold with an optimum at 12 mM. Ammonium ion stimulated activity about twofold with an optimum at about 83 mM. Sodium and potassium ions above 0.1 M were inhibitory.", "contents": "Partial purification and characterization of an N2-guanine RNA methyltransferase from chicken embryos. An N2-guanine RNA methyltransferase has been purified 1000-fold from chick embryo homogenates by phosphocellulose chromatography followed by chromatography on S-adenosylhomocystein-Sepharose. The enzyme was shown to methylate the G10 position of Escherichia coli B tRNAPhe and has a Km of 3X10(-7) M for tRNAPhe and 1.38 X 10(-6) M for S-adenosylmethionine. The molecular weight was estimated to be 77 000 by gel filtration and the pH optimum was 8.0 to 8.5. Magnesium ion was not required for activity but it stimulated the rate of methylation 1.5-fold with an optimum at 12 mM. Ammonium ion stimulated activity about twofold with an optimum at about 83 mM. Sodium and potassium ions above 0.1 M were inhibitory."}
{"id": "PMID:19063", "title": "Mechanism of pigeon liver malic enzyme modification of histidyl residues by ethoxyformic anhydride.", "content": "Incubation of malic enzyme (L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 1.1.1.40) with ethoxyformic anhydride caused the time-dependent loss of its ability to catalyze reactions requiring the nucleotide cofactor NADP+ or NADPH, such as the oxidative decarboxylase, the NADP+ - stimualted oxalacetate decarboxylase, the pyruvate reductase, and the pyruvate-medium proton exchange activities. Similar loss of oxidative decarboxylase and pyruvate reductase activities was affected by photo-oxidation in the presence of rose bengal. The inactivation of oxidative decarboxylase activity by ethoxyformic anhydride was accompanied by the reaction of greater than or equal to 2.3 histidyl residues per enzyme site and was strongly inhibited by NADP+. Ethoxyformylation also impaired the ability of malic enzyme to bind NADP+ or NADPH. These results support the involvement of histidyl residue(s) at the nucleotide binding site of malic enzyme.", "contents": "Mechanism of pigeon liver malic enzyme modification of histidyl residues by ethoxyformic anhydride. Incubation of malic enzyme (L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC 1.1.1.40) with ethoxyformic anhydride caused the time-dependent loss of its ability to catalyze reactions requiring the nucleotide cofactor NADP+ or NADPH, such as the oxidative decarboxylase, the NADP+ - stimualted oxalacetate decarboxylase, the pyruvate reductase, and the pyruvate-medium proton exchange activities. Similar loss of oxidative decarboxylase and pyruvate reductase activities was affected by photo-oxidation in the presence of rose bengal. The inactivation of oxidative decarboxylase activity by ethoxyformic anhydride was accompanied by the reaction of greater than or equal to 2.3 histidyl residues per enzyme site and was strongly inhibited by NADP+. Ethoxyformylation also impaired the ability of malic enzyme to bind NADP+ or NADPH. These results support the involvement of histidyl residue(s) at the nucleotide binding site of malic enzyme."}
{"id": "PMID:19064", "title": "Characterization of human platelet UDPglucose-collagen glucosyltransferase using a new rapid assay.", "content": "A rapid and specific assay has been developed for UDPglucose-collagen glucosyltransferase (UDPglucose: 5-hydroxylysine-collagen glucosyltransferase, EC 2.4.1.66) using galactosylhydroxylysine (Gal-Hyl) as acceptor. Studies with intact human platelets and isolated plasma membranes indicated that about 5--10% of the total activity was surface bound and the rest was of cytoplasmic origin. The two forms of the enzyme had similar broad pH optima (6.5--8.0), Km values for UDPglucose (5 muM) and Gal-Hyl (approx. 4 mM) and for optimal manganese concentrations (25 mM). The soluble form of the enzyme was purified 80-fold. The reaction mechanism was determined as being rapid equilibrium random BiBi + dead end complex or ordered BiBi with UDPglucose being the first substrate to bind. Using Gal-Hyl bound in purified alpha 1 chain of chick skin collagen, a Km value three orders of magnitude less (2 muM) was found than for free Gal-Hyl and the manganese requirement decreased to 2 mM. These results suggest that the binding to the enzyme of Gal-Hyl in the collagen molecule is enhanced by the presence of the protein portion so that the enzyme may be capable of recognizing not only the carbohydrate side chains but also the primary structure of collagen.", "contents": "Characterization of human platelet UDPglucose-collagen glucosyltransferase using a new rapid assay. A rapid and specific assay has been developed for UDPglucose-collagen glucosyltransferase (UDPglucose: 5-hydroxylysine-collagen glucosyltransferase, EC 2.4.1.66) using galactosylhydroxylysine (Gal-Hyl) as acceptor. Studies with intact human platelets and isolated plasma membranes indicated that about 5--10% of the total activity was surface bound and the rest was of cytoplasmic origin. The two forms of the enzyme had similar broad pH optima (6.5--8.0), Km values for UDPglucose (5 muM) and Gal-Hyl (approx. 4 mM) and for optimal manganese concentrations (25 mM). The soluble form of the enzyme was purified 80-fold. The reaction mechanism was determined as being rapid equilibrium random BiBi + dead end complex or ordered BiBi with UDPglucose being the first substrate to bind. Using Gal-Hyl bound in purified alpha 1 chain of chick skin collagen, a Km value three orders of magnitude less (2 muM) was found than for free Gal-Hyl and the manganese requirement decreased to 2 mM. These results suggest that the binding to the enzyme of Gal-Hyl in the collagen molecule is enhanced by the presence of the protein portion so that the enzyme may be capable of recognizing not only the carbohydrate side chains but also the primary structure of collagen."}
{"id": "PMID:19066", "title": "Cyclic AMP-dependent protein kinase phosphorylation of cardiac (Na+ + K+)-ATPases. Effect on calcium binding.", "content": "1. Calcium binding to (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations from beef and pig heart preparations of varying degrees of purity was measured. 2. Binding was inhibited by Mg2+, Na+ and K+. Inhibition by Na+ and K+ appeared to be due to an ionic strength effect. 3. Four classes of binding sites were identified with Kd values for calcium of about 0.03, 1, 15 and 200 micrometer. 4. Cyclic AMP-dependent phosphorylation of the enzyme by protein kinase (ATP: protamine O-phosphotransferase, EC 2.7.1.70) had no effect on (Na+ + K+)-ATPase activity. 5. Phosphorylation also had no effect on either Kd or Bmax for calcium binding at any of the four sites whether measured in the presence of absence of NaCl or KCl. 6. It is concluded that previous reports of an effect of phosphorylation on calcium binding to a (Na+ + K+)-ATPase preparation may have been due to the presence of membrane material not directly associated with (Na+ + K+)-ATPase.", "contents": "Cyclic AMP-dependent protein kinase phosphorylation of cardiac (Na+ + K+)-ATPases. Effect on calcium binding. 1. Calcium binding to (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations from beef and pig heart preparations of varying degrees of purity was measured. 2. Binding was inhibited by Mg2+, Na+ and K+. Inhibition by Na+ and K+ appeared to be due to an ionic strength effect. 3. Four classes of binding sites were identified with Kd values for calcium of about 0.03, 1, 15 and 200 micrometer. 4. Cyclic AMP-dependent phosphorylation of the enzyme by protein kinase (ATP: protamine O-phosphotransferase, EC 2.7.1.70) had no effect on (Na+ + K+)-ATPase activity. 5. Phosphorylation also had no effect on either Kd or Bmax for calcium binding at any of the four sites whether measured in the presence of absence of NaCl or KCl. 6. It is concluded that previous reports of an effect of phosphorylation on calcium binding to a (Na+ + K+)-ATPase preparation may have been due to the presence of membrane material not directly associated with (Na+ + K+)-ATPase."}
{"id": "PMID:19067", "title": "3'-phosphoadenylylsulfate:galactosylceramide 3'-sulfotransferase. An optimized assay in homogenates of developing brain.", "content": "An optimized in vitro assay of 3'-phosphoadenylysulfate:galactosylceramide 3'-sulfotransferase (EC 2.8.2.11, galactosylceramide sulfotransferase, formerly known as galactocerebroside sulfotransferase) activity is presented, that can be used in crude homogenate of brain tissue of various developmental stages. The enzyme activity is determined by measuring the [35S]sulfatides formed by the enzymic transfer of [35S]sulfate from 3'-phosphoadenoside 5'-phospho [35S]sulfate to galactosylceramides. The sulfatide formation at 30 degrees C is linear up to 30 min and up to a protein concentration of 1 mg per 0.5 ml assay volume. The presence of 0.4% Triton X-100 and 50 micrometer exogenous bovine cerebrosides are optimal for enzyme activity. The pH optimum of the reaction is at pH 6.5 using 0.1 M imidazole buffer. The enzyme reaction is stimulated by NaCl, KCl, MgCl2, CaCl2, MnCl2, ATP and inhibited by ADP. The developmental enzyme activity pattern of mouse brain is the same, if derived from homogenates and microsomes, respectively, under our assay conditions.", "contents": "3'-phosphoadenylylsulfate:galactosylceramide 3'-sulfotransferase. An optimized assay in homogenates of developing brain. An optimized in vitro assay of 3'-phosphoadenylysulfate:galactosylceramide 3'-sulfotransferase (EC 2.8.2.11, galactosylceramide sulfotransferase, formerly known as galactocerebroside sulfotransferase) activity is presented, that can be used in crude homogenate of brain tissue of various developmental stages. The enzyme activity is determined by measuring the [35S]sulfatides formed by the enzymic transfer of [35S]sulfate from 3'-phosphoadenoside 5'-phospho [35S]sulfate to galactosylceramides. The sulfatide formation at 30 degrees C is linear up to 30 min and up to a protein concentration of 1 mg per 0.5 ml assay volume. The presence of 0.4% Triton X-100 and 50 micrometer exogenous bovine cerebrosides are optimal for enzyme activity. The pH optimum of the reaction is at pH 6.5 using 0.1 M imidazole buffer. The enzyme reaction is stimulated by NaCl, KCl, MgCl2, CaCl2, MnCl2, ATP and inhibited by ADP. The developmental enzyme activity pattern of mouse brain is the same, if derived from homogenates and microsomes, respectively, under our assay conditions."}
{"id": "PMID:19068", "title": "Spontaneous reactivation of acetylcholinesterase following organophosphate inhibition. I. An analysis of anomalous reactivation kinetics.", "content": "The first kinetic studies on the spontaneous reactivation of Sarin-inhibited acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) are reported. With increasing pH the extent of reactivation increases while the observed rate constant decreases. An analysis of the change in aging rate constant as a function of pH suggests that the aging of alkyl-alkoxy phosphonylated acetylcholinesterases is not solely acid catalyzed.", "contents": "Spontaneous reactivation of acetylcholinesterase following organophosphate inhibition. I. An analysis of anomalous reactivation kinetics. The first kinetic studies on the spontaneous reactivation of Sarin-inhibited acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) are reported. With increasing pH the extent of reactivation increases while the observed rate constant decreases. An analysis of the change in aging rate constant as a function of pH suggests that the aging of alkyl-alkoxy phosphonylated acetylcholinesterases is not solely acid catalyzed."}
{"id": "PMID:19069", "title": "Comparative studies on immobilization of human prostatic acid phosphatase.", "content": "Acid phosphatase (othophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2) from the human prostate was immobilized by its protein moiety on cyanogen bromide-activated Sepharose, by carbohydrate moiety on Concanavalin-A-Sepharose, and by Schiff base formation with partially oxidized carbohydrate groups on ethylenediamine-Sepharose. The highest retention of enzyme activity, 80%, was found for the noncovalent immobilization on Concanavalin-A-Sepharose. It was demonstrated that the optimal pH changes for the Concanavalin-A-Sepharose and CNBr-Sepharose-enzyme complexes are electrostratic in character. In all cases of immobilization the enzyme has higher thermostability than that for the native enzyme under the same conditions. The effects of the enzyme stabilization were interpreted in terms of the multipoint interaction between the enzyme molecule and the carrier.", "contents": "Comparative studies on immobilization of human prostatic acid phosphatase. Acid phosphatase (othophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2) from the human prostate was immobilized by its protein moiety on cyanogen bromide-activated Sepharose, by carbohydrate moiety on Concanavalin-A-Sepharose, and by Schiff base formation with partially oxidized carbohydrate groups on ethylenediamine-Sepharose. The highest retention of enzyme activity, 80%, was found for the noncovalent immobilization on Concanavalin-A-Sepharose. It was demonstrated that the optimal pH changes for the Concanavalin-A-Sepharose and CNBr-Sepharose-enzyme complexes are electrostratic in character. In all cases of immobilization the enzyme has higher thermostability than that for the native enzyme under the same conditions. The effects of the enzyme stabilization were interpreted in terms of the multipoint interaction between the enzyme molecule and the carrier."}
{"id": "PMID:19070", "title": "Harmaline interaction with sodium-binding sites in intestinal brush border sucrase.", "content": "The effect of harmaline on rabbit brush border sucrase has been studied at pH 6.8. An initial analysis in classical kinetic terms revealed harmaline to be a fully competitive inhibitor of the substrate, sucrose. In spite of this result however, the following hypothesis has been tested. Harmaline, which is positively charged in the physiological range of pH, might in fact compete, not directly with the substrate site, but rather with an allosterically-related sodium-binding site which has been postulated to be involved in the activation of sucrase by the alkali-metal ions (Mahmood and Alvarado, Arch. Biochem. Biophys. 168, 585, 1975). Because of its size, harmaline, when bound to the metal site, could at least partially overlap with the substrate site, thereby behaving as if it were an authentic fully competitive inhibitor of the substrate. This hypothesis appears to be confirmed by the fact that the alkali metals can completely reverse the inhibition caused by harmaline.", "contents": "Harmaline interaction with sodium-binding sites in intestinal brush border sucrase. The effect of harmaline on rabbit brush border sucrase has been studied at pH 6.8. An initial analysis in classical kinetic terms revealed harmaline to be a fully competitive inhibitor of the substrate, sucrose. In spite of this result however, the following hypothesis has been tested. Harmaline, which is positively charged in the physiological range of pH, might in fact compete, not directly with the substrate site, but rather with an allosterically-related sodium-binding site which has been postulated to be involved in the activation of sucrase by the alkali-metal ions (Mahmood and Alvarado, Arch. Biochem. Biophys. 168, 585, 1975). Because of its size, harmaline, when bound to the metal site, could at least partially overlap with the substrate site, thereby behaving as if it were an authentic fully competitive inhibitor of the substrate. This hypothesis appears to be confirmed by the fact that the alkali metals can completely reverse the inhibition caused by harmaline."}
{"id": "PMID:19071", "title": "Purification of angiotensin I-converting enzyme from human lung.", "content": "Angiotensin I-converting enzyme (peptidyl dipeptide hydrolase, EC 3.4.15.1) was solubilized from the membrane fraction of human lung using trypsin treatment and purfied using columns of DE 52-cellulose, hydroxyapatite and Sephadex G-200. The purified enzyme was shown to convert angiotensin I to angiotensin II and also to inactivate bradykinin. The specific activity of the enzyme was 9.5 units/mg protein for Hippuryl-His-Leu-OH and 0.665 mumol/min per mg protein for angiotensin I. The enzymic activity obtained after trypsin treatment (1 mg/200 mg protein) for 2 h could be divided into three components: (i) an enzyme of molecular weight 290 000 (peak I), (ii) an enzyme of molecular weight 180 000 (peak II) and (iii) an enzyme of molecular weight 98 000 (peak III), by columns of DE 52-cellulose and Sephadex G-200. Km values of peak I, II and III fraction for Hippuryl-His-Leu-OH were identical at 1.1 mM. pH optimum of the enzyme was 8.3 for Hippuryl-His-Leu-OH.", "contents": "Purification of angiotensin I-converting enzyme from human lung. Angiotensin I-converting enzyme (peptidyl dipeptide hydrolase, EC 3.4.15.1) was solubilized from the membrane fraction of human lung using trypsin treatment and purfied using columns of DE 52-cellulose, hydroxyapatite and Sephadex G-200. The purified enzyme was shown to convert angiotensin I to angiotensin II and also to inactivate bradykinin. The specific activity of the enzyme was 9.5 units/mg protein for Hippuryl-His-Leu-OH and 0.665 mumol/min per mg protein for angiotensin I. The enzymic activity obtained after trypsin treatment (1 mg/200 mg protein) for 2 h could be divided into three components: (i) an enzyme of molecular weight 290 000 (peak I), (ii) an enzyme of molecular weight 180 000 (peak II) and (iii) an enzyme of molecular weight 98 000 (peak III), by columns of DE 52-cellulose and Sephadex G-200. Km values of peak I, II and III fraction for Hippuryl-His-Leu-OH were identical at 1.1 mM. pH optimum of the enzyme was 8.3 for Hippuryl-His-Leu-OH."}
{"id": "PMID:19072", "title": "Isolation of buffalo muscle aldolase and comparison of its properties with those of rabbit muscle aldolase .", "content": "Fructose-1,6-bisphosphate aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phyosphate-lyase, EC 4.1.2.13) was isolated from buffalo muscle by fractionation with ammonium sulphate and subsequent purification by phosphocellulose column chromatography using a linear salt gradient. As judged by gel filtration and electrophoresis in polyacrylamide gel, the enzyme was homogeneous with respect to size and charge. The molecular weight and Stokes radius of the enzyme were determined from its elution profile on a calibrated Sephadex column and the respective values were 162000 and 4.55 nm. The diffusion coefficient and frictional ratio were computed to be 4.8-10(7) cm2-s-1 and 1.27, respectively. The molecular weight of the polypeptide chain as measured by aodium dodecyl sulphate polyacrylamide gel electrophoresis was 40750. This taken together with the native molecular weight suggested a four-subunit model for the protein. The  N- AND C-terminal residues of polypeptide chains were identified to be proline and tyrosine, respectively. At pH 8.0 the Michaelis-Menten constant and maximum attainable velocity were found to be 8.1 muM and 27 muM Fru-1,6-P2 split/min per mg, respectively. The buffalo muscle aldolase was found to be similar to rabbit muscle aldolase in physico-chemical properties. However, the two enzymes differ significantly in pH optimum; the p optima of the buffalo and rabbit enzymes were determined under identical conditions to be 8.0 and 8.6, respectively.", "contents": "Isolation of buffalo muscle aldolase and comparison of its properties with those of rabbit muscle aldolase . Fructose-1,6-bisphosphate aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phyosphate-lyase, EC 4.1.2.13) was isolated from buffalo muscle by fractionation with ammonium sulphate and subsequent purification by phosphocellulose column chromatography using a linear salt gradient. As judged by gel filtration and electrophoresis in polyacrylamide gel, the enzyme was homogeneous with respect to size and charge. The molecular weight and Stokes radius of the enzyme were determined from its elution profile on a calibrated Sephadex column and the respective values were 162000 and 4.55 nm. The diffusion coefficient and frictional ratio were computed to be 4.8-10(7) cm2-s-1 and 1.27, respectively. The molecular weight of the polypeptide chain as measured by aodium dodecyl sulphate polyacrylamide gel electrophoresis was 40750. This taken together with the native molecular weight suggested a four-subunit model for the protein. The  N- AND C-terminal residues of polypeptide chains were identified to be proline and tyrosine, respectively. At pH 8.0 the Michaelis-Menten constant and maximum attainable velocity were found to be 8.1 muM and 27 muM Fru-1,6-P2 split/min per mg, respectively. The buffalo muscle aldolase was found to be similar to rabbit muscle aldolase in physico-chemical properties. However, the two enzymes differ significantly in pH optimum; the p optima of the buffalo and rabbit enzymes were determined under identical conditions to be 8.0 and 8.6, respectively."}
{"id": "PMID:19074", "title": "Purification of methylmalonyl-CoA mutase from Propionibacterium shermanii using affinity chromatography.", "content": "A novel procedure for the purification of methylmalonyl-CA mutase from Propionibacterium shermanii has been described which employs affinity chromatography on a column of immobilized vitamin B-12 linked covalently to Sepharose. The method has the advantage of being simple and rapid, thus enabling the purification of the enzyme to near homogeneity with good yields.", "contents": "Purification of methylmalonyl-CoA mutase from Propionibacterium shermanii using affinity chromatography. A novel procedure for the purification of methylmalonyl-CA mutase from Propionibacterium shermanii has been described which employs affinity chromatography on a column of immobilized vitamin B-12 linked covalently to Sepharose. The method has the advantage of being simple and rapid, thus enabling the purification of the enzyme to near homogeneity with good yields."}
{"id": "PMID:19075", "title": "Enhanced heat, alkaline and tryptic stability of acetamidinated pig heart lactate dehydrogenase.", "content": "Modification of 17 from 24 lysine residues in pig heart lactate dehydrogenase (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27) with methyl aceimidate yields an enzyme derivative with enhanced stability toward meat and alkaline denaturation as well as tryptic digestion. The specific activity of the modified enzyme is only slightly reduced", "contents": "Enhanced heat, alkaline and tryptic stability of acetamidinated pig heart lactate dehydrogenase. Modification of 17 from 24 lysine residues in pig heart lactate dehydrogenase (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27) with methyl aceimidate yields an enzyme derivative with enhanced stability toward meat and alkaline denaturation as well as tryptic digestion. The specific activity of the modified enzyme is only slightly reduced"}
{"id": "PMID:19076", "title": "Solubilization and partial characterization of UDP-N-acetylgalactosamine: globoside alpha-N-acetylgalactosaminyltransferase from dog spleen microsomes.", "content": "UDP-N-acetylgalactosamine:globoside alpha-N-acetylgalactosaminyltransferase (EC 2.4.1.-) synthesizing Forssman hapten was solubilized from dog spleen microsomes by a combination of Triton X-100 treatment and sonication. The solubilized enzyme was partially purified by calcium phosphate gel, ammonium sulfate fractionation and then DEAE-cellulose column chromatography. The enzymatic activity of the purified preparation was stimulated by exogenously added phosphatidylserine, as found in the particulate enzyme. When the properties of the purified enzyme were examined in the presence of exogenous phosphatidylserine, the enzyme had an absolute requirement for Mn2+; this was not substituted by Ca2+ or Mg2+. Apparent Km values for UDP-N-acetylgalactosamine and globoside were 1-10(-5) and 5-10(-4) M, respectively. It had a pH optimum of 6.55 regardless of the presence or absence of exogenous lipids. Since the partially purified enzyme was completely free of uridine diphosphatase which was found in the particulate preparaton, the effect of UDP on the transferase activity could be studied. Thus, UDP inhibited 85% of the activity at a concentration of 1.5 mM. p-Cholormercuribenzoate inhibited over 90% of the activity at 2 mM, indicating the transferase to be SH-enzyme.", "contents": "Solubilization and partial characterization of UDP-N-acetylgalactosamine: globoside alpha-N-acetylgalactosaminyltransferase from dog spleen microsomes. UDP-N-acetylgalactosamine:globoside alpha-N-acetylgalactosaminyltransferase (EC 2.4.1.-) synthesizing Forssman hapten was solubilized from dog spleen microsomes by a combination of Triton X-100 treatment and sonication. The solubilized enzyme was partially purified by calcium phosphate gel, ammonium sulfate fractionation and then DEAE-cellulose column chromatography. The enzymatic activity of the purified preparation was stimulated by exogenously added phosphatidylserine, as found in the particulate enzyme. When the properties of the purified enzyme were examined in the presence of exogenous phosphatidylserine, the enzyme had an absolute requirement for Mn2+; this was not substituted by Ca2+ or Mg2+. Apparent Km values for UDP-N-acetylgalactosamine and globoside were 1-10(-5) and 5-10(-4) M, respectively. It had a pH optimum of 6.55 regardless of the presence or absence of exogenous lipids. Since the partially purified enzyme was completely free of uridine diphosphatase which was found in the particulate preparaton, the effect of UDP on the transferase activity could be studied. Thus, UDP inhibited 85% of the activity at a concentration of 1.5 mM. p-Cholormercuribenzoate inhibited over 90% of the activity at 2 mM, indicating the transferase to be SH-enzyme."}
{"id": "PMID:19077", "title": "A conformational change in phosphoglycerate dehydrogenase induced by a shift in pH.", "content": "The fluorescence of NADH bound to phosphoglycerate dehydrogenase (3-phosphoglycerate: NAD+ oxidoreductase, EC 1.1.1.95) decreased by 42% between pH 8.5 and 7.0 Serine, an allosteric inhibitor, quenched the fluorescence of enzyme-bound NADH by 29% at pH 8.5, but not at all at pH 7.0. The kinetics of the fluorescence change which occurred when the pH of an enzyme-NADH solution was rapidly shifted from 8.5 to 7.0 was measured using stopped-flow fluorimetry. The kinetics were first order, with a rate constant of 2.83 s-1. This rate constant was similar in magnitude to the rate constants for fluorescence quenching at pH 8.5 by saturating concentrations of serine and glycine, another allosteric inhibitor (Dubrow, R. and Pizer, L.I. (1977) J. Biol. Chem. 252, 1527-1538). These results indicate that the conformation of phosphoglycerate dehydrogenase at pH 7.0 is similar to, but not identical with, the serine-induced conformation at pH 8.5.", "contents": "A conformational change in phosphoglycerate dehydrogenase induced by a shift in pH. The fluorescence of NADH bound to phosphoglycerate dehydrogenase (3-phosphoglycerate: NAD+ oxidoreductase, EC 1.1.1.95) decreased by 42% between pH 8.5 and 7.0 Serine, an allosteric inhibitor, quenched the fluorescence of enzyme-bound NADH by 29% at pH 8.5, but not at all at pH 7.0. The kinetics of the fluorescence change which occurred when the pH of an enzyme-NADH solution was rapidly shifted from 8.5 to 7.0 was measured using stopped-flow fluorimetry. The kinetics were first order, with a rate constant of 2.83 s-1. This rate constant was similar in magnitude to the rate constants for fluorescence quenching at pH 8.5 by saturating concentrations of serine and glycine, another allosteric inhibitor (Dubrow, R. and Pizer, L.I. (1977) J. Biol. Chem. 252, 1527-1538). These results indicate that the conformation of phosphoglycerate dehydrogenase at pH 7.0 is similar to, but not identical with, the serine-induced conformation at pH 8.5."}
{"id": "PMID:19080", "title": "Ganglioside biosynthesis. Characterization of CMP-N-acetylneuraminic acid : lactosylceramide sialyltransferase in Golgi apparatus from rat liver.", "content": "An enzyme that transfers sialic acid from GMP-sialic acid to lactosylceramide was concentrated 40-50 times in Golgi apparatus from rat liver relative to total homogenates. This enzyme required detergents as dispersing agents. Of the numerous detergents tested, the combination Tween 80-Triton CF-54 (1 : 2, w/w) was the most effective in stimulating the reaction. Two apparent pH optima, at 6.35 and 5.5, were observed. The enzyme showed no requirement for a divalent cation. The Km values calculated for CMP-N-acetylneuraminic acid and lactosylceramide were 2.7 - 10(-3) and 1.3 - 10(-4) M, respectively. The enzyme could not be dissociated from Golgi apparatus fractions by treatment with ultrasound, indicating that it is tightly associated with the membrane. The newly synthesized GM3, the product of the reaction, was incorporated into or became tightly associated with the membranes of the Golgi apparatus.", "contents": "Ganglioside biosynthesis. Characterization of CMP-N-acetylneuraminic acid : lactosylceramide sialyltransferase in Golgi apparatus from rat liver. An enzyme that transfers sialic acid from GMP-sialic acid to lactosylceramide was concentrated 40-50 times in Golgi apparatus from rat liver relative to total homogenates. This enzyme required detergents as dispersing agents. Of the numerous detergents tested, the combination Tween 80-Triton CF-54 (1 : 2, w/w) was the most effective in stimulating the reaction. Two apparent pH optima, at 6.35 and 5.5, were observed. The enzyme showed no requirement for a divalent cation. The Km values calculated for CMP-N-acetylneuraminic acid and lactosylceramide were 2.7 - 10(-3) and 1.3 - 10(-4) M, respectively. The enzyme could not be dissociated from Golgi apparatus fractions by treatment with ultrasound, indicating that it is tightly associated with the membrane. The newly synthesized GM3, the product of the reaction, was incorporated into or became tightly associated with the membranes of the Golgi apparatus."}
{"id": "PMID:19081", "title": "Thermodynamics of lipid protein associations. Thermodynamics of helix formation in the association of high density apolipoprotein A-I (apoA-I) to dimyristoyl phosphatidylcholine.", "content": "The structure and phospholipid-binding properties of human plasma high density apolipoprotein A-I (apoA-I) has been studied at pH 7.4 and 3.1 by microcalorimetry, circular dichroism and density gradient ultracentrifugation. At pH values of 7.4 and 3.1, apoA-I binds to dimyristoyl phosphatidylcholine (DMPC) to form complexes of similar composition (molar ratio of DMPC/apoA-I of 100) and helical content (67%). At pH 7.4, the lipid-protein association is accompanied by an increase in helical content from 58 to 67% and an exothermic enthalpy of binding (deltaHB) of -90 kcal/mol apoA-I. At pH 3.1, the helical content of apoA-I is increased from 48 to 67% on binding to DMPC and the enthalpy of binding was -170 kcal/mol. We suggest that the difference in the enthalpies of binding (-80 kcal/mol) at pH 3.1 compared to 7.4 is due to the greater coil leads to helix transition at the lower pH.", "contents": "Thermodynamics of lipid protein associations. Thermodynamics of helix formation in the association of high density apolipoprotein A-I (apoA-I) to dimyristoyl phosphatidylcholine. The structure and phospholipid-binding properties of human plasma high density apolipoprotein A-I (apoA-I) has been studied at pH 7.4 and 3.1 by microcalorimetry, circular dichroism and density gradient ultracentrifugation. At pH values of 7.4 and 3.1, apoA-I binds to dimyristoyl phosphatidylcholine (DMPC) to form complexes of similar composition (molar ratio of DMPC/apoA-I of 100) and helical content (67%). At pH 7.4, the lipid-protein association is accompanied by an increase in helical content from 58 to 67% and an exothermic enthalpy of binding (deltaHB) of -90 kcal/mol apoA-I. At pH 3.1, the helical content of apoA-I is increased from 48 to 67% on binding to DMPC and the enthalpy of binding was -170 kcal/mol. We suggest that the difference in the enthalpies of binding (-80 kcal/mol) at pH 3.1 compared to 7.4 is due to the greater coil leads to helix transition at the lower pH."}
{"id": "PMID:19082", "title": "Characterization and partial purification of acid lipase from human leucocytes.", "content": "Hydrolysis of glycerol trioleate by human leucocytes was characterized and the enzymes responsible for this activity were obtained in a purified form by means of gel chromatography on Sephadex G-100 as well as by zonal ultracentrifugation followed by gel chromatography. The activity is localized in the granule fraction of leucocytes (15 000 X g, 20 min) and shows a sharp pH optimum at pH 5.25. As judged from the elution profile obtained by gel chromatography, two proteins are likely to contribute to the hydrolysis of glycerol trioleate. The approximate molecular weights of the two enzymes are 74 100 and 60 300, respectively. The activity is reduced in the presence of NaCl, KCl, CaCl2 as well as of p-hydroxymercuribenzoate. The enzymes are stable at -25 degrees C but loose about 50% of their activity within 48 h at 4 degrees C.", "contents": "Characterization and partial purification of acid lipase from human leucocytes. Hydrolysis of glycerol trioleate by human leucocytes was characterized and the enzymes responsible for this activity were obtained in a purified form by means of gel chromatography on Sephadex G-100 as well as by zonal ultracentrifugation followed by gel chromatography. The activity is localized in the granule fraction of leucocytes (15 000 X g, 20 min) and shows a sharp pH optimum at pH 5.25. As judged from the elution profile obtained by gel chromatography, two proteins are likely to contribute to the hydrolysis of glycerol trioleate. The approximate molecular weights of the two enzymes are 74 100 and 60 300, respectively. The activity is reduced in the presence of NaCl, KCl, CaCl2 as well as of p-hydroxymercuribenzoate. The enzymes are stable at -25 degrees C but loose about 50% of their activity within 48 h at 4 degrees C."}
{"id": "PMID:19083", "title": "The isolation and characterization of sphingomyelinase from human placental tissue.", "content": "Human placental sphingomyelinase activity was eluted as a single symmetrical peak from Sephadex G-200 with a molecular weight of 290000; however, the enzyme behaved heterogeneously on ion exchange chromatography. A specific species of sphingomyelinase was purified approx. 10 000-fold to a constant specific activity of 274 000 nanomol of sphingomyelin hydrolyzed per mg protein per h. When the purified enzyme was examined on sodium dodecyl sulfate disc gel electrophoresis, two distinct protein bands in approximately equal proportions with molecular weights of 36 800 and 28 300 were found. The specificity of the enzyme is directed towards both the hydrophilic phosphocholine and the hydrophobic ceramide moieties of sphingomyelin. Possible interrelationships between the heterogenous forms of placental sphingomyelinases are discussed.", "contents": "The isolation and characterization of sphingomyelinase from human placental tissue. Human placental sphingomyelinase activity was eluted as a single symmetrical peak from Sephadex G-200 with a molecular weight of 290000; however, the enzyme behaved heterogeneously on ion exchange chromatography. A specific species of sphingomyelinase was purified approx. 10 000-fold to a constant specific activity of 274 000 nanomol of sphingomyelin hydrolyzed per mg protein per h. When the purified enzyme was examined on sodium dodecyl sulfate disc gel electrophoresis, two distinct protein bands in approximately equal proportions with molecular weights of 36 800 and 28 300 were found. The specificity of the enzyme is directed towards both the hydrophilic phosphocholine and the hydrophobic ceramide moieties of sphingomyelin. Possible interrelationships between the heterogenous forms of placental sphingomyelinases are discussed."}
{"id": "PMID:19084", "title": "Reaction of selenium with immunoglobulin molecules.", "content": "Radioactive selenite reacts with purified human and goat immunoglobulins at acidic and neutral pH. The antigenic properties of the immunoglobulins are retained during the selenium labelling as shown by immunoelectrophoresis and autoradiography. Pepsin digests of 75Se-labelled IgG possess 75Se both in the (Fab')2 fraction and in the low molecular weight peptides derived from the Fc domains. Alpha-1-acid glycoprotein, ribonuclease, and lysozyme are also labelled by this procedure. Enhancement of 75Se incorporation by urea, guanidinium chloride, mercaptoethanol, sodium sulfite and carrier selenite is interpreted as an effect of destabilization of IgG disulfide bonds. Up to 1.4 g atoms Se per mol IgG have been incorporated. We assume that selenite is cleaving disulfides by a process akin to sulfitolysis. The lability of the isolated 75Se-labelled IgG to high concentrations of mercaptans and sulfite is consistent with this idea. These 75Se-labelled proteins may be useful in structure studies and radioimmunoassay.", "contents": "Reaction of selenium with immunoglobulin molecules. Radioactive selenite reacts with purified human and goat immunoglobulins at acidic and neutral pH. The antigenic properties of the immunoglobulins are retained during the selenium labelling as shown by immunoelectrophoresis and autoradiography. Pepsin digests of 75Se-labelled IgG possess 75Se both in the (Fab')2 fraction and in the low molecular weight peptides derived from the Fc domains. Alpha-1-acid glycoprotein, ribonuclease, and lysozyme are also labelled by this procedure. Enhancement of 75Se incorporation by urea, guanidinium chloride, mercaptoethanol, sodium sulfite and carrier selenite is interpreted as an effect of destabilization of IgG disulfide bonds. Up to 1.4 g atoms Se per mol IgG have been incorporated. We assume that selenite is cleaving disulfides by a process akin to sulfitolysis. The lability of the isolated 75Se-labelled IgG to high concentrations of mercaptans and sulfite is consistent with this idea. These 75Se-labelled proteins may be useful in structure studies and radioimmunoassay."}
{"id": "PMID:19085", "title": "Magnetic circular dichroism studies on acid and alkaline forms of horseradish peroxidase.", "content": "The heme vicinities of the acid and alkaline forms of native (Fd(III)) horseradish peroxidase were investigated in terms of the magnetic circular dichroism (MCD) spectroscopy. The MCD spectrum of the acid form of native horseradish peroxidase was characteristic of a ferric high spin heme group. The resemblance in the MCD spectrum between the acid form and acetato-iron (III)protoporphyrin IX dimethyl ester suggests that the heme iron of the acid form has the electronic structure similar to that in a pentocoordinated heme complex. The MCD spectra of native horseradish peroxidase did not shown any substantial pH dependence in the pH range from 5.20 to 9.00. The MCD spectral change indicated the pK value for the equilibrium between the acid and alkaline forms to be 11.0 which agrees with the results from other methods. The alkaline form of native horseradish peroxidase at pH 12.01 exhibited the MCD spectrum of a low spin complex. The near infrared MCD spectrum suggests that the alkaline form of native horseradish peroxidase has a 6th ligand somehow different from a normal nitrogen ligand such as histidine or lysine. It implicates that the alkaline form has an overall ligand field strength of between the low spin component of metmyoglobin hydroxide and metmyoglobin azide.", "contents": "Magnetic circular dichroism studies on acid and alkaline forms of horseradish peroxidase. The heme vicinities of the acid and alkaline forms of native (Fd(III)) horseradish peroxidase were investigated in terms of the magnetic circular dichroism (MCD) spectroscopy. The MCD spectrum of the acid form of native horseradish peroxidase was characteristic of a ferric high spin heme group. The resemblance in the MCD spectrum between the acid form and acetato-iron (III)protoporphyrin IX dimethyl ester suggests that the heme iron of the acid form has the electronic structure similar to that in a pentocoordinated heme complex. The MCD spectra of native horseradish peroxidase did not shown any substantial pH dependence in the pH range from 5.20 to 9.00. The MCD spectral change indicated the pK value for the equilibrium between the acid and alkaline forms to be 11.0 which agrees with the results from other methods. The alkaline form of native horseradish peroxidase at pH 12.01 exhibited the MCD spectrum of a low spin complex. The near infrared MCD spectrum suggests that the alkaline form of native horseradish peroxidase has a 6th ligand somehow different from a normal nitrogen ligand such as histidine or lysine. It implicates that the alkaline form has an overall ligand field strength of between the low spin component of metmyoglobin hydroxide and metmyoglobin azide."}
{"id": "PMID:19086", "title": "Circular dichroism and conformation of human alpha1-antitrypsin.", "content": "The solution conformation of alpha 1-antitrypsin from human blood plasma was studied by the circular dichroism (CD) probe. The CD spectra revealed in this glycoprotein approximately 16-20% of alpha-helix, the rest of the main polypeptide chain possessing the pleated sheet (beta) and the aperiodic structures. The conformation was stable between pH 4.7 and 8.8. Reversible change in conformation was observed at pH 10.3, and more dratic denaturation occurred at pH 11.6. The environment of the side chain chromophores was strongly affected by acid at pH 2.5, whereas the main chain conformation was changed slightly. A drastic change in the CD spectra, indicating denaturation, was observed in 3.5 M guanidine hydrochloride. Sodium dodecyl sulfate was effective in disorganizing the tertiary structure and in enhancing the helix content. The phenylalanine band fine structure was observed in the native protein and also after denaturation with acid, guanidine hydrochloride and sodium dodecyl sulfate.", "contents": "Circular dichroism and conformation of human alpha1-antitrypsin. The solution conformation of alpha 1-antitrypsin from human blood plasma was studied by the circular dichroism (CD) probe. The CD spectra revealed in this glycoprotein approximately 16-20% of alpha-helix, the rest of the main polypeptide chain possessing the pleated sheet (beta) and the aperiodic structures. The conformation was stable between pH 4.7 and 8.8. Reversible change in conformation was observed at pH 10.3, and more dratic denaturation occurred at pH 11.6. The environment of the side chain chromophores was strongly affected by acid at pH 2.5, whereas the main chain conformation was changed slightly. A drastic change in the CD spectra, indicating denaturation, was observed in 3.5 M guanidine hydrochloride. Sodium dodecyl sulfate was effective in disorganizing the tertiary structure and in enhancing the helix content. The phenylalanine band fine structure was observed in the native protein and also after denaturation with acid, guanidine hydrochloride and sodium dodecyl sulfate."}
{"id": "PMID:19087", "title": "Iron exchange between transferrin molecules mediated by phosphate compounds and other cell metabolites.", "content": "The ability of a large number of cellular metabolites to release iron from transferrin was investigated by measuring the rate at which they could mediate iron exchange between two types of transferrin. Rabbit transferrin labelled with 59Fe was incubated with human apotransferrin in the presence of the metabolites. After varying periods of incubation the human transferrin was separated from the rabbit transferrin by immunoprecipitation. GTP, 2,3-diphosphoglycerate, ATP, ADP and citrate produced the most rapid exchange of iron between the two types of transferrin, but many other compounds showed some degree of activity. Iron exchange mediated by the organic phosphates had the characteristics of a single first-order reaction and was sensitive to changes of incubation temperature and pH. The activation energy for the exchange reaction was approx. 13 kcal/mol. The rate of iron exchange from the oxalate - iron - transferrin complex was much lower than from bicarbonate - iron - transferrin. It is concluded that several organic phosphates have the capacity of releasing iron from transferrin. These compounds may represent the means by which the iron is released during the process of cellular uptake.", "contents": "Iron exchange between transferrin molecules mediated by phosphate compounds and other cell metabolites. The ability of a large number of cellular metabolites to release iron from transferrin was investigated by measuring the rate at which they could mediate iron exchange between two types of transferrin. Rabbit transferrin labelled with 59Fe was incubated with human apotransferrin in the presence of the metabolites. After varying periods of incubation the human transferrin was separated from the rabbit transferrin by immunoprecipitation. GTP, 2,3-diphosphoglycerate, ATP, ADP and citrate produced the most rapid exchange of iron between the two types of transferrin, but many other compounds showed some degree of activity. Iron exchange mediated by the organic phosphates had the characteristics of a single first-order reaction and was sensitive to changes of incubation temperature and pH. The activation energy for the exchange reaction was approx. 13 kcal/mol. The rate of iron exchange from the oxalate - iron - transferrin complex was much lower than from bicarbonate - iron - transferrin. It is concluded that several organic phosphates have the capacity of releasing iron from transferrin. These compounds may represent the means by which the iron is released during the process of cellular uptake."}
{"id": "PMID:19088", "title": "Contribution of pH-sensitive metabolic processes to pH homeostasis in isolated rat kidney tubules.", "content": "The metabolism of isolated rat kidney tubules suspended in calcium-free physiological saline buffered with phosphate was found to be sensitive to changes in the pH of the suspending medium. Lowering the pH from 7.8 to 6.4 brought about increases in the rates of oxidation of added succinate, glutamate or glutamine as well as in the production of glucose from lactate, glutamine, succinate and fructose. The cellular ATP level was also higher in tubules incubated at pH 6.4 In contrast, the utilization of added glucose was greater at pH 7.8 than at pH 6.4, a substantial amount of lactate being produced at the higher pH. When glucose and either lactate or glutamine were provided as co-substrates glucose was the preferred fuel at pH 7.8 but the alternative substrate was the more readily utilized at pH 6.4. As a consequence of the metabolic  activities of the tubules the pH of the suspending medium changed, utilization of lactate, glutamate or glutamine causing a rise in pH while conversion of glucose to lactate caused a fall in pH. In cases where two substrates were metabolized concurrently over a period of 3 h the extracellular pH tended towards a plateau level of approximately pH 7.4. It is proposed that pH-sensitive metabolism in isolated kidney tubules contributes to pH homeostasis in the cellular environment.", "contents": "Contribution of pH-sensitive metabolic processes to pH homeostasis in isolated rat kidney tubules. The metabolism of isolated rat kidney tubules suspended in calcium-free physiological saline buffered with phosphate was found to be sensitive to changes in the pH of the suspending medium. Lowering the pH from 7.8 to 6.4 brought about increases in the rates of oxidation of added succinate, glutamate or glutamine as well as in the production of glucose from lactate, glutamine, succinate and fructose. The cellular ATP level was also higher in tubules incubated at pH 6.4 In contrast, the utilization of added glucose was greater at pH 7.8 than at pH 6.4, a substantial amount of lactate being produced at the higher pH. When glucose and either lactate or glutamine were provided as co-substrates glucose was the preferred fuel at pH 7.8 but the alternative substrate was the more readily utilized at pH 6.4. As a consequence of the metabolic  activities of the tubules the pH of the suspending medium changed, utilization of lactate, glutamate or glutamine causing a rise in pH while conversion of glucose to lactate caused a fall in pH. In cases where two substrates were metabolized concurrently over a period of 3 h the extracellular pH tended towards a plateau level of approximately pH 7.4. It is proposed that pH-sensitive metabolism in isolated kidney tubules contributes to pH homeostasis in the cellular environment."}
{"id": "PMID:19091", "title": "Purification and properties of rat brain succinic semialdehyde dehydrogenase.", "content": "Succinic semialdehyde dehydrogenase from rat brain has been purified to electrophoretic homogeneity. It has a molecular weight of about 140, 000 and is composed of two apparently identical subunits. The reaction catalized by the pure protein is entirely dependent on endogenous --SH groups. The Kim (limits) for NAD and succinic semialdehyde are 2 X 10(-5) M and 1 X 10(-4) M respectively at the optimum pH of 8.6. Inhibition studies show that the reaction mechanism is a compulsory ordered on where NAD binds first followed by succinic semialdehyde.", "contents": "Purification and properties of rat brain succinic semialdehyde dehydrogenase. Succinic semialdehyde dehydrogenase from rat brain has been purified to electrophoretic homogeneity. It has a molecular weight of about 140, 000 and is composed of two apparently identical subunits. The reaction catalized by the pure protein is entirely dependent on endogenous --SH groups. The Kim (limits) for NAD and succinic semialdehyde are 2 X 10(-5) M and 1 X 10(-4) M respectively at the optimum pH of 8.6. Inhibition studies show that the reaction mechanism is a compulsory ordered on where NAD binds first followed by succinic semialdehyde."}
{"id": "PMID:19089", "title": "[Role of phycobilin pigments in photosynthesis].", "content": "Experimental data on possible role of phicobilliprotein (PhBP) in photosynthesis are analysed. It is concluded that the widely spread notion about PhBP only as the light-gathering pigments which transfer the energy to chlorophyll, turned to be insufficiently substantiated experimentally until recently. At the same time the discovered ability of PhBP for reversible redox transformations together with the new data on the nature of fluorescence of blue-green algae and PhBP localization in the cell allowed a suggestion that PhBP can independently of chlorophyll or together with it directly participate in photochemical reactions of photosynthesis. A suggestion is advanced concerning possible existence of the reaction centres of PhBP in phicobillisomes.", "contents": "[Role of phycobilin pigments in photosynthesis]. Experimental data on possible role of phicobilliprotein (PhBP) in photosynthesis are analysed. It is concluded that the widely spread notion about PhBP only as the light-gathering pigments which transfer the energy to chlorophyll, turned to be insufficiently substantiated experimentally until recently. At the same time the discovered ability of PhBP for reversible redox transformations together with the new data on the nature of fluorescence of blue-green algae and PhBP localization in the cell allowed a suggestion that PhBP can independently of chlorophyll or together with it directly participate in photochemical reactions of photosynthesis. A suggestion is advanced concerning possible existence of the reaction centres of PhBP in phicobillisomes."}
{"id": "PMID:19092", "title": "Presence of a third sucrose hydrolyzing enzyme in Bacillus subtilis: constitutive levanase synthesis by mutants of Bacillus subtilis Marburg 168.", "content": "A beta-D-fructofuranosidase -- called levanase -- capable of the hydrolysis of sucrose, inulin and levans has been identified in Bacillus subtilis Marburg. This enzyme can not be detected in strain 168. However, sacL mutations -- mapped on the chromosome of strain 168 between the pheA and aroD reference markers -- lead to constitutive levanase synthesis. This synthesis is repressed by carbon sources such as glucose, glycerol or sucrose.", "contents": "Presence of a third sucrose hydrolyzing enzyme in Bacillus subtilis: constitutive levanase synthesis by mutants of Bacillus subtilis Marburg 168. A beta-D-fructofuranosidase -- called levanase -- capable of the hydrolysis of sucrose, inulin and levans has been identified in Bacillus subtilis Marburg. This enzyme can not be detected in strain 168. However, sacL mutations -- mapped on the chromosome of strain 168 between the pheA and aroD reference markers -- lead to constitutive levanase synthesis. This synthesis is repressed by carbon sources such as glucose, glycerol or sucrose."}
{"id": "PMID:19093", "title": "[Genetic independence of two forms of carbonic anhydrase from bovine erythrocytes].", "content": "The two major forms of bovine erythrocyte carbonic anhydrase have been designated as CI and CII because their high activity of the C type. Separation of both forms and isolation of CI from the ethanol chloroform extract of the hemolysate were obtained by either column chromatography on DEAE-cellulose DE 23 or on DEAE-sephadex A-50. But pure preparations of the CII form were only obtained from DEAE-sephadex A-50 which separated CII from a minor component CIv1. Comparative studies of the CI and CII forms and of the minor component CIv1 strongly suggest that CIv1 is a conformational variant of CI and CII are genetic variants differing at least in their primary structure by one Arg yields Gln substitution 56 residues from the N-acetylated terminus. Based on the large variability of the proportion of the two isozymes in heterozygous individuals, the modality of the inheritance of these enzymes is discussed.", "contents": "[Genetic independence of two forms of carbonic anhydrase from bovine erythrocytes]. The two major forms of bovine erythrocyte carbonic anhydrase have been designated as CI and CII because their high activity of the C type. Separation of both forms and isolation of CI from the ethanol chloroform extract of the hemolysate were obtained by either column chromatography on DEAE-cellulose DE 23 or on DEAE-sephadex A-50. But pure preparations of the CII form were only obtained from DEAE-sephadex A-50 which separated CII from a minor component CIv1. Comparative studies of the CI and CII forms and of the minor component CIv1 strongly suggest that CIv1 is a conformational variant of CI and CII are genetic variants differing at least in their primary structure by one Arg yields Gln substitution 56 residues from the N-acetylated terminus. Based on the large variability of the proportion of the two isozymes in heterozygous individuals, the modality of the inheritance of these enzymes is discussed."}
{"id": "PMID:19095", "title": "A fine-structural study of embryonic and larval development in the gymnoblastic hydroid Pennaria tiarella.", "content": "1. The pregastrulation blastomers contain electron-dense granules which become localized after gastrulation in the apices of the developing epithelio-muscle cells and persist throughout larval development. The cytoplasm of the blastomeres is organized into anucleate, membrane-delimited lobules. The lobules, which persist until six hours of development, come to contain a single, peripherally located cisterna of granular endoplasmic reticulum. Microvilli are present at the earliest stages examined and persist throughout development. Cilia are first detected at four hours. 2. Gastrulation, marked by the appearance of the mesoglea, occurs between six and eight hours of development. Basal foot processes of epithelio-muscle cells are detected by eight hours, but myonemes cannot be detected until later in development. 3. Immediately following gastrulation, mucous cells begin their differentiation from dividing cells located near the apex of the ectoderm. During their differentiation, the cells elongate toward the mesoglea. 4. By 16 hours post-fertilization, a third cell type can be detected in the ectoderm. The cell, which contains no granules, has an unusual cytoplasmic organization in which fused membranes divide the cytoplasm into parallel compartments containing a single cisterna of granular endoplasmic reticulum. 5. The findings of the present study are correlated with those of previous studies of development in Pennaria and other hydroids. The possible functional roles of the Type I granules, the cytoplasmic lobules, and the nongranular cell are discussed.", "contents": "A fine-structural study of embryonic and larval development in the gymnoblastic hydroid Pennaria tiarella. 1. The pregastrulation blastomers contain electron-dense granules which become localized after gastrulation in the apices of the developing epithelio-muscle cells and persist throughout larval development. The cytoplasm of the blastomeres is organized into anucleate, membrane-delimited lobules. The lobules, which persist until six hours of development, come to contain a single, peripherally located cisterna of granular endoplasmic reticulum. Microvilli are present at the earliest stages examined and persist throughout development. Cilia are first detected at four hours. 2. Gastrulation, marked by the appearance of the mesoglea, occurs between six and eight hours of development. Basal foot processes of epithelio-muscle cells are detected by eight hours, but myonemes cannot be detected until later in development. 3. Immediately following gastrulation, mucous cells begin their differentiation from dividing cells located near the apex of the ectoderm. During their differentiation, the cells elongate toward the mesoglea. 4. By 16 hours post-fertilization, a third cell type can be detected in the ectoderm. The cell, which contains no granules, has an unusual cytoplasmic organization in which fused membranes divide the cytoplasm into parallel compartments containing a single cisterna of granular endoplasmic reticulum. 5. The findings of the present study are correlated with those of previous studies of development in Pennaria and other hydroids. The possible functional roles of the Type I granules, the cytoplasmic lobules, and the nongranular cell are discussed."}
{"id": "PMID:19096", "title": "[Identification and properties of 2 forms of plant phospholipase D].", "content": "Effect of different factors (pH, temperature etc.) on the activity of phospholipase D is studied. It is found that plant phospholipase D has two forms: thermolabile (D1) and thermostable (Ds). Both forms are shown to differ in some characteristics (pH optimum, temperature optimum, calcium ions activation, activator effect, kinetic parameters, thermostavility). The contradictive literature data on phospholipase D properties are suggested to be due to the existence of two enzyme forms.", "contents": "[Identification and properties of 2 forms of plant phospholipase D]. Effect of different factors (pH, temperature etc.) on the activity of phospholipase D is studied. It is found that plant phospholipase D has two forms: thermolabile (D1) and thermostable (Ds). Both forms are shown to differ in some characteristics (pH optimum, temperature optimum, calcium ions activation, activator effect, kinetic parameters, thermostavility). The contradictive literature data on phospholipase D properties are suggested to be due to the existence of two enzyme forms."}
{"id": "PMID:19097", "title": "[Isolation and properties of leucine aminopeptidase from Aspergillus oryzae].", "content": "Homogenious leucine aminopeptidase is purified from \"oryzine\"--mixture of enzymes produced by surface culture of Asperigillus oryzae using treatment with activated characoal, followed by DEAE-cellulose and hydroxylapatite chromatographies, Biogel P-100 gel-filtration and polyacrylamide-gel electrophoresis. The enzyme has pH optimum 9.0 and the molecular weight 37500 as estimated by gil-filtration through Sephadex G-100 (superfine) and SDS-polyacrylamide gel electrophoresis. Leucine aminopeptidase from Asp. oryzae has a broad substrate specificity, therefore, cleaving with the highest rate the peptides carrying N-terminal leucine. The enzyme is completely inhibited with EDTA and beta-mercaptoethanol, and it is a metalloenzyme.", "contents": "[Isolation and properties of leucine aminopeptidase from Aspergillus oryzae]. Homogenious leucine aminopeptidase is purified from \"oryzine\"--mixture of enzymes produced by surface culture of Asperigillus oryzae using treatment with activated characoal, followed by DEAE-cellulose and hydroxylapatite chromatographies, Biogel P-100 gel-filtration and polyacrylamide-gel electrophoresis. The enzyme has pH optimum 9.0 and the molecular weight 37500 as estimated by gil-filtration through Sephadex G-100 (superfine) and SDS-polyacrylamide gel electrophoresis. Leucine aminopeptidase from Asp. oryzae has a broad substrate specificity, therefore, cleaving with the highest rate the peptides carrying N-terminal leucine. The enzyme is completely inhibited with EDTA and beta-mercaptoethanol, and it is a metalloenzyme."}
{"id": "PMID:19098", "title": "[Malic acid induction of decarboxylating NADP-malate dehydrogenase synthesis in C3-plant leaves].", "content": "The activity of decarboxylating NADP-malatedehydrogenase (E. C. 1.1.1.40) in green ethiolated pea and barley leaves and in green leaves of a pea mutant lacking photosystem II is found to be 3-fold increased after the injection of malic acid into cut plants. Protein synthesis inhibitors depressed malic acid-induced increase of the activity of \"malic\"-enzyme, the effect of chloramphenicol being more pronounced in ethiolated green leaves, and that of cycloheximide--in leaves of a mutant with formed photosynthetic apparatus. Possible dependence of malate-induced biosynthesis of \"malic\"-enzyme on the degree of NADP reduction in chloroplasts is discussed.", "contents": "[Malic acid induction of decarboxylating NADP-malate dehydrogenase synthesis in C3-plant leaves]. The activity of decarboxylating NADP-malatedehydrogenase (E. C. 1.1.1.40) in green ethiolated pea and barley leaves and in green leaves of a pea mutant lacking photosystem II is found to be 3-fold increased after the injection of malic acid into cut plants. Protein synthesis inhibitors depressed malic acid-induced increase of the activity of \"malic\"-enzyme, the effect of chloramphenicol being more pronounced in ethiolated green leaves, and that of cycloheximide--in leaves of a mutant with formed photosynthetic apparatus. Possible dependence of malate-induced biosynthesis of \"malic\"-enzyme on the degree of NADP reduction in chloroplasts is discussed."}
{"id": "PMID:19099", "title": "[Characteristics of acid ribonuclease from rat thymus chromatin].", "content": "Acid ribonuclease, free of nucleases and phosphatases, is isolated from rat thymus chromatin. The pH optimum of the enzyme is 5.0-5.5, optimal concentrations of Na+ and K+ ions are 0.05-0.15 M and 0.05 M respectively, Mg2+ inhibits the enzyme activity. The enzyme hydrolyses poly U, poly AU, cytoplasmic and nuclear RNAs, but does not attack poly A, polyG, polyC, poly A:poly U, native and denatured DNA'S. The enzyme is 3'-endonuclease, it splits the bond between the 5'-carbon atom of adenosine, guanosine and uridine and 3'-phosphate of uridilic residue. Middle length of oligonucleotides after the hydrolysis of cytoplasmic RNA comprises 10 nucleotides. Possible role of the enzyme in the processing of nuclear RNAs is discussed.", "contents": "[Characteristics of acid ribonuclease from rat thymus chromatin]. Acid ribonuclease, free of nucleases and phosphatases, is isolated from rat thymus chromatin. The pH optimum of the enzyme is 5.0-5.5, optimal concentrations of Na+ and K+ ions are 0.05-0.15 M and 0.05 M respectively, Mg2+ inhibits the enzyme activity. The enzyme hydrolyses poly U, poly AU, cytoplasmic and nuclear RNAs, but does not attack poly A, polyG, polyC, poly A:poly U, native and denatured DNA'S. The enzyme is 3'-endonuclease, it splits the bond between the 5'-carbon atom of adenosine, guanosine and uridine and 3'-phosphate of uridilic residue. Middle length of oligonucleotides after the hydrolysis of cytoplasmic RNA comprises 10 nucleotides. Possible role of the enzyme in the processing of nuclear RNAs is discussed."}
{"id": "PMID:19100", "title": "[Purification of phospholipase C from Bacillus cereus by chromatography on aminoalkylpolysaccharide adsorbents].", "content": "Purification of phospholipase C from Bac. cereus by chromatography on aminoalkylpolysaccharide adsorbents is described. The dependence of the degree of enzyme purification on the amount of ligant and effect of pH and buffer systems on the adsorption-desorption of phospholipase have been studied. At a pH below 9.0 phospholipase C is not retained by the adsorbents and is purified 4-5-fold and up to 23-fold, when aminoalkyl-Sepharose and hexamethylenediamine Sephadex are used respectively. With an increase in the pH value up to 10.0, the enzyme is bound by the adsorbent and is eluted with a 40-90% yield of activity and 7-10-fold purification. The resulting phospholipase C is highly purified and electrophoretically homogeneous. A mechanism of the enzyme-adsorbent interaction is discussed.", "contents": "[Purification of phospholipase C from Bacillus cereus by chromatography on aminoalkylpolysaccharide adsorbents]. Purification of phospholipase C from Bac. cereus by chromatography on aminoalkylpolysaccharide adsorbents is described. The dependence of the degree of enzyme purification on the amount of ligant and effect of pH and buffer systems on the adsorption-desorption of phospholipase have been studied. At a pH below 9.0 phospholipase C is not retained by the adsorbents and is purified 4-5-fold and up to 23-fold, when aminoalkyl-Sepharose and hexamethylenediamine Sephadex are used respectively. With an increase in the pH value up to 10.0, the enzyme is bound by the adsorbent and is eluted with a 40-90% yield of activity and 7-10-fold purification. The resulting phospholipase C is highly purified and electrophoretically homogeneous. A mechanism of the enzyme-adsorbent interaction is discussed."}
{"id": "PMID:19101", "title": "[pH-dependence characteristics of Ca-ATPase activity of heavy meromyosin with modified SH-groups].", "content": "Study of pH-dependence of Ca-ATPase activity of heavy meromyosin (HMM) at low and high ionic strength showed essential differences in the modifying effect of two sulfhydryl reagents, p-CMB and silver. Silver ions in conditions studied independently on pH and KCl concentration produce an inhibition of ATP hydrolysis by myosin and HMM, the shape of the pH-dependence curve remaining similar to that of the native enzyme up to 40% of blocking free sulfhydryl groups. At the same degree of binding of sulfhydryl groups with p-CMB at 0,5 M KCl the pH-dependence curve due to activation at neutral pH changes it's shape and becomes similar to that for dissociation of two ionizable groups (at neutral and alkaline regions). In contrast to this, a low or zero concentrations of KCl no activation was observed for the enzyme with 40-50% of SH-Groups modified by p-CMB and Ca-ATPase in this case seemed to be independent of pH. The data obtained suggest that SH-Groups are not included into the active site of myosin, and the activating effect observed for some sulfhydryl reagents, is due to conformational changes and it can be the result of the penetrance of the organic part of the reagent molecule into hydrophobic region of the protein.", "contents": "[pH-dependence characteristics of Ca-ATPase activity of heavy meromyosin with modified SH-groups]. Study of pH-dependence of Ca-ATPase activity of heavy meromyosin (HMM) at low and high ionic strength showed essential differences in the modifying effect of two sulfhydryl reagents, p-CMB and silver. Silver ions in conditions studied independently on pH and KCl concentration produce an inhibition of ATP hydrolysis by myosin and HMM, the shape of the pH-dependence curve remaining similar to that of the native enzyme up to 40% of blocking free sulfhydryl groups. At the same degree of binding of sulfhydryl groups with p-CMB at 0,5 M KCl the pH-dependence curve due to activation at neutral pH changes it's shape and becomes similar to that for dissociation of two ionizable groups (at neutral and alkaline regions). In contrast to this, a low or zero concentrations of KCl no activation was observed for the enzyme with 40-50% of SH-Groups modified by p-CMB and Ca-ATPase in this case seemed to be independent of pH. The data obtained suggest that SH-Groups are not included into the active site of myosin, and the activating effect observed for some sulfhydryl reagents, is due to conformational changes and it can be the result of the penetrance of the organic part of the reagent molecule into hydrophobic region of the protein."}
{"id": "PMID:19102", "title": "[Regulation of glutamine metabolism in Chlorella pyrenoidosa. Regulation of glutamine synthetase activity by adenylic system components].", "content": "A decrease of glutamine synthetase (E. C. 6.3.1.2.) activity was observed under the assimilation of ammonium nitrogen in Chlorella. At the same time a decrease of ATP content in Chlorella cells took place. The ATP content was 7-fold decreased, while ADP and AMP contents were 4-fold and 3-fold increased respectively, after 15 min. of Chlorella incubation on \"ammonium\" medium. Further incubation for 45 min, resulted in gradual increase of ATP content and in decrease of ADP and AMP contents. The value of energy charge in ammonium assimilating Chlorella cells sharply decreased for first 15 min. of incubation and then it normalized gradually. The experiments with glutamine synthetase preparation, isolated from ammonium assimilating cells, have shown that ADP and AMP are strong inhibitors of the enzyme in the presence of Mg2+, and only ADP produces the inhibitory effect in the presence of Mn2+. No enzyme reactivation was observed after the transfer of ammonium assimilating cells into nitrogen-free medium or nitrate medium, the enzyme activity increasing at the expense of enzyme protein synthesis denovo.", "contents": "[Regulation of glutamine metabolism in Chlorella pyrenoidosa. Regulation of glutamine synthetase activity by adenylic system components]. A decrease of glutamine synthetase (E. C. 6.3.1.2.) activity was observed under the assimilation of ammonium nitrogen in Chlorella. At the same time a decrease of ATP content in Chlorella cells took place. The ATP content was 7-fold decreased, while ADP and AMP contents were 4-fold and 3-fold increased respectively, after 15 min. of Chlorella incubation on \"ammonium\" medium. Further incubation for 45 min, resulted in gradual increase of ATP content and in decrease of ADP and AMP contents. The value of energy charge in ammonium assimilating Chlorella cells sharply decreased for first 15 min. of incubation and then it normalized gradually. The experiments with glutamine synthetase preparation, isolated from ammonium assimilating cells, have shown that ADP and AMP are strong inhibitors of the enzyme in the presence of Mg2+, and only ADP produces the inhibitory effect in the presence of Mn2+. No enzyme reactivation was observed after the transfer of ammonium assimilating cells into nitrogen-free medium or nitrate medium, the enzyme activity increasing at the expense of enzyme protein synthesis denovo."}
{"id": "PMID:19103", "title": "[Oxidation of putrescine, spermidine and spermine by diamino-oxidase from mouse liver].", "content": "Optimal conditions to determine the activity of diaminooxidase in mouse liver homogenate are described. Maximal oxidation rate for putrescine was found to take place at a concentration of 20 mM and pH 9.5, and for spermidine and spermine--at 10 mM concentration and pH 9.2. The rate of tyramine oxidation was maximal at pH 7.8. Apparent KM values were 4.98-10(-3 M, 1-10(-3) M and 0.8-10(-3) M for putrescine, spermidine and spermine respectively. Hydroxylamine did not inhibit the rate of putrescin oxidation at optimal pH value.", "contents": "[Oxidation of putrescine, spermidine and spermine by diamino-oxidase from mouse liver]. Optimal conditions to determine the activity of diaminooxidase in mouse liver homogenate are described. Maximal oxidation rate for putrescine was found to take place at a concentration of 20 mM and pH 9.5, and for spermidine and spermine--at 10 mM concentration and pH 9.2. The rate of tyramine oxidation was maximal at pH 7.8. Apparent KM values were 4.98-10(-3 M, 1-10(-3) M and 0.8-10(-3) M for putrescine, spermidine and spermine respectively. Hydroxylamine did not inhibit the rate of putrescin oxidation at optimal pH value."}
{"id": "PMID:19104", "title": "[Fluorescent properties of b-type ferredoxins].", "content": "Fluroescent spectra of six b-type ferredoxins of plant and animal origins were obtained. All investigated proteins do not contain tryptophan. The emission maxima of the native proteins, apoproteins prepared by various methods, and denaturated proteins are compared. The effects of pH, ionic strength and ferricyanide on the ferredoxins fluorescence were studied. \"Unusual\" emission at 340nm noted previously for adrenal ferredoxin was observed for spinach and Chenopodium album ferredoxins too. The localization of tyrosine fluorescent maximum at 340nm in the ferredoxins is not due to interaction of tyrosine with the iron-sulfur center. The data obtained allow to suggest that the tyrosine residues in ferredoxins have different environments.", "contents": "[Fluorescent properties of b-type ferredoxins]. Fluroescent spectra of six b-type ferredoxins of plant and animal origins were obtained. All investigated proteins do not contain tryptophan. The emission maxima of the native proteins, apoproteins prepared by various methods, and denaturated proteins are compared. The effects of pH, ionic strength and ferricyanide on the ferredoxins fluorescence were studied. \"Unusual\" emission at 340nm noted previously for adrenal ferredoxin was observed for spinach and Chenopodium album ferredoxins too. The localization of tyrosine fluorescent maximum at 340nm in the ferredoxins is not due to interaction of tyrosine with the iron-sulfur center. The data obtained allow to suggest that the tyrosine residues in ferredoxins have different environments."}
{"id": "PMID:19105", "title": "[Relationships of photoreduction of substituted salts of 4,4'-dipyridyl by isolated chloroplasts].", "content": "Kinetic relationships of photoreduction of 4,4'-dimethyldipyridyl and 4,4'-dibenzyldipyridyl in the presence of chlorplast were studied. It was found that photoreduction leads to the establishment of photosteady state in which the rate of photoreduction is equal to the rate of dark oxidation of reduced form. Kinetics of dark oxidation of photoreduced form were investigated. The study of inhibition of photoreduction of methylviologen and potassium ferricyanide by diuron was performed. It was shown that the nature of inhibition of both reactions is completely identical. The effect of hydrogen ions concentration and gas phase composition was studied. Stabilization of low potential electron acceptors to the oxidation by molecular oxygen in the reaction of photooxidation of water is discussed.", "contents": "[Relationships of photoreduction of substituted salts of 4,4'-dipyridyl by isolated chloroplasts]. Kinetic relationships of photoreduction of 4,4'-dimethyldipyridyl and 4,4'-dibenzyldipyridyl in the presence of chlorplast were studied. It was found that photoreduction leads to the establishment of photosteady state in which the rate of photoreduction is equal to the rate of dark oxidation of reduced form. Kinetics of dark oxidation of photoreduced form were investigated. The study of inhibition of photoreduction of methylviologen and potassium ferricyanide by diuron was performed. It was shown that the nature of inhibition of both reactions is completely identical. The effect of hydrogen ions concentration and gas phase composition was studied. Stabilization of low potential electron acceptors to the oxidation by molecular oxygen in the reaction of photooxidation of water is discussed."}
{"id": "PMID:19106", "title": "[Some pathways of biosynthesis and degradation of polyphosphates from green algae Acetabularia mediterranea].", "content": "The activity of ATP: polyphosphate phosphotransferase was detected in free-cellular extracts of Acetabularia mediterranea. The enzyme activity in cells originally deficient in phosphorus and subsequently transferred into the phosphate-containing medium increases 5-10-fold as compared to normal. Polyphosphate degradation in A. mediterranea is probably produced by polyphosphatase, which was also detected in the free-cellular extract. It was shown that the polyphosphatase activity has two pH optima, i.e. 4.5 and 7.5, and is considerably increased when the cells are transferred into the phosphate-free medium. It is assumed that high-molecular polyphosphates involved in A. Mediterranea metabolism are responsible for regulation of orthophosphate and ATP level in the cells by ATP: polyphosphate phosphotransferase and polyphosphatase.", "contents": "[Some pathways of biosynthesis and degradation of polyphosphates from green algae Acetabularia mediterranea]. The activity of ATP: polyphosphate phosphotransferase was detected in free-cellular extracts of Acetabularia mediterranea. The enzyme activity in cells originally deficient in phosphorus and subsequently transferred into the phosphate-containing medium increases 5-10-fold as compared to normal. Polyphosphate degradation in A. mediterranea is probably produced by polyphosphatase, which was also detected in the free-cellular extract. It was shown that the polyphosphatase activity has two pH optima, i.e. 4.5 and 7.5, and is considerably increased when the cells are transferred into the phosphate-free medium. It is assumed that high-molecular polyphosphates involved in A. Mediterranea metabolism are responsible for regulation of orthophosphate and ATP level in the cells by ATP: polyphosphate phosphotransferase and polyphosphatase."}
{"id": "PMID:19107", "title": "[Photophosphorylation, sensitized by chlorophills a and b, pheophytin and beta-carotene in a modelled system].", "content": "In aqueous solutions in air atmosphere chlorophylls a and b, pheophytin and beta-carotene adsorbed on aluminium oxide powder are capable of sensibilizing electron transfer from phosphate ions coupled with the formation of high energy bonds of adenosine phosphates. The highest activity of chlorophylls a and b and pheophytin is observed within the pH range of 7.5-7.8; that of beta-carotene--at pH 7.3-7.5.", "contents": "[Photophosphorylation, sensitized by chlorophills a and b, pheophytin and beta-carotene in a modelled system]. In aqueous solutions in air atmosphere chlorophylls a and b, pheophytin and beta-carotene adsorbed on aluminium oxide powder are capable of sensibilizing electron transfer from phosphate ions coupled with the formation of high energy bonds of adenosine phosphates. The highest activity of chlorophylls a and b and pheophytin is observed within the pH range of 7.5-7.8; that of beta-carotene--at pH 7.3-7.5."}
{"id": "PMID:19109", "title": "Structure and fragmentation mechanisms of some ions in the mass spectrum of ephedrine.", "content": "This paper describes the use of gas chromatography mass spectrometry for the confirmation of ephedrine in adulterated powdered ipecac and ipecac fluid extract. Deuteration studies of ephedrine hydrochloride and some related compounds were also performed in an attempt to postulate structures for some of the fragment ions appearing in the spectrum of ephedrine.", "contents": "Structure and fragmentation mechanisms of some ions in the mass spectrum of ephedrine. This paper describes the use of gas chromatography mass spectrometry for the confirmation of ephedrine in adulterated powdered ipecac and ipecac fluid extract. Deuteration studies of ephedrine hydrochloride and some related compounds were also performed in an attempt to postulate structures for some of the fragment ions appearing in the spectrum of ephedrine."}
{"id": "PMID:19110", "title": "Process engineering studies on immobilized trypsin using molecular sieves as carriers.", "content": "In the present investigation molecular sieve has been found to be a suitable carrier for the immobilization of enzymes. From the present study it may be specifically found that trypsin and pappain can be immobilized by molecular sieve type 4a following a very simple techniqure. The immobilized enzyme can be used both in packed as well as in a continuous stirred tank reactor (CSTR).", "contents": "Process engineering studies on immobilized trypsin using molecular sieves as carriers. In the present investigation molecular sieve has been found to be a suitable carrier for the immobilization of enzymes. From the present study it may be specifically found that trypsin and pappain can be immobilized by molecular sieve type 4a following a very simple techniqure. The immobilized enzyme can be used both in packed as well as in a continuous stirred tank reactor (CSTR)."}
{"id": "PMID:19111", "title": "Properties and biodegradation of a bioemulsifier from Corynebacterium hydrocarboclastus.", "content": "An extracellular polymer was produced by continuous fermentation of Corynebacterium hydrocarboclastus on kerosene in a 24 liter reactor. This polymer was composed of protein, lipid, and carbohydrates. The polymer possessed surface active properties, and had two critical micelle concentrations. Its effectiveness was quite comparable to the effectiveness of synthetic surface active agents such as Tween 80 and Span 20; however, its efficiency was much lower. The polymer also had emulsifying properties. Maximum emulsification was obtained at pH 6. The emulsifying properties were unaffected by high salt concentration [up to 5% (w/v) in Na+], and tolerated a water hardness up to 5,000 ppm. A 2 hr treatment of the polymer at temperatures higher than 65 degrees C resulted in a loss of its emulsifying properties. Two microorganisms, named SLYS and Y, isolated from soil, were able to grow on the polymer as sole carbon and energy source, thus proving its biodegradability. SLYS was tentatively identified as Flavobacterium breve and Y as Flavobacterium devorans.", "contents": "Properties and biodegradation of a bioemulsifier from Corynebacterium hydrocarboclastus. An extracellular polymer was produced by continuous fermentation of Corynebacterium hydrocarboclastus on kerosene in a 24 liter reactor. This polymer was composed of protein, lipid, and carbohydrates. The polymer possessed surface active properties, and had two critical micelle concentrations. Its effectiveness was quite comparable to the effectiveness of synthetic surface active agents such as Tween 80 and Span 20; however, its efficiency was much lower. The polymer also had emulsifying properties. Maximum emulsification was obtained at pH 6. The emulsifying properties were unaffected by high salt concentration [up to 5% (w/v) in Na+], and tolerated a water hardness up to 5,000 ppm. A 2 hr treatment of the polymer at temperatures higher than 65 degrees C resulted in a loss of its emulsifying properties. Two microorganisms, named SLYS and Y, isolated from soil, were able to grow on the polymer as sole carbon and energy source, thus proving its biodegradability. SLYS was tentatively identified as Flavobacterium breve and Y as Flavobacterium devorans."}
{"id": "PMID:19112", "title": "1,4-alpha-Glucan phosphorylase form Klebsiella pneumoniae covalently couple on porous glass.", "content": "A simplified procedure for the preparation of 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae is described. An 80-fold purification is achieved in two steps with an overall yield of about 50%. The specific activity of the homogeneous enzyme protein is 17.7 units/mg. Compared with glycogen phosphorylase from rabbit muscle the enzyme from K. pneumoniae shows a markedly higher stability against deforming and chaotropic agents. The 1,4-alpha-glucan phosphorylase was covalently bound to porous glass particles by three different methods. Coupling with glutaraldehyde gave the highest specific activity, i.e., 5.6 units/mg of bound protein or 133 units/g of glass with maltodextrin as substrate. This corresponds to about 30% of the specific activity of the soluble enzyme. With substrates of higher molecular weight, such as glycogen or amylopectin, lower relative activity was observed. The immobilized enzyme preparations showed pH activity profiles which were slightly displaced to higher values and exhibited an increased temperature stability.", "contents": "1,4-alpha-Glucan phosphorylase form Klebsiella pneumoniae covalently couple on porous glass. A simplified procedure for the preparation of 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae is described. An 80-fold purification is achieved in two steps with an overall yield of about 50%. The specific activity of the homogeneous enzyme protein is 17.7 units/mg. Compared with glycogen phosphorylase from rabbit muscle the enzyme from K. pneumoniae shows a markedly higher stability against deforming and chaotropic agents. The 1,4-alpha-glucan phosphorylase was covalently bound to porous glass particles by three different methods. Coupling with glutaraldehyde gave the highest specific activity, i.e., 5.6 units/mg of bound protein or 133 units/g of glass with maltodextrin as substrate. This corresponds to about 30% of the specific activity of the soluble enzyme. With substrates of higher molecular weight, such as glycogen or amylopectin, lower relative activity was observed. The immobilized enzyme preparations showed pH activity profiles which were slightly displaced to higher values and exhibited an increased temperature stability."}
{"id": "PMID:19114", "title": "Prophylactiv use of propranolol in the Marfan syndrome to prevent aortic dissection.", "content": "Twenty-five patients, 16 men and 9 women, 5-59 years of age with the Marfan syndrome and cardiac complications were started on propranolol over a 6-year period. Propranolol was used as a beta-adrenergic blocking agent to reduce myocardial contractility in an attempt thereby to stay the progression of aortic dilatation and to prevent acute dissection of the aorta. The indications for prophylactic treatment were aortic dilatation, with aortic regurgitation in most cases. It was intended to keep the pulse rate below 70 at all times or below 60 at rest. Propranolol given in daily doses of 120-160 mg caused no side effects. The mean observation time for propranolol treatment in the 25 patients was 3.0 +/- 1.8 years ranging from 1-7 years. In spite of treatment, 5 patients (1 female and 4 males) experienced acute aortic dissection of rupture with fatal outcome. This occurred in 2 patients with the asthenic type, in 2 patients with the nonasthenic type, and in 1 patient with the marfanoid hypermobility syndrome. Serial echocardiograms showed that other patients on propranolol developed increasing dilatation of the aortic root. These observations indicate that propranolol does not necessarily protect against aortic dissection nor stop the progression of the aortic dilatation when cystic medial necrosis of the aorta is already present.", "contents": "Prophylactiv use of propranolol in the Marfan syndrome to prevent aortic dissection. Twenty-five patients, 16 men and 9 women, 5-59 years of age with the Marfan syndrome and cardiac complications were started on propranolol over a 6-year period. Propranolol was used as a beta-adrenergic blocking agent to reduce myocardial contractility in an attempt thereby to stay the progression of aortic dilatation and to prevent acute dissection of the aorta. The indications for prophylactic treatment were aortic dilatation, with aortic regurgitation in most cases. It was intended to keep the pulse rate below 70 at all times or below 60 at rest. Propranolol given in daily doses of 120-160 mg caused no side effects. The mean observation time for propranolol treatment in the 25 patients was 3.0 +/- 1.8 years ranging from 1-7 years. In spite of treatment, 5 patients (1 female and 4 males) experienced acute aortic dissection of rupture with fatal outcome. This occurred in 2 patients with the asthenic type, in 2 patients with the nonasthenic type, and in 1 patient with the marfanoid hypermobility syndrome. Serial echocardiograms showed that other patients on propranolol developed increasing dilatation of the aortic root. These observations indicate that propranolol does not necessarily protect against aortic dissection nor stop the progression of the aortic dilatation when cystic medial necrosis of the aorta is already present."}
{"id": "PMID:19115", "title": "The interaction of some bis-arylhydroxysulphonic acids with a site of known structure in human haemoglobin.", "content": "1 Two bis-arylhydroxysulphonic acids were previously designed to interact with the known molecular configuration of the 2,3-diphosphoglycerate (DPG) receptor-site of human haemoglobin. These compounds liberate oxygen from the haemoglobin similarly to DPG. 2 Solutions of haemoglobin have now been observed under physiological conditions by nuclear magnetic resonance (n.m.r.) in the presence of DPG and of the compounds. 3 Two peaks in the n.m.r. spectrum of haemoglobin are shifted when DPG is added to the solution. 4 The same two peaks in the spectrum are affected by the compounds. 5 The observations are compatible with the predicted interaction between the compounds and the haemoglobin receptor site.", "contents": "The interaction of some bis-arylhydroxysulphonic acids with a site of known structure in human haemoglobin. 1 Two bis-arylhydroxysulphonic acids were previously designed to interact with the known molecular configuration of the 2,3-diphosphoglycerate (DPG) receptor-site of human haemoglobin. These compounds liberate oxygen from the haemoglobin similarly to DPG. 2 Solutions of haemoglobin have now been observed under physiological conditions by nuclear magnetic resonance (n.m.r.) in the presence of DPG and of the compounds. 3 Two peaks in the n.m.r. spectrum of haemoglobin are shifted when DPG is added to the solution. 4 The same two peaks in the spectrum are affected by the compounds. 5 The observations are compatible with the predicted interaction between the compounds and the haemoglobin receptor site."}
{"id": "PMID:19116", "title": "A potent new beta2-adrenoceptor blocking agent.", "content": "1 (t-Butyl-amino-3-ol-2-propyl) oximino-9 fluorene is a new beta2-adrenoceptor blocking agent with a pA2 of 9.23+/-0.25 on isolated trachea. 2 It provokes hypertension in normotensive rats and does not prevent arterial hypertension in SHR rats, although it does prevent the renin secretion normally induced by isoprenaline infusion.", "contents": "A potent new beta2-adrenoceptor blocking agent. 1 (t-Butyl-amino-3-ol-2-propyl) oximino-9 fluorene is a new beta2-adrenoceptor blocking agent with a pA2 of 9.23+/-0.25 on isolated trachea. 2 It provokes hypertension in normotensive rats and does not prevent arterial hypertension in SHR rats, although it does prevent the renin secretion normally induced by isoprenaline infusion."}
{"id": "PMID:19117", "title": "Some observations on the mechanism of benzodiazepine-barbiturate interactions in the mouse.", "content": "1 The prolongation of pentobarbitone sleeping by five benzodiazepines, administered by prior intraperitoneal injection, was measured in mice. The pentobarbitone was injected either intraperitoneally or intracerebroventricularly. For each benzodiazepine, the prolongation was dose-related and differences in potency between benzodiazepines were not marked. 2 The percentage prolongation of sleeping times produced by most of the benzodiazepines was greater when the pentobarbitone was given intracerebroventricularly and was explained by a preferential addition of CNS depressant effects associated with this route. 3 To test whether the action of intraperitoneally administered pentobarbitone had been influenced by a metabolic component, the effects of nitrazepam on drug metabolism, measured by changes in plasma phenazone levels in the mouse, were studied. Nitrazepam (32 mg/kg, i.p.) produced a 23% reduction in the rate of phenazone metabolism. 4 Nitrazepam was also shown to have produced a transient fall in body temperature. Calculations based on Q10 values suggested that this hypothermia accounted, at most, for half the metabolic change measured.", "contents": "Some observations on the mechanism of benzodiazepine-barbiturate interactions in the mouse. 1 The prolongation of pentobarbitone sleeping by five benzodiazepines, administered by prior intraperitoneal injection, was measured in mice. The pentobarbitone was injected either intraperitoneally or intracerebroventricularly. For each benzodiazepine, the prolongation was dose-related and differences in potency between benzodiazepines were not marked. 2 The percentage prolongation of sleeping times produced by most of the benzodiazepines was greater when the pentobarbitone was given intracerebroventricularly and was explained by a preferential addition of CNS depressant effects associated with this route. 3 To test whether the action of intraperitoneally administered pentobarbitone had been influenced by a metabolic component, the effects of nitrazepam on drug metabolism, measured by changes in plasma phenazone levels in the mouse, were studied. Nitrazepam (32 mg/kg, i.p.) produced a 23% reduction in the rate of phenazone metabolism. 4 Nitrazepam was also shown to have produced a transient fall in body temperature. Calculations based on Q10 values suggested that this hypothermia accounted, at most, for half the metabolic change measured."}
{"id": "PMID:19118", "title": "Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats.", "content": "1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors.", "contents": "Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats. 1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors."}
{"id": "PMID:19119", "title": "An evaluation of viability tests of human cadaveric kidneys.", "content": "Cadaveric kidneys are sometimes unsuitable for transplantation because of possible ischaemic damage. The advent of perfusion preservation machines has enabled evaluation of perfusion characteristics and perfusate changes of organs prior to transplantation. This study has evaluated the changes in perfusate pH, lacate dehydrogenase, lactate and free fatty acid utilization in an attempt to identify those kidneys with ischaemic damage. In this investigation no single factor was discriminatory and it was not possible to predict with any degree of certainty those kidneys liable to delayed function or to non-function.", "contents": "An evaluation of viability tests of human cadaveric kidneys. Cadaveric kidneys are sometimes unsuitable for transplantation because of possible ischaemic damage. The advent of perfusion preservation machines has enabled evaluation of perfusion characteristics and perfusate changes of organs prior to transplantation. This study has evaluated the changes in perfusate pH, lacate dehydrogenase, lactate and free fatty acid utilization in an attempt to identify those kidneys with ischaemic damage. In this investigation no single factor was discriminatory and it was not possible to predict with any degree of certainty those kidneys liable to delayed function or to non-function."}
{"id": "PMID:19120", "title": "Where is your vagotomy incomplete? Observations on operative technique.", "content": "There is a trend in gastric surgery towards more selective types of vagotomy but the techniques are more difficult and incomplete nerve section may be more likely. Using the Grassi intra-operative test of mucosal pH, we have studied 50 consecutive patients, 13 having truncal vagotomy, 9 having bilateral selective vagotomy and 28 having proximal gastric vagotomy. We have identified four distinct areas of the stomach where nerve fibres are likely to be left. Three of these can usually be eliminated by careful attention to technique, but the fourth--the distal extent of the parietalcell mass--can only be identified by a precise intra-operative test; this is relevant to proximal gastric vagotomy but not to truncal vagotomy. Unexpected anatomical variations of the vagus nerve branches were found in 8 patients. A precise intra-operative test of residual innervation is particularly helpful in establishing the technique of proximal gastric vagotomy.", "contents": "Where is your vagotomy incomplete? Observations on operative technique. There is a trend in gastric surgery towards more selective types of vagotomy but the techniques are more difficult and incomplete nerve section may be more likely. Using the Grassi intra-operative test of mucosal pH, we have studied 50 consecutive patients, 13 having truncal vagotomy, 9 having bilateral selective vagotomy and 28 having proximal gastric vagotomy. We have identified four distinct areas of the stomach where nerve fibres are likely to be left. Three of these can usually be eliminated by careful attention to technique, but the fourth--the distal extent of the parietalcell mass--can only be identified by a precise intra-operative test; this is relevant to proximal gastric vagotomy but not to truncal vagotomy. Unexpected anatomical variations of the vagus nerve branches were found in 8 patients. A precise intra-operative test of residual innervation is particularly helpful in establishing the technique of proximal gastric vagotomy."}
{"id": "PMID:19122", "title": "Increased exercise tolerance with nitrates in beta-blockaded patients with angina.", "content": "In 14 beta-blockaded anginal subjects, 10 of whom had poor left ventricular function, sublingual isosorbide dinitrate significantly increased maximal exercise capacity on a standardized multistage treadmill test. This was associated with changes in heart rate and blood pressure suggestive of a fall in left ventricular work. The effect of isosorbide lasts for at least two hours and when taken before exercise may be a useful addition to beta-blockade in patients with angina.", "contents": "Increased exercise tolerance with nitrates in beta-blockaded patients with angina. In 14 beta-blockaded anginal subjects, 10 of whom had poor left ventricular function, sublingual isosorbide dinitrate significantly increased maximal exercise capacity on a standardized multistage treadmill test. This was associated with changes in heart rate and blood pressure suggestive of a fall in left ventricular work. The effect of isosorbide lasts for at least two hours and when taken before exercise may be a useful addition to beta-blockade in patients with angina."}
{"id": "PMID:19125", "title": "A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase.", "content": "Immunocytochemical localization of the neurotransmitter synthesizing enzymes, tyrosine and tryptophan hydroxylase, was used to determine whether the noradrenergic neurons in the nucleus locus coeruleus of the rat are innervated by serotonergic (5-HT) neurons. Specific antibodies were prepared to tyrosine hydroxylase, purified from the bovine adrenal medulla, and tryptophan hydroxylase, purified from rat midbrain. These were localized by both light and electron microscopy by the use of the peroxidase-antiperoxidase method. In the nucleus locus coeruleus, tyrosine hydroxylase was contained in the cytoplasm, proximal axons, and dendrites of intrinsic neurons. Tryptophan hydroxylase, on the other hand, was only contained within processes surrounding the perikarya and dendrites of the catecholaminergic neurons. The processes labeled with tryptophan hydroxylase were unmyelinated, ranged in size from 0.1 to 1.4 micron, and consisted of terminal varicosities separated by intervaricose segments. Although in close approximation to noradrenergic neurons, these processes, presumably axons, rarely formed synatic contacts with thickened membrane specializations. In processes, tryptophan hydroxylase was associated with subcellular organelles which had size and distribution of microtubules, and small and large synaptic vesicles. These observations provide a morphological basis to support the hypothesis that the activity of noradrenergic neurons may be modulated by a direct action of 5-HT neurons.", "contents": "A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase. Immunocytochemical localization of the neurotransmitter synthesizing enzymes, tyrosine and tryptophan hydroxylase, was used to determine whether the noradrenergic neurons in the nucleus locus coeruleus of the rat are innervated by serotonergic (5-HT) neurons. Specific antibodies were prepared to tyrosine hydroxylase, purified from the bovine adrenal medulla, and tryptophan hydroxylase, purified from rat midbrain. These were localized by both light and electron microscopy by the use of the peroxidase-antiperoxidase method. In the nucleus locus coeruleus, tyrosine hydroxylase was contained in the cytoplasm, proximal axons, and dendrites of intrinsic neurons. Tryptophan hydroxylase, on the other hand, was only contained within processes surrounding the perikarya and dendrites of the catecholaminergic neurons. The processes labeled with tryptophan hydroxylase were unmyelinated, ranged in size from 0.1 to 1.4 micron, and consisted of terminal varicosities separated by intervaricose segments. Although in close approximation to noradrenergic neurons, these processes, presumably axons, rarely formed synatic contacts with thickened membrane specializations. In processes, tryptophan hydroxylase was associated with subcellular organelles which had size and distribution of microtubules, and small and large synaptic vesicles. These observations provide a morphological basis to support the hypothesis that the activity of noradrenergic neurons may be modulated by a direct action of 5-HT neurons."}
{"id": "PMID:19128", "title": "Behavioral effects of LSD in the cat: proposal of an animal behavior model for studying the actions of hallucinogenic drugs.", "content": "In the course of examining the complete dose-response relationship for the behavioral effects of LSD in the cat, we discovered that, in addition to large increases in investigatory and hallucinatory-like responses, two behaviors, not previously reported, are emitted with a high probability under LSD. Beginning from a baseline of essentially zero in saline-treated animals, limb flicks and abortive grooming increase in frequency in direct relation to the dose of LSD administered (2.5, 10, 25 and 50 microgram/kg i.p.) and then decrease at higher doses (100 and 200 microgram/kg). Limb flicks are a species-specific behavior seen in normal cats almost exclusively in response to the presence of a foreign substance, such as water, on the hindpaw or forepaw. In abortive grooming, the cat orients to the body surfaces as if to groom but does not emit the consummatory grooming response (bite, lick or scratch), or emits the response in midair. These behaviors can serve as an animal behavior model for the actions of LSD and related hallucinogens in humans. The specificity of these behavioral changes is indicated by the fact that they are never seen in response to other classes of psychoactive drugs such as D-amphetamine, atropine, caffeine, and cholorpheniramine. They are, however, elicited by compounds such as psilocybin which are structurally and functionally  related to LSD. The validity of the model is based on evidence indicating that it is: specific to hallucinogens, dose dependent, observed in a dose range effective in humans, parallels the major parameters of the actions of LSD in humans (see following paper), sensitive, robust, reliable, quantifiable and easy to score.", "contents": "Behavioral effects of LSD in the cat: proposal of an animal behavior model for studying the actions of hallucinogenic drugs. In the course of examining the complete dose-response relationship for the behavioral effects of LSD in the cat, we discovered that, in addition to large increases in investigatory and hallucinatory-like responses, two behaviors, not previously reported, are emitted with a high probability under LSD. Beginning from a baseline of essentially zero in saline-treated animals, limb flicks and abortive grooming increase in frequency in direct relation to the dose of LSD administered (2.5, 10, 25 and 50 microgram/kg i.p.) and then decrease at higher doses (100 and 200 microgram/kg). Limb flicks are a species-specific behavior seen in normal cats almost exclusively in response to the presence of a foreign substance, such as water, on the hindpaw or forepaw. In abortive grooming, the cat orients to the body surfaces as if to groom but does not emit the consummatory grooming response (bite, lick or scratch), or emits the response in midair. These behaviors can serve as an animal behavior model for the actions of LSD and related hallucinogens in humans. The specificity of these behavioral changes is indicated by the fact that they are never seen in response to other classes of psychoactive drugs such as D-amphetamine, atropine, caffeine, and cholorpheniramine. They are, however, elicited by compounds such as psilocybin which are structurally and functionally  related to LSD. The validity of the model is based on evidence indicating that it is: specific to hallucinogens, dose dependent, observed in a dose range effective in humans, parallels the major parameters of the actions of LSD in humans (see following paper), sensitive, robust, reliable, quantifiable and easy to score."}
{"id": "PMID:19132", "title": "[Influence of age and sex on the acute toxicity of two steroid anesthetics in rats].", "content": "During the newborn period, there is a hight increase of the acute toxicity of two steroid anaesthetics (Hydroxydione, Althesin) given by intraperitoneal route on the rat as also an influence of hormonal conditions.", "contents": "[Influence of age and sex on the acute toxicity of two steroid anesthetics in rats]. During the newborn period, there is a hight increase of the acute toxicity of two steroid anaesthetics (Hydroxydione, Althesin) given by intraperitoneal route on the rat as also an influence of hormonal conditions."}
{"id": "PMID:19133", "title": "[Lysine decarboxylase in Pseudomonas aeruginosa].", "content": "The research of lysine, ornithine and arginine decarboxylases has been made for 50 strains of fluorescent Pseudomonas (P. aeruginosa, P. fluorescens, P. putida). By thin layer chromatography, all the strains of Pseudomonas aeruginosa and the fifth of the strains of P. putida had lysine decarboxylase activity at alcaline pH (optimal pH 8) ; Pseudomonas fluorescens did not produce this decarboxylase. Arginine and ornithine decarboxylase are absent for all the strains of fluorescent Pseudomonas.", "contents": "[Lysine decarboxylase in Pseudomonas aeruginosa]. The research of lysine, ornithine and arginine decarboxylases has been made for 50 strains of fluorescent Pseudomonas (P. aeruginosa, P. fluorescens, P. putida). By thin layer chromatography, all the strains of Pseudomonas aeruginosa and the fifth of the strains of P. putida had lysine decarboxylase activity at alcaline pH (optimal pH 8) ; Pseudomonas fluorescens did not produce this decarboxylase. Arginine and ornithine decarboxylase are absent for all the strains of fluorescent Pseudomonas."}
{"id": "PMID:19134", "title": "Cathepsin D activity in isolated odontoblasts.", "content": "The presence of an acid proteinase with a high activity has been demonstrated in isolated odontoblast-predentine material from dentinogenically active rat incisors. The enzyme was identified as cathepsin D (EC 3.4.23.5). The possible significance of the enzymatic degradation of proteoglycans and glycosaminoglycans in the course of the calcification process is discussed.", "contents": "Cathepsin D activity in isolated odontoblasts. The presence of an acid proteinase with a high activity has been demonstrated in isolated odontoblast-predentine material from dentinogenically active rat incisors. The enzyme was identified as cathepsin D (EC 3.4.23.5). The possible significance of the enzymatic degradation of proteoglycans and glycosaminoglycans in the course of the calcification process is discussed."}
{"id": "PMID:19135", "title": "An in vitro and in vivo investigation of mellitate and ethane-1-hydroxy-1,1-diphosphonate in calcium phosphate systems.", "content": "Comparisons of mellitate (MA) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) have been carried out in studies of enamel etching, calcium phosphate crystal growth and animal calculus deposition. In enamel etch studies at pH 5, 6, or 7 and after treatment times of 5 or 170 min, EHDP was less damaging to enamel surfaces than MA as determined by scanning electron microscopy, grazing angle electron diffraction, and quantitative etch solution analyses. Both MA and EHDP inhibited hydroxyapatite crystal growth, although EHDP was more effective than MA. The formation of a tricalcium mellitate surface phase is suggested as the basis of the MA crystal growth effect on apatite. Both MA and EHDP also inhibited rat calculus formation, but EHDP was more effective than MA. The relation between crystal growth inhibition, surface phase solubility, and anti-calculus activity is discussed and a generalized principal for determining an effective inhibitor of calculus is suggested.", "contents": "An in vitro and in vivo investigation of mellitate and ethane-1-hydroxy-1,1-diphosphonate in calcium phosphate systems. Comparisons of mellitate (MA) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) have been carried out in studies of enamel etching, calcium phosphate crystal growth and animal calculus deposition. In enamel etch studies at pH 5, 6, or 7 and after treatment times of 5 or 170 min, EHDP was less damaging to enamel surfaces than MA as determined by scanning electron microscopy, grazing angle electron diffraction, and quantitative etch solution analyses. Both MA and EHDP inhibited hydroxyapatite crystal growth, although EHDP was more effective than MA. The formation of a tricalcium mellitate surface phase is suggested as the basis of the MA crystal growth effect on apatite. Both MA and EHDP also inhibited rat calculus formation, but EHDP was more effective than MA. The relation between crystal growth inhibition, surface phase solubility, and anti-calculus activity is discussed and a generalized principal for determining an effective inhibitor of calculus is suggested."}
{"id": "PMID:19136", "title": "Pentose-shunt oxidation in the periosteal cells in healing fractures.", "content": "The activity of pentose-shunt dehydrogenases is very low in periosteal cells of normal rat metatarsals, but increases one day post-fracture and rises linearly over the next two days. By four days post-fracture, the distribution of this activity along the bone shows two centres of high activity: the first in the region of proliferation to form callus and the second at the site where new bone is first seen, one day later. The high rate of generation of NADPH would be expected to reduce glutathione; reduced glutathione has been shown to inhibit alkaline phosphatase activity in these cells.", "contents": "Pentose-shunt oxidation in the periosteal cells in healing fractures. The activity of pentose-shunt dehydrogenases is very low in periosteal cells of normal rat metatarsals, but increases one day post-fracture and rises linearly over the next two days. By four days post-fracture, the distribution of this activity along the bone shows two centres of high activity: the first in the region of proliferation to form callus and the second at the site where new bone is first seen, one day later. The high rate of generation of NADPH would be expected to reduce glutathione; reduced glutathione has been shown to inhibit alkaline phosphatase activity in these cells."}
{"id": "PMID:19137", "title": "The inhibition of calcium oxalate crystal growth by multidentate organic phosphonates.", "content": "The effect of a number of structurally related multidentate organic phosphonates on the rate of crystal growth of calcium oxalate was studied as a function of pH. Rate constants were obtained at various concentrations for the phosphonates ethane-1-hydroxy-1,1-diphosphonate (EHDP), nitrilotri(methylenephosphonic acid) (NTMP), N,N,N',N'-ethylene-diaminetetra(methylenephosphonic acid) (ENTNP), and N,N,N',N'-hexamethylenediaminetetra(methylenephosphonic acid (HMTMP), at pH 5.00, 6.00, and 7.00. The effect of pH on the inhibitory activity of each of the phosphonates was considerable with effective concentrations of inhibitor decreasing two orders of magnitude, in some cases, as the pH was increased. At a given pH the potentially hexadentate ligands, ENTMP and HMTMP, were generally the most effective inhibitors. The results suggested that EHDP, at currently administered doses, provides only a moderate increase in the capacity of human urine to inhibit calcium oxalate crystal growth.", "contents": "The inhibition of calcium oxalate crystal growth by multidentate organic phosphonates. The effect of a number of structurally related multidentate organic phosphonates on the rate of crystal growth of calcium oxalate was studied as a function of pH. Rate constants were obtained at various concentrations for the phosphonates ethane-1-hydroxy-1,1-diphosphonate (EHDP), nitrilotri(methylenephosphonic acid) (NTMP), N,N,N',N'-ethylene-diaminetetra(methylenephosphonic acid) (ENTNP), and N,N,N',N'-hexamethylenediaminetetra(methylenephosphonic acid (HMTMP), at pH 5.00, 6.00, and 7.00. The effect of pH on the inhibitory activity of each of the phosphonates was considerable with effective concentrations of inhibitor decreasing two orders of magnitude, in some cases, as the pH was increased. At a given pH the potentially hexadentate ligands, ENTMP and HMTMP, were generally the most effective inhibitors. The results suggested that EHDP, at currently administered doses, provides only a moderate increase in the capacity of human urine to inhibit calcium oxalate crystal growth."}
{"id": "PMID:19138", "title": "Comparative toxicities of enflurane, fluroxene and nitrous oxide at subanaesthetic concentrations in laboratory animals.", "content": "We compared the toxicities of subanesthetic concentrations of fluroxene, enflurane and nitrous oxide in mice, rats and guinea pigs which were in an active growth phase. Fluroxene produced a greater mortality and decrement in weight gain than enflurane and nitrous oxide despite administration of far lower concentrations. Enflurane, 0.1 MAC, resulted in a detrimental effect on weight and early mortality in mice but not in rats or guinea pigs. Nitrous oxide, 0.1 MAC, resulted in only a minor effect on weight gain in guinea pigs and an increased incidence of focal inflammatory liver changes in mice. No consistent injury to any organs other than liver or kidney were found.", "contents": "Comparative toxicities of enflurane, fluroxene and nitrous oxide at subanaesthetic concentrations in laboratory animals. We compared the toxicities of subanesthetic concentrations of fluroxene, enflurane and nitrous oxide in mice, rats and guinea pigs which were in an active growth phase. Fluroxene produced a greater mortality and decrement in weight gain than enflurane and nitrous oxide despite administration of far lower concentrations. Enflurane, 0.1 MAC, resulted in a detrimental effect on weight and early mortality in mice but not in rats or guinea pigs. Nitrous oxide, 0.1 MAC, resulted in only a minor effect on weight gain in guinea pigs and an increased incidence of focal inflammatory liver changes in mice. No consistent injury to any organs other than liver or kidney were found."}
{"id": "PMID:19139", "title": "Identification of beta adrenergic receptors in rat hypothalamus.", "content": "(-)-[3H]-Dihydroalprenolol((-)[3H]DHA) binding in the rat hypothalamus appears to possess all the characteristics expected of physiologically relevant beta-adrenergic receptors. Binding of (-)-[3H]DHA to the hypothalamic sites was rapid (k1 = 1.3 X 10(-7) min-1) and also rapidly reversible. Binding was saturable at low concentrations of ligand (approximately 50-100 nM). The dissociation constant (KD) of (-)-[3H]DHA binding determined by equilibrium analysis was 19 nM. Binding displayed beta-adrenergic specificity. beta-Adrenergic agonists inhibited binding in the following order of potency: (-)-isoproterenol congruent to (-)-epinephrine greater than (-)-norepinephrine. Specific beta-adrenergic antagonists (-)-propranol and (-)-alprenolol inhibited binding at low concentrations (KD = 25-50nM) whereas the alpha-antagonist phentolamine inhibited binding at very high concentration (KD = 42 micron). Interactions of both agonists and antagonists with the sites showed stereoselectivity. The (-)-isomers of all beta-adrenergic agents tested were more potent than their respective (+)-isomers. These results suggest that specific receptor sites for beta-adrenergic catecholamines are present in rat hypothalamus.", "contents": "Identification of beta adrenergic receptors in rat hypothalamus. (-)-[3H]-Dihydroalprenolol((-)[3H]DHA) binding in the rat hypothalamus appears to possess all the characteristics expected of physiologically relevant beta-adrenergic receptors. Binding of (-)-[3H]DHA to the hypothalamic sites was rapid (k1 = 1.3 X 10(-7) min-1) and also rapidly reversible. Binding was saturable at low concentrations of ligand (approximately 50-100 nM). The dissociation constant (KD) of (-)-[3H]DHA binding determined by equilibrium analysis was 19 nM. Binding displayed beta-adrenergic specificity. beta-Adrenergic agonists inhibited binding in the following order of potency: (-)-isoproterenol congruent to (-)-epinephrine greater than (-)-norepinephrine. Specific beta-adrenergic antagonists (-)-propranol and (-)-alprenolol inhibited binding at low concentrations (KD = 25-50nM) whereas the alpha-antagonist phentolamine inhibited binding at very high concentration (KD = 42 micron). Interactions of both agonists and antagonists with the sites showed stereoselectivity. The (-)-isomers of all beta-adrenergic agents tested were more potent than their respective (+)-isomers. These results suggest that specific receptor sites for beta-adrenergic catecholamines are present in rat hypothalamus."}
{"id": "PMID:19143", "title": "Resolution of rat renin substrates by isoelectric focusing.", "content": "Pooled plasmas from normal or binephrectomized rats and perfusates of isolated livers were used as sources of renin substrate for isoelectric focusing. After desalting, preliminary fractionation (plasma only), and concentration, the preparations were focused in a pH 3--10 gradient on 20-cm glass plates layered with Sephadex slurry. The pH 4--6 region, containing all the substrate, was scraped from this plate and refocused in a pH 4--6 gradient. Substrate content of 1-cm strips of slurry from half of the plate was determined by both radioimmunoassay and bioassay of angiotensin resulting from incubation with added renin. Corresponding strips from the other half of the plate were incubated without renin as a control for any preformed angiotensin. The asymmetry and broad distribution (pH 4--5) of substrate from different sources suggested the existence of more than one form. Higher resolution achieved by using the high substrate concentration of postnephrectomy plasma and 0.5-cm strips of slurry on 20-cm or 40-cm plates revealed peaks and shoulders of substrate activity. Our data suggest that multiple forms of substrate are synthesized by the liver and circulate in plasma. Postnephrectomy rat plasma appears to contain relatively more substrate(s) with higher isoelectric points than in normal plasma, possibly an accumulation of forms ordinarily degraded by endogenous renal renin.", "contents": "Resolution of rat renin substrates by isoelectric focusing. Pooled plasmas from normal or binephrectomized rats and perfusates of isolated livers were used as sources of renin substrate for isoelectric focusing. After desalting, preliminary fractionation (plasma only), and concentration, the preparations were focused in a pH 3--10 gradient on 20-cm glass plates layered with Sephadex slurry. The pH 4--6 region, containing all the substrate, was scraped from this plate and refocused in a pH 4--6 gradient. Substrate content of 1-cm strips of slurry from half of the plate was determined by both radioimmunoassay and bioassay of angiotensin resulting from incubation with added renin. Corresponding strips from the other half of the plate were incubated without renin as a control for any preformed angiotensin. The asymmetry and broad distribution (pH 4--5) of substrate from different sources suggested the existence of more than one form. Higher resolution achieved by using the high substrate concentration of postnephrectomy plasma and 0.5-cm strips of slurry on 20-cm or 40-cm plates revealed peaks and shoulders of substrate activity. Our data suggest that multiple forms of substrate are synthesized by the liver and circulate in plasma. Postnephrectomy rat plasma appears to contain relatively more substrate(s) with higher isoelectric points than in normal plasma, possibly an accumulation of forms ordinarily degraded by endogenous renal renin."}
{"id": "PMID:19144", "title": "Preparation and galactosyltransferase acceptor activity of derivatives of antifreeze glycoproteins of an Antarctic fish.", "content": "A series of 12 closely related glycoproteins containing alpha-linked N-acetyl-D-galactosamine (GalNAc) as the sole carbohydrate moiety have been prepared by degradation of the antifreeze glycoproteins from the serum of the Antarctic fish Trematomus borchgrevinki. The polypeptide moieties of these glycoproteins contain substitutions in the normal -Ala-Ala-Thr- repeating tripeptide sequence which introduce alterations in the amount of alpha-helical structure and the density of acceptor sites, and theoretically also in the amount of rigidity, polarity, and hydrophobicity of the polypeptide. Of these alterations only density of acceptor sites has a statistically significant effect on the ability of the GalNAc alpha leads to Thr moiety to act as a substrate for galactosyltransferase (EC 2.4.1.22) activity solubilized from rat liver microsomes. This result suggests that in the biosynthesis of rat liver glycoproteins these structural features of the polypeptide moiety of glycoproteins are not part of the substrate specificity of the galactosyltransferase activity that transfers the second monosaccharide. Hence, these structural features do not play a major role in determining the structure of the threonine-linked oligosaccharide after its synthesis has been initiated.", "contents": "Preparation and galactosyltransferase acceptor activity of derivatives of antifreeze glycoproteins of an Antarctic fish. A series of 12 closely related glycoproteins containing alpha-linked N-acetyl-D-galactosamine (GalNAc) as the sole carbohydrate moiety have been prepared by degradation of the antifreeze glycoproteins from the serum of the Antarctic fish Trematomus borchgrevinki. The polypeptide moieties of these glycoproteins contain substitutions in the normal -Ala-Ala-Thr- repeating tripeptide sequence which introduce alterations in the amount of alpha-helical structure and the density of acceptor sites, and theoretically also in the amount of rigidity, polarity, and hydrophobicity of the polypeptide. Of these alterations only density of acceptor sites has a statistically significant effect on the ability of the GalNAc alpha leads to Thr moiety to act as a substrate for galactosyltransferase (EC 2.4.1.22) activity solubilized from rat liver microsomes. This result suggests that in the biosynthesis of rat liver glycoproteins these structural features of the polypeptide moiety of glycoproteins are not part of the substrate specificity of the galactosyltransferase activity that transfers the second monosaccharide. Hence, these structural features do not play a major role in determining the structure of the threonine-linked oligosaccharide after its synthesis has been initiated."}
{"id": "PMID:19146", "title": "The role of cyclic nucleotides in the CNS.", "content": "On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre-or post-synaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intrcellular injection techniques should minimize this particular problem, although possibly at the expense of new diffulties. Prio blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Utimately, the developement of highly specific inhibitor for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the action of cyclic GMP and the role of its synthesizing enzyme, guanylate cyclase. The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.", "contents": "The role of cyclic nucleotides in the CNS. On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre-or post-synaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intrcellular injection techniques should minimize this particular problem, although possibly at the expense of new diffulties. Prio blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Utimately, the developement of highly specific inhibitor for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the action of cyclic GMP and the role of its synthesizing enzyme, guanylate cyclase. The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature."}
{"id": "PMID:19147", "title": "Future of anesthesia.", "content": "The authors present an account of some of the problems facing the specialty of anesthesia, which suggests that the interdependence of these problems and of their solutions should be recognized. Recruitment, job satisfaction and clinical standards will be improved as a result of greater involvement by anesthetists in preanesthetic care as part of the health care team. Teaching programs require appropriate expansion and modification. The incorporation of a physician-assistant program is essential to the future of anesthesia.", "contents": "Future of anesthesia. The authors present an account of some of the problems facing the specialty of anesthesia, which suggests that the interdependence of these problems and of their solutions should be recognized. Recruitment, job satisfaction and clinical standards will be improved as a result of greater involvement by anesthetists in preanesthetic care as part of the health care team. Teaching programs require appropriate expansion and modification. The incorporation of a physician-assistant program is essential to the future of anesthesia."}
{"id": "PMID:19148", "title": "The trauma of being psychotic: a neglected element in the management of chronic schizophrenia?", "content": "A hypothesis is put forward in regards to what is called \"chronic schizophrenia\" that those observations which suggest a continuing disease process may turn out not to be intrinsic facets of schizophrenia as a neurochemical instability but rather neurotic reactions to the acute schizophrenic process. The hypothesis goes on to suggest that this reaction to the acute psychosis is such as to constitute a traumatic neurosis and that while controlling the psychosis with an \"umbrella\" of major tranquilizers, it is possible to resolve this neurosis. Resolution of the neurosis requires a particular approach to therapy. This is a hypothesis which is very much open to experimental examination and one which may, if proven, markedly affect the postpsychosis management of schizophrenia.", "contents": "The trauma of being psychotic: a neglected element in the management of chronic schizophrenia? A hypothesis is put forward in regards to what is called \"chronic schizophrenia\" that those observations which suggest a continuing disease process may turn out not to be intrinsic facets of schizophrenia as a neurochemical instability but rather neurotic reactions to the acute schizophrenic process. The hypothesis goes on to suggest that this reaction to the acute psychosis is such as to constitute a traumatic neurosis and that while controlling the psychosis with an \"umbrella\" of major tranquilizers, it is possible to resolve this neurosis. Resolution of the neurosis requires a particular approach to therapy. This is a hypothesis which is very much open to experimental examination and one which may, if proven, markedly affect the postpsychosis management of schizophrenia."}
{"id": "PMID:19149", "title": "Desensitization therapy for body image anxiety.", "content": "A newly devised therapy technique to desensitize individuals for body image anxiety arising from conversion symptoms and psychophysiologic disorders is outlined. One application involves the projective use of inkblots with high anatomical content which provide a source of visual input to stimulate somatic images in consciousness. When these are activated in a state of relaxation the anxiety content of the pathologic anatomical imagery is reduced. A case history involving desensitization treatment for a psychoneurotic patient's psychophysiologic symptom of premature ejaculation is cited. It is primarily designed to alert interested clinical investigators to this technical innovation in treatment.", "contents": "Desensitization therapy for body image anxiety. A newly devised therapy technique to desensitize individuals for body image anxiety arising from conversion symptoms and psychophysiologic disorders is outlined. One application involves the projective use of inkblots with high anatomical content which provide a source of visual input to stimulate somatic images in consciousness. When these are activated in a state of relaxation the anxiety content of the pathologic anatomical imagery is reduced. A case history involving desensitization treatment for a psychoneurotic patient's psychophysiologic symptom of premature ejaculation is cited. It is primarily designed to alert interested clinical investigators to this technical innovation in treatment."}
{"id": "PMID:19150", "title": "The ability of enteric bacteria to catalyze the covalent binding of bile acids and cholesterol to DNA and their in ability to metabolize benzo(a)pyrene to a binding product and to known metabolites.", "content": "The capacity of enteric bacteria (E. coli, Salmonella, Pseudomonas, Shigella and Klebsiella) to catalyze the covalent binding of benzo(a)pyrene (BP), cholic acid, deoxycholic acid and cholesterol was investigated. In general, these bacteria were incapable of activating BP to a covalently bound product with calf thymus DNA. Metabolism studies of BP by fluorometric assay failed to indicate any accumulation of BP-3-hydroxy in the incubation medium. Detailed metabolic investigation with high-pressure liquid chromatography indicated that these bacteria did not produce any known metabolites which are formed by mammalian systems. However, radioactivity was detected in all fractions, suggesting that the bacteria were readily metabolizing BP into smaller molecules for energy and carbon sources. Although the enteric bacteria did not metabolize BP into known metabolites, some were capable of activating cholesterol, cholic acid and deoxycholic acid to covalently bound products with DNA. The binding data with cholesterol and bile acids also suggested that the binding process required NADPH as a cofactor because binding level was rather low without NADPH.", "contents": "The ability of enteric bacteria to catalyze the covalent binding of bile acids and cholesterol to DNA and their in ability to metabolize benzo(a)pyrene to a binding product and to known metabolites. The capacity of enteric bacteria (E. coli, Salmonella, Pseudomonas, Shigella and Klebsiella) to catalyze the covalent binding of benzo(a)pyrene (BP), cholic acid, deoxycholic acid and cholesterol was investigated. In general, these bacteria were incapable of activating BP to a covalently bound product with calf thymus DNA. Metabolism studies of BP by fluorometric assay failed to indicate any accumulation of BP-3-hydroxy in the incubation medium. Detailed metabolic investigation with high-pressure liquid chromatography indicated that these bacteria did not produce any known metabolites which are formed by mammalian systems. However, radioactivity was detected in all fractions, suggesting that the bacteria were readily metabolizing BP into smaller molecules for energy and carbon sources. Although the enteric bacteria did not metabolize BP into known metabolites, some were capable of activating cholesterol, cholic acid and deoxycholic acid to covalently bound products with DNA. The binding data with cholesterol and bile acids also suggested that the binding process required NADPH as a cofactor because binding level was rather low without NADPH."}
{"id": "PMID:19152", "title": "Beta-adrenoceptor antagonists and the release of creatine phosphokinase from hypoxic heart muscle.", "content": "The ability of several beta-adrenoceptor antagonists with partial agonist activity (dl-oxprenolol, dl-acebutolol and dl-practolol) to attenuate the release of CPK that occurs during hypoxia (pO2 less than 0.8 kPa [6 MMHg]) has been studied and compared with the protection provided by dl-propranolol. dl-propranolol attenuated the hypoxic-induced release of CPK. The activity resided in the l isomer. dl-oxprenolol, acebutolol, and practolol were either less effective than propranolol in preventing CPK release, or they exacerbated the release. The protective effect of dl-propranolol extended to the hypoxic hyperthyroid heart but not to hearts that were perfused under aerobic (pO2 greater than 80 kPa [600 mmHg]) Ca2+-free conditions.", "contents": "Beta-adrenoceptor antagonists and the release of creatine phosphokinase from hypoxic heart muscle. The ability of several beta-adrenoceptor antagonists with partial agonist activity (dl-oxprenolol, dl-acebutolol and dl-practolol) to attenuate the release of CPK that occurs during hypoxia (pO2 less than 0.8 kPa [6 MMHg]) has been studied and compared with the protection provided by dl-propranolol. dl-propranolol attenuated the hypoxic-induced release of CPK. The activity resided in the l isomer. dl-oxprenolol, acebutolol, and practolol were either less effective than propranolol in preventing CPK release, or they exacerbated the release. The protective effect of dl-propranolol extended to the hypoxic hyperthyroid heart but not to hearts that were perfused under aerobic (pO2 greater than 80 kPa [600 mmHg]) Ca2+-free conditions."}
{"id": "PMID:19154", "title": "The nature of the rate-limiting step in aniline hydroxylation involving cytochrome p-450 rat liver microsomes.", "content": "The kinetics of aniline hydroxylation was studied with: (1) rat liver microsomes involving NADPH and O2 (system 1), (2) hepatic microsomes and tert-butylhydroperoxide (system 2) and (3) microsomes and cumyl hydroperoxide (system 3) at 15--37 degrees C. The reactions were characterized by the values of the aniline oxidation rate constants, k2 = V/E0, where E0 is the initial concentration of cytochrome P-450: K 1/2 = 1.60 - 10(8) EXP (-13 400/RT) sec-1, k 2/2 = 1.66 - 10(9) exp (-14 500/RT) sec-1, k 3/2 = 6.83 - 10(9) exp (-15 300/RT) sec-1. The values of delta H0 and delta S0, were calculated and compared for the three systems. The evidence suggests that oxygen insertion into the substrate molecule is the rate-limiting step in the reaction of aniline oxidation for the mentioned systems. The nature of aniline binding to cytochrome P-450 and that of the hydroxylating agent have been discussed.", "contents": "The nature of the rate-limiting step in aniline hydroxylation involving cytochrome p-450 rat liver microsomes. The kinetics of aniline hydroxylation was studied with: (1) rat liver microsomes involving NADPH and O2 (system 1), (2) hepatic microsomes and tert-butylhydroperoxide (system 2) and (3) microsomes and cumyl hydroperoxide (system 3) at 15--37 degrees C. The reactions were characterized by the values of the aniline oxidation rate constants, k2 = V/E0, where E0 is the initial concentration of cytochrome P-450: K 1/2 = 1.60 - 10(8) EXP (-13 400/RT) sec-1, k 2/2 = 1.66 - 10(9) exp (-14 500/RT) sec-1, k 3/2 = 6.83 - 10(9) exp (-15 300/RT) sec-1. The values of delta H0 and delta S0, were calculated and compared for the three systems. The evidence suggests that oxygen insertion into the substrate molecule is the rate-limiting step in the reaction of aniline oxidation for the mentioned systems. The nature of aniline binding to cytochrome P-450 and that of the hydroxylating agent have been discussed."}
{"id": "PMID:19157", "title": "[Splenogonadal fusion].", "content": "The authors report of case of splenogonadic fusion in abdominal retention, revising the subject from the aetiopathogenetic and diagnostic point of view. It is emphasized that correct recognition of the lesion can obviate useless orchiectomies, preserving normal function of the testicle at least from the endocrinal standpoint.", "contents": "[Splenogonadal fusion]. The authors report of case of splenogonadic fusion in abdominal retention, revising the subject from the aetiopathogenetic and diagnostic point of view. It is emphasized that correct recognition of the lesion can obviate useless orchiectomies, preserving normal function of the testicle at least from the endocrinal standpoint."}
{"id": "PMID:19160", "title": "[Properties of chlorotetrolic acid and its ester as possible protein acetylenic reagents].", "content": "Chlorotetrolic acid and, even better, the corresponding methyl ester react under mild conditions with different functional groups. The relative ease with which the same nucleophile adds to the triple bond and substitutes the chlorine was studied and the stability of the addition products was compared.", "contents": "[Properties of chlorotetrolic acid and its ester as possible protein acetylenic reagents]. Chlorotetrolic acid and, even better, the corresponding methyl ester react under mild conditions with different functional groups. The relative ease with which the same nucleophile adds to the triple bond and substitutes the chlorine was studied and the stability of the addition products was compared."}
{"id": "PMID:19163", "title": "Nucleotide pyrophosphatase and phosphodiesterase. I. Organ distribution and activities in body fluids.", "content": "We estimated nucleotide pyrophosphatase and phosphodiesterase I activities in human and rat organs and in body fluids from man and dog. The highest organ activities were found in epididymis, kidney, liver, and intestine. In body fluids, the activity was highest in seminal plasma, followed by intestinal lymph, serum, heart lymph, cerebrospinal fluid, milk, and urine. The ratio nucleotide pyrophosphatase/phosphodiesterase I and the urea resistance of phosphodiesterase I differed among human organs, body fluids, and blood cells. Different isoenzymes probably exist. The activities in serum share several properties with those in several organs--e.g. pH-optimum 9.6-9.8, dependency on Zn2+, and the effects of inhibitors. Phosphodiesterase I in erythrocytes, which has not been described previously, differs from enzyme from other sources by lower pH optimum (8.5), dependency on Mg2+, inhibition by Zn2+, and stimulation by dithiothreitol.", "contents": "Nucleotide pyrophosphatase and phosphodiesterase. I. Organ distribution and activities in body fluids. We estimated nucleotide pyrophosphatase and phosphodiesterase I activities in human and rat organs and in body fluids from man and dog. The highest organ activities were found in epididymis, kidney, liver, and intestine. In body fluids, the activity was highest in seminal plasma, followed by intestinal lymph, serum, heart lymph, cerebrospinal fluid, milk, and urine. The ratio nucleotide pyrophosphatase/phosphodiesterase I and the urea resistance of phosphodiesterase I differed among human organs, body fluids, and blood cells. Different isoenzymes probably exist. The activities in serum share several properties with those in several organs--e.g. pH-optimum 9.6-9.8, dependency on Zn2+, and the effects of inhibitors. Phosphodiesterase I in erythrocytes, which has not been described previously, differs from enzyme from other sources by lower pH optimum (8.5), dependency on Mg2+, inhibition by Zn2+, and stimulation by dithiothreitol."}
{"id": "PMID:19164", "title": "Temperature dependence of the absorbance of alkaline solutions of 4-nitrophenyl phosphate--a potential source of error in the measurement of alkaline phosphatase activity.", "content": "The absorbance of an alkaline solution of 4-nitrophenyl phosphate is a function of temperature. Quantitative evaluation of this phenomenon indicates that it (a) depends on the concentration of the compound and is independent of source, buffer concentration, and pH above 9.0; (b) is reversible; (c) is not a result of alkaline hydrolysis or 4-nitrophenol contamination; and (d) correlates with a temperature-induced shift of its absorbance spectrum. The phenomenon may represent a potential analytical problem in methods for alkaline phosphatase in which this compound is the substrate. If thermal equilibrium is not reached and maintained during an alkaline phosphatase assay, the thermochromic response will be included in the measured rate. The magnitude of this error depends on the thermal response and control characteristics of each particular instrument and the reaction conditions under which such an analysis is performed.", "contents": "Temperature dependence of the absorbance of alkaline solutions of 4-nitrophenyl phosphate--a potential source of error in the measurement of alkaline phosphatase activity. The absorbance of an alkaline solution of 4-nitrophenyl phosphate is a function of temperature. Quantitative evaluation of this phenomenon indicates that it (a) depends on the concentration of the compound and is independent of source, buffer concentration, and pH above 9.0; (b) is reversible; (c) is not a result of alkaline hydrolysis or 4-nitrophenol contamination; and (d) correlates with a temperature-induced shift of its absorbance spectrum. The phenomenon may represent a potential analytical problem in methods for alkaline phosphatase in which this compound is the substrate. If thermal equilibrium is not reached and maintained during an alkaline phosphatase assay, the thermochromic response will be included in the measured rate. The magnitude of this error depends on the thermal response and control characteristics of each particular instrument and the reaction conditions under which such an analysis is performed."}
{"id": "PMID:19165", "title": "Continuous-flow analysis for glucose, triglycerides, and ATP with immobilized enzymes in tubular form.", "content": "Small-bore (\"Autozyme\") tubes with immobilized enzymes at the inner wall have been developed and studied for application in the Technicon \"SMAC\" high-speed continuous-flow biochemical analyzer. Tubes coated with glucose oxidase (D-glucose:oxygen oxidoreductase, EC 1.1.3.4) have been prepared for the assay of glucose, with colorimetric assay of the hydrogen peroxide produced; tubes coated with glycerol kinase (ATP:glycerol phosphotransferase, EC 2.7.1.30) for the enzymatic assay of triglycerides; tubes coated with hexokinase (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1) and glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NAD+ oxidoreductase EC 1.1.1.49) for the measurement of ATP, an intermediate product in assays for creatine kinase. With use of 10-15 cm lengths of Autozyme tube and SMAC hydraulics (150 samples per hour), assay sensitivity and carryover were similar to values for the corresponding free-enzyme methods. These immobilized enzymes were sufficiently stable for one to eight weeks of continuous use before replacemnt. We conclude that suitable bound-enzyme tubes can replace either single or multiple free-enzyme reagents in many continuous-flow assays at high sampling rates.", "contents": "Continuous-flow analysis for glucose, triglycerides, and ATP with immobilized enzymes in tubular form. Small-bore (\"Autozyme\") tubes with immobilized enzymes at the inner wall have been developed and studied for application in the Technicon \"SMAC\" high-speed continuous-flow biochemical analyzer. Tubes coated with glucose oxidase (D-glucose:oxygen oxidoreductase, EC 1.1.3.4) have been prepared for the assay of glucose, with colorimetric assay of the hydrogen peroxide produced; tubes coated with glycerol kinase (ATP:glycerol phosphotransferase, EC 2.7.1.30) for the enzymatic assay of triglycerides; tubes coated with hexokinase (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1) and glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NAD+ oxidoreductase EC 1.1.1.49) for the measurement of ATP, an intermediate product in assays for creatine kinase. With use of 10-15 cm lengths of Autozyme tube and SMAC hydraulics (150 samples per hour), assay sensitivity and carryover were similar to values for the corresponding free-enzyme methods. These immobilized enzymes were sufficiently stable for one to eight weeks of continuous use before replacemnt. We conclude that suitable bound-enzyme tubes can replace either single or multiple free-enzyme reagents in many continuous-flow assays at high sampling rates."}
{"id": "PMID:19166", "title": "Creatine kinase: re-examination of optimum reaction conditions.", "content": "I have re-examined optimum reaction conditions for measurement of creatine kinase (EC 2.7.3.2). The optimum pH is 6.45, and 2,2-bis(hydroxymethyl)-2,2',2''-nitrotriethanol acetate, 200 mmol/liter, is the buffer of choice. Thioglycerol, 20 mmol/liter, is superior for both in-assay reactivation and for storage stability of sera. Fluoride, 25 mmol/liter, a broad inactivator of adenylate kinase (EC 2.7.4.3), has little effect on creatine kinase and is superior to AMP for adenylate kinase inhibition in the assay of creatine kinase. Magnesium ion, ADP, and buffer concentrations are interdependent and their optima must be determined together. The hexokinase/glucose-6-phosphate dehydrogenase activity ratio should not exceed 1.6. The range of linearity is limited by the glucose-6-phosphate dehydrogenase and NAD+ concentrations. Glucose-6-phosphate dehydrogenase, ADP, and NAD+ are the constituents most likely to result in unacceptable blanks. Creatine kinase is inhibited noncompetitively by anions: acetate and fluoride inhibit slightly, but sulfates, nitrates, and excessive chlorides should be avoided.", "contents": "Creatine kinase: re-examination of optimum reaction conditions. I have re-examined optimum reaction conditions for measurement of creatine kinase (EC 2.7.3.2). The optimum pH is 6.45, and 2,2-bis(hydroxymethyl)-2,2',2''-nitrotriethanol acetate, 200 mmol/liter, is the buffer of choice. Thioglycerol, 20 mmol/liter, is superior for both in-assay reactivation and for storage stability of sera. Fluoride, 25 mmol/liter, a broad inactivator of adenylate kinase (EC 2.7.4.3), has little effect on creatine kinase and is superior to AMP for adenylate kinase inhibition in the assay of creatine kinase. Magnesium ion, ADP, and buffer concentrations are interdependent and their optima must be determined together. The hexokinase/glucose-6-phosphate dehydrogenase activity ratio should not exceed 1.6. The range of linearity is limited by the glucose-6-phosphate dehydrogenase and NAD+ concentrations. Glucose-6-phosphate dehydrogenase, ADP, and NAD+ are the constituents most likely to result in unacceptable blanks. Creatine kinase is inhibited noncompetitively by anions: acetate and fluoride inhibit slightly, but sulfates, nitrates, and excessive chlorides should be avoided."}
{"id": "PMID:19167", "title": "pH and the activity of porphobilinogen synthase in human blood.", "content": "For determination of the activity of this enzyme (EC 4.2.1.24) in blood, pH dependency was evaluated by using whole blood and washed erythrocytes. The effects of assay methods, original and final pH, and use of sodium or potassium phosphate buffer were examined. The pattern of pH dependency differed for whole blood and washed erythrocytes, whether blood from normal or lead-exposed subjects was examined. The pH optimum for the activity in erythrocytes from lead-exposed subjects was the same as for the normal persons if the concentration of lead in blood did not exceed 80 microgram/100 g of whole blood. Hemolyzing blood by placing it on solid CO2 decreases the activity.", "contents": "pH and the activity of porphobilinogen synthase in human blood. For determination of the activity of this enzyme (EC 4.2.1.24) in blood, pH dependency was evaluated by using whole blood and washed erythrocytes. The effects of assay methods, original and final pH, and use of sodium or potassium phosphate buffer were examined. The pattern of pH dependency differed for whole blood and washed erythrocytes, whether blood from normal or lead-exposed subjects was examined. The pH optimum for the activity in erythrocytes from lead-exposed subjects was the same as for the normal persons if the concentration of lead in blood did not exceed 80 microgram/100 g of whole blood. Hemolyzing blood by placing it on solid CO2 decreases the activity."}
{"id": "PMID:19168", "title": "Evaluation of ampouled tonometered buffer solutions as a quality-control system for pH, pCO2, and pO2 measurement.", "content": "In response to the need for an adequate quality-control system for blood-pH and blood-gas analyzers, we investigated the practical application of ampouled phosphate-bicarbonate-chloride solutions tonometered with mixtures of carbon dioxide, oxygen, and nitrogen. This system offers three discrete sets of pH, pCO2, AND PO2 values, which are consistent with normal and pathophysiologically high and low values. The stated values were based on the U.S. National Bureau of Standards scale for pH and on gas analysis for pCO2 and pO2. Influence of temperature, air contact, calibration gas, and storage was established. Internal and external quality control by means of these ampoules is presented. The system is stable, accurate, precise, and suitable for simultaneous quality control of pH, pCO2, and pO2 measurements.", "contents": "Evaluation of ampouled tonometered buffer solutions as a quality-control system for pH, pCO2, and pO2 measurement. In response to the need for an adequate quality-control system for blood-pH and blood-gas analyzers, we investigated the practical application of ampouled phosphate-bicarbonate-chloride solutions tonometered with mixtures of carbon dioxide, oxygen, and nitrogen. This system offers three discrete sets of pH, pCO2, AND PO2 values, which are consistent with normal and pathophysiologically high and low values. The stated values were based on the U.S. National Bureau of Standards scale for pH and on gas analysis for pCO2 and pO2. Influence of temperature, air contact, calibration gas, and storage was established. Internal and external quality control by means of these ampoules is presented. The system is stable, accurate, precise, and suitable for simultaneous quality control of pH, pCO2, and pO2 measurements."}
{"id": "PMID:19169", "title": "Sensitive, optimized assay for serum AMP deaminase.", "content": "A sensitive, optimized assay for serum AMP deaminase (EC 3.5.4.6) is presented, which is based on a colorimetric indophenol determination of ammonia liberated during the enzyme reaction. An average enzyme activity in serum of 2.7 U/liter (n = 36, range 0-6.2) for healthy adults was established. Both the enzyme and colorimetric reactions were optimized to give an assay sensitivity of 0.2 U/liter of serum, a 98-99% analytical recovery in the normal serum enzyme concentration range, and a CV of 7.9% in-run and 10.6% between-run. This optimization included studies on specific buffer, pH, ionic strength, and potential activators. The Km for the enzyme in serum was determinated to be 1.4 X 10(-3) mol/liter, which agrees well with the value reported for human skeletal muscle enzyme. Above-normal serum AMP deaminase activity may be present in various myopathies and could be useful in detecting carriers of the X-linked dystrophies.", "contents": "Sensitive, optimized assay for serum AMP deaminase. A sensitive, optimized assay for serum AMP deaminase (EC 3.5.4.6) is presented, which is based on a colorimetric indophenol determination of ammonia liberated during the enzyme reaction. An average enzyme activity in serum of 2.7 U/liter (n = 36, range 0-6.2) for healthy adults was established. Both the enzyme and colorimetric reactions were optimized to give an assay sensitivity of 0.2 U/liter of serum, a 98-99% analytical recovery in the normal serum enzyme concentration range, and a CV of 7.9% in-run and 10.6% between-run. This optimization included studies on specific buffer, pH, ionic strength, and potential activators. The Km for the enzyme in serum was determinated to be 1.4 X 10(-3) mol/liter, which agrees well with the value reported for human skeletal muscle enzyme. Above-normal serum AMP deaminase activity may be present in various myopathies and could be useful in detecting carriers of the X-linked dystrophies."}
{"id": "PMID:19170", "title": "Semiautomated spectrophotometry of total phospholipids in plasma.", "content": "A one-stage semiautomated method for estimating total phospholipids in plasma is reported. The phospholipids are extracted into aqueous ethanol, combined with a Lewis acid, and the change in pH is monitored colorimetrically. The method, compared with the acid digestion method of Gomori [J. Lab. Clin. Med. 27, 955 (1942)], gives results that are about 0.25 mmol/liter lower, but seems to be a suitable and less hazardous alternative.", "contents": "Semiautomated spectrophotometry of total phospholipids in plasma. A one-stage semiautomated method for estimating total phospholipids in plasma is reported. The phospholipids are extracted into aqueous ethanol, combined with a Lewis acid, and the change in pH is monitored colorimetrically. The method, compared with the acid digestion method of Gomori [J. Lab. Clin. Med. 27, 955 (1942)], gives results that are about 0.25 mmol/liter lower, but seems to be a suitable and less hazardous alternative."}
{"id": "PMID:19171", "title": "Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency.", "content": "Detailed studies, using gas chromatography and mass spectrometric methods, of the urinary organic acids excreted by a patient with proven pyruvate decarboxylase deficiency are reported. In addition to the greatly-increased levels of lactate and pyruvate, marked elevation in the levels of 2-oxoglutaric, malic, and isocitric acids were observed, with associated increases 2-hydroxyglutaric, fumaric, succinic, and glyceric acids, and reduced citric acid excretion. The levels of excretion during clinically static and acute periods are compared to those in a normal neonate and normal infants. The metabolites observed indicate a probable defect in the oxidation of pyruvate by pyruvate dehydrogenase and suggest the presence of secondary defects in the tricarboxylic acid cycle. Studies of this type may enable the relatively rapid identification of the probable underlying enzyme deficiency in cases of congenital lactic acidosis, prior to confirmatory enzyme studies.", "contents": "Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency. Detailed studies, using gas chromatography and mass spectrometric methods, of the urinary organic acids excreted by a patient with proven pyruvate decarboxylase deficiency are reported. In addition to the greatly-increased levels of lactate and pyruvate, marked elevation in the levels of 2-oxoglutaric, malic, and isocitric acids were observed, with associated increases 2-hydroxyglutaric, fumaric, succinic, and glyceric acids, and reduced citric acid excretion. The levels of excretion during clinically static and acute periods are compared to those in a normal neonate and normal infants. The metabolites observed indicate a probable defect in the oxidation of pyruvate by pyruvate dehydrogenase and suggest the presence of secondary defects in the tricarboxylic acid cycle. Studies of this type may enable the relatively rapid identification of the probable underlying enzyme deficiency in cases of congenital lactic acidosis, prior to confirmatory enzyme studies."}
{"id": "PMID:19172", "title": "A gel filament as an analytical tool: the testing of an affinity chromatographic, product-immobilizing linear gel for determination of enzymatic activity.", "content": "A new technique for quantitative analysis is proposed. An underfined volume of the test solution is exposed to a reagent in the form of a gel filament of capillary dimensions. The linear progress in the gel of the compound in question is followed with the aid of the coloured reaction products deposited along its path. With the use of the enzyme gamma-glutamyl transpeptidase it is shown that the velocity in the system of the component to be analysed, as determined by measurement of its coloured track, is related to its activity in the test solution.", "contents": "A gel filament as an analytical tool: the testing of an affinity chromatographic, product-immobilizing linear gel for determination of enzymatic activity. A new technique for quantitative analysis is proposed. An underfined volume of the test solution is exposed to a reagent in the form of a gel filament of capillary dimensions. The linear progress in the gel of the compound in question is followed with the aid of the coloured reaction products deposited along its path. With the use of the enzyme gamma-glutamyl transpeptidase it is shown that the velocity in the system of the component to be analysed, as determined by measurement of its coloured track, is related to its activity in the test solution."}
{"id": "PMID:19173", "title": "An automated continuous-monitoring procedure for the determination of acid phosphatase activity in serum.", "content": "The method of Hillmann, in which hydrolysis of alpha-naphthyl phosphate by acid phosphatase is coupled to the formation of an alpha-naphthol-Fast Red TR azo-compound, has been adapted for use with the LKB Produkter AB 8600 reaction rate analyzer. Factors which affect the reproducibility of the method are described and its performance is shown to be superior to that of a manual phenyl-phosphate procedure.", "contents": "An automated continuous-monitoring procedure for the determination of acid phosphatase activity in serum. The method of Hillmann, in which hydrolysis of alpha-naphthyl phosphate by acid phosphatase is coupled to the formation of an alpha-naphthol-Fast Red TR azo-compound, has been adapted for use with the LKB Produkter AB 8600 reaction rate analyzer. Factors which affect the reproducibility of the method are described and its performance is shown to be superior to that of a manual phenyl-phosphate procedure."}
{"id": "PMID:19174", "title": "A method for visual assessment of the performance of components in a continuous flow system.", "content": "When two reagents are mixed in a continuous flow system it is difficult to detect variations in their proportions in the individual liquid segments because such variations produce only small changes in the final colour intensity. A method is described whereby these differences in reagent proportion produce a different pH in each segment and, by the addition of an appropriate pH indicator solution, a different colour for each segment. This method may be used to demonstrate the eveness of reagent injection, reagent mixing and segment/segment interaction associated with continuous flow systems.", "contents": "A method for visual assessment of the performance of components in a continuous flow system. When two reagents are mixed in a continuous flow system it is difficult to detect variations in their proportions in the individual liquid segments because such variations produce only small changes in the final colour intensity. A method is described whereby these differences in reagent proportion produce a different pH in each segment and, by the addition of an appropriate pH indicator solution, a different colour for each segment. This method may be used to demonstrate the eveness of reagent injection, reagent mixing and segment/segment interaction associated with continuous flow systems."}
{"id": "PMID:19175", "title": "Calcium in bile and calcium salts in gallstones.", "content": "In gallbladder and common duct bile from patients undergoing cholecystectomy, usually because of gallstones, calcium was found to exist in at least 2 forms. Ultrafiltration showed some calcium was bound to substances with a molecular weight greater than 10 000, and the chief binding agent is likely to be the mixed micelle. Bound calcium was significantly less in common duct bile than in bile from functioning gallbladders, but the amount of ultrafiltrable calcium was the same. Furthermore, ultrafiltrable calcium in gallbladder bile from patients with cholesterol or some calcium carbonate in their gallstones was almost constant for a range of total calcium concentrations of 2.40--9.70 mmol/l. Comparison of ultrafiltrable and total calcium values for the different types of stone-formers showed that the deposition of calcium carbonate in gallstones was not related to any calcium measurement made. However, the presence of calcium phosphate and/or calcium bilirubinate in gallstones could be related to a significant increase in ultrafiltrable calcium in gallbladder bile.", "contents": "Calcium in bile and calcium salts in gallstones. In gallbladder and common duct bile from patients undergoing cholecystectomy, usually because of gallstones, calcium was found to exist in at least 2 forms. Ultrafiltration showed some calcium was bound to substances with a molecular weight greater than 10 000, and the chief binding agent is likely to be the mixed micelle. Bound calcium was significantly less in common duct bile than in bile from functioning gallbladders, but the amount of ultrafiltrable calcium was the same. Furthermore, ultrafiltrable calcium in gallbladder bile from patients with cholesterol or some calcium carbonate in their gallstones was almost constant for a range of total calcium concentrations of 2.40--9.70 mmol/l. Comparison of ultrafiltrable and total calcium values for the different types of stone-formers showed that the deposition of calcium carbonate in gallstones was not related to any calcium measurement made. However, the presence of calcium phosphate and/or calcium bilirubinate in gallstones could be related to a significant increase in ultrafiltrable calcium in gallbladder bile."}
{"id": "PMID:19176", "title": "A method for enhancing the stability of thiol-containing enzymes immobilised on nylon.", "content": "The limited stability of immobilised enzymes is a major factor restricting their use in clinical chemistry. The immobilisation procedure described here affords a simple method of enhancing the stability of certain enzymes immobilised on nylon. Studies with alcohol dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase have indicated that a significant increase in stability can be obtained using this immobilisation procedure as compared with conventional procedures. As anticipated the immobilisation procedure was unsatisfactory for oxidases such as glucose oxidase.", "contents": "A method for enhancing the stability of thiol-containing enzymes immobilised on nylon. The limited stability of immobilised enzymes is a major factor restricting their use in clinical chemistry. The immobilisation procedure described here affords a simple method of enhancing the stability of certain enzymes immobilised on nylon. Studies with alcohol dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase have indicated that a significant increase in stability can be obtained using this immobilisation procedure as compared with conventional procedures. As anticipated the immobilisation procedure was unsatisfactory for oxidases such as glucose oxidase."}
{"id": "PMID:19177", "title": "The activity of gamma-glutamyl transferase in the serum of multiple sclerosis and other neurological diseases.", "content": "1. In the sera of 142 neurological patients, including 35 cases with multiple sclerosis (MS), and 20 normal controls the gamma-glutamyltransferase (gamma-GT) activity was determined. The result of this investigation was compared with the \"combined hippuric acid test\" formely often used in MS patients. 2. The MS patients are the only group which significantly differs from the normal controls. There are also small differences between them and some of the other neurological patient groups. About one-third of the MS patients show moderately pathological serum activities. On the other hand, patients with a definite liver affection, especially chronic alcoholics, regularly show an even more important elevation of the values, which makes this test a sensitive tool for the screening of alcohol-induced liver intoxications. 3. Although the gamma-GT test in not quite as sensitive in indicating organic defects in MS patients, it seems to reflected a disturbed liver function in the same way as the more complicated \"combined hippuric acid test\". It may therefore be used as a simple tool of finding and following up organic defects in MS patients.", "contents": "The activity of gamma-glutamyl transferase in the serum of multiple sclerosis and other neurological diseases. 1. In the sera of 142 neurological patients, including 35 cases with multiple sclerosis (MS), and 20 normal controls the gamma-glutamyltransferase (gamma-GT) activity was determined. The result of this investigation was compared with the \"combined hippuric acid test\" formely often used in MS patients. 2. The MS patients are the only group which significantly differs from the normal controls. There are also small differences between them and some of the other neurological patient groups. About one-third of the MS patients show moderately pathological serum activities. On the other hand, patients with a definite liver affection, especially chronic alcoholics, regularly show an even more important elevation of the values, which makes this test a sensitive tool for the screening of alcohol-induced liver intoxications. 3. Although the gamma-GT test in not quite as sensitive in indicating organic defects in MS patients, it seems to reflected a disturbed liver function in the same way as the more complicated \"combined hippuric acid test\". It may therefore be used as a simple tool of finding and following up organic defects in MS patients."}
{"id": "PMID:19179", "title": "Determination of enteropeptidase activity in human duodenal aspirates.", "content": "A sensitive procedure is described for the determination in duodenal aspirates of enteropeptidase activity based on the activation of trypsinogen and the estimation of trypsin formed with benzoyl-arginine-p-nitroanilide. Using the recovery approach where a known amount of purified human enteropeptidase is diluted in duodenal fluid and the recoverable activity determined, this method was shown to give a sensitive and reliable estimate of the enteropeptidase activity in duodenal fluid although it was shown that the enzyme was subject to a 10% activation by components in the duodenal fluid. The reported 5-fold stimulation of enteropeptidase activity by bile salts could not be demonstrated.", "contents": "Determination of enteropeptidase activity in human duodenal aspirates. A sensitive procedure is described for the determination in duodenal aspirates of enteropeptidase activity based on the activation of trypsinogen and the estimation of trypsin formed with benzoyl-arginine-p-nitroanilide. Using the recovery approach where a known amount of purified human enteropeptidase is diluted in duodenal fluid and the recoverable activity determined, this method was shown to give a sensitive and reliable estimate of the enteropeptidase activity in duodenal fluid although it was shown that the enzyme was subject to a 10% activation by components in the duodenal fluid. The reported 5-fold stimulation of enteropeptidase activity by bile salts could not be demonstrated."}
{"id": "PMID:19180", "title": "Bile lysosomal enzymes: characteristics and pathological significance for various hepatobiliary disorders.", "content": "The activities of several glycosidases (beta-galactosidase, beta-glucosidase, N-acetyl-beta-glucosaminidase) were demonstrated in human bile. The enzyme activities are increased about 100 times after exclusion of bile salts and other small molecular compounds by Sephadex G-50 gel filtration. The use of 4-methylumbelliferyl derivatives as substrates was useful as measurement of the bile enzyme activities are not altered in the presence of bile pigments. Enzyme characteristics of bile glycosidases were determined: pH optimum and isoelectric point. The bile glycosidase activities were also measured in various hepatobiliary disorders (cholelithiasis, cancer of gallbladder, acute hepatitis, liver cirrhosis and fatty liver). The glycosidase activities in bile from patients with liver diseases, as well as with cholelithiasis, were generally decreased. Isoelectric focusing patterns of biliary glycosidases were similar for specimens from patients with hepatobiliary disorders as compared to normal.", "contents": "Bile lysosomal enzymes: characteristics and pathological significance for various hepatobiliary disorders. The activities of several glycosidases (beta-galactosidase, beta-glucosidase, N-acetyl-beta-glucosaminidase) were demonstrated in human bile. The enzyme activities are increased about 100 times after exclusion of bile salts and other small molecular compounds by Sephadex G-50 gel filtration. The use of 4-methylumbelliferyl derivatives as substrates was useful as measurement of the bile enzyme activities are not altered in the presence of bile pigments. Enzyme characteristics of bile glycosidases were determined: pH optimum and isoelectric point. The bile glycosidase activities were also measured in various hepatobiliary disorders (cholelithiasis, cancer of gallbladder, acute hepatitis, liver cirrhosis and fatty liver). The glycosidase activities in bile from patients with liver diseases, as well as with cholelithiasis, were generally decreased. Isoelectric focusing patterns of biliary glycosidases were similar for specimens from patients with hepatobiliary disorders as compared to normal."}
{"id": "PMID:19181", "title": "[Glycogen synthase activity in parodontal disease (author's transl)].", "content": "A biochemical study of an enzyme participating in the synthesis of glycogen is presented, with particular regard to the fluctuations in the amounts of this polysaccharide in human gingival epithelium, during inflammation. The increase in the activity of UDPglucose : glycogen glucosyltransferase can be related to the accumulation of glycogen. Some kinetic parameters of this enzyme are described.", "contents": "[Glycogen synthase activity in parodontal disease (author's transl)]. A biochemical study of an enzyme participating in the synthesis of glycogen is presented, with particular regard to the fluctuations in the amounts of this polysaccharide in human gingival epithelium, during inflammation. The increase in the activity of UDPglucose : glycogen glucosyltransferase can be related to the accumulation of glycogen. Some kinetic parameters of this enzyme are described."}
{"id": "PMID:19183", "title": "Suitability of commercial enzyme control sera for the quality control of activity determinations of L-aspartate aminotransferase and L-alanine aminotransferase in human serum.", "content": "Details of a systematic approach to suitability testing of commercial control sera are given for substrate optimized L-aspartate aminotransferase and L-alanine aminotransferase methods at 37 degrees C. Their acceptability for control purposes of standardized methods depends on: (1) the range of control values in relation to borderline values, (2) stability, (3) aspect, clarity, (4) NADH consumption in preincubation time, (5) blank activities, (6) kinetic data as half saturation constants and saturation curves, (7) influence of effectors, (8) isoenzyme pattern. These evaluation criteria are proposed for suitability testing. The term \"representativeness\" should be introduced as a special criterion for main characteristics of control materials. The authors want to point out the close connection with standardization of methods.", "contents": "Suitability of commercial enzyme control sera for the quality control of activity determinations of L-aspartate aminotransferase and L-alanine aminotransferase in human serum. Details of a systematic approach to suitability testing of commercial control sera are given for substrate optimized L-aspartate aminotransferase and L-alanine aminotransferase methods at 37 degrees C. Their acceptability for control purposes of standardized methods depends on: (1) the range of control values in relation to borderline values, (2) stability, (3) aspect, clarity, (4) NADH consumption in preincubation time, (5) blank activities, (6) kinetic data as half saturation constants and saturation curves, (7) influence of effectors, (8) isoenzyme pattern. These evaluation criteria are proposed for suitability testing. The term \"representativeness\" should be introduced as a special criterion for main characteristics of control materials. The authors want to point out the close connection with standardization of methods."}
{"id": "PMID:19184", "title": "A sensitive fluorescence assay for the simultaneous and separate determination of arylsulphatases A and B.", "content": "A sensitive fluorometric assay utilizing 4-methylumbelliferyl sulphate has been developed for the simultaneous determination of arylsulphatases A and B from leucocytes, based on the differential effect of silver ions on the two enzymes. The procedure allows discrimination between normal cases and those with metachromatic leucodystrophy.", "contents": "A sensitive fluorescence assay for the simultaneous and separate determination of arylsulphatases A and B. A sensitive fluorometric assay utilizing 4-methylumbelliferyl sulphate has been developed for the simultaneous determination of arylsulphatases A and B from leucocytes, based on the differential effect of silver ions on the two enzymes. The procedure allows discrimination between normal cases and those with metachromatic leucodystrophy."}
{"id": "PMID:19187", "title": "Clinical consequences of polymorphic acetylation of basic drugs.", "content": "The clinical consequences (therapeutic and toxic) of drug acetylation polymorphism are reviewed for procainamide, hydralazine, phenelzine, isoniazid, and salicylazosulfapyridine. Genetic slow acetylators are more likely than rapid acetylators to experience the following adverse drug reactions: (1) earlier development of procainamide-induced antinuclear antibody; (2) earlier and more frequent development of procainamide-induced systemic lupus erythematosus (SLE); (3) hydralazine-induced SLE; (4) spontaneous SLE; (5) drowsiness and nausea from phenelzine; (6) cyanosis, hemolysis, and transient reticulocytosis from salicylazosulfapyridine; and (7) polyneuropathy after isoniazid therapy. The incidence of isoniazid hepatitis may, however, be more common in rapid than than in slow acetylators. Genetic slow acetylators are also more likely than rapid acetylators to experience greater therapeutic responses from similar doses of the following: phenelzine, hydralazine provided beta blockers are concurrently used, and isoniazid if once weekly therapy is used. Thus, knowledge of the acetylator phenotype of a patient can help determine the relative risk for some drug-related toxic and therapeutic responses.", "contents": "Clinical consequences of polymorphic acetylation of basic drugs. The clinical consequences (therapeutic and toxic) of drug acetylation polymorphism are reviewed for procainamide, hydralazine, phenelzine, isoniazid, and salicylazosulfapyridine. Genetic slow acetylators are more likely than rapid acetylators to experience the following adverse drug reactions: (1) earlier development of procainamide-induced antinuclear antibody; (2) earlier and more frequent development of procainamide-induced systemic lupus erythematosus (SLE); (3) hydralazine-induced SLE; (4) spontaneous SLE; (5) drowsiness and nausea from phenelzine; (6) cyanosis, hemolysis, and transient reticulocytosis from salicylazosulfapyridine; and (7) polyneuropathy after isoniazid therapy. The incidence of isoniazid hepatitis may, however, be more common in rapid than than in slow acetylators. Genetic slow acetylators are also more likely than rapid acetylators to experience greater therapeutic responses from similar doses of the following: phenelzine, hydralazine provided beta blockers are concurrently used, and isoniazid if once weekly therapy is used. Thus, knowledge of the acetylator phenotype of a patient can help determine the relative risk for some drug-related toxic and therapeutic responses."}
{"id": "PMID:19188", "title": "Effect of antacids on absorption of clorazepate.", "content": "The effect of a magnesia and alumina antacid suspension on the absorption of clorazepate dipotassium was studied in 15 normal healthy adult subjects who ingested a 15-mg dose of clorazepate alone or with single or multiple doses of antacid. The results of this three-period randomized complete crossover study showed a trend of initially slower absorption and lower peak nordiazepam plasma levels when administered with the antacid suspension. However, there were no significant differences among treatments in the extent of absorption as measured by the area under the plasma level-time curves. Clorazepate plasma levels were of relatively short duration and similar for all treatments. The urinary excretion pattern was likewise comparable with conjugated oxazepam, the major species measured. Plasma elimination half-lives of nordiazepam and clorazepate were not affected by the antacid treatments.", "contents": "Effect of antacids on absorption of clorazepate. The effect of a magnesia and alumina antacid suspension on the absorption of clorazepate dipotassium was studied in 15 normal healthy adult subjects who ingested a 15-mg dose of clorazepate alone or with single or multiple doses of antacid. The results of this three-period randomized complete crossover study showed a trend of initially slower absorption and lower peak nordiazepam plasma levels when administered with the antacid suspension. However, there were no significant differences among treatments in the extent of absorption as measured by the area under the plasma level-time curves. Clorazepate plasma levels were of relatively short duration and similar for all treatments. The urinary excretion pattern was likewise comparable with conjugated oxazepam, the major species measured. Plasma elimination half-lives of nordiazepam and clorazepate were not affected by the antacid treatments."}
{"id": "PMID:19189", "title": "Leukocyte cyclic adenosine monophosphate in asthmatic children. Effects of adrenergic therapy.", "content": "Blood specimens for measurement of leukocyte cyclic adenosine monophosphate (AMP) were obtained at weekly intervals from asthmatic children who were participating in a double-blind, crossover study to compare the effects of two adrenergic agents and a placebo. When patients were treated with the placebo, the basal measurements and the cyclic AMP responses of leukocytes to in vitro stimulation with epinephrine (10(-4) M) were similar to those of normal subjects but within one week after initiation of treatment with an adrenergic bronchodilator, leukocyte cyclic AMP responses to adrenergic stimulation in vitro decreased and remained low during the remainder of the treatment period. Within one week after discontinuation of adrenergic therapy, leukocyte cyclic AMP responses returned to the control level. Our results indicate that the alterations in leukocyte cyclic AMP metabolism which have been observed previously in asthmatic patients may result from medications used for treatment of asthma.", "contents": "Leukocyte cyclic adenosine monophosphate in asthmatic children. Effects of adrenergic therapy. Blood specimens for measurement of leukocyte cyclic adenosine monophosphate (AMP) were obtained at weekly intervals from asthmatic children who were participating in a double-blind, crossover study to compare the effects of two adrenergic agents and a placebo. When patients were treated with the placebo, the basal measurements and the cyclic AMP responses of leukocytes to in vitro stimulation with epinephrine (10(-4) M) were similar to those of normal subjects but within one week after initiation of treatment with an adrenergic bronchodilator, leukocyte cyclic AMP responses to adrenergic stimulation in vitro decreased and remained low during the remainder of the treatment period. Within one week after discontinuation of adrenergic therapy, leukocyte cyclic AMP responses returned to the control level. Our results indicate that the alterations in leukocyte cyclic AMP metabolism which have been observed previously in asthmatic patients may result from medications used for treatment of asthma."}
{"id": "PMID:19186", "title": "Equine angiotensin converting enzyme: a zinc metalloenzyme.", "content": "1. Angiotensin I converting enzyme from horse plasma has been extensively purified and shown to be homogeneous by disc-gel electrophoresis. 2. The metal ion involved in the catalytic reaction of the enzyme has been identified for the first time as zinc by atomic absorption spectrometry. 3. A number of other physicochemical properties of the enzyme are described and compared with results obtained by other investigators. The molecular weight was determined by gel filtration to be 113 000 daltons. The pH maximum was found to be 7-4. The chloride activation of the enzyme appears to act by facilitation of substrate binding to the enzyme. 4. By use of enzyme inhibitors, tyrosine has been implicated as a functional residue at the active site of the enzyme. 5. The enzyme shows a fairly high degree of specificity towards its substrates.", "contents": "Equine angiotensin converting enzyme: a zinc metalloenzyme. 1. Angiotensin I converting enzyme from horse plasma has been extensively purified and shown to be homogeneous by disc-gel electrophoresis. 2. The metal ion involved in the catalytic reaction of the enzyme has been identified for the first time as zinc by atomic absorption spectrometry. 3. A number of other physicochemical properties of the enzyme are described and compared with results obtained by other investigators. The molecular weight was determined by gel filtration to be 113 000 daltons. The pH maximum was found to be 7-4. The chloride activation of the enzyme appears to act by facilitation of substrate binding to the enzyme. 4. By use of enzyme inhibitors, tyrosine has been implicated as a functional residue at the active site of the enzyme. 5. The enzyme shows a fairly high degree of specificity towards its substrates."}
{"id": "PMID:19191", "title": "Evidence that 'inactive' renin is produced outside the kidney of the rat.", "content": "1. Inactive renin, which can be converted into an active form by acidification to pH 3-3, represents 4-63% of the total renin in rat peripheral plasma. 2. No inactive component could be found in the blood-free venous effluent of the perfused rat kidney before and after stimulation with isoprenaline. 3. This suggests a possible extrarenal source for inactive renin and may explain the presence of this component in anephric patients.", "contents": "Evidence that 'inactive' renin is produced outside the kidney of the rat. 1. Inactive renin, which can be converted into an active form by acidification to pH 3-3, represents 4-63% of the total renin in rat peripheral plasma. 2. No inactive component could be found in the blood-free venous effluent of the perfused rat kidney before and after stimulation with isoprenaline. 3. This suggests a possible extrarenal source for inactive renin and may explain the presence of this component in anephric patients."}
{"id": "PMID:19200", "title": "Studies of neurotransmitter release in the pathogenesis of hypertension.", "content": "Studies using a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nervous system in essential hypertension. Methodology which allows the study of local sympathetic turnover in CNS nuclei and peripheral blood vessels is described. This approach has been used to study the non-innervated sympathetic turnover phaeochromocytoma. It is suggested that studies of local regulatory mechanism in neurotransmitter release are required to give a greater understanding of the central and peripheral role of the sympathetic nervous system in the pathogenesis of hypertension.", "contents": "Studies of neurotransmitter release in the pathogenesis of hypertension. Studies using a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nervous system in essential hypertension. Methodology which allows the study of local sympathetic turnover in CNS nuclei and peripheral blood vessels is described. This approach has been used to study the non-innervated sympathetic turnover phaeochromocytoma. It is suggested that studies of local regulatory mechanism in neurotransmitter release are required to give a greater understanding of the central and peripheral role of the sympathetic nervous system in the pathogenesis of hypertension."}
{"id": "PMID:19202", "title": "Hypothalamic action of adrenoreceptor blocking agents.", "content": "In cats anaesthetized with pentobarbital sodium, the posterior hypothalamus was superfused and electrically stimulated with a push-pull cannula. The pressor response to stimulation of this hypothalamic area was inhibited when the hypothalamus was superfused with drugs blocking either alpha-adrenoreceptors (piperoxan, tolazoline), or beta-adrenoreceptors--(+/-)-propranolol, (-)-propranolol, practolol, sotalol, metoprolol. (+)-Propranolol and a concentration of procaine equianaesthetic to propranolol were ineffective. During superfusion with tolazoline in the presence of practolol the inhibition was twice as that when the hypothalamus was superfused with either tolazoline or practolol. In another series of experiments the push-pull cannula was inserted into the anterior hypothalamus. The depressor response to stimulation of this area was inhibited by the hypothalamic superfusion with the alpha-adrenoreceptor blocking drugs phentolamine, tolazoline, piperoxan or yohimbine. Hypothalamic superfusion with phenylephrine abolished the inhibitory effect of phentolamine on the depressor response. The results indicate that adrenoreceptors are present in the hypothalamus and that they are involved in blood pressure changes elicited by hypothalamic stimulation.", "contents": "Hypothalamic action of adrenoreceptor blocking agents. In cats anaesthetized with pentobarbital sodium, the posterior hypothalamus was superfused and electrically stimulated with a push-pull cannula. The pressor response to stimulation of this hypothalamic area was inhibited when the hypothalamus was superfused with drugs blocking either alpha-adrenoreceptors (piperoxan, tolazoline), or beta-adrenoreceptors--(+/-)-propranolol, (-)-propranolol, practolol, sotalol, metoprolol. (+)-Propranolol and a concentration of procaine equianaesthetic to propranolol were ineffective. During superfusion with tolazoline in the presence of practolol the inhibition was twice as that when the hypothalamus was superfused with either tolazoline or practolol. In another series of experiments the push-pull cannula was inserted into the anterior hypothalamus. The depressor response to stimulation of this area was inhibited by the hypothalamic superfusion with the alpha-adrenoreceptor blocking drugs phentolamine, tolazoline, piperoxan or yohimbine. Hypothalamic superfusion with phenylephrine abolished the inhibitory effect of phentolamine on the depressor response. The results indicate that adrenoreceptors are present in the hypothalamus and that they are involved in blood pressure changes elicited by hypothalamic stimulation."}
{"id": "PMID:19203", "title": "Catecholamines, cyclic AMP and renin in two contrasting forms of essential hypertension.", "content": "Essential hypertension (EH) can be subdivided according to the sympathetic and renin activity into two contrasting forms: (1) borderline beta-hyperadrenergic renin hyperresponsive and (2) stable beta-hypoadrenergic renin hyporesponsive EH. These two forms probably represent two expreme poles in the spectrum of EH in which sympathetic and renin hyper- or hyporeactivity cannot be accounted for by catecholamine determinations solely. beta-Adrenergic responsiveness monitored by plasma cyclic AMP determinations revealed plasma cyclic AMP, renin and circulatory hyperresponsiveness to isoproterenol in borderline hyperadrenergic EH while the opposite, cyclic AMP and renin hyporesponsiveness to insulin-induced hypoglycemia have been described in low renin stable EH. The kidney is in the center of the adrenergic abnormality in the two forms of EH with the borderline one excreting into the urine catecholamines not accounted for by their glomerular filtration. Catecholamines solely, however, do not account for the differences in both forms of EH which can probably be attributed to their different beta-adrenergic responsiveness.", "contents": "Catecholamines, cyclic AMP and renin in two contrasting forms of essential hypertension. Essential hypertension (EH) can be subdivided according to the sympathetic and renin activity into two contrasting forms: (1) borderline beta-hyperadrenergic renin hyperresponsive and (2) stable beta-hypoadrenergic renin hyporesponsive EH. These two forms probably represent two expreme poles in the spectrum of EH in which sympathetic and renin hyper- or hyporeactivity cannot be accounted for by catecholamine determinations solely. beta-Adrenergic responsiveness monitored by plasma cyclic AMP determinations revealed plasma cyclic AMP, renin and circulatory hyperresponsiveness to isoproterenol in borderline hyperadrenergic EH while the opposite, cyclic AMP and renin hyporesponsiveness to insulin-induced hypoglycemia have been described in low renin stable EH. The kidney is in the center of the adrenergic abnormality in the two forms of EH with the borderline one excreting into the urine catecholamines not accounted for by their glomerular filtration. Catecholamines solely, however, do not account for the differences in both forms of EH which can probably be attributed to their different beta-adrenergic responsiveness."}
{"id": "PMID:19206", "title": "Suppression of reactions to certain cosmetics.", "content": "Reactions to hair dyes and bleaches may be \"suppressed\" with corticosteroids and antihistamines. Reactions to nail polish may be prevented by a \"drying\" or \"polymerizing\" technique. Sensitization to certain perfume ingredients may be inhibited by a \"quenching\" phenomenon.", "contents": "Suppression of reactions to certain cosmetics. Reactions to hair dyes and bleaches may be \"suppressed\" with corticosteroids and antihistamines. Reactions to nail polish may be prevented by a \"drying\" or \"polymerizing\" technique. Sensitization to certain perfume ingredients may be inhibited by a \"quenching\" phenomenon."}
{"id": "PMID:19208", "title": "Arteriosclerotic aneurysm of the coronary artery.", "content": "The findings in a patient with an angiographically proven aneurysm of the coronary artery are described. The case is reviewed in the light of 115 similar cases reported in the literature. The patient had had numerous episodes of variant angina, a feature not previously described in coronary arterial aneurysms, which may be related to embolic showers originating from the aneurysm.", "contents": "Arteriosclerotic aneurysm of the coronary artery. The findings in a patient with an angiographically proven aneurysm of the coronary artery are described. The case is reviewed in the light of 115 similar cases reported in the literature. The patient had had numerous episodes of variant angina, a feature not previously described in coronary arterial aneurysms, which may be related to embolic showers originating from the aneurysm."}
{"id": "PMID:19205", "title": "Treatment of rheumatoid arthritis with tolmetin: a comparison with alclofenac.", "content": "A double-blind between-patient trial over 6 weeks to compare the effects of 1.6 g tolmetin daily with 4 g alclofenac daily was completed by 37 out of 44 out-patients with rheumatoid arthritis. Tolmetin proved as effective as alclofenac in relieving pain and in reducing both the articular index score and the number of inflamed joints. However, alclofenac produced a significantly greater reduction in the duration of morning stiffness, which could have been related to the timing of the initial daily dose of tolmetin. Onset of fatigue was significantly improved by both drugs. Neither treatment group exhibited any significant changes in the serum levels of IgG, IgA, and IgM, nor in the latex and sheep-cell agglutination titres. Although neither drug gave rise to serious side-effects, 3 patients (2 on tolmetin, 1 on alclofenac) were withdrawn because of skin rash, 2 (on tolmetin) because of gastro-intestinal upsets, and 1 from each group because of lack of analgesic effects.", "contents": "Treatment of rheumatoid arthritis with tolmetin: a comparison with alclofenac. A double-blind between-patient trial over 6 weeks to compare the effects of 1.6 g tolmetin daily with 4 g alclofenac daily was completed by 37 out of 44 out-patients with rheumatoid arthritis. Tolmetin proved as effective as alclofenac in relieving pain and in reducing both the articular index score and the number of inflamed joints. However, alclofenac produced a significantly greater reduction in the duration of morning stiffness, which could have been related to the timing of the initial daily dose of tolmetin. Onset of fatigue was significantly improved by both drugs. Neither treatment group exhibited any significant changes in the serum levels of IgG, IgA, and IgM, nor in the latex and sheep-cell agglutination titres. Although neither drug gave rise to serious side-effects, 3 patients (2 on tolmetin, 1 on alclofenac) were withdrawn because of skin rash, 2 (on tolmetin) because of gastro-intestinal upsets, and 1 from each group because of lack of analgesic effects."}
{"id": "PMID:19211", "title": "Metabolism and disposition of l-alpha-acetylmethadol in the rat.", "content": "The metabolism and disposition of the long-acting narcotic analygesic l-alpha-acetylmethadol (LAAM) were studied in the rat. 3H-LAAM was administered to male and female rats at doses of 5 mg/kg po and iv, and 10 mg/kg po. LAAM was rapidly absorbed and extensively metabolized. Five metabolites-noracetylmethadol, dinoracetylmethadol, methadol, normethadol, and N-acetylnormethadol-were identified in plasma and urine. Feces were the major route of elimination for the parent drug and metabolites. Less than 20% of the administered dose was excreted in the urine and, of this, greater than 90% was in the form of conjugates or polar metabolites. There is an apparent sex-related difference in LAAM disposition in the rat. LAAM and metabolites tended to persist in higher levels in female rats as compared with male rats. Similarly, male rats tended to excrete the drug at a faster rate than did females.", "contents": "Metabolism and disposition of l-alpha-acetylmethadol in the rat. The metabolism and disposition of the long-acting narcotic analygesic l-alpha-acetylmethadol (LAAM) were studied in the rat. 3H-LAAM was administered to male and female rats at doses of 5 mg/kg po and iv, and 10 mg/kg po. LAAM was rapidly absorbed and extensively metabolized. Five metabolites-noracetylmethadol, dinoracetylmethadol, methadol, normethadol, and N-acetylnormethadol-were identified in plasma and urine. Feces were the major route of elimination for the parent drug and metabolites. Less than 20% of the administered dose was excreted in the urine and, of this, greater than 90% was in the form of conjugates or polar metabolites. There is an apparent sex-related difference in LAAM disposition in the rat. LAAM and metabolites tended to persist in higher levels in female rats as compared with male rats. Similarly, male rats tended to excrete the drug at a faster rate than did females."}
{"id": "PMID:19212", "title": "The metabolism of p-methoxyamphetamine in dog and monkey. O-demethylation as a major route.", "content": "p-Hydroxyamphetamine (PHA) and p-hydroxybenzoic acid (PHBA) have been isolated by gas-liquid chromatography (GC) as urinary metabolites of p-methoxyamphetamine (PMA) in dogs and rhesus monkeys. The amounts of PMA excreted unchanged in the total 24-hr urine samples in dogs and monkeys were 26% and 3%, respectively, of the total administered doses. The amounts of the pharmacologically active metabolite PHA excreted in 24-hr urine samples were 13% in the dog and 44% in the monkey. In the dog, 72% of the PHA was present as free (unconjugated) PHA, whereas in the monkey the amount of PHA present in the free form was only 14%.", "contents": "The metabolism of p-methoxyamphetamine in dog and monkey. O-demethylation as a major route. p-Hydroxyamphetamine (PHA) and p-hydroxybenzoic acid (PHBA) have been isolated by gas-liquid chromatography (GC) as urinary metabolites of p-methoxyamphetamine (PMA) in dogs and rhesus monkeys. The amounts of PMA excreted unchanged in the total 24-hr urine samples in dogs and monkeys were 26% and 3%, respectively, of the total administered doses. The amounts of the pharmacologically active metabolite PHA excreted in 24-hr urine samples were 13% in the dog and 44% in the monkey. In the dog, 72% of the PHA was present as free (unconjugated) PHA, whereas in the monkey the amount of PHA present in the free form was only 14%."}
{"id": "PMID:19213", "title": "Determination of optically active thiopental, thiamylal, and their metabolites in human urine.", "content": "Methods involving solvent extraction and gas-liquid chromatography have been developed for quantitative determination of certain thiobarbiturates and their major metabolites in urine. The structures of the metabolites identified were confirmed by the use of gas chromatography/mass spectrometry and 13C-nuclear magnetic resonance spectroscopy. The present analytic methods were applied to the quantitative determination of (R)-(+)- and (S)-(-)-thiopental as well as (R)-(+)- and (S)-(-)-thiamylal and their major metabolites excreted in human urine. Minor metabolites were isolated and identified.", "contents": "Determination of optically active thiopental, thiamylal, and their metabolites in human urine. Methods involving solvent extraction and gas-liquid chromatography have been developed for quantitative determination of certain thiobarbiturates and their major metabolites in urine. The structures of the metabolites identified were confirmed by the use of gas chromatography/mass spectrometry and 13C-nuclear magnetic resonance spectroscopy. The present analytic methods were applied to the quantitative determination of (R)-(+)- and (S)-(-)-thiopental as well as (R)-(+)- and (S)-(-)-thiamylal and their major metabolites excreted in human urine. Minor metabolites were isolated and identified."}
{"id": "PMID:19214", "title": "The interrelationship between the metabolism of (S)-continine-N-oxide and (S)-cotinine.", "content": "The metabolism of (S)-cotinine-N-oxide was studied in the rabbit and the dog. The pattern of Koenig-positive substances in the urine of the animals suggested the presence of cotinine, demethylcotinine, hydroxycotinine, and allohydroxycotinine, compounds already previously identified as metabolites of (S)-cotinine and (S)-nicotine in many mammalian species. In the dog, 34% of the administered oral dose of (S)-cotinine-N-oxide was recovered from the urine, and 21% was recovered from the urine of the rabbit. Confirmation of the presence of (S)-cotinine, (S)-demethulcotinine, hydroxycotinine, and allohydroxycotinine in the urine of the rabbits was obtained by isolation of the metabolites as themselves of as derivatives. The data, although establishing the possibilities of an intermediary role for (S)-cotinine-N-oxide in the metabolism of nicotine, do not clearly indicate whether the metabolites such as demethylcotinine arise via the route (S)-cotinine-N-oxide leads to (S)-cotinine leads to (S)-demethylcotinine or via the alternate route (S)-cotinine-N-oxide leads to (S)-demethylcotinine-N-oxide leads to (S)-demethylcotinine.", "contents": "The interrelationship between the metabolism of (S)-continine-N-oxide and (S)-cotinine. The metabolism of (S)-cotinine-N-oxide was studied in the rabbit and the dog. The pattern of Koenig-positive substances in the urine of the animals suggested the presence of cotinine, demethylcotinine, hydroxycotinine, and allohydroxycotinine, compounds already previously identified as metabolites of (S)-cotinine and (S)-nicotine in many mammalian species. In the dog, 34% of the administered oral dose of (S)-cotinine-N-oxide was recovered from the urine, and 21% was recovered from the urine of the rabbit. Confirmation of the presence of (S)-cotinine, (S)-demethulcotinine, hydroxycotinine, and allohydroxycotinine in the urine of the rabbits was obtained by isolation of the metabolites as themselves of as derivatives. The data, although establishing the possibilities of an intermediary role for (S)-cotinine-N-oxide in the metabolism of nicotine, do not clearly indicate whether the metabolites such as demethylcotinine arise via the route (S)-cotinine-N-oxide leads to (S)-cotinine leads to (S)-demethylcotinine or via the alternate route (S)-cotinine-N-oxide leads to (S)-demethylcotinine-N-oxide leads to (S)-demethylcotinine."}
{"id": "PMID:19215", "title": "The metabolism of styrene oxide in the isolated perfused rat liver. Identification and quantitation of major metabolites.", "content": "Isolated perfused rat livers rapidly metabolized 14C-styrene oxide. A large proportion of the administered radioactivity was excreted in the bile as a single compound that was identified as S-(1-phenyl-2-hydroxyethyl)glutathione by comparison with an authentic synthetic standard. The circulating perfusate was found to contain approximately equal amounts of styrene glycol, mandelic acid, and the glutathione derivative.", "contents": "The metabolism of styrene oxide in the isolated perfused rat liver. Identification and quantitation of major metabolites. Isolated perfused rat livers rapidly metabolized 14C-styrene oxide. A large proportion of the administered radioactivity was excreted in the bile as a single compound that was identified as S-(1-phenyl-2-hydroxyethyl)glutathione by comparison with an authentic synthetic standard. The circulating perfusate was found to contain approximately equal amounts of styrene glycol, mandelic acid, and the glutathione derivative."}
{"id": "PMID:19216", "title": "Biliary excretion of iopanoate glucuronide by the rat.", "content": "Biliary excretion, plasma decay, and tissue distribution of 125I after a single intravenous dose (13 mumol/kg)  of 125I-Iopanoate and 125I-iopanoate glucuronide were compared in control and phenobarbital-pretreated rats under either anesthesia. In control animals the plasma decay of iopanoate glucuronide following iopanoate glucuronide administration was significantly greater than that after iopanoate administration. Biliary clearance following iopanoate glucuronide was approximately 20 times greater than that after iopanoate; within 60 min, 82% of the dose of iopanoate glucuronide, compared to 23% of the dose of iopanoate, was recovered in bile. Phenobarbital pretreatment significantly increased the biliary excretion following iopanoate administration but had no effect on that following iopanoate glucuronide. The urinary excretion after both agents was less than 3% of the administered dose within the 60-min experimental period. The data suggest that intracellular metabolism and/or binding may account for the marked difference in the biliary excretion of iopanoate glucuronide following iopanoate as compared to that after administration of iopanoate glucuronide.", "contents": "Biliary excretion of iopanoate glucuronide by the rat. Biliary excretion, plasma decay, and tissue distribution of 125I after a single intravenous dose (13 mumol/kg)  of 125I-Iopanoate and 125I-iopanoate glucuronide were compared in control and phenobarbital-pretreated rats under either anesthesia. In control animals the plasma decay of iopanoate glucuronide following iopanoate glucuronide administration was significantly greater than that after iopanoate administration. Biliary clearance following iopanoate glucuronide was approximately 20 times greater than that after iopanoate; within 60 min, 82% of the dose of iopanoate glucuronide, compared to 23% of the dose of iopanoate, was recovered in bile. Phenobarbital pretreatment significantly increased the biliary excretion following iopanoate administration but had no effect on that following iopanoate glucuronide. The urinary excretion after both agents was less than 3% of the administered dose within the 60-min experimental period. The data suggest that intracellular metabolism and/or binding may account for the marked difference in the biliary excretion of iopanoate glucuronide following iopanoate as compared to that after administration of iopanoate glucuronide."}
{"id": "PMID:19218", "title": "A preliminary pharmacokinetic model for several chlorinated biphenyls in the rat.", "content": "A mathematical model is presented to describe the kinetics of distribution, metabolism, and excretion of 4-chloro-, 4,4'-dichloro-, 2,2',4,5,5'-pentachloro-, and 2,2',4,4',5,5'-hexachlorobiphenyl in rats given an intravenols dose of 0.6 mg/kg. A modified flow-limited model simulates the penta- and hexachlorobiphenyl data for periods up to 96 hr but underestimates the mono- and dichlorobiphenyl data beyond 48 hr. The rate constant for metabolism by the liver decreases as degree of chlorination increases such that the rate constant is 200 times smaller for the hexachlorobiphenyl than for the monochlorobiphenyl. The value of the biliary clearance of metabolites is nearly the same for each chlorinated biphenyl, whereas the value of the urinary clearance decreases with increasing degree of chlorination, being 10 times smaller for hexachlorobiphenyl than for monochlorophenyl. The distribution coefficients between most tissues and blood are larger for each parent compound than for its metabolites. Hexachlorobiphenyl has the largest distribution coefficient of all the chlorinated biphenyls in each tissue, whereas the mono-, di-, and pentachlorobiphenyls show no consistent variation. For each compound the distribution coefficient is greater in the fat than in any other tissue. Changes in the fat volume of the growing rats were incorporated into the model in order to simulate the hexachlorobiphenyl concentrations in blood and fat for 42 days.", "contents": "A preliminary pharmacokinetic model for several chlorinated biphenyls in the rat. A mathematical model is presented to describe the kinetics of distribution, metabolism, and excretion of 4-chloro-, 4,4'-dichloro-, 2,2',4,5,5'-pentachloro-, and 2,2',4,4',5,5'-hexachlorobiphenyl in rats given an intravenols dose of 0.6 mg/kg. A modified flow-limited model simulates the penta- and hexachlorobiphenyl data for periods up to 96 hr but underestimates the mono- and dichlorobiphenyl data beyond 48 hr. The rate constant for metabolism by the liver decreases as degree of chlorination increases such that the rate constant is 200 times smaller for the hexachlorobiphenyl than for the monochlorobiphenyl. The value of the biliary clearance of metabolites is nearly the same for each chlorinated biphenyl, whereas the value of the urinary clearance decreases with increasing degree of chlorination, being 10 times smaller for hexachlorobiphenyl than for monochlorophenyl. The distribution coefficients between most tissues and blood are larger for each parent compound than for its metabolites. Hexachlorobiphenyl has the largest distribution coefficient of all the chlorinated biphenyls in each tissue, whereas the mono-, di-, and pentachlorobiphenyls show no consistent variation. For each compound the distribution coefficient is greater in the fat than in any other tissue. Changes in the fat volume of the growing rats were incorporated into the model in order to simulate the hexachlorobiphenyl concentrations in blood and fat for 42 days."}
{"id": "PMID:19219", "title": "Studies on the glucuronidation of 7-hydroxychlorpromazine in vitro.", "content": "The glucuronide of 7-hydroxychlorpromazine (CPOH), formed by incubation with hepatic microsomes and UDP-[U-14C]glucuronic acid, was isolated by extraction into 1-butanol at pH 1 and assayed by liquid scintillation counting. Although concentrations of CPOH greater than 3 X 10(-4) M stimulated its conjugation, the apparent KM of the transferase in microsomes from guinea pig liver for CPOH was 9.5 X 10(-5) M. The apparent activation of glucuronyltransferase by high concentrations of CPOH was prevented when preparations were maximmally stimulated by Triton X-100. The rate of conjugation of CPOH by preparations of guinea pig liver was almost twice that measured with those of rat liver. However, the maximal stimulation of the conjugation of CPOH by Triton with preparations of rat liver was almost twice that observed with microsomes from guinea pig liver. The conjugation of CPOH by microsomes from rat and guinea pig liver was inhibited about 25% by SKF 525-A (1 X 10(-4) M). The inhibitory action of SKF 525-A decreased at concentrations greater than 5 X 10(-4) M and no inhibition was observed at 1 X 10(-3) M.", "contents": "Studies on the glucuronidation of 7-hydroxychlorpromazine in vitro. The glucuronide of 7-hydroxychlorpromazine (CPOH), formed by incubation with hepatic microsomes and UDP-[U-14C]glucuronic acid, was isolated by extraction into 1-butanol at pH 1 and assayed by liquid scintillation counting. Although concentrations of CPOH greater than 3 X 10(-4) M stimulated its conjugation, the apparent KM of the transferase in microsomes from guinea pig liver for CPOH was 9.5 X 10(-5) M. The apparent activation of glucuronyltransferase by high concentrations of CPOH was prevented when preparations were maximmally stimulated by Triton X-100. The rate of conjugation of CPOH by preparations of guinea pig liver was almost twice that measured with those of rat liver. However, the maximal stimulation of the conjugation of CPOH by Triton with preparations of rat liver was almost twice that observed with microsomes from guinea pig liver. The conjugation of CPOH by microsomes from rat and guinea pig liver was inhibited about 25% by SKF 525-A (1 X 10(-4) M). The inhibitory action of SKF 525-A decreased at concentrations greater than 5 X 10(-4) M and no inhibition was observed at 1 X 10(-3) M."}
{"id": "PMID:19220", "title": "Effect of experimental diabetes on drug metabolism in the rat.", "content": "The effect of experimental diabetes on hepatic drug metabolism was studied in male Holtzman rats. Treatment of animals with streptozotocin and 6-aminonicotinamide, both agents which produce an insulin-deficient animal, caused prolongation of hexobarbital sleeping times and inhibition of the rate of metabolism of both hexobarbital and, to a lesser extent, aniline in vitro. Treatment of animals with N-methylacetamide, a diabetogen which does not cause insulin deficiency in the animal but rather produces an insulin-resistant state, did not affect the metabolism in vitro of either hexobarbital or aniline. Neither insulin nor any of the diabetogenic agents had any direct effect on drug metabolism in vitro. Furthermore, hepatic microsomal protein and cytochrome P-450 contents were not significantly different in any of the diabetic animals from those of the control animals. Hyperglycemia produced by glucose infusion did not affect the metabolism of hexobarbital in vitro. The effects of streptozotocin and 6-aminonicotinamide appeared to be at least partially due to the presence of an inhibitor in the liver cytosol which correlated with elevated hepatic cyclic AMP concentrations.", "contents": "Effect of experimental diabetes on drug metabolism in the rat. The effect of experimental diabetes on hepatic drug metabolism was studied in male Holtzman rats. Treatment of animals with streptozotocin and 6-aminonicotinamide, both agents which produce an insulin-deficient animal, caused prolongation of hexobarbital sleeping times and inhibition of the rate of metabolism of both hexobarbital and, to a lesser extent, aniline in vitro. Treatment of animals with N-methylacetamide, a diabetogen which does not cause insulin deficiency in the animal but rather produces an insulin-resistant state, did not affect the metabolism in vitro of either hexobarbital or aniline. Neither insulin nor any of the diabetogenic agents had any direct effect on drug metabolism in vitro. Furthermore, hepatic microsomal protein and cytochrome P-450 contents were not significantly different in any of the diabetic animals from those of the control animals. Hyperglycemia produced by glucose infusion did not affect the metabolism of hexobarbital in vitro. The effects of streptozotocin and 6-aminonicotinamide appeared to be at least partially due to the presence of an inhibitor in the liver cytosol which correlated with elevated hepatic cyclic AMP concentrations."}
{"id": "PMID:19227", "title": "[The effect of various front tooth filling materials on the in vitro growth of Streptococcus mutans].", "content": "While silicate cement inhibits bacterial growth, resin materials promote it immediately after mixing. Toxic tissue reactions may be induced by bacterial plaque accumulation. Our testing method complements existing in-vitro tests for recording chemo-toxic activities.", "contents": "[The effect of various front tooth filling materials on the in vitro growth of Streptococcus mutans]. While silicate cement inhibits bacterial growth, resin materials promote it immediately after mixing. Toxic tissue reactions may be induced by bacterial plaque accumulation. Our testing method complements existing in-vitro tests for recording chemo-toxic activities."}
{"id": "PMID:19228", "title": "[Effect of beta-adrenergic blockaders on the uterine musculature of rats].", "content": "The authors carried out a study on beta-adrenergic blockers Proprafnolol, Pindolol and Practolol, on an isolated uterus of a rat, obtained at various phases oestrus. The Beta-adrenergic blocker Pindolol manifested inhibiting effect on the spontaneous contractility of the uterus more marked after elevated level of gestagens. The pharmacological analysis gave foundation to the authors to assume that the relaxation of Pindolol was due to direct myotropic action. Propranolol in large doses and at high gestagenic level manifested antioxytocic activity. Practolol did not affect both spontaneous uterine activity as oxytoxin contraction.", "contents": "[Effect of beta-adrenergic blockaders on the uterine musculature of rats]. The authors carried out a study on beta-adrenergic blockers Proprafnolol, Pindolol and Practolol, on an isolated uterus of a rat, obtained at various phases oestrus. The Beta-adrenergic blocker Pindolol manifested inhibiting effect on the spontaneous contractility of the uterus more marked after elevated level of gestagens. The pharmacological analysis gave foundation to the authors to assume that the relaxation of Pindolol was due to direct myotropic action. Propranolol in large doses and at high gestagenic level manifested antioxytocic activity. Practolol did not affect both spontaneous uterine activity as oxytoxin contraction."}
{"id": "PMID:19229", "title": "[EEG-restitution and brain metabolism during electroconvulsive treatment in relaxation (author's transl)].", "content": "Blood-gas (pO2, pCO2) and pH-changes of venous (v.jugularis interna) and arterial (A.femoralis) blood samples, furthermore glucose utilization and lactate-, pyruvate-production of brain were investigated during electroconvulsive treatment in relaxation of 45 psychotic patients. The blood-gas values and substrate concentrations were statistically evaluated and represented in a function of the characteristic phases of the postconvulsive EEG-activity. A correlation was found between the glucose metabolism of the brain and the postconvulsive recovery of EEG. The restitution of postconvulsive brain metabolism runs discontinuously in the first 12 minutes of postconvulsive state. In the phase of electric silence and periodic delta-waves the brain metabolism was shifted to anaerobic direction. During the treatment no anoxic anoxia or acidosis takes place during the seizure activity and restitution, the measurable metabolic changes are moderate and supposedly play no important role in the \"effect\" of treatment.", "contents": "[EEG-restitution and brain metabolism during electroconvulsive treatment in relaxation (author's transl)]. Blood-gas (pO2, pCO2) and pH-changes of venous (v.jugularis interna) and arterial (A.femoralis) blood samples, furthermore glucose utilization and lactate-, pyruvate-production of brain were investigated during electroconvulsive treatment in relaxation of 45 psychotic patients. The blood-gas values and substrate concentrations were statistically evaluated and represented in a function of the characteristic phases of the postconvulsive EEG-activity. A correlation was found between the glucose metabolism of the brain and the postconvulsive recovery of EEG. The restitution of postconvulsive brain metabolism runs discontinuously in the first 12 minutes of postconvulsive state. In the phase of electric silence and periodic delta-waves the brain metabolism was shifted to anaerobic direction. During the treatment no anoxic anoxia or acidosis takes place during the seizure activity and restitution, the measurable metabolic changes are moderate and supposedly play no important role in the \"effect\" of treatment."}
{"id": "PMID:19230", "title": "[Comparative study using double-blind method of sultopride and thioproperazine].", "content": "This report includes a statistical analysis of the results of a double blind comparative study between sultopride and thioproperazine. Two rating scales were used: the standard B.P.R.S. and a simplified scale including 7 items: agitation--delusion--thought-disorganization--anxiety--aggressivity--hallucinations--autism. The comparison of the mean of the global scores obtained with the two rating scales shows a significant difference in activity in favour of sultopride. The analysis of the individual items shows regular modifications in favour of sultopride but these are not statistically significant. There are, also, no differences in the side-effects observed, particularly extra-pyramidal effects.", "contents": "[Comparative study using double-blind method of sultopride and thioproperazine]. This report includes a statistical analysis of the results of a double blind comparative study between sultopride and thioproperazine. Two rating scales were used: the standard B.P.R.S. and a simplified scale including 7 items: agitation--delusion--thought-disorganization--anxiety--aggressivity--hallucinations--autism. The comparison of the mean of the global scores obtained with the two rating scales shows a significant difference in activity in favour of sultopride. The analysis of the individual items shows regular modifications in favour of sultopride but these are not statistically significant. There are, also, no differences in the side-effects observed, particularly extra-pyramidal effects."}
{"id": "PMID:19231", "title": "[A new psychotropic drug: carpipramine, intermediate compound between 2 therapeutic classes].", "content": "An open clinical study was conducted with carpipramine in 100 hospitalized subjects presenting various mental disorders. The therapeutic results on symptoms were assessed both as a whole and with the help of a rating scale. Doses varied from 50 to 400 mg per day. Carpipramine seems to be particularly efficient on schizophrenias, 66 cases of which were tested. The best results were observed in hebephrenic forms and depressive syndroms during the illness; in these indications, carpipramine exerts a clear psychomotor stimulating activity which is useful in decreasing indifference, apathy and ideomotor slowness. Schizophrenias with paranoid delusions or depersonalization anxiety tend to be somehow aggravated. Carpipramine does not seem to be a true antidepressant despite its desinhibitory properties. The compound proves useful in deficits of the psychomotor tone such as those occuring in psychasthenia or the deficit syndrom which follows withdrawal from opiates. Clinical and biological tolerances seem to be excellent and extrapyramidal side effects are exceptional. Carpipramine may be considered as a strongly desinhibitory neuroleptic agent which bears some resemblance to antidepressants because of its psychoanaleptic effect. The authors raise the question of possible antipsychotic properties in higher doses in relation to pharmacological data and a bipolar, antipsychotic and predominantly desinhibitory, therapeutic action.", "contents": "[A new psychotropic drug: carpipramine, intermediate compound between 2 therapeutic classes]. An open clinical study was conducted with carpipramine in 100 hospitalized subjects presenting various mental disorders. The therapeutic results on symptoms were assessed both as a whole and with the help of a rating scale. Doses varied from 50 to 400 mg per day. Carpipramine seems to be particularly efficient on schizophrenias, 66 cases of which were tested. The best results were observed in hebephrenic forms and depressive syndroms during the illness; in these indications, carpipramine exerts a clear psychomotor stimulating activity which is useful in decreasing indifference, apathy and ideomotor slowness. Schizophrenias with paranoid delusions or depersonalization anxiety tend to be somehow aggravated. Carpipramine does not seem to be a true antidepressant despite its desinhibitory properties. The compound proves useful in deficits of the psychomotor tone such as those occuring in psychasthenia or the deficit syndrom which follows withdrawal from opiates. Clinical and biological tolerances seem to be excellent and extrapyramidal side effects are exceptional. Carpipramine may be considered as a strongly desinhibitory neuroleptic agent which bears some resemblance to antidepressants because of its psychoanaleptic effect. The authors raise the question of possible antipsychotic properties in higher doses in relation to pharmacological data and a bipolar, antipsychotic and predominantly desinhibitory, therapeutic action."}
{"id": "PMID:19232", "title": "[Psychosensorial manifestations observed in psychotic patients treated with betamimetic drugs].", "content": "We report four observations of women who had acute or subacute psychotic crisis and who were stabilized without any manifestation. In order to delay delivery these women received during pre-partum high doses of beta-mimetic drugs (isoxsuprine and salbutamol). Such a prescription seems to have been responsible of acute and transient psychotic symptoms similar to those observed in drug-induced psychosis (derealisation preceeding depersonalization, visual and auditory hallucinations, anxiety). Recently Gluckman has described a similar case to those reported here. But in his case the conditions of coming out were different and there was a lack of psychotic antecedents. Previous works concerning \"psychotic-like\" effects of beta-blokers rise the question of possible psychodysleptic effects of beta-mimetic drugs.", "contents": "[Psychosensorial manifestations observed in psychotic patients treated with betamimetic drugs]. We report four observations of women who had acute or subacute psychotic crisis and who were stabilized without any manifestation. In order to delay delivery these women received during pre-partum high doses of beta-mimetic drugs (isoxsuprine and salbutamol). Such a prescription seems to have been responsible of acute and transient psychotic symptoms similar to those observed in drug-induced psychosis (derealisation preceeding depersonalization, visual and auditory hallucinations, anxiety). Recently Gluckman has described a similar case to those reported here. But in his case the conditions of coming out were different and there was a lack of psychotic antecedents. Previous works concerning \"psychotic-like\" effects of beta-blokers rise the question of possible psychodysleptic effects of beta-mimetic drugs."}
{"id": "PMID:19233", "title": "Estradiol binding capacity in the cryptorchid rat testis.", "content": "Mature male Sprague-Dawley rats were made surgically cryptorchid at 47--50 days of age. Animals were sacrificed as controls and at 7, 14, and 21 days post-surgery. The testes were removed and utilized to determine the effects of cryptorchidism on tissue weight loss, histological changes, and cytoplasmic estradiol binding capacity. Testis weight decreased from a mean +/- SE of 1.1 +/- 0.09 to .41 +/- 0.02 g during the 21 day period, a 66% decrease in weight. Light microscopy revealed that the process of spermatogenesis was inhibited, the germinal epithelium had degenerated, and the tubules had become smaller in diameter. The interstitial tissue volume progressively increased through day 21 post-surgery. The cytoplasmic estradiol binding capacity, expressed as fmoles [3H]-estradiol/mg cytosol protein, increased markedly from a control of 16 +/- 1.1 to 36 +/- 8.0 at day 7 after surgery; this represented a 126% increase in binding capacity in one week. Binding capacity was equivalent to 54 +/- 7.4 and 58 +/- 10.5 fmol/mg on days 14 and 21 post-surgery, respectively. Testicular content of cytoplasmic estrogen receptors was shown to increase from 349 to a maximum of 575 fmoles/testis at day 7. Receptor content then declined slowly to a value of 481 at day 21. Testicular content of receptor is presumed to reflect an alteration in the Leydig cells induced by cryptorchidism.", "contents": "Estradiol binding capacity in the cryptorchid rat testis. Mature male Sprague-Dawley rats were made surgically cryptorchid at 47--50 days of age. Animals were sacrificed as controls and at 7, 14, and 21 days post-surgery. The testes were removed and utilized to determine the effects of cryptorchidism on tissue weight loss, histological changes, and cytoplasmic estradiol binding capacity. Testis weight decreased from a mean +/- SE of 1.1 +/- 0.09 to .41 +/- 0.02 g during the 21 day period, a 66% decrease in weight. Light microscopy revealed that the process of spermatogenesis was inhibited, the germinal epithelium had degenerated, and the tubules had become smaller in diameter. The interstitial tissue volume progressively increased through day 21 post-surgery. The cytoplasmic estradiol binding capacity, expressed as fmoles [3H]-estradiol/mg cytosol protein, increased markedly from a control of 16 +/- 1.1 to 36 +/- 8.0 at day 7 after surgery; this represented a 126% increase in binding capacity in one week. Binding capacity was equivalent to 54 +/- 7.4 and 58 +/- 10.5 fmol/mg on days 14 and 21 post-surgery, respectively. Testicular content of cytoplasmic estrogen receptors was shown to increase from 349 to a maximum of 575 fmoles/testis at day 7. Receptor content then declined slowly to a value of 481 at day 21. Testicular content of receptor is presumed to reflect an alteration in the Leydig cells induced by cryptorchidism."}
{"id": "PMID:19235", "title": "Possible role of calcium-dependent protein phosphorylation in mediating neurotransmitter release and anticonvulsant action.", "content": "The results demonstrate that calcium and phenytoin have antagonistic actions on the net level of endogenous phosphorylation of specific rat brain proteins. These specific phosphoproteins were shown to be present in synaptosome preparations, and evidence is presented for the localization of these phosphoproteins within the presynaptic nerve terminal. The data are compatible with the hypothesis that the antagonistic actions of calcium and phenytoin on the phosphorylation of synaptosome proteins may be the underlying molecular mechanism mediating the opposing actions of these agents on the release of neurotransmitter from the presynaptic nerve terminal.", "contents": "Possible role of calcium-dependent protein phosphorylation in mediating neurotransmitter release and anticonvulsant action. The results demonstrate that calcium and phenytoin have antagonistic actions on the net level of endogenous phosphorylation of specific rat brain proteins. These specific phosphoproteins were shown to be present in synaptosome preparations, and evidence is presented for the localization of these phosphoproteins within the presynaptic nerve terminal. The data are compatible with the hypothesis that the antagonistic actions of calcium and phenytoin on the phosphorylation of synaptosome proteins may be the underlying molecular mechanism mediating the opposing actions of these agents on the release of neurotransmitter from the presynaptic nerve terminal."}
{"id": "PMID:19236", "title": "gamma-Glutamyltranspeptidase activity in newborn rat kidney brush border.", "content": "gamma-Glutamyltranspeptidase, known to be localized in the proximal tubule cell brush border in the rat, is a membrane-bound enzyme which transfers the gamma-glutamyl moiety of glutathione or its analogue gamma-glutamyl-p-nitroanilide to an amino acid or dipeptide acceptor. Brush borders were isolated from the kidneys of newborn and adult Sprague-Dawley rats and assayed for gamma-glutamyltranspeptidase activity. There is an increase in specific activity in the brush border with maturation. Newborn and adult brush border preparations exhibit similar pH optima, substrate affinities, apparent Km values, patterns of heat inactivation, inhibition by glutathione, and migration on polyacrylamide gels. Polyacrylamide gel electrophoresis of a deoxycholate extract of brush border proteins and subsequent reaction with substrate within the gel reveal the presence of two bands, suggesting the presence of two forms of gamma-glutamyltranspeptidase in the rat kidney brush border.", "contents": "gamma-Glutamyltranspeptidase activity in newborn rat kidney brush border. gamma-Glutamyltranspeptidase, known to be localized in the proximal tubule cell brush border in the rat, is a membrane-bound enzyme which transfers the gamma-glutamyl moiety of glutathione or its analogue gamma-glutamyl-p-nitroanilide to an amino acid or dipeptide acceptor. Brush borders were isolated from the kidneys of newborn and adult Sprague-Dawley rats and assayed for gamma-glutamyltranspeptidase activity. There is an increase in specific activity in the brush border with maturation. Newborn and adult brush border preparations exhibit similar pH optima, substrate affinities, apparent Km values, patterns of heat inactivation, inhibition by glutathione, and migration on polyacrylamide gels. Polyacrylamide gel electrophoresis of a deoxycholate extract of brush border proteins and subsequent reaction with substrate within the gel reveal the presence of two bands, suggesting the presence of two forms of gamma-glutamyltranspeptidase in the rat kidney brush border."}
{"id": "PMID:19237", "title": "The optimum pH of renal adenosine triphosphatase and its variation with the type of ATP.", "content": "The in vitro optimum pH of renal (Na+, K+)-ATPase, assumed to be 7.8, depends on the type of ATP used. The accepted value is obtained with 'grade II' ATP but with purer ATP ('Sigma grade') it lies close to the intracellular pH in rat medulla and cortex (pH 7.0, 7.2). Values were identical in rats subjected to dietary potassium depletion for 2-4 weeks. The optimal Mg2+ concentration was also influenced by the type of ATP but Mg ATPase activity was unaffected. Both types of ATP were hydrolysed by trichloracetic acid. Where the purer ATP is used the assay conditions need to be modified accordingly.", "contents": "The optimum pH of renal adenosine triphosphatase and its variation with the type of ATP. The in vitro optimum pH of renal (Na+, K+)-ATPase, assumed to be 7.8, depends on the type of ATP used. The accepted value is obtained with 'grade II' ATP but with purer ATP ('Sigma grade') it lies close to the intracellular pH in rat medulla and cortex (pH 7.0, 7.2). Values were identical in rats subjected to dietary potassium depletion for 2-4 weeks. The optimal Mg2+ concentration was also influenced by the type of ATP but Mg ATPase activity was unaffected. Both types of ATP were hydrolysed by trichloracetic acid. Where the purer ATP is used the assay conditions need to be modified accordingly."}
{"id": "PMID:19238", "title": "Lack of hepatic enzymatic adaptation to low and high levels of dietary protein in the adult cat.", "content": "The activities of three urea cycle enzymes, several nitrogen catabolic, gluconeogenic, and lipogenic enzymes were measured in the liver of adult cats fed: a commercial kibble; a 17.5 or 70% protein purified diet, or starved for 5 days. Except for an increase in tyrosine transaminase (EC 2.6.1.5) after feeding the high protein diet, there were no changes in the activities of the hepatic enzymes as influenced by dietary protein level. Likewise, starvation had a minimal effect on the activities of these enzymes as compared to that found in similar experiments in rats. These results indicate that the cat may have only minimal capabilities for enzyme adaptation as compared to that found in many herbivores and omnivores and may provide an explanation as to why cats have an unusually high protein requirement as compared to many other mammals.", "contents": "Lack of hepatic enzymatic adaptation to low and high levels of dietary protein in the adult cat. The activities of three urea cycle enzymes, several nitrogen catabolic, gluconeogenic, and lipogenic enzymes were measured in the liver of adult cats fed: a commercial kibble; a 17.5 or 70% protein purified diet, or starved for 5 days. Except for an increase in tyrosine transaminase (EC 2.6.1.5) after feeding the high protein diet, there were no changes in the activities of the hepatic enzymes as influenced by dietary protein level. Likewise, starvation had a minimal effect on the activities of these enzymes as compared to that found in similar experiments in rats. These results indicate that the cat may have only minimal capabilities for enzyme adaptation as compared to that found in many herbivores and omnivores and may provide an explanation as to why cats have an unusually high protein requirement as compared to many other mammals."}
{"id": "PMID:19240", "title": "Dissociation of small-intestinal sucrase - isomaltase complex into enzymatically active subunits.", "content": "1. The sucrase - isomaltase complex from rabbit small intestine dissociated into its subunits upon reaction with citraconic anhydride. They can recombine after deacylation under mild acidic conditions. 2. When citraconylated, the subunits could be separated and isolated in a catalytically active form. 3. The previously reported procedure for separation of the subunits by alkaline treatment at pH 9.6 is apparently not due to contaminating degradative enzymes (possibly still present at undetectable levels in the isolated sucrase - isomaltase complex) but to the action of alkali.", "contents": "Dissociation of small-intestinal sucrase - isomaltase complex into enzymatically active subunits. 1. The sucrase - isomaltase complex from rabbit small intestine dissociated into its subunits upon reaction with citraconic anhydride. They can recombine after deacylation under mild acidic conditions. 2. When citraconylated, the subunits could be separated and isolated in a catalytically active form. 3. The previously reported procedure for separation of the subunits by alkaline treatment at pH 9.6 is apparently not due to contaminating degradative enzymes (possibly still present at undetectable levels in the isolated sucrase - isomaltase complex) but to the action of alkali."}
{"id": "PMID:19242", "title": "On the pH-dependence of the reaction of hemoglobin with carbon monoxide.", "content": "Flash-photolysis experiments were performed on solutions of carbonmonoxy hemoglobin (human Hb A) as function as pH. The fraction of fast reaction and the amount of photodissociation as produced by a given amount of light quanta has been analyzed in terms of the allosteric model of ligand binding by Monod, Wyman and Changeux. It is shown how the switch-over point of the allosteric transition from the T or R state is controlled by the protons, which act as allosteric effectors.", "contents": "On the pH-dependence of the reaction of hemoglobin with carbon monoxide. Flash-photolysis experiments were performed on solutions of carbonmonoxy hemoglobin (human Hb A) as function as pH. The fraction of fast reaction and the amount of photodissociation as produced by a given amount of light quanta has been analyzed in terms of the allosteric model of ligand binding by Monod, Wyman and Changeux. It is shown how the switch-over point of the allosteric transition from the T or R state is controlled by the protons, which act as allosteric effectors."}
{"id": "PMID:19243", "title": "The role of an essential histidine residue of yeast alcohol dehydrogenase.", "content": "1. Inactivation of yeast alcohol dehydrogenase for diethyl pyrocarbonate indicates that one histidine residue per enzyme subunit is necessary for enzymic activity. The inactivated enzyme regains its activity over a period of days. 2. Enzyme modified by diethyl pyrocarbonate can form the binary enzyme - NADH complex with the same maximum NADH-binding capacity as that of native enzyme. Modified enzyme cannot form normal ternary complexes of the type enzyme - NADH - acetamide and enzyme - NAD+ - pyrazole, which are characteristic of native enzyme. 3. The rate constant for the reaction of enzyme with diethyl pyrocarbonate has been determined over the pH range 5.5--9. The histidine residue involved has approximately the same pKa as free histidine, but is 10-fold more reactive than free histidine.", "contents": "The role of an essential histidine residue of yeast alcohol dehydrogenase. 1. Inactivation of yeast alcohol dehydrogenase for diethyl pyrocarbonate indicates that one histidine residue per enzyme subunit is necessary for enzymic activity. The inactivated enzyme regains its activity over a period of days. 2. Enzyme modified by diethyl pyrocarbonate can form the binary enzyme - NADH complex with the same maximum NADH-binding capacity as that of native enzyme. Modified enzyme cannot form normal ternary complexes of the type enzyme - NADH - acetamide and enzyme - NAD+ - pyrazole, which are characteristic of native enzyme. 3. The rate constant for the reaction of enzyme with diethyl pyrocarbonate has been determined over the pH range 5.5--9. The histidine residue involved has approximately the same pKa as free histidine, but is 10-fold more reactive than free histidine."}
{"id": "PMID:19244", "title": "The effect of macromolecular polyanions on the functional properties of human hemoglobin.", "content": "The binding of dextran sulphate and heparin to human hemoglobin and their effect on the properties of gas transport have been investigated. Both dextran sulphate and heparin are strongly bound by oxy-hemoglobin as well as deoxyhemoglobin and the stoichiometry of the binding (polyanion/tetrameric hemoglobin) is less than unity; sedimentation analysis gives indication for the existence of octomers. The oxygen affinity of hemoglobin is decreased, to the same extent, by both dextran sulphate and heparin. This effect is pH-dependent. In addition the polyanions affect the position and the magnitude of the Bohr effect. In the presence of dextran sulphate the recombination of hemoglobin with carbon monoxide after flash photolysis is biphasic and the fraction of quickly reacting material increases with dilution of the protein.", "contents": "The effect of macromolecular polyanions on the functional properties of human hemoglobin. The binding of dextran sulphate and heparin to human hemoglobin and their effect on the properties of gas transport have been investigated. Both dextran sulphate and heparin are strongly bound by oxy-hemoglobin as well as deoxyhemoglobin and the stoichiometry of the binding (polyanion/tetrameric hemoglobin) is less than unity; sedimentation analysis gives indication for the existence of octomers. The oxygen affinity of hemoglobin is decreased, to the same extent, by both dextran sulphate and heparin. This effect is pH-dependent. In addition the polyanions affect the position and the magnitude of the Bohr effect. In the presence of dextran sulphate the recombination of hemoglobin with carbon monoxide after flash photolysis is biphasic and the fraction of quickly reacting material increases with dilution of the protein."}
{"id": "PMID:19247", "title": "Nuclear-magnetic-resonance-spectroscopic studies of the amino groups of insulin.", "content": "The amino groups of insulin have been studied by 1H and 13C nuclear magnetic resonance spectroscopy in insulin, zinc-free insulin and methylated insulin. By difference spectroscopy it is possible to follow the shift with pH of the epsilon-CH2 and delta-CH2 proton resonances of lysine-B29 in insulin. In methylated insulin the dimethyl proton resonances of glycine-A1, phenylalanine-B1 and lysine-B29 can be followed as a function of pH. In native insulin pKapp values of 6.7 and 8.0 are obtained for phenylalanine-B1 and glycine-A1 (the assignment is tentative) and 11.2 for lysine-B29. Separate resonances have been observed from the lysine-B29 Nepsilon-(CH3)2 group for the monomeric and dimeric forms of methylated insulin, which indicates a small change in the environment of lysine-B29 on dimerisation. The nuclear magnetic resonance spectral characteristics of these groups are, in general, consistent with the overall structure of the crystal form of the 2-zinc insulin hexamer.", "contents": "Nuclear-magnetic-resonance-spectroscopic studies of the amino groups of insulin. The amino groups of insulin have been studied by 1H and 13C nuclear magnetic resonance spectroscopy in insulin, zinc-free insulin and methylated insulin. By difference spectroscopy it is possible to follow the shift with pH of the epsilon-CH2 and delta-CH2 proton resonances of lysine-B29 in insulin. In methylated insulin the dimethyl proton resonances of glycine-A1, phenylalanine-B1 and lysine-B29 can be followed as a function of pH. In native insulin pKapp values of 6.7 and 8.0 are obtained for phenylalanine-B1 and glycine-A1 (the assignment is tentative) and 11.2 for lysine-B29. Separate resonances have been observed from the lysine-B29 Nepsilon-(CH3)2 group for the monomeric and dimeric forms of methylated insulin, which indicates a small change in the environment of lysine-B29 on dimerisation. The nuclear magnetic resonance spectral characteristics of these groups are, in general, consistent with the overall structure of the crystal form of the 2-zinc insulin hexamer."}
{"id": "PMID:19249", "title": "Bacteriorhodopsin-mediated photophosphorylation in Halobacterium halobium.", "content": "The rate of halobacterial photophosphorylation was found to be a linear function of light intensity over a wide range (between 1 and 20 mW/cm2). At higher light intensities (above 25 mW/cm2) the ATP-synthesizing system itself limits the maximal rate of photophosphorylation. The optimal external pH range for this type of photophosphorylation is between pH 6.2 and 7.2 external. The photophosphorylation rate is directly proportional to the bacteriorhodopsin content of the cells. The quantum requirement for photophosphorylation was found to be 22 +/- 5 photons per ATP molecule synthesized. According to Mitchell's chemiosmotic hypothesis of energy coupling phosphorylation can be driven by a membrane potential or a pH gradient or a combination of both. From the results of experiments with drugs which abolish or reduce either one of the two components we conclude that the major driving force for photophosphorylation above an external pH value of 6.5 is the membrane potential, while at more acidic pH value the pH gradient becomes dominating. We did not observe a correlation between a transient alkalinization of the medium and ATP-synthesis upon illumination under certain conditions.", "contents": "Bacteriorhodopsin-mediated photophosphorylation in Halobacterium halobium. The rate of halobacterial photophosphorylation was found to be a linear function of light intensity over a wide range (between 1 and 20 mW/cm2). At higher light intensities (above 25 mW/cm2) the ATP-synthesizing system itself limits the maximal rate of photophosphorylation. The optimal external pH range for this type of photophosphorylation is between pH 6.2 and 7.2 external. The photophosphorylation rate is directly proportional to the bacteriorhodopsin content of the cells. The quantum requirement for photophosphorylation was found to be 22 +/- 5 photons per ATP molecule synthesized. According to Mitchell's chemiosmotic hypothesis of energy coupling phosphorylation can be driven by a membrane potential or a pH gradient or a combination of both. From the results of experiments with drugs which abolish or reduce either one of the two components we conclude that the major driving force for photophosphorylation above an external pH value of 6.5 is the membrane potential, while at more acidic pH value the pH gradient becomes dominating. We did not observe a correlation between a transient alkalinization of the medium and ATP-synthesis upon illumination under certain conditions."}
{"id": "PMID:19250", "title": "The effective proton conductance of the inner membrane of mitochondria from brown adipose tissue. Dependency on proton electrochemical potential gradient.", "content": "The nucleotide-sensitive H+ (OH-) conducting pathway of mitochondria from the brown-adipose tissue of cold-adapted guinea-pigs passes an effective proton current which is directly proportional to the proton electrochemical gradient. At 23 degrees C and pH 7.0 this conductance is 16 nmol H+ - min-1 - mg-1 - mV-1. Addition of 0.2 mM GDP results in a conductance which is linear and low (0.7 nmol H+ - min-1 - mg-1 - mV-1) until deltamicronH+ exceeds 220 mV. At higher values of deltamicronH+, which can be attained by glycerol 3-phosphate oxidation but not palmitoyl-L-carnitine plus malate oxidation, the membrane conductance greatly increases, effectively limiting the maximal deltamicronH+ to 240 mV. High glycerol 3-phosphate concentrations which have the thermodynamic potential to exceed this value of deltamicronH+ instead create a greatly increased rate of controlled respiration. The generality and significance of this device to limit deltamicronH+, and its relation to the nucleotide-sensitive conductance, are discussed.", "contents": "The effective proton conductance of the inner membrane of mitochondria from brown adipose tissue. Dependency on proton electrochemical potential gradient. The nucleotide-sensitive H+ (OH-) conducting pathway of mitochondria from the brown-adipose tissue of cold-adapted guinea-pigs passes an effective proton current which is directly proportional to the proton electrochemical gradient. At 23 degrees C and pH 7.0 this conductance is 16 nmol H+ - min-1 - mg-1 - mV-1. Addition of 0.2 mM GDP results in a conductance which is linear and low (0.7 nmol H+ - min-1 - mg-1 - mV-1) until deltamicronH+ exceeds 220 mV. At higher values of deltamicronH+, which can be attained by glycerol 3-phosphate oxidation but not palmitoyl-L-carnitine plus malate oxidation, the membrane conductance greatly increases, effectively limiting the maximal deltamicronH+ to 240 mV. High glycerol 3-phosphate concentrations which have the thermodynamic potential to exceed this value of deltamicronH+ instead create a greatly increased rate of controlled respiration. The generality and significance of this device to limit deltamicronH+, and its relation to the nucleotide-sensitive conductance, are discussed."}
{"id": "PMID:19253", "title": "alpha-D-galactosidase from soybeans destroying blood-group B antigens. Purification by affinity chromatography and properties.", "content": "alpha-D-Galactosidase was isolated from untoasted soybean meal and purified to homogeneity by affinity chromatography on N-epsilon-aminoacaproyl alpha-D-galactopyranosylamine-Sepharose. The purified enzyme destroyed the B-specificity of human ovarian cyst B-glycoprotein with an accompanying increase in H-specificity, and converted human type-B erythrocytes to type O. The enzyme consists primarily of a tetramer, molecular weight 150 000 +/- 5 000 at pH 4.0 and of a monomer, molecular weight 40 000 +/- 3 000 at pH 8.0. Polyacrylamide gel electrophoresis in dodecyl sulfate at pH 7.2 distinguished between two types of monomeric unit of similar molecular weight. N-terminal alanine was identified as the sole N-terminal amino acid residue. The enzyme was shown to be devoid of carbohydrate.", "contents": "alpha-D-galactosidase from soybeans destroying blood-group B antigens. Purification by affinity chromatography and properties. alpha-D-Galactosidase was isolated from untoasted soybean meal and purified to homogeneity by affinity chromatography on N-epsilon-aminoacaproyl alpha-D-galactopyranosylamine-Sepharose. The purified enzyme destroyed the B-specificity of human ovarian cyst B-glycoprotein with an accompanying increase in H-specificity, and converted human type-B erythrocytes to type O. The enzyme consists primarily of a tetramer, molecular weight 150 000 +/- 5 000 at pH 4.0 and of a monomer, molecular weight 40 000 +/- 3 000 at pH 8.0. Polyacrylamide gel electrophoresis in dodecyl sulfate at pH 7.2 distinguished between two types of monomeric unit of similar molecular weight. N-terminal alanine was identified as the sole N-terminal amino acid residue. The enzyme was shown to be devoid of carbohydrate."}
{"id": "PMID:19254", "title": "Ionization dependence of camphor binding and spin conversion of the complex between cytochrome P-450 and camphor. Kinetic and static studies at sub-zero temperatures.", "content": "The kinetic rate constants of formation and dissociation of the cytochrome-P-450 - camphor complex (Fe3+-RH) have been obtained by low-temperature (+ 5 degrees C to -20 degrees C) stopped-flow experiments. Simiarly the high-spin/low-spin equilibrium of this complex has been studied as a function of temperature and protonic activity. Both the camphor-binding mechanism and the high-spin/low-spin thermodynamic parameters of Fe3+-RH depend on the protonic activity of the medium in the physiological pH range. The binding rate constants are shown to depend on the ionization of a residue of the protein, probably a histidine. Linear enthalpy-entropy compensation is observed for the camphor binding as well as for the spin-state transition. A camphor-binding-induced change of the electrostatic potential is discussed.", "contents": "Ionization dependence of camphor binding and spin conversion of the complex between cytochrome P-450 and camphor. Kinetic and static studies at sub-zero temperatures. The kinetic rate constants of formation and dissociation of the cytochrome-P-450 - camphor complex (Fe3+-RH) have been obtained by low-temperature (+ 5 degrees C to -20 degrees C) stopped-flow experiments. Simiarly the high-spin/low-spin equilibrium of this complex has been studied as a function of temperature and protonic activity. Both the camphor-binding mechanism and the high-spin/low-spin thermodynamic parameters of Fe3+-RH depend on the protonic activity of the medium in the physiological pH range. The binding rate constants are shown to depend on the ionization of a residue of the protein, probably a histidine. Linear enthalpy-entropy compensation is observed for the camphor binding as well as for the spin-state transition. A camphor-binding-induced change of the electrostatic potential is discussed."}
{"id": "PMID:19257", "title": "Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions [beta6(A3)glutamic acid leads to valine and beta142 (h20) alanine leads to valine).", "content": "Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.", "contents": "Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions [beta6(A3)glutamic acid leads to valine and beta142 (h20) alanine leads to valine). Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis."}
{"id": "PMID:19260", "title": "Mechanism of oestrogen and progesterone effects on lipid and carbohydrate metabolism: alteration in the insulin: glucagon molar ratio and hepatic enzyme activity.", "content": "As in women receiving oestrogens the administration of 17beta-oestradiol to ovariectomized female rats caused a rise in fasting plasma triglycerides and a fall in plasma glucose. Progesterone, on the other hand, had no significant effects. In the oestradiol treated rats, the portal vein basal insulin levels were slightly reduced. Oestradiol, however, had a marked suppressive effect on the alpha cells of the pancreas resulting in a greater reduction in basal glucagon and impaired glucagon response to alanine infusions. The relative insulin to glucagon (I/G) molar concentration ratio in portal vein blood was increased. Oestradiol also produced a dose dependent increase in the activity of the liver lipogenic enzymes, acetyl CoA carboxylase and fatty acid synthetase. On the other hand, the activity of the gluconeogenic rate limiting enzyme phosphoenol-pyruvate carboxykinase (PEPCK) was inhibited. The cross-over pattern of gluconeogenic intermediates confirmed inhibition of gluconeogenesis at this step, an effect which is similar to that induced by relative insulin 'excess'. Progesterone produced an increase in the portal vein insulin concentrations. Both the basal and the alanine-stimulated glucagon levels were also increased. The I/G molar ratio in portal vein blood of progesterone treated rats remained unaltered and the hepatic lipogenic and gluconeogenic enzyme activities were similar to control animals. These data suggest that insulin activity is increased relative to glucagon in the liver of oestradiol-treated rats due to the rise in portal vein I/G ratio. The changes in liver lipogenic and gluconeogenic enzymes and the alterations in fasting plasma triglycerides and glucose in response to oestrogens could be secondary to this effect.", "contents": "Mechanism of oestrogen and progesterone effects on lipid and carbohydrate metabolism: alteration in the insulin: glucagon molar ratio and hepatic enzyme activity. As in women receiving oestrogens the administration of 17beta-oestradiol to ovariectomized female rats caused a rise in fasting plasma triglycerides and a fall in plasma glucose. Progesterone, on the other hand, had no significant effects. In the oestradiol treated rats, the portal vein basal insulin levels were slightly reduced. Oestradiol, however, had a marked suppressive effect on the alpha cells of the pancreas resulting in a greater reduction in basal glucagon and impaired glucagon response to alanine infusions. The relative insulin to glucagon (I/G) molar concentration ratio in portal vein blood was increased. Oestradiol also produced a dose dependent increase in the activity of the liver lipogenic enzymes, acetyl CoA carboxylase and fatty acid synthetase. On the other hand, the activity of the gluconeogenic rate limiting enzyme phosphoenol-pyruvate carboxykinase (PEPCK) was inhibited. The cross-over pattern of gluconeogenic intermediates confirmed inhibition of gluconeogenesis at this step, an effect which is similar to that induced by relative insulin 'excess'. Progesterone produced an increase in the portal vein insulin concentrations. Both the basal and the alanine-stimulated glucagon levels were also increased. The I/G molar ratio in portal vein blood of progesterone treated rats remained unaltered and the hepatic lipogenic and gluconeogenic enzyme activities were similar to control animals. These data suggest that insulin activity is increased relative to glucagon in the liver of oestradiol-treated rats due to the rise in portal vein I/G ratio. The changes in liver lipogenic and gluconeogenic enzymes and the alterations in fasting plasma triglycerides and glucose in response to oestrogens could be secondary to this effect."}
{"id": "PMID:19261", "title": "Effects of bile and bile acids on cultured human fibroblasts.", "content": "Impaired healing induced by leakage of bile has been postulated as one factor responsible for complications after reconstructive bile duct surgery. The cytotoxicity of human bile and its major bile acids on cultured human fibroblasts was therefore studied by evaluation of their effects on cell morphology and growth, on synthesis and secretion of 35SO4-mucopolysaccharides and on release of a lysosomal enzyme. Normal human fibroblasts derived from a standard culture strain (MRC-5) were grown to confluence and exposed to: (1) sterile human T-tube bile, (2) a mixture of bile acids resembling that of human bile, or (3) various concentrations of the glycine- and taurine conjugates of cholic, chenodeoxycholic or deoxycholic acid. Medium containing whole bile (total bile acid concentration 0.25, 0.75 or 1.6 mmol/l) exerted time and dose dependent cytotoxic effects on morphology and growth and release of lysosomal enzyme. Synthesis and secretion of 35SO4-mucopolysaccharides were markedly inhibited. The bile acid mixture exhibited the same time and dose dependent effects. The conjugates of deoxycholic acid were found to be the most toxic of the individual bile acids studied.", "contents": "Effects of bile and bile acids on cultured human fibroblasts. Impaired healing induced by leakage of bile has been postulated as one factor responsible for complications after reconstructive bile duct surgery. The cytotoxicity of human bile and its major bile acids on cultured human fibroblasts was therefore studied by evaluation of their effects on cell morphology and growth, on synthesis and secretion of 35SO4-mucopolysaccharides and on release of a lysosomal enzyme. Normal human fibroblasts derived from a standard culture strain (MRC-5) were grown to confluence and exposed to: (1) sterile human T-tube bile, (2) a mixture of bile acids resembling that of human bile, or (3) various concentrations of the glycine- and taurine conjugates of cholic, chenodeoxycholic or deoxycholic acid. Medium containing whole bile (total bile acid concentration 0.25, 0.75 or 1.6 mmol/l) exerted time and dose dependent cytotoxic effects on morphology and growth and release of lysosomal enzyme. Synthesis and secretion of 35SO4-mucopolysaccharides were markedly inhibited. The bile acid mixture exhibited the same time and dose dependent effects. The conjugates of deoxycholic acid were found to be the most toxic of the individual bile acids studied."}
{"id": "PMID:19263", "title": "Mechanisms of B cell tolerance: I. Dynamic nature of the induction of hapten-specific unresponsiveness by hapten-conjugated pneumococcal polysaccharide.", "content": "Exposure of 2,4-dinitrophenyl (DNP)-hemocyanin-primed spleen cells to DNP-conjugated pneumococcal polysaccharide (DNP-S3) in vivo or in vitro renders such cells unresponsive to DNP-hemocyanin challenge following adoptive transfer. The unresponsiveness is hapten-specific, independent of the presence of T cells and adherent cells, and not due to either toxic effect of S3 or carry-over of tolerogenic amounts of cell-bound DNP-S3, and thus presumably represents a model of B cell tolerance. The degree of suppression induced depends upon the dose of the tolerogen and most strikingly on the duration of exposure of cells to the tolerogen. Thus 2 to 6 h exposure to DNP-S3 has an insignificant effect on anti-DNP responses, while 24 and 48 h exposures in vitro and in vivo are highly suppressive. Such a dynamic process of tolerance induction suggests a \"multiple hit\" phenomenon, implying the generation of suppressive signals by repeated cycles of tolerogen-receptor interactions. The process can be interrupted by removal of extracellular DNP-S3, although this does not reverse the unresponsiveness that has already been induced.", "contents": "Mechanisms of B cell tolerance: I. Dynamic nature of the induction of hapten-specific unresponsiveness by hapten-conjugated pneumococcal polysaccharide. Exposure of 2,4-dinitrophenyl (DNP)-hemocyanin-primed spleen cells to DNP-conjugated pneumococcal polysaccharide (DNP-S3) in vivo or in vitro renders such cells unresponsive to DNP-hemocyanin challenge following adoptive transfer. The unresponsiveness is hapten-specific, independent of the presence of T cells and adherent cells, and not due to either toxic effect of S3 or carry-over of tolerogenic amounts of cell-bound DNP-S3, and thus presumably represents a model of B cell tolerance. The degree of suppression induced depends upon the dose of the tolerogen and most strikingly on the duration of exposure of cells to the tolerogen. Thus 2 to 6 h exposure to DNP-S3 has an insignificant effect on anti-DNP responses, while 24 and 48 h exposures in vitro and in vivo are highly suppressive. Such a dynamic process of tolerance induction suggests a \"multiple hit\" phenomenon, implying the generation of suppressive signals by repeated cycles of tolerogen-receptor interactions. The process can be interrupted by removal of extracellular DNP-S3, although this does not reverse the unresponsiveness that has already been induced."}
{"id": "PMID:19265", "title": "pD2-, pA2- and pD2'-values of a series of compounds in a histaminic and a cholinergic system.", "content": "(1) Affinity and intrinsic activity values of 75 compounds for a histaminergic and a cholinergic system are presented. The quantitative correlations between the affinity values of 35 compounds and some physicochemical constants (Van der Waals volume, lipophilicity, number of hydrogen atoms on the protonated amine) are discussed. (2) Absence of systematic differences between pD2 and pA2 of partial agonists supports the assumption that these values are equivalent expressions of the same affinity. (3) The \"mimetic moiety\" in a number of the antihistaminic test compounds hardly contributes to their affinity. The affinity mainly depends on an interaction tendency with additional receptor areas. (4) The correlation between pA2 and pD2' of the whole series of compounds in the histaminergic system is artificial. The method only allows determination of both values if their ratio lies between certain limits. (5) The correlation between pA2 and pD2' for 16 closely related compounds in the guinea pig ileum and for nearly all compounds in the rat intestine has to be explained by an influence of the structural differences on drug transference and/or the less specific binding forces. (6) The metactoid receptors in the two systems are different structures. (7) Possible molecular modifications to maximize the separation of antihistaminic form cholinergic affinity are suggested.", "contents": "pD2-, pA2- and pD2'-values of a series of compounds in a histaminic and a cholinergic system. (1) Affinity and intrinsic activity values of 75 compounds for a histaminergic and a cholinergic system are presented. The quantitative correlations between the affinity values of 35 compounds and some physicochemical constants (Van der Waals volume, lipophilicity, number of hydrogen atoms on the protonated amine) are discussed. (2) Absence of systematic differences between pD2 and pA2 of partial agonists supports the assumption that these values are equivalent expressions of the same affinity. (3) The \"mimetic moiety\" in a number of the antihistaminic test compounds hardly contributes to their affinity. The affinity mainly depends on an interaction tendency with additional receptor areas. (4) The correlation between pA2 and pD2' of the whole series of compounds in the histaminergic system is artificial. The method only allows determination of both values if their ratio lies between certain limits. (5) The correlation between pA2 and pD2' for 16 closely related compounds in the guinea pig ileum and for nearly all compounds in the rat intestine has to be explained by an influence of the structural differences on drug transference and/or the less specific binding forces. (6) The metactoid receptors in the two systems are different structures. (7) Possible molecular modifications to maximize the separation of antihistaminic form cholinergic affinity are suggested."}
{"id": "PMID:19266", "title": "Regional effects of neuroleptics on dopamine metabolism and dopamine-sensitive adenylate cyclase activity.", "content": "The effect of haloperidol, chlorpromazine, thioridazine and sulpride on the levels of DOPAC and HVA, as an index of DA turnover, and on the activity of DA-stimulated adenylate cyclase was investigated inthe striatum, the nucleus accumbens and the tuberculum olfactorium of the rat brain. Haloperidol, chlorpromazine and thioridazine caused a more marked increase in DA turnover in the striatum than in the mesolimbic areas, while the reverse was true for sulpiride. In contrast, although the relative potency of these compounds varied greatly, the Ki of each drug for the DA-sensitive adenylate cyclase was similar in three structures of rat brain. The results indicate that in the three brain structures investigated there was no correlation between the differential effects of neuroleptics on dopamine turnover in vivo and the blockade by these drug of the DA-sensitive adenylate cyclase activity in vitro.", "contents": "Regional effects of neuroleptics on dopamine metabolism and dopamine-sensitive adenylate cyclase activity. The effect of haloperidol, chlorpromazine, thioridazine and sulpride on the levels of DOPAC and HVA, as an index of DA turnover, and on the activity of DA-stimulated adenylate cyclase was investigated inthe striatum, the nucleus accumbens and the tuberculum olfactorium of the rat brain. Haloperidol, chlorpromazine and thioridazine caused a more marked increase in DA turnover in the striatum than in the mesolimbic areas, while the reverse was true for sulpiride. In contrast, although the relative potency of these compounds varied greatly, the Ki of each drug for the DA-sensitive adenylate cyclase was similar in three structures of rat brain. The results indicate that in the three brain structures investigated there was no correlation between the differential effects of neuroleptics on dopamine turnover in vivo and the blockade by these drug of the DA-sensitive adenylate cyclase activity in vitro."}
{"id": "PMID:19267", "title": "The effect of antipsychotic drugs and their clinically inactive analogs on dopamine metabolism.", "content": "Changes in dopamine metabolite levels in the rat striatum and tuberculum olfactorium, following the administration of three non-antipsychotic butyrophenones (AL-499, AHR-1900 and U-25,927) and a non-antipsychotic benzazepine (SCH-12,679), were compared to the effects seen following the antipsychotics haloperidol, chlorpromazine and clozapine. The non-antipsychotics, although clinically ineffective, were reported as active in a variety of animal screening tests. Haloperidol, chlorpromazine and clozapine produced a dose-dependent increase in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in both regions. Of the non-antipsychotic drugs only AHR-1900 significantly elevated the level of DOPAC, however, the slope of its dose-response curve was atypically flat in comparison to the dose-response curves of drugs with known antipsychotic efficacy. Moreover, the maximal effect of AHR-1900 observed at a dose of 40 mg/kg was less than the ED50 effect of haloperidol which occurs at a 250 fold lower dose. It is concluded that the dose-dependent elevation of DOPAC in the striatum and tuberculum olfactorium of the rat is a good predictor of antipsychotic efficacy.", "contents": "The effect of antipsychotic drugs and their clinically inactive analogs on dopamine metabolism. Changes in dopamine metabolite levels in the rat striatum and tuberculum olfactorium, following the administration of three non-antipsychotic butyrophenones (AL-499, AHR-1900 and U-25,927) and a non-antipsychotic benzazepine (SCH-12,679), were compared to the effects seen following the antipsychotics haloperidol, chlorpromazine and clozapine. The non-antipsychotics, although clinically ineffective, were reported as active in a variety of animal screening tests. Haloperidol, chlorpromazine and clozapine produced a dose-dependent increase in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in both regions. Of the non-antipsychotic drugs only AHR-1900 significantly elevated the level of DOPAC, however, the slope of its dose-response curve was atypically flat in comparison to the dose-response curves of drugs with known antipsychotic efficacy. Moreover, the maximal effect of AHR-1900 observed at a dose of 40 mg/kg was less than the ED50 effect of haloperidol which occurs at a 250 fold lower dose. It is concluded that the dose-dependent elevation of DOPAC in the striatum and tuberculum olfactorium of the rat is a good predictor of antipsychotic efficacy."}
{"id": "PMID:19268", "title": "The anticonvulsant action of methazolamide in mice: antagonism by various inhibitors of dopamine beta-hydroxylase.", "content": "The dopamine beta-hydroxylase inhibitors, FLA-63 and picolinic acid, antagonized the anticonvulsant action of methazolamine in mice; disulfiram and pyrimidinethiol were inactive. FLA-63 and picolinic acid, but not disulfiram or pyrimidinethiol prevented pheniprazine restoration of the anticonvulsant action of methazolamide in reserpinized mice. The present findings clearly demonstrate that differences exist among inhibitors of dopamine beta-hydroxylase regarding their ability to antagonize the anticonvulsant action of methazolamide under various test conditions.", "contents": "The anticonvulsant action of methazolamide in mice: antagonism by various inhibitors of dopamine beta-hydroxylase. The dopamine beta-hydroxylase inhibitors, FLA-63 and picolinic acid, antagonized the anticonvulsant action of methazolamine in mice; disulfiram and pyrimidinethiol were inactive. FLA-63 and picolinic acid, but not disulfiram or pyrimidinethiol prevented pheniprazine restoration of the anticonvulsant action of methazolamide in reserpinized mice. The present findings clearly demonstrate that differences exist among inhibitors of dopamine beta-hydroxylase regarding their ability to antagonize the anticonvulsant action of methazolamide under various test conditions."}
{"id": "PMID:19269", "title": "Acetylcholine-norepinephrine interactions on potassium movements in the sinus node.", "content": "Possible adrenergic mechanisms involved in acetylcholine (ACh) induced potassium movements in the sinus node have been investigated using a tracer potassium (42K) and a microelectrode technique. The ACh-induced increase in 42K uptake was enhanced by propranolol and was unaffected by phentolamine. Reserpinization neither prevented the ACh-induced increase in 42K uptake nor the enhanced effect in the presence of propranolol. In reserpinized preparations, ACh-induced 42K uptake was the same before and after norepinephrine (NE) administration, but was greater after acute reserpinization. NE alone induced an increase in 42K uptake but the simultaneous administration of ACh and NE provoked an increase in 42K uptake similar to that obtained with ACh alone. When both neuromediators and atropine were given simultaneously, an increase in 42K uptake did not occur. Thus, the ACh induces an increase in 42K uptake independently of NE. ACh antagonizes the NE effect on 42K uptake independently of a muscarinic interaction.", "contents": "Acetylcholine-norepinephrine interactions on potassium movements in the sinus node. Possible adrenergic mechanisms involved in acetylcholine (ACh) induced potassium movements in the sinus node have been investigated using a tracer potassium (42K) and a microelectrode technique. The ACh-induced increase in 42K uptake was enhanced by propranolol and was unaffected by phentolamine. Reserpinization neither prevented the ACh-induced increase in 42K uptake nor the enhanced effect in the presence of propranolol. In reserpinized preparations, ACh-induced 42K uptake was the same before and after norepinephrine (NE) administration, but was greater after acute reserpinization. NE alone induced an increase in 42K uptake but the simultaneous administration of ACh and NE provoked an increase in 42K uptake similar to that obtained with ACh alone. When both neuromediators and atropine were given simultaneously, an increase in 42K uptake did not occur. Thus, the ACh induces an increase in 42K uptake independently of NE. ACh antagonizes the NE effect on 42K uptake independently of a muscarinic interaction."}
{"id": "PMID:19277", "title": "Modification of the action of pentagastrin on acid secretion by botulinum toxin.", "content": "I.v botulinum toxin after 60-90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.", "contents": "Modification of the action of pentagastrin on acid secretion by botulinum toxin. I.v botulinum toxin after 60-90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin."}
{"id": "PMID:19279", "title": "The effect of ion pair formation on the antimuscarinic activity of methantheline.", "content": "The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.", "contents": "The effect of ion pair formation on the antimuscarinic activity of methantheline. The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment."}
{"id": "PMID:19281", "title": "Interaction of extrinsic fluorescent probes with E. coli glutamine synthetase.", "content": "Binding of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) to adenylylated (E--11) glutamine synthetase is cooperative and time-dependent, with 3 dye sites per subunit. In fluorescence polarization experiments TNS and pyrene butyrate give normalized Perrin plots that indicate a symmetrical arrangement of dye excited state dipoles, relative to the rotational axis of the oblate ellipsoid of the dodecameric native enzyme.", "contents": "Interaction of extrinsic fluorescent probes with E. coli glutamine synthetase. Binding of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) to adenylylated (E--11) glutamine synthetase is cooperative and time-dependent, with 3 dye sites per subunit. In fluorescence polarization experiments TNS and pyrene butyrate give normalized Perrin plots that indicate a symmetrical arrangement of dye excited state dipoles, relative to the rotational axis of the oblate ellipsoid of the dodecameric native enzyme."}
{"id": "PMID:19282", "title": "Effects of alpha- and beta-adrenergic blockers on the actions of noradrenaline on body temperature in the newborn guinea-pig.", "content": "The effect of NA injected into the lateral cerebral ventricle on Tc was blocked by alpha-adrenergic receptor blockers, but not by beta-receptor blockers, whereas the effect of systemically administered NA was blocked by i.p. administered beta-receptor blockers, but not by alpha-blockers.", "contents": "Effects of alpha- and beta-adrenergic blockers on the actions of noradrenaline on body temperature in the newborn guinea-pig. The effect of NA injected into the lateral cerebral ventricle on Tc was blocked by alpha-adrenergic receptor blockers, but not by beta-receptor blockers, whereas the effect of systemically administered NA was blocked by i.p. administered beta-receptor blockers, but not by alpha-blockers."}
{"id": "PMID:19283", "title": "Chemical studies of marine invertebrates. XXVII. On the absolute configuration of aromadendrane sesquiterpenes from the soft coral Cespitularia aff. subviridis.", "content": "Allo-aromadendrene, (-)viridiflorol and (+)ledol have been identified as minor constituents of the soft coral Cespitularia aff. subviridis.", "contents": "Chemical studies of marine invertebrates. XXVII. On the absolute configuration of aromadendrane sesquiterpenes from the soft coral Cespitularia aff. subviridis. Allo-aromadendrene, (-)viridiflorol and (+)ledol have been identified as minor constituents of the soft coral Cespitularia aff. subviridis."}
{"id": "PMID:19285", "title": "Inhibitory effect of fentonium on gastric acid secretion in different laboratory animals.", "content": "The influence of fentonium, a new derivative of hyoscyamine, on the gastric secretion has been evaluated in rats, cats and dogs. The compound appeared to be able to markedly reduce the gastric hypersecretion produced by pentagastrin, caerulein and bethanechol; its antagonizing activity against histamine stimulation was poor.", "contents": "Inhibitory effect of fentonium on gastric acid secretion in different laboratory animals. The influence of fentonium, a new derivative of hyoscyamine, on the gastric secretion has been evaluated in rats, cats and dogs. The compound appeared to be able to markedly reduce the gastric hypersecretion produced by pentagastrin, caerulein and bethanechol; its antagonizing activity against histamine stimulation was poor."}
{"id": "PMID:19307", "title": "Hydrogen ion and carbon dioxide content of the oviductal fluid of the rhesus monkey (Macaca mulatta).", "content": "The pH in the oviduct lumen of adult female rhesus monkey (Macaca mulatta) during the menstrual cycle was measured by means of miniaturized pH electrodes. Two types were used: one was a flexible electrode 1.4 mm in diameter; the other was a rigid electrode 0.8 mm in diameter. The same results were obtained with both types. For PCO2 measurements, the pH electrodes was converted to a Severinghaus tyep electrode covered with a Teflon membrane. During the follicular phase, the pH remains constant in the range 7.1 to 7.3. In association with ovulation, there is a sudden increase in the pH to the range 7.5 to 7.8. The pH remains high through the luteal phase. The PCO2 values obtained showed no evident changes with day of cycle. The range of values estimated was wide because of drift in electrode calibration, with the average level about 89 Torr, compared with 40 Torr for blood. At the average pH of 7.2 in the follicular phase, this value of PCO2 corresponds to 35 mM HCO3-; at the average pH of 7.6 of the secretory phase, this value corresponds to 90 mM HCO3-. This increase in pH and HCO3- after ovulation would be expected to enhance dispersal of corona cells during fertilization and to provide a favorable environment for the developing embryo.", "contents": "Hydrogen ion and carbon dioxide content of the oviductal fluid of the rhesus monkey (Macaca mulatta). The pH in the oviduct lumen of adult female rhesus monkey (Macaca mulatta) during the menstrual cycle was measured by means of miniaturized pH electrodes. Two types were used: one was a flexible electrode 1.4 mm in diameter; the other was a rigid electrode 0.8 mm in diameter. The same results were obtained with both types. For PCO2 measurements, the pH electrodes was converted to a Severinghaus tyep electrode covered with a Teflon membrane. During the follicular phase, the pH remains constant in the range 7.1 to 7.3. In association with ovulation, there is a sudden increase in the pH to the range 7.5 to 7.8. The pH remains high through the luteal phase. The PCO2 values obtained showed no evident changes with day of cycle. The range of values estimated was wide because of drift in electrode calibration, with the average level about 89 Torr, compared with 40 Torr for blood. At the average pH of 7.2 in the follicular phase, this value of PCO2 corresponds to 35 mM HCO3-; at the average pH of 7.6 of the secretory phase, this value corresponds to 90 mM HCO3-. This increase in pH and HCO3- after ovulation would be expected to enhance dispersal of corona cells during fertilization and to provide a favorable environment for the developing embryo."}
{"id": "PMID:19327", "title": "Determining optimum dose and acute tolerance of triazolam.", "content": "The present two-phase study was designed to determine the optimum hynotic dose of triazolam and to assess any evidence of acute tolerance. Subjective and objective data were used to assess hypnotic efficacy. In the dose-titration phase, the dose of triazolam was increased in 0-5 mg increments to the highest level tolerated by each individual patient. Maximum tolerable doses ranged between 0-5 and 3-0 mg; however, all subjects experienced maximum therapeutic effect at 1-5 mg triazolam. During the 4-night acute tolerance portion of the study no clear evidence of tolerance was found.", "contents": "Determining optimum dose and acute tolerance of triazolam. The present two-phase study was designed to determine the optimum hynotic dose of triazolam and to assess any evidence of acute tolerance. Subjective and objective data were used to assess hypnotic efficacy. In the dose-titration phase, the dose of triazolam was increased in 0-5 mg increments to the highest level tolerated by each individual patient. Maximum tolerable doses ranged between 0-5 and 3-0 mg; however, all subjects experienced maximum therapeutic effect at 1-5 mg triazolam. During the 4-night acute tolerance portion of the study no clear evidence of tolerance was found."}
{"id": "PMID:19328", "title": "Antihypertensive effect and tolerability of metoprolol during long-term treatment: a multicentre study.", "content": "One hundred and forty-seven patients with essential hypertension participated in this multicentre study. The results indicate that metoprolol in a dosage of 150-450 mg daily is an effective and well tolerated therapy both in patients previously untreated and in patients unsatisfactorily treated with other antihypertensive agents.", "contents": "Antihypertensive effect and tolerability of metoprolol during long-term treatment: a multicentre study. One hundred and forty-seven patients with essential hypertension participated in this multicentre study. The results indicate that metoprolol in a dosage of 150-450 mg daily is an effective and well tolerated therapy both in patients previously untreated and in patients unsatisfactorily treated with other antihypertensive agents."}
{"id": "PMID:19330", "title": "6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin.", "content": "Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin containing 3 mg./ml. glucose and 0, 200, 400, or 800 microU./ml. of rat insulin, and the glucose-6-phosphate (G6P) and 6-phosphogluconate (6PG) contents were determined by enzymatic cycling. In response to a rise in the concentration of insulin, the 6PG/G6P ratio decreased. A close relationship was observed between this decrease of 6PG/G6P ratio and the net insulin release, the absolute rate of glucose oxidation via the pentose phosphate cycle, and the NADPH/NADP ratios measured under similar conditions. The results suggest that exogenous insulin, directly or indirectly, regulates the pentose cycle activity in the pancreatic islets at the G6P dehydrogenase step.", "contents": "6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin. Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin containing 3 mg./ml. glucose and 0, 200, 400, or 800 microU./ml. of rat insulin, and the glucose-6-phosphate (G6P) and 6-phosphogluconate (6PG) contents were determined by enzymatic cycling. In response to a rise in the concentration of insulin, the 6PG/G6P ratio decreased. A close relationship was observed between this decrease of 6PG/G6P ratio and the net insulin release, the absolute rate of glucose oxidation via the pentose phosphate cycle, and the NADPH/NADP ratios measured under similar conditions. The results suggest that exogenous insulin, directly or indirectly, regulates the pentose cycle activity in the pancreatic islets at the G6P dehydrogenase step."}
{"id": "PMID:19331", "title": "Effect of caerulein on gamma-glutamyl transpeptidase and alkaline phosphatase in the duodenal juice in chronic pancreatitis.", "content": "During infusion of caerulein, the output of gamma-glutamyl transpeptidase and biliary alkaline phosphatase is significantly more increased in chronic pancreatitis patients than in normal subjects. The presence of the gall-bladder is necessary to observe this effect of caerulein. It is not related to the discharge of large amounts of both enzymes by the diseases pancreas.", "contents": "Effect of caerulein on gamma-glutamyl transpeptidase and alkaline phosphatase in the duodenal juice in chronic pancreatitis. During infusion of caerulein, the output of gamma-glutamyl transpeptidase and biliary alkaline phosphatase is significantly more increased in chronic pancreatitis patients than in normal subjects. The presence of the gall-bladder is necessary to observe this effect of caerulein. It is not related to the discharge of large amounts of both enzymes by the diseases pancreas."}
{"id": "PMID:19333", "title": "Inhibitory effect of sulpiride on cinchophen gastric ulceration in dogs.", "content": "An intraventricular administration of sulpiride suppressed the experimental cinchophen ulcer, thereby the effect of repeated administration of the material on cinchophen ulcerogenesis is evident, whereas intermittent administration lacked this effect. Such an effect as reducing experimental cinchophen ulceration, which is due to central neurohumoral mechanism, following intraventricular infusion of sulpiride appears to be ascribable to a chemical blockage of the hypothalamic structure. It can thus be concluded that sulpiride acts principally at the level of hypothalamus. Its inhibitory action on cinchophen gastric ulcer development is probably exerted via the hypothalomo-pituitary-adrenal axis, which is essential to the occurrence of an ulcer, and may be regarded as favoring the central neurohumoral theory of cinchophen ulcerogenesis.", "contents": "Inhibitory effect of sulpiride on cinchophen gastric ulceration in dogs. An intraventricular administration of sulpiride suppressed the experimental cinchophen ulcer, thereby the effect of repeated administration of the material on cinchophen ulcerogenesis is evident, whereas intermittent administration lacked this effect. Such an effect as reducing experimental cinchophen ulceration, which is due to central neurohumoral mechanism, following intraventricular infusion of sulpiride appears to be ascribable to a chemical blockage of the hypothalamic structure. It can thus be concluded that sulpiride acts principally at the level of hypothalamus. Its inhibitory action on cinchophen gastric ulcer development is probably exerted via the hypothalomo-pituitary-adrenal axis, which is essential to the occurrence of an ulcer, and may be regarded as favoring the central neurohumoral theory of cinchophen ulcerogenesis."}
{"id": "PMID:19334", "title": "Role of intragastric pressure, pH, and pepsin in gastric ulceration in the rat.", "content": "A method of continuous gastric perfusion with \"artificial gastric juice\" was used in a study of individual factors (intragastric pressure, pH, and pepsin) known to participate in the pathogenesis of peptic ulcers. This method allowed change of only one factor at a time, while the other two remained constant. The gastric mucosa of normal rats, fasted for 48 hr, was found to be resistant to the ulcerogenic effects of artificial gastric juice perfused through the stomach for 6 hr without increasing the intragastric pressure. Perfusion of hydrochloric acid (pH 1.3) under increasing pressure produced ulceration of the corpus as well as forestomach portion of the stomach. The degree of gastric ulceration paralleled increases in intragastric pressure, acidity, and pepsin proteolytic activity. Inhibition of pepsin activity by a pepsin inhibitor protected the gastric mucosa even at the very low pH of 1.3. These results demonstrate that under the experimental conditions used, hydrochloric acid alone in the absence of pepsin does not produce ulceration of the rat stomach.", "contents": "Role of intragastric pressure, pH, and pepsin in gastric ulceration in the rat. A method of continuous gastric perfusion with \"artificial gastric juice\" was used in a study of individual factors (intragastric pressure, pH, and pepsin) known to participate in the pathogenesis of peptic ulcers. This method allowed change of only one factor at a time, while the other two remained constant. The gastric mucosa of normal rats, fasted for 48 hr, was found to be resistant to the ulcerogenic effects of artificial gastric juice perfused through the stomach for 6 hr without increasing the intragastric pressure. Perfusion of hydrochloric acid (pH 1.3) under increasing pressure produced ulceration of the corpus as well as forestomach portion of the stomach. The degree of gastric ulceration paralleled increases in intragastric pressure, acidity, and pepsin proteolytic activity. Inhibition of pepsin activity by a pepsin inhibitor protected the gastric mucosa even at the very low pH of 1.3. These results demonstrate that under the experimental conditions used, hydrochloric acid alone in the absence of pepsin does not produce ulceration of the rat stomach."}
{"id": "PMID:19335", "title": "Binding properties in vitro of antacids for conjugated bile acids.", "content": "The binding properties of various commercial antacids for pure conjugated bile acids in an aqueous solution or the bile acids present in human gallbladder bile were characterized. Aluminum hydroxide was a potent binding agent, similar in affinity and capacity to cholestyramine. With aluminum hydroxide, dihydroxy bile acid conjugates were bound more strongly than trihydroxy bile acid conjugates, and glycine conjugates were bound more strongly than taurine conjugates; pH had no effect per se on binding. Magnesium hydroxide and aluminum phosphate bound bile acids much more weakly. Aluminum hydroxide warrants exploration in therapeutic situations in which bile acid binding is sought.", "contents": "Binding properties in vitro of antacids for conjugated bile acids. The binding properties of various commercial antacids for pure conjugated bile acids in an aqueous solution or the bile acids present in human gallbladder bile were characterized. Aluminum hydroxide was a potent binding agent, similar in affinity and capacity to cholestyramine. With aluminum hydroxide, dihydroxy bile acid conjugates were bound more strongly than trihydroxy bile acid conjugates, and glycine conjugates were bound more strongly than taurine conjugates; pH had no effect per se on binding. Magnesium hydroxide and aluminum phosphate bound bile acids much more weakly. Aluminum hydroxide warrants exploration in therapeutic situations in which bile acid binding is sought."}
{"id": "PMID:19336", "title": "Obstructive jaundice after bone marrow transplantation.", "content": "Jaundice after bone marrow transplantation is usually a consequence of graft versus host disease. Reported is a patient who presented with obstructive jaundice several months after a successful marrow allograft. Despite a benign bone marrow examination, abdominal ultrasound, upper gastrointestinal series, and endoscopic biopsy were utilized to diagnose recurrent leukemia at the pancreatic head and descending duodenum. The entities of graft versus host disease as related to jaundice, and gastrointestinal leukemia, in the presence of a \"remission\" bone marrow, are reviewed.", "contents": "Obstructive jaundice after bone marrow transplantation. Jaundice after bone marrow transplantation is usually a consequence of graft versus host disease. Reported is a patient who presented with obstructive jaundice several months after a successful marrow allograft. Despite a benign bone marrow examination, abdominal ultrasound, upper gastrointestinal series, and endoscopic biopsy were utilized to diagnose recurrent leukemia at the pancreatic head and descending duodenum. The entities of graft versus host disease as related to jaundice, and gastrointestinal leukemia, in the presence of a \"remission\" bone marrow, are reviewed."}
{"id": "PMID:19337", "title": "Peptic ulcer disease--a heterogeneous group of disorders?", "content": "The familial aggregation of peptic ulcer disease has been well established, as has its association with such clear-cut genetic factors as blood group O and nonsecretor status. However, the genetics of this disorder, or group of disorders, is still in question. Polygenic inheritance is the prevailing hypothesis that has been proposed for peptic ulcer. This hypothesis was based primarily on the exclusion of a simple mode of inheritance for all ulcer disease. Genetic heterogeneity is an alternative hypothesis that can explain both the familial aggregation of peptic ulcer disease and the lack of a simple Mendelian pattern of inheritance. The evidence for genetic heterogeneity in peptic ulcer disease is reviewed, and studies are proposed to test this hypothesis.", "contents": "Peptic ulcer disease--a heterogeneous group of disorders? The familial aggregation of peptic ulcer disease has been well established, as has its association with such clear-cut genetic factors as blood group O and nonsecretor status. However, the genetics of this disorder, or group of disorders, is still in question. Polygenic inheritance is the prevailing hypothesis that has been proposed for peptic ulcer. This hypothesis was based primarily on the exclusion of a simple mode of inheritance for all ulcer disease. Genetic heterogeneity is an alternative hypothesis that can explain both the familial aggregation of peptic ulcer disease and the lack of a simple Mendelian pattern of inheritance. The evidence for genetic heterogeneity in peptic ulcer disease is reviewed, and studies are proposed to test this hypothesis."}
{"id": "PMID:19338", "title": "Effect of beta adrenergic blocking drugs on the renin-aldosterone system, sodium excretion, and renal hemodynamics in cirrhosis with ascites.", "content": "As a result of effective beta adrenergic blockade with either propranolol or practolol, plasma renin activity was suppressed in all of 11 patients with cirrhosis and ascites. In contrast, the effect on the rate of renal excretion of aldosterone was variable, suggesting that factors other than the renin-angiotension system are responsible for the control of aldosterone secretion in cirrhosis. The changes in aldosterone could not be explained on the basis of changes in the plasma concentrations of potassium or sodium. The renal sodium excretion was inversely related to the values for aldosterone both before and after beta adrenergic blockade, indicating a major role for aldosterone in regulating sodium excretion. A number of patients had an abnormal intrarenal distribution of plasma flow with a relative hypoperfusion of the renin-secreting outer cortical nephrons. Plasma renin activity was inversely related to outer cortical plasma flow, suggesting that the reduced outer cortical flow may be a stimulus to increased renin secretion. Because the abnormal intrarenal hemodynamic pattern was not corrected by suppression of plasma renin activity, and presumably angiotension II concentrations, it is unlikely that it is attributable to the known renal vasonconstrictor effects of angiotensin II.", "contents": "Effect of beta adrenergic blocking drugs on the renin-aldosterone system, sodium excretion, and renal hemodynamics in cirrhosis with ascites. As a result of effective beta adrenergic blockade with either propranolol or practolol, plasma renin activity was suppressed in all of 11 patients with cirrhosis and ascites. In contrast, the effect on the rate of renal excretion of aldosterone was variable, suggesting that factors other than the renin-angiotension system are responsible for the control of aldosterone secretion in cirrhosis. The changes in aldosterone could not be explained on the basis of changes in the plasma concentrations of potassium or sodium. The renal sodium excretion was inversely related to the values for aldosterone both before and after beta adrenergic blockade, indicating a major role for aldosterone in regulating sodium excretion. A number of patients had an abnormal intrarenal distribution of plasma flow with a relative hypoperfusion of the renin-secreting outer cortical nephrons. Plasma renin activity was inversely related to outer cortical plasma flow, suggesting that the reduced outer cortical flow may be a stimulus to increased renin secretion. Because the abnormal intrarenal hemodynamic pattern was not corrected by suppression of plasma renin activity, and presumably angiotension II concentrations, it is unlikely that it is attributable to the known renal vasonconstrictor effects of angiotensin II."}
{"id": "PMID:19340", "title": "Crohn's disease involving the colon: an audit of clinical management.", "content": "This paper describes the clinical management of 204 patients with Crohn's disease involving the colon who have been reviewed regularly for many years. The results have been analyzed to define the morbidity, mortality, and long term prognosis of the disorder. Despite a high morbidity, the long term prognosis is good. Although the mean interval since the onset of symptoms is more than 13 years, 77% of the patients are symptom-free and 60% have normal laboratory indices. This analysis suggests that until the etiology of Crohn's disease is established and a specific therapy is developed, good results can be obtained with regular medical review and appropriate surgical treatment with the limited use of immunosuppressive agents or total parenteral nutrition.", "contents": "Crohn's disease involving the colon: an audit of clinical management. This paper describes the clinical management of 204 patients with Crohn's disease involving the colon who have been reviewed regularly for many years. The results have been analyzed to define the morbidity, mortality, and long term prognosis of the disorder. Despite a high morbidity, the long term prognosis is good. Although the mean interval since the onset of symptoms is more than 13 years, 77% of the patients are symptom-free and 60% have normal laboratory indices. This analysis suggests that until the etiology of Crohn's disease is established and a specific therapy is developed, good results can be obtained with regular medical review and appropriate surgical treatment with the limited use of immunosuppressive agents or total parenteral nutrition."}
{"id": "PMID:19341", "title": "Effect of acetylsalicylic acid on the amphibian gastric mucosa. I. Electrophysiological and permeability changes.", "content": "The effects of acetylsalicylic acid on the in vitro bullfrog gastric mucosa were defined. After mucosal exposure of 10 or 20 mM acetylsalicylic acid, a characteristic series of changes evolved. The potential difference and resistance rose initially. After 15 to 30 min the potential difference declined to zero. Transmucosal resistance remained elevated considerably longer but began to decline toward zero after 30 to 60 min of exposure. Mucosal permeability to mannitol increased as transmucosal resistance declined, but was not markedly elevated until the 2nd hr of exposure to acetylsalicylic acid. The initial rise of potential difference was associated with inhibition of H+ secretion whereas the later decline of potential difference was due to inhibition of Cl- transport. The abolition of short circuit current could not be attributed to mucosal to serosal flux of acetylsalicylate.", "contents": "Effect of acetylsalicylic acid on the amphibian gastric mucosa. I. Electrophysiological and permeability changes. The effects of acetylsalicylic acid on the in vitro bullfrog gastric mucosa were defined. After mucosal exposure of 10 or 20 mM acetylsalicylic acid, a characteristic series of changes evolved. The potential difference and resistance rose initially. After 15 to 30 min the potential difference declined to zero. Transmucosal resistance remained elevated considerably longer but began to decline toward zero after 30 to 60 min of exposure. Mucosal permeability to mannitol increased as transmucosal resistance declined, but was not markedly elevated until the 2nd hr of exposure to acetylsalicylic acid. The initial rise of potential difference was associated with inhibition of H+ secretion whereas the later decline of potential difference was due to inhibition of Cl- transport. The abolition of short circuit current could not be attributed to mucosal to serosal flux of acetylsalicylate."}
{"id": "PMID:19344", "title": "Characterization of Salmonella typhimurium mutants with altered glutamine synthetase activity.", "content": "A number of glutamine auxotrophs of Salmonella typhimurium were isolated and characterized genetically. Three of the mutations appear to be closely linked and are complemented by episomes carrying the glnA region of Escherichia coli. The lesions in these strains are approximately 20% linked by P1 transduction with a mutation in the rha gene, but are unlinked to ilv. Another mutation causing glutamine auxotrophy in strain JB674 is genetically distinct from the others. Strain JB674 grown in glucose medium containing ammonia as the nitrogen source has reduced levels of glutamine synthetase that is more adenylylated than in the parent strain, suggesting that the enzyme can not be deadenylylated normally. The lesion causing glutamine auxotrophy in JB674 lies in the region corresponding to the glnB and glnE genes affecting glutamine synthetase modification in Klebsiella areogenes. Four Gln+ revertants of JB674 have glutamine synthetase activities 4 to 6 fold higher than normal. One mutation causing this increased enzyme synthesis has been shown by three-factor crosses with the glnA mutations to lie near or within the glnA gene.", "contents": "Characterization of Salmonella typhimurium mutants with altered glutamine synthetase activity. A number of glutamine auxotrophs of Salmonella typhimurium were isolated and characterized genetically. Three of the mutations appear to be closely linked and are complemented by episomes carrying the glnA region of Escherichia coli. The lesions in these strains are approximately 20% linked by P1 transduction with a mutation in the rha gene, but are unlinked to ilv. Another mutation causing glutamine auxotrophy in strain JB674 is genetically distinct from the others. Strain JB674 grown in glucose medium containing ammonia as the nitrogen source has reduced levels of glutamine synthetase that is more adenylylated than in the parent strain, suggesting that the enzyme can not be deadenylylated normally. The lesion causing glutamine auxotrophy in JB674 lies in the region corresponding to the glnB and glnE genes affecting glutamine synthetase modification in Klebsiella areogenes. Four Gln+ revertants of JB674 have glutamine synthetase activities 4 to 6 fold higher than normal. One mutation causing this increased enzyme synthesis has been shown by three-factor crosses with the glnA mutations to lie near or within the glnA gene."}
{"id": "PMID:19345", "title": "[Bacterial recombination].", "content": "The most perspective trends in studying the mechanisms of genetic exchanges in bacteria are discussed. They are the following. 1. Comparison of the recombination stages in various biological phenomena such as transformation, transduction (generalized), conjugation (common and single-stranded) and transfection. 2. Characterization of genetic determinants and basic enzymes of the recombination process in Rec-systems of different bacteria. 3. Determination of some peculiar features of the intragenic recombination and finding a possible approach to their research. 4. Analysis of some plastic properties of the DNA structure and their application to the modern ideas in the formulation of a molecular mechanism of genetic recombination.", "contents": "[Bacterial recombination]. The most perspective trends in studying the mechanisms of genetic exchanges in bacteria are discussed. They are the following. 1. Comparison of the recombination stages in various biological phenomena such as transformation, transduction (generalized), conjugation (common and single-stranded) and transfection. 2. Characterization of genetic determinants and basic enzymes of the recombination process in Rec-systems of different bacteria. 3. Determination of some peculiar features of the intragenic recombination and finding a possible approach to their research. 4. Analysis of some plastic properties of the DNA structure and their application to the modern ideas in the formulation of a molecular mechanism of genetic recombination."}
{"id": "PMID:19346", "title": "Cimetidine and the gastric mucosal barrier.", "content": "The histamine H2-receptor antagonist, cimetidine, when given topically or parenterally, did not affect net luminal Na+ gain or net luminal H+ loss in vagally-denervated pouches of antrectomised dogs. Cimetidine did not affect disruption of the mucosal barrier by 5 mmol/l or 20 mmol/l sodium taurocholate.", "contents": "Cimetidine and the gastric mucosal barrier. The histamine H2-receptor antagonist, cimetidine, when given topically or parenterally, did not affect net luminal Na+ gain or net luminal H+ loss in vagally-denervated pouches of antrectomised dogs. Cimetidine did not affect disruption of the mucosal barrier by 5 mmol/l or 20 mmol/l sodium taurocholate."}
{"id": "PMID:19347", "title": "[Treatment of peptic ulcer with histamine H2 receptor antagonists].", "content": "Histamine H2-receptor antagonists (Burimamide, Metiamide and Cimetidine as the most recent generation) may drastically inhibit gastric acid secretion stimulated by histamine, pentagastrin, insulin, 2-deoxyglucose or an intragastrically instilled meal, respectively. This inhibitory action may explain the beneficial effects of H2-antagonists in the treatment of active peptic ulceration. On Cimetidine administered at a usual dosage over a 4--6 week period, serious side-effects must not be expected. At present studies aim to establish a Cimetidine dosage which, on long-term treatment, may reduce ulcer recurrency.", "contents": "[Treatment of peptic ulcer with histamine H2 receptor antagonists]. Histamine H2-receptor antagonists (Burimamide, Metiamide and Cimetidine as the most recent generation) may drastically inhibit gastric acid secretion stimulated by histamine, pentagastrin, insulin, 2-deoxyglucose or an intragastrically instilled meal, respectively. This inhibitory action may explain the beneficial effects of H2-antagonists in the treatment of active peptic ulceration. On Cimetidine administered at a usual dosage over a 4--6 week period, serious side-effects must not be expected. At present studies aim to establish a Cimetidine dosage which, on long-term treatment, may reduce ulcer recurrency."}
{"id": "PMID:19348", "title": "[Antacids and gastric mucosa. Protective effect of an antacid on acetylsalicylic acid induced functional lesions in the human gastric mucosa].", "content": "Salicylates do induce functional and morphological changes of the gastric mucosa: increased H+-back-diffusion, increased Na+-influx, and increased blood loss. Several functional parameters of the gastric mucosal barrier correlate with the transmural electrical potential difference (PD) which can be used as a sensitive, but unspecific parameter to detect functional changes of the gastric mucosal barrier. The effect of a salicylate alone and in presence of a liquid antiacid (Gastropulgit Gel) on transmural PD was measured in healthy volunteers. The presence of an antacid prevented the salicylate-induced drop of transmural PD. The tested antacid seems to exert a protective effect towards acute damage of the gastric mucosa induced by salicylates.", "contents": "[Antacids and gastric mucosa. Protective effect of an antacid on acetylsalicylic acid induced functional lesions in the human gastric mucosa]. Salicylates do induce functional and morphological changes of the gastric mucosa: increased H+-back-diffusion, increased Na+-influx, and increased blood loss. Several functional parameters of the gastric mucosal barrier correlate with the transmural electrical potential difference (PD) which can be used as a sensitive, but unspecific parameter to detect functional changes of the gastric mucosal barrier. The effect of a salicylate alone and in presence of a liquid antiacid (Gastropulgit Gel) on transmural PD was measured in healthy volunteers. The presence of an antacid prevented the salicylate-induced drop of transmural PD. The tested antacid seems to exert a protective effect towards acute damage of the gastric mucosa induced by salicylates."}
{"id": "PMID:19350", "title": "Interaction of colchicine with DNA molecules.", "content": "Colchicine (7.5 X 10-6M or 3.3 X 10-5M) was incubated at pH 7.0, 10.0, or 12.0 with high-molecular DNA from salmon sperm (7 X 10-5M or 3.5 X 10-5M DNA-P) at 40 degrees C. Interaction was monitored by UV spectrophotometry; Amax/Amin ratios, difference and additive spectra, and the quantity of colchicine bound to DNA were presented as functions of time, ionic strength and DNA concentration. Using NMR techniques, delta deltav 1/2/deltac values, chemical shifts and half-line widths of colchicine protons were analyzed as a function of the DNA/colchicine ratio, thus proving the interaction between alkaloid and DNA. An intercalation of the tropolone moiety of colchicine between the nitrogenous bases of DNA is suggested.", "contents": "Interaction of colchicine with DNA molecules. Colchicine (7.5 X 10-6M or 3.3 X 10-5M) was incubated at pH 7.0, 10.0, or 12.0 with high-molecular DNA from salmon sperm (7 X 10-5M or 3.5 X 10-5M DNA-P) at 40 degrees C. Interaction was monitored by UV spectrophotometry; Amax/Amin ratios, difference and additive spectra, and the quantity of colchicine bound to DNA were presented as functions of time, ionic strength and DNA concentration. Using NMR techniques, delta deltav 1/2/deltac values, chemical shifts and half-line widths of colchicine protons were analyzed as a function of the DNA/colchicine ratio, thus proving the interaction between alkaloid and DNA. An intercalation of the tropolone moiety of colchicine between the nitrogenous bases of DNA is suggested."}
{"id": "PMID:19351", "title": "Glutamine synthetase from pig brain: binding of adenosine triphosphate.", "content": "Glutamine synthetase was purified to homogeneity from fresh brain homogenates by a procedure that makes use of the affinity of this ATP requiring ligase to Cibacron 3G-A Blue-Sephadex G-75. It is shown that the interaction of pig brain enzyme with the dye does not concern the active centre but a non-catalytic although specific ATP binding site. Both sides contain a cysteine residue which may react with N-ethylmaleimide. The unprotected succinimidated enzyme is inactive, and aggregates. ATP alone protects only against aggregation, not against inactivation; the ATP/Mg2 complex also hinders inactivation. A tryptic heptadecapeptide isolated from the derivatized enzyme representing the carboxy terminal seems to belong to the active centre; its amino acid sequence was partially determined.", "contents": "Glutamine synthetase from pig brain: binding of adenosine triphosphate. Glutamine synthetase was purified to homogeneity from fresh brain homogenates by a procedure that makes use of the affinity of this ATP requiring ligase to Cibacron 3G-A Blue-Sephadex G-75. It is shown that the interaction of pig brain enzyme with the dye does not concern the active centre but a non-catalytic although specific ATP binding site. Both sides contain a cysteine residue which may react with N-ethylmaleimide. The unprotected succinimidated enzyme is inactive, and aggregates. ATP alone protects only against aggregation, not against inactivation; the ATP/Mg2 complex also hinders inactivation. A tryptic heptadecapeptide isolated from the derivatized enzyme representing the carboxy terminal seems to belong to the active centre; its amino acid sequence was partially determined."}
{"id": "PMID:19354", "title": "Enzymatically active peptide from the adenosine diphosphate-ribosylating toxin of Pseudomonas aeruginosa.", "content": "A nontoxic peptide (molecular weight, 26,000), which is active in catalyzing the adenosine diphosphate (ADP)-ribosylation of elongation factor 2, has been isolated from the culture supernatant of Pseudomonas aeruginosa strain 103 in stationary phase. Like fragment A from diphtheria toxin, the active peptide catalyzed the hydrolysis of nicotinamide adenine dinucleotide as well as the ADP-ribosylation of elongation factor 2 and showed similarities to fragment A in specific activity, kinetic constants, pH optimum, and ionic sensitivity. These results provide strong evidence for a high degree of homology in the structures of their active sites. That the peptide is not identical to fragment A is shown by the fact that it was not neutralized by fragment A-specific antiserum and was different in amino acid composition and pH and thermal labilities. Although definitive evidence is lacking, there are data suggesting that this peptide is a proteolytic fragment from the ADP-ribosylating toxin (exotoxin A; molecular weight, 66,000) produced by the same strain of P. aeruginosa.", "contents": "Enzymatically active peptide from the adenosine diphosphate-ribosylating toxin of Pseudomonas aeruginosa. A nontoxic peptide (molecular weight, 26,000), which is active in catalyzing the adenosine diphosphate (ADP)-ribosylation of elongation factor 2, has been isolated from the culture supernatant of Pseudomonas aeruginosa strain 103 in stationary phase. Like fragment A from diphtheria toxin, the active peptide catalyzed the hydrolysis of nicotinamide adenine dinucleotide as well as the ADP-ribosylation of elongation factor 2 and showed similarities to fragment A in specific activity, kinetic constants, pH optimum, and ionic sensitivity. These results provide strong evidence for a high degree of homology in the structures of their active sites. That the peptide is not identical to fragment A is shown by the fact that it was not neutralized by fragment A-specific antiserum and was different in amino acid composition and pH and thermal labilities. Although definitive evidence is lacking, there are data suggesting that this peptide is a proteolytic fragment from the ADP-ribosylating toxin (exotoxin A; molecular weight, 66,000) produced by the same strain of P. aeruginosa."}
{"id": "PMID:19355", "title": "Correlation between oral toxicity and in vitro stability of Clostridium botulinum type A and B toxins of different molecular sizes.", "content": "The in vitro sensitivity to acid and pepsin differed markedly among Clostridium botulinum type A and B toxins of different molecular sizes. The larger the molecular size of the toxin, the higher the resistance to these agents. Tye B derivative toxin was rapidly inactivated, but the progenitor toxins resisted in vitro exposure to rat intestinal juice. The molecular dissociation of the progenitor toxins did not occur in rat intestinal juice of pH 7.0, but did occur in a buffer solution of the same pH. The oral toxicity may depend mostly on the stability of toxin molecules in the stomach and, to a less extent, in the intestine. The present results seem to justify the conclusion that C. botulinum type A and B progenitor toxins with molecular sizes larger than 16S are more potent oral toxins than 12S progenitor toxins.", "contents": "Correlation between oral toxicity and in vitro stability of Clostridium botulinum type A and B toxins of different molecular sizes. The in vitro sensitivity to acid and pepsin differed markedly among Clostridium botulinum type A and B toxins of different molecular sizes. The larger the molecular size of the toxin, the higher the resistance to these agents. Tye B derivative toxin was rapidly inactivated, but the progenitor toxins resisted in vitro exposure to rat intestinal juice. The molecular dissociation of the progenitor toxins did not occur in rat intestinal juice of pH 7.0, but did occur in a buffer solution of the same pH. The oral toxicity may depend mostly on the stability of toxin molecules in the stomach and, to a less extent, in the intestine. The present results seem to justify the conclusion that C. botulinum type A and B progenitor toxins with molecular sizes larger than 16S are more potent oral toxins than 12S progenitor toxins."}
{"id": "PMID:19356", "title": "Effect of temperature on bacterial killing by serum and by polymorphonuclear leukocytes.", "content": "Bacterial killing by serum alone and by polymorphonuclear )PMN) leukocytes was studied at 37 degrees C and compared with killing at 39 and 41 degrees C. The test organisms for serum killing were Staphylococcus aureus 502A (serum resistant) and Escherichia coli O14 (serum sensitive). The organisms used in PMN killing tests were Streptococcus pneumoniae type 29 and E. coli O86.S aureus was not killed by serum alone at any temperature. Changes in temperature did not affect the rate of serum killing of E. coli O14 for the first 60 min, but by 90 and 120 min there was a discrepancy with continued killing at 37 degrees C, but no further killing at 39 and 41 degrees C. PMN phagocytic killing of the pneumococcus was enhanced at 39 degrees C compared with 37 degrees C, and phagocytic killing of E. coli O86 was decreased at 41 degrees C when compared with 37 degrees C. Therefore, it appears that under certain circumstances fever may aid the host PMNs in destroying organisms, whereas under other circumstances it may interfere with such destruction.", "contents": "Effect of temperature on bacterial killing by serum and by polymorphonuclear leukocytes. Bacterial killing by serum alone and by polymorphonuclear )PMN) leukocytes was studied at 37 degrees C and compared with killing at 39 and 41 degrees C. The test organisms for serum killing were Staphylococcus aureus 502A (serum resistant) and Escherichia coli O14 (serum sensitive). The organisms used in PMN killing tests were Streptococcus pneumoniae type 29 and E. coli O86.S aureus was not killed by serum alone at any temperature. Changes in temperature did not affect the rate of serum killing of E. coli O14 for the first 60 min, but by 90 and 120 min there was a discrepancy with continued killing at 37 degrees C, but no further killing at 39 and 41 degrees C. PMN phagocytic killing of the pneumococcus was enhanced at 39 degrees C compared with 37 degrees C, and phagocytic killing of E. coli O86 was decreased at 41 degrees C when compared with 37 degrees C. Therefore, it appears that under certain circumstances fever may aid the host PMNs in destroying organisms, whereas under other circumstances it may interfere with such destruction."}
{"id": "PMID:19357", "title": "Classical and alternative complement pathway activation by pneumococci.", "content": "Sixty-two strains of Streptococcus pneumoniae were studied for their abilities to consume selected components of classical and alternative complement pathways in human sera. The classical pathway was blocked by chelating calcium with ethyleneglycol-bios (beta-aminoethyl ether)-N,N-tetraacetic acid and by removing C4. The alternative pathway was blocked by removing factor B. Each strain's activation of the two pathways was compared with its nonimmune reactivity with the Fc region of immunoglobulin G (IgG). Activation of the classical complement pathway appeared to be independent of such Fc reactivity. Highly Fc-reactive strains, however, were shown to activate the alternative pathway more effectively than did less Fc-reactive strains. Since pneumococcal activation of the alternative pathway requires non-immunospecific IgG, these findings suggest that nonimmune binding of IgG on the pneumococcal surface endows it with complement-activating properties.", "contents": "Classical and alternative complement pathway activation by pneumococci. Sixty-two strains of Streptococcus pneumoniae were studied for their abilities to consume selected components of classical and alternative complement pathways in human sera. The classical pathway was blocked by chelating calcium with ethyleneglycol-bios (beta-aminoethyl ether)-N,N-tetraacetic acid and by removing C4. The alternative pathway was blocked by removing factor B. Each strain's activation of the two pathways was compared with its nonimmune reactivity with the Fc region of immunoglobulin G (IgG). Activation of the classical complement pathway appeared to be independent of such Fc reactivity. Highly Fc-reactive strains, however, were shown to activate the alternative pathway more effectively than did less Fc-reactive strains. Since pneumococcal activation of the alternative pathway requires non-immunospecific IgG, these findings suggest that nonimmune binding of IgG on the pneumococcal surface endows it with complement-activating properties."}
{"id": "PMID:19358", "title": "Inhibitory action of fatty acids on the growth of Neisseria gonorrhoeae.", "content": "Fatty acids of various chain lengths (C(1) to C(24)) were examined for their effects on growth, oxygen consumption, and in vitro reduced nicotinamide adenine dinucleotide oxidase activity of Neisseria gonorrhoeae CS-7. The growth inhibition caused by saturated fatty acids increased with increasing chain length to a maximum with palmitic acid (C(16)). Stearic acid (C(18)) and longer saturated fatty acids showed little inhibition of growth. However, unsaturated fatty acids of chain length C(16) to C(20) were inhibitory. Similar inhibition was observed with Bacillus subtilis and a deep rough mutant of Salmonella typhimurium. Wildtype S. typhimurium and Pseudomonas aeruginosa were more resistant to medium-chain (C(7) to C(10)) fatty acids and completely resistant to long-chain (C(12) to C(18)) fatty acids. Thus, sensitivity of N. gonorrhoeae to long-chain fatty acids appears to be related to the permeability of the outer membrane. Growth inhibition by short-chain (C(1) to C(6)) fatty acids was pH dependent; inhibition of growth increased with decreasing pH. Saturated fatty acids inhibited oxygen consumption by log-phase cells of N. gonorrhoeae. This inhibition increased with increasing chain length to a maximum observed with myristic acid (C(14)). Whereas stearic acid (C(18)) had little effect upon oxygen consumption, unsaturated C(18) fatty acids were inhibitory. An in vitro inhibition of reduced nicotinamide adenine dinucleotide oxidase activity by saturated (C(1) to C(12)) and unsaturated (C(16) to C(20)) fatty acids was also observed. Although the inhibitory concentrations were generally higher than those required to inhibit growth or oxygen consumption, an inhibition of electron transport may be partially responsible for the observed growth inhibition.", "contents": "Inhibitory action of fatty acids on the growth of Neisseria gonorrhoeae. Fatty acids of various chain lengths (C(1) to C(24)) were examined for their effects on growth, oxygen consumption, and in vitro reduced nicotinamide adenine dinucleotide oxidase activity of Neisseria gonorrhoeae CS-7. The growth inhibition caused by saturated fatty acids increased with increasing chain length to a maximum with palmitic acid (C(16)). Stearic acid (C(18)) and longer saturated fatty acids showed little inhibition of growth. However, unsaturated fatty acids of chain length C(16) to C(20) were inhibitory. Similar inhibition was observed with Bacillus subtilis and a deep rough mutant of Salmonella typhimurium. Wildtype S. typhimurium and Pseudomonas aeruginosa were more resistant to medium-chain (C(7) to C(10)) fatty acids and completely resistant to long-chain (C(12) to C(18)) fatty acids. Thus, sensitivity of N. gonorrhoeae to long-chain fatty acids appears to be related to the permeability of the outer membrane. Growth inhibition by short-chain (C(1) to C(6)) fatty acids was pH dependent; inhibition of growth increased with decreasing pH. Saturated fatty acids inhibited oxygen consumption by log-phase cells of N. gonorrhoeae. This inhibition increased with increasing chain length to a maximum observed with myristic acid (C(14)). Whereas stearic acid (C(18)) had little effect upon oxygen consumption, unsaturated C(18) fatty acids were inhibitory. An in vitro inhibition of reduced nicotinamide adenine dinucleotide oxidase activity by saturated (C(1) to C(12)) and unsaturated (C(16) to C(20)) fatty acids was also observed. Although the inhibitory concentrations were generally higher than those required to inhibit growth or oxygen consumption, an inhibition of electron transport may be partially responsible for the observed growth inhibition."}
{"id": "PMID:19359", "title": "Fungicidal properties of a chymotrypsin-like cationic protein from human neutrophils: adsorption to Candida parapsilosis.", "content": "Human neutrophils contain a chymotrypsin-like cationic protein (CLCP) that binds to the surface of Candida parapsilosis and is preferentially adsorbed by yeasts mixed with unfractionated extracts of neutrophil granules. Adsorption of CLCP to opsonized or nonopsonized yeasts was rapid at pH 4 through 8. Irreversible inhibition of the enzymatic site of CLCP by phenylmethylsulfonylfluoride or N-acetyl-Ala-Ala-Phe-chloromethyl ketone did not affect its adsorption by yeast. Adsorption, highly sensitive to ionic strength, was abrogated by 0.15 M KCl. The number of CLCP molecules adsorbed per yeast cell and the loss of colony-forming units are described by an exponential relationship.", "contents": "Fungicidal properties of a chymotrypsin-like cationic protein from human neutrophils: adsorption to Candida parapsilosis. Human neutrophils contain a chymotrypsin-like cationic protein (CLCP) that binds to the surface of Candida parapsilosis and is preferentially adsorbed by yeasts mixed with unfractionated extracts of neutrophil granules. Adsorption of CLCP to opsonized or nonopsonized yeasts was rapid at pH 4 through 8. Irreversible inhibition of the enzymatic site of CLCP by phenylmethylsulfonylfluoride or N-acetyl-Ala-Ala-Phe-chloromethyl ketone did not affect its adsorption by yeast. Adsorption, highly sensitive to ionic strength, was abrogated by 0.15 M KCl. The number of CLCP molecules adsorbed per yeast cell and the loss of colony-forming units are described by an exponential relationship."}
{"id": "PMID:19360", "title": "Activation of botulinum toxins in the absence of nicking.", "content": "The derivative toxins purified from cultures of proteolytic strains of Clostridium botulinum types A and F were found to have been only partially nicked but were fully activated. Trypsinization of C. botulinum type B derivative toxin at pH 6.0 resulted in simultaneous activation and nicking, whereas at pH 4.5, activation preceded nicking. The toxin was split by trypsin at pH 6.0 into two fragments with molecular weights of 112, ooo and 57,000. The toxin contained at least three trypsin-sensitive peptide bonds, one of which was more sensitive than the others at pH 6.0. These results indicate that activation of botulinum toxins by trypsin or endogenous protease (s) is not a direct result of nicking.", "contents": "Activation of botulinum toxins in the absence of nicking. The derivative toxins purified from cultures of proteolytic strains of Clostridium botulinum types A and F were found to have been only partially nicked but were fully activated. Trypsinization of C. botulinum type B derivative toxin at pH 6.0 resulted in simultaneous activation and nicking, whereas at pH 4.5, activation preceded nicking. The toxin was split by trypsin at pH 6.0 into two fragments with molecular weights of 112, ooo and 57,000. The toxin contained at least three trypsin-sensitive peptide bonds, one of which was more sensitive than the others at pH 6.0. These results indicate that activation of botulinum toxins by trypsin or endogenous protease (s) is not a direct result of nicking."}
{"id": "PMID:19362", "title": "Action of atropine on histamine-induced bronchoconstriction in asthmatic children. A pharmacocapnographic study.", "content": "In their earlier methodological model studies the authors confirmed the protective effect of atropine in inhalative acetylcholine provocation. In the present work the role of parasympatholysis is investigated in histamine-induced bronchospasm by the method. It was found that a protective effect was exerted in histamine provocation repeated 20 minutes after subcutaneous administration of atropine sulphate in a dose of 0.01 mg/kg. The protective effect proved independent of the individual histamine sensitivities of the patients. The initial value of the CO2 curve prior to provocation was not improved.", "contents": "Action of atropine on histamine-induced bronchoconstriction in asthmatic children. A pharmacocapnographic study. In their earlier methodological model studies the authors confirmed the protective effect of atropine in inhalative acetylcholine provocation. In the present work the role of parasympatholysis is investigated in histamine-induced bronchospasm by the method. It was found that a protective effect was exerted in histamine provocation repeated 20 minutes after subcutaneous administration of atropine sulphate in a dose of 0.01 mg/kg. The protective effect proved independent of the individual histamine sensitivities of the patients. The initial value of the CO2 curve prior to provocation was not improved."}
{"id": "PMID:19364", "title": "Thin-layer and gas-liquid chromatographic procedures for the determination of perazine and its metabolites in human body fluids.", "content": "The quantitative determination of perazine, a neuroleptic drug, and its metabolites in body fluids is difficult in view of the low concentrations to be expected under therapeutic conditions as well as of the problem of convenient detectors. Different methods for extraction and measurement of perazine concentration in blood samples are discussed, with special consideration of partition coefficients and the properties of the chromatographic systems (thin-layer and gas-liquid chromatography). A new and simple method for rapid gas chromatographic determination of perazine is presented.", "contents": "Thin-layer and gas-liquid chromatographic procedures for the determination of perazine and its metabolites in human body fluids. The quantitative determination of perazine, a neuroleptic drug, and its metabolites in body fluids is difficult in view of the low concentrations to be expected under therapeutic conditions as well as of the problem of convenient detectors. Different methods for extraction and measurement of perazine concentration in blood samples are discussed, with special consideration of partition coefficients and the properties of the chromatographic systems (thin-layer and gas-liquid chromatography). A new and simple method for rapid gas chromatographic determination of perazine is presented."}
{"id": "PMID:19365", "title": "A model for distinguishing between beta1-receptors which mediate a specific effect on the heart rate and those which mediate a positively inotropic effect.", "content": "The study was conducted in six healthy male volunteers aged between 20 and 30 years. Cardiac output was determined by means of the Swan-Ganz-thermodilution-method. A control-study was carried out, during which an isoproterenolinfusion with increasing doses was given. Fifty minutes after i.v. injection of a beta-receptor-blocker the hemodynamic parameters were measured again under increasing doses of isoproterenol until the block was overcome. This study procedure was performed twice in each subject at an interval of at least 14 days. For the one study 15 mg propranolol i.v. and for the other 0,5 mg mepindolol i.v., a new beta-receptor-blocker, were injected. After i.v. injection of propranolol the dose-response-relationship-curve for the heart-rate (HR) and stroke volume (SV) describes a definite shift to the right. After mepindolol the dose-effect curve for the heart rate describes a definite shift to the right, as seen with propranolol. In contrast, only a very slight shift can be seen in respect of the SV increase, i.e. the SV and HR curves dissociate under mepindolol. The results of our study indicate, that a distinction can be made with respect to the so-called beta 1-receptors between those mediating a specific effect on the heart-rate and those mediating a mainly positive inotropic effect.", "contents": "A model for distinguishing between beta1-receptors which mediate a specific effect on the heart rate and those which mediate a positively inotropic effect. The study was conducted in six healthy male volunteers aged between 20 and 30 years. Cardiac output was determined by means of the Swan-Ganz-thermodilution-method. A control-study was carried out, during which an isoproterenolinfusion with increasing doses was given. Fifty minutes after i.v. injection of a beta-receptor-blocker the hemodynamic parameters were measured again under increasing doses of isoproterenol until the block was overcome. This study procedure was performed twice in each subject at an interval of at least 14 days. For the one study 15 mg propranolol i.v. and for the other 0,5 mg mepindolol i.v., a new beta-receptor-blocker, were injected. After i.v. injection of propranolol the dose-response-relationship-curve for the heart-rate (HR) and stroke volume (SV) describes a definite shift to the right. After mepindolol the dose-effect curve for the heart rate describes a definite shift to the right, as seen with propranolol. In contrast, only a very slight shift can be seen in respect of the SV increase, i.e. the SV and HR curves dissociate under mepindolol. The results of our study indicate, that a distinction can be made with respect to the so-called beta 1-receptors between those mediating a specific effect on the heart-rate and those mediating a mainly positive inotropic effect."}
{"id": "PMID:19366", "title": "Explanation of the observation of pancreatic ribonuclease activity at pH 4.5.", "content": "A recent conclusion that beef pancreas contained a molecular species of ribonuclease with intrinsically high activity at pH 4.5 has been found to be incorrect. The particular assay used in the earlier experiments gives anomalous results at acid pH in the presence of low concentrations of ions such as phosphate which was used during the fractionation. By turning to the more widely employed form of the  perchloric acid precipitation assay, interference is avoided and the ribonuclease in beef pancreas is confirmed as consisting almost completely of the molecular species well-characterized as ribonuclease A. The clarification of the assay question permits a clear interpretation of the results of each step of the chromatographic purification procedure that led to the initial conclusion, including an artifact that arose when gel filtration was attempted with distilled water rather than with buffer.", "contents": "Explanation of the observation of pancreatic ribonuclease activity at pH 4.5. A recent conclusion that beef pancreas contained a molecular species of ribonuclease with intrinsically high activity at pH 4.5 has been found to be incorrect. The particular assay used in the earlier experiments gives anomalous results at acid pH in the presence of low concentrations of ions such as phosphate which was used during the fractionation. By turning to the more widely employed form of the  perchloric acid precipitation assay, interference is avoided and the ribonuclease in beef pancreas is confirmed as consisting almost completely of the molecular species well-characterized as ribonuclease A. The clarification of the assay question permits a clear interpretation of the results of each step of the chromatographic purification procedure that led to the initial conclusion, including an artifact that arose when gel filtration was attempted with distilled water rather than with buffer."}
{"id": "PMID:19367", "title": "Association-dissociation and denaturation behaviour of an oligomeric seed protein alpha-globulin of Sesamum indicum L. in acid and alkaline solutions.", "content": "The association-dissociation and denaturation behaviour of the major protein fraction, alpha-globulin of sesame seed (Sesamum indicum L.), in acid and alkaline solutions in the ranges of pH 4.2-1.5 and pH 7-12 have been studied. The results of gel filtration, fluorescence and viscosity measurements indicate dissociation and denaturation of the protein up to pH approximately 3. The difference spectrum in this region arises from a combination of dissociation, denaturation and charge effect on the chromophore. In still stronger acid solution, reassociation of the dissociated fraction takes place by hydrophobic interaction. In alkaline solution dissociation takes place around pH 8, and above pH 10 dissociation and denaturation proceed simultaneously as has been evidenced by sedimentation, fluorescence, spectral change, optical rotation and viscosity measurements. The phenolic group (pKInt=10.6) in the protein is abnormal and denaturation in alkaline solution is irreversible. Above pH 11.5 further dissociation of the protein takes place. Characteristic pH values of transition from 10.6-10.8 indicate that the transition of the protein involves a single step in alkaline solution.", "contents": "Association-dissociation and denaturation behaviour of an oligomeric seed protein alpha-globulin of Sesamum indicum L. in acid and alkaline solutions. The association-dissociation and denaturation behaviour of the major protein fraction, alpha-globulin of sesame seed (Sesamum indicum L.), in acid and alkaline solutions in the ranges of pH 4.2-1.5 and pH 7-12 have been studied. The results of gel filtration, fluorescence and viscosity measurements indicate dissociation and denaturation of the protein up to pH approximately 3. The difference spectrum in this region arises from a combination of dissociation, denaturation and charge effect on the chromophore. In still stronger acid solution, reassociation of the dissociated fraction takes place by hydrophobic interaction. In alkaline solution dissociation takes place around pH 8, and above pH 10 dissociation and denaturation proceed simultaneously as has been evidenced by sedimentation, fluorescence, spectral change, optical rotation and viscosity measurements. The phenolic group (pKInt=10.6) in the protein is abnormal and denaturation in alkaline solution is irreversible. Above pH 11.5 further dissociation of the protein takes place. Characteristic pH values of transition from 10.6-10.8 indicate that the transition of the protein involves a single step in alkaline solution."}
{"id": "PMID:19368", "title": "Fluorescent labelling of 6-phosphogluconate dehydrogenase from Bacillus stearothermophilus.", "content": "The thermophilic 6-phosphogluconate dehydrogenase from Bacillus stearothermophilus was inhibited upon specific modification of the -SH group of cysteine residues by 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-Cl) at pH 7.0. By using 20-100-fold molar excess of NBD-CL the reaction occurs slowly at pH 7.0 as a first order process. Partial protection from inactivation was observed when the substrate 6-phosphogluconate or the coenzyme NADP was added to the reaction mixture. Complete inactivation was achieved upon modification of 1.9 of the six cysteine residues per mole of enzyme, which corresponds to nearly one residue per enzyme subunit. Circular dichroism measurements suggest that the gross structure of the protein molecule is practically unchanged upon reaction of the enzyme with NBD-Cl. Melting profile experiments revealed a single transition occurring at about 65 degrees C. Analogously, the profile of intensity of the fluorescence emission at 520 nm of the enzyme-bound S-NBD groups versus temperature indicated a midpoint of transition near 65 degrees C. Since this melting temperature corresponds closely to that observed with the native enzyme, these results would indicate that the molecular organizations of the native and modified enzyme are similar and stabilized by similar interactions within the polypeptide chain.", "contents": "Fluorescent labelling of 6-phosphogluconate dehydrogenase from Bacillus stearothermophilus. The thermophilic 6-phosphogluconate dehydrogenase from Bacillus stearothermophilus was inhibited upon specific modification of the -SH group of cysteine residues by 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-Cl) at pH 7.0. By using 20-100-fold molar excess of NBD-CL the reaction occurs slowly at pH 7.0 as a first order process. Partial protection from inactivation was observed when the substrate 6-phosphogluconate or the coenzyme NADP was added to the reaction mixture. Complete inactivation was achieved upon modification of 1.9 of the six cysteine residues per mole of enzyme, which corresponds to nearly one residue per enzyme subunit. Circular dichroism measurements suggest that the gross structure of the protein molecule is practically unchanged upon reaction of the enzyme with NBD-Cl. Melting profile experiments revealed a single transition occurring at about 65 degrees C. Analogously, the profile of intensity of the fluorescence emission at 520 nm of the enzyme-bound S-NBD groups versus temperature indicated a midpoint of transition near 65 degrees C. Since this melting temperature corresponds closely to that observed with the native enzyme, these results would indicate that the molecular organizations of the native and modified enzyme are similar and stabilized by similar interactions within the polypeptide chain."}
{"id": "PMID:19369", "title": "The possible role of dopamine in phenothiazine-induced hypothermia in rats: an application to DA hypothesis of schizophrenia.", "content": "Hypothermic effects of d-Amphetamine, chlorpromazine, a variety of other phenothiazines, ET495 and haloperidol in rats at 4 degrees C were measured separately and in combination. All the drugs produced some hypothermia. Among the phenothiazines, degree of hypothermia induced was found to be correlated with relative effectiveness of the drug as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetadrugs as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetamine was greater than for either drug alone. Hypothermic effects of the combination CPZ with Amphetamine was potentiated by haloperidol but blocked by ET495. The evidence supports a model of neuronal feedback loops either within the central DA mesolimbic pathway or between the mesolimbic and nigrostriatal DA systems. The establishment of interdependency between antipsychotic and hypothermic effects of phenothiazines offers promise not only to a greater understanding of the mechanisms underlying these effects, but the possibility of an objective test for screening new materials for antipsychotic effectiveness.", "contents": "The possible role of dopamine in phenothiazine-induced hypothermia in rats: an application to DA hypothesis of schizophrenia. Hypothermic effects of d-Amphetamine, chlorpromazine, a variety of other phenothiazines, ET495 and haloperidol in rats at 4 degrees C were measured separately and in combination. All the drugs produced some hypothermia. Among the phenothiazines, degree of hypothermia induced was found to be correlated with relative effectiveness of the drug as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetadrugs as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetamine was greater than for either drug alone. Hypothermic effects of the combination CPZ with Amphetamine was potentiated by haloperidol but blocked by ET495. The evidence supports a model of neuronal feedback loops either within the central DA mesolimbic pathway or between the mesolimbic and nigrostriatal DA systems. The establishment of interdependency between antipsychotic and hypothermic effects of phenothiazines offers promise not only to a greater understanding of the mechanisms underlying these effects, but the possibility of an objective test for screening new materials for antipsychotic effectiveness."}
{"id": "PMID:19370", "title": "WIN 27,147-2 in the treatment of depression. An uncontrolled clinical study.", "content": "An uncontrolled clinical study with WIN 27,147-2 was conducted with 10 hospitalized depressed psychiatric patients. There was statistically significant improvement in the total scores of the HAM-D, BPRS and Zung; in the scores of all the factors of the HAM-D and Zung; in the scores of the anxiety/depression and activation factors of the BPRS, and in the scores of 6 of the 18 items of the BPRS. Judged by clinical global impression, 9 of the 10 patients were very much improved and 1 patient much improved. The most frequently occurring adverse effects were dry mouth, sweating, drowsiness and insomnia.", "contents": "WIN 27,147-2 in the treatment of depression. An uncontrolled clinical study. An uncontrolled clinical study with WIN 27,147-2 was conducted with 10 hospitalized depressed psychiatric patients. There was statistically significant improvement in the total scores of the HAM-D, BPRS and Zung; in the scores of all the factors of the HAM-D and Zung; in the scores of the anxiety/depression and activation factors of the BPRS, and in the scores of 6 of the 18 items of the BPRS. Judged by clinical global impression, 9 of the 10 patients were very much improved and 1 patient much improved. The most frequently occurring adverse effects were dry mouth, sweating, drowsiness and insomnia."}
{"id": "PMID:19375", "title": "Some properties of hemoglobin Gun Hill.", "content": "Hb Gun Hill has been found in an asymptomatic black female living in Alabama; neither her parents nor her two siblings carry the variant. The deletion of five amino acid residues in the beta chain of Hb Gun Hill (alpha2beta2 91-95 deleted) causes this variant to have a high oxygen affinity, an interaction coefficient of unity and an absence of the Bohr effect. The rate of oxidation of liganded Hb Gun Hill by the ferricyanide ion follows first-order kinetics. Hb Gun Hill is to a great extent dissociated into dimers over a wide range of pH values.", "contents": "Some properties of hemoglobin Gun Hill. Hb Gun Hill has been found in an asymptomatic black female living in Alabama; neither her parents nor her two siblings carry the variant. The deletion of five amino acid residues in the beta chain of Hb Gun Hill (alpha2beta2 91-95 deleted) causes this variant to have a high oxygen affinity, an interaction coefficient of unity and an absence of the Bohr effect. The rate of oxidation of liganded Hb Gun Hill by the ferricyanide ion follows first-order kinetics. Hb Gun Hill is to a great extent dissociated into dimers over a wide range of pH values."}
{"id": "PMID:19376", "title": "A test tube method for quantitation of hemoglobin A2 using DE 52 cellulose.", "content": "A test tube method for quantitation of Hb A2 which is an adaption of the microcolumn chromatographic method is described. The method uses microangular DEAE cellulose (DE 52, microgranular and preswollen, Whatman Inc.) equilibrated with a 0.2 M glycine-0.1% KCN solution, pH 7.25. Hemoglobin A and F become bound to the resin while Hb A2 is in supernatant fraction allowing its quantitation. The method is simple, rapid, inexpensive and accurate, and allows one technician to determine the level of Hb A2 in at least 50 samples a day. The method can be used with whole blood, hemolysates and blood collected on filter paper.", "contents": "A test tube method for quantitation of hemoglobin A2 using DE 52 cellulose. A test tube method for quantitation of Hb A2 which is an adaption of the microcolumn chromatographic method is described. The method uses microangular DEAE cellulose (DE 52, microgranular and preswollen, Whatman Inc.) equilibrated with a 0.2 M glycine-0.1% KCN solution, pH 7.25. Hemoglobin A and F become bound to the resin while Hb A2 is in supernatant fraction allowing its quantitation. The method is simple, rapid, inexpensive and accurate, and allows one technician to determine the level of Hb A2 in at least 50 samples a day. The method can be used with whole blood, hemolysates and blood collected on filter paper."}
{"id": "PMID:19373", "title": "The effect of different endotracheal suction procedures on arterial blood gases in a controlled experimental model.", "content": "In an anesthetized hypoxemic animal model, 15 seconds of endotracheal suctioning, using a suction pressure of --170 mm. Hg and endotracheal tube to suction catheter ratio of 1.87 to 1, produced a 13 mm. Hg fall in arterial oxygen tension. Oxygen tension did not return to control level even at 5 minutes after suctioning. Giving 100 per cent oxygen before suctioning prevented suction-induced hypoxemia during and immediately after suctioning, but at 5 minutes after suctioning, oxygen tension fell below control levels. Mechanical lung hyperinflation with room air after suctioning quickly raised arterial oxygen tension above control levels. When mechanical ventilation using 100 per cent oxygen was maintained before, during, and after the suction procedure, arterial oxygen tension remained elevated at all times.", "contents": "The effect of different endotracheal suction procedures on arterial blood gases in a controlled experimental model. In an anesthetized hypoxemic animal model, 15 seconds of endotracheal suctioning, using a suction pressure of --170 mm. Hg and endotracheal tube to suction catheter ratio of 1.87 to 1, produced a 13 mm. Hg fall in arterial oxygen tension. Oxygen tension did not return to control level even at 5 minutes after suctioning. Giving 100 per cent oxygen before suctioning prevented suction-induced hypoxemia during and immediately after suctioning, but at 5 minutes after suctioning, oxygen tension fell below control levels. Mechanical lung hyperinflation with room air after suctioning quickly raised arterial oxygen tension above control levels. When mechanical ventilation using 100 per cent oxygen was maintained before, during, and after the suction procedure, arterial oxygen tension remained elevated at all times."}
{"id": "PMID:19377", "title": "Isolation of high oxygen affinity hemoglobins.", "content": "This paper describes a method for isolating high oxygen affinity hemoglobins. It involves the selective derivatisation of the cysteine residue at position 93 in the beta chain. The iodoacetamide derivative of the high oxygen affinity hemoglobin was separated from the more negatively charged iodoacetic acid derivative of HbA on DEAE-Sephadex. The method was used to isolate two high oxygen affinity hemoglobins, one of which was subsequently identified as Hb Heathrow.", "contents": "Isolation of high oxygen affinity hemoglobins. This paper describes a method for isolating high oxygen affinity hemoglobins. It involves the selective derivatisation of the cysteine residue at position 93 in the beta chain. The iodoacetamide derivative of the high oxygen affinity hemoglobin was separated from the more negatively charged iodoacetic acid derivative of HbA on DEAE-Sephadex. The method was used to isolate two high oxygen affinity hemoglobins, one of which was subsequently identified as Hb Heathrow."}
{"id": "PMID:19380", "title": "The activity and distribution of gamma-glutamyl transpeptidase (y-GT) in human lung cancers serially transplanted in nude mice.", "content": "Gamma-glutamyl transpeptidase (y-GT) activity and distribution were investigated in different types of human lung cancers (three epidermoid carcinomas, one large cell carcinoma) which were maintained by serial transplantation in nude mice. All transplanted tumour fragments were positive for the enzyme. In the epidermoid carcinomas, y-GT levels were related to the degree of tumour differentiation. Enzyme activity in tumour fragments was always higher than that found in normal adult human lung tissue, and was, in general, maintained throughout the transplantation series.", "contents": "The activity and distribution of gamma-glutamyl transpeptidase (y-GT) in human lung cancers serially transplanted in nude mice. Gamma-glutamyl transpeptidase (y-GT) activity and distribution were investigated in different types of human lung cancers (three epidermoid carcinomas, one large cell carcinoma) which were maintained by serial transplantation in nude mice. All transplanted tumour fragments were positive for the enzyme. In the epidermoid carcinomas, y-GT levels were related to the degree of tumour differentiation. Enzyme activity in tumour fragments was always higher than that found in normal adult human lung tissue, and was, in general, maintained throughout the transplantation series."}
{"id": "PMID:19408", "title": "Fortimicins A and B, new aminoglycoside antibiotics. II. Isolation, physico-chemical and chromatographic properties.", "content": "The aminoglycoside antibiotics fortimicins A and B produced by a naturally occurring strain Micromonospora sp. MK-70 were isolated from its fermentation beer. Fortimicins A and B were isolated as water-soluble, basic, white amorphous powders having molecular formula C17H35N5O6 and C15H32N4O5, respectively. Acid hydrolysis of fortimicin A indicated that it has one mole of glycine in its molecule while fortimicin B has not. Paper chromatography, silica-gel and carbon thin-layer chromatography revealed that fortimicins A and B are novel aminoglycoside antibiotics.", "contents": "Fortimicins A and B, new aminoglycoside antibiotics. II. Isolation, physico-chemical and chromatographic properties. The aminoglycoside antibiotics fortimicins A and B produced by a naturally occurring strain Micromonospora sp. MK-70 were isolated from its fermentation beer. Fortimicins A and B were isolated as water-soluble, basic, white amorphous powders having molecular formula C17H35N5O6 and C15H32N4O5, respectively. Acid hydrolysis of fortimicin A indicated that it has one mole of glycine in its molecule while fortimicin B has not. Paper chromatography, silica-gel and carbon thin-layer chromatography revealed that fortimicins A and B are novel aminoglycoside antibiotics."}
{"id": "PMID:19409", "title": "Fortimicins A and B, new aminoglycoside antibiotics. IV. In vitro study of fortimicin A compared with other aminoglycosides.", "content": "The in vitro antimicrobial activity of fortimicin A, the most active member of the fortimicin complex, was compared with that of amikacin, gentamicin, sagamicin and tobramycin against 352 strains of Enterobacteriaceae and other medically significant organisms. Against most of these organisms fortimicin and amikacin had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin, sagamicin or tobramycin. Fortimicin had relatively weak activity against Pseudomonas aeruginosa strains. Fortimicin shows many of the characteristics of other aminoglycoside antibiotics: (i) improved activity at alkaline pH, (ii) rapid, bactericidal action, (iii) reduced activity with increasing inoculum levels, and (iv) synergistic activity with penicillin against enterococci. The activity of fortimicin was compared to that of gentamicin, tobramycin and amikacin against a group of 95 naturally occurring, antibiotic-resistant Gram-negative bacilli other than Pseudomonas. The organisms were isolated from clinical sources and selected primarily for gentamicin resistance by the sensitivity disc test. Fortimicin showed excellent activity against this group of organisms. At a concentration of 6.2 mcg/ml, fortimicin inhibited the most strains (92.6%) followed by amikacin (90.5%), gentamicin (23.2%) and tobramycin (8.4%).", "contents": "Fortimicins A and B, new aminoglycoside antibiotics. IV. In vitro study of fortimicin A compared with other aminoglycosides. The in vitro antimicrobial activity of fortimicin A, the most active member of the fortimicin complex, was compared with that of amikacin, gentamicin, sagamicin and tobramycin against 352 strains of Enterobacteriaceae and other medically significant organisms. Against most of these organisms fortimicin and amikacin had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin, sagamicin or tobramycin. Fortimicin had relatively weak activity against Pseudomonas aeruginosa strains. Fortimicin shows many of the characteristics of other aminoglycoside antibiotics: (i) improved activity at alkaline pH, (ii) rapid, bactericidal action, (iii) reduced activity with increasing inoculum levels, and (iv) synergistic activity with penicillin against enterococci. The activity of fortimicin was compared to that of gentamicin, tobramycin and amikacin against a group of 95 naturally occurring, antibiotic-resistant Gram-negative bacilli other than Pseudomonas. The organisms were isolated from clinical sources and selected primarily for gentamicin resistance by the sensitivity disc test. Fortimicin showed excellent activity against this group of organisms. At a concentration of 6.2 mcg/ml, fortimicin inhibited the most strains (92.6%) followed by amikacin (90.5%), gentamicin (23.2%) and tobramycin (8.4%)."}
{"id": "PMID:19410", "title": "Aminoglycoside nephrotoxicity. I. Effects of aminoglycoside antibiotics on iodohippurate accumulation in rabbit renal cortical slices.", "content": "The effects of aminoglycoside antibiotics on the accumulation of O-125I-hippurate (OIH) in rabbit renal cortical slices were assessed in an attempt to establish an in vitro model for aminoglycoside nephrotoxicity. Accumulation of OIH was measured after incubation of cortex slices in media containing aminoglycosides in different concentrations. All aminoglycosides depressed OIH accumulation in the following minimum concentrations: Dihydrostreptomycin and kanamycin, 2,000 microgram/ml (P less than 0.01); streptomycin and neomycin, 1,000 microgram/ml (P less than 0.05 and P less than 0.01); amikacin and tobramycin, 300 microgram/ml (P less than 0.05); gentamicin, 100 microgram/ml (P less than 0.05). A concentration of 2,000 microgram/ml caused the following reduction in OIH accumulation: Dihydrostreptomycin, 19.3%; streptomycin, 28.9%; kanamycin, 23.8%; neomycin, 62.5%; gentamicin, 68.0%; amikacin and tobramycin, 100%. Changes in pH of the incubation media after addition of aminoglycosides were only partially responsible for the observed depression of OIH accumulation and there was no evidence of substrate competition between aminoglycosides and OIH. The in vitro model described here appears to be inadequate as a sole predictor of aminoglycoside nephrotoxicity, but may provide a supplementary tool in the investigation of aminoglycoside proximal tubular cell toxicity.", "contents": "Aminoglycoside nephrotoxicity. I. Effects of aminoglycoside antibiotics on iodohippurate accumulation in rabbit renal cortical slices. The effects of aminoglycoside antibiotics on the accumulation of O-125I-hippurate (OIH) in rabbit renal cortical slices were assessed in an attempt to establish an in vitro model for aminoglycoside nephrotoxicity. Accumulation of OIH was measured after incubation of cortex slices in media containing aminoglycosides in different concentrations. All aminoglycosides depressed OIH accumulation in the following minimum concentrations: Dihydrostreptomycin and kanamycin, 2,000 microgram/ml (P less than 0.01); streptomycin and neomycin, 1,000 microgram/ml (P less than 0.05 and P less than 0.01); amikacin and tobramycin, 300 microgram/ml (P less than 0.05); gentamicin, 100 microgram/ml (P less than 0.05). A concentration of 2,000 microgram/ml caused the following reduction in OIH accumulation: Dihydrostreptomycin, 19.3%; streptomycin, 28.9%; kanamycin, 23.8%; neomycin, 62.5%; gentamicin, 68.0%; amikacin and tobramycin, 100%. Changes in pH of the incubation media after addition of aminoglycosides were only partially responsible for the observed depression of OIH accumulation and there was no evidence of substrate competition between aminoglycosides and OIH. The in vitro model described here appears to be inadequate as a sole predictor of aminoglycoside nephrotoxicity, but may provide a supplementary tool in the investigation of aminoglycoside proximal tubular cell toxicity."}
{"id": "PMID:19413", "title": "Role of tissue hypermetabolism in stimulation of ventilation by dinitrophenol.", "content": "Several authors have hypothesized that tissue hypermetabolism accounts for increases in ventilation (VE) elicited by 2,4-dinitrophenol. However, some data in the literature indicate that stimulation of VE by isomers of dinitrophenol is unrelated to tissue metabolic rate. To test this latter concept, we compared three different isomers of dinitrophenol (i.e., 2,4-dinitrophenol (2,4-DNP), 2,5-dinitrophenol (2,5,-DNP), 2,6-dinitrophenol (2,6-DNP) with respect to stimulation of VE and with respect to stimulation of oxygen consumption (VO2). In all experiments, 3-4 mg/kg of one dinitrophenol isomer was administered to chloralose anesthetized dogs by intra-arterial infusion. 2,4-DNP elicited large increments in both VE and VO2, 2,6-DNP elicited moderate increments in both VE and VO2, whereas 2,5-DNP elicited small increments in both VE and VO2. These observations demonstrate a correlation between ventilatory and metabolic changes affected by isomers of dinitrophenol. Accordingly, these results are consistent with the hypothesis that ventilatory stimulation by congeners of dinitrophenol is related to tissue hypermetabolism.", "contents": "Role of tissue hypermetabolism in stimulation of ventilation by dinitrophenol. Several authors have hypothesized that tissue hypermetabolism accounts for increases in ventilation (VE) elicited by 2,4-dinitrophenol. However, some data in the literature indicate that stimulation of VE by isomers of dinitrophenol is unrelated to tissue metabolic rate. To test this latter concept, we compared three different isomers of dinitrophenol (i.e., 2,4-dinitrophenol (2,4-DNP), 2,5-dinitrophenol (2,5,-DNP), 2,6-dinitrophenol (2,6-DNP) with respect to stimulation of VE and with respect to stimulation of oxygen consumption (VO2). In all experiments, 3-4 mg/kg of one dinitrophenol isomer was administered to chloralose anesthetized dogs by intra-arterial infusion. 2,4-DNP elicited large increments in both VE and VO2, 2,6-DNP elicited moderate increments in both VE and VO2, whereas 2,5-DNP elicited small increments in both VE and VO2. These observations demonstrate a correlation between ventilatory and metabolic changes affected by isomers of dinitrophenol. Accordingly, these results are consistent with the hypothesis that ventilatory stimulation by congeners of dinitrophenol is related to tissue hypermetabolism."}
{"id": "PMID:19414", "title": "Column chromatographic analysis of barbiturates in their dosage forms. IV. Combinations with parabens.", "content": "The nature of the alkaline hydrolysis of some barbiturates in combinations with parabens (p-hydroxybenzoates) was studied with controlled variables, including temperature, viscosity, and concentrations of sodium hydroxide, barbiturate, and parabens. The kinetic studies showed that parabens could be completely hydrolyzed in strong base at 40 degrees C in 1 hr, while the barbiturate remained intact and was readily isolated by partition chromatography, Based on the theoretical results, a partition chromatographic procedure for butabarbital with parabens was devised. Standard recoveries averaged 100.7% with a standard deviation of 0.89. Kinetic data indicate that the hydrolysis of parabens could also be applied to analyze combinations with amo-, seco-, and pentobarbitals. Phenobarbital and parabens are readily separated by partition chromatographic methods without prior hydrolysis of the parabens. The low extraction constant for phenobarbital allowed its retention on a column against relatively strong solvents while the intact parabens are eluted. A slightly modified method was applied to the separation of phenobarbital from parabens. Standard recoveries average 99.9% with a standard deviation of 0.69.", "contents": "Column chromatographic analysis of barbiturates in their dosage forms. IV. Combinations with parabens. The nature of the alkaline hydrolysis of some barbiturates in combinations with parabens (p-hydroxybenzoates) was studied with controlled variables, including temperature, viscosity, and concentrations of sodium hydroxide, barbiturate, and parabens. The kinetic studies showed that parabens could be completely hydrolyzed in strong base at 40 degrees C in 1 hr, while the barbiturate remained intact and was readily isolated by partition chromatography, Based on the theoretical results, a partition chromatographic procedure for butabarbital with parabens was devised. Standard recoveries averaged 100.7% with a standard deviation of 0.89. Kinetic data indicate that the hydrolysis of parabens could also be applied to analyze combinations with amo-, seco-, and pentobarbitals. Phenobarbital and parabens are readily separated by partition chromatographic methods without prior hydrolysis of the parabens. The low extraction constant for phenobarbital allowed its retention on a column against relatively strong solvents while the intact parabens are eluted. A slightly modified method was applied to the separation of phenobarbital from parabens. Standard recoveries average 99.9% with a standard deviation of 0.69."}
{"id": "PMID:19415", "title": "Application of reverse phase ion-pair partition chromatography to drugs of forensic interest.", "content": "A method is described for determining a wide range of abused drugs by using 1 column, a single isocratic system, and a fixed wavelength (254 nm) ultraviolet detector. Paired-ion chromatography is performed on a reverse phase muBondapak C18 column. Acidic, basic, and neutral drugs, including their corresponding salts, can be determined without prior cleanup. A counter ion, 1-heptane sulfonate, is dissolved in the aqueous organic mobile phase to give a final pH of approximately 3.5. This technique is applicable to ergot alkaloids, phenylethylamines, opium alkaloids, local anesthetics, barbiturates, and other drugs of forensic interest. Five major opium alkaloids in gum opium, namely, morphine, codeine, thebaine, narcotine, and papaverine, can be separated in approximately 20 min.", "contents": "Application of reverse phase ion-pair partition chromatography to drugs of forensic interest. A method is described for determining a wide range of abused drugs by using 1 column, a single isocratic system, and a fixed wavelength (254 nm) ultraviolet detector. Paired-ion chromatography is performed on a reverse phase muBondapak C18 column. Acidic, basic, and neutral drugs, including their corresponding salts, can be determined without prior cleanup. A counter ion, 1-heptane sulfonate, is dissolved in the aqueous organic mobile phase to give a final pH of approximately 3.5. This technique is applicable to ergot alkaloids, phenylethylamines, opium alkaloids, local anesthetics, barbiturates, and other drugs of forensic interest. Five major opium alkaloids in gum opium, namely, morphine, codeine, thebaine, narcotine, and papaverine, can be separated in approximately 20 min."}
{"id": "PMID:19416", "title": "Comparison of two dioxygenases from Pseudomonas putida.", "content": "Catechol 2,3-dioxygenase and homoprotocatechuate 2,3-dioxygenase were purified from the same strain of Pseudomonas putida. Molecular weights and subunit sizes were similar, but amino acid compositions showed some marked differences.", "contents": "Comparison of two dioxygenases from Pseudomonas putida. Catechol 2,3-dioxygenase and homoprotocatechuate 2,3-dioxygenase were purified from the same strain of Pseudomonas putida. Molecular weights and subunit sizes were similar, but amino acid compositions showed some marked differences."}
{"id": "PMID:19417", "title": "Myxospore coat synthesis in Myxococcus xanthus: enzymes associated with uridine 5'-diphosphate-N-acetylgalactosamine formation during myxospore development.", "content": "Activities of the enzymes glutamine synthetase (EC 6.3.1.2.), glucosamine 6-phosphate acetyltransferase (EC 2.3.1.4.), uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase (EC 2.7.23.), UDP-N-acetylglucosamine 4-epimerase (EC 5.1.3.7.), fructose 1,6-diphosphate phosphatase (EC 3.13.11.), L-glutamine-fructose 6-phosphate transamidase (EC 5.3.1.19.), alkaline phosphatase (EC 3.1.3.1.), and malic dehydrogenase (EC 1.1.1.37) were assayed in partially purified extracts prepared at different stages of myxospore formation and germination in liquid cultures of Myxococcus xanthus. The specific activities of the first six of these enzymes increased 4.5- to 7.5-fold after 2 h of induction with 0.5 M glycerol or 0.2 M dimethyl sulfoxide. The increase in specific activities of these six enzymes was not observed in a mutant unable to be induced with glycerol. During the first 2 to 4 h of induction and during the first hour of germination, the level of these enzymes decreased to the level characteristic of vegetative cells. It is suggested that the six enzymes are responsible for the increased conversion of fructose 1,6-diphosphate to UDP-N-acetylgalactosamine, the major precursor of the myxospore coat.", "contents": "Myxospore coat synthesis in Myxococcus xanthus: enzymes associated with uridine 5'-diphosphate-N-acetylgalactosamine formation during myxospore development. Activities of the enzymes glutamine synthetase (EC 6.3.1.2.), glucosamine 6-phosphate acetyltransferase (EC 2.3.1.4.), uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase (EC 2.7.23.), UDP-N-acetylglucosamine 4-epimerase (EC 5.1.3.7.), fructose 1,6-diphosphate phosphatase (EC 3.13.11.), L-glutamine-fructose 6-phosphate transamidase (EC 5.3.1.19.), alkaline phosphatase (EC 3.1.3.1.), and malic dehydrogenase (EC 1.1.1.37) were assayed in partially purified extracts prepared at different stages of myxospore formation and germination in liquid cultures of Myxococcus xanthus. The specific activities of the first six of these enzymes increased 4.5- to 7.5-fold after 2 h of induction with 0.5 M glycerol or 0.2 M dimethyl sulfoxide. The increase in specific activities of these six enzymes was not observed in a mutant unable to be induced with glycerol. During the first 2 to 4 h of induction and during the first hour of germination, the level of these enzymes decreased to the level characteristic of vegetative cells. It is suggested that the six enzymes are responsible for the increased conversion of fructose 1,6-diphosphate to UDP-N-acetylgalactosamine, the major precursor of the myxospore coat."}
{"id": "PMID:19418", "title": "Induction of the acetamidase of Aspergillus nidulans by acetate metabolism.", "content": "Growth tests and enzyme determinations strongly suggest that the acetamidase of Aspergillus nidulans is induced by a product of acetate metabolism rather than the substrate, acetamide. The cis-dominant mutation, amdI9, which is closely linked to amdS, the structural gene for the acetamidase, results in greatly increased sensitivity to induction by acetate metabolism. Propionate, L-threonine, and ethanol also result in acetamidase induction. Mutations in the facA, facB, and facC genes, which lead to low levels of acetyl-coenzyme A synthase, are epistatic to the amdI9 mutation for strong growth on acetamide medium and abolish acetamide and propionamide induction of the acetamidase and isocitrate lyase enzymes. Acetate, L-threonine, and ethanol, however, can induce these enzymes in strains containing facA and facC lesions but not in strains containing a facB lesion. The evidence suggests that acetamidase and isocitrate lyase may be induced by a similar mechanism.", "contents": "Induction of the acetamidase of Aspergillus nidulans by acetate metabolism. Growth tests and enzyme determinations strongly suggest that the acetamidase of Aspergillus nidulans is induced by a product of acetate metabolism rather than the substrate, acetamide. The cis-dominant mutation, amdI9, which is closely linked to amdS, the structural gene for the acetamidase, results in greatly increased sensitivity to induction by acetate metabolism. Propionate, L-threonine, and ethanol also result in acetamidase induction. Mutations in the facA, facB, and facC genes, which lead to low levels of acetyl-coenzyme A synthase, are epistatic to the amdI9 mutation for strong growth on acetamide medium and abolish acetamide and propionamide induction of the acetamidase and isocitrate lyase enzymes. Acetate, L-threonine, and ethanol, however, can induce these enzymes in strains containing facA and facC lesions but not in strains containing a facB lesion. The evidence suggests that acetamidase and isocitrate lyase may be induced by a similar mechanism."}
{"id": "PMID:19419", "title": "Sodium ion-stimulated alpha-[1-14C]aminoisobutyric acid uptake in alkalophilic Bacillus species.", "content": "Alkalophilic Bacillus no. 8-1 grows well in alkaline media containing 2.5 to 5% NaCl. The uptake of alpha-aminoisobutyric acid (AIB) into the cells is stimulated by the addition of NaCl (Na+) up to a concentration of 0.2 M, but other monovalent cations such as K+, Li+, or NH4+ cannot substitute for Na+. The kinetic studies reveal that, when the Na+ concentration increases from 0.02 to 0.2 M in alkaline medium, the Km for transport decreases, whereas Vmax remains almost constant. Competition studies indicate that glycine, L-alanine, L-serine, and AIB share common carriers for the transport of the compounds into cells. Other alkalophilic bacteria are also found to require Na+ for the uptake of AIB into the cells.", "contents": "Sodium ion-stimulated alpha-[1-14C]aminoisobutyric acid uptake in alkalophilic Bacillus species. Alkalophilic Bacillus no. 8-1 grows well in alkaline media containing 2.5 to 5% NaCl. The uptake of alpha-aminoisobutyric acid (AIB) into the cells is stimulated by the addition of NaCl (Na+) up to a concentration of 0.2 M, but other monovalent cations such as K+, Li+, or NH4+ cannot substitute for Na+. The kinetic studies reveal that, when the Na+ concentration increases from 0.02 to 0.2 M in alkaline medium, the Km for transport decreases, whereas Vmax remains almost constant. Competition studies indicate that glycine, L-alanine, L-serine, and AIB share common carriers for the transport of the compounds into cells. Other alkalophilic bacteria are also found to require Na+ for the uptake of AIB into the cells."}
{"id": "PMID:19420", "title": "Metabolism of 6-aminonicotinic acid in Escherichia coli.", "content": "A late-log-phase culture of an Escherichia coli nadB pncA double mutant took up 6-[7-14C]aminonicotinic acid and excreted 6-[14C]aminonicotinamide. This mutant also accumulated intracellularly several radioactive compounds which have been tentatively identified as 6-amino analogs of compounds in the pyridine nucleotide cycle. It is concluded that 6-aminonicotinamide and 6-aminonicotinic acid probably exert at least a portion of their bacteriostatic effects by being metabolized, by the enzymes of the pyridine nucleotide cycle, to 6-aminonicotinamide adenine dinucleotide and 6-aminonicotinamide adenine dinucleotide phosphate. These compounds are not electron acceptors and are known inhibitors of some pyridine nucleotide-linked dehydrogenases.", "contents": "Metabolism of 6-aminonicotinic acid in Escherichia coli. A late-log-phase culture of an Escherichia coli nadB pncA double mutant took up 6-[7-14C]aminonicotinic acid and excreted 6-[14C]aminonicotinamide. This mutant also accumulated intracellularly several radioactive compounds which have been tentatively identified as 6-amino analogs of compounds in the pyridine nucleotide cycle. It is concluded that 6-aminonicotinamide and 6-aminonicotinic acid probably exert at least a portion of their bacteriostatic effects by being metabolized, by the enzymes of the pyridine nucleotide cycle, to 6-aminonicotinamide adenine dinucleotide and 6-aminonicotinamide adenine dinucleotide phosphate. These compounds are not electron acceptors and are known inhibitors of some pyridine nucleotide-linked dehydrogenases."}
{"id": "PMID:19421", "title": "Allantoin transport in Saccharomyces cerevisiae.", "content": "Allantoin uptake in both growing and resting cultures of Saccharomyces cerevisiae occurs by a low-Km (ca. 15 micrometer) transport system that uses energy that is likely generated in the cytoplasm. This conclusion was based on the observation that transport did not occur in the absence of glucose or the presence of dinitrophenol, carbonyl cyanide-m-chloro-phenyl hydrazine, fluoride, or arsenate ions. Normal uptake was observed, however, in the presence of cyanide. The rate of accumulation was maximal at pH 5.2. In contrast to the urea transport system, allantoin uptake appeared to be unidirectional. Preloaded, radioactive allantoin was not lost from cells suspended in allantoin-free buffer and did not exchange with exogenously added, nonradioactive allantoin. Treatment of preloaded cells with nystatin, however, released the accumulated radioactivity. Allantoin accumulated within cells was isolated and shown to be chemically unaltered.", "contents": "Allantoin transport in Saccharomyces cerevisiae. Allantoin uptake in both growing and resting cultures of Saccharomyces cerevisiae occurs by a low-Km (ca. 15 micrometer) transport system that uses energy that is likely generated in the cytoplasm. This conclusion was based on the observation that transport did not occur in the absence of glucose or the presence of dinitrophenol, carbonyl cyanide-m-chloro-phenyl hydrazine, fluoride, or arsenate ions. Normal uptake was observed, however, in the presence of cyanide. The rate of accumulation was maximal at pH 5.2. In contrast to the urea transport system, allantoin uptake appeared to be unidirectional. Preloaded, radioactive allantoin was not lost from cells suspended in allantoin-free buffer and did not exchange with exogenously added, nonradioactive allantoin. Treatment of preloaded cells with nystatin, however, released the accumulated radioactivity. Allantoin accumulated within cells was isolated and shown to be chemically unaltered."}
{"id": "PMID:19422", "title": "Cyclic adenosine 3',5'-monophosphate regulation of membrane energetics in Escherichia coli.", "content": "Mutants of Escherichia coli K-12 lacking functional adenylate cyclase (cya) or the cyclic adenosine 3',5'-monophosphate (cAMP) receptor protein (crp) were compared with their wild type to evaluate the role played by the cAMP-cAMP receptor protein complex in regulating this organism's membrane-associated bioenergetic functions. Both mutants were found to be equally defective in carrying out various electron transport activities. In particular, their capacity for synthesizing a functional oxygen-linked transhydrogenase system was totally repressed, and their content of flavin adenine dinucleotide was reduced by approximately 85%. In addition, it was found that the mutant strains had a decreased ability to generate a protonmotive force and to use this chemiosmotic force to generate adenosine 5'-triphosphate. All these membrane-associated dysfunctions were completely restored to the wild-type state when the cya cells were grown in the presence of exogenous cAMP. As would be expected if these controls were operating at the transcriptional level, the crp cells retained the mutant character even when grown in the presence of this cyclic nucleotide.", "contents": "Cyclic adenosine 3',5'-monophosphate regulation of membrane energetics in Escherichia coli. Mutants of Escherichia coli K-12 lacking functional adenylate cyclase (cya) or the cyclic adenosine 3',5'-monophosphate (cAMP) receptor protein (crp) were compared with their wild type to evaluate the role played by the cAMP-cAMP receptor protein complex in regulating this organism's membrane-associated bioenergetic functions. Both mutants were found to be equally defective in carrying out various electron transport activities. In particular, their capacity for synthesizing a functional oxygen-linked transhydrogenase system was totally repressed, and their content of flavin adenine dinucleotide was reduced by approximately 85%. In addition, it was found that the mutant strains had a decreased ability to generate a protonmotive force and to use this chemiosmotic force to generate adenosine 5'-triphosphate. All these membrane-associated dysfunctions were completely restored to the wild-type state when the cya cells were grown in the presence of exogenous cAMP. As would be expected if these controls were operating at the transcriptional level, the crp cells retained the mutant character even when grown in the presence of this cyclic nucleotide."}
{"id": "PMID:19423", "title": "Regulation of the Neurospora crassa assimilatory nitrate reductase.", "content": "Reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductase from Neurospora crassa was purified and found to be stimulated by certain amino acids, citrate, and ethylenediaminetetraacetic acid (EDTA). Stimulation by citrate and the amino acids was dependent upon the prior removal of EDTA from the enzyme preparations, since low quantities of EDTA resulted in maximal stimulation. Removal of EDTA from enzyme preparations by dialysis against Chelex-containing buffer resulted in a loss of nitrate reductase activity. Addition of alanine, arginine, glycine, glutamine, glutamate, histidine, tryptophan, and citrate restored and stimulated nitrate reductase activity from 29- to 46-fold. The amino acids tested altered the Km of NADPH-nitrate reductase for NADPH but did not significantly change that for nitrate. The Km of nitrate reductase for NADPH increased with increasing concentrations of histidine but decreased with increasing concentrations of glutamine. Amino acid modulation of NADPH-nitrate reductase activity is discussed in relation to the conservation of energy (NADPH) by Neurospora when nitrate is the nitrogen source.", "contents": "Regulation of the Neurospora crassa assimilatory nitrate reductase. Reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductase from Neurospora crassa was purified and found to be stimulated by certain amino acids, citrate, and ethylenediaminetetraacetic acid (EDTA). Stimulation by citrate and the amino acids was dependent upon the prior removal of EDTA from the enzyme preparations, since low quantities of EDTA resulted in maximal stimulation. Removal of EDTA from enzyme preparations by dialysis against Chelex-containing buffer resulted in a loss of nitrate reductase activity. Addition of alanine, arginine, glycine, glutamine, glutamate, histidine, tryptophan, and citrate restored and stimulated nitrate reductase activity from 29- to 46-fold. The amino acids tested altered the Km of NADPH-nitrate reductase for NADPH but did not significantly change that for nitrate. The Km of nitrate reductase for NADPH increased with increasing concentrations of histidine but decreased with increasing concentrations of glutamine. Amino acid modulation of NADPH-nitrate reductase activity is discussed in relation to the conservation of energy (NADPH) by Neurospora when nitrate is the nitrogen source."}
{"id": "PMID:19424", "title": "Alteration of the Bacillus subtilis glutamine synthetase results in overproduction of the enzyme.", "content": "A mutational leading to glutamine auxotrophy was located near a 5-fluorouracil resistance marker in the citB-thyA region of the Bacillus subtilis chromosome. This mutation resulted in a glutamine synthetase with altered kinetic and feedback properties. The specific activity of manganese-stimulated glutamine synthetase activity in crude extracts was 18-fold higher, and the magnesium-stimulated activity was about 30% that of the wild type. Quantitation of the enzyme by precipitation with antibody prepared against pure enzyme confirmed the presence of high enzyme levels in the mutant. This mutation is very closely linked (recombination index of 0.03) to another glutamine auxotroph containing enzyme with altered electrophoretic and heat sensitivity properties. Mutations in the structural gene for glutamine synthetase may result not only in altered catalytic and regulatory properties but also in altered production of the enzyme.", "contents": "Alteration of the Bacillus subtilis glutamine synthetase results in overproduction of the enzyme. A mutational leading to glutamine auxotrophy was located near a 5-fluorouracil resistance marker in the citB-thyA region of the Bacillus subtilis chromosome. This mutation resulted in a glutamine synthetase with altered kinetic and feedback properties. The specific activity of manganese-stimulated glutamine synthetase activity in crude extracts was 18-fold higher, and the magnesium-stimulated activity was about 30% that of the wild type. Quantitation of the enzyme by precipitation with antibody prepared against pure enzyme confirmed the presence of high enzyme levels in the mutant. This mutation is very closely linked (recombination index of 0.03) to another glutamine auxotroph containing enzyme with altered electrophoretic and heat sensitivity properties. Mutations in the structural gene for glutamine synthetase may result not only in altered catalytic and regulatory properties but also in altered production of the enzyme."}
{"id": "PMID:19425", "title": "Partial purification and characterization of L-lactate dehydrogenase isozymes from sweet potato roots.", "content": "Lactate dehydrogenase [L-lactate: NAD oxidoreductase, EC 1.1.1.27] was isolated from sweet potato root tissues. Two species of the enzyme (isozymes I and II) were separated by DE-52 cellulose column chromatography from healthy, cut, and black-rot diseased tissues. Isozymes I and II were purified from healthy and diseased tissues, respectively. Reduction of pyruvate by NADH with either isozyme I or II was inhibited by pyruvate at high concentrations, by NAD+ and by several mononucleotides. Isozyme I was inhibited by a lower concentration of adenine nucleotide than isozyme II, and Km for pyruvate was increased markedly at acidic pH in the case of isozyme I, but only slightly in the case of isozyme II. The molecular weights of both isozymes were determined to be 150,000 and they were found to be charge isomers by polyacrylamide gel electrophoresis. The enzyme activity increased in response to infection by black-rot fungus but decreased in response to cutting.", "contents": "Partial purification and characterization of L-lactate dehydrogenase isozymes from sweet potato roots. Lactate dehydrogenase [L-lactate: NAD oxidoreductase, EC 1.1.1.27] was isolated from sweet potato root tissues. Two species of the enzyme (isozymes I and II) were separated by DE-52 cellulose column chromatography from healthy, cut, and black-rot diseased tissues. Isozymes I and II were purified from healthy and diseased tissues, respectively. Reduction of pyruvate by NADH with either isozyme I or II was inhibited by pyruvate at high concentrations, by NAD+ and by several mononucleotides. Isozyme I was inhibited by a lower concentration of adenine nucleotide than isozyme II, and Km for pyruvate was increased markedly at acidic pH in the case of isozyme I, but only slightly in the case of isozyme II. The molecular weights of both isozymes were determined to be 150,000 and they were found to be charge isomers by polyacrylamide gel electrophoresis. The enzyme activity increased in response to infection by black-rot fungus but decreased in response to cutting."}
{"id": "PMID:19426", "title": "Studies on sterol-ester hydrolase from Fusarium oxysporum. I. Partial purification and properties.", "content": "1. A search for a long chain fatty acyl sterol-ester hydrolase in microorganisms led to the isolation from soil of five strains belonging to Fusarium sp. which produced strong activity in the culture medium. 2. The cholesterol esterase from Fusarium oxysporum IGH-2 was purified about 270-fold by means of CaCl2 precipitation and Sephadex G-75 column chromatography. 3. The cholesterol esterase was activated by adekatol and Triton X-100. It was inhibited by lecithin and lysolecithin, and completely inactivated by heat treatment (60 degrees C for 30 min, at pH 7.0). 4. The optimum pH of the enzyme was found to be around 7.0. 5. Among various cholesterol esters tested, cholesterol linoleate was the most suitable substrate. 6. Cholesterol esters in serum were also hydrolyzed by this enzyme.", "contents": "Studies on sterol-ester hydrolase from Fusarium oxysporum. I. Partial purification and properties. 1. A search for a long chain fatty acyl sterol-ester hydrolase in microorganisms led to the isolation from soil of five strains belonging to Fusarium sp. which produced strong activity in the culture medium. 2. The cholesterol esterase from Fusarium oxysporum IGH-2 was purified about 270-fold by means of CaCl2 precipitation and Sephadex G-75 column chromatography. 3. The cholesterol esterase was activated by adekatol and Triton X-100. It was inhibited by lecithin and lysolecithin, and completely inactivated by heat treatment (60 degrees C for 30 min, at pH 7.0). 4. The optimum pH of the enzyme was found to be around 7.0. 5. Among various cholesterol esters tested, cholesterol linoleate was the most suitable substrate. 6. Cholesterol esters in serum were also hydrolyzed by this enzyme."}
{"id": "PMID:19427", "title": "Isolation and partial characterization of the serum low density lipoprotein from bullfrog, Rana catesbeiana.", "content": "The chemical and physical properties of bullfrog serum low density lipoprotein (LDL) were investigated. On a weight percentage basis, LDL contained cholesterol ester, 30.3%; cholesterol, 5.6%; triglyceride, 12.5%; phospholipids, 23.3%; and protein, 22.4%. The fatty acid compositions of triglycerides and major phospholipids from the bullfrog serum LDL were quite similar to those of human serum LDL. However, the fatty acid composition of the chlesterol ester from the bullfrog serum LDL was quite different from that of the human serum LDL. The average particle weight, determined by gel filtration, was 2 X 10(6) daltons. This value is very close to that of human LDL. In the fluorescence emission spectrum of bullfrog serum LDL, the emission maximum was 324 nm. The amino acid composition of the apo-LDL resembled that of human apo-LDL.", "contents": "Isolation and partial characterization of the serum low density lipoprotein from bullfrog, Rana catesbeiana. The chemical and physical properties of bullfrog serum low density lipoprotein (LDL) were investigated. On a weight percentage basis, LDL contained cholesterol ester, 30.3%; cholesterol, 5.6%; triglyceride, 12.5%; phospholipids, 23.3%; and protein, 22.4%. The fatty acid compositions of triglycerides and major phospholipids from the bullfrog serum LDL were quite similar to those of human serum LDL. However, the fatty acid composition of the chlesterol ester from the bullfrog serum LDL was quite different from that of the human serum LDL. The average particle weight, determined by gel filtration, was 2 X 10(6) daltons. This value is very close to that of human LDL. In the fluorescence emission spectrum of bullfrog serum LDL, the emission maximum was 324 nm. The amino acid composition of the apo-LDL resembled that of human apo-LDL."}
{"id": "PMID:19428", "title": "Separation of newly-synthesized RNA by organomercurial agarose affinity chromatography.", "content": "Mouse myeloma cells, MOPC-31C, were incubated in the presence of 2-thiouridine and newly-synthesized RNA which appeared to contain 2-thioUMP as a constituent was separated from preexisting RNA by affinity chromatography using organomercurial agarose as a support. Both pH and salt concentration greatly affected the specific adsorption of the newly-synthesized RNA on the column. Under optimal conditions the rate of adsorption of the newly-synthesized RNA on the column was proportional to the logarithmic concentration of 2-thiouridine in the culture medium. Furthermore, at a given concentration of 2-thiouridine in the medium, a shorter incubation period caused a reduction of the rate of RNA adsorption on the column. The molecular size distributions of both total RNA and the adsorbed fraction, synthesized during 30 min in the presence of 2-thiouridine, were similar to that of RNA synthesized in the absence of the drug.", "contents": "Separation of newly-synthesized RNA by organomercurial agarose affinity chromatography. Mouse myeloma cells, MOPC-31C, were incubated in the presence of 2-thiouridine and newly-synthesized RNA which appeared to contain 2-thioUMP as a constituent was separated from preexisting RNA by affinity chromatography using organomercurial agarose as a support. Both pH and salt concentration greatly affected the specific adsorption of the newly-synthesized RNA on the column. Under optimal conditions the rate of adsorption of the newly-synthesized RNA on the column was proportional to the logarithmic concentration of 2-thiouridine in the culture medium. Furthermore, at a given concentration of 2-thiouridine in the medium, a shorter incubation period caused a reduction of the rate of RNA adsorption on the column. The molecular size distributions of both total RNA and the adsorbed fraction, synthesized during 30 min in the presence of 2-thiouridine, were similar to that of RNA synthesized in the absence of the drug."}
{"id": "PMID:19429", "title": "Interaction of Asp. melleus Semi-alkaline protease with benzeneboronic acid.", "content": "Benzeneboronic acid (BBA), a possible transition-state analog for serine proteases, was found to inhibit Asp. melleus semi-alkaline protease [EC 3.4.21.15]. The pH dependence of inhibitor constants was studied by the pH-stat method using N-acetyl-L-tyrosine ethyl ester as a substrate at 25 degrees C. From the pH dependence of the association constant (reciprocal inhibitor constant), a pK value of 6.6, which may be attributable to the catalytic histidine residue of the enzyme, was estimated. The BBA-enzyme interaction was studied kinetically by the temperature-jump method. Apparent association and dissociation rate constants were determined at pH 6.5.", "contents": "Interaction of Asp. melleus Semi-alkaline protease with benzeneboronic acid. Benzeneboronic acid (BBA), a possible transition-state analog for serine proteases, was found to inhibit Asp. melleus semi-alkaline protease [EC 3.4.21.15]. The pH dependence of inhibitor constants was studied by the pH-stat method using N-acetyl-L-tyrosine ethyl ester as a substrate at 25 degrees C. From the pH dependence of the association constant (reciprocal inhibitor constant), a pK value of 6.6, which may be attributable to the catalytic histidine residue of the enzyme, was estimated. The BBA-enzyme interaction was studied kinetically by the temperature-jump method. Apparent association and dissociation rate constants were determined at pH 6.5."}
{"id": "PMID:19430", "title": "Thermal denaturation of cytochromes c of horse cow, and Candida krusei in aqueous guanidine hydrochloride.", "content": "Thermal denaturation of cytochromes c of horse, cow, and Candida krusei in aqueous guanidine hydrochloride in the neutral pH region was studied by means of absorption and optical rotation measurements. The values of standard free energy change upon denaturation were estimated over the temperature range from 3 to 51 degrees C. Large differences in the heat capacity of the native and denatured states amounting to several kcal/mol-deg were obtained for all three kinds of cytochromes c. These lead to a change in the sign of both the enthalpy and entropy change of denaturation, with maximum stability of the native state at 12 degrees C for horse and bovine cytochromes c and at 9 degrees C for Candida krusei.", "contents": "Thermal denaturation of cytochromes c of horse cow, and Candida krusei in aqueous guanidine hydrochloride. Thermal denaturation of cytochromes c of horse, cow, and Candida krusei in aqueous guanidine hydrochloride in the neutral pH region was studied by means of absorption and optical rotation measurements. The values of standard free energy change upon denaturation were estimated over the temperature range from 3 to 51 degrees C. Large differences in the heat capacity of the native and denatured states amounting to several kcal/mol-deg were obtained for all three kinds of cytochromes c. These lead to a change in the sign of both the enthalpy and entropy change of denaturation, with maximum stability of the native state at 12 degrees C for horse and bovine cytochromes c and at 9 degrees C for Candida krusei."}
{"id": "PMID:19431", "title": "Dihydrodipicolinate reductases from Bacillus cereus and Bacillus megaterium.", "content": "Dyhydrodipicolinate reductases were purified 100-fold from crude extracts of B. cereus and B. megaterium and their properties were compared with those of the reductase from B. subtilis. The molecular weights of the reductases of B. cereus and B. megaterium were fount to be 155,000 and 150,000, respectively. These reductases were shown to be free of flavin, unlike the B. subtilis enzyme, which contains flavin. Both NADPH and NADH acted as coenzymes for these two reductases. NADPH being three or four times more effective than NADH. The Km values for NADPH and dihydrodipicolinate were 8 micrometer and 62 micrometer, respectively, with B. cereus reductase, and 13 micrometer and 59 micrometer with B. megaterium reductase. The pH optima of the enzymes from B. cereus and B. megaterium were pH 7.4 and 7.2, respectively. The reductases were inhibited by dipicolinate noncompetitively with respect to dihydrodipicolinate and the Ki values were 85 micrometer and 140 micrometer, respectively. Lysine and diaminopimelate were not inhibitory. The properties of the reductases from B. cereus and B. megaterium were similar, but they differed considerably from those of the B. subtilis enzyme. However, all three Bacillus reductases were markedly inhibited by dipicolinate, unlike the enzyme from E. coli.", "contents": "Dihydrodipicolinate reductases from Bacillus cereus and Bacillus megaterium. Dyhydrodipicolinate reductases were purified 100-fold from crude extracts of B. cereus and B. megaterium and their properties were compared with those of the reductase from B. subtilis. The molecular weights of the reductases of B. cereus and B. megaterium were fount to be 155,000 and 150,000, respectively. These reductases were shown to be free of flavin, unlike the B. subtilis enzyme, which contains flavin. Both NADPH and NADH acted as coenzymes for these two reductases. NADPH being three or four times more effective than NADH. The Km values for NADPH and dihydrodipicolinate were 8 micrometer and 62 micrometer, respectively, with B. cereus reductase, and 13 micrometer and 59 micrometer with B. megaterium reductase. The pH optima of the enzymes from B. cereus and B. megaterium were pH 7.4 and 7.2, respectively. The reductases were inhibited by dipicolinate noncompetitively with respect to dihydrodipicolinate and the Ki values were 85 micrometer and 140 micrometer, respectively. Lysine and diaminopimelate were not inhibitory. The properties of the reductases from B. cereus and B. megaterium were similar, but they differed considerably from those of the B. subtilis enzyme. However, all three Bacillus reductases were markedly inhibited by dipicolinate, unlike the enzyme from E. coli."}
{"id": "PMID:19432", "title": "Two omega-amino acid transaminases from Bacillus cereus.", "content": "Bacillus cereus strain K-22 produced two distinct omega-amino acid transaminases, one catalyzing the transamination between beta-alanine and pyruvic acid and the other that between gamma-aminobutyric acid and alpha-ketoglutaric aic. The two enzymes were partially purified and separated from each other by various chromatographies. beta-Alanine:pyruvic acid transaminase and gamma-aminobutyric acid:alpha-ketoglutaric acid transaminase were induced by the addition of beta-alanine and gamma-aminobutyric acid, respectively, to the growth medium. beta-Alanine transaminase showed an optimum pH of 10.0 and optimum temperature of 35 degrees C, and its Km values for beta-alanine and pyruvic acid were both 1.1 mM. gamma-Aminobutyric acid, epsilon-aminocaproic acid, 2-aminoethylphosphonic acid, and propylamine showed about 30-40% of the activity of beta-alanine as amino donors, and oxalacetic acid was as good an amino acceptor as pyruvic acid. The optimum pH and temperature of gamma-aminobutyric acid transaminase were 9.0 and 50 degrees C, respectively, and its Km value for gamma-aminobutyric acid was 2.8 mM, while that for alpha-ketoglutaric acid was 2.3 mM. gamma-Aminobutyric acid and delta-aminovaleric acid were good amino donors but other omega-amino acids were virtually inactive with gamma-aminobutyric acid transaminase; alpha-ketoglutaric acid, and to a lesser extent glyoxylic acid, were active amino acceptors. Sulfhydryl reagents specifically activated gamma-aminobutyric acid transaminase.", "contents": "Two omega-amino acid transaminases from Bacillus cereus. Bacillus cereus strain K-22 produced two distinct omega-amino acid transaminases, one catalyzing the transamination between beta-alanine and pyruvic acid and the other that between gamma-aminobutyric acid and alpha-ketoglutaric aic. The two enzymes were partially purified and separated from each other by various chromatographies. beta-Alanine:pyruvic acid transaminase and gamma-aminobutyric acid:alpha-ketoglutaric acid transaminase were induced by the addition of beta-alanine and gamma-aminobutyric acid, respectively, to the growth medium. beta-Alanine transaminase showed an optimum pH of 10.0 and optimum temperature of 35 degrees C, and its Km values for beta-alanine and pyruvic acid were both 1.1 mM. gamma-Aminobutyric acid, epsilon-aminocaproic acid, 2-aminoethylphosphonic acid, and propylamine showed about 30-40% of the activity of beta-alanine as amino donors, and oxalacetic acid was as good an amino acceptor as pyruvic acid. The optimum pH and temperature of gamma-aminobutyric acid transaminase were 9.0 and 50 degrees C, respectively, and its Km value for gamma-aminobutyric acid was 2.8 mM, while that for alpha-ketoglutaric acid was 2.3 mM. gamma-Aminobutyric acid and delta-aminovaleric acid were good amino donors but other omega-amino acids were virtually inactive with gamma-aminobutyric acid transaminase; alpha-ketoglutaric acid, and to a lesser extent glyoxylic acid, were active amino acceptors. Sulfhydryl reagents specifically activated gamma-aminobutyric acid transaminase."}
{"id": "PMID:19433", "title": "Affinity labeling of adenine nucleotide-related enzymes with reactive adenine nucleotide analogs. II. Affinity labeling of phosphoglycerate kinase with a reactive AMP analog.", "content": "Affinity labeling of yeast and B. stearothermophilus phosphoglycerate kinases with a reactive AMP analog, N6-(p-bromoacetaminobenzyl)-AMP was examined. Complete loss of enzyme activity was observed when 1 mol of the reagent had reacted per mol of either enzyme. Results on the effect of pH and substrate addition on the inactivation, titration of SH groups before and after modification, and kinetic studies with AMP analogs suggest that the modification occurs at one amino group at or near the substrate binding site. General affinity labeling of kinases is discussed based on the results obtained.", "contents": "Affinity labeling of adenine nucleotide-related enzymes with reactive adenine nucleotide analogs. II. Affinity labeling of phosphoglycerate kinase with a reactive AMP analog. Affinity labeling of yeast and B. stearothermophilus phosphoglycerate kinases with a reactive AMP analog, N6-(p-bromoacetaminobenzyl)-AMP was examined. Complete loss of enzyme activity was observed when 1 mol of the reagent had reacted per mol of either enzyme. Results on the effect of pH and substrate addition on the inactivation, titration of SH groups before and after modification, and kinetic studies with AMP analogs suggest that the modification occurs at one amino group at or near the substrate binding site. General affinity labeling of kinases is discussed based on the results obtained."}
{"id": "PMID:19435", "title": "Effect of halide anions on the binding of FAD to D-amino acid oxidase and the tryptophanyl fluorescence of the apoenzyme.", "content": "The quenching of tryptophanyl fluorescence of native and denatured D-amino acid oxidase from hog kidney was measured. About 60% of the tryptophanyl fluorescence of the native apoenzyme was quenched by iodide at pH 8.3, and 25 degrees C. All of the tryptophanyl fluorescence of the apoenzyme in 6 M guanidine hydrochloride was quenched. The tryptophanyl fluorescence quenching of the holoenzyme by 1-methyl nicotinamide chloride was low in comparison with that of the apoenzyme. These results of the quenching experiments are discussed based on the intermolecular collision quenching mechanism. By measuring the fluorescence intensities of the tryptophanyl residues and FAD of the holoenzyme solution, and the fluorescence polarization of the holoenzyme solution containing halide anions such as iodide, bromide, chloride, or fluoride, we found that FAD dissociates from the holoenzyme in the presence of iodide, bromide, or chloride, and the ability to dissociate FAD from the holoenzyme decreases in order iodide, bromide, and chloride. However, fluoride seems to enhance the association reaction of FAD with the apoenzyme. These results were consistent with the visible absorption spectra and derivative spectra of free FAD and the holoenzyme in the presence and absence of halide anions.", "contents": "Effect of halide anions on the binding of FAD to D-amino acid oxidase and the tryptophanyl fluorescence of the apoenzyme. The quenching of tryptophanyl fluorescence of native and denatured D-amino acid oxidase from hog kidney was measured. About 60% of the tryptophanyl fluorescence of the native apoenzyme was quenched by iodide at pH 8.3, and 25 degrees C. All of the tryptophanyl fluorescence of the apoenzyme in 6 M guanidine hydrochloride was quenched. The tryptophanyl fluorescence quenching of the holoenzyme by 1-methyl nicotinamide chloride was low in comparison with that of the apoenzyme. These results of the quenching experiments are discussed based on the intermolecular collision quenching mechanism. By measuring the fluorescence intensities of the tryptophanyl residues and FAD of the holoenzyme solution, and the fluorescence polarization of the holoenzyme solution containing halide anions such as iodide, bromide, chloride, or fluoride, we found that FAD dissociates from the holoenzyme in the presence of iodide, bromide, or chloride, and the ability to dissociate FAD from the holoenzyme decreases in order iodide, bromide, and chloride. However, fluoride seems to enhance the association reaction of FAD with the apoenzyme. These results were consistent with the visible absorption spectra and derivative spectra of free FAD and the holoenzyme in the presence and absence of halide anions."}
{"id": "PMID:19437", "title": "Purification and some properties of rabbit stomach myosin.", "content": "Myosin from rabbit stomach was highly purified by ammonium sulfate fractionation in the presence of ATP and MgCl2, ultracentrifugation and Sepharose 4B chromatography. The myosin composed of one heavy and two light chains as determined by SDS-gel electrophoresis. The molecular weights of the light chains were the same as those of gizzard myosin, about 20,000 and 17,000, respectively. The pH-activity curve and the KCl concentration dependency of Ca-ATPase of the stomach myosin were similar to those of other smooth muscle myosins. The stomach myosin was more resistant to pepsin digestion than skeletal myosin. Other proteolytic enzymes, trypsin, chymotrypsin, papain, and nagarse, digested the myosin in the same way as skeletal myosin.", "contents": "Purification and some properties of rabbit stomach myosin. Myosin from rabbit stomach was highly purified by ammonium sulfate fractionation in the presence of ATP and MgCl2, ultracentrifugation and Sepharose 4B chromatography. The myosin composed of one heavy and two light chains as determined by SDS-gel electrophoresis. The molecular weights of the light chains were the same as those of gizzard myosin, about 20,000 and 17,000, respectively. The pH-activity curve and the KCl concentration dependency of Ca-ATPase of the stomach myosin were similar to those of other smooth muscle myosins. The stomach myosin was more resistant to pepsin digestion than skeletal myosin. Other proteolytic enzymes, trypsin, chymotrypsin, papain, and nagarse, digested the myosin in the same way as skeletal myosin."}
{"id": "PMID:19438", "title": "Accumulation of phosphoenolpyruvate in red cells incubated with the phosphate ester in an acidified isotonic sucrose medium.", "content": "Accumulation of exogenous phosphoenolpyruvate against the concentration gradient was observed when human red cells were incubated in an acidified isotonic sucrose medium. Fluoride  increased the apparent accumulation by inhibition of the intracellular metabolic interconversion of the phosphate compound. The accumulation appeared to be specific for phosphoenolpyruvate and the accumulation rate for 3-phosphoglycerate, which has a molecular size and pKa similar to those of phosphoenolpyruvate, was less than one-tenth of the rate of phosphoenolpyruvate. Red cells incubated in the acidified sucrose medium tended to adhere to each other when examined with a scanning electron microscope.", "contents": "Accumulation of phosphoenolpyruvate in red cells incubated with the phosphate ester in an acidified isotonic sucrose medium. Accumulation of exogenous phosphoenolpyruvate against the concentration gradient was observed when human red cells were incubated in an acidified isotonic sucrose medium. Fluoride  increased the apparent accumulation by inhibition of the intracellular metabolic interconversion of the phosphate compound. The accumulation appeared to be specific for phosphoenolpyruvate and the accumulation rate for 3-phosphoglycerate, which has a molecular size and pKa similar to those of phosphoenolpyruvate, was less than one-tenth of the rate of phosphoenolpyruvate. Red cells incubated in the acidified sucrose medium tended to adhere to each other when examined with a scanning electron microscope."}
{"id": "PMID:19439", "title": "A sensitive substrate for the clotting enzyme in horseshoe crab hemocytes.", "content": "An endotoxin-activated hemocyte lysate from horseshoe crab (Tachypleus and Limulus) was found to hydrolyze specifically BZ-Ile-Glu-Gly-Arg-p-nitroanilide, which was recently introduced as the substrate for assay of the blood coagulation factor, Factor Xa. Further, this amidase activity increased by increasing the concentration of bacterial endotoxin (Salmonella minnesota R595) added to the lysate. Thus, the measurement of the amidase activity in the hemocyte lysate can be very useful to detect and determine the endotoxin.", "contents": "A sensitive substrate for the clotting enzyme in horseshoe crab hemocytes. An endotoxin-activated hemocyte lysate from horseshoe crab (Tachypleus and Limulus) was found to hydrolyze specifically BZ-Ile-Glu-Gly-Arg-p-nitroanilide, which was recently introduced as the substrate for assay of the blood coagulation factor, Factor Xa. Further, this amidase activity increased by increasing the concentration of bacterial endotoxin (Salmonella minnesota R595) added to the lysate. Thus, the measurement of the amidase activity in the hemocyte lysate can be very useful to detect and determine the endotoxin."}
{"id": "PMID:19440", "title": "Biosynthesis of glycogen in Neurospora crassa. Existence of a glucoproteic intermediate in the initiation process.", "content": "A soluble enzyme preparation (20,000 X g supernatant fraction), prepared from the mycelia of wild-type Neurospora crassa, was capable of transferring [14C]glucose from UDP-[14C]glucose into both trichloroacetic acid (TCA)-soluble and TCA-insoluble macromolecule products in the absence of added primer. These reactions did not require either high concentrations of salts or any other chemical reagents. Two labeled products were formed; one was a glycogen-like polysaccharide and the other was a glycoprotein with glucosyl chains bound to protein through an acid-labile bond. After mild treatment of the glucoprotein with acid, the product liberated from the protein behaved as a mixture of malto-oligosaccharides and alpha-1,4-glucan with branches. The carbohydrate moiety of the glucoprotein seemed to be released upon prolonged incubation with the enzyme preparation. The glucan thus liberated from the glucoprotein may serve as a primer for the glycogen synthase. The results obtained are therefore suggestive of the existence of a glucoproteic intermediate in the initiation of glycogen biosynthesis.", "contents": "Biosynthesis of glycogen in Neurospora crassa. Existence of a glucoproteic intermediate in the initiation process. A soluble enzyme preparation (20,000 X g supernatant fraction), prepared from the mycelia of wild-type Neurospora crassa, was capable of transferring [14C]glucose from UDP-[14C]glucose into both trichloroacetic acid (TCA)-soluble and TCA-insoluble macromolecule products in the absence of added primer. These reactions did not require either high concentrations of salts or any other chemical reagents. Two labeled products were formed; one was a glycogen-like polysaccharide and the other was a glycoprotein with glucosyl chains bound to protein through an acid-labile bond. After mild treatment of the glucoprotein with acid, the product liberated from the protein behaved as a mixture of malto-oligosaccharides and alpha-1,4-glucan with branches. The carbohydrate moiety of the glucoprotein seemed to be released upon prolonged incubation with the enzyme preparation. The glucan thus liberated from the glucoprotein may serve as a primer for the glycogen synthase. The results obtained are therefore suggestive of the existence of a glucoproteic intermediate in the initiation of glycogen biosynthesis."}
{"id": "PMID:19441", "title": "Studies on adrenaline-induced lipolysis in artificial lipid micelles.", "content": "Lipid micelles were prepared by incubating a mixture of glycerides (triolein, diolein, and monoolein), and lecithin in Krebs-Ringer phosphate buffer at 37 degrees C for 30 min. It was found that adrenaline stimulated the release of free fatty acids in a lipolytic system consisting of the lipid micelles and adipose tissue lipase. Adrenaline did not increase the cyclic AMP content of the reaction mixture. Dibutyryl cyclic AMP, theophylline, and phospholipase C increased the rate of lipolysis in the system but cyclic AMP and phospholipase D did not.", "contents": "Studies on adrenaline-induced lipolysis in artificial lipid micelles. Lipid micelles were prepared by incubating a mixture of glycerides (triolein, diolein, and monoolein), and lecithin in Krebs-Ringer phosphate buffer at 37 degrees C for 30 min. It was found that adrenaline stimulated the release of free fatty acids in a lipolytic system consisting of the lipid micelles and adipose tissue lipase. Adrenaline did not increase the cyclic AMP content of the reaction mixture. Dibutyryl cyclic AMP, theophylline, and phospholipase C increased the rate of lipolysis in the system but cyclic AMP and phospholipase D did not."}
{"id": "PMID:19442", "title": "Purification of lipase from Chromobacterium viscosum by chromatography on palmitoyl cellulose.", "content": "Palmitoyl cellulose was used to adsorb the extracellular lipase [triacylglycerol acyl-hydrolase EC 3.1.1.3] of Chromobacterium viscosum from crude enzyme solution, and the adsorbed enzyme was eluted with a suitable detergent, such as Adekatol 45-S-8 or Triton X-100. The enzyme was then purified by chromatography on a palmitoylated gauze column with an overall recovery of 71% and an increase in the specific activity of 11-fold from the supernatant fluid of bacterial cultures. Further purification procedures included fractionation with acetone, and chromatography on Sephadex G-150 and G-75 columns. Two isoenzymes were obtained, each in a homogeneous state on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis: one had a molecular weight of 120,000 and pI of 3.7 and the other a molecular weight of 30,000 with a pI of 7.3.", "contents": "Purification of lipase from Chromobacterium viscosum by chromatography on palmitoyl cellulose. Palmitoyl cellulose was used to adsorb the extracellular lipase [triacylglycerol acyl-hydrolase EC 3.1.1.3] of Chromobacterium viscosum from crude enzyme solution, and the adsorbed enzyme was eluted with a suitable detergent, such as Adekatol 45-S-8 or Triton X-100. The enzyme was then purified by chromatography on a palmitoylated gauze column with an overall recovery of 71% and an increase in the specific activity of 11-fold from the supernatant fluid of bacterial cultures. Further purification procedures included fractionation with acetone, and chromatography on Sephadex G-150 and G-75 columns. Two isoenzymes were obtained, each in a homogeneous state on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis: one had a molecular weight of 120,000 and pI of 3.7 and the other a molecular weight of 30,000 with a pI of 7.3."}
{"id": "PMID:19443", "title": "A correlation between the secondary structure of DNA and the reactivity of adenine residues with chloroacetaldehyde.", "content": "The rate of reaction of chloroacetaldehyde (0.039 M) with the \"free\" adenine residue in deoxyadenosine-5'-phosphate (dAMP) at pH 6.5 has been found to be nearly equal to that at pH 4.5. Practically 100% of the adenine is converted to a fluorescent product (epsilon-adenine residue) on incubation for 60 h at 37 degrees C and pH 6.5. Of the adenine residues in \"single-stranded\" DNA, however, only 14% react with chloroacetaldehyde (0.039 M) under the same incubation conditions. The reaction rate of this 14% is nearly equal to that of dAMP, but the fluorescence of the product is appreciably quenched; the quantum yield is only 0.45 times that of the \"free\" adenine residue. In \"double-helical\" DNA, on the other hand, no adenine residue has been found to react with chloracetaldehyde. Possible application of these findings to structural studies of DNA is suggested.", "contents": "A correlation between the secondary structure of DNA and the reactivity of adenine residues with chloroacetaldehyde. The rate of reaction of chloroacetaldehyde (0.039 M) with the \"free\" adenine residue in deoxyadenosine-5'-phosphate (dAMP) at pH 6.5 has been found to be nearly equal to that at pH 4.5. Practically 100% of the adenine is converted to a fluorescent product (epsilon-adenine residue) on incubation for 60 h at 37 degrees C and pH 6.5. Of the adenine residues in \"single-stranded\" DNA, however, only 14% react with chloroacetaldehyde (0.039 M) under the same incubation conditions. The reaction rate of this 14% is nearly equal to that of dAMP, but the fluorescence of the product is appreciably quenched; the quantum yield is only 0.45 times that of the \"free\" adenine residue. In \"double-helical\" DNA, on the other hand, no adenine residue has been found to react with chloracetaldehyde. Possible application of these findings to structural studies of DNA is suggested."}
{"id": "PMID:19444", "title": "C-Terminal peptidyl-L-proline hydrolase activity of Aspergillus acid carboxypeptidase.", "content": "Aspergillus saitoi acid carboxypeptidase hydrolyzed C-terminal peptidyl-L-proline bonds and released the C-terminal proline from Z-Gly-Pro-Leu-Gly-Pro and Z-Gly-Pro at pH 3.3. Proline liberated by the enzymic reaction was measured by a sensitive colorimetric ninhydrin method in glacial acetic acid at 513 nm. A Km value of 1.0 mM and a kcat value of 0.09 s-1 for Z-Gly-Pro-Leu-Gly-Pro hydrolysis, and a Km value of 5.0 mM and a kcat value of 0.0045 s-1 for Z-Gly-Pro hydrolysis were calculated from Lineweaver-Burk plots.", "contents": "C-Terminal peptidyl-L-proline hydrolase activity of Aspergillus acid carboxypeptidase. Aspergillus saitoi acid carboxypeptidase hydrolyzed C-terminal peptidyl-L-proline bonds and released the C-terminal proline from Z-Gly-Pro-Leu-Gly-Pro and Z-Gly-Pro at pH 3.3. Proline liberated by the enzymic reaction was measured by a sensitive colorimetric ninhydrin method in glacial acetic acid at 513 nm. A Km value of 1.0 mM and a kcat value of 0.09 s-1 for Z-Gly-Pro-Leu-Gly-Pro hydrolysis, and a Km value of 5.0 mM and a kcat value of 0.0045 s-1 for Z-Gly-Pro hydrolysis were calculated from Lineweaver-Burk plots."}
{"id": "PMID:19447", "title": "Regulation of protein synthesis in hen's oviducts. II. Extracellular ovalbumin as an inhibitor of ovalbumin synthesis in the oviducts.", "content": "Washed, preincubated minced hen's oviducts, which contained low levels of extracellular and intracellular proteins, synthesized egg-white proteins actively. The addition of ovalbumin to the incubation medium resulted in inhibition of the synthesis of egg-white proteins by the washed, preincubated oviduct cells, while the addition of bovine serum albumin seemed to stimulate protein synthesis and hen's egg-white lysozyme had no effect. The inhibitory or stimulatory effect on protein synthesis was proportional to the amount of protein added to the medium. The inhibitory effect of added ovalbumin was shown not to be due to the incorporation of ovalbumin into the oviduct cells from the incubation medium. Egg-white proteins added to the medium also inhibited protein synthesis inside the cells and the extent of the inhibition appeared to correspond to the amount of ovalbumin present in egg-white.", "contents": "Regulation of protein synthesis in hen's oviducts. II. Extracellular ovalbumin as an inhibitor of ovalbumin synthesis in the oviducts. Washed, preincubated minced hen's oviducts, which contained low levels of extracellular and intracellular proteins, synthesized egg-white proteins actively. The addition of ovalbumin to the incubation medium resulted in inhibition of the synthesis of egg-white proteins by the washed, preincubated oviduct cells, while the addition of bovine serum albumin seemed to stimulate protein synthesis and hen's egg-white lysozyme had no effect. The inhibitory or stimulatory effect on protein synthesis was proportional to the amount of protein added to the medium. The inhibitory effect of added ovalbumin was shown not to be due to the incorporation of ovalbumin into the oviduct cells from the incubation medium. Egg-white proteins added to the medium also inhibited protein synthesis inside the cells and the extent of the inhibition appeared to correspond to the amount of ovalbumin present in egg-white."}
{"id": "PMID:19450", "title": "Interaction of thiolsubtilisin with Streptomyces subtilisin inhibitor, SSI.", "content": "Subtilisin BPN' was chemically converted to thiolsubtilisin and the interaction of this modified enzyme with Streptomyces subtilisin inhibitor (SSI) was examined. SSI competitively inhibited the esterolytic activity of thiolsubtilisin toward p-nitrophenyl acetate with a K1 value of 1.3 X 10(-5) M at pH 7.5 Spectrophotometric analysis of the interaction between SSI and the modified enzyme yielded a Kd value of 4 X 10(-5) M at pH 9.7. These values are about 10(5)-fold greater than the Kd value (less than 10(-9) M at pH 7.5) for the native enzyme. This indicates that the small change in the active site structure of subtilisin (Ser221 to Cys221) leads to a considerable decrease in the binding affinity (by about 6-7 kcal/mol) to SSI.", "contents": "Interaction of thiolsubtilisin with Streptomyces subtilisin inhibitor, SSI. Subtilisin BPN' was chemically converted to thiolsubtilisin and the interaction of this modified enzyme with Streptomyces subtilisin inhibitor (SSI) was examined. SSI competitively inhibited the esterolytic activity of thiolsubtilisin toward p-nitrophenyl acetate with a K1 value of 1.3 X 10(-5) M at pH 7.5 Spectrophotometric analysis of the interaction between SSI and the modified enzyme yielded a Kd value of 4 X 10(-5) M at pH 9.7. These values are about 10(5)-fold greater than the Kd value (less than 10(-9) M at pH 7.5) for the native enzyme. This indicates that the small change in the active site structure of subtilisin (Ser221 to Cys221) leads to a considerable decrease in the binding affinity (by about 6-7 kcal/mol) to SSI."}
{"id": "PMID:19451", "title": "Effects of adenosine triphosphate on N-ethylmaleimide-induced modification of 30S dynein from Tetrahymena cilia.", "content": "Ciliary 30S dynein of Tetrahymena was investigated with regard to modification of the ATPase activity with N-ethylmaleimide (NEM) in the presence of ATP. The elevation of enzyme activity due to the modification was largely repressed by addition of ATP at a concentration of 1 mM or more during preincubation of 20 h at 0 degrees C. The repression was highly specific for ATP, though ADP and AMPPNP showed slight repressive effects. After complete hydrolysis of ATP added to the preincubation mixture, however, elevation of 30S dynein ATPase activity occurred. It is suggested that the repression by ATP of NEM-induced elevation of 30S dynein ATPase activity is simply due to a protecting effect of ATP on certain SH group(s) (probably SH1-type group(s)) around the active center of 30S dynein. When 30S dynein was maximally activated by modification with NEM, ATP or ADP did not significantly promote the inactivation of the modified enzyme upon further treatment with NEM, indicating that 30S dynein lacks the characteristics of SH2-type groups. On the other hand, ATP also showed a protective effect against inhibition of native 30S dynein by high concentrations of NEM. High concentrations of ADP and AMPPNP were inhibitory to 30S dynein ATPase activity but inorganic phosphate did not inhibit 14S or 30S dynein ATPase activities at all.", "contents": "Effects of adenosine triphosphate on N-ethylmaleimide-induced modification of 30S dynein from Tetrahymena cilia. Ciliary 30S dynein of Tetrahymena was investigated with regard to modification of the ATPase activity with N-ethylmaleimide (NEM) in the presence of ATP. The elevation of enzyme activity due to the modification was largely repressed by addition of ATP at a concentration of 1 mM or more during preincubation of 20 h at 0 degrees C. The repression was highly specific for ATP, though ADP and AMPPNP showed slight repressive effects. After complete hydrolysis of ATP added to the preincubation mixture, however, elevation of 30S dynein ATPase activity occurred. It is suggested that the repression by ATP of NEM-induced elevation of 30S dynein ATPase activity is simply due to a protecting effect of ATP on certain SH group(s) (probably SH1-type group(s)) around the active center of 30S dynein. When 30S dynein was maximally activated by modification with NEM, ATP or ADP did not significantly promote the inactivation of the modified enzyme upon further treatment with NEM, indicating that 30S dynein lacks the characteristics of SH2-type groups. On the other hand, ATP also showed a protective effect against inhibition of native 30S dynein by high concentrations of NEM. High concentrations of ADP and AMPPNP were inhibitory to 30S dynein ATPase activity but inorganic phosphate did not inhibit 14S or 30S dynein ATPase activities at all."}
{"id": "PMID:19452", "title": "Collagenase of human skin basal cell epithelioma.", "content": "Collagenase of human basal cell epithelioma was purified by sequential ammonium sulfate precipitation, Sephadex gel filtration and affinity chromatography on collagen-polyacrylamide gel. The collagenase, when partially purified, was found to have an approximate molecular weight of 50,000. The purified enzyme contained no caseinolytic activity. On polyacrylamide gel electrophoresis, the purified enzyme gave a single protein band. The purified collagenase cleaved native acid-soluble guinea pig skin collagen at 37 degrees C with a pH optimum of 8. The enzyme was inhibited by EDTA, cysteine, and human serum but not by soybean trypsin inhibitor. Heparin did not stimulate the enzyme activity. Purified collagenase reduced the specific viscosity of native acid-soluble guinea pig skin collagen to 50 per cent of its original value at 27 degrees C. Polyacrylamide gel disc electrophoresis of the reaction products showed bands corresponding to alphaA, betaA, and alphaB fragments. Electron microscopic examination of SLS aggregates of the reaction products showed that the cleavage site by the enzyme was at a point 75 per cent from the \"A\" end (TCA75) and 25 per cent from the \"B\" end (TCB25) of the collagen molecule.", "contents": "Collagenase of human skin basal cell epithelioma. Collagenase of human basal cell epithelioma was purified by sequential ammonium sulfate precipitation, Sephadex gel filtration and affinity chromatography on collagen-polyacrylamide gel. The collagenase, when partially purified, was found to have an approximate molecular weight of 50,000. The purified enzyme contained no caseinolytic activity. On polyacrylamide gel electrophoresis, the purified enzyme gave a single protein band. The purified collagenase cleaved native acid-soluble guinea pig skin collagen at 37 degrees C with a pH optimum of 8. The enzyme was inhibited by EDTA, cysteine, and human serum but not by soybean trypsin inhibitor. Heparin did not stimulate the enzyme activity. Purified collagenase reduced the specific viscosity of native acid-soluble guinea pig skin collagen to 50 per cent of its original value at 27 degrees C. Polyacrylamide gel disc electrophoresis of the reaction products showed bands corresponding to alphaA, betaA, and alphaB fragments. Electron microscopic examination of SLS aggregates of the reaction products showed that the cleavage site by the enzyme was at a point 75 per cent from the \"A\" end (TCA75) and 25 per cent from the \"B\" end (TCB25) of the collagen molecule."}
{"id": "PMID:19453", "title": "alpha-chymotrypsin-catalyzed hydrolysis of phenyl acetate. Large Hammett's rho constant and participation of histidine-acylated intermediate.", "content": "A detailed examination of the mechanism of the hydrolysis of phenyl acetates by alpha-chymotrypsin [EC 3.4.21.1] was carried out. The effective deacylation rate constants of some phenyl acetates obtained by titration of the acetyl-enzyme decreased at low substrate concentrations and showed anomalous pH dependences and solvent isotope effects. The transient kinetics of deacylation of the acetyl-enzyme were biphasic. A spectrum and a breakdown rate similar to those of acetylimidazole were observed when the acetyl-enzyme was denaturated with sodium dodecyl sulfate. These results indicate the participation of histidine-acylated enzyme, which woud account for the anomalous phenomena previously found in this system, including a large value of Hammett's rho. The relation between the substrate activation and the two intermediates is discussed.", "contents": "alpha-chymotrypsin-catalyzed hydrolysis of phenyl acetate. Large Hammett's rho constant and participation of histidine-acylated intermediate. A detailed examination of the mechanism of the hydrolysis of phenyl acetates by alpha-chymotrypsin [EC 3.4.21.1] was carried out. The effective deacylation rate constants of some phenyl acetates obtained by titration of the acetyl-enzyme decreased at low substrate concentrations and showed anomalous pH dependences and solvent isotope effects. The transient kinetics of deacylation of the acetyl-enzyme were biphasic. A spectrum and a breakdown rate similar to those of acetylimidazole were observed when the acetyl-enzyme was denaturated with sodium dodecyl sulfate. These results indicate the participation of histidine-acylated enzyme, which woud account for the anomalous phenomena previously found in this system, including a large value of Hammett's rho. The relation between the substrate activation and the two intermediates is discussed."}
{"id": "PMID:19454", "title": "The occurence of a neutral protease and its inhibitor in rat peritoneal macrophages.", "content": "The lysate of the glycogen-induced macrophages in rat peritoneal exudate was fractionated by centrifugation and extraction into a water extract, 1 M KCl extract and residue fractions. Approximately 50% of the neutral protease activity toward casein in the lysate was recovered in the KCl extract fraction, which was practically devoid of acid protease, cathepsin D. The pH optimum of the neutral protease toward casein and urea-denatured hemoglobin was pH 8.5. The activity was inhibited strongly by DFP or chymostatin and only partially by HgCl2 or PCMB. Addition of a salt to the reaction medium caused enhancement of the activity with an optimum concentration of 0.25 M: KCl, KBr, KI, NaCl, NaBr, NaI, and MgCl2 were all almost equally effective. When the enzyme preparation was filtered through a column of Sephadex G-75 gel in the presence of 1 M KCl, a larger molecular weight fraction at the void volume was obtained in addition to a smaller molecular weight fraction showing a caseinolytic activity insensitive to KCl concentration. The former was found to have a specific inhibitory effect on the latter activity.", "contents": "The occurence of a neutral protease and its inhibitor in rat peritoneal macrophages. The lysate of the glycogen-induced macrophages in rat peritoneal exudate was fractionated by centrifugation and extraction into a water extract, 1 M KCl extract and residue fractions. Approximately 50% of the neutral protease activity toward casein in the lysate was recovered in the KCl extract fraction, which was practically devoid of acid protease, cathepsin D. The pH optimum of the neutral protease toward casein and urea-denatured hemoglobin was pH 8.5. The activity was inhibited strongly by DFP or chymostatin and only partially by HgCl2 or PCMB. Addition of a salt to the reaction medium caused enhancement of the activity with an optimum concentration of 0.25 M: KCl, KBr, KI, NaCl, NaBr, NaI, and MgCl2 were all almost equally effective. When the enzyme preparation was filtered through a column of Sephadex G-75 gel in the presence of 1 M KCl, a larger molecular weight fraction at the void volume was obtained in addition to a smaller molecular weight fraction showing a caseinolytic activity insensitive to KCl concentration. The former was found to have a specific inhibitory effect on the latter activity."}
{"id": "PMID:19455", "title": "Interactions of alpha-chymotrypsin with peptides containing tryptophan or its derivatives at the C-terminus.", "content": "The interaction between alpha-chymotrypsin [EC 3.4.21.1] and peptide substrate or peptide inhibitor was investigated to determine how the secondary interaction influences the rate of hydrolysis or the binding and whether or not its effect is variable with alteration of the P1 residue which interacts with the specificity determining site of the enzyme. Kinetic analysis was carried out at pH 6.5 and 7.8 for substrates of the type Ac-Glyn-X-OMe and for inhibitors of the type Ac-Glyn-X-OH where X denotes tryptophan or its derivatives. With substrates containing tryptophan or Nin-formyltryptophan, the second-order rate of hydrolysis increases with increase of chain length. With substrates containing 2-(2-nitro-4-carboxyphenylsulfenyl)-tryptophan, however, the rate of hydrolysis decreases with elongation of the chain, due to an increase in Km(app). The corresponding inhibitors behave differently from the other series of inhibitors at pH 6.5. The results indicate that the influence of the secondary interaction on reactivity or binding is related to the structural features of the P1 residue.", "contents": "Interactions of alpha-chymotrypsin with peptides containing tryptophan or its derivatives at the C-terminus. The interaction between alpha-chymotrypsin [EC 3.4.21.1] and peptide substrate or peptide inhibitor was investigated to determine how the secondary interaction influences the rate of hydrolysis or the binding and whether or not its effect is variable with alteration of the P1 residue which interacts with the specificity determining site of the enzyme. Kinetic analysis was carried out at pH 6.5 and 7.8 for substrates of the type Ac-Glyn-X-OMe and for inhibitors of the type Ac-Glyn-X-OH where X denotes tryptophan or its derivatives. With substrates containing tryptophan or Nin-formyltryptophan, the second-order rate of hydrolysis increases with increase of chain length. With substrates containing 2-(2-nitro-4-carboxyphenylsulfenyl)-tryptophan, however, the rate of hydrolysis decreases with elongation of the chain, due to an increase in Km(app). The corresponding inhibitors behave differently from the other series of inhibitors at pH 6.5. The results indicate that the influence of the secondary interaction on reactivity or binding is related to the structural features of the P1 residue."}
{"id": "PMID:19457", "title": "Purification and properties of aldehyde dehydrogenase from Saccharomyces cerevisiae.", "content": "A procedure for the purification of aldehyde dehydrogenase from bakers' yeast (Saccharomyces cerevisiae) is reported. Treatment with acid, heat and organic solvents was avoided and chromatographic and filtration techniques in the presence of phenylmethylsulfonylfluoride were mainly used. An affinity chromatography step using the reactive dye Cibacron blue F3G-A, which was covalently bound to Sepharose 4B, was found to be essential. The enzyme was bound to and then released from the dye. The purified enzyme was shown to be homogeneous by gel filtration, disc electrophoresis and SDS electrophoresis. The molecular weight of the purified enzyme determined by gel filtration was 170,000, which agreed with that of the enzyme in the crude extract. The enzyme was composed of subunits of a molecular weight of 57,000. The specific activity of the enzyme was 20 units per mg of protein under the standard assay conditions. The substrate specificity, the relative maximal velocity, the michaelis constants, the pH optimum, the stability and the activation energy of the enzyme are reported.", "contents": "Purification and properties of aldehyde dehydrogenase from Saccharomyces cerevisiae. A procedure for the purification of aldehyde dehydrogenase from bakers' yeast (Saccharomyces cerevisiae) is reported. Treatment with acid, heat and organic solvents was avoided and chromatographic and filtration techniques in the presence of phenylmethylsulfonylfluoride were mainly used. An affinity chromatography step using the reactive dye Cibacron blue F3G-A, which was covalently bound to Sepharose 4B, was found to be essential. The enzyme was bound to and then released from the dye. The purified enzyme was shown to be homogeneous by gel filtration, disc electrophoresis and SDS electrophoresis. The molecular weight of the purified enzyme determined by gel filtration was 170,000, which agreed with that of the enzyme in the crude extract. The enzyme was composed of subunits of a molecular weight of 57,000. The specific activity of the enzyme was 20 units per mg of protein under the standard assay conditions. The substrate specificity, the relative maximal velocity, the michaelis constants, the pH optimum, the stability and the activation energy of the enzyme are reported."}
{"id": "PMID:19458", "title": "Effects of phthalate esters on the latent ATPase and swelling of mitochondria.", "content": "Phthalate esters have shown to stimulate the latent ATPase [EC 3.6.1.3] activity and induce mitochondrial swelling. Among the tested phthalate esters, di-n-butyl phthalate (DBP) exhibited the greatest activity, and the activity decreased progressively as the alkyl chain was lengthened or shortened. The DBP-stimulated ATPase was oligomycin-sensitive. The degree of stimulation of the ATPase was proportional to the extent of mitochondrial swelling induced by DBP in 0.1 M Tris-HCl (pH 7.2) containing 0.25 M sucrose. However, the swelling was dependent on the tonicity of the solution or the concentration of chloride ions, while the stimulation of ATPase was independent of these factors. Swelling was strongly induced by DBP at slightly acidic rather than neutral or alkaline pH. The pH-activity curve of DBP-stimulated ATPase was in inverse correlation with that of swelling, which showed a rather flat maximum at pH 8.0. When bovine serum albumin (BSA) was added to a solution containing mitochondria before addition of DBP, swelling was no longer caused by DBP, though the latent ATPase was stimulated to the same extent in the absence of added BSA.", "contents": "Effects of phthalate esters on the latent ATPase and swelling of mitochondria. Phthalate esters have shown to stimulate the latent ATPase [EC 3.6.1.3] activity and induce mitochondrial swelling. Among the tested phthalate esters, di-n-butyl phthalate (DBP) exhibited the greatest activity, and the activity decreased progressively as the alkyl chain was lengthened or shortened. The DBP-stimulated ATPase was oligomycin-sensitive. The degree of stimulation of the ATPase was proportional to the extent of mitochondrial swelling induced by DBP in 0.1 M Tris-HCl (pH 7.2) containing 0.25 M sucrose. However, the swelling was dependent on the tonicity of the solution or the concentration of chloride ions, while the stimulation of ATPase was independent of these factors. Swelling was strongly induced by DBP at slightly acidic rather than neutral or alkaline pH. The pH-activity curve of DBP-stimulated ATPase was in inverse correlation with that of swelling, which showed a rather flat maximum at pH 8.0. When bovine serum albumin (BSA) was added to a solution containing mitochondria before addition of DBP, swelling was no longer caused by DBP, though the latent ATPase was stimulated to the same extent in the absence of added BSA."}
{"id": "PMID:19459", "title": "Properties of soluble rat brain histone lysine methyltransferase.", "content": "Histone-lysine methyltransferase has been solubilized from rat brain chromatin by repeated extraction with distilled water. The enzyme was further purified by chromatography on DEAE-cellulose and gel filtration. With chromosomal-bound histones as substrates, the enzyme methylated only the lysyl residues in histones H3 and H4. The ratio of N epsilon-mono-: N epsilon-di-: N epsilon-trimethyllysine in histone H3 was 1.8:1.0:0.45 and the ratio of N epsilon-mono-: N epsilon-dimethyllysine in histone H4 was 0.7:1.0. The enzyme loses specificity with soluble histones as substrates; however, histones H3 and H4 were still the best methyl acceptors. The pH optima for the enzyme with soluble histones H3 and H4 as substrates were 8.2 to 8.7 and 7.2 to 8.0, respectively. S-Adenosyl-L-homocysteine, one of the products of the reaction, was a competitive inhibitor with respect to S-adenosyl-L-methionine.", "contents": "Properties of soluble rat brain histone lysine methyltransferase. Histone-lysine methyltransferase has been solubilized from rat brain chromatin by repeated extraction with distilled water. The enzyme was further purified by chromatography on DEAE-cellulose and gel filtration. With chromosomal-bound histones as substrates, the enzyme methylated only the lysyl residues in histones H3 and H4. The ratio of N epsilon-mono-: N epsilon-di-: N epsilon-trimethyllysine in histone H3 was 1.8:1.0:0.45 and the ratio of N epsilon-mono-: N epsilon-dimethyllysine in histone H4 was 0.7:1.0. The enzyme loses specificity with soluble histones as substrates; however, histones H3 and H4 were still the best methyl acceptors. The pH optima for the enzyme with soluble histones H3 and H4 as substrates were 8.2 to 8.7 and 7.2 to 8.0, respectively. S-Adenosyl-L-homocysteine, one of the products of the reaction, was a competitive inhibitor with respect to S-adenosyl-L-methionine."}
{"id": "PMID:19462", "title": "Investigation of the relation of the pH-dependent dissociation of malate dehydrogenase to modification of the enzyme by N-ethylmaleimide.", "content": "The pH-dependent dissociation of porcine heart mitochondrial malate dehydrogenase (L-malate:NAD+ oxidoreductase, EC 1.1.1.37) has been further characterized using the technique of sedimentation velocity ultracentrifugation. The increased rate and specificity of the inactivation of mitochondrial malate dehydrogenase by the sulfhydryl reagent N-ethylmaleimide has been correlated with the pH-dependent dissociation of the enzyme. Data obtained using NAD+ and its component parts to reassociate the enzyme and also to protect the enzyme from inactivation by N-ethylmaleimide suggest that the sulfhydryl residues being modified by N-ethylmaleimide are inaccessible when the enzyme is in its dimeric form. A dissociation curve for the pH-dependent dissociation suggests that a limited number of residues are being protonated concomitant with dissociation of the enzyme. An apparent pKa of 5.3 has been determined for this phenomenon. Studies using enzyme modified by the sulfhydryl reagent N-ethylmaleimide indicate that selective modification of essential sulfhydryl residues alters the proper binding of NADH.", "contents": "Investigation of the relation of the pH-dependent dissociation of malate dehydrogenase to modification of the enzyme by N-ethylmaleimide. The pH-dependent dissociation of porcine heart mitochondrial malate dehydrogenase (L-malate:NAD+ oxidoreductase, EC 1.1.1.37) has been further characterized using the technique of sedimentation velocity ultracentrifugation. The increased rate and specificity of the inactivation of mitochondrial malate dehydrogenase by the sulfhydryl reagent N-ethylmaleimide has been correlated with the pH-dependent dissociation of the enzyme. Data obtained using NAD+ and its component parts to reassociate the enzyme and also to protect the enzyme from inactivation by N-ethylmaleimide suggest that the sulfhydryl residues being modified by N-ethylmaleimide are inaccessible when the enzyme is in its dimeric form. A dissociation curve for the pH-dependent dissociation suggests that a limited number of residues are being protonated concomitant with dissociation of the enzyme. An apparent pKa of 5.3 has been determined for this phenomenon. Studies using enzyme modified by the sulfhydryl reagent N-ethylmaleimide indicate that selective modification of essential sulfhydryl residues alters the proper binding of NADH."}
{"id": "PMID:19463", "title": "Human kidney gamma-glutamyl transpeptidase. Catalytic properties, subunit structure, and localization of the gamma-glutamyl binding site on the light subunit.", "content": "Human kidney gamma-glutamyl transpeptidase has been purified by a procedure involving Lubrol extraction, acetone precipitation, treatment with bromelain, and column chromatography on DEAE-cellulose and Sephadex G-150. The final preparation is a glycoprotein (molecular weight of approximately 84,000) composed of two nonidentical glycopeptides (molecular weights of 62,000 and 22,000). The isozymic forms, separable by isoelectric focusing, have different contents of sialic acid. The utilization of L-glutamine (which is both a gamma-glutamyl donor and acceptor) is stimulated about 3-fold by maleate in contrast to 10-fold stimulation of glutamine utilization by the rat kidney enzyme. The gamma-glutamyl analogs, 6-diazo-5-oxo-L-norleucine (DON) and L-azaserine inactivate the human kidney enzyme with respect to its transpeptidase and hydrolase activities. Inactivation is prevented by gamma-glutamyl substrates (but not by acceptor substrates) and is accelerated by maleate. [14C]DON reacts covalently and stoichiometrically at the gamma-glutamyl site, which was localized to the light subunit of the enzyme. The light subunit of human transpeptidase closely resembles that of rat kidney enzyme in having the gamma-glutamyl binding site, and similar molecular weight and amino acid composition. The heavy subunits of the two enzymes are markedly different in both molecular weight and amino acid content; this may account for differences observed in acceptor amino acid specificity and in the magnitude of the maleate effect.", "contents": "Human kidney gamma-glutamyl transpeptidase. Catalytic properties, subunit structure, and localization of the gamma-glutamyl binding site on the light subunit. Human kidney gamma-glutamyl transpeptidase has been purified by a procedure involving Lubrol extraction, acetone precipitation, treatment with bromelain, and column chromatography on DEAE-cellulose and Sephadex G-150. The final preparation is a glycoprotein (molecular weight of approximately 84,000) composed of two nonidentical glycopeptides (molecular weights of 62,000 and 22,000). The isozymic forms, separable by isoelectric focusing, have different contents of sialic acid. The utilization of L-glutamine (which is both a gamma-glutamyl donor and acceptor) is stimulated about 3-fold by maleate in contrast to 10-fold stimulation of glutamine utilization by the rat kidney enzyme. The gamma-glutamyl analogs, 6-diazo-5-oxo-L-norleucine (DON) and L-azaserine inactivate the human kidney enzyme with respect to its transpeptidase and hydrolase activities. Inactivation is prevented by gamma-glutamyl substrates (but not by acceptor substrates) and is accelerated by maleate. [14C]DON reacts covalently and stoichiometrically at the gamma-glutamyl site, which was localized to the light subunit of the enzyme. The light subunit of human transpeptidase closely resembles that of rat kidney enzyme in having the gamma-glutamyl binding site, and similar molecular weight and amino acid composition. The heavy subunits of the two enzymes are markedly different in both molecular weight and amino acid content; this may account for differences observed in acceptor amino acid specificity and in the magnitude of the maleate effect."}
{"id": "PMID:19464", "title": "Steady state and equilibrium exchange kinetic studies of the sheep brain glutamine synthetase reaction.", "content": "The kinetic mechanism of the sheep brain glutamine synthetase has been examined by both initial rate kinetics using the glutamate analog beta-glutamate and by isotope exchange measurements at equilibrium. Results of the initial rate studies were compatible with a number of sequential mechanisms but not with a partially or fully ordered rapid equilibrium or a ping-pong mechanism. Kinetic parameters at 37 degrees and pH 7.2 were K beta-Glu = 16 mM, KATP = 0.28 mM, and KNH2OH = 1.4 mM. For all equilibrium exchanges studied (ATP in equilibrium ADP, ATP in equilibrium Pi, and Glu in equilibrium Gln), the rate of exchange rose smoothly to a maximum as all substrates and products were simultaneously raised in a constant ratio. This result is in accord with a random order of substrate addition. A brief treatment of equilibrium exchange rates in cases where all substrate/product pairs are varied together is also presented.", "contents": "Steady state and equilibrium exchange kinetic studies of the sheep brain glutamine synthetase reaction. The kinetic mechanism of the sheep brain glutamine synthetase has been examined by both initial rate kinetics using the glutamate analog beta-glutamate and by isotope exchange measurements at equilibrium. Results of the initial rate studies were compatible with a number of sequential mechanisms but not with a partially or fully ordered rapid equilibrium or a ping-pong mechanism. Kinetic parameters at 37 degrees and pH 7.2 were K beta-Glu = 16 mM, KATP = 0.28 mM, and KNH2OH = 1.4 mM. For all equilibrium exchanges studied (ATP in equilibrium ADP, ATP in equilibrium Pi, and Glu in equilibrium Gln), the rate of exchange rose smoothly to a maximum as all substrates and products were simultaneously raised in a constant ratio. This result is in accord with a random order of substrate addition. A brief treatment of equilibrium exchange rates in cases where all substrate/product pairs are varied together is also presented."}
{"id": "PMID:19467", "title": "Purified proton conductor in proton translocating adenosine triphosphatase of a thermophilic bacterium.", "content": "1. The membrane-integrated portion (TF0) of the proton translocating ATPase complex (TF0-F1) of the thermophilic bacterium PS3 was highly purified. Its proton-conducting activity was investigated in vesicles reconstituted from TF0 and phospholipids (TF0 vesicles). 2. The rate of proton conduction through TF0 was proportional to the membrane potential imposed (6H+ uptake/s/TF0 molecule with 103 mV at pH 8.0). The pH profile of the rate revealed that a proton, not a hydroxy ion, was the true substrate conducted and that there was a monoprotic proton binding site in TF0 (pKa = 6.8). The temperature coefficient of proton conductance of TF0 showed a considerable variation depending on the phospholipids of the vesicles with respective transition temperatures. 3. Passive proton conduction through TF0 was inhibited stoichiometrically by addition of either the soluble ATPase portion (TF1) of TF0-F1, or an energy transfer inhibitor dicyclohexylcarbodiimide or an antibody against TF0. 4. The proton conductance of TF0 was concluded to represent its intrinsic activity in the original TF0-F1 complex.", "contents": "Purified proton conductor in proton translocating adenosine triphosphatase of a thermophilic bacterium. 1. The membrane-integrated portion (TF0) of the proton translocating ATPase complex (TF0-F1) of the thermophilic bacterium PS3 was highly purified. Its proton-conducting activity was investigated in vesicles reconstituted from TF0 and phospholipids (TF0 vesicles). 2. The rate of proton conduction through TF0 was proportional to the membrane potential imposed (6H+ uptake/s/TF0 molecule with 103 mV at pH 8.0). The pH profile of the rate revealed that a proton, not a hydroxy ion, was the true substrate conducted and that there was a monoprotic proton binding site in TF0 (pKa = 6.8). The temperature coefficient of proton conductance of TF0 showed a considerable variation depending on the phospholipids of the vesicles with respective transition temperatures. 3. Passive proton conduction through TF0 was inhibited stoichiometrically by addition of either the soluble ATPase portion (TF1) of TF0-F1, or an energy transfer inhibitor dicyclohexylcarbodiimide or an antibody against TF0. 4. The proton conductance of TF0 was concluded to represent its intrinsic activity in the original TF0-F1 complex."}
{"id": "PMID:19468", "title": "Manganese cytochrome c. Structure and properties.", "content": "Oxidized and reduced manganese cytochromes c, Mn Cyt c+ and Mn Cyt c, have been synthesized. Mn Cyt c+ and Fe Cyt c+ have identical electrophoretic and ion exchange mobilities. Mn Cyt c+ does not bind F-, CN-, or N3- ions; Mn Cyt c does not bind CO or O2. Mn Cyt c is very rapidly autooxidized by O2 even at -50 degrees. The manganese ion is readily dissociated from Mn Cyt c at acidic pH values. Both Mn Cyt c and Mn Cyt c+ are high spin complexes with 3d5 S = 5/2 and 3d4 S = 2 electronic configurations, respectively. The epr spectrum of Mn Cyt c is rhombic with (formula: see text). Both oxidized and reduced Mn Cyt c react with NO; the former reaction is reversible and the product has the following epr spectral parameters: (formula: see text). There is no superhyperfine interaction observable with the NO ligand, and the unpaired electron density is estimated to be mostly in the metal ion d xy orbital. The structure is best formulated as Mn Cyt c (NO)+. The half-reduction potential of Mn Cyt c is + 60 +/- 40 mV. It is neither oxidized by cytochrome oxidase nor reduced by NADH, NADPH, or succinate cytochrome reductase. These physical, chemical, and enzymic properties of manganese cytochromes c suggest a five-coordinate metalloporphyrin prosthetic group with the manganese ion situated significantly out-of-plane toward the side of His-18.", "contents": "Manganese cytochrome c. Structure and properties. Oxidized and reduced manganese cytochromes c, Mn Cyt c+ and Mn Cyt c, have been synthesized. Mn Cyt c+ and Fe Cyt c+ have identical electrophoretic and ion exchange mobilities. Mn Cyt c+ does not bind F-, CN-, or N3- ions; Mn Cyt c does not bind CO or O2. Mn Cyt c is very rapidly autooxidized by O2 even at -50 degrees. The manganese ion is readily dissociated from Mn Cyt c at acidic pH values. Both Mn Cyt c and Mn Cyt c+ are high spin complexes with 3d5 S = 5/2 and 3d4 S = 2 electronic configurations, respectively. The epr spectrum of Mn Cyt c is rhombic with (formula: see text). Both oxidized and reduced Mn Cyt c react with NO; the former reaction is reversible and the product has the following epr spectral parameters: (formula: see text). There is no superhyperfine interaction observable with the NO ligand, and the unpaired electron density is estimated to be mostly in the metal ion d xy orbital. The structure is best formulated as Mn Cyt c (NO)+. The half-reduction potential of Mn Cyt c is + 60 +/- 40 mV. It is neither oxidized by cytochrome oxidase nor reduced by NADH, NADPH, or succinate cytochrome reductase. These physical, chemical, and enzymic properties of manganese cytochromes c suggest a five-coordinate metalloporphyrin prosthetic group with the manganese ion situated significantly out-of-plane toward the side of His-18."}
{"id": "PMID:19470", "title": "Cobalt-substituted horseradish peroxidase.", "content": "Horseradish peroxidase can be reconstituted with cobalt porphyrin to give a cobaltic holoenzyme having physicochemical properties quite similar to those of the native ferric protein. The cobaltic protein (Co3+HRP) can be reduced to the cobaltous form (CoHRP), the analogue of ferroperoxidase and the reduced cobalt protein can bind O2 to form an analogue of oxyferroperoxidase (Compound III). Since both the CoHRP and oxy-CoHRP are EPR-visible, the cobalt has been used to probe the nature of the heme crevice in these two protein forms. The occurrence of a three-line 14N superhyperfine pattern in the spectrum of the former unambiguously shows that in the divalent state of the protein the proximal axial ligand is a nitrogenous base. The spectrum of the latter shows a uniquely large Aparallel(59Co) = 23.2 G. Although we confirm the reported failure of the Co3+HRP to catalyze peroxide-dependent oxidations of classical peroxidase substrates (Gjessing, E.C., and Sumner, J.B. (1942) Arch. Biochem. 1, 1), the oxy-CoHRP does undergo oxidation-reduction reactions analogous to those exhibited in the cytochrome P-450 catalytic cycle.", "contents": "Cobalt-substituted horseradish peroxidase. Horseradish peroxidase can be reconstituted with cobalt porphyrin to give a cobaltic holoenzyme having physicochemical properties quite similar to those of the native ferric protein. The cobaltic protein (Co3+HRP) can be reduced to the cobaltous form (CoHRP), the analogue of ferroperoxidase and the reduced cobalt protein can bind O2 to form an analogue of oxyferroperoxidase (Compound III). Since both the CoHRP and oxy-CoHRP are EPR-visible, the cobalt has been used to probe the nature of the heme crevice in these two protein forms. The occurrence of a three-line 14N superhyperfine pattern in the spectrum of the former unambiguously shows that in the divalent state of the protein the proximal axial ligand is a nitrogenous base. The spectrum of the latter shows a uniquely large Aparallel(59Co) = 23.2 G. Although we confirm the reported failure of the Co3+HRP to catalyze peroxide-dependent oxidations of classical peroxidase substrates (Gjessing, E.C., and Sumner, J.B. (1942) Arch. Biochem. 1, 1), the oxy-CoHRP does undergo oxidation-reduction reactions analogous to those exhibited in the cytochrome P-450 catalytic cycle."}
{"id": "PMID:19472", "title": "Purification from hamster cells of the multifunctional protein that initiates de novo synthesis of pyrimidine nucleotides.", "content": "Carbamyl-P synthetase (EC 2.7.2.9), aspartate transcarbamylase (EC 2.1.3.2), and dihydro-orotase (EC 3.5.2.3), the first three enzymes of the de novo pathway for synthesis of pyrimidine nucleotides, have been co-purified as a single oligomeric protein from a mutant line of hamster cells selected for its ability to resist N-(phosphonacetyl)-L-aspartate (PALA), a potent and specific inhibitor of aspartate transcarbamylase. All three enzymes overaccum,late in the mutant cells (Kempe, T.D., Swyryd, E.A., Bruist, M., and Stark, G.R. (1976) Cell 9, 541-550) and the oligomer represents nearly 10% of the total cellular protein. Tens of milligrams of oligomer have been purified to homogeneity by a simple and rapid procedure, with recovery of about 50% of all three activities. The pure protein contains only one size of polypeptide, Mr approximately 200,000, as revealed by electrophoresis in danaturing gels. All three enzyme activities are associated with this polypeptide, indicating that it is multifunctional. Further evidence for a multifunctional protein is provided by titration of the oligomer with radioactive PALA, which reveals that the number of PALA binding sites approximately equals the number of polypeptide chains. The isolated multifunctional protein is a mixture of trimers and hexamers.", "contents": "Purification from hamster cells of the multifunctional protein that initiates de novo synthesis of pyrimidine nucleotides. Carbamyl-P synthetase (EC 2.7.2.9), aspartate transcarbamylase (EC 2.1.3.2), and dihydro-orotase (EC 3.5.2.3), the first three enzymes of the de novo pathway for synthesis of pyrimidine nucleotides, have been co-purified as a single oligomeric protein from a mutant line of hamster cells selected for its ability to resist N-(phosphonacetyl)-L-aspartate (PALA), a potent and specific inhibitor of aspartate transcarbamylase. All three enzymes overaccum,late in the mutant cells (Kempe, T.D., Swyryd, E.A., Bruist, M., and Stark, G.R. (1976) Cell 9, 541-550) and the oligomer represents nearly 10% of the total cellular protein. Tens of milligrams of oligomer have been purified to homogeneity by a simple and rapid procedure, with recovery of about 50% of all three activities. The pure protein contains only one size of polypeptide, Mr approximately 200,000, as revealed by electrophoresis in danaturing gels. All three enzyme activities are associated with this polypeptide, indicating that it is multifunctional. Further evidence for a multifunctional protein is provided by titration of the oligomer with radioactive PALA, which reveals that the number of PALA binding sites approximately equals the number of polypeptide chains. The isolated multifunctional protein is a mixture of trimers and hexamers."}
{"id": "PMID:19473", "title": "Activation by phosphate of yeast phosphofructokinase.", "content": "The activity of yeast phosphofructokinase assayed in vitro at physiological concentrations of known substrates and effectors is 100-fold lower than the glycolytic flux observed in vivo. Phosphate synergistically with AMP activates the enzyme to a level within the range of the physiological needs. The activation by phosphate is pH-dependent: the activation is 100-fold at pH 6.4 while no effect is observed at pH 7.5. The activation by AMP, phosphate, or both together is primarily due to changes in the affinity of the enzyme for fructose-6-P. Under conditions similar to those prevailing in glycolysing yeast (pH 6.4, 1 mM ATP, 10 mM NH4+) the apparent affinity constant for fructose-6-P (S0.5) decreases from 3 to 1.4 mM upon addition of 1 mM AMP or 10 mM phosphate; if both activators are present together, S0.5 is further decreased to 0.2 mM. In all cases the cooperativity toward fructose-6-P remains unchanged. These results are consistent with a model for phosphofructokinase where two conformations, with different affinities for fructose-6-P and ATP, will present the same affinity for AMP and phosphate. AMP would diminish the affinity for ATP at the regulatory site and phosphate would increase the affinity for fructose-6-P. The results obtained indicate that the activity of phosphofructokinase in the shift glycolysis-gluconeogenesis is mainly regulated by changes in the concentration of fructose-6-P.", "contents": "Activation by phosphate of yeast phosphofructokinase. The activity of yeast phosphofructokinase assayed in vitro at physiological concentrations of known substrates and effectors is 100-fold lower than the glycolytic flux observed in vivo. Phosphate synergistically with AMP activates the enzyme to a level within the range of the physiological needs. The activation by phosphate is pH-dependent: the activation is 100-fold at pH 6.4 while no effect is observed at pH 7.5. The activation by AMP, phosphate, or both together is primarily due to changes in the affinity of the enzyme for fructose-6-P. Under conditions similar to those prevailing in glycolysing yeast (pH 6.4, 1 mM ATP, 10 mM NH4+) the apparent affinity constant for fructose-6-P (S0.5) decreases from 3 to 1.4 mM upon addition of 1 mM AMP or 10 mM phosphate; if both activators are present together, S0.5 is further decreased to 0.2 mM. In all cases the cooperativity toward fructose-6-P remains unchanged. These results are consistent with a model for phosphofructokinase where two conformations, with different affinities for fructose-6-P and ATP, will present the same affinity for AMP and phosphate. AMP would diminish the affinity for ATP at the regulatory site and phosphate would increase the affinity for fructose-6-P. The results obtained indicate that the activity of phosphofructokinase in the shift glycolysis-gluconeogenesis is mainly regulated by changes in the concentration of fructose-6-P."}
{"id": "PMID:19475", "title": "Purification and properties of a T4 bacteriophage factor that modifies valyl-tRNA synthetase of Escherichia coli.", "content": "After T4 bacteriophage infects Escherichia coli, a peptide tau, produced under the control of a phage gene, binds to the host valyl transfer ribonucleic acid synthetase (EC 6.1.1.9) and thereby changes several of its physicochemical properties. The interaction of tau with the host enzyme was investigated in vitro after extensively purifying the factor from T4-infected E. coli using a rapid purification procedure. The tau preparation migrated as a single, protein-staining band with a molecular weight of 11,000 during sodium dodecyl sulfate-gel electrophoresis. The purified peptide completely converted partially purified valyl-tRNA synthetase from uninfected E. coli into the form present in cell-free extracts prepared from virus-infected bacteria. The enzyme modified in vitro also exhibited the enhanced affinity for tRNA characteristic of the viral form of valyl-tRNA synthetase. The addition of bulk tRNA from E. coli B, tRNAVal, or tRNA1Val to enzyme modified in vitro increased its sedimentation rate to that of enzyme prepared from phage-infected cells. Amino acid analysis of the purified tau peptide revealed a relatively high concentration of the amino acids lysine and alanine, and a lack of detectable proline, tyrosine, phenylalanine, and methionine.", "contents": "Purification and properties of a T4 bacteriophage factor that modifies valyl-tRNA synthetase of Escherichia coli. After T4 bacteriophage infects Escherichia coli, a peptide tau, produced under the control of a phage gene, binds to the host valyl transfer ribonucleic acid synthetase (EC 6.1.1.9) and thereby changes several of its physicochemical properties. The interaction of tau with the host enzyme was investigated in vitro after extensively purifying the factor from T4-infected E. coli using a rapid purification procedure. The tau preparation migrated as a single, protein-staining band with a molecular weight of 11,000 during sodium dodecyl sulfate-gel electrophoresis. The purified peptide completely converted partially purified valyl-tRNA synthetase from uninfected E. coli into the form present in cell-free extracts prepared from virus-infected bacteria. The enzyme modified in vitro also exhibited the enhanced affinity for tRNA characteristic of the viral form of valyl-tRNA synthetase. The addition of bulk tRNA from E. coli B, tRNAVal, or tRNA1Val to enzyme modified in vitro increased its sedimentation rate to that of enzyme prepared from phage-infected cells. Amino acid analysis of the purified tau peptide revealed a relatively high concentration of the amino acids lysine and alanine, and a lack of detectable proline, tyrosine, phenylalanine, and methionine."}
{"id": "PMID:19477", "title": "A sodium-specific membrane permeability defect induced by phospholipid vesicle treatment of erythrocytes.", "content": "Treatment of human erythrocytes with phospholipid vesicles induces a selective membrane permeability defect which leads to osmotic lysis. The defective cells exhibit a massive sodium ion leak while maintaining normal impermeability to other cations, anions, and neutral small molecules. The sodium ion influx and resulting hemolysis may be inhibited by increased pH, by tetrodotoxin, and by reintroduction of vesicle-extracted proteins into the cell. These characteristics suggest that phospholipid vesicle treatment destroys the cell by disrupting a membrane protein system involved in regulation of cation permeability.", "contents": "A sodium-specific membrane permeability defect induced by phospholipid vesicle treatment of erythrocytes. Treatment of human erythrocytes with phospholipid vesicles induces a selective membrane permeability defect which leads to osmotic lysis. The defective cells exhibit a massive sodium ion leak while maintaining normal impermeability to other cations, anions, and neutral small molecules. The sodium ion influx and resulting hemolysis may be inhibited by increased pH, by tetrodotoxin, and by reintroduction of vesicle-extracted proteins into the cell. These characteristics suggest that phospholipid vesicle treatment destroys the cell by disrupting a membrane protein system involved in regulation of cation permeability."}
{"id": "PMID:19480", "title": "Interrelationship of carbohydrate metabolism and alkaline phosphatase synthesis in Bacillus licheniformis 749/c.", "content": "Membrane-bound alkaline phosphatase of Bacillus licheniformis 749/c is derepressed by glucose in complex and chemically defined media. In the presence of lactate, pyruvate, or succinate the synthesis is repressed. The lactate repression neither affects total protein synthesis nor inhibits penicillinase synthesis. Thus, carbon sources specifically influence alkaline phosphatase synthesis. Although variations in the inorganic phosphate content of the growth media directly affect alkaline phosphatase synthesis, the intracellular inorganic and total phosphate pools appear to be unrelated to its repression or derepression. During lactate repression there is preferential incorporation of lactate molecules into glycogen, whereas no such incorporation could be detected from glucose. Net glycogen synthesis remains the same in glucose- or lactate-grown cells. It is postulated that, in phosphate-deficient growth medium, gluconeogenic metabolism regulates alkaline phosphatase synthesis.", "contents": "Interrelationship of carbohydrate metabolism and alkaline phosphatase synthesis in Bacillus licheniformis 749/c. Membrane-bound alkaline phosphatase of Bacillus licheniformis 749/c is derepressed by glucose in complex and chemically defined media. In the presence of lactate, pyruvate, or succinate the synthesis is repressed. The lactate repression neither affects total protein synthesis nor inhibits penicillinase synthesis. Thus, carbon sources specifically influence alkaline phosphatase synthesis. Although variations in the inorganic phosphate content of the growth media directly affect alkaline phosphatase synthesis, the intracellular inorganic and total phosphate pools appear to be unrelated to its repression or derepression. During lactate repression there is preferential incorporation of lactate molecules into glycogen, whereas no such incorporation could be detected from glucose. Net glycogen synthesis remains the same in glucose- or lactate-grown cells. It is postulated that, in phosphate-deficient growth medium, gluconeogenic metabolism regulates alkaline phosphatase synthesis."}
{"id": "PMID:19482", "title": "J. Edouard Samson Address: the autonomic nerve supply of bone. An experimental study of the intraosseous adrenergic nervi vasorum in the rabbit.", "content": "The anatomy of the autonomic sympathetic vasomotor nerve supply of bone was studied in rabbits by methods of histochemistry, and fluorescent and electron microscopy. Our observations show that the intraosseous vessels are richly supplied by adrenergic nerves. The large primary nerves are located on or about the surface of the vessel; the medium sized secondary nerves spiral around the long axis of vessels lying more deeply in the tunica adventitia; and the fine tertiary nerves form a rich plexus at the outer area of the tunica media. The tertiary nerves have various structures which probably contain neurotransmitter substance--that is, noradrenaline--and function as neuro-vasomuscular synapses. The sympathetic nerve supply of bone originates from the appropriate ganglion, and in the case of the tibial diaphysis it descends through the sciatic nerve and thereafter mainly through the medial popliteal nerve and enters the bone alongside the nutrient artery.", "contents": "J. Edouard Samson Address: the autonomic nerve supply of bone. An experimental study of the intraosseous adrenergic nervi vasorum in the rabbit. The anatomy of the autonomic sympathetic vasomotor nerve supply of bone was studied in rabbits by methods of histochemistry, and fluorescent and electron microscopy. Our observations show that the intraosseous vessels are richly supplied by adrenergic nerves. The large primary nerves are located on or about the surface of the vessel; the medium sized secondary nerves spiral around the long axis of vessels lying more deeply in the tunica adventitia; and the fine tertiary nerves form a rich plexus at the outer area of the tunica media. The tertiary nerves have various structures which probably contain neurotransmitter substance--that is, noradrenaline--and function as neuro-vasomuscular synapses. The sympathetic nerve supply of bone originates from the appropriate ganglion, and in the case of the tibial diaphysis it descends through the sciatic nerve and thereafter mainly through the medial popliteal nerve and enters the bone alongside the nutrient artery."}
{"id": "PMID:19483", "title": "Coordinate control of collagen synthesis and cell growth in chick embryo fibroblasts and the effect of viral transformation on collagen synthesis.", "content": "Using collagenase digestion as an assay for collagen in partially synchronized secondary cultures of chick embryo fibroblasts, we find that the rate of collagen synthesis remains at a constant fraction of overall protein synthesis (5%) regardless of the growth rate of the cells even when the rate of protein synthesis is accelerated 5-fold by adding serum and altering the pH of the culture medium. However, in cells oncogenically transformed by Rous sarcoma virus, the relative rate of collagen synthesis was decreased by 50% 24 hours after infection and was 10% of the initial rate after 5 days. This selective decrease in rate of collagen synthesis could be reversed in cells infected with an RSV temperature-sensitive transformation-defective mutant at the non-permissive temperature, indicating that the decrease in the rate of collagen synthesis was not merely the result of viral infection but was a direct consequence of oncogenic transformation.", "contents": "Coordinate control of collagen synthesis and cell growth in chick embryo fibroblasts and the effect of viral transformation on collagen synthesis. Using collagenase digestion as an assay for collagen in partially synchronized secondary cultures of chick embryo fibroblasts, we find that the rate of collagen synthesis remains at a constant fraction of overall protein synthesis (5%) regardless of the growth rate of the cells even when the rate of protein synthesis is accelerated 5-fold by adding serum and altering the pH of the culture medium. However, in cells oncogenically transformed by Rous sarcoma virus, the relative rate of collagen synthesis was decreased by 50% 24 hours after infection and was 10% of the initial rate after 5 days. This selective decrease in rate of collagen synthesis could be reversed in cells infected with an RSV temperature-sensitive transformation-defective mutant at the non-permissive temperature, indicating that the decrease in the rate of collagen synthesis was not merely the result of viral infection but was a direct consequence of oncogenic transformation."}
{"id": "PMID:19484", "title": "Effects of sugars on melanogenesis in cultured melanoma cells.", "content": "A permanent cell line C2M of mouse melanoma B16 was highly melanized in a modified Eagle's MEM supplemented with 10% calf serum, when the medium contained 1 mM galactose and 10 mM pyruvate instead of 5.5 mM glucose. The activity of the key anzyme for melanogenesis, tyrosinase (EC 1.14.18.1), of living cells cultured in the galactose-pyruvate medium was consistently 27 times higher than that of cells in normal MEM. This high level of tyrosinase activity was maintained in the stationary phase, in contrast to the activity of cells in normal medium, which decreased sharply in the stationary phase. It seems likely that tyrosinase activity is suppressed by the presence of glucose rather than stimulated by galactose. This modified medium should be useful obtaining a high level of tyrosinase activity in living cells in culture and in cell-free extracts.", "contents": "Effects of sugars on melanogenesis in cultured melanoma cells. A permanent cell line C2M of mouse melanoma B16 was highly melanized in a modified Eagle's MEM supplemented with 10% calf serum, when the medium contained 1 mM galactose and 10 mM pyruvate instead of 5.5 mM glucose. The activity of the key anzyme for melanogenesis, tyrosinase (EC 1.14.18.1), of living cells cultured in the galactose-pyruvate medium was consistently 27 times higher than that of cells in normal MEM. This high level of tyrosinase activity was maintained in the stationary phase, in contrast to the activity of cells in normal medium, which decreased sharply in the stationary phase. It seems likely that tyrosinase activity is suppressed by the presence of glucose rather than stimulated by galactose. This modified medium should be useful obtaining a high level of tyrosinase activity in living cells in culture and in cell-free extracts."}
{"id": "PMID:19485", "title": "The self-assembly of synthetic filaments of myosin isolated from Chaos carolinensis and Amoeba proteus.", "content": "Synthetic myosin thick filaments were formed from preparations of electrophoretically homogeneous myosin isolated from Chaos carolinensis and Amoeba proteus when dialysed to physiological ionic strength and pH. Myosin dialysed directly against low ionic strength buffers formed native-like thick filaments in the presence and absence of exogenous divalent cations. The average dimensions of the synthetic filaments grown under these conditions were 455 nm long and 16 nm wide with a distinct bare central zone 174 nm long. Myosin predialysed against EGTA-EDTA solutions at high ionic strength and then dialysed to low ionic strength formed native-like filaments only in the presence of 1mM Mg2+. 1 mM Ca2+ could not be substituted for Mg2+ under these conditions to achieve native-like filaments. Filaments grown from predialysed myosin in the absence of Mg2+ resembled EGTA-dissociated myosin filaments observed in EGTA-treated cytoplasm and were highly branched, poorly formed filaments lacking a distinct bare central zone. The average dimensions of the filaments grown from predialysed myosin in the absence of Mg2+ were 328 nm long, 13 nm wide with a bare central zone 111 nm long. Under the conditions tested, myosin isolated from these amoebae did not demonstrate a divalent cation requirement for thick filament formation. The results obtained with myosin isolated from the 2 organisms were identical.", "contents": "The self-assembly of synthetic filaments of myosin isolated from Chaos carolinensis and Amoeba proteus. Synthetic myosin thick filaments were formed from preparations of electrophoretically homogeneous myosin isolated from Chaos carolinensis and Amoeba proteus when dialysed to physiological ionic strength and pH. Myosin dialysed directly against low ionic strength buffers formed native-like thick filaments in the presence and absence of exogenous divalent cations. The average dimensions of the synthetic filaments grown under these conditions were 455 nm long and 16 nm wide with a distinct bare central zone 174 nm long. Myosin predialysed against EGTA-EDTA solutions at high ionic strength and then dialysed to low ionic strength formed native-like filaments only in the presence of 1mM Mg2+. 1 mM Ca2+ could not be substituted for Mg2+ under these conditions to achieve native-like filaments. Filaments grown from predialysed myosin in the absence of Mg2+ resembled EGTA-dissociated myosin filaments observed in EGTA-treated cytoplasm and were highly branched, poorly formed filaments lacking a distinct bare central zone. The average dimensions of the filaments grown from predialysed myosin in the absence of Mg2+ were 328 nm long, 13 nm wide with a bare central zone 111 nm long. Under the conditions tested, myosin isolated from these amoebae did not demonstrate a divalent cation requirement for thick filament formation. The results obtained with myosin isolated from the 2 organisms were identical."}
{"id": "PMID:19488", "title": "[Identification and quantitation of impurities from benorilate (Salipran) by high-performance liquid chromatography (author's transl)].", "content": "High-performance liquid chromatography is used for identification and quantitation of impurities which may be encountered in a new antalgic, benorilate (or Salipran), an ester of aspirin with paracetamol. Gradient elution is carried out using a stationary phase consisting of porous 10-micron silica beads bonded to alkylnitrile (Micropak CN), and a mixture of hexane-methylenechloride-methanol-acetic acid with varying methanol percentage as mobile phase. The following impurities were separated from benorilate: acetylsalicylic anhydride, aspirin, acetylsalicylsalicylic acid, salophene, amino-4-phenylacetoxy-2-benzoate, paracetamol, p-aminophenol. The repeatability of the quantitative analysis is good with a standard variation of 0.54% for benorilate (7 injections). Detection is by UV absorption at 254 nm, and detectability is between 2-10(-9) moles for p-aminophenol and 4-10(-11) moles for salophene.", "contents": "[Identification and quantitation of impurities from benorilate (Salipran) by high-performance liquid chromatography (author's transl)]. High-performance liquid chromatography is used for identification and quantitation of impurities which may be encountered in a new antalgic, benorilate (or Salipran), an ester of aspirin with paracetamol. Gradient elution is carried out using a stationary phase consisting of porous 10-micron silica beads bonded to alkylnitrile (Micropak CN), and a mixture of hexane-methylenechloride-methanol-acetic acid with varying methanol percentage as mobile phase. The following impurities were separated from benorilate: acetylsalicylic anhydride, aspirin, acetylsalicylsalicylic acid, salophene, amino-4-phenylacetoxy-2-benzoate, paracetamol, p-aminophenol. The repeatability of the quantitative analysis is good with a standard variation of 0.54% for benorilate (7 injections). Detection is by UV absorption at 254 nm, and detectability is between 2-10(-9) moles for p-aminophenol and 4-10(-11) moles for salophene."}
{"id": "PMID:19490", "title": "Purification of alpha-L-fucosidase from various sources by affinity chromatography.", "content": "An affinity column for alpha-L-fucosidases was constructed by linking p-amino-phenyl 1-thio-alpha-L-fucopyranoside to Sepharose 4B through linkers of succinyl 3,3'-diamino-dipropylamine. Excellent purification of alpha-L-fucosidase from rat epididymis, Clostridium perfringens and Limulus polyphemus (horse shoecrab) could be effected inone step with good yield. An affinity column purification step can be introduced at any point in published purification procedures. The purified enzyme is essentially free of other glycosidases and proteolytic enzymes. The column material is stable and can be reused for at least two years.", "contents": "Purification of alpha-L-fucosidase from various sources by affinity chromatography. An affinity column for alpha-L-fucosidases was constructed by linking p-amino-phenyl 1-thio-alpha-L-fucopyranoside to Sepharose 4B through linkers of succinyl 3,3'-diamino-dipropylamine. Excellent purification of alpha-L-fucosidase from rat epididymis, Clostridium perfringens and Limulus polyphemus (horse shoecrab) could be effected inone step with good yield. An affinity column purification step can be introduced at any point in published purification procedures. The purified enzyme is essentially free of other glycosidases and proteolytic enzymes. The column material is stable and can be reused for at least two years."}
{"id": "PMID:19492", "title": "Nickel gas chromatographic columns: an alternative to glass for biological samples.", "content": "Nickel tubing may be substituted for glass in the fabrication of gas chromatographic columns for use with samples of biological interest. Comparisons of separations of mixtures of steroids, narcotic alkaloids, phenothiazines, and amphetamines on stainless stell, glass, and nickel packed columns showed little or no observable sample decomposition on glass or nickel as contrasted to complete loss of certain compounds on stainless steel. The nickel columns are easily prepared, durable, economical, and not subject  to breakage.", "contents": "Nickel gas chromatographic columns: an alternative to glass for biological samples. Nickel tubing may be substituted for glass in the fabrication of gas chromatographic columns for use with samples of biological interest. Comparisons of separations of mixtures of steroids, narcotic alkaloids, phenothiazines, and amphetamines on stainless stell, glass, and nickel packed columns showed little or no observable sample decomposition on glass or nickel as contrasted to complete loss of certain compounds on stainless steel. The nickel columns are easily prepared, durable, economical, and not subject  to breakage."}
{"id": "PMID:19495", "title": "Analysis of water soluble vitamins by high pressure liquid chromatography.", "content": "Resolution of the water-soluble vitamins--pyridoxin, riboflavin, niacinamide, vitamin B12, thiamin, ascorbic acid, niacin and folic acid--by high pressure liquid chromatography was examined on two bonded-phase columns, muBondapak C18 and muBondapak NH2. The effect on the retention times of individual vitamins and the separation of a multivitamin sample was determined using varying proportions of water/methanol as the eluting solvent and by addition of various salts, buffer solutions and PIC reagents to the water/methanol. Each vitamin was able to be eluted satisfactorily from muBondapak C18. It was found that seven vitamins could be resolved from a multivitamin mixture in a single analysis in several solvent systems with the total time for the analyses being always less than 40 min. With muBondapak NH2, all the vitamins except folic acid were eluted and six vitamins could be resolved from a mixture in a single analysis. The speed of analysis was greater with muBondapak NH2 with all compounds eluted in 15 min and the peaks were sharper. The order of elution was essentially the reverse of that obtained with muBondapak C18.", "contents": "Analysis of water soluble vitamins by high pressure liquid chromatography. Resolution of the water-soluble vitamins--pyridoxin, riboflavin, niacinamide, vitamin B12, thiamin, ascorbic acid, niacin and folic acid--by high pressure liquid chromatography was examined on two bonded-phase columns, muBondapak C18 and muBondapak NH2. The effect on the retention times of individual vitamins and the separation of a multivitamin sample was determined using varying proportions of water/methanol as the eluting solvent and by addition of various salts, buffer solutions and PIC reagents to the water/methanol. Each vitamin was able to be eluted satisfactorily from muBondapak C18. It was found that seven vitamins could be resolved from a multivitamin mixture in a single analysis in several solvent systems with the total time for the analyses being always less than 40 min. With muBondapak NH2, all the vitamins except folic acid were eluted and six vitamins could be resolved from a mixture in a single analysis. The speed of analysis was greater with muBondapak NH2 with all compounds eluted in 15 min and the peaks were sharper. The order of elution was essentially the reverse of that obtained with muBondapak C18."}
{"id": "PMID:19496", "title": "Isolation of an obligately anaerobic Streptococcus pneumoniae from blood culture.", "content": "An obligately anaerobic strain of Streptococcus pneumoniae was isolated from blood culture in a 14-month-old child with an upper respiratory tract infection.", "contents": "Isolation of an obligately anaerobic Streptococcus pneumoniae from blood culture. An obligately anaerobic strain of Streptococcus pneumoniae was isolated from blood culture in a 14-month-old child with an upper respiratory tract infection."}
{"id": "PMID:19497", "title": "Bicarbonate transport by rabbit cortical collecting tubules. Effect of acid and alkali loads in vivo on transport in vitro.", "content": "Rabbit cortical collecting tubules were perfused in vitro to investigate the control of bicarbonate transport. Bicarbonate was measured by microcalorimetry as total CO2. The perfusate and bath were identical solutions containing 25 mM bicarbonate at pH 7.4. The mean pH of the urine in the bladders of untreated rabbits at the time they were killed was 7.4. Their individual tubules, studied in vitro, either absorbed or secreted bicarbonate, and, combining the results, there was on the average no significant net transport. When the rabbits were treated with NH4Cl the day before the experiment, their urine was acidic and their tubules studied in vitro absorbed bicarbonate (i.e., there was net lumen-to-bath transport). In contrast, when the rabbits were treated with NaHCO3, their urine was significantly more alkaline, and their tubules studied in vitro generally secreted bicarbonate (i.e., net bath-to-lumen transport). Thus, the direction of bicarbonate transport by cortical collecting tubules studied under standard conditions in vitro correlated with the urine pH and was determined by the preceding treatment of the animals in vivo with acidifying or alkalinizing salts. These results demonstrate a previously unrecognized mechanism which contributes to the control of urinary bicarbonate excretion.", "contents": "Bicarbonate transport by rabbit cortical collecting tubules. Effect of acid and alkali loads in vivo on transport in vitro. Rabbit cortical collecting tubules were perfused in vitro to investigate the control of bicarbonate transport. Bicarbonate was measured by microcalorimetry as total CO2. The perfusate and bath were identical solutions containing 25 mM bicarbonate at pH 7.4. The mean pH of the urine in the bladders of untreated rabbits at the time they were killed was 7.4. Their individual tubules, studied in vitro, either absorbed or secreted bicarbonate, and, combining the results, there was on the average no significant net transport. When the rabbits were treated with NH4Cl the day before the experiment, their urine was acidic and their tubules studied in vitro absorbed bicarbonate (i.e., there was net lumen-to-bath transport). In contrast, when the rabbits were treated with NaHCO3, their urine was significantly more alkaline, and their tubules studied in vitro generally secreted bicarbonate (i.e., net bath-to-lumen transport). Thus, the direction of bicarbonate transport by cortical collecting tubules studied under standard conditions in vitro correlated with the urine pH and was determined by the preceding treatment of the animals in vivo with acidifying or alkalinizing salts. These results demonstrate a previously unrecognized mechanism which contributes to the control of urinary bicarbonate excretion."}
{"id": "PMID:19498", "title": "Relationship between phosphaluria and acute hypercapnia in the rat.", "content": "Standard clearance studies were performed in mechanically ventilated intact and acutely thyroparathyroidectomized (TPTX) rats to document and characterize the effect of hypercapnia (HC) on urinary phosphorus excretion (U(P)V). HC as compared to normocapnia (NC) was associated with an increase in U(P)V in intact (62.5 vs. 7.93 mug/min) and TPTX (30.5 vs. 0.59 mug/min) rats, an increase in filtered load of phosphorus in intact (218 vs. 191 mug/min) and TPTX (243 vs. 146 mug/min) rats, an increase in blood bicarbonate concentration in intact (27.8 vs. 26.0 meq/liter) and TPTX (24.5 vs. 22.3 meq/liter) animals, and a decrease in blood pH in intact (7.15 vs. 7.42) and TPTX (7.07 vs. 7.39) rats. Additional TPTX rats with NC and HC were studied during phosphorus infusion at a comparable filtered load of phosphorus (NC = 307 mug/min and HC = 328 mug/min). U(P)V was 18.5 mug/min in NC and 85.2 mug/min in HC animals. Intact NC animals infused with NaHCO(3) achieved a blood bicarbonate of 45.9 meq/liter compared to 26.0 meq/liter in intact NC NaCl-infused rats. U(P)V was 10.0 mug/min in the NaHCO(3) and 7.93 mug/min in NaCl-infused animals. In intact HC animals infused with NaHCO(3), blood pH was 7.36 compared to 7.42 in NC intact NaCl-infused animals. U(P)V was 83.2 mug/min in the HC bicarbonate-infused and 7.93 mug/min in the NC NaCl-infused rats. These experiments demonstrate that elevated blood carbon dioxide tension per se increases U(P)V. Increases in filtered load of phosphorus and blood bicarbonate which are associated with HC contribute to the phosphaturia as does parathyroid hormone. The phosphaturia is not dependent upon reduction of extracellular pH.", "contents": "Relationship between phosphaluria and acute hypercapnia in the rat. Standard clearance studies were performed in mechanically ventilated intact and acutely thyroparathyroidectomized (TPTX) rats to document and characterize the effect of hypercapnia (HC) on urinary phosphorus excretion (U(P)V). HC as compared to normocapnia (NC) was associated with an increase in U(P)V in intact (62.5 vs. 7.93 mug/min) and TPTX (30.5 vs. 0.59 mug/min) rats, an increase in filtered load of phosphorus in intact (218 vs. 191 mug/min) and TPTX (243 vs. 146 mug/min) rats, an increase in blood bicarbonate concentration in intact (27.8 vs. 26.0 meq/liter) and TPTX (24.5 vs. 22.3 meq/liter) animals, and a decrease in blood pH in intact (7.15 vs. 7.42) and TPTX (7.07 vs. 7.39) rats. Additional TPTX rats with NC and HC were studied during phosphorus infusion at a comparable filtered load of phosphorus (NC = 307 mug/min and HC = 328 mug/min). U(P)V was 18.5 mug/min in NC and 85.2 mug/min in HC animals. Intact NC animals infused with NaHCO(3) achieved a blood bicarbonate of 45.9 meq/liter compared to 26.0 meq/liter in intact NC NaCl-infused rats. U(P)V was 10.0 mug/min in the NaHCO(3) and 7.93 mug/min in NaCl-infused animals. In intact HC animals infused with NaHCO(3), blood pH was 7.36 compared to 7.42 in NC intact NaCl-infused animals. U(P)V was 83.2 mug/min in the HC bicarbonate-infused and 7.93 mug/min in the NC NaCl-infused rats. These experiments demonstrate that elevated blood carbon dioxide tension per se increases U(P)V. Increases in filtered load of phosphorus and blood bicarbonate which are associated with HC contribute to the phosphaturia as does parathyroid hormone. The phosphaturia is not dependent upon reduction of extracellular pH."}
{"id": "PMID:19499", "title": "Interactions among heparin, cold-insoluble globulin, and fibrinogen in formation of the heparin-precipitable fraction of plasma.", "content": "Fibrinogen and the cold-insoluble globulin of plasma (CIg) are the main protein components of the heparin-precipitable fraction of normal plasma. The interactions among these proteins and heparin were examined. Heparin formed a cold-precipitable complex with purified CIg or with mixtures of CIg and fibrinogen but not with purified fibrinogen alone. Cryoprecipitation was augmented by addition of Ca(++) or by selection of optimal heparin levels; it was reduced or even abolished by raising the ionic strength or pH or both, or by raising the heparin concentration above that for maximum precipitation of CIg. Fibrinogen reduced the threshold for heparin-induced CIg cryoprecipitation and, by coprecipitating with heparin and CIg, increased the amount of precipitate that formed. In contrast to the heparin-precipitable fraction of normal plasma which contained both fibrinogen and CIg, that from a patient with congenital afibrinogenemia contained CIg but lacked fibrinogen. Normal plasma depleted of CIg by immunoabsorption failed to form a heparin-induced cryoprecipitate. Thus, CIg is essential for heparin-induced cryoprecipitation to occur. Fibrinogen, as assessed by chromatographic experiments with heparin-Sepharose columns, had a considerably lower binding affinity for heparin than did CIg, suggesting that it participates in precipitate formation mainly, if not entirely, by virtue of its affinity for CIg. The region of the fibrinogen molecule accounting for its precipitation with CIg appears to be localized in the carboxy-terminal segment of the Aalpha-chain; fibrinogen subfractions lacking this region failed to augment cryoprecipitation of heparin-CIg mixtures and, even though such species were present in normal plasma, they failed to coprecipitate in the heparin-induced complex.", "contents": "Interactions among heparin, cold-insoluble globulin, and fibrinogen in formation of the heparin-precipitable fraction of plasma. Fibrinogen and the cold-insoluble globulin of plasma (CIg) are the main protein components of the heparin-precipitable fraction of normal plasma. The interactions among these proteins and heparin were examined. Heparin formed a cold-precipitable complex with purified CIg or with mixtures of CIg and fibrinogen but not with purified fibrinogen alone. Cryoprecipitation was augmented by addition of Ca(++) or by selection of optimal heparin levels; it was reduced or even abolished by raising the ionic strength or pH or both, or by raising the heparin concentration above that for maximum precipitation of CIg. Fibrinogen reduced the threshold for heparin-induced CIg cryoprecipitation and, by coprecipitating with heparin and CIg, increased the amount of precipitate that formed. In contrast to the heparin-precipitable fraction of normal plasma which contained both fibrinogen and CIg, that from a patient with congenital afibrinogenemia contained CIg but lacked fibrinogen. Normal plasma depleted of CIg by immunoabsorption failed to form a heparin-induced cryoprecipitate. Thus, CIg is essential for heparin-induced cryoprecipitation to occur. Fibrinogen, as assessed by chromatographic experiments with heparin-Sepharose columns, had a considerably lower binding affinity for heparin than did CIg, suggesting that it participates in precipitate formation mainly, if not entirely, by virtue of its affinity for CIg. The region of the fibrinogen molecule accounting for its precipitation with CIg appears to be localized in the carboxy-terminal segment of the Aalpha-chain; fibrinogen subfractions lacking this region failed to augment cryoprecipitation of heparin-CIg mixtures and, even though such species were present in normal plasma, they failed to coprecipitate in the heparin-induced complex."}
{"id": "PMID:19500", "title": "Effects of hypermetabolism on ventilation and chemosensitivity.", "content": "Muscular exercise is associated with hypermetabolism and increased hypoxic ventilatory response (HVR). In order to dissociate mechanical and metabolic factors, the effect of hypermetabolism on hypoxic ventilatory response was evaluated at rest. Carbohydrate and protein feeding increases metabolic rate, and their effects on chemosensitivity, ventilation, and blood pH were evaluated in six normal subjects 2 h and 3 h after calorically equal test meals (1,000 cal). After carbohydrate, base-line oxygen consumption (Vo(2)) increased from 237+/-11.3 ml/min (SEM) to 302+/-19.4 (P < 0.001) and 303+/-18.5 (P < 0.001) at 2 h and 3 h, respectively. Hypoxic ventilatory response, measured as shape parameter A, increased from a control of 144+/-11.8 to 330+/-61.0 (P < 0.01) at 2 h and 286+/-57.0 (P < 0.05) at 3 h. These changes were associated with a mild metabolic acidosis as pH decreased from a control of 7.402+/-0.004 to 7.371+/-0.009 (P < 0.005) at 2 h and 7.377+/-0.008 (P < 0.005) at 3 h. After protein, Vo(2) increased from 241+/-6.7 to 265+/-6.2 (P < 0.02) and 270+/-5.4 (P < 0.001), an overall increase less than that which occurred after carbohydrate (P < 0.01). Hypoxic ventilatory response increased from 105+/-14.5 to 198+/-24.3 (P < 0.02) at 2 h and 219+/-17.3 (P < 0.01) at 3 h, which was not different from the increase with carbohydrate. After protein, no acidosis occurred. Thus, after protein, HVR increased despite the absence of a systemic acidosis. We conclude that both carbohydrate and protein feedings are associated with resting hypermetabolism and increased HVR compared with the fasting state. For both meals, increased metabolic rate was correlated with increased hypoxic response.", "contents": "Effects of hypermetabolism on ventilation and chemosensitivity. Muscular exercise is associated with hypermetabolism and increased hypoxic ventilatory response (HVR). In order to dissociate mechanical and metabolic factors, the effect of hypermetabolism on hypoxic ventilatory response was evaluated at rest. Carbohydrate and protein feeding increases metabolic rate, and their effects on chemosensitivity, ventilation, and blood pH were evaluated in six normal subjects 2 h and 3 h after calorically equal test meals (1,000 cal). After carbohydrate, base-line oxygen consumption (Vo(2)) increased from 237+/-11.3 ml/min (SEM) to 302+/-19.4 (P < 0.001) and 303+/-18.5 (P < 0.001) at 2 h and 3 h, respectively. Hypoxic ventilatory response, measured as shape parameter A, increased from a control of 144+/-11.8 to 330+/-61.0 (P < 0.01) at 2 h and 286+/-57.0 (P < 0.05) at 3 h. These changes were associated with a mild metabolic acidosis as pH decreased from a control of 7.402+/-0.004 to 7.371+/-0.009 (P < 0.005) at 2 h and 7.377+/-0.008 (P < 0.005) at 3 h. After protein, Vo(2) increased from 241+/-6.7 to 265+/-6.2 (P < 0.02) and 270+/-5.4 (P < 0.001), an overall increase less than that which occurred after carbohydrate (P < 0.01). Hypoxic ventilatory response increased from 105+/-14.5 to 198+/-24.3 (P < 0.02) at 2 h and 219+/-17.3 (P < 0.01) at 3 h, which was not different from the increase with carbohydrate. After protein, no acidosis occurred. Thus, after protein, HVR increased despite the absence of a systemic acidosis. We conclude that both carbohydrate and protein feedings are associated with resting hypermetabolism and increased HVR compared with the fasting state. For both meals, increased metabolic rate was correlated with increased hypoxic response."}
{"id": "PMID:19501", "title": "The influence of thyroid hormones on in vitro erythropoiesis. Mediation by a receptor with beta adrenergic properties.", "content": "The erythropoietic effect of various thyroid hormones has been studied using erythroid colony formation by canine marrow cells. Although erythropoietin was required for colony growth, physiologic levels of thyroid hormones significantly enhanced colony numbers. The order of potency of the thyroid compounds in their in vitro erythropoietic effect parallels their known calorigenic potency in vivo, suggesting that the in vitro effect is physiologically relevant. A series of studies linked the mechanism of thyroid action to adrenergic receptors on responsive cells. Propranolol, a global beta-blocker, inhibited thyroid hormone-responsive erythroid colonies. When adrenergic antagonists having different blocking characteristics were added to culture, the thyroid hormone effect was blocked by those compounds having beta(2)-subspecificity. Velocity sedimentation analysis showed that the peak of colony-forming cells which respond to thyroid hormone and the adrenergic agonist, isoproterenol, sedimented at an identical rate (7.54 mm/h), which is slower than the major peak of colony-forming cells responding to erythropoietin alone (8.62 mm/h). These results demonstrate thyroid hormonal enhancement of in vitro erythroid colony growth which appears mediated by a receptor with beta(2)-adrenergic properties. The data suggest that changes in hormone-target cell interaction may occur during states of abnormal thyroid function.", "contents": "The influence of thyroid hormones on in vitro erythropoiesis. Mediation by a receptor with beta adrenergic properties. The erythropoietic effect of various thyroid hormones has been studied using erythroid colony formation by canine marrow cells. Although erythropoietin was required for colony growth, physiologic levels of thyroid hormones significantly enhanced colony numbers. The order of potency of the thyroid compounds in their in vitro erythropoietic effect parallels their known calorigenic potency in vivo, suggesting that the in vitro effect is physiologically relevant. A series of studies linked the mechanism of thyroid action to adrenergic receptors on responsive cells. Propranolol, a global beta-blocker, inhibited thyroid hormone-responsive erythroid colonies. When adrenergic antagonists having different blocking characteristics were added to culture, the thyroid hormone effect was blocked by those compounds having beta(2)-subspecificity. Velocity sedimentation analysis showed that the peak of colony-forming cells which respond to thyroid hormone and the adrenergic agonist, isoproterenol, sedimented at an identical rate (7.54 mm/h), which is slower than the major peak of colony-forming cells responding to erythropoietin alone (8.62 mm/h). These results demonstrate thyroid hormonal enhancement of in vitro erythroid colony growth which appears mediated by a receptor with beta(2)-adrenergic properties. The data suggest that changes in hormone-target cell interaction may occur during states of abnormal thyroid function."}
{"id": "PMID:19502", "title": "Judgment of emotion among chronic schizophrenics.", "content": "This study investigated accuracy of judgment as to posed facial expressions and nonverbal scenes of various emotions. Ss were 16 male and 16 female chronic schizophrenics and a normal control group of equal size and sex composition. The results revealed that normal Ss were significantly more accurate than schizophrenics in identifying emotions from both posed photographs of the face and nonverbal videotape scenes. S sex was not found to affect differentially the schizophrenic or normal Ss' response accuracy to both the photographs and videotapes. Further, it was observed that both groups' accuracy improved when given multiple-choice alternatives to select from as contrasted to their open-ended free responses; this was especially true for the schizophrenic group. Teaching patients to identify and practice expressing discrete emotions was suggested.", "contents": "Judgment of emotion among chronic schizophrenics. This study investigated accuracy of judgment as to posed facial expressions and nonverbal scenes of various emotions. Ss were 16 male and 16 female chronic schizophrenics and a normal control group of equal size and sex composition. The results revealed that normal Ss were significantly more accurate than schizophrenics in identifying emotions from both posed photographs of the face and nonverbal videotape scenes. S sex was not found to affect differentially the schizophrenic or normal Ss' response accuracy to both the photographs and videotapes. Further, it was observed that both groups' accuracy improved when given multiple-choice alternatives to select from as contrasted to their open-ended free responses; this was especially true for the schizophrenic group. Teaching patients to identify and practice expressing discrete emotions was suggested."}
{"id": "PMID:19503", "title": "The Brief Outpatient Psychopathology Scale (BOPS).", "content": "The pertinence of a rating scale capable of characterizing presenting psychopathology and measuring degrees of change for psychoneurotic patients treated in an outpatient setting is described. Data for 328 patients who represent 1191 rating profiles were used to develop the factor structure for the New Physician's Rating List, a rating scale completed by health professionals after Patient interviews. Findings were used to develop the new Brief Outpatient Psychopathology Scale. A proposed factor structure is discussed. The structures of both scales include an Anxiety Syndrome composed of Anxiety and Psychomotor Activation Factors. The scales also include Depression and Somatization factors.", "contents": "The Brief Outpatient Psychopathology Scale (BOPS). The pertinence of a rating scale capable of characterizing presenting psychopathology and measuring degrees of change for psychoneurotic patients treated in an outpatient setting is described. Data for 328 patients who represent 1191 rating profiles were used to develop the factor structure for the New Physician's Rating List, a rating scale completed by health professionals after Patient interviews. Findings were used to develop the new Brief Outpatient Psychopathology Scale. A proposed factor structure is discussed. The structures of both scales include an Anxiety Syndrome composed of Anxiety and Psychomotor Activation Factors. The scales also include Depression and Somatization factors."}
{"id": "PMID:19504", "title": "Patients' expectancies and improvement in treatment: the shape of the link.", "content": "It has been hypothesized (a) that patients' expectancies for therapeutic gain are linked to the clinical improvement that the patients realize in treatment; and (b) that patients' expectancies may play a causative role in such improvement. The first hypothesis has received empirical support, but the second has not. This study tested the causativeinterpretation of patients' expectancies and a second interpretation, which states that patients' expectancies predict, but do not cause clinical improvement. The shape of thelink between expectancy and improvement for hospitalized schizophrenics was explored. Based on motivation research it was reasoned that a curvilinear relationship between expectancy and improvement would support a causative interpretation and that a linear relationship would support a predictive interpretation of the nature of expectancy. Multiple regression analyses found a linear relationship between expectancies and objective measures of improvement for the patients, but no evidence of a curvilinear relationship between these measures. The results were interpreted as supporting a predictive interpretation of the expectancies of hospitalized schizophrenic patients.", "contents": "Patients' expectancies and improvement in treatment: the shape of the link. It has been hypothesized (a) that patients' expectancies for therapeutic gain are linked to the clinical improvement that the patients realize in treatment; and (b) that patients' expectancies may play a causative role in such improvement. The first hypothesis has received empirical support, but the second has not. This study tested the causativeinterpretation of patients' expectancies and a second interpretation, which states that patients' expectancies predict, but do not cause clinical improvement. The shape of thelink between expectancy and improvement for hospitalized schizophrenics was explored. Based on motivation research it was reasoned that a curvilinear relationship between expectancy and improvement would support a causative interpretation and that a linear relationship would support a predictive interpretation of the nature of expectancy. Multiple regression analyses found a linear relationship between expectancies and objective measures of improvement for the patients, but no evidence of a curvilinear relationship between these measures. The results were interpreted as supporting a predictive interpretation of the expectancies of hospitalized schizophrenic patients."}
{"id": "PMID:19505", "title": "Comparison of bumetanide and hydrochlorothiazide on renal potassium and hydrogen ion excretion.", "content": "The purpose of this study was to compare the renal electrolyte excretion pattern of bumetanide with that of hydrochlorothiazide in dogs anesthetized with pentobarbital. In bumetanide-treated animals, mean sodium excretion rose to 12 per cent of the filtered load, while hydrochlorothiazide increased sodium excretion to 4 per cent of the filtered load. After bumetanide, urine pH fell from 6.1 to 5.1 and net hydrogenion excretion increased significantly. After hydrochlorothiazide, urinary pH went from 6.4 to 7.4, and there was no change in net hydrogen ion excretion. Potassium excretion rose to 106+/-22 muEq/min with bumetanide and to 99+/-17 muEq/min with hydrochlorothiazide. These changes in electrolyte excretion occurred despite lack of changes in arterial blood gases, arterial blood pressure, and glomerular filtration rate. In addition, bumetanide did not exert an inhibitory effect on potassium excretion under conditions of potassium loading. It is concluded that bumetanide produces a higher urinary Na+:K+ ratio with a lower pH than hydrochlorothiazide and that renal potassium ion excretion in response to sulfamoyl diuretics is not solely dependent on the rate of sodium excretion.", "contents": "Comparison of bumetanide and hydrochlorothiazide on renal potassium and hydrogen ion excretion. The purpose of this study was to compare the renal electrolyte excretion pattern of bumetanide with that of hydrochlorothiazide in dogs anesthetized with pentobarbital. In bumetanide-treated animals, mean sodium excretion rose to 12 per cent of the filtered load, while hydrochlorothiazide increased sodium excretion to 4 per cent of the filtered load. After bumetanide, urine pH fell from 6.1 to 5.1 and net hydrogenion excretion increased significantly. After hydrochlorothiazide, urinary pH went from 6.4 to 7.4, and there was no change in net hydrogen ion excretion. Potassium excretion rose to 106+/-22 muEq/min with bumetanide and to 99+/-17 muEq/min with hydrochlorothiazide. These changes in electrolyte excretion occurred despite lack of changes in arterial blood gases, arterial blood pressure, and glomerular filtration rate. In addition, bumetanide did not exert an inhibitory effect on potassium excretion under conditions of potassium loading. It is concluded that bumetanide produces a higher urinary Na+:K+ ratio with a lower pH than hydrochlorothiazide and that renal potassium ion excretion in response to sulfamoyl diuretics is not solely dependent on the rate of sodium excretion."}
{"id": "PMID:19507", "title": "Twin crossover relative potency analgesic assays in man. II. Morphine vs. 8-methoxycyclazocine.", "content": "Using the twin crossover, balanced incomplete block design described in the previous paper, a double-blind determination of the relative analgesic potency of graded intramuscular doses of Win 20,836 (8-methoxycyclazocine) and morphine was carried out in patients with postoperative pain. Although no preliminary data at all on the human analgesic activity of Win 20,836 were available, the sequential decision-making process designed to choose the doses of the test medication most closely equianalgesic with the standard functioned efficiently to establish doses of Win 20,836 that had analgesic activity. Unfortunately, the occurrence of psychotomimetic side effects prevented the administration of doses of Win 20,836 equieffective with the morphine standard, and this necessitated substantal extrapolation of the dose-response curve of the test drug to arrive at a relative potency estimate. However, our relative potency estimate, which indicated that Win 20,836 is three to six times as potent as morphine, was dependable enough to predict with reasonable certainty that doses of Win 20,836 equieffective to the usual doses of morphine would produce an unacceptable level of psychotomimetic side effects. Clinical investigation of the drug was therefore terminated.", "contents": "Twin crossover relative potency analgesic assays in man. II. Morphine vs. 8-methoxycyclazocine. Using the twin crossover, balanced incomplete block design described in the previous paper, a double-blind determination of the relative analgesic potency of graded intramuscular doses of Win 20,836 (8-methoxycyclazocine) and morphine was carried out in patients with postoperative pain. Although no preliminary data at all on the human analgesic activity of Win 20,836 were available, the sequential decision-making process designed to choose the doses of the test medication most closely equianalgesic with the standard functioned efficiently to establish doses of Win 20,836 that had analgesic activity. Unfortunately, the occurrence of psychotomimetic side effects prevented the administration of doses of Win 20,836 equieffective with the morphine standard, and this necessitated substantal extrapolation of the dose-response curve of the test drug to arrive at a relative potency estimate. However, our relative potency estimate, which indicated that Win 20,836 is three to six times as potent as morphine, was dependable enough to predict with reasonable certainty that doses of Win 20,836 equieffective to the usual doses of morphine would produce an unacceptable level of psychotomimetic side effects. Clinical investigation of the drug was therefore terminated."}
{"id": "PMID:19511", "title": "Reactivity and aggression in the rat: induction by alpha-adrenergic blocking agents injected ventral to anterior septum but not into lateral septum.", "content": "Intracranial injections were made bilaterally through permanently implanted cannulas ending in the lateral septum or in the region ventral to the anterior septum. The rats were first screened with injections of a local anesthetic, lidocaine, which blocks both synaptic and axonal conduction. Those animals that showed an increase in reactivity and aggression were then injected with a synaptic transmitter blocking agent. The results showed that transmitter blocking agents reproduced the effect of the local anesthetic only in the region ventral to the anterior septum and that alpha-adrenergic (phentolamine, tolazoline), but not beta-adrenergic (propranolol, hydralazine), cholinergic (atropine, hyocine), or dopaminergic (haloperidol) blocking agents were effective. These results suggest that synapses in the forebrain system controlling reactivity and aggression are alpha-asrenergic and are located in the region ventral to the anterior septum just lateral to the diagonal band of Broca. The septum itself may be involved only to the extent that it is traversed by fibers of passage.", "contents": "Reactivity and aggression in the rat: induction by alpha-adrenergic blocking agents injected ventral to anterior septum but not into lateral septum. Intracranial injections were made bilaterally through permanently implanted cannulas ending in the lateral septum or in the region ventral to the anterior septum. The rats were first screened with injections of a local anesthetic, lidocaine, which blocks both synaptic and axonal conduction. Those animals that showed an increase in reactivity and aggression were then injected with a synaptic transmitter blocking agent. The results showed that transmitter blocking agents reproduced the effect of the local anesthetic only in the region ventral to the anterior septum and that alpha-adrenergic (phentolamine, tolazoline), but not beta-adrenergic (propranolol, hydralazine), cholinergic (atropine, hyocine), or dopaminergic (haloperidol) blocking agents were effective. These results suggest that synapses in the forebrain system controlling reactivity and aggression are alpha-asrenergic and are located in the region ventral to the anterior septum just lateral to the diagonal band of Broca. The septum itself may be involved only to the extent that it is traversed by fibers of passage."}
{"id": "PMID:19508", "title": "Clinical pharmacokinetics of lorazepam. III. Intravenous injection. Preliminary results.", "content": "Four healthy male volunteers received 5 mg lorazepam as a single intravenous injection. Concentrations of lorazepam and its glucuronide metabolite were determined in multiple venous blood samples drawn during the 48 hours after dosing and in all urine collected during 96 hours after the dose. Mean pharmacokinetic parameters for lorazepam were: apparent elimination half-life, 13.2 hours; volume of distribution, 0.84 liter/kg; total clearance, 55.3 ml/min. Lorazepam glucuronide, the major metabolic product of lorazepam, promptly appeared in blood, reached peak levels within 6 hours of the dose, then declined in parallel with the parent compound. A mean of 69 per cent of the dose was recovered in urine as lorazepam glucuronide.", "contents": "Clinical pharmacokinetics of lorazepam. III. Intravenous injection. Preliminary results. Four healthy male volunteers received 5 mg lorazepam as a single intravenous injection. Concentrations of lorazepam and its glucuronide metabolite were determined in multiple venous blood samples drawn during the 48 hours after dosing and in all urine collected during 96 hours after the dose. Mean pharmacokinetic parameters for lorazepam were: apparent elimination half-life, 13.2 hours; volume of distribution, 0.84 liter/kg; total clearance, 55.3 ml/min. Lorazepam glucuronide, the major metabolic product of lorazepam, promptly appeared in blood, reached peak levels within 6 hours of the dose, then declined in parallel with the parent compound. A mean of 69 per cent of the dose was recovered in urine as lorazepam glucuronide."}
{"id": "PMID:19506", "title": "Twin crossover relative potency analgesic assays in man. I. Morphine vs. morphine.", "content": "Although the four-point relative potency assay using crossover design has proven a powerful technique for the clinical evaluation of analgesics in patients with chronic pain, excessive dropouts have made this design impractical in postoperative pain. In a relative potency assay comparing single graded intramuscular doses of morphine standard and morphine test in postoperative patients, we have managed to circumvent this difficulty while preserving many of the advantages of a complete crossover by using the \"twin-crossover\" balanced incomplete block design, which requires that each subject receive only two of the four possible treatments. The \"twin crossover\" design, coupled with a sequential decision-making process that expedites choosing the doses of the test medication which are most closely equianalgesic with the standard, yielded excellent analgesic assay sensitivity and made efficient use of our population of postoperative patients.", "contents": "Twin crossover relative potency analgesic assays in man. I. Morphine vs. morphine. Although the four-point relative potency assay using crossover design has proven a powerful technique for the clinical evaluation of analgesics in patients with chronic pain, excessive dropouts have made this design impractical in postoperative pain. In a relative potency assay comparing single graded intramuscular doses of morphine standard and morphine test in postoperative patients, we have managed to circumvent this difficulty while preserving many of the advantages of a complete crossover by using the \"twin-crossover\" balanced incomplete block design, which requires that each subject receive only two of the four possible treatments. The \"twin crossover\" design, coupled with a sequential decision-making process that expedites choosing the doses of the test medication which are most closely equianalgesic with the standard, yielded excellent analgesic assay sensitivity and made efficient use of our population of postoperative patients."}
{"id": "PMID:19510", "title": "Evaluation of butaclamol in chronic schizophrenic patients.", "content": "In a double-blind, placebo-controlled study, an attempt was made to evaluate butaclamol in chronic schizophrenic patients using chlorpromazine (CPZ) as the standard comparative drug. With doses up to 50 mg/day, butaclamol was shown to have significant antipsychotic activity comparable to CPZ but with a much higher incidence of extrapyramidal signs. A more reasonable maintenance dose may be in the range of 5 to 20 mg/day. Rebound insomnia was noted again with butaclamol, which warrants further study.", "contents": "Evaluation of butaclamol in chronic schizophrenic patients. In a double-blind, placebo-controlled study, an attempt was made to evaluate butaclamol in chronic schizophrenic patients using chlorpromazine (CPZ) as the standard comparative drug. With doses up to 50 mg/day, butaclamol was shown to have significant antipsychotic activity comparable to CPZ but with a much higher incidence of extrapyramidal signs. A more reasonable maintenance dose may be in the range of 5 to 20 mg/day. Rebound insomnia was noted again with butaclamol, which warrants further study."}
{"id": "PMID:19514", "title": "Metabolic and cardiovascular effects of carbuterol and metaproterenol.", "content": "Metabolic and cardiovascular responses to selective beta-adrenergic bronchodilators, carbuterol and metaproterenol, were studied during an asymptomatic period in 8 male subjects with bronchial asthma diagnosed as mile to moderate. On separate days each individual received either placebo, carbuterol 2 mg, carbuterol 4 mg, or metaproterenol 20 mg orally in a double-blind fashion. Subsequently, metabolic and cardiovascular responses were measured periodically for 5 hr. Carbuterol 2 mg was indistinguishable from placebo except for small elevations of glucose at 3 and 4 hr. Carbuterol 4 mg produced significant increases in glucose, insulin, lactate, and free fatty acids as well as in pulse rate and arterial pulse pressure. Metaproterenol produced increases only in plasma glucose and insulin. The majority of patients reported drug-related side effects which were all mild, after taking either carbuterol 4 mg or metaproterenol 20 mg. Fewer subjective side effects were noted with carbuterol 2 mg. These findings indicate that a 2-mg dose of carbuterol can be administered to typical asthmatic subjects without significant subjective or objective side effects. The larger dose (4 mg) may be accompanied by a greater frequency of side effects.", "contents": "Metabolic and cardiovascular effects of carbuterol and metaproterenol. Metabolic and cardiovascular responses to selective beta-adrenergic bronchodilators, carbuterol and metaproterenol, were studied during an asymptomatic period in 8 male subjects with bronchial asthma diagnosed as mile to moderate. On separate days each individual received either placebo, carbuterol 2 mg, carbuterol 4 mg, or metaproterenol 20 mg orally in a double-blind fashion. Subsequently, metabolic and cardiovascular responses were measured periodically for 5 hr. Carbuterol 2 mg was indistinguishable from placebo except for small elevations of glucose at 3 and 4 hr. Carbuterol 4 mg produced significant increases in glucose, insulin, lactate, and free fatty acids as well as in pulse rate and arterial pulse pressure. Metaproterenol produced increases only in plasma glucose and insulin. The majority of patients reported drug-related side effects which were all mild, after taking either carbuterol 4 mg or metaproterenol 20 mg. Fewer subjective side effects were noted with carbuterol 2 mg. These findings indicate that a 2-mg dose of carbuterol can be administered to typical asthmatic subjects without significant subjective or objective side effects. The larger dose (4 mg) may be accompanied by a greater frequency of side effects."}
{"id": "PMID:19509", "title": "Clinical pharmacokinetics of lorazepam. IV. Long-term oral administration.", "content": "Fifteen healthy male volunteers received long-term daily treatment with oral lorazepam at doses as high as 10 mg per day for a period of 26 weeks. Steady-state plasma concentrations of lorazepam and its glucuronide metabolite were measured in all subjects at least every two weeks. At daily doses of 6 mg per day, the mean steady-state lorazepam level was 88 ng/ml and that of lorazepam glucuronide was 170 ng/ml. Mean levels among seven subjects who received 10 mg per day were 164 and 266 ng/ml, respectively. Lorazepam concentrations fluctuated from week to week despite constant dosage, but there was no evidence of systematic variation. Mean steady-state lorazepam levels were highly correlated with daily dose in mg/kg, but were not related to age. Lorazepam was not detected in any plasma samples drawn one week after discontinuation of treatment.", "contents": "Clinical pharmacokinetics of lorazepam. IV. Long-term oral administration. Fifteen healthy male volunteers received long-term daily treatment with oral lorazepam at doses as high as 10 mg per day for a period of 26 weeks. Steady-state plasma concentrations of lorazepam and its glucuronide metabolite were measured in all subjects at least every two weeks. At daily doses of 6 mg per day, the mean steady-state lorazepam level was 88 ng/ml and that of lorazepam glucuronide was 170 ng/ml. Mean levels among seven subjects who received 10 mg per day were 164 and 266 ng/ml, respectively. Lorazepam concentrations fluctuated from week to week despite constant dosage, but there was no evidence of systematic variation. Mean steady-state lorazepam levels were highly correlated with daily dose in mg/kg, but were not related to age. Lorazepam was not detected in any plasma samples drawn one week after discontinuation of treatment."}
{"id": "PMID:19529", "title": "The dispersal of cells from human gynecologic specimens: chemical agents.", "content": "An investigation of nonenzymatic chemical solutions for the dispersal of gynecologic cells in suspension was undertaken using known general information on the composition of cell surfaces and cell adhesive properties. Studies on human cells cultured in vitro showed that thiol reducing agents release microextension-mediated contacts. Dispersing solutions containing lithium diiodosalicylate separated cells, presumably by extracting glycoproteins. Solutions without this agent but containing tetramethylurea and mixed sugars similar to those found on the cell surface separated cells by interacting with hydrogen bonds and other noncovalent polysaccharide interactions thought to hold cells together. Solutions containing ethylenediaminetetraacetate, dithiothreitol, tetramethylurea, mixed sugars, mixed amines and inorganic ions are suggested as mildly-acting dispersal solutions on the basis of evaluationtions by phase contrast microscopy, Papanicolaou staining and particle volume analysis.", "contents": "The dispersal of cells from human gynecologic specimens: chemical agents. An investigation of nonenzymatic chemical solutions for the dispersal of gynecologic cells in suspension was undertaken using known general information on the composition of cell surfaces and cell adhesive properties. Studies on human cells cultured in vitro showed that thiol reducing agents release microextension-mediated contacts. Dispersing solutions containing lithium diiodosalicylate separated cells, presumably by extracting glycoproteins. Solutions without this agent but containing tetramethylurea and mixed sugars similar to those found on the cell surface separated cells by interacting with hydrogen bonds and other noncovalent polysaccharide interactions thought to hold cells together. Solutions containing ethylenediaminetetraacetate, dithiothreitol, tetramethylurea, mixed sugars, mixed amines and inorganic ions are suggested as mildly-acting dispersal solutions on the basis of evaluationtions by phase contrast microscopy, Papanicolaou staining and particle volume analysis."}
{"id": "PMID:19530", "title": "The antibody response to the T1699 murine adenocarcinoma: antibody class and subclass heterogeneity detected in serum and in situ.", "content": "We have used indirect immunofluorescence to study antibody responses directed against membrane antigens expressed on in vitro and in vivo T1699 mammary adenocarcinoma cells. IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM antibodies were present in the serum of DBA/2 mice bearing T1699 tumors; IgG2a and IgG2b antibodies were readily detected on the cells in situ. Lesser amounts of the other classes and subclasses could be detected by indirect immunofluorescence measurements on in vivo tumor cells and with low pH eluates of in vivo cells tested on the in vitro line of T1699. The antigenic determinants on in situ tumor cells are not saturated with antibody as these cells demonstrated enhanced fluorescence of all immunoglobulin classes and subclasses when treated with autologous serum. Experiments with thymus-depleted mice indicated that immunoglobulin production was strongly dependent on thymus-derived cells for all immunoglobulin classes and subclasses except IgG2b. Our studies suggest that IgG2a may be active in the macrophage-mediated cytotoxic reaction and IgG2b in the immediate hypersensitivity reaction to T1699 cells. These results provide further evidence for an active role of tumor-specific antibody in the host defense to the T1699 adenocarcinoma in situ.", "contents": "The antibody response to the T1699 murine adenocarcinoma: antibody class and subclass heterogeneity detected in serum and in situ. We have used indirect immunofluorescence to study antibody responses directed against membrane antigens expressed on in vitro and in vivo T1699 mammary adenocarcinoma cells. IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM antibodies were present in the serum of DBA/2 mice bearing T1699 tumors; IgG2a and IgG2b antibodies were readily detected on the cells in situ. Lesser amounts of the other classes and subclasses could be detected by indirect immunofluorescence measurements on in vivo tumor cells and with low pH eluates of in vivo cells tested on the in vitro line of T1699. The antigenic determinants on in situ tumor cells are not saturated with antibody as these cells demonstrated enhanced fluorescence of all immunoglobulin classes and subclasses when treated with autologous serum. Experiments with thymus-depleted mice indicated that immunoglobulin production was strongly dependent on thymus-derived cells for all immunoglobulin classes and subclasses except IgG2b. Our studies suggest that IgG2a may be active in the macrophage-mediated cytotoxic reaction and IgG2b in the immediate hypersensitivity reaction to T1699 cells. These results provide further evidence for an active role of tumor-specific antibody in the host defense to the T1699 adenocarcinoma in situ."}
{"id": "PMID:19532", "title": "Sensitivity of amplifier T cells involved in the antibody response to type III pneumococcal polysaccharide to anti-lymphocyte serum.", "content": "Amplifier T cells responsible for enhancement of the antibody response to type III pneumococcal polysaccharide have been shown to be resistant to the effects of antilymphocyte serum (ALS) given at the time of immunization, a treatment that eliminates suppressor T cell activity. The resistance of amplifier T cells to ALS can be attributed to the fact that their activity develops after that of suppressor T cells. ALS given 1 or 2 days after immunization does abrogate amplifier T cell activity, independent of the mode by which that activity is elicited. The data emphasize the importance of kinetic considerations in understanding the effects produced by immunologically active agents such as ALS.", "contents": "Sensitivity of amplifier T cells involved in the antibody response to type III pneumococcal polysaccharide to anti-lymphocyte serum. Amplifier T cells responsible for enhancement of the antibody response to type III pneumococcal polysaccharide have been shown to be resistant to the effects of antilymphocyte serum (ALS) given at the time of immunization, a treatment that eliminates suppressor T cell activity. The resistance of amplifier T cells to ALS can be attributed to the fact that their activity develops after that of suppressor T cells. ALS given 1 or 2 days after immunization does abrogate amplifier T cell activity, independent of the mode by which that activity is elicited. The data emphasize the importance of kinetic considerations in understanding the effects produced by immunologically active agents such as ALS."}
{"id": "PMID:19533", "title": "Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide. II. Ability of suppressor T cells to act on both B cells and amplified T cells to limit the magnitude of the antibody response.", "content": "When administered 2 days after immunization with 0.5 microgram Type III pneumococcal polysaccharide (SSS-III), the T lymphocyte mitogen concanavalin A (Con A) stimulates a 2.6-to 7-fold enhancement of the plaque-forming cells (PFC) response to SSS-III in vivo. This enhancement requires the presence of amplified T cells, which act by driving PFC or their precursors to extra rounds of proliferation. The extra proliferation that can be stimulated by Con A is not seen in the normal primary response to SSS-III; but treatment with anti-lymphocyte serum (ALS) to remove suppressor T cells will permit the additional proliferation to occur. This indicates that in the primary response to SSS-III, suppressor T cells act on amplifier T cells to limit the magnitude of the antibody response. Only suppression of B cells can account for the further suppression induced by Con A given at the time of immunization or by low-dose paralysis of the SSS-III response. The relatively late development of amplified activity compared to suppressor activity appears to account for the absence of amplifier activity after primary immunization with SSS-III. It is apparent that one can explain the regulatory effects observed during the development of an immune response to SSS-III only by considering both T cell- B cell and T cell- T cell interactions, together with the temporal relationships involved in those interactions.", "contents": "Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide. II. Ability of suppressor T cells to act on both B cells and amplified T cells to limit the magnitude of the antibody response. When administered 2 days after immunization with 0.5 microgram Type III pneumococcal polysaccharide (SSS-III), the T lymphocyte mitogen concanavalin A (Con A) stimulates a 2.6-to 7-fold enhancement of the plaque-forming cells (PFC) response to SSS-III in vivo. This enhancement requires the presence of amplified T cells, which act by driving PFC or their precursors to extra rounds of proliferation. The extra proliferation that can be stimulated by Con A is not seen in the normal primary response to SSS-III; but treatment with anti-lymphocyte serum (ALS) to remove suppressor T cells will permit the additional proliferation to occur. This indicates that in the primary response to SSS-III, suppressor T cells act on amplifier T cells to limit the magnitude of the antibody response. Only suppression of B cells can account for the further suppression induced by Con A given at the time of immunization or by low-dose paralysis of the SSS-III response. The relatively late development of amplified activity compared to suppressor activity appears to account for the absence of amplifier activity after primary immunization with SSS-III. It is apparent that one can explain the regulatory effects observed during the development of an immune response to SSS-III only by considering both T cell- B cell and T cell- T cell interactions, together with the temporal relationships involved in those interactions."}
{"id": "PMID:19535", "title": "The presence of immunoregulatory cells in chicken thymus: function in B and T cell responses.", "content": "The presence of immunoregulatory cells in chicken thymus was studied by using several different systems. Chickens injected with large numbers of syngeneic thymocytes were tested for their ability to produce antibody to heterologous red cells. Similar chickens were studied for their ability to reject allogeneic skin grafts. In separate studies, mixtures of thymocytes with spleen cells or with peripheral blood leukocytes were assayed for their ability to respond to PHA or to produce a graft-vs-host reaction in embryonic chicks. These studies indicated that immunoregulatory cells exist in chicken thymus, which displays both helper and suppressor activity. The suppressor cells were more prevalent or more easily detectable in young birds and in chickens with intact bursas. The helper function of thymocytes was seen to better advantage with cells derived from older animals and from bursectomized donors.", "contents": "The presence of immunoregulatory cells in chicken thymus: function in B and T cell responses. The presence of immunoregulatory cells in chicken thymus was studied by using several different systems. Chickens injected with large numbers of syngeneic thymocytes were tested for their ability to produce antibody to heterologous red cells. Similar chickens were studied for their ability to reject allogeneic skin grafts. In separate studies, mixtures of thymocytes with spleen cells or with peripheral blood leukocytes were assayed for their ability to respond to PHA or to produce a graft-vs-host reaction in embryonic chicks. These studies indicated that immunoregulatory cells exist in chicken thymus, which displays both helper and suppressor activity. The suppressor cells were more prevalent or more easily detectable in young birds and in chickens with intact bursas. The helper function of thymocytes was seen to better advantage with cells derived from older animals and from bursectomized donors."}
{"id": "PMID:19536", "title": "Immune responses during measles infection in immunosuppressed Rhesus monkeys.", "content": "Rhesus monkeys immunosuppressed with horse anti-human thymocyte gamma-globulin (ATG) were infected with measles and simultaneously inoculated with sheep erythrocytes (SRBC), a thymus-dependent antigen, and with pneumococcal polysaccaride type III (SSS-III), a thymus-independent antigen. ATG treatment alone suppressed SRBC antibody production, had no effect on SSS-III antibody production, and effectively eliminated circulating T cells compared to nonsuppressed monkeys. ATG treatment of measles-infected monkeys resulted in delayed virus clearance and delayed antibody production compared to nonsuppressed infected monkeys. After cessation of ATG treatment, measles antibodies and T cells reached normal levels, and measles virus was eliminated. Thus, immune clearance of measles virus is T cell-dependent, but the relative roles of cellular- and humoral-mediated immunity in vivo could not be clearly separated. Also, measles infection was associated with a decreased T cell mitogen responsiveness of circulating lymphocytes but not of lymph node lymphocytes, suggesting an altered circulating pattern of the cells responsible for delayed hypersensitivity. Also, measles infection had no effect on T-dependent antibody production to SRBC.", "contents": "Immune responses during measles infection in immunosuppressed Rhesus monkeys. Rhesus monkeys immunosuppressed with horse anti-human thymocyte gamma-globulin (ATG) were infected with measles and simultaneously inoculated with sheep erythrocytes (SRBC), a thymus-dependent antigen, and with pneumococcal polysaccaride type III (SSS-III), a thymus-independent antigen. ATG treatment alone suppressed SRBC antibody production, had no effect on SSS-III antibody production, and effectively eliminated circulating T cells compared to nonsuppressed monkeys. ATG treatment of measles-infected monkeys resulted in delayed virus clearance and delayed antibody production compared to nonsuppressed infected monkeys. After cessation of ATG treatment, measles antibodies and T cells reached normal levels, and measles virus was eliminated. Thus, immune clearance of measles virus is T cell-dependent, but the relative roles of cellular- and humoral-mediated immunity in vivo could not be clearly separated. Also, measles infection was associated with a decreased T cell mitogen responsiveness of circulating lymphocytes but not of lymph node lymphocytes, suggesting an altered circulating pattern of the cells responsible for delayed hypersensitivity. Also, measles infection had no effect on T-dependent antibody production to SRBC."}
{"id": "PMID:19538", "title": "Cross-protective immunity to Gram-negative bacilli: studies with core glycolipid of Salmonella minnesota and antigens of Streptococcus pneumoniae.", "content": "Two immunoprophylactic approaches to the control of infections caused by gramnegative bacilli were evaluated by study of experimental infections in animals. The core glycolipid antigen derived from the Re mutant of Salmonella minnesota R595 is shared by virtually all enteric bacteria, and immunization with this endotoxin protects against the hemodynamic sequelae of bacterial infection and pyrexia without enhancing intravascular clearance of bacteria. The degree of protection afforded by active and passive immunization with core glycolipid was significantly less than that conferred by type-specific immunization. Escherichia coli and Klebsiella pneumoniae share capsular antigens with some strains of Streptococcus pneumoniae; by the mechanism of enhanced opsonization, antibodies to S. pneumoniae may cross-protect against infection with E. coli or K. pneumoniae.", "contents": "Cross-protective immunity to Gram-negative bacilli: studies with core glycolipid of Salmonella minnesota and antigens of Streptococcus pneumoniae. Two immunoprophylactic approaches to the control of infections caused by gramnegative bacilli were evaluated by study of experimental infections in animals. The core glycolipid antigen derived from the Re mutant of Salmonella minnesota R595 is shared by virtually all enteric bacteria, and immunization with this endotoxin protects against the hemodynamic sequelae of bacterial infection and pyrexia without enhancing intravascular clearance of bacteria. The degree of protection afforded by active and passive immunization with core glycolipid was significantly less than that conferred by type-specific immunization. Escherichia coli and Klebsiella pneumoniae share capsular antigens with some strains of Streptococcus pneumoniae; by the mechanism of enhanced opsonization, antibodies to S. pneumoniae may cross-protect against infection with E. coli or K. pneumoniae."}
{"id": "PMID:19539", "title": "Comparison otitis media due to types 3 and 23 Streptococcus pneumoniae in the Chinchilla model.", "content": "Only a few pneumococcal serotypes are responsible for the majority of cases of acute otitis media due to Streptococcus pneumoniae in children. The immunopathogenesis of otitis media cause by two serotypes, type 3 and 23, was studied in chinchillas. Chinchillas with type 23 pneumococcal otitis media were capable of clearing the infection over a six-week period without treatment, whereas the type 3 infection persisted throughout the six-week study. In addition, bacteremia or meningitis occurred more frequently and earlier with type 3 pneumococcal otitis media than with type 23. The resolution of the type 23 pneumococcal infection paralleled the development of type-specific antibody, as measured by radioimmunoassay, whereas type 3 infection was associated with a fall in serum antibody to low levels. Since the pathogenesis of pneumococcal otitis media in the chinchilla differs between pneumococcal serotypes, it may be important to correlate pneumococcal serotypes with sequealae and recurrence of otitis media in children.", "contents": "Comparison otitis media due to types 3 and 23 Streptococcus pneumoniae in the Chinchilla model. Only a few pneumococcal serotypes are responsible for the majority of cases of acute otitis media due to Streptococcus pneumoniae in children. The immunopathogenesis of otitis media cause by two serotypes, type 3 and 23, was studied in chinchillas. Chinchillas with type 23 pneumococcal otitis media were capable of clearing the infection over a six-week period without treatment, whereas the type 3 infection persisted throughout the six-week study. In addition, bacteremia or meningitis occurred more frequently and earlier with type 3 pneumococcal otitis media than with type 23. The resolution of the type 23 pneumococcal infection paralleled the development of type-specific antibody, as measured by radioimmunoassay, whereas type 3 infection was associated with a fall in serum antibody to low levels. Since the pathogenesis of pneumococcal otitis media in the chinchilla differs between pneumococcal serotypes, it may be important to correlate pneumococcal serotypes with sequealae and recurrence of otitis media in children."}
{"id": "PMID:19540", "title": "Maturation of regulatory factors influencing magnitude of antibody response to capsular polysaccharide of type III Streptococcus pneumoniae.", "content": "Mice of different ages were evaluated for their ability to give a plaque-forming cell response to the capsular polysaccharide of Streptococcus pneumoniae (SSS-III). The response of amplifier and suppressor thymus-derived (T-) cells was also evaluated. The responses to an optimally immunogenic dose of SSS-III for two-and three-week-old mice were only 7% and 14%, respectively, of that produced by adult mice; values comparable to those of adult mice were attained by four weeks of age. Activity of amplifier T-cells, which was minimal at two to four weeks of age, matured slowly and did not reach a maximum until eight to 10 weeks of age. However, activity of suppressor T-cells was found to be fully developed as early as two weeks of age. These findings indicate that the inhibitory effects of suppressor T-cells are predominant in young mice and that such cells may play an active role in determining the ease with which immunological unresponsiveness is induced in neonates.", "contents": "Maturation of regulatory factors influencing magnitude of antibody response to capsular polysaccharide of type III Streptococcus pneumoniae. Mice of different ages were evaluated for their ability to give a plaque-forming cell response to the capsular polysaccharide of Streptococcus pneumoniae (SSS-III). The response of amplifier and suppressor thymus-derived (T-) cells was also evaluated. The responses to an optimally immunogenic dose of SSS-III for two-and three-week-old mice were only 7% and 14%, respectively, of that produced by adult mice; values comparable to those of adult mice were attained by four weeks of age. Activity of amplifier T-cells, which was minimal at two to four weeks of age, matured slowly and did not reach a maximum until eight to 10 weeks of age. However, activity of suppressor T-cells was found to be fully developed as early as two weeks of age. These findings indicate that the inhibitory effects of suppressor T-cells are predominant in young mice and that such cells may play an active role in determining the ease with which immunological unresponsiveness is induced in neonates."}
{"id": "PMID:19541", "title": "Temperature-sensitive mutants of type I Streptococcus pneumoniae: preparation, characterization, and evidence for attenuation and immunogenicity.", "content": "Thirteen temperature-sensitive (ts) mutants of type I Streptococcus pneumoniae were selected after exposure of virulent wild-type (ts+) organisms to nitrosoguanidine. Each mutant resembled the ts+ parent in properties of alpha-hemolysis, bile solubility, optochin sensitivity, antibiotic sensitivity, and serotype. Unlike the ts+ parent, however, each ts mutant was restricted in its capacity to form colonies on blood agar at 38 C. With the exception of two mutants, there was a correlation between the degree of temperature-sensitivity of a mutant and its genetic stability. When inoculated intraperitoneally into mice, 11 of 13 mutants were attenuated and induced homologous resistance. Three mutants (ts 1, ts 3, and ts 4) were also studied in hamsters and were found to be attenuated and immunogenic after intraperitoneal injection. Study of the behavior of mutants ts 1, ts 3, and ts 4 in the blood of hamsters suggested that attenuation may be related, in part, to decreased growth and survival of ts organisms at body temperature. Mutants ts 1 and ts 4 were completely attenuated for hamsters when administered intranasally and induced significant resistance to subsequent challenge with wild-type organisms by the same route. Local administration of ts mutants of type 1 S. pneumoniae to hamsters may provide a model for evaluating the potential of live vaccines in the prevention of disease due to bacterial respiratory tract pathogens.", "contents": "Temperature-sensitive mutants of type I Streptococcus pneumoniae: preparation, characterization, and evidence for attenuation and immunogenicity. Thirteen temperature-sensitive (ts) mutants of type I Streptococcus pneumoniae were selected after exposure of virulent wild-type (ts+) organisms to nitrosoguanidine. Each mutant resembled the ts+ parent in properties of alpha-hemolysis, bile solubility, optochin sensitivity, antibiotic sensitivity, and serotype. Unlike the ts+ parent, however, each ts mutant was restricted in its capacity to form colonies on blood agar at 38 C. With the exception of two mutants, there was a correlation between the degree of temperature-sensitivity of a mutant and its genetic stability. When inoculated intraperitoneally into mice, 11 of 13 mutants were attenuated and induced homologous resistance. Three mutants (ts 1, ts 3, and ts 4) were also studied in hamsters and were found to be attenuated and immunogenic after intraperitoneal injection. Study of the behavior of mutants ts 1, ts 3, and ts 4 in the blood of hamsters suggested that attenuation may be related, in part, to decreased growth and survival of ts organisms at body temperature. Mutants ts 1 and ts 4 were completely attenuated for hamsters when administered intranasally and induced significant resistance to subsequent challenge with wild-type organisms by the same route. Local administration of ts mutants of type 1 S. pneumoniae to hamsters may provide a model for evaluating the potential of live vaccines in the prevention of disease due to bacterial respiratory tract pathogens."}
{"id": "PMID:19542", "title": "Adenyl cyclase in Bordetella pertussis vaccines.", "content": "Brodetella pertussis organisms have a large amount of extracytoplasmic adenyl cyclase, part of which is found in the supernatant culture medium during exponential growth. The enzyme differs from previously studied bacterial adenyl cyclases in biochemical characteristics as well as in location. Several commercial pertussis vaccines were found to contain adenyl cyclase activity; this activity is probably due to the extracytoplasmic enzyme associated with and released from the whole cells in the vaccine.", "contents": "Adenyl cyclase in Bordetella pertussis vaccines. Brodetella pertussis organisms have a large amount of extracytoplasmic adenyl cyclase, part of which is found in the supernatant culture medium during exponential growth. The enzyme differs from previously studied bacterial adenyl cyclases in biochemical characteristics as well as in location. Several commercial pertussis vaccines were found to contain adenyl cyclase activity; this activity is probably due to the extracytoplasmic enzyme associated with and released from the whole cells in the vaccine."}
{"id": "PMID:19543", "title": "Prevention of pneumococcal infection by immunization with capsular polysaccharides of Streptococcus pneumoniae: current status of polyvalent vaccines.", "content": "Because of the continuing morbidity and mortality resulting from pneumococcal infection, a program was instituted to redevelop polyvalent vaccines consisting of capsular polysaccharides of Streptococcus pneumoniae. Vaccines containing 50 microgram each of the capsular polysaccharides of as many as 13 pneumococcal types have been shown to be safe, antigenic, and 78.5% effective in the prevention of type-specific putative pneumococcal pneumonia and of type-specific pneumococcal bacteremia in adults. In a population in which pneumococcal pneumonia predominated, the total incidence of radiologically confirmed pneumonia, irrespective of cause, was reduced by 54.3% by use of a tridecavalent vaccine. The efficacy of vaccine in the prevention of infection during the first two years of life is under investigation. The vaccine is recommended for those at high risk of pneumococcal infection or of a fatal outcome from such illness.", "contents": "Prevention of pneumococcal infection by immunization with capsular polysaccharides of Streptococcus pneumoniae: current status of polyvalent vaccines. Because of the continuing morbidity and mortality resulting from pneumococcal infection, a program was instituted to redevelop polyvalent vaccines consisting of capsular polysaccharides of Streptococcus pneumoniae. Vaccines containing 50 microgram each of the capsular polysaccharides of as many as 13 pneumococcal types have been shown to be safe, antigenic, and 78.5% effective in the prevention of type-specific putative pneumococcal pneumonia and of type-specific pneumococcal bacteremia in adults. In a population in which pneumococcal pneumonia predominated, the total incidence of radiologically confirmed pneumonia, irrespective of cause, was reduced by 54.3% by use of a tridecavalent vaccine. The efficacy of vaccine in the prevention of infection during the first two years of life is under investigation. The vaccine is recommended for those at high risk of pneumococcal infection or of a fatal outcome from such illness."}
{"id": "PMID:19545", "title": "Platelet-aggregating factor and the aggregation of fixed washed platelets.", "content": "Platelet-aggregating factor (PAF) was removed from bovine plasma by human platelets fixed with 2% formaldehyde. The degree of adsorption was directly related to the platelet concentration and the length of incubation. Fixed washed platelets (FWP) aggregated with bovine plasma could be deaggregated by 1M KCl, Evans blue, and 8M urea but not by beta-galactosidase. Incubation with 1M KCl eluted some but not all of the PAF, as the deaggregated platelets spontaneously aggregated upon removal of the deaggregating conditions. Also, fixed platelets adsorbed PAF even in the presence of 1M salt or after treatment with Evans blue. Platelet aggregation was not affected by thrombin (20 micron/ml) but was abolished by trypsin at concentrations as low as 4 X 10(-1) microgram/ml. The data suggest that deaggregation is not the result of elution of the loosely bound aggregating factor from the platelet surface, but rather the disruption of noncovalent interplatelet bridging between one or more PAF molecules bound to a specific receptor.", "contents": "Platelet-aggregating factor and the aggregation of fixed washed platelets. Platelet-aggregating factor (PAF) was removed from bovine plasma by human platelets fixed with 2% formaldehyde. The degree of adsorption was directly related to the platelet concentration and the length of incubation. Fixed washed platelets (FWP) aggregated with bovine plasma could be deaggregated by 1M KCl, Evans blue, and 8M urea but not by beta-galactosidase. Incubation with 1M KCl eluted some but not all of the PAF, as the deaggregated platelets spontaneously aggregated upon removal of the deaggregating conditions. Also, fixed platelets adsorbed PAF even in the presence of 1M salt or after treatment with Evans blue. Platelet aggregation was not affected by thrombin (20 micron/ml) but was abolished by trypsin at concentrations as low as 4 X 10(-1) microgram/ml. The data suggest that deaggregation is not the result of elution of the loosely bound aggregating factor from the platelet surface, but rather the disruption of noncovalent interplatelet bridging between one or more PAF molecules bound to a specific receptor."}
{"id": "PMID:19547", "title": "A comparison of lipoprotein lipase activity and adipocyte differentiation in growing male rats.", "content": "During adipose tissue development changes in lipoprotein lipase activity per adipocyte precede significant changes in fat cell size. Lipoprotein lipase activity per adipocyte increases fourfold from the second to seventh postnatal week. Furthermore, when isolated adipocytes and stromal--vascular cells are prepared by collagenase digestion of adipose tissue, there is a progressive shift in enzyme activity during development from the stromal-vascular compartment to the adipocyte fraction. The data support the concept that during normal development a \"bed\" of preadipocytes is synthesized during the suckling period. The data further suggest a regulatory role for lipoprotein lipase in the control of \"lipid-filling\" during early postnatal development.", "contents": "A comparison of lipoprotein lipase activity and adipocyte differentiation in growing male rats. During adipose tissue development changes in lipoprotein lipase activity per adipocyte precede significant changes in fat cell size. Lipoprotein lipase activity per adipocyte increases fourfold from the second to seventh postnatal week. Furthermore, when isolated adipocytes and stromal--vascular cells are prepared by collagenase digestion of adipose tissue, there is a progressive shift in enzyme activity during development from the stromal-vascular compartment to the adipocyte fraction. The data support the concept that during normal development a \"bed\" of preadipocytes is synthesized during the suckling period. The data further suggest a regulatory role for lipoprotein lipase in the control of \"lipid-filling\" during early postnatal development."}
{"id": "PMID:19548", "title": "Blood respiratory properties of rainbow trout (Salmo gairdneri) kept in water of high CO2 tension.", "content": "1. Blood O2 transport and acid-base balance were studied at 20 degrees C in rainbow trout (Salmo gairdneri) which had been kept in water of high CO2 content (15 mmHg) for at least a week. Also the blood gas chemistry of fish rapidly entering or leaving the hypercapnic environment was studied. 2. Fish entering high CO2 water suffered a sharp decrease in blood pH which significantly reduced O2 transport by the blood, but after a few hours considerable compensation was achieved. 3. After at least a week in high CO2 water, trout showed elevated plasma bicarbonate and PCO2 levels, and a decrease in plasma chloride, while pH was about 0 - 1 pH unit below the level for control fish. Oxygen transport by the blood was marginally reduced. 4. Hypercapnic fish rapidly entering fresh water showed a sharp increase in blood pH and a decrease in blood PO2. These parameters regained normal values after a few hours but plasma bicarbonate and chloride levels took much longer to regain control concentrations. 5. Acid-base balance in hypercapnic fish is discussed with particular reference to the role of the branchial ion exchanges.", "contents": "Blood respiratory properties of rainbow trout (Salmo gairdneri) kept in water of high CO2 tension. 1. Blood O2 transport and acid-base balance were studied at 20 degrees C in rainbow trout (Salmo gairdneri) which had been kept in water of high CO2 content (15 mmHg) for at least a week. Also the blood gas chemistry of fish rapidly entering or leaving the hypercapnic environment was studied. 2. Fish entering high CO2 water suffered a sharp decrease in blood pH which significantly reduced O2 transport by the blood, but after a few hours considerable compensation was achieved. 3. After at least a week in high CO2 water, trout showed elevated plasma bicarbonate and PCO2 levels, and a decrease in plasma chloride, while pH was about 0 - 1 pH unit below the level for control fish. Oxygen transport by the blood was marginally reduced. 4. Hypercapnic fish rapidly entering fresh water showed a sharp increase in blood pH and a decrease in blood PO2. These parameters regained normal values after a few hours but plasma bicarbonate and chloride levels took much longer to regain control concentrations. 5. Acid-base balance in hypercapnic fish is discussed with particular reference to the role of the branchial ion exchanges."}
{"id": "PMID:19549", "title": "pH and haemoglobin oxygen affinity in blood from the Antarctic cod Dissostichus mawsoni.", "content": "Blood pH in the antarctic cod (Dissostichus mawsoni) and in two Trematomus species, occlrring at --1-9 degrees C, is extremely high (approximately 8-2 to 8-3). This supports and extends Rahn's (1966) model for the temperature-pH relationship in cold-blooded vertebrates. The blood of D. mawsoni shows a low oxygen affinity (P50 approximately equal to 14-5 mmHg at pH 8-16 and -1-9 degrees C). Despite normal in vitro temperature and pH sensitivities, blood P50 increases only slightly when live fish are temperature-stressed (+ 4-0 degrees C), or become acidotic as a result of agitational stress (blood pH 7-71), primarily as a result of compensatory decreases in blood ATP levels. Oxygen-binding properties of 'stripped' (cofactor-free) solutions of D. mawsoni haemoglobin were measured in attempts to elucidate the molecular mechanisms involved in the function of the pigment.", "contents": "pH and haemoglobin oxygen affinity in blood from the Antarctic cod Dissostichus mawsoni. Blood pH in the antarctic cod (Dissostichus mawsoni) and in two Trematomus species, occlrring at --1-9 degrees C, is extremely high (approximately 8-2 to 8-3). This supports and extends Rahn's (1966) model for the temperature-pH relationship in cold-blooded vertebrates. The blood of D. mawsoni shows a low oxygen affinity (P50 approximately equal to 14-5 mmHg at pH 8-16 and -1-9 degrees C). Despite normal in vitro temperature and pH sensitivities, blood P50 increases only slightly when live fish are temperature-stressed (+ 4-0 degrees C), or become acidotic as a result of agitational stress (blood pH 7-71), primarily as a result of compensatory decreases in blood ATP levels. Oxygen-binding properties of 'stripped' (cofactor-free) solutions of D. mawsoni haemoglobin were measured in attempts to elucidate the molecular mechanisms involved in the function of the pigment."}
{"id": "PMID:19550", "title": "The effect of progressive hypoxia on respiration in the toad Bufo marinus.", "content": "1. As Bufo marinus became progressively hypoxic over a period of 90 min, there was a rise in arterial pH, presumably brought about by hyperventilation. The alkalosis gradually disappeared when oxygen levels became very low. It is suggested that this is the result of a respiratory or a metabolic pH adjustment, or both. 2. Hypoxic animals developed a characteristic breathing pattern in which discrete periods of lung ventilations alternated with buccal oscillations or respiratory pauses. 3. A pronounced bradycardia was associated with the concomitant decline of inspired and arterial PO2. 4. Although respiratory rates were greater than normal resting values in the initial stages of post-hypoxia, the pre-exposure breathing pattern was quickly restored. Following recovery from bradycardia (60 min), the breathing rates, arterial blood gases and pHa returned to normal within 30 min.", "contents": "The effect of progressive hypoxia on respiration in the toad Bufo marinus. 1. As Bufo marinus became progressively hypoxic over a period of 90 min, there was a rise in arterial pH, presumably brought about by hyperventilation. The alkalosis gradually disappeared when oxygen levels became very low. It is suggested that this is the result of a respiratory or a metabolic pH adjustment, or both. 2. Hypoxic animals developed a characteristic breathing pattern in which discrete periods of lung ventilations alternated with buccal oscillations or respiratory pauses. 3. A pronounced bradycardia was associated with the concomitant decline of inspired and arterial PO2. 4. Although respiratory rates were greater than normal resting values in the initial stages of post-hypoxia, the pre-exposure breathing pattern was quickly restored. Following recovery from bradycardia (60 min), the breathing rates, arterial blood gases and pHa returned to normal within 30 min."}
{"id": "PMID:19551", "title": "Suppression of in vitro cytotoxic response by macrophages due to induced arginase.", "content": "Arginine was found to be completely depleted from cell-free supernates of mixed leukocyte cultures suppressed by the addition of excess macrophages. Partial reversal of macrophage-mediated suppression was accomplished by daily addition of a cocktail containing arginine and nonamino acid nutrients. Complete reversal of the suppression was accomplished by the addition of arginine and glucose to the medium and the nonadherent cells after their separation from the adherent macrophages. A marked increase in the enzyme arginase was found in macrophages that had been cultured 24 h in vitro in Eagle's minimum essential medium plus 10% fetal calf serum, in peritoneal cells activated by prior injection of thioglycollate, and in one spleen activated by a graft vs. host reaction.", "contents": "Suppression of in vitro cytotoxic response by macrophages due to induced arginase. Arginine was found to be completely depleted from cell-free supernates of mixed leukocyte cultures suppressed by the addition of excess macrophages. Partial reversal of macrophage-mediated suppression was accomplished by daily addition of a cocktail containing arginine and nonamino acid nutrients. Complete reversal of the suppression was accomplished by the addition of arginine and glucose to the medium and the nonadherent cells after their separation from the adherent macrophages. A marked increase in the enzyme arginase was found in macrophages that had been cultured 24 h in vitro in Eagle's minimum essential medium plus 10% fetal calf serum, in peritoneal cells activated by prior injection of thioglycollate, and in one spleen activated by a graft vs. host reaction."}
{"id": "PMID:19552", "title": "Elastase secretion by peritoneal exudative and alveolar macrophages.", "content": "Mouse alveolar macrophages (AM) cultured in the absence of serum secrete an elastolytic enzyme. The elastase from AM resembles the previously described elastase from peritoneal macrophages (PM) in pH optimum and inhibition profile. The macrophage enzymes do not appear to be stored, and with periodic changes in the culture medium, accumulate extracellularly for up to 10 days. Resident PM produce barely detectable levels of extracellular elastase unless given a phagocytic load. Thioglycollate-stimulated peritoneal exudative macrophages (PEM), however, secret easily detectable levels of elastase, which can be further increased with a phagocytic load. Without any additional stimulation, AM secret an elastolytic activity comparable to that of the PEM receiving a phagocytic load, but unlike PM they do not increase elastase secretion after phagocytosis.", "contents": "Elastase secretion by peritoneal exudative and alveolar macrophages. Mouse alveolar macrophages (AM) cultured in the absence of serum secrete an elastolytic enzyme. The elastase from AM resembles the previously described elastase from peritoneal macrophages (PM) in pH optimum and inhibition profile. The macrophage enzymes do not appear to be stored, and with periodic changes in the culture medium, accumulate extracellularly for up to 10 days. Resident PM produce barely detectable levels of extracellular elastase unless given a phagocytic load. Thioglycollate-stimulated peritoneal exudative macrophages (PEM), however, secret easily detectable levels of elastase, which can be further increased with a phagocytic load. Without any additional stimulation, AM secret an elastolytic activity comparable to that of the PEM receiving a phagocytic load, but unlike PM they do not increase elastase secretion after phagocytosis."}
{"id": "PMID:19553", "title": "Influence of splenectomy on first set rejection reactions of C57BL/6 females to male skin isografts.", "content": "The tempo with which C57BL/6 females reject male skin isografts is determined in part by the immunogenicity of the H-Y antigen and in part by the capacity of the host to respond immunologically. Our studies indicate that the spleen plays an important role in determining the briskness of the rejection process in that splenectomy 7-30 days before grafting with male skin significantly shortens the survival time. The results of reconstitution experiments suggests that a population of cells is present in spleens of normal, but not specifically sensitized, females which can restore the conventional first set reaction in splenectomized females. It is inferred that this resident population normally operates in spleen-intact females to delay the development of specific effector responses. Lymphoid cells from H-Y antigen-sensitized, splenectomized females failed to evoke graft-vs.-host responses in males whereas similar cells from females with spleens intact did possess graft-vs.-host potential.", "contents": "Influence of splenectomy on first set rejection reactions of C57BL/6 females to male skin isografts. The tempo with which C57BL/6 females reject male skin isografts is determined in part by the immunogenicity of the H-Y antigen and in part by the capacity of the host to respond immunologically. Our studies indicate that the spleen plays an important role in determining the briskness of the rejection process in that splenectomy 7-30 days before grafting with male skin significantly shortens the survival time. The results of reconstitution experiments suggests that a population of cells is present in spleens of normal, but not specifically sensitized, females which can restore the conventional first set reaction in splenectomized females. It is inferred that this resident population normally operates in spleen-intact females to delay the development of specific effector responses. Lymphoid cells from H-Y antigen-sensitized, splenectomized females failed to evoke graft-vs.-host responses in males whereas similar cells from females with spleens intact did possess graft-vs.-host potential."}
{"id": "PMID:19554", "title": "[Critical observations on the use of phenolphthalein monophosphate as a substrate for the determination of prostatic acid phosphatase (author's transl)].", "content": "At pH 10, which is in the alkaline measurement range, phenolphthalein is bound by albumin. The resonance system of this acid-base indicator cannot therefore be completely formed, and the colour intensity is correspondingly lower. Albumin also binds phenolphthalein monophosphate at pH 4-8, in the pH range of the enzymic reaction. Depending on the relative concentrations, the substrate concentration is therefore either suboptimal (manifested as a lower catalytic concentration of phosphatase), or the substrate excess is bound by albumin, so that the substrate inhibition of the phosphatase is decreased or abolished. Binding of phenolphthalein and its monophosphate to albumin is partly prevented by the addition of alcohol. These results show that the determination of prostate phosphatase with the substrate phenolphthalein monophosphate is markedly influenced by various factors. The interpretation of the observed colour intensity is therefore difficult, and the calculation of the catalytic concentration is frequently subject to error.", "contents": "[Critical observations on the use of phenolphthalein monophosphate as a substrate for the determination of prostatic acid phosphatase (author's transl)]. At pH 10, which is in the alkaline measurement range, phenolphthalein is bound by albumin. The resonance system of this acid-base indicator cannot therefore be completely formed, and the colour intensity is correspondingly lower. Albumin also binds phenolphthalein monophosphate at pH 4-8, in the pH range of the enzymic reaction. Depending on the relative concentrations, the substrate concentration is therefore either suboptimal (manifested as a lower catalytic concentration of phosphatase), or the substrate excess is bound by albumin, so that the substrate inhibition of the phosphatase is decreased or abolished. Binding of phenolphthalein and its monophosphate to albumin is partly prevented by the addition of alcohol. These results show that the determination of prostate phosphatase with the substrate phenolphthalein monophosphate is markedly influenced by various factors. The interpretation of the observed colour intensity is therefore difficult, and the calculation of the catalytic concentration is frequently subject to error."}
{"id": "PMID:19555", "title": "Relations between ameboid movement and membrane-controlled electrical currents.", "content": "We have studied the pattern of electrical currents through amebas (mainly Chaos chaos) with an ultrasensitive extracellular vibrating probe. Amebas drive both steady currents and current pulses through themselves. Relatively steady current with an average surface density of 0.1-0.2 muA/cm2 enters the rear quarter of an ameba and leaves its pseudopods. Streaming reversals are preceded by changes in this current pattern and the region with the largest new inward current becomes the new tail. Ion substitution studies suggest that some of the steady inward current is carried by calcium ions. Characteristic stimulated pulses of current sometimes follow the close approach of the vibrating probe to the side of an advancing pseudopod. Such a pulse enters the cytoplasm through a small patch of membrane near the probe (and seems to leave through the adjacent membrane), is usually followed by hyaline cap and then by pseudopod initiation, is calcium dependent, lasts about 5-10 s, and has a peak density of about 0.4 muA/cm2. Spontaneous pulses of similar shape and duration may enter or leave any part of an animal. They are much less localized, tend to have higher peak densities, and occur in physiological salt solutions at about 0.2-4 times per minute. Retraction of a pseudopod is always accompanied or preceded by a spontaneous pulse which leaves its sides.", "contents": "Relations between ameboid movement and membrane-controlled electrical currents. We have studied the pattern of electrical currents through amebas (mainly Chaos chaos) with an ultrasensitive extracellular vibrating probe. Amebas drive both steady currents and current pulses through themselves. Relatively steady current with an average surface density of 0.1-0.2 muA/cm2 enters the rear quarter of an ameba and leaves its pseudopods. Streaming reversals are preceded by changes in this current pattern and the region with the largest new inward current becomes the new tail. Ion substitution studies suggest that some of the steady inward current is carried by calcium ions. Characteristic stimulated pulses of current sometimes follow the close approach of the vibrating probe to the side of an advancing pseudopod. Such a pulse enters the cytoplasm through a small patch of membrane near the probe (and seems to leave through the adjacent membrane), is usually followed by hyaline cap and then by pseudopod initiation, is calcium dependent, lasts about 5-10 s, and has a peak density of about 0.4 muA/cm2. Spontaneous pulses of similar shape and duration may enter or leave any part of an animal. They are much less localized, tend to have higher peak densities, and occur in physiological salt solutions at about 0.2-4 times per minute. Retraction of a pseudopod is always accompanied or preceded by a spontaneous pulse which leaves its sides."}
{"id": "PMID:19556", "title": "Temperature-dependent changes of chloride transport kinetics in human red cells.", "content": "Chloride self-exchange in human red cells was studied between 0 degrees C and 38 degrees C. At higher temperatures the flow-tube method was used. Although the general features of chloride transport at 0 degrees C and 38 degrees C are similar, the following differences were found: (a) the maximum pH of chloride self-exchange flux was lowered 0.6 pH unit from 7.8 to 7.2 when temperature was increased from 0 degrees C to 38 degrees C; (b)the apparent half-saturation constant increased from 28 mM at 0 degrees C to 65 mM at 38 degrees C; (c) chloride transport at body temperature is slower than predicted by other investigators by extrapolation from low-temperature results. Chloride transport increased only 200 times when temperature was raised from 0 degrees C to 38 degrees C, because the apparent activation energy decreased from 30 kcal mol(-1) to 20 kcal mol(-1) above a temperature of 15 degrees C; (d) a study of temperature dependence of the slower bromide self-exchange showed that a similar change of activation energy occurred around 25 degrees C. Both in the case of Cl(-) (15 degrees C) and in the case of Br(-) (25 degrees C), critical temperature was reached when the anion self-exchange had a turnover number of about 4x10(9) ions cell (-1)s(-1); (e) inhibition of chloride transport by DIDS (4,4'- diisothiocyano-stilbene-2,2'-disulfonate)revealed that the deflection persisted at 15 degrees C at partial inhibition (66 percent) presumably because DIDS inactivated 66 percent of the transport sites. It is suggested that a less temperature- dependent step of anion exchange becomes rate limiting at the temperature where a critical turnover number is reached.", "contents": "Temperature-dependent changes of chloride transport kinetics in human red cells. Chloride self-exchange in human red cells was studied between 0 degrees C and 38 degrees C. At higher temperatures the flow-tube method was used. Although the general features of chloride transport at 0 degrees C and 38 degrees C are similar, the following differences were found: (a) the maximum pH of chloride self-exchange flux was lowered 0.6 pH unit from 7.8 to 7.2 when temperature was increased from 0 degrees C to 38 degrees C; (b)the apparent half-saturation constant increased from 28 mM at 0 degrees C to 65 mM at 38 degrees C; (c) chloride transport at body temperature is slower than predicted by other investigators by extrapolation from low-temperature results. Chloride transport increased only 200 times when temperature was raised from 0 degrees C to 38 degrees C, because the apparent activation energy decreased from 30 kcal mol(-1) to 20 kcal mol(-1) above a temperature of 15 degrees C; (d) a study of temperature dependence of the slower bromide self-exchange showed that a similar change of activation energy occurred around 25 degrees C. Both in the case of Cl(-) (15 degrees C) and in the case of Br(-) (25 degrees C), critical temperature was reached when the anion self-exchange had a turnover number of about 4x10(9) ions cell (-1)s(-1); (e) inhibition of chloride transport by DIDS (4,4'- diisothiocyano-stilbene-2,2'-disulfonate)revealed that the deflection persisted at 15 degrees C at partial inhibition (66 percent) presumably because DIDS inactivated 66 percent of the transport sites. It is suggested that a less temperature- dependent step of anion exchange becomes rate limiting at the temperature where a critical turnover number is reached."}
{"id": "PMID:19557", "title": "Preferential hemolysis of postnatal calf red cells induced by internal alkalinization.", "content": "Red blood cells from neonatal calves, but not from adult cows, rapidly hemolyze in buffered 300 mM solutions of a variety of nonelectrolytes and amino acids. Of these compounds, sucrose is chosen to elucidate the mechanism by which this preferential hemolysis takes place. As in other mammalian red cells, both calf and cow cells are found to be impermeable to sucrose and, in an isosmolar sucrose solution, to undergo volume shrinkage caused by the net loss of chloride ions with concomitant increase in intracellular pH. To test the potential role of intracellular pH change associated with chloride loss in promoting hemolysis, intracellular pH was altered by: (a) a direct addition of fixed acid or base to sucrose solution; (b) the removal of dissolved CO(2) from sucrose solution; and (c) the addition of cells to isotonic NaHCO(3) solution in the absence of sucrose. In all cases, only calf and not cow cells underwent hemolysis. Moreover, 4-acetamido-4'-isothiocyano-2,2'-stilbene disulfonic acid, a potent anion transport inhibitor, completely protected calf cells from hemolysis and caused a nearly total inhibition of both chloride loss and intracellular alkalinization. Furthermore, the hemolytic process is closely related to the integrity of a membrane protein, the band 3 protein, which can be cleaved to varying degrees by the combined treatment of pronase and lipase. Hemolysis is progressively inhibited as the band 3 protein undergoes proteolysis, until a total inhibition of hemolysis takes place when almost all of the band 3 protein is digested into smaller protein components with a mol wt of 65,000 and 35,000 daltons. These results suggest that the intracellular alkalinization process leading to a structural instability of the membrane band 3 protein is responsible for this calf cell hemolysis.", "contents": "Preferential hemolysis of postnatal calf red cells induced by internal alkalinization. Red blood cells from neonatal calves, but not from adult cows, rapidly hemolyze in buffered 300 mM solutions of a variety of nonelectrolytes and amino acids. Of these compounds, sucrose is chosen to elucidate the mechanism by which this preferential hemolysis takes place. As in other mammalian red cells, both calf and cow cells are found to be impermeable to sucrose and, in an isosmolar sucrose solution, to undergo volume shrinkage caused by the net loss of chloride ions with concomitant increase in intracellular pH. To test the potential role of intracellular pH change associated with chloride loss in promoting hemolysis, intracellular pH was altered by: (a) a direct addition of fixed acid or base to sucrose solution; (b) the removal of dissolved CO(2) from sucrose solution; and (c) the addition of cells to isotonic NaHCO(3) solution in the absence of sucrose. In all cases, only calf and not cow cells underwent hemolysis. Moreover, 4-acetamido-4'-isothiocyano-2,2'-stilbene disulfonic acid, a potent anion transport inhibitor, completely protected calf cells from hemolysis and caused a nearly total inhibition of both chloride loss and intracellular alkalinization. Furthermore, the hemolytic process is closely related to the integrity of a membrane protein, the band 3 protein, which can be cleaved to varying degrees by the combined treatment of pronase and lipase. Hemolysis is progressively inhibited as the band 3 protein undergoes proteolysis, until a total inhibition of hemolysis takes place when almost all of the band 3 protein is digested into smaller protein components with a mol wt of 65,000 and 35,000 daltons. These results suggest that the intracellular alkalinization process leading to a structural instability of the membrane band 3 protein is responsible for this calf cell hemolysis."}
{"id": "PMID:19558", "title": "Influence of solute and hydrogen ion concentration on the water relations of some xerophilic fungi.", "content": "Germination and growth of six xerophilic fungi, Aspergillus flavus, Aspergillus ochraceus, Eurotium chevalieri, Chrysosphorium fastidium, Wallemia sebi and Xeromyces bisporus were examined on media of a wide range of water activities (aw). The influence of three solutes, NaCl, glycerol and a glucose/fructose mixture, was studied at pH 4-0 and pH 6-5 using a plate-slide technique. Germination times and growth rates were affected by solute type, but the influence of pH was less marked. Except for Wallemia sebi, the fungi grew most strongly on glucose/fructose and were partially or completely inhibited by NaCl. The results showed that a universal isolation medium for xerophilic fungi could be based on glycerol or glucose/fructose but not on NaCl as aw-limiting solute.", "contents": "Influence of solute and hydrogen ion concentration on the water relations of some xerophilic fungi. Germination and growth of six xerophilic fungi, Aspergillus flavus, Aspergillus ochraceus, Eurotium chevalieri, Chrysosphorium fastidium, Wallemia sebi and Xeromyces bisporus were examined on media of a wide range of water activities (aw). The influence of three solutes, NaCl, glycerol and a glucose/fructose mixture, was studied at pH 4-0 and pH 6-5 using a plate-slide technique. Germination times and growth rates were affected by solute type, but the influence of pH was less marked. Except for Wallemia sebi, the fungi grew most strongly on glucose/fructose and were partially or completely inhibited by NaCl. The results showed that a universal isolation medium for xerophilic fungi could be based on glycerol or glucose/fructose but not on NaCl as aw-limiting solute."}
{"id": "PMID:19567", "title": "Effect of dietary threonine supplementation on tyrosine toxicity in the rat.", "content": "The objective of this study was to determine the effect of threonine supplementation on tyrosine metabolism in rats fed a low protein diet with excess tyrosine. The growth retardation and the development of eye and paw lesions that occur in rats ingesting a basal plus 3% or 5% L-tyrosine diet could be alleviated partially by the addition of 0.5% or 1.0% L-threonine to the diet. An increased blood tyrosine level in rats fed excess tyrosine was also lowered by threonine supplementation. In tyrotoxic conditions, the activities of liver tyrosine transaminase (EC 2.6.1.5) and threonine dehydratase (EC 4.2.9.16) were elevated, but p-hydroxyphenyl pyruvic acid oxidase (EC 1.13.11.27) which is also intimately associated with tyrosine toxicity was found to be inactivated. Furthermore, biosynthesis of ascorbic acid in liver was significantly lowered in this condition. However, addition of L-threonine in the diet, not only could cure the signs developed due to excess tyrosine, but also could affect the levels of enzymes studied.", "contents": "Effect of dietary threonine supplementation on tyrosine toxicity in the rat. The objective of this study was to determine the effect of threonine supplementation on tyrosine metabolism in rats fed a low protein diet with excess tyrosine. The growth retardation and the development of eye and paw lesions that occur in rats ingesting a basal plus 3% or 5% L-tyrosine diet could be alleviated partially by the addition of 0.5% or 1.0% L-threonine to the diet. An increased blood tyrosine level in rats fed excess tyrosine was also lowered by threonine supplementation. In tyrotoxic conditions, the activities of liver tyrosine transaminase (EC 2.6.1.5) and threonine dehydratase (EC 4.2.9.16) were elevated, but p-hydroxyphenyl pyruvic acid oxidase (EC 1.13.11.27) which is also intimately associated with tyrosine toxicity was found to be inactivated. Furthermore, biosynthesis of ascorbic acid in liver was significantly lowered in this condition. However, addition of L-threonine in the diet, not only could cure the signs developed due to excess tyrosine, but also could affect the levels of enzymes studied."}
{"id": "PMID:19568", "title": "Decreased opsonization for Streptococcus pneumoniae in sickle cell disease: studies on selected complement components and immunoglobulins.", "content": "Opsonic activity for Streptococcus pneumoniae in the sera of patients with sickle cell disease was reduced in comparison to the opsonic activity of sera from age-matched normal children. No difference in opsonic activity for Escherichi coli was observed in the sera from patients or normals. Total hemolytic complement, conversion of C3 by inulin and cobra venom factor, and levels of C3, factor B, properdin, C3b inactivator, and immunoglobulins G, A, and M were normal in patients' sera. The opsonic abnormality for S. pneumoniae was attributed to a deficiency of serum proteins rather than to an inhibitor of opsonic function. The data suggest that decreased opsonization was not associated with a deficiency of those complement components or immunoglobulins measured in this study.", "contents": "Decreased opsonization for Streptococcus pneumoniae in sickle cell disease: studies on selected complement components and immunoglobulins. Opsonic activity for Streptococcus pneumoniae in the sera of patients with sickle cell disease was reduced in comparison to the opsonic activity of sera from age-matched normal children. No difference in opsonic activity for Escherichi coli was observed in the sera from patients or normals. Total hemolytic complement, conversion of C3 by inulin and cobra venom factor, and levels of C3, factor B, properdin, C3b inactivator, and immunoglobulins G, A, and M were normal in patients' sera. The opsonic abnormality for S. pneumoniae was attributed to a deficiency of serum proteins rather than to an inhibitor of opsonic function. The data suggest that decreased opsonization was not associated with a deficiency of those complement components or immunoglobulins measured in this study."}
{"id": "PMID:19569", "title": "Methylmalonic aciduria: a variant form of methylmalonyl coenzyme A apomutase deficiency.", "content": "Sisters aged 3 and 4 1/2 years, respectively, who had grown and developed normally were found to have methylmalonic aciduria. The elder had had only one previous illness, at 18 months, and was thriving at six years without treatment; she was excreting up to 2 gm methylmalonic acid per day. The younger sister died during her third episode of illness, at 3 years of age. Studies of cultured skin fibroblasts showed deficient methylmalonyl coenzyme A mutase apoenzyme activity; cobalamin metabolism was normal. There was a moderate response in cultured cells to large amounts of added hydroxycobalamin; but treatment of the patient with high doses of intramuscular vitamin B12 for ten days failed to lower the urinary excretion of methylmalonic acid.", "contents": "Methylmalonic aciduria: a variant form of methylmalonyl coenzyme A apomutase deficiency. Sisters aged 3 and 4 1/2 years, respectively, who had grown and developed normally were found to have methylmalonic aciduria. The elder had had only one previous illness, at 18 months, and was thriving at six years without treatment; she was excreting up to 2 gm methylmalonic acid per day. The younger sister died during her third episode of illness, at 3 years of age. Studies of cultured skin fibroblasts showed deficient methylmalonyl coenzyme A mutase apoenzyme activity; cobalamin metabolism was normal. There was a moderate response in cultured cells to large amounts of added hydroxycobalamin; but treatment of the patient with high doses of intramuscular vitamin B12 for ten days failed to lower the urinary excretion of methylmalonic acid."}
{"id": "PMID:19571", "title": "Bilateral retractile testes--subsequent effects on fertility.", "content": "A group of 43 adults who as children had been diagnosed as having bilateral retractile testes were traced. Seventy-four per cent of the married patients had children. The testicular volume was normal in all the 19 patients examined.", "contents": "Bilateral retractile testes--subsequent effects on fertility. A group of 43 adults who as children had been diagnosed as having bilateral retractile testes were traced. Seventy-four per cent of the married patients had children. The testicular volume was normal in all the 19 patients examined."}
{"id": "PMID:19572", "title": "Fetal and maternal blood glucose, insulin and acid base observations following maternal glucose infusion.", "content": "The aim of the present investigation was to examine the fetal and maternal blood glucose and insulin response following glucose infusion to the mother. The studies were performed on 11 primigravid patients with a gestational age of 38-40 weeks during the first stage of labor. Glucose was given intravenously by a bolus injection of 330 mg/kg body weight, followed by a glucose infusion of 27.5 mg/kg/min for 60 min. Glucose concentration, immuno-reactive insulin (IRI), pH and base excess of the maternal and fetal blood were measured before and during maternal glucose load. Maternal blood glucose rose within 10 min. up to 280.0 mg% (SD 25.9). This level could be fairly maintained throughout the experiment. The maternal glucose was after 60 min. infusion 326.5 mg% (SD 46.9). Fetal glucose concentration rose continuously from 65.8 mg% (SD 5.8) at control to 249.2 mg% (SD 23.3) after 60 min. The increase of maternal and fetal glucose was associated with an elevation of immuno-reactive insulin (IRI). The maternal insulin was 24.0 micronU/ml (SD 8.0). It was scattered over a wide range (55.4 micronU/ml-217.1 micronU/ml) after 60 min. glucose infusion. The fetal insulin was 17.0 micronU/ml (SD 5.2) at control and rose by 86.5% (SD 80.5) after 60 min. glucose load. One case of a mother with a subclinical diabetes mellitus deviated where the fetal insulin rose from 26.0 micronU/ml at control to 215.6 micronU/ml after 60 min. infusion. The increase of insulin per glucose rise was correlated to fetal body weight. During glucose infusion to the mother of both, fetal and maternal, acid base parameters remained unchanged. From these observations it may be concluded that in the human fetus insulin secretion following a single glucose load is generally low, however, it increases in cases where the maternal insulin response to glucose load is abnormal. This might be related to a chronic stimulation by glucose of the fetal pancreatic islet cells in poorly controlled diabetic and possibly prediabetic patients.", "contents": "Fetal and maternal blood glucose, insulin and acid base observations following maternal glucose infusion. The aim of the present investigation was to examine the fetal and maternal blood glucose and insulin response following glucose infusion to the mother. The studies were performed on 11 primigravid patients with a gestational age of 38-40 weeks during the first stage of labor. Glucose was given intravenously by a bolus injection of 330 mg/kg body weight, followed by a glucose infusion of 27.5 mg/kg/min for 60 min. Glucose concentration, immuno-reactive insulin (IRI), pH and base excess of the maternal and fetal blood were measured before and during maternal glucose load. Maternal blood glucose rose within 10 min. up to 280.0 mg% (SD 25.9). This level could be fairly maintained throughout the experiment. The maternal glucose was after 60 min. infusion 326.5 mg% (SD 46.9). Fetal glucose concentration rose continuously from 65.8 mg% (SD 5.8) at control to 249.2 mg% (SD 23.3) after 60 min. The increase of maternal and fetal glucose was associated with an elevation of immuno-reactive insulin (IRI). The maternal insulin was 24.0 micronU/ml (SD 8.0). It was scattered over a wide range (55.4 micronU/ml-217.1 micronU/ml) after 60 min. glucose infusion. The fetal insulin was 17.0 micronU/ml (SD 5.2) at control and rose by 86.5% (SD 80.5) after 60 min. glucose load. One case of a mother with a subclinical diabetes mellitus deviated where the fetal insulin rose from 26.0 micronU/ml at control to 215.6 micronU/ml after 60 min. infusion. The increase of insulin per glucose rise was correlated to fetal body weight. During glucose infusion to the mother of both, fetal and maternal, acid base parameters remained unchanged. From these observations it may be concluded that in the human fetus insulin secretion following a single glucose load is generally low, however, it increases in cases where the maternal insulin response to glucose load is abnormal. This might be related to a chronic stimulation by glucose of the fetal pancreatic islet cells in poorly controlled diabetic and possibly prediabetic patients."}
{"id": "PMID:19574", "title": "The effect of temperature on the tensile strength and disintegration of paracetamol and oxytetracycline tablets.", "content": "The tensile strengths and disintegration times of paracetamol and oxytetracycline tablets at room temperature are higher when they have been prepared at high temperatures, e.g. 85 degrees, than at room temperature or below, e.g.--20 degrees. The activation energies of the two materials, 3 and 1 k cal mol-1 (13 and 4kJmol-1) respectively, were derived from plots of log tensile strength and log disintegration time versus the reciprocal of the absolute temperature. The results have been explained in terms of sintering theory and the formation of welded bonds between particles.", "contents": "The effect of temperature on the tensile strength and disintegration of paracetamol and oxytetracycline tablets. The tensile strengths and disintegration times of paracetamol and oxytetracycline tablets at room temperature are higher when they have been prepared at high temperatures, e.g. 85 degrees, than at room temperature or below, e.g.--20 degrees. The activation energies of the two materials, 3 and 1 k cal mol-1 (13 and 4kJmol-1) respectively, were derived from plots of log tensile strength and log disintegration time versus the reciprocal of the absolute temperature. The results have been explained in terms of sintering theory and the formation of welded bonds between particles."}
{"id": "PMID:19575", "title": "Binder distribution onto binary mixtures of glass spheres.", "content": "Glass spheres (0-8 and 0-4 cm diam.) in differing weight ratios were treated in a rotating pan with four pharmaceutical binder fluids. Binder uptake for a sphere of 1 g was greater onto the smaller spheres irrespective of binder or wt ratio used. There were differences in uniformity of uptake, the solution binders (PVP and gelatin) being more evenly distributed than the mucilaginous binders (starch and methylcellulose). Binder distribution on the basis of unit surface area showed less obvious differences between the sphere sizes. Possible consequences of such binder distribution through powder aggregates are discussed.", "contents": "Binder distribution onto binary mixtures of glass spheres. Glass spheres (0-8 and 0-4 cm diam.) in differing weight ratios were treated in a rotating pan with four pharmaceutical binder fluids. Binder uptake for a sphere of 1 g was greater onto the smaller spheres irrespective of binder or wt ratio used. There were differences in uniformity of uptake, the solution binders (PVP and gelatin) being more evenly distributed than the mucilaginous binders (starch and methylcellulose). Binder distribution on the basis of unit surface area showed less obvious differences between the sphere sizes. Possible consequences of such binder distribution through powder aggregates are discussed."}
{"id": "PMID:19576", "title": "Permeation of oestrone, oestradiol, oestriol and dexamethasone across cellulose acetate membrane.", "content": "The permeation across cellulose acetate of three oestrogens, differing only in the number of hydroxyl groups attached to the nucleus, and a 'standard' steroid, dexamethasone, was investigated using the lag-time method for calculating diffusion parameters, between 10 and 40 degrees. Diffusion coefficients for the similarly-sized oestrogens were relatively insensitive to marked changes in polarity, but increased permeation was correlated with increased partition coefficients, decreased polarity and fewer hydroxyl groups on the nucleus. Permeation increased with temperature and energies of activation were calculated from Arrhenius-type plots. Ep values ranged from 4-84 k cal mol-1 (20 kJ mol-1) for the least polar steroid (oestrone) to 6-91 k cal mol-1 (29 kJ mol-1) for the most polar steroid (oestriol). The results implied that steroid diffusion occurred through aqueous membrane channels, but that it was impeded to various extents by both obstruction and polar interaction effects.", "contents": "Permeation of oestrone, oestradiol, oestriol and dexamethasone across cellulose acetate membrane. The permeation across cellulose acetate of three oestrogens, differing only in the number of hydroxyl groups attached to the nucleus, and a 'standard' steroid, dexamethasone, was investigated using the lag-time method for calculating diffusion parameters, between 10 and 40 degrees. Diffusion coefficients for the similarly-sized oestrogens were relatively insensitive to marked changes in polarity, but increased permeation was correlated with increased partition coefficients, decreased polarity and fewer hydroxyl groups on the nucleus. Permeation increased with temperature and energies of activation were calculated from Arrhenius-type plots. Ep values ranged from 4-84 k cal mol-1 (20 kJ mol-1) for the least polar steroid (oestrone) to 6-91 k cal mol-1 (29 kJ mol-1) for the most polar steroid (oestriol). The results implied that steroid diffusion occurred through aqueous membrane channels, but that it was impeded to various extents by both obstruction and polar interaction effects."}
{"id": "PMID:19577", "title": "Effect of a second solubilizate on the partition coefficient of drugs in micellar solution and their permeation rate across an artificial membrane.", "content": "The distribution of a solubilizate between micelles and the aqueous phase does not obey a simple partition law when a second solubilizate species is present. Alterations of the apparent partition coefficient cannot be explained in terms of a simple displacement mechanism, following the interaction of both solubilizates with the same site of the micelle. A non linear increase in solubilizate association to micelles following an increase in surfactant concentration is observed in the presence of a second solubilizate. A depression in the cloud point temperature follows the addition of a second species and is such that cannot be interpreted as a simple additive effect. Alteration of the apparent partition coefficient in a miscellar solution has an effect on the permeation rate of the solubilizate across an artificial membrane. Biopharmaceutical implications are discussed.", "contents": "Effect of a second solubilizate on the partition coefficient of drugs in micellar solution and their permeation rate across an artificial membrane. The distribution of a solubilizate between micelles and the aqueous phase does not obey a simple partition law when a second solubilizate species is present. Alterations of the apparent partition coefficient cannot be explained in terms of a simple displacement mechanism, following the interaction of both solubilizates with the same site of the micelle. A non linear increase in solubilizate association to micelles following an increase in surfactant concentration is observed in the presence of a second solubilizate. A depression in the cloud point temperature follows the addition of a second species and is such that cannot be interpreted as a simple additive effect. Alteration of the apparent partition coefficient in a miscellar solution has an effect on the permeation rate of the solubilizate across an artificial membrane. Biopharmaceutical implications are discussed."}
{"id": "PMID:19578", "title": "The release of plasticizer from polyvinyl chloride haemodialysis tubing.", "content": "The extent of migration of plasticizer from haemodialysis lines into saline and plasma has been examined and a number of different types of tubing have been compared. A model system designed to simulate in vivo haemodialysis was evolved. The method uses a continuous cyclohexane extraction in order to mimic uptake of plasticizer by body tissues. Although not an ideal system, the results obtained are indicative of the extent to which the plasticizers are leached.", "contents": "The release of plasticizer from polyvinyl chloride haemodialysis tubing. The extent of migration of plasticizer from haemodialysis lines into saline and plasma has been examined and a number of different types of tubing have been compared. A model system designed to simulate in vivo haemodialysis was evolved. The method uses a continuous cyclohexane extraction in order to mimic uptake of plasticizer by body tissues. Although not an ideal system, the results obtained are indicative of the extent to which the plasticizers are leached."}
{"id": "PMID:19579", "title": "The effect of tris buffers on rat liver mitochondrial monoamine oxidase.", "content": "The effect of tris buffers upon the monoamine oxidase (MAO) activity in rat liver mitochondria has been investigated. Tris buffer was shown to inhibit MAO in a non-competitive manner with a Ki of 15-25 mM. Tyramine, 5-hydroxytryptamine and beta-phenethylamine but not benzylamine oxidations were all inhibited by tris buffer. All inhibitions, except that of 5-HT, were completely reversible. It is suggested that these effects are produced by conformational changes in the structure of the MAO. The significance of these results is discussed with respect to the use of tris buffers in the extraction and estimation of the activity of MAO.", "contents": "The effect of tris buffers on rat liver mitochondrial monoamine oxidase. The effect of tris buffers upon the monoamine oxidase (MAO) activity in rat liver mitochondria has been investigated. Tris buffer was shown to inhibit MAO in a non-competitive manner with a Ki of 15-25 mM. Tyramine, 5-hydroxytryptamine and beta-phenethylamine but not benzylamine oxidations were all inhibited by tris buffer. All inhibitions, except that of 5-HT, were completely reversible. It is suggested that these effects are produced by conformational changes in the structure of the MAO. The significance of these results is discussed with respect to the use of tris buffers in the extraction and estimation of the activity of MAO."}
{"id": "PMID:19580", "title": "Metabolic oxidation of aralkyl oximes to nitro compounds by fortified 9000g liver supernatants from various species.", "content": "Incubation of 'amphetamine oxime' (IIa, anti-benzyl methyl ketoxime) with fortified rabbit liver 9000 g supernatants gave the nitro compound (Ie) and the beta-hydroxylated oxime (IIc) in addition to the previously reported ketone (IIb) and alcohol (Ic) metabolites. Formation of the products was cofactor dependent. The nitro compound was also formed using mouse, hamster and guinea-pig 9000 g liver supernatants and to a minor extent by rat liver. The oximes of 2-phenethylamine (IIe) and norfenfluramine (IIg) were also metabolized to the corresponding nitro compounds, ketones and alcohols with rabbit 9000 g liver supernatants; however, no nitro compound (IIIb) was detected after the incubation of 'mexiletine oxime' (IVa). The metabolic products were identified and characterized by g.l.c., t.l.c. and g.l.c. linked mass spectrometry by comparison with synthetic materials.", "contents": "Metabolic oxidation of aralkyl oximes to nitro compounds by fortified 9000g liver supernatants from various species. Incubation of 'amphetamine oxime' (IIa, anti-benzyl methyl ketoxime) with fortified rabbit liver 9000 g supernatants gave the nitro compound (Ie) and the beta-hydroxylated oxime (IIc) in addition to the previously reported ketone (IIb) and alcohol (Ic) metabolites. Formation of the products was cofactor dependent. The nitro compound was also formed using mouse, hamster and guinea-pig 9000 g liver supernatants and to a minor extent by rat liver. The oximes of 2-phenethylamine (IIe) and norfenfluramine (IIg) were also metabolized to the corresponding nitro compounds, ketones and alcohols with rabbit 9000 g liver supernatants; however, no nitro compound (IIIb) was detected after the incubation of 'mexiletine oxime' (IVa). The metabolic products were identified and characterized by g.l.c., t.l.c. and g.l.c. linked mass spectrometry by comparison with synthetic materials."}
{"id": "PMID:19581", "title": "Dopamine receptors in rat striatum and nucleus accumbens; conformational studies using rigid analogues of dopamine.", "content": "A study was made of the actions of dopamine and of some 2-amino-1,2,3,4-tetrahydronaphthalenes on dopamine-sensitive adenylate cyclase in homogenates of rat striatum and nucleus accumbens. The compounds were also tested for their ability to stimulate motor activity following bilateral injection into the nucleus accumbens of conscious rats. The most active compounds on adenylate cyclase from both striatum and nucleus accumbens were dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene(6,7-diOHATN). The 5,6-dihydroxy analogue (5,6-diOHATN) was 50 times less active than 6,7-diOHATN in striatal homogenates and 350 times less active in homogenates of nucleus accumbens. All dihydroxy compounds tested were active in causing stimulation of motor activity, the most active compounds being 6,7-and5,6diOHATN. Both dimethoxy derivatives tested were inactive on the adenylate cyclase and as locomotor stimulants.", "contents": "Dopamine receptors in rat striatum and nucleus accumbens; conformational studies using rigid analogues of dopamine. A study was made of the actions of dopamine and of some 2-amino-1,2,3,4-tetrahydronaphthalenes on dopamine-sensitive adenylate cyclase in homogenates of rat striatum and nucleus accumbens. The compounds were also tested for their ability to stimulate motor activity following bilateral injection into the nucleus accumbens of conscious rats. The most active compounds on adenylate cyclase from both striatum and nucleus accumbens were dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene(6,7-diOHATN). The 5,6-dihydroxy analogue (5,6-diOHATN) was 50 times less active than 6,7-diOHATN in striatal homogenates and 350 times less active in homogenates of nucleus accumbens. All dihydroxy compounds tested were active in causing stimulation of motor activity, the most active compounds being 6,7-and5,6diOHATN. Both dimethoxy derivatives tested were inactive on the adenylate cyclase and as locomotor stimulants."}
{"id": "PMID:19582", "title": "The effects of diethylcarbamazine citrate on smooth muscle.", "content": "The effect of the anthelmintic drug diethylcarbamazine citrate (DECC) was examined on the guinea-pig isolated ileum, rabbit duodenum, chick oesophagus, rat portal vein and pig coronary artery. DECC contracted all the gastrointestinal smooth muscle preparations. The contractions were antagonized by hexamethonium and atropine but they were not affected by mepyramine or methysergide in concentrations that abolished, or markedly reduced, responses to histamine and 5-hydroxytryptamine. DECC inhibited the responses of the guinea-pig ileum to other spasmogens, namely, acetylcholine, histamine and nicotine. Physostigmine markedly potentiated the responses of the chick oesophagus and the rabbit duodenum to DECC. DECC relaxed the potassium chloride-induced contractions of the pig coronary artery strips; these relaxations were not modified by propranolol or calcium chloride. There was no evidence that DECC released histamine from skin or muscle.", "contents": "The effects of diethylcarbamazine citrate on smooth muscle. The effect of the anthelmintic drug diethylcarbamazine citrate (DECC) was examined on the guinea-pig isolated ileum, rabbit duodenum, chick oesophagus, rat portal vein and pig coronary artery. DECC contracted all the gastrointestinal smooth muscle preparations. The contractions were antagonized by hexamethonium and atropine but they were not affected by mepyramine or methysergide in concentrations that abolished, or markedly reduced, responses to histamine and 5-hydroxytryptamine. DECC inhibited the responses of the guinea-pig ileum to other spasmogens, namely, acetylcholine, histamine and nicotine. Physostigmine markedly potentiated the responses of the chick oesophagus and the rabbit duodenum to DECC. DECC relaxed the potassium chloride-induced contractions of the pig coronary artery strips; these relaxations were not modified by propranolol or calcium chloride. There was no evidence that DECC released histamine from skin or muscle."}
{"id": "PMID:19592", "title": "Interpretation of dissolution rate data from in vitro testing of compressed tablets.", "content": "To find if theoretically and experimentally a relation existed between the dissolution rate theory of Kitazawa, Johno & others (1975) and that of Wagner (1969), a study was undertaken with uncoated caffeine, aspirin and proxyphylline tablets using two dissolution methods. Although the original treatment for surface area of drug available for dissolution was quite different between the two dissolution theories, the dissolution rate constants obtained were in fair agreement. Hence it might not be always necessary to take into consideration changes in the surface area as a function of dissolution rate, and the 1n W infinity/(W infinity) versus time plot devised by Kitazawa & others might be a useful and simple means of obtaining the dissolution rate constant of an active ingredient from a dosage form such as compressed tablet.", "contents": "Interpretation of dissolution rate data from in vitro testing of compressed tablets. To find if theoretically and experimentally a relation existed between the dissolution rate theory of Kitazawa, Johno & others (1975) and that of Wagner (1969), a study was undertaken with uncoated caffeine, aspirin and proxyphylline tablets using two dissolution methods. Although the original treatment for surface area of drug available for dissolution was quite different between the two dissolution theories, the dissolution rate constants obtained were in fair agreement. Hence it might not be always necessary to take into consideration changes in the surface area as a function of dissolution rate, and the 1n W infinity/(W infinity) versus time plot devised by Kitazawa & others might be a useful and simple means of obtaining the dissolution rate constant of an active ingredient from a dosage form such as compressed tablet."}
{"id": "PMID:19593", "title": "The extraction and analysis of benzodiazepines in tissues by enzymic digestion and high-performance liquid chromatography.", "content": "A simple, rapid and sensitive method is described for the analysis of unchanged benzodiazepine drugs and their metabolites, in human and animal tissues, using the proteolytic enzyme subtilisin Carlsberg followed by reverse-phase liquid chromatography. The enzymic digestion yields far higher recoveries than conventional extraction methods, while the liquid chromatogrpahic analysis allows the rapid separation and detection of nanogram quantities of these drugs without the need for elaborate \"clean-up\" procedures.", "contents": "The extraction and analysis of benzodiazepines in tissues by enzymic digestion and high-performance liquid chromatography. A simple, rapid and sensitive method is described for the analysis of unchanged benzodiazepine drugs and their metabolites, in human and animal tissues, using the proteolytic enzyme subtilisin Carlsberg followed by reverse-phase liquid chromatography. The enzymic digestion yields far higher recoveries than conventional extraction methods, while the liquid chromatogrpahic analysis allows the rapid separation and detection of nanogram quantities of these drugs without the need for elaborate \"clean-up\" procedures."}
{"id": "PMID:19594", "title": "Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats.", "content": "Amphetamine-like stimulants were divided into two groups, one in which the stereotyped behaviour was not antagonized by reserpine [(+)-amphetamine, (-)-amphetamine, methamphetamine, phenmetrazine and phenethylamine] and another group in which the behavioural effects were blocked by reserpine (methylphenidate, nomifensine, pipradrol and amfonelic acid (NCA; Win 25978)). Both groups increased homovanillic acid (HVA) in whole brain 2 h after administration. The 'methylphenidate group' also increased brain 3,4-dihydroxyphenylacetic acid (DOPAC) in naive rats; whereas the '(+)-amphetamine group' decreased DOPAC in naive rats, as well as in reserpinized rats, alpha-methyl-p-tyrosine-treated rats and after acute hemisection. The reserpine antagonism of the 'methylphenidate group'-induced stereotyped behaviour was partially reversed by type A monoamine oxidase inhibition. The '(+)-amphetamine group'-induced stereotyped behaviour was not blocked by short time pretreatment with alpha-methyltyrosine, only by longer pretreatment intervals. The mechanisms by which the two groups are differentiated biochemically is discussed with special attention to possible intra-neuronal inhibition of dopamine oxidation by the '(+)-amphetamine group'.", "contents": "Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats. Amphetamine-like stimulants were divided into two groups, one in which the stereotyped behaviour was not antagonized by reserpine [(+)-amphetamine, (-)-amphetamine, methamphetamine, phenmetrazine and phenethylamine] and another group in which the behavioural effects were blocked by reserpine (methylphenidate, nomifensine, pipradrol and amfonelic acid (NCA; Win 25978)). Both groups increased homovanillic acid (HVA) in whole brain 2 h after administration. The 'methylphenidate group' also increased brain 3,4-dihydroxyphenylacetic acid (DOPAC) in naive rats; whereas the '(+)-amphetamine group' decreased DOPAC in naive rats, as well as in reserpinized rats, alpha-methyl-p-tyrosine-treated rats and after acute hemisection. The reserpine antagonism of the 'methylphenidate group'-induced stereotyped behaviour was partially reversed by type A monoamine oxidase inhibition. The '(+)-amphetamine group'-induced stereotyped behaviour was not blocked by short time pretreatment with alpha-methyltyrosine, only by longer pretreatment intervals. The mechanisms by which the two groups are differentiated biochemically is discussed with special attention to possible intra-neuronal inhibition of dopamine oxidation by the '(+)-amphetamine group'."}
{"id": "PMID:19595", "title": "Neurochemical correlates of ethanol withdrawal: alterations in serotoninergic function.", "content": "Cessation of chronic ethanol administration, and elimination of ethanol from the body, results in a withdrawal syndrome in mice characterized by behavioural symptoms and hypothermia. During withdrawal, the accumulation rate of [14C] 5-hydroxytryptamine (5-HT) from [14C]tryptophan, was significantly lower in the brainstem of the ethanol-withdrawn animals than in controls. A similar pattern was seen in forebrain. When the rate of 5-HT accumulation was determined using pargyline, no differences occurred between control and ethanol-treated animals. The endogenous concentrations of tryptophan in plasma, and tryptophan, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain were the same in ethanol-treated and control animals. It is suggested that the changes in accumulation of 14C-5-HT and 14C-5-HIAA in ethanol-withdrawn animals reflected alterations in electrical activity of serotoninergic neurons during withdrawal.", "contents": "Neurochemical correlates of ethanol withdrawal: alterations in serotoninergic function. Cessation of chronic ethanol administration, and elimination of ethanol from the body, results in a withdrawal syndrome in mice characterized by behavioural symptoms and hypothermia. During withdrawal, the accumulation rate of [14C] 5-hydroxytryptamine (5-HT) from [14C]tryptophan, was significantly lower in the brainstem of the ethanol-withdrawn animals than in controls. A similar pattern was seen in forebrain. When the rate of 5-HT accumulation was determined using pargyline, no differences occurred between control and ethanol-treated animals. The endogenous concentrations of tryptophan in plasma, and tryptophan, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain were the same in ethanol-treated and control animals. It is suggested that the changes in accumulation of 14C-5-HT and 14C-5-HIAA in ethanol-withdrawn animals reflected alterations in electrical activity of serotoninergic neurons during withdrawal."}
{"id": "PMID:19597", "title": "Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver.", "content": "In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.", "contents": "Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver. In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction."}
{"id": "PMID:19598", "title": "Neutral in vivo metabolites of cannabinol isolated from rat faeces.", "content": "The in vivo transformation of cannabinol (CBN) in the rat has been studied. Unchanged CBN and nine neutral mono-oxygenated and dioxygenated CBN metabolites have been identified. In the mono-oxygenated series the metabolites occurred in decreasing order of prominence as follows: 7-hydroxy-CBN, 4''-hydroxy-CBN, 1''-hydroxy-CBN, 2''-hydroxy-CBN, 3''-hydroxy-CBN, 5''-hydroxy-CBN and CBN-7-al. In the dihydroxylated metabolite series only 1'',7-dihydroxy-CBN and 4'',7-dihydroxy-CBN were found with the former as the more prominent metabolite.", "contents": "Neutral in vivo metabolites of cannabinol isolated from rat faeces. The in vivo transformation of cannabinol (CBN) in the rat has been studied. Unchanged CBN and nine neutral mono-oxygenated and dioxygenated CBN metabolites have been identified. In the mono-oxygenated series the metabolites occurred in decreasing order of prominence as follows: 7-hydroxy-CBN, 4''-hydroxy-CBN, 1''-hydroxy-CBN, 2''-hydroxy-CBN, 3''-hydroxy-CBN, 5''-hydroxy-CBN and CBN-7-al. In the dihydroxylated metabolite series only 1'',7-dihydroxy-CBN and 4'',7-dihydroxy-CBN were found with the former as the more prominent metabolite."}
{"id": "PMID:19599", "title": "Cannabinoid patterns in seedlings of Cannabis sativa L. and their use in the determination of chemical race.", "content": "We have examined the cannabinoid contents of seedlings from twelve strains of Cannabis of known chemical race. Fourteen days after emergence of the shoot those of the tetrahydrocannabinol (THC) type could be distinguished from those of the cannabidiol (CBD) type. The true leaves of the THC type contained a relatively high content of THC and also contained cannabichromene (CBC), sometimes as the major cannabinoid, whereas the CBD type had much lower amounts of THC and no CBC; CBD being the major component. A strain from China corresponded to the THC type but showed some unusual features. Seeds purchased at seven outlets in Britain were also examined. Only two batches germinated by these proved to be of a THC type and resembled the Chinese strain.", "contents": "Cannabinoid patterns in seedlings of Cannabis sativa L. and their use in the determination of chemical race. We have examined the cannabinoid contents of seedlings from twelve strains of Cannabis of known chemical race. Fourteen days after emergence of the shoot those of the tetrahydrocannabinol (THC) type could be distinguished from those of the cannabidiol (CBD) type. The true leaves of the THC type contained a relatively high content of THC and also contained cannabichromene (CBC), sometimes as the major cannabinoid, whereas the CBD type had much lower amounts of THC and no CBC; CBD being the major component. A strain from China corresponded to the THC type but showed some unusual features. Seeds purchased at seven outlets in Britain were also examined. Only two batches germinated by these proved to be of a THC type and resembled the Chinese strain."}
{"id": "PMID:19612", "title": "Degradation of carmustine in aqueous media.", "content": "The degradation rate of carmustine was investigated in buffered aqueous media at several pH values. The buffering agents studied were those with potential use in parenteral formulations of this drug: acetate, citrate, and phosphate. The apparent first-order degradation rate constants were calculated using a linear regression procedure. A pH range over which minimum degradation occurred was ascertained. General acid and specific base catalysis was demonstrated for the degradation of carmustine. From the data at 5, 22, and 37 degrees, the apparent activation energies for carmustine degradation in buffered aqueous media were computed and were strongly pH dependent.", "contents": "Degradation of carmustine in aqueous media. The degradation rate of carmustine was investigated in buffered aqueous media at several pH values. The buffering agents studied were those with potential use in parenteral formulations of this drug: acetate, citrate, and phosphate. The apparent first-order degradation rate constants were calculated using a linear regression procedure. A pH range over which minimum degradation occurred was ascertained. General acid and specific base catalysis was demonstrated for the degradation of carmustine. From the data at 5, 22, and 37 degrees, the apparent activation energies for carmustine degradation in buffered aqueous media were computed and were strongly pH dependent."}
{"id": "PMID:19613", "title": "Spectrophotometric determination of cephapirin, a cephalosporin antibacterial.", "content": "A simple and specific method for the quantitative determination of cephapirin, a cephalosporin antibacterial, in finished bulk and dosage forms is reported. The method is based on reproducible degradation under controlled conditions to an unidentified species, which is measured spectrophotometrically at 375 nm. The procedure can be performed manually on a short series of samples in about 15 min or can be automated for large runs. Precursors and related substances show minimal interference. The coefficient of variation of the automated system is about 1% within days and 1.3% among days.", "contents": "Spectrophotometric determination of cephapirin, a cephalosporin antibacterial. A simple and specific method for the quantitative determination of cephapirin, a cephalosporin antibacterial, in finished bulk and dosage forms is reported. The method is based on reproducible degradation under controlled conditions to an unidentified species, which is measured spectrophotometrically at 375 nm. The procedure can be performed manually on a short series of samples in about 15 min or can be automated for large runs. Precursors and related substances show minimal interference. The coefficient of variation of the automated system is about 1% within days and 1.3% among days."}
{"id": "PMID:19614", "title": "High-pressure liquid chromatographic analysis of cimetidine, a histamine H2-receptor antagonist, in blood and urine.", "content": "A method is described for extraction of cimetidine, a histamine H2-receptor antagonist, from whole blood and urine with subsequent analysis by high-pressure liquid chromatography (HPLC). The drug is extracted from biological fluids with 1-octanol and back-extracted into dilute acid and then into a small volume of ethanol by saturation with potassium carbonate. HPLC analysis is performed on a column of 5-micrometer silica with a mixed mobile phase consisting primarily of acetonitrile. The method measures concentrations of cimetidine as low as 0.05 microgram/ml and is reproducible. Blood levels and urinary excretion data obtained with the analytical procedure are given for a group of human subjects who received 200-mg oral doses of cimetidine.", "contents": "High-pressure liquid chromatographic analysis of cimetidine, a histamine H2-receptor antagonist, in blood and urine. A method is described for extraction of cimetidine, a histamine H2-receptor antagonist, from whole blood and urine with subsequent analysis by high-pressure liquid chromatography (HPLC). The drug is extracted from biological fluids with 1-octanol and back-extracted into dilute acid and then into a small volume of ethanol by saturation with potassium carbonate. HPLC analysis is performed on a column of 5-micrometer silica with a mixed mobile phase consisting primarily of acetonitrile. The method measures concentrations of cimetidine as low as 0.05 microgram/ml and is reproducible. Blood levels and urinary excretion data obtained with the analytical procedure are given for a group of human subjects who received 200-mg oral doses of cimetidine."}
{"id": "PMID:19615", "title": "Rate and proposed mechanism of anhydrotetracycline epimerization in acid solution.", "content": "The pathway through which the toxic tetracycline degradation product epianhydrotetracycline forms in solution was studied using high-performance liquid chromatography and circular dichroism, taking advantage of the large difference in ellipticity between the reactant and the product at 285 nm. The epimerization of anhydrotetracycline followed a reversible first-order process, and both analytical methods yielded the same rate constants. The rate constants indicate that anhydrotetracycline epimerization is faster than tetracycline epimerization. The equilibrium favored anhydrotetracycline, and the activation energies for the forward and reverse rates were almost the same as those for tetracycline epimerization. The epimerization was catalyzed by phosphate. Activation energies in 0.1 and 1 M phosphate were essentially the same. The equilibrium constants for both anhydrotetracycline and tetracycline favored the natural configuration rather than the epi series. Possible rationalization based on conformational and hydrogen bonding effects is presented.", "contents": "Rate and proposed mechanism of anhydrotetracycline epimerization in acid solution. The pathway through which the toxic tetracycline degradation product epianhydrotetracycline forms in solution was studied using high-performance liquid chromatography and circular dichroism, taking advantage of the large difference in ellipticity between the reactant and the product at 285 nm. The epimerization of anhydrotetracycline followed a reversible first-order process, and both analytical methods yielded the same rate constants. The rate constants indicate that anhydrotetracycline epimerization is faster than tetracycline epimerization. The equilibrium favored anhydrotetracycline, and the activation energies for the forward and reverse rates were almost the same as those for tetracycline epimerization. The epimerization was catalyzed by phosphate. Activation energies in 0.1 and 1 M phosphate were essentially the same. The equilibrium constants for both anhydrotetracycline and tetracycline favored the natural configuration rather than the epi series. Possible rationalization based on conformational and hydrogen bonding effects is presented."}
{"id": "PMID:19616", "title": "Fluorometric determination of nadolol in human serum and urine.", "content": "To determine nadolol, a new beta-adrenergic blocking agent, in serum and urine, the drug is extracted into n-butyl acetate or ether from alkaline potassium chloride saturated samples. After back-extraction into 0.1 N HCl, the drug is oxidized with periodic acid; the resulting aldehyde is coupled with o-phenylenediamine to produce a fluorescent compound. The method can measure as little as 0.01 microgram of nadolol/sample.", "contents": "Fluorometric determination of nadolol in human serum and urine. To determine nadolol, a new beta-adrenergic blocking agent, in serum and urine, the drug is extracted into n-butyl acetate or ether from alkaline potassium chloride saturated samples. After back-extraction into 0.1 N HCl, the drug is oxidized with periodic acid; the resulting aldehyde is coupled with o-phenylenediamine to produce a fluorescent compound. The method can measure as little as 0.01 microgram of nadolol/sample."}
{"id": "PMID:19617", "title": "Degradation kinetics of a substituted carbinolamine in aqueous media.", "content": "The apparent first-order breakdown of the medicinally active agent 3-(p-chlorophenyl)-2-ethyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-3-ol was studied in aqueous solutions where dehydration gave the unsaturated compound 3-(p-chlorophenyl)-5,6-dihydro-2-ethylimidazo[2,1-b]thiazole. This thiazole was the primary solvolytic product produced in approximately quantitative yields for the temperature range studied and ostensibly underwent no further reaction in acidic media even on prolonged heating. Investigations were carried out at various pH values in standard buffers at constant ionic strength. The ionization constants of the compounds are reported as well as the apparent activation energies for the degradation in acid and acetate buffers. The influence of ionic strength on the velocity constant was determined.", "contents": "Degradation kinetics of a substituted carbinolamine in aqueous media. The apparent first-order breakdown of the medicinally active agent 3-(p-chlorophenyl)-2-ethyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-3-ol was studied in aqueous solutions where dehydration gave the unsaturated compound 3-(p-chlorophenyl)-5,6-dihydro-2-ethylimidazo[2,1-b]thiazole. This thiazole was the primary solvolytic product produced in approximately quantitative yields for the temperature range studied and ostensibly underwent no further reaction in acidic media even on prolonged heating. Investigations were carried out at various pH values in standard buffers at constant ionic strength. The ionization constants of the compounds are reported as well as the apparent activation energies for the degradation in acid and acetate buffers. The influence of ionic strength on the velocity constant was determined."}
{"id": "PMID:19620", "title": "An in vivo assay for the analysis of the biological potency and structure-activity relationships of narcotics: serum testosterone depletion in the male rat.", "content": "An in vivo method for the assessment of the agonistic-antagonistic activities and structure-activity relationships of the narcotics is described. The method, which is based on the depletion of serum testosterone levels by the narcotics in the male, satisfies all of the criteria necessary for a valid narcotic assay: 1) The ability of the narcotics to deplete serum testosterone levels is stereospecific; 2) naloxone competitively inhibits their effects; 3) and the relative potencies of the drugs in depressing serum testosterone levels parallels their activity in inhibiting electrically induced contractions of the guinea-pig ileum, the binding of [3H]opiates to \"receptors\" in rat brain homogenates and their relative effectiveness as analgesics. Although only rats were used in the current studies, the method can be easily adapted for use in any species, including man.", "contents": "An in vivo assay for the analysis of the biological potency and structure-activity relationships of narcotics: serum testosterone depletion in the male rat. An in vivo method for the assessment of the agonistic-antagonistic activities and structure-activity relationships of the narcotics is described. The method, which is based on the depletion of serum testosterone levels by the narcotics in the male, satisfies all of the criteria necessary for a valid narcotic assay: 1) The ability of the narcotics to deplete serum testosterone levels is stereospecific; 2) naloxone competitively inhibits their effects; 3) and the relative potencies of the drugs in depressing serum testosterone levels parallels their activity in inhibiting electrically induced contractions of the guinea-pig ileum, the binding of [3H]opiates to \"receptors\" in rat brain homogenates and their relative effectiveness as analgesics. Although only rats were used in the current studies, the method can be easily adapted for use in any species, including man."}
{"id": "PMID:19621", "title": "Direct and beta adrenergic blocking actions of nadolol (SQ 11725) on electrophysiologic properties of isolated canine myocardium.", "content": "Effects of nadolol, a new beta adrenergic antagonist, were determined on transmembrane potentials of canine Purkinje fibers and ventricular and atrial muscle. Significant alterations in Purkinje fiber potentials occurred only with nadolol concentrations of 10(-4) M or greater. After 1 hour exposure to 10(-4) M, resting potential and action potential amplitude were reduced; at 3 hours, action potential rate of rise, phase 2 duration and action potential duration at 75% repolarization also were decreased. 10(-3) M nadolol also was depressant and, additionally, consistently reduced membrane responsiveness. Nadolol (10(-8)-10(-4) M) had no significant effects on effective refractory period. Ventricular and atrial muscle were less sensitive to all drug concentrations. Nadolol (10(-8)-10(-4) M) had little action on automaticity in normal, ouabain-treated or stretched Purkinje fibers but markedly decreased catecholamine-enhanced automaticity. In isoproterenol-treated Purkinje fibers, pA2 for nadolol was 8.2 and 7.7 for propranolol. Nadolol (10(-3) M or less) did not affect isometric force developed by isolated canine atrial trabeculae. We suggest that direct membrane depressant effects of nadolol do not contribute to its antiarrhythmic activity and that its beta adrenergic blocking ability is beneficial in catecholamine-related cardiac ectopia.", "contents": "Direct and beta adrenergic blocking actions of nadolol (SQ 11725) on electrophysiologic properties of isolated canine myocardium. Effects of nadolol, a new beta adrenergic antagonist, were determined on transmembrane potentials of canine Purkinje fibers and ventricular and atrial muscle. Significant alterations in Purkinje fiber potentials occurred only with nadolol concentrations of 10(-4) M or greater. After 1 hour exposure to 10(-4) M, resting potential and action potential amplitude were reduced; at 3 hours, action potential rate of rise, phase 2 duration and action potential duration at 75% repolarization also were decreased. 10(-3) M nadolol also was depressant and, additionally, consistently reduced membrane responsiveness. Nadolol (10(-8)-10(-4) M) had no significant effects on effective refractory period. Ventricular and atrial muscle were less sensitive to all drug concentrations. Nadolol (10(-8)-10(-4) M) had little action on automaticity in normal, ouabain-treated or stretched Purkinje fibers but markedly decreased catecholamine-enhanced automaticity. In isoproterenol-treated Purkinje fibers, pA2 for nadolol was 8.2 and 7.7 for propranolol. Nadolol (10(-3) M or less) did not affect isometric force developed by isolated canine atrial trabeculae. We suggest that direct membrane depressant effects of nadolol do not contribute to its antiarrhythmic activity and that its beta adrenergic blocking ability is beneficial in catecholamine-related cardiac ectopia."}
{"id": "PMID:19627", "title": "Synthesis and stereospecific antipsychotic activity of (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine.", "content": "The synthesis and resolution of 3-iodocyproheptadine [(+/-)-5a] and 1-cyclopropylmethyl-4-(3-iodo-5H-dibenzo-[a,d]cyclohepten-5-ylidene)piperidine [(+/-)-5b] are described. The resulting atropisomers undergo reaction with trifluoromethylthiocopper to give optically active products without extensive racemization. In this manner, optically pure (+)- and (-)-3-trifluoromethylthiocyproheptadine [(+)-6a and (-)-6a, respectively] and (+)- and (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine [(+)-6b and (-)-6b, respectively] have been prepared. The influence of a chiral europium shift reagent on the proton and fluorine resonance signals as a diagnostic tool for the determination of the optical purities of these atropisomers is discussed. The four compounds, (+)-6a, (-)-6a, (+)-6b, and (-)-6b, were studied in squirrel monkeys for their ability to block conditioned avoidance responding. All of the antiavoidance activity was found to reside solely in the levorotatory compounds (-)-6a and (-)-6b. Further comparison of the enantiomers (-)-6b and (+)-6b showed that the ability to antagonize apomorphine-induced stereotyped behavior is confined to the levorotatory isomer (-)-6b while weak central anticholinergic activity resides solely in the dextrorotatory isomer (+)-6b. Neither (-)-6b has significant peripheral anticholinergic activity.", "contents": "Synthesis and stereospecific antipsychotic activity of (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine. The synthesis and resolution of 3-iodocyproheptadine [(+/-)-5a] and 1-cyclopropylmethyl-4-(3-iodo-5H-dibenzo-[a,d]cyclohepten-5-ylidene)piperidine [(+/-)-5b] are described. The resulting atropisomers undergo reaction with trifluoromethylthiocopper to give optically active products without extensive racemization. In this manner, optically pure (+)- and (-)-3-trifluoromethylthiocyproheptadine [(+)-6a and (-)-6a, respectively] and (+)- and (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine [(+)-6b and (-)-6b, respectively] have been prepared. The influence of a chiral europium shift reagent on the proton and fluorine resonance signals as a diagnostic tool for the determination of the optical purities of these atropisomers is discussed. The four compounds, (+)-6a, (-)-6a, (+)-6b, and (-)-6b, were studied in squirrel monkeys for their ability to block conditioned avoidance responding. All of the antiavoidance activity was found to reside solely in the levorotatory compounds (-)-6a and (-)-6b. Further comparison of the enantiomers (-)-6b and (+)-6b showed that the ability to antagonize apomorphine-induced stereotyped behavior is confined to the levorotatory isomer (-)-6b while weak central anticholinergic activity resides solely in the dextrorotatory isomer (+)-6b. Neither (-)-6b has significant peripheral anticholinergic activity."}
{"id": "PMID:19628", "title": "An approach to peripheral vasodilator-beta-adrenergic blocking agents.", "content": "The syntheses of 2-phenyl- and 2-pyridyl-4-trifluoromethylimidazoles having a 3-tert-butylamino-2-hydroxypropoxy moiety attached to the aryl or heteroaryl substituent are described. Structure--activity relationships based on results from an evaluation of these compounds for antihypertensive, vasodilating, and beta-adrenergic blocking activities are discussed.", "contents": "An approach to peripheral vasodilator-beta-adrenergic blocking agents. The syntheses of 2-phenyl- and 2-pyridyl-4-trifluoromethylimidazoles having a 3-tert-butylamino-2-hydroxypropoxy moiety attached to the aryl or heteroaryl substituent are described. Structure--activity relationships based on results from an evaluation of these compounds for antihypertensive, vasodilating, and beta-adrenergic blocking activities are discussed."}
{"id": "PMID:19629", "title": "Adrenergic agents. 6. Synthesis and potential beta-adrenergic agonist activity of some meta-substituted p-hydroxyphenylethanolamines related to salbutamol.", "content": "Salbutamol, an adrenergic receptor agonist with selectivity for tracheobronchial vs. cardiac muscle, differs from the catecholamine N-tert-butylnorepinephrine in that it bears a hydroxymethyl, rather than a phenolic, group in the meta position. In a search for new bronchodilating agents with minimal cardiovascular side effects, a series of derivatives, in which this m-hydroxymethyl group is modified, was prepared. These compounds were examined for potential bronchodilator activity in an in vitro test that measures relaxation of guinea pig tracheal smooth muscle. Potential cardiac stimulant activity was evaluated in vitro by monitoring changes in the rate of contraction of spontaneously beating guinea pig right atria. Although many of these compounds retained a high degree of potency, all were less effective than salbutamol in the tracheal test. Several of the derivatives, notably ones bearing 1-hydroxyethyl (1d), 1,2-dihydroxyethyl (1f), 1-hydroxy-2-methoxyethyl (1g), and 2-hydroxy-1-methoxyethyl (1h) substituents in place of the parent's m-hydroxymethyl group, however, were considerably more selective for tracheobronchial vs. cardiac muscle in the in vitro tests utilizing guinea pig tracheal and right atrial muscle.", "contents": "Adrenergic agents. 6. Synthesis and potential beta-adrenergic agonist activity of some meta-substituted p-hydroxyphenylethanolamines related to salbutamol. Salbutamol, an adrenergic receptor agonist with selectivity for tracheobronchial vs. cardiac muscle, differs from the catecholamine N-tert-butylnorepinephrine in that it bears a hydroxymethyl, rather than a phenolic, group in the meta position. In a search for new bronchodilating agents with minimal cardiovascular side effects, a series of derivatives, in which this m-hydroxymethyl group is modified, was prepared. These compounds were examined for potential bronchodilator activity in an in vitro test that measures relaxation of guinea pig tracheal smooth muscle. Potential cardiac stimulant activity was evaluated in vitro by monitoring changes in the rate of contraction of spontaneously beating guinea pig right atria. Although many of these compounds retained a high degree of potency, all were less effective than salbutamol in the tracheal test. Several of the derivatives, notably ones bearing 1-hydroxyethyl (1d), 1,2-dihydroxyethyl (1f), 1-hydroxy-2-methoxyethyl (1g), and 2-hydroxy-1-methoxyethyl (1h) substituents in place of the parent's m-hydroxymethyl group, however, were considerably more selective for tracheobronchial vs. cardiac muscle in the in vitro tests utilizing guinea pig tracheal and right atrial muscle."}
{"id": "PMID:19630", "title": "Central nervous system activity of a novel class of annelated 1,4-benzodiazepines, aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-ones.", "content": "The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1,2-a][1,4]-benzodiazepin-1-one (10) led to the synthesis of a group of compounds with potent minor tranquillizer activity.", "contents": "Central nervous system activity of a novel class of annelated 1,4-benzodiazepines, aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-ones. The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1,2-a][1,4]-benzodiazepin-1-one (10) led to the synthesis of a group of compounds with potent minor tranquillizer activity."}
{"id": "PMID:19634", "title": "Congenital total hemihypertrophy and carcinoma of undescended testicle: a case report.", "content": "The first case of germinal cell tumor of the testis in a patient with congenital total hemihypertrophy is reported. The literature is discussed with emphasis placed on the frequent association of hemihypertrophy with oncogenesis and teratogenesis. We conclude that because of the high incidence of malignancy in the undescended testis prophylactic orchiectomy should be considered in a patient with hemihypertrophy and cryptorchidism.", "contents": "Congenital total hemihypertrophy and carcinoma of undescended testicle: a case report. The first case of germinal cell tumor of the testis in a patient with congenital total hemihypertrophy is reported. The literature is discussed with emphasis placed on the frequent association of hemihypertrophy with oncogenesis and teratogenesis. We conclude that because of the high incidence of malignancy in the undescended testis prophylactic orchiectomy should be considered in a patient with hemihypertrophy and cryptorchidism."}
{"id": "PMID:19635", "title": "Evaluation of cimetidine (tagamet). An antagonist of hydrochloric acid secretion.", "content": "Cimetidine, a potent H2-receptor antagonist, has been introduced for the treatment of various conditions associated with acid peptic digestion in the gastrointestinal tract. Preliminary results are encouraging. Adverse reactions do not appear to be substantial; however, the effect of long-term use has yet to be ascertained.", "contents": "Evaluation of cimetidine (tagamet). An antagonist of hydrochloric acid secretion. Cimetidine, a potent H2-receptor antagonist, has been introduced for the treatment of various conditions associated with acid peptic digestion in the gastrointestinal tract. Preliminary results are encouraging. Adverse reactions do not appear to be substantial; however, the effect of long-term use has yet to be ascertained."}
{"id": "PMID:19636", "title": "Neural blockade by local anesthetics.", "content": "Local anesthetics block nerve impulse propagation by occluding transmembrane sodium channels, so preventing depolarization. First, the uncharged lipid-soluble anesthetic base pentrates the membrane; then the positively charged cation binds to anionic components of the sodium channel's internal axoplasmic mouth. Though primarily a carrier, the base contributes to blockade by causing the membrane to swell, so pinching the sodium channels. Dissolved in water, local anesthetic salt crystals dissociate into anesthetic cation and base-proportional to the drug's fixed pKa and the tissue's variable pH. The cation-base concentration ration is critical to optimal neural blockade. If there is too little base, few anesthetic molecules will penetrate to the neural target; if too little cation, few sodium channels will be plugged.", "contents": "Neural blockade by local anesthetics. Local anesthetics block nerve impulse propagation by occluding transmembrane sodium channels, so preventing depolarization. First, the uncharged lipid-soluble anesthetic base pentrates the membrane; then the positively charged cation binds to anionic components of the sodium channel's internal axoplasmic mouth. Though primarily a carrier, the base contributes to blockade by causing the membrane to swell, so pinching the sodium channels. Dissolved in water, local anesthetic salt crystals dissociate into anesthetic cation and base-proportional to the drug's fixed pKa and the tissue's variable pH. The cation-base concentration ration is critical to optimal neural blockade. If there is too little base, few anesthetic molecules will penetrate to the neural target; if too little cation, few sodium channels will be plugged."}
{"id": "PMID:19637", "title": "Aspiration of metallic mercury. A 22-year follow-up.", "content": "Rupture of the mercury-filled bag of an intestinal tube resulted in aspiration of metallic mercury 22 years ago in the patient reported. Immediate respiratory distress was treated with vigorous suctioning and postural drainage. Follow-up chest roentgenograms persistently showed radiopaque particles in the lungs. Signs and symptoms of chronic respiratory disease have since developed in the patient. Postmortem findings from the lungs included globules of metallic mercury surrounded by extensive fibrosis and granuloma formation, which we believe to be the result of local irritative effects of mercury.", "contents": "Aspiration of metallic mercury. A 22-year follow-up. Rupture of the mercury-filled bag of an intestinal tube resulted in aspiration of metallic mercury 22 years ago in the patient reported. Immediate respiratory distress was treated with vigorous suctioning and postural drainage. Follow-up chest roentgenograms persistently showed radiopaque particles in the lungs. Signs and symptoms of chronic respiratory disease have since developed in the patient. Postmortem findings from the lungs included globules of metallic mercury surrounded by extensive fibrosis and granuloma formation, which we believe to be the result of local irritative effects of mercury."}
{"id": "PMID:19639", "title": "L-asparaginase--antileukemia agent.", "content": "This paper describes the most recent development in the field of biosynthesis of L-Asparaginase by means of various culture, purification by Column Chromatography, informations of the Catabolite repression of L-Asparaginase and its metabolism in mycobacteria. The separation, purification studies, idea about the effect of different PH on activity, quaternary structure and the effect of specific antibodies on catalytic activity of L-Asparaginase is discussed. This material shows the role of L-Asparaginase in acute lymphocytic leukemia.", "contents": "L-asparaginase--antileukemia agent. This paper describes the most recent development in the field of biosynthesis of L-Asparaginase by means of various culture, purification by Column Chromatography, informations of the Catabolite repression of L-Asparaginase and its metabolism in mycobacteria. The separation, purification studies, idea about the effect of different PH on activity, quaternary structure and the effect of specific antibodies on catalytic activity of L-Asparaginase is discussed. This material shows the role of L-Asparaginase in acute lymphocytic leukemia."}
{"id": "PMID:19642", "title": "Pathogenesis of vascular injury in rejecting rat renal allografts.", "content": "Unmodified rejection of rat renal allografts was characterized by the early onset and rapid progression of endothelial damage in venules and capillaries which culminated in ischemic cortical necrosis. This pattern of endothelial injury correlated with lymphocyte accumulation in vascular lumens and could not be duplicated by renal perfusion with alloantibodies or prevented by C'3 depletion. In contrast, endothelial integrity and normal graft function were maintained over study intervals extending to 200 days when Brown Norway (BN) rat kidneys were transplanted into Lewis (Le) rat kidney recipients subjected to neonatal thymectomy or lymph drainage. Vascular lesions occurred when syngeneic thoracic duct lymphocytes were transfused into these recipients, but irreversible endothelial injury could be prevented by simultaneous injections of immune plasma. These findings indicate that the destruction of donor endothelium is mediated by thymus-dependent immune mechanisms which can be altered by thoracic duct drainage to promote indefinite survival of renal allografts across major histocompatibility loci.", "contents": "Pathogenesis of vascular injury in rejecting rat renal allografts. Unmodified rejection of rat renal allografts was characterized by the early onset and rapid progression of endothelial damage in venules and capillaries which culminated in ischemic cortical necrosis. This pattern of endothelial injury correlated with lymphocyte accumulation in vascular lumens and could not be duplicated by renal perfusion with alloantibodies or prevented by C'3 depletion. In contrast, endothelial integrity and normal graft function were maintained over study intervals extending to 200 days when Brown Norway (BN) rat kidneys were transplanted into Lewis (Le) rat kidney recipients subjected to neonatal thymectomy or lymph drainage. Vascular lesions occurred when syngeneic thoracic duct lymphocytes were transfused into these recipients, but irreversible endothelial injury could be prevented by simultaneous injections of immune plasma. These findings indicate that the destruction of donor endothelium is mediated by thymus-dependent immune mechanisms which can be altered by thoracic duct drainage to promote indefinite survival of renal allografts across major histocompatibility loci."}
{"id": "PMID:19645", "title": "[Hemodynamic changes after angiotensin II blockade by saralasin (author's transl)].", "content": "Saralasin, an angiotensin II inhibitor was infused in 10 hypertensive patients. A blood pressure reduction was achieved after stimulation of the renin-angiotensin-system by salt depletion. Heart rate and cardiac output failed to compensate for reduction of blood pressure. Thus circulatory reflex-mechanisms are inhibited by saralasin. A direct influence on baroreceptor mechanism and/or catecholamines is probable. Failure of the hypotensive effect of saralasin in salt-depleted patients after administration of beta-blockers supports this hypothesis.", "contents": "[Hemodynamic changes after angiotensin II blockade by saralasin (author's transl)]. Saralasin, an angiotensin II inhibitor was infused in 10 hypertensive patients. A blood pressure reduction was achieved after stimulation of the renin-angiotensin-system by salt depletion. Heart rate and cardiac output failed to compensate for reduction of blood pressure. Thus circulatory reflex-mechanisms are inhibited by saralasin. A direct influence on baroreceptor mechanism and/or catecholamines is probable. Failure of the hypotensive effect of saralasin in salt-depleted patients after administration of beta-blockers supports this hypothesis."}
{"id": "PMID:19649", "title": "Fine structural changes in dog myocardium exposed to lowered pH in vivo.", "content": "A surgical preparation that allows chemical alteration of the blood supplied to specific area of the intact heart was used to investigate the effects of lowered tissue pH on the fine structure of myocardial cells. Controlled infusion of isotonic saline acidified with HCl to a pH value between 1.0 and 2.0 produced a lowering of blood pH to values of less than 7.0. This drop in the pH of the perfusing blood resulted in a corresponding decrease in pH of the relevant area of myocardium. When this decrease occurred without a concomitant increase in tissue lactate level, the myocardial cells of the acid-perfused area showed focal glycogen depletion, moderate relaxation of myofibrils and clumping of nuclear chromatin, and mild mitochondrial change, which did not include marked swelling although intramitochondrial electron-dense inclusions were often detectable. When the fall in pH was accompanied by a large increase in lactate concentration, however, the cells showed more severe glycogen depletion and clumping of nuclear chromatin, and mitochondrial change, which did include marked swelling, together with the presence of well developed inclusions.", "contents": "Fine structural changes in dog myocardium exposed to lowered pH in vivo. A surgical preparation that allows chemical alteration of the blood supplied to specific area of the intact heart was used to investigate the effects of lowered tissue pH on the fine structure of myocardial cells. Controlled infusion of isotonic saline acidified with HCl to a pH value between 1.0 and 2.0 produced a lowering of blood pH to values of less than 7.0. This drop in the pH of the perfusing blood resulted in a corresponding decrease in pH of the relevant area of myocardium. When this decrease occurred without a concomitant increase in tissue lactate level, the myocardial cells of the acid-perfused area showed focal glycogen depletion, moderate relaxation of myofibrils and clumping of nuclear chromatin, and mild mitochondrial change, which did not include marked swelling although intramitochondrial electron-dense inclusions were often detectable. When the fall in pH was accompanied by a large increase in lactate concentration, however, the cells showed more severe glycogen depletion and clumping of nuclear chromatin, and mitochondrial change, which did include marked swelling, together with the presence of well developed inclusions."}
{"id": "PMID:19653", "title": "Metal complexes of poly(alpha-amino acids). A potentiometric and circular dichroism investigation of Cu(II) complexes of poly(L-lysine), poly(L-ornithine), and poly(L-diaminobutyric acid).", "content": "The conformational properties of cupric complexes of poly(L-lysine), poly(L-ornithine), and poly(L-diaminobutyric acid) have been investigated by potentiometric, visible and UV absorption, and circular dichroism (CD) techniques. The three polymers form two kinds of complexes stable at pH less than 8.5 (type I complexes) and at pH less than 8.5 (type II complexes). It has been found that in the low pH complexes of poly(L-diaminobutyric acid) at least one deprotonated amido nitrogen is coordinated to cupric ions. Type II complexes involve always amide nitrogens in the coordination sphere of Cu(II). Evidence is presented that the structure of such complexes is not compatible with the alpha-helical conformation of the peptide backbone.", "contents": "Metal complexes of poly(alpha-amino acids). A potentiometric and circular dichroism investigation of Cu(II) complexes of poly(L-lysine), poly(L-ornithine), and poly(L-diaminobutyric acid). The conformational properties of cupric complexes of poly(L-lysine), poly(L-ornithine), and poly(L-diaminobutyric acid) have been investigated by potentiometric, visible and UV absorption, and circular dichroism (CD) techniques. The three polymers form two kinds of complexes stable at pH less than 8.5 (type I complexes) and at pH less than 8.5 (type II complexes). It has been found that in the low pH complexes of poly(L-diaminobutyric acid) at least one deprotonated amido nitrogen is coordinated to cupric ions. Type II complexes involve always amide nitrogens in the coordination sphere of Cu(II). Evidence is presented that the structure of such complexes is not compatible with the alpha-helical conformation of the peptide backbone."}
{"id": "PMID:19659", "title": "The microbiology of chronic middle ear effusions in children.", "content": "Serous otitis media is the most common cause of hearing loss in childhood. Traditionally, this entity has been felt to be a sterile process. This study was undertaken to determine the incidence of infected middle ear fluid in patients with asymptomatic middle ear effusions. The external auditory canal, nasopharynx and middle ear fluids of 57 patients undergoing myringotomy were cultured. Of 57 patients, 26 had positive cultures; 67% of patients less than 36 months of age had positive culture, with a bacterial flora closely resembling that of acute otitis media. Further investigation is required to determine the significance of such infection together with the optimum therapy for chronic effusions of the middle ear in young children.", "contents": "The microbiology of chronic middle ear effusions in children. Serous otitis media is the most common cause of hearing loss in childhood. Traditionally, this entity has been felt to be a sterile process. This study was undertaken to determine the incidence of infected middle ear fluid in patients with asymptomatic middle ear effusions. The external auditory canal, nasopharynx and middle ear fluids of 57 patients undergoing myringotomy were cultured. Of 57 patients, 26 had positive cultures; 67% of patients less than 36 months of age had positive culture, with a bacterial flora closely resembling that of acute otitis media. Further investigation is required to determine the significance of such infection together with the optimum therapy for chronic effusions of the middle ear in young children."}
{"id": "PMID:19666", "title": "[Pathogenesis of hepatic encephalopathy (author's transl)].", "content": "This contribution presents data from the literature as well as our own results concerning the mechanisms of hepatic encephalopathy (HE). 1. Blood chemistry: In patients with liver cirrhosis, the plasma levels of ammonia, phenylalanine, tyrosine, phenolic acids, and octopamine correlated with the stages of HE. Methionine and free tryptophan concentrations were increased only in stages 2-4. Further, branched chain amino acids were below the normal range. Experimental findings in animals elucidated some mechanisms of these changes. 2. Effects of administered substances: With ammonia, methionine, methanethiol, tryptophan, phenolic substances, and fatty acids central nervous disturbances were observed. 3. Interactions: Anemia, methanethiol, and fatty acids favored ammonia toxicity. Alkalosis diminished cerebral symptoms. 4. Neurotransmitters: HE was accompanied by an enhanced turnover of serotonin and by increased amounts of false neurotransmitters (like octopamine) in the brain. 5. Oxydative brain metabolism: Disorders of cerebral oxygen and glucose utilization were mainly documented in cases of long term HE with EEG alterations. 6. Structural changes of the brain: Most of them are irreversible.", "contents": "[Pathogenesis of hepatic encephalopathy (author's transl)]. This contribution presents data from the literature as well as our own results concerning the mechanisms of hepatic encephalopathy (HE). 1. Blood chemistry: In patients with liver cirrhosis, the plasma levels of ammonia, phenylalanine, tyrosine, phenolic acids, and octopamine correlated with the stages of HE. Methionine and free tryptophan concentrations were increased only in stages 2-4. Further, branched chain amino acids were below the normal range. Experimental findings in animals elucidated some mechanisms of these changes. 2. Effects of administered substances: With ammonia, methionine, methanethiol, tryptophan, phenolic substances, and fatty acids central nervous disturbances were observed. 3. Interactions: Anemia, methanethiol, and fatty acids favored ammonia toxicity. Alkalosis diminished cerebral symptoms. 4. Neurotransmitters: HE was accompanied by an enhanced turnover of serotonin and by increased amounts of false neurotransmitters (like octopamine) in the brain. 5. Oxydative brain metabolism: Disorders of cerebral oxygen and glucose utilization were mainly documented in cases of long term HE with EEG alterations. 6. Structural changes of the brain: Most of them are irreversible."}
{"id": "PMID:19672", "title": "Effects of cyanide on peanut lipoxygenase.", "content": "Acidic and alkaline lipoxygenase isozymes were separated and assayed for activity while incubated in the presence of various concentrations of cyanide. Inhibition due to cyanide per se was not found. Instead, cyanide caused an increase in pH, which decreased the activity of the acidic isozyme to a rate corresponding to the same pH on the activity curve for the cyanide-free reaction.", "contents": "Effects of cyanide on peanut lipoxygenase. Acidic and alkaline lipoxygenase isozymes were separated and assayed for activity while incubated in the presence of various concentrations of cyanide. Inhibition due to cyanide per se was not found. Instead, cyanide caused an increase in pH, which decreased the activity of the acidic isozyme to a rate corresponding to the same pH on the activity curve for the cyanide-free reaction."}
{"id": "PMID:19671", "title": "Alkaloids of papaver genus IX. Alkaloids of Glaucium vitellinum Boiss and Buhse, population Seerjan and Glaucium pulchrum Stapf, population Elika.", "content": "Glaucium vitellinum Boiss and Buhse. population Seerjan was shown to contain three major alkaloids, isocorydine (0.44%), protopine (0.42%), dicentrine (0.24%), and four minor alkaloids, tetrahydropalmatine (0.13%), muramine (0.12%), bulbocapnine (0.06%) and glaucine (0.01%). Glaucium pulchrum Stapf popllation Elika was shown to contain two major alkaloids, corydine (0.3%) and bulbocapnine (0.18%) and three minor alkaloids N-methylindcarpine (0.1%), isocorydine (0.03%) and protopine (0.01%). N-methyllindcarpine was found for the first time in the Papaveraceae and tetrahydropalmatine was detected for the first time in Glaucium.", "contents": "Alkaloids of papaver genus IX. Alkaloids of Glaucium vitellinum Boiss and Buhse, population Seerjan and Glaucium pulchrum Stapf, population Elika. Glaucium vitellinum Boiss and Buhse. population Seerjan was shown to contain three major alkaloids, isocorydine (0.44%), protopine (0.42%), dicentrine (0.24%), and four minor alkaloids, tetrahydropalmatine (0.13%), muramine (0.12%), bulbocapnine (0.06%) and glaucine (0.01%). Glaucium pulchrum Stapf popllation Elika was shown to contain two major alkaloids, corydine (0.3%) and bulbocapnine (0.18%) and three minor alkaloids N-methylindcarpine (0.1%), isocorydine (0.03%) and protopine (0.01%). N-methyllindcarpine was found for the first time in the Papaveraceae and tetrahydropalmatine was detected for the first time in Glaucium."}
{"id": "PMID:19681", "title": "Simple assay for the condensation component enzyme (beta-ketoacyl synthetase) of fatty acid synthetase.", "content": "A simple assay is described for estimating the activity of the condensation component enzyme (beta-ketoacyl synthetase) of the yeast fatty acids synthetase complex. The radioactivity liberated as 14CO2 from [1,3-14C]malonyl-CoA was trapped in phenethylamine and measured by liquid scintillation spectroscopy. Three enzyme-catalysed steps are involved: acetyl-CoA transacylase, malonyl-CoA transacylase and beta-ketoacyl synthetase; however, beta-ketoacyl synthetase is rate-limiting. beta-Ketoacyl synthetase activity was made independent of subsequent enzyme activities of the complex by excluding NADPH from the assay, thus blocking beta-ketoacyl reductase and preventing fatty acid synthesis. By this assay beta-ketoacyl synthetase activity was about 0.28 of the activity of the complex for fatty acid synthesis, compared with approximately 0.001 for published assays. Several pyridine nucleotides and derivatives were tested after it was discovered that NADH stimulated beta-ketoacyl synthetase activity to a greater extent than could be accounted for by its reactivity in providing a pathway from acetoacetyl-enzyme to fatty acid synthesis. Presumably, the release of acetoacetate from the central sulphydryl of the complex is the rate-limiting step in the assay procedure.", "contents": "Simple assay for the condensation component enzyme (beta-ketoacyl synthetase) of fatty acid synthetase. A simple assay is described for estimating the activity of the condensation component enzyme (beta-ketoacyl synthetase) of the yeast fatty acids synthetase complex. The radioactivity liberated as 14CO2 from [1,3-14C]malonyl-CoA was trapped in phenethylamine and measured by liquid scintillation spectroscopy. Three enzyme-catalysed steps are involved: acetyl-CoA transacylase, malonyl-CoA transacylase and beta-ketoacyl synthetase; however, beta-ketoacyl synthetase is rate-limiting. beta-Ketoacyl synthetase activity was made independent of subsequent enzyme activities of the complex by excluding NADPH from the assay, thus blocking beta-ketoacyl reductase and preventing fatty acid synthesis. By this assay beta-ketoacyl synthetase activity was about 0.28 of the activity of the complex for fatty acid synthesis, compared with approximately 0.001 for published assays. Several pyridine nucleotides and derivatives were tested after it was discovered that NADH stimulated beta-ketoacyl synthetase activity to a greater extent than could be accounted for by its reactivity in providing a pathway from acetoacetyl-enzyme to fatty acid synthesis. Presumably, the release of acetoacetate from the central sulphydryl of the complex is the rate-limiting step in the assay procedure."}
{"id": "PMID:19682", "title": "Effects of various acids and salts on growth and aflatoxin production by Aspergillus flavus NRRL 3145.", "content": "The effects of sodium chloride, sodium acetate, benzoic acid, sodium benzoate, malonic acid, and sodium malonate on growth and aflatoxin production by Aspergillus flavus were investigated in synthetic media. Sodium chloride at concentrations equivalent to or greater than 12 g/100 ml inhibited growth and aflatoxin production, while at 8 g or less/100 ml, growth and aflatoxin production were stimulated. At 2 g or less/100 ml, sodium acetate also stimulated growth and aflatoxin production, but reduction occurred with 4 g or more/100 ml. Malonic acid at 10, 20, 40, and 50 mM reduced growth and aflatoxin production (over 50%) while sodium malonate at similar concentrations but different pH values had the opposite effect. Benzoic acid (pH 3.9) and sodium benzoate (pH 5.0) at 0.4 g/100 ml completely inhibited growth and aflatoxin production. Examination of the effect of initial pH indicated that the extent of inhibitory action of malonic acid and sodium acetate was a function of initial pH. The inhibitory action of benzoic acid and sodium benzoate appeared to be a function of undissociated benzoic acid molecules. Aflatoxin reduction was usually accompanied by an unidentified orange pigment, while aflatoxin stimulation was accompanied by unidentified blue and green fluorescent spots but with lower Rf values that aflatoxins B1, G1, B2, and G2 standards.", "contents": "Effects of various acids and salts on growth and aflatoxin production by Aspergillus flavus NRRL 3145. The effects of sodium chloride, sodium acetate, benzoic acid, sodium benzoate, malonic acid, and sodium malonate on growth and aflatoxin production by Aspergillus flavus were investigated in synthetic media. Sodium chloride at concentrations equivalent to or greater than 12 g/100 ml inhibited growth and aflatoxin production, while at 8 g or less/100 ml, growth and aflatoxin production were stimulated. At 2 g or less/100 ml, sodium acetate also stimulated growth and aflatoxin production, but reduction occurred with 4 g or more/100 ml. Malonic acid at 10, 20, 40, and 50 mM reduced growth and aflatoxin production (over 50%) while sodium malonate at similar concentrations but different pH values had the opposite effect. Benzoic acid (pH 3.9) and sodium benzoate (pH 5.0) at 0.4 g/100 ml completely inhibited growth and aflatoxin production. Examination of the effect of initial pH indicated that the extent of inhibitory action of malonic acid and sodium acetate was a function of initial pH. The inhibitory action of benzoic acid and sodium benzoate appeared to be a function of undissociated benzoic acid molecules. Aflatoxin reduction was usually accompanied by an unidentified orange pigment, while aflatoxin stimulation was accompanied by unidentified blue and green fluorescent spots but with lower Rf values that aflatoxins B1, G1, B2, and G2 standards."}
{"id": "PMID:19684", "title": "[Constitutive synthesis of cellulase by Trichoderma lignorum].", "content": "The induction of cellulase synthesis by lactose was studied in the resting cells of Trichoderma lignorum OM 534. The effect depended on the concentration of lactose, pH, and the age of the mycelium. The induction of the enzyme synthesis by lactose is supressed by glucose and its metabolites. The repression by glucose is partly eliminated by Cyk 3'-5'-AMP, theophylline, and coffeine. The induction of cellulase by lactose is regarded as a derepression of the synthesis of this enzyme as a result of slow assimilation of the disaccharide. The synthesis of cellulase in T. lignorum is presumed to be constitutive.", "contents": "[Constitutive synthesis of cellulase by Trichoderma lignorum]. The induction of cellulase synthesis by lactose was studied in the resting cells of Trichoderma lignorum OM 534. The effect depended on the concentration of lactose, pH, and the age of the mycelium. The induction of the enzyme synthesis by lactose is supressed by glucose and its metabolites. The repression by glucose is partly eliminated by Cyk 3'-5'-AMP, theophylline, and coffeine. The induction of cellulase by lactose is regarded as a derepression of the synthesis of this enzyme as a result of slow assimilation of the disaccharide. The synthesis of cellulase in T. lignorum is presumed to be constitutive."}
{"id": "PMID:19685", "title": "[Characteristics of a new cyanophage lysing unicellular cyanobacteria of the genus Synechococcus].", "content": "A new cyanophage S-2L growing on three strains of the cyanobacterium belonging to the Synechococcus genus has been isolated. The cyanophage has an icosahedral head, 56 nm in diameter, and flexible tail with a non-contracting sheath, 120 nm long. Over 95 per cent of the cyanophage particles are adsorbed within 10 min, the rate constant of adsorption being 3.2-10(-9) ml/min. The latent period lasts 5 hours, the yield is 100 particles per cell. The intracellular growth is characterized by the accumulation of the cyanophage particles at the poles of the cell. The photosynthetic lamellae remain intact up to the beginning of lysis which consists in local disruptions of the cell envelope.", "contents": "[Characteristics of a new cyanophage lysing unicellular cyanobacteria of the genus Synechococcus]. A new cyanophage S-2L growing on three strains of the cyanobacterium belonging to the Synechococcus genus has been isolated. The cyanophage has an icosahedral head, 56 nm in diameter, and flexible tail with a non-contracting sheath, 120 nm long. Over 95 per cent of the cyanophage particles are adsorbed within 10 min, the rate constant of adsorption being 3.2-10(-9) ml/min. The latent period lasts 5 hours, the yield is 100 particles per cell. The intracellular growth is characterized by the accumulation of the cyanophage particles at the poles of the cell. The photosynthetic lamellae remain intact up to the beginning of lysis which consists in local disruptions of the cell envelope."}
{"id": "PMID:19686", "title": "[Chemical composition of cells of a chemostatic culture of Bacillus megaterium during exposure to an alkaline pH value].", "content": "The culture of Bacillus megaterium was grown under chemostat conditions at a rate of 0.2, 0.4 and 0.7 hr-1, the growth being limited by a low content of citrate, and at alkaline pH values. Critical pH values were obtained for each growth rate: 9.6, 9.2 and 7.6, respectively. The content of protein decreased at alkaline pH, while the synthesis of total lipids, poly-beta-hydroxybutric acid and phospholipids was stimulated. Some changes were found in the ratio between polyphosphates of high molecular weight.", "contents": "[Chemical composition of cells of a chemostatic culture of Bacillus megaterium during exposure to an alkaline pH value]. The culture of Bacillus megaterium was grown under chemostat conditions at a rate of 0.2, 0.4 and 0.7 hr-1, the growth being limited by a low content of citrate, and at alkaline pH values. Critical pH values were obtained for each growth rate: 9.6, 9.2 and 7.6, respectively. The content of protein decreased at alkaline pH, while the synthesis of total lipids, poly-beta-hydroxybutric acid and phospholipids was stimulated. Some changes were found in the ratio between polyphosphates of high molecular weight."}
{"id": "PMID:19691", "title": "Syrup of ipecacuanha as an emetic in adults.", "content": "The emetic actions of syrup of ipecacuanha have been evaluated in 105 adult patients presenting at the emergency department of the Royal Perth Hospital with a diagnosis of accidental or intentional poisoning. The australian Pharmaceutical Formulary (APF) and the United States Pharmacopeia (USP) formulations of the syrup were compared and gave similar overall emetic responses of 88% and 89% respectively at a dose level of 15 ml. A 30 ml dose regimen of the APF formulation gave a slightly but not significantly increased overall emetic response of 96%. There were no differences between the three groups of patients in the time taken to vomit, the duration of vomiting or the volume of stomach contents recovered.", "contents": "Syrup of ipecacuanha as an emetic in adults. The emetic actions of syrup of ipecacuanha have been evaluated in 105 adult patients presenting at the emergency department of the Royal Perth Hospital with a diagnosis of accidental or intentional poisoning. The australian Pharmaceutical Formulary (APF) and the United States Pharmacopeia (USP) formulations of the syrup were compared and gave similar overall emetic responses of 88% and 89% respectively at a dose level of 15 ml. A 30 ml dose regimen of the APF formulation gave a slightly but not significantly increased overall emetic response of 96%. There were no differences between the three groups of patients in the time taken to vomit, the duration of vomiting or the volume of stomach contents recovered."}
{"id": "PMID:19688", "title": "Are the effects of psychomotor stimulant drugs on hyperactive children really paradoxical?", "content": "The improved \"attention\" exhibited by hyperactive children treated with amphetamine-like compounds is postulated to be related to a normal action of these drugs in producing stereotyped behavior. Such activity can be conceptualised as an increased \"focusing\" of attention, which would be expected to aid performance in tasks involving sustained concentration of attention, but impair performance on tasks involving reversals in cognitive strategy. These behavioural actions of the drugs can be linked to the functioning of central dopaminergic mechanisms.", "contents": "Are the effects of psychomotor stimulant drugs on hyperactive children really paradoxical? The improved \"attention\" exhibited by hyperactive children treated with amphetamine-like compounds is postulated to be related to a normal action of these drugs in producing stereotyped behavior. Such activity can be conceptualised as an increased \"focusing\" of attention, which would be expected to aid performance in tasks involving sustained concentration of attention, but impair performance on tasks involving reversals in cognitive strategy. These behavioural actions of the drugs can be linked to the functioning of central dopaminergic mechanisms."}
{"id": "PMID:19693", "title": "The firA gene, a locus involved in the expression of rifampicin resistance in Escherichia coli. II. Characterisation of bacterial proteins coded by lambdafirA transducing phages.", "content": "The firA gene probably codes for an essential component of the transcription machinery in E. coli. Bacterial proteins coded by lambdafirA transducing phages have been examined after infection of a UV-irradiated lambda lysogen, and 2 major fir-specific proteins have been characterized. The larger protein has a molecular weight of 27,000 daltons. The smaller protein, of 17,000 daltons, is produced in a considerable molar excess over the larger protein, is basic and binds strongly to DNA-, to DEAE- and to phospho-cellulose. This protein is clearly visible upon 2-dimensional gel electrophoresis of unfractionated E. coli protein, showing that it is present in the cell in large quantities. Evidence is presented to suggest that this protein may be identical to the Kappa factor of Sch\u00e4fer and Zillig (1973).", "contents": "The firA gene, a locus involved in the expression of rifampicin resistance in Escherichia coli. II. Characterisation of bacterial proteins coded by lambdafirA transducing phages. The firA gene probably codes for an essential component of the transcription machinery in E. coli. Bacterial proteins coded by lambdafirA transducing phages have been examined after infection of a UV-irradiated lambda lysogen, and 2 major fir-specific proteins have been characterized. The larger protein has a molecular weight of 27,000 daltons. The smaller protein, of 17,000 daltons, is produced in a considerable molar excess over the larger protein, is basic and binds strongly to DNA-, to DEAE- and to phospho-cellulose. This protein is clearly visible upon 2-dimensional gel electrophoresis of unfractionated E. coli protein, showing that it is present in the cell in large quantities. Evidence is presented to suggest that this protein may be identical to the Kappa factor of Sch\u00e4fer and Zillig (1973)."}
{"id": "PMID:19696", "title": "[Pyrivate kinase deficiency. II. Biochemical studies (author's transl)].", "content": "Pyruvate kinase deficiency was studied biochemically in ten homozygous and seven heterozygous individuals who previously had been examined clinically and hematologically (see part I). In crude hemolysates some properties of the deficient enzymes were found to be altered. The pH optimum was shifted towards the alkaline range, and the thermal optimum was found between 17 and 27 degrees Cinstead of between 37 und 47 degrees C. The abnormal enzymes were much less stable than normal pyruvate Kinase (PK), and more susceptible to inhibition by adenosinetriphosphate. The affinity to adenosinediphosphate was normal in all cases whereas the affinity to phosphoenolpyruvate was either normal (two cases/, increased (two cases) or slightly decreased (six cases). Fructosediphosphate activated the abnormal enzymes by a factor of 1.5--18 and simultaneously transformed the sigmoidal affinity curve with phosphoenolpyruvate into the hyperbolic curve known for the normal enzyme. The consumption of glucose and the formation of lactate were higher in PK deficient erythrocytes than in normal cells but lower than in erythrocyte populations with similar reticulocyte counts. The formation of 2,3-diphosphoglycerate was markedly increased, whereas its breakdown was low. A close relation between the degree of reticulocytosis and the impairment of glucose metabolism was found. In patients with high reticulocyte counts, i.e. in the splenectomized patients, the highest concentrations of glucose-6-phosphate, phosphoenolpyruvate, 3-phosphoglycerate and 2,3-diphosphoglycerate as well as a high formation and a low breakdown of 2,3-diphosphoglycerate and a deficit in lactate formation were found. In heterozygotes, small increases of the concentration of glucose-6-phosphate, phosphoenolpyruvate and 3-phosphoglycerate were demonstrated. Our results support the conclusion that PK deficiency is mainly a disorder of the reticulocytes. Their metabolism grossly deteriorates within the venous sinuses of the spleen. Splenectomy improves the clinical course because this critical area of microcirculation with a highly unfavourable metabolic milieu is eliminated.", "contents": "[Pyrivate kinase deficiency. II. Biochemical studies (author's transl)]. Pyruvate kinase deficiency was studied biochemically in ten homozygous and seven heterozygous individuals who previously had been examined clinically and hematologically (see part I). In crude hemolysates some properties of the deficient enzymes were found to be altered. The pH optimum was shifted towards the alkaline range, and the thermal optimum was found between 17 and 27 degrees Cinstead of between 37 und 47 degrees C. The abnormal enzymes were much less stable than normal pyruvate Kinase (PK), and more susceptible to inhibition by adenosinetriphosphate. The affinity to adenosinediphosphate was normal in all cases whereas the affinity to phosphoenolpyruvate was either normal (two cases/, increased (two cases) or slightly decreased (six cases). Fructosediphosphate activated the abnormal enzymes by a factor of 1.5--18 and simultaneously transformed the sigmoidal affinity curve with phosphoenolpyruvate into the hyperbolic curve known for the normal enzyme. The consumption of glucose and the formation of lactate were higher in PK deficient erythrocytes than in normal cells but lower than in erythrocyte populations with similar reticulocyte counts. The formation of 2,3-diphosphoglycerate was markedly increased, whereas its breakdown was low. A close relation between the degree of reticulocytosis and the impairment of glucose metabolism was found. In patients with high reticulocyte counts, i.e. in the splenectomized patients, the highest concentrations of glucose-6-phosphate, phosphoenolpyruvate, 3-phosphoglycerate and 2,3-diphosphoglycerate as well as a high formation and a low breakdown of 2,3-diphosphoglycerate and a deficit in lactate formation were found. In heterozygotes, small increases of the concentration of glucose-6-phosphate, phosphoenolpyruvate and 3-phosphoglycerate were demonstrated. Our results support the conclusion that PK deficiency is mainly a disorder of the reticulocytes. Their metabolism grossly deteriorates within the venous sinuses of the spleen. Splenectomy improves the clinical course because this critical area of microcirculation with a highly unfavourable metabolic milieu is eliminated."}
{"id": "PMID:19697", "title": "[Preoperative treatment of hyperthyroidism (author's transl)].", "content": "The preoperative preparation of hyperthyroidism requires the selective use of various drugs. As in the past, Plummer's iodine therapy takes precedence. Thyrostatics or beta receptor blockers, on the other hand, are only used in selected cases. The aim of preoperative preparation is euthyroidism. It is most rapidly and safely attained with Endoiodin (prolonium iodide) or combination of Endoiodine plus beta receptor blokkers. Thyrostatics appear to be less suitable for preparation, because they have a slow onset of action. Moreover, thyrostatics lead to densifications and adhesions of the thyroid gland capsule to the surrounding tissue, so that the preparation becomes complicated. 254 patients with hyperthyroidism and decompensated toxic adenoma were surgically treated without complications as a result of preparation with Endoiodin.", "contents": "[Preoperative treatment of hyperthyroidism (author's transl)]. The preoperative preparation of hyperthyroidism requires the selective use of various drugs. As in the past, Plummer's iodine therapy takes precedence. Thyrostatics or beta receptor blockers, on the other hand, are only used in selected cases. The aim of preoperative preparation is euthyroidism. It is most rapidly and safely attained with Endoiodin (prolonium iodide) or combination of Endoiodine plus beta receptor blokkers. Thyrostatics appear to be less suitable for preparation, because they have a slow onset of action. Moreover, thyrostatics lead to densifications and adhesions of the thyroid gland capsule to the surrounding tissue, so that the preparation becomes complicated. 254 patients with hyperthyroidism and decompensated toxic adenoma were surgically treated without complications as a result of preparation with Endoiodin."}
{"id": "PMID:19698", "title": "[Hypertension and anesthesia (author's transl)].", "content": "Five to six millions of hypertensives live in the Federal Republic of Germany. Of these, about 70% are known to be hypertensives but only 30% are consistently treated. It is therefore not surprising that hypertension is one of the most common risk factors in patients who have to be operatively treated. The commonly approved principles of hypertensive therapy are compiled in the present study and classified with reference to the multivarious pathophysiological processes. In particular, special anesthesiologic problems are dealt with in detail. Furthermore, this paper provides the basic knowledge of the artificial fall in blood pressure under anesthetic conditions.", "contents": "[Hypertension and anesthesia (author's transl)]. Five to six millions of hypertensives live in the Federal Republic of Germany. Of these, about 70% are known to be hypertensives but only 30% are consistently treated. It is therefore not surprising that hypertension is one of the most common risk factors in patients who have to be operatively treated. The commonly approved principles of hypertensive therapy are compiled in the present study and classified with reference to the multivarious pathophysiological processes. In particular, special anesthesiologic problems are dealt with in detail. Furthermore, this paper provides the basic knowledge of the artificial fall in blood pressure under anesthetic conditions."}
{"id": "PMID:19702", "title": "Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia.", "content": "To define the time course of the metabolic acidosis that follows a single grand-mal seizure, we obtained serial blood samples from eight consecutive patients. Immediately after a seizure, the mean (+/- S.E.M.) venous lactate concentration was 12.7 +/- 1.0 meq per liter, the mean carbon dioxide content 17.1 +/- 1.1 mmol per liter, and the mean arterial pH 7.14 +/- 0.06. Sixty minutes later their values were 6.6 +/- 0.7 meq per liter (P less than 0.005), 23.6 +/- 1.1 mmol per liter (P less than 0.005) and 7.38 +/- 0.04 (P less than 0.005) respectively. The spontaneous resolution of the acidosis was due, in large part, to the metabolism of lactate and to the concomitant removal of hydrogen ion. There was no change in the serum potassium concentration, despite the development of a severe systemic acidemia and the subsequent return to normal of the pH. We suggest that the patient with seizures may serve as a unique model of lactic acidosis.", "contents": "Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. To define the time course of the metabolic acidosis that follows a single grand-mal seizure, we obtained serial blood samples from eight consecutive patients. Immediately after a seizure, the mean (+/- S.E.M.) venous lactate concentration was 12.7 +/- 1.0 meq per liter, the mean carbon dioxide content 17.1 +/- 1.1 mmol per liter, and the mean arterial pH 7.14 +/- 0.06. Sixty minutes later their values were 6.6 +/- 0.7 meq per liter (P less than 0.005), 23.6 +/- 1.1 mmol per liter (P less than 0.005) and 7.38 +/- 0.04 (P less than 0.005) respectively. The spontaneous resolution of the acidosis was due, in large part, to the metabolism of lactate and to the concomitant removal of hydrogen ion. There was no change in the serum potassium concentration, despite the development of a severe systemic acidemia and the subsequent return to normal of the pH. We suggest that the patient with seizures may serve as a unique model of lactic acidosis."}
{"id": "PMID:19703", "title": "Drug impairment reviews: other drugs.", "content": "This review will summarize a limited number of experimental studies concerning effects of tranquilizers, muscle relaxants, and antihistamine drugs, as well as combinations of these drugs with ethanol, on human performance related to driving. The first group of studies utilized batteries of psychological and/or psychomotor tests to assess drug effects, while the second group used driving simulators. Procedures and results of each study will be summarized, and this will be followed by a general critique of methodologies which have been used along with suggestions for improved methodologies.", "contents": "Drug impairment reviews: other drugs. This review will summarize a limited number of experimental studies concerning effects of tranquilizers, muscle relaxants, and antihistamine drugs, as well as combinations of these drugs with ethanol, on human performance related to driving. The first group of studies utilized batteries of psychological and/or psychomotor tests to assess drug effects, while the second group used driving simulators. Procedures and results of each study will be summarized, and this will be followed by a general critique of methodologies which have been used along with suggestions for improved methodologies."}
{"id": "PMID:19712", "title": "Spontaneous hypoglycemia in end-stage renal failure.", "content": "Five men with end-stage renal failure had spontaneous hypoglycemia during lengthy hospitalizations. Four were cachectic, and all five had weight loss and poor caloric intake. Malnutrition were seen also in some of the ten previous case reports of hypoglycemia in renal failure. Impaired renal gluconeogenesis may allow hypoglycemia in such patients.", "contents": "Spontaneous hypoglycemia in end-stage renal failure. Five men with end-stage renal failure had spontaneous hypoglycemia during lengthy hospitalizations. Four were cachectic, and all five had weight loss and poor caloric intake. Malnutrition were seen also in some of the ten previous case reports of hypoglycemia in renal failure. Impaired renal gluconeogenesis may allow hypoglycemia in such patients."}
{"id": "PMID:19713", "title": "Pituitary responsiveness to LH-RH in intact and ovariectomized androgen-sterilized rats.", "content": "Serum LH changes in response to LH-RH injection were measured in intact and ovariectomized, steroid-treated female rats which were androgenized neonatally with 1,250 microgram testosterone propionate (TP) on day 5. At a dose of 20 ng LH-RH/100 g b.w., serum LH levels in intact rats increased over pre-injection levels, and at a dose of 100 ng LH-RH/100 g b.w., LH concentrations 15 min after injection were higher in nembutal-blocked proestrous rats than in androgen-sterilized rats. However, the ovulation response was not different between the groups. In ovariectomized estradiol benzoate (EB)-treated, androgen-sterilized rats, serum LH concentrations 15 and 60 min after LH-RH injection were lower than in similarly treated control rats. This effect was not secondary to the anovulatory state of the animal, since it also occurred in ovariectomized EB-treated prepuberal rats and in rats ovariectomized prepuberally and treated with EB in adulthood. Also, after treatment with 5alpha-dihydrotestosterone propionate (5alpha-DHTP), pituitary responsiveness to LH-RH in androgen-sterilized rats was lower than in control rats, which suggests that the subnormal response in the estrogen-treated rats was not due to a relative insensitivity to estrogen in the androgen-sterilized rats. The relatively high pituitary responsiveness to LH-RH in intact androgen-sterilized rats is probably due to the high circulating estrogen levels. The subnormal pituitary responsiveness to LH-RH after ovariectomy and estradiol treatment suggests, in addition to an effect on the hypothalamus, also a direct effect of neonatal androgen administration on the pituitary.", "contents": "Pituitary responsiveness to LH-RH in intact and ovariectomized androgen-sterilized rats. Serum LH changes in response to LH-RH injection were measured in intact and ovariectomized, steroid-treated female rats which were androgenized neonatally with 1,250 microgram testosterone propionate (TP) on day 5. At a dose of 20 ng LH-RH/100 g b.w., serum LH levels in intact rats increased over pre-injection levels, and at a dose of 100 ng LH-RH/100 g b.w., LH concentrations 15 min after injection were higher in nembutal-blocked proestrous rats than in androgen-sterilized rats. However, the ovulation response was not different between the groups. In ovariectomized estradiol benzoate (EB)-treated, androgen-sterilized rats, serum LH concentrations 15 and 60 min after LH-RH injection were lower than in similarly treated control rats. This effect was not secondary to the anovulatory state of the animal, since it also occurred in ovariectomized EB-treated prepuberal rats and in rats ovariectomized prepuberally and treated with EB in adulthood. Also, after treatment with 5alpha-dihydrotestosterone propionate (5alpha-DHTP), pituitary responsiveness to LH-RH in androgen-sterilized rats was lower than in control rats, which suggests that the subnormal response in the estrogen-treated rats was not due to a relative insensitivity to estrogen in the androgen-sterilized rats. The relatively high pituitary responsiveness to LH-RH in intact androgen-sterilized rats is probably due to the high circulating estrogen levels. The subnormal pituitary responsiveness to LH-RH after ovariectomy and estradiol treatment suggests, in addition to an effect on the hypothalamus, also a direct effect of neonatal androgen administration on the pituitary."}
{"id": "PMID:19714", "title": "Melanocyte-stimulating hormone release-inhibiting factor (MIF): lack of dopaminergic and anticholinergic activity.", "content": "In a sensitive animal model under the control of a dopaminergic-cholinergic balance, showing striking similarity to the extrapyramidal system, MIF did not possess dopaminergic or anticholinergic properties either with acute or chronic administration of the drug.", "contents": "Melanocyte-stimulating hormone release-inhibiting factor (MIF): lack of dopaminergic and anticholinergic activity. In a sensitive animal model under the control of a dopaminergic-cholinergic balance, showing striking similarity to the extrapyramidal system, MIF did not possess dopaminergic or anticholinergic properties either with acute or chronic administration of the drug."}
{"id": "PMID:19716", "title": "Adenylate cyclase and guanylate cyclase of normal and denervated skeletal muscle.", "content": "Cyclic nucleotides mediate the intracellular effects of various extracellular influences. To explore the possibility that nerve-muscle influences are mediated by cyclic nucleotides, we studied the effect of denervation on the cyclase enzymes of rabbit gastrocnemius using the contralateral, unoperated limb as the control. Adenylate cyclase activity decreased dramatically after denervation, while guanylate cyclase activity increased several times in all tissue fractions studied. Neither enzyme demonstrated cholinergic responsiveness. The dramatic changes in cyclase activities following denervation could result from a role of these enzymes in the mediation of nerve-muscle influences.", "contents": "Adenylate cyclase and guanylate cyclase of normal and denervated skeletal muscle. Cyclic nucleotides mediate the intracellular effects of various extracellular influences. To explore the possibility that nerve-muscle influences are mediated by cyclic nucleotides, we studied the effect of denervation on the cyclase enzymes of rabbit gastrocnemius using the contralateral, unoperated limb as the control. Adenylate cyclase activity decreased dramatically after denervation, while guanylate cyclase activity increased several times in all tissue fractions studied. Neither enzyme demonstrated cholinergic responsiveness. The dramatic changes in cyclase activities following denervation could result from a role of these enzymes in the mediation of nerve-muscle influences."}
{"id": "PMID:19719", "title": "Takayasu's syndrome in pregnancy.", "content": "Two cases of Takayasu's syndrome in pregnancy are presented. The obstetric courses of these women are compared with those of 7 others described in the literature. Symptoms of this rare condition may respond variably during pregnancy. Of the 9 women, 5 had worsening of their symptoms during gestation while 4 had milder symptoms than they had had prior to pregnancy. The best therapy is rest. Vaginal delivery is recommended and cesarean section should be reserved for obstetric indications.", "contents": "Takayasu's syndrome in pregnancy. Two cases of Takayasu's syndrome in pregnancy are presented. The obstetric courses of these women are compared with those of 7 others described in the literature. Symptoms of this rare condition may respond variably during pregnancy. Of the 9 women, 5 had worsening of their symptoms during gestation while 4 had milder symptoms than they had had prior to pregnancy. The best therapy is rest. Vaginal delivery is recommended and cesarean section should be reserved for obstetric indications."}
{"id": "PMID:19721", "title": "The role of mineral surfaces in the origin of life.", "content": "Adsorption of nucleoside phosphates on the surfaces of volcanic rocks has been studied. Differences in the absorption of some nucleoside phosphates on the surface of basalt cinder have been found. Differences in the adsorption of similar molecules on different mineral surfaces have also been shown. Different adsorptive capacities may have served as a mechanism for the selection of organic molecules during prebiotic evolution.", "contents": "The role of mineral surfaces in the origin of life. Adsorption of nucleoside phosphates on the surfaces of volcanic rocks has been studied. Differences in the absorption of some nucleoside phosphates on the surface of basalt cinder have been found. Differences in the adsorption of similar molecules on different mineral surfaces have also been shown. Different adsorptive capacities may have served as a mechanism for the selection of organic molecules during prebiotic evolution."}
{"id": "PMID:19724", "title": "Management of the child with recurrent asthma.", "content": "A rational approach to the evaluation of the child with chronic asthma has been presented. The importance of careful historical, physical, and pulmonary assessment is stressed, especially since asthma may exist without overt wheezing. General allergic as well as sequential pharmacologic management of this disease is also discussed. A knowledge of the biochemical and pathophysiologic alterations in asthma should lead to rational and specific therapy that preserves normal function and decreases the long-term morbidity and mortality of the disease.", "contents": "Management of the child with recurrent asthma. A rational approach to the evaluation of the child with chronic asthma has been presented. The importance of careful historical, physical, and pulmonary assessment is stressed, especially since asthma may exist without overt wheezing. General allergic as well as sequential pharmacologic management of this disease is also discussed. A knowledge of the biochemical and pathophysiologic alterations in asthma should lead to rational and specific therapy that preserves normal function and decreases the long-term morbidity and mortality of the disease."}
{"id": "PMID:19725", "title": "Early-onset pneumococcal sepsis in newborn infants.", "content": "Five infants with pneumococcal sepsis presented with respiratory distress and clinical signs of infection in the first day of life. Although there was no apparent epidemiological relationship among the patients, four of the five were seen within a 12-month period. Pneumonia, prolonged rupture of fetal membranes, and prematurity were features in these patients. Three infants died, two within 12 hours of diagnosis. Streptococcus pneumoniae was isolated from the vagina of three of the mothers; in two, the serotype was identical to that recovered from their infants. Clinical features of neonatal pneumococcal sepsis are similar to those of early-onset group B streptococcal infection. Like the group B Streptococcus, S. pneumoniae acquired from the maternal vagina is a potential life-threatening pathogen in the newborn period.", "contents": "Early-onset pneumococcal sepsis in newborn infants. Five infants with pneumococcal sepsis presented with respiratory distress and clinical signs of infection in the first day of life. Although there was no apparent epidemiological relationship among the patients, four of the five were seen within a 12-month period. Pneumonia, prolonged rupture of fetal membranes, and prematurity were features in these patients. Three infants died, two within 12 hours of diagnosis. Streptococcus pneumoniae was isolated from the vagina of three of the mothers; in two, the serotype was identical to that recovered from their infants. Clinical features of neonatal pneumococcal sepsis are similar to those of early-onset group B streptococcal infection. Like the group B Streptococcus, S. pneumoniae acquired from the maternal vagina is a potential life-threatening pathogen in the newborn period."}
{"id": "PMID:19722", "title": "[Effect of the landscape and climate on the distribution of blood-sucking mosquitoes in Murmansk Province].", "content": "According to its orographic characteristics and climate the Murmansk region represents a special landscape area of the Atlantic-Arctic zone with its peculiar zoogeographic characters. This specificity is clearly seen in the distribution of 19 species of bloodsucking mosquitoes over the above territory. Abundant and widely encountered are only two species, Aedes punctor and Ae. communis. 9 species, Culiseta alaskaensis, C. bergrothi, Aedes pullatus, Ae. excrucians, Ae. pionips, Ae. hexodontus, Ae. impiger, Ae. nigripes, Ae. diantaeus, are small in number and widely distributed. 8 species, Anopheles maculipennis, Aedes intrudens, Ae. cantans, Ae. cinereus, Ae. cataphylla, Ae. riparins, Ae. lencomelas, Culex pipiens pipiens, are rare and have a restricted distribution.", "contents": "[Effect of the landscape and climate on the distribution of blood-sucking mosquitoes in Murmansk Province]. According to its orographic characteristics and climate the Murmansk region represents a special landscape area of the Atlantic-Arctic zone with its peculiar zoogeographic characters. This specificity is clearly seen in the distribution of 19 species of bloodsucking mosquitoes over the above territory. Abundant and widely encountered are only two species, Aedes punctor and Ae. communis. 9 species, Culiseta alaskaensis, C. bergrothi, Aedes pullatus, Ae. excrucians, Ae. pionips, Ae. hexodontus, Ae. impiger, Ae. nigripes, Ae. diantaeus, are small in number and widely distributed. 8 species, Anopheles maculipennis, Aedes intrudens, Ae. cantans, Ae. cinereus, Ae. cataphylla, Ae. riparins, Ae. lencomelas, Culex pipiens pipiens, are rare and have a restricted distribution."}
{"id": "PMID:19726", "title": "The effects of pH on the conductance change evoked by iontophoresis in the frog neuromuscular junction.", "content": "The amplitude of the electrophoretically evoked end-plate potential increases with changing the pH of the bathing solution from 9.4 to 5.4 at room temperature. This change is not observed at lower temperature. The underlying current (e.p.c.I) is slightly decreasing at room temperature by lowering the pH. The relationship between the amplitude of the e.p.c.I and membrane potential is highly non-linear at pH 9.4, while it is quite linear at pH 5.4. The time course of the e.p.c.I is changed neither by different pH, nor by different membrane potential. The data suggest that during the e.p.c.I, the mediator (ACh), the receptor (R) and the mediator-receptor complex are in equilibrium: the amplitude of the e.p.c.I will thus depend on the affinity constant of the reversible reaction between ACh and R. It is concluded that by decreasing the pH, the affinity constant is decreased.", "contents": "The effects of pH on the conductance change evoked by iontophoresis in the frog neuromuscular junction. The amplitude of the electrophoretically evoked end-plate potential increases with changing the pH of the bathing solution from 9.4 to 5.4 at room temperature. This change is not observed at lower temperature. The underlying current (e.p.c.I) is slightly decreasing at room temperature by lowering the pH. The relationship between the amplitude of the e.p.c.I and membrane potential is highly non-linear at pH 9.4, while it is quite linear at pH 5.4. The time course of the e.p.c.I is changed neither by different pH, nor by different membrane potential. The data suggest that during the e.p.c.I, the mediator (ACh), the receptor (R) and the mediator-receptor complex are in equilibrium: the amplitude of the e.p.c.I will thus depend on the affinity constant of the reversible reaction between ACh and R. It is concluded that by decreasing the pH, the affinity constant is decreased."}
{"id": "PMID:19727", "title": "An automatically balancing isolation amplifier for the decoupling of measuring systems with high impedances.", "content": "It is theoretically shown that different conditions of coupling and grounding cause error voltages with the simultaneous use of two high-impedance measuring systems (e.g. pH electrodes). By the use of special amplifiers using optical transmission systems these error voltages are prevented. The transmission characteristics of the couplers are sensitive to changes in temperature due to the incorporation of infrared emitters in the system. An amplifying equipment with high d. c. stability was developed. The temperature drift was suppressed by the use of a special chopper stabilisation.", "contents": "An automatically balancing isolation amplifier for the decoupling of measuring systems with high impedances. It is theoretically shown that different conditions of coupling and grounding cause error voltages with the simultaneous use of two high-impedance measuring systems (e.g. pH electrodes). By the use of special amplifiers using optical transmission systems these error voltages are prevented. The transmission characteristics of the couplers are sensitive to changes in temperature due to the incorporation of infrared emitters in the system. An amplifying equipment with high d. c. stability was developed. The temperature drift was suppressed by the use of a special chopper stabilisation."}
{"id": "PMID:19729", "title": "Shear degradation of DNA.", "content": "A concentric-cylinder flow-birefringence instrument is used to generate sufficient shear fields to break T2 DNA (M = 1.2 X 10(8)) and E. coli DNA (M = 2.5 X 10(9)) in dilute solution. Breakage is monitored in situ by measuring the change in birefringence relaxation after the flow has been stopped. The breakage of T2 DNA follows first-order kinetics. Rate constants are obtained as functions of shear rate and viscosity (varied by adding glycerol). The data are fitted by a modified Arrhenius equation, assuming that stess increases the rate by lowering the activation energy. The rate increases with temperature, pH, and water concentration, and appears to be a base-catalyzed hydrolysis of the phosphate-ester linkage. La3+ ions catalyze the reaction. E. coli DNA was reduced to half molecules at a shear stress of 0.4 dynes/cm2, which is about 2500 times less than that required for T2. The difference in rates is accounted for in part by the difference in size of the two, but may also reflect the presence of many single-strand nicks in the coli DNA.", "contents": "Shear degradation of DNA. A concentric-cylinder flow-birefringence instrument is used to generate sufficient shear fields to break T2 DNA (M = 1.2 X 10(8)) and E. coli DNA (M = 2.5 X 10(9)) in dilute solution. Breakage is monitored in situ by measuring the change in birefringence relaxation after the flow has been stopped. The breakage of T2 DNA follows first-order kinetics. Rate constants are obtained as functions of shear rate and viscosity (varied by adding glycerol). The data are fitted by a modified Arrhenius equation, assuming that stess increases the rate by lowering the activation energy. The rate increases with temperature, pH, and water concentration, and appears to be a base-catalyzed hydrolysis of the phosphate-ester linkage. La3+ ions catalyze the reaction. E. coli DNA was reduced to half molecules at a shear stress of 0.4 dynes/cm2, which is about 2500 times less than that required for T2. The difference in rates is accounted for in part by the difference in size of the two, but may also reflect the presence of many single-strand nicks in the coli DNA."}
{"id": "PMID:19730", "title": "Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide.", "content": "The thermal stabilities of RNA:DNA hybrids are substantially greater than those of DNA:DNA duplexes in aqueous electrolyte solutions containing high concentrations of formamide. Association rates to form DNA:DNA duplexes and DNA:RNA hybrids have been measured in these solvents. There is a temperature range in which DNA:DNA rates are negligible and RNA:DNA rates close to optimal.", "contents": "Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide. The thermal stabilities of RNA:DNA hybrids are substantially greater than those of DNA:DNA duplexes in aqueous electrolyte solutions containing high concentrations of formamide. Association rates to form DNA:DNA duplexes and DNA:RNA hybrids have been measured in these solvents. There is a temperature range in which DNA:DNA rates are negligible and RNA:DNA rates close to optimal."}
{"id": "PMID:19731", "title": "The properties of native and denatured DNA in buoyant rubidium trichloroacetate at neutral pH.", "content": "Aqueous RbTCA is generally suitable as a buoyant solvent for both native and denatured DNA at neutral pH and room temperature. Native PM-2 DNA II, for example, is buoyant at 3.29 M salt, 25 degrees C; whereas the denatured strands band together at 4.52 M. Two properties of the solvent make this system uniquely useful for separations based upon the extent of secondary structure. First, the melting transition temperature for chemically unaltered DNA is depressed to room temperature or below. Second, the buoyant density increase accompanying denaturation is extraordinarily large, 174 mg/ml for PM-2 DNA II. This value is three times that found in aqueous NaI and ten times that for CsCl. The properties of the RbTCA buoyant solvent presented here include the compositional and buoyant density gradients and the buoyant density dependence upon base composition. The DNA remains chemically unaltered after exposure to RbTCA as shown by the absence of strand scissions for closed circular DNA and by the unimpaired biological activity in transformation assays. Intact virion DNA may be isolated by direct banding of whole virions in RbTCA gradients without prior phenol extraction. Strongly complexed or covalently bound proteins may be detected by their association with the buoyant polymer in the denaturing density gradient.", "contents": "The properties of native and denatured DNA in buoyant rubidium trichloroacetate at neutral pH. Aqueous RbTCA is generally suitable as a buoyant solvent for both native and denatured DNA at neutral pH and room temperature. Native PM-2 DNA II, for example, is buoyant at 3.29 M salt, 25 degrees C; whereas the denatured strands band together at 4.52 M. Two properties of the solvent make this system uniquely useful for separations based upon the extent of secondary structure. First, the melting transition temperature for chemically unaltered DNA is depressed to room temperature or below. Second, the buoyant density increase accompanying denaturation is extraordinarily large, 174 mg/ml for PM-2 DNA II. This value is three times that found in aqueous NaI and ten times that for CsCl. The properties of the RbTCA buoyant solvent presented here include the compositional and buoyant density gradients and the buoyant density dependence upon base composition. The DNA remains chemically unaltered after exposure to RbTCA as shown by the absence of strand scissions for closed circular DNA and by the unimpaired biological activity in transformation assays. Intact virion DNA may be isolated by direct banding of whole virions in RbTCA gradients without prior phenol extraction. Strongly complexed or covalently bound proteins may be detected by their association with the buoyant polymer in the denaturing density gradient."}
{"id": "PMID:19738", "title": "Model for \"charge-relay\": acceleration by carboxylate anion in intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group.", "content": "The effect of benzoate anion on intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group in endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate was examined in dioxane/H(2)O solutions. Benzoate anion exhibited a remarkable acceleration of the intramolecular general base-catalyzed hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate by the imidazolyl group. The rate of hydrolysis in the presence of the benzoate anion increased with the dioxane mole fraction and was proportional to the concentration of benzoate anion. On the other hand, the rate of hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate in the absence of benzoate anion decreased with the dioxane mole fraction. Thus, the ratio of the rate in the presence of benzoate anion to that in the absence of benzoate anion drastically increased with the dioxane mole fraction and attained a 2500-fold rate acceleration at a dioxane mole fraction of 0.42 (the highest experimentally attainable) when the concentration of benzoate anion was 0.5 M. The proposed mechanism involves proton abstraction by the benzoate anion from the imidazolyl group, followed by proton abstraction by the imidazolyl group from H(2)O, resulting in effective general base-catalysis of hydrolysis. The results of the present paper provide support for the \"charge-relay\" system in serine proteases.", "contents": "Model for \"charge-relay\": acceleration by carboxylate anion in intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group. The effect of benzoate anion on intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group in endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate was examined in dioxane/H(2)O solutions. Benzoate anion exhibited a remarkable acceleration of the intramolecular general base-catalyzed hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate by the imidazolyl group. The rate of hydrolysis in the presence of the benzoate anion increased with the dioxane mole fraction and was proportional to the concentration of benzoate anion. On the other hand, the rate of hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate in the absence of benzoate anion decreased with the dioxane mole fraction. Thus, the ratio of the rate in the presence of benzoate anion to that in the absence of benzoate anion drastically increased with the dioxane mole fraction and attained a 2500-fold rate acceleration at a dioxane mole fraction of 0.42 (the highest experimentally attainable) when the concentration of benzoate anion was 0.5 M. The proposed mechanism involves proton abstraction by the benzoate anion from the imidazolyl group, followed by proton abstraction by the imidazolyl group from H(2)O, resulting in effective general base-catalysis of hydrolysis. The results of the present paper provide support for the \"charge-relay\" system in serine proteases."}
{"id": "PMID:19739", "title": "Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems.", "content": "Escherichia coli glutamine synthetase and glycogen phosphorylase are prototypes for models of \"closed\" and \"opened\" bicyclic cascade systems. Steady-state functions relating the fractional activation of interconvertible enzymes to the concentrations of allosteric effectors and to the catalytic constants of the several converter enzymes in such cascades were determined. The study shows that when the active form of an interconvertible enzyme in one cycle catalyzes the covalent modification of the interconvertible enzyme in a second cycle, the two cycles become coupled, such that the fractional activity of the second interconvertible enzyme is a multiplicative function of all parameters in both cycles, i.e., of 14 and 18 parameters for the closed and the opened bicyclic cascade, respectively. Therefore, from the standpoint of cellular regulation, bicyclic cascades are superior to the monocyclic cascades analyzed previously [E. R. Stadtman & P. B. Chock (1977) Proc. Natl. Acad. Sci. USA 74, 2761-2765], because: (i) they can respond to a greater number of allosteric effectors; (ii) they can achieve much greater amplification of responses to primary stimuli (e.g., with only 2-fold changes in each parameter the amplification factors of one-cycle and two-cycle cascades are 320 and 102,400, respectively); (iii) they can generate a sigmoidal response (Hill numbers of >2) of interconvertible enzyme activity to increasing concentrations of an allosteric effector. This is because there are more steps in a bicyclic cascade at which a given effector can interact. A similar analysis of multicyclic cascade systems shows that the capacity for amplification increases exponentially as the number of cycles in the cascade increases. In addition, regulation by cyclic cascades can achieve enormous variability of the fractional activity of the interconvertible enzyme by shifting the steady-state distribution between active and inactive forms. One equivalent of ATP is consumed in each interconversion cycle to provide the energy needed to maintain the steady-state activity of the modified enzyme at a metabolically required level. Therefore, the decomposition of ATP associated with the cyclic cascade is not a wasteful process.", "contents": "Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems. Escherichia coli glutamine synthetase and glycogen phosphorylase are prototypes for models of \"closed\" and \"opened\" bicyclic cascade systems. Steady-state functions relating the fractional activation of interconvertible enzymes to the concentrations of allosteric effectors and to the catalytic constants of the several converter enzymes in such cascades were determined. The study shows that when the active form of an interconvertible enzyme in one cycle catalyzes the covalent modification of the interconvertible enzyme in a second cycle, the two cycles become coupled, such that the fractional activity of the second interconvertible enzyme is a multiplicative function of all parameters in both cycles, i.e., of 14 and 18 parameters for the closed and the opened bicyclic cascade, respectively. Therefore, from the standpoint of cellular regulation, bicyclic cascades are superior to the monocyclic cascades analyzed previously [E. R. Stadtman & P. B. Chock (1977) Proc. Natl. Acad. Sci. USA 74, 2761-2765], because: (i) they can respond to a greater number of allosteric effectors; (ii) they can achieve much greater amplification of responses to primary stimuli (e.g., with only 2-fold changes in each parameter the amplification factors of one-cycle and two-cycle cascades are 320 and 102,400, respectively); (iii) they can generate a sigmoidal response (Hill numbers of >2) of interconvertible enzyme activity to increasing concentrations of an allosteric effector. This is because there are more steps in a bicyclic cascade at which a given effector can interact. A similar analysis of multicyclic cascade systems shows that the capacity for amplification increases exponentially as the number of cycles in the cascade increases. In addition, regulation by cyclic cascades can achieve enormous variability of the fractional activity of the interconvertible enzyme by shifting the steady-state distribution between active and inactive forms. One equivalent of ATP is consumed in each interconversion cycle to provide the energy needed to maintain the steady-state activity of the modified enzyme at a metabolically required level. Therefore, the decomposition of ATP associated with the cyclic cascade is not a wasteful process."}
{"id": "PMID:19737", "title": "[Enzyme immobilization on hydrated oxides of transition metals and aluminum].", "content": "The immobilization of alpha-chymotrypsin, trypsin and invertase on hydrated oxides of tin, titanium and aluminium was investigated. The degree at which the enzymes were bound upon immobilization was 83.2-2.6%. The amount of bound proteins was 64.2 mg/g carrier. The specific activity of enzymes reached the highest level in the case of hydrated tin oxide and amounted to 76.8%, 49.9% and 99.6%, of activity of native alpha-chymotrypsin, trypsin and invertase, respectively. The thermal stability of immobilized proteases was considerably higher and that of immobilized invertase was significantly lower than that of native enzymes. The pH optimum of immobilized enzymes shifted by 0.6-2.6 units towards the alkaline region.", "contents": "[Enzyme immobilization on hydrated oxides of transition metals and aluminum]. The immobilization of alpha-chymotrypsin, trypsin and invertase on hydrated oxides of tin, titanium and aluminium was investigated. The degree at which the enzymes were bound upon immobilization was 83.2-2.6%. The amount of bound proteins was 64.2 mg/g carrier. The specific activity of enzymes reached the highest level in the case of hydrated tin oxide and amounted to 76.8%, 49.9% and 99.6%, of activity of native alpha-chymotrypsin, trypsin and invertase, respectively. The thermal stability of immobilized proteases was considerably higher and that of immobilized invertase was significantly lower than that of native enzymes. The pH optimum of immobilized enzymes shifted by 0.6-2.6 units towards the alkaline region."}
{"id": "PMID:19740", "title": "Defective organization of actin in cultured skin fibroblasts from patients with inherited adenocarcinoma.", "content": "In the cytoplasm of well-spread cultured normal fibroblasts, actin is organized into a network of cables that run the length of the cell just inside the adherent cell membrane. A diffuse matrix replaces the cables in fibroblasts that have become tumorigenic as a result of oncogenic transformation. We have found a similar disruption in actin organization in cultured skin fibroblasts (passage 6-10) obtained by biopsy from patients with the inherited colonic cancer, adenomatosis of the colon and rectum (ACR). Because ACR is inherited as an autosomal dominant trait, about half the children of ACR patients will develop colon cancer, but they typically remain asymptomatic until at least the second decade of life. Actin distribution within cultured cells from children of ACR patients was identical either to that seen in cultured cells from normal persons or to that seen in cultured cells from ACR patients. The two different patterns were independent of age, sex, drug treatment, or infections of the donors. Apparently, this class of colonic carcinoma is accompanied by a systemic aberration in the organization of fibroblast cytoplasm, and this aberration can be detected by immunofluorescent localization of actin within cultured skin fibroblasts, prior to manifestation of any colonic symptoms.", "contents": "Defective organization of actin in cultured skin fibroblasts from patients with inherited adenocarcinoma. In the cytoplasm of well-spread cultured normal fibroblasts, actin is organized into a network of cables that run the length of the cell just inside the adherent cell membrane. A diffuse matrix replaces the cables in fibroblasts that have become tumorigenic as a result of oncogenic transformation. We have found a similar disruption in actin organization in cultured skin fibroblasts (passage 6-10) obtained by biopsy from patients with the inherited colonic cancer, adenomatosis of the colon and rectum (ACR). Because ACR is inherited as an autosomal dominant trait, about half the children of ACR patients will develop colon cancer, but they typically remain asymptomatic until at least the second decade of life. Actin distribution within cultured cells from children of ACR patients was identical either to that seen in cultured cells from normal persons or to that seen in cultured cells from ACR patients. The two different patterns were independent of age, sex, drug treatment, or infections of the donors. Apparently, this class of colonic carcinoma is accompanied by a systemic aberration in the organization of fibroblast cytoplasm, and this aberration can be detected by immunofluorescent localization of actin within cultured skin fibroblasts, prior to manifestation of any colonic symptoms."}
{"id": "PMID:19741", "title": "A protonmotive force drives bacterial flagella.", "content": "Streptococcus strain V4051 is motile in the presence of glucose. The cells move steadily along smooth paths (run), jump about briefly with little net displacement (twiddle), and then run in new directions. They stop swimming when deprived of glucose. These cells become motile when an electrical potential or a pH gradient is imposed across the membrane. Starved cells suspended in a potassium-free medium respond to the addition of valinomycin by a brief period of vigorous twiddling. They also twiddle, although less vigorously, when the external pH is lowered. Valinomycin-induced twiddling occurs in the absence of external alkali or alkaline earth cations and without significant net synthesis of ATP. When a chemoattractant is added to cells swimming in the presence of glucose, twiddles are transiently suppressed, and the cells run for a time. Similarly, when starved cells are suspended in a potassium-free medium containing both valinomycin and an attractant, many cells initially run rather than twiddle. We conclude that the flagella are driven by a protonmotive force.", "contents": "A protonmotive force drives bacterial flagella. Streptococcus strain V4051 is motile in the presence of glucose. The cells move steadily along smooth paths (run), jump about briefly with little net displacement (twiddle), and then run in new directions. They stop swimming when deprived of glucose. These cells become motile when an electrical potential or a pH gradient is imposed across the membrane. Starved cells suspended in a potassium-free medium respond to the addition of valinomycin by a brief period of vigorous twiddling. They also twiddle, although less vigorously, when the external pH is lowered. Valinomycin-induced twiddling occurs in the absence of external alkali or alkaline earth cations and without significant net synthesis of ATP. When a chemoattractant is added to cells swimming in the presence of glucose, twiddles are transiently suppressed, and the cells run for a time. Similarly, when starved cells are suspended in a potassium-free medium containing both valinomycin and an attractant, many cells initially run rather than twiddle. We conclude that the flagella are driven by a protonmotive force."}
{"id": "PMID:19742", "title": "Electrical stimulation of preganglionic nerve increases tyrosine hydroxylase activity in sympathetic ganglia.", "content": "The effect of synaptic stimulation on tyrosine hydroxylase [tyrosine 3-monooxygenase: L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity in the rat superior cervical ganglion was studied. The preganglionic cervical sympathetic trunk was stimulated unilaterally at 10 Hz for 30 min. Forty-eight hours later tyrosine hydroxylase activity was 33% higher on the stimulated than on the control side. The enzyme activity restimulated than on the control side. The enzyme activity remained elevated in the stimulated ganglia for 2 days. No change was observed in total ganglion protein. Comparable increases in tyrosine hydroxylase activity were observed in anesthetized and conscious animals.", "contents": "Electrical stimulation of preganglionic nerve increases tyrosine hydroxylase activity in sympathetic ganglia. The effect of synaptic stimulation on tyrosine hydroxylase [tyrosine 3-monooxygenase: L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity in the rat superior cervical ganglion was studied. The preganglionic cervical sympathetic trunk was stimulated unilaterally at 10 Hz for 30 min. Forty-eight hours later tyrosine hydroxylase activity was 33% higher on the stimulated than on the control side. The enzyme activity restimulated than on the control side. The enzyme activity remained elevated in the stimulated ganglia for 2 days. No change was observed in total ganglion protein. Comparable increases in tyrosine hydroxylase activity were observed in anesthetized and conscious animals."}
{"id": "PMID:19771", "title": "Some characteristics of amnesia induced by FLA-63 an inhibitor of dopamine beta hydroxylase.", "content": "The amnesic effects of FLA-63, a potent dopamine-beta-hydroxylase (DBH) inhibitor, were investigated in a food motivated spatial discrimination task. Groups of C57BL/6J mice were injected with either 5 mg/kg, 15 mg/kg, 25 mg/kg, 35 mg/kg or physiological saline 4 hr prior to training. Amnesia was observed 24 hr following training at all dose levels except 5 mg/kh. The performance deficit was specific to memory of the discrimination and not the result of state-dependency. Training conditions which produce an increase in habit strength prevented the amnestic effects of FLS-63. Spontaneous recovery of memory occurred 48 hr following drug administration. Recovery from amnesia was also induced by injections of a monoamine oxidase inhibitor, pargyline, administered 2 hr prior to the retention test. These data suggest that amnesia induced by norpinephrine (NE) depletion is the result of impairment of mechanisms necessary for memory retrieval.", "contents": "Some characteristics of amnesia induced by FLA-63 an inhibitor of dopamine beta hydroxylase. The amnesic effects of FLA-63, a potent dopamine-beta-hydroxylase (DBH) inhibitor, were investigated in a food motivated spatial discrimination task. Groups of C57BL/6J mice were injected with either 5 mg/kg, 15 mg/kg, 25 mg/kg, 35 mg/kg or physiological saline 4 hr prior to training. Amnesia was observed 24 hr following training at all dose levels except 5 mg/kh. The performance deficit was specific to memory of the discrimination and not the result of state-dependency. Training conditions which produce an increase in habit strength prevented the amnestic effects of FLS-63. Spontaneous recovery of memory occurred 48 hr following drug administration. Recovery from amnesia was also induced by injections of a monoamine oxidase inhibitor, pargyline, administered 2 hr prior to the retention test. These data suggest that amnesia induced by norpinephrine (NE) depletion is the result of impairment of mechanisms necessary for memory retrieval."}
{"id": "PMID:19772", "title": "Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs.", "content": "Presented in this paper are the effects of chlorpromazine, clozapine, d-amphetamine and diazepam on DRL behavior in rats. D-Amphetamine and diazepam, which showed similar effects on response errors, could be identified on the basis of burst responding and drug interaction. Clozapine, a new antipsychotic agent which does not cause extrapyramidal side effect in man affected DRL behavior in the same way as did chlorpromazine. Thus, DRL schedules are probably not useful in differentiating various neuroleptic agents.", "contents": "Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs. Presented in this paper are the effects of chlorpromazine, clozapine, d-amphetamine and diazepam on DRL behavior in rats. D-Amphetamine and diazepam, which showed similar effects on response errors, could be identified on the basis of burst responding and drug interaction. Clozapine, a new antipsychotic agent which does not cause extrapyramidal side effect in man affected DRL behavior in the same way as did chlorpromazine. Thus, DRL schedules are probably not useful in differentiating various neuroleptic agents."}
{"id": "PMID:19784", "title": "Plasticity in mammalian skeletal muscle.", "content": "While it has been recognized for many years that different limb muscles belonging to the same mammal may have markedly differing contractile characteristics, it is only comparatively recently that it has been demonstrated that these differences depend upon the motor innervation. By appropriately changing the peripheral nerve innervating a mammalian skeletal muscle, it is possible to change dramatically the contractile behaviour of the reinnervated muscle. The manner by which the motor innervation determines the nature of a muscle fibre's contractile machinery is not completely understood, but it appears that the number and pattern of motor nerve impulses reaching the muscle play an important role. The biochemical changes occurring within muscle fibres whose contractile properties have been modified by altered motor innervation include the synthesis of different contractile proteins.", "contents": "Plasticity in mammalian skeletal muscle. While it has been recognized for many years that different limb muscles belonging to the same mammal may have markedly differing contractile characteristics, it is only comparatively recently that it has been demonstrated that these differences depend upon the motor innervation. By appropriately changing the peripheral nerve innervating a mammalian skeletal muscle, it is possible to change dramatically the contractile behaviour of the reinnervated muscle. The manner by which the motor innervation determines the nature of a muscle fibre's contractile machinery is not completely understood, but it appears that the number and pattern of motor nerve impulses reaching the muscle play an important role. The biochemical changes occurring within muscle fibres whose contractile properties have been modified by altered motor innervation include the synthesis of different contractile proteins."}
{"id": "PMID:19785", "title": "Early visual experience, learning, and neurochemical plasticity in the rat and the chick.", "content": "Rats reared in the dark to 50 days show morphological and biochemical changes in the visual pathway. Light exposure results in elevated incorporation into protein in visual cortex, lateral geniculate and retina. Much of the visual cortex elevation is in a rapidly labelling, rapidly transported neuronal particulate protein. There are concomitant changes in lysosomal and transmitter enzyme activity. In chicks exposed to an imprinting stimulus (a flashing light) there are elevations in RNA polymerase and RNA and protein incorporation in the anterior forebrain roof (a.f.r.) compared with controls. There are changes in adenyl cyclase, cAMP and AChE. Behavioural controls show that although there are general biochemical sequelae of light exposure, the elevation in RNA synthesis in the a.f.r. is not a result of motor, stress or sensory activity, but is correlated with a measure of the learning of the stimulus characteristics. A model for neurochemical correlates of developmental plasticity, learning, and state-dependent transients is discussed.", "contents": "Early visual experience, learning, and neurochemical plasticity in the rat and the chick. Rats reared in the dark to 50 days show morphological and biochemical changes in the visual pathway. Light exposure results in elevated incorporation into protein in visual cortex, lateral geniculate and retina. Much of the visual cortex elevation is in a rapidly labelling, rapidly transported neuronal particulate protein. There are concomitant changes in lysosomal and transmitter enzyme activity. In chicks exposed to an imprinting stimulus (a flashing light) there are elevations in RNA polymerase and RNA and protein incorporation in the anterior forebrain roof (a.f.r.) compared with controls. There are changes in adenyl cyclase, cAMP and AChE. Behavioural controls show that although there are general biochemical sequelae of light exposure, the elevation in RNA synthesis in the a.f.r. is not a result of motor, stress or sensory activity, but is correlated with a measure of the learning of the stimulus characteristics. A model for neurochemical correlates of developmental plasticity, learning, and state-dependent transients is discussed."}
{"id": "PMID:19786", "title": "Plasticity in the adult vestibulo-ocular reflex arc.", "content": "Human subjects with maintained reversal of their horizontal field of vision exhibit very substantial adaptive changes in their 'horizontal' vestibulo-ocular reflex (v.o.r.). Short durations (8 min) of vision reversal during natural head movement led to 20% v.o.r. attenuation while long periods (4 weeks) eventually led to approximate reversal of the reflex. The reversed condition is approached by a complex, but highly systematic, series of changes in gain and phase of the reflex response relative to normal. Recovery after return to normal vision exhibits a similar duration, but different pattern, to that of the original adaptation. A chronic cat preparation with long-term optical reversal of vision has now been developed and shows similar adaptive and recovery changes at low test stimulus amplitudes, but different patterns of adaptive response at high amplitudes. An adaptive neural model employing known vestibulo-ocular pathways is proposed to account for these experimentally observed plastic changes. The model is used to predict the adapted response to patterns of stimulation extending beyond the range of experimental investigation.", "contents": "Plasticity in the adult vestibulo-ocular reflex arc. Human subjects with maintained reversal of their horizontal field of vision exhibit very substantial adaptive changes in their 'horizontal' vestibulo-ocular reflex (v.o.r.). Short durations (8 min) of vision reversal during natural head movement led to 20% v.o.r. attenuation while long periods (4 weeks) eventually led to approximate reversal of the reflex. The reversed condition is approached by a complex, but highly systematic, series of changes in gain and phase of the reflex response relative to normal. Recovery after return to normal vision exhibits a similar duration, but different pattern, to that of the original adaptation. A chronic cat preparation with long-term optical reversal of vision has now been developed and shows similar adaptive and recovery changes at low test stimulus amplitudes, but different patterns of adaptive response at high amplitudes. An adaptive neural model employing known vestibulo-ocular pathways is proposed to account for these experimentally observed plastic changes. The model is used to predict the adapted response to patterns of stimulation extending beyond the range of experimental investigation."}
{"id": "PMID:19787", "title": "Electrophysiological experiments on the mechanism and accuracy of neuromuscular specificity in the axolotl.", "content": "The supracoracoideus muscle of the axolotl shoulder girdle is innervated by two nerves, the supracoracoideus nerve (SC) supplying most of the muscle and the posterior supracoracoideus (PSC) supplying the posterior corner. All the muscle fibres are multiply innervated and at the border between the two innervations many muscle fibres, when penetrated by a microelectrode, show junction potentials from both nerves. In such cases one junction potential is often very small, below the threshold for exciting muscle contraction, the other large and effective at exciting the muscle. If the SC nerve is cut, the territory of the PSC nerve expands over several weeks. Upon regrowth of the cut nerve it reinnervates its old muscle fibres and removes the previous foreign innervation, the borderline between the two nerve territories being established exactly as before. This depends upon two processes, sprouting of nerves and a competitive repression of transmission from nerves ending on foreign muscle fibres.", "contents": "Electrophysiological experiments on the mechanism and accuracy of neuromuscular specificity in the axolotl. The supracoracoideus muscle of the axolotl shoulder girdle is innervated by two nerves, the supracoracoideus nerve (SC) supplying most of the muscle and the posterior supracoracoideus (PSC) supplying the posterior corner. All the muscle fibres are multiply innervated and at the border between the two innervations many muscle fibres, when penetrated by a microelectrode, show junction potentials from both nerves. In such cases one junction potential is often very small, below the threshold for exciting muscle contraction, the other large and effective at exciting the muscle. If the SC nerve is cut, the territory of the PSC nerve expands over several weeks. Upon regrowth of the cut nerve it reinnervates its old muscle fibres and removes the previous foreign innervation, the borderline between the two nerve territories being established exactly as before. This depends upon two processes, sprouting of nerves and a competitive repression of transmission from nerves ending on foreign muscle fibres."}
{"id": "PMID:19789", "title": "The presence of ineffective synapses and the circumstances which unmask them.", "content": "In this paper, we shall show that there are substantial numbers of nerve terminals which are normally ineffective. In the intact animal, occasional signs of the postsynaptic effectiveness of these fibres can be seen under conditions of optimal spatial summation or increased excitability or decreased inhibition. If the normally functioning afferent nerve fibres are blocked or cut, some of the previously ineffective fibres immediately establish an effective drive of cells. If the normal afferents are cut and allowed to degenerate, large numbers of cells begin to respond to new inputs. The presence of ineffective synapses in the adult offers an alternative to sprouting or the opening up of polysynaptic pathways as a possible mechanism to explain plasticity of connections in adult brains.", "contents": "The presence of ineffective synapses and the circumstances which unmask them. In this paper, we shall show that there are substantial numbers of nerve terminals which are normally ineffective. In the intact animal, occasional signs of the postsynaptic effectiveness of these fibres can be seen under conditions of optimal spatial summation or increased excitability or decreased inhibition. If the normally functioning afferent nerve fibres are blocked or cut, some of the previously ineffective fibres immediately establish an effective drive of cells. If the normal afferents are cut and allowed to degenerate, large numbers of cells begin to respond to new inputs. The presence of ineffective synapses in the adult offers an alternative to sprouting or the opening up of polysynaptic pathways as a possible mechanism to explain plasticity of connections in adult brains."}
{"id": "PMID:19801", "title": "Pharmacokinetics of N-desmethyldiazepam in healthy volunteers after single daily doses of dipotassium chlorazepate.", "content": "Dipotassium chlorazepate was administered to 12 healthy volunteers (8 males and 4 females), aged 22-38 years, as a single daily dose of 20 mg for 14 days. Plasma concentrations of N-desmethyldiazepam were monitored with a gas-chromatographic method during the medication period and for 5 days after withdrawal of the drug. The plasma half-life (t1/2), the elimination coefficient (Kbeta), the concentration (Css), and the apparent volume of distribution (Vbeta) were calculated at steady state, and the mean values +/- SEM were 53 +/- 6 h, 0.0147 +/- 0.0013 h-1, 884 +/- 73 ng/ml, and 1.13 +/- 0.08 1/kg, respectively. A moderate interindividual variability was observed regarding these parameters. There was no tendency toward a biexponential elimination. A significant difference in the apparent volume of distribution was found when males and females were compared.", "contents": "Pharmacokinetics of N-desmethyldiazepam in healthy volunteers after single daily doses of dipotassium chlorazepate. Dipotassium chlorazepate was administered to 12 healthy volunteers (8 males and 4 females), aged 22-38 years, as a single daily dose of 20 mg for 14 days. Plasma concentrations of N-desmethyldiazepam were monitored with a gas-chromatographic method during the medication period and for 5 days after withdrawal of the drug. The plasma half-life (t1/2), the elimination coefficient (Kbeta), the concentration (Css), and the apparent volume of distribution (Vbeta) were calculated at steady state, and the mean values +/- SEM were 53 +/- 6 h, 0.0147 +/- 0.0013 h-1, 884 +/- 73 ng/ml, and 1.13 +/- 0.08 1/kg, respectively. A moderate interindividual variability was observed regarding these parameters. There was no tendency toward a biexponential elimination. A significant difference in the apparent volume of distribution was found when males and females were compared."}
{"id": "PMID:19802", "title": "Morphine action in grouped and isolated rats and mice.", "content": "The present study determines the analgesic effects of morphine in grouped and isolated rats and mice. Isolated animals developed altered behavioral patterns, including mouse-killing in rats and mutual aggressiveness in mice. The analgesic effect of morphine was tested by tail compression in rats and by the hot plate for mice. Isolated rats developing mouse-killing behavior had a raised pain threshold, while indifferent animals (nonkillers) responded less to morphine. Isolated mice, particularly low aggressors, gave enhanced responses to morphine.", "contents": "Morphine action in grouped and isolated rats and mice. The present study determines the analgesic effects of morphine in grouped and isolated rats and mice. Isolated animals developed altered behavioral patterns, including mouse-killing in rats and mutual aggressiveness in mice. The analgesic effect of morphine was tested by tail compression in rats and by the hot plate for mice. Isolated rats developing mouse-killing behavior had a raised pain threshold, while indifferent animals (nonkillers) responded less to morphine. Isolated mice, particularly low aggressors, gave enhanced responses to morphine."}
{"id": "PMID:19803", "title": "Comparison of thyrotropin-releasing hormone with melanocyte-stimulating-hormone-release-inhibiting factor as pentobarbital antagonists in monkeys.", "content": "Thyrotropin-releasing hormone (TRH), 0.1 mg/kg, i.m., significantly counteracted pentobarbital narcosis in six monkeys, but melanocyte-stimulating-hormone-release-inhibiting factor (MIF), 0.1 mg/kg i.m., did not. Earlier dose-response studies in unanesthetized monkeys had shown that this dose of MIF stimulated motor activity; this dose of TRH had shown no stimulant effect, but a higher dose depressed activity. Thus, an MIF dose that stimulates unanesthetized monkeys does not reverse pentobarbital narcosis;  a TRH dose that by itself is neither stimulant nor depressant does partially reverse pentobarbital narcosis.", "contents": "Comparison of thyrotropin-releasing hormone with melanocyte-stimulating-hormone-release-inhibiting factor as pentobarbital antagonists in monkeys. Thyrotropin-releasing hormone (TRH), 0.1 mg/kg, i.m., significantly counteracted pentobarbital narcosis in six monkeys, but melanocyte-stimulating-hormone-release-inhibiting factor (MIF), 0.1 mg/kg i.m., did not. Earlier dose-response studies in unanesthetized monkeys had shown that this dose of MIF stimulated motor activity; this dose of TRH had shown no stimulant effect, but a higher dose depressed activity. Thus, an MIF dose that stimulates unanesthetized monkeys does not reverse pentobarbital narcosis;  a TRH dose that by itself is neither stimulant nor depressant does partially reverse pentobarbital narcosis."}
{"id": "PMID:19804", "title": "Dose- and time-dependent effects of narcotic analgesics on intracranial self-stimulation in the rat.", "content": "Rats were trained to bar-press in order to obtain electrical stimulation of the medial forebrain bundle through chronically implanted electrodes. Dose-response and time-effect curves were determined for morphine (1.0-30 mg/kg), levorphanol (0.1 to 3.0 mg/kg), methadone (0.1-3.0 mg/kg), meperidine (1.0-30 mg/kg), oxymorphone (0.03-1.0 mg/kg), and d-amphetamine (0.1-3.0 mg/kg). Dose-response and time-effect curves were also determined for morphine (1.0-30 mg/kg) in rats that had received multiple injections of morphine over a period of 3 days. All of the narcotic analgesics produced dose-related decreases in responding; the durations of these decreases were also dose-related. The relative potencies of the five narcotic analgesics with respect to the rate-decreasing effects for selt-stimulation responding were: oxymorphone greater than levorphanol greater than methadone greater than morphine greater than meperidine. In morphine-tolerant rats the rate-decreasing effects of morphine on responding for selt-stimulation were attenuated. These findings suggest that narcotic analgesics from diverse chemical families have a similar, predominantly depressant, effect on self-stimulation behavior and that the relative potencies of a series of narcotics for this effect are similar to those demonstrated for other properties of these drugs.", "contents": "Dose- and time-dependent effects of narcotic analgesics on intracranial self-stimulation in the rat. Rats were trained to bar-press in order to obtain electrical stimulation of the medial forebrain bundle through chronically implanted electrodes. Dose-response and time-effect curves were determined for morphine (1.0-30 mg/kg), levorphanol (0.1 to 3.0 mg/kg), methadone (0.1-3.0 mg/kg), meperidine (1.0-30 mg/kg), oxymorphone (0.03-1.0 mg/kg), and d-amphetamine (0.1-3.0 mg/kg). Dose-response and time-effect curves were also determined for morphine (1.0-30 mg/kg) in rats that had received multiple injections of morphine over a period of 3 days. All of the narcotic analgesics produced dose-related decreases in responding; the durations of these decreases were also dose-related. The relative potencies of the five narcotic analgesics with respect to the rate-decreasing effects for selt-stimulation responding were: oxymorphone greater than levorphanol greater than methadone greater than morphine greater than meperidine. In morphine-tolerant rats the rate-decreasing effects of morphine on responding for selt-stimulation were attenuated. These findings suggest that narcotic analgesics from diverse chemical families have a similar, predominantly depressant, effect on self-stimulation behavior and that the relative potencies of a series of narcotics for this effect are similar to those demonstrated for other properties of these drugs."}
{"id": "PMID:19805", "title": "Influence of the suspension of continued treatment with flurazepam and amobarbital on two discrimination learning schedules.", "content": "The authors have studied the effect of the suspension of chronic treatment with flurazepam and amobarbital on the operant behavior of rats that for the first time were in the presence of two fixed-interval discrimination schedules. With the sound discrimination schedule, the responses emitted by the treated animals had charactistics similar to those of control animals. With the temporal discrimination schedule, though it is not possible to distinguish between learning rates, modifications in the intensity of the effect (increases in lever pressing) indicate that, considering the doses, the action of flurazepam is slight and that of amobarbital clear and statistically significant.", "contents": "Influence of the suspension of continued treatment with flurazepam and amobarbital on two discrimination learning schedules. The authors have studied the effect of the suspension of chronic treatment with flurazepam and amobarbital on the operant behavior of rats that for the first time were in the presence of two fixed-interval discrimination schedules. With the sound discrimination schedule, the responses emitted by the treated animals had charactistics similar to those of control animals. With the temporal discrimination schedule, though it is not possible to distinguish between learning rates, modifications in the intensity of the effect (increases in lever pressing) indicate that, considering the doses, the action of flurazepam is slight and that of amobarbital clear and statistically significant."}
{"id": "PMID:19806", "title": "Blockade of intracranial self-stimulation by antipsychotic drugs: failure to correlate with central alpha-noradrenergic blockade.", "content": "The involvement of central alpha-noradrenergic receptors in intracranial self-stimulation (ICSS) was studied. Dose-response curves were established for the blockade of ICSS by the antipsychotic drugs chlorpromazine, thioridazine, clozapine, and pimozide and the alpha-antagonist phenoxybenzamine. Antagonism of the facilitation, produced by the central alpha-agonist clonidine, of flexor withdrawal reflexes in the reserpinized spinal rat was used to assess the central alpha-blocking potency of the same drugs, and dose-response curves were established. No correlation was found between central alpha-blockade, as reflected by the ED50 for blockade of clonidine-facilated spinal reflexes, and the ED50 for blockade of ICSS. Pimozide blocked ICSS at doses virtually devoid of central alpha-blocking activity, while phenoxybenzamine was a potent alpha-antagonist and a weak blocker of ICSS. The lack of correlation between central alpha-blockade and decreased ICSS suggests that alpha-receptors are not critically involved in self-stimulation behavior.", "contents": "Blockade of intracranial self-stimulation by antipsychotic drugs: failure to correlate with central alpha-noradrenergic blockade. The involvement of central alpha-noradrenergic receptors in intracranial self-stimulation (ICSS) was studied. Dose-response curves were established for the blockade of ICSS by the antipsychotic drugs chlorpromazine, thioridazine, clozapine, and pimozide and the alpha-antagonist phenoxybenzamine. Antagonism of the facilitation, produced by the central alpha-agonist clonidine, of flexor withdrawal reflexes in the reserpinized spinal rat was used to assess the central alpha-blocking potency of the same drugs, and dose-response curves were established. No correlation was found between central alpha-blockade, as reflected by the ED50 for blockade of clonidine-facilated spinal reflexes, and the ED50 for blockade of ICSS. Pimozide blocked ICSS at doses virtually devoid of central alpha-blocking activity, while phenoxybenzamine was a potent alpha-antagonist and a weak blocker of ICSS. The lack of correlation between central alpha-blockade and decreased ICSS suggests that alpha-receptors are not critically involved in self-stimulation behavior."}
{"id": "PMID:19807", "title": "Negative naloxone effects in schizophrenic patients.", "content": "On the basis of the hypothesis that the opiate-like neuropeptides, such as beta-endorphin, may be involved in the etiology of schizophrenic symptoms, naloxone 1,2 mg and placebo were administered intravenously to 8 schizophrenic patients, using a double-blind, crossover design. Naloxone was not found to be different from placebo in effecting schizophrenic symptoms, including hallucinations and delusions.", "contents": "Negative naloxone effects in schizophrenic patients. On the basis of the hypothesis that the opiate-like neuropeptides, such as beta-endorphin, may be involved in the etiology of schizophrenic symptoms, naloxone 1,2 mg and placebo were administered intravenously to 8 schizophrenic patients, using a double-blind, crossover design. Naloxone was not found to be different from placebo in effecting schizophrenic symptoms, including hallucinations and delusions."}
{"id": "PMID:19810", "title": "Effects of chronic hydrochloric and lactic acid administrations on food intake, blood acid-base balance and bone composition of the rat.", "content": "In experiment 1, weanling rats were given, for 7 weeks, a commercial rat diet supplemented with hydrochloric acid at levels up to 560 mmol.kg-1 dry matter. The supplement increased water intake but did not significantly affect food intake, live-weight gain, blood haemoglobin and haematocrit values or acid-base balance. In experiment 2, adult rats were given, for 9 weeks, a commercial rat diet supplemented with hydrochloric acid at levels up to 1250 mmol.kg-1 dry matter. Food intake and liveweight gain were not affected by hydrochloric acid concentration up to 625 mmole but at 938 mmol.kg-1 they were considerably reduced and there was 100% mortality of the rats. In experiment 3, weanling rats were given, for 12 weeks, a commercial rat diet supplemented with hydrochloric or lactic acid each at 300, 600 and 900 mmol.kg-1 dry matter. Lactic acid at the three levels and hydrochloric acid at the two lower levels did not affect food intake or live weight gain and had only a slight effect on blood acid-base balance. At a dietary concentration of 900 mmol.kg-1 dry matter, hydrochloric acid decreased food intake, induced a mild degree of metabolic acidosis and resulted in 30% mortality of the rats. In the three experiments, the acid treatments dnot directly affect the length or composition of the femur of the rats.", "contents": "Effects of chronic hydrochloric and lactic acid administrations on food intake, blood acid-base balance and bone composition of the rat. In experiment 1, weanling rats were given, for 7 weeks, a commercial rat diet supplemented with hydrochloric acid at levels up to 560 mmol.kg-1 dry matter. The supplement increased water intake but did not significantly affect food intake, live-weight gain, blood haemoglobin and haematocrit values or acid-base balance. In experiment 2, adult rats were given, for 9 weeks, a commercial rat diet supplemented with hydrochloric acid at levels up to 1250 mmol.kg-1 dry matter. Food intake and liveweight gain were not affected by hydrochloric acid concentration up to 625 mmole but at 938 mmol.kg-1 they were considerably reduced and there was 100% mortality of the rats. In experiment 3, weanling rats were given, for 12 weeks, a commercial rat diet supplemented with hydrochloric or lactic acid each at 300, 600 and 900 mmol.kg-1 dry matter. Lactic acid at the three levels and hydrochloric acid at the two lower levels did not affect food intake or live weight gain and had only a slight effect on blood acid-base balance. At a dietary concentration of 900 mmol.kg-1 dry matter, hydrochloric acid decreased food intake, induced a mild degree of metabolic acidosis and resulted in 30% mortality of the rats. In the three experiments, the acid treatments dnot directly affect the length or composition of the femur of the rats."}
{"id": "PMID:19811", "title": "The effect of fatigue on resident performance.", "content": "Fourteen rested and fatigued residents read a set of 25 test radiographs on two separate occasions approximately one month apart. The radiographs were made with partial chest phantom using pulmonary nodules as test objects. Seven rested and 7 fatigued residents read the radiographs, and a month later the order of fatigue was reversed. Fatigued residents had worked a minimum of 15 consecutive hours before their interpretations. Performance did not deteriorate with fatigue, and the nodule detection rate was almost identical on both occasions.", "contents": "The effect of fatigue on resident performance. Fourteen rested and fatigued residents read a set of 25 test radiographs on two separate occasions approximately one month apart. The radiographs were made with partial chest phantom using pulmonary nodules as test objects. Seven rested and 7 fatigued residents read the radiographs, and a month later the order of fatigue was reversed. Fatigued residents had worked a minimum of 15 consecutive hours before their interpretations. Performance did not deteriorate with fatigue, and the nodule detection rate was almost identical on both occasions."}
{"id": "PMID:19812", "title": "Prostaglandin E1 modifies nerve conduction and interferes with local anaesthetic action.", "content": "Prostaglandin E1 (PGE1) altered both the amplitude and conduction velocity of the compound action potential in frog sciatic nerve. Concentrations up to 1 ng/ml increased both amplitude and conduction velocity but at higher concentrations both effects were reversed. Procaine, chloroquine, indomethacin and SC19220 all reduced action potential amplitude and conduction velocity. These local anaesthetic type actions could be partially or completely prevented by PGE1.", "contents": "Prostaglandin E1 modifies nerve conduction and interferes with local anaesthetic action. Prostaglandin E1 (PGE1) altered both the amplitude and conduction velocity of the compound action potential in frog sciatic nerve. Concentrations up to 1 ng/ml increased both amplitude and conduction velocity but at higher concentrations both effects were reversed. Procaine, chloroquine, indomethacin and SC19220 all reduced action potential amplitude and conduction velocity. These local anaesthetic type actions could be partially or completely prevented by PGE1."}
{"id": "PMID:19813", "title": "On the structure of slow reacting substance of anaphylaxis: evidence of biosynthesis from arachidonic acid.", "content": "The mononuclear cells in peritoneal washings from normal rats can be induced to produce large amounts of slow reacting substance of anaphylaxis by incubation with 10 mM cysteine in the presence of the calcium ionophore A-23187. This production of slow reacting substance could be inhibited by the addition of non-steroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and flurbiprofen, Furthermore, mediator production was inhibited by eicosatetraynoic acid, the substrate analog of arachidonic acid, and by 9,11-azoprosta-5, 13-dienoic acid (AZO analog 1), a structural analog of the prostaglandin endoperoxide, PGH2, which known to inhibit thromboxane synthesis. Relatively high concentrations of hydrocortisone acetate inhibited mediator production; this inhibition could be partly reversed by the addition of arachidonic acid or to a lesser extent by eicosatrienoic acid. Preliminary results suggest that a  small fraction of the 3H-labled arachidonic acid which was taken up by these cells in vitro was associated with slow reacting substance. We postulate that slow reacting substance of anaphylaxis may be derived from a prostaglandin endoperoxide which is formed during the oxidation of arachidonic acid by the prostaglandin fatty acid cyclooxygenase.", "contents": "On the structure of slow reacting substance of anaphylaxis: evidence of biosynthesis from arachidonic acid. The mononuclear cells in peritoneal washings from normal rats can be induced to produce large amounts of slow reacting substance of anaphylaxis by incubation with 10 mM cysteine in the presence of the calcium ionophore A-23187. This production of slow reacting substance could be inhibited by the addition of non-steroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and flurbiprofen, Furthermore, mediator production was inhibited by eicosatetraynoic acid, the substrate analog of arachidonic acid, and by 9,11-azoprosta-5, 13-dienoic acid (AZO analog 1), a structural analog of the prostaglandin endoperoxide, PGH2, which known to inhibit thromboxane synthesis. Relatively high concentrations of hydrocortisone acetate inhibited mediator production; this inhibition could be partly reversed by the addition of arachidonic acid or to a lesser extent by eicosatrienoic acid. Preliminary results suggest that a  small fraction of the 3H-labled arachidonic acid which was taken up by these cells in vitro was associated with slow reacting substance. We postulate that slow reacting substance of anaphylaxis may be derived from a prostaglandin endoperoxide which is formed during the oxidation of arachidonic acid by the prostaglandin fatty acid cyclooxygenase."}
{"id": "PMID:19814", "title": "The TcO4-binding to human serum albumin --the stoichiometry and characteristics of the binding equilibrium.", "content": "The stoichiometry and the characteristics of the TcO4-binding equilibrium to human serum albumin were investigated by the use of 99TcO4-. Based on the Scatchard plots, the number of binding sites and the association constants were obtained at pH 7.38,6.04, 5.10, 4.18, 2.80 and 0.65, respectively. From the parameters at pH 7.38, it was estimated that 64% of TcO4- added was bounded to human serum albumin under physiological condition. Variance in the values at pH 7.38, 6.04 and 5.10 shows that these bindings are stabilized by electrostatic forces. Below pH 4.18, the number of binding sites increased and the association constants constants diminished. These phenomena may be attributed to the conformation change of human serum albumin.", "contents": "The TcO4-binding to human serum albumin --the stoichiometry and characteristics of the binding equilibrium. The stoichiometry and the characteristics of the TcO4-binding equilibrium to human serum albumin were investigated by the use of 99TcO4-. Based on the Scatchard plots, the number of binding sites and the association constants were obtained at pH 7.38,6.04, 5.10, 4.18, 2.80 and 0.65, respectively. From the parameters at pH 7.38, it was estimated that 64% of TcO4- added was bounded to human serum albumin under physiological condition. Variance in the values at pH 7.38, 6.04 and 5.10 shows that these bindings are stabilized by electrostatic forces. Below pH 4.18, the number of binding sites increased and the association constants constants diminished. These phenomena may be attributed to the conformation change of human serum albumin."}
{"id": "PMID:19817", "title": "[Effect of methionine sulfone on the growth of Citrobacter intermedius C3 (author's transl)].", "content": "Specific activity of glutamate dehydrogenase (GD) and glutamate synthase (GtS) has been determined in the wild strain C3 and on a non excreting pro- mutant strain. Methionine sulfone shows inhibitory effects on their growth. The addition of alpha-ketoglutarate to the medium prevents the inhibitory effect and increases the GtS specific activity in both strains. The physiological effect of methionine sulfone and its suppression by alpha-ketoglutarate is discussed.", "contents": "[Effect of methionine sulfone on the growth of Citrobacter intermedius C3 (author's transl)]. Specific activity of glutamate dehydrogenase (GD) and glutamate synthase (GtS) has been determined in the wild strain C3 and on a non excreting pro- mutant strain. Methionine sulfone shows inhibitory effects on their growth. The addition of alpha-ketoglutarate to the medium prevents the inhibitory effect and increases the GtS specific activity in both strains. The physiological effect of methionine sulfone and its suppression by alpha-ketoglutarate is discussed."}
{"id": "PMID:19821", "title": "Comparative antisecretory activity of several drugs in the gastric fistula squirrel monkey and rat.", "content": "A series of known antisecretory compounds, including glycopyrrolate, clonidine, propantheline bromide, CMN 131 (2-pyridylthiocetamide), and desmethylimipramine (DMI) were tested in the gastric fistula rat and monkey. The order of potency for inhibiting acid output was similar in both species. A general similarity exists in the responsiveness of the rat and monkey to gastric antisecretory agents. These data support the use of the squirrel monkey for assessment of gastric antisecretory activity.", "contents": "Comparative antisecretory activity of several drugs in the gastric fistula squirrel monkey and rat. A series of known antisecretory compounds, including glycopyrrolate, clonidine, propantheline bromide, CMN 131 (2-pyridylthiocetamide), and desmethylimipramine (DMI) were tested in the gastric fistula rat and monkey. The order of potency for inhibiting acid output was similar in both species. A general similarity exists in the responsiveness of the rat and monkey to gastric antisecretory agents. These data support the use of the squirrel monkey for assessment of gastric antisecretory activity."}
{"id": "PMID:19822", "title": "The effect of pH on stereospecific opiate binding to mouse brain membranes.", "content": "High-affinity, in vitro stereospecific binding of 3H-di-hydromorphine or 3H-naloxone to brain membranes shows a marked dependence on pH; maximal binding, observed at pH 7.5-8.0, is abruptly and reversibly reduced as the pH is lowered, with the binding half-maximal at about pH 6.8. A similar pH dependence of stereospecific binding is observed with the quaternary agonist N-methyl morphine, but non-specific 3H-di-hydromorphine of 3H-naloxone binding (that not displaced by a 100-fold excess of unlabelled levorphanol) shows only a slight decrease in this pH range. Binding of agonist and antagonist at pH 6.8 show the same differences with respect to trypsin sensitivity and to the effects of Na+ and Mn++ ions that are seen at pH 8.0. It is concluded that the ability of low pH to reduce stereospecific binding is due to protonation of a membrane-bound site, and that this site is probably the anionic site of the opiate receptor. Of the four anionic groups commonly found in biological membranes, only phosphate exhibits a pK close to that of this effect. Taken with other evidence, the results suggest that the opiate receptor may be a phosphoprotein.", "contents": "The effect of pH on stereospecific opiate binding to mouse brain membranes. High-affinity, in vitro stereospecific binding of 3H-di-hydromorphine or 3H-naloxone to brain membranes shows a marked dependence on pH; maximal binding, observed at pH 7.5-8.0, is abruptly and reversibly reduced as the pH is lowered, with the binding half-maximal at about pH 6.8. A similar pH dependence of stereospecific binding is observed with the quaternary agonist N-methyl morphine, but non-specific 3H-di-hydromorphine of 3H-naloxone binding (that not displaced by a 100-fold excess of unlabelled levorphanol) shows only a slight decrease in this pH range. Binding of agonist and antagonist at pH 6.8 show the same differences with respect to trypsin sensitivity and to the effects of Na+ and Mn++ ions that are seen at pH 8.0. It is concluded that the ability of low pH to reduce stereospecific binding is due to protonation of a membrane-bound site, and that this site is probably the anionic site of the opiate receptor. Of the four anionic groups commonly found in biological membranes, only phosphate exhibits a pK close to that of this effect. Taken with other evidence, the results suggest that the opiate receptor may be a phosphoprotein."}
{"id": "PMID:19818", "title": "[Use of chemical disinfectants in alcoholic fermentation of must of sugar cane molasses].", "content": "The use of hexaclorophene as desinfectant for alcoholic fermentation was studied. Its effect upon alcoholic yield and acidity levels of \"beers\" and \"spirit\" was observed. The optimal concentration of hexaclorophene in fermentation broth was found to be 4%.", "contents": "[Use of chemical disinfectants in alcoholic fermentation of must of sugar cane molasses]. The use of hexaclorophene as desinfectant for alcoholic fermentation was studied. Its effect upon alcoholic yield and acidity levels of \"beers\" and \"spirit\" was observed. The optimal concentration of hexaclorophene in fermentation broth was found to be 4%."}
{"id": "PMID:19823", "title": "Red cell lysis coupled to the peroxidation of liver microsomal lipids. Compartmentalization of the hemolytic system.", "content": "As a contribution to the understanding of the mechanisms by which addition of erythrocytes to liver microsomes incubated in the NADPH dependent system results in hemolysis, experiments are presented here in which the system containing actively peroxidizing microsomes was separated from the system containing the red blood cells by a dialysis membrane. It is shown that when liver microsomes were incubated with NADPH, lipid peroxidation, as measured by the formation of malonic dialdehyde (MDA), rapidly took place. The MDA concentration tended to equilibrate across the dialysis membrane. After a lag phase of 60 min, lysis of erythrocytes contained in the dialysis tube, started. It reached its maximal level (more than 80%) at 110 min of incubation. These results strongly suggest the possibility that toxic products originating during the course of lipid peroxidation induce pathological effect at distant loci. Furthermore, the accomplishment of a compartmentalization of the two systems involved in the reaction, may offer an approach to the recognition of the toxic factors.", "contents": "Red cell lysis coupled to the peroxidation of liver microsomal lipids. Compartmentalization of the hemolytic system. As a contribution to the understanding of the mechanisms by which addition of erythrocytes to liver microsomes incubated in the NADPH dependent system results in hemolysis, experiments are presented here in which the system containing actively peroxidizing microsomes was separated from the system containing the red blood cells by a dialysis membrane. It is shown that when liver microsomes were incubated with NADPH, lipid peroxidation, as measured by the formation of malonic dialdehyde (MDA), rapidly took place. The MDA concentration tended to equilibrate across the dialysis membrane. After a lag phase of 60 min, lysis of erythrocytes contained in the dialysis tube, started. It reached its maximal level (more than 80%) at 110 min of incubation. These results strongly suggest the possibility that toxic products originating during the course of lipid peroxidation induce pathological effect at distant loci. Furthermore, the accomplishment of a compartmentalization of the two systems involved in the reaction, may offer an approach to the recognition of the toxic factors."}
{"id": "PMID:19819", "title": "[Isolation of proteins in coconut water].", "content": "The isolation of protein fractions in cocont water was achieved by precipitation with controlled pH variation obtaining three isolates at pH 8,5, 10,5, and 11,5. By comparing each of these isolates with proteins of coconut milk, a similarity between properties of the first two isolates of the water - pH 8,5, 10,5--and those of coconut serum proteins -- glutelin and prolamin was observed. The third isolate is entirely absent from the milk, when coconut water is not used in the second pressing to obtain the milk.", "contents": "[Isolation of proteins in coconut water]. The isolation of protein fractions in cocont water was achieved by precipitation with controlled pH variation obtaining three isolates at pH 8,5, 10,5, and 11,5. By comparing each of these isolates with proteins of coconut milk, a similarity between properties of the first two isolates of the water - pH 8,5, 10,5--and those of coconut serum proteins -- glutelin and prolamin was observed. The third isolate is entirely absent from the milk, when coconut water is not used in the second pressing to obtain the milk."}
{"id": "PMID:19824", "title": "Metal ion catalyzed oxidation of the antibiotic rifampicin.", "content": "The metal ions Cu++, Mn++ and Co+++, but not Ca++, Fe+++, K+, La+++, Mg++, Na+, Sr++ or Zn++ catalyzed the oxidation of rifampicin from the naphthohydroquinone to the naphthoquinone form. This reaction was pH dependent, and occurred at neutral or basic pH more rapidly than at acidic pH. Mn++ catalyzed the most rapid oxidation, followed by Cu++ and then Co+++. Rifampicin oxidation was metal ion dependent and complete oxidation occurred at metal ion concentrations below stoichiometric values. Initial rate studies suggest that the oxidation mechanism is complex.", "contents": "Metal ion catalyzed oxidation of the antibiotic rifampicin. The metal ions Cu++, Mn++ and Co+++, but not Ca++, Fe+++, K+, La+++, Mg++, Na+, Sr++ or Zn++ catalyzed the oxidation of rifampicin from the naphthohydroquinone to the naphthoquinone form. This reaction was pH dependent, and occurred at neutral or basic pH more rapidly than at acidic pH. Mn++ catalyzed the most rapid oxidation, followed by Cu++ and then Co+++. Rifampicin oxidation was metal ion dependent and complete oxidation occurred at metal ion concentrations below stoichiometric values. Initial rate studies suggest that the oxidation mechanism is complex."}
{"id": "PMID:19825", "title": "Regulation of intracellular cyclic GMP and cyclic AMP levels in mouse lung fragments by disodium cromoglycate, beta-adrenergic agonists, cholinergic activators, and histamine.", "content": "The effects of adrenergic and cholinergic agents as well as the effects of disodium cromoglycate (DSCG) on the levels of cyclic AMP and cyclic GMP in mouse lung fragments were studied. Levels of cyclic AMP were enhanced by two of the known beta-adrenergic agonists, epinephrine and isoproterenol. This increase was abolished by propanolol, a recognized beta-adrenergic antagonist. Disodium cromoglycate, a proposed inhibitor of phosphodiesterases, alone caused a slight, significant increase in cyclic AMP. However, in the presence of epinephrine, levels of cyclic AMP were potentiated by DSCG. DSCG behaves, therefore, as a typical cyclic AMP phosphodiesterase inhibitor. Cyclic GMP levels were increased by carbachol, acetylcholine, and the phosphodiesterase inhibitor, aminophylline, but not by DSCG, or beta-adrenergic agonists.", "contents": "Regulation of intracellular cyclic GMP and cyclic AMP levels in mouse lung fragments by disodium cromoglycate, beta-adrenergic agonists, cholinergic activators, and histamine. The effects of adrenergic and cholinergic agents as well as the effects of disodium cromoglycate (DSCG) on the levels of cyclic AMP and cyclic GMP in mouse lung fragments were studied. Levels of cyclic AMP were enhanced by two of the known beta-adrenergic agonists, epinephrine and isoproterenol. This increase was abolished by propanolol, a recognized beta-adrenergic antagonist. Disodium cromoglycate, a proposed inhibitor of phosphodiesterases, alone caused a slight, significant increase in cyclic AMP. However, in the presence of epinephrine, levels of cyclic AMP were potentiated by DSCG. DSCG behaves, therefore, as a typical cyclic AMP phosphodiesterase inhibitor. Cyclic GMP levels were increased by carbachol, acetylcholine, and the phosphodiesterase inhibitor, aminophylline, but not by DSCG, or beta-adrenergic agonists."}
{"id": "PMID:19826", "title": "Failure to observe pathology in the rat following chronic dosing with acetaminophen and acetylsalicylic acid.", "content": "Male Wistar rats were dosed daily by gavage for 200 days with either (1) aspirin, 200 mg/kg; (2) acetaminophen, 200 mg/kg; (3) aspirin and acetaminophen, 200 mg/kg of each; (4) aspirin and acetaminophen, 100 mg/kg of each or (5) vehicle alone. None of the treatments produced any marked signs of toxicity and no drug related deaths were observed. The full dose combination (3) did significantly reduce the weight compared to the control group (5). When urinary lactic dehydrogenase and alkaline phosphatase were measured, all treatments caused some increase in activity but those containing aspirin had the greatest effect. Urinary pH and osmolarity were not effected by the treatments. Complete pathological examination of the animals failed to detect any significant changes when compared to the controls. It is concluded that there is no evidence of a toxic interaction between aspirin and acetaminophen in the rat.", "contents": "Failure to observe pathology in the rat following chronic dosing with acetaminophen and acetylsalicylic acid. Male Wistar rats were dosed daily by gavage for 200 days with either (1) aspirin, 200 mg/kg; (2) acetaminophen, 200 mg/kg; (3) aspirin and acetaminophen, 200 mg/kg of each; (4) aspirin and acetaminophen, 100 mg/kg of each or (5) vehicle alone. None of the treatments produced any marked signs of toxicity and no drug related deaths were observed. The full dose combination (3) did significantly reduce the weight compared to the control group (5). When urinary lactic dehydrogenase and alkaline phosphatase were measured, all treatments caused some increase in activity but those containing aspirin had the greatest effect. Urinary pH and osmolarity were not effected by the treatments. Complete pathological examination of the animals failed to detect any significant changes when compared to the controls. It is concluded that there is no evidence of a toxic interaction between aspirin and acetaminophen in the rat."}
{"id": "PMID:19827", "title": "Influence of catecholamine-derived alkaloids and beta-adrenergic blocking agents on stereospecific binding of 3H-naloxone.", "content": "Alkaloids containing a catecholamine moiety, viz., tetrahydroisoquinolines and tetrahydroprotoberberines, and a group of beta-adrenergic blocking agents were examined for their effects on the binding of tritiated naloxone by rat brain homogenate. The stereospecific binding of the opiate antagonist was weakly inhibited by the catecholamine-derived alkaloids. The concentration of alkaloids producing 50% inhibition of binding ranged from 0.06 to 0.37 mM. The inhibitory effects of the beta-adrenergic blocking agents appear to parallel their reported relative local anesthetic actions.", "contents": "Influence of catecholamine-derived alkaloids and beta-adrenergic blocking agents on stereospecific binding of 3H-naloxone. Alkaloids containing a catecholamine moiety, viz., tetrahydroisoquinolines and tetrahydroprotoberberines, and a group of beta-adrenergic blocking agents were examined for their effects on the binding of tritiated naloxone by rat brain homogenate. The stereospecific binding of the opiate antagonist was weakly inhibited by the catecholamine-derived alkaloids. The concentration of alkaloids producing 50% inhibition of binding ranged from 0.06 to 0.37 mM. The inhibitory effects of the beta-adrenergic blocking agents appear to parallel their reported relative local anesthetic actions."}
{"id": "PMID:19828", "title": "Comparison of the effects of several selective B2-receptor agonists on bronchomotor function in vitro.", "content": "Three selective B2-adrenergic stimulants were studied for their effect on the resting tone and on reversing acetylcholine (ACh)-induced bronchoconstriction in the intrapulmonary airways of rats in vitro. Neither 1-(3,5-dihydroxyphenyl)-2-[(1-[4-hydroxybenzyl]-ethyl)-amino]-ethanol-hydrobromide (Fenoterol) nor 2-tert-butylamino-1-(3,5-dihydroxyphenyl)-ethanol-sulphate (Terbutaline) had an effect on the resting tone. 4-Amino-3,5-dichlor-alpha-[(tert-butylamino)-methyl1-benzylalcohol-hydrochloride (NAB 365) caused a significant increase in the bronchial luminal diameter from control in the resting state at concentraions above 10(-5) g/ml. Only NAB 365 was effective in reversing ACh-induced bronchoconstriction in concentrations above 10(-6) g/ml. Terbutaline and Fenoterol reversed the ACh-induced bronchoconstriction only after the alpha-receptors had been blocked by phentolamine (10(-5)-10(-4)g/ml).", "contents": "Comparison of the effects of several selective B2-receptor agonists on bronchomotor function in vitro. Three selective B2-adrenergic stimulants were studied for their effect on the resting tone and on reversing acetylcholine (ACh)-induced bronchoconstriction in the intrapulmonary airways of rats in vitro. Neither 1-(3,5-dihydroxyphenyl)-2-[(1-[4-hydroxybenzyl]-ethyl)-amino]-ethanol-hydrobromide (Fenoterol) nor 2-tert-butylamino-1-(3,5-dihydroxyphenyl)-ethanol-sulphate (Terbutaline) had an effect on the resting tone. 4-Amino-3,5-dichlor-alpha-[(tert-butylamino)-methyl1-benzylalcohol-hydrochloride (NAB 365) caused a significant increase in the bronchial luminal diameter from control in the resting state at concentraions above 10(-5) g/ml. Only NAB 365 was effective in reversing ACh-induced bronchoconstriction in concentrations above 10(-6) g/ml. Terbutaline and Fenoterol reversed the ACh-induced bronchoconstriction only after the alpha-receptors had been blocked by phentolamine (10(-5)-10(-4)g/ml)."}
{"id": "PMID:19829", "title": "[Effect of beta-adrenergic stimulation on the closing volume in normal subjects (author's transl].", "content": "In 12 normal subjets we studies the effects of beta-adrenergic stimulation (Salbutamol, 500 microgram inhaled) on the closing volume (CV) and the closing capacity and on the ratios of these indexes to the vital capacity (VC) and the total lung capacity, respectively. CV and CV/VC % increased in ten subjects wereas it decreased in two subjects. On an average, the changes  were small but significant (p less than 0.01) and could be duplicated in four subjects. Similar studies have yielded variable results. The reasons for those variation could be attributed either to technical or/and individual differences in the resulting effect of beta stimulation on respiratory mechanics.", "contents": "[Effect of beta-adrenergic stimulation on the closing volume in normal subjects (author's transl]. In 12 normal subjets we studies the effects of beta-adrenergic stimulation (Salbutamol, 500 microgram inhaled) on the closing volume (CV) and the closing capacity and on the ratios of these indexes to the vital capacity (VC) and the total lung capacity, respectively. CV and CV/VC % increased in ten subjects wereas it decreased in two subjects. On an average, the changes  were small but significant (p less than 0.01) and could be duplicated in four subjects. Similar studies have yielded variable results. The reasons for those variation could be attributed either to technical or/and individual differences in the resulting effect of beta stimulation on respiratory mechanics."}
{"id": "PMID:19830", "title": "Blood respiratory properties of Bison bison.", "content": "The respiratory properties and basic hematology of blood from seven adult bison and one calf were determined. Average oxygen-carrying capacity was 22.2 ml/100 ml blood from adults and 17.0 in calf blood; hemoglobin averaged 17.1 g/100 ml in adults and 13.6 in the calf. Half saturation of the blood occurred at 32mm Hg Po2 at pH 7.40 and 37 degrees C. The average Bohr effect was -0.40. Erythrocytes numbered 8.6 X 10(6)/mm3 and were 52 micron 3 in mean volume. Adult and calf cells differed in mean cell hemoglobin, adults 19.9 pg/cell vs 15.9 in the calf, and this difference evidently caused differences in Haldane effect, standard bicarbonate, and buffering capacity. Bison are capable of prolonged running. Two features of the blood that promote this capacity are its comparatively great oxygen-carrying capacity and low oxygen affinity.", "contents": "Blood respiratory properties of Bison bison. The respiratory properties and basic hematology of blood from seven adult bison and one calf were determined. Average oxygen-carrying capacity was 22.2 ml/100 ml blood from adults and 17.0 in calf blood; hemoglobin averaged 17.1 g/100 ml in adults and 13.6 in the calf. Half saturation of the blood occurred at 32mm Hg Po2 at pH 7.40 and 37 degrees C. The average Bohr effect was -0.40. Erythrocytes numbered 8.6 X 10(6)/mm3 and were 52 micron 3 in mean volume. Adult and calf cells differed in mean cell hemoglobin, adults 19.9 pg/cell vs 15.9 in the calf, and this difference evidently caused differences in Haldane effect, standard bicarbonate, and buffering capacity. Bison are capable of prolonged running. Two features of the blood that promote this capacity are its comparatively great oxygen-carrying capacity and low oxygen affinity."}
{"id": "PMID:19831", "title": "Arterial hydrogen ion versus CO2 on depth and rate of breathing in decerebrate cats.", "content": "Arterial blood hydrogen ion concentration (Ha+) was altered over the range of 25 to 110 nM (pH 7.60 to 6.96) by slow intravenous infusion of 1.0 N NaHCO3 or 0.5 N HC1 at controlled levels of Paco2in unanesthetized decerebrate cats. Respiratory f varied as a single function of Vt irrespective of a lterations in Paco2 and Ha+ even after interruption of the carotid sinus nerves. The dependence of f upon Vt was abolished by vagotomy. However, Vt continued to respond to changes in Ha+ over its entire range after combined section of the vagus and carotid sinus nerves. In all statxceeded by 5 to 10 times the delta Vt/delta Ha+ response to acid or bicarbonate infused under isocapnic control. Increases and decreases of ha+ caused downward and upward shifts, respectively, in the operating setpoint of the CO2 regulation system.", "contents": "Arterial hydrogen ion versus CO2 on depth and rate of breathing in decerebrate cats. Arterial blood hydrogen ion concentration (Ha+) was altered over the range of 25 to 110 nM (pH 7.60 to 6.96) by slow intravenous infusion of 1.0 N NaHCO3 or 0.5 N HC1 at controlled levels of Paco2in unanesthetized decerebrate cats. Respiratory f varied as a single function of Vt irrespective of a lterations in Paco2 and Ha+ even after interruption of the carotid sinus nerves. The dependence of f upon Vt was abolished by vagotomy. However, Vt continued to respond to changes in Ha+ over its entire range after combined section of the vagus and carotid sinus nerves. In all statxceeded by 5 to 10 times the delta Vt/delta Ha+ response to acid or bicarbonate infused under isocapnic control. Increases and decreases of ha+ caused downward and upward shifts, respectively, in the operating setpoint of the CO2 regulation system."}
{"id": "PMID:19832", "title": "Thermorespiratory responses of shorn and unshorn sheep to mild heat stress.", "content": "Three 3-year-old ewes with surgically exteriorized carotid loops were twice exposed to ambient temperatures (Ta) of 25, 30, 35 and 40 C (at constant 40% relative humidity) for 120 min in the presence (6.6 cm) and absence (less than 0.3 cm) of fleece. Thermoregulatory responses were evaluated during the last 30 min of each exposure by measurements of rectal (Tre), 6 skin surface temperatures (Ts), respiratory frequency (f), oxygen consumption (Vo2) and respiratory evaporative heat (Er); arterial blood samples were analyzed for pH, Pco2 and HCO-3 concentration. Both shorn and unshorn sheep exhibited a progressive increase in f, Er and Ts as Ta was elevated, with the unshorn group showing a higher Er than the shorn sheep at each Ta without a significant change in heat production. Er was found to be the principal avenue of heat loss, accounting for as much as 59% of the total in the shorn sheep compared to65% for the unshorn sheep. Increases in Er were accompanied by a decline in the arterial Pco2 which was linearly related to the Ta in both shorn and unshorn sheep. These data suggest that in defending against hyperthermia, sheep appear unable to increase Er without a concurrent elevation in Va at nearly allstages of acute heat stress.", "contents": "Thermorespiratory responses of shorn and unshorn sheep to mild heat stress. Three 3-year-old ewes with surgically exteriorized carotid loops were twice exposed to ambient temperatures (Ta) of 25, 30, 35 and 40 C (at constant 40% relative humidity) for 120 min in the presence (6.6 cm) and absence (less than 0.3 cm) of fleece. Thermoregulatory responses were evaluated during the last 30 min of each exposure by measurements of rectal (Tre), 6 skin surface temperatures (Ts), respiratory frequency (f), oxygen consumption (Vo2) and respiratory evaporative heat (Er); arterial blood samples were analyzed for pH, Pco2 and HCO-3 concentration. Both shorn and unshorn sheep exhibited a progressive increase in f, Er and Ts as Ta was elevated, with the unshorn group showing a higher Er than the shorn sheep at each Ta without a significant change in heat production. Er was found to be the principal avenue of heat loss, accounting for as much as 59% of the total in the shorn sheep compared to65% for the unshorn sheep. Increases in Er were accompanied by a decline in the arterial Pco2 which was linearly related to the Ta in both shorn and unshorn sheep. These data suggest that in defending against hyperthermia, sheep appear unable to increase Er without a concurrent elevation in Va at nearly allstages of acute heat stress."}
{"id": "PMID:19833", "title": "Effect of simulated altitude on blood gas transport in the pigeon.", "content": "Unacclimated pigeons were exposed to various simulated altitudes. Arterial and mixed venous blood gas levels were measured. At the highest altitude 9150m (Pb = 235 mm Hg) a remarkable degree of alkalosis was tolerated for several hours without ill effecrtant factor in the bird's ability to survive such altitudes.", "contents": "Effect of simulated altitude on blood gas transport in the pigeon. Unacclimated pigeons were exposed to various simulated altitudes. Arterial and mixed venous blood gas levels were measured. At the highest altitude 9150m (Pb = 235 mm Hg) a remarkable degree of alkalosis was tolerated for several hours without ill effecrtant factor in the bird's ability to survive such altitudes."}
{"id": "PMID:19841", "title": "Calcium fluoride formation on enamel and its influence on uptake of fluoride in the apatitic lattice.", "content": "Human dental enamel was exposed to a pH 4 buffer containing 150 parts/10(6) fluoride. It was found that due to the arising degrees of saturation with respect to calcium fluoride and apatites, surface enamel dissolved coincident with a formation of calcium fluoride. The calcium fluoride redissolved while it kept the liquid saturated with respect to this salt. During this second period, fluorapatite was formed while hydroxyapatite dissolved. Finally, all calcium fluoride was dissolved and the unreacted fluoride was taken up in the apatitic lattice. The results are discussed with reference to the conditions of the oral cavity and enamel solubility experiments.", "contents": "Calcium fluoride formation on enamel and its influence on uptake of fluoride in the apatitic lattice. Human dental enamel was exposed to a pH 4 buffer containing 150 parts/10(6) fluoride. It was found that due to the arising degrees of saturation with respect to calcium fluoride and apatites, surface enamel dissolved coincident with a formation of calcium fluoride. The calcium fluoride redissolved while it kept the liquid saturated with respect to this salt. During this second period, fluorapatite was formed while hydroxyapatite dissolved. Finally, all calcium fluoride was dissolved and the unreacted fluoride was taken up in the apatitic lattice. The results are discussed with reference to the conditions of the oral cavity and enamel solubility experiments."}
{"id": "PMID:19842", "title": "Standardization of the nitroblue tetrazolium test. Influence of pH, dye concentration and sample storage.", "content": "The influence of pH, dye concentration and sample storage on the histochemical nitroblue tetrazolium (NBT) test in 45 patients with acute bacterial infections and 51 healthy individuals has been examined. Even minor deviations in pH and NBT dye concentration markedly influenced the reduction of NBT to formazan by patient and control neutrophils, and the differentiation between results in these groups was optimal at pH 7.2 and a concentration of 0.05% NBT in the final blood-NBT mixture. Storage of heparinized blood samples for more than 2 hours at 21 degrees C and for more than 6 hours at 4 degrees C is not recommended due to overlap between results in patients and controls. The error involved in counting of NBT-positive neutrophils accounted for the major discrepancies tests in patients and controls and in tests performed on different days. The reproducibility of the endotoxin stimulated test was inferior to that of the unstimulated test.", "contents": "Standardization of the nitroblue tetrazolium test. Influence of pH, dye concentration and sample storage. The influence of pH, dye concentration and sample storage on the histochemical nitroblue tetrazolium (NBT) test in 45 patients with acute bacterial infections and 51 healthy individuals has been examined. Even minor deviations in pH and NBT dye concentration markedly influenced the reduction of NBT to formazan by patient and control neutrophils, and the differentiation between results in these groups was optimal at pH 7.2 and a concentration of 0.05% NBT in the final blood-NBT mixture. Storage of heparinized blood samples for more than 2 hours at 21 degrees C and for more than 6 hours at 4 degrees C is not recommended due to overlap between results in patients and controls. The error involved in counting of NBT-positive neutrophils accounted for the major discrepancies tests in patients and controls and in tests performed on different days. The reproducibility of the endotoxin stimulated test was inferior to that of the unstimulated test."}
{"id": "PMID:19839", "title": "[Study of a new hypnotic drug: Ro 5-4200 (flunitrazepam)].", "content": "The Authors carried out a clinical study of a new benzodiazepinic derivative (Ro 5-4200) presenting hypnotic properties particularly \"interesting\". The results emerged from this study confirmed the hypnotic efficacy of the preparation also in case of insomnia of a certain seriousness, as well as its excellent tolerance.", "contents": "[Study of a new hypnotic drug: Ro 5-4200 (flunitrazepam)]. The Authors carried out a clinical study of a new benzodiazepinic derivative (Ro 5-4200) presenting hypnotic properties particularly \"interesting\". The results emerged from this study confirmed the hypnotic efficacy of the preparation also in case of insomnia of a certain seriousness, as well as its excellent tolerance."}
{"id": "PMID:19843", "title": "Eschaemia during arterial reconstructive surgery. Biochemical changes as reflected in popliteal vein samples.", "content": "Blood gases, electrolytes, metabolites and enzymes were studied in the venous effluate from the leg and in the systemic blood of 8 patients suffering from obliterating arteriosclerosis, during and after reconstructive arterial surgery. The common femoral artery was clamped for 50 to 180 min. Marked hypoxia and acidosis, together with a rise in lactate, phosphate and creatinine concentrations were found in the popliteal vein samples. Changes in the electrolyte concentrations were also observed. The rises in K+ and Mg++ were most pronounced. None of the changes wre correlated to the occlusion time and only small inter-individual variations were recorded. Only minor systemic change occurred after restoration of blood flow. The maximum postoperative CPK-activity, however, was closely correlated to the occlusion time, but judging by the level of this activity the actual muscular damage caused by the ischaemia was moderate, even after prolonged arterial clamping.", "contents": "Eschaemia during arterial reconstructive surgery. Biochemical changes as reflected in popliteal vein samples. Blood gases, electrolytes, metabolites and enzymes were studied in the venous effluate from the leg and in the systemic blood of 8 patients suffering from obliterating arteriosclerosis, during and after reconstructive arterial surgery. The common femoral artery was clamped for 50 to 180 min. Marked hypoxia and acidosis, together with a rise in lactate, phosphate and creatinine concentrations were found in the popliteal vein samples. Changes in the electrolyte concentrations were also observed. The rises in K+ and Mg++ were most pronounced. None of the changes wre correlated to the occlusion time and only small inter-individual variations were recorded. Only minor systemic change occurred after restoration of blood flow. The maximum postoperative CPK-activity, however, was closely correlated to the occlusion time, but judging by the level of this activity the actual muscular damage caused by the ischaemia was moderate, even after prolonged arterial clamping."}
{"id": "PMID:19844", "title": "[Use of immunosuppressive agents in systemic diseases].", "content": "The use of immuno-suppressive agents in systemic diseases where the auto-immune origin is probable or certain is not yet based on definite physiopathological evidence. Therefore, it seems essential to use this treatment which has definite side effects only in cases where the progressive nature of the disease, renal complications or the incomplete or nil efficacy of less agressive treatments, leave no choice.", "contents": "[Use of immunosuppressive agents in systemic diseases]. The use of immuno-suppressive agents in systemic diseases where the auto-immune origin is probable or certain is not yet based on definite physiopathological evidence. Therefore, it seems essential to use this treatment which has definite side effects only in cases where the progressive nature of the disease, renal complications or the incomplete or nil efficacy of less agressive treatments, leave no choice."}
{"id": "PMID:19847", "title": "Demonstration of cryoprecipitable immune complexes in pneumococcal pneumonia.", "content": "Cold-insoluble protein complexes (cryoprecipitates) can be found in the serum in a variety of infectious diseases. We studied serum cryoprecipitates isolated from three patients with pneumococcal pneumonia by counterimmunoelectrophoresis (CEP) and immunofluorescent technics for the presence of immune complexes. The cryoprecipitates and supernatant serum were tested for pneumococcal capsular polysaccharide (PCP) by CEP at 37 C and 56 C with the appropriate controls. Antibodies against PCP in the cryoprecipitates and the supernatant serum were detected as follows. Streptococcus pneumoniae from each case was fixed onto slides. The slides were incubated with each cryoprecipitate and supernatant serum at 37 C, and further incubated with fluorescein isothiocyanate-conjugated antisera to human IgG, IgM, and IgA. The slides were examined with an immunofluorescent microscope. PCP was demonstrated in all of the cryoprecipitates. IgG antibodies against PCP were detected in all of the cryoprecipitates, while IgM antibodies were detected in Cases 1 and 2, and IgA antibodies in Case 1 only. Complement components of C3 and C4 also were demonstrated in the cryoprecipitates by CEP. These findings suggest that some patients with pneumococcal pneumonia have cryoprecipitable-immune complexes consisting of PCP and its antibodies.", "contents": "Demonstration of cryoprecipitable immune complexes in pneumococcal pneumonia. Cold-insoluble protein complexes (cryoprecipitates) can be found in the serum in a variety of infectious diseases. We studied serum cryoprecipitates isolated from three patients with pneumococcal pneumonia by counterimmunoelectrophoresis (CEP) and immunofluorescent technics for the presence of immune complexes. The cryoprecipitates and supernatant serum were tested for pneumococcal capsular polysaccharide (PCP) by CEP at 37 C and 56 C with the appropriate controls. Antibodies against PCP in the cryoprecipitates and the supernatant serum were detected as follows. Streptococcus pneumoniae from each case was fixed onto slides. The slides were incubated with each cryoprecipitate and supernatant serum at 37 C, and further incubated with fluorescein isothiocyanate-conjugated antisera to human IgG, IgM, and IgA. The slides were examined with an immunofluorescent microscope. PCP was demonstrated in all of the cryoprecipitates. IgG antibodies against PCP were detected in all of the cryoprecipitates, while IgM antibodies were detected in Cases 1 and 2, and IgA antibodies in Case 1 only. Complement components of C3 and C4 also were demonstrated in the cryoprecipitates by CEP. These findings suggest that some patients with pneumococcal pneumonia have cryoprecipitable-immune complexes consisting of PCP and its antibodies."}
{"id": "PMID:19845", "title": "[Detection of excessive chronic alcoholic consumption and control of withdrawal. Comparative study of respective values of the mean red-cell volume and serum gamma-glutamyl-transferase activity].", "content": "The routine detection of chronic alcoholism is necessary during any medical examination whether private or in hospital, or in occupational medicine. The practitionner now has available a simple reliable and cheap test. It consists of the serum estimation of gamma-glutamyl-transferase (gammaGT) and interpretation of the average red cell volume supplied by automatic counting of the red cell. Out of 120 chronic alcoholic subjects ; 67% has a gammaGT increased and 44% had macrocytosis. Under the influence of weaning, there was a rapid fall in gammaGT and a slower reduction in average red cell volume. gammaGT estimation was thus a more sensitive test than M.C.V. for the detection of chronic alcoholics and the control of withdrawal. Its association with the rise in immunoglobulin A-transferrin ratio which we have suggested permits the detection of almost all chronic alcoholics in the population studied.", "contents": "[Detection of excessive chronic alcoholic consumption and control of withdrawal. Comparative study of respective values of the mean red-cell volume and serum gamma-glutamyl-transferase activity]. The routine detection of chronic alcoholism is necessary during any medical examination whether private or in hospital, or in occupational medicine. The practitionner now has available a simple reliable and cheap test. It consists of the serum estimation of gamma-glutamyl-transferase (gammaGT) and interpretation of the average red cell volume supplied by automatic counting of the red cell. Out of 120 chronic alcoholic subjects ; 67% has a gammaGT increased and 44% had macrocytosis. Under the influence of weaning, there was a rapid fall in gammaGT and a slower reduction in average red cell volume. gammaGT estimation was thus a more sensitive test than M.C.V. for the detection of chronic alcoholics and the control of withdrawal. Its association with the rise in immunoglobulin A-transferrin ratio which we have suggested permits the detection of almost all chronic alcoholics in the population studied."}
{"id": "PMID:19850", "title": "Gastric volume and acidity at caesarean section.", "content": "The pulmonary acid aspiration (Mendelson's) syndrome may present after regurgitation and inhalation of acid gastric content during obstetric anesthesia. The stomach contents of 70 mothers were aspirated at caesarean section after pre-operative gastric 'emptying' and alkaline ingestion. The acidity of the gastric aspirate was analysed and volumes were measured. The patients were divided into 5 groups according to the time when gastric aspiration was carried out. A 'safe' gastric pH (pH greater than 3.5) was found in all patients up to 2 hours after antacid ingestion (groups 1-3). However, 2 1/2 hours after antacid ingestion (group 4y, 50% of patients had gastric volumes in excess of 25 ml and a pH of less than 3.5. We therefore recommend that, if general anaesthesia is to be induced or is in progress 2 hours after antacid therapy, the alkaline regimen should be resumed after repeated gastric aspiration.", "contents": "Gastric volume and acidity at caesarean section. The pulmonary acid aspiration (Mendelson's) syndrome may present after regurgitation and inhalation of acid gastric content during obstetric anesthesia. The stomach contents of 70 mothers were aspirated at caesarean section after pre-operative gastric 'emptying' and alkaline ingestion. The acidity of the gastric aspirate was analysed and volumes were measured. The patients were divided into 5 groups according to the time when gastric aspiration was carried out. A 'safe' gastric pH (pH greater than 3.5) was found in all patients up to 2 hours after antacid ingestion (groups 1-3). However, 2 1/2 hours after antacid ingestion (group 4y, 50% of patients had gastric volumes in excess of 25 ml and a pH of less than 3.5. We therefore recommend that, if general anaesthesia is to be induced or is in progress 2 hours after antacid therapy, the alkaline regimen should be resumed after repeated gastric aspiration."}
{"id": "PMID:19846", "title": "[Comparative study of a factor-VIII inhibitor in a non-hemophylic patient and in a patient with hemophylia A gravis].", "content": "In this study, we tried to make a comparison between the findings concerning two human strong anti Factor VIII inhibitors. In one case, the strong inhibitor appeared in an old man without any particular antecedant. In the second case, it occurred in a young hemophiliac A. We found in both cases that the inhibitor was a immunoglobulin G with light chain lambda. Its activity site is on the fragment AB. These anticoagulants have a inhibitory action against only the Factor VIII procoagulant fraction and have exclusively neutralising properties. The inhibitor present in the non hemophiliac patient has particularly great resistance to temperature and pH variations.", "contents": "[Comparative study of a factor-VIII inhibitor in a non-hemophylic patient and in a patient with hemophylia A gravis]. In this study, we tried to make a comparison between the findings concerning two human strong anti Factor VIII inhibitors. In one case, the strong inhibitor appeared in an old man without any particular antecedant. In the second case, it occurred in a young hemophiliac A. We found in both cases that the inhibitor was a immunoglobulin G with light chain lambda. Its activity site is on the fragment AB. These anticoagulants have a inhibitory action against only the Factor VIII procoagulant fraction and have exclusively neutralising properties. The inhibitor present in the non hemophiliac patient has particularly great resistance to temperature and pH variations."}
{"id": "PMID:19860", "title": "The conjugation of testosterone with horseradish peroxidase and a sensitive enzyme assay for the conjugate.", "content": "The formation of a horseradish peroxidase-testosterone conjugate for the enzyme-linked immunoassay of testosterone was investigated, using tritiated testosterone to follow the reaction. The formation of testosterone-3-(carboxymethyl) oxime-peroxidase by the mixed anhydride method was found to give a conjugate of high enzymatic activity and with three molecules of testosterone per molecule of peroxidase. The optimum conditions for the assay of peroxidase activity were studied and an assay capable of measuring 1 to 5 ng of the conjugate developed; the standard curve being virtually linear. The stability of the conjugate in solution and the effect of lyophilisation on enzymatic activity are also described. The peroxidase-testosterone conjugate was suitable for enzyme-linked immunoassay and the quantities measurable with the peroxidase assay covered the range necessary for a plasma testosterone assay. The stability of the conjugate was such that no particular precautions were necessary for its storage.", "contents": "The conjugation of testosterone with horseradish peroxidase and a sensitive enzyme assay for the conjugate. The formation of a horseradish peroxidase-testosterone conjugate for the enzyme-linked immunoassay of testosterone was investigated, using tritiated testosterone to follow the reaction. The formation of testosterone-3-(carboxymethyl) oxime-peroxidase by the mixed anhydride method was found to give a conjugate of high enzymatic activity and with three molecules of testosterone per molecule of peroxidase. The optimum conditions for the assay of peroxidase activity were studied and an assay capable of measuring 1 to 5 ng of the conjugate developed; the standard curve being virtually linear. The stability of the conjugate in solution and the effect of lyophilisation on enzymatic activity are also described. The peroxidase-testosterone conjugate was suitable for enzyme-linked immunoassay and the quantities measurable with the peroxidase assay covered the range necessary for a plasma testosterone assay. The stability of the conjugate was such that no particular precautions were necessary for its storage."}
{"id": "PMID:19861", "title": "[Quantitative determination of protector activity of fibrinogen tryptic hydrolysates].", "content": "A method is developed for the quantitative determination of the protector activity. The method is based on registrating the coagulation time shortening for a mixture of fibrin monomer and fragment D. All determinations should be carried out at high concentrations of fragment D when its inhibitory effect on fibrin polymerization is very strong. It is necessary to control the exact conditions as to ionic strength and pH of the reaction mixture. Another approach to the protector activity estimation is demonstrated. It is based on determination of clot protein quantities after fibrin monomer clotting in mixtures with constant fragment D and different protector quantities.", "contents": "[Quantitative determination of protector activity of fibrinogen tryptic hydrolysates]. A method is developed for the quantitative determination of the protector activity. The method is based on registrating the coagulation time shortening for a mixture of fibrin monomer and fragment D. All determinations should be carried out at high concentrations of fragment D when its inhibitory effect on fibrin polymerization is very strong. It is necessary to control the exact conditions as to ionic strength and pH of the reaction mixture. Another approach to the protector activity estimation is demonstrated. It is based on determination of clot protein quantities after fibrin monomer clotting in mixtures with constant fragment D and different protector quantities."}
{"id": "PMID:19862", "title": "[Effect of phosphoenolpyruvate on creatine kinase activity in rabbit muscles].", "content": "Phosphoenolpyruvate (PEP) is a potent inhibitor of muscle creatine kinase. The inhibition of ATP formation is more pronounced at pH 7.0. The substrates, creatine and creatine phosphate, partially prevent the inhibition of the enzyme activity by PEP, creatine being as an effector.", "contents": "[Effect of phosphoenolpyruvate on creatine kinase activity in rabbit muscles]. Phosphoenolpyruvate (PEP) is a potent inhibitor of muscle creatine kinase. The inhibition of ATP formation is more pronounced at pH 7.0. The substrates, creatine and creatine phosphate, partially prevent the inhibition of the enzyme activity by PEP, creatine being as an effector."}
{"id": "PMID:19863", "title": "[Transfer electron and hydrogen atom in model and enzymatic reactions of NAD and NADP].", "content": "The paper deals with the mechanism of some model reactions of NAD and NADP which proceed with transfer of one electron and hydrogen atom. The joint oxidation of N-benzyl-1,4-dihydronicotinamide (I) and phenylglyoxal with hydrogen peroxide in the presence of cupric ions is found to result in transfer of one hydrogen atom from dihydropyridine molecule to hydroxy-radical and the electron to a molecule of oxygen or dinitrobenzene. The oxydation of I with benzoquinone is found to proceed with formation of free radicals as intermediate. The mechanism of NAD reduction with sodium hydrosulphite is proposed.", "contents": "[Transfer electron and hydrogen atom in model and enzymatic reactions of NAD and NADP]. The paper deals with the mechanism of some model reactions of NAD and NADP which proceed with transfer of one electron and hydrogen atom. The joint oxidation of N-benzyl-1,4-dihydronicotinamide (I) and phenylglyoxal with hydrogen peroxide in the presence of cupric ions is found to result in transfer of one hydrogen atom from dihydropyridine molecule to hydroxy-radical and the electron to a molecule of oxygen or dinitrobenzene. The oxydation of I with benzoquinone is found to proceed with formation of free radicals as intermediate. The mechanism of NAD reduction with sodium hydrosulphite is proposed."}
{"id": "PMID:19864", "title": "[Changes in lipid and carbohydrate metabolism in rat tissues under combined effect of hypercapnia, hypoxia and cooling].", "content": "The cooling of rats under conditions of hypercapnia and hypoxia during the first 15 minutes increases the contents of free fatty acids, acetoacetate and beta-oxybutyrate in the tissues of the brain, myocardium, liver, skeletal muscles and blood and decreases them by the end of the effect (120 min later) down to the initial values, in the liver and skeletal muscles tissues the content of the mentioned intermediates falls lower the initial values. In the carbohydrate metabolism the amount of phosphoenolpyruvate 15 and 120 min after the action beginning and the amount of malate in the myocardium and brain at the end of the experiment increase to a different extent; the content of lactate rises only in the brain 30 and 120 min after the beginning of cooling. In the rat venous blood the value of pCO2 increases up to 71.8+/-6.0 mm Hg, the total content of CO2 rises, the values of the standard bicarbonates decrease and the pH value drops sharply down to 6.98+/-0.03. It is suggested that one of the main reasons of such changes in metabolism is development of hypercapnia state and acidosis and the resulted increase in intensity of the carboxylation processes in the tissues.", "contents": "[Changes in lipid and carbohydrate metabolism in rat tissues under combined effect of hypercapnia, hypoxia and cooling]. The cooling of rats under conditions of hypercapnia and hypoxia during the first 15 minutes increases the contents of free fatty acids, acetoacetate and beta-oxybutyrate in the tissues of the brain, myocardium, liver, skeletal muscles and blood and decreases them by the end of the effect (120 min later) down to the initial values, in the liver and skeletal muscles tissues the content of the mentioned intermediates falls lower the initial values. In the carbohydrate metabolism the amount of phosphoenolpyruvate 15 and 120 min after the action beginning and the amount of malate in the myocardium and brain at the end of the experiment increase to a different extent; the content of lactate rises only in the brain 30 and 120 min after the beginning of cooling. In the rat venous blood the value of pCO2 increases up to 71.8+/-6.0 mm Hg, the total content of CO2 rises, the values of the standard bicarbonates decrease and the pH value drops sharply down to 6.98+/-0.03. It is suggested that one of the main reasons of such changes in metabolism is development of hypercapnia state and acidosis and the resulted increase in intensity of the carboxylation processes in the tissues."}
{"id": "PMID:19865", "title": "[Peculiarities of aggregation in acid medium of immunoglobulin G peculiar to cancer].", "content": "Immunoglobulin G peculiar to cancer under the effect of acid medium changes to a slightly soluble form due to reversible formation of aggregates. The rest serum proteins transfer to the insoluble form in a more acid medium due to the irreversible denaturation changes in the protein molecules. When isolating aggregates of the mentioned protein from the blood serum of patients with cancer it is impossible to differ these sera from those of donors or patients with pathologies of nonmalignant character under the effect of acid medium. The amount of the aggregates isolated accounts for 1.1-1.2% of total amount of serum proteins and does not depend on affinity of the anion of acid in the presence of which the experiment was conducted for proteins.", "contents": "[Peculiarities of aggregation in acid medium of immunoglobulin G peculiar to cancer]. Immunoglobulin G peculiar to cancer under the effect of acid medium changes to a slightly soluble form due to reversible formation of aggregates. The rest serum proteins transfer to the insoluble form in a more acid medium due to the irreversible denaturation changes in the protein molecules. When isolating aggregates of the mentioned protein from the blood serum of patients with cancer it is impossible to differ these sera from those of donors or patients with pathologies of nonmalignant character under the effect of acid medium. The amount of the aggregates isolated accounts for 1.1-1.2% of total amount of serum proteins and does not depend on affinity of the anion of acid in the presence of which the experiment was conducted for proteins."}
{"id": "PMID:19866", "title": "[Structural changes in sarcolemma with E-avitaminosis dystrophy].", "content": "Sorption properties of sarcolemma preparations isolated from skeletal muscles of normal and E-avitaminous rabbits were studied relative to organic ions. Analysis of isotherms of sarcolemma equilibrium binding of neutral red cations and turquoise direct lightfast \"K\" anions made it possible to determine the number of positively and negetively charged sorption centres, which fix the mentioned dyes. With E-avitaminous muscular dystrophy the number of the centres increases considerably. A larger number of the positively charged centres fixing the surquoise dye are found both in the control and in case of dystrophy. The calcium ions prevent the neutral red sorption and intensify the turquoise direct sorption. In the sarcolemma preparations isolated from the muscles of the E-avitaminous rabbits the content of calcium ions is almost twice as high and the number of sulphydryl groups is 30-40% less as compare to the normal level. The data presented evidence for structural changes in sarcolemma with E-avitaminous muscular dystrophy.", "contents": "[Structural changes in sarcolemma with E-avitaminosis dystrophy]. Sorption properties of sarcolemma preparations isolated from skeletal muscles of normal and E-avitaminous rabbits were studied relative to organic ions. Analysis of isotherms of sarcolemma equilibrium binding of neutral red cations and turquoise direct lightfast \"K\" anions made it possible to determine the number of positively and negetively charged sorption centres, which fix the mentioned dyes. With E-avitaminous muscular dystrophy the number of the centres increases considerably. A larger number of the positively charged centres fixing the surquoise dye are found both in the control and in case of dystrophy. The calcium ions prevent the neutral red sorption and intensify the turquoise direct sorption. In the sarcolemma preparations isolated from the muscles of the E-avitaminous rabbits the content of calcium ions is almost twice as high and the number of sulphydryl groups is 30-40% less as compare to the normal level. The data presented evidence for structural changes in sarcolemma with E-avitaminous muscular dystrophy."}
{"id": "PMID:19872", "title": "[Pasteurella multocida bacteriophage adsorption].", "content": "Studied was the adsorption of 8 strains of Pasteurella multocida bacteriophages presenting three groups of phages isolated in Bulgaria. With the bacteriophages of groups I and II the adsorption in broth in the first 10 minutes amounted to 50-65%, and at the 80 the minute reached its maximum value--98-99%. With the bacteriophages of group III adsorption started with a lower percent and by the 140th minute reached 96-97%. It was by 60 min slower as compared with the adsorption with group I and II phages. In a veronal-medinal buffer the adsorption of all investigated phages of the three groups set in with a prolonged time of 60 min as compared with the time elapsed using broth. At the cross testing of adsorption the phages of group I were adsorbed by the hosts of the other two groups to a maximum level, however, the phages of groups II and III were adsorbed to a negligible extent on the other hosts (except for the adsorption on their homologous one). The difference established in the adsorption for a 60 minutes time so far as the phages of group III were concerned was sufficiently persuasive to consider this group as an individual one by this feature too. Adsorption appeared as a subsidiary taxonomic characteristic in the classification of Pasteurella multocida bacteriophages.", "contents": "[Pasteurella multocida bacteriophage adsorption]. Studied was the adsorption of 8 strains of Pasteurella multocida bacteriophages presenting three groups of phages isolated in Bulgaria. With the bacteriophages of groups I and II the adsorption in broth in the first 10 minutes amounted to 50-65%, and at the 80 the minute reached its maximum value--98-99%. With the bacteriophages of group III adsorption started with a lower percent and by the 140th minute reached 96-97%. It was by 60 min slower as compared with the adsorption with group I and II phages. In a veronal-medinal buffer the adsorption of all investigated phages of the three groups set in with a prolonged time of 60 min as compared with the time elapsed using broth. At the cross testing of adsorption the phages of group I were adsorbed by the hosts of the other two groups to a maximum level, however, the phages of groups II and III were adsorbed to a negligible extent on the other hosts (except for the adsorption on their homologous one). The difference established in the adsorption for a 60 minutes time so far as the phages of group III were concerned was sufficiently persuasive to consider this group as an individual one by this feature too. Adsorption appeared as a subsidiary taxonomic characteristic in the classification of Pasteurella multocida bacteriophages."}
{"id": "PMID:19879", "title": "The effect of dehydroemetine on vascular tissue.", "content": "The effect of dehydroemetine on vascular tissues was studied, using the aortic strip of the rabbit, the isolated perfused central ear artery of the rabbit and the perfused hind limb of the cat. Doses from 10(-6) to 10(-5) M inhibited the response of the aortic strip and the perfused ear artery to transmural electrical stimulation. 10(-5) M dehydroemetine completely blocked the response of the aortic strip to transmural stimulation. This dose however, had no significant effect on the response to exogenous noradrenaline and dexamphetamine. Doses ranging from 0.1-3 mg/kg caused transient falls in the perfusion pressure of the cat's hind limb. This fall was not blocked by propranolol, mepyramine nor atropine. It was concluded that the effect of dehydroemetine on vascular tissues was non-specific.", "contents": "The effect of dehydroemetine on vascular tissue. The effect of dehydroemetine on vascular tissues was studied, using the aortic strip of the rabbit, the isolated perfused central ear artery of the rabbit and the perfused hind limb of the cat. Doses from 10(-6) to 10(-5) M inhibited the response of the aortic strip and the perfused ear artery to transmural electrical stimulation. 10(-5) M dehydroemetine completely blocked the response of the aortic strip to transmural stimulation. This dose however, had no significant effect on the response to exogenous noradrenaline and dexamphetamine. Doses ranging from 0.1-3 mg/kg caused transient falls in the perfusion pressure of the cat's hind limb. This fall was not blocked by propranolol, mepyramine nor atropine. It was concluded that the effect of dehydroemetine on vascular tissues was non-specific."}
{"id": "PMID:19884", "title": "The metabolism of niclosamide and related compounds by Moniezia expansa, Ascaris lumbricoides var suum, and mouse- and sheep-liver enzymes.", "content": "1. Niclosamide and related nitro compounds were reduced to the corresponding amines by Moniezia expansa, Ascaris lumbricoides var suum and by enzymes prepared from these species and by mouse and sheep liver homogenates. The reduction of niclosamide by the helminths required as cofactors NADH2 and glutathione, but was inhibited 50% by 2 X 10(-7) M allopurinol. 2. Unlike benzanilide, niclosamide was not hydrolysed by either the helminths, or the mammalian liver preparations. Rates of hydrolysis of compounds related to niclosamide indicate that niclosamide was not hydrolysed because substituents in both benzene rings ortho to the amide bond sterically hinder the hydrolase. 3. Hydrolysis of benzanilide and related compounds was inhibited by anthelmintic organophosphates.", "contents": "The metabolism of niclosamide and related compounds by Moniezia expansa, Ascaris lumbricoides var suum, and mouse- and sheep-liver enzymes. 1. Niclosamide and related nitro compounds were reduced to the corresponding amines by Moniezia expansa, Ascaris lumbricoides var suum and by enzymes prepared from these species and by mouse and sheep liver homogenates. The reduction of niclosamide by the helminths required as cofactors NADH2 and glutathione, but was inhibited 50% by 2 X 10(-7) M allopurinol. 2. Unlike benzanilide, niclosamide was not hydrolysed by either the helminths, or the mammalian liver preparations. Rates of hydrolysis of compounds related to niclosamide indicate that niclosamide was not hydrolysed because substituents in both benzene rings ortho to the amide bond sterically hinder the hydrolase. 3. Hydrolysis of benzanilide and related compounds was inhibited by anthelmintic organophosphates."}
{"id": "PMID:19885", "title": "The metabolism of the neuroleptic agent 1 (4'-fluorophenyl)-4-(cyclohexyl-1'-piperzinyl-4'-carboxylated)-butan-1-one hydrochloride in rats and man.", "content": "1. An oral dose the neuroleptic agent 1-(4'-fluorophenyl)-4-(cyclohexyl-1'-(14C)piperazinyl-4'-carboxylate)butan-1-one was mainly eliminated in the urine within 12 h by rats and man. During 5 days, 63-6% and 83-3% was eliminated in the urine of rats and man respectively. 2. Plasma concentrations in man related a maximum during 30 min to 1 h, representing 1-43 microgram equiv./ml. The proportion of unchanged drug in plasma decreased from 48% at 15 min to less than 10% after 1 h. 3. Seven major radioactive components were detected in the chloroform extract of basified rat urine and five major components in similar extracts of human urine. The major rat metabolites were isolated and identified by mass spectrometry as components resulting from mono- and dihydroxylation in the cyclohexane ring, reduction of the keto group to a secondary alcohol and hydrolysis and decarboxylation of the cyclohexylcarbamoyl group. The major metabolite in the rat urine extract was the dihydroxylated secondary alcohol derivative while the major human metabolite was the monohydroxylated secondary alcohol derivative. The metabolites were also partly eliminated as conjugates.", "contents": "The metabolism of the neuroleptic agent 1 (4'-fluorophenyl)-4-(cyclohexyl-1'-piperzinyl-4'-carboxylated)-butan-1-one hydrochloride in rats and man. 1. An oral dose the neuroleptic agent 1-(4'-fluorophenyl)-4-(cyclohexyl-1'-(14C)piperazinyl-4'-carboxylate)butan-1-one was mainly eliminated in the urine within 12 h by rats and man. During 5 days, 63-6% and 83-3% was eliminated in the urine of rats and man respectively. 2. Plasma concentrations in man related a maximum during 30 min to 1 h, representing 1-43 microgram equiv./ml. The proportion of unchanged drug in plasma decreased from 48% at 15 min to less than 10% after 1 h. 3. Seven major radioactive components were detected in the chloroform extract of basified rat urine and five major components in similar extracts of human urine. The major rat metabolites were isolated and identified by mass spectrometry as components resulting from mono- and dihydroxylation in the cyclohexane ring, reduction of the keto group to a secondary alcohol and hydrolysis and decarboxylation of the cyclohexylcarbamoyl group. The major metabolite in the rat urine extract was the dihydroxylated secondary alcohol derivative while the major human metabolite was the monohydroxylated secondary alcohol derivative. The metabolites were also partly eliminated as conjugates."}
{"id": "PMID:19886", "title": "[Thermal inactivation and storage behavior of technologically important enzymes. IV. Spinach lipid-acyl-hydrolase].", "content": "The thermal reaction of a lipid-acyl-hydrolase which seems to be important for the quality preservation of vegetable foods, was investigated in spinach. The authors applied a simple in-situ method using thin-layer chromatography which had been developed for the enzyme determination, to follow the thermal inactivation of the lipid-acyl-hydrolase by measuring the decomposition of lecithin, mono- und digalactosyl diglycerides. According to the inactivation curves, the enzyme is relatively little resistant to heat. Since the D- and z-values resulting from the inactivation curves for phospholipase, mono- and digalacto-lipase activities are almost the same, it can be assumed that the lipid-acyl-hydrolase is a multi-function enzyme in spinach.", "contents": "[Thermal inactivation and storage behavior of technologically important enzymes. IV. Spinach lipid-acyl-hydrolase]. The thermal reaction of a lipid-acyl-hydrolase which seems to be important for the quality preservation of vegetable foods, was investigated in spinach. The authors applied a simple in-situ method using thin-layer chromatography which had been developed for the enzyme determination, to follow the thermal inactivation of the lipid-acyl-hydrolase by measuring the decomposition of lecithin, mono- und digalactosyl diglycerides. According to the inactivation curves, the enzyme is relatively little resistant to heat. Since the D- and z-values resulting from the inactivation curves for phospholipase, mono- and digalacto-lipase activities are almost the same, it can be assumed that the lipid-acyl-hydrolase is a multi-function enzyme in spinach."}
{"id": "PMID:19887", "title": "[Thermal inactivation and storage behavior of technologically important enzymes. I. Horseradish and spinach peroxidase].", "content": "The thermal inactivation and storage behaviour for horseradish and spinach peroxidases were investigated in defined systems, in spinach also within its natural environment. The inactivation curves of either enzyme show a sharp bend which is clearly visible at low, but not at higher temperatures. The D-values were taken from the inactivation curves. z-values resulting from the D-values were 25.5 degrees C for horseradish peroxidase, 13 degrees C for isolated peroxidase and 18 degrees C for peroxidase in spinach extract. Horseradish peroxidase was relatively heat-resistent at pH 6.0, spinach peroxidase at pH 5.0-6.0; both enzymes were found to be highly susceptible to heat at pH 4.0. Peroxidase isolated from spinach responded differently to heating than the enzyme in spinach extract or suspension. This discrepancy indicates that certain model experiments cannot be transferred to foods. Heated peroxidase from horseradish and spinach were found to regenerate during storage; the extent of regeneration depended on the pH.", "contents": "[Thermal inactivation and storage behavior of technologically important enzymes. I. Horseradish and spinach peroxidase]. The thermal inactivation and storage behaviour for horseradish and spinach peroxidases were investigated in defined systems, in spinach also within its natural environment. The inactivation curves of either enzyme show a sharp bend which is clearly visible at low, but not at higher temperatures. The D-values were taken from the inactivation curves. z-values resulting from the D-values were 25.5 degrees C for horseradish peroxidase, 13 degrees C for isolated peroxidase and 18 degrees C for peroxidase in spinach extract. Horseradish peroxidase was relatively heat-resistent at pH 6.0, spinach peroxidase at pH 5.0-6.0; both enzymes were found to be highly susceptible to heat at pH 4.0. Peroxidase isolated from spinach responded differently to heating than the enzyme in spinach extract or suspension. This discrepancy indicates that certain model experiments cannot be transferred to foods. Heated peroxidase from horseradish and spinach were found to regenerate during storage; the extent of regeneration depended on the pH."}
{"id": "PMID:19888", "title": "[Effects of a coffee-antacid-mixture and a commercial coffee with regard to gastrin, pH and gastric secretion (author's transl)].", "content": "The influence of a coffee-antazid-mixture was investigated at 30 patients with diseases of the stomach (17 with duodenal ulcer, 6 with gastric ulcer and 7 with chronic gastritis) in comparison to a commercial coffee. The parameters measured were the gastric basal acid output, the continuous registration of the pH by an intragastric electrode and the serum gastrin concentration before and after the application of the tests substances. 75% of the patients with duodenal ulcer showed a positive effect by means of a greater elevation of the intragastric pH after application of the mixture in comparison to coffee. The effect was strongly correlated to the basal acid ouptput. In the group with gastric ulcer and that with duodenal ulcer under the influence of the mixture the pH after the initial rise decreased to less deeper values. There was a close relationship to the patterns of gastric ulcer as well with chronic gastritis there was an additional facourable effect on the symptoms of abdominal pain which occured after coffee and not after the mixture. The group with chronic gastritis showed no difference between the pure coffee and the coffee-antacid-mixture. A possible relationship of the products of coffee roasting and the adsorptive properties of the antacid is discussed.", "contents": "[Effects of a coffee-antacid-mixture and a commercial coffee with regard to gastrin, pH and gastric secretion (author's transl)]. The influence of a coffee-antazid-mixture was investigated at 30 patients with diseases of the stomach (17 with duodenal ulcer, 6 with gastric ulcer and 7 with chronic gastritis) in comparison to a commercial coffee. The parameters measured were the gastric basal acid output, the continuous registration of the pH by an intragastric electrode and the serum gastrin concentration before and after the application of the tests substances. 75% of the patients with duodenal ulcer showed a positive effect by means of a greater elevation of the intragastric pH after application of the mixture in comparison to coffee. The effect was strongly correlated to the basal acid ouptput. In the group with gastric ulcer and that with duodenal ulcer under the influence of the mixture the pH after the initial rise decreased to less deeper values. There was a close relationship to the patterns of gastric ulcer as well with chronic gastritis there was an additional facourable effect on the symptoms of abdominal pain which occured after coffee and not after the mixture. The group with chronic gastritis showed no difference between the pure coffee and the coffee-antacid-mixture. A possible relationship of the products of coffee roasting and the adsorptive properties of the antacid is discussed."}
{"id": "PMID:19901", "title": "[Experiences on the effectivity of prostaglandin F2alpha during labor after insufficient effect of oxytocin].", "content": "A report is given about the efficacy of prostaglandin F2alpha for induction of labour after inefficient application of oxytocininfusion. In all cases induction of labour was indicated or labour should be supported. 80 of the 104 women with weak labour finally delivered on vaginal way. Only 9 of 24 caesarean sections were performed by reason of weak labour in spite of application of prostaglandin F2alpha. There was no influence on the state of the newborns, this was the result of postnatal judgment by Apgar-score.", "contents": "[Experiences on the effectivity of prostaglandin F2alpha during labor after insufficient effect of oxytocin]. A report is given about the efficacy of prostaglandin F2alpha for induction of labour after inefficient application of oxytocininfusion. In all cases induction of labour was indicated or labour should be supported. 80 of the 104 women with weak labour finally delivered on vaginal way. Only 9 of 24 caesarean sections were performed by reason of weak labour in spite of application of prostaglandin F2alpha. There was no influence on the state of the newborns, this was the result of postnatal judgment by Apgar-score."}
{"id": "PMID:19903", "title": "[Morphofunctional changes in the thymus of semisyngenous chimeras during the \"graft versus host\" response].", "content": "Activation of the enzymatic processes in the thymus cells was noted in the thymus gland at the early stages of the \"transplantat-versus-host\" reaction; the later stages were attended by inhibition of metabolic processes and reduction in number of immature and mature thymocytes in the cortical substance of the thymus. Besides, the cortical substance displayed accumulation of mesenchymal macrophages rich in lysosomal enzymes, particularly in the subcapsular layer where small foci of destruction formed at the late stages of the reaction.", "contents": "[Morphofunctional changes in the thymus of semisyngenous chimeras during the \"graft versus host\" response]. Activation of the enzymatic processes in the thymus cells was noted in the thymus gland at the early stages of the \"transplantat-versus-host\" reaction; the later stages were attended by inhibition of metabolic processes and reduction in number of immature and mature thymocytes in the cortical substance of the thymus. Besides, the cortical substance displayed accumulation of mesenchymal macrophages rich in lysosomal enzymes, particularly in the subcapsular layer where small foci of destruction formed at the late stages of the reaction."}
{"id": "PMID:19905", "title": "[Dynamic study of blood cholinesterase activity of paranoid schizophrenic patients].", "content": "A comparison of the cholinesterase blood activity with the clinical traits of the disease in 64 patients with paranoid schizophrenia treated by majeptile and haloperidol detected 2 variants in the reactivity of the enzyme link of the cholinergic system. A fluctuation of the cholinesterase activity of the sinusoid type (Ist variant) seen in patients with paranoial and hallucinatory-paranoid syndromes with a remission up to a year and more, speaks in favour of a relatively preserved compensatory-adaptive mechanisms in the neurohumoral regulation. The absence of fluctuation in the cholinesterase activity during the whole period of treatment (2nd variant) was characteristic of patients with negative results of treatment.", "contents": "[Dynamic study of blood cholinesterase activity of paranoid schizophrenic patients]. A comparison of the cholinesterase blood activity with the clinical traits of the disease in 64 patients with paranoid schizophrenia treated by majeptile and haloperidol detected 2 variants in the reactivity of the enzyme link of the cholinergic system. A fluctuation of the cholinesterase activity of the sinusoid type (Ist variant) seen in patients with paranoial and hallucinatory-paranoid syndromes with a remission up to a year and more, speaks in favour of a relatively preserved compensatory-adaptive mechanisms in the neurohumoral regulation. The absence of fluctuation in the cholinesterase activity during the whole period of treatment (2nd variant) was characteristic of patients with negative results of treatment."}
{"id": "PMID:19906", "title": "[Sex gland morphology of schizophrenic patients during treatment with psychotropic drugs].", "content": "A macro- and microscopic study of genital glands was conducted in 33 cases of schizophrenia (14 females and 19 males). A practically normal histological picture of the ovary and testis was found in 12 cases, different degrees of involutional (atrophic) changes in 19 and tumours in 2 cases. The degree of expressed histological changes correlated with age and duration of the disease. Correlation between the histology of genital glands on the one hand and the duration and intensity of psychopharmacological treatment on the other one (mainly by neuroleptics) were not found.", "contents": "[Sex gland morphology of schizophrenic patients during treatment with psychotropic drugs]. A macro- and microscopic study of genital glands was conducted in 33 cases of schizophrenia (14 females and 19 males). A practically normal histological picture of the ovary and testis was found in 12 cases, different degrees of involutional (atrophic) changes in 19 and tumours in 2 cases. The degree of expressed histological changes correlated with age and duration of the disease. Correlation between the histology of genital glands on the one hand and the duration and intensity of psychopharmacological treatment on the other one (mainly by neuroleptics) were not found."}
{"id": "PMID:19907", "title": "[Several indices of the methylation process in schizophrenic patients].", "content": "The paper deals with a study of 83 patients with different forms of schizophrenia and 15 normals where the methylating activity in converting nicotinamid into methylnicotinamid was determined and the activity of catechol-methyltransferase. In schizophrenic patients there is an increase of the methylating activity which significantly correlated with hallucinatory symptoms in the clinical picture. In patients with cataono-paranoid, paranoid syndromes and simple forms of schizophrenia the methylating activity is seen significantly less frequently. The disappearance of alleviation of hallucinations, due to neuroleptical drugs is accompanied by normalization of the methylating activity. Any significant differences in the excretion of isdarin as an index of cathechol-o-methyltransferase activity in normals and schizophrenic patients was not established.", "contents": "[Several indices of the methylation process in schizophrenic patients]. The paper deals with a study of 83 patients with different forms of schizophrenia and 15 normals where the methylating activity in converting nicotinamid into methylnicotinamid was determined and the activity of catechol-methyltransferase. In schizophrenic patients there is an increase of the methylating activity which significantly correlated with hallucinatory symptoms in the clinical picture. In patients with cataono-paranoid, paranoid syndromes and simple forms of schizophrenia the methylating activity is seen significantly less frequently. The disappearance of alleviation of hallucinations, due to neuroleptical drugs is accompanied by normalization of the methylating activity. Any significant differences in the excretion of isdarin as an index of cathechol-o-methyltransferase activity in normals and schizophrenic patients was not established."}
{"id": "PMID:19909", "title": "The stenosis of the terminal esophagus after surgical repair of the hiatus hernia.", "content": "Eighty-two operations of hiatus hernia repair were performed at the General Surgery Department of the University of Padua from 1966 to 1975. Two cases of iatrogenic stenosis of the the terminal esophagus, whose correction required postoperative dilatations, occurred in this series. This complication should be separated from the transient dysphagia frequent occurring, without radiologia or endoscopic evidence of esophageal lesions, after hiatus hernia repair. The stenosis followed two different repair techniques but, at present time, it is impossible to establish a relationship between occurrence of the iatrogenic lesion and repair techniques used. Eventhough iatrogenic stenosis of the terminal esophagus does not occur frequently, it is a possible complication to keep in mind while performing hiatus hernia repair, because it is exclusively related to defects of the surgical technique.", "contents": "The stenosis of the terminal esophagus after surgical repair of the hiatus hernia. Eighty-two operations of hiatus hernia repair were performed at the General Surgery Department of the University of Padua from 1966 to 1975. Two cases of iatrogenic stenosis of the the terminal esophagus, whose correction required postoperative dilatations, occurred in this series. This complication should be separated from the transient dysphagia frequent occurring, without radiologia or endoscopic evidence of esophageal lesions, after hiatus hernia repair. The stenosis followed two different repair techniques but, at present time, it is impossible to establish a relationship between occurrence of the iatrogenic lesion and repair techniques used. Eventhough iatrogenic stenosis of the terminal esophagus does not occur frequently, it is a possible complication to keep in mind while performing hiatus hernia repair, because it is exclusively related to defects of the surgical technique."}
{"id": "PMID:19917", "title": "Saliva tests in the prognosis of caries in children.", "content": "The purpose of the investigation was to find out whether the negative correlations between caries indices and the flow rate, pH and buffer effect of saliva that could be demonstrated in groups of 8- and 5-year-old children, were close enough to allow prediction of the development of caries in a given child. The results showed that the range of variation of the results of all analyses were very wide. This makes the use of saliva tests alone in the prognosis of caries development of less value in the individual child.", "contents": "Saliva tests in the prognosis of caries in children. The purpose of the investigation was to find out whether the negative correlations between caries indices and the flow rate, pH and buffer effect of saliva that could be demonstrated in groups of 8- and 5-year-old children, were close enough to allow prediction of the development of caries in a given child. The results showed that the range of variation of the results of all analyses were very wide. This makes the use of saliva tests alone in the prognosis of caries development of less value in the individual child."}
{"id": "PMID:19918", "title": "Ocular encephalitozoonosis (nosematosis) in blue foxes. Polyarteritis nodosa and cataract.", "content": "In young blue foxes an association has previously been established between the protozoon Encephalitozoon (Nosema) cuniculi and generalized arterial lesions of the polyarteritis nodosa type. The same vascular changes are found in the posterior ciliary arteries and their intraocular branches of these foxes. Most of the eyes which are thus affected, have a severe cataract. The parasite can easily be demonstrated both in the arteries and the lenses. It is thought that the Encephalitozoon is the cause of the vascular lesions and the cataract, and that possibly an autoimmune reaction is involved.", "contents": "Ocular encephalitozoonosis (nosematosis) in blue foxes. Polyarteritis nodosa and cataract. In young blue foxes an association has previously been established between the protozoon Encephalitozoon (Nosema) cuniculi and generalized arterial lesions of the polyarteritis nodosa type. The same vascular changes are found in the posterior ciliary arteries and their intraocular branches of these foxes. Most of the eyes which are thus affected, have a severe cataract. The parasite can easily be demonstrated both in the arteries and the lenses. It is thought that the Encephalitozoon is the cause of the vascular lesions and the cataract, and that possibly an autoimmune reaction is involved."}
{"id": "PMID:19920", "title": "Role of feeding on lipase activity in gastric contents.", "content": "Lipase activity was recorded in gastric contents collected from healthy term and preterm neonates. In contrast to pancreatic lipase activity this lipase activity was higher at pH 5.5 than at pH 8.0 and it was more resistent to acid inactivation. Lipase activity was found in gastric contents from all infants who were regularly fed, but was not present in gastric contents from some infants when collected before regular feeding was established. During test meals lipase activity in gastric contents increased considerably in all infants studied. During such a test meal there was a progressive relative decrease in triglycerides whilst diglycerides showed a relative increase suggesting an active lipolytic process in the stomach. An assay procedure for determination of lipase activity in gastric contents is also described.", "contents": "Role of feeding on lipase activity in gastric contents. Lipase activity was recorded in gastric contents collected from healthy term and preterm neonates. In contrast to pancreatic lipase activity this lipase activity was higher at pH 5.5 than at pH 8.0 and it was more resistent to acid inactivation. Lipase activity was found in gastric contents from all infants who were regularly fed, but was not present in gastric contents from some infants when collected before regular feeding was established. During test meals lipase activity in gastric contents increased considerably in all infants studied. During such a test meal there was a progressive relative decrease in triglycerides whilst diglycerides showed a relative increase suggesting an active lipolytic process in the stomach. An assay procedure for determination of lipase activity in gastric contents is also described."}
{"id": "PMID:19921", "title": "Prevention of kernicterus, based on recent progress in bilirubin chemistry.", "content": "A review is presented of recent progress in bilirubin chemistry, its binding to albumin, displacement by drugs, and the mechanism of phototherapy. Quantitative formulations of the effect of albumin dosage, of varying pH, and of fatty acids result in a diagram which may be tried as an aid to indications for therapy.", "contents": "Prevention of kernicterus, based on recent progress in bilirubin chemistry. A review is presented of recent progress in bilirubin chemistry, its binding to albumin, displacement by drugs, and the mechanism of phototherapy. Quantitative formulations of the effect of albumin dosage, of varying pH, and of fatty acids result in a diagram which may be tried as an aid to indications for therapy."}
{"id": "PMID:19922", "title": "Chemical composition, serological reactivity and endotoxicity of lipopolysaccharides extracted in different ways from Bacteroides fragilis, Bacteroides melaninogenicus and Bacteroides oralis.", "content": "Lipopolysaccharides (LPS) extracted from strains of Bacteroides fragilis, Bacteroides melaninogenicus and Bacteroides oralis with phenol-water, trichloroacetic acid, EDTA or liquid phenol-chloroform-petroleum ether (PCP) and isolated by ultracentrifugation, varied considerably in their quantitative chemical composition. Negligible yields of LPS were obtained by PCP-extraction. All preparations were more or less serologically active. All methods (except PCP) extracted the same O-antigenic determinants from B. fragilis. Endotoxic activity, as measured by primary skin inflammations in rabbits, was low but was present in all preparations. Proteins (and/or lipoproteins) co-precipitated with LPS in the ultracentrifuge.", "contents": "Chemical composition, serological reactivity and endotoxicity of lipopolysaccharides extracted in different ways from Bacteroides fragilis, Bacteroides melaninogenicus and Bacteroides oralis. Lipopolysaccharides (LPS) extracted from strains of Bacteroides fragilis, Bacteroides melaninogenicus and Bacteroides oralis with phenol-water, trichloroacetic acid, EDTA or liquid phenol-chloroform-petroleum ether (PCP) and isolated by ultracentrifugation, varied considerably in their quantitative chemical composition. Negligible yields of LPS were obtained by PCP-extraction. All preparations were more or less serologically active. All methods (except PCP) extracted the same O-antigenic determinants from B. fragilis. Endotoxic activity, as measured by primary skin inflammations in rabbits, was low but was present in all preparations. Proteins (and/or lipoproteins) co-precipitated with LPS in the ultracentrifuge."}
{"id": "PMID:19919", "title": "Purulent and non-purulent maxillary sinus secretions with respect to pO2, pCO2 and pH.", "content": "Antral secretions from patients with maxillary sinusitis were aspirated for determination of pO2, pCO2 and pH. In 14 non-purulent secretions the mean pO2 was 12.7 kPa (96 mmHg) and the mean pCO2 5.2 kPa (39 mmHg). The mean pH was slightly alkaline. In 18 purulent secretions, usually with a heavy growth of pneumococci or H. influenzae, the pO2 was zero or close to zero and the mean pCO2 greater than or equal to 10.1 kPa (greater than or equal to 76 mmHg). The mean pH was slightly acid and significantly lower than in the nonpurulent secretions. The gas composition and the pH in purulent secretions do not only influence the metabolic activity and multiplication of bacteria, but may also interfere with the local protective functions of the sinus mucosa and with the bactericidal function of granulocytes.", "contents": "Purulent and non-purulent maxillary sinus secretions with respect to pO2, pCO2 and pH. Antral secretions from patients with maxillary sinusitis were aspirated for determination of pO2, pCO2 and pH. In 14 non-purulent secretions the mean pO2 was 12.7 kPa (96 mmHg) and the mean pCO2 5.2 kPa (39 mmHg). The mean pH was slightly alkaline. In 18 purulent secretions, usually with a heavy growth of pneumococci or H. influenzae, the pO2 was zero or close to zero and the mean pCO2 greater than or equal to 10.1 kPa (greater than or equal to 76 mmHg). The mean pH was slightly acid and significantly lower than in the nonpurulent secretions. The gas composition and the pH in purulent secretions do not only influence the metabolic activity and multiplication of bacteria, but may also interfere with the local protective functions of the sinus mucosa and with the bactericidal function of granulocytes."}
{"id": "PMID:19927", "title": "Studies on fish liver protein synthesis. II. Factors influencing the aminoacylation of shark liver transfer ribonucleic acid.", "content": "The influence of buffer, pH, Mg2+, ATP, Na+, K+ and temperature on the extent and rate of aminoacyl-tRNA synthesis was studied with the shark Mustelus mento liver tRNAs and aminoacyl-tRNA synthetases. The optimum pH for the aminoacylation of tRNAMet was 8.3 and for tRNAVal 7.0. For these two tRNAs the Mg2+ optimum was related to the levels of ATP required and to the pH of the reactions. It is suggested that the Mg2+ concentration required for each aminoacylation system reflects the true conditions under which the substrate for the enzyme, the MgATP2- complex, is formed. The effect of monovalent cations was also examined. Val-tRNA synthesis was slightly stimulated up to a concentration of 50 mM NaCl (KCl). Over 100 mM salt, a rapid inhibition was observed. Met-tRNA synthesis behaves differently by being stimulated over a wide range of salt concentrations.", "contents": "Studies on fish liver protein synthesis. II. Factors influencing the aminoacylation of shark liver transfer ribonucleic acid. The influence of buffer, pH, Mg2+, ATP, Na+, K+ and temperature on the extent and rate of aminoacyl-tRNA synthesis was studied with the shark Mustelus mento liver tRNAs and aminoacyl-tRNA synthetases. The optimum pH for the aminoacylation of tRNAMet was 8.3 and for tRNAVal 7.0. For these two tRNAs the Mg2+ optimum was related to the levels of ATP required and to the pH of the reactions. It is suggested that the Mg2+ concentration required for each aminoacylation system reflects the true conditions under which the substrate for the enzyme, the MgATP2- complex, is formed. The effect of monovalent cations was also examined. Val-tRNA synthesis was slightly stimulated up to a concentration of 50 mM NaCl (KCl). Over 100 mM salt, a rapid inhibition was observed. Met-tRNA synthesis behaves differently by being stimulated over a wide range of salt concentrations."}
{"id": "PMID:19928", "title": "Purchases of hypnotics, sedatives and minor tranquillizers among 2,566 individuals in the county of J\u00e4mtland, Sweden. A 6-year follow-up.", "content": "Data from a continuous recording of drug prescriptions to 16,600 individuals in the county of J\u00e4mtland, Sweden, revealed that 2,566 patients (15.5%) obtained prescriptions for hypnotics, sedatives and minor tranquillizers in 1970. Occasional use (one purchase only, Group A) was seen in 7.4% of the population, intermediate use (two to six purchases, Group B) in 6.9% whereas 1.2% were regular users (seven purchases or more, Group C). For each group as a whole there was 5 years later a highly significant intraindividual reduction in the purchases of these drugs as well as of other psychotropic drugs. In all groups 10-23% had increased their purchases, most of them insignificantly. Fifteen of 30 patients with a marked increase in consumption developed a regular purchase pattern, but signs of overuse or abuse were seen in only four persons. During the studied period the benzodiazepines increased their share of the total from 45 to 60%. Antihistamines also increased in all groups while the proportion of barbiturates and combined preparations decreased markedly.", "contents": "Purchases of hypnotics, sedatives and minor tranquillizers among 2,566 individuals in the county of J\u00e4mtland, Sweden. A 6-year follow-up. Data from a continuous recording of drug prescriptions to 16,600 individuals in the county of J\u00e4mtland, Sweden, revealed that 2,566 patients (15.5%) obtained prescriptions for hypnotics, sedatives and minor tranquillizers in 1970. Occasional use (one purchase only, Group A) was seen in 7.4% of the population, intermediate use (two to six purchases, Group B) in 6.9% whereas 1.2% were regular users (seven purchases or more, Group C). For each group as a whole there was 5 years later a highly significant intraindividual reduction in the purchases of these drugs as well as of other psychotropic drugs. In all groups 10-23% had increased their purchases, most of them insignificantly. Fifteen of 30 patients with a marked increase in consumption developed a regular purchase pattern, but signs of overuse or abuse were seen in only four persons. During the studied period the benzodiazepines increased their share of the total from 45 to 60%. Antihistamines also increased in all groups while the proportion of barbiturates and combined preparations decreased markedly."}
{"id": "PMID:19929", "title": "Peripheral haemodynamics in essential hypertension.", "content": "Previous studies have indicated the existance of haemodynamically important structural vascular changes in patients and animals with hypertension. Possible pathophysiological implications of these changes are discussed. Two studies dealing with the question of reversibility of the structural changes on long-term blood pressure lowering therapy are described. The results indicate that the changes are partially but not completely reversible.", "contents": "Peripheral haemodynamics in essential hypertension. Previous studies have indicated the existance of haemodynamically important structural vascular changes in patients and animals with hypertension. Possible pathophysiological implications of these changes are discussed. Two studies dealing with the question of reversibility of the structural changes on long-term blood pressure lowering therapy are described. The results indicate that the changes are partially but not completely reversible."}
{"id": "PMID:19937", "title": "The oxygen sensing characteristics of microsomal enzymes.", "content": "The microsomal electron transport complex, in particular the segment associated with cytochrome P-450 function, is both qualitatively and quantitatively an important contributor to the cellular respiration of tissues such as liver. Although our knowledge is still limited, it is apparent that oxygen plays a pivitol role in dictating the mode of substrate hydroxylation or the generation of hydrogen peroxide. As illustrated in Figure 7, current evidence suggests that hydrogen peroxide is formed by the dismutation of the superoxide anion resulting from the dissociation of oxycytochrome P-450. Of interest are recent studies demonstrating the ability of hydrogen peroxide to initiate a cytochrome P-450 dependent peroxidatic reaction competent for supporting substrate hydroxylation. The fact that the function of cytochrome P-450 is sensitive to changes in oxygen tension establishes its role as an \"oxygen sensor\" for cellular metabolism.", "contents": "The oxygen sensing characteristics of microsomal enzymes. The microsomal electron transport complex, in particular the segment associated with cytochrome P-450 function, is both qualitatively and quantitatively an important contributor to the cellular respiration of tissues such as liver. Although our knowledge is still limited, it is apparent that oxygen plays a pivitol role in dictating the mode of substrate hydroxylation or the generation of hydrogen peroxide. As illustrated in Figure 7, current evidence suggests that hydrogen peroxide is formed by the dismutation of the superoxide anion resulting from the dissociation of oxycytochrome P-450. Of interest are recent studies demonstrating the ability of hydrogen peroxide to initiate a cytochrome P-450 dependent peroxidatic reaction competent for supporting substrate hydroxylation. The fact that the function of cytochrome P-450 is sensitive to changes in oxygen tension establishes its role as an \"oxygen sensor\" for cellular metabolism."}
{"id": "PMID:19945", "title": "Evaluation of research on control of prolactin secretion.", "content": "At least three substances have been reported to be present in the hypothalamus that can inhibit prolactin release, namely a PIF, catecholamines and acetylcholine. At least four substances have been reported to be present in the hypothalamus that can stimulate prolactin release, namely PRF, TRH, serotonin and prostaglandins. Neither the existence of a distinctive PIF or PRF in the hypothalamus can be considered as definitely established. The predominant action of the mammalian hypothalamus on prolactin release is inhibitory under most conditions, and is stimulatory in avian species. In addition to control by the hypothalamus, several hormones and drugs can act directly on the pituitary to alter prolactin release. The interrelationships of these agents within and without the hypothalamus on prolactin secretion are complex, and there are many questions about their mode of action. Studies on the regulation of prolactin secretion have resulted in development of many methods for either increasing or decreasing release of this important hormone, and thereby have provided opportunities for influencing lactation, growth of mammary and pituitary tumors and other tissues responsive to prolactin.", "contents": "Evaluation of research on control of prolactin secretion. At least three substances have been reported to be present in the hypothalamus that can inhibit prolactin release, namely a PIF, catecholamines and acetylcholine. At least four substances have been reported to be present in the hypothalamus that can stimulate prolactin release, namely PRF, TRH, serotonin and prostaglandins. Neither the existence of a distinctive PIF or PRF in the hypothalamus can be considered as definitely established. The predominant action of the mammalian hypothalamus on prolactin release is inhibitory under most conditions, and is stimulatory in avian species. In addition to control by the hypothalamus, several hormones and drugs can act directly on the pituitary to alter prolactin release. The interrelationships of these agents within and without the hypothalamus on prolactin secretion are complex, and there are many questions about their mode of action. Studies on the regulation of prolactin secretion have resulted in development of many methods for either increasing or decreasing release of this important hormone, and thereby have provided opportunities for influencing lactation, growth of mammary and pituitary tumors and other tissues responsive to prolactin."}
{"id": "PMID:19949", "title": "Effect of the diphosphonate EHDP on plasma inorganic phosphate and hemoglobin oxygen affinity of diabetic and healthy subjects.", "content": "The effect of oral disodium ethane-1-hydroxy-1,1-diphosphonate, EHDP (20 mg kg-1 day-1) and placebo given for 28 days on plasma inorganic phosphate (Pi) red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin was evaluated in 14 insulin-treated diabetics and 5 healthy volunteers. EHDP significantly increased mean Pi (diabetics: 1.18 to 1.67 mmol/l, p less than 0.01, controls: 1.03 to 1.71 mmol/l, p less than 0.02) and P50 at in vivo pH of the oxyhemoglobin dissociation curve (diabetics: 25.4 to 26.6 mmHg, p less than 0.02; controls: 26.3 to 28.9 mmHg, p less than 0.02). Pi and P50 were correlated in both diabetics and in controls (p less than 0.05). 2,3-DPG increased when the diabetics were on EHDP (p less than 0.005). The study emphasizes the importance of Pi on red cell function and indicates that an elevation of Pi tends to counteract the defect in oxygen release capacity of the red cells in diabetic subjects.", "contents": "Effect of the diphosphonate EHDP on plasma inorganic phosphate and hemoglobin oxygen affinity of diabetic and healthy subjects. The effect of oral disodium ethane-1-hydroxy-1,1-diphosphonate, EHDP (20 mg kg-1 day-1) and placebo given for 28 days on plasma inorganic phosphate (Pi) red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin was evaluated in 14 insulin-treated diabetics and 5 healthy volunteers. EHDP significantly increased mean Pi (diabetics: 1.18 to 1.67 mmol/l, p less than 0.01, controls: 1.03 to 1.71 mmol/l, p less than 0.02) and P50 at in vivo pH of the oxyhemoglobin dissociation curve (diabetics: 25.4 to 26.6 mmHg, p less than 0.02; controls: 26.3 to 28.9 mmHg, p less than 0.02). Pi and P50 were correlated in both diabetics and in controls (p less than 0.05). 2,3-DPG increased when the diabetics were on EHDP (p less than 0.005). The study emphasizes the importance of Pi on red cell function and indicates that an elevation of Pi tends to counteract the defect in oxygen release capacity of the red cells in diabetic subjects."}
{"id": "PMID:19952", "title": "Prolactin release inhibiting and stimulating factors in the hypothalamus.", "content": "Catecholamines, especially norepinephrine and dopamine, as well as GABA extracted from porcine hypothalamic tissue, were found to possess PIF activity in vitro. However, more work is needed to determine whether or not the effects of GABA or catecholamines on prolactin release are physiological or pharmacological. Until such studies are completed and until the chemical nature and biological roles of other substances with PIF activity found in the hypothalamus are clarified, no conclusion as to the nature of the physiological inhibitor of prolactin release should be made.", "contents": "Prolactin release inhibiting and stimulating factors in the hypothalamus. Catecholamines, especially norepinephrine and dopamine, as well as GABA extracted from porcine hypothalamic tissue, were found to possess PIF activity in vitro. However, more work is needed to determine whether or not the effects of GABA or catecholamines on prolactin release are physiological or pharmacological. Until such studies are completed and until the chemical nature and biological roles of other substances with PIF activity found in the hypothalamus are clarified, no conclusion as to the nature of the physiological inhibitor of prolactin release should be made."}
{"id": "PMID:19953", "title": "Atypical (relaxant) response to histamine in cat bronchus.", "content": "Histamine, 2-methylhistamine (a specific H1-receptor agonist), 4-methylhistamine (a specific H2-receptor agonist), isoprenaline, bradykinin, prostaglandin E1, E2, and F 2alpha  induce relaxation of carbachol-contracted isolated cat bronchial strips and tracheal chains. Bovine SRS-A contracts bronchus but not trachea. Histamine-induced relaxation of cat bronchus is not blocked by mepyramine (a specific H1-receptor antagonist); metiamide or burimamide (specific H2-receptor antagonists); propranolol ( a beta-adrenoceptor blocker) and indomethacin (a PG-synthetase inhibitor) suggesting non-participation of H1,H2-histamine receptors, beta-adrenoceptors (catecholamine release) and prostaglandin release in histamine-induced broncho-relaxations in the cat. The existence of an atypical histamine response, resistant to both H1- and H2-receptor antagonists is thus established in cat bronchus.", "contents": "Atypical (relaxant) response to histamine in cat bronchus. Histamine, 2-methylhistamine (a specific H1-receptor agonist), 4-methylhistamine (a specific H2-receptor agonist), isoprenaline, bradykinin, prostaglandin E1, E2, and F 2alpha  induce relaxation of carbachol-contracted isolated cat bronchial strips and tracheal chains. Bovine SRS-A contracts bronchus but not trachea. Histamine-induced relaxation of cat bronchus is not blocked by mepyramine (a specific H1-receptor antagonist); metiamide or burimamide (specific H2-receptor antagonists); propranolol ( a beta-adrenoceptor blocker) and indomethacin (a PG-synthetase inhibitor) suggesting non-participation of H1,H2-histamine receptors, beta-adrenoceptors (catecholamine release) and prostaglandin release in histamine-induced broncho-relaxations in the cat. The existence of an atypical histamine response, resistant to both H1- and H2-receptor antagonists is thus established in cat bronchus."}
{"id": "PMID:19954", "title": "Tick-borne diseases in the United States: Rocky Mountain spotted fever and Colorado tick fever. A review.", "content": "The historical, clinical, ecological, and epidemiological features of Rocky Mountain spotted fever and Colorado tick fever, the two important tick-borne diseases in the United States, are reviewed. Rocky Mountain spotted fever, once considered a disease of the past, has again become a measurable public health problem. Its nationwide incidence has steadily increased since 1960 and has reached record proportions in 1976. The various factors responsible for this trend as well as for the mortality rates, which in spite of availability of effective antibiotics ranges from 5 to 10%, are discussed. Education of the public about ticks and their potential role as vectors of Rickettsia rickettsii and/or Colorado tick fever virus, and about the clinical manifestations of Rocky Mountain spotted fever, is considered the best means for preventing high incidence and mortality from these diseases.", "contents": "Tick-borne diseases in the United States: Rocky Mountain spotted fever and Colorado tick fever. A review. The historical, clinical, ecological, and epidemiological features of Rocky Mountain spotted fever and Colorado tick fever, the two important tick-borne diseases in the United States, are reviewed. Rocky Mountain spotted fever, once considered a disease of the past, has again become a measurable public health problem. Its nationwide incidence has steadily increased since 1960 and has reached record proportions in 1976. The various factors responsible for this trend as well as for the mortality rates, which in spite of availability of effective antibiotics ranges from 5 to 10%, are discussed. Education of the public about ticks and their potential role as vectors of Rickettsia rickettsii and/or Colorado tick fever virus, and about the clinical manifestations of Rocky Mountain spotted fever, is considered the best means for preventing high incidence and mortality from these diseases."}
{"id": "PMID:19955", "title": "Influences of blood digestion on the development of Plasmodium gallinaceum (Brumpt) in the midgut of Aedes aegypti (L.).", "content": "Blood digestion of Aedes aegypti and development of Plasmodium gallinaceum were shifted against each other by giving the mosquitoes two consecutive blood meals. In this way the parasites were exposed to an environment where blood digestion was more advanced than in single blood meals. This procedure had an inhibiting effect on oocyst production when the two blood meals overlapped; an enhancing effect when they were well separated. The results are explained by the action of trypsin-like proteases on the parasites and indicate that plasmodia 0-10 h after blood meal are more sensitive to the enzymes than later stages of the parasites.", "contents": "Influences of blood digestion on the development of Plasmodium gallinaceum (Brumpt) in the midgut of Aedes aegypti (L.). Blood digestion of Aedes aegypti and development of Plasmodium gallinaceum were shifted against each other by giving the mosquitoes two consecutive blood meals. In this way the parasites were exposed to an environment where blood digestion was more advanced than in single blood meals. This procedure had an inhibiting effect on oocyst production when the two blood meals overlapped; an enhancing effect when they were well separated. The results are explained by the action of trypsin-like proteases on the parasites and indicate that plasmodia 0-10 h after blood meal are more sensitive to the enzymes than later stages of the parasites."}
{"id": "PMID:19957", "title": "Regulation of aerobic fermentation in protozoans. VI Comparative biochemistry of pathogenic and nonpathogenic protozoans.", "content": "We have investigated the oxidation of carbohydrate by several protozoan organisms. The oxidation is incomplete and results in a mixture of organic acid and carbon dioxide. The phosphofructokinase and pyruvate kinase, enzymes normally under strict metabolic regulation, are not subject to the normal feedback inhibition or activation mechanisms found in other cells. Moreover, our investigations and those of others support the hypothesis that a primary pathway for glucose metabolism is to phosphoenolpyruvic acid and then to oxalacetic acid with subsequent reduction to succinic acid.", "contents": "Regulation of aerobic fermentation in protozoans. VI Comparative biochemistry of pathogenic and nonpathogenic protozoans. We have investigated the oxidation of carbohydrate by several protozoan organisms. The oxidation is incomplete and results in a mixture of organic acid and carbon dioxide. The phosphofructokinase and pyruvate kinase, enzymes normally under strict metabolic regulation, are not subject to the normal feedback inhibition or activation mechanisms found in other cells. Moreover, our investigations and those of others support the hypothesis that a primary pathway for glucose metabolism is to phosphoenolpyruvic acid and then to oxalacetic acid with subsequent reduction to succinic acid."}
{"id": "PMID:19958", "title": "Physiologic interactions between L-proline and D-glucose in Leishmania tarentolae, L. donovani and Trypanosoma scelopori culture forms.", "content": "L-proline is more completely catabolized by Leishmania tarentolae and Trypanosoma scelopori than by L. donovani. In the two former organisms the activity of 14CO2 derived from L-proline-14C was as high or higher than that derived from D-glucose-14C; in L. donovani more 14CO2 is derived from D-glucose-14C than from L-proline-14C. Addition of unlabeled D-glucose to cells incubated with L-proline-14C resulted in increased 14C-activity of TCA-soluble fractions of L. tarentolae and T. scelopori; 14C-activity of 5% TCA insoluble fractions of these cells remained unchanged. Some of the increased 14C-label found in the soluble fraction was in glutamate and aspartate. This increased activity in glutamate and aspartate was accompanied by a decrease in alanine-14C in the free amino acid pool. These results suggest that there are complex physiological interactions between glucose and proline in the metabolism of L. tarentolae, L. donovani and T. scelopori. In addition, proline appears to have a more central role in the amino acid metabolism of L. tarentolae and T. scelopori whereas glucose may be more significant in L. donovani.", "contents": "Physiologic interactions between L-proline and D-glucose in Leishmania tarentolae, L. donovani and Trypanosoma scelopori culture forms. L-proline is more completely catabolized by Leishmania tarentolae and Trypanosoma scelopori than by L. donovani. In the two former organisms the activity of 14CO2 derived from L-proline-14C was as high or higher than that derived from D-glucose-14C; in L. donovani more 14CO2 is derived from D-glucose-14C than from L-proline-14C. Addition of unlabeled D-glucose to cells incubated with L-proline-14C resulted in increased 14C-activity of TCA-soluble fractions of L. tarentolae and T. scelopori; 14C-activity of 5% TCA insoluble fractions of these cells remained unchanged. Some of the increased 14C-label found in the soluble fraction was in glutamate and aspartate. This increased activity in glutamate and aspartate was accompanied by a decrease in alanine-14C in the free amino acid pool. These results suggest that there are complex physiological interactions between glucose and proline in the metabolism of L. tarentolae, L. donovani and T. scelopori. In addition, proline appears to have a more central role in the amino acid metabolism of L. tarentolae and T. scelopori whereas glucose may be more significant in L. donovani."}
{"id": "PMID:19959", "title": "Tricarboxylic acid and glyoxylate cycles in the Leishmaniae.", "content": "Cell-free extacts of four species of Leishmania (L. brasiliensis, L. donovani, L. mexicana and L. tropica) have been shown to contain all enzymes of the tricarboxylic acid cycle. However, the activity of citrate synthase is so low that it is doubtful whether this pathway is of significance in the metabolism of carbohydrate substrates. All four species show the presence of the two enzymes (isocitrate lyase and malate synthase) characteristic of the glyoxylate bypass and glyoxylate is present in cell-free preparations. The isocitrate lyase is relatively insensitive to phosphoenolpyruvate (PEP). The glyoxylate cycle in the Leishmaniae, thus, seems to be independent of control by C3 compounds.", "contents": "Tricarboxylic acid and glyoxylate cycles in the Leishmaniae. Cell-free extacts of four species of Leishmania (L. brasiliensis, L. donovani, L. mexicana and L. tropica) have been shown to contain all enzymes of the tricarboxylic acid cycle. However, the activity of citrate synthase is so low that it is doubtful whether this pathway is of significance in the metabolism of carbohydrate substrates. All four species show the presence of the two enzymes (isocitrate lyase and malate synthase) characteristic of the glyoxylate bypass and glyoxylate is present in cell-free preparations. The isocitrate lyase is relatively insensitive to phosphoenolpyruvate (PEP). The glyoxylate cycle in the Leishmaniae, thus, seems to be independent of control by C3 compounds."}
{"id": "PMID:19960", "title": "Problems in the comparative physiology of some trypanosomatid flagellates.", "content": "There is considerable evidence that trypanosomatid species vary in their metabolic characteristics, that they vary in the mechanisms by which they control these characteristics, and that a single species may vary metabolically without varying structurally. Studies to date from a number of laboratories also indicate there is still reason to believe that metabolic characteristics of trypanosomatid flagellates, as manifest in culture, are at least correlated (in some cases) with the behavior of the flagellate species in the metazoan host. It appears that our major tasks for the next several years are 1. to discover the extent to which these correlations are manifestations of characteristics required for life in the metazoan host, 2. to discover the extent to which these correlations are manifestations of characteristics which determine infection site within the metazoan host, 3. to discover which if any metabolic control mechanisms contribute to the multiplicity of clinical infections often seen in this group of protozoa, and 4. to discover the critical links between energy metabolism, the control of that metabolism, and life inside a host or host cell.", "contents": "Problems in the comparative physiology of some trypanosomatid flagellates. There is considerable evidence that trypanosomatid species vary in their metabolic characteristics, that they vary in the mechanisms by which they control these characteristics, and that a single species may vary metabolically without varying structurally. Studies to date from a number of laboratories also indicate there is still reason to believe that metabolic characteristics of trypanosomatid flagellates, as manifest in culture, are at least correlated (in some cases) with the behavior of the flagellate species in the metazoan host. It appears that our major tasks for the next several years are 1. to discover the extent to which these correlations are manifestations of characteristics required for life in the metazoan host, 2. to discover the extent to which these correlations are manifestations of characteristics which determine infection site within the metazoan host, 3. to discover which if any metabolic control mechanisms contribute to the multiplicity of clinical infections often seen in this group of protozoa, and 4. to discover the critical links between energy metabolism, the control of that metabolism, and life inside a host or host cell."}
{"id": "PMID:19965", "title": "Testicular venography in the nonpalpable testis.", "content": "Localization and identification of a nonpalpable testis can be done accurately by testicular venography. The identification of the pampiniform plexus is essential to the localization of the testis by this method. We evaluated 15 patients 3-39 years of age with 21 nonpalpable testes. Fourteen successful testicular venograms were performed showing four retroperitoneal testes, four testes within the inguinal canal, and two testes located in the superficial inguinal pouch. Three nonpalpable testes were thought to be due to true agenesis, and one venogram was performed after prior surgical removal of the testis. Catheterization of the left testicular vein was accomplished with greater ease and accuracy (79%) to the right side (42%).", "contents": "Testicular venography in the nonpalpable testis. Localization and identification of a nonpalpable testis can be done accurately by testicular venography. The identification of the pampiniform plexus is essential to the localization of the testis by this method. We evaluated 15 patients 3-39 years of age with 21 nonpalpable testes. Fourteen successful testicular venograms were performed showing four retroperitoneal testes, four testes within the inguinal canal, and two testes located in the superficial inguinal pouch. Three nonpalpable testes were thought to be due to true agenesis, and one venogram was performed after prior surgical removal of the testis. Catheterization of the left testicular vein was accomplished with greater ease and accuracy (79%) to the right side (42%)."}
{"id": "PMID:19966", "title": "Polyarteritis nodosa and hepatitis-B surface antigen: role of angiography in diagnosis.", "content": "two patients with polyarteritis nodosa who presented with vague constitutional systems and hepatitis-B antigenemia are reported. Angiography was used as the primary diagnostic procedure and confirmed the diagnosis in each case. Angiography is a relatively simple and direct means for establishing the diagnosis of polyarteritis nodosa. In these patients, the typical finding of aneurysm formation in multiple organs was observed. Arterial narrowing was also widespread. Multiple renal infarcts are shown in one case, and bronchial arteriography revealed aneurysms and narrowing in bronchial and intercostal arteries in one patient who had a recent pulmonary infarction and a normal pulmonary arteriogram. The relationship of the hepatitis-B antigen and polyarteritis is also emphasized.", "contents": "Polyarteritis nodosa and hepatitis-B surface antigen: role of angiography in diagnosis. two patients with polyarteritis nodosa who presented with vague constitutional systems and hepatitis-B antigenemia are reported. Angiography was used as the primary diagnostic procedure and confirmed the diagnosis in each case. Angiography is a relatively simple and direct means for establishing the diagnosis of polyarteritis nodosa. In these patients, the typical finding of aneurysm formation in multiple organs was observed. Arterial narrowing was also widespread. Multiple renal infarcts are shown in one case, and bronchial arteriography revealed aneurysms and narrowing in bronchial and intercostal arteries in one patient who had a recent pulmonary infarction and a normal pulmonary arteriogram. The relationship of the hepatitis-B antigen and polyarteritis is also emphasized."}
{"id": "PMID:19968", "title": "Improved quality control of blood acid-base equilibrium using the daily mean of patients' results: a validation study.", "content": "The efficiency of the daily mean of patients' results as a quality control tool for acid-base equilibrium has been studied in three one-month periods. Results for the first two periods were obtained in a stable patient population using tonometry in one period, direct measurement of PCO2 in the other; the third period corresponded to another patient population in which PCO2 was determined by direct measurement. These comparisons allowed demonstration that both methodology and patient populations influenced the optimal truncation limits used to exclude extreme values. Furthermore, the efficiency of the daily mean in itself was poor. Using a cusum plot of the differences of each daily mean from the monthly mean of the daily means, however, dramatically improved this efficiency. So modified, quality control using the daily mean of patients' results represents a useful tool, since the whole analytic process, from blood sampling to result, is checked.", "contents": "Improved quality control of blood acid-base equilibrium using the daily mean of patients' results: a validation study. The efficiency of the daily mean of patients' results as a quality control tool for acid-base equilibrium has been studied in three one-month periods. Results for the first two periods were obtained in a stable patient population using tonometry in one period, direct measurement of PCO2 in the other; the third period corresponded to another patient population in which PCO2 was determined by direct measurement. These comparisons allowed demonstration that both methodology and patient populations influenced the optimal truncation limits used to exclude extreme values. Furthermore, the efficiency of the daily mean in itself was poor. Using a cusum plot of the differences of each daily mean from the monthly mean of the daily means, however, dramatically improved this efficiency. So modified, quality control using the daily mean of patients' results represents a useful tool, since the whole analytic process, from blood sampling to result, is checked."}
{"id": "PMID:19969", "title": "New method of obtaining cinchophen ulcer in dogs.", "content": "Cinchophen injected into the cerebral ventricle reacted with the hypothalamus somewhere in the vicinity ventricle, and produced a release of ACTH as indicated by a rise in peripheral plasma 11-OHCS concentration in the dog. The amount of cinchophen injected into the ventricle corresponds to about 1/600 of the dose required to produce the same effect by the intravenous route. Repeated intraventricular injections of cinchophen were effective in producing gastric erosions and ulcers at smaller doses than the intravenous one (1/100 and 1/400). Damage to the gastric wall might be due to a mechanism involving a localized portion of the hypothalamus and/or via a cerebral ventricle. Bilateral truncal vagotomy did not have any effect on chronic ulcer production. The cinchophen ulcerations were accompanied by an increase in plasma corticosteroids. The new experimental technique for producing peptic ulcer in dogs via a central neurohumoral mechanism is described.", "contents": "New method of obtaining cinchophen ulcer in dogs. Cinchophen injected into the cerebral ventricle reacted with the hypothalamus somewhere in the vicinity ventricle, and produced a release of ACTH as indicated by a rise in peripheral plasma 11-OHCS concentration in the dog. The amount of cinchophen injected into the ventricle corresponds to about 1/600 of the dose required to produce the same effect by the intravenous route. Repeated intraventricular injections of cinchophen were effective in producing gastric erosions and ulcers at smaller doses than the intravenous one (1/100 and 1/400). Damage to the gastric wall might be due to a mechanism involving a localized portion of the hypothalamus and/or via a cerebral ventricle. Bilateral truncal vagotomy did not have any effect on chronic ulcer production. The cinchophen ulcerations were accompanied by an increase in plasma corticosteroids. The new experimental technique for producing peptic ulcer in dogs via a central neurohumoral mechanism is described."}
{"id": "PMID:19971", "title": "Blunted respiratory drive in congenital myopathy.", "content": "Two patients with clinically mild congenital myopathies presented with chronic respiratory failure. Muscle weakness alone could not account for the respiratory insufficiency since static respiratory pressures were not markedly impaired, ventilation during exercise was normal, and daytime ventilation was normal if ventilatory assistance was provided at night. The ventilatory responses to inhaled carbon dioxide were very low, suggesting that impairment of the central nervous respiratory chemoreceptor contributed to hypoventilation. These patients and others described in the literature suggest that central depression of ventilation may occur more frequently than previously recognized in patients with muscular disorders. Patients with chronic respiratory failure due to central depression of respiratory drive can be effectively managed by assisted ventilation at night.", "contents": "Blunted respiratory drive in congenital myopathy. Two patients with clinically mild congenital myopathies presented with chronic respiratory failure. Muscle weakness alone could not account for the respiratory insufficiency since static respiratory pressures were not markedly impaired, ventilation during exercise was normal, and daytime ventilation was normal if ventilatory assistance was provided at night. The ventilatory responses to inhaled carbon dioxide were very low, suggesting that impairment of the central nervous respiratory chemoreceptor contributed to hypoventilation. These patients and others described in the literature suggest that central depression of ventilation may occur more frequently than previously recognized in patients with muscular disorders. Patients with chronic respiratory failure due to central depression of respiratory drive can be effectively managed by assisted ventilation at night."}
{"id": "PMID:19975", "title": "Fetal respiration. A review.", "content": "During recent years respiratory movements by the human fetus have been rediscovered. The types of movements have been defined, and their dependence on some physiologic conditions has been described. Pharmacologic agents influence not only the occurrence of the movements but also their rate and depth. A tidal flow of fluid between lung and amnionic sac has been established, which may play an important role in lung development. Demonstration of this route for exchange of water and soluble substances identifies the lung as an organ very likely involved in exchange between fetal compartments. Additionally, the deposition in the lung of the particulate matter contained in amnionic fluid may not be proof of pathologic aspiration as previously thought.", "contents": "Fetal respiration. A review. During recent years respiratory movements by the human fetus have been rediscovered. The types of movements have been defined, and their dependence on some physiologic conditions has been described. Pharmacologic agents influence not only the occurrence of the movements but also their rate and depth. A tidal flow of fluid between lung and amnionic sac has been established, which may play an important role in lung development. Demonstration of this route for exchange of water and soluble substances identifies the lung as an organ very likely involved in exchange between fetal compartments. Additionally, the deposition in the lung of the particulate matter contained in amnionic fluid may not be proof of pathologic aspiration as previously thought."}
{"id": "PMID:19979", "title": "Functional male dyspareunia: a case study.", "content": "An apparently successful treatment of a male with a long history of dyspareunia is discussed. The case is unique not only because the subject was male but also in that the etiology was functional. The case demonstrates the multicausal nature of dyspareunia as well as the need for an approach utilizing both a psychodynamic and behavioral methodology.", "contents": "Functional male dyspareunia: a case study. An apparently successful treatment of a male with a long history of dyspareunia is discussed. The case is unique not only because the subject was male but also in that the etiology was functional. The case demonstrates the multicausal nature of dyspareunia as well as the need for an approach utilizing both a psychodynamic and behavioral methodology."}
{"id": "PMID:19982", "title": "The thin-layer isoelectric focusing of lactate dehydrogenase isoenzymes in rabbit lens parts and in intraocular tissues.", "content": "Lactate dehydrogenase (LDH) isoenzymes of rabbit lens and other intraocular tissues are separated by thin-layer isoelectric focusing and localized as discrete groups of multiple bands with defined isoelectric points after staining by the tetrazolium method. In the rabbit lens parts, the predominant isoenzymes are LDH-4 and LDH-5. The bands show microheterogeneity, are composed of 2-4 subcomponents, and the pattern shows a distribution of the liver type. The activity of the LDH-4 decreases and that of LDH-5 increases in an order given by the equator, anterior and posterior cortex, and nucleus. LDH-3 remains almost constant in all lens parts. LDH-4 is composed of two subcomponents, one of which, the most cathodic with higher isoelectric point, is almost absent in the lens nucleus. Of the LDH localized in the rabbit intraocular tissues, only the retina shows a pattern of five isoenzymes also of the liver type. In all intraocular tissues LDH-3, -4, and -5 are very prominent, show also microheterogeneity of their isoenzyme bands, and are each composed of 4-6 subcomponents. LDH-1 and -2 show only one isofocused component. Species specificity is shown of the LDH isoenzymes in the rabbit, mouse, dog, and calf lens.", "contents": "The thin-layer isoelectric focusing of lactate dehydrogenase isoenzymes in rabbit lens parts and in intraocular tissues. Lactate dehydrogenase (LDH) isoenzymes of rabbit lens and other intraocular tissues are separated by thin-layer isoelectric focusing and localized as discrete groups of multiple bands with defined isoelectric points after staining by the tetrazolium method. In the rabbit lens parts, the predominant isoenzymes are LDH-4 and LDH-5. The bands show microheterogeneity, are composed of 2-4 subcomponents, and the pattern shows a distribution of the liver type. The activity of the LDH-4 decreases and that of LDH-5 increases in an order given by the equator, anterior and posterior cortex, and nucleus. LDH-3 remains almost constant in all lens parts. LDH-4 is composed of two subcomponents, one of which, the most cathodic with higher isoelectric point, is almost absent in the lens nucleus. Of the LDH localized in the rabbit intraocular tissues, only the retina shows a pattern of five isoenzymes also of the liver type. In all intraocular tissues LDH-3, -4, and -5 are very prominent, show also microheterogeneity of their isoenzyme bands, and are each composed of 4-6 subcomponents. LDH-1 and -2 show only one isofocused component. Species specificity is shown of the LDH isoenzymes in the rabbit, mouse, dog, and calf lens."}
{"id": "PMID:19985", "title": "The effectiveness and duration of preoperative antacid therapy.", "content": "The administration of 10 ml of magnesium trisilicate mixture to premedicated patients, maintains the pH of gastric contents below pH 2-5 during subsequent general anaesthesia. This effect was sustained for over seven hours--the longest anaesthetic time studied. No antacid supplementation is required to offer protection from acid aspiration during emergence and initial recovery from general anaesthesia.", "contents": "The effectiveness and duration of preoperative antacid therapy. The administration of 10 ml of magnesium trisilicate mixture to premedicated patients, maintains the pH of gastric contents below pH 2-5 during subsequent general anaesthesia. This effect was sustained for over seven hours--the longest anaesthetic time studied. No antacid supplementation is required to offer protection from acid aspiration during emergence and initial recovery from general anaesthesia."}
{"id": "PMID:19986", "title": "The effect of hyoscine and atropine on the lower oesophageal sphincter.", "content": "The effects of intravenous hyoscine 0-4 mg and atropine 0-6 mg on lower oesophageal sphincter tone were studied in normal human subjects. Hyoscine and atropine both decreased the lower oesophageal sphincter (L.O.S) pressure by approximately 11 cm H2O (p less than 0-01). There was also an increased incidence of reflux as seen by an indwelling pH electrode in the lower oesophagus. These findings are relevant to the preoperative preparation of patients presenting for emergency obstetrical anaesthesia; since gastro-oesophagus reflux and pulmonary aspiration of acid gastric content continues to be a significant cause of morbidity and mortality.", "contents": "The effect of hyoscine and atropine on the lower oesophageal sphincter. The effects of intravenous hyoscine 0-4 mg and atropine 0-6 mg on lower oesophageal sphincter tone were studied in normal human subjects. Hyoscine and atropine both decreased the lower oesophageal sphincter (L.O.S) pressure by approximately 11 cm H2O (p less than 0-01). There was also an increased incidence of reflux as seen by an indwelling pH electrode in the lower oesophagus. These findings are relevant to the preoperative preparation of patients presenting for emergency obstetrical anaesthesia; since gastro-oesophagus reflux and pulmonary aspiration of acid gastric content continues to be a significant cause of morbidity and mortality."}
{"id": "PMID:19987", "title": "An anaphylactoid reaction to gallamine triethiodide.", "content": "A patient suffered profound anaphylactoid reaction during anaesthesia. Intradermal skin testing confirmed the clinical impression that gallamine caused the reaction. The method of testing is discussed. Previous reports of hypersensitivity to the drug are reviewed, and the use of adrenaline, antihistamines and corticosteroids in patient management are considered.", "contents": "An anaphylactoid reaction to gallamine triethiodide. A patient suffered profound anaphylactoid reaction during anaesthesia. Intradermal skin testing confirmed the clinical impression that gallamine caused the reaction. The method of testing is discussed. Previous reports of hypersensitivity to the drug are reviewed, and the use of adrenaline, antihistamines and corticosteroids in patient management are considered."}
{"id": "PMID:20002", "title": "[The Bain anesthetic system in facial surgery].", "content": "The BAIN circuit was studied in 11 patients undergoing maxillofacial surgery, with no respiratory deficit, and under spontaneous and assisted ventilation, with a rate of flow of gas of 80, 100, 120, 140 ml/kg/min. From the results it could be concluded that this circuit should be used with a flow of at least 140 ml/kg/min, in assisted ventilation, in order to avoid any retention of CO2. Capnographic follow-up enabled better regulation of the flow rate necessary.", "contents": "[The Bain anesthetic system in facial surgery]. The BAIN circuit was studied in 11 patients undergoing maxillofacial surgery, with no respiratory deficit, and under spontaneous and assisted ventilation, with a rate of flow of gas of 80, 100, 120, 140 ml/kg/min. From the results it could be concluded that this circuit should be used with a flow of at least 140 ml/kg/min, in assisted ventilation, in order to avoid any retention of CO2. Capnographic follow-up enabled better regulation of the flow rate necessary."}
{"id": "PMID:20004", "title": "[Anesthesia with continuous infusion of alfatesine and phenoperidine. Uses in anesthesia of aged subjects in visceral surgery].", "content": "Anaesthesia was administered to one hundred and fifty eight patients by continuous infusion of a mixture of Alfatesine and phenoperidine. The patients were divided on two groups: group A consisted in 96 patients undergoing abdominal surgery and group B of 62 cases of various types of surgery, mainly orthopedics. The average age was 63 years (range 16-96). The operative risk scored 6 or more in 71 cases. The length of operation averaged 151 minutes (S.D. +/- 15). The mixture made of alfadione 25 ml and phenoperidine 5 mg in a glucose 5 per cent 250 ml solution was administered by mechanical pump. The induction dose was 50 ml of the mixture for patients under 50 years (rate 10 ml per minute), 40 ml per patients from 50 to 70 years (5 ml per minute), and 30 ml for patients over 70 years (5 ml per minute). The maintenance dose was adjusted to weight and age and ranged from 0,11 to 0,15 ml/kg/h for alfadione and from 0,022 to 0,030 mg/kg/h for phenoperidine. Routine tracheal intubation and artificial ventilation were performed in group A. The results are studied in relation to the effectiveness of the anaesthesia mixture, its side effects and influence on recovery. Generally, the results are good and emphasize the value of the technic in abdominal surgery for elderly patients. The methods of application are discussed in terms of medical background.", "contents": "[Anesthesia with continuous infusion of alfatesine and phenoperidine. Uses in anesthesia of aged subjects in visceral surgery]. Anaesthesia was administered to one hundred and fifty eight patients by continuous infusion of a mixture of Alfatesine and phenoperidine. The patients were divided on two groups: group A consisted in 96 patients undergoing abdominal surgery and group B of 62 cases of various types of surgery, mainly orthopedics. The average age was 63 years (range 16-96). The operative risk scored 6 or more in 71 cases. The length of operation averaged 151 minutes (S.D. +/- 15). The mixture made of alfadione 25 ml and phenoperidine 5 mg in a glucose 5 per cent 250 ml solution was administered by mechanical pump. The induction dose was 50 ml of the mixture for patients under 50 years (rate 10 ml per minute), 40 ml per patients from 50 to 70 years (5 ml per minute), and 30 ml for patients over 70 years (5 ml per minute). The maintenance dose was adjusted to weight and age and ranged from 0,11 to 0,15 ml/kg/h for alfadione and from 0,022 to 0,030 mg/kg/h for phenoperidine. Routine tracheal intubation and artificial ventilation were performed in group A. The results are studied in relation to the effectiveness of the anaesthesia mixture, its side effects and influence on recovery. Generally, the results are good and emphasize the value of the technic in abdominal surgery for elderly patients. The methods of application are discussed in terms of medical background."}
{"id": "PMID:20005", "title": "[Action of dibencozide on nitrogen metabolism in immediate and long-term postoperative resuscitation].", "content": "The catabolic orientation of the immediate post-aggression phase is aggravated in neurosurgery by the almost routine prescription of corticosteroids. This emphasises the value of any treatment which might limit this orientation. The authors report their experience with the use of dibencozide, with its known facilitating action upon nitrogen assimilation, in the absence of any side effects.", "contents": "[Action of dibencozide on nitrogen metabolism in immediate and long-term postoperative resuscitation]. The catabolic orientation of the immediate post-aggression phase is aggravated in neurosurgery by the almost routine prescription of corticosteroids. This emphasises the value of any treatment which might limit this orientation. The authors report their experience with the use of dibencozide, with its known facilitating action upon nitrogen assimilation, in the absence of any side effects."}
{"id": "PMID:20006", "title": "[Percutaneous catheterization of the subclavian vein and/or the Pirogoff angle].", "content": "The approach to the sub-clavian venous axis being carried out blindly, the difficulties encountered oblige one: - to avoid the danger (pleural dome in particular); - to guide the catheter along the sub-clavian axis (and not in the jugular vein) and therefore to know the anatomical landmarks and a precise method. A variant of the CARLE technique, that which is proposed is based on no other anatomical argument than the direction of the sub-clavian axis and of its junction. The puncture site is higher and more external, a guiding finger shows the pathway in such a way as to try and leave the dangers behind the pathway of the needle. The obligatory long tunnelization of the catheter, becomes an advantage (fights against the danger of infection) to be added to the already known advantages of this pathway.", "contents": "[Percutaneous catheterization of the subclavian vein and/or the Pirogoff angle]. The approach to the sub-clavian venous axis being carried out blindly, the difficulties encountered oblige one: - to avoid the danger (pleural dome in particular); - to guide the catheter along the sub-clavian axis (and not in the jugular vein) and therefore to know the anatomical landmarks and a precise method. A variant of the CARLE technique, that which is proposed is based on no other anatomical argument than the direction of the sub-clavian axis and of its junction. The puncture site is higher and more external, a guiding finger shows the pathway in such a way as to try and leave the dangers behind the pathway of the needle. The obligatory long tunnelization of the catheter, becomes an advantage (fights against the danger of infection) to be added to the already known advantages of this pathway."}
{"id": "PMID:20007", "title": "[A case of acute ischemia of the extremities in disseminated intravascular coagulation in an infant].", "content": "The authors report a case of diffuse intravascular coagulation occurring in a 15 day old infant suffering from several congenital malformations (meningocoele, megacolon and bilateral hydronephrosis). During reparative surgery, acute and symmetrical of the lower limbs developed in a context of shock and respiratory distress. Associated with a coagulopathy, it progressed towards the death of the child on the second postoperative day. The authors review the cases of gangrene of the extremities with diffuse intravascular coagulation occurring in the young child found in the literature, and discuss the factors which favourise its development.", "contents": "[A case of acute ischemia of the extremities in disseminated intravascular coagulation in an infant]. The authors report a case of diffuse intravascular coagulation occurring in a 15 day old infant suffering from several congenital malformations (meningocoele, megacolon and bilateral hydronephrosis). During reparative surgery, acute and symmetrical of the lower limbs developed in a context of shock and respiratory distress. Associated with a coagulopathy, it progressed towards the death of the child on the second postoperative day. The authors review the cases of gangrene of the extremities with diffuse intravascular coagulation occurring in the young child found in the literature, and discuss the factors which favourise its development."}
{"id": "PMID:20008", "title": "[Early respiratory involvement in burns. Mechanism and prognostic significance].", "content": "A retrospective study, on 87 flame burn patients, of arterial Pa02, chest X-ray and lactic dehydrogenase isoenzyme III revealed the very early onset (before the 24th hour) of severe respiratory problems. This involvement, with a severe prognostic significance, appears to be much more closely related to the extent of the cutaneous burn than to the inhalation of fumes or vapours, and seems to fall into the more general category of \"post-aggression lung\".", "contents": "[Early respiratory involvement in burns. Mechanism and prognostic significance]. A retrospective study, on 87 flame burn patients, of arterial Pa02, chest X-ray and lactic dehydrogenase isoenzyme III revealed the very early onset (before the 24th hour) of severe respiratory problems. This involvement, with a severe prognostic significance, appears to be much more closely related to the extent of the cutaneous burn than to the inhalation of fumes or vapours, and seems to fall into the more general category of \"post-aggression lung\"."}
{"id": "PMID:20009", "title": "[Ventilatory disorders in the acute period of tetraplegia of traumatic origin].", "content": "Out of a total of 30 cases of traumatic tetraplegia with the lesion situated from C1 to C8 seen during the acute phase in the department of Professor JUDET, 8 posed no respiratory problems, whilst the others suffered lobar or pulmonary atelectasis in 13 cases, retention of bronchial secretions with secondary infection in 6 cases and progressive hypoxaemia in 3 cases. The first two types of complication are mechanical in origin and are directly related to the neurological problem. The third type is of more complex pathogenesis, combining water retention, hypoproetinaemia and secondary infection.", "contents": "[Ventilatory disorders in the acute period of tetraplegia of traumatic origin]. Out of a total of 30 cases of traumatic tetraplegia with the lesion situated from C1 to C8 seen during the acute phase in the department of Professor JUDET, 8 posed no respiratory problems, whilst the others suffered lobar or pulmonary atelectasis in 13 cases, retention of bronchial secretions with secondary infection in 6 cases and progressive hypoxaemia in 3 cases. The first two types of complication are mechanical in origin and are directly related to the neurological problem. The third type is of more complex pathogenesis, combining water retention, hypoproetinaemia and secondary infection."}
{"id": "PMID:20010", "title": "[Atypical pulmonary embolism associated with inter-auricular communication].", "content": "A case of massive pulmonary embolism at a patient with undetected atrial defect is reported. The authors discuss the difficulties of establishing a proper diagnosis when the right heart pressure is not raised and when a large emboliser is well tolerated. Angiography confirmed the diagnosis and the patient was successfully treated with embolectomy followed by ligation of the inferior vena cava.", "contents": "[Atypical pulmonary embolism associated with inter-auricular communication]. A case of massive pulmonary embolism at a patient with undetected atrial defect is reported. The authors discuss the difficulties of establishing a proper diagnosis when the right heart pressure is not raised and when a large emboliser is well tolerated. Angiography confirmed the diagnosis and the patient was successfully treated with embolectomy followed by ligation of the inferior vena cava."}
{"id": "PMID:20011", "title": "[The cerebro-cardiac syndrome in neuro-traumatology].", "content": "Head trauma is a possible cause of E.C.G. modifications originating in the brain and unresponsive to pure symptomatic cardial therapy. On the other hand, these perturbations react in a favourable way to treatment aimed at protecting the heart against descending nociceptive influx caused by brain injury. This report shows the results of a retrospective electrographic study of 220 unoperated patients with head injuries aged 15 to 30 years. A correlation is established between E.C.G. findings and depth of coma. The authors discuss their findings and suggest an etiologic pathology based on clinical and experimental factors.", "contents": "[The cerebro-cardiac syndrome in neuro-traumatology]. Head trauma is a possible cause of E.C.G. modifications originating in the brain and unresponsive to pure symptomatic cardial therapy. On the other hand, these perturbations react in a favourable way to treatment aimed at protecting the heart against descending nociceptive influx caused by brain injury. This report shows the results of a retrospective electrographic study of 220 unoperated patients with head injuries aged 15 to 30 years. A correlation is established between E.C.G. findings and depth of coma. The authors discuss their findings and suggest an etiologic pathology based on clinical and experimental factors."}
{"id": "PMID:20013", "title": "Medullary carcinoma of the thyroid gland.", "content": "Out of the discovery of concurrent multiple endocrine neoplasms has evolved the concept of multiple endocrine adenomatosis (MEA1 and MEA2). Medullary carcinoma of the thyroid gland is the most constant facet of MEA2 and is derived from C-cells of the neural crest. These cells, resembling parafollicular cells of lower animals, elaborate calcitonin which acts as a sensitive signal of the presence of the tumor. Ninety per cent of MCT occurs sporadically; in 10% the tumor presents as an atuosomal dominant trait. Other endocrinopathies, especially pheochromocytomas, are present in 70% of cases. The lesions are \"cold\" on iodine radioisotope scan. On microscopic examination, the appearance of amyloid is characteristic. Regional lymph node metastasis occurs early. The tumor deserves appropriate aggressive management. Surgical therapy should begin early and vigorously with the minimum procedure being total thyroidectomy. Frequent lymph node metastasis speaks for the need for regional neck dissection extended into the superior mediastinum. The search for, and the treatment of, the frequently associated endocrinopathies is essential. Pheochromocytoma must be suspected and eradicated before treatment of the thyroid tumor. A genetic workup should be included.", "contents": "Medullary carcinoma of the thyroid gland. Out of the discovery of concurrent multiple endocrine neoplasms has evolved the concept of multiple endocrine adenomatosis (MEA1 and MEA2). Medullary carcinoma of the thyroid gland is the most constant facet of MEA2 and is derived from C-cells of the neural crest. These cells, resembling parafollicular cells of lower animals, elaborate calcitonin which acts as a sensitive signal of the presence of the tumor. Ninety per cent of MCT occurs sporadically; in 10% the tumor presents as an atuosomal dominant trait. Other endocrinopathies, especially pheochromocytomas, are present in 70% of cases. The lesions are \"cold\" on iodine radioisotope scan. On microscopic examination, the appearance of amyloid is characteristic. Regional lymph node metastasis occurs early. The tumor deserves appropriate aggressive management. Surgical therapy should begin early and vigorously with the minimum procedure being total thyroidectomy. Frequent lymph node metastasis speaks for the need for regional neck dissection extended into the superior mediastinum. The search for, and the treatment of, the frequently associated endocrinopathies is essential. Pheochromocytoma must be suspected and eradicated before treatment of the thyroid tumor. A genetic workup should be included."}
{"id": "PMID:20014", "title": "Extrinsic neural influences on gastrointestinal motility.", "content": "The gastrointestinal tract is capable of carrying on all its major functions after all extrinsic nerves have been cut. This automaticity is due to the local nervous mechanisms in the walls of the gastrointestinal tract and the inherent properties of the smooth muscles in its walls, and gastrointestinal hormones. All levels of the central nervous system have been shown, by stimulation and ablation studies, to influence the motility of the entire gastrointestinal tract. Throughout many cerebral areas there are loci which, on stimulation, exert both inhibitory, and less often, excitatory influence on gastrointestinal motility. These influences are mediated by sympathetic and parasympathetic visceral efferent nerves, as well as humoral agents from the neurohypophysis. Thus, they impose an influence of higher control on the automatically efficient intrinsic motility. They are guided by information received from visceral, cranial, and somatic afferents, as well as intracerebral, or psychic inputs. Under normal circumstances they only influence gastrointestinal activity as will best afford the optimal functioning of a performance done automatically with efficiency and finesse.", "contents": "Extrinsic neural influences on gastrointestinal motility. The gastrointestinal tract is capable of carrying on all its major functions after all extrinsic nerves have been cut. This automaticity is due to the local nervous mechanisms in the walls of the gastrointestinal tract and the inherent properties of the smooth muscles in its walls, and gastrointestinal hormones. All levels of the central nervous system have been shown, by stimulation and ablation studies, to influence the motility of the entire gastrointestinal tract. Throughout many cerebral areas there are loci which, on stimulation, exert both inhibitory, and less often, excitatory influence on gastrointestinal motility. These influences are mediated by sympathetic and parasympathetic visceral efferent nerves, as well as humoral agents from the neurohypophysis. Thus, they impose an influence of higher control on the automatically efficient intrinsic motility. They are guided by information received from visceral, cranial, and somatic afferents, as well as intracerebral, or psychic inputs. Under normal circumstances they only influence gastrointestinal activity as will best afford the optimal functioning of a performance done automatically with efficiency and finesse."}
{"id": "PMID:20015", "title": "The switch process in manic-depressive psychosis.", "content": "Bipolar manic-depressive illness is a chronic disease in which patients experience recurrent episodes of mania and depression. Patients often change from a nonverbal, retarded depression of many months' duration to a hyperactive, psychotic, manic condition during the switch. The time required for the switch from depression into mania varies from 5 minutes to a couple of days. Just before it happens, pateints experience marked insomnia and decreased rapid eye movement sleep. It is hypothesized that specific changes in brain monoamine metabolism precede the switch. Alterations in neurotransmitter metabolites, as measured in urine and cerebrospinal fluid, may precede and accompany it. The switch into mania can be precipitated by environmental stresses or by drugs that act by increasing functional brain monoamines. Drugs that reverse the manic state all share the common property of affecting biogenic amines. The switch  into mania is viewed in the context of a longitudinal cyclic process and may be further studied with specific pharmacologic agents that block drug-induced maniclike states in man.", "contents": "The switch process in manic-depressive psychosis. Bipolar manic-depressive illness is a chronic disease in which patients experience recurrent episodes of mania and depression. Patients often change from a nonverbal, retarded depression of many months' duration to a hyperactive, psychotic, manic condition during the switch. The time required for the switch from depression into mania varies from 5 minutes to a couple of days. Just before it happens, pateints experience marked insomnia and decreased rapid eye movement sleep. It is hypothesized that specific changes in brain monoamine metabolism precede the switch. Alterations in neurotransmitter metabolites, as measured in urine and cerebrospinal fluid, may precede and accompany it. The switch into mania can be precipitated by environmental stresses or by drugs that act by increasing functional brain monoamines. Drugs that reverse the manic state all share the common property of affecting biogenic amines. The switch  into mania is viewed in the context of a longitudinal cyclic process and may be further studied with specific pharmacologic agents that block drug-induced maniclike states in man."}
{"id": "PMID:20017", "title": "Ecology of Keystone virus, a transovarially maintained arbovirus.", "content": "Our studies in the Pocomoke Cypress Swamp of Maryland have shown that KEY strain of CE is endemic and is carried by the floodwater mosquito A. atlanticus. The virus is transmitted transstadially in nature, as evidenced by our recovery of virus from larvae and males of this species. Serologic evidence, both here and elsewhere, indicates that vertebrates are infected with KEY, but their role in the transmission cycle remains unknown. We have found several animals, for example, the gray squirrel, that are potential vertebrate reservoirs for the virus. Gray squirrels possess antibodies to KEY in nature, are known to be fed upon by A. atlanticus females, and have been shown to circulate a high-titered viremia after experimental inoculation. Evidence from 1974 collections, however, indicates that A. atlanticus females ingested only a single blood meal during the period when adults were active. We will not be able to assess the relative importance of the vertebrate and mosquito cycles until much more work has been performed on vector-reservoir-virus dynamics.", "contents": "Ecology of Keystone virus, a transovarially maintained arbovirus. Our studies in the Pocomoke Cypress Swamp of Maryland have shown that KEY strain of CE is endemic and is carried by the floodwater mosquito A. atlanticus. The virus is transmitted transstadially in nature, as evidenced by our recovery of virus from larvae and males of this species. Serologic evidence, both here and elsewhere, indicates that vertebrates are infected with KEY, but their role in the transmission cycle remains unknown. We have found several animals, for example, the gray squirrel, that are potential vertebrate reservoirs for the virus. Gray squirrels possess antibodies to KEY in nature, are known to be fed upon by A. atlanticus females, and have been shown to circulate a high-titered viremia after experimental inoculation. Evidence from 1974 collections, however, indicates that A. atlanticus females ingested only a single blood meal during the period when adults were active. We will not be able to assess the relative importance of the vertebrate and mosquito cycles until much more work has been performed on vector-reservoir-virus dynamics."}
{"id": "PMID:20018", "title": "Transovarial transmission of Rickettsia-like microorganisms in mosquitoes.", "content": "The wolbachiae found in Culex pipiens and the Tafahi strain of the A. scutellaris group are small rickettsia-like symbionts of the gonads. They are extrachromosomal self-replicating units that are vertically transmitted through the ovaries. Their presence in the only two groups of mosquitoes known to exhibit incompatibility, the fact that they are found in only the Tafahi strain, and the loss of incompatibility after removal of Wolbachia in C. pipiens are compelling evidence for the role that Wolbachia plays in incompatibility.", "contents": "Transovarial transmission of Rickettsia-like microorganisms in mosquitoes. The wolbachiae found in Culex pipiens and the Tafahi strain of the A. scutellaris group are small rickettsia-like symbionts of the gonads. They are extrachromosomal self-replicating units that are vertically transmitted through the ovaries. Their presence in the only two groups of mosquitoes known to exhibit incompatibility, the fact that they are found in only the Tafahi strain, and the loss of incompatibility after removal of Wolbachia in C. pipiens are compelling evidence for the role that Wolbachia plays in incompatibility."}
{"id": "PMID:20019", "title": "[Nitrates and nitrites in plants].", "content": "The formation of aminoacids and proteins from the nitrogen which enters the roots as nitra t involves a complex reaction requiring energy. The first step requires a metalloflavoprotein, the nitrate reductase and the successive intervention of NADPH, FAD and reduced molybdenum which transfers electrons to nitrate and reduces it to nitrite. The following steps involve NADPH, FAD, Copper, Iron and Manganese, the last steps of the successive reductions being ammonia, needed for the aminoacids synthesis. The activity of the different enzymes are under the dependence of the genetic equipment of the plant, of the nitrogen and oligo-element nutrition and of the different factors acting on the photosynthesis.", "contents": "[Nitrates and nitrites in plants]. The formation of aminoacids and proteins from the nitrogen which enters the roots as nitra t involves a complex reaction requiring energy. The first step requires a metalloflavoprotein, the nitrate reductase and the successive intervention of NADPH, FAD and reduced molybdenum which transfers electrons to nitrate and reduces it to nitrite. The following steps involve NADPH, FAD, Copper, Iron and Manganese, the last steps of the successive reductions being ammonia, needed for the aminoacids synthesis. The activity of the different enzymes are under the dependence of the genetic equipment of the plant, of the nitrogen and oligo-element nutrition and of the different factors acting on the photosynthesis."}
{"id": "PMID:20020", "title": "[Formation of nitrosamines in the digestive tract].", "content": "Nitrosamines are carcinogenic compounds synthetized from amines and nitrites or nitrates, if nitrates in the reaction medium may be reduced to nitrites. Nitrosation is determined in the digestive tract of several species of laboratory animals. Two physiochemical factors appear to determine in vitro nitrosamine formation: the type of amine and the medium pH. The property of secondary amines to nitrosate is inversely related to amine basicity (checked in vivo), and it increases with the medium acidity. In vitro studies show that different types of bacteria can, even at neutral pH, catalyze nitroamine formation from their precursors. However, the role of digestive tract microbial flora in nitrosamine synthesis in the gut cannot be affirmed due to lack of in vivo studies.", "contents": "[Formation of nitrosamines in the digestive tract]. Nitrosamines are carcinogenic compounds synthetized from amines and nitrites or nitrates, if nitrates in the reaction medium may be reduced to nitrites. Nitrosation is determined in the digestive tract of several species of laboratory animals. Two physiochemical factors appear to determine in vitro nitrosamine formation: the type of amine and the medium pH. The property of secondary amines to nitrosate is inversely related to amine basicity (checked in vivo), and it increases with the medium acidity. In vitro studies show that different types of bacteria can, even at neutral pH, catalyze nitroamine formation from their precursors. However, the role of digestive tract microbial flora in nitrosamine synthesis in the gut cannot be affirmed due to lack of in vivo studies."}
{"id": "PMID:20022", "title": "[Metabolism of nitrates-nitrites].", "content": "Once the pair nitrate-nitrite--in quantity respectively set by the ingestion level or transformation level by intestinal bacteria--has entered through the intestinal mucosa, it may react with active biochemical groups. Nitrite, owing to its high oxido-reduction potential, may induce the oxidation of a large number of compounds, as for example the Fe++ heme-Fe+++ hemine system, reduced cytochromes-oxidized cytochromes system, etc. If the presence of nitrite in blood is not clearly established, this is due to the nitrite high chemical reactivity. Moreover, a transformation by the tissues of nitrates into nitrites after a nitro-reduction is quite possible.", "contents": "[Metabolism of nitrates-nitrites]. Once the pair nitrate-nitrite--in quantity respectively set by the ingestion level or transformation level by intestinal bacteria--has entered through the intestinal mucosa, it may react with active biochemical groups. Nitrite, owing to its high oxido-reduction potential, may induce the oxidation of a large number of compounds, as for example the Fe++ heme-Fe+++ hemine system, reduced cytochromes-oxidized cytochromes system, etc. If the presence of nitrite in blood is not clearly established, this is due to the nitrite high chemical reactivity. Moreover, a transformation by the tissues of nitrates into nitrites after a nitro-reduction is quite possible."}
{"id": "PMID:20023", "title": "[Effect of nitrites and nitrates on various aspects of vitamin nutritional status].", "content": "Nitrites--and sometimes nitrates--decrease the biological availability of dietary vitamins in several animal species. 1. Numerous studies show that ingested nitrites decrease the stock of liver vitamin A in nonruminants (Rat, Pig, Chicken); the effect of nitrates is less pronounced even lacking. In vitro, experiments allow to think that vitamin A and beta-carotene can be destroyed by nitrites in the diet and/or in the gastrointestinal tract. 2. Some recent works--those of Lhuissier particularly--show that nitrites can affect some vitamins of B group and their metabolism. Thiamine and vitamin B6 contents of several tissues decrease when nitrites are fed to the Rat. In the case of thiamine, the result could be partially explained by destruction of the vitamin in the diet and may be in the gastrointestinal tract. No such explanation seems to be possible in the case of vitamin B6.", "contents": "[Effect of nitrites and nitrates on various aspects of vitamin nutritional status]. Nitrites--and sometimes nitrates--decrease the biological availability of dietary vitamins in several animal species. 1. Numerous studies show that ingested nitrites decrease the stock of liver vitamin A in nonruminants (Rat, Pig, Chicken); the effect of nitrates is less pronounced even lacking. In vitro, experiments allow to think that vitamin A and beta-carotene can be destroyed by nitrites in the diet and/or in the gastrointestinal tract. 2. Some recent works--those of Lhuissier particularly--show that nitrites can affect some vitamins of B group and their metabolism. Thiamine and vitamin B6 contents of several tissues decrease when nitrites are fed to the Rat. In the case of thiamine, the result could be partially explained by destruction of the vitamin in the diet and may be in the gastrointestinal tract. No such explanation seems to be possible in the case of vitamin B6."}
{"id": "PMID:20025", "title": "pH of blood and aqueous in patients with glaucoma.", "content": "pH estimation of blood was carried out in 37 normal patients and 43 patients with chronic simple glaucoma. pH of blood did not show any statistical significant difference in the 2 groups. pH of aqueous also was noted in 8 patients with glaucoma and 8 normal patients and no significant difference was noted.", "contents": "pH of blood and aqueous in patients with glaucoma. pH estimation of blood was carried out in 37 normal patients and 43 patients with chronic simple glaucoma. pH of blood did not show any statistical significant difference in the 2 groups. pH of aqueous also was noted in 8 patients with glaucoma and 8 normal patients and no significant difference was noted."}
{"id": "PMID:20027", "title": "Bradshaw lecture, 1976. Thyroid medullary carcinoma.", "content": "The main characteristics of medullary carcinoma of the thyroid are its non-follicular histological appearance, resulting from its origin from the parafollicular C cells, its secretion of calcitonin, providing a relatively simple diagnostic test, and its equal sex incidence, in contrast to all other diseases of the thyroid. Sporadic cases are seen and it occurs in familial groups, with autosomal dominant inheritance, when it is associated with phaeochromocytoma and parathyroid hyperplasia to form the second type of multiple endocrine adenomatosis (MEA2). These last features make it necessary in every case of medullary carcinoma of the thyroid to examine other members of the family and to investigate the possibility of concomitant adrenal and parathyroid disease. The priorities of treatment when these are present and the indications for total thyroidectomy are discussed.", "contents": "Bradshaw lecture, 1976. Thyroid medullary carcinoma. The main characteristics of medullary carcinoma of the thyroid are its non-follicular histological appearance, resulting from its origin from the parafollicular C cells, its secretion of calcitonin, providing a relatively simple diagnostic test, and its equal sex incidence, in contrast to all other diseases of the thyroid. Sporadic cases are seen and it occurs in familial groups, with autosomal dominant inheritance, when it is associated with phaeochromocytoma and parathyroid hyperplasia to form the second type of multiple endocrine adenomatosis (MEA2). These last features make it necessary in every case of medullary carcinoma of the thyroid to examine other members of the family and to investigate the possibility of concomitant adrenal and parathyroid disease. The priorities of treatment when these are present and the indications for total thyroidectomy are discussed."}
{"id": "PMID:20028", "title": "Determination of serum creatinine by reaction with methyl-3,5-dinitrobenzoate in Methyl Sulfoxide.", "content": "Creatinine in serum is determined with a new reagent system consisting of methyl-3,5-dinitrobenzoate and tetramethyl ammonium hydroxide in 50% methyl sulfoxide. The method shows excellent correlation with manual and automated alkaline picrate procedures and has comparable sensitivity. The proposed method has advantages over the dinitrobenzoyl chloride assay system in terms of sensitivity, reagent stability and precision. The day-to-day coefficient of variation is 2.9-3.8%, while within day is 1.5-2.1%. The standard curve is linear beyond 20 mg/dl creatinine. Compared to the picrate method, the proposed assay is less than one half as susceptible to a combination of known interfering agents. Based on the present studies, it is recommended as an excellent alternative to the commonly used picrate procedures.", "contents": "Determination of serum creatinine by reaction with methyl-3,5-dinitrobenzoate in Methyl Sulfoxide. Creatinine in serum is determined with a new reagent system consisting of methyl-3,5-dinitrobenzoate and tetramethyl ammonium hydroxide in 50% methyl sulfoxide. The method shows excellent correlation with manual and automated alkaline picrate procedures and has comparable sensitivity. The proposed method has advantages over the dinitrobenzoyl chloride assay system in terms of sensitivity, reagent stability and precision. The day-to-day coefficient of variation is 2.9-3.8%, while within day is 1.5-2.1%. The standard curve is linear beyond 20 mg/dl creatinine. Compared to the picrate method, the proposed assay is less than one half as susceptible to a combination of known interfering agents. Based on the present studies, it is recommended as an excellent alternative to the commonly used picrate procedures."}
{"id": "PMID:20026", "title": "[Variation of the anhidrotic activities of anticholinergics with different routes of administration (author's transl)].", "content": "Anhidrotic concentrations 50 of four anticholinergics were determined in mice using an original skin palmar conductance method. Intra-peritoneal, intra-palmar and topical routes were compared. Relative anhidrotic activities according to the mode of administration of the different anticholinergics showed definite differences, e.g. hydroxyzine, which was the less active per i.p. route, was the most active per topical route. The method is likely to be a useful test for selecting the most active anticholinergic and its most efficient route of administration for the treatment of hyperhidrosis.", "contents": "[Variation of the anhidrotic activities of anticholinergics with different routes of administration (author's transl)]. Anhidrotic concentrations 50 of four anticholinergics were determined in mice using an original skin palmar conductance method. Intra-peritoneal, intra-palmar and topical routes were compared. Relative anhidrotic activities according to the mode of administration of the different anticholinergics showed definite differences, e.g. hydroxyzine, which was the less active per i.p. route, was the most active per topical route. The method is likely to be a useful test for selecting the most active anticholinergic and its most efficient route of administration for the treatment of hyperhidrosis."}
{"id": "PMID:20029", "title": "Human pancreatic alpha-amylase. II. Effects of pH, substrate and ions on the activity of the enzyme.", "content": "Purified human pancreatic alpha-amylase (alpha-1,4-glucan 4-glucano-hydrolase, EC 3.2.1.1) was found to be stable over a wide range of pH values (5.0 to 10.5) with an optimal pH for the enzymatic activity of 7.0. The Michaelis constant of the enzyme at optimal pH and assay conditions was found to be 2.51 mg per ml for soluble starch. Halide ions were required for the activity of the enzyme whereas sulfate and nitrate were not. The order of effectiveness of activation was found to be: Cl- greater than Br- greater than I- greater than F-. Calcium and magnesium were activators at concentrations of 0.001M and 0.005M, respectively, but exhibited inhibitory effects at concentrations higher than 0.005M. At 0.01M ethylenediamine tetraacetic acid (EDTA) concentration the enzymatic activity upon seven min incubation, was inhibited up to 96%. The inhibition of EDTA and calcium could be reversed upon addition of calcium and EDTA, respectively.", "contents": "Human pancreatic alpha-amylase. II. Effects of pH, substrate and ions on the activity of the enzyme. Purified human pancreatic alpha-amylase (alpha-1,4-glucan 4-glucano-hydrolase, EC 3.2.1.1) was found to be stable over a wide range of pH values (5.0 to 10.5) with an optimal pH for the enzymatic activity of 7.0. The Michaelis constant of the enzyme at optimal pH and assay conditions was found to be 2.51 mg per ml for soluble starch. Halide ions were required for the activity of the enzyme whereas sulfate and nitrate were not. The order of effectiveness of activation was found to be: Cl- greater than Br- greater than I- greater than F-. Calcium and magnesium were activators at concentrations of 0.001M and 0.005M, respectively, but exhibited inhibitory effects at concentrations higher than 0.005M. At 0.01M ethylenediamine tetraacetic acid (EDTA) concentration the enzymatic activity upon seven min incubation, was inhibited up to 96%. The inhibition of EDTA and calcium could be reversed upon addition of calcium and EDTA, respectively."}
{"id": "PMID:20030", "title": "Glucose-6-phosphate dehydrogenase in vitro correlated with in vivo activity and reticulocytosis.", "content": "In vitro activity of erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) does not always correlate with in vivo hemolytic manifestations. Many of these non-correlations are reviewed and can now be explained on the basis of altered substrate affinity and/or altered inhibition by intracellular metabolites. These alterations are not detected by standard assay conditions. The influence of a young erythrocyte population upon in vitro G-6-PD activity was determined and the lower limit of expected values shown to be raised at least to the mean of an average age erythrocyte population.", "contents": "Glucose-6-phosphate dehydrogenase in vitro correlated with in vivo activity and reticulocytosis. In vitro activity of erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) does not always correlate with in vivo hemolytic manifestations. Many of these non-correlations are reviewed and can now be explained on the basis of altered substrate affinity and/or altered inhibition by intracellular metabolites. These alterations are not detected by standard assay conditions. The influence of a young erythrocyte population upon in vitro G-6-PD activity was determined and the lower limit of expected values shown to be raised at least to the mean of an average age erythrocyte population."}
{"id": "PMID:20032", "title": "[Effects of a vagolytic substance on the circadian rhythm of the ACTH-secreting system in man].", "content": "The circadian rhythm of plasma cortisol and urinary 17-hydroxy-corticosteroids has been studied in 6 normal volunteers both in basal conditions and after the administration of a single dose of 30 mg of a banthine derivative (the beta methyl-beta-isopropylaminoethyl ester bromide of xantene-9-carbonic acid, \"Pervagal\") given orally once a day at different hours (midnight, 4 AM, 8 AM, noon, 4 PM, 8 PM). The vagolytic drug inhibits the cortisol secretion only when administered at 4 PM, 8 PM or midnight, whereas it is ineffective when given at different hours. If don't exist circadian variations of the bio-availability of the drug employed, our results suggest that also in human beings as well as in experimental animals, the cholinergic mechanisms are effective, over all if not exclusively, in starting the circadian activation of the hypothalamo-pituitary-adrenal system.", "contents": "[Effects of a vagolytic substance on the circadian rhythm of the ACTH-secreting system in man]. The circadian rhythm of plasma cortisol and urinary 17-hydroxy-corticosteroids has been studied in 6 normal volunteers both in basal conditions and after the administration of a single dose of 30 mg of a banthine derivative (the beta methyl-beta-isopropylaminoethyl ester bromide of xantene-9-carbonic acid, \"Pervagal\") given orally once a day at different hours (midnight, 4 AM, 8 AM, noon, 4 PM, 8 PM). The vagolytic drug inhibits the cortisol secretion only when administered at 4 PM, 8 PM or midnight, whereas it is ineffective when given at different hours. If don't exist circadian variations of the bio-availability of the drug employed, our results suggest that also in human beings as well as in experimental animals, the cholinergic mechanisms are effective, over all if not exclusively, in starting the circadian activation of the hypothalamo-pituitary-adrenal system."}
{"id": "PMID:20033", "title": "Chemotaxis of leucocytes: an improved method of direct microscopic observation.", "content": "Leucochemotaxis was evaluated by direct morphological observation of a cell suspension between slide and coverslip. The chemotactic index was obtained by the ratio of the number of moving leucocytes recorded within an area limited on the slide by circles traced, at the beginning and after a time period of exposure to a gradient of chemotactic factor which was placed in the center of the circle in dry state. The optimal conditions (times of exposure, pH of the medium) and the reproducibility of the assay were investigated on normal blood samples.", "contents": "Chemotaxis of leucocytes: an improved method of direct microscopic observation. Leucochemotaxis was evaluated by direct morphological observation of a cell suspension between slide and coverslip. The chemotactic index was obtained by the ratio of the number of moving leucocytes recorded within an area limited on the slide by circles traced, at the beginning and after a time period of exposure to a gradient of chemotactic factor which was placed in the center of the circle in dry state. The optimal conditions (times of exposure, pH of the medium) and the reproducibility of the assay were investigated on normal blood samples."}
{"id": "PMID:20044", "title": "Comparative stability of cephalothin and cefazolin in buffer or human serum.", "content": "A marked loss in potency was observed when cephalothin was incubated for 5 h in human serum at 37 degrees C. Cefazolin was stable under these conditions.", "contents": "Comparative stability of cephalothin and cefazolin in buffer or human serum. A marked loss in potency was observed when cephalothin was incubated for 5 h in human serum at 37 degrees C. Cefazolin was stable under these conditions."}
{"id": "PMID:20062", "title": "New health practitioners and dermatology manpower planning.", "content": "To assess the need for dermatologists in the United States, the potential role of new health practitioners in this specialty is considered. Available data on physician extenders in general and informed opinion on dermatologist extenders in particular suggest that specially trained, nonphysician personnel could substantially augment the supply of dermatological services. At present, however, widespread adoption of new staffing patterns appears unlikely. A long-run trend toward greater use of all categories of ancillary personnel in this specialty is expected, and the profession is urged to play an early and active role in this trend's development.", "contents": "New health practitioners and dermatology manpower planning. To assess the need for dermatologists in the United States, the potential role of new health practitioners in this specialty is considered. Available data on physician extenders in general and informed opinion on dermatologist extenders in particular suggest that specially trained, nonphysician personnel could substantially augment the supply of dermatological services. At present, however, widespread adoption of new staffing patterns appears unlikely. A long-run trend toward greater use of all categories of ancillary personnel in this specialty is expected, and the profession is urged to play an early and active role in this trend's development."}
{"id": "PMID:20063", "title": "The Environmental fate of three carcinogens: benzo-(alpha)-pyrene, benzidine, and vinyl chloride evaluated in laboratory model ecosystems.", "content": "Radiolabeled benzo-((alpha)-pyrene, benzidine, and vinyl chloride were evaluated in laboratory model ecosystems for environmental fate, degradation pathways, bioconcentration, and food chain accumulation. The comparative effects of microsomal detoxications were evaluated using the inhibitor piperonyl butoxide. The accumulation and bioconcentration of benzo-(alpha)-pyrene and benzidine were closely correlated with their octanol/water partition coefficients and water solubility. Benzo-(alpha)-pyrene as predicted by these parameters was bioaccumulated to substantial levels in several organisms. Vinyl chloride was not accumulated because of its high volatility.", "contents": "The Environmental fate of three carcinogens: benzo-(alpha)-pyrene, benzidine, and vinyl chloride evaluated in laboratory model ecosystems. Radiolabeled benzo-((alpha)-pyrene, benzidine, and vinyl chloride were evaluated in laboratory model ecosystems for environmental fate, degradation pathways, bioconcentration, and food chain accumulation. The comparative effects of microsomal detoxications were evaluated using the inhibitor piperonyl butoxide. The accumulation and bioconcentration of benzo-(alpha)-pyrene and benzidine were closely correlated with their octanol/water partition coefficients and water solubility. Benzo-(alpha)-pyrene as predicted by these parameters was bioaccumulated to substantial levels in several organisms. Vinyl chloride was not accumulated because of its high volatility."}
{"id": "PMID:20067", "title": "The effect of beta-adrenoceptor antagonists on the alpha-adrenoceptor blockade produced by phenoxybenzamine.", "content": "The effect of beta-adrenoceptor antagonists on the irreversible alpha-adrenoceptor blockade produced by phenoxybenzamine was studied in dogs. The pressor effects of adrenaline were revived after the inhibition by the alpha-receptor block by (+/-) propranolol, (-) INPEA, (+/-) MJ 1999 and (+/-) butoxamine. The enantiomers (+) propranolol and (+) INPEA were ineffective in this regard. (+/-) Practolol also did not revive the pressor effect of the amines. The alpha-receptor mediated effect of the amines, in the nictitating membrana-receptor blockade. It is concluded that (1) blockade of the peripheral (beta-2) receptors is essential for the revival of the pressor effects, (2) local anesthetic effect of the beta-antagonists is not involved. Further work using a series of doses of agonists and antagonists of alpha-and beta-receptors is indicated to clarify the nature of this drug-interaction.", "contents": "The effect of beta-adrenoceptor antagonists on the alpha-adrenoceptor blockade produced by phenoxybenzamine. The effect of beta-adrenoceptor antagonists on the irreversible alpha-adrenoceptor blockade produced by phenoxybenzamine was studied in dogs. The pressor effects of adrenaline were revived after the inhibition by the alpha-receptor block by (+/-) propranolol, (-) INPEA, (+/-) MJ 1999 and (+/-) butoxamine. The enantiomers (+) propranolol and (+) INPEA were ineffective in this regard. (+/-) Practolol also did not revive the pressor effect of the amines. The alpha-receptor mediated effect of the amines, in the nictitating membrana-receptor blockade. It is concluded that (1) blockade of the peripheral (beta-2) receptors is essential for the revival of the pressor effects, (2) local anesthetic effect of the beta-antagonists is not involved. Further work using a series of doses of agonists and antagonists of alpha-and beta-receptors is indicated to clarify the nature of this drug-interaction."}
{"id": "PMID:20068", "title": "[Quantitative composition of the gastrointestinal flora in the young pig].", "content": "Studies were conducted into the quantitative composition of the gastro-intestinal flora in clinically intact store pigs. The methods are described in greater detail, followed by presentation of results. In the discussion particular reference is made to literature. Conclusions are drawn regarding the topographic distribution of the various germ groups in the gastro-intestinal tract of the store pig.", "contents": "[Quantitative composition of the gastrointestinal flora in the young pig]. Studies were conducted into the quantitative composition of the gastro-intestinal flora in clinically intact store pigs. The methods are described in greater detail, followed by presentation of results. In the discussion particular reference is made to literature. Conclusions are drawn regarding the topographic distribution of the various germ groups in the gastro-intestinal tract of the store pig."}
{"id": "PMID:20069", "title": "[Alterations of cerebrospinal fluid pressure in experimental communicating hydrocephalus. Response of CSF-pressure to increased CO2-tension (author's transl)].", "content": "The response of cerebrospinal fluid pressure to increased arterial carbon dioxide tension was examined in 5 control dogs and 7 dogs with experimental communicating hydrocephalus. The cerebrospinal fluid pressure in control animals only rose to 35 mm Hg after elevation of the arterial CO2 tension. In dogs with experimental communicating hydrocephalus, however, a significant rise of intracranial pressure to 60 mm Hg can be demonstrated. This is accompained by a marked simultaneous decrease of cerebral perfusion pressure in hydrocephalic animals. Progression of communicating hydrocephalus can be explained as damage to the cerebral tissue by increased intracranial pressure waves and by ischemia due to low cerebral perfusion pressure.", "contents": "[Alterations of cerebrospinal fluid pressure in experimental communicating hydrocephalus. Response of CSF-pressure to increased CO2-tension (author's transl)]. The response of cerebrospinal fluid pressure to increased arterial carbon dioxide tension was examined in 5 control dogs and 7 dogs with experimental communicating hydrocephalus. The cerebrospinal fluid pressure in control animals only rose to 35 mm Hg after elevation of the arterial CO2 tension. In dogs with experimental communicating hydrocephalus, however, a significant rise of intracranial pressure to 60 mm Hg can be demonstrated. This is accompained by a marked simultaneous decrease of cerebral perfusion pressure in hydrocephalic animals. Progression of communicating hydrocephalus can be explained as damage to the cerebral tissue by increased intracranial pressure waves and by ischemia due to low cerebral perfusion pressure."}
{"id": "PMID:20070", "title": "[Clinical trial with a new anti-epileptic: barbexaclone].", "content": "A new anti-epileptic agent (barbexaclone) was tried in 48 patients suffering from epilepsy and presenting a total of 67 types of crises. All the patients were considered \"bad cases\" because either by the intensity of the epileptic manifestations or by their refractoriness to the usual medications. The results, similar to others already published, could be considered as good for grand mal epilepsy both for those convulsions occurring during either the sleeping or waking hours and suggest further observations in focal crises. Though not considered as a first line medication in petit mal seizuras the drug gave excellent results when used as an adjuvant in the supression of absences and the annulation of convulsant effects of some drugs used in petit mal. No toxic reactions were noted, and the side effects, which were never very intense, tended to disappear in the majority of cases with continued use of the drug.", "contents": "[Clinical trial with a new anti-epileptic: barbexaclone]. A new anti-epileptic agent (barbexaclone) was tried in 48 patients suffering from epilepsy and presenting a total of 67 types of crises. All the patients were considered \"bad cases\" because either by the intensity of the epileptic manifestations or by their refractoriness to the usual medications. The results, similar to others already published, could be considered as good for grand mal epilepsy both for those convulsions occurring during either the sleeping or waking hours and suggest further observations in focal crises. Though not considered as a first line medication in petit mal seizuras the drug gave excellent results when used as an adjuvant in the supression of absences and the annulation of convulsant effects of some drugs used in petit mal. No toxic reactions were noted, and the side effects, which were never very intense, tended to disappear in the majority of cases with continued use of the drug."}
{"id": "PMID:20072", "title": "Generalized glycogenosis in beef shorthorn cattle--heterozygote detection.", "content": "A preliminary study of acidic alpha-glucosidase in a variety of tissues was carried out in an attempt to develop a test which might be used to detect individuals heterozygous for the genetype associated with generalized glycogenosis in beef Shorthorn cattle. Of the tissues readily available peripheral lymphocytes were chosen as being likely to be the most suitable. It was concluded that, when coupled with genealogical information, assays of alpha-glucosidase in extracts of lymphocytes were useful for identifying heterozygous individuals with a reasonably high degree of probability.", "contents": "Generalized glycogenosis in beef shorthorn cattle--heterozygote detection. A preliminary study of acidic alpha-glucosidase in a variety of tissues was carried out in an attempt to develop a test which might be used to detect individuals heterozygous for the genetype associated with generalized glycogenosis in beef Shorthorn cattle. Of the tissues readily available peripheral lymphocytes were chosen as being likely to be the most suitable. It was concluded that, when coupled with genealogical information, assays of alpha-glucosidase in extracts of lymphocytes were useful for identifying heterozygous individuals with a reasonably high degree of probability."}
{"id": "PMID:20077", "title": "4,4'-dimethylcholesta-7,9,14-trienol is an intermediate in the demethylation of dihydroagnosterol.", "content": "1. 4,4'-Dimethylcholesta-7,9,14-trienol is an intermediate in the metabolism of dihydroagnosterol to cholesterol by rat liver homogenate. 2. This triene is reduced by a rat liver microsomal preparation in the presence of NADPH to give 4,4'-dimethylcholesta-7,9-dienol under anaerobic conditions. 3. Reduction of the triene in the presence of [4-3H2]NADPH resulted in the incorporation of 3H into the product. 4. Under aerobic conditions the triene is converted into cholesterol by a rat liver homogenate.", "contents": "4,4'-dimethylcholesta-7,9,14-trienol is an intermediate in the demethylation of dihydroagnosterol. 1. 4,4'-Dimethylcholesta-7,9,14-trienol is an intermediate in the metabolism of dihydroagnosterol to cholesterol by rat liver homogenate. 2. This triene is reduced by a rat liver microsomal preparation in the presence of NADPH to give 4,4'-dimethylcholesta-7,9-dienol under anaerobic conditions. 3. Reduction of the triene in the presence of [4-3H2]NADPH resulted in the incorporation of 3H into the product. 4. Under aerobic conditions the triene is converted into cholesterol by a rat liver homogenate."}
{"id": "PMID:20112", "title": "[In vitro studies on parsalmide / bioavailability and protein binding (author's transl)].", "content": "The values of the diffusion constants at the different pH-values obtained using Stricker's apparatus, demonstrate that 2-propargyloxy-5-amino-N-(n-butyl)-benzamide(parsalmide, My 46-1) is characterized by a good absorption rate at gastric level and by a high absorption rate in the intestinal tract. The per cent of parsalmide bound to serum proteins, mainly to serum albumin, decreases with increasing concentration of parsalmide. Human serum binds about 55--70%, whereas bovine and equine serum bind about 40--60% of parsalmide at the different concentrations tested. The binding between parsalmide and serum proteins is a weak one: bound parsalmide is therefore set free very easily.", "contents": "[In vitro studies on parsalmide / bioavailability and protein binding (author's transl)]. The values of the diffusion constants at the different pH-values obtained using Stricker's apparatus, demonstrate that 2-propargyloxy-5-amino-N-(n-butyl)-benzamide(parsalmide, My 46-1) is characterized by a good absorption rate at gastric level and by a high absorption rate in the intestinal tract. The per cent of parsalmide bound to serum proteins, mainly to serum albumin, decreases with increasing concentration of parsalmide. Human serum binds about 55--70%, whereas bovine and equine serum bind about 40--60% of parsalmide at the different concentrations tested. The binding between parsalmide and serum proteins is a weak one: bound parsalmide is therefore set free very easily."}
{"id": "PMID:20114", "title": "Bufuralol, a new beta-adrenoceptor blocking agent in a series of benzofuran-2-ethanolamines. Part 2: pharmacology.", "content": "1-(7-Ethylbenzofuran-2-yl)-2-tert.-butylamino-1-hydroxyethane hydrochloride (bufuralol) is a non-selective beta-adrenoceptor blocking agent which closely resembles propranolol in its properties, including potency. Bufuralol is devoid of alpha-adrenoceptor blocking activity but possesses beta-adrenoceptor agonist activity. beta-Adrenoceptor blocking activity resides mainly in the (-)-isomer though membrane stabilising properties are associated with both optical isomers.", "contents": "Bufuralol, a new beta-adrenoceptor blocking agent in a series of benzofuran-2-ethanolamines. Part 2: pharmacology. 1-(7-Ethylbenzofuran-2-yl)-2-tert.-butylamino-1-hydroxyethane hydrochloride (bufuralol) is a non-selective beta-adrenoceptor blocking agent which closely resembles propranolol in its properties, including potency. Bufuralol is devoid of alpha-adrenoceptor blocking activity but possesses beta-adrenoceptor agonist activity. beta-Adrenoceptor blocking activity resides mainly in the (-)-isomer though membrane stabilising properties are associated with both optical isomers."}
{"id": "PMID:20111", "title": "Local and systemic reactions to puncture injuries by the sea urchin spine and the date palm thorn.", "content": "Puncture wounds were cuased in 9 patients by sea urchin spines and 1 patient by a date palm thorn. All 10 patients developed local inflammatory reactions, which were moderate to severe in 7. Two patients exhibited severe systemic illnesses, and a marked synovitis was present in 2 others. Several of the patients presented as difficult diagnostic problems with signs and symptoms suggestive of an arthritic disease. Six required surgical removal of the foreign body.", "contents": "Local and systemic reactions to puncture injuries by the sea urchin spine and the date palm thorn. Puncture wounds were cuased in 9 patients by sea urchin spines and 1 patient by a date palm thorn. All 10 patients developed local inflammatory reactions, which were moderate to severe in 7. Two patients exhibited severe systemic illnesses, and a marked synovitis was present in 2 others. Several of the patients presented as difficult diagnostic problems with signs and symptoms suggestive of an arthritic disease. Six required surgical removal of the foreign body."}
{"id": "PMID:20116", "title": "Amiodarone-like haemodynamic and non-competitive antiadrenergic properties of a benzoyl-indolizine.", "content": "1. 2-Ethyl-3-(4-gamma-di-n-butylaminopropoxy-benzoyl)-indolizine hydrochloride (L 9394) induced in the ananesthetized dog a marked and long-lasting decrease in heart rate together with a transient reduction in blood pressure. 2. L 9394 decreased Robinson's index, an effect which suggests that the substance reduces the oxygen requirements of the heart. 3. L 9394 markedly increased coronary arterial blood flow. 4. L 9394 is endowed with non-competitive antiadrenergic properties. 5. L 9394 did not impair cardiac function since cardiac output and stroke volume increased appreciably during the initial phase of action and did not fall below the control values at any time thereafter. 6. The overall haemodynamic properties of L 9394, which were similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris.", "contents": "Amiodarone-like haemodynamic and non-competitive antiadrenergic properties of a benzoyl-indolizine. 1. 2-Ethyl-3-(4-gamma-di-n-butylaminopropoxy-benzoyl)-indolizine hydrochloride (L 9394) induced in the ananesthetized dog a marked and long-lasting decrease in heart rate together with a transient reduction in blood pressure. 2. L 9394 decreased Robinson's index, an effect which suggests that the substance reduces the oxygen requirements of the heart. 3. L 9394 markedly increased coronary arterial blood flow. 4. L 9394 is endowed with non-competitive antiadrenergic properties. 5. L 9394 did not impair cardiac function since cardiac output and stroke volume increased appreciably during the initial phase of action and did not fall below the control values at any time thereafter. 6. The overall haemodynamic properties of L 9394, which were similar to those of amiodarone, are considered to be potentially valuable for the long-term treatment of angina pectoris."}
{"id": "PMID:20124", "title": "The effect of mental arithmetic in normotensive and hypertensive subjects, and its modification by beta-adrenergic receptor blockade.", "content": "1 The effects of a 5-min period of sustained mental arithmetic upon blood pressure and heart rate were determined in several groups of healthy subjects and hypertensive patients. 2 The arithmetic produced significant increases in heart rate and blood pressure (both systolic and diastolic) in both normotensive and hypertensive subjects. 3 The blood pressure changes were neither attenuated nor enhanced by the prior administration of basis. 4 In subjects habituated to the test the heart rate increase was unaffected by the drugs, but in those less familiar with the test it was usually attenuated. 5 Although the beta1-adrenoceptor selective blocker, metoprolol, caused decreases in baseline values for blood pressure and heart rate similar to those observed with the use of the two non-selective blockrs, it was shown in a double-blind crossover comparison with propranolol that the haemodynamic changes provoked by the mental arithmetic were not less in the presence of beta1-receptor blockade than when both beta1- and beta2-receptors were blocked. 6 These findings suggest that, during beta2-adrenoceptor blockade, the haemodynamic effects of minor mental stress are not exaggerated because of uncompensated alpha-receptor mediated vasoconstriction, such as occurs following adrenaline infusion.", "contents": "The effect of mental arithmetic in normotensive and hypertensive subjects, and its modification by beta-adrenergic receptor blockade. 1 The effects of a 5-min period of sustained mental arithmetic upon blood pressure and heart rate were determined in several groups of healthy subjects and hypertensive patients. 2 The arithmetic produced significant increases in heart rate and blood pressure (both systolic and diastolic) in both normotensive and hypertensive subjects. 3 The blood pressure changes were neither attenuated nor enhanced by the prior administration of basis. 4 In subjects habituated to the test the heart rate increase was unaffected by the drugs, but in those less familiar with the test it was usually attenuated. 5 Although the beta1-adrenoceptor selective blocker, metoprolol, caused decreases in baseline values for blood pressure and heart rate similar to those observed with the use of the two non-selective blockrs, it was shown in a double-blind crossover comparison with propranolol that the haemodynamic changes provoked by the mental arithmetic were not less in the presence of beta1-receptor blockade than when both beta1- and beta2-receptors were blocked. 6 These findings suggest that, during beta2-adrenoceptor blockade, the haemodynamic effects of minor mental stress are not exaggerated because of uncompensated alpha-receptor mediated vasoconstriction, such as occurs following adrenaline infusion."}
{"id": "PMID:20126", "title": "Rupture of base pairing in double-stranded poly(riboadenylic acid)-poly(ribouridylic acid) by formaldehyde: medium chain lenghts.", "content": "By assuming that the opening of hydrogen bonds due to thermal fluctuations is a very fast step and that the reaction of formaldehyde with the imino or amino group is a slow step, we have constructed a model for the unwinding process of poly(A-U) induced by formaldehyde. The denaturation equation derived from the model is essentially the same as that of the zipper model for moderately long chain lengths. The model predicts the following phenomena which are in agreement with our experimental findings. The rate of unwinding is approximately first order for unfractionated polynucleotides and zero order for fractionated samples. This means that formaldehyde ruptures helical residues sequentially starting from the ends and working toward the center. Our model further predicts that the denaturation rate is linearly dependent on -log[Na+] and pH at low ionic strength and is almost independent of [Na+] and pH at high ionic strength. Spectrophotometric measurements on poly(A-U) were done to confirm our theoretical findings.", "contents": "Rupture of base pairing in double-stranded poly(riboadenylic acid)-poly(ribouridylic acid) by formaldehyde: medium chain lenghts. By assuming that the opening of hydrogen bonds due to thermal fluctuations is a very fast step and that the reaction of formaldehyde with the imino or amino group is a slow step, we have constructed a model for the unwinding process of poly(A-U) induced by formaldehyde. The denaturation equation derived from the model is essentially the same as that of the zipper model for moderately long chain lengths. The model predicts the following phenomena which are in agreement with our experimental findings. The rate of unwinding is approximately first order for unfractionated polynucleotides and zero order for fractionated samples. This means that formaldehyde ruptures helical residues sequentially starting from the ends and working toward the center. Our model further predicts that the denaturation rate is linearly dependent on -log[Na+] and pH at low ionic strength and is almost independent of [Na+] and pH at high ionic strength. Spectrophotometric measurements on poly(A-U) were done to confirm our theoretical findings."}
{"id": "PMID:20127", "title": "Magnetic resonance investigation of ionizable residues at the active site of thermolysin.", "content": "The details of the pH dependence of the thermodynamic and magnetic interactions of the active-site region of thermolysin in which manganese has replaced the active-site zinc atom and the inhibitor N-trifluoroacetyl-D-phenylalanine have been examined. These show a number of ionizable groups in the active-site region. A cooperative displacement of manganese at the catalytic site is observed as pH is lowered. This appears to be the result of the protonation of histidine-142 and -146 which act as metal ligands. The metal is 50% displaced at pH 6.0. At higher pH values, the environment of the bound manganese changes as a result of the ionization of at least two groups of approximate pKa = 8.5 and 9.5. These values are assigned to tyrosine-157 and to the water molecule which acts as a metal ligand at the active site. The binding behavior of the inhibitor strongly suggests that two molecules of inhibitor bind to the enzyme. The weaker site is competitive with the synthetic substrate FAGLA (furylacryloylglycyl-leucinamide), while the strong site has no effect on FAGLA hydrolysis. This second site is in the vicinity of the active site with a distance of 8 A or less between the trifluoromethyl group and manganese bound at the active site.", "contents": "Magnetic resonance investigation of ionizable residues at the active site of thermolysin. The details of the pH dependence of the thermodynamic and magnetic interactions of the active-site region of thermolysin in which manganese has replaced the active-site zinc atom and the inhibitor N-trifluoroacetyl-D-phenylalanine have been examined. These show a number of ionizable groups in the active-site region. A cooperative displacement of manganese at the catalytic site is observed as pH is lowered. This appears to be the result of the protonation of histidine-142 and -146 which act as metal ligands. The metal is 50% displaced at pH 6.0. At higher pH values, the environment of the bound manganese changes as a result of the ionization of at least two groups of approximate pKa = 8.5 and 9.5. These values are assigned to tyrosine-157 and to the water molecule which acts as a metal ligand at the active site. The binding behavior of the inhibitor strongly suggests that two molecules of inhibitor bind to the enzyme. The weaker site is competitive with the synthetic substrate FAGLA (furylacryloylglycyl-leucinamide), while the strong site has no effect on FAGLA hydrolysis. This second site is in the vicinity of the active site with a distance of 8 A or less between the trifluoromethyl group and manganese bound at the active site."}
{"id": "PMID:20134", "title": "Studies on the reactive properties of histone amino groups: reactivities of free histones and histones in chromatin as a function of ionic strength.", "content": "The reactivity of the amino groups of the five histones towards acetic anhydride has been measured and with the exception of histone IIb2 the reactivities are very similar to those of exposed lysines with an average pK of 9.5. In addition the reactivities of these groups from 0.20 to 1.0 M NaCl and the reactivity of a peptide containing lysines 5, 8, 12 and 16 of histone IV have been measured in chromatin. It is concluded that at the lower ionic strengths the large proportion of the amino groups are buried for both the histones and the region of histone IV studied. Data obtained from the measurement of the reactivity of standard proline compounds and from a pH and ionic strength study indicate that the N-terminal proline of histone IIb2 is exposed.", "contents": "Studies on the reactive properties of histone amino groups: reactivities of free histones and histones in chromatin as a function of ionic strength. The reactivity of the amino groups of the five histones towards acetic anhydride has been measured and with the exception of histone IIb2 the reactivities are very similar to those of exposed lysines with an average pK of 9.5. In addition the reactivities of these groups from 0.20 to 1.0 M NaCl and the reactivity of a peptide containing lysines 5, 8, 12 and 16 of histone IV have been measured in chromatin. It is concluded that at the lower ionic strengths the large proportion of the amino groups are buried for both the histones and the region of histone IV studied. Data obtained from the measurement of the reactivity of standard proline compounds and from a pH and ionic strength study indicate that the N-terminal proline of histone IIb2 is exposed."}
{"id": "PMID:20136", "title": "pH-dependent changes in proton:substrate stoichiometries during active transport in Escherichia coli membrane vesicles.", "content": "Experiments are presented in which the proton electrochemical gradient (deltamuH+) IN Escherichia coli membrane vesicles (interior negative and alkaline) was measured under a variety of conditions and compared with steady-state levels of accumulation of lactose, proline, D-lactate, and glucose-6-P measured under identical conditions. Accumulation of lactose and proline is proportional to the magnitude of deltamuH+ at pH 5.5, where the pH gradient (deltapH) and the electrical potential (deltapsi) both contribute to deltamuH+, and at pH 7.5, where deltapsi represents the only component of deltamuH+. Moreover, the proportionality constants between deltamuH+ and lactose or proline accumulation indicate that the proton:substrate stoichiometries are 1:1 at pH 5.5 and 2:1 at pH 7.5. Evidence is also presented which indicates that the functional group responsible for the increase in proton:proline stoichiometry has a pK of approximately 6.8. Accumulation of D-lactate and glucose-6-P is directly related to the magnitude of deltapH at pH 5.5, and stoichiometry values of one and approximately 1.7 are obtained for D-lactate and glucose-6-P, respectively, at this pH. At pH 7.5, on the other hand, accumulation of each organic acid bears a linear relationship to deltapsi, and proton:substrate stoichiometries of unity are observed in both instances. The results are consistent with the models discussed by Rottenberg (Rottenberg, H. (1976), FEBS Lett. 66, 159).", "contents": "pH-dependent changes in proton:substrate stoichiometries during active transport in Escherichia coli membrane vesicles. Experiments are presented in which the proton electrochemical gradient (deltamuH+) IN Escherichia coli membrane vesicles (interior negative and alkaline) was measured under a variety of conditions and compared with steady-state levels of accumulation of lactose, proline, D-lactate, and glucose-6-P measured under identical conditions. Accumulation of lactose and proline is proportional to the magnitude of deltamuH+ at pH 5.5, where the pH gradient (deltapH) and the electrical potential (deltapsi) both contribute to deltamuH+, and at pH 7.5, where deltapsi represents the only component of deltamuH+. Moreover, the proportionality constants between deltamuH+ and lactose or proline accumulation indicate that the proton:substrate stoichiometries are 1:1 at pH 5.5 and 2:1 at pH 7.5. Evidence is also presented which indicates that the functional group responsible for the increase in proton:proline stoichiometry has a pK of approximately 6.8. Accumulation of D-lactate and glucose-6-P is directly related to the magnitude of deltapH at pH 5.5, and stoichiometry values of one and approximately 1.7 are obtained for D-lactate and glucose-6-P, respectively, at this pH. At pH 7.5, on the other hand, accumulation of each organic acid bears a linear relationship to deltapsi, and proton:substrate stoichiometries of unity are observed in both instances. The results are consistent with the models discussed by Rottenberg (Rottenberg, H. (1976), FEBS Lett. 66, 159)."}
{"id": "PMID:20141", "title": "Weak acid accumulation in the serosal extracellular compartment of the frog gastric mucosa.", "content": "The dimethyloxazolidine dione distribution in the extracellular compartments of the frog gastric mucosa was analyzed by washout kinetics. The volumes of the two extracellular compartments, serosal and mucosal, were estimated by inulin washout as 0.435 +/- 0.019 and 0.176 +/- 0.018 microliter/microliter tissue water, respectively. In the serosal extracellular space, significant dimethyloxazolidine dione accumulations of 2.63 +/- 0.25, 2.28 +/- 0.16, and 1.86 +/- 0.08 times that of the bathing media were found for bathing solutions with pH values of 6.9, 7.4, and 7.9 respectively. A high pH of the serosal extracellular fluid by itself could not account for the high values of dimethyloxazolidine dione accumulation. A difference in the total dimethyloxazolidine dione accumulation requires: (a) the existence of differences in the pH values and also the existence of a difference in the diffusion coefficient of the two forms of dimethyloxazolidine dione; or (b), a binding of one of the two forms, i.e., binding of dimethyloxazolidine dione form by fixed charges.", "contents": "Weak acid accumulation in the serosal extracellular compartment of the frog gastric mucosa. The dimethyloxazolidine dione distribution in the extracellular compartments of the frog gastric mucosa was analyzed by washout kinetics. The volumes of the two extracellular compartments, serosal and mucosal, were estimated by inulin washout as 0.435 +/- 0.019 and 0.176 +/- 0.018 microliter/microliter tissue water, respectively. In the serosal extracellular space, significant dimethyloxazolidine dione accumulations of 2.63 +/- 0.25, 2.28 +/- 0.16, and 1.86 +/- 0.08 times that of the bathing media were found for bathing solutions with pH values of 6.9, 7.4, and 7.9 respectively. A high pH of the serosal extracellular fluid by itself could not account for the high values of dimethyloxazolidine dione accumulation. A difference in the total dimethyloxazolidine dione accumulation requires: (a) the existence of differences in the pH values and also the existence of a difference in the diffusion coefficient of the two forms of dimethyloxazolidine dione; or (b), a binding of one of the two forms, i.e., binding of dimethyloxazolidine dione form by fixed charges."}
{"id": "PMID:20142", "title": "Intracellular pH and the kinetics of Rb+ uptake by yeast non-carrier versus mobile carrier-mediated uptake.", "content": "The effect of changes in the intracellular pH upon the concentration dependence of the Rb+ uptake by yeast is investigated. It is shown, that the uptake of Rb+ can be described by a mechanism in which the total concentration of primary binding sites at the outer side of the membrane is independent of the intracellular ligand composition and of the membrane potential, and the influx rate constants depend upon the intracellular pH and/or upon the membrane potential. It is argued that the involvement of a mobile carrier mechanism is not likely.", "contents": "Intracellular pH and the kinetics of Rb+ uptake by yeast non-carrier versus mobile carrier-mediated uptake. The effect of changes in the intracellular pH upon the concentration dependence of the Rb+ uptake by yeast is investigated. It is shown, that the uptake of Rb+ can be described by a mechanism in which the total concentration of primary binding sites at the outer side of the membrane is independent of the intracellular ligand composition and of the membrane potential, and the influx rate constants depend upon the intracellular pH and/or upon the membrane potential. It is argued that the involvement of a mobile carrier mechanism is not likely."}
{"id": "PMID:20143", "title": "Active transport of L-sorbose and 2-deoxy-D-galactose in Saccharomyces fragilis.", "content": "Sorbose and 2-deoxy-D-galactose are taken up in Saccharomyces fragilis by an active transport mechanism, as indicated by the energy requirement of the process and the accumulation of free sugar against the concentration gradient. There are no indications for transport-associated phosphorylation as mechanism of energy coupling with these two sugars. The measured sugar-proton cotransport and the influx inhibition by uncouplers suggest a chemiosmotic coupling mechanism. Thus there are at least two different active transport mechanisms operative in Saccharomyces fragilis: transport-associated phosphorylation in the case of 2-deoxy-D-glucose and chemiosmotic coupling in the case of sorbose and 2-deoxy-D-galactose. The differences between the two mechanisms are discussed. Uncouplers do not stimulate downhill sorbose transport in energy-depleted cells and evoke an almost complete inhibition of efflux and of exchange transport. The differences between this sugar-proton cotransport system and similar systems in bacteria and Chlorella are discussed.", "contents": "Active transport of L-sorbose and 2-deoxy-D-galactose in Saccharomyces fragilis. Sorbose and 2-deoxy-D-galactose are taken up in Saccharomyces fragilis by an active transport mechanism, as indicated by the energy requirement of the process and the accumulation of free sugar against the concentration gradient. There are no indications for transport-associated phosphorylation as mechanism of energy coupling with these two sugars. The measured sugar-proton cotransport and the influx inhibition by uncouplers suggest a chemiosmotic coupling mechanism. Thus there are at least two different active transport mechanisms operative in Saccharomyces fragilis: transport-associated phosphorylation in the case of 2-deoxy-D-glucose and chemiosmotic coupling in the case of sorbose and 2-deoxy-D-galactose. The differences between the two mechanisms are discussed. Uncouplers do not stimulate downhill sorbose transport in energy-depleted cells and evoke an almost complete inhibition of efflux and of exchange transport. The differences between this sugar-proton cotransport system and similar systems in bacteria and Chlorella are discussed."}
{"id": "PMID:20144", "title": "Phase transition in charged lipid membranes.", "content": "Experimental results on the effect of electrostatics on bilayer phase transitions are compared with corresponding data for monolayers and the predictions of electrical double layer theory. The two substantial conclusions which emerge are that: (i) double layer theory based on a continuous surface charge distribution cannot explain all the relevant data, a situation which may be improved by taking into account the discrete nature of the surface charge distribution; (ii) the crystal - liquid crystal phase transition of charged bilayer membranes is always a continuous one which takes place through an intermediate state consisting of both fluid and frozen domains.", "contents": "Phase transition in charged lipid membranes. Experimental results on the effect of electrostatics on bilayer phase transitions are compared with corresponding data for monolayers and the predictions of electrical double layer theory. The two substantial conclusions which emerge are that: (i) double layer theory based on a continuous surface charge distribution cannot explain all the relevant data, a situation which may be improved by taking into account the discrete nature of the surface charge distribution; (ii) the crystal - liquid crystal phase transition of charged bilayer membranes is always a continuous one which takes place through an intermediate state consisting of both fluid and frozen domains."}
{"id": "PMID:20145", "title": "Interaction of phosphate with monovalent cation uptake in yeast.", "content": "The uptake of monovalent cations by yeast via the monovalent cation uptake mechanism is inhibited by phosphate. The inhibition of Rb+ uptake shows saturation kinetics and the phosphate concentration at which half-maximal inhibition is observed is equal to the Km of phosphate for the sodium-independent phosphate uptake mechanism. The kinetic coefficients of Rb+ and TI+ uptake are affected by phosphate: the maximal rate of uptake is decreased and the apparent affinity constants for the translocation sites are increased. In the case of Na+ uptake, the inhibition by phosphate may be partly or completely compensated by stimulation of Na+ uptake via a sodium-phosphate cotransport mechanism. Phosphate effects a transient stimulation of the efflux of the lipophilic cation dibenzyldimethylammonium from preloaded yeast cells and a transient inhibition of dibenzyldimethylammonium uptake. Possibly, the inhibition of monovalent cation uptake in yeast can be explained by a transient depolarization of the cell membrane by phosphate.", "contents": "Interaction of phosphate with monovalent cation uptake in yeast. The uptake of monovalent cations by yeast via the monovalent cation uptake mechanism is inhibited by phosphate. The inhibition of Rb+ uptake shows saturation kinetics and the phosphate concentration at which half-maximal inhibition is observed is equal to the Km of phosphate for the sodium-independent phosphate uptake mechanism. The kinetic coefficients of Rb+ and TI+ uptake are affected by phosphate: the maximal rate of uptake is decreased and the apparent affinity constants for the translocation sites are increased. In the case of Na+ uptake, the inhibition by phosphate may be partly or completely compensated by stimulation of Na+ uptake via a sodium-phosphate cotransport mechanism. Phosphate effects a transient stimulation of the efflux of the lipophilic cation dibenzyldimethylammonium from preloaded yeast cells and a transient inhibition of dibenzyldimethylammonium uptake. Possibly, the inhibition of monovalent cation uptake in yeast can be explained by a transient depolarization of the cell membrane by phosphate."}
{"id": "PMID:20146", "title": "Endonuclease activity in nuclei of Physarum polycephalum. Partial purification and characterization.", "content": "An endonuclease, present in the microplasmodia of Physarum polycephalum, has been partially purified from isolated nuclei by DEAE-cellulose and Sephadex G-75 chromatography. 1. The endonuclease produced single-strand scissions in double-stranded DNA which resulted in the generation of 5'-phosphoryl and 3'-hydroxyl termini. No activity was observed with single-stranded DNA as substrate. 2. The pH optimum was approximately 8.5. 3. Divalent cations were essential for enzyme activity. MnCl2 and MgCl2 gave maximal activity. CaCl2, ZnCl2 or CoCl2 did not activate the enzyme. 4. The endonuclease activity was highly sensitive to monovalent cations. 5. Endonuclease activity was found in two forms after gel filtration: an activity in a homogeneous peak with a molecular weight of approx. 20 000, and an activity that had a heterogeneous molecular weight and which was isolated in a complex with DNA. A possible function of the endonuclease in DNA replication is discussed.", "contents": "Endonuclease activity in nuclei of Physarum polycephalum. Partial purification and characterization. An endonuclease, present in the microplasmodia of Physarum polycephalum, has been partially purified from isolated nuclei by DEAE-cellulose and Sephadex G-75 chromatography. 1. The endonuclease produced single-strand scissions in double-stranded DNA which resulted in the generation of 5'-phosphoryl and 3'-hydroxyl termini. No activity was observed with single-stranded DNA as substrate. 2. The pH optimum was approximately 8.5. 3. Divalent cations were essential for enzyme activity. MnCl2 and MgCl2 gave maximal activity. CaCl2, ZnCl2 or CoCl2 did not activate the enzyme. 4. The endonuclease activity was highly sensitive to monovalent cations. 5. Endonuclease activity was found in two forms after gel filtration: an activity in a homogeneous peak with a molecular weight of approx. 20 000, and an activity that had a heterogeneous molecular weight and which was isolated in a complex with DNA. A possible function of the endonuclease in DNA replication is discussed."}
{"id": "PMID:20147", "title": "Purification, crystallization and properties of triacylglycerol lipase from Pseudomonas fluorescens.", "content": "Triacylglycerol lipase of Pseudomonas fluorescens was purified from the crude enzyme by ammonium sulfate precipitation and chromatographies on Sephadex G-75 and DEAE-cellulose. The crystallization of the lipase was successfully carried out. The purified lipase was demonstrated to be homogenous on disc electrophoresis and its molecular weight was calculated to be 32 000 by gel filtration. The optimum pH for hydrolysis of sesame oil was 7.0. The enzyme was stable up to 40 degrees C under the condition of pH 7.0 for 30 min and had more than 80% of the remaining activity between pH 5.0--11.0 at 37 degrees C for 60 min. The lipase was strongly inhibited by iodine and partially inhibited by FeCl3 and N-bromosuccinimide, and showed the most activity on tricaproyglycerol, among the triacylglycerols used.", "contents": "Purification, crystallization and properties of triacylglycerol lipase from Pseudomonas fluorescens. Triacylglycerol lipase of Pseudomonas fluorescens was purified from the crude enzyme by ammonium sulfate precipitation and chromatographies on Sephadex G-75 and DEAE-cellulose. The crystallization of the lipase was successfully carried out. The purified lipase was demonstrated to be homogenous on disc electrophoresis and its molecular weight was calculated to be 32 000 by gel filtration. The optimum pH for hydrolysis of sesame oil was 7.0. The enzyme was stable up to 40 degrees C under the condition of pH 7.0 for 30 min and had more than 80% of the remaining activity between pH 5.0--11.0 at 37 degrees C for 60 min. The lipase was strongly inhibited by iodine and partially inhibited by FeCl3 and N-bromosuccinimide, and showed the most activity on tricaproyglycerol, among the triacylglycerols used."}
{"id": "PMID:20148", "title": "Two cholesterol ester hydrolases. Distribution in rat tissues and in cultured human fibroblasts and monkey arterial smooth muscle cells.", "content": "Hydrolytic activity against acetone-dispersed [4-14C]cholesterol oleate has been assayed as a function of pH in seven parenchymal tissues, blood cells, and plasma of the rat, as well as in cultured human fibroblasts and monkey (Macaca nemestrina) arterial smooth muscle cells. Both acid and neutral hydrolytic activities were present in all of these except rat plasma. The pH optima were in all cases close to pH 4.5 and pH 6.8. Acid activity was quite constant from tissue to tissue, while neutral activity varied greatly, being greatest in adrenal, testis, and adipose tissue. Subcellular fractionation of human fibroblasts allowed demonstration that activities at pH 4.5 and pH 6.8 were concentrated in different fractions, apparently lysosomal and polysomal, respectively. It appears most cell types, including fibroblasts and smooth muscle cells, contain two separate enzymes capable of hydrolyzing cholesterol esters. The neutral pH polysomal enzyme, which is especially prominent in certain tissues, may have a function related to the specialized roles of these tissues.", "contents": "Two cholesterol ester hydrolases. Distribution in rat tissues and in cultured human fibroblasts and monkey arterial smooth muscle cells. Hydrolytic activity against acetone-dispersed [4-14C]cholesterol oleate has been assayed as a function of pH in seven parenchymal tissues, blood cells, and plasma of the rat, as well as in cultured human fibroblasts and monkey (Macaca nemestrina) arterial smooth muscle cells. Both acid and neutral hydrolytic activities were present in all of these except rat plasma. The pH optima were in all cases close to pH 4.5 and pH 6.8. Acid activity was quite constant from tissue to tissue, while neutral activity varied greatly, being greatest in adrenal, testis, and adipose tissue. Subcellular fractionation of human fibroblasts allowed demonstration that activities at pH 4.5 and pH 6.8 were concentrated in different fractions, apparently lysosomal and polysomal, respectively. It appears most cell types, including fibroblasts and smooth muscle cells, contain two separate enzymes capable of hydrolyzing cholesterol esters. The neutral pH polysomal enzyme, which is especially prominent in certain tissues, may have a function related to the specialized roles of these tissues."}
{"id": "PMID:20149", "title": "Studies on Tetrahymena membranes. Palmitoyl-coenzyme a desaturase, a possible key enzyme for temperature adaptation in Tetrahymena microsomes.", "content": "(1) Microsomes from a thermotolerant Tetrahymena NT-1 catalyze the conversion of palmitoyl-CoA to palmitoleate. (2) Palmitoyl-CoA desaturase enzyme requires molecular oxygen and NADH or NADPH as cofactor and its activity is inhibited by cyanide. A pH optimum range 7.0--7.3 is observed. (3) There is a clear break at 30 degrees C and a slight bend around 15 degrees C in the Arrhenius plots of palmitoyl-CoA desaturase activity. (4) After quenching from 39.5 degrees C, at 26 degrees C microsomal membranes show small particle-free areas, when examined by freeze-fracture electron microscopy, indicating the onset of phase separation. Larger smooth areas devoid of membrane-intercalated particles are observed in microsomes at 23 and 15 degrees C. The results support evidence that the thermally induced transition of desaturase enzyme activity in related to the altered membrane properties due to temperature change.", "contents": "Studies on Tetrahymena membranes. Palmitoyl-coenzyme a desaturase, a possible key enzyme for temperature adaptation in Tetrahymena microsomes. (1) Microsomes from a thermotolerant Tetrahymena NT-1 catalyze the conversion of palmitoyl-CoA to palmitoleate. (2) Palmitoyl-CoA desaturase enzyme requires molecular oxygen and NADH or NADPH as cofactor and its activity is inhibited by cyanide. A pH optimum range 7.0--7.3 is observed. (3) There is a clear break at 30 degrees C and a slight bend around 15 degrees C in the Arrhenius plots of palmitoyl-CoA desaturase activity. (4) After quenching from 39.5 degrees C, at 26 degrees C microsomal membranes show small particle-free areas, when examined by freeze-fracture electron microscopy, indicating the onset of phase separation. Larger smooth areas devoid of membrane-intercalated particles are observed in microsomes at 23 and 15 degrees C. The results support evidence that the thermally induced transition of desaturase enzyme activity in related to the altered membrane properties due to temperature change."}
{"id": "PMID:20150", "title": "Neutral lipid biosynthesis in Mycobacterium smegmatis.", "content": "The biosynthesis of neutral lipids in Mycobacterium smegmatis was studied using cell free extracts. Maximum neutral lipid production was obtained when the reaction mixture (400 microliter) consisted of 0.25 M potassium phosphate buffer (pH 7.5), 0.125 mM oleoyl-CoA, 3.75 mM sn-glycerol-3-P, 10 mM MgCl2 and 1.85 mg bovine serum albumin. No magnesium dependency for the acylation of sn-glycerol-3-P was observed. A slight stabilizing effect seemed to occur due to this ion. The enzyme phosphatidate phosphohydrolase, on the other hand, was shown to be magnesium dependent. The activity of this enzyme also appeared to be stimulated by high concentration (0.75 to 1.25 mM) of ATP which enhanced lipid formation at all concentrations tested (0.25 to 3.75 mM). A heat-stable protective factor having a molecular weight less than 16 000 which caused a stimulatory effect on sn-glycerol 3-phosphate acyltransferase activity was found in the cell-free extracts. Preliminary experiments suggest that the factor might be polysaccharide in nature.", "contents": "Neutral lipid biosynthesis in Mycobacterium smegmatis. The biosynthesis of neutral lipids in Mycobacterium smegmatis was studied using cell free extracts. Maximum neutral lipid production was obtained when the reaction mixture (400 microliter) consisted of 0.25 M potassium phosphate buffer (pH 7.5), 0.125 mM oleoyl-CoA, 3.75 mM sn-glycerol-3-P, 10 mM MgCl2 and 1.85 mg bovine serum albumin. No magnesium dependency for the acylation of sn-glycerol-3-P was observed. A slight stabilizing effect seemed to occur due to this ion. The enzyme phosphatidate phosphohydrolase, on the other hand, was shown to be magnesium dependent. The activity of this enzyme also appeared to be stimulated by high concentration (0.75 to 1.25 mM) of ATP which enhanced lipid formation at all concentrations tested (0.25 to 3.75 mM). A heat-stable protective factor having a molecular weight less than 16 000 which caused a stimulatory effect on sn-glycerol 3-phosphate acyltransferase activity was found in the cell-free extracts. Preliminary experiments suggest that the factor might be polysaccharide in nature."}
{"id": "PMID:20151", "title": "Physicochemical and functional properties of Perinereis cultrifera (Gr\u00fcbe) erythrocruorin.", "content": "Perinereis erythrocruorin has the following physicochemical properties: So20,w = 55S, corresponding to a molecular weight around 2.7-10(6); minimum molecular weight (on the basis of the heme content) 23 700 +/- 500; isoelectric point 5.1; alpha-helix content approximately 40%. At alkaline pH values in the oxygenated form the 55-S molecules dissociate into subunits with a weight average sedimentation coefficient of 3S, corresponding to a molecular weight approximately 35 000. Deoxygenation of partially dissociated samples promotes association of the 3-S subunits into a 9S component. The functional properties of Perinereis erythrocruorin are characterized by a low cooperativity in oxygen binding (n 1/2 = 1.5) at neutral pH. Cooperativity increases reversibly towards both the acid and alkaline pH range, irrespective of changes in molecular weight. This finding, taken together with the ultracentrifuge results, suggests that a subunit may represent the functional unit of the protein. The pH dependence of the oxygen affinity can be accounted for in terms of a single oxygen linked group with a pK of 8.", "contents": "Physicochemical and functional properties of Perinereis cultrifera (Gr\u00fcbe) erythrocruorin. Perinereis erythrocruorin has the following physicochemical properties: So20,w = 55S, corresponding to a molecular weight around 2.7-10(6); minimum molecular weight (on the basis of the heme content) 23 700 +/- 500; isoelectric point 5.1; alpha-helix content approximately 40%. At alkaline pH values in the oxygenated form the 55-S molecules dissociate into subunits with a weight average sedimentation coefficient of 3S, corresponding to a molecular weight approximately 35 000. Deoxygenation of partially dissociated samples promotes association of the 3-S subunits into a 9S component. The functional properties of Perinereis erythrocruorin are characterized by a low cooperativity in oxygen binding (n 1/2 = 1.5) at neutral pH. Cooperativity increases reversibly towards both the acid and alkaline pH range, irrespective of changes in molecular weight. This finding, taken together with the ultracentrifuge results, suggests that a subunit may represent the functional unit of the protein. The pH dependence of the oxygen affinity can be accounted for in terms of a single oxygen linked group with a pK of 8."}
{"id": "PMID:20152", "title": "The pH dependence of the resonance raman spectra and structural alterations at heme moieties of various c-type cytochromes.", "content": "The pH dependence of resonance Raman spectra were studied for ferrous and ferric cytochromes c, c2, c3, c-551, and c-555. The frequencies of the 1565 cm-1 (ferric) and 1539 cm-1 lines (ferrous) were sensitive to the replacement of the sixth ligand. The titration curve for the 1565 cm-1 line of cytochrome c was parallel with that for the 695 nm band. The pH dependence of the 1539 cm-1 line of ferrous cytochrome c3 suggested the stepwise replacement of the sixth ligand of its four hemes, although such pH dependence was not recognized for the Raman spectra of other ferrous cytochromes investigated. The relative intensities of three Raman lines at 1639, 1587, and 1561 cm-1 of ferric protoporphyrin bis-imidazole complex were changed clearly by the presence of detergents. The relative intensities of the corresponding three Raman lines of cytochromes b5 and c were close to those of the ferric porphyrin complex in the presence and absence of detergents, respectively, suggesting an appreciable difference in their heme environments. Reduced hemin in detergent solution, unexpectedly, gave the Raman spectrum of ferric low spin type.", "contents": "The pH dependence of the resonance raman spectra and structural alterations at heme moieties of various c-type cytochromes. The pH dependence of resonance Raman spectra were studied for ferrous and ferric cytochromes c, c2, c3, c-551, and c-555. The frequencies of the 1565 cm-1 (ferric) and 1539 cm-1 lines (ferrous) were sensitive to the replacement of the sixth ligand. The titration curve for the 1565 cm-1 line of cytochrome c was parallel with that for the 695 nm band. The pH dependence of the 1539 cm-1 line of ferrous cytochrome c3 suggested the stepwise replacement of the sixth ligand of its four hemes, although such pH dependence was not recognized for the Raman spectra of other ferrous cytochromes investigated. The relative intensities of three Raman lines at 1639, 1587, and 1561 cm-1 of ferric protoporphyrin bis-imidazole complex were changed clearly by the presence of detergents. The relative intensities of the corresponding three Raman lines of cytochromes b5 and c were close to those of the ferric porphyrin complex in the presence and absence of detergents, respectively, suggesting an appreciable difference in their heme environments. Reduced hemin in detergent solution, unexpectedly, gave the Raman spectrum of ferric low spin type."}
{"id": "PMID:20153", "title": "Nuclear magnetic resonance studies of the denaturation of ubiquitin.", "content": "The effects of pH, temperature and guanidine hydrochloride concentration on the structure of ubiquitin, a polypeptide which can activate adenylate cyclase and can mimic thymopoietin induced differentiation of prothymocytes, were monitored using nuclear magnetic resonance spectroscopy. This relatively small polypeptide (molecular weight of 8541) exhibits a remarkable stability towards pH and temperature changes. At 7 M guanidine hydrochloride concentration, the structure of ubiquitin is essentially a random coil.", "contents": "Nuclear magnetic resonance studies of the denaturation of ubiquitin. The effects of pH, temperature and guanidine hydrochloride concentration on the structure of ubiquitin, a polypeptide which can activate adenylate cyclase and can mimic thymopoietin induced differentiation of prothymocytes, were monitored using nuclear magnetic resonance spectroscopy. This relatively small polypeptide (molecular weight of 8541) exhibits a remarkable stability towards pH and temperature changes. At 7 M guanidine hydrochloride concentration, the structure of ubiquitin is essentially a random coil."}
{"id": "PMID:20154", "title": "The binding of calcium to fibrinogen: some structural features.", "content": "Experiments are described which suggest that structural features are related to the existence of three high affinity calcium-binding sites in the fibrinogen molecule. The circular dichroism spectra analysis shows that the binding of calcium to this protein does not entail an overall conformational change. However several calcium-induced protective effects may be observed: 1. At pH 5.0 calcium-free fibrinogen is slightly acid-denatured. This denaturation is counteracted by the presence of calcium, whereas magnesium ions have no effect. 2. A temperature transition shift of 3 degrees C is measured in the presence of bound calcium during thermal denaturation, whereas magnesium ions have no effect. 3. Resistance to proteolysis by plasmin is observed when calcium is bound to fibrinogen. The velocity of the splitting of the earliest plasmin-succeptible bonds is reduced in the presence of calcium, whereas magnesium ions have no effect. It can be concluded from these results that the calcium binding centers are located in a more or less flexible zone of the molecule probably involving the C-terminal part of the Aalpha chain. And that the calcium divalent cation stabilizes a more compact structure of the fibrinogen molecule.", "contents": "The binding of calcium to fibrinogen: some structural features. Experiments are described which suggest that structural features are related to the existence of three high affinity calcium-binding sites in the fibrinogen molecule. The circular dichroism spectra analysis shows that the binding of calcium to this protein does not entail an overall conformational change. However several calcium-induced protective effects may be observed: 1. At pH 5.0 calcium-free fibrinogen is slightly acid-denatured. This denaturation is counteracted by the presence of calcium, whereas magnesium ions have no effect. 2. A temperature transition shift of 3 degrees C is measured in the presence of bound calcium during thermal denaturation, whereas magnesium ions have no effect. 3. Resistance to proteolysis by plasmin is observed when calcium is bound to fibrinogen. The velocity of the splitting of the earliest plasmin-succeptible bonds is reduced in the presence of calcium, whereas magnesium ions have no effect. It can be concluded from these results that the calcium binding centers are located in a more or less flexible zone of the molecule probably involving the C-terminal part of the Aalpha chain. And that the calcium divalent cation stabilizes a more compact structure of the fibrinogen molecule."}
{"id": "PMID:20155", "title": "Physicochemical evidence for the existence of two pyridoxal 5'-phosphate binding sites on glutamate dehydrogenase and characterization of their functional role.", "content": "Kinetic studies of pyridoxal 5'-phosphate binding to glutamate dehydrogenase (EC 1.4.1.3) has provided evidence for two specific binding sites, chemically identified as Lys 126 and Lys 333. Use of protecting ligands permitted the selective modification of only one of these lysines, and showed that (1) Lys 333 modification results in depolymerisation of the enzyme into active hexamers; (2) Lys 126-modified enzyme was 92% inactivated. The residual activity was desensitized to GTP. The inactivation process was cooperative, maximum inactivation occurring as soon as half of the Lys 126 were modified.", "contents": "Physicochemical evidence for the existence of two pyridoxal 5'-phosphate binding sites on glutamate dehydrogenase and characterization of their functional role. Kinetic studies of pyridoxal 5'-phosphate binding to glutamate dehydrogenase (EC 1.4.1.3) has provided evidence for two specific binding sites, chemically identified as Lys 126 and Lys 333. Use of protecting ligands permitted the selective modification of only one of these lysines, and showed that (1) Lys 333 modification results in depolymerisation of the enzyme into active hexamers; (2) Lys 126-modified enzyme was 92% inactivated. The residual activity was desensitized to GTP. The inactivation process was cooperative, maximum inactivation occurring as soon as half of the Lys 126 were modified."}
{"id": "PMID:20157", "title": "The isolation and characterization of a colony stimulating factor from human lung.", "content": "Serum-free conditioned medium from human lung obtained at autopsy provides a rich source of colony stimulating factor which stimulates granulocytic and macrophagic colony growth in both mouse and human bone marrow. The appearance of the factor is enhanced by endotoxin and inhibited by either puromycin or actinomycin D. Human lung colony stimulating factor is stable at the pH range of 6.5-10 and temperature of 56 degrees C for 30 min. It is resistant to trypsin and neuraminidase but is sensitive to subtilisin, chymotrypsin and periodate. It shows heterogeneity on Sephadex gel filtration with two activity peaks having molecular weight of 200 000 and 40 000, respectively. Upon gel electrophoresis, human lung colony stimulating factor migrates in the alpha-globulin post-albumin region. Using the combination procedures of hydroxyapatite chromatography and preparative polyacrylamide gel electrophoresis a 600-fold purification was achieved with a final specific activity of 6-10(5) units per mg protein. The purified colony stimulating factor is very labile; however, the activity can be stabilized by the addition of gelatin or bovine serum albumin at the concentration of 0.1% and 0.2 mg/ml, respectively.", "contents": "The isolation and characterization of a colony stimulating factor from human lung. Serum-free conditioned medium from human lung obtained at autopsy provides a rich source of colony stimulating factor which stimulates granulocytic and macrophagic colony growth in both mouse and human bone marrow. The appearance of the factor is enhanced by endotoxin and inhibited by either puromycin or actinomycin D. Human lung colony stimulating factor is stable at the pH range of 6.5-10 and temperature of 56 degrees C for 30 min. It is resistant to trypsin and neuraminidase but is sensitive to subtilisin, chymotrypsin and periodate. It shows heterogeneity on Sephadex gel filtration with two activity peaks having molecular weight of 200 000 and 40 000, respectively. Upon gel electrophoresis, human lung colony stimulating factor migrates in the alpha-globulin post-albumin region. Using the combination procedures of hydroxyapatite chromatography and preparative polyacrylamide gel electrophoresis a 600-fold purification was achieved with a final specific activity of 6-10(5) units per mg protein. The purified colony stimulating factor is very labile; however, the activity can be stabilized by the addition of gelatin or bovine serum albumin at the concentration of 0.1% and 0.2 mg/ml, respectively."}
{"id": "PMID:20161", "title": "[Analysis of the activity of Micrococcus luteus endonucleases with respect to gamma-irradiated DNA].", "content": "Endonucleases from Micrococcus luteus that induce single-strand breaks in gamma-irradiated DNA have been separated chromatographycally into two groups. The first group involves two different enzymes: AP-endonuclease II (mol. weight 30 000) and AP, UV-endonuclease I (mol. weight 15 000) that recognize alkali-labile lesions in gamma-irradiated DNA and apurinic sites in DNA heated at 70 degrees C, pH 6.08 AP-endonuclease II in cooperation with DNA polymerase from M. luteus and T4 phage-induced polynucleotide ligase is capable of carrying out in vitro complete excision repair of alkali-labile lesins in gamma-irradiated DNA. The second group involves gamma-endonucleases X and Y that act on alkalistable gamma-ray lesions. gamma-endonucleases X and Y can be separated by chromatography on DEAE-cellulose but possess similar properties. Activity of gamma-endonucleases toward gamma-irradiated DNA is inhibited by only heavily UV-irradiated DNA (15 000 ergs/mm2). The data are consistent with the hypothesis that gamma-endonucleases are specific for thymine glycols (t' and tUV) in UV- and gamma-irradiated DNA.", "contents": "[Analysis of the activity of Micrococcus luteus endonucleases with respect to gamma-irradiated DNA]. Endonucleases from Micrococcus luteus that induce single-strand breaks in gamma-irradiated DNA have been separated chromatographycally into two groups. The first group involves two different enzymes: AP-endonuclease II (mol. weight 30 000) and AP, UV-endonuclease I (mol. weight 15 000) that recognize alkali-labile lesions in gamma-irradiated DNA and apurinic sites in DNA heated at 70 degrees C, pH 6.08 AP-endonuclease II in cooperation with DNA polymerase from M. luteus and T4 phage-induced polynucleotide ligase is capable of carrying out in vitro complete excision repair of alkali-labile lesins in gamma-irradiated DNA. The second group involves gamma-endonucleases X and Y that act on alkalistable gamma-ray lesions. gamma-endonucleases X and Y can be separated by chromatography on DEAE-cellulose but possess similar properties. Activity of gamma-endonucleases toward gamma-irradiated DNA is inhibited by only heavily UV-irradiated DNA (15 000 ergs/mm2). The data are consistent with the hypothesis that gamma-endonucleases are specific for thymine glycols (t' and tUV) in UV- and gamma-irradiated DNA."}
{"id": "PMID:20162", "title": "[Properties of human creatine kinase isoenzymes].", "content": "Properties of human creatine kinase isoenzymes (MM, MB and BB) are investigated. The most pronounced differences in properties of these isoenzymes are found under their urea inactivation, heat denaturation and the inhibition by rabbit antisera to isoenzymes. Differences in values of the Mikhaelis constant and substrate and pH dependencies are much less pronounced. The presence of ADP stabilizes creatine kinase isoenzymes under conditions of urea and heat inactivation. Properties of hybrid MB isoenzymes are found to be intermediate with respect to MM and BB isoenzymes. A mode of the interaction of M and B subunits in dimeric molecules of creatine kinase isoenzymes is discussed.", "contents": "[Properties of human creatine kinase isoenzymes]. Properties of human creatine kinase isoenzymes (MM, MB and BB) are investigated. The most pronounced differences in properties of these isoenzymes are found under their urea inactivation, heat denaturation and the inhibition by rabbit antisera to isoenzymes. Differences in values of the Mikhaelis constant and substrate and pH dependencies are much less pronounced. The presence of ADP stabilizes creatine kinase isoenzymes under conditions of urea and heat inactivation. Properties of hybrid MB isoenzymes are found to be intermediate with respect to MM and BB isoenzymes. A mode of the interaction of M and B subunits in dimeric molecules of creatine kinase isoenzymes is discussed."}
{"id": "PMID:20163", "title": "[Soluble high molecular weight derivatives of trypsin pancreatic inhibitor. Isolation and properties of dextran-bound pancreatic inhibitor].", "content": "A method of isolating preparations of pancreatic inhibitor of trypsin, bound with soluble polysaccharide carriers, is worked out. It is demonstrated that the reaction of a pancreatic inhibitor and cyanuric chloride-activated dextran proceeds for OH groups of tyrosine residues and for-epsilon-NH2 groups of lysine residues. A method is offered of the protection of amino groups with citraconic anhydride for the complete retaining of the inhibitory activity during attachment to dextran. Thermic denaturation of pancreatic inhibitor preparations at pH 4.7 and 97 degrees C is studied. It is found that the modification by 2-amino-4.6-dichloro-s-triazine stabilizes the protein molecule, while the interaction with the matrix of soluble dextran does not carry any contribution to thermostability of the pancreatic inhibitor.", "contents": "[Soluble high molecular weight derivatives of trypsin pancreatic inhibitor. Isolation and properties of dextran-bound pancreatic inhibitor]. A method of isolating preparations of pancreatic inhibitor of trypsin, bound with soluble polysaccharide carriers, is worked out. It is demonstrated that the reaction of a pancreatic inhibitor and cyanuric chloride-activated dextran proceeds for OH groups of tyrosine residues and for-epsilon-NH2 groups of lysine residues. A method is offered of the protection of amino groups with citraconic anhydride for the complete retaining of the inhibitory activity during attachment to dextran. Thermic denaturation of pancreatic inhibitor preparations at pH 4.7 and 97 degrees C is studied. It is found that the modification by 2-amino-4.6-dichloro-s-triazine stabilizes the protein molecule, while the interaction with the matrix of soluble dextran does not carry any contribution to thermostability of the pancreatic inhibitor."}
{"id": "PMID:20164", "title": "[Comparative kinetic studies of Mg2+-activated hydrolysis of tripolyphosphate and pyrophosphate by inorganic pyrophosphatase].", "content": "Computer analysis of P3 and pyrophosphate conversion rate dependence on substrate and metal-activator concentrations reveals the identity of kinetic patterns. Dissociation and catalytical constants for the enzyme combinations with two types of metal-substrates complexes, MS and M2S, at pH 9.0 are by one to two orders of magnitude \"poorer\" for P3 as compared to PPi. Optimal pH value for the hydrolysis of P3 is by 2 units higher than this for the hydrolysis of PPi. pH profiles for the kinetic parameters in the pH range 8.0--9.5 differ considerably for the two substrates, presumably due to the existence of additional catalitically important ionisations in the reaction with P3.", "contents": "[Comparative kinetic studies of Mg2+-activated hydrolysis of tripolyphosphate and pyrophosphate by inorganic pyrophosphatase]. Computer analysis of P3 and pyrophosphate conversion rate dependence on substrate and metal-activator concentrations reveals the identity of kinetic patterns. Dissociation and catalytical constants for the enzyme combinations with two types of metal-substrates complexes, MS and M2S, at pH 9.0 are by one to two orders of magnitude \"poorer\" for P3 as compared to PPi. Optimal pH value for the hydrolysis of P3 is by 2 units higher than this for the hydrolysis of PPi. pH profiles for the kinetic parameters in the pH range 8.0--9.5 differ considerably for the two substrates, presumably due to the existence of additional catalitically important ionisations in the reaction with P3."}
{"id": "PMID:20160", "title": "[Localization of unpaired electrons in molecules of the substrate inhibitors of lysozyme. II. Oligosaccharides].", "content": "It has been shown by the method of electron photosensitized transfer that N-acetyl group is the main electron-acceptor group in oligomeres of N-acetyl glucose amine (AGA). In n-AGA molecules (n-3.5) interacting with an electron radical products of the breakage of glycoside bond are observed, their concentration rising with an increase of the chain length. The ionic strength does not affect the photosensitized transfer of the electron in chitin oligomeres. Formation of paramagnetic centres in the molecule penta-AGA depends on the medium pH.", "contents": "[Localization of unpaired electrons in molecules of the substrate inhibitors of lysozyme. II. Oligosaccharides]. It has been shown by the method of electron photosensitized transfer that N-acetyl group is the main electron-acceptor group in oligomeres of N-acetyl glucose amine (AGA). In n-AGA molecules (n-3.5) interacting with an electron radical products of the breakage of glycoside bond are observed, their concentration rising with an increase of the chain length. The ionic strength does not affect the photosensitized transfer of the electron in chitin oligomeres. Formation of paramagnetic centres in the molecule penta-AGA depends on the medium pH."}
{"id": "PMID:20165", "title": "[Solubilization and reconstruction of microsomal AMP-deaminase from skeletal muscles].", "content": "Microsomal AMP-deaminase was solubilized by 0.5 M KCl after treatment of microsomal membranes with 0.12 M KCl. Using disc-electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate one major protein component (mol. weight about 90 000) and three minor ones with molecular weights of 110 000, 80 000, and 60 000 were found in the soluble fraction. In addition to proteins, the fraction was found in the soluble fraction. In addition to proteins, the fraction was found to contain a small amount of phospholipids. The deaminase found in the solution may be reconstructed into the membranes at a decrease in KCl concentration, part of enzyme being bound in the inactive form under excess of the soluble fraction. Deaminase binding to the membranes is unaffected by the changes within the pH range of 6.2--7.8 and temperature range of 4--10 degrees C. It is assumed that AMP-deaminase is bound to other membrane components by electrostatic bonds.", "contents": "[Solubilization and reconstruction of microsomal AMP-deaminase from skeletal muscles]. Microsomal AMP-deaminase was solubilized by 0.5 M KCl after treatment of microsomal membranes with 0.12 M KCl. Using disc-electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate one major protein component (mol. weight about 90 000) and three minor ones with molecular weights of 110 000, 80 000, and 60 000 were found in the soluble fraction. In addition to proteins, the fraction was found in the soluble fraction. In addition to proteins, the fraction was found to contain a small amount of phospholipids. The deaminase found in the solution may be reconstructed into the membranes at a decrease in KCl concentration, part of enzyme being bound in the inactive form under excess of the soluble fraction. Deaminase binding to the membranes is unaffected by the changes within the pH range of 6.2--7.8 and temperature range of 4--10 degrees C. It is assumed that AMP-deaminase is bound to other membrane components by electrostatic bonds."}
{"id": "PMID:20166", "title": "[Purification and properties of NADP-reductase of phototropic bacteria Thiocapsa roseopersicina].", "content": "The method of purification up to homogenous states and properties of NADP-reductase of purple bacteria Thiocapsa roseopersicina, strain BBS, are described. The molecular weight of NADP-reductase is about 47 000; it is flavoprotein consisting of two subunits. Atebrim and chloromercury bensoate inhibit the activity of NADP-reductase (34% and 33--60%, respectively). The enzyme is specific to NADPH; it catalyzes menadion-reductase reaction, diaphorase reaction of benzyl viologen reduction, oxidation of reduced benzyl viologen in the presence of NADP, reduction of ferredoxin and cytochrome c in the presence of NADPH, but it is not capable to catalyze transhydrogenase reaction.", "contents": "[Purification and properties of NADP-reductase of phototropic bacteria Thiocapsa roseopersicina]. The method of purification up to homogenous states and properties of NADP-reductase of purple bacteria Thiocapsa roseopersicina, strain BBS, are described. The molecular weight of NADP-reductase is about 47 000; it is flavoprotein consisting of two subunits. Atebrim and chloromercury bensoate inhibit the activity of NADP-reductase (34% and 33--60%, respectively). The enzyme is specific to NADPH; it catalyzes menadion-reductase reaction, diaphorase reaction of benzyl viologen reduction, oxidation of reduced benzyl viologen in the presence of NADP, reduction of ferredoxin and cytochrome c in the presence of NADPH, but it is not capable to catalyze transhydrogenase reaction."}
{"id": "PMID:20167", "title": "[Free radical peroxidation of liver mitochondrial and microsomal phospholipids in rat postnatal development].", "content": "Activities of both non-enzymic (ascorbate-dependent) and enzymic NADPH-dependent) peroxidation of microsomal and mitochondrial phospholipids are found to be increased in rat liver during postnatal development. It is suggested, that microsomal NADPH-dependent phospholipid dioxygenase forming a chemical modification of membrane polyenic acyls, can be a factor regulating the activities of membrane-linked enzymes under normal physiological processes.", "contents": "[Free radical peroxidation of liver mitochondrial and microsomal phospholipids in rat postnatal development]. Activities of both non-enzymic (ascorbate-dependent) and enzymic NADPH-dependent) peroxidation of microsomal and mitochondrial phospholipids are found to be increased in rat liver during postnatal development. It is suggested, that microsomal NADPH-dependent phospholipid dioxygenase forming a chemical modification of membrane polyenic acyls, can be a factor regulating the activities of membrane-linked enzymes under normal physiological processes."}
{"id": "PMID:20168", "title": "[Some features of cyclic adenosine monophosphate metabolism in mouse liver and hepatoma 22].", "content": "The levels of cyclic adenosine monophosphate (cAMP) and two forms of cAMP phosphodiesterase with low (PDE1) and high (PDE2) affinity for the substrate were determined in homogenates from mouse liver and transplanted hepatoma 22. The level of cAMP in the tumour is 3 times lower than that in liver. By te kinetic parameters (Vmax, Km, pH optimum) adenylate cyclase from tumour does not show any significant differences as compared to the liver enzyme; the enzyme from hepatoma is, however, more sensitive to activation by F- ions. The activities of adenylate cyclase in liver and tumour cells are the same. Phosphodiesterases of cAMP from tumour and liver cells are similar in their Km values (3,3-10(-4) M for PDE1 and 2-10(-6) M for PDE2); however, the maximal and real rates of cAMP hydrolysis in hepatoma are much higher than in liver. The fact that both cAMP phosphodiesterase activities have similar dependence on Mg2+ and Ca2+ concentrations, suggests that PDE1 is a latent form of PDE2. In tumour cells the equilibrium between these two forms is probably shifted towards the enzyme with high affinity for the substrate. The results suggest that a decreased cAMP level in hepatoma cells (as compared to the liver) is due to the activation of PDE2.", "contents": "[Some features of cyclic adenosine monophosphate metabolism in mouse liver and hepatoma 22]. The levels of cyclic adenosine monophosphate (cAMP) and two forms of cAMP phosphodiesterase with low (PDE1) and high (PDE2) affinity for the substrate were determined in homogenates from mouse liver and transplanted hepatoma 22. The level of cAMP in the tumour is 3 times lower than that in liver. By te kinetic parameters (Vmax, Km, pH optimum) adenylate cyclase from tumour does not show any significant differences as compared to the liver enzyme; the enzyme from hepatoma is, however, more sensitive to activation by F- ions. The activities of adenylate cyclase in liver and tumour cells are the same. Phosphodiesterases of cAMP from tumour and liver cells are similar in their Km values (3,3-10(-4) M for PDE1 and 2-10(-6) M for PDE2); however, the maximal and real rates of cAMP hydrolysis in hepatoma are much higher than in liver. The fact that both cAMP phosphodiesterase activities have similar dependence on Mg2+ and Ca2+ concentrations, suggests that PDE1 is a latent form of PDE2. In tumour cells the equilibrium between these two forms is probably shifted towards the enzyme with high affinity for the substrate. The results suggest that a decreased cAMP level in hepatoma cells (as compared to the liver) is due to the activation of PDE2."}
{"id": "PMID:20169", "title": "Comparison of postnatal development of several acid glycosidases in the rat forebrain and cerebellum.", "content": "Changes of activity of several glycosidases (beta-galactosidase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, alpha-D-mannosidase and alpha-L-fucosidase) were compared in the forebrain and cerebellum during postnatal development of the rat. Detailed analysis of the data showed similarities, but also substantial differences in their development in both organs. This is interpreted  as an indication of the presence of common regulatory mechanisms, as well as of other factors which differently influence development of the glycosidases studied in both CNS parts.", "contents": "Comparison of postnatal development of several acid glycosidases in the rat forebrain and cerebellum. Changes of activity of several glycosidases (beta-galactosidase, beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, alpha-D-mannosidase and alpha-L-fucosidase) were compared in the forebrain and cerebellum during postnatal development of the rat. Detailed analysis of the data showed similarities, but also substantial differences in their development in both organs. This is interpreted  as an indication of the presence of common regulatory mechanisms, as well as of other factors which differently influence development of the glycosidases studied in both CNS parts."}
{"id": "PMID:20170", "title": "Dissociation of growth hormone and prolactin response to levodopa during pyridoxine administration.", "content": "500 mg of levodopa was administered orally to 8 normal subjects and induced an increase of growth hormone (GH) and a decrease of prolactin (PRL) secretion. The levodopa-induced GH release was inhibited by an intravenous infusion of pyridoxine; on the contrary, the PRL response to levodopa was enhanced by pyridoxine infusion. This dissociation of GH and PRL responses to levodopa during pyridoxine infusion appears to be mediated by peripheral acceleration of the conversion of levodopa to dopamine. Since dopamine does not penetrate the blood-brain barrier, the enhanced PRL decrease observed during pyridoxine infusion might be explained only on the basis of a mechanism of action exerted by dopamine on extra blood-brain barrier sites.", "contents": "Dissociation of growth hormone and prolactin response to levodopa during pyridoxine administration. 500 mg of levodopa was administered orally to 8 normal subjects and induced an increase of growth hormone (GH) and a decrease of prolactin (PRL) secretion. The levodopa-induced GH release was inhibited by an intravenous infusion of pyridoxine; on the contrary, the PRL response to levodopa was enhanced by pyridoxine infusion. This dissociation of GH and PRL responses to levodopa during pyridoxine infusion appears to be mediated by peripheral acceleration of the conversion of levodopa to dopamine. Since dopamine does not penetrate the blood-brain barrier, the enhanced PRL decrease observed during pyridoxine infusion might be explained only on the basis of a mechanism of action exerted by dopamine on extra blood-brain barrier sites."}
{"id": "PMID:20171", "title": "Isoelectric focusing of interacting systems. I. Carrier ampholyte-induced macromolecular isomerization.", "content": "A phenomenological theory of isoelectric focusing is formulated for rapidly reversible, ampholyte-induced macromolecular isomerization. The calculations reveal that such interactions can give well resolved, bimodal transient and equilibrium isoelectric focusing patterns in which the two peaks correspond to different chemical equilibrium compositions and not to separated isomers. The kinetics of approach to the equilibrium pattern are characteristically biphasic: During the first phase, which is controlled by the rate of migration of the isomers in the electric field, two peaks are positioned in the region between the isoelectric points of the two isomers; one of the peaks then grows slowly at the expense of the other with a diffusion-dominated rate. The kinetics are dependent upon the initial distribution of macromolecule in the isoelectric focusing column, and in certain cases only a single peak is apparent during the first phase. These findings have practical implications for unambiguous interpretation of isoelectric focusing patterns, furnish explanations for hitherto puzzling experimental observations, and provide theoretical insights required for application of isoelectric focusing to the detection and characterization of macromolecular interactions in general.", "contents": "Isoelectric focusing of interacting systems. I. Carrier ampholyte-induced macromolecular isomerization. A phenomenological theory of isoelectric focusing is formulated for rapidly reversible, ampholyte-induced macromolecular isomerization. The calculations reveal that such interactions can give well resolved, bimodal transient and equilibrium isoelectric focusing patterns in which the two peaks correspond to different chemical equilibrium compositions and not to separated isomers. The kinetics of approach to the equilibrium pattern are characteristically biphasic: During the first phase, which is controlled by the rate of migration of the isomers in the electric field, two peaks are positioned in the region between the isoelectric points of the two isomers; one of the peaks then grows slowly at the expense of the other with a diffusion-dominated rate. The kinetics are dependent upon the initial distribution of macromolecule in the isoelectric focusing column, and in certain cases only a single peak is apparent during the first phase. These findings have practical implications for unambiguous interpretation of isoelectric focusing patterns, furnish explanations for hitherto puzzling experimental observations, and provide theoretical insights required for application of isoelectric focusing to the detection and characterization of macromolecular interactions in general."}
{"id": "PMID:20172", "title": "Isoelectric focusing of interacting systems. II. pH-dependent conformational transitions.", "content": "Transient and equilibrium isoelectric focusing patterns have been computed for pH-dependent conformational transitions in the limits of complete cooperativity and instantaneous chemical equilibration. Transitions induced by the binding of a relatively large number of hydrogen ions by the macromolecule give well resolved bimodal equilibrium patterns, provided that the resulting conformer has the lower isoelectric point. The corresponding transient patterns may be either bimodal or virtually unimodal for practical times of operation depending upon the point of insertion of the sample into the pH gradient and the stoichiometry of the interaction. A macromolecule undergoing sequential transitions can give multimodal isoelectric focussing patterns.", "contents": "Isoelectric focusing of interacting systems. II. pH-dependent conformational transitions. Transient and equilibrium isoelectric focusing patterns have been computed for pH-dependent conformational transitions in the limits of complete cooperativity and instantaneous chemical equilibration. Transitions induced by the binding of a relatively large number of hydrogen ions by the macromolecule give well resolved bimodal equilibrium patterns, provided that the resulting conformer has the lower isoelectric point. The corresponding transient patterns may be either bimodal or virtually unimodal for practical times of operation depending upon the point of insertion of the sample into the pH gradient and the stoichiometry of the interaction. A macromolecule undergoing sequential transitions can give multimodal isoelectric focussing patterns."}
{"id": "PMID:20173", "title": "Rheology of fibrin clots. IV. Darcy constants and fiber thickness.", "content": "Measurements of small oscillatory deformations of a fibrin clot by axial motion of a rod in a closed tube reveal an anomalous mechanical loss due to permeation of fluid through the clot structure. The Darcy constant for permeation can be calculated from data at the frequency where the apparent storage and loss shear moduli are equal, without the necessity of measurements at much lower frequencies as previously employed. From the Darcy constant, the average number of fibrin monomer units (v) per cross-section of a fibrous element of the clot can be calculated; it ranges from 4 to several hundred. In the range of fibrin concentration(c) from 3 to 14 milligrams, v is approximately proportional to c-2 for clots of coarse structure and to c-0.5 for clots of fine structure.", "contents": "Rheology of fibrin clots. IV. Darcy constants and fiber thickness. Measurements of small oscillatory deformations of a fibrin clot by axial motion of a rod in a closed tube reveal an anomalous mechanical loss due to permeation of fluid through the clot structure. The Darcy constant for permeation can be calculated from data at the frequency where the apparent storage and loss shear moduli are equal, without the necessity of measurements at much lower frequencies as previously employed. From the Darcy constant, the average number of fibrin monomer units (v) per cross-section of a fibrous element of the clot can be calculated; it ranges from 4 to several hundred. In the range of fibrin concentration(c) from 3 to 14 milligrams, v is approximately proportional to c-2 for clots of coarse structure and to c-0.5 for clots of fine structure."}
{"id": "PMID:20174", "title": "The CO and NO Bohr effect of human hemoglobin with and without inositolhexaphosphate.", "content": "Using NO and CO as ligands the Bohr effect of human hemoglobin has been measured with and without inositolhexophosphate. It appears that in the absence and presence of inositolhexaphosphate hemoglobin shows a distinct ligand specificity with respect to the Bohr effect. Ligation with NO is accompanied by release of a larger number of Bohr effect. It is shown that this latter result is due to the fact that the number of protons taken up upon binding of inositolhexaphosphate to ligated hemoglobin is larger for HbNO than for HbCO. It is suggested that this additional proton uptake is partially due to a restoration of the saltbridge between His 146beta and Asp 94beta upon addition of IHP.", "contents": "The CO and NO Bohr effect of human hemoglobin with and without inositolhexaphosphate. Using NO and CO as ligands the Bohr effect of human hemoglobin has been measured with and without inositolhexophosphate. It appears that in the absence and presence of inositolhexaphosphate hemoglobin shows a distinct ligand specificity with respect to the Bohr effect. Ligation with NO is accompanied by release of a larger number of Bohr effect. It is shown that this latter result is due to the fact that the number of protons taken up upon binding of inositolhexaphosphate to ligated hemoglobin is larger for HbNO than for HbCO. It is suggested that this additional proton uptake is partially due to a restoration of the saltbridge between His 146beta and Asp 94beta upon addition of IHP."}
{"id": "PMID:20175", "title": "1H Nmr studies at 360 MHz of the methyl groups in native and chemically modified basic pancreatic trypsin inhibitor (BPTI).", "content": "In the 1H NMR spectra obtained at 360 MHz after digital resolution enhancement, the multiplet resonances of the methyl groups in the basic pancreatic trypsin inhibitor (BPTI) were resolved. With suitable double irradiation techniques the individual methyl resonances were assigned to the different types of aliphatic amino acid residues. Furthermore, from pH titration and comparison of the native protein with chemically modified BPTI, the resonance lines of Ala 16 in the active site and Ala 58 at the C-terminus were identified. Potential applications of the resolved methyl resonances as natural NMR probes for studies of the molecular conformation are discussed.", "contents": "1H Nmr studies at 360 MHz of the methyl groups in native and chemically modified basic pancreatic trypsin inhibitor (BPTI). In the 1H NMR spectra obtained at 360 MHz after digital resolution enhancement, the multiplet resonances of the methyl groups in the basic pancreatic trypsin inhibitor (BPTI) were resolved. With suitable double irradiation techniques the individual methyl resonances were assigned to the different types of aliphatic amino acid residues. Furthermore, from pH titration and comparison of the native protein with chemically modified BPTI, the resonance lines of Ala 16 in the active site and Ala 58 at the C-terminus were identified. Potential applications of the resolved methyl resonances as natural NMR probes for studies of the molecular conformation are discussed."}
{"id": "PMID:20178", "title": "Compartmentalization in proteinoid microspheres.", "content": "Proteinoid microspheres with stable internal compartments and internal structure are made from acidic proteinoid and basic proteinoid with calcium. The populations of microspheres are characterized by a wide diversity of structure. A model of primitive intracellular communication is suggested by the observed movement of internal particles between compartments of a multicompartmentalized unit. Differential response to pH change and to temperature change has been demonstrated within one population and suggests one mode of adaptive selection among primordial cell populations.", "contents": "Compartmentalization in proteinoid microspheres. Proteinoid microspheres with stable internal compartments and internal structure are made from acidic proteinoid and basic proteinoid with calcium. The populations of microspheres are characterized by a wide diversity of structure. A model of primitive intracellular communication is suggested by the observed movement of internal particles between compartments of a multicompartmentalized unit. Differential response to pH change and to temperature change has been demonstrated within one population and suggests one mode of adaptive selection among primordial cell populations."}
{"id": "PMID:20180", "title": "Life on Mars? The Viking labeled release experiment.", "content": "Viking radiorespirometry (\"Labeled Release\" [LR]) experiments conducted on surface material obtained at two sites on Mars have produced results which on Earth would clearly establish the presence of microbial activity in the soil. However, two factors on Mars keep the question open. First, the intense UV flux striking Mars has given rise to several theories postulating the production of highly oxidative compounds. Such compounds might be responsible for the observed results. Second, the molecular analysis experiment has not found organic matter in the Mars surface material, and therefore, does not support the presence of roganisms. However, sensitivity limitations of the organic analysis instrument could permit as many as one million terrestrial type bacteria to go undetected. Terrestrial experiments with UV irradiation of Mars Analog Soil did not produce Mars type LR results. Gamma irradiation of silica gel did produce positive results, but not mimicking those on Mars. The life question remains open.", "contents": "Life on Mars? The Viking labeled release experiment. Viking radiorespirometry (\"Labeled Release\" [LR]) experiments conducted on surface material obtained at two sites on Mars have produced results which on Earth would clearly establish the presence of microbial activity in the soil. However, two factors on Mars keep the question open. First, the intense UV flux striking Mars has given rise to several theories postulating the production of highly oxidative compounds. Such compounds might be responsible for the observed results. Second, the molecular analysis experiment has not found organic matter in the Mars surface material, and therefore, does not support the presence of roganisms. However, sensitivity limitations of the organic analysis instrument could permit as many as one million terrestrial type bacteria to go undetected. Terrestrial experiments with UV irradiation of Mars Analog Soil did not produce Mars type LR results. Gamma irradiation of silica gel did produce positive results, but not mimicking those on Mars. The life question remains open."}
{"id": "PMID:20181", "title": "A possible prebiotic synthesis of thymine: uracil-formaldehyde-formic acid reaction.", "content": "When uracil is reacted with formaldehyde and formic acid in dilute aqueous solutions at 100-140 degrees C, 5-hydroxymethyluracil (5-HMU), methylenebiuracil (MBU) and thymine are formed. It has been shown that 5-HMU is an intermediate in the formation of MBU and thymine. In the presence of formic acid, 5-HMU gives MBU, thymine and in some cases uracil. The formation of thymine is generally favoured under acidic conditions, although small amounts of this base could also be obtained when the reactions were carried out under mildly basic conditions. A hydride ion transfer mechanism is suggested for some of these reactions. These results have relevance to the formation of thymine under prebiotic conditions.", "contents": "A possible prebiotic synthesis of thymine: uracil-formaldehyde-formic acid reaction. When uracil is reacted with formaldehyde and formic acid in dilute aqueous solutions at 100-140 degrees C, 5-hydroxymethyluracil (5-HMU), methylenebiuracil (MBU) and thymine are formed. It has been shown that 5-HMU is an intermediate in the formation of MBU and thymine. In the presence of formic acid, 5-HMU gives MBU, thymine and in some cases uracil. The formation of thymine is generally favoured under acidic conditions, although small amounts of this base could also be obtained when the reactions were carried out under mildly basic conditions. A hydride ion transfer mechanism is suggested for some of these reactions. These results have relevance to the formation of thymine under prebiotic conditions."}
{"id": "PMID:20182", "title": "Chemical evolution XXIX. Pyrimidines from hydrogen cyanide.", "content": "Dilute (0.1 M) solutions of HCN condense to oligomers at pH 8-9. Hydrolysis of these oligomers at pH 8.5 or with 6 N HCl yields 4,5-dihydroxypyrimidine, as the most abundant pyrimidine product along with orotic acid and 5-hydroxyuracil. These results, together with the earlier data, demonstrate that the three major nitrogen-containing classes of biomolecules could have originated from HCN on the primitive earth. The observation of the formation of orotic acid and 4-aminoimidazole-5-carboxamide by the hydrolysis of the HCN oligomers suggests that once the initially formed pyrimidines and purines were consumed, those life forms persisted which evolved enzymes for conversion of these intermediates to the pyrimidines and purines present in contemporary RNA.", "contents": "Chemical evolution XXIX. Pyrimidines from hydrogen cyanide. Dilute (0.1 M) solutions of HCN condense to oligomers at pH 8-9. Hydrolysis of these oligomers at pH 8.5 or with 6 N HCl yields 4,5-dihydroxypyrimidine, as the most abundant pyrimidine product along with orotic acid and 5-hydroxyuracil. These results, together with the earlier data, demonstrate that the three major nitrogen-containing classes of biomolecules could have originated from HCN on the primitive earth. The observation of the formation of orotic acid and 4-aminoimidazole-5-carboxamide by the hydrolysis of the HCN oligomers suggests that once the initially formed pyrimidines and purines were consumed, those life forms persisted which evolved enzymes for conversion of these intermediates to the pyrimidines and purines present in contemporary RNA."}
{"id": "PMID:20183", "title": "The mechanism of clay catalyzed polymerization of amino acid adenylates.", "content": "Amino acid adenylates were adsorbed on montmorillonite when either the interspatial faces or the edges of the latter were blocked. By this method it could be observed that adsorption of the amino acid adenylates takes place mostly on the planes of the clay. However, for polymerization to take place, the edges of the clay have to be free as well and apparently only these molecules polymerize which are attached to the planes of the clay by their amino groups and to the edges of the clay by their phosphate group. Thus all the charges of the molecules which might produce their repulsion from each other would be neutralized. As a consequence of these attachments polymerization on the clay would take place on its planar sites, but only on those neighboring its edges. The question whether neutralization of charges is also the reason why biochemical substrates have to attach themselves by several points to enzymes and thus make biochemistry fit into the framework of general chemistry, is raised.", "contents": "The mechanism of clay catalyzed polymerization of amino acid adenylates. Amino acid adenylates were adsorbed on montmorillonite when either the interspatial faces or the edges of the latter were blocked. By this method it could be observed that adsorption of the amino acid adenylates takes place mostly on the planes of the clay. However, for polymerization to take place, the edges of the clay have to be free as well and apparently only these molecules polymerize which are attached to the planes of the clay by their amino groups and to the edges of the clay by their phosphate group. Thus all the charges of the molecules which might produce their repulsion from each other would be neutralized. As a consequence of these attachments polymerization on the clay would take place on its planar sites, but only on those neighboring its edges. The question whether neutralization of charges is also the reason why biochemical substrates have to attach themselves by several points to enzymes and thus make biochemistry fit into the framework of general chemistry, is raised."}
{"id": "PMID:20184", "title": "Comparison of polymerization of ancrod and thrombin fibrin monomers.", "content": "The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy.", "contents": "Comparison of polymerization of ancrod and thrombin fibrin monomers. The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy."}
{"id": "PMID:20185", "title": "Allogeneic bone marrow transplantation in conventional mice: I. Effect of antibiotic therapy on long term survival of allogeneic chimeras.", "content": "In the present communication the beneficial effect of long term antimicrobial treatment with poorly absorbable antiboitics on the survival of allogeneic bone marrow chimeras was investigated. The combination of C57Bl mice as bone marrow donors and CBA/CA mice as irradiated recipients (800 rad) was used because of their strong histoincompatibility on the H-2 loci. All allografted recipients received 10 X 10(6) bone marrow cells. The majority of the recipients, which were rendered gnotobiotic by an antimicrobial treatment, achieved stable long term chimerism. In contrast, the conventional chimeras died from secondary disease within 9 weeks after transplantation. As early as 14 days after allogeneic bone marrow grafting the gnotobiotic recipients tolerated the reassociation with a conventional microflora without a change in the rate of mortality. Bone marrow cells (8 X 10(6) i.v.) and spleen cells (2 X 10(6) i.v.) collected from allogeneic chimeras failed to induce graft-versus-host-reaction (GVH) in a second lethally irradiated host. The data indicate, that the high rate of mortality in murine allogeneic bone marrow chimeras results from delayed GVH-reaction and systemic infection. The marrow graft, once established seems to exert tolerance against the allogeneic host. The pathogenesis of the systemic infection has not yet been worked out. It is assumed that it originates from bacteremia, induced by radiation dependent lesions of the epithelial integrity and defected lymphatic tissue in the gut.", "contents": "Allogeneic bone marrow transplantation in conventional mice: I. Effect of antibiotic therapy on long term survival of allogeneic chimeras. In the present communication the beneficial effect of long term antimicrobial treatment with poorly absorbable antiboitics on the survival of allogeneic bone marrow chimeras was investigated. The combination of C57Bl mice as bone marrow donors and CBA/CA mice as irradiated recipients (800 rad) was used because of their strong histoincompatibility on the H-2 loci. All allografted recipients received 10 X 10(6) bone marrow cells. The majority of the recipients, which were rendered gnotobiotic by an antimicrobial treatment, achieved stable long term chimerism. In contrast, the conventional chimeras died from secondary disease within 9 weeks after transplantation. As early as 14 days after allogeneic bone marrow grafting the gnotobiotic recipients tolerated the reassociation with a conventional microflora without a change in the rate of mortality. Bone marrow cells (8 X 10(6) i.v.) and spleen cells (2 X 10(6) i.v.) collected from allogeneic chimeras failed to induce graft-versus-host-reaction (GVH) in a second lethally irradiated host. The data indicate, that the high rate of mortality in murine allogeneic bone marrow chimeras results from delayed GVH-reaction and systemic infection. The marrow graft, once established seems to exert tolerance against the allogeneic host. The pathogenesis of the systemic infection has not yet been worked out. It is assumed that it originates from bacteremia, induced by radiation dependent lesions of the epithelial integrity and defected lymphatic tissue in the gut."}
{"id": "PMID:20187", "title": "Acid-base response to chronic hypocapnia in man.", "content": "The acid-base values of 13 patients with stable carbon dioxide tensions under controlled ventilation have been used to define the response to chronic hypocapnia in man. These patients had a respiratory paralysis and no apparent complicating disorders. Over a range of carbon dioxide tensions from 24 to 40 millimetres of mercury, the arterial blood hydrogen ion concentration decreased linearly by 0.32 nanomole per litre per millimetre of mercury decrement in carbon dioxide tension. Of primary interest was the finding that the slope of the regression line in chronic hypocapnia is close to that already reported for chronic hypercapnia. The physiological response to chronic hypocapnia in man is defined by a band that is approximately 10 nanomoles per litre (0.09 pH unit) wide for hydrogen ion concentration and 6 millimoles per litre wide for bicarbonate concentration. These significance bands may be used to differentiate additional acid-base disorders in patients with chronic hypocapnia over a clinically useful range of carbon dioxide tensions.", "contents": "Acid-base response to chronic hypocapnia in man. The acid-base values of 13 patients with stable carbon dioxide tensions under controlled ventilation have been used to define the response to chronic hypocapnia in man. These patients had a respiratory paralysis and no apparent complicating disorders. Over a range of carbon dioxide tensions from 24 to 40 millimetres of mercury, the arterial blood hydrogen ion concentration decreased linearly by 0.32 nanomole per litre per millimetre of mercury decrement in carbon dioxide tension. Of primary interest was the finding that the slope of the regression line in chronic hypocapnia is close to that already reported for chronic hypercapnia. The physiological response to chronic hypocapnia in man is defined by a band that is approximately 10 nanomoles per litre (0.09 pH unit) wide for hydrogen ion concentration and 6 millimoles per litre wide for bicarbonate concentration. These significance bands may be used to differentiate additional acid-base disorders in patients with chronic hypocapnia over a clinically useful range of carbon dioxide tensions."}
{"id": "PMID:20191", "title": "Effects of aspirin-like drugs on canine gastric mucosal blood flow and acid secretion.", "content": "1. The effects of aspirin, paracetamol and benorylate were studied on gastric mucosal blood flow (MBF) and acid secretion in canine denervated gastric pouches. 2. Aspirin 20 mM in the unstimulated pouch had no effect; pentagastrin-stimulated acid output, but not MBF, was reduced. Aspirin buffered to pH 6 was ineffective. 3. Aspirin 3-50 mg/kg reaching the pentagastrin-stimulated pouch through the blood, increased acid secretion and MBF, but the MBF:secretion ratio was variably affected. 4. Paracetamol (10 or 20 mg/kg i.v., or 20 mM in the pouch) or benorylate (280 mg/kg orally) mainly had little effect. 5. Circular muscle strips from dog arteries were contracted by prostaglandins E2, F1alpha or F2alpha, and often slightly by indomethacine, but prostaglandin E1 produced variable effects. 6. These results do not favour the view that aspirin causes gastric bleeding in dogs by breakdown of blood vessels due to ischaemia following mucosal vasoconstriction.", "contents": "Effects of aspirin-like drugs on canine gastric mucosal blood flow and acid secretion. 1. The effects of aspirin, paracetamol and benorylate were studied on gastric mucosal blood flow (MBF) and acid secretion in canine denervated gastric pouches. 2. Aspirin 20 mM in the unstimulated pouch had no effect; pentagastrin-stimulated acid output, but not MBF, was reduced. Aspirin buffered to pH 6 was ineffective. 3. Aspirin 3-50 mg/kg reaching the pentagastrin-stimulated pouch through the blood, increased acid secretion and MBF, but the MBF:secretion ratio was variably affected. 4. Paracetamol (10 or 20 mg/kg i.v., or 20 mM in the pouch) or benorylate (280 mg/kg orally) mainly had little effect. 5. Circular muscle strips from dog arteries were contracted by prostaglandins E2, F1alpha or F2alpha, and often slightly by indomethacine, but prostaglandin E1 produced variable effects. 6. These results do not favour the view that aspirin causes gastric bleeding in dogs by breakdown of blood vessels due to ischaemia following mucosal vasoconstriction."}
{"id": "PMID:20192", "title": "The uptake and overflow of radiolabelled beta-adrenoceptor blocking agents by the isolated vas deferens of the rat.", "content": "1. A comparison of uptake into and overflow from the isolated vas deferens of the rat has been made between [3H]-noradrenaline ([3H]-NA), [14C]-D-sorbitol and three radio-labelled beta-adrenoceptor blocking agents, [14C]-practolol, [14C]-(+/-)-propranolol and [3H]-penbutolol. 2. The accumulation of [3H]-NA after 30 min incubation was reduced by desmethylimipramine (DMI) 1 X 10(-8)M and was also reduced in vasa from rats pretreated with 6-hydroxydopamine (6-OHDA). This was not so with [14C]-D-sorbitol. 3. 6-OHDA pretreatment of the rats reduced the uptake of [3H]-penbutolol after 30 min incubation but not that of [4C]-propranolol or [14C]-practolol. DMI 1 X 10(-8)M did not alter the tissue uptake of [14C]-propranolol, [14C]-practolol or [3H]-penbutolol. 4. Electrical stimulation of vasa preloaded with [3H]-NA caused a significantly greater increase in [3H]-NA overflow than during the resting, unstimulated periods. No such increase in overflow was observed with [14C]-sorbitol or any of the three beta-adrenoceptor blocking agents use. 5. The beta-adrenoceptor blocking agent penbutolol was shown to possess adrenergic neurone blocking activity in the isolated vas deferens of the rat. 6. It is concluded that any effect that practolol or (+/-)-propranolol have on noradrenergic neurones is brought about without the need for these drugs to gain access to the interior of the neurone.", "contents": "The uptake and overflow of radiolabelled beta-adrenoceptor blocking agents by the isolated vas deferens of the rat. 1. A comparison of uptake into and overflow from the isolated vas deferens of the rat has been made between [3H]-noradrenaline ([3H]-NA), [14C]-D-sorbitol and three radio-labelled beta-adrenoceptor blocking agents, [14C]-practolol, [14C]-(+/-)-propranolol and [3H]-penbutolol. 2. The accumulation of [3H]-NA after 30 min incubation was reduced by desmethylimipramine (DMI) 1 X 10(-8)M and was also reduced in vasa from rats pretreated with 6-hydroxydopamine (6-OHDA). This was not so with [14C]-D-sorbitol. 3. 6-OHDA pretreatment of the rats reduced the uptake of [3H]-penbutolol after 30 min incubation but not that of [4C]-propranolol or [14C]-practolol. DMI 1 X 10(-8)M did not alter the tissue uptake of [14C]-propranolol, [14C]-practolol or [3H]-penbutolol. 4. Electrical stimulation of vasa preloaded with [3H]-NA caused a significantly greater increase in [3H]-NA overflow than during the resting, unstimulated periods. No such increase in overflow was observed with [14C]-sorbitol or any of the three beta-adrenoceptor blocking agents use. 5. The beta-adrenoceptor blocking agent penbutolol was shown to possess adrenergic neurone blocking activity in the isolated vas deferens of the rat. 6. It is concluded that any effect that practolol or (+/-)-propranolol have on noradrenergic neurones is brought about without the need for these drugs to gain access to the interior of the neurone."}
{"id": "PMID:20194", "title": "Selective induction of tyrosine hydroxylase and dopamine beta-hydroxylase by nerve growth factor: comparison between adrenal medulla and sympathetic ganglia of adult and newborn rats.", "content": "Administration of NGF to newborn and adult rats elicits a selective increase in TH and DBH both in sympathetic ganglia and adrenal medulla. This effect does not depend on intact preganglionic cholinergic fibers. The augmented enzyme activity results from enhanced enzyme synthesis since it can be abolished by cycloheximide and NGF has been shown to enhance the incorporation of [3H]leucine into DBH molecules. The responsiveness of the adrenal medulla to NGF is also supported by light and electron microscopic autoradiograms which show that intravenously injected 125I-NGF is accumulated with high selectivity in adrenal chromaffin as compared to adjacent adrenal cortical cells. In spite of the many similarities between the response of the adrenergic neurons and adrenal chromaffin cells to NGF, there are also two distinct differences. (a) In newborn rats the ratio between the TH increase effected by a single and 10 subsequent daily injections of NGF is 1:2 in the adrenal medulla and 1:7 in the superior cervical ganglia. (b) If adrenal medullae are transferred to organ culture after intravenous injection of NGF, maximal TH response is initiated 60-90 min after NGF administration. In superior cervical ganglia only a half-maximal response is initiated at that time. After a stationary phase a second increase starts after about 6 h to reach the maximum after 12 h. The biphasic time course of the initiation of TH induction by NGF in sympathetic ganglia is in agreement with the time course of 125I-NGF accumulation after intravenous injection27 reflecting the moiety of NGF reaching the cell bodies of the adrenergic neurons directly by the blood stream (initial accumulation) and by retrograde axonal transport (second phase).", "contents": "Selective induction of tyrosine hydroxylase and dopamine beta-hydroxylase by nerve growth factor: comparison between adrenal medulla and sympathetic ganglia of adult and newborn rats. Administration of NGF to newborn and adult rats elicits a selective increase in TH and DBH both in sympathetic ganglia and adrenal medulla. This effect does not depend on intact preganglionic cholinergic fibers. The augmented enzyme activity results from enhanced enzyme synthesis since it can be abolished by cycloheximide and NGF has been shown to enhance the incorporation of [3H]leucine into DBH molecules. The responsiveness of the adrenal medulla to NGF is also supported by light and electron microscopic autoradiograms which show that intravenously injected 125I-NGF is accumulated with high selectivity in adrenal chromaffin as compared to adjacent adrenal cortical cells. In spite of the many similarities between the response of the adrenergic neurons and adrenal chromaffin cells to NGF, there are also two distinct differences. (a) In newborn rats the ratio between the TH increase effected by a single and 10 subsequent daily injections of NGF is 1:2 in the adrenal medulla and 1:7 in the superior cervical ganglia. (b) If adrenal medullae are transferred to organ culture after intravenous injection of NGF, maximal TH response is initiated 60-90 min after NGF administration. In superior cervical ganglia only a half-maximal response is initiated at that time. After a stationary phase a second increase starts after about 6 h to reach the maximum after 12 h. The biphasic time course of the initiation of TH induction by NGF in sympathetic ganglia is in agreement with the time course of 125I-NGF accumulation after intravenous injection27 reflecting the moiety of NGF reaching the cell bodies of the adrenergic neurons directly by the blood stream (initial accumulation) and by retrograde axonal transport (second phase)."}
{"id": "PMID:20195", "title": "Biochemical differentiation of aggregating cell cultures of different fetal rat brain regions.", "content": "Rotation-mediated aggregating cell cultures of mechanically dissociated fetal rat brains divided into three (telencephalon, mesencephalon-diencephalon and rhombencephalon), or two (telencephalon and mesencephalon-diencephalon plus rhombencephalon) parts were examined for their biochemical differentiation by measuring the specific activities of choline acetyltransferase, acetylcholinesterase, glutamic acid decarboxylase, tyrosine 3-monooxygenase, aromatic L-amino acid decarboxylase, catechol methyltransferase and monoamine oxidase. The results showed that such parts yielded cultures that were relatively enriched for acetylcholine-synthesizing (telencephalon) or catecholamine-synthesizing (mesencephalon-diencephalon and mesencephalon-diencephalon plus rhombencephalon) enzymes. For cultures which were derived from two brain divisions, the sum of the total activity for each enzyme in the parts after 30 days equalled that in whole brain cultures derived from the same group of embryos, suggesting that development of these enzymes was unaffected by division of the brain in two. In experiments to determine the effects of culture conditions on this development, chronic administration of certain drugs was found to selectively influence the specific activity of certain neurotransmitter metabolizing enzymes. Thus, in cultures of whole brain, ascorbic acid (0.2 mM) decreased tyrosine 3-monooxygenase and aromatic L-amino acid decarboxylase while other enzymes were slightly increased; and in cultures of telencephalon and mesencephalon-diencephalon plus rhombencephalon, N6, O2'-dibutyryladenosine 3',5'-cyclic phosphate (0.2 mM) decreased the specific activities of choline acetyltransferase acetylcholinesterase, glutamic acid decarboxylase and monoamine oxidase. These results demonstrate the feasibility of growing these cultures for pharmacological studies in developmental neurobiology.", "contents": "Biochemical differentiation of aggregating cell cultures of different fetal rat brain regions. Rotation-mediated aggregating cell cultures of mechanically dissociated fetal rat brains divided into three (telencephalon, mesencephalon-diencephalon and rhombencephalon), or two (telencephalon and mesencephalon-diencephalon plus rhombencephalon) parts were examined for their biochemical differentiation by measuring the specific activities of choline acetyltransferase, acetylcholinesterase, glutamic acid decarboxylase, tyrosine 3-monooxygenase, aromatic L-amino acid decarboxylase, catechol methyltransferase and monoamine oxidase. The results showed that such parts yielded cultures that were relatively enriched for acetylcholine-synthesizing (telencephalon) or catecholamine-synthesizing (mesencephalon-diencephalon and mesencephalon-diencephalon plus rhombencephalon) enzymes. For cultures which were derived from two brain divisions, the sum of the total activity for each enzyme in the parts after 30 days equalled that in whole brain cultures derived from the same group of embryos, suggesting that development of these enzymes was unaffected by division of the brain in two. In experiments to determine the effects of culture conditions on this development, chronic administration of certain drugs was found to selectively influence the specific activity of certain neurotransmitter metabolizing enzymes. Thus, in cultures of whole brain, ascorbic acid (0.2 mM) decreased tyrosine 3-monooxygenase and aromatic L-amino acid decarboxylase while other enzymes were slightly increased; and in cultures of telencephalon and mesencephalon-diencephalon plus rhombencephalon, N6, O2'-dibutyryladenosine 3',5'-cyclic phosphate (0.2 mM) decreased the specific activities of choline acetyltransferase acetylcholinesterase, glutamic acid decarboxylase and monoamine oxidase. These results demonstrate the feasibility of growing these cultures for pharmacological studies in developmental neurobiology."}
{"id": "PMID:20197", "title": "The importance of Lactobacilli in maintaining normal microbial balance in the crop.", "content": "1. The effect of lactobacilli on Escherichia coli has been examined in vitro and in chicken crop in vivo. 2. Inhibition of E. coli was dependent on the presence of sufficient numbers of lactobacilli. 3. In a standard test some lactobacilli were bacteriostatic and one was bactericidal. The bacteriostasis was due to the low pH produced by these strains but bactericidal activity could not be accounted for by pH alone. 4. In gnotobiotic animals the bactericidal strain was no more inhibitory for E. coli than was a bacteriostatic strain.", "contents": "The importance of Lactobacilli in maintaining normal microbial balance in the crop. 1. The effect of lactobacilli on Escherichia coli has been examined in vitro and in chicken crop in vivo. 2. Inhibition of E. coli was dependent on the presence of sufficient numbers of lactobacilli. 3. In a standard test some lactobacilli were bacteriostatic and one was bactericidal. The bacteriostasis was due to the low pH produced by these strains but bactericidal activity could not be accounted for by pH alone. 4. In gnotobiotic animals the bactericidal strain was no more inhibitory for E. coli than was a bacteriostatic strain."}
{"id": "PMID:20198", "title": "[Actions of sodium dichloroacetate in combination with insulin on hyperlactatemia and hyperpyruvicemia induced in dogs by phenformin].", "content": "In the normal anesthetized dog the combination of insulin, whether of exogenous or endogenous origin, with sodium dichloroacetate provoke a rapid and important reduction of the hyperlactatemia and hyperpyruvicemia induced by the intraduodenal injection of high doses of phenformin. Furthermore this combination prevents the progressive and important lowering of the arterial pH provoked by phenformin.", "contents": "[Actions of sodium dichloroacetate in combination with insulin on hyperlactatemia and hyperpyruvicemia induced in dogs by phenformin]. In the normal anesthetized dog the combination of insulin, whether of exogenous or endogenous origin, with sodium dichloroacetate provoke a rapid and important reduction of the hyperlactatemia and hyperpyruvicemia induced by the intraduodenal injection of high doses of phenformin. Furthermore this combination prevents the progressive and important lowering of the arterial pH provoked by phenformin."}
{"id": "PMID:20199", "title": "[Effects of a beta-adrenolytic and a diuretic vis-\u00e0-vis hyper-reninemia induced by isoprenaline in anesthetized dogs. Value of beta blocking-diuretic interaction].", "content": "Intravenous injection of isoproterenol increases plasma renin activity (PRA) in anesthetized dogs. S. 464, a new beta adrenergic blocking agent, injected five minutes before isoproterenol, inhibits plasma renin hyperactivity. On the other hand, teclothiazide, a thiazide diuretic, induces no significant modification of the isoproterenol-induced increase of PRA. The combination of both compounds (five parts of S. 464, one part of diuretic), assumes the same inhibitory effects as S. 464 alone. These results and other experimental data (antihypertensive and diuretic activities) are discussed and explain the interest of such an association as a rational therapy of arterial hypertensive disorders.", "contents": "[Effects of a beta-adrenolytic and a diuretic vis-\u00e0-vis hyper-reninemia induced by isoprenaline in anesthetized dogs. Value of beta blocking-diuretic interaction]. Intravenous injection of isoproterenol increases plasma renin activity (PRA) in anesthetized dogs. S. 464, a new beta adrenergic blocking agent, injected five minutes before isoproterenol, inhibits plasma renin hyperactivity. On the other hand, teclothiazide, a thiazide diuretic, induces no significant modification of the isoproterenol-induced increase of PRA. The combination of both compounds (five parts of S. 464, one part of diuretic), assumes the same inhibitory effects as S. 464 alone. These results and other experimental data (antihypertensive and diuretic activities) are discussed and explain the interest of such an association as a rational therapy of arterial hypertensive disorders."}
{"id": "PMID:20200", "title": "[Action of 3-beta adrenolytics on plasma renin activity measured by radioimmunology in genetically hypertensive rats].", "content": "Spontaneously hypertensive rats (SHR) have basal levels of plasma renin activity (PRA) lower than the ones observed in normal Sprague Dawley rats. Three beta blocking agents are orally administered to unanesthetized spontaneously hypertensive and normotensive rats. Propranolol and S 464 reduce PRA in spontaneously hypertensive and normotensive control rats. Pindolol do not lower PRA in normotensive rats but increases levels of PRA in spontaneously hypertensive rats. These results are discussed.", "contents": "[Action of 3-beta adrenolytics on plasma renin activity measured by radioimmunology in genetically hypertensive rats]. Spontaneously hypertensive rats (SHR) have basal levels of plasma renin activity (PRA) lower than the ones observed in normal Sprague Dawley rats. Three beta blocking agents are orally administered to unanesthetized spontaneously hypertensive and normotensive rats. Propranolol and S 464 reduce PRA in spontaneously hypertensive and normotensive control rats. Pindolol do not lower PRA in normotensive rats but increases levels of PRA in spontaneously hypertensive rats. These results are discussed."}
{"id": "PMID:20202", "title": "[Partial disorganization of the anaphasic segregation of chromosomes in plant cells: combined actions of griseofulvin, producer of pluripolar anaphases and 2 ipecac alkaloids, producers of floating pole anaphases].", "content": "Anaphasis may be slightly checked by various treatments which however result in a normal chromosomic separation. Griseofulvin exerts a direct though partial influence on the mitotic apparatus, which entails \"pluripolar anaphasis\"; on the other hand Ipecac alkalo\u00efds act indirectly and produce \"floating poles anaphases\". Treatments combining griseofulvin with cepheline or tubulosine show that there is never any synergy between the two processes. These results support our hypothesis that floating poles anaphases are not a sign of slight C-mitotic action but only come from a lag between the appearance/disappearance of microtubules and that of chromosomes during anaphasis.", "contents": "[Partial disorganization of the anaphasic segregation of chromosomes in plant cells: combined actions of griseofulvin, producer of pluripolar anaphases and 2 ipecac alkaloids, producers of floating pole anaphases]. Anaphasis may be slightly checked by various treatments which however result in a normal chromosomic separation. Griseofulvin exerts a direct though partial influence on the mitotic apparatus, which entails \"pluripolar anaphasis\"; on the other hand Ipecac alkalo\u00efds act indirectly and produce \"floating poles anaphases\". Treatments combining griseofulvin with cepheline or tubulosine show that there is never any synergy between the two processes. These results support our hypothesis that floating poles anaphases are not a sign of slight C-mitotic action but only come from a lag between the appearance/disappearance of microtubules and that of chromosomes during anaphasis."}
{"id": "PMID:20205", "title": "Peripheral vascular and cardiac effects of nitrous oxide in the bovine.", "content": "Peripheral vascular and myocardial effects of increasing concentrations of nitrous oxide (0 to 70 per cent) in oxygen were determined in 15 unanaesthetized calves before and after replacement in their natural heart (NH) with a pneumatically driven artificial heart (AH). Nitrous oxide produced concentration-related decreases in arterial and mixed venous pH and increases in minute ventilation and arterial and mixed venous carbon dioxide tensions in both NH and AH calves. Nitrous oxide resulted in significant increases in cardiac output, stroke volume and mean aortic, pulmonary artery and right atrial pressures in NH and AH calves, but did not significantly change systemic vascular resistance in either group of animals. Heart rate was increased in NH calves but was fixed in AH calves. Elevations in heart rate and cardiac output at nitrous oxide concentrations greater than 30 per cent and aortic pressure at 70 per cent nitrous oxide were significantly greater in NH than AH animals (P less than 0.05). These data demonstrate that nitrous oxide stimulates the cardiovascular system in spontaneously breathing mammals and that the changes result from improved venous return and an increase in myocardial chronotropy. Our findings also suggest that cardiovascular stimulation during nitrous oxide breathing may be related to increased concentrations of arterial and/or venous carbon dioxide.", "contents": "Peripheral vascular and cardiac effects of nitrous oxide in the bovine. Peripheral vascular and myocardial effects of increasing concentrations of nitrous oxide (0 to 70 per cent) in oxygen were determined in 15 unanaesthetized calves before and after replacement in their natural heart (NH) with a pneumatically driven artificial heart (AH). Nitrous oxide produced concentration-related decreases in arterial and mixed venous pH and increases in minute ventilation and arterial and mixed venous carbon dioxide tensions in both NH and AH calves. Nitrous oxide resulted in significant increases in cardiac output, stroke volume and mean aortic, pulmonary artery and right atrial pressures in NH and AH calves, but did not significantly change systemic vascular resistance in either group of animals. Heart rate was increased in NH calves but was fixed in AH calves. Elevations in heart rate and cardiac output at nitrous oxide concentrations greater than 30 per cent and aortic pressure at 70 per cent nitrous oxide were significantly greater in NH than AH animals (P less than 0.05). These data demonstrate that nitrous oxide stimulates the cardiovascular system in spontaneously breathing mammals and that the changes result from improved venous return and an increase in myocardial chronotropy. Our findings also suggest that cardiovascular stimulation during nitrous oxide breathing may be related to increased concentrations of arterial and/or venous carbon dioxide."}
{"id": "PMID:20206", "title": "Purification and partial characterization of an exo-beta-glucanase from the yeast Kluyveromyces aestaurii.", "content": "The intracellular-periplasmic exo-1,3-beta-glucanase (EC 3.2.1.58) has been extracted from the yeast Kluyveromyces aestuarii and purified to immunoelectrophoretic homogeneity by ion-exchange and gel-exclusion chromatography. The kinetic constants and activation energies for laminarin, p-nitrophenyl-beta-D-glucoside, and pustulan have been determined, along with the effect of pH. Evidence is presented indicating that the enzyme is composed of a single polypeptide chain, about 24% carbohydrates, and its molecular weight was estimated to be 43 000.", "contents": "Purification and partial characterization of an exo-beta-glucanase from the yeast Kluyveromyces aestaurii. The intracellular-periplasmic exo-1,3-beta-glucanase (EC 3.2.1.58) has been extracted from the yeast Kluyveromyces aestuarii and purified to immunoelectrophoretic homogeneity by ion-exchange and gel-exclusion chromatography. The kinetic constants and activation energies for laminarin, p-nitrophenyl-beta-D-glucoside, and pustulan have been determined, along with the effect of pH. Evidence is presented indicating that the enzyme is composed of a single polypeptide chain, about 24% carbohydrates, and its molecular weight was estimated to be 43 000."}
{"id": "PMID:20207", "title": "The role of divalent cations in the activation of the NADP+-specific isocitrate dehydrogenase from Pisum sativum L.", "content": "A divalent cation electrode was used to measure the stability constants (association constants) for the magnesium and manganese complexes of the substrates for the NADP+-specific isocitrate dehydrogenase (EC 1.1.1.42) from pea stems. At an ionic strength of 26.5 mM and at pH 7.4 the stability constants for the Mg2+-isocitrate and Mg2+-NADP+ complexes were 0.85 +/- 0.2 and 0.43 +/- 0.04 mM-1 respectively and for the Mn2+-isocitrate and Mn2+-NADP+ complexes they were 1.25 +/- 0.07 and 0.75 +/- 0.09 mM-1 respectively. At the same ionic strength but at pH 6.0 the Mg2+-NADPH and Mn2+-NADPH complexes had stability constants of 0.95 +/- 0.23 and 1.79 +/- 0.34 mM-1 respectively. Oxalosuccinate and alpha-ketoglutarate do not form measureable complexes under these conditions. Saturation kinetics of the enzyme with respect to isocitrate and metal ions are consistent with the metal-isocitrate complex being the substrate for the enzyme. NADP+ binds to the enzyme in the free form. Saturation kinetics of NADPH and Mn2+ indicate that the metal-NADPH complex is the substrate in the reverse reaction. In contrast the pig heart enzyme appears to bind free NADPH and Mn2+. A scheme for the reaction mechanism is presented and the difference between the reversibility of the NAD+ and NADP+ enzyme is discussed in relation to the stability of the NADH and NADPH metal complexes.", "contents": "The role of divalent cations in the activation of the NADP+-specific isocitrate dehydrogenase from Pisum sativum L. A divalent cation electrode was used to measure the stability constants (association constants) for the magnesium and manganese complexes of the substrates for the NADP+-specific isocitrate dehydrogenase (EC 1.1.1.42) from pea stems. At an ionic strength of 26.5 mM and at pH 7.4 the stability constants for the Mg2+-isocitrate and Mg2+-NADP+ complexes were 0.85 +/- 0.2 and 0.43 +/- 0.04 mM-1 respectively and for the Mn2+-isocitrate and Mn2+-NADP+ complexes they were 1.25 +/- 0.07 and 0.75 +/- 0.09 mM-1 respectively. At the same ionic strength but at pH 6.0 the Mg2+-NADPH and Mn2+-NADPH complexes had stability constants of 0.95 +/- 0.23 and 1.79 +/- 0.34 mM-1 respectively. Oxalosuccinate and alpha-ketoglutarate do not form measureable complexes under these conditions. Saturation kinetics of the enzyme with respect to isocitrate and metal ions are consistent with the metal-isocitrate complex being the substrate for the enzyme. NADP+ binds to the enzyme in the free form. Saturation kinetics of NADPH and Mn2+ indicate that the metal-NADPH complex is the substrate in the reverse reaction. In contrast the pig heart enzyme appears to bind free NADPH and Mn2+. A scheme for the reaction mechanism is presented and the difference between the reversibility of the NAD+ and NADP+ enzyme is discussed in relation to the stability of the NADH and NADPH metal complexes."}
{"id": "PMID:20208", "title": "The interaction of human glycophorin with 8-anilino-1-naphthalene sulfonate.", "content": "Both the sialoglycoprotein of human erythrocyte membranes, glycophorin, and the sialic acid free protein, obtained by treatment of glycophorin with neuraminidase (EC 3.2.1.18), increase the fluorescence of 8-anilino-1-naphthalene sulfonate (ANS). Binding of ANS to glycophorin is weak compared with the binding to bovine serum albumin (BSA). equilibrium dialysis gives an apparent binding constant of about 4 X 10(3) M(-1) at neutral pH, but Ka increases 1.75 times when NaCl or CaCl2 are added and 10-fold when the pH is lowered to 3.0. Sialic acid groups do not significantly affect ANS binding, although they have some effect at low ionic strength and neutral pH. Fluorescence studies indicate only one to two binding sites for ANS, with apparent pK = 3.8 +/- 0.2, and located close to aromatic residues in glycophorin. Polarization and quantum efficiency of the fluorescence of ANS associated with glycophorin fail to indicate changes in the vicinity of the binding site when the pH is lowered.", "contents": "The interaction of human glycophorin with 8-anilino-1-naphthalene sulfonate. Both the sialoglycoprotein of human erythrocyte membranes, glycophorin, and the sialic acid free protein, obtained by treatment of glycophorin with neuraminidase (EC 3.2.1.18), increase the fluorescence of 8-anilino-1-naphthalene sulfonate (ANS). Binding of ANS to glycophorin is weak compared with the binding to bovine serum albumin (BSA). equilibrium dialysis gives an apparent binding constant of about 4 X 10(3) M(-1) at neutral pH, but Ka increases 1.75 times when NaCl or CaCl2 are added and 10-fold when the pH is lowered to 3.0. Sialic acid groups do not significantly affect ANS binding, although they have some effect at low ionic strength and neutral pH. Fluorescence studies indicate only one to two binding sites for ANS, with apparent pK = 3.8 +/- 0.2, and located close to aromatic residues in glycophorin. Polarization and quantum efficiency of the fluorescence of ANS associated with glycophorin fail to indicate changes in the vicinity of the binding site when the pH is lowered."}
{"id": "PMID:20209", "title": "Purification and partial characterization of cysteine-glutamate transaminase from rat liver.", "content": "Cysteine-glutamate transaminase (cysteine aminotransferase; EC 2.6.1.3) has been purified 149-fold to an apparent homogeneity giving a specific activity of 2.09 IU per milligram of protein with an overall yield of 15%. The isolation procedures involve the preliminary separation of a crude rat liver homogenate which was submitted sequentially to ammonium sulfate fractionation, TEAE-cellulose column chromatography, ultrafiltration, and isoelectrofocusing. The final product was homogenous when examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). A minimal molecular weight of 83 500 was determined by Sephadex gel chromatography. The molecular weight as estimated by polyacrylamide gel electrophoresis in the presence of SDS was 84 000. The purified enzyme exhibited a pH optimum at 8.2 with cysteine and alpha-ketoglutarate as substrates. The enzyme is inactivated slowly when kept frozen and is completely inactivated if left at room temperature for 1 h. The enzyme does not catalyze the transamination of alpha-methyl-DL-cysteine, which, when present to a final concentration of 10 mM, exhibits a 23.2% inhibition of transamination of 30 mM of cysteine. The mechanism apparently resembles that of aspartate-glutamate transaminase (EC 2.6.1.1) in which the presence of a labile hydrogen on the alpha-carbon in the substrate is one of the strict requirements.", "contents": "Purification and partial characterization of cysteine-glutamate transaminase from rat liver. Cysteine-glutamate transaminase (cysteine aminotransferase; EC 2.6.1.3) has been purified 149-fold to an apparent homogeneity giving a specific activity of 2.09 IU per milligram of protein with an overall yield of 15%. The isolation procedures involve the preliminary separation of a crude rat liver homogenate which was submitted sequentially to ammonium sulfate fractionation, TEAE-cellulose column chromatography, ultrafiltration, and isoelectrofocusing. The final product was homogenous when examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). A minimal molecular weight of 83 500 was determined by Sephadex gel chromatography. The molecular weight as estimated by polyacrylamide gel electrophoresis in the presence of SDS was 84 000. The purified enzyme exhibited a pH optimum at 8.2 with cysteine and alpha-ketoglutarate as substrates. The enzyme is inactivated slowly when kept frozen and is completely inactivated if left at room temperature for 1 h. The enzyme does not catalyze the transamination of alpha-methyl-DL-cysteine, which, when present to a final concentration of 10 mM, exhibits a 23.2% inhibition of transamination of 30 mM of cysteine. The mechanism apparently resembles that of aspartate-glutamate transaminase (EC 2.6.1.1) in which the presence of a labile hydrogen on the alpha-carbon in the substrate is one of the strict requirements."}
{"id": "PMID:20210", "title": "Electrolyte levels and net fluid and electrolyte movements in the gastrointestinal tract of weanling swine.", "content": "Electrolyte concentrations, osmolality and pH were determined in conventionally raised weanling swine fed a liquid diet. Incorporation of a dilution marker into the diet in combination with frequent feeding enabled estimations as to the sites of relative fluid and electrolyte absorption and secretion along the gastrointestinal tract. Unlike many other species the weanling pig depends largely on its large intestine for absorption of fluid and electrolytes with small changes in net fluid movement occurring along the jejunal and ileal segments. Additional observations included the absorption of water by the porcine stomach which increased dilution marker concentration by approximately twofold and the high osmolality values recorded in the small and large intestine. The implications of these observations are discussed with regard to pathogenesis of colibacillary diarrhea in the weanling pig.", "contents": "Electrolyte levels and net fluid and electrolyte movements in the gastrointestinal tract of weanling swine. Electrolyte concentrations, osmolality and pH were determined in conventionally raised weanling swine fed a liquid diet. Incorporation of a dilution marker into the diet in combination with frequent feeding enabled estimations as to the sites of relative fluid and electrolyte absorption and secretion along the gastrointestinal tract. Unlike many other species the weanling pig depends largely on its large intestine for absorption of fluid and electrolytes with small changes in net fluid movement occurring along the jejunal and ileal segments. Additional observations included the absorption of water by the porcine stomach which increased dilution marker concentration by approximately twofold and the high osmolality values recorded in the small and large intestine. The implications of these observations are discussed with regard to pathogenesis of colibacillary diarrhea in the weanling pig."}
{"id": "PMID:20211", "title": "Studies on the antigenicity of an inactivated, aluminum hydroxide adjuvant equine influenza vaccine.", "content": "An inactivated, aluminum hydroxide adjuvant equine influenza vaccine was tested in horses and guinea pigs to determine the levels of antigen that would elicit maximum serological responses. Vaccine containing serial twofold increments of A/Equi-1/Prague and A/Equi-2/Miami strains of equine influenza virus was administered to random groupings of both types of test animals. The hemagglutination inhibition antibody response for each group was then measured. Results in horses and guinea pigs were compared to determine if the equine serological values could be related to a potency test in laboratory animals. The highest mean hemagglutination inhibition antibody response in horses occurred in groups vaccinated, respectively, with 128 or 256 hemagglutination units of A/Equi-1 and 512 or 1024 hemagglutination units of A/Equi-2 antigen. Groups vaccinated with further two- or fourfold increases in these antigens had mean hemagglutination inhibition titers that were somewhat lower than the maximum levels. When graded doses of vaccine were given to guinea pigs, their hemagglutination inhibition antibody titers reached a plateau of maximum values, similar to the serological response in vaccinated horses. Test horses remained clinically free from signs of equine influenza during the year following vaccination and no untoward post-vaccination reactions were observed.", "contents": "Studies on the antigenicity of an inactivated, aluminum hydroxide adjuvant equine influenza vaccine. An inactivated, aluminum hydroxide adjuvant equine influenza vaccine was tested in horses and guinea pigs to determine the levels of antigen that would elicit maximum serological responses. Vaccine containing serial twofold increments of A/Equi-1/Prague and A/Equi-2/Miami strains of equine influenza virus was administered to random groupings of both types of test animals. The hemagglutination inhibition antibody response for each group was then measured. Results in horses and guinea pigs were compared to determine if the equine serological values could be related to a potency test in laboratory animals. The highest mean hemagglutination inhibition antibody response in horses occurred in groups vaccinated, respectively, with 128 or 256 hemagglutination units of A/Equi-1 and 512 or 1024 hemagglutination units of A/Equi-2 antigen. Groups vaccinated with further two- or fourfold increases in these antigens had mean hemagglutination inhibition titers that were somewhat lower than the maximum levels. When graded doses of vaccine were given to guinea pigs, their hemagglutination inhibition antibody titers reached a plateau of maximum values, similar to the serological response in vaccinated horses. Test horses remained clinically free from signs of equine influenza during the year following vaccination and no untoward post-vaccination reactions were observed."}
{"id": "PMID:20212", "title": "Proximal-distal absorptive gradients in the in vivo intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats.", "content": "Using a single-pass perfusion technique, H2O, Na+, Cl-, HCO3-, and glucose absorption were studied in the jejunum and proximal and distal ileum of rats either uninfected or infected with a tapeworm parasite (Hymenolepis diminuta). The effect of parasitization, region of the intestine, type of buffer, and concentration of glucose in the perfusion fluids on the transport data were analyzed by univariate and multivariate techniques. Proximal-distal flux gradients were observed for water and all the solute species studied, as well as for glucose- and bicarbonate-stimulated salt and water transport; there was a decreasing sensitivity to low pH proceeding distally. The major regional differences occurred between the proximal and distal ileum, with the fluxes in the jejunum being similar to those in the proximal ileum. Na+, H2O, and glucose transport decreased, while Cl- absorption increased, proceeding distally. The parasites diminished the rates of absorption of glucose, salt, and water, and altered the flux gradients, particularly the Na+ and HCO3- transport gradients. The differences in the gradients between control and infected animals were related to differential sensitivity of the different transport systems in the various regions of the gut to parasitism.", "contents": "Proximal-distal absorptive gradients in the in vivo intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats. Using a single-pass perfusion technique, H2O, Na+, Cl-, HCO3-, and glucose absorption were studied in the jejunum and proximal and distal ileum of rats either uninfected or infected with a tapeworm parasite (Hymenolepis diminuta). The effect of parasitization, region of the intestine, type of buffer, and concentration of glucose in the perfusion fluids on the transport data were analyzed by univariate and multivariate techniques. Proximal-distal flux gradients were observed for water and all the solute species studied, as well as for glucose- and bicarbonate-stimulated salt and water transport; there was a decreasing sensitivity to low pH proceeding distally. The major regional differences occurred between the proximal and distal ileum, with the fluxes in the jejunum being similar to those in the proximal ileum. Na+, H2O, and glucose transport decreased, while Cl- absorption increased, proceeding distally. The parasites diminished the rates of absorption of glucose, salt, and water, and altered the flux gradients, particularly the Na+ and HCO3- transport gradients. The differences in the gradients between control and infected animals were related to differential sensitivity of the different transport systems in the various regions of the gut to parasitism."}
{"id": "PMID:20213", "title": "Influence of cold exposure and thyroid hormones on regulation of adrenal catecholamines.", "content": "Since thyroid hormones influence urinary excretion of catecholamines after exposure to cold, the effects of hyper- and hypo-thyroidism on adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2), phenylethanolamine-N-methyl transferase (PNMT) (EC 2.1.1.28), and serum dopamine-beta-hydroxylase (DbetaH) (EC 1.14.17.1) of rats of 23 and 4 degrees C were studied. TH changes resembled the urinary excretion pattern at 4 degrees C in being higher after 8 days than after 1 day of exposure, and in declining as acclimation occurred. At 23 degrees C, TH activity of hypothyroid rats was significantly higher than in euthyroid or hyperthyroid animals, and after 1 day at 4 degrees C the value increased even more. While in the hypothyroid animals at 4 degrees C the concentration of adrenal catecholamines was less, the epinephrine to norepinephrine ratio was higher than at 23 degrees C. Very high TH activity with a decline in catecholamine concentration suggests that the capacity of TH had been exceeded. PNMT activity was significantly elevated in this group. TH activity was not decreased in the hyperthyroid group at 23 degrees C, and was increased after 8 days at 4 degrees C, suggesting that circulating thyroid hormones have no direct inhibitory effect on TH. Serum DbetaH was elevated after exposure to 4 degrees C, regardless of thyroid hormonal status. The activation of adrenal TH in hypothyroid rats at 23 degrees C and of TH, PNMT, and serum DbetaH at 4 degrees C is probably the result of increased activity of the sympathetic nervous system.", "contents": "Influence of cold exposure and thyroid hormones on regulation of adrenal catecholamines. Since thyroid hormones influence urinary excretion of catecholamines after exposure to cold, the effects of hyper- and hypo-thyroidism on adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2), phenylethanolamine-N-methyl transferase (PNMT) (EC 2.1.1.28), and serum dopamine-beta-hydroxylase (DbetaH) (EC 1.14.17.1) of rats of 23 and 4 degrees C were studied. TH changes resembled the urinary excretion pattern at 4 degrees C in being higher after 8 days than after 1 day of exposure, and in declining as acclimation occurred. At 23 degrees C, TH activity of hypothyroid rats was significantly higher than in euthyroid or hyperthyroid animals, and after 1 day at 4 degrees C the value increased even more. While in the hypothyroid animals at 4 degrees C the concentration of adrenal catecholamines was less, the epinephrine to norepinephrine ratio was higher than at 23 degrees C. Very high TH activity with a decline in catecholamine concentration suggests that the capacity of TH had been exceeded. PNMT activity was significantly elevated in this group. TH activity was not decreased in the hyperthyroid group at 23 degrees C, and was increased after 8 days at 4 degrees C, suggesting that circulating thyroid hormones have no direct inhibitory effect on TH. Serum DbetaH was elevated after exposure to 4 degrees C, regardless of thyroid hormonal status. The activation of adrenal TH in hypothyroid rats at 23 degrees C and of TH, PNMT, and serum DbetaH at 4 degrees C is probably the result of increased activity of the sympathetic nervous system."}
{"id": "PMID:20216", "title": "The catabolism of L-tyrosine by an Arthrobacter sp.", "content": "An Arthrobacter sp. metabolizes L-tyrosine by a pathway involving 3,4-dihydroxyphenylacetate as a key intermediate. p-Hydroxyphenylpyruvate is formed from tyrosine by an amino-transferase specifically requiring alpha-ketoglutarate for activity, and is then converted to p-hydroxyphenylacetate by an oxidative decarboxylation. p-Hydroxyphenylacetaldehyde is not an intermediate in the formation of p-hydroxyphenylacetate. Extracts of the bacterium oxidize 3,4-dihydroxyphenylacetate to delta-carboxymethyl-alpha-hydroxymuconic acid which, when supplemented with 2 mol of diphosphopyridine dinucleotide, results in the production of stoichiometric amounts of succinate and pyruvate.", "contents": "The catabolism of L-tyrosine by an Arthrobacter sp. An Arthrobacter sp. metabolizes L-tyrosine by a pathway involving 3,4-dihydroxyphenylacetate as a key intermediate. p-Hydroxyphenylpyruvate is formed from tyrosine by an amino-transferase specifically requiring alpha-ketoglutarate for activity, and is then converted to p-hydroxyphenylacetate by an oxidative decarboxylation. p-Hydroxyphenylacetaldehyde is not an intermediate in the formation of p-hydroxyphenylacetate. Extracts of the bacterium oxidize 3,4-dihydroxyphenylacetate to delta-carboxymethyl-alpha-hydroxymuconic acid which, when supplemented with 2 mol of diphosphopyridine dinucleotide, results in the production of stoichiometric amounts of succinate and pyruvate."}
{"id": "PMID:20217", "title": "The cellulase system of a Cytophaga species.", "content": "Cellulases (EC 3.2.1.4) of a Cytophaga species WTHC 2421 (ATCC 29474) were found in the soluble portion of the cell (the periplasm and the cytoplasm) and on the membrane. Cell-free cellulases were not found. Most of the carboxymethylcellulase activity associated with reduction of viscosity was membrane bound, whereas most of the carboxymethylcellulose (CMC) saccharifying activity was soluble. The CMC-saccharifying activity was increased 534 X by purification procedures which included ammonium sulfate precipitation and molecular exclusion chromatography with Sephadex G-75 and Biogel p-100. Periplasmic carboxymethycellulase had a molecular weight of 6250 and cytoplasmic carboxymethylcellulase had a molecular weight of 8650. Analytical ultracentrifugation of the periplasmic carboxymethylcellulase (CMCase) indicated that it had a low molecular density. The chromatographic fraction containing periplasmic CMCase also contained enzyme activity against crystalline cellulose. The activity against crystalline cellulose was 238 X higher than the activity shown by the whole cell. The reaction of the enzyme with either CMC or dewaxed cotton produced only glucose. The enzyme was slightly inhibited by the presence of 0.01% (w/v) glucose, lactose, or cellobiose, but it was not affected by sucrose, and exhibited increased activity in the presence of xylose and fructose.", "contents": "The cellulase system of a Cytophaga species. Cellulases (EC 3.2.1.4) of a Cytophaga species WTHC 2421 (ATCC 29474) were found in the soluble portion of the cell (the periplasm and the cytoplasm) and on the membrane. Cell-free cellulases were not found. Most of the carboxymethylcellulase activity associated with reduction of viscosity was membrane bound, whereas most of the carboxymethylcellulose (CMC) saccharifying activity was soluble. The CMC-saccharifying activity was increased 534 X by purification procedures which included ammonium sulfate precipitation and molecular exclusion chromatography with Sephadex G-75 and Biogel p-100. Periplasmic carboxymethycellulase had a molecular weight of 6250 and cytoplasmic carboxymethylcellulase had a molecular weight of 8650. Analytical ultracentrifugation of the periplasmic carboxymethylcellulase (CMCase) indicated that it had a low molecular density. The chromatographic fraction containing periplasmic CMCase also contained enzyme activity against crystalline cellulose. The activity against crystalline cellulose was 238 X higher than the activity shown by the whole cell. The reaction of the enzyme with either CMC or dewaxed cotton produced only glucose. The enzyme was slightly inhibited by the presence of 0.01% (w/v) glucose, lactose, or cellobiose, but it was not affected by sucrose, and exhibited increased activity in the presence of xylose and fructose."}
{"id": "PMID:20218", "title": "The role of 6-phosphogluconate dehydrogenase in Rhizobium.", "content": "A nicotinamide adenine dinucleotide (NAD) linked 6-phosphogluconate (6-PG)dehydrogenase has been detected in Rhizobium. The enzyme activity is similar in both slow- and fast-growing rhizobia. The nicotinamide adenine dinucleotide phosphate (NADP) dependent 6-PG dehydrogenase was detected only in the fast growers and was more than twice as active as the NAD-linked enzyme. Partial characterization of the products of 6-PG oxidation in Rhizobium suggests that the NADP-linked enzyme is the decarboxylating enzyme of the pentose phosphate (PP) pathway (EC 1.1.1.44) whereas a phosphorylated six-carbon compound, containing ketonic group(s), is the product of the oxidation catalyzed by the NAD-linked enzyme.", "contents": "The role of 6-phosphogluconate dehydrogenase in Rhizobium. A nicotinamide adenine dinucleotide (NAD) linked 6-phosphogluconate (6-PG)dehydrogenase has been detected in Rhizobium. The enzyme activity is similar in both slow- and fast-growing rhizobia. The nicotinamide adenine dinucleotide phosphate (NADP) dependent 6-PG dehydrogenase was detected only in the fast growers and was more than twice as active as the NAD-linked enzyme. Partial characterization of the products of 6-PG oxidation in Rhizobium suggests that the NADP-linked enzyme is the decarboxylating enzyme of the pentose phosphate (PP) pathway (EC 1.1.1.44) whereas a phosphorylated six-carbon compound, containing ketonic group(s), is the product of the oxidation catalyzed by the NAD-linked enzyme."}
{"id": "PMID:20219", "title": "Glycogen synthesis by amylosucrase from Neisseria perflava.", "content": "Amylosucrase (sucrose:1,4-alpha-D-glucan 4-alpha-glucosyltransferase; EC 2.4.1.4) which mediates the transfer of the glucosyl moiety of sucrose to a growing alpha-1,4-glucan chain is a constitutive enzyme of Neisseria perflava. The products of enzymic action are insoluble glycogenlike polysaccharides and fructose, the latter being a competitive inhibitor of the enzyme (Ki=20 mM). The enzyme is extremely stable and appears to bind very tightly to its polymerized product. Properties of product-bound enzyme reflect those of the native complex.", "contents": "Glycogen synthesis by amylosucrase from Neisseria perflava. Amylosucrase (sucrose:1,4-alpha-D-glucan 4-alpha-glucosyltransferase; EC 2.4.1.4) which mediates the transfer of the glucosyl moiety of sucrose to a growing alpha-1,4-glucan chain is a constitutive enzyme of Neisseria perflava. The products of enzymic action are insoluble glycogenlike polysaccharides and fructose, the latter being a competitive inhibitor of the enzyme (Ki=20 mM). The enzyme is extremely stable and appears to bind very tightly to its polymerized product. Properties of product-bound enzyme reflect those of the native complex."}
{"id": "PMID:20223", "title": "Further development of a successful protocol of graft versus leukemia without fatal graft-versus-host disease in AKR mice.", "content": "We previously reported a successful model for treatment of BW 5147 leukemia in AKR mice by adoptive immunotherapy using allogeneic spleen cells from C57BL/6 mice. The leukemia cells were given 3 days before initiation of therapy. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA), followed by cyclophosphamide and syngeneic spleen cells. We now show that it is not necessary to use syngeneic spleen cells in the final transplant since H-2-compatible, allogeneic CBA cells are as effective. In addition, it is possible to initiate successful therapy 5 days after leukemia implantation providing that the initial cyclophosphamide, given in two doses of 100 mg/kg each and spaced 7 days apart, is administered prior to establishment of graft-versus-host reaction. Higher single doses of drugs were followed by fatal graft-versus-host disease.", "contents": "Further development of a successful protocol of graft versus leukemia without fatal graft-versus-host disease in AKR mice. We previously reported a successful model for treatment of BW 5147 leukemia in AKR mice by adoptive immunotherapy using allogeneic spleen cells from C57BL/6 mice. The leukemia cells were given 3 days before initiation of therapy. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA), followed by cyclophosphamide and syngeneic spleen cells. We now show that it is not necessary to use syngeneic spleen cells in the final transplant since H-2-compatible, allogeneic CBA cells are as effective. In addition, it is possible to initiate successful therapy 5 days after leukemia implantation providing that the initial cyclophosphamide, given in two doses of 100 mg/kg each and spaced 7 days apart, is administered prior to establishment of graft-versus-host reaction. Higher single doses of drugs were followed by fatal graft-versus-host disease."}
{"id": "PMID:20226", "title": "Glucocorticoid receptors in Morris hepatomas and host liver and the correlation of biological activity with receptor levels.", "content": "Glucocorticoid-binding macromolecules were examined in Morris hepatomas 7787, 5123tc, 3683F, 7800, and 3683 and the Reuber hepatoma H-35 with the use of the synthetic glucocorticoid, triamcinolone acetonide. The physical properties of the triamcinolone acetonide-binding macromolecules of the hepatomas indicate that they are specific glucocorticoid receptors. The equilibrium association constants (Ka), sedimentation coefficients, and sensitivity to sulfhydryl-blocking reagents were found to be similar when hepatoma receptors were compared with the known properties of the liver receptor. Probably the most convincing criterion that the triamcinolone acetonide-binding macromolecules from the hepatomas are specific receptors is that 50 to 90% of the receptor can be depleted from hepatoma cytosol by treating rats with cortisol. In adrenalectomized tumor-bearing rats, the receptor levels in hepatomas 7787, 7800, 5123tc, and H-35 are comparable to or greater than receptor levels of host liver. However, tryptophan oxygenase was not responsive to glucocorticoids in hepatoma 7800 although receptor levels were quite high, and there were no indications that the receptor molecules were altered. Hepatomas 3683 and 3686F have low levels of receptor which may be related to resistance of these tumors to glucocorticoid treatment.", "contents": "Glucocorticoid receptors in Morris hepatomas and host liver and the correlation of biological activity with receptor levels. Glucocorticoid-binding macromolecules were examined in Morris hepatomas 7787, 5123tc, 3683F, 7800, and 3683 and the Reuber hepatoma H-35 with the use of the synthetic glucocorticoid, triamcinolone acetonide. The physical properties of the triamcinolone acetonide-binding macromolecules of the hepatomas indicate that they are specific glucocorticoid receptors. The equilibrium association constants (Ka), sedimentation coefficients, and sensitivity to sulfhydryl-blocking reagents were found to be similar when hepatoma receptors were compared with the known properties of the liver receptor. Probably the most convincing criterion that the triamcinolone acetonide-binding macromolecules from the hepatomas are specific receptors is that 50 to 90% of the receptor can be depleted from hepatoma cytosol by treating rats with cortisol. In adrenalectomized tumor-bearing rats, the receptor levels in hepatomas 7787, 7800, 5123tc, and H-35 are comparable to or greater than receptor levels of host liver. However, tryptophan oxygenase was not responsive to glucocorticoids in hepatoma 7800 although receptor levels were quite high, and there were no indications that the receptor molecules were altered. Hepatomas 3683 and 3686F have low levels of receptor which may be related to resistance of these tumors to glucocorticoid treatment."}
{"id": "PMID:20227", "title": "Production of calcitonin, adrenocorticotropic hormone, and beta-melanocyte-stimulating hormone in tumors derived from amine precursor uptake and decarboxylation cells.", "content": "The tumor production of human calcitonin (CT) was examined by radioimmunoassay, and it was found that 50 of 85 (59%) tumor tissues collected at random contained immunoreactive CT. These tumors were grouped as to whether they were derived from the amine precursor uptake and decarboxylation (APUD) series. The group that was derived from APUD cells showed appreciable amounts of CT in 30 of 31 (97%) of these tumors or in 20 of 21 (95%) when the medullary carcinomas of the thyroid were excluded. However, of the non-APUD group of tumors only 20 of 54 (37%) were found to contain CT, so that the difference between these two groups was highly significant (p less than 0.001). Of the tumors with ectopic adrenocorticotropic hormone-melanocyte-stimulating hormone production, 12 of 14 were shown to contain CT. These data indicate that CT is a common product of the APUD tumors and that tumor production of CT is often associated with that of adrenocorticotropic hormone and beta-melanocyte-stimulating hormone.", "contents": "Production of calcitonin, adrenocorticotropic hormone, and beta-melanocyte-stimulating hormone in tumors derived from amine precursor uptake and decarboxylation cells. The tumor production of human calcitonin (CT) was examined by radioimmunoassay, and it was found that 50 of 85 (59%) tumor tissues collected at random contained immunoreactive CT. These tumors were grouped as to whether they were derived from the amine precursor uptake and decarboxylation (APUD) series. The group that was derived from APUD cells showed appreciable amounts of CT in 30 of 31 (97%) of these tumors or in 20 of 21 (95%) when the medullary carcinomas of the thyroid were excluded. However, of the non-APUD group of tumors only 20 of 54 (37%) were found to contain CT, so that the difference between these two groups was highly significant (p less than 0.001). Of the tumors with ectopic adrenocorticotropic hormone-melanocyte-stimulating hormone production, 12 of 14 were shown to contain CT. These data indicate that CT is a common product of the APUD tumors and that tumor production of CT is often associated with that of adrenocorticotropic hormone and beta-melanocyte-stimulating hormone."}
{"id": "PMID:20228", "title": "The use of titanium (IV) oxide for the immobilisation of carbohydrate-directed enzymes.", "content": "The use of particles of porous titanium (IV) oxide as a suitable matrix for enzyme immobilisation has been investigated with dextranase. Treatment of the particles with enzyme in the presence and absence of ammonium ions showed that the presence of ammonia induced a greater coupling of protein, whereas a greater retention of enzyme specific activity was achieved in the absence of ammonia. Properties of the immobilised enzyme include a pH-dependence and reversibility of the coupling between enzyme and matrix. The immobilised dextranase was most stable at pH 5.0. Automated analytical techniques for measuring the activity of dextranase and other polysaccharidases in soluble and insoluble forms are also reported.", "contents": "The use of titanium (IV) oxide for the immobilisation of carbohydrate-directed enzymes. The use of particles of porous titanium (IV) oxide as a suitable matrix for enzyme immobilisation has been investigated with dextranase. Treatment of the particles with enzyme in the presence and absence of ammonium ions showed that the presence of ammonia induced a greater coupling of protein, whereas a greater retention of enzyme specific activity was achieved in the absence of ammonia. Properties of the immobilised enzyme include a pH-dependence and reversibility of the coupling between enzyme and matrix. The immobilised dextranase was most stable at pH 5.0. Automated analytical techniques for measuring the activity of dextranase and other polysaccharidases in soluble and insoluble forms are also reported."}
{"id": "PMID:20239", "title": "[Regulation and electric excitation of enzyme membranes in vitro].", "content": "Enzyme membranes can be activated or inhibited by applying continuous or alternating electrical fields. The field can modify the transport or reaction term of the transport-reaction by action on the displacement of charged species including those giving pH effects or inducing volume flows. A first experimental example is given: the progressive supression of the inhibition of hexokinase by the product when increasing alternating fields are applied. In the same way the apparent optimal pH approaches that of the soluble enzyme. In addition to its theoretical and practical implications electrical regulation can lead to the monitoring of enzyme reaction-driven mechanochemical fibers.", "contents": "[Regulation and electric excitation of enzyme membranes in vitro]. Enzyme membranes can be activated or inhibited by applying continuous or alternating electrical fields. The field can modify the transport or reaction term of the transport-reaction by action on the displacement of charged species including those giving pH effects or inducing volume flows. A first experimental example is given: the progressive supression of the inhibition of hexokinase by the product when increasing alternating fields are applied. In the same way the apparent optimal pH approaches that of the soluble enzyme. In addition to its theoretical and practical implications electrical regulation can lead to the monitoring of enzyme reaction-driven mechanochemical fibers."}
{"id": "PMID:20246", "title": "A kinetic spectrophotometric assay for rapid determination of acetoacetate in blood.", "content": "We describe an automated kinetic assay for acetoacetate in blood. Acetoacetate is enzymatically reduced to D-beta-hydroxybutyrate and the reaction is monitored for 60 s with a reaction-rate analyzer. This technique allows low concentrations of acetoacetate to be measured with good precision and overcomes many of the problems associated with other automated techniques. Our studies on the stability of acetoacetate emphasize the need for care in handling specimens. The use of a reaction-rate analyzer, an item of equipment common to most laboratories, allows for rapid handling of samples in small or large batches, depending on the needs of the laboratory.", "contents": "A kinetic spectrophotometric assay for rapid determination of acetoacetate in blood. We describe an automated kinetic assay for acetoacetate in blood. Acetoacetate is enzymatically reduced to D-beta-hydroxybutyrate and the reaction is monitored for 60 s with a reaction-rate analyzer. This technique allows low concentrations of acetoacetate to be measured with good precision and overcomes many of the problems associated with other automated techniques. Our studies on the stability of acetoacetate emphasize the need for care in handling specimens. The use of a reaction-rate analyzer, an item of equipment common to most laboratories, allows for rapid handling of samples in small or large batches, depending on the needs of the laboratory."}
{"id": "PMID:20247", "title": "Automated kinetic determination of lactate dehydrogenase isoenzymes in serum.", "content": "A steady-state kinetic method has been revised for measuring lactate dehydrogenase isoenzyme activities, which relates the inhibition of heart-type isoenzyme activity to the overall isoenzyme composition of the enzyme subunits. The method depends on the pH-dependent formation of an inhibitory ternary complex by the heart-type isoenzyme with NAD+ and pyruvate (if the reaction is measured by NADH oxidation). A preincubation step in the previous method is eliminated. The isoenzymes are measured by measuring the reduction of pyruvate in two different concentrations, which favor either the total or fractional activity, depending on the concentrations of pyruvate and the percentage of heart-type subunits. The method has been adapted to a centrifugal analyzer, which has speeded automated isoenzyme determinations, with an accuracy comparable to that for electrophoretic methods.", "contents": "Automated kinetic determination of lactate dehydrogenase isoenzymes in serum. A steady-state kinetic method has been revised for measuring lactate dehydrogenase isoenzyme activities, which relates the inhibition of heart-type isoenzyme activity to the overall isoenzyme composition of the enzyme subunits. The method depends on the pH-dependent formation of an inhibitory ternary complex by the heart-type isoenzyme with NAD+ and pyruvate (if the reaction is measured by NADH oxidation). A preincubation step in the previous method is eliminated. The isoenzymes are measured by measuring the reduction of pyruvate in two different concentrations, which favor either the total or fractional activity, depending on the concentrations of pyruvate and the percentage of heart-type subunits. The method has been adapted to a centrifugal analyzer, which has speeded automated isoenzyme determinations, with an accuracy comparable to that for electrophoretic methods."}
{"id": "PMID:20250", "title": "Determination of free and esterified cholesterol by a kinetic method. I. The introduction of the enzymatic method with 2,2'-azino-di-3[ethyl-benzthiazolin sulfonic acid (6)] (ABTS).", "content": "A new, simple kinetic method is described for the determination of serum cholesterol based on the oxidation of 2,2'-azino-di-3[ethyl-benzthiazolin sulfonic acid (6)] (ABTS) by use of a single aqueous reagent. This assay procedure is rapid, specific, reproducible and applicable to the measurement of free and esterified cholesterol in a continuous procedure. The method requires no prior treatment of sample and linear kinetics are obtained up to 13 mmol/l cholesterol. The use of ABTS permits the direct calculation of cholesterol concentrations from absorbance changes at 410 nm (A = epsilon - c - d).", "contents": "Determination of free and esterified cholesterol by a kinetic method. I. The introduction of the enzymatic method with 2,2'-azino-di-3[ethyl-benzthiazolin sulfonic acid (6)] (ABTS). A new, simple kinetic method is described for the determination of serum cholesterol based on the oxidation of 2,2'-azino-di-3[ethyl-benzthiazolin sulfonic acid (6)] (ABTS) by use of a single aqueous reagent. This assay procedure is rapid, specific, reproducible and applicable to the measurement of free and esterified cholesterol in a continuous procedure. The method requires no prior treatment of sample and linear kinetics are obtained up to 13 mmol/l cholesterol. The use of ABTS permits the direct calculation of cholesterol concentrations from absorbance changes at 410 nm (A = epsilon - c - d)."}
{"id": "PMID:20251", "title": "[Concanavalin A- Sepharose affinity chromatography for routine microanalysis of gamma-glutamyltransferase (author's transl)].", "content": "The separation of two molecular forms of liver gamma-glutamyltransferase is achieved by Con A-Sepharose chromatography, an adult type with high affinity to Con A and a fetal type without binding capacity to this lectin. Now we present a new method using micro-columns for affinity chromatography (gel volume 2 ml). By this rapid and inexpensive procedure it is possible to study this enzyme separation for its use in the diagnosis of liver diseases.", "contents": "[Concanavalin A- Sepharose affinity chromatography for routine microanalysis of gamma-glutamyltransferase (author's transl)]. The separation of two molecular forms of liver gamma-glutamyltransferase is achieved by Con A-Sepharose chromatography, an adult type with high affinity to Con A and a fetal type without binding capacity to this lectin. Now we present a new method using micro-columns for affinity chromatography (gel volume 2 ml). By this rapid and inexpensive procedure it is possible to study this enzyme separation for its use in the diagnosis of liver diseases."}
{"id": "PMID:20252", "title": "Determination of serum acid phosphatase in Gaucher's disease using 4-methylumbelliferyl phosphate.", "content": "We describe a new assay that is useful for identifying individuals who may be affected with Gaucher's disease. The assay involves the determination of serum acid phosphatase activity using the fluorogenic substrate 4-methylumbelliferyl phosphate. The assay measures acid phosphatase activity at pH 6.0 in the presence of 3.0 M 2-mercaptoethanol and requires a 5 microliter serum sample and a 15-min incubation period. Under these conditions, 2-mercaptoethanol preferentially inhibited the acid phosphatase activity in control serum but did not inhibit the elevated acid phosphatase present in the serum of patients with Gaucher's disease. Using this assay, we observed a 5-50-fold elevation in serum acid phosphatase activity in 8 patients with the adult, non-neuropathic form of Gaucher's disease when compared to control serum assayed under the same conditions. Serum from several heterozygotes free from pathology exhibited normal acid phosphatase activity when assayed at pH 6.0 in the presence of 2-mercaptoethanol. Acid phosphatase activity in serum from patients with prostatic cancer can be distinguished from that in Gaucher serum on the basis of the well-documented sensitivity of the former to inhibition by sodium tartrate. A serum sample from a patient with Niemann-Pick disease exhibited a mild elevation in tartrate-resistant acid phosphatase activity so that conclusive diagnosis of Gaucher's disease requires assaying leukocytes or fibroblasts from suspected patients for glucocerebroside:beta-glucosidase activity.", "contents": "Determination of serum acid phosphatase in Gaucher's disease using 4-methylumbelliferyl phosphate. We describe a new assay that is useful for identifying individuals who may be affected with Gaucher's disease. The assay involves the determination of serum acid phosphatase activity using the fluorogenic substrate 4-methylumbelliferyl phosphate. The assay measures acid phosphatase activity at pH 6.0 in the presence of 3.0 M 2-mercaptoethanol and requires a 5 microliter serum sample and a 15-min incubation period. Under these conditions, 2-mercaptoethanol preferentially inhibited the acid phosphatase activity in control serum but did not inhibit the elevated acid phosphatase present in the serum of patients with Gaucher's disease. Using this assay, we observed a 5-50-fold elevation in serum acid phosphatase activity in 8 patients with the adult, non-neuropathic form of Gaucher's disease when compared to control serum assayed under the same conditions. Serum from several heterozygotes free from pathology exhibited normal acid phosphatase activity when assayed at pH 6.0 in the presence of 2-mercaptoethanol. Acid phosphatase activity in serum from patients with prostatic cancer can be distinguished from that in Gaucher serum on the basis of the well-documented sensitivity of the former to inhibition by sodium tartrate. A serum sample from a patient with Niemann-Pick disease exhibited a mild elevation in tartrate-resistant acid phosphatase activity so that conclusive diagnosis of Gaucher's disease requires assaying leukocytes or fibroblasts from suspected patients for glucocerebroside:beta-glucosidase activity."}
{"id": "PMID:20253", "title": "New enzymatic assay of cholinesterase activity.", "content": "A new enzymatic method for the determination of serum pseudo-cholinesterase activity is described. Choline, which is liberated from benzoylcholine as substrate by cholinesterase, is oxidized by choline oxidase to betaine with the simultaneous production of hydrogen peroxide, which oxidatively couples with 4-aminoantipyrine and phenol in the presence of peroxidase to yield a chromogen with maximal absorbance at 500 nm. The calibration curve is linear up to 1500 units per liter of serum. The method is reproducible, and the results correlate well with those obtained by the method using butyrylthiocholine as substrate and 5,5'-dithiobis-(2-nitrobenzoic acid) as color reagent.", "contents": "New enzymatic assay of cholinesterase activity. A new enzymatic method for the determination of serum pseudo-cholinesterase activity is described. Choline, which is liberated from benzoylcholine as substrate by cholinesterase, is oxidized by choline oxidase to betaine with the simultaneous production of hydrogen peroxide, which oxidatively couples with 4-aminoantipyrine and phenol in the presence of peroxidase to yield a chromogen with maximal absorbance at 500 nm. The calibration curve is linear up to 1500 units per liter of serum. The method is reproducible, and the results correlate well with those obtained by the method using butyrylthiocholine as substrate and 5,5'-dithiobis-(2-nitrobenzoic acid) as color reagent."}
{"id": "PMID:20255", "title": "Quantitative elution studies in experimental immune complex and nephrotoxic nephritis.", "content": "Optimal conditions have been determined for elution of antiglomerular basement-membrane antibodies and antigen-antibody complexes from nephritic kidneys, obtained from rabbits with nephrotoxic nephritis and various forms of BSA-induced immune complex disease. Elution from kidney homogenates was performed with acid and alkaline buffers, solutions of chaotropes, urea, sodium and magnesium chloride and other agents. Functional activity of antibodies exposed to elution procedures was tested by immunofluorescence, or by a modified Farr's technique. Antibodies of progressively greater binding capacity were eluted by a stepwise acid gradient (pH 3-2--2-8) using low or high ionic strength glycine--HCl buffer. Antigen-antibody complexes were best eluted using 3 M KBr (pH 9) using several extractive steps. A stepwise alkaline gradient (pH 10-5--11-1 using 0-1 M glycine-NaOH buffer) or 8 M urea were found to be satisfactory alternative methods of eluting immune complexes. Elution procedures were best carried out in the cold in all circumstances. Other eluting agents were found to be less successful or less practical.", "contents": "Quantitative elution studies in experimental immune complex and nephrotoxic nephritis. Optimal conditions have been determined for elution of antiglomerular basement-membrane antibodies and antigen-antibody complexes from nephritic kidneys, obtained from rabbits with nephrotoxic nephritis and various forms of BSA-induced immune complex disease. Elution from kidney homogenates was performed with acid and alkaline buffers, solutions of chaotropes, urea, sodium and magnesium chloride and other agents. Functional activity of antibodies exposed to elution procedures was tested by immunofluorescence, or by a modified Farr's technique. Antibodies of progressively greater binding capacity were eluted by a stepwise acid gradient (pH 3-2--2-8) using low or high ionic strength glycine--HCl buffer. Antigen-antibody complexes were best eluted using 3 M KBr (pH 9) using several extractive steps. A stepwise alkaline gradient (pH 10-5--11-1 using 0-1 M glycine-NaOH buffer) or 8 M urea were found to be satisfactory alternative methods of eluting immune complexes. Elution procedures were best carried out in the cold in all circumstances. Other eluting agents were found to be less successful or less practical."}
{"id": "PMID:20256", "title": "Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs.", "content": "1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.", "contents": "Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels."}
{"id": "PMID:20261", "title": "Effects of urine acidification on plasma and urine phencyclidine levels in overdosage.", "content": "A gas chromatography--mass fragmentography--electron impact (GC-MS-EI) assay of phencyclidine (PCP) was adapted for human plasma and urine. This assay is specific for PCP and very sensitive (approximately 1 ng/ml). Patients with the putative diagnosis of PCP overdosage were studied to correlate plasma and urinary levels with clinical state. Urinary PCP levels were enhanced in an acid urine, which suggests that acidification of the urine is an adjunct in the therapy of PCP overdosage.", "contents": "Effects of urine acidification on plasma and urine phencyclidine levels in overdosage. A gas chromatography--mass fragmentography--electron impact (GC-MS-EI) assay of phencyclidine (PCP) was adapted for human plasma and urine. This assay is specific for PCP and very sensitive (approximately 1 ng/ml). Patients with the putative diagnosis of PCP overdosage were studied to correlate plasma and urinary levels with clinical state. Urinary PCP levels were enhanced in an acid urine, which suggests that acidification of the urine is an adjunct in the therapy of PCP overdosage."}
{"id": "PMID:20283", "title": "[Modified agar diffusion test for direct testing of the effectiveness of released antibiotics from bone cements].", "content": "A modified agar-diffusion method is used to test the bactericidal efficacy of antibacterial substances (model substance: Gentamicin) that have been mixed with Palacos osseous cement. Holes of a diameter slightly larger than the diameter of the cylindric Palacos test block are cut from the agar plate. The remaining space (inner wall of the hole--edge of the test body) is filled with various eluate media. The release of active antibacterial substances from polymethylmetacrylates can thereby be determined under nearly physiologic conditions at varying pHs by direct antibacterial testing.", "contents": "[Modified agar diffusion test for direct testing of the effectiveness of released antibiotics from bone cements]. A modified agar-diffusion method is used to test the bactericidal efficacy of antibacterial substances (model substance: Gentamicin) that have been mixed with Palacos osseous cement. Holes of a diameter slightly larger than the diameter of the cylindric Palacos test block are cut from the agar plate. The remaining space (inner wall of the hole--edge of the test body) is filled with various eluate media. The release of active antibacterial substances from polymethylmetacrylates can thereby be determined under nearly physiologic conditions at varying pHs by direct antibacterial testing."}
{"id": "PMID:20284", "title": "Clorazepate: double blind crossover comparison of a single nightly dose with diazepam thrice daily in anxiety.", "content": "In a double blind cross-over study in 40 patients with mild to moderate anxiety, clorazepate 15 mg at bedtime was as effective as diazepam on global rating and slightly superior on target symptom assessment. There was a significantly higher incidence and frequency of side effects during diazepam treatment. Occurrence of side effect related to plasma diazepam, and anxiolytic effect related to plasma nordiazepam. These results are discussed in relation to convenience of the single dose regimen and psychomotor performance.", "contents": "Clorazepate: double blind crossover comparison of a single nightly dose with diazepam thrice daily in anxiety. In a double blind cross-over study in 40 patients with mild to moderate anxiety, clorazepate 15 mg at bedtime was as effective as diazepam on global rating and slightly superior on target symptom assessment. There was a significantly higher incidence and frequency of side effects during diazepam treatment. Occurrence of side effect related to plasma diazepam, and anxiolytic effect related to plasma nordiazepam. These results are discussed in relation to convenience of the single dose regimen and psychomotor performance."}
{"id": "PMID:20291", "title": "Effect of dose on the pharmacokinetics of intravenous nicotine in the rat.", "content": "The pharmacokinetics of [methyl-14C]nicotine were evaluated in male Fischer-344 rats following the iv injection of 0.08-, 0.4-, or 0.8-mg/kg doses. Independent of dose, the concentration of nicotine declined biexponentially with a mean half-life ranging from 0.92 to 1.10 hr. However, the total plasma clearance of nicotine increased (p less than 0.05) from a mean value of 2.53 liter/hr-kg at the 0.08 mg/kg dose to mean values of 3.88 and 4.04 at the 0.4- and 0.8-mg/kg doses, respectively. There were no dose-related differences in the half-life of formation of the major metabolite, cotinine (range 0.33-0.46 hr) or the half-life of its elimination (range 5.39-6.63 hr). However, the areas under the cotinine plasma concentration-time curves did not increase proportionately with the dose of nicotine, indicating that the dose-related increase in the total plasma clearance of nicotine is not due to an increase in its biotransformation to cotinine. Similar conclusions were obtained with regard to the disposition kinetics of other polar metabolites of nicotine. The urinary excretions of nicotine and its metabolites were dose-independent.", "contents": "Effect of dose on the pharmacokinetics of intravenous nicotine in the rat. The pharmacokinetics of [methyl-14C]nicotine were evaluated in male Fischer-344 rats following the iv injection of 0.08-, 0.4-, or 0.8-mg/kg doses. Independent of dose, the concentration of nicotine declined biexponentially with a mean half-life ranging from 0.92 to 1.10 hr. However, the total plasma clearance of nicotine increased (p less than 0.05) from a mean value of 2.53 liter/hr-kg at the 0.08 mg/kg dose to mean values of 3.88 and 4.04 at the 0.4- and 0.8-mg/kg doses, respectively. There were no dose-related differences in the half-life of formation of the major metabolite, cotinine (range 0.33-0.46 hr) or the half-life of its elimination (range 5.39-6.63 hr). However, the areas under the cotinine plasma concentration-time curves did not increase proportionately with the dose of nicotine, indicating that the dose-related increase in the total plasma clearance of nicotine is not due to an increase in its biotransformation to cotinine. Similar conclusions were obtained with regard to the disposition kinetics of other polar metabolites of nicotine. The urinary excretions of nicotine and its metabolites were dose-independent."}
{"id": "PMID:20292", "title": "Pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl in the male rat.", "content": "The pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl (4-CB) was studied to determine the importance of chlorine position to the kinetics of polychlorinated biphenyl (PCB) distribution, metabolism, and excretion by the rat. Tissue samples and excreta were collected at times ranging from 2 hr to 42 days after intravenous injection of a single 0.6-mg/kg dose of 14C-labeled 4-CB. The relative fractions of 4-CB and its metabolites were determined in selected samples, and 4-hr bile cannulations were performed to establish the rate of biliary excretion. A mathematical model description of PCB kinetics in the rat was defined here for 4-CB and used to generate tissue and excretion concentration-time profiles for both the parent compound and its metabolites. Model predictions were in good agreement with the experimental data, and showed how the individual pharmacokinetics of 4-CB compared to several other PBC's. The rate of 4-CB metabolism and excretion was slower than would be predicted according to its degree of chlorination. The relative rates of metabolism for 4-CB and five other differently chlorinated biphenyls could be ordered according to the number of adjacent unsubstituted carbon-atom pairs they contained. It appears that chlorine position is more important than degree of chlorination because the former can alter the availability of vicinal hydrogens thought to facilitate rapid PCB metabolism by mammals.", "contents": "Pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl in the male rat. The pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl (4-CB) was studied to determine the importance of chlorine position to the kinetics of polychlorinated biphenyl (PCB) distribution, metabolism, and excretion by the rat. Tissue samples and excreta were collected at times ranging from 2 hr to 42 days after intravenous injection of a single 0.6-mg/kg dose of 14C-labeled 4-CB. The relative fractions of 4-CB and its metabolites were determined in selected samples, and 4-hr bile cannulations were performed to establish the rate of biliary excretion. A mathematical model description of PCB kinetics in the rat was defined here for 4-CB and used to generate tissue and excretion concentration-time profiles for both the parent compound and its metabolites. Model predictions were in good agreement with the experimental data, and showed how the individual pharmacokinetics of 4-CB compared to several other PBC's. The rate of 4-CB metabolism and excretion was slower than would be predicted according to its degree of chlorination. The relative rates of metabolism for 4-CB and five other differently chlorinated biphenyls could be ordered according to the number of adjacent unsubstituted carbon-atom pairs they contained. It appears that chlorine position is more important than degree of chlorination because the former can alter the availability of vicinal hydrogens thought to facilitate rapid PCB metabolism by mammals."}
{"id": "PMID:20293", "title": "Alteration of in vivo zoxazolamine metabolism by carbon monoxide in normal and polycyclic hydrocarbon-treated immature male rats.", "content": "The effect of carbon monoxide exposure on the in vivo metabolism  of zoxazolamine in normal (corn oil-treated) and 3,4-benzpyrene- and 3-methylcholanthrene-treated, immature, male rats was examined. Pre-exposure of the animals for 90 min followed by determination of the duration of drug action while the animals were maintained in the experimental atmosphere resulted in a qualitative difference in response between normal and polycyclic hydrocarbon-treated animals over the concentration range of 150-450 ppm CO. Corn oil-treated animals demonstrated a decreased duration of drug action when exposed to CO, indicating an increase in the bioavailability of drug for metabolism which may be a result of an increase in liver perfusion rates. In contrast, polycyclic hydrocarbon-treated animals demonstrated an increased duration of drug action on exposure to CO. The qualitative difference in response to CO exposure in the two groups of animals may be due to differences in the sensitivity of cytochrome P-450 and cytochrome P-448 with respect to complexing with CO or to lowered intracellular PO2; or to differences in the dependency on blood flow of the rate of in vivo metabolism of zoxazolamine.", "contents": "Alteration of in vivo zoxazolamine metabolism by carbon monoxide in normal and polycyclic hydrocarbon-treated immature male rats. The effect of carbon monoxide exposure on the in vivo metabolism  of zoxazolamine in normal (corn oil-treated) and 3,4-benzpyrene- and 3-methylcholanthrene-treated, immature, male rats was examined. Pre-exposure of the animals for 90 min followed by determination of the duration of drug action while the animals were maintained in the experimental atmosphere resulted in a qualitative difference in response between normal and polycyclic hydrocarbon-treated animals over the concentration range of 150-450 ppm CO. Corn oil-treated animals demonstrated a decreased duration of drug action when exposed to CO, indicating an increase in the bioavailability of drug for metabolism which may be a result of an increase in liver perfusion rates. In contrast, polycyclic hydrocarbon-treated animals demonstrated an increased duration of drug action on exposure to CO. The qualitative difference in response to CO exposure in the two groups of animals may be due to differences in the sensitivity of cytochrome P-450 and cytochrome P-448 with respect to complexing with CO or to lowered intracellular PO2; or to differences in the dependency on blood flow of the rate of in vivo metabolism of zoxazolamine."}
{"id": "PMID:20303", "title": "Developmental aspects of xenobiotic transformation.", "content": "In most laboratory animals monooxygenases are apparently absent or barely detectable in fetal organs until just before birth. In this contribution hepatic cytochrome P-450-dependent reactions in the rat are considered only. The results are interpreted on basis of the reaction scheme of Estabrook. To avoid methodological pitfalls the basic kinetics for all reactions investigated have been investigated with liver preparations from newborn and adult rats. The low monooxygenase activity of rat liver during the perinatal period can be observed even under optimal conditions for the in vitro enzyme assay. There are different developmental patterns for various reactions O-demethylation of codeine, phenazone-hydroxylation, first and second steps on N-demethylation of amidopyrine, N-demethylation of ethylmorphine. There are marked differences not only in Vmax but also in the postnatal development of Km and the inductibility by phenobarbital. Thus the existence of a different cytochrome P-450 is evident also by this approach. The low monooxygenase activity of rat liver during the perinatal period is not due to a lack of NADPH or NADH, to an age-dependent NADPH cytochrome P-450 reductase activity or to an age-dependent NADH-cytochrome P-450 reduction. Moreover this low activity is not due to an insufficient mitochondria-endoplasmic reticulum interaction. It is accompanied by low delta Amax after addition of a typical type I substrate (hexobarbital) and by a small amount of metyrapone-binding centers: it can be explained by a smaller percentage of active cytochrome P-450 in comparison to adult rat liver.", "contents": "Developmental aspects of xenobiotic transformation. In most laboratory animals monooxygenases are apparently absent or barely detectable in fetal organs until just before birth. In this contribution hepatic cytochrome P-450-dependent reactions in the rat are considered only. The results are interpreted on basis of the reaction scheme of Estabrook. To avoid methodological pitfalls the basic kinetics for all reactions investigated have been investigated with liver preparations from newborn and adult rats. The low monooxygenase activity of rat liver during the perinatal period can be observed even under optimal conditions for the in vitro enzyme assay. There are different developmental patterns for various reactions O-demethylation of codeine, phenazone-hydroxylation, first and second steps on N-demethylation of amidopyrine, N-demethylation of ethylmorphine. There are marked differences not only in Vmax but also in the postnatal development of Km and the inductibility by phenobarbital. Thus the existence of a different cytochrome P-450 is evident also by this approach. The low monooxygenase activity of rat liver during the perinatal period is not due to a lack of NADPH or NADH, to an age-dependent NADPH cytochrome P-450 reductase activity or to an age-dependent NADH-cytochrome P-450 reduction. Moreover this low activity is not due to an insufficient mitochondria-endoplasmic reticulum interaction. It is accompanied by low delta Amax after addition of a typical type I substrate (hexobarbital) and by a small amount of metyrapone-binding centers: it can be explained by a smaller percentage of active cytochrome P-450 in comparison to adult rat liver."}
{"id": "PMID:20304", "title": "A kinetic study of the pH-dependent properties of the ferric undecapeptide of cytochrome c (microperoxidase).", "content": "The ferric form of the haem undecapeptide, derived from horse cytochrome c by peptic digestion, undergoes at least three pH-induced transitions with pK values of 3.4, 5.8 and 7.6. Temperature-jump experiments suggest that the first of these is due to the binding of a deprotonated imidazole group to the feric iron while the second and third arise from the binding of the two available amino groups present (the alpha-NH2 of valine and the epsilon-NH2 of lysine). Molecular models indicate that steric retraints on the peptide dictate that these amino groups may only coordinate to iron atoms via intermolecular bonds, thus leading to the polymerization of the peptide. Cyanide binding studies are in agreement with these conclusions and also yield a value of 3.6 X 10(6) M-1 s-1 for the intrinsic combination constant of CN- anion with the haem. A model is proposed which describes the pH-dependent properties of the ferric undecapeptide.", "contents": "A kinetic study of the pH-dependent properties of the ferric undecapeptide of cytochrome c (microperoxidase). The ferric form of the haem undecapeptide, derived from horse cytochrome c by peptic digestion, undergoes at least three pH-induced transitions with pK values of 3.4, 5.8 and 7.6. Temperature-jump experiments suggest that the first of these is due to the binding of a deprotonated imidazole group to the feric iron while the second and third arise from the binding of the two available amino groups present (the alpha-NH2 of valine and the epsilon-NH2 of lysine). Molecular models indicate that steric retraints on the peptide dictate that these amino groups may only coordinate to iron atoms via intermolecular bonds, thus leading to the polymerization of the peptide. Cyanide binding studies are in agreement with these conclusions and also yield a value of 3.6 X 10(6) M-1 s-1 for the intrinsic combination constant of CN- anion with the haem. A model is proposed which describes the pH-dependent properties of the ferric undecapeptide."}
{"id": "PMID:20305", "title": "The role of cytochrome P-450 in the hydroperoxide-catalyzed oxidation of alcohols by rat-liver microsomes.", "content": "The organic hydroperoxide cumene hydroperoxide is capable of oxidizing ethanol to acetaldehyde in the presence of either catalase, purified cytochrome P-450 or rat liver microsomes. Other hemoproteins like horseradish peroxidase, cytochrome c or hemoglobin were ineffective. In addition to ethanol, higher alcohols like 1-propanol, 1-butanol and 1-pentanol are also oxidized to their corresponding aldehydes to a lesser extent. Other organic hydroxyperoxides will replace cumene hydroperoxide in oxidizing ethanol but less effectively. The cumene-hydroperoxide-dependent ethanol oxidation in microsomes was inhibited partially by cytochrome P-450 inhibitors but was unaffected by catalase inhibitors. Phenobarbital pretreatment of rats increased the specific activity of the cumene-hydroperoxide-dependent ethanol oxidation per mg of microsomes about seven-fold. The evidence suggests that cytochrome P-450 rather than catalase is the enzyme responsible for hydroperoxide-dependent ethanol oxidation. However, when H2O2 is used in place of cumene hydroperoxide, the microsomal ethanol oxidation closely resembles the catalase system.", "contents": "The role of cytochrome P-450 in the hydroperoxide-catalyzed oxidation of alcohols by rat-liver microsomes. The organic hydroperoxide cumene hydroperoxide is capable of oxidizing ethanol to acetaldehyde in the presence of either catalase, purified cytochrome P-450 or rat liver microsomes. Other hemoproteins like horseradish peroxidase, cytochrome c or hemoglobin were ineffective. In addition to ethanol, higher alcohols like 1-propanol, 1-butanol and 1-pentanol are also oxidized to their corresponding aldehydes to a lesser extent. Other organic hydroxyperoxides will replace cumene hydroperoxide in oxidizing ethanol but less effectively. The cumene-hydroperoxide-dependent ethanol oxidation in microsomes was inhibited partially by cytochrome P-450 inhibitors but was unaffected by catalase inhibitors. Phenobarbital pretreatment of rats increased the specific activity of the cumene-hydroperoxide-dependent ethanol oxidation per mg of microsomes about seven-fold. The evidence suggests that cytochrome P-450 rather than catalase is the enzyme responsible for hydroperoxide-dependent ethanol oxidation. However, when H2O2 is used in place of cumene hydroperoxide, the microsomal ethanol oxidation closely resembles the catalase system."}
{"id": "PMID:20307", "title": "Kinetics of sheep-liver cytoplasmic aldehyde dehydrogenase.", "content": "1. Sheep liver cytoplasmic aldehyde dehydrogenase showed little pH dependence of V or kcat. Some buffer anion effects were noted. 2. The oxidation of aldehydes at pH 7.6 was quantitative but irreversible. The initial velocity data indicated a sequential mechanism for the addition of substrates. Inhibition by NADH and the product analogue 2-bromo-2-phenylacetic acid, together with the known tight binding of NADH to the free enzyme, indicated an ordered mechanism with NAD+ as leading substrate. 3. Values for the rate of binding and dissociation of NAD+ were obtained from the steady-state data. The values obtained were virtually identical with those which could be calculated from the data for the horse liver cytoplasmic enzyme. Close similarities are in general apparent for the horse and sheep liver cytoplasmic enzymes and with other tissue aldehyde dehydrogenases. 4. Apparent substrate activation was observed with high concentrations of both acetaldehyde and propionaldehyde, a limiting value of 0.25s-1 being obtained for kcat. No isotope effect was observed on V using [1-2H]propionaldehyde as substrate suggesting that NADH release might be rate-limiting in the steady-state. 5. The implications of the non-linear steady-state behaviour are discussed.", "contents": "Kinetics of sheep-liver cytoplasmic aldehyde dehydrogenase. 1. Sheep liver cytoplasmic aldehyde dehydrogenase showed little pH dependence of V or kcat. Some buffer anion effects were noted. 2. The oxidation of aldehydes at pH 7.6 was quantitative but irreversible. The initial velocity data indicated a sequential mechanism for the addition of substrates. Inhibition by NADH and the product analogue 2-bromo-2-phenylacetic acid, together with the known tight binding of NADH to the free enzyme, indicated an ordered mechanism with NAD+ as leading substrate. 3. Values for the rate of binding and dissociation of NAD+ were obtained from the steady-state data. The values obtained were virtually identical with those which could be calculated from the data for the horse liver cytoplasmic enzyme. Close similarities are in general apparent for the horse and sheep liver cytoplasmic enzymes and with other tissue aldehyde dehydrogenases. 4. Apparent substrate activation was observed with high concentrations of both acetaldehyde and propionaldehyde, a limiting value of 0.25s-1 being obtained for kcat. No isotope effect was observed on V using [1-2H]propionaldehyde as substrate suggesting that NADH release might be rate-limiting in the steady-state. 5. The implications of the non-linear steady-state behaviour are discussed."}
{"id": "PMID:20308", "title": "Maldescent of the testes--an epidemiological study.", "content": "The case histories of 2,362 newborn boys were evaluated for congenital testicular maldescent. These data, obtained from the prospective follow-up study \"Pregnancy and Child Development\" sponsored by the Deutsche Forschungsgemeinschaft, are discussed in the light of new findings on morphological changes in this disorder. The aetiology of maldescent of testes is considered to be heterogenous and could not be clarified by investigating 26 factors which might be regarded as possible causes of the abnormality. The difficulties in achieving a correct classification of the various forms of maldescended testes are emphasized and are demonstrated by data from this collaborative study. Considering the frequency of non-descent at the ages of 9 months (3.3%), 18 months (2.9%), and 36 months (2.5%), we believe we have found some evidence for spontaneous descent in a proportion of cases during the first 3 years of life. If this is confirmed by proposed new studies, the findings will have to be weighed against the recommendations of the 1974 International Health Foundation that therapy should be performed during the 2nd year of life or earlier.", "contents": "Maldescent of the testes--an epidemiological study. The case histories of 2,362 newborn boys were evaluated for congenital testicular maldescent. These data, obtained from the prospective follow-up study \"Pregnancy and Child Development\" sponsored by the Deutsche Forschungsgemeinschaft, are discussed in the light of new findings on morphological changes in this disorder. The aetiology of maldescent of testes is considered to be heterogenous and could not be clarified by investigating 26 factors which might be regarded as possible causes of the abnormality. The difficulties in achieving a correct classification of the various forms of maldescended testes are emphasized and are demonstrated by data from this collaborative study. Considering the frequency of non-descent at the ages of 9 months (3.3%), 18 months (2.9%), and 36 months (2.5%), we believe we have found some evidence for spontaneous descent in a proportion of cases during the first 3 years of life. If this is confirmed by proposed new studies, the findings will have to be weighed against the recommendations of the 1974 International Health Foundation that therapy should be performed during the 2nd year of life or earlier."}
{"id": "PMID:20309", "title": "Adult height of patients treated in childhood for undescended testes.", "content": "101 patients successfully treated for undescended testes with human chorionic gonadotrophin (HCG) or with HCG followed by surgery reached normal adult heights. Deviations from normal growth in individual patients did not appear to be related either to their earlier undescended testes or to the successful therapy, but rather to their genetic background. Therefore, apart from patients with chromosomal abnormalities and other primary causes for maldescent of the testes, boys with undescended testes show a normal distribution for height and do not represent a different population with regard to growth.", "contents": "Adult height of patients treated in childhood for undescended testes. 101 patients successfully treated for undescended testes with human chorionic gonadotrophin (HCG) or with HCG followed by surgery reached normal adult heights. Deviations from normal growth in individual patients did not appear to be related either to their earlier undescended testes or to the successful therapy, but rather to their genetic background. Therefore, apart from patients with chromosomal abnormalities and other primary causes for maldescent of the testes, boys with undescended testes show a normal distribution for height and do not represent a different population with regard to growth."}
{"id": "PMID:20310", "title": "Adult metachromatic leukodystrophy. I. Clinical manifestation in a female aged 44 years, previously diagnosed in the preclinical state.", "content": "In a 5-year follow-up of a case of adult metachromatic leukodystrophy, already diagnosed in the preclinical stage, the development of the symptoms of this disease could be studied in detail: initially, lack of drive, emotional lability and depressive mood. At the same time, pain in the arms and beginning gait disturbance. Later, impairment of memory and concentration, disorientation, inadequate behavior and progression of gait disturbance. Finally spastic atactic gait with small steps and dyspractic components, coordination disturbances with writing dysfunction, fast dysarthric speech, hyperkinetic activity, compulsory emotional outbursts and progressive dementia. Only minor neurological signs such as reflex abnormalities. In the EEG, slight slowing of frequencies compared to earlier tracings. Increasing diminution of nerve conduction velocity in the lower limbs. Only minor increase of CSF protein (51 mg%). In spite of normal vision, evoked visual potentials abnormal, response of optical and electrical blink reflexes delayed. Imperfect filling of gallbladder. No significant quantitative changes of the biochemical parameters compared with the findings made 5 years earlier (excretion of urinary sulfatides, diminished activity of arylfulfatase A in urine and leukocytes).", "contents": "Adult metachromatic leukodystrophy. I. Clinical manifestation in a female aged 44 years, previously diagnosed in the preclinical state. In a 5-year follow-up of a case of adult metachromatic leukodystrophy, already diagnosed in the preclinical stage, the development of the symptoms of this disease could be studied in detail: initially, lack of drive, emotional lability and depressive mood. At the same time, pain in the arms and beginning gait disturbance. Later, impairment of memory and concentration, disorientation, inadequate behavior and progression of gait disturbance. Finally spastic atactic gait with small steps and dyspractic components, coordination disturbances with writing dysfunction, fast dysarthric speech, hyperkinetic activity, compulsory emotional outbursts and progressive dementia. Only minor neurological signs such as reflex abnormalities. In the EEG, slight slowing of frequencies compared to earlier tracings. Increasing diminution of nerve conduction velocity in the lower limbs. Only minor increase of CSF protein (51 mg%). In spite of normal vision, evoked visual potentials abnormal, response of optical and electrical blink reflexes delayed. Imperfect filling of gallbladder. No significant quantitative changes of the biochemical parameters compared with the findings made 5 years earlier (excretion of urinary sulfatides, diminished activity of arylfulfatase A in urine and leukocytes)."}
{"id": "PMID:20311", "title": "Adult metachromatic leukodystrophy. II. Ultrastructural findings in peripheral nerve and skeletal muscle.", "content": "Sural nerve biopsy in a 44-year-old woman with adult metachromatic leukodystrophy (MLD) confirmed by deficient arylsulfatase-A activity, showed a reduction in the number of large and small myelinated axons, and sparse metachromatic material. Ultrastructurally, the latter consisted of various types of residual bodies including the tufaceous and prismatic forms typical of MLD. In the striated muscle, large amounts of regular lipofuscin but no MLD-characteristic inclusions were encountered. Inclusion-bearing mitochondria in the muscle appeared to be an incidental finding.", "contents": "Adult metachromatic leukodystrophy. II. Ultrastructural findings in peripheral nerve and skeletal muscle. Sural nerve biopsy in a 44-year-old woman with adult metachromatic leukodystrophy (MLD) confirmed by deficient arylsulfatase-A activity, showed a reduction in the number of large and small myelinated axons, and sparse metachromatic material. Ultrastructurally, the latter consisted of various types of residual bodies including the tufaceous and prismatic forms typical of MLD. In the striated muscle, large amounts of regular lipofuscin but no MLD-characteristic inclusions were encountered. Inclusion-bearing mitochondria in the muscle appeared to be an incidental finding."}
{"id": "PMID:20312", "title": "Carbohydrase activity in the digestive system of some teleost fishes.", "content": "The activity of carbohydrases in Puntius sophore (Ham.), Channa gachua (Ham.) and Cirrhinus mrigala (Ham.) has been studied. The carbohydrases have been found in the stomach, intestinal bulb, intestine, pyloric caeca and the hepato-pancreas. The hepatopancreas is the main site of production of these enzymes and it is in this organ and the intestine that their activity is highest. Their pH optimum lies between 5.4 and 6.4. The enzyme equipment in the teleost is adapted to their respective food and feeding habits both qualitatively and quantitatively. In Puntius (omnivorous) and Cirrhinus (herbivorous) all three carbohydrases, namely amylase (EC 3.2.1.1.), sucrase (EC 3.2.1.26.) and raffinase, while in Channa (carnivorous) only amylase and sucrase have been found to be active. In Cirrhinus mrigala, which is predominantly a herbivorous species, the concentration of carbohydrases is higher than those in the other two fishes.", "contents": "Carbohydrase activity in the digestive system of some teleost fishes. The activity of carbohydrases in Puntius sophore (Ham.), Channa gachua (Ham.) and Cirrhinus mrigala (Ham.) has been studied. The carbohydrases have been found in the stomach, intestinal bulb, intestine, pyloric caeca and the hepato-pancreas. The hepatopancreas is the main site of production of these enzymes and it is in this organ and the intestine that their activity is highest. Their pH optimum lies between 5.4 and 6.4. The enzyme equipment in the teleost is adapted to their respective food and feeding habits both qualitatively and quantitatively. In Puntius (omnivorous) and Cirrhinus (herbivorous) all three carbohydrases, namely amylase (EC 3.2.1.1.), sucrase (EC 3.2.1.26.) and raffinase, while in Channa (carnivorous) only amylase and sucrase have been found to be active. In Cirrhinus mrigala, which is predominantly a herbivorous species, the concentration of carbohydrases is higher than those in the other two fishes."}
{"id": "PMID:20313", "title": "Aminotripeptidase (EC E.4.1.3) activity in the digestive system of some teleost fishes.", "content": "Aminotripeptidase (EC 3.4.1.3) has been found to be present in the intestinal mucosa, hepatopancreas and the pyloric caeca of the three fished examined. The pH optimum of the enzyme ranges from 6.6 to 7.6. The pH optimum varies from species to species and also from section to section of the gut in the same species. The enzyme is most active in the carnivorous Channa gachua in comparison to the other fishes studied.", "contents": "Aminotripeptidase (EC E.4.1.3) activity in the digestive system of some teleost fishes. Aminotripeptidase (EC 3.4.1.3) has been found to be present in the intestinal mucosa, hepatopancreas and the pyloric caeca of the three fished examined. The pH optimum of the enzyme ranges from 6.6 to 7.6. The pH optimum varies from species to species and also from section to section of the gut in the same species. The enzyme is most active in the carnivorous Channa gachua in comparison to the other fishes studied."}
{"id": "PMID:20314", "title": "The interaction of 1-(2(diarylmethoxy)ethyl)aziridines with histamine receptors in the longitudinal muscle strip of the guinea pig ileum.", "content": "The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum.", "contents": "The interaction of 1-(2(diarylmethoxy)ethyl)aziridines with histamine receptors in the longitudinal muscle strip of the guinea pig ileum. The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum."}
{"id": "PMID:20315", "title": "[Comparative biochemical studies of placental alkaline phosphatase in animals (author's transl)].", "content": "Biochemical properties of alkaline phosphatase (ALP) from placenta were compared between man, dog, cat, rabbit and cattle. 1) Optimum pH of the enzyme was essentially identical through the species of the animals but the inhibition of L-phenylalanine was clearly demonstrable with human ALP but little with that of other animals. 2) ALP of human placenta was not inactivated by heating at 65 degrees C for 15 min. but one of the other animals was thermolabile. Such thermostability of human placental ALP almost disappeared after treatment with EDTA, suggesting that the divalent metal ions were required for the thermostability. 3) Activities of placental ALP were inhibited by cationsurfactants in human and rat but not in the other animals, while the inhibition by DOC-Na, an anion-surfactant, was seen only in human. 4) The affinity to beta-glycerophosphae of placental ALP was seen only in human.", "contents": "[Comparative biochemical studies of placental alkaline phosphatase in animals (author's transl)]. Biochemical properties of alkaline phosphatase (ALP) from placenta were compared between man, dog, cat, rabbit and cattle. 1) Optimum pH of the enzyme was essentially identical through the species of the animals but the inhibition of L-phenylalanine was clearly demonstrable with human ALP but little with that of other animals. 2) ALP of human placenta was not inactivated by heating at 65 degrees C for 15 min. but one of the other animals was thermolabile. Such thermostability of human placental ALP almost disappeared after treatment with EDTA, suggesting that the divalent metal ions were required for the thermostability. 3) Activities of placental ALP were inhibited by cationsurfactants in human and rat but not in the other animals, while the inhibition by DOC-Na, an anion-surfactant, was seen only in human. 4) The affinity to beta-glycerophosphae of placental ALP was seen only in human."}
{"id": "PMID:20318", "title": "Experimental renal papillary necrosis. Effects of beta adrenergic receptor blockade, heparin and hydrocortisone.", "content": "Renal papillary necrosis was induced in rats by daily subcutaneous injection of 15 mg 2-bromoethylamine hydrobromide (BEA) per 100 g of body weight for 2 successive days. This dose was 50% higher than that reported previously. Beta adrenergic receptor blockade with oxyprenolol did not influence the kidney damage. The administration of heparin did not show any effect. The doses applied did not induce the incoagulability for a sufficient period of time. On the contrary, treatment with hydrocortisone decreased papillary necrosis without inducing increased diuresis.", "contents": "Experimental renal papillary necrosis. Effects of beta adrenergic receptor blockade, heparin and hydrocortisone. Renal papillary necrosis was induced in rats by daily subcutaneous injection of 15 mg 2-bromoethylamine hydrobromide (BEA) per 100 g of body weight for 2 successive days. This dose was 50% higher than that reported previously. Beta adrenergic receptor blockade with oxyprenolol did not influence the kidney damage. The administration of heparin did not show any effect. The doses applied did not induce the incoagulability for a sufficient period of time. On the contrary, treatment with hydrocortisone decreased papillary necrosis without inducing increased diuresis."}
{"id": "PMID:20319", "title": "Hypoxia in fibroblast cultures. 3. 35S-sulfate incorporation into acid mucopolysaccharides as influenced by 5% O2 hypoxia with simultaneous changes in the lactate-and H-ion concentrations.", "content": "The influence of 5% O2 hypoxia on the 35S-sulfate incorporation into different mucopolysaccharide fractions was studied in monolayer cultures of embryonic rat fibroblasts before reaching the stationary phase. Besides the O2 concentration also the pH value and lactate concentration were varied in the experiments. The results are valid for proliferating cell cultures.", "contents": "Hypoxia in fibroblast cultures. 3. 35S-sulfate incorporation into acid mucopolysaccharides as influenced by 5% O2 hypoxia with simultaneous changes in the lactate-and H-ion concentrations. The influence of 5% O2 hypoxia on the 35S-sulfate incorporation into different mucopolysaccharide fractions was studied in monolayer cultures of embryonic rat fibroblasts before reaching the stationary phase. Besides the O2 concentration also the pH value and lactate concentration were varied in the experiments. The results are valid for proliferating cell cultures."}
{"id": "PMID:20320", "title": "Hypoxia in fibroblast cultures. 4. Cell density, glucose utilization and acid mucopolysaccharides in 1% O2 concentration.", "content": "Secondary cultures of embryonic rat fibroblasts incubated in Eagle medium with Hepes buffer at pH 6.6 and 7.4 were maintained in hypoxia of 1% O2 for 48 hours. The acid mucopolysaccharides were isolated from medium plus cells and fractionated on cellulose microcolumns according to SVEJCAR and ROBERTSON (1967). Glucose utilization, lactate production, quantity of total MPS and changes in the MPS distribution pattern were correlated with cell density.", "contents": "Hypoxia in fibroblast cultures. 4. Cell density, glucose utilization and acid mucopolysaccharides in 1% O2 concentration. Secondary cultures of embryonic rat fibroblasts incubated in Eagle medium with Hepes buffer at pH 6.6 and 7.4 were maintained in hypoxia of 1% O2 for 48 hours. The acid mucopolysaccharides were isolated from medium plus cells and fractionated on cellulose microcolumns according to SVEJCAR and ROBERTSON (1967). Glucose utilization, lactate production, quantity of total MPS and changes in the MPS distribution pattern were correlated with cell density."}
{"id": "PMID:20321", "title": "The problem of sea urchin egg fertilization and its implications for biological studies.", "content": "The analysis of sea urchin egg fertilization shows that several phenomena common to other biological systems are involved: cell recognition, cell fusion, exocytosis and initiation of mitotic activity. Both the role of calcium ions in cell fusion and exocytosis and the function of the cell surface in the initiation of mitotic activity appear to have general applicability. The study of fertilization can contribute to the elucidation of these processes and, reciprocally, progress in this field can help to advance our understanding of the mechanisms of fertilization in sea urchins and other organisms.", "contents": "The problem of sea urchin egg fertilization and its implications for biological studies. The analysis of sea urchin egg fertilization shows that several phenomena common to other biological systems are involved: cell recognition, cell fusion, exocytosis and initiation of mitotic activity. Both the role of calcium ions in cell fusion and exocytosis and the function of the cell surface in the initiation of mitotic activity appear to have general applicability. The study of fertilization can contribute to the elucidation of these processes and, reciprocally, progress in this field can help to advance our understanding of the mechanisms of fertilization in sea urchins and other organisms."}
{"id": "PMID:20323", "title": "Hydrogen peroxide generation in Trypanosoma cruzi.", "content": "Homogenates from T. cruzi epimastigotes produced 3.4 pmoles H2O2/min 10(6) cells, as detected by the cytochrome c peroxidase assay. Addition of NADH or NADPH increased H2O2 production by a factor of 3 and 5, respectively. When supplemented with NADH and NADPH, the mitochondrial, microsomal and supernatant fractions produced H2O2, the soluble fraction and the mitochondrial membranes being apparently the main generators of H2O2. The epimastigote homogenates showed cyanide-sensitive superoxide dismutase activity, equivalent to 0.28 microgram bovine superoxide dismutase per mg homogenate protein.", "contents": "Hydrogen peroxide generation in Trypanosoma cruzi. Homogenates from T. cruzi epimastigotes produced 3.4 pmoles H2O2/min 10(6) cells, as detected by the cytochrome c peroxidase assay. Addition of NADH or NADPH increased H2O2 production by a factor of 3 and 5, respectively. When supplemented with NADH and NADPH, the mitochondrial, microsomal and supernatant fractions produced H2O2, the soluble fraction and the mitochondrial membranes being apparently the main generators of H2O2. The epimastigote homogenates showed cyanide-sensitive superoxide dismutase activity, equivalent to 0.28 microgram bovine superoxide dismutase per mg homogenate protein."}
{"id": "PMID:20324", "title": "[Effect of several neuroleptic, adreno-, sympatho- and cholinolytic substances on the development of experimental cerebral edema induced by nicotine].", "content": "The influence of some neuroleptic, adreno, sympatho- and cholinolytic substances on the development of experimental brain edema induced with nicotine was studied in tests conducted on rats. It was ascertained that marked antiedemic properties display drugs blocking the alpha-adrenoreceptors (phentolamine, dopegit), the neuroleptic chlorpromazine and central M-cholinolytics (benactizine). Weak action exert central H-cholinolytics (difacil trasentin) and the neuroleptic galoperidol. Sympatho- and beta-adrenolytics (guanethidine, alpha-methyltyrosine, obsidan), and also the neuroleptic triphthazine fail to prevent the development of an experimental brain edema. It is presumed that a brain edema induced with nicotine comes as a result of the catecholamines liberation and is also due to stimulation of alpha-adrenoreactive systems.", "contents": "[Effect of several neuroleptic, adreno-, sympatho- and cholinolytic substances on the development of experimental cerebral edema induced by nicotine]. The influence of some neuroleptic, adreno, sympatho- and cholinolytic substances on the development of experimental brain edema induced with nicotine was studied in tests conducted on rats. It was ascertained that marked antiedemic properties display drugs blocking the alpha-adrenoreceptors (phentolamine, dopegit), the neuroleptic chlorpromazine and central M-cholinolytics (benactizine). Weak action exert central H-cholinolytics (difacil trasentin) and the neuroleptic galoperidol. Sympatho- and beta-adrenolytics (guanethidine, alpha-methyltyrosine, obsidan), and also the neuroleptic triphthazine fail to prevent the development of an experimental brain edema. It is presumed that a brain edema induced with nicotine comes as a result of the catecholamines liberation and is also due to stimulation of alpha-adrenoreactive systems."}
{"id": "PMID:20325", "title": "[Pharmacologic study of clofelin].", "content": "Clofelin--2-(2,6-dichlorphenylamino)-2-imidasoline, an analoque of foreign-made clonidine (St155, catapresan, hemiton, etc) was subjected to a pharmacological study. In animals the drug produces first a rise and then protracted fall of the arterial pressure, reduces the frequency of cardiac contractions, lessens reflex hypertension that develops on compression of carotid arteries. When used in low doses it depresses the motor activity in unanesthetized animals and produces symptoms that bear evidence to its adrenomimetic action, e.g. exophthalmos, piloerection. Hypertension provoked by clofelin is caused by its peripheral and hypotension--by the central alpha-adrenomimetic action. The results of the present investigation prove clofelin to be identical with corresponding foreign drugs.", "contents": "[Pharmacologic study of clofelin]. Clofelin--2-(2,6-dichlorphenylamino)-2-imidasoline, an analoque of foreign-made clonidine (St155, catapresan, hemiton, etc) was subjected to a pharmacological study. In animals the drug produces first a rise and then protracted fall of the arterial pressure, reduces the frequency of cardiac contractions, lessens reflex hypertension that develops on compression of carotid arteries. When used in low doses it depresses the motor activity in unanesthetized animals and produces symptoms that bear evidence to its adrenomimetic action, e.g. exophthalmos, piloerection. Hypertension provoked by clofelin is caused by its peripheral and hypotension--by the central alpha-adrenomimetic action. The results of the present investigation prove clofelin to be identical with corresponding foreign drugs."}
{"id": "PMID:20326", "title": "[Mechanism of the antianginal action of oxyfedrine].", "content": "Oxyphedrine was found to depress the tonicity of coronary vessels, increase the coronary circulation volume, the oxygen uptake by the heart and also to exert a positive inoand chronotropic action in test with urethan and cloralose anesthetized cats. These effects were caused by stimulation of the beta-adrenoreceptors of the heart and vessels. In non-anesthetized cats oxyphedrine did not produce tachycardia. Furthermore, under certain conditions (when superimposed on a preliminary administration of practolol- a beta-blocking agent) oxyphedrine can exert a direct inhibitory action on the myocardium.", "contents": "[Mechanism of the antianginal action of oxyfedrine]. Oxyphedrine was found to depress the tonicity of coronary vessels, increase the coronary circulation volume, the oxygen uptake by the heart and also to exert a positive inoand chronotropic action in test with urethan and cloralose anesthetized cats. These effects were caused by stimulation of the beta-adrenoreceptors of the heart and vessels. In non-anesthetized cats oxyphedrine did not produce tachycardia. Furthermore, under certain conditions (when superimposed on a preliminary administration of practolol- a beta-blocking agent) oxyphedrine can exert a direct inhibitory action on the myocardium."}
{"id": "PMID:20330", "title": "Peinamine, a new bisbenzylisoquinoline alkaloid from arrow tips (pei-nam\u00f4) of the Upper Orinoco.", "content": "A new bisbenzylisoquinoline alkaloid has been isolated from a curare of the Upper Orinoco region. The curare is made by Indians from an unknown plant (probably Menispermacea) and is kept on arrow tips. The structure of the alkaloid, named peinamine, has been elucidated on the basis of its chemical reactions and spectroscopic data (N.M.R., M.S. and O.R.D.).", "contents": "Peinamine, a new bisbenzylisoquinoline alkaloid from arrow tips (pei-nam\u00f4) of the Upper Orinoco. A new bisbenzylisoquinoline alkaloid has been isolated from a curare of the Upper Orinoco region. The curare is made by Indians from an unknown plant (probably Menispermacea) and is kept on arrow tips. The structure of the alkaloid, named peinamine, has been elucidated on the basis of its chemical reactions and spectroscopic data (N.M.R., M.S. and O.R.D.)."}
{"id": "PMID:20327", "title": "[Study of phenothiazine binding to membranes by the fluorescent probe method].", "content": "Binding of chlorpromazine, etaperazine and triftazine with model phospholipid membranes was investigated by using a 3-methoxybenzanthrone (MBA) fluorescent probe. All these preparations interacted with the membranes, this being registered by the MBA fluorescence extinction. The phenothiazine molecules bound with the membrane are localized in its superficial layer and extinguish the MBA fluorescence in different ways. The chlorpromazine binding was heterogenous and there are, apparently, 2 different ways of its molecules combination with the membranes. The effective extinction of MBA by phenothiazine increased in the following order: chlorpromazine, etaperazine, triftazine.", "contents": "[Study of phenothiazine binding to membranes by the fluorescent probe method]. Binding of chlorpromazine, etaperazine and triftazine with model phospholipid membranes was investigated by using a 3-methoxybenzanthrone (MBA) fluorescent probe. All these preparations interacted with the membranes, this being registered by the MBA fluorescence extinction. The phenothiazine molecules bound with the membrane are localized in its superficial layer and extinguish the MBA fluorescence in different ways. The chlorpromazine binding was heterogenous and there are, apparently, 2 different ways of its molecules combination with the membranes. The effective extinction of MBA by phenothiazine increased in the following order: chlorpromazine, etaperazine, triftazine."}
{"id": "PMID:20331", "title": "Effect of dibenzepin hydrochloride on the oxygen, glucose uptake and oxidative phosphorylation of rat brain in vitro.", "content": "Dibenzepin hydrochloride (10(-3) M) decreases the oxygen uptake of whole brain homogenates and uncouples brain mitochondrial oxidative phosphorylation. At the same concentration this drug inhibits oxygen uptake of rat brain slices when calcium is absent in the incubation or then contains an excess of potassium.", "contents": "Effect of dibenzepin hydrochloride on the oxygen, glucose uptake and oxidative phosphorylation of rat brain in vitro. Dibenzepin hydrochloride (10(-3) M) decreases the oxygen uptake of whole brain homogenates and uncouples brain mitochondrial oxidative phosphorylation. At the same concentration this drug inhibits oxygen uptake of rat brain slices when calcium is absent in the incubation or then contains an excess of potassium."}
{"id": "PMID:20328", "title": "[Long-term experiments on toleration of the ganglionic blockader hygronium].", "content": "In tests set up on albino rats, guinea pigs and rabbits the chronic toxicity of hygronium--a new original ganglion blocking agent of a short-term action was studied. With its daily intraperitoneal administration for 14 days in doses of 10 and 40 mg/kg (1/10 and 1/3 DL50) the drug produces in some of the animals, chiefly in rabbits and guinea pigs receiving 40 mg/kg, readily reversible histological changes in some of their internal organs. Hygronium does not cause any local irritating effect", "contents": "[Long-term experiments on toleration of the ganglionic blockader hygronium]. In tests set up on albino rats, guinea pigs and rabbits the chronic toxicity of hygronium--a new original ganglion blocking agent of a short-term action was studied. With its daily intraperitoneal administration for 14 days in doses of 10 and 40 mg/kg (1/10 and 1/3 DL50) the drug produces in some of the animals, chiefly in rabbits and guinea pigs receiving 40 mg/kg, readily reversible histological changes in some of their internal organs. Hygronium does not cause any local irritating effect"}
{"id": "PMID:20329", "title": "[Effect of contrast media on the rate of oxidation of NADP.H and NAD.H by rat liver microsomes].", "content": "The effect of roentgen-contrast media on the activity of the NADP'N and NAD'N-dependent electron-transport chains of the rats liver microsomes was studied. Bilignost, cardiotrast, triiotrast and triombrin are shown to lower the rate of the NADP'N oxidation by the rats' liver microsomes and have no effect (except for triiotrast) upon the rate of the NAD'N oxidation. It is presumed that the relative resistance of the NAD'N-specific flavoproteid is due to the presence of a hydrophobic layer impervious to the polar molecules of the contrast media.", "contents": "[Effect of contrast media on the rate of oxidation of NADP.H and NAD.H by rat liver microsomes]. The effect of roentgen-contrast media on the activity of the NADP'N and NAD'N-dependent electron-transport chains of the rats liver microsomes was studied. Bilignost, cardiotrast, triiotrast and triombrin are shown to lower the rate of the NADP'N oxidation by the rats' liver microsomes and have no effect (except for triiotrast) upon the rate of the NAD'N oxidation. It is presumed that the relative resistance of the NAD'N-specific flavoproteid is due to the presence of a hydrophobic layer impervious to the polar molecules of the contrast media."}
{"id": "PMID:20337", "title": "Excretion in insects: function of gut and rectum in concentrating and diluting the urine.", "content": "The diverse excretory systems of insects exhibit several features that appear unusual when comparisons are made with the mammalian kidney. Secretion by the Malpighian tubules of a fluid that is unlike the blood in composition, substitutes for glomerular filtration. Various reabsorptive functions, such as volume reduction, regulation of individual electrolytes, adjustment of osmotic concentration and pH regulation, which are associated with distinct renal segments in the mammalian kidney, all occur simultaneously in the rectum of terrestrial insects. Involvement of an extracellular molecular sieve in selective reabsorption is novel. As far as water transport is concerned, the rectal pads of the cockroach and locust appear to accomplish, across a single layer of cells, the same function as the countercurrent multiplier system of the mammalian kidney with its several epithelial layers. Direct absorption of water vapor in the rectum of some insects from atmospheres of low relative humidity, clearly involves quite different and unknown mechanisms. Finally, saline-water insect larvae produce hyperosmotic excreta by direct secretion of ions into the rectal lumen. They can adjust individual transport processes to form various secretions, which are appropriate to the natural waters of diverse chemical types in which these larvae thrive.", "contents": "Excretion in insects: function of gut and rectum in concentrating and diluting the urine. The diverse excretory systems of insects exhibit several features that appear unusual when comparisons are made with the mammalian kidney. Secretion by the Malpighian tubules of a fluid that is unlike the blood in composition, substitutes for glomerular filtration. Various reabsorptive functions, such as volume reduction, regulation of individual electrolytes, adjustment of osmotic concentration and pH regulation, which are associated with distinct renal segments in the mammalian kidney, all occur simultaneously in the rectum of terrestrial insects. Involvement of an extracellular molecular sieve in selective reabsorption is novel. As far as water transport is concerned, the rectal pads of the cockroach and locust appear to accomplish, across a single layer of cells, the same function as the countercurrent multiplier system of the mammalian kidney with its several epithelial layers. Direct absorption of water vapor in the rectum of some insects from atmospheres of low relative humidity, clearly involves quite different and unknown mechanisms. Finally, saline-water insect larvae produce hyperosmotic excreta by direct secretion of ions into the rectal lumen. They can adjust individual transport processes to form various secretions, which are appropriate to the natural waters of diverse chemical types in which these larvae thrive."}
{"id": "PMID:20338", "title": "The frequency of Y chromatin-positive spermatozoa during in vitro penetration tests under various experimental conditions.", "content": "Complete analysis were carried out on the semen of 55 subjects. The semen was then investigated by using the fluorescent microscopic technique to determine the percentage proportion of Y chromatin-bearing spermatozoa. After staining with quinacrine mustard, an average Y chromatin frequency of 48.2% +/- 2.9% was recorded. With this spermatozoal material, 139 in vitro penetration tests were carried out with cervical mucus. After penetration there was a small, but statistically significant, increase in the percentage of Y spermatozoa (to 52.7% +/- 3.8%). The figures thus recorded were then correlated under variable experimental conditions in addition to variable semen parameters. The ratio of X:Y spermatozoa was related to the duration of the penetration tests, varying temperatures during the penetration, varying acid values of semen and cervical secretion, and also to the value of sperm motility in the semen analysis and to cervical factors. None of the above variables had any measurable influence on the percentage distribution of X and Y spermatozoa during in vitro penetration.", "contents": "The frequency of Y chromatin-positive spermatozoa during in vitro penetration tests under various experimental conditions. Complete analysis were carried out on the semen of 55 subjects. The semen was then investigated by using the fluorescent microscopic technique to determine the percentage proportion of Y chromatin-bearing spermatozoa. After staining with quinacrine mustard, an average Y chromatin frequency of 48.2% +/- 2.9% was recorded. With this spermatozoal material, 139 in vitro penetration tests were carried out with cervical mucus. After penetration there was a small, but statistically significant, increase in the percentage of Y spermatozoa (to 52.7% +/- 3.8%). The figures thus recorded were then correlated under variable experimental conditions in addition to variable semen parameters. The ratio of X:Y spermatozoa was related to the duration of the penetration tests, varying temperatures during the penetration, varying acid values of semen and cervical secretion, and also to the value of sperm motility in the semen analysis and to cervical factors. None of the above variables had any measurable influence on the percentage distribution of X and Y spermatozoa during in vitro penetration."}
{"id": "PMID:20339", "title": "Xenogeneic neoplastic transplants in adult rats pretreated with thymic foetal extracts.", "content": "The paper deals with the effect of thymic extracts from young foetal pigs and calves on the development of tumour xenografts, i.e. mouse ascites Ehrlich carcinoma and hamster malignant melanoma, in rats. The results of experiments showed that Ehrlich carcinoma developed in 4 out of 72 animals, i.e., in those animals which had received thymic extracts from young foetal pigs, Ehrlich carcinoma led to their death. Ehrlich carcinoma assumed a solid form and the cells changed in their shape. It developed normally, when retransplanted to mice. Hamster melanoma, when transplanted to rats given thymic extracts from young foetal calves, developed and survived for long periods of time (in one animal up to 190 days, and in the remaining animals much longer than in the controls and the animals injected with liver extracts from young foetal calves). The melanoma xenograft was not morphologically changed. A normal development of the malignant process occurred when melanoma was retransplanted to hamsters. Animals injected with thymic extracts from young foetal calves exhibited lymphopoenia and a fall in gamma globulin levels before tumour transplantation.", "contents": "Xenogeneic neoplastic transplants in adult rats pretreated with thymic foetal extracts. The paper deals with the effect of thymic extracts from young foetal pigs and calves on the development of tumour xenografts, i.e. mouse ascites Ehrlich carcinoma and hamster malignant melanoma, in rats. The results of experiments showed that Ehrlich carcinoma developed in 4 out of 72 animals, i.e., in those animals which had received thymic extracts from young foetal pigs, Ehrlich carcinoma led to their death. Ehrlich carcinoma assumed a solid form and the cells changed in their shape. It developed normally, when retransplanted to mice. Hamster melanoma, when transplanted to rats given thymic extracts from young foetal calves, developed and survived for long periods of time (in one animal up to 190 days, and in the remaining animals much longer than in the controls and the animals injected with liver extracts from young foetal calves). The melanoma xenograft was not morphologically changed. A normal development of the malignant process occurred when melanoma was retransplanted to hamsters. Animals injected with thymic extracts from young foetal calves exhibited lymphopoenia and a fall in gamma globulin levels before tumour transplantation."}
{"id": "PMID:20342", "title": "Influence of steroid structure in relation to liver metabolism during endotoxin lethality in mice.", "content": "The influence of a number of steroid molecules on hepatic metabolism was determined in relationship to their ability to alter endotoxin lethality in intact mice. Progesterone, testosterone, estradiol, pregnenolone-16-alpha-carbonitrile and spironolactone did not alter endotoxin lethality, liver glycogen or tryptophan pyrrolase (TP) levels; all these materials increased liver tyrosine transaminase (TT) levels most probably due to mediation by endogenously liberated glucocorticoid hormones. Aldosterone and deoxycorticosterone induced liver TP, TT and glycogen but did not protect against lethality. Cortisone, hydrocortisone, triamcinolone, dexamethasone and 9-alpha-fluorohydrocortisone protected against lethality, increased liver glycogen and TT, but only triamcinolone induced liver TP. Collectively, there was no clear relationship between the protective effect and the increase or decrease of a given liver process. These further emphasize the need to reconsider molecular mechanisms of endotoxic reactions.", "contents": "Influence of steroid structure in relation to liver metabolism during endotoxin lethality in mice. The influence of a number of steroid molecules on hepatic metabolism was determined in relationship to their ability to alter endotoxin lethality in intact mice. Progesterone, testosterone, estradiol, pregnenolone-16-alpha-carbonitrile and spironolactone did not alter endotoxin lethality, liver glycogen or tryptophan pyrrolase (TP) levels; all these materials increased liver tyrosine transaminase (TT) levels most probably due to mediation by endogenously liberated glucocorticoid hormones. Aldosterone and deoxycorticosterone induced liver TP, TT and glycogen but did not protect against lethality. Cortisone, hydrocortisone, triamcinolone, dexamethasone and 9-alpha-fluorohydrocortisone protected against lethality, increased liver glycogen and TT, but only triamcinolone induced liver TP. Collectively, there was no clear relationship between the protective effect and the increase or decrease of a given liver process. These further emphasize the need to reconsider molecular mechanisms of endotoxic reactions."}
{"id": "PMID:20343", "title": "A comparison of D & C and vacuum aspiration for performing first trimester abortion.", "content": "In a study of techniques for first trimester abortion conducted at Kandang Kerbau Hospital in Singapore from September 1973 to April 1975, 420 physically healthy gravidas were randomly assigned to one of two treatment groups either by D & C or vacuum aspiration. Half of the patients in each group were 6 to 10 menstrual weeks' gestation and half were 11 to 12 week's gestation. The numbers of women with one or more complications were the same for the two treatment groups, but were significantly less when termination was carried out at 11 to 12 weeks' gestation. Estimated blood loss was significantly lower for patients treated by VA (32.3 ml) than for patients treated by D & C (39.0 ml) at 6 to 10 week's gestation, but the difference in blood loss was not statistically significant at 11 to 12 weeks' gestation. Time from insertion to removal of the speculum was significantly less with VA than D & C at 6 to 10 weeks' gestation but not at 11 to 12 weeks' gestation. Since vacuum aspiration is at least as safe as D & C, and appears to be more convenient and costeffective, it should on the basis of this experience be accepted over D & C as the standard method for treatment of first trimester abortion.", "contents": "A comparison of D & C and vacuum aspiration for performing first trimester abortion. In a study of techniques for first trimester abortion conducted at Kandang Kerbau Hospital in Singapore from September 1973 to April 1975, 420 physically healthy gravidas were randomly assigned to one of two treatment groups either by D & C or vacuum aspiration. Half of the patients in each group were 6 to 10 menstrual weeks' gestation and half were 11 to 12 week's gestation. The numbers of women with one or more complications were the same for the two treatment groups, but were significantly less when termination was carried out at 11 to 12 weeks' gestation. Estimated blood loss was significantly lower for patients treated by VA (32.3 ml) than for patients treated by D & C (39.0 ml) at 6 to 10 week's gestation, but the difference in blood loss was not statistically significant at 11 to 12 weeks' gestation. Time from insertion to removal of the speculum was significantly less with VA than D & C at 6 to 10 weeks' gestation but not at 11 to 12 weeks' gestation. Since vacuum aspiration is at least as safe as D & C, and appears to be more convenient and costeffective, it should on the basis of this experience be accepted over D & C as the standard method for treatment of first trimester abortion."}
{"id": "PMID:20345", "title": "Female sterilization using the tubal ring.", "content": "The surgical and early postoperative complications were evaluated in a study of 221 laparoscopies and 29 minilaparotomies in which tubal occlusions were performed with the application of tubal rings. For either procedure, complications were infrequent. None of the procedures had to be completed by another technique of tubal occlusion, and none of the patients required an extended hospitalization for the treatment of a complication. Among the 79 patients who have been followed up for more than 6 months, no pregnancies have been reported. The tubal ring technique appears to be safe and effective when used with either laparoscopy of minilaparotomy.", "contents": "Female sterilization using the tubal ring. The surgical and early postoperative complications were evaluated in a study of 221 laparoscopies and 29 minilaparotomies in which tubal occlusions were performed with the application of tubal rings. For either procedure, complications were infrequent. None of the procedures had to be completed by another technique of tubal occlusion, and none of the patients required an extended hospitalization for the treatment of a complication. Among the 79 patients who have been followed up for more than 6 months, no pregnancies have been reported. The tubal ring technique appears to be safe and effective when used with either laparoscopy of minilaparotomy."}
{"id": "PMID:20346", "title": "Contraceptive efficacy of two different metals using a modified seven vector.", "content": "Early studies with copper suggested that few improvements in overall IUD performance could be obtained with the use of more than 200 mm2 of copper. Thus, the use of other metals paired with copper has been investigated. This report of two studies of the small Copper-7, one with zinc and the other with copper alone, suggests that the addition of zinc in the superior position of the small Cu-7 decreases the incidence of pregnancy and that the small Cu-7 may be associated with higher retention rates than the standard Cu-7.", "contents": "Contraceptive efficacy of two different metals using a modified seven vector. Early studies with copper suggested that few improvements in overall IUD performance could be obtained with the use of more than 200 mm2 of copper. Thus, the use of other metals paired with copper has been investigated. This report of two studies of the small Copper-7, one with zinc and the other with copper alone, suggests that the addition of zinc in the superior position of the small Cu-7 decreases the incidence of pregnancy and that the small Cu-7 may be associated with higher retention rates than the standard Cu-7."}
{"id": "PMID:20347", "title": "The clinical efficacy of the repeated transcervical instillation of quinacrine for female sterilization.", "content": "The safety and efficacy of the repeated transcervical instillation of quinacrine hydrochloride in a suspension of 5 ml of 2% Xylocaine was evaluated in 200 patients. All instillation procedures were performed during the proliferative phase of the menstrual cycle: the second instillation was made in the first menstrual cycle following the initial instillation and the third and last instillation at 6 months after the first. None of the patients used any adjunctive contraceptives. Follow-up visits were scheduled at 6-month intervals after the last instillation. The potentially serious complications following the instillation were four cases of cortical exitation, and one case of acute adnexitis. The second instillation was not performed for 16.0% and the third instillation was not performed for 16.7% of the patients, for medical and/or personal reasons. Fifty-one pregnancies were reported, 41 (80.4%) before completion of the three instillations. The results of this study show that the instillation schedule used is unsatisfactory for widespread use. Additional studies are currently being conducted to evaluate the use of an adjunctive contraceptive up to the time of the third instillation in order to reduce the high pregnancy rate.", "contents": "The clinical efficacy of the repeated transcervical instillation of quinacrine for female sterilization. The safety and efficacy of the repeated transcervical instillation of quinacrine hydrochloride in a suspension of 5 ml of 2% Xylocaine was evaluated in 200 patients. All instillation procedures were performed during the proliferative phase of the menstrual cycle: the second instillation was made in the first menstrual cycle following the initial instillation and the third and last instillation at 6 months after the first. None of the patients used any adjunctive contraceptives. Follow-up visits were scheduled at 6-month intervals after the last instillation. The potentially serious complications following the instillation were four cases of cortical exitation, and one case of acute adnexitis. The second instillation was not performed for 16.0% and the third instillation was not performed for 16.7% of the patients, for medical and/or personal reasons. Fifty-one pregnancies were reported, 41 (80.4%) before completion of the three instillations. The results of this study show that the instillation schedule used is unsatisfactory for widespread use. Additional studies are currently being conducted to evaluate the use of an adjunctive contraceptive up to the time of the third instillation in order to reduce the high pregnancy rate."}
{"id": "PMID:20348", "title": "Fetal heart rate response to maternal hypotension during amniocentesis.", "content": "Ten cases of severe fetal heart rate deceleration following maternal vaso-vagal reflex during amniocentesis were presented. The good outcome of these fetuses suggests that this transient phenomenon has no adverse effect on the fetus. This type of FHR response should be recognized so as to avoid unnecessary Caesarian sections done because of severe FHR bradycardia following amniocentesis.", "contents": "Fetal heart rate response to maternal hypotension during amniocentesis. Ten cases of severe fetal heart rate deceleration following maternal vaso-vagal reflex during amniocentesis were presented. The good outcome of these fetuses suggests that this transient phenomenon has no adverse effect on the fetus. This type of FHR response should be recognized so as to avoid unnecessary Caesarian sections done because of severe FHR bradycardia following amniocentesis."}
{"id": "PMID:20349", "title": "Non-acceptance of puerperal sterilization. A study.", "content": "This is an analysis of reasons given by 800 women who were hospitalized for deliveries at the Government Kilpauk Medical College Hospital in Madras for refusing puerperal sterilization. The cases are analysed by socio-demographic characteristics, age and parity. The most common reasons given were \"inability to do manual work after the operation\", \"husband objects\", and \"necessity for prolonged rest\". The author suggests ways of dealing with these barriers to sterilization.", "contents": "Non-acceptance of puerperal sterilization. A study. This is an analysis of reasons given by 800 women who were hospitalized for deliveries at the Government Kilpauk Medical College Hospital in Madras for refusing puerperal sterilization. The cases are analysed by socio-demographic characteristics, age and parity. The most common reasons given were \"inability to do manual work after the operation\", \"husband objects\", and \"necessity for prolonged rest\". The author suggests ways of dealing with these barriers to sterilization."}
{"id": "PMID:20350", "title": "Uterine rupture and vacuum extraction.", "content": "Eleven uterine ruptures occurred among 11415 vacuum extractions, and these cases are analysed. Cervical tears extending into the lower uterine segment or into the broad ligament occurred in 4 cases, lower segment tears in 6 and a fundal tear in 1. One patient died of respiratory failure. The possible cause of uterine rupture with vacuum extraction appear to be a combination of an unengaged fetal head, an incompletely dilated cervix and an undetected mild cephalopelvic disproportion especially in grandmultiparae, dehiscent or weak uterine scars, prolonged traction without progress, manipulations in shoulder dystocia and obstruction and excessive non controlled traction. Uterine rupture can be minimized by careful selection of cases, proper technique and early recognition of failure.", "contents": "Uterine rupture and vacuum extraction. Eleven uterine ruptures occurred among 11415 vacuum extractions, and these cases are analysed. Cervical tears extending into the lower uterine segment or into the broad ligament occurred in 4 cases, lower segment tears in 6 and a fundal tear in 1. One patient died of respiratory failure. The possible cause of uterine rupture with vacuum extraction appear to be a combination of an unengaged fetal head, an incompletely dilated cervix and an undetected mild cephalopelvic disproportion especially in grandmultiparae, dehiscent or weak uterine scars, prolonged traction without progress, manipulations in shoulder dystocia and obstruction and excessive non controlled traction. Uterine rupture can be minimized by careful selection of cases, proper technique and early recognition of failure."}
{"id": "PMID:20351", "title": "The use of the ultrasonic echo technique in examining the normal and pathological involution in the puerperium.", "content": "The involution of the uterus in the puerperium was investigated after 50 normal, and 15 pathological pregnancies. By means of daily performed ultrasonic examinations the size and location of the uterus can be well determined, and the pace of the involution as well as the existing subinvolution can be diagnosed. It was found that in multiparas and in cases of uterine malformations the pace of the involution is somewhat slower, while in premature deliveries it is faster. By the help of this harmless and repeatable diagnostic technique the puerperal complications can be recognized and thus prevented.", "contents": "The use of the ultrasonic echo technique in examining the normal and pathological involution in the puerperium. The involution of the uterus in the puerperium was investigated after 50 normal, and 15 pathological pregnancies. By means of daily performed ultrasonic examinations the size and location of the uterus can be well determined, and the pace of the involution as well as the existing subinvolution can be diagnosed. It was found that in multiparas and in cases of uterine malformations the pace of the involution is somewhat slower, while in premature deliveries it is faster. By the help of this harmless and repeatable diagnostic technique the puerperal complications can be recognized and thus prevented."}
{"id": "PMID:20352", "title": "Induced illegal abortions in Benin City, Nigeria.", "content": "Abortions of all types constitute about 25% of our gynaecological admissions. In 8 months period between July 1974 and February 1975, 59 patients admitted into our unit with confirmed illegally induced abortions were studied personally by the author. It was found that most patients with this type of abortion were single, young schoolgirls. Most of the patients were 12 weeks pregnant or more at the time of the attempted termination. Most of the people who carried out these 'operations' by instrumentation were usually unskilled personnel. The complications in these patients which included one death are discussed. It is concluded that sex education including the use of contraceptive devices will help in reducing the high incidence of this 'social evil'. It is also thought that the liberalization of abortion laws in this country will also be helpful in reducing the complications associated with induced abortions.", "contents": "Induced illegal abortions in Benin City, Nigeria. Abortions of all types constitute about 25% of our gynaecological admissions. In 8 months period between July 1974 and February 1975, 59 patients admitted into our unit with confirmed illegally induced abortions were studied personally by the author. It was found that most patients with this type of abortion were single, young schoolgirls. Most of the patients were 12 weeks pregnant or more at the time of the attempted termination. Most of the people who carried out these 'operations' by instrumentation were usually unskilled personnel. The complications in these patients which included one death are discussed. It is concluded that sex education including the use of contraceptive devices will help in reducing the high incidence of this 'social evil'. It is also thought that the liberalization of abortion laws in this country will also be helpful in reducing the complications associated with induced abortions."}
{"id": "PMID:20353", "title": "Human chorionic somatomammotropin in normal pregnancy in an Asian population.", "content": "Serial Human Chorionic Somatomammotropin (HCS) levels were measured during the last 10 weeks of pregnancy in 57 patients (375 samples). There was a gradual rise from 5.6 microgram/ml at the 30th week to microgram/ml at the 40th week, with a plateau during the last 4 weeks of pregnancy. No correlation could be found of HCS levels with parity, maternal age, maternal height, maternal weight, foetal weight and foetal sex. A weak but significant relationship was found between HCS and plasma oestriol (r = 2.4, p less than 0.001).", "contents": "Human chorionic somatomammotropin in normal pregnancy in an Asian population. Serial Human Chorionic Somatomammotropin (HCS) levels were measured during the last 10 weeks of pregnancy in 57 patients (375 samples). There was a gradual rise from 5.6 microgram/ml at the 30th week to microgram/ml at the 40th week, with a plateau during the last 4 weeks of pregnancy. No correlation could be found of HCS levels with parity, maternal age, maternal height, maternal weight, foetal weight and foetal sex. A weak but significant relationship was found between HCS and plasma oestriol (r = 2.4, p less than 0.001)."}
{"id": "PMID:20354", "title": "Fetal heart rate and fetal movements.", "content": "Fetal Heart Rate (F.H.R.) in association with fetal movement was evaluated in 141 normal and pathological pregnancies. In the normal cases only 31% showed an acceleration of F.H.R. in association with fetal movement. The majority of the normal cases, 62%, did not demonstrate changes in F.H.R. in association with fetal movement. In the pathological pregnancies there were no characteristic changes in F.H.R. associated with fetal movement. It appears that F.H.R. acceleration associated with fetal movement cannot be used as an index for fetal well being.", "contents": "Fetal heart rate and fetal movements. Fetal Heart Rate (F.H.R.) in association with fetal movement was evaluated in 141 normal and pathological pregnancies. In the normal cases only 31% showed an acceleration of F.H.R. in association with fetal movement. The majority of the normal cases, 62%, did not demonstrate changes in F.H.R. in association with fetal movement. In the pathological pregnancies there were no characteristic changes in F.H.R. associated with fetal movement. It appears that F.H.R. acceleration associated with fetal movement cannot be used as an index for fetal well being."}
{"id": "PMID:20355", "title": "Iron deficiency anaemia in a rural area in Nigeria. Evaluation of diagnosis and treatment with imferon.", "content": "In 32 pregnant women with packed cell volume (PCV) of 30% or less (Hb 10 g/100 ml or below), iron depletion was present in 87.5% and megaloblastic changes in 84.5% as judged by bone marrow findings. Parenteral iron gave statistically significant rise in the PCV (p less than 0.001) in those who received iron therapy compared with control group with no iron therapy. Routine iron administration during pregnancy is therefore indicated in this population.", "contents": "Iron deficiency anaemia in a rural area in Nigeria. Evaluation of diagnosis and treatment with imferon. In 32 pregnant women with packed cell volume (PCV) of 30% or less (Hb 10 g/100 ml or below), iron depletion was present in 87.5% and megaloblastic changes in 84.5% as judged by bone marrow findings. Parenteral iron gave statistically significant rise in the PCV (p less than 0.001) in those who received iron therapy compared with control group with no iron therapy. Routine iron administration during pregnancy is therefore indicated in this population."}
{"id": "PMID:20356", "title": "Acute carcinomatous myopathy associated with ovarian carcinoma.", "content": "A case of acute, fatal, rapidly progressive pure myopathy associated with ovarian carcinoma is described. The first symptoms of carcinomatous myopathy occurred 8 months after surgical treatment and combined chemotherapy. The patient died 2 months after onset of myopathy. The clinical and pathologic findings of the myopathy are discussed.", "contents": "Acute carcinomatous myopathy associated with ovarian carcinoma. A case of acute, fatal, rapidly progressive pure myopathy associated with ovarian carcinoma is described. The first symptoms of carcinomatous myopathy occurred 8 months after surgical treatment and combined chemotherapy. The patient died 2 months after onset of myopathy. The clinical and pathologic findings of the myopathy are discussed."}
{"id": "PMID:20357", "title": "The effect of miconazole on vulvo-vaginal candidosis in pregnant and non-pregnant women and their partners.", "content": "Miconazole cream (Daktar vaginal cream 2%, Leo) given for 12-14 days was tested in 85 subjects with positive vaginal candida culture. Eighty percent of the patients were pregnant. Healing was observed in 93% of the cases. Treatment of the sexual partner did not influence the therapeutic effect.", "contents": "The effect of miconazole on vulvo-vaginal candidosis in pregnant and non-pregnant women and their partners. Miconazole cream (Daktar vaginal cream 2%, Leo) given for 12-14 days was tested in 85 subjects with positive vaginal candida culture. Eighty percent of the patients were pregnant. Healing was observed in 93% of the cases. Treatment of the sexual partner did not influence the therapeutic effect."}
{"id": "PMID:20358", "title": "Use of prostaglandin F2alpha in the management of missed abortion.", "content": "Intravenous infusion of PG F2alpha was used to induce uterine contractions in 9 cases of missed abortions. Except for one case which was an extra uterine pregnancy, all of the patients aborted successfully. There were no major complications. The use of PG is suggested as a method of choice in the management of missed abortion specially in the second trimester.", "contents": "Use of prostaglandin F2alpha in the management of missed abortion. Intravenous infusion of PG F2alpha was used to induce uterine contractions in 9 cases of missed abortions. Except for one case which was an extra uterine pregnancy, all of the patients aborted successfully. There were no major complications. The use of PG is suggested as a method of choice in the management of missed abortion specially in the second trimester."}
{"id": "PMID:20359", "title": "Transplacental passage of diazepam following intravenous injection immediately prior to operative vaginal delivery.", "content": "The early phase of diaplacental transfer of diazepam was studied in 39 women given the drug as a basic anaesthetic for operative vaginal delivery indicated by prolonged second stage of labour (9 cases), breech delivery (19 cases) and intrauterine hypoxia (11 cases). A total dose of 30 mg diazepam (Valium Roche) was injected intravenously over a period of 15 sec umbilical cord blood was collected immediately after delivery. Diazepam was extracted with diethyl ether and determined by gas chromatography. The concentration of diazepam in cord blood increased from greater than 5-250 ng/ml at 57-60 seconds to 48-1861 ng/ml at 90-100 seconds after completion of the intravenous injection. Thereafter a plateau seemed to be reached but the interindividual variation was still great with values ranging from 45-3034 ng/ml up to 360 seconds. Judged by Apgar score and the clinical course the neonates seemed to be unaffected by the medication administered to the mother.", "contents": "Transplacental passage of diazepam following intravenous injection immediately prior to operative vaginal delivery. The early phase of diaplacental transfer of diazepam was studied in 39 women given the drug as a basic anaesthetic for operative vaginal delivery indicated by prolonged second stage of labour (9 cases), breech delivery (19 cases) and intrauterine hypoxia (11 cases). A total dose of 30 mg diazepam (Valium Roche) was injected intravenously over a period of 15 sec umbilical cord blood was collected immediately after delivery. Diazepam was extracted with diethyl ether and determined by gas chromatography. The concentration of diazepam in cord blood increased from greater than 5-250 ng/ml at 57-60 seconds to 48-1861 ng/ml at 90-100 seconds after completion of the intravenous injection. Thereafter a plateau seemed to be reached but the interindividual variation was still great with values ranging from 45-3034 ng/ml up to 360 seconds. Judged by Apgar score and the clinical course the neonates seemed to be unaffected by the medication administered to the mother."}
{"id": "PMID:20360", "title": "Serum naphythylamidase isoenzymes during hormonal treatment. Electrophoretic and quantitative studies.", "content": "Alterations in serum naphthylamidase isoenzymes were studied by electrophoretic and quantitative methods in women treated with oral contraceptives and women treated with naturally occurring conjugated estrogens for climacteric symptoms. In women treated with oral contraceptives the appearance of extra isoenzyme components was accompanied by a distinct and significant increase in the total serum naphthylamidase activity, whereas in treatment with conjugated estrogens no such increase was found. The result suggests that combined oral contraceptives and natural estrogens affect the serum naphthylamidase pattern in different ways.", "contents": "Serum naphythylamidase isoenzymes during hormonal treatment. Electrophoretic and quantitative studies. Alterations in serum naphthylamidase isoenzymes were studied by electrophoretic and quantitative methods in women treated with oral contraceptives and women treated with naturally occurring conjugated estrogens for climacteric symptoms. In women treated with oral contraceptives the appearance of extra isoenzyme components was accompanied by a distinct and significant increase in the total serum naphthylamidase activity, whereas in treatment with conjugated estrogens no such increase was found. The result suggests that combined oral contraceptives and natural estrogens affect the serum naphthylamidase pattern in different ways."}
{"id": "PMID:20361", "title": "Homotransplantation of the amniotic membrane for the treatment of congenital absence of the vagina.", "content": "Homotransplantation of the amniotic membrane for the treatment of congenital absence of the vagina is described. Two years' follow-up with biopsy specimens revealed that amniotic membrane cells divide mitotically and activate vaginal epithelial proliferation of the squamous type and which respond to exogenous estrogens.", "contents": "Homotransplantation of the amniotic membrane for the treatment of congenital absence of the vagina. Homotransplantation of the amniotic membrane for the treatment of congenital absence of the vagina is described. Two years' follow-up with biopsy specimens revealed that amniotic membrane cells divide mitotically and activate vaginal epithelial proliferation of the squamous type and which respond to exogenous estrogens."}
{"id": "PMID:20362", "title": "Perforation of the uterus by copper-IUDs.", "content": "In about 5 000 copper-IUD insertions 5 cases of perforation were found. One woman had 2 devices inserted, both of them perforated. Copper-T was responsible for 3 corporal perforations and copper-7 for 2 corporal and 1 cervical perforation.", "contents": "Perforation of the uterus by copper-IUDs. In about 5 000 copper-IUD insertions 5 cases of perforation were found. One woman had 2 devices inserted, both of them perforated. Copper-T was responsible for 3 corporal perforations and copper-7 for 2 corporal and 1 cervical perforation."}
{"id": "PMID:20363", "title": "Twins, immuno-incompatibility and pre-eclampsia.", "content": "A survey of 417 twin pregnancies is reported. Examination of the data revealed no difference in the incidence of pre-eclampsia referable to the zygosity of the twins. The findings thus lends no support to the hypothesis that immuno-incompatibility contributes to the aetiology of pre-eclampsia.", "contents": "Twins, immuno-incompatibility and pre-eclampsia. A survey of 417 twin pregnancies is reported. Examination of the data revealed no difference in the incidence of pre-eclampsia referable to the zygosity of the twins. The findings thus lends no support to the hypothesis that immuno-incompatibility contributes to the aetiology of pre-eclampsia."}
{"id": "PMID:20366", "title": "Calcified myoma of utero-ovarian ligament in a pubertal girl.", "content": "A calcified myoma of the utero-ovarian ligament was encountered in a 13-year-old girl. The age of the patient and the unusual location prompt this report of a possibly unique entity, and the pertinent literature is cited.", "contents": "Calcified myoma of utero-ovarian ligament in a pubertal girl. A calcified myoma of the utero-ovarian ligament was encountered in a 13-year-old girl. The age of the patient and the unusual location prompt this report of a possibly unique entity, and the pertinent literature is cited."}
{"id": "PMID:20384", "title": "An enzymatic time/temperature device for monitoring the handling of perishable commodities.", "content": "Kockums Chemical AB, Malm\u00f6, Sweden, has developed a biochemical indicator, the i-point TTM (Time-Temperature Monitor). The indicator responds to temperature in much the same way as perishable commodities in which loss of quality is directly related to the combined effects of the degree and the duration of storage temperature. Primary application of such indicators are expected for frozen, refrigerated and fresh food products. The device can be useful in monitoring the handling of various temperature sensitive noon-food products as well. Reacting at a relatively low rate under optimum temperture conditions and at accelerated rates as temperature rises, the indicator chemically integrates and accumulates both the length and degree of all temperature experiences. When pre-selected time-temperature limits have been exceeded a distinct irreversible color change will occur, indicating that action is required--the particular depending upon  the use being made of the commodity.", "contents": "An enzymatic time/temperature device for monitoring the handling of perishable commodities. Kockums Chemical AB, Malm\u00f6, Sweden, has developed a biochemical indicator, the i-point TTM (Time-Temperature Monitor). The indicator responds to temperature in much the same way as perishable commodities in which loss of quality is directly related to the combined effects of the degree and the duration of storage temperature. Primary application of such indicators are expected for frozen, refrigerated and fresh food products. The device can be useful in monitoring the handling of various temperature sensitive noon-food products as well. Reacting at a relatively low rate under optimum temperture conditions and at accelerated rates as temperature rises, the indicator chemically integrates and accumulates both the length and degree of all temperature experiences. When pre-selected time-temperature limits have been exceeded a distinct irreversible color change will occur, indicating that action is required--the particular depending upon  the use being made of the commodity."}
{"id": "PMID:20385", "title": "Interrelationships between histamine, prostaglandins, and cyclic AMP in gastric secretion: a hypothesis.", "content": "Based on the current experimental evidence, a model is proposed for mutual interactions of histamine, prostaglandins, and cyclic AMP in regulation of gastric secretion and pathogenesis of peptic ulcer. Histamine acting on H2-receptor-associated adenylate cyclase stimulates cyclic AMP formation and consequently secretion of hydrochloric acid in oxyntic cells. Prostaglandins (mainly E type) in another cell population stimulate cyclic AMP formation which may lead to formation of glycosaminoglycans and glycoproteins. Glycosaminoglycans and glycoproteins may have antisecretory and cytoprotective properties. In addition to this effect, prostaglandin endoperoxides may inhibit histamine-stimulated cyclic AMP formation in oxyntic cells.", "contents": "Interrelationships between histamine, prostaglandins, and cyclic AMP in gastric secretion: a hypothesis. Based on the current experimental evidence, a model is proposed for mutual interactions of histamine, prostaglandins, and cyclic AMP in regulation of gastric secretion and pathogenesis of peptic ulcer. Histamine acting on H2-receptor-associated adenylate cyclase stimulates cyclic AMP formation and consequently secretion of hydrochloric acid in oxyntic cells. Prostaglandins (mainly E type) in another cell population stimulate cyclic AMP formation which may lead to formation of glycosaminoglycans and glycoproteins. Glycosaminoglycans and glycoproteins may have antisecretory and cytoprotective properties. In addition to this effect, prostaglandin endoperoxides may inhibit histamine-stimulated cyclic AMP formation in oxyntic cells."}
{"id": "PMID:20386", "title": "Gastric adenosine triphosphatases: a review of their possible role in HCl secretion.", "content": "In the search for gastric ATPases that might be related to the mechanism of HCl secretion, an interesting and rather unique K+-stimulated ATPase has been discovered. This enzyme is isolated from oxyntic cells and has been associated with the apical plasma membrane and/or tubulovesicular system. Membrane vesicles containing the K+-stimulated ATPase transport H+ into the vesicular lumen under the appropriate conditions of ATP, Mg2+, and KCl. This process can be measured by pH electrode, binding of certain metachromatic dyes to \"energized\" sites, or accumulation ratios of substances with appropriate pK values. Vesicular interior can be acidified to pH 3.5 or below. At the present time, it is difficult to distinguish between an electrogenic H+ pump and an electroneutral H+/K+ exchange mechanism. A hypothetical scheme for the gastric H+ secretory mechanism is proposed which fits much of the data from studies on the K+-ATPase, vesicular transport, and intact gastric mucosa.", "contents": "Gastric adenosine triphosphatases: a review of their possible role in HCl secretion. In the search for gastric ATPases that might be related to the mechanism of HCl secretion, an interesting and rather unique K+-stimulated ATPase has been discovered. This enzyme is isolated from oxyntic cells and has been associated with the apical plasma membrane and/or tubulovesicular system. Membrane vesicles containing the K+-stimulated ATPase transport H+ into the vesicular lumen under the appropriate conditions of ATP, Mg2+, and KCl. This process can be measured by pH electrode, binding of certain metachromatic dyes to \"energized\" sites, or accumulation ratios of substances with appropriate pK values. Vesicular interior can be acidified to pH 3.5 or below. At the present time, it is difficult to distinguish between an electrogenic H+ pump and an electroneutral H+/K+ exchange mechanism. A hypothetical scheme for the gastric H+ secretory mechanism is proposed which fits much of the data from studies on the K+-ATPase, vesicular transport, and intact gastric mucosa."}
{"id": "PMID:20387", "title": "Electrical events during activation and inhibition of gastric HCl secretion.", "content": "A brief review of some of the relationships between the secretory rate and the electrophysiological characteristics of the canine and frog gastric mucosa is presented. There is no simple relationship between the potential difference (PD) and H+ rate in the in vitro frog gastric mucosa with standard Cl- bathing solutions. In contrast, with Cl- -free solutions (PD is inverted) there is a precise linear relationship between the PD and the H+ rate. This linear relationship is strong support for the concept that the H+ mechanism under these conditions is electrogenic. In the past it has been difficult rigorously to exclude the possibility that the inverted PD is due to a liquid junction potential between acid fluid in the lumina and the secretory bathing solution. Use of aminopyrine or imidazole essentially eliminates the possibility that the inverted PD is due to a liquid junction potential. Hence the linear relationship is solid evidence for the electrogenicity of the H+ mechanism. Recently we have shown that aminopyrine or imidazole can reverse thiocyanate inhibition of H+ secretion.", "contents": "Electrical events during activation and inhibition of gastric HCl secretion. A brief review of some of the relationships between the secretory rate and the electrophysiological characteristics of the canine and frog gastric mucosa is presented. There is no simple relationship between the potential difference (PD) and H+ rate in the in vitro frog gastric mucosa with standard Cl- bathing solutions. In contrast, with Cl- -free solutions (PD is inverted) there is a precise linear relationship between the PD and the H+ rate. This linear relationship is strong support for the concept that the H+ mechanism under these conditions is electrogenic. In the past it has been difficult rigorously to exclude the possibility that the inverted PD is due to a liquid junction potential between acid fluid in the lumina and the secretory bathing solution. Use of aminopyrine or imidazole essentially eliminates the possibility that the inverted PD is due to a liquid junction potential. Hence the linear relationship is solid evidence for the electrogenicity of the H+ mechanism. Recently we have shown that aminopyrine or imidazole can reverse thiocyanate inhibition of H+ secretion."}
{"id": "PMID:20392", "title": "[Drug effects on blood pressure and heart rate in unanesthetized animals. (1). Effects of beta-blocking agents (author's transl)].", "content": "beta-Blocking actions of orally administered K\u00f6 1400 and tiprenolol, new beta-blocking agents, were studied in unanesthetized rats and dogs, using a fall of blood pressure and an increase in heart rate produced by isoproterenol as a measure of beta-receptor activation. Blood pressure was recorded from the aorta of the dog and the caudal artery of rat via indwelling catheter, and heart rate of the dog was recorded by a cardiotachometer triggered by R waves of the lead II electrocardiogram. Mean resting blood pressure was 116 mmHg in rats and 93 mmHg in dogs, and heart rate was 99 beats/min in dogs. Isoproterenol (0.5 microgram/kg) was injected via indwelling venous catheter. K\u00f6 1400, tiprenolol and propranolol inhibited the hypotension and tachycardia induced by isoproterenol at an oral dose level of 2 mg/kg or more. beta-blocking action in these preparations was found to be tiprenolol greater than K\u00f6 1400 greater than propranolol. Pharmacological half life of tiprenolol was longer than that of propranolol, whereas that of K\u00f6 1400 was shorter. No selectivity of beta-blocking actions was observed with all three beta-blockers. These findings are in agreement with the results obtained in isolated atrial and tracheal preparations of the guinea pig.", "contents": "[Drug effects on blood pressure and heart rate in unanesthetized animals. (1). Effects of beta-blocking agents (author's transl)]. beta-Blocking actions of orally administered K\u00f6 1400 and tiprenolol, new beta-blocking agents, were studied in unanesthetized rats and dogs, using a fall of blood pressure and an increase in heart rate produced by isoproterenol as a measure of beta-receptor activation. Blood pressure was recorded from the aorta of the dog and the caudal artery of rat via indwelling catheter, and heart rate of the dog was recorded by a cardiotachometer triggered by R waves of the lead II electrocardiogram. Mean resting blood pressure was 116 mmHg in rats and 93 mmHg in dogs, and heart rate was 99 beats/min in dogs. Isoproterenol (0.5 microgram/kg) was injected via indwelling venous catheter. K\u00f6 1400, tiprenolol and propranolol inhibited the hypotension and tachycardia induced by isoproterenol at an oral dose level of 2 mg/kg or more. beta-blocking action in these preparations was found to be tiprenolol greater than K\u00f6 1400 greater than propranolol. Pharmacological half life of tiprenolol was longer than that of propranolol, whereas that of K\u00f6 1400 was shorter. No selectivity of beta-blocking actions was observed with all three beta-blockers. These findings are in agreement with the results obtained in isolated atrial and tracheal preparations of the guinea pig."}
{"id": "PMID:20393", "title": "[Effects of a new adrenergic beta-blocking agent, K\u00f6 1400 on the canine heart-lung preparation supported by a donor dog and the perfused hindlimb preparation of the dog (author's transl)].", "content": "Using the canine heart-lung preparation supported by a donor, effects of a new adrenergic beta-blocking agent, dl-1-(tert. butylamino)-3-[ (2-propinyloxy) phenoxy]-2-propanol hydrochloride (K\u00f6 1400), on cardiac function, myocardial metabolism, and coronary circulation were studied and compared with those of propranolol. Effects of this substance on the peripheral vascular bed were also studied in the perfused hindlimb preparation of the dog. K\u00f6 1400 produced a positive inotropic and chronotropic effect. Mechanical efficiency of the heart improved after K\u00f6 1400, while it lessened after propranolol. A decrease in the coronary flow was observed in association with a slight increase in myocardial O2 consumption, indicating that the substance exerted a direct constrictive effect on the coronary vasculature. As a beta-blocker, K\u00f6 1400 was found to be 2-3 times more effective than propranolol. The uptake of the free fatty acid (FFA) by the heart was increased by K\u00f6 1400 and the myocardial redox potential improved. In the perfused hindlimb preparation, intraarterial injection of K\u00f6 1400 resulted in a transient increase of the femoral blood flow for a decrease in the flow followed by a sustained decrease. With repeated administration a marked tachyphylaxis was observed.", "contents": "[Effects of a new adrenergic beta-blocking agent, K\u00f6 1400 on the canine heart-lung preparation supported by a donor dog and the perfused hindlimb preparation of the dog (author's transl)]. Using the canine heart-lung preparation supported by a donor, effects of a new adrenergic beta-blocking agent, dl-1-(tert. butylamino)-3-[ (2-propinyloxy) phenoxy]-2-propanol hydrochloride (K\u00f6 1400), on cardiac function, myocardial metabolism, and coronary circulation were studied and compared with those of propranolol. Effects of this substance on the peripheral vascular bed were also studied in the perfused hindlimb preparation of the dog. K\u00f6 1400 produced a positive inotropic and chronotropic effect. Mechanical efficiency of the heart improved after K\u00f6 1400, while it lessened after propranolol. A decrease in the coronary flow was observed in association with a slight increase in myocardial O2 consumption, indicating that the substance exerted a direct constrictive effect on the coronary vasculature. As a beta-blocker, K\u00f6 1400 was found to be 2-3 times more effective than propranolol. The uptake of the free fatty acid (FFA) by the heart was increased by K\u00f6 1400 and the myocardial redox potential improved. In the perfused hindlimb preparation, intraarterial injection of K\u00f6 1400 resulted in a transient increase of the femoral blood flow for a decrease in the flow followed by a sustained decrease. With repeated administration a marked tachyphylaxis was observed."}
{"id": "PMID:20395", "title": "[Studies on gamma-oryzanol. III. Influence of gamma-oryzanol on circadian rhythms of serum gastrin, 11-OHCS and gastric secretion in rats (author's transl)].", "content": "In the course of investigations of gamma-oryzanol in rats, circadian rhythms in antiulcerogenic action on gamma-oryzanol were observed. Circadian rhythms in several other parameters were investigated and correlated with the antiulcerogenic action. Pretreatment of rats with gamma-oryzanol 100 mg/kg, s.c., for 5 days tended to decrease serum gastrin levels and gastric secretion, and to increase serum 11-OHCS. Suppresive patterns of serum gastrin and gastric secretion following the pretreatment with gamma-oryzanol corresponded to the circadian rhythms in antiulcerogenic action of gamma-oryzanol. A complication of our results suggests that increment of catecholamines in rat brain after gamma-oryzanol plays a role in the above mentioned actions.", "contents": "[Studies on gamma-oryzanol. III. Influence of gamma-oryzanol on circadian rhythms of serum gastrin, 11-OHCS and gastric secretion in rats (author's transl)]. In the course of investigations of gamma-oryzanol in rats, circadian rhythms in antiulcerogenic action on gamma-oryzanol were observed. Circadian rhythms in several other parameters were investigated and correlated with the antiulcerogenic action. Pretreatment of rats with gamma-oryzanol 100 mg/kg, s.c., for 5 days tended to decrease serum gastrin levels and gastric secretion, and to increase serum 11-OHCS. Suppresive patterns of serum gastrin and gastric secretion following the pretreatment with gamma-oryzanol corresponded to the circadian rhythms in antiulcerogenic action of gamma-oryzanol. A complication of our results suggests that increment of catecholamines in rat brain after gamma-oryzanol plays a role in the above mentioned actions."}
{"id": "PMID:20396", "title": "[Comparative study between dobutamine and other catecholamines in their effects on the cardiac contraction and rhythm (author's transl)].", "content": "Dobutamine (DOB) showed a dose dependent positive introphic effect on the right ventricular muscle of vagotomized Beagle dogs under pentobarbital anesthesia. Positve inotropic effects of other catecholamines (CA) decreased in the following order; isoproterenol (Iso, 115) greater than norepinephrine (NE, 15) greater than DOB (1) greater than dopamine (DA, 0.36). Brachiocephalic arterial flow was also increased by DOB with a positive inotropic effect in the right ventricular muscle. Though the positive inotropic effect of DOB was slightly decreased by pretreatment with phenoxybenzamine, such was almost completely antagonized by propranolol. Contractions of isolated cat papillary muscle driven by electrical stimulation (12 beats/min) were increased by CA in the following order; Iso (17) greater than NE (3) greater than epinephrine (2.5) greater than DOB (1) greater than DA (1 greater than). Activity of DOB to induce spontaneous contractions of papillary muscle was weakest among these CA. To determine the arrhythmogenic effect of these CA, coronary ligated Beagle dogs were employed, in which the anterior descending branch of the left coronary artery was ligated. Arrhythmogenic activity of DOB was weaker than other CA employed both in early stages and 48 hr after coronary ligation. DOB shows good potential for treating acute cardiac insufficiency and cardiogenic shock, as effects on heart rate and blood pressure are weaker.", "contents": "[Comparative study between dobutamine and other catecholamines in their effects on the cardiac contraction and rhythm (author's transl)]. Dobutamine (DOB) showed a dose dependent positive introphic effect on the right ventricular muscle of vagotomized Beagle dogs under pentobarbital anesthesia. Positve inotropic effects of other catecholamines (CA) decreased in the following order; isoproterenol (Iso, 115) greater than norepinephrine (NE, 15) greater than DOB (1) greater than dopamine (DA, 0.36). Brachiocephalic arterial flow was also increased by DOB with a positive inotropic effect in the right ventricular muscle. Though the positive inotropic effect of DOB was slightly decreased by pretreatment with phenoxybenzamine, such was almost completely antagonized by propranolol. Contractions of isolated cat papillary muscle driven by electrical stimulation (12 beats/min) were increased by CA in the following order; Iso (17) greater than NE (3) greater than epinephrine (2.5) greater than DOB (1) greater than DA (1 greater than). Activity of DOB to induce spontaneous contractions of papillary muscle was weakest among these CA. To determine the arrhythmogenic effect of these CA, coronary ligated Beagle dogs were employed, in which the anterior descending branch of the left coronary artery was ligated. Arrhythmogenic activity of DOB was weaker than other CA employed both in early stages and 48 hr after coronary ligation. DOB shows good potential for treating acute cardiac insufficiency and cardiogenic shock, as effects on heart rate and blood pressure are weaker."}
{"id": "PMID:20398", "title": "[Clinical picture of lactate acidosis. 4: Clinical significance of lactate acidosis].", "content": "The diagnosis of lactate acidosis is complicated by the fact that lactate determination is not a routine method in clinical chemistry. In fact, lactate analysis is performed only in special laboratories. Even in greater clinics this method is not routinely performed in differential diagnosis of acidotic states. Various diseases are accompanied by a lactate emia or even by lactate acidosis. Anaerobic synthesis of lactate is an emergency reaction to supply minimum energy to tissues with insufficient oxygen supply. The main diseases complicated by increased blood lactate concentrations are shock, circulatory collapse, cardiac failure and peripheral circularoty disturbance. Additionally diabetes mellitus, septical infections, and-the most prominent situation-biguanide intoxications are complicated by an increase in blood lactate concentration.", "contents": "[Clinical picture of lactate acidosis. 4: Clinical significance of lactate acidosis]. The diagnosis of lactate acidosis is complicated by the fact that lactate determination is not a routine method in clinical chemistry. In fact, lactate analysis is performed only in special laboratories. Even in greater clinics this method is not routinely performed in differential diagnosis of acidotic states. Various diseases are accompanied by a lactate emia or even by lactate acidosis. Anaerobic synthesis of lactate is an emergency reaction to supply minimum energy to tissues with insufficient oxygen supply. The main diseases complicated by increased blood lactate concentrations are shock, circulatory collapse, cardiac failure and peripheral circularoty disturbance. Additionally diabetes mellitus, septical infections, and-the most prominent situation-biguanide intoxications are complicated by an increase in blood lactate concentration."}
{"id": "PMID:20399", "title": "Pathogenesis of cryptorchidism.", "content": "Cryptorchidism was induced experimentally by treating pregnant mice on the 14th day of pregnancy with 5 mg estrogen. Testes from cryptorchid and control newborn and adult mice were investigated with radioimmunoassay and electron microscopy. It was concluded that a normal Leydig cell function plays a decisive role in testicular descent. In cryptorchidism, Leydig cells at birth are atrophic. Testicular testosterone content is diminished as compared to controls. Ultrastructural alterations of Leydig cells observed in our experiments closely resemble those found in biopsies of cryptorchid patients. In male mouse offspring, prenatal estrogen injection induced not only a cryptorchidism but also Leydig cell atrophy and a permanently impaired function. Testosterone content is still significantly diminished after puberty. It is proposed therefore that an insufficiency of endocrine gonadal function of hypothalamo-pituitary origin occurring during intrauterine development is one of the main causes of cryptorchidism. An appropriate long-term therapy could diminish the high sterility rate.", "contents": "Pathogenesis of cryptorchidism. Cryptorchidism was induced experimentally by treating pregnant mice on the 14th day of pregnancy with 5 mg estrogen. Testes from cryptorchid and control newborn and adult mice were investigated with radioimmunoassay and electron microscopy. It was concluded that a normal Leydig cell function plays a decisive role in testicular descent. In cryptorchidism, Leydig cells at birth are atrophic. Testicular testosterone content is diminished as compared to controls. Ultrastructural alterations of Leydig cells observed in our experiments closely resemble those found in biopsies of cryptorchid patients. In male mouse offspring, prenatal estrogen injection induced not only a cryptorchidism but also Leydig cell atrophy and a permanently impaired function. Testosterone content is still significantly diminished after puberty. It is proposed therefore that an insufficiency of endocrine gonadal function of hypothalamo-pituitary origin occurring during intrauterine development is one of the main causes of cryptorchidism. An appropriate long-term therapy could diminish the high sterility rate."}
{"id": "PMID:20400", "title": "The use of luteinizing hormone-releasing hormone in pediatric patients.", "content": "Luteinizing hormone-releasing hormone (LH-RH), first synthetized in 1971; became soon available for clinical purposes and was immediately used as a diagnostic tool in children and adolescents as well as in adults. The first results of the LH-RH test in pediatrics were reported in 1972 and soon after discussed in meetings allowing comparison of the data from different groups. From this time, a great number of publications has been devoted to the diagnostic usefulness of LH-RH in the study of pubertal development and of pituitary-gonadal disorders in children and adolescents. Until recently, the theraeputic use of LH-RH has been restricted by the lack of availability of sufficient amounts, so that only few preliminary data have been reported in this field. Thus the scope of this review is mainly to present a critical survey of the data concerning LH-RH test in pediatric patients.", "contents": "The use of luteinizing hormone-releasing hormone in pediatric patients. Luteinizing hormone-releasing hormone (LH-RH), first synthetized in 1971; became soon available for clinical purposes and was immediately used as a diagnostic tool in children and adolescents as well as in adults. The first results of the LH-RH test in pediatrics were reported in 1972 and soon after discussed in meetings allowing comparison of the data from different groups. From this time, a great number of publications has been devoted to the diagnostic usefulness of LH-RH in the study of pubertal development and of pituitary-gonadal disorders in children and adolescents. Until recently, the theraeputic use of LH-RH has been restricted by the lack of availability of sufficient amounts, so that only few preliminary data have been reported in this field. Thus the scope of this review is mainly to present a critical survey of the data concerning LH-RH test in pediatric patients."}
{"id": "PMID:20403", "title": "Differences in mouse interferons according to cell source and mode of induction.", "content": "Mouse interferon induced by ultraviolet-irradiated Newcastle disease virus or polyriboinosinic-polyribocytidylic acid in T lymphocytes, B lymphocytes, macrophages, and primary mouse embryonic cell culture was studied. Irrespective of the inducer, interferons produced by T or B lymphocytes were relatively heat stable and of low antigenicity when reacted with antiserum against L-cell interferon (ALI), whereas interferons produced by macrophages and mouse embryo cells were heat labile and of high antigenicity against ALI. Mouse interferons induced by ultraviolet-irradiated Newcastle disease virus were separated into three components by chromatography on CH-Sepharose 4B. Interferons produced by T and B lymphocytes consisted primarily of component 1 (unbound fraction), whereas interferons produced by macrophages or mouse embryo cells consisted primarily of component 3 (eluted by 0.5 M NaCl). Component 1 was heat stable and of low antigenicity against ALI, properties characteristic of T- and B-cell interferon. Components 2 and 3 were heat labile and of high antigenicity against ALI, properties characteristic of macrophage and mouse embryo cell interferon. In contrast, interferon induced in mice sensitized with  BCG differed from these interferons induced in B cells, T cells, macrophages, and fibroblasts in being extremely acid labile and nonreactive against ALI.", "contents": "Differences in mouse interferons according to cell source and mode of induction. Mouse interferon induced by ultraviolet-irradiated Newcastle disease virus or polyriboinosinic-polyribocytidylic acid in T lymphocytes, B lymphocytes, macrophages, and primary mouse embryonic cell culture was studied. Irrespective of the inducer, interferons produced by T or B lymphocytes were relatively heat stable and of low antigenicity when reacted with antiserum against L-cell interferon (ALI), whereas interferons produced by macrophages and mouse embryo cells were heat labile and of high antigenicity against ALI. Mouse interferons induced by ultraviolet-irradiated Newcastle disease virus were separated into three components by chromatography on CH-Sepharose 4B. Interferons produced by T and B lymphocytes consisted primarily of component 1 (unbound fraction), whereas interferons produced by macrophages or mouse embryo cells consisted primarily of component 3 (eluted by 0.5 M NaCl). Component 1 was heat stable and of low antigenicity against ALI, properties characteristic of T- and B-cell interferon. Components 2 and 3 were heat labile and of high antigenicity against ALI, properties characteristic of macrophage and mouse embryo cell interferon. In contrast, interferon induced in mice sensitized with  BCG differed from these interferons induced in B cells, T cells, macrophages, and fibroblasts in being extremely acid labile and nonreactive against ALI."}
{"id": "PMID:20404", "title": "Repression of heat-stable enterotoxin synthesis in enterotoxigenic Escherichia coli.", "content": "Five different carbon sources were examined for their ability to control synthesis of heat-stable enterotoxin (ST) by enterotoxigenic (ENT+) Escherichia coli grown in either a defined medium containing four amino acids or a minimal salts medium. No ST activity was observed when D-glucose, D-gluconate, and L-arabinose were added separately to the defined medium, whereas glycerol and pyruvate decreased toxin levels. Similar results were obtained using a minimal salts medium, except with pyruvate, which did not support growth. Inhibition of ST synthesis by D-glucose was overcome by the addition of 3 X 10(-3) M cyclic adenosine 3',5'-monophosphate. Glucose repression of beta-galactosidase synthesis under conditions optimal for inhibition of ST synthesis was also reversed by exogenous cyclic adenosine 3',5'-monophosphate in the presence of the inducer isopropyl-beta-D-thiogalactopyranoside. The data suggest that control mechanisms for the synthesis of plasmid gene products of bacterial pathogens are similar to those exerted on the host chromosome.", "contents": "Repression of heat-stable enterotoxin synthesis in enterotoxigenic Escherichia coli. Five different carbon sources were examined for their ability to control synthesis of heat-stable enterotoxin (ST) by enterotoxigenic (ENT+) Escherichia coli grown in either a defined medium containing four amino acids or a minimal salts medium. No ST activity was observed when D-glucose, D-gluconate, and L-arabinose were added separately to the defined medium, whereas glycerol and pyruvate decreased toxin levels. Similar results were obtained using a minimal salts medium, except with pyruvate, which did not support growth. Inhibition of ST synthesis by D-glucose was overcome by the addition of 3 X 10(-3) M cyclic adenosine 3',5'-monophosphate. Glucose repression of beta-galactosidase synthesis under conditions optimal for inhibition of ST synthesis was also reversed by exogenous cyclic adenosine 3',5'-monophosphate in the presence of the inducer isopropyl-beta-D-thiogalactopyranoside. The data suggest that control mechanisms for the synthesis of plasmid gene products of bacterial pathogens are similar to those exerted on the host chromosome."}
{"id": "PMID:20405", "title": "Complement levels in pneumococcal pneumonia.", "content": "Levels of complement proteins and functional activity of the alternate complement pathway were assessed in 39 patients with pneumococcal pneumonia. Mean levels of C3 and properdin and the functional activity of the alternate pathway in acute sera were significantly (P less than 0.05) below normal, whereas levels of components of the early classical pathway were normal. Although levels of factor B were in the normal range, they correlated significantly with C3 levels; there was no significant relation between C3 levels and C4 or C1q levels. The 19 patients iwth pneumococcal pneumonia and bacteremia had significantly lower mean values of properdin and factor B than the 20 patients without bacteremia, suggesting a more severe depression of the alternate complement pathway with bacteremia. During convalescence, complement levels were normal or elevated in most of the patients, but mean levels of properdin remained significantly below normal in bacteremic patients. Functional activity of the alternate pathway also remained below normal. These results indicate that there is a selective depression of the alternate pathway in patients with pneumococcal pneumonia, and they are consistent with the concept that the alternate pathway has an important role in host defenses in pneumococcal infection.", "contents": "Complement levels in pneumococcal pneumonia. Levels of complement proteins and functional activity of the alternate complement pathway were assessed in 39 patients with pneumococcal pneumonia. Mean levels of C3 and properdin and the functional activity of the alternate pathway in acute sera were significantly (P less than 0.05) below normal, whereas levels of components of the early classical pathway were normal. Although levels of factor B were in the normal range, they correlated significantly with C3 levels; there was no significant relation between C3 levels and C4 or C1q levels. The 19 patients iwth pneumococcal pneumonia and bacteremia had significantly lower mean values of properdin and factor B than the 20 patients without bacteremia, suggesting a more severe depression of the alternate complement pathway with bacteremia. During convalescence, complement levels were normal or elevated in most of the patients, but mean levels of properdin remained significantly below normal in bacteremic patients. Functional activity of the alternate pathway also remained below normal. These results indicate that there is a selective depression of the alternate pathway in patients with pneumococcal pneumonia, and they are consistent with the concept that the alternate pathway has an important role in host defenses in pneumococcal infection."}
{"id": "PMID:20406", "title": "Cell envelope of Neisseria gonorrhoeae: relationship between autolysis in buffer and the hydrolysis of peptidoglycan.", "content": "Neisseria gonorrhoeae readily underwent autolysis when suspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer at alkaline pH values. Autolysis was inhibited by the addition of Mg2+ or other divalent cations. Autolysis was also suppressed at acid pH (pH 6.0). Suspension of cells in buffer was accompanied by the hydrolysis of peptidoglycan. The rate of peptidoglycan hydrolysis in HEPES buffer was maximal at pH 8.5 and was similar in the presence or absence of Mg2+. Therefore, divalent cation stabilization against autolysis is not mediated by inhibition of peptidoglycan hydrolysis. Peptidoglycan hydrolysis occurred in HEPES buffer (pH 6.0), but at a rate that was 50% of the maximum. Incubation of cells with chloramphenicol or rifampin before suspension in HEPES buffer (pH 8.5) partially prevented autolysis; under these conditions, peptidoglycan hydrolysis still occurred, but at a reduced rate. Old and new peptidoglycans were hydrolyzed at similar rates. Peptidoglycan hydrolysis results in solubilization of both the peptide and glycan moieties.", "contents": "Cell envelope of Neisseria gonorrhoeae: relationship between autolysis in buffer and the hydrolysis of peptidoglycan. Neisseria gonorrhoeae readily underwent autolysis when suspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer at alkaline pH values. Autolysis was inhibited by the addition of Mg2+ or other divalent cations. Autolysis was also suppressed at acid pH (pH 6.0). Suspension of cells in buffer was accompanied by the hydrolysis of peptidoglycan. The rate of peptidoglycan hydrolysis in HEPES buffer was maximal at pH 8.5 and was similar in the presence or absence of Mg2+. Therefore, divalent cation stabilization against autolysis is not mediated by inhibition of peptidoglycan hydrolysis. Peptidoglycan hydrolysis occurred in HEPES buffer (pH 6.0), but at a rate that was 50% of the maximum. Incubation of cells with chloramphenicol or rifampin before suspension in HEPES buffer (pH 8.5) partially prevented autolysis; under these conditions, peptidoglycan hydrolysis still occurred, but at a reduced rate. Old and new peptidoglycans were hydrolyzed at similar rates. Peptidoglycan hydrolysis results in solubilization of both the peptide and glycan moieties."}
{"id": "PMID:20407", "title": "Delayed hypersensitivity in tumor-bearing mice. In vitro activation of \"eclipsed\" spleen cells.", "content": "At various stages during the progressive growth of a transplanted sarcoma in BALB/c mice, the delayed hypersensitivity response to tumor antigen was determined using the food-pad swelling test (FPS) and the leukocyte migration inhibition assay (LMI). A close correlation was observed between the in vivo and in vitro assays. \"Early\" recognition of tumor antigen was detected 24 h after tumor inoculation by both techniques and this positive response was maintained until day 15. As the tumor grew larger, the delayed hypersensitivity response in vivo vanished, while the delayed hypersensitivity response in vitro disappeared about 3 days later. This suppression or \"eclipse\" of the anti-tumor cellular immune response was specific for the type of tumor used, and could be reversed in vitro by means of a low pH treatment of lymphoid cells.", "contents": "Delayed hypersensitivity in tumor-bearing mice. In vitro activation of \"eclipsed\" spleen cells. At various stages during the progressive growth of a transplanted sarcoma in BALB/c mice, the delayed hypersensitivity response to tumor antigen was determined using the food-pad swelling test (FPS) and the leukocyte migration inhibition assay (LMI). A close correlation was observed between the in vivo and in vitro assays. \"Early\" recognition of tumor antigen was detected 24 h after tumor inoculation by both techniques and this positive response was maintained until day 15. As the tumor grew larger, the delayed hypersensitivity response in vivo vanished, while the delayed hypersensitivity response in vitro disappeared about 3 days later. This suppression or \"eclipse\" of the anti-tumor cellular immune response was specific for the type of tumor used, and could be reversed in vitro by means of a low pH treatment of lymphoid cells."}
{"id": "PMID:20409", "title": "Lack of association of the development of anti-sperm antibodies and other autoantibodies as a consequence of vasectomy.", "content": "The possibility of autoantibodies--other than sperm antibodies--developing as a consequence of vasectomy has been investigated in 255 volunteers. During the first year after vasectomy no obvious increase was observed in the occurrence of any of these antibodies (rheumatoid factor, antinuclear antibodies and antibodies against smooth muscle, mitochondria, gastric parietal cell, thyroid microsomes and thyroglobulin). Ninety-nine of the patients were also examined for agglutinating and immunofluorescent antibodies to sperm to see if there was any relationship between the occurrence of anti-sperm antibodies and other autoantibodies. However, the prevalence of non-sperm autoantibodies did not differ in two nearly equal groups of patients with and without indications of autoimmune reactions to spermatozoa, respectively. Consequently the present results lend no support to the hypothesis that vasectomy could induce autoimmunity to other autoantigens than sperm-specific antigens.", "contents": "Lack of association of the development of anti-sperm antibodies and other autoantibodies as a consequence of vasectomy. The possibility of autoantibodies--other than sperm antibodies--developing as a consequence of vasectomy has been investigated in 255 volunteers. During the first year after vasectomy no obvious increase was observed in the occurrence of any of these antibodies (rheumatoid factor, antinuclear antibodies and antibodies against smooth muscle, mitochondria, gastric parietal cell, thyroid microsomes and thyroglobulin). Ninety-nine of the patients were also examined for agglutinating and immunofluorescent antibodies to sperm to see if there was any relationship between the occurrence of anti-sperm antibodies and other autoantibodies. However, the prevalence of non-sperm autoantibodies did not differ in two nearly equal groups of patients with and without indications of autoimmune reactions to spermatozoa, respectively. Consequently the present results lend no support to the hypothesis that vasectomy could induce autoimmunity to other autoantigens than sperm-specific antigens."}
{"id": "PMID:20410", "title": "Mixed lymphocyte culture responses in infertile couples.", "content": "Twenty couples suffering from unexplained infertility have been tested in mixed leucocyte culture to determine if the wives were preimmunized against their husbands. The wives were tested against their husbands and four unrelated persons, and thymidine incorporation was measured on the third and fifth days of culture. No evidence was found that would indicate a preimmunization of the wife against her husband as an explanation for their infertility. A slight MLC stimulatory capacity was found in sera from infertile women.", "contents": "Mixed lymphocyte culture responses in infertile couples. Twenty couples suffering from unexplained infertility have been tested in mixed leucocyte culture to determine if the wives were preimmunized against their husbands. The wives were tested against their husbands and four unrelated persons, and thymidine incorporation was measured on the third and fifth days of culture. No evidence was found that would indicate a preimmunization of the wife against her husband as an explanation for their infertility. A slight MLC stimulatory capacity was found in sera from infertile women."}
{"id": "PMID:20411", "title": "A simplified determination of the urinary luteinizing hormone surge using the hemagglutination inhibition test.", "content": "The hemagglutination-inhibition test for urinary luteinizing hormone (LH) has been modified so that the test for LH surge can be assayed in 1 day. A first morning voided urine specimen submitted to the laboratory can be analyzed in 5 hours by ordinary bench procedures. This modification involves a 20-fold reduction, as compared with the older procedure, of the duration of incubation of the urine-antiserum mixture. Another modification is the choice of aliquots which are adaptable to automatic pipetting. Only a single dilution of urine is necessary to determine LH surge for the anticipation of ovulation. Daily LH determinations on 12 normally menstruating women (av. cycle 28.18 days) reveal consistent patterns. For the 40 cycles studied LH surge occurred 14.29 days (av.) prior to the onset of the next menstruation and coincided with the rise in basal body temperature. One woman with an unusually high incidence of familial twinning showed two large LH surges in each consecutive cycle.", "contents": "A simplified determination of the urinary luteinizing hormone surge using the hemagglutination inhibition test. The hemagglutination-inhibition test for urinary luteinizing hormone (LH) has been modified so that the test for LH surge can be assayed in 1 day. A first morning voided urine specimen submitted to the laboratory can be analyzed in 5 hours by ordinary bench procedures. This modification involves a 20-fold reduction, as compared with the older procedure, of the duration of incubation of the urine-antiserum mixture. Another modification is the choice of aliquots which are adaptable to automatic pipetting. Only a single dilution of urine is necessary to determine LH surge for the anticipation of ovulation. Daily LH determinations on 12 normally menstruating women (av. cycle 28.18 days) reveal consistent patterns. For the 40 cycles studied LH surge occurred 14.29 days (av.) prior to the onset of the next menstruation and coincided with the rise in basal body temperature. One woman with an unusually high incidence of familial twinning showed two large LH surges in each consecutive cycle."}
{"id": "PMID:20412", "title": "Hysteroscopic sterilization--a routine method?", "content": "Our intention was to sterilize 50 women by means of hysteroscopic sterilization, and we were unsuccessful in 60% of these cases. All these women ran the risk of another pregnancy with hysteroscopic sterilization alone. Therefore--in our opinion--the method of hysteroscopic sterilization by thermocoagulation of the intramural part of the tubes is not yet a routine method, at least not before another modification of this method or instruments makes it possible to obtain better results.", "contents": "Hysteroscopic sterilization--a routine method? Our intention was to sterilize 50 women by means of hysteroscopic sterilization, and we were unsuccessful in 60% of these cases. All these women ran the risk of another pregnancy with hysteroscopic sterilization alone. Therefore--in our opinion--the method of hysteroscopic sterilization by thermocoagulation of the intramural part of the tubes is not yet a routine method, at least not before another modification of this method or instruments makes it possible to obtain better results."}
{"id": "PMID:20408", "title": "Fatty acid synthesizing enzyme activity of cultured Mycobacterium lepraemurium.", "content": "In comparing the specific activity of enzymes pertaining to the biosynthesis of fatty acids in crude extracts of cultivated M. lepraemurium and M. smegmatis, it was found that: 1. The activity of acetyl CoA carboxylase of the former organism was undetectable and that of de novo fatty acid synthetase was too weak to measure exactly, under the condition used, whereas both activities of the latter organism were comparable to those already reported by other authors. 2. The activity of acetyl CoA dependent acyl CoA elongation system of M. lepraemurium was relatively high and close to that of M. smegmatis. 3. The activities of acetyl CoA synthetase and acyl CoA synthetase of M. lepraemurium were moderately lower than those of M. smegmatis. The relation between this peculiar fatty acid synthesizing enzyme system of M. lepraemurium and its extremely sluggish growth is discussed.", "contents": "Fatty acid synthesizing enzyme activity of cultured Mycobacterium lepraemurium. In comparing the specific activity of enzymes pertaining to the biosynthesis of fatty acids in crude extracts of cultivated M. lepraemurium and M. smegmatis, it was found that: 1. The activity of acetyl CoA carboxylase of the former organism was undetectable and that of de novo fatty acid synthetase was too weak to measure exactly, under the condition used, whereas both activities of the latter organism were comparable to those already reported by other authors. 2. The activity of acetyl CoA dependent acyl CoA elongation system of M. lepraemurium was relatively high and close to that of M. smegmatis. 3. The activities of acetyl CoA synthetase and acyl CoA synthetase of M. lepraemurium were moderately lower than those of M. smegmatis. The relation between this peculiar fatty acid synthesizing enzyme system of M. lepraemurium and its extremely sluggish growth is discussed."}
{"id": "PMID:20413", "title": "The selection of Y-chromatin positive spermatozoa and subsequent in vitro penetration through cervical mucus.", "content": "We carried out a check of Ericsson's data on the possibility of separating out Y-spermatozoa and their selective enrichement. Layers of spermatozoa were laid on BSA media of various concentrations, filtered and the Y-chromatin proportion was determined. The method used was that of fluorochromation with quinacrine mustard. Our selection experiments revealed a lower enrichment effect of Y-chromatin positive spermatozoa than that recorded by Ericsson et al. An average enrichment of 75% was obtained. Modifications carried out with other variants of the BSA gradient overlays achieved varying enrichment effects respectively. In order to check the subsequent progressive motility of the spermatozoa selected, we performed tests on in vitro penetration through cervical mucus, using the previously enriched Y-spermatozoa material. After the in vitro penetration test we were able to investigate the Y-chromatin proportion of a sufficient number of highly mobile spermatozoa after 60-mm penetration per hour. There was no significant change in the enrichment effect of the Y-spermatozoa during the in vitro penetration test.", "contents": "The selection of Y-chromatin positive spermatozoa and subsequent in vitro penetration through cervical mucus. We carried out a check of Ericsson's data on the possibility of separating out Y-spermatozoa and their selective enrichement. Layers of spermatozoa were laid on BSA media of various concentrations, filtered and the Y-chromatin proportion was determined. The method used was that of fluorochromation with quinacrine mustard. Our selection experiments revealed a lower enrichment effect of Y-chromatin positive spermatozoa than that recorded by Ericsson et al. An average enrichment of 75% was obtained. Modifications carried out with other variants of the BSA gradient overlays achieved varying enrichment effects respectively. In order to check the subsequent progressive motility of the spermatozoa selected, we performed tests on in vitro penetration through cervical mucus, using the previously enriched Y-spermatozoa material. After the in vitro penetration test we were able to investigate the Y-chromatin proportion of a sufficient number of highly mobile spermatozoa after 60-mm penetration per hour. There was no significant change in the enrichment effect of the Y-spermatozoa during the in vitro penetration test."}
{"id": "PMID:20414", "title": "Etiology, clinical features and prognosis in secondary amenorrhea.", "content": "A clinical investigation of 356 patients with secondary amenorrhea revealed that 95% of patients with postpill amenorrhea and 56% of patients with anorexia nervosa recovered in 6 years. The corresponding recovery rates for patients with psychogenic amenorrhea and amenorrhea following self-induced weight loss were 72% for both groups, and in patients with the amenorrhea-galactorrhea syndrome and idiophatic functional amenorrhea the recovery rates at 6 years were 64 and 61% respectively. Unlike the other groups with functional amenorrhea, patients with the amenorrhea-galactorrhea syndrome had impaired ovarian responsiveness to exogenous gonadotropins. Bromocriptine treatment resulted in disappearance of the galactorrhea and restoration of the menses and/or ovulation in nine of 18 patients; of these three became pregnant. The effect of bromocriptine did not persist for long after treatment ceased, and permanent recovery was recorded only in four patients. The group with functional amenorrhea included 34 patients who wished to become pregnant. Gonadotropin treatment was successful in 20 patients, clomiphene-hCG in two, tamoxifen in two, bromocriptine in two, and combined bromocriptine and clomiphene in one. Thus, the overall pregnancy rate in patients with functional amenorrhea was 79%. The groups with ovarian amenorrhea inclutients with assumed ovarian failure responded to large doses of exogenous gonadotropins by ovulation and three became pregnant. Ovarian wedge resection was ineffective in all five cases with polycystic ovaries, but two patients became pregnant after treatment with clomiphene and chorionic gonadotropin, and one with exogenous gonadotropins.", "contents": "Etiology, clinical features and prognosis in secondary amenorrhea. A clinical investigation of 356 patients with secondary amenorrhea revealed that 95% of patients with postpill amenorrhea and 56% of patients with anorexia nervosa recovered in 6 years. The corresponding recovery rates for patients with psychogenic amenorrhea and amenorrhea following self-induced weight loss were 72% for both groups, and in patients with the amenorrhea-galactorrhea syndrome and idiophatic functional amenorrhea the recovery rates at 6 years were 64 and 61% respectively. Unlike the other groups with functional amenorrhea, patients with the amenorrhea-galactorrhea syndrome had impaired ovarian responsiveness to exogenous gonadotropins. Bromocriptine treatment resulted in disappearance of the galactorrhea and restoration of the menses and/or ovulation in nine of 18 patients; of these three became pregnant. The effect of bromocriptine did not persist for long after treatment ceased, and permanent recovery was recorded only in four patients. The group with functional amenorrhea included 34 patients who wished to become pregnant. Gonadotropin treatment was successful in 20 patients, clomiphene-hCG in two, tamoxifen in two, bromocriptine in two, and combined bromocriptine and clomiphene in one. Thus, the overall pregnancy rate in patients with functional amenorrhea was 79%. The groups with ovarian amenorrhea inclutients with assumed ovarian failure responded to large doses of exogenous gonadotropins by ovulation and three became pregnant. Ovarian wedge resection was ineffective in all five cases with polycystic ovaries, but two patients became pregnant after treatment with clomiphene and chorionic gonadotropin, and one with exogenous gonadotropins."}
{"id": "PMID:20415", "title": "Serum LH, FSH and testosterone response to the administration of a new LH-RH analog, D-Trp6-LH-RH, in normal men.", "content": "A long-acting superactive analog of LH-RH, D-Trp6-LH-RH was given to 23 normal men by several routes of administration (iv, im, sc, continuous infusion) and in increasing doses of 1 to 50 microgram. LH and FSH responses were obtained at doses as low as 2.5 microgram. The maximal absolute LH and FSH increment in response to a 10 microgram iv bolus injection of this analog was similar to 100 microgram of LH-RH. In addition, after administration of the analog the LH and FSH level was maintained at a higher than basal level for at least 8 hours. With a 50 microgram iv bolus injection, from 30 minutes onwards the increases in LH levels were significantly greater (P less than 0.05) than those elicited by the 10 microgram dose for at least 8 hours. Maximum release of LH and RSH was observed when this same dose was given as continuous infusion for 8 hours (P less than 0.05). There seemed to be no significant differences between the im and sc routes. Following the administration of the D-Trp6-LH-RH, testosterone levels were maintained above the normal values (P less than 0.02). The high potency and prolonged duration of action of this compound suggest its potential usefulness for increasing testosterone levels and for stimulation of spermatogenesis in men.", "contents": "Serum LH, FSH and testosterone response to the administration of a new LH-RH analog, D-Trp6-LH-RH, in normal men. A long-acting superactive analog of LH-RH, D-Trp6-LH-RH was given to 23 normal men by several routes of administration (iv, im, sc, continuous infusion) and in increasing doses of 1 to 50 microgram. LH and FSH responses were obtained at doses as low as 2.5 microgram. The maximal absolute LH and FSH increment in response to a 10 microgram iv bolus injection of this analog was similar to 100 microgram of LH-RH. In addition, after administration of the analog the LH and FSH level was maintained at a higher than basal level for at least 8 hours. With a 50 microgram iv bolus injection, from 30 minutes onwards the increases in LH levels were significantly greater (P less than 0.05) than those elicited by the 10 microgram dose for at least 8 hours. Maximum release of LH and RSH was observed when this same dose was given as continuous infusion for 8 hours (P less than 0.05). There seemed to be no significant differences between the im and sc routes. Following the administration of the D-Trp6-LH-RH, testosterone levels were maintained above the normal values (P less than 0.02). The high potency and prolonged duration of action of this compound suggest its potential usefulness for increasing testosterone levels and for stimulation of spermatogenesis in men."}
{"id": "PMID:20416", "title": "In vitro stimulation of human sperm motility by acetylcarnitine.", "content": "An increase in motility of ejaculated human spermatozoa was observed after the addition of acetylcaritine or carnitine. Similar results were also obtained in the diluted semen with 25--30% initial motilities. However, indirect evidence suggests that carnitine is converted to acetylcarnitine prior to its stimulatory action. In addition, this stimulation was shown to be the result of no increase in ionic strength nor any change in the levels of ATP.", "contents": "In vitro stimulation of human sperm motility by acetylcarnitine. An increase in motility of ejaculated human spermatozoa was observed after the addition of acetylcaritine or carnitine. Similar results were also obtained in the diluted semen with 25--30% initial motilities. However, indirect evidence suggests that carnitine is converted to acetylcarnitine prior to its stimulatory action. In addition, this stimulation was shown to be the result of no increase in ionic strength nor any change in the levels of ATP."}
{"id": "PMID:20417", "title": "Osmolality and conductance of normal and abnormal human seminal plasma.", "content": "The possible correlation between two important general properties of seminal plasma, osmolality and conductance, and the presence of some pathological conditions of human semen, asthenospermia and oligoasthenospermia, have been studied. Osmolality was measured under carefully controlled conditions by the freezing point depression method and conductance with  a Wheatstone bridge. In addition, volume, by an isotopic dilution method, and pH were also determined. Osmolality of normal human seminal plasma (366 +/- 16 mOsm/Kg) was found to be higher than the osmolality of human blood serum. Abnormal seminal plasma showed a still higher value (428 +/- 38 and 457 +/- 49 mOsm/Kg respectively for astheno- and oligoasthenospermic subjects). Incubation of normal seminal plasma for 24 hours at room temperature produced a significant increase in osmolality (from 366 +/- 16 to 430 +/- 31 mOsm/Kg) while pathological seminal plasma failed to show any modification. Osmolality and conductance values were found to be correlated with semen ejaculated volume in normal subjects. No difference in mean conductance value was found between normal and asthenospermic individuals (10.4 +/- 1.2 against 9.9 +/- 1.0 mhos X 10(-3) respectively). Oligoasthenospermics showed, on the contrary, a significantly higher conductance (12.4 +/- 1.6 mhos X 10(-3)).", "contents": "Osmolality and conductance of normal and abnormal human seminal plasma. The possible correlation between two important general properties of seminal plasma, osmolality and conductance, and the presence of some pathological conditions of human semen, asthenospermia and oligoasthenospermia, have been studied. Osmolality was measured under carefully controlled conditions by the freezing point depression method and conductance with  a Wheatstone bridge. In addition, volume, by an isotopic dilution method, and pH were also determined. Osmolality of normal human seminal plasma (366 +/- 16 mOsm/Kg) was found to be higher than the osmolality of human blood serum. Abnormal seminal plasma showed a still higher value (428 +/- 38 and 457 +/- 49 mOsm/Kg respectively for astheno- and oligoasthenospermic subjects). Incubation of normal seminal plasma for 24 hours at room temperature produced a significant increase in osmolality (from 366 +/- 16 to 430 +/- 31 mOsm/Kg) while pathological seminal plasma failed to show any modification. Osmolality and conductance values were found to be correlated with semen ejaculated volume in normal subjects. No difference in mean conductance value was found between normal and asthenospermic individuals (10.4 +/- 1.2 against 9.9 +/- 1.0 mhos X 10(-3) respectively). Oligoasthenospermics showed, on the contrary, a significantly higher conductance (12.4 +/- 1.6 mhos X 10(-3))."}
{"id": "PMID:20418", "title": "Uterine synechiae: variations in severity and some conditions which may be conducive to severe adhesions.", "content": "Considerable variability in the severity of Asherman's syndrome was observed, and a high incidence of other gynecological disorders was discovered, mainly by endoscopy, in patients with intrauterine synechiae. Fifty-seven cases were reviewed in an attempt (1) to discover factors contributing to severity, (2) to examine possible relationships between other pelvic pathologies and the development of synechiae, and, subsequently, (3) to revise methods of treatment. Thirty-nine women underwent some form of pelvic visualization; twenty-seven (69%) were found to have other gynecological disorders. Forty-six patients had had a recent D & C. Signs of pituitary hypogonadotropism appeared in five of the 17 women with severe adhesions, suggesting that severity of adhesions developed after D & C may be increased in the presence of a concurrently existing hypoestrogenic state.", "contents": "Uterine synechiae: variations in severity and some conditions which may be conducive to severe adhesions. Considerable variability in the severity of Asherman's syndrome was observed, and a high incidence of other gynecological disorders was discovered, mainly by endoscopy, in patients with intrauterine synechiae. Fifty-seven cases were reviewed in an attempt (1) to discover factors contributing to severity, (2) to examine possible relationships between other pelvic pathologies and the development of synechiae, and, subsequently, (3) to revise methods of treatment. Thirty-nine women underwent some form of pelvic visualization; twenty-seven (69%) were found to have other gynecological disorders. Forty-six patients had had a recent D & C. Signs of pituitary hypogonadotropism appeared in five of the 17 women with severe adhesions, suggesting that severity of adhesions developed after D & C may be increased in the presence of a concurrently existing hypoestrogenic state."}
{"id": "PMID:20424", "title": "Urinary excretion of uricine.", "content": "The excretion of uricine or yellowish-red pigment from uric acid stones and its binding by uric acid seems to affect the precipitation of uric acid. Uricine was determined by ion exchange chromatography followed by measurement of the alkaline fluorescence emission. The uricine urinary excretion and the uricine-uric acid potential binding were determined in 11 control subjects, 20 recurrent uric acid stone formers, seven calcium stone formers with hyperuricuria, and five gouty patients without urinary stone formation. Uricine excretion was increased in 11 uric acid stone formers, whereas it was normal in the rest of the patients. Uricine-uric acid potential binding was increased in many uric acid stone formers, despite the absence of uric acid urinary hyperexcretion, whereas it was normal in most of the calcium stone formers and was moderately increased in the gouty patients.", "contents": "Urinary excretion of uricine. The excretion of uricine or yellowish-red pigment from uric acid stones and its binding by uric acid seems to affect the precipitation of uric acid. Uricine was determined by ion exchange chromatography followed by measurement of the alkaline fluorescence emission. The uricine urinary excretion and the uricine-uric acid potential binding were determined in 11 control subjects, 20 recurrent uric acid stone formers, seven calcium stone formers with hyperuricuria, and five gouty patients without urinary stone formation. Uricine excretion was increased in 11 uric acid stone formers, whereas it was normal in the rest of the patients. Uricine-uric acid potential binding was increased in many uric acid stone formers, despite the absence of uric acid urinary hyperexcretion, whereas it was normal in most of the calcium stone formers and was moderately increased in the gouty patients."}
{"id": "PMID:20427", "title": "Localization of histamine and histamine H2-receptor antagonists in the gastric mucosa.", "content": "Histamine stimulates acid secretion by the parietal cell and this secretion is inhibited by the histamine H2-receptor antagonists. Whole body autoradiography showed that radioactivity from 14C-histamine was localized in the artery walls of the stomach and in the muscularis mucosae, but that the level in the fundic mucosa was the same as the blood. When the H2-receptor antagonists burimamide, metiamide and cimetidine were labelled with 35S, 14C or 3H and dosed to rats, whole body autoradiography showed that the stomach was predominantly labelled in the glandular mucosa from 5 to 120 min after administration. Microautoradiography in the rat and dog after intravenous injection of [3H]metiamide or [3H]cimetidine demonstrated an uptake of tritium in the parietal cell cytoplasm that was 3- to 4-times greater than that found in adjacent peptic cells or areas of muscularis mucosa. The preferential labelling persisted at a low level up to 6h after injection in the rat. The localization of radioactivity from the H2-antagonists in the parietal cell cytoplasm correlates well with their pharmacological activity in preventing acid secretion from this cell.", "contents": "Localization of histamine and histamine H2-receptor antagonists in the gastric mucosa. Histamine stimulates acid secretion by the parietal cell and this secretion is inhibited by the histamine H2-receptor antagonists. Whole body autoradiography showed that radioactivity from 14C-histamine was localized in the artery walls of the stomach and in the muscularis mucosae, but that the level in the fundic mucosa was the same as the blood. When the H2-receptor antagonists burimamide, metiamide and cimetidine were labelled with 35S, 14C or 3H and dosed to rats, whole body autoradiography showed that the stomach was predominantly labelled in the glandular mucosa from 5 to 120 min after administration. Microautoradiography in the rat and dog after intravenous injection of [3H]metiamide or [3H]cimetidine demonstrated an uptake of tritium in the parietal cell cytoplasm that was 3- to 4-times greater than that found in adjacent peptic cells or areas of muscularis mucosa. The preferential labelling persisted at a low level up to 6h after injection in the rat. The localization of radioactivity from the H2-antagonists in the parietal cell cytoplasm correlates well with their pharmacological activity in preventing acid secretion from this cell."}
{"id": "PMID:20432", "title": "Professional nursing in the Soviet Union.", "content": "Professional nurses in the Soviet Union are trained by physicians. Their professional training is planned to produce efficient, middle level, clinical workers. At all times nurses work under physician supervision. The Soviet nurse works in clinical facilities and with equipment that appears old-fashioned by American standards but they provide the highest quality of nursing care.", "contents": "Professional nursing in the Soviet Union. Professional nurses in the Soviet Union are trained by physicians. Their professional training is planned to produce efficient, middle level, clinical workers. At all times nurses work under physician supervision. The Soviet nurse works in clinical facilities and with equipment that appears old-fashioned by American standards but they provide the highest quality of nursing care."}
{"id": "PMID:20436", "title": "Bacterial metabolism of anthracycline antibiotics. Steffimycinone and steffimycinol conversions.", "content": "Streptomyces nogalater, UC-2783, and Streptomyces peucetius var. caesius, IMRU-3920/UC-5633, catalyze ketonic carbonyl reduction of steffimycinone (1, Scheme 1). Using cell-free preparations of S. nogalater, the process of ketonic carbonyl reduction has been shown to be TPNH linked. The product, steffimycinol (2), is reduced further by Aeromonas hydrophila, 2C/UC-6303, by the process of microaerophilic conversion of anthracyclinones previously reported1,2) with the result being the formation of 7-deoxysteffimycinol (3). The products (2 and 3) were isolated by extraction from the fermentations followed by chromatographic purification. Identification was by comparison of various physical properties and spectral data with those of authentic materials obtained by chemical means. Catalytic activity of the crude enzyme preparations of S. nogalater was lost by dialysis by restored by addition of TPNH although not by addition of DPNH demonstrating TPNH dependence. The reaction rate increased linearly with added crude enzyme protein up to 4 mg/ml and was highest between pH 6.5 and 7.0.", "contents": "Bacterial metabolism of anthracycline antibiotics. Steffimycinone and steffimycinol conversions. Streptomyces nogalater, UC-2783, and Streptomyces peucetius var. caesius, IMRU-3920/UC-5633, catalyze ketonic carbonyl reduction of steffimycinone (1, Scheme 1). Using cell-free preparations of S. nogalater, the process of ketonic carbonyl reduction has been shown to be TPNH linked. The product, steffimycinol (2), is reduced further by Aeromonas hydrophila, 2C/UC-6303, by the process of microaerophilic conversion of anthracyclinones previously reported1,2) with the result being the formation of 7-deoxysteffimycinol (3). The products (2 and 3) were isolated by extraction from the fermentations followed by chromatographic purification. Identification was by comparison of various physical properties and spectral data with those of authentic materials obtained by chemical means. Catalytic activity of the crude enzyme preparations of S. nogalater was lost by dialysis by restored by addition of TPNH although not by addition of DPNH demonstrating TPNH dependence. The reaction rate increased linearly with added crude enzyme protein up to 4 mg/ml and was highest between pH 6.5 and 7.0."}
{"id": "PMID:20440", "title": "Postcapillary changes in blood pH in vivo during carbonic anhydrase inhibition.", "content": "A rapidly responding stopped-flow glass pH electrode apparatus was used to investigate pH changes in blood in vivo after it exits from an exchange capillary. Arterial blood was drawn from anesthetized animals through the apparatus. Temperature and pH of the blood in the electrode chamber were continuously recorded, both during withdrawal and after flow was stopped. Blood pH did not change after stopping flow in control experiments. When benzolamide (2 mg/kg) was given to inhibit carbonic anhydrase activity available to plasma (e.g., due to lysis) while having less effect on intracellular activity, pH increased 0.02-0.04 (t1/2 approximately 8 s) after stopping flow. Administration of acetazolamide (50 mg/kg) resulted in pH decreasing 0.07-0.10 (t1/2 approximately 15 s) after stopping flow. Ventilation for 1 min with N2 resulted in an increased rise in pH for the benzolamide-treated animals but a decreased fall in pH for the acetazolamide-treated animals. These shifts in arterial blood pH after gas exchange are largely due to disequilibrium of [H+] between red cells and plasma at the end of the pulmonary capillary.", "contents": "Postcapillary changes in blood pH in vivo during carbonic anhydrase inhibition. A rapidly responding stopped-flow glass pH electrode apparatus was used to investigate pH changes in blood in vivo after it exits from an exchange capillary. Arterial blood was drawn from anesthetized animals through the apparatus. Temperature and pH of the blood in the electrode chamber were continuously recorded, both during withdrawal and after flow was stopped. Blood pH did not change after stopping flow in control experiments. When benzolamide (2 mg/kg) was given to inhibit carbonic anhydrase activity available to plasma (e.g., due to lysis) while having less effect on intracellular activity, pH increased 0.02-0.04 (t1/2 approximately 8 s) after stopping flow. Administration of acetazolamide (50 mg/kg) resulted in pH decreasing 0.07-0.10 (t1/2 approximately 15 s) after stopping flow. Ventilation for 1 min with N2 resulted in an increased rise in pH for the benzolamide-treated animals but a decreased fall in pH for the acetazolamide-treated animals. These shifts in arterial blood pH after gas exchange are largely due to disequilibrium of [H+] between red cells and plasma at the end of the pulmonary capillary."}
{"id": "PMID:20441", "title": "Cerebral glucose-6-phosphatase and the movement of 2-deoxy-D-glucose across cell membranes.", "content": "Glucose-6-phosphatase (glucose-6-phosphohydrolase and its associated phosphotransferase activities) was determined in brain tissue and in several preparations derived from brain tissue. These included purified capillaries and established cell lines of neuronal or glial origin. Since it has been suggested that glucose-6-phosphatase may be involved in sugar transport, the characteristics of that process were examined in these preparations. The pattern of uptake of 2-deoxy-D-glucose in four cell lines was shown to involve transport of the analog across the cell membrane that was more rapid than the subsequent phosphorylation of the sugar in the intracellular compartment. In the remaining cell lines and in purified capillaries, phosphorylation of 2-deoxy-D-glucose was at least as rapid as uptake. No differences could be found between the cells in these two categories with respect to amount or localization of glucose-6-phosphatase, ability to phosphorylate 3-O-methyl-D-glucose, or ability to phosphorylate extracellular and intracellular 2-deoxy-D-glucose. In the course of these experiments, it was found that there was a rapid efflux of 2-deoxy-D-glucose from cells that had taken up this sugar. The efflux involves a dephosphorylation step catalyzed by intracellular phosphatase that releases free sugar in the cytoplasm. Glucose-6-phosphatase thus probably has no major role in the phosphorylation of glucose in brain cells, but acts in the more conventional sense, i.e. as a phosphohydrolase.", "contents": "Cerebral glucose-6-phosphatase and the movement of 2-deoxy-D-glucose across cell membranes. Glucose-6-phosphatase (glucose-6-phosphohydrolase and its associated phosphotransferase activities) was determined in brain tissue and in several preparations derived from brain tissue. These included purified capillaries and established cell lines of neuronal or glial origin. Since it has been suggested that glucose-6-phosphatase may be involved in sugar transport, the characteristics of that process were examined in these preparations. The pattern of uptake of 2-deoxy-D-glucose in four cell lines was shown to involve transport of the analog across the cell membrane that was more rapid than the subsequent phosphorylation of the sugar in the intracellular compartment. In the remaining cell lines and in purified capillaries, phosphorylation of 2-deoxy-D-glucose was at least as rapid as uptake. No differences could be found between the cells in these two categories with respect to amount or localization of glucose-6-phosphatase, ability to phosphorylate 3-O-methyl-D-glucose, or ability to phosphorylate extracellular and intracellular 2-deoxy-D-glucose. In the course of these experiments, it was found that there was a rapid efflux of 2-deoxy-D-glucose from cells that had taken up this sugar. The efflux involves a dephosphorylation step catalyzed by intracellular phosphatase that releases free sugar in the cytoplasm. Glucose-6-phosphatase thus probably has no major role in the phosphorylation of glucose in brain cells, but acts in the more conventional sense, i.e. as a phosphohydrolase."}
{"id": "PMID:20445", "title": "Mast cell binding of neurotensin. I. Iodination of neurotensin and characterization of the interaction of neurotensin with mast cell receptor sites.", "content": "Neurotensin was iodinated at equimolar concentrations of peptide, iodide, and chloramine-T, producing a labeled peptide with a specific activity of 1000 to 2000 Ci/mmol. Rat mast cells specifically and reversibly bound 1.27 pmol of neurotensin/10(6) cells with a reversible affinity, KD, of 154 nM. Optimum specific binding occurred betwen pH 6.8 and 7.2 under hypotonic conditions and dropped sharply as buffer concentration increased beyond 10 mM. The divalent cations Ca2+ and Mg2+ prevented binding with 50% inhibition at 1.5 and 4 mM, respectively. Binding was strongly and equally inhibited by the sodium and potassium salts of chloride, bromide, and iodide, and to a lesser degree by LiCl. Maximum binding of 125I-neurotensin occurred within 10 min at 0 degrees, and within 1.5 to 2 min binding was reduced to half-maximum in the presence of excess unlabeled neurotensin or upon 20-fold dilution in buffer. Both CaCl2 and NaCl were able to dissociate 60% of the total bound neurotensin: half the label bound was removed in 4 to 6 min. EDTA inhibited the binding only at high concentrations and no requirement was found for sulfhydryl groups, ATP, or a glycoprotein in the binding of neurotensin.", "contents": "Mast cell binding of neurotensin. I. Iodination of neurotensin and characterization of the interaction of neurotensin with mast cell receptor sites. Neurotensin was iodinated at equimolar concentrations of peptide, iodide, and chloramine-T, producing a labeled peptide with a specific activity of 1000 to 2000 Ci/mmol. Rat mast cells specifically and reversibly bound 1.27 pmol of neurotensin/10(6) cells with a reversible affinity, KD, of 154 nM. Optimum specific binding occurred betwen pH 6.8 and 7.2 under hypotonic conditions and dropped sharply as buffer concentration increased beyond 10 mM. The divalent cations Ca2+ and Mg2+ prevented binding with 50% inhibition at 1.5 and 4 mM, respectively. Binding was strongly and equally inhibited by the sodium and potassium salts of chloride, bromide, and iodide, and to a lesser degree by LiCl. Maximum binding of 125I-neurotensin occurred within 10 min at 0 degrees, and within 1.5 to 2 min binding was reduced to half-maximum in the presence of excess unlabeled neurotensin or upon 20-fold dilution in buffer. Both CaCl2 and NaCl were able to dissociate 60% of the total bound neurotensin: half the label bound was removed in 4 to 6 min. EDTA inhibited the binding only at high concentrations and no requirement was found for sulfhydryl groups, ATP, or a glycoprotein in the binding of neurotensin."}
{"id": "PMID:20446", "title": "RNA polymerase activity in bovine spermatozoa.", "content": "Washed mature spermatozoa from bulls incorporate ribonucleoside triphosphates into RNA using an endogenous template. Maximum incorporation was observed at 31 degrees C in the presence of MgCl2, all four ribonucleoside triphosphates, beta-mercaptoethanol, and glycine sodium hydroxide buffer at pH 9.0. The amount of synthesis was linearly dependent upon the concentration of spermatozoa and continued for at least 4 h. Digestion studies revealed the RNA to be present in a protected (intracellular?) location in the spermatozoa. The RNA synthesis was inhibited by ethidium bromide, rifampicin, acriflavine, actinomycin D, and caffeine, but not by alpha-amanitine or rifamycin SV. Fractionation of the spermatozoa by sonication and separation of the heads and tails by centrifugation through a discontinuous gradient revealed that more than half of the total RNA polymerase activity was associated with the tail fraction.", "contents": "RNA polymerase activity in bovine spermatozoa. Washed mature spermatozoa from bulls incorporate ribonucleoside triphosphates into RNA using an endogenous template. Maximum incorporation was observed at 31 degrees C in the presence of MgCl2, all four ribonucleoside triphosphates, beta-mercaptoethanol, and glycine sodium hydroxide buffer at pH 9.0. The amount of synthesis was linearly dependent upon the concentration of spermatozoa and continued for at least 4 h. Digestion studies revealed the RNA to be present in a protected (intracellular?) location in the spermatozoa. The RNA synthesis was inhibited by ethidium bromide, rifampicin, acriflavine, actinomycin D, and caffeine, but not by alpha-amanitine or rifamycin SV. Fractionation of the spermatozoa by sonication and separation of the heads and tails by centrifugation through a discontinuous gradient revealed that more than half of the total RNA polymerase activity was associated with the tail fraction."}
{"id": "PMID:20447", "title": "The contractile basis of amoeboid movement. V. The control of gelation, solation, and contraction in extracts from Dictyostelium discoideum.", "content": "Motile extracts have been prepared from Dictyostelium discoideum by homogenization and differential centrifugation at 4 degrees C in a stabilization solution (60). These extracts gelled on warming to 25 degrees Celsius and contracted in response to micromolar Ca++ or a pH in excess of 7.0. Optimal gelation occurred in a solution containing 2.5 mM ethylene glycol-bis (beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA), 2.5 mM piperazine-N-N'-bis [2-ethane sulfonic acid] (PIPES), 1 mM MgC1(2), 1 mM ATP, and 20 mM KCI at ph 7.0 (relaxation solution), while micromolar levels of Ca++ inhibited gelation. Conditions that solated the gel elicited contraction of extracts containing myosin. This was true regardless of whether chemical (micromolar Ca++, pH >7.0, cytochalasin B, elevated concentrations of KCI, MgC1(2), and sucrose) or physical (pressure, mechanical stress, and cold) means were used to induce solation. Myosin was definitely required for contraction. During Ca++-or pH-elicited contraction: (a) actin, myosin, and a 95,000-dalton polypeptide were concentrated in the contracted extract; (b) the gelation activity was recovered in the material sqeezed out the contracting extract;(c) electron microscopy demonstrated that the number of free, recognizable F-actin filaments increased; (d) the actomyosin MgATPase activity was stimulated by 4- to 10-fold. In the absense of myosin the Dictyostelium extract did not contract, while gelation proceeded normally. During solation of the gel in the absense of myosin: (a) electron microscopy demonstrated that the number of free, recognizable F- actin filaments increased; (b) solation-dependent contraction of the extract and the Ca++-stimulated MgATPase activity were reconstituted by adding puried Dictyostelium myosin. Actin purified from the Dictyostelium extract did not gel (at 2 mg/ml), while low concentrations of actin (0.7-2 mg/ml) that contained several contaminating components underwent rapid Ca++ regulated gelation. These results indicated : (a) gelation in Dictyostelium extracts involves a specific Ca++-sensitive interaction between actin and several other components; (b) myosin is an absolute requirement for contraction of the extract; (c) actin-myosin interactions capable of producing force for movement are prevented in the gel, while solation of the gel by either physical or chemical means results in the release of F-actin capable of interaction with myosin and subsequent contraction. The effectiveness of physical agents in producting contraction suggests that the regulation of contraction by the gel is structural in nature.", "contents": "The contractile basis of amoeboid movement. V. The control of gelation, solation, and contraction in extracts from Dictyostelium discoideum. Motile extracts have been prepared from Dictyostelium discoideum by homogenization and differential centrifugation at 4 degrees C in a stabilization solution (60). These extracts gelled on warming to 25 degrees Celsius and contracted in response to micromolar Ca++ or a pH in excess of 7.0. Optimal gelation occurred in a solution containing 2.5 mM ethylene glycol-bis (beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA), 2.5 mM piperazine-N-N'-bis [2-ethane sulfonic acid] (PIPES), 1 mM MgC1(2), 1 mM ATP, and 20 mM KCI at ph 7.0 (relaxation solution), while micromolar levels of Ca++ inhibited gelation. Conditions that solated the gel elicited contraction of extracts containing myosin. This was true regardless of whether chemical (micromolar Ca++, pH >7.0, cytochalasin B, elevated concentrations of KCI, MgC1(2), and sucrose) or physical (pressure, mechanical stress, and cold) means were used to induce solation. Myosin was definitely required for contraction. During Ca++-or pH-elicited contraction: (a) actin, myosin, and a 95,000-dalton polypeptide were concentrated in the contracted extract; (b) the gelation activity was recovered in the material sqeezed out the contracting extract;(c) electron microscopy demonstrated that the number of free, recognizable F-actin filaments increased; (d) the actomyosin MgATPase activity was stimulated by 4- to 10-fold. In the absense of myosin the Dictyostelium extract did not contract, while gelation proceeded normally. During solation of the gel in the absense of myosin: (a) electron microscopy demonstrated that the number of free, recognizable F- actin filaments increased; (b) solation-dependent contraction of the extract and the Ca++-stimulated MgATPase activity were reconstituted by adding puried Dictyostelium myosin. Actin purified from the Dictyostelium extract did not gel (at 2 mg/ml), while low concentrations of actin (0.7-2 mg/ml) that contained several contaminating components underwent rapid Ca++ regulated gelation. These results indicated : (a) gelation in Dictyostelium extracts involves a specific Ca++-sensitive interaction between actin and several other components; (b) myosin is an absolute requirement for contraction of the extract; (c) actin-myosin interactions capable of producing force for movement are prevented in the gel, while solation of the gel by either physical or chemical means results in the release of F-actin capable of interaction with myosin and subsequent contraction. The effectiveness of physical agents in producting contraction suggests that the regulation of contraction by the gel is structural in nature."}
{"id": "PMID:20448", "title": "The stability of tyrosine aminotransferase and other proteins in enucleated rat hepatoma tissue culture cells.", "content": "The role of the nucleus in bringing about the induction of tyrosine aminotransferase (TAT) by glucocorticosteroid hormone and its deinduction upon steroid removal has been studied in enucleated rat hepatoma tissue culture cells (FU5-5). Both processes require the presence of the nucleus. However, cytoplasts from preinduced cells show an initial rapid decline in enzyme activity immediately after enucleation followed by maintenance of a constant level of activity. This initial decline in enzyme activity can be partially prevented by trypan blue, an inhibitor of lysosomal activity. This suggests that the early fall in enzyme activity could be due to an increase in the level of lysosomal activity immediately after enucleation. The subsequent constant level of activity seems due to maintenance rather than synthesis and degradation since it is not affected by cycloheximide. The absence of degradation applies to other kinds of proteins in enucleated FU5-5 cells and enucleated mouse fibroblast L cells. These experiments suggest that some kind of labile RNA or protein dependent on the presence of the nucleus is required for the degradation of all classes of proteins in different kinds of cells.", "contents": "The stability of tyrosine aminotransferase and other proteins in enucleated rat hepatoma tissue culture cells. The role of the nucleus in bringing about the induction of tyrosine aminotransferase (TAT) by glucocorticosteroid hormone and its deinduction upon steroid removal has been studied in enucleated rat hepatoma tissue culture cells (FU5-5). Both processes require the presence of the nucleus. However, cytoplasts from preinduced cells show an initial rapid decline in enzyme activity immediately after enucleation followed by maintenance of a constant level of activity. This initial decline in enzyme activity can be partially prevented by trypan blue, an inhibitor of lysosomal activity. This suggests that the early fall in enzyme activity could be due to an increase in the level of lysosomal activity immediately after enucleation. The subsequent constant level of activity seems due to maintenance rather than synthesis and degradation since it is not affected by cycloheximide. The absence of degradation applies to other kinds of proteins in enucleated FU5-5 cells and enucleated mouse fibroblast L cells. These experiments suggest that some kind of labile RNA or protein dependent on the presence of the nucleus is required for the degradation of all classes of proteins in different kinds of cells."}
{"id": "PMID:20450", "title": "Initiation of human parturition. VI. Identification and quantification of progesterone metabolites produced by the components of human fetal membranes.", "content": "The fetal membranes play a central role in the initiation of human parturition, a role that may be subserved in part by quantitative changes in progesterone metabolism. In order to identify and to quantify the metabolites of progesterone produced by the components of the human fetal membranes, amnion and chorion laeve tissues and homogenates were incubated with [3H]progesterone in the presence of added NADPH. The radioactive metabolites, 20alpha-hydroxy-4-pregnen-3-one, 5alpha-pregnane-3,20-dione and 3beta-hydroxy-5alpha-pregnan-20-one, were isolated and identified by derivative formation, a combination of chromatographic techniques, and by crystallization to constant specific activity after addition of authentic standards. A simplified technique of metabolite quantification was developed that involves one thin layer chromatographic procedure and liquid scintillation assay of radioactivity. The accuracy of this method was established by comparison with data obtained using classical techniques. This study demonstrates the presence of human fetal membranes 5alpha-reductase, 20alpha-hydroxysteroid oxidoreductase, and 3beta-hydroxy-steroid oxidoreductase, and a qualitative difference between amnion and chorion laeve.", "contents": "Initiation of human parturition. VI. Identification and quantification of progesterone metabolites produced by the components of human fetal membranes. The fetal membranes play a central role in the initiation of human parturition, a role that may be subserved in part by quantitative changes in progesterone metabolism. In order to identify and to quantify the metabolites of progesterone produced by the components of the human fetal membranes, amnion and chorion laeve tissues and homogenates were incubated with [3H]progesterone in the presence of added NADPH. The radioactive metabolites, 20alpha-hydroxy-4-pregnen-3-one, 5alpha-pregnane-3,20-dione and 3beta-hydroxy-5alpha-pregnan-20-one, were isolated and identified by derivative formation, a combination of chromatographic techniques, and by crystallization to constant specific activity after addition of authentic standards. A simplified technique of metabolite quantification was developed that involves one thin layer chromatographic procedure and liquid scintillation assay of radioactivity. The accuracy of this method was established by comparison with data obtained using classical techniques. This study demonstrates the presence of human fetal membranes 5alpha-reductase, 20alpha-hydroxysteroid oxidoreductase, and 3beta-hydroxy-steroid oxidoreductase, and a qualitative difference between amnion and chorion laeve."}
{"id": "PMID:20452", "title": "Chromatographic separations of alphavirus strains by hydroxylapatite.", "content": "Hydroxylapatite column chromatography methods were developed to characterize selected alphavirus populations. Different conditions of pH and phosphate molarity were required to obtain satisfactory elution profiles and separations for Western equine encephalomyelitis virus strains, compared with Eastern equine encephalomyelitis virus and Semliki Forest virus strains. Raising the pH of the buffers effected earlier elutions of all viruses. Selection of phosphate gradients with more gentle slopes and adjustment to the proper pH effected better separations of virus subpopulations. Elution profiles were not affected by 0.85% NaCl, 10% fetal calf serum, or 1% bovine serum albumin, which are common constituents of virus-stabilizing diluents. Passage of Western equine encephalomyelitis and Semliki Forest viruses in BHK-21, Vero, or duck embryo cell cultures or in suckling mouse brains did not usually affect elution profiles, unless passage also resulted in a shift in the plaque size marker. Essentially all infectious virus applied to the column was recoverable in appropriate fractions. This permitted accurate determinations of heterogeneity within alphavirus populations. For Western equine encephalomyelitis large-plaque (LP) and small-plaque (SP) virus populations, it was possible to detect ratios of 1 LP in a population of 10(6) SP, and 1 SP in 10(3) LP by using linear phosphate gradients. When stepwise elution procedures were used, it was possible to detect ratios of 1 SP in a population of 10(5) LP. Hydroxylapatite column chromatography therefore appears to be a useful tool for characterizing alphaviruses and for isolating minority subpopulations of viruses of biological or epidemiological importance from apparently homogeneous virus stocks.", "contents": "Chromatographic separations of alphavirus strains by hydroxylapatite. Hydroxylapatite column chromatography methods were developed to characterize selected alphavirus populations. Different conditions of pH and phosphate molarity were required to obtain satisfactory elution profiles and separations for Western equine encephalomyelitis virus strains, compared with Eastern equine encephalomyelitis virus and Semliki Forest virus strains. Raising the pH of the buffers effected earlier elutions of all viruses. Selection of phosphate gradients with more gentle slopes and adjustment to the proper pH effected better separations of virus subpopulations. Elution profiles were not affected by 0.85% NaCl, 10% fetal calf serum, or 1% bovine serum albumin, which are common constituents of virus-stabilizing diluents. Passage of Western equine encephalomyelitis and Semliki Forest viruses in BHK-21, Vero, or duck embryo cell cultures or in suckling mouse brains did not usually affect elution profiles, unless passage also resulted in a shift in the plaque size marker. Essentially all infectious virus applied to the column was recoverable in appropriate fractions. This permitted accurate determinations of heterogeneity within alphavirus populations. For Western equine encephalomyelitis large-plaque (LP) and small-plaque (SP) virus populations, it was possible to detect ratios of 1 LP in a population of 10(6) SP, and 1 SP in 10(3) LP by using linear phosphate gradients. When stepwise elution procedures were used, it was possible to detect ratios of 1 SP in a population of 10(5) LP. Hydroxylapatite column chromatography therefore appears to be a useful tool for characterizing alphaviruses and for isolating minority subpopulations of viruses of biological or epidemiological importance from apparently homogeneous virus stocks."}
{"id": "PMID:20453", "title": "Sonication as a tool for the study of adenylyl cyclase activity.", "content": "The technique of sonication was applied in studying adenylyl cyclase activity of cultured fibroblasts. Exposure of BHK 21 c/13 to brief periods of low power sonication gives cell preparations with greater basal, fluoride and hormone sensitive adenylyl cyclase activites than those of broken cell preparations of homogenized cells. The sonicated cells provide a convenient method to study adenylyl cyclase since they are added directly to the adenylyl cyclase reaction vessels without further processing. Maximal epinephrine stimulated activity in sonicated cells is nearly equivalent to that activated by sodium fluoride, but the apparent affinity of the enzyme system is similar to that of broken cell preparations. Furthermore, broken cell preparations of sonicated cells possess greater adenylyl cyclase activity than broken cell preparations of unsonicated cells. This procedure may provide a useful tool for the analysis of the hormonal regulation of adenylyl cyclase activity of isolated cells.", "contents": "Sonication as a tool for the study of adenylyl cyclase activity. The technique of sonication was applied in studying adenylyl cyclase activity of cultured fibroblasts. Exposure of BHK 21 c/13 to brief periods of low power sonication gives cell preparations with greater basal, fluoride and hormone sensitive adenylyl cyclase activites than those of broken cell preparations of homogenized cells. The sonicated cells provide a convenient method to study adenylyl cyclase since they are added directly to the adenylyl cyclase reaction vessels without further processing. Maximal epinephrine stimulated activity in sonicated cells is nearly equivalent to that activated by sodium fluoride, but the apparent affinity of the enzyme system is similar to that of broken cell preparations. Furthermore, broken cell preparations of sonicated cells possess greater adenylyl cyclase activity than broken cell preparations of unsonicated cells. This procedure may provide a useful tool for the analysis of the hormonal regulation of adenylyl cyclase activity of isolated cells."}
{"id": "PMID:20454", "title": "Blood and tissue distribution of gamma glutamyl transferase in the cow.", "content": "To test the hepatic specificity of gamma-glutamyl transferase in the cow, the tissue distribution of this enzyme was studied in 10 healthy adult cows. It was located mainly in kidney, pancreas, and liver. The relative hepatic specificity of this enzyme indicated that measurement of its activity in serum could be a valuable test of hepatic damage in the cow. The blood activity measured within 54 plasmas and 54 serums of apparently healthy animals was almost the same, 17.7 +/- 5.7 U/liter for plasma and 18.6 +/- 6.2 U/liter for serum.", "contents": "Blood and tissue distribution of gamma glutamyl transferase in the cow. To test the hepatic specificity of gamma-glutamyl transferase in the cow, the tissue distribution of this enzyme was studied in 10 healthy adult cows. It was located mainly in kidney, pancreas, and liver. The relative hepatic specificity of this enzyme indicated that measurement of its activity in serum could be a valuable test of hepatic damage in the cow. The blood activity measured within 54 plasmas and 54 serums of apparently healthy animals was almost the same, 17.7 +/- 5.7 U/liter for plasma and 18.6 +/- 6.2 U/liter for serum."}
{"id": "PMID:20473", "title": "Myxomatosis on the Western Plains of Victoria.", "content": "Myxomatosis on the Western Plains is an enzootic disease in contrast with the epizootic pattern which is general in eastern Australia. The most unusual aspects are the presence of significant numbers of diseased rabbits throughout the winter and the continuously low percentage of rabbits with antibodies to myxoma virus. Climatic and topographic conditions are unsuited to the production of the high densities of mosquitoes necessary for widespread epizootics. Under these conditions the effects of less efficient methods of myxomatosis transmission are apparent. The unusual epidemiology of myxomatosis has resulted in selection for virulence of the virus similar to that which has occurred under summer epizootic conditions. All field strains are now in the mid range of virulence.", "contents": "Myxomatosis on the Western Plains of Victoria. Myxomatosis on the Western Plains is an enzootic disease in contrast with the epizootic pattern which is general in eastern Australia. The most unusual aspects are the presence of significant numbers of diseased rabbits throughout the winter and the continuously low percentage of rabbits with antibodies to myxoma virus. Climatic and topographic conditions are unsuited to the production of the high densities of mosquitoes necessary for widespread epizootics. Under these conditions the effects of less efficient methods of myxomatosis transmission are apparent. The unusual epidemiology of myxomatosis has resulted in selection for virulence of the virus similar to that which has occurred under summer epizootic conditions. All field strains are now in the mid range of virulence."}
{"id": "PMID:20478", "title": "Phenothiazine phototoxicity: toxic chlorpromazine photoproducts.", "content": "The effect of preirradiated chlorpromazine (CPZ) solutions has been studied in vivo in the guinea pig and in vitro in a yeast culture. With intracutaneous administration of CPZ solutions preirradiated with long-wave ultraviolet radiation (UVA), an inflammatory response was attained equaling the response achieved when nonirradiated solutions were injected and the skin of the animals was subsequently irradiated with UVA. Preirradiated CPZ was not toxic to the yeast culture. During irradiation the pH of the CPZ solution changed, indicating an accumulation of acid photoproducts. Nonphototoxic phenothiazines and related tricyclic drugs failed to change their pH following irradiation whereas phototoxic compounds behaved like CPZ. The low pH alone could not account for the inflammatory response in vivo, as neutralized irradiated CPZ solutions still induced inflammation, and acidified, nonirradiated solutions failed to cause a reaction. CPZ phototoxicity seems mainly to be due to the effect of photoproducts. The nature of these is not known, but it is suggested that the stable free radical of CPZ might be an active principle.", "contents": "Phenothiazine phototoxicity: toxic chlorpromazine photoproducts. The effect of preirradiated chlorpromazine (CPZ) solutions has been studied in vivo in the guinea pig and in vitro in a yeast culture. With intracutaneous administration of CPZ solutions preirradiated with long-wave ultraviolet radiation (UVA), an inflammatory response was attained equaling the response achieved when nonirradiated solutions were injected and the skin of the animals was subsequently irradiated with UVA. Preirradiated CPZ was not toxic to the yeast culture. During irradiation the pH of the CPZ solution changed, indicating an accumulation of acid photoproducts. Nonphototoxic phenothiazines and related tricyclic drugs failed to change their pH following irradiation whereas phototoxic compounds behaved like CPZ. The low pH alone could not account for the inflammatory response in vivo, as neutralized irradiated CPZ solutions still induced inflammation, and acidified, nonirradiated solutions failed to cause a reaction. CPZ phototoxicity seems mainly to be due to the effect of photoproducts. The nature of these is not known, but it is suggested that the stable free radical of CPZ might be an active principle."}
{"id": "PMID:20479", "title": "Acute bacterial meningitis at Boston City Hospital during 12 selected years, 1935-1972.", "content": "Data are presented on the occurrence of and mortality rate from acute bacterial meningitis at Boston City Hospital during 12 years between 1935 and 1972 selected in relation to the introduction of potent antibacterial agents. The most frequent causative organisms were Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, but large proportions were caused by other gram-positive cocci and gram-negative bacilli. The greatest reduction in mortality rate after antibiotics became widely used was in patients with meningococcal and influenzal meningitis who were less than or equal to 19 years old. Less striking reductions occurred in cases of other etiologies in patients less than or equal to 59 years old, but in those greater than or equal to 60 years old, the mortality rate remained high, and the proportion of cases of meningitis in that age group more than doubled. Comparisons with similar data on all bacteremic infections are presented.", "contents": "Acute bacterial meningitis at Boston City Hospital during 12 selected years, 1935-1972. Data are presented on the occurrence of and mortality rate from acute bacterial meningitis at Boston City Hospital during 12 years between 1935 and 1972 selected in relation to the introduction of potent antibacterial agents. The most frequent causative organisms were Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, but large proportions were caused by other gram-positive cocci and gram-negative bacilli. The greatest reduction in mortality rate after antibiotics became widely used was in patients with meningococcal and influenzal meningitis who were less than or equal to 19 years old. Less striking reductions occurred in cases of other etiologies in patients less than or equal to 59 years old, but in those greater than or equal to 60 years old, the mortality rate remained high, and the proportion of cases of meningitis in that age group more than doubled. Comparisons with similar data on all bacteremic infections are presented."}
{"id": "PMID:20481", "title": "Some properties of Hb G San Jose (beta7 glu replaced by gly): comparisons with Hb S.", "content": "Hb G San Jose (beta7 glu leads to gly) was studied with respect to oxygen affinity, Bohr effect, surface activity in dilute aqueous solutions, mechanical precipitability, heat stability and its ability to copolymerize in the deoxy form with Hb S. Oxygen affinity, Bohr effect, and polymerization with Hb S were found to be identical to those of Hb A when studied under the same conditions. However, surface activity and mechanical precipitation rates of the oxyconformers closely resembled those of oxyhemoglobin S. Hb G San Jose was also found to be slightly more unstable with heat than Hb A, although the instability was not detected by the usual incubation method of 1 hr at 50 degrees and higher temperatures were needed to elicit this difference. It is concluded that the ability to polymerize and the presence of increased surface activity are distinct and separable attributes of hemoglobin mutants. The finding that mixtures of Hb S and Hb G San Jose gel like mixtures of Hb S and Hb A supports the conclusion that only one beta 6 Val combining site per tetramer is required for polymer formation.", "contents": "Some properties of Hb G San Jose (beta7 glu replaced by gly): comparisons with Hb S. Hb G San Jose (beta7 glu leads to gly) was studied with respect to oxygen affinity, Bohr effect, surface activity in dilute aqueous solutions, mechanical precipitability, heat stability and its ability to copolymerize in the deoxy form with Hb S. Oxygen affinity, Bohr effect, and polymerization with Hb S were found to be identical to those of Hb A when studied under the same conditions. However, surface activity and mechanical precipitation rates of the oxyconformers closely resembled those of oxyhemoglobin S. Hb G San Jose was also found to be slightly more unstable with heat than Hb A, although the instability was not detected by the usual incubation method of 1 hr at 50 degrees and higher temperatures were needed to elicit this difference. It is concluded that the ability to polymerize and the presence of increased surface activity are distinct and separable attributes of hemoglobin mutants. The finding that mixtures of Hb S and Hb G San Jose gel like mixtures of Hb S and Hb A supports the conclusion that only one beta 6 Val combining site per tetramer is required for polymer formation."}
{"id": "PMID:20482", "title": "Effect of dietary fat saturation on acylcoenzyme A:-cholesterol acyltransferase activity of Ehrlich cell microsomes.", "content": "Ehrlich cells grown in mice fed coconut oil diets (highly saturated) contain about twice as much cholesteryl ester as those grown in mice fed sunflower oil diets (highly polyunsaturated). Acylcoenzyme A: cholesterol acyltransferase (ACAT) activity was 30-100% higher in microsomes prepared from the cells grown on coconut oil (M(c)) than in those prepared from the cells grown on sunflower oil (M(s)). Increased ACAT activity was noted in M(c) with either [1-(14)C]palmitoyl CoA or [1,2-(3)H]cholesterol as the labeled substrate. This occurred at all acyl CoA concentrations tested and, in the [1,2-(3)H]cholesterol assay, with palmitoyl, oleoyl, or linoleoyl CoA as the substrate. The pH optimum for ACAT activity was the same with M(c) and M(s), pH 7.0. ACAT activity obeyed Michaelis-Menten kinetics at palmitoyl CoA concentrations between 1 and 10 micro M. Substrate inhibition occurred at higher concentrations. Kinetic analysis with [1-(14)C]palmitoyl CoA as the substrate indicated that the apparent K(m) for M(c) was 33% smaller than for M(s). There was no difference, however, in apparent V(max) values. The cholesterol and phospholipid contents of M(c) and M(s) were similar, but their fatty acid compositions differed considerably. M(c) contained 2.7 times more monoenoic fatty acid and only half as much polyenoic fatty acid as M(s). Our results indicate that dietary modification of the microsomal fatty acid composition is associated with alterations in the activity of ACAT, an enzyme that is tightly bound to the microsomes. These changes in ACAT activity may be partly responsible for the differences in cholesteryl ester contents of Ehrlich cells grown in mice fed the coconut and sunflower oil diets.", "contents": "Effect of dietary fat saturation on acylcoenzyme A:-cholesterol acyltransferase activity of Ehrlich cell microsomes. Ehrlich cells grown in mice fed coconut oil diets (highly saturated) contain about twice as much cholesteryl ester as those grown in mice fed sunflower oil diets (highly polyunsaturated). Acylcoenzyme A: cholesterol acyltransferase (ACAT) activity was 30-100% higher in microsomes prepared from the cells grown on coconut oil (M(c)) than in those prepared from the cells grown on sunflower oil (M(s)). Increased ACAT activity was noted in M(c) with either [1-(14)C]palmitoyl CoA or [1,2-(3)H]cholesterol as the labeled substrate. This occurred at all acyl CoA concentrations tested and, in the [1,2-(3)H]cholesterol assay, with palmitoyl, oleoyl, or linoleoyl CoA as the substrate. The pH optimum for ACAT activity was the same with M(c) and M(s), pH 7.0. ACAT activity obeyed Michaelis-Menten kinetics at palmitoyl CoA concentrations between 1 and 10 micro M. Substrate inhibition occurred at higher concentrations. Kinetic analysis with [1-(14)C]palmitoyl CoA as the substrate indicated that the apparent K(m) for M(c) was 33% smaller than for M(s). There was no difference, however, in apparent V(max) values. The cholesterol and phospholipid contents of M(c) and M(s) were similar, but their fatty acid compositions differed considerably. M(c) contained 2.7 times more monoenoic fatty acid and only half as much polyenoic fatty acid as M(s). Our results indicate that dietary modification of the microsomal fatty acid composition is associated with alterations in the activity of ACAT, an enzyme that is tightly bound to the microsomes. These changes in ACAT activity may be partly responsible for the differences in cholesteryl ester contents of Ehrlich cells grown in mice fed the coconut and sunflower oil diets."}
{"id": "PMID:20483", "title": "Effect of sodium valproate on plasma protein binding of diphenylhydantoin.", "content": "In vivo and in vitro experimental data are presented in support of the hypothesis that sodium valproate displaces diphenylhydantoin (DPH) from plasma protein binding sites. This interaction could have important practical implications in the management of patients on combined therapy with these two drugs. Acute neurological features of DPH intoxication may be precipitated as a result of an increased free (pharmacologically active) fraction, which would not be detected by routine plasma DPH estimations since these reflects largely the bound fraction.", "contents": "Effect of sodium valproate on plasma protein binding of diphenylhydantoin. In vivo and in vitro experimental data are presented in support of the hypothesis that sodium valproate displaces diphenylhydantoin (DPH) from plasma protein binding sites. This interaction could have important practical implications in the management of patients on combined therapy with these two drugs. Acute neurological features of DPH intoxication may be precipitated as a result of an increased free (pharmacologically active) fraction, which would not be detected by routine plasma DPH estimations since these reflects largely the bound fraction."}
{"id": "PMID:20485", "title": "Mouse spinal cord in cell culture. III. Neuronal chemosensitivity and its relationship to synaptic activity.", "content": "1. Mouse spinal cord (SC) cells in dissociated cell cultures showed strong electrophysiologic responses to glutamate, gamma-aminobutyric acid (GABA), and glycine when these were iontophoretically applied to the neurons. 2. The extrapolated reversal potential for the glutamate response was 20-30 mV negative in contrast to the positive extrapolated reversal potential for the SC-SC excitatory postsynaptic potential. The data are interpreted as indicating different ionic mechanisms for the glutamate response and the EPSP. 3. The reversal potentials for the glycine and GABA responses were similar to one another and to the IPSP reversal potential. The time course of the glycine and GABA responses were quite different from each other, however. 4. While some SC cells showed a relatively uniform sensitivity over their surfaces to iontophoretically applied glutamate, discrete regions of higher sensitivity occurred on most cells. 5. Release of excitatory and inhibitory transmitter could be elicited by focal application of glutamate and, in favorable instances, this could be shown to be due to the sensitivity of presynaptic terminals to the applied glutamate. Considerable spatial resolution of regions from which transmitter release could be elicited was achieved by this technique. Some correspondence between glutamate \"hot spots\" and such release sites was found.", "contents": "Mouse spinal cord in cell culture. III. Neuronal chemosensitivity and its relationship to synaptic activity. 1. Mouse spinal cord (SC) cells in dissociated cell cultures showed strong electrophysiologic responses to glutamate, gamma-aminobutyric acid (GABA), and glycine when these were iontophoretically applied to the neurons. 2. The extrapolated reversal potential for the glutamate response was 20-30 mV negative in contrast to the positive extrapolated reversal potential for the SC-SC excitatory postsynaptic potential. The data are interpreted as indicating different ionic mechanisms for the glutamate response and the EPSP. 3. The reversal potentials for the glycine and GABA responses were similar to one another and to the IPSP reversal potential. The time course of the glycine and GABA responses were quite different from each other, however. 4. While some SC cells showed a relatively uniform sensitivity over their surfaces to iontophoretically applied glutamate, discrete regions of higher sensitivity occurred on most cells. 5. Release of excitatory and inhibitory transmitter could be elicited by focal application of glutamate and, in favorable instances, this could be shown to be due to the sensitivity of presynaptic terminals to the applied glutamate. Considerable spatial resolution of regions from which transmitter release could be elicited was achieved by this technique. Some correspondence between glutamate \"hot spots\" and such release sites was found."}
{"id": "PMID:20486", "title": "Early effects of hypervitaminosis A on gluconeogenic activity and amino acid metabolizing enzymes of rat liver.", "content": "In an earlier report from this laboratory, one of the early manifestations of hypervitaminosis A was shown to be a marked stimulation of hepatic gluconeogenesis. In the present study, effects of feeding 30,000 IU of retinyl palmitate to young rats (80-100 g), once daily, for 2 days on the incorporation of 14C-labeled precursors into glucose and glycogen by liver slices, levels of amino acids in blood and tissues, and activities of some important amino acid catabolizing enzymes in the liver were investigated. A stimulation of hepatic gluconeogenesis in hypervitaminosis A was indicated by the increased incorporation of 14C-labeled alanine and bicarbonate into glucose and glycogen by liver slices. Excessive intake of retinol caused a marked increase in the activities of hepatic alanine aminotransferase and ornithine aminotransferase and a decrease in that of tryptophan pyrrolase, without affecting those of tyrosine aminotransferase and serine dehydratase. The ratio of NADH:NAD in the livers of rats fed excess retinol was significantly increased. It is suggested that enhancement of glucoeogenesis in hypervitaminosis A is caused by a stimulation of gluconeogenic activity of the liver.", "contents": "Early effects of hypervitaminosis A on gluconeogenic activity and amino acid metabolizing enzymes of rat liver. In an earlier report from this laboratory, one of the early manifestations of hypervitaminosis A was shown to be a marked stimulation of hepatic gluconeogenesis. In the present study, effects of feeding 30,000 IU of retinyl palmitate to young rats (80-100 g), once daily, for 2 days on the incorporation of 14C-labeled precursors into glucose and glycogen by liver slices, levels of amino acids in blood and tissues, and activities of some important amino acid catabolizing enzymes in the liver were investigated. A stimulation of hepatic gluconeogenesis in hypervitaminosis A was indicated by the increased incorporation of 14C-labeled alanine and bicarbonate into glucose and glycogen by liver slices. Excessive intake of retinol caused a marked increase in the activities of hepatic alanine aminotransferase and ornithine aminotransferase and a decrease in that of tryptophan pyrrolase, without affecting those of tyrosine aminotransferase and serine dehydratase. The ratio of NADH:NAD in the livers of rats fed excess retinol was significantly increased. It is suggested that enhancement of glucoeogenesis in hypervitaminosis A is caused by a stimulation of gluconeogenic activity of the liver."}
{"id": "PMID:20487", "title": "Sites of organic acid production and patterns of digesta movement in the gastrointestinal tract of the rock hyrax.", "content": "The rock hyrax, smallest of the present day ungulates and a near relative of the elephant, has a gastrointestinal tract of such complex nature that it may be considered ccomparable to both the simple and complex stomach mammals, and also to birds. They have a stomach to body weight capacity equal to that of sheep. But for all its complexity, the passage of ingesta is reasonably rapid. However, there are three major sites of digesta retention and microbial fermentation of the ingested material. The cranial stomach provides the first major site of fermentation with VFA levels comparable to those observed in the rumen (125-145 mM/liter). Quantities of lactic acid are also produced in the foregut where the pH may vary from 2 to 5.5. The ingested particulate material is exclusively retained in the cranial half of the stomach for 4 hours after consumption, and partially retained in the entire stomach for greater than 24 hours. The mid-gut sacculation provides the second major site of fermentation with the retention of the digesta in this gut segment for up to 16 hours. The two ceca provide the third site. Concentrations of VFA in these latter two gut segments approaches 80 mM/liter, while the near stable and neutral pH corresponds to the absence of lactic acid production.", "contents": "Sites of organic acid production and patterns of digesta movement in the gastrointestinal tract of the rock hyrax. The rock hyrax, smallest of the present day ungulates and a near relative of the elephant, has a gastrointestinal tract of such complex nature that it may be considered ccomparable to both the simple and complex stomach mammals, and also to birds. They have a stomach to body weight capacity equal to that of sheep. But for all its complexity, the passage of ingesta is reasonably rapid. However, there are three major sites of digesta retention and microbial fermentation of the ingested material. The cranial stomach provides the first major site of fermentation with VFA levels comparable to those observed in the rumen (125-145 mM/liter). Quantities of lactic acid are also produced in the foregut where the pH may vary from 2 to 5.5. The ingested particulate material is exclusively retained in the cranial half of the stomach for 4 hours after consumption, and partially retained in the entire stomach for greater than 24 hours. The mid-gut sacculation provides the second major site of fermentation with the retention of the digesta in this gut segment for up to 16 hours. The two ceca provide the third site. Concentrations of VFA in these latter two gut segments approaches 80 mM/liter, while the near stable and neutral pH corresponds to the absence of lactic acid production."}
{"id": "PMID:20491", "title": "Vehicle effects on ocular drug bioavailability II: Evaluation of pilocarpine.", "content": "The influence of vehicle composition on ocular penetration of pilocarpine was studied in the albino rabbit. Increasing the pH of a vehicle promoted increased corneal penetration for pilocarpine, in accordance with the pH-partition hypothesis, but a similar series of experiments with a nonionizable drug, glycerin, gave similar results. The extent of pH-induced lacrimation by the vehicle and its effect on precorneal drug concentration also was determined. Increased pilocarpine absorption at neutral to slightly alkaline pH was due primarily to its peculiar solubility characteristics coupled with less irritation and lacrimation rather than a direct pH effect on the molecule. Incorporation of pilocarpine into a petrolatum-based ointment vehicle resulted in increased aqueous humor pilocarpine levels above those provided by an equivalent dose of aqueous solution. The mechanism of this increase was determined to be a higher effective concentration of pilocarpine in the ointment vehicle coupled with an increase in contact time of the dose. The ointment system also exerted an unusual form of vehicle control in that it promoted the corneal penetration of pilocarpine while impeding uniform mixing of the dose with tears and thereby imposed a restriction on the amount of pilocarpine available to the ocular tissues.", "contents": "Vehicle effects on ocular drug bioavailability II: Evaluation of pilocarpine. The influence of vehicle composition on ocular penetration of pilocarpine was studied in the albino rabbit. Increasing the pH of a vehicle promoted increased corneal penetration for pilocarpine, in accordance with the pH-partition hypothesis, but a similar series of experiments with a nonionizable drug, glycerin, gave similar results. The extent of pH-induced lacrimation by the vehicle and its effect on precorneal drug concentration also was determined. Increased pilocarpine absorption at neutral to slightly alkaline pH was due primarily to its peculiar solubility characteristics coupled with less irritation and lacrimation rather than a direct pH effect on the molecule. Incorporation of pilocarpine into a petrolatum-based ointment vehicle resulted in increased aqueous humor pilocarpine levels above those provided by an equivalent dose of aqueous solution. The mechanism of this increase was determined to be a higher effective concentration of pilocarpine in the ointment vehicle coupled with an increase in contact time of the dose. The ointment system also exerted an unusual form of vehicle control in that it promoted the corneal penetration of pilocarpine while impeding uniform mixing of the dose with tears and thereby imposed a restriction on the amount of pilocarpine available to the ocular tissues."}
{"id": "PMID:20492", "title": "Everted rat intestinal sacs as an in vitro model for assessing absorptivity of new drugs.", "content": "An in vitro model that utilizes everted rat intestinal sacs was evaluated for assessing the absorptivity of several analogs of potential drug substances prior to formulation work and clinical trials. This model not only is a useful qualitative tool for assessing absorptivity of structurally related compounds but also yields some insight into the process involved in drug absorption. Notwithstanding the complexities involved in the absorption processes, the data support the hypothesis that the absorption of organic electrolytes mainly takes place by the partitioning of the unionized species into the lipoidal membranes and then diffusion.", "contents": "Everted rat intestinal sacs as an in vitro model for assessing absorptivity of new drugs. An in vitro model that utilizes everted rat intestinal sacs was evaluated for assessing the absorptivity of several analogs of potential drug substances prior to formulation work and clinical trials. This model not only is a useful qualitative tool for assessing absorptivity of structurally related compounds but also yields some insight into the process involved in drug absorption. Notwithstanding the complexities involved in the absorption processes, the data support the hypothesis that the absorption of organic electrolytes mainly takes place by the partitioning of the unionized species into the lipoidal membranes and then diffusion."}
{"id": "PMID:20494", "title": "Characteristics of medicated and unmedicated microglobules recovered from complex coacervates of gelatin-acacia.", "content": "Medicated and unmedicated microglobules prepared from complex coacervates of Type A gelatin and acacia were recovered as water-insoluble powders consisting of discrete units, which were spontaneously revertible to highly disperse systems when suspended in water or physiological electrolyte solutions. Spherical microglobules containing up to 15% (w/w) sulfamerazine had a nominal diameter of 30 micron in aqueous suspension. Larger but irregularly shaped products containing up to 45% (w/w) sulfamerazine were also recovered. The relationships of the weight of sulfamerazine added per coacervate batch to weight yield and percent (w/w) included sulfamerazine of the microglobules were both linear.", "contents": "Characteristics of medicated and unmedicated microglobules recovered from complex coacervates of gelatin-acacia. Medicated and unmedicated microglobules prepared from complex coacervates of Type A gelatin and acacia were recovered as water-insoluble powders consisting of discrete units, which were spontaneously revertible to highly disperse systems when suspended in water or physiological electrolyte solutions. Spherical microglobules containing up to 15% (w/w) sulfamerazine had a nominal diameter of 30 micron in aqueous suspension. Larger but irregularly shaped products containing up to 45% (w/w) sulfamerazine were also recovered. The relationships of the weight of sulfamerazine added per coacervate batch to weight yield and percent (w/w) included sulfamerazine of the microglobules were both linear."}
{"id": "PMID:20495", "title": "In vitro adsorption of doxorubicin hydrochloride on insoluble calcium phosphate.", "content": "The adsorption of doxorubicin hydrochloride, a potent antitumor agent, on solid tribasic calcium phosphate was studied in vitro. A Langmuir adsorption isotherm at pH 7.4 and the maximum adsorption capacity of tribasic calcium phosphate were established. Tribasic calcium phosphate was chosen as a model for solid bone samples, which are stained with doxorubicin in patients who have received long-term doxorubicin therapy.", "contents": "In vitro adsorption of doxorubicin hydrochloride on insoluble calcium phosphate. The adsorption of doxorubicin hydrochloride, a potent antitumor agent, on solid tribasic calcium phosphate was studied in vitro. A Langmuir adsorption isotherm at pH 7.4 and the maximum adsorption capacity of tribasic calcium phosphate were established. Tribasic calcium phosphate was chosen as a model for solid bone samples, which are stained with doxorubicin in patients who have received long-term doxorubicin therapy."}
{"id": "PMID:20497", "title": "Mechanism of isoproterenol-induced desensitization of tracheal smooth muscle.", "content": "Isolated rat tracheal smooth muscle became considerably less sensitive to the relaxing action of isoproterenol after being incubated with 5 x 10(-6) M isoproterenol for 30 minutes. Pretreatment of the tissue with propranolol, but not with methylprednisolone, clearly reduced the isoproterenol-induced desensitization. This suggested that propranolol by occupying the beta adrenergic receptor prevented isoproterenol from binding to this receptor, thereby preventing the isoproterenol-induced desensitization. Furthermore, an isoproterenol-desensitized tracheal preparation exhibited a diminished sensitivity to other beta agonists, but not to the spasmolytic actions of D600, hydralazine, sodium nitrite and aminophylline. These results suggested that the beta receptor is specifically involved in the desensitization induced by isoproterenol. A highly desensitized tissue could always be made to undergo complete relaxation by exposing it to sufficiently high concentrations of isoproterenol. Thus, there appeared to be no positive indication of a very large change in the apparent intrinsic activity of the isoproterenol in the desensitized tissue. However, the dissociation constant for the propranolol-beta receptor complex in the desensitized tissue was shown to be 180-fold larger than that in the normal tissue. These findings provide strong evidence that one demonstrable cellular change that occurs in the desensitized tissue is a pronounced reduction in the affinity of the beta receptors for isoproterenol.", "contents": "Mechanism of isoproterenol-induced desensitization of tracheal smooth muscle. Isolated rat tracheal smooth muscle became considerably less sensitive to the relaxing action of isoproterenol after being incubated with 5 x 10(-6) M isoproterenol for 30 minutes. Pretreatment of the tissue with propranolol, but not with methylprednisolone, clearly reduced the isoproterenol-induced desensitization. This suggested that propranolol by occupying the beta adrenergic receptor prevented isoproterenol from binding to this receptor, thereby preventing the isoproterenol-induced desensitization. Furthermore, an isoproterenol-desensitized tracheal preparation exhibited a diminished sensitivity to other beta agonists, but not to the spasmolytic actions of D600, hydralazine, sodium nitrite and aminophylline. These results suggested that the beta receptor is specifically involved in the desensitization induced by isoproterenol. A highly desensitized tissue could always be made to undergo complete relaxation by exposing it to sufficiently high concentrations of isoproterenol. Thus, there appeared to be no positive indication of a very large change in the apparent intrinsic activity of the isoproterenol in the desensitized tissue. However, the dissociation constant for the propranolol-beta receptor complex in the desensitized tissue was shown to be 180-fold larger than that in the normal tissue. These findings provide strong evidence that one demonstrable cellular change that occurs in the desensitized tissue is a pronounced reduction in the affinity of the beta receptors for isoproterenol."}
{"id": "PMID:20498", "title": "Effect of dipivalyl derivatives of catecholamines on cardiovascular function in the conscious dog.", "content": "Dipivalyl derivatives of epinephrine, norepinephrine and isoproterenol were injected intravenously into conscious dogs while cardiovascular variables were monitored. The dipivalyl compounds produced cardiovascular effects that were comparable to those produced by their respective parent catecholamines except that the responses had a delayed onset and a prolonged duration. The catecholamines were more potent than their derivatives; norepinephrine was 28 times, epinephrine 15 times and isoproterenol 1.7 times as effective as their respective dipivalyl derivatives. Alpha or beta adrenergic responses to the dipivalyl compounds were attenuated or abolished after alpha adrenergic blockade (phenoxybenzamine or phentolamine), or beta adrenergic blockade (propranolol), respectively, or combined alpha and beta blockade. Since other evidence indicates that the dipivalyl derivatives themselves are inactive, our results suggest that these compounds act as prodrugs that exert their cardiovascular effects only after they are biotransformed to catecholamines.", "contents": "Effect of dipivalyl derivatives of catecholamines on cardiovascular function in the conscious dog. Dipivalyl derivatives of epinephrine, norepinephrine and isoproterenol were injected intravenously into conscious dogs while cardiovascular variables were monitored. The dipivalyl compounds produced cardiovascular effects that were comparable to those produced by their respective parent catecholamines except that the responses had a delayed onset and a prolonged duration. The catecholamines were more potent than their derivatives; norepinephrine was 28 times, epinephrine 15 times and isoproterenol 1.7 times as effective as their respective dipivalyl derivatives. Alpha or beta adrenergic responses to the dipivalyl compounds were attenuated or abolished after alpha adrenergic blockade (phenoxybenzamine or phentolamine), or beta adrenergic blockade (propranolol), respectively, or combined alpha and beta blockade. Since other evidence indicates that the dipivalyl derivatives themselves are inactive, our results suggest that these compounds act as prodrugs that exert their cardiovascular effects only after they are biotransformed to catecholamines."}
{"id": "PMID:20499", "title": "Effect of changing the composition of the bathing solutions upon the isometric tension-pCa relationship in bundles of crustacean myofibrils.", "content": "1. The relative isometric tension-pCa relationship has been determined for isolated bundles of barnacle myofibrils under a variety of ionic conditions using [Ca(2+)]-buffered solutions which also contained an ATP regenerating system (creatine phosphate and creatine kinase).2. The results are in better agreement with the ;consecutive' scheme of reaction rather than with the ;independent' alternative (Ashley & Moisescu, 1972) for the co-operative action of two Ca(2+) ions in the process of tension activation in crustacean skeletal muscle.3. Variations in the pH of the activating solutions did have a marked effect on the relative tension-Ca curve, although no effect was observed on the absolute maximum value for isometric tension. A shift in pH by 0.5 u. in the range 6.6-7.6 shifted the Ca(2+)-activation curve by 0.5 log u. towards lower free Ca(2+) concentrations.4. Changes in the free Mg(2+) concentration of the activating solutions in the millimolar range produced a pronounced shift of the relative tension-pCa curve along the pCa axis. Increasing [Mg(2+)] from 1 to 5 mM shifted the curve by about 0.7 log u. to higher free Ca(2+) concentrations, without significantly modifying its steepness.5. Changes in the MgATP concentration of the activating solutions in the range of 1-13 mM had no significant effect on the relative tension-pCa relationship.6. Varying the K(+) concentration in the activating solutions was also observed to have a marked effect upon the tension-pCa relationship in barnacle. An increase in the K(+) concentration from 90 to 170 mM shifted the curve by some 0.6 log u. towards higher free Ca(2+) concentrations.7. Cooling the standard activating solutions from room temperature to +4 degrees C made no apparent difference to the relative tension-pCa relationship, but decreased significantly the absolute tension responses.8. The results presented show that tonicity by itself has a marked effect upon the absolute steady-state tension levels in isolated bundles of myofibrils.9. Maximum isometric tension in this preparation was not simply related to ionic strength, or to the monovalent cation concentration, but it depended, as well, upon the anionic composition of the activating solution. In addition, a change in ionic strength of 25 mM over the range of 245-270 mM did not appear to modify the relative tension-pCa relationship.10. The effect of the physiologically occurring cations H(+), K(+), Mg(2+) upon the relative isometric tension-pCa relationship can be accounted for on the basis of a model of competitive inhibition between these cations and Ca(2+) for the functional unit for tension. This inhibitory effect appears to involve at least one H(+), one Mg(2+) and two K(+) per each Ca(2+) ion participating in the activation process of the functional unit for tension.", "contents": "Effect of changing the composition of the bathing solutions upon the isometric tension-pCa relationship in bundles of crustacean myofibrils. 1. The relative isometric tension-pCa relationship has been determined for isolated bundles of barnacle myofibrils under a variety of ionic conditions using [Ca(2+)]-buffered solutions which also contained an ATP regenerating system (creatine phosphate and creatine kinase).2. The results are in better agreement with the ;consecutive' scheme of reaction rather than with the ;independent' alternative (Ashley & Moisescu, 1972) for the co-operative action of two Ca(2+) ions in the process of tension activation in crustacean skeletal muscle.3. Variations in the pH of the activating solutions did have a marked effect on the relative tension-Ca curve, although no effect was observed on the absolute maximum value for isometric tension. A shift in pH by 0.5 u. in the range 6.6-7.6 shifted the Ca(2+)-activation curve by 0.5 log u. towards lower free Ca(2+) concentrations.4. Changes in the free Mg(2+) concentration of the activating solutions in the millimolar range produced a pronounced shift of the relative tension-pCa curve along the pCa axis. Increasing [Mg(2+)] from 1 to 5 mM shifted the curve by about 0.7 log u. to higher free Ca(2+) concentrations, without significantly modifying its steepness.5. Changes in the MgATP concentration of the activating solutions in the range of 1-13 mM had no significant effect on the relative tension-pCa relationship.6. Varying the K(+) concentration in the activating solutions was also observed to have a marked effect upon the tension-pCa relationship in barnacle. An increase in the K(+) concentration from 90 to 170 mM shifted the curve by some 0.6 log u. towards higher free Ca(2+) concentrations.7. Cooling the standard activating solutions from room temperature to +4 degrees C made no apparent difference to the relative tension-pCa relationship, but decreased significantly the absolute tension responses.8. The results presented show that tonicity by itself has a marked effect upon the absolute steady-state tension levels in isolated bundles of myofibrils.9. Maximum isometric tension in this preparation was not simply related to ionic strength, or to the monovalent cation concentration, but it depended, as well, upon the anionic composition of the activating solution. In addition, a change in ionic strength of 25 mM over the range of 245-270 mM did not appear to modify the relative tension-pCa relationship.10. The effect of the physiologically occurring cations H(+), K(+), Mg(2+) upon the relative isometric tension-pCa relationship can be accounted for on the basis of a model of competitive inhibition between these cations and Ca(2+) for the functional unit for tension. This inhibitory effect appears to involve at least one H(+), one Mg(2+) and two K(+) per each Ca(2+) ion participating in the activation process of the functional unit for tension."}
{"id": "PMID:20500", "title": "Daily changes in the blood of conscious pigs with catheters in foetal and uterine vessels during late gestation.", "content": "1. Catheters were inserted into the foetal carotid artery and maternal middle uterine artery and vein in twenty foetuses from fifteen sows, 91-105 days pregnant. Blood samples were collected from foetal and maternal circulations for periods of 7-21 days after surgery.2. Blood gas tensions, pH, packed cell volume (PCV) and the levels of glucose, fructose and lactic acid in conscious pigs were followed in foetal and maternal bloods during late pregnancy.3. Foetal blood gas tensions, pH, PCV, lactic acid and glucose levels did not change markedly during the last 20-25 days of gestation. Blood fructose concentration fell during this period with the greatest change occurring after 100 days gestation. Foetal and maternal blood pH values were higher than those reported in the sheep, cow, mare and rhesus monkey.4. Small changes in P(CO2) and pH in foetal carotid blood were associated with similar changes in maternal uterine venous blood, so that gradients between sow and foetus remained relatively constant.5. Daily changes in maternal blood glucose levels were associated with smaller changes in foetal blood glucose and fructose levels. Blood glucose concentrations in foetal blood were generally 40-70% of maternal concentrations. Over-all relationships between maternal blood glucose and foetal blood fructose concentrations were masked by the independent fall in foetal fructose levels with age.6. The present findings have been compared with previous observations on acute, anaesthetized preparations in pigs, and chronic preparations in other domestic animals.", "contents": "Daily changes in the blood of conscious pigs with catheters in foetal and uterine vessels during late gestation. 1. Catheters were inserted into the foetal carotid artery and maternal middle uterine artery and vein in twenty foetuses from fifteen sows, 91-105 days pregnant. Blood samples were collected from foetal and maternal circulations for periods of 7-21 days after surgery.2. Blood gas tensions, pH, packed cell volume (PCV) and the levels of glucose, fructose and lactic acid in conscious pigs were followed in foetal and maternal bloods during late pregnancy.3. Foetal blood gas tensions, pH, PCV, lactic acid and glucose levels did not change markedly during the last 20-25 days of gestation. Blood fructose concentration fell during this period with the greatest change occurring after 100 days gestation. Foetal and maternal blood pH values were higher than those reported in the sheep, cow, mare and rhesus monkey.4. Small changes in P(CO2) and pH in foetal carotid blood were associated with similar changes in maternal uterine venous blood, so that gradients between sow and foetus remained relatively constant.5. Daily changes in maternal blood glucose levels were associated with smaller changes in foetal blood glucose and fructose levels. Blood glucose concentrations in foetal blood were generally 40-70% of maternal concentrations. Over-all relationships between maternal blood glucose and foetal blood fructose concentrations were masked by the independent fall in foetal fructose levels with age.6. The present findings have been compared with previous observations on acute, anaesthetized preparations in pigs, and chronic preparations in other domestic animals."}
{"id": "PMID:20501", "title": "Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle.", "content": "1. Ion-sensitive electrodes (made with a chloride-sensitive ion-exchange resin) were used to measure the internal chloride activity (a(i) (Cl)) of frog sartorius fibres at 25 degrees C.2. The internal pH (pH(i)) of other sartorius fibres was measured with a recessed tip pH-sensitive electrode (made with pH-sensitive glass).3. In normal bicarbonate-free solution (containing 2.5 mM potassium), the average chloride equilibrium potential, E(Cl) (calculated from a(i) (Cl) and the measured chloride activity of the external solution (a(o) (Cl)) was 87.7 +/- 1.7 mV (mean +/- S.E.; n = 16) in fibres where the average membrane potential, E(m), was 88.3 +/- 1.5 mV (mean +/- S.E.; n = 16). In experiments where a(i) (Cl) was varied between about 1 and 10 mM (which corresponds to values of E(m) between about -105 and -50 mV) E(Cl) was within 1-3 mV of E(m) at equilibrium. These measurements of a(i) (Cl) were obtained from the potential difference between the chloride-sensitive electrode and an intracellular indifferent micro-electrode filled with potassium chloride. If a potassium sulphate-filled indifferent micro-electrode was used, then values of a(i) (Cl) below about 5 mM were erroneously high, probably due to interference from other sarcoplasmic ions at the indifferent electrode.4. In solutions containing 15 mM bicarbonate and gassed with 5% CO(2), pH(i) was 6.9, corresponding to an internal bicarbonate concentration of 7.6 mM. E(Cl) measured in this solution was some 4 mV positive to E(m). Most of the difference between E(Cl) and E(m) could be ascribed to interference by sarcoplasmic bicarbonate on the basis of selectivity measurements of chloride against bicarbonate made on the ion-exchange resin in the relevant range of a(Cl).5. If bicarbonate/CO(2) in the external solution was replaced by HEPES/pure O(2) at constant pH, then pH(i) rose from 6.88 +/- 0.02 (mean +/- S.E.) to 7.05 +/- 0.02. A change in external pH of 1 unit caused pH(i) to change by about 0.02 unit and the intracellular buffering power was calculated to be about 35.6. In solution made hypertonic by the addition of sucrose, E(m) changed little or depolarized and E(Cl) and E(m) remained close. In contrast, in solution made hypertonic by the addition of solid sodium chloride (high-chloride solution) E(Cl) became negative to E(m). Conversely in low chloride solution E(Cl) became positive to E(m).7. When the chloride permeability (P(Cl)) was reduced by the use of acid solution, E(Cl) moved positive to E(m) indicating an accumulation of internal chloride. When P(Cl) was increased again by returning to more alkaline solution, E(m) depolarized to E(Cl).8. The results are consistent with the existence of a small, active movement of chloride, the effects of which are normally obscured by large passive movements of chloride when P(Cl) is large.", "contents": "Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle. 1. Ion-sensitive electrodes (made with a chloride-sensitive ion-exchange resin) were used to measure the internal chloride activity (a(i) (Cl)) of frog sartorius fibres at 25 degrees C.2. The internal pH (pH(i)) of other sartorius fibres was measured with a recessed tip pH-sensitive electrode (made with pH-sensitive glass).3. In normal bicarbonate-free solution (containing 2.5 mM potassium), the average chloride equilibrium potential, E(Cl) (calculated from a(i) (Cl) and the measured chloride activity of the external solution (a(o) (Cl)) was 87.7 +/- 1.7 mV (mean +/- S.E.; n = 16) in fibres where the average membrane potential, E(m), was 88.3 +/- 1.5 mV (mean +/- S.E.; n = 16). In experiments where a(i) (Cl) was varied between about 1 and 10 mM (which corresponds to values of E(m) between about -105 and -50 mV) E(Cl) was within 1-3 mV of E(m) at equilibrium. These measurements of a(i) (Cl) were obtained from the potential difference between the chloride-sensitive electrode and an intracellular indifferent micro-electrode filled with potassium chloride. If a potassium sulphate-filled indifferent micro-electrode was used, then values of a(i) (Cl) below about 5 mM were erroneously high, probably due to interference from other sarcoplasmic ions at the indifferent electrode.4. In solutions containing 15 mM bicarbonate and gassed with 5% CO(2), pH(i) was 6.9, corresponding to an internal bicarbonate concentration of 7.6 mM. E(Cl) measured in this solution was some 4 mV positive to E(m). Most of the difference between E(Cl) and E(m) could be ascribed to interference by sarcoplasmic bicarbonate on the basis of selectivity measurements of chloride against bicarbonate made on the ion-exchange resin in the relevant range of a(Cl).5. If bicarbonate/CO(2) in the external solution was replaced by HEPES/pure O(2) at constant pH, then pH(i) rose from 6.88 +/- 0.02 (mean +/- S.E.) to 7.05 +/- 0.02. A change in external pH of 1 unit caused pH(i) to change by about 0.02 unit and the intracellular buffering power was calculated to be about 35.6. In solution made hypertonic by the addition of sucrose, E(m) changed little or depolarized and E(Cl) and E(m) remained close. In contrast, in solution made hypertonic by the addition of solid sodium chloride (high-chloride solution) E(Cl) became negative to E(m). Conversely in low chloride solution E(Cl) became positive to E(m).7. When the chloride permeability (P(Cl)) was reduced by the use of acid solution, E(Cl) moved positive to E(m) indicating an accumulation of internal chloride. When P(Cl) was increased again by returning to more alkaline solution, E(m) depolarized to E(Cl).8. The results are consistent with the existence of a small, active movement of chloride, the effects of which are normally obscured by large passive movements of chloride when P(Cl) is large."}
{"id": "PMID:20502", "title": "beta-Adrenergic blocking agents. 16. 1-(Acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols.", "content": "The synthesis of a series of 1-(acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols is described. The compounds were screened as beta-adrenergic receptor antagonists in cats and their partial agonist activity was evaluated in rats depleted of circulating catecholamines. Some of the compounds have a pharmacological profile similar to atenolol. Their structure-activity relationships are discussed.", "contents": "beta-Adrenergic blocking agents. 16. 1-(Acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols. The synthesis of a series of 1-(acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols is described. The compounds were screened as beta-adrenergic receptor antagonists in cats and their partial agonist activity was evaluated in rats depleted of circulating catecholamines. Some of the compounds have a pharmacological profile similar to atenolol. Their structure-activity relationships are discussed."}
{"id": "PMID:20503", "title": "Adrenerigic agents. 7.1 Synthesis and beta-adrenergic agonist activity of several 2-pyridylethanolamines.", "content": "In a search for new selective bronchodilators, three 2-pyridylethanolamines, i.e., 2-tert-butylamino-1-(5-hydroxy-2-pyridyl)ethanol (2b), a related 6-methylsulfonylmethyl (2c), and, a 6-methyl (2d) derivative, were prepared. These compounds were examined for potential bronchodilator activity in an in vitro test for relaxation of guinea pig tracheal tissue. Potential cardiac stimulant activity was evaluated in vitro by measuring changes in the rate of spontaneously beating guinea pig right atrial muscle. Comparison of potency in the tracheal test relative to that in the atrial procedure provides a measure of selectivity. Results of this study indicate that replacement of the phenyl ring of a para-hydroxylated phenylethanolamine with a 2-pyridyl system generally results in compounds which retain a high order of potency in the tracheal test; however, selectivity for tracheobronchial vs. cardiac tissue is markedly greater for the pyridyl derivatives. The alpha-picoline, 2-tert-butylamino-1-(5-hydroxy-6-methyl-2-pyridyl) ethanol (2d), which bears labile protons at a position meta to the ethanolamine side chain, was about equipotent with the corresponding 6-unsubstituted relative 2b. The reason for the failure of these apparently appropriately located labile protons to enhance beta-adrenoreceptor agonist activity is uncertain.", "contents": "Adrenerigic agents. 7.1 Synthesis and beta-adrenergic agonist activity of several 2-pyridylethanolamines. In a search for new selective bronchodilators, three 2-pyridylethanolamines, i.e., 2-tert-butylamino-1-(5-hydroxy-2-pyridyl)ethanol (2b), a related 6-methylsulfonylmethyl (2c), and, a 6-methyl (2d) derivative, were prepared. These compounds were examined for potential bronchodilator activity in an in vitro test for relaxation of guinea pig tracheal tissue. Potential cardiac stimulant activity was evaluated in vitro by measuring changes in the rate of spontaneously beating guinea pig right atrial muscle. Comparison of potency in the tracheal test relative to that in the atrial procedure provides a measure of selectivity. Results of this study indicate that replacement of the phenyl ring of a para-hydroxylated phenylethanolamine with a 2-pyridyl system generally results in compounds which retain a high order of potency in the tracheal test; however, selectivity for tracheobronchial vs. cardiac tissue is markedly greater for the pyridyl derivatives. The alpha-picoline, 2-tert-butylamino-1-(5-hydroxy-6-methyl-2-pyridyl) ethanol (2d), which bears labile protons at a position meta to the ethanolamine side chain, was about equipotent with the corresponding 6-unsubstituted relative 2b. The reason for the failure of these apparently appropriately located labile protons to enhance beta-adrenoreceptor agonist activity is uncertain."}
{"id": "PMID:20504", "title": "Adrenergic agents. 8.1 Synthesis and beta-adrenergic agonist activity of some 3-tert-butylamino-2-(substituted phenyl)-1-propanols.", "content": "Replacement of the benzylic hydroxyl group of N-tert-butylnorepinephrine with a hydroxymethyl substituent affords a propanolamine homologue which retains a high degree of beta-adrenergic agonist activity. As modification of the meta substituent of catecholic ethanolamines, such as N-tert-butylnorepinephrine, often provides compounds that exert a more pronounced effect in relaxing tracheobronchial smooth muscle (beta2-adrenergic agonist) than in stimulating cardiac muscle (beta1-adrenergic response), a series of 3-tert-butylamino-2-(3-substituted 4-hydroxyphenyl)-1-propanols was prepared. The 3-meta substituents included HOCH2 (1b), H2NCONH (1c), MeSO2NH (1d), H (le), and NH2 (1f). These phenylpropanolamine derivatives were compared with their phenylethanolamine counterparts in in vitro tests that measure the ability of these compounds to relax spontaneously contracted guinea pig tracheal smooth muscle (a measure of potential bronchodilating activity) and to increase the rate of contraction of a spontaneously beating guinea pig right atrial preparation (an indicator of potential cardiac stimulating activity). In these tests all of the propanolamine derivatives included in the study were less potent than their ethanolamine relatives. In both series replacement of the catecholic m-hydroxyl group with the indicated substituents usually resulted in compounds with increased selectivity for tracheobronchial vs. cardiac muscle.", "contents": "Adrenergic agents. 8.1 Synthesis and beta-adrenergic agonist activity of some 3-tert-butylamino-2-(substituted phenyl)-1-propanols. Replacement of the benzylic hydroxyl group of N-tert-butylnorepinephrine with a hydroxymethyl substituent affords a propanolamine homologue which retains a high degree of beta-adrenergic agonist activity. As modification of the meta substituent of catecholic ethanolamines, such as N-tert-butylnorepinephrine, often provides compounds that exert a more pronounced effect in relaxing tracheobronchial smooth muscle (beta2-adrenergic agonist) than in stimulating cardiac muscle (beta1-adrenergic response), a series of 3-tert-butylamino-2-(3-substituted 4-hydroxyphenyl)-1-propanols was prepared. The 3-meta substituents included HOCH2 (1b), H2NCONH (1c), MeSO2NH (1d), H (le), and NH2 (1f). These phenylpropanolamine derivatives were compared with their phenylethanolamine counterparts in in vitro tests that measure the ability of these compounds to relax spontaneously contracted guinea pig tracheal smooth muscle (a measure of potential bronchodilating activity) and to increase the rate of contraction of a spontaneously beating guinea pig right atrial preparation (an indicator of potential cardiac stimulating activity). In these tests all of the propanolamine derivatives included in the study were less potent than their ethanolamine relatives. In both series replacement of the catecholic m-hydroxyl group with the indicated substituents usually resulted in compounds with increased selectivity for tracheobronchial vs. cardiac muscle."}
{"id": "PMID:20508", "title": "Ion permeability and strength of cell contacts: ion permeability and mechanical properties of cell contacts in small intestine epithelium.", "content": "The effects of several simple parameters (pH, concentration of bivalent cations, osmotic pressure, and temperature) on the ion permeability and mechanical properties of cell contacts have been investigated. It has been shown that the mechanical properties of a cell contact make it possible to describe it as a viscoelastic system. The main contribution to cell adhesion is made by the tight junction. Two populations of acidic centers have been identified on the cell membrane surface. One population interacts with bivalent cations to assure cell adhesion. The other population of weaker acidic centers regulating ion permeation is involved in the cell membrane's interaction of the repulsion type. An intimate correlation has been established between changes in passive transepithelial ion permeability and cell adhesion in response to changes in pH and in bivalent cation concentration. Such a correlation is possible if the tight junction is the principal contributor to the passive ion permeability and mechanical strength of the cell contacts.", "contents": "Ion permeability and strength of cell contacts: ion permeability and mechanical properties of cell contacts in small intestine epithelium. The effects of several simple parameters (pH, concentration of bivalent cations, osmotic pressure, and temperature) on the ion permeability and mechanical properties of cell contacts have been investigated. It has been shown that the mechanical properties of a cell contact make it possible to describe it as a viscoelastic system. The main contribution to cell adhesion is made by the tight junction. Two populations of acidic centers have been identified on the cell membrane surface. One population interacts with bivalent cations to assure cell adhesion. The other population of weaker acidic centers regulating ion permeation is involved in the cell membrane's interaction of the repulsion type. An intimate correlation has been established between changes in passive transepithelial ion permeability and cell adhesion in response to changes in pH and in bivalent cation concentration. Such a correlation is possible if the tight junction is the principal contributor to the passive ion permeability and mechanical strength of the cell contacts."}
{"id": "PMID:20513", "title": "Determination of specificity in natural cell-mediated cytotoxicity by natural antibodies.", "content": "Natural cell-mediated cytotoxicity (NCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) appeared to involve similar cytotoxic mechanisms; effector N-cells killed target cells with IgG antibodies attached to the Fc receptor determining the specificity of the reaction. In NCMC the wide range of specificities detected by natural antibodies provided an effector system capable of recognizing numerous antigens on cultured target cells. When several target cells were tested concurrently, an apparent nonselective cytotoxicity resulted. The specificity of individual reactions against each of the target cells could be demonstrated by selective inhibition with competitor cells. The inhibition of cytotoxicity by competition and the effect of proteases on the effector cell for NCMC, but not for ADCC, initially suggested an antibody on the surface of the natural cytotoxic effector cell. This suggestion was supported by the loss of activity with treatments that removed immunoglobulins on the effector cell and by the recovery of reactivity with incubation of the cells in normal human serum. Absorption of the reconstituting serum with target cells resulted in loss of activity against that target cell, substantiating the role of natural antibodies.", "contents": "Determination of specificity in natural cell-mediated cytotoxicity by natural antibodies. Natural cell-mediated cytotoxicity (NCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) appeared to involve similar cytotoxic mechanisms; effector N-cells killed target cells with IgG antibodies attached to the Fc receptor determining the specificity of the reaction. In NCMC the wide range of specificities detected by natural antibodies provided an effector system capable of recognizing numerous antigens on cultured target cells. When several target cells were tested concurrently, an apparent nonselective cytotoxicity resulted. The specificity of individual reactions against each of the target cells could be demonstrated by selective inhibition with competitor cells. The inhibition of cytotoxicity by competition and the effect of proteases on the effector cell for NCMC, but not for ADCC, initially suggested an antibody on the surface of the natural cytotoxic effector cell. This suggestion was supported by the loss of activity with treatments that removed immunoglobulins on the effector cell and by the recovery of reactivity with incubation of the cells in normal human serum. Absorption of the reconstituting serum with target cells resulted in loss of activity against that target cell, substantiating the role of natural antibodies."}
{"id": "PMID:20514", "title": "In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation.", "content": "In these experiments, we tested in various in vivo assays the immune responses of inbred C3H/HeN(MTV-) (C3H-) mice during carcinogenesis by chronic exposure to UV irradiation. Although the UV-treated mice were unable to reject syngeneic UV-induced tumor transplants, they rejected H-2-incompatible tumor allografts and H-2-compatible skin allografts. The primary hemagglutinin response to sheep red blood cells was normal in these mice, as were the induction of a local graft-versus-host reaction with lymphoid cells from UV-irradiated donors and the induction of an inflammatory response to dimethyl sulfoxide in the footpads of UV-treated mice. An early transient depression of two reactions in UV-irradiated mice occurred: delayed hypersensitivity to dinitrochlorobenzene measured by footpad swelling and the graft-versus-host reaction in UV-irradiated recipients measured by the use of the popliteal lymph node weight gain assay. Both of these reactions returned to a normal level before the development of primary tumors. We conclude that the inability of UV-irradiated mice to reject syngeneic and autochthonous UV-induced tumors was not due to a generalized immunosuppressive effect of chronic UV irradiation.", "contents": "In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation. In these experiments, we tested in various in vivo assays the immune responses of inbred C3H/HeN(MTV-) (C3H-) mice during carcinogenesis by chronic exposure to UV irradiation. Although the UV-treated mice were unable to reject syngeneic UV-induced tumor transplants, they rejected H-2-incompatible tumor allografts and H-2-compatible skin allografts. The primary hemagglutinin response to sheep red blood cells was normal in these mice, as were the induction of a local graft-versus-host reaction with lymphoid cells from UV-irradiated donors and the induction of an inflammatory response to dimethyl sulfoxide in the footpads of UV-treated mice. An early transient depression of two reactions in UV-irradiated mice occurred: delayed hypersensitivity to dinitrochlorobenzene measured by footpad swelling and the graft-versus-host reaction in UV-irradiated recipients measured by the use of the popliteal lymph node weight gain assay. Both of these reactions returned to a normal level before the development of primary tumors. We conclude that the inability of UV-irradiated mice to reject syngeneic and autochthonous UV-induced tumors was not due to a generalized immunosuppressive effect of chronic UV irradiation."}
{"id": "PMID:20515", "title": "Stimulation of cellular thymidine kinases by human cytomegalovirus.", "content": "Thymidine kinase (TK) activity in WI-38 and MRC-5 human fibroblasts was analyzed by discontinuous polyacrylamide gel electrophoresis (disc-PAGE) and discontinuous glycerol gradient electrophoresis (disc-GEP) after subculture or human cytomegalovirus (HCMV) infection. Two peaks of TK activity with different relative fraction-of-migration (R(f)) values were resolved by disc-PAGE or disc-GEP in extracts from log-phase and infected cells. Growing WI-38 cells expressed a slowly migrating (R(f) = 0.14 PAGE, R(f) = 0.4 GEP) peak of TK activity, which was partially inhibited by 1.0 mM dCTP, but which retained little activity at pH 4.5. Growing MRC cells also displayed a slowly migrating peak (R(f) = 0.10 PAGE) with similar properties. Both cell types expressed a faster-migrating TK activity (R(f) = 0.45 PAGE, R(f) = 0.7 GEP) in the growing and resting state that was strongly inhibited by 1 mM dCTP but retained 50% activity at pH 4.5. When either cell type was infected with HCMV, there was a rapid and high-level stimulation of the slowly migrating form of TK and a slight stimulation of the faster-migrating form. Two strains of HCMV (AD169 and Town) failed to produce an electrophoretically distinct virus TK in either cell type after infection. TK enzymes were partially purified by disc-GEP from extracts of log-phase WI-38 or AD169-infected WI-38 cells. Characterization of these enzymes with respect to phosphate donor specificity, pH optima, thermostability, and salt inhibition showed the HCMV-stimulated TKs to be of cellular origin.", "contents": "Stimulation of cellular thymidine kinases by human cytomegalovirus. Thymidine kinase (TK) activity in WI-38 and MRC-5 human fibroblasts was analyzed by discontinuous polyacrylamide gel electrophoresis (disc-PAGE) and discontinuous glycerol gradient electrophoresis (disc-GEP) after subculture or human cytomegalovirus (HCMV) infection. Two peaks of TK activity with different relative fraction-of-migration (R(f)) values were resolved by disc-PAGE or disc-GEP in extracts from log-phase and infected cells. Growing WI-38 cells expressed a slowly migrating (R(f) = 0.14 PAGE, R(f) = 0.4 GEP) peak of TK activity, which was partially inhibited by 1.0 mM dCTP, but which retained little activity at pH 4.5. Growing MRC cells also displayed a slowly migrating peak (R(f) = 0.10 PAGE) with similar properties. Both cell types expressed a faster-migrating TK activity (R(f) = 0.45 PAGE, R(f) = 0.7 GEP) in the growing and resting state that was strongly inhibited by 1 mM dCTP but retained 50% activity at pH 4.5. When either cell type was infected with HCMV, there was a rapid and high-level stimulation of the slowly migrating form of TK and a slight stimulation of the faster-migrating form. Two strains of HCMV (AD169 and Town) failed to produce an electrophoretically distinct virus TK in either cell type after infection. TK enzymes were partially purified by disc-GEP from extracts of log-phase WI-38 or AD169-infected WI-38 cells. Characterization of these enzymes with respect to phosphate donor specificity, pH optima, thermostability, and salt inhibition showed the HCMV-stimulated TKs to be of cellular origin."}
{"id": "PMID:20516", "title": "Properties of \"diplophage\": a lipid-containing bacteriophage.", "content": "We describe the purification and properties of Dp-1, a bacteriophage isolated from Diplococcus pneumoniae. The phage was sensitive to the organic solvents deoxycholate and Sarkosyl, and its infectivity was reduced by treatment with phospholipase C. Electron microscopy indicated the presence of a double-layered coat around the phage particles. Purified phage preparations contained lipid amounting to about 8.5% of the dry weight of the phage, and thin-layer chromatography resolved the lipids into four components. The phage had a buoyant density in CsCl of 1.47 g/cm3, and a sedimentation constant in 0.1 M NaCl of 313S. Analysis in acrylamide gel electrophoresis indicated the presence of three major proteins. Dp-1 DNA shows a density of 1.681 g/cm3. Neutralizing antisera against the phage have a low potency (K less than 120/min).", "contents": "Properties of \"diplophage\": a lipid-containing bacteriophage. We describe the purification and properties of Dp-1, a bacteriophage isolated from Diplococcus pneumoniae. The phage was sensitive to the organic solvents deoxycholate and Sarkosyl, and its infectivity was reduced by treatment with phospholipase C. Electron microscopy indicated the presence of a double-layered coat around the phage particles. Purified phage preparations contained lipid amounting to about 8.5% of the dry weight of the phage, and thin-layer chromatography resolved the lipids into four components. The phage had a buoyant density in CsCl of 1.47 g/cm3, and a sedimentation constant in 0.1 M NaCl of 313S. Analysis in acrylamide gel electrophoresis indicated the presence of three major proteins. Dp-1 DNA shows a density of 1.681 g/cm3. Neutralizing antisera against the phage have a low potency (K less than 120/min)."}
{"id": "PMID:20517", "title": "Specific binding sites for a parvovirus, minute virus of mice, on cultured mouse cells.", "content": "The early interactions between parvoviruses and host cells have not been extensively described previously. In this study we have characterized some aspects of viral binding to the cell surface and demonstrated the existence of specific cellular receptor sites for minute virus of mice (MVM) on two murine cell lines that are permissive for viral growth. The interaction had a pH optimum of 7.0 to 7.2, and both the rate and extent of the reactions were slightly affected by temperature. Mouse A-9 cells (L-cell derivative) had approximately 5 X 10(5) specific MVM binding sites per cell, and Friend erythroleukemia cells had 1.5 X 10(5) MVM sites per cell. In contrast, the nonpermissive mouse lymphoid cell line L1210 lacked specific viral receptors. Also, cloned lines of A-9 cells resistant to viral infection have been isolated. One of these lines lacked the \"specific\" virus attachment sites but exhibited low levels of nonsaturable virus binding. Based on these examples, infectivity is correlated with the presence of specific viral receptors on the cell surface.", "contents": "Specific binding sites for a parvovirus, minute virus of mice, on cultured mouse cells. The early interactions between parvoviruses and host cells have not been extensively described previously. In this study we have characterized some aspects of viral binding to the cell surface and demonstrated the existence of specific cellular receptor sites for minute virus of mice (MVM) on two murine cell lines that are permissive for viral growth. The interaction had a pH optimum of 7.0 to 7.2, and both the rate and extent of the reactions were slightly affected by temperature. Mouse A-9 cells (L-cell derivative) had approximately 5 X 10(5) specific MVM binding sites per cell, and Friend erythroleukemia cells had 1.5 X 10(5) MVM sites per cell. In contrast, the nonpermissive mouse lymphoid cell line L1210 lacked specific viral receptors. Also, cloned lines of A-9 cells resistant to viral infection have been isolated. One of these lines lacked the \"specific\" virus attachment sites but exhibited low levels of nonsaturable virus binding. Based on these examples, infectivity is correlated with the presence of specific viral receptors on the cell surface."}
{"id": "PMID:20518", "title": "Division of spermatic vessels in orchiopexy: radionuclide evidence of preservation of testicular circulation.", "content": "Satisfactory intrascrotal position of the testicles was achieved by dividing the spermatic vessels, leaving the vas deferens intact, in 3 patients with undescended testes. A postoperative scrotal scan provided objective means of evaluating the adequacy of testicular circulation. To determine the efficacy of various procedures for orchiopexy for undescended testes we suggest that postoperative evaluation include radionuclide imaging of the scrotum.", "contents": "Division of spermatic vessels in orchiopexy: radionuclide evidence of preservation of testicular circulation. Satisfactory intrascrotal position of the testicles was achieved by dividing the spermatic vessels, leaving the vas deferens intact, in 3 patients with undescended testes. A postoperative scrotal scan provided objective means of evaluating the adequacy of testicular circulation. To determine the efficacy of various procedures for orchiopexy for undescended testes we suggest that postoperative evaluation include radionuclide imaging of the scrotum."}
{"id": "PMID:20519", "title": "The medical management of angina pectoris.", "content": "The availability of excellent short-acting and long-acting drugs for the treatment of angina pectoris needs to be emphasized. Properly used in conjunction with other measures such as the treatment of hypertension and a graded exercise routine, they provide, for most patients with angina, a tested therapeutic program that is remarkably effective, well-tolerated, appropriate for long-term outpatient use, and quite inexpensive.", "contents": "The medical management of angina pectoris. The availability of excellent short-acting and long-acting drugs for the treatment of angina pectoris needs to be emphasized. Properly used in conjunction with other measures such as the treatment of hypertension and a graded exercise routine, they provide, for most patients with angina, a tested therapeutic program that is remarkably effective, well-tolerated, appropriate for long-term outpatient use, and quite inexpensive."}
{"id": "PMID:20520", "title": "Systemic vasculitis with coexistent large and small vessel involvement. A classification dilemma.", "content": "A patient with systemic vasculitis had the palpable purpuric lower extremity lesions of leukocytoclastic vasculitis and the renal aneurysms of polyarteritis nodosa, features thought to clearly separate these two syndromes. Questions are raised pertinent to the classification, diagnosis, treatment, and prognosis of systemic vasculitis.", "contents": "Systemic vasculitis with coexistent large and small vessel involvement. A classification dilemma. A patient with systemic vasculitis had the palpable purpuric lower extremity lesions of leukocytoclastic vasculitis and the renal aneurysms of polyarteritis nodosa, features thought to clearly separate these two syndromes. Questions are raised pertinent to the classification, diagnosis, treatment, and prognosis of systemic vasculitis."}
{"id": "PMID:20523", "title": "Antihypertensive effect of combined treatment with alpha- and beta-adrenergic blockers in the spontaneously hypertensive rat.", "content": "Using a continuous systolic monitor, effects of oral administration of three alpha-adrenergic blockers, i.e. phenoxybenzamine, phentolamine and a new quinazoline compound (2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6, 7-dimethoxy-quinazoline; E-643), on blood pressure and heart rate in normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). 1) An oral dose of 1 mg/kg phenoxybenzamine or E-643 almost completely reversed pressor response to adrenaline (2 microgram/kg i.v). Phentolamine was 3 to 5 times less effective than phenoxybenzamine and E-643. These alpha-blockers reduced pressor response to noradrenaline (2 microgram/kg i.v.) merely to one half at an oral dose of 100 mg/kg. 2) All these alpha-blockers did not reduce blood pressure but markedly increased heart rate in NWR. On the other hand, they reduced blood pressure of SHR without marked increase in heart rate. Although the alpha-blocking and cardiac stimulating effects of phenoxybenzamine lasted more than several days, its hypotensive effect in SHR disappeared within 24 hours. 3) An oral dose of 30 mg/kg propranolol did not reduce blood pressure in both NWR and SHR but slightly decreased heart rate. The combined treatment of these alpha-blockers with propranolol completely abolished the cardiac stimulating effect of the alpha-blockers and resulted in a definite reduction in blood pressure of NWR and potentiated the hypotensive effect of alpha-blockers in SHR.", "contents": "Antihypertensive effect of combined treatment with alpha- and beta-adrenergic blockers in the spontaneously hypertensive rat. Using a continuous systolic monitor, effects of oral administration of three alpha-adrenergic blockers, i.e. phenoxybenzamine, phentolamine and a new quinazoline compound (2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6, 7-dimethoxy-quinazoline; E-643), on blood pressure and heart rate in normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). 1) An oral dose of 1 mg/kg phenoxybenzamine or E-643 almost completely reversed pressor response to adrenaline (2 microgram/kg i.v). Phentolamine was 3 to 5 times less effective than phenoxybenzamine and E-643. These alpha-blockers reduced pressor response to noradrenaline (2 microgram/kg i.v.) merely to one half at an oral dose of 100 mg/kg. 2) All these alpha-blockers did not reduce blood pressure but markedly increased heart rate in NWR. On the other hand, they reduced blood pressure of SHR without marked increase in heart rate. Although the alpha-blocking and cardiac stimulating effects of phenoxybenzamine lasted more than several days, its hypotensive effect in SHR disappeared within 24 hours. 3) An oral dose of 30 mg/kg propranolol did not reduce blood pressure in both NWR and SHR but slightly decreased heart rate. The combined treatment of these alpha-blockers with propranolol completely abolished the cardiac stimulating effect of the alpha-blockers and resulted in a definite reduction in blood pressure of NWR and potentiated the hypotensive effect of alpha-blockers in SHR."}
{"id": "PMID:20527", "title": "Response of type B and E Botulinum toxins to purified sulfhydryl-dependent protease produced by Clostridium botulinum type F.", "content": "A sulfhydryl-dependent protease (SHP) was purified from a culture of Clostridium botulinum type F. The enzyme can activate type E progenitor toxin completely but type B progenitor toxin only partially. This may suggest that SHP by itself could completely activate the toxin of proteolytic C. botulinum types A and F in culture. The toxicity of type E progenitor toxin potentiated by the treatment with SHP persisted, whereas that of derivative toxin decreased rapidly by further incubation with SHP. This may indicate that only the progenitor toxin, the complex of the toxic and nontoxic components, activated by SHP withstands the subsequent exposure to the enzyme in cultures of proteolytic C. botulinum.", "contents": "Response of type B and E Botulinum toxins to purified sulfhydryl-dependent protease produced by Clostridium botulinum type F. A sulfhydryl-dependent protease (SHP) was purified from a culture of Clostridium botulinum type F. The enzyme can activate type E progenitor toxin completely but type B progenitor toxin only partially. This may suggest that SHP by itself could completely activate the toxin of proteolytic C. botulinum types A and F in culture. The toxicity of type E progenitor toxin potentiated by the treatment with SHP persisted, whereas that of derivative toxin decreased rapidly by further incubation with SHP. This may indicate that only the progenitor toxin, the complex of the toxic and nontoxic components, activated by SHP withstands the subsequent exposure to the enzyme in cultures of proteolytic C. botulinum."}
{"id": "PMID:20529", "title": "[Prevention and therapy of chronic cor pulmonale (author's transl)].", "content": "First prophylactic and therapeutic possibilities in cor pulmonale are shown on the basis of its pathogenesis. Our own results illustrate the effect of therapy of the underlying lung disease and of the concomitant respiratory insufficiency on the pulmonary arterial hypertension. The relationship between pulmonary artery pressure (PAp), arterial oxygen tension, forced expiratory volume of 1 second (FEV1%VC) and slow inspired viral capacity (VC) is analysed. In obstructive respiratory disorders the PAp rises when FEV1 falls below 40% of VC, in restrictive disorders when VC falls below 70% of predicted rate. 27 patients with chronic obstructive lung disease were treated with bronchodilator aerosols by intermittent positive pressure breathing (IPPB) during 2 years after a control period of 2 years: VC and FEV1 improved, the increase of total lung capacity and the deterioration of arterial blood gases came to a halt. The elevated PAp was always significantly reduced by oxygen therapy or IPPB or the combination of both. Finally, the rationale for avoiding physical stress in established cor pulmonale is illustrated: in healthy men PAp increases by less than 20% when cardiac output is doubled. In patients with cor pulmonale PAp rises to three times the initial value under the same conditions.", "contents": "[Prevention and therapy of chronic cor pulmonale (author's transl)]. First prophylactic and therapeutic possibilities in cor pulmonale are shown on the basis of its pathogenesis. Our own results illustrate the effect of therapy of the underlying lung disease and of the concomitant respiratory insufficiency on the pulmonary arterial hypertension. The relationship between pulmonary artery pressure (PAp), arterial oxygen tension, forced expiratory volume of 1 second (FEV1%VC) and slow inspired viral capacity (VC) is analysed. In obstructive respiratory disorders the PAp rises when FEV1 falls below 40% of VC, in restrictive disorders when VC falls below 70% of predicted rate. 27 patients with chronic obstructive lung disease were treated with bronchodilator aerosols by intermittent positive pressure breathing (IPPB) during 2 years after a control period of 2 years: VC and FEV1 improved, the increase of total lung capacity and the deterioration of arterial blood gases came to a halt. The elevated PAp was always significantly reduced by oxygen therapy or IPPB or the combination of both. Finally, the rationale for avoiding physical stress in established cor pulmonale is illustrated: in healthy men PAp increases by less than 20% when cardiac output is doubled. In patients with cor pulmonale PAp rises to three times the initial value under the same conditions."}
{"id": "PMID:20532", "title": "[Indices of human blood acid-base equilibrium and enzymatic activity in short-term antiorthostatic hypokinesia].", "content": "Before and after a 5 day head-down tilt of 4.5 degrees blood samples were withdrawn from different areas of the cardiovascular system of healthy male volunteers. Blood was sampled by means of selective catheterization. Parameters of acid-base equilibrium and activities of aminotransferases and alkaline phosphatase were measured. After immobilization the most significant changes were observed in the blood outflowing from the brain in which significant metabolic acidosis and increased activity of aspartate aminotransferase occurred. A slight increase in the activity of aspartate aminotransferase was also observed in the blood outflowing from the liver and kidneys. It is concluded that brain is the organ which is subjected to short-term simulated weightlessness in the highest degree.", "contents": "[Indices of human blood acid-base equilibrium and enzymatic activity in short-term antiorthostatic hypokinesia]. Before and after a 5 day head-down tilt of 4.5 degrees blood samples were withdrawn from different areas of the cardiovascular system of healthy male volunteers. Blood was sampled by means of selective catheterization. Parameters of acid-base equilibrium and activities of aminotransferases and alkaline phosphatase were measured. After immobilization the most significant changes were observed in the blood outflowing from the brain in which significant metabolic acidosis and increased activity of aspartate aminotransferase occurred. A slight increase in the activity of aspartate aminotransferase was also observed in the blood outflowing from the liver and kidneys. It is concluded that brain is the organ which is subjected to short-term simulated weightlessness in the highest degree."}
{"id": "PMID:20533", "title": "[Skeletal muscle lactate dehydrogenase isoenzymes in rats after space flight and in hypokinesia].", "content": "Carbohydrate metabolism of soleus (red) and plantaris (mixed) muscles of rats exposed to space flight and hypokinesia were studied on a comparative basis. The red and mixed muscles responded in a different way to the exposures, as followed from the changes of the isoenzymic spectrum of LDH. The soleus muscle showed the greatest changes in the LDH spectrum on the 15th hypokinetic day. The changes were similar to those found in the soleus muscle of flight rats. The plantaris muscle showed the most marked changes on the 60th hypokinetic day. Alterations in the LDH spectrum of the plantaris muscle were not found in flight or control rats. The findings indicate the major contribution of changes in carbohydrate metabolism to atrophic and dystrophic developments in skeletal muscles under functional load.", "contents": "[Skeletal muscle lactate dehydrogenase isoenzymes in rats after space flight and in hypokinesia]. Carbohydrate metabolism of soleus (red) and plantaris (mixed) muscles of rats exposed to space flight and hypokinesia were studied on a comparative basis. The red and mixed muscles responded in a different way to the exposures, as followed from the changes of the isoenzymic spectrum of LDH. The soleus muscle showed the greatest changes in the LDH spectrum on the 15th hypokinetic day. The changes were similar to those found in the soleus muscle of flight rats. The plantaris muscle showed the most marked changes on the 60th hypokinetic day. Alterations in the LDH spectrum of the plantaris muscle were not found in flight or control rats. The findings indicate the major contribution of changes in carbohydrate metabolism to atrophic and dystrophic developments in skeletal muscles under functional load."}
{"id": "PMID:20538", "title": "General principles of antimicrobial therapy.", "content": "In the initial therapy of life-threatening infections in which a bacterial cause is suspected, the emphasis should be on broad antibiotic coverage in contrast to definitive therapy, which is dependent on microbial isolation and, when indicated, in vitro susceptibility tests. In severe infections, antimicrobial agents should be given parenterally, at least initially. The need for optimal dosage is emphasized. This is particularly important when aminoglycosides are administered, for there is a tendency to use inadequate dosage because of concern for potential side effects with these agents. The problems leading to recurrence and persistence of fever during antimicrobial therapy include failure to diagnose and drain abscesses, superinfection, drug fever, and clinical or microbiologic errors. Combinations of antibiotics are indicated in severe infections in severe infections due to Pseudomonas aeruginosa, enterococcal group D streptococci, Klebsiella pneumoniae, and Cryptococcus neoformans. Laboratory aid for the selection of antimicrobial therapy can be of great value but need not always be done, because certain microorganisms have stable, predictable susceptibilities, for example, Streptococcus pneumoniae and Streptococcus pyogenes. Cautious conservatism is advocated with regard to the use of new antimicrobial agents.", "contents": "General principles of antimicrobial therapy. In the initial therapy of life-threatening infections in which a bacterial cause is suspected, the emphasis should be on broad antibiotic coverage in contrast to definitive therapy, which is dependent on microbial isolation and, when indicated, in vitro susceptibility tests. In severe infections, antimicrobial agents should be given parenterally, at least initially. The need for optimal dosage is emphasized. This is particularly important when aminoglycosides are administered, for there is a tendency to use inadequate dosage because of concern for potential side effects with these agents. The problems leading to recurrence and persistence of fever during antimicrobial therapy include failure to diagnose and drain abscesses, superinfection, drug fever, and clinical or microbiologic errors. Combinations of antibiotics are indicated in severe infections in severe infections due to Pseudomonas aeruginosa, enterococcal group D streptococci, Klebsiella pneumoniae, and Cryptococcus neoformans. Laboratory aid for the selection of antimicrobial therapy can be of great value but need not always be done, because certain microorganisms have stable, predictable susceptibilities, for example, Streptococcus pneumoniae and Streptococcus pyogenes. Cautious conservatism is advocated with regard to the use of new antimicrobial agents."}
{"id": "PMID:20550", "title": "Catecholamine-sensitive adenylate cyclase of human fat cell ghosts: a comparative study using different beta-adrenergic agents.", "content": "Some of the effects of beta-adrenergic agonists and antagonists on the adenylate cyclase system of human fat cell ghosts were studied. Isoproterenol, by causing about a fourfold increase of enzyme activity, was more potent than epinephrine and norepinephrine (about 2.5--3.0-fold stimulation). The beta2-adrenergic agonists salbutamol, terbutalin, and fenoterol were considerably less effective than the naturally occurring catecholamines. The stimulatory actions of isoproterenol and beta2-adrenergic agonists were competitively inhibited by the beta-blocking agent propranolol. Isoproterenol stimulation was also inhibited by the selective beta1-adrenergic antagonist practolol. This compound, however, was less potent than propranolol. The results are suggestive for an adenylate cyclase system in human fat cell ghosts coupled to beta1-adrenergic receptor sites. These receptors differ from the cardiac beta receptors with respect to practolol affinity.", "contents": "Catecholamine-sensitive adenylate cyclase of human fat cell ghosts: a comparative study using different beta-adrenergic agents. Some of the effects of beta-adrenergic agonists and antagonists on the adenylate cyclase system of human fat cell ghosts were studied. Isoproterenol, by causing about a fourfold increase of enzyme activity, was more potent than epinephrine and norepinephrine (about 2.5--3.0-fold stimulation). The beta2-adrenergic agonists salbutamol, terbutalin, and fenoterol were considerably less effective than the naturally occurring catecholamines. The stimulatory actions of isoproterenol and beta2-adrenergic agonists were competitively inhibited by the beta-blocking agent propranolol. Isoproterenol stimulation was also inhibited by the selective beta1-adrenergic antagonist practolol. This compound, however, was less potent than propranolol. The results are suggestive for an adenylate cyclase system in human fat cell ghosts coupled to beta1-adrenergic receptor sites. These receptors differ from the cardiac beta receptors with respect to practolol affinity."}
{"id": "PMID:20551", "title": "New evidence for growth hormone modulation by the alpha-adrenergic system in man.", "content": "The effect of BS 100-141, N-amidino 2-(2.6 dichlorophenyl) acetamide hydrochloride, a new drug with central alpha-adrenoceptor activity, on growth hormone (GH) secretion was investigated in 24 young, healthy volunteers. Six normal volunteers were treated with 1 mg and 8 with 2 mg BS 100-141; 8 of these 14 were treated with placebo, using single oral doses. Ten normal volunteers received single oral doses of 2 and 4 mg BS 100-141, 0.15 and 0.30 mg clonidine in a randomized, crossover study. GH secretion was significantly increased after 2 and 4 mg BS 100-141 and 0.30 mg clonidine. Prolactin and insulin plasma levels, glycerol, and blood sugar were not significantly influenced by BS 100-141. The results give new evidence for an alpha-adrenoceptor mechanism modulating GH secretion in normal young men.", "contents": "New evidence for growth hormone modulation by the alpha-adrenergic system in man. The effect of BS 100-141, N-amidino 2-(2.6 dichlorophenyl) acetamide hydrochloride, a new drug with central alpha-adrenoceptor activity, on growth hormone (GH) secretion was investigated in 24 young, healthy volunteers. Six normal volunteers were treated with 1 mg and 8 with 2 mg BS 100-141; 8 of these 14 were treated with placebo, using single oral doses. Ten normal volunteers received single oral doses of 2 and 4 mg BS 100-141, 0.15 and 0.30 mg clonidine in a randomized, crossover study. GH secretion was significantly increased after 2 and 4 mg BS 100-141 and 0.30 mg clonidine. Prolactin and insulin plasma levels, glycerol, and blood sugar were not significantly influenced by BS 100-141. The results give new evidence for an alpha-adrenoceptor mechanism modulating GH secretion in normal young men."}
{"id": "PMID:20557", "title": "Adverse reactions after smallpox vaccination.", "content": "Nine hundred and thirty-eight reports of adverse reactions of smallpox vaccination in Australia between 1960 and 1976 have been analysed according to the type of reaction, and the age and sex of vaccinee. In an estimated 5,000,000 vaccinations, the reaction rate was 188/million, and the death rate 1-5/million. Generalized vaccinia was the most common reaction. The more serious reactions--eczema vaccinatum, progressive vaccinia, and neurological and cardiac complications--accounted for 7-4% of the reports. A small number of rarely reported non-specific inflammatory reactions is also included. There was a marked difference in the number of reactions reported in females and males (the female-male ratio was 1-6:1), and this difference increased with age. Paradoxically, of eight reports of cardiac complications, seven concerned males. The administration of vaccinial immune globulin was usually followed by a rapid resolution of the adverse reactions.", "contents": "Adverse reactions after smallpox vaccination. Nine hundred and thirty-eight reports of adverse reactions of smallpox vaccination in Australia between 1960 and 1976 have been analysed according to the type of reaction, and the age and sex of vaccinee. In an estimated 5,000,000 vaccinations, the reaction rate was 188/million, and the death rate 1-5/million. Generalized vaccinia was the most common reaction. The more serious reactions--eczema vaccinatum, progressive vaccinia, and neurological and cardiac complications--accounted for 7-4% of the reports. A small number of rarely reported non-specific inflammatory reactions is also included. There was a marked difference in the number of reactions reported in females and males (the female-male ratio was 1-6:1), and this difference increased with age. Paradoxically, of eight reports of cardiac complications, seven concerned males. The administration of vaccinial immune globulin was usually followed by a rapid resolution of the adverse reactions."}
{"id": "PMID:20554", "title": "[Hydrogenase activity of the thermophilic hydrogen-oxidizing bacterium Pseudomonas thermophila].", "content": "The hydrogenase activity of the intact cells of a thermophilic hydrogen-oxidizing bacterium Pseudomonas thermophila K-2 was determined using methylene blue; it was several times higher than the rate of hydrogen uptake in the presence of oxygene and carbon dioxide. The activity of membrane-associated hydrogenase was assayed with the aid of phenazine methosulphate and 2,6-dichlorphenolindophenol as a cascade electron carrier. The enzyme is sufficiently stable in the air. The stability increases in the atmosphere of hydrogen. The membrane-bound enzyme was activated by Mn2+ ions. The pH-optimum of the enzyme activity in 0.1 M Tris-HCI buffer was 8,5-9,0. Natural electron acceptors tested, such as NAD, FMN, riboflavin, and cytochrome c, had no effect on the reaction rate. The enzyme is relatively thermostable: its activity was halved after heating at 78 degrees C for 10 min or at 80 degrees C for 8 min. Energy of activation was calculated. It was 14.5 kcal-mol-1 within the range of 23-40 degrees C and 10.3 kcal-mol-1 within the range of 40-60 degrees C.", "contents": "[Hydrogenase activity of the thermophilic hydrogen-oxidizing bacterium Pseudomonas thermophila]. The hydrogenase activity of the intact cells of a thermophilic hydrogen-oxidizing bacterium Pseudomonas thermophila K-2 was determined using methylene blue; it was several times higher than the rate of hydrogen uptake in the presence of oxygene and carbon dioxide. The activity of membrane-associated hydrogenase was assayed with the aid of phenazine methosulphate and 2,6-dichlorphenolindophenol as a cascade electron carrier. The enzyme is sufficiently stable in the air. The stability increases in the atmosphere of hydrogen. The membrane-bound enzyme was activated by Mn2+ ions. The pH-optimum of the enzyme activity in 0.1 M Tris-HCI buffer was 8,5-9,0. Natural electron acceptors tested, such as NAD, FMN, riboflavin, and cytochrome c, had no effect on the reaction rate. The enzyme is relatively thermostable: its activity was halved after heating at 78 degrees C for 10 min or at 80 degrees C for 8 min. Energy of activation was calculated. It was 14.5 kcal-mol-1 within the range of 23-40 degrees C and 10.3 kcal-mol-1 within the range of 40-60 degrees C."}
{"id": "PMID:20555", "title": "[Effect of p-chloromercuribenzoate on glutamine synthetase in the food yeast Candida tropicalis].", "content": "The effect of p-CMB on the activity of glutamine synthetase in the fodder yeast Candida tropicalis was studied in the synthetase reaction in Mg-, Mn-, and Co-activated systems and in the transferase reaction. The activity of glutamine synthetase was inhibited by pCMB, the degree of inhibition depending on the presence of bivalent cations of metals. Preliminay incubation of the enzyme with p-CMB stimulated the action of the latter, whereas metals increased the stability of the enzyme to pCMB. If the enzyme preparation was purified, it became more susceptible to the action of p-CMB. The transferase activity was also inhibited by p-CMB but to a less extent that the synthetase reaction.", "contents": "[Effect of p-chloromercuribenzoate on glutamine synthetase in the food yeast Candida tropicalis]. The effect of p-CMB on the activity of glutamine synthetase in the fodder yeast Candida tropicalis was studied in the synthetase reaction in Mg-, Mn-, and Co-activated systems and in the transferase reaction. The activity of glutamine synthetase was inhibited by pCMB, the degree of inhibition depending on the presence of bivalent cations of metals. Preliminay incubation of the enzyme with p-CMB stimulated the action of the latter, whereas metals increased the stability of the enzyme to pCMB. If the enzyme preparation was purified, it became more susceptible to the action of p-CMB. The transferase activity was also inhibited by p-CMB but to a less extent that the synthetase reaction."}
{"id": "PMID:20556", "title": "[Oospora lactis strain actively producing lipase].", "content": "Morphological, cultural and physiological properties of the fungus Oospora lactis producing lipase are described. The activity of lipase depends on the composition of a growth medium, pH, temperature, the duration of cultivation. Optimum conditions for lipase biosynthesis by the fungus have been found. The strain produces extracellular and endocellular lipases during submerged cultivation in the optimum growth medium at a high rate.", "contents": "[Oospora lactis strain actively producing lipase]. Morphological, cultural and physiological properties of the fungus Oospora lactis producing lipase are described. The activity of lipase depends on the composition of a growth medium, pH, temperature, the duration of cultivation. Optimum conditions for lipase biosynthesis by the fungus have been found. The strain produces extracellular and endocellular lipases during submerged cultivation in the optimum growth medium at a high rate."}
{"id": "PMID:20561", "title": "[Determination of acid-base parameters by means of programmable pocket calculators (author's transl)].", "content": "The possibility to calculate parameters of acid-base status derived by common laboratory devices without built-in computers is described. The calculation is carried out faster and more exactly than it is possible by nomograms, which is especially suitable when a great quantity of dates occurs. The number of programmable steps in some inexpensive pocket calculators is sufficient for this purpose; this type of \"microcomputers\" offers advantages of economy and small size so that calculations can be carried out immediately at the site where measurements are taken.", "contents": "[Determination of acid-base parameters by means of programmable pocket calculators (author's transl)]. The possibility to calculate parameters of acid-base status derived by common laboratory devices without built-in computers is described. The calculation is carried out faster and more exactly than it is possible by nomograms, which is especially suitable when a great quantity of dates occurs. The number of programmable steps in some inexpensive pocket calculators is sufficient for this purpose; this type of \"microcomputers\" offers advantages of economy and small size so that calculations can be carried out immediately at the site where measurements are taken."}
{"id": "PMID:20568", "title": "Purification and properties of alpha-amylase from chicken (Gallus gallus L.) pancreas.", "content": "Amylase from chicken pancreas was purified by an affinity method involving filtering a crude extract from pancreas through a Sepharose-wheat albumin column and eluting the retained enzyme with maltose. The purified amylase showed two active bands upon polyacrylamide electrophoresis in an alkaline buffer system and only one band in an acidic buffer system. The enzyme is a Ca2+-glycoprotein which behaves as a typical alpha-amylase. It consists of a single polypeptide chain with molecular weight 53,000 and contains 5.3 moles of reducing sugars per mole of protein. Optimal conditions of pH and temperature for the enzymic activity are 7.5 and 37 degrees C. The enzyme is irreversibly inactivated by removal of Ca2+ by exhaustive dialysis and is activated by the presence in the assay mixture of Cl-; other halides are less effective than Cl- in activating the enzyme.", "contents": "Purification and properties of alpha-amylase from chicken (Gallus gallus L.) pancreas. Amylase from chicken pancreas was purified by an affinity method involving filtering a crude extract from pancreas through a Sepharose-wheat albumin column and eluting the retained enzyme with maltose. The purified amylase showed two active bands upon polyacrylamide electrophoresis in an alkaline buffer system and only one band in an acidic buffer system. The enzyme is a Ca2+-glycoprotein which behaves as a typical alpha-amylase. It consists of a single polypeptide chain with molecular weight 53,000 and contains 5.3 moles of reducing sugars per mole of protein. Optimal conditions of pH and temperature for the enzymic activity are 7.5 and 37 degrees C. The enzyme is irreversibly inactivated by removal of Ca2+ by exhaustive dialysis and is activated by the presence in the assay mixture of Cl-; other halides are less effective than Cl- in activating the enzyme."}
{"id": "PMID:20569", "title": "Aminoacyl-tRNA synthetases from calf liver: optimized assay conditions and kinetic properties.", "content": "Kinetic studies have been performed on the \"family\" of aminoacyl synthetases from calf liver. All assays were based on the esterification of amino acids to tRNA. Optimized reaction conditions for each synthetase are reported. Most of the synthetases show hyperbolic kinetics with respect to both amino acid and tRNA concentration, however a few show sigmoidal kinetics with respect to one substrate. Arginine, methionine and proline synthetases show sigmoidal kinetics with respect to mixed tRNA solutions and have Hill coefficients of 1.30, 1.10 and 1.20 respectively. Alanine and isoleucine synthetases show sigmoidal kinetics with respect to amino acid concentration and have Hill coefficients of 1.21 and 1.40 respectively.", "contents": "Aminoacyl-tRNA synthetases from calf liver: optimized assay conditions and kinetic properties. Kinetic studies have been performed on the \"family\" of aminoacyl synthetases from calf liver. All assays were based on the esterification of amino acids to tRNA. Optimized reaction conditions for each synthetase are reported. Most of the synthetases show hyperbolic kinetics with respect to both amino acid and tRNA concentration, however a few show sigmoidal kinetics with respect to one substrate. Arginine, methionine and proline synthetases show sigmoidal kinetics with respect to mixed tRNA solutions and have Hill coefficients of 1.30, 1.10 and 1.20 respectively. Alanine and isoleucine synthetases show sigmoidal kinetics with respect to amino acid concentration and have Hill coefficients of 1.21 and 1.40 respectively."}
{"id": "PMID:20570", "title": "[Recent progress in research on the central regulation of growth hormone secretion (author's transl)].", "content": "The secretion of pituitary and peripheral hormones is regulated by a chain of reactions in the central nervous system. According to current knowledge this chain consists of the following links: external and internal stimuli leads to mesencephalon leads to limbic system leads to monoaminergic neurones leads to hypothalamic nuclei leads to liberines (releasing hormones) and inhibines (inhibiting horomones) leads to portal system leads to pituitary leads to peripheral endocrine gland. Long-loop and short-loop feedbacks regulate the activity of this relay system. The monoaminergic neurones secrete neurotransmitters, of which three are presently known: norepinephrine, dopamine, and serotonin. Most likely there also exists a cholinergic neurotransmitter. The secretion of neurotransmitters can be increased or reduced by specific drugs. On this basis, certain neuroendocrinopathies, such as deprivation dwarfism, hypothalamic acromegaly, and anorexia nervosa, may be treated speciafically. The pituitary secretion of growth hormone (GH) takes place mainly at night during deep sleep (slow-wave-sleep). This secretory pattern develops during the first year of life. It reaches its peak during puberty. At that time GH-spikes also occur during daytime. During adulthood GH secretion slowly diminishes again and at senescence it corresponds to early childhood.", "contents": "[Recent progress in research on the central regulation of growth hormone secretion (author's transl)]. The secretion of pituitary and peripheral hormones is regulated by a chain of reactions in the central nervous system. According to current knowledge this chain consists of the following links: external and internal stimuli leads to mesencephalon leads to limbic system leads to monoaminergic neurones leads to hypothalamic nuclei leads to liberines (releasing hormones) and inhibines (inhibiting horomones) leads to portal system leads to pituitary leads to peripheral endocrine gland. Long-loop and short-loop feedbacks regulate the activity of this relay system. The monoaminergic neurones secrete neurotransmitters, of which three are presently known: norepinephrine, dopamine, and serotonin. Most likely there also exists a cholinergic neurotransmitter. The secretion of neurotransmitters can be increased or reduced by specific drugs. On this basis, certain neuroendocrinopathies, such as deprivation dwarfism, hypothalamic acromegaly, and anorexia nervosa, may be treated speciafically. The pituitary secretion of growth hormone (GH) takes place mainly at night during deep sleep (slow-wave-sleep). This secretory pattern develops during the first year of life. It reaches its peak during puberty. At that time GH-spikes also occur during daytime. During adulthood GH secretion slowly diminishes again and at senescence it corresponds to early childhood."}
{"id": "PMID:20571", "title": "[Special problems of asthma bronchiale in childhood (author's transl)].", "content": "Asthma bronchiale is one of the most common chronic diseases in childhood. The hyperreactivity of the bronchial system, the stimulation of the cholinergic receptors and the blockade of the beta-adrenergic receptors in the bronchial mucosa play a predominant role in the pathogenesis. These proceedings cause bronchial smooth muscle contraction in the larger airways and mucosal edema and mucus hypersecretion in the smaller airways. The diagnosis may be made on the basis of the recurring signs: cough, wheezing, and labored breathing with prolonged expiration. Asthma may be treated by therapy directed at its cause and if necessary by bronchodilators, mucolytic agents and corticosteroids.", "contents": "[Special problems of asthma bronchiale in childhood (author's transl)]. Asthma bronchiale is one of the most common chronic diseases in childhood. The hyperreactivity of the bronchial system, the stimulation of the cholinergic receptors and the blockade of the beta-adrenergic receptors in the bronchial mucosa play a predominant role in the pathogenesis. These proceedings cause bronchial smooth muscle contraction in the larger airways and mucosal edema and mucus hypersecretion in the smaller airways. The diagnosis may be made on the basis of the recurring signs: cough, wheezing, and labored breathing with prolonged expiration. Asthma may be treated by therapy directed at its cause and if necessary by bronchodilators, mucolytic agents and corticosteroids."}
{"id": "PMID:20572", "title": "Comparative effects of antacids, cimetidine and enteric coating on the therapeutic response to oral enzymes in severe pancreatic insufficiency.", "content": "To provide a rational basis for pancreatic enzyme replacement therapy, we evaluated, in six patients with advanced pancreatic insufficiency, the effects of various treatment regimens on fecal fat and nitrogen balance and on duodenal recovery of ingested pancreatic enzymes after a solid test meal. The combination of cimetidine (an H2-receptor antagonist) and pancreatin, each given by mouth, produced significantly higher postprandial duodenal recoveries and concentrations of trypsin and lipase (P less than 0.05). Steatorrhea was reduced in all patients and abolished in four of the six. In the dosages used, neither enteric-coated enzymes nor supplemental neutralizing antacids were more effective than pancreatin alone in decreasing steatorrhea or improving duodenal enzyme delivery. Cimetidine may be a useful adjunct to oral pancreatic extract therapy in some patients with severe pancreatic insufficiency who fail to respond to pancreatic enzyme replacement alone.", "contents": "Comparative effects of antacids, cimetidine and enteric coating on the therapeutic response to oral enzymes in severe pancreatic insufficiency. To provide a rational basis for pancreatic enzyme replacement therapy, we evaluated, in six patients with advanced pancreatic insufficiency, the effects of various treatment regimens on fecal fat and nitrogen balance and on duodenal recovery of ingested pancreatic enzymes after a solid test meal. The combination of cimetidine (an H2-receptor antagonist) and pancreatin, each given by mouth, produced significantly higher postprandial duodenal recoveries and concentrations of trypsin and lipase (P less than 0.05). Steatorrhea was reduced in all patients and abolished in four of the six. In the dosages used, neither enteric-coated enzymes nor supplemental neutralizing antacids were more effective than pancreatin alone in decreasing steatorrhea or improving duodenal enzyme delivery. Cimetidine may be a useful adjunct to oral pancreatic extract therapy in some patients with severe pancreatic insufficiency who fail to respond to pancreatic enzyme replacement alone."}
{"id": "PMID:20575", "title": "Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy.", "content": "To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection.", "contents": "Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy. To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection."}
{"id": "PMID:20582", "title": "The facilitatory actions of aminopyridines and tetraethylammonium on neuromuscular transmission and muscle contractility in avian muscle.", "content": "The actions of 3,4-diaminopyridine, 4-aminopyridine and tetraethylammonium were studied on the chick biventer cervicis muscle preparation. All three compounds produced a greater augmentation of indirectly elicited twitches than of directly elicited twitches. The compounds did not restore transmission in OmMCa2+ solutions but rather produced contractures that were inhibited by acetylcholine receptor antagonists. The compounds restored twitch height in one-tenth normal Ca2+ solutions and induced spontaneous muscle twitching. The compounds reversed dantrolene-induced block of directly elicited twitches. Interactions between tetraethylammonium and 3,4-diaminopyridine were also studied. In indirectly stimulated preparations, the combined effects of the two compounds were more than additive at one concentration level only. In directly stimulated preparations, the effects of 3,4-diaminopyridine were greatly enhanced by tetraethylammonium pretreatment. 3,4-Diaminopyridine pretreatment produced less synergism than tetraethylammonium pretreatment. It is concluded that the actions of the aminopyridines and tetraethylammonium on transmitter release and muscle contractility are essentially similar. These actions are postulated to arise from an inhibitory action on potassium conductance and on an ability to release calcium from nerve and muscle membranes. On the basis of the interaction studies, it is suggested that the compounds possess different binding capacities for two different sites on the potassium conducting channel.", "contents": "The facilitatory actions of aminopyridines and tetraethylammonium on neuromuscular transmission and muscle contractility in avian muscle. The actions of 3,4-diaminopyridine, 4-aminopyridine and tetraethylammonium were studied on the chick biventer cervicis muscle preparation. All three compounds produced a greater augmentation of indirectly elicited twitches than of directly elicited twitches. The compounds did not restore transmission in OmMCa2+ solutions but rather produced contractures that were inhibited by acetylcholine receptor antagonists. The compounds restored twitch height in one-tenth normal Ca2+ solutions and induced spontaneous muscle twitching. The compounds reversed dantrolene-induced block of directly elicited twitches. Interactions between tetraethylammonium and 3,4-diaminopyridine were also studied. In indirectly stimulated preparations, the combined effects of the two compounds were more than additive at one concentration level only. In directly stimulated preparations, the effects of 3,4-diaminopyridine were greatly enhanced by tetraethylammonium pretreatment. 3,4-Diaminopyridine pretreatment produced less synergism than tetraethylammonium pretreatment. It is concluded that the actions of the aminopyridines and tetraethylammonium on transmitter release and muscle contractility are essentially similar. These actions are postulated to arise from an inhibitory action on potassium conductance and on an ability to release calcium from nerve and muscle membranes. On the basis of the interaction studies, it is suggested that the compounds possess different binding capacities for two different sites on the potassium conducting channel."}
{"id": "PMID:20583", "title": "Effects of db cAMP on tyrosine hydroxylase activity of ganglia and nerve endings.", "content": "Preincubation of intact superior cervical ganglia or nictitating membrane for 2 h with dibutyryl cyclic AMP (db cAMP) increased the hydroxylation of tyrosine. This effect was not blocked by the protein synthesis inhibitor, cycloheximide. The Km of tyrosine hydroxylase for the substrate, tyrosine, and for the cofactor, reduced pteridine, were decreased by db cAMP. There were no changes in the Vmax of the enzyme. The inhibitory potency of noradrenaline on the hydroxylation of tyrosine was also decreased. Thus an inductive effect may be ruled out. The activation of the enzyme was only observed when the tissues were preincubated with the db cAMP and not when the cyclic nucleotide was added to the isolated enzyme. Preincubation of cervical ganglia for 4 h with db cAMP increased activity of decarboxylase and monoamine oxidase in tissue homogenates without changing the tyrosine hydroxylase activity.", "contents": "Effects of db cAMP on tyrosine hydroxylase activity of ganglia and nerve endings. Preincubation of intact superior cervical ganglia or nictitating membrane for 2 h with dibutyryl cyclic AMP (db cAMP) increased the hydroxylation of tyrosine. This effect was not blocked by the protein synthesis inhibitor, cycloheximide. The Km of tyrosine hydroxylase for the substrate, tyrosine, and for the cofactor, reduced pteridine, were decreased by db cAMP. There were no changes in the Vmax of the enzyme. The inhibitory potency of noradrenaline on the hydroxylation of tyrosine was also decreased. Thus an inductive effect may be ruled out. The activation of the enzyme was only observed when the tissues were preincubated with the db cAMP and not when the cyclic nucleotide was added to the isolated enzyme. Preincubation of cervical ganglia for 4 h with db cAMP increased activity of decarboxylase and monoamine oxidase in tissue homogenates without changing the tyrosine hydroxylase activity."}
{"id": "PMID:20584", "title": "Naloxone-precipitated withdrawal reveals sensitization to neurotransmitters in morphine tolerant/dependent rats.", "content": "Morphine tolerant/dependent rats were tested for their sensitivity to putative neurotransmitters or other receptor agonists injected intracerebroventricularly (i.c.v.) during naloxone-precipitated withdrawal. Dopamine, apomorphine, clonidine and serotonin were found to reinitiate withdrawal jumping behaviour when injected 30 min after naloxone. Dopamine and apomorphine also reinitiated jumping, but of a lesser intensity, when injected 3 h after naloxone-precipitated withdrawal. I.c.v. injection of acetylcholine or prostaglandin E1 failed to reinitiate withdrawal jumping. In addition, all the above substances failed to induce jumping behaviour in naive rats or in morphine tolerant/dependent rats before naloxone-precipitated withdrawal. Morphine tolerance and dependence therefore appears to be associated with changes in the sensitivity of the CNS to putative neurotransmitter substances. These changes are best demonstrated during the sudden termination of opiate action that is caused by administration of naloxone.", "contents": "Naloxone-precipitated withdrawal reveals sensitization to neurotransmitters in morphine tolerant/dependent rats. Morphine tolerant/dependent rats were tested for their sensitivity to putative neurotransmitters or other receptor agonists injected intracerebroventricularly (i.c.v.) during naloxone-precipitated withdrawal. Dopamine, apomorphine, clonidine and serotonin were found to reinitiate withdrawal jumping behaviour when injected 30 min after naloxone. Dopamine and apomorphine also reinitiated jumping, but of a lesser intensity, when injected 3 h after naloxone-precipitated withdrawal. I.c.v. injection of acetylcholine or prostaglandin E1 failed to reinitiate withdrawal jumping. In addition, all the above substances failed to induce jumping behaviour in naive rats or in morphine tolerant/dependent rats before naloxone-precipitated withdrawal. Morphine tolerance and dependence therefore appears to be associated with changes in the sensitivity of the CNS to putative neurotransmitter substances. These changes are best demonstrated during the sudden termination of opiate action that is caused by administration of naloxone."}
{"id": "PMID:20586", "title": "Enhanced sympathetic activity in young spontaneously hypertensive rats is not the trigger mechanism for genetic hypertension.", "content": "In young, spontaneously hypertensive rats (SHR), a preganglionic, nerve-dependent, elevation of choline acetyltransferase (ChAc) and tyrosine hydroxylase (TH) activities was found in celiac ganglia as compared with those in young, normotensive Kyoto Wistar rats, that was not present in superior cervical ganglia, stellate ganglia and adrenal glands. The rise in both enzyme activities in the celiac ganglion disappeared in adult SHR. An elevation of plasma norepinephrine and dopamine beta-hydroxylase levels found in prehypertensive SHR, a probable indication of peripheral sympathetic activation, disappeared after the bilateral removal of the celiac ganglion. However, ganglionectomy did not change the subsequent development of hypertension. These results indicate that the faster maturation of the celiac ganglion and the end organs it innervates in yount SHR are causally related to the activation of the peripheral sympathetic nervous system. The peripheral sympathetic activation in young SHR is regarded as a warning sign but this does not trigger the development of hypertension.", "contents": "Enhanced sympathetic activity in young spontaneously hypertensive rats is not the trigger mechanism for genetic hypertension. In young, spontaneously hypertensive rats (SHR), a preganglionic, nerve-dependent, elevation of choline acetyltransferase (ChAc) and tyrosine hydroxylase (TH) activities was found in celiac ganglia as compared with those in young, normotensive Kyoto Wistar rats, that was not present in superior cervical ganglia, stellate ganglia and adrenal glands. The rise in both enzyme activities in the celiac ganglion disappeared in adult SHR. An elevation of plasma norepinephrine and dopamine beta-hydroxylase levels found in prehypertensive SHR, a probable indication of peripheral sympathetic activation, disappeared after the bilateral removal of the celiac ganglion. However, ganglionectomy did not change the subsequent development of hypertension. These results indicate that the faster maturation of the celiac ganglion and the end organs it innervates in yount SHR are causally related to the activation of the peripheral sympathetic nervous system. The peripheral sympathetic activation in young SHR is regarded as a warning sign but this does not trigger the development of hypertension."}
{"id": "PMID:20592", "title": "[A case of polyarteritis nodosa associated with pulmonary hypertension].", "content": "A case of polyarteritis nodosa marked by concomitant systemic and pulmonary hypertension is presented. The part played by pulmonary hypertension in this disease is briefly discussed in the light of the necropsy findings and the literature.", "contents": "[A case of polyarteritis nodosa associated with pulmonary hypertension]. A case of polyarteritis nodosa marked by concomitant systemic and pulmonary hypertension is presented. The part played by pulmonary hypertension in this disease is briefly discussed in the light of the necropsy findings and the literature."}
{"id": "PMID:20594", "title": "[Effect of age of mouse recipients on the functional activity of transplanted hematopoietic and lymphoid cells].", "content": "When transplanting the bone marrow cells from adult C57BL mice to the lethally irradiated (CBA X C57BL) F1 hybrids of different age, the decrease of the colony forming activity of the stem haemopoietic cells was observed in the spleen of the older recipients, as compared with the 3 months old ones. The joint transplantation of the bone marrow and thymus cells resulted in both the cases in the stimulation of the growth of colonies. The number of endogenous colonies of haemopoietic cells arising in the spleen of animals following the sublethal irradiation was greater in younger hybrids. After the induction of the \"transplant versus host\" reaction by the lymph node or spleen cells from the CBA mice, the relative weight of spleen and regional lymph node, respectively, in the older recipients exceeded those in the younger ones.", "contents": "[Effect of age of mouse recipients on the functional activity of transplanted hematopoietic and lymphoid cells]. When transplanting the bone marrow cells from adult C57BL mice to the lethally irradiated (CBA X C57BL) F1 hybrids of different age, the decrease of the colony forming activity of the stem haemopoietic cells was observed in the spleen of the older recipients, as compared with the 3 months old ones. The joint transplantation of the bone marrow and thymus cells resulted in both the cases in the stimulation of the growth of colonies. The number of endogenous colonies of haemopoietic cells arising in the spleen of animals following the sublethal irradiation was greater in younger hybrids. After the induction of the \"transplant versus host\" reaction by the lymph node or spleen cells from the CBA mice, the relative weight of spleen and regional lymph node, respectively, in the older recipients exceeded those in the younger ones."}
{"id": "PMID:20595", "title": "Familial tyrosinaemia with eye and skin lesions. Presentation of two cases.", "content": "Two cases of tyrosinaemia with eye and skin lesions typical of the Richner-Hanhart syndrome are described. The patients are a 29- and 26-year-old brother and sister. They do not show neurological abnormalities or mental retardation. Parents are not consanguineous and family history is negative for similar conditions. The diagnosis of type II tyrosinaemia was based upon an increase of blood tyrosine (14-16mg/100 ml), tyrosinuria and absence of liver and kidney abnormalities. The treatment with a low tyrosine phenylalanine diet has resulted in a disappearence of the ocular manifestations while the cutaneous lesions are much improved.", "contents": "Familial tyrosinaemia with eye and skin lesions. Presentation of two cases. Two cases of tyrosinaemia with eye and skin lesions typical of the Richner-Hanhart syndrome are described. The patients are a 29- and 26-year-old brother and sister. They do not show neurological abnormalities or mental retardation. Parents are not consanguineous and family history is negative for similar conditions. The diagnosis of type II tyrosinaemia was based upon an increase of blood tyrosine (14-16mg/100 ml), tyrosinuria and absence of liver and kidney abnormalities. The treatment with a low tyrosine phenylalanine diet has resulted in a disappearence of the ocular manifestations while the cutaneous lesions are much improved."}
{"id": "PMID:20596", "title": "Prenatal diagnosis of metachromatic leukodystrophy by electrophoretic and immunologic techniques.", "content": "Electrophoretic examination of extracts of cultured amniotic fluid cells from a pregnancy at risk for metachromatic leukodystrophy (MLD) showed absence of arylsulfatase A (AS-A) activity. Immunodiffusion with anti-human AS-A immune serum failed to show enzymatically active arcs of immune precipitate. Electrophoretic studies and quantitative assay of extracts of organs from the aborted fetus confirmed the diagnosis of MLD. Electrophoresis of amniotic fluid from this and one additional fetus with MLD showed an arylsulfatase pattern qualitatively and quantitatively indistinguishable from normal. In both normal and MLD fluids, the AS-A band was replaced by a band with lower anodal mobility. Only the anodal band of normal amniotic fluid, however, reacted with the anti-AS-A immune serum in immunoelectrophoresis. Assay of amniotic fluic with p-nitrocatechol sulfate (PNCS) as a substrate showed marked deficiency of \"AS-A\" activity in the fluids from the two MLD pregnancies. An optimal procedure for prenatal detection of MLD should include electrophoresis of extracts of cultured amniotic fluid cells with visual demonstration of absence of AS-A activity. Immunologic techniques applied to cell-free amniotic fluid may be of help in the rapid identification of the fetal genotypes.", "contents": "Prenatal diagnosis of metachromatic leukodystrophy by electrophoretic and immunologic techniques. Electrophoretic examination of extracts of cultured amniotic fluid cells from a pregnancy at risk for metachromatic leukodystrophy (MLD) showed absence of arylsulfatase A (AS-A) activity. Immunodiffusion with anti-human AS-A immune serum failed to show enzymatically active arcs of immune precipitate. Electrophoretic studies and quantitative assay of extracts of organs from the aborted fetus confirmed the diagnosis of MLD. Electrophoresis of amniotic fluid from this and one additional fetus with MLD showed an arylsulfatase pattern qualitatively and quantitatively indistinguishable from normal. In both normal and MLD fluids, the AS-A band was replaced by a band with lower anodal mobility. Only the anodal band of normal amniotic fluid, however, reacted with the anti-AS-A immune serum in immunoelectrophoresis. Assay of amniotic fluic with p-nitrocatechol sulfate (PNCS) as a substrate showed marked deficiency of \"AS-A\" activity in the fluids from the two MLD pregnancies. An optimal procedure for prenatal detection of MLD should include electrophoresis of extracts of cultured amniotic fluid cells with visual demonstration of absence of AS-A activity. Immunologic techniques applied to cell-free amniotic fluid may be of help in the rapid identification of the fetal genotypes."}
{"id": "PMID:20597", "title": "A patient with severe neurologic symptoms and acetoacetyl-CoA thiolase deficiency.", "content": "A detailed kinetic characterization of the cytosolic acetoacetyl-CoA thiolase in liver, subcutaneous adipose tissue, and cultured fibroblasts of a patient with severe neurologic symptoms showed this enzyme to be much more sensitive to inhibition by CoA than that enzyme of normal human liver. The activity of the cytosolic acetoacetyl-CoA of this patient (14.0 mu mol-min-1-g (w/w) was in the lower range of normal (48.7 +/- 20.4 mu mol-min-1 g (w/w), n=6), but the ratio of the mitochondrial thiolase over the cytosoli thiolase was significantly increased (14.9 versus 4.54 +/- 2.92, n =6). The increased inhibition of the cytosolic acetoacetyl-CoA thiolase by CoA shows up as a 2-fold increase of the apparent Km for acetoacetyl-CoA at physiologic concentrations of CoA (64 micrometer for the enzyme of the patient verus 35 micrometer for the normal enzymes), resulting in a decreased utilization of the substrate. Aberrant kinetic behaviour of the mitochondrial thiolases of the patient has also been observed, but this has not been analysed further. Morphologic studies of the liver showed greatly increased deposition of glycogen and the occurrence of lipofuschin-like granules.", "contents": "A patient with severe neurologic symptoms and acetoacetyl-CoA thiolase deficiency. A detailed kinetic characterization of the cytosolic acetoacetyl-CoA thiolase in liver, subcutaneous adipose tissue, and cultured fibroblasts of a patient with severe neurologic symptoms showed this enzyme to be much more sensitive to inhibition by CoA than that enzyme of normal human liver. The activity of the cytosolic acetoacetyl-CoA of this patient (14.0 mu mol-min-1-g (w/w) was in the lower range of normal (48.7 +/- 20.4 mu mol-min-1 g (w/w), n=6), but the ratio of the mitochondrial thiolase over the cytosoli thiolase was significantly increased (14.9 versus 4.54 +/- 2.92, n =6). The increased inhibition of the cytosolic acetoacetyl-CoA thiolase by CoA shows up as a 2-fold increase of the apparent Km for acetoacetyl-CoA at physiologic concentrations of CoA (64 micrometer for the enzyme of the patient verus 35 micrometer for the normal enzymes), resulting in a decreased utilization of the substrate. Aberrant kinetic behaviour of the mitochondrial thiolases of the patient has also been observed, but this has not been analysed further. Morphologic studies of the liver showed greatly increased deposition of glycogen and the occurrence of lipofuschin-like granules."}
{"id": "PMID:20600", "title": "An emerging zoonosis in Scandinavia -- nephropathia epidemica.", "content": "The paper reviews as zoonosis the disease called Nephropathia epidemica in north European countries. The etiology is as yet unsolved but a viral one is highly suspected with small rodents (voles and mice) as the source of infection. Based on the epidemiological peculiarities of the disease, the ecology of the agent and hypothetical ways of transmission of infection from small rodents to man are discussed.", "contents": "An emerging zoonosis in Scandinavia -- nephropathia epidemica. The paper reviews as zoonosis the disease called Nephropathia epidemica in north European countries. The etiology is as yet unsolved but a viral one is highly suspected with small rodents (voles and mice) as the source of infection. Based on the epidemiological peculiarities of the disease, the ecology of the agent and hypothetical ways of transmission of infection from small rodents to man are discussed."}
{"id": "PMID:20602", "title": "[The renin-angiotensin-aldosterone system in hypertensive subjects. III- The use of beta-blockers in reno-vascular hypertension (author's transl)].", "content": "Six patients with permanent hypertension with renal artery stenosis were treated by conservative reparative surgery appart from one of them (unilateral nephrectomy) and were all seen again at the 8th month at the earliest in the absence of any anti-hypertensive therapy. Study of the renin-angiotensin system carried out on a normal sodium diet, after stopping all anti-hypertensive treatment for at least 15 days, was combined with the anti-hypertensive response under the influence of a beta-blocker. There were two types of response pre-operatively: firstly, with beta-blockers alone a normal blood pressure which remained normal postoperatively; the second group of patients remained hypertensive, requiring the addition of diuretics, and remained hypertensive after surgery. This response, although non-specific, would appear to represent an important element in assessing the curability of reno-vascular hypertension.", "contents": "[The renin-angiotensin-aldosterone system in hypertensive subjects. III- The use of beta-blockers in reno-vascular hypertension (author's transl)]. Six patients with permanent hypertension with renal artery stenosis were treated by conservative reparative surgery appart from one of them (unilateral nephrectomy) and were all seen again at the 8th month at the earliest in the absence of any anti-hypertensive therapy. Study of the renin-angiotensin system carried out on a normal sodium diet, after stopping all anti-hypertensive treatment for at least 15 days, was combined with the anti-hypertensive response under the influence of a beta-blocker. There were two types of response pre-operatively: firstly, with beta-blockers alone a normal blood pressure which remained normal postoperatively; the second group of patients remained hypertensive, requiring the addition of diuretics, and remained hypertensive after surgery. This response, although non-specific, would appear to represent an important element in assessing the curability of reno-vascular hypertension."}
{"id": "PMID:20603", "title": "Enzymatic synthesis of Q nucleoside containing mannose in the anticodon of tRNA: isolation of a novel mannosyltransferase from a cell-free extract of rat liver.", "content": "The Q nucleosides isolated from rabbit liver tRNA are known to have sugars (mannose or galactose) linked to their cyclopentene diol moiety. A Q nucleoside containing mannose (manQ) was synthesized by a cell-free system from rat liver, using purified E. coli tRNAAsp as an acceptor and GDP-mannose as a donor molecule. The novel mannosyltransferase catalyzing this reaction was purified from a particulate-free soluble enzyme fraction and found to be strictly specific for tRNAAsp. These results, together with the anomeric configuration of mannose in Q nucleoside, indicate that no lipid intermediate is involved in the biosynthesis of Q nucleoside.", "contents": "Enzymatic synthesis of Q nucleoside containing mannose in the anticodon of tRNA: isolation of a novel mannosyltransferase from a cell-free extract of rat liver. The Q nucleosides isolated from rabbit liver tRNA are known to have sugars (mannose or galactose) linked to their cyclopentene diol moiety. A Q nucleoside containing mannose (manQ) was synthesized by a cell-free system from rat liver, using purified E. coli tRNAAsp as an acceptor and GDP-mannose as a donor molecule. The novel mannosyltransferase catalyzing this reaction was purified from a particulate-free soluble enzyme fraction and found to be strictly specific for tRNAAsp. These results, together with the anomeric configuration of mannose in Q nucleoside, indicate that no lipid intermediate is involved in the biosynthesis of Q nucleoside."}
{"id": "PMID:20604", "title": "The role of the AT pairs in the acid denaturation of DNA.", "content": "It has been determined previously that the protonation of the GC pairs induces a DNA conformation change which leads to a \"metastable\" structure. The role of the AT pairs, however, is no well known because the protonation does not modify their spectral properties. By means of an indirect method based on the binding of proflavine, it has been determined that the AT pairs are protonated before the acid-induced denaturation and that they seem to be unable to assume a conformation change when protonated. These results would indicate that the protonated AT pairs may be responsible for the induction of the acid denaturation and not the GC pairs as it was thought previously.", "contents": "The role of the AT pairs in the acid denaturation of DNA. It has been determined previously that the protonation of the GC pairs induces a DNA conformation change which leads to a \"metastable\" structure. The role of the AT pairs, however, is no well known because the protonation does not modify their spectral properties. By means of an indirect method based on the binding of proflavine, it has been determined that the AT pairs are protonated before the acid-induced denaturation and that they seem to be unable to assume a conformation change when protonated. These results would indicate that the protonated AT pairs may be responsible for the induction of the acid denaturation and not the GC pairs as it was thought previously."}
{"id": "PMID:20608", "title": "Participation of 5-hydroxytryptamine in anticonvulsive action of benzodiazepines.", "content": "The influence of several compounds activating or producing hypofunction of the serotonergic system was studied on the convulsive threshold and anticonvulsive action of benzodiazepines (chlordiazepoxide, diazepam, oxazepam, nitrazepam) in the pentylenetetrazol test. No changes in the convulsive threshold either for clonic, nor for tonic phase were found. However, the anticonvulsive action of benzodiazepines was enhanced by 5-hydroxytryptophan, 5-methoxytryptamine (given together with pargyline), or fenfluramine. p-Chlorophenylalanine and methergoline did not affect, but cyproheptadine enhanced the anticonvulsive action of most of benzodiazepines tested.", "contents": "Participation of 5-hydroxytryptamine in anticonvulsive action of benzodiazepines. The influence of several compounds activating or producing hypofunction of the serotonergic system was studied on the convulsive threshold and anticonvulsive action of benzodiazepines (chlordiazepoxide, diazepam, oxazepam, nitrazepam) in the pentylenetetrazol test. No changes in the convulsive threshold either for clonic, nor for tonic phase were found. However, the anticonvulsive action of benzodiazepines was enhanced by 5-hydroxytryptophan, 5-methoxytryptamine (given together with pargyline), or fenfluramine. p-Chlorophenylalanine and methergoline did not affect, but cyproheptadine enhanced the anticonvulsive action of most of benzodiazepines tested."}
{"id": "PMID:20609", "title": "The effect of alpha-adrenolytics on central action of agonists and antagonists of dopaminergic system.", "content": "alpha-Adrenoceptor blocking agents: phenoxybenzamine, phentolamine and aceperone, potentiated and prolonged amphetamine and apomorphine stereotypy in the rat, but inhibited the amphetamine hypermotility. The hypermotility produced by apomorphine was antagonized only by aceperone. Cataleptogenic action of haloperidol and fluphenazine was inhibited by the alpha-adrenoceptor blocking agents. Phenoxybenzamine and phentolamine, and to a smaller degree aceperone, inhibited the depletion of dopamine following pretreatment of rats with alpha-methyltyrosine. The results indicate that the blockade of central alpha-adrenergic receptors changes the reactivity of dopaminergic system on the action of its agonists and antagonists.", "contents": "The effect of alpha-adrenolytics on central action of agonists and antagonists of dopaminergic system. alpha-Adrenoceptor blocking agents: phenoxybenzamine, phentolamine and aceperone, potentiated and prolonged amphetamine and apomorphine stereotypy in the rat, but inhibited the amphetamine hypermotility. The hypermotility produced by apomorphine was antagonized only by aceperone. Cataleptogenic action of haloperidol and fluphenazine was inhibited by the alpha-adrenoceptor blocking agents. Phenoxybenzamine and phentolamine, and to a smaller degree aceperone, inhibited the depletion of dopamine following pretreatment of rats with alpha-methyltyrosine. The results indicate that the blockade of central alpha-adrenergic receptors changes the reactivity of dopaminergic system on the action of its agonists and antagonists."}
{"id": "PMID:20610", "title": "The effect of beta-adrenergic receptor blocking agents on hypertensive action of noradrenaline injected into the lateral ventricle of rat brain.", "content": "Noradrenaline (NA), 100 microgram intraventricularly (ivtr), produces an evident hypertension, lasting for up to 15 min. A previous ivtr administration of propranolol (100 and 500 microgram), alprenolol (100 microgram), sotalol (100 microgram), (-)INPEA (100 microgram), (+)INPEA (100 microgram), Ko 1366 (100 and 200 microgram), or practolol (20 microgram) abolishes the hypertensive action of NA. The results indicate that the central nervous system of the rat contains structures similar to the peripheral beta-adrenoceptor, and that they are involved in the central regulation of circulation.", "contents": "The effect of beta-adrenergic receptor blocking agents on hypertensive action of noradrenaline injected into the lateral ventricle of rat brain. Noradrenaline (NA), 100 microgram intraventricularly (ivtr), produces an evident hypertension, lasting for up to 15 min. A previous ivtr administration of propranolol (100 and 500 microgram), alprenolol (100 microgram), sotalol (100 microgram), (-)INPEA (100 microgram), (+)INPEA (100 microgram), Ko 1366 (100 and 200 microgram), or practolol (20 microgram) abolishes the hypertensive action of NA. The results indicate that the central nervous system of the rat contains structures similar to the peripheral beta-adrenoceptor, and that they are involved in the central regulation of circulation."}
{"id": "PMID:20611", "title": "Kinetics of drug decomposition. Part 45. Logk--pH profile for rolitetracycline degradation.", "content": "UV spectrophotometry and fluorometry were applied for an examination of rolitetracycline (RT) degradation at pH's ranged from ca 0-8 to 13-0. It was demonstrated that these methods enable to follow the rate of degradation of tetracycline formed in the course of RT hydrolysis. However, they do not allow to monitor the hydrolysis of RT to tetracycline. Application of the so-called \"subtraction technique\" permits to calculate the rate constants for the total, reversible epimerization reaction and for the subsequent degradation of the resultant products. A rate equation derived for RT degradation in an alkaline medium beginning at pH 10-5 contains a term second-order in the hydroxide ion. Such a relationship was not yet observed in the course of an antibiotic degradation.", "contents": "Kinetics of drug decomposition. Part 45. Logk--pH profile for rolitetracycline degradation. UV spectrophotometry and fluorometry were applied for an examination of rolitetracycline (RT) degradation at pH's ranged from ca 0-8 to 13-0. It was demonstrated that these methods enable to follow the rate of degradation of tetracycline formed in the course of RT hydrolysis. However, they do not allow to monitor the hydrolysis of RT to tetracycline. Application of the so-called \"subtraction technique\" permits to calculate the rate constants for the total, reversible epimerization reaction and for the subsequent degradation of the resultant products. A rate equation derived for RT degradation in an alkaline medium beginning at pH 10-5 contains a term second-order in the hydroxide ion. Such a relationship was not yet observed in the course of an antibiotic degradation."}
{"id": "PMID:20612", "title": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part III. The use of Hammett equation for kinetic investigation of 2-sulfanilamidopyrimidine derivatives autoxidation.", "content": "General first-order rate constants for autoxidation of sulfadiazine, sulfamerazine, sulfadimidine, sulfaperine and sulfamethoxydiazine in the air oxygen atmosphere, in solutions of pH 4-7, at 403, 411 and 418 K were determined from the absorbance measurements in 0-1 mole/dm3 HCl at 243 or 333 nm, using the so-called \"subtraction technique\". The thermodynamic parameters of this reaction were determined (deltaHa, deltaH not equal to, deltaS not equal to, deltaG not equal to and logA). The effect of the substituents in positions 4, 5 and 6 of the pyrimidine ring on the rate of autoxidation was interpreted in terms of the Hammett equation.", "contents": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part III. The use of Hammett equation for kinetic investigation of 2-sulfanilamidopyrimidine derivatives autoxidation. General first-order rate constants for autoxidation of sulfadiazine, sulfamerazine, sulfadimidine, sulfaperine and sulfamethoxydiazine in the air oxygen atmosphere, in solutions of pH 4-7, at 403, 411 and 418 K were determined from the absorbance measurements in 0-1 mole/dm3 HCl at 243 or 333 nm, using the so-called \"subtraction technique\". The thermodynamic parameters of this reaction were determined (deltaHa, deltaH not equal to, deltaS not equal to, deltaG not equal to and logA). The effect of the substituents in positions 4, 5 and 6 of the pyrimidine ring on the rate of autoxidation was interpreted in terms of the Hammett equation."}
{"id": "PMID:20615", "title": "Purification and properties of a ribonuclease in human urine that hydrolyses polycytidylic acid.", "content": "Human urine RNase was purified about 2000-fold. The preparation is free from phosphatase, phosphodiesterase and DNase activities. On electrophoresis through polyacrylamide gel at pH 8.3, it migrates toward the anode and stains with periodic acid-Schiff reagent, suggesting that it is acidic and glycoprotein in nature. Its isoelectric point is at pH 4.1. It has a molecular weight of about 21,500. It is thermostable at pH 4.2 and thermolabile at pH 8.5. It has a pH optimum at 6.5. It exhibits highest preference for cytidine 3'-phosphate linkages. Its activity on poly (C) is endonucleolytic. It cleaves poly (C) via intramolecular transphosphorylation. It has no action on cytidine 2': 3'-cyclic phosphate or uridine 2':3'-cyclic phosphate. Its rate of hydrolysis of poly (U) is less than 2% of that of poly C). Poly (A) and poly (G) are totally inert to its action. Its action on poly (C) is inhibited by poly (G), poly (A) and poly (U). It differs from bovine pancreatic Rnase A in its physical, chemical and catalytic properties. It is, however, similar to human serum and pancreatic RNase in all its properties, suggesting that pancreas is its likely source.", "contents": "Purification and properties of a ribonuclease in human urine that hydrolyses polycytidylic acid. Human urine RNase was purified about 2000-fold. The preparation is free from phosphatase, phosphodiesterase and DNase activities. On electrophoresis through polyacrylamide gel at pH 8.3, it migrates toward the anode and stains with periodic acid-Schiff reagent, suggesting that it is acidic and glycoprotein in nature. Its isoelectric point is at pH 4.1. It has a molecular weight of about 21,500. It is thermostable at pH 4.2 and thermolabile at pH 8.5. It has a pH optimum at 6.5. It exhibits highest preference for cytidine 3'-phosphate linkages. Its activity on poly (C) is endonucleolytic. It cleaves poly (C) via intramolecular transphosphorylation. It has no action on cytidine 2': 3'-cyclic phosphate or uridine 2':3'-cyclic phosphate. Its rate of hydrolysis of poly (U) is less than 2% of that of poly C). Poly (A) and poly (G) are totally inert to its action. Its action on poly (C) is inhibited by poly (G), poly (A) and poly (U). It differs from bovine pancreatic Rnase A in its physical, chemical and catalytic properties. It is, however, similar to human serum and pancreatic RNase in all its properties, suggesting that pancreas is its likely source."}
{"id": "PMID:20613", "title": "Kinetics of drug decomposition. Part 48. Specific acid-base hydrolysis of rolitetracycline.", "content": "Using chromatographic-spectrophotometric method, the effect of H+ and OH- ions on the rate of hydrolysis of rolitetracycline (RT) to tetracycline (T) at 20degreeC was investigated. The advantage of this analytical procedure over the direct fluorescence or UV absorption measurements of RT solutions during the kinetic investigations in HCl medium was demonstrated. The catalytic rate constants (kH+ and kOH-) for the hydrolytic degradation of RT under oxygen-free conditions are given.", "contents": "Kinetics of drug decomposition. Part 48. Specific acid-base hydrolysis of rolitetracycline. Using chromatographic-spectrophotometric method, the effect of H+ and OH- ions on the rate of hydrolysis of rolitetracycline (RT) to tetracycline (T) at 20degreeC was investigated. The advantage of this analytical procedure over the direct fluorescence or UV absorption measurements of RT solutions during the kinetic investigations in HCl medium was demonstrated. The catalytic rate constants (kH+ and kOH-) for the hydrolytic degradation of RT under oxygen-free conditions are given."}
{"id": "PMID:20617", "title": "[Properties of urease immobilized by chemical binding to a derivatives of cellulose].", "content": "A comparative study of properties of soluble urease and urease immobilized by its binding to cellulose derivatives was carried out. Upon chemical binding of urease to cellulose derivatives the Mikhaelis constant and pH optimum for the enzyme action changed insignificantly. Maximum enzymic activity of soluble and immobilized urease occurred at 50 degrees C. The energy of activation of urea hydrolysis by urease during enzyme immobilization also changed insignificantly.", "contents": "[Properties of urease immobilized by chemical binding to a derivatives of cellulose]. A comparative study of properties of soluble urease and urease immobilized by its binding to cellulose derivatives was carried out. Upon chemical binding of urease to cellulose derivatives the Mikhaelis constant and pH optimum for the enzyme action changed insignificantly. Maximum enzymic activity of soluble and immobilized urease occurred at 50 degrees C. The energy of activation of urea hydrolysis by urease during enzyme immobilization also changed insignificantly."}
{"id": "PMID:20620", "title": "Primary photochemical event in vision: proton translocation.", "content": "Picosecond studies of rhodopsin in low-temperature glasses have been carried out in order to observe directly the risetime of prelumirhodopsin, the first intermediate in the visual pathway. Only at 20 K or below can the risetime of this intermediate be resolved and even at 4 K it is astoundingly rapid, about 36 psec. An examination of the Arrhenius dependence on temperature of the rate of formation of prelumirhodopsin shows a strong deviation from linearity at low temperatures, i.e., non-Arrhenius behavior. This marked non-linear behavior is characteristic of a quantum mechanical tunneling event such as the translocation of hydrogen. An excellent candidate for the tunnelling process is the hydrogen of the protonated Schiff base formed between opsin and its retinal chromophore. Deuterium-exchanged rhodopsin, in which the Schiff base hydrogen is replaced by a deuterium, also shows a marked non-Arrhenius temperature dependence at low temperatures, consistent with tunneling. The rate of formation of prelumirhodopsin in deuterium-exchanged samples is much slower and a deuterium isotope effect kH/kD approximately or equal to 7 is observed. The data support a model in which the formation of prelumirhodopsin involves translocation of a proton toward the Schiff base nitrogen of the retinal chromophore.", "contents": "Primary photochemical event in vision: proton translocation. Picosecond studies of rhodopsin in low-temperature glasses have been carried out in order to observe directly the risetime of prelumirhodopsin, the first intermediate in the visual pathway. Only at 20 K or below can the risetime of this intermediate be resolved and even at 4 K it is astoundingly rapid, about 36 psec. An examination of the Arrhenius dependence on temperature of the rate of formation of prelumirhodopsin shows a strong deviation from linearity at low temperatures, i.e., non-Arrhenius behavior. This marked non-linear behavior is characteristic of a quantum mechanical tunneling event such as the translocation of hydrogen. An excellent candidate for the tunnelling process is the hydrogen of the protonated Schiff base formed between opsin and its retinal chromophore. Deuterium-exchanged rhodopsin, in which the Schiff base hydrogen is replaced by a deuterium, also shows a marked non-Arrhenius temperature dependence at low temperatures, consistent with tunneling. The rate of formation of prelumirhodopsin in deuterium-exchanged samples is much slower and a deuterium isotope effect kH/kD approximately or equal to 7 is observed. The data support a model in which the formation of prelumirhodopsin involves translocation of a proton toward the Schiff base nitrogen of the retinal chromophore."}
{"id": "PMID:20618", "title": "[Denaturation of the alpha-amylase of Bacillus subtilis in an acid medium].", "content": "By fractionation of purine compounds (sorbtion on the cation exchange resin KU-2 (H+), extraction, precipitation of purine compounds as Ag-complexes) a \"purine fraction\" of the culture liquid epiphytic bacteria No. 703 isolated from barley overground organs was obtained. The presence of isopentenyl cytokinins was demonstrated by quality reactions of the purine fraction with aromatic amines and phenols as well as by the values of Rf and UV spectrum of individual compounds examined by paper chromatography of the purine fraction.", "contents": "[Denaturation of the alpha-amylase of Bacillus subtilis in an acid medium]. By fractionation of purine compounds (sorbtion on the cation exchange resin KU-2 (H+), extraction, precipitation of purine compounds as Ag-complexes) a \"purine fraction\" of the culture liquid epiphytic bacteria No. 703 isolated from barley overground organs was obtained. The presence of isopentenyl cytokinins was demonstrated by quality reactions of the purine fraction with aromatic amines and phenols as well as by the values of Rf and UV spectrum of individual compounds examined by paper chromatography of the purine fraction."}
{"id": "PMID:20621", "title": "Sodium-stimulated glutamate uptake in membrane vesicles of Escherichia coli: the role of ion gradients.", "content": "Membrane vesicles prepared from Escherichia coli B/r grown on glutamate as a sole source of carbon and energy require sodium for glutamate accumulation when energized by D-lactate oxidation. Glutamate uptake can also be driven by a prearranged sodium gradient (out to in) in the absence of an energy source or a protonmotive force. Sodium ions are exchanged rapidly in respiring vesicles and the sodium gradient may be large enough under certain conditions to drive glutamate uptake after the protonmotive force is abolished with m-chlorocarbonylcyanide phenylhydrazone. Glutamate uptake due to a prearranged sodium gradient or lactate oxidation is inhibited by monensin but not by nigericin. Transport does not occur in response to valinomycin-induced membrane potential. We interpret these results to indicate that glutamate transport is obligately coupled to sodium transport and can only occur when there is a net flux of sodium ions. This flux is driven by a chemical gradient of sodium that is created by the protonmotive force generated by respiration.", "contents": "Sodium-stimulated glutamate uptake in membrane vesicles of Escherichia coli: the role of ion gradients. Membrane vesicles prepared from Escherichia coli B/r grown on glutamate as a sole source of carbon and energy require sodium for glutamate accumulation when energized by D-lactate oxidation. Glutamate uptake can also be driven by a prearranged sodium gradient (out to in) in the absence of an energy source or a protonmotive force. Sodium ions are exchanged rapidly in respiring vesicles and the sodium gradient may be large enough under certain conditions to drive glutamate uptake after the protonmotive force is abolished with m-chlorocarbonylcyanide phenylhydrazone. Glutamate uptake due to a prearranged sodium gradient or lactate oxidation is inhibited by monensin but not by nigericin. Transport does not occur in response to valinomycin-induced membrane potential. We interpret these results to indicate that glutamate transport is obligately coupled to sodium transport and can only occur when there is a net flux of sodium ions. This flux is driven by a chemical gradient of sodium that is created by the protonmotive force generated by respiration."}
{"id": "PMID:20619", "title": "[Metabolism of sex steroid hormones in neuroendocrine organs. I. In vitro androgen metabolism in the hypophyses and epiphyses of rats during the puberal period].", "content": "Metabolism of tritium-labeled testosterone, delta4-androstane-3, 17-dion, dihydrotestosterone. 5alpha-androstane-3alpha, 17beta-diod and 5alpha-androstane-3beta, 17beta-dion by the isolated hypophyses and epiphyses of male and female 30-day rats was studied. The glands were incubated in Eagle's medium containing the mentioned androgens with the concentration of 1-2.10(-8) M for 90 min at 37 degrees C. As revealed, restoration of testosterone and delta4 androstane-3, 17-dion by 5alpha-reductase occurred in  the epiphyses and hypophyses; under conditions of incubation androgen hydroxylation was realized only in the 3alpha- and 17beta-positions. Organ and sexual specificity of the androgen metabolism in the hypophyses and the epiphyses was quantitative in character: the metabolism level of all the androgens was greater in female rats than in the male both in the hypophysis and in the epiphyses; the activity of 5-reductase was lower in the epiphyses of animals of the both sexes than in the hypophyses. It appeared that in the process of biotransformation androgens in the organs under study served as precursors of the polar unidentified metabolites poorly retained by the tissues and eliminated from the organs into the incubation medium during the incubation.", "contents": "[Metabolism of sex steroid hormones in neuroendocrine organs. I. In vitro androgen metabolism in the hypophyses and epiphyses of rats during the puberal period]. Metabolism of tritium-labeled testosterone, delta4-androstane-3, 17-dion, dihydrotestosterone. 5alpha-androstane-3alpha, 17beta-diod and 5alpha-androstane-3beta, 17beta-dion by the isolated hypophyses and epiphyses of male and female 30-day rats was studied. The glands were incubated in Eagle's medium containing the mentioned androgens with the concentration of 1-2.10(-8) M for 90 min at 37 degrees C. As revealed, restoration of testosterone and delta4 androstane-3, 17-dion by 5alpha-reductase occurred in  the epiphyses and hypophyses; under conditions of incubation androgen hydroxylation was realized only in the 3alpha- and 17beta-positions. Organ and sexual specificity of the androgen metabolism in the hypophyses and the epiphyses was quantitative in character: the metabolism level of all the androgens was greater in female rats than in the male both in the hypophysis and in the epiphyses; the activity of 5-reductase was lower in the epiphyses of animals of the both sexes than in the hypophyses. It appeared that in the process of biotransformation androgens in the organs under study served as precursors of the polar unidentified metabolites poorly retained by the tissues and eliminated from the organs into the incubation medium during the incubation."}
{"id": "PMID:20622", "title": "Fatty acid synthetase from Brevibacterium ammoniagenes: formation of monounsaturated fatty acids by a multienzyme complex.", "content": "A multienzyme fatty acid synthetase complex isolated from Brevibacterium ammoniagenes has been purified to a specific activity of 1440 nmol of malonyl-CoA incorporated per min/mg. The enzyme is homogeneous, as judged by gel electrophoresis on agarose gels, and has a molecular weight of 1.2 X 10(6). Both NADPH and NADH are required for activity. In contrast to other fatty acid synthetase complexes, the enzyme catalyzes the synthesis of both long-chain saturated and monounsaturated fatty acids from malonyl-CoA and acetyl-CoA. The formation of unsaturated fatty acids is oxygen-independent and sharply reduced by 3-decynoyl-N-acetylcysteamine, a known inhibitor of Escherchia coli beta-hydroxydecanoyl thioester dehydrase (EC 4.2.1.60).", "contents": "Fatty acid synthetase from Brevibacterium ammoniagenes: formation of monounsaturated fatty acids by a multienzyme complex. A multienzyme fatty acid synthetase complex isolated from Brevibacterium ammoniagenes has been purified to a specific activity of 1440 nmol of malonyl-CoA incorporated per min/mg. The enzyme is homogeneous, as judged by gel electrophoresis on agarose gels, and has a molecular weight of 1.2 X 10(6). Both NADPH and NADH are required for activity. In contrast to other fatty acid synthetase complexes, the enzyme catalyzes the synthesis of both long-chain saturated and monounsaturated fatty acids from malonyl-CoA and acetyl-CoA. The formation of unsaturated fatty acids is oxygen-independent and sharply reduced by 3-decynoyl-N-acetylcysteamine, a known inhibitor of Escherchia coli beta-hydroxydecanoyl thioester dehydrase (EC 4.2.1.60)."}
{"id": "PMID:20623", "title": "Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations.", "content": "Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue preparations and was greatest (19- to 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal muscle, adrenal, and epididymal fat. Activation was also observed with partially purified preparations of guanylate cyclase. Activation of rat liver supernatant preparations was augmented slightly with reducing agents, decreased with some oxidizing agents, and greater in a nitrogen than in an oxygen atmosphere. After activation with NO, guanylate cyclase activity decreased with a half-life of 3-4 at 4 degrees but re-exposure to NO resulted in reactivation of preparations. Sodium azide, sodium nitrite, hydroxylamine, and sodium nitroprusside also increased guanylate cyclase activity as reported previously. NO alone and in combination with these agents produced approximately the same degree of maximal activation, suggesting that all of these agents act through a similar mechanism. NO also increased the accumulation of cyclic GMP but not cyclic AMP in incubations of minces from various rat tissues. We propose that various nitro compounds and those capable of forming NO in incubations activate guanylate cyclase through a similar but undefined mechanism. These effects may explain the high activities of guanylate cyclase in certain tissues (e.g., lung and intestinal mucosa) that are exposed to environmental nitro compounds.", "contents": "Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations. Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue preparations and was greatest (19- to 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal muscle, adrenal, and epididymal fat. Activation was also observed with partially purified preparations of guanylate cyclase. Activation of rat liver supernatant preparations was augmented slightly with reducing agents, decreased with some oxidizing agents, and greater in a nitrogen than in an oxygen atmosphere. After activation with NO, guanylate cyclase activity decreased with a half-life of 3-4 at 4 degrees but re-exposure to NO resulted in reactivation of preparations. Sodium azide, sodium nitrite, hydroxylamine, and sodium nitroprusside also increased guanylate cyclase activity as reported previously. NO alone and in combination with these agents produced approximately the same degree of maximal activation, suggesting that all of these agents act through a similar mechanism. NO also increased the accumulation of cyclic GMP but not cyclic AMP in incubations of minces from various rat tissues. We propose that various nitro compounds and those capable of forming NO in incubations activate guanylate cyclase through a similar but undefined mechanism. These effects may explain the high activities of guanylate cyclase in certain tissues (e.g., lung and intestinal mucosa) that are exposed to environmental nitro compounds."}
{"id": "PMID:20624", "title": "Unequivocal demonstration of fructose-1,6-bisphosphatase in mammalian brain.", "content": "Fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase; EC 3.1.3.11) has been found in rat brain and identified unequivocally. The enzyme has been purified to 95% homogeneity by standard procedures, including adsorption to a phosphocellulose column followed by elution with substrate. The purified enzyme exhibits a broad optimum above pH 7.6. Both fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate are substrates of this enzyme; the hydrolysis of the latter occurs at about 20% of the rate of the former, and the Km for fructose 1,6-bisphosphate is approximately 1.32 X 10(-4) M. 5'-AMP, an inhibitor of other mammalian-fructose-1,6-bisphosphatases, is without effect, and in further contrast with the other enzymes there is no metal requirement for activity. Purified brain enzyme fails to crossreact with the antibody prepared against the purified liver fructose-1,6-bisphosphatase. On the other hand, antiserum produced against the brain fructose-1,6-bisphosphatase quantitatively precipitates the enzyme activity and forms precipitin bands with preparations of brain fructose-1,6-bisphosphatase.", "contents": "Unequivocal demonstration of fructose-1,6-bisphosphatase in mammalian brain. Fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase; EC 3.1.3.11) has been found in rat brain and identified unequivocally. The enzyme has been purified to 95% homogeneity by standard procedures, including adsorption to a phosphocellulose column followed by elution with substrate. The purified enzyme exhibits a broad optimum above pH 7.6. Both fructose 1,6-bisphosphate and sedoheptulose 1,7-bisphosphate are substrates of this enzyme; the hydrolysis of the latter occurs at about 20% of the rate of the former, and the Km for fructose 1,6-bisphosphate is approximately 1.32 X 10(-4) M. 5'-AMP, an inhibitor of other mammalian-fructose-1,6-bisphosphatases, is without effect, and in further contrast with the other enzymes there is no metal requirement for activity. Purified brain enzyme fails to crossreact with the antibody prepared against the purified liver fructose-1,6-bisphosphatase. On the other hand, antiserum produced against the brain fructose-1,6-bisphosphatase quantitatively precipitates the enzyme activity and forms precipitin bands with preparations of brain fructose-1,6-bisphosphatase."}
{"id": "PMID:20625", "title": "Resonance Raman spectroscopy of arsanilazocarboxypeptidase A: determination of the nature of the azotyrosyl-248-zinc complex.", "content": "Resonance Raman spectra of arsanilazotryosyl-248 carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.12.2) exhibit only the vibrational bands of its chromophoric azotyrosyl-248 residue uncomplicated by background interference from either water or other components of the protein. The resonance Raman spectra contain multiple, discrete bands which change as a function of pH, thereby demonstrating the existence of interconvertible species of the azotyrosine probe in solution. Spectra of model azophenols and of the apoazoenzyme establish the identity of these species. All conclusions about the azoenzyme based on the resonance Raman spectra, including the apparent pK values for the interconversion of these species, are in complete agreement with those drawn earlier from studies by absorption spectroscopy. In addition, the properties of resonance Raman bands that have been identified with the motions of specific atoms of azotyrosyl-248 provide details of the interactions of specific atoms of this chromophore with the catalytic zinc atom at the active site. In particular, this has allowed elucidation of the structure of the azotyrosyl-248-zinc coordination complex. Such experiments are also providing information on the effects of crystallization on the enzyme and on its interaction with inhibitors. The important potential of resonance Raman spectroscopy for the study of the structure of chromophoric components of active enzymatic sites and of metal complex ions is discussed.", "contents": "Resonance Raman spectroscopy of arsanilazocarboxypeptidase A: determination of the nature of the azotyrosyl-248-zinc complex. Resonance Raman spectra of arsanilazotryosyl-248 carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.12.2) exhibit only the vibrational bands of its chromophoric azotyrosyl-248 residue uncomplicated by background interference from either water or other components of the protein. The resonance Raman spectra contain multiple, discrete bands which change as a function of pH, thereby demonstrating the existence of interconvertible species of the azotyrosine probe in solution. Spectra of model azophenols and of the apoazoenzyme establish the identity of these species. All conclusions about the azoenzyme based on the resonance Raman spectra, including the apparent pK values for the interconversion of these species, are in complete agreement with those drawn earlier from studies by absorption spectroscopy. In addition, the properties of resonance Raman bands that have been identified with the motions of specific atoms of azotyrosyl-248 provide details of the interactions of specific atoms of this chromophore with the catalytic zinc atom at the active site. In particular, this has allowed elucidation of the structure of the azotyrosyl-248-zinc coordination complex. Such experiments are also providing information on the effects of crystallization on the enzyme and on its interaction with inhibitors. The important potential of resonance Raman spectroscopy for the study of the structure of chromophoric components of active enzymatic sites and of metal complex ions is discussed."}
{"id": "PMID:20626", "title": "Selective inhibition of gamma-glutamyl-cycle enzymes by substrate analogs.", "content": "Substrate analogs have been obtained that selectively inhibit the reactions of the gamma-glutamyl cycle or that are susceptible to only limited metabolism by the cycle. Thus, glutathione synthesis may be inhibited and analogs of glutathione may be synthesized that do not participate in transpeptidation. Specific inhibitors of gamma-glutamylcyclotransferase and 5-oxoprolinase have been obtained. The findings offer new approaches to the in vivo study of the cycle and also to the design of more specifically directed analogs of inhibitors such as methionine sulfoximine and 6-diazo-5-oxonorleucine.", "contents": "Selective inhibition of gamma-glutamyl-cycle enzymes by substrate analogs. Substrate analogs have been obtained that selectively inhibit the reactions of the gamma-glutamyl cycle or that are susceptible to only limited metabolism by the cycle. Thus, glutathione synthesis may be inhibited and analogs of glutathione may be synthesized that do not participate in transpeptidation. Specific inhibitors of gamma-glutamylcyclotransferase and 5-oxoprolinase have been obtained. The findings offer new approaches to the in vivo study of the cycle and also to the design of more specifically directed analogs of inhibitors such as methionine sulfoximine and 6-diazo-5-oxonorleucine."}
{"id": "PMID:20627", "title": "Quantum efficiency of photosynthetic energy conversion.", "content": "The quantum efficiency of photosynthetic energy conversion was investigated in isolated spinach chloroplasts by measurements of the quantum requirements of ATP formation by cyclic and noncyclic photophosphorylation catalyzed by ferredoxin. ATP formation had a requirement of about 2 quanta per 1 ATP at 715 nm (corresponding to a requirement of 1 quantum per electron) and a requirement of 4 quanta per ATP (corresponding to a requirement of 2 quanta per electron) at 554 nm. When cyclic and noncyclic photophosphorylation were operating concurrently at 554 nm, a total of about 12 quanta was required to generate the two NADPH and three ATP needed for the assimilation of one CO2 to the level of glucose.", "contents": "Quantum efficiency of photosynthetic energy conversion. The quantum efficiency of photosynthetic energy conversion was investigated in isolated spinach chloroplasts by measurements of the quantum requirements of ATP formation by cyclic and noncyclic photophosphorylation catalyzed by ferredoxin. ATP formation had a requirement of about 2 quanta per 1 ATP at 715 nm (corresponding to a requirement of 1 quantum per electron) and a requirement of 4 quanta per ATP (corresponding to a requirement of 2 quanta per electron) at 554 nm. When cyclic and noncyclic photophosphorylation were operating concurrently at 554 nm, a total of about 12 quanta was required to generate the two NADPH and three ATP needed for the assimilation of one CO2 to the level of glucose."}
{"id": "PMID:20628", "title": "Embryologic development of a mouse sympathetic ganglion in vivo and in vitro.", "content": "The morphologic and biochemical development of the embryonic mouse superior cervical ganglion was characterized in vivo and in tissue culture. From 13 days of gestation, when the superior cervical ganglion was first visible, to birth at 19 days, tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] activity increased 100-fold in vivo. Explants of ganglia from 14-day embryos exhibited abundant neurite outgrowth in basal medium without added nerve growth factor (NGF), and increases in tyrosine hydroxylase activity paralleled that observed in vivo. Ganglia from 14-day embryos elaborated neurites and exhibited 3-fold increases in enzyme activity in vitro in the presence of antiserum to NGF (anti-NGF) or NGF + anti-NGF. In direct contrast, ganglia from 18-day fetuses failed to grow without added NGF or in medium containing anti-NGF or NGF + anti-NGF: virtually no axon outgrowth occurred and tyrosine hydroxylase activity decreased by half. These observations suggest that developmental regulatory mechanisms change radically during embryologic and fetal life of mammalian superior cervical ganglion.", "contents": "Embryologic development of a mouse sympathetic ganglion in vivo and in vitro. The morphologic and biochemical development of the embryonic mouse superior cervical ganglion was characterized in vivo and in tissue culture. From 13 days of gestation, when the superior cervical ganglion was first visible, to birth at 19 days, tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] activity increased 100-fold in vivo. Explants of ganglia from 14-day embryos exhibited abundant neurite outgrowth in basal medium without added nerve growth factor (NGF), and increases in tyrosine hydroxylase activity paralleled that observed in vivo. Ganglia from 14-day embryos elaborated neurites and exhibited 3-fold increases in enzyme activity in vitro in the presence of antiserum to NGF (anti-NGF) or NGF + anti-NGF. In direct contrast, ganglia from 18-day fetuses failed to grow without added NGF or in medium containing anti-NGF or NGF + anti-NGF: virtually no axon outgrowth occurred and tyrosine hydroxylase activity decreased by half. These observations suggest that developmental regulatory mechanisms change radically during embryologic and fetal life of mammalian superior cervical ganglion."}
{"id": "PMID:20629", "title": "Thyrotropin-releasing hormone-like material in the rat retina: changes due to environmental lighting.", "content": "Material reacting with an antibody to thyrotropin-releasing hormone (TRH) has been found to be present in the rat retina. The compound present in the retina cochromatographed with authentic TRH and most of its activity was lost when incubated with pyroglutamate aminopeptidase (L-pyroglutamyl-peptide hydrolase, EC 3.4.11.8), an enzyme that degrades TRH. The TRH-like activity in the rat retina was low during the night and high during the day. There was a 4-hr lag period after the lights were turned on before peak TRH levels were attained. A decrease in TRH was seen after 2 hr of darkness and the level of TRH was lowest after 4 hr of darkness. Retinal TRH is elevated by environmental lighting regardless of the time of the day. These findings suggest that TRH may be involved in retinal photorecptive mechanisms.", "contents": "Thyrotropin-releasing hormone-like material in the rat retina: changes due to environmental lighting. Material reacting with an antibody to thyrotropin-releasing hormone (TRH) has been found to be present in the rat retina. The compound present in the retina cochromatographed with authentic TRH and most of its activity was lost when incubated with pyroglutamate aminopeptidase (L-pyroglutamyl-peptide hydrolase, EC 3.4.11.8), an enzyme that degrades TRH. The TRH-like activity in the rat retina was low during the night and high during the day. There was a 4-hr lag period after the lights were turned on before peak TRH levels were attained. A decrease in TRH was seen after 2 hr of darkness and the level of TRH was lowest after 4 hr of darkness. Retinal TRH is elevated by environmental lighting regardless of the time of the day. These findings suggest that TRH may be involved in retinal photorecptive mechanisms."}
{"id": "PMID:20630", "title": "Stimulation of human platelet guanylate cyclase by unsaturated fatty acid peroxides.", "content": "Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity of human platelet homogenates was stimulated by the addition of phospholipase A2 or unsaturated fatty acids such as oleic, vaccenic, linoleic, linolenic, eicosenoic, eicosadienoic, and arachidonic acids. The addition of lipoxidase potentiated the fatty acid-induced stimulation of guanylate cyclase purified by DEAE-cellulose column chromatography. The extent of the stimulation was dependent on the concentration of the oxidized form of these fatty acids (peroxides). Saturated fatty acids such as stearic and arachidic acids had no effect on the guanylate cyclase activity in the presence or absence of lipoxidase, indicating that human plateletguanylate cyclase is stimulated by unsaturated fatty acid peroxides rather than by fatty acids. Hemoglobin prevented the enzyme stimulation produced by low concentrations of fatty acid peroxides, but enhanced stimulation of the enzyme activity with high concentrations of fatty acid peroxides. 2-Mercaptoethanol, dithiothreitol, and N-ethylmaleimide inhibited the guanylate cyclase activities both in the presence and absence of unsaturated fatty acidperoxide. The stimulation of guanylate cyclase activity by unsaturated fatty acid peroxidesis attributed to oxidation of sulfhydryl residues of the enzyme protein.", "contents": "Stimulation of human platelet guanylate cyclase by unsaturated fatty acid peroxides. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity of human platelet homogenates was stimulated by the addition of phospholipase A2 or unsaturated fatty acids such as oleic, vaccenic, linoleic, linolenic, eicosenoic, eicosadienoic, and arachidonic acids. The addition of lipoxidase potentiated the fatty acid-induced stimulation of guanylate cyclase purified by DEAE-cellulose column chromatography. The extent of the stimulation was dependent on the concentration of the oxidized form of these fatty acids (peroxides). Saturated fatty acids such as stearic and arachidic acids had no effect on the guanylate cyclase activity in the presence or absence of lipoxidase, indicating that human plateletguanylate cyclase is stimulated by unsaturated fatty acid peroxides rather than by fatty acids. Hemoglobin prevented the enzyme stimulation produced by low concentrations of fatty acid peroxides, but enhanced stimulation of the enzyme activity with high concentrations of fatty acid peroxides. 2-Mercaptoethanol, dithiothreitol, and N-ethylmaleimide inhibited the guanylate cyclase activities both in the presence and absence of unsaturated fatty acidperoxide. The stimulation of guanylate cyclase activity by unsaturated fatty acid peroxidesis attributed to oxidation of sulfhydryl residues of the enzyme protein."}
{"id": "PMID:20631", "title": "Purification and properties of human erythrocyte pyrimidine 5'-nucleotidase.", "content": "A 250,000-fold purification of pyrimidine 5'-nucleotidase from human erythrocytes has been achieved using a combination of DEAE-cellulose chromatography, ammonium sulfate fractionation, gel filtration, and isoelectric focusing. Polyacrylamide disc and starch gel electrophoresis of the purified material show two strong protein bands. On starch gel these bands exhibited pyrimidine 5'-nucleotidase activity. Two faint protein bands devoid of enzyme activity were also found in the case of polyacrylamide electrophoresis. The enzyme has a pH optimum at 7.5 and is most stable between pH 6 and 7.5. The enzyme has pI of 5.0 and a molecular weight of 28,000 by gel filtration. The Km of the purified enzyme was 10 muM, compared to 40 muM when measured in hemolysate. The higher Km in the hemolysate is due to the presence of an inhibitor. Inorganic phosphate was shown to be a competitive inhibitor of pyrimidine 5'-nucleotidase and inorganic phosphate in the hemolysate may be responsible for increasing the Km of the enzyme for the substrate cytidine monophosphate.", "contents": "Purification and properties of human erythrocyte pyrimidine 5'-nucleotidase. A 250,000-fold purification of pyrimidine 5'-nucleotidase from human erythrocytes has been achieved using a combination of DEAE-cellulose chromatography, ammonium sulfate fractionation, gel filtration, and isoelectric focusing. Polyacrylamide disc and starch gel electrophoresis of the purified material show two strong protein bands. On starch gel these bands exhibited pyrimidine 5'-nucleotidase activity. Two faint protein bands devoid of enzyme activity were also found in the case of polyacrylamide electrophoresis. The enzyme has a pH optimum at 7.5 and is most stable between pH 6 and 7.5. The enzyme has pI of 5.0 and a molecular weight of 28,000 by gel filtration. The Km of the purified enzyme was 10 muM, compared to 40 muM when measured in hemolysate. The higher Km in the hemolysate is due to the presence of an inhibitor. Inorganic phosphate was shown to be a competitive inhibitor of pyrimidine 5'-nucleotidase and inorganic phosphate in the hemolysate may be responsible for increasing the Km of the enzyme for the substrate cytidine monophosphate."}
{"id": "PMID:20632", "title": "Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding.", "content": "[3H]Diazepam appears to bind specifically to a single, saturable, binding site located on rat brain membranes, with an affinity constant near 3 nM at pH 7.4. Specific binding constitutes more than 90% of total binding at 0 degrees and less than 10% of total binding at 37 degrees. Arrhenius plots suggest a sharp conformational change in the diazepam receptor near 18 degrees. Mitochondrial fractions from rat kidney, liver, and lung exhibit some [3H]diazepam binding that can be displaced by nonradioactive diazepam and several other benzodiazepines. However, Ro-4864, which is almost inactive in displacing [3H]diazepam from brain membranes, is extremely potent in displacing it from kidney mitochondria. Conversely, clonazepam, the most potent inhibitor of brain binding, is an extremely weak inhibitor of kidney binding. Furthermore, diazepam binding to kidney mitochondria has an affinity constantof 40 nM, about 15 times higher than that in brain. No specific diazepam binding was detected in intestine or skeletal muscle. Thus, specific [3H]diazepam binding to membranes appears to be restricted to brain, where it is unevenly distributed: the density of diazepam receptors is about five times higher in cortex (the highest density) than in pons-meddula (lowest density). Trypsin and chymotrypsin completely abolished specific [3H]diazepambinding in brain and kidney.", "contents": "Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. [3H]Diazepam appears to bind specifically to a single, saturable, binding site located on rat brain membranes, with an affinity constant near 3 nM at pH 7.4. Specific binding constitutes more than 90% of total binding at 0 degrees and less than 10% of total binding at 37 degrees. Arrhenius plots suggest a sharp conformational change in the diazepam receptor near 18 degrees. Mitochondrial fractions from rat kidney, liver, and lung exhibit some [3H]diazepam binding that can be displaced by nonradioactive diazepam and several other benzodiazepines. However, Ro-4864, which is almost inactive in displacing [3H]diazepam from brain membranes, is extremely potent in displacing it from kidney mitochondria. Conversely, clonazepam, the most potent inhibitor of brain binding, is an extremely weak inhibitor of kidney binding. Furthermore, diazepam binding to kidney mitochondria has an affinity constantof 40 nM, about 15 times higher than that in brain. No specific diazepam binding was detected in intestine or skeletal muscle. Thus, specific [3H]diazepam binding to membranes appears to be restricted to brain, where it is unevenly distributed: the density of diazepam receptors is about five times higher in cortex (the highest density) than in pons-meddula (lowest density). Trypsin and chymotrypsin completely abolished specific [3H]diazepambinding in brain and kidney."}
{"id": "PMID:20633", "title": "Kinetics of the alkaline tetramer leads to dimer dissociation in liganded human hemoglobin: a laser light-scattering stopped-flow study.", "content": "The first-order dissociation of tetrameric HbCO to the dimer has been studied overthe pH range 10.30-11.57 in a light-scattering stopped-flow apparatus using argon-ion laser excitation. The first-order dissociation rate constant varies from 0.25 sec-1 to 24.0 sec-1over this pH interval. A semilogarithmic plot of k versus pH has a slope of 2.56 at pH 11.07, the midpoint. The pH dependence of the dissociation of the tetramer is consistent with progressive titration of alpha1-alpha2 and beta1-beta2 salt bridges. At pH 10.66, the dissociation rates of HbO2, HbCO, methemoglobin, and HbCN vary less than 20% from their mean value. A study of the dissociation kinetics as a function of protein concentration allows one to obtain both association and dissociation rate constants, and hence equilibrium constants, for the tetramer in equilibrium dimer reaction. In this manner, equilibrium constants were obtained on protein solutions with less than 15 sec of exposure to dissociating conditions.", "contents": "Kinetics of the alkaline tetramer leads to dimer dissociation in liganded human hemoglobin: a laser light-scattering stopped-flow study. The first-order dissociation of tetrameric HbCO to the dimer has been studied overthe pH range 10.30-11.57 in a light-scattering stopped-flow apparatus using argon-ion laser excitation. The first-order dissociation rate constant varies from 0.25 sec-1 to 24.0 sec-1over this pH interval. A semilogarithmic plot of k versus pH has a slope of 2.56 at pH 11.07, the midpoint. The pH dependence of the dissociation of the tetramer is consistent with progressive titration of alpha1-alpha2 and beta1-beta2 salt bridges. At pH 10.66, the dissociation rates of HbO2, HbCO, methemoglobin, and HbCN vary less than 20% from their mean value. A study of the dissociation kinetics as a function of protein concentration allows one to obtain both association and dissociation rate constants, and hence equilibrium constants, for the tetramer in equilibrium dimer reaction. In this manner, equilibrium constants were obtained on protein solutions with less than 15 sec of exposure to dissociating conditions."}
{"id": "PMID:20647", "title": "Antimuscarinic properties of antidepressants: dibenzepin (Noveril).", "content": "The antimuscarinic potency of dibenzepin (Noveril) was estimated by measuring (a) central in vivo effects in mice (antihypothermia and antitremor, both induced by oxotremorine), (b) peripheral in vivo activity (mydriasis caused by systemic administration of the drug), (c) the effects of dibenzepin on isolated smooth muscle from guinea pig ileum, and (d) in vitro determination of the affinity constant of dibezepine toward the muscarinic binding sites in whole mouse-brain homogenate. The data allowed the construction of a normalized antimuscarinic potency scale for some of the common tricyclic antidepressants. With a value of 1 for scopolamine, the following relative anticholinergic potencies were calculated: dibenzepin--1/600, nortriptylne--1/300, imipramine - 1/200, and amitriptyline - 1/75. These values suggest an explanation for the absence of clinically detectable anticholinergic side effects during treatment of depression with high doses of dibenzepin. Structural and spatial interrelations among various tricyclic antidepressants and scopolamine are discussed.", "contents": "Antimuscarinic properties of antidepressants: dibenzepin (Noveril). The antimuscarinic potency of dibenzepin (Noveril) was estimated by measuring (a) central in vivo effects in mice (antihypothermia and antitremor, both induced by oxotremorine), (b) peripheral in vivo activity (mydriasis caused by systemic administration of the drug), (c) the effects of dibenzepin on isolated smooth muscle from guinea pig ileum, and (d) in vitro determination of the affinity constant of dibezepine toward the muscarinic binding sites in whole mouse-brain homogenate. The data allowed the construction of a normalized antimuscarinic potency scale for some of the common tricyclic antidepressants. With a value of 1 for scopolamine, the following relative anticholinergic potencies were calculated: dibenzepin--1/600, nortriptylne--1/300, imipramine - 1/200, and amitriptyline - 1/75. These values suggest an explanation for the absence of clinically detectable anticholinergic side effects during treatment of depression with high doses of dibenzepin. Structural and spatial interrelations among various tricyclic antidepressants and scopolamine are discussed."}
{"id": "PMID:20648", "title": "[Stability of tetracycline during fermentation].", "content": "The stability of tetracycline was studied at pH 6.0 and 1.5. The thermal inactivation constant at the lower pH was found to vary between 1.62 min-1 (40 degrees C) and 65.83 min-1 (100 degrees C). A degradation mechanism was proposed in the light of the variation of entropy and steric factors.", "contents": "[Stability of tetracycline during fermentation]. The stability of tetracycline was studied at pH 6.0 and 1.5. The thermal inactivation constant at the lower pH was found to vary between 1.62 min-1 (40 degrees C) and 65.83 min-1 (100 degrees C). A degradation mechanism was proposed in the light of the variation of entropy and steric factors."}
{"id": "PMID:20652", "title": "beta-blocking agents and human fat cell adenylate cyclase.", "content": "The effects of various beta-blocking agents upon the catecholamine-activated adenylate cyclase of human fat cell ghosts were studied. Both non-selective and cardio-selective beta-blocking drugs are capable in inhibiting the human enzyme system. The concentrations of the non-selective beta-blockers (bupranolol, alprenolol, propranolol, 4-hydroxypropranolol, prindolol and oxyprenolol) required to produce half maximal inhibition of isoproterenol-stimulated rates of cAMP-formation were found to be in a narrow range (5X10(-7) M-3X10(-6) M).The cardioselective beta-blocking agents, however, were only 1/100 (methypranol) to 1/1000 (atenolol, practolol) as potent as the non-selective drugs.", "contents": "beta-blocking agents and human fat cell adenylate cyclase. The effects of various beta-blocking agents upon the catecholamine-activated adenylate cyclase of human fat cell ghosts were studied. Both non-selective and cardio-selective beta-blocking drugs are capable in inhibiting the human enzyme system. The concentrations of the non-selective beta-blockers (bupranolol, alprenolol, propranolol, 4-hydroxypropranolol, prindolol and oxyprenolol) required to produce half maximal inhibition of isoproterenol-stimulated rates of cAMP-formation were found to be in a narrow range (5X10(-7) M-3X10(-6) M).The cardioselective beta-blocking agents, however, were only 1/100 (methypranol) to 1/1000 (atenolol, practolol) as potent as the non-selective drugs."}
{"id": "PMID:20653", "title": "[The effect of sympathomimetric drugs on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)].", "content": "This study reports on effects of beta-sympathomimetic drugs on the exocrine function of the isolated cat pancreas. The injection of these drugs resulted in an increase of pancreatic protein and enzyme secretion, the excretion of calcium into the juice and the rate of volume output were not changed. The enzyme secretion was inhibited by different adrenolytic drugs (phenoxybenzamine, practolol, butoxamine), by tetracain, hemicholinium, and atropine. The pancreatic function of cats pretreated by reserpine or 6-hydroxydopamine was not altered. It is concluded, that beta-sympathomimetic drugs influence the pancreatic protein and enzyme secretion in a cholinergic way. These results are consistent with those of other investigators showing a suppressibility of the isoproterenol-induced pancreatic amylase secretion by atropine.", "contents": "[The effect of sympathomimetric drugs on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)]. This study reports on effects of beta-sympathomimetic drugs on the exocrine function of the isolated cat pancreas. The injection of these drugs resulted in an increase of pancreatic protein and enzyme secretion, the excretion of calcium into the juice and the rate of volume output were not changed. The enzyme secretion was inhibited by different adrenolytic drugs (phenoxybenzamine, practolol, butoxamine), by tetracain, hemicholinium, and atropine. The pancreatic function of cats pretreated by reserpine or 6-hydroxydopamine was not altered. It is concluded, that beta-sympathomimetic drugs influence the pancreatic protein and enzyme secretion in a cholinergic way. These results are consistent with those of other investigators showing a suppressibility of the isoproterenol-induced pancreatic amylase secretion by atropine."}
{"id": "PMID:20654", "title": "Quantifying drugs influence on cardio-respiratory synchronism.", "content": "The paper concerns the situation in which, for a considerable time, the onset of each respiratory cycle coincides with one and the same section of a cardiac cycle. A standardized procedure is described with which, in anesthetized rabbits, the potentiality of the biological mechanisms responsible for the phenomenon may be quantified. The procedure consists of progressively prolonging the cardiac cycles by selectively cooling the sinus node. Care is taken that during such procedure a situation is passed in which the respiratory cycles are a multiple of the cardiac cycles. The synchronizing kybernetic system, if any, must click in, then. As the prolonging of the cardiac cycles continues, the synchrony will get lost the sooner the weaker the potentialities of the kybernetic system and vice versa. Four drugs are tested as to their potential action on the kybernetic system. Nikethamide and methylphenidate tend to decrease its efficacy, allobarbital and benzoctamine tend to increase it, none of them, however, being conclusively effective.", "contents": "Quantifying drugs influence on cardio-respiratory synchronism. The paper concerns the situation in which, for a considerable time, the onset of each respiratory cycle coincides with one and the same section of a cardiac cycle. A standardized procedure is described with which, in anesthetized rabbits, the potentiality of the biological mechanisms responsible for the phenomenon may be quantified. The procedure consists of progressively prolonging the cardiac cycles by selectively cooling the sinus node. Care is taken that during such procedure a situation is passed in which the respiratory cycles are a multiple of the cardiac cycles. The synchronizing kybernetic system, if any, must click in, then. As the prolonging of the cardiac cycles continues, the synchrony will get lost the sooner the weaker the potentialities of the kybernetic system and vice versa. Four drugs are tested as to their potential action on the kybernetic system. Nikethamide and methylphenidate tend to decrease its efficacy, allobarbital and benzoctamine tend to increase it, none of them, however, being conclusively effective."}
{"id": "PMID:20656", "title": "A placebo-controlled, double-blind trial of Benorylate tablets in the treatment of bursitis and synovitis due to sports injury.", "content": "In this two-week study, Benoral tablets, at a 4.5 g daily dosage were compared with a matching placebo in 20 patients suffering from sports injury. Four assessments were made: pain at rest, pain on movement, tenderness and soft tissue swelling. In each case the active treatment group (benorylate) was statistically greater than that in the placebo group at one week and after two weeks' treatment.", "contents": "A placebo-controlled, double-blind trial of Benorylate tablets in the treatment of bursitis and synovitis due to sports injury. In this two-week study, Benoral tablets, at a 4.5 g daily dosage were compared with a matching placebo in 20 patients suffering from sports injury. Four assessments were made: pain at rest, pain on movement, tenderness and soft tissue swelling. In each case the active treatment group (benorylate) was statistically greater than that in the placebo group at one week and after two weeks' treatment."}
{"id": "PMID:20657", "title": "Labeling immunoelectrophoresis: a general method for increasing the sensitivity of rocket immunoelectrophoresis with 125I-labeled anti-antibodies.", "content": "In a new procedure, rocket immunoelectrophoresis is performed at pH 8.7 with rabbit antibodies and 5% polyethyleneglycol 6000 in the agarose gel. After the pH in the gel has been changed to 5 the nonprecipitated immunoglobulins are electrophorsed out of the gel simultaneously with the electrophoresis of 125I-labeled swine antibodies against rabbit IgG into the gel. The latter antibodies tag the rabbit IgG, which is not present only in the precipitates. The radioactive precipitates are visualized by autoradiography. The method permits quantification of antigens down to an amount of approximately 0.5 ng; well-defined rockets are not formed below this limit. Compared to conventional protein staining with Coomassie brilliant blue, this represents an increase in sensitivity of up to 20 times.", "contents": "Labeling immunoelectrophoresis: a general method for increasing the sensitivity of rocket immunoelectrophoresis with 125I-labeled anti-antibodies. In a new procedure, rocket immunoelectrophoresis is performed at pH 8.7 with rabbit antibodies and 5% polyethyleneglycol 6000 in the agarose gel. After the pH in the gel has been changed to 5 the nonprecipitated immunoglobulins are electrophorsed out of the gel simultaneously with the electrophoresis of 125I-labeled swine antibodies against rabbit IgG into the gel. The latter antibodies tag the rabbit IgG, which is not present only in the precipitates. The radioactive precipitates are visualized by autoradiography. The method permits quantification of antigens down to an amount of approximately 0.5 ng; well-defined rockets are not formed below this limit. Compared to conventional protein staining with Coomassie brilliant blue, this represents an increase in sensitivity of up to 20 times."}
{"id": "PMID:20658", "title": "[Therapy of childhood schizophrenia].", "content": "Due to the multifacet genesis and variability of clinical phenomenology, the therapy of childhood schizophrenia must be multidimensional. Formerly applied techniques like electroshock- and insulin-therapy are now replaced by pharmaco-therapy, primarily with phenothiazines, butyrophenones and chlorprothixens. The dosage depends on age, body weight or body surface. Because of extrapyramidal motor side effects, combinations with anticholinergic drugs may be necessary. Psychopharmaco-therapy alone, however, is insufficient. High emphasis must be placed on psychotherapy and educational guidance and counselling of the psychotic child. Participation in play groups, sports, muscial activities, arts and crafts, and acting helps make it possible to improve communication behaviour and to transform aggressive anxiety defense into stabilized control of emotions and impulses. In addition to successive integration of the psychotic child into small groups, play therapy with the single child is meaningful. In this case, a constant and confidential relation between therapist and child is extremely important and only possible if the therapist attempts to place himself into the magic-animistic phantasies of the psychotic child. He has first to learn the psychotic language of his patient in order to support more reality-oriented behaviour processes of the child's thinking, preceiving and performing later on. In this manner, the magic-omnipotent phantasies can be dissolved and an increasing orientation of the child toward reality can be encouraged. This involves strengthening and support of non-pathological ego-functions and initiation of a new level of ego-functioning. Such an integrated developmental concept can best be realized through play therapy.", "contents": "[Therapy of childhood schizophrenia]. Due to the multifacet genesis and variability of clinical phenomenology, the therapy of childhood schizophrenia must be multidimensional. Formerly applied techniques like electroshock- and insulin-therapy are now replaced by pharmaco-therapy, primarily with phenothiazines, butyrophenones and chlorprothixens. The dosage depends on age, body weight or body surface. Because of extrapyramidal motor side effects, combinations with anticholinergic drugs may be necessary. Psychopharmaco-therapy alone, however, is insufficient. High emphasis must be placed on psychotherapy and educational guidance and counselling of the psychotic child. Participation in play groups, sports, muscial activities, arts and crafts, and acting helps make it possible to improve communication behaviour and to transform aggressive anxiety defense into stabilized control of emotions and impulses. In addition to successive integration of the psychotic child into small groups, play therapy with the single child is meaningful. In this case, a constant and confidential relation between therapist and child is extremely important and only possible if the therapist attempts to place himself into the magic-animistic phantasies of the psychotic child. He has first to learn the psychotic language of his patient in order to support more reality-oriented behaviour processes of the child's thinking, preceiving and performing later on. In this manner, the magic-omnipotent phantasies can be dissolved and an increasing orientation of the child toward reality can be encouraged. This involves strengthening and support of non-pathological ego-functions and initiation of a new level of ego-functioning. Such an integrated developmental concept can best be realized through play therapy."}
{"id": "PMID:20661", "title": "Metallic contamination of food during preparation and storage: development of methods and some preliminary results.", "content": "A chemical procedure for studying trace metals leached from metallic cooking utensils and preserving cans used in the preparation and storage of food has been developed. The method consists in the destruction of the major part of organic matter with HNO3-vapour followed by a complete mineralization of residues with small amounts of HNO3 in Teflon bombs at 150-160 degrees C under a pressure of 3-12 kg/cm2, depending on the amount and composition of the samples. Subsequently, an ion-exchange step removes major components and concentrates the trace elements in a dilute HNO3-solution, suitable for analysis. The ion-exchange separation, which is performed with an automatic ion-exchange separator, is practically free from blank level problems, e.g., typically a mean of less than 2 per cent of the sample levels of the elements being determined. Preliminary results show that large amounts of aluminium are released from vessels to the water during boiling at the same pH-range which exist for most drinking water in Sweden.", "contents": "Metallic contamination of food during preparation and storage: development of methods and some preliminary results. A chemical procedure for studying trace metals leached from metallic cooking utensils and preserving cans used in the preparation and storage of food has been developed. The method consists in the destruction of the major part of organic matter with HNO3-vapour followed by a complete mineralization of residues with small amounts of HNO3 in Teflon bombs at 150-160 degrees C under a pressure of 3-12 kg/cm2, depending on the amount and composition of the samples. Subsequently, an ion-exchange step removes major components and concentrates the trace elements in a dilute HNO3-solution, suitable for analysis. The ion-exchange separation, which is performed with an automatic ion-exchange separator, is practically free from blank level problems, e.g., typically a mean of less than 2 per cent of the sample levels of the elements being determined. Preliminary results show that large amounts of aluminium are released from vessels to the water during boiling at the same pH-range which exist for most drinking water in Sweden."}
{"id": "PMID:20663", "title": "Folate conjugase: two separate activities in human jejunum.", "content": "Previous perfusion studies of the human jejunum suggested that conjugated folate is hydrolyzed on the mucosal surface. The techniques of cell fractionation and DEAE and gel chromatography led to the identification of two separate folate conjugase activities in human jejunal mucosa: one membrane-bound and concentrated in the brush border, the other soluble and intracellular. These enzyme activities exhibit different pH optima, molecular weights, and inhibition characteristics. Folate conjugase in the brush border may accomplish the initial digestion of dietary pteroylpolyglutamates.", "contents": "Folate conjugase: two separate activities in human jejunum. Previous perfusion studies of the human jejunum suggested that conjugated folate is hydrolyzed on the mucosal surface. The techniques of cell fractionation and DEAE and gel chromatography led to the identification of two separate folate conjugase activities in human jejunal mucosa: one membrane-bound and concentrated in the brush border, the other soluble and intracellular. These enzyme activities exhibit different pH optima, molecular weights, and inhibition characteristics. Folate conjugase in the brush border may accomplish the initial digestion of dietary pteroylpolyglutamates."}
{"id": "PMID:20664", "title": "Memory formation: evidence for a specific neurochemical system in the amygdala.", "content": "beta-Adrenergic antagonists injected into the amygdala complex of rats trained in a passive avoidance task produced time-dependent and dose-dependent decreases in retention of the task. In addition, the effects observed with beta-adrenergic antagonists were both stereospecific and reversed by norepinephrine. The results support a role for an amygdala beta-adrenergic system in memory processes.", "contents": "Memory formation: evidence for a specific neurochemical system in the amygdala. beta-Adrenergic antagonists injected into the amygdala complex of rats trained in a passive avoidance task produced time-dependent and dose-dependent decreases in retention of the task. In addition, the effects observed with beta-adrenergic antagonists were both stereospecific and reversed by norepinephrine. The results support a role for an amygdala beta-adrenergic system in memory processes."}
{"id": "PMID:20665", "title": "Biogenic amine synthesis defect in dihydropteridine reductase deficiency.", "content": "In the enzymatic hydroxylation of aromatic amino acids, tetrahydrobiopterin is the essential cofactor. Regeneration of tetrahydrobiopterin requires dihydropteridine reductase, without which there should be a deficiency of hydroxylated amino acids and their products, biogenic amines. Assay of biopsied brain cortex of a patient with a deficiency of dihydropteridine reductases showed low concentrations of serotonin and dopamine, and this was reflected in the concentrations of their major metabolites measured in cerebrospinal fluid from lumbar, ventricular, and subarachnoid spaces. The metabolite concentrations were restored to normal, or above normal, by treatment with specific amino acids which bypass the metabolic block at the hydroxylation step. It is postulated that the seizures and neurological deterioration of the patient were related to a deficiency in the synthesis of biogenic amine neurotransmitters.", "contents": "Biogenic amine synthesis defect in dihydropteridine reductase deficiency. In the enzymatic hydroxylation of aromatic amino acids, tetrahydrobiopterin is the essential cofactor. Regeneration of tetrahydrobiopterin requires dihydropteridine reductase, without which there should be a deficiency of hydroxylated amino acids and their products, biogenic amines. Assay of biopsied brain cortex of a patient with a deficiency of dihydropteridine reductases showed low concentrations of serotonin and dopamine, and this was reflected in the concentrations of their major metabolites measured in cerebrospinal fluid from lumbar, ventricular, and subarachnoid spaces. The metabolite concentrations were restored to normal, or above normal, by treatment with specific amino acids which bypass the metabolic block at the hydroxylation step. It is postulated that the seizures and neurological deterioration of the patient were related to a deficiency in the synthesis of biogenic amine neurotransmitters."}
{"id": "PMID:20666", "title": "[Measurement of plasma renin activity, blood volume and exchangeable sodium: an aid in the orientation of treatment of essential arterial hypertension].", "content": "95 patients with essential uncomplicated hypertension were mostly submitted to measurement of plasma renin activity, plasma volume and exchangeable sodium. According to the results of the plasma renin activity, we noted variations in blood volume and exchangeable sodium in order to determine the best possible treatment based on these data. Single treatment, based either on diuretics or beta-blockaders was rarely sufficient to bring the blood pressure down to normal. Association of these two types of drug was often very useful. Finally, a critical study of these 3 parameters was made in an economic view of investigations of the blood pressure. The plasma volume seemed to us the most useful investigation, after which came the measurement of plasma renin activity. for the exchangeable sodium seemed of little interest.", "contents": "[Measurement of plasma renin activity, blood volume and exchangeable sodium: an aid in the orientation of treatment of essential arterial hypertension]. 95 patients with essential uncomplicated hypertension were mostly submitted to measurement of plasma renin activity, plasma volume and exchangeable sodium. According to the results of the plasma renin activity, we noted variations in blood volume and exchangeable sodium in order to determine the best possible treatment based on these data. Single treatment, based either on diuretics or beta-blockaders was rarely sufficient to bring the blood pressure down to normal. Association of these two types of drug was often very useful. Finally, a critical study of these 3 parameters was made in an economic view of investigations of the blood pressure. The plasma volume seemed to us the most useful investigation, after which came the measurement of plasma renin activity. for the exchangeable sodium seemed of little interest."}
{"id": "PMID:20667", "title": "[Persistant danger of smallpox and necessity of continuing mandatory smallpox vaccination in France].", "content": "The WHO stated a short time ago that the total eradication of smallpox would occur shortly. This announcement has been contradicted by an epidemic of smallpox in Somaila which in spite of the energetic measures taken, remained in the capital from August 1976 to January 1977 then extended to 10 regions out of 16 with from January 1977 to 18 June 1977, 1 567 cases of smallpox. This is only a provisional estimation as it is increasing every week. In view of the ease and rapidity of airline communication, it is very possible that infected subjects or products arrive in France, it is necessary for doctors to be warned and counteract the present tendancy to neglect the legal requirement for smallpox vaccination.", "contents": "[Persistant danger of smallpox and necessity of continuing mandatory smallpox vaccination in France]. The WHO stated a short time ago that the total eradication of smallpox would occur shortly. This announcement has been contradicted by an epidemic of smallpox in Somaila which in spite of the energetic measures taken, remained in the capital from August 1976 to January 1977 then extended to 10 regions out of 16 with from January 1977 to 18 June 1977, 1 567 cases of smallpox. This is only a provisional estimation as it is increasing every week. In view of the ease and rapidity of airline communication, it is very possible that infected subjects or products arrive in France, it is necessary for doctors to be warned and counteract the present tendancy to neglect the legal requirement for smallpox vaccination."}
{"id": "PMID:20671", "title": "Premedication with flunitrazepam in gastro-intestinal endoscopy.", "content": "Administration of 2 mg flunitrazepam (Rohypnol; Roche) to patients before gastro-intestinal endoscopy caused significantly less anxiety and achieved significantly greater sedation than diazepam (Vallium; Roche). No differences were found between any of the trial groups with respect to ease of intubation, tolerance of the procedure, gastric peristalsis, and the state of the pylorus. Memory of the procedure was significantly less vivid in the groups who received 2 mg flunitrazepam, than in the other groups. The patients who received 2 mg flunitrazepam showed a significantly greater willingness to undergo a repeat procedure, both when asked immediately after the procedure, and when asked on the next visit. Pulse rate increased in all groups during the procedure. No change in respiratory rate or in systolic and diastolic blood pressure occurred in any group.", "contents": "Premedication with flunitrazepam in gastro-intestinal endoscopy. Administration of 2 mg flunitrazepam (Rohypnol; Roche) to patients before gastro-intestinal endoscopy caused significantly less anxiety and achieved significantly greater sedation than diazepam (Vallium; Roche). No differences were found between any of the trial groups with respect to ease of intubation, tolerance of the procedure, gastric peristalsis, and the state of the pylorus. Memory of the procedure was significantly less vivid in the groups who received 2 mg flunitrazepam, than in the other groups. The patients who received 2 mg flunitrazepam showed a significantly greater willingness to undergo a repeat procedure, both when asked immediately after the procedure, and when asked on the next visit. Pulse rate increased in all groups during the procedure. No change in respiratory rate or in systolic and diastolic blood pressure occurred in any group."}
{"id": "PMID:20672", "title": "Pediatric plastic surgery.", "content": "Each section of this article has been discussed in severe brevity. Potential pitfalls have been expanded in an attempt to be helpful to the general surgeon who attends patients with these clinical problems. Making the relatives aware of a potential complication in its broadest sense is the responsibility of the surgeon and can only be done if there is cognizance of these problems. The author hopes that this article has accomplished this purpose, albeit in a brief format.", "contents": "Pediatric plastic surgery. Each section of this article has been discussed in severe brevity. Potential pitfalls have been expanded in an attempt to be helpful to the general surgeon who attends patients with these clinical problems. Making the relatives aware of a potential complication in its broadest sense is the responsibility of the surgeon and can only be done if there is cognizance of these problems. The author hopes that this article has accomplished this purpose, albeit in a brief format."}
{"id": "PMID:20673", "title": "The effect of (+) --cyanidanol on lysosomal enzymes of I-cell fibroblasts.", "content": "(+)--Cyanidanol, a water-soluble flavonoid, when added to cultured skin fibroblasts of a patient with I-cell disease raised the intracellular concentration of beta-galactosidase but did not affect the distribution of arylsulfatase. A, alpha-mannosidase or beta-glucuronidase. The elevated accumulation of 35SO4 by I-cell, Hunter and Maroteaux-Lamy fibroblasts was decreased by the addition of (+)--cyanidanol to the culture medium, but the degradation of previously labeled, intracellular glycosaminoglycans was not. It is concluded that (+)--cyanidanol does not produce a biochemical correction of the enzymic abnormalities existing in I-cell fibroblasts.", "contents": "The effect of (+) --cyanidanol on lysosomal enzymes of I-cell fibroblasts. (+)--Cyanidanol, a water-soluble flavonoid, when added to cultured skin fibroblasts of a patient with I-cell disease raised the intracellular concentration of beta-galactosidase but did not affect the distribution of arylsulfatase. A, alpha-mannosidase or beta-glucuronidase. The elevated accumulation of 35SO4 by I-cell, Hunter and Maroteaux-Lamy fibroblasts was decreased by the addition of (+)--cyanidanol to the culture medium, but the degradation of previously labeled, intracellular glycosaminoglycans was not. It is concluded that (+)--cyanidanol does not produce a biochemical correction of the enzymic abnormalities existing in I-cell fibroblasts."}
{"id": "PMID:20674", "title": "Structure-activity relationships of some selected beta-adrenergic blocking agents--oxidation with N-bromosuccinimide.", "content": "A relationship between in vitro rate of oxidation by N-bromosuccinimide (NBS) and the pharmacologic activity (pA2) of different beta-adrenergic blockers for different blocking agent-tissue combinations has been studied. The rates of oxidation of the alcoholic group in the drugs by NBS, as well as their molecular conformations as represented by molecular models, were studied in order to determine requirements for selectivity and potency of action of beta-adrenergic blocking agents. Using data from all 7 drugs studied--both nonselective and selective blocking agents--no significant correlation between pA2 and -log k2 (k2 is the second order rate constant for the oxidative reaction) was found. If data from only the 4 nonselective agents were used (16 drug-tissue combinations), a correlation significant at p less than 0.01 was found. Hypotheses are presented to account for the selective action of some beta-adrenergic blocking agents.", "contents": "Structure-activity relationships of some selected beta-adrenergic blocking agents--oxidation with N-bromosuccinimide. A relationship between in vitro rate of oxidation by N-bromosuccinimide (NBS) and the pharmacologic activity (pA2) of different beta-adrenergic blockers for different blocking agent-tissue combinations has been studied. The rates of oxidation of the alcoholic group in the drugs by NBS, as well as their molecular conformations as represented by molecular models, were studied in order to determine requirements for selectivity and potency of action of beta-adrenergic blocking agents. Using data from all 7 drugs studied--both nonselective and selective blocking agents--no significant correlation between pA2 and -log k2 (k2 is the second order rate constant for the oxidative reaction) was found. If data from only the 4 nonselective agents were used (16 drug-tissue combinations), a correlation significant at p less than 0.01 was found. Hypotheses are presented to account for the selective action of some beta-adrenergic blocking agents."}
{"id": "PMID:20678", "title": "Fine structural localization of phosphatases in cilia and basal bodies of Tetrahymena pyriformis.", "content": "Cytochemical localization of ATPase activities in cilia and basal bodies of Tetrahymena pyriformis revealed a number of possible sites of ATPases. In basal bodies, reaction product was localized on the periphery of basal body microtubules, in the core of the B-microtubules, on the dense basal body core, and on the basal plate; some reaction product was associated with the postciliary and basal microtubules. In the cilium, reaction product was associated with the ciliary membrane, the basal granule, the periphery of the outer doublet microtubules, in the core of the B-microtubules, and on the arms and either the central microtubules or the radial spoke heads. Reaction product deposition required ATP and either Ca2+ or Mg2+ or ADP and Mg2+. When incubated in the presence of ATP and Na+, reaction product was only found at the base of the cilium in the region of the ciliary necklace. Implications of the various sites of activity are discussed with respect to possible mechanisms of ciliary motility.", "contents": "Fine structural localization of phosphatases in cilia and basal bodies of Tetrahymena pyriformis. Cytochemical localization of ATPase activities in cilia and basal bodies of Tetrahymena pyriformis revealed a number of possible sites of ATPases. In basal bodies, reaction product was localized on the periphery of basal body microtubules, in the core of the B-microtubules, on the dense basal body core, and on the basal plate; some reaction product was associated with the postciliary and basal microtubules. In the cilium, reaction product was associated with the ciliary membrane, the basal granule, the periphery of the outer doublet microtubules, in the core of the B-microtubules, and on the arms and either the central microtubules or the radial spoke heads. Reaction product deposition required ATP and either Ca2+ or Mg2+ or ADP and Mg2+. When incubated in the presence of ATP and Na+, reaction product was only found at the base of the cilium in the region of the ciliary necklace. Implications of the various sites of activity are discussed with respect to possible mechanisms of ciliary motility."}
{"id": "PMID:20683", "title": "Treatment of detrusor hyperreflexia in multiple sclerosis: a double-blind, crossover clinical trial comparing methantheline bromide (Banthine), flavoxate chloride (Urispas) and meladrazine tartrate (Lisidonil).", "content": "34 patients suffering from detrusor hyperreflexia due to multiple sclerosis entered the trial and 32 patients accomplished. The patients received each drug for a period of 14 days. The patients made records of relevant symptoms, urgency and urge incontinence and compared the treatment periods according to these symptoms. Registration of the number of micturitions was also made. Furthermore, the patients underwent cystometric studies. The following parameters were recorded and compared: residual urine, volume at the first bladder contraction, effective volume and amplitude of the first bladder contraction. The study showed that the patients preferred methantheline bromide. The entire cystometric pattern changed statistically significant with methantheline bromide, but only with concordance to the patients preferences in 60%. Decrease in number of micturitions and volume at the first bladder contraction were the only parameters showing accordance with the preferences. The drugs caused many various side effects. 12 treatment periods were discontinued due to side effects of meladrazine tartrate. The cystometric recordings seem to be of little use in evaluation of a drugs therapeutic effect, and it is difficult to find parameters which reflect the patients preference of the drugs.", "contents": "Treatment of detrusor hyperreflexia in multiple sclerosis: a double-blind, crossover clinical trial comparing methantheline bromide (Banthine), flavoxate chloride (Urispas) and meladrazine tartrate (Lisidonil). 34 patients suffering from detrusor hyperreflexia due to multiple sclerosis entered the trial and 32 patients accomplished. The patients received each drug for a period of 14 days. The patients made records of relevant symptoms, urgency and urge incontinence and compared the treatment periods according to these symptoms. Registration of the number of micturitions was also made. Furthermore, the patients underwent cystometric studies. The following parameters were recorded and compared: residual urine, volume at the first bladder contraction, effective volume and amplitude of the first bladder contraction. The study showed that the patients preferred methantheline bromide. The entire cystometric pattern changed statistically significant with methantheline bromide, but only with concordance to the patients preferences in 60%. Decrease in number of micturitions and volume at the first bladder contraction were the only parameters showing accordance with the preferences. The drugs caused many various side effects. 12 treatment periods were discontinued due to side effects of meladrazine tartrate. The cystometric recordings seem to be of little use in evaluation of a drugs therapeutic effect, and it is difficult to find parameters which reflect the patients preference of the drugs."}
{"id": "PMID:20684", "title": "[Urologic symptoms in the abdominal muscle deficiency syndrome (author's transl)].", "content": "The abdominal muscle deficiency syndrome (\"prune belly syndrome\"(, a symptom triad of aplasia of the abdominal wall musculature, malformations of the urinary tract, and cryptorchism, is described from the urologist's point of view, citing nine cases. With modern diagnostic procedures the early detection of the correct diagnosis in the usually very young patients is possible. While the urologic symptomatology is due to the malformations in the urinary tract, the life expectancy depends mainly on the degree of renal function impairment. Combat of infection together with proper operative repairs are the treatments of choice to date. Instrumental procedures should be limited as much as possible. The survival changes following kidney transplantation appear promising.", "contents": "[Urologic symptoms in the abdominal muscle deficiency syndrome (author's transl)]. The abdominal muscle deficiency syndrome (\"prune belly syndrome\"(, a symptom triad of aplasia of the abdominal wall musculature, malformations of the urinary tract, and cryptorchism, is described from the urologist's point of view, citing nine cases. With modern diagnostic procedures the early detection of the correct diagnosis in the usually very young patients is possible. While the urologic symptomatology is due to the malformations in the urinary tract, the life expectancy depends mainly on the degree of renal function impairment. Combat of infection together with proper operative repairs are the treatments of choice to date. Instrumental procedures should be limited as much as possible. The survival changes following kidney transplantation appear promising."}
{"id": "PMID:20686", "title": "Platelet adhesion to foreign surfaces under controlled conditions of whole blood flow: human vs rabbit, dog, calf, sheep, pig, macaque, and baboon.", "content": "Our results reveal significant differences between mammalian species with respect to platelet adhesion to foreign surfaces exposed to heparinized, flowing blood. In particular, we have demonstrated the following: 1) At a surface shear rate characteristic of shear rates in mammalian arteries, human platelet adhesion (and that of calf, baboon, macaque, hog or sheep) is negligible in comparison to dog or rabbit platelet adhesion after 10 mins of blood flow. 2) The species differences are biomaterial dependent: the human-dog difference is present with Cuprophan or Avcothane, but absent with compressed Gore-Tex or fluorinated ethylcellulose. (The platelets of humans and dogs adhere to comparable degrees on the latter 2 biomaterials.) 3) With Cuprophan and recirculated blood, the human-dog difference persists at 30 and 180 mins. 4) By means of videomicroscopy, the species differences are unlikely only to be an artifact of the possible formation and embolization of surface-adherent aggregates. Tests for the thromboresistance of candidate biomaterials and for platelet adhesion under controlled flow conditions must therefore begin to take into account differences between humans and other species.", "contents": "Platelet adhesion to foreign surfaces under controlled conditions of whole blood flow: human vs rabbit, dog, calf, sheep, pig, macaque, and baboon. Our results reveal significant differences between mammalian species with respect to platelet adhesion to foreign surfaces exposed to heparinized, flowing blood. In particular, we have demonstrated the following: 1) At a surface shear rate characteristic of shear rates in mammalian arteries, human platelet adhesion (and that of calf, baboon, macaque, hog or sheep) is negligible in comparison to dog or rabbit platelet adhesion after 10 mins of blood flow. 2) The species differences are biomaterial dependent: the human-dog difference is present with Cuprophan or Avcothane, but absent with compressed Gore-Tex or fluorinated ethylcellulose. (The platelets of humans and dogs adhere to comparable degrees on the latter 2 biomaterials.) 3) With Cuprophan and recirculated blood, the human-dog difference persists at 30 and 180 mins. 4) By means of videomicroscopy, the species differences are unlikely only to be an artifact of the possible formation and embolization of surface-adherent aggregates. Tests for the thromboresistance of candidate biomaterials and for platelet adhesion under controlled flow conditions must therefore begin to take into account differences between humans and other species."}
{"id": "PMID:20693", "title": "[Characteristics of the ecology of the eastern equine encephalomyelitis virus in the Republic of Cuba].", "content": "Virologic and serological surveys of wild vertebrates carried out in various provinces of Cuba demonstrated definitely that birds were the main hosts of eastern equine encephalomyelitis (EEE) virus in this territory. Fifteen strains of this virus were isolated from 8 species of birds belonging to 5 orders. Isolation of EEE virus from the blood of the endemic genus of iguanas indicates a certain role of cold-blooded animals in the ecology of this agent. Active EEE virus foci have been found in 4 provinces of the Republic of Cuba: Pinar del Rio, Havana, Matanzas and Las Villas. Isolation of a number of EEE virus strains from sick horses during an epizootic in the latter province confirmed the importance role of this agent in the infectious pathology of domestic animals in Cuba. The experimental results suggest that in Cuba there occur at least two types of foci of this infection: forest and water-littoral (fresh-water swamps and lakes, and sea coast with mangrove forests).", "contents": "[Characteristics of the ecology of the eastern equine encephalomyelitis virus in the Republic of Cuba]. Virologic and serological surveys of wild vertebrates carried out in various provinces of Cuba demonstrated definitely that birds were the main hosts of eastern equine encephalomyelitis (EEE) virus in this territory. Fifteen strains of this virus were isolated from 8 species of birds belonging to 5 orders. Isolation of EEE virus from the blood of the endemic genus of iguanas indicates a certain role of cold-blooded animals in the ecology of this agent. Active EEE virus foci have been found in 4 provinces of the Republic of Cuba: Pinar del Rio, Havana, Matanzas and Las Villas. Isolation of a number of EEE virus strains from sick horses during an epizootic in the latter province confirmed the importance role of this agent in the infectious pathology of domestic animals in Cuba. The experimental results suggest that in Cuba there occur at least two types of foci of this infection: forest and water-littoral (fresh-water swamps and lakes, and sea coast with mangrove forests)."}
{"id": "PMID:20692", "title": "[Inhibiting action of glycomacropeptide on stomach secretion induced by various humoral stimulants].", "content": "Tests staged on dogs demonstrated the action of GMP to differ depending upon the nature of the gastric secretion stimulant actually used. The inhibition of the gastric juice secretion occurring against the background of multiple introduction of histamine or gastrin tetrapeptide amide was quite spectacular: the secretion dropped down to zero and the action was more prolonged than following administration of pentagastrin with which the secretion was not inhibited to such a sharp degree and the effect of GMP was less protracted. The mechanism of the GMP action of the gastric secretion and the causes of described differences require further investigations.", "contents": "[Inhibiting action of glycomacropeptide on stomach secretion induced by various humoral stimulants]. Tests staged on dogs demonstrated the action of GMP to differ depending upon the nature of the gastric secretion stimulant actually used. The inhibition of the gastric juice secretion occurring against the background of multiple introduction of histamine or gastrin tetrapeptide amide was quite spectacular: the secretion dropped down to zero and the action was more prolonged than following administration of pentagastrin with which the secretion was not inhibited to such a sharp degree and the effect of GMP was less protracted. The mechanism of the GMP action of the gastric secretion and the causes of described differences require further investigations."}
{"id": "PMID:20699", "title": "[The acid-alkaline equilibrium of the organism and the age (author's transl)].", "content": "In 90 patients (three aging groups: from 20 to 29 years, from 60 to 69 years, from 80 to 89 years) with a physiologic aged status are investigated parameters of acid-alkaline equilibrium. There are no essential aging changes of the blood pH and other parameters, which characterize the acid-alkaline balance of the organism. The investigations in rats show, that with increasing age the possibilities of reserve of regulating mechanism in relation to the acid-alkaline equilibrium decrease.", "contents": "[The acid-alkaline equilibrium of the organism and the age (author's transl)]. In 90 patients (three aging groups: from 20 to 29 years, from 60 to 69 years, from 80 to 89 years) with a physiologic aged status are investigated parameters of acid-alkaline equilibrium. There are no essential aging changes of the blood pH and other parameters, which characterize the acid-alkaline balance of the organism. The investigations in rats show, that with increasing age the possibilities of reserve of regulating mechanism in relation to the acid-alkaline equilibrium decrease."}
{"id": "PMID:20700", "title": "[The water-electrolyte-change and the age (author's transl)].", "content": "In 403 healthy probands between 20 and 103 years old the ionogram of the erythrocytes and of the plasma was analysed. In the one part of the test persons (75 probands) also the water spaces of the organism was examinated. It was established, that the electrolyte composing of the blood is changing with increasing age. In the erythrocytes the content of potassium, magnesium decreases, the content of sodium and chloride increases; in the blood plasma the content of potassium, calcium, magnesium and acid carbonates decreases, the content of acid radical groups--sulphates, phosphates, chlorides and organic acid increases. In an examination of the water spaces was an age depended decreasing of the quantity of total and of the intracellular fluid remarked. The changes probably show the state of the metabolic processes in the age, which is characterized by decreasing of the total metabolism and decreasing of insufficient oxydised products.", "contents": "[The water-electrolyte-change and the age (author's transl)]. In 403 healthy probands between 20 and 103 years old the ionogram of the erythrocytes and of the plasma was analysed. In the one part of the test persons (75 probands) also the water spaces of the organism was examinated. It was established, that the electrolyte composing of the blood is changing with increasing age. In the erythrocytes the content of potassium, magnesium decreases, the content of sodium and chloride increases; in the blood plasma the content of potassium, calcium, magnesium and acid carbonates decreases, the content of acid radical groups--sulphates, phosphates, chlorides and organic acid increases. In an examination of the water spaces was an age depended decreasing of the quantity of total and of the intracellular fluid remarked. The changes probably show the state of the metabolic processes in the age, which is characterized by decreasing of the total metabolism and decreasing of insufficient oxydised products."}
{"id": "PMID:20703", "title": "[The proximal gastric vagotomy in the treatment of uncomplicated duodenal ulcer (author's transl)].", "content": "Of 97 patients, who had a PGV since July 1971, 86 were checked intraoperatively on completeness of vagotomy with various methods, including Kongo-red-staining, pH-electrode and Burge-test. On theoretical grounds, the Burge-test combined with pH-measurement seems the most reliable procedure. In 14 cases an incomplete Vagotomy could such be avoided. 72 patients, who met the critiria of more than 6 months follow-up, were graded according to VISICK with 89% good results (I, II) and 11% VISICK III, IV. Two Patients needed reoperation, one with recurrent ulcer. Our results confirm the good impression we had initially, regarding the low postoperative morbidity, effective reduction of acidity and recurrence rate, but longterm follow-up studies are still required to form a final judgement.", "contents": "[The proximal gastric vagotomy in the treatment of uncomplicated duodenal ulcer (author's transl)]. Of 97 patients, who had a PGV since July 1971, 86 were checked intraoperatively on completeness of vagotomy with various methods, including Kongo-red-staining, pH-electrode and Burge-test. On theoretical grounds, the Burge-test combined with pH-measurement seems the most reliable procedure. In 14 cases an incomplete Vagotomy could such be avoided. 72 patients, who met the critiria of more than 6 months follow-up, were graded according to VISICK with 89% good results (I, II) and 11% VISICK III, IV. Two Patients needed reoperation, one with recurrent ulcer. Our results confirm the good impression we had initially, regarding the low postoperative morbidity, effective reduction of acidity and recurrence rate, but longterm follow-up studies are still required to form a final judgement."}
{"id": "PMID:20708", "title": "The assay of protein-bound nitrite in meat products.", "content": "An improved procedure for the determination of protein-bound nitrite (PBN) in meat products, based on Mirna's method, is described. The results obtained with this modification are significantly higher, and have a lower variation coefficient, than those provided by the old procedure. This is demonstrated by comparison of the analytical results.", "contents": "The assay of protein-bound nitrite in meat products. An improved procedure for the determination of protein-bound nitrite (PBN) in meat products, based on Mirna's method, is described. The results obtained with this modification are significantly higher, and have a lower variation coefficient, than those provided by the old procedure. This is demonstrated by comparison of the analytical results."}
{"id": "PMID:20709", "title": "[Studies on the growth of the width in seminiferous tubules of eutopic and congenitally dystopic testes in children and adolescents].", "content": "The average diameter of the seminiferous tubules is to be regarded as a criterion for the estimation of the morphological value of testicles. By means of 89 autoptically got preparations of regularly descended testicles the breadth-growth of the tubules depending on age in children was judged. Of 55 untreated congenital dystopic testicles morphometric determinations of the diameters of the seminiferous tubules were performed. At the same time 79 unilaterally and 78 bilaterally operatively dislocated, congenital dystopic testicles and 78 contralateral eutopic gonades were evaluated. The average diameter of the tubule of untreated dystopic testicles is significantly (p less than 0.001) smaller than the diameter of the orthotopic gonades corresponding to age. The average diameter of the tubule of operatively dislocated congenital dystopic testicles is, however, larger than the diameter of the untreated gonades corresponding to age. The earlier the treatment of congenital dystopic testicles is performed the larger are the chances of a development of the tubules corresponding to age.", "contents": "[Studies on the growth of the width in seminiferous tubules of eutopic and congenitally dystopic testes in children and adolescents]. The average diameter of the seminiferous tubules is to be regarded as a criterion for the estimation of the morphological value of testicles. By means of 89 autoptically got preparations of regularly descended testicles the breadth-growth of the tubules depending on age in children was judged. Of 55 untreated congenital dystopic testicles morphometric determinations of the diameters of the seminiferous tubules were performed. At the same time 79 unilaterally and 78 bilaterally operatively dislocated, congenital dystopic testicles and 78 contralateral eutopic gonades were evaluated. The average diameter of the tubule of untreated dystopic testicles is significantly (p less than 0.001) smaller than the diameter of the orthotopic gonades corresponding to age. The average diameter of the tubule of operatively dislocated congenital dystopic testicles is, however, larger than the diameter of the untreated gonades corresponding to age. The earlier the treatment of congenital dystopic testicles is performed the larger are the chances of a development of the tubules corresponding to age."}
{"id": "PMID:20710", "title": "[Length-growth of seminiferous tubules of untreated and as surgically displaced, congenitallydystopic testes in children and adolescents].", "content": "The total length of the seminiferous tubules of congenital dystopic testicles was calculated from bioptical preparations. 55 untreated testicles, 79 unilaterally and 78 bilaterally operatively displaced testicles as well as 78 contralaterally eutopic testicles were evaluated. During the whole prepuberal phase of life in the congenital dystopic testicles a nearly continuous growth of the length of the seminiferous tubules takes place. The total length of the intrascrotally displaced testicles is larger than the length of untreated testicles corresponding to age. After the operative correction of the position of congenital dystopic testicles an acceleration of the growth of the length of the tubule begins.", "contents": "[Length-growth of seminiferous tubules of untreated and as surgically displaced, congenitallydystopic testes in children and adolescents]. The total length of the seminiferous tubules of congenital dystopic testicles was calculated from bioptical preparations. 55 untreated testicles, 79 unilaterally and 78 bilaterally operatively displaced testicles as well as 78 contralaterally eutopic testicles were evaluated. During the whole prepuberal phase of life in the congenital dystopic testicles a nearly continuous growth of the length of the seminiferous tubules takes place. The total length of the intrascrotally displaced testicles is larger than the length of untreated testicles corresponding to age. After the operative correction of the position of congenital dystopic testicles an acceleration of the growth of the length of the tubule begins."}
{"id": "PMID:20705", "title": "Gamma-radiolysis of aqueous solution of histidine.", "content": "The dependence of Gi(-M) values of histidine on the concentration of irradiated 10(-4) - 10(-1)M solutions, pH and the presence of O2, N2O and sec-butyl alcohol was investigated. In oxygen-free medium the maximum radiation sensitivity of histidine was found at pH 5--8; in oxygenated solutions it was shifted to the 6--1 pH range. The formation of radiation products was also studied. The course of radiation decomposition of histidine depends on the presence of oxygen and on the pH of irradiated solution.", "contents": "Gamma-radiolysis of aqueous solution of histidine. The dependence of Gi(-M) values of histidine on the concentration of irradiated 10(-4) - 10(-1)M solutions, pH and the presence of O2, N2O and sec-butyl alcohol was investigated. In oxygen-free medium the maximum radiation sensitivity of histidine was found at pH 5--8; in oxygenated solutions it was shifted to the 6--1 pH range. The formation of radiation products was also studied. The course of radiation decomposition of histidine depends on the presence of oxygen and on the pH of irradiated solution."}
{"id": "PMID:20706", "title": "On the influence of aromatic residues on the interaction of copper (II) with small peptides containing aromatic amino acids: ESR and optical studies.", "content": "The complexation behaviour of Cu(II) with di- and tripeptides containing the aromatic amino acids phenylalanine or typtophan has been investigated at different pH-values and compared with results obtained with di- and triglycine. The results obtained by means of ESR and optical absorption spectroscopy show an influence of the two different aromatic entities on the magnetic and optical parameters. A significant decrease of the g11-value and, concomittantly, an increase of the energy of the d-d transition was measured when an aromatic entity is present in the peptide. A possible explanation for this observation is given.", "contents": "On the influence of aromatic residues on the interaction of copper (II) with small peptides containing aromatic amino acids: ESR and optical studies. The complexation behaviour of Cu(II) with di- and tripeptides containing the aromatic amino acids phenylalanine or typtophan has been investigated at different pH-values and compared with results obtained with di- and triglycine. The results obtained by means of ESR and optical absorption spectroscopy show an influence of the two different aromatic entities on the magnetic and optical parameters. A significant decrease of the g11-value and, concomittantly, an increase of the energy of the d-d transition was measured when an aromatic entity is present in the peptide. A possible explanation for this observation is given."}
{"id": "PMID:20719", "title": "Dehydrogenase activity and microbial population in a red sandy soil amended and unamended with incubation.", "content": "Incubation of single bulk sample of freshly collected red sandy soil in trays showed immediate response to added nutrients both in dehydrogenase activity and bacterial and fungal populations. The prevailing acidic pH might have been responsible for the observed response of fungi as well. Actinomycetes population did not fluctuate. It was therefore suggested that TTC dehydrogenase technique for measuring the biological activity could be applicable to coarse-textured and more open soils. There were indications that fungi contributed to the soil dehydrogenase activity as well.", "contents": "Dehydrogenase activity and microbial population in a red sandy soil amended and unamended with incubation. Incubation of single bulk sample of freshly collected red sandy soil in trays showed immediate response to added nutrients both in dehydrogenase activity and bacterial and fungal populations. The prevailing acidic pH might have been responsible for the observed response of fungi as well. Actinomycetes population did not fluctuate. It was therefore suggested that TTC dehydrogenase technique for measuring the biological activity could be applicable to coarse-textured and more open soils. There were indications that fungi contributed to the soil dehydrogenase activity as well."}
{"id": "PMID:20720", "title": "[Purification of protease from staphylococcus aureus (author's transl)].", "content": "380 (80%) of 475 Staphylococcus aureus cultures isolated from humans, cattle and dogs were proteolytically active either on casein or gelatin or both (table 1). Protease-activity could also be demonstrated in experimental body-cavities of rabbits (fig. 1). The enzyme-activity was estimated with azocasein. Protease from S. aureus, M 135 precipitated from the culture supernatant with ammonium sulfate at 65% saturation (table 2). It was purified by 2 filtrations on Ultrogel AcA 44 (fig. 2,3) and subsequent isoelectric focusing between pH 3.5-7.0 (fig. 4). The purified protease yielded only 1 line in the SDS-polyacrylamidegel-electrophoresis, in the gelatin-polyacrylamidegel-electrophoresis and in the double immuno-diffusion test (fig. 5). Its isoelectric point was at pH 4.6, and its highest proteolytic activity between pH 7.5-8.3. The molecular weight was estimated by SDS-polyacrylamidegel-electrophoresis to be near 29.000. The protease-activity was completely inhibited in the presence of EDTA, partially inhibited by Cu2+ and Zn2+ and increased by Mn2+ (table 3).", "contents": "[Purification of protease from staphylococcus aureus (author's transl)]. 380 (80%) of 475 Staphylococcus aureus cultures isolated from humans, cattle and dogs were proteolytically active either on casein or gelatin or both (table 1). Protease-activity could also be demonstrated in experimental body-cavities of rabbits (fig. 1). The enzyme-activity was estimated with azocasein. Protease from S. aureus, M 135 precipitated from the culture supernatant with ammonium sulfate at 65% saturation (table 2). It was purified by 2 filtrations on Ultrogel AcA 44 (fig. 2,3) and subsequent isoelectric focusing between pH 3.5-7.0 (fig. 4). The purified protease yielded only 1 line in the SDS-polyacrylamidegel-electrophoresis, in the gelatin-polyacrylamidegel-electrophoresis and in the double immuno-diffusion test (fig. 5). Its isoelectric point was at pH 4.6, and its highest proteolytic activity between pH 7.5-8.3. The molecular weight was estimated by SDS-polyacrylamidegel-electrophoresis to be near 29.000. The protease-activity was completely inhibited in the presence of EDTA, partially inhibited by Cu2+ and Zn2+ and increased by Mn2+ (table 3)."}
{"id": "PMID:20721", "title": "[On the determination of chlorine with a polarographic probe. 1st communication: Examination of the physical properties of the new instrument (author's transl)].", "content": "A new chlorine measuring device for the field use in the water plant praxis was tested. The portable instrument supplied with a selectively permeable membrane works basing on the polarographic principle and shall allow an easy and accurate measurement of the \"disinfectingpower\" of a water chlorination. In the 1st note most important possibilities of meter-default as dependence on streamvelocity of water, pH and temperature are described. Furter the phenomenon of hysteresis is demonstrated.", "contents": "[On the determination of chlorine with a polarographic probe. 1st communication: Examination of the physical properties of the new instrument (author's transl)]. A new chlorine measuring device for the field use in the water plant praxis was tested. The portable instrument supplied with a selectively permeable membrane works basing on the polarographic principle and shall allow an easy and accurate measurement of the \"disinfectingpower\" of a water chlorination. In the 1st note most important possibilities of meter-default as dependence on streamvelocity of water, pH and temperature are described. Furter the phenomenon of hysteresis is demonstrated."}
{"id": "PMID:20723", "title": "Local hyperalimentation of experimental granulation tissue.", "content": "The effect of local hyperalimentation on developing granulation tissue was studied in rats. Cylindrical hollow viscose cellulose sponge implants were used subcutaneously as an inductive matrix fro the growth of granulation tissue. In the first, control group the implants were kept untouched while the second, \"sham\" group was treated daily by withdrawing 1 ml of wound fluid from the central dead space of the implant and then injecting the fluid back. In the third, hyperalimentation group the aspirated wound fluid was substituted with a corresponding volume of sterile, nonpyrogenic solution containing a mixture of amino acids (Le-7402 A) and glucose, electrolytes and vitamins (Le-7402 B). Within the first week of tissue growth daily application of these nutritional substances caused a changeover of local tissue from predominantly anaerobic towards more oxidative metabolism. Measurement of nucleic acid and hydroxyproline contents indicated enhanced accumulation of cells and collagen in tissues receiving local hyperalimentation. The results combined with earlier data from our laboratory strongly suggest that several types of wounds, especially those containing a marked dead space or large regenerative area, exist in chronic lack of oxygen and other nutrients. Therefore, the healing process in these wounds can be stimulated, to a certain extent, by exposure to increased oxygen tension and/or by local hyperalimentation.", "contents": "Local hyperalimentation of experimental granulation tissue. The effect of local hyperalimentation on developing granulation tissue was studied in rats. Cylindrical hollow viscose cellulose sponge implants were used subcutaneously as an inductive matrix fro the growth of granulation tissue. In the first, control group the implants were kept untouched while the second, \"sham\" group was treated daily by withdrawing 1 ml of wound fluid from the central dead space of the implant and then injecting the fluid back. In the third, hyperalimentation group the aspirated wound fluid was substituted with a corresponding volume of sterile, nonpyrogenic solution containing a mixture of amino acids (Le-7402 A) and glucose, electrolytes and vitamins (Le-7402 B). Within the first week of tissue growth daily application of these nutritional substances caused a changeover of local tissue from predominantly anaerobic towards more oxidative metabolism. Measurement of nucleic acid and hydroxyproline contents indicated enhanced accumulation of cells and collagen in tissues receiving local hyperalimentation. The results combined with earlier data from our laboratory strongly suggest that several types of wounds, especially those containing a marked dead space or large regenerative area, exist in chronic lack of oxygen and other nutrients. Therefore, the healing process in these wounds can be stimulated, to a certain extent, by exposure to increased oxygen tension and/or by local hyperalimentation."}
{"id": "PMID:20727", "title": "Diazepam and flunitrazepam as induction agents for cardiac surgical operations.", "content": "Diazepam and flunitrazepam were compared in equipotent doses as induction agents for premedicated patients having cardiac surgery. Both drugs caused a significant fall in arterial blood pressure, a rise in Paco2 and a fall in Pao2. There was no significant difference between the two drugs in onset time of anaesthesia, cardiovascular or respiratory depression, or quality of induction. There was also no significant difference from induction with thiopentone in these respects. Diazepam, over a 0.2 to 0.6 mg/kg range of doses showed no difference in toxicity, although induction was clinically smoother with the higher dose.", "contents": "Diazepam and flunitrazepam as induction agents for cardiac surgical operations. Diazepam and flunitrazepam were compared in equipotent doses as induction agents for premedicated patients having cardiac surgery. Both drugs caused a significant fall in arterial blood pressure, a rise in Paco2 and a fall in Pao2. There was no significant difference between the two drugs in onset time of anaesthesia, cardiovascular or respiratory depression, or quality of induction. There was also no significant difference from induction with thiopentone in these respects. Diazepam, over a 0.2 to 0.6 mg/kg range of doses showed no difference in toxicity, although induction was clinically smoother with the higher dose."}
{"id": "PMID:20728", "title": "The effects of PaCO2 reduction on regional cerebral blood flow in the acute phase of brain injury.", "content": "In 26 unconscious patients with brain injuries, regional cerebral blood flow (rCBF) was measured with a 16-channel Cerebrograph before and after acute reduction of PaCO2. The intra-arterial 133xenon washout technique was used, and CBF was calculated regionally as initial slope index or stochastic flow. The CO2 reactivity was calculated as deltaln CBV/deltaPaCO2. In supratentorial cortical lesions, an acute fall in PaCO2 increased the homogeneity of the regional flow pattern (decrease in the standard deviation of the regional flow values), and reduced the number of focal hyperaemic regions (tissue peaks). The CO2 reactivity in tissue peak regions was generally higher than in regions without tissue peaks. In severely injured patients with a poor outcome (dementia, vegetative survival or death), inverse steal reaction was accounted for in 11% of all regions, but only in 3% of the regions in patients who survived without dementia. Inverse steal reaction was most frequently seen during the first 3 days after the trauma. In repeated CBF studies, an increase in the CO2 reactivity with time was observed after the acute trauma. In comparison with the CO2 reactivity found in normocapnic awake subjects, this increase was higher than expected in several cases.", "contents": "The effects of PaCO2 reduction on regional cerebral blood flow in the acute phase of brain injury. In 26 unconscious patients with brain injuries, regional cerebral blood flow (rCBF) was measured with a 16-channel Cerebrograph before and after acute reduction of PaCO2. The intra-arterial 133xenon washout technique was used, and CBF was calculated regionally as initial slope index or stochastic flow. The CO2 reactivity was calculated as deltaln CBV/deltaPaCO2. In supratentorial cortical lesions, an acute fall in PaCO2 increased the homogeneity of the regional flow pattern (decrease in the standard deviation of the regional flow values), and reduced the number of focal hyperaemic regions (tissue peaks). The CO2 reactivity in tissue peak regions was generally higher than in regions without tissue peaks. In severely injured patients with a poor outcome (dementia, vegetative survival or death), inverse steal reaction was accounted for in 11% of all regions, but only in 3% of the regions in patients who survived without dementia. Inverse steal reaction was most frequently seen during the first 3 days after the trauma. In repeated CBF studies, an increase in the CO2 reactivity with time was observed after the acute trauma. In comparison with the CO2 reactivity found in normocapnic awake subjects, this increase was higher than expected in several cases."}
{"id": "PMID:20729", "title": "Parkinsonian tremor: a neuropharmacological study.", "content": "In the Parkinsonian syndrome tremor is the symptom which still eludes pharmacological therapy. The authors report the results of nine cases of Parkinsonian tremor in which agonist and antagonist drugs acting on the receptors were employed. These were dopaminergics, acetylcholinergics, serotoninergics, histaminics, and alpha- and beta-adrenergics. The data obtained demonstrate the involvement of all the neurotransmitters studied, some directly through quantitative modifications, others indirectly through their involvement in reciprocal functional equilibria. A sytem of equilibria is hypothesized in which the histamine: serotonin ratio is given greater emphasis. (Acta neurol belg., 1977, 77, 213-229).", "contents": "Parkinsonian tremor: a neuropharmacological study. In the Parkinsonian syndrome tremor is the symptom which still eludes pharmacological therapy. The authors report the results of nine cases of Parkinsonian tremor in which agonist and antagonist drugs acting on the receptors were employed. These were dopaminergics, acetylcholinergics, serotoninergics, histaminics, and alpha- and beta-adrenergics. The data obtained demonstrate the involvement of all the neurotransmitters studied, some directly through quantitative modifications, others indirectly through their involvement in reciprocal functional equilibria. A sytem of equilibria is hypothesized in which the histamine: serotonin ratio is given greater emphasis. (Acta neurol belg., 1977, 77, 213-229)."}
{"id": "PMID:20736", "title": "Evidence of decarboxylation of lysine by mammalian ornithine decarboxylase.", "content": "In enzymic preparations from mouse kidney stimulated with the anabolic steroid Durabolin (nandrolone phenpropionate) lysine and ornithine were shown to inhibit the decarboxylation of each other competitively. The Michaelis constants for the decarboxylations were approximately equal to the inhibition constants of the two amino acids. The pH optima of the decarboxylation of lysine and ornithine were found to be identical. Chromatographic studies of the enzyme preparation on a Sephadex G-150 Superfine column did not bring about a separation of the two enzyme activities. The ratio of the decarboxylating activities was practically the same during the elution. Lysine decarboxylating activity was also shown to be present in growth hormone stimulated rat liver. The results are in agreement with the assumption that the decarboxylation of lysine and ornithine is carried out by the same enzyme.", "contents": "Evidence of decarboxylation of lysine by mammalian ornithine decarboxylase. In enzymic preparations from mouse kidney stimulated with the anabolic steroid Durabolin (nandrolone phenpropionate) lysine and ornithine were shown to inhibit the decarboxylation of each other competitively. The Michaelis constants for the decarboxylations were approximately equal to the inhibition constants of the two amino acids. The pH optima of the decarboxylation of lysine and ornithine were found to be identical. Chromatographic studies of the enzyme preparation on a Sephadex G-150 Superfine column did not bring about a separation of the two enzyme activities. The ratio of the decarboxylating activities was practically the same during the elution. Lysine decarboxylating activity was also shown to be present in growth hormone stimulated rat liver. The results are in agreement with the assumption that the decarboxylation of lysine and ornithine is carried out by the same enzyme."}
{"id": "PMID:20741", "title": "New amino acid derivatives formed by alkaline treatment of proteins.", "content": "Intense heat treatment of proteins at high pH favors formation of transient, reactive intermediates derived from serine and cystine. The postulated dehydroalanine intermediate reacts further with the epsilon-amino groups side chains and sulfhydryl groups of cysteine residues to form derivatives of lysinoalanine and lanthionine. Recent studies indicate that besides these crosslinked products, several others are formed, by reaction of histidine, arginine, and possibly other residues. For this reason, caution should be exercised in assigning the prelysine peak(s) of an amino acid chromatogram to lysinoalanine. These results suggest that unnatural amino acid derivatives, other than lysinoalanine, may also contribute to the toxic effects reported from studies in which alkali-treated protein was fed to rats.", "contents": "New amino acid derivatives formed by alkaline treatment of proteins. Intense heat treatment of proteins at high pH favors formation of transient, reactive intermediates derived from serine and cystine. The postulated dehydroalanine intermediate reacts further with the epsilon-amino groups side chains and sulfhydryl groups of cysteine residues to form derivatives of lysinoalanine and lanthionine. Recent studies indicate that besides these crosslinked products, several others are formed, by reaction of histidine, arginine, and possibly other residues. For this reason, caution should be exercised in assigning the prelysine peak(s) of an amino acid chromatogram to lysinoalanine. These results suggest that unnatural amino acid derivatives, other than lysinoalanine, may also contribute to the toxic effects reported from studies in which alkali-treated protein was fed to rats."}
{"id": "PMID:20743", "title": "35S-Sulfide incorporation during alkaline treatment of keratin and its relation to lanthionine formation.", "content": "Cattle hair exposed to solutions of 35S-sulfide ions at pH 12.5, hydrolyzed with acid, and analyzed for amino acids with simultaneous measurement of the radioactivity of the eluate from the analytical column showed 87 percent of the radioactivity incorporated in the hair in three amino acids: cysteic acid, lanthionine, and cystine. This and other evidence presented lend further support to the intermediacy of dehydroalanyl residues formed by a beta-elimination reaction in the conversion of cystinyl residues to lanthionyl residues in proteins. The presence of radioactively labelled cystine in the hydrolyzate indicates that the dehydroalanyl residues are also capable of reforming cystinyl residues under these same conditions through a series of reversible reactions.", "contents": "35S-Sulfide incorporation during alkaline treatment of keratin and its relation to lanthionine formation. Cattle hair exposed to solutions of 35S-sulfide ions at pH 12.5, hydrolyzed with acid, and analyzed for amino acids with simultaneous measurement of the radioactivity of the eluate from the analytical column showed 87 percent of the radioactivity incorporated in the hair in three amino acids: cysteic acid, lanthionine, and cystine. This and other evidence presented lend further support to the intermediacy of dehydroalanyl residues formed by a beta-elimination reaction in the conversion of cystinyl residues to lanthionyl residues in proteins. The presence of radioactively labelled cystine in the hydrolyzate indicates that the dehydroalanyl residues are also capable of reforming cystinyl residues under these same conditions through a series of reversible reactions."}
{"id": "PMID:20738", "title": "Treatment of the \"syndrome of doubles\".", "content": "An account of the response to biological treatment of 20 patients with the syndrome of doubles (syndrome of Capgras, syndrome of Fr\u00e9goli, syndrome of Intermetamorphosis, syndrome of subjective doubles) is presented. Our observations indicate that: a) the syndrome of doubles may respond to various biological treatment methods; b) in the setting of depression it responds to tricyclic antidepressants; c) in the setting of schizophrenia or organic psychosis it usually responds to neurolytics; d) in a schizophrenic setting it has more chances of responding to trifluoperazine either given alone or in association with other psychopharmaca, and, e) in certain cases combination of antipsychotic treatment with treatment of co-existing organic dysfunction appears to be important.", "contents": "Treatment of the \"syndrome of doubles\". An account of the response to biological treatment of 20 patients with the syndrome of doubles (syndrome of Capgras, syndrome of Fr\u00e9goli, syndrome of Intermetamorphosis, syndrome of subjective doubles) is presented. Our observations indicate that: a) the syndrome of doubles may respond to various biological treatment methods; b) in the setting of depression it responds to tricyclic antidepressants; c) in the setting of schizophrenia or organic psychosis it usually responds to neurolytics; d) in a schizophrenic setting it has more chances of responding to trifluoperazine either given alone or in association with other psychopharmaca, and, e) in certain cases combination of antipsychotic treatment with treatment of co-existing organic dysfunction appears to be important."}
{"id": "PMID:20744", "title": "Lysinoalanine formation in wool after treatments with some phosphate salts.", "content": "Treatment of wool with solutions of sodium tripolyphosphate, potassium tetrapyrophosphate, and sodium phosphate results in the formation of lysinoalanine, the amount of which increases from the first to the last reagent. As this may be due to the different pH, solutions of the three salts of the same pH were also tried. This series of experiments suggests that although the hydroxyl ions contribute to the formation of lysinoalanine, the governing factor is the kind of the anions concerned, as the sodium phosphate acts in a more rigorous may than the two other salts, in spite of the smaller concentration and the faster reduction of the pH of the solution during treatment.", "contents": "Lysinoalanine formation in wool after treatments with some phosphate salts. Treatment of wool with solutions of sodium tripolyphosphate, potassium tetrapyrophosphate, and sodium phosphate results in the formation of lysinoalanine, the amount of which increases from the first to the last reagent. As this may be due to the different pH, solutions of the three salts of the same pH were also tried. This series of experiments suggests that although the hydroxyl ions contribute to the formation of lysinoalanine, the governing factor is the kind of the anions concerned, as the sodium phosphate acts in a more rigorous may than the two other salts, in spite of the smaller concentration and the faster reduction of the pH of the solution during treatment."}
{"id": "PMID:20745", "title": "The formation and cleavage of lysinoalanine crosslinks.", "content": "Treatment of lysinoalanine (LAL) with methyl iodide at pH-values above 8 leads to cleavage to dehydroalanine (DHA) and Nepsilon-di- or/and trimethyllysine, as was shown by ultraviolet spectra and amino acid analysis. This reaction is due to methylation of the crosslinking NH group of LAL to the quaternary ammonium compound; nucleophilic beta-elimination follows. By this reaction, the epsilon-amino groups of polylysine and its copolymers can be methylated to form di- and/or trimetryl-lysine residues. Chemically modified polypeptides containing Nepsilon-dimethyllysine can be made in this way.", "contents": "The formation and cleavage of lysinoalanine crosslinks. Treatment of lysinoalanine (LAL) with methyl iodide at pH-values above 8 leads to cleavage to dehydroalanine (DHA) and Nepsilon-di- or/and trimethyllysine, as was shown by ultraviolet spectra and amino acid analysis. This reaction is due to methylation of the crosslinking NH group of LAL to the quaternary ammonium compound; nucleophilic beta-elimination follows. By this reaction, the epsilon-amino groups of polylysine and its copolymers can be methylated to form di- and/or trimetryl-lysine residues. Chemically modified polypeptides containing Nepsilon-dimethyllysine can be made in this way."}
{"id": "PMID:20746", "title": "On the specific cleavage of cysteine containing peptides and proteins.", "content": "Addition of cysteine to the double bonds of polydehydroalanine and copolymers of dehydroalanine (DHA) and methylcysteine, alanine, leucine or gamma- methyl-L-glutamate is accompanied by increased solubility and decreased molecular weight. This result is due to a peptide bond cleavage caused by formation of a thiazolidine as a consequence of nucleophilic attack by the sulfur atom on the preceding C=O group and subsequent splitting of the peptide bond by nucleophilic attack of an OH ion. This mechanism is predominant in alkaline media; in acid another mechanism is favoured; carbonyl-oxygen attacks the carbonyl-C-atom of the cysteine residue, forming a second ring system. Addition of one water molecule then yields two peptide fragments, one of them a terminal cysteine residue. Both mechanisms could be confirmed in the case of gamma-L-glutamyl-dehydroalanyl-glycine by adding cysteine. Furthermore, it could be shown that SH-glutathione is decomposed at alevated temperatures according to the two mechanisms mentioned. This SH-induced peptide bond cleavage can be used for selective peptide chain splitting of cysteine-containing polypeptides and proteins under relatively mild conditions.", "contents": "On the specific cleavage of cysteine containing peptides and proteins. Addition of cysteine to the double bonds of polydehydroalanine and copolymers of dehydroalanine (DHA) and methylcysteine, alanine, leucine or gamma- methyl-L-glutamate is accompanied by increased solubility and decreased molecular weight. This result is due to a peptide bond cleavage caused by formation of a thiazolidine as a consequence of nucleophilic attack by the sulfur atom on the preceding C=O group and subsequent splitting of the peptide bond by nucleophilic attack of an OH ion. This mechanism is predominant in alkaline media; in acid another mechanism is favoured; carbonyl-oxygen attacks the carbonyl-C-atom of the cysteine residue, forming a second ring system. Addition of one water molecule then yields two peptide fragments, one of them a terminal cysteine residue. Both mechanisms could be confirmed in the case of gamma-L-glutamyl-dehydroalanyl-glycine by adding cysteine. Furthermore, it could be shown that SH-glutathione is decomposed at alevated temperatures according to the two mechanisms mentioned. This SH-induced peptide bond cleavage can be used for selective peptide chain splitting of cysteine-containing polypeptides and proteins under relatively mild conditions."}
{"id": "PMID:20747", "title": "Reactions of proteins with dehydroalanines.", "content": "Reactions of proteins with dehydroalanine or derivatives of dehydroalanine were studied as models for protein crosslinking. Treatment of casein, bovine serum albumin, lysozyme, wool or polylysine with acetamido- and phenylacetamido acrylic acid methyl esters at pH 9-10 converted varying amounts of lysine to lysinoalanine residues. Howver, complete transformation was not achieved. Incomplete reaction is atributed to partial hydrolysis of the esters to the less reactive acrylic acids under the reaction conditions. Similar studies were made of the reactivities of protein SH groups generated by reduction of disulfide bonds by tributylphosphine. The SH groups could be completely alkylated at pH 7.6 in aqueous propanol, as shown by nearly quantitative recovery of lanthionine. Such a procedure might therefore be used to estimate cystine contents of proteins.", "contents": "Reactions of proteins with dehydroalanines. Reactions of proteins with dehydroalanine or derivatives of dehydroalanine were studied as models for protein crosslinking. Treatment of casein, bovine serum albumin, lysozyme, wool or polylysine with acetamido- and phenylacetamido acrylic acid methyl esters at pH 9-10 converted varying amounts of lysine to lysinoalanine residues. Howver, complete transformation was not achieved. Incomplete reaction is atributed to partial hydrolysis of the esters to the less reactive acrylic acids under the reaction conditions. Similar studies were made of the reactivities of protein SH groups generated by reduction of disulfide bonds by tributylphosphine. The SH groups could be completely alkylated at pH 7.6 in aqueous propanol, as shown by nearly quantitative recovery of lanthionine. Such a procedure might therefore be used to estimate cystine contents of proteins."}
{"id": "PMID:20748", "title": "The formation, isolation and importance of isopeptides in heated proteins.", "content": "The separation and resolution of the isopeptides Nepsilon (gamma-L-glutamyl)-L-lysine and Nepsilon (beta-aspertyl)-L-lysine, formed in heated proteins, has been successfully achieved. The method demands a well characterised ion-exchange column and the use of pH 3.40 lithium citrate buffer (O.2N Li+). Due to variations in particle size and percentage crosslinkages in the ion-exchange resin a computer assisted buffer gradient system has been developed. This system affects resolution of both isopeptides in 7h. The use of leucyl-glycine as an internal standard facilitates quantitative estimation of the isopeptides. This separative method has been used to analyse a series of heated protein samples and to estimate the quantities of isopeptides formed. The ability of a protein to form isopeptides links is discussed as well as the implication of such links on the reactivity and digestibility of proteins.", "contents": "The formation, isolation and importance of isopeptides in heated proteins. The separation and resolution of the isopeptides Nepsilon (gamma-L-glutamyl)-L-lysine and Nepsilon (beta-aspertyl)-L-lysine, formed in heated proteins, has been successfully achieved. The method demands a well characterised ion-exchange column and the use of pH 3.40 lithium citrate buffer (O.2N Li+). Due to variations in particle size and percentage crosslinkages in the ion-exchange resin a computer assisted buffer gradient system has been developed. This system affects resolution of both isopeptides in 7h. The use of leucyl-glycine as an internal standard facilitates quantitative estimation of the isopeptides. This separative method has been used to analyse a series of heated protein samples and to estimate the quantities of isopeptides formed. The ability of a protein to form isopeptides links is discussed as well as the implication of such links on the reactivity and digestibility of proteins."}
{"id": "PMID:20749", "title": "Cross-linking of protein by peroxidase.", "content": "The reaction products of peroxidase, a hydrogen donor and hydrogen peroxide decreased the amount of lysine recovered from proteins after acid hydrolysis. Oxidation of peroxidase treated proteins with performic acid prior to hydrolysis formed alpha-amino adipic acid indicating that the peroxidase or the quinones formed by peroxidase had oxidatively deaminated some lysyl residues of the protein to form lysyl aldehyde. Gel filtration and polyacrylamide gel electrophoresis revealed dimers, trimers and higher protein polymers that were not detected when peroxidase was omitted. Since some of the protein polymers were not dissociated by gel electrophoresis in the presence of dodecyl sulfate, urea and mercaptoethanol, it suggests that the free radicals or quinones formed by peroxidase had interacted with or cross-linked protein molecules by the formation of covalent bonds. Oxidative enzymes like peroxidase and polyphenol oxidase may lower the nutritive value of proteins by the oxidative deamination of lysine, reaction with cysteine and methionine and by cross-linking protein molecules to reduce their susceptibility to enzymatic hydrolysis.", "contents": "Cross-linking of protein by peroxidase. The reaction products of peroxidase, a hydrogen donor and hydrogen peroxide decreased the amount of lysine recovered from proteins after acid hydrolysis. Oxidation of peroxidase treated proteins with performic acid prior to hydrolysis formed alpha-amino adipic acid indicating that the peroxidase or the quinones formed by peroxidase had oxidatively deaminated some lysyl residues of the protein to form lysyl aldehyde. Gel filtration and polyacrylamide gel electrophoresis revealed dimers, trimers and higher protein polymers that were not detected when peroxidase was omitted. Since some of the protein polymers were not dissociated by gel electrophoresis in the presence of dodecyl sulfate, urea and mercaptoethanol, it suggests that the free radicals or quinones formed by peroxidase had interacted with or cross-linked protein molecules by the formation of covalent bonds. Oxidative enzymes like peroxidase and polyphenol oxidase may lower the nutritive value of proteins by the oxidative deamination of lysine, reaction with cysteine and methionine and by cross-linking protein molecules to reduce their susceptibility to enzymatic hydrolysis."}
{"id": "PMID:20750", "title": "Biological effects of alkali-treated protein and lysinoalanine: an overview.", "content": "The renal alterations induced by alkali-treated protein and lysinoalanine are reviewed and their biological implications discussed. Alkali-treated proteins and lysinoalanine, an unusual amino acid formed in proteins during alkali treatment, have been shown to produce a renal alteration characterized by nuclear and cytoplasmic enlargement, with alterations in DNA synthesis, mitotsis and nucleoprotein. These changes are localized in the straight portion of the proximal renal tubule and have been observed in rats but not in several other species. The nephrotoxic effect of synthetic lysinoalanine has been consistently demonstrated, but the ability of alkali-treated protein to induce renal alterations is apparently modified by factors other than lysinoalanine content. Factors which may influence the development of the kidney lesions in animals fed alkali-treatment protein are discussed, including nutritional factors, the chemical form of lysinoalanine in the protein, species differences, and metabolic fate. Other clinical and experimental conditions that result in similar renal alterations are presented for comparison with the lysinoalanine induced lesion, and possible functional consequences are considred.", "contents": "Biological effects of alkali-treated protein and lysinoalanine: an overview. The renal alterations induced by alkali-treated protein and lysinoalanine are reviewed and their biological implications discussed. Alkali-treated proteins and lysinoalanine, an unusual amino acid formed in proteins during alkali treatment, have been shown to produce a renal alteration characterized by nuclear and cytoplasmic enlargement, with alterations in DNA synthesis, mitotsis and nucleoprotein. These changes are localized in the straight portion of the proximal renal tubule and have been observed in rats but not in several other species. The nephrotoxic effect of synthetic lysinoalanine has been consistently demonstrated, but the ability of alkali-treated protein to induce renal alterations is apparently modified by factors other than lysinoalanine content. Factors which may influence the development of the kidney lesions in animals fed alkali-treatment protein are discussed, including nutritional factors, the chemical form of lysinoalanine in the protein, species differences, and metabolic fate. Other clinical and experimental conditions that result in similar renal alterations are presented for comparison with the lysinoalanine induced lesion, and possible functional consequences are considred."}
{"id": "PMID:20752", "title": "Some chemical and nutritional properties of feather protein isolates containing varying half-cystine levels.", "content": "Feather (keratinous) protein isolates containing 2.8 and 7.2% half-cystine were prepared. Solubility of the former increased to 100% between pH 6 and 12, whereas, that of the latter reached only 2.5% at pH 12. Tests showed that mixtures of sodium dodecyl sulfate and 2-mercaptoethanol were needed to completely solubilize the high half-cystine protein, and that sodium dodecyl sulfate alone or in combination with urea and/or 2-mercaptoethanol increased solubilization of the low half-cystine product. The rates of these reactions are further increased by heat. Dry heat denatured the  low half-cystine isolate more readily than the high half-cystine product; moist heat denatured both at a similar rate. Gel electrophoretic properties were unique for each keratinous product. Only the low half-cystine isolate ahd desirable functional properties in that it formed thick, viscous mayonnaise-like emulsions and desirable foams. Functional properties of this isolate were improved dramatically by adjusting the pH from 5.0 to 8.2 or by a two-step change from pH 5.0 to 4.0 to 8.2. Apparent nitrogen digestibility of the two keratinous isolates was greater than 90% as measured by rat growth and by pepsin-HCl digestion.", "contents": "Some chemical and nutritional properties of feather protein isolates containing varying half-cystine levels. Feather (keratinous) protein isolates containing 2.8 and 7.2% half-cystine were prepared. Solubility of the former increased to 100% between pH 6 and 12, whereas, that of the latter reached only 2.5% at pH 12. Tests showed that mixtures of sodium dodecyl sulfate and 2-mercaptoethanol were needed to completely solubilize the high half-cystine protein, and that sodium dodecyl sulfate alone or in combination with urea and/or 2-mercaptoethanol increased solubilization of the low half-cystine product. The rates of these reactions are further increased by heat. Dry heat denatured the  low half-cystine isolate more readily than the high half-cystine product; moist heat denatured both at a similar rate. Gel electrophoretic properties were unique for each keratinous product. Only the low half-cystine isolate ahd desirable functional properties in that it formed thick, viscous mayonnaise-like emulsions and desirable foams. Functional properties of this isolate were improved dramatically by adjusting the pH from 5.0 to 8.2 or by a two-step change from pH 5.0 to 4.0 to 8.2. Apparent nitrogen digestibility of the two keratinous isolates was greater than 90% as measured by rat growth and by pepsin-HCl digestion."}
{"id": "PMID:20754", "title": "Protected proteins in ruminant nutrition. In vitro evaluation of casein derivatives.", "content": "Chemical treatment of proteins in feeds can, by crosslinking protein chains or other chemical effects, decrease their solubility and microbial degradation in the rumen. A need exists to modify proteins systematically under well-defined conditions with inexpensive reagents and to evaluate the treated products nutritionally for possible beneficial effects on wool growth and quality as well as production of meat and milk. As a first step toward this goal we evaluated many derivatives of casein treated at pH 9-10 with various acylating and alkylating agents. Initial tests indicate that all treatments decreased protein digestion by rumen microorganisms. Potentially crosslinking reagents are usually more effective than similar ones that cannot crosslink. A few treatments gave ruminal protection that approached or exceeded that obtained with formaldehyde. This result shows that systematic evaluation of ruminal in vitro digestibility of protein derivatives may disclose new products deserving tests of post-ruminal digestibility and practical nutritive value.", "contents": "Protected proteins in ruminant nutrition. In vitro evaluation of casein derivatives. Chemical treatment of proteins in feeds can, by crosslinking protein chains or other chemical effects, decrease their solubility and microbial degradation in the rumen. A need exists to modify proteins systematically under well-defined conditions with inexpensive reagents and to evaluate the treated products nutritionally for possible beneficial effects on wool growth and quality as well as production of meat and milk. As a first step toward this goal we evaluated many derivatives of casein treated at pH 9-10 with various acylating and alkylating agents. Initial tests indicate that all treatments decreased protein digestion by rumen microorganisms. Potentially crosslinking reagents are usually more effective than similar ones that cannot crosslink. A few treatments gave ruminal protection that approached or exceeded that obtained with formaldehyde. This result shows that systematic evaluation of ruminal in vitro digestibility of protein derivatives may disclose new products deserving tests of post-ruminal digestibility and practical nutritive value."}
{"id": "PMID:20758", "title": "Inhibitory effect of mercaptoamino acids on lysino-alanine formation during alkali treatment of proteins.", "content": "Alkali treatment of food proteins converts some amino acid residues to the unnatural amino acid lysinoalanine which has been found to cause kidney damage when fed to rats. Formation of lysinoalanine was essentially prevented when isolates of soy protein and casein were exposed to alkali in the presence of thio-alamino acids such as cysteine. The results suggest that added thiols minimize the formation of potentially toxic lysinoalanine.", "contents": "Inhibitory effect of mercaptoamino acids on lysino-alanine formation during alkali treatment of proteins. Alkali treatment of food proteins converts some amino acid residues to the unnatural amino acid lysinoalanine which has been found to cause kidney damage when fed to rats. Formation of lysinoalanine was essentially prevented when isolates of soy protein and casein were exposed to alkali in the presence of thio-alamino acids such as cysteine. The results suggest that added thiols minimize the formation of potentially toxic lysinoalanine."}
{"id": "PMID:20761", "title": "Structural proteins of infectious bovine rhinotracheitis virus.", "content": "Infectious bovine rhinotracheitis (IBR) virus grown in bovine embryo kidney cell cultures was concentrated and purified in Ficoll density gradients. The polypeptide composition of the virus was studied by polyacrylamide gel electrophoresis. The mature virion was found to contain 18 structural proteins with molecular weights from 250,000 to 29,000 daltons; 8 of them were glycosylated. The similarity of IBR virus protein composition to proteins of other herpetoviruses is discussed.", "contents": "Structural proteins of infectious bovine rhinotracheitis virus. Infectious bovine rhinotracheitis (IBR) virus grown in bovine embryo kidney cell cultures was concentrated and purified in Ficoll density gradients. The polypeptide composition of the virus was studied by polyacrylamide gel electrophoresis. The mature virion was found to contain 18 structural proteins with molecular weights from 250,000 to 29,000 daltons; 8 of them were glycosylated. The similarity of IBR virus protein composition to proteins of other herpetoviruses is discussed."}
{"id": "PMID:20762", "title": "Investigation on the mechanisms of the failure of human influenza virus to replicate in chick embryo cell cultures.", "content": "Thirteen strains of human influenza virus producing in chick embryo cell (CEC) cultures either virions with low infectivity or no virions were studied. In CEC, most of the strains induced synthesis of viral RNA, polypeptides, and ribonucleoprotein and produced functionaly active haemagglutinin, neuraminidase and virions lower infectivity. The low infectivity of virions produced by strains of this functional group was due to disturbed cleavage of a polypeptide, haemagglutinin precursor, formed in CEC, into a heavy a light haemagglutinin chain. Two strains belonging to another functional group induced no synthesis of virus-specific macromolecules in CEC, but were able to adsorb onto the cells. With one of these viruses, no transcription of parental RNA could be detected in CEC. There was no relationship between the grouping of the studied strains into a certain functional group with their antigenic characteristics, the year of isolation, the passage history in chick embryos and human pathogenicity.", "contents": "Investigation on the mechanisms of the failure of human influenza virus to replicate in chick embryo cell cultures. Thirteen strains of human influenza virus producing in chick embryo cell (CEC) cultures either virions with low infectivity or no virions were studied. In CEC, most of the strains induced synthesis of viral RNA, polypeptides, and ribonucleoprotein and produced functionaly active haemagglutinin, neuraminidase and virions lower infectivity. The low infectivity of virions produced by strains of this functional group was due to disturbed cleavage of a polypeptide, haemagglutinin precursor, formed in CEC, into a heavy a light haemagglutinin chain. Two strains belonging to another functional group induced no synthesis of virus-specific macromolecules in CEC, but were able to adsorb onto the cells. With one of these viruses, no transcription of parental RNA could be detected in CEC. There was no relationship between the grouping of the studied strains into a certain functional group with their antigenic characteristics, the year of isolation, the passage history in chick embryos and human pathogenicity."}
{"id": "PMID:20763", "title": "Suppressive effect of Newcastle disease virus on the primary and secondary immune responses of hamsters.", "content": "The effect of Newcastle disease virus (NDV) on the formation of 19 S haemolytic plaque-forming cells (HPFC) in the secondary immune response and on the formation of 7 S HPFC in both primary and secondary immune responses of hamsters to sheep red blood cells (SRBC) was studied. The 19 S and the 7 S HPFC in the spleens of hamsters injected with SRBC were demonstrated by the direct and indirect Jerne's method, repectively. A single intraperitoneal injection of NDV 5 days prior to primary immunization markedly depressed the number of 7 S HPFC. NDV administered 5 days prior to the second injection of SRBC resulted in a significant decrease in the number of both 19 S and 7 S HPFC. It is asssumed that interferon induced by NDV is responsible for the suppressive effect of the virus on both the primary and secondary immune responses of hamsters to SRBC.", "contents": "Suppressive effect of Newcastle disease virus on the primary and secondary immune responses of hamsters. The effect of Newcastle disease virus (NDV) on the formation of 19 S haemolytic plaque-forming cells (HPFC) in the secondary immune response and on the formation of 7 S HPFC in both primary and secondary immune responses of hamsters to sheep red blood cells (SRBC) was studied. The 19 S and the 7 S HPFC in the spleens of hamsters injected with SRBC were demonstrated by the direct and indirect Jerne's method, repectively. A single intraperitoneal injection of NDV 5 days prior to primary immunization markedly depressed the number of 7 S HPFC. NDV administered 5 days prior to the second injection of SRBC resulted in a significant decrease in the number of both 19 S and 7 S HPFC. It is asssumed that interferon induced by NDV is responsible for the suppressive effect of the virus on both the primary and secondary immune responses of hamsters to SRBC."}
{"id": "PMID:20764", "title": "Concentration and purification of tick-borne encephalitis virus grown in suspensions of chick embryo cells.", "content": "Tick-borne encephalitis (TBE) virus grown in suspensions of chick embryo cells was precipitated by various concentrations of polyethylene glycol (PEG) 6000. Quantitative recovery was obtained at PEG concentrations of 5% and higher. As precipitation of contaminating non-viral protein increases with increasing PEG concentrations, best results with respect to purity and recovery were obtained at 5% PEG 6000. Analysis of virus concentrates by rate zonal centrifugation revealed two peaks--rapidly sedimenting haemagglutinin (RHA) associated with infectivity and slowly sedimenting haemagglutinin (SHA)--characteristic of Flaviviruses. Purification factors after PEG precipitation followed by rate zonal centrifugation in sucrose density gradients ranged from 50 to 200 for HA activity and from 40 to 50 for infectivity.", "contents": "Concentration and purification of tick-borne encephalitis virus grown in suspensions of chick embryo cells. Tick-borne encephalitis (TBE) virus grown in suspensions of chick embryo cells was precipitated by various concentrations of polyethylene glycol (PEG) 6000. Quantitative recovery was obtained at PEG concentrations of 5% and higher. As precipitation of contaminating non-viral protein increases with increasing PEG concentrations, best results with respect to purity and recovery were obtained at 5% PEG 6000. Analysis of virus concentrates by rate zonal centrifugation revealed two peaks--rapidly sedimenting haemagglutinin (RHA) associated with infectivity and slowly sedimenting haemagglutinin (SHA)--characteristic of Flaviviruses. Purification factors after PEG precipitation followed by rate zonal centrifugation in sucrose density gradients ranged from 50 to 200 for HA activity and from 40 to 50 for infectivity."}
{"id": "PMID:20765", "title": "Characterization of tick-borne encephalitis virus and immunogenicity of its surface components in mice.", "content": "Tick-borne encephalitis (TBE) virus grown in chick embryo cells and purified by rate-zonal centrifugation was shown to have a density of 1.195 g/cm3 in sucrose density gradients. Under the conditions used, CsCl centrifugation caused disruption of the virus and less than 5% of input infectivity could be recovered from the virus peak at 1.23 g/cm3. As in other fiaviviruses, three polypeptides (V1, V2, V3) were detected by polyacrylamide gel electrophoresis in radioactively labelled purified TBE virus. After disruption of TBE virus with Nonidet P-40, Tween-80/Tri-(n-butyl)-phosphate or sodium deoxycholate, a 120--130 S nucleoprotein could be separated by rate zonal centrifugation from more slowly sedimenting haemagglutinins. Immunization of mice with these haemagglutinins showed that they induced haemagglutination inhibiting, neutralizing and complement fixing antibodies. A pronounced increase in immunogenicity could be observed by the use of Al(OH3) as an adjuvant.", "contents": "Characterization of tick-borne encephalitis virus and immunogenicity of its surface components in mice. Tick-borne encephalitis (TBE) virus grown in chick embryo cells and purified by rate-zonal centrifugation was shown to have a density of 1.195 g/cm3 in sucrose density gradients. Under the conditions used, CsCl centrifugation caused disruption of the virus and less than 5% of input infectivity could be recovered from the virus peak at 1.23 g/cm3. As in other fiaviviruses, three polypeptides (V1, V2, V3) were detected by polyacrylamide gel electrophoresis in radioactively labelled purified TBE virus. After disruption of TBE virus with Nonidet P-40, Tween-80/Tri-(n-butyl)-phosphate or sodium deoxycholate, a 120--130 S nucleoprotein could be separated by rate zonal centrifugation from more slowly sedimenting haemagglutinins. Immunization of mice with these haemagglutinins showed that they induced haemagglutination inhibiting, neutralizing and complement fixing antibodies. A pronounced increase in immunogenicity could be observed by the use of Al(OH3) as an adjuvant."}
{"id": "PMID:20766", "title": "Potentiation of langat virus infection by lead intoxication--influence on host defenses.", "content": "Pathogenesis was studied in mice with moderate levels of lead intoxication after Langat virus infection. Both lead chloride and lead nitrate increased mortality by 40--50%. This increase was associated with decreased in vivo interferon and neutralizing antibody synthesis. The increased mortality was associated with enhancement of viral growth in peripheral tissues as evidenced by early appearing and long-lasting high titer viremia following lead intoxication. This resulted in early penetration of blood brain barrier and led to much higher virus titers in the brain. The data strongly suggest that lead increased mortality following infection by complex means, the most important being the enhacement of encephalitogenic potential of Langat virus.", "contents": "Potentiation of langat virus infection by lead intoxication--influence on host defenses. Pathogenesis was studied in mice with moderate levels of lead intoxication after Langat virus infection. Both lead chloride and lead nitrate increased mortality by 40--50%. This increase was associated with decreased in vivo interferon and neutralizing antibody synthesis. The increased mortality was associated with enhancement of viral growth in peripheral tissues as evidenced by early appearing and long-lasting high titer viremia following lead intoxication. This resulted in early penetration of blood brain barrier and led to much higher virus titers in the brain. The data strongly suggest that lead increased mortality following infection by complex means, the most important being the enhacement of encephalitogenic potential of Langat virus."}
{"id": "PMID:20767", "title": "Non-infectious antigen for laboratory diagnosis of Japanese encephalitis.", "content": "Sucrose-acetone suckling mouse brain antigens of Na-kayama NIH, JaGAr-01 and Peking-1 strains of Japanese encephalitis (JE) virus treated with beta-propiolactone (BPL) retained their ability to specifically react in haemagglutination inhibition (HI) tests with antibody to JE virus, as demonstrated with convalescent sera. BPL treatment abolished the infectivity but did not affect the haemagglutinating activity of the virus of the pH optimum of the haemagglutination (HA) test.", "contents": "Non-infectious antigen for laboratory diagnosis of Japanese encephalitis. Sucrose-acetone suckling mouse brain antigens of Na-kayama NIH, JaGAr-01 and Peking-1 strains of Japanese encephalitis (JE) virus treated with beta-propiolactone (BPL) retained their ability to specifically react in haemagglutination inhibition (HI) tests with antibody to JE virus, as demonstrated with convalescent sera. BPL treatment abolished the infectivity but did not affect the haemagglutinating activity of the virus of the pH optimum of the haemagglutination (HA) test."}
{"id": "PMID:20768", "title": "Measles antibodies in nasal secretions and sera of children with measles.", "content": "Measles antibodies were determined, in the course of measles, in sera and nasal secretions of 54 and 27 children, respectively. The examinations were performed on the 3rd or 4th day (1st period) and between the 10th and 14th day (2nd period) after onset of rash in both sera and nasal secretions and after 25 to 60 days (3rd period) in sera only. Geometric mean titres of antibodies in sera determined by haemmagglutination inhibition (HI) and neutralization tests in the 1st period were 126.3 and 115.3 respectively. For the 2nd period the respective figures were 318.4 and 396.1 and for the 3rd period--388.0 and 445.6. Fractionation on Sephadex G-200 of sera from the 1st period revealed HI and neutralizaing antibodies associated mainly with the IgM serum globulin class. Measles HI and neutralizing antibodies were also found in nasal secretions of all 27 children, but their titres were much lower than in serum. The antibodies determined by indirect immunofluorescence in nasal secretions were associated with IgA in 26 and with IgG immunoglobulin in 15 of the 27 subjects. No IgM antibodies were found.", "contents": "Measles antibodies in nasal secretions and sera of children with measles. Measles antibodies were determined, in the course of measles, in sera and nasal secretions of 54 and 27 children, respectively. The examinations were performed on the 3rd or 4th day (1st period) and between the 10th and 14th day (2nd period) after onset of rash in both sera and nasal secretions and after 25 to 60 days (3rd period) in sera only. Geometric mean titres of antibodies in sera determined by haemmagglutination inhibition (HI) and neutralization tests in the 1st period were 126.3 and 115.3 respectively. For the 2nd period the respective figures were 318.4 and 396.1 and for the 3rd period--388.0 and 445.6. Fractionation on Sephadex G-200 of sera from the 1st period revealed HI and neutralizaing antibodies associated mainly with the IgM serum globulin class. Measles HI and neutralizing antibodies were also found in nasal secretions of all 27 children, but their titres were much lower than in serum. The antibodies determined by indirect immunofluorescence in nasal secretions were associated with IgA in 26 and with IgG immunoglobulin in 15 of the 27 subjects. No IgM antibodies were found."}
{"id": "PMID:20769", "title": "Comparison of interferon-inducing activities and antiviral effects of tobacco mosaic virus, tilorone and sodium nucleinate.", "content": "Endogenous interferon was produced in animals in response to the administration of tobacco mosaic virus (TMV), tilorone and sodium nucleinate. The relationship between interferon production and the kind of inducer and the route of its administration was studied. TMV was completely innocuous for Macaca rhesus monkeys and mice and caused no untoward effects in humans upon peroral administration. TMV, tilorone and sodium nucleinate given per os exerted a marked protective effect in mice against tick-borne encephalitis, eastern and western equine encephalomyelitis and influenza virus infections.", "contents": "Comparison of interferon-inducing activities and antiviral effects of tobacco mosaic virus, tilorone and sodium nucleinate. Endogenous interferon was produced in animals in response to the administration of tobacco mosaic virus (TMV), tilorone and sodium nucleinate. The relationship between interferon production and the kind of inducer and the route of its administration was studied. TMV was completely innocuous for Macaca rhesus monkeys and mice and caused no untoward effects in humans upon peroral administration. TMV, tilorone and sodium nucleinate given per os exerted a marked protective effect in mice against tick-borne encephalitis, eastern and western equine encephalomyelitis and influenza virus infections."}
{"id": "PMID:20770", "title": "Transmission of alfalfa mosaic virus through Nicandra physaloides seeds and its localization in embryo cotyledons.", "content": "Alfalfa mosaic virus (AMV) was found to be transmitted through seeds of Nicandra physaloids L. The average seed transmission rate of the AMV isolates T6, LMBG-4 and ST amounted to 23, 4 and 0 per cent, repectively. In the cytoplasm of parenchyma cells of embryo cotyledons of seeds from plants infected with the T6 isolate, electron microscopy revealed AMV aggregates of type 2A and aggregations of irregularly viral particles with a tendency to subparallel alignment, representing early stages of type 2A aggregates.", "contents": "Transmission of alfalfa mosaic virus through Nicandra physaloides seeds and its localization in embryo cotyledons. Alfalfa mosaic virus (AMV) was found to be transmitted through seeds of Nicandra physaloids L. The average seed transmission rate of the AMV isolates T6, LMBG-4 and ST amounted to 23, 4 and 0 per cent, repectively. In the cytoplasm of parenchyma cells of embryo cotyledons of seeds from plants infected with the T6 isolate, electron microscopy revealed AMV aggregates of type 2A and aggregations of irregularly viral particles with a tendency to subparallel alignment, representing early stages of type 2A aggregates."}
{"id": "PMID:20771", "title": "Simple method for preparation of immune sera to envelope and nucleocapsid antigens of Semliki Forest virus.", "content": "Immune sera to the envelope and nucleocapsid components of Zaisan 260 and R 16225 strains of Semliki Forest virus (SFV) were prepared with the use of disrupted, partially purified virus.", "contents": "Simple method for preparation of immune sera to envelope and nucleocapsid antigens of Semliki Forest virus. Immune sera to the envelope and nucleocapsid components of Zaisan 260 and R 16225 strains of Semliki Forest virus (SFV) were prepared with the use of disrupted, partially purified virus."}
{"id": "PMID:20773", "title": "Chemical interactions between thiamin and tannic acid. II. Separation of products.", "content": "Bio Rex 70 column chromatography and high voltage paper electrophoresis were used to fractionate and define the reaction products of thiamin-tannic acid and thiamin-tea mixtures. Fractions separated indicated the presence of (a) thiamin-tannic acid adduct(s) and several modified forms of thiamin among the products. Using radioactive thiamin and determining the intact form by scintillation counting, the extent of thiamin modification under various conditions was compared with previous results as determined by the thiochrome method. The elution profile of the thiamin-tea mixture and the electrophoretogram showed features similar to those of the thiamin-tannic acid mixture. The effectiveness of the tea extract and tannic acid in modifying thiamin was compared. Ascorbic acid was found to protect the modification of thiamin by tannic acid, not only at acidic pH as previously found, but also at neutral pH, thus making vitamin C a strong candidate for the protection of thiamin in the alimentary system.", "contents": "Chemical interactions between thiamin and tannic acid. II. Separation of products. Bio Rex 70 column chromatography and high voltage paper electrophoresis were used to fractionate and define the reaction products of thiamin-tannic acid and thiamin-tea mixtures. Fractions separated indicated the presence of (a) thiamin-tannic acid adduct(s) and several modified forms of thiamin among the products. Using radioactive thiamin and determining the intact form by scintillation counting, the extent of thiamin modification under various conditions was compared with previous results as determined by the thiochrome method. The elution profile of the thiamin-tea mixture and the electrophoretogram showed features similar to those of the thiamin-tannic acid mixture. The effectiveness of the tea extract and tannic acid in modifying thiamin was compared. Ascorbic acid was found to protect the modification of thiamin by tannic acid, not only at acidic pH as previously found, but also at neutral pH, thus making vitamin C a strong candidate for the protection of thiamin in the alimentary system."}
{"id": "PMID:20774", "title": "Binding of zinc and iron to wheat bread, wheat bran, and their components.", "content": "Wholemeal wheat bread decreases the availability and intestinal absorption of divalent metals. To define this action further, binding of zinc in vitro to a wheat wholemeal bread (Tanok), dephytinized Tanok, and cellulose was determined at pH 5.0 to 7.5. Zinc binding by each was highly pH-dependent and reached a maximum at pH 6.5 to 7.5. Removal of phytate from Tanok did not reduce its binding capability. Wheat bran at pH 6.5 and 6.8 bound 72% of iron (0.5 microgram/ml of solution) and 82.5% of zinc (1.43 microgram/ml solution), respectively. Lignin and two of the hemicellulose fractions of wheat bran and high binding capabilities for zinc (85.6, 87.1, and 82.1%, respectively) whereas a third had a lower zinc-binding capability (38.7%). Binding of zinc to various celluloses and dextrans is also demonstrated. Formation of complexes of these metals with wheat fiber can explain, at least in part, the decreased availability of dietary iron and zinc in wholemeal wheat bread.", "contents": "Binding of zinc and iron to wheat bread, wheat bran, and their components. Wholemeal wheat bread decreases the availability and intestinal absorption of divalent metals. To define this action further, binding of zinc in vitro to a wheat wholemeal bread (Tanok), dephytinized Tanok, and cellulose was determined at pH 5.0 to 7.5. Zinc binding by each was highly pH-dependent and reached a maximum at pH 6.5 to 7.5. Removal of phytate from Tanok did not reduce its binding capability. Wheat bran at pH 6.5 and 6.8 bound 72% of iron (0.5 microgram/ml of solution) and 82.5% of zinc (1.43 microgram/ml solution), respectively. Lignin and two of the hemicellulose fractions of wheat bran and high binding capabilities for zinc (85.6, 87.1, and 82.1%, respectively) whereas a third had a lower zinc-binding capability (38.7%). Binding of zinc to various celluloses and dextrans is also demonstrated. Formation of complexes of these metals with wheat fiber can explain, at least in part, the decreased availability of dietary iron and zinc in wholemeal wheat bread."}
{"id": "PMID:20776", "title": "Ionic flux across canine duodenum. Movement of bicarbonate.", "content": "Effect of isosmotic biocarbonate-rich solutions on the Brunner's gland area were studied by means of proximal duodenal explants in eight anesthetized dogs. Volume gain occurred with all instillates and varied indirectly with the concentration of the bicarbonate in the instilled solutions. Net bicarbonate gain occurred with instillate of 40 mEq./1.; net insorption occurred with instillates of higher bicarbonate concentration, the rate of which was dependent on the instillate concentration. Insorption of chloride occurred with the lower bicarbonate solutions and enterosorption occurred at higher concentrations. The modification of intraluminal bicarbonate by the proximal duodenal mucosa is important in the regulation of intraduodenal pH and abnormal function of this mechanism may play a role in the pathogenesis of duodenal ulceration because of incomplete hydrochloric acid neutralization.", "contents": "Ionic flux across canine duodenum. Movement of bicarbonate. Effect of isosmotic biocarbonate-rich solutions on the Brunner's gland area were studied by means of proximal duodenal explants in eight anesthetized dogs. Volume gain occurred with all instillates and varied indirectly with the concentration of the bicarbonate in the instilled solutions. Net bicarbonate gain occurred with instillate of 40 mEq./1.; net insorption occurred with instillates of higher bicarbonate concentration, the rate of which was dependent on the instillate concentration. Insorption of chloride occurred with the lower bicarbonate solutions and enterosorption occurred at higher concentrations. The modification of intraluminal bicarbonate by the proximal duodenal mucosa is important in the regulation of intraduodenal pH and abnormal function of this mechanism may play a role in the pathogenesis of duodenal ulceration because of incomplete hydrochloric acid neutralization."}
{"id": "PMID:20777", "title": "Necrotizing vasculitis of the gallbladder and the appendix. Similarity in the morphology of rheumatoid arteritis and Polyarteritis nodosa.", "content": "Two patients with rheumatoid arthritis (RA) and polyarteritis nodosa (PN) presented with abdominal pain. Both revealed necrotizing vasculitis of the gallbladder and the appendix respectively. The controversial role of corticosteroids in the pathogenesis of rheumatoid arteritis, the rarity of rheumatoid arteritis of the gallbladder and the morphologic similarity of the vascular lesion in the gallbladder and appendix are discussed.", "contents": "Necrotizing vasculitis of the gallbladder and the appendix. Similarity in the morphology of rheumatoid arteritis and Polyarteritis nodosa. Two patients with rheumatoid arthritis (RA) and polyarteritis nodosa (PN) presented with abdominal pain. Both revealed necrotizing vasculitis of the gallbladder and the appendix respectively. The controversial role of corticosteroids in the pathogenesis of rheumatoid arteritis, the rarity of rheumatoid arteritis of the gallbladder and the morphologic similarity of the vascular lesion in the gallbladder and appendix are discussed."}
{"id": "PMID:20778", "title": "The effect of ethanol and bile on electrolyte movement across canine proximal duodenal mucosa.", "content": "The existence of a gastric mucosal barrier, controlling H+ N+ flux has been well established. The disruption of this barrier by ethanol and bile has also been confirmed. This study was designed to investigate the effect of ethanol and bile on the duodenal mucosa, which, as we have shown, is similar to gastric mucosa in that there is H+, Na+ flux. In 10 dogs, duodenal explants with an intact blood supply were placed within lucite chambers. Under basal conditions there was H+ insorption and Na+ exsorption. Neither bile nor ethanol caused increased H+ Na+ flux. Acute erosions did not develop in the proximal duodenum, as has been shown to occur when bile or ethanol is instilled into the stomach. These studies, therefore, demonstrate that although H+ Na+ occurs across the duodenal mucosa, bile or ethanol do not cause changes in ionic flux and acute erosions do not develop.", "contents": "The effect of ethanol and bile on electrolyte movement across canine proximal duodenal mucosa. The existence of a gastric mucosal barrier, controlling H+ N+ flux has been well established. The disruption of this barrier by ethanol and bile has also been confirmed. This study was designed to investigate the effect of ethanol and bile on the duodenal mucosa, which, as we have shown, is similar to gastric mucosa in that there is H+, Na+ flux. In 10 dogs, duodenal explants with an intact blood supply were placed within lucite chambers. Under basal conditions there was H+ insorption and Na+ exsorption. Neither bile nor ethanol caused increased H+ Na+ flux. Acute erosions did not develop in the proximal duodenum, as has been shown to occur when bile or ethanol is instilled into the stomach. These studies, therefore, demonstrate that although H+ Na+ occurs across the duodenal mucosa, bile or ethanol do not cause changes in ionic flux and acute erosions do not develop."}
{"id": "PMID:20781", "title": "Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis.", "content": "N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.", "contents": "Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis. N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines."}
{"id": "PMID:20783", "title": "Blockade of myocardial slow inward current at low pH.", "content": "The effect of low pH on the slow cationic inward current was studied in isolated perfused embryonic chick ventricles (16-21 days old). In order to study the slow current, the fast Na+ current was inactivated by partial depolarization to about -40 mV by elevation of K+ (25 mM). Subsequent exposure of the tissue to catecholamines or methylxanthines allowed slowly rising overshooting electrical responses (the \"slow response\") with with accompanying contractions to be elicited by electrical stimulation. These slow responses are insensitive to tetrodotoxin and are Na+- and Ca2+-dependent. It was found that the isoproterenol- and caffeine-induced slow responses were abolished at about pH 6.1; 50% inhibition occurred at about pH 6.5. The rate of rise of the normal action potential, which is dependent on a fast Na+ current, was only slightly affected at these same pH levels; however, electromechanical uncoupling occurred, as expected from inhibition of the slow current. Therefore, the slow current was blocked at an acid pH that did not block the fast Na+ current.", "contents": "Blockade of myocardial slow inward current at low pH. The effect of low pH on the slow cationic inward current was studied in isolated perfused embryonic chick ventricles (16-21 days old). In order to study the slow current, the fast Na+ current was inactivated by partial depolarization to about -40 mV by elevation of K+ (25 mM). Subsequent exposure of the tissue to catecholamines or methylxanthines allowed slowly rising overshooting electrical responses (the \"slow response\") with with accompanying contractions to be elicited by electrical stimulation. These slow responses are insensitive to tetrodotoxin and are Na+- and Ca2+-dependent. It was found that the isoproterenol- and caffeine-induced slow responses were abolished at about pH 6.1; 50% inhibition occurred at about pH 6.5. The rate of rise of the normal action potential, which is dependent on a fast Na+ current, was only slightly affected at these same pH levels; however, electromechanical uncoupling occurred, as expected from inhibition of the slow current. Therefore, the slow current was blocked at an acid pH that did not block the fast Na+ current."}
{"id": "PMID:20785", "title": "Rio Grande--a new phlebotomus fever group virus from south Texas.", "content": "Three strains of a new Phlebotomus fever group virus were isolated from pack rats (Neotoma micropus) collected in south Texas during 1973--1974; the name Rio Grande was proposed for this virus. The virus is pH 3.0 labile, sensitive to the action of sodium deoxycholate and heat (56 degrees C) labile. The results of a serosurvey indicated that pack rats are probably the principal vertebrate host for Rio Grande virus and that year-round transmission of the virus may occur. Because no isolations of this virus were made from hematophagous insects, the vector, if any, remains undetermined.", "contents": "Rio Grande--a new phlebotomus fever group virus from south Texas. Three strains of a new Phlebotomus fever group virus were isolated from pack rats (Neotoma micropus) collected in south Texas during 1973--1974; the name Rio Grande was proposed for this virus. The virus is pH 3.0 labile, sensitive to the action of sodium deoxycholate and heat (56 degrees C) labile. The results of a serosurvey indicated that pack rats are probably the principal vertebrate host for Rio Grande virus and that year-round transmission of the virus may occur. Because no isolations of this virus were made from hematophagous insects, the vector, if any, remains undetermined."}
{"id": "PMID:20788", "title": "Multiple endocrine adenomatosis type IIB. Report of two cases and review of the literature.", "content": "The combination of bilateral medullary thyroid cancer, bilateral pheochromocytoma, Marfanoid body habitus with arachnodactyly, pectus excavatum, mucosal neuromas, and hyperplastic corneal nerves has become recognized as a definite entity, multiple endocrine adenomatosis (MEA) Type IIB. Two cases of MEA Type IIB are described, along with diagnosis, treatment, pitfalls in management, and related syndromes. When this syndrome is suspected, a careful search for other hyperfunctioning endocrine glands, particularly pheochromocytoma, must be made. Failure to recognize pheochromocytoma may prove a serious hazard if thyroidectomy is the initial procedure. The value of thyrocalcitonin as an indicator of the presence of medullary thyroid cancer and its value as a familial screening test are discussed.", "contents": "Multiple endocrine adenomatosis type IIB. Report of two cases and review of the literature. The combination of bilateral medullary thyroid cancer, bilateral pheochromocytoma, Marfanoid body habitus with arachnodactyly, pectus excavatum, mucosal neuromas, and hyperplastic corneal nerves has become recognized as a definite entity, multiple endocrine adenomatosis (MEA) Type IIB. Two cases of MEA Type IIB are described, along with diagnosis, treatment, pitfalls in management, and related syndromes. When this syndrome is suspected, a careful search for other hyperfunctioning endocrine glands, particularly pheochromocytoma, must be made. Failure to recognize pheochromocytoma may prove a serious hazard if thyroidectomy is the initial procedure. The value of thyrocalcitonin as an indicator of the presence of medullary thyroid cancer and its value as a familial screening test are discussed."}
{"id": "PMID:20790", "title": "[Continuity of life situation and \"successful\" aging (author's transl)].", "content": "The determinants of \"successful\" aging have been a main concern in social gerontological research. The Continuity Hypothesis suggests that there is a relationship between an older person's life satisfaction and the similarity of his social life situation in middle adulthood and in old age. The old person is the more likely to score low in life satisfaction the less similar his old age situation to his life situation in middle adulthood. This hypothesis has been tested in summer 1973 in Cologne with a sample of 406 people aged 65 and over. Findings indicate that continuity of life situation may be an important variable accounting for life satisfaction in old age. Moreover, it could be shown that the various negatively experienced life changes since adulthoood formed a complex of interacting variables, thereby increasing the negative effect on the old person's life satisfaction. Health proved to be one of the most important variables. The continuity hypothesis as stated here represents a modified version of activity theory.", "contents": "[Continuity of life situation and \"successful\" aging (author's transl)]. The determinants of \"successful\" aging have been a main concern in social gerontological research. The Continuity Hypothesis suggests that there is a relationship between an older person's life satisfaction and the similarity of his social life situation in middle adulthood and in old age. The old person is the more likely to score low in life satisfaction the less similar his old age situation to his life situation in middle adulthood. This hypothesis has been tested in summer 1973 in Cologne with a sample of 406 people aged 65 and over. Findings indicate that continuity of life situation may be an important variable accounting for life satisfaction in old age. Moreover, it could be shown that the various negatively experienced life changes since adulthoood formed a complex of interacting variables, thereby increasing the negative effect on the old person's life satisfaction. Health proved to be one of the most important variables. The continuity hypothesis as stated here represents a modified version of activity theory."}
{"id": "PMID:20791", "title": "[Psychic help for aged people of day-care-centers by attending person-centered encounter groups (author's transl)].", "content": "45 old people (Average age 72 years) took part in 9 person-centered encounter groups together with younger people (Average age 32 years). Psychological changes of the old people were collected by questionaires and compared to a control group of 38 old people who subsequently took part in 4 encounter groups without younger people. Excerpts from the encounter talks were rated in certain variables. delta The old people of the mixed aged encounter groups showed constructive psychological changes after participation, for example reduced feelings of loneliness, reduced stress with emotional problems, and they see ageing less resignative. The mixed aged encounter groups were more helpful for the old people than the groups without younger people. The old people of the mixed group were more emotionally occupied by their own person, they showed more self-exploration and self-acceptance, they talked with more emotional engagement about their experiences and were more genuine; 3 months later their self-disclosure in an interview with a stranger was higher.", "contents": "[Psychic help for aged people of day-care-centers by attending person-centered encounter groups (author's transl)]. 45 old people (Average age 72 years) took part in 9 person-centered encounter groups together with younger people (Average age 32 years). Psychological changes of the old people were collected by questionaires and compared to a control group of 38 old people who subsequently took part in 4 encounter groups without younger people. Excerpts from the encounter talks were rated in certain variables. delta The old people of the mixed aged encounter groups showed constructive psychological changes after participation, for example reduced feelings of loneliness, reduced stress with emotional problems, and they see ageing less resignative. The mixed aged encounter groups were more helpful for the old people than the groups without younger people. The old people of the mixed group were more emotionally occupied by their own person, they showed more self-exploration and self-acceptance, they talked with more emotional engagement about their experiences and were more genuine; 3 months later their self-disclosure in an interview with a stranger was higher."}
{"id": "PMID:20792", "title": "[Poverty in old age (author's transl)].", "content": "The legitimate claim on social assistance riveted in the Federal Legislation on Social Welfare and deduced from the welfare-state-postulate of the Constitution is only partially valid (obligatory assistance only). Applying this claim substantially is legally tied to discretionary decisions of the administration. Handling such estimates in a restrictive way makes the legitimate claim invalide. Social values are significantly determined by equivalent-maxims. Claims on social assistance, however, are not being deduced from preperformances (in a judical sense in regard of pensions) but are being derived from a diffuse claim on a social state incured with the odium of statutory relief for the necessitous. It is empirically provable that the causes for need of social assistance are of a social kind. Therefore, the claim on social assistance can only be a claim to \"reparation\". This understanding could be seen as an adequate basis for a progressive administration of social welfare.", "contents": "[Poverty in old age (author's transl)]. The legitimate claim on social assistance riveted in the Federal Legislation on Social Welfare and deduced from the welfare-state-postulate of the Constitution is only partially valid (obligatory assistance only). Applying this claim substantially is legally tied to discretionary decisions of the administration. Handling such estimates in a restrictive way makes the legitimate claim invalide. Social values are significantly determined by equivalent-maxims. Claims on social assistance, however, are not being deduced from preperformances (in a judical sense in regard of pensions) but are being derived from a diffuse claim on a social state incured with the odium of statutory relief for the necessitous. It is empirically provable that the causes for need of social assistance are of a social kind. Therefore, the claim on social assistance can only be a claim to \"reparation\". This understanding could be seen as an adequate basis for a progressive administration of social welfare."}
{"id": "PMID:20793", "title": "[Causes and outward forms of poverty in old age (author's transl)].", "content": "In the Federal Rupublic nearly 20% of the elderly people live on the edge of below the property-line, which is well-marked by public assistance. In spite of legal claims 75% of the needy elderly do not explore all possible avenues. The ascertainment of this high percentage which had been never estimated exactly-about which, hitherto, impressionistic or opportunistic declarations have been made rather than reliable assertions-is a result of a representative empirical research. The authors have conducted structured interviews, analysis of official files and explorative interviews with old people and with those who are, in a broad sense, competent regarding their need. The analysis of the old peoples' social biographies significantly showed the invariance regarding the class the necessitous belong to; generally workers or people of the farming section either become or remain poor. Deficient vocational education is the beginning of a lifelong outstanding external determination. Their non-problematical replaceability at work surrenders them to the enterpreneur's calculation. When growing older they often endure professional depreciation and financial reduction. After they have retired, need encreases. Individual failure is not the cause for poverty, however the belonging to the working-classes; all those belonging to these classes are potentially poor, due to their replaceability and exchangeability at work. At the lower end of the class-hierarchy potential poverty changes into actual poverty. Causative regarding formation of these classes is the fact, that the material possibilities of the social production cannot be used by the actual producers. The causes for poverty which reproduces itself always within the same classes can't be removed by legal means which can only relief poverty.", "contents": "[Causes and outward forms of poverty in old age (author's transl)]. In the Federal Rupublic nearly 20% of the elderly people live on the edge of below the property-line, which is well-marked by public assistance. In spite of legal claims 75% of the needy elderly do not explore all possible avenues. The ascertainment of this high percentage which had been never estimated exactly-about which, hitherto, impressionistic or opportunistic declarations have been made rather than reliable assertions-is a result of a representative empirical research. The authors have conducted structured interviews, analysis of official files and explorative interviews with old people and with those who are, in a broad sense, competent regarding their need. The analysis of the old peoples' social biographies significantly showed the invariance regarding the class the necessitous belong to; generally workers or people of the farming section either become or remain poor. Deficient vocational education is the beginning of a lifelong outstanding external determination. Their non-problematical replaceability at work surrenders them to the enterpreneur's calculation. When growing older they often endure professional depreciation and financial reduction. After they have retired, need encreases. Individual failure is not the cause for poverty, however the belonging to the working-classes; all those belonging to these classes are potentially poor, due to their replaceability and exchangeability at work. At the lower end of the class-hierarchy potential poverty changes into actual poverty. Causative regarding formation of these classes is the fact, that the material possibilities of the social production cannot be used by the actual producers. The causes for poverty which reproduces itself always within the same classes can't be removed by legal means which can only relief poverty."}
{"id": "PMID:20794", "title": "[Significance of environmental hygiene for aging individuals (author's transl)].", "content": "Problems in the field of modern hygiene have changed in parallel with the current shift of morbidity and mortality in the direction of non-infections diseases such as vascular and circulatory disturbances and malignant tumors. As a consequence, hygienic care for the aged is becoming increasingly more important, and with it the close association between Hygiene and the sciences of Gerontology and Geriatrics. Because of long-term, chronic exposure via air, food, and drinking-water, environmental carcinogens such as the P.A.H. and nitrosamines constitute serious health hazards especially in advanced old age. Also, the accumulation in human body fat of biocides of the class of chlorinated hydrocarbons (e.G. DDT) must be considered an alarming finding, since toxic effects may be expected as a result of fat resorption in elderly subjects. Thus, there is a need for the further development and broadening of the field of Gerohygiene as an essential part of General Gerontology.", "contents": "[Significance of environmental hygiene for aging individuals (author's transl)]. Problems in the field of modern hygiene have changed in parallel with the current shift of morbidity and mortality in the direction of non-infections diseases such as vascular and circulatory disturbances and malignant tumors. As a consequence, hygienic care for the aged is becoming increasingly more important, and with it the close association between Hygiene and the sciences of Gerontology and Geriatrics. Because of long-term, chronic exposure via air, food, and drinking-water, environmental carcinogens such as the P.A.H. and nitrosamines constitute serious health hazards especially in advanced old age. Also, the accumulation in human body fat of biocides of the class of chlorinated hydrocarbons (e.G. DDT) must be considered an alarming finding, since toxic effects may be expected as a result of fat resorption in elderly subjects. Thus, there is a need for the further development and broadening of the field of Gerohygiene as an essential part of General Gerontology."}
{"id": "PMID:20795", "title": "[Education: a theme in gerontology (author's transl)].", "content": "The paper presents a review of the history of educational gerontology (\"andragogy\" or \"gerontagogy\") which has a special role within the field of gerontology. Whereas gerontological sciences such as biology, medicine, psychology, and sociology in (frequently interdisciplinary) approaches study the process of aging, educational gerontology makes use of the findings of these research areas, intending to influence the process of aging. There is a need for education in old age - provided this is not restricted to the acquisition of knowledge and skills or the extension of academic training into old age. It is stressed that an offer of \"education for the aged\" or even of \"help for the life in age\" very ofter is rejected by old people as they are induced to feel incompetent when invited to school and training courses of that kind. Future \"gerontagogy\" will have to notice and to respect resistance of that kind and will have to endeavour to increase the motivation to learn in old age in adequate ways. A first goal of educational gerontology should be to develop programs going beyond those developed for children and realized in traditional institutions of pedagogy. Referring to results of differential gerontology programs for \"educating\" and \"stimulating\" aged persons will have to be rather variable to fit individual goals and motivations of the old. The differential approach necessary to meet individual and rather specific demands will require a more thorough \"training of trainers\" than is realized today in the Federal Republic of Germany.", "contents": "[Education: a theme in gerontology (author's transl)]. The paper presents a review of the history of educational gerontology (\"andragogy\" or \"gerontagogy\") which has a special role within the field of gerontology. Whereas gerontological sciences such as biology, medicine, psychology, and sociology in (frequently interdisciplinary) approaches study the process of aging, educational gerontology makes use of the findings of these research areas, intending to influence the process of aging. There is a need for education in old age - provided this is not restricted to the acquisition of knowledge and skills or the extension of academic training into old age. It is stressed that an offer of \"education for the aged\" or even of \"help for the life in age\" very ofter is rejected by old people as they are induced to feel incompetent when invited to school and training courses of that kind. Future \"gerontagogy\" will have to notice and to respect resistance of that kind and will have to endeavour to increase the motivation to learn in old age in adequate ways. A first goal of educational gerontology should be to develop programs going beyond those developed for children and realized in traditional institutions of pedagogy. Referring to results of differential gerontology programs for \"educating\" and \"stimulating\" aged persons will have to be rather variable to fit individual goals and motivations of the old. The differential approach necessary to meet individual and rather specific demands will require a more thorough \"training of trainers\" than is realized today in the Federal Republic of Germany."}
{"id": "PMID:20796", "title": "[Interrelationship of motivation and barriers in the learning process in old age (author's transl)].", "content": "Started from the concept of lifelong learning it is discussed that the relation between motivation and barriers or obstructions has important influence on learning in old age. Even if differential view has been regarded, in general we may suppose that motivation will have a decreasing tendency and barriers an increasing tendency in old age. This concept is seen together with Welford's Cost- and Benefit-Theory (1976), discussed for Motivation, Capacity, Learning and Age. Consequences would be to look for measures to increase the motivation and decrease the barriers as far as possible.", "contents": "[Interrelationship of motivation and barriers in the learning process in old age (author's transl)]. Started from the concept of lifelong learning it is discussed that the relation between motivation and barriers or obstructions has important influence on learning in old age. Even if differential view has been regarded, in general we may suppose that motivation will have a decreasing tendency and barriers an increasing tendency in old age. This concept is seen together with Welford's Cost- and Benefit-Theory (1976), discussed for Motivation, Capacity, Learning and Age. Consequences would be to look for measures to increase the motivation and decrease the barriers as far as possible."}
{"id": "PMID:20797", "title": "[Consistency and variability of intellectual and psychomotor abilities in aged people (author's transl)].", "content": "Several methods of statistical analyses, featuring as well group specific changes and intra-individual changes, in an investigation of intelligence, psychomotor abilities of 121 aged men and women over a period of 7 years, lead to results that there are many different aspects of consistancy and change. An attempt is made to discuss these results in the framework of differential and developmental psychological aspects.", "contents": "[Consistency and variability of intellectual and psychomotor abilities in aged people (author's transl)]. Several methods of statistical analyses, featuring as well group specific changes and intra-individual changes, in an investigation of intelligence, psychomotor abilities of 121 aged men and women over a period of 7 years, lead to results that there are many different aspects of consistancy and change. An attempt is made to discuss these results in the framework of differential and developmental psychological aspects."}
{"id": "PMID:20798", "title": "[Evaluating programs for preparation to old age: some theoretical thoughts and a practical example (author's transl)].", "content": "In the first part methodically satisfactory experimental designs for evaluating programs for preparation to old age on the basis of Cambell & Stanely (1963) are sketched including conditions which hinder the realization of the ideal notions. In the second part an experiment for comparing two preparatory courses to old age using different methods of instruction is described. It was observed that the more demanding teaching method resulted in more anxiety for old age. This led to the conclusion, that programs for preparation to old age should be planned as a sequence of several units in which the mastering of the new ideas may be learned and in which this learning process may be supervised.", "contents": "[Evaluating programs for preparation to old age: some theoretical thoughts and a practical example (author's transl)]. In the first part methodically satisfactory experimental designs for evaluating programs for preparation to old age on the basis of Cambell & Stanely (1963) are sketched including conditions which hinder the realization of the ideal notions. In the second part an experiment for comparing two preparatory courses to old age using different methods of instruction is described. It was observed that the more demanding teaching method resulted in more anxiety for old age. This led to the conclusion, that programs for preparation to old age should be planned as a sequence of several units in which the mastering of the new ideas may be learned and in which this learning process may be supervised."}
{"id": "PMID:20799", "title": "[Academic learn in old age (author's transl)].", "content": "To test the capacity of the elderly to sustain prolonged intellectual activity, 80 volunteers from 60 to 90 years of age received instruction in reading German, previously not studied by them. Special methods of instruction were employed to stimulate interest and self confidence. Independent tests after three and six months showed that average progress was several times more rapid than that observed in high school children under normal conditions. Extremely beneficial effects on the personal attitudes of the participants resulted from the social contact involved. A later experiment involving learning to play the recorder produced similar results.", "contents": "[Academic learn in old age (author's transl)]. To test the capacity of the elderly to sustain prolonged intellectual activity, 80 volunteers from 60 to 90 years of age received instruction in reading German, previously not studied by them. Special methods of instruction were employed to stimulate interest and self confidence. Independent tests after three and six months showed that average progress was several times more rapid than that observed in high school children under normal conditions. Extremely beneficial effects on the personal attitudes of the participants resulted from the social contact involved. A later experiment involving learning to play the recorder produced similar results."}
{"id": "PMID:20800", "title": "[Age dependence of carbohydrate tolerance and insulin secretion (author's transl)].", "content": "In 81 healthy male volunteers with normal blood pressure, normal body weight of different age (18-58 years) an intravenous glucose tolerance test with determination of blood sugar and serum insulin levels was done. Furthermore triglycerids and total cholesterol serum levels were measured. The investigations have shown: 1. With increasing age - independent from relative body weight - a highly significant decrease of glucose tolerance controlled by means of k-value according to Conard is to be measured. 2. With increasing age significant decrease of insulinsecretion after intravenous application of glucose is to be measured. Basal serum insulin levels do not significant change with increasing age. 3. With increasing age significant increase of total cholesterol serum level is to be measured, whereas triglycerid serum levels do not change. 4. Because of the significant negative correlation between k-value and total cholesterol discussion is done, that disturbances in fat metabolism are able to lead to a further deteriosation of glucoseutilisation. The investigations have shown, that the diminished glucose tolerance with increasing age is mainly related to an insufficient function of the beta-cell with increasing age.", "contents": "[Age dependence of carbohydrate tolerance and insulin secretion (author's transl)]. In 81 healthy male volunteers with normal blood pressure, normal body weight of different age (18-58 years) an intravenous glucose tolerance test with determination of blood sugar and serum insulin levels was done. Furthermore triglycerids and total cholesterol serum levels were measured. The investigations have shown: 1. With increasing age - independent from relative body weight - a highly significant decrease of glucose tolerance controlled by means of k-value according to Conard is to be measured. 2. With increasing age significant decrease of insulinsecretion after intravenous application of glucose is to be measured. Basal serum insulin levels do not significant change with increasing age. 3. With increasing age significant increase of total cholesterol serum level is to be measured, whereas triglycerid serum levels do not change. 4. Because of the significant negative correlation between k-value and total cholesterol discussion is done, that disturbances in fat metabolism are able to lead to a further deteriosation of glucoseutilisation. The investigations have shown, that the diminished glucose tolerance with increasing age is mainly related to an insufficient function of the beta-cell with increasing age."}
{"id": "PMID:20801", "title": "[Manifest and latent folic acid deficiency in the aged (author's transl)].", "content": "The serum folate level of 100 aged persons (after 70) was decreased (less than 4 ng/ml) in 41% of the cases (manifest deficiency of folic acid). In the group of aged persons having normal folate values, in 41% of the cases the clearance method proved a latent folic acid deficiency, being the 15 minute value after 15 gamma/kg folic acid i.v., less than 25 ng/ml.", "contents": "[Manifest and latent folic acid deficiency in the aged (author's transl)]. The serum folate level of 100 aged persons (after 70) was decreased (less than 4 ng/ml) in 41% of the cases (manifest deficiency of folic acid). In the group of aged persons having normal folate values, in 41% of the cases the clearance method proved a latent folic acid deficiency, being the 15 minute value after 15 gamma/kg folic acid i.v., less than 25 ng/ml."}
{"id": "PMID:20802", "title": "[Importance of space analysis of U-moment-vectors concerning ageing people and chronical heart and blood circulation diseases (author's transl)].", "content": "U-vectors are a stabil component of electric activity of the heart repolarisation. The examinations of the space sizes and direction of the U-moment-vectors give an idea about the character of repolarisation of Purkinje's fibres and papillar muscles in old age and in chronical heart and blood circulation diseases. Pathological alteration of the U-vectors appear sooner and are more explicit than the T-vectors.", "contents": "[Importance of space analysis of U-moment-vectors concerning ageing people and chronical heart and blood circulation diseases (author's transl)]. U-vectors are a stabil component of electric activity of the heart repolarisation. The examinations of the space sizes and direction of the U-moment-vectors give an idea about the character of repolarisation of Purkinje's fibres and papillar muscles in old age and in chronical heart and blood circulation diseases. Pathological alteration of the U-vectors appear sooner and are more explicit than the T-vectors."}
{"id": "PMID:20803", "title": "[Analysis of gait in hemiplegics (author's transl)].", "content": "The gait of 31 hemiplegics is analyzed with a multiplecomponents force-plate. The healthy and paretic side differ in 5 of 7 parameters. The difference betwen the left and right side is bigger in the right hemiplegic, because in the left hemiplegic, the healthy side is more disturbed as in the right hemiplegic. That makes less differences between healthy and paretic side. The variability of the single steps is bigger in subjects with a bad gait. The method is suitable to screen the change of the gait and its progress.", "contents": "[Analysis of gait in hemiplegics (author's transl)]. The gait of 31 hemiplegics is analyzed with a multiplecomponents force-plate. The healthy and paretic side differ in 5 of 7 parameters. The difference betwen the left and right side is bigger in the right hemiplegic, because in the left hemiplegic, the healthy side is more disturbed as in the right hemiplegic. That makes less differences between healthy and paretic side. The variability of the single steps is bigger in subjects with a bad gait. The method is suitable to screen the change of the gait and its progress."}
{"id": "PMID:20804", "title": "[Geriatric aspects in operative treatment of intertrochanteric fractures (author's transl)].", "content": "On the basis of published data and of 702 osteosyntheses carried out using the Pohl sliding hip screw, the authors come to the conclusion that the mortality rate in geriatric patients is not correlated to the method of osteosynthesis used. Of utmost importance are immediate operation and early mobilisation. The osteosynthesis of intertrochanteric fractures in geriatric patients must facilitate early loading of the fracture site. This paper compares intramedullary nails, pertrochanteric blade plates, Y-nails and sliding hip screws, and contrasts these with the authors' own experience with the Pohl sliding hip screw.", "contents": "[Geriatric aspects in operative treatment of intertrochanteric fractures (author's transl)]. On the basis of published data and of 702 osteosyntheses carried out using the Pohl sliding hip screw, the authors come to the conclusion that the mortality rate in geriatric patients is not correlated to the method of osteosynthesis used. Of utmost importance are immediate operation and early mobilisation. The osteosynthesis of intertrochanteric fractures in geriatric patients must facilitate early loading of the fracture site. This paper compares intramedullary nails, pertrochanteric blade plates, Y-nails and sliding hip screws, and contrasts these with the authors' own experience with the Pohl sliding hip screw."}
{"id": "PMID:20805", "title": "[Morphological changes of the female urinary bladder in the elderly. Chronic infections of the urinary tract; the importance of their intensive treatment as preparatory measure for rehabilitation (author's transl)].", "content": "The urinary bladder of the elderly is showing a reduced adaptability on account of morphological changes; it is therefore more prone to infections. The morphological changes consist in a reduction of muscle fibres and in an increase of collagen fibres and in elastosis, furthermore in a sklerosis of the intramural arteries. 58% of our chronically - ill patients prove to have a chronic infection of the urinary tract.", "contents": "[Morphological changes of the female urinary bladder in the elderly. Chronic infections of the urinary tract; the importance of their intensive treatment as preparatory measure for rehabilitation (author's transl)]. The urinary bladder of the elderly is showing a reduced adaptability on account of morphological changes; it is therefore more prone to infections. The morphological changes consist in a reduction of muscle fibres and in an increase of collagen fibres and in elastosis, furthermore in a sklerosis of the intramural arteries. 58% of our chronically - ill patients prove to have a chronic infection of the urinary tract."}
{"id": "PMID:20808", "title": "[The pH-changes of the spinal fluid following bupivacaine (author's transl)].", "content": "The ph-changes of cerebral spinal fluid were measured following subarachnoid injection of bupivacaine 0.5% with and without adrenaline (1:200,000) during the three hours after the start of anaesthesia. At the same time drug precipitation was not detected. The ph-changes however, were pronounced but not enough to cause disturbances of the homoeostatic milieu. Especially no significant differences related to adrenaline were be found. The authors recommend bupivacaine 0.5% with and without adrenaline for spinal anaesthesia.", "contents": "[The pH-changes of the spinal fluid following bupivacaine (author's transl)]. The ph-changes of cerebral spinal fluid were measured following subarachnoid injection of bupivacaine 0.5% with and without adrenaline (1:200,000) during the three hours after the start of anaesthesia. At the same time drug precipitation was not detected. The ph-changes however, were pronounced but not enough to cause disturbances of the homoeostatic milieu. Especially no significant differences related to adrenaline were be found. The authors recommend bupivacaine 0.5% with and without adrenaline for spinal anaesthesia."}
{"id": "PMID:20820", "title": "Experimental cryptorchidism in adult male rats: histological and hormonal sequelae.", "content": "Mature male rats were rendered cryptorchid and followed for up to nine weeks during which serial blood specimens were obtained for multiple hormonal analyses; serial testicular samples were obtained as well. In contrast with control animals, cryptorchid rats showed transient rises in FSH which returned to normal at the end of the study; estrogen levels were high in the final weeks. Plasma testosterone levels were unchanged and LH levels changed little. Light and electron microscopic studies of testicular biopsy specimens showed prompt disruption of spermatogenesis which became more extensive with time. Sertoli cells underwent multiple changes including increased lipid storage and phagocytosis of spermatozoa. Comparisons are made between the sequence of hormonal changes and that of histological changes. In addition, questions are raised concerning the ways in which Sertoli cells are affected by experimental cryptorchidism.", "contents": "Experimental cryptorchidism in adult male rats: histological and hormonal sequelae. Mature male rats were rendered cryptorchid and followed for up to nine weeks during which serial blood specimens were obtained for multiple hormonal analyses; serial testicular samples were obtained as well. In contrast with control animals, cryptorchid rats showed transient rises in FSH which returned to normal at the end of the study; estrogen levels were high in the final weeks. Plasma testosterone levels were unchanged and LH levels changed little. Light and electron microscopic studies of testicular biopsy specimens showed prompt disruption of spermatogenesis which became more extensive with time. Sertoli cells underwent multiple changes including increased lipid storage and phagocytosis of spermatozoa. Comparisons are made between the sequence of hormonal changes and that of histological changes. In addition, questions are raised concerning the ways in which Sertoli cells are affected by experimental cryptorchidism."}
{"id": "PMID:20821", "title": "Blood-testis barrier: maintained function of inter-Sertoli cell junctions in experimental cryptorchidism in the rat, as judged by a simple lanthanum-immersion technique.", "content": "In order to elucidate the mechanisms behind the deleterious effects on the germinal epithelium of experimental cryptorchidism the hypothesis that a leaking blood-testis barrier is the cause of the damage was tested. The permeability of the specialized inter-Sertoli cell junctions to lanthanum after experimental cryptorchidism for 0.5 to 12 days was studied in the rat. In none of the time periods studied lanthanum had penetrated beyond the inter-Sertoli cell junctions. A simple lanthanum immersion technique was used. Testes of 15-days old rats (before the development of the barrier) were used as a positive control of the method, and in these testes lanthanum had penetrated up to the future lumen.", "contents": "Blood-testis barrier: maintained function of inter-Sertoli cell junctions in experimental cryptorchidism in the rat, as judged by a simple lanthanum-immersion technique. In order to elucidate the mechanisms behind the deleterious effects on the germinal epithelium of experimental cryptorchidism the hypothesis that a leaking blood-testis barrier is the cause of the damage was tested. The permeability of the specialized inter-Sertoli cell junctions to lanthanum after experimental cryptorchidism for 0.5 to 12 days was studied in the rat. In none of the time periods studied lanthanum had penetrated beyond the inter-Sertoli cell junctions. A simple lanthanum immersion technique was used. Testes of 15-days old rats (before the development of the barrier) were used as a positive control of the method, and in these testes lanthanum had penetrated up to the future lumen."}
{"id": "PMID:20824", "title": "Oxygen uptake of canine whole body and hind limb with hypocapnic alkalosis.", "content": "The effect of hypocapnic alkalosis induced by hyperventilation on whole-body and hind-limb oxygen uptake (VO2) was studied in dogs anesthetized with pentobarbital. In the intact dog with a self-perfused hind limb, increasing pHa from 7.41 to 7.58 increased whole-body VO2 8% and decreased hind-limb VO2 6%. Isolated hind limbs perfused with heparinized whole blood had similar decreases in VO2 with increases in arterial blood pH (pHa). However, isolated hind limbs perfused with whole blood containing citrate, phosphate, and dextrose (CPD) showed muscle twitches, had larger VO2 values at identical pHa's, and had an increase in VO2 with increase in pHa. These changes with a CPD perfusate were associated with low levels of ionized calcium (less than 0.5 mEq/1), disappeared when calcium ion spontaneously increased to 1.0 mEq/1, and could be prevented or abolished by the addition of calcium chloride, dantrolene, d-tubocurarine, or succinylcholine. These results are in accord with the findings of others regarding an increase in whole-body VO2 with hypocapnic alkalosis, but do not support a contributory role of skeletal muscle to the overall increase.", "contents": "Oxygen uptake of canine whole body and hind limb with hypocapnic alkalosis. The effect of hypocapnic alkalosis induced by hyperventilation on whole-body and hind-limb oxygen uptake (VO2) was studied in dogs anesthetized with pentobarbital. In the intact dog with a self-perfused hind limb, increasing pHa from 7.41 to 7.58 increased whole-body VO2 8% and decreased hind-limb VO2 6%. Isolated hind limbs perfused with heparinized whole blood had similar decreases in VO2 with increases in arterial blood pH (pHa). However, isolated hind limbs perfused with whole blood containing citrate, phosphate, and dextrose (CPD) showed muscle twitches, had larger VO2 values at identical pHa's, and had an increase in VO2 with increase in pHa. These changes with a CPD perfusate were associated with low levels of ionized calcium (less than 0.5 mEq/1), disappeared when calcium ion spontaneously increased to 1.0 mEq/1, and could be prevented or abolished by the addition of calcium chloride, dantrolene, d-tubocurarine, or succinylcholine. These results are in accord with the findings of others regarding an increase in whole-body VO2 with hypocapnic alkalosis, but do not support a contributory role of skeletal muscle to the overall increase."}
{"id": "PMID:20823", "title": "Control of gastric acidity by glycopyrrolate premedication in the parturient.", "content": "The effect of premedication with the anticholinergic quaternary ammonium compound, glycopyrrolate (0.4 mg), on gastric juice pH was investigated in 23 parturients scheduled for elective cesarean section under general anesthesia, and the results were compared to a control group of 15 nonpremedicated obstetric patients and 25 parturients premedicated with atropine (0.6 mg). In the nonpremedicated control group, the mean gastric juice pH was 2.36 (SE +/- 0.23), 66% having a pH less than the critical level of 2.5. Premedication with atropine did not significantly increase the gastric pH, while in those premedicated with glycopyrrolate, the mean pH increased to 3.7 (+/- 0.35), and the incidence of pH less than the critical level dropped to 34%. The effect of glycopyrrolate on gastric juice pH was significantly increased when the premedication-induction time was prolonged to 60 to 120 minutes. It was concluded that glycopyrrolate premedication can be used in the parturient as an additional measure to safeguard against acid-aspiration syndrome.", "contents": "Control of gastric acidity by glycopyrrolate premedication in the parturient. The effect of premedication with the anticholinergic quaternary ammonium compound, glycopyrrolate (0.4 mg), on gastric juice pH was investigated in 23 parturients scheduled for elective cesarean section under general anesthesia, and the results were compared to a control group of 15 nonpremedicated obstetric patients and 25 parturients premedicated with atropine (0.6 mg). In the nonpremedicated control group, the mean gastric juice pH was 2.36 (SE +/- 0.23), 66% having a pH less than the critical level of 2.5. Premedication with atropine did not significantly increase the gastric pH, while in those premedicated with glycopyrrolate, the mean pH increased to 3.7 (+/- 0.35), and the incidence of pH less than the critical level dropped to 34%. The effect of glycopyrrolate on gastric juice pH was significantly increased when the premedication-induction time was prolonged to 60 to 120 minutes. It was concluded that glycopyrrolate premedication can be used in the parturient as an additional measure to safeguard against acid-aspiration syndrome."}
{"id": "PMID:20828", "title": "Dirofilaria immitis and its potential mosquito vectors in central New York State.", "content": "Screening of 25,822 dog blood samples indicated approximately a 1% infection rate with Dirofilaria immitis. Dipetalonema reconditum microfilariae were found in approximately 2% of 1,876 feral dogs examined. Laboratory experimentation indicated that 6 of 10 local mosquito species examined allowed successful extrinsic incubation of D immitis. Indices of experimental infection indicated Aedes triseriatus and Anopheles quadrimaculatus were excellent hosts for D immitis, but other factors considered, Aedes vexans probably served as the primary vector of D immitis. Coquillettidia perturbans and Culex pipiens-restuans group were considered unsuitable hosts and thus unlikely vectors of canine heartworm. Natural filarial infections were found in An quadrimaculatus and Ae vexans.", "contents": "Dirofilaria immitis and its potential mosquito vectors in central New York State. Screening of 25,822 dog blood samples indicated approximately a 1% infection rate with Dirofilaria immitis. Dipetalonema reconditum microfilariae were found in approximately 2% of 1,876 feral dogs examined. Laboratory experimentation indicated that 6 of 10 local mosquito species examined allowed successful extrinsic incubation of D immitis. Indices of experimental infection indicated Aedes triseriatus and Anopheles quadrimaculatus were excellent hosts for D immitis, but other factors considered, Aedes vexans probably served as the primary vector of D immitis. Coquillettidia perturbans and Culex pipiens-restuans group were considered unsuitable hosts and thus unlikely vectors of canine heartworm. Natural filarial infections were found in An quadrimaculatus and Ae vexans."}
{"id": "PMID:20834", "title": "[Effect of tetracycline base crystallization on the conditions properties of the powders and drug forms obtained. The development of directed crystallization procedures for tetracycline base].", "content": "The study of the process of tetracycline base crystallization showed that with an increase in the rate of pH, temperature and mixed rotation changes, the specific surface of the crystalline precipitate increased with a simultaneous decrease in the bulk weight, looseness and volume density of the powder. The residual content of tetracycline in the mother solution decreased. The level of the effect of various parameters on the final results was different.", "contents": "[Effect of tetracycline base crystallization on the conditions properties of the powders and drug forms obtained. The development of directed crystallization procedures for tetracycline base]. The study of the process of tetracycline base crystallization showed that with an increase in the rate of pH, temperature and mixed rotation changes, the specific surface of the crystalline precipitate increased with a simultaneous decrease in the bulk weight, looseness and volume density of the powder. The residual content of tetracycline in the mother solution decreased. The level of the effect of various parameters on the final results was different."}
{"id": "PMID:20835", "title": "[Side effects of antibiotics in rheumatic diseases].", "content": "Complications due to antibiotic therapy in rheumatic patients subjected to season bicillin prophylaxis in Minsk within 1965--1975 and in patients with extensive collagenoses were studied. Allergic complications mainly ih the form of allergic reactions in the patients treated with bicillin-3 or picillin-5 were observed in 7.8--16.8 per cent of the patients. Within 10 years 52 cases of anaphylactic shock due to the bicillin use were recorded. Side reactions to antibiotics were observed in 16 (17.3 per cent) out of 92 patients with extensive collagenoses. For prophylaxis of the above complications it is recommended to use rational antibiotic therapy in rheumatic patients, strict registration of allergological states in the anamnesis, testing of microbial sensitivity to the antibiotics.", "contents": "[Side effects of antibiotics in rheumatic diseases]. Complications due to antibiotic therapy in rheumatic patients subjected to season bicillin prophylaxis in Minsk within 1965--1975 and in patients with extensive collagenoses were studied. Allergic complications mainly ih the form of allergic reactions in the patients treated with bicillin-3 or picillin-5 were observed in 7.8--16.8 per cent of the patients. Within 10 years 52 cases of anaphylactic shock due to the bicillin use were recorded. Side reactions to antibiotics were observed in 16 (17.3 per cent) out of 92 patients with extensive collagenoses. For prophylaxis of the above complications it is recommended to use rational antibiotic therapy in rheumatic patients, strict registration of allergological states in the anamnesis, testing of microbial sensitivity to the antibiotics."}
{"id": "PMID:20836", "title": "[Effect of the crystallization conditions of tetracycline base on the properties of the powders and drug forms obtained. The dependence of the degree of dispersion of tetracycline base on the crystallization conditions].", "content": "Characteristics of the powder dispersity of tetracycline base samples prepared by directed crystallization with variation of the process conditions were determined by the sedimentation method. It was found that the speed of the solution agitation had the maximum effect on the level and nature of the dispersity. The rate of the solution temperature and pH changing during the crystallization process had also a significant effect at low agitation speed.", "contents": "[Effect of the crystallization conditions of tetracycline base on the properties of the powders and drug forms obtained. The dependence of the degree of dispersion of tetracycline base on the crystallization conditions]. Characteristics of the powder dispersity of tetracycline base samples prepared by directed crystallization with variation of the process conditions were determined by the sedimentation method. It was found that the speed of the solution agitation had the maximum effect on the level and nature of the dispersity. The rate of the solution temperature and pH changing during the crystallization process had also a significant effect at low agitation speed."}
{"id": "PMID:20837", "title": "Conditional killing effect of staphylococcin 1580 and repair of sublethal injury in Staphylococcus aureus.", "content": "Treatment of sensitive cells with staphylococcin 1580, a bacteriocin of Staphylococcus epidermidis, rapidly induced gross changes in the permeability of the membrane. However, only a small fraction of the cells was killed when treated cells were plated on media containing low amounts of salts. Killing was greatly enhanced by increasing the amounts of small cations incorporated in the plate medium and raising the alkalinity of the medium. The effect of cations correlated inversely with the ion radius. These conditions are shown to affect the repair mechanism of the sublethally injured cells rather than the interaction of staphylococcin 1580 with the cells. A model is proposed in which the killing effect of staphylococcin 1580 is a result of the inability of cells to maintain the protonmotive force at neutral or alkaline pH as a result of the permeation of cations. Recovery of sublethal damage appears to be a complex process requiring protein and probably also ribonucleic acid synthesis and the addition of a suitable energy source.", "contents": "Conditional killing effect of staphylococcin 1580 and repair of sublethal injury in Staphylococcus aureus. Treatment of sensitive cells with staphylococcin 1580, a bacteriocin of Staphylococcus epidermidis, rapidly induced gross changes in the permeability of the membrane. However, only a small fraction of the cells was killed when treated cells were plated on media containing low amounts of salts. Killing was greatly enhanced by increasing the amounts of small cations incorporated in the plate medium and raising the alkalinity of the medium. The effect of cations correlated inversely with the ion radius. These conditions are shown to affect the repair mechanism of the sublethally injured cells rather than the interaction of staphylococcin 1580 with the cells. A model is proposed in which the killing effect of staphylococcin 1580 is a result of the inability of cells to maintain the protonmotive force at neutral or alkaline pH as a result of the permeation of cations. Recovery of sublethal damage appears to be a complex process requiring protein and probably also ribonucleic acid synthesis and the addition of a suitable energy source."}
{"id": "PMID:20838", "title": "Occurrence and distribution of bacterial indicators and pathogens in canal communities along the Texas coast.", "content": "Increased construction of residential canal communities along the southern coastline of the United States has led to a concern about their impact on water quality. Pollution of such dead-end canals is potentially hazardous because of their heavy usage for recreational activities. Coliforms, fecal coliforms, and salmonellae in the surface water and bottom sediments of six selected residential coastal canals were monitored over a period of 17 months. No statistically significant relationship was observed between the organism concentrations and temperature, pH, turbidity, and suspended solids content of water. An inverse relationship between the concentration of indicator organism and salinity of water was found, however, to occur at a 99.9% level of significance. All of the microorganisms studied were found to be present in greater numbers in sediments than in the overlying water, often by a factor of several logs. Heavy rainfall resulted in large increases in the number of organisms in both water and sediment samples. Our results indicate that bottom sediments in the shallow canal systems can act as reservoirs of enteric bacteria, which may be resuspended in response to various environmental factors and recreational activities.", "contents": "Occurrence and distribution of bacterial indicators and pathogens in canal communities along the Texas coast. Increased construction of residential canal communities along the southern coastline of the United States has led to a concern about their impact on water quality. Pollution of such dead-end canals is potentially hazardous because of their heavy usage for recreational activities. Coliforms, fecal coliforms, and salmonellae in the surface water and bottom sediments of six selected residential coastal canals were monitored over a period of 17 months. No statistically significant relationship was observed between the organism concentrations and temperature, pH, turbidity, and suspended solids content of water. An inverse relationship between the concentration of indicator organism and salinity of water was found, however, to occur at a 99.9% level of significance. All of the microorganisms studied were found to be present in greater numbers in sediments than in the overlying water, often by a factor of several logs. Heavy rainfall resulted in large increases in the number of organisms in both water and sediment samples. Our results indicate that bottom sediments in the shallow canal systems can act as reservoirs of enteric bacteria, which may be resuspended in response to various environmental factors and recreational activities."}
{"id": "PMID:20839", "title": "Development of a quantitative method for detecting enteroviruses in estuarine sediments.", "content": "Several investigators have reported on the detection of enteric viruses in marine sediments, but none determined the efficiency of their methods and only limited volumes of sediment were sampled. The purpose of this investigation was to develop a quantitative method for detecting enteroviruses in marine sediments so that their relative proportion to viruses freely suspended in estuarine water could be more accurately determined. Poliovirus was found to adsorb readily to natural marine sediments collected along the Texas Gulf coast. A number of substances were evaluated for their ability to elute adsorbed viruses. A solution of 10% fetal calf serum adjusted to pH 10.5 and 0.05M ethylenediaminetetraacetate (pH 11.0) were found to be the best eluents. Using ethylenediaminetetraacetate as an eluent, it was possible to elute virus from large volumes of sediment and reconcentrate the sediment eluate into an economically assayable volume (30 to 50 ml). Poliovirus could be recovered from the sediment with an overall efficiency of 50%. This method was found to be satisfactory for the recovery of naturally occurring animal viruses in estuarine sediments from the upper Texas Gulf coast.", "contents": "Development of a quantitative method for detecting enteroviruses in estuarine sediments. Several investigators have reported on the detection of enteric viruses in marine sediments, but none determined the efficiency of their methods and only limited volumes of sediment were sampled. The purpose of this investigation was to develop a quantitative method for detecting enteroviruses in marine sediments so that their relative proportion to viruses freely suspended in estuarine water could be more accurately determined. Poliovirus was found to adsorb readily to natural marine sediments collected along the Texas Gulf coast. A number of substances were evaluated for their ability to elute adsorbed viruses. A solution of 10% fetal calf serum adjusted to pH 10.5 and 0.05M ethylenediaminetetraacetate (pH 11.0) were found to be the best eluents. Using ethylenediaminetetraacetate as an eluent, it was possible to elute virus from large volumes of sediment and reconcentrate the sediment eluate into an economically assayable volume (30 to 50 ml). Poliovirus could be recovered from the sediment with an overall efficiency of 50%. This method was found to be satisfactory for the recovery of naturally occurring animal viruses in estuarine sediments from the upper Texas Gulf coast."}
{"id": "PMID:20840", "title": "Production of beta-galactosidase from Streptococcus thermophilus grown in whey.", "content": "beta-D-Galactosidase (EC 3.2.1.23) was extracted from Streptococcus thermophilus grown in deproteinized cheese whey. Cultural conditions optimum for maximum enzyme production were pH 7.0, 40 degrees C, and 24 h. Proteose peptone (2.0%, wt/vol) and corn steep liquor (2.8%, wt/vol) were highly stimulatory, increasing the enzyme units available in their absence from 660 U/liter of medium to 18,200 and 10,000 U/liter of medium, respectively, in their presence. There was an insignificant increase in the production of enzyme in the presence of added inorganic nitrogen and phosphorus sources. Enzymatic hydrolysis for recuction of lactose content in aqueous solution and in skim milk was studied.", "contents": "Production of beta-galactosidase from Streptococcus thermophilus grown in whey. beta-D-Galactosidase (EC 3.2.1.23) was extracted from Streptococcus thermophilus grown in deproteinized cheese whey. Cultural conditions optimum for maximum enzyme production were pH 7.0, 40 degrees C, and 24 h. Proteose peptone (2.0%, wt/vol) and corn steep liquor (2.8%, wt/vol) were highly stimulatory, increasing the enzyme units available in their absence from 660 U/liter of medium to 18,200 and 10,000 U/liter of medium, respectively, in their presence. There was an insignificant increase in the production of enzyme in the presence of added inorganic nitrogen and phosphorus sources. Enzymatic hydrolysis for recuction of lactose content in aqueous solution and in skim milk was studied."}
{"id": "PMID:20854", "title": "Scleroderma-like changes in chronic graft vs host disease.", "content": "A case of chronic graft vs host disease had scleroderma-like skin changes. Clinical progression was from poikiloderma to scleroderma, and histopathological changes and results of direct immunofluorescence were noted. It is probable that both cell-mediated (T-cell) and humoral (B-cell) mechanisms contribute to the pathogenesis of the graft vs host reaction.", "contents": "Scleroderma-like changes in chronic graft vs host disease. A case of chronic graft vs host disease had scleroderma-like skin changes. Clinical progression was from poikiloderma to scleroderma, and histopathological changes and results of direct immunofluorescence were noted. It is probable that both cell-mediated (T-cell) and humoral (B-cell) mechanisms contribute to the pathogenesis of the graft vs host reaction."}
{"id": "PMID:20856", "title": "Long-term esophageal function following repair of esophageal atresia.", "content": "Primary repair of esophageal atresia restores gastrointestinal continuity, but does not ensure normal esophageal function. To date 22 patients, six to 32 (average 15) years after repair of their esophageal atresias, have been evaluated by personal interview and esophageal manometrics and acid reflux testing. Previous barium swallow examinations had demonstrated varying degrees of anastomotic narrowing (12 patients), abnormal esophageal motor function (11 patients), gastroesophageal reflux (two patients), and hiatal hernia (one patient). Ten patients experience intermittent dysphagia for solid foods. Seven have typical symptoms of gastroesophageal reflux. Esophageal function tests including manometry and intraesophageal pH recording, have demonstrated varying abnormalities of esophageal motility in 21 patients and moderate to severe gastroesophageal reflux in 13. Two patients have required reconstruction of the esophagogastric junction for control of severe reflux esophagitis. The unexpected high incidence of gastroesophageal reflux in these patients, coupled with their abnormal esophageal motility which impairs normal acid clearing, renders them more prone to reflux esophagitis. Careful long-term evaluation for gastroesophageal reflux and its complications is indicated following primary repair of esophageal atresia. Evaluation of esophageal function with intraesophageal pressure and pH recordings is a far more sensitive indicator of esophageal physiology than the barium swallow examination.", "contents": "Long-term esophageal function following repair of esophageal atresia. Primary repair of esophageal atresia restores gastrointestinal continuity, but does not ensure normal esophageal function. To date 22 patients, six to 32 (average 15) years after repair of their esophageal atresias, have been evaluated by personal interview and esophageal manometrics and acid reflux testing. Previous barium swallow examinations had demonstrated varying degrees of anastomotic narrowing (12 patients), abnormal esophageal motor function (11 patients), gastroesophageal reflux (two patients), and hiatal hernia (one patient). Ten patients experience intermittent dysphagia for solid foods. Seven have typical symptoms of gastroesophageal reflux. Esophageal function tests including manometry and intraesophageal pH recording, have demonstrated varying abnormalities of esophageal motility in 21 patients and moderate to severe gastroesophageal reflux in 13. Two patients have required reconstruction of the esophagogastric junction for control of severe reflux esophagitis. The unexpected high incidence of gastroesophageal reflux in these patients, coupled with their abnormal esophageal motility which impairs normal acid clearing, renders them more prone to reflux esophagitis. Careful long-term evaluation for gastroesophageal reflux and its complications is indicated following primary repair of esophageal atresia. Evaluation of esophageal function with intraesophageal pressure and pH recordings is a far more sensitive indicator of esophageal physiology than the barium swallow examination."}
{"id": "PMID:20857", "title": "Interaction of drugs with apomorphine, tryptamine and norepinephrine. A new 'in vivo' approach: the ATN-test in rats.", "content": "A new experimental test procedure is described for the 'in vivo' study of drug interactions with dopamine (DA), 5 hydroxy-tryptamine (5-HT) and norepinephrine (NE). The ultimate aim of this study is to provide an empirical evaluation of the relative specificity with which drugs may affect particular neurotransmitter systems, and to allow a classification of new drugs in this respect. The data indicate that, within certain dosage limits, compounds may modulate specifically a single component of the test procedure and may thus be considered as interacting specifically to modify one neurotransmitter system: i.e. DA in the apomorphine-test (e.g. pimozide), 5-HT in the tryptamine-test (e.g. pizotifen) and NE in the norepinephrine-test (e.g. phenoxy-benzamine). Higher doses of the same compounds may, however, excert effects on other neurotransmitter systems as well, and these actions may be classified as nonspecific. Thus the concept of drug specificity as applied in the present study, is not exclusive, but refers to the dissociation, in terms of doses, which exists between a drug's effect on one neurotransmitter system and its possible effects on other systems. The ATN-test separates and delineates, in terms of doses, the specific and nonspecific effects of drugs.", "contents": "Interaction of drugs with apomorphine, tryptamine and norepinephrine. A new 'in vivo' approach: the ATN-test in rats. A new experimental test procedure is described for the 'in vivo' study of drug interactions with dopamine (DA), 5 hydroxy-tryptamine (5-HT) and norepinephrine (NE). The ultimate aim of this study is to provide an empirical evaluation of the relative specificity with which drugs may affect particular neurotransmitter systems, and to allow a classification of new drugs in this respect. The data indicate that, within certain dosage limits, compounds may modulate specifically a single component of the test procedure and may thus be considered as interacting specifically to modify one neurotransmitter system: i.e. DA in the apomorphine-test (e.g. pimozide), 5-HT in the tryptamine-test (e.g. pizotifen) and NE in the norepinephrine-test (e.g. phenoxy-benzamine). Higher doses of the same compounds may, however, excert effects on other neurotransmitter systems as well, and these actions may be classified as nonspecific. Thus the concept of drug specificity as applied in the present study, is not exclusive, but refers to the dissociation, in terms of doses, which exists between a drug's effect on one neurotransmitter system and its possible effects on other systems. The ATN-test separates and delineates, in terms of doses, the specific and nonspecific effects of drugs."}
{"id": "PMID:20858", "title": "Cilioinhibitory effect of phenothiazines in vitro and its antagonism by Ca++.", "content": "The inhibition of ciliary beating in vitro by physiologic concentrations of chlorpromazine (CPZ) and prochlorperazine (PCP) was demonstrated in two experimental systems. CPZ had a greater cilioinhibitory effect than PCP on the rotational velocity of tissue explants from the frog palate in amphibian Ringers, and on the frequency of ciliary beating in rat tracheal rings in culture medium. Addition of calcium acetate in equal molarity to CPZ, within a time limit dependent on the drug concentration, reversed this inhibition, while dibutyryl cyclic AMP did not. Simultaneous addition of Ca++ and CPZ slowed down, but did not stop, this ciliostasis, while priming with Ca++ or cyclic AMP prior to drug addition had less of an effect. These data lend support to a prevalent theory that CPZ exerts its actions by displacing calcium ions from membrane sites.", "contents": "Cilioinhibitory effect of phenothiazines in vitro and its antagonism by Ca++. The inhibition of ciliary beating in vitro by physiologic concentrations of chlorpromazine (CPZ) and prochlorperazine (PCP) was demonstrated in two experimental systems. CPZ had a greater cilioinhibitory effect than PCP on the rotational velocity of tissue explants from the frog palate in amphibian Ringers, and on the frequency of ciliary beating in rat tracheal rings in culture medium. Addition of calcium acetate in equal molarity to CPZ, within a time limit dependent on the drug concentration, reversed this inhibition, while dibutyryl cyclic AMP did not. Simultaneous addition of Ca++ and CPZ slowed down, but did not stop, this ciliostasis, while priming with Ca++ or cyclic AMP prior to drug addition had less of an effect. These data lend support to a prevalent theory that CPZ exerts its actions by displacing calcium ions from membrane sites."}
{"id": "PMID:20855", "title": "pH effects on ciliomotility and morphology of respiratory mucosa.", "content": "Tracheal cilia of cows exposed, in vitro, for 20 hours to different acidities and alkalinities of sulfuric acid and sodium hydroxide, respectively, showed ciliomotility at pH values as low as 4.9, while the epithelial cells began to be expelled from the mucosa at pH 6.7, initiating a reduction of ciliary function around this pH value. In alkaline reactions, ciliostasis occurred at pH 9.76. Destroyed cilia were found above pH 10.15, while they were morphologically unchanged at pH values as low as 4.0, the lowest value examined. The first symptoms, however, of adverse effects were intracellular edema and the simultaneous occurrence of cellular polyps in both acid and alkaline reactions at pH 6.7 and 9.5, respectively. The results indicate that the early effects of air pollutants are better demonstrated by transmission electron microscopy studies than by, e.g., studies of ciliomotility.", "contents": "pH effects on ciliomotility and morphology of respiratory mucosa. Tracheal cilia of cows exposed, in vitro, for 20 hours to different acidities and alkalinities of sulfuric acid and sodium hydroxide, respectively, showed ciliomotility at pH values as low as 4.9, while the epithelial cells began to be expelled from the mucosa at pH 6.7, initiating a reduction of ciliary function around this pH value. In alkaline reactions, ciliostasis occurred at pH 9.76. Destroyed cilia were found above pH 10.15, while they were morphologically unchanged at pH values as low as 4.0, the lowest value examined. The first symptoms, however, of adverse effects were intracellular edema and the simultaneous occurrence of cellular polyps in both acid and alkaline reactions at pH 6.7 and 9.5, respectively. The results indicate that the early effects of air pollutants are better demonstrated by transmission electron microscopy studies than by, e.g., studies of ciliomotility."}
{"id": "PMID:20861", "title": "Studies on the cell cycle of Myxobacter AL-1. II. Activities of seven enzymes during the cell cycle.", "content": "The properties of seven enzymes were studied in extracts from Myxobacter AL-1. The enzymes were isocitrate dehydrogenase (E.C.1.1.1.42), succinate dehydrogenase (E.C.1.3.99.1), alkaline phosphatase (E.C.3.1.3.1), alpha-glucosidase (E.C.3.2.1.20), beta-glucosidase (E.C.3.2.1.21), beta-galactosidase (E.C.3.2.1.23), and N-acetyl-glucosaminidase (E.C. 3.2.1.30). Four of these enzymes: isocitrate dehydrogenase, alpha-glucosidase, beta-glucosidase, and beta-galactosidase are cytosolic enzymes. Succinate dehydrogenase was found to be located on the cytoplasmic membrane system, whereas alkaline phosphatase and N-acetylglucosaminidase were considered as enzymes which bind the outer membranes resp. the cell wall. During the cell cycle, all enzymes have a pattern of discontinuous activity increase. Succinate dehydrogenase and isocitrate dehydrogenase exhibit a stepwise increase of activity, whereas the other enzymes follow the pattern of a peak enzyme.", "contents": "Studies on the cell cycle of Myxobacter AL-1. II. Activities of seven enzymes during the cell cycle. The properties of seven enzymes were studied in extracts from Myxobacter AL-1. The enzymes were isocitrate dehydrogenase (E.C.1.1.1.42), succinate dehydrogenase (E.C.1.3.99.1), alkaline phosphatase (E.C.3.1.3.1), alpha-glucosidase (E.C.3.2.1.20), beta-glucosidase (E.C.3.2.1.21), beta-galactosidase (E.C.3.2.1.23), and N-acetyl-glucosaminidase (E.C. 3.2.1.30). Four of these enzymes: isocitrate dehydrogenase, alpha-glucosidase, beta-glucosidase, and beta-galactosidase are cytosolic enzymes. Succinate dehydrogenase was found to be located on the cytoplasmic membrane system, whereas alkaline phosphatase and N-acetylglucosaminidase were considered as enzymes which bind the outer membranes resp. the cell wall. During the cell cycle, all enzymes have a pattern of discontinuous activity increase. Succinate dehydrogenase and isocitrate dehydrogenase exhibit a stepwise increase of activity, whereas the other enzymes follow the pattern of a peak enzyme."}
{"id": "PMID:20862", "title": "Dependence of sulphate uptake by Anacystis nidulans on energy, on osmotic shock and on sulphate stravation.", "content": "Sulphate uptake by Anacystis nidulans under aerobic conditions in the light was found to be sensitive to metabolic poisons, such as N,N'-dicyclohexylcarbodiimide and carbonyl cyanide m-chlorophenyl hydrazone. It was also depressed by darkness. The sulphate absorption is an energy-dependent process. Sulphate uptake was also inhibited by chromate and selenate. Osmotic shock strongly affected sulphate uptake. This effect could be interpreted by a loss of a binding protein involved in the absorption of sulphate. Osmotic shock also depressed oxygen production in light and oxygen consumption in darkness; however, shocked cells were able to grow normally. Sulphate uptake was strongly enhanced by sulphate starvation, but this enhancement was partly prevented by chloramphenicol. Apparently sulphate starvation depressed the synthesis of a carrier involved in the transport of sulphate. During sulphate starvation the membrane potential, measured by the uptake of triphenylmethylphosphonium, increases. This may be due to changes in the membrane.", "contents": "Dependence of sulphate uptake by Anacystis nidulans on energy, on osmotic shock and on sulphate stravation. Sulphate uptake by Anacystis nidulans under aerobic conditions in the light was found to be sensitive to metabolic poisons, such as N,N'-dicyclohexylcarbodiimide and carbonyl cyanide m-chlorophenyl hydrazone. It was also depressed by darkness. The sulphate absorption is an energy-dependent process. Sulphate uptake was also inhibited by chromate and selenate. Osmotic shock strongly affected sulphate uptake. This effect could be interpreted by a loss of a binding protein involved in the absorption of sulphate. Osmotic shock also depressed oxygen production in light and oxygen consumption in darkness; however, shocked cells were able to grow normally. Sulphate uptake was strongly enhanced by sulphate starvation, but this enhancement was partly prevented by chloramphenicol. Apparently sulphate starvation depressed the synthesis of a carrier involved in the transport of sulphate. During sulphate starvation the membrane potential, measured by the uptake of triphenylmethylphosphonium, increases. This may be due to changes in the membrane."}
{"id": "PMID:20863", "title": "The effect of inorganic phosphate on cyanogenesis by Pseudomonas aeruginosa.", "content": "The biosynthesis of hydrogen cyanide (HCN) by a strain of Pseudomonas aeruginosa is found to be significantly influenced by inorganic phosphate. Optimum HCN production occurs when the phosphate concentration is between 1 and 10 mM. Above and below this concentration the amount of HCN produced decreases sharply and at 0.1 and 100 mM phosphate low HCN production occurs. If a culture growing at 0.1 mM phosphate and producing low HCN is shifted to 10 mM phosphate, HCN biosynthesis resumes. Experiments with chloramphenicol indicate that de novo-protein synthesis is required for the process.", "contents": "The effect of inorganic phosphate on cyanogenesis by Pseudomonas aeruginosa. The biosynthesis of hydrogen cyanide (HCN) by a strain of Pseudomonas aeruginosa is found to be significantly influenced by inorganic phosphate. Optimum HCN production occurs when the phosphate concentration is between 1 and 10 mM. Above and below this concentration the amount of HCN produced decreases sharply and at 0.1 and 100 mM phosphate low HCN production occurs. If a culture growing at 0.1 mM phosphate and producing low HCN is shifted to 10 mM phosphate, HCN biosynthesis resumes. Experiments with chloramphenicol indicate that de novo-protein synthesis is required for the process."}
{"id": "PMID:20864", "title": "The role of vanadium in gree plants. II. Vanadium in green algae--two sites of action.", "content": "Cells of Chlorella pyrenoidosa, derived from vanadium free agar slants, respond with great sensitivity to microamounts of vanadium, added as NH4VO3 to autotrophic liquid cultures. Between 0.01 and 1 microgram V per litre nutrient medium (2-10(-10)-2-10(-8) g-at/1), the algae respond with a continuous incrase in dry weight. At higher V-concentrations, further enhancement in biomass is accompanied by a additional increase in chlorophyll content. Maximum V-effect on both parameters was found to be at 500 microgram V/1 (10(-5) G-AT/1). Dry weight as well as chlorophyll content of Chlorella are decreased by concentrations above 25 mg V/1; 100 mg V/1 (2-10(-3) g-at/1) stop growth and cause death of the cells. The toxic threshold for the V-content in the algae was determined to be at 150-200 microgram V/g (3-4-10(-6) g-at/g) dry weight. Two different pH-optima for a positive vanadium action on dry weight and chlorophyll biosynthesis were established, the first at pH 7, the other in the range pH 7.5--8. Two sites of vanadium action in green algae are discussed.", "contents": "The role of vanadium in gree plants. II. Vanadium in green algae--two sites of action. Cells of Chlorella pyrenoidosa, derived from vanadium free agar slants, respond with great sensitivity to microamounts of vanadium, added as NH4VO3 to autotrophic liquid cultures. Between 0.01 and 1 microgram V per litre nutrient medium (2-10(-10)-2-10(-8) g-at/1), the algae respond with a continuous incrase in dry weight. At higher V-concentrations, further enhancement in biomass is accompanied by a additional increase in chlorophyll content. Maximum V-effect on both parameters was found to be at 500 microgram V/1 (10(-5) G-AT/1). Dry weight as well as chlorophyll content of Chlorella are decreased by concentrations above 25 mg V/1; 100 mg V/1 (2-10(-3) g-at/1) stop growth and cause death of the cells. The toxic threshold for the V-content in the algae was determined to be at 150-200 microgram V/g (3-4-10(-6) g-at/g) dry weight. Two different pH-optima for a positive vanadium action on dry weight and chlorophyll biosynthesis were established, the first at pH 7, the other in the range pH 7.5--8. Two sites of vanadium action in green algae are discussed."}
{"id": "PMID:20865", "title": "Alpha-isopropylmalate synthase from Alcaligenes eutrophus H 16. III. Endproduct inhibition and its relief by valine and isoleucine.", "content": "The alpha-isopropylmalate synthase (EC 4.1.3.12) from Alcaligenes eutrophus H 16 was inhibited by L-leucine and alpha-ketoisocaproate. The extent of inhibition was influenced by substrate- and inhibitor concentrations as well as by the pH. Intermediary plateaus, which always appeared in the inhibition curves, suggested cooperative effects. The maximal Hill coefficient was found to be two. At low concentrations of leucine the inhibition mechanism was of the competitive type with respect to substrate acetyl coenzyme A and of the noncompetitive type with respect to substrate alpha-ketoisovalerate. The inhibition was specifically relieved by the addition of valine or isoleucine. The anomalous effect of temperature on enzyme activity was diminished by leucine. The Arrhenius energy of the reaction increased from about 11 kcal/mole in the absence of leucine to about 18 kcal/mole in the presence of leucine. The further addition of valine reversed this effect. The physiological relevance of the alpha-ketoisocaproate-mediated inhibition is discussed.", "contents": "Alpha-isopropylmalate synthase from Alcaligenes eutrophus H 16. III. Endproduct inhibition and its relief by valine and isoleucine. The alpha-isopropylmalate synthase (EC 4.1.3.12) from Alcaligenes eutrophus H 16 was inhibited by L-leucine and alpha-ketoisocaproate. The extent of inhibition was influenced by substrate- and inhibitor concentrations as well as by the pH. Intermediary plateaus, which always appeared in the inhibition curves, suggested cooperative effects. The maximal Hill coefficient was found to be two. At low concentrations of leucine the inhibition mechanism was of the competitive type with respect to substrate acetyl coenzyme A and of the noncompetitive type with respect to substrate alpha-ketoisovalerate. The inhibition was specifically relieved by the addition of valine or isoleucine. The anomalous effect of temperature on enzyme activity was diminished by leucine. The Arrhenius energy of the reaction increased from about 11 kcal/mole in the absence of leucine to about 18 kcal/mole in the presence of leucine. The further addition of valine reversed this effect. The physiological relevance of the alpha-ketoisocaproate-mediated inhibition is discussed."}
{"id": "PMID:20866", "title": "An NADP-linked acetoacetyl CoA reductase from Zoogloea ramigera.", "content": "Zoogloea ramigera I-16 M was found to contain two stereospecific acetoacetyl CoA reductases; one was NADP+-linked and D(-)-beta-hydroxybutyryl CoA specific and the other was NAD+-linked and L(+)-isomer specific. The NADP+-linked enzyme, purified approximately 150-fold, had a pH optimum for the reduction of acetoacetyl CoA at 8.1, but no definite pH optimum for the oxidation for beta-hydroxybutyryl CoA. The apparent Michaelis constants for acetoacetyl CoA and NADPH were 8.3 and 21 micrometer, respectively. The enzyme was markedly inhibited by acetoacetyl CoA at concentrations higher than 10 micrometer. The incorporation of [1-14C]acetyl CoA into poly-beta-hydroxybutyrate (PHB) by bacterial crude extract (containing beta-ketothiolase, acetoacetyl CoA reductases, enoyl CoA hydratases and PHB synthases) or by a system reconstituted from purified preparations of beta-ketothiolase, acetoacetyl CoA reductase and PHB synthase, was observed only in the presence of NADPH, but not NADH. Among various enzymes involved in PHB metabolism, only the specific activity of glucose 6-phosphate dehydrogenase was elevated 5-fold within 2 h after the addition of glucose to the cells grown in the basal medium. These findings suggest that, in Z. ramigera I-16M, acetoacetyl CoA is directly reduced to D(-)-beta-hydroxybutyryl CoA by the NADP+-dependent reductase, and PHB synthesis is at least partially controled by NADPH availability through glucose 6-phosphate dehydrogenase.", "contents": "An NADP-linked acetoacetyl CoA reductase from Zoogloea ramigera. Zoogloea ramigera I-16 M was found to contain two stereospecific acetoacetyl CoA reductases; one was NADP+-linked and D(-)-beta-hydroxybutyryl CoA specific and the other was NAD+-linked and L(+)-isomer specific. The NADP+-linked enzyme, purified approximately 150-fold, had a pH optimum for the reduction of acetoacetyl CoA at 8.1, but no definite pH optimum for the oxidation for beta-hydroxybutyryl CoA. The apparent Michaelis constants for acetoacetyl CoA and NADPH were 8.3 and 21 micrometer, respectively. The enzyme was markedly inhibited by acetoacetyl CoA at concentrations higher than 10 micrometer. The incorporation of [1-14C]acetyl CoA into poly-beta-hydroxybutyrate (PHB) by bacterial crude extract (containing beta-ketothiolase, acetoacetyl CoA reductases, enoyl CoA hydratases and PHB synthases) or by a system reconstituted from purified preparations of beta-ketothiolase, acetoacetyl CoA reductase and PHB synthase, was observed only in the presence of NADPH, but not NADH. Among various enzymes involved in PHB metabolism, only the specific activity of glucose 6-phosphate dehydrogenase was elevated 5-fold within 2 h after the addition of glucose to the cells grown in the basal medium. These findings suggest that, in Z. ramigera I-16M, acetoacetyl CoA is directly reduced to D(-)-beta-hydroxybutyryl CoA by the NADP+-dependent reductase, and PHB synthesis is at least partially controled by NADPH availability through glucose 6-phosphate dehydrogenase."}
{"id": "PMID:20867", "title": "Prostaglandins. A review of neurophysiology and psychiatric implications.", "content": "This article reviews the function of prostaglandins (PGs) in the nervous system and discusses the possible alterations in PG metabolism as relating to mental illness. The PGs are a unique group of cyclic fatty acids whose immediate precursors are thought to function postsynaptically by inhibition or facillitation of neurotransmission through cyclase inhibition or activation, and by means of a negative feedback loop to inhibit further release of neurotransmitter from the presynaptic nerve. A review of PGs in psychiatric conditions is presented as well as a discussion of the interaction of psychoactive drugs with the PGs. The concluding section of this review discusses possible future strategies to provide insight into PG physiology as it relates to synaptic transmission in normal and pathological conditions in man.", "contents": "Prostaglandins. A review of neurophysiology and psychiatric implications. This article reviews the function of prostaglandins (PGs) in the nervous system and discusses the possible alterations in PG metabolism as relating to mental illness. The PGs are a unique group of cyclic fatty acids whose immediate precursors are thought to function postsynaptically by inhibition or facillitation of neurotransmission through cyclase inhibition or activation, and by means of a negative feedback loop to inhibit further release of neurotransmitter from the presynaptic nerve. A review of PGs in psychiatric conditions is presented as well as a discussion of the interaction of psychoactive drugs with the PGs. The concluding section of this review discusses possible future strategies to provide insight into PG physiology as it relates to synaptic transmission in normal and pathological conditions in man."}
{"id": "PMID:20868", "title": "[On the toxicology of carbromal. II. Pharmacokinetics of carbromal and its hypnotically active metabolites in the rat (author's transl)].", "content": "Oral doses up to 20 mg/kg of carbromal and of bromoethylbutyramide were rapidly absorbed in the rat. Absorption from the stomach ligated at the pyloric end was 5-8 fold less than absorption of carbromal injected directly into the small intestine. Oral doses greater than 20 mg/kg of carbromal disappeared more slowly from the gastro-intestinal tract because gastric emptying was delayed. Both carbromal and bromoethylbutyramide were able to reduce the basal tone and the acetylcholine-induced contraction of isolated rat fundus strips. Carbromal and bromoethylbutyramide distributed evenly between serum, brain and skeletal muscle. Concentrations in adipose tissue were three times those in the other three tissues. Concentrations of both carbromal and of bromoethylbutyramide in all four tissues declined at the same rate. Thus, serum concentration of either compound may be used to estimate the total body content. Intraperitoneally injected carbromal, bromoethylbutyramide and ethylbutyrylurea disappeared from the brain and from the serum with half-life of 3-4 h and 5-7 h, respectively. Traces only of unchanged carbromal, bromoethylbutyramide, or ethylbutyrylurea were excreted with urine or feces indicating rapid and extensive biotransformation of the three compounds in this species. No evidence was obtained of secretion of either carbromal or its two metabolites into the lumen of the stomach. The findings are discussed as to their relevance for acute carbromal poisoning in humans.", "contents": "[On the toxicology of carbromal. II. Pharmacokinetics of carbromal and its hypnotically active metabolites in the rat (author's transl)]. Oral doses up to 20 mg/kg of carbromal and of bromoethylbutyramide were rapidly absorbed in the rat. Absorption from the stomach ligated at the pyloric end was 5-8 fold less than absorption of carbromal injected directly into the small intestine. Oral doses greater than 20 mg/kg of carbromal disappeared more slowly from the gastro-intestinal tract because gastric emptying was delayed. Both carbromal and bromoethylbutyramide were able to reduce the basal tone and the acetylcholine-induced contraction of isolated rat fundus strips. Carbromal and bromoethylbutyramide distributed evenly between serum, brain and skeletal muscle. Concentrations in adipose tissue were three times those in the other three tissues. Concentrations of both carbromal and of bromoethylbutyramide in all four tissues declined at the same rate. Thus, serum concentration of either compound may be used to estimate the total body content. Intraperitoneally injected carbromal, bromoethylbutyramide and ethylbutyrylurea disappeared from the brain and from the serum with half-life of 3-4 h and 5-7 h, respectively. Traces only of unchanged carbromal, bromoethylbutyramide, or ethylbutyrylurea were excreted with urine or feces indicating rapid and extensive biotransformation of the three compounds in this species. No evidence was obtained of secretion of either carbromal or its two metabolites into the lumen of the stomach. The findings are discussed as to their relevance for acute carbromal poisoning in humans."}
{"id": "PMID:20869", "title": "Separation and quantitative determination of acecarbromal, carbromal, and bromisoval as well as their main metabolites by means of high-pressure liquid chromatographic analysis.", "content": "A method is described to separate and quantitatively determine bromoureides and their bromo- and non-bromo-metabolites by means of high-pressure liquid chromatography. This method allows simultaneous measurement of these substances after intake of therapeutic as well as toxic doses.", "contents": "Separation and quantitative determination of acecarbromal, carbromal, and bromisoval as well as their main metabolites by means of high-pressure liquid chromatographic analysis. A method is described to separate and quantitatively determine bromoureides and their bromo- and non-bromo-metabolites by means of high-pressure liquid chromatography. This method allows simultaneous measurement of these substances after intake of therapeutic as well as toxic doses."}
{"id": "PMID:20870", "title": "Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.", "content": "Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed.", "contents": "Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey. Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed."}
{"id": "PMID:20874", "title": "Serotypes of pneumococci in pneumonia, meningitis and other pneumococcal infections.", "content": "During a five-year period, 1965 to 1969 inclusive, pneumococci from 294 patients with acute pneumococcal infections were serotyped. Pneumococci of 33 serotypes were encountered, of which types 3 and 19 were most frequent. The spectrum of infections included pneumonia, meningitis, peritonitis, otitis media and mastoiditis, wound infection and conjuctivitis. At least 17 infections were fatal, all of which, with one exception, occurred either in infants or in adults over 50 years of age. In pneumonia, type 3 pneumococcus was predominant, being isolated from 21 of 101 patients. In 67 cases of pneumococcal meningitis, most of which were in children, the commonest type was 14. If a pneumococcal vaccine is produced for use in Australia, inclusion of serotypes 1, 3, 4, 6, 9, 14, 19 and 23 should be considered. These eight types caused 52% of the cases of pneumonia and 67% of the cases of meningitis in this study.", "contents": "Serotypes of pneumococci in pneumonia, meningitis and other pneumococcal infections. During a five-year period, 1965 to 1969 inclusive, pneumococci from 294 patients with acute pneumococcal infections were serotyped. Pneumococci of 33 serotypes were encountered, of which types 3 and 19 were most frequent. The spectrum of infections included pneumonia, meningitis, peritonitis, otitis media and mastoiditis, wound infection and conjuctivitis. At least 17 infections were fatal, all of which, with one exception, occurred either in infants or in adults over 50 years of age. In pneumonia, type 3 pneumococcus was predominant, being isolated from 21 of 101 patients. In 67 cases of pneumococcal meningitis, most of which were in children, the commonest type was 14. If a pneumococcal vaccine is produced for use in Australia, inclusion of serotypes 1, 3, 4, 6, 9, 14, 19 and 23 should be considered. These eight types caused 52% of the cases of pneumonia and 67% of the cases of meningitis in this study."}
{"id": "PMID:20876", "title": "Potassium ion-activated hydrolysis of p-nitrophenyl phosphate in pancreatic islet-cell membranes.", "content": "Hydrolysis of p-nitrophenyl phosphate was measured in a fraction enriched in plasma membranes from pancreatic islets of non-inbred ob/ob mice. Hydrolysis was stimulated by K+ (10mM) in the pH range 5--10; a small peak of K+-induced activation was observed between pH7.5 and 8. Both the K+-induced activation and the hydrolysis in the absence of K+ were Mg2+-dependent; maximum activation was obtained with 10mM-K+ plus 5 mM-Mg2+. Rb+ was as effective an activator as K+. Ouabain was inhibitory, the effect being inversely related to the K+ concentration; 0.1--0.2mM-ouabain caused about 50% inhibition in the presence of 1 mM-K+, but had no demonstrable effect in the presence of 4--5mM-K+. The K+-stimulated activity was markedly inhibited by 0.1mM-ATP, 35--140 MM-Na+, or 0.01 mM-p-chloromercuribenzenesulphonic acid. Similarities to Rb+ accumulation suggest that catalysis of univalent cation flow in pancreatic beta-cells may be coupled to a phosphoryl-transfer reaction with ATP as natural substrate or regulator.", "contents": "Potassium ion-activated hydrolysis of p-nitrophenyl phosphate in pancreatic islet-cell membranes. Hydrolysis of p-nitrophenyl phosphate was measured in a fraction enriched in plasma membranes from pancreatic islets of non-inbred ob/ob mice. Hydrolysis was stimulated by K+ (10mM) in the pH range 5--10; a small peak of K+-induced activation was observed between pH7.5 and 8. Both the K+-induced activation and the hydrolysis in the absence of K+ were Mg2+-dependent; maximum activation was obtained with 10mM-K+ plus 5 mM-Mg2+. Rb+ was as effective an activator as K+. Ouabain was inhibitory, the effect being inversely related to the K+ concentration; 0.1--0.2mM-ouabain caused about 50% inhibition in the presence of 1 mM-K+, but had no demonstrable effect in the presence of 4--5mM-K+. The K+-stimulated activity was markedly inhibited by 0.1mM-ATP, 35--140 MM-Na+, or 0.01 mM-p-chloromercuribenzenesulphonic acid. Similarities to Rb+ accumulation suggest that catalysis of univalent cation flow in pancreatic beta-cells may be coupled to a phosphoryl-transfer reaction with ATP as natural substrate or regulator."}
{"id": "PMID:20899", "title": "[Determination of the KM-value of the fumarase (E.C. 4.2.1.2) with bencyclan-hydrogenfumarate as the substrate (author's transl)].", "content": "The Michaelis-Menten constant for fumarase (E.C. 4.2.1.2) has been determined by measuring the enzyme activity by the spectrophotometric method of Racker, which depends on the formation or disappearance of the double bond of fumaric acid. When using Na2-fumarate or bencyclan hydrogenfumarate (Fludilat), respectively, as a substrate, a KM-value of 1.3 X 10(-3) M was found for both substances. In a linked assay where the formation of NADH in the reaction of fumarate leads to malate leads to oxaloacetate was used as a parameter for the reaction rate, a KM-value of 1.35 X 10(-3) M was found.", "contents": "[Determination of the KM-value of the fumarase (E.C. 4.2.1.2) with bencyclan-hydrogenfumarate as the substrate (author's transl)]. The Michaelis-Menten constant for fumarase (E.C. 4.2.1.2) has been determined by measuring the enzyme activity by the spectrophotometric method of Racker, which depends on the formation or disappearance of the double bond of fumaric acid. When using Na2-fumarate or bencyclan hydrogenfumarate (Fludilat), respectively, as a substrate, a KM-value of 1.3 X 10(-3) M was found for both substances. In a linked assay where the formation of NADH in the reaction of fumarate leads to malate leads to oxaloacetate was used as a parameter for the reaction rate, a KM-value of 1.35 X 10(-3) M was found."}
{"id": "PMID:20900", "title": "Effects of clozapine and other dibenzo-epines on central dopaminergic and cholinergic systems. Structure-activity relationships.", "content": "Structure-activity relationships of 16 dibenzoepines, including clozapine, loxapine, clothiapine and perlapine, have been investigated with regard to locomotor inhibition, cataleptogenesis, apomorphine antagonism, arousal inhibition, effect on striatal dopamine metabolism, and in vivo and in vitro anticholinergic potency. Thioridazine and the classical neuroleptics haloperidol and chlorpromazine were included in the study for comparison. The classical tests used to detect neuroleptic activity in laboratory animals were found to be poor predictors of possible clinical effectiveness of the dibenzo-epines.", "contents": "Effects of clozapine and other dibenzo-epines on central dopaminergic and cholinergic systems. Structure-activity relationships. Structure-activity relationships of 16 dibenzoepines, including clozapine, loxapine, clothiapine and perlapine, have been investigated with regard to locomotor inhibition, cataleptogenesis, apomorphine antagonism, arousal inhibition, effect on striatal dopamine metabolism, and in vivo and in vitro anticholinergic potency. Thioridazine and the classical neuroleptics haloperidol and chlorpromazine were included in the study for comparison. The classical tests used to detect neuroleptic activity in laboratory animals were found to be poor predictors of possible clinical effectiveness of the dibenzo-epines."}
{"id": "PMID:20903", "title": "Effect of cyclophosphamide on syngeneic transplantation of adenovirus 12-transformed tumor cells in C3H/he mice.", "content": "We tested the cyclophosphamide effects against the growth of adenovirus-transformed cells and the subsequent tumor development in the syngeneic host. Cyclophosphamide did not show any effect on the tumor evolution when injected 24 and 6 hours before cell implantation. Cyclophosphamide injected 24 or 39 hours after cell implantation prevented or retarded the tumor growth. In mice bearing palpable tumors, it induced their complete regression in 85,7% of the animals, but did not effect the development of the homograft immunity.", "contents": "Effect of cyclophosphamide on syngeneic transplantation of adenovirus 12-transformed tumor cells in C3H/he mice. We tested the cyclophosphamide effects against the growth of adenovirus-transformed cells and the subsequent tumor development in the syngeneic host. Cyclophosphamide did not show any effect on the tumor evolution when injected 24 and 6 hours before cell implantation. Cyclophosphamide injected 24 or 39 hours after cell implantation prevented or retarded the tumor growth. In mice bearing palpable tumors, it induced their complete regression in 85,7% of the animals, but did not effect the development of the homograft immunity."}
{"id": "PMID:20902", "title": "[Diabetic ketoacidosis in children and adolescents. Clinical and therapeutical considerations in 25 severe cases].", "content": "Twenty-five serious cases of diabetic ketoacidosis, representing 23 patients, with ages ranging from 4 to 15 years are reported. School agers and adolescents were the groups most affected without existing significant predilection for sex. In 40% there was no success in finding the precipitating cause of the crisis; 32% was attributed to infectious processes, specially of the respiratory ducts and the rest, due to negligence in the application of insulin. The clinical signs showed: vomiting, dehydration, Kussamaul's respiration, sopor, stupor and in 5 cases a state of coma. Determinations of glucose, were integrated in 88% within the range of 451 to 750 mg % and the rest in lower figures. The pH in most was reported below 7.10 and CO2 lower than 10 mEq/l. Electrolytes in blood were generally evaluated within normal limits. Potassium in 20% was reported high, but we consider this was due to dehydration and because of its influence we recommend an electrocardiographic evaluation. Our classification which attempts to correlate the clinic and the laboratory is reported and our therapeutic scheme is discussed as well as the possible causes in two patients who died.", "contents": "[Diabetic ketoacidosis in children and adolescents. Clinical and therapeutical considerations in 25 severe cases]. Twenty-five serious cases of diabetic ketoacidosis, representing 23 patients, with ages ranging from 4 to 15 years are reported. School agers and adolescents were the groups most affected without existing significant predilection for sex. In 40% there was no success in finding the precipitating cause of the crisis; 32% was attributed to infectious processes, specially of the respiratory ducts and the rest, due to negligence in the application of insulin. The clinical signs showed: vomiting, dehydration, Kussamaul's respiration, sopor, stupor and in 5 cases a state of coma. Determinations of glucose, were integrated in 88% within the range of 451 to 750 mg % and the rest in lower figures. The pH in most was reported below 7.10 and CO2 lower than 10 mEq/l. Electrolytes in blood were generally evaluated within normal limits. Potassium in 20% was reported high, but we consider this was due to dehydration and because of its influence we recommend an electrocardiographic evaluation. Our classification which attempts to correlate the clinic and the laboratory is reported and our therapeutic scheme is discussed as well as the possible causes in two patients who died."}
{"id": "PMID:20911", "title": "Alpha-adrenergic blocking properties of droperidol on isolated blood vessels of the dog.", "content": "Concentrations of droperidol which caused a shift to the right of the dose-response curve to noradrenaline in the pulmonary artery and the saphenous vein of the dog did not affect myogenic activation by K+; they did not inhibit spontaneous activity of portal-mesenteric veins. Droperidol inhibited the contractile response to nerve stimulation, but did not affect the evoked release of 3H-noradrenaline. These experiments indicate that the vasodilator properties of smaller doses of droperidol are a result of its ability to block alpha-adrenergic receptors.", "contents": "Alpha-adrenergic blocking properties of droperidol on isolated blood vessels of the dog. Concentrations of droperidol which caused a shift to the right of the dose-response curve to noradrenaline in the pulmonary artery and the saphenous vein of the dog did not affect myogenic activation by K+; they did not inhibit spontaneous activity of portal-mesenteric veins. Droperidol inhibited the contractile response to nerve stimulation, but did not affect the evoked release of 3H-noradrenaline. These experiments indicate that the vasodilator properties of smaller doses of droperidol are a result of its ability to block alpha-adrenergic receptors."}
{"id": "PMID:20912", "title": "Respiratory effects of etomidate.", "content": "The respiratory effects of etomidate 0.3 mg/kg were studied in patients premedicated with either diazepam and atropine or papaveretum and hyoscine. The incidence of apnoea was 40% in those who received the non-narcotic premedication, compared with 27% in those who received the opiate. Those premedicated with diazepam and atropine showed a significant increase in respiratory frequency which was associated with a significant increase in minute volume 4 min after induction of anaesthesia. No such increase occurred in those premedicated with papaveretum and hyoscine. It would appear that the effects of etomidate on respiration are less than those of other i.v. induction agents, but involuntary muscle movement during induction remains a problem.", "contents": "Respiratory effects of etomidate. The respiratory effects of etomidate 0.3 mg/kg were studied in patients premedicated with either diazepam and atropine or papaveretum and hyoscine. The incidence of apnoea was 40% in those who received the non-narcotic premedication, compared with 27% in those who received the opiate. Those premedicated with diazepam and atropine showed a significant increase in respiratory frequency which was associated with a significant increase in minute volume 4 min after induction of anaesthesia. No such increase occurred in those premedicated with papaveretum and hyoscine. It would appear that the effects of etomidate on respiration are less than those of other i.v. induction agents, but involuntary muscle movement during induction remains a problem."}
{"id": "PMID:20913", "title": "Porcine malignant hyperthermia. V: Fatal hyperthermia in the Pietrain pig, associated with the infusion of alpha-adrenergic agonists.", "content": "The effects of the administration of noradrenaline alone, and noradrenaline with either phentolamine or propranolol, on thermogenesis and substrate mobilization were investigated in six Pietrain (MH-susceptible) and six Large White (unsusceptible) pigs. The infusion of noradrenaline alone produced a significantly increased lipolytic response and a significantly decreased hyperglycaemic response in Pietrain pigs compared with the Large White breed. Although noradrenaline alone produced only a small increase in body temperature in both breeds, the administration of noradrenaline with propranolol in two Pietrain pigs was associated with the development of fatal hyperthermia. In a further experiment, phenylephrine or isoprenaline was infused into six Pietrain pigs. Three pigs, receiving phenylephrine, became hyperthermic and died, whereas isoprenaline had no effect on body temperature. The results demonstrate the importance of alpha-adrenergic stimulation to heat production in MH-susceptible pigs.", "contents": "Porcine malignant hyperthermia. V: Fatal hyperthermia in the Pietrain pig, associated with the infusion of alpha-adrenergic agonists. The effects of the administration of noradrenaline alone, and noradrenaline with either phentolamine or propranolol, on thermogenesis and substrate mobilization were investigated in six Pietrain (MH-susceptible) and six Large White (unsusceptible) pigs. The infusion of noradrenaline alone produced a significantly increased lipolytic response and a significantly decreased hyperglycaemic response in Pietrain pigs compared with the Large White breed. Although noradrenaline alone produced only a small increase in body temperature in both breeds, the administration of noradrenaline with propranolol in two Pietrain pigs was associated with the development of fatal hyperthermia. In a further experiment, phenylephrine or isoprenaline was infused into six Pietrain pigs. Three pigs, receiving phenylephrine, became hyperthermic and died, whereas isoprenaline had no effect on body temperature. The results demonstrate the importance of alpha-adrenergic stimulation to heat production in MH-susceptible pigs."}
{"id": "PMID:20914", "title": "Urinary excretion and metabolism of pethidine and norpethidine in the newborn.", "content": "In seven neonates, whose mothers were given pethidine during labour, urine was collected for the first 24-40 h of life. Urinary volume and pH, and concentrations of pethidine and norpethidine in the urine were measured. Urine flow rate was low for the first 7-22 h, and then high for about 12 h. The rate of excretion of pethidine and norepethidine was approximately parallel to the urine flow rate. However, the ratio of the rate of excretion of norpethidine to that of pethidine increased with time and the concentration of norpethidine in urine decreased first and then, after 18 h, increased significantly. These findings that the neonate can metabolize pethidine, although the rate of metabolism is probably less than in the adult. The total amounts of pethidine and norpethidine excreted in the first 24 h after birth were positively related to the dose-delivery interval in the mother for intervals up to at least 5 h. From the data it is estimated that 95% of the total pethidine transferred from the mother would be eliminated by the baby by the 2nd to 3rd day after birth.", "contents": "Urinary excretion and metabolism of pethidine and norpethidine in the newborn. In seven neonates, whose mothers were given pethidine during labour, urine was collected for the first 24-40 h of life. Urinary volume and pH, and concentrations of pethidine and norpethidine in the urine were measured. Urine flow rate was low for the first 7-22 h, and then high for about 12 h. The rate of excretion of pethidine and norepethidine was approximately parallel to the urine flow rate. However, the ratio of the rate of excretion of norpethidine to that of pethidine increased with time and the concentration of norpethidine in urine decreased first and then, after 18 h, increased significantly. These findings that the neonate can metabolize pethidine, although the rate of metabolism is probably less than in the adult. The total amounts of pethidine and norpethidine excreted in the first 24 h after birth were positively related to the dose-delivery interval in the mother for intervals up to at least 5 h. From the data it is estimated that 95% of the total pethidine transferred from the mother would be eliminated by the baby by the 2nd to 3rd day after birth."}
{"id": "PMID:20915", "title": "A spectrofluorometric method for the determination of ajmaline in plasma.", "content": "1 Ajmaline was found to have maximum fluorescence at neutral pH with 300 nm excitation and 365 nm emission wavelengths (corrected). 2 The fluorescence intensity had a linear relationship to concentration up to 50 microgram ml-1 and the recovery of ajmaline after extraction from plasma was 92.5 +/- 3%. 3 Extraction of drug-free plasma and of samples containing known concentrations of ajmaline showed that drug levels in the range found clinically could be measured accurately by fluorimetry. 4 Serial plasma ajmaline concentrations were measured in a subject after intravenous injection of ajmaline (50 mg). The rates of plasma clearance of the drug were found to be similar to those obtained in previous studies.", "contents": "A spectrofluorometric method for the determination of ajmaline in plasma. 1 Ajmaline was found to have maximum fluorescence at neutral pH with 300 nm excitation and 365 nm emission wavelengths (corrected). 2 The fluorescence intensity had a linear relationship to concentration up to 50 microgram ml-1 and the recovery of ajmaline after extraction from plasma was 92.5 +/- 3%. 3 Extraction of drug-free plasma and of samples containing known concentrations of ajmaline showed that drug levels in the range found clinically could be measured accurately by fluorimetry. 4 Serial plasma ajmaline concentrations were measured in a subject after intravenous injection of ajmaline (50 mg). The rates of plasma clearance of the drug were found to be similar to those obtained in previous studies."}
{"id": "PMID:20916", "title": "A sensitive radioenzymatic assay for adrenaline and noradrenaline in plasma.", "content": "1 An existing radioenzymatic assay for plasma catecholamines using catechol-o-methyl transferase and [3H]-S-adenosyl-methionine has been modified resulting in a more sensitive assay for the measurement of plasma adrenaline and noradrenaline. 2 The lower limit of sensitivity for this method is 25 pg for adrenaline and 30 pg for noradrenaline/ml of plasma. 3 Resting supine (60 min) plasma adrenaline concentration was (mean +/- s.d.) 124 +/- 76 pg/ml(n=11) in males and 130 +/- 71 pg/ml (n=7) in females; plasma noradrenaline concentrations were respectively 444 +/- 129 pg/ml and 550 +/- 87 pg/ml. 4 The changes in plasma catecholamine concentrations in response to 40 degrees head-up tilt have been determined in a group of healthy normal subjects and have been shown to be related to changes in blood pressure and heart rate.", "contents": "A sensitive radioenzymatic assay for adrenaline and noradrenaline in plasma. 1 An existing radioenzymatic assay for plasma catecholamines using catechol-o-methyl transferase and [3H]-S-adenosyl-methionine has been modified resulting in a more sensitive assay for the measurement of plasma adrenaline and noradrenaline. 2 The lower limit of sensitivity for this method is 25 pg for adrenaline and 30 pg for noradrenaline/ml of plasma. 3 Resting supine (60 min) plasma adrenaline concentration was (mean +/- s.d.) 124 +/- 76 pg/ml(n=11) in males and 130 +/- 71 pg/ml (n=7) in females; plasma noradrenaline concentrations were respectively 444 +/- 129 pg/ml and 550 +/- 87 pg/ml. 4 The changes in plasma catecholamine concentrations in response to 40 degrees head-up tilt have been determined in a group of healthy normal subjects and have been shown to be related to changes in blood pressure and heart rate."}
{"id": "PMID:20917", "title": "Effect of the 1,5-benzodiazepines, clobazam and triflubazam, on sleep in man.", "content": "1 The effect of the 1,5-benzodiazepines, clobazam (10 and 20 mg) and triflubazam (20 and 40 mg), on sleep was studied in six healthy males using electroencephalography for sleep measures and analogue scales for subjective assessments of well being and sleep quality. The effect of clobazam was limited to the night of ingestion. There was some evidence from subjective assessments that the effect of triflubazam may have persisted beyond the night of ingestion. 2 No effect of clobazam or triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep. With clobazam sleep onset latency was shortened (P less than 0.05), but this effect was not seen with triflubazam. The latency to stage 3 was shortened by both drugs. There was evidence of reduced duration of awake (stage 0) activity and drowsy (stage 1) sleep with both drugs. 3 The percentage stage 1 sleep was reduced by clobazam (10 and 20 mg) and by triflubazam (20 mg) (P less than 0.05), though the effect was not significant with triflubazam (40 mg). Clobazam (20 mg) increased the percentage stage 2 sleep (P less than 0.05), but reduced the percentage stage 3 (P less than 0.01) and stages 3 + 4 (P less than 0.05) sleep. There were no other effects on percentage of total sleep time occupied by various sleep stages or in duration (min) of sleep stages, except that the duration (min) of sleep stages, except that the duration (min) of stage 2 sleep in the second 2 h interval of sleep was increased with clobazam (20 mg) (P less than 0.01). 4 Subjects reported impaired sleep with triflubazam (40 mg) (P less than 0.05), and a sense of less wakefulness the morning after ingestion of clobazam (10 and 20 mg) (P less than 0.01) and triflubazam (40 mg) (P less than 0.05).", "contents": "Effect of the 1,5-benzodiazepines, clobazam and triflubazam, on sleep in man. 1 The effect of the 1,5-benzodiazepines, clobazam (10 and 20 mg) and triflubazam (20 and 40 mg), on sleep was studied in six healthy males using electroencephalography for sleep measures and analogue scales for subjective assessments of well being and sleep quality. The effect of clobazam was limited to the night of ingestion. There was some evidence from subjective assessments that the effect of triflubazam may have persisted beyond the night of ingestion. 2 No effect of clobazam or triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep. With clobazam sleep onset latency was shortened (P less than 0.05), but this effect was not seen with triflubazam. The latency to stage 3 was shortened by both drugs. There was evidence of reduced duration of awake (stage 0) activity and drowsy (stage 1) sleep with both drugs. 3 The percentage stage 1 sleep was reduced by clobazam (10 and 20 mg) and by triflubazam (20 mg) (P less than 0.05), though the effect was not significant with triflubazam (40 mg). Clobazam (20 mg) increased the percentage stage 2 sleep (P less than 0.05), but reduced the percentage stage 3 (P less than 0.01) and stages 3 + 4 (P less than 0.05) sleep. There were no other effects on percentage of total sleep time occupied by various sleep stages or in duration (min) of sleep stages, except that the duration (min) of sleep stages, except that the duration (min) of stage 2 sleep in the second 2 h interval of sleep was increased with clobazam (20 mg) (P less than 0.01). 4 Subjects reported impaired sleep with triflubazam (40 mg) (P less than 0.05), and a sense of less wakefulness the morning after ingestion of clobazam (10 and 20 mg) (P less than 0.01) and triflubazam (40 mg) (P less than 0.05)."}
{"id": "PMID:20918", "title": "Clobazam, a 1,5-benzodiazepine, and car-driving ability.", "content": "1 The effects of clobazam, a new anxiolytic agent (a 1,5-benzodiazepine) on car-driving ability and other tests of psychomotor performance were investigated in a double-blind, cross-over study v. placebo in normal volunteers. 2 Clobazam (20 mg) or placebo was given nightly for six nights to ten volunteers and subjective ratings of sleep and subjective and objective assessments of behaviour and psychomotor performance on the morning following drug ingestion were recorded. 3 Clobazam significantly improved the subjective ratings of sleep induction and quality of induced sleep. 4 Clobazam did not significantly impair performance in a variety of psychomotor tests and car-driving ability. 5 The validity of the measures used and the relevance of the findings to real life car-driving situations are discussed.", "contents": "Clobazam, a 1,5-benzodiazepine, and car-driving ability. 1 The effects of clobazam, a new anxiolytic agent (a 1,5-benzodiazepine) on car-driving ability and other tests of psychomotor performance were investigated in a double-blind, cross-over study v. placebo in normal volunteers. 2 Clobazam (20 mg) or placebo was given nightly for six nights to ten volunteers and subjective ratings of sleep and subjective and objective assessments of behaviour and psychomotor performance on the morning following drug ingestion were recorded. 3 Clobazam significantly improved the subjective ratings of sleep induction and quality of induced sleep. 4 Clobazam did not significantly impair performance in a variety of psychomotor tests and car-driving ability. 5 The validity of the measures used and the relevance of the findings to real life car-driving situations are discussed."}
{"id": "PMID:20919", "title": "Further studies of rimiterol and salbutamol administered by intermittent positive-pressure ventilation, and an important observation on the technique of using the Bennett ventilator.", "content": "1. Using the same technique of administering drugs by intermittent positive-pressure ventilation as used in previous studies a source of contamination of solutions nebulized was discovered. This was rectified by using a new ventilator and completely separate patient circuits for each solution nebulized. 2 Salbutamol 0.5% and 0.25% solutions achieved the same degree of bronchodilatation, but there was a significantly greater increase in heart rate produced by salbutamol 0.5%. 3 Rimiterol 0.5% and salbutamol 0.25% produced similar peak mean improvements in FEV and also induced the same degree of tachycardia, but the duration of these effects were significantly shorter in the case of rimiterol. 4 The sustained degree of bronchodilatation achieved by salbutamol 0.25% could not be mirrored by giving two doses of rimiterol 0.5%, the second dose 2 h after the first. 5 Rimiterol 0.5% induced a degree of tachycardia which was similar in peak effect to that observed after salbutamol 0.25%. However, in the controls the second dose of rimiterol, given 2 h after the first, was responsible for only a small increase in heart rate which was not significantly different than that after saline in the other three treatment groups.", "contents": "Further studies of rimiterol and salbutamol administered by intermittent positive-pressure ventilation, and an important observation on the technique of using the Bennett ventilator. 1. Using the same technique of administering drugs by intermittent positive-pressure ventilation as used in previous studies a source of contamination of solutions nebulized was discovered. This was rectified by using a new ventilator and completely separate patient circuits for each solution nebulized. 2 Salbutamol 0.5% and 0.25% solutions achieved the same degree of bronchodilatation, but there was a significantly greater increase in heart rate produced by salbutamol 0.5%. 3 Rimiterol 0.5% and salbutamol 0.25% produced similar peak mean improvements in FEV and also induced the same degree of tachycardia, but the duration of these effects were significantly shorter in the case of rimiterol. 4 The sustained degree of bronchodilatation achieved by salbutamol 0.25% could not be mirrored by giving two doses of rimiterol 0.5%, the second dose 2 h after the first. 5 Rimiterol 0.5% induced a degree of tachycardia which was similar in peak effect to that observed after salbutamol 0.25%. However, in the controls the second dose of rimiterol, given 2 h after the first, was responsible for only a small increase in heart rate which was not significantly different than that after saline in the other three treatment groups."}
{"id": "PMID:20922", "title": "The excretion of gamma-glutamyl transferase in pregnancy.", "content": "A cross-sectional study of gamma-glutamyl transferase (gamma-GT) excretion in 316 healthy pregnant women showed the enzyme excretion (mU per mmol creatinine) was significantly higher than that of a non-pregnant control group. The increase was apparent before the end of the first trimester and continued therafter. These changes may be indicative of hypertrophy and/or hyperplasia of the nephron and be part of the overall renal adaptation to normal pregnancy. Even higher levels were recorded in three obstetric patients in whom renal complications were to be expected and this may indicate a specific type of renal damage.", "contents": "The excretion of gamma-glutamyl transferase in pregnancy. A cross-sectional study of gamma-glutamyl transferase (gamma-GT) excretion in 316 healthy pregnant women showed the enzyme excretion (mU per mmol creatinine) was significantly higher than that of a non-pregnant control group. The increase was apparent before the end of the first trimester and continued therafter. These changes may be indicative of hypertrophy and/or hyperplasia of the nephron and be part of the overall renal adaptation to normal pregnancy. Even higher levels were recorded in three obstetric patients in whom renal complications were to be expected and this may indicate a specific type of renal damage."}
{"id": "PMID:20927", "title": "Calcium-induced cooperativity of manganese binding to concanavalin A.", "content": "Titrations employing electron spin resonance spectroscopy and equilibrium dialysis studies have revealed that Mn2+ binding to concanavalin A is cooperative in the presence and noncooperative in the absence of Ca2+. The degree of cooperativity increases with increasing pH. Hill coefficients range from 1.4 at pH 5.0 to 1.8 at pH 6.85. In addition to inducing cooperativity in Mn2+ binding, Ca2+ influences the pH dependence and increases the affinity of Mn2+ binding. In contrast to previous suggestions based mostly on work conducted near pH 5, demetallized concanavalin A does bind Ca2+ with an appreciable binding constant. These observations indicate that at physiological pH the role of metal ions in determining functional properties of concanavalin A is different from that suggested by metal binding studies conducted at lower pH values.", "contents": "Calcium-induced cooperativity of manganese binding to concanavalin A. Titrations employing electron spin resonance spectroscopy and equilibrium dialysis studies have revealed that Mn2+ binding to concanavalin A is cooperative in the presence and noncooperative in the absence of Ca2+. The degree of cooperativity increases with increasing pH. Hill coefficients range from 1.4 at pH 5.0 to 1.8 at pH 6.85. In addition to inducing cooperativity in Mn2+ binding, Ca2+ influences the pH dependence and increases the affinity of Mn2+ binding. In contrast to previous suggestions based mostly on work conducted near pH 5, demetallized concanavalin A does bind Ca2+ with an appreciable binding constant. These observations indicate that at physiological pH the role of metal ions in determining functional properties of concanavalin A is different from that suggested by metal binding studies conducted at lower pH values."}
{"id": "PMID:20929", "title": "Spontaneous, reversible protein cross-linking in the human erythrocyte membrane. Temperature and pH dependence.", "content": "Changes in pH significantly affect the morphology and physical properties of red cell membranes. We have explored the molecular basis for these phenomena by characterizing the pattern of protein disulfide cross-linkages formed spontaneously in ghost exposed to acid pH or elevated temperature (37 degrees C). Protein aggregation was analyzed by two-dimensional polyacrylamide gel electrophoresis in sodium dodecyl sulfate. incubation of ghosts at pH 4.0 to 5.5 (0-4 degrees C) yielded (i) complexes of spectrin and band 3, (ii) complexes of actin and band 3, (iii) band 3 complexes, i.e. dimer and trimer, and (iv) heterogeneous aggregates involving spectrin, band 3, band 4.2, and actin in varying proportions. Aggregation was maximal near the isoelectric points of the major membrane proteins, and appeared to reflect (i) the aggregation of intramembrane particles including band 3 and (ii) more intimate contact between spectrin-actin meshwork and band 3.", "contents": "Spontaneous, reversible protein cross-linking in the human erythrocyte membrane. Temperature and pH dependence. Changes in pH significantly affect the morphology and physical properties of red cell membranes. We have explored the molecular basis for these phenomena by characterizing the pattern of protein disulfide cross-linkages formed spontaneously in ghost exposed to acid pH or elevated temperature (37 degrees C). Protein aggregation was analyzed by two-dimensional polyacrylamide gel electrophoresis in sodium dodecyl sulfate. incubation of ghosts at pH 4.0 to 5.5 (0-4 degrees C) yielded (i) complexes of spectrin and band 3, (ii) complexes of actin and band 3, (iii) band 3 complexes, i.e. dimer and trimer, and (iv) heterogeneous aggregates involving spectrin, band 3, band 4.2, and actin in varying proportions. Aggregation was maximal near the isoelectric points of the major membrane proteins, and appeared to reflect (i) the aggregation of intramembrane particles including band 3 and (ii) more intimate contact between spectrin-actin meshwork and band 3."}
{"id": "PMID:20930", "title": "Kinetics of binding of oligosaccharides to a homogeneous pneumococcal antibody: dependence on antigen chain length suggests a labile intermediate complex.", "content": "Temperature-jump experiments were performed with di-, tetra-, and hexasaccharides derived from type III pneumococcal polysaccharide using a homogeneous corresponding antibody IgG 45-394. A decrease in stability of the oligosaccharide-antibody complexes with decreasing chain length was observed and entirely reflected in the decrease of the association rate constants which were 1.7 X 10(4) M-1 s-1 for the di-, 3.7 X 10(5) M-1 s-1 for the tetra-, and 1.1 X 10(6) M-1 s-1 for the hexasaccharide at 23 degrees C. The dissociation rate constants for all oligomers were about 12 s-1. This marked chain-length dependence of the association rate constants as well as their low values are unexpected for a single binding step. A mechanism is proposed which consists of a fast formation of a labile oligosaccharide-antibody precomplex followed by a slow isomerization step which is induced by the oligosaccharide ligands but which is chain-length independent.", "contents": "Kinetics of binding of oligosaccharides to a homogeneous pneumococcal antibody: dependence on antigen chain length suggests a labile intermediate complex. Temperature-jump experiments were performed with di-, tetra-, and hexasaccharides derived from type III pneumococcal polysaccharide using a homogeneous corresponding antibody IgG 45-394. A decrease in stability of the oligosaccharide-antibody complexes with decreasing chain length was observed and entirely reflected in the decrease of the association rate constants which were 1.7 X 10(4) M-1 s-1 for the di-, 3.7 X 10(5) M-1 s-1 for the tetra-, and 1.1 X 10(6) M-1 s-1 for the hexasaccharide at 23 degrees C. The dissociation rate constants for all oligomers were about 12 s-1. This marked chain-length dependence of the association rate constants as well as their low values are unexpected for a single binding step. A mechanism is proposed which consists of a fast formation of a labile oligosaccharide-antibody precomplex followed by a slow isomerization step which is induced by the oligosaccharide ligands but which is chain-length independent."}
{"id": "PMID:20932", "title": "Interaction of zinc and hemoglobin: binding of zinc and the oxygen affinity.", "content": "Stripped human hemoglobin was shown to have a high apparent zinc association constant of 1.3 X 10(7) M-1 with a stoichiometry of one zinc for every two hemes. The saturation of this site produces a dramatic 3.7-fold increase in the oxygen affinity. The effect of zinc on the oxygen affinity is interrelated with the interaction of 2,3-diphosphoglyceric acid (2,3-DPG) and hemoglobin. Thus, a smaller zinc effect is observed in the presence of added 2,3-DPG. Information about the location of the zinc-binding site responsible for the increased oxygen affinity has been obtained by comparing the binding of zinc to various hemoglobins. Blocking the beta93 sulfhydryl group decreases the apparent zinc association constant by an order of magnitude. The substitution of histidine-beta143 in hemoglobin Abruzzo [beta143 (H21) His leads to Arg] and hemoglobin Little Rock [beta143 (H21) His leads to Gln] decreases the apparent zinc association constant by two orders of magnitude. The substitution of histidine-beta143 by other amino acids and the reaction of the beta93 sulfhydryl group are known to produce dramatic increases in the oxygen affinity. The binding of zinc to one or both of these amino acids can, therefore, explain the zinc-induced increase in the oxygen affinity.", "contents": "Interaction of zinc and hemoglobin: binding of zinc and the oxygen affinity. Stripped human hemoglobin was shown to have a high apparent zinc association constant of 1.3 X 10(7) M-1 with a stoichiometry of one zinc for every two hemes. The saturation of this site produces a dramatic 3.7-fold increase in the oxygen affinity. The effect of zinc on the oxygen affinity is interrelated with the interaction of 2,3-diphosphoglyceric acid (2,3-DPG) and hemoglobin. Thus, a smaller zinc effect is observed in the presence of added 2,3-DPG. Information about the location of the zinc-binding site responsible for the increased oxygen affinity has been obtained by comparing the binding of zinc to various hemoglobins. Blocking the beta93 sulfhydryl group decreases the apparent zinc association constant by an order of magnitude. The substitution of histidine-beta143 in hemoglobin Abruzzo [beta143 (H21) His leads to Arg] and hemoglobin Little Rock [beta143 (H21) His leads to Gln] decreases the apparent zinc association constant by two orders of magnitude. The substitution of histidine-beta143 by other amino acids and the reaction of the beta93 sulfhydryl group are known to produce dramatic increases in the oxygen affinity. The binding of zinc to one or both of these amino acids can, therefore, explain the zinc-induced increase in the oxygen affinity."}
{"id": "PMID:20934", "title": "Spectrophotometric titration of a single carboxyl group at the active site of ribonuclease T1.", "content": "Low-pH-induced difference spectra for ribonuclease T1, which were determined using a reference solution at pH 6, consisted of a shorter wavelength component from 270 to 285 nm that relfected an ionization having a pKa of 3.54 and a longer wavelength component above 285 nm that reflected an ionization having a pKa of 4.29. The temperature dependence of the pKa value for data at 300 nm is consistent with its representing the dissociation of a carboxyl group. In addition, the pKa determined at this wavelength significantly decreased at lower ionic strength. Similar experiments which were conducted using catalytically inactive gamma-carboxymethyl-Glu-58-ribonuclease T1 gave difference spectra having only the shorter wavelength component and were characterized by a single pKa of 3.53. It is concluded that the longer wavelength component of the difference spectra is due to the ionization of Glu-58. The pKa determined for this residue in the present study agrees with one found previously from kinetic studies which supports a role for Glu-58 in catalysis. Furthermore, the results suggest a model for the interaction of Glu-58 with histidine and tryptophan residues at the active site.", "contents": "Spectrophotometric titration of a single carboxyl group at the active site of ribonuclease T1. Low-pH-induced difference spectra for ribonuclease T1, which were determined using a reference solution at pH 6, consisted of a shorter wavelength component from 270 to 285 nm that relfected an ionization having a pKa of 3.54 and a longer wavelength component above 285 nm that reflected an ionization having a pKa of 4.29. The temperature dependence of the pKa value for data at 300 nm is consistent with its representing the dissociation of a carboxyl group. In addition, the pKa determined at this wavelength significantly decreased at lower ionic strength. Similar experiments which were conducted using catalytically inactive gamma-carboxymethyl-Glu-58-ribonuclease T1 gave difference spectra having only the shorter wavelength component and were characterized by a single pKa of 3.53. It is concluded that the longer wavelength component of the difference spectra is due to the ionization of Glu-58. The pKa determined for this residue in the present study agrees with one found previously from kinetic studies which supports a role for Glu-58 in catalysis. Furthermore, the results suggest a model for the interaction of Glu-58 with histidine and tryptophan residues at the active site."}
{"id": "PMID:20935", "title": "Selective phosphorylation of erythrocyte membrane proteins by the solubilized membrane protein kinases.", "content": "This report describes the substrate and phosphoryl donor specificities of solubilized erythrocyte membrane cyclic adenosine 3',5'-monophosphate (cAMP)-independent protein kinases toward human and rabbit erythrocyte membrane proteins. Three types of substrate preparations have been utilized: heat-inactivated ghosts, isolated spectrin, and 2,3-dimethylmaleic anhydride (DMMA)-extracted membranes. A 30 000-dalton protein kinase, extracted from either human or rabbit erythrocyte membranes, catalyzes the phosphorylation of heat-inactivated membranes in the presence of ATP. The resulting phosphorylation profile is analogous to that of the autophosphorylation of membranes with ATP (in the absence of cAMP). These kinases also phosphorylate band 2 of isolated spectrin and band 3, but not glycophorin, in the DMMA-extracted ghosts. The ability of the 30 000-dalton kinases to use GTP as a phosphoryl donor appears to be related to the substrate or some other membrane factor. A second kinase, which is 100 000 daltons and derived from rabbit erythrocyte membranes, uses ATP or GTP to phosphorylate membrane proteins 2, 2.1, 2.9-3 in heat-inactivated ghosts, band 2 in isolated spectrin, glycophorin, and to a lesser extent, band 3 in the DMMA-extracted ghosts.", "contents": "Selective phosphorylation of erythrocyte membrane proteins by the solubilized membrane protein kinases. This report describes the substrate and phosphoryl donor specificities of solubilized erythrocyte membrane cyclic adenosine 3',5'-monophosphate (cAMP)-independent protein kinases toward human and rabbit erythrocyte membrane proteins. Three types of substrate preparations have been utilized: heat-inactivated ghosts, isolated spectrin, and 2,3-dimethylmaleic anhydride (DMMA)-extracted membranes. A 30 000-dalton protein kinase, extracted from either human or rabbit erythrocyte membranes, catalyzes the phosphorylation of heat-inactivated membranes in the presence of ATP. The resulting phosphorylation profile is analogous to that of the autophosphorylation of membranes with ATP (in the absence of cAMP). These kinases also phosphorylate band 2 of isolated spectrin and band 3, but not glycophorin, in the DMMA-extracted ghosts. The ability of the 30 000-dalton kinases to use GTP as a phosphoryl donor appears to be related to the substrate or some other membrane factor. A second kinase, which is 100 000 daltons and derived from rabbit erythrocyte membranes, uses ATP or GTP to phosphorylate membrane proteins 2, 2.1, 2.9-3 in heat-inactivated ghosts, band 2 in isolated spectrin, glycophorin, and to a lesser extent, band 3 in the DMMA-extracted ghosts."}
{"id": "PMID:20940", "title": "Effect of H+ on the K+ activation of adenosine-5'-monophosphate aminohydrolase.", "content": "The activation of adenosine-5'-monophosphate aminohydrolase from rabbit skeletal muscle by H+ has been demonstrated. Evidence is presented which indicates that the binding of H+ and K+ is linked, in that the dissociation constant (KA) for K+ activation is reduced as the pH is lowered. Concomitantly, the pK of several enzyme functional groups is changed when K+ is added to a solution of enzyme. This change is pK results in an uptake or release of H+, depending on the pH, and shows that K+ interacts with the enzyme to achieve its effect. The uptake or release of H+ provides a simple method of following conformational changes in the enzyme following interaction of K+. The KD for K+ interaction monitored by following pH changes is the same within experimental error as that measured from kinetic data.", "contents": "Effect of H+ on the K+ activation of adenosine-5'-monophosphate aminohydrolase. The activation of adenosine-5'-monophosphate aminohydrolase from rabbit skeletal muscle by H+ has been demonstrated. Evidence is presented which indicates that the binding of H+ and K+ is linked, in that the dissociation constant (KA) for K+ activation is reduced as the pH is lowered. Concomitantly, the pK of several enzyme functional groups is changed when K+ is added to a solution of enzyme. This change is pK results in an uptake or release of H+, depending on the pH, and shows that K+ interacts with the enzyme to achieve its effect. The uptake or release of H+ provides a simple method of following conformational changes in the enzyme following interaction of K+. The KD for K+ interaction monitored by following pH changes is the same within experimental error as that measured from kinetic data."}
{"id": "PMID:20941", "title": "Phosphorylation of nuclear proteins in rat regenerating liver.", "content": "In studies of the phosphorylated proteins in rat liver and Walker-256, it was established that the ratio of various fractions of P-N linkages to P-O linkages varies from 0.6 to 3.1. In rat regenerating liver nuclei, the ratio of P-N and P-O varies with time after partial hepatectomy. Using [3H]-lysine and 32Pi, it is shown that phosphoryllysine forms in some new and, presumably, some preexisting H1 molecules. Using [3H]histidine and 32Pi, it is shown that phosphohistidine forms exclusively in preexisting H4. The half-life of H4 phosphohistidine appears to be about 2 h.", "contents": "Phosphorylation of nuclear proteins in rat regenerating liver. In studies of the phosphorylated proteins in rat liver and Walker-256, it was established that the ratio of various fractions of P-N linkages to P-O linkages varies from 0.6 to 3.1. In rat regenerating liver nuclei, the ratio of P-N and P-O varies with time after partial hepatectomy. Using [3H]-lysine and 32Pi, it is shown that phosphoryllysine forms in some new and, presumably, some preexisting H1 molecules. Using [3H]histidine and 32Pi, it is shown that phosphohistidine forms exclusively in preexisting H4. The half-life of H4 phosphohistidine appears to be about 2 h."}
{"id": "PMID:20943", "title": "Effect of pressure upon the fluorescence of various flavodoxins.", "content": "The effects of hydrostatic pressure in the range of 10(-3) to 11 kbar on the fluorescence of flavodoxins from Peptostreptococcus elsdenii, Desulfovibrio vulgaris, Azotobacter vinelandii, and Clostridium MP were investigated. The first three flavoproteins showed under high pressure enhancements of flavin fluorescence of over 50 times resulting from the release of flavin mononucleotide from the protein complex. The Clostridial flavodoxin showed a very much smaller fluorescence change. At pH 7.5 the high-pressure fluorescence changes of the flavodoxins of D. vulgaris and P. elsdenii were not reversed by decompression, but in A. Vinelandii the pressure changes were over 80% reversible. At pH 5 over 80% reversibility was restored to the flavodoxins of D. vulgaris and P. elsdenii, although the pressure dependence of the fluorescence changes was very similar in the reversible and irreversible cases. The midpoint pressures in the reversible reactions were 4.7 kbar (D. vulgaris), 8.7 kbar (P. elsdenii), and 10.6 kbar (A. vinelandii) indicating specific differences in the flavin binding regions. Apparent volume changes in these reactions were 65-75 mL/mol indicating participation of a large fraction of the protein in the pressure-induced changes. The irreversible changes are not related to protein aggregation and are believed to result from a pressure-dependent covalent modification, not yet characterized, of the flavin binding region of the protein.", "contents": "Effect of pressure upon the fluorescence of various flavodoxins. The effects of hydrostatic pressure in the range of 10(-3) to 11 kbar on the fluorescence of flavodoxins from Peptostreptococcus elsdenii, Desulfovibrio vulgaris, Azotobacter vinelandii, and Clostridium MP were investigated. The first three flavoproteins showed under high pressure enhancements of flavin fluorescence of over 50 times resulting from the release of flavin mononucleotide from the protein complex. The Clostridial flavodoxin showed a very much smaller fluorescence change. At pH 7.5 the high-pressure fluorescence changes of the flavodoxins of D. vulgaris and P. elsdenii were not reversed by decompression, but in A. Vinelandii the pressure changes were over 80% reversible. At pH 5 over 80% reversibility was restored to the flavodoxins of D. vulgaris and P. elsdenii, although the pressure dependence of the fluorescence changes was very similar in the reversible and irreversible cases. The midpoint pressures in the reversible reactions were 4.7 kbar (D. vulgaris), 8.7 kbar (P. elsdenii), and 10.6 kbar (A. vinelandii) indicating specific differences in the flavin binding regions. Apparent volume changes in these reactions were 65-75 mL/mol indicating participation of a large fraction of the protein in the pressure-induced changes. The irreversible changes are not related to protein aggregation and are believed to result from a pressure-dependent covalent modification, not yet characterized, of the flavin binding region of the protein."}
{"id": "PMID:20944", "title": "Occurrence of fatty acid chlorohydrins in jellyfish lipids.", "content": "Fatty acid chlorohydrins are characterized as lipid components of an edible jellyfish. The four isomers 9-chloro-10-hydroxypalmitic acid, 10-chloro-9-hydroxypalmitic acid, 9-chloro-10-hydroxystearic acid, and 10-chloro-9-hydroxystearic acid were identified by gas chromatography-mass spectrometry comparison of the methyl esters and their trimethylsilyl derivatives with known synthetic samples. Two additional isomers, 11-chloro-12-hydroxystearic acid and 12-chloro-11-hydroxystearic acid, were also found in the lipid by the identification of the expected mass spectral fragments of the trimethylsilyl (Me3Si) derivative of their methyl esters. These six isomeric compounds represented approximately 1.4% of the total extractable jellyfish lipid and were released from the lipid as methyl esters by boron trifluoride-methanol treatment. These isomers account for only about 30% of the organic chlorine in the lipid. Evidence is given that the remaining organic chlorine is also present as fatty acid chlorohydrins containing more than one hydroxyl group.", "contents": "Occurrence of fatty acid chlorohydrins in jellyfish lipids. Fatty acid chlorohydrins are characterized as lipid components of an edible jellyfish. The four isomers 9-chloro-10-hydroxypalmitic acid, 10-chloro-9-hydroxypalmitic acid, 9-chloro-10-hydroxystearic acid, and 10-chloro-9-hydroxystearic acid were identified by gas chromatography-mass spectrometry comparison of the methyl esters and their trimethylsilyl derivatives with known synthetic samples. Two additional isomers, 11-chloro-12-hydroxystearic acid and 12-chloro-11-hydroxystearic acid, were also found in the lipid by the identification of the expected mass spectral fragments of the trimethylsilyl (Me3Si) derivative of their methyl esters. These six isomeric compounds represented approximately 1.4% of the total extractable jellyfish lipid and were released from the lipid as methyl esters by boron trifluoride-methanol treatment. These isomers account for only about 30% of the organic chlorine in the lipid. Evidence is given that the remaining organic chlorine is also present as fatty acid chlorohydrins containing more than one hydroxyl group."}
{"id": "PMID:20946", "title": "Steady-state kinetics of electron transfer through cytochrome chain of uncoupled submitochondrial particles. I. General kinetic analysis.", "content": "Steady-state kinetics of electron transfer through the cytochrome chain of uncoupled ultrasonic submitochondrial particles at different pH values has been studied. Rate constants calculated from the Pring equation (ki' = V/PirPi+1ox) increased with the increase of the rate of the process. As in the previous work (Saks, V. A., Kupriyanov, V. V. and Luzikov, V. N. (1972) Biochim. Biophys. Acta 283, 42-53) this dependence was linear, but only at comparatively low rates of electron transfer. To explain the experimental data several kinetic models, based on the assumption that respiratory chains are activated when functioning, have been proposed and analysed. The best agreement with the experimental data was obtained for the model suggesting that the rate of activation of the carriers is directly proportional to the overall rate of electron transfer and to the proportion of non-activated respiratory chains in the system. Hence it appeared that electron transfer through already activated chains entailed activation of adjacent non-activated chains. This model allowed rate constants for non-activated (ki) and activated (ki) states of the carriers, as well as the life-time of the activated carriers (tau) to be determined.", "contents": "Steady-state kinetics of electron transfer through cytochrome chain of uncoupled submitochondrial particles. I. General kinetic analysis. Steady-state kinetics of electron transfer through the cytochrome chain of uncoupled ultrasonic submitochondrial particles at different pH values has been studied. Rate constants calculated from the Pring equation (ki' = V/PirPi+1ox) increased with the increase of the rate of the process. As in the previous work (Saks, V. A., Kupriyanov, V. V. and Luzikov, V. N. (1972) Biochim. Biophys. Acta 283, 42-53) this dependence was linear, but only at comparatively low rates of electron transfer. To explain the experimental data several kinetic models, based on the assumption that respiratory chains are activated when functioning, have been proposed and analysed. The best agreement with the experimental data was obtained for the model suggesting that the rate of activation of the carriers is directly proportional to the overall rate of electron transfer and to the proportion of non-activated respiratory chains in the system. Hence it appeared that electron transfer through already activated chains entailed activation of adjacent non-activated chains. This model allowed rate constants for non-activated (ki) and activated (ki) states of the carriers, as well as the life-time of the activated carriers (tau) to be determined."}
{"id": "PMID:20947", "title": "Conformation-dependent participation of the protein in electron equivalent transfer to cytochrome c.", "content": "When ferricytochrome c is reduced by H atoms (produced by pulse radiolysis) at neutral pH where it is in a closed protein configuration, a considerable percentage of the reduction proceeds through electron equivalent transfer via the protein. At pH 2.0, where cytochrome c is in an open configuration, H atoms reduce by adding directly to the heme porphyrin. The intermediate then observed is identified through similarity with that formed on ferriheme alone.", "contents": "Conformation-dependent participation of the protein in electron equivalent transfer to cytochrome c. When ferricytochrome c is reduced by H atoms (produced by pulse radiolysis) at neutral pH where it is in a closed protein configuration, a considerable percentage of the reduction proceeds through electron equivalent transfer via the protein. At pH 2.0, where cytochrome c is in an open configuration, H atoms reduce by adding directly to the heme porphyrin. The intermediate then observed is identified through similarity with that formed on ferriheme alone."}
{"id": "PMID:20948", "title": "Site of bicarbonate effect in Hill reaction. Evidence from the use of artificial electron acceptors and donors.", "content": "Using artificial electron donors and acceptors, it is shown here that the major HCO3- effect in the Hill reaction is after the \"primary\" electron acceptor (Q) of Photosystem II and before the site of action of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (at the plastoquinone pool). Chloroplasts in the presence of both 3-(3',4'-dichlorophenyl)-1,1-dimethylurea, which blocks electron flow from the reduced primary acdeptor Q- to the plastoquinone pool, and silicomolybdate, which accepts electrons from Q-, show no significant bicarbonate stimulation of electron flow. However, a 6-7 fold stimulation is clearly observed when oxidized diaminodurene, as an electron acceptor, and dibromothymoquinone, as an inhibitor of electron flow beyond the plastoquinone pool, are used. In the same chloroplast preparation no measurable effect of bicarbonate is observed in a Photosystem I reaction as monitored by electron flow from reduced diaminodurene to methyl viologen in the presence of 3- (3',4'-dichlorophenyl)-1,1-dimethylurea. The insensitivity of the bicarbonate effect to uncouplers of photophosphorylation and the dependence of this effect on the presence of a weak acid anion and on external pH are also reported.", "contents": "Site of bicarbonate effect in Hill reaction. Evidence from the use of artificial electron acceptors and donors. Using artificial electron donors and acceptors, it is shown here that the major HCO3- effect in the Hill reaction is after the \"primary\" electron acceptor (Q) of Photosystem II and before the site of action of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (at the plastoquinone pool). Chloroplasts in the presence of both 3-(3',4'-dichlorophenyl)-1,1-dimethylurea, which blocks electron flow from the reduced primary acdeptor Q- to the plastoquinone pool, and silicomolybdate, which accepts electrons from Q-, show no significant bicarbonate stimulation of electron flow. However, a 6-7 fold stimulation is clearly observed when oxidized diaminodurene, as an electron acceptor, and dibromothymoquinone, as an inhibitor of electron flow beyond the plastoquinone pool, are used. In the same chloroplast preparation no measurable effect of bicarbonate is observed in a Photosystem I reaction as monitored by electron flow from reduced diaminodurene to methyl viologen in the presence of 3- (3',4'-dichlorophenyl)-1,1-dimethylurea. The insensitivity of the bicarbonate effect to uncouplers of photophosphorylation and the dependence of this effect on the presence of a weak acid anion and on external pH are also reported."}
{"id": "PMID:20950", "title": "Interactions of Tetrahymena dynein with microtubule protein. Tubulin-induced stimulation of dynein ATPase activity.", "content": "The ATPase (EC 3.6.1.3) activity of 30 S dynein from Tetrahymena cilia was remarkably stimulated by porcine brain tubulin at pH 10. The activity increased with increasing concentration of tubulin until the molar ratio of tubulin dimer to 30 S dynein reached approx. 10. The optimum of the ATPase activity of 30 S dynein in the presence of tubulin was 1-2 mM for MgCl2 and 2 mM for CaCl2. Increasing ionic strength gradually inhibited the stimulation effects of tubulin. Activation energies of 30 S dynein in the presence and absence of tubulin were almost the same. At the temperatures beyond 25 degrees C stimulation effects of tubulin disappeared. ATP was a specific substrate even in the presence of tubulin. In kinetic investigations parallel reciprocal plots were observed in a constant ratio of divalent cations to ATP of 2, indicating that tubulin was less tightly bound to 30 S dynein in the presence of ATP than the absence. The similar results were obtained at pH 8.2. 14 S dynein and the 12 S fragment which have poor ability to recombine with outer fibers were also activated with brain tubulin.", "contents": "Interactions of Tetrahymena dynein with microtubule protein. Tubulin-induced stimulation of dynein ATPase activity. The ATPase (EC 3.6.1.3) activity of 30 S dynein from Tetrahymena cilia was remarkably stimulated by porcine brain tubulin at pH 10. The activity increased with increasing concentration of tubulin until the molar ratio of tubulin dimer to 30 S dynein reached approx. 10. The optimum of the ATPase activity of 30 S dynein in the presence of tubulin was 1-2 mM for MgCl2 and 2 mM for CaCl2. Increasing ionic strength gradually inhibited the stimulation effects of tubulin. Activation energies of 30 S dynein in the presence and absence of tubulin were almost the same. At the temperatures beyond 25 degrees C stimulation effects of tubulin disappeared. ATP was a specific substrate even in the presence of tubulin. In kinetic investigations parallel reciprocal plots were observed in a constant ratio of divalent cations to ATP of 2, indicating that tubulin was less tightly bound to 30 S dynein in the presence of ATP than the absence. The similar results were obtained at pH 8.2. 14 S dynein and the 12 S fragment which have poor ability to recombine with outer fibers were also activated with brain tubulin."}
{"id": "PMID:20951", "title": "Non-covalent cross-linking of lipid bilayers by myelin basic protein: a possible role in myelin formation.", "content": "Myelin basic protein associates with bilayer vesicles of pure egg phosphatidylcholine, L-alpha-dimyristoyl phosphatidylcholine and DL-alpha-dipalmitoyl phosphatidylcholine. Under optimum conditions the vesicles contain 15-18% of protein by weight. The binding to dipalmitoyl phosphatidylcholine is facilitated above its gel-to-liquid crystalline transition temperature. At low ionic strength the protein provokes a large increase in vesicle size and aggregation of these enlarged vesicles. Above a sodium chloride concentration of 0.07 M vesicle fusion is far less marked but aggregation persists. The pH- and ionic strength-dependence of this aggregation follows that of the protein alone; in both cases it occurs despite appreciable electrostatic repulsion between the associated species. A similar interaction was observed with diacyl phosphatidylserine vesicles. These observations, which contrast with earlier reports in the literature of a lack of binding of basic protein to phosphatidylcholine-containing lipids, demonstrate the ability of this protein to interact non-ionically with lipid bilayers. The strong cross-linking of lipid bilayers suggests a role for basic protein in myelin, raising the possibility that the protein is instrumental in collapsing the oligodendrocyte cell membrane and thus initiating myelin formation.", "contents": "Non-covalent cross-linking of lipid bilayers by myelin basic protein: a possible role in myelin formation. Myelin basic protein associates with bilayer vesicles of pure egg phosphatidylcholine, L-alpha-dimyristoyl phosphatidylcholine and DL-alpha-dipalmitoyl phosphatidylcholine. Under optimum conditions the vesicles contain 15-18% of protein by weight. The binding to dipalmitoyl phosphatidylcholine is facilitated above its gel-to-liquid crystalline transition temperature. At low ionic strength the protein provokes a large increase in vesicle size and aggregation of these enlarged vesicles. Above a sodium chloride concentration of 0.07 M vesicle fusion is far less marked but aggregation persists. The pH- and ionic strength-dependence of this aggregation follows that of the protein alone; in both cases it occurs despite appreciable electrostatic repulsion between the associated species. A similar interaction was observed with diacyl phosphatidylserine vesicles. These observations, which contrast with earlier reports in the literature of a lack of binding of basic protein to phosphatidylcholine-containing lipids, demonstrate the ability of this protein to interact non-ionically with lipid bilayers. The strong cross-linking of lipid bilayers suggests a role for basic protein in myelin, raising the possibility that the protein is instrumental in collapsing the oligodendrocyte cell membrane and thus initiating myelin formation."}
{"id": "PMID:20952", "title": "Contrast manifestation of alkaline phosphatase and 5'-nucleotidase in plasma membranes isolated from rat liver and ascites hepatoma.", "content": "1. Plasma membranes were isolated from ascites hepatoma AH-130 and rat livers with or without partial hepatectomy or bile duct ligation. Reciprocal manifestations of two marker enzymes for plasma membranes were observed in these membrane preparations; alkaline phosphatase activity was found much higher in the hepatoma membrane than in any preparations of the liver membranes, whereas 5'-nucleotidase activity was much lower in the former than in the latter. 2. Effects of lectins and anti-plasma membrane antiserum on these two marker enzymes were examined. The results showed that about 50% of apparent activity of 5'-nucleotidase found in the hepatoma membrane was exhibited by alkaline phosphatase. 3. Localizations of alkaline phosphatase and 5'-nucleotidase in polyacrylamide gels after electrophoresis were demonstrated using 5'-AMP and 5-Br, 4-Cl-indoxylphosphate as substrate. There was a difference in electrophoretic mobility between the alkaline phosphatase of the hepatoma and that of the liver.", "contents": "Contrast manifestation of alkaline phosphatase and 5'-nucleotidase in plasma membranes isolated from rat liver and ascites hepatoma. 1. Plasma membranes were isolated from ascites hepatoma AH-130 and rat livers with or without partial hepatectomy or bile duct ligation. Reciprocal manifestations of two marker enzymes for plasma membranes were observed in these membrane preparations; alkaline phosphatase activity was found much higher in the hepatoma membrane than in any preparations of the liver membranes, whereas 5'-nucleotidase activity was much lower in the former than in the latter. 2. Effects of lectins and anti-plasma membrane antiserum on these two marker enzymes were examined. The results showed that about 50% of apparent activity of 5'-nucleotidase found in the hepatoma membrane was exhibited by alkaline phosphatase. 3. Localizations of alkaline phosphatase and 5'-nucleotidase in polyacrylamide gels after electrophoresis were demonstrated using 5'-AMP and 5-Br, 4-Cl-indoxylphosphate as substrate. There was a difference in electrophoretic mobility between the alkaline phosphatase of the hepatoma and that of the liver."}
{"id": "PMID:20953", "title": "Partition of catalase and its peroxidase activities in human red cell membrane: effect of ATP depletion.", "content": "Partititon of catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase EC 1.11.1.6) and peroxidase (donor:hydrogen-peroxide oxidoreductase EC 1.11.1.7) activities between the red cell membrane and the cytosol were studied under various experimental conditions. A small but significant amount of catalase (1.6%) was retained on human red cell membranes prepared by hemolysing washed red cells with 30 volumes of 10 mM Tris buffer, pH 7.4. Membrane -bound catalase had a relatively higher peroxidase activity than the soluble enzyme fraction. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate of the solubilized membranes demonstrated catalase to be a single band with a molecular weight of 60 000. Membranes prepared from adenosine triphosphate-depleted red cells depicted a two to three-fold increase in catalase activity, as well as an increase in 60 000 molecular weight band on polyacrylamide gel electrophoresis. The extra amount of retained catalase was a less efficient peroxidase than found in fresh membranes. The binding of catalase to ATP-depleted red cell membranes was dependent upon both pH and hemolysing ratio. Red cells incubated at pH 7.1 demonstrated a decrease in bound catalase, as did membranes prepared from red cells hemolysed at 1:100 dilution. beta-Mercaptoethanol decreased the catalase activity in the membranes and increased the odianisidine peroxidase activity without any significant effect on the 60 000-dalton band.", "contents": "Partition of catalase and its peroxidase activities in human red cell membrane: effect of ATP depletion. Partititon of catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase EC 1.11.1.6) and peroxidase (donor:hydrogen-peroxide oxidoreductase EC 1.11.1.7) activities between the red cell membrane and the cytosol were studied under various experimental conditions. A small but significant amount of catalase (1.6%) was retained on human red cell membranes prepared by hemolysing washed red cells with 30 volumes of 10 mM Tris buffer, pH 7.4. Membrane -bound catalase had a relatively higher peroxidase activity than the soluble enzyme fraction. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate of the solubilized membranes demonstrated catalase to be a single band with a molecular weight of 60 000. Membranes prepared from adenosine triphosphate-depleted red cells depicted a two to three-fold increase in catalase activity, as well as an increase in 60 000 molecular weight band on polyacrylamide gel electrophoresis. The extra amount of retained catalase was a less efficient peroxidase than found in fresh membranes. The binding of catalase to ATP-depleted red cell membranes was dependent upon both pH and hemolysing ratio. Red cells incubated at pH 7.1 demonstrated a decrease in bound catalase, as did membranes prepared from red cells hemolysed at 1:100 dilution. beta-Mercaptoethanol decreased the catalase activity in the membranes and increased the odianisidine peroxidase activity without any significant effect on the 60 000-dalton band."}
{"id": "PMID:20955", "title": "Polyribonucleotides containing thiopurines. Synthesis and properties of poly(1-methyl-6-thioguanylic acid).", "content": "The synthesis of 1-methyl-6-thioguanosine 5'-diphosphate and its conversion to poly(1-methyl-6-thioguanylic acid) by means of polynucleotide phosphorylase are described. The polymer exhibited cooperative behavior (Tm = 294 K in the absence of added NaCl) characteristic of a highly stacked single-stranded helical array. In a high salt environment (0.5 M NaCl) the melting was much less cooperative and gave a higher Tm (313 K); this is suggestive of interstrand aggregation involving hydrogen bonding. The polynucleotide exhibited a remarkably high pKa (6.2) compared to that of the mononucleotide (2.6), and formed a very stable acid structure (Tm = 356 K in 50% ethylene glycol). Comparisons with poly(1-methyl-6-thioinosinic acid) and poly(6-thioguanylic acid) establish that both the 2-amino group and the 1-methyl group are required for the formation of the stable acid structure.", "contents": "Polyribonucleotides containing thiopurines. Synthesis and properties of poly(1-methyl-6-thioguanylic acid). The synthesis of 1-methyl-6-thioguanosine 5'-diphosphate and its conversion to poly(1-methyl-6-thioguanylic acid) by means of polynucleotide phosphorylase are described. The polymer exhibited cooperative behavior (Tm = 294 K in the absence of added NaCl) characteristic of a highly stacked single-stranded helical array. In a high salt environment (0.5 M NaCl) the melting was much less cooperative and gave a higher Tm (313 K); this is suggestive of interstrand aggregation involving hydrogen bonding. The polynucleotide exhibited a remarkably high pKa (6.2) compared to that of the mononucleotide (2.6), and formed a very stable acid structure (Tm = 356 K in 50% ethylene glycol). Comparisons with poly(1-methyl-6-thioinosinic acid) and poly(6-thioguanylic acid) establish that both the 2-amino group and the 1-methyl group are required for the formation of the stable acid structure."}
{"id": "PMID:20956", "title": "Biphasic effects of translational inhibitors on liver tyrosine aminotransferase.", "content": "Low doses of cycloheximide or emetine cause rat liver tyrosine aminotransferase activity to rise up to twice the control levels in 2 h. By contrast, in the same interval no changes, or only a slight decrease, are produced by either drug at high dosage. Adrenalectomised animals display the same pattern of response. High doses of either antibiotic virtually afford a complete inhibition of 14C-labelled amino acid incorporation into liver and plasma proteins, whereas no more than a 30% decrease is observed with low doses. When administered in the course of the induction by cortisol, high doses of inhibitor prevent any further change in tyrosine aminotransferase activity, stabilising it at the level already attained; low doses, while slightly affecting the synthetic phase evoked by cortisol, drastically interfere with the deinduction. Six hours after various doses of either inhibitor the tyrosine aminotransferase activity is markedly increased, this late effect being largely dependent on the presence of adrenals. The amino acid incorporating actitivy of the liver may exceed that of controls, as observed particularly after small doses of emetine.", "contents": "Biphasic effects of translational inhibitors on liver tyrosine aminotransferase. Low doses of cycloheximide or emetine cause rat liver tyrosine aminotransferase activity to rise up to twice the control levels in 2 h. By contrast, in the same interval no changes, or only a slight decrease, are produced by either drug at high dosage. Adrenalectomised animals display the same pattern of response. High doses of either antibiotic virtually afford a complete inhibition of 14C-labelled amino acid incorporation into liver and plasma proteins, whereas no more than a 30% decrease is observed with low doses. When administered in the course of the induction by cortisol, high doses of inhibitor prevent any further change in tyrosine aminotransferase activity, stabilising it at the level already attained; low doses, while slightly affecting the synthetic phase evoked by cortisol, drastically interfere with the deinduction. Six hours after various doses of either inhibitor the tyrosine aminotransferase activity is markedly increased, this late effect being largely dependent on the presence of adrenals. The amino acid incorporating actitivy of the liver may exceed that of controls, as observed particularly after small doses of emetine."}
{"id": "PMID:20957", "title": "Fluorimetric assay of tobacco leaf dehydrogenases with resazurin.", "content": "A versatile fluorimetric assay based on the reduction of resazurin to resorufin demonstrated high specific activities for a number of important pyridine nucleotide-linked dehydrogenases in tobacco leaves. The Michaelis constant for the important photosynthetic enzyme, D-glyceraldehyde-3-phosphate:NADP+ oxidoreductase (EC 1.2.1.13), determined by the fluorimetric method, was considerably lower than constants determined by conventional extraction and assay methods reported for the enzyme from other plants. The sensitivity of the fluorimetric method enabled the use of dilute enzyme preparations with resultant low background and high substrate specificity. Inclusion of the anti-oxidant diethyldithiocarbamate in the extraction medium preserved the enzymes during extraction. Primary amines inhibited competitively, and phenazine methosulfate non-competitively each of the eight dehydrogenases tested with the fluorimetric assay. The Mn2+ dependence of NADP-linked dehydrogenases specific for isocitrate and malate was confirmed. The method is rapid, requires a simple combination of ingredients and should be useful for surveying dehydrogenase activity in leaves.", "contents": "Fluorimetric assay of tobacco leaf dehydrogenases with resazurin. A versatile fluorimetric assay based on the reduction of resazurin to resorufin demonstrated high specific activities for a number of important pyridine nucleotide-linked dehydrogenases in tobacco leaves. The Michaelis constant for the important photosynthetic enzyme, D-glyceraldehyde-3-phosphate:NADP+ oxidoreductase (EC 1.2.1.13), determined by the fluorimetric method, was considerably lower than constants determined by conventional extraction and assay methods reported for the enzyme from other plants. The sensitivity of the fluorimetric method enabled the use of dilute enzyme preparations with resultant low background and high substrate specificity. Inclusion of the anti-oxidant diethyldithiocarbamate in the extraction medium preserved the enzymes during extraction. Primary amines inhibited competitively, and phenazine methosulfate non-competitively each of the eight dehydrogenases tested with the fluorimetric assay. The Mn2+ dependence of NADP-linked dehydrogenases specific for isocitrate and malate was confirmed. The method is rapid, requires a simple combination of ingredients and should be useful for surveying dehydrogenase activity in leaves."}
{"id": "PMID:20958", "title": "Purification and characterization of 2-oxoaldehyde dehydrogenase from rat liver.", "content": "The partial purification (123-fold) of 2-oxoaldehyde dehydrogenase (2-oxoaldehyde:NAD(P)+ oxidoreductase, 1.2.1.23) from rat liver was carried out using a purification procedure which involved (NH4)2SO4 fractionation, DEAE-Sephadex chromatography, Blue-Dextran affinity chromatography and CM-Sephadex chromatography. A single form of the enzyme was observed, mol. wt. approx. 50000 by gel chromatography. 2-Oxoaldehyde dehydrogenase appears to be highly specific for NADP+ and methylglyoxal. No activity is observed in the absence of certain amines which have vicinal amino and hydroxyl groups. The only known amine which activates the enzyme at physiological pH is L-serine methyl ester, suggesting that the regulation of this enzyme in vivo may require a derivative of serine.", "contents": "Purification and characterization of 2-oxoaldehyde dehydrogenase from rat liver. The partial purification (123-fold) of 2-oxoaldehyde dehydrogenase (2-oxoaldehyde:NAD(P)+ oxidoreductase, 1.2.1.23) from rat liver was carried out using a purification procedure which involved (NH4)2SO4 fractionation, DEAE-Sephadex chromatography, Blue-Dextran affinity chromatography and CM-Sephadex chromatography. A single form of the enzyme was observed, mol. wt. approx. 50000 by gel chromatography. 2-Oxoaldehyde dehydrogenase appears to be highly specific for NADP+ and methylglyoxal. No activity is observed in the absence of certain amines which have vicinal amino and hydroxyl groups. The only known amine which activates the enzyme at physiological pH is L-serine methyl ester, suggesting that the regulation of this enzyme in vivo may require a derivative of serine."}
{"id": "PMID:20959", "title": "Oxidation of hypoxanthines, bearing 8-aryl or 8-pyridyl substituents, by bovine milk xanthine oxidase.", "content": "1. Hypoxanthines, bearing at position 8 aryl or pyridyl substituents, are converted by bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2) into the corresponding xanthines at low rates. Oxidation is accelerated considerably when the 8-pyridyl substituents are quaternised. 2. In the enzymic oxidation of quaternary 8-pyridylhypoxanthines a lag phase precedes the attainment of a constant, maximal reaction rate. It is assumed that the delay is due to a relatively slow conformational change in the active enzymic center. 3. In 8-(3'-N-methylpyridinio)xanthine betaine, also the pyridinium moiety is attacked at high pH (9-11) to yield an N-methyl-2-pyridone. The analogous pyridone is the only oxidation product of 1-methyl-8-(3'-N-methylpyridinio)-hypoxanthine betaine, which is not attacked in the pyrimidine ring. 4. The cationic substrates are attracted to the enzyme by an anionic group, which probably forms an ion pair with a protonated amino group in or near the active center.", "contents": "Oxidation of hypoxanthines, bearing 8-aryl or 8-pyridyl substituents, by bovine milk xanthine oxidase. 1. Hypoxanthines, bearing at position 8 aryl or pyridyl substituents, are converted by bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2) into the corresponding xanthines at low rates. Oxidation is accelerated considerably when the 8-pyridyl substituents are quaternised. 2. In the enzymic oxidation of quaternary 8-pyridylhypoxanthines a lag phase precedes the attainment of a constant, maximal reaction rate. It is assumed that the delay is due to a relatively slow conformational change in the active enzymic center. 3. In 8-(3'-N-methylpyridinio)xanthine betaine, also the pyridinium moiety is attacked at high pH (9-11) to yield an N-methyl-2-pyridone. The analogous pyridone is the only oxidation product of 1-methyl-8-(3'-N-methylpyridinio)-hypoxanthine betaine, which is not attacked in the pyrimidine ring. 4. The cationic substrates are attracted to the enzyme by an anionic group, which probably forms an ion pair with a protonated amino group in or near the active center."}
{"id": "PMID:20960", "title": "Evidence about the catecholoxidase activity of the enzyme ascorbate oxidase extracted from Cucurbita pepo medullosa.", "content": "Pure ascorbate oxidase (L-ascorbate:oxygen oxidoreductase, EC 1.10.3.3) isolated from Cucurbita pepo medullosa, which is known to be specific for ascorbic acid, shows a secondary catecholoxidase activity at approx. pH 6.7. This activity was tested against natural and synthetic compounds possessing a catechol-like structure. Among natural compounds (+)-catechin furnishes the same complex oxidation mixture obtained with other oxidases. Among synthetic compounds, 3,5-di-t-butylcatechol and 4-t-butylcatechol give the corresponding o-quinones. The significance of this secondary activity in the darkening process of fruits and vegetables which contain ascorbate oxidase is also discussed.", "contents": "Evidence about the catecholoxidase activity of the enzyme ascorbate oxidase extracted from Cucurbita pepo medullosa. Pure ascorbate oxidase (L-ascorbate:oxygen oxidoreductase, EC 1.10.3.3) isolated from Cucurbita pepo medullosa, which is known to be specific for ascorbic acid, shows a secondary catecholoxidase activity at approx. pH 6.7. This activity was tested against natural and synthetic compounds possessing a catechol-like structure. Among natural compounds (+)-catechin furnishes the same complex oxidation mixture obtained with other oxidases. Among synthetic compounds, 3,5-di-t-butylcatechol and 4-t-butylcatechol give the corresponding o-quinones. The significance of this secondary activity in the darkening process of fruits and vegetables which contain ascorbate oxidase is also discussed."}
{"id": "PMID:20962", "title": "Canine thyroid fucokinase.", "content": "A radiometric assay was developed for fucokinase (ATP:6-deoxy-L-galactose 1-phosphotransferase, EC 2.7.1.52) based on the conversion of L-[14C]fucose to L-[14C]fucose 1-phosphate which is trapped and counted on ion exchange paper. This assay was used to detect the presence of a fucokinase in canine thyroid tissue which was subsequently purified 2754-fold over the crude tissue extracts. The product of the fucokinase was identified as the beta-anomer. The pH versus activity curve for the enzyme appears biphasic with optima at pH 6.5 and pH 8.25. The enzyme was shown to be highly specific for L-fucose with a Km of 2.6 - 10(-5) M at pH 8.25. It was shown to be absolutely specific for ATP as a phosphate donor with a Km of 6.3 - 10(-4) M at pH 8.25. The enzyme requires a divalent cation. Mg2+ is slightly more effective than Mn2+ in meeting this need. The molecular weight of the enzyme has been determined to be 494 000 +/- 12 400.", "contents": "Canine thyroid fucokinase. A radiometric assay was developed for fucokinase (ATP:6-deoxy-L-galactose 1-phosphotransferase, EC 2.7.1.52) based on the conversion of L-[14C]fucose to L-[14C]fucose 1-phosphate which is trapped and counted on ion exchange paper. This assay was used to detect the presence of a fucokinase in canine thyroid tissue which was subsequently purified 2754-fold over the crude tissue extracts. The product of the fucokinase was identified as the beta-anomer. The pH versus activity curve for the enzyme appears biphasic with optima at pH 6.5 and pH 8.25. The enzyme was shown to be highly specific for L-fucose with a Km of 2.6 - 10(-5) M at pH 8.25. It was shown to be absolutely specific for ATP as a phosphate donor with a Km of 6.3 - 10(-4) M at pH 8.25. The enzyme requires a divalent cation. Mg2+ is slightly more effective than Mn2+ in meeting this need. The molecular weight of the enzyme has been determined to be 494 000 +/- 12 400."}
{"id": "PMID:20963", "title": "The mode of binding of potential transition-state analogs to acetylcholinesterase.", "content": "Phenylacetone, 4-phenyl-2-butanone, and 4-oxopentyltrimethylammonium chloride were tested as potential transition state analogs for eel acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7). Phenylacetone is a competitive inhibitor of the enzyme but not a transition state analog, since its binding constant is similar to that for the substrate phenyl acetate. 4-Phenyl-2-butanone binds 6-18 times more tightly than the inhibitors 4-phenyl-2-butanol and N-benzylacetamide and the substrate benzyl acetate and also blocks inactivation of the enzyme with methanesulfonyl fluoride. However, its binding is independent of pH in the range 5-7.5, whereas both V and V/Km for benzyl acetate hydrolysis decrease with decreasing pH in this range. These data indicate a specific but weak interaction between the ketone carbonyl and the enzyme, but probably do not justify considering this compound a transition state analog. 4-oxopentyltrimethylammonium iodide has previously been shown to bind about 125 times more strongly than the substrate acetylcholamine. It also binds about 375 times more strongly than the alcohol 4-hydroxypentyltrimethylammonium iodide. Furthermore, the ketone protects the enzyme from inactivation by methansulfony fluoride, while the corresponding quaternary ammonium alcohol accelerates this inactivation reaction. This additional information confirms that the ketone is a transition state analog.", "contents": "The mode of binding of potential transition-state analogs to acetylcholinesterase. Phenylacetone, 4-phenyl-2-butanone, and 4-oxopentyltrimethylammonium chloride were tested as potential transition state analogs for eel acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7). Phenylacetone is a competitive inhibitor of the enzyme but not a transition state analog, since its binding constant is similar to that for the substrate phenyl acetate. 4-Phenyl-2-butanone binds 6-18 times more tightly than the inhibitors 4-phenyl-2-butanol and N-benzylacetamide and the substrate benzyl acetate and also blocks inactivation of the enzyme with methanesulfonyl fluoride. However, its binding is independent of pH in the range 5-7.5, whereas both V and V/Km for benzyl acetate hydrolysis decrease with decreasing pH in this range. These data indicate a specific but weak interaction between the ketone carbonyl and the enzyme, but probably do not justify considering this compound a transition state analog. 4-oxopentyltrimethylammonium iodide has previously been shown to bind about 125 times more strongly than the substrate acetylcholamine. It also binds about 375 times more strongly than the alcohol 4-hydroxypentyltrimethylammonium iodide. Furthermore, the ketone protects the enzyme from inactivation by methansulfony fluoride, while the corresponding quaternary ammonium alcohol accelerates this inactivation reaction. This additional information confirms that the ketone is a transition state analog."}
{"id": "PMID:20964", "title": "pH dependence and solvent isotope effects in the hydrolysis of phosphomonoesters by human prostatic acid phosphatase.", "content": "The pH dependence of the human prostatic acid phosphatase-catalyzed hydrolysis of p-nitrophenyl phosphate and beta-glyceryl phosphate has been studied over a wide range of pH and the values of Km and V calculated with the aid of the Cleland HYPER program. The pH dependence of Km shows the effect of substrate ionization: pK values of 5.6 and 6.4 are observed as for the respective values of free substrates. The pH dependence of both Km and V for each substrate reveals the involvement of an ionizable group in the ES complex which is ascribed to a phosphohistidine-enzyme intermediate. The small deuterium solvent isotope effects which are observed on V are consistent with values observed for solvolysis of phosphoramidates. The measured data for Km indicates limits on burst-titration experiments of prostatic acid phosphatase (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.2).", "contents": "pH dependence and solvent isotope effects in the hydrolysis of phosphomonoesters by human prostatic acid phosphatase. The pH dependence of the human prostatic acid phosphatase-catalyzed hydrolysis of p-nitrophenyl phosphate and beta-glyceryl phosphate has been studied over a wide range of pH and the values of Km and V calculated with the aid of the Cleland HYPER program. The pH dependence of Km shows the effect of substrate ionization: pK values of 5.6 and 6.4 are observed as for the respective values of free substrates. The pH dependence of both Km and V for each substrate reveals the involvement of an ionizable group in the ES complex which is ascribed to a phosphohistidine-enzyme intermediate. The small deuterium solvent isotope effects which are observed on V are consistent with values observed for solvolysis of phosphoramidates. The measured data for Km indicates limits on burst-titration experiments of prostatic acid phosphatase (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.2)."}
{"id": "PMID:20966", "title": "Proton magnetic resonance studies of histidines in human, rhesus monkey, and bovine carbonic anhydrases.", "content": "Histidine C-2 proton resonances in rhesus monkey carbonic anhydrase B (carbonate hydro-lyase, EC 4.2.1.1) and bovine carbonic anhydrase were investigated using 270-MHz proton magnetic resonance. The results suggest that there are extensive three-dimensional homologies between the human B and rhesus B enzymes and between the human C and bovine enzymes. Resonances from solvent exchangeable protons have been observed in the 11-16 ppm range in the NMR spectra of human carbonic anhydrases B and C and bovine carbonic anhydrase. Up to five of these are sensitive to changes of pH and the presence of inhibitors. Three of these resonances are assigned to NH protons of the metal coordinated imidazole groups. These results are discussed in relation to various models for the catalytic mechanism of carbonic anhydrase.", "contents": "Proton magnetic resonance studies of histidines in human, rhesus monkey, and bovine carbonic anhydrases. Histidine C-2 proton resonances in rhesus monkey carbonic anhydrase B (carbonate hydro-lyase, EC 4.2.1.1) and bovine carbonic anhydrase were investigated using 270-MHz proton magnetic resonance. The results suggest that there are extensive three-dimensional homologies between the human B and rhesus B enzymes and between the human C and bovine enzymes. Resonances from solvent exchangeable protons have been observed in the 11-16 ppm range in the NMR spectra of human carbonic anhydrases B and C and bovine carbonic anhydrase. Up to five of these are sensitive to changes of pH and the presence of inhibitors. Three of these resonances are assigned to NH protons of the metal coordinated imidazole groups. These results are discussed in relation to various models for the catalytic mechanism of carbonic anhydrase."}
{"id": "PMID:20967", "title": "Kinetic analysis of calcium activation of brain acetylcholinesterase forms.", "content": "Calcium activation of acetylcholine hydrolysis by bovine brain acetylcholinesterase (Acetylcholine hydrolase, EC 3.1.1.7) forms has been analyzed in terms of changes in kinetic constants and thermodynamic activation parameters. De-acetylation was determined to be the major rate-influencing step in acetylcholine hydrolysis by both 60 000- and 240 000-dalton forms of the brain enzyme and 10 mM Ca2+ increased the rate constant for this step (k+3) by approximately 30% for both forms. For the smaller acetylcholinesterase form the effects of Ca2+ on de-acetylation was equivalent to its effect on the overall rate constant (k) and occurred without an effect on pK. In the case of the 240 000-dalton species, the overall rate constant was increased by Ca2+ by 33% at pH 8.0 and 81% at pH 7.25 and involved a pK shift of -0.2 pH units. For both enzyme forms the rate constants for acetylation (k+2) were increased by Ca2+. Thermodynamic analysis suggested that Ca2+ activation of the acetylation step was entropically driven. Differences between the two enzymes forms in terms of Ca2+ appear to result from association of low molecular weight species.", "contents": "Kinetic analysis of calcium activation of brain acetylcholinesterase forms. Calcium activation of acetylcholine hydrolysis by bovine brain acetylcholinesterase (Acetylcholine hydrolase, EC 3.1.1.7) forms has been analyzed in terms of changes in kinetic constants and thermodynamic activation parameters. De-acetylation was determined to be the major rate-influencing step in acetylcholine hydrolysis by both 60 000- and 240 000-dalton forms of the brain enzyme and 10 mM Ca2+ increased the rate constant for this step (k+3) by approximately 30% for both forms. For the smaller acetylcholinesterase form the effects of Ca2+ on de-acetylation was equivalent to its effect on the overall rate constant (k) and occurred without an effect on pK. In the case of the 240 000-dalton species, the overall rate constant was increased by Ca2+ by 33% at pH 8.0 and 81% at pH 7.25 and involved a pK shift of -0.2 pH units. For both enzyme forms the rate constants for acetylation (k+2) were increased by Ca2+. Thermodynamic analysis suggested that Ca2+ activation of the acetylation step was entropically driven. Differences between the two enzymes forms in terms of Ca2+ appear to result from association of low molecular weight species."}
{"id": "PMID:20969", "title": "Resolution of independently titrating spectral components in the ultraviolet circular dichroism of subtilisin enzymes by matrix rank analysis.", "content": "The ultraviolet circular dichroism of di-isopropylphophoryl-subtilisins Carlsberg and Novo (EC 3.4.21.14) has been examined as a function of pH. The CD of these enzymes below 260 nm is invariant over the pH interval 4 to 12, below or above which spectral changes occur suggesting a transition to a random coil form. Above pH 8 contributions due to the ionization of tyrosyl residues appear in the CD above 260 nm as bands shifted to longer wavelengths. Three independently titratable components, obtained by matrix rank analysis, account for the observed CD spectral changes above 260 nm of Dip-subtilisin Carlsberg in the pH interval 8 to 12. By contrast, two components were derived for the Novo enzyme. The identities of the matrix rank components were surmised from their apparent pKa values. One component of both subtilisin enzymes corresponds to the CD of the \"buried\" or irreversibly titratable tyrosyl residues of the enzyme. The other matrix rank components correspond to the CD of the \"exposed\" or freely ionizable tyrosyl residues. These residues are optically active only in the ionized state. Two types of \"exposed\" tyrosyl residues, arising because of differing sensitivity to the ionization of the \"partially buried\" or abnormally titrating tyrosyl residues, are evident in Dip-subtilisin Carlsberg. A pH-induced local conformational change in this enzyme is proposed to account for this behavior. The \"partially buried\" tyrosyl residues of both subtilisins appear to be devoid of optical activity in either the tyrosyl or tyrosylate form.", "contents": "Resolution of independently titrating spectral components in the ultraviolet circular dichroism of subtilisin enzymes by matrix rank analysis. The ultraviolet circular dichroism of di-isopropylphophoryl-subtilisins Carlsberg and Novo (EC 3.4.21.14) has been examined as a function of pH. The CD of these enzymes below 260 nm is invariant over the pH interval 4 to 12, below or above which spectral changes occur suggesting a transition to a random coil form. Above pH 8 contributions due to the ionization of tyrosyl residues appear in the CD above 260 nm as bands shifted to longer wavelengths. Three independently titratable components, obtained by matrix rank analysis, account for the observed CD spectral changes above 260 nm of Dip-subtilisin Carlsberg in the pH interval 8 to 12. By contrast, two components were derived for the Novo enzyme. The identities of the matrix rank components were surmised from their apparent pKa values. One component of both subtilisin enzymes corresponds to the CD of the \"buried\" or irreversibly titratable tyrosyl residues of the enzyme. The other matrix rank components correspond to the CD of the \"exposed\" or freely ionizable tyrosyl residues. These residues are optically active only in the ionized state. Two types of \"exposed\" tyrosyl residues, arising because of differing sensitivity to the ionization of the \"partially buried\" or abnormally titrating tyrosyl residues, are evident in Dip-subtilisin Carlsberg. A pH-induced local conformational change in this enzyme is proposed to account for this behavior. The \"partially buried\" tyrosyl residues of both subtilisins appear to be devoid of optical activity in either the tyrosyl or tyrosylate form."}
{"id": "PMID:20971", "title": "Some characteristics of soluble fatty acid synthesis in germinating pea seeds.", "content": "Soluble fractions from germinating pea synthesize palmitic acid de novo and stearic acid by elongation. Malonyl CoA, acyl carrier protein and NADPH are required for both reactions. In contrast to some other plant systems, no requirement was found for divalent cations. On the other hand, the formation of both stearate and palmitate was inhibited by sulphydryl reagents and palmitate elongation was sensitive to arsenite. The products of the reactions were examined and found to be principally acyl-acyl carrier proteins and unesterified fatty acids. Unlike the pea microsomal fractions, the soluble enzymes are stimulated only slightly by the addition of exogenous lipids. The substrate for palmitate elongation is palmitoylacyl carrier protein, which is quantitatively elongated to stearate. Comparisons are made with membrane-localised fatty acid synthesis from the same tissue.", "contents": "Some characteristics of soluble fatty acid synthesis in germinating pea seeds. Soluble fractions from germinating pea synthesize palmitic acid de novo and stearic acid by elongation. Malonyl CoA, acyl carrier protein and NADPH are required for both reactions. In contrast to some other plant systems, no requirement was found for divalent cations. On the other hand, the formation of both stearate and palmitate was inhibited by sulphydryl reagents and palmitate elongation was sensitive to arsenite. The products of the reactions were examined and found to be principally acyl-acyl carrier proteins and unesterified fatty acids. Unlike the pea microsomal fractions, the soluble enzymes are stimulated only slightly by the addition of exogenous lipids. The substrate for palmitate elongation is palmitoylacyl carrier protein, which is quantitatively elongated to stearate. Comparisons are made with membrane-localised fatty acid synthesis from the same tissue."}
{"id": "PMID:20974", "title": "Immunoelectrophoretic studies on pig intestinal brush border proteins.", "content": "Brush borders were prepared from pig intestinal mucosa and the membrane proteins solubilized with either Triton X-100 or papain. Proteins, thus released, were used as antigens to raise antisera in rabbits. The immunoglobulin G fractions were isolated and shown by the double layer immunofluorescence staining technique to react only with the brush border region of the enterocyte. The antibodies obtained were used in immunoelectrophoretic studies on the brush border proteins. Eight hydrolytic activities were identified by the use of histo-chemical staining methods. These were the microsomal aminopeptidase (EC 3.4.11.2), aspartate aminopeptidase (EC 3.4.11.7), dipeptidyl peptidase IV (EC 3.4.14.X), lactase (EC 3.2.1.23), glucoamylase (EC 3.2.1.3), sucrase (EC 3.2.1.48), isomaltase (EC 3.2.1.10) and alkaline phosphatase (EC 3.1.3.1). In addition, at least four faint immunoprecipitates were formed but none of these were identified.", "contents": "Immunoelectrophoretic studies on pig intestinal brush border proteins. Brush borders were prepared from pig intestinal mucosa and the membrane proteins solubilized with either Triton X-100 or papain. Proteins, thus released, were used as antigens to raise antisera in rabbits. The immunoglobulin G fractions were isolated and shown by the double layer immunofluorescence staining technique to react only with the brush border region of the enterocyte. The antibodies obtained were used in immunoelectrophoretic studies on the brush border proteins. Eight hydrolytic activities were identified by the use of histo-chemical staining methods. These were the microsomal aminopeptidase (EC 3.4.11.2), aspartate aminopeptidase (EC 3.4.11.7), dipeptidyl peptidase IV (EC 3.4.14.X), lactase (EC 3.2.1.23), glucoamylase (EC 3.2.1.3), sucrase (EC 3.2.1.48), isomaltase (EC 3.2.1.10) and alkaline phosphatase (EC 3.1.3.1). In addition, at least four faint immunoprecipitates were formed but none of these were identified."}
{"id": "PMID:20976", "title": "Properties of trout hemoglobin covalently bound to a solid matrix.", "content": "This paper reports the ligand binding properties of the major hemoglobin component from trout (Salmo irideus) covalently bound to a solid matrix (Sepharose or Sephadex). A comparison between the functional properties of this protein in solution and of the protein-matrix complex shows significant changes although the basic properties of the molecule are maintained on covalent binding to Sepharose (or Sephadex). Thus the Root effect, characteristic of Hb trout IV, is still present while the heme-heme interactions are, on the average, smaller in the matrix bound protein as compared to the soluble form. No differences in the O2 binding properties were observed when the protein was coupled to the resin, as the ligand bound or as the ligand free derivative. Although an unequivocal interpretation of the data is made difficult by the lack of information on the number and identity of the groups involved in the coupling, the main changes in the protein functional properties may be related to the chemical modifications \"per se\" more than to the immobilization imposed to the macromolecule by coupling to the matrix. Structural changes which mainly involve perturbation of the tertiary structure of the molecule may qualitatively rationalize the data.", "contents": "Properties of trout hemoglobin covalently bound to a solid matrix. This paper reports the ligand binding properties of the major hemoglobin component from trout (Salmo irideus) covalently bound to a solid matrix (Sepharose or Sephadex). A comparison between the functional properties of this protein in solution and of the protein-matrix complex shows significant changes although the basic properties of the molecule are maintained on covalent binding to Sepharose (or Sephadex). Thus the Root effect, characteristic of Hb trout IV, is still present while the heme-heme interactions are, on the average, smaller in the matrix bound protein as compared to the soluble form. No differences in the O2 binding properties were observed when the protein was coupled to the resin, as the ligand bound or as the ligand free derivative. Although an unequivocal interpretation of the data is made difficult by the lack of information on the number and identity of the groups involved in the coupling, the main changes in the protein functional properties may be related to the chemical modifications \"per se\" more than to the immobilization imposed to the macromolecule by coupling to the matrix. Structural changes which mainly involve perturbation of the tertiary structure of the molecule may qualitatively rationalize the data."}
{"id": "PMID:20977", "title": "Resonance Raman study of the pH-dependent and detergent-induced structural alterations in the heme moiety of Rhodospirillum rubrum cytochrome c'.", "content": "The resonance Raman spectra and the structures of the heme moiety of Rhodospirillum rubrum cytochrome c' were investigated for its five states characterized by absorption spectra; Types-a and -n of the reduced form and Types-I, -II, and -III of the oxidized form. The frequency of the ligand-sensitive Raman line suggested the coordination of lysine (Nepsilon) at the sixth position of the heme iron of Type-n. The sixth ligand of Type-III was deduced to be either lysine or histidine but would not be methionine. Type-a and Type-II gave the Raman spectra of rather normal high spin type but Type-I was unusual in the sense that the frequencies of the Raman lines associated primarily with methine-bridge CC-stretching vibrations were relatively high in comparison with those of other high spin hemoproteins. Type-I was converted directly to Type-III upon the addition of SDS or 2-propanol but the conversion occurred via Type-II when pH was increased. Structural difference between the high spin hemes of Type-I and Type-II was discussed in detail.", "contents": "Resonance Raman study of the pH-dependent and detergent-induced structural alterations in the heme moiety of Rhodospirillum rubrum cytochrome c'. The resonance Raman spectra and the structures of the heme moiety of Rhodospirillum rubrum cytochrome c' were investigated for its five states characterized by absorption spectra; Types-a and -n of the reduced form and Types-I, -II, and -III of the oxidized form. The frequency of the ligand-sensitive Raman line suggested the coordination of lysine (Nepsilon) at the sixth position of the heme iron of Type-n. The sixth ligand of Type-III was deduced to be either lysine or histidine but would not be methionine. Type-a and Type-II gave the Raman spectra of rather normal high spin type but Type-I was unusual in the sense that the frequencies of the Raman lines associated primarily with methine-bridge CC-stretching vibrations were relatively high in comparison with those of other high spin hemoproteins. Type-I was converted directly to Type-III upon the addition of SDS or 2-propanol but the conversion occurred via Type-II when pH was increased. Structural difference between the high spin hemes of Type-I and Type-II was discussed in detail."}
{"id": "PMID:20978", "title": "Hydrogen ion titration and amino acid analysis of hemocyanin from the spiny lobster Jasus edwardsii.", "content": "Potentiometric and spectrophotometric titrations, isoelectric focusing and amino acid analyses, have been made on the hemocyanin from Jasus edwardsii. Counts of acidic neutral and alkaline groups were made from the titrations, enabling comparisons to be made with the amino acid analysis. Thermodynamic analysis of the data indicated that changes in the native protein structure took place at pH 4.0, 8.4 and 10.7. These observations are discussed in terms of dissociation, shifts in pK and conformational changes in the protein.", "contents": "Hydrogen ion titration and amino acid analysis of hemocyanin from the spiny lobster Jasus edwardsii. Potentiometric and spectrophotometric titrations, isoelectric focusing and amino acid analyses, have been made on the hemocyanin from Jasus edwardsii. Counts of acidic neutral and alkaline groups were made from the titrations, enabling comparisons to be made with the amino acid analysis. Thermodynamic analysis of the data indicated that changes in the native protein structure took place at pH 4.0, 8.4 and 10.7. These observations are discussed in terms of dissociation, shifts in pK and conformational changes in the protein."}
{"id": "PMID:20979", "title": "Effect of tyrosine ionization upon biological activities of angiotensin II and two new peptide analogues.", "content": "The role of the tyrosine side-chain in the smooth muscle contracting activity of angiotensin III was investigated by determining intrinsic activities and ED50 values of [4-(3-chlorotyrosine)]angiotensin II and [4-(3-benzyltyrosine)]angiotensin II in the isolated guinea-pig ileum and rat uterus. [4-(3-chlorotyrosine)]angiotensin II activity was compared with that of angiotensin II at different pH values, in which the ratio of their degrees of phenolic ionization varied. The results indicated that deprotonation of the phenolic group hinders binding to smooth muscle cell receptors, but not triggering of the response by the hormone-receptor complex. Steric hindrance by the benzyl substituent in [4-(3-benzyltyrosine)]angiotensin II reduced both receptor-binding and triggering of the response.", "contents": "Effect of tyrosine ionization upon biological activities of angiotensin II and two new peptide analogues. The role of the tyrosine side-chain in the smooth muscle contracting activity of angiotensin III was investigated by determining intrinsic activities and ED50 values of [4-(3-chlorotyrosine)]angiotensin II and [4-(3-benzyltyrosine)]angiotensin II in the isolated guinea-pig ileum and rat uterus. [4-(3-chlorotyrosine)]angiotensin II activity was compared with that of angiotensin II at different pH values, in which the ratio of their degrees of phenolic ionization varied. The results indicated that deprotonation of the phenolic group hinders binding to smooth muscle cell receptors, but not triggering of the response by the hormone-receptor complex. Steric hindrance by the benzyl substituent in [4-(3-benzyltyrosine)]angiotensin II reduced both receptor-binding and triggering of the response."}
{"id": "PMID:20980", "title": "Increased oxygen affinity for hemoglobin Sawara: alphaA4(6) aspartic acid replaced by alanine.", "content": "The oxygen binding property of Hb Sawara (alphaA4 Asp replaced by Ala) was studied at different pH values with and without addition of 2,3-diphosphoglycerate. The oxygen affinity of Hb Sawara was shown to be increased, the difference of the log P50 value between normal and abnormal hemoglobins being 0.37 at pH 7.0. Both the magnitude of the alkaline Bohr effect and the effect of 2,3-diphosphoglycerate upon oxygen affinity of Hb Sawara were comparable to those of Hb A. The amino acid substitution of alanine for alphaA4 aspartic acid might result in the loss of a stabilizing force for ionic interaction between the alpha-amino group of NA (1)alpha1 valine and the alpha-carboxyl of HC3(141)alpha2 arginine in the deoxy-form.", "contents": "Increased oxygen affinity for hemoglobin Sawara: alphaA4(6) aspartic acid replaced by alanine. The oxygen binding property of Hb Sawara (alphaA4 Asp replaced by Ala) was studied at different pH values with and without addition of 2,3-diphosphoglycerate. The oxygen affinity of Hb Sawara was shown to be increased, the difference of the log P50 value between normal and abnormal hemoglobins being 0.37 at pH 7.0. Both the magnitude of the alkaline Bohr effect and the effect of 2,3-diphosphoglycerate upon oxygen affinity of Hb Sawara were comparable to those of Hb A. The amino acid substitution of alanine for alphaA4 aspartic acid might result in the loss of a stabilizing force for ionic interaction between the alpha-amino group of NA (1)alpha1 valine and the alpha-carboxyl of HC3(141)alpha2 arginine in the deoxy-form."}
{"id": "PMID:20982", "title": "Thermodynamic study of the formation of adenine nucleotide-manganese complexes. I. \"pH stat\" titration method results.", "content": "The thermodynamics associated with the Mn2- -ATP, Mn-ADP- and Mn-AMP complex formation reactions determined from K potentiometric measurements at I = 0.2 are reported for the temperature range 1--45 degrees C. The K values increase with the length of the phosphate chain and with temperature. The limits and the best conditions for use of the \"pH stat\" titration method are discussed. Comparison with the results obtained by potentiometric and calorimetric methods in the case of Mg-nucleotide complexes is made.", "contents": "Thermodynamic study of the formation of adenine nucleotide-manganese complexes. I. \"pH stat\" titration method results. The thermodynamics associated with the Mn2- -ATP, Mn-ADP- and Mn-AMP complex formation reactions determined from K potentiometric measurements at I = 0.2 are reported for the temperature range 1--45 degrees C. The K values increase with the length of the phosphate chain and with temperature. The limits and the best conditions for use of the \"pH stat\" titration method are discussed. Comparison with the results obtained by potentiometric and calorimetric methods in the case of Mg-nucleotide complexes is made."}
{"id": "PMID:20983", "title": "Thermodynamic study of the formation of adenine nucleotide-manganese complexes. II. Calorimetric results.", "content": "Enthalpic variations in the formation of adenine nucleotide-manganese complexes, as measured by microcalorimetry, are reported. All the results are obtained in the temperature range 6--30 degrees C at I =0.2 and pH values 7.00 or 7.50. All the reactions are endothermic and the deltaH values increase with the length of the phosphate chain and with temperature. The deltaH values are compared with those previously obtained for adenine nucleotide-manganesium complexes. The comparison between calorimetric and potentiometric deltaH values is made. The divergence observed between these results at low temperature leads us to assume the formation of nucleotide aggregates induced by the presence of manganese ions. This hypothesis is confirmed by differential ultraviolet spectra.", "contents": "Thermodynamic study of the formation of adenine nucleotide-manganese complexes. II. Calorimetric results. Enthalpic variations in the formation of adenine nucleotide-manganese complexes, as measured by microcalorimetry, are reported. All the results are obtained in the temperature range 6--30 degrees C at I =0.2 and pH values 7.00 or 7.50. All the reactions are endothermic and the deltaH values increase with the length of the phosphate chain and with temperature. The deltaH values are compared with those previously obtained for adenine nucleotide-manganesium complexes. The comparison between calorimetric and potentiometric deltaH values is made. The divergence observed between these results at low temperature leads us to assume the formation of nucleotide aggregates induced by the presence of manganese ions. This hypothesis is confirmed by differential ultraviolet spectra."}
{"id": "PMID:20988", "title": "[Isolation and characterization of beta-D-galactosidase from gastric juice].", "content": "A method for beta-D-galactosidase isolation from cattle gastric juice has been developed. Gastric juice mucus was removed by and addition of equimolar amounts of Na2HPO4 and CaCl2. The removal of proteases and other proteins was achieved by the treatment with resins KB-51X2 and AN-22. The resulting preparation had specific activity of 0.14 units per mg of protein. Gel filtration on Sepharose 4B led to an increase of specific activity of the preparation up to 0,4 units per mg of protein. Some properties of the beta-D-galactosidase obtained were compared to relation of lactose and o-nitrophenyl-beta-D-galactoside (pH optima, temperature optimym and thermostability).", "contents": "[Isolation and characterization of beta-D-galactosidase from gastric juice]. A method for beta-D-galactosidase isolation from cattle gastric juice has been developed. Gastric juice mucus was removed by and addition of equimolar amounts of Na2HPO4 and CaCl2. The removal of proteases and other proteins was achieved by the treatment with resins KB-51X2 and AN-22. The resulting preparation had specific activity of 0.14 units per mg of protein. Gel filtration on Sepharose 4B led to an increase of specific activity of the preparation up to 0,4 units per mg of protein. Some properties of the beta-D-galactosidase obtained were compared to relation of lactose and o-nitrophenyl-beta-D-galactoside (pH optima, temperature optimym and thermostability)."}
{"id": "PMID:20989", "title": "[Kinetic study of o-dianisidine oxidation by hydrogen peroxide in the presence of horseradish peroxidase].", "content": "A kinetic study of o-dianisidine oxidation by hydrogen peroxide in the presence of horseradish peroxidase within the pH range of 3.7-9.0 has been carried out. It was shown that the reaction of o-dianisidine peroxidase oxidation obeys the Michaelis--Menten kinetics; the kcat and Km values within the pH range used were determined. The optimum of peroxidase catalytic activity during o-dianisidine oxidation was observed at pH 5.0-6.0. The kinetic pattern of the reaction is discussed. It was demonstrated that deprotonation of the group at pK 6.5 decreases the kcat value 60 times. At pH greater than 8.0 an additional ionogenic group controls the enzyme activity.", "contents": "[Kinetic study of o-dianisidine oxidation by hydrogen peroxide in the presence of horseradish peroxidase]. A kinetic study of o-dianisidine oxidation by hydrogen peroxide in the presence of horseradish peroxidase within the pH range of 3.7-9.0 has been carried out. It was shown that the reaction of o-dianisidine peroxidase oxidation obeys the Michaelis--Menten kinetics; the kcat and Km values within the pH range used were determined. The optimum of peroxidase catalytic activity during o-dianisidine oxidation was observed at pH 5.0-6.0. The kinetic pattern of the reaction is discussed. It was demonstrated that deprotonation of the group at pK 6.5 decreases the kcat value 60 times. At pH greater than 8.0 an additional ionogenic group controls the enzyme activity."}
{"id": "PMID:20990", "title": "[Purification and some properties of isozymes 1 and 5 of lactate dehydrogenase from fox heart and skeletal muscles].", "content": "An improved method  is described for the isolation of isozymes 1 and 5 of lactate dehydrogenase (LDH) from heart and skeletal muscles of foxes. The method includes salt fractionation with ammonium sulphate, chromatography on DEAE- and CM-celluloses and affinity chromatography on AMP-Sepharose. The preparations of LDH isozymes 1 and 5 turned out to be homogeneous both in 7,5% polyacrylamide gel electrophoresis and under immunodiffusion analysis. It is shown that the pH optimum for LDH-1 is 10.2-10.4 for LDH-5 it is 9.5-9.6 in the case of the direct reaction, and the pH optimum is 7.6-7.8 for LDH-1 and 7.3-7.4 for LDH-5 in the case of reverse reaction. The values of Mikhaelis constants were determined for substrates and coenzymes in direct and reverse reactions. It is found that the excess of lactate and pyruvate causes substrate inhibition of both LDH-1 and LDH-5. The activities of LDH-1 and LDH-5 showed an unexpected similar sensitivity to the inhibitory effect of high pyruvate concentrations.", "contents": "[Purification and some properties of isozymes 1 and 5 of lactate dehydrogenase from fox heart and skeletal muscles]. An improved method  is described for the isolation of isozymes 1 and 5 of lactate dehydrogenase (LDH) from heart and skeletal muscles of foxes. The method includes salt fractionation with ammonium sulphate, chromatography on DEAE- and CM-celluloses and affinity chromatography on AMP-Sepharose. The preparations of LDH isozymes 1 and 5 turned out to be homogeneous both in 7,5% polyacrylamide gel electrophoresis and under immunodiffusion analysis. It is shown that the pH optimum for LDH-1 is 10.2-10.4 for LDH-5 it is 9.5-9.6 in the case of the direct reaction, and the pH optimum is 7.6-7.8 for LDH-1 and 7.3-7.4 for LDH-5 in the case of reverse reaction. The values of Mikhaelis constants were determined for substrates and coenzymes in direct and reverse reactions. It is found that the excess of lactate and pyruvate causes substrate inhibition of both LDH-1 and LDH-5. The activities of LDH-1 and LDH-5 showed an unexpected similar sensitivity to the inhibitory effect of high pyruvate concentrations."}
{"id": "PMID:20986", "title": "[Photogeneration of a 2-vector transmembrane proton gradient in Halobacterium halobium R1 cells].", "content": "Analysing 4 phases of light-dependent change of pH in cell suspension of H. halobium R1 it has been found that an increase of pH I when light is switched on and a decrease of pH II during further illumination are proportional to the light effect and are energy-dependent. Neutralization of these changes (phases III and IV) proceeds spontaneously in the darkness. These data show that the transmembrane gradient of protons is generated in two directions--delta pH and +delta pH, simultaneous presence of which points to the local character of one of them. Generation of -delta pH associated with light energy utilization by the cells is considered as a result of neutralization of the negative charge and +delta pH1 (latent), appearing due to a change in bacteriorodopsin conformation under illumination. It may be also suggested that the yield of protons from the cells of pHII and generation of +delta pH result from the discoupling of photoprocesses and energy utilization by the cells, containing bacteriorodopsin.", "contents": "[Photogeneration of a 2-vector transmembrane proton gradient in Halobacterium halobium R1 cells]. Analysing 4 phases of light-dependent change of pH in cell suspension of H. halobium R1 it has been found that an increase of pH I when light is switched on and a decrease of pH II during further illumination are proportional to the light effect and are energy-dependent. Neutralization of these changes (phases III and IV) proceeds spontaneously in the darkness. These data show that the transmembrane gradient of protons is generated in two directions--delta pH and +delta pH, simultaneous presence of which points to the local character of one of them. Generation of -delta pH associated with light energy utilization by the cells is considered as a result of neutralization of the negative charge and +delta pH1 (latent), appearing due to a change in bacteriorodopsin conformation under illumination. It may be also suggested that the yield of protons from the cells of pHII and generation of +delta pH result from the discoupling of photoprocesses and energy utilization by the cells, containing bacteriorodopsin."}
{"id": "PMID:20991", "title": "[Comparative study of NADP-reductase properties in two species of purple bacteria].", "content": "Unlike Rhodospirillum rubrum, the highly purified preparations of NADP-reductase Thiocapsa roseopersicina are capable of reduction of cytochrome c though they do not catalyse diaphorase reaction in the presence of methyl viologen or benzyl viologen and NADH. T. roseopersicina reductase has more high temperature optimum (50-65 degrees) and more high thermal stability (65 degrees) and it is capable to catalyse diaphorase and menadione-reductase reactions under more high pH values (11.0-12.0) than NADP-reductase of R. rubrum. NADP-reductase of T. roseopersicina is more stable under storing than the enzyme from R. rubrum: the semi-inactivation period of the enzyme when storing in Ar or the air is about 10 and 4 days, respectively, and it takes about three days for R. rubrum.", "contents": "[Comparative study of NADP-reductase properties in two species of purple bacteria]. Unlike Rhodospirillum rubrum, the highly purified preparations of NADP-reductase Thiocapsa roseopersicina are capable of reduction of cytochrome c though they do not catalyse diaphorase reaction in the presence of methyl viologen or benzyl viologen and NADH. T. roseopersicina reductase has more high temperature optimum (50-65 degrees) and more high thermal stability (65 degrees) and it is capable to catalyse diaphorase and menadione-reductase reactions under more high pH values (11.0-12.0) than NADP-reductase of R. rubrum. NADP-reductase of T. roseopersicina is more stable under storing than the enzyme from R. rubrum: the semi-inactivation period of the enzyme when storing in Ar or the air is about 10 and 4 days, respectively, and it takes about three days for R. rubrum."}
{"id": "PMID:20987", "title": "[Functional role of parvalbumins in regulating Ca2+ in the contraction--relaxation cycle of vertebrate skeletal muscles].", "content": "On the basis of parvalbumin property to change Ca2+-binding constant within the pH-region from approxim-tely 7 to approximately 8 a hypothesis that parvalbumins are pH-regulated Ca2+-depot in muscles has been stated. The addition of parvalbumin to native actomysin complex at pH approximately 7 in the presence of ATP and Ca2+ results in partial inhibition of its superprecipitation. The change of pH up to approximately 8 leads to the restoration of actomyosin superprecipitation.", "contents": "[Functional role of parvalbumins in regulating Ca2+ in the contraction--relaxation cycle of vertebrate skeletal muscles]. On the basis of parvalbumin property to change Ca2+-binding constant within the pH-region from approxim-tely 7 to approximately 8 a hypothesis that parvalbumins are pH-regulated Ca2+-depot in muscles has been stated. The addition of parvalbumin to native actomysin complex at pH approximately 7 in the presence of ATP and Ca2+ results in partial inhibition of its superprecipitation. The change of pH up to approximately 8 leads to the restoration of actomyosin superprecipitation."}
{"id": "PMID:20992", "title": "[Virioimmunoassay for studying the interaction of diphtheria toxin with cell membranes].", "content": "A model for studying the interaction of diphtheria toxin with cell membranes includes immobilization of purified cell membranes on Sephadex G-25, adsorbtion of toxin on the membranes in the presence of protective colloid, and subsequent detection of adsorbed toxin by means of virioimmunoassay. Diphtheria toxin adsorbed rapidly on membranes of both sensitive (HeLa, macrophages) and resistent to tis action cells, but not on stromaof human erythrocytes. The rate of interaction depends on the concentration of toxin and the temperature of incubation. Adsorbed toxin may be eluted by acidic buffer, 8 M area and 4 M guanidin. HCl, but not by triton X-100, tween 20 and 80, sodium dodecylaulfate and basic buffer.", "contents": "[Virioimmunoassay for studying the interaction of diphtheria toxin with cell membranes]. A model for studying the interaction of diphtheria toxin with cell membranes includes immobilization of purified cell membranes on Sephadex G-25, adsorbtion of toxin on the membranes in the presence of protective colloid, and subsequent detection of adsorbed toxin by means of virioimmunoassay. Diphtheria toxin adsorbed rapidly on membranes of both sensitive (HeLa, macrophages) and resistent to tis action cells, but not on stromaof human erythrocytes. The rate of interaction depends on the concentration of toxin and the temperature of incubation. Adsorbed toxin may be eluted by acidic buffer, 8 M area and 4 M guanidin. HCl, but not by triton X-100, tween 20 and 80, sodium dodecylaulfate and basic buffer."}
{"id": "PMID:20993", "title": "[Precipitation of neutral alpha-glucans and separation of mixtures by dimethyldodecylbenzylammonium chloride].", "content": "The solubilization of precipitated complex of alpha-polyglucane-dimethyldodecylbenzylammonium chloride in excess of a solution of the salt was found to be dependent on pH. The complexes of glycogen having a more branching structure are dissolved much more readily than the amylopectin complexes. The conditions for separation of mixtures of these two alpha-glucanes were found. The purity of glycogen and amylopectin obtained after separation from the mixture was established both by comparing the absorption spectra of their iodinepolysaccharide complexes and by separation of radioactive amylopectin and non-radioactive glycogen mixture.", "contents": "[Precipitation of neutral alpha-glucans and separation of mixtures by dimethyldodecylbenzylammonium chloride]. The solubilization of precipitated complex of alpha-polyglucane-dimethyldodecylbenzylammonium chloride in excess of a solution of the salt was found to be dependent on pH. The complexes of glycogen having a more branching structure are dissolved much more readily than the amylopectin complexes. The conditions for separation of mixtures of these two alpha-glucanes were found. The purity of glycogen and amylopectin obtained after separation from the mixture was established both by comparing the absorption spectra of their iodinepolysaccharide complexes and by separation of radioactive amylopectin and non-radioactive glycogen mixture."}
{"id": "PMID:20994", "title": "[Regulation of Na, K-ATPase activity by monovalent cations].", "content": "A deviation from optimal conditions of the Na, K-ATPase reaction results in a drastic change in the plot: enzyme activity versus Na/K ratio. Acidification of the medium and a decrease in Mg2+ concentration and temperature results in two peaks on the curve at Na/K ratio of about 1 and at Na/K ratio greater than 4. The enhancement of pH of the medium and increase in Mg2+ concentration decreases the first peak and increases the second one. A comparison of these curves for hydrolysis of ATP, UTP and p-nitrophenylphosphate and temperature dependence of the hydrolysis of the substrates suggest that the anomalies observed may be accounted for the Na+ effect on the K-sites or K+ effect on the Na-sites under conditions when cation-binding sites are heterogeneous.", "contents": "[Regulation of Na, K-ATPase activity by monovalent cations]. A deviation from optimal conditions of the Na, K-ATPase reaction results in a drastic change in the plot: enzyme activity versus Na/K ratio. Acidification of the medium and a decrease in Mg2+ concentration and temperature results in two peaks on the curve at Na/K ratio of about 1 and at Na/K ratio greater than 4. The enhancement of pH of the medium and increase in Mg2+ concentration decreases the first peak and increases the second one. A comparison of these curves for hydrolysis of ATP, UTP and p-nitrophenylphosphate and temperature dependence of the hydrolysis of the substrates suggest that the anomalies observed may be accounted for the Na+ effect on the K-sites or K+ effect on the Na-sites under conditions when cation-binding sites are heterogeneous."}
{"id": "PMID:20995", "title": "[Reversible dissociation of malate dehydrogenase from plants].", "content": "It was demonstrated that 0.2 M citric acid (pH 2.5) inactivates highly-purified malate dehydrogenase from tea leaves; the degree of inactivation depends on temperature and time of incubation. The enzyme activity is restored by certain inorganic salts, the degree of reactivation being dependent on pH, ionic strengths of salts and duration of enzyme incubation with both inactivating and reactivating agents. Urea and guanidine hydrochloride also have a reversibly inactivating effect on the enzyme. The degree of inactivation depends on their concentration and incubation time. In the latter case reactivation of enzyme is achieved by dialysis or 20-40-fold dilution of the enzyme preparation. A kinetic study demonstrated that inactivation of enzyme by the above-mentioned agents is due to the enzyme dissociation into 4 catalytically inactive subunits with molecular weights of 17 500 +/- 1000, which under certain conditions are capable of reassociating into an active molecule of enzyme with completely restored native conformation.", "contents": "[Reversible dissociation of malate dehydrogenase from plants]. It was demonstrated that 0.2 M citric acid (pH 2.5) inactivates highly-purified malate dehydrogenase from tea leaves; the degree of inactivation depends on temperature and time of incubation. The enzyme activity is restored by certain inorganic salts, the degree of reactivation being dependent on pH, ionic strengths of salts and duration of enzyme incubation with both inactivating and reactivating agents. Urea and guanidine hydrochloride also have a reversibly inactivating effect on the enzyme. The degree of inactivation depends on their concentration and incubation time. In the latter case reactivation of enzyme is achieved by dialysis or 20-40-fold dilution of the enzyme preparation. A kinetic study demonstrated that inactivation of enzyme by the above-mentioned agents is due to the enzyme dissociation into 4 catalytically inactive subunits with molecular weights of 17 500 +/- 1000, which under certain conditions are capable of reassociating into an active molecule of enzyme with completely restored native conformation."}
{"id": "PMID:20996", "title": "[Effects of nucleophils on kinetic parameters of peroxidase-catalyzed oxidative reactions].", "content": "The effect of imidazole on the kinetic parameters of reactions of potassium ferrocyanide and o-dianizidine peroxidation by hydrogen peroxide within a wide range of pH was studied. It was shown that imidazole activates the reaction of o-dianizidine peroxidation at pH greater than or equal to 6.5, but does not affect the oxidation of potassium ferrocyanide. It was also found that imidazole causes a similar increase in the kkat and Km, i. e. non-competitive activation occurs. The data obtained suggest a possible mechanism of the activator effect. Differences in the mechanism of interaction of various substrates uith peroxidase are discussed.", "contents": "[Effects of nucleophils on kinetic parameters of peroxidase-catalyzed oxidative reactions]. The effect of imidazole on the kinetic parameters of reactions of potassium ferrocyanide and o-dianizidine peroxidation by hydrogen peroxide within a wide range of pH was studied. It was shown that imidazole activates the reaction of o-dianizidine peroxidation at pH greater than or equal to 6.5, but does not affect the oxidation of potassium ferrocyanide. It was also found that imidazole causes a similar increase in the kkat and Km, i. e. non-competitive activation occurs. The data obtained suggest a possible mechanism of the activator effect. Differences in the mechanism of interaction of various substrates uith peroxidase are discussed."}
{"id": "PMID:20997", "title": "[Dependence of thrombin- and trypsin-catalyzed hydrolysis of N-alpha-arylsulfonyl-L-arginine methyl esters on the structure of acylamide part of substrates].", "content": "For comparative studies on the esterase activities of thrombin and trypsin N(alpha)-arylsulfonyl-L-arginine methyl esters were synthetised containing in aromatic ring substituents of different polar nature, size and hydrophobicity. The kinetics of their hydrolysis by thrombin and trypsin were measured. Values of Km and kcat in steady-state conditions were determined. It was shown, that thrombin-catalysed hydrolysis was more sensitive than that of trypsin to the nature of substituents of arylsulfonyl group and determined by their polar and steric effects. A line correlation between specificity constants (kcat/Km) and sigma and Es of substituents were demonstrated. The difference in reactivity of compounds under investigation is suggested to depend on alterations of stability of hydrogen bond between arylsulfonylamide nitrogen atom of substrate and the active center of the enzyme due to changes in the acidity of the arylsulfonylamide group affected by substituent of the benzene ring.", "contents": "[Dependence of thrombin- and trypsin-catalyzed hydrolysis of N-alpha-arylsulfonyl-L-arginine methyl esters on the structure of acylamide part of substrates]. For comparative studies on the esterase activities of thrombin and trypsin N(alpha)-arylsulfonyl-L-arginine methyl esters were synthetised containing in aromatic ring substituents of different polar nature, size and hydrophobicity. The kinetics of their hydrolysis by thrombin and trypsin were measured. Values of Km and kcat in steady-state conditions were determined. It was shown, that thrombin-catalysed hydrolysis was more sensitive than that of trypsin to the nature of substituents of arylsulfonyl group and determined by their polar and steric effects. A line correlation between specificity constants (kcat/Km) and sigma and Es of substituents were demonstrated. The difference in reactivity of compounds under investigation is suggested to depend on alterations of stability of hydrogen bond between arylsulfonylamide nitrogen atom of substrate and the active center of the enzyme due to changes in the acidity of the arylsulfonylamide group affected by substituent of the benzene ring."}
{"id": "PMID:20998", "title": "[Characterization of dextranase from Penicillium purpurogenum (Ftoll)].", "content": "An extracellular dextranase (E. C. 3.2.1.11) was purified from cell-free culture filtrates of Penicillium purpurogenum (Ftoll). The enzyme was most active at pH 5,5. The dextranase was endo-type, it split quickly isomaltotetraose into two isomaltose molecules, slowly degraded isomaltotriose, and did not act on isomaltose. The rate of isomaltooligosaccharides hydrolysis was increased with the increase of the polymerization degree. Polyols obtained from isomaltooligosaccharides were split more slowly than the respective sugars. The isomaltopentaitol was split at two glucosidic linkages, 38% of hydrolyzed linkages being the second linkage from the sorbitol end of the molecule and 62% being the third one. The degree of degradation of dextrans depended on amount of 1,6 linkages. Isomaltose and tetrasaccharides of two types, 2(2)-alpha-D-glucosylmaltotriose and linear tetrasaccharide(s), are the lowest molecular weight products of exhaustive hydrolysis of branched dextrans.", "contents": "[Characterization of dextranase from Penicillium purpurogenum (Ftoll)]. An extracellular dextranase (E. C. 3.2.1.11) was purified from cell-free culture filtrates of Penicillium purpurogenum (Ftoll). The enzyme was most active at pH 5,5. The dextranase was endo-type, it split quickly isomaltotetraose into two isomaltose molecules, slowly degraded isomaltotriose, and did not act on isomaltose. The rate of isomaltooligosaccharides hydrolysis was increased with the increase of the polymerization degree. Polyols obtained from isomaltooligosaccharides were split more slowly than the respective sugars. The isomaltopentaitol was split at two glucosidic linkages, 38% of hydrolyzed linkages being the second linkage from the sorbitol end of the molecule and 62% being the third one. The degree of degradation of dextrans depended on amount of 1,6 linkages. Isomaltose and tetrasaccharides of two types, 2(2)-alpha-D-glucosylmaltotriose and linear tetrasaccharide(s), are the lowest molecular weight products of exhaustive hydrolysis of branched dextrans."}
{"id": "PMID:20999", "title": "[Effect of environment on allosteric properties of acetylcholinesterase].", "content": "In the presence of organophosphorus inhibitors (OPI) AChE inhibition is initiated at a lower concentration of ACh; the plot reaction rate versus substrate concentration shows two maxima with a distinct minimum between them. It was shown that extremely mild conditions (short-term heating up to 50 degrees C; acidic or alkaline pH shift by 0.5 units; high concentrations of bivalent cations; erythrocyte storage) which do not affect substrate inhibition, remove this effect. The data obtained suggest that OPI effect is not directed to the site of AChE responsible for enzyme inhibition by ACh excess (\"substrate inhibition site\"), but to some other area. This results in a change in the conformation of the substrate inhibition site and a pronounced inhibition of the AChE activity takes place at lower substrate concentration.", "contents": "[Effect of environment on allosteric properties of acetylcholinesterase]. In the presence of organophosphorus inhibitors (OPI) AChE inhibition is initiated at a lower concentration of ACh; the plot reaction rate versus substrate concentration shows two maxima with a distinct minimum between them. It was shown that extremely mild conditions (short-term heating up to 50 degrees C; acidic or alkaline pH shift by 0.5 units; high concentrations of bivalent cations; erythrocyte storage) which do not affect substrate inhibition, remove this effect. The data obtained suggest that OPI effect is not directed to the site of AChE responsible for enzyme inhibition by ACh excess (\"substrate inhibition site\"), but to some other area. This results in a change in the conformation of the substrate inhibition site and a pronounced inhibition of the AChE activity takes place at lower substrate concentration."}
{"id": "PMID:21000", "title": "[Proteins of Bacillus thuringiensis delta-endotoxin crystals].", "content": "Pure crystals (at least 99% purification) of sigma-endotoxin were isolated from Bac. thuringiensis var. galleriae. The complete dissolution of crystals might be achieved by the increase of pH up to 12 and higher or by a combined action of S = S-reducing and denaturing agents. Electrophoresis of the solubilized crystal proteins in 5% polyacrylamide gels containing 0,1% sodium dodecyl sulfate and 8 M urea reveals two major bands corresponding to molecular weights of 120000--140000 (65%) and 65000 (8-10%), and some minor components whose molecular weights varied from 65000 to 340000. Urea (3--8 M) causes to partial dissolution of the crystals; the component with molecular weight of 65000 is mainly found in the solution (component A). In dithioerythritol extracts at pH 9 the major component of the crystal is the protein with molecular weight 120000--140000 (component B). The crystals, alkali-soluble components and proteins isolated from crystals by selective extraction (3--8 M urea or 0.01 M dithioerythrytol, pH 9) were found toxic for the larvae of Galleria mellonella.", "contents": "[Proteins of Bacillus thuringiensis delta-endotoxin crystals]. Pure crystals (at least 99% purification) of sigma-endotoxin were isolated from Bac. thuringiensis var. galleriae. The complete dissolution of crystals might be achieved by the increase of pH up to 12 and higher or by a combined action of S = S-reducing and denaturing agents. Electrophoresis of the solubilized crystal proteins in 5% polyacrylamide gels containing 0,1% sodium dodecyl sulfate and 8 M urea reveals two major bands corresponding to molecular weights of 120000--140000 (65%) and 65000 (8-10%), and some minor components whose molecular weights varied from 65000 to 340000. Urea (3--8 M) causes to partial dissolution of the crystals; the component with molecular weight of 65000 is mainly found in the solution (component A). In dithioerythritol extracts at pH 9 the major component of the crystal is the protein with molecular weight 120000--140000 (component B). The crystals, alkali-soluble components and proteins isolated from crystals by selective extraction (3--8 M urea or 0.01 M dithioerythrytol, pH 9) were found toxic for the larvae of Galleria mellonella."}
{"id": "PMID:21004", "title": "The gas chromatography mass spectrometry of the major metabolites of flurazepam.", "content": "Mass spectra and gas chromatographic data are presented for flurazepam and its metabolites; monodesethylflurazepam, didesethylflurazepam, hydroxyethylflurazepam, N1-desalkylflurazepam, N1-desalkyl-3-hydroxy-flurazepam, and flurazepam-N1-acetic acid. The on-column thermal degradation of didesethylflurazepam, N1-desalkyl-3-hydroxyflurazepam and flurazepam-N1-acetic acid is reported and discussed. Mass spectrometric and gas chromatographic data are also presented for the benzophenones obtained by acid hydrolysis of flurazepam and its metabolites. The occurrence of flurazepam metabolites in urine from five forensic cases after various treatments has been investigated. A possible new 'metabolite' of flurazepam was detected in two of these cases.", "contents": "The gas chromatography mass spectrometry of the major metabolites of flurazepam. Mass spectra and gas chromatographic data are presented for flurazepam and its metabolites; monodesethylflurazepam, didesethylflurazepam, hydroxyethylflurazepam, N1-desalkylflurazepam, N1-desalkyl-3-hydroxy-flurazepam, and flurazepam-N1-acetic acid. The on-column thermal degradation of didesethylflurazepam, N1-desalkyl-3-hydroxyflurazepam and flurazepam-N1-acetic acid is reported and discussed. Mass spectrometric and gas chromatographic data are also presented for the benzophenones obtained by acid hydrolysis of flurazepam and its metabolites. The occurrence of flurazepam metabolites in urine from five forensic cases after various treatments has been investigated. A possible new 'metabolite' of flurazepam was detected in two of these cases."}
{"id": "PMID:21006", "title": "[Changes in the electrical activity of myocardial fibers following heart transplantation to under the skin of the ear in mice].", "content": "Intracellular rest and action potentials (RP and AP, respectively) of mouse heart graft were reduced on the 3rd--4th days after the transplantation as compared with the intracellular potentials of newborn mice. Beginning from the 5th--6th days there occurred a gradual increase of the intracellular potentials of amplitude. The firt 7--8 days, both in the case of allograft and heterograft, the changes in the intracellular activity were the same. Then in heterograft there occurred a repeated reduction of the RP and AP amplitude of the graft myocardial fibers, this apparently being connected with the development of the rejection reaction. In the allograft samples the amplitude of the intracellular potentials approached by the end of the first month after the graft with RP and AP values of the recipient's myocardial fibers.", "contents": "[Changes in the electrical activity of myocardial fibers following heart transplantation to under the skin of the ear in mice]. Intracellular rest and action potentials (RP and AP, respectively) of mouse heart graft were reduced on the 3rd--4th days after the transplantation as compared with the intracellular potentials of newborn mice. Beginning from the 5th--6th days there occurred a gradual increase of the intracellular potentials of amplitude. The firt 7--8 days, both in the case of allograft and heterograft, the changes in the intracellular activity were the same. Then in heterograft there occurred a repeated reduction of the RP and AP amplitude of the graft myocardial fibers, this apparently being connected with the development of the rejection reaction. In the allograft samples the amplitude of the intracellular potentials approached by the end of the first month after the graft with RP and AP values of the recipient's myocardial fibers."}
{"id": "PMID:21007", "title": "[Inhibitory processes in the cerebral cortex and the anticonvulsive action of benzodiazepine derivatives].", "content": "A comparative study of the effect of some benzodiazepine deprivatives (chlonazepam, lorazepam, diazepam, and medazepam) on the recovery cycles of the interzonal response was carried out on unanesthetized curare-immobilized cats. These drugs proved to selectively inhibit the testing potential within the range of 20 to 100 msec. between the conditioning and the testing stimuli. This indicates that potentiation of GABA-ergic inhibition in the cerebral cortex. The threshold doses of the drugs inducing the depression of the test response and of ED50, preventing the development of convulsions, caused by GABA deficiency or by GABA-ergic receptor block, were compared; a correlation between the mentioned effects was demonstrated. The significance of GABA-positive effect of benzodiazepines in the mechanism of their anticonvulsive activity is suggested.", "contents": "[Inhibitory processes in the cerebral cortex and the anticonvulsive action of benzodiazepine derivatives]. A comparative study of the effect of some benzodiazepine deprivatives (chlonazepam, lorazepam, diazepam, and medazepam) on the recovery cycles of the interzonal response was carried out on unanesthetized curare-immobilized cats. These drugs proved to selectively inhibit the testing potential within the range of 20 to 100 msec. between the conditioning and the testing stimuli. This indicates that potentiation of GABA-ergic inhibition in the cerebral cortex. The threshold doses of the drugs inducing the depression of the test response and of ED50, preventing the development of convulsions, caused by GABA deficiency or by GABA-ergic receptor block, were compared; a correlation between the mentioned effects was demonstrated. The significance of GABA-positive effect of benzodiazepines in the mechanism of their anticonvulsive activity is suggested."}
{"id": "PMID:21008", "title": "[Changes in the H-alloantigen-recognizing function of mouse lymphoid cells following hydrocortisone administration].", "content": "The capacity of spleen, thymus, and bone marrow cells of intact (control) and of hydrocortisone-treated mice CBA to induce the lymph node type of graft-v-host reaction (GVHR) in hybrids F1 (CBA X c57bl) was studied. After hydrocortisone injection (2.5 mg per mouse) the donor spleen cells became more active in GVHR, considering the value of lymph node indices and immunoblast content in the regional lymph node as compared with a control group. Following transplantation of thymus cells taken from the hydrocortison-treated donors the immunoblast count was higher, although the lymph node weight remained the same as in the control group. On the contrary, following the transfer of the bone marrow cells from the hydrocortisone-treated mice the lymph nodes enlarged, while the immunoblast count remained as low as in control. Consequently, exogenously conditioned increase in the hydrocortisone level was accompanied by an enrichment of the spleen and thymus cell populations with T-lymphocytes, proliferating in response to H-alloantigens.", "contents": "[Changes in the H-alloantigen-recognizing function of mouse lymphoid cells following hydrocortisone administration]. The capacity of spleen, thymus, and bone marrow cells of intact (control) and of hydrocortisone-treated mice CBA to induce the lymph node type of graft-v-host reaction (GVHR) in hybrids F1 (CBA X c57bl) was studied. After hydrocortisone injection (2.5 mg per mouse) the donor spleen cells became more active in GVHR, considering the value of lymph node indices and immunoblast content in the regional lymph node as compared with a control group. Following transplantation of thymus cells taken from the hydrocortison-treated donors the immunoblast count was higher, although the lymph node weight remained the same as in the control group. On the contrary, following the transfer of the bone marrow cells from the hydrocortisone-treated mice the lymph nodes enlarged, while the immunoblast count remained as low as in control. Consequently, exogenously conditioned increase in the hydrocortisone level was accompanied by an enrichment of the spleen and thymus cell populations with T-lymphocytes, proliferating in response to H-alloantigens."}
{"id": "PMID:21009", "title": "[Effect of aminazin on the enzymatic oxidation of lipids].", "content": "An inhibitory effect of chlorpromazine on the enzymatic NADPH-dependent lipid peroxidation in rat liver microsomal fraction was found. This inhibition was caused by the 1) antioxidative effect of hydroxy-derivatives appearing during the oxidative metabolism of chlorpromazine with NADPH-dependent microsomal oxygenases, and by the 2) competition for reduced components of electron-carriers between the NADPH-dependent processes: chlorpromazine metabolism and lipids peroxidation.", "contents": "[Effect of aminazin on the enzymatic oxidation of lipids]. An inhibitory effect of chlorpromazine on the enzymatic NADPH-dependent lipid peroxidation in rat liver microsomal fraction was found. This inhibition was caused by the 1) antioxidative effect of hydroxy-derivatives appearing during the oxidative metabolism of chlorpromazine with NADPH-dependent microsomal oxygenases, and by the 2) competition for reduced components of electron-carriers between the NADPH-dependent processes: chlorpromazine metabolism and lipids peroxidation."}
{"id": "PMID:21013", "title": "The dependence of the lipid bilayer membrane: buffer partition coefficient of pentobarbitone on pH and lipid composition.", "content": "1 The membrane/buffer partition coefficient of [14C]-pentobarbitone has been determined as a function of the lipid composition of bilayer membranes. 2 A new technique based on ultrafiltration gave comparable results to conventional techniques but required less time for equilbration. 3 The membrane/buffer coefficient was independent of pentobarbitone concentration in the range studies. 4 The apparent partition coefficient varied with pH and was a linear function of the degree of dissociation of pentobarbition. 5 Both the charged and uncharged forms of pentobarbitone partitioned into the membrane, the latter to a much greater extent than the former. 6 At low pH the highest partition coefficient observed was in egg phosphatidylcholine bilayer membranes. 7 Incorporation of cholesterol or phosphatidic acid into phosphatidylcholine membranes greatly reduced the partition coefficient. 8 High pressures do not greatly change these partition coefficients.", "contents": "The dependence of the lipid bilayer membrane: buffer partition coefficient of pentobarbitone on pH and lipid composition. 1 The membrane/buffer partition coefficient of [14C]-pentobarbitone has been determined as a function of the lipid composition of bilayer membranes. 2 A new technique based on ultrafiltration gave comparable results to conventional techniques but required less time for equilbration. 3 The membrane/buffer coefficient was independent of pentobarbitone concentration in the range studies. 4 The apparent partition coefficient varied with pH and was a linear function of the degree of dissociation of pentobarbition. 5 Both the charged and uncharged forms of pentobarbitone partitioned into the membrane, the latter to a much greater extent than the former. 6 At low pH the highest partition coefficient observed was in egg phosphatidylcholine bilayer membranes. 7 Incorporation of cholesterol or phosphatidic acid into phosphatidylcholine membranes greatly reduced the partition coefficient. 8 High pressures do not greatly change these partition coefficients."}
{"id": "PMID:21014", "title": "Assessment of the selectivity of OPC-2009, a new beta2-adrenoceptor stimulatn, by the use of the blood-perfused trachea in situ and of the isolated blood-perfused papillary muscle of the dog.", "content": "1 The potency and selectivity of 5-(1-hydroxy-2-isopropylamino)butyl-8-hydroxy carbostyril hydrochloride hemihydrate (OPC-2009), a new beta(2)-adrenoceptor stimulant, was compared with those of isoprenaline, trimetoquinol and salbutamol by the use of blood-perfused tracheal preparations in situ and of blood-perfused papillary muscle preparations of the dog. All drugs were injected intra-arterially.2 All the four drugs decreased tracheal intraluminal pressure (tracheal relaxation) and increased tracheal blood flow in a dose-dependent manner. The four drugs produced a dose-dependent increase in developed tension of papillary muscles. In both preparations the duration of action of isoprenaline and salbutamol was short, whereas that of OPC-2009 and trimetoquinol was long. These effects were antagonized by propranolol.3 Dose-response curves to the four drugs for tracheal relaxation were almost parallel. OPC-2009 was 2.4 times more potent, and trimetoquinol and salbutamol were 2.2 and 6.2 times less potent than isoprenaline in causing tracheal relaxation.4 Dose-response curves to the four drugs for tracheal vasodilatation were also parallel. OPC-2009, trimetoquinol and salbutamol were 3.9, 6.7 and 23 times less potent than isoprenaline.5 Slopes of the dose-response curves to the four drugs for increased developed tension were not parallel; that of OPC-2009 was the least steep, whereas that of isoprenaline was the steepest. Trimetoquinol, salbutamol and OPC-2009 were about 18, 570 and 2400 times less potent than isoprenaline.6 Selectivity calculated from relative potencies indicate that OPC-2009 was about 6000 times, salbutamol about 92 times and trimetoquinol about 8.2 times more selective than isoprenaline for tracheal smooth muscle as compared to ventricular muscle.7 The high potency and selectivity of OPC-2009 for tracheal smooth muscle and its long duration of action suggest its potential usefulness for treatment of bronchial asthma.8 The present results are also compatible with the concept that beta(1)-adrenoceptors in cardiac muscle and beta(2)-adrenoceptors in tracheal and vascular smooth muscle can be distinguished. Furthermore, the results revealed that the beta-adrenoceptors mediating tracheal relaxation and vasodilatation may also be different.", "contents": "Assessment of the selectivity of OPC-2009, a new beta2-adrenoceptor stimulatn, by the use of the blood-perfused trachea in situ and of the isolated blood-perfused papillary muscle of the dog. 1 The potency and selectivity of 5-(1-hydroxy-2-isopropylamino)butyl-8-hydroxy carbostyril hydrochloride hemihydrate (OPC-2009), a new beta(2)-adrenoceptor stimulant, was compared with those of isoprenaline, trimetoquinol and salbutamol by the use of blood-perfused tracheal preparations in situ and of blood-perfused papillary muscle preparations of the dog. All drugs were injected intra-arterially.2 All the four drugs decreased tracheal intraluminal pressure (tracheal relaxation) and increased tracheal blood flow in a dose-dependent manner. The four drugs produced a dose-dependent increase in developed tension of papillary muscles. In both preparations the duration of action of isoprenaline and salbutamol was short, whereas that of OPC-2009 and trimetoquinol was long. These effects were antagonized by propranolol.3 Dose-response curves to the four drugs for tracheal relaxation were almost parallel. OPC-2009 was 2.4 times more potent, and trimetoquinol and salbutamol were 2.2 and 6.2 times less potent than isoprenaline in causing tracheal relaxation.4 Dose-response curves to the four drugs for tracheal vasodilatation were also parallel. OPC-2009, trimetoquinol and salbutamol were 3.9, 6.7 and 23 times less potent than isoprenaline.5 Slopes of the dose-response curves to the four drugs for increased developed tension were not parallel; that of OPC-2009 was the least steep, whereas that of isoprenaline was the steepest. Trimetoquinol, salbutamol and OPC-2009 were about 18, 570 and 2400 times less potent than isoprenaline.6 Selectivity calculated from relative potencies indicate that OPC-2009 was about 6000 times, salbutamol about 92 times and trimetoquinol about 8.2 times more selective than isoprenaline for tracheal smooth muscle as compared to ventricular muscle.7 The high potency and selectivity of OPC-2009 for tracheal smooth muscle and its long duration of action suggest its potential usefulness for treatment of bronchial asthma.8 The present results are also compatible with the concept that beta(1)-adrenoceptors in cardiac muscle and beta(2)-adrenoceptors in tracheal and vascular smooth muscle can be distinguished. Furthermore, the results revealed that the beta-adrenoceptors mediating tracheal relaxation and vasodilatation may also be different."}
{"id": "PMID:21015", "title": "Attitude change during behavioural treatment of sexual inadequacy.", "content": "Attitudes towards 'self' and 'partner' were studied in couples undergoing three different behavioural treatments for sexual inadequacy: systematic desensitization with counselling; guided practice with counselling; and practice with minimal counselling. Factor analysis of semantic differential scales identified five components--general evaluation, anxiety, and three factors relevant to sexual evaluation designated as 'loving', 'sexually attractive' and 'easy to arouse'. Differences in derived factor scores were found which related to sex of rater, identity of complainant, and treatment received; with the treatment combining guided practice with counselling being followed by significantly greater attitude changes.", "contents": "Attitude change during behavioural treatment of sexual inadequacy. Attitudes towards 'self' and 'partner' were studied in couples undergoing three different behavioural treatments for sexual inadequacy: systematic desensitization with counselling; guided practice with counselling; and practice with minimal counselling. Factor analysis of semantic differential scales identified five components--general evaluation, anxiety, and three factors relevant to sexual evaluation designated as 'loving', 'sexually attractive' and 'easy to arouse'. Differences in derived factor scores were found which related to sex of rater, identity of complainant, and treatment received; with the treatment combining guided practice with counselling being followed by significantly greater attitude changes."}
{"id": "PMID:21018", "title": "Histochemical and biochemical characterization of the rat paracervical ganglion.", "content": "The nature and identity of the catecholamines in the paracervical ganglion and superior cervical ganglion small, intensely fluorescent (SIF) cells were investigated using fluorescence histochemical and immunohistochemical techniques. The paracervical ganglion SIF cells were found to contain norepinephrine and the superior cervical ganglion SIF cells, dopamine. The norepinephrine content of the paracervical ganglion SIF cells averaged about 72 ng/ganglion and did not change during the rat estrus cycle. The activity of the enzyme tyrosine hydroxylase in the PCG was very low (about 0.48 nmoles DOPA formed/h/mg protein) and was about 1/50th of the activity of the enzyme in the SCG, where it averaged about 23.90 nmoles DOPA formed/h/mg protein. These experiments suggested that the paracervical ganglion has large numbers of norepinephrine containing SIF cells with a relatively slow turnover of their catecholamine content.", "contents": "Histochemical and biochemical characterization of the rat paracervical ganglion. The nature and identity of the catecholamines in the paracervical ganglion and superior cervical ganglion small, intensely fluorescent (SIF) cells were investigated using fluorescence histochemical and immunohistochemical techniques. The paracervical ganglion SIF cells were found to contain norepinephrine and the superior cervical ganglion SIF cells, dopamine. The norepinephrine content of the paracervical ganglion SIF cells averaged about 72 ng/ganglion and did not change during the rat estrus cycle. The activity of the enzyme tyrosine hydroxylase in the PCG was very low (about 0.48 nmoles DOPA formed/h/mg protein) and was about 1/50th of the activity of the enzyme in the SCG, where it averaged about 23.90 nmoles DOPA formed/h/mg protein. These experiments suggested that the paracervical ganglion has large numbers of norepinephrine containing SIF cells with a relatively slow turnover of their catecholamine content."}
{"id": "PMID:21022", "title": "[Guanyl cyclase activity in the EF-T elongation factor of Escherichia coli].", "content": "Highly purified EF-Ts from E. coli does contain guanylate cyclase activity, which is absent from other purified transfer factors, such as EF-Tu and EF-G. Guanylate cyclase activity has been characterized by its sensitivity to inhibitors and substrate specificity. Although the physicochemical properties of guanylate cyclase are closely related to those of EF-Ts, it does not appear to be a contaminant of this transfer factor, but a specific enzyme. The possible role of guanylate cyclase in protein synthesis is discussed.", "contents": "[Guanyl cyclase activity in the EF-T elongation factor of Escherichia coli]. Highly purified EF-Ts from E. coli does contain guanylate cyclase activity, which is absent from other purified transfer factors, such as EF-Tu and EF-G. Guanylate cyclase activity has been characterized by its sensitivity to inhibitors and substrate specificity. Although the physicochemical properties of guanylate cyclase are closely related to those of EF-Ts, it does not appear to be a contaminant of this transfer factor, but a specific enzyme. The possible role of guanylate cyclase in protein synthesis is discussed."}
{"id": "PMID:21021", "title": "Relationship between urine acidification and intracellular pH in respiratory acidosis.", "content": "The renal net acid excretion (NAE), the blood pH (pHe), the total body intracellular pH (pHi) and the urinary pH (pHu) were calculated in 10 patients with chronic obstructive lung disease and hypercapnia and in 5 normocapnic subjects. The mean value of NAE was significantly higher in hypercapnic subjects than in normocapnic ones. pHe was significantly lower in hypercapnic than in normocapnic subjects. The differences of pHi and pHu between normo and hypercapnic subjects were not significant. NAE is significantly correlated with PaCO2, pHe, pHu and pHi in all the subjects considered together. H+-secretion probably depends on the H+-availability and pHi of tubular cells, but from our results it is not possible to confirm this relationship, because the method used for pHi is fundamentally a measure of muscle-pHi.", "contents": "Relationship between urine acidification and intracellular pH in respiratory acidosis. The renal net acid excretion (NAE), the blood pH (pHe), the total body intracellular pH (pHi) and the urinary pH (pHu) were calculated in 10 patients with chronic obstructive lung disease and hypercapnia and in 5 normocapnic subjects. The mean value of NAE was significantly higher in hypercapnic subjects than in normocapnic ones. pHe was significantly lower in hypercapnic than in normocapnic subjects. The differences of pHi and pHu between normo and hypercapnic subjects were not significant. NAE is significantly correlated with PaCO2, pHe, pHu and pHi in all the subjects considered together. H+-secretion probably depends on the H+-availability and pHi of tubular cells, but from our results it is not possible to confirm this relationship, because the method used for pHi is fundamentally a measure of muscle-pHi."}
{"id": "PMID:21027", "title": "Optimum pH and ionic strength for the assay of cytochrome c oxidase from pea cotyledon mitochondria.", "content": "Cytochrome c oxidase (EC 1.9.3.1) has been solubilized by use of the nonionic detergents were determined for the oxidation of ferrocytochrome c in air. The results indicate that the plant cytochrome c oxidase resembles mammalian preparations in its sensitivity towards ionic strength and pH of the assay buffer.", "contents": "Optimum pH and ionic strength for the assay of cytochrome c oxidase from pea cotyledon mitochondria. Cytochrome c oxidase (EC 1.9.3.1) has been solubilized by use of the nonionic detergents were determined for the oxidation of ferrocytochrome c in air. The results indicate that the plant cytochrome c oxidase resembles mammalian preparations in its sensitivity towards ionic strength and pH of the assay buffer."}
{"id": "PMID:21028", "title": "Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.", "content": "Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis.", "contents": "Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease. Eleven instances of a mixed acid-base disorder consisting of chronic respiratory acidosis and metabolic alkalosis were recognized in eight patients with chronic obstructive lung disease and carbon dioxide retention. Correction of the metabolic alkalosis led to substantial improvement in blood gas values and clinical symptoms. Patients with mixed chronic respiratory acidosis and metabolic alkalosis constitute a common subgroup of patients with chronic obstructive lung disease and carbon dioxide retention; these patients benefit from correction of the metabolic alkalosis."}
{"id": "PMID:21030", "title": "Structural studies on the specific type-14 pneumococcal polysaccharide.", "content": "The structure of the Pneumococcus type-14 capsular polysaccharide has been reinvestigated by using methylation analysis, different specific degradations, and n.m.r. spectroscopy. It is concluded that the polysaccharide is composed of tetrasaccharide repeating-units having the structure: (formula: see text).", "contents": "Structural studies on the specific type-14 pneumococcal polysaccharide. The structure of the Pneumococcus type-14 capsular polysaccharide has been reinvestigated by using methylation analysis, different specific degradations, and n.m.r. spectroscopy. It is concluded that the polysaccharide is composed of tetrasaccharide repeating-units having the structure: (formula: see text)."}
{"id": "PMID:21032", "title": "Left internal mammary--left ventricular fistula after Vineberg operation.", "content": "This communication presents an unusual complication in a patient who underwent the Vineberg procedure with the formation of an internal mammary to left-ventricular fistula, which caused a new apical diastolic murmur. This represents a previously unreported etiology for the appearance of an apical blowing diastolic murmur.", "contents": "Left internal mammary--left ventricular fistula after Vineberg operation. This communication presents an unusual complication in a patient who underwent the Vineberg procedure with the formation of an internal mammary to left-ventricular fistula, which caused a new apical diastolic murmur. This represents a previously unreported etiology for the appearance of an apical blowing diastolic murmur."}
{"id": "PMID:21038", "title": "Clinical usefulness of alkaline phosphatase isoenzyme determinations.", "content": "1. We report on the clinical usefulness of alkaline phosphatase isoenzyme determinations using a combined chemical inhibition method on 731 patient serum specimens exhibiting elevated (greater than 350 U/L) alkaline phosphatase (AP) activity. 2. The relative percentages of the organ-specific alkaline phosphatase activities were computed on the basis of three independent assays: total activity, activity in the presence of 10 mMl-phenylalanine, and activity in the presence of 3.1 M urea. 3. Gamma-glutamyl transferase (GGT) activity assays were also performed on the same specimens. Using an upper reference limit of 30 U/L for GGT and comparing the GGT results with the percent liver AP, we found that the GGT results were 91% sensitive and 60% specific. 4. We conclude that AP isoenzyme determinations are very useful in identifying the organ source(s) responsible for elevated AP values. 5. The reference ranges for several age groups in relation to the adult population and their significance are presented.", "contents": "Clinical usefulness of alkaline phosphatase isoenzyme determinations. 1. We report on the clinical usefulness of alkaline phosphatase isoenzyme determinations using a combined chemical inhibition method on 731 patient serum specimens exhibiting elevated (greater than 350 U/L) alkaline phosphatase (AP) activity. 2. The relative percentages of the organ-specific alkaline phosphatase activities were computed on the basis of three independent assays: total activity, activity in the presence of 10 mMl-phenylalanine, and activity in the presence of 3.1 M urea. 3. Gamma-glutamyl transferase (GGT) activity assays were also performed on the same specimens. Using an upper reference limit of 30 U/L for GGT and comparing the GGT results with the percent liver AP, we found that the GGT results were 91% sensitive and 60% specific. 4. We conclude that AP isoenzyme determinations are very useful in identifying the organ source(s) responsible for elevated AP values. 5. The reference ranges for several age groups in relation to the adult population and their significance are presented."}
{"id": "PMID:21039", "title": "Questionable usefulness of gamma-glutamyl transpeptidase test in legal medicine.", "content": "Because of the high level of GGT activity in semen, the suggestion was made that this enzyme could serve as a test in forensic medical practice; especially in rape cases. Comparisons of GGT and ACP tests revealed, however, that GGT is not sensitive enough and did not show acceptable specificity. One can conclude that GGT cannot be recommended either as a confirmatory test or as a substitute for ACP determinations in rape cases.", "contents": "Questionable usefulness of gamma-glutamyl transpeptidase test in legal medicine. Because of the high level of GGT activity in semen, the suggestion was made that this enzyme could serve as a test in forensic medical practice; especially in rape cases. Comparisons of GGT and ACP tests revealed, however, that GGT is not sensitive enough and did not show acceptable specificity. One can conclude that GGT cannot be recommended either as a confirmatory test or as a substitute for ACP determinations in rape cases."}
{"id": "PMID:21036", "title": "[Enzymatic and serologic study of human trichinosis. Apropos of a recent epidemic in a suburb south of Paris].", "content": "An enzymatic and immunologic study of 18 patients with trichinosis leads to the following conclusions: The stage of muscular invasion in trichinosis is accompanied by a release of cellular enzymes representative of striated muscle fibres in nearly all the cases. This release can be observed by a study of the LDH iso-enzymes at a time when immunological techniques are not always significantly positive. The specific aspect of this phenomenon can be proposed with reservations since there does not exist any interference with other enzymatic systems such as the gamma-GT and furthermore no other evident cause of muscular lysis is present. The existence of a blood hypereosinophilia completes the biological picture. These early modifications of the enzymatic activities are most probably transient.", "contents": "[Enzymatic and serologic study of human trichinosis. Apropos of a recent epidemic in a suburb south of Paris]. An enzymatic and immunologic study of 18 patients with trichinosis leads to the following conclusions: The stage of muscular invasion in trichinosis is accompanied by a release of cellular enzymes representative of striated muscle fibres in nearly all the cases. This release can be observed by a study of the LDH iso-enzymes at a time when immunological techniques are not always significantly positive. The specific aspect of this phenomenon can be proposed with reservations since there does not exist any interference with other enzymatic systems such as the gamma-GT and furthermore no other evident cause of muscular lysis is present. The existence of a blood hypereosinophilia completes the biological picture. These early modifications of the enzymatic activities are most probably transient."}
{"id": "PMID:21040", "title": "Use of different chemical methods for acid phosphatase in cases of rape.", "content": "Generally acid phosphatase (ACP) assay is used for testing cases of alleged rape. Comparison of three different chemical methods for Acid Phosphatase (Andersch's method with p-nitrophenyl-phosphate substrate and tartrate inhibitor (A-Tart), Roy's method with thymolphthalein phosphate substrate (R-TMP), and Babson's method with alphanaphthyl phosphate substrate) indicated that Roy's method (R-TMP) should be the preferred one. This method had both acceptable sensitivity and confirmed specificity. Our data confirmed that the vaginal wash of normal healthy women has a very low level of ACP activity. Because of inconclusive data in the literature regarding this ACP level, a normal and equivocal range of ACP was suggested until more is known about causes and interferences. Possible sources of normal ACP activity in the wash fluids were also indicated.", "contents": "Use of different chemical methods for acid phosphatase in cases of rape. Generally acid phosphatase (ACP) assay is used for testing cases of alleged rape. Comparison of three different chemical methods for Acid Phosphatase (Andersch's method with p-nitrophenyl-phosphate substrate and tartrate inhibitor (A-Tart), Roy's method with thymolphthalein phosphate substrate (R-TMP), and Babson's method with alphanaphthyl phosphate substrate) indicated that Roy's method (R-TMP) should be the preferred one. This method had both acceptable sensitivity and confirmed specificity. Our data confirmed that the vaginal wash of normal healthy women has a very low level of ACP activity. Because of inconclusive data in the literature regarding this ACP level, a normal and equivocal range of ACP was suggested until more is known about causes and interferences. Possible sources of normal ACP activity in the wash fluids were also indicated."}
{"id": "PMID:21041", "title": "Value of alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase, and glutamate dehydrogenase activity measurements (single and combined) in serum in diagnosis of metastasis to the liver.", "content": "We assessed, in 98 patients with cancer, the diagnostic value of measuring serum alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase, and glutamate dehydrogenase activities as an aid to detection of liver metastases. All four enzymes showed diagnostic value, but 5'-nucleotidase appeared to have the greatest. It showed the lowest false-positive results (7.4%) with the highest predictive value of a positive test (85.7%) and agreement (81.3%).. gamma-Glutamyltransferase showed the lowest proportion of false-negative results (2.8%), but was the least specific 35% false-positive results). Analysis of various test combinations showed that the best agreement (77.5%) was obtained when the patients were divided into those who had no or only one abnormal test result, and those who had two or more abnormal test results. However, this was not better than the agreement for 5' nucleotidase alone (81.3%). The agreement of 5'-nucleotidase and gamma-glutamyltransferase (i.e., both tests were positive or negative) was excellent (91.4%), but such agreement included only 67% of the patients with liver metastases.", "contents": "Value of alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase, and glutamate dehydrogenase activity measurements (single and combined) in serum in diagnosis of metastasis to the liver. We assessed, in 98 patients with cancer, the diagnostic value of measuring serum alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase, and glutamate dehydrogenase activities as an aid to detection of liver metastases. All four enzymes showed diagnostic value, but 5'-nucleotidase appeared to have the greatest. It showed the lowest false-positive results (7.4%) with the highest predictive value of a positive test (85.7%) and agreement (81.3%).. gamma-Glutamyltransferase showed the lowest proportion of false-negative results (2.8%), but was the least specific 35% false-positive results). Analysis of various test combinations showed that the best agreement (77.5%) was obtained when the patients were divided into those who had no or only one abnormal test result, and those who had two or more abnormal test results. However, this was not better than the agreement for 5' nucleotidase alone (81.3%). The agreement of 5'-nucleotidase and gamma-glutamyltransferase (i.e., both tests were positive or negative) was excellent (91.4%), but such agreement included only 67% of the patients with liver metastases."}
{"id": "PMID:21042", "title": "Activity and interference effects in measurement of ionized calcium with ion-selective electrodes.", "content": "We assessed the magnitude of the errors in ionized-calcium measurements resulting from changes in electrolyte composition for three different ion-selective electrodes: the Orion Model 93-20, the Radiometer F2112, and the Simon neutral carrier membrane electrode. We attempted to distinguish between errors arising from changes in calcium ion activity and those due to interferences in the electrode response. Variation in sodium ion concentration over the range 100--180 mmol/liter produces changes in apparent ionized-calcium concentration that are largely attributable to activity effects for the Radiometer and Simon electrodes. The Orion electrode is subject to an additional sodium-interference effect. Apparent ionized calcium concentration measurements are independent of pH for the Radiometer electrode but not for the Orion electrode; the Simon electrode exhibits intermediate pH response, which is probably clinically negligible. Magnesium and potassium ions have little effect on ionized calcium concentration measurements, particularly when these ions are incorporated into calibration standards.", "contents": "Activity and interference effects in measurement of ionized calcium with ion-selective electrodes. We assessed the magnitude of the errors in ionized-calcium measurements resulting from changes in electrolyte composition for three different ion-selective electrodes: the Orion Model 93-20, the Radiometer F2112, and the Simon neutral carrier membrane electrode. We attempted to distinguish between errors arising from changes in calcium ion activity and those due to interferences in the electrode response. Variation in sodium ion concentration over the range 100--180 mmol/liter produces changes in apparent ionized-calcium concentration that are largely attributable to activity effects for the Radiometer and Simon electrodes. The Orion electrode is subject to an additional sodium-interference effect. Apparent ionized calcium concentration measurements are independent of pH for the Radiometer electrode but not for the Orion electrode; the Simon electrode exhibits intermediate pH response, which is probably clinically negligible. Magnesium and potassium ions have little effect on ionized calcium concentration measurements, particularly when these ions are incorporated into calibration standards."}
{"id": "PMID:21043", "title": "Effects of ethanol (0.75 g/kg body weight) on the activities of selected enzymes in sera of healthy young adults: 2. Interindividual variations in response of gamma-glutamyltransferase to repeated ethanol challenges.", "content": "We measured individual temporal changes in gamma-glutamyltransferase activity in serum after four consecutive ethanol challenges in each of eight apparently healthy volunteers. Each challenge consisted of ingesting 0.75 g of ethanol per kilogram of body weight on two evenings, followed by five days of abstention during which the activity was assessed at regular intervals. A nine-day abstention period preceded the study, and initial baseline activity was determined. The highest values for the group mean activity were +12%, +11%, +22%, and +18% greater than baseline after the first, second, third, and fourth ethanol challenges, respectively. We noted marked intra-individual and interindividual variation in the enzymic response; peak values ranged from +1% in one subject to +57% in another. The possible causes for these biological variations are discussed.", "contents": "Effects of ethanol (0.75 g/kg body weight) on the activities of selected enzymes in sera of healthy young adults: 2. Interindividual variations in response of gamma-glutamyltransferase to repeated ethanol challenges. We measured individual temporal changes in gamma-glutamyltransferase activity in serum after four consecutive ethanol challenges in each of eight apparently healthy volunteers. Each challenge consisted of ingesting 0.75 g of ethanol per kilogram of body weight on two evenings, followed by five days of abstention during which the activity was assessed at regular intervals. A nine-day abstention period preceded the study, and initial baseline activity was determined. The highest values for the group mean activity were +12%, +11%, +22%, and +18% greater than baseline after the first, second, third, and fourth ethanol challenges, respectively. We noted marked intra-individual and interindividual variation in the enzymic response; peak values ranged from +1% in one subject to +57% in another. The possible causes for these biological variations are discussed."}
{"id": "PMID:21044", "title": "Albumin/calcium association at different pH, as determined by potentiometry.", "content": "Calcium binding by albumin was determined potentiometrically at physiological ionic strength and temperature as a function of pH. The binding data indicate at least 30 different binding sites with different association constants and different H+ interaction. One site appears to be responsible for the major binding at physiological pH and substance concentration of free calcium, together with three other sites that bind with less affinity.", "contents": "Albumin/calcium association at different pH, as determined by potentiometry. Calcium binding by albumin was determined potentiometrically at physiological ionic strength and temperature as a function of pH. The binding data indicate at least 30 different binding sites with different association constants and different H+ interaction. One site appears to be responsible for the major binding at physiological pH and substance concentration of free calcium, together with three other sites that bind with less affinity."}
{"id": "PMID:21045", "title": "The use of tears for diagnosis of GM1 gangliosidosis.", "content": "The properties of beta-galactosidase of tears were investigated and the standard assay system was accomplished. The pH optimum was 4.2. The enzyme had a KM of 8.3 X 10(-4) M. The activity was stimulated by chloride ions and slightly stabilized by bovine serum albumin. The activities of normal individuals were 205 +/- 80 (S.D.) nmol/h/ml. The activity in the tears of the patient with GM1 gangliosidosis decreased to about 20% of normal control and this disease could be diagnosed by the assay of beta-galactosidase in tears.", "contents": "The use of tears for diagnosis of GM1 gangliosidosis. The properties of beta-galactosidase of tears were investigated and the standard assay system was accomplished. The pH optimum was 4.2. The enzyme had a KM of 8.3 X 10(-4) M. The activity was stimulated by chloride ions and slightly stabilized by bovine serum albumin. The activities of normal individuals were 205 +/- 80 (S.D.) nmol/h/ml. The activity in the tears of the patient with GM1 gangliosidosis decreased to about 20% of normal control and this disease could be diagnosed by the assay of beta-galactosidase in tears."}
{"id": "PMID:21046", "title": "Assay of serum free fatty acids by extraction-photometric procedure.", "content": "Reaction conditions for extraction-photometric determination of free fatty acids in serum were studied. The results were found to be influenced by (a) sodium chloride concentration in the copper reagent, (b) the kind of standard solution used, (c) centrifugation of the reaction mixture and (d) serum phospholipids. A micromethod based on the formation of free fatty acids-copper soaps with a stable copper reagent and sensitive indicator for copper, 2-(2-thiazolylazo)-4-methoxyphenol, is described.", "contents": "Assay of serum free fatty acids by extraction-photometric procedure. Reaction conditions for extraction-photometric determination of free fatty acids in serum were studied. The results were found to be influenced by (a) sodium chloride concentration in the copper reagent, (b) the kind of standard solution used, (c) centrifugation of the reaction mixture and (d) serum phospholipids. A micromethod based on the formation of free fatty acids-copper soaps with a stable copper reagent and sensitive indicator for copper, 2-(2-thiazolylazo)-4-methoxyphenol, is described."}
{"id": "PMID:21047", "title": "Sweat testing for cystic fibrosis: errors associated with the in-situ sweat test using chloride ion selective electrodes.", "content": "The in-situ sweat test is prone to errors from various sources. This paper examines errors due to evaporation, absorption of water into the skin, and pressure of the electrode on the skin. Only evaporation caused serious errors. The accuracy and precision when measuring small chloride/sweat samples on the skin are not significantly worse than when measuring bulk solutions.", "contents": "Sweat testing for cystic fibrosis: errors associated with the in-situ sweat test using chloride ion selective electrodes. The in-situ sweat test is prone to errors from various sources. This paper examines errors due to evaporation, absorption of water into the skin, and pressure of the electrode on the skin. Only evaporation caused serious errors. The accuracy and precision when measuring small chloride/sweat samples on the skin are not significantly worse than when measuring bulk solutions."}
{"id": "PMID:21048", "title": "Influence of ions on the antigen-antibody complex formation as measured by radioimmunoassay.", "content": "In this study, using radioimmunoassay techniques, we found that ions at concentrations in the order of 0.1 molar influence the antigen-antibody complex formation. The angiotensin I/anti-angiotensin I reaction was studied in detail. Particularly bivalent cations and anions with a strong chaotropic effect (SCN-, I- and ClO4-) were found to influence strongly the specific immunological reaction. However, NO3- had also a remarkably strong influence. We found that the equilibrium constant, rather than the number of binding sites of the antibody, is influenced by the ions. It should be borne in mind that relatively high concentrations of electrolyte (as compared with the concentrations of antigen and antibody) show this effect. Consequently, this effect is of less practical importance for routine radioimmunoassay than is, for example, the effect of pH. However, this phenomenon shows that the radioimmunoassay technique might be valuable not only for quantization of very low hormone concentrations in biological fluids, but has also important potential applications in physical and protein chemistry. Particularly, the high sensitivity of this technique and the possibility of studying a homogeneous reaction system might give it advantages over other techniques.", "contents": "Influence of ions on the antigen-antibody complex formation as measured by radioimmunoassay. In this study, using radioimmunoassay techniques, we found that ions at concentrations in the order of 0.1 molar influence the antigen-antibody complex formation. The angiotensin I/anti-angiotensin I reaction was studied in detail. Particularly bivalent cations and anions with a strong chaotropic effect (SCN-, I- and ClO4-) were found to influence strongly the specific immunological reaction. However, NO3- had also a remarkably strong influence. We found that the equilibrium constant, rather than the number of binding sites of the antibody, is influenced by the ions. It should be borne in mind that relatively high concentrations of electrolyte (as compared with the concentrations of antigen and antibody) show this effect. Consequently, this effect is of less practical importance for routine radioimmunoassay than is, for example, the effect of pH. However, this phenomenon shows that the radioimmunoassay technique might be valuable not only for quantization of very low hormone concentrations in biological fluids, but has also important potential applications in physical and protein chemistry. Particularly, the high sensitivity of this technique and the possibility of studying a homogeneous reaction system might give it advantages over other techniques."}
{"id": "PMID:21049", "title": "Comparison of soluble and membrane-bound neutral arylamidases from renal cell carcinoma.", "content": "Soluble and membrane-bound neutral arylamidases from renal cell carcinoma were partially purified and their properties were compared. Soluble neutral arylamidase was a heat labile and SH-dependent metalloenzyme. Membrane-bound neutral arylamidase was a rather heat stable metalloenzyme and was activated by Co2+ with changing KM and VMAX. KM values for soluble and membrane-bound neutral arylamidases were different. L-Methionine (5mM) did not affect the enzymic activity of soluble neutral arylamidase, but inhibited 82 percent of the enzymic activity of membrane-bound neutral arylamidase. Molecular weights of soluble and membrane-bound neutral arylamidases by Sephadex G-200 gel filtration were 140000 and 240000, respectively. Soluble and membrane-bound neutral arylamidases from renal cell carcinoma appear to be distinct enzymes.", "contents": "Comparison of soluble and membrane-bound neutral arylamidases from renal cell carcinoma. Soluble and membrane-bound neutral arylamidases from renal cell carcinoma were partially purified and their properties were compared. Soluble neutral arylamidase was a heat labile and SH-dependent metalloenzyme. Membrane-bound neutral arylamidase was a rather heat stable metalloenzyme and was activated by Co2+ with changing KM and VMAX. KM values for soluble and membrane-bound neutral arylamidases were different. L-Methionine (5mM) did not affect the enzymic activity of soluble neutral arylamidase, but inhibited 82 percent of the enzymic activity of membrane-bound neutral arylamidase. Molecular weights of soluble and membrane-bound neutral arylamidases by Sephadex G-200 gel filtration were 140000 and 240000, respectively. Soluble and membrane-bound neutral arylamidases from renal cell carcinoma appear to be distinct enzymes."}
{"id": "PMID:21050", "title": "Comparative activity of sulphatases in human liver on two synthetic substrates.", "content": "Ion-exchange chromatography and gel chromatography manifested the presence of three different forms of sulphatase activity in human liver using 4-methylumbelliferyl sulphate as substrate. Studies with the substrate 4-nitrocatechol sulphate and inhibition experiments with AgNO3 were also performed on these three different forms of sulphatases. This makes it possible to identify the three forms as arylsulphatase A, B, and C. The conclusion is drawn that the 4-methylumbelliferyl sulphate substrate is inadequate to measure the lysosomal arylsulphatases A and B, but it could be used to measure the microsomal arylsulphatase C.", "contents": "Comparative activity of sulphatases in human liver on two synthetic substrates. Ion-exchange chromatography and gel chromatography manifested the presence of three different forms of sulphatase activity in human liver using 4-methylumbelliferyl sulphate as substrate. Studies with the substrate 4-nitrocatechol sulphate and inhibition experiments with AgNO3 were also performed on these three different forms of sulphatases. This makes it possible to identify the three forms as arylsulphatase A, B, and C. The conclusion is drawn that the 4-methylumbelliferyl sulphate substrate is inadequate to measure the lysosomal arylsulphatases A and B, but it could be used to measure the microsomal arylsulphatase C."}
{"id": "PMID:21051", "title": "Some kinetic properites of liver ornithine carbamoyl transferase (OCT) in a patient with OCT deficiency.", "content": "Some kinetic properties of liver OCT from a patient with OCT deficiency were studied. Contrary to controls, in which two pH optima were observed (pH 7.7 and pH 8.5), only the pH optimum of 8.5 could be demonstrated in our patient. From KM studies at pH 7.7 and pH 8.5, the most striking abnormalities in comparison with human controls were (a) a strongly increased KM (ornithine) at pH 7.7, but less pronounced at pH 8.5, (b) a higher VMAX at pH 8.5 compared with the VMAX at pH 7.7 and (c) the absence of substate inhibition at pH 8.5 to ornithine was elevated up to a concentration above approximately 1.5 mM.", "contents": "Some kinetic properites of liver ornithine carbamoyl transferase (OCT) in a patient with OCT deficiency. Some kinetic properties of liver OCT from a patient with OCT deficiency were studied. Contrary to controls, in which two pH optima were observed (pH 7.7 and pH 8.5), only the pH optimum of 8.5 could be demonstrated in our patient. From KM studies at pH 7.7 and pH 8.5, the most striking abnormalities in comparison with human controls were (a) a strongly increased KM (ornithine) at pH 7.7, but less pronounced at pH 8.5, (b) a higher VMAX at pH 8.5 compared with the VMAX at pH 7.7 and (c) the absence of substate inhibition at pH 8.5 to ornithine was elevated up to a concentration above approximately 1.5 mM."}
{"id": "PMID:21056", "title": "The effect of anti-inflammatory and antirheumatic drugs on inflammation in the rat.", "content": "The anti-inflammatory effects of flurbiprofen and a number of other antirheumatic agents were studied in the rat using a model of inflammation, which involved the subcutaneous implantation of polyurethane cubes impregnated with an irritant. Results of acute and chronic studies indicated that flurbiprofen was extremely effective in suppressing both fluid and cellular phases of inflammation and, in this model, was comparable in potency to prednisolone.", "contents": "The effect of anti-inflammatory and antirheumatic drugs on inflammation in the rat. The anti-inflammatory effects of flurbiprofen and a number of other antirheumatic agents were studied in the rat using a model of inflammation, which involved the subcutaneous implantation of polyurethane cubes impregnated with an irritant. Results of acute and chronic studies indicated that flurbiprofen was extremely effective in suppressing both fluid and cellular phases of inflammation and, in this model, was comparable in potency to prednisolone."}
{"id": "PMID:21054", "title": "The effects of urine pH and plasma protein binding on the renal clearance of disopyramide.", "content": "To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2mg/kg) and oral (5 mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4microgram/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding.", "contents": "The effects of urine pH and plasma protein binding on the renal clearance of disopyramide. To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2mg/kg) and oral (5 mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4microgram/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding."}
{"id": "PMID:21059", "title": "Use of EMG biofeedback in behavioral treatment of an obsessive-phobic-depressive syndrome.", "content": "A 25 year old woman who suffered from depression (associated with obsessive, phobic thoughts of animal abuse or neglect) was treated with systematic desensitization in which EMG biofeedback was used to achieve relaxation. EMG responses were also used to aid both the therapist and the patient in the pairing of hierarchical imagery and muscular relaxation during desensitization, EMG responses were particularly useful in detecting rising muscular tension, indicating when visualization of a depression-provoking situation should be terminated. Ratings concerning frequency and intensity of depressive thoughts (made by the patient before and after therapy), as well as 6-month follow-up information, attest to the success of the therapeutic program.", "contents": "Use of EMG biofeedback in behavioral treatment of an obsessive-phobic-depressive syndrome. A 25 year old woman who suffered from depression (associated with obsessive, phobic thoughts of animal abuse or neglect) was treated with systematic desensitization in which EMG biofeedback was used to achieve relaxation. EMG responses were also used to aid both the therapist and the patient in the pairing of hierarchical imagery and muscular relaxation during desensitization, EMG responses were particularly useful in detecting rising muscular tension, indicating when visualization of a depression-provoking situation should be terminated. Ratings concerning frequency and intensity of depressive thoughts (made by the patient before and after therapy), as well as 6-month follow-up information, attest to the success of the therapeutic program."}
{"id": "PMID:21065", "title": "The permissive role of glucocorticoids in the development of ethanol dependence and tolerance.", "content": "In mice chronically treated with ethanol (in a liquid diet containing 6% ethanol ad libitum for 2 weeks), brain tryptophan hydroxylase (TPH) activity was increased (by 30-45% in whole brain), while brain tyrosine hydroxylase activity remained unchanged. Such chronic ethanol treatment also induced susceptibility to audiogenic seizures during withdrawal (60% incidence). When ethanol treatment was given to adrenalectomized (Adx) mice, the increase of brain TPH activity and the development of withdrawal audiogenic seizures were both prevented. In Adx mice receiving daily injections of corticosterone (0.5 mg/mouse), the ethanol-induced increase of brain TPH activity and the occurrence of withdrawal audiogenic seizures were both restored. Similarly, the ethanol-induced increase of liver alcohol dehydrogenase activity (by 60%) was prevented in Adx mice and restored by corticosterone replacement. It was noted that in all three cases replacement with such large doses of the corticoid did not enhance the ethanol effects, but merely restored the effects to the levels observed in intact mice. Apparently, glucocorticoids are required in a permissive role in order for the ethanol effects to occur.", "contents": "The permissive role of glucocorticoids in the development of ethanol dependence and tolerance. In mice chronically treated with ethanol (in a liquid diet containing 6% ethanol ad libitum for 2 weeks), brain tryptophan hydroxylase (TPH) activity was increased (by 30-45% in whole brain), while brain tyrosine hydroxylase activity remained unchanged. Such chronic ethanol treatment also induced susceptibility to audiogenic seizures during withdrawal (60% incidence). When ethanol treatment was given to adrenalectomized (Adx) mice, the increase of brain TPH activity and the development of withdrawal audiogenic seizures were both prevented. In Adx mice receiving daily injections of corticosterone (0.5 mg/mouse), the ethanol-induced increase of brain TPH activity and the occurrence of withdrawal audiogenic seizures were both restored. Similarly, the ethanol-induced increase of liver alcohol dehydrogenase activity (by 60%) was prevented in Adx mice and restored by corticosterone replacement. It was noted that in all three cases replacement with such large doses of the corticoid did not enhance the ethanol effects, but merely restored the effects to the levels observed in intact mice. Apparently, glucocorticoids are required in a permissive role in order for the ethanol effects to occur."}
{"id": "PMID:21068", "title": "Alclofenac: a review of its pharmacological properties and therapeutic efficacy in rheumatoid arthritis and allied rheumatic disorders.", "content": "Alclofenac is a non-steroidal anti-inflammatory agent advocated for use in rheumatoid arthritis, degenerative joint disease and ankylosing spondylitis. Published data to date, suggest that alclofenac 3g daily is comparable in efficacy with aspirin 4.8g daily, phenylbutazone 300 to 600mg daily and indomethacin 150mg daily. In Welsh patients, gastro-intestinal side-effects have generally been less frequent and milder than with the standard comparison drugs, but in other populations differences in the overall incidence of these side-effects have been less marked. Results of a long-term trial, as evidenced by alterations in certain biochemical indications of disease activity, suggest that alclofenac may possibly reduce the severity of the disease itself, but further studies will be needed to confirm this. However, at present alclofenac should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Skin rash is the most frequent side-effect, which in a small proportion of affected patients may be associated with systemic effects. A cutaneous reaction appears to be more likely in patients with a history of previous allergy to penicillin and other drugs.", "contents": "Alclofenac: a review of its pharmacological properties and therapeutic efficacy in rheumatoid arthritis and allied rheumatic disorders. Alclofenac is a non-steroidal anti-inflammatory agent advocated for use in rheumatoid arthritis, degenerative joint disease and ankylosing spondylitis. Published data to date, suggest that alclofenac 3g daily is comparable in efficacy with aspirin 4.8g daily, phenylbutazone 300 to 600mg daily and indomethacin 150mg daily. In Welsh patients, gastro-intestinal side-effects have generally been less frequent and milder than with the standard comparison drugs, but in other populations differences in the overall incidence of these side-effects have been less marked. Results of a long-term trial, as evidenced by alterations in certain biochemical indications of disease activity, suggest that alclofenac may possibly reduce the severity of the disease itself, but further studies will be needed to confirm this. However, at present alclofenac should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Skin rash is the most frequent side-effect, which in a small proportion of affected patients may be associated with systemic effects. A cutaneous reaction appears to be more likely in patients with a history of previous allergy to penicillin and other drugs."}
{"id": "PMID:21070", "title": "Treatment of chronic schizophrenia.", "content": "The comprehensive treatment of schizophrenia requires the full resources of a clinical team that is able to offer treatment for the acute psychotic state in a hospital environment, and appropriate rehabilitation following resolution of the florid symptoms. Following a second or subsequent relapse, maintenance therapy with long-acting injections of depot antipsychotics will be required for an unknown period. Although drugs form an essential part of all treatments, it is essential to examine the environment for precipitating factors and to involve the patient's family in the rehabilitation. Recent studies have reported that some patients still have a relatively poor prognosis; although this proportion may be in the minority, the strain on the whole family of an even moderately handicapped patient can be enormous, and it is important to examine the needs of the whole family in evaluating care within the community. The effect of antipsychotic drugs is much wider that the mere control of acute symptoms and can influence the patterns of social behaviour and rehabilitation, in addition to offering protection against stress. The proper use of depot injections requires that they be kept under constant review. The current widespread practice of prescribing anti-cholinergic drugs on a prophylactic basis, or even as the inital treatment of extrapyramidal side-effects, needs revision.", "contents": "Treatment of chronic schizophrenia. The comprehensive treatment of schizophrenia requires the full resources of a clinical team that is able to offer treatment for the acute psychotic state in a hospital environment, and appropriate rehabilitation following resolution of the florid symptoms. Following a second or subsequent relapse, maintenance therapy with long-acting injections of depot antipsychotics will be required for an unknown period. Although drugs form an essential part of all treatments, it is essential to examine the environment for precipitating factors and to involve the patient's family in the rehabilitation. Recent studies have reported that some patients still have a relatively poor prognosis; although this proportion may be in the minority, the strain on the whole family of an even moderately handicapped patient can be enormous, and it is important to examine the needs of the whole family in evaluating care within the community. The effect of antipsychotic drugs is much wider that the mere control of acute symptoms and can influence the patterns of social behaviour and rehabilitation, in addition to offering protection against stress. The proper use of depot injections requires that they be kept under constant review. The current widespread practice of prescribing anti-cholinergic drugs on a prophylactic basis, or even as the inital treatment of extrapyramidal side-effects, needs revision."}
{"id": "PMID:21073", "title": "Physical studies on the conformation of ribosomal protein S4 from Escherichia coli.", "content": "Proton magnetic resonance, circular dichroism and infrared spectroscopy were used to investigate the secondary and tertiary structure of the 16-S RNA binding protein S4 from Escherichia coli ribosomes. The proton magnetic resonance spectra of protein S4 in ribosomal reconstitution and low-salt buffers were identical and showed little dipolar broadening of the peaks, suggesting that the protein had an open extended structure. A ring-current-shifted apolar methyl resonance in the high-field region of the spectrum, together with a perturbation of the tyrosine ring proton resonance in the low-field region, indicated the existence of a specific tertiary fold in the polypeptide chain. This structure disappeared on lowering the pH below 5 or on heating above 30 degrees C, both processes being reversible. Circular dichroism measurements on protein S4 showed an alpha-helix content of 32% in reconstitution buffer compared with 26% in low-salt buffer. Heating the protein solution in reconstitution buffer above 35 degrees C reversibly disrupted this extra helix. Infrared studies on both solid films and solutions of protein S4 indicated the presence of little or no beta-structure. These results correlate well with the known RNA binding properties of protein S4.", "contents": "Physical studies on the conformation of ribosomal protein S4 from Escherichia coli. Proton magnetic resonance, circular dichroism and infrared spectroscopy were used to investigate the secondary and tertiary structure of the 16-S RNA binding protein S4 from Escherichia coli ribosomes. The proton magnetic resonance spectra of protein S4 in ribosomal reconstitution and low-salt buffers were identical and showed little dipolar broadening of the peaks, suggesting that the protein had an open extended structure. A ring-current-shifted apolar methyl resonance in the high-field region of the spectrum, together with a perturbation of the tyrosine ring proton resonance in the low-field region, indicated the existence of a specific tertiary fold in the polypeptide chain. This structure disappeared on lowering the pH below 5 or on heating above 30 degrees C, both processes being reversible. Circular dichroism measurements on protein S4 showed an alpha-helix content of 32% in reconstitution buffer compared with 26% in low-salt buffer. Heating the protein solution in reconstitution buffer above 35 degrees C reversibly disrupted this extra helix. Infrared studies on both solid films and solutions of protein S4 indicated the presence of little or no beta-structure. These results correlate well with the known RNA binding properties of protein S4."}
{"id": "PMID:21074", "title": "Influence of 1,2,3-benzene-tricarboxylate on pyruvate metabolism in rat-liver mitochondria.", "content": "1,2,3-Benzene-tricarboxylate, a known inhibitor of the mitochondrial tricarboxylate carrier, was found to inhibit pyruvate carboxylation as well as the transport of citrate out of the matrix in rat liver mitochondria incubated with pyruvate. The inhibition of pyruvate carboxylation was observed with both intact mitochondria and with the solubilized pyruvate carboxylase. The inhibition of the pyruvate carboxylase by 1,2,3-benzene-tricarboxylase was not mediated via one of the parameters known to regulate the activity of the enzyme and therefore a direct inhibition of the enzyme by the tricarboxylate was assumed. Since the pyruvate carboxylase is exclusively localized in the mitochondrial matrix space it was concluded that 1,2,3-benzene-tricarboxylate penetrates into this compartment.", "contents": "Influence of 1,2,3-benzene-tricarboxylate on pyruvate metabolism in rat-liver mitochondria. 1,2,3-Benzene-tricarboxylate, a known inhibitor of the mitochondrial tricarboxylate carrier, was found to inhibit pyruvate carboxylation as well as the transport of citrate out of the matrix in rat liver mitochondria incubated with pyruvate. The inhibition of pyruvate carboxylation was observed with both intact mitochondria and with the solubilized pyruvate carboxylase. The inhibition of the pyruvate carboxylase by 1,2,3-benzene-tricarboxylase was not mediated via one of the parameters known to regulate the activity of the enzyme and therefore a direct inhibition of the enzyme by the tricarboxylate was assumed. Since the pyruvate carboxylase is exclusively localized in the mitochondrial matrix space it was concluded that 1,2,3-benzene-tricarboxylate penetrates into this compartment."}
{"id": "PMID:21076", "title": "Prostatic binding protein. A steriod-binding protein secreted by rat prostate.", "content": "Rat prostatic cytosol contains a high concentration of a prostatic binding protein with peculiar steroid-binding properties. Indeed, in spite of a relatively low affinity, charcoal adsorption can be used for its measurement. Furthermore, the binding is not specific for particular steroids and increases very strongly after delipidation. In delipidated cytosol the concentration of the binding site is 3.1 micronmol/g protein and the apparent affinity for pregenolone 1.7 X 10(6) M-1. The high concentration of prostatic binding protein in prostatic fluid shows that this substance is secreted by the prostate. Prostatic binding protein has the following physicochemical characteristics: it is precipitated by ammonium sulfate between 50 and 70% saturation; the elution position from a Sephadex G-100 column corresponds to a molecular weight of 51000; it sediments in sucrose density gradients at 3.7 S and is eluted from DEAE-cellulose columns at about 0.25 M KCl. On polyacrylamide gel electrophoresis the binding activity coincides with the major cytosolic protein band. This band has the same mobility as serum albumin in 7% gels, but a higher mobility in more concentrated gels.", "contents": "Prostatic binding protein. A steriod-binding protein secreted by rat prostate. Rat prostatic cytosol contains a high concentration of a prostatic binding protein with peculiar steroid-binding properties. Indeed, in spite of a relatively low affinity, charcoal adsorption can be used for its measurement. Furthermore, the binding is not specific for particular steroids and increases very strongly after delipidation. In delipidated cytosol the concentration of the binding site is 3.1 micronmol/g protein and the apparent affinity for pregenolone 1.7 X 10(6) M-1. The high concentration of prostatic binding protein in prostatic fluid shows that this substance is secreted by the prostate. Prostatic binding protein has the following physicochemical characteristics: it is precipitated by ammonium sulfate between 50 and 70% saturation; the elution position from a Sephadex G-100 column corresponds to a molecular weight of 51000; it sediments in sucrose density gradients at 3.7 S and is eluted from DEAE-cellulose columns at about 0.25 M KCl. On polyacrylamide gel electrophoresis the binding activity coincides with the major cytosolic protein band. This band has the same mobility as serum albumin in 7% gels, but a higher mobility in more concentrated gels."}
{"id": "PMID:21079", "title": "Yeast pyruvate kinase: a mutant from catalytically insensitive to fructose 1,6-bisphosphate.", "content": "The paper describes some of the characteristic properties of an altered form of pyruvate kinase from a mutant of Saccharomyces cerevisiae. The partially purified enzyme does not require fructose 1,6-bisphosphate for activity but is stabilised in its presence both at low and at high temperatures. The enzyme displays in the absence of fructose 1,6-bisphosphate hyperbolic kinetics with phosphoenolpyruvate (Km, 0.11 mM), ADP (Km, 0.12 mM) and K+ (Km, 11 mM). Sedimentation velocity experiments indicate that the mutated enzyme and the wild type enzyme have S20,w values of 8.9 and 8.6 S respectively. The mutant with the pyruvate insensitive to fructose 1.6-bisphosphate is capable of growing on synthetic media with alcohol or malate as the sole carbon source. The steady-state intracellular levels of phosphoenolpyruvate in the mutant suggest mechanisms that prevent depletion of this metabolite despite an active pyruvate kinase. Spontaneous reversion of this mutant yields clones with normal enzyme activated by fructose 1,6-bisphosphate.", "contents": "Yeast pyruvate kinase: a mutant from catalytically insensitive to fructose 1,6-bisphosphate. The paper describes some of the characteristic properties of an altered form of pyruvate kinase from a mutant of Saccharomyces cerevisiae. The partially purified enzyme does not require fructose 1,6-bisphosphate for activity but is stabilised in its presence both at low and at high temperatures. The enzyme displays in the absence of fructose 1,6-bisphosphate hyperbolic kinetics with phosphoenolpyruvate (Km, 0.11 mM), ADP (Km, 0.12 mM) and K+ (Km, 11 mM). Sedimentation velocity experiments indicate that the mutated enzyme and the wild type enzyme have S20,w values of 8.9 and 8.6 S respectively. The mutant with the pyruvate insensitive to fructose 1.6-bisphosphate is capable of growing on synthetic media with alcohol or malate as the sole carbon source. The steady-state intracellular levels of phosphoenolpyruvate in the mutant suggest mechanisms that prevent depletion of this metabolite despite an active pyruvate kinase. Spontaneous reversion of this mutant yields clones with normal enzyme activated by fructose 1,6-bisphosphate."}
{"id": "PMID:21083", "title": "A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 1. Purification, properties and biological action.", "content": "1. A factor, which amplifies the inductions of several liver enzymes by glucocorticoid, was partially purified from Proteus mirabilis from rat intestine. The factor (amplifier) was completely inactivated by alpha-glucosidase, but not by other glycoside hydrolases, proteases, nucleases or phosphatases tested; it was also hydrolysed by HCl with liberation of reducing sugars. Thus the oligosaccharide in this factor seems to be essential for the amplification. 2. In adrenalectomized rats the amplifier increased the inductions of several liver enzymes, such as tyrosine aminotransferase and leucine aminotransferase, by glucocorticoid. But it did not amplify the induction of tyrosine aminotransferase by glucagon or insulin or the activities of enzymes that are not induced by glucocorticoid. The amplifier by itself did not have any glucocorticoid-like action in adrenalectomized rat. These results show that the amplifier specifically increases the inductions of liver enzymes by glucocorticoid. 3. Since similar amplification was also observed in isolated perfused liver and cultured hepatoma cells in vitro, the amplifier seems to act directly on the target organ or cells.", "contents": "A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 1. Purification, properties and biological action. 1. A factor, which amplifies the inductions of several liver enzymes by glucocorticoid, was partially purified from Proteus mirabilis from rat intestine. The factor (amplifier) was completely inactivated by alpha-glucosidase, but not by other glycoside hydrolases, proteases, nucleases or phosphatases tested; it was also hydrolysed by HCl with liberation of reducing sugars. Thus the oligosaccharide in this factor seems to be essential for the amplification. 2. In adrenalectomized rats the amplifier increased the inductions of several liver enzymes, such as tyrosine aminotransferase and leucine aminotransferase, by glucocorticoid. But it did not amplify the induction of tyrosine aminotransferase by glucagon or insulin or the activities of enzymes that are not induced by glucocorticoid. The amplifier by itself did not have any glucocorticoid-like action in adrenalectomized rat. These results show that the amplifier specifically increases the inductions of liver enzymes by glucocorticoid. 3. Since similar amplification was also observed in isolated perfused liver and cultured hepatoma cells in vitro, the amplifier seems to act directly on the target organ or cells."}
{"id": "PMID:21084", "title": "A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 2. Mechanism of action.", "content": "1. An amplifier of the action of glucocorticoid was purified from Proteus mirabilis as described previously. It was found that it amplified the induction of liver tyrosine aminotransferase by dexamethasone markedly with doses of dexamethasone that caused minimal enzyme induction, but had little effect with doses that caused maximal induction. Thus the amplification may represent a saving of glucocorticoid. The amplification of enzyme activity was brought about by increase in amount of enzyme. 2. The amplification was observed when the amplifier was administered before or with dexamethasone, but not when it was given 2 h after dexamethasone. These results and the finding that actinomycin D inhibited the amplification indicate that the amplifier does not act on the translational level of enzyme induction. 3. It was found that the amplifier increased both incorporation of [3H]dexamethasone into the cytosol and binding of [3H]dexamethasone of cytosol protein and that it decreased decay of the [3H]dexamethasone-protein complex.", "contents": "A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 2. Mechanism of action. 1. An amplifier of the action of glucocorticoid was purified from Proteus mirabilis as described previously. It was found that it amplified the induction of liver tyrosine aminotransferase by dexamethasone markedly with doses of dexamethasone that caused minimal enzyme induction, but had little effect with doses that caused maximal induction. Thus the amplification may represent a saving of glucocorticoid. The amplification of enzyme activity was brought about by increase in amount of enzyme. 2. The amplification was observed when the amplifier was administered before or with dexamethasone, but not when it was given 2 h after dexamethasone. These results and the finding that actinomycin D inhibited the amplification indicate that the amplifier does not act on the translational level of enzyme induction. 3. It was found that the amplifier increased both incorporation of [3H]dexamethasone into the cytosol and binding of [3H]dexamethasone of cytosol protein and that it decreased decay of the [3H]dexamethasone-protein complex."}
{"id": "PMID:21085", "title": "gamma-Glutamyl transpeptidase in rat ascites tumor cell LY-5. Lack of functional correlation of its catalytic activity with the amino acid transport.", "content": "gamma-Glutamyl transpeptidase activity was detected in rat ascites tumor cells (LY-5) suspended in Hanks' balanced saline solution using L-gamma-glutamyl-p-nitroanilide as a substrate. Whole-cell suspension of the tumor cells exhibited full activity of the enzyme without detectable cell disruption under the conditions examined. Various amino acids, transported through specific membrane carriers, did not affect the accessibility of substrate for the enzyme. An inhibitor of sodium-dependent transport systems of amino acids caused no significant change in the rate of enzyme catalysis. Like glutathione or S-methylglutathione, S-acetyldextran (mol. wt 215000) derivative of glutathione, which is believed to be unable to penetrate into intact cells, caused marked inhibition of the rate of p-nitroaniline release from the synthetic substrate by the tumor cells. These data indicated that the active site of the enzyme faced to the outer surface of the cells. gamma-Glutamyl transpeptidase of the tumor cells was successfully affinity-labeled by 6-diazo-5-oxo-L-norleucine, a glutamine analog, without causing detectable change in the viability of the cells under the conditions examined. The rate of transport of alanine, leucine, glycine and glutamine into cells was not affected by the inactivation of this enzyme with the affinity label. Thus, the activity of gamma-glutamyl transpeptidase located on the outer surface of tumor cell membrane does not seem to be requisite for the transport process of amino acids.", "contents": "gamma-Glutamyl transpeptidase in rat ascites tumor cell LY-5. Lack of functional correlation of its catalytic activity with the amino acid transport. gamma-Glutamyl transpeptidase activity was detected in rat ascites tumor cells (LY-5) suspended in Hanks' balanced saline solution using L-gamma-glutamyl-p-nitroanilide as a substrate. Whole-cell suspension of the tumor cells exhibited full activity of the enzyme without detectable cell disruption under the conditions examined. Various amino acids, transported through specific membrane carriers, did not affect the accessibility of substrate for the enzyme. An inhibitor of sodium-dependent transport systems of amino acids caused no significant change in the rate of enzyme catalysis. Like glutathione or S-methylglutathione, S-acetyldextran (mol. wt 215000) derivative of glutathione, which is believed to be unable to penetrate into intact cells, caused marked inhibition of the rate of p-nitroaniline release from the synthetic substrate by the tumor cells. These data indicated that the active site of the enzyme faced to the outer surface of the cells. gamma-Glutamyl transpeptidase of the tumor cells was successfully affinity-labeled by 6-diazo-5-oxo-L-norleucine, a glutamine analog, without causing detectable change in the viability of the cells under the conditions examined. The rate of transport of alanine, leucine, glycine and glutamine into cells was not affected by the inactivation of this enzyme with the affinity label. Thus, the activity of gamma-glutamyl transpeptidase located on the outer surface of tumor cell membrane does not seem to be requisite for the transport process of amino acids."}
{"id": "PMID:21086", "title": "Hydrogen-ion binding by tobacco-mosaic-virus protein polymers.", "content": "Hydrogen ion titration curves of tobacco mosaic virus protein have been measured in various conditions of protein concentration, temperature, ionic strength, and rate of pH change. The polymers present at each stage are deduced from turbidity and sedimentation data, plus published information. A simple semi-quantitative analysis of the curves is given, and the pK values of the two abnormal carboxylates in single helix are estimated as 6.4 and about 7.0. Disks, and some faster-forming unknown polymers in the same size range, have been abnormal carboxylate with pK 6.9. These results are most easily interpreted in terms of electrostatic interactions between carboxylates, probably at the axial ends of the protein subunits.", "contents": "Hydrogen-ion binding by tobacco-mosaic-virus protein polymers. Hydrogen ion titration curves of tobacco mosaic virus protein have been measured in various conditions of protein concentration, temperature, ionic strength, and rate of pH change. The polymers present at each stage are deduced from turbidity and sedimentation data, plus published information. A simple semi-quantitative analysis of the curves is given, and the pK values of the two abnormal carboxylates in single helix are estimated as 6.4 and about 7.0. Disks, and some faster-forming unknown polymers in the same size range, have been abnormal carboxylate with pK 6.9. These results are most easily interpreted in terms of electrostatic interactions between carboxylates, probably at the axial ends of the protein subunits."}
{"id": "PMID:21089", "title": "Ionization behaviour of native apolipoproteins and of their complexes with lecithin. 1. Calorimetric and potentiometric titration of the native apoA-I protein and of the apoA-I protein-dimyristoyl lecithin complex.", "content": "The ionization behaviour of native apoA-I protein is compare to that of its complex with synthetic dimyristoyl lecithin in studies using calorimetric, potentiometric and spectrophotometric titration. In the presence of phospholipids, 10 out of 21 lysines together with 22 acidic residues are masked in the complex. All tyrosines remain accessible to titration below pH 13. The apparent ionization enthalpy of the 11 lysine residues is not affected by the presence of phospholipids. These data are consistent with discrete binding sites located in the apoprotein helical segments as suggested by the model of Segrest et al. [FEBS Lett. 38, 247-253 (1974)]. A tentative localisation of lysine, arginine, aspartic acid and glutamic acid residues directly involved in phospholipid binding is suggested, assuming that such helical regions are involved in apoprotein-phospholipid association.", "contents": "Ionization behaviour of native apolipoproteins and of their complexes with lecithin. 1. Calorimetric and potentiometric titration of the native apoA-I protein and of the apoA-I protein-dimyristoyl lecithin complex. The ionization behaviour of native apoA-I protein is compare to that of its complex with synthetic dimyristoyl lecithin in studies using calorimetric, potentiometric and spectrophotometric titration. In the presence of phospholipids, 10 out of 21 lysines together with 22 acidic residues are masked in the complex. All tyrosines remain accessible to titration below pH 13. The apparent ionization enthalpy of the 11 lysine residues is not affected by the presence of phospholipids. These data are consistent with discrete binding sites located in the apoprotein helical segments as suggested by the model of Segrest et al. [FEBS Lett. 38, 247-253 (1974)]. A tentative localisation of lysine, arginine, aspartic acid and glutamic acid residues directly involved in phospholipid binding is suggested, assuming that such helical regions are involved in apoprotein-phospholipid association."}
{"id": "PMID:21090", "title": "Ionization behaviour of native apolipoproteins and of their complexes with lecithin. 2. Potentiometric titration of the native apo-A-II, apoC-I, apoC-III proteins and of their complexes with dimyristoyl lecithin.", "content": "A comparison of the ionization behaviour of the human apoA-II, apoC-I, apoC-III proteins and of their complexes with dimyristoyl lecithin is based on potentiometric titration of the basic and acidic residues and spectrophotometric titration of the phenolic groups. Experimental data suggest that a number of lysine, arginine, aspartic acid and glutamic acid residues are masked in the complexes. For each of these amino acids and in all three proteins the number of masked residues is consistent with the content of those regions predicted to be involved in lipid binding by the model of Segrest et al. [FEBS Lett. 38, 247-253 (1974)]. These data taken together with the results of calorimetric and titration experiments with the apoA-I protein reported in the accompanying article [Rosseneu et al. (1977) Eur. J. Biochem. 79, 251-257] strongly support the general nature of the proposed model and further suggest that ionic interactions have some role in the formation of the dimyristoyl lecithin/apolipoprotein complexes.", "contents": "Ionization behaviour of native apolipoproteins and of their complexes with lecithin. 2. Potentiometric titration of the native apo-A-II, apoC-I, apoC-III proteins and of their complexes with dimyristoyl lecithin. A comparison of the ionization behaviour of the human apoA-II, apoC-I, apoC-III proteins and of their complexes with dimyristoyl lecithin is based on potentiometric titration of the basic and acidic residues and spectrophotometric titration of the phenolic groups. Experimental data suggest that a number of lysine, arginine, aspartic acid and glutamic acid residues are masked in the complexes. For each of these amino acids and in all three proteins the number of masked residues is consistent with the content of those regions predicted to be involved in lipid binding by the model of Segrest et al. [FEBS Lett. 38, 247-253 (1974)]. These data taken together with the results of calorimetric and titration experiments with the apoA-I protein reported in the accompanying article [Rosseneu et al. (1977) Eur. J. Biochem. 79, 251-257] strongly support the general nature of the proposed model and further suggest that ionic interactions have some role in the formation of the dimyristoyl lecithin/apolipoprotein complexes."}
{"id": "PMID:21092", "title": "Substrate specificity via ternary complex formation with glutamate dehydrogenase.", "content": "Very littly discrimination is observed in the binary binding of dicarboxylic acid substrate analogues to glutamate dehydrogenase as monitored by proton nuclear magnetic resonance. Variation in length, charge, bulkiness and conformational rigidity resulted in only a factor of five variation in KD and apparent relaxation time, T2. Upon titration of the binary enzyme-ligand complex with coenzyme to form the ternary enzyme-ligand-coenzyme complex strong discrimination is observed. Coenzyme binds tightly only when the correct substrate is present, otherwise it binds 10 to 150 times more weakly.", "contents": "Substrate specificity via ternary complex formation with glutamate dehydrogenase. Very littly discrimination is observed in the binary binding of dicarboxylic acid substrate analogues to glutamate dehydrogenase as monitored by proton nuclear magnetic resonance. Variation in length, charge, bulkiness and conformational rigidity resulted in only a factor of five variation in KD and apparent relaxation time, T2. Upon titration of the binary enzyme-ligand complex with coenzyme to form the ternary enzyme-ligand-coenzyme complex strong discrimination is observed. Coenzyme binds tightly only when the correct substrate is present, otherwise it binds 10 to 150 times more weakly."}
{"id": "PMID:21093", "title": "Reversible graft versus host reaction as cause of erythrophagic splenomegaly in a child?", "content": "The case history of a 9 months old infant with hepatosplenomegaly, pancytopnaenia and disturbances of clotting and cellular immune reactivity is reported. The spleen was removed and showed striking erythrophagocytosis by proliferating histiocytes, typical of \"familial erythrophagocytic reticulosis\" (Farquhar). A graft-versus-host reaction is discussed as a possible underlying cause. The favourable clinical course and full recovery point to an interrelation with primary hypersplenism.", "contents": "Reversible graft versus host reaction as cause of erythrophagic splenomegaly in a child? The case history of a 9 months old infant with hepatosplenomegaly, pancytopnaenia and disturbances of clotting and cellular immune reactivity is reported. The spleen was removed and showed striking erythrophagocytosis by proliferating histiocytes, typical of \"familial erythrophagocytic reticulosis\" (Farquhar). A graft-versus-host reaction is discussed as a possible underlying cause. The favourable clinical course and full recovery point to an interrelation with primary hypersplenism."}
{"id": "PMID:21094", "title": "Interstitial cystitis. Observations on diagnosis and on treatment with anti-inflammatory drugs, particularly benzydamine.", "content": "Interstitial cystitis is often missed on \"routine\" cystoscopy. If the disease is suspected, the bladder must be observed twice during complete filling. An anti-inflammatory drug, Benzydamine, has given mixed results but in view of its low toxicity it is worth trying in any patient with severe symptoms.", "contents": "Interstitial cystitis. Observations on diagnosis and on treatment with anti-inflammatory drugs, particularly benzydamine. Interstitial cystitis is often missed on \"routine\" cystoscopy. If the disease is suspected, the bladder must be observed twice during complete filling. An anti-inflammatory drug, Benzydamine, has given mixed results but in view of its low toxicity it is worth trying in any patient with severe symptoms."}
{"id": "PMID:21095", "title": "Prune belly syndrome: treatment of terminal renal failure by hemodialysis and renal transplantation.", "content": "The second case of successful renal transplantation in a patient with \"prune belly\" syndrome is reported. In spite of early aggressive surgical approach in the management of this disease terminal renal failure frequently ensues. Hemodialysis and renal transplantation have offered new possibilities of prolonging life in these patients. The success of renal transplantation depends on the anatomic and functional state of the lower urinary tract. Pretransplant urologic examination is extremely important for the evaluation of urinary tract abnormalities.", "contents": "Prune belly syndrome: treatment of terminal renal failure by hemodialysis and renal transplantation. The second case of successful renal transplantation in a patient with \"prune belly\" syndrome is reported. In spite of early aggressive surgical approach in the management of this disease terminal renal failure frequently ensues. Hemodialysis and renal transplantation have offered new possibilities of prolonging life in these patients. The success of renal transplantation depends on the anatomic and functional state of the lower urinary tract. Pretransplant urologic examination is extremely important for the evaluation of urinary tract abnormalities."}
{"id": "PMID:21097", "title": "Acid mucopolysaccharides in fibroblast cultures. 4. 35S-sulfate incorporation in dependence on pH-value cell density and lactate.", "content": "Cultures of embryonic rat fibroblasts were incubated with 35S-sulfate at pH 6.6 and 7.4 (Eagle medium, Hepes buffer) for 48 hours. The MPS were isolated and fractionated. Determination of hexuronic acid was done according to BITTER and MUIR, measuring of sulfate incorporation by liquid scintillation counting. 1. HS, Ch-6-S and DS showed different synthesis rates. They rised at increasing cell density and were lower at pH 6.6 than at 7.4. 2. At pH 6.6 the sulfate incorporation rates (de novo-synthesis) of HS, Ch-6-S and DS are lowered. The percent increase of the MPS fractions at pH 6.6 and their specific activities are explained by individual differences in the unlabelled MPS pools as well as by differences in the rates of synthesis and catabolism. The cell density also has an influence on that. Increase of the MPS at pH 6.6 is by mainly due to an inhibition of catabolism. 3. Contrary to CH-6-S and DS heparan sulfate is catabolized more slowly at high cell densities. 4. The volume of the unlabelled MPS pool is modified by lactate at pH 6.6, e.g. it effectuates enhancement of the DS pool at low cell densities. De novo-synthesis and specific activity are scarcely influenced. CH-6-S and DS catabolism are considerably inhibited, their total amount is increased. The relative synthesis rate of DS is enhanced by lactate. 5. The possible importance of the results for inflammatory processes and wound healing is mentioned.", "contents": "Acid mucopolysaccharides in fibroblast cultures. 4. 35S-sulfate incorporation in dependence on pH-value cell density and lactate. Cultures of embryonic rat fibroblasts were incubated with 35S-sulfate at pH 6.6 and 7.4 (Eagle medium, Hepes buffer) for 48 hours. The MPS were isolated and fractionated. Determination of hexuronic acid was done according to BITTER and MUIR, measuring of sulfate incorporation by liquid scintillation counting. 1. HS, Ch-6-S and DS showed different synthesis rates. They rised at increasing cell density and were lower at pH 6.6 than at 7.4. 2. At pH 6.6 the sulfate incorporation rates (de novo-synthesis) of HS, Ch-6-S and DS are lowered. The percent increase of the MPS fractions at pH 6.6 and their specific activities are explained by individual differences in the unlabelled MPS pools as well as by differences in the rates of synthesis and catabolism. The cell density also has an influence on that. Increase of the MPS at pH 6.6 is by mainly due to an inhibition of catabolism. 3. Contrary to CH-6-S and DS heparan sulfate is catabolized more slowly at high cell densities. 4. The volume of the unlabelled MPS pool is modified by lactate at pH 6.6, e.g. it effectuates enhancement of the DS pool at low cell densities. De novo-synthesis and specific activity are scarcely influenced. CH-6-S and DS catabolism are considerably inhibited, their total amount is increased. The relative synthesis rate of DS is enhanced by lactate. 5. The possible importance of the results for inflammatory processes and wound healing is mentioned."}
{"id": "PMID:21106", "title": "[Analysis of the effect of bicarbonate on taste receptor sensitivity to organic acids].", "content": "Addition of NaHCO3 or NaOH to the solutions of lactic or pyruvic acids decreased threshold concentrations of H+ ions and increased intensity of afferent impulsation in the cat chroda tympani nerve. In spite of the fact that the concentrations of both lactate and pyruvate anions with the presence of NaOH and NaHCO3 are the same at equal pH values the observed changes of the receptors responses were more intensive if NaHCO3 had been added. Therefore the influence of NaHCO3 on the perception of organic acids depends not only on its buffer properties but, probably, on direct action of CO2 appearing as the result of interaction of NaHCO3 and acids, as well. This assumption was confirmed by the data on high sensitivity of the cat tongue receptors for the carbon dioxide.", "contents": "[Analysis of the effect of bicarbonate on taste receptor sensitivity to organic acids]. Addition of NaHCO3 or NaOH to the solutions of lactic or pyruvic acids decreased threshold concentrations of H+ ions and increased intensity of afferent impulsation in the cat chroda tympani nerve. In spite of the fact that the concentrations of both lactate and pyruvate anions with the presence of NaOH and NaHCO3 are the same at equal pH values the observed changes of the receptors responses were more intensive if NaHCO3 had been added. Therefore the influence of NaHCO3 on the perception of organic acids depends not only on its buffer properties but, probably, on direct action of CO2 appearing as the result of interaction of NaHCO3 and acids, as well. This assumption was confirmed by the data on high sensitivity of the cat tongue receptors for the carbon dioxide."}
{"id": "PMID:21115", "title": "Degradation and liquefaction effect of streptokinase-Streptodornase and stabilized trypsin on necroses, crusts of fibrinoid, purulent exudate and clotted blood from leg ulcers.", "content": "Necrotic materials most frequently found in leg ulcers, including crusts with fibrinogen, pus and blood clots, were exposed to solutions of streptokinase-streptodornase and stabilized crystalline trypsin respectively. The investigations were performed at the temperatures of 26 degrees and 33 degrees C, representing the extreme values of the temperature range found in leg ulcers (arteriosclerotic ulcers, stasis ulcers) and at the pH corresponding to that of the enzyme preparations in wet dressings. Streptokinase-streptodornase demonstrated in vitro a more potent proteolytic activity than crystalline trypsin on necroses, crusts of fibrinoid and purulent exudate, which were more rapidly and thoroughly broken up. Both enzyme preparations were, however, equally effective on three-day-old blood clots.", "contents": "Degradation and liquefaction effect of streptokinase-Streptodornase and stabilized trypsin on necroses, crusts of fibrinoid, purulent exudate and clotted blood from leg ulcers. Necrotic materials most frequently found in leg ulcers, including crusts with fibrinogen, pus and blood clots, were exposed to solutions of streptokinase-streptodornase and stabilized crystalline trypsin respectively. The investigations were performed at the temperatures of 26 degrees and 33 degrees C, representing the extreme values of the temperature range found in leg ulcers (arteriosclerotic ulcers, stasis ulcers) and at the pH corresponding to that of the enzyme preparations in wet dressings. Streptokinase-streptodornase demonstrated in vitro a more potent proteolytic activity than crystalline trypsin on necroses, crusts of fibrinoid and purulent exudate, which were more rapidly and thoroughly broken up. Both enzyme preparations were, however, equally effective on three-day-old blood clots."}
{"id": "PMID:21116", "title": "Anxiety states in family practice: an evaluation of the need for antidepressant as well as anxiolytic therapy.", "content": "Patients attending their family practitioner with emotional disturbance manifesting predominantly as anxiety were treated once daily for 4 weeks with either a pure anxiolytic, potassium clorazepate, or a formulation of a specific antidepressant together with an anxiolytic, fluphenazine/nortriptyline, in accordance with a double-blind, completely randomized design. After the first week the patients receiving fluphenazine/nortriptyline were showing a better response in terms of total symptomatology as well as anxiety, tension and depression taken separately, and after 4 weeks treatment this trend reached statistically significant levels on both the physicans' ratings and the patients' self-ratings for overall symptomatology (p less than 0-05) as well as anxiety and tension on the physicians' scale (p less than 0-01). Side-effects were infrequent, with the exception of drowsiness which was complained of by 42% of the patients receiving clorazepate. Although simple and convenient to take, a once daily benzodiazepine formulation of fixed dose is likely to be too inflexible to achieve optimal therapeutic effect in many patients. These results are in accord with accumulating evidence for the importance of a depressive aetiology underlying the majority of so-called anxiety states in family practice. Anxiolytic, in the absence of specific antidepressant, therapy is unlikely to be adequate for these patients, and may lead to long-term palliative use of benzodiazepines incurring a risk of dependence.", "contents": "Anxiety states in family practice: an evaluation of the need for antidepressant as well as anxiolytic therapy. Patients attending their family practitioner with emotional disturbance manifesting predominantly as anxiety were treated once daily for 4 weeks with either a pure anxiolytic, potassium clorazepate, or a formulation of a specific antidepressant together with an anxiolytic, fluphenazine/nortriptyline, in accordance with a double-blind, completely randomized design. After the first week the patients receiving fluphenazine/nortriptyline were showing a better response in terms of total symptomatology as well as anxiety, tension and depression taken separately, and after 4 weeks treatment this trend reached statistically significant levels on both the physicans' ratings and the patients' self-ratings for overall symptomatology (p less than 0-05) as well as anxiety and tension on the physicians' scale (p less than 0-01). Side-effects were infrequent, with the exception of drowsiness which was complained of by 42% of the patients receiving clorazepate. Although simple and convenient to take, a once daily benzodiazepine formulation of fixed dose is likely to be too inflexible to achieve optimal therapeutic effect in many patients. These results are in accord with accumulating evidence for the importance of a depressive aetiology underlying the majority of so-called anxiety states in family practice. Anxiolytic, in the absence of specific antidepressant, therapy is unlikely to be adequate for these patients, and may lead to long-term palliative use of benzodiazepines incurring a risk of dependence."}
{"id": "PMID:21117", "title": "Therapy of alveococcosis in man.", "content": "Diagnostic, therapeutic and prognostic aspects are interpreted on the basis of two cases of Echinococcus alveolaris. Both patients had undergone partial hepatectomy and were subsequently treated chemotherapeutically. In one case dehydroemetine and mebendazole (Vermox, Janssen), and in the other case metrifonate (Bilarcil, Bayer A.G.) were used. The diagnosis of alveococcosis of the liver was demonstrated in one case histologically on the occasion of appendectomy, and in the other case by the indirect immunofluorescence test and passive haemagglutination. In case of suspected alveococcosis these serological are imperative, as they are the most reliable methods of demonstrating this disease. The latest trend in theraphy aims at a combination of surgery and chemotherapy. Mebendazole seems to be promising as an anthelmintic agent for the treatment of alveococcosis. Remission of the disease was obtained in either case.", "contents": "Therapy of alveococcosis in man. Diagnostic, therapeutic and prognostic aspects are interpreted on the basis of two cases of Echinococcus alveolaris. Both patients had undergone partial hepatectomy and were subsequently treated chemotherapeutically. In one case dehydroemetine and mebendazole (Vermox, Janssen), and in the other case metrifonate (Bilarcil, Bayer A.G.) were used. The diagnosis of alveococcosis of the liver was demonstrated in one case histologically on the occasion of appendectomy, and in the other case by the indirect immunofluorescence test and passive haemagglutination. In case of suspected alveococcosis these serological are imperative, as they are the most reliable methods of demonstrating this disease. The latest trend in theraphy aims at a combination of surgery and chemotherapy. Mebendazole seems to be promising as an anthelmintic agent for the treatment of alveococcosis. Remission of the disease was obtained in either case."}
{"id": "PMID:21120", "title": "[The orthostatic hypotension in patients treated with antihypertensive drugs (author's transl)].", "content": "Occasional or recurrent episodes of orthostatic hypotension were observed in 58 out of 584 hypertensive patients treated with alpha-methyldopa, beta-blockers and clonidine alone or associated with diuretics and/or hydralazine and/or reserpine. They occurred more frequently in the elderly. In none dicardial ischaemia. In only 3 cases it caused drowsiness and in 2 transient T wave inversion. These results suggest that postural hypotension does not contraindicate the continuation of antihypertensive treatment.", "contents": "[The orthostatic hypotension in patients treated with antihypertensive drugs (author's transl)]. Occasional or recurrent episodes of orthostatic hypotension were observed in 58 out of 584 hypertensive patients treated with alpha-methyldopa, beta-blockers and clonidine alone or associated with diuretics and/or hydralazine and/or reserpine. They occurred more frequently in the elderly. In none dicardial ischaemia. In only 3 cases it caused drowsiness and in 2 transient T wave inversion. These results suggest that postural hypotension does not contraindicate the continuation of antihypertensive treatment."}
{"id": "PMID:21122", "title": "[Management and monitoring of multiple pregnancies (author's transl)].", "content": "The fetal prognosis in multiple pregnancies can be improved by a multifaceted antenatal program which includes early diagnosis prior to 28 weeks gestation, follow-up of multiple pregnancies in the high risk antenatal clinic, early discontinuation of work, treatment of pre-eclampsia, bed rest in hospital between 28 and 33 weeks and sometimes cerclage, prophylactic and therapeutic administration of labour inhibiting drugs, speedy delivery of the second twin and immediate pediatric care. Bed rest and administration of labour inhibiting drugs are the most important points of this program. With this combination, the utero-placental perfusion can be improved. The gestation can be prolonged and the incidence of small weight neonates and the incidence of the perinatal mortality can be reduced. Since even a large antenatal clinic only cares for a small number of multiple pregnancies, a multicentre study to determine the optimal management of multiple pregnancies is urgently required. Multiple pregnancies had too little attention in modern perinatal medicine and deserve all our attention for an improvement of their outcome.", "contents": "[Management and monitoring of multiple pregnancies (author's transl)]. The fetal prognosis in multiple pregnancies can be improved by a multifaceted antenatal program which includes early diagnosis prior to 28 weeks gestation, follow-up of multiple pregnancies in the high risk antenatal clinic, early discontinuation of work, treatment of pre-eclampsia, bed rest in hospital between 28 and 33 weeks and sometimes cerclage, prophylactic and therapeutic administration of labour inhibiting drugs, speedy delivery of the second twin and immediate pediatric care. Bed rest and administration of labour inhibiting drugs are the most important points of this program. With this combination, the utero-placental perfusion can be improved. The gestation can be prolonged and the incidence of small weight neonates and the incidence of the perinatal mortality can be reduced. Since even a large antenatal clinic only cares for a small number of multiple pregnancies, a multicentre study to determine the optimal management of multiple pregnancies is urgently required. Multiple pregnancies had too little attention in modern perinatal medicine and deserve all our attention for an improvement of their outcome."}
{"id": "PMID:21123", "title": "[Clinical polymorphism and ceruloplasmin variants in hepatolenticular degeneration].", "content": "The relationship between differences in the clinical polymorphism of hepatolenticular degeneration (Wilson's disease) and characteristics of CP (ceruloplasmin) structural changes were investigated. The comparative study of Wilson's disease patients revealed two forms of clinical development of this disease which differ from each other by the expression of the visceral symptoms preceding the establishment of the typical neurological picture. The peptide map analysis of tryptic hydrolysates of the CP from individual patients has demonstrated the altered peptide patterns in five cases. Clinical and genetic heterogeneity of Wilson's disease is discussed.", "contents": "[Clinical polymorphism and ceruloplasmin variants in hepatolenticular degeneration]. The relationship between differences in the clinical polymorphism of hepatolenticular degeneration (Wilson's disease) and characteristics of CP (ceruloplasmin) structural changes were investigated. The comparative study of Wilson's disease patients revealed two forms of clinical development of this disease which differ from each other by the expression of the visceral symptoms preceding the establishment of the typical neurological picture. The peptide map analysis of tryptic hydrolysates of the CP from individual patients has demonstrated the altered peptide patterns in five cases. Clinical and genetic heterogeneity of Wilson's disease is discussed."}
{"id": "PMID:21124", "title": "Ditazole and platelets III. Effect of ditazole on tumor-cell induced thrombocytopenia and on bleeding time in mice.", "content": "Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) inhibits in vivo platelet aggregation induced in mice by intravenous injection of cells derived from an experimental tumor, the Lewis lung carcinoma. Such a protective effect of ditazole could not be observed when the number of circulating platelets dropped slowly following intramuscular implantation and spontaneous dissemination of the same cancer cells. These results support previous observations suggesting a different mechanism for the thrombocytopenia observed after intravenous and intramuscular injection of cancer cells. Tail transection bleeding time of normal mice is significantly prolonged by ditazole, a finding at variance with that reported in rats.", "contents": "Ditazole and platelets III. Effect of ditazole on tumor-cell induced thrombocytopenia and on bleeding time in mice. Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) inhibits in vivo platelet aggregation induced in mice by intravenous injection of cells derived from an experimental tumor, the Lewis lung carcinoma. Such a protective effect of ditazole could not be observed when the number of circulating platelets dropped slowly following intramuscular implantation and spontaneous dissemination of the same cancer cells. These results support previous observations suggesting a different mechanism for the thrombocytopenia observed after intravenous and intramuscular injection of cancer cells. Tail transection bleeding time of normal mice is significantly prolonged by ditazole, a finding at variance with that reported in rats."}
{"id": "PMID:21125", "title": "[Effects of a new minor tranquilizer, 10-chloro-3-methyl-1 1b-(2-chlorophenyl)-2,3,5,6,7,11b-hexahydrobenzo [6,7]-1,4-diazepino [5,4-b]-oxazol-6-one (CS-386), on the after-discharge and behavior induced by electrical stimulation of the amygdala in freely-moving cats (author's transl)].", "content": "Effects of a new minor tranquilizer, CS-386, on the after-discharge(AD) and behavior induced by amygdaloid electrical stimulation in freely-moving cats were compared with those of cloxazolam, oxazolam, diazepam, chlordiazepoxide, phenobarbital and chlorphromazine. Effects on change of the AD threshold and duration and on facial twitching, salivation and tonic-clonic convulsion were investigated. CS-386, cloxazolam and oxazolam inhibited amygdaloid AD. CS-386 had the most potent inhibitory effect. These drugs depressed all behavior described above. Diazepam had no effects on the AD threshold, but decreased the AD duration and inhibited the behavior. Chlordiazepoxide had no apparent effects on amygdaloid AD and on facial twitching. Salivation was inhibited with high doses of administration. Phenobarbital shortened the AD duration and at a high dose elevated the AD threshold. This drug also inhibited salivation, but inhibitory effects on other behavior required doses as high as 90 mg/kg. These results suggest that CS-386, cloxazolam and oxazolam are compounds belonging to a classification different from that of chlorpromazine. CS-386 in particular, is a more potent drug chlordiazepoxide, diazepam and phenobarbital and acts on the amygdala itself.", "contents": "[Effects of a new minor tranquilizer, 10-chloro-3-methyl-1 1b-(2-chlorophenyl)-2,3,5,6,7,11b-hexahydrobenzo [6,7]-1,4-diazepino [5,4-b]-oxazol-6-one (CS-386), on the after-discharge and behavior induced by electrical stimulation of the amygdala in freely-moving cats (author's transl)]. Effects of a new minor tranquilizer, CS-386, on the after-discharge(AD) and behavior induced by amygdaloid electrical stimulation in freely-moving cats were compared with those of cloxazolam, oxazolam, diazepam, chlordiazepoxide, phenobarbital and chlorphromazine. Effects on change of the AD threshold and duration and on facial twitching, salivation and tonic-clonic convulsion were investigated. CS-386, cloxazolam and oxazolam inhibited amygdaloid AD. CS-386 had the most potent inhibitory effect. These drugs depressed all behavior described above. Diazepam had no effects on the AD threshold, but decreased the AD duration and inhibited the behavior. Chlordiazepoxide had no apparent effects on amygdaloid AD and on facial twitching. Salivation was inhibited with high doses of administration. Phenobarbital shortened the AD duration and at a high dose elevated the AD threshold. This drug also inhibited salivation, but inhibitory effects on other behavior required doses as high as 90 mg/kg. These results suggest that CS-386, cloxazolam and oxazolam are compounds belonging to a classification different from that of chlorpromazine. CS-386 in particular, is a more potent drug chlordiazepoxide, diazepam and phenobarbital and acts on the amygdala itself."}
{"id": "PMID:21126", "title": "[Studies on monoamine oxidase. (Report 37) Effects of oxygen concentration on rat liver and brain monoamine oxidase (author's transl)].", "content": "MAO activity in rat brain mitochondria with tyramine as substrate at 100% oxygen concentration was three times as much as that at 20%. When serotonin served as substrate, difference in activities between the two oxygen concentrations was not significant. Similar results were obtained when rat liver MAO was used as the enzyme source. At 100% oxygen concentration, pargyline showed the most potent inhibition of MAO activity in liver mitochondria with tyramine as substrate, but inhibitions caused by pheniprazine and harmaline were not remarkable. At 100% oxygen concentration, harmaline showed the most potent inhibition of MAO activity in the liver when serotonin served as substrate, while inhibitions of the MAO activity by pargyline and pheniprazine were weak. At 20% oxygen concentration, harmaline showed the most potent inhibition of MAO activity in the brain when serotonin was used as substrate. These inhibitions were studied using Lineweaver-Burk plots. Pargyline revealed a noncompetitive inhibition to MAO activity in liver and brain with tyramine and serotonin as substrate, harmaline a competitive inhibition to MAO activity in liver and brain with tyramine as substrate, while noncompetitive inhibition to MAO activity in liver and brain was evident when serotonin was used as the substrate.", "contents": "[Studies on monoamine oxidase. (Report 37) Effects of oxygen concentration on rat liver and brain monoamine oxidase (author's transl)]. MAO activity in rat brain mitochondria with tyramine as substrate at 100% oxygen concentration was three times as much as that at 20%. When serotonin served as substrate, difference in activities between the two oxygen concentrations was not significant. Similar results were obtained when rat liver MAO was used as the enzyme source. At 100% oxygen concentration, pargyline showed the most potent inhibition of MAO activity in liver mitochondria with tyramine as substrate, but inhibitions caused by pheniprazine and harmaline were not remarkable. At 100% oxygen concentration, harmaline showed the most potent inhibition of MAO activity in the liver when serotonin served as substrate, while inhibitions of the MAO activity by pargyline and pheniprazine were weak. At 20% oxygen concentration, harmaline showed the most potent inhibition of MAO activity in the brain when serotonin was used as substrate. These inhibitions were studied using Lineweaver-Burk plots. Pargyline revealed a noncompetitive inhibition to MAO activity in liver and brain with tyramine and serotonin as substrate, harmaline a competitive inhibition to MAO activity in liver and brain with tyramine as substrate, while noncompetitive inhibition to MAO activity in liver and brain was evident when serotonin was used as the substrate."}
{"id": "PMID:21127", "title": "[Effects of minor tranquilizers and neuroleptics on open-field behavior in rats (author's transl)].", "content": "Minor tranquilizers (diazepam, nitrazepam, oxazepam, bromazepam, medazepam, fludiazepam, meprobamate) at low doses increased ambulation score to 145 approximately 288% of control rats. Nitrazepam, diazepam and bromazepam which are potent, clinically prescribed minor tranquilizers increased the ambulation at lower doses than was seen with the other drugs. Fludiazepam and nitrazepam showed a maximum increase in ambulation at the same dose. Fludiazepam, nitrazepam and diazepam proved to have potent inhibitory effects on defecation. Trifluperidol, haloperidol and ID-4708 (a new butyrophenone derivative) and chlorpromazine when given at low doses reduced ambulation, while at higher doses defecation was inhibited. These four drugs reduced ambulation and elicited a recover in rates of defecation in methamphetamine treated rats. Clozapine, thioridazine and floropipamide inhibited defecation at nearly the same doses which reduced ambulation in rats not given the methamphetamine tratment. These three durugs reduced ambulation, but did not produce a recovery in the defecation rates in methamphetamine-treated rats. These results indicate that neuroleptics such as clozapine which rarely induce extrapyramidal side-effects when clinically prescribed, inhibit defecation at nearly the same doses which reduce ambulation. In methamphetamine-treated rats, haloperidol was 31 times more potent than chlorpromazine in inhibiting activity noted with ambulation. This ratio in open-field test was close to the ratio of potency of these drugs as antipsychotic clinically prescribed agents.", "contents": "[Effects of minor tranquilizers and neuroleptics on open-field behavior in rats (author's transl)]. Minor tranquilizers (diazepam, nitrazepam, oxazepam, bromazepam, medazepam, fludiazepam, meprobamate) at low doses increased ambulation score to 145 approximately 288% of control rats. Nitrazepam, diazepam and bromazepam which are potent, clinically prescribed minor tranquilizers increased the ambulation at lower doses than was seen with the other drugs. Fludiazepam and nitrazepam showed a maximum increase in ambulation at the same dose. Fludiazepam, nitrazepam and diazepam proved to have potent inhibitory effects on defecation. Trifluperidol, haloperidol and ID-4708 (a new butyrophenone derivative) and chlorpromazine when given at low doses reduced ambulation, while at higher doses defecation was inhibited. These four drugs reduced ambulation and elicited a recover in rates of defecation in methamphetamine treated rats. Clozapine, thioridazine and floropipamide inhibited defecation at nearly the same doses which reduced ambulation in rats not given the methamphetamine tratment. These three durugs reduced ambulation, but did not produce a recovery in the defecation rates in methamphetamine-treated rats. These results indicate that neuroleptics such as clozapine which rarely induce extrapyramidal side-effects when clinically prescribed, inhibit defecation at nearly the same doses which reduce ambulation. In methamphetamine-treated rats, haloperidol was 31 times more potent than chlorpromazine in inhibiting activity noted with ambulation. This ratio in open-field test was close to the ratio of potency of these drugs as antipsychotic clinically prescribed agents."}
{"id": "PMID:21129", "title": "[Calcium containing antacids and acid rebound. Testing with intragastric titration and extragastric measurement of pH].", "content": "Intragastric titration with the pH being measured extragastrically is a method both precise and highly qualified for clinical trials of antacids and quantitative analysis of gastric secretion. In 12 patients with duodenal ulcer, acid secretion was measured by intragastric titration both before and after adminstration of a Ca-Mg-containing antacid. Acid secretion was found to be significantly lower after administration of the Ca-Mg-containing antacid, a so-called acid rebound could not be demonstrated.", "contents": "[Calcium containing antacids and acid rebound. Testing with intragastric titration and extragastric measurement of pH]. Intragastric titration with the pH being measured extragastrically is a method both precise and highly qualified for clinical trials of antacids and quantitative analysis of gastric secretion. In 12 patients with duodenal ulcer, acid secretion was measured by intragastric titration both before and after adminstration of a Ca-Mg-containing antacid. Acid secretion was found to be significantly lower after administration of the Ca-Mg-containing antacid, a so-called acid rebound could not be demonstrated."}
{"id": "PMID:21130", "title": "[The clinical picture of lactate acidosis. 5. Lactatemia without acidosis. Conclusions].", "content": "Several inherited metabolic diseases are accompanied by a greater or lesser increase in blood lactate concentration under certain metabolic conditions. These diseases are glycogenosis type I (glocuse-6-phosphate deficiency), fructose-1,6-diphosphatase deficiency, glucose-induced hyperlactate emia, idiopathic lactate acidosis. The conditions are discussed when hyperlactate emia develops. Very large increases in blood lactate concentration are found during muscular activity, lactate concentrations can be as much as 20 mmol/l under these conditions. Regarding these values, the increase in blood lactate concentration during intravenous carbohydrate infusion is minimum, even in the case of fructose infusions (1-4 mmol/l). Therapeutical measures for treatment of increased lactate concentration are discussed. A causal therapy is optimum; however, the precondition is a definite diagnosis. Besides bicarbonate infusions (or infusions of other alkalizing substances) dialysis seems to be a favourable therapy in certain cases. In future, prognosis of lactate emia should be better if the diagnostic measures and differential diagnosis are improved.", "contents": "[The clinical picture of lactate acidosis. 5. Lactatemia without acidosis. Conclusions]. Several inherited metabolic diseases are accompanied by a greater or lesser increase in blood lactate concentration under certain metabolic conditions. These diseases are glycogenosis type I (glocuse-6-phosphate deficiency), fructose-1,6-diphosphatase deficiency, glucose-induced hyperlactate emia, idiopathic lactate acidosis. The conditions are discussed when hyperlactate emia develops. Very large increases in blood lactate concentration are found during muscular activity, lactate concentrations can be as much as 20 mmol/l under these conditions. Regarding these values, the increase in blood lactate concentration during intravenous carbohydrate infusion is minimum, even in the case of fructose infusions (1-4 mmol/l). Therapeutical measures for treatment of increased lactate concentration are discussed. A causal therapy is optimum; however, the precondition is a definite diagnosis. Besides bicarbonate infusions (or infusions of other alkalizing substances) dialysis seems to be a favourable therapy in certain cases. In future, prognosis of lactate emia should be better if the diagnostic measures and differential diagnosis are improved."}
{"id": "PMID:21131", "title": "[Neurological-psychiatrical and muscular manifestations of vasculitis nodosa (author's transl)].", "content": "A general review on vasculitis nodosa of report in literature since the work of Strammler 1958 is given. The neurological and psychiatric manifestations of the disease are completely dealt with, whereas dermatological, ophthalmological and otological aspects are brieftly mentioned. Varieties of diffuse and localized cerebral, as well as peripheral syndromes are described. The neuropathological findings are also discussed extensively.", "contents": "[Neurological-psychiatrical and muscular manifestations of vasculitis nodosa (author's transl)]. A general review on vasculitis nodosa of report in literature since the work of Strammler 1958 is given. The neurological and psychiatric manifestations of the disease are completely dealt with, whereas dermatological, ophthalmological and otological aspects are brieftly mentioned. Varieties of diffuse and localized cerebral, as well as peripheral syndromes are described. The neuropathological findings are also discussed extensively."}
{"id": "PMID:21140", "title": "Primary care and physician extenders in affluent countries.", "content": "The worldwide growth of specialization in medicine has led to a perceived shortage of primary care. A major response in the United States has been the training of physician extenders (both physician assistants and nurse practitioners). Other industrialized countries have rejected this approach, in favor of strengthening general medical practice through continuing education, provision of ancillary personnel, use of health centers, and by other methods. Developing countries use doctor-substitutes as a reasonable adjustment to their lack of economic resources. All countries use ancillary personnel for selected procedures, such as midwifery, which involve only limited judgment and decision making. The American strategy on use of doctor-substitutes for primary care, however, follows from unwillingness to train greater numbers of primary care physicians and to require them to serve in places of need. This results in an inequitable concentration of doctor-substitutes on service to the poor in both urban and rural areas.", "contents": "Primary care and physician extenders in affluent countries. The worldwide growth of specialization in medicine has led to a perceived shortage of primary care. A major response in the United States has been the training of physician extenders (both physician assistants and nurse practitioners). Other industrialized countries have rejected this approach, in favor of strengthening general medical practice through continuing education, provision of ancillary personnel, use of health centers, and by other methods. Developing countries use doctor-substitutes as a reasonable adjustment to their lack of economic resources. All countries use ancillary personnel for selected procedures, such as midwifery, which involve only limited judgment and decision making. The American strategy on use of doctor-substitutes for primary care, however, follows from unwillingness to train greater numbers of primary care physicians and to require them to serve in places of need. This results in an inequitable concentration of doctor-substitutes on service to the poor in both urban and rural areas."}
{"id": "PMID:21142", "title": "Is the alkaline cleavage of disulfide bonds in peptides an alpha-beta elimination reaction or a hydrolysis?", "content": "The cleavage of oxidized glutathione by alkali has been studied as representative of the cleavage of protein disulfides. This process is quite different when studied in 10-4N or 2-10-1N NaOH. At low alkali concentration no spectral changes are noted; at higher hydroxyl concentration the appearance of persulfide groups (followed at 335 nm), the formation of thiocyanate (arising from cold cyanolysis of persulfide groups) and the absorbance at 240 nm follow the same kinetics. The amount of half-cystine, recovered as cysteic acid after a 3-h reaction, is significantly lower than calculated. These results confirm that oxidized glutathione undergoes beta-elimination at high pH values, and that persulfide groups absorb not only at 335 nm (as already known) but also at 240 nm where, under our conditions, the contribution of other absorbing species is not very high.", "contents": "Is the alkaline cleavage of disulfide bonds in peptides an alpha-beta elimination reaction or a hydrolysis? The cleavage of oxidized glutathione by alkali has been studied as representative of the cleavage of protein disulfides. This process is quite different when studied in 10-4N or 2-10-1N NaOH. At low alkali concentration no spectral changes are noted; at higher hydroxyl concentration the appearance of persulfide groups (followed at 335 nm), the formation of thiocyanate (arising from cold cyanolysis of persulfide groups) and the absorbance at 240 nm follow the same kinetics. The amount of half-cystine, recovered as cysteic acid after a 3-h reaction, is significantly lower than calculated. These results confirm that oxidized glutathione undergoes beta-elimination at high pH values, and that persulfide groups absorb not only at 335 nm (as already known) but also at 240 nm where, under our conditions, the contribution of other absorbing species is not very high."}
{"id": "PMID:21143", "title": "Modification of lipoxygenase by hydrogen peroxide and photooxidation.", "content": "The kinetic study of fluorescence stopped-flow method suggested that the interaction between lipoxygenase and H2O2 is consistent with a simple irreversible one-step mechanism. The activation energy of the reaction was 7.2 kcal/mol. Participation of an ionizable group with pK about 8.8, possibly a histidine residue, was suggested from the pH-dependence of the rate constant. No further fluorescence quenching of lipoxygenase was observed when the product was added to the lipoxygenase solution before mixing the lipoxygenase and H2O2 solutions. The fluorescence quenching of lipoxygenase by H2O2 was in parallel with the inactivation of the enzyme. Hydroperoxylinoleic acid strongly protects the inactivation of lipoxygenase caused by H2O2. These results are consistent with an interpretation that OH- and/or O- - are produced when the iron of the enzyme is oxidized by H2O2, which in turn will attack some amino acid essential for the enzyme activity. The pH-dependence of the inactivation rate constant of photooxidation of lipoxygenase sensitized by methylene blue indicated that an ionizable group with pK about 8.8 is concerned with the enzymatic activity. In contrast to the inactivation of lipoxygenase by H2O2, the product protected the inactivation of the enzyme by photooxidation only at high concentration.", "contents": "Modification of lipoxygenase by hydrogen peroxide and photooxidation. The kinetic study of fluorescence stopped-flow method suggested that the interaction between lipoxygenase and H2O2 is consistent with a simple irreversible one-step mechanism. The activation energy of the reaction was 7.2 kcal/mol. Participation of an ionizable group with pK about 8.8, possibly a histidine residue, was suggested from the pH-dependence of the rate constant. No further fluorescence quenching of lipoxygenase was observed when the product was added to the lipoxygenase solution before mixing the lipoxygenase and H2O2 solutions. The fluorescence quenching of lipoxygenase by H2O2 was in parallel with the inactivation of the enzyme. Hydroperoxylinoleic acid strongly protects the inactivation of lipoxygenase caused by H2O2. These results are consistent with an interpretation that OH- and/or O- - are produced when the iron of the enzyme is oxidized by H2O2, which in turn will attack some amino acid essential for the enzyme activity. The pH-dependence of the inactivation rate constant of photooxidation of lipoxygenase sensitized by methylene blue indicated that an ionizable group with pK about 8.8 is concerned with the enzymatic activity. In contrast to the inactivation of lipoxygenase by H2O2, the product protected the inactivation of the enzyme by photooxidation only at high concentration."}
{"id": "PMID:21144", "title": "The effect of additives on the free radical formation in aqueous solutions of ascorbic acid.", "content": "The relative rate constants for the decay of ascorbate free radical in aqueous solutions in the presence of heavy metal ions, hydrogen peroxide and sulphite were measured the ESR-spectroscopy. The oxidation of ascorbic acid showed a strong pH dependence, reaching a maximum rate at pH 9.6. It was shown that the ascorbic acid radical decay generally follows overall second order kinetics, being however first order in the presence of hydrogen peroxide. The protective effect of sulphur dioxide is proposed to have nutritional implications.", "contents": "The effect of additives on the free radical formation in aqueous solutions of ascorbic acid. The relative rate constants for the decay of ascorbate free radical in aqueous solutions in the presence of heavy metal ions, hydrogen peroxide and sulphite were measured the ESR-spectroscopy. The oxidation of ascorbic acid showed a strong pH dependence, reaching a maximum rate at pH 9.6. It was shown that the ascorbic acid radical decay generally follows overall second order kinetics, being however first order in the presence of hydrogen peroxide. The protective effect of sulphur dioxide is proposed to have nutritional implications."}
{"id": "PMID:21145", "title": "Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit.", "content": "The effect of timolol, propranolol, epinephrine, and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All four agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the two beta-adrenergic blocking agents. In alpha-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol, and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (three/day) over an 8-day period. The concentration of timolol in the acqueous humor after topical application of effective hypotensive doses was relatively high as compared to that found in plasma. In addition, topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of beta-adrenergic blocking agents in glaucoma are discussed.", "contents": "Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit. The effect of timolol, propranolol, epinephrine, and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All four agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the two beta-adrenergic blocking agents. In alpha-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol, and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (three/day) over an 8-day period. The concentration of timolol in the acqueous humor after topical application of effective hypotensive doses was relatively high as compared to that found in plasma. In addition, topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of beta-adrenergic blocking agents in glaucoma are discussed."}
{"id": "PMID:21150", "title": "Studies on avian erythrocyte metabolism. VII. Effect of inositol pentaphosphate and other organic phosphates on oxygen affinity of the embryonic and adult-type hemoglobins of the turkey embryo.", "content": "The effects of 2, 3-diphosphoglyceric acid (2, 3-DPG), adenosine triphosphate (ATP), inositol tetraphosphate (ITP), inositol pentaphosphate (IPP), and inositol hexaphosphate (IHP) on oxygen affinity of whole stripped hemoglobin (WSH), hemoglobin H (Hb-H; hatching hemoglobin), hemoglobin A (Hb-A), and hemoglobin D (Hb-D) isolated from erythrocytes (RBC) of the 25-day turkey embryo have been studied. The order of the decrease in oxygen affinity induced by these organic phosphates, at molar ratios of phosphate compound to hemoglobin (tetramer) between 2 and 4, is 2, 3-DPG less than ATP less than ITP less than IPP less than IHP. 2, 3-DPG shows a slightly greater effect on reducing oxygen affinity of Hb-H than on either adult-type hemoglobin. The effect of IPP upon lowering the oxygen affinity of either WSH, Hb-H, Hb-A, or Hb-D is approximately 20 percent less than IHP. The effects of the various organic phosphates upon the Hill constant, n, of these purified hemoglobins is variable but appears to reach a maximum when the molar ratio of organic phosphate to hemoglobin (tetramer) is 2 or greater. None of the physiologically occurring organic phosphates has a significant preferential interaction with any specific hemoglobin. These experiments strengthen and support our earlier conclusion, that the changes in whole blood oxygen affinity which occur during avian development result from the changes in composition of the intraerythrocytic organic phosphates.", "contents": "Studies on avian erythrocyte metabolism. VII. Effect of inositol pentaphosphate and other organic phosphates on oxygen affinity of the embryonic and adult-type hemoglobins of the turkey embryo. The effects of 2, 3-diphosphoglyceric acid (2, 3-DPG), adenosine triphosphate (ATP), inositol tetraphosphate (ITP), inositol pentaphosphate (IPP), and inositol hexaphosphate (IHP) on oxygen affinity of whole stripped hemoglobin (WSH), hemoglobin H (Hb-H; hatching hemoglobin), hemoglobin A (Hb-A), and hemoglobin D (Hb-D) isolated from erythrocytes (RBC) of the 25-day turkey embryo have been studied. The order of the decrease in oxygen affinity induced by these organic phosphates, at molar ratios of phosphate compound to hemoglobin (tetramer) between 2 and 4, is 2, 3-DPG less than ATP less than ITP less than IPP less than IHP. 2, 3-DPG shows a slightly greater effect on reducing oxygen affinity of Hb-H than on either adult-type hemoglobin. The effect of IPP upon lowering the oxygen affinity of either WSH, Hb-H, Hb-A, or Hb-D is approximately 20 percent less than IHP. The effects of the various organic phosphates upon the Hill constant, n, of these purified hemoglobins is variable but appears to reach a maximum when the molar ratio of organic phosphate to hemoglobin (tetramer) is 2 or greater. None of the physiologically occurring organic phosphates has a significant preferential interaction with any specific hemoglobin. These experiments strengthen and support our earlier conclusion, that the changes in whole blood oxygen affinity which occur during avian development result from the changes in composition of the intraerythrocytic organic phosphates."}
{"id": "PMID:21147", "title": "Studies on the physico-chemical properties of alhagain.", "content": "The protease isolated jawasee shrub was found to hydrolyze egg albumin, casein, haemoglobin and gelatin optimally near neutral pH. Fibrin, bovin serum albumin, skin albumin and skin mucoids were hydrolyzed at slightly alkaline pH, while skin globulins were hydrolyzed at slightly acidic pH. The enzyme had no effect of fibrous collagen. The optimum conditions for the hydrolysis of 50 mg of egg albumin were found to be 50 mg of alhagain at pH 6.0 and 45 degrees C for 30 minutes. A Km value of 4.4 X 10(-3) M was obtained from the Lineweaver-Burk plot for the hydrolysis of egg albumin. The enzyme was found to be comparatively thermostable and was most stable at pH 4.7. Ultraviolet irradiation exhibited no appreciable effect on the enzyme activity. The ultraviolet absorption spectrum of alhagain in bi-distilled water resembles those of bromelain and trypsin. The sugar-containing enzyme was found to have a molecular weight of 20,650. The enzymeconsists of 189 amino acid residues per molecule, neutral and acidic amino acids being present in high concentrations. The partial specific volume of alhagain was calculated to be 0.743 ml/g from its amino acid composition. Phenylalnine and arginine formed the amino terminal amino acids of alhagain, while aspartic acid and serine were identified as its carboxy terminal amino acids. Results are discussed with relation to other plant proteases.", "contents": "Studies on the physico-chemical properties of alhagain. The protease isolated jawasee shrub was found to hydrolyze egg albumin, casein, haemoglobin and gelatin optimally near neutral pH. Fibrin, bovin serum albumin, skin albumin and skin mucoids were hydrolyzed at slightly alkaline pH, while skin globulins were hydrolyzed at slightly acidic pH. The enzyme had no effect of fibrous collagen. The optimum conditions for the hydrolysis of 50 mg of egg albumin were found to be 50 mg of alhagain at pH 6.0 and 45 degrees C for 30 minutes. A Km value of 4.4 X 10(-3) M was obtained from the Lineweaver-Burk plot for the hydrolysis of egg albumin. The enzyme was found to be comparatively thermostable and was most stable at pH 4.7. Ultraviolet irradiation exhibited no appreciable effect on the enzyme activity. The ultraviolet absorption spectrum of alhagain in bi-distilled water resembles those of bromelain and trypsin. The sugar-containing enzyme was found to have a molecular weight of 20,650. The enzymeconsists of 189 amino acid residues per molecule, neutral and acidic amino acids being present in high concentrations. The partial specific volume of alhagain was calculated to be 0.743 ml/g from its amino acid composition. Phenylalnine and arginine formed the amino terminal amino acids of alhagain, while aspartic acid and serine were identified as its carboxy terminal amino acids. Results are discussed with relation to other plant proteases."}
{"id": "PMID:21148", "title": "Stearoyl-CoA desaturase in mitochondrial membrane fractions.", "content": "Several arguments suggested the possibility that the stearoyl-CoA desaturase might be located in the outer mitochondrial membrane in addition to its well presence in the microsomes. In the present investigation, preparations of rat liver microsomes and submitochondrial fractions (outer and inner membranes) were comparatively studied with respect to their stearoyl-CoA desaturase activities. Each fraction has been characterized by determinations of enzymic and chemical markers. This study revealed that while the activity of the stearoyl-CoA desaturase in microsomes was comparable to that found in other laboratories, a very low level of activity was detected in the mitochondrial outer membrane. The possible implications of the lack of stearoyl-CoA desaturase in mitochondria are discussed with respect to the lipid metabolism of these organelles.", "contents": "Stearoyl-CoA desaturase in mitochondrial membrane fractions. Several arguments suggested the possibility that the stearoyl-CoA desaturase might be located in the outer mitochondrial membrane in addition to its well presence in the microsomes. In the present investigation, preparations of rat liver microsomes and submitochondrial fractions (outer and inner membranes) were comparatively studied with respect to their stearoyl-CoA desaturase activities. Each fraction has been characterized by determinations of enzymic and chemical markers. This study revealed that while the activity of the stearoyl-CoA desaturase in microsomes was comparable to that found in other laboratories, a very low level of activity was detected in the mitochondrial outer membrane. The possible implications of the lack of stearoyl-CoA desaturase in mitochondria are discussed with respect to the lipid metabolism of these organelles."}
{"id": "PMID:21152", "title": "Comparison of the activities of some dehydrogenases in the juxtaglomerular complex of kidneys of Wistar rats and desert rats (Meriones unguiculati).", "content": "The authors compared the enzyme histochemical activities of some dehydrogenases in the macula densa, the Goormaghtigh cells and the epithelioid (or juxtaglomerular cells in the kidneys of desert rodents (Mongolian Gerbils) with those of the Wistar rats. The macula cells (Table 1), which in the Wistar rats are clearly distinct from the non specific epithelial cells of the distal convolution, show, in the desert rats, noticeable fluctuations. Their enzyme histochemical reactions are often weaker than those of the distal convolution cells, with the exception of the NAD-tetrazolium-reductase activity. The Goormaghtigh cells (Table 2) in the kidneys of the Meriones have a much larger enzymatic spectrum than in the Wistar rats. Here also, we find functional variations in the examined desert species. In the epithelioid cells (Table 3) we observed a somewhat weaker enzymatic activity in the Meriones. These cells contain no secretion granules, this making their diagnosis difficult.", "contents": "Comparison of the activities of some dehydrogenases in the juxtaglomerular complex of kidneys of Wistar rats and desert rats (Meriones unguiculati). The authors compared the enzyme histochemical activities of some dehydrogenases in the macula densa, the Goormaghtigh cells and the epithelioid (or juxtaglomerular cells in the kidneys of desert rodents (Mongolian Gerbils) with those of the Wistar rats. The macula cells (Table 1), which in the Wistar rats are clearly distinct from the non specific epithelial cells of the distal convolution, show, in the desert rats, noticeable fluctuations. Their enzyme histochemical reactions are often weaker than those of the distal convolution cells, with the exception of the NAD-tetrazolium-reductase activity. The Goormaghtigh cells (Table 2) in the kidneys of the Meriones have a much larger enzymatic spectrum than in the Wistar rats. Here also, we find functional variations in the examined desert species. In the epithelioid cells (Table 3) we observed a somewhat weaker enzymatic activity in the Meriones. These cells contain no secretion granules, this making their diagnosis difficult."}
{"id": "PMID:21154", "title": "Influence of temperature on hemoglobin-ligand interaction in whole blood.", "content": "Temperature-dependent change in hemoglobin-oxygen affinity was measured as a function of hemoglobin-oxygen saturation. In addition, the CO2 Bohr factor and fixed acid Bohr factor were measured as a function of saturation of temperatures of 23, 30, 37, and 44 degrees C. Measurements were made on normal blood and blood with reduced 2,3-diphosphoglycerate (DPG). The influence of temperature is greatest at low saturation and is enhanced slightly by DPG depletion. The CO2 Bohr factor is increased at high temperatures; this is primarily due to increased carbamino formation with rising temperature, especially at lower oxygen saturation. The effect of DPG on oxygen affinity is reduced at a high temperature and elevated at low temperature. These diverse effects of temperature on hemoglobin-ligand interaction require consideration in assessing oxygen delivery when temperature is increased or decreased.", "contents": "Influence of temperature on hemoglobin-ligand interaction in whole blood. Temperature-dependent change in hemoglobin-oxygen affinity was measured as a function of hemoglobin-oxygen saturation. In addition, the CO2 Bohr factor and fixed acid Bohr factor were measured as a function of saturation of temperatures of 23, 30, 37, and 44 degrees C. Measurements were made on normal blood and blood with reduced 2,3-diphosphoglycerate (DPG). The influence of temperature is greatest at low saturation and is enhanced slightly by DPG depletion. The CO2 Bohr factor is increased at high temperatures; this is primarily due to increased carbamino formation with rising temperature, especially at lower oxygen saturation. The effect of DPG on oxygen affinity is reduced at a high temperature and elevated at low temperature. These diverse effects of temperature on hemoglobin-ligand interaction require consideration in assessing oxygen delivery when temperature is increased or decreased."}
{"id": "PMID:21157", "title": "Regulatory mutations in the Klebsiella aerogenes structural gene for glutamine synthetase.", "content": "Glutamine synthetase could be repressed several hundredfold rather than 6- to 10-fold as previously reported. Ammonia was not the primary repression signal for glutamine synthetase. Repression appeared to be mediated by a high level of glutamine and probably by a high ratio of glutamine to alpha-ketoglutarate. Mutations in glnA (the structural gene for glutamine synthetase) were seen to fall into three phenotypic groups: glutamine auxotrophs that produced no detectable glnA product; glutamine auxotrophs that produced a glnA product lacking enzymatic activity (and hence repressibility by ammonia) but were repressible under appropriate conditions; and glutamine synthetase regulatory mutants, whose glnA product was enzymatically active and not repressible under any conditions.", "contents": "Regulatory mutations in the Klebsiella aerogenes structural gene for glutamine synthetase. Glutamine synthetase could be repressed several hundredfold rather than 6- to 10-fold as previously reported. Ammonia was not the primary repression signal for glutamine synthetase. Repression appeared to be mediated by a high level of glutamine and probably by a high ratio of glutamine to alpha-ketoglutarate. Mutations in glnA (the structural gene for glutamine synthetase) were seen to fall into three phenotypic groups: glutamine auxotrophs that produced no detectable glnA product; glutamine auxotrophs that produced a glnA product lacking enzymatic activity (and hence repressibility by ammonia) but were repressible under appropriate conditions; and glutamine synthetase regulatory mutants, whose glnA product was enzymatically active and not repressible under any conditions."}
{"id": "PMID:21158", "title": "Autogenous regulation of the synthesis of glutamine synthetase in Klebsiella aerogenes.", "content": "We isolated an F' episome of Escherichia coli carrying the glnA+ gene from K. aerogenes and an F' episome of E. coli carrying the glnA4 allele from K. aerogenes responsible for the constitutive synthesis of glutamine synthetase. Complementation tests with these episomes showed that the glnA4 mutation (leading to the constitutive synthesis of active glutamine synthetase) was in the gene identified by mutations glnA20, glnA51, and glnA5 as the structural gene for glutamine synthetase. By using these merodiploid strains we were able to show that the glnA51 mutation lead to the synthesis of a glutamine synthetase that lacked enzymatic activity but fully retained its regulatory properties. Finally, we discuss a model that explains the several phenotypes associated with mutations such as glnA4 located within the structural gene for glutamine synthetase leading to constitutive synthesis of active glutamine synthetase.", "contents": "Autogenous regulation of the synthesis of glutamine synthetase in Klebsiella aerogenes. We isolated an F' episome of Escherichia coli carrying the glnA+ gene from K. aerogenes and an F' episome of E. coli carrying the glnA4 allele from K. aerogenes responsible for the constitutive synthesis of glutamine synthetase. Complementation tests with these episomes showed that the glnA4 mutation (leading to the constitutive synthesis of active glutamine synthetase) was in the gene identified by mutations glnA20, glnA51, and glnA5 as the structural gene for glutamine synthetase. By using these merodiploid strains we were able to show that the glnA51 mutation lead to the synthesis of a glutamine synthetase that lacked enzymatic activity but fully retained its regulatory properties. Finally, we discuss a model that explains the several phenotypes associated with mutations such as glnA4 located within the structural gene for glutamine synthetase leading to constitutive synthesis of active glutamine synthetase."}
{"id": "PMID:21159", "title": "Carbon monoxide oxidation by methanogenic bacteria.", "content": "Different species of methanogenic bacteria growing on CO(2) and H(2) were shown to remove CO added to the gas phase. Rates up to 0.2 mumol of CO depleted/min per 10 ml of culture containing approximately 7 mg of cells (wet weight) were observed. Methanobacterium thermoautotrophicum was selected for further study based on its ability to grow rapidly on a completely mineral medium. This species used CO as the sole energy source by disproportionating CO to CO(2) and CH(4) according to the following equation: 4CO + 2H(2)O --> 1CH(4) + 3CO(2). However, growth was slight, and the growth rate on CO was only 1% of that observed on H(2)/CO(2). Growth only occurred with CO concentrations in the gas phase of lower than 50%. Growth on CO agrees with the finding that cell-free extracts of M. thermoautotrophicum contained both an active factor 420 (F(420))-dependent hydrogenase (7.7 mumol/min per mg of protein at 35 degrees C) and a CO-dehydrogenating enzyme (0.2 mumol/min per mg of protein at 35 degrees C) that catalyzed the reduction of F(420) with CO. The properties of the CO-dehydrogenating enzyme are described. In addition to F(420), viologen dyes were effective electron acceptors for the enzyme. The apparent K(m) for CO was higher than 1 mM. The reaction rate increased with increasing pH and displayed an inflection point at pH 6.7. The temperature dependence of the reaction rate followed the Arrhenius equation with an activation energy (DeltaHdouble dagger) of 14.1 kcal/mol (59.0 kJ/mol). The CO dehydrogenase activity was reversibly inactivated by low concentrations of cyanide (2 muM) and was very sensitive to inactivation by oxygen. Carbon monoxide dehydrogenase of M. thermoautotrophicum exhibited several characteristic properties found for the enzyme of Clostridium pasteurianum but differed mainly in that the clostridial enzyme did not utilize F(420) as the electron acceptor.", "contents": "Carbon monoxide oxidation by methanogenic bacteria. Different species of methanogenic bacteria growing on CO(2) and H(2) were shown to remove CO added to the gas phase. Rates up to 0.2 mumol of CO depleted/min per 10 ml of culture containing approximately 7 mg of cells (wet weight) were observed. Methanobacterium thermoautotrophicum was selected for further study based on its ability to grow rapidly on a completely mineral medium. This species used CO as the sole energy source by disproportionating CO to CO(2) and CH(4) according to the following equation: 4CO + 2H(2)O --> 1CH(4) + 3CO(2). However, growth was slight, and the growth rate on CO was only 1% of that observed on H(2)/CO(2). Growth only occurred with CO concentrations in the gas phase of lower than 50%. Growth on CO agrees with the finding that cell-free extracts of M. thermoautotrophicum contained both an active factor 420 (F(420))-dependent hydrogenase (7.7 mumol/min per mg of protein at 35 degrees C) and a CO-dehydrogenating enzyme (0.2 mumol/min per mg of protein at 35 degrees C) that catalyzed the reduction of F(420) with CO. The properties of the CO-dehydrogenating enzyme are described. In addition to F(420), viologen dyes were effective electron acceptors for the enzyme. The apparent K(m) for CO was higher than 1 mM. The reaction rate increased with increasing pH and displayed an inflection point at pH 6.7. The temperature dependence of the reaction rate followed the Arrhenius equation with an activation energy (DeltaHdouble dagger) of 14.1 kcal/mol (59.0 kJ/mol). The CO dehydrogenase activity was reversibly inactivated by low concentrations of cyanide (2 muM) and was very sensitive to inactivation by oxygen. Carbon monoxide dehydrogenase of M. thermoautotrophicum exhibited several characteristic properties found for the enzyme of Clostridium pasteurianum but differed mainly in that the clostridial enzyme did not utilize F(420) as the electron acceptor."}
{"id": "PMID:21160", "title": "Efficient sporulation of yeast in media buffered near pH6.", "content": "Diploid cells of Saccharomyces cerevisiae underwent meiosis and sporulation when placed in 1% potassium acetate sporulation medium. In unbuffered sporulation medium the pH rose very rapidly, reaching pH 8.4 after 2 h of sporulation. Under these conditions, the uptake of radioactive adenine and lysine was extremely limited, and ascus formation was insensitive to inhibitors such as 5-fluorouracil and canavanine. By using several different buffers, we showed that an increase in the pH of sporulation media was not necessary for sporulation to occur. Spore viability and the kinetics of ascus and prototroph formation were normal for cells sporulated in several types of media buffered as low as pH 5.5. Incubation of sporulating cells below pH 6.5 did cause separation of small but viable buds from their mother cells. With sporulating cells buffered below pH 6.5, the incorporation of radioactive adenine and lysine was greatly enhanced and cells became sensitive to inhibition by 5-fluorouracil and canavanine.", "contents": "Efficient sporulation of yeast in media buffered near pH6. Diploid cells of Saccharomyces cerevisiae underwent meiosis and sporulation when placed in 1% potassium acetate sporulation medium. In unbuffered sporulation medium the pH rose very rapidly, reaching pH 8.4 after 2 h of sporulation. Under these conditions, the uptake of radioactive adenine and lysine was extremely limited, and ascus formation was insensitive to inhibitors such as 5-fluorouracil and canavanine. By using several different buffers, we showed that an increase in the pH of sporulation media was not necessary for sporulation to occur. Spore viability and the kinetics of ascus and prototroph formation were normal for cells sporulated in several types of media buffered as low as pH 5.5. Incubation of sporulating cells below pH 6.5 did cause separation of small but viable buds from their mother cells. With sporulating cells buffered below pH 6.5, the incorporation of radioactive adenine and lysine was greatly enhanced and cells became sensitive to inhibition by 5-fluorouracil and canavanine."}
{"id": "PMID:21161", "title": "Deoxyribonucleic acid synthesis in permeabilized spheroplasts of Saccharomyces cerevisiae.", "content": "Osmotically shocked spheroplasts from Saccharomyces cerevisiae incorporated deoxynucleoside triphosphates specifically into double-stranded nuclear and mitochondrial deoxyribonucleic acid (DNA). Results with this in vitro system for cells with and without mitochondrial DNA were compared. Strains lacking mitochondrial DNA were used to study nuclear DNA replication. With a temperature-sensitive mutant defective in DNA replication in vivo, DNA synthesis in vitro was temperature sensitive as well. The product of synthesis with all strains after very short labeling times consisted principally of short fragments that sedimented at approximately 4S in alkali; with longer pulse times or a chase with unlabeled nucleotides, they grew to a more heterogenous size, with an average of 6 to 8S and a maximum of 15S. There was little, if any, integration of these DNA fragments into the high-molecular-weight nuclear DNA. Analysis by CsCl density gradient centrifugation after incorporation of bromodeoxyuridine triphosphate showed that most of the product consisted of chains containing both preexisting and newly synthesized material, but there was also a small fraction (ca. 20%) in which the strands were fully synthesized in vitro. (32)P-label transfer (\"nearest-neighbor\") experiments demonstrated that at least a part of the material synthesized in vitro contained ribonucleic acid-DNA junctions. DNA pulse-labeled in vivo in a mutant capable of taking up thymidine 5'-monophosphate, sedimented in alkali at 4S, as in the case of the in vitro experiments.", "contents": "Deoxyribonucleic acid synthesis in permeabilized spheroplasts of Saccharomyces cerevisiae. Osmotically shocked spheroplasts from Saccharomyces cerevisiae incorporated deoxynucleoside triphosphates specifically into double-stranded nuclear and mitochondrial deoxyribonucleic acid (DNA). Results with this in vitro system for cells with and without mitochondrial DNA were compared. Strains lacking mitochondrial DNA were used to study nuclear DNA replication. With a temperature-sensitive mutant defective in DNA replication in vivo, DNA synthesis in vitro was temperature sensitive as well. The product of synthesis with all strains after very short labeling times consisted principally of short fragments that sedimented at approximately 4S in alkali; with longer pulse times or a chase with unlabeled nucleotides, they grew to a more heterogenous size, with an average of 6 to 8S and a maximum of 15S. There was little, if any, integration of these DNA fragments into the high-molecular-weight nuclear DNA. Analysis by CsCl density gradient centrifugation after incorporation of bromodeoxyuridine triphosphate showed that most of the product consisted of chains containing both preexisting and newly synthesized material, but there was also a small fraction (ca. 20%) in which the strands were fully synthesized in vitro. (32)P-label transfer (\"nearest-neighbor\") experiments demonstrated that at least a part of the material synthesized in vitro contained ribonucleic acid-DNA junctions. DNA pulse-labeled in vivo in a mutant capable of taking up thymidine 5'-monophosphate, sedimented in alkali at 4S, as in the case of the in vitro experiments."}
{"id": "PMID:21162", "title": "Location and properties of glucose dehydrogenase in sporulating cells and spores of Bacillus subtilis.", "content": "Late during sporulation, Bacillus subtilis produces glucose dehydrogenase (GlcDH; EC 1.1.1.47), which can react with D-glucose or 2-deoxy-D-glucose and can use nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) as a cofactor. This enzyme is found mainly in the forespore compartment and is present in spores; it is probably made exclusively in the forespore. The properties of GlcDH were determined both in crude cell extracts and after purification. The enzyme is stable at pH 6.5 but labile at pH 8 or higher; the pH optimum of enzyme activity is 8. After inactivation at pH 8, the activity can be recovered in crude extracts, but not in solutions of the purified enzyme, by incubation with 3 M KCl and 5 mM NAD or NADP. As determined by gel filtration, enzymatically active GlcDH has a molecular weight of about 115,000 (if the enzyme is assumed to be globular). GlcDH is distinct from a catabolite-repressible inositol dehydrogenase (EC 1.1.1.18), which can also react with D-glucose, requires specifically NAD as a cofactor, and has an electrophoretic mobility different from that of GlcDH.", "contents": "Location and properties of glucose dehydrogenase in sporulating cells and spores of Bacillus subtilis. Late during sporulation, Bacillus subtilis produces glucose dehydrogenase (GlcDH; EC 1.1.1.47), which can react with D-glucose or 2-deoxy-D-glucose and can use nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) as a cofactor. This enzyme is found mainly in the forespore compartment and is present in spores; it is probably made exclusively in the forespore. The properties of GlcDH were determined both in crude cell extracts and after purification. The enzyme is stable at pH 6.5 but labile at pH 8 or higher; the pH optimum of enzyme activity is 8. After inactivation at pH 8, the activity can be recovered in crude extracts, but not in solutions of the purified enzyme, by incubation with 3 M KCl and 5 mM NAD or NADP. As determined by gel filtration, enzymatically active GlcDH has a molecular weight of about 115,000 (if the enzyme is assumed to be globular). GlcDH is distinct from a catabolite-repressible inositol dehydrogenase (EC 1.1.1.18), which can also react with D-glucose, requires specifically NAD as a cofactor, and has an electrophoretic mobility different from that of GlcDH."}
{"id": "PMID:21163", "title": "Purification and characterization of the membrane-bound ferrochelatase from Spirillum itersonii.", "content": "The membrane-bound enzyme ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) was purified from isolated membrane fragments of Spirillum itersonii approximately 490-fold. Purification was achieved by solubilization with chaotropic salts followed by ammonium sulfate fractionation, diethylaminoethyl-cellulose chromatography, and gel filtration on Sephadex G-200. The purified enzyme has an apparent minimum molecular weight of approximately 50,000, as determined by gel filtration in the presence of 0.1% Brij 35 and 1 mM dithiothreitol but forms high-molecular-weight aggregates in the absence of detergent. Purified ferrochelatase is strongly stimulated in the presence of copper. The apparent Km for Fe2+ is 20 micrometer in the absence of copper and 9.5 micrometer in the presence of 20 micrometer CuCl2. The apparent Km for protoporphyrin is 50 micrometer, and it is unaltered by copper. Ferrochelatase has a single pH optimum of 7.50, and it is inhibited 50% by 20 micrometer heme. Certain divalent cations and sulfhydryl reagents also inhibit the enzyme.", "contents": "Purification and characterization of the membrane-bound ferrochelatase from Spirillum itersonii. The membrane-bound enzyme ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) was purified from isolated membrane fragments of Spirillum itersonii approximately 490-fold. Purification was achieved by solubilization with chaotropic salts followed by ammonium sulfate fractionation, diethylaminoethyl-cellulose chromatography, and gel filtration on Sephadex G-200. The purified enzyme has an apparent minimum molecular weight of approximately 50,000, as determined by gel filtration in the presence of 0.1% Brij 35 and 1 mM dithiothreitol but forms high-molecular-weight aggregates in the absence of detergent. Purified ferrochelatase is strongly stimulated in the presence of copper. The apparent Km for Fe2+ is 20 micrometer in the absence of copper and 9.5 micrometer in the presence of 20 micrometer CuCl2. The apparent Km for protoporphyrin is 50 micrometer, and it is unaltered by copper. Ferrochelatase has a single pH optimum of 7.50, and it is inhibited 50% by 20 micrometer heme. Certain divalent cations and sulfhydryl reagents also inhibit the enzyme."}
{"id": "PMID:21164", "title": "Regulation of superoxide dismutase synthesis in Escherichia coli: glucose effect.", "content": "Growth of Escherichia coli, based upon the fermentation of glucose, is associated with a low intracellular level of superoxide dismutase. Exhaustion of glucose, or depression of the pH due to accumulation of organic acids, causes these organisms to then obtain energy from the oxidative degradation of other substances present in a rich medium. This shift in metabolism is associated with a marked increase in the rate of synthesis of superoxide dismutase. Depression of the synthesis of superoxide dismutase by glucose is not due to catabolite repression since it is not eliminated by cyclic adenosine 3',5'-monophosphate and since alpha-methyl glucoside does not mimic the effect of glucose. Moreover, glucose itself no longer depresses superoxide dismutase synthesis when the pH has fallen low enough to cause a shift to a non-fermentative metabolism. It appears likely that superoxide dismutase is controlled directly or indirectly by the intracellular level of O2- and that glucose depressed the level of this enzyme because glucose metabolism is not associated with as rapid a production of O2- as is the metabolsim of many other substances. In accord with this view is the observation that paraquat, which can increase the rate of production of O2- by redox cycling, caused a rapid and marked increase in superoxide dismutase.", "contents": "Regulation of superoxide dismutase synthesis in Escherichia coli: glucose effect. Growth of Escherichia coli, based upon the fermentation of glucose, is associated with a low intracellular level of superoxide dismutase. Exhaustion of glucose, or depression of the pH due to accumulation of organic acids, causes these organisms to then obtain energy from the oxidative degradation of other substances present in a rich medium. This shift in metabolism is associated with a marked increase in the rate of synthesis of superoxide dismutase. Depression of the synthesis of superoxide dismutase by glucose is not due to catabolite repression since it is not eliminated by cyclic adenosine 3',5'-monophosphate and since alpha-methyl glucoside does not mimic the effect of glucose. Moreover, glucose itself no longer depresses superoxide dismutase synthesis when the pH has fallen low enough to cause a shift to a non-fermentative metabolism. It appears likely that superoxide dismutase is controlled directly or indirectly by the intracellular level of O2- and that glucose depressed the level of this enzyme because glucose metabolism is not associated with as rapid a production of O2- as is the metabolsim of many other substances. In accord with this view is the observation that paraquat, which can increase the rate of production of O2- by redox cycling, caused a rapid and marked increase in superoxide dismutase."}
{"id": "PMID:21165", "title": "Obligatory coupling between proton entry and the synthesis of adenosine 5'-triphosphate in Streptococcus lactis.", "content": "Proton influx was measured after imposition of an electrochemical potential difference for protons (delta muH+) across the cell membrane of the anaerobe, Streptococcus lactis. As delta muH+ was increased, there was an approximately parallel increase in proton entry, until delta muH+ attained 175 to 200 mV. At this point, a new pathway became available for proton entry, allowing an abrupt increase in both the rate and extent of H+ influx. This gated response depended upon the value of delta muH+ itself, and not upon the value of either the membrane potential or the pH gradient. For delta muH+ above 175 to 200 mV, elevated proton entry occurred only in cells having a functional membrane-bound Ca2+-stimulated, Mg2+stimulated adenosine 5'-triphosphatase (EC 3.6.1.3). When present, elevated proton entry coincided with the appearance of net synthesis of adenosine 5'-triphosphate catalyzed by this adenosine 5'-triphosphatase. These observations demonstrate that membrane-bound adenosine 5'-triphosphatase catalyzes an obligatory coupling between the inward movement of protons and synthesis of adenosine 5'-triphosphate.", "contents": "Obligatory coupling between proton entry and the synthesis of adenosine 5'-triphosphate in Streptococcus lactis. Proton influx was measured after imposition of an electrochemical potential difference for protons (delta muH+) across the cell membrane of the anaerobe, Streptococcus lactis. As delta muH+ was increased, there was an approximately parallel increase in proton entry, until delta muH+ attained 175 to 200 mV. At this point, a new pathway became available for proton entry, allowing an abrupt increase in both the rate and extent of H+ influx. This gated response depended upon the value of delta muH+ itself, and not upon the value of either the membrane potential or the pH gradient. For delta muH+ above 175 to 200 mV, elevated proton entry occurred only in cells having a functional membrane-bound Ca2+-stimulated, Mg2+stimulated adenosine 5'-triphosphatase (EC 3.6.1.3). When present, elevated proton entry coincided with the appearance of net synthesis of adenosine 5'-triphosphate catalyzed by this adenosine 5'-triphosphatase. These observations demonstrate that membrane-bound adenosine 5'-triphosphatase catalyzes an obligatory coupling between the inward movement of protons and synthesis of adenosine 5'-triphosphate."}
{"id": "PMID:21166", "title": "Transformation in pneumococcus: existence and properties of a complex involving donor deoxyribonucleate single strands in eclipse.", "content": "Donor deoxyribonucleic acid (DNA) single strands exist in a complex during the eclipse phase in pneumococcal transformation. This eclipse complex exhibited specific physical properties distinct from those of both pure DNA single strands and native DNA. These included a lower affinity for diethylaminoethyl-cellulose and hydroxylapatite than that of single-strand DNA, faster sedimentation than the DNA chains that it contains, and a buoyant density in Cs2SO4 lower than that of native DNA. The complex was dissociated by treatments with sodium dodecyl sulfate, NaOH, guanidine-hydrochloride, chloroform, and proteinase K but was insensitive to ribonuclease.", "contents": "Transformation in pneumococcus: existence and properties of a complex involving donor deoxyribonucleate single strands in eclipse. Donor deoxyribonucleic acid (DNA) single strands exist in a complex during the eclipse phase in pneumococcal transformation. This eclipse complex exhibited specific physical properties distinct from those of both pure DNA single strands and native DNA. These included a lower affinity for diethylaminoethyl-cellulose and hydroxylapatite than that of single-strand DNA, faster sedimentation than the DNA chains that it contains, and a buoyant density in Cs2SO4 lower than that of native DNA. The complex was dissociated by treatments with sodium dodecyl sulfate, NaOH, guanidine-hydrochloride, chloroform, and proteinase K but was insensitive to ribonuclease."}
{"id": "PMID:21167", "title": "Nitrogen and ammonia assimilation in the cyanobacteria: purification of glutamine synthetase from Anabaena sp. strain CA.", "content": "Glutamine synthetase was purified from the cyanobacterium Anabaena sp. strain CA, a newly isolated marine organism. This organism grows rapidly under nitrogen-fixing conditions and therefore is ideally suited for studies concerning cyanobacterial nitrogen metabolism. Studies were conducted to optimize the production of glutamine synthetase by Anabaena CA. The highest specific activities were obtained from cells grown in the presence of atmospheric N(2) or KNO(3) (13 mM); when NH(4)Cl was used as the nitrogen source, the specific activity was reduced by approximately 40%. Furthermore, through the use of a whole-cell gamma-glutamylhydroxamate transferase assay, it was found that the maximum number of enzyme units is obtained in the late logarithmic stage of growth. Glutamine synthetase purification requires only three steps and results in a preparation that is electrophoretically homogeneous. The transferase specific activity (units per milligram of protein) of the purified enzyme is 78, whereas the biosynthetic specific activity is 2.2. The molecular weight of the native protein was found to be approximately 590,000, and the subunit molecular weight was determined to be about 50,000. Thus, this cyanobacterial enzyme closely resembles the enzyme obtained from other procaryotic sources, at least with regard to size. The purification of glutamine synthetase from Anabaena CA should stimulate a more detailed study of this enzyme and its role in cyanobacterial nitrogen metabolism.", "contents": "Nitrogen and ammonia assimilation in the cyanobacteria: purification of glutamine synthetase from Anabaena sp. strain CA. Glutamine synthetase was purified from the cyanobacterium Anabaena sp. strain CA, a newly isolated marine organism. This organism grows rapidly under nitrogen-fixing conditions and therefore is ideally suited for studies concerning cyanobacterial nitrogen metabolism. Studies were conducted to optimize the production of glutamine synthetase by Anabaena CA. The highest specific activities were obtained from cells grown in the presence of atmospheric N(2) or KNO(3) (13 mM); when NH(4)Cl was used as the nitrogen source, the specific activity was reduced by approximately 40%. Furthermore, through the use of a whole-cell gamma-glutamylhydroxamate transferase assay, it was found that the maximum number of enzyme units is obtained in the late logarithmic stage of growth. Glutamine synthetase purification requires only three steps and results in a preparation that is electrophoretically homogeneous. The transferase specific activity (units per milligram of protein) of the purified enzyme is 78, whereas the biosynthetic specific activity is 2.2. The molecular weight of the native protein was found to be approximately 590,000, and the subunit molecular weight was determined to be about 50,000. Thus, this cyanobacterial enzyme closely resembles the enzyme obtained from other procaryotic sources, at least with regard to size. The purification of glutamine synthetase from Anabaena CA should stimulate a more detailed study of this enzyme and its role in cyanobacterial nitrogen metabolism."}
{"id": "PMID:21168", "title": "Secretion of lipids induced by inhibition of peptidoglycan synthesis in streptococci.", "content": "Inhibition of peptidoglycan synthesis causes an immediate and massive secretion of both newly synthesized and \"old\" lipids from several species of bacteria, including streptococci, Staphylococcus epidermidis, and Bacillus subtilis. Lipid secretion occurs in the absence of detectable bacterial lysis. This novel phenomenon was examined in more detail in three strains of streptococci: S. sanguis (group H), S. pyogenes (group A), And S. pneumoniae. The secretion of lipids is specifically induced by inhibitors of peptidoglycan synthesis; it is not caused by inhibitors of protein, ribonucleic acid, or deoxyribonucleic acid synthesis. The occurrence appears to be reversible since penicillin-induced secretion comes to a halt upon the timely addition of penicillinase, correlating with resumption of culture growth. All cellular lipids are secreted in essentially the same proportions as those found in the drug treated bacteria. It is suggested that continued peptidoglycan synthesis may be essential for the integration and retention of lipid material in the plasma membrane.", "contents": "Secretion of lipids induced by inhibition of peptidoglycan synthesis in streptococci. Inhibition of peptidoglycan synthesis causes an immediate and massive secretion of both newly synthesized and \"old\" lipids from several species of bacteria, including streptococci, Staphylococcus epidermidis, and Bacillus subtilis. Lipid secretion occurs in the absence of detectable bacterial lysis. This novel phenomenon was examined in more detail in three strains of streptococci: S. sanguis (group H), S. pyogenes (group A), And S. pneumoniae. The secretion of lipids is specifically induced by inhibitors of peptidoglycan synthesis; it is not caused by inhibitors of protein, ribonucleic acid, or deoxyribonucleic acid synthesis. The occurrence appears to be reversible since penicillin-induced secretion comes to a halt upon the timely addition of penicillinase, correlating with resumption of culture growth. All cellular lipids are secreted in essentially the same proportions as those found in the drug treated bacteria. It is suggested that continued peptidoglycan synthesis may be essential for the integration and retention of lipid material in the plasma membrane."}
{"id": "PMID:21170", "title": "Isolation and characterization of NADP+-specific isocitrate dehydrogenase from the pupa of Bombyx mori.", "content": "NADP+-specific isocitrate dehydrogenase was found in several tissues of the pupa of the silkworm, Bombyx mori. This enzyme was highly purified from the whole bodies of pupae. This is the first isolation of the enzyme from insect materials. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis. The reaction catalyzed by the purified enzyme was readily reversible. The pH optimum for the forward reaction (reduction of NADP+) was 7.8, and that for the reverse reaction (oxidation of NADPH) was 6.6. The enzyme had a molecular weight of 86,000 and was found to be composed of two identical subunits, which have a molecular weight of 44,000. The activity of the enzyme in the forward reaction was slightly inhibited by citrate, oxaloacetate, alpha-ketoglutarate, and others. Citrate stabilized the activity over a wide pH region.", "contents": "Isolation and characterization of NADP+-specific isocitrate dehydrogenase from the pupa of Bombyx mori. NADP+-specific isocitrate dehydrogenase was found in several tissues of the pupa of the silkworm, Bombyx mori. This enzyme was highly purified from the whole bodies of pupae. This is the first isolation of the enzyme from insect materials. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis. The reaction catalyzed by the purified enzyme was readily reversible. The pH optimum for the forward reaction (reduction of NADP+) was 7.8, and that for the reverse reaction (oxidation of NADPH) was 6.6. The enzyme had a molecular weight of 86,000 and was found to be composed of two identical subunits, which have a molecular weight of 44,000. The activity of the enzyme in the forward reaction was slightly inhibited by citrate, oxaloacetate, alpha-ketoglutarate, and others. Citrate stabilized the activity over a wide pH region."}
{"id": "PMID:21171", "title": "Stimulatory effect of n-alkanes on CTP: Cholinephosphate cytidyltransferase activity in rat liver microsomal membranes in vitro.", "content": "To assess the effect of alteration of membrane structure on the enzymic activities related to phospholipid synthesis in microsomal membrane, the effects of several organic solvents have been studied in an in vitro system, in which the cytoplasmic extract prepared from rat liver incorporated [14C]choline or [14C]CDP-choline into phosphatidycholine (lecithin). The optimum conditions for the incorporation were determined. Among several organic solvents examined, n-alkanes such as n-hexane, n-octane, and n-tetradecane stimulated the incorporation. It was shown that n-alkanes stimulated one of three enzymic steps of lecithin biosynthesis from choline; that is, the formulation of CDP-choline catalyzed by CTP: cholinephosphate cytidyltransferase [EC 2.7.7.15], an enzyme on the microsomal membrane. It was further shown that the same enzyme was also stimulated by preincubation of microsomes in the absence of substrate. It is suggested that alteration of the lipid environment of the microsomal membrane induced by n-alkanes caused activation of this enzymic step.", "contents": "Stimulatory effect of n-alkanes on CTP: Cholinephosphate cytidyltransferase activity in rat liver microsomal membranes in vitro. To assess the effect of alteration of membrane structure on the enzymic activities related to phospholipid synthesis in microsomal membrane, the effects of several organic solvents have been studied in an in vitro system, in which the cytoplasmic extract prepared from rat liver incorporated [14C]choline or [14C]CDP-choline into phosphatidycholine (lecithin). The optimum conditions for the incorporation were determined. Among several organic solvents examined, n-alkanes such as n-hexane, n-octane, and n-tetradecane stimulated the incorporation. It was shown that n-alkanes stimulated one of three enzymic steps of lecithin biosynthesis from choline; that is, the formulation of CDP-choline catalyzed by CTP: cholinephosphate cytidyltransferase [EC 2.7.7.15], an enzyme on the microsomal membrane. It was further shown that the same enzyme was also stimulated by preincubation of microsomes in the absence of substrate. It is suggested that alteration of the lipid environment of the microsomal membrane induced by n-alkanes caused activation of this enzymic step."}
{"id": "PMID:21172", "title": "H+ translocation in lysozyme-treated cells of the blue-green alga Plectonema boryanum. Difference between isotonically and hypotonically treated preparations and effects of divalent cations.", "content": "Lysozyme-treated cells of a blue-green alga, Plectonema boryanum, had an internal pH of 7.3+/-0.2 under isotonic and hypotonic conditions. This value was similar to that of untreated cells. The CCCP-induced biphasic H+ change seen in the isotonic cells was not observed in the hypotonically treated cells. The biphasic time course remained in the hypotonic preparation if CaCl2 or MgCl2 was added prior to the osmotic shock. It is suggested that the cells have two compartments of H+ concentration. The outer region may be more acidic than the inner region. A light-induced H+ efflux was observed under isotonic conditions and an influx of H+ under hypotonic conditions. The H+ influx was not observed when lysozyme-treated cells were incubated with CaCl2 or MgCl2 prior to the hypotonic treatment. Two types of effects of divalent cations, one on the rigidity of the outer membrane and another on the permeability characteristics of the inner photosynthetic membrane, are indicated. Rearrangement of the photosynthetic membranes and an apparent inversion of the H+ pump by hypotonic shock are also suggested.", "contents": "H+ translocation in lysozyme-treated cells of the blue-green alga Plectonema boryanum. Difference between isotonically and hypotonically treated preparations and effects of divalent cations. Lysozyme-treated cells of a blue-green alga, Plectonema boryanum, had an internal pH of 7.3+/-0.2 under isotonic and hypotonic conditions. This value was similar to that of untreated cells. The CCCP-induced biphasic H+ change seen in the isotonic cells was not observed in the hypotonically treated cells. The biphasic time course remained in the hypotonic preparation if CaCl2 or MgCl2 was added prior to the osmotic shock. It is suggested that the cells have two compartments of H+ concentration. The outer region may be more acidic than the inner region. A light-induced H+ efflux was observed under isotonic conditions and an influx of H+ under hypotonic conditions. The H+ influx was not observed when lysozyme-treated cells were incubated with CaCl2 or MgCl2 prior to the hypotonic treatment. Two types of effects of divalent cations, one on the rigidity of the outer membrane and another on the permeability characteristics of the inner photosynthetic membrane, are indicated. Rearrangement of the photosynthetic membranes and an apparent inversion of the H+ pump by hypotonic shock are also suggested."}
{"id": "PMID:21173", "title": "Deoxyribonuclease A, a novel deoxyribonuclease highly active toward Polydeoxyadenylic acid and polythymidylic acid from Achatina fulica.", "content": "Two novel deoxyribonucleases, termed DNases A and A', have been purified from the hepatopancreas of Achatina fulica (agate snail). DNases A and A' were obtained in 3.6 % and 7.7% yields by acetate buffer extraction and successive chromatography on hydroxyapatite, phosphocellulose and poly(A)-Sepharose. The two DNases are highly active toward poly(dA) and at a salt concentration of 0.15 m and pH 5.0 exhibit 10-fold higher hydrolyzing activities toward poly(dA) than toward calf thymus denature DNA. The enzymes also act considerably on poly(dT) at pH 4.0, but do not appreciably digest other synthetic homopolymers such as poly(dC), poly(dG) and poly(A). The limit products obtained by exhaustive digestion of poly(dA) with DNases A and A' are 98% and 99% acid-soluble and consist of oligonucleotides with an average chain length of about 5 nucleotides containing barely detectable dimers and trimers, respectively. These fragments have terminal 5'-hydroxyl and 3'-phosphate groups. The mode of action appears to be endonucleolytic. Both enzymes have the same pH optimum of 5.0 for poly(dA-hydrolyzing activity. Ionic strength is critical for the maximum activity.", "contents": "Deoxyribonuclease A, a novel deoxyribonuclease highly active toward Polydeoxyadenylic acid and polythymidylic acid from Achatina fulica. Two novel deoxyribonucleases, termed DNases A and A', have been purified from the hepatopancreas of Achatina fulica (agate snail). DNases A and A' were obtained in 3.6 % and 7.7% yields by acetate buffer extraction and successive chromatography on hydroxyapatite, phosphocellulose and poly(A)-Sepharose. The two DNases are highly active toward poly(dA) and at a salt concentration of 0.15 m and pH 5.0 exhibit 10-fold higher hydrolyzing activities toward poly(dA) than toward calf thymus denature DNA. The enzymes also act considerably on poly(dT) at pH 4.0, but do not appreciably digest other synthetic homopolymers such as poly(dC), poly(dG) and poly(A). The limit products obtained by exhaustive digestion of poly(dA) with DNases A and A' are 98% and 99% acid-soluble and consist of oligonucleotides with an average chain length of about 5 nucleotides containing barely detectable dimers and trimers, respectively. These fragments have terminal 5'-hydroxyl and 3'-phosphate groups. The mode of action appears to be endonucleolytic. Both enzymes have the same pH optimum of 5.0 for poly(dA-hydrolyzing activity. Ionic strength is critical for the maximum activity."}
{"id": "PMID:21175", "title": "Acetyl-CoA-dependent elongation of fatty acids in Mycobacterium smegmatis.", "content": "An enzyme system of Mycobacterium smegmatis catalyzing the elongation of medium-chain fatty acids with acetyl-CoA was obtained free from de novo fatty acid synthetase by ammonium sulfate fractionation. The system was resolved by gel filtration and DEAE-cellulose chromatography into three fractions, all of which were required for reconstitution of the elongation activity. The three fractions were highly purified enoyl-CoA hydratase, highly purified 3-hydroxyacyl-CoA dehydrogenase, and a fraction containing both enoyl-CoA reductase and thiolase. The reconstituted system was avidin-insenstive, required NADH as a sole hydrogen donor, and was sensitive to pCMB, but not to N-ethylmaleimide or monoiodoacetate. Decanoyl-CoA and octanoyl-CoA were the best primers for the elongation system. When decanoyl-CoA was used as the primer, the major product was found to be a lauroyl derivative (probably lauroyl-CoA). Evidence was obtained suggesting that acyl-CoA dehydrogenase, catalyzing the first step of beta-oxidation, was not functional in the elongation system.", "contents": "Acetyl-CoA-dependent elongation of fatty acids in Mycobacterium smegmatis. An enzyme system of Mycobacterium smegmatis catalyzing the elongation of medium-chain fatty acids with acetyl-CoA was obtained free from de novo fatty acid synthetase by ammonium sulfate fractionation. The system was resolved by gel filtration and DEAE-cellulose chromatography into three fractions, all of which were required for reconstitution of the elongation activity. The three fractions were highly purified enoyl-CoA hydratase, highly purified 3-hydroxyacyl-CoA dehydrogenase, and a fraction containing both enoyl-CoA reductase and thiolase. The reconstituted system was avidin-insenstive, required NADH as a sole hydrogen donor, and was sensitive to pCMB, but not to N-ethylmaleimide or monoiodoacetate. Decanoyl-CoA and octanoyl-CoA were the best primers for the elongation system. When decanoyl-CoA was used as the primer, the major product was found to be a lauroyl derivative (probably lauroyl-CoA). Evidence was obtained suggesting that acyl-CoA dehydrogenase, catalyzing the first step of beta-oxidation, was not functional in the elongation system."}
{"id": "PMID:21178", "title": "Isolation and characterization of malic enzyme from the pupa of Bombyx mori.", "content": "Malic enzyme, which requires NADP+ as a coenzyme, was isolated and purified  from pupae of the silkworm, Bombyx mori. The purified enzyme appeared homogeneous and had a molecular weight of 195,000 on polyacrylamide gel electrophoresis. The optimum pH for the oxidative decarboxylation of malate, measured in terms of the increase of NADPH (MH activity) and CO2 (MC activity), was pH 7.5, while that for the decarboxylation of oxaloacetate measured in terms of the increase of CO2 (OC activity) was pH 4.6. Several differences between MH  and OC activity were investigated.", "contents": "Isolation and characterization of malic enzyme from the pupa of Bombyx mori. Malic enzyme, which requires NADP+ as a coenzyme, was isolated and purified  from pupae of the silkworm, Bombyx mori. The purified enzyme appeared homogeneous and had a molecular weight of 195,000 on polyacrylamide gel electrophoresis. The optimum pH for the oxidative decarboxylation of malate, measured in terms of the increase of NADPH (MH activity) and CO2 (MC activity), was pH 7.5, while that for the decarboxylation of oxaloacetate measured in terms of the increase of CO2 (OC activity) was pH 4.6. Several differences between MH  and OC activity were investigated."}
{"id": "PMID:21179", "title": "The structure and function of ribonuclease T1 XXIV. Preparation and properties of a stable water-insoluble polyacrylamide derivative of ribonuclease T1.", "content": "Ribonuclease T1 [EC 3.1.4.8] was coupled to a water-insoluble cross-linked polyacrylamide (Enzacryl AH) by the acid azide method. The immobilized enzyme exhibited about 45% and 77% of the original activity toward yeast RNA and 2', 3-cyclic GMP, respectively, as substrates. Although the specific activity was lowered by the coupling, the immobilized enzyme was found to be far more stable to heat and extremes of PH than the native enzyme. The immobilized enzyme was active toward RNA even above pH 9 (at 37 degree C) or above 60 degree C (at pH 7.5), where the native enzyme was inactive. The immobilized enzyme retained much of its activity as assayed at 37 degree C after incubation in the range of pH 1 to 10 at 37 degree C, or after heating at 100 degree C (at pH 7.5) under conditions where the native enzyme was inactivated to a considerable extent. The enzyme derivative could be repeatedly recovered and reused without much loss of activity. The active site glutamic acid-58 in the immobilized enzyme appeared to be nearly as reactive with iodoacetate as that in the native enzyme.", "contents": "The structure and function of ribonuclease T1 XXIV. Preparation and properties of a stable water-insoluble polyacrylamide derivative of ribonuclease T1. Ribonuclease T1 [EC 3.1.4.8] was coupled to a water-insoluble cross-linked polyacrylamide (Enzacryl AH) by the acid azide method. The immobilized enzyme exhibited about 45% and 77% of the original activity toward yeast RNA and 2', 3-cyclic GMP, respectively, as substrates. Although the specific activity was lowered by the coupling, the immobilized enzyme was found to be far more stable to heat and extremes of PH than the native enzyme. The immobilized enzyme was active toward RNA even above pH 9 (at 37 degree C) or above 60 degree C (at pH 7.5), where the native enzyme was inactive. The immobilized enzyme retained much of its activity as assayed at 37 degree C after incubation in the range of pH 1 to 10 at 37 degree C, or after heating at 100 degree C (at pH 7.5) under conditions where the native enzyme was inactivated to a considerable extent. The enzyme derivative could be repeatedly recovered and reused without much loss of activity. The active site glutamic acid-58 in the immobilized enzyme appeared to be nearly as reactive with iodoacetate as that in the native enzyme."}
{"id": "PMID:21180", "title": "Reactivity of ferrous myoglobin at low pH.", "content": "The rates of reaction of myoglobin with carbon monoxide at low pH are reported. The pH versus rate profile of these kinetics resembles that found for heme model compounds, revealing an increase in combination rate at low pH. These facts suggest that CO binding by myoglobin changes from a mechanism of \"direct ligant association\" at pH 5 to a mechanism, similar to that proposed for heme model compounds, which assumes a tetracoordinated intermediate as a result of the protonation of the proximal imidazole.", "contents": "Reactivity of ferrous myoglobin at low pH. The rates of reaction of myoglobin with carbon monoxide at low pH are reported. The pH versus rate profile of these kinetics resembles that found for heme model compounds, revealing an increase in combination rate at low pH. These facts suggest that CO binding by myoglobin changes from a mechanism of \"direct ligant association\" at pH 5 to a mechanism, similar to that proposed for heme model compounds, which assumes a tetracoordinated intermediate as a result of the protonation of the proximal imidazole."}
{"id": "PMID:21182", "title": "Endogenous activating factor for guanylate cyclase in synaptosomal-soluble fraction of rat brain.", "content": "When the crude mitochondrial fraction of rat brain was homogenized with distilled water and centrifuged, most of guanylate cyclase activity was detected in the soluble fraction. The total guanylate cyclase activity recovered in the soluble fraction was 5- to 8-fold higher than that of the crude mitochondrial fraction. The greater recovery of guanylate cyclase activity was found to be due to a release of an endogenous activating factor for guanylate cyclase. The activating factor was partially purified by acid extraction followed by a gel filtration and ion exchange resin columns. The factor was a dialyzable small molecule. The molecular weight was estimated to be between 300 and 600 by a Sephadex G-15 column and Diaflo ultrafilter membranes. It was stable in dilute acids, but labile in alkaline solution. It was readily soluble in water, but insoluble in organic solvents. Treatment with various enzymes, so far as tested, failed to abolish the activity. The activating factor stimulated the initial velocity of the reaction. It altered neither the Km value for GTP nor the dependency of the enzyme on divalent metals. The activation by the factor was due to an increase in the Vmax of the reaction. The activation was prevented by lysolecithin, Lubrol PX, hydroxylamine, methylhydroxylamine, or hemoglobin.", "contents": "Endogenous activating factor for guanylate cyclase in synaptosomal-soluble fraction of rat brain. When the crude mitochondrial fraction of rat brain was homogenized with distilled water and centrifuged, most of guanylate cyclase activity was detected in the soluble fraction. The total guanylate cyclase activity recovered in the soluble fraction was 5- to 8-fold higher than that of the crude mitochondrial fraction. The greater recovery of guanylate cyclase activity was found to be due to a release of an endogenous activating factor for guanylate cyclase. The activating factor was partially purified by acid extraction followed by a gel filtration and ion exchange resin columns. The factor was a dialyzable small molecule. The molecular weight was estimated to be between 300 and 600 by a Sephadex G-15 column and Diaflo ultrafilter membranes. It was stable in dilute acids, but labile in alkaline solution. It was readily soluble in water, but insoluble in organic solvents. Treatment with various enzymes, so far as tested, failed to abolish the activity. The activating factor stimulated the initial velocity of the reaction. It altered neither the Km value for GTP nor the dependency of the enzyme on divalent metals. The activation by the factor was due to an increase in the Vmax of the reaction. The activation was prevented by lysolecithin, Lubrol PX, hydroxylamine, methylhydroxylamine, or hemoglobin."}
{"id": "PMID:21183", "title": "Studies of the beta-galactoside transporter in inverted membrane vesicles of Escherichia coli. I. Symmetrical facilitated diffusion and proton gradient-coupled transport.", "content": "Facilitated diffusion of [14C]lactose into inverted membrane vesicles of Escherichia coli was measured using HgCl2 as a stopping reagent and polylysine to flocculate the vesicles for filtration. Equilibration of lactose between the internal and external volumes required expression of the y gene of the lac operon and was inhibited by thiodigalactoside or by prior incubation with N-ethylmaleimde or HgCl2. The initial rate of uptake was saturable, with a Kt of 0.95 mM. Counterflow of [14C]lactose was demonstrated in either direction. ATP hydrolysis or respiration drove the efflux of internal lactose. The effect of ATP required addition of F1 coupling factor (ATPase) from E. coli when lactose transport was studied in F1-deficient inverted vesicles. Accumulation of lactose against a concentration gradient was achieved by forming an artificial electrochemical proton gradient consisting of a membrane potential negative inside or a pH gradient basic inside. Addition of ATP inhibited this proton driven uptake showing that it occurred in inverted vesicles. It was concluded that the lactose-proton co-transport protein (M protein) is qualitatively symmetrical with respect to the facilitated diffusion of lactose and the coupling of proton and lactose transport.", "contents": "Studies of the beta-galactoside transporter in inverted membrane vesicles of Escherichia coli. I. Symmetrical facilitated diffusion and proton gradient-coupled transport. Facilitated diffusion of [14C]lactose into inverted membrane vesicles of Escherichia coli was measured using HgCl2 as a stopping reagent and polylysine to flocculate the vesicles for filtration. Equilibration of lactose between the internal and external volumes required expression of the y gene of the lac operon and was inhibited by thiodigalactoside or by prior incubation with N-ethylmaleimde or HgCl2. The initial rate of uptake was saturable, with a Kt of 0.95 mM. Counterflow of [14C]lactose was demonstrated in either direction. ATP hydrolysis or respiration drove the efflux of internal lactose. The effect of ATP required addition of F1 coupling factor (ATPase) from E. coli when lactose transport was studied in F1-deficient inverted vesicles. Accumulation of lactose against a concentration gradient was achieved by forming an artificial electrochemical proton gradient consisting of a membrane potential negative inside or a pH gradient basic inside. Addition of ATP inhibited this proton driven uptake showing that it occurred in inverted vesicles. It was concluded that the lactose-proton co-transport protein (M protein) is qualitatively symmetrical with respect to the facilitated diffusion of lactose and the coupling of proton and lactose transport."}
{"id": "PMID:21184", "title": "Nucleus-dependent regulation of tyrosine aminotransferase degradation in hepatoma tissue culture cells.", "content": "Upon removal of the  nucleus from rat hepatoma tissue culture cells, levels of the enzyme tyrosine aminotransferase no longer change in response to withdrawal of glucocorticoids. The rate of tyrosine aminotransferase degradation is drastically reduced in rat hepatoma tissue culture cytoplasts leading to stabilization of pre-existing levels of tyrosine aminotransferase. Moreover, the rate of synthesis of the enzyme in cytoplasts is very low near that observed in uninduced whole cells. These effects of enucleation occur very rapidly and appear to be specific for tyrosine aminotransferase and a small number of other unstable hepatoma proteins. A nuclear effect is thus directly involved in the control of tyrosine aminotransferase degradation and synthesis.", "contents": "Nucleus-dependent regulation of tyrosine aminotransferase degradation in hepatoma tissue culture cells. Upon removal of the  nucleus from rat hepatoma tissue culture cells, levels of the enzyme tyrosine aminotransferase no longer change in response to withdrawal of glucocorticoids. The rate of tyrosine aminotransferase degradation is drastically reduced in rat hepatoma tissue culture cytoplasts leading to stabilization of pre-existing levels of tyrosine aminotransferase. Moreover, the rate of synthesis of the enzyme in cytoplasts is very low near that observed in uninduced whole cells. These effects of enucleation occur very rapidly and appear to be specific for tyrosine aminotransferase and a small number of other unstable hepatoma proteins. A nuclear effect is thus directly involved in the control of tyrosine aminotransferase degradation and synthesis."}
{"id": "PMID:21188", "title": "Stabilization of adenylate energy charge and its relation to human sperm motility.", "content": "The adenylate energy charge of human ejaculated spermatozoa was studied when the sperm motility was perturbed by varying pH, prolonged incubation, and caffeine. Between pH 8 and 9, which was optimal for the sperm motility, the energy charge was in the physiological range of 0.8 to 0.9. Above pH 9, the mobility, ATP content, and adenine nucleotide pool declined rapidly but the energy charge was maintained slightly below 0.8. Below pH 8, the motility also dropped drastically, but the ATP, nucleotide pool, and energy charge fell only slightly. Prolonged incubations of the spermatozoa decreased the motility, ATP, and nucleotide pool. However, the energy charge would remain above 0.6. Caffeine stimulation of the motility caused a rapid fall of ATP and the reduction of the physiological energy charge by 0.2 unit, unless glucose was added. Imidazole which reduced the caffeine-stimulated motility did not alter the physiological energy charge of the spermatozoa. The study showed that the spermatozoa could maintain the energy charge above 0.6 under stress.", "contents": "Stabilization of adenylate energy charge and its relation to human sperm motility. The adenylate energy charge of human ejaculated spermatozoa was studied when the sperm motility was perturbed by varying pH, prolonged incubation, and caffeine. Between pH 8 and 9, which was optimal for the sperm motility, the energy charge was in the physiological range of 0.8 to 0.9. Above pH 9, the mobility, ATP content, and adenine nucleotide pool declined rapidly but the energy charge was maintained slightly below 0.8. Below pH 8, the motility also dropped drastically, but the ATP, nucleotide pool, and energy charge fell only slightly. Prolonged incubations of the spermatozoa decreased the motility, ATP, and nucleotide pool. However, the energy charge would remain above 0.6. Caffeine stimulation of the motility caused a rapid fall of ATP and the reduction of the physiological energy charge by 0.2 unit, unless glucose was added. Imidazole which reduced the caffeine-stimulated motility did not alter the physiological energy charge of the spermatozoa. The study showed that the spermatozoa could maintain the energy charge above 0.6 under stress."}
{"id": "PMID:21189", "title": "Hydrogen exchange study of membrane-bound rhodopsin. I. Protein structure.", "content": "Structural parameters of rhodopsin in disc membrane preparations from frog and cattle were studied by hydrogen exchange methods. The method measures the exchange of protein amide hydrogens with water and can distinguish protons which are internally bonded from those which are hydrogen-bonded to water. The results show that about 70% of rhodopsin's peptide group protons are exposed to water. The identification of these groups as free peptides was made initially on the usual basis of the identity of their exchange rate with the well characterized free peptide rate; other experiments specifically excluded contributions from lipids, protein side chains, adventitious mucopolysaccharides, and intradisc water. In contrast to rhodopsin, other proteins generally have only 20 to 40% free peptide groups. Apparently rhodopsin has some unusual structural feature. Our results together with available information on rhodopsin suggest that a considerable length of its polypeptide chain is arranged at the surface of a channel of water penetrating into the membrane. Physicochemical considerations indicate that such a channel would have to be quite wide, 10 to 12 A or more, to explain the hydrogen exchange results.", "contents": "Hydrogen exchange study of membrane-bound rhodopsin. I. Protein structure. Structural parameters of rhodopsin in disc membrane preparations from frog and cattle were studied by hydrogen exchange methods. The method measures the exchange of protein amide hydrogens with water and can distinguish protons which are internally bonded from those which are hydrogen-bonded to water. The results show that about 70% of rhodopsin's peptide group protons are exposed to water. The identification of these groups as free peptides was made initially on the usual basis of the identity of their exchange rate with the well characterized free peptide rate; other experiments specifically excluded contributions from lipids, protein side chains, adventitious mucopolysaccharides, and intradisc water. In contrast to rhodopsin, other proteins generally have only 20 to 40% free peptide groups. Apparently rhodopsin has some unusual structural feature. Our results together with available information on rhodopsin suggest that a considerable length of its polypeptide chain is arranged at the surface of a channel of water penetrating into the membrane. Physicochemical considerations indicate that such a channel would have to be quite wide, 10 to 12 A or more, to explain the hydrogen exchange results."}
{"id": "PMID:21190", "title": "Hydrogen exchange study of membrane-bound rhodopsin. II. Light-induced protein structure change.", "content": "Hydrogen exchange studies of rhodopsin in disc membranes demonstrated that photolysis induces changes in the protein itself. Two different altered forms were detected. A late photointermediate in the bleaching sequence, which can be identified with metarhodopsin II, displays accelerated exchange. Subsequently, at the stage of fully bleached opsin, exchange becomes even slower than in rhodopsin. These changes involve only a small fraction of the protein's internally hydrogen-bonded peptide groups. The unusually large fraction of exposed peptide hydrogens observed previously for rhodopsin is unaltered in the photolyzed forms.", "contents": "Hydrogen exchange study of membrane-bound rhodopsin. II. Light-induced protein structure change. Hydrogen exchange studies of rhodopsin in disc membranes demonstrated that photolysis induces changes in the protein itself. Two different altered forms were detected. A late photointermediate in the bleaching sequence, which can be identified with metarhodopsin II, displays accelerated exchange. Subsequently, at the stage of fully bleached opsin, exchange becomes even slower than in rhodopsin. These changes involve only a small fraction of the protein's internally hydrogen-bonded peptide groups. The unusually large fraction of exposed peptide hydrogens observed previously for rhodopsin is unaltered in the photolyzed forms."}
{"id": "PMID:21191", "title": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. IV. The COOH-terminal 669 residues of the peptide chain; comparison with other glutamate dehydrogenases.", "content": "A sequence is presented for the COOH-terminal 669 residues of the NAD-specific glutamate dehydrogenase of Neurospora crassa. Comparison of this sequence with those of the vertebrate glutamate dehydrogenases of chicken and bovine liver and with the NADP-specific enzyme of Neurospora shows some similarities in sequences around residues previously identified as important for the function of these enzymes. These are: (a) the reactive lysine residue of low pK in the NADP and the vertebrate enzymes; (b) the tyrosine residue of the NADP enzyme that is readily nitrated by tetranitromethane with inactivation, a residue protected by NADP or by NMN; and (c) the arginine residue of the NADP-enzyme that is reactive with 1,2-cyclohexanedione with inactivation. Despite these similarities, comparison of the sequence of the NAD-enzyme with those of the other glutamate dehydrogenases of known sequences revealed relatively little overall homology as determined by computer analysis.", "contents": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. IV. The COOH-terminal 669 residues of the peptide chain; comparison with other glutamate dehydrogenases. A sequence is presented for the COOH-terminal 669 residues of the NAD-specific glutamate dehydrogenase of Neurospora crassa. Comparison of this sequence with those of the vertebrate glutamate dehydrogenases of chicken and bovine liver and with the NADP-specific enzyme of Neurospora shows some similarities in sequences around residues previously identified as important for the function of these enzymes. These are: (a) the reactive lysine residue of low pK in the NADP and the vertebrate enzymes; (b) the tyrosine residue of the NADP enzyme that is readily nitrated by tetranitromethane with inactivation, a residue protected by NADP or by NMN; and (c) the arginine residue of the NADP-enzyme that is reactive with 1,2-cyclohexanedione with inactivation. Despite these similarities, comparison of the sequence of the NAD-enzyme with those of the other glutamate dehydrogenases of known sequences revealed relatively little overall homology as determined by computer analysis."}
{"id": "PMID:21192", "title": "Membrane isolation on polylysine-coated beads. Plasma membrane from HeLa cells.", "content": "HeLa cell plasma membranes have been purified after binding cells to polylysine-coated polyacrylamide beads. Cell attachment to beads and membrane recovery were maximal in a sucrose-acetate buffer, pH 5.0, at 25 degrees C. Measurements of ouabain-sensitive NaK-adenosine triphosphatase, membrane-bound 125I-wheat germ agglutinin, and chemical analyses showed that membranes on beads were of comparable or greater purity than membranes isolated by conventional methods. Because the isolation procedure is rapid (approximately 2.5 h), and produces membranes whose protoplasmic surfaces are fully exposed, it should be a useful supplement to standard isolation techniques.", "contents": "Membrane isolation on polylysine-coated beads. Plasma membrane from HeLa cells. HeLa cell plasma membranes have been purified after binding cells to polylysine-coated polyacrylamide beads. Cell attachment to beads and membrane recovery were maximal in a sucrose-acetate buffer, pH 5.0, at 25 degrees C. Measurements of ouabain-sensitive NaK-adenosine triphosphatase, membrane-bound 125I-wheat germ agglutinin, and chemical analyses showed that membranes on beads were of comparable or greater purity than membranes isolated by conventional methods. Because the isolation procedure is rapid (approximately 2.5 h), and produces membranes whose protoplasmic surfaces are fully exposed, it should be a useful supplement to standard isolation techniques."}
{"id": "PMID:21193", "title": "Patterns of plasminogen activator production in cultured normal embryonic cells.", "content": "Cultured normal low-passage embryo fibroblasts, from a number of species, and two untransformed clones of a Balb/3T3 line elaborate increasing amounts of plasminogen activator (PA) as they approach confluence; the low-passage cells then lose this PA activity after reaching confluence, while the 3T3 cells retain it indefinitely. Even at their peaks, however, the PA activities of the low-passage cells remain well below those of the corresponding virally or spontaneously transformed cells. The PA increases in normal cells are probably a result of PA production rather than of adsorption of secreted PA to the cell surface, or of changes in cell-associated protease inhibitors. The elaboration of PA by normal cells is dependent upon their metabolic activity, such that the level of serum supplementation and the growth phase of the culture directly influence the level of cell-associated PA observed. In addition, there may be a component of serum which exerts a negative control on PA production and which is not an acid-labile protease inhibitor.", "contents": "Patterns of plasminogen activator production in cultured normal embryonic cells. Cultured normal low-passage embryo fibroblasts, from a number of species, and two untransformed clones of a Balb/3T3 line elaborate increasing amounts of plasminogen activator (PA) as they approach confluence; the low-passage cells then lose this PA activity after reaching confluence, while the 3T3 cells retain it indefinitely. Even at their peaks, however, the PA activities of the low-passage cells remain well below those of the corresponding virally or spontaneously transformed cells. The PA increases in normal cells are probably a result of PA production rather than of adsorption of secreted PA to the cell surface, or of changes in cell-associated protease inhibitors. The elaboration of PA by normal cells is dependent upon their metabolic activity, such that the level of serum supplementation and the growth phase of the culture directly influence the level of cell-associated PA observed. In addition, there may be a component of serum which exerts a negative control on PA production and which is not an acid-labile protease inhibitor."}
{"id": "PMID:21194", "title": "Complementary use of the reversed-phase and anion-exchange modes of high-pressure liquid chromatography for studies of reduced nicotinamide adenine dinucleotide.", "content": "The reversed-phase and anion-exchange modes of high-pressure liquid chromatography were used to separate breakdown products and impurities in solutions of the reduced form of nicotinamide adenine dinucleotide (NADH). The two chromatographic modes are compared for studies of NADH. Their use in following the course of acidic breakdown of NADH is described.", "contents": "Complementary use of the reversed-phase and anion-exchange modes of high-pressure liquid chromatography for studies of reduced nicotinamide adenine dinucleotide. The reversed-phase and anion-exchange modes of high-pressure liquid chromatography were used to separate breakdown products and impurities in solutions of the reduced form of nicotinamide adenine dinucleotide (NADH). The two chromatographic modes are compared for studies of NADH. Their use in following the course of acidic breakdown of NADH is described."}
{"id": "PMID:21195", "title": "Fractionation and characterization of acidic ogligosaccharides and glycopeptides from normal and pathological urines.", "content": "A general procedure is described for the isolation of urinary acidic oligosaccharides and glycopeptides resulting from catabolism of glycoproteins. This procedure has been applied to normal urine and to urine from patients with diseases of the metabolism, including mucolipidosis and fucosidosis.", "contents": "Fractionation and characterization of acidic ogligosaccharides and glycopeptides from normal and pathological urines. A general procedure is described for the isolation of urinary acidic oligosaccharides and glycopeptides resulting from catabolism of glycoproteins. This procedure has been applied to normal urine and to urine from patients with diseases of the metabolism, including mucolipidosis and fucosidosis."}
{"id": "PMID:21196", "title": "Bromothymol blue and carbohydrate-sensitive plating media.", "content": "A new plating medium using bromothymol blue (BTB) indicator is described and compared with eosin-methylene blue (EMB), MacConkey, and Endo media. These media were tested with L-arabinose by plating fermenting and nonfermenting mutant strains of Escherichia coli. The minimum concentrations of L-arabinose that permitted differentiation of these strains were determined. Different concentrations were required for differentiating confluent patches of cells, isolated colonies, and closely spaced or adjacent colonies. L-Arabinose, L-rhamnose, D-lactose, and D-galactose were tested with modified enteric media and with BTB medium, again to determine minimum usable concentrations. BTB media and reformulated conventional media allowed detection of acidification, aerobically, at one-fifth to one-hundredth the (1%, wt/vol) concentration of carbohydrate used in standard indicator plates.", "contents": "Bromothymol blue and carbohydrate-sensitive plating media. A new plating medium using bromothymol blue (BTB) indicator is described and compared with eosin-methylene blue (EMB), MacConkey, and Endo media. These media were tested with L-arabinose by plating fermenting and nonfermenting mutant strains of Escherichia coli. The minimum concentrations of L-arabinose that permitted differentiation of these strains were determined. Different concentrations were required for differentiating confluent patches of cells, isolated colonies, and closely spaced or adjacent colonies. L-Arabinose, L-rhamnose, D-lactose, and D-galactose were tested with modified enteric media and with BTB medium, again to determine minimum usable concentrations. BTB media and reformulated conventional media allowed detection of acidification, aerobically, at one-fifth to one-hundredth the (1%, wt/vol) concentration of carbohydrate used in standard indicator plates."}
{"id": "PMID:21197", "title": "Effect of aldosterone on the coupling between H+ transport and glucose oxidation.", "content": "The mode of action of aldosterone on the energetics of H+ transport in the turtle bladder was examined with the rate of glucose oxidation as an index of the metabolic activity of the epithelium (we show that H+ transport is not coupled to fatty acid oxidation). Within 6 h of addition of aldosterone H+, transport increased; so did glucose oxidation. The amount of H+ transport per mole of 14CO2 produced from glucose oxidation was 15.6 eq-mol-1 in the control hemi-bladder, while in the aldosterone-treated bladder it was 13.6, delta = 2.0+/-4.0 (n = 6). However, in bladders exposed to aldosterone for 20 h, the relation of transport to glucose oxidation was significantly altered: control 10.8, aldosterone 16.4, delta = 4.5+/-2.5, P less than 0.02, n = 7. The slope of H+ transport on the applied electrochemical gradient was steeper during both short- and long-term incubations. However, the maximum gradient necessary to nullify the net rate of secretion was unaltered in both experiments. Evidence is presented that aldosterone does not alter the passive backflux into the cell. In five additional experiments where aldosterone produced no significant stimulation of H+ transport, no change was noted in any of the metabolic or transport characteristics measured, suggesting that the alterations discussed above are dependent on the stimulation of H+ transport by the hormone. These results, along with some thermodynamic considerations, suggest that the effect of aldosterone is primarily exerted on the transport process rather than on metabolism. Further, it appears that prolonged stimulation of transport work leads to secondary alterations in the metabolic pathways reminiscent of the changes that occur in skeletal muscles of athletes undergoing physical conditioning.", "contents": "Effect of aldosterone on the coupling between H+ transport and glucose oxidation. The mode of action of aldosterone on the energetics of H+ transport in the turtle bladder was examined with the rate of glucose oxidation as an index of the metabolic activity of the epithelium (we show that H+ transport is not coupled to fatty acid oxidation). Within 6 h of addition of aldosterone H+, transport increased; so did glucose oxidation. The amount of H+ transport per mole of 14CO2 produced from glucose oxidation was 15.6 eq-mol-1 in the control hemi-bladder, while in the aldosterone-treated bladder it was 13.6, delta = 2.0+/-4.0 (n = 6). However, in bladders exposed to aldosterone for 20 h, the relation of transport to glucose oxidation was significantly altered: control 10.8, aldosterone 16.4, delta = 4.5+/-2.5, P less than 0.02, n = 7. The slope of H+ transport on the applied electrochemical gradient was steeper during both short- and long-term incubations. However, the maximum gradient necessary to nullify the net rate of secretion was unaltered in both experiments. Evidence is presented that aldosterone does not alter the passive backflux into the cell. In five additional experiments where aldosterone produced no significant stimulation of H+ transport, no change was noted in any of the metabolic or transport characteristics measured, suggesting that the alterations discussed above are dependent on the stimulation of H+ transport by the hormone. These results, along with some thermodynamic considerations, suggest that the effect of aldosterone is primarily exerted on the transport process rather than on metabolism. Further, it appears that prolonged stimulation of transport work leads to secondary alterations in the metabolic pathways reminiscent of the changes that occur in skeletal muscles of athletes undergoing physical conditioning."}
{"id": "PMID:21198", "title": "The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog.", "content": "It has generally been thought that homeostatic mechanisms of renal origin are responsible for minimizing the alkalemia produced by chronic hypocapnia. Recent observations from this laboratory have demonstrated, however, that the decrement in [HCO(-) (3)], which \"protects\" extracellular pH in normal dogs, is simply the by-product of a nonspecific effect of Paco(2) on renal hydrogen ion secretion; chronic primary hypocapnia produces virtually the same decrement in plasma [HCO(-) (3)] in dogs with chronic HCl acidosis as in normal dogs (Delta[HCO(-) (3)]/DeltaPaco(2) = 0.5), with the result that plasma [H(+)] in animals with severe acidosis rises rather than falls during superimposed forced hyperventilation. This observation raised the possibility that the secondary hypocapnia which normally accompanies metabolic acidosis, if persistent, might induce an analogous renal response and thereby contribute to the steady-state decrement in plasma [HCO(-) (3)] observed during HCl feeding. We reasoned that if sustained secondary hypocapnia provoked the kidney to depress renal bicarbonate reabsorption, the acute salutary effect of hypocapnia on plasma acidity might be seriously undermined. To isolate the possible effects of secondary hypocapnia from those of the hydrogen ion load, per se, animals were maintained in an atmosphere of 2.6% CO(2) during an initial 8-day period of acid feeding (7 mmol/kg per day); this maneuver allowed Paco(2) to be held constant at the control level of 36 mm Hg despite the hyperventilation induced by the acidemia. Steady-state bicarbonate concentration during the period of eucapnia fell from 20.8 to 16.0 meq/liter, while [H(+)] rose from 42 to 55 neq/liter. During the second phase of the study, acid feeding was continued but CO(2) was removed from the inspired air, permitting Paco(2) to fall by 6 mm Hg. In response to this secondary hypocapnia, bicarbonate concentration fell by an additional 3.0 meq/liter to a new steady-state level of 13.0 meq/liter. This reduction in bicarbonate was of sufficient magnitude to more than offset the acute salutary effect of the hypocapnia on plasma hydrogen ion concentration; in fact, steady-state [H(+)] rose as a function of the adaptive fall in Paco(2), Delta[H(+)]/Delta Paco(2) = -0.44. That the fall in bicarbonate observed in response to chronic secondary hypocapnia was the result of the change in Paco(2) was confirmed by the observation that plasma bicarbonate returned to its eucapnic level in a subgroup of animals re-exposed to 2.6% CO(2). These data indicate that the decrement in plasma [HCO(-) (3)] seen in chronic HCl acidosis is a composite function of (a) the acid load itself and (b) the renal response to the associated hyperventilation. We conclude that this renal response is maladaptive because it clearly diminishes the degree to which plasma acidity is protected by secondary hypocapnia acutely. Moreover, under some circumstances, this maladaptation actually results in more severe acidemia than would occur in the complete absence of secondary hypocapnia.", "contents": "The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog. It has generally been thought that homeostatic mechanisms of renal origin are responsible for minimizing the alkalemia produced by chronic hypocapnia. Recent observations from this laboratory have demonstrated, however, that the decrement in [HCO(-) (3)], which \"protects\" extracellular pH in normal dogs, is simply the by-product of a nonspecific effect of Paco(2) on renal hydrogen ion secretion; chronic primary hypocapnia produces virtually the same decrement in plasma [HCO(-) (3)] in dogs with chronic HCl acidosis as in normal dogs (Delta[HCO(-) (3)]/DeltaPaco(2) = 0.5), with the result that plasma [H(+)] in animals with severe acidosis rises rather than falls during superimposed forced hyperventilation. This observation raised the possibility that the secondary hypocapnia which normally accompanies metabolic acidosis, if persistent, might induce an analogous renal response and thereby contribute to the steady-state decrement in plasma [HCO(-) (3)] observed during HCl feeding. We reasoned that if sustained secondary hypocapnia provoked the kidney to depress renal bicarbonate reabsorption, the acute salutary effect of hypocapnia on plasma acidity might be seriously undermined. To isolate the possible effects of secondary hypocapnia from those of the hydrogen ion load, per se, animals were maintained in an atmosphere of 2.6% CO(2) during an initial 8-day period of acid feeding (7 mmol/kg per day); this maneuver allowed Paco(2) to be held constant at the control level of 36 mm Hg despite the hyperventilation induced by the acidemia. Steady-state bicarbonate concentration during the period of eucapnia fell from 20.8 to 16.0 meq/liter, while [H(+)] rose from 42 to 55 neq/liter. During the second phase of the study, acid feeding was continued but CO(2) was removed from the inspired air, permitting Paco(2) to fall by 6 mm Hg. In response to this secondary hypocapnia, bicarbonate concentration fell by an additional 3.0 meq/liter to a new steady-state level of 13.0 meq/liter. This reduction in bicarbonate was of sufficient magnitude to more than offset the acute salutary effect of the hypocapnia on plasma hydrogen ion concentration; in fact, steady-state [H(+)] rose as a function of the adaptive fall in Paco(2), Delta[H(+)]/Delta Paco(2) = -0.44. That the fall in bicarbonate observed in response to chronic secondary hypocapnia was the result of the change in Paco(2) was confirmed by the observation that plasma bicarbonate returned to its eucapnic level in a subgroup of animals re-exposed to 2.6% CO(2). These data indicate that the decrement in plasma [HCO(-) (3)] seen in chronic HCl acidosis is a composite function of (a) the acid load itself and (b) the renal response to the associated hyperventilation. We conclude that this renal response is maladaptive because it clearly diminishes the degree to which plasma acidity is protected by secondary hypocapnia acutely. Moreover, under some circumstances, this maladaptation actually results in more severe acidemia than would occur in the complete absence of secondary hypocapnia."}
{"id": "PMID:21200", "title": "Solubility and heat stability of whey protein concentrates.", "content": "Rennet whey protein concentrates have excellent nutritional properties, but their use in fluid food systems is impaired by the poor heat stability of the protein. Heating whey protein concentrated solutions at neutral pH caused up to 70% losses in solubility. In the absence of added calcium, protein coagulation occurred. near the iso-electric zone whereas in the presence of .03 M calcium chloride, similar protein coagulation occurred in the whole pH range (pH 2 to pH 12). Tryptic hydrolysis of the protein increased the heat stability of whey protein concentrates considerably.", "contents": "Solubility and heat stability of whey protein concentrates. Rennet whey protein concentrates have excellent nutritional properties, but their use in fluid food systems is impaired by the poor heat stability of the protein. Heating whey protein concentrated solutions at neutral pH caused up to 70% losses in solubility. In the absence of added calcium, protein coagulation occurred. near the iso-electric zone whereas in the presence of .03 M calcium chloride, similar protein coagulation occurred in the whole pH range (pH 2 to pH 12). Tryptic hydrolysis of the protein increased the heat stability of whey protein concentrates considerably."}
{"id": "PMID:21201", "title": "Lymphocyte subpopulations of atopic children and the effect of therapy upon them.", "content": "Recent reports note decreased T cell function in association with certain atopic conditions in man. This study was performed to determine whether numbers of circulating T cells are decreased in atopic children and adolescents in comparison with nonatopic age-matched control subjects. The subjects were not selected on the basis of a particular atopic diagnosis, but relatively more had allergic rhinitis and/or asthma (52) than had atopic eczema (7). Numbers of circulating T cells were not found to be significantly different in allergic children aged 2 to 10 yr than in control subjects. Atopic children and adolescents over age 10 yr had significantly fewer T cells in relative percentages (p less than 0.05), but when absolute numbers were considered significance was lost. Atopic children aged 2 to 10 years had significantly more B cells in both relative percentages and absolute numbers than did control subjects (p less than 0.02 and p less than 0.05, respectively). When those subjects treated with corticosteroids were separated from the total atopic group, there were no significant differences between the atopic and control subjects. The effects of corticosteroids, bronchodilators, antihistamines, and immunotherapy were considered and could be shown to produce no consistent effect on lymphocyte subpopulations.", "contents": "Lymphocyte subpopulations of atopic children and the effect of therapy upon them. Recent reports note decreased T cell function in association with certain atopic conditions in man. This study was performed to determine whether numbers of circulating T cells are decreased in atopic children and adolescents in comparison with nonatopic age-matched control subjects. The subjects were not selected on the basis of a particular atopic diagnosis, but relatively more had allergic rhinitis and/or asthma (52) than had atopic eczema (7). Numbers of circulating T cells were not found to be significantly different in allergic children aged 2 to 10 yr than in control subjects. Atopic children and adolescents over age 10 yr had significantly fewer T cells in relative percentages (p less than 0.05), but when absolute numbers were considered significance was lost. Atopic children aged 2 to 10 years had significantly more B cells in both relative percentages and absolute numbers than did control subjects (p less than 0.02 and p less than 0.05, respectively). When those subjects treated with corticosteroids were separated from the total atopic group, there were no significant differences between the atopic and control subjects. The effects of corticosteroids, bronchodilators, antihistamines, and immunotherapy were considered and could be shown to produce no consistent effect on lymphocyte subpopulations."}
{"id": "PMID:21202", "title": "[Cervical mucus. III. Physiological roles].", "content": "The first part of this large review on the bibliography of cervical mucus was concerned both with the mechanism and the determinism ensuring its secretion. A second paper reviewed the present knowledge on chemical, physical ultrastructural characteristics of cervical mucus. This paper, the last part of the review, will be concerned with the different functions of the mucus ensuring synchronisation and encounter of the germ cells. From a physiological point of view, the following properties may be ascribed to the cervical secretion: - protection of sperm from the hostile environment of the vagina, and from being phagocytized along the cervical canal ; - cyclic receptivity to sperm penetration at or near ovulation and interference with entry at other periods ; - filtering effect on sperm cells; - possible intracervical sperm storage ; - supplementing the energy requirements of sperm ; - protection of the uterine cavity against bacteria.", "contents": "[Cervical mucus. III. Physiological roles]. The first part of this large review on the bibliography of cervical mucus was concerned both with the mechanism and the determinism ensuring its secretion. A second paper reviewed the present knowledge on chemical, physical ultrastructural characteristics of cervical mucus. This paper, the last part of the review, will be concerned with the different functions of the mucus ensuring synchronisation and encounter of the germ cells. From a physiological point of view, the following properties may be ascribed to the cervical secretion: - protection of sperm from the hostile environment of the vagina, and from being phagocytized along the cervical canal ; - cyclic receptivity to sperm penetration at or near ovulation and interference with entry at other periods ; - filtering effect on sperm cells; - possible intracervical sperm storage ; - supplementing the energy requirements of sperm ; - protection of the uterine cavity against bacteria."}
{"id": "PMID:21203", "title": "[Neuroleptic analgesia in the management of labor].", "content": "Neuroleptic analgesia, which is used for the major part of the conduct of labour, has the advantage of abolishing the pain of uterine contractions without altering the mother's state of consciousness. A study of the effects of droperidol together with phenoperidine on the mother and the child has been carried out. Clinical results, the parameters of the intra-uterine pressure curves and the fetal heart rates as well as of the acid base balance and the pO2 of the mother and infant during dilatation of the cervix and the two first hours of life have been monitored. The conclusion is that neuroleptic analgesia does not cause neonatal depression and can be used as a method for conducting labour so long as very strict monitoring conditions are applied.", "contents": "[Neuroleptic analgesia in the management of labor]. Neuroleptic analgesia, which is used for the major part of the conduct of labour, has the advantage of abolishing the pain of uterine contractions without altering the mother's state of consciousness. A study of the effects of droperidol together with phenoperidine on the mother and the child has been carried out. Clinical results, the parameters of the intra-uterine pressure curves and the fetal heart rates as well as of the acid base balance and the pO2 of the mother and infant during dilatation of the cervix and the two first hours of life have been monitored. The conclusion is that neuroleptic analgesia does not cause neonatal depression and can be used as a method for conducting labour so long as very strict monitoring conditions are applied."}
{"id": "PMID:21204", "title": "The supply of physicians and physicians' incomes: some projections.", "content": "This study identifies trends that will lead to a dramatic increase in the number of active physicians in the United States during the next decade. The supply of active medical doctors (MDs) and doctors of osteopathy (DOs) as well as active post-graduate MDs and DOs in the U.S. is projected to increase by approximately 50 percent in the decade ending in 1985. The number of active physicians per 100,000 population is similarly expected to increase by approximately one-third. The production of surgical specialists, in particular, appears to be excessive. In response, the average length of physician graduate training programs is anticipated to be shortened as more MD and DO graduates enter shorter, general practice residencies. The authors expect that the effects of this projected increase in the supply of physicians may relieve geographic disparities in physician distribution, rationalize the organization of medical practice, and reduce physicians' incomes relative to other professional groups and possibly in absolute terms. The projected increases in the supply of physicians will give the federal government much more flexibility and bargaining power should it choose to implement a national health insurance program with salaried physicians.", "contents": "The supply of physicians and physicians' incomes: some projections. This study identifies trends that will lead to a dramatic increase in the number of active physicians in the United States during the next decade. The supply of active medical doctors (MDs) and doctors of osteopathy (DOs) as well as active post-graduate MDs and DOs in the U.S. is projected to increase by approximately 50 percent in the decade ending in 1985. The number of active physicians per 100,000 population is similarly expected to increase by approximately one-third. The production of surgical specialists, in particular, appears to be excessive. In response, the average length of physician graduate training programs is anticipated to be shortened as more MD and DO graduates enter shorter, general practice residencies. The authors expect that the effects of this projected increase in the supply of physicians may relieve geographic disparities in physician distribution, rationalize the organization of medical practice, and reduce physicians' incomes relative to other professional groups and possibly in absolute terms. The projected increases in the supply of physicians will give the federal government much more flexibility and bargaining power should it choose to implement a national health insurance program with salaried physicians."}
{"id": "PMID:21217", "title": "Adsorption of horseradish peroxidase, ovomucoid and anti-immunoglobulin to colloidal gold for the indirect detection of concanavalin A, wheat germ agglutinin and goat anti-human immunoglobulin G on cell surfaces at the electron microscopic level: a new method, theory and application.", "content": "A method is described for the adsorption of selected macromolecules to colloidal gold which is then used as an electron dense marker for the indirect detection of specific cell surface molecules. Membrane bound concanavalin A, which binds specific sugars on horseradish peroxidase, and wheat germ agglutinin, which binds specific sugars on ovomucoid are detected indirectly with gold labeled horseradish peroxidase and ovomucoid, respectively. Goat anti-human IgM on blood lymphocytes is detected with gold labeled rabbit anti-goat IgG. In the preparation of colloidal gold labeled proteins, the problems of flocculation of colloidal gold by proteins and nonadsorption of proteins to colloidal gold, are solved through a combination of concentration of protein and pH variable adsorption isotherms, which allows one to determine the conditions for adsorption of proteins to colloidal gold. Adsorption is pH dependent, the pH conditions correlating with the isoelectric point(s) of the major protein fraction(s); adsorption is influenced by interfacial tension, solubility and by the electrical charge on the molecules. Colloidal gold is inexpensive and preparation of a useful label is rapid, reproducible and the results easily quantitated from electron micrographs.", "contents": "Adsorption of horseradish peroxidase, ovomucoid and anti-immunoglobulin to colloidal gold for the indirect detection of concanavalin A, wheat germ agglutinin and goat anti-human immunoglobulin G on cell surfaces at the electron microscopic level: a new method, theory and application. A method is described for the adsorption of selected macromolecules to colloidal gold which is then used as an electron dense marker for the indirect detection of specific cell surface molecules. Membrane bound concanavalin A, which binds specific sugars on horseradish peroxidase, and wheat germ agglutinin, which binds specific sugars on ovomucoid are detected indirectly with gold labeled horseradish peroxidase and ovomucoid, respectively. Goat anti-human IgM on blood lymphocytes is detected with gold labeled rabbit anti-goat IgG. In the preparation of colloidal gold labeled proteins, the problems of flocculation of colloidal gold by proteins and nonadsorption of proteins to colloidal gold, are solved through a combination of concentration of protein and pH variable adsorption isotherms, which allows one to determine the conditions for adsorption of proteins to colloidal gold. Adsorption is pH dependent, the pH conditions correlating with the isoelectric point(s) of the major protein fraction(s); adsorption is influenced by interfacial tension, solubility and by the electrical charge on the molecules. Colloidal gold is inexpensive and preparation of a useful label is rapid, reproducible and the results easily quantitated from electron micrographs."}
{"id": "PMID:21220", "title": "Enumeration of t rosette-forming cell population in rabbit peripheral blood using human, sheep, guinea-pig, rat, mouse and chicken red blood cells under different experimental conditions.", "content": "Attempts were made to estimate peripheral T-lymphocytes in rabbits by their ability to form rosettes with sheep, human, guinea-pig, rat, mouse and chicken RBC. The reaction was studied under different conditions of pH and temperature. The test was also carried out in the presence or absence of glutaraldehyde. With sheep RBC, lymphocytes from 2 of the 5 rabbits studied formed rosettes to the extent of 1.5% in the system containing glutaraldehyde. These results however were not reproducible when studied after a week. The RBCs from other species, under similar experimental conditions, did not give rise to rosettes. The test carried out at pH 6.8 and pH 7.2 showed up to 4 and 8% rosettes respectively with rat RBCs, while RBCs of no other species showed rosettes. When rabbit lymphocytes preincubated at 37 degrees C for 1 h were used for rosette test with guinea-pig RBC, a maximum of 14.6% rosettes were obtained. Here, again the percentage of rosettes formed in the 5 animals, over a period of one month, varied widely. The reasons for the variations of the percentage of rosettes formed are discussed.", "contents": "Enumeration of t rosette-forming cell population in rabbit peripheral blood using human, sheep, guinea-pig, rat, mouse and chicken red blood cells under different experimental conditions. Attempts were made to estimate peripheral T-lymphocytes in rabbits by their ability to form rosettes with sheep, human, guinea-pig, rat, mouse and chicken RBC. The reaction was studied under different conditions of pH and temperature. The test was also carried out in the presence or absence of glutaraldehyde. With sheep RBC, lymphocytes from 2 of the 5 rabbits studied formed rosettes to the extent of 1.5% in the system containing glutaraldehyde. These results however were not reproducible when studied after a week. The RBCs from other species, under similar experimental conditions, did not give rise to rosettes. The test carried out at pH 6.8 and pH 7.2 showed up to 4 and 8% rosettes respectively with rat RBCs, while RBCs of no other species showed rosettes. When rabbit lymphocytes preincubated at 37 degrees C for 1 h were used for rosette test with guinea-pig RBC, a maximum of 14.6% rosettes were obtained. Here, again the percentage of rosettes formed in the 5 animals, over a period of one month, varied widely. The reasons for the variations of the percentage of rosettes formed are discussed."}
{"id": "PMID:21221", "title": "[Multiple forms of NADPH-dependent glutathione reductase in serum. Studies on the NADPH-dependent glutathione-reductase in serum II. (author's transl)].", "content": "Sera with elevated activities of glutathione reductase were investigated by gel electrophoresis in agar or polyacrylamide, and by gel filtration. In both separation methods the glutathione reductase activity in individual samples was resolved, showing up to three fractions differing in rate of migration and molecular size. The fractions with the lowest and highest molecular weight, corresponded respectively to the slowest and fastest migrating bands in agar gel electrophoresis. Preincubation of the serum samples with FAD or neuraminidase had no effect on the rate of migration of the three fractions. After the addition of beta-mercaptoethanol to the serum, gel electrophoresis and gel filtration showed only the enzyme fraction with the slowest rate of migration and the lowest molecular weight (140,000). The other two fractions reappeared after removal of the thiol from the serum. Further studies on the isolated (agar gel electrophoresis) fractions showed the existence of oligomeric forms of the enzyme, which are reversibly interconvertible.", "contents": "[Multiple forms of NADPH-dependent glutathione reductase in serum. Studies on the NADPH-dependent glutathione-reductase in serum II. (author's transl)]. Sera with elevated activities of glutathione reductase were investigated by gel electrophoresis in agar or polyacrylamide, and by gel filtration. In both separation methods the glutathione reductase activity in individual samples was resolved, showing up to three fractions differing in rate of migration and molecular size. The fractions with the lowest and highest molecular weight, corresponded respectively to the slowest and fastest migrating bands in agar gel electrophoresis. Preincubation of the serum samples with FAD or neuraminidase had no effect on the rate of migration of the three fractions. After the addition of beta-mercaptoethanol to the serum, gel electrophoresis and gel filtration showed only the enzyme fraction with the slowest rate of migration and the lowest molecular weight (140,000). The other two fractions reappeared after removal of the thiol from the serum. Further studies on the isolated (agar gel electrophoresis) fractions showed the existence of oligomeric forms of the enzyme, which are reversibly interconvertible."}
{"id": "PMID:21223", "title": "Liquid and solid-state Cl- -sensitive microelectrodes. Characteristics and application to intracellular Cl- activity in Balanus photoreceptor.", "content": "When intracellular chloride activity (aiCl) was monitored with chloride-sensitive liquid ion exchanges (CLIX) microelectrodes in Balanus photoreceptors, replacement of extracellular chloride (Cl0) by methanesulfonate or glutamate was followed by a rapid but incomplete loss of aiCl. When propionate was used as the extracellular anion substitute, CLIX electrodes detected an apparent gain in aiCl, while a newly designed Ag-AgCl wire-in glass microelectrode showed a loss of aiCl under the same conditions. This discrepancy in Cl- washout when propionate replaced Cl0 is explained by the differences in selectivity of CLIX and Ag-AgCl electrodes for native intracellular anions and for the extracellular anion substitute which also replaces Cli and interferes in the determination of aiCl. Both electrodes indicate that ECl approximately Em when the cells are bathed in normal barnacle saline, and both electrodes showed the rate of Cl washout (tau approximately 5 min) to be independent of Cli when Cl0 was replaced by glutamate. Details of Ag-AgCl microelectrode construction are presented. These electrodes were tested and found to be insensitive to the organic anion substitutes used in this study. Selectivity data of CLIX electrodes for several anions of biological interest are described.", "contents": "Liquid and solid-state Cl- -sensitive microelectrodes. Characteristics and application to intracellular Cl- activity in Balanus photoreceptor. When intracellular chloride activity (aiCl) was monitored with chloride-sensitive liquid ion exchanges (CLIX) microelectrodes in Balanus photoreceptors, replacement of extracellular chloride (Cl0) by methanesulfonate or glutamate was followed by a rapid but incomplete loss of aiCl. When propionate was used as the extracellular anion substitute, CLIX electrodes detected an apparent gain in aiCl, while a newly designed Ag-AgCl wire-in glass microelectrode showed a loss of aiCl under the same conditions. This discrepancy in Cl- washout when propionate replaced Cl0 is explained by the differences in selectivity of CLIX and Ag-AgCl electrodes for native intracellular anions and for the extracellular anion substitute which also replaces Cli and interferes in the determination of aiCl. Both electrodes indicate that ECl approximately Em when the cells are bathed in normal barnacle saline, and both electrodes showed the rate of Cl washout (tau approximately 5 min) to be independent of Cli when Cl0 was replaced by glutamate. Details of Ag-AgCl microelectrode construction are presented. These electrodes were tested and found to be insensitive to the organic anion substitutes used in this study. Selectivity data of CLIX electrodes for several anions of biological interest are described."}
{"id": "PMID:21224", "title": "Exopolysaccharide production by Pseudomonas NCIB11264 grown in batch culture.", "content": "Fermentation studies using batch culture indicated that exopolysaccharide production by Pseudomonas NCIBI1264 in a chemically defined medium increased under conditions of nitrogen limitation and excess carbon substrate at pH values above 6. The polysaccharide was formed from a variety of carbon substrates and its composition was not affected by the nature of the carbohydrate source. Polysacharide formation did not increase in media containing small amounts of phosphate, and, as in secondary metabolite production, it started late in the exponential growth phase continuing maximally after growth had ceased. The efficiency of glucose conversion into exopolysaccharide was low. Colorimetric, viscometric, and total carbon estimation techniques are described for determining exopolysaccharide levels in cell-free culture supernatants.", "contents": "Exopolysaccharide production by Pseudomonas NCIB11264 grown in batch culture. Fermentation studies using batch culture indicated that exopolysaccharide production by Pseudomonas NCIBI1264 in a chemically defined medium increased under conditions of nitrogen limitation and excess carbon substrate at pH values above 6. The polysaccharide was formed from a variety of carbon substrates and its composition was not affected by the nature of the carbohydrate source. Polysacharide formation did not increase in media containing small amounts of phosphate, and, as in secondary metabolite production, it started late in the exponential growth phase continuing maximally after growth had ceased. The efficiency of glucose conversion into exopolysaccharide was low. Colorimetric, viscometric, and total carbon estimation techniques are described for determining exopolysaccharide levels in cell-free culture supernatants."}
{"id": "PMID:21225", "title": "Ribonucleic acid polymerase activity associated with purified calf rotavirus.", "content": "The presence of an RNA-dependent RNA polymerase is demonstrated in purified rotavirus particles. Optimum polymerase activity was found between 45 to 50 degrees C, at pH 8, and in the presence of 10 mM-magnesium ions. The polymerase product was highly sensitive to pancreatic RNase (97%) in low or high salt concentration. The enzyme was activated by EDTA treatment of intact particles or heat shock. The similarities between reovirus, blue-tongue virus and rotavirus polymerases are discussed.", "contents": "Ribonucleic acid polymerase activity associated with purified calf rotavirus. The presence of an RNA-dependent RNA polymerase is demonstrated in purified rotavirus particles. Optimum polymerase activity was found between 45 to 50 degrees C, at pH 8, and in the presence of 10 mM-magnesium ions. The polymerase product was highly sensitive to pancreatic RNase (97%) in low or high salt concentration. The enzyme was activated by EDTA treatment of intact particles or heat shock. The similarities between reovirus, blue-tongue virus and rotavirus polymerases are discussed."}
{"id": "PMID:21226", "title": "Varicella-zoster virus-induced DNA polymerase.", "content": "Nuclear extracts of varicella-zoster virus (VZV)-infected human embryo lung (HEL) cells were found to contain DNA polymerase activity not present in uninfected HEL cells. This enzyme was designated the VZV-induced DNA polymerase. The VZV-induced polymerase was partially separated from the cellular alpha- and beta-polymerases by fractionation of the cells and by phosphocellulose chromatography. The separated enzymes were examined for the effect of added (NH4)2SO4, activity with synthetic templates, optimal pH, and the effect of phosphonoacetic acid. The VZV-induced DNA polymerase was distinct from cellular enzymes and had the properties of a typical herpesvirus-induced DNA polymerase.", "contents": "Varicella-zoster virus-induced DNA polymerase. Nuclear extracts of varicella-zoster virus (VZV)-infected human embryo lung (HEL) cells were found to contain DNA polymerase activity not present in uninfected HEL cells. This enzyme was designated the VZV-induced DNA polymerase. The VZV-induced polymerase was partially separated from the cellular alpha- and beta-polymerases by fractionation of the cells and by phosphocellulose chromatography. The separated enzymes were examined for the effect of added (NH4)2SO4, activity with synthetic templates, optimal pH, and the effect of phosphonoacetic acid. The VZV-induced DNA polymerase was distinct from cellular enzymes and had the properties of a typical herpesvirus-induced DNA polymerase."}
{"id": "PMID:21227", "title": "[A new complex polymalformative syndrome (author's transl)].", "content": "The authors discuss the nosological position and the aetiology of a complex of malformations affecting a boy, born at the end of a 40-week pregnancy with a weight of 1420 g and height of 42.5 cm, who died at the age of 3 1/2 months. The case presented an association of an acrocephalosyndactyly, phalangeal hypoplasias with anonychia, aplasia of the abdominal muscles, a genital hypoplasia with cryptorchidism and hypospadias, patches of lipodystrophy localised on the outside of the arms, at the folds of the elbow and the popliteal fossae. The autopsy revealed a large interventricular communication, absence of common mesentery and especially important cerebral anomalies (smooth brain, absence of interhemispherical suture, disorganization of the basal ganglia). The genetic study suggested a spontaneous abortion 2 1/2 months before the birth of the patient and revealed, in the mother, the presence of bilateral clinodactylies of the fingers and a unilateral syndactyly of the big toes.", "contents": "[A new complex polymalformative syndrome (author's transl)]. The authors discuss the nosological position and the aetiology of a complex of malformations affecting a boy, born at the end of a 40-week pregnancy with a weight of 1420 g and height of 42.5 cm, who died at the age of 3 1/2 months. The case presented an association of an acrocephalosyndactyly, phalangeal hypoplasias with anonychia, aplasia of the abdominal muscles, a genital hypoplasia with cryptorchidism and hypospadias, patches of lipodystrophy localised on the outside of the arms, at the folds of the elbow and the popliteal fossae. The autopsy revealed a large interventricular communication, absence of common mesentery and especially important cerebral anomalies (smooth brain, absence of interhemispherical suture, disorganization of the basal ganglia). The genetic study suggested a spontaneous abortion 2 1/2 months before the birth of the patient and revealed, in the mother, the presence of bilateral clinodactylies of the fingers and a unilateral syndactyly of the big toes."}
{"id": "PMID:21228", "title": "Brain tyrosine level controls striatal dopamine synthesis in haloperidol-treated rats.", "content": "Animals received either haloperidol (2 mg/kg) or probenecid (200 mg/kg) in conjunction with tyrosine (100 mg/kg) or its diluent. Striatal homovanillic acid levels increased in probenecid-treated animals to the same range whether they were given tyrosine or not. In haloperidol-treated animals the levels of homovanillic acid were significantly elevated in animals receiving tyrosine. Tyrosine and homovanillic acid levels were highly correlated as determined by linear regression analysis.", "contents": "Brain tyrosine level controls striatal dopamine synthesis in haloperidol-treated rats. Animals received either haloperidol (2 mg/kg) or probenecid (200 mg/kg) in conjunction with tyrosine (100 mg/kg) or its diluent. Striatal homovanillic acid levels increased in probenecid-treated animals to the same range whether they were given tyrosine or not. In haloperidol-treated animals the levels of homovanillic acid were significantly elevated in animals receiving tyrosine. Tyrosine and homovanillic acid levels were highly correlated as determined by linear regression analysis."}
{"id": "PMID:21229", "title": "The interactions of bromocriptine and lergotrile with dopamine and alpha-adrenergic receptors.", "content": "Bromocriptine and lergotrile, which are clinically used as antiparkinsonian (AP) agents, compete for the binding of H3-dopamine, H3-apomorphine, and H3-haloperidol to striatal membrane sites. Lergotrile has a higher affinity for the H3-dopamine binding to bovine striatal membranes than bromocriptine. Lergotrile and bromocriptine are almost equipotent in competing for the binding of H3-apomorphine to rat striatal membranes, but bromocriptine is more potent in competing for the binding of H3-haloperidol than lergotrile. These results indicate that lergotrile and bromocriptine are mixed putative agonist-antagonist with respect to the postsynaptic dopamine receptors. Lergotrile and bromocriptine at higher concentrations inhibit synaptosomal tyrosine hydroxylase activity, and reverse the apomorphine elicited enzyme inhibition. Thus, these ergot alkaloids behave as mixed agonist-antagonist also with respect to the presynaptic dopamine receptors. Bromocriptine and lergotrile, as well as other tested DH-ergot alkaloids and neuroleptics, compete for the binding of the alpha-antagonist H3-WB-4101 to rat cerebral cortical membranes. The displacing potencies of the tested DH-ergot alkaloids and of the neuroleptics indicate that they have a high affinity for the alpha-adrenoreceptors in the CNS.", "contents": "The interactions of bromocriptine and lergotrile with dopamine and alpha-adrenergic receptors. Bromocriptine and lergotrile, which are clinically used as antiparkinsonian (AP) agents, compete for the binding of H3-dopamine, H3-apomorphine, and H3-haloperidol to striatal membrane sites. Lergotrile has a higher affinity for the H3-dopamine binding to bovine striatal membranes than bromocriptine. Lergotrile and bromocriptine are almost equipotent in competing for the binding of H3-apomorphine to rat striatal membranes, but bromocriptine is more potent in competing for the binding of H3-haloperidol than lergotrile. These results indicate that lergotrile and bromocriptine are mixed putative agonist-antagonist with respect to the postsynaptic dopamine receptors. Lergotrile and bromocriptine at higher concentrations inhibit synaptosomal tyrosine hydroxylase activity, and reverse the apomorphine elicited enzyme inhibition. Thus, these ergot alkaloids behave as mixed agonist-antagonist also with respect to the presynaptic dopamine receptors. Bromocriptine and lergotrile, as well as other tested DH-ergot alkaloids and neuroleptics, compete for the binding of the alpha-antagonist H3-WB-4101 to rat cerebral cortical membranes. The displacing potencies of the tested DH-ergot alkaloids and of the neuroleptics indicate that they have a high affinity for the alpha-adrenoreceptors in the CNS."}
{"id": "PMID:21230", "title": "Comparison of gamma-glutamyl transpeptidase activity in tissues of normal and dystrophic hamsters and mice.", "content": "The activity of gamma-glutamyl transpeptidase (gamma-GT), a membrane-bound enzyme, was assayed by a sensitive fluorometric method in the brain, heart, kidney, liver, skeletal muscle and serum of normal and dystrophic hamsters and mice. Normal and dystrophic hamsters were of the golden brown and BIO 14.6 line respectively. Both normal and dystrophic mice were of the C57 BL/6J -dy2j strain. Kidneys of both hamsters and mice contained the highest enzyme activity followed by the brain, skeletal muscle, liver and heart. Gamma-GT activity was elevated in dystrophic skeletal muscles but decreased in the dystrophic kidneys and sera. In the brain, heart and liver of dystrophic animals from both species enzyme activity was similar to that in normals.", "contents": "Comparison of gamma-glutamyl transpeptidase activity in tissues of normal and dystrophic hamsters and mice. The activity of gamma-glutamyl transpeptidase (gamma-GT), a membrane-bound enzyme, was assayed by a sensitive fluorometric method in the brain, heart, kidney, liver, skeletal muscle and serum of normal and dystrophic hamsters and mice. Normal and dystrophic hamsters were of the golden brown and BIO 14.6 line respectively. Both normal and dystrophic mice were of the C57 BL/6J -dy2j strain. Kidneys of both hamsters and mice contained the highest enzyme activity followed by the brain, skeletal muscle, liver and heart. Gamma-GT activity was elevated in dystrophic skeletal muscles but decreased in the dystrophic kidneys and sera. In the brain, heart and liver of dystrophic animals from both species enzyme activity was similar to that in normals."}
{"id": "PMID:21231", "title": "8alpha-hydroxyflavinmononucleotide and related compounds.", "content": "2', 3', 4'-Triacetyl-FMN has been transformed by selective radical bromination into 2', 3', 4'-triacetyl-8alpha-bromo-FMN, and the following hydrolysis of the latter has afforded 8alpha-hydroxy-FMN. The presence of the hydroxy group in the 8alpha position of 8alpha-hydroxy-FMN is confirmed by its acetylation into 2', 3'-diacetyl-8alpha-acetoxyriboflavin-4', 5'-cyclophosphate. The absorption spectra of the synthesized compounds have shown the reduction of the extinction ratios of the first and second absorption maxima in comparison with the extinction of the same maxima for 8alpha-hydroxyriboflavin. Unlike FMN, fluorescence quenching for 8alpha-hydroxy-FMN has been found.", "contents": "8alpha-hydroxyflavinmononucleotide and related compounds. 2', 3', 4'-Triacetyl-FMN has been transformed by selective radical bromination into 2', 3', 4'-triacetyl-8alpha-bromo-FMN, and the following hydrolysis of the latter has afforded 8alpha-hydroxy-FMN. The presence of the hydroxy group in the 8alpha position of 8alpha-hydroxy-FMN is confirmed by its acetylation into 2', 3'-diacetyl-8alpha-acetoxyriboflavin-4', 5'-cyclophosphate. The absorption spectra of the synthesized compounds have shown the reduction of the extinction ratios of the first and second absorption maxima in comparison with the extinction of the same maxima for 8alpha-hydroxyriboflavin. Unlike FMN, fluorescence quenching for 8alpha-hydroxy-FMN has been found."}
{"id": "PMID:21232", "title": "The presence and possible function of methylmalonyl CoA mutase and propionyl CoA carboxylase in Spirometra mansonoides.", "content": "Both spargana and adult forms of Spirometra mansonoides were shown to accumulate lactate, succinate, acetate, and propionate upon in vitro incubation. Adults differed markedly from the spargana in that quantitatively the most significant products of the former were acetate and propionate while the latter formed primarily acetate and lactate. The adults accumulated approximately 32 times more propionate than the spargana per gram of tissue. In accord with this propionate formation, propionyl CoA carboxylase and methylmalonyl CoA mutase have been found to be present in both stages of the parasite. As might be predicted, however, the activities of the carboxylase and mutase were 100-fold and 10-fold higher, respectively, in the adults as compared to the larvae. A possible physiological relationship between propionate formation and energy generation is suggested. Accordingly, inorganic 32P was incorporated into ATP upon incubation of methylmalonyl CoA with a homogenate obtained from adult S. mansonoides. Since methylmalonyl CoA mutase requires vitamin B12 coenzyme, a relationship between vitamin B12 content and propionate formation in helminths is suggested.", "contents": "The presence and possible function of methylmalonyl CoA mutase and propionyl CoA carboxylase in Spirometra mansonoides. Both spargana and adult forms of Spirometra mansonoides were shown to accumulate lactate, succinate, acetate, and propionate upon in vitro incubation. Adults differed markedly from the spargana in that quantitatively the most significant products of the former were acetate and propionate while the latter formed primarily acetate and lactate. The adults accumulated approximately 32 times more propionate than the spargana per gram of tissue. In accord with this propionate formation, propionyl CoA carboxylase and methylmalonyl CoA mutase have been found to be present in both stages of the parasite. As might be predicted, however, the activities of the carboxylase and mutase were 100-fold and 10-fold higher, respectively, in the adults as compared to the larvae. A possible physiological relationship between propionate formation and energy generation is suggested. Accordingly, inorganic 32P was incorporated into ATP upon incubation of methylmalonyl CoA with a homogenate obtained from adult S. mansonoides. Since methylmalonyl CoA mutase requires vitamin B12 coenzyme, a relationship between vitamin B12 content and propionate formation in helminths is suggested."}
{"id": "PMID:21235", "title": "A comparison of the dissolution rates of caffeine tablets in a rotating-basket with those in a Sartorius dissolution tester.", "content": "Uncoated caffeine tablets of four different hardnesses were tested for dissolution rate by the Sartorius (S.S. method) and by the rotating basket method of the U.S.P. XVIII. In both methods the dissolution rate decreased with increasing hardness, and the rate obtained with the S.S. method was always less than that by the U.S.P. method. This result cannot be explained as being due only to the difference in the volume of dissolution medium. Also it was difficult to ensure that the characteristic changes in the process of dissolution paralleled the curves obtained from a plot of % caffeine dissolved vs time. Accordingly, the dissolution rate constants were calculated from the slope of each straight line in a plot of ln W infinity/(W infinity --W) vs time.", "contents": "A comparison of the dissolution rates of caffeine tablets in a rotating-basket with those in a Sartorius dissolution tester. Uncoated caffeine tablets of four different hardnesses were tested for dissolution rate by the Sartorius (S.S. method) and by the rotating basket method of the U.S.P. XVIII. In both methods the dissolution rate decreased with increasing hardness, and the rate obtained with the S.S. method was always less than that by the U.S.P. method. This result cannot be explained as being due only to the difference in the volume of dissolution medium. Also it was difficult to ensure that the characteristic changes in the process of dissolution paralleled the curves obtained from a plot of % caffeine dissolved vs time. Accordingly, the dissolution rate constants were calculated from the slope of each straight line in a plot of ln W infinity/(W infinity --W) vs time."}
{"id": "PMID:21236", "title": "Plasma concentrations and excretion of zipeprol in man under acidic urine conditions.", "content": "Plasma concentrations of zipeprol, and the urinary excretion of it and two of its basic metabolites, compound II and compound III were examined after oral administration of zipeprol hydrochloride to man. The drug was rapidly and extensively metabolized, and the amount of unchanged drug excreted in the acidic urine varied from 1-5% of the dose; the two basic metabolites accounted for 19-38% of the dose.", "contents": "Plasma concentrations and excretion of zipeprol in man under acidic urine conditions. Plasma concentrations of zipeprol, and the urinary excretion of it and two of its basic metabolites, compound II and compound III were examined after oral administration of zipeprol hydrochloride to man. The drug was rapidly and extensively metabolized, and the amount of unchanged drug excreted in the acidic urine varied from 1-5% of the dose; the two basic metabolites accounted for 19-38% of the dose."}
{"id": "PMID:21237", "title": "The effect of age and thyroid hormones upon the ability of the chick heart to deaminate monoamines.", "content": "The effect of age and thyroid hormones upon the ability of chick heart homogenates to metabolize monoamines has been investigated. 5-Hydroxytryptamine is entirely metabolized by a monoamine oxidase (MAO) with the characteristics of MAO-A, whereas some of the tyramine and all of the benzylamine are oxidatively deaminated by a clorgyline-resistant, but semicarbazide-sensitive enzyme, with a similar subcellular distribution to that of MAO. The remainder of the tyramine deamination is brought about by MAO-A and MAO-B. The specific activities of both clorgyline-sensitive and resistant enzymes are increased by the same proportion by increase in age or by treatment with (--)-thyroxine, and decreased by 2-thiouracil. The significance of these results is discussed.", "contents": "The effect of age and thyroid hormones upon the ability of the chick heart to deaminate monoamines. The effect of age and thyroid hormones upon the ability of chick heart homogenates to metabolize monoamines has been investigated. 5-Hydroxytryptamine is entirely metabolized by a monoamine oxidase (MAO) with the characteristics of MAO-A, whereas some of the tyramine and all of the benzylamine are oxidatively deaminated by a clorgyline-resistant, but semicarbazide-sensitive enzyme, with a similar subcellular distribution to that of MAO. The remainder of the tyramine deamination is brought about by MAO-A and MAO-B. The specific activities of both clorgyline-sensitive and resistant enzymes are increased by the same proportion by increase in age or by treatment with (--)-thyroxine, and decreased by 2-thiouracil. The significance of these results is discussed."}
{"id": "PMID:21238", "title": "Evidence from agonist and antagonist studies to suggest that the beta1-adrenoceptors subserving the positive inotropic and chronotropic responses of the heart do not belong to two separate subgroups.", "content": "The positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to 17 sympathomimetic amines were examined under conditions selected to control the pharmacological environment. Each agonist was compared with (--)-isoprenaline as the reference by constructing dose-response curves. Equiactive molar concentration ratios relative to (--)-isoprenaline were calculated at the EC50 for rate and tension responses. Statistical analysis revealed that (--)-noradrenaline and (+/-)-alpha-methylnoradrenaline were tension selective whereas (+/-)-alpha-ethylisoprenaline and N-methyldopamine were rate selective relative to (--)-isoprenaline. However, no structural trends emerged. The rank order of potency varied slightly between rate and tension, but an analysis of the regression and correlation coefficients indicated respectively that the equiactive molar concentration ratios and the rank orders could be considered identical on rate and tension. Antagonism of the (--)-isoprenaline-induced rate and tension responses by acebutolol, atenolol, practolol and propranolol was assessed from the pA2 values which were almost identical for both parameters with each antagnosti. It is concluded that the beta1-adrenoceptors mediating the positive inotropic and chronotropic responses do not warrant subdivision into two separate groups.", "contents": "Evidence from agonist and antagonist studies to suggest that the beta1-adrenoceptors subserving the positive inotropic and chronotropic responses of the heart do not belong to two separate subgroups. The positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to 17 sympathomimetic amines were examined under conditions selected to control the pharmacological environment. Each agonist was compared with (--)-isoprenaline as the reference by constructing dose-response curves. Equiactive molar concentration ratios relative to (--)-isoprenaline were calculated at the EC50 for rate and tension responses. Statistical analysis revealed that (--)-noradrenaline and (+/-)-alpha-methylnoradrenaline were tension selective whereas (+/-)-alpha-ethylisoprenaline and N-methyldopamine were rate selective relative to (--)-isoprenaline. However, no structural trends emerged. The rank order of potency varied slightly between rate and tension, but an analysis of the regression and correlation coefficients indicated respectively that the equiactive molar concentration ratios and the rank orders could be considered identical on rate and tension. Antagonism of the (--)-isoprenaline-induced rate and tension responses by acebutolol, atenolol, practolol and propranolol was assessed from the pA2 values which were almost identical for both parameters with each antagnosti. It is concluded that the beta1-adrenoceptors mediating the positive inotropic and chronotropic responses do not warrant subdivision into two separate groups."}
{"id": "PMID:21239", "title": "The role of dopaminergic systems in gamma-hydroxybutyrate-induced electrocorticogram hypersynchronization in the rat.", "content": "The effects of dopaminergic agonists and antagonists on the duration of hypersynchronization induced in the electrocorticogram (ecog) by gamma-hydroxybutyrate (gamma-HB) were tested in rats. Apomorphine (0-2-8 mg kg-1), piribedil (2-5-10 mg kt-1) and haloperidol (0-5-1 mg kg-1) had no influence on the duration of the hypersynchrony. Amphetamine (1-5-6 mg kg-1) inhibited the hypersynchrony, while (3,4-dihydroxyphenylamino)-2-imidazoline (DPI; 5, but not 1, mg kg-1) prolonged its duration. The lack of effect of the dopamine receptor agonists apomorphine and piribedil, and the dopamine receptor blocker haloperidol, on the gamma-HB-induced hypersynchrony might indicate that the inhibition of the impulse flow in the nigrostriatal dopamine system by gamma-HB is not involved in the generation of the hypersynchrony. DPI is thought to be an agonist at a dopamine receptor not sensitive to apomorphine, and its facilitatory effect on gamam-HB-hypersynchrony can be interpreted in terms of a possible involvement of another dopamine system in the ecog hypersynchrony induced by gamma-HB. The antagonism of gamma-HB by amphetamine is possibly due to an indirect stimulatory effect on noradrenergic receptors.", "contents": "The role of dopaminergic systems in gamma-hydroxybutyrate-induced electrocorticogram hypersynchronization in the rat. The effects of dopaminergic agonists and antagonists on the duration of hypersynchronization induced in the electrocorticogram (ecog) by gamma-hydroxybutyrate (gamma-HB) were tested in rats. Apomorphine (0-2-8 mg kg-1), piribedil (2-5-10 mg kt-1) and haloperidol (0-5-1 mg kg-1) had no influence on the duration of the hypersynchrony. Amphetamine (1-5-6 mg kg-1) inhibited the hypersynchrony, while (3,4-dihydroxyphenylamino)-2-imidazoline (DPI; 5, but not 1, mg kg-1) prolonged its duration. The lack of effect of the dopamine receptor agonists apomorphine and piribedil, and the dopamine receptor blocker haloperidol, on the gamma-HB-induced hypersynchrony might indicate that the inhibition of the impulse flow in the nigrostriatal dopamine system by gamma-HB is not involved in the generation of the hypersynchrony. DPI is thought to be an agonist at a dopamine receptor not sensitive to apomorphine, and its facilitatory effect on gamam-HB-hypersynchrony can be interpreted in terms of a possible involvement of another dopamine system in the ecog hypersynchrony induced by gamma-HB. The antagonism of gamma-HB by amphetamine is possibly due to an indirect stimulatory effect on noradrenergic receptors."}
{"id": "PMID:21240", "title": "The central and peripheral effectiveness of two oxotremorine-antagonists determined using oxotremorine-induced tremor and salivation.", "content": "Two oxotremorine antagonists have been examined using oxotremorine as the tremor salivation inducer and the ratios between the central and peripheral nervous systems determined. Under these conditions these compounds are still more effective antagonists centrally than peripherally. Differences in distribution to the various muscarinic receptors involved is believed to be the major factor in determining this separation of central and peripheral activities.", "contents": "The central and peripheral effectiveness of two oxotremorine-antagonists determined using oxotremorine-induced tremor and salivation. Two oxotremorine antagonists have been examined using oxotremorine as the tremor salivation inducer and the ratios between the central and peripheral nervous systems determined. Under these conditions these compounds are still more effective antagonists centrally than peripherally. Differences in distribution to the various muscarinic receptors involved is believed to be the major factor in determining this separation of central and peripheral activities."}
{"id": "PMID:21241", "title": "A sex difference in the interaction between promethazine and morphine in the mouse.", "content": "The effects of promethazine on the antinociceptive and respiratory actions of morphine have been examined in the mouse. Moderate doses of promethazine (5 and 10 mg kg-1) potentiated morphine's action in male mice but inhibited it in female mice. Gonadectomy abolished the interaction between promethazine and morphine in both sexes, although the intensity and duration of morphine's activity was greatly enhanced in these mice. Replacement of oestradiol in ovariectomized mice restored morphine's activity to intact female control values. However, interactions between promethazine and morphine required progesterone, as well as oestradiol, replacement to obtain results approaching those obtained in intact female mice.", "contents": "A sex difference in the interaction between promethazine and morphine in the mouse. The effects of promethazine on the antinociceptive and respiratory actions of morphine have been examined in the mouse. Moderate doses of promethazine (5 and 10 mg kg-1) potentiated morphine's action in male mice but inhibited it in female mice. Gonadectomy abolished the interaction between promethazine and morphine in both sexes, although the intensity and duration of morphine's activity was greatly enhanced in these mice. Replacement of oestradiol in ovariectomized mice restored morphine's activity to intact female control values. However, interactions between promethazine and morphine required progesterone, as well as oestradiol, replacement to obtain results approaching those obtained in intact female mice."}
{"id": "PMID:21242", "title": "Some antagonists of dantrolene sodium on the isolated diaphragm muscle of the rat.", "content": "The effects of a number of potential antagonists of dantrolene sodium have been studied on twitches of the isolated hemidiaphragm preparation of the rat stimulated directly at a frequency of 0-1 Hz, after complete neuromuscular block produced by tubocurarine or erabutoxin a. The substances selected as possible dantrolene antagonists were uranyl ions, thiocyanate ions, adrenaline, caffeine, quazodine, quinine, 4-aminopyridine and the calcium ionophore a23187, all of which facilitate excitation-contraction coupling in one way or another. Contracture was the main feature of the response to A23187, the increase in the tension of the dantrolene-depressed twitches being very slight. All the remaining compounds increased the amplitude of the twitches, but only 4-aminopyridine, quinine, quazodine and caffeine were capable of restoring to the control amplitude twitches that had been maximally depressed by dantrolene. OF these, 4-aminopyridine and quinine were the most potent on a molar basis.", "contents": "Some antagonists of dantrolene sodium on the isolated diaphragm muscle of the rat. The effects of a number of potential antagonists of dantrolene sodium have been studied on twitches of the isolated hemidiaphragm preparation of the rat stimulated directly at a frequency of 0-1 Hz, after complete neuromuscular block produced by tubocurarine or erabutoxin a. The substances selected as possible dantrolene antagonists were uranyl ions, thiocyanate ions, adrenaline, caffeine, quazodine, quinine, 4-aminopyridine and the calcium ionophore a23187, all of which facilitate excitation-contraction coupling in one way or another. Contracture was the main feature of the response to A23187, the increase in the tension of the dantrolene-depressed twitches being very slight. All the remaining compounds increased the amplitude of the twitches, but only 4-aminopyridine, quinine, quazodine and caffeine were capable of restoring to the control amplitude twitches that had been maximally depressed by dantrolene. OF these, 4-aminopyridine and quinine were the most potent on a molar basis."}
{"id": "PMID:21254", "title": "The dissolution mechanism in a system undergoing complexation: salicylamide in caffeine solution.", "content": "The dissolution rate of compressed salicylamide discs has been measured in water and in caffeine solutions of increasing concentration at 15, 25, 37 and 45 degrees in an apparatus rotating at 48 rev min-1 or more. Dissolution rate profiles showed breaks indicative of a shift in the mechanism of dissolution from interfacial towards transport control. The shifts occurred at higher caffeine concentrations on increasing the agitation rate or temperature. The dependencies of dissolution rates on agitation rates typified the intermediate type of dissolution and Arrhenius plots indicated that interfacial and transport processes participated in salicylamide dissolution.", "contents": "The dissolution mechanism in a system undergoing complexation: salicylamide in caffeine solution. The dissolution rate of compressed salicylamide discs has been measured in water and in caffeine solutions of increasing concentration at 15, 25, 37 and 45 degrees in an apparatus rotating at 48 rev min-1 or more. Dissolution rate profiles showed breaks indicative of a shift in the mechanism of dissolution from interfacial towards transport control. The shifts occurred at higher caffeine concentrations on increasing the agitation rate or temperature. The dependencies of dissolution rates on agitation rates typified the intermediate type of dissolution and Arrhenius plots indicated that interfacial and transport processes participated in salicylamide dissolution."}
{"id": "PMID:21255", "title": "Dilute solution properties of clindamycin 2-palmitate hydrochloride.", "content": "Clindamycin 2-palmitate hydrochloride forms micelles in aqueous solution at concentrations above 2-2 X 10(-3) M. Dilution of micellar solutions of the drug to concentrations less than 2-0 X 10(-3) M produces turbid systems. Turbidity is caused by unionized drug, produced by hydrolysis of the salt, phasing out of solution at concentrations too low for micelles to be formed. Changes in specific conductivity and turbidity associated with the phasing-out process have been measured and explained in terms of the rates of the various processes involved, including demicellization and emulsion stability. The phenomenon of phasing-out, below a critical concentration in aqueous solution, is predicted to be a general one for weakly ionized surfactants where the unionized species possesses low water solubility.", "contents": "Dilute solution properties of clindamycin 2-palmitate hydrochloride. Clindamycin 2-palmitate hydrochloride forms micelles in aqueous solution at concentrations above 2-2 X 10(-3) M. Dilution of micellar solutions of the drug to concentrations less than 2-0 X 10(-3) M produces turbid systems. Turbidity is caused by unionized drug, produced by hydrolysis of the salt, phasing out of solution at concentrations too low for micelles to be formed. Changes in specific conductivity and turbidity associated with the phasing-out process have been measured and explained in terms of the rates of the various processes involved, including demicellization and emulsion stability. The phenomenon of phasing-out, below a critical concentration in aqueous solution, is predicted to be a general one for weakly ionized surfactants where the unionized species possesses low water solubility."}
{"id": "PMID:21256", "title": "Relaxations mediated by adrenergic and non-adrenergic nerves in human isolated taenia coli.", "content": "In human taenia coli electrical field stimulation after cholinergic blockade excited mainly non-adrenergic inhibitory nerves. Adrenergic relaxations during stimulation were demonstrated only with short electrical pulses at high frequencies or with ganglion stimulants. Reduction by tetrodotoxin of relaxations to indirectly acting sympathomimetics supports the histochemical finding that colonic adrenergic nerves are mainly preganglionic, and possibly synapse with non-adrenergic inhibitory nerves. When the latter undergo direct maximal stimulation, responses to adrenergic nerve excitation are masked.", "contents": "Relaxations mediated by adrenergic and non-adrenergic nerves in human isolated taenia coli. In human taenia coli electrical field stimulation after cholinergic blockade excited mainly non-adrenergic inhibitory nerves. Adrenergic relaxations during stimulation were demonstrated only with short electrical pulses at high frequencies or with ganglion stimulants. Reduction by tetrodotoxin of relaxations to indirectly acting sympathomimetics supports the histochemical finding that colonic adrenergic nerves are mainly preganglionic, and possibly synapse with non-adrenergic inhibitory nerves. When the latter undergo direct maximal stimulation, responses to adrenergic nerve excitation are masked."}
{"id": "PMID:21257", "title": "Evidence for more than one type of 5-hydroxytryptamine receptor in the human colon.", "content": "The actions of methysergide, a 5-hydroxytryptamine (5-HT) antagonist, have been examined on muscle strips taken from the circular and longitudinal layers of the human colon. Relaxations of the longitudinal muscle to 5-HT were antagonized by concentrations of methysergide known to be selective. Relaxations of the circular muscle to 5-HT were unaffected by similar concentrations of methysergide. Responses of both types of muscle to 5-HT were partially reduced by tetrodotoxin. Furthermore there was evidence for 5-HT receptors in circular colonic muscle which were unaffected either by selective concentrations of methysergide or tetrodotoxin.", "contents": "Evidence for more than one type of 5-hydroxytryptamine receptor in the human colon. The actions of methysergide, a 5-hydroxytryptamine (5-HT) antagonist, have been examined on muscle strips taken from the circular and longitudinal layers of the human colon. Relaxations of the longitudinal muscle to 5-HT were antagonized by concentrations of methysergide known to be selective. Relaxations of the circular muscle to 5-HT were unaffected by similar concentrations of methysergide. Responses of both types of muscle to 5-HT were partially reduced by tetrodotoxin. Furthermore there was evidence for 5-HT receptors in circular colonic muscle which were unaffected either by selective concentrations of methysergide or tetrodotoxin."}
{"id": "PMID:21258", "title": "Influence of pyridylisatogen tosylate on contractions produced by ATP and by purinergic stimulation in the terminal ileum of the guinea-pig.", "content": "2-2'Pyridylisatogen tosylate (PIT), which antagonizes the inhibitory action of ATP in the taenia caeci, did not antagonize the excitatory effects of exogenous ATP and of purinergic stimulation of the terminal guinea-pig ileum. PIT (0-5--2-5 muM) potentiated the ATP-induced contractions and also the contractions produced by potassium chloride, though the potentiation could not be related to the dose in every experiment. The responses to noradrenaline, adrenaline and histamine were slightly inhibited. PIT also potentiated the contractions produced by electrical stimulation of intramural purinergic nerves when either an alternate or uniform stimulation pattern was used. The present results in which the preparation is contracted by ATP are opposite to those obtained with PIT on the taenia caeci, which is relaxed by ATP. This raises a question of duality or plurality of receptors for ATP.", "contents": "Influence of pyridylisatogen tosylate on contractions produced by ATP and by purinergic stimulation in the terminal ileum of the guinea-pig. 2-2'Pyridylisatogen tosylate (PIT), which antagonizes the inhibitory action of ATP in the taenia caeci, did not antagonize the excitatory effects of exogenous ATP and of purinergic stimulation of the terminal guinea-pig ileum. PIT (0-5--2-5 muM) potentiated the ATP-induced contractions and also the contractions produced by potassium chloride, though the potentiation could not be related to the dose in every experiment. The responses to noradrenaline, adrenaline and histamine were slightly inhibited. PIT also potentiated the contractions produced by electrical stimulation of intramural purinergic nerves when either an alternate or uniform stimulation pattern was used. The present results in which the preparation is contracted by ATP are opposite to those obtained with PIT on the taenia caeci, which is relaxed by ATP. This raises a question of duality or plurality of receptors for ATP."}
{"id": "PMID:21259", "title": "Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets.", "content": "The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly 110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-Chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-HT, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings.", "contents": "Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets. The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly 110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-Chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-HT, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings."}
{"id": "PMID:21260", "title": "Analysis of the beta-receptor mediated effect on slow-contracting skeletal muscle in vitro.", "content": "Subtetanic contractions of the guinea-pig isolated soleus, a slow-contracting skeletal muscle, were evoked by transmural field-stimulation. Isoprenaline caused a dose-dependent depression of the contractions. This effect was inhibited by propranolol and H 35/25 (1-(p-tolyl-2-isopropylamino-1-propanol) but not by practolol. Similar results were obtained for terbutaline. Tazolol and H 80/62 (1-isopropylamino-3-(p-hydroxyphenoxy)-2-propanol (HCl), selective beta1-agonists, had no effect per se but inhibited the effect of terbutaline. Adrenaline, noradrenaline, and dopamine all caused a dose-dependent decrease in the force of the soleus contractions, their potencies being in that order. Tyramine did not appreciably affect the contractions nor did it inhibit the effect of terbutaline. Pretreatment with reserpine, if anything, increased the response to terbutaline. It is concluded, in conformity with previous in vivo studies, that the adrenergic receptor mediating the effect on the soleus muscle contractions is of the beta2-type. Indirect sympathomimetic effects do not contribute to the responses observed on the isolated soleus muscle.", "contents": "Analysis of the beta-receptor mediated effect on slow-contracting skeletal muscle in vitro. Subtetanic contractions of the guinea-pig isolated soleus, a slow-contracting skeletal muscle, were evoked by transmural field-stimulation. Isoprenaline caused a dose-dependent depression of the contractions. This effect was inhibited by propranolol and H 35/25 (1-(p-tolyl-2-isopropylamino-1-propanol) but not by practolol. Similar results were obtained for terbutaline. Tazolol and H 80/62 (1-isopropylamino-3-(p-hydroxyphenoxy)-2-propanol (HCl), selective beta1-agonists, had no effect per se but inhibited the effect of terbutaline. Adrenaline, noradrenaline, and dopamine all caused a dose-dependent decrease in the force of the soleus contractions, their potencies being in that order. Tyramine did not appreciably affect the contractions nor did it inhibit the effect of terbutaline. Pretreatment with reserpine, if anything, increased the response to terbutaline. It is concluded, in conformity with previous in vivo studies, that the adrenergic receptor mediating the effect on the soleus muscle contractions is of the beta2-type. Indirect sympathomimetic effects do not contribute to the responses observed on the isolated soleus muscle."}
{"id": "PMID:21261", "title": "Biochemical and pharmacological studies on amineptine (S 1694) and (+)-amphetamine in the rat.", "content": "The pharmacological activities of amineptine (S 1694) and (+)-amphetamine and their interaction with biogenic amines have been examined in rats. The locomotor activity, stereotyped behaviour and hypothermia induced by amineptine were similar to but not as marked as those produced by (+)-amphetamine, and there was little or no anorectic action. Amineptine does not modify the concentrations of brain noradrenaline or acetylcholine which are respectively reduced and increased by (+)-amphetamine. Moreover, amineptine does not affect significantly the decrease of brain noradrenaline induced by an intraventricular injection of 6-hydroxydopamine, an effect significantly antagonized by (+)-amphetamine. On the other hand, like amphetamine, amineptine significantly reduces the effect of 6-hydroxy-dopamine on brain dopamine. Both drugs increase the striatal concentrations of homovanillic acid and show a cross tolerance in this action. Therefore they could act similarly on the striatal dopaminergine system. Amineptine thus appears to be a new type of antidepressant with a brain biochemical profile differing from that of other drugs used in depressive disorders.", "contents": "Biochemical and pharmacological studies on amineptine (S 1694) and (+)-amphetamine in the rat. The pharmacological activities of amineptine (S 1694) and (+)-amphetamine and their interaction with biogenic amines have been examined in rats. The locomotor activity, stereotyped behaviour and hypothermia induced by amineptine were similar to but not as marked as those produced by (+)-amphetamine, and there was little or no anorectic action. Amineptine does not modify the concentrations of brain noradrenaline or acetylcholine which are respectively reduced and increased by (+)-amphetamine. Moreover, amineptine does not affect significantly the decrease of brain noradrenaline induced by an intraventricular injection of 6-hydroxydopamine, an effect significantly antagonized by (+)-amphetamine. On the other hand, like amphetamine, amineptine significantly reduces the effect of 6-hydroxy-dopamine on brain dopamine. Both drugs increase the striatal concentrations of homovanillic acid and show a cross tolerance in this action. Therefore they could act similarly on the striatal dopaminergine system. Amineptine thus appears to be a new type of antidepressant with a brain biochemical profile differing from that of other drugs used in depressive disorders."}
{"id": "PMID:21278", "title": "pH-stat titration of aluminum hydroxide gel.", "content": "The pH-stat titration of aluminum hydroxide gel was evaluated and was affected by pH, temperature, concentration, and ionic strength. Control of these parameters resulted in a highly sensitive and reproducible in vitro antacid test. The utility of the pH-stat test was illustrated by monitoring the aging of several carbonate-containing aluminum hydroxide gels and by comparing the antacid properties as measured by the pH-stat titration, the acid-consuming capacity, the Rossett-Rice test, and the test proposed by the food and Drug Administration Drug Evaluation Panel. The pH-stat titration  also was useful for relatively nonreactive aluminum hydroxide gels. The use of sodium fluoride as the reaction medium extended the capability of the pH-stat titration to monitor the aging of chloride-containing gels. The pH-stat titrigram was interpreted in terms of a previously published polymer model of the structure of a chloride-containing aluminum hydroxide gel. The acid reactivity of relatively nonreactive gel is believed to be due totally to the chemical neutralization of acid, because the milliequivalents of aluminum  ion appearing in solution is the same as the milliequivalents of acid neutralized throughout the ph-stat titration.", "contents": "pH-stat titration of aluminum hydroxide gel. The pH-stat titration of aluminum hydroxide gel was evaluated and was affected by pH, temperature, concentration, and ionic strength. Control of these parameters resulted in a highly sensitive and reproducible in vitro antacid test. The utility of the pH-stat test was illustrated by monitoring the aging of several carbonate-containing aluminum hydroxide gels and by comparing the antacid properties as measured by the pH-stat titration, the acid-consuming capacity, the Rossett-Rice test, and the test proposed by the food and Drug Administration Drug Evaluation Panel. The pH-stat titration  also was useful for relatively nonreactive aluminum hydroxide gels. The use of sodium fluoride as the reaction medium extended the capability of the pH-stat titration to monitor the aging of chloride-containing gels. The pH-stat titrigram was interpreted in terms of a previously published polymer model of the structure of a chloride-containing aluminum hydroxide gel. The acid reactivity of relatively nonreactive gel is believed to be due totally to the chemical neutralization of acid, because the milliequivalents of aluminum  ion appearing in solution is the same as the milliequivalents of acid neutralized throughout the ph-stat titration."}
{"id": "PMID:21279", "title": "Relationship between zero point of charge and solubility product for hydroxides of polyvalent cations.", "content": "The zero point of charge (ZPC) of slightly soluble compounds is the pH at which their particles suspended in water have zero charge. The ZPC values of slightly soluble hydroxides were compared with their solubility product in the form of its negative logarithm, pKSP, and with th pH of their suspensions in pure water, pHSP, which is a function of pKSP. The ZPC-pKSP relation was nonlinear while the ZPC-pHSP relation was linear. Either equation can used to estimate the ZPC value of a hydroxide from its solubility product. The ZPC of a given hydroxide was higher than its pHSP because polyvalent cations are more extensively adsorbed and less extensively desorbed from the particle surface than the monovalent hydroxide ion. At the pHSP, there are equivalent amounts of the cation and of the  hydroxide anion in solution, but the surface layer of the hydroxide particle contains an excess cation on an equivalent basis. This imbalance confers a positive charge to the particle. The solubility product of aluminum hydroxide, redetermined at 25 degrees by means of pH measurements, was 8 X 10(-33). Its ZPC, redetermined by microelectrophoresis, was 8.5 +/- 0.1.", "contents": "Relationship between zero point of charge and solubility product for hydroxides of polyvalent cations. The zero point of charge (ZPC) of slightly soluble compounds is the pH at which their particles suspended in water have zero charge. The ZPC values of slightly soluble hydroxides were compared with their solubility product in the form of its negative logarithm, pKSP, and with th pH of their suspensions in pure water, pHSP, which is a function of pKSP. The ZPC-pKSP relation was nonlinear while the ZPC-pHSP relation was linear. Either equation can used to estimate the ZPC value of a hydroxide from its solubility product. The ZPC of a given hydroxide was higher than its pHSP because polyvalent cations are more extensively adsorbed and less extensively desorbed from the particle surface than the monovalent hydroxide ion. At the pHSP, there are equivalent amounts of the cation and of the  hydroxide anion in solution, but the surface layer of the hydroxide particle contains an excess cation on an equivalent basis. This imbalance confers a positive charge to the particle. The solubility product of aluminum hydroxide, redetermined at 25 degrees by means of pH measurements, was 8 X 10(-33). Its ZPC, redetermined by microelectrophoresis, was 8.5 +/- 0.1."}
{"id": "PMID:21280", "title": "In vitro photodecomposition of uric acid in presence of riboflavin II.", "content": "In vitro studies on the photodecomposition of uric acid in the presence of the monosodium salt of riboflavin 5'-phosphate in buffers at various pH values, in methanol, and in human plasma are reported. The decomposition rate increased with increasing pH and was independent of solvent or buffer species. The mechanism appears to be an energy transfer process involving triplet riboflavin and single oxygen. Riboflavin-enhanced photodecomposition of uric acid occurred in vitro in hyperuricemic human plasma.", "contents": "In vitro photodecomposition of uric acid in presence of riboflavin II. In vitro studies on the photodecomposition of uric acid in the presence of the monosodium salt of riboflavin 5'-phosphate in buffers at various pH values, in methanol, and in human plasma are reported. The decomposition rate increased with increasing pH and was independent of solvent or buffer species. The mechanism appears to be an energy transfer process involving triplet riboflavin and single oxygen. Riboflavin-enhanced photodecomposition of uric acid occurred in vitro in hyperuricemic human plasma."}
{"id": "PMID:21281", "title": "Effects of adenine nucleotides on oxidation of phenothiazine tranquilizers.", "content": "The effects of adenosine diphosphate and triphosphate on the periodic  acid oxidation of the phenothiazine tranquilizing drugs were studied. The principal effect was a marked reduction in the rate of formation and decay of the drug free radical. The oxidation rates of the nucleotide free drugs seemed to be most strongly influenced by the inductive effects of substituents at the 2-position of the phenothiazine nucleus. However, the oxidation rates of the drugs in the presence of nucleotide were most strongly influenced by the substituents at the 10-position. Variations of the structure of substituents at the 10-position have only a modest effect on the electronic state of the phenothiazine nucleus. Therefore, the marked effect of structural variation in the 10-substituents in the presence of nucleotide on the periodate oxidation rate most likely is an expression of steric effects related to an interaction between drug and nucleotide.", "contents": "Effects of adenine nucleotides on oxidation of phenothiazine tranquilizers. The effects of adenosine diphosphate and triphosphate on the periodic  acid oxidation of the phenothiazine tranquilizing drugs were studied. The principal effect was a marked reduction in the rate of formation and decay of the drug free radical. The oxidation rates of the nucleotide free drugs seemed to be most strongly influenced by the inductive effects of substituents at the 2-position of the phenothiazine nucleus. However, the oxidation rates of the drugs in the presence of nucleotide were most strongly influenced by the substituents at the 10-position. Variations of the structure of substituents at the 10-position have only a modest effect on the electronic state of the phenothiazine nucleus. Therefore, the marked effect of structural variation in the 10-substituents in the presence of nucleotide on the periodate oxidation rate most likely is an expression of steric effects related to an interaction between drug and nucleotide."}
{"id": "PMID:21282", "title": "Stability of prostaglandin E1 and dinoprostone (prostaglandin E2) under strongly acidic and basic conditions.", "content": "The stability of prostaglandin E1 and dinoprostone was investigated at the extremes of the pH range (less than or equal to 3 and greater than or equal to 10) in the sequence prostaglandin E leads to prostaglandin A leads to prostaglandin B. The degradation rate is first order with hydrogen-ion and hydroxide-ion concentrations. Separation and analysis of the E prostaglandins were accomplished by TLC and UV spectrophotometry. At the lowest pH values and at elevated or low temperatures, significant amounts of 15-epiprostaglandin E were present. Apparent activation energies for the total dinoprostone loss, calculated from elevated temperature data, were 21 kcal/mole in the strongly acidic region and about 18 kcal/mole at pH 3. Corresponding studies in the alkaline  region led to a derived arrhenius activation energy of 15 kcal/mole with the appearance of significant amounts of 8-isoprostaglandin E. This difference in activation energies may reflect the different mechanisms operant at high and low pH values.", "contents": "Stability of prostaglandin E1 and dinoprostone (prostaglandin E2) under strongly acidic and basic conditions. The stability of prostaglandin E1 and dinoprostone was investigated at the extremes of the pH range (less than or equal to 3 and greater than or equal to 10) in the sequence prostaglandin E leads to prostaglandin A leads to prostaglandin B. The degradation rate is first order with hydrogen-ion and hydroxide-ion concentrations. Separation and analysis of the E prostaglandins were accomplished by TLC and UV spectrophotometry. At the lowest pH values and at elevated or low temperatures, significant amounts of 15-epiprostaglandin E were present. Apparent activation energies for the total dinoprostone loss, calculated from elevated temperature data, were 21 kcal/mole in the strongly acidic region and about 18 kcal/mole at pH 3. Corresponding studies in the alkaline  region led to a derived arrhenius activation energy of 15 kcal/mole with the appearance of significant amounts of 8-isoprostaglandin E. This difference in activation energies may reflect the different mechanisms operant at high and low pH values."}
{"id": "PMID:21283", "title": "Tetrazole analogs of phenylalanine derivatives as tyrosine hydroxylase inhibitors.", "content": "Eight new tetrazole analogs of phenylalanine derivatives in which the carboxyl group was replaced by a tetrazole ring were synthesized. At a concentration of 2.5 time 10(-5) M, each compound exhibited greater than 50% inhibition of tyrosine hydroxylase activity.", "contents": "Tetrazole analogs of phenylalanine derivatives as tyrosine hydroxylase inhibitors. Eight new tetrazole analogs of phenylalanine derivatives in which the carboxyl group was replaced by a tetrazole ring were synthesized. At a concentration of 2.5 time 10(-5) M, each compound exhibited greater than 50% inhibition of tyrosine hydroxylase activity."}
{"id": "PMID:21284", "title": "Kinetics of concomitant degradation of tetracycline to epitetracycline, anhydrotetracycline, and epianhydrotetracycline in acid phosphate solution.", "content": "The concentrations of tetracycline, epitetracycline, anhydrotetracycline, and epianhydrotetracycline in pH 1.5 phosphate solution were followed as a function of  time at four temperatures. Separation and quantification of all four species were accomplished using high-pressure liquid chromatography. Through nonlinear regression analysis, rate constants for the reversible first-order epimerization of tetracycline and anhydrotetracycline and for the first-order dehydration of tetracycline and epitetracycline were obtained. Solutions to the differential equations obtained through Laplace transforms successfully predict concentrations found experimentally. The energy of activation for each reaction  step was calculated and ranged from 15 to 27 kcal/mole. The rate constants for tetracycline and epitetracycline dehydration conform with those of earlier studies that used different experimental methods. The study shows that epimerization of tetracycline and anhydrotetracycline can take place at a low pH.", "contents": "Kinetics of concomitant degradation of tetracycline to epitetracycline, anhydrotetracycline, and epianhydrotetracycline in acid phosphate solution. The concentrations of tetracycline, epitetracycline, anhydrotetracycline, and epianhydrotetracycline in pH 1.5 phosphate solution were followed as a function of  time at four temperatures. Separation and quantification of all four species were accomplished using high-pressure liquid chromatography. Through nonlinear regression analysis, rate constants for the reversible first-order epimerization of tetracycline and anhydrotetracycline and for the first-order dehydration of tetracycline and epitetracycline were obtained. Solutions to the differential equations obtained through Laplace transforms successfully predict concentrations found experimentally. The energy of activation for each reaction  step was calculated and ranged from 15 to 27 kcal/mole. The rate constants for tetracycline and epitetracycline dehydration conform with those of earlier studies that used different experimental methods. The study shows that epimerization of tetracycline and anhydrotetracycline can take place at a low pH."}
{"id": "PMID:21285", "title": "Evidence for antral inhibition of pentagastrin from experiments using mucosal cooling.", "content": "1. The acid secretion of the fundic mucosa in Heidenhain pouches in response to pentagastrin became progressively less as the pouch mucosa was cooled. 2. When a cooled Heidenhain pouch in an animal receiving pentagastrin was warmed, acid and pepsin secretion from the main stomach was depressed. Change from warm to cool produced no obvious effect. 3. In animals receiving pentagastrin continuously, but not in those receiving histamine, lowering the temperature in an antral pouch, or the application of local anaesthetics to its mucosa, increased acid and pepsin secretion from the main stomach when the antral pouch was fully innervated. 4. This effect could readily be abolished by ganglionic and beta-adrenergic blockade, but not by bilateral vagal block in the neck, thus suggesting a sympathetically mediated inhibitory mechanism of pyloric origin. 5. The effect of indirect vagal stimulation, using 2-deoxy-D-glucose on secretion from the main stomach, was augmented by pyloric antral local anaesthesia and depressed by antral cooling.", "contents": "Evidence for antral inhibition of pentagastrin from experiments using mucosal cooling. 1. The acid secretion of the fundic mucosa in Heidenhain pouches in response to pentagastrin became progressively less as the pouch mucosa was cooled. 2. When a cooled Heidenhain pouch in an animal receiving pentagastrin was warmed, acid and pepsin secretion from the main stomach was depressed. Change from warm to cool produced no obvious effect. 3. In animals receiving pentagastrin continuously, but not in those receiving histamine, lowering the temperature in an antral pouch, or the application of local anaesthetics to its mucosa, increased acid and pepsin secretion from the main stomach when the antral pouch was fully innervated. 4. This effect could readily be abolished by ganglionic and beta-adrenergic blockade, but not by bilateral vagal block in the neck, thus suggesting a sympathetically mediated inhibitory mechanism of pyloric origin. 5. The effect of indirect vagal stimulation, using 2-deoxy-D-glucose on secretion from the main stomach, was augmented by pyloric antral local anaesthesia and depressed by antral cooling."}
{"id": "PMID:21286", "title": "Effects of neurochemicals upon a dinoflagellate photoresponse.", "content": "Photoresponsiveness by Gymnodinium splendens Lebour was monitored quantitatively by a microscope-television system. Exposure to the catecholamines DOPA and Dopamine caused a decrease in light sensitivity, while 0.01 mM norepinephine, or isoproterenol did not affect photoresponsiveness. Classical catecholamine blocking agents, dichloroisoproterenol, propranolol, and dibenzyline, and an inhibitor of DOPA synthesis, alpha-methyl-rho-tyrosine, caused an increase in sensitivity. In addition, acetylcholine and an inhibitor of acetylcholinesterase activity, eserine, caused an increase in sensitivity, while an inhibitor of acetylcholine action atropine, had the opposite effect. These experiments suggest that G. splendens may have an antagonistic catecholamine-cholinergic system which participates in regulating photosensitivity.", "contents": "Effects of neurochemicals upon a dinoflagellate photoresponse. Photoresponsiveness by Gymnodinium splendens Lebour was monitored quantitatively by a microscope-television system. Exposure to the catecholamines DOPA and Dopamine caused a decrease in light sensitivity, while 0.01 mM norepinephine, or isoproterenol did not affect photoresponsiveness. Classical catecholamine blocking agents, dichloroisoproterenol, propranolol, and dibenzyline, and an inhibitor of DOPA synthesis, alpha-methyl-rho-tyrosine, caused an increase in sensitivity. In addition, acetylcholine and an inhibitor of acetylcholinesterase activity, eserine, caused an increase in sensitivity, while an inhibitor of acetylcholine action atropine, had the opposite effect. These experiments suggest that G. splendens may have an antagonistic catecholamine-cholinergic system which participates in regulating photosensitivity."}
{"id": "PMID:21287", "title": "Toxoplasma gondii-vertebrate cell interactions. I. The influence of bicarbonate ion, CO2, pH and host cell culture age on the invasion of vertebrate cells in vitro.", "content": "A controlled-environment culture system was used to show that both physical and biologic parameters can influence the penetration of vertebrate cells by Toxoplasma gondii. The optimum bicarbonate ion concentration for the penetration of bovine embryo skeletal muscle (BESM) cells is 36.25 mM. Higher or lower bicarbonate ion concentrations are increasingly inhibitory to penetration. As CO2 increases in the range from 0.5-3.7 mM, penetration is progressively inhibited. No relationship was found between penetration and pH in the pH range of 6.949-7.765. The culture age of the BESM cells directly influenced the ability of the parasites to penetrate the cells. Older BESM cells were more refractory to penetration than younger cells.", "contents": "Toxoplasma gondii-vertebrate cell interactions. I. The influence of bicarbonate ion, CO2, pH and host cell culture age on the invasion of vertebrate cells in vitro. A controlled-environment culture system was used to show that both physical and biologic parameters can influence the penetration of vertebrate cells by Toxoplasma gondii. The optimum bicarbonate ion concentration for the penetration of bovine embryo skeletal muscle (BESM) cells is 36.25 mM. Higher or lower bicarbonate ion concentrations are increasingly inhibitory to penetration. As CO2 increases in the range from 0.5-3.7 mM, penetration is progressively inhibited. No relationship was found between penetration and pH in the pH range of 6.949-7.765. The culture age of the BESM cells directly influenced the ability of the parasites to penetrate the cells. Older BESM cells were more refractory to penetration than younger cells."}
{"id": "PMID:21288", "title": "Specific labeling of intracellular Toxoplasma gondii with uracil.", "content": "Radioactive uracil was not significantly incorporated into the nucleic acids of human fibroblast cells. Infection of these cells with Toxoplasma gondii resulted in an exponential increase in the rate of uracil incorporation that paralleled the exponential growth of the parasite. One day after infection the rate of uracil incorporation was increased 100-fold. It was established by autoradiography that all of the [3H] uracil was incorporated into the intracellular parasites. A possible explanation for this difference in ability to use uracil is our observation that the specific activity of uridine phosphorylase was 100-fold greater in partially purified parasites than in the host cell.", "contents": "Specific labeling of intracellular Toxoplasma gondii with uracil. Radioactive uracil was not significantly incorporated into the nucleic acids of human fibroblast cells. Infection of these cells with Toxoplasma gondii resulted in an exponential increase in the rate of uracil incorporation that paralleled the exponential growth of the parasite. One day after infection the rate of uracil incorporation was increased 100-fold. It was established by autoradiography that all of the [3H] uracil was incorporated into the intracellular parasites. A possible explanation for this difference in ability to use uracil is our observation that the specific activity of uridine phosphorylase was 100-fold greater in partially purified parasites than in the host cell."}
{"id": "PMID:21289", "title": "Monoamine oxidase and catechol-O-methyl transferase activity in Tetrahymena.", "content": "Tetrahymena pyriformis strain HSM was found to have monomine oxidase (MAO) and a catechol-3-methyl transferase-like (COMT) activity. As in mammalian tissues, the MAO activity is predominantly localized in the mitochondrial pellet and COMT in the cytosol. The COMT-like activity was present in amounts comparable to several mouse tissues and was inhibited by tropolone. MAO activity was much lower than in any of the mouse tissues tested, and its activity varied greatly from preparation to preparation. The substrate preference of Tetrahymena MAO was tryptamine greater than serotonin greater than dopamine, and activity increased with increasing pH from pH 6.5 to pH 7.8, as does that of mouse liver MAO. Teh Km of Tetrahymena MAO for tryptamine was approximately 4 micrometer, an order of magnitude lower than that of mouse liver MAO. Sensitivity of inhibition by MAO inhibitors was variable. In some preparations, no inhibition was observed. In others clear inhibition was obtained, harmine and clorgyline being among the most potent inhibitors.", "contents": "Monoamine oxidase and catechol-O-methyl transferase activity in Tetrahymena. Tetrahymena pyriformis strain HSM was found to have monomine oxidase (MAO) and a catechol-3-methyl transferase-like (COMT) activity. As in mammalian tissues, the MAO activity is predominantly localized in the mitochondrial pellet and COMT in the cytosol. The COMT-like activity was present in amounts comparable to several mouse tissues and was inhibited by tropolone. MAO activity was much lower than in any of the mouse tissues tested, and its activity varied greatly from preparation to preparation. The substrate preference of Tetrahymena MAO was tryptamine greater than serotonin greater than dopamine, and activity increased with increasing pH from pH 6.5 to pH 7.8, as does that of mouse liver MAO. Teh Km of Tetrahymena MAO for tryptamine was approximately 4 micrometer, an order of magnitude lower than that of mouse liver MAO. Sensitivity of inhibition by MAO inhibitors was variable. In some preparations, no inhibition was observed. In others clear inhibition was obtained, harmine and clorgyline being among the most potent inhibitors."}
{"id": "PMID:21290", "title": "Poly(ethylene oxide), a new slowing agent for protozoa.", "content": "The water-soluble, viscoelastic resin Polyox WSR 301), a poly(ethylene oxide) of high molecular weight (approximately 4 million) is introduces as a new slowing agent for protozoa. Generally, as the kinetic viscosity of the resin increased from 0.25% to 1% (w/v), the swimming velocity of Euglena gracilis, Didnium nasutum, Paramecium aurelia, Blepharisma undulans, and Prorodon platyodon decreased. The 1.0% solution had the highest viscosity and decreased velocity more effectively than 1.0% methyl cellulose and Protoslo solutions. The Polyox solutions differed from those of methyl cellulose and Protoslo by having, in addition to viscous drag, an elastic recoil that pulled the protozoa backwards when their swimming efforts stopped. The toxicity of these slowing agents was determined using 10 P. aurelia/test slide preparation. Paramecium numbers decreased in 1.0% methyl cellulose and Protoslo to nearly zero by 24 hr; in Polyox, not only were most these ciliates alive after 24 hr, but many survived for 96 hr and divisions occurred in 0.25% and 0.50% solutions.", "contents": "Poly(ethylene oxide), a new slowing agent for protozoa. The water-soluble, viscoelastic resin Polyox WSR 301), a poly(ethylene oxide) of high molecular weight (approximately 4 million) is introduces as a new slowing agent for protozoa. Generally, as the kinetic viscosity of the resin increased from 0.25% to 1% (w/v), the swimming velocity of Euglena gracilis, Didnium nasutum, Paramecium aurelia, Blepharisma undulans, and Prorodon platyodon decreased. The 1.0% solution had the highest viscosity and decreased velocity more effectively than 1.0% methyl cellulose and Protoslo solutions. The Polyox solutions differed from those of methyl cellulose and Protoslo by having, in addition to viscous drag, an elastic recoil that pulled the protozoa backwards when their swimming efforts stopped. The toxicity of these slowing agents was determined using 10 P. aurelia/test slide preparation. Paramecium numbers decreased in 1.0% methyl cellulose and Protoslo to nearly zero by 24 hr; in Polyox, not only were most these ciliates alive after 24 hr, but many survived for 96 hr and divisions occurred in 0.25% and 0.50% solutions."}
{"id": "PMID:21291", "title": "Synthesis and pharmacological activity of some N-alkyl-substituted 9alpha-ethyl-2'-hydroxy-5-methyl-6,7-benzomorphans.", "content": "A series of N-substituted 9alpha-ethyl-2'-hydroxy-5-methyl-6,7-benzomorphans was synthesized and evaluated for their narcotic analgesic and antagonistic activities. Compounds 2a and 22 were as potent as morphine in the writhing (PPQ) and hot-plate tests, while a number of compounds demonstrated antagonistic activities greater than nalorphine. Generally, the compounds in this series show activities somewhat greater than the comparable compounds in the 5,9alpha-dimethyl-6,7-benzomorphan series for analgesic effect and similar or slightly less antagonistic potency.", "contents": "Synthesis and pharmacological activity of some N-alkyl-substituted 9alpha-ethyl-2'-hydroxy-5-methyl-6,7-benzomorphans. A series of N-substituted 9alpha-ethyl-2'-hydroxy-5-methyl-6,7-benzomorphans was synthesized and evaluated for their narcotic analgesic and antagonistic activities. Compounds 2a and 22 were as potent as morphine in the writhing (PPQ) and hot-plate tests, while a number of compounds demonstrated antagonistic activities greater than nalorphine. Generally, the compounds in this series show activities somewhat greater than the comparable compounds in the 5,9alpha-dimethyl-6,7-benzomorphan series for analgesic effect and similar or slightly less antagonistic potency."}
{"id": "PMID:21292", "title": "Application of the Free-Wilson technique to structurally related series of homologues. Quantitative structure-activity relationship studies of narcotic analgetics.", "content": "A series of benzomorphans with ED50 values determined in vivo by the hot-plate method in mice is analyzed by the modified Free-Wilson method. The QSAR yields 36 substituent constants (ai) with contributions to the overall activity in agreement with experimental data. Substituent constant values obtained for benzomorphans are used in calculating log (1/C) values for six morphinans. An excellent correlation is obtained (r = 0.95) between the six calculated and observed activities. The possibility of extending the Free-Wilson approach from one series of homologues to another is demonstrated.", "contents": "Application of the Free-Wilson technique to structurally related series of homologues. Quantitative structure-activity relationship studies of narcotic analgetics. A series of benzomorphans with ED50 values determined in vivo by the hot-plate method in mice is analyzed by the modified Free-Wilson method. The QSAR yields 36 substituent constants (ai) with contributions to the overall activity in agreement with experimental data. Substituent constant values obtained for benzomorphans are used in calculating log (1/C) values for six morphinans. An excellent correlation is obtained (r = 0.95) between the six calculated and observed activities. The possibility of extending the Free-Wilson approach from one series of homologues to another is demonstrated."}
{"id": "PMID:21293", "title": "Synthesis of 1-substituted analogues of trimetoquinol possessing differential and selective beta-adrenergic properties.", "content": "The synthesis of the 1,1-disubstituted tetrahydroisoquinoline analogues, 1-methyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (2) and 1-benzyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3), is described. The profile of beta-adrenergic activity for these analogues was determined and compared to that of trimetoquinol (1) in isolated guinea pig atrial, tracheal, and rat adipocyte preparations. Unexpected selective beta1-blocking activity in guinea pig trachea was noted with analogue 3. With the exception of 2 in guinea pig atria, 2 and 3 did not possess any beta-stimulant activity. Substitution at the 1 position of trimetoquinol (1) has revealed qualitative differences in beta-adrenergic activity.", "contents": "Synthesis of 1-substituted analogues of trimetoquinol possessing differential and selective beta-adrenergic properties. The synthesis of the 1,1-disubstituted tetrahydroisoquinoline analogues, 1-methyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (2) and 1-benzyl-1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3), is described. The profile of beta-adrenergic activity for these analogues was determined and compared to that of trimetoquinol (1) in isolated guinea pig atrial, tracheal, and rat adipocyte preparations. Unexpected selective beta1-blocking activity in guinea pig trachea was noted with analogue 3. With the exception of 2 in guinea pig atria, 2 and 3 did not possess any beta-stimulant activity. Substitution at the 1 position of trimetoquinol (1) has revealed qualitative differences in beta-adrenergic activity."}
{"id": "PMID:21294", "title": "A systematic and comprehensive approach to teaching and evaluating interpersonal skills.", "content": "This study addressed one problem with current methods for teaching and evaluating interpersonal skills: the failure to include a wide range of behaviors reported in the literature as contributing to patient dissatisfaction and noncompliance. To address this concern, the authors developed a comprehensive interpersonal skills training program and a pretest-posttest evaluation. The tests were administered to two student groups one of which received the interpersonal skills instruction. The student group exposed to the training exhibited a significant positive change from pretest to posttest. Additionally the change for this group was significantly greater than the change for the group not exposed to interpersonal skills instruction.", "contents": "A systematic and comprehensive approach to teaching and evaluating interpersonal skills. This study addressed one problem with current methods for teaching and evaluating interpersonal skills: the failure to include a wide range of behaviors reported in the literature as contributing to patient dissatisfaction and noncompliance. To address this concern, the authors developed a comprehensive interpersonal skills training program and a pretest-posttest evaluation. The tests were administered to two student groups one of which received the interpersonal skills instruction. The student group exposed to the training exhibited a significant positive change from pretest to posttest. Additionally the change for this group was significantly greater than the change for the group not exposed to interpersonal skills instruction."}
{"id": "PMID:21295", "title": "The effect of certain rater roles on confidence in physician's assistant ratings.", "content": "Previous research on the psychology of confidence suggests that the more confident a rater is in his judgment the more accurate is his rating. The purpose of the present study was to investigate possible differences among raters in their confidence in competency ratings which they had provided. Results indicated significant differences due to the rater's interpersonal role with the ratee and the particular aspect of competence rated. Greater simple structure of competence ratings when adjusted for rater confidence is also shown. Rater confidence is discussed as an index for rater selection and as a moderator variable for competence ratings.", "contents": "The effect of certain rater roles on confidence in physician's assistant ratings. Previous research on the psychology of confidence suggests that the more confident a rater is in his judgment the more accurate is his rating. The purpose of the present study was to investigate possible differences among raters in their confidence in competency ratings which they had provided. Results indicated significant differences due to the rater's interpersonal role with the ratee and the particular aspect of competence rated. Greater simple structure of competence ratings when adjusted for rater confidence is also shown. Rater confidence is discussed as an index for rater selection and as a moderator variable for competence ratings."}
{"id": "PMID:21297", "title": "Normal acid-base status of arterial blood from the conscious, chair-restrained squirrel monkey.", "content": "Normal acid-base status of arterial blood (pHa =7.40, PaCO2=38.1 Torr) was demonstrated for conscious, restrained squirrel monkeys when environmental stimuli were minimized and monkeys are habituated to experimental procedures. These results indicate the potential for using squirrel monkeys in experiments in which normal acid-base status is a significant factor.", "contents": "Normal acid-base status of arterial blood from the conscious, chair-restrained squirrel monkey. Normal acid-base status of arterial blood (pHa =7.40, PaCO2=38.1 Torr) was demonstrated for conscious, restrained squirrel monkeys when environmental stimuli were minimized and monkeys are habituated to experimental procedures. These results indicate the potential for using squirrel monkeys in experiments in which normal acid-base status is a significant factor."}
{"id": "PMID:21298", "title": "Multifocal candidiasis in a capuchin monkey (Cebus apella).", "content": "Candidiasis involving nasal, pharyngeal, and intestinal mucosal surfaces and a pharyngeal lymph node was demonstrated microscopically in a young adult female capuchin monkey (Cebus apella) experimentally infected with Schistosoma haematobium (Iran strain). Persistent nasal exudation and weight loss characterized the clinical disease preceding the animal's death.", "contents": "Multifocal candidiasis in a capuchin monkey (Cebus apella). Candidiasis involving nasal, pharyngeal, and intestinal mucosal surfaces and a pharyngeal lymph node was demonstrated microscopically in a young adult female capuchin monkey (Cebus apella) experimentally infected with Schistosoma haematobium (Iran strain). Persistent nasal exudation and weight loss characterized the clinical disease preceding the animal's death."}
{"id": "PMID:21301", "title": "Management of dental trauma in children and adolescents.", "content": "The emergency treatment of dental trauma has traditionally been handled in the emergency rooms of medical centers, or in the dental office. With increasing emphasis on comprehensive medical care, and the tendency of more recent graduates to locate in rural areas, there is a growing trend for physicians to be involved in providing emergency care for traumatic injuries to the dental and oral tissues. The authors discuss the etiology of dental trauma and the highly psychologic impact of such injuries upon the patient and parents. Techniques for prevention and a comprehensive plan are outlined for systematic history taking and examination. A classification of eight levels of dental injuries (5), techniques for the emergency, and subsequent restorative care are given. Emphasis is placed upon immediate care which can, if necessary, be provided by the physician pending referral to a dentist.", "contents": "Management of dental trauma in children and adolescents. The emergency treatment of dental trauma has traditionally been handled in the emergency rooms of medical centers, or in the dental office. With increasing emphasis on comprehensive medical care, and the tendency of more recent graduates to locate in rural areas, there is a growing trend for physicians to be involved in providing emergency care for traumatic injuries to the dental and oral tissues. The authors discuss the etiology of dental trauma and the highly psychologic impact of such injuries upon the patient and parents. Techniques for prevention and a comprehensive plan are outlined for systematic history taking and examination. A classification of eight levels of dental injuries (5), techniques for the emergency, and subsequent restorative care are given. Emphasis is placed upon immediate care which can, if necessary, be provided by the physician pending referral to a dentist."}
{"id": "PMID:21304", "title": "Nonstructural proteins of herpes simplex virus. I. Purification of the induced DNA polymerase.", "content": "Herpes simplex virus-induced DNA polymerase purified by published methods was found to be contaminated with many others proteins, including virus structural proteins. Thus, DEAE-cellulose and phosphocellulose chromatography were used in combination with affinity chromatography to purify DNA polymerase from herpes simplex virus type 1- and type 2-infected cells. The purified enzyme retained unique features of the herpesvirus-induced DNA polymerase, including a requirement for high salt concentrations for maximal activity, a sensitivity to low phosphonoacetate concentrations, and the capacity to be neutralized by rabbit antiserum to herpesvirus-infected cells. By polyacrylamide gel electrophoresis, the purified DNA polymerase was associated with a virus-induced polypeptide of about 150,000 molecular weight.", "contents": "Nonstructural proteins of herpes simplex virus. I. Purification of the induced DNA polymerase. Herpes simplex virus-induced DNA polymerase purified by published methods was found to be contaminated with many others proteins, including virus structural proteins. Thus, DEAE-cellulose and phosphocellulose chromatography were used in combination with affinity chromatography to purify DNA polymerase from herpes simplex virus type 1- and type 2-infected cells. The purified enzyme retained unique features of the herpesvirus-induced DNA polymerase, including a requirement for high salt concentrations for maximal activity, a sensitivity to low phosphonoacetate concentrations, and the capacity to be neutralized by rabbit antiserum to herpesvirus-infected cells. By polyacrylamide gel electrophoresis, the purified DNA polymerase was associated with a virus-induced polypeptide of about 150,000 molecular weight."}
{"id": "PMID:21305", "title": "Properties of deoxynucleoside 5'-monophosphatase induced by bacteriophage T5 after infection of Escherichia coli.", "content": "Bacteriophage T5 induced a deoxynucleoside 5'-monophosphatase during its infection of Escherichia coli. The enzyme was purified about 100-fold. It was clearly distinct from the host 5'-nucleotidase activity in its physical characteristics and substrate specificity. The enzyme was active on deoxynucleoside 5'-monophosphates but was not active as a phosphatase on ribonucleotides, deoxynucleoside 5'-triphosphates, deoxynucleoside 3'-monophosphates, or deoxyoligonucleotides. Furthermore, it did not have oligonucleotidase or exonuclease activity. The enzyme could exist in multimeric form but had a monomer molecular weight of about 25,000.", "contents": "Properties of deoxynucleoside 5'-monophosphatase induced by bacteriophage T5 after infection of Escherichia coli. Bacteriophage T5 induced a deoxynucleoside 5'-monophosphatase during its infection of Escherichia coli. The enzyme was purified about 100-fold. It was clearly distinct from the host 5'-nucleotidase activity in its physical characteristics and substrate specificity. The enzyme was active on deoxynucleoside 5'-monophosphates but was not active as a phosphatase on ribonucleotides, deoxynucleoside 5'-triphosphates, deoxynucleoside 3'-monophosphates, or deoxyoligonucleotides. Furthermore, it did not have oligonucleotidase or exonuclease activity. The enzyme could exist in multimeric form but had a monomer molecular weight of about 25,000."}
{"id": "PMID:21308", "title": "Renal acidifying ability in subjects with recurrent stone formation.", "content": "To determine the incidence of an acidification defect in men in whom calcium stones form and its relationship to parathyroid function 120 such patients were given an acute dosage of 0.1 gm. per kg. oral ammonium chloride and circulating immunoreactive parathyroid hormone was determined. The subjects were divided into 2 groups, according to normal or high parathormone levels. Group 1 consisted of 46 men in whom immunoreactive parathyroid hormone was less than or equal to 60 mulEq. per ml. and group 2 consisted of 74 men with immunoreactive parathyroid hormone greater than 60 mulEq. per ml. Of 8 men in whom the urine failed to acidify to less than a pH of 5.3, 3 were from group 1 and 5 were from group 2. None of the patients had an active urinary tract infection. There was no difference in minimal urine pH among the patients in whom the urine acidified normally regardless of immunoreactive parathyroid hormone. The incidence of abnormal acidification in our population was 6% and all of these patients had the incomplete form of renal tubular acidosis. These findings have important therapeutic implications.", "contents": "Renal acidifying ability in subjects with recurrent stone formation. To determine the incidence of an acidification defect in men in whom calcium stones form and its relationship to parathyroid function 120 such patients were given an acute dosage of 0.1 gm. per kg. oral ammonium chloride and circulating immunoreactive parathyroid hormone was determined. The subjects were divided into 2 groups, according to normal or high parathormone levels. Group 1 consisted of 46 men in whom immunoreactive parathyroid hormone was less than or equal to 60 mulEq. per ml. and group 2 consisted of 74 men with immunoreactive parathyroid hormone greater than 60 mulEq. per ml. Of 8 men in whom the urine failed to acidify to less than a pH of 5.3, 3 were from group 1 and 5 were from group 2. None of the patients had an active urinary tract infection. There was no difference in minimal urine pH among the patients in whom the urine acidified normally regardless of immunoreactive parathyroid hormone. The incidence of abnormal acidification in our population was 6% and all of these patients had the incomplete form of renal tubular acidosis. These findings have important therapeutic implications."}
{"id": "PMID:21309", "title": "The effect of bicarbonate and distilled water on sickle cell trait hematuria and in vitro studies on the interaction of osmolality and pH on erythrocyte sickling in sickle cell trait.", "content": "The effect of intravenously administered distilled water was examined alone and during alkalization in a patient with gross hematuria associated with the sickle cell trait. On each of 4 occasions hematuria ceased promptly after the infusion of distilled water. Bicarbonate therapy also consistently decreased hematuria. In vitro studies on erythrocytes from another patient with sickle cell trait and hematuria demonstrated that slight increases in urinary pH similar to those that occur in the urine during alkalization can reverse or prevent erythrocyte sickling in the sicle cell trait. If patients with the sickle cell trait are hydrated adequately and have a good rate of urine flow distilled water can be given intravenously with virtually no danger of acute tubular necrosis secondary to erythrocyte hemolysis.", "contents": "The effect of bicarbonate and distilled water on sickle cell trait hematuria and in vitro studies on the interaction of osmolality and pH on erythrocyte sickling in sickle cell trait. The effect of intravenously administered distilled water was examined alone and during alkalization in a patient with gross hematuria associated with the sickle cell trait. On each of 4 occasions hematuria ceased promptly after the infusion of distilled water. Bicarbonate therapy also consistently decreased hematuria. In vitro studies on erythrocytes from another patient with sickle cell trait and hematuria demonstrated that slight increases in urinary pH similar to those that occur in the urine during alkalization can reverse or prevent erythrocyte sickling in the sicle cell trait. If patients with the sickle cell trait are hydrated adequately and have a good rate of urine flow distilled water can be given intravenously with virtually no danger of acute tubular necrosis secondary to erythrocyte hemolysis."}
{"id": "PMID:21310", "title": "Bilateral seminoma 34 years after orchiopexy.", "content": "A case of bilateral seminoma in a 59-year-old patient who had undergone bilateral orchiopexy 34 years previously is presented. To our knowledge this is the longest interval between an orchiopexy and diagnosis of bilateral malignancy.", "contents": "Bilateral seminoma 34 years after orchiopexy. A case of bilateral seminoma in a 59-year-old patient who had undergone bilateral orchiopexy 34 years previously is presented. To our knowledge this is the longest interval between an orchiopexy and diagnosis of bilateral malignancy."}
{"id": "PMID:21311", "title": "Occurrence of rumenitis in a supplementary fed white-tailed deer herd.", "content": "Rumenitis was observed with increased frequency in a herd of white-tailed deer (Odocoileus virginianus) maintained on a high carbohydrate supplemental ration. Healing rumen scars were found in 4.4% (n=225) of animals examined in 1973; 24.1% (n=278) in 1974; and 42.5% (n=308) in 1975. The lesions often involved nearly the entire ventral blind sac of the rumen. Histopathologic studies did not define the etiologic agent and invasion by either fungi or Fusiformis necrophorus was not a prominent feature in the cases examined. Recovery appeared to be complete and the disease was not considered to be an important herd mortality factor.", "contents": "Occurrence of rumenitis in a supplementary fed white-tailed deer herd. Rumenitis was observed with increased frequency in a herd of white-tailed deer (Odocoileus virginianus) maintained on a high carbohydrate supplemental ration. Healing rumen scars were found in 4.4% (n=225) of animals examined in 1973; 24.1% (n=278) in 1974; and 42.5% (n=308) in 1975. The lesions often involved nearly the entire ventral blind sac of the rumen. Histopathologic studies did not define the etiologic agent and invasion by either fungi or Fusiformis necrophorus was not a prominent feature in the cases examined. Recovery appeared to be complete and the disease was not considered to be an important herd mortality factor."}
{"id": "PMID:21318", "title": "Demonstration of vaccinia virus antigen in brains of postvaccinal encephalitis cases.", "content": "Five lethal cases of postovaccinal encephalitis (PVE) were examined in attempts to detect the viral antigen by the fluorescent antibody techniques and to isolate the infectious vaccinia virus. Histologically, the brain tissues were characterized by meningoencephalitis, with perivascular infiltrations and inflammatous reactions mainly in leptomininx, chroid plexus and ependyma. By direct immunofluorescence staining, vaccinia virus antigen was found in the brain specimens of one case, but not in the other four cases. The existence of antigen-antibody complexes was suggested by the deposition of immunoglobulins in the brain specimens. After treatment with 3 M NaSCN solution to dissociate the immunoglobulins from the complex, the viral antigen was demonstrated in specimens of two cases. Localization of viral antigen(s) thus detected coincided with that of meningoencephalitic reactions in the histological examination. Virus isolation on chick embryo chorioallantoic membrane was negative in all cases. Participation of viral pathogenicity in the etiology of PVE is discussed.", "contents": "Demonstration of vaccinia virus antigen in brains of postvaccinal encephalitis cases. Five lethal cases of postovaccinal encephalitis (PVE) were examined in attempts to detect the viral antigen by the fluorescent antibody techniques and to isolate the infectious vaccinia virus. Histologically, the brain tissues were characterized by meningoencephalitis, with perivascular infiltrations and inflammatous reactions mainly in leptomininx, chroid plexus and ependyma. By direct immunofluorescence staining, vaccinia virus antigen was found in the brain specimens of one case, but not in the other four cases. The existence of antigen-antibody complexes was suggested by the deposition of immunoglobulins in the brain specimens. After treatment with 3 M NaSCN solution to dissociate the immunoglobulins from the complex, the viral antigen was demonstrated in specimens of two cases. Localization of viral antigen(s) thus detected coincided with that of meningoencephalitic reactions in the histological examination. Virus isolation on chick embryo chorioallantoic membrane was negative in all cases. Participation of viral pathogenicity in the etiology of PVE is discussed."}
{"id": "PMID:21319", "title": "Prostaglandin synthetase systems in rat and rabbit renal medulla and inhibition by non-steroidal anti-inflammatory drugs.", "content": "The properties of prostaglandin synthetase systems (PSSs) in the renal medulla of the rat and rabbit, and inhibition by ketoprofen, indomethacin, ibuprofen, phenylbutazone and aspirin were investigated in relation to their anti-inflammatory, analgesic, antipyretic and ulcerogenic activities. Rat and rabbit PSSs produced prostaglandin (PG)E and PGF from arachidonic and dihomo-gamma-linolenic acids and had an optimal pH of 8.5 and 7.5 for PGE formation, respectively. Only a slight loss of activity occurred with lyophilization. In the rat PSS, all drugs tested were inhibitory in the order of ketoprofen, ibuprofen, indomethacin and aspirin, respectively. In the rabbit PSS, the same potency relationship was also found. Drug sensitivity of the rat PSS was remarkably lower than that of the rabbit PSS. Significant correlations were noted between the inhibitory potencies of the drugs against both PSSs and other in vivo pharmacological activities within the same species.", "contents": "Prostaglandin synthetase systems in rat and rabbit renal medulla and inhibition by non-steroidal anti-inflammatory drugs. The properties of prostaglandin synthetase systems (PSSs) in the renal medulla of the rat and rabbit, and inhibition by ketoprofen, indomethacin, ibuprofen, phenylbutazone and aspirin were investigated in relation to their anti-inflammatory, analgesic, antipyretic and ulcerogenic activities. Rat and rabbit PSSs produced prostaglandin (PG)E and PGF from arachidonic and dihomo-gamma-linolenic acids and had an optimal pH of 8.5 and 7.5 for PGE formation, respectively. Only a slight loss of activity occurred with lyophilization. In the rat PSS, all drugs tested were inhibitory in the order of ketoprofen, ibuprofen, indomethacin and aspirin, respectively. In the rabbit PSS, the same potency relationship was also found. Drug sensitivity of the rat PSS was remarkably lower than that of the rabbit PSS. Significant correlations were noted between the inhibitory potencies of the drugs against both PSSs and other in vivo pharmacological activities within the same species."}
{"id": "PMID:21321", "title": "[Evaluation of antireflux effect of fundic patch operation by withdrawal pH curve (author's transl)].", "content": "With the use of gastroesophageal withdrawal pH curve, pathophysiology after various surgical procedures for achalasia of the esophagus was investigated experimentally from the view point of postoperative reflux. A total of 68 dogs were divided into four groups and were prepared with proximal gastrectomy with end-to-end esophagogastrostomy, Wendel procedure, Heller procedure and Fundic patch operation, respectively. In the group with Fundic patch operation, efficacy of the flap valve, mucosal valve and fundoplication was also evaluated preparing them in various sizes. The results obtained may be summarized as follows: 1) Withdrawal pH measurement is a sentive mean to detect the gastroesophageal reflux. 2) Proximal gastrectomy with end-to-end esophagogastrostomy and Wendel procedure yielded worst results with severe gastroesophageal reflux. On the contrary, Fundic patch operation best controlled the gastroesophageal reflux. 3) Gastroesophageal reflux could be prevented by the Fundic patch operation with the flap valve 6 cm in length and fundoplication enclosing around 1/2 to 2/3 circumference of the distal esophagus.", "contents": "[Evaluation of antireflux effect of fundic patch operation by withdrawal pH curve (author's transl)]. With the use of gastroesophageal withdrawal pH curve, pathophysiology after various surgical procedures for achalasia of the esophagus was investigated experimentally from the view point of postoperative reflux. A total of 68 dogs were divided into four groups and were prepared with proximal gastrectomy with end-to-end esophagogastrostomy, Wendel procedure, Heller procedure and Fundic patch operation, respectively. In the group with Fundic patch operation, efficacy of the flap valve, mucosal valve and fundoplication was also evaluated preparing them in various sizes. The results obtained may be summarized as follows: 1) Withdrawal pH measurement is a sentive mean to detect the gastroesophageal reflux. 2) Proximal gastrectomy with end-to-end esophagogastrostomy and Wendel procedure yielded worst results with severe gastroesophageal reflux. On the contrary, Fundic patch operation best controlled the gastroesophageal reflux. 3) Gastroesophageal reflux could be prevented by the Fundic patch operation with the flap valve 6 cm in length and fundoplication enclosing around 1/2 to 2/3 circumference of the distal esophagus."}
{"id": "PMID:21323", "title": "[Prostaglandin E1: effect on blood gases in infants with cyanotic congenital heart disease (author's transl)].", "content": "15 infants with cyanotic congenital heart disease (pulmonary atresia, Ebstein-Syndrom) were treated with Prostaglandin E1. During treatment there was a significant rise of PO2 and SO2 in the arterial, capillary and central venous blood. There was a minor rise of pH and HCO3; the arterial pCO2 fell slightly. We used PGE1-therapy as pretreatment before the heart operation, so that the critical babies go to the operation well oxygenated and in a better state. The side effects we observed (tachypnoe, tachycardia, hyperpyrexia, augmented urine output, erythemas, apnoic spells) seemed less important than the great advantage of a better oxygenation of these hypoxic babies.", "contents": "[Prostaglandin E1: effect on blood gases in infants with cyanotic congenital heart disease (author's transl)]. 15 infants with cyanotic congenital heart disease (pulmonary atresia, Ebstein-Syndrom) were treated with Prostaglandin E1. During treatment there was a significant rise of PO2 and SO2 in the arterial, capillary and central venous blood. There was a minor rise of pH and HCO3; the arterial pCO2 fell slightly. We used PGE1-therapy as pretreatment before the heart operation, so that the critical babies go to the operation well oxygenated and in a better state. The side effects we observed (tachypnoe, tachycardia, hyperpyrexia, augmented urine output, erythemas, apnoic spells) seemed less important than the great advantage of a better oxygenation of these hypoxic babies."}
{"id": "PMID:21324", "title": "Detection of circulating immune complexes with a modified Raji cell technique.", "content": "A modification of the Raji cell technique for the detection of circulating immune complexes is described. Raji lymphoid cells bind immune complexes via the C 3 receptor. Prior to incubation with the test serum it is necessary to block the IgG Fc receptor which would interfere with the assay. In the present modification the IgG Fc receptor is blocked with monoclonal IgG myeloma proteins thereby facilitating the detection of C 3 bound immune complexes with fluoresecein-conjugated anti-light chain serum. This modification is presently used in a survey of immune complexes in a number of autoimmune diseases.", "contents": "Detection of circulating immune complexes with a modified Raji cell technique. A modification of the Raji cell technique for the detection of circulating immune complexes is described. Raji lymphoid cells bind immune complexes via the C 3 receptor. Prior to incubation with the test serum it is necessary to block the IgG Fc receptor which would interfere with the assay. In the present modification the IgG Fc receptor is blocked with monoclonal IgG myeloma proteins thereby facilitating the detection of C 3 bound immune complexes with fluoresecein-conjugated anti-light chain serum. This modification is presently used in a survey of immune complexes in a number of autoimmune diseases."}
{"id": "PMID:21325", "title": "Polyanion and complement receptor of the glomerular epithelium. Relationship to pH.", "content": "Two markers on the surface of glomerular epithelial cells were studied on human and rat tissue. The glomerular polyanion is known to be a sialoglycoprotein present profusely on glomerular epithelial cell surfaces, and it is detected by binding with cationic dyes. This staining is lost after incubation in the pH range 3.8 to 4.4, yet retained at a more acidic or physiologic pH. A receptor for complement is also present on human glomerular epithelial cells. This receptor is also lost as a function of varying pH incubation and this loss parallels the pattern observed for glomerular polyanion. Neuraminidase treatment of renal tissue removes the sialic acid-dependent glomerular polyanion staining but preserves and stabilizes the complement receptor. Both functions are markers of the cell surface of glomerular epithelial cells and behave as peripheral membrane proteins.", "contents": "Polyanion and complement receptor of the glomerular epithelium. Relationship to pH. Two markers on the surface of glomerular epithelial cells were studied on human and rat tissue. The glomerular polyanion is known to be a sialoglycoprotein present profusely on glomerular epithelial cell surfaces, and it is detected by binding with cationic dyes. This staining is lost after incubation in the pH range 3.8 to 4.4, yet retained at a more acidic or physiologic pH. A receptor for complement is also present on human glomerular epithelial cells. This receptor is also lost as a function of varying pH incubation and this loss parallels the pattern observed for glomerular polyanion. Neuraminidase treatment of renal tissue removes the sialic acid-dependent glomerular polyanion staining but preserves and stabilizes the complement receptor. Both functions are markers of the cell surface of glomerular epithelial cells and behave as peripheral membrane proteins."}
{"id": "PMID:21329", "title": "On the inactivation of hepatic tyrosine aminotransferase.", "content": "Tyrosine aminotransferase from frog liver requires no exogenous pyridoxal-5'-phosphate for maximum activity. The cofactor cannot be removed from the enzyme by dialysis as in the case of the rat enzyme. Pyridoxal phosphate also fails to elevate frog liver tyrosine aminotransferase activity in vivo. The enzyme activity decreases rapidly after administration of cycloheximide, which indicates that its turnover is rapid. These results strongly contradict the cofactor-dependent model of enzyme degradation. Rat and frog liver tyrosine aminotransferases are stable in neutral homogenates at 37 degrees C but are rapidly inactivated after addition of cysteine in millimolar concentrations. This effect is probably due to cystine formed during the incubation. The rates of inactivation of the different subforms of the enzyme in this system were identical. No membrane-bound system is needed for the inactivation by cystine. It is possible that the denaturation occurs by sulfide exchange. Fructose and glucose lower the enzyme activity in both rat and frog liver to an equal extent. This effect is not due to instability of the enzyme activity in both rat and frog liver to an equal extent. This effect is not due to instability of the enzyme in the presence of sugars of their metabolites. Theories on the inactivation of enzymes will be discussed in the light of the present results.", "contents": "On the inactivation of hepatic tyrosine aminotransferase. Tyrosine aminotransferase from frog liver requires no exogenous pyridoxal-5'-phosphate for maximum activity. The cofactor cannot be removed from the enzyme by dialysis as in the case of the rat enzyme. Pyridoxal phosphate also fails to elevate frog liver tyrosine aminotransferase activity in vivo. The enzyme activity decreases rapidly after administration of cycloheximide, which indicates that its turnover is rapid. These results strongly contradict the cofactor-dependent model of enzyme degradation. Rat and frog liver tyrosine aminotransferases are stable in neutral homogenates at 37 degrees C but are rapidly inactivated after addition of cysteine in millimolar concentrations. This effect is probably due to cystine formed during the incubation. The rates of inactivation of the different subforms of the enzyme in this system were identical. No membrane-bound system is needed for the inactivation by cystine. It is possible that the denaturation occurs by sulfide exchange. Fructose and glucose lower the enzyme activity in both rat and frog liver to an equal extent. This effect is not due to instability of the enzyme activity in both rat and frog liver to an equal extent. This effect is not due to instability of the enzyme in the presence of sugars of their metabolites. Theories on the inactivation of enzymes will be discussed in the light of the present results."}
{"id": "PMID:21328", "title": "Model membranes for the study of active transport phenomena.", "content": "Models for active transport are prepared by the covalent bonding of molecules containing a catalytic site to the membrane asymmetrically with respect to its thickness. The membrane separates two compartments of unequal volume, both initially containing reactant at the same concentration. We observed the time dependence of the reactant and product concentrations, and of the osmotic pressure, and these results are compared with theoretical predictions. The two reactions studied are the hydrolysis of ethyl N-acetyl-L-tyrosinate catalyzed by alpha-chymotrypsin and the acid-catalyzed hydrolysis of triethoxymethane. The asymmetric membrane consumes reactant, and discharges product, at different rates through its two faces. The concentration of products, and of non-rate determining reactants, may exhibit maxima or minima with time, and computer simulation indicates that oscillatory behavior could be expected under appropriate conditions. Due to the different exit path lengths, the osmotic response (determined by the solute concentrations at the two membrane surfaces) may be opposite in sign to that expected from the concentrations in the external compartments.", "contents": "Model membranes for the study of active transport phenomena. Models for active transport are prepared by the covalent bonding of molecules containing a catalytic site to the membrane asymmetrically with respect to its thickness. The membrane separates two compartments of unequal volume, both initially containing reactant at the same concentration. We observed the time dependence of the reactant and product concentrations, and of the osmotic pressure, and these results are compared with theoretical predictions. The two reactions studied are the hydrolysis of ethyl N-acetyl-L-tyrosinate catalyzed by alpha-chymotrypsin and the acid-catalyzed hydrolysis of triethoxymethane. The asymmetric membrane consumes reactant, and discharges product, at different rates through its two faces. The concentration of products, and of non-rate determining reactants, may exhibit maxima or minima with time, and computer simulation indicates that oscillatory behavior could be expected under appropriate conditions. Due to the different exit path lengths, the osmotic response (determined by the solute concentrations at the two membrane surfaces) may be opposite in sign to that expected from the concentrations in the external compartments."}
{"id": "PMID:21340", "title": "Use of prazosin at the dunedin hypertension clinic controlled and open studies and pharmacokinetic observations.", "content": "Prazosin has been used as an antihypertensive drug in the treatment of 93 patients in Dunedin since 1971-1972, mainly those whose previous control was unsatisfactory. It has led to very significant improvement of control in many cases; 48 patients now receiving the drug have taken it for an average of 30 months. Forty-five patients have stopped taking the drug for various reasons, such as failure to respond (11-8%), side effects (20-4%), myocardial infarction (8-6%) or unrelated reasons (7-5%). This reflects to some extent the use ofa new drug in patients who are difficult to control, and its use initially without concomitant diuretic and beta-blocker therapy. We believe that the place of praxosin is primarily as a third drug for patients whose hypertension does not respond satisfactorirly to a diuretic and a beta-blocker. The first dose must be kept small, preferably 0-25 mg, and even with this dose a small proportion of patients receiving diuretic and beta-blocker therapy seem to become hypotensive; patients should be warned about this. The plasma half-life in normal volunteers was 3-8 hours but in some patients it seems to be considerably longer.", "contents": "Use of prazosin at the dunedin hypertension clinic controlled and open studies and pharmacokinetic observations. Prazosin has been used as an antihypertensive drug in the treatment of 93 patients in Dunedin since 1971-1972, mainly those whose previous control was unsatisfactory. It has led to very significant improvement of control in many cases; 48 patients now receiving the drug have taken it for an average of 30 months. Forty-five patients have stopped taking the drug for various reasons, such as failure to respond (11-8%), side effects (20-4%), myocardial infarction (8-6%) or unrelated reasons (7-5%). This reflects to some extent the use ofa new drug in patients who are difficult to control, and its use initially without concomitant diuretic and beta-blocker therapy. We believe that the place of praxosin is primarily as a third drug for patients whose hypertension does not respond satisfactorirly to a diuretic and a beta-blocker. The first dose must be kept small, preferably 0-25 mg, and even with this dose a small proportion of patients receiving diuretic and beta-blocker therapy seem to become hypotensive; patients should be warned about this. The plasma half-life in normal volunteers was 3-8 hours but in some patients it seems to be considerably longer."}
{"id": "PMID:21345", "title": "[On the action of antihypotensive agents in sympathicotonic orthostatic hypotension in geriartric patients: comparison between placebo and etilefrin (author's transl)].", "content": "The action of etilefrin (Effortil Depot Perlongets) was compared with placebo in a double-blind study in 24 female geriatric patients with sympathicotonic orthostatic hypotension. After determining the basic values, all patients were treated with the active substance in a titration phase lasting one week (dosage 2-3 Perlongets/day). The decrease in systolic blood pressure and the increase in pulse rate while standing were then statistically significant lower (p less than (p less than 0.001) when compared with the basic values. In 17 out of 21 cases of collapse which occured while standing before therapy was commenced no further collapse occurred (p less than 0.005). Following the titration phase treatment with etilefrin was continued in 12 patients in a double-blind study while the remaining 12 patients were changed over to placebo as a withdrawal study. The effect continued in those patients treated with the active ingredient and the average values and incidence of effects improved further. On the other hand, in the placebo group there was one again a marked decrease in systolic blood pressure and increase in pulse rate as observed in the basic values. The symptomatology, particulary episodes of collapse increased again. There was a statistically significant difference between the action of etilefrin and placebo for all criteria (both objective and subjective parameters). Side-effects were not observed.", "contents": "[On the action of antihypotensive agents in sympathicotonic orthostatic hypotension in geriartric patients: comparison between placebo and etilefrin (author's transl)]. The action of etilefrin (Effortil Depot Perlongets) was compared with placebo in a double-blind study in 24 female geriatric patients with sympathicotonic orthostatic hypotension. After determining the basic values, all patients were treated with the active substance in a titration phase lasting one week (dosage 2-3 Perlongets/day). The decrease in systolic blood pressure and the increase in pulse rate while standing were then statistically significant lower (p less than (p less than 0.001) when compared with the basic values. In 17 out of 21 cases of collapse which occured while standing before therapy was commenced no further collapse occurred (p less than 0.005). Following the titration phase treatment with etilefrin was continued in 12 patients in a double-blind study while the remaining 12 patients were changed over to placebo as a withdrawal study. The effect continued in those patients treated with the active ingredient and the average values and incidence of effects improved further. On the other hand, in the placebo group there was one again a marked decrease in systolic blood pressure and increase in pulse rate as observed in the basic values. The symptomatology, particulary episodes of collapse increased again. There was a statistically significant difference between the action of etilefrin and placebo for all criteria (both objective and subjective parameters). Side-effects were not observed."}
{"id": "PMID:21348", "title": "Mutagenesis by simian virus 40. II. Changes in substrate affinities in mutant hypoxanthine-guanine phosphoribosyl transferase enzymes at different pH values.", "content": "A number of 8-azaguanine-resistant clones selected from Chinese hamster cells infected with SV 40, and supposed to originate by virus infection was investigated to demonstrate and analyze genetic alterations occurring in the cells after infection. All resistant clones tested showed reduced but detectable activity levels of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The extent of reduction in the activity was not identical for different substrates. In all the clones tested, spontaneous mutants included, the pH optimum for the enzymic reaction with guanine was shifted to lower values. The reduced enzymic activities of resistant clones correlated with their colony-forming ability in corresponding selective media. The results support the suggestion that SV 40 is able to induce gene mutations.", "contents": "Mutagenesis by simian virus 40. II. Changes in substrate affinities in mutant hypoxanthine-guanine phosphoribosyl transferase enzymes at different pH values. A number of 8-azaguanine-resistant clones selected from Chinese hamster cells infected with SV 40, and supposed to originate by virus infection was investigated to demonstrate and analyze genetic alterations occurring in the cells after infection. All resistant clones tested showed reduced but detectable activity levels of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The extent of reduction in the activity was not identical for different substrates. In all the clones tested, spontaneous mutants included, the pH optimum for the enzymic reaction with guanine was shifted to lower values. The reduced enzymic activities of resistant clones correlated with their colony-forming ability in corresponding selective media. The results support the suggestion that SV 40 is able to induce gene mutations."}
{"id": "PMID:21349", "title": "Bacterial stimulation and granulocyte inhibition of granulopoietic factor production.", "content": "We attempted to determine the effect of live bacteria (Staphylococcus epidermidis) on granulocyte colony-stimulating-factor production by human peripheral blood mononuclear cells (monocytes and lymphocytes) in vitro. Addition of bacteria to mononuclear-cell cultures enhanced colony-stimulating-factor production by these cells, as assayed on both human and mouse bone marrow. Addition of peripheral blood granulocytes to parallel cultures eliminated this enhancement effect, presumably by bacterial removal or inactivation. These data suggest that micro-organisms may have a pivotal role in granulocyte production and maturation by serving as a stimulus to increase colony-stimulating-factor production and also as negative control through their removal by the newly formed granulocytes.", "contents": "Bacterial stimulation and granulocyte inhibition of granulopoietic factor production. We attempted to determine the effect of live bacteria (Staphylococcus epidermidis) on granulocyte colony-stimulating-factor production by human peripheral blood mononuclear cells (monocytes and lymphocytes) in vitro. Addition of bacteria to mononuclear-cell cultures enhanced colony-stimulating-factor production by these cells, as assayed on both human and mouse bone marrow. Addition of peripheral blood granulocytes to parallel cultures eliminated this enhancement effect, presumably by bacterial removal or inactivation. These data suggest that micro-organisms may have a pivotal role in granulocyte production and maturation by serving as a stimulus to increase colony-stimulating-factor production and also as negative control through their removal by the newly formed granulocytes."}
{"id": "PMID:21351", "title": "Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor.", "content": "A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.", "contents": "Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor."}
{"id": "PMID:21354", "title": "[Information transmission by means of neurosecretory peptides as mediators].", "content": "Morphological indications and new experimental results demonstrate that neurosecretory peptides or low-molecular proteins, respectively, appear to effect as mediators in information transmission. They are acting as releasers triggering specific behavior programs in the nervous system or as modulators in the regulation of different functions. This can be observed in different groups of the animal kingdom including mammals and man as well as different levels of organization or systems. Some of such facts at behavior level, concerning regulation of organ function and finally at cellular level of distinct single neurons are discussed.", "contents": "[Information transmission by means of neurosecretory peptides as mediators]. Morphological indications and new experimental results demonstrate that neurosecretory peptides or low-molecular proteins, respectively, appear to effect as mediators in information transmission. They are acting as releasers triggering specific behavior programs in the nervous system or as modulators in the regulation of different functions. This can be observed in different groups of the animal kingdom including mammals and man as well as different levels of organization or systems. Some of such facts at behavior level, concerning regulation of organ function and finally at cellular level of distinct single neurons are discussed."}
{"id": "PMID:21371", "title": "[Possibilities of treatment of maldescensus testis in the dog (author's transl)].", "content": "The diagnosis of inguinal retention of the testis can be made in the dog from the 10th week of life. Like in man, therapy of this condition can be done with gonadotropins or releasing hormones. In conditions with retention of the testicles in the upper inguinal region LH-RH proved to be more successful than gonadotropin. 10 out of 16 patients showed a complete descent of the testes. In addition the effect of plasmagonadotropin as well as urinary chorionic gonadotropin, and of LH-RH on the plasma testosterone levels of juvenile and adult dogs was studied. It could be seen that in the young dogs all 3 hormones caused an increase in plasma testosterone, while in the adult animal only LH-RH was able to produce a significant rise.", "contents": "[Possibilities of treatment of maldescensus testis in the dog (author's transl)]. The diagnosis of inguinal retention of the testis can be made in the dog from the 10th week of life. Like in man, therapy of this condition can be done with gonadotropins or releasing hormones. In conditions with retention of the testicles in the upper inguinal region LH-RH proved to be more successful than gonadotropin. 10 out of 16 patients showed a complete descent of the testes. In addition the effect of plasmagonadotropin as well as urinary chorionic gonadotropin, and of LH-RH on the plasma testosterone levels of juvenile and adult dogs was studied. It could be seen that in the young dogs all 3 hormones caused an increase in plasma testosterone, while in the adult animal only LH-RH was able to produce a significant rise."}
{"id": "PMID:21372", "title": "Comparative study of beta andreoceptor antagonists on the isolated  atria of control and of the reserpine treated rabbits.", "content": "The effect of four adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic response to isoprenaline on isolated rabbit atria. Oxprenolol was the most potent antagonist of the isoprenaline induced cardiac arrhythmias. Alprenolol, practolol and propranolol also blocked the positive chronotropic responses to isoprenaline effectively. All the antagonists lowered the resting heart rate. The effects of all four selected antagonists on heart rate probably result from cardiac beta adrenoceptor blockade. Atria isolated from reserpine treated rabbits, showed a reduced percentage of increase in the heart rate in response to addition of isoprenaline. This decreased response has been related in some cases to direct myocardial inhibition.", "contents": "Comparative study of beta andreoceptor antagonists on the isolated  atria of control and of the reserpine treated rabbits. The effect of four adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic response to isoprenaline on isolated rabbit atria. Oxprenolol was the most potent antagonist of the isoprenaline induced cardiac arrhythmias. Alprenolol, practolol and propranolol also blocked the positive chronotropic responses to isoprenaline effectively. All the antagonists lowered the resting heart rate. The effects of all four selected antagonists on heart rate probably result from cardiac beta adrenoceptor blockade. Atria isolated from reserpine treated rabbits, showed a reduced percentage of increase in the heart rate in response to addition of isoprenaline. This decreased response has been related in some cases to direct myocardial inhibition."}
{"id": "PMID:21378", "title": "Arginine esterase and lysosomal hydrolases in liver from cystic fibrosis subjects.", "content": "The total activity and isoelectric focusing patterns of arginine esterase, cathepsin B1, and several lysosomal hydrolases were normal in liver from two patients with cystic fibrosis. No abnormalities were observed in values for pH optimum, Km, and Vmax for arginine esterase and cathepsin B1 in liver from cystic fibrosis patients compared to those values for liver from the control subject. Soybean trypsin inhibitor at concentrations up to 100 microgram/ml had no effect on liver arginine esterase or cathepsin B1.", "contents": "Arginine esterase and lysosomal hydrolases in liver from cystic fibrosis subjects. The total activity and isoelectric focusing patterns of arginine esterase, cathepsin B1, and several lysosomal hydrolases were normal in liver from two patients with cystic fibrosis. No abnormalities were observed in values for pH optimum, Km, and Vmax for arginine esterase and cathepsin B1 in liver from cystic fibrosis patients compared to those values for liver from the control subject. Soybean trypsin inhibitor at concentrations up to 100 microgram/ml had no effect on liver arginine esterase or cathepsin B1."}
{"id": "PMID:21381", "title": "Problems in assessment of vividness and control of imagery.", "content": "Difficulties in assessing individual differences in vividness and control of mental imagery hinder understanding of the role of of imagery in various phenomena. This study examined the relationships among the Gordon test of imagery control, the Betts questionnaire on imagery vividness, and a research questionnaire on control of imagery developed for this study. The research questionnaire demonstrated satisfactory internal consistency and scores were more widely distributed than were those on the Gordon test. Correlations among the instruments ranged from .47 to .57, suggesting that vividness and control of imagery are not clearly differentiated in practice. Discussion of these results suggests that further empirical work is needed to establish the differential validity of the two constructs.", "contents": "Problems in assessment of vividness and control of imagery. Difficulties in assessing individual differences in vividness and control of mental imagery hinder understanding of the role of of imagery in various phenomena. This study examined the relationships among the Gordon test of imagery control, the Betts questionnaire on imagery vividness, and a research questionnaire on control of imagery developed for this study. The research questionnaire demonstrated satisfactory internal consistency and scores were more widely distributed than were those on the Gordon test. Correlations among the instruments ranged from .47 to .57, suggesting that vividness and control of imagery are not clearly differentiated in practice. Discussion of these results suggests that further empirical work is needed to establish the differential validity of the two constructs."}
{"id": "PMID:21382", "title": "Heat stable inhibitors produced in raw milk.", "content": "Twenty raw farm milk samples were tested for inhibitory substances before and after being kept at room temperature until the pH fell to less than 6.3 but greater than 6.2. The tests were done using the IDF-method and the commercial Thermocult method. In both methods B. stearothermophilus var. chalidolactis is used as the test organism. In two instances a thermostable inhibitor was produced with an inhibitory potential greater than 0.01 IU/ml penicillin standard. The IDF-method was found unsuitable for the study of relatively small concentrations of antibiotics or other chemotherapeutics in milk.", "contents": "Heat stable inhibitors produced in raw milk. Twenty raw farm milk samples were tested for inhibitory substances before and after being kept at room temperature until the pH fell to less than 6.3 but greater than 6.2. The tests were done using the IDF-method and the commercial Thermocult method. In both methods B. stearothermophilus var. chalidolactis is used as the test organism. In two instances a thermostable inhibitor was produced with an inhibitory potential greater than 0.01 IU/ml penicillin standard. The IDF-method was found unsuitable for the study of relatively small concentrations of antibiotics or other chemotherapeutics in milk."}
{"id": "PMID:21383", "title": "[Septicemia in the elderly (author's transl)].", "content": "Out of 1,251 patients above 65 years of age staying at the Charles Foix Hospital (prolonged hospitalization) and the St. Joseph Hospital (acute cases), 168 had one or more positive blood cultures. Urinary tract infection is a major source of septicemia due to gram negative bacilli. It is important to stress cases of septicemia due to pneumococcal pneumoniae, eschars, and other skin lesions. Mortality varies between 33 and 36%, depending upon the hospital. Collapse, although infrequent, still portends a grave prognosis (61% of cases of collapse led to death at Charles Foix Hospital). The combination of more than two risk factors considerably worsens the prognosis. Hypoproteinemia and dementia are every bit as grave as diabetes and cancer. A better isolation of the microorganisms involved in cases of septicemia in the elderly will lead to a more judicious choice of antibiotics. The administration of chemotherapy immediately after the samples were obtained remains the main guarantee of successful therapy.", "contents": "[Septicemia in the elderly (author's transl)]. Out of 1,251 patients above 65 years of age staying at the Charles Foix Hospital (prolonged hospitalization) and the St. Joseph Hospital (acute cases), 168 had one or more positive blood cultures. Urinary tract infection is a major source of septicemia due to gram negative bacilli. It is important to stress cases of septicemia due to pneumococcal pneumoniae, eschars, and other skin lesions. Mortality varies between 33 and 36%, depending upon the hospital. Collapse, although infrequent, still portends a grave prognosis (61% of cases of collapse led to death at Charles Foix Hospital). The combination of more than two risk factors considerably worsens the prognosis. Hypoproteinemia and dementia are every bit as grave as diabetes and cancer. A better isolation of the microorganisms involved in cases of septicemia in the elderly will lead to a more judicious choice of antibiotics. The administration of chemotherapy immediately after the samples were obtained remains the main guarantee of successful therapy."}
{"id": "PMID:21384", "title": "[Hereditary deficiency in the enzymes of the biosynthesis of collagen. The Ehlers-Danlos syndromes (author's transl)].", "content": "The mechanism of the biosynthetic pathway of collagen is briefly summarised. The hereditary enzyme deficiencies of this pathway concern some of the Ehlers-Danlos syndromes. Seven clinically well defined varieties of these syndromes have been recognized, all presenting, as common feature, an hyperextensivitry of joints and hyperelastic, excessively fragile skin. In three of these seven varieties, the enzyme defect has been recently discovered: the type V (associated with chromosome X) is characterized by the deficiency in the lysyl-oxidase, the type VI (ocular) by the deficiency in lysyl-hydroylase; in the type VII (arthrolaxis multiplex congenita) the activity of tropocollagen-peptidase is practically absent. These enzyme deficiencies provide a molecular basis for the interpretation of the pathogenesis of these varieties of the Ehlers-Danlos syndrome.", "contents": "[Hereditary deficiency in the enzymes of the biosynthesis of collagen. The Ehlers-Danlos syndromes (author's transl)]. The mechanism of the biosynthetic pathway of collagen is briefly summarised. The hereditary enzyme deficiencies of this pathway concern some of the Ehlers-Danlos syndromes. Seven clinically well defined varieties of these syndromes have been recognized, all presenting, as common feature, an hyperextensivitry of joints and hyperelastic, excessively fragile skin. In three of these seven varieties, the enzyme defect has been recently discovered: the type V (associated with chromosome X) is characterized by the deficiency in the lysyl-oxidase, the type VI (ocular) by the deficiency in lysyl-hydroylase; in the type VII (arthrolaxis multiplex congenita) the activity of tropocollagen-peptidase is practically absent. These enzyme deficiencies provide a molecular basis for the interpretation of the pathogenesis of these varieties of the Ehlers-Danlos syndrome."}
{"id": "PMID:21388", "title": "Outpatient management of pediatric surgical problems.", "content": "A number of pediatric surgical problems commonly seen in the outpatient department or physician's office are reviewed. It is particularly important for the primary care physician to recognize the difficulty of accurate diagnosis in children and the advantage of sedation in improving patient cooperation. Hospitalization may be necessary for adequate observation, proper preparation for diagnostic studies, or safe treatment. Simple traumatic injuries or infections can usually be treated effectively without hospitalization if sound surgical principles are observed. Abdominal pain or rectal bleeding calls for a careful investigation for early signs of inflammatory disease or life-threatening lesions requiring surgical treatment.", "contents": "Outpatient management of pediatric surgical problems. A number of pediatric surgical problems commonly seen in the outpatient department or physician's office are reviewed. It is particularly important for the primary care physician to recognize the difficulty of accurate diagnosis in children and the advantage of sedation in improving patient cooperation. Hospitalization may be necessary for adequate observation, proper preparation for diagnostic studies, or safe treatment. Simple traumatic injuries or infections can usually be treated effectively without hospitalization if sound surgical principles are observed. Abdominal pain or rectal bleeding calls for a careful investigation for early signs of inflammatory disease or life-threatening lesions requiring surgical treatment."}
{"id": "PMID:21390", "title": "[Influence of pH on nisin production by Streptococcus lactis cultures].", "content": "The pH effect on the nisine biosynthesis during the cultivation of Streptococcus lactis was studied at pH 5,8 6,7 and 7,2. The pH maintenance at the specified level did not stimulate the growth of Str. lactis, did not increase the total yield of nisine and did not produce a significant effect on the level or cellular nisine. This indicates an important physiological difference between the culture-nisine producer described by Hirsh and our culture Str. lactis, str. Moscow University.", "contents": "[Influence of pH on nisin production by Streptococcus lactis cultures]. The pH effect on the nisine biosynthesis during the cultivation of Streptococcus lactis was studied at pH 5,8 6,7 and 7,2. The pH maintenance at the specified level did not stimulate the growth of Str. lactis, did not increase the total yield of nisine and did not produce a significant effect on the level or cellular nisine. This indicates an important physiological difference between the culture-nisine producer described by Hirsh and our culture Str. lactis, str. Moscow University."}
{"id": "PMID:21420", "title": "Effects of neuroleptics on morphine-induced tail erection in mice.", "content": "Morphine elicits dose-dependent tail erection in mice. Pretreatment of mice with atropine, phenoxybenzamine, propranolol, diphenhydramine, cyproheptadine or parachlorophenylalanine did not interfere with tail erection induced by morphone. Several neuroleptic drugs which are dopamine receptor blocking agents showed a clear antagonistic effect on morphine-induced tail erection (MITE). Haloperidol and penfluridol blocked MITE at doses which only produced a slight behavioral depression. Pimozide and chlorpromazine were less antagonistic than haloperidol and penfluridol and inhibited MITE only at doses which produced a marked behavioral depression. Results indicated that dopamine might be involved in tail erection induced by morphine. MITE in mice might be a useful model for the evaluation of neuroleptic drugs.", "contents": "Effects of neuroleptics on morphine-induced tail erection in mice. Morphine elicits dose-dependent tail erection in mice. Pretreatment of mice with atropine, phenoxybenzamine, propranolol, diphenhydramine, cyproheptadine or parachlorophenylalanine did not interfere with tail erection induced by morphone. Several neuroleptic drugs which are dopamine receptor blocking agents showed a clear antagonistic effect on morphine-induced tail erection (MITE). Haloperidol and penfluridol blocked MITE at doses which only produced a slight behavioral depression. Pimozide and chlorpromazine were less antagonistic than haloperidol and penfluridol and inhibited MITE only at doses which produced a marked behavioral depression. Results indicated that dopamine might be involved in tail erection induced by morphine. MITE in mice might be a useful model for the evaluation of neuroleptic drugs."}
{"id": "PMID:21421", "title": "Combination operant conditioning--liquid nitrogen immersion chamber for studying neurotransmitter systems and behavior.", "content": "Studies of neurochemical events associated with behavior require a method of tissue fixation that is rapid and does not itself produce neurochemical changes. An apparatus is described that permits immediate immersion of an unrestrained behaving animal into liquid nitrogen. This method of tissue fixation has the greatest versatility for studying multiple neurotransmitter systems. In addition to the measurement of neurotransmitter content and turnover, investigation of neurotransmitter receptors, enriched nerve ending fractions and enzyme activities are possible. The operant conditioning-liquid nitrogen immersion chamber described here can be used for studying these neurotransmitter systems as they relate to animal's responding on operant schedules of reinforcement.", "contents": "Combination operant conditioning--liquid nitrogen immersion chamber for studying neurotransmitter systems and behavior. Studies of neurochemical events associated with behavior require a method of tissue fixation that is rapid and does not itself produce neurochemical changes. An apparatus is described that permits immediate immersion of an unrestrained behaving animal into liquid nitrogen. This method of tissue fixation has the greatest versatility for studying multiple neurotransmitter systems. In addition to the measurement of neurotransmitter content and turnover, investigation of neurotransmitter receptors, enriched nerve ending fractions and enzyme activities are possible. The operant conditioning-liquid nitrogen immersion chamber described here can be used for studying these neurotransmitter systems as they relate to animal's responding on operant schedules of reinforcement."}
{"id": "PMID:21422", "title": "Potentiation of beta-sympathomimetics with alpha-adrenoceptor blocking drugs in guinea pig trachea and human bronchus preparations.", "content": "The actions of beta-sympathomimetics alone and in various combinations with alpha-adrenoceptor blocking agents were studied in guinea pig tracheal chain and in some preparations of human bronchi taken in operations. All the alpha-adrenoceptor blockers caused 50-100% potentiation of the effects of the beta-sympathomimetics studied in both preparations, had no effects of their own in the rather low concentrations used (10(-10) --10(-6) mol/l). The results show that guinea pig and human tracheobronchial smooth muscle react similarly to these drugs and may contain adrenergic alpha-receptors.", "contents": "Potentiation of beta-sympathomimetics with alpha-adrenoceptor blocking drugs in guinea pig trachea and human bronchus preparations. The actions of beta-sympathomimetics alone and in various combinations with alpha-adrenoceptor blocking agents were studied in guinea pig tracheal chain and in some preparations of human bronchi taken in operations. All the alpha-adrenoceptor blockers caused 50-100% potentiation of the effects of the beta-sympathomimetics studied in both preparations, had no effects of their own in the rather low concentrations used (10(-10) --10(-6) mol/l). The results show that guinea pig and human tracheobronchial smooth muscle react similarly to these drugs and may contain adrenergic alpha-receptors."}
{"id": "PMID:21429", "title": "Norepinephrine-sensitive adenylate cyclase in rat hypothalamus: effects of adrenergic blockers and narcotics.", "content": "The norepinephrine-sensitive adenylate cyclase system in the rat brain was examined. Adrenergic blocking agents and the relative activity of structurally related catecholamines were employed to determine whether norepinephrine-stimulated accumulation of [3H]c-AMP in the hypothalamus occurred via alpha or beta adrenergic receptors. The results indicate that norepinephrine probably acts through a mixture of alpha and beta receptors in that both alpha and beta adrenergic blockers inhibited norepinephrine-induced accumulation of [3H]c-AMP. Morphine and levorphanol had no significant effect on adenylate cyclase or phosphodiesterase activities in hypothalamic slices or homogenates of several brain regions.", "contents": "Norepinephrine-sensitive adenylate cyclase in rat hypothalamus: effects of adrenergic blockers and narcotics. The norepinephrine-sensitive adenylate cyclase system in the rat brain was examined. Adrenergic blocking agents and the relative activity of structurally related catecholamines were employed to determine whether norepinephrine-stimulated accumulation of [3H]c-AMP in the hypothalamus occurred via alpha or beta adrenergic receptors. The results indicate that norepinephrine probably acts through a mixture of alpha and beta receptors in that both alpha and beta adrenergic blockers inhibited norepinephrine-induced accumulation of [3H]c-AMP. Morphine and levorphanol had no significant effect on adenylate cyclase or phosphodiesterase activities in hypothalamic slices or homogenates of several brain regions."}
{"id": "PMID:21430", "title": "Determination of 3-methoxy-4-hydroxyphenylglycol in urine and the effect of diet on its excretion.", "content": "A modified method is described for determination of 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine by gas chromatography with electron capture detection. The method is reproducible and mean (+/- SD) recoveries of MHPG from urine were 78.5 +/- 12.7% and 76.5 +/- 15.0% in two separate series of analyses. Mean 24-hour MHPG excretion was 1884 +/- 591 microgram in 11 normal subjects and 1688 +/- 593 microgram in 20 patients with various types of depression. Males excreted more MHPG than females but this difference could be eliminated by expressing the values relative to the creatinine in urine. Variations in diet did not appear to influence urinary MHPG excretion.", "contents": "Determination of 3-methoxy-4-hydroxyphenylglycol in urine and the effect of diet on its excretion. A modified method is described for determination of 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine by gas chromatography with electron capture detection. The method is reproducible and mean (+/- SD) recoveries of MHPG from urine were 78.5 +/- 12.7% and 76.5 +/- 15.0% in two separate series of analyses. Mean 24-hour MHPG excretion was 1884 +/- 591 microgram in 11 normal subjects and 1688 +/- 593 microgram in 20 patients with various types of depression. Males excreted more MHPG than females but this difference could be eliminated by expressing the values relative to the creatinine in urine. Variations in diet did not appear to influence urinary MHPG excretion."}
{"id": "PMID:21433", "title": "Properties of blood oxygen transport in the turtle Pseudemys scripta and the tortoise Testudo graeca: effects of temperature, CO2 and pH.", "content": "Properties of oxygen-haemoglobin binding have been investigated in the aquatic turtle Psuedemys scripta and the terrestrial tortoise Testudo graeca. Haematocrit (30-35%) and haemoglobin concentration (12-14 g/100 ml blood) were similar in both species. P50 at physiological levels of PCO2 (20-25 mm Hg) was 21 mm Hg in Pseudemys, compared with 23 mm Hg in Testudo. The Bohr shift of the blood of both the turtle and the tortoise was almost identical at -0.28. The heat of oxygenation, deltaH, reflecting the temperature sensitivity of O2-Hb affinity, was -10.55 in Pseudemys and -8.12 kcal/mol in Testudo. These data on whole blood do not support previous generalizations in the literature suggesting marked differences in oxygen-haemoglobin binding between aquatic and terrestrial chelonian reptiles.", "contents": "Properties of blood oxygen transport in the turtle Pseudemys scripta and the tortoise Testudo graeca: effects of temperature, CO2 and pH. Properties of oxygen-haemoglobin binding have been investigated in the aquatic turtle Psuedemys scripta and the terrestrial tortoise Testudo graeca. Haematocrit (30-35%) and haemoglobin concentration (12-14 g/100 ml blood) were similar in both species. P50 at physiological levels of PCO2 (20-25 mm Hg) was 21 mm Hg in Pseudemys, compared with 23 mm Hg in Testudo. The Bohr shift of the blood of both the turtle and the tortoise was almost identical at -0.28. The heat of oxygenation, deltaH, reflecting the temperature sensitivity of O2-Hb affinity, was -10.55 in Pseudemys and -8.12 kcal/mol in Testudo. These data on whole blood do not support previous generalizations in the literature suggesting marked differences in oxygen-haemoglobin binding between aquatic and terrestrial chelonian reptiles."}
{"id": "PMID:21434", "title": "Oxygen affinity of avian blood.", "content": "Oxygen dissociation curves plotted directly on whole blood during oxygenation using a Radiometer DCA 1 gave P50 values of 39.2 +/- 2.2 mm Hg and 51.3 +/- 6.2 mm Hg for pigeon and chicken blood, respectively, at 41 degrees C, pH 7.5 and PCO2 29 mm Hg. These values agree well with earlier results obtained by a variety of methods; however, they do conflict with recent findings of a much higher oxygen affinity in avian blood which were obtained using a different plotting method. It was shown that with the method used in this paper the high metabolic rate of avian blood has little effect on the plotted curve at saturations below 50%. At higher saturations O2 consumption of red cells affects a progressive shift of the curve to the left so that to obtain accurate curves at high saturation it is necessary to correct the plotted curves for the oxygen utilization.", "contents": "Oxygen affinity of avian blood. Oxygen dissociation curves plotted directly on whole blood during oxygenation using a Radiometer DCA 1 gave P50 values of 39.2 +/- 2.2 mm Hg and 51.3 +/- 6.2 mm Hg for pigeon and chicken blood, respectively, at 41 degrees C, pH 7.5 and PCO2 29 mm Hg. These values agree well with earlier results obtained by a variety of methods; however, they do conflict with recent findings of a much higher oxygen affinity in avian blood which were obtained using a different plotting method. It was shown that with the method used in this paper the high metabolic rate of avian blood has little effect on the plotted curve at saturations below 50%. At higher saturations O2 consumption of red cells affects a progressive shift of the curve to the left so that to obtain accurate curves at high saturation it is necessary to correct the plotted curves for the oxygen utilization."}
{"id": "PMID:21435", "title": "Gas exchange and acid-base regulation in the blood and extraembryonic fluids of the developing chicken embryo.", "content": "Measurements of pH, PCO2, PO2 and total CO2 were recorded simultaneously in samples of chorioallantoic fluid, amnionic fluid and blood of the chorioallantoic artery from chicken embryos on days 8, 10, 12, 14, 16, 17 and 18 of incubation. During the incubation period studied, PCO2 levels similarly increased in the blood and extraembryonic fluids. The pH of the blood and amnionic fluid remained approximately constant while the chorioallantoic fluid became progressively acidic. Increases of amnionic fluid and blood HCO-3 indicated that respiartory compensation processes regulate pH. In addition, the disappearance of chorioallantoic fluid HCO-3 suggested that reabsorptive processes may conserve these ions and contribute them to the amnionic fluid by either a direct transfer through the amnioallantoic membrane or by way of the chorioallantoic vascular system.", "contents": "Gas exchange and acid-base regulation in the blood and extraembryonic fluids of the developing chicken embryo. Measurements of pH, PCO2, PO2 and total CO2 were recorded simultaneously in samples of chorioallantoic fluid, amnionic fluid and blood of the chorioallantoic artery from chicken embryos on days 8, 10, 12, 14, 16, 17 and 18 of incubation. During the incubation period studied, PCO2 levels similarly increased in the blood and extraembryonic fluids. The pH of the blood and amnionic fluid remained approximately constant while the chorioallantoic fluid became progressively acidic. Increases of amnionic fluid and blood HCO-3 indicated that respiartory compensation processes regulate pH. In addition, the disappearance of chorioallantoic fluid HCO-3 suggested that reabsorptive processes may conserve these ions and contribute them to the amnionic fluid by either a direct transfer through the amnioallantoic membrane or by way of the chorioallantoic vascular system."}
{"id": "PMID:21443", "title": "Relationship between gastro-oesophageal acid reflux, basal gastro-oesophageal sphincter pressure, and gastric acid secretion.", "content": "Twelve-hour continuous pH-recording at the distal end of the oesophagus and measurement of basal gastro-oesophageal sphincter pressure with perfused catheters were carried out in 108 subjects. Fasting gastric secretion, basal secretion, and maximal acid secretion after subcutaneous injection of 6 microgram pentagastrin/kg bodyweight were determined additionally in some of the subjects. There was a significant inverse correlation between the results of continuous pH-recording and basal gastro-oesophageal sphincter pressure, which confirms the relationship between low sphincter pressure and gastro-oesophageal acid reflux. Furthermore, there was a significant direct correlation between the results of continuous pH-recording and the volume of basal secretion and the basal acid output. These findings emphasize the significance of gastric acid secretion for the results of continuous pH-recording. As reflux-preventive surgery may elicit alterations in the variables of acid secretion, the results of continuous pH-recording do not allow conclusions to be drawn with regard to the effectiveness of a surgically established gastro-oesophageal barrier.", "contents": "Relationship between gastro-oesophageal acid reflux, basal gastro-oesophageal sphincter pressure, and gastric acid secretion. Twelve-hour continuous pH-recording at the distal end of the oesophagus and measurement of basal gastro-oesophageal sphincter pressure with perfused catheters were carried out in 108 subjects. Fasting gastric secretion, basal secretion, and maximal acid secretion after subcutaneous injection of 6 microgram pentagastrin/kg bodyweight were determined additionally in some of the subjects. There was a significant inverse correlation between the results of continuous pH-recording and basal gastro-oesophageal sphincter pressure, which confirms the relationship between low sphincter pressure and gastro-oesophageal acid reflux. Furthermore, there was a significant direct correlation between the results of continuous pH-recording and the volume of basal secretion and the basal acid output. These findings emphasize the significance of gastric acid secretion for the results of continuous pH-recording. As reflux-preventive surgery may elicit alterations in the variables of acid secretion, the results of continuous pH-recording do not allow conclusions to be drawn with regard to the effectiveness of a surgically established gastro-oesophageal barrier."}
{"id": "PMID:21444", "title": "Gastro-oesophageal acid reflux in patients with symptomatic hiatus hernia and effect of a modified Belsey MK IV repair on acid reflux.", "content": "Twelve-hour continuous recording of pH at the distal end of the oesophagus was carried out in 59 patients with sliding hiatus hernia and symptoms suggestive of gastro-oesophageal reflux, and the results were compared with those obtained in normal subjects. Mean duration of pH less than or equal to 2.3, pH less than or equal to 3, pH less than or equal to 4 and pH less than or equal to 5, expressed in percentages of the total time of recording, was longer in patients than in normal subjects. There was no difference in mean number of reflux episodes between patients and normal subjects. The clearest separation between the two groups was obtained by the variable 'duration of pH less than or equal to 5'. Irrespective of the variable used, the results did not seem to be related to the degree of severity of the symptoms. Individual sensitivity of the oesophageal mucosa, the content of bilious components in the refluxed material, and the semi-quantitative character of the investigation may, in part, account for the results. Furthermore, the same investigation was carried out before and three months after a modified Belsey MK IV repair in 39 patients with hiatus hernia and symptoms indicating surgical treatment. The operation was followed by a reduction in the tendency to acid reflux, probably as a result of an increase in the competence of the gastro-oesophageal region.", "contents": "Gastro-oesophageal acid reflux in patients with symptomatic hiatus hernia and effect of a modified Belsey MK IV repair on acid reflux. Twelve-hour continuous recording of pH at the distal end of the oesophagus was carried out in 59 patients with sliding hiatus hernia and symptoms suggestive of gastro-oesophageal reflux, and the results were compared with those obtained in normal subjects. Mean duration of pH less than or equal to 2.3, pH less than or equal to 3, pH less than or equal to 4 and pH less than or equal to 5, expressed in percentages of the total time of recording, was longer in patients than in normal subjects. There was no difference in mean number of reflux episodes between patients and normal subjects. The clearest separation between the two groups was obtained by the variable 'duration of pH less than or equal to 5'. Irrespective of the variable used, the results did not seem to be related to the degree of severity of the symptoms. Individual sensitivity of the oesophageal mucosa, the content of bilious components in the refluxed material, and the semi-quantitative character of the investigation may, in part, account for the results. Furthermore, the same investigation was carried out before and three months after a modified Belsey MK IV repair in 39 patients with hiatus hernia and symptoms indicating surgical treatment. The operation was followed by a reduction in the tendency to acid reflux, probably as a result of an increase in the competence of the gastro-oesophageal region."}
{"id": "PMID:21446", "title": "Anti-parental lymphocyte reactions in neonatal F1 hybrid rats.", "content": "The subpopulation of parental-strain lymphocytes responsible for the recognition of a particular F1 hybrid strain as foreign has been shown to be subject to specific, reversible inactivation after its injection into neonatal rats of that F1 hybrid strain. Neonates born to mothers that were syngeneic with the parental-strain lymphocytes under test acquired the capacity to inactivate these lymphocytes at an earlier age than did the genotypically identical reciprocal F1 hybrids. Neonates had little capacity to inactivate completely allogeneic lymphocytes. It is inferred from the difference in behavior between reciprocal F1 hybrids that the augmented ability to inactivate anti-F1 hybrid maternal-strain lymphocytes follows exposure to such cells in utero and to antibodies with anti-F1 hybrid activity in colostrum. Specific inactivation of those marauding maternal lymphocytes with anti-fetal activity is envisaged as an important means of protection of the fetus from immunological attack by the mother. On the basis of the results presented in this and the preceding paper, it has been proposed that many of the sequelae of the transfer of immunocompetent parental-strain cells to F1 hybrid animals result not from graft anti-host activity but from an F1 hybrid anti-parental lymphocyte response that has eluded normal regulatory mechanisms. These experiments also raise the possibility that regulation of auto-immune responses may be achieved by the inactivation of lymphocytes with anti-self reactivity by other lymphocytes that respond to the recognition structure required for such reactivity.", "contents": "Anti-parental lymphocyte reactions in neonatal F1 hybrid rats. The subpopulation of parental-strain lymphocytes responsible for the recognition of a particular F1 hybrid strain as foreign has been shown to be subject to specific, reversible inactivation after its injection into neonatal rats of that F1 hybrid strain. Neonates born to mothers that were syngeneic with the parental-strain lymphocytes under test acquired the capacity to inactivate these lymphocytes at an earlier age than did the genotypically identical reciprocal F1 hybrids. Neonates had little capacity to inactivate completely allogeneic lymphocytes. It is inferred from the difference in behavior between reciprocal F1 hybrids that the augmented ability to inactivate anti-F1 hybrid maternal-strain lymphocytes follows exposure to such cells in utero and to antibodies with anti-F1 hybrid activity in colostrum. Specific inactivation of those marauding maternal lymphocytes with anti-fetal activity is envisaged as an important means of protection of the fetus from immunological attack by the mother. On the basis of the results presented in this and the preceding paper, it has been proposed that many of the sequelae of the transfer of immunocompetent parental-strain cells to F1 hybrid animals result not from graft anti-host activity but from an F1 hybrid anti-parental lymphocyte response that has eluded normal regulatory mechanisms. These experiments also raise the possibility that regulation of auto-immune responses may be achieved by the inactivation of lymphocytes with anti-self reactivity by other lymphocytes that respond to the recognition structure required for such reactivity."}
{"id": "PMID:21448", "title": "Sensitization of contracted tracheal smooth muscle to beta-adrenergic spasmolysis by subthreshold doses of papaverine.", "content": "In certain cases beta-adrenergic substances cause little or no relaxation of tracheal or bronchiolar smooth muscles contracted by spasmogenic mediators. This phenomenon is explained on the basis of the model of functional antagonism, with the suppositions that the spasmogenic system has a reserve and the spasmogen concentrations are much higher than the concentration which would cause a just-maximal contraction. If this is correct, the model predicts that it should be possible to restore the effectiveness of the beta-adrenergic spasmolytics with low doses of a non-competitive (metactoid) spasmolytic, provided that this substance acts by depressing the subeffect curve. Such a metactoid antagonist should cause the desired result in subthreshold concentrations, i.e. concentrations which as such do not cause relaxation of the contracted muscles. In a series of experiments on the isolated tracheal chain of the guinea-pig the results agreed with this expectation. This provides additional proof for the model of functional interaction and suggests that the combination of beta-adrenergics with low doses of a metactoid spasmolytic may be of clinical interest.", "contents": "Sensitization of contracted tracheal smooth muscle to beta-adrenergic spasmolysis by subthreshold doses of papaverine. In certain cases beta-adrenergic substances cause little or no relaxation of tracheal or bronchiolar smooth muscles contracted by spasmogenic mediators. This phenomenon is explained on the basis of the model of functional antagonism, with the suppositions that the spasmogenic system has a reserve and the spasmogen concentrations are much higher than the concentration which would cause a just-maximal contraction. If this is correct, the model predicts that it should be possible to restore the effectiveness of the beta-adrenergic spasmolytics with low doses of a non-competitive (metactoid) spasmolytic, provided that this substance acts by depressing the subeffect curve. Such a metactoid antagonist should cause the desired result in subthreshold concentrations, i.e. concentrations which as such do not cause relaxation of the contracted muscles. In a series of experiments on the isolated tracheal chain of the guinea-pig the results agreed with this expectation. This provides additional proof for the model of functional interaction and suggests that the combination of beta-adrenergics with low doses of a metactoid spasmolytic may be of clinical interest."}
{"id": "PMID:21449", "title": "[Intermittent positive pressure breathing (IPPB) with respirators in home nursing].", "content": "29 patients using a home respirator have been studied. Management of the respirator and inhalation were correct in 86%. Bacteriologic contamination in home treatment poses few problems. Blood gases and spirometric lung function tests do not demonstrate amelioration but show stabilization in long term treatment. Costs are high. Nevertheless, this treatment is indicated in certain carefully selected patients. Follow-up checks are essential.", "contents": "[Intermittent positive pressure breathing (IPPB) with respirators in home nursing]. 29 patients using a home respirator have been studied. Management of the respirator and inhalation were correct in 86%. Bacteriologic contamination in home treatment poses few problems. Blood gases and spirometric lung function tests do not demonstrate amelioration but show stabilization in long term treatment. Costs are high. Nevertheless, this treatment is indicated in certain carefully selected patients. Follow-up checks are essential."}
{"id": "PMID:21451", "title": "The white cloud. The changing pattern of hematologic research as exemplified by studies of oxygen transport.", "content": "Medical research has become an integral part of governmental health care systems. As a consequence of this subsidization, its resources are far greater, while its activities have become more directly responsible to the perceived needs of the people. Clinical investigation in particular has been affected by this adjustment, and its decreasing role in the total program needs scrutiny. Progress in our understanding of oxygen transport is reviewed as an example of the capacity of today's scientific community to explore and develop new areas of knowledge.", "contents": "The white cloud. The changing pattern of hematologic research as exemplified by studies of oxygen transport. Medical research has become an integral part of governmental health care systems. As a consequence of this subsidization, its resources are far greater, while its activities have become more directly responsible to the perceived needs of the people. Clinical investigation in particular has been affected by this adjustment, and its decreasing role in the total program needs scrutiny. Progress in our understanding of oxygen transport is reviewed as an example of the capacity of today's scientific community to explore and develop new areas of knowledge."}
{"id": "PMID:21452", "title": "Deuterolysis of amino acid precursors: evidence for hydrogen cyanide polymers as protein ancestors.", "content": "Deuterolysis experiments suggest that hydrogen cyanide polymers rather than aminoacetonitriles are major precursors of alpha-amino acids obtained from spark reactions and other studies on chemical evolution. These results are consistent with the hypothesis that the original heteropolypeptides on the earth were synthesized spontaneously from hydrogen cyanide and water without the intervening formation of alpha-amino acids.", "contents": "Deuterolysis of amino acid precursors: evidence for hydrogen cyanide polymers as protein ancestors. Deuterolysis experiments suggest that hydrogen cyanide polymers rather than aminoacetonitriles are major precursors of alpha-amino acids obtained from spark reactions and other studies on chemical evolution. These results are consistent with the hypothesis that the original heteropolypeptides on the earth were synthesized spontaneously from hydrogen cyanide and water without the intervening formation of alpha-amino acids."}
{"id": "PMID:21453", "title": "Flurazepam effects on slow-wave sleep: stage 4 suppressed but number of delta waves constant.", "content": "Repeated administration of flurazepam reduced stage 4 sleep (high delta-wave concentration) but produced a greater increase in stage 2 duration so that total sleep time was increased. Computer analysis revealed that the increased amount of stage 2 (low delta-wave concentration) sleep provided a number and duration of delta waves sufficient to offset the loss of delta activity in stage 4. However, the amplitude of the average delta wave was reduced. These results demonstrate the value of direct quantification of delta-wave activity, the variable that underlies visual classification of slow-wave sleep into stages 2 to 4. They also give rise to new hypotheses regarding the relative absence of side effects in spite of profound stage 4 suppression by flurazepam and the mechanisms by which total sleep time is increased by this drug.", "contents": "Flurazepam effects on slow-wave sleep: stage 4 suppressed but number of delta waves constant. Repeated administration of flurazepam reduced stage 4 sleep (high delta-wave concentration) but produced a greater increase in stage 2 duration so that total sleep time was increased. Computer analysis revealed that the increased amount of stage 2 (low delta-wave concentration) sleep provided a number and duration of delta waves sufficient to offset the loss of delta activity in stage 4. However, the amplitude of the average delta wave was reduced. These results demonstrate the value of direct quantification of delta-wave activity, the variable that underlies visual classification of slow-wave sleep into stages 2 to 4. They also give rise to new hypotheses regarding the relative absence of side effects in spite of profound stage 4 suppression by flurazepam and the mechanisms by which total sleep time is increased by this drug."}
{"id": "PMID:21455", "title": "Repeat myocardial revascularization for uncontrollable angina after occlusion of prior aortocoronary bypass.", "content": "Twelve patients at Emory University Hospital have had repeat myocardial revascularization for recurrent, uncontrollable, disabling angina pectoris after previous coronary artery bypass grafts. The interval betweeen initial bypass procedure and reoperation ranged from six weeks to six years. The native coronary circulation remained unchanged in six, had developed additional proximal (left main) obstruction in four, and had advanced stenosis at the site of former anastomosis in three. Repeat revascularization consisted of new vein graft construction in eight and vein and internal mammary artery graft in four, with an average of 1.9 grafts per patient. There were no deaths. Seven of 12 patients (60%) are now asymptomatic and three of 12 (25%) are significantly improved. Patency of new grafts studied by elective repeat coronary angiography in six patients showed patency of all grafts to the left anterior descending artery and four of six grafts to other vessels. Analysis of the initial graft closures, method for selecting patients to undergo a second procedure, and operative technics believed important in safety of reoperation and avoidance of repeat early graft occlusion are presented.", "contents": "Repeat myocardial revascularization for uncontrollable angina after occlusion of prior aortocoronary bypass. Twelve patients at Emory University Hospital have had repeat myocardial revascularization for recurrent, uncontrollable, disabling angina pectoris after previous coronary artery bypass grafts. The interval betweeen initial bypass procedure and reoperation ranged from six weeks to six years. The native coronary circulation remained unchanged in six, had developed additional proximal (left main) obstruction in four, and had advanced stenosis at the site of former anastomosis in three. Repeat revascularization consisted of new vein graft construction in eight and vein and internal mammary artery graft in four, with an average of 1.9 grafts per patient. There were no deaths. Seven of 12 patients (60%) are now asymptomatic and three of 12 (25%) are significantly improved. Patency of new grafts studied by elective repeat coronary angiography in six patients showed patency of all grafts to the left anterior descending artery and four of six grafts to other vessels. Analysis of the initial graft closures, method for selecting patients to undergo a second procedure, and operative technics believed important in safety of reoperation and avoidance of repeat early graft occlusion are presented."}
{"id": "PMID:21457", "title": "Minocycline treatment failure in pneumonia caused by minocycline-sensitive Streptococcus pneumoniae.", "content": "A previously healthy 23-year-old white woman had fulminant pneumococcal pneumonia complicated by empyema and bilateral pneumothoraces. Despite early treatment with the recommended doses of minocycline, the disease progressed. The S pneumoniae isolate was resistant to a 30microgram tetracycline disk and showed an MIC of 3.13microgram/ml for minocycline and 12.5 microgram/ml for tetracycline; these levels are considered by the manufacturer to indicate sensitivity to minocycline and intermediate sensitivity to tetracycline. The tetracyclines, including minocycline, should not be used to treat bacterial pneumonia since resistant strains of pneumococci are not uncommon and inffective treatment can lead to rapid progression of the infection. This case suggests that the levels of minocycline considered to indicate sensitivity in vitro be reassessed.", "contents": "Minocycline treatment failure in pneumonia caused by minocycline-sensitive Streptococcus pneumoniae. A previously healthy 23-year-old white woman had fulminant pneumococcal pneumonia complicated by empyema and bilateral pneumothoraces. Despite early treatment with the recommended doses of minocycline, the disease progressed. The S pneumoniae isolate was resistant to a 30microgram tetracycline disk and showed an MIC of 3.13microgram/ml for minocycline and 12.5 microgram/ml for tetracycline; these levels are considered by the manufacturer to indicate sensitivity to minocycline and intermediate sensitivity to tetracycline. The tetracyclines, including minocycline, should not be used to treat bacterial pneumonia since resistant strains of pneumococci are not uncommon and inffective treatment can lead to rapid progression of the infection. This case suggests that the levels of minocycline considered to indicate sensitivity in vitro be reassessed."}
{"id": "PMID:21458", "title": "Observation on the reduction of the prevalence of malayan filariasis in Chumphon Province of South Thailand.", "content": "Further studies on malayan filariasis were made at Bangluke canton of Chumphon province of South Thailand, where mass drug treatment was not applied. It was found after 9 years that there was a marked reduction in filariasis in the area. The filariasis infection rate being decreased from 14.1 to 1.9 per cent, the microfilarial rate from 10.8 to 0.9 per cent, and the elephantiasis rate from 3.3 to 1.0 per cent, and the mean microfilarial density among positive cases being decreased from 27.6 to 6.6 per 20 c.mm blood. Dissection of 1,893 Mansonia mosquitoes revealed the finding of only stage I and stage II larvae of B. malayi in seven M. annulifera and M. indiana. The reduction in the filariasis infection was assumed to be due to the interruption of transmission of filariasis cycle in the mosquitoes resulting from DDT spraying operation of the Malaria Eradication Programme of the Thai Government. There were also some positive cases moving out of the area. The rural development programme of the Thai Government also played another important role in the reduction in the prevalence of malayan filariasis in this area.", "contents": "Observation on the reduction of the prevalence of malayan filariasis in Chumphon Province of South Thailand. Further studies on malayan filariasis were made at Bangluke canton of Chumphon province of South Thailand, where mass drug treatment was not applied. It was found after 9 years that there was a marked reduction in filariasis in the area. The filariasis infection rate being decreased from 14.1 to 1.9 per cent, the microfilarial rate from 10.8 to 0.9 per cent, and the elephantiasis rate from 3.3 to 1.0 per cent, and the mean microfilarial density among positive cases being decreased from 27.6 to 6.6 per 20 c.mm blood. Dissection of 1,893 Mansonia mosquitoes revealed the finding of only stage I and stage II larvae of B. malayi in seven M. annulifera and M. indiana. The reduction in the filariasis infection was assumed to be due to the interruption of transmission of filariasis cycle in the mosquitoes resulting from DDT spraying operation of the Malaria Eradication Programme of the Thai Government. There were also some positive cases moving out of the area. The rural development programme of the Thai Government also played another important role in the reduction in the prevalence of malayan filariasis in this area."}
{"id": "PMID:21459", "title": "Anaesthetic induction and maintenance with flunitrazepam.", "content": "Flunitrazepam (Rohypnol) was investigated as an intravenous induction agent for dental procedures in 15 patients in a private anaesthetic practice. During this study it was noted that the normal halothane requirement could be reduced substantially. A second study to investigate this new phenomenon was done on 50 patients who underwent major surgery. The results indicate that adequate anaesthesia can be maintained with flunitrazepam.", "contents": "Anaesthetic induction and maintenance with flunitrazepam. Flunitrazepam (Rohypnol) was investigated as an intravenous induction agent for dental procedures in 15 patients in a private anaesthetic practice. During this study it was noted that the normal halothane requirement could be reduced substantially. A second study to investigate this new phenomenon was done on 50 patients who underwent major surgery. The results indicate that adequate anaesthesia can be maintained with flunitrazepam."}
{"id": "PMID:21461", "title": "Blood viscosity in modern medicine.", "content": "The understanding and measurement of blood viscosity play an important part in mordern medicine. The basic principles and relevances of fluid viscosity are discussed. Factors which alter viscosity include shear rate, haematocrit, erythrocyte deformability, internal fluidity, pH, plasma proteins, temperature, osmolality, lipids and leucocytes. In vivo changes in vascular architecture are thought to influence blood viscosity. Some of the clinical conditions in which viscosity is important are described. Hyperviscosity should be treated before complications arise.", "contents": "Blood viscosity in modern medicine. The understanding and measurement of blood viscosity play an important part in mordern medicine. The basic principles and relevances of fluid viscosity are discussed. Factors which alter viscosity include shear rate, haematocrit, erythrocyte deformability, internal fluidity, pH, plasma proteins, temperature, osmolality, lipids and leucocytes. In vivo changes in vascular architecture are thought to influence blood viscosity. Some of the clinical conditions in which viscosity is important are described. Hyperviscosity should be treated before complications arise."}
{"id": "PMID:21462", "title": "Fertility in undescended testes.", "content": "Since 1956 many children with undescended testes have been treated at the Red Cross War Memorial Children's Hospital in Cape Town, and in this article the conesequent degree of fertility achieved by orchidopexy, the method of treatment, is appraised. In 567 children the condition was unilateral, and in 202 it was bilateral. Assessment of potential fertility in 76 unilateral and in 29 bilateral cases was mainly by semen analysis; the average age of the youths at the time of the examination was 19 years, and parenthood was therefore regarded as an unsuitable criterion for assessment. Four hundred and ninety-two youths had their condition reviewed, and the condition of 587 testes was assessed. The anatomical state of the testes was ascertained to help in the assessment, but also, and of greater importance, to obtain evidence of the usefulness of orchidopexy for cosmetic or psychological benefit. Biopsy of the affected testes, carried out in some, proved to be nor more informative than the anatomical appraisal, with regard to spermatogenesis. Two useful facts emerged from the study. About 10% of bilateral undescended testes are capable of normal spermatogenesis after orchidopexy, and 65% are sterile, while the fertility of persons with unilateral undescended testis is impaired, 28% having little hope of paternity, and 4% no hope at all.", "contents": "Fertility in undescended testes. Since 1956 many children with undescended testes have been treated at the Red Cross War Memorial Children's Hospital in Cape Town, and in this article the conesequent degree of fertility achieved by orchidopexy, the method of treatment, is appraised. In 567 children the condition was unilateral, and in 202 it was bilateral. Assessment of potential fertility in 76 unilateral and in 29 bilateral cases was mainly by semen analysis; the average age of the youths at the time of the examination was 19 years, and parenthood was therefore regarded as an unsuitable criterion for assessment. Four hundred and ninety-two youths had their condition reviewed, and the condition of 587 testes was assessed. The anatomical state of the testes was ascertained to help in the assessment, but also, and of greater importance, to obtain evidence of the usefulness of orchidopexy for cosmetic or psychological benefit. Biopsy of the affected testes, carried out in some, proved to be nor more informative than the anatomical appraisal, with regard to spermatogenesis. Two useful facts emerged from the study. About 10% of bilateral undescended testes are capable of normal spermatogenesis after orchidopexy, and 65% are sterile, while the fertility of persons with unilateral undescended testis is impaired, 28% having little hope of paternity, and 4% no hope at all."}
{"id": "PMID:21463", "title": "Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells: I. Isolation of a mutant defective in the early steps of de novo pyrimidine synthesis.", "content": "The isolation and characterization of a new mutant of Chinese hamster ovary cells is described. This mutant, Urd-A, shows an absolute requirement for exogenously added pyrimidines for growth. Complementation analysis indicates that the lesion in this mutant is recessive. Revertants can be isolated at frequencies suggesting that it is a single gene alteration. Biochemical analysis of cell-free extracts of CHO-K1 (Urd+) and Urd-A revealed that Urd-A possesses no more than 10% of wild-type levels of carbamyl phosphate synthetase (EC 2.7.2.9) activity, no more than 1% of wild-type levels of aspartate transcarbamylase (EC 1.2.3.2) activity, and undetectable levels of dihydroorotase (EC 3.5.2.3) activity. Thus, this mutant appears simultaneously to possess marked or complete deficiencies in the activities of the first three enzymes of pyrimidine biosynthesis. Activities of the other enzymes of the pathway appear normal. The use of this mutant for biochemical-genetic studies of pyrimidine biosynthesis is discussed.", "contents": "Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells: I. Isolation of a mutant defective in the early steps of de novo pyrimidine synthesis. The isolation and characterization of a new mutant of Chinese hamster ovary cells is described. This mutant, Urd-A, shows an absolute requirement for exogenously added pyrimidines for growth. Complementation analysis indicates that the lesion in this mutant is recessive. Revertants can be isolated at frequencies suggesting that it is a single gene alteration. Biochemical analysis of cell-free extracts of CHO-K1 (Urd+) and Urd-A revealed that Urd-A possesses no more than 10% of wild-type levels of carbamyl phosphate synthetase (EC 2.7.2.9) activity, no more than 1% of wild-type levels of aspartate transcarbamylase (EC 1.2.3.2) activity, and undetectable levels of dihydroorotase (EC 3.5.2.3) activity. Thus, this mutant appears simultaneously to possess marked or complete deficiencies in the activities of the first three enzymes of pyrimidine biosynthesis. Activities of the other enzymes of the pathway appear normal. The use of this mutant for biochemical-genetic studies of pyrimidine biosynthesis is discussed."}
{"id": "PMID:21467", "title": "[Veterinary and clinical experience of the use of a beta2-receptor-stimulating sympathicomimetic agent (NAB 365) in horses with respiratory discase (author's transl)].", "content": "The manufacturers state that NAB 365 is a beta2-receptor-stimulating sympathicomimetic agent. According to the medical literature it combines a bronchial antispasmodic effect with certain bronchia secretolytic properties and has few untoward side-effects on, for instance, the heart and intestine. The effectiveness of administration of NAB 365 in horses with chronic or acute respiratory disease was tested in the Department of Veterinary Internal medicine in Utrecht. NAB 365 administered at a dosage of 0.8 gamma/kg, of body weight was found to have a marked bronchodilative effect in horses. There was also evidence of a bronchialsecretolytic effect. NAB 365 has a beneficial effect on respiration. At a dosage of 0.8 gamma/kg of body weight, twice daily, there are few side-effects, even when administration is continued for a fortnight. The clinical effect on respiration continued practically throughout the day.", "contents": "[Veterinary and clinical experience of the use of a beta2-receptor-stimulating sympathicomimetic agent (NAB 365) in horses with respiratory discase (author's transl)]. The manufacturers state that NAB 365 is a beta2-receptor-stimulating sympathicomimetic agent. According to the medical literature it combines a bronchial antispasmodic effect with certain bronchia secretolytic properties and has few untoward side-effects on, for instance, the heart and intestine. The effectiveness of administration of NAB 365 in horses with chronic or acute respiratory disease was tested in the Department of Veterinary Internal medicine in Utrecht. NAB 365 administered at a dosage of 0.8 gamma/kg, of body weight was found to have a marked bronchodilative effect in horses. There was also evidence of a bronchialsecretolytic effect. NAB 365 has a beneficial effect on respiration. At a dosage of 0.8 gamma/kg of body weight, twice daily, there are few side-effects, even when administration is continued for a fortnight. The clinical effect on respiration continued practically throughout the day."}
{"id": "PMID:21469", "title": "Antibacterial activity detected in duodenal juice.", "content": "Antibacterial activity could be detected in bacterium-negative duodenal juice from 3 patients, whereas it was not detected in bacterium-positive duodenal juice from other 3 patients. The follow-up study revealed that appearance of the activity in duodenal juice was just coincident with disappearance of bacteria in duodenal juice. The activity was not influenced by pH of the duodenal juice. These results seem to suggest that some antibacterial activity, different from that of pH, in duodenal juice regulates in some way proliferation of the upper gastrointestinal flora.", "contents": "Antibacterial activity detected in duodenal juice. Antibacterial activity could be detected in bacterium-negative duodenal juice from 3 patients, whereas it was not detected in bacterium-positive duodenal juice from other 3 patients. The follow-up study revealed that appearance of the activity in duodenal juice was just coincident with disappearance of bacteria in duodenal juice. The activity was not influenced by pH of the duodenal juice. These results seem to suggest that some antibacterial activity, different from that of pH, in duodenal juice regulates in some way proliferation of the upper gastrointestinal flora."}
{"id": "PMID:21470", "title": "A rapid fluorometric assay of angiotensin-converting enzyme.", "content": "A rapid, simple and sensitive method is described for the fluorometric assay of angiotesin-converting enzyme using Fluorescamine. The critical factors such as optimal pH, incubation time, chloride ion, and inactivation by EDTA and 8-hydroxyquinoline were examined. The Km value for hippuryl-L-histidyl-L-leucine was 0.5 mM. This method was applied to the assay of angiotensin-converting enzyme in the rat serum and the reproducible values were obtained with a 10 mul of the rat serum.", "contents": "A rapid fluorometric assay of angiotensin-converting enzyme. A rapid, simple and sensitive method is described for the fluorometric assay of angiotesin-converting enzyme using Fluorescamine. The critical factors such as optimal pH, incubation time, chloride ion, and inactivation by EDTA and 8-hydroxyquinoline were examined. The Km value for hippuryl-L-histidyl-L-leucine was 0.5 mM. This method was applied to the assay of angiotensin-converting enzyme in the rat serum and the reproducible values were obtained with a 10 mul of the rat serum."}
{"id": "PMID:21471", "title": "Methylmalonyl-CoA mutase activity of leukocytes in variants and heterozygotes of methylmalonic acidemia.", "content": "An assay method for the methylmalonyl-CoA mutase of leukocytes obtained from 3 ml of blood was established. The enzyme activity which was measured with or without the in vitro addition of 5'-deoxyadenosylcobalamin was found to be of value for the diagnosis of two variants of methylmalonic acidemia (vitamin B12 responsive and unresponsive), and also for the detection of heterozygotes with the vitamin B12 unresponsive type.", "contents": "Methylmalonyl-CoA mutase activity of leukocytes in variants and heterozygotes of methylmalonic acidemia. An assay method for the methylmalonyl-CoA mutase of leukocytes obtained from 3 ml of blood was established. The enzyme activity which was measured with or without the in vitro addition of 5'-deoxyadenosylcobalamin was found to be of value for the diagnosis of two variants of methylmalonic acidemia (vitamin B12 responsive and unresponsive), and also for the detection of heterozygotes with the vitamin B12 unresponsive type."}
{"id": "PMID:21473", "title": "Partial characterization of epididymal 5 alpha reductase in the rat.", "content": "Epididymal 5alpha reductase activity was found distitributed in the crude nuclear fraction (44 percent) and microsomal fraction (41 percent). Spermatozoa contaminating the nuclear preparation accounted for only 3 percent of its activity. There were no regional differences in the distribution of total 5alpha reductase activity. However, the nuclear enzyme was more active in caput than in other regions. Maximal activity was found at pH 6.2 and at 32 degrees C. Both enzymes had an absolute requirement of reduced dinucleotides. The microsomal preparation could only us NADPH while the nuclear enzyme could use NADPH and NADH. The apparent Km for the microsomal preparation was 0.62 +/- 0.05 X 10(-6)M and Vmax was 555 +/- 38 pmoles/mg protein/hour. The nuclear enzyme presented similar values. The reaction was not inhibited by accumulation of product in the medium, but other steroids such as progesterone, epitestosterone (17alpha-hydroxy-4-androsten-3-one) and 3-oxo-4-androstene-17beta-carboxylic acid were potent competitive inhibitors. The reaction was strongly inhibited by Hg, Zn and Cu. The properties of the epididymal reductase are similar to those of the prostatic enzyme.", "contents": "Partial characterization of epididymal 5 alpha reductase in the rat. Epididymal 5alpha reductase activity was found distitributed in the crude nuclear fraction (44 percent) and microsomal fraction (41 percent). Spermatozoa contaminating the nuclear preparation accounted for only 3 percent of its activity. There were no regional differences in the distribution of total 5alpha reductase activity. However, the nuclear enzyme was more active in caput than in other regions. Maximal activity was found at pH 6.2 and at 32 degrees C. Both enzymes had an absolute requirement of reduced dinucleotides. The microsomal preparation could only us NADPH while the nuclear enzyme could use NADPH and NADH. The apparent Km for the microsomal preparation was 0.62 +/- 0.05 X 10(-6)M and Vmax was 555 +/- 38 pmoles/mg protein/hour. The nuclear enzyme presented similar values. The reaction was not inhibited by accumulation of product in the medium, but other steroids such as progesterone, epitestosterone (17alpha-hydroxy-4-androsten-3-one) and 3-oxo-4-androstene-17beta-carboxylic acid were potent competitive inhibitors. The reaction was strongly inhibited by Hg, Zn and Cu. The properties of the epididymal reductase are similar to those of the prostatic enzyme."}
{"id": "PMID:21474", "title": "Oxidative metabolism and de-ethynylation of 17alpha-ethynylestradiol by baboon liver microsomes.", "content": "Incubations of tritiated 17alpha-ethynylestradiol (EE2) with liver explants of baboon and mouse showed the primate species to be more efficient in the removal of the ethynyl group. Liver microsomes from sexually immature male and female baboons were then incubated with tritiated EE2 and estradiol (E2). Each hormone bound irreversibly to the microsomal pellet. Addition of glutathione reduced the irreversible or covalent association. Incubations with E2 demonstrated significant conversion to estrone (E1). The EE2 experiments demonstrated a conversion to estrone only in the presence of an NADPH-generating system, and the addition of SKF-525A reduced the conversion of EE2 to E1. The cleavage reaction appears to be an oxidative event.", "contents": "Oxidative metabolism and de-ethynylation of 17alpha-ethynylestradiol by baboon liver microsomes. Incubations of tritiated 17alpha-ethynylestradiol (EE2) with liver explants of baboon and mouse showed the primate species to be more efficient in the removal of the ethynyl group. Liver microsomes from sexually immature male and female baboons were then incubated with tritiated EE2 and estradiol (E2). Each hormone bound irreversibly to the microsomal pellet. Addition of glutathione reduced the irreversible or covalent association. Incubations with E2 demonstrated significant conversion to estrone (E1). The EE2 experiments demonstrated a conversion to estrone only in the presence of an NADPH-generating system, and the addition of SKF-525A reduced the conversion of EE2 to E1. The cleavage reaction appears to be an oxidative event."}
{"id": "PMID:21478", "title": "[Triggering and regulatory mechanisms of ciliary motion in the ctenophore Bolinopsis. III. Electric excitability and inherent contractility of ciliated cells].", "content": "Rhythmical electrostimulation is able to produce in a tissue strip of Bolinopsis series of beats of combs-plates. However, the beat frequency, within one series, is only poorly controlled by electrical stimuli. Isolated comb-plate cells with a cilium cut off maintain rhythmical contractions stimulated both mechanically and electrically. A lot of microtubules has been found in the apical region of these cells. It is supposed that it is these microtubules, probably together with the associated root filaments, that are responsible for cell motility. Mutual mechanical stimulation of ciliary cells in these motions is, presumably, a signal providing intratissue propagation of metachronal wave.", "contents": "[Triggering and regulatory mechanisms of ciliary motion in the ctenophore Bolinopsis. III. Electric excitability and inherent contractility of ciliated cells]. Rhythmical electrostimulation is able to produce in a tissue strip of Bolinopsis series of beats of combs-plates. However, the beat frequency, within one series, is only poorly controlled by electrical stimuli. Isolated comb-plate cells with a cilium cut off maintain rhythmical contractions stimulated both mechanically and electrically. A lot of microtubules has been found in the apical region of these cells. It is supposed that it is these microtubules, probably together with the associated root filaments, that are responsible for cell motility. Mutual mechanical stimulation of ciliary cells in these motions is, presumably, a signal providing intratissue propagation of metachronal wave."}
{"id": "PMID:21481", "title": "Splenic-gonadal fusion and adrenal cortical rest associated with bilateral cryptorchism.", "content": "A patient with bilateral cryptorchism had ectopic splenic tissue adherent to his left testicle and an adrenal cortical rest adherent to his right testicle. The embrylogic basis for these disorders is discussed and the literature reviewed.", "contents": "Splenic-gonadal fusion and adrenal cortical rest associated with bilateral cryptorchism. A patient with bilateral cryptorchism had ectopic splenic tissue adherent to his left testicle and an adrenal cortical rest adherent to his right testicle. The embrylogic basis for these disorders is discussed and the literature reviewed."}
{"id": "PMID:21482", "title": "Uropharmacology: part VI. Parasympathetic depressants.", "content": "A discussion of the various parasympathetic depressants is presented. Belladonna alkaloids include atropine, the prototype, and scopolamine. Synthetic drugs include quaternary ammonium compounds with antimuscarinic activity such as methantheline, propantheline, and other drugs such as isopropamide, pipenzolate methylbromide, and diphemanil methylsulfate. A miscellaneous class of drugs such as hemicholinium, valethamate, and oxybutynin chloride also possesses parasympathetic depressant activity. The pharmacologic properties and clinical usage of these drugs are discussed.", "contents": "Uropharmacology: part VI. Parasympathetic depressants. A discussion of the various parasympathetic depressants is presented. Belladonna alkaloids include atropine, the prototype, and scopolamine. Synthetic drugs include quaternary ammonium compounds with antimuscarinic activity such as methantheline, propantheline, and other drugs such as isopropamide, pipenzolate methylbromide, and diphemanil methylsulfate. A miscellaneous class of drugs such as hemicholinium, valethamate, and oxybutynin chloride also possesses parasympathetic depressant activity. The pharmacologic properties and clinical usage of these drugs are discussed."}
{"id": "PMID:21483", "title": "[Method of stabilizing ketamine anesthesia].", "content": "The authors eliminated the disavantages of intravenous ketamine anesthesia, interfering with its wide use (hypertension, tachicardia, hypersalivation, diplopia etc.) by means of preliminary ganglionic blockade. Clinical studies of ketamine anesthesis with ganglionic blockade and without the latter illustrated the advantages of the suggested method.", "contents": "[Method of stabilizing ketamine anesthesia]. The authors eliminated the disavantages of intravenous ketamine anesthesia, interfering with its wide use (hypertension, tachicardia, hypersalivation, diplopia etc.) by means of preliminary ganglionic blockade. Clinical studies of ketamine anesthesis with ganglionic blockade and without the latter illustrated the advantages of the suggested method."}
{"id": "PMID:21480", "title": "[Effect of carbonic acid concentration in blood on content of keto-acids and redox state of nicotinamide coenzymes in rabbit tissues].", "content": "A rise in the level of carbonic acid in animal blood at practically unchanged pH causes an increase in the value of free [NAD+]/[NADH] and [NADP+]/[NADPH] ratios in the liver cells cytoplasm. The increase in the oxidizing power of the liver cells cytoplasm is observed against a background of a rise in both the total level of keto-acids in blood and concentration of pyruvate oxaloacetate and alpha-ketoglutarate in the liver and kidneys of animals. The level of lactate, glutamate and citrate in these tissues also grows. The level of ketonic bodies in blood of the animals with a higher concentration of carbonic acid is somewhat lower than that in the animals with a lower concentration of HCO3 and CO2 in blood.", "contents": "[Effect of carbonic acid concentration in blood on content of keto-acids and redox state of nicotinamide coenzymes in rabbit tissues]. A rise in the level of carbonic acid in animal blood at practically unchanged pH causes an increase in the value of free [NAD+]/[NADH] and [NADP+]/[NADPH] ratios in the liver cells cytoplasm. The increase in the oxidizing power of the liver cells cytoplasm is observed against a background of a rise in both the total level of keto-acids in blood and concentration of pyruvate oxaloacetate and alpha-ketoglutarate in the liver and kidneys of animals. The level of lactate, glutamate and citrate in these tissues also grows. The level of ketonic bodies in blood of the animals with a higher concentration of carbonic acid is somewhat lower than that in the animals with a lower concentration of HCO3 and CO2 in blood."}
{"id": "PMID:21486", "title": "Acid elution of blood group antibodies from intact erythrocytes.", "content": "Human IgM and IgG antibodies against blood group antigens (A, B, D, C, c, E, e, Fya, K), autoantibodies and mouse IgM and IgG antibodies against sheep erythrocytes have been eluted from intact human and sheep red cells by glycine-HCl buffer, pH 3.0. The yield of human antibodies was higher with acid than with heat and ether elution, and the contamination of hemoglobin in the eluate was negligible. The acid elution method is very simple and rapid and, therefore, highly suitable for experimental as well as routine immunohematological work.", "contents": "Acid elution of blood group antibodies from intact erythrocytes. Human IgM and IgG antibodies against blood group antigens (A, B, D, C, c, E, e, Fya, K), autoantibodies and mouse IgM and IgG antibodies against sheep erythrocytes have been eluted from intact human and sheep red cells by glycine-HCl buffer, pH 3.0. The yield of human antibodies was higher with acid than with heat and ether elution, and the contamination of hemoglobin in the eluate was negligible. The acid elution method is very simple and rapid and, therefore, highly suitable for experimental as well as routine immunohematological work."}
{"id": "PMID:21484", "title": "[Relationship between glycolysis and pentose cycle intensity and thrombocyte aggregation induced by ADP in man].", "content": "Aggregation of thrombocytes, caused by ADP, affected the rate of anaerobic breakdown of carbohydrates due to inhibition of the glucose degradation, while the rate of lactate formation was not distinctly altered. Content of NAD was decreased simultaneously with an increase in content of NADP; the activity of glucose-6-phosphate dehydrogenase was distinctly increased but the unaltered activity of 6-phosphogluconate dehydrogenase was observed; content of reduced glutathione was increased 15-fold. The activity of NADP-dependent glutathione reductase was increased under effect of ADP; at the same time, the activity of NAD-dependent glutathione reductase did not depend on the diphosphate effect.", "contents": "[Relationship between glycolysis and pentose cycle intensity and thrombocyte aggregation induced by ADP in man]. Aggregation of thrombocytes, caused by ADP, affected the rate of anaerobic breakdown of carbohydrates due to inhibition of the glucose degradation, while the rate of lactate formation was not distinctly altered. Content of NAD was decreased simultaneously with an increase in content of NADP; the activity of glucose-6-phosphate dehydrogenase was distinctly increased but the unaltered activity of 6-phosphogluconate dehydrogenase was observed; content of reduced glutathione was increased 15-fold. The activity of NADP-dependent glutathione reductase was increased under effect of ADP; at the same time, the activity of NAD-dependent glutathione reductase did not depend on the diphosphate effect."}
{"id": "PMID:21489", "title": "[Pathophysiology of lipolysis in human adipose tissue (author's transl)].", "content": "Lipolysis in human adipose tissue was measured as glycerol release in isolated fat cells and in adipose tissue homogenates. In isolated fat cells lipolysis proceeded optimally at pH 7.4, was stimulated 3.5 fold by noradrenaline and was not influenced by serum or protamine. In adipose tissue homogenates lipolysis was stimulated 4 fold by serum. Serum-stimulated lipolytic activity was optimal at pH 8.0, was inhibited by 1 M sodium chloride and protamine and was not influenced by noradrenaline. Lipolytic activity in isolated fat cells is ascribed on the basis of these observations mainly to the action of hormone-sensitive lipase. whereas lipolysis in adipose tissue homogenates in the presence of serum seems to be regulated by lipoprotein lipase. Thus, the lipolytic processes involved in the mobilization of triglycerides from adipose tissue and in the uptake or triglycerides into adipose tissue can be assessed separately, using the two described methods. The re-esterification of FFA, the second pathway in the mobilization of triglycerides, has also been investigated.", "contents": "[Pathophysiology of lipolysis in human adipose tissue (author's transl)]. Lipolysis in human adipose tissue was measured as glycerol release in isolated fat cells and in adipose tissue homogenates. In isolated fat cells lipolysis proceeded optimally at pH 7.4, was stimulated 3.5 fold by noradrenaline and was not influenced by serum or protamine. In adipose tissue homogenates lipolysis was stimulated 4 fold by serum. Serum-stimulated lipolytic activity was optimal at pH 8.0, was inhibited by 1 M sodium chloride and protamine and was not influenced by noradrenaline. Lipolytic activity in isolated fat cells is ascribed on the basis of these observations mainly to the action of hormone-sensitive lipase. whereas lipolysis in adipose tissue homogenates in the presence of serum seems to be regulated by lipoprotein lipase. Thus, the lipolytic processes involved in the mobilization of triglycerides from adipose tissue and in the uptake or triglycerides into adipose tissue can be assessed separately, using the two described methods. The re-esterification of FFA, the second pathway in the mobilization of triglycerides, has also been investigated."}
{"id": "PMID:21485", "title": "[Specificity of glutamine metabolism in pre-tumorous diseases and cancer of the human stomach].", "content": "Content of free glutamine and the activity of glutamine synthetase and glutamine transaminase were studied in practically healthy persons and in patients with chronic atrophic gastritis, ulcerous disease, polyposis and with gastric carcinoma. The enzymatic activity was estimated in the areas of ulcerous impairment, of polypous vegetation of malignant neoplasm as well as in mucous membrane out of the impaired zone and in whole blood of all the patients studied. The tissues for biochemical tests were obtained by the directed gastrobiopsy. Content of glutamine was decreased in blood of patients with gastric carcinoma and increased in mucous membrane adjacent to the malignant tissue. Occurrence of the glutamine transaminase activity in the tissue areas studied was due to the specific glutamine metabolism during pretumoral diseases and gastric carcinoma, whereas the unimpaired gastric mucosa did not have the distinct enzymatic activity.", "contents": "[Specificity of glutamine metabolism in pre-tumorous diseases and cancer of the human stomach]. Content of free glutamine and the activity of glutamine synthetase and glutamine transaminase were studied in practically healthy persons and in patients with chronic atrophic gastritis, ulcerous disease, polyposis and with gastric carcinoma. The enzymatic activity was estimated in the areas of ulcerous impairment, of polypous vegetation of malignant neoplasm as well as in mucous membrane out of the impaired zone and in whole blood of all the patients studied. The tissues for biochemical tests were obtained by the directed gastrobiopsy. Content of glutamine was decreased in blood of patients with gastric carcinoma and increased in mucous membrane adjacent to the malignant tissue. Occurrence of the glutamine transaminase activity in the tissue areas studied was due to the specific glutamine metabolism during pretumoral diseases and gastric carcinoma, whereas the unimpaired gastric mucosa did not have the distinct enzymatic activity."}
{"id": "PMID:21494", "title": "[On characterization of lipoxygenase from barley (author's transl)].", "content": "Lipoxygenase from brewing barley of Nordbaden has optimum activity at alkaline pH and predominantly forms 9-hydroperoxy-10-trans, 12-cis-octadecadienoic acid (9-LHPO) from linoleic acid. While at pH 7 90% 9-LHPO is produced, its proportions drops during incubation at more alkaline pH (pH 7,75) to 70%. This positional specifity is not caused by isoenzymes. While linoleic acid methylester is converted only to a lesser degree, trilinolein is not accepted as substrate.", "contents": "[On characterization of lipoxygenase from barley (author's transl)]. Lipoxygenase from brewing barley of Nordbaden has optimum activity at alkaline pH and predominantly forms 9-hydroperoxy-10-trans, 12-cis-octadecadienoic acid (9-LHPO) from linoleic acid. While at pH 7 90% 9-LHPO is produced, its proportions drops during incubation at more alkaline pH (pH 7,75) to 70%. This positional specifity is not caused by isoenzymes. While linoleic acid methylester is converted only to a lesser degree, trilinolein is not accepted as substrate."}
{"id": "PMID:21495", "title": "[The idiopathic respiratory distress syndrome from the obstetrical point of view].", "content": "Frequency of idiopathic respiratory distress syndrome (IRDS) of low birth weight children was examined over 15 years (1960 to 1975) in the Frauenklinik of the Ernst-Moritz-Arndt-University of Greifswald. Possible pathogenetic risk factors were proofed. The validity of the Apgar-score and blood gas analyses for the development of IRDS was investigated. Finally, the coincidence between mode of delivery, early rupture of membrane and imminent intrauterine infection in relation to the frequency of IRDS was shown.", "contents": "[The idiopathic respiratory distress syndrome from the obstetrical point of view]. Frequency of idiopathic respiratory distress syndrome (IRDS) of low birth weight children was examined over 15 years (1960 to 1975) in the Frauenklinik of the Ernst-Moritz-Arndt-University of Greifswald. Possible pathogenetic risk factors were proofed. The validity of the Apgar-score and blood gas analyses for the development of IRDS was investigated. Finally, the coincidence between mode of delivery, early rupture of membrane and imminent intrauterine infection in relation to the frequency of IRDS was shown."}
{"id": "PMID:21496", "title": "[Induction of labor with prostaglandin F 2 alpha (a comparative study using oxytocin and prostaglandin)].", "content": "The authors investigated the effectiveness of prostaglandin F2alpha administered by intravenous drop infusion to induce labour. They compared their results with those obtained in oxytocin-induced labour. They determined that prostaglandin F2alpha can without any danger be administered in the induction of labour. The process of labour and the ensuing results indicate that prostaglandin is less of a burden to the uteroplacental circulation. In administering either of the two drugs, the authors deem the principle of applying the \"smallest\" dose important.", "contents": "[Induction of labor with prostaglandin F 2 alpha (a comparative study using oxytocin and prostaglandin)]. The authors investigated the effectiveness of prostaglandin F2alpha administered by intravenous drop infusion to induce labour. They compared their results with those obtained in oxytocin-induced labour. They determined that prostaglandin F2alpha can without any danger be administered in the induction of labour. The process of labour and the ensuing results indicate that prostaglandin is less of a burden to the uteroplacental circulation. In administering either of the two drugs, the authors deem the principle of applying the \"smallest\" dose important."}
{"id": "PMID:21497", "title": "[Behavior of various serum and urinary peptidases in pregnancy].", "content": "The investigations were carried out on activities of leucinearylamidase (LAP) and (GGTP) gammaglutamyltranspeptidase in serum and urine of women with physiological and prolonged pregnancy. The results shown on pathological increase of LAP-activity in serum and increase excretion of both enzymes in to the urine during prolonged pregnancy. These findings may appear very important for the explain of pathomechanism of prolonged pregnancy and diagnostic purpose.", "contents": "[Behavior of various serum and urinary peptidases in pregnancy]. The investigations were carried out on activities of leucinearylamidase (LAP) and (GGTP) gammaglutamyltranspeptidase in serum and urine of women with physiological and prolonged pregnancy. The results shown on pathological increase of LAP-activity in serum and increase excretion of both enzymes in to the urine during prolonged pregnancy. These findings may appear very important for the explain of pathomechanism of prolonged pregnancy and diagnostic purpose."}
{"id": "PMID:21499", "title": "[Relationship between the incidence of neurologic complications following smallpox vaccination and the generation and infectious activity of vaccine from strain L-IVP].", "content": "A strictly controlled epidemiological trial was applied to the study of the incidence of neurological complications in children inoculated with vaccine from the L-IVP strain of the 2nd, 3rd, and 5th passages (generations). To ascertain a possible connection between the neuropathogenicity with the infectious activity the persons vaccinated were divided into 3 groups in accordance with the infectiousness level of the preparation obtained: the I group--3--5-10(8)OOU/ml; the II group--6--8-9-10(8) OOU/ml; the III group over 9-10(8) OOU/ml. The least number of neurological complications was recorded among children primarily inoculated with the vaccine of the 3rd passage with the infectiousness titre of over 9-10(8) OOU/ml.", "contents": "[Relationship between the incidence of neurologic complications following smallpox vaccination and the generation and infectious activity of vaccine from strain L-IVP]. A strictly controlled epidemiological trial was applied to the study of the incidence of neurological complications in children inoculated with vaccine from the L-IVP strain of the 2nd, 3rd, and 5th passages (generations). To ascertain a possible connection between the neuropathogenicity with the infectious activity the persons vaccinated were divided into 3 groups in accordance with the infectiousness level of the preparation obtained: the I group--3--5-10(8)OOU/ml; the II group--6--8-9-10(8) OOU/ml; the III group over 9-10(8) OOU/ml. The least number of neurological complications was recorded among children primarily inoculated with the vaccine of the 3rd passage with the infectiousness titre of over 9-10(8) OOU/ml."}
{"id": "PMID:21500", "title": "[Role of autoimmune processes in the pathogenesis of post-vaccinal lesions of the nervous system].", "content": "Subcutaneous sensitization of guinea pigs with -vaccine, and also an intracardiac injection of smallpox or measles vaccine induced production of brain autoantibodies, whereas subcutaneous or intradermal immunization of the animals with liver viral vaccines was not accompanied by the formation of autoantibodies and development of the pathological processes in the nervous system tissue. tthe greatest changes in the brain tissue in the form of circulatory disturbances and inflammatory-dystrophic phenomena in combination with high autoantibody titres in the blood were noted in intracardiac injection of smallpox vaccine and in subturbancessensitization with AK-Vaccine and the least (short-term circulatory disturbances, transitory signs of serous meningitis and neuron dystrophy against the background of low blood auto anitbody content)--in intracardiac injection of measles vaccine. Administration of live viral vaccines into the circulation of animals against the background of their sensitization with -vaccine led to reduction of blood autoantibody level coinciding in time with the periods of marked pathomorphological changes in the brain tissue.", "contents": "[Role of autoimmune processes in the pathogenesis of post-vaccinal lesions of the nervous system]. Subcutaneous sensitization of guinea pigs with -vaccine, and also an intracardiac injection of smallpox or measles vaccine induced production of brain autoantibodies, whereas subcutaneous or intradermal immunization of the animals with liver viral vaccines was not accompanied by the formation of autoantibodies and development of the pathological processes in the nervous system tissue. tthe greatest changes in the brain tissue in the form of circulatory disturbances and inflammatory-dystrophic phenomena in combination with high autoantibody titres in the blood were noted in intracardiac injection of smallpox vaccine and in subturbancessensitization with AK-Vaccine and the least (short-term circulatory disturbances, transitory signs of serous meningitis and neuron dystrophy against the background of low blood auto anitbody content)--in intracardiac injection of measles vaccine. Administration of live viral vaccines into the circulation of animals against the background of their sensitization with -vaccine led to reduction of blood autoantibody level coinciding in time with the periods of marked pathomorphological changes in the brain tissue."}
{"id": "PMID:21501", "title": "Pseudomonas cytochrome c peroxidase. XIII. pH-denaturation of the enzyme.", "content": "The effect of pH on the oxidized Pseudomonas cytochrome c peroxidase molecule was studied by measuring the peroxidatic activity, the sedimentation velocity, the circular dichroic spectra in the far UV and Soret regions, and the optical absorption spectra of the enzyme in the pH range 2.5-13.0 at a constant ionic strength (micron = 0.1). The enzyme was stable in a narrow pH region, pH 6.0 - 7.4. In the low pH range the gross tertiary structure was observed to change quite simultaneously with the enzymatic activity and secondary structure. The optical absorption spectra indicated that there were no coordinated internal protein liqands in the 6th coordination positions of the heme prosthetic groups at the lowest pH studied. In the high pH range the secondary structure and the protein environment of hemes were observed to remain stable after the tertiary structure had changed and the activity had decreased. According to the optical absorption spectra the 6th internal protein ligands of hemes were retained at the highest pH studied.", "contents": "Pseudomonas cytochrome c peroxidase. XIII. pH-denaturation of the enzyme. The effect of pH on the oxidized Pseudomonas cytochrome c peroxidase molecule was studied by measuring the peroxidatic activity, the sedimentation velocity, the circular dichroic spectra in the far UV and Soret regions, and the optical absorption spectra of the enzyme in the pH range 2.5-13.0 at a constant ionic strength (micron = 0.1). The enzyme was stable in a narrow pH region, pH 6.0 - 7.4. In the low pH range the gross tertiary structure was observed to change quite simultaneously with the enzymatic activity and secondary structure. The optical absorption spectra indicated that there were no coordinated internal protein liqands in the 6th coordination positions of the heme prosthetic groups at the lowest pH studied. In the high pH range the secondary structure and the protein environment of hemes were observed to remain stable after the tertiary structure had changed and the activity had decreased. According to the optical absorption spectra the 6th internal protein ligands of hemes were retained at the highest pH studied."}
{"id": "PMID:21498", "title": "[Interneuronal synapses with electrical and chemical mechanisms of transmission and the evolution of the central nervous system].", "content": "It becomes increasingly evident that not only chemical but also electrotonic synapses are characteristic feature of the vertebrate brain. Experiments carried out on the isolated perfused central nervous system of lampreys and frogs have shown that in cyclostomes spinal motoneurons receive at least 4 different electrotonic inputs: from giant reticulospinal axons, from smaller descending fibers intrinsic to the cord, from primary afferents and ventral roots. In amphibian motoneurons it is possible to identify 3 electrotonically mediated monosynaptic actions: from primary afferents, recurrent, and reticulospinal. The exact mode of transmission of monosynaptic excitation 1a and supraspinal actions in mammals remains to be elucidated. The trends of evolutionary development of synaptic transmissional processes and synaptic organization in vertebrate nervous system are discussed.", "contents": "[Interneuronal synapses with electrical and chemical mechanisms of transmission and the evolution of the central nervous system]. It becomes increasingly evident that not only chemical but also electrotonic synapses are characteristic feature of the vertebrate brain. Experiments carried out on the isolated perfused central nervous system of lampreys and frogs have shown that in cyclostomes spinal motoneurons receive at least 4 different electrotonic inputs: from giant reticulospinal axons, from smaller descending fibers intrinsic to the cord, from primary afferents and ventral roots. In amphibian motoneurons it is possible to identify 3 electrotonically mediated monosynaptic actions: from primary afferents, recurrent, and reticulospinal. The exact mode of transmission of monosynaptic excitation 1a and supraspinal actions in mammals remains to be elucidated. The trends of evolutionary development of synaptic transmissional processes and synaptic organization in vertebrate nervous system are discussed."}
{"id": "PMID:21503", "title": "Correlation of pituitary and testicular responses to stimulation tests in cryptorchid children.", "content": "LH-RH test and HCG stimulation test were performed in 154 cryptorchid boys aged 1 month to 15 years (64 unilateral and 90 bilateral). Basal plasma LH levels and LH response to LH-RH were significantly lower from infancy to early puberty in cryptorchids compared with controls. Basal FSH levels and FSH response to LH-RH were normal. The post-HCG rise of plasma testosterone was reduced until mid-puberty. A significant positive correlation was found between post-HCG testosterone levels and pre- and post-LH-RH levels of LH. This correlation suggests that testicular maldescent and the decreased ability of Leydig cells to respond to a short course of HCG may result from an early defect or a delay of pituitary LH secretion.", "contents": "Correlation of pituitary and testicular responses to stimulation tests in cryptorchid children. LH-RH test and HCG stimulation test were performed in 154 cryptorchid boys aged 1 month to 15 years (64 unilateral and 90 bilateral). Basal plasma LH levels and LH response to LH-RH were significantly lower from infancy to early puberty in cryptorchids compared with controls. Basal FSH levels and FSH response to LH-RH were normal. The post-HCG rise of plasma testosterone was reduced until mid-puberty. A significant positive correlation was found between post-HCG testosterone levels and pre- and post-LH-RH levels of LH. This correlation suggests that testicular maldescent and the decreased ability of Leydig cells to respond to a short course of HCG may result from an early defect or a delay of pituitary LH secretion."}
{"id": "PMID:21504", "title": "Comparison of a new antihistamine HC 20-511 with cyproheptadine (Periactin) in chronic urticaria.", "content": "The effect and tolerance of a new antihistamine, HC 20-511, in daily doses of 2 and 4 mg was compared with cyproheptadine (Periactin) 8 mg daily in 50 cases of chronic urticaria. HC 20-511 4 mg daily proved to be the most effective, rapid and long-lasting. HC 20-511 had less sedative effect than cyproheptadine, but both possessed the same appetite-stimulating effect. However, this was not noted with the smaller dosage of HC 20-511.", "contents": "Comparison of a new antihistamine HC 20-511 with cyproheptadine (Periactin) in chronic urticaria. The effect and tolerance of a new antihistamine, HC 20-511, in daily doses of 2 and 4 mg was compared with cyproheptadine (Periactin) 8 mg daily in 50 cases of chronic urticaria. HC 20-511 4 mg daily proved to be the most effective, rapid and long-lasting. HC 20-511 had less sedative effect than cyproheptadine, but both possessed the same appetite-stimulating effect. However, this was not noted with the smaller dosage of HC 20-511."}
{"id": "PMID:21505", "title": "Action of enflurane (Ethrane) on the neuromusclar block induced by AH 8165 D.", "content": "The neuromuscular block induced by AH 8165 D, a new non-depolarizing muscle relaxant, has been studied in two series of anesthetised patients. All the anesthetics were induced  by Althesin, and intubations performed under local  anesthesia. The first series of 15 patients received only 75% nitrous oxide and 25% oxygen for the first hour of anesthesia. The second series received in addition 1 to 1.5% of enflurane. After an hour all the patients received a single dose of AH 8165 D. Dose-response curves  were established in both series and it was found that without enflurane the ED50 of AH 8165 D was 8.29 mg/m2 and with enflurane 4.07 mg/m2. Therefore enflurane potentiates the action of AH 8165 D by 2.03 times, although it is impossible from this study to indicate precisely how and where enflurane can affect neuromuscular transmission.", "contents": "Action of enflurane (Ethrane) on the neuromusclar block induced by AH 8165 D. The neuromuscular block induced by AH 8165 D, a new non-depolarizing muscle relaxant, has been studied in two series of anesthetised patients. All the anesthetics were induced  by Althesin, and intubations performed under local  anesthesia. The first series of 15 patients received only 75% nitrous oxide and 25% oxygen for the first hour of anesthesia. The second series received in addition 1 to 1.5% of enflurane. After an hour all the patients received a single dose of AH 8165 D. Dose-response curves  were established in both series and it was found that without enflurane the ED50 of AH 8165 D was 8.29 mg/m2 and with enflurane 4.07 mg/m2. Therefore enflurane potentiates the action of AH 8165 D by 2.03 times, although it is impossible from this study to indicate precisely how and where enflurane can affect neuromuscular transmission."}
{"id": "PMID:21506", "title": "Duration of action of analgesic supplements to anesthesia. A double-blind comparison between morphine, fentanyl and sulfentanil.", "content": "In a double-blind trial, in a total of 45 patients,  sulfentanil was compared with fentanyl and morphine in equipotent doses, as a narcotic supplement to anesthesia. Initially, morphine was shown to have a significantly longer duration of effect than fentanyl and sulfentanil, which for the first 3 doses had similar durations of action to each other. Later doses of fentanyl, however, had an extended effect, presumably because of cumulation. This was not seen with sulfentanil.", "contents": "Duration of action of analgesic supplements to anesthesia. A double-blind comparison between morphine, fentanyl and sulfentanil. In a double-blind trial, in a total of 45 patients,  sulfentanil was compared with fentanyl and morphine in equipotent doses, as a narcotic supplement to anesthesia. Initially, morphine was shown to have a significantly longer duration of effect than fentanyl and sulfentanil, which for the first 3 doses had similar durations of action to each other. Later doses of fentanyl, however, had an extended effect, presumably because of cumulation. This was not seen with sulfentanil."}
{"id": "PMID:21507", "title": "Possible pathogenesis of Huntington's chorea and a new approach to treatment.", "content": "Recent identification of glutamate as a transmitter in neocortical efferents and discovery of toxic effects of excessive amounts of extra-cellular glutamate or its analogues on some brain neurons offer an explanation of the pathogenesis of Huntington's chorea. Cell death as well as consequent biochemical changes and clinical symptoms in this disease possibly result from excessive excitation of the neostriatal, and of some other neurons by glutamate released from neocortical axon terminals. If so, the development of Huntington's chorea could be prevented or arrested by blockers of glutamate transmissions, and folate should be reduced to the minimum in the diet of the genetically marked families.", "contents": "Possible pathogenesis of Huntington's chorea and a new approach to treatment. Recent identification of glutamate as a transmitter in neocortical efferents and discovery of toxic effects of excessive amounts of extra-cellular glutamate or its analogues on some brain neurons offer an explanation of the pathogenesis of Huntington's chorea. Cell death as well as consequent biochemical changes and clinical symptoms in this disease possibly result from excessive excitation of the neostriatal, and of some other neurons by glutamate released from neocortical axon terminals. If so, the development of Huntington's chorea could be prevented or arrested by blockers of glutamate transmissions, and folate should be reduced to the minimum in the diet of the genetically marked families."}
{"id": "PMID:21508", "title": "Acid production from Lycasin, maltitol, sorbitol and xylitol by oral streptococci and lactobacilli.", "content": "The acid production from maltitol was compared with the acid production from hydrogenated starch hydrolysate (Lycasin), sorbitol and xylitol by a number of oral strains and reference strains of Streptococcus mutans, S. sanguis, S. salivarius, S. mitior, S. milleri, S. faecalis, S. faecium, S. avium, Lactobacillus casei and L. salivarius. The polyols were added to a final concentration of 1.0% to two different basal media. Incubation was performed at 37 degrees C for 7 days after which the pH was recorded. Maltitol was fermented only by the lactobacilli (about two thirds of the strains). Lycasin was fermented by all strains of S. faecalis, more than 90% of the lactobacilli, about half of the S. sanguis strains, about one third of the S. mutans strains, and by a few other streptococcal strains. Acid production from sorbitol was observed among more than 80% of the S. mutans strains and the S. faecalis strains and most of the lactobacilli strains. Sorbitol-fermenting strains of S. sanguis and of S. mitior, all isolated from sorbitol-consumers, were observed. No other sorbitol-fermenting streptococci were found. Only the reference strains L. salivarius subsp. salivarius ATCC 11741 and S. avium ATCC 14025 fermented xylitol.", "contents": "Acid production from Lycasin, maltitol, sorbitol and xylitol by oral streptococci and lactobacilli. The acid production from maltitol was compared with the acid production from hydrogenated starch hydrolysate (Lycasin), sorbitol and xylitol by a number of oral strains and reference strains of Streptococcus mutans, S. sanguis, S. salivarius, S. mitior, S. milleri, S. faecalis, S. faecium, S. avium, Lactobacillus casei and L. salivarius. The polyols were added to a final concentration of 1.0% to two different basal media. Incubation was performed at 37 degrees C for 7 days after which the pH was recorded. Maltitol was fermented only by the lactobacilli (about two thirds of the strains). Lycasin was fermented by all strains of S. faecalis, more than 90% of the lactobacilli, about half of the S. sanguis strains, about one third of the S. mutans strains, and by a few other streptococcal strains. Acid production from sorbitol was observed among more than 80% of the S. mutans strains and the S. faecalis strains and most of the lactobacilli strains. Sorbitol-fermenting strains of S. sanguis and of S. mitior, all isolated from sorbitol-consumers, were observed. No other sorbitol-fermenting streptococci were found. Only the reference strains L. salivarius subsp. salivarius ATCC 11741 and S. avium ATCC 14025 fermented xylitol."}
{"id": "PMID:21511", "title": "[Cogan's syndrome].", "content": "Since Cogan described his first case in 1945, about 50 cases have been published in the world literature, A 23 year old patient who suffered from this disease led us to make a detailed study of previous publications. The cochleo-vestibular, the etiological and the ophtalmical aspects of the case were studied, and, also the differential diagnosis and the therapeutical possibilities.", "contents": "[Cogan's syndrome]. Since Cogan described his first case in 1945, about 50 cases have been published in the world literature, A 23 year old patient who suffered from this disease led us to make a detailed study of previous publications. The cochleo-vestibular, the etiological and the ophtalmical aspects of the case were studied, and, also the differential diagnosis and the therapeutical possibilities."}
{"id": "PMID:21512", "title": "Relapsing polychondritis. A clinical, pathologic-anatomic and histochemical study of 2 cases.", "content": "A 57-year-old man and a 70-year-old woman with relapsing polychondritis are reported. The man, suffering from arthralgias, respiratory obstruction, external ear and sanddle-nose deformities, conjunctivitis and irido-cyclitis, died after 4 years from airway obstruction because of tracheal and bronchial collapse. The woman is alive 8 months after the development of respiratory obstruction, probably caused by radiographically demonstrated tracheal obstruction, a saddle-nose deformity and hearing impairment. Microscopically, the involved cartilages showed degenerative and slight inflammatory changes and were eventually replaced by fibrous tissue. Histochemical studies, utilizing staining with Alcian blue at controlled electrolyte concentrations (Scott technique) and at controlled pH:s, with or without digestion with bacterial chondroitinase ABC; and staining with the PAS-method, with or without diastase digestion, revealed a complete or relative loss of glucosaminoglycans and glycogen. A biosynthetic defect is considered unlikely to be the primary pathogenetic mechanism of relapsing polychondritis. Histological and histochemical examination of biopsies from involved cartilages contribute to a definite diagnosis.", "contents": "Relapsing polychondritis. A clinical, pathologic-anatomic and histochemical study of 2 cases. A 57-year-old man and a 70-year-old woman with relapsing polychondritis are reported. The man, suffering from arthralgias, respiratory obstruction, external ear and sanddle-nose deformities, conjunctivitis and irido-cyclitis, died after 4 years from airway obstruction because of tracheal and bronchial collapse. The woman is alive 8 months after the development of respiratory obstruction, probably caused by radiographically demonstrated tracheal obstruction, a saddle-nose deformity and hearing impairment. Microscopically, the involved cartilages showed degenerative and slight inflammatory changes and were eventually replaced by fibrous tissue. Histochemical studies, utilizing staining with Alcian blue at controlled electrolyte concentrations (Scott technique) and at controlled pH:s, with or without digestion with bacterial chondroitinase ABC; and staining with the PAS-method, with or without diastase digestion, revealed a complete or relative loss of glucosaminoglycans and glycogen. A biosynthetic defect is considered unlikely to be the primary pathogenetic mechanism of relapsing polychondritis. Histological and histochemical examination of biopsies from involved cartilages contribute to a definite diagnosis."}
{"id": "PMID:21509", "title": "A dental splint for use during peroral endoscopy.", "content": "Damage to teeth is a well known complication of peroral endoscopy. A case is described in which potentially fatal complications of such damage occurred. This spurred on the development of a dental splint as an aid in the prevention of such damage. This splint is described, and evidence for the beneficial results of its use is presented.", "contents": "A dental splint for use during peroral endoscopy. Damage to teeth is a well known complication of peroral endoscopy. A case is described in which potentially fatal complications of such damage occurred. This spurred on the development of a dental splint as an aid in the prevention of such damage. This splint is described, and evidence for the beneficial results of its use is presented."}
{"id": "PMID:21513", "title": "Differetial staining of glycosaminoglycans, utilizing bacterial chondroitinase and chondrosulphatase.", "content": "A histochemical method for the differentiation of glucosaminoglycans, utilizing bacterial chondroitinase ABC and chondro-4- and -6 sulphatases, and staining with Alcian blue, is presented. The method is applied on human tissues with known glucosaminoglycan content (ganglion cyst, umbilical cord, foetal cartilage, adult cartilage) and the results are compared with the results obtained by staining with Alcian blue at controlled pH levels, with or without prior digestion with bovine testicular hyaloronidase, and the Scott method, utilizing  Alcian blue at varying concentrations of MgCl2. It is concluded that chondroitinase ABC digest chondroitin-4 and -6 sulphate and to some extent also hyaluronic acid and dermatan sulphate, but not heparin and keratosulphate.", "contents": "Differetial staining of glycosaminoglycans, utilizing bacterial chondroitinase and chondrosulphatase. A histochemical method for the differentiation of glucosaminoglycans, utilizing bacterial chondroitinase ABC and chondro-4- and -6 sulphatases, and staining with Alcian blue, is presented. The method is applied on human tissues with known glucosaminoglycan content (ganglion cyst, umbilical cord, foetal cartilage, adult cartilage) and the results are compared with the results obtained by staining with Alcian blue at controlled pH levels, with or without prior digestion with bovine testicular hyaloronidase, and the Scott method, utilizing  Alcian blue at varying concentrations of MgCl2. It is concluded that chondroitinase ABC digest chondroitin-4 and -6 sulphate and to some extent also hyaluronic acid and dermatan sulphate, but not heparin and keratosulphate."}
{"id": "PMID:21517", "title": "Cerebral blood flow and oxygen consumption in rat, measured with microspheres or xenon.", "content": "The cerebral blood flow and, in some rats, the cerebral rate of oxygen consumption were measured in three groups of male rats. Fractionation of radioisotope-labeled microspheres was used to measure regional cerebral blood flow in four parts of the rat brain. The arterial and cerebral venous concentrations of radioactive xenon during desaturation were used to measure the blood flow and oxygen consumption of cortex when venous blood was collected from the superior sagittal sinus, or of whole brain when the transverse sinus was sampled. The regional cerebral flow measured with microspheres had a large standard error reflecting the technical difficulty of this method. The cerebral blood flow measured with xenon was higher when venous blood was sampled from the superior sagittal sinus than when sampled from the transverse sinus, but cerebral oxygen consumption rates were similar. The difference reflects the greater trauma involved in the superior sagittal approach and possible extracerebral contamination present in the transverse sinus approach.", "contents": "Cerebral blood flow and oxygen consumption in rat, measured with microspheres or xenon. The cerebral blood flow and, in some rats, the cerebral rate of oxygen consumption were measured in three groups of male rats. Fractionation of radioisotope-labeled microspheres was used to measure regional cerebral blood flow in four parts of the rat brain. The arterial and cerebral venous concentrations of radioactive xenon during desaturation were used to measure the blood flow and oxygen consumption of cortex when venous blood was collected from the superior sagittal sinus, or of whole brain when the transverse sinus was sampled. The regional cerebral flow measured with microspheres had a large standard error reflecting the technical difficulty of this method. The cerebral blood flow measured with xenon was higher when venous blood was sampled from the superior sagittal sinus than when sampled from the transverse sinus, but cerebral oxygen consumption rates were similar. The difference reflects the greater trauma involved in the superior sagittal approach and possible extracerebral contamination present in the transverse sinus approach."}
{"id": "PMID:21518", "title": "Serum inorganic phosphate in middle-aged men. I. Inverse relation to body weight.", "content": "Serum inorganic phosphate was determined in 752 men born in 1926. An inverse correlation was found between serum inorganic phosphate levels and body weight. Other parameters of possible relevance to this finding, such as serum calcium, serum albumin, serum lambda-glutamyltransferase, and the occurrence of upper gastrointestinal disorders were analysed, and no correlations to the phosphate level were detected.", "contents": "Serum inorganic phosphate in middle-aged men. I. Inverse relation to body weight. Serum inorganic phosphate was determined in 752 men born in 1926. An inverse correlation was found between serum inorganic phosphate levels and body weight. Other parameters of possible relevance to this finding, such as serum calcium, serum albumin, serum lambda-glutamyltransferase, and the occurrence of upper gastrointestinal disorders were analysed, and no correlations to the phosphate level were detected."}
{"id": "PMID:21534", "title": "Introduction of artificial crosslinks into proteins.", "content": "In this chapter, we present a brief overview of the current status of protein crosslinking technology. An attempt is made to compare the natural crosslinks and natural crosslinking agents to the artificial ones, and a brief section is devoted to the potential use of enzymes (transglutaminase and peroxidase) as crosslinking agents in vitro. Homobifunctional (x-R-x) and heterobifunctional (x-R-y) reagents are considered in terms of the kinds of functional groups and R-groups that have been used in protein crosslinking, and some examples of reagents and applications from the recent literature are tabulated.", "contents": "Introduction of artificial crosslinks into proteins. In this chapter, we present a brief overview of the current status of protein crosslinking technology. An attempt is made to compare the natural crosslinks and natural crosslinking agents to the artificial ones, and a brief section is devoted to the potential use of enzymes (transglutaminase and peroxidase) as crosslinking agents in vitro. Homobifunctional (x-R-x) and heterobifunctional (x-R-y) reagents are considered in terms of the kinds of functional groups and R-groups that have been used in protein crosslinking, and some examples of reagents and applications from the recent literature are tabulated."}
{"id": "PMID:21535", "title": "Comparison of hydrophobic and strongly hydrophilic cleavable crosslinking reagents in intermolecular bond formation in aggregates of proteins or protein-RNA.", "content": "Most of the bifunctional reagents in protein chemistry possess a strongly hydrophobic backbone, derived from aliphatic or aromatic hydrocarbons. Even bifunctionals of more than 30 A in length of this sort form intramolecular bridges preferentially. In recent years, the intermolecular crosslinking of physiological protein aggregates has gained in importance. As shown in the crosslinking of hemoglobin with two sets of hydrophobic and strongly hydrophilic reagents, derived from azo dyes and tartaric acid, respectively, in this case it is not primarily the length of the bifunctional, but the hydrophilic structure that will enhance intermolecular crosslinking. Artificial dimers of native structure may be obtained. For the crosslinking of RNA to protein, we have synthesized a new reagent, 3-(2-bromo-3-oxobutane-1-sulphonyl)-propionic acid p-nitrophenyl ester. In a two step reaction, it is attached  to adenine and cytosine moieties at pH 6 first, and to lysine side chains at pH 7,5. The reagent has been applied to the poly-A sequence of globin messenger RNA nucleoprotein.", "contents": "Comparison of hydrophobic and strongly hydrophilic cleavable crosslinking reagents in intermolecular bond formation in aggregates of proteins or protein-RNA. Most of the bifunctional reagents in protein chemistry possess a strongly hydrophobic backbone, derived from aliphatic or aromatic hydrocarbons. Even bifunctionals of more than 30 A in length of this sort form intramolecular bridges preferentially. In recent years, the intermolecular crosslinking of physiological protein aggregates has gained in importance. As shown in the crosslinking of hemoglobin with two sets of hydrophobic and strongly hydrophilic reagents, derived from azo dyes and tartaric acid, respectively, in this case it is not primarily the length of the bifunctional, but the hydrophilic structure that will enhance intermolecular crosslinking. Artificial dimers of native structure may be obtained. For the crosslinking of RNA to protein, we have synthesized a new reagent, 3-(2-bromo-3-oxobutane-1-sulphonyl)-propionic acid p-nitrophenyl ester. In a two step reaction, it is attached  to adenine and cytosine moieties at pH 6 first, and to lysine side chains at pH 7,5. The reagent has been applied to the poly-A sequence of globin messenger RNA nucleoprotein."}
{"id": "PMID:21536", "title": "Comparison of wool reactions with selected mono and bifunctional reagents.", "content": "The molecular structure of wool is discussed in relation to chemical reactivity and  the  role of disulfide crosslinks. Ideal characteristics of an effective medium (e.g. dimethylformamide) for modifying wool include the ability to penetrate and swell wool without interfering with reagents used. The extent of reaction of wool or reduced wool is compared for mono-and bifunctional activated vinyl compounds, isocyanates, acid chlorides, acid anhydrides, sulfonyl chlorides, and alkyl halides. The degree of crosslinking is assessed by solubility, supercontraction, and tensile tests. Optical and electron scanning microscopy can give evidence of external polymer deposition in contrast to internal chemical modification. Effects of crosslinking by bifunctional reagents are related to changes in mechanical, chemical, and biological (moth-resisting) properties of the modified wool.", "contents": "Comparison of wool reactions with selected mono and bifunctional reagents. The molecular structure of wool is discussed in relation to chemical reactivity and  the  role of disulfide crosslinks. Ideal characteristics of an effective medium (e.g. dimethylformamide) for modifying wool include the ability to penetrate and swell wool without interfering with reagents used. The extent of reaction of wool or reduced wool is compared for mono-and bifunctional activated vinyl compounds, isocyanates, acid chlorides, acid anhydrides, sulfonyl chlorides, and alkyl halides. The degree of crosslinking is assessed by solubility, supercontraction, and tensile tests. Optical and electron scanning microscopy can give evidence of external polymer deposition in contrast to internal chemical modification. Effects of crosslinking by bifunctional reagents are related to changes in mechanical, chemical, and biological (moth-resisting) properties of the modified wool."}
{"id": "PMID:21537", "title": "Kinetic studies of immobilized alpha-chymotrypsin in apolar solvents.", "content": "The mechanism of alpha-chymotrypsin action has been probed by extending studies of native chymotrypsin to immobilized chymotrypsin, where the organic content of the solution can be raised to much higher levels and thus one can explicitly look at the role of water. When one does this, one finds that water only appears in the deacylation reaction. The premise that one can go from native chymotrypsin (souble) to immobilized chymotrypsin (insoluble) has been tested by several criteria. It has been found in many instances that the two are identical: in absolute rate, in pKa. They are, however, not identical to one another in binding, due to differences in diffusion, which is to be expected. Thus, mechanistically immobilized and native chymotrypsin are identical to one another and the use of immobilized chymotrypsin can be used to specify the mechanism even more: it must proceed through two tetrahedral intermediates and two acyl-enzyme intermediates.", "contents": "Kinetic studies of immobilized alpha-chymotrypsin in apolar solvents. The mechanism of alpha-chymotrypsin action has been probed by extending studies of native chymotrypsin to immobilized chymotrypsin, where the organic content of the solution can be raised to much higher levels and thus one can explicitly look at the role of water. When one does this, one finds that water only appears in the deacylation reaction. The premise that one can go from native chymotrypsin (souble) to immobilized chymotrypsin (insoluble) has been tested by several criteria. It has been found in many instances that the two are identical: in absolute rate, in pKa. They are, however, not identical to one another in binding, due to differences in diffusion, which is to be expected. Thus, mechanistically immobilized and native chymotrypsin are identical to one another and the use of immobilized chymotrypsin can be used to specify the mechanism even more: it must proceed through two tetrahedral intermediates and two acyl-enzyme intermediates."}
{"id": "PMID:21538", "title": "Factors affecting cyanoborohydride reduction of aromatic Schiff's bases in proteins.", "content": "Reductive alkylation of bovine serum albumin (BSA) and wool by a aromatic aldehydes and sodium cyanoborohydride has been investigated. The aldehydes used were chosen to allow convenient quantitative measurement of binding by ultraviolet spectroscopy. Alkylation of BSA occurred primarily at two highly reactive sites. Variation of time, PH, reactant concentration, and addition of urea had little effect on the extent of alkylation of BSA. However, more extensive alkylation was achieved in buffered aqueous dimethyl sulfoxide. The unusual reactivity of two epsilon-amino groups on the BSA molecule is attributed to closely placed lysine residues in the primary sequence rather than to favorable placement of unrelated, distant reactive centers. Similarly, only a few of the potentially available epsilon-amino groups of wool were observed to react.", "contents": "Factors affecting cyanoborohydride reduction of aromatic Schiff's bases in proteins. Reductive alkylation of bovine serum albumin (BSA) and wool by a aromatic aldehydes and sodium cyanoborohydride has been investigated. The aldehydes used were chosen to allow convenient quantitative measurement of binding by ultraviolet spectroscopy. Alkylation of BSA occurred primarily at two highly reactive sites. Variation of time, PH, reactant concentration, and addition of urea had little effect on the extent of alkylation of BSA. However, more extensive alkylation was achieved in buffered aqueous dimethyl sulfoxide. The unusual reactivity of two epsilon-amino groups on the BSA molecule is attributed to closely placed lysine residues in the primary sequence rather than to favorable placement of unrelated, distant reactive centers. Similarly, only a few of the potentially available epsilon-amino groups of wool were observed to react."}
{"id": "PMID:21540", "title": "Electron microscopy of an oligomeric protein stabilized by polyfunctional cross-linking.", "content": "Oligomeric proteins can be intramolecularly cross-linked with polylysine in a reaction in which a water soluble carbodiimide mediates an amide linkage between the protein carboxyl groups and the epsilon-amino groups of polylysine. Studies carried out with a cytochrome p-450 indicate that a small number of molecules in a population which has been cross-linked in this way retain important features of their tertiary and quaternary structure when negatively stained and examined in the electron microscope. Use of the method in determining the subunit geometry of oligomeric proteins is discussed.", "contents": "Electron microscopy of an oligomeric protein stabilized by polyfunctional cross-linking. Oligomeric proteins can be intramolecularly cross-linked with polylysine in a reaction in which a water soluble carbodiimide mediates an amide linkage between the protein carboxyl groups and the epsilon-amino groups of polylysine. Studies carried out with a cytochrome p-450 indicate that a small number of molecules in a population which has been cross-linked in this way retain important features of their tertiary and quaternary structure when negatively stained and examined in the electron microscope. Use of the method in determining the subunit geometry of oligomeric proteins is discussed."}
{"id": "PMID:21546", "title": "Cell transfer studies with the DK/or inbred chicken lines.", "content": "The histoincompatibility in the DK-OR-1 (B13B13) and DK/OR-3 (B19B19) inbred White Leghorn chicken lines was assessed with the Simonsen's spleen assay, GVHR mortality counts and antibody production by transferred cells in embryonic in vivo hosts. The two lines appear to be sufficiently histocompatible for use in cell transfer experiments. The occurrence of antigen responsive cells (ARC) and precursor cells in bone marrow as assessed with the in vivo culture and baby chick immune enhancement assays. Bone marrow of unimmunized donors possessed very little anti-MRBC immune responsiveness. Bone marrow cells from MRBC-primed donors, however, showed low anti-MRBC activity in the in vivo culture which could be elevated with a second antigen stimulation. Chicks grafted as embryos with bone marrow from immunized donors responded to MRBC immunization in an enhanced manner as compared to the control untreated chicks which responded poorly if at all to the antigen. Immunization appears (a) to increase the pool of potential ARC in the bone marrow of the donor and (b) to augment the responsiveness of bone marrow cells transferred into embryonic hosts.", "contents": "Cell transfer studies with the DK/or inbred chicken lines. The histoincompatibility in the DK-OR-1 (B13B13) and DK/OR-3 (B19B19) inbred White Leghorn chicken lines was assessed with the Simonsen's spleen assay, GVHR mortality counts and antibody production by transferred cells in embryonic in vivo hosts. The two lines appear to be sufficiently histocompatible for use in cell transfer experiments. The occurrence of antigen responsive cells (ARC) and precursor cells in bone marrow as assessed with the in vivo culture and baby chick immune enhancement assays. Bone marrow of unimmunized donors possessed very little anti-MRBC immune responsiveness. Bone marrow cells from MRBC-primed donors, however, showed low anti-MRBC activity in the in vivo culture which could be elevated with a second antigen stimulation. Chicks grafted as embryos with bone marrow from immunized donors responded to MRBC immunization in an enhanced manner as compared to the control untreated chicks which responded poorly if at all to the antigen. Immunization appears (a) to increase the pool of potential ARC in the bone marrow of the donor and (b) to augment the responsiveness of bone marrow cells transferred into embryonic hosts."}
{"id": "PMID:21547", "title": "Role of the major histocompatibility complex in resistance to Marek's disease: restriction of the growth of JMV-MD tumor cells in genetically resistant birds.", "content": "B21 is associated with resistance to Marek's disease (MD). Forty populations of chickens from all over the world were examined for the presence of the B21 allele. B21 was found in twelve of these populations and it's presence was confirmed by GVH testing in all ten populations which were tested. The populations in which B21 was detected represent the extreme production types of the species and include the progenitor of the species, the Red Jungle Fowl. Our studies suggest that B21 may have strong survival value for the species. An allogeneic transplantable lymphoma of MD, the JMV tumor cell line, grows more slowly in MD resistant (B21/B21) chicks than in MD susceptible (B2/B2) chicks. This is the first direct evidence that genetic resistance to MD may involve an active (immunological?) restriction of tumor cell growth. JMV cells were further characterized as a transplant of B1 carrying lymphoblastoid cells, an allele which may be associated with susceptibility to MD.", "contents": "Role of the major histocompatibility complex in resistance to Marek's disease: restriction of the growth of JMV-MD tumor cells in genetically resistant birds. B21 is associated with resistance to Marek's disease (MD). Forty populations of chickens from all over the world were examined for the presence of the B21 allele. B21 was found in twelve of these populations and it's presence was confirmed by GVH testing in all ten populations which were tested. The populations in which B21 was detected represent the extreme production types of the species and include the progenitor of the species, the Red Jungle Fowl. Our studies suggest that B21 may have strong survival value for the species. An allogeneic transplantable lymphoma of MD, the JMV tumor cell line, grows more slowly in MD resistant (B21/B21) chicks than in MD susceptible (B2/B2) chicks. This is the first direct evidence that genetic resistance to MD may involve an active (immunological?) restriction of tumor cell growth. JMV cells were further characterized as a transplant of B1 carrying lymphoblastoid cells, an allele which may be associated with susceptibility to MD."}
{"id": "PMID:21552", "title": "[Development cooperation in the development of a basic medical service].", "content": "Team work in building up a basic medical service. - This article reports on a project of Swiss aid to the developing country of the Peruvian Andes, whose organization is completely integrated into the national Peruvian ministry of health. After having stated the social and medical problems the article explains, how a team of Swiss doctors tries to reach to remote parts of a developing country by means of a medicine adapted to the economical situation of the poor farmer population. This is achieved by training local health auxiliaries and teaching them preventive medicine. On the other hand the curative medicine has to take second place and is concentrated mainly on a large scale tuberculosis programme. Ideas, experiences, problems and first evaluations are set out and discussed.", "contents": "[Development cooperation in the development of a basic medical service]. Team work in building up a basic medical service. - This article reports on a project of Swiss aid to the developing country of the Peruvian Andes, whose organization is completely integrated into the national Peruvian ministry of health. After having stated the social and medical problems the article explains, how a team of Swiss doctors tries to reach to remote parts of a developing country by means of a medicine adapted to the economical situation of the poor farmer population. This is achieved by training local health auxiliaries and teaching them preventive medicine. On the other hand the curative medicine has to take second place and is concentrated mainly on a large scale tuberculosis programme. Ideas, experiences, problems and first evaluations are set out and discussed."}
{"id": "PMID:21553", "title": "[Rural health center in Bali].", "content": "The rural Health Centre of Mengwi, on the island of Bali, was built and equipped for US $ 15,000 by Project Concern, a non-sectarian, medical relief organization. It has been run so successfully by them since it opened in 1974, that not only has the Centre gained the trust of the local community into which it is now fully integrated, but it is also regarded by the Indonesian Government as a pilot project. Amongst the factors leading to this success, the author underlines the following points: a suitable location for the Centre, easily accessible by the villagers; a local staff recruited from the villages of Mengwi District, well trained and sympathetic to the population; constant retraining of the staff leading to better medical care; the availability of a doctor and nurse around the clock; an adequate supply of drugs. Evaluation of the operation is best done by the acceptance of special programmes such as the Under-Five Clinic, the Family Planning Scheme, Ante-Natal Clinic and vaccinations. The mere success of the general clinic would not mean that the Centre had been integrated into the community and become a factor in rural development. The success of these special clinics, as well as the out-reach programmes, demonstrates that through adequate delivery of medical care, the Health Centre of Mengwi can now fulfil its role of being an important factor in the development of a rural community in the tropics.", "contents": "[Rural health center in Bali]. The rural Health Centre of Mengwi, on the island of Bali, was built and equipped for US $ 15,000 by Project Concern, a non-sectarian, medical relief organization. It has been run so successfully by them since it opened in 1974, that not only has the Centre gained the trust of the local community into which it is now fully integrated, but it is also regarded by the Indonesian Government as a pilot project. Amongst the factors leading to this success, the author underlines the following points: a suitable location for the Centre, easily accessible by the villagers; a local staff recruited from the villages of Mengwi District, well trained and sympathetic to the population; constant retraining of the staff leading to better medical care; the availability of a doctor and nurse around the clock; an adequate supply of drugs. Evaluation of the operation is best done by the acceptance of special programmes such as the Under-Five Clinic, the Family Planning Scheme, Ante-Natal Clinic and vaccinations. The mere success of the general clinic would not mean that the Centre had been integrated into the community and become a factor in rural development. The success of these special clinics, as well as the out-reach programmes, demonstrates that through adequate delivery of medical care, the Health Centre of Mengwi can now fulfil its role of being an important factor in the development of a rural community in the tropics."}
{"id": "PMID:21554", "title": "Development aid through information. Trying a new concept in Columbia.", "content": "The origin, execution, and preliminary results of a development project in Cali (Colombia) are presented. This project, which involves a special concept, aims at breaking new ground in the field of development aid. The aim of the Vivamos Mejor foundation, established in Colombia, is to provide practical help for poor families. The foundation is carrying out two model projects at the moment, which provide urgently required help and which at the same time investigate the feasibility and effectiveness of the projects in a scientific manner. Under the first project, teams of native inhabitants provide information and instruct the population thoroughly on questions of nutrition, hygiene, and birth control. Under the second project, children who are suffering from disease and malnutrition are temporarily rehabilitated in cr\u00e8ches, while at the same time their mothers learn how to provide the child and its brothers and sisters with a more healthy home. On one hand the Swiss projects in Cali aim at helping families in the poor areas there, while on the other, they are being scientifically analyzed as model projects in the hope that they can provide examples for the large cities in other developing countries.", "contents": "Development aid through information. Trying a new concept in Columbia. The origin, execution, and preliminary results of a development project in Cali (Colombia) are presented. This project, which involves a special concept, aims at breaking new ground in the field of development aid. The aim of the Vivamos Mejor foundation, established in Colombia, is to provide practical help for poor families. The foundation is carrying out two model projects at the moment, which provide urgently required help and which at the same time investigate the feasibility and effectiveness of the projects in a scientific manner. Under the first project, teams of native inhabitants provide information and instruct the population thoroughly on questions of nutrition, hygiene, and birth control. Under the second project, children who are suffering from disease and malnutrition are temporarily rehabilitated in cr\u00e8ches, while at the same time their mothers learn how to provide the child and its brothers and sisters with a more healthy home. On one hand the Swiss projects in Cali aim at helping families in the poor areas there, while on the other, they are being scientifically analyzed as model projects in the hope that they can provide examples for the large cities in other developing countries."}
{"id": "PMID:21555", "title": "[Water resources and health problems in developing countries].", "content": "The rapidly increasing use of water for agricultural and hydroelectric development in developing countries is causing serious health problems. These can be divided into two categories; the diseases whose transmission depends on water; and the changes in the life style of the population. We review briefly the principal health problems and analyze the principles to be followed in solving them, and the reasons of the success or failure of health programs. Among the topics we consider, are the development versus health, the collaboration of health service personnel with the rest of the personnel participating in water development schemes, the necessity of ensuring a multidisciplinary approach to the solutions of these health problems, the necessity of integration of the public health component within the administrative and budgetary levels and the coordination of public health measures with the development of project from the planning phase through the completion and maintenance phases, the purely medical aspects of the health problems involved appearing as being of secondary importance. Common sense, and the use of simple, cheap methods adapted to the local conditions, and applied focaly, provide better solutions than the sophisticated, more general and expensive approaches. The time and budget accorded for surveys and research, usually excessive, should be limited. It is necessary to adhere to a disciplined use of water. Ambitions and utopian dreams and strategies of disease eradication should, in general, give way to more limited, but accessible objectives, whose attainment would lead to a decrease of the clinical and socioeconomic gravity of the health problems to a \"reasonable\" level.", "contents": "[Water resources and health problems in developing countries]. The rapidly increasing use of water for agricultural and hydroelectric development in developing countries is causing serious health problems. These can be divided into two categories; the diseases whose transmission depends on water; and the changes in the life style of the population. We review briefly the principal health problems and analyze the principles to be followed in solving them, and the reasons of the success or failure of health programs. Among the topics we consider, are the development versus health, the collaboration of health service personnel with the rest of the personnel participating in water development schemes, the necessity of ensuring a multidisciplinary approach to the solutions of these health problems, the necessity of integration of the public health component within the administrative and budgetary levels and the coordination of public health measures with the development of project from the planning phase through the completion and maintenance phases, the purely medical aspects of the health problems involved appearing as being of secondary importance. Common sense, and the use of simple, cheap methods adapted to the local conditions, and applied focaly, provide better solutions than the sophisticated, more general and expensive approaches. The time and budget accorded for surveys and research, usually excessive, should be limited. It is necessary to adhere to a disciplined use of water. Ambitions and utopian dreams and strategies of disease eradication should, in general, give way to more limited, but accessible objectives, whose attainment would lead to a decrease of the clinical and socioeconomic gravity of the health problems to a \"reasonable\" level."}
{"id": "PMID:21556", "title": "[Community health aide. Critical estimation of his task within the nutrition program].", "content": "Community Health Aides (CHA), locally recruited and trained, visit households and identify malnourished children by means of weighing them in monthly intervals, recording the results on \"Gomez\" weight-for-age charts. The CHA acts as the people's nearest adviser. In order to become a useful if not the most important member of the health team, some common mistakes and distorted views should be corrected early in her career. The weight-for-age chart is an invaluable tool to record the child's state of health. It is the trend in weight gain that is relevant and not an isolated weight point on the graph. Maternal, perinatal and neonatal histories should be taken as they help to classify the low weight child. 3/4 of the children in the Young Child Nutrition Programme (YCNP) are underweight but also underheight for age. The designation of malnutrition grade I/II/III is misleading. Either one speaks of \"undernutrition\" if one considers weight-for-age only or one takes other anthropometric measurements such as the height or length in order to classify Protein-Energy-Malnutrition. A physical examination and clinical records are essential in the evaluation of malnutrition - one should not rely on the graph only. By measuring the height of children, one may well be surprised to discover that many children in St. James are on the obese side. Obesity is another form of malnutrition prevalent in the wealthy societies of western industrialized countries. It is paradox that we should increase the number of obese people in a world which is threatened by shortage of food energies and proteins.", "contents": "[Community health aide. Critical estimation of his task within the nutrition program]. Community Health Aides (CHA), locally recruited and trained, visit households and identify malnourished children by means of weighing them in monthly intervals, recording the results on \"Gomez\" weight-for-age charts. The CHA acts as the people's nearest adviser. In order to become a useful if not the most important member of the health team, some common mistakes and distorted views should be corrected early in her career. The weight-for-age chart is an invaluable tool to record the child's state of health. It is the trend in weight gain that is relevant and not an isolated weight point on the graph. Maternal, perinatal and neonatal histories should be taken as they help to classify the low weight child. 3/4 of the children in the Young Child Nutrition Programme (YCNP) are underweight but also underheight for age. The designation of malnutrition grade I/II/III is misleading. Either one speaks of \"undernutrition\" if one considers weight-for-age only or one takes other anthropometric measurements such as the height or length in order to classify Protein-Energy-Malnutrition. A physical examination and clinical records are essential in the evaluation of malnutrition - one should not rely on the graph only. By measuring the height of children, one may well be surprised to discover that many children in St. James are on the obese side. Obesity is another form of malnutrition prevalent in the wealthy societies of western industrialized countries. It is paradox that we should increase the number of obese people in a world which is threatened by shortage of food energies and proteins."}
{"id": "PMID:21557", "title": "Smallpox eradication in Rajasthan, India.", "content": "In 1962, when the smallpox eradication programme was launched in India, there were 3909 reported cases in Rajasthan. Mass vaccination was introduced but had little impact on the incidence of the disease; in 1970, 4074 cases were reported and in 1971, the reported incidence (4821 cases) was the highest in India. Changes in the vaccination technique, the use of a new and potent vaccine and the introduction of a new strategy based on surveillance and containment of outbreaks, rather than mass vaccination, brought good results. By 1972, only 1970 cases were reported and endemic smallpox was eliminated from Rajasthan before the launching of the intensified all-India compaign in July, 1973. In 1974, epidemics were occurring in the neighbouring states of Uttar Pradesh and Madhya Pradesh as well as in Bihar and West Bengal. But in that year, there were only 10 new smallpox outbreaks in Rajasthan, all originating from imported cases. The organization and progress of the eradication campaign and the history of smallpox eradication in Rajasthan are described in this communication.", "contents": "Smallpox eradication in Rajasthan, India. In 1962, when the smallpox eradication programme was launched in India, there were 3909 reported cases in Rajasthan. Mass vaccination was introduced but had little impact on the incidence of the disease; in 1970, 4074 cases were reported and in 1971, the reported incidence (4821 cases) was the highest in India. Changes in the vaccination technique, the use of a new and potent vaccine and the introduction of a new strategy based on surveillance and containment of outbreaks, rather than mass vaccination, brought good results. By 1972, only 1970 cases were reported and endemic smallpox was eliminated from Rajasthan before the launching of the intensified all-India compaign in July, 1973. In 1974, epidemics were occurring in the neighbouring states of Uttar Pradesh and Madhya Pradesh as well as in Bihar and West Bengal. But in that year, there were only 10 new smallpox outbreaks in Rajasthan, all originating from imported cases. The organization and progress of the eradication campaign and the history of smallpox eradication in Rajasthan are described in this communication."}
{"id": "PMID:21558", "title": "Malaria in the Republic of the Philippines. A review.", "content": "Malaria in the Republic of the Philippines is caused principally by P. falciparum and P. vivax, with the former as predominant species. P. malariae is occasionally reported, while P. ovale is very rare and has been reported only in the island of Palawan. Malaria is widespread in distribution with prevalence varying from one area to the other. In 1970, the malaria morbidity rate was reported to be 77.6 per 100,000 while the mortality rate was 1.8 per 100,000. Case detection activities revealed that, in 1973, the slide parasite rate was 7.2%, the annual parasite index was 6.1% and the annual blood examination rate was 8.4%. The principal vector of malaria in the Philippines is An. minimus flavirostris which breeds in clear, fresh-water streams in foothills and mountain slopes. An. mangyanus and An. maculatus appear to play a secondary role. The vectorial capacity of the former appears to be confined only where conditions are primitive, while the latter is associated with malaria transmission in high altitudes. In the absence of fresh-water streams, the salt-water breeder mosquito, An. litoralis, assumes the vectorial role. The epidemiology of malaria in the Philippines is discussed. Emergence of strains of P. falciparum with diminished sensitivity to the commonly used antimalarial drugs is reported in Palawan and Rizal provinces. The development of malaria control activities in the Philippines are presented. As of 1972, Cagayan Valley, Palawan, Mindoro, Sulu and circumscribed areas in Mindanao are still considered hard-core malarious areas with on-going persistent transmission.", "contents": "Malaria in the Republic of the Philippines. A review. Malaria in the Republic of the Philippines is caused principally by P. falciparum and P. vivax, with the former as predominant species. P. malariae is occasionally reported, while P. ovale is very rare and has been reported only in the island of Palawan. Malaria is widespread in distribution with prevalence varying from one area to the other. In 1970, the malaria morbidity rate was reported to be 77.6 per 100,000 while the mortality rate was 1.8 per 100,000. Case detection activities revealed that, in 1973, the slide parasite rate was 7.2%, the annual parasite index was 6.1% and the annual blood examination rate was 8.4%. The principal vector of malaria in the Philippines is An. minimus flavirostris which breeds in clear, fresh-water streams in foothills and mountain slopes. An. mangyanus and An. maculatus appear to play a secondary role. The vectorial capacity of the former appears to be confined only where conditions are primitive, while the latter is associated with malaria transmission in high altitudes. In the absence of fresh-water streams, the salt-water breeder mosquito, An. litoralis, assumes the vectorial role. The epidemiology of malaria in the Philippines is discussed. Emergence of strains of P. falciparum with diminished sensitivity to the commonly used antimalarial drugs is reported in Palawan and Rizal provinces. The development of malaria control activities in the Philippines are presented. As of 1972, Cagayan Valley, Palawan, Mindoro, Sulu and circumscribed areas in Mindanao are still considered hard-core malarious areas with on-going persistent transmission."}
{"id": "PMID:21559", "title": "Microfilarial polyarthritis in a massive Loa loa infestation. A case report.", "content": "A Cameroonian affected with massive Loa loa infection developed febrile arthritis with involvement of both knees and the left ankle. Although the patient was first seen by us after one month of treatment with Indomethacin, at this time the joints were still inflamed and microfilariae of Loa loa were found in the synovial fluid. No other etiological mechanism was identified. Following the articular puncture and treatment with Ketoprofen, the arthritis subsisted within a week. This is the first case to be studied in which arthritis during loasis has been explicitly documented by the presence of intra-articular microfilariae.", "contents": "Microfilarial polyarthritis in a massive Loa loa infestation. A case report. A Cameroonian affected with massive Loa loa infection developed febrile arthritis with involvement of both knees and the left ankle. Although the patient was first seen by us after one month of treatment with Indomethacin, at this time the joints were still inflamed and microfilariae of Loa loa were found in the synovial fluid. No other etiological mechanism was identified. Following the articular puncture and treatment with Ketoprofen, the arthritis subsisted within a week. This is the first case to be studied in which arthritis during loasis has been explicitly documented by the presence of intra-articular microfilariae."}
{"id": "PMID:21561", "title": "Ambulatory management in alcoholism.", "content": "In the acute phase, management begins with ruling out conditions that would require hospitalization. Moderate withdrawal symptoms in susceptible patients require substitution medication which can be monitored on an outpatient basis. In the subacute phase, after withdrawal, frequent visits, family education and judicious use of drugs are required. Depressive reactions are common. There are no reliable indexes for predicting the success of a return to controlled drinking.", "contents": "Ambulatory management in alcoholism. In the acute phase, management begins with ruling out conditions that would require hospitalization. Moderate withdrawal symptoms in susceptible patients require substitution medication which can be monitored on an outpatient basis. In the subacute phase, after withdrawal, frequent visits, family education and judicious use of drugs are required. Depressive reactions are common. There are no reliable indexes for predicting the success of a return to controlled drinking."}
{"id": "PMID:21563", "title": "Lower-esophageal sphincter function does not determine resting upper-esophageal sphincter pressure.", "content": "Records of 269 esophageal motility studies were reviewed to determine the relationship between lower-esophageal sphincter (LES) function and upper-esophageal sphincter (UES) pressure. Average and greatest UES pressures were similar in patients with LES  pressures less than 10 mm Hg or greater than 20 mm Hg, and in patients with and without gastroesophageal reflux as determined by an intraesophageal pH electrode test. Although teliologically appealing, the belief that patients with weak lower-esophageal sphincters and gastroesophageal reflux have stronger upper-esophageal sphincters to guard against pharyngeal reflux and aspiration cannot be confirmed by current manometric techniques.", "contents": "Lower-esophageal sphincter function does not determine resting upper-esophageal sphincter pressure. Records of 269 esophageal motility studies were reviewed to determine the relationship between lower-esophageal sphincter (LES) function and upper-esophageal sphincter (UES) pressure. Average and greatest UES pressures were similar in patients with LES  pressures less than 10 mm Hg or greater than 20 mm Hg, and in patients with and without gastroesophageal reflux as determined by an intraesophageal pH electrode test. Although teliologically appealing, the belief that patients with weak lower-esophageal sphincters and gastroesophageal reflux have stronger upper-esophageal sphincters to guard against pharyngeal reflux and aspiration cannot be confirmed by current manometric techniques."}
{"id": "PMID:21564", "title": "Effect of multiple-stress procedures on monkey gastroduodenal mucosa, serum gastrin, and hydrogen ion kinetics.", "content": "By arranging a series of psychological contingencies (unpredictability, uncontrollability, conflict), coupled with delivery of a physical stimulus (electric shock), we produced gastroduodenal mucosal lesions in 7 of 8 rhesus monkeys. The most severe conflict paradigm most consistently produced lesions across subjects. Of the 30 lesions observed by endoscopy, 80% occurred near the anatomic junction of gastric body and antrum, in the antrum, or in the duodenum. Lesions varied in severity from discolorations of the mucosa to disruptions of mucosal integrity. Lesions in the stomach generally disappeared in several days despite the continuation of stress; some duodenal lesions were equally evanescent, but in 2 monkeys, lesions lasted over a week. Hydrogen ion kinetics were measured in 2 monkeys that developed gastric lesions and 2 that developed duodenal lesions. The rate at which hydrogen ion entered the duodenum was uniformly suppressed for all 4 monkeys during their first session of shock avoidance; during their last session, the gastric subgroup continued to show suppression while the duodenal subgroup returned towards control levels. Serum gastrin levels were unchanged by the multiple-stress procedures. Our finding of consistently producible, stress-induced gastroduodenal pathology in anatomic areas similar to those involved in man suggests that the subhuman primate is suitable for further efforts to produce an animal model of psychosomatic ulcer disease.", "contents": "Effect of multiple-stress procedures on monkey gastroduodenal mucosa, serum gastrin, and hydrogen ion kinetics. By arranging a series of psychological contingencies (unpredictability, uncontrollability, conflict), coupled with delivery of a physical stimulus (electric shock), we produced gastroduodenal mucosal lesions in 7 of 8 rhesus monkeys. The most severe conflict paradigm most consistently produced lesions across subjects. Of the 30 lesions observed by endoscopy, 80% occurred near the anatomic junction of gastric body and antrum, in the antrum, or in the duodenum. Lesions varied in severity from discolorations of the mucosa to disruptions of mucosal integrity. Lesions in the stomach generally disappeared in several days despite the continuation of stress; some duodenal lesions were equally evanescent, but in 2 monkeys, lesions lasted over a week. Hydrogen ion kinetics were measured in 2 monkeys that developed gastric lesions and 2 that developed duodenal lesions. The rate at which hydrogen ion entered the duodenum was uniformly suppressed for all 4 monkeys during their first session of shock avoidance; during their last session, the gastric subgroup continued to show suppression while the duodenal subgroup returned towards control levels. Serum gastrin levels were unchanged by the multiple-stress procedures. Our finding of consistently producible, stress-induced gastroduodenal pathology in anatomic areas similar to those involved in man suggests that the subhuman primate is suitable for further efforts to produce an animal model of psychosomatic ulcer disease."}
{"id": "PMID:21565", "title": "The natural history of neoplasia. Newer insights into an old problem.", "content": "The stages of initiation and promotion in the natural history of epidermal carcinogenesis have been known for many years. Recently, experimental systems other than skin have been shown to exhibit similar, if not completely analogous, stages in the natural history of neoplasia. In particular, the demonstration by Peraino and his associates that phenobarbital may enhance the production of hepatomas by a relatively subcarcinogenic dose of acetylaminofluorene was one of the first demonstrations of stages occurring in an extraepidermal neoplasm. Studies reported in this paper have demonstrated that administration of phenobarbital (0.05% in the diet) for 6 months following a single dose of diethylnitrosamine (5 to 10 mg/kg) given within 24 hours after partial hepatectomy resulted in a marked increase in the number of enzyme-altered foci in the liver as well as in the production of hepatocellular carcinomas. This was compared to animals receiving only a single dose of diethylnitrosamine following partial hepatectomy with no further treatment, in which only a relatively small number of foci were evident in the absence of phenobarbital feeding. Using three different enzyme markers, a distinct degree of phenotypic heterogeneity of the enzyme-altered foci in liver was demonstrated. These studies have shown that liver carcinogensis can be readily divided into two stages: a) initiation by a single dose of diethylnitrosamine following partial hepatectomy and b) promotion by the continuous feeding of phenobarbital. Furthermore, the immediate progeny of the initiated cells, the enzyme-altered focus, may be recognized by suitable microscopic means prior to the formation of gross lesions as required in the skin system. These initiated cell populations exhibit a degree of biochemical heterogeneity which reflects that seen in fully developed hepatic neoplasms, suggesting that promotion and progression in this system does not significantly alter the basic biochemical characteristics of the initiated cell.", "contents": "The natural history of neoplasia. Newer insights into an old problem. The stages of initiation and promotion in the natural history of epidermal carcinogenesis have been known for many years. Recently, experimental systems other than skin have been shown to exhibit similar, if not completely analogous, stages in the natural history of neoplasia. In particular, the demonstration by Peraino and his associates that phenobarbital may enhance the production of hepatomas by a relatively subcarcinogenic dose of acetylaminofluorene was one of the first demonstrations of stages occurring in an extraepidermal neoplasm. Studies reported in this paper have demonstrated that administration of phenobarbital (0.05% in the diet) for 6 months following a single dose of diethylnitrosamine (5 to 10 mg/kg) given within 24 hours after partial hepatectomy resulted in a marked increase in the number of enzyme-altered foci in the liver as well as in the production of hepatocellular carcinomas. This was compared to animals receiving only a single dose of diethylnitrosamine following partial hepatectomy with no further treatment, in which only a relatively small number of foci were evident in the absence of phenobarbital feeding. Using three different enzyme markers, a distinct degree of phenotypic heterogeneity of the enzyme-altered foci in liver was demonstrated. These studies have shown that liver carcinogensis can be readily divided into two stages: a) initiation by a single dose of diethylnitrosamine following partial hepatectomy and b) promotion by the continuous feeding of phenobarbital. Furthermore, the immediate progeny of the initiated cells, the enzyme-altered focus, may be recognized by suitable microscopic means prior to the formation of gross lesions as required in the skin system. These initiated cell populations exhibit a degree of biochemical heterogeneity which reflects that seen in fully developed hepatic neoplasms, suggesting that promotion and progression in this system does not significantly alter the basic biochemical characteristics of the initiated cell."}
{"id": "PMID:21566", "title": "Kinetic differences between uterine and renal renins in the dog.", "content": "It has previously been reported that in the dog the Michaelis constant (Km) of renal renin with respect to homologous plasma substrate is the same as that for the angiotensin-generating enzyme extractable from the myometrium during pregnancy. We have reexamined the kinetics with a different methodology. Enzyme preparations from dog kidneys, the uterus of a nonnephrectomized pregnant bitch, and the uterus of a nephrectomized pregnant bitch were used. The substrate, prepared by diluting plasma from a nephrectomized, hysterectomized pregnant bitch, had a maximum endogenous substrate concentration of 1,750 ng/ml angiotensin I equivalents. Lineweaver-Burk kinetic analysis was used to calculate the Michaelis constants at pH 6.2. The Km of the renal enzyme was 720 ng/ml, of the enzyme prepared from the nonnephrectomized uterus 1,570 ng/ml, and of the nephrectomized dog uterus 1,500 ng/ml. The uterine enzyme was not activated by transient acid treatment, in contrast to renins reported from other sources. The data support the concept of biochemical heterogeneity of the two enzymes in the dog.", "contents": "Kinetic differences between uterine and renal renins in the dog. It has previously been reported that in the dog the Michaelis constant (Km) of renal renin with respect to homologous plasma substrate is the same as that for the angiotensin-generating enzyme extractable from the myometrium during pregnancy. We have reexamined the kinetics with a different methodology. Enzyme preparations from dog kidneys, the uterus of a nonnephrectomized pregnant bitch, and the uterus of a nephrectomized pregnant bitch were used. The substrate, prepared by diluting plasma from a nephrectomized, hysterectomized pregnant bitch, had a maximum endogenous substrate concentration of 1,750 ng/ml angiotensin I equivalents. Lineweaver-Burk kinetic analysis was used to calculate the Michaelis constants at pH 6.2. The Km of the renal enzyme was 720 ng/ml, of the enzyme prepared from the nonnephrectomized uterus 1,570 ng/ml, and of the nephrectomized dog uterus 1,500 ng/ml. The uterine enzyme was not activated by transient acid treatment, in contrast to renins reported from other sources. The data support the concept of biochemical heterogeneity of the two enzymes in the dog."}
{"id": "PMID:21567", "title": "pH-temperature dependence of organic acid transport in rat kidney slices.", "content": "Uptake of p-aminohippurate (PAH) by rat kidney slices was optimal at a pH of around 7.3 when incubation temperature was 37 degrees C. At 25 degrees C, however, optimal pH was increased to about 7.5. When the uptake was evaluated as a function of the OH/H ratio of the medium, it was found that optimal uptake is at a constant OH/H. Data showing the same characteristics of OH/H dependence were also observed for phenol red. Passive uptake of PAH was pH independent. Efflux rates for PAH also showed the pH optimal which was identical to that of uptake. At both 25 and 37 degrees C the Km appeared to be independent of pH while the maximum rate of active influx. An optimal OH/H ratio determines maximal velocity and this ratio is fixed and independent of temperature.", "contents": "pH-temperature dependence of organic acid transport in rat kidney slices. Uptake of p-aminohippurate (PAH) by rat kidney slices was optimal at a pH of around 7.3 when incubation temperature was 37 degrees C. At 25 degrees C, however, optimal pH was increased to about 7.5. When the uptake was evaluated as a function of the OH/H ratio of the medium, it was found that optimal uptake is at a constant OH/H. Data showing the same characteristics of OH/H dependence were also observed for phenol red. Passive uptake of PAH was pH independent. Efflux rates for PAH also showed the pH optimal which was identical to that of uptake. At both 25 and 37 degrees C the Km appeared to be independent of pH while the maximum rate of active influx. An optimal OH/H ratio determines maximal velocity and this ratio is fixed and independent of temperature."}
{"id": "PMID:21568", "title": "Ionic composition of arterial and mixed venous plasma in the unanesthetized dog.", "content": "The use of permanent catheters in the aorta and pulmonary artery permitted the establishment of normal values for hemoglobin concentration in blood and -or pH, PCO2, osmolality, and protein and electrolyte concentrations in the plasma of arterial and venous samples from unanesthetized, undisturbed dogs, and the comparison of the ionic composition of simultaneously taken arterial and venous samples. Arterial samples yielded the following mean values: CHb, 143 g liter-1; pHP, 7.427; PCO2, 32.5 mmHg; CPosmol, 295 mmol kg-1; CPpr, 73.1 g liter-1, CPNa+, 148.0; CPK+, 3.9; CPCa2+, 2.38; CPMg2+, 0.85; CPCl-, 116.0; CPHCO3-, 21.1; CPlact-, 1.4; CPphosph, 1.21; net cation equivalency, 16.4; and anion gap, 1.03 mmol liter-1 in eight male mongrel dogs with seven or eight samplings from each dog. The anion gap in arterial and venous plasma was small, indicating that the contribution of sulfate and organic acids to the ionic composition of dog plasma is quantitatively unimportant. In simultaneously taken arterial and venous samples the following significant arteriovenous differences were found: HP, +0.038; PCO2, -5.6 mmHg; CPosmol, -1.8 mmol kg-1; protein, -0.8 g liter-1; CPNa+, -1.0; CPK+, -0.1; CPCl-, +1.3; and CPHCO3-, -1.7 mmol liter-1. These differences are explained on the basis of the changes that occur in blood upon the addition of CO2 and the ensuing chloride and water shifts.", "contents": "Ionic composition of arterial and mixed venous plasma in the unanesthetized dog. The use of permanent catheters in the aorta and pulmonary artery permitted the establishment of normal values for hemoglobin concentration in blood and -or pH, PCO2, osmolality, and protein and electrolyte concentrations in the plasma of arterial and venous samples from unanesthetized, undisturbed dogs, and the comparison of the ionic composition of simultaneously taken arterial and venous samples. Arterial samples yielded the following mean values: CHb, 143 g liter-1; pHP, 7.427; PCO2, 32.5 mmHg; CPosmol, 295 mmol kg-1; CPpr, 73.1 g liter-1, CPNa+, 148.0; CPK+, 3.9; CPCa2+, 2.38; CPMg2+, 0.85; CPCl-, 116.0; CPHCO3-, 21.1; CPlact-, 1.4; CPphosph, 1.21; net cation equivalency, 16.4; and anion gap, 1.03 mmol liter-1 in eight male mongrel dogs with seven or eight samplings from each dog. The anion gap in arterial and venous plasma was small, indicating that the contribution of sulfate and organic acids to the ionic composition of dog plasma is quantitatively unimportant. In simultaneously taken arterial and venous samples the following significant arteriovenous differences were found: HP, +0.038; PCO2, -5.6 mmHg; CPosmol, -1.8 mmol kg-1; protein, -0.8 g liter-1; CPNa+, -1.0; CPK+, -0.1; CPCl-, +1.3; and CPHCO3-, -1.7 mmol liter-1. These differences are explained on the basis of the changes that occur in blood upon the addition of CO2 and the ensuing chloride and water shifts."}
{"id": "PMID:21569", "title": "Mechanism of active chloride transport by urinary bladder of the Colombian toad.", "content": "In order to investigate the mechanism of active chloride transport, experiments were performed to verify the previous report that removal of potassium from the solutions bathing the urinary bladders of Colombian toads induced a reversal of short-circuit current (RSCC) and active chloride transport. The present experiments confirmed these findings. However, there was no correlation between the magnitude of the RSCC and the chloride transport. Furthermore, removal of chloride from the mucosal bathing solutions did not markedly affect the RSCC, indicating that the chloride transport was electrically silent. Removal of bicarbonate from the bathing solutions eliminated the RSCC, and acetazolamide inhibited both the RSCC and net chloride transport. These findings suggest a relationship between chloride and hydrogen ion transport. Inhibition of sodium transport by removal of sodium or addition of ouabain or amiloride has previously been shown to produce an RSCC. In the present experiments these same maneuvers caused an RSCC and induced net chloride transport. It is concluded that active chloride transport by Colombian toad bladder is stimulated by inhibition of sodium transport. The inhibition of active chloride transport by acetazolamide suggests a possible role for carbonic anhydrase in this process.", "contents": "Mechanism of active chloride transport by urinary bladder of the Colombian toad. In order to investigate the mechanism of active chloride transport, experiments were performed to verify the previous report that removal of potassium from the solutions bathing the urinary bladders of Colombian toads induced a reversal of short-circuit current (RSCC) and active chloride transport. The present experiments confirmed these findings. However, there was no correlation between the magnitude of the RSCC and the chloride transport. Furthermore, removal of chloride from the mucosal bathing solutions did not markedly affect the RSCC, indicating that the chloride transport was electrically silent. Removal of bicarbonate from the bathing solutions eliminated the RSCC, and acetazolamide inhibited both the RSCC and net chloride transport. These findings suggest a relationship between chloride and hydrogen ion transport. Inhibition of sodium transport by removal of sodium or addition of ouabain or amiloride has previously been shown to produce an RSCC. In the present experiments these same maneuvers caused an RSCC and induced net chloride transport. It is concluded that active chloride transport by Colombian toad bladder is stimulated by inhibition of sodium transport. The inhibition of active chloride transport by acetazolamide suggests a possible role for carbonic anhydrase in this process."}
{"id": "PMID:21570", "title": "The brain as a dream state generator: an activation-synthesis hypothesis of the dream process.", "content": "Recent research in the neurobiology of dreaming sleep provides new evidence for possible structural and functional substrates of formal aspects of the dream process. The data suggest that dreaming sleep is physiologically determined and shaped by a brain stem neuronal mechanism that can be modeled physiologically and mathematically. Formal features of the generator processes with strong implications for dream theory include periodicity and automaticity of forebrain activation, suggesting a preprogrammed neural basis for dream mentation in sleep; intense and sporadic activation of brain stem sensorimotor circuits including reticular, oculomotor, and vestibular neurons, possibly determining spatiotemporal aspects of dream imagery; and shifts in transmitter ratios, possibly accounting for dream amnesia. The authors suggest that the automatically activated forebrain synthesizes the dream by comparing information generated in specific brain stem circuits with information stored in memory.", "contents": "The brain as a dream state generator: an activation-synthesis hypothesis of the dream process. Recent research in the neurobiology of dreaming sleep provides new evidence for possible structural and functional substrates of formal aspects of the dream process. The data suggest that dreaming sleep is physiologically determined and shaped by a brain stem neuronal mechanism that can be modeled physiologically and mathematically. Formal features of the generator processes with strong implications for dream theory include periodicity and automaticity of forebrain activation, suggesting a preprogrammed neural basis for dream mentation in sleep; intense and sporadic activation of brain stem sensorimotor circuits including reticular, oculomotor, and vestibular neurons, possibly determining spatiotemporal aspects of dream imagery; and shifts in transmitter ratios, possibly accounting for dream amnesia. The authors suggest that the automatically activated forebrain synthesizes the dream by comparing information generated in specific brain stem circuits with information stored in memory."}
{"id": "PMID:21571", "title": "An evaluation of a unique new antipsychotic agent, sulpiride: effects on serum prolactin and growth hormone levels.", "content": "Sulpiride is a new and chemically different neuroleptic. In a study of 16 severely ill schizophrenic patients, this compound displayed definite evidence of antipsychotic activity while producing few adverse reactions. The relative absence of extrapyramidal side effects may indicate that sulpride has a low potential for producing tardive dyskinesia. Two patients who did not develop significant increases in prolactin levels did show a definite therapeutic response to sulpiride. Thus it appears that central dopaminergic blockade in the hypothalamic area is not a prerequisite for antipsychotic activity.", "contents": "An evaluation of a unique new antipsychotic agent, sulpiride: effects on serum prolactin and growth hormone levels. Sulpiride is a new and chemically different neuroleptic. In a study of 16 severely ill schizophrenic patients, this compound displayed definite evidence of antipsychotic activity while producing few adverse reactions. The relative absence of extrapyramidal side effects may indicate that sulpride has a low potential for producing tardive dyskinesia. Two patients who did not develop significant increases in prolactin levels did show a definite therapeutic response to sulpiride. Thus it appears that central dopaminergic blockade in the hypothalamic area is not a prerequisite for antipsychotic activity."}
{"id": "PMID:21572", "title": "[Long-term study on the influence of running exercise, food restriction, running exercise + food restriction and of parenterally applicated testis cells on age-parameters of the rat (author's transl)].", "content": "Preliminary results of a long-term study on 1100 male Sprague-Dawley rats are presented, showing the influence of running exercise, of restricted diet, of both of these together and of the s.c. application of lypholized testis cells. Up to now animals aged 9, 15 and 24 mths were investigated. The test-animals were exposed to the experimental conditions from their 6th month of life. The running exercise was carried out on a treadmill (30 m at a speed of 25 m/min, horizontal) 5 days a week. A food restriction of about 20% was achieved by 2 fasting-days a week. The lyophilized testis cells were injected for the first time at an age of 9 mths and afterwards in 6 mths intervals. Between the injection and the assessment of the age-parameters there was an interval of 6 mths. S o fare the following parameters of the comprehensive test-program have been evaluated: 1) running performance in m (treadmill, 20 m/min, ascent 15 degrees), 2) motor activity (Animex Activity Meter), 3) chemical contraction-relaxation of tail-tendon-fibers, 4) total lipids and total cholesterol in the plasma. The results obtained so far show that a mild regular training, moderate food restriction and the s.c. application of testis-cells are able to cause a significant shift in the dirction of a younger biological age in at least some of the age parameters. The action of the testis-cells seems to affect most of the age parameters but shows the tendency to be more distinct at a higher age. More concrete statements about the influence on the biological age or the vitality will only be possible after the multivariate analysis of the results.", "contents": "[Long-term study on the influence of running exercise, food restriction, running exercise + food restriction and of parenterally applicated testis cells on age-parameters of the rat (author's transl)]. Preliminary results of a long-term study on 1100 male Sprague-Dawley rats are presented, showing the influence of running exercise, of restricted diet, of both of these together and of the s.c. application of lypholized testis cells. Up to now animals aged 9, 15 and 24 mths were investigated. The test-animals were exposed to the experimental conditions from their 6th month of life. The running exercise was carried out on a treadmill (30 m at a speed of 25 m/min, horizontal) 5 days a week. A food restriction of about 20% was achieved by 2 fasting-days a week. The lyophilized testis cells were injected for the first time at an age of 9 mths and afterwards in 6 mths intervals. Between the injection and the assessment of the age-parameters there was an interval of 6 mths. S o fare the following parameters of the comprehensive test-program have been evaluated: 1) running performance in m (treadmill, 20 m/min, ascent 15 degrees), 2) motor activity (Animex Activity Meter), 3) chemical contraction-relaxation of tail-tendon-fibers, 4) total lipids and total cholesterol in the plasma. The results obtained so far show that a mild regular training, moderate food restriction and the s.c. application of testis-cells are able to cause a significant shift in the dirction of a younger biological age in at least some of the age parameters. The action of the testis-cells seems to affect most of the age parameters but shows the tendency to be more distinct at a higher age. More concrete statements about the influence on the biological age or the vitality will only be possible after the multivariate analysis of the results."}
{"id": "PMID:21573", "title": "Effect of aminoglutethimide on calcitonin sensitivity.", "content": "Studying the influence of aminoglutethimide treatment on calcitonin sensitivity, serum calcium levels were measured in normal rats, aminoglutethimide treated rats, adrenalectomized and castrated rats, following i.v. injection of porcine calcitonin. The aminoglutethimide administration caused a more distinct calcitonin resistance than surgical sex hormone deprivation. It was found that castration in most of experiments failed to enhance calcitonin resistance in aminoglutethimide treated animals. The aminoglutethimide administration may influence the steroid synthesis of adrenals, accessory adrenals and testes too. Results obtained with castrated, aminoglutethimide plus dehydroepiandrosterone treated and castrated, aminoglutethimide plus epiandrosterone treated rats affirm the earlier observations, i.e. in state of sex hormone deficiency the exogeneous androgens have an enhancing or restoring effect on calcitonin sensitivity.", "contents": "Effect of aminoglutethimide on calcitonin sensitivity. Studying the influence of aminoglutethimide treatment on calcitonin sensitivity, serum calcium levels were measured in normal rats, aminoglutethimide treated rats, adrenalectomized and castrated rats, following i.v. injection of porcine calcitonin. The aminoglutethimide administration caused a more distinct calcitonin resistance than surgical sex hormone deprivation. It was found that castration in most of experiments failed to enhance calcitonin resistance in aminoglutethimide treated animals. The aminoglutethimide administration may influence the steroid synthesis of adrenals, accessory adrenals and testes too. Results obtained with castrated, aminoglutethimide plus dehydroepiandrosterone treated and castrated, aminoglutethimide plus epiandrosterone treated rats affirm the earlier observations, i.e. in state of sex hormone deficiency the exogeneous androgens have an enhancing or restoring effect on calcitonin sensitivity."}
{"id": "PMID:21574", "title": "[General directions for the care of the dying patient by the Swiss Academy of Medical Sciences (author's transl)].", "content": "The medical ethical and legal principles for the care of the dying are given, different for the patient with judgement and for the inconscieous patient. Contrary to the patient in danger of death (Moriturus) where the doctor has the duty to save the live, in the case of the dying (Moribundus), where the disease is irreversible and the prognosis irremediable, passive euthanasy is permitted. Here the human assistance from man to man is essential. In a separate paper of the directions answer is given to special medical questions in the care of the dying.", "contents": "[General directions for the care of the dying patient by the Swiss Academy of Medical Sciences (author's transl)]. The medical ethical and legal principles for the care of the dying are given, different for the patient with judgement and for the inconscieous patient. Contrary to the patient in danger of death (Moriturus) where the doctor has the duty to save the live, in the case of the dying (Moribundus), where the disease is irreversible and the prognosis irremediable, passive euthanasy is permitted. Here the human assistance from man to man is essential. In a separate paper of the directions answer is given to special medical questions in the care of the dying."}
{"id": "PMID:21575", "title": "[Somatical performance and environment in the elderly (author's transl)].", "content": "The arrangement with the envirement requires somatical performance of men. We developed a mathematical model by recording data of performance. This model shows a decreasing capacity of performance correlated with age. The real meassured data are vastly different to theoretical conception. In difference to the assumption equal increasing load in elder and younger people leads to equal acceleration of pulse rate we are able to demonstrate decreasing physical strength is clutched to shortage of weight. The loss of performance in elderly men requires a restriction either of social contacts or of supply and consumption. For preserve of physical strength there is required to treat malnutrition and especially to promote vigour, substance an strength of muscles.", "contents": "[Somatical performance and environment in the elderly (author's transl)]. The arrangement with the envirement requires somatical performance of men. We developed a mathematical model by recording data of performance. This model shows a decreasing capacity of performance correlated with age. The real meassured data are vastly different to theoretical conception. In difference to the assumption equal increasing load in elder and younger people leads to equal acceleration of pulse rate we are able to demonstrate decreasing physical strength is clutched to shortage of weight. The loss of performance in elderly men requires a restriction either of social contacts or of supply and consumption. For preserve of physical strength there is required to treat malnutrition and especially to promote vigour, substance an strength of muscles."}
{"id": "PMID:21576", "title": "Thermal contraction-relaxation and dissolution of rat tail tendon collagen in different ages.", "content": "Here thermal contraction-relaxation and dissolution of collagen from rat tail tendon fibers were studied simultaneously. It is concluded that both processes change their character in the same manner with increasing age and that the relaxation phase probably is a result of the dissolution of collagen from the fibers.", "contents": "Thermal contraction-relaxation and dissolution of rat tail tendon collagen in different ages. Here thermal contraction-relaxation and dissolution of collagen from rat tail tendon fibers were studied simultaneously. It is concluded that both processes change their character in the same manner with increasing age and that the relaxation phase probably is a result of the dissolution of collagen from the fibers."}
{"id": "PMID:21577", "title": "[Acute confusional states in the elderly (author's transl)].", "content": "It is described that the acute confusional state in elderly people can be regarded as the combination of a catastrophe-reaction, superimposed on the primary symptoms of an underlying physical disorder. The catastrophe-reaction, the secondary symptoms, are described as the manifestation of the failure of the hypothalamo-hypophyso-adrenocortical axis, comparable with a relative glucocorticosteroid deficiency. The therapy of an acute confusional state should aim at the treatment of the underlying physical disorder and at the treatment of the catastrophereaction by injecting intramuscularly for two days high doses of methyl-prednisolon. It is demonstrated that frequently in elderly people a subacute confusion can be developed, due to a catastrophe-reaction, superimposed on an underlying masked depression. A combined treatment, giving for two days high doses of methyl-prednisolon in order to treat the catastrophe-reaction and giving low doses of tricyclic anti-depressants to treat the depression, seems to result in amazing improvement.", "contents": "[Acute confusional states in the elderly (author's transl)]. It is described that the acute confusional state in elderly people can be regarded as the combination of a catastrophe-reaction, superimposed on the primary symptoms of an underlying physical disorder. The catastrophe-reaction, the secondary symptoms, are described as the manifestation of the failure of the hypothalamo-hypophyso-adrenocortical axis, comparable with a relative glucocorticosteroid deficiency. The therapy of an acute confusional state should aim at the treatment of the underlying physical disorder and at the treatment of the catastrophereaction by injecting intramuscularly for two days high doses of methyl-prednisolon. It is demonstrated that frequently in elderly people a subacute confusion can be developed, due to a catastrophe-reaction, superimposed on an underlying masked depression. A combined treatment, giving for two days high doses of methyl-prednisolon in order to treat the catastrophe-reaction and giving low doses of tricyclic anti-depressants to treat the depression, seems to result in amazing improvement."}
{"id": "PMID:21596", "title": "Estimation of plasma lorazepam by gas-liquid chromatography and a benzene extraction.", "content": "Plasma lorazepam can be easily and reliably estimated using a simple single stage benzene extraction and gas-lizuid chromatography with flunitrazepam as the internal standard. Reproducible results within the clinical range of plasma levels were obtained. This method permits the extraction and chromatographing of 40 samples in approximately 7 1/2 hours.", "contents": "Estimation of plasma lorazepam by gas-liquid chromatography and a benzene extraction. Plasma lorazepam can be easily and reliably estimated using a simple single stage benzene extraction and gas-lizuid chromatography with flunitrazepam as the internal standard. Reproducible results within the clinical range of plasma levels were obtained. This method permits the extraction and chromatographing of 40 samples in approximately 7 1/2 hours."}
{"id": "PMID:21603", "title": "Determinants of lung bacterial clearance in mice after acute hypoxia.", "content": "Net lung bacterial clearance in normal mice is determined by the balance of in vivo bacterial multiplication on the one hand, and the defense mechanisms of mucociliary clearance and phagocytosis and killing by the oxygen-dependent alveolar macrophage on the other. The bactericidal function of the macrophage is the major component of the defense mechanism. The effect of acute hypoxia on the defense mechanism was studied in mice exposed to aerosols of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. Physical clearance was not impaired by acute hypoxia, and bacterial replication was not stimulated by the low oxygen atmosphere. Clearance of Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli was impaired during acute hypoxia due to decreased phagocytosis or killing by the alveolar macrophage. The important human pathogen Streptococcus pneumoniae was cleared normally in the presence of acute hypoxia. This observation suggests that an oxygen-independent clearance mechanism is important in lung defense against the pneumococcus. This may be a separate mechanism within the alveolar macrophage or a system as yet unidentified.", "contents": "Determinants of lung bacterial clearance in mice after acute hypoxia. Net lung bacterial clearance in normal mice is determined by the balance of in vivo bacterial multiplication on the one hand, and the defense mechanisms of mucociliary clearance and phagocytosis and killing by the oxygen-dependent alveolar macrophage on the other. The bactericidal function of the macrophage is the major component of the defense mechanism. The effect of acute hypoxia on the defense mechanism was studied in mice exposed to aerosols of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. Physical clearance was not impaired by acute hypoxia, and bacterial replication was not stimulated by the low oxygen atmosphere. Clearance of Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli was impaired during acute hypoxia due to decreased phagocytosis or killing by the alveolar macrophage. The important human pathogen Streptococcus pneumoniae was cleared normally in the presence of acute hypoxia. This observation suggests that an oxygen-independent clearance mechanism is important in lung defense against the pneumococcus. This may be a separate mechanism within the alveolar macrophage or a system as yet unidentified."}
{"id": "PMID:21604", "title": "Detection of penumococcal antigens in the sputum in pneumococcal pneumonia.", "content": "Forty-seven patients with bacterial pneumonia were grouped by use of clinical criteria according to the relative certainty of a diagnosis of pneumococcal pneumonia. Sputums were tested for pneumococcal antigens by counterimmunoelectrophoresis with polyvalent pneumococcal antiserum. Antigens were detected in the sputum of 29 of 39 patients with evidence of pneumococcal pneumonia, and there was good correlation between the detection of antigens and the degree of certainty of the clinical diagnosis. Antigens persisted briefly in the sputum during therapy with antimicrobial drugs and could be detected during the first 48 hours of therapy in most cases of pneumococcal pneumonia. Pneumococci were isolated from the sputum in only 18 of 39 cases of pneumococcal pneumonia, and sputum cultures did not correlate as well as counterimmunoelectrophoresis with clinical diagnoses. In studies of 27 patients with chronic bronchitis without pneumonia, pneumococci were isolated from sputum in 10 cases, whereas counterimmunoelectrophoresis was positive in 5 cases. Counterimmunoelectrophoresis provides a simple and rapid method for detecting pneumococcal antigens in sputum, and it appears to be more reliable than sputum cultures in establishing a presumptive diagnosis in pneumococcal pneumonia.", "contents": "Detection of penumococcal antigens in the sputum in pneumococcal pneumonia. Forty-seven patients with bacterial pneumonia were grouped by use of clinical criteria according to the relative certainty of a diagnosis of pneumococcal pneumonia. Sputums were tested for pneumococcal antigens by counterimmunoelectrophoresis with polyvalent pneumococcal antiserum. Antigens were detected in the sputum of 29 of 39 patients with evidence of pneumococcal pneumonia, and there was good correlation between the detection of antigens and the degree of certainty of the clinical diagnosis. Antigens persisted briefly in the sputum during therapy with antimicrobial drugs and could be detected during the first 48 hours of therapy in most cases of pneumococcal pneumonia. Pneumococci were isolated from the sputum in only 18 of 39 cases of pneumococcal pneumonia, and sputum cultures did not correlate as well as counterimmunoelectrophoresis with clinical diagnoses. In studies of 27 patients with chronic bronchitis without pneumonia, pneumococci were isolated from sputum in 10 cases, whereas counterimmunoelectrophoresis was positive in 5 cases. Counterimmunoelectrophoresis provides a simple and rapid method for detecting pneumococcal antigens in sputum, and it appears to be more reliable than sputum cultures in establishing a presumptive diagnosis in pneumococcal pneumonia."}
{"id": "PMID:21606", "title": "Regional quality control survey of blood-gas analysis.", "content": "We undertook an external quality control survey of blood-gas analysis in 16 laboratories at 13 hospitals. All samples were prepared in the laboratories under investigation by equilibration of blood or serum with gas mixtures of known composition. pH of serum was measured with no significant bias but with an SD of random error 0.026 pH units, which was almost twice the SD of the reference range (0.015). An acceptable random error (half SD of reference range) was not obtained in a longitudinal internal quality control suvey although there were acceptable results for buffer pH in both field and internal surveys. Blood PO2 was measured with no significant bias but with SD of random error 1.38 kPa which reduced to 0.72 kPa by excluding one egregious result. The latter value was just over half of the SD of the reference range (1.2 kPa). PCO2 of blood was also measured without significant bias but with a much smaller SD of random error of 0.28 kPa (by excluding one egregious result), which was again just over half the SD of the reference range (0.51 kPa). Measurements of blood PO2 and PCO2 seem generally acceptable in relation to their respective reference ranges but measurements of pH were unsatisfactory in both internal and external trials.", "contents": "Regional quality control survey of blood-gas analysis. We undertook an external quality control survey of blood-gas analysis in 16 laboratories at 13 hospitals. All samples were prepared in the laboratories under investigation by equilibration of blood or serum with gas mixtures of known composition. pH of serum was measured with no significant bias but with an SD of random error 0.026 pH units, which was almost twice the SD of the reference range (0.015). An acceptable random error (half SD of reference range) was not obtained in a longitudinal internal quality control suvey although there were acceptable results for buffer pH in both field and internal surveys. Blood PO2 was measured with no significant bias but with SD of random error 1.38 kPa which reduced to 0.72 kPa by excluding one egregious result. The latter value was just over half of the SD of the reference range (1.2 kPa). PCO2 of blood was also measured without significant bias but with a much smaller SD of random error of 0.28 kPa (by excluding one egregious result), which was again just over half the SD of the reference range (0.51 kPa). Measurements of blood PO2 and PCO2 seem generally acceptable in relation to their respective reference ranges but measurements of pH were unsatisfactory in both internal and external trials."}
{"id": "PMID:21607", "title": "A long-term evaluation of the CentrifiChem centrifugal microanalyser during routine use in the clinical biochemistry laboratory.", "content": "The CentrifiChem centrifugal microanalyser (model 300) has been used routinely in this laboratory for two years. Its reliability for performing total bilirubin, aspartate aminotransferase alkaline phosphatase and gamma-glutamyl transferase analyses during this time is reported, using methods modified in a preliminary study. Accuracy of the analyses has been assessed by comparing the results with those from other analytical systems and by using commercial control sera. Determinations have been made for within-batch, between-day (20 days), and long term (100 weeks) precision. Other aspects evaluated were the range over which methods were linear and the cost of operation.", "contents": "A long-term evaluation of the CentrifiChem centrifugal microanalyser during routine use in the clinical biochemistry laboratory. The CentrifiChem centrifugal microanalyser (model 300) has been used routinely in this laboratory for two years. Its reliability for performing total bilirubin, aspartate aminotransferase alkaline phosphatase and gamma-glutamyl transferase analyses during this time is reported, using methods modified in a preliminary study. Accuracy of the analyses has been assessed by comparing the results with those from other analytical systems and by using commercial control sera. Determinations have been made for within-batch, between-day (20 days), and long term (100 weeks) precision. Other aspects evaluated were the range over which methods were linear and the cost of operation."}
{"id": "PMID:21608", "title": "The genetic and biochemical properties of the D-amino acid oxidases in human tissues.", "content": "1. Two distinct forms of oxidases catalysing the oxidative deamidation of D-alpha-amino acids have been identified in human tissues: D-amino acid oxidase (DAMOX) and D-aspartate oxidase (DASOX). 2. The enzymes differ in their electrophoretic properties, tissue distribution, binding with flavine adenine denucleotide, heat stability, molecular size and possibly in subunit structure. 3. Neither enzyme exhibits genetic polymorphism in European populations, but a rare electrophoretic variant phenotype (DASOX 2-1) was identified which suggests that the DASOX locus is autosomal and independent of the DAMOX locus.", "contents": "The genetic and biochemical properties of the D-amino acid oxidases in human tissues. 1. Two distinct forms of oxidases catalysing the oxidative deamidation of D-alpha-amino acids have been identified in human tissues: D-amino acid oxidase (DAMOX) and D-aspartate oxidase (DASOX). 2. The enzymes differ in their electrophoretic properties, tissue distribution, binding with flavine adenine denucleotide, heat stability, molecular size and possibly in subunit structure. 3. Neither enzyme exhibits genetic polymorphism in European populations, but a rare electrophoretic variant phenotype (DASOX 2-1) was identified which suggests that the DASOX locus is autosomal and independent of the DAMOX locus."}
{"id": "PMID:21605", "title": "[Anhidrotic activity of anticholinergics in mice. Influence of mode of administration].", "content": "Anhidrotic concentrations 50 of four anticholinergics were determined in mice using an original skin palmar conductance method. Intra-peritoneal, intra-palmar and topical routes were compared. Relative anhidrotic activities according to the mode of administration of the different anticholinergics showed definite differences, e.g. hydroxyzine, which was the less active per i.p. route, was the most active per topical route. The method is likely to be a useful test for selecting the most active anticholinergic and its most efficient route of administration for the treatment of hyperhidrosis.", "contents": "[Anhidrotic activity of anticholinergics in mice. Influence of mode of administration]. Anhidrotic concentrations 50 of four anticholinergics were determined in mice using an original skin palmar conductance method. Intra-peritoneal, intra-palmar and topical routes were compared. Relative anhidrotic activities according to the mode of administration of the different anticholinergics showed definite differences, e.g. hydroxyzine, which was the less active per i.p. route, was the most active per topical route. The method is likely to be a useful test for selecting the most active anticholinergic and its most efficient route of administration for the treatment of hyperhidrosis."}
{"id": "PMID:21610", "title": "Hepatotoxicity of erythromycin estolate during pregnancy.", "content": "Women in the second half of pregnancy, who were infected with genital mycoplasmas and who gave written informed consent, were randomly assigned to receive capsules of identical appearance containing erythromycin estolate, clindamycin hydrochloride, or a placebo for 6 weeks. Levels of serum glutamic oxalacetic transaminase (SGOT) were determined before and during treatment by a fluorometric method. All pretreatment levels of SGOT were normal (<41 units). Participants who received erythromycin estolate had significantly more abnormally elevated levels of SGOT (16/161, 9.9%) than did those who received clindamycin (4/168, 2.4%, P < 0.01) or those who received placebo (3/165, 1.8%, P < 0.01). Elevated levels of SGOT ranged from 44 to 130 U. Serum bilirubin levels were normal. Gamma-glutamyl transpeptidase activity was abnormal in six of six participants who had abnormal levels of SGOT while receiving erythromycin estolate. There were few associated symptoms, and all levels of SGOT returned to normal after cessation of treatment. The treatment of pregnant women with erythromycin estolate may be inadvisable.", "contents": "Hepatotoxicity of erythromycin estolate during pregnancy. Women in the second half of pregnancy, who were infected with genital mycoplasmas and who gave written informed consent, were randomly assigned to receive capsules of identical appearance containing erythromycin estolate, clindamycin hydrochloride, or a placebo for 6 weeks. Levels of serum glutamic oxalacetic transaminase (SGOT) were determined before and during treatment by a fluorometric method. All pretreatment levels of SGOT were normal (<41 units). Participants who received erythromycin estolate had significantly more abnormally elevated levels of SGOT (16/161, 9.9%) than did those who received clindamycin (4/168, 2.4%, P < 0.01) or those who received placebo (3/165, 1.8%, P < 0.01). Elevated levels of SGOT ranged from 44 to 130 U. Serum bilirubin levels were normal. Gamma-glutamyl transpeptidase activity was abnormal in six of six participants who had abnormal levels of SGOT while receiving erythromycin estolate. There were few associated symptoms, and all levels of SGOT returned to normal after cessation of treatment. The treatment of pregnant women with erythromycin estolate may be inadvisable."}
{"id": "PMID:21611", "title": "Mutation of an inosine-producing strain of Bacillus subtilis to DL-methionine sulfoxide resistance for guanosine production.", "content": "An inosine-producing strain of Bacillus subtilis was mutated to resistance against the antagonist of glutamine, DL-methionine sulfoxide. Among the mutants derived, guanosine producers were observed frequently. The best strain, 14119, produced 9.6 g of guanosine per liter at a weight yield of 12% from consumed sugar. Inosine production decreased concomitantly. When resistance was increased further by exposure to higher doses of DL-methionine sulfoxide, another strain, AG169, was obtained that did not excrete inosine but produced increased amounts of xanthosine. In these strains, the specific activity of 5'-nucleotidase was lower and that of inosine 5'-monophosphate (IMP) dehydrogenase was higher than the parent strain. It is speculated that the metabolic flow from IMP to xanthosine 5'-monophosphate proceeds more smoothly than that from IMP  to inosine and yields more xanthosine and guanosine.", "contents": "Mutation of an inosine-producing strain of Bacillus subtilis to DL-methionine sulfoxide resistance for guanosine production. An inosine-producing strain of Bacillus subtilis was mutated to resistance against the antagonist of glutamine, DL-methionine sulfoxide. Among the mutants derived, guanosine producers were observed frequently. The best strain, 14119, produced 9.6 g of guanosine per liter at a weight yield of 12% from consumed sugar. Inosine production decreased concomitantly. When resistance was increased further by exposure to higher doses of DL-methionine sulfoxide, another strain, AG169, was obtained that did not excrete inosine but produced increased amounts of xanthosine. In these strains, the specific activity of 5'-nucleotidase was lower and that of inosine 5'-monophosphate (IMP) dehydrogenase was higher than the parent strain. It is speculated that the metabolic flow from IMP to xanthosine 5'-monophosphate proceeds more smoothly than that from IMP  to inosine and yields more xanthosine and guanosine."}
{"id": "PMID:21612", "title": "Production, purification, and characterization of alpha-amylase from Thermomonospora curvata.", "content": "Thermomonospora curvata produces an extracellular alpha-amylase. Maximal amylase production by cultures in a starch-mineral salts medium occurred at pH 7.5 and 53 degrees C. The crude enzyme was unstable to heating (65 degrees C) at pH 4 to 6, and was activated when heated at pH 8. The enzyme was purified 66-fold with a 9% yield and appeared homogeneous on discontinuous gel electrophoresis. The pH and temperature optima for activity of the purified enzyme were 5.5 to 6.0 and 65 degrees C. The molecular weight was calculated to be 62,000. The Km for starch was 0.39 mg/ml. The amylolytic pattern consisted of a mixture of maltotetraose and maltopentaose.", "contents": "Production, purification, and characterization of alpha-amylase from Thermomonospora curvata. Thermomonospora curvata produces an extracellular alpha-amylase. Maximal amylase production by cultures in a starch-mineral salts medium occurred at pH 7.5 and 53 degrees C. The crude enzyme was unstable to heating (65 degrees C) at pH 4 to 6, and was activated when heated at pH 8. The enzyme was purified 66-fold with a 9% yield and appeared homogeneous on discontinuous gel electrophoresis. The pH and temperature optima for activity of the purified enzyme were 5.5 to 6.0 and 65 degrees C. The molecular weight was calculated to be 62,000. The Km for starch was 0.39 mg/ml. The amylolytic pattern consisted of a mixture of maltotetraose and maltopentaose."}
{"id": "PMID:21613", "title": "Bacterial lipopolysaccharides as inducers of disease resistance in tobacco.", "content": "The cell wall component of Pseudomonas solanacearum that induces disease resistance in tobacco was highly heat stable at neutral or alkaline pH but highly labile at acid pH. Activity was unaffected by nucleases and proteases but destroyed by a mixture of beta-glycosidases. Washing of bacterial cell walls released a lipopolysaccharide (LPS) fraction with high inducer activity. Purified LPS, extracted by a variety of procedures from whole cells, isolated cell walls, and culture filtrates of both smooth and rough forms of P. solanacearum, induced disease resistance in tobacco at concentrations as low as 50 microgram/ml. The LPS from the non-plant pathogens Escherichia coli B, E. coli K, and Serratia marcescens was also active. Cell wall protein, free phospholipid, and nucleic acids were not necessary for activity. Moreover, since LPS from rough forms was active, the O-specific polysaccharide of the LPS was not required for activity. Hydrolysis of the remaining core-lipid A linkage or deacylation of lipid A destroyed inducer activity. When injected into tobacco leaves, purified LPS attached to tobacco mesophyll cell walls and induced ultrastructural changes in the host cell similar to those induced by attachment of whole heat-killed bacteria.", "contents": "Bacterial lipopolysaccharides as inducers of disease resistance in tobacco. The cell wall component of Pseudomonas solanacearum that induces disease resistance in tobacco was highly heat stable at neutral or alkaline pH but highly labile at acid pH. Activity was unaffected by nucleases and proteases but destroyed by a mixture of beta-glycosidases. Washing of bacterial cell walls released a lipopolysaccharide (LPS) fraction with high inducer activity. Purified LPS, extracted by a variety of procedures from whole cells, isolated cell walls, and culture filtrates of both smooth and rough forms of P. solanacearum, induced disease resistance in tobacco at concentrations as low as 50 microgram/ml. The LPS from the non-plant pathogens Escherichia coli B, E. coli K, and Serratia marcescens was also active. Cell wall protein, free phospholipid, and nucleic acids were not necessary for activity. Moreover, since LPS from rough forms was active, the O-specific polysaccharide of the LPS was not required for activity. Hydrolysis of the remaining core-lipid A linkage or deacylation of lipid A destroyed inducer activity. When injected into tobacco leaves, purified LPS attached to tobacco mesophyll cell walls and induced ultrastructural changes in the host cell similar to those induced by attachment of whole heat-killed bacteria."}
{"id": "PMID:21634", "title": "Effect of blood transfusion in low birthweight infants.", "content": "143 fresh blood transfusions were given to 32 low birthweight babies, 28 of whom had hyaline membrane disease. The arterial or central venous pressure was raised by a blood transfusion if before transfusion the mean arterial pressure was less than 35 mmHg or if the diastolic central venous pressure was less than -- 0-5 mmHg. There was no effect of blood transfusion on pH. It therefore appears either that metabolic acidosis in hyaline membrane disease is not caused by poor peripheral perfusion or that blood transfusion does not increase peripheral blood flow in this condition. The safety of the procedure is assessed.", "contents": "Effect of blood transfusion in low birthweight infants. 143 fresh blood transfusions were given to 32 low birthweight babies, 28 of whom had hyaline membrane disease. The arterial or central venous pressure was raised by a blood transfusion if before transfusion the mean arterial pressure was less than 35 mmHg or if the diastolic central venous pressure was less than -- 0-5 mmHg. There was no effect of blood transfusion on pH. It therefore appears either that metabolic acidosis in hyaline membrane disease is not caused by poor peripheral perfusion or that blood transfusion does not increase peripheral blood flow in this condition. The safety of the procedure is assessed."}
{"id": "PMID:21637", "title": "Effect of glucocorticoids on the hexose monophosphate pathway in human rheumatoid synovial lining cells in vitro and in vivo.", "content": "Human rheumatoid synovial lining cells have up to four times the capacity to oxidize glucose 6-phosphate, the first step of the hexose monophosphate pathway, as do the nonrheumatoid cells. The reducing equivalents produced by this system have many significant metabolic effects. Exposure of these cells by 10(-5) M prednisolone in vitro, or to 6 mg/day in vivo, causes some depression of this activity in the rheumatoid synovial lining cells; less than this dose of steroid, or the administration of nonsteroidal drugs in vivo, has little or no effect. The depression of activity produced by 6 mg/day does not bring this activity down to the value found in nonrheumatoid synoviocytes.", "contents": "Effect of glucocorticoids on the hexose monophosphate pathway in human rheumatoid synovial lining cells in vitro and in vivo. Human rheumatoid synovial lining cells have up to four times the capacity to oxidize glucose 6-phosphate, the first step of the hexose monophosphate pathway, as do the nonrheumatoid cells. The reducing equivalents produced by this system have many significant metabolic effects. Exposure of these cells by 10(-5) M prednisolone in vitro, or to 6 mg/day in vivo, causes some depression of this activity in the rheumatoid synovial lining cells; less than this dose of steroid, or the administration of nonsteroidal drugs in vivo, has little or no effect. The depression of activity produced by 6 mg/day does not bring this activity down to the value found in nonrheumatoid synoviocytes."}
{"id": "PMID:21638", "title": "Release of antral and duodenal gastrin in response to an intestinal meal.", "content": "In dogs prepared with isolated, innervated antral pouches, intraduodenal perfusion with liver extract at pH 7, with the atrum buffered at pH 7, resulted in a significant release of gastrin selectively from the antrum and from the duodenum. Acidification of the meal to pH 1 abolished both antral and duodenal gastrin release, whereas acidification of the antrum abolished only the antral gastrin response. After antrectomy, liver extract at pH 7 caused a diminished but significant release of duodenal gastrin. These studies provide evidence that an intestinal meal may release (in addition to a specific intestinal phase hormone) gastrin from the intestine, and from antrum, by means of a pH-sensitive mechanism which may involve a humoral agent (enterobombesin?) from the small bowel.", "contents": "Release of antral and duodenal gastrin in response to an intestinal meal. In dogs prepared with isolated, innervated antral pouches, intraduodenal perfusion with liver extract at pH 7, with the atrum buffered at pH 7, resulted in a significant release of gastrin selectively from the antrum and from the duodenum. Acidification of the meal to pH 1 abolished both antral and duodenal gastrin release, whereas acidification of the antrum abolished only the antral gastrin response. After antrectomy, liver extract at pH 7 caused a diminished but significant release of duodenal gastrin. These studies provide evidence that an intestinal meal may release (in addition to a specific intestinal phase hormone) gastrin from the intestine, and from antrum, by means of a pH-sensitive mechanism which may involve a humoral agent (enterobombesin?) from the small bowel."}
{"id": "PMID:21639", "title": "Hydroxylation of 5,5-diphenylhydantoin (phenytoin) by dog liver microsomes.", "content": "Chang and Glazko in 1972 had reported failure to demonstrate any production from 5-5-diphenylhydantoin (phenytoin, DPH) by dog liver microsomes of either 5-(m-hydroxyphenyl-5-phenylhydantoin (m-HPPH) or 5-(P-hydroxyphenyl-5-phenylhydantoin (p-HPPH), metabolites of DPH  produced by the dog in vivo. We have incubated DPH with 9,000 X g supermatants of dog liver homogenates and with suspensions of separated microsomes with added NADPH generating system, Mg(2+), and nicotinamide and have demonstrated the production of both m-HPPH and p-HPPH. Both metabolities were detected by thin-layer chromatography of extracts of the incubation mixtures. Detection and roughly quantitative measurement of m-HPPH were also accomplished with gas chromatography.", "contents": "Hydroxylation of 5,5-diphenylhydantoin (phenytoin) by dog liver microsomes. Chang and Glazko in 1972 had reported failure to demonstrate any production from 5-5-diphenylhydantoin (phenytoin, DPH) by dog liver microsomes of either 5-(m-hydroxyphenyl-5-phenylhydantoin (m-HPPH) or 5-(P-hydroxyphenyl-5-phenylhydantoin (p-HPPH), metabolites of DPH  produced by the dog in vivo. We have incubated DPH with 9,000 X g supermatants of dog liver homogenates and with suspensions of separated microsomes with added NADPH generating system, Mg(2+), and nicotinamide and have demonstrated the production of both m-HPPH and p-HPPH. Both metabolities were detected by thin-layer chromatography of extracts of the incubation mixtures. Detection and roughly quantitative measurement of m-HPPH were also accomplished with gas chromatography."}
{"id": "PMID:21641", "title": "[pH and lactic acid values in the cerebrospinal fluid as a diagnostic aid for differentiating viral and purulent meningoencephalitis].", "content": "Concentrations of lactate and pH were determined in the CSF of 20 normal children, 36 with viral meningitis, 16 with purulent meningitis and six with tuberculous meningitis. No differences were found between normal cases and those with viral meningitis. In patients with purulent meningitis concentration of lactate was above 30 mg/100 ml and pH below 7.3. Both determinations allowed differentiation between viral meningitis and purulent meningitis after 48 hr of treatment with antibiotics in 80% of the cases.", "contents": "[pH and lactic acid values in the cerebrospinal fluid as a diagnostic aid for differentiating viral and purulent meningoencephalitis]. Concentrations of lactate and pH were determined in the CSF of 20 normal children, 36 with viral meningitis, 16 with purulent meningitis and six with tuberculous meningitis. No differences were found between normal cases and those with viral meningitis. In patients with purulent meningitis concentration of lactate was above 30 mg/100 ml and pH below 7.3. Both determinations allowed differentiation between viral meningitis and purulent meningitis after 48 hr of treatment with antibiotics in 80% of the cases."}
{"id": "PMID:21642", "title": "[Acid-base status in the blood of domestic pigs during exhausting locomotor stress of small and medium intensity].", "content": "Twenty-two fattening pigs were stressed until their rectal temperatures had reached 42 degrees C. The means of stress included walking on moving conveyor belt at ambient temperatures between 22 degrees C and 27 degrees C and relative humidities between 69 and 98%, belt speeds of 0.7 m/s, 1.3 m/s or 0.7 m/s, and stimulation by means of a forcing rod. Rectal temperature, respiratory frequency, lactic acid level in blood plasma, pH, as well as pCO2 and base excess in the blood were measured prior to, during, and after stressing. Gasping was strongly pronounced due to severe alkalisis, but it was somewhat mitigated on running on the belt with exposure to additional stress on account of lactic acid accumulation in the plasma.", "contents": "[Acid-base status in the blood of domestic pigs during exhausting locomotor stress of small and medium intensity]. Twenty-two fattening pigs were stressed until their rectal temperatures had reached 42 degrees C. The means of stress included walking on moving conveyor belt at ambient temperatures between 22 degrees C and 27 degrees C and relative humidities between 69 and 98%, belt speeds of 0.7 m/s, 1.3 m/s or 0.7 m/s, and stimulation by means of a forcing rod. Rectal temperature, respiratory frequency, lactic acid level in blood plasma, pH, as well as pCO2 and base excess in the blood were measured prior to, during, and after stressing. Gasping was strongly pronounced due to severe alkalisis, but it was somewhat mitigated on running on the belt with exposure to additional stress on account of lactic acid accumulation in the plasma."}
{"id": "PMID:21644", "title": "Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with melperone or thiothixene.", "content": "Psychotic women with schizophrenic symptoms were treated with melperone 100 mg X 3 (n = 29) or thiothixene 10 mg X 3 (N = 34) USING A DOUBLE-BLIND PROCEDURE. Before and during treatment, levels of HVA, MOPEG, and 5-HIAA, the major metabolites of DA, NE, and 5-HT, were determined in lumbar cerebrospinal fluid by a mass fragmentographic technique. Both treatments resulted in an elevation of the HVA levels after 2 weeks, thiothixene having a more marked effect. The effect of thiothixene but not of melperone persisted after 4 weeks. Thiothixene did not influence the MOPEG level, but melperone reduced it after 4 weeks of treatment. The 5-HIAA levels were not significantly altered by the drugs. The HVA/MOPEG and the HVA/5-HIAA ratios were highly significantly elevated by both drugs after 2 as well as 4 weeks. Thiothixene induced a significantly greater change of these ratios than melperone. The results supply evidence that thiothixene accelerates central dopamine metabolism in man, presumably by blocking DA receptors. Melperone appears to act similarly, but has an effect which is weaker and/or of shorter duration. During long-term treatment with melperone the receptors develop tolerance to it. The acceleration in DA metabolism declines and the effect of melperone switches instead to central NA metabolism. The results indicate that both drugs cause long-term changes in the activity ratios of central monoamine systems. It is suggested that such changes in several systems rather than single biochemical events may be related to the antipsychotic effects of neuroleptic drugs. This study also demonstrated the versatility of using monoamine metabolite analysis of the CSF as a tool for the quantification of biochemical effects of neuroleptic drugs on the human CNS.", "contents": "Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with melperone or thiothixene. Psychotic women with schizophrenic symptoms were treated with melperone 100 mg X 3 (n = 29) or thiothixene 10 mg X 3 (N = 34) USING A DOUBLE-BLIND PROCEDURE. Before and during treatment, levels of HVA, MOPEG, and 5-HIAA, the major metabolites of DA, NE, and 5-HT, were determined in lumbar cerebrospinal fluid by a mass fragmentographic technique. Both treatments resulted in an elevation of the HVA levels after 2 weeks, thiothixene having a more marked effect. The effect of thiothixene but not of melperone persisted after 4 weeks. Thiothixene did not influence the MOPEG level, but melperone reduced it after 4 weeks of treatment. The 5-HIAA levels were not significantly altered by the drugs. The HVA/MOPEG and the HVA/5-HIAA ratios were highly significantly elevated by both drugs after 2 as well as 4 weeks. Thiothixene induced a significantly greater change of these ratios than melperone. The results supply evidence that thiothixene accelerates central dopamine metabolism in man, presumably by blocking DA receptors. Melperone appears to act similarly, but has an effect which is weaker and/or of shorter duration. During long-term treatment with melperone the receptors develop tolerance to it. The acceleration in DA metabolism declines and the effect of melperone switches instead to central NA metabolism. The results indicate that both drugs cause long-term changes in the activity ratios of central monoamine systems. It is suggested that such changes in several systems rather than single biochemical events may be related to the antipsychotic effects of neuroleptic drugs. This study also demonstrated the versatility of using monoamine metabolite analysis of the CSF as a tool for the quantification of biochemical effects of neuroleptic drugs on the human CNS."}
{"id": "PMID:21645", "title": "Adult cryptorchids: Sexual development and activity.", "content": "Plasma testosterone in 72 unilateral and 83 bilateral cryptorchids, 11-45 years of age, revealed that, from 13 years on , values of male hormone were lower than in the control group of 69 normal boys and 85 fertile and potent men. Analysis of heterosexual development by means of the HTDM questionnaire in 49 unilateral and 57 bilateral cryptorchids, aged 21-40 years, who were examined for sterility, revealed only slight social developmental retardation compared to 184 normospermic men from sterile marriages. On the other hand, examination of sexual activity by means of the SAM questionnaire in the same three groups revealed that in cryptorchids the first ejaculation is slightly later and that the frequency of nocturnal emissions in pubescence is lower. In adulthood the patients with cryptorchidism exhibit fewer signs of high sexual activity suca as repeated coitus on the same day or a high frequency of sexual intercourse. Also, there is an earlier appearance of prolonged periods of sexual abstinence.", "contents": "Adult cryptorchids: Sexual development and activity. Plasma testosterone in 72 unilateral and 83 bilateral cryptorchids, 11-45 years of age, revealed that, from 13 years on , values of male hormone were lower than in the control group of 69 normal boys and 85 fertile and potent men. Analysis of heterosexual development by means of the HTDM questionnaire in 49 unilateral and 57 bilateral cryptorchids, aged 21-40 years, who were examined for sterility, revealed only slight social developmental retardation compared to 184 normospermic men from sterile marriages. On the other hand, examination of sexual activity by means of the SAM questionnaire in the same three groups revealed that in cryptorchids the first ejaculation is slightly later and that the frequency of nocturnal emissions in pubescence is lower. In adulthood the patients with cryptorchidism exhibit fewer signs of high sexual activity suca as repeated coitus on the same day or a high frequency of sexual intercourse. Also, there is an earlier appearance of prolonged periods of sexual abstinence."}
{"id": "PMID:21646", "title": "[Ultrastructure of B-cell tumors of the pancreas (insulinomas - insular carcinoid tumors)].", "content": "The subcellular organization of 6 B-cell tumours of the human pancreas was studied. The tumour parenchyma consisted of processed light, dark, and moderately electron dense cells containing insulin granules. The presence of villi in the cytoplasm of tumour cells and intranuclear fibrills was demonstrated. The participation of tumour cells in formation of amyloid-like thin-fiber substance filling the intercellular and perivascular spaces was established. The similarity between endothelial cells of tumour vessels and parenchymatous cells was shown. A hypothesis on neuroectodermal origin of the endocrine tissue of the pancreas is supported.", "contents": "[Ultrastructure of B-cell tumors of the pancreas (insulinomas - insular carcinoid tumors)]. The subcellular organization of 6 B-cell tumours of the human pancreas was studied. The tumour parenchyma consisted of processed light, dark, and moderately electron dense cells containing insulin granules. The presence of villi in the cytoplasm of tumour cells and intranuclear fibrills was demonstrated. The participation of tumour cells in formation of amyloid-like thin-fiber substance filling the intercellular and perivascular spaces was established. The similarity between endothelial cells of tumour vessels and parenchymatous cells was shown. A hypothesis on neuroectodermal origin of the endocrine tissue of the pancreas is supported."}
{"id": "PMID:21648", "title": "Polyarteritis nodosa and deafness. A human temporal bone study.", "content": "Temporal bone changes were described in a 66 year old woman with polyarteritis nodosa who became deaf 7 months before death. Polyarteritis nodosa of the left internal auditory artery was demonstrated with fibrosis and bone formation involving the cochlea and vestibular system. Endolymphatic hydrops of the basal turn of the cochlea was also present, as well as a chronic perforation of the free wall of the saccule.", "contents": "Polyarteritis nodosa and deafness. A human temporal bone study. Temporal bone changes were described in a 66 year old woman with polyarteritis nodosa who became deaf 7 months before death. Polyarteritis nodosa of the left internal auditory artery was demonstrated with fibrosis and bone formation involving the cochlea and vestibular system. Endolymphatic hydrops of the basal turn of the cochlea was also present, as well as a chronic perforation of the free wall of the saccule."}
{"id": "PMID:21652", "title": "Biochemical and genetic factors in the heat inactivation of murine beta-glucuronidase.", "content": "The enzymes coded for by two alleles at the glucuronidase structural locus (Gus) were compared in their response to pH, buffering anion, buffer molarity, ionic strength, and temperature. The heat-labile Gush gene product responded in a qualitatively similar but quantitatively reduced manner compared to the relatively heat-stable Gusb gene product. In all buffers tested, the enzyme was most heat stable at pH 5.0. Ranking of the various buffer anions tested, according to increasing heat stabilization, was water less than acetate less than or equal to phosphate less than citrate. Varying the molarity of the buffers from 0.01 to 0.6 M at pH 5.0 revealed further differences among the buffers. Increasing ionic strength exerted a destabilizing force on the protein. The half-life of the enzyme decreased by as much as a hundredfold between 71 and 75 C. The Gush/Gush genotype also results in decreased activity levels in all tissues, reportedly because of decreased synthesis. The heat inactivation curves of Gusb/Gush heterozygotes were incompatible with any theoretical curve based on the assumption that the Gusb and Gush chromosomes in the heterozygote behave in a manner similar to that seen in the homozygotes.", "contents": "Biochemical and genetic factors in the heat inactivation of murine beta-glucuronidase. The enzymes coded for by two alleles at the glucuronidase structural locus (Gus) were compared in their response to pH, buffering anion, buffer molarity, ionic strength, and temperature. The heat-labile Gush gene product responded in a qualitatively similar but quantitatively reduced manner compared to the relatively heat-stable Gusb gene product. In all buffers tested, the enzyme was most heat stable at pH 5.0. Ranking of the various buffer anions tested, according to increasing heat stabilization, was water less than acetate less than or equal to phosphate less than citrate. Varying the molarity of the buffers from 0.01 to 0.6 M at pH 5.0 revealed further differences among the buffers. Increasing ionic strength exerted a destabilizing force on the protein. The half-life of the enzyme decreased by as much as a hundredfold between 71 and 75 C. The Gush/Gush genotype also results in decreased activity levels in all tissues, reportedly because of decreased synthesis. The heat inactivation curves of Gusb/Gush heterozygotes were incompatible with any theoretical curve based on the assumption that the Gusb and Gush chromosomes in the heterozygote behave in a manner similar to that seen in the homozygotes."}
{"id": "PMID:21653", "title": "Studies on the female sterile mutant rudimentary of Drosophila melanogaster. II. An analysis of aspartate transcarbamylase and dihydroorotase activities in wild-type and rudimentary strains.", "content": "The activities of the enzymes aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) were determined in adult females from a wild-type strain and from eight different alleles of the X-linked mutation rudimentary (r) of Drosophila melanogaster. The alleles chosen span the genetic map of the r locus. The characteristics of the DHOase-catalyzed reaction which converts carbamyl aspartate to dehydroorotate are briefly described. Of all of the r strains tested, only one, r9, has wild-type levels of aspartate transcarbamylase and dihydroorotase activities. The other seven show either intermediate or very low levels of activity for both enzymes. The lowered ATCase and DHOase activities observed in mutants which do not map in the region of the structural gene for these enzymes are interpreted in light of recent evidence that ATCase and DHOase are part of a three-enzyme complex.", "contents": "Studies on the female sterile mutant rudimentary of Drosophila melanogaster. II. An analysis of aspartate transcarbamylase and dihydroorotase activities in wild-type and rudimentary strains. The activities of the enzymes aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) were determined in adult females from a wild-type strain and from eight different alleles of the X-linked mutation rudimentary (r) of Drosophila melanogaster. The alleles chosen span the genetic map of the r locus. The characteristics of the DHOase-catalyzed reaction which converts carbamyl aspartate to dehydroorotate are briefly described. Of all of the r strains tested, only one, r9, has wild-type levels of aspartate transcarbamylase and dihydroorotase activities. The other seven show either intermediate or very low levels of activity for both enzymes. The lowered ATCase and DHOase activities observed in mutants which do not map in the region of the structural gene for these enzymes are interpreted in light of recent evidence that ATCase and DHOase are part of a three-enzyme complex."}
{"id": "PMID:21654", "title": "Properties of soluble somatostatin-binding protein.", "content": "A soluble somatostatin-binding protein was detected in the cytosol fractions of various rat, human and bovine tissues. Maximum binding occurred at pH8.0-8.5 and was Ca(2+)-dependent. The specific binding of somatostatin per 10mug of cytosol protein from 12 rat tissues ranged between 36 and 15%, and 3% for peripheral blood cells. There was also substantial binding in cytosol from human anterior pituitary and liver, and bovine anterior pituitary. The specific binding in rat and human plasma in the presence of EDTA was only 1%. Gel filtration suggested a molecular weight of approx. 80000 for the somatostatin-binding protein from several sources. Exposure of the binding protein to trypsin eliminates somatostatin-binding activity but ribonuclease and deoxyribonuclease have no effect. The binding protein is thermolabile, ethanol-precipitable, and not completely specific for somatostatin. Bound (125)I-labelled [Tyr(1)]somatostatin is not easily displaced by excess of unlabelled somatostatin. The effects of dithiothreitol and mercaptoethanol on the binding of (125)I-labelled [Tyr(1)]somatostatin to the binding protein suggests that binding involves two sequential steps, first loose binding, then disulphide linkage. Since semipurified somatostatin-binding protein causes a dose-related inhibition of the binding of (125)I-labelled [Tyr(1)]somatostatin in radioimmunoassays for somatostatin, estimates of somatostatin content of tissue extracts by radioimmunoassay in some cases may be spuriously high. It is not yet clear whether the binding protein is a true cytosol protein or an easily solubilized membrane protein.", "contents": "Properties of soluble somatostatin-binding protein. A soluble somatostatin-binding protein was detected in the cytosol fractions of various rat, human and bovine tissues. Maximum binding occurred at pH8.0-8.5 and was Ca(2+)-dependent. The specific binding of somatostatin per 10mug of cytosol protein from 12 rat tissues ranged between 36 and 15%, and 3% for peripheral blood cells. There was also substantial binding in cytosol from human anterior pituitary and liver, and bovine anterior pituitary. The specific binding in rat and human plasma in the presence of EDTA was only 1%. Gel filtration suggested a molecular weight of approx. 80000 for the somatostatin-binding protein from several sources. Exposure of the binding protein to trypsin eliminates somatostatin-binding activity but ribonuclease and deoxyribonuclease have no effect. The binding protein is thermolabile, ethanol-precipitable, and not completely specific for somatostatin. Bound (125)I-labelled [Tyr(1)]somatostatin is not easily displaced by excess of unlabelled somatostatin. The effects of dithiothreitol and mercaptoethanol on the binding of (125)I-labelled [Tyr(1)]somatostatin to the binding protein suggests that binding involves two sequential steps, first loose binding, then disulphide linkage. Since semipurified somatostatin-binding protein causes a dose-related inhibition of the binding of (125)I-labelled [Tyr(1)]somatostatin in radioimmunoassays for somatostatin, estimates of somatostatin content of tissue extracts by radioimmunoassay in some cases may be spuriously high. It is not yet clear whether the binding protein is a true cytosol protein or an easily solubilized membrane protein."}
{"id": "PMID:21655", "title": "Microbial metabolism of aromatic nitriles. Enzymology of C-N cleavage by Nocardia sp. (Rhodochrous group) N.C.I.B. 11216.", "content": "1. An organism utilizing benzonitrile as sole carbon and nitrogen source was isolated by the enrichment-culture technique and identified as a Nocardia sp. of the rhodochrous group. 2. Respiration studies indicate that nitrile degradation proceeds through benzoic acid and catechol. 3. Cell-free extracts of benzonitrile-grown cells contain an enzyme that catalyses the conversion of benzonitrile directly into benzoic acid without intermediate formation of benzamide. 4. This nitrilase enzyme was purified by DEAE-cellulose chromatography and gel filtration on Sephadex G-100 in the presence and absence of substrate. The purity of the enzyme was confirmed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and isoelectric focusing on polyacrylamide gel. 5. The enzyme shows a time-dependent substrate-activation process in which the substrate catalyses the association of inactive subunits of mol.wt. 45000 to form the polymeric 12-unit active enzyme of mol.wt. 560000. The time required for complete association is highly dependent on the concentration of the enzyme, temperature and pH. 6. The associated enzyme has a pH optimum of 8.0 and K(m) with benzonitrile as substrate of 4mm. The activation energy of the reaction as deduced from the Arrhenius plot is 51.8kJ/mol. 7. Enzyme activity is inhibited by thiol-specific reagents and several metal ions. 8. Studies with different substrates indicate that the nitrilase is specific for nitrile groups directly attached to the benzene ring. Various substituents in the ring are compatible with activity, though ortho-substitution, except by fluorine, renders the nitrile invulnerable to attack. 9. The environmental implications of these findings and the possible significance of the enzyme in the regulation of metabolism are discussed.", "contents": "Microbial metabolism of aromatic nitriles. Enzymology of C-N cleavage by Nocardia sp. (Rhodochrous group) N.C.I.B. 11216. 1. An organism utilizing benzonitrile as sole carbon and nitrogen source was isolated by the enrichment-culture technique and identified as a Nocardia sp. of the rhodochrous group. 2. Respiration studies indicate that nitrile degradation proceeds through benzoic acid and catechol. 3. Cell-free extracts of benzonitrile-grown cells contain an enzyme that catalyses the conversion of benzonitrile directly into benzoic acid without intermediate formation of benzamide. 4. This nitrilase enzyme was purified by DEAE-cellulose chromatography and gel filtration on Sephadex G-100 in the presence and absence of substrate. The purity of the enzyme was confirmed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and isoelectric focusing on polyacrylamide gel. 5. The enzyme shows a time-dependent substrate-activation process in which the substrate catalyses the association of inactive subunits of mol.wt. 45000 to form the polymeric 12-unit active enzyme of mol.wt. 560000. The time required for complete association is highly dependent on the concentration of the enzyme, temperature and pH. 6. The associated enzyme has a pH optimum of 8.0 and K(m) with benzonitrile as substrate of 4mm. The activation energy of the reaction as deduced from the Arrhenius plot is 51.8kJ/mol. 7. Enzyme activity is inhibited by thiol-specific reagents and several metal ions. 8. Studies with different substrates indicate that the nitrilase is specific for nitrile groups directly attached to the benzene ring. Various substituents in the ring are compatible with activity, though ortho-substitution, except by fluorine, renders the nitrile invulnerable to attack. 9. The environmental implications of these findings and the possible significance of the enzyme in the regulation of metabolism are discussed."}
{"id": "PMID:21656", "title": "Kinetic properties of a magnesium ion- and calcium ion-stimulated adenosine triphosphatase from the outer-membrane fraction of rat spleen mitochondria.", "content": "1. Isolated outer membranes from rat spleen mitochondria can be stored in liquid N(2) for several weeks without significant loss of ATPase (adenosine triphosphatase) activity. 2. The ATPase reaction has a broad pH optimum centering on neutral pH, with little significant activity above pH9.0 or below pH5.5. 3. A sigmoidal response of the ATPase activity to temperature is observed between 0 and 55 degrees C, with complete inactivation at 60 degrees C. The Arrhenius plot shows that the activation energy above the transition temperature (22 degrees C) (E(a)=144kJ/mol) is one-third of that calculated for below the transition temperature (E'(a)=408kJ/mol). 4. The outer-membrane ATPase (K(m) for MgATP=50mum) is inactive unless Mg(2+) is added, whereas the inner-membrane ATPase (K(m) for ATP=11mum) is active without added Mg(2+) unless the mitochondria have been depleted of all endogenous Mg(2+) (by using ionophore A23187). 5. The substrate for the outer-membrane ATPase is a bivalent metal ion-nucleoside triphosphate complex in which Mg(2+) (K(m)=50mum) can be replaced effectively by Ca(2+) (K(m)=6.7mum) or Mn(2+), and ATP by ITP. Cu(2+), Co(2+), Sr(2+), Ba(2+), Ni(2+), Cd(2+) and Zn(2+) support very little ATP hydrolysis. 6. Univalent metal ions (Na(+), K(+), Rb(+), Cs(+) and NH(4) (+), but not Li(+)) stimulate the MgATPase activity (<10%) at low concentrations (50mm), but, except for K(+), are slightly inhibitory (20-30%) at higher concentrations (500mm). 7. The Mg(2+)-stimulated ATPase activity is significantly inhibited by Cu(2+) (K(i)=90mum), Ni(2+) (K(i)=510mum), Zn(2+) (K(i)=680mum) and Co(2+) (K(i)=1020mum), but not by Mg(2+), Ca(2+), Ba(2+) or Sr(2+). 8. The outer-membrane ATPase is insensitive to the inhibitors oligomycin, NN'-dicyclohexylcarbodiimide, NaN(3), ouabain and thiol-specific reagents. A significant inhibition is observed at high concentrations of AgNO(3) (0.5mm) and NaF (10mm). 9. The activity towards MgATP is competitively inhibited by the product MgADP (K(i)=0.7mm) but not by the second product P(i) or by 5'-AMP.", "contents": "Kinetic properties of a magnesium ion- and calcium ion-stimulated adenosine triphosphatase from the outer-membrane fraction of rat spleen mitochondria. 1. Isolated outer membranes from rat spleen mitochondria can be stored in liquid N(2) for several weeks without significant loss of ATPase (adenosine triphosphatase) activity. 2. The ATPase reaction has a broad pH optimum centering on neutral pH, with little significant activity above pH9.0 or below pH5.5. 3. A sigmoidal response of the ATPase activity to temperature is observed between 0 and 55 degrees C, with complete inactivation at 60 degrees C. The Arrhenius plot shows that the activation energy above the transition temperature (22 degrees C) (E(a)=144kJ/mol) is one-third of that calculated for below the transition temperature (E'(a)=408kJ/mol). 4. The outer-membrane ATPase (K(m) for MgATP=50mum) is inactive unless Mg(2+) is added, whereas the inner-membrane ATPase (K(m) for ATP=11mum) is active without added Mg(2+) unless the mitochondria have been depleted of all endogenous Mg(2+) (by using ionophore A23187). 5. The substrate for the outer-membrane ATPase is a bivalent metal ion-nucleoside triphosphate complex in which Mg(2+) (K(m)=50mum) can be replaced effectively by Ca(2+) (K(m)=6.7mum) or Mn(2+), and ATP by ITP. Cu(2+), Co(2+), Sr(2+), Ba(2+), Ni(2+), Cd(2+) and Zn(2+) support very little ATP hydrolysis. 6. Univalent metal ions (Na(+), K(+), Rb(+), Cs(+) and NH(4) (+), but not Li(+)) stimulate the MgATPase activity (<10%) at low concentrations (50mm), but, except for K(+), are slightly inhibitory (20-30%) at higher concentrations (500mm). 7. The Mg(2+)-stimulated ATPase activity is significantly inhibited by Cu(2+) (K(i)=90mum), Ni(2+) (K(i)=510mum), Zn(2+) (K(i)=680mum) and Co(2+) (K(i)=1020mum), but not by Mg(2+), Ca(2+), Ba(2+) or Sr(2+). 8. The outer-membrane ATPase is insensitive to the inhibitors oligomycin, NN'-dicyclohexylcarbodiimide, NaN(3), ouabain and thiol-specific reagents. A significant inhibition is observed at high concentrations of AgNO(3) (0.5mm) and NaF (10mm). 9. The activity towards MgATP is competitively inhibited by the product MgADP (K(i)=0.7mm) but not by the second product P(i) or by 5'-AMP."}
{"id": "PMID:21657", "title": "Evidence for two-step binding of reduced nicotinamide-adenine dinucleotide to aldehyde dehydrogenase.", "content": "The displacement of NADH from cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) from sheep liver was studied by using NAD+, 1,10-phenanthroline, ADP-ribose, deamino-NAD+ and pyridine-3-aldehyde-adenine dinucleotide as displacing agents, by following the decrease in fluorescence as a function of time. The data obtained could be fitted by assuming two first-order processes were occurring, a faster process with an apparent rate constant of 0.85 +/- 0.20 s-1 and a relative amplitude of 60 +/- 10% and a slower process with an apparent rate constant of 0.20 +/- 0.05 s-1 and a relative amplitude of 40 +/- 10% (except for pyridine-3-aldehyde-adenine dinucleotide, where the apparent rate constant for the slow process was 0.05 s-1). The displacement rates did not change significantly when the pH was varied from 6.0 to 9.0. Kinetic data are also reported for the dependence of the rate of binding of NADH to the enzyme on the total concentration of NADH. Detailed arguments are presented based on the isolation and purification procedures, the equilibrium coenzyme-binding studies and the kinetic data, which lead to the following model for the release of NADH from the enzyme: (formula: see article). The parameters that best fit the data are: k + 1 = 0.2 s-1; k - 1 = 0.05 s-1; k + 2 = 0.8 s-1 and k - 2 = 5 X 10(5)litre-mol-1-s-1. The slow phase of the NADH release is similar to the steady-state turnover number for substrates such as acetaldehyde and propionaldehyde and appears to contribute significantly to the limitation of the steady-state rate.", "contents": "Evidence for two-step binding of reduced nicotinamide-adenine dinucleotide to aldehyde dehydrogenase. The displacement of NADH from cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) from sheep liver was studied by using NAD+, 1,10-phenanthroline, ADP-ribose, deamino-NAD+ and pyridine-3-aldehyde-adenine dinucleotide as displacing agents, by following the decrease in fluorescence as a function of time. The data obtained could be fitted by assuming two first-order processes were occurring, a faster process with an apparent rate constant of 0.85 +/- 0.20 s-1 and a relative amplitude of 60 +/- 10% and a slower process with an apparent rate constant of 0.20 +/- 0.05 s-1 and a relative amplitude of 40 +/- 10% (except for pyridine-3-aldehyde-adenine dinucleotide, where the apparent rate constant for the slow process was 0.05 s-1). The displacement rates did not change significantly when the pH was varied from 6.0 to 9.0. Kinetic data are also reported for the dependence of the rate of binding of NADH to the enzyme on the total concentration of NADH. Detailed arguments are presented based on the isolation and purification procedures, the equilibrium coenzyme-binding studies and the kinetic data, which lead to the following model for the release of NADH from the enzyme: (formula: see article). The parameters that best fit the data are: k + 1 = 0.2 s-1; k - 1 = 0.05 s-1; k + 2 = 0.8 s-1 and k - 2 = 5 X 10(5)litre-mol-1-s-1. The slow phase of the NADH release is similar to the steady-state turnover number for substrates such as acetaldehyde and propionaldehyde and appears to contribute significantly to the limitation of the steady-state rate."}
{"id": "PMID:21658", "title": "Purification and some properties of 1-aspartamido-beta-N-acetylglucosamine amidohydrolase from human liver.", "content": "Human liver 1-aspartamido-beta-N-acetylglucosamine amidohydrolase (aspartylglucosylaminase, EC 3.5.1.26) was purified 17 500-fold to apparent homogeneity as judged from polyacrylamide-gel disc electrophoresis. A pH optimum of 7.7-9.0 was found. The Km value was pH- and temperature-dependent. At 37 degrees C and pH 7.7, Km was 0.16 mM and it increased to 0.29 at pH 6.0 and 0.23 at pH 9.0. At 25 degrees C and pH 7.7, a Km value of 0.99 mM was obtained. When the substrate concentration was varied, apparent Michaelis-Menten kinetics were obtained. p-Hydroxymercuribenzoate, glutathione or cysteine had no effect on the enzyme activity; 5 mM-N-acetylcysteine inhibited about 47% of the total enzyme activity. Apart from Cu2+, other bivalent ions were virtually ineffective at 1 mM. The kinetic study differentiates this enzyme from aspartylglucosylaminase from other sources.", "contents": "Purification and some properties of 1-aspartamido-beta-N-acetylglucosamine amidohydrolase from human liver. Human liver 1-aspartamido-beta-N-acetylglucosamine amidohydrolase (aspartylglucosylaminase, EC 3.5.1.26) was purified 17 500-fold to apparent homogeneity as judged from polyacrylamide-gel disc electrophoresis. A pH optimum of 7.7-9.0 was found. The Km value was pH- and temperature-dependent. At 37 degrees C and pH 7.7, Km was 0.16 mM and it increased to 0.29 at pH 6.0 and 0.23 at pH 9.0. At 25 degrees C and pH 7.7, a Km value of 0.99 mM was obtained. When the substrate concentration was varied, apparent Michaelis-Menten kinetics were obtained. p-Hydroxymercuribenzoate, glutathione or cysteine had no effect on the enzyme activity; 5 mM-N-acetylcysteine inhibited about 47% of the total enzyme activity. Apart from Cu2+, other bivalent ions were virtually ineffective at 1 mM. The kinetic study differentiates this enzyme from aspartylglucosylaminase from other sources."}
{"id": "PMID:21659", "title": "Effect of substrates and effectors on the reversible inactivation of pig spleen phosphofructokinase by adenosine triphosphate.", "content": "1. To investigate the mechanism of the reversible inactivation of pig spleen phosphofructokinase by ATP, the effect of order of addition of reactants (substrates, effectors and enzyme solution) was studied by preincubating the enzyme before assay with various combinations of its substrates and effectors. 2. Preincubation of the enzyme with MgATP or ATP at pH7.0 before addition of fructose 6-phosphate caused a rapid and much greater inhibition of activity than that observed when the reaction (carried out at identical substrate concentrations) was initiated with enzyme. 3. The rapid inhibition caused by preincubation with ATP, together with the sigmoidal response to fructose 6-phosphate and activation by AMP, were all blocked by prior photo-oxidation of the enzyme with Methylene Blue, which selectively destroys the inhibitory binding site for ATP [Ahlfors & Mansour (1969) J. Biol. Chem.244, 1247-1251]. 4. Fructose 6-phosphate, but not Mg(2+), protected phosphofructokinase from inhibition during preincubation with ATP in a manner that was sigmoidally dependent on the fructose 6-phosphate concentration. 5. Mg(2+), by protecting the enzyme from the inhibitory effect of preincubation at low pH (7.0) and by preventing its activation during preincubation with fructose 6-phosphate, demonstrated both a weak activating effect in the absence of the other substrates and a stronger inhibitory effect in the presence of fructose 6-phosphate. 6. Positive effectors (K(+), NH(4) (+), AMP and aspartate) protected the enzyme from inhibition during preincubation with MgATP in proportion to their potency as activators, but citrate potentiated the ATP inhibition. P(i) significantly slowed the inactivation process without itself acting as a positive effector. 7. The non-linear dependence of the initial rate of the unmodified enzyme on protein concentration (associated with increased positive homotropic co-operativity to fructose 6-phosphate) was intensified by preincubation with ATP and abolished by photo-oxidation. 8. The results are interpreted in terms of an association-dissociation model which postulates that protonation, at low pH, of a photo-oxidation-sensitive inhibitory site for ATP allows more rapid dissociation of an active tetramer to an inactive dimeric species.", "contents": "Effect of substrates and effectors on the reversible inactivation of pig spleen phosphofructokinase by adenosine triphosphate. 1. To investigate the mechanism of the reversible inactivation of pig spleen phosphofructokinase by ATP, the effect of order of addition of reactants (substrates, effectors and enzyme solution) was studied by preincubating the enzyme before assay with various combinations of its substrates and effectors. 2. Preincubation of the enzyme with MgATP or ATP at pH7.0 before addition of fructose 6-phosphate caused a rapid and much greater inhibition of activity than that observed when the reaction (carried out at identical substrate concentrations) was initiated with enzyme. 3. The rapid inhibition caused by preincubation with ATP, together with the sigmoidal response to fructose 6-phosphate and activation by AMP, were all blocked by prior photo-oxidation of the enzyme with Methylene Blue, which selectively destroys the inhibitory binding site for ATP [Ahlfors & Mansour (1969) J. Biol. Chem.244, 1247-1251]. 4. Fructose 6-phosphate, but not Mg(2+), protected phosphofructokinase from inhibition during preincubation with ATP in a manner that was sigmoidally dependent on the fructose 6-phosphate concentration. 5. Mg(2+), by protecting the enzyme from the inhibitory effect of preincubation at low pH (7.0) and by preventing its activation during preincubation with fructose 6-phosphate, demonstrated both a weak activating effect in the absence of the other substrates and a stronger inhibitory effect in the presence of fructose 6-phosphate. 6. Positive effectors (K(+), NH(4) (+), AMP and aspartate) protected the enzyme from inhibition during preincubation with MgATP in proportion to their potency as activators, but citrate potentiated the ATP inhibition. P(i) significantly slowed the inactivation process without itself acting as a positive effector. 7. The non-linear dependence of the initial rate of the unmodified enzyme on protein concentration (associated with increased positive homotropic co-operativity to fructose 6-phosphate) was intensified by preincubation with ATP and abolished by photo-oxidation. 8. The results are interpreted in terms of an association-dissociation model which postulates that protonation, at low pH, of a photo-oxidation-sensitive inhibitory site for ATP allows more rapid dissociation of an active tetramer to an inactive dimeric species."}
{"id": "PMID:21667", "title": "[Synthesis and physico-chemical properties of the antihypertensive agent urapidil (author's transl)].", "content": "6-(3-[4-(o-Methoxyphenyl)-1-piperazinyl]-propylamino)-1,3-dimethyluracil (Urapidil, Ebrantil) is a new antihypertensive agent whose synthesis and physico-chemical properties are described. The size of the permeation constant KD of the passive transport through collodion-lecithin membranes and the value of the partition coefficient P in the neutral area indicate a good absorption and uniform distribution of the substance in the organism.", "contents": "[Synthesis and physico-chemical properties of the antihypertensive agent urapidil (author's transl)]. 6-(3-[4-(o-Methoxyphenyl)-1-piperazinyl]-propylamino)-1,3-dimethyluracil (Urapidil, Ebrantil) is a new antihypertensive agent whose synthesis and physico-chemical properties are described. The size of the permeation constant KD of the passive transport through collodion-lecithin membranes and the value of the partition coefficient P in the neutral area indicate a good absorption and uniform distribution of the substance in the organism."}
{"id": "PMID:21668", "title": "Effect of dihydroergotoxine on activities of beta-receptor stimulators.", "content": "The effect of dihydroergotoxine (DET), an alpha-receptor blocker, on the bronchodilating effect of various beta-receptor stimulators was examined using the isolated guinea-pig tracheal smooth muscle. Relaxation of isolated guinea-pig tracheal smooth muscle with isoproterenol hydrochloride, salbutamol hemisulfate and clorprenaline hydrochloride, was markedly increased by continous infusion of DET. This result may suggest that DET, an alpha-receptor blocker, can be used together with bronchodilators such as beta-receptor stimulator for the treatment of various chronic obstructive pulmonary diseases.", "contents": "Effect of dihydroergotoxine on activities of beta-receptor stimulators. The effect of dihydroergotoxine (DET), an alpha-receptor blocker, on the bronchodilating effect of various beta-receptor stimulators was examined using the isolated guinea-pig tracheal smooth muscle. Relaxation of isolated guinea-pig tracheal smooth muscle with isoproterenol hydrochloride, salbutamol hemisulfate and clorprenaline hydrochloride, was markedly increased by continous infusion of DET. This result may suggest that DET, an alpha-receptor blocker, can be used together with bronchodilators such as beta-receptor stimulator for the treatment of various chronic obstructive pulmonary diseases."}
{"id": "PMID:21669", "title": "A study of antidepressant activity of some indole alkylamines.", "content": "The antidepressant characteristics of three indole alkylamines were investigated and compared with phenelzine and imipramine by utilising specific pharmacological tools like reserpine, amphetamine, tryptamine and tetrabenazine for determining their possible mechanism of action. Amongst the three indole compounds investigated, indole-3-(2-aminopropyl)-acetate (U-14 164E), indole-3(2-aminobutyl)-d-acetate (u-17 312E) and beta-phenethylhydrazine (phenelzine) produced complete antagonism to reserpine induced sedation, hypothermia as well as facilitation of convulsive seizures. Some of these features suggest that MAO inhibition might be a common mechanism of action of these indoles. The potentiation of CNS effects of tryptamine by these compounds is an outstanding feature of MAO inhibitors, while imipramine is ineffective. Qualitative differences between these indoles and imipramine are evident in the tetrabenazine test. The potentiation of amphetamine induced motor excitation and pentobarbitone narcosis has been explained.", "contents": "A study of antidepressant activity of some indole alkylamines. The antidepressant characteristics of three indole alkylamines were investigated and compared with phenelzine and imipramine by utilising specific pharmacological tools like reserpine, amphetamine, tryptamine and tetrabenazine for determining their possible mechanism of action. Amongst the three indole compounds investigated, indole-3-(2-aminopropyl)-acetate (U-14 164E), indole-3(2-aminobutyl)-d-acetate (u-17 312E) and beta-phenethylhydrazine (phenelzine) produced complete antagonism to reserpine induced sedation, hypothermia as well as facilitation of convulsive seizures. Some of these features suggest that MAO inhibition might be a common mechanism of action of these indoles. The potentiation of CNS effects of tryptamine by these compounds is an outstanding feature of MAO inhibitors, while imipramine is ineffective. Qualitative differences between these indoles and imipramine are evident in the tetrabenazine test. The potentiation of amphetamine induced motor excitation and pentobarbitone narcosis has been explained."}
{"id": "PMID:21671", "title": "Bioavailability of quinidine in slow-release form. A comparison between two preparations containing quinidine bisulphate as the active constituent.", "content": "Two different slow-release preparations of quinidine bisulphate (A and B) have been tested. The in vitro dissolution rate of preparation B was substantially lower in intestinal than in gastric juice, whereas the release rate of quinidine from preparation A was virtually unaffected by the pH of the dissolution medium. After a single dose of two tablets of each of the preparations to 6 healthy volunteers, corresponding to 386 mg (B) and 320 mg of quinidine base (A), the maximum plasma concentration was attained after about 4.5 h. The peak concentration was 5.2 +/- 0.5 mumol/l for preparation A and 4.1 +/- 0.4 mumol/l for B. A similar difference was found in the area under the plasma concentration curve (AUC), which was 68 +/- 10 mumol-h/l and 54 +/- 5 mumol-h/l, respectively. Taking into consideration that preparation B contained 20.6% more active drug per tablet these values indicate that the extent of bioavailability is about 50% higher for tablet A than for tablet B.", "contents": "Bioavailability of quinidine in slow-release form. A comparison between two preparations containing quinidine bisulphate as the active constituent. Two different slow-release preparations of quinidine bisulphate (A and B) have been tested. The in vitro dissolution rate of preparation B was substantially lower in intestinal than in gastric juice, whereas the release rate of quinidine from preparation A was virtually unaffected by the pH of the dissolution medium. After a single dose of two tablets of each of the preparations to 6 healthy volunteers, corresponding to 386 mg (B) and 320 mg of quinidine base (A), the maximum plasma concentration was attained after about 4.5 h. The peak concentration was 5.2 +/- 0.5 mumol/l for preparation A and 4.1 +/- 0.4 mumol/l for B. A similar difference was found in the area under the plasma concentration curve (AUC), which was 68 +/- 10 mumol-h/l and 54 +/- 5 mumol-h/l, respectively. Taking into consideration that preparation B contained 20.6% more active drug per tablet these values indicate that the extent of bioavailability is about 50% higher for tablet A than for tablet B."}
{"id": "PMID:21677", "title": "Flunitrazepam compared with althesin as an induction agent in balanced anaesthesia.", "content": "The effects of flunitrazepam and Althesin as anaesthetic induction agents were studied in a double-blind trial in 97 patients undergoing abdominal or gynaecological surgery. There was no difference between the two preparations in respect of the quality of induction. A marked difference in the quality of maintenance of anaesthesia were seen, in favour of flunitrazepam. Recovery was more rapid from Althesin anaesthesia. A low incidence of nausea was observed in both groups.", "contents": "Flunitrazepam compared with althesin as an induction agent in balanced anaesthesia. The effects of flunitrazepam and Althesin as anaesthetic induction agents were studied in a double-blind trial in 97 patients undergoing abdominal or gynaecological surgery. There was no difference between the two preparations in respect of the quality of induction. A marked difference in the quality of maintenance of anaesthesia were seen, in favour of flunitrazepam. Recovery was more rapid from Althesin anaesthesia. A low incidence of nausea was observed in both groups."}
{"id": "PMID:21678", "title": "Studies of drugs given before anaesthesia XXVI: lorazepam.", "content": "Lorazepam has been studied as preanaesthetic medication given by mouth, i.m. and i.v. Sediation and side-effects and the incidence of anterograde amnesia in patients having a standard operation under methohexitone-nitrous oxide-oxygen anaesthesia were assessed. In a preliminary study of three i.m. (2-, 4- and 8-mg) and six oral (1-,2-,2.5-,4-,5- and 8-mg) doses, the optimum dose was found to be 4 mg for patients with an average weight of 60 kg. This dose was studied in detail when given by all three routes and compared with the commercially available 2.5- and 5-mg tablets. Even when given i.v., there was a delay of 30-40 min in the onset of maximum sedative effect and drowsiness persisted for at least 4 h. Although the onset of action by i.m. injection was slightly faster than when the drug was given by mouth this advantage was more than offset by the high frequencies of pain at the site of injection and restlessness which persisted for 20-40 min. Oral lorazepam in doses of 2.5-5.0 mg was a reliable, effective sedative which could be recommended for routine preanaesthetic medication, provided rapid recovery was not essential. Its soporific effect was accompanied by an appreciable incidence of anterograde amnesia.", "contents": "Studies of drugs given before anaesthesia XXVI: lorazepam. Lorazepam has been studied as preanaesthetic medication given by mouth, i.m. and i.v. Sediation and side-effects and the incidence of anterograde amnesia in patients having a standard operation under methohexitone-nitrous oxide-oxygen anaesthesia were assessed. In a preliminary study of three i.m. (2-, 4- and 8-mg) and six oral (1-,2-,2.5-,4-,5- and 8-mg) doses, the optimum dose was found to be 4 mg for patients with an average weight of 60 kg. This dose was studied in detail when given by all three routes and compared with the commercially available 2.5- and 5-mg tablets. Even when given i.v., there was a delay of 30-40 min in the onset of maximum sedative effect and drowsiness persisted for at least 4 h. Although the onset of action by i.m. injection was slightly faster than when the drug was given by mouth this advantage was more than offset by the high frequencies of pain at the site of injection and restlessness which persisted for 20-40 min. Oral lorazepam in doses of 2.5-5.0 mg was a reliable, effective sedative which could be recommended for routine preanaesthetic medication, provided rapid recovery was not essential. Its soporific effect was accompanied by an appreciable incidence of anterograde amnesia."}
{"id": "PMID:21679", "title": "Substrate and substrate analogue binding properties of Renilla luciferase.", "content": "Luciferase from the anthozoan coelenterate Renilla reniformis catalyzes the oxidative decarboxylation of luciferin consuming 1 mol of O2 per mol of luciferin oxidized and producing 1 mol of CO2, 1 mol of oxyluciferin, and light (lambdaB, 480 nm) with a 5.5% quantum yield. In this work we have examined the binding characteristics of luciferin, luciferin analogues, and competitive inhibitors of the luciferin-luciferase reaction. The results show that luciferin binding and orientation in the single luciferin binding site of luciferase are highly specific for and dependent upon the three group substituents of the luciferin molecule while the imidazolone-pyrazine nucleus of luciferin is not directly involved in binding. Anaerobic luciferin binding promotes a rapid concentration-dependent aggregation of luciferase which results in irreversible inactivation of the enzyme. This aggregation phenomenon is not observed upon binding of oxyluciferin, luciferyl sulfate, or luciferin analogues in which the substituent at the 2 position of the imidazolone-pyrazine ring has been substantially altered.", "contents": "Substrate and substrate analogue binding properties of Renilla luciferase. Luciferase from the anthozoan coelenterate Renilla reniformis catalyzes the oxidative decarboxylation of luciferin consuming 1 mol of O2 per mol of luciferin oxidized and producing 1 mol of CO2, 1 mol of oxyluciferin, and light (lambdaB, 480 nm) with a 5.5% quantum yield. In this work we have examined the binding characteristics of luciferin, luciferin analogues, and competitive inhibitors of the luciferin-luciferase reaction. The results show that luciferin binding and orientation in the single luciferin binding site of luciferase are highly specific for and dependent upon the three group substituents of the luciferin molecule while the imidazolone-pyrazine nucleus of luciferin is not directly involved in binding. Anaerobic luciferin binding promotes a rapid concentration-dependent aggregation of luciferase which results in irreversible inactivation of the enzyme. This aggregation phenomenon is not observed upon binding of oxyluciferin, luciferyl sulfate, or luciferin analogues in which the substituent at the 2 position of the imidazolone-pyrazine ring has been substantially altered."}
{"id": "PMID:21680", "title": "Pyridoxamine-pyruvate transaminase. 1. Determination of the active site stoichiometry and the pH dependence of the dissociation constant for 5'-deoxypyridoxal.", "content": "Spectrophotometric titration of pyridoxamine-pyruvate transaminase (EC 2.6.1.30) with pyridoxal at pH 7.15 gives four equivalent binding sites per tetramer. The pH dependence of the equilibrium constant for the association of 5'-deoxypyridoxal with the active site lysine residue was determined spectrophotometrically. These dissociation constants increase with increasing pH over the range pH 7.5-9 and are correlated with the values obtained from fast reactions kinetics (Gilmer, P. J., and Kirsch, J. F. (1977), Biochemistry 16 (following paper in this issue)). In addition to this specific reaction at an active site lysine residue, a second slower reaction at non-active site residues is observable at pH values greater than 8. The pH dependencies of the association and dissociation rate constants for this slow reaction were studied over the pH range 8 to 9 after blocking the active site by NaBH4 reduction of the pyridoxal adduct. The enzyme is stabilized and markedly activated by potassium ion.", "contents": "Pyridoxamine-pyruvate transaminase. 1. Determination of the active site stoichiometry and the pH dependence of the dissociation constant for 5'-deoxypyridoxal. Spectrophotometric titration of pyridoxamine-pyruvate transaminase (EC 2.6.1.30) with pyridoxal at pH 7.15 gives four equivalent binding sites per tetramer. The pH dependence of the equilibrium constant for the association of 5'-deoxypyridoxal with the active site lysine residue was determined spectrophotometrically. These dissociation constants increase with increasing pH over the range pH 7.5-9 and are correlated with the values obtained from fast reactions kinetics (Gilmer, P. J., and Kirsch, J. F. (1977), Biochemistry 16 (following paper in this issue)). In addition to this specific reaction at an active site lysine residue, a second slower reaction at non-active site residues is observable at pH values greater than 8. The pH dependencies of the association and dissociation rate constants for this slow reaction were studied over the pH range 8 to 9 after blocking the active site by NaBH4 reduction of the pyridoxal adduct. The enzyme is stabilized and markedly activated by potassium ion."}
{"id": "PMID:21683", "title": "Isoelectric focus analysis of rat anti-phosphocholine antibodies.", "content": "Anti-phosphocholine (PC) antibodies in sera from four strains of rats were examined before and afterimmunization with either Streptococcus pneumoniae R36A, which contains PC as a cell wall component, or with PC-coupled keyhole limpet hemocyanin (PC-KLH). PC-specific protein was purified from pooled immune sera and shown by a combination of isoelectric focus (IEF) in acrylamide and crossed immunoelectrophoresis, as well as by molecular weight determination in NaDodSO4-acrylamide, to be immunoglobulin. An additional, small molecular weight, nonimmunoglobulin protein (pI = 7.1-7.3) was present in sera from normal and germ-free rats which had the ability to bind the C-carbohydrate of S. pneumoniae R36A, but without specificity for PC. The IEF profile of normal and immune sera showed marked sharing of bands of anti-PC antibody between individual rats as well as between strains. In addition, other anti-PC antibodies which focused between pH 8.5 and 9.5 were less regularly shared. The uniformity of IEF profile of the bulk of anti-PC antibodies in rats is most consistent with their being the products of germ line genes.", "contents": "Isoelectric focus analysis of rat anti-phosphocholine antibodies. Anti-phosphocholine (PC) antibodies in sera from four strains of rats were examined before and afterimmunization with either Streptococcus pneumoniae R36A, which contains PC as a cell wall component, or with PC-coupled keyhole limpet hemocyanin (PC-KLH). PC-specific protein was purified from pooled immune sera and shown by a combination of isoelectric focus (IEF) in acrylamide and crossed immunoelectrophoresis, as well as by molecular weight determination in NaDodSO4-acrylamide, to be immunoglobulin. An additional, small molecular weight, nonimmunoglobulin protein (pI = 7.1-7.3) was present in sera from normal and germ-free rats which had the ability to bind the C-carbohydrate of S. pneumoniae R36A, but without specificity for PC. The IEF profile of normal and immune sera showed marked sharing of bands of anti-PC antibody between individual rats as well as between strains. In addition, other anti-PC antibodies which focused between pH 8.5 and 9.5 were less regularly shared. The uniformity of IEF profile of the bulk of anti-PC antibodies in rats is most consistent with their being the products of germ line genes."}
{"id": "PMID:21684", "title": "Interaction of oligoribocytidylates with T7 DNA in neutral and acid media.", "content": "Oligoribocytidylates of chain length 4 to 12 were found to interact with native T7 DNA at neutral and slightly acid pH. The results suggest that binding occurred at deoxycytosine clusters which may be displaced by the oligomers at neutral pH, while a local triple-stranded structure would be formed at acid pH. Transcription of DNA-(Cp)n complexes by Escherichia coli RNA polymerase showed a decrease in level without affecting the specificity of the transcription, suggesting that oligocytidylate binding did not occur on the promoters.", "contents": "Interaction of oligoribocytidylates with T7 DNA in neutral and acid media. Oligoribocytidylates of chain length 4 to 12 were found to interact with native T7 DNA at neutral and slightly acid pH. The results suggest that binding occurred at deoxycytosine clusters which may be displaced by the oligomers at neutral pH, while a local triple-stranded structure would be formed at acid pH. Transcription of DNA-(Cp)n complexes by Escherichia coli RNA polymerase showed a decrease in level without affecting the specificity of the transcription, suggesting that oligocytidylate binding did not occur on the promoters."}
{"id": "PMID:21685", "title": "Rabbit liver transglutaminase: physical, chemical, and catalytic properties.", "content": "Transglutaminase (R-glutaminyl-peptide:amine alpha-glutamyl-yltransferase [EC 2.3.2.13]) has been purified to apparent homogeneity from extracts of rabbit liver. The enzyme is a single polypeptide chain of approximately 80 000 molecular weight containing one catalytic site per molecule. That the isolated enzyme is the rabbit counterpart of the well-characterized guinea pig liver transglutaminase is evidenced by the similarities in their amino acid compositions and in their enzymic activities toward several substrates, together with the fact that the isolated rabbit enzyme is immunologically distinct from both rabbit plasma and rabbit platelet blood coagulation factor XIII. A striking difference between the catalytic activities of the rabbit and guinea pig enzymes is the low activity of rabbit transglutaminase for hydroxylamine incorporation into benzyloxycarbonyl-L-glutaminylglycine, a reaction for which the guinea pig enzyme shows a high reactivity. This finding reveals the cause of error in an earlier report (Tyler, H.M., and Laki, K. (1967) Biochemistry 6, 3259) that rabbit liver contains little, if any, of the enzyme. Preparation of, and analytical data on, several glutamine-containing peptide derivatives used in this study are reported here.", "contents": "Rabbit liver transglutaminase: physical, chemical, and catalytic properties. Transglutaminase (R-glutaminyl-peptide:amine alpha-glutamyl-yltransferase [EC 2.3.2.13]) has been purified to apparent homogeneity from extracts of rabbit liver. The enzyme is a single polypeptide chain of approximately 80 000 molecular weight containing one catalytic site per molecule. That the isolated enzyme is the rabbit counterpart of the well-characterized guinea pig liver transglutaminase is evidenced by the similarities in their amino acid compositions and in their enzymic activities toward several substrates, together with the fact that the isolated rabbit enzyme is immunologically distinct from both rabbit plasma and rabbit platelet blood coagulation factor XIII. A striking difference between the catalytic activities of the rabbit and guinea pig enzymes is the low activity of rabbit transglutaminase for hydroxylamine incorporation into benzyloxycarbonyl-L-glutaminylglycine, a reaction for which the guinea pig enzyme shows a high reactivity. This finding reveals the cause of error in an earlier report (Tyler, H.M., and Laki, K. (1967) Biochemistry 6, 3259) that rabbit liver contains little, if any, of the enzyme. Preparation of, and analytical data on, several glutamine-containing peptide derivatives used in this study are reported here."}
{"id": "PMID:21687", "title": "Classification and localization of hemoglobin binding sites on the red blood cell membrane.", "content": "The binding of hemoglobin to the red cell membrane was characterized over a wide range of free hemoglobin concentrations by measurement of membrane bound and supernatant hemoglobin. Scatchard analysis of the binding data revealed two classes of sites: high affinity sites with a binding constant of 1 X 10(8) M-1 and 1.2 X 10(6) sites per cell, and a second, low affinity class of sites with a binding constant of 6 X 10(6)M-1 and 6 X 10(6) sites per cell. The low affinity sites are shown to be nonspecific and appear to be a result of the ghost preparation. The high affinity sites are shown to be specific to the inner surface of the red cell membrane. The competition of hemoglobin and glyceraldehyde-3-phosphate dehydrogenase suggests band III proteins as a potential binding site for hemoglobin.", "contents": "Classification and localization of hemoglobin binding sites on the red blood cell membrane. The binding of hemoglobin to the red cell membrane was characterized over a wide range of free hemoglobin concentrations by measurement of membrane bound and supernatant hemoglobin. Scatchard analysis of the binding data revealed two classes of sites: high affinity sites with a binding constant of 1 X 10(8) M-1 and 1.2 X 10(6) sites per cell, and a second, low affinity class of sites with a binding constant of 6 X 10(6)M-1 and 6 X 10(6) sites per cell. The low affinity sites are shown to be nonspecific and appear to be a result of the ghost preparation. The high affinity sites are shown to be specific to the inner surface of the red cell membrane. The competition of hemoglobin and glyceraldehyde-3-phosphate dehydrogenase suggests band III proteins as a potential binding site for hemoglobin."}
{"id": "PMID:21689", "title": "A change in the internal affinity of LK goat red-cell sodium pumps induced by high pH.", "content": "The K inhibition of ouabain-sensitive ATPase activity of LK goat red cell membranes is greatly reduced at high pH. This effect is reversible, and specific, since the apparent affinities for ATP, ouabain or external K do not alter. Anti-L-treated membranes show a similar alkali-induced affinity change, but have a lower pH optimum.", "contents": "A change in the internal affinity of LK goat red-cell sodium pumps induced by high pH. The K inhibition of ouabain-sensitive ATPase activity of LK goat red cell membranes is greatly reduced at high pH. This effect is reversible, and specific, since the apparent affinities for ATP, ouabain or external K do not alter. Anti-L-treated membranes show a similar alkali-induced affinity change, but have a lower pH optimum."}
{"id": "PMID:21690", "title": "Counter-transport mediated by the lactose permease of Escherichia coli.", "content": "When the two main energy yielding pathways, respiration and the membrane ATPase of Escherichia coli are poisoned, the lactose permease is unable to accomplish accumulative transport of thiogalactosides, but the efflux of preloaded substrate can be coupled to a transiently uphill transport of exogenous substrate. This transient uphill transport, called overshoot has been reexamined with the possibility of an obligate H+ cotransport in mind. Overshoot can be diminished but not suppressed by a proton-conducting uncoupler, carbonyl cyanide m chlorophenylhydrazone, (CCCP) and by a liposoluble cation, triphenyl-methyl phosphonium (TPMP+). The effect of other factors, such as temperature, amount of permease and pH were also explored. The overshoot was found to decrease with increasing pH, until at pH 8 it became negligible. This is in sharp contrast with the relatively flat pH dependence of uphill and downhill transport in unpoisoned cells. CCCP and TPMP+ had no inhibitory effect on the overshoot at pH 6 and below.", "contents": "Counter-transport mediated by the lactose permease of Escherichia coli. When the two main energy yielding pathways, respiration and the membrane ATPase of Escherichia coli are poisoned, the lactose permease is unable to accomplish accumulative transport of thiogalactosides, but the efflux of preloaded substrate can be coupled to a transiently uphill transport of exogenous substrate. This transient uphill transport, called overshoot has been reexamined with the possibility of an obligate H+ cotransport in mind. Overshoot can be diminished but not suppressed by a proton-conducting uncoupler, carbonyl cyanide m chlorophenylhydrazone, (CCCP) and by a liposoluble cation, triphenyl-methyl phosphonium (TPMP+). The effect of other factors, such as temperature, amount of permease and pH were also explored. The overshoot was found to decrease with increasing pH, until at pH 8 it became negligible. This is in sharp contrast with the relatively flat pH dependence of uphill and downhill transport in unpoisoned cells. CCCP and TPMP+ had no inhibitory effect on the overshoot at pH 6 and below."}
{"id": "PMID:21691", "title": "Fractionation of membrane vesicles. II. A method for separation of membrane vesicles bearing different enzymes by free-flow electrophoresis.", "content": "Free-flow electrophoresis was used to subfractionate membrane vesicles from calf thymocyte plasma membranes. The fractionation resulted in a separation of vesicle populations bearing four different enzymes: alkaline nitrophenyl-phosphatase (orthophosphoric-monoester phosphohydrolase (alkalin optimum) EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), (Mg2+ + Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and acyl-CoA:lysophosphatidylcholine acyltransferase (acyl-CoA:1-acylglycero-3-phosphocholine-O-acyltransferase, EC 2.3.1.23). The specific content of cholesterol and total phospholipid coincided with the distribution of membrane-bound protein. However, vesicles migrating towards the cathode had a higher molar ratio of cholesterol to phospholipid (0.75) compared to those migrating to the anode (0.55). Sodium dodecyl sulphate-gel electrophoresis of pooled vesicle fractions also demonstrates distinct differences in their protein pattern. Electron-micrographic thin sections show that the vesicle populations have a similar morphology and size distribution. These results are discussed in terms of heterogeneity of the original thymocytes, contamination with intracellular membranes and a heterogeneous structure of the plasma membrane.", "contents": "Fractionation of membrane vesicles. II. A method for separation of membrane vesicles bearing different enzymes by free-flow electrophoresis. Free-flow electrophoresis was used to subfractionate membrane vesicles from calf thymocyte plasma membranes. The fractionation resulted in a separation of vesicle populations bearing four different enzymes: alkaline nitrophenyl-phosphatase (orthophosphoric-monoester phosphohydrolase (alkalin optimum) EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), (Mg2+ + Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and acyl-CoA:lysophosphatidylcholine acyltransferase (acyl-CoA:1-acylglycero-3-phosphocholine-O-acyltransferase, EC 2.3.1.23). The specific content of cholesterol and total phospholipid coincided with the distribution of membrane-bound protein. However, vesicles migrating towards the cathode had a higher molar ratio of cholesterol to phospholipid (0.75) compared to those migrating to the anode (0.55). Sodium dodecyl sulphate-gel electrophoresis of pooled vesicle fractions also demonstrates distinct differences in their protein pattern. Electron-micrographic thin sections show that the vesicle populations have a similar morphology and size distribution. These results are discussed in terms of heterogeneity of the original thymocytes, contamination with intracellular membranes and a heterogeneous structure of the plasma membrane."}
{"id": "PMID:21692", "title": "Permeability of amino acids into liposomes.", "content": "1. A simple and rapid assay for the measurement of permeability of amino acids into liposome membrane was carried out by using the liposomes trapping D-amino acid oxidase (D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3) inside the membrane. 2. Permeability of amino acids into liposomes depended on the lipid composition of the membrane. Permeability of amino acids into phosphatidylcholine-cholesterol liposomes depended critically on temperature. 3. Permeability also depended on the structure of amino acids. The order of permeability was norvaline greater than isoleucine greater than leucine greater than phenylalanine greater than tryptophan greater than methionine greater than tyrosine, valine greater than threonine greater than serine greater than alanine greater than glycine.", "contents": "Permeability of amino acids into liposomes. 1. A simple and rapid assay for the measurement of permeability of amino acids into liposome membrane was carried out by using the liposomes trapping D-amino acid oxidase (D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3) inside the membrane. 2. Permeability of amino acids into liposomes depended on the lipid composition of the membrane. Permeability of amino acids into phosphatidylcholine-cholesterol liposomes depended critically on temperature. 3. Permeability also depended on the structure of amino acids. The order of permeability was norvaline greater than isoleucine greater than leucine greater than phenylalanine greater than tryptophan greater than methionine greater than tyrosine, valine greater than threonine greater than serine greater than alanine greater than glycine."}
{"id": "PMID:21694", "title": "Effects of pH on the properties of normal and 5-fluorouracil-containing tRNAs.", "content": "Transfer RNAs isolated from Escherichia coli B grown in the presence of 5-fluorouracil (FIUra) show variations in their aminoacylation levels when compared with normal samples. Some of these variations result from the more stringent aminoacylation reaction conditions required for FIUra-tRNAs. Increasing the reaction pH from 7 to 9 for example, generally causes a lowering of amino acid acceptance by the analog-containing tRNAs, while leaving control samples largely unchanged. This decreased activity appears to result primarily from fluorouracil ionization, which in turn disrupts intramolecular hydrogen bonding and promotes an overall increase in the molecular dimensions of FIUra-tRNAs at elevated pH values. Sensitivity to pH differes with the amino acid examined, with lysine showing dramatic changes and glutamine and proline being largely unaffected.", "contents": "Effects of pH on the properties of normal and 5-fluorouracil-containing tRNAs. Transfer RNAs isolated from Escherichia coli B grown in the presence of 5-fluorouracil (FIUra) show variations in their aminoacylation levels when compared with normal samples. Some of these variations result from the more stringent aminoacylation reaction conditions required for FIUra-tRNAs. Increasing the reaction pH from 7 to 9 for example, generally causes a lowering of amino acid acceptance by the analog-containing tRNAs, while leaving control samples largely unchanged. This decreased activity appears to result primarily from fluorouracil ionization, which in turn disrupts intramolecular hydrogen bonding and promotes an overall increase in the molecular dimensions of FIUra-tRNAs at elevated pH values. Sensitivity to pH differes with the amino acid examined, with lysine showing dramatic changes and glutamine and proline being largely unaffected."}
{"id": "PMID:21695", "title": "Properties of D(+)-lysopine dehydrogenase from crown gall tumour tissue.", "content": "D(+)-Lysopine dehydrogenase of an octopine-type Crown Gall tumour has been partially purified and a number of kinetic parameters have been determined. D(+)-Lysopine dehydrogenase catalyzes the reductive condensation of pyruvate and one of at least six different L-amino acids, as well as the reverse reactions, with preferential use of NADP(H) as a cofactor. The optimal pH for both reductive and oxidative reactions has been determined. At pH 6.8, L-lysine has of all the amino acids the lowest Km value, while at the same pH the highest V was found with L-arginine and L-histidine. The isoelectric point of D(+)-lysopine dehydrogenase is about 4.5.", "contents": "Properties of D(+)-lysopine dehydrogenase from crown gall tumour tissue. D(+)-Lysopine dehydrogenase of an octopine-type Crown Gall tumour has been partially purified and a number of kinetic parameters have been determined. D(+)-Lysopine dehydrogenase catalyzes the reductive condensation of pyruvate and one of at least six different L-amino acids, as well as the reverse reactions, with preferential use of NADP(H) as a cofactor. The optimal pH for both reductive and oxidative reactions has been determined. At pH 6.8, L-lysine has of all the amino acids the lowest Km value, while at the same pH the highest V was found with L-arginine and L-histidine. The isoelectric point of D(+)-lysopine dehydrogenase is about 4.5."}
{"id": "PMID:21696", "title": "Coordinate and non-coordinate accululation of aspartate transcarbamylase and dihydroorotase in synchronous Chlorella cells growing on different nitrogen sources.", "content": "Regulation of the levels of aspartate transcarbamylase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydro-orotate amidohydrolase, EC 3.5.2.3) was studied in synchronous cultures of the eucaryotic microorganism Chlorella. Analytical polyacrylamide gel electrophoresis and sucrose density-gradient centrifugation studies revealed that these cells contain a single aspartate transcarbamylase and a dihydroorotase with apparent molecular weights of 160 000 and 80 000, respectively. In synchronous cells cultured in nitrate medium, these two enzymes accumulated in single step-patterns over different periods of the cell cycle. In contrast, these enzymes accumulated in a coordinate manner throughout the cell cycle in ammonium medium. Experiments with inhibitors of protein and RNA synthesis indicated that dihydroorotase is stable in vivo and suggested that cell cycle changes in the turnover rate of aspartate transcarbamylase might determine whether or not these enzymes accumulate in a coordinate manner. Although uracil and uridine could be absorbed and metabolized by the cells, synthesis of these two enzymes could not be repressed by culturing synchronous cells in medium, containing high concentrations (29-40 mM) of uracil or uridine, for an entire cell cycle.", "contents": "Coordinate and non-coordinate accululation of aspartate transcarbamylase and dihydroorotase in synchronous Chlorella cells growing on different nitrogen sources. Regulation of the levels of aspartate transcarbamylase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) and dihydroorotase (L-5,6-dihydro-orotate amidohydrolase, EC 3.5.2.3) was studied in synchronous cultures of the eucaryotic microorganism Chlorella. Analytical polyacrylamide gel electrophoresis and sucrose density-gradient centrifugation studies revealed that these cells contain a single aspartate transcarbamylase and a dihydroorotase with apparent molecular weights of 160 000 and 80 000, respectively. In synchronous cells cultured in nitrate medium, these two enzymes accumulated in single step-patterns over different periods of the cell cycle. In contrast, these enzymes accumulated in a coordinate manner throughout the cell cycle in ammonium medium. Experiments with inhibitors of protein and RNA synthesis indicated that dihydroorotase is stable in vivo and suggested that cell cycle changes in the turnover rate of aspartate transcarbamylase might determine whether or not these enzymes accumulate in a coordinate manner. Although uracil and uridine could be absorbed and metabolized by the cells, synthesis of these two enzymes could not be repressed by culturing synchronous cells in medium, containing high concentrations (29-40 mM) of uracil or uridine, for an entire cell cycle."}
{"id": "PMID:21697", "title": "Characterization of the aspartate carbamoyltransferase fragment generated by protease action on the pyrimidine-3 gene product of Neurospora crassa.", "content": "The molecular weight of the fragment of aspartate carbamoyltransferase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) of Neurospora crassa following proteolysis was found to be 1.0-10(5) (aspartate carbamoyltransferase-L). It differs from the native form of the enzyme (aspartate carbamoyltransferase-N, 6.5-10(5)) in several respects. It has a lower V, has a much greater affinity (approx. 3-fold) for L-aspartate, and is strongly activated by glycine. Both forms of aspartate carbamyoltransferase have a pH optimum of approx. 9.5, and they exhibit similar affinities for carbamoyl phosphate.", "contents": "Characterization of the aspartate carbamoyltransferase fragment generated by protease action on the pyrimidine-3 gene product of Neurospora crassa. The molecular weight of the fragment of aspartate carbamoyltransferase (carbamoylphosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) of Neurospora crassa following proteolysis was found to be 1.0-10(5) (aspartate carbamoyltransferase-L). It differs from the native form of the enzyme (aspartate carbamoyltransferase-N, 6.5-10(5)) in several respects. It has a lower V, has a much greater affinity (approx. 3-fold) for L-aspartate, and is strongly activated by glycine. Both forms of aspartate carbamyoltransferase have a pH optimum of approx. 9.5, and they exhibit similar affinities for carbamoyl phosphate."}
{"id": "PMID:21698", "title": "Differential stabilities of soil enzymes. Assay and properties of phosphatase and arylsulphatase.", "content": "Methods have been refined for the assay of phosphatase and arylsulphatase activities in soil, based on the chromogenic p-nitrophenyl ester substrates. Basic assay conditions have been defined, and pH optima and kinetic parameters have been determined. The enzymes follow Michaelis-Menten kinetics; this conclusion is based on three methods of analysis of data determined over a wide range of substrate concentrations. The enzyme activities are very stable to storage of wet soil for up to 4 weeks at soil temperatures and above. For example, phosphatase had a half-life of approximately 2 weeks at 50 degrees C; arylsulphatase was rather less stable. Both enzymes retained 80% of activity after incubation with pronase for 1 week at 25 degrees C. On the basis of this work and studies on other soil enzymes, it is concluded that remarkable stability is a general feature of soil enzymes.", "contents": "Differential stabilities of soil enzymes. Assay and properties of phosphatase and arylsulphatase. Methods have been refined for the assay of phosphatase and arylsulphatase activities in soil, based on the chromogenic p-nitrophenyl ester substrates. Basic assay conditions have been defined, and pH optima and kinetic parameters have been determined. The enzymes follow Michaelis-Menten kinetics; this conclusion is based on three methods of analysis of data determined over a wide range of substrate concentrations. The enzyme activities are very stable to storage of wet soil for up to 4 weeks at soil temperatures and above. For example, phosphatase had a half-life of approximately 2 weeks at 50 degrees C; arylsulphatase was rather less stable. Both enzymes retained 80% of activity after incubation with pronase for 1 week at 25 degrees C. On the basis of this work and studies on other soil enzymes, it is concluded that remarkable stability is a general feature of soil enzymes."}
{"id": "PMID:21699", "title": "Purification of an acid proteinase from Aspergillus saitoi and determination of peptide bond specificity.", "content": "The specificity and mode of action of an acid proteinase (EC 3.4.23.6) from Aspergillus saitoi were investigated with oxidized B-chain of insulin, angiotensin II and bradykinin. Further purification of acid proteinase was performed with N,O-dibenzyloxycarbonyl-tyrosine hexamethylene-diamino-Sepharose 4B affinity chromatography and isoelectric focusing. The purified enzyme was free of any other proteolytic activity demonstrated in Asp. saitoi. Acid proteinase from Asp. saitoi hydrolyzed primarily two peptide bonds in the oxidized B-chain of insulin, the Leu(15)-Tyr(16) bond and the Phe(24)-Phe(25) bond. Additional cleavages of the bonds His(10)-Leu(11), Ala(14)-Leu(15) and Tyr(16)-Leu(17) were also noted. Primary splitting sites at Leu(15)-Tyr(16) and Phe(24-)-Phe(25) with acid proteinase from Asp. saitoi were identical with those reported in the work of cathepsin D (EC 3.4.23.5) from human erythrocyte. Hydrolysis of angiotensin II was observed at the Tyr(4)-Ile(5) bond. In conclusion, peptide bonds which have a hydrophobic amino acid such as phenylalanine, tyrosine, leucine and isoleucine in the P'1 position (as defined by Berger and Schechter, [29]) are preferentially cleaved by the trypsinogenactivating acid proteinase from Asp. saitoi.", "contents": "Purification of an acid proteinase from Aspergillus saitoi and determination of peptide bond specificity. The specificity and mode of action of an acid proteinase (EC 3.4.23.6) from Aspergillus saitoi were investigated with oxidized B-chain of insulin, angiotensin II and bradykinin. Further purification of acid proteinase was performed with N,O-dibenzyloxycarbonyl-tyrosine hexamethylene-diamino-Sepharose 4B affinity chromatography and isoelectric focusing. The purified enzyme was free of any other proteolytic activity demonstrated in Asp. saitoi. Acid proteinase from Asp. saitoi hydrolyzed primarily two peptide bonds in the oxidized B-chain of insulin, the Leu(15)-Tyr(16) bond and the Phe(24)-Phe(25) bond. Additional cleavages of the bonds His(10)-Leu(11), Ala(14)-Leu(15) and Tyr(16)-Leu(17) were also noted. Primary splitting sites at Leu(15)-Tyr(16) and Phe(24-)-Phe(25) with acid proteinase from Asp. saitoi were identical with those reported in the work of cathepsin D (EC 3.4.23.5) from human erythrocyte. Hydrolysis of angiotensin II was observed at the Tyr(4)-Ile(5) bond. In conclusion, peptide bonds which have a hydrophobic amino acid such as phenylalanine, tyrosine, leucine and isoleucine in the P'1 position (as defined by Berger and Schechter, [29]) are preferentially cleaved by the trypsinogenactivating acid proteinase from Asp. saitoi."}
{"id": "PMID:21700", "title": "Purification of the tyrosine inhibitable 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Schizosaccharomyces pombe.", "content": "A method is described for the purification of the tyrosine inhibitable isoenzyme 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate-lyase(pyruvate phosphorylating), EC 4.1.2.15) to homogeneity as judged by polyacrylamide gel electrophoresis.", "contents": "Purification of the tyrosine inhibitable 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Schizosaccharomyces pombe. A method is described for the purification of the tyrosine inhibitable isoenzyme 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate-lyase(pyruvate phosphorylating), EC 4.1.2.15) to homogeneity as judged by polyacrylamide gel electrophoresis."}
{"id": "PMID:21701", "title": "The effect of an NADPH-regenerating system on biphenyl metabolism in isolated rat hepatocytes.", "content": "Biphenyl 4-hydroxylation was studied in isolated rat hepatocytes. It was found that there was in inter-relationship between 4-hydroxylase activity and glucuronidase activity, removal of 4-hydroxybiphenyl by conjugation being necessary to stimulate a second phase of hydroxylation. Addition of an NADPH-regenerating system resulted in an initial depression of both processes, but later their activities were enhanced. This action could not be explained by the presence of non-viable cells.", "contents": "The effect of an NADPH-regenerating system on biphenyl metabolism in isolated rat hepatocytes. Biphenyl 4-hydroxylation was studied in isolated rat hepatocytes. It was found that there was in inter-relationship between 4-hydroxylase activity and glucuronidase activity, removal of 4-hydroxybiphenyl by conjugation being necessary to stimulate a second phase of hydroxylation. Addition of an NADPH-regenerating system resulted in an initial depression of both processes, but later their activities were enhanced. This action could not be explained by the presence of non-viable cells."}
{"id": "PMID:21702", "title": "Relationship between intramitochondrial citrate and the activity of carbamoyl-phosphate synthase (ammonia).", "content": "The possibility of control of the activity of carbamoyl-phosphate synthase (ammonia) (EC 2.7.2.5) in rat-liver mitochondria by variation in the intramitochondrial free Mg2+ concentration has been investigated. Carbamoyl-phosphate synthase activity was measured by coupling the formation of carbamoylphosphate to the synthesis of citrulline in a reaction mixture containing ammonia, bicarbonate, a source of ATP, and ornithine. The synthesis of citrulline was inhibited by lowering the concentration of intramitochondrial free Mg2+. This could be achieved not only by depleting the mitochondria of Mg2+ (by adding the ionophore A23187), but also by increasing the intramitochondrial concentration of citrate. Under various conditions an inverse relationship between the rate of citrulline synthesis and the magnitude of the intramitochondrial concentration of citrate was observed. Inhibition of citrulline synthesis by intramitochondrial citrate could be partly reversed by addition of Mg2+ in the presence of A23187. Possible implications of the regulation of carbamoyl-phosphate synthase (ammonia) activity by intramitochondrial citrate for nitrogen metabolism in the liver are discussed.", "contents": "Relationship between intramitochondrial citrate and the activity of carbamoyl-phosphate synthase (ammonia). The possibility of control of the activity of carbamoyl-phosphate synthase (ammonia) (EC 2.7.2.5) in rat-liver mitochondria by variation in the intramitochondrial free Mg2+ concentration has been investigated. Carbamoyl-phosphate synthase activity was measured by coupling the formation of carbamoylphosphate to the synthesis of citrulline in a reaction mixture containing ammonia, bicarbonate, a source of ATP, and ornithine. The synthesis of citrulline was inhibited by lowering the concentration of intramitochondrial free Mg2+. This could be achieved not only by depleting the mitochondria of Mg2+ (by adding the ionophore A23187), but also by increasing the intramitochondrial concentration of citrate. Under various conditions an inverse relationship between the rate of citrulline synthesis and the magnitude of the intramitochondrial concentration of citrate was observed. Inhibition of citrulline synthesis by intramitochondrial citrate could be partly reversed by addition of Mg2+ in the presence of A23187. Possible implications of the regulation of carbamoyl-phosphate synthase (ammonia) activity by intramitochondrial citrate for nitrogen metabolism in the liver are discussed."}
{"id": "PMID:21704", "title": "Lectins in the hemolymph of Japanese horseshoe crab, tachypleus tridentatus.", "content": "The hemolymph of the Japanese horseshoe crab, Tachypleus tridentatus contains lectins which agglutinate mammalian erythrocytes. Affinity chromatographic purification of the lectins using bovine submaxillary gland mucin-conjugated Sepharose resulted in the separation of the lectins into four fractions; one major and three minor lectins. Protein subunits revealed by polyacrylamide gel electrophoresis and the immunoprecipitin line of these lectins against antiserum to crude lectins were unique to each fraction. The activities of all the lectins were optimal at pH values between 6 and 8, and were destroyed by heating at 60 degrees C. Calcium chloride augumented the activities of three lectins, but the major lectin was not influenced by the salt. Bovine erythrocytes were not agglutinated by any of the lectins and comparative agglutination titers for other erythrocytes from various sources were different among these lectins. The activities of all the lectins were inhibited by N-acetylamino sugars. They were more effectively inhibited by glycoproteins which contain sialic acid.", "contents": "Lectins in the hemolymph of Japanese horseshoe crab, tachypleus tridentatus. The hemolymph of the Japanese horseshoe crab, Tachypleus tridentatus contains lectins which agglutinate mammalian erythrocytes. Affinity chromatographic purification of the lectins using bovine submaxillary gland mucin-conjugated Sepharose resulted in the separation of the lectins into four fractions; one major and three minor lectins. Protein subunits revealed by polyacrylamide gel electrophoresis and the immunoprecipitin line of these lectins against antiserum to crude lectins were unique to each fraction. The activities of all the lectins were optimal at pH values between 6 and 8, and were destroyed by heating at 60 degrees C. Calcium chloride augumented the activities of three lectins, but the major lectin was not influenced by the salt. Bovine erythrocytes were not agglutinated by any of the lectins and comparative agglutination titers for other erythrocytes from various sources were different among these lectins. The activities of all the lectins were inhibited by N-acetylamino sugars. They were more effectively inhibited by glycoproteins which contain sialic acid."}
{"id": "PMID:21705", "title": "Coordination-chemistry study of polypeptides. III. protonation-deprotonation equilibrium study of synthetic alphaH -corticotropin1-32. Data on the pH-dependent conformation of corticotropin.", "content": "By potentiometric equilibrium measurements and the computer evaluation of experimental data, the protonation equilibrium constants of four fragments of corticotropin (ACTH), ACTH1-32. ACTH1-28, ACTH1-14 and ACTH1-4, were determined and assigned to the corresponding functional groups. From the dependence of the protonation constants on the length of the peptide chain, it was established which functional groups participate in the formation of intramolecular hydrogen-bonds in aqueous solutions at various pH. These results indicated a pH-dependent conformation of the molecule.", "contents": "Coordination-chemistry study of polypeptides. III. protonation-deprotonation equilibrium study of synthetic alphaH -corticotropin1-32. Data on the pH-dependent conformation of corticotropin. By potentiometric equilibrium measurements and the computer evaluation of experimental data, the protonation equilibrium constants of four fragments of corticotropin (ACTH), ACTH1-32. ACTH1-28, ACTH1-14 and ACTH1-4, were determined and assigned to the corresponding functional groups. From the dependence of the protonation constants on the length of the peptide chain, it was established which functional groups participate in the formation of intramolecular hydrogen-bonds in aqueous solutions at various pH. These results indicated a pH-dependent conformation of the molecule."}
{"id": "PMID:21706", "title": "[Studies of basic proteins of 60S- and 40S-subunits of pea seed ribosomes by two-dimensional polyacrylamide gel electrophoresis].", "content": "Basic proteins of 60S- and 40S-subunits of pea seed ribosomes were studied by two-dimensional electrophoresis in polyacrylamide gel (PAAG) with subsequent electrophoresis of separated proteins in the gels containing sodium dodecyl sulfate. The proteins under study were found to be electrophoretically heterogenous and showed considerable variations in the staining by amido black and a specific distribution between the two subunits. 47 protein components were detected in the protein preparations of the 60S subunit: 18--as intensively stained, 12--as moderately stained and 17--as weakly stained spots. Presumably, the 60S subunit does not contain proteins whose molecular weights are over 60.000 or below 14.000. Two proteins have mol. weight over 50.000; other proteins have mol. weights varying between 15.000 and 30.000. 32 proteins components were revealed in the protein preparations of the 40S subunit: 15--as intensively coloured, 8--as moderately coloured and 9--as weakly coloured spots. The 40S subunit does not contain proteins whose molecular weights are over 33.000 and below 10.000. Three proteins have mol. weights over 30.000, the other proteins have mol. weights within the interval of 15.000--30.000. The amount of basic proteins in the 80S plant ribosomes is, in all probability, higher as compared to that in animal ribosomes, and this is due to the 60S subunit.", "contents": "[Studies of basic proteins of 60S- and 40S-subunits of pea seed ribosomes by two-dimensional polyacrylamide gel electrophoresis]. Basic proteins of 60S- and 40S-subunits of pea seed ribosomes were studied by two-dimensional electrophoresis in polyacrylamide gel (PAAG) with subsequent electrophoresis of separated proteins in the gels containing sodium dodecyl sulfate. The proteins under study were found to be electrophoretically heterogenous and showed considerable variations in the staining by amido black and a specific distribution between the two subunits. 47 protein components were detected in the protein preparations of the 60S subunit: 18--as intensively stained, 12--as moderately stained and 17--as weakly stained spots. Presumably, the 60S subunit does not contain proteins whose molecular weights are over 60.000 or below 14.000. Two proteins have mol. weight over 50.000; other proteins have mol. weights varying between 15.000 and 30.000. 32 proteins components were revealed in the protein preparations of the 40S subunit: 15--as intensively coloured, 8--as moderately coloured and 9--as weakly coloured spots. The 40S subunit does not contain proteins whose molecular weights are over 33.000 and below 10.000. Three proteins have mol. weights over 30.000, the other proteins have mol. weights within the interval of 15.000--30.000. The amount of basic proteins in the 80S plant ribosomes is, in all probability, higher as compared to that in animal ribosomes, and this is due to the 60S subunit."}
{"id": "PMID:21709", "title": "Recent developments in the biochemistry of globoid and metachromatic leucodystrophies.", "content": "Galactosylceramides and their sulphates are the main constituents of myelin sheath of the nerve cell. Two genetically determined disorders are the results of an inability to enzymatically hydrolyse these glycolipids. Thus the deficiency of galactosylceramide beta-galactosidase results in globoid cell leucodystrophy and the reduced activity of enzyme, arylsulphatase A is responsible for the disease Metachromatic leucodystrophy. Both these disorders are fatal and are characterized by marked demyelination and severe mental retardation. Since homognenous enzyme preparations of galactosylceramide beta-galactosidase and arylsulphatase A are now available, a possibility of enzyme replacement therapy in globoid and metachromatic leucodystrophies has been discussed.", "contents": "Recent developments in the biochemistry of globoid and metachromatic leucodystrophies. Galactosylceramides and their sulphates are the main constituents of myelin sheath of the nerve cell. Two genetically determined disorders are the results of an inability to enzymatically hydrolyse these glycolipids. Thus the deficiency of galactosylceramide beta-galactosidase results in globoid cell leucodystrophy and the reduced activity of enzyme, arylsulphatase A is responsible for the disease Metachromatic leucodystrophy. Both these disorders are fatal and are characterized by marked demyelination and severe mental retardation. Since homognenous enzyme preparations of galactosylceramide beta-galactosidase and arylsulphatase A are now available, a possibility of enzyme replacement therapy in globoid and metachromatic leucodystrophies has been discussed."}
{"id": "PMID:21710", "title": "In-vitro and in-vivo properties of canine blood mononuclear leukocytes separated by discontinuous albumin density gradient centrifugation.", "content": "Dogs were given 1 200 R whole body x-irradiation and transfused with frozen and thawed mononuclear leukocytes from a DLA identical, MLC negative donor dog. These leukocytes had been obtained from the peripheral blood by means of leukapheresis, using the IBM experimental cell separator after injection of 15 mg/kg body weight of dextran sulphate to increase the yield of CFUc upon collection. The segregation of leukocytes by means of the discontinuous albumin gradient centrifugation method resulted in a fraction 2 that contained a very high proportion of CFUc, and in other fractions 3 and 4 with a high proportion of lymphocytes with few CFUc. The dog receiving fraction-2 cells showed a rapid bone marrow recovery (permanent) and displayed no signs of gvh-reaction. The dogs receiving cells of fraction 3 or 4 died of gvh-reaction within 25 days. The dog receiving fraction 4 cells showed little hemopoietic recovery, but a marked lymph node hyperplasia of plasma cells.", "contents": "In-vitro and in-vivo properties of canine blood mononuclear leukocytes separated by discontinuous albumin density gradient centrifugation. Dogs were given 1 200 R whole body x-irradiation and transfused with frozen and thawed mononuclear leukocytes from a DLA identical, MLC negative donor dog. These leukocytes had been obtained from the peripheral blood by means of leukapheresis, using the IBM experimental cell separator after injection of 15 mg/kg body weight of dextran sulphate to increase the yield of CFUc upon collection. The segregation of leukocytes by means of the discontinuous albumin gradient centrifugation method resulted in a fraction 2 that contained a very high proportion of CFUc, and in other fractions 3 and 4 with a high proportion of lymphocytes with few CFUc. The dog receiving fraction-2 cells showed a rapid bone marrow recovery (permanent) and displayed no signs of gvh-reaction. The dogs receiving cells of fraction 3 or 4 died of gvh-reaction within 25 days. The dog receiving fraction 4 cells showed little hemopoietic recovery, but a marked lymph node hyperplasia of plasma cells."}
{"id": "PMID:21711", "title": "Local anesthetics. Effect of pH on use-dependent block of sodium channels in frog muscle.", "content": "Sodium currents were studied under voltage clamp in the presence of neutral, amine, and quaternary local anesthetic compounds. Use-dependent block was observed as a cumulative depression of INa seen with repetitive depolarizing test pulses applied at frequencies of 2-10s-1. With quaternary QX-314, the time constant of use dependence was long, and with neutral benzocaine, very short. With lidocaine and procaine, increasing external pH (pHo) changed the time constant from long to short, but alterations of internal pH have no effect. Inactivation in Na channels was measured by the influence of prepulses on peak INa during test pulses. Single-stimulus inactivation curves were shifted more with lidocaine at high pHo than at low pHo, but inactivation curves measured during pulse trains with any of the drugs and at any pHo were strongly shifted. All measurements show that the drug-receptor reaction was slow for amine drugs at low pHo, as for quaternary drugs at any pHo, and fast for amine drugs at high pHo, as for neutral drugs at any pHo. The major effect of low pHo on amine drugs was to reduce the concentration of drugs in the fiber and to protonate drug molecules on the receptor, thus trapping them in the blocking position for a longer time. Direct effects of pH on the receptor seemed minimal.", "contents": "Local anesthetics. Effect of pH on use-dependent block of sodium channels in frog muscle. Sodium currents were studied under voltage clamp in the presence of neutral, amine, and quaternary local anesthetic compounds. Use-dependent block was observed as a cumulative depression of INa seen with repetitive depolarizing test pulses applied at frequencies of 2-10s-1. With quaternary QX-314, the time constant of use dependence was long, and with neutral benzocaine, very short. With lidocaine and procaine, increasing external pH (pHo) changed the time constant from long to short, but alterations of internal pH have no effect. Inactivation in Na channels was measured by the influence of prepulses on peak INa during test pulses. Single-stimulus inactivation curves were shifted more with lidocaine at high pHo than at low pHo, but inactivation curves measured during pulse trains with any of the drugs and at any pHo were strongly shifted. All measurements show that the drug-receptor reaction was slow for amine drugs at low pHo, as for quaternary drugs at any pHo, and fast for amine drugs at high pHo, as for neutral drugs at any pHo. The major effect of low pHo on amine drugs was to reduce the concentration of drugs in the fiber and to protonate drug molecules on the receptor, thus trapping them in the blocking position for a longer time. Direct effects of pH on the receptor seemed minimal."}
{"id": "PMID:21713", "title": "The effect of acid pH on the growth kinetics of Trichoderma viride.", "content": "Batch cultures of Trichoderma viride have been carried out in a 10 liter stirred fermenter a controlled pH values of 2.5, 2.7, 3.0, and 4.0 and without pH control at a temperature of 28 degrees C. Cell and glucose concentrations and dissolved oxygen values are reported. The yield coefficient was found to be constant at 0.40 kg cells/kg glucose and the maximum specific growth rate was linearly correlated with the hydrogen ion concentration.", "contents": "The effect of acid pH on the growth kinetics of Trichoderma viride. Batch cultures of Trichoderma viride have been carried out in a 10 liter stirred fermenter a controlled pH values of 2.5, 2.7, 3.0, and 4.0 and without pH control at a temperature of 28 degrees C. Cell and glucose concentrations and dissolved oxygen values are reported. The yield coefficient was found to be constant at 0.40 kg cells/kg glucose and the maximum specific growth rate was linearly correlated with the hydrogen ion concentration."}
{"id": "PMID:21714", "title": "Preparation and properties of immobilized papain and lipase.", "content": "Papain and lipase were immobilized on derivatized Sepharose 4-B. The activated agarose had a binding capacity of 1.2 micronmol amino groups/ml packed agarose or 17 mg proteins/g dry agarose. The immobilized enzyme preparations were tested for the effects of pH of assay, temperature of assay, and substrate concentrations. The effect of 6M urea on the activity of papain was also determined. Soluble forms of the enzymes were used for comparison. Immobilization of the enzymes resulted in slightly different pH and temperature optima for activities. For immobilized papain Km(app) was similar to the one observed with soluble papain. Immobilization of lipase, however, cause a decrease in Km values. The immobilized enzyme preparations were stable when stored at 4 degrees C and pH 7.5 for periods up to eight months. The soluble enzymes lost their activity within 96 hr under similar storage conditions. Immobilized papain did not lose any activity after treatment with 6M urea for 270 min, whereas soluble papain lost 81% of its activity after the urea treatment, indicating that the immobilization of papain imparted structural and conformational stability to this enzyme.", "contents": "Preparation and properties of immobilized papain and lipase. Papain and lipase were immobilized on derivatized Sepharose 4-B. The activated agarose had a binding capacity of 1.2 micronmol amino groups/ml packed agarose or 17 mg proteins/g dry agarose. The immobilized enzyme preparations were tested for the effects of pH of assay, temperature of assay, and substrate concentrations. The effect of 6M urea on the activity of papain was also determined. Soluble forms of the enzymes were used for comparison. Immobilization of the enzymes resulted in slightly different pH and temperature optima for activities. For immobilized papain Km(app) was similar to the one observed with soluble papain. Immobilization of lipase, however, cause a decrease in Km values. The immobilized enzyme preparations were stable when stored at 4 degrees C and pH 7.5 for periods up to eight months. The soluble enzymes lost their activity within 96 hr under similar storage conditions. Immobilized papain did not lose any activity after treatment with 6M urea for 270 min, whereas soluble papain lost 81% of its activity after the urea treatment, indicating that the immobilization of papain imparted structural and conformational stability to this enzyme."}
{"id": "PMID:21715", "title": "Development of hematopoietic spleen colonies in nonirradiated genetically normal mice.", "content": "The question as to whether prior irradiation or injection of cytotoxic drugs is essential for the development of spleen colonies was examined in genetically normal mice. Mixtures of lymph node and bone marrow cells from C57BL mice were injected into (C57BL X CBA-T6T6) F1 hybrid mice without pretreatment. Hematopoietic nodules were observed in the spleens of F1 hybrid mice killed 18 days after injection. The average number of nodules increased linearly with increased numbers of injected bone marrow cells. Hematopoietic stem cells (CFU-S) and dividing cells in the nodules were shown to be of C57BL origin. Histologic examination showed that erythroid cell colonies predominated over granulocytic cell colonies. These results suggest that any kind of treatment that causes the depletion of CFU-S in the spleen of hosts would provide a suitable environment for the production of colonies by transplanted CFU-S.", "contents": "Development of hematopoietic spleen colonies in nonirradiated genetically normal mice. The question as to whether prior irradiation or injection of cytotoxic drugs is essential for the development of spleen colonies was examined in genetically normal mice. Mixtures of lymph node and bone marrow cells from C57BL mice were injected into (C57BL X CBA-T6T6) F1 hybrid mice without pretreatment. Hematopoietic nodules were observed in the spleens of F1 hybrid mice killed 18 days after injection. The average number of nodules increased linearly with increased numbers of injected bone marrow cells. Hematopoietic stem cells (CFU-S) and dividing cells in the nodules were shown to be of C57BL origin. Histologic examination showed that erythroid cell colonies predominated over granulocytic cell colonies. These results suggest that any kind of treatment that causes the depletion of CFU-S in the spleen of hosts would provide a suitable environment for the production of colonies by transplanted CFU-S."}
{"id": "PMID:21720", "title": "Further studies of sulphasalazine metabolism in the treatment of ulcerative colitis.", "content": "Sixty-four outpatients with ulcerative colitis receiving maintenance treatment with sulphasalazine were studied to relate disease activity to serum concentrations of sulphapyridine. Of 43 patients in remission, 32 had serum sulphapyridine levels over 20 microgram/ml. Ten of the 21 patients with active disease were for various reasons taking inadequate doses of sulphasalazine, as indicated by low serum sulphapyridine levels, and of the remaining 11 patients, who had serum levels over 20 microgram/ml, nine had faecal stasis proximal to active distal colitis and went into remission when treated with hydrophilic colloid or bran and an unchanged sulphasalazine dosage. This suggests that to be effective the metabolites of sulphasalazine must be delivered in the faeces to the lumen of the diseased distal segment of the colon. High serum concentrations of sulphapyridine produce side effects; therefore slow acetylators of sulphapyridine need lower doses of sulphasalazine. Estimations of serum sulphapyridine concentrations, as well as identifying the patient's acetylation phenotype, can also be useful in assessing his compliance with treatment.", "contents": "Further studies of sulphasalazine metabolism in the treatment of ulcerative colitis. Sixty-four outpatients with ulcerative colitis receiving maintenance treatment with sulphasalazine were studied to relate disease activity to serum concentrations of sulphapyridine. Of 43 patients in remission, 32 had serum sulphapyridine levels over 20 microgram/ml. Ten of the 21 patients with active disease were for various reasons taking inadequate doses of sulphasalazine, as indicated by low serum sulphapyridine levels, and of the remaining 11 patients, who had serum levels over 20 microgram/ml, nine had faecal stasis proximal to active distal colitis and went into remission when treated with hydrophilic colloid or bran and an unchanged sulphasalazine dosage. This suggests that to be effective the metabolites of sulphasalazine must be delivered in the faeces to the lumen of the diseased distal segment of the colon. High serum concentrations of sulphapyridine produce side effects; therefore slow acetylators of sulphapyridine need lower doses of sulphasalazine. Estimations of serum sulphapyridine concentrations, as well as identifying the patient's acetylation phenotype, can also be useful in assessing his compliance with treatment."}
{"id": "PMID:21726", "title": "Quinonoid dihydropterin reductase from beef liver.", "content": "Quinonoid dihydropterin reductase has been purified from beef liver. This enzyme has been shown to be indistinguishable from the reductase of sheep liver in molecular weight, subunit composition, and terminal residues. Both beef and sheep liver reductases possess acyl isoleucine as the N-terminal residue. Use of improved isolation techniques, including general ligand affinity chromatography, has yielded enzyme preparations of much higher specific activity than previously reported. Affinity chromatography experiments also suggest that the enzymic reaction proceeds by a compulsory ordered mechanism.", "contents": "Quinonoid dihydropterin reductase from beef liver. Quinonoid dihydropterin reductase has been purified from beef liver. This enzyme has been shown to be indistinguishable from the reductase of sheep liver in molecular weight, subunit composition, and terminal residues. Both beef and sheep liver reductases possess acyl isoleucine as the N-terminal residue. Use of improved isolation techniques, including general ligand affinity chromatography, has yielded enzyme preparations of much higher specific activity than previously reported. Affinity chromatography experiments also suggest that the enzymic reaction proceeds by a compulsory ordered mechanism."}
{"id": "PMID:21727", "title": "Isolation and properties of a glycerophosphate acylating fraction in the fat body of Schistocerca gregaria (Forsk\u00e4l).", "content": "An acyl-CoA-L-alpha-glycerophosphate acyltransferase system has been found in the fat body of the locust Schistocerca gregaria (Forsk\u00e4l). After homogenization and differential centrifugation the enzyme system has been localized in two distinct particulate fractions. In both fractions phosphatidic acid was the main reaction product. The 10 000 g -30 000 g particulate fraction was further studied. The enzyme system is very sensitive to pH and Mg2+ concentration. An apparent Km of 0.3-0.5 mM for glycerophosphate was measured. The substrate concentration curve for palmitoyl-CoA is influenced by the protein concentration in the assay medium. This effect would partly explain the non-lineariy of the acylation reactions with respect to enzyme concentration. These observations are correlated with physiological phenomena.", "contents": "Isolation and properties of a glycerophosphate acylating fraction in the fat body of Schistocerca gregaria (Forsk\u00e4l). An acyl-CoA-L-alpha-glycerophosphate acyltransferase system has been found in the fat body of the locust Schistocerca gregaria (Forsk\u00e4l). After homogenization and differential centrifugation the enzyme system has been localized in two distinct particulate fractions. In both fractions phosphatidic acid was the main reaction product. The 10 000 g -30 000 g particulate fraction was further studied. The enzyme system is very sensitive to pH and Mg2+ concentration. An apparent Km of 0.3-0.5 mM for glycerophosphate was measured. The substrate concentration curve for palmitoyl-CoA is influenced by the protein concentration in the assay medium. This effect would partly explain the non-lineariy of the acylation reactions with respect to enzyme concentration. These observations are correlated with physiological phenomena."}
{"id": "PMID:21728", "title": "Heterogeneity of alkaline ribonuclease in the mouse and Ehrlich ascites cells.", "content": "The specific activity of alkaline RNase II was l00 to 1800 times higher in mouse pancreas than in mouse liver, serum, ascites fluid, and Ehrlich ascites cell grown intraperitoneally. Ehrlich ascites cells grown in cell culture medium had a much lower alkaline RNase II activity than cells grown intraperitoneally. Chromatography on CM-52 cellulose of acid- and heat-treated preparations showned a considerable heterogeneity of the mouse enzymes. Depending on the source of the extract, two to six forms fo alkaline RNase were eluted. Pancreatic extract contained two RNase forms. These also seemed to be present as minor components in preparations from other sources except Ehrlich ascites cells grown in vitro. Ehrlich ascites cells grown in vivo contained forms of the RNase which were not present in other extracts. Possible reasons for this heterogeneity were investigated. In addition to their stability to acid and heat the different RNase forms were similar in that they were much more active at alkaline pH than at acidic pH, they did not require divalent metal ions for activity, and they degraded RNA 'endonucleolytically.' Also, native DNA, denatured DNA, and poly A were poor substrates compared with RNA. Some differences seemed to exist, however, with respect to their abilities to degrade poly U and poly C and their sensitivities to the endogenous RNase inhibitor.", "contents": "Heterogeneity of alkaline ribonuclease in the mouse and Ehrlich ascites cells. The specific activity of alkaline RNase II was l00 to 1800 times higher in mouse pancreas than in mouse liver, serum, ascites fluid, and Ehrlich ascites cell grown intraperitoneally. Ehrlich ascites cells grown in cell culture medium had a much lower alkaline RNase II activity than cells grown intraperitoneally. Chromatography on CM-52 cellulose of acid- and heat-treated preparations showned a considerable heterogeneity of the mouse enzymes. Depending on the source of the extract, two to six forms fo alkaline RNase were eluted. Pancreatic extract contained two RNase forms. These also seemed to be present as minor components in preparations from other sources except Ehrlich ascites cells grown in vitro. Ehrlich ascites cells grown in vivo contained forms of the RNase which were not present in other extracts. Possible reasons for this heterogeneity were investigated. In addition to their stability to acid and heat the different RNase forms were similar in that they were much more active at alkaline pH than at acidic pH, they did not require divalent metal ions for activity, and they degraded RNA 'endonucleolytically.' Also, native DNA, denatured DNA, and poly A were poor substrates compared with RNA. Some differences seemed to exist, however, with respect to their abilities to degrade poly U and poly C and their sensitivities to the endogenous RNase inhibitor."}
{"id": "PMID:21730", "title": "An analysis of the action of lanthanum on aortic tissue from normotensive and spontaneously hypertensive rats.", "content": "Significant tension development resulting from the administration of lanthanum salts (La3+) to isolated aorta tissues was observed in preparations from the spontaneously hypertensive rat (SHR) but not in preparation from age-matched normotensive Wistar rats (NWR). The response to La3+ was significantly greater in tissues maintained in bicarbonate-buffered Krebs than observed in bicarbonate and phosphate-free HEPES-buffered Krebs. At least part of the LA3+ response in the bicarbonate- and phosphate-buffered solutions was due to a pH shift and could be mimicked by raising the extracellular hydrogen ion [H+] concentration. However, a direct action of La3+ on excitation-contraction coupling could be observed in HEPES-buffered solutions where the addition of La3+ also resulted in tension development but no significant pH change; this action of La3+ was found to be resistant to inhibition by maintenance in a Ca2+-free medium and (or) D-600 pretreatment suggesting an intracellular action for La3+. The paradoxical response to both H+ and La3+ in the SHR aorta suggests that the muscle membrane may be more permeable to these ions and, in addition, suggests that the membrane and (or) intracellular calcium stores in this tissue may also be more labile than those in the normotensive controls.", "contents": "An analysis of the action of lanthanum on aortic tissue from normotensive and spontaneously hypertensive rats. Significant tension development resulting from the administration of lanthanum salts (La3+) to isolated aorta tissues was observed in preparations from the spontaneously hypertensive rat (SHR) but not in preparation from age-matched normotensive Wistar rats (NWR). The response to La3+ was significantly greater in tissues maintained in bicarbonate-buffered Krebs than observed in bicarbonate and phosphate-free HEPES-buffered Krebs. At least part of the LA3+ response in the bicarbonate- and phosphate-buffered solutions was due to a pH shift and could be mimicked by raising the extracellular hydrogen ion [H+] concentration. However, a direct action of La3+ on excitation-contraction coupling could be observed in HEPES-buffered solutions where the addition of La3+ also resulted in tension development but no significant pH change; this action of La3+ was found to be resistant to inhibition by maintenance in a Ca2+-free medium and (or) D-600 pretreatment suggesting an intracellular action for La3+. The paradoxical response to both H+ and La3+ in the SHR aorta suggests that the muscle membrane may be more permeable to these ions and, in addition, suggests that the membrane and (or) intracellular calcium stores in this tissue may also be more labile than those in the normotensive controls."}
{"id": "PMID:21732", "title": "Role of transmitters in mediating hypothalamic control of electrolyte excretion.", "content": "Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway.", "contents": "Role of transmitters in mediating hypothalamic control of electrolyte excretion. Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway."}
{"id": "PMID:21733", "title": "Bile-salt-dependent and independent choleresis induced by bucolome in the rat.", "content": "Choleresis induced by bucolome (BC) (1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydropyrimidine) was studied in male Wistar rats. [14C]Erythritol and mannitol clearance studies indicated this choleresis to be of canalicular origin. In 1-h continuous bile collection studies, immediately after the interruption of enterohepatic circulation (acute interruption), both bile flow and bile salt excretion rates were significantly increased in rats administered BC. However, the bile salt excretion rate fell rather rapidly in BC-administered rats, while the bile flow rate was fairly constant during this 1-h period. Thus, unlike the situation in control rats, bile flow rate was not significantly correlated with the bile salt excretion rate in BC-administered rats. In rats that had an external bile fistula open for 16-20 h (chronic interruption of enterohepatic circulation) the bile flow rate was also significantly increased by BC administration, while the bile salt excretion rate was not changed after BC administration. It is suggested that BC induced bile-salt-independent choleresis in both experimental rat groups (acute and chronic interruption of enterohepatic circulation). In addition, BC appeared to increase the bile-salt-dependent fraction of bile in rats with acute interruption of enterohepatic circulation, possibly by mobilizing the bile salt pooled in the intestinal content and (or) intestinal wall.", "contents": "Bile-salt-dependent and independent choleresis induced by bucolome in the rat. Choleresis induced by bucolome (BC) (1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydropyrimidine) was studied in male Wistar rats. [14C]Erythritol and mannitol clearance studies indicated this choleresis to be of canalicular origin. In 1-h continuous bile collection studies, immediately after the interruption of enterohepatic circulation (acute interruption), both bile flow and bile salt excretion rates were significantly increased in rats administered BC. However, the bile salt excretion rate fell rather rapidly in BC-administered rats, while the bile flow rate was fairly constant during this 1-h period. Thus, unlike the situation in control rats, bile flow rate was not significantly correlated with the bile salt excretion rate in BC-administered rats. In rats that had an external bile fistula open for 16-20 h (chronic interruption of enterohepatic circulation) the bile flow rate was also significantly increased by BC administration, while the bile salt excretion rate was not changed after BC administration. It is suggested that BC induced bile-salt-independent choleresis in both experimental rat groups (acute and chronic interruption of enterohepatic circulation). In addition, BC appeared to increase the bile-salt-dependent fraction of bile in rats with acute interruption of enterohepatic circulation, possibly by mobilizing the bile salt pooled in the intestinal content and (or) intestinal wall."}
{"id": "PMID:21735", "title": "Regulation of pyruvate kinases from Fusarium oxysporum.", "content": "Two types of pyruvate kinases were found in Fusarium oxysporum. One type (inducible) was present mainly during the early stages of growth on glucose or sucrose and displayed Michaelis-Menten kinetics with respect to phosphoenolpyruvate and adenosine diphosphate. The major type (constitutive) was present under all conditions of growth and displayed in the absence of potassium ions, a sigmoidal substrate saturation curve when phosphoenolpyruvate was used as the variable substrate. In the presence of potassium ions the saturation curve for phosphoenolpyruvate exhibits a plateau at half-maximal velocity. The effects of various metabolites on the activity of the inducible and constitutive kinases were also studied. Fructose-1,6-diphosphate, cyclic AMP, acetyl CoA, tryptophan, and phenylalanine had no effect on the activity of the enzymes. Citrate was a potent inhibitor of the constitutive pyruvate kinase activity and increased the sigmoidicity of the saturation curve for phosphoenolpyruvic acid. In the presence of K+, the bimodal plot observed in the absence of citrate gradually changed to a hyperbolic shape as the concentration of citric acid was increased. In the presence of K+ and ADP as the variable substrate citric acid converted the hyperbolic plot to a sigmoidal one. Citrate had no effect on the inducible enzyme.", "contents": "Regulation of pyruvate kinases from Fusarium oxysporum. Two types of pyruvate kinases were found in Fusarium oxysporum. One type (inducible) was present mainly during the early stages of growth on glucose or sucrose and displayed Michaelis-Menten kinetics with respect to phosphoenolpyruvate and adenosine diphosphate. The major type (constitutive) was present under all conditions of growth and displayed in the absence of potassium ions, a sigmoidal substrate saturation curve when phosphoenolpyruvate was used as the variable substrate. In the presence of potassium ions the saturation curve for phosphoenolpyruvate exhibits a plateau at half-maximal velocity. The effects of various metabolites on the activity of the inducible and constitutive kinases were also studied. Fructose-1,6-diphosphate, cyclic AMP, acetyl CoA, tryptophan, and phenylalanine had no effect on the activity of the enzymes. Citrate was a potent inhibitor of the constitutive pyruvate kinase activity and increased the sigmoidicity of the saturation curve for phosphoenolpyruvic acid. In the presence of K+, the bimodal plot observed in the absence of citrate gradually changed to a hyperbolic shape as the concentration of citric acid was increased. In the presence of K+ and ADP as the variable substrate citric acid converted the hyperbolic plot to a sigmoidal one. Citrate had no effect on the inducible enzyme."}
{"id": "PMID:21736", "title": "The effect of different nitrogen sources on pigment production and sporulation of Monascus species in submerged, shaken culture.", "content": "Thirty-nine strains from the genus Monascus were cultivated aerobically to study the relation between nitrogen nutrition and sporulation and pigment production. The effects of yeast extract, nitrate, ammonium, and ammonium nitrate have been compared. During cultivation the pHs of the different media are not the same, resulting in the formation of different coloured pigments. When the source of nitrogen is yeast extract or nitrate the pH is around 6.5 and red pigments are formed, whereas with ammonium or ammonium nitrate the pH is around 2.5 and the pigments are orange. It is proposed that only the orange pigments, monascorubrin and rubropunctatin, are produced biosynthetically and that the other pigments are formed from these by chemical transformations depending on the cultural conditions. The presence of organic nitrogen is optimal for growth and unfavourable for pigment production. Reduced growth and best pigment formation occurs with the three other nitrogen sources. Nitrate stimulates conidiation and sexual reproduction, while ammonium is inhibitory. Pigment production is better when conidiation is reduced. A mechanism is proposed for the control of sporulation and pigment production.", "contents": "The effect of different nitrogen sources on pigment production and sporulation of Monascus species in submerged, shaken culture. Thirty-nine strains from the genus Monascus were cultivated aerobically to study the relation between nitrogen nutrition and sporulation and pigment production. The effects of yeast extract, nitrate, ammonium, and ammonium nitrate have been compared. During cultivation the pHs of the different media are not the same, resulting in the formation of different coloured pigments. When the source of nitrogen is yeast extract or nitrate the pH is around 6.5 and red pigments are formed, whereas with ammonium or ammonium nitrate the pH is around 2.5 and the pigments are orange. It is proposed that only the orange pigments, monascorubrin and rubropunctatin, are produced biosynthetically and that the other pigments are formed from these by chemical transformations depending on the cultural conditions. The presence of organic nitrogen is optimal for growth and unfavourable for pigment production. Reduced growth and best pigment formation occurs with the three other nitrogen sources. Nitrate stimulates conidiation and sexual reproduction, while ammonium is inhibitory. Pigment production is better when conidiation is reduced. A mechanism is proposed for the control of sporulation and pigment production."}
{"id": "PMID:21737", "title": "Physiological and biochemical studies on senescing tap root nodules of soybeans.", "content": "Senescence of soybean (Glycine max L. Merr.) tap root nodules was investigated by comparing changes in various physiological and biochemical activities with changes in capacity to fix nitrogen. Field-grown Beeson  and Calland varieties of soybeans of various ages were sources of tap root nodules. With both varieties, the number of tap root nodules per plant remained constant between 56 and 86 days after planting but fresh weight, dry weight, and mass of tap root nodules increased duing this period. Nitrogen (C2H2)fixation by attached tap root nodules was maximum on a fresh weight, dry weight, or nitrogen basis about 56 days after planting for either variety. Metabolic activities of bacteroids as measured by carbon dioxide evolution from glucose and succinate did not appear to vary among nodules of different ages. There was also no indication of mobilization or deposition or deposition of iron, molybdenum, calcium, zinc, and nitrate in aging tap root nodules. Nitrate levels in the aerial portion of the plants decreased significantly after the initial decline in acetylene reduction. Nicotinamide deamidase activity in the cytosol and in extracts of bacteroids did not change significantly as tap root nodules aged. However, significant and consistent changes were observed in initial pH values of nodule breis and the initial decline occurred before (Calland) or concurrently (Beeson) with the initial decline of nitrogen fixation.", "contents": "Physiological and biochemical studies on senescing tap root nodules of soybeans. Senescence of soybean (Glycine max L. Merr.) tap root nodules was investigated by comparing changes in various physiological and biochemical activities with changes in capacity to fix nitrogen. Field-grown Beeson  and Calland varieties of soybeans of various ages were sources of tap root nodules. With both varieties, the number of tap root nodules per plant remained constant between 56 and 86 days after planting but fresh weight, dry weight, and mass of tap root nodules increased duing this period. Nitrogen (C2H2)fixation by attached tap root nodules was maximum on a fresh weight, dry weight, or nitrogen basis about 56 days after planting for either variety. Metabolic activities of bacteroids as measured by carbon dioxide evolution from glucose and succinate did not appear to vary among nodules of different ages. There was also no indication of mobilization or deposition or deposition of iron, molybdenum, calcium, zinc, and nitrate in aging tap root nodules. Nitrate levels in the aerial portion of the plants decreased significantly after the initial decline in acetylene reduction. Nicotinamide deamidase activity in the cytosol and in extracts of bacteroids did not change significantly as tap root nodules aged. However, significant and consistent changes were observed in initial pH values of nodule breis and the initial decline occurred before (Calland) or concurrently (Beeson) with the initial decline of nitrogen fixation."}
{"id": "PMID:21738", "title": "Influence of acetohydroxamic acid on experimental Corynebacterium renale pyelonephritis.", "content": "The role of Corynebacterium renale urease in the establishment of pyelonephritis was studied by the oral administration of acetohydroxamic acid (AHA), a urease inhibitor, to experimentally infected rats. The bacteria were introduced by surgical insertion of a zinc disc containing 1 X 10(6) colony-forming units of C-renale into the urinary bladder whereas sterile discs were implanted in the bladders of the control animals. Daily administration of AHA via the drinking water did not halt the development of pyelonephritis. Larger doses, given by gavage, did accomplish this goal; that is, the pH of the urine was lowered, the number of colony-forming units of C. renale in the kidney was reduced drastically, and pyelonephritic lesions were observed in the kidney by light-microscopic examination. All experimental rats developed cystitis in varying degrees of severity. About 70% of the intact AHA given by gavage was excreted in the urine 24 h after administration of this compound. Rats implanted with a urease-negative mutant of C. renale displayed no signs of pyelonephritis but did develop cystitis.", "contents": "Influence of acetohydroxamic acid on experimental Corynebacterium renale pyelonephritis. The role of Corynebacterium renale urease in the establishment of pyelonephritis was studied by the oral administration of acetohydroxamic acid (AHA), a urease inhibitor, to experimentally infected rats. The bacteria were introduced by surgical insertion of a zinc disc containing 1 X 10(6) colony-forming units of C-renale into the urinary bladder whereas sterile discs were implanted in the bladders of the control animals. Daily administration of AHA via the drinking water did not halt the development of pyelonephritis. Larger doses, given by gavage, did accomplish this goal; that is, the pH of the urine was lowered, the number of colony-forming units of C. renale in the kidney was reduced drastically, and pyelonephritic lesions were observed in the kidney by light-microscopic examination. All experimental rats developed cystitis in varying degrees of severity. About 70% of the intact AHA given by gavage was excreted in the urine 24 h after administration of this compound. Rats implanted with a urease-negative mutant of C. renale displayed no signs of pyelonephritis but did develop cystitis."}
{"id": "PMID:21739", "title": "Metabolism of mandelic acid by Neurospora crassa.", "content": "Preliminary studies on the metabolism of manelic acid by Neurospora crassa reveal the operation of a pathway for its degradation which involves benzoyl formic acid, benzaldehyde, benzoic acid, 4-hydroxybenzoic acid, and protocatechuic acid as the intermediates. This pathway is different from the followed by bacterial systems and is the same as that observed in Aspergillus niger.", "contents": "Metabolism of mandelic acid by Neurospora crassa. Preliminary studies on the metabolism of manelic acid by Neurospora crassa reveal the operation of a pathway for its degradation which involves benzoyl formic acid, benzaldehyde, benzoic acid, 4-hydroxybenzoic acid, and protocatechuic acid as the intermediates. This pathway is different from the followed by bacterial systems and is the same as that observed in Aspergillus niger."}
{"id": "PMID:21742", "title": "The identification of individuals at high risk for large bowel cancer: an overview.", "content": "Attempts to identify individuals with increased susceptibility to colon cancer before clinical manifestations of disease, have recently been made. Early stages of abnormal growth of colonic epithelial cells, and related factors that may contribute to the development of colonic neoplasia have been shown. Based on the identification of early findings, programs to prevent the evolution of malignancy in individuals at increased risk are under consideration at the present time.", "contents": "The identification of individuals at high risk for large bowel cancer: an overview. Attempts to identify individuals with increased susceptibility to colon cancer before clinical manifestations of disease, have recently been made. Early stages of abnormal growth of colonic epithelial cells, and related factors that may contribute to the development of colonic neoplasia have been shown. Based on the identification of early findings, programs to prevent the evolution of malignancy in individuals at increased risk are under consideration at the present time."}
{"id": "PMID:21743", "title": "Activation of the guanylate cyclase-guanosine 3'5' monophosphate system of colonic mucosa by n-methyl-n'-nitro-n-nitrosoguanidine.", "content": "The effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the guanylate cyclase (GC)-guanosine 3'5' monophosphate (cGMP) system of rat colonic mucosa were studied. MNNG (1 mM) increased colonic mucosal cGMP from 1.8 +/- 0.2 to 22.5 +/- 2.7 pmol/mg protein in 5 minutes. Increases in response to MNNG occurred in the presence or absence of extracellular Ca2+, whereas the two-fold increase in mucosal cGMP mediated by carbamylcholine was abolished by exclusion of Ca2+. Although GC activity of mucosal homogenates was found predominantly (90%) in the 100,000 g particulate fraction, the effects of MNNG on mucosal cGMP correlated with stimulation of 100,000 g soluble GC by this agonist. MNNG increased soluble GC 13-fold over the corresponding basal with 4 mM Mn2+, and 48-fold with 4 mM Mg2+ as the sole available divalent cation. Compared with unstimulated GC, the MNNG-activated soluble enzyme was less dependent upon Mn2+ availability and effectively utilized Mg2+ as metal co-factor. N-ethylmaleimide, a sulfhydryl group alkylator, inhibited MNNG stimulation of GC and cGMP. Thus, expression of these MNNG actions may involve drug interaction with tissue thiol groups. Prior incubation of MNNG with thiol antioxidants or ascorbate also suppressed MNNG stimulation of GC, possibly through direct drug reactions involving nucleophilic and electrophilic reactants. The ability of MNNG to stimulate the colonic mucosal GC-cGMP system could be linked to its carcinogenic action.", "contents": "Activation of the guanylate cyclase-guanosine 3'5' monophosphate system of colonic mucosa by n-methyl-n'-nitro-n-nitrosoguanidine. The effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the guanylate cyclase (GC)-guanosine 3'5' monophosphate (cGMP) system of rat colonic mucosa were studied. MNNG (1 mM) increased colonic mucosal cGMP from 1.8 +/- 0.2 to 22.5 +/- 2.7 pmol/mg protein in 5 minutes. Increases in response to MNNG occurred in the presence or absence of extracellular Ca2+, whereas the two-fold increase in mucosal cGMP mediated by carbamylcholine was abolished by exclusion of Ca2+. Although GC activity of mucosal homogenates was found predominantly (90%) in the 100,000 g particulate fraction, the effects of MNNG on mucosal cGMP correlated with stimulation of 100,000 g soluble GC by this agonist. MNNG increased soluble GC 13-fold over the corresponding basal with 4 mM Mn2+, and 48-fold with 4 mM Mg2+ as the sole available divalent cation. Compared with unstimulated GC, the MNNG-activated soluble enzyme was less dependent upon Mn2+ availability and effectively utilized Mg2+ as metal co-factor. N-ethylmaleimide, a sulfhydryl group alkylator, inhibited MNNG stimulation of GC and cGMP. Thus, expression of these MNNG actions may involve drug interaction with tissue thiol groups. Prior incubation of MNNG with thiol antioxidants or ascorbate also suppressed MNNG stimulation of GC, possibly through direct drug reactions involving nucleophilic and electrophilic reactants. The ability of MNNG to stimulate the colonic mucosal GC-cGMP system could be linked to its carcinogenic action."}
{"id": "PMID:21744", "title": "Phospholipases A1 and A2 in subcellular fractions and plasma membranes of Krebs II ascites cells.", "content": "A method is described for the localization and characterization of phospholipases A1 and A2 (EC3.1.1.4) in Krebs II ascites cells, particularly in the plasma membranes. Cells were lysed with a Dounce homogenizer in an isotonic sucrose medium. Plasma membranes sediment with mitochondria and lysosomes during subcellular fractionation and are finally isolated on a continuous sucrose gradient. The membranes are localized at two levels in the gradient, at densities of 1.06 and 1.15, in which 5'-nucleotidase (EC 3.1.3.5) activity exhibits a 9- and 21-fold purification, respectively. Total contamination by endoplasmic reticulum, lysosomes, and mitochondria is 17 percent for the low-density membrane fraction and 25 percent for the high-density fraction. The phospholipases A present in Krebs II cells are active at pH 4.0 and pH 7.5. At the 2 pH values, they have A1 and A2 specificities. The intracellular distribution of acidic forms is comparable to that of acid phosphatase (EC 3.1.3.1), while neutral forms are localized like lactate dehydrogenase (EC 1.1.1.27). A small proportion of neutral phospholipase A2 has the same repartition on the sucrose gradient as nicotinamide adenine dinucleotide diaphorase (EF 1.6.4.3), an endoplasmic reticulum marker, and as 5'-nucleotidase, a plasma membrane marker.", "contents": "Phospholipases A1 and A2 in subcellular fractions and plasma membranes of Krebs II ascites cells. A method is described for the localization and characterization of phospholipases A1 and A2 (EC3.1.1.4) in Krebs II ascites cells, particularly in the plasma membranes. Cells were lysed with a Dounce homogenizer in an isotonic sucrose medium. Plasma membranes sediment with mitochondria and lysosomes during subcellular fractionation and are finally isolated on a continuous sucrose gradient. The membranes are localized at two levels in the gradient, at densities of 1.06 and 1.15, in which 5'-nucleotidase (EC 3.1.3.5) activity exhibits a 9- and 21-fold purification, respectively. Total contamination by endoplasmic reticulum, lysosomes, and mitochondria is 17 percent for the low-density membrane fraction and 25 percent for the high-density fraction. The phospholipases A present in Krebs II cells are active at pH 4.0 and pH 7.5. At the 2 pH values, they have A1 and A2 specificities. The intracellular distribution of acidic forms is comparable to that of acid phosphatase (EC 3.1.3.1), while neutral forms are localized like lactate dehydrogenase (EC 1.1.1.27). A small proportion of neutral phospholipase A2 has the same repartition on the sucrose gradient as nicotinamide adenine dinucleotide diaphorase (EF 1.6.4.3), an endoplasmic reticulum marker, and as 5'-nucleotidase, a plasma membrane marker."}
{"id": "PMID:21745", "title": "Selective tumor DNA synthesis inhibition: in vivo prodrug activation by an exogenous enzyme.", "content": "Using the combination of alpha-L-arabinofuranosidase from Aspergillus niger with beta-peltatin A-alpha-L-arabinofuranoside, the selective effect of a new cancer of chemotherapy method based on a pH-dependent activation of cancerostatic prodrugs by exogenous enzymes was studied. In comparative experiments the selectivity of prodrug activation was measured by 3H-thymidine incorporation in tumor and normal tissues of CBA mice inoculated im with the transplantable mammary carcinoma, MA-21224. The results show that this special type of carrier principle may lead to a higher degree of selectivity than the usual direct application of cancerostatic drugs.", "contents": "Selective tumor DNA synthesis inhibition: in vivo prodrug activation by an exogenous enzyme. Using the combination of alpha-L-arabinofuranosidase from Aspergillus niger with beta-peltatin A-alpha-L-arabinofuranoside, the selective effect of a new cancer of chemotherapy method based on a pH-dependent activation of cancerostatic prodrugs by exogenous enzymes was studied. In comparative experiments the selectivity of prodrug activation was measured by 3H-thymidine incorporation in tumor and normal tissues of CBA mice inoculated im with the transplantable mammary carcinoma, MA-21224. The results show that this special type of carrier principle may lead to a higher degree of selectivity than the usual direct application of cancerostatic drugs."}
{"id": "PMID:21746", "title": "Evidence for new catecholamines or related amino acids in some invertebrate sensory neurons.", "content": "In certain sensory neurons of many different invertebrate species, including the sea anemones. Metridium senile and Tealia felina and the crustacean Artemia salina, fluorophores are formed during the course of the fluorescent histochemical technique of Falck-Hillarp. The presumed catecholamine nature of the neuronal fluorogenic compound was investigated by microspectrofluorometry, and the spectral characteristics of the fluorescence in the taxonomically different species was found to be very similar (excitation maximum at 375 nm with a smaller peak or shoulder at 330 nm and sometimes a shoulder in the spectrum at 410 nm; emission maximum at 475 nm). The emission maximum coincides with that of the catecholamines and DOPA (475 nm). The excitation maximum (375 nm) directly after formaldehyde treatment, however- differs from that of the catecholamines and DOPA (410 nm), but is similar to the excitation maximum displayed by these catechol derivatives at acid pH. The spectral characteristics of the fluorophore in the sensory cells might therefore theoretically be explained by an acid pH in the cells. This means improbable, however, and it is suggested that the phenomenon is due to the presence of unknown catechol derivatives. Analyses of the pH-dependent spectral changes indicate that the presumed catechol derivative in Tealia felina is beta-hydroxylated, whereas that in Artemia salina is not.", "contents": "Evidence for new catecholamines or related amino acids in some invertebrate sensory neurons. In certain sensory neurons of many different invertebrate species, including the sea anemones. Metridium senile and Tealia felina and the crustacean Artemia salina, fluorophores are formed during the course of the fluorescent histochemical technique of Falck-Hillarp. The presumed catecholamine nature of the neuronal fluorogenic compound was investigated by microspectrofluorometry, and the spectral characteristics of the fluorescence in the taxonomically different species was found to be very similar (excitation maximum at 375 nm with a smaller peak or shoulder at 330 nm and sometimes a shoulder in the spectrum at 410 nm; emission maximum at 475 nm). The emission maximum coincides with that of the catecholamines and DOPA (475 nm). The excitation maximum (375 nm) directly after formaldehyde treatment, however- differs from that of the catecholamines and DOPA (410 nm), but is similar to the excitation maximum displayed by these catechol derivatives at acid pH. The spectral characteristics of the fluorophore in the sensory cells might therefore theoretically be explained by an acid pH in the cells. This means improbable, however, and it is suggested that the phenomenon is due to the presence of unknown catechol derivatives. Analyses of the pH-dependent spectral changes indicate that the presumed catechol derivative in Tealia felina is beta-hydroxylated, whereas that in Artemia salina is not."}
{"id": "PMID:21748", "title": "The induction of sister chromatid exchanges by cyclophosphamide in the presence of differently induced microsomal fractions of rat liver.", "content": "The induction of sister chromatid exchanges can be monitored by a test that incorporates the factor of metabolic activation in a simple manner. The results with cyclophosphamide show that in this test the induction of the metabolizing enzymes of the rat liver homogenates used is very important. 3-Methylcholanthrene induces little if any extra conversion of cyclophosphamide to SCE-inducing metabolites, compared with no induction. Aroclor 1254 and phenobarbital however, were very good inducers. The difference found between the liver homogenates concerning SCE induction corresponded with the differences in cyclophosphamide metabolism, which was measured as the decrease in NADPH induced by cyclophosphamide.", "contents": "The induction of sister chromatid exchanges by cyclophosphamide in the presence of differently induced microsomal fractions of rat liver. The induction of sister chromatid exchanges can be monitored by a test that incorporates the factor of metabolic activation in a simple manner. The results with cyclophosphamide show that in this test the induction of the metabolizing enzymes of the rat liver homogenates used is very important. 3-Methylcholanthrene induces little if any extra conversion of cyclophosphamide to SCE-inducing metabolites, compared with no induction. Aroclor 1254 and phenobarbital however, were very good inducers. The difference found between the liver homogenates concerning SCE induction corresponded with the differences in cyclophosphamide metabolism, which was measured as the decrease in NADPH induced by cyclophosphamide."}
{"id": "PMID:21754", "title": "[A gas chromatographic study of the composition of neutral and amino sugars in two neuraminidases, of bacterial and viral origin].", "content": "The neutral and aminosugar composition has been determined by gas-liquid chromatography for two neuraminidases, either bacterial, from Streptococcus pneumoniae, or viral, from Myxovirus influenzae A/Hong Kong/1/68.", "contents": "[A gas chromatographic study of the composition of neutral and amino sugars in two neuraminidases, of bacterial and viral origin]. The neutral and aminosugar composition has been determined by gas-liquid chromatography for two neuraminidases, either bacterial, from Streptococcus pneumoniae, or viral, from Myxovirus influenzae A/Hong Kong/1/68."}
{"id": "PMID:21755", "title": "[Action of toxins isolated from scorpion and sea anemone venoms on ileum isolated from reserpine-treated guinea pigs].", "content": "We have shown that the ileum isolated from a reserpinized guinea Pig does respond to toxin II obtained from Scorpion venom but does not react to Anemonia sulcata toxin. We conclude that if Acetylcholine is the neurotransmitter inducing pharmacological activity of Scorpion toxin it is serotonin which triggers activity of Anemonia sulcata toxin in ileum of a normal guinea Pig.", "contents": "[Action of toxins isolated from scorpion and sea anemone venoms on ileum isolated from reserpine-treated guinea pigs]. We have shown that the ileum isolated from a reserpinized guinea Pig does respond to toxin II obtained from Scorpion venom but does not react to Anemonia sulcata toxin. We conclude that if Acetylcholine is the neurotransmitter inducing pharmacological activity of Scorpion toxin it is serotonin which triggers activity of Anemonia sulcata toxin in ileum of a normal guinea Pig."}
{"id": "PMID:21756", "title": "Lysosomal and ATP changes after renal-stalk clamping in rats. I. Protective action of Trasylol.", "content": "The action of Trasylol on the lysosomal and ATP changes after renal-stalk clamping in rats was examined. It was found that, in the presence of an effective Trasylol concentration, a distinct stabilization of the lysosomal membrane can be detected after 30 min of renal-stalk clamping. It was also found that there is only an indirect relationship between lysosomal changes and ATP metabolism under the action of Trasylol. The more rapid regeneration of the ATP is a result of the better microcirculation. The results confirm the earlier belief that Trasylol acts primarily on the lysosomal membrane.", "contents": "Lysosomal and ATP changes after renal-stalk clamping in rats. I. Protective action of Trasylol. The action of Trasylol on the lysosomal and ATP changes after renal-stalk clamping in rats was examined. It was found that, in the presence of an effective Trasylol concentration, a distinct stabilization of the lysosomal membrane can be detected after 30 min of renal-stalk clamping. It was also found that there is only an indirect relationship between lysosomal changes and ATP metabolism under the action of Trasylol. The more rapid regeneration of the ATP is a result of the better microcirculation. The results confirm the earlier belief that Trasylol acts primarily on the lysosomal membrane."}
{"id": "PMID:21757", "title": "Humoral factors in shock causing bradycardia and myocardial depression.", "content": "Hypovolemic shock was maintained for 6 hours in dogs in which the heart was hemodynamically protected by a biological model described earlier. Blood of these dogs was exchanged with that of healthy dogs in which myocardial tension and heart rate were continuously monitored. It was found that rate and force of decline in the recipient dog in a fashion similar to the drop in the animal in shock. If, however, the pH of the infused blood was raised to normal, the bradycardia in the recipient dog was prevented but the myocardial depression was not abolished. Administration of aprotinin alone did not prevent the bradycardia or depression of contractility, whereas correction of the pH and treatment with aprotinin not only prevented the decline in both but led also to a transient increase in myocardial tension of the recipient animal. The results seem to indicate that 1) in shock myocardial depression and cardiac slowing are induced by humoral factors transferable by blood to a normal animal, 2) acidity caused the bradycardia but not drop of tension, 3) aprotinin prevents the depression of contractility only in a normal pH medium, and 4) aprotinin may prevent the action of a preformed myocardial depressant factor rather than inhibit its formation.", "contents": "Humoral factors in shock causing bradycardia and myocardial depression. Hypovolemic shock was maintained for 6 hours in dogs in which the heart was hemodynamically protected by a biological model described earlier. Blood of these dogs was exchanged with that of healthy dogs in which myocardial tension and heart rate were continuously monitored. It was found that rate and force of decline in the recipient dog in a fashion similar to the drop in the animal in shock. If, however, the pH of the infused blood was raised to normal, the bradycardia in the recipient dog was prevented but the myocardial depression was not abolished. Administration of aprotinin alone did not prevent the bradycardia or depression of contractility, whereas correction of the pH and treatment with aprotinin not only prevented the decline in both but led also to a transient increase in myocardial tension of the recipient animal. The results seem to indicate that 1) in shock myocardial depression and cardiac slowing are induced by humoral factors transferable by blood to a normal animal, 2) acidity caused the bradycardia but not drop of tension, 3) aprotinin prevents the depression of contractility only in a normal pH medium, and 4) aprotinin may prevent the action of a preformed myocardial depressant factor rather than inhibit its formation."}
{"id": "PMID:21758", "title": "A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster.", "content": "The development of heart failure in the cardiomyopathic hamster is associated with a decrease in norepinephrine stores and parallel increases in cardiac sympathetic tone and tyrosine hydroxylase activity. Despite the increase in tyrosine hydroxylase, cardiac norepinephrine synthesis does not increase in heart failure. In this study, we have shown that an accumulation of cardiac dopamine accompanies the decline of cardiac norepinephrine. The abnormal content of norepinephrine and of dopamine in the decompensating hamster heart is restored to normal by peripheral ganglionic blockade. The acute increase in cardiac sympathetic tone induced by immobilization stress in control hamsters mimics the alterations in cardiac catecholamine distribution found in heart failure. Other investigators have demonstrated similar alterations in the catecholamine content of the rat submaxillary gland and adrenal medulla following an increase in sympathetic input to these organs. We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. There is evidence that this shift which results in an accumulation of dopamine in the noradrenergic nerve terminals of the heart is a general manifestaion of augmented sympathetic nerve traffic rather than a peculiarity of hamster cardiomyopathy.", "contents": "A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster. The development of heart failure in the cardiomyopathic hamster is associated with a decrease in norepinephrine stores and parallel increases in cardiac sympathetic tone and tyrosine hydroxylase activity. Despite the increase in tyrosine hydroxylase, cardiac norepinephrine synthesis does not increase in heart failure. In this study, we have shown that an accumulation of cardiac dopamine accompanies the decline of cardiac norepinephrine. The abnormal content of norepinephrine and of dopamine in the decompensating hamster heart is restored to normal by peripheral ganglionic blockade. The acute increase in cardiac sympathetic tone induced by immobilization stress in control hamsters mimics the alterations in cardiac catecholamine distribution found in heart failure. Other investigators have demonstrated similar alterations in the catecholamine content of the rat submaxillary gland and adrenal medulla following an increase in sympathetic input to these organs. We conclude that the increase in cardiac sympathetic tone in the late stages of hamster cardiomyopathy appears to lead to a shift in the rate-limiting step for norepinephrine synthesis from the hydroxylation of tyrosine to the hydroxylation of dopamine. There is evidence that this shift which results in an accumulation of dopamine in the noradrenergic nerve terminals of the heart is a general manifestaion of augmented sympathetic nerve traffic rather than a peculiarity of hamster cardiomyopathy."}
{"id": "PMID:21760", "title": "Natural history and classification of occlusive thromboaortopathy (Takayasu's disease).", "content": "Fifty-four Japanese patients with occlusive thromboaortopathy (OTAP), including four males, were classified according to evidence of complications attributed to OTAP at the time when the diagnosis was established: Group I, uncomplicated OTAP with or without the involvement of the pulmonary artery. Group II, mono-complicated OTAP: presence of a single complication together with uncomplicated OTAP. Group II was subdivided according to severity into group IIa - mild or moderate form, and group IIb - severe form. Group III, multi-complicated OTAP with two or more complications as well as uncomplicated OTAP. The five-year survival rate after established diagnosis was 83.1%. Seven patients died of OTAP within five years, but all had belonged to group IIb or III.", "contents": "Natural history and classification of occlusive thromboaortopathy (Takayasu's disease). Fifty-four Japanese patients with occlusive thromboaortopathy (OTAP), including four males, were classified according to evidence of complications attributed to OTAP at the time when the diagnosis was established: Group I, uncomplicated OTAP with or without the involvement of the pulmonary artery. Group II, mono-complicated OTAP: presence of a single complication together with uncomplicated OTAP. Group II was subdivided according to severity into group IIa - mild or moderate form, and group IIb - severe form. Group III, multi-complicated OTAP with two or more complications as well as uncomplicated OTAP. The five-year survival rate after established diagnosis was 83.1%. Seven patients died of OTAP within five years, but all had belonged to group IIb or III."}
{"id": "PMID:21761", "title": "Effectiveness of an outpatient urine screening program.", "content": "We evaluated the effectiveness of a routine outpatient urinalysis screening program on a sample population of 2600 patients. The 189 abnormal urine results found in 182 patients were followed up by study of any new clinical and laboratory investigations or therapeutic modifications initiated on the basis of any abnormal test result. The urinalysis screening program appeared to have significant bearing on diagnosis or treatment in only 13 patients. Abnormalities found in 150 of the 182 patients were either not noted or no further positive action was taken. Thus we concluded that under the conditions of this study the urine screening program added to hospital costs without significant benefit to the patient.", "contents": "Effectiveness of an outpatient urine screening program. We evaluated the effectiveness of a routine outpatient urinalysis screening program on a sample population of 2600 patients. The 189 abnormal urine results found in 182 patients were followed up by study of any new clinical and laboratory investigations or therapeutic modifications initiated on the basis of any abnormal test result. The urinalysis screening program appeared to have significant bearing on diagnosis or treatment in only 13 patients. Abnormalities found in 150 of the 182 patients were either not noted or no further positive action was taken. Thus we concluded that under the conditions of this study the urine screening program added to hospital costs without significant benefit to the patient."}
{"id": "PMID:21762", "title": "Criteria for establishing a standardized method for determining alkaline phosphatase activity in human serum.", "content": "We investigated factors influencing alkaline phosphatase activity in the course of developing criteria for the establishment of a standardized method for its determination in human serum at 30 degrees C. The effects of pH, phosphorylatable acceptor (2-amino-2-methyl-1-propanol and diethanolamine), 4-nitrophenyl phosphate, magnesium ion, zinc ion, temperature, volume fraction of specimen, and details of initiation of the reaction have been studied, with use of partly purified enzymes from bone, intestine, liver, and placenta, and sera from patients with a predominant characterized isoenzyme. The purity of the diethanolamine was examined and contaminant monoethanolamine was characterized as a competitive inhibitor. Two sets of recommended conditions are: 2-amino-2-methyl-1-propanol, 0.9 mol/liter; 4-nitrophenyl phosphate, 16 mmol/liter; magnesium ion, 1 mmol/liter; volume fraction of specimen 1/30, and pH30 degrees C 10.5; diethanolamine, 1.8 mol/liter; 4-nitrophenyl phosphate, 18 mmol/liter; magnesium ion, 1 mmol/liter; volume fraction of specimen 1/60, and pH30 degrees C 10.1. Serum is preincubated with all reagents but 4-nitrophenyl phosphate, which is used as the reaction-initiating substrate.", "contents": "Criteria for establishing a standardized method for determining alkaline phosphatase activity in human serum. We investigated factors influencing alkaline phosphatase activity in the course of developing criteria for the establishment of a standardized method for its determination in human serum at 30 degrees C. The effects of pH, phosphorylatable acceptor (2-amino-2-methyl-1-propanol and diethanolamine), 4-nitrophenyl phosphate, magnesium ion, zinc ion, temperature, volume fraction of specimen, and details of initiation of the reaction have been studied, with use of partly purified enzymes from bone, intestine, liver, and placenta, and sera from patients with a predominant characterized isoenzyme. The purity of the diethanolamine was examined and contaminant monoethanolamine was characterized as a competitive inhibitor. Two sets of recommended conditions are: 2-amino-2-methyl-1-propanol, 0.9 mol/liter; 4-nitrophenyl phosphate, 16 mmol/liter; magnesium ion, 1 mmol/liter; volume fraction of specimen 1/30, and pH30 degrees C 10.5; diethanolamine, 1.8 mol/liter; 4-nitrophenyl phosphate, 18 mmol/liter; magnesium ion, 1 mmol/liter; volume fraction of specimen 1/60, and pH30 degrees C 10.1. Serum is preincubated with all reagents but 4-nitrophenyl phosphate, which is used as the reaction-initiating substrate."}
{"id": "PMID:21763", "title": "Improved hydrolysis of urinary 17-hydroxycorticosteroid glucuronides with beta-glucuronidase from Helix pomatia, on adding sodium sulfate.", "content": "Sodium sulfate increases the hydrolysis of urinary 17-hydroxycorticosteroid glucuronides with beta-glucuronidase preparations derived from Helix pomatia because it removes the inhibitory activity of urinary high-molecular-weight substances. For maximum hydrolysis of urinary 17-hydroxycorticosteroid glucuronides, the hydrolysis [5 ml of urine, 0.5 ml of 2 mol/liter acetate buffer (pH 5.0)] should be conducted in the presence of sodium sulfate (final concentration: 80 g/liter) with (a) 600 Fishman units of the enzyme per milliliter of urine (18 h at 52 degrees C) or (b) with 1500 units of the enzyme per milliliter of urine (3 h at 57 degrees C). Under conditions a, analytical recovery of steroid glucuronides added to 12 urine samples was 99 +/- 2.1% (96-102%). Values obtained for 20 urine samples with this method were 99 +/- 2.7% (93-104%) as great as those yielded by a method in which 600 units of the enzyme from bovine liver are used together with sodium sulfate (18 h at 48 degrees C).", "contents": "Improved hydrolysis of urinary 17-hydroxycorticosteroid glucuronides with beta-glucuronidase from Helix pomatia, on adding sodium sulfate. Sodium sulfate increases the hydrolysis of urinary 17-hydroxycorticosteroid glucuronides with beta-glucuronidase preparations derived from Helix pomatia because it removes the inhibitory activity of urinary high-molecular-weight substances. For maximum hydrolysis of urinary 17-hydroxycorticosteroid glucuronides, the hydrolysis [5 ml of urine, 0.5 ml of 2 mol/liter acetate buffer (pH 5.0)] should be conducted in the presence of sodium sulfate (final concentration: 80 g/liter) with (a) 600 Fishman units of the enzyme per milliliter of urine (18 h at 52 degrees C) or (b) with 1500 units of the enzyme per milliliter of urine (3 h at 57 degrees C). Under conditions a, analytical recovery of steroid glucuronides added to 12 urine samples was 99 +/- 2.1% (96-102%). Values obtained for 20 urine samples with this method were 99 +/- 2.7% (93-104%) as great as those yielded by a method in which 600 units of the enzyme from bovine liver are used together with sodium sulfate (18 h at 48 degrees C)."}
{"id": "PMID:21764", "title": "Use of an enzymatic kit method for cholesterol, designed for continuous-flow instrumentation, with discrete bichromatic and centrifugal analyzers.", "content": "I examined a cholesterol-assay kit (\"Autoflo\", Biodynamics/bmc) designed for use with continuous-flow instrumentation for its use with some discrete analyzers. At pH 7.2, color develops within 3 min upon exposure to cholesterol, then begins to fade. At pH 8, the color develops more slowly but remains stable for at least 15 min after reaching a maximum. A pH 8.8, the color develops still more slowly and standards and patients' sera behave differently. Reagent at pH 7.2 is preferred because assays can be completed most rapidly, but pH 8 reagent must be used with instruments requiring longer periods of incubation. Cholesterol assays can be performed accurately, rapidly, reproducibly, and at low cost with an Abbott ABA-50 and pH 7.2 reagent or with a Gemeni Centrifugal Analyzer and the pH 8 reagent.", "contents": "Use of an enzymatic kit method for cholesterol, designed for continuous-flow instrumentation, with discrete bichromatic and centrifugal analyzers. I examined a cholesterol-assay kit (\"Autoflo\", Biodynamics/bmc) designed for use with continuous-flow instrumentation for its use with some discrete analyzers. At pH 7.2, color develops within 3 min upon exposure to cholesterol, then begins to fade. At pH 8, the color develops more slowly but remains stable for at least 15 min after reaching a maximum. A pH 8.8, the color develops still more slowly and standards and patients' sera behave differently. Reagent at pH 7.2 is preferred because assays can be completed most rapidly, but pH 8 reagent must be used with instruments requiring longer periods of incubation. Cholesterol assays can be performed accurately, rapidly, reproducibly, and at low cost with an Abbott ABA-50 and pH 7.2 reagent or with a Gemeni Centrifugal Analyzer and the pH 8 reagent."}
{"id": "PMID:21765", "title": "Oxidation of alpha-hydroxybutyrate by human serum.", "content": "2-Hydroxybutyrate is enzymically oxidized by the LDH of human serum. Optimal concentrations of hydrogen ion, substrate and coenzyme for this oxidation by sera from patients with disease of the heart or liver have been determined at 37 degrees C. The linearity of this reaction is limited to a point at which an assay procedure employing a 2-hydroxyburyrate substrate seems unsuitable.", "contents": "Oxidation of alpha-hydroxybutyrate by human serum. 2-Hydroxybutyrate is enzymically oxidized by the LDH of human serum. Optimal concentrations of hydrogen ion, substrate and coenzyme for this oxidation by sera from patients with disease of the heart or liver have been determined at 37 degrees C. The linearity of this reaction is limited to a point at which an assay procedure employing a 2-hydroxyburyrate substrate seems unsuitable."}
{"id": "PMID:21768", "title": "Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine.", "content": "The concentrations of sulfapyridine (SP) and N4-acetylsulfapyridine (AcSP) in the plasma and saliva of 5 healthy male adults (3 slow and 2 rapid acetylators) were determined as a function of time after a single 2.0-gm oral dose of sulfasalazine (salicylazosulfapyridine). SP absorption commenced 3.5 to 6 hr after sulfasalazine administration and occurred slowly (apparent absorption t1/2s ranged from 1.6 to 5 hr) irrespective of acetylator phenotype. Appreciable differences existed between slow and rapid acetylators with respect to the biologic t1/2 and total body clearance of SP. SP concentrations in the saliva correlated well with those in the plasma. The saliva:plasma concentration ratio for SP was 0.559 +/- 0.027 (mean of 5 subjects +/- SE) and was dependent of plasma concentration and saliva pH. The mean saliva:plasma concentration ratio for AcSP was lower (0.246 +/- 0.056), consistent with the pH-partition hypothesis, and showed considerably more intrasubject and intersubject variation than the ratio for SP. These findings suggest that measurement of SP concentrations in the saliva may be a convenient, noninvasive method for monitoring indirectly the steady-state plasma (serum) concentrations of SP in patients with ulcerative colitis or Crohn's disease who are receiving sulfasalazine.", "contents": "Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine. The concentrations of sulfapyridine (SP) and N4-acetylsulfapyridine (AcSP) in the plasma and saliva of 5 healthy male adults (3 slow and 2 rapid acetylators) were determined as a function of time after a single 2.0-gm oral dose of sulfasalazine (salicylazosulfapyridine). SP absorption commenced 3.5 to 6 hr after sulfasalazine administration and occurred slowly (apparent absorption t1/2s ranged from 1.6 to 5 hr) irrespective of acetylator phenotype. Appreciable differences existed between slow and rapid acetylators with respect to the biologic t1/2 and total body clearance of SP. SP concentrations in the saliva correlated well with those in the plasma. The saliva:plasma concentration ratio for SP was 0.559 +/- 0.027 (mean of 5 subjects +/- SE) and was dependent of plasma concentration and saliva pH. The mean saliva:plasma concentration ratio for AcSP was lower (0.246 +/- 0.056), consistent with the pH-partition hypothesis, and showed considerably more intrasubject and intersubject variation than the ratio for SP. These findings suggest that measurement of SP concentrations in the saliva may be a convenient, noninvasive method for monitoring indirectly the steady-state plasma (serum) concentrations of SP in patients with ulcerative colitis or Crohn's disease who are receiving sulfasalazine."}
{"id": "PMID:21770", "title": "Enzymes of Penicillium roqueforti involved in the biosynthesis of cheese flavor.", "content": "The ripening of blue and Roquefort cheeses is accomplished by the concerted and controlled actions of enzymes of the mold Penicillium roqueforti. The properties and effects of the enzymes involved in flavor development (i.e., proteases, lipase and beta-ketoacid decarboxylase) are reviewed. The metabolic activities of both spores and mycelia of P. roqueforti in relation to fatty acid metabolism and flavor generation are discussed. The chemical composition of blue cheese flavor and the simulation of this flavor by fermentation and formulation are briefly surveyed. Some nutritional aspects of blue cheese are cited.", "contents": "Enzymes of Penicillium roqueforti involved in the biosynthesis of cheese flavor. The ripening of blue and Roquefort cheeses is accomplished by the concerted and controlled actions of enzymes of the mold Penicillium roqueforti. The properties and effects of the enzymes involved in flavor development (i.e., proteases, lipase and beta-ketoacid decarboxylase) are reviewed. The metabolic activities of both spores and mycelia of P. roqueforti in relation to fatty acid metabolism and flavor generation are discussed. The chemical composition of blue cheese flavor and the simulation of this flavor by fermentation and formulation are briefly surveyed. Some nutritional aspects of blue cheese are cited."}
{"id": "PMID:21771", "title": "Carfecillin: antibacterial activity in vitro and in vivo.", "content": "Carfecillin, the alpha-phenyl ester of carbenicillin, hydrolyses rapidly in the presence of serum or body tissues to liberate carbenicillin but hydrolysis is less rapid in aqueous solution. The activity of carfecillin in antibacterial tests in vitro depends upon the extent of hydrolysis to carbenicillin, and in conventional serial dilution tests carfecillin shows an antibacterial spectrum generally similar to that of carbenicillin due to extensive hydrolysis. However, in tests in which the extent of hydrolysis is reduced, carfecillin displays lesser activity than carbenicillin against gram-negative bacilli and greater activity against gram-positive cocci. In the presence of serum carfecillin is hydrolysed rapidly to carbenicillin and the activity shown is solely that of carbenicillin. Unlike carbenicillin, carfecillin is well absorbed in mice after oral administration, producing significant carbenicillin blood concentrations and the compound is as effective by the oral route in the treatment of various experimental mouse infections as is parenteral carbenicillin.", "contents": "Carfecillin: antibacterial activity in vitro and in vivo. Carfecillin, the alpha-phenyl ester of carbenicillin, hydrolyses rapidly in the presence of serum or body tissues to liberate carbenicillin but hydrolysis is less rapid in aqueous solution. The activity of carfecillin in antibacterial tests in vitro depends upon the extent of hydrolysis to carbenicillin, and in conventional serial dilution tests carfecillin shows an antibacterial spectrum generally similar to that of carbenicillin due to extensive hydrolysis. However, in tests in which the extent of hydrolysis is reduced, carfecillin displays lesser activity than carbenicillin against gram-negative bacilli and greater activity against gram-positive cocci. In the presence of serum carfecillin is hydrolysed rapidly to carbenicillin and the activity shown is solely that of carbenicillin. Unlike carbenicillin, carfecillin is well absorbed in mice after oral administration, producing significant carbenicillin blood concentrations and the compound is as effective by the oral route in the treatment of various experimental mouse infections as is parenteral carbenicillin."}
{"id": "PMID:21773", "title": "Urinary excretion pattern of methaqualone metabolites in man.", "content": "A method based on selected ion monitoring for determination of five monohydroxy metabolites of methaqualone in urine has been worked out. By means of this method the time course of metabolite excretion was studied in three healthy volunteers receiving an oral therapeutic dose of methaqualone. In all subjects the main monohydroxy metabolite was conjugated 4'-hydroxymethaqualone, but the relative importance of the five metabolites showed intersubject variation. Metabolite excretion was still going on, when urine sampling was discontinued after 70 hr. Only small amounts (less than 1% of the dose during 70 hr) of unmetabolized methaqualone were excreted. On the other hand, it was confirmed that methaqualone-N1-oxide is an important metabolite. The presence of a hydroxy methoxy metabolite of methaqualone, very probably 4'-hydroxy-5'-methoxymethaqualone, as a minor metabolite was established by comparison with authentic, synthetic material. 8-Hydroxymethaqualone and 2-nitrobenz-o-toluidide, reported by other groups, could not be detected.", "contents": "Urinary excretion pattern of methaqualone metabolites in man. A method based on selected ion monitoring for determination of five monohydroxy metabolites of methaqualone in urine has been worked out. By means of this method the time course of metabolite excretion was studied in three healthy volunteers receiving an oral therapeutic dose of methaqualone. In all subjects the main monohydroxy metabolite was conjugated 4'-hydroxymethaqualone, but the relative importance of the five metabolites showed intersubject variation. Metabolite excretion was still going on, when urine sampling was discontinued after 70 hr. Only small amounts (less than 1% of the dose during 70 hr) of unmetabolized methaqualone were excreted. On the other hand, it was confirmed that methaqualone-N1-oxide is an important metabolite. The presence of a hydroxy methoxy metabolite of methaqualone, very probably 4'-hydroxy-5'-methoxymethaqualone, as a minor metabolite was established by comparison with authentic, synthetic material. 8-Hydroxymethaqualone and 2-nitrobenz-o-toluidide, reported by other groups, could not be detected."}
{"id": "PMID:21775", "title": "Metabolism of sulfadimidine, sulfanilamide, p-aminobenzoic acid, and isoniazid in suspensions of parenchymal and nonparenchymal rat liver cells.", "content": "Suspensions of isolated liver cells were prepared from rat livers perfused with Ca++-free buffer and 0.05% collagenase. Primary cell suspensions (containing both parenchymal and nonparenchymal liver cells) metabolized sulfadimidine, sulfanilamide, p-aminobenzoic acid, and isoniazid approximately at first order kinetics for at least 4 hr. Suspensions of parenchymal cells had the same metabolic capacity, although the metabolism of isoniazid proceeded at a somewhat reduced rate compared to the primary cell suspensions. Suspensions of nonparenchymal cells did not metabolize sulfadimidine, sulfanilamide, or p-aminobenzoic acid during 4 hr, although such suspensions acted upon isoniazid to some degree. It was concluded that parenchymal rat liver cells may metabolize (acetylate) all four drugs tested, whereas nonparenchymal cells metabolize only isoniazid to any considerable extent.", "contents": "Metabolism of sulfadimidine, sulfanilamide, p-aminobenzoic acid, and isoniazid in suspensions of parenchymal and nonparenchymal rat liver cells. Suspensions of isolated liver cells were prepared from rat livers perfused with Ca++-free buffer and 0.05% collagenase. Primary cell suspensions (containing both parenchymal and nonparenchymal liver cells) metabolized sulfadimidine, sulfanilamide, p-aminobenzoic acid, and isoniazid approximately at first order kinetics for at least 4 hr. Suspensions of parenchymal cells had the same metabolic capacity, although the metabolism of isoniazid proceeded at a somewhat reduced rate compared to the primary cell suspensions. Suspensions of nonparenchymal cells did not metabolize sulfadimidine, sulfanilamide, or p-aminobenzoic acid during 4 hr, although such suspensions acted upon isoniazid to some degree. It was concluded that parenchymal rat liver cells may metabolize (acetylate) all four drugs tested, whereas nonparenchymal cells metabolize only isoniazid to any considerable extent."}
{"id": "PMID:21776", "title": "The metabolism of drugs in isolated rat hepatocytes. A comparison with in vivo drug metabolism and drug metabolism in subcellular liver fractions.", "content": "The metabolism of drugs in isolated rat hepatocytes has been investigated. Drugs which are metabolized by aromatic hydrolation, aliphatic hydroylation, N-demethylation, or glucuronidation have been used as substrates. With some substrates the rate of metabolism in isolated hepatocytes compares with that in hepatic 900g supernatant fraction or microsomes, but other substrates are metabolized at a slower rate in isolated hepatocytes. For example, the rate of butamoxane hydroxylation in isolated hepatocytes is slower than that in microsomes. However, the rate of hydroxylation is hepatocytes is identical to that in perfused liver. The metabolism of drugs in isolated hepatocytes correlates with in vivo drug metabolism better than does metabolism in the hepatic 9000g supernatant fraction or microsomes.", "contents": "The metabolism of drugs in isolated rat hepatocytes. A comparison with in vivo drug metabolism and drug metabolism in subcellular liver fractions. The metabolism of drugs in isolated rat hepatocytes has been investigated. Drugs which are metabolized by aromatic hydrolation, aliphatic hydroylation, N-demethylation, or glucuronidation have been used as substrates. With some substrates the rate of metabolism in isolated hepatocytes compares with that in hepatic 900g supernatant fraction or microsomes, but other substrates are metabolized at a slower rate in isolated hepatocytes. For example, the rate of butamoxane hydroxylation in isolated hepatocytes is slower than that in microsomes. However, the rate of hydroxylation is hepatocytes is identical to that in perfused liver. The metabolism of drugs in isolated hepatocytes correlates with in vivo drug metabolism better than does metabolism in the hepatic 9000g supernatant fraction or microsomes."}
{"id": "PMID:21777", "title": "Comparative metabolism of four allylic barbiturates and hexobarbital by the rat and guinea pig.", "content": "A method for the extraction and identification of urinary metabolites of allylic barbiturates by gas chromatography and mass spectrometry is described. The metabolites from rat and guinea pig urine were extracted and separated into two fractions (an acidic and a nonacidic fraction) by chromatography on DEAE-Sephadex before converted into suitable derivatives for gas phase analysis. N,N'-dimethyl derivatives were used except in cases where metabolic N-demethylation was possible, in which case N-ethylation yielded more information. Hydroxyl, keto, and epoxy groups were converted into trimethylsilyl (TMS), alkyloxime, and chloro-TMS derivatives, respectively. This procedure was used to identify metabolites present in urine at concentrations as low as 0.1 microgram/ml. The allyl sidechains of secobarbital, alphenal, allobarbital, and aprobarbital were metabolized to epoxides, diols, and, in the case of secobarbital, to a ketol. Other sidechains were usually hydroxylated. Secobarbital was metabolized to compounds containing hydroxyl groups in both chains. Hexobarbital was metabolized by allylic hydroxylation, and no evidence of the epoxide-diol pathway was observed. The significance of the detection of epoxides of the four allylic barbiturates is discussed.", "contents": "Comparative metabolism of four allylic barbiturates and hexobarbital by the rat and guinea pig. A method for the extraction and identification of urinary metabolites of allylic barbiturates by gas chromatography and mass spectrometry is described. The metabolites from rat and guinea pig urine were extracted and separated into two fractions (an acidic and a nonacidic fraction) by chromatography on DEAE-Sephadex before converted into suitable derivatives for gas phase analysis. N,N'-dimethyl derivatives were used except in cases where metabolic N-demethylation was possible, in which case N-ethylation yielded more information. Hydroxyl, keto, and epoxy groups were converted into trimethylsilyl (TMS), alkyloxime, and chloro-TMS derivatives, respectively. This procedure was used to identify metabolites present in urine at concentrations as low as 0.1 microgram/ml. The allyl sidechains of secobarbital, alphenal, allobarbital, and aprobarbital were metabolized to epoxides, diols, and, in the case of secobarbital, to a ketol. Other sidechains were usually hydroxylated. Secobarbital was metabolized to compounds containing hydroxyl groups in both chains. Hexobarbital was metabolized by allylic hydroxylation, and no evidence of the epoxide-diol pathway was observed. The significance of the detection of epoxides of the four allylic barbiturates is discussed."}
{"id": "PMID:21778", "title": "Disposition of triazolam, 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a]benzodiazepine, in the dog.", "content": "Disposition of triazolam (T), a new, potent, hypnotic agent, was studied in the dog. A single 0.5-mg/kg oral or iv dose of 14C-labeled T was rapidly absorbed, and although 88% was bound to serum proteins, T levels decreased with a half-life of 0.85 hr. Metabolism of T was rapid, with a first-pass effect observed after oral administration. Excretion of drug-related materials was rapid; urinary and fecal excretion of 14C were equal. Urine contained no measurable T, and metabolites were mostly conjugated. The major urinary metabolite was the alpha-HT analog of T, resulting from oxidation of the 1-methyl group of the triazole moiety. Other metabolites identified were the 4-hydroxy and alpha,4-hHT analogs of T, as well as the 1-demethyl analog, which probably results from further oxidation of alpha-hydroxy-T. Evidence also was obtained for two other monohydroxy analogs plus a dihydroxy, monohydroxymonomethoxy, and a dihydroxymonomethoxy analog of triazolam.", "contents": "Disposition of triazolam, 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a]benzodiazepine, in the dog. Disposition of triazolam (T), a new, potent, hypnotic agent, was studied in the dog. A single 0.5-mg/kg oral or iv dose of 14C-labeled T was rapidly absorbed, and although 88% was bound to serum proteins, T levels decreased with a half-life of 0.85 hr. Metabolism of T was rapid, with a first-pass effect observed after oral administration. Excretion of drug-related materials was rapid; urinary and fecal excretion of 14C were equal. Urine contained no measurable T, and metabolites were mostly conjugated. The major urinary metabolite was the alpha-HT analog of T, resulting from oxidation of the 1-methyl group of the triazole moiety. Other metabolites identified were the 4-hydroxy and alpha,4-hHT analogs of T, as well as the 1-demethyl analog, which probably results from further oxidation of alpha-hydroxy-T. Evidence also was obtained for two other monohydroxy analogs plus a dihydroxy, monohydroxymonomethoxy, and a dihydroxymonomethoxy analog of triazolam."}
{"id": "PMID:21783", "title": "[Maridi haemorrhgic fever: a new viral disease (author's transl)].", "content": "A new viral disease (Maridi haemorrhagic fever) occurred in the South Sudan in 1976. It was obviously identical with an epidemic which occurred at the same time in Zaire. The virus is morpologically closely similar to the Marburg virus. During the Maridi epemic 124 of 238 patients died (52%). Characteristic symptoms were fever and headache (100%), diarrhoea (83%), retrosternal pain (82%), vomiting (68%), haemorrhages (62%), morbilliform or vesicular rash (52%). At post-mortem there were changes in liver, kidney, myocardium and lungs, similar to those in the Marburg virus disease, as were those observed in bone marrow and peripheral blood. Despite these analagous findings, the clinical course and results of immunofluorescence indicate that it is a new disease. The epidemic ended after suitable isolation measures had been taken. There was no specific treatment but in some cases convalescent plasma and interferon were tried. The disease is transmitted among humans by direct contact or by contact with blood or excreta of patients. No animal reservoir has been found. It is possible for this disease to be imported also into countries with a modorate climate.", "contents": "[Maridi haemorrhgic fever: a new viral disease (author's transl)]. A new viral disease (Maridi haemorrhagic fever) occurred in the South Sudan in 1976. It was obviously identical with an epidemic which occurred at the same time in Zaire. The virus is morpologically closely similar to the Marburg virus. During the Maridi epemic 124 of 238 patients died (52%). Characteristic symptoms were fever and headache (100%), diarrhoea (83%), retrosternal pain (82%), vomiting (68%), haemorrhages (62%), morbilliform or vesicular rash (52%). At post-mortem there were changes in liver, kidney, myocardium and lungs, similar to those in the Marburg virus disease, as were those observed in bone marrow and peripheral blood. Despite these analagous findings, the clinical course and results of immunofluorescence indicate that it is a new disease. The epidemic ended after suitable isolation measures had been taken. There was no specific treatment but in some cases convalescent plasma and interferon were tried. The disease is transmitted among humans by direct contact or by contact with blood or excreta of patients. No animal reservoir has been found. It is possible for this disease to be imported also into countries with a modorate climate."}
{"id": "PMID:21780", "title": "Studies on isometheptene metabolism. Identification and stereochemistry of a major metabolite isolated from rat urine.", "content": "By gas chromatography-mass spectrometry of both underivatized samples and N-acetates, the major urinary metabolite of the antispasmodic drug (+/-)-isometheptene in the rat was identified as trans-2-methyl-6-methylamino-2-hepten-1-ol. The structure and stereochemistry of the metabolites was confirmed by comparing the properties of its N-acetate with those of an authentic sample of the N-acetate of trans-2-methyl-6-methylamino-2-hepten-1-ol which was obtained by a stereospecific trans-allylic hydroxylation of isometheptene acetate with selenium dioxide in ethanol. cis-2-Methyl-6-methylamino-2-hepten-1-ol was identified as a minor urinary metabolite of isometheptene in the rat.", "contents": "Studies on isometheptene metabolism. Identification and stereochemistry of a major metabolite isolated from rat urine. By gas chromatography-mass spectrometry of both underivatized samples and N-acetates, the major urinary metabolite of the antispasmodic drug (+/-)-isometheptene in the rat was identified as trans-2-methyl-6-methylamino-2-hepten-1-ol. The structure and stereochemistry of the metabolites was confirmed by comparing the properties of its N-acetate with those of an authentic sample of the N-acetate of trans-2-methyl-6-methylamino-2-hepten-1-ol which was obtained by a stereospecific trans-allylic hydroxylation of isometheptene acetate with selenium dioxide in ethanol. cis-2-Methyl-6-methylamino-2-hepten-1-ol was identified as a minor urinary metabolite of isometheptene in the rat."}
{"id": "PMID:21785", "title": "[Treatment of peptic ulcer in the Zollinger-Ellison syndrome with histamine H2-receptor antagonists (author's transl)].", "content": "Histamine H2-receptor antagonists metiamide and cimetidine were used in the treatment of severe peptic ulceration in Zollinger-Ellison syndrome. The ulcerations were completely healed in all four patients after treatment lasting from six weeks to four-and-a-half-months. Two patients developed recurrent ulcer after the treatment had stopped, but responded to a second course. One patient developed hepatitis B during cimetidine treatment and it is possible that the course of the hepatitis was unfavourable affected by cimetidine. But no other side effects were noted nor was there a significant change in basal serum-gastrin concentration or an increase in H+ secretion. Total gastrectomy remains the treatment of choice in Zollinger-Ellison syndrome, but cimetidine should be considered if the patient refuses operation or operation is not feasible because of a poor general state.", "contents": "[Treatment of peptic ulcer in the Zollinger-Ellison syndrome with histamine H2-receptor antagonists (author's transl)]. Histamine H2-receptor antagonists metiamide and cimetidine were used in the treatment of severe peptic ulceration in Zollinger-Ellison syndrome. The ulcerations were completely healed in all four patients after treatment lasting from six weeks to four-and-a-half-months. Two patients developed recurrent ulcer after the treatment had stopped, but responded to a second course. One patient developed hepatitis B during cimetidine treatment and it is possible that the course of the hepatitis was unfavourable affected by cimetidine. But no other side effects were noted nor was there a significant change in basal serum-gastrin concentration or an increase in H+ secretion. Total gastrectomy remains the treatment of choice in Zollinger-Ellison syndrome, but cimetidine should be considered if the patient refuses operation or operation is not feasible because of a poor general state."}
{"id": "PMID:21786", "title": "[Minoxidil in the treatment of malignant hypertension (author's transl)].", "content": "In 21 of 23 patients with hypertension unresponsive to other treatment minoxidil, a new antihypertensive drug acting via peripheral vasodilatation, lowered their blood pressure from 191 +/- 19/117 +/- 12 MM Hg to 147 +/- 13/117 +/- 12 mm Hg. The drug causes a reflex tachycardia and must therefore be combined with beta-blockers. Furthermore, an effective diuretic must also be used because minoxidil causes sodium retention. Hypertrichosis is an important side-effect for which the drug may have to be discontinued, especially in young women. Orthostasis did not occur in the reported series. The authors recommend that the drug be made available for the treatment of malignant hypertension.", "contents": "[Minoxidil in the treatment of malignant hypertension (author's transl)]. In 21 of 23 patients with hypertension unresponsive to other treatment minoxidil, a new antihypertensive drug acting via peripheral vasodilatation, lowered their blood pressure from 191 +/- 19/117 +/- 12 MM Hg to 147 +/- 13/117 +/- 12 mm Hg. The drug causes a reflex tachycardia and must therefore be combined with beta-blockers. Furthermore, an effective diuretic must also be used because minoxidil causes sodium retention. Hypertrichosis is an important side-effect for which the drug may have to be discontinued, especially in young women. Orthostasis did not occur in the reported series. The authors recommend that the drug be made available for the treatment of malignant hypertension."}
{"id": "PMID:21782", "title": "The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide in mice and rats.", "content": "The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA; NSC-141549), a new antitumor agent presently under consideration for phase I evaluation in man, was studied in mice and rats with 14C-AMSA labeled in the 9-carbon of the acridine ring. Radioactivity was selectively localized in the liver where it was present mainly as metabolites of AMSA. After 2 hr, nearly 50% of the plasma radioactivity was bound to protein and did not dissociate upon Sephadex G-200 chromatography. Radioactivity was rapidly eliminated in the bile; greater than 50% of the administered dose was excreted by this route in 2 hr. Bile/plasma ratios of greater than 400:1 indicated an active transport mechanism. The biliary transport mechanism was saturable with therapeutic doses. AMSA was found to be especially vulnerable to nucleophilic attack by alkylthiols resulting in displacement of 4-amino-3-methoxymethanesulfonanilide and the formation of the corresponding 9-alkylthioether of acridine. The major radioactive biliary metabolite (accounting for 90-95% of the biliary radioactivity) possessed the same chromatographic properties as the thiolysis product of AMSA and glutathione (GSH). A 40% reduction in liver GSH and a 20% reduction of liver GSH-transferase activity occurred after AMSA administration to mice. The pharmacologic disposition of AMSA can best be explained by a nonenzymatic nucleophilic attack on the 9-carbon atom of AMSA by endogenous thiols, resulting in the formation of 9-thioethers of acridine. Such an attack by low molecular weight thiols results in a product that is eliminated in urine and bile, whereas interaction with protein-thiol groups results in prolonged retention of the acridine moiety.", "contents": "The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide in mice and rats. The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA; NSC-141549), a new antitumor agent presently under consideration for phase I evaluation in man, was studied in mice and rats with 14C-AMSA labeled in the 9-carbon of the acridine ring. Radioactivity was selectively localized in the liver where it was present mainly as metabolites of AMSA. After 2 hr, nearly 50% of the plasma radioactivity was bound to protein and did not dissociate upon Sephadex G-200 chromatography. Radioactivity was rapidly eliminated in the bile; greater than 50% of the administered dose was excreted by this route in 2 hr. Bile/plasma ratios of greater than 400:1 indicated an active transport mechanism. The biliary transport mechanism was saturable with therapeutic doses. AMSA was found to be especially vulnerable to nucleophilic attack by alkylthiols resulting in displacement of 4-amino-3-methoxymethanesulfonanilide and the formation of the corresponding 9-alkylthioether of acridine. The major radioactive biliary metabolite (accounting for 90-95% of the biliary radioactivity) possessed the same chromatographic properties as the thiolysis product of AMSA and glutathione (GSH). A 40% reduction in liver GSH and a 20% reduction of liver GSH-transferase activity occurred after AMSA administration to mice. The pharmacologic disposition of AMSA can best be explained by a nonenzymatic nucleophilic attack on the 9-carbon atom of AMSA by endogenous thiols, resulting in the formation of 9-thioethers of acridine. Such an attack by low molecular weight thiols results in a product that is eliminated in urine and bile, whereas interaction with protein-thiol groups results in prolonged retention of the acridine moiety."}
{"id": "PMID:21787", "title": "[Defluoridation of household water].", "content": "Fluorine enriched drinking water (1 ppm F-) is partially defluoridated with the aid of a simple (laboratory) apparatus. The material employed is tricalcium phosphate. The pH-values and electrical conductivity due to fluoridation are significantly changed by defluoridation. The duration of the defluoridation process appears acceptable and the efficiency of the system is adequate. The experimental conditions as well as the results show that an acceptable alternative exists to fluoridated drinking water in the household.", "contents": "[Defluoridation of household water]. Fluorine enriched drinking water (1 ppm F-) is partially defluoridated with the aid of a simple (laboratory) apparatus. The material employed is tricalcium phosphate. The pH-values and electrical conductivity due to fluoridation are significantly changed by defluoridation. The duration of the defluoridation process appears acceptable and the efficiency of the system is adequate. The experimental conditions as well as the results show that an acceptable alternative exists to fluoridated drinking water in the household."}
{"id": "PMID:21788", "title": "[Local anesthesia and beta receptor blockers in dentistry. (Study on an injectable combination of lidocaine and betadrenol)].", "content": "A double blind trial was undertaken to determine whether the addition of the beta-receptor blocker Betadrenol in two different doses to a lidocaine solution containing adrenaline could influence the exogenous and endogenous beta-adrenergic effects in the field of dental interventions under local anesthesia. It could be shown that already very small amounts of the beta-receptor blocker Betadrenol could suspend beta-adrenergic stimulation of the heart and so prevent unwanted circulatory reactions without side effects on the central nervous system.", "contents": "[Local anesthesia and beta receptor blockers in dentistry. (Study on an injectable combination of lidocaine and betadrenol)]. A double blind trial was undertaken to determine whether the addition of the beta-receptor blocker Betadrenol in two different doses to a lidocaine solution containing adrenaline could influence the exogenous and endogenous beta-adrenergic effects in the field of dental interventions under local anesthesia. It could be shown that already very small amounts of the beta-receptor blocker Betadrenol could suspend beta-adrenergic stimulation of the heart and so prevent unwanted circulatory reactions without side effects on the central nervous system."}
{"id": "PMID:21789", "title": "[Effects of clonazepam taken per os by children with rebellious epileptic encephalopathies].", "content": "The effect of clonazepam, taken per-os and in very progressive doses, has been studied by the authors on fourteen children afflicted with evolutive epileptic encephalopathies and still presenting, in spite of heavy anti-epileptic polychemio-therapies, alarming clinical and electrical manifestations. Clonazepam proved to be an efficient contributive factor in the course of a curing process since, in 70% of the cases, it produced quite a visible amelioration. Its efficient action seems to last longer than that of other diazepines since half of their patients have now been treated with it for more than a year with, as a result, a constant clinical and electrical amelioration. As a last point, it appears to be a very useful drug when dealing with type of rebellious epilepsies since, when combined with other benzodiazepines, seldom side-effects and no \"crossed resistances\" can be observed.", "contents": "[Effects of clonazepam taken per os by children with rebellious epileptic encephalopathies]. The effect of clonazepam, taken per-os and in very progressive doses, has been studied by the authors on fourteen children afflicted with evolutive epileptic encephalopathies and still presenting, in spite of heavy anti-epileptic polychemio-therapies, alarming clinical and electrical manifestations. Clonazepam proved to be an efficient contributive factor in the course of a curing process since, in 70% of the cases, it produced quite a visible amelioration. Its efficient action seems to last longer than that of other diazepines since half of their patients have now been treated with it for more than a year with, as a result, a constant clinical and electrical amelioration. As a last point, it appears to be a very useful drug when dealing with type of rebellious epilepsies since, when combined with other benzodiazepines, seldom side-effects and no \"crossed resistances\" can be observed."}
{"id": "PMID:21790", "title": "Enzymes of nitrogen metabolism in legume nodules. Purification and properties of NADH-dependent glutamate synthase from lupin nodules.", "content": "An NADH-dependent glutamate synthase has been purified 500-fold from the plant cytoplasm fraction of Lupinus angustifolius nodules. It consists of a single polypeptide chain, Mr 235000. The optimum  pH is 8.5, at which Km values for 2-oxoglutarate, glutamine and NADH are 39 micrometer, 400 micrometer and 1.3 micrometer respectively. The catalytic centre activity is of the order of 70 s-1 and is independent of pH between 6.5 and 9.5. Glutamate synthase is inhibited by glutamic acid, oxaloacetic acid, aspartic acid and asparagine, all competitive with 2-oxoglutarate; and by NAD+, which is competitive with NADH. There is evidence of two flavine prosthetic groups per enzyme molecule.", "contents": "Enzymes of nitrogen metabolism in legume nodules. Purification and properties of NADH-dependent glutamate synthase from lupin nodules. An NADH-dependent glutamate synthase has been purified 500-fold from the plant cytoplasm fraction of Lupinus angustifolius nodules. It consists of a single polypeptide chain, Mr 235000. The optimum  pH is 8.5, at which Km values for 2-oxoglutarate, glutamine and NADH are 39 micrometer, 400 micrometer and 1.3 micrometer respectively. The catalytic centre activity is of the order of 70 s-1 and is independent of pH between 6.5 and 9.5. Glutamate synthase is inhibited by glutamic acid, oxaloacetic acid, aspartic acid and asparagine, all competitive with 2-oxoglutarate; and by NAD+, which is competitive with NADH. There is evidence of two flavine prosthetic groups per enzyme molecule."}
{"id": "PMID:21791", "title": "Immobilization of yeast microbodies by inclusion with photo-crosslinkable resins.", "content": "Yeast microbodies containing FAD-dependent alcohol oxidase, catalase and D-amino acid oxidase were isolated from methanol-grown cells of Kloeckera sp. 2201 and immobilized intact in matrices formed by a short-time illumination of photo-crosslinkable resin oligomers. The relative activities of catalase, alcohol oxidase and D-amino acid oxidase of the gel-entrapped microbodies were 36, 76 and 31% respectively as compared with those of free microbodies. Immobilization enhance d the stability of catalase to a certain degree, but not that of alcohol oxidase. The pH/activity profiles of catalase and alcohol oxidase of the entrapped organelles showed more narrow pH optima than those of the free counterparts. D-Amino acid oxidase in immobilized microbodies showed a somewhat higher Km value for D-alanine than that in free ones. Immobilized microbodies oxidized two moles of methanol to form two moles of formaldehyde with consumption of one mole of molecular oxygen. Addition of 3-amino-1,2,4-triazole, an inhibitor of catalase, reduced the formation of formaldehyde to half the amount without change in the amount of oxygen consumed, indicating the synergic action of alcohol oxidase and catalase in methanol oxidation in the microbodies of living yeast cells.", "contents": "Immobilization of yeast microbodies by inclusion with photo-crosslinkable resins. Yeast microbodies containing FAD-dependent alcohol oxidase, catalase and D-amino acid oxidase were isolated from methanol-grown cells of Kloeckera sp. 2201 and immobilized intact in matrices formed by a short-time illumination of photo-crosslinkable resin oligomers. The relative activities of catalase, alcohol oxidase and D-amino acid oxidase of the gel-entrapped microbodies were 36, 76 and 31% respectively as compared with those of free microbodies. Immobilization enhance d the stability of catalase to a certain degree, but not that of alcohol oxidase. The pH/activity profiles of catalase and alcohol oxidase of the entrapped organelles showed more narrow pH optima than those of the free counterparts. D-Amino acid oxidase in immobilized microbodies showed a somewhat higher Km value for D-alanine than that in free ones. Immobilized microbodies oxidized two moles of methanol to form two moles of formaldehyde with consumption of one mole of molecular oxygen. Addition of 3-amino-1,2,4-triazole, an inhibitor of catalase, reduced the formation of formaldehyde to half the amount without change in the amount of oxygen consumed, indicating the synergic action of alcohol oxidase and catalase in methanol oxidation in the microbodies of living yeast cells."}
{"id": "PMID:21792", "title": "Energy requirements for maltose transport in yeast.", "content": "Maltose transport in yeast (Saccharomyces cerevisiae) is inhibited by uncouplers under conditions where the intracellular concentration of the sugar is lower than in the medium. The uncouplers did not deplete the ATP content of the yeast cells and a 50--100-fold reduction in ATP caused by antimycin and 2-deoxyglucose had no effect on maltose transport. In ATP-depleted cells, the maltose transported is partially hydrolyzed to glucose but not further metabolized and therefore a mechanism of transport involving phosphorylation can be discarded. One proton is cotransported with every maltose molecule. The fact that maltose transport is inhibited by KCl but not by NaCl, Tris-Cl or KSCN suggest that the electroneutrality during maltose and proton uptake can be maintained by the exit of K+ from the cells or by the entry of a permeable anion as SCN-. These results indicate that the translocation of maltose across the yeast plasma membrane is not dependent on ATP and is coupled to the electrochemical gradient of protons in this membrane. When this gradient is abolished by uncouplers, the transport system is not able to function even in favour of a concentration gradient of the sugar.", "contents": "Energy requirements for maltose transport in yeast. Maltose transport in yeast (Saccharomyces cerevisiae) is inhibited by uncouplers under conditions where the intracellular concentration of the sugar is lower than in the medium. The uncouplers did not deplete the ATP content of the yeast cells and a 50--100-fold reduction in ATP caused by antimycin and 2-deoxyglucose had no effect on maltose transport. In ATP-depleted cells, the maltose transported is partially hydrolyzed to glucose but not further metabolized and therefore a mechanism of transport involving phosphorylation can be discarded. One proton is cotransported with every maltose molecule. The fact that maltose transport is inhibited by KCl but not by NaCl, Tris-Cl or KSCN suggest that the electroneutrality during maltose and proton uptake can be maintained by the exit of K+ from the cells or by the entry of a permeable anion as SCN-. These results indicate that the translocation of maltose across the yeast plasma membrane is not dependent on ATP and is coupled to the electrochemical gradient of protons in this membrane. When this gradient is abolished by uncouplers, the transport system is not able to function even in favour of a concentration gradient of the sugar."}
{"id": "PMID:21794", "title": "Early biochemical and hemodynamic changes after operation in a bloodless field.", "content": "Biochemical and hemodynamic changes during and after operation in a bloodless field have been investigated in 13 patients. The patients were athletes between the age of 21 and 38 years who were healthy except for an inveterate ligament injury of the knee joint. Capillary blood flow in the tibialis anterior muscle was measured by the radioactive-Xenon-clearance technique. Fine plastic catheters for blood sampling were inserted into both femoral veins and into one radial artery. A significant increase in blood flow occurred immediately after release of the occlusion. After release of the tourniquet, there was a marked decrease in pH both in the venous blood draining the operated leg and in the arterial blood. 40 min after release of the tourniquet, there was still a significant decrease in base excess. An increase of venous pO2 in the blood draining the operated leg was observed after re-establishment of blood flow. The estimated oxygen consumption was increased in the operated leg the first 10 min after tourniquet release.", "contents": "Early biochemical and hemodynamic changes after operation in a bloodless field. Biochemical and hemodynamic changes during and after operation in a bloodless field have been investigated in 13 patients. The patients were athletes between the age of 21 and 38 years who were healthy except for an inveterate ligament injury of the knee joint. Capillary blood flow in the tibialis anterior muscle was measured by the radioactive-Xenon-clearance technique. Fine plastic catheters for blood sampling were inserted into both femoral veins and into one radial artery. A significant increase in blood flow occurred immediately after release of the occlusion. After release of the tourniquet, there was a marked decrease in pH both in the venous blood draining the operated leg and in the arterial blood. 40 min after release of the tourniquet, there was still a significant decrease in base excess. An increase of venous pO2 in the blood draining the operated leg was observed after re-establishment of blood flow. The estimated oxygen consumption was increased in the operated leg the first 10 min after tourniquet release."}
{"id": "PMID:21797", "title": "Acute acetylsalicylic acid poisoning: treatment with forced alkaline diuresis and diuretics.", "content": "101 patients were treated for acute acetylsalicylic acid (ASA) poisoning in the Nephrological Unit Trondheim between 1971-1975. On admission 33 of them had a serum salicylic acid (SA) concentration greater than 400 microgram/ml (mean 588 +/- 40 microgram/ml). This group was compared with a group of 11 children less than 5 years old with ASA poisoning and a mean serum SA on admission of 550 +/- 34 microgram/ml. Blood pH on admission was normal or elevated in all patients more than 12 years old (mean 7.43 +/- 0.01), whereas 7 of the 11 children suffered from metabolic acidosis. The results of forced alkaline diuresis produced by loop diuretics (bumetanide, furosemide) in ASA poisoned patients older than 12 years are reported. The mean T 1/2 of SA was 9.6 h in the treated group as compared to 18-22 h in untreated patients. There was no apparent difference between the diuretic effect of bumetanide and furosemide.", "contents": "Acute acetylsalicylic acid poisoning: treatment with forced alkaline diuresis and diuretics. 101 patients were treated for acute acetylsalicylic acid (ASA) poisoning in the Nephrological Unit Trondheim between 1971-1975. On admission 33 of them had a serum salicylic acid (SA) concentration greater than 400 microgram/ml (mean 588 +/- 40 microgram/ml). This group was compared with a group of 11 children less than 5 years old with ASA poisoning and a mean serum SA on admission of 550 +/- 34 microgram/ml. Blood pH on admission was normal or elevated in all patients more than 12 years old (mean 7.43 +/- 0.01), whereas 7 of the 11 children suffered from metabolic acidosis. The results of forced alkaline diuresis produced by loop diuretics (bumetanide, furosemide) in ASA poisoned patients older than 12 years are reported. The mean T 1/2 of SA was 9.6 h in the treated group as compared to 18-22 h in untreated patients. There was no apparent difference between the diuretic effect of bumetanide and furosemide."}
{"id": "PMID:21798", "title": "Autacoid and anaphylactic reactivity of pulmonary and hepatic smooth musculature of the cat.", "content": "Histamine, 2-methylhistamine (2-MeH: a relatively specific H1 receptor agonist), 5-HT, carbachol, bradykinin (BK) and PGF2alpha contract isolated cat pulmonary vein, artery and hepatic vein. PGE1, PGF2alpha and 4-methylhistamine (4-MeH: a relatively specific H2-receptor agonist) contract pulmonary arterial strips but further increase in the dose of PGE1 produces relaxation. Isoproterenol relaxes partially contracted blood vessels at low doses, but contracts at high doses. Cat trachea contracts to 5-HT, acetylcholine and carbachol but is insensitive to histamine, its analogues, BK and PGF2alpha. However, partially contracted trachea relaxes to histamine, 4-MeH, 2-MeH, isoprenaline, BK, PGE1, E2 and F2alpha. PGF2alpha and SRS-A contract cat bronchus. Isoprenaline, PGE1 and E2 relax cat bronchus contracted to carbachol, 5-HT, PGF2alpha, SRS-A and antigen. The in vitro anaphylactic contraction (Schultz-Dale reaction) of isolated pulmonary and hepatic veins, bronchus and trachea from horse plasma sensitized cat suggested the involvement of lung and liver in anaphylaxis of the cat.", "contents": "Autacoid and anaphylactic reactivity of pulmonary and hepatic smooth musculature of the cat. Histamine, 2-methylhistamine (2-MeH: a relatively specific H1 receptor agonist), 5-HT, carbachol, bradykinin (BK) and PGF2alpha contract isolated cat pulmonary vein, artery and hepatic vein. PGE1, PGF2alpha and 4-methylhistamine (4-MeH: a relatively specific H2-receptor agonist) contract pulmonary arterial strips but further increase in the dose of PGE1 produces relaxation. Isoproterenol relaxes partially contracted blood vessels at low doses, but contracts at high doses. Cat trachea contracts to 5-HT, acetylcholine and carbachol but is insensitive to histamine, its analogues, BK and PGF2alpha. However, partially contracted trachea relaxes to histamine, 4-MeH, 2-MeH, isoprenaline, BK, PGE1, E2 and F2alpha. PGF2alpha and SRS-A contract cat bronchus. Isoprenaline, PGE1 and E2 relax cat bronchus contracted to carbachol, 5-HT, PGF2alpha, SRS-A and antigen. The in vitro anaphylactic contraction (Schultz-Dale reaction) of isolated pulmonary and hepatic veins, bronchus and trachea from horse plasma sensitized cat suggested the involvement of lung and liver in anaphylaxis of the cat."}
{"id": "PMID:21799", "title": "Effects of histamine on the human penis muscle in vitro.", "content": "Histamine produced three types of effects on corpus cavernosa muscle of the human penis: contraction, relaxation or a contraction followed by a relaxation. 2-Methylhistamine, which acts mainly on histamine H1-receptors, stimulated all the penile strips tested. 4-Methylhistamine, which acts predominantly on H2-receptors produced relaxation in two-thirds of the strips and contraction in the rest. Contractions produced by histamine, 2-methyl histamine and 4-methylhistamine were selectively abolished by mepyramine. Burimamide antagonised the relaxant effect of histamine and of 4-methylhistamine. Corpus cavernosa muscle of the human penis has both histamine H1- and H2-receptors.", "contents": "Effects of histamine on the human penis muscle in vitro. Histamine produced three types of effects on corpus cavernosa muscle of the human penis: contraction, relaxation or a contraction followed by a relaxation. 2-Methylhistamine, which acts mainly on histamine H1-receptors, stimulated all the penile strips tested. 4-Methylhistamine, which acts predominantly on H2-receptors produced relaxation in two-thirds of the strips and contraction in the rest. Contractions produced by histamine, 2-methyl histamine and 4-methylhistamine were selectively abolished by mepyramine. Burimamide antagonised the relaxant effect of histamine and of 4-methylhistamine. Corpus cavernosa muscle of the human penis has both histamine H1- and H2-receptors."}
{"id": "PMID:21800", "title": "Effect of diazoxide, verapamil and compound D600 on isoproterenol and calcium-mediated dose-response relationships in isolated rabbit atrium.", "content": "The effect of diazoxide, verapamil and compound D600 on calcium and isoproterenol dose-response relationships was investigated in isolated rabbit atrial preparations. All three agents shifted calcium dose-force relationships parallel and to the right. D600 acted as a competitive antagonist of calcium, as a plot of log (x - 1) vs. -log B resulted in a straight line with a slope of approximately -1.0. Diazoxide, verapamil and D600 also antagonized isoproterenol but in a non-competitive manner. A reduction of calcium in the bathing fluid produced a qualitatively similar non-competitive antagonism of isoproterenol and markedly potentiated diazoxide antagonism of isoproterenol. We conclude that: (1) diazoxide has calcium antagonistic properties similar to the \"calcium antagonists\" verapamil and D600; (2) these agents act as competitive antagonists of calcium through a specific site that is beyond the beta-adrenergic receptor and in the series of events between the beta-adrenergic receptors and inotropic response in myocardial tissue.", "contents": "Effect of diazoxide, verapamil and compound D600 on isoproterenol and calcium-mediated dose-response relationships in isolated rabbit atrium. The effect of diazoxide, verapamil and compound D600 on calcium and isoproterenol dose-response relationships was investigated in isolated rabbit atrial preparations. All three agents shifted calcium dose-force relationships parallel and to the right. D600 acted as a competitive antagonist of calcium, as a plot of log (x - 1) vs. -log B resulted in a straight line with a slope of approximately -1.0. Diazoxide, verapamil and D600 also antagonized isoproterenol but in a non-competitive manner. A reduction of calcium in the bathing fluid produced a qualitatively similar non-competitive antagonism of isoproterenol and markedly potentiated diazoxide antagonism of isoproterenol. We conclude that: (1) diazoxide has calcium antagonistic properties similar to the \"calcium antagonists\" verapamil and D600; (2) these agents act as competitive antagonists of calcium through a specific site that is beyond the beta-adrenergic receptor and in the series of events between the beta-adrenergic receptors and inotropic response in myocardial tissue."}
{"id": "PMID:21801", "title": "Haemodynamic and baroreceptor responses to beta-adrenoceptor blocking agents in rabbits with cardiopulmonary bypass.", "content": "Blood pressure and peripheral resistance were reduced, baroreceptor activity was enhanced after i.v. infusion of beta-adrenoceptor blocking agents in rabbits with intact circulation or with total cardiopulmonary bypass. The latter preparation allowed cardiac effects of the drugs to be excluded. In rabbits with an intact circulation, post-ganglionic sympathetic activity was reduced. These results suggest a direct vascular action of the drugs. The increased baroreceptor firing is not a cardiac-mediated effect and may partly induce the observed reduction in sympathetic activity.", "contents": "Haemodynamic and baroreceptor responses to beta-adrenoceptor blocking agents in rabbits with cardiopulmonary bypass. Blood pressure and peripheral resistance were reduced, baroreceptor activity was enhanced after i.v. infusion of beta-adrenoceptor blocking agents in rabbits with intact circulation or with total cardiopulmonary bypass. The latter preparation allowed cardiac effects of the drugs to be excluded. In rabbits with an intact circulation, post-ganglionic sympathetic activity was reduced. These results suggest a direct vascular action of the drugs. The increased baroreceptor firing is not a cardiac-mediated effect and may partly induce the observed reduction in sympathetic activity."}
{"id": "PMID:21802", "title": "Release of spasmogens from rat isolated lungs by tryptamines.", "content": "Tryptamine and 5-hydroxytryptamine (5-HT) infused through the pulmonary circulation of rat isolated lungs released a spasmogen resembling slow reacting substance of anaphylaxis which we have denoted SRS-T and a PGE-like activity. SRS-T was not extractable from Krebs solution by several organic solvents at neutral or acid pH. It is therefore unlike other types of SRS activity. The PGE-like release had a threshold at about 2 microgram/ml of tryptamine or 5-HT and did not increase with increasing doses (up to 10 microgram/ml); this release was abolished by methysergide, BC 105 and BW 501c67 but not by morphine. Comparison of agonist potencies of 5-HT and tryptamine on rat stomach strip and rat pulmonary artery and of antagonist potencies of methysergide, BC 105 and morphine on these tryptamine receptors lead to the conclusion that the release receptors are unlike either of the myotropic receptors. In terms of antagonist specificity the release receptors are closest to those in rat stomach strip.", "contents": "Release of spasmogens from rat isolated lungs by tryptamines. Tryptamine and 5-hydroxytryptamine (5-HT) infused through the pulmonary circulation of rat isolated lungs released a spasmogen resembling slow reacting substance of anaphylaxis which we have denoted SRS-T and a PGE-like activity. SRS-T was not extractable from Krebs solution by several organic solvents at neutral or acid pH. It is therefore unlike other types of SRS activity. The PGE-like release had a threshold at about 2 microgram/ml of tryptamine or 5-HT and did not increase with increasing doses (up to 10 microgram/ml); this release was abolished by methysergide, BC 105 and BW 501c67 but not by morphine. Comparison of agonist potencies of 5-HT and tryptamine on rat stomach strip and rat pulmonary artery and of antagonist potencies of methysergide, BC 105 and morphine on these tryptamine receptors lead to the conclusion that the release receptors are unlike either of the myotropic receptors. In terms of antagonist specificity the release receptors are closest to those in rat stomach strip."}
{"id": "PMID:21803", "title": "The mode of contractile action of palytoxin on vascular smooth muscle.", "content": "Experiments were designed to assess the mode of action of palytoxin (PTX), isolated from Palythoa tuberculosa, on mechanically denervated rabbit aortic strips. PTX induced a sustained contraction in the muscle dose dependently. The contraction was irreversible. In the depolarized aorta, PTX did not induce a contraction whereas norepinephrine (NE) did. Removal of calcium from the bathing medium prevented PTX and high K+ contractions, whereas phasic responses were elicited by NE. D600 also inhibited the contraction induced by PTX or high K+ but had a lesser effect on that induced by NE. Sodium nitroprusside inhibited only the effect of NE. PTX increased dose dependently the 45Ca uptake of a fraction not removable by La3+ treatment and the increase was inhibited by D600. High K+ also increased the 45Ca uptake although NE did not. It is suggested that PTX increased Ca2+ influx into the smooth muscle cell to cause a contraction, which may be analogous to the action of high K+.", "contents": "The mode of contractile action of palytoxin on vascular smooth muscle. Experiments were designed to assess the mode of action of palytoxin (PTX), isolated from Palythoa tuberculosa, on mechanically denervated rabbit aortic strips. PTX induced a sustained contraction in the muscle dose dependently. The contraction was irreversible. In the depolarized aorta, PTX did not induce a contraction whereas norepinephrine (NE) did. Removal of calcium from the bathing medium prevented PTX and high K+ contractions, whereas phasic responses were elicited by NE. D600 also inhibited the contraction induced by PTX or high K+ but had a lesser effect on that induced by NE. Sodium nitroprusside inhibited only the effect of NE. PTX increased dose dependently the 45Ca uptake of a fraction not removable by La3+ treatment and the increase was inhibited by D600. High K+ also increased the 45Ca uptake although NE did not. It is suggested that PTX increased Ca2+ influx into the smooth muscle cell to cause a contraction, which may be analogous to the action of high K+."}
{"id": "PMID:21804", "title": "Effects of palytoxin on the electrical activity of dog and rabbit heart.", "content": "Reversible effects of palytoxin, extracted from colonies of the soft coral Palythoa caribaeorum, are described. There is a decrease of both membrane resting potential and overshoot during activity. Rise time of the action potential is prolonged, while repolarization is shortened. The electrical events resemble those seen with metabolic poisons.", "contents": "Effects of palytoxin on the electrical activity of dog and rabbit heart. Reversible effects of palytoxin, extracted from colonies of the soft coral Palythoa caribaeorum, are described. There is a decrease of both membrane resting potential and overshoot during activity. Rise time of the action potential is prolonged, while repolarization is shortened. The electrical events resemble those seen with metabolic poisons."}
{"id": "PMID:21805", "title": "Peptido-aminobenzophenones--novel latentiated benzo-1,4-diazepines.", "content": "It has been shown that cleavage of the N-terminal L-amino acids of a novel series of dipeptide derivatives of 2-aminobenzophenones occurs readily in vivo to give benzo-1,4-diazepines. Such compounds may serve as useful pro-drug forms of minor tranquilizers such as Valium.", "contents": "Peptido-aminobenzophenones--novel latentiated benzo-1,4-diazepines. It has been shown that cleavage of the N-terminal L-amino acids of a novel series of dipeptide derivatives of 2-aminobenzophenones occurs readily in vivo to give benzo-1,4-diazepines. Such compounds may serve as useful pro-drug forms of minor tranquilizers such as Valium."}
{"id": "PMID:21809", "title": "[Pharmacologic peculiarities of natural and synthetic alpha-adrenomimetics].", "content": "The mechanical response of the isolated rat vas deferens to four alpha-adrenomimetic substances has been studied. The four test substances were noradrenaline, octopamine, 2-phenylethylamine and 2-(1-naphthylmethyl)imidazoline (Privin). Examination of the cumulative dose/response curves showed both qualitative and quantitative differences. Octopamine gave an alpha value (intrinsic activity) greater than that of noradrenaline; Privin proved to be a partial agonist but with affinity greater than that of noradrenaline. Various qualitative differences were also observed suggesting a possible explanation based on labilization of the membrane.", "contents": "[Pharmacologic peculiarities of natural and synthetic alpha-adrenomimetics]. The mechanical response of the isolated rat vas deferens to four alpha-adrenomimetic substances has been studied. The four test substances were noradrenaline, octopamine, 2-phenylethylamine and 2-(1-naphthylmethyl)imidazoline (Privin). Examination of the cumulative dose/response curves showed both qualitative and quantitative differences. Octopamine gave an alpha value (intrinsic activity) greater than that of noradrenaline; Privin proved to be a partial agonist but with affinity greater than that of noradrenaline. Various qualitative differences were also observed suggesting a possible explanation based on labilization of the membrane."}
{"id": "PMID:21806", "title": "[Comparison of an aceclidine tremor with arecoline and nicotine ones in rats of different ages].", "content": "A comparative characterization of a tremor produced by aceclidine (0.5--200 mg/kg), arecoline (1--30 mg/kg) and nicotine (0.1--8 mg/kg) in rats of different age is given and the influence on the tremor of atropine sulphate (1--100 mg/kg) and scopolamine hydrobromide hydrobromide (2.5 mg/kg) described. The common character of effects produced by aceclidine and arecoline was ascertained. The tremor develops in rats aged 7--8 days and its maximum duration is in rattlings of junior and medium age. M-cholino-lytics either prevent or alleviate the tremor, lacrimation and salivation induced by aceclidine or arecoline in rats of all age categories. The aceclidine model is recommended for studying the central and peripheral M-cholinergic processes in rats of various age groups.", "contents": "[Comparison of an aceclidine tremor with arecoline and nicotine ones in rats of different ages]. A comparative characterization of a tremor produced by aceclidine (0.5--200 mg/kg), arecoline (1--30 mg/kg) and nicotine (0.1--8 mg/kg) in rats of different age is given and the influence on the tremor of atropine sulphate (1--100 mg/kg) and scopolamine hydrobromide hydrobromide (2.5 mg/kg) described. The common character of effects produced by aceclidine and arecoline was ascertained. The tremor develops in rats aged 7--8 days and its maximum duration is in rattlings of junior and medium age. M-cholino-lytics either prevent or alleviate the tremor, lacrimation and salivation induced by aceclidine or arecoline in rats of all age categories. The aceclidine model is recommended for studying the central and peripheral M-cholinergic processes in rats of various age groups."}
{"id": "PMID:21807", "title": "[Mechanism of the cardiotoxic action of No-Spa].", "content": "Tests set up in vivo on rats and with an isolated spontaneously contracting atrium of the cat brought evidence that nospanum produces an adverse chronotropic action, caused by a direct effect on the cardiac pacemaker. In the rat's myocardium the drug raised the pyruvate level, increased the lactate-dehydrogenase activity and depressed that of glucose-6-phosphate-dehydrogenase. As established by differential spectrophotometry the reduced forms of pyridine-nucleotides (NAD'N, NADP'N) tend to change the nospanum spectrum. An addition of potassium chloride to an isolated atrium at the peak of the adverse chronotropic action of nospanum or an introduction of nospanum together with NAD'N abolished the cardiotropic effect of the drug. The mechanism of the cardiotoxic action of nospanum is discussed.", "contents": "[Mechanism of the cardiotoxic action of No-Spa]. Tests set up in vivo on rats and with an isolated spontaneously contracting atrium of the cat brought evidence that nospanum produces an adverse chronotropic action, caused by a direct effect on the cardiac pacemaker. In the rat's myocardium the drug raised the pyruvate level, increased the lactate-dehydrogenase activity and depressed that of glucose-6-phosphate-dehydrogenase. As established by differential spectrophotometry the reduced forms of pyridine-nucleotides (NAD'N, NADP'N) tend to change the nospanum spectrum. An addition of potassium chloride to an isolated atrium at the peak of the adverse chronotropic action of nospanum or an introduction of nospanum together with NAD'N abolished the cardiotropic effect of the drug. The mechanism of the cardiotoxic action of nospanum is discussed."}
{"id": "PMID:21808", "title": "[Effect of pharmacological agents on the development of experimental brain edema].", "content": "The effect of some neuroleptics, adreno-, sympatho- and cholinolytic substances on the development of \"traumatic\" and \"mono-iodoacetate\" brain edemas was studied in tests with rats. It was established that the neuroleptic chlorpromazine, the alpha-adreno-blocking agents phentolamine and dopegit and also the central M-cholinolytic benactizine display a marked antiedemic action in cases of \"traumatic\" edema. It is presumed that the development of the \"traumatic\" brain edema comes as a result of excitation of the alpha-adrenoreceptors in the CNS and the antiedemic action of the mentioned drugs is caused by their blocking. The development of the \"monoiodoacetate\" edema is due to disturbed cellular metabolism. The drugs under study do not prevent metabolic disorders.", "contents": "[Effect of pharmacological agents on the development of experimental brain edema]. The effect of some neuroleptics, adreno-, sympatho- and cholinolytic substances on the development of \"traumatic\" and \"mono-iodoacetate\" brain edemas was studied in tests with rats. It was established that the neuroleptic chlorpromazine, the alpha-adreno-blocking agents phentolamine and dopegit and also the central M-cholinolytic benactizine display a marked antiedemic action in cases of \"traumatic\" edema. It is presumed that the development of the \"traumatic\" brain edema comes as a result of excitation of the alpha-adrenoreceptors in the CNS and the antiedemic action of the mentioned drugs is caused by their blocking. The development of the \"monoiodoacetate\" edema is due to disturbed cellular metabolism. The drugs under study do not prevent metabolic disorders."}
{"id": "PMID:21826", "title": "Dissociation between cortisol-induced pycnosis and inhibition of [3H]uridine incorporation in rat thymocytes.", "content": "Treatment of rat thymocytes with cortisol induced an inhibition of [3H]uridine incorporation after 30-90 min, an accumulation of pycnotic cells after 90 min, and a decrease in cell viability after several hours. No cortisol-resistant cells could be distinguished, and dose-response curves for a number of glucocorticoids showed a correlation to the saturation of the glucocorticoid receptors. The pycnotic effect of cortisol increased between pH 5.2--7.0 in parallel with a stimulation of the spontaneous development of pycnotic cells. The cortisol-induced accumulation of pycnotic cells and inhibition of [3H]uridine incorporation varied independently as a function of the cell density, and in a glucose-salt medium only the pycnotic effect of cortisol became inhibited. The inhibition of [3H] uridine incorporation is therefore not an integral part of the pycnotic change of the cells. The glucocorticoid sensitivity was found to increase with the age of the animals, before the onset of thymus involution.", "contents": "Dissociation between cortisol-induced pycnosis and inhibition of [3H]uridine incorporation in rat thymocytes. Treatment of rat thymocytes with cortisol induced an inhibition of [3H]uridine incorporation after 30-90 min, an accumulation of pycnotic cells after 90 min, and a decrease in cell viability after several hours. No cortisol-resistant cells could be distinguished, and dose-response curves for a number of glucocorticoids showed a correlation to the saturation of the glucocorticoid receptors. The pycnotic effect of cortisol increased between pH 5.2--7.0 in parallel with a stimulation of the spontaneous development of pycnotic cells. The cortisol-induced accumulation of pycnotic cells and inhibition of [3H]uridine incorporation varied independently as a function of the cell density, and in a glucose-salt medium only the pycnotic effect of cortisol became inhibited. The inhibition of [3H] uridine incorporation is therefore not an integral part of the pycnotic change of the cells. The glucocorticoid sensitivity was found to increase with the age of the animals, before the onset of thymus involution."}
{"id": "PMID:21829", "title": "Estimation of serum acid proteases at pH 1.8 and pH 3.5 in patients with duodenal ulcer, gastric ulcer and gastric carcinoma.", "content": "Using a simple hemoglobin method on the basis of Anson-Mirsky's method, acid protease levels in serum were measured at pH 1.8 (pepsin) and pH 3.5 (gastricsin) in 18 healthy controls and 14 patients with duodenal ulcer, 19 patients with gastric ulcer and 18 patients with gastric cancer. Though acid protease activity in pH 1.8 in duodenal ulcer has a tendency to show a little higher level than healthy controls, there is no significant difference in acid protease levels between controls and each of three diseases.", "contents": "Estimation of serum acid proteases at pH 1.8 and pH 3.5 in patients with duodenal ulcer, gastric ulcer and gastric carcinoma. Using a simple hemoglobin method on the basis of Anson-Mirsky's method, acid protease levels in serum were measured at pH 1.8 (pepsin) and pH 3.5 (gastricsin) in 18 healthy controls and 14 patients with duodenal ulcer, 19 patients with gastric ulcer and 18 patients with gastric cancer. Though acid protease activity in pH 1.8 in duodenal ulcer has a tendency to show a little higher level than healthy controls, there is no significant difference in acid protease levels between controls and each of three diseases."}
{"id": "PMID:21830", "title": "Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage.", "content": "In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.", "contents": "Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration. All studies became abnormal at pH 6.8. At pH 6.4, assays of the intrinsic and extrinsic coaglution systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values. Platelet aggregation was reduced by more than 50%. At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished. Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH. Pepsin further enhanced platelet disaggregation. Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract. This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage."}
{"id": "PMID:21832", "title": "A genetic and biochemical analysis of the temperature sensitive, normal-winged alleles of the rudimentary locus of Drosophila melanogaster.", "content": "The genetic and biochemical characteristics of a particular class of mutants at the rudimentary locus are described. The mutants are pyrimidine auxotrophs, like classical rudimentary alleles, but they are unique in that they do not alter the size or shape of the wing (Falk and Nash 1974b). Aspartate transcarbamylase and dihydroorotase activities have been measured in seven different normal-winged mutants, and the results indicate that these strains are enzymologically \"leaky\" mutants. Previous studies have shown that three genetic functions (corresponding to the first three enzymes of pyrimidine synthesis) are associated with the rudimentary locus. Four of the seven mutants appear to affect all three of these functions. Each of the four is temperature sensitive, and a biochemical analysis of the temperature sensitivity of one of these mutants, (r)pyr1-3, suggests that a process affecting the synthesis or assembly of these enzymes is altered at high temperatures.", "contents": "A genetic and biochemical analysis of the temperature sensitive, normal-winged alleles of the rudimentary locus of Drosophila melanogaster. The genetic and biochemical characteristics of a particular class of mutants at the rudimentary locus are described. The mutants are pyrimidine auxotrophs, like classical rudimentary alleles, but they are unique in that they do not alter the size or shape of the wing (Falk and Nash 1974b). Aspartate transcarbamylase and dihydroorotase activities have been measured in seven different normal-winged mutants, and the results indicate that these strains are enzymologically \"leaky\" mutants. Previous studies have shown that three genetic functions (corresponding to the first three enzymes of pyrimidine synthesis) are associated with the rudimentary locus. Four of the seven mutants appear to affect all three of these functions. Each of the four is temperature sensitive, and a biochemical analysis of the temperature sensitivity of one of these mutants, (r)pyr1-3, suggests that a process affecting the synthesis or assembly of these enzymes is altered at high temperatures."}
{"id": "PMID:21834", "title": "[Anti-inflammatory activity of benzo(c) phenanthridine derivatives and possible mechanisms of action (author's transl)].", "content": "Of five newly synthesized benzo[c]phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I.", "contents": "[Anti-inflammatory activity of benzo(c) phenanthridine derivatives and possible mechanisms of action (author's transl)]. Of five newly synthesized benzo[c]phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I."}
{"id": "PMID:21835", "title": "[Biochemical studies of acebutolol-the beta1 specificity of acebutolol (author's transl)].", "content": "Effects of acebutolol on carbohydrate and lipid metabolism in rats and on adenylate cyclase of heart and liver in dogs were investigated to determine the beta receptor blocking properties of the compound. Acebutolol exhibited the beta blocking activity and inhibited the increase of serum lactate concentration induced by adrenaline. This inhibition was about one-sixth as potent as that of propranolol. In hyperglycemic and free fatty acid effects of adrenaline, acebutolol inhibited the adrenaline-induced free fatty acid increase more effectively than hyperglycemia induced by adrenaline. In the inhibition of stimulated adenylate cyclase activity in the heart and liver, acebutolol was more active on the heart than on liver. Relative beta1 specificity of acebutolol was 93.2. Inhibition of propranolol on adenylate cyclase activity was more potent than that of acebutolol on both tissues, but showed no specificity. These results suggest that acebutolol is beta1 selective, although its beta blocking potency is less than that of propranolol.", "contents": "[Biochemical studies of acebutolol-the beta1 specificity of acebutolol (author's transl)]. Effects of acebutolol on carbohydrate and lipid metabolism in rats and on adenylate cyclase of heart and liver in dogs were investigated to determine the beta receptor blocking properties of the compound. Acebutolol exhibited the beta blocking activity and inhibited the increase of serum lactate concentration induced by adrenaline. This inhibition was about one-sixth as potent as that of propranolol. In hyperglycemic and free fatty acid effects of adrenaline, acebutolol inhibited the adrenaline-induced free fatty acid increase more effectively than hyperglycemia induced by adrenaline. In the inhibition of stimulated adenylate cyclase activity in the heart and liver, acebutolol was more active on the heart than on liver. Relative beta1 specificity of acebutolol was 93.2. Inhibition of propranolol on adenylate cyclase activity was more potent than that of acebutolol on both tissues, but showed no specificity. These results suggest that acebutolol is beta1 selective, although its beta blocking potency is less than that of propranolol."}
{"id": "PMID:21836", "title": "[Effect of menstrual hygiene (tampons vs pads) and of the form of contraception on pH and bacterial infection of the vagina].", "content": "In menstrual hygiene vaginal tampons are preferred. Supposedly intravaginal application causes discharge. Healthy women using pads as well as tampons were examined before, during, and after menstruation. During two menstrual cycles vaginal pH was measured, bacteriological and mycological cultures were set up. The results indicated no changes of cervical-vaginal-secretion, nor was the pH changed. Taking the used contraceptive method into consideration, we found that intrauterine devices and oral contraceptives caused most of bacterial discharge and the expected shifting to alcaline pH. No increase of vaginal fungus was noted. The use of intravaginal tampons for menstrual bleeding therefore had no ill effects.", "contents": "[Effect of menstrual hygiene (tampons vs pads) and of the form of contraception on pH and bacterial infection of the vagina]. In menstrual hygiene vaginal tampons are preferred. Supposedly intravaginal application causes discharge. Healthy women using pads as well as tampons were examined before, during, and after menstruation. During two menstrual cycles vaginal pH was measured, bacteriological and mycological cultures were set up. The results indicated no changes of cervical-vaginal-secretion, nor was the pH changed. Taking the used contraceptive method into consideration, we found that intrauterine devices and oral contraceptives caused most of bacterial discharge and the expected shifting to alcaline pH. No increase of vaginal fungus was noted. The use of intravaginal tampons for menstrual bleeding therefore had no ill effects."}
{"id": "PMID:21837", "title": "[Length of effectiveness of calcium-containing and calcium-free antacids. A double-blind study].", "content": "The effect of a Ca-containing and Ca-free antacid on meal-stimulated acid secretion was examined by intragastric titration with pH being measured extragastrically. The Ca-containing antacid was more effective in neutralisation of the intragastric content (pH greater than 5,8) and increasing the pH (p less than 0,002). The acid secretion was reduced (p less than 0,04) by the Ca-free antacid and remained constant after administration of the Ca-containing antacid. There were no significant differences between acid secretion before and after the administration of the Ca-free and the Ca-containing antacid.", "contents": "[Length of effectiveness of calcium-containing and calcium-free antacids. A double-blind study]. The effect of a Ca-containing and Ca-free antacid on meal-stimulated acid secretion was examined by intragastric titration with pH being measured extragastrically. The Ca-containing antacid was more effective in neutralisation of the intragastric content (pH greater than 5,8) and increasing the pH (p less than 0,002). The acid secretion was reduced (p less than 0,04) by the Ca-free antacid and remained constant after administration of the Ca-containing antacid. There were no significant differences between acid secretion before and after the administration of the Ca-free and the Ca-containing antacid."}
{"id": "PMID:21840", "title": "Liver enzyme adaptation after lithium administration in handled and nonhandled rats.", "content": "We have examined the interaction of lithium administration and the infant stimulation procedure of handling on hormonally regulated enzymes of liver. Animals handled in infancy show an increased morning corticosterone level in response to lithium feeding and markedly elevated serum glucose during refeeding following a two day fast, when compared to non-handled control animals. Lithium alters serum corticosterone both in response to the stress of fasting, and during the diurnal cycle following glucose refeeding. The handled and non-handled animals respond differently. These results are consistent with previously reported alterations in feedback regulation of ACTH secretion in handled animals. They also indicate a further modification of this system in response to lithium administration.", "contents": "Liver enzyme adaptation after lithium administration in handled and nonhandled rats. We have examined the interaction of lithium administration and the infant stimulation procedure of handling on hormonally regulated enzymes of liver. Animals handled in infancy show an increased morning corticosterone level in response to lithium feeding and markedly elevated serum glucose during refeeding following a two day fast, when compared to non-handled control animals. Lithium alters serum corticosterone both in response to the stress of fasting, and during the diurnal cycle following glucose refeeding. The handled and non-handled animals respond differently. These results are consistent with previously reported alterations in feedback regulation of ACTH secretion in handled animals. They also indicate a further modification of this system in response to lithium administration."}
{"id": "PMID:21842", "title": "Conformational changes induced by ionic strength and pH in two bovine myelin basic proteins.", "content": "The structures of two biologically different myelin proteins, A1 from the central nervous system and P2 from the peripheral nervous system, were investigated. Both proteins were isolated from nerve tissues. Conformational changes in the homogeneous proteins were examined in aqueous solutions by means of circular dichroism measurements. The secondary structures of both proteins proved to be very stable between pH 2.5 and pH 11.7. Unlike the P2 protein, the A1 protein is stable up to pH 13 without detectable conformational changes. The stereochemistry of the polypeptide chains of both proteins is markedly different in the presence of urea. While the value of theta222 for the A1 protein changes linearly with increasing urea concentration, a sigmoidal curve was obtained for the P2 protein. The observed differences in the dichroic properties of the basic myelin proteins A1 and P2 indicate the possibility of further structure - function correlations.", "contents": "Conformational changes induced by ionic strength and pH in two bovine myelin basic proteins. The structures of two biologically different myelin proteins, A1 from the central nervous system and P2 from the peripheral nervous system, were investigated. Both proteins were isolated from nerve tissues. Conformational changes in the homogeneous proteins were examined in aqueous solutions by means of circular dichroism measurements. The secondary structures of both proteins proved to be very stable between pH 2.5 and pH 11.7. Unlike the P2 protein, the A1 protein is stable up to pH 13 without detectable conformational changes. The stereochemistry of the polypeptide chains of both proteins is markedly different in the presence of urea. While the value of theta222 for the A1 protein changes linearly with increasing urea concentration, a sigmoidal curve was obtained for the P2 protein. The observed differences in the dichroic properties of the basic myelin proteins A1 and P2 indicate the possibility of further structure - function correlations."}
{"id": "PMID:21843", "title": "Amino acid sequence of toxin III from Anemonia sulcata.", "content": "Toxin III, the smallest toxin component of the poison of the sea anemone Anemonia sulcata, is a polypeptide with 27 amino acids. Its structure is stabilized by three disulfide bridges. The amino acid sequence was determined by solid-phase Edman degradation of the aminoethylated derivative. The peptide was coupled to the carrier, porous glass, by thiourea bridges between the alpha-amino group of arginine-1 and the epsilon-amino group of lysine-26 and the isothiocyanate groups of the carrier. Another fraction of the polypeptide was bound by an acid-amide condensation of the C-terminal valine-27 with the aminopropyl group of the carrier. The sequence of toxin III has no regions homologous to the 47-residue toxin II. Comparison with the known partial sequence of toxin I, which contains 46 amino acids (Wunderer, G. & Eulitz, M., in preparation) also fails to reveal homologies.", "contents": "Amino acid sequence of toxin III from Anemonia sulcata. Toxin III, the smallest toxin component of the poison of the sea anemone Anemonia sulcata, is a polypeptide with 27 amino acids. Its structure is stabilized by three disulfide bridges. The amino acid sequence was determined by solid-phase Edman degradation of the aminoethylated derivative. The peptide was coupled to the carrier, porous glass, by thiourea bridges between the alpha-amino group of arginine-1 and the epsilon-amino group of lysine-26 and the isothiocyanate groups of the carrier. Another fraction of the polypeptide was bound by an acid-amide condensation of the C-terminal valine-27 with the aminopropyl group of the carrier. The sequence of toxin III has no regions homologous to the 47-residue toxin II. Comparison with the known partial sequence of toxin I, which contains 46 amino acids (Wunderer, G. & Eulitz, M., in preparation) also fails to reveal homologies."}
{"id": "PMID:21844", "title": "Hemocyanins in spiders, IV[1]. Subunit heterogeneity of Eurypelma (Dugesiella) hemocyanin, and separation of polypeptide chains.", "content": "The hemocyanin of the North American tarantula Eurypelma californicum (Dugesiella californica) is dissociated at pH 9.6 into monomers (Mr about 70 000) and dimers (Mr about 140 000), which were separated by gel filtration. The monomer peak was resolved by preparative polyacrylamide gel electrophoresis and yielded 4 protein bands, three of which (1, 3 and 4M) are apparently homogeneous. Band 2 contains two sub-fractions (2I and 2II). The dimer peak contains two dimers (bands 4D and 5). Upon treatment with 5mM cysteine the dimer band 5 is dissociated, yielding only one type of monomer identical with band 3. The other dimer, which was only partially dissociated by 10mM EDTA, is most probably a heterodimer, one component being electrophoretically indistinguishable from band 2II. After treatment of the native hemocyanin with sodium dodecylsulfate and analysis in gradient gel slabs, 6 polypeptide chains were observed (labeled a - f). They correspond to the products of alkaline dissociation as follows: band 1 = e, band 2I = a, band 2II = c, band 3 = f, band 4M = d, band 4D = b plus c, band 5 = f. The molecular weights were determined by dodecylsulfate gel electrophoresis in gradient gels, and by sedimentation equilibrium analysis and found to range between 67 000 and 76 000. The sedimentation coefficients are between 4.4 and 4.7 S for the monomers and 6.6 and 6.7 for the dimers. The isoelectric points range from pH 4.5 to pH 5.4. The findings are discussed with respect to the limitations of molecular weight determination by conventional dodecylsulfate gel electrophoresis, to the structure of the hemocyanin oligomers and to possible biological significance.", "contents": "Hemocyanins in spiders, IV[1]. Subunit heterogeneity of Eurypelma (Dugesiella) hemocyanin, and separation of polypeptide chains. The hemocyanin of the North American tarantula Eurypelma californicum (Dugesiella californica) is dissociated at pH 9.6 into monomers (Mr about 70 000) and dimers (Mr about 140 000), which were separated by gel filtration. The monomer peak was resolved by preparative polyacrylamide gel electrophoresis and yielded 4 protein bands, three of which (1, 3 and 4M) are apparently homogeneous. Band 2 contains two sub-fractions (2I and 2II). The dimer peak contains two dimers (bands 4D and 5). Upon treatment with 5mM cysteine the dimer band 5 is dissociated, yielding only one type of monomer identical with band 3. The other dimer, which was only partially dissociated by 10mM EDTA, is most probably a heterodimer, one component being electrophoretically indistinguishable from band 2II. After treatment of the native hemocyanin with sodium dodecylsulfate and analysis in gradient gel slabs, 6 polypeptide chains were observed (labeled a - f). They correspond to the products of alkaline dissociation as follows: band 1 = e, band 2I = a, band 2II = c, band 3 = f, band 4M = d, band 4D = b plus c, band 5 = f. The molecular weights were determined by dodecylsulfate gel electrophoresis in gradient gels, and by sedimentation equilibrium analysis and found to range between 67 000 and 76 000. The sedimentation coefficients are between 4.4 and 4.7 S for the monomers and 6.6 and 6.7 for the dimers. The isoelectric points range from pH 4.5 to pH 5.4. The findings are discussed with respect to the limitations of molecular weight determination by conventional dodecylsulfate gel electrophoresis, to the structure of the hemocyanin oligomers and to possible biological significance."}
{"id": "PMID:21849", "title": "Opsonic requirements for phagocytosis of Streptococcus pneumoniae types VI, XVIII, XXIII, and XXV.", "content": "An assay system employing radiolabeled, heat-killed Streptococcus pneumoniae and human polymorphonuclear leukocytes was utilized to study serum pneumococcal opsonic requirements. Comparing the kinetics of phagocytosis in normal serum, heat-inactivated serum, immunoglobulin G (IgG)-deficient serum, C2-deficient serum, and magnesium dichloride ethyleneglycol-tetraacetic acid (MgEGTA)-chelated serum allowed definition of the opsonic requirements for four pneumococcal serotypes: VI XVIII, XXIII, and XXV. All four serotypes were efficiently opsonized in 10% normal serum. Only type XVIII was opsonized in heat-inactivated serum. All four were also opsonized in IgG-deficient serum but not as efficiently as in normal serum. Opsonization via the alternative pathway was diminished for all four serotypes in 10% MgEGTA-chelated and C2-deficient serum. Furthermore, by varying the concentration of MgEGTA-chelated serum, it was found that type XXV was least efficiently opsonized via the alternative pathway. The quantitative nature of this assay system will permit measurement of bacterial and host factors that may contribute to host susceptibility to pneumococcal infection.", "contents": "Opsonic requirements for phagocytosis of Streptococcus pneumoniae types VI, XVIII, XXIII, and XXV. An assay system employing radiolabeled, heat-killed Streptococcus pneumoniae and human polymorphonuclear leukocytes was utilized to study serum pneumococcal opsonic requirements. Comparing the kinetics of phagocytosis in normal serum, heat-inactivated serum, immunoglobulin G (IgG)-deficient serum, C2-deficient serum, and magnesium dichloride ethyleneglycol-tetraacetic acid (MgEGTA)-chelated serum allowed definition of the opsonic requirements for four pneumococcal serotypes: VI XVIII, XXIII, and XXV. All four serotypes were efficiently opsonized in 10% normal serum. Only type XVIII was opsonized in heat-inactivated serum. All four were also opsonized in IgG-deficient serum but not as efficiently as in normal serum. Opsonization via the alternative pathway was diminished for all four serotypes in 10% MgEGTA-chelated and C2-deficient serum. Furthermore, by varying the concentration of MgEGTA-chelated serum, it was found that type XXV was least efficiently opsonized via the alternative pathway. The quantitative nature of this assay system will permit measurement of bacterial and host factors that may contribute to host susceptibility to pneumococcal infection."}
{"id": "PMID:21850", "title": "Rabbit intestinal fluid stimulation by an enterotoxigenic factor of Staphylococcus aureus.", "content": "An exoprotein of Staphylococcus aureus 100 that elicited a positive ileal loop response in the rabbit model was investigated in this study. The protein, as it occurred in the culture supernatant fluid, could be detected initially in the late log phase of growth under aerobic and anaerobic conditions. It was stable under acidic conditions to pH 2.0 after 24 h at 4 degrees C. Thirty-minute treatments at 80 degrees C destroyed the ileal loop activity whereas similar trials at 70 degrees C had no effect. Although preparations of staphylococcal enterotoxins purified by other investigators did not produce positive ileal loops, the enterotoxigenic activity of the S. aureus 100 supernatant fluid could be neutralized by antisera prepared against enterotoxins A and B. Throughout purification studies, the active moiety reacted serologically with antiserum A. Polyacrylamide gel electrophoresis of the partially purified protein produced migration patterns nearly identical to those of enterotoxin A.", "contents": "Rabbit intestinal fluid stimulation by an enterotoxigenic factor of Staphylococcus aureus. An exoprotein of Staphylococcus aureus 100 that elicited a positive ileal loop response in the rabbit model was investigated in this study. The protein, as it occurred in the culture supernatant fluid, could be detected initially in the late log phase of growth under aerobic and anaerobic conditions. It was stable under acidic conditions to pH 2.0 after 24 h at 4 degrees C. Thirty-minute treatments at 80 degrees C destroyed the ileal loop activity whereas similar trials at 70 degrees C had no effect. Although preparations of staphylococcal enterotoxins purified by other investigators did not produce positive ileal loops, the enterotoxigenic activity of the S. aureus 100 supernatant fluid could be neutralized by antisera prepared against enterotoxins A and B. Throughout purification studies, the active moiety reacted serologically with antiserum A. Polyacrylamide gel electrophoresis of the partially purified protein produced migration patterns nearly identical to those of enterotoxin A."}
{"id": "PMID:21851", "title": "Factors affecting germination of Trichophyton mentagrophytes arthrospores.", "content": "Nutritional and environmental factors affecting germination of Trichophyton mentagrophytes arthrospores were investigated. Germination of dormant arthrospores occurred only in rich complex media such as Sabouraud dextrose broth or vitamin-free Casamino Acids. However, once activated, arthrospores were able to germinate under wide ranges of pH (5.5 to 8.0, optimal 6.5) and temperature (20 to 39 degrees C, optimal 37 degrees C) in the presence of certain single amino acids or oligopeptides known to be present in the human cutaneous tissues. Dormant arthrospores could be activated by incubation in distilled water at 25 degrees C for 24 h or by brief exposure to sublethal doses of heat (45 degrees C for 10 to 20 min). Approximately 20% of activated arthrospores underwent spontaneous germination at 37 degrees C during an additional 18 h of incubation in distilled water. All monosaccharides, purines, pyrimidines, and nucleosides tested failed to induce germination of T. mentagrophytes arthrospores. Germination rate was affected by the concentration of germination inducers as well as that of arthrospores. The germination process of T. mentagrophytes arthrospores was found to be oxygen dependent and was relatively tolerant to NaCl, clotrimazole, cycloheximide, griseofulvin, and tolnaftate.", "contents": "Factors affecting germination of Trichophyton mentagrophytes arthrospores. Nutritional and environmental factors affecting germination of Trichophyton mentagrophytes arthrospores were investigated. Germination of dormant arthrospores occurred only in rich complex media such as Sabouraud dextrose broth or vitamin-free Casamino Acids. However, once activated, arthrospores were able to germinate under wide ranges of pH (5.5 to 8.0, optimal 6.5) and temperature (20 to 39 degrees C, optimal 37 degrees C) in the presence of certain single amino acids or oligopeptides known to be present in the human cutaneous tissues. Dormant arthrospores could be activated by incubation in distilled water at 25 degrees C for 24 h or by brief exposure to sublethal doses of heat (45 degrees C for 10 to 20 min). Approximately 20% of activated arthrospores underwent spontaneous germination at 37 degrees C during an additional 18 h of incubation in distilled water. All monosaccharides, purines, pyrimidines, and nucleosides tested failed to induce germination of T. mentagrophytes arthrospores. Germination rate was affected by the concentration of germination inducers as well as that of arthrospores. The germination process of T. mentagrophytes arthrospores was found to be oxygen dependent and was relatively tolerant to NaCl, clotrimazole, cycloheximide, griseofulvin, and tolnaftate."}
{"id": "PMID:21852", "title": "International aspects of oral microbiology.", "content": "It appears that the bacteria of the mouth are remarkably similar throughout the world. There are differences, but they are mostly of a quantitative rather than a qualitative nature. Although much is yet to be learned on the regulation of the oral ecosystems, these quantitative fluctuations to a large extent seem to be induced by different dietary patterns: the food exerting a strong selective pressure on the oral microbiota.", "contents": "International aspects of oral microbiology. It appears that the bacteria of the mouth are remarkably similar throughout the world. There are differences, but they are mostly of a quantitative rather than a qualitative nature. Although much is yet to be learned on the regulation of the oral ecosystems, these quantitative fluctuations to a large extent seem to be induced by different dietary patterns: the food exerting a strong selective pressure on the oral microbiota."}
{"id": "PMID:21853", "title": "Classification and determination of cerebral biovailability of psychotropic drugs by quantitative \"pharmaco-EEG\" and psychometric investigations (studies with AX-A411-BS).", "content": "Utilizing computerized quantitative analysis of the human scalp recorded electroencephalogram (EEG), it is possible to classify psychotropic drugs. While neuroleptic compounds produce an increase of slow and decrease of fast activities, anxiolytic substances induce an augmentation of fast waves, decrease of alpha waves and--according to the sedative properties of the drug--an increase or decrease of slow waves. Antidepressants produce a concomitant augmentation of slow and fast activities as well as an attenuation of alpha waves. Nootropic substances attenuate slow activities, augment alpha and slow beta waves and decrease fast beta waves. The latter alterations are quite opposite to age-related changes. Since the main psychopharmacological classes seem to have characteristic pharmaco-EEG profiles, the method proved to be useful for determination of psychoactivity and cerebral bioavailability of newly developed substances as for instance AX-A411-BS, a new benzodiazepine. The latter substance was found to be CNS-active and was classified as anxiolytic. It induced dosedependent changes, which were barely visible in the 2nd hour post-drug, became quite obvious in the 4th hour and increased until the 8th hour after oral administration of one single dose. In the higher dosage range, slow activities came to the fore, indicating aoditional sedative properties. Psychometric tests measuring attention, psychomotor activity. mood, vigilance, extroversion, concentration aith a long-lasting effect. The implications of these methods are discussed.", "contents": "Classification and determination of cerebral biovailability of psychotropic drugs by quantitative \"pharmaco-EEG\" and psychometric investigations (studies with AX-A411-BS). Utilizing computerized quantitative analysis of the human scalp recorded electroencephalogram (EEG), it is possible to classify psychotropic drugs. While neuroleptic compounds produce an increase of slow and decrease of fast activities, anxiolytic substances induce an augmentation of fast waves, decrease of alpha waves and--according to the sedative properties of the drug--an increase or decrease of slow waves. Antidepressants produce a concomitant augmentation of slow and fast activities as well as an attenuation of alpha waves. Nootropic substances attenuate slow activities, augment alpha and slow beta waves and decrease fast beta waves. The latter alterations are quite opposite to age-related changes. Since the main psychopharmacological classes seem to have characteristic pharmaco-EEG profiles, the method proved to be useful for determination of psychoactivity and cerebral bioavailability of newly developed substances as for instance AX-A411-BS, a new benzodiazepine. The latter substance was found to be CNS-active and was classified as anxiolytic. It induced dosedependent changes, which were barely visible in the 2nd hour post-drug, became quite obvious in the 4th hour and increased until the 8th hour after oral administration of one single dose. In the higher dosage range, slow activities came to the fore, indicating aoditional sedative properties. Psychometric tests measuring attention, psychomotor activity. mood, vigilance, extroversion, concentration aith a long-lasting effect. The implications of these methods are discussed."}
{"id": "PMID:21854", "title": "On the distribution of drugs in saliva and blood plasma.", "content": "The equilibration of drug concentrations between blood plasma (unbound part) and saliva was studied for selected drugs with different physicochemical properties: Quinidine, sulfamerazine, paracetamol, diazepam and ethanol. From these and other experimental results it is suggested: 1. The concentration ratio between saliva and blood plasma (unbound) can only equal one for basic drugs with a pK a lower than 5.5 and acid drugs with a pK a higher than 8.5 and for pH indifferent drugs. 2. The drug must have a sufficient permeation ability through lipid membranes, valuable by the lipid water partition coefficient.", "contents": "On the distribution of drugs in saliva and blood plasma. The equilibration of drug concentrations between blood plasma (unbound part) and saliva was studied for selected drugs with different physicochemical properties: Quinidine, sulfamerazine, paracetamol, diazepam and ethanol. From these and other experimental results it is suggested: 1. The concentration ratio between saliva and blood plasma (unbound) can only equal one for basic drugs with a pK a lower than 5.5 and acid drugs with a pK a higher than 8.5 and for pH indifferent drugs. 2. The drug must have a sufficient permeation ability through lipid membranes, valuable by the lipid water partition coefficient."}
{"id": "PMID:21866", "title": "Consumer survey: an approach to teaching consumer participation in community health.", "content": "This consumer survey conducted by senior baccalaureate students in a family and community nursing course developed as a result of student recognition of the need for direct consumer input in identification of community health needs. The format was developed, pretested and revised by faculty. The door-to-door survey was carried out by pairs of students during clinical time over a six-week period. Through a written summary of the experience and class discussion students indicated an increased awareness of the community as a dynamic reality and a heightened awareness of their caseload families' relationships to the community. Students also demonstrated an appreciation for consumer representation in health planning and for some of the strengths and weaknesses of surveying as a method for consumer involvement.", "contents": "Consumer survey: an approach to teaching consumer participation in community health. This consumer survey conducted by senior baccalaureate students in a family and community nursing course developed as a result of student recognition of the need for direct consumer input in identification of community health needs. The format was developed, pretested and revised by faculty. The door-to-door survey was carried out by pairs of students during clinical time over a six-week period. Through a written summary of the experience and class discussion students indicated an increased awareness of the community as a dynamic reality and a heightened awareness of their caseload families' relationships to the community. Students also demonstrated an appreciation for consumer representation in health planning and for some of the strengths and weaknesses of surveying as a method for consumer involvement."}
{"id": "PMID:21867", "title": "An evalutive study of a nursing center for community health nursing student experiences.", "content": "The findings from the evaluation study indicated that nursing students were able to accomplish the community health nursing course objectives through a non-traditional entry point. The study also demonstrated that a School of Nursing can successfully initiate and carry out health care (the service program was also evaluated) and that students, challenged and integrated into such efforts can become extremely useful as a resource to the community while simultaneously contributing to their own learning and professional development. The Nursing Services Center approach (nursing clinic that also offers home care) has been able to serve some of the preventive health needs of a population while at the same time providing students with educational experience in the field.", "contents": "An evalutive study of a nursing center for community health nursing student experiences. The findings from the evaluation study indicated that nursing students were able to accomplish the community health nursing course objectives through a non-traditional entry point. The study also demonstrated that a School of Nursing can successfully initiate and carry out health care (the service program was also evaluated) and that students, challenged and integrated into such efforts can become extremely useful as a resource to the community while simultaneously contributing to their own learning and professional development. The Nursing Services Center approach (nursing clinic that also offers home care) has been able to serve some of the preventive health needs of a population while at the same time providing students with educational experience in the field."}
{"id": "PMID:21868", "title": "Physiologic measures of nonhuman primates during physical restraint and chemical immobilization.", "content": "The arterial acid-base balance and other selected physiologic measures of physically restrained and chemically immobilized nonhuman primates from the families Callithricidae, Cebidae, Cercopithecidae, and Pongidae were compared. The physically restrained primates had significantly lower pH, pCO2, and base excess values, but they had significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Of 56 physically restrained primates, 30 (54%) experienced severe metabolic acidosis, with pH values less than 7.2; 15 (27% of total) had pH values less than 7.1. Two types of behavior were observed during the physical restraint of golden marmosets. Some of the marmosets were excited during restraint, with a great deal of struggling and vocalizing. The other marmosets were quiet and calm, with minimal struggling. The excited group had significantly lower pH, pCO2, and base excess values, but significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Primates immobilized with ketamine or tiletaminezolazepam had a near normal acid-base balance and were handled more easily than the physically restrained animals.", "contents": "Physiologic measures of nonhuman primates during physical restraint and chemical immobilization. The arterial acid-base balance and other selected physiologic measures of physically restrained and chemically immobilized nonhuman primates from the families Callithricidae, Cebidae, Cercopithecidae, and Pongidae were compared. The physically restrained primates had significantly lower pH, pCO2, and base excess values, but they had significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Of 56 physically restrained primates, 30 (54%) experienced severe metabolic acidosis, with pH values less than 7.2; 15 (27% of total) had pH values less than 7.1. Two types of behavior were observed during the physical restraint of golden marmosets. Some of the marmosets were excited during restraint, with a great deal of struggling and vocalizing. The other marmosets were quiet and calm, with minimal struggling. The excited group had significantly lower pH, pCO2, and base excess values, but significantly higher pO2 values, rectal temperatures, and pulse and respiration rates. Primates immobilized with ketamine or tiletaminezolazepam had a near normal acid-base balance and were handled more easily than the physically restrained animals."}
{"id": "PMID:21872", "title": "Isolation and preliminary characterization of two forms of ribulose 1,5-bisphosphate carboxylase from Rhodopseudomonas capsulata.", "content": "The presence of two distinct forms of ribulose 1,5-bisphosphate carboxylase has been demonstrated in extracts of Rhodopseudomonas capsulata, similar to the form I (peak I) and form II (peak II) carboxylases previously described from R. sphaeroides (J. Gibson and F. R. Tabita, J. Biol. Chem 252:943-949, 1977). The two activities, separated by diethylaminoethyl-cellulose chromatography, were shown to be of different molecular size after assay on polyacrylamide gels. The higher-molecular-weight carboxylase from R. capsulata was designated form I-C, whereas the smaller enzyme was designated form II-C. Catalytic studies revealed significant differences between the two enzymes in response to pH and the effector 6-phosphogluconate. Immunological studies with antisera directed against the carboxylases from R. sphaeroides demonstrated antigenic differences between the two R. capsulata enzymes; cross-reactivity was observed only between R. sphaeroides anti-form II serum and the corresponding R. capsulata enzyme, form II-C.", "contents": "Isolation and preliminary characterization of two forms of ribulose 1,5-bisphosphate carboxylase from Rhodopseudomonas capsulata. The presence of two distinct forms of ribulose 1,5-bisphosphate carboxylase has been demonstrated in extracts of Rhodopseudomonas capsulata, similar to the form I (peak I) and form II (peak II) carboxylases previously described from R. sphaeroides (J. Gibson and F. R. Tabita, J. Biol. Chem 252:943-949, 1977). The two activities, separated by diethylaminoethyl-cellulose chromatography, were shown to be of different molecular size after assay on polyacrylamide gels. The higher-molecular-weight carboxylase from R. capsulata was designated form I-C, whereas the smaller enzyme was designated form II-C. Catalytic studies revealed significant differences between the two enzymes in response to pH and the effector 6-phosphogluconate. Immunological studies with antisera directed against the carboxylases from R. sphaeroides demonstrated antigenic differences between the two R. capsulata enzymes; cross-reactivity was observed only between R. sphaeroides anti-form II serum and the corresponding R. capsulata enzyme, form II-C."}
{"id": "PMID:21873", "title": "Thermodynamics of the electrochemical proton gradient in bovine heart submitochondrial particles.", "content": "The electrical and chemical components of the electrochemical proton gradient of submitochondrial particles can be monitored simultaneously by continuously recording optical signals from the probes oxonol-VI and 9-aminoacridine. Either respiration or ATP hydrolysis causes a red shift in the absorption spectrum of oxonol-VI indicative of a membrane potential and a decrease of the fluorescence of 9-aminoacridine indicative of a pH gradient. The magnitude of the membrane potential and pH gradient formed by respiring submitochondrial particles can be modulated by the thermodynamic phosphorylation potential (deltaGp) of the adenine nucleotide system. deltaGp is the Gibbs free energy of ATP synthesis and is defined by the relationship deltaGp = -deltaG'o + RTln([ATP]/[ADP][Pi] where deltaG'o is the standard free energy of ATP hydrolysis. Increasing values of deltaGp cause an increase in the steady state magnitudes of both the membrane potential and pH gradient. Thermodynamic phosphorylation potential titration experiments indicate that the electrochemical proton gradient normally maintained by respiring submitochondrial particles has an energy equivalent to 10.5 to 10.9 kcal/mol.", "contents": "Thermodynamics of the electrochemical proton gradient in bovine heart submitochondrial particles. The electrical and chemical components of the electrochemical proton gradient of submitochondrial particles can be monitored simultaneously by continuously recording optical signals from the probes oxonol-VI and 9-aminoacridine. Either respiration or ATP hydrolysis causes a red shift in the absorption spectrum of oxonol-VI indicative of a membrane potential and a decrease of the fluorescence of 9-aminoacridine indicative of a pH gradient. The magnitude of the membrane potential and pH gradient formed by respiring submitochondrial particles can be modulated by the thermodynamic phosphorylation potential (deltaGp) of the adenine nucleotide system. deltaGp is the Gibbs free energy of ATP synthesis and is defined by the relationship deltaGp = -deltaG'o + RTln([ATP]/[ADP][Pi] where deltaG'o is the standard free energy of ATP hydrolysis. Increasing values of deltaGp cause an increase in the steady state magnitudes of both the membrane potential and pH gradient. Thermodynamic phosphorylation potential titration experiments indicate that the electrochemical proton gradient normally maintained by respiring submitochondrial particles has an energy equivalent to 10.5 to 10.9 kcal/mol."}
{"id": "PMID:21874", "title": "Singlet oxygen as a mediator in the hematoporphyrin-catalyzed photooxidation of NADPH to NADP+ in deuterium oxide.", "content": "The oxygen-dependent photooxidation of NADPH in the presence of hematoporphyrin in D2O results in the production of enzymatically active NADP+. The reaction is not inhibited by benzoate, mannitol, superoxide dismutase, or catalase. Moreover, addition of either potassium superoxide or H2O2 does not potentiate the reaction. This suggests OH-, H2O2, and O-2 are not likely to be the reactive oxygen species in this system. The oxidation is inhibited by various singlet oxygen quenchers and inhibitors such as 1,4-diazabicyclo[2.2.2]octane, 2,5-dimethylfuran plus methanol, histidine, and methionine. In addition, the rate of oxidation in H2O is less than one-fifth of that in D2O. The results suggest a singlet oxygen-mediated process. During the oxidation, no superoxide radical production could be detected with either ferricytochrome c or nitroblue tetrazolium. However, H2O2 has been found as one of the products. These observations are consistent with an oxidation-reduction reaction between singlet oxygen and NADPH to form H2O2 and NADP+, catalyzed by the light-activated photosensitizer hematoporphyrin.", "contents": "Singlet oxygen as a mediator in the hematoporphyrin-catalyzed photooxidation of NADPH to NADP+ in deuterium oxide. The oxygen-dependent photooxidation of NADPH in the presence of hematoporphyrin in D2O results in the production of enzymatically active NADP+. The reaction is not inhibited by benzoate, mannitol, superoxide dismutase, or catalase. Moreover, addition of either potassium superoxide or H2O2 does not potentiate the reaction. This suggests OH-, H2O2, and O-2 are not likely to be the reactive oxygen species in this system. The oxidation is inhibited by various singlet oxygen quenchers and inhibitors such as 1,4-diazabicyclo[2.2.2]octane, 2,5-dimethylfuran plus methanol, histidine, and methionine. In addition, the rate of oxidation in H2O is less than one-fifth of that in D2O. The results suggest a singlet oxygen-mediated process. During the oxidation, no superoxide radical production could be detected with either ferricytochrome c or nitroblue tetrazolium. However, H2O2 has been found as one of the products. These observations are consistent with an oxidation-reduction reaction between singlet oxygen and NADPH to form H2O2 and NADP+, catalyzed by the light-activated photosensitizer hematoporphyrin."}
{"id": "PMID:21875", "title": "Metabolism of dog gastric mucosa. Levels of glycolytic, citric acid cycle and other intermediates.", "content": "Several metabolites, including those of glycolysis, the citric acid cycle, the hexose monophosphate shunt, glutamate, aspartate, and Coenzyme A were measured in defined parietal cell-enriched freeze-dried sections of dog gastric biopsies derived from nonsecreting and secreting tissue. In addition, NH3, ribulose 5-phosphate, glycerol, and succinate were measured in perchloric acid extracts of biopsies. The onset of secretion increased the level of glycolytic intermediates including pyruvate and lactate with the most marked increase being in fructose 1,6-diphosphate levels. The level of 6-phosphogluconate and ribulose 5-phosphate also increased, in spite of a constant NADP+/NADPH ratio. The levels of all the citric acid cycle intermediates measured also rose, the most marked rise being in malate and fumarate. The levels of glycerol, acetyl-CoA, and CoA increased, but the ratio of the latter intermediates remained constant. Calculation of the ratio of the oxidized to reduced form of diphosphopyridine nucleotide indicated a fall of the ratio in the cytoplasm and a rise in the mitochondria. From these data, it is concluded that the major energy source for acid secretion is due to an increase in citric acid cycle activity and that glycolysis, and probably also fatty acid oxidation, is stimulated to provide mitochondrial substrate.", "contents": "Metabolism of dog gastric mucosa. Levels of glycolytic, citric acid cycle and other intermediates. Several metabolites, including those of glycolysis, the citric acid cycle, the hexose monophosphate shunt, glutamate, aspartate, and Coenzyme A were measured in defined parietal cell-enriched freeze-dried sections of dog gastric biopsies derived from nonsecreting and secreting tissue. In addition, NH3, ribulose 5-phosphate, glycerol, and succinate were measured in perchloric acid extracts of biopsies. The onset of secretion increased the level of glycolytic intermediates including pyruvate and lactate with the most marked increase being in fructose 1,6-diphosphate levels. The level of 6-phosphogluconate and ribulose 5-phosphate also increased, in spite of a constant NADP+/NADPH ratio. The levels of all the citric acid cycle intermediates measured also rose, the most marked rise being in malate and fumarate. The levels of glycerol, acetyl-CoA, and CoA increased, but the ratio of the latter intermediates remained constant. Calculation of the ratio of the oxidized to reduced form of diphosphopyridine nucleotide indicated a fall of the ratio in the cytoplasm and a rise in the mitochondria. From these data, it is concluded that the major energy source for acid secretion is due to an increase in citric acid cycle activity and that glycolysis, and probably also fatty acid oxidation, is stimulated to provide mitochondrial substrate."}
{"id": "PMID:21877", "title": "Purification and properties of an endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae.", "content": "An enzyme that hydrolyzes the O-glycosidic linkage between alpha-N-acetyl-D-galactosamine and serine or threonine in mucins and mucin-type glycoproteins was purified by chromatography on an Affi-Gel 202 column or isoelectric focusing from filtrates of Diplococcus pneumoniae cultures. The final preparations were free of protease and a wide range of other glycosidase activities. The preparation obtained by isoelectric focusing was shown to consist of a single protein by gel filtration and sodium dodecyl sulfate-gel electrophoresis. This preparation had an apparent molecular weight of about 160,000, determined by gel filtration, an optimum pH of 7.6, and an isoelectric point in the range pH 8 to 9. The enzyme releases the disaccharide Gal-GalNAc from a variety of glycopeptide and glycoprotein substrates and appears to have a specific requirement for an unsubstituted galactose in the nonreducing terminus and an alpha linkage between N-acetylgalactosamine and the aglycone. This is the only endoenzyme known capable of cleaving the linkage between a carbohydrate and serine or threonine residues in glycoproteins. The ability of this enzyme to act on macromolecular substrates and its pH optimum makes it ideally suited to explore the distribution and function of mucin-type glycoproteins on normal and cancer cell surfaces.", "contents": "Purification and properties of an endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae. An enzyme that hydrolyzes the O-glycosidic linkage between alpha-N-acetyl-D-galactosamine and serine or threonine in mucins and mucin-type glycoproteins was purified by chromatography on an Affi-Gel 202 column or isoelectric focusing from filtrates of Diplococcus pneumoniae cultures. The final preparations were free of protease and a wide range of other glycosidase activities. The preparation obtained by isoelectric focusing was shown to consist of a single protein by gel filtration and sodium dodecyl sulfate-gel electrophoresis. This preparation had an apparent molecular weight of about 160,000, determined by gel filtration, an optimum pH of 7.6, and an isoelectric point in the range pH 8 to 9. The enzyme releases the disaccharide Gal-GalNAc from a variety of glycopeptide and glycoprotein substrates and appears to have a specific requirement for an unsubstituted galactose in the nonreducing terminus and an alpha linkage between N-acetylgalactosamine and the aglycone. This is the only endoenzyme known capable of cleaving the linkage between a carbohydrate and serine or threonine residues in glycoproteins. The ability of this enzyme to act on macromolecular substrates and its pH optimum makes it ideally suited to explore the distribution and function of mucin-type glycoproteins on normal and cancer cell surfaces."}
{"id": "PMID:21881", "title": "Characterization of human thyroxine-binding globulin. Evidence for a single polypeptide chain.", "content": "Thyroxine-binding globulin (TBG) was purified from fresh human plasma by affinity, anion exchange, and gel filtration chromatography. The protein gave a single band in overloaded analytical disc gel electrophoresis. The molecular weight was 54,000 and E1%/1 cm at 280 nm, corrected for thyroxine (T4) absorbance, was 6.17. Six preparations of TBG contained from 0.09 to 0.64 mol of T4/mol; the TBG used in this study contained 0.19 mol of T4 and was able to bind an additional 0.85 mol. The carbohydrate composition was determined and accounted for 23% of the molecular weight. Four lines of chemical and physical evidence failed to demonstrate subunits. These included quantitative COOH-terminal amino acid analysis, peptide mapping and amino acid composition, treatment with sodium dodecyl sulfate, and denaturation of the reduced, alkylated protein with guanidine. From these data, we conclude that TBG is a single polypeptide chain.", "contents": "Characterization of human thyroxine-binding globulin. Evidence for a single polypeptide chain. Thyroxine-binding globulin (TBG) was purified from fresh human plasma by affinity, anion exchange, and gel filtration chromatography. The protein gave a single band in overloaded analytical disc gel electrophoresis. The molecular weight was 54,000 and E1%/1 cm at 280 nm, corrected for thyroxine (T4) absorbance, was 6.17. Six preparations of TBG contained from 0.09 to 0.64 mol of T4/mol; the TBG used in this study contained 0.19 mol of T4 and was able to bind an additional 0.85 mol. The carbohydrate composition was determined and accounted for 23% of the molecular weight. Four lines of chemical and physical evidence failed to demonstrate subunits. These included quantitative COOH-terminal amino acid analysis, peptide mapping and amino acid composition, treatment with sodium dodecyl sulfate, and denaturation of the reduced, alkylated protein with guanidine. From these data, we conclude that TBG is a single polypeptide chain."}
{"id": "PMID:21882", "title": "Structure and stability of human thyroxine-binding globulin.", "content": "The secondary and tertiary structure of human plasma thyroxine-binding globulin (TBG) was investigated by circular dichroism and fluorescence properties. The relaxation time of TBG indicated that it is a compact, symmetric molecule. It was calculated from the far ultraviolet CD spectrum that about one-half of the peptide groups are equally distributed in alpha helical and beta structures. In the near ultraviolet, the CD spectrum of TBG was modified when thyroxine was bound. TBG was stable at temperatures below 50 degrees at pH 9 and below 35 degrees at pH 10.5. Below pH 5 tryptophanyl fluorescence revealed a molecular transition which followed first order kinetics. The transition resulted in an irreversible loss of binding of the hormone. Acidification to pH 3.4 produced only a minor change in the CD spectrum, in which some of the alpha helical peptides were converted to beta structure.", "contents": "Structure and stability of human thyroxine-binding globulin. The secondary and tertiary structure of human plasma thyroxine-binding globulin (TBG) was investigated by circular dichroism and fluorescence properties. The relaxation time of TBG indicated that it is a compact, symmetric molecule. It was calculated from the far ultraviolet CD spectrum that about one-half of the peptide groups are equally distributed in alpha helical and beta structures. In the near ultraviolet, the CD spectrum of TBG was modified when thyroxine was bound. TBG was stable at temperatures below 50 degrees at pH 9 and below 35 degrees at pH 10.5. Below pH 5 tryptophanyl fluorescence revealed a molecular transition which followed first order kinetics. The transition resulted in an irreversible loss of binding of the hormone. Acidification to pH 3.4 produced only a minor change in the CD spectrum, in which some of the alpha helical peptides were converted to beta structure."}
{"id": "PMID:21883", "title": "Neurospora crassa glutamine synthetase. Role of enzyme synthesis and degradation on the regulation of enzyme concentration during exponential growth.", "content": "The specific activity of Neurospora crassa glutamine synthetase varies according to the nitrogen source in which the organism is grown. In a poor nitrogen source such as glutamate, the specific activity of the enzyme is higher than that found in good nitrogen sources such as ammonium or glutamine. These differences in specific enzyme activity correspond to differences in enzyme concentration. The relative rates of glutamine synthetase synthesis and degradation were measured in exponential cultures grown in different nitrogen sources. The differences in enzyme concentration are explained by differences in the relative rate of enzyme synthesis.", "contents": "Neurospora crassa glutamine synthetase. Role of enzyme synthesis and degradation on the regulation of enzyme concentration during exponential growth. The specific activity of Neurospora crassa glutamine synthetase varies according to the nitrogen source in which the organism is grown. In a poor nitrogen source such as glutamate, the specific activity of the enzyme is higher than that found in good nitrogen sources such as ammonium or glutamine. These differences in specific enzyme activity correspond to differences in enzyme concentration. The relative rates of glutamine synthetase synthesis and degradation were measured in exponential cultures grown in different nitrogen sources. The differences in enzyme concentration are explained by differences in the relative rate of enzyme synthesis."}
{"id": "PMID:21887", "title": "Studies of the human testis. VIII. Product activation of 17beta-hydroxysteroid oxidoreductase for testosterone.", "content": "Cell-free homogenates prepared from human testis tissue were incubated with either 1.3 x 10(-5)M[4-14C]testosterone and 2 x 10(-4)M NADP or 1.3 x 10(-5) [4-14C]nadrostenedione and 2 x 10(-4)M NADPH. Addition of non-radioactive androstenedione and testosterone to the incubation medium increased the formation of [14C]androstenedione from [4-14C]testosterone and [14C]testosterone from [4-14C]androstenedione, respectively, while addition of product nucleotide NADPH or NADP, respectively, decreased the conversions. The addition of androstenedione to the incubation medium changed the apparent optimal pH of 17beta-hydroxysteroid oxidoreductase for testosterone from 8.6 to 8.0. It appears likely that in a cell-free system human testicular 17beta-hydroxysteroid oxidoreductase not solubilized and still attached to membrane is activated by the product of the reaction catalyzed by the enzyme.", "contents": "Studies of the human testis. VIII. Product activation of 17beta-hydroxysteroid oxidoreductase for testosterone. Cell-free homogenates prepared from human testis tissue were incubated with either 1.3 x 10(-5)M[4-14C]testosterone and 2 x 10(-4)M NADP or 1.3 x 10(-5) [4-14C]nadrostenedione and 2 x 10(-4)M NADPH. Addition of non-radioactive androstenedione and testosterone to the incubation medium increased the formation of [14C]androstenedione from [4-14C]testosterone and [14C]testosterone from [4-14C]androstenedione, respectively, while addition of product nucleotide NADPH or NADP, respectively, decreased the conversions. The addition of androstenedione to the incubation medium changed the apparent optimal pH of 17beta-hydroxysteroid oxidoreductase for testosterone from 8.6 to 8.0. It appears likely that in a cell-free system human testicular 17beta-hydroxysteroid oxidoreductase not solubilized and still attached to membrane is activated by the product of the reaction catalyzed by the enzyme."}
{"id": "PMID:21888", "title": "Rapid measurement of an index of testosterone binding to serum binding globulin using ion exchange columns.", "content": "DEAE cellulose \"mini\" columns at pH 7.4 retain testosterone (T) bound to testosterone binding globulin (TeBG), which can be eluted at pH 2. Small 1:2 diluted serum or plasma samples are incubated with a tracer dose of tritiated T in pH 7.4 Tris buffer at 37 C then chilled and placed on columns at 4 C. Free and albumin bound T are washed off columns with pH 7.4 Tris buffer and columns are eluted with pH 2 Tris into vials for scintillation counting. After a simple mathematical correction for the small residual fraction of albumin bound T eluted at pH 2, we obtain a measure of TeBG binding of T which is highly correlated (r = .945) with that determined by dialysis. The method is quick, reproducible and applicable to serum or plasma volumes of 50 to 200 microliter. A single operator can process 100 samples in approximately 4 h.", "contents": "Rapid measurement of an index of testosterone binding to serum binding globulin using ion exchange columns. DEAE cellulose \"mini\" columns at pH 7.4 retain testosterone (T) bound to testosterone binding globulin (TeBG), which can be eluted at pH 2. Small 1:2 diluted serum or plasma samples are incubated with a tracer dose of tritiated T in pH 7.4 Tris buffer at 37 C then chilled and placed on columns at 4 C. Free and albumin bound T are washed off columns with pH 7.4 Tris buffer and columns are eluted with pH 2 Tris into vials for scintillation counting. After a simple mathematical correction for the small residual fraction of albumin bound T eluted at pH 2, we obtain a measure of TeBG binding of T which is highly correlated (r = .945) with that determined by dialysis. The method is quick, reproducible and applicable to serum or plasma volumes of 50 to 200 microliter. A single operator can process 100 samples in approximately 4 h."}
{"id": "PMID:21889", "title": "Identification of Neisseria by electron capture gas-liquid chromatography of metabolites in a chemically defined growth medium.", "content": "A dual-purpose study was carried out in an attempt to develop a rapid, sensitive method to identify Neisseria species by gas chromatography and to learn more about the metabolism of these organisms. Sixty-nine isolates of Neisseria were grown in a chemically defined fluid medium; the spent medium was extracted sequentially at pH 2 with diethyl ether and at pH 10 with chloroform. The pH 10 extracts were derivatized with heptafluorobutyric anhydride and analyzed by electron capture gas-liquid chromatography. The resulting spent culture medium electron capture gas-liquid chromatography profiles showed several qualitative and significant quantitative differences among the Neisseria species potentially useful in separating and identifying these organisms. Putrescine and cadaverine which were present in the spent culture medium of some Neisseria, including N. gonorrhoeae, were tentatively identified. Substituting carbohydrates for the chemically defined medium containing glucose in the base medium produced altered profiles with increased quantitative and qualitative differences.", "contents": "Identification of Neisseria by electron capture gas-liquid chromatography of metabolites in a chemically defined growth medium. A dual-purpose study was carried out in an attempt to develop a rapid, sensitive method to identify Neisseria species by gas chromatography and to learn more about the metabolism of these organisms. Sixty-nine isolates of Neisseria were grown in a chemically defined fluid medium; the spent medium was extracted sequentially at pH 2 with diethyl ether and at pH 10 with chloroform. The pH 10 extracts were derivatized with heptafluorobutyric anhydride and analyzed by electron capture gas-liquid chromatography. The resulting spent culture medium electron capture gas-liquid chromatography profiles showed several qualitative and significant quantitative differences among the Neisseria species potentially useful in separating and identifying these organisms. Putrescine and cadaverine which were present in the spent culture medium of some Neisseria, including N. gonorrhoeae, were tentatively identified. Substituting carbohydrates for the chemically defined medium containing glucose in the base medium produced altered profiles with increased quantitative and qualitative differences."}
{"id": "PMID:21890", "title": "Auditory word discrimination in male children diagnosed as having minimal brain dysfunction.", "content": "Investigated auditory word discrimination skill in children diagnosed as having minimal brain dysfunction (MBD), a heretofore unexplored topic in the study of MBD. A lack of auditory discrimination skill seems relevant to learning deficiency in language acquisition, a typical sign of MBD. The present study tested the hypothesis that phonemic aural discriminations would be difficult to make for boys diagnosed as having MBD. Errors and nonresponses made while Ss performed an extended auditory word discrimination task were compared between a group of 26 boys diagnosed as having MBD and a matched normal group. As expected, the MBD group had a significantly higher error rate than the normal group even when Ss were discriminating easy word pairs composed of dissimilar items (e.g., reading, math). These and other results suggested that the MBD group was very susceptible to fatigue even while motivated to perform well and while able to improve with practice. The relatively inferior performance of the MBD group was interpreted as resulting directly from a lack of auditory discrimination skill and indirectly from fatigue and its accompanying attention loss.", "contents": "Auditory word discrimination in male children diagnosed as having minimal brain dysfunction. Investigated auditory word discrimination skill in children diagnosed as having minimal brain dysfunction (MBD), a heretofore unexplored topic in the study of MBD. A lack of auditory discrimination skill seems relevant to learning deficiency in language acquisition, a typical sign of MBD. The present study tested the hypothesis that phonemic aural discriminations would be difficult to make for boys diagnosed as having MBD. Errors and nonresponses made while Ss performed an extended auditory word discrimination task were compared between a group of 26 boys diagnosed as having MBD and a matched normal group. As expected, the MBD group had a significantly higher error rate than the normal group even when Ss were discriminating easy word pairs composed of dissimilar items (e.g., reading, math). These and other results suggested that the MBD group was very susceptible to fatigue even while motivated to perform well and while able to improve with practice. The relatively inferior performance of the MBD group was interpreted as resulting directly from a lack of auditory discrimination skill and indirectly from fatigue and its accompanying attention loss."}
{"id": "PMID:21891", "title": "Patient characteristics and expectancy measures as factors that influence the expectancy-improvement relationship.", "content": "A recent study found factored measures of patient's expectancies for therapeutic gain significantly correlated with 1 of 15 objective measures of treatment outcome for the hospitalized patients. A subsequent study of the same relationship that used unfactored expectancy measured with a diagnostically homogenous sample of patients found the patients' expectancies significantly correlated with 10 of the same 15 measures of improvement. This study reexamined the initial expectancy-improvement data using unfactored measures of expectancy. The overall results showed that characteristics of samples of Ss and the adequacy of expectancy measures both significantly influence the results of tests of the expectancy-improvement relationship.", "contents": "Patient characteristics and expectancy measures as factors that influence the expectancy-improvement relationship. A recent study found factored measures of patient's expectancies for therapeutic gain significantly correlated with 1 of 15 objective measures of treatment outcome for the hospitalized patients. A subsequent study of the same relationship that used unfactored expectancy measured with a diagnostically homogenous sample of patients found the patients' expectancies significantly correlated with 10 of the same 15 measures of improvement. This study reexamined the initial expectancy-improvement data using unfactored measures of expectancy. The overall results showed that characteristics of samples of Ss and the adequacy of expectancy measures both significantly influence the results of tests of the expectancy-improvement relationship."}
{"id": "PMID:21892", "title": "An application of actuarial methods in psychiatric diagnosis.", "content": "An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills.", "contents": "An application of actuarial methods in psychiatric diagnosis. An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills."}
{"id": "PMID:21893", "title": "Pretty patient - healthy patient? A study of physical attractiveness and psychopathology.", "content": "Recent research has shown that physically attractive persons are viewed by others, and by themselves, as \"better\" in many ways than less attractive persons. The trend in research findings is pervasive, and a stereotype has been proposed: \"what is beautiful is good.\" This study explored the relationship between physical attractiveness and emotional adjustment of hospitalized schizophrenic patients. It was hypothesized (1) that judges would consider attractive patients better adjusted than unattractive patients; and (2) that attractive patients would appear healthier or better adjusted than unattractive patients on standard diagnostic measures. The results of multivariate analyses supported the first hypothesis, but consistently failed to support the second. Limitations of the present findings and of the \"beautiful is good\" stereotype are discussed.", "contents": "Pretty patient - healthy patient? A study of physical attractiveness and psychopathology. Recent research has shown that physically attractive persons are viewed by others, and by themselves, as \"better\" in many ways than less attractive persons. The trend in research findings is pervasive, and a stereotype has been proposed: \"what is beautiful is good.\" This study explored the relationship between physical attractiveness and emotional adjustment of hospitalized schizophrenic patients. It was hypothesized (1) that judges would consider attractive patients better adjusted than unattractive patients; and (2) that attractive patients would appear healthier or better adjusted than unattractive patients on standard diagnostic measures. The results of multivariate analyses supported the first hypothesis, but consistently failed to support the second. Limitations of the present findings and of the \"beautiful is good\" stereotype are discussed."}
{"id": "PMID:21898", "title": "Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma. Report of a case.", "content": "The syndrome of pulmonary infiltrates with eosinophilia (PIE) occurs rarely in the asthmatic patient. An unusual case is presented in which progressive bronchoconstriction and exaggerated blood eosinophilia preceded the recognition of two seemingly unrelated diseases, each of which can independently result in hypereosinophilia and the PIE syndrome. In the male patient studied, the first illness, biopsy-proved chronic eosinophilic pneumonia, was responsive to corticosteroid therapy. Four uneventful years later, polyarteritis nodosa with eventual pulmonary involvement developed. A careful search for specific underlying pulmonary and systemic disease is in order when hypereosinophilia occurs in the clinically unstable asthmatic patient.", "contents": "Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma. Report of a case. The syndrome of pulmonary infiltrates with eosinophilia (PIE) occurs rarely in the asthmatic patient. An unusual case is presented in which progressive bronchoconstriction and exaggerated blood eosinophilia preceded the recognition of two seemingly unrelated diseases, each of which can independently result in hypereosinophilia and the PIE syndrome. In the male patient studied, the first illness, biopsy-proved chronic eosinophilic pneumonia, was responsive to corticosteroid therapy. Four uneventful years later, polyarteritis nodosa with eventual pulmonary involvement developed. A careful search for specific underlying pulmonary and systemic disease is in order when hypereosinophilia occurs in the clinically unstable asthmatic patient."}
{"id": "PMID:21899", "title": "Tardive dyskinesia in psychogeriatric patients: a five-year follow-up.", "content": "The neurologic side effects of antipsychotic drugs in the treatment of major psychiatric disorders are causing great concern. The status of tardive dyskinesia in 13 elderly psychiatric patients at the 5-year follow-up point, is reported. In 11 of the 13, tardive dyskinesia persisted. tamong these 11 patients, the severity was reduced in 2, increased in 2, and unchanged in 7. Only in 2 of the total 13 subjects had the tardive dyskinesia disappeared. However, both of these patients were receiving neuroleptic drugs and had parkinsonism, a syndrome that might have masked the dyskinesia. Recommendations are made for prophylaxis and for good clinical judgment in the use of antipsychotic drugs.", "contents": "Tardive dyskinesia in psychogeriatric patients: a five-year follow-up. The neurologic side effects of antipsychotic drugs in the treatment of major psychiatric disorders are causing great concern. The status of tardive dyskinesia in 13 elderly psychiatric patients at the 5-year follow-up point, is reported. In 11 of the 13, tardive dyskinesia persisted. tamong these 11 patients, the severity was reduced in 2, increased in 2, and unchanged in 7. Only in 2 of the total 13 subjects had the tardive dyskinesia disappeared. However, both of these patients were receiving neuroleptic drugs and had parkinsonism, a syndrome that might have masked the dyskinesia. Recommendations are made for prophylaxis and for good clinical judgment in the use of antipsychotic drugs."}
{"id": "PMID:21931", "title": "A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts.", "content": "A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.", "contents": "A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts. A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant."}
{"id": "PMID:21932", "title": "pH as an indicator of free fatty acid release from adipocytes.", "content": "A convenient method of measuring initial rates of free fatty acid efflux from isolated adipocytes during triglyceride breakdown by hormone-sensitive lipase is described. The procedure is based on the dissociation of protons from carboxyl groups of free fatty acids. A recording pH meter is used to monitor H+ concentration in the medium continuously as an index of free fatty acid release. A stoichiometric relationship was demonstrated between proton release and extracellular free fatty acid concentration as determined by the 63Ni radioassay method of Ho (1970. Anal. Biochem. 36: 105-113). An acid pH (6.8) caused a reduction in proton release, which was immediately and completely reversed by raising the pH to 7.4.", "contents": "pH as an indicator of free fatty acid release from adipocytes. A convenient method of measuring initial rates of free fatty acid efflux from isolated adipocytes during triglyceride breakdown by hormone-sensitive lipase is described. The procedure is based on the dissociation of protons from carboxyl groups of free fatty acids. A recording pH meter is used to monitor H+ concentration in the medium continuously as an index of free fatty acid release. A stoichiometric relationship was demonstrated between proton release and extracellular free fatty acid concentration as determined by the 63Ni radioassay method of Ho (1970. Anal. Biochem. 36: 105-113). An acid pH (6.8) caused a reduction in proton release, which was immediately and completely reversed by raising the pH to 7.4."}
{"id": "PMID:21933", "title": "Type I Escherichia coli pili: characterization of binding to monkey kidney cells.", "content": "We have demonstrated binding of purified pili from a strain of Escherichia coli to Vero cell monolayers as a model of prokaryotic-eukaryotic cell adherence. Pili bound to the tissue culture in a rapid reaction that did not require enzymatic activation. Attachment occurred optimally at pH 4-5 and could be inhibited by analogues of D-mannose, anti-pili antibodies, or by preincubation of tissue cells with mannose-specific plant lectins. Binding remained after treatment of the monolayer with glycosidases, trypsin, or a protease mixture but was enhanced after neuraminidase treatment. These results indicate that bacterial binding can occur via pili which act like lectins and presumably bind to mannose-containing glycoproteins on mammalian cell surfaces.", "contents": "Type I Escherichia coli pili: characterization of binding to monkey kidney cells. We have demonstrated binding of purified pili from a strain of Escherichia coli to Vero cell monolayers as a model of prokaryotic-eukaryotic cell adherence. Pili bound to the tissue culture in a rapid reaction that did not require enzymatic activation. Attachment occurred optimally at pH 4-5 and could be inhibited by analogues of D-mannose, anti-pili antibodies, or by preincubation of tissue cells with mannose-specific plant lectins. Binding remained after treatment of the monolayer with glycosidases, trypsin, or a protease mixture but was enhanced after neuraminidase treatment. These results indicate that bacterial binding can occur via pili which act like lectins and presumably bind to mannose-containing glycoproteins on mammalian cell surfaces."}
{"id": "PMID:21934", "title": "Isolation of pH-optima and apparent Michaelis constants of highly purified enzymes from human and animal sources. Comparison of enzymes of human and animal origin, I.", "content": "Enzymes from animal sources are frequently used for quality control of enzyme activity determination in clinical chemistry. For this purpose they should be very similar to human enzymes. It is shown that preparations of enzymes of diagnostic interest from human and porcine organs, purified in exactly the same way, have very similar pH-optima and apparent Michaelis constants for their substrates.", "contents": "Isolation of pH-optima and apparent Michaelis constants of highly purified enzymes from human and animal sources. Comparison of enzymes of human and animal origin, I. Enzymes from animal sources are frequently used for quality control of enzyme activity determination in clinical chemistry. For this purpose they should be very similar to human enzymes. It is shown that preparations of enzymes of diagnostic interest from human and porcine organs, purified in exactly the same way, have very similar pH-optima and apparent Michaelis constants for their substrates."}
{"id": "PMID:21935", "title": "A nurse practitioner in a family practice residency: role description and impact on continuity of the practitioner-patient relationship.", "content": "The nurse practitioner and physician's assistant are new health practitioners providing primary health care. When teamed with family physicians, these new health practitioners can extend patient services. Family physicians should be trained to work with new health practitioners effectively. Presented is a model where a nurse practitioner and family practice residents work as co-practitioners in a family practice unit. A nurse practitioner in this role can improve the continuity of the relationship between patient and provider in a family practice residency.", "contents": "A nurse practitioner in a family practice residency: role description and impact on continuity of the practitioner-patient relationship. The nurse practitioner and physician's assistant are new health practitioners providing primary health care. When teamed with family physicians, these new health practitioners can extend patient services. Family physicians should be trained to work with new health practitioners effectively. Presented is a model where a nurse practitioner and family practice residents work as co-practitioners in a family practice unit. A nurse practitioner in this role can improve the continuity of the relationship between patient and provider in a family practice residency."}
{"id": "PMID:21936", "title": "Regulation of the bacterial microflora of the vagina in cyclic female rats.", "content": "The bacterial microflora was examined in the vagina of cyclic female rats kept under normal laboratory conditions. Large variations occurred during the cycle with high numbers of bacteria (10(5)-10(8) per vagina) during proestrus and estrus and low numbers (10(1)-10(4) per vagina) during the diestrus period. Histological analysis of in situ vaginal tissue and transplanted vaginal tissue revealed an association of high bacterial numbers with the presence of large amounts of cellular debris in the vaginal lumen during the period of epithelial keratinization. Absence of phagocytosis in leucocytes at mestestrus suggested that leucocytes did not play an active role in reduction of bacterial numbers between estrus and metestrus. Accurate measurement of the pH in the vaginal lumen failed to reveal differences which could explain the reduction in bacterial numbers between estrus and metestrus. The cyclic changes in the bacterial population-consisting of species which are normally present in the intestinal flora-- seem to be controlled by cyclic changes in the amounts of cellular debris in the vaginal lumen.", "contents": "Regulation of the bacterial microflora of the vagina in cyclic female rats. The bacterial microflora was examined in the vagina of cyclic female rats kept under normal laboratory conditions. Large variations occurred during the cycle with high numbers of bacteria (10(5)-10(8) per vagina) during proestrus and estrus and low numbers (10(1)-10(4) per vagina) during the diestrus period. Histological analysis of in situ vaginal tissue and transplanted vaginal tissue revealed an association of high bacterial numbers with the presence of large amounts of cellular debris in the vaginal lumen during the period of epithelial keratinization. Absence of phagocytosis in leucocytes at mestestrus suggested that leucocytes did not play an active role in reduction of bacterial numbers between estrus and metestrus. Accurate measurement of the pH in the vaginal lumen failed to reveal differences which could explain the reduction in bacterial numbers between estrus and metestrus. The cyclic changes in the bacterial population-consisting of species which are normally present in the intestinal flora-- seem to be controlled by cyclic changes in the amounts of cellular debris in the vaginal lumen."}
{"id": "PMID:21937", "title": "Effects of neurotransmitters upon the discharge of secretory product from the cutaneous glands of the red-spotted newt.", "content": "The effects of sympathetic and parasympathetic agonists and antagonists on discharge of secretory product by the granular and mucous glands were examined in the red-spotted newt, Notopthalmus viridescens viridescens. Observations were made also on the South African clawed toad. Xenopus laevis, the grass frog, Rana pipiens, and the crested newt, Triturus cristatus. In contrast to the granular glands of the South African clawed toad and the grass frog, which were stimulated by alpha-adrenergic agents, those of the red-spotted newt discharge in response to acetylcholine, either in vitro when added to the Holtfreter's solution in which explants were incubated, or in vivo when injected subcutaneously. Granular glands of the crested newt were also dischared in response to subcutaneous injection of acetylcholine. Stimulation of the granular glands by acetylcholine was blocked by atopine but not by tubocurarie, indicating that the cholinergic receptors are muscarinic rather than nicotinic. The mucous glands of the red-spotted newt, on the other hand, did not discharge in response to either acetylcholine or to adrenergic agents.", "contents": "Effects of neurotransmitters upon the discharge of secretory product from the cutaneous glands of the red-spotted newt. The effects of sympathetic and parasympathetic agonists and antagonists on discharge of secretory product by the granular and mucous glands were examined in the red-spotted newt, Notopthalmus viridescens viridescens. Observations were made also on the South African clawed toad. Xenopus laevis, the grass frog, Rana pipiens, and the crested newt, Triturus cristatus. In contrast to the granular glands of the South African clawed toad and the grass frog, which were stimulated by alpha-adrenergic agents, those of the red-spotted newt discharge in response to acetylcholine, either in vitro when added to the Holtfreter's solution in which explants were incubated, or in vivo when injected subcutaneously. Granular glands of the crested newt were also dischared in response to subcutaneous injection of acetylcholine. Stimulation of the granular glands by acetylcholine was blocked by atopine but not by tubocurarie, indicating that the cholinergic receptors are muscarinic rather than nicotinic. The mucous glands of the red-spotted newt, on the other hand, did not discharge in response to either acetylcholine or to adrenergic agents."}
{"id": "PMID:21938", "title": "Glutamate dehydrogenases from tissues of the ribbed mussel Modiolus demissus: ADP activation and possible physiological significance.", "content": "Glutamate dehydrogenase (E.C. 14.1.3) was localized in the mitochondria from heart, gill, mantle and hepatopancreas of this euryhaline bivalve mollusc. Activity levels were low (0.1-0.4 mumoles/min/g wet weight) in all tissues when assayed in the glutamate forming direction. Partially purified gill mitochondrial GDH was most active at pH 8.5. The rate in the glutamate deaminating direction was 10-20% of the rate in the glutamate forming direction. ADP at apparent Ka concentrations of micrometer (glutamate formation) and 170 micrometer (glutamate deamination) enhanced GDH activity, 8- and 4-fold respectively. GDH, in vivo, is probably in the activated form and appears to function in glutamate synthesis rather than ammonia formation. However, based on the low activities obtained, the role of GDH in salinity induced amino acid synthesis seems minimal.", "contents": "Glutamate dehydrogenases from tissues of the ribbed mussel Modiolus demissus: ADP activation and possible physiological significance. Glutamate dehydrogenase (E.C. 14.1.3) was localized in the mitochondria from heart, gill, mantle and hepatopancreas of this euryhaline bivalve mollusc. Activity levels were low (0.1-0.4 mumoles/min/g wet weight) in all tissues when assayed in the glutamate forming direction. Partially purified gill mitochondrial GDH was most active at pH 8.5. The rate in the glutamate deaminating direction was 10-20% of the rate in the glutamate forming direction. ADP at apparent Ka concentrations of micrometer (glutamate formation) and 170 micrometer (glutamate deamination) enhanced GDH activity, 8- and 4-fold respectively. GDH, in vivo, is probably in the activated form and appears to function in glutamate synthesis rather than ammonia formation. However, based on the low activities obtained, the role of GDH in salinity induced amino acid synthesis seems minimal."}
{"id": "PMID:21939", "title": "On the induction of zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Piromonas communis and Sphaeromonas communis.", "content": "The plant components inducing zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Sphaeromonas communis and Piromonas communis were widely distributed in the plant kingdom with no apparent taxonomic relationship. In Lolium perenne L. (perennial rye-grass) and Hordeum distichon (barley), the components were principally present in the leaves and aerial tissues. Sufficient inducer was present in the normal diet of the host animal to trigger the differentiation and release of the zoospores from all the sporangia of each phycomycete species present in the rumen fluid tested. The inducers were unstable to oxygen, especially at elevated temperatures, and were destroyed by rumen micro-organisms. They may be similar compounds for each species.", "contents": "On the induction of zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Piromonas communis and Sphaeromonas communis. The plant components inducing zoosporogenesis in the rumen phycomycetes Neocallimastix frontalis, Sphaeromonas communis and Piromonas communis were widely distributed in the plant kingdom with no apparent taxonomic relationship. In Lolium perenne L. (perennial rye-grass) and Hordeum distichon (barley), the components were principally present in the leaves and aerial tissues. Sufficient inducer was present in the normal diet of the host animal to trigger the differentiation and release of the zoospores from all the sporangia of each phycomycete species present in the rumen fluid tested. The inducers were unstable to oxygen, especially at elevated temperatures, and were destroyed by rumen micro-organisms. They may be similar compounds for each species."}
{"id": "PMID:21940", "title": "Studies on the mechanism of action of oxygen-labile haemolysins.", "content": "The sensitivities of the binding step and the lytic step of haemolysis by pneumolysin to the action of various inhibitors and to variations in the assay conditions were studied. Binding was inhibited by HgCl2 and N-ethylmaleimide. Lysis by previously fixed lysin was insensitive to HgCl2 and only slightly sensitive to N-ethylmaleimide. Binding of pneumolysin was independent of ionic strength. Binding of pneumolysin and streptolysin O decreased above pH 8-0 and 8-4 respectively. These results suggest that binding requires a non-ionized unsubstituted sulphydryl group. Incubation of erythrocytes with NaF caused inhibition of pneumolysin, indicating that some metabolic function of the cell may be involved in lysis. The action of streptolysin O was not affected by NaF.", "contents": "Studies on the mechanism of action of oxygen-labile haemolysins. The sensitivities of the binding step and the lytic step of haemolysis by pneumolysin to the action of various inhibitors and to variations in the assay conditions were studied. Binding was inhibited by HgCl2 and N-ethylmaleimide. Lysis by previously fixed lysin was insensitive to HgCl2 and only slightly sensitive to N-ethylmaleimide. Binding of pneumolysin was independent of ionic strength. Binding of pneumolysin and streptolysin O decreased above pH 8-0 and 8-4 respectively. These results suggest that binding requires a non-ionized unsubstituted sulphydryl group. Incubation of erythrocytes with NaF caused inhibition of pneumolysin, indicating that some metabolic function of the cell may be involved in lysis. The action of streptolysin O was not affected by NaF."}
{"id": "PMID:21941", "title": "The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli.", "content": "Mutants of Escherichia coli K12 have been isolated that grow on media containing pyruvate of proline as sole carbon sources despite the presence of 10 or 50 mM-sodium fluoroacetate. Such mutants lack either acetate kinase [ATP: acetate phosphotransferase; EC 2.7.2.1] or phosphotransacetylase [acetyl-CoA: orthophosphate acetyltransferase; EC 2.3.1.8] activity. Unlike wild-type E. coli, phosphotransacetylase mutants do not excrete acetate when growing aerobically or anaerobically on glucose; their anaerobic growth on this sugar is slow. The genes that specify acetate kinase (ack) and phosphotransacetylase (pta) activities are cotransducible with each other and with purF and are thus located at about min 50 on the E. coli linkage map. Although Pta- and Ack- mutants are greatly impaired in their growth on acetate, they incorporate [2-14C]acetate added to cultures growing on glycerol, but not on glucose. An inducible acetyl-CoA synthetase [acetate: CoA ligase (AMP-forming); EC 6.2.1.1] effects this uptake of acetate.", "contents": "The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli. Mutants of Escherichia coli K12 have been isolated that grow on media containing pyruvate of proline as sole carbon sources despite the presence of 10 or 50 mM-sodium fluoroacetate. Such mutants lack either acetate kinase [ATP: acetate phosphotransferase; EC 2.7.2.1] or phosphotransacetylase [acetyl-CoA: orthophosphate acetyltransferase; EC 2.3.1.8] activity. Unlike wild-type E. coli, phosphotransacetylase mutants do not excrete acetate when growing aerobically or anaerobically on glucose; their anaerobic growth on this sugar is slow. The genes that specify acetate kinase (ack) and phosphotransacetylase (pta) activities are cotransducible with each other and with purF and are thus located at about min 50 on the E. coli linkage map. Although Pta- and Ack- mutants are greatly impaired in their growth on acetate, they incorporate [2-14C]acetate added to cultures growing on glycerol, but not on glucose. An inducible acetyl-CoA synthetase [acetate: CoA ligase (AMP-forming); EC 6.2.1.1] effects this uptake of acetate."}
{"id": "PMID:21942", "title": "Adsorption of a phage tail-like bacteriocin to isolated lipopolysaccharide of Rhizobium.", "content": "Purified lipopolysaccharide (LPS) from the bacteriocin sensitive strain Rhizobium lupini i6-2 was shown to neutralize the killing activity of the bacteriocin. In the electron microscopical preparation the phage tail-like bacteriocin appears to be adsorbed to the LPS; the tail sheath is contracted and the fibres are oriented towards the LPS ribbon. In contrast, no interaction was observed between the bacteriocin and the LPS of two resistant strains of Rhizobium (16-2/Ii and 16-3). The inactivation of the bacteriocin by LPS depends on salt concentration, pH, and temperature. The receptor activity of LPS was destroyed by mild acid hydrolysis and by treatment with deoxycholate, which indicates that the micellar structure of the LPS is necessary for bacteriocin adsorption. The chemical composition of the 16-2 LPS was compared to that of the LPS of two resistant strains. In the case of 16-2/ii LPS minor modifications suffice to confer resistance against the bacteriocin.", "contents": "Adsorption of a phage tail-like bacteriocin to isolated lipopolysaccharide of Rhizobium. Purified lipopolysaccharide (LPS) from the bacteriocin sensitive strain Rhizobium lupini i6-2 was shown to neutralize the killing activity of the bacteriocin. In the electron microscopical preparation the phage tail-like bacteriocin appears to be adsorbed to the LPS; the tail sheath is contracted and the fibres are oriented towards the LPS ribbon. In contrast, no interaction was observed between the bacteriocin and the LPS of two resistant strains of Rhizobium (16-2/Ii and 16-3). The inactivation of the bacteriocin by LPS depends on salt concentration, pH, and temperature. The receptor activity of LPS was destroyed by mild acid hydrolysis and by treatment with deoxycholate, which indicates that the micellar structure of the LPS is necessary for bacteriocin adsorption. The chemical composition of the 16-2 LPS was compared to that of the LPS of two resistant strains. In the case of 16-2/ii LPS minor modifications suffice to confer resistance against the bacteriocin."}
{"id": "PMID:21943", "title": "Alertness and clear thinking as characteristics of high naturally occurring autonomic nervous system arousal.", "content": "Studies of the effect of induced mood on the autonomic nervous system (ANS) suggested that naturally occurring mood might also covary with the ANS. Ss were 13 men and women aged 20 to 70. Fatigue, confusion, and depression were measured on the Profile of Mood States, while barometric pressure and the ANS indices of heart rate and body temperature were also recorded. Fatigue and confusion each showed negative relationships to both heart rate and body temperature. Barometric pressure showed a suggestively positive relationship to the mood of depression. Hypothalamic serotonin concentration was suggested as a central factor producing the covariations between the mood indices (alertness and clear thinking) and the ANS measures.", "contents": "Alertness and clear thinking as characteristics of high naturally occurring autonomic nervous system arousal. Studies of the effect of induced mood on the autonomic nervous system (ANS) suggested that naturally occurring mood might also covary with the ANS. Ss were 13 men and women aged 20 to 70. Fatigue, confusion, and depression were measured on the Profile of Mood States, while barometric pressure and the ANS indices of heart rate and body temperature were also recorded. Fatigue and confusion each showed negative relationships to both heart rate and body temperature. Barometric pressure showed a suggestively positive relationship to the mood of depression. Hypothalamic serotonin concentration was suggested as a central factor producing the covariations between the mood indices (alertness and clear thinking) and the ANS measures."}
{"id": "PMID:21944", "title": "Effects of denervation on the neuraminidase activity of slow and fast muscles of rabbits.", "content": "The presence in skeletal muscles of rabbits of neuraminidase activity on sialyl lactose was demonstrated. By comparing the specific activity of this enzyme in different control muscles, it was shown that it was 2.3 times higher in the slow than in the fast muscles. Seven days after denervation, we observed a significant increase of activity in fast muscle and a significant decrease of activity in slow muscle. These results, together with previous data, are in favour of the hypothesis that turnover of muscle glycoconjugates is under a type-specific neural control.", "contents": "Effects of denervation on the neuraminidase activity of slow and fast muscles of rabbits. The presence in skeletal muscles of rabbits of neuraminidase activity on sialyl lactose was demonstrated. By comparing the specific activity of this enzyme in different control muscles, it was shown that it was 2.3 times higher in the slow than in the fast muscles. Seven days after denervation, we observed a significant increase of activity in fast muscle and a significant decrease of activity in slow muscle. These results, together with previous data, are in favour of the hypothesis that turnover of muscle glycoconjugates is under a type-specific neural control."}
{"id": "PMID:21945", "title": "Influence of zinc deficiency on retinal reductase and oxidase activities in rat liver and testes.", "content": "The influence of zinc deficiency on vitamin A metabolism in rats was investigated by assessing two specific enzymes involved in its metabolism viz retinal reductase and retinal oxidase in the liver as well as in the testes. The activity of retinal reductase in the liver was not altered in zinc deficiency. Retinal oxidase activity on the other hand, was increased approximately 1.5 fold over the pair-fed controls. In contrast, both retinal reductase and oxidase in the testes were decreased during zinc deficiency. The effects of zinic deficiency on vitamin A metabolism in the liver could be partly attributed to the secondary effect of reduced food intake and growth. However, the effects seen in the testes on the metabolic enzymes of vitamin A appear to be due to zinc deficiency per se. The liver concentration of vitamin A (microgram/g) as well as total vitamin A (microgram/liver) were higher in the zinc-deficient rats when compared to the zinc-sufficient rats although not significantly different from the pair-fed controls. In aggreement with previous reports, the plasma vitamin A in zinc-deficient rats were found to be markedly lowered compared to zinc sufficient ad libitum controls.", "contents": "Influence of zinc deficiency on retinal reductase and oxidase activities in rat liver and testes. The influence of zinc deficiency on vitamin A metabolism in rats was investigated by assessing two specific enzymes involved in its metabolism viz retinal reductase and retinal oxidase in the liver as well as in the testes. The activity of retinal reductase in the liver was not altered in zinc deficiency. Retinal oxidase activity on the other hand, was increased approximately 1.5 fold over the pair-fed controls. In contrast, both retinal reductase and oxidase in the testes were decreased during zinc deficiency. The effects of zinic deficiency on vitamin A metabolism in the liver could be partly attributed to the secondary effect of reduced food intake and growth. However, the effects seen in the testes on the metabolic enzymes of vitamin A appear to be due to zinc deficiency per se. The liver concentration of vitamin A (microgram/g) as well as total vitamin A (microgram/liver) were higher in the zinc-deficient rats when compared to the zinc-sufficient rats although not significantly different from the pair-fed controls. In aggreement with previous reports, the plasma vitamin A in zinc-deficient rats were found to be markedly lowered compared to zinc sufficient ad libitum controls."}
{"id": "PMID:21948", "title": "Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium.", "content": "The rate of phenothiazine degradation in an acidic oxygen-saturated medium was studied. 3H-Phenothiazine-3-one and phenothiazine 5-oxide are produced by parallel reactions, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one is produced in a more complex manner. The overall phenothiazine degradation rate appears to be pH independent up to pH 7.0. The degradation kinetics of 10-methylphenothiazine were studied after isolation and identification of its degradation products, 10-methylphenothiazine 5-oxide and 3H-phenothiazine-3-one. The main degradation product is 10-methylphenothiazine 5-oxide; but at low pH values and high temperatures, more 3H-phenothiazine-3-one is formed. The degradation rate of 10-methylphenothiazine is pH independent up to pH 7.", "contents": "Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium. The rate of phenothiazine degradation in an acidic oxygen-saturated medium was studied. 3H-Phenothiazine-3-one and phenothiazine 5-oxide are produced by parallel reactions, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one is produced in a more complex manner. The overall phenothiazine degradation rate appears to be pH independent up to pH 7.0. The degradation kinetics of 10-methylphenothiazine were studied after isolation and identification of its degradation products, 10-methylphenothiazine 5-oxide and 3H-phenothiazine-3-one. The main degradation product is 10-methylphenothiazine 5-oxide; but at low pH values and high temperatures, more 3H-phenothiazine-3-one is formed. The degradation rate of 10-methylphenothiazine is pH independent up to pH 7."}
{"id": "PMID:21949", "title": "Mechanism for phenothiazine oxidation.", "content": "The mechanism of phenothiazine degradation was studied by following the degradation of 3,10'-diphenothiazine in ethanol-water mixtures as well as the electrochemical oxidation of phenothiazine. A mechanism, including the formation of an oxidized dimer and some polymers, is suggested.", "contents": "Mechanism for phenothiazine oxidation. The mechanism of phenothiazine degradation was studied by following the degradation of 3,10'-diphenothiazine in ethanol-water mixtures as well as the electrochemical oxidation of phenothiazine. A mechanism, including the formation of an oxidized dimer and some polymers, is suggested."}
{"id": "PMID:21950", "title": "Synthesis, physicochemical properties, and antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes.", "content": "To study the effect of substituents on the antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes, a series of compounds was designed and synthesized in which the substituent on the 1-phenyl was an electron-withdrawing group and the substituent on the 3-benzyl had a broad range of physicochemical properties. Of the 13 analogs prepared and tested against Sarcoma-180 in the mouse, five showed significant activity. The results were submitted to discriminant analysis to determine structure-activity relationships.", "contents": "Synthesis, physicochemical properties, and antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes. To study the effect of substituents on the antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes, a series of compounds was designed and synthesized in which the substituent on the 1-phenyl was an electron-withdrawing group and the substituent on the 3-benzyl had a broad range of physicochemical properties. Of the 13 analogs prepared and tested against Sarcoma-180 in the mouse, five showed significant activity. The results were submitted to discriminant analysis to determine structure-activity relationships."}
{"id": "PMID:21951", "title": "Biopharmaceutic factors that influence effects of anticholinergic drugs: comparison of propantheline, hexocyclium, and isopropamide.", "content": "The antisecretory (determined from salivary flow rates) and antimotility (determined from riboflavin absorption) effects of usually recommended doses of propantheline, hexocyclium, and isopropamide were compared in four adult volunteers. Both propantheline and hexocyclium significantly decreased salivary flow and increased riboflavin absorption. Although the usual dose of propantheline was about twice as effective as the usual dose of hexocyclium in suppressing salivary flow, these doses produced comparable effects on riboflavin absorption. Isopropamide had little or no effect on either the salivary flow rate or riboflavin absorption. Propantheline and hexocyclium elicited little effect on salivary flow when administered after a meal. Prolonged-release dosage forms of these drugs produced effects comparable to those produced by much smaller doses in conventional tablets and gave no indication of providing prolonged anticholinergic effects.", "contents": "Biopharmaceutic factors that influence effects of anticholinergic drugs: comparison of propantheline, hexocyclium, and isopropamide. The antisecretory (determined from salivary flow rates) and antimotility (determined from riboflavin absorption) effects of usually recommended doses of propantheline, hexocyclium, and isopropamide were compared in four adult volunteers. Both propantheline and hexocyclium significantly decreased salivary flow and increased riboflavin absorption. Although the usual dose of propantheline was about twice as effective as the usual dose of hexocyclium in suppressing salivary flow, these doses produced comparable effects on riboflavin absorption. Isopropamide had little or no effect on either the salivary flow rate or riboflavin absorption. Propantheline and hexocyclium elicited little effect on salivary flow when administered after a meal. Prolonged-release dosage forms of these drugs produced effects comparable to those produced by much smaller doses in conventional tablets and gave no indication of providing prolonged anticholinergic effects."}
{"id": "PMID:21952", "title": "Nature of acid-induced fluorescence of 17alpha-methyltestosterone.", "content": "The fluorescence of the 17alpha-methyltestosterone-trichloroacetic acid reaction product, 1,2,10,15,16,17-hexahydro-10,17,17-trimethylcyclopenta[alpha]phenanthren-3-one, in strong acid was investigated. Structural requirements for fluorescence were derived from absorption and fluorescence studies of related phenanthrenones and cinnamylidene compounds possessing a similar chromophore. All compounds showed fluorescence intensity that was structure and pH dependent. Fluorescence is attributed to both enol and protonated species.", "contents": "Nature of acid-induced fluorescence of 17alpha-methyltestosterone. The fluorescence of the 17alpha-methyltestosterone-trichloroacetic acid reaction product, 1,2,10,15,16,17-hexahydro-10,17,17-trimethylcyclopenta[alpha]phenanthren-3-one, in strong acid was investigated. Structural requirements for fluorescence were derived from absorption and fluorescence studies of related phenanthrenones and cinnamylidene compounds possessing a similar chromophore. All compounds showed fluorescence intensity that was structure and pH dependent. Fluorescence is attributed to both enol and protonated species."}
{"id": "PMID:21953", "title": "Indolizine derivativatives with biological activity III: 3-(3-Aminopropyl)-2-methylindolizine, 3-(3-Aminopropyl)-2-methyl-5,6,7,8-tetrahydroindolizine, and their N -alkyl derivatives.", "content": "The syntheses and a preliminary pharmacological evaluation of some aminopropylindolizines and aminopropyltetrahydroindolizines are reported. All compounds showed anti-5-hydroxytryptamine, anti-histamine, and antiacetylcholine activities. Some also exhibited weak CNS activity.", "contents": "Indolizine derivativatives with biological activity III: 3-(3-Aminopropyl)-2-methylindolizine, 3-(3-Aminopropyl)-2-methyl-5,6,7,8-tetrahydroindolizine, and their N -alkyl derivatives. The syntheses and a preliminary pharmacological evaluation of some aminopropylindolizines and aminopropyltetrahydroindolizines are reported. All compounds showed anti-5-hydroxytryptamine, anti-histamine, and antiacetylcholine activities. Some also exhibited weak CNS activity."}
{"id": "PMID:21954", "title": "Fluorescence properties of glafenine.", "content": "The fluorescence properties of glafenine are partly caused by the anthranilic acid nucleus of the molecule. Correlations are made between fluorescence capacities and UV absorbance. Analytical determinations can be carried out in different solvents, e.g., ether, benzene, and ethanol. Linearity of the emission intensity with the concentration, limiting detectable sample concentrations, and Stokes shifts are reported.", "contents": "Fluorescence properties of glafenine. The fluorescence properties of glafenine are partly caused by the anthranilic acid nucleus of the molecule. Correlations are made between fluorescence capacities and UV absorbance. Analytical determinations can be carried out in different solvents, e.g., ether, benzene, and ethanol. Linearity of the emission intensity with the concentration, limiting detectable sample concentrations, and Stokes shifts are reported."}
{"id": "PMID:21957", "title": "Effects of 4-aminopyridine at the frog neuromuscular junction.", "content": "Micromolar concentrations of 4-aminopyridine (4-AP) were able to increase the amplitude of the end-plate current in frog neuromuscular junction blocked either by d-tubocurarine or by low Ca++ high Mg++ medium. The end-plate potential was also increased. These effects were reversible. The changes in the end-plate current amplitude observed after 4-AP treatment had no effect on the end-plate current time course. There was no significant difference in the resting membrane potential or mean amplitude and frequency of spontaneous miniature end-plate potentials in the presence of 4-AP. The quantal content of the end-plate potential was increased in every preparation tested and the minimal synpatic delay was lengthened in a dose-related way. 4-AP did not modify the dependence of the amplitude of the end-plate current on membrane potential. In the presence of 4-AP, the time constant of the falling phase of the end-plate current remained an exponential function of the membrane potential. The end-plate current equilibrium potential was unaffected by 4-AP. The increase in the amount of acetylcholine released by nerve impulse induced by 4-AP occurs without modification in the calcium cooperativity. The authors suggest that 4-AP, by prolonging the presynaptic action potential, could increase calcium concentration in the nerve terminal and, thus, the transmitter release.", "contents": "Effects of 4-aminopyridine at the frog neuromuscular junction. Micromolar concentrations of 4-aminopyridine (4-AP) were able to increase the amplitude of the end-plate current in frog neuromuscular junction blocked either by d-tubocurarine or by low Ca++ high Mg++ medium. The end-plate potential was also increased. These effects were reversible. The changes in the end-plate current amplitude observed after 4-AP treatment had no effect on the end-plate current time course. There was no significant difference in the resting membrane potential or mean amplitude and frequency of spontaneous miniature end-plate potentials in the presence of 4-AP. The quantal content of the end-plate potential was increased in every preparation tested and the minimal synpatic delay was lengthened in a dose-related way. 4-AP did not modify the dependence of the amplitude of the end-plate current on membrane potential. In the presence of 4-AP, the time constant of the falling phase of the end-plate current remained an exponential function of the membrane potential. The end-plate current equilibrium potential was unaffected by 4-AP. The increase in the amount of acetylcholine released by nerve impulse induced by 4-AP occurs without modification in the calcium cooperativity. The authors suggest that 4-AP, by prolonging the presynaptic action potential, could increase calcium concentration in the nerve terminal and, thus, the transmitter release."}
{"id": "PMID:21958", "title": "Pharmacologic studies on W10,294A, a new bronchodilator.", "content": "W10,294A (1,2,3,4-tetrahydro-8,9-dimethoxy-3(2-piperidinoethyl)-5H-[1] benzopyrano [3,4-c] pyridin-5-one dihydrochloride) is a potent antagonist of the bronchoconstriction induced by histamine, methacholine or acetylcholine. In vitro evaluation on guinea pig trachea indicated that W10,294A had both direct smooth muscle relaxant activity and modest antihistaminic properties. Resistance and dynamic compliance measurements in anesthetized dogs indicated that W10,294A prevented or reversed bronchoconstriction due to histamine or pilocapine. Bronchodilator activity of long duration was observed in dogs after oral administration. W10,294A was compared with aminophylline in several tests. W10,294A was 6 times more potent than aminophylline in relaxing isolated guinea-pig trachea. In the anesthetized dog W10,294A was more potent and longer acting than aminophylline in reversing pilocarpine-induced bronchospasm. The bronchodilator activity of W10,294A was not blocked by the beta adrenoceptor antagonist bunolol. Comparative studies in dogs and guinea pigs, using identical doses, showed that W10,294A had considerably less effect on the cardiovascular system than did aminophylline.", "contents": "Pharmacologic studies on W10,294A, a new bronchodilator. W10,294A (1,2,3,4-tetrahydro-8,9-dimethoxy-3(2-piperidinoethyl)-5H-[1] benzopyrano [3,4-c] pyridin-5-one dihydrochloride) is a potent antagonist of the bronchoconstriction induced by histamine, methacholine or acetylcholine. In vitro evaluation on guinea pig trachea indicated that W10,294A had both direct smooth muscle relaxant activity and modest antihistaminic properties. Resistance and dynamic compliance measurements in anesthetized dogs indicated that W10,294A prevented or reversed bronchoconstriction due to histamine or pilocapine. Bronchodilator activity of long duration was observed in dogs after oral administration. W10,294A was compared with aminophylline in several tests. W10,294A was 6 times more potent than aminophylline in relaxing isolated guinea-pig trachea. In the anesthetized dog W10,294A was more potent and longer acting than aminophylline in reversing pilocarpine-induced bronchospasm. The bronchodilator activity of W10,294A was not blocked by the beta adrenoceptor antagonist bunolol. Comparative studies in dogs and guinea pigs, using identical doses, showed that W10,294A had considerably less effect on the cardiovascular system than did aminophylline."}
{"id": "PMID:21962", "title": "Combining therapeutic approaches.", "content": "It would seem on the surface that psychotherapeutic approaches as different as psychoanalysis and behavioral therapy have little in common. In fact, they seem to be similar in terms of expectation of help, nonconfirming experiences, informational learning, changes in self-concept, reinforcement/influence, paradox, and problem solving. Therapists who work with clients who present life-threatening symptoms, self-reinforcing cycles, and/or therapeutic engagement difficulties may do well to consider ways to combine therapeutic approaches in order to deal with these sticky therapeutic problems.", "contents": "Combining therapeutic approaches. It would seem on the surface that psychotherapeutic approaches as different as psychoanalysis and behavioral therapy have little in common. In fact, they seem to be similar in terms of expectation of help, nonconfirming experiences, informational learning, changes in self-concept, reinforcement/influence, paradox, and problem solving. Therapists who work with clients who present life-threatening symptoms, self-reinforcing cycles, and/or therapeutic engagement difficulties may do well to consider ways to combine therapeutic approaches in order to deal with these sticky therapeutic problems."}
{"id": "PMID:21963", "title": "Orally active esters of cephalosporin antibiotics. Synthesis and biological properties of acyloxymethyl esters of 7-(D-2-amino-2-phenylacetamido)-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid.", "content": "The synthesis of the acetoxymethyl (AOM), pivaloloxymethyl (POM), and phthalidyl (PHTH) esters of 7-[D-(-)-2-amino-2-phenylacetamido]-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid (1a), a broad-spectrum semisynthetic cephalosporin antibiotic, is described. These esters were examined as potential orally active antibiotic prodrugs. The superior oral absorption of the three esters relative to the unesterified parent, 1a, is demonstrated by differential blood levels as well as measurement of the rate at which doses of the ester leave the gastrointestinal tract and appear in the urine. A study of the decreased stability of the three esters relative to 1a at pH 4.5, 6.5, and 7.5 is also presented.", "contents": "Orally active esters of cephalosporin antibiotics. Synthesis and biological properties of acyloxymethyl esters of 7-(D-2-amino-2-phenylacetamido)-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid. The synthesis of the acetoxymethyl (AOM), pivaloloxymethyl (POM), and phthalidyl (PHTH) esters of 7-[D-(-)-2-amino-2-phenylacetamido]-3-[5-methyl-(1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylic acid (1a), a broad-spectrum semisynthetic cephalosporin antibiotic, is described. These esters were examined as potential orally active antibiotic prodrugs. The superior oral absorption of the three esters relative to the unesterified parent, 1a, is demonstrated by differential blood levels as well as measurement of the rate at which doses of the ester leave the gastrointestinal tract and appear in the urine. A study of the decreased stability of the three esters relative to 1a at pH 4.5, 6.5, and 7.5 is also presented."}
{"id": "PMID:21964", "title": "Some practical results of the London Medical Group conference on iatrogenic disease.", "content": "Although many conferences stimulate a great deal of discussion and practical interest at the time, not so many are followed up to try and estimate what, if any, practical results followed the meeting. This the authors of this study have done. (In Britain the 'medical groups' are voluntary groupings of students at medical schools who meet to discuss ethical problems related to their profession). Sixty-five participants (not all of them students) in the conference on iatrogenic disease replied to the questionnaire, and from the answers it was clear that not only the attitudes of those responding had in some cases been changed but in some positive action had resulted, for example, in the matter of prescribing. This analysis may provide an answer to those who criticize conferences as being a waste of time and money, because much more than could be evaluated from the responses to this survey must have affected all the participants.", "contents": "Some practical results of the London Medical Group conference on iatrogenic disease. Although many conferences stimulate a great deal of discussion and practical interest at the time, not so many are followed up to try and estimate what, if any, practical results followed the meeting. This the authors of this study have done. (In Britain the 'medical groups' are voluntary groupings of students at medical schools who meet to discuss ethical problems related to their profession). Sixty-five participants (not all of them students) in the conference on iatrogenic disease replied to the questionnaire, and from the answers it was clear that not only the attitudes of those responding had in some cases been changed but in some positive action had resulted, for example, in the matter of prescribing. This analysis may provide an answer to those who criticize conferences as being a waste of time and money, because much more than could be evaluated from the responses to this survey must have affected all the participants."}
{"id": "PMID:21966", "title": "Glucose-6-phosphate dehydrogenase (G6PD) activity of human sperm.", "content": "Sperm from normal human donors and a G6PD-A- individual were examined for x-linked glucose-6-phosphate dehydrogenase activity and autosomally linked 6-phosphogluconate dehydrogenase activity. With the use of fluorescence microscopy, we divised a procedure to visualise in individual sperm cells the fluorescence of reduced coenzyme NADPH formed by each of the two enzymes in the presence of appropriate substrates. We found significant differences in the population distribution of sperm expressing each of the two activities, and the ratio of the two activities in sperm homogenate is very different from the one found in erythrocyte lysates. The possibility of haploid gene expression has been considered in interpreting these results.", "contents": "Glucose-6-phosphate dehydrogenase (G6PD) activity of human sperm. Sperm from normal human donors and a G6PD-A- individual were examined for x-linked glucose-6-phosphate dehydrogenase activity and autosomally linked 6-phosphogluconate dehydrogenase activity. With the use of fluorescence microscopy, we divised a procedure to visualise in individual sperm cells the fluorescence of reduced coenzyme NADPH formed by each of the two enzymes in the presence of appropriate substrates. We found significant differences in the population distribution of sperm expressing each of the two activities, and the ratio of the two activities in sperm homogenate is very different from the one found in erythrocyte lysates. The possibility of haploid gene expression has been considered in interpreting these results."}
{"id": "PMID:21967", "title": "Primary care education trends in U.S. medical schools and teaching hospitals.", "content": "In 1973 Schroeder and colleagues conducted a survey of U.S. Medical schools in order to ascertain the nature of change in primary care education which had occurred by that date. In 1976 the authors of the present paper utilized the same survey instrument to document trend data over the three-year period. While conclusions from the 1973 survey pictured primary care education in a transitional state, the 1976 data suggest movement toward a general consolidation of efforts. The 1976 data indicate a continued emphasis on education in the ambulatory care area with no well-defined locus for coordinating institutionwide primary care training efforts, a leveling off of interest in health maintenance organizations (HMO) affiliations, no significant change in the number of affiliated programs for training nurse practitioners or physician's assistants, and a marked increase in the number of schools with affiliated generalist residency programs in internal medicine and pediatrics.", "contents": "Primary care education trends in U.S. medical schools and teaching hospitals. In 1973 Schroeder and colleagues conducted a survey of U.S. Medical schools in order to ascertain the nature of change in primary care education which had occurred by that date. In 1976 the authors of the present paper utilized the same survey instrument to document trend data over the three-year period. While conclusions from the 1973 survey pictured primary care education in a transitional state, the 1976 data suggest movement toward a general consolidation of efforts. The 1976 data indicate a continued emphasis on education in the ambulatory care area with no well-defined locus for coordinating institutionwide primary care training efforts, a leveling off of interest in health maintenance organizations (HMO) affiliations, no significant change in the number of affiliated programs for training nurse practitioners or physician's assistants, and a marked increase in the number of schools with affiliated generalist residency programs in internal medicine and pediatrics."}
{"id": "PMID:21968", "title": "Orientation effects on microwave-induced hyperthermia and neurochemical correlates.", "content": "This paper describes the effect of field orientation on the hyperthermia produced by microwave irradiation. Rats exposed in the E-orientation (long-axis of animal parallel to E-field) to 1600 tmhz radiation become significantly hotter than those exposed in the H-field at the same power density. Norepinephrine and dopamine, but not serotonin content of the basal hypothalamus is reduced as a concomitant of microwave-induced brain hyperthermia.", "contents": "Orientation effects on microwave-induced hyperthermia and neurochemical correlates. This paper describes the effect of field orientation on the hyperthermia produced by microwave irradiation. Rats exposed in the E-orientation (long-axis of animal parallel to E-field) to 1600 tmhz radiation become significantly hotter than those exposed in the H-field at the same power density. Norepinephrine and dopamine, but not serotonin content of the basal hypothalamus is reduced as a concomitant of microwave-induced brain hyperthermia."}
{"id": "PMID:21970", "title": "An electron microscopic study of early developmental stages, myogenesis, oogenesis and cnidogenesis in the anthomedusa, Podocoryne carnea M. Sars.", "content": "This descriptive electron microscopic study of the blastogenetic medusa development of Podocoryne carnea focuses on the earliest stages of primordium formation, myogenesis, oogenesis and cnidogenesis. The events which take place at the cellular level prior to the formation of stage 1 (Frey, '68), which are characterized by ecto- and entodermal accumulations of undifferentiated I-cells and the beginning of transdifferentiation of epithelial cells, have been subdivided into four distinct stages (U1-U4). The genealogy of cells participating in medusa differentiation indicates that some cell types of the medusa are derived by transdifferentiation from the polyp's epithelial cells, while others originate by differentiation from I-cells. The myogenesis of the subumbrellar muscle cells resembles vertebrate myocardiac differentiation in many respects.", "contents": "An electron microscopic study of early developmental stages, myogenesis, oogenesis and cnidogenesis in the anthomedusa, Podocoryne carnea M. Sars. This descriptive electron microscopic study of the blastogenetic medusa development of Podocoryne carnea focuses on the earliest stages of primordium formation, myogenesis, oogenesis and cnidogenesis. The events which take place at the cellular level prior to the formation of stage 1 (Frey, '68), which are characterized by ecto- and entodermal accumulations of undifferentiated I-cells and the beginning of transdifferentiation of epithelial cells, have been subdivided into four distinct stages (U1-U4). The genealogy of cells participating in medusa differentiation indicates that some cell types of the medusa are derived by transdifferentiation from the polyp's epithelial cells, while others originate by differentiation from I-cells. The myogenesis of the subumbrellar muscle cells resembles vertebrate myocardiac differentiation in many respects."}
{"id": "PMID:21972", "title": "Hormonal regulation of testicular descent: experimental and clinical observations.", "content": "Hormonal regulation of testicular descent has been investigated. Based on experimental studies using the rat and on a review of clinical material it has been determined that testicular descent is an androgen-mediated event directly under the regulation of pituitary gonadotropin. Furthermore, the active androgenic metabolite involved in this process appears to be dihydrotestosterone, which is synthesized by the testis and must be present in high local concentrations to be effective. In addition to these hormonal requirements the anatomy of the inguinal canal must provide unimpeded migration of the testis into the scrotum. Any imbalance or anomaly of these prerequisites may lead to cryptorchidism.", "contents": "Hormonal regulation of testicular descent: experimental and clinical observations. Hormonal regulation of testicular descent has been investigated. Based on experimental studies using the rat and on a review of clinical material it has been determined that testicular descent is an androgen-mediated event directly under the regulation of pituitary gonadotropin. Furthermore, the active androgenic metabolite involved in this process appears to be dihydrotestosterone, which is synthesized by the testis and must be present in high local concentrations to be effective. In addition to these hormonal requirements the anatomy of the inguinal canal must provide unimpeded migration of the testis into the scrotum. Any imbalance or anomaly of these prerequisites may lead to cryptorchidism."}
{"id": "PMID:21973", "title": "Protective efficacy of pneumococcal polysaccharide vaccines.", "content": "Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.", "contents": "Protective efficacy of pneumococcal polysaccharide vaccines. Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci."}
{"id": "PMID:21974", "title": "Management of diabetic patients with low blood pH.", "content": "In metabolic acidosis, where blood pH is less than 7.20, loss of respiratory centre response to lowered carbon dioxide content and increased hydrogen ion concentration may result. The use of sodium bicarbonate for management of diabetic ketosis and lactic acidosis has been controversial (Kaye 1975) in the past, but it is now the treatment of choice.", "contents": "Management of diabetic patients with low blood pH. In metabolic acidosis, where blood pH is less than 7.20, loss of respiratory centre response to lowered carbon dioxide content and increased hydrogen ion concentration may result. The use of sodium bicarbonate for management of diabetic ketosis and lactic acidosis has been controversial (Kaye 1975) in the past, but it is now the treatment of choice."}
{"id": "PMID:21981", "title": "Cause of decrease of ethylmorphine N-demethylase activity of lipid peroxidation in microsomes from the rat, guinea pig and rabbit.", "content": "There were marked differences among animal species between NADPH-dependent and ascorbic acid-Fe++-dependent lipid peroxidation. In NADPH-dependent lipid peroxidation, this activity occurred to the greatest extent in rats followed by guinea pigs and rabbits and such was much lower in rabbits than in guinea pigs. On the other hand, rabbit microsomes exhibited higher lipid peroxidation activity than guinea pigs in ascorbic acid plus Fe++ or Fe++-dependent lipid peroxidation although the activity was still lower than in rats. The ascorbic acid plus Fe++-stimulated lipid peroxidation produced a decrease in ethylmorphine N-demethylase activity which was closely related to ethylmorphine-enhanced NADPH-cytochrome P-450 reductase activity but was not related to the change of the apparent content of cytochrome P-450 in all animal species. These results indicate that decrease of NADPH-cytochrome P-450 reductase activity induces a decrease in ethylmorphine N-demethylase activity by lipid peroxidation.", "contents": "Cause of decrease of ethylmorphine N-demethylase activity of lipid peroxidation in microsomes from the rat, guinea pig and rabbit. There were marked differences among animal species between NADPH-dependent and ascorbic acid-Fe++-dependent lipid peroxidation. In NADPH-dependent lipid peroxidation, this activity occurred to the greatest extent in rats followed by guinea pigs and rabbits and such was much lower in rabbits than in guinea pigs. On the other hand, rabbit microsomes exhibited higher lipid peroxidation activity than guinea pigs in ascorbic acid plus Fe++ or Fe++-dependent lipid peroxidation although the activity was still lower than in rats. The ascorbic acid plus Fe++-stimulated lipid peroxidation produced a decrease in ethylmorphine N-demethylase activity which was closely related to ethylmorphine-enhanced NADPH-cytochrome P-450 reductase activity but was not related to the change of the apparent content of cytochrome P-450 in all animal species. These results indicate that decrease of NADPH-cytochrome P-450 reductase activity induces a decrease in ethylmorphine N-demethylase activity by lipid peroxidation."}
{"id": "PMID:21982", "title": "Dualist or pseudo-dualist interactions of mepyramine, diphenhydramine and eprozinol with histamine at H1-receptors.", "content": "The types of interaction of mepyramine (M), diphenhydramin: (D) and eprozinol (E), with histamine H1-receptors of guinea pig ileal and tracheal smooth muscle, were comparatively studied in vitro. According to the concentrations used, all three substances showed an apparent dualist mechanism of action on both preparations when histamine (dihydrochloride) was used as the agonist. The competitive component of this mechanism (at low concentrations) was characterized by the following pA2 values: 9.01 (M), 7.80 (D) and 5.64 (E) with the ileum; 8.06 (M), 7.00 (D) and 6.02 (E) with the trachea. The so called non specific component (at high concentrations) was of comparable intensity in the two organs. The pD'2 values were 5.54-5.66 (M), 4.65-4.38 (D) and 3.82-3.55 (E) with ileal and tracheal muscle, respectively. At low concentrations the equi-active dose-ratio for N/D/E (1/16/2300 on the ileum) became 1/12/110 when the trachea was used as the effector. This is surprising since histaminergic receptors of the two preparations are of the same H1-type. It is suggested that only diphenhydramine and eprozinol are really dualistic, and that the non-specific mechanism of activity differs for each drug with that of eprozinol being effective on tracheal muscle.", "contents": "Dualist or pseudo-dualist interactions of mepyramine, diphenhydramine and eprozinol with histamine at H1-receptors. The types of interaction of mepyramine (M), diphenhydramin: (D) and eprozinol (E), with histamine H1-receptors of guinea pig ileal and tracheal smooth muscle, were comparatively studied in vitro. According to the concentrations used, all three substances showed an apparent dualist mechanism of action on both preparations when histamine (dihydrochloride) was used as the agonist. The competitive component of this mechanism (at low concentrations) was characterized by the following pA2 values: 9.01 (M), 7.80 (D) and 5.64 (E) with the ileum; 8.06 (M), 7.00 (D) and 6.02 (E) with the trachea. The so called non specific component (at high concentrations) was of comparable intensity in the two organs. The pD'2 values were 5.54-5.66 (M), 4.65-4.38 (D) and 3.82-3.55 (E) with ileal and tracheal muscle, respectively. At low concentrations the equi-active dose-ratio for N/D/E (1/16/2300 on the ileum) became 1/12/110 when the trachea was used as the effector. This is surprising since histaminergic receptors of the two preparations are of the same H1-type. It is suggested that only diphenhydramine and eprozinol are really dualistic, and that the non-specific mechanism of activity differs for each drug with that of eprozinol being effective on tracheal muscle."}
{"id": "PMID:21983", "title": "Norepinephrine-synthesizing enzymes in brain, adrenals and peripheral sympathetic nerves of spontaneously hypertensive rats.", "content": "Dopamine-beta-hydroxylase (DBH) activity in serum, DBH and tyrosine hydroxylase (TH) activities in mesenteric vessels, and DBH and TH activities in locus coeruleus and hypothalamus of brain did not differ significantly between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR) at 16 weeks of age when hypertension of SHR was fixed. In contrast, DBH and TH activities in vas deferens and adrenal glands were significantly higher in SHR than in WKR. These changes in SHR at 16 weeks of age after establishment of hypertension are directly opposite those reported previously in SHR at 3 weeks of age before the onset of hypertension.", "contents": "Norepinephrine-synthesizing enzymes in brain, adrenals and peripheral sympathetic nerves of spontaneously hypertensive rats. Dopamine-beta-hydroxylase (DBH) activity in serum, DBH and tyrosine hydroxylase (TH) activities in mesenteric vessels, and DBH and TH activities in locus coeruleus and hypothalamus of brain did not differ significantly between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR) at 16 weeks of age when hypertension of SHR was fixed. In contrast, DBH and TH activities in vas deferens and adrenal glands were significantly higher in SHR than in WKR. These changes in SHR at 16 weeks of age after establishment of hypertension are directly opposite those reported previously in SHR at 3 weeks of age before the onset of hypertension."}
{"id": "PMID:21992", "title": "The action of antacids on serum gastrin concentrations in man.", "content": "The effects of two doses of NaCl and NaHCO3 as well as of Al(OH3) and AlCl3 respectively, on serum gastrin concentrations and intragastric pH were compared in duodenal ulcer patients. Also the effect of one dose of an AlPO4 containing commercial antacid on serum gastrin concentration and intragastric pH was studied in duodenal ulcer patients and in a control group. Care was taken to induce swallowing at the times the substances were given through an orogastric tube. The study showed that antacids elicited significantly greater gastrin responses than their non-buffering chloride compounds and that the rise of gastrin after a single dose of antacid was small but significant in duodenal ulcer patients and insignificant in non-ulcer controls. Several factors as rising intragastric pH, individual responsiveness, duodenal ulcer state, vagal influences, the participating ions and their amount contribute to the rise of gastrin after antacids.", "contents": "The action of antacids on serum gastrin concentrations in man. The effects of two doses of NaCl and NaHCO3 as well as of Al(OH3) and AlCl3 respectively, on serum gastrin concentrations and intragastric pH were compared in duodenal ulcer patients. Also the effect of one dose of an AlPO4 containing commercial antacid on serum gastrin concentration and intragastric pH was studied in duodenal ulcer patients and in a control group. Care was taken to induce swallowing at the times the substances were given through an orogastric tube. The study showed that antacids elicited significantly greater gastrin responses than their non-buffering chloride compounds and that the rise of gastrin after a single dose of antacid was small but significant in duodenal ulcer patients and insignificant in non-ulcer controls. Several factors as rising intragastric pH, individual responsiveness, duodenal ulcer state, vagal influences, the participating ions and their amount contribute to the rise of gastrin after antacids."}
{"id": "PMID:21999", "title": "Pleural effusions.", "content": "Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack.", "contents": "Pleural effusions. Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack."}
{"id": "PMID:21998", "title": "Alterations in tyrosine aminotransferase isoenzymes of liver of rats as a function of age.", "content": "The specific activities (units/mg protein) of tyrosine aminotransferase (TAT) and its isoenzymes, cytoplasmic (c-), mitochondrial (m-) and nuclear (n-TAT), of the liver of 6-, 35- and 76-week old male albino rats were determined. The activities of all the isoenzymes are highest at 6 weeks and are significantly lower at 35 weeks. Total TAT and c-TAT remain unchanged, m-TAT decreases and n-TAT increases significantly after 35 weeks. c-TAT was partially purified from the liver of rats of the three ages to study its kinetic and molecular properties. These properties apparently do not change as a function of age.", "contents": "Alterations in tyrosine aminotransferase isoenzymes of liver of rats as a function of age. The specific activities (units/mg protein) of tyrosine aminotransferase (TAT) and its isoenzymes, cytoplasmic (c-), mitochondrial (m-) and nuclear (n-TAT), of the liver of 6-, 35- and 76-week old male albino rats were determined. The activities of all the isoenzymes are highest at 6 weeks and are significantly lower at 35 weeks. Total TAT and c-TAT remain unchanged, m-TAT decreases and n-TAT increases significantly after 35 weeks. c-TAT was partially purified from the liver of rats of the three ages to study its kinetic and molecular properties. These properties apparently do not change as a function of age."}
{"id": "PMID:22033", "title": "Effectors of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver.", "content": "The lower Vmax of 6PGDH with respect to G6PDH and its higher sensitivity to inhibition by NADPH, suggest the existence of an imbalance between the two dehydrogenases of the pentose phosphate pathway in rat liver. Possible modulators of these activities, particularly in relation with the inhibition by NADPH in physiological conditions, have been investigated. The results suggest that in both cases the inhibition by NADPH is strictly isosteric and that the relative affinities for the reduced and oxidized forms of the pyridine nucleotide are unaffected by glutathion, the intermediates of the pentose phosphate shunt or some divalent ions.", "contents": "Effectors of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. The lower Vmax of 6PGDH with respect to G6PDH and its higher sensitivity to inhibition by NADPH, suggest the existence of an imbalance between the two dehydrogenases of the pentose phosphate pathway in rat liver. Possible modulators of these activities, particularly in relation with the inhibition by NADPH in physiological conditions, have been investigated. The results suggest that in both cases the inhibition by NADPH is strictly isosteric and that the relative affinities for the reduced and oxidized forms of the pyridine nucleotide are unaffected by glutathion, the intermediates of the pentose phosphate shunt or some divalent ions."}
{"id": "PMID:22034", "title": "Isocitrate dehydrogenase of Tetrahymena pyriformis.", "content": "We have studied the isocitrate dehydrogenase of Tetrahymena pyriformis. This enzyme is able to utilize both NAD and NADP, but kinetic studies suggest that the enzymatic activity with NAD is not of physiological signifance. Some of the factors that might regualte the NADP-dependent isocitrate dehydrogenase were also studied. This enzyme has an absolute requirement for divalent cations; Mg,+ and Mn2+ will serve as cofactors but the latter is more effective than the former. It is known that this enzyme is subject to a concerted inhibition by oxaloacetate and glyoxylate. Either glyoxylate or oxaloacetate alone also are capable of inhibiting the enzyme although higher concentrations are required. We have found concerted inhibition also for the NAD-dependent isocitrate dehydrogenase from rat liver and yeast. The activity of the Tetrahymena pyriformis enzyme is inhibited by NADPH. This inhibition is competitive with NADP. The Ki and Km values are, respectively, 20 micrometers and 18 micrometers.", "contents": "Isocitrate dehydrogenase of Tetrahymena pyriformis. We have studied the isocitrate dehydrogenase of Tetrahymena pyriformis. This enzyme is able to utilize both NAD and NADP, but kinetic studies suggest that the enzymatic activity with NAD is not of physiological signifance. Some of the factors that might regualte the NADP-dependent isocitrate dehydrogenase were also studied. This enzyme has an absolute requirement for divalent cations; Mg,+ and Mn2+ will serve as cofactors but the latter is more effective than the former. It is known that this enzyme is subject to a concerted inhibition by oxaloacetate and glyoxylate. Either glyoxylate or oxaloacetate alone also are capable of inhibiting the enzyme although higher concentrations are required. We have found concerted inhibition also for the NAD-dependent isocitrate dehydrogenase from rat liver and yeast. The activity of the Tetrahymena pyriformis enzyme is inhibited by NADPH. This inhibition is competitive with NADP. The Ki and Km values are, respectively, 20 micrometers and 18 micrometers."}
{"id": "PMID:22035", "title": "[The legal status of medical students during practical training in hospitals (author's transl)].", "content": "The most important change in the qualification regulations in force at the present time is the provision for the practical training of medical students, which occurs not only in university hospitals but also in \"teaching hospitals\" outside the university. The realization of the practical year is problematic according to the actual conditions because of the difficulties and financial investment necessarily associated with it. Furthermore, the legal status of the students during the practical activities differes from that of earlier medical assistants, because according to the present law the legal provisions for employment and social insurance such as the determination of division of labour, working hours and remuneration and also for third party and accident insurance do not apply.", "contents": "[The legal status of medical students during practical training in hospitals (author's transl)]. The most important change in the qualification regulations in force at the present time is the provision for the practical training of medical students, which occurs not only in university hospitals but also in \"teaching hospitals\" outside the university. The realization of the practical year is problematic according to the actual conditions because of the difficulties and financial investment necessarily associated with it. Furthermore, the legal status of the students during the practical activities differes from that of earlier medical assistants, because according to the present law the legal provisions for employment and social insurance such as the determination of division of labour, working hours and remuneration and also for third party and accident insurance do not apply."}
{"id": "PMID:22036", "title": "[Hyperergic collagenoses. Clinical aspects, differential diagnosis and therapy (author's transl)].", "content": "On the basis of inpatient and outpatient observations of the longterm course in 44 patients with erythematodes disseminatus, 8 with periarteritis nodosa, 4 with Wegener's granulomatosis, 5 with dermatomyositis, 3 with giant cell arteritis and 9 with scleroderma the pathogenesis, differential diagnosis and therapy of these diseases is discussed. The differential diagnosis and longterm supervision being dealt with particularly thoroughly. Early recognition of the disease episodes and appropriate therapeutic action in the shape of increased doses of prednisolone are important. Additional cytostatics were given if the kidney was involved.", "contents": "[Hyperergic collagenoses. Clinical aspects, differential diagnosis and therapy (author's transl)]. On the basis of inpatient and outpatient observations of the longterm course in 44 patients with erythematodes disseminatus, 8 with periarteritis nodosa, 4 with Wegener's granulomatosis, 5 with dermatomyositis, 3 with giant cell arteritis and 9 with scleroderma the pathogenesis, differential diagnosis and therapy of these diseases is discussed. The differential diagnosis and longterm supervision being dealt with particularly thoroughly. Early recognition of the disease episodes and appropriate therapeutic action in the shape of increased doses of prednisolone are important. Additional cytostatics were given if the kidney was involved."}
{"id": "PMID:22042", "title": "Factors influencing germ tube production in Candida albicans.", "content": "The capacity of Candida albicans to produce germ tubes in a simple medium is analysed as a function of the pH variation, the bacterial supernatant and the addition of differing concentrations of various species of bacteria.", "contents": "Factors influencing germ tube production in Candida albicans. The capacity of Candida albicans to produce germ tubes in a simple medium is analysed as a function of the pH variation, the bacterial supernatant and the addition of differing concentrations of various species of bacteria."}
{"id": "PMID:22043", "title": "Determinations of pH, moisture, carbohydrates and ash of Egyptian buffalo meat.", "content": "A total of 128 samples of Egyptian buffalo meat was analysed for its pH value, moisture, carbohydrates and ash contents. Statistical analysis of the data obtained shows significant difference at 0.01 level for moisture in relation to sex and cut (abdomen and thigh, respectively). There is also significant difference at 0.05 level for moisture in dry season in relation to sex and for ash in relation to cut. At 0.1 level moisture shows a significant difference in relation to season, female in relation to season and green season in relation to sex. Ash also shows a significant difference at 0.1 level in female in relation to season.", "contents": "Determinations of pH, moisture, carbohydrates and ash of Egyptian buffalo meat. A total of 128 samples of Egyptian buffalo meat was analysed for its pH value, moisture, carbohydrates and ash contents. Statistical analysis of the data obtained shows significant difference at 0.01 level for moisture in relation to sex and cut (abdomen and thigh, respectively). There is also significant difference at 0.05 level for moisture in dry season in relation to sex and for ash in relation to cut. At 0.1 level moisture shows a significant difference in relation to season, female in relation to season and green season in relation to sex. Ash also shows a significant difference at 0.1 level in female in relation to season."}
{"id": "PMID:22044", "title": "[Alkali treatment of proteins. I. Behavior of sulfhydryl and disulfide groups in alkali-treated beta-lactoglobulin and alpha-lactalbumin].", "content": "The alkali treatment of beta-lactoglobulin and alpha-lactalbumin results in the splitting of disulphide bonds in the protein molecules. When a 0.8-10(4) M beta-lactoglobulin solution in a 0.022 N sodium hydroxide solution (pH = 12) is heated at 90 degrees C for 30 min, 0-4 M disulphide groups, 2.2 M sulfhydryl groups and 1.8 M sulphide ions/M dimeric beta-lactoglobulin are detectable of the total of 4 M disulphide groups and 2 M sulfhydryl groups/M dimeric beta-lactoglobulin. The sulphide ions can be determined directly in the form of hydrogen sulphide or by calculating the difference between the values from the amperometric-argentometric titration and those from the method of ELLMAN (reaction with DTNB). The disulphide groups are determined with the aid of DTNB after reduction with sodium borohydride. The sulfhydryl groups obtained by reduction with sodium borohydride re-oxidize, the reaction velocity being of the second order. If the disulphide groups are reduced with sodium borohydride, the argentometric-amperometric determination of the sulfhydryl groups by means of the platinum rotating-disk electrode is disturbed by the presence of boric acid.", "contents": "[Alkali treatment of proteins. I. Behavior of sulfhydryl and disulfide groups in alkali-treated beta-lactoglobulin and alpha-lactalbumin]. The alkali treatment of beta-lactoglobulin and alpha-lactalbumin results in the splitting of disulphide bonds in the protein molecules. When a 0.8-10(4) M beta-lactoglobulin solution in a 0.022 N sodium hydroxide solution (pH = 12) is heated at 90 degrees C for 30 min, 0-4 M disulphide groups, 2.2 M sulfhydryl groups and 1.8 M sulphide ions/M dimeric beta-lactoglobulin are detectable of the total of 4 M disulphide groups and 2 M sulfhydryl groups/M dimeric beta-lactoglobulin. The sulphide ions can be determined directly in the form of hydrogen sulphide or by calculating the difference between the values from the amperometric-argentometric titration and those from the method of ELLMAN (reaction with DTNB). The disulphide groups are determined with the aid of DTNB after reduction with sodium borohydride. The sulfhydryl groups obtained by reduction with sodium borohydride re-oxidize, the reaction velocity being of the second order. If the disulphide groups are reduced with sodium borohydride, the argentometric-amperometric determination of the sulfhydryl groups by means of the platinum rotating-disk electrode is disturbed by the presence of boric acid."}
{"id": "PMID:22049", "title": "Neurotransmitter synthesis and uptake by isolated sympathetic neurones in microcultures.", "content": "Assays of isolated single sympathetic neurones show that their transmitter functions can be either adrenergic or cholinergic depending on growth conditions. The data suggest that the number of transmitters made by most mature individual neurones is restricted.", "contents": "Neurotransmitter synthesis and uptake by isolated sympathetic neurones in microcultures. Assays of isolated single sympathetic neurones show that their transmitter functions can be either adrenergic or cholinergic depending on growth conditions. The data suggest that the number of transmitters made by most mature individual neurones is restricted."}
{"id": "PMID:22051", "title": "The influence of pH on the excision of UV-photoproducts from HeLa cells.", "content": "Excision of pyrimidine dimers with pH decreasing in UV irradiated HeLa cells can be depressed. This depression is independent of the UV dose within the investigated range. The excision capacity of HeLa repair system from absolute amount of excised dimers is shown.", "contents": "The influence of pH on the excision of UV-photoproducts from HeLa cells. Excision of pyrimidine dimers with pH decreasing in UV irradiated HeLa cells can be depressed. This depression is independent of the UV dose within the investigated range. The excision capacity of HeLa repair system from absolute amount of excised dimers is shown."}
{"id": "PMID:22053", "title": "Local glucose utilization in acute focal cerebral ischemia: local dysmetabolism and diaschisis.", "content": "By means of an autoradiographic technique employing 14C-2-deoxyglucose, abnormalities of local brain glucose utilization were studied 90 minutes following occlusion of the left middle cerebral and common carotid arteries in a series of pentobarbital-anesthetized cats. Sham-insulted control animals exhibited a normal pattern of regional glucose utilization. In animals with vascular occlusion, a zone of greatly suppressed glucose utilization occupied the caudate nucleus of the ischemic hemisphere, with variable extension, and was surrounded by a narrow rim of increased local brain glucose utilization, suggesting the occurrence of enhanced anaerobic glycolysis in the latter zones. The cerebral cortex, which was less constantly affected, showed alternating regions of increased and decreased glucose utilization. Quantitation of local brain glucose utilization values from the contralateral nonischemic hemisphere revealed a mild suppression of cortical glucose utilization relative to the control animals. This may be the metabolic equivalent of diaschisis.", "contents": "Local glucose utilization in acute focal cerebral ischemia: local dysmetabolism and diaschisis. By means of an autoradiographic technique employing 14C-2-deoxyglucose, abnormalities of local brain glucose utilization were studied 90 minutes following occlusion of the left middle cerebral and common carotid arteries in a series of pentobarbital-anesthetized cats. Sham-insulted control animals exhibited a normal pattern of regional glucose utilization. In animals with vascular occlusion, a zone of greatly suppressed glucose utilization occupied the caudate nucleus of the ischemic hemisphere, with variable extension, and was surrounded by a narrow rim of increased local brain glucose utilization, suggesting the occurrence of enhanced anaerobic glycolysis in the latter zones. The cerebral cortex, which was less constantly affected, showed alternating regions of increased and decreased glucose utilization. Quantitation of local brain glucose utilization values from the contralateral nonischemic hemisphere revealed a mild suppression of cortical glucose utilization relative to the control animals. This may be the metabolic equivalent of diaschisis."}
{"id": "PMID:22057", "title": "Significance of oscillation frequency in intrapartum fetal monitoring.", "content": "Until now, no statistical data have been available on the significance of the frequency of FHR oscillations. In order to evaluate the relation between oscillation frequency and neonatal outcome, the last 30 minutes of 812 FHR records were analyzed with respect to the number of 812 FHR records were analyzed with respect to the number of oscillations per minute only. Close correlations were found between slow oscillations below 2 per minute and the arterial cord pH as well as the Apgar scores after 1 and 5 minutes, respectively. No relation could be established between any oscillation frequency above 2 per minute and the measures of the neonatal outcome. In discussing the results, slow oscillations are suggested to be identical with the sinusoidal FHR. Emphasis is made that for an appropriate pattern recognition, true beat-to-beat recording is required, avoiding any averaging procedure.", "contents": "Significance of oscillation frequency in intrapartum fetal monitoring. Until now, no statistical data have been available on the significance of the frequency of FHR oscillations. In order to evaluate the relation between oscillation frequency and neonatal outcome, the last 30 minutes of 812 FHR records were analyzed with respect to the number of 812 FHR records were analyzed with respect to the number of oscillations per minute only. Close correlations were found between slow oscillations below 2 per minute and the arterial cord pH as well as the Apgar scores after 1 and 5 minutes, respectively. No relation could be established between any oscillation frequency above 2 per minute and the measures of the neonatal outcome. In discussing the results, slow oscillations are suggested to be identical with the sinusoidal FHR. Emphasis is made that for an appropriate pattern recognition, true beat-to-beat recording is required, avoiding any averaging procedure."}
{"id": "PMID:22058", "title": "Hyaline membrane disease and acidosis at birth in twins.", "content": "To test the hypothesis that the increased incidence of hyaline membrane disease in second-born twins is related to acidosis at birth, umbilical arterial [H+] was measured in 26 sets of premature twins. Although overall Twin B had a lower Apgar score than Twin A, there was no difference in their [H+]. If the delivery interval was prolonged over 8 minutes then Twin B infants were more acidemic and had lower Apgar scores. Infants with hyaline membrane disease had lower Apgar scores, but were not more acidemic than infants without respiratory distress. Our data suggest that acidosis at birth is not an important factor in the development of hyaline membrane disease.", "contents": "Hyaline membrane disease and acidosis at birth in twins. To test the hypothesis that the increased incidence of hyaline membrane disease in second-born twins is related to acidosis at birth, umbilical arterial [H+] was measured in 26 sets of premature twins. Although overall Twin B had a lower Apgar score than Twin A, there was no difference in their [H+]. If the delivery interval was prolonged over 8 minutes then Twin B infants were more acidemic and had lower Apgar scores. Infants with hyaline membrane disease had lower Apgar scores, but were not more acidemic than infants without respiratory distress. Our data suggest that acidosis at birth is not an important factor in the development of hyaline membrane disease."}
{"id": "PMID:22060", "title": "Serotonin-containing neurons: their possible role in pain and analgesia.", "content": "Experimental evidence is reviewed showing that brain and spinal cord serotonergic neurons are involved in nociceptive responses, as well as in the analgesic effects of opiate narcotics. This evidence, based on studies employing pharmacological, surgical, electrophysiological, and dietary manipulations of central nervous system serotonergic neurotransmission, suggests that increases in the activity of brain and spinal cord serotonin neurons are associated with analgesia and enhanced antinociceptive drug potency, whereas decreases in the activities of these neurons correlate with hyperalgesia and diminished analgesic drug potency.", "contents": "Serotonin-containing neurons: their possible role in pain and analgesia. Experimental evidence is reviewed showing that brain and spinal cord serotonergic neurons are involved in nociceptive responses, as well as in the analgesic effects of opiate narcotics. This evidence, based on studies employing pharmacological, surgical, electrophysiological, and dietary manipulations of central nervous system serotonergic neurotransmission, suggests that increases in the activity of brain and spinal cord serotonin neurons are associated with analgesia and enhanced antinociceptive drug potency, whereas decreases in the activities of these neurons correlate with hyperalgesia and diminished analgesic drug potency."}
{"id": "PMID:22063", "title": "Bicarbonate-induced phosphaturia: Dependence upon the magnitude of phosphate reabsorption.", "content": "The acute effect of bicarbonate infusion on inorganic phsophate (Pi) reabsorption was determined in thyroparathyroidectomized (TPTX) rats stabilized on a high phsophorus diet. In the normophosphatemic state, bicarbonate did not affect Pi reabsorption significantly. On the other hand, after hyperphosphatemia was induced by phosphate loading, bicarbonate inhibited Pi reabsorption. In order to determin if eht aboslute level of plasma or filtered Pi was an improtant determinant of this phosphaturic action of bicarbonate during hyperphosphatemia, equivalent rates of Pi reabsorption were achieved after phosphate infusion in TPTX rats previously stabilized on a low dietary phosphorus intake, but at significantly lower plasma Pi concentrations and filtered Pi loads than in their high dietary phosphorus counterparts. Bicarbonate inhibited Pi reabsorption equivalently in both hyperphosphatemic groups, indicating that the magnitude of Pi transport itself was of importance in determining the inhibitory response to bicarbonate. In addition, the results suggest that transport mechanisms for bicarbonate and Pi may interact competitively.", "contents": "Bicarbonate-induced phosphaturia: Dependence upon the magnitude of phosphate reabsorption. The acute effect of bicarbonate infusion on inorganic phsophate (Pi) reabsorption was determined in thyroparathyroidectomized (TPTX) rats stabilized on a high phsophorus diet. In the normophosphatemic state, bicarbonate did not affect Pi reabsorption significantly. On the other hand, after hyperphosphatemia was induced by phosphate loading, bicarbonate inhibited Pi reabsorption. In order to determin if eht aboslute level of plasma or filtered Pi was an improtant determinant of this phosphaturic action of bicarbonate during hyperphosphatemia, equivalent rates of Pi reabsorption were achieved after phosphate infusion in TPTX rats previously stabilized on a low dietary phosphorus intake, but at significantly lower plasma Pi concentrations and filtered Pi loads than in their high dietary phosphorus counterparts. Bicarbonate inhibited Pi reabsorption equivalently in both hyperphosphatemic groups, indicating that the magnitude of Pi transport itself was of importance in determining the inhibitory response to bicarbonate. In addition, the results suggest that transport mechanisms for bicarbonate and Pi may interact competitively."}
{"id": "PMID:22069", "title": "Reversible lactic acidosis associated with repeated intravenous infusions of sorbitol and ethanol.", "content": "Infusions of fructose or sorbitol are used commonly in parenteral nutrition and may cause lactic acidosis. A case is reported in whom blood lactate concentration was monitored frequently over a 5-day period during intravenous feeding with a sorbitol-ethanol-amino acid mixture. During the first five infusions blood lactate rose only moderately, but with the final infusion lactate rose to 11-1 mmol/l and the patient had a severe metabolic acidosis. In retrospect the patient had shown deterioration in renal and hepatic function tests during the preceding 24 hr. On terminating the infusions the blood lactate concentration fell rapidly. It is suggested that great care should be exercised when using such infusions in ill patients and acid base status and renal and hepatic function should be monitored frequently.", "contents": "Reversible lactic acidosis associated with repeated intravenous infusions of sorbitol and ethanol. Infusions of fructose or sorbitol are used commonly in parenteral nutrition and may cause lactic acidosis. A case is reported in whom blood lactate concentration was monitored frequently over a 5-day period during intravenous feeding with a sorbitol-ethanol-amino acid mixture. During the first five infusions blood lactate rose only moderately, but with the final infusion lactate rose to 11-1 mmol/l and the patient had a severe metabolic acidosis. In retrospect the patient had shown deterioration in renal and hepatic function tests during the preceding 24 hr. On terminating the infusions the blood lactate concentration fell rapidly. It is suggested that great care should be exercised when using such infusions in ill patients and acid base status and renal and hepatic function should be monitored frequently."}
{"id": "PMID:22075", "title": "Unfolding and refolding occur much faster for a proline-free proteins than for most proline-containing proteins.", "content": "The kinetics for unfolding and refolding of a parvalbumin (band 5) have been examined as a function of pH near the transition region, using stopped-flow techniques. This protein is rather unusual in that it has no proline residues, and therefore serves as a good example to test the hypothesis that the rate-limiting step seen in denaturation reactions is due to the cis-trans isomerization of proline peptide bonds in the denatured state. The kinetics for parvalbumin unfolding and refolding are complex, with the data being resolvable into two fast phases at 25 degrees. The slower of the two phases seen for the parvalbumin is about 100 to 500 times faster than the slow phase seen for proline-containing proteins under the same conditions! These results argue strongly in support of the proline isomerization hypothesis. It is also suggested that the slower phase seen for parvalbumin and the second-slowest phase seen for proline-containing proteins might be due to the cis-trans isomerization of peptide bonds of non-proline residues.", "contents": "Unfolding and refolding occur much faster for a proline-free proteins than for most proline-containing proteins. The kinetics for unfolding and refolding of a parvalbumin (band 5) have been examined as a function of pH near the transition region, using stopped-flow techniques. This protein is rather unusual in that it has no proline residues, and therefore serves as a good example to test the hypothesis that the rate-limiting step seen in denaturation reactions is due to the cis-trans isomerization of proline peptide bonds in the denatured state. The kinetics for parvalbumin unfolding and refolding are complex, with the data being resolvable into two fast phases at 25 degrees. The slower of the two phases seen for the parvalbumin is about 100 to 500 times faster than the slow phase seen for proline-containing proteins under the same conditions! These results argue strongly in support of the proline isomerization hypothesis. It is also suggested that the slower phase seen for parvalbumin and the second-slowest phase seen for proline-containing proteins might be due to the cis-trans isomerization of peptide bonds of non-proline residues."}
{"id": "PMID:22076", "title": "Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells.", "content": "The effects of dopaminergic agonists and antagonists have been studied in dispersed bovine parathyroid cells. Dopaminergic agonists caused a transient 20- to 40-fold increase in cellular cyclic AMP and a 2- to 3-fold increase in parathyroid hormone release. Dose-response relationships were similar for cyclic AMP accumulation and hormone release, whether studied by increasing agonist concentration or by increasing concentration of antagonist with constant agonist. The effects on the dopamine receptor could be differentiated from those of the previously characterized beta-adrenergic receptor by specific inhibitors. These results appear to represent proof with a homogeneous cell population that dopaminergic receptors linked to adenylate cyclase can regulate a secretory process mediated by cyclic AMP. This system should be useful in further studies on dopamine receptors and should provide a valid tool for determining interactions of radiolabeled ligands with such receptors.", "contents": "Dopaminergic stimulation of cyclic AMP accumulation and parathyroid hormone release from dispersed bovine parathyroid cells. The effects of dopaminergic agonists and antagonists have been studied in dispersed bovine parathyroid cells. Dopaminergic agonists caused a transient 20- to 40-fold increase in cellular cyclic AMP and a 2- to 3-fold increase in parathyroid hormone release. Dose-response relationships were similar for cyclic AMP accumulation and hormone release, whether studied by increasing agonist concentration or by increasing concentration of antagonist with constant agonist. The effects on the dopamine receptor could be differentiated from those of the previously characterized beta-adrenergic receptor by specific inhibitors. These results appear to represent proof with a homogeneous cell population that dopaminergic receptors linked to adenylate cyclase can regulate a secretory process mediated by cyclic AMP. This system should be useful in further studies on dopamine receptors and should provide a valid tool for determining interactions of radiolabeled ligands with such receptors."}
{"id": "PMID:22074", "title": "[Comparative evaluation of the effect of serotonin, melatonin and methoxytryptamine on the content of biogenic amines in the hypothalamus and gonadotropic hormones in the pituitary gland depending on the periodicity of phases of the estrous cycle in rats].", "content": "This work is experimental and devoted to the study of functional activity of the pineal gland. The influence of the main biologically active substances (serotonin, melatonin, mexamin) produced by the epiphysis, on the hypothalamo-hypophysial structures was studied; results pointed to the significant role played by the epiphysis in the neuroendocrine regulation system.", "contents": "[Comparative evaluation of the effect of serotonin, melatonin and methoxytryptamine on the content of biogenic amines in the hypothalamus and gonadotropic hormones in the pituitary gland depending on the periodicity of phases of the estrous cycle in rats]. This work is experimental and devoted to the study of functional activity of the pineal gland. The influence of the main biologically active substances (serotonin, melatonin, mexamin) produced by the epiphysis, on the hypothalamo-hypophysial structures was studied; results pointed to the significant role played by the epiphysis in the neuroendocrine regulation system."}
{"id": "PMID:22077", "title": "Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation.", "content": "Partially purified soluble rat liver guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] was activated by superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1). This activation was prevented with KCN or glutathione, inhibitors of superoxide dismutase. Guanylate cyclase preparations formed superoxide ion. Activation by superoxide dismutase was further enhanced by the addition of nitrate reductase. Although guanylate cyclase activity was much greater with Mn2+ than with Mg2+ as sole cation cofactor, activation with superoxide dismutase was not observed when Mn2+ was included in incubations. Catalase also decreased the activation induced with superoxide dismutase. Thus, activation required the formation of both superoxide ion and H2O2 in incubations. Activation of guanylate cyclase could not be achieved by the addition of H2O2 alone. Scavengers of hydroxyl radicals prevented the activation. It is proposed that superoxide ion and hydrogen peroxide can lead to the formation of hydroxyl radicals that activate guanylate cyclase. This mechanism of activation can explain numerous observations of altered guanylate cyclase activity and cyclic GMP accumulation in tissues with oxidizing and reducing agents. This mechanism will also permit physiological regulation of guanylate cyclase and cyclic GMP formation when there is altered redox or free radical formation in tissues in response to hormones, other agents, and processes.", "contents": "Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation. Partially purified soluble rat liver guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] was activated by superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1). This activation was prevented with KCN or glutathione, inhibitors of superoxide dismutase. Guanylate cyclase preparations formed superoxide ion. Activation by superoxide dismutase was further enhanced by the addition of nitrate reductase. Although guanylate cyclase activity was much greater with Mn2+ than with Mg2+ as sole cation cofactor, activation with superoxide dismutase was not observed when Mn2+ was included in incubations. Catalase also decreased the activation induced with superoxide dismutase. Thus, activation required the formation of both superoxide ion and H2O2 in incubations. Activation of guanylate cyclase could not be achieved by the addition of H2O2 alone. Scavengers of hydroxyl radicals prevented the activation. It is proposed that superoxide ion and hydrogen peroxide can lead to the formation of hydroxyl radicals that activate guanylate cyclase. This mechanism of activation can explain numerous observations of altered guanylate cyclase activity and cyclic GMP accumulation in tissues with oxidizing and reducing agents. This mechanism will also permit physiological regulation of guanylate cyclase and cyclic GMP formation when there is altered redox or free radical formation in tissues in response to hormones, other agents, and processes."}
{"id": "PMID:22078", "title": "Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells.", "content": "The release of slow reacting substance (SRS) from rat basophilic leukemia cells (RBL-1) by the ionophore A23187 (5-10 mug/ml) was stimulated 5-fold by arachidonate and inhibited 78% by 5,8,11,14-eicosatetraynoate (an inhibitor of both fatty acid cyclooxygenase and lipoxygenase). Linoleic acid and linolenic acid both inhibited SRS formation, whereas indomethacin (a cyclooxygenase inhibitor) had no effect. Radiolabel from [14C]- or [3H]arachidonate was incorporated into SRS as indicated by comigration of radioactivity and bioreactivity in several chromatographic systems after purification to apparent radiochemical homogeneity. The radiolabeled SRS was clearly separated chromatographically from other known arachidonate metabolites. Thus, SRS appears to be a previously undescribed product of arachidonic acid metabolism, probably formed through the lipoxygenase pathway. The ability to prepare purified, biosynthetically labeled, SRS should be of considerable help in further studies of its structure, biologic function, and catabolism.", "contents": "Precursor role of arachidonic acid in release of slow reacting substance from rat basophilic leukemia cells. The release of slow reacting substance (SRS) from rat basophilic leukemia cells (RBL-1) by the ionophore A23187 (5-10 mug/ml) was stimulated 5-fold by arachidonate and inhibited 78% by 5,8,11,14-eicosatetraynoate (an inhibitor of both fatty acid cyclooxygenase and lipoxygenase). Linoleic acid and linolenic acid both inhibited SRS formation, whereas indomethacin (a cyclooxygenase inhibitor) had no effect. Radiolabel from [14C]- or [3H]arachidonate was incorporated into SRS as indicated by comigration of radioactivity and bioreactivity in several chromatographic systems after purification to apparent radiochemical homogeneity. The radiolabeled SRS was clearly separated chromatographically from other known arachidonate metabolites. Thus, SRS appears to be a previously undescribed product of arachidonic acid metabolism, probably formed through the lipoxygenase pathway. The ability to prepare purified, biosynthetically labeled, SRS should be of considerable help in further studies of its structure, biologic function, and catabolism."}
{"id": "PMID:22079", "title": "Human leukocytic pyrogen: purification and development of a radioimmunoassay.", "content": "Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans.", "contents": "Human leukocytic pyrogen: purification and development of a radioimmunoassay. Leukocytic pyrogen is a small endogenous protein that mediates fever. Because of the limitations of bioassays, circulating leukocytic pyrogen has not been demonstrated during fever in humans. The pyrogen was produced in vitro after phagocytosis of staphylococci by blood monocytes. Antibody against the pyrogen was obtained from rabbits immunized with leukocytic pyrogen and the antiserum was purified by solid-phase immunoadsorbants. Purified antibody to the pyrogen was attached to activated Sepharose 4B and used in conjunction with gel filtration to purify the pyrogen. The pyrogen was labeled with 125I and further purified by gel filtration and ion-exchange chromatography. The final preparation of 125I-labeled pyrogen demonstrated a homogeneous band during isoelectric focusing and other separation procedures. With antibody to pyrogen attached to Sepharose, less than 0.1 of a rabbit pyrogenic dose of human leukocytic pyrogen inhibited the binding of 125I-labeled pyrogen to this immunoadsorbant, and this inhibition was not affected by the presence of human serum. Thus, a radioimmunoassay for human leukocytic pyrogen has been developed that may be used to detect circulating pyrogen during fever in humans."}
{"id": "PMID:22080", "title": "Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen.", "content": "A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the formation of compound C from the mixed-valence state of the oxidase leads to increased absorption at 740-750 nm. The formation of compound B at -84 degrees from the fully reduced state of the oxidase causes increased absorption at 790-800 nm. Further oxidation of cytochrome oxidase results in increased infrared absorption at 820-830 nm at -60 degrees. The position of the infrared absorption band in compound C thus depends at least upon the oxidation-reduction state of heme a and its associated copper atom. Compound C contains two types of oxidized (cupric) copper; that associated with heme a is initially oxidized, and that associated with heme a3 is oxidized as a second step in the reaction with oxygen. Compound C exhibits a unique intense absorption band at 606-609 nm that is tentatively assigned to a charge transfer interaction between heme a3 in the reduced state and its associated copper in the oxidized state, with heme a and its associated copper in the oxidized state.", "contents": "Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen. A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the formation of compound C from the mixed-valence state of the oxidase leads to increased absorption at 740-750 nm. The formation of compound B at -84 degrees from the fully reduced state of the oxidase causes increased absorption at 790-800 nm. Further oxidation of cytochrome oxidase results in increased infrared absorption at 820-830 nm at -60 degrees. The position of the infrared absorption band in compound C thus depends at least upon the oxidation-reduction state of heme a and its associated copper atom. Compound C contains two types of oxidized (cupric) copper; that associated with heme a is initially oxidized, and that associated with heme a3 is oxidized as a second step in the reaction with oxygen. Compound C exhibits a unique intense absorption band at 606-609 nm that is tentatively assigned to a charge transfer interaction between heme a3 in the reduced state and its associated copper in the oxidized state, with heme a and its associated copper in the oxidized state."}
{"id": "PMID:22084", "title": "Regulation of release from isolated adrenergic secretory vesicles by ATP-mediated changes in transmembrane potential and anion permeability.", "content": "Isolated chromaffin granules release their contents when exposed to calcium, magnesium, ATP, and high levels of chloride ions. The mechanism of release is not well-understood, but changes in anion permeability may be involved. We found that another anion, thiocyanate (SCN-), also activated release in a fashion similar to chloride, while isethionate (HO-CH2-CH2SO3-) an impermeant anion, was inactive. Mg++-ATP was found to activate the uptake of 36Cl and 14C-SCN, leading us to conclude that activation of anion uptake might be involved in the release process. The 36Cl and the 14C-SCN compartments were then compared by studying displacement of the trace anions by excess cold mass. Chloride and SCN displaced large amounts of both 36Cl and 14C-SCN, while isethionate displaced little of either tracer anion. We suggest, on the basis of these data, that ATP-mediated anion uptake may be the basis for the release mechanism. Release may occur as a consequence of anion and subsequent water uptake into granules, resulting in osmotic imbalance and osmotic shock. This may also be of physiologic importance, and we propose a cellular model for secretion based on  the biochemical properties of the isolated chromaffin granule.", "contents": "Regulation of release from isolated adrenergic secretory vesicles by ATP-mediated changes in transmembrane potential and anion permeability. Isolated chromaffin granules release their contents when exposed to calcium, magnesium, ATP, and high levels of chloride ions. The mechanism of release is not well-understood, but changes in anion permeability may be involved. We found that another anion, thiocyanate (SCN-), also activated release in a fashion similar to chloride, while isethionate (HO-CH2-CH2SO3-) an impermeant anion, was inactive. Mg++-ATP was found to activate the uptake of 36Cl and 14C-SCN, leading us to conclude that activation of anion uptake might be involved in the release process. The 36Cl and the 14C-SCN compartments were then compared by studying displacement of the trace anions by excess cold mass. Chloride and SCN displaced large amounts of both 36Cl and 14C-SCN, while isethionate displaced little of either tracer anion. We suggest, on the basis of these data, that ATP-mediated anion uptake may be the basis for the release mechanism. Release may occur as a consequence of anion and subsequent water uptake into granules, resulting in osmotic imbalance and osmotic shock. This may also be of physiologic importance, and we propose a cellular model for secretion based on  the biochemical properties of the isolated chromaffin granule."}
{"id": "PMID:22085", "title": "Regulation of the growth and development of sympathetic neurons in vivo.", "content": "The superior cervical ganglion (SCG) in the neonatal mouse and rat has been employed as a model system to study the regulation of ontogeny of presynaptic cholinergic nerves and postsynaptic adrenergic neurons. During postnatal development presynaptic choline acetyltransferase (ChAc) activity increases 30- to 40-fold, whereas postsynaptic tyrosine hydroxylase (T-OH) activity rises 6- to 8-fold. Transection of the presynaptic cholinergic nerves innervating the SCG prevents the normal development of T-OH activity and the normal accumulation of T-OH enzyme molecules in each postsynaptic neuron. The trans-synaptic regulation of T-OH development is apparently mediated by acetylcholine and postsynaptic depolarization, since pharmacologic ganglionic blockade also prevents normal maturation. Ganglion decentralization also prevents the normal maturation of adrenergic nerve terminals, and the development of end-organ innervation by SCG. Consequently, trans-synaptic factors regulate the ontogeny of adrenergic terminals as well as perikarya. Moreover, normal efferent as well as afferent connections are apparently required for sympathetic development, since removal of salivary glands and orbital contents, target organs of the SCG, in neonates also prevents T-OH development in the ganglia. The postsynaptic neuron contributes to the development of presynaptic cholinergic fibers in SCG. Selective destruction of adrenergic neurons in neonatal mice with either 6-hydroxydopamine or antiserum to nerve growth factor prevents the normal maturation of ChAc activity in presynaptic terminals of SCG. Thus, presynaptic and postsynaptic cells appear to exert reciprocal regulatory influences during ontogeny.", "contents": "Regulation of the growth and development of sympathetic neurons in vivo. The superior cervical ganglion (SCG) in the neonatal mouse and rat has been employed as a model system to study the regulation of ontogeny of presynaptic cholinergic nerves and postsynaptic adrenergic neurons. During postnatal development presynaptic choline acetyltransferase (ChAc) activity increases 30- to 40-fold, whereas postsynaptic tyrosine hydroxylase (T-OH) activity rises 6- to 8-fold. Transection of the presynaptic cholinergic nerves innervating the SCG prevents the normal development of T-OH activity and the normal accumulation of T-OH enzyme molecules in each postsynaptic neuron. The trans-synaptic regulation of T-OH development is apparently mediated by acetylcholine and postsynaptic depolarization, since pharmacologic ganglionic blockade also prevents normal maturation. Ganglion decentralization also prevents the normal maturation of adrenergic nerve terminals, and the development of end-organ innervation by SCG. Consequently, trans-synaptic factors regulate the ontogeny of adrenergic terminals as well as perikarya. Moreover, normal efferent as well as afferent connections are apparently required for sympathetic development, since removal of salivary glands and orbital contents, target organs of the SCG, in neonates also prevents T-OH development in the ganglia. The postsynaptic neuron contributes to the development of presynaptic cholinergic fibers in SCG. Selective destruction of adrenergic neurons in neonatal mice with either 6-hydroxydopamine or antiserum to nerve growth factor prevents the normal maturation of ChAc activity in presynaptic terminals of SCG. Thus, presynaptic and postsynaptic cells appear to exert reciprocal regulatory influences during ontogeny."}
{"id": "PMID:22086", "title": "Intramembrane particle aggregation in erythrocyte membranes and band 3-lipid recombinants.", "content": "The low pH-induced aggregation of intramembrane particles in human erythrocyte membranes was studied in native membranes and in a reconstituted model system. A significant difference in such aggregation was found when samples of freshly prepared ghosts were compared to ghosts receiving pretreatments that removed most of spectrin-actin from underneath the membrane. All conditions effective in aggregating particles are equally effective in precipitating extracted mixtures of spectrin and actin. In Band 3-lipid recombinants, the pH-induced aggregation of particles was duplicated only in samples containing spectrin-actin that equilibrated with these recombinants in sucrose gradients. Therefore, it was proposed that spectrin-actin components, through their associations with the underlying intramembrane particles, could impede particle lateral mobility and also determine particle redistribution in erythrocyte membrane.", "contents": "Intramembrane particle aggregation in erythrocyte membranes and band 3-lipid recombinants. The low pH-induced aggregation of intramembrane particles in human erythrocyte membranes was studied in native membranes and in a reconstituted model system. A significant difference in such aggregation was found when samples of freshly prepared ghosts were compared to ghosts receiving pretreatments that removed most of spectrin-actin from underneath the membrane. All conditions effective in aggregating particles are equally effective in precipitating extracted mixtures of spectrin and actin. In Band 3-lipid recombinants, the pH-induced aggregation of particles was duplicated only in samples containing spectrin-actin that equilibrated with these recombinants in sucrose gradients. Therefore, it was proposed that spectrin-actin components, through their associations with the underlying intramembrane particles, could impede particle lateral mobility and also determine particle redistribution in erythrocyte membrane."}
{"id": "PMID:22087", "title": "The contractile basis of amoeboid movement III. Structure and dynamics of motile extracts and membrane fragments from Dictyostelium discoideum and Amoeba proteus.", "content": "Motile extracts from D, discoideum and A. proteus have been characterized in order to compare the structural dynamics and chemical regulation of movement in 2 different types of amoeboid cells. The structural dynamics of both extracts involve the formation of a nonmotile cytoskeleton followed by the contraction of actin and myosin to generate both direct contractile force and cytoplasmic streaming. The contractions are regulated by calcium ions and a threshold of ca. 1.0 X 10(-6) M calcium induces a transformation of actin to the free F-actin state which is capable of interacting with myosin. Furthermore, 3 low molecular weight proteins are concentrated along with actin and myosin during contraction and might play a regulatory role in movement. Several common characteristics of amoeba cytoplasm have been exhibited by these two types of amoeboid cells. The major contractile and \"associated\" proteins are similar, actin and associated proteins are structurally dynamic, and movement is regulated by calcium. The different modes of movement observed in different types of amoeboid cells could result from the site, rate, and extent of actin transformation followed in some regions by contractions.", "contents": "The contractile basis of amoeboid movement III. Structure and dynamics of motile extracts and membrane fragments from Dictyostelium discoideum and Amoeba proteus. Motile extracts from D, discoideum and A. proteus have been characterized in order to compare the structural dynamics and chemical regulation of movement in 2 different types of amoeboid cells. The structural dynamics of both extracts involve the formation of a nonmotile cytoskeleton followed by the contraction of actin and myosin to generate both direct contractile force and cytoplasmic streaming. The contractions are regulated by calcium ions and a threshold of ca. 1.0 X 10(-6) M calcium induces a transformation of actin to the free F-actin state which is capable of interacting with myosin. Furthermore, 3 low molecular weight proteins are concentrated along with actin and myosin during contraction and might play a regulatory role in movement. Several common characteristics of amoeba cytoplasm have been exhibited by these two types of amoeboid cells. The major contractile and \"associated\" proteins are similar, actin and associated proteins are structurally dynamic, and movement is regulated by calcium. The different modes of movement observed in different types of amoeboid cells could result from the site, rate, and extent of actin transformation followed in some regions by contractions."}
{"id": "PMID:22091", "title": "Factors affecting the urinary excretion of endogenously formed dimethyltryptamine in normal human subjects.", "content": "The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-h specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 h(-1) and 856 ng 24 h(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to increase the H ion concentration of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion.", "contents": "Factors affecting the urinary excretion of endogenously formed dimethyltryptamine in normal human subjects. The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-h specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 h(-1) and 856 ng 24 h(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to increase the H ion concentration of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion."}
{"id": "PMID:22105", "title": "Properties of four temperate bacteriophages active on Clostridium perfringens type A.", "content": "Four temperature bacteriophages (designated as PF1, PF2, PF3 and PF4) were isolated from lysogenic strains of Clostridium perfringens type A. On the basis of plaque morphology, pH stability, DNase and RNase resistance, buoyant density, one-step growth parameters and electron microscope phage dimensions, it seems that these phages are different and unrelated. Calcium was required for better phage replication. Bacterial strain S107 appears to be the only UV-inducible strain as compared with the other three lysogenic strains. PF2 has a unique pattern of pH stability showing two optima values: one at pH 5 and the second at pH 8-9. Generally, all four phages have a better resistance in acid than in alkaline pH values. The CsC1 equilibrium centrifugation patterns reveal low figures for phage PF1, PF2 and PF3 and show off the fact that PF4 lysates contain two viral particules different with respect to their densities, a property which other determinations failed to demonstrate. Each phage, except PF4, is well characterized by the parameters of the one-step growth cycle.", "contents": "Properties of four temperate bacteriophages active on Clostridium perfringens type A. Four temperature bacteriophages (designated as PF1, PF2, PF3 and PF4) were isolated from lysogenic strains of Clostridium perfringens type A. On the basis of plaque morphology, pH stability, DNase and RNase resistance, buoyant density, one-step growth parameters and electron microscope phage dimensions, it seems that these phages are different and unrelated. Calcium was required for better phage replication. Bacterial strain S107 appears to be the only UV-inducible strain as compared with the other three lysogenic strains. PF2 has a unique pattern of pH stability showing two optima values: one at pH 5 and the second at pH 8-9. Generally, all four phages have a better resistance in acid than in alkaline pH values. The CsC1 equilibrium centrifugation patterns reveal low figures for phage PF1, PF2 and PF3 and show off the fact that PF4 lysates contain two viral particules different with respect to their densities, a property which other determinations failed to demonstrate. Each phage, except PF4, is well characterized by the parameters of the one-step growth cycle."}
{"id": "PMID:22110", "title": "Hemolytic activity of a lipid material obtained from peroxidized microsomes.", "content": "Lipid peroxidation was induced in rat liver microsomes by the addition of NADPH. When mixed with red cells in the presence of EDTA, these peroxidized microsomes caused hemolysis. All of the hemolytic activity of peroxidized microsomes could be extracted with lipid solvents and recovered as an aqueous lipid emulsion.", "contents": "Hemolytic activity of a lipid material obtained from peroxidized microsomes. Lipid peroxidation was induced in rat liver microsomes by the addition of NADPH. When mixed with red cells in the presence of EDTA, these peroxidized microsomes caused hemolysis. All of the hemolytic activity of peroxidized microsomes could be extracted with lipid solvents and recovered as an aqueous lipid emulsion."}
{"id": "PMID:22111", "title": "Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis.", "content": "Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins.", "contents": "Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis. Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins."}
{"id": "PMID:22112", "title": "III. Covalent coupling of rat liver phenylalanine hydroxylase.", "content": "Optimal conditions have been determined for the coupling of rat liver phenylalanine hydroxylase (PheH) to  activated CH-Sepharose-4B. When 12 mg of ligand was reacted with 100 mg of matrix, 20% of the initial enzyme activity was covalently bound along with 55% of the protein. The coupled enzyme showed greater thermal stability from 50 degrees to 60 degrees after heating for 15 min, a lower optimum pH, 5.8, slightly less inhibition by Ag+, Cu+2, and Hg+2, and greater resistance to hydrolysis by alpha-chymotrypsin and protease. The uncoupled enzyme, however, exhibited greater storage stability than the covalently linked enzyme at 25 degrees after 24 hrs and at 0 degrees after 21 days. Alteration of the microenvironment by the introduction of sulfhydryl groups and positive and negative charged carriers during coupling of the enzyme either had no effect or markedly reduced hydroxylase activity.", "contents": "III. Covalent coupling of rat liver phenylalanine hydroxylase. Optimal conditions have been determined for the coupling of rat liver phenylalanine hydroxylase (PheH) to  activated CH-Sepharose-4B. When 12 mg of ligand was reacted with 100 mg of matrix, 20% of the initial enzyme activity was covalently bound along with 55% of the protein. The coupled enzyme showed greater thermal stability from 50 degrees to 60 degrees after heating for 15 min, a lower optimum pH, 5.8, slightly less inhibition by Ag+, Cu+2, and Hg+2, and greater resistance to hydrolysis by alpha-chymotrypsin and protease. The uncoupled enzyme, however, exhibited greater storage stability than the covalently linked enzyme at 25 degrees after 24 hrs and at 0 degrees after 21 days. Alteration of the microenvironment by the introduction of sulfhydryl groups and positive and negative charged carriers during coupling of the enzyme either had no effect or markedly reduced hydroxylase activity."}
{"id": "PMID:22113", "title": "[An experimental study on the pathogenesis of the acute pulmonary insufficiency (author's transl)].", "content": "Parameters of the lungs as Compliance PaCO2, PaO2, have been measured in connection with experimental, pathophysiological insults like hematoma, bone marrow intravasation and hemorrhage, in rabbits. Concerning the compliance quotient, a statistically proved decrease was found within the groups, which have had a hematoma. Moreover, the histological picture of the lungs from rabbits with a hematom showed perivascular and intersitial edema and considerable atelectases. Serum of animals, which have had a hematom for at least 24 h has been fractionated by gel chromatography; low molecular weight substances of the fractionated serum were injected into healthy recipients. Thereafter, measurement of the centralvenous pressure suggests the appearance of substances, pharmacodynamic similar to 5-Hydroxytryptamin, in blood of rabbits with hematom.", "contents": "[An experimental study on the pathogenesis of the acute pulmonary insufficiency (author's transl)]. Parameters of the lungs as Compliance PaCO2, PaO2, have been measured in connection with experimental, pathophysiological insults like hematoma, bone marrow intravasation and hemorrhage, in rabbits. Concerning the compliance quotient, a statistically proved decrease was found within the groups, which have had a hematoma. Moreover, the histological picture of the lungs from rabbits with a hematom showed perivascular and intersitial edema and considerable atelectases. Serum of animals, which have had a hematom for at least 24 h has been fractionated by gel chromatography; low molecular weight substances of the fractionated serum were injected into healthy recipients. Thereafter, measurement of the centralvenous pressure suggests the appearance of substances, pharmacodynamic similar to 5-Hydroxytryptamin, in blood of rabbits with hematom."}
{"id": "PMID:22114", "title": "[Calculation of the pH profile in the intercapillary regions of tumour tissues before and after long-term glucose infusion into the blood stream (author's transl)].", "content": "The pH profile in the intercapillary region of tumor tissue is calculated for normal (Case I) and enhanced glucose concentration in blood (Case II) which was increased by a factor of 4 for an extended period of time. The statement used, which takes into account the reduced lactic acid formation in the unsaturated region of cancer cell glycolysis, and the resulting solution of the lactic acid diffusion field equation are given. For Case II (conditions of cancer multistep therapy) and a capillary radius of 4 micrometer this yields the following pH values: Wall at venous end of the capillary 6.7 (or 6.5); at R greater than 12 micrometer, i.e. still in the vicinity of the capillary less  than 6.3: at R approximately 60 micrometer a minimum of 5.9. This rather good pH homogeneity is the prerequisite that all lytic actions and activation mechanism induced by a temporary extreme hyperacidification of the tumor tissue can take place in the major portion of the intercapillary region with a strength of adequate uniformity. Conclusions were drawn from these results with respect to the further planning of cancer therapy. This refers to the utilization of processes serving to increase primary damage to tumor tissue through body defense mechanisms, inhibition of cell proliferation as well as the applicability of new anticancer drugs (CMT Selectines) that are rendered active only in strongly hyperacidified foci of cancer. Moreover, this includes the possible use for increasing the secondary damage to tumor tissue by way of the lysosomal cytolysis, by drastic decrease of microcirculation and the damage of the capillaries in tumor tissue.", "contents": "[Calculation of the pH profile in the intercapillary regions of tumour tissues before and after long-term glucose infusion into the blood stream (author's transl)]. The pH profile in the intercapillary region of tumor tissue is calculated for normal (Case I) and enhanced glucose concentration in blood (Case II) which was increased by a factor of 4 for an extended period of time. The statement used, which takes into account the reduced lactic acid formation in the unsaturated region of cancer cell glycolysis, and the resulting solution of the lactic acid diffusion field equation are given. For Case II (conditions of cancer multistep therapy) and a capillary radius of 4 micrometer this yields the following pH values: Wall at venous end of the capillary 6.7 (or 6.5); at R greater than 12 micrometer, i.e. still in the vicinity of the capillary less  than 6.3: at R approximately 60 micrometer a minimum of 5.9. This rather good pH homogeneity is the prerequisite that all lytic actions and activation mechanism induced by a temporary extreme hyperacidification of the tumor tissue can take place in the major portion of the intercapillary region with a strength of adequate uniformity. Conclusions were drawn from these results with respect to the further planning of cancer therapy. This refers to the utilization of processes serving to increase primary damage to tumor tissue through body defense mechanisms, inhibition of cell proliferation as well as the applicability of new anticancer drugs (CMT Selectines) that are rendered active only in strongly hyperacidified foci of cancer. Moreover, this includes the possible use for increasing the secondary damage to tumor tissue by way of the lysosomal cytolysis, by drastic decrease of microcirculation and the damage of the capillaries in tumor tissue."}
{"id": "PMID:22115", "title": "Phenylalanine inhibited p-nitrophenyl phosphatase activity in the serum as an indication of intestinal cellular disruption in the horse.", "content": "Examination of tissues obtained from thoroughbred horses showed that the 'intestinal' phosphatase activity could be differentiated from other phosphatases by analysis at a pH of 9-5 and inhibition with 15 mM L-phenylalanine. A simple method for the measurement of 'intestinal' phosphatase in heparinised plasma or serum is described. Application of the technique to serum or plasma from normal and diseased horses indicates that the increase in the activity of 'intestinal' phosphatase is associated with cases showing clinical, biochemical and haematological evidence of intestinal damage.", "contents": "Phenylalanine inhibited p-nitrophenyl phosphatase activity in the serum as an indication of intestinal cellular disruption in the horse. Examination of tissues obtained from thoroughbred horses showed that the 'intestinal' phosphatase activity could be differentiated from other phosphatases by analysis at a pH of 9-5 and inhibition with 15 mM L-phenylalanine. A simple method for the measurement of 'intestinal' phosphatase in heparinised plasma or serum is described. Application of the technique to serum or plasma from normal and diseased horses indicates that the increase in the activity of 'intestinal' phosphatase is associated with cases showing clinical, biochemical and haematological evidence of intestinal damage."}
{"id": "PMID:22116", "title": "Effects of intraruminal administration of zinc on gastric acid secretion in sheep.", "content": "Intraruminal administration of zinc sulphate at 100 and 200 mg Zn/kg bodyweight resulted in central and peripheral effects in sheep. Feed intake was reduced, pH of the duodenal contents elevated and the secretion of acid from isolated pouches of the abomasum doubled. Suggested explanations include a local inhibitory effect of zinc on abomasal acid secretion elevating duodenal pH and a resultant increased release of gastrin stimulating secretion from the pouches.", "contents": "Effects of intraruminal administration of zinc on gastric acid secretion in sheep. Intraruminal administration of zinc sulphate at 100 and 200 mg Zn/kg bodyweight resulted in central and peripheral effects in sheep. Feed intake was reduced, pH of the duodenal contents elevated and the secretion of acid from isolated pouches of the abomasum doubled. Suggested explanations include a local inhibitory effect of zinc on abomasal acid secretion elevating duodenal pH and a resultant increased release of gastrin stimulating secretion from the pouches."}
{"id": "PMID:22117", "title": "Blood acid-base state at a variable temperature. A graphical representation.", "content": "When blood temperature is changed in closed system ('anaerobic') conditions, plasma pH and PCO2 vary but no titration by external CO2, acid or alkaline equivalents takes place. It is therefore assumed that the overall acid-base state undergoes no fundamental change. This is further justified by the constancy of osmotic relationships between plasma and red cells, and to a lesser extent of relative alkalinity and protein alpha imidazole (Reeves, 1972, 1976a, b). These considerations serve as a basis for a correction procedure of pH and PCO2 of blood in open systems in vivo to a standard temperature T* (25 degrees C, eventually 37 degrees C). The temperature-corrected values pH* and P*CO2, and the derived [HCO3]* can be represented on a temperature-independent bicarbonate-pH diagram. This permits an easier interpretation of blood acid-base changes occurring together with body temperature variations, such as in ectotherms, hibernators or in artificial hypothermia. Extension to intracellular pH is considered.", "contents": "Blood acid-base state at a variable temperature. A graphical representation. When blood temperature is changed in closed system ('anaerobic') conditions, plasma pH and PCO2 vary but no titration by external CO2, acid or alkaline equivalents takes place. It is therefore assumed that the overall acid-base state undergoes no fundamental change. This is further justified by the constancy of osmotic relationships between plasma and red cells, and to a lesser extent of relative alkalinity and protein alpha imidazole (Reeves, 1972, 1976a, b). These considerations serve as a basis for a correction procedure of pH and PCO2 of blood in open systems in vivo to a standard temperature T* (25 degrees C, eventually 37 degrees C). The temperature-corrected values pH* and P*CO2, and the derived [HCO3]* can be represented on a temperature-independent bicarbonate-pH diagram. This permits an easier interpretation of blood acid-base changes occurring together with body temperature variations, such as in ectotherms, hibernators or in artificial hypothermia. Extension to intracellular pH is considered."}
{"id": "PMID:22123", "title": "Hemodynamic effects of two cardioselective beta-adrenoceptive antagonists, metoprolol and H 87/07, in coronary insufficiency.", "content": "Nineteen patients with ischemic heart disease were randomized into two groups and received either metoprolol or H 87/07. Heart catheterization was performed, and the groups were studied at rest and during exercise--before and after intravenous drug administration. During work metoprolol gave a statistically significant reduction in left ventricular work (expressed as pressure-rate product) of about 20%, mainly depending on a reduction in heart rate. Cardiac output decreased by 21%. Stroke volume was almost unchanged. The abnormal increase in left ventricular filling pressure during work was slightly, but not significantly, reduced by the drug. For H 87/07 no significant changes were found in the corresponding variables. This seems, however, to depend on an inadequate dosage, since not even the heart rate during work was significantly reduced. In conclusion, in the doses used metoprolol has been shown to be a potent beta-adrenoceptive antagonist in contrast to H 87/07.", "contents": "Hemodynamic effects of two cardioselective beta-adrenoceptive antagonists, metoprolol and H 87/07, in coronary insufficiency. Nineteen patients with ischemic heart disease were randomized into two groups and received either metoprolol or H 87/07. Heart catheterization was performed, and the groups were studied at rest and during exercise--before and after intravenous drug administration. During work metoprolol gave a statistically significant reduction in left ventricular work (expressed as pressure-rate product) of about 20%, mainly depending on a reduction in heart rate. Cardiac output decreased by 21%. Stroke volume was almost unchanged. The abnormal increase in left ventricular filling pressure during work was slightly, but not significantly, reduced by the drug. For H 87/07 no significant changes were found in the corresponding variables. This seems, however, to depend on an inadequate dosage, since not even the heart rate during work was significantly reduced. In conclusion, in the doses used metoprolol has been shown to be a potent beta-adrenoceptive antagonist in contrast to H 87/07."}
{"id": "PMID:22124", "title": "Diagnosis of symptomatic gastroesophageal reflux by prolonged monitoring of lower esophageal pH.", "content": "Lower esophageal pH was continuously monitored for 15 hours in 10 asymptomatic subjects and 27 patients with symptoms of gastroesophageal reflux, and the pH measurements in symptomatic patients were compared with the results of other esophageal investigations. Symptomatic patients had significantly longer periods of reflux in the pH test than asymptomatic subjects (P less than 0.01), but there was no significant correlation between the pH measurements and the results of esophageal manometry, acid-perfusion, and acid-clearing tests. Ten patients had evidence of esophagitis at esophagoscopy, but there was no correlation between pH measurements and the findings at esophagoscopy. Two patients with esophagitis had no evidence of reflux in the pH monitoring test. The results indicate that the pH-monitoring test has a useful role in the diagnosis of gastroesophageal reflux in patients who do not have endoscopic signs of esophagitis. However, negative pH tests do not exclude the diagnosis of symptomatic reflux, and it appears that the test has no value in assessing the severity of esophageal inflammation.", "contents": "Diagnosis of symptomatic gastroesophageal reflux by prolonged monitoring of lower esophageal pH. Lower esophageal pH was continuously monitored for 15 hours in 10 asymptomatic subjects and 27 patients with symptoms of gastroesophageal reflux, and the pH measurements in symptomatic patients were compared with the results of other esophageal investigations. Symptomatic patients had significantly longer periods of reflux in the pH test than asymptomatic subjects (P less than 0.01), but there was no significant correlation between the pH measurements and the results of esophageal manometry, acid-perfusion, and acid-clearing tests. Ten patients had evidence of esophagitis at esophagoscopy, but there was no correlation between pH measurements and the findings at esophagoscopy. Two patients with esophagitis had no evidence of reflux in the pH monitoring test. The results indicate that the pH-monitoring test has a useful role in the diagnosis of gastroesophageal reflux in patients who do not have endoscopic signs of esophagitis. However, negative pH tests do not exclude the diagnosis of symptomatic reflux, and it appears that the test has no value in assessing the severity of esophageal inflammation."}
{"id": "PMID:22126", "title": "Cigarette smoke activates guanylate cyclase and increases guanosine 3',5'-monophosphate in tissues.", "content": "The gaseous phase of cigarette smoke induced a 2- to 36-fold increase in the activity of guanylate cyclase in supernatant and particulate fractions from various rat and bovine tissues over basal activity. The characteristics of this phenomenon paralleled those of the activation of guanylate cyclase by nitric oxide, which is a component of tobacco smoke.", "contents": "Cigarette smoke activates guanylate cyclase and increases guanosine 3',5'-monophosphate in tissues. The gaseous phase of cigarette smoke induced a 2- to 36-fold increase in the activity of guanylate cyclase in supernatant and particulate fractions from various rat and bovine tissues over basal activity. The characteristics of this phenomenon paralleled those of the activation of guanylate cyclase by nitric oxide, which is a component of tobacco smoke."}
{"id": "PMID:22127", "title": "Cytidine 3',5'-monophosphate (cyclic CMP) formation in mammalian tissues.", "content": "Mammalian tissues possess the capacity to synthesize cytidine 3',5'-monopHosphate (cyclic CMP) via the enzymatic conversion of cytidine 5'-triphosphate to cyclic CMP by cytidylate cyclase. Cyclic CMP formation occurs best in the presence of manganese or iron, at neutral pH, at 37 degrees C, in the absence of detergents, and with whole tissue homogenate fractions. Thus, mammalian tissues are capable of synthesizing not only cyclic AMP and cyclic GMP, but also cyclic CMP.", "contents": "Cytidine 3',5'-monophosphate (cyclic CMP) formation in mammalian tissues. Mammalian tissues possess the capacity to synthesize cytidine 3',5'-monopHosphate (cyclic CMP) via the enzymatic conversion of cytidine 5'-triphosphate to cyclic CMP by cytidylate cyclase. Cyclic CMP formation occurs best in the presence of manganese or iron, at neutral pH, at 37 degrees C, in the absence of detergents, and with whole tissue homogenate fractions. Thus, mammalian tissues are capable of synthesizing not only cyclic AMP and cyclic GMP, but also cyclic CMP."}
{"id": "PMID:22128", "title": "[Follow-up study of non-neoplastic Cushing's syndrome followed by paraneoplastic Cushing's syndrome after removal of a malignant pulmonary tumor. Role of the diffuse endocrine system and APUD (amine precursor uptake decarboxylase) cells].", "content": "A 27 year old woman had in 1965, a paraneoplastic Cushing's syndrome was cured by removal of a pulmonary tumour. The case was published in June 1968. After a normal pregnancy, a recurrence of the Cushing's syndrome in 1969 led in 1970 to bilateral total adrenalectomy in two stages. Pathology showed hyperplastic adrenal glands. After 11 years follow up, we have not noted any relapse of the tumour nor of the Cushing's syndrome. The pathological appearance of the lung carcinoma removed in 1965 (endocrinoid or neuroid structures) suggests that this was an \"apudoma\" and that the recurrence of the Cushing's syndrome was perhaps an \"apudomatosis\" involving the pituitary ACTH cells.", "contents": "[Follow-up study of non-neoplastic Cushing's syndrome followed by paraneoplastic Cushing's syndrome after removal of a malignant pulmonary tumor. Role of the diffuse endocrine system and APUD (amine precursor uptake decarboxylase) cells]. A 27 year old woman had in 1965, a paraneoplastic Cushing's syndrome was cured by removal of a pulmonary tumour. The case was published in June 1968. After a normal pregnancy, a recurrence of the Cushing's syndrome in 1969 led in 1970 to bilateral total adrenalectomy in two stages. Pathology showed hyperplastic adrenal glands. After 11 years follow up, we have not noted any relapse of the tumour nor of the Cushing's syndrome. The pathological appearance of the lung carcinoma removed in 1965 (endocrinoid or neuroid structures) suggests that this was an \"apudoma\" and that the recurrence of the Cushing's syndrome was perhaps an \"apudomatosis\" involving the pituitary ACTH cells."}
{"id": "PMID:22136", "title": "Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia.", "content": "Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.", "contents": "Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia. Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies."}
{"id": "PMID:22139", "title": "[Local contractility and acidosis in the ischemic myocardium of the dog (author's transl)].", "content": "In open chest dogs up to 8 side branches of the R, circumflexus and descendens were embraced and could selectively be occluded. With a new developed method local myocardial length changes in the ischemic areas, and with H+-sensitive minielectrodes the interstitial H+-activities were measured. All changes which were observed during the 3-30 min lasting coronary artery occlusions (H+-increases to about 500 neq/1, increases of diastolic length, decreases of the contraction amplitude, ST-elevations) returned to preocclusion levels during reperfusion. LVP and dp/dt remained unchanged during ischemia and reperfusion.", "contents": "[Local contractility and acidosis in the ischemic myocardium of the dog (author's transl)]. In open chest dogs up to 8 side branches of the R, circumflexus and descendens were embraced and could selectively be occluded. With a new developed method local myocardial length changes in the ischemic areas, and with H+-sensitive minielectrodes the interstitial H+-activities were measured. All changes which were observed during the 3-30 min lasting coronary artery occlusions (H+-increases to about 500 neq/1, increases of diastolic length, decreases of the contraction amplitude, ST-elevations) returned to preocclusion levels during reperfusion. LVP and dp/dt remained unchanged during ischemia and reperfusion."}
{"id": "PMID:22143", "title": "Teratological study of etoperidone in the rat and rabbit.", "content": "Etoperidone was administered to pregnant rats and rabbits during the period of organogenesis. The oral doses were 100 and 300 mg/kg in the rat and 5, 25 and 50 mg/kg in the rabbit. In the rat the dose of 300 mg/kg produced toxic effects on the mother, consisting mainly of behavioural changes and death in some cases; a slight increase in embryofetal mortality was also observed. The dose of 100 mg/kg still produced behavioural changes in the mother, but had no effect on the product of conception. Chlorcyclizine, on the other hand, used as a reference drug in the rat produced fetal malformations at a dose devoid of any toxic activity on the maternal organism. The doses studied in the rabbit were shown to be pharmacologically active in the mothers, producing sedation. No effect, however, was observed on embryofetal development.", "contents": "Teratological study of etoperidone in the rat and rabbit. Etoperidone was administered to pregnant rats and rabbits during the period of organogenesis. The oral doses were 100 and 300 mg/kg in the rat and 5, 25 and 50 mg/kg in the rabbit. In the rat the dose of 300 mg/kg produced toxic effects on the mother, consisting mainly of behavioural changes and death in some cases; a slight increase in embryofetal mortality was also observed. The dose of 100 mg/kg still produced behavioural changes in the mother, but had no effect on the product of conception. Chlorcyclizine, on the other hand, used as a reference drug in the rat produced fetal malformations at a dose devoid of any toxic activity on the maternal organism. The doses studied in the rabbit were shown to be pharmacologically active in the mothers, producing sedation. No effect, however, was observed on embryofetal development."}
{"id": "PMID:22146", "title": "In vitro biosynthesis of radioactive estradiol-17 beta, 17-glucosiduronate by rhesus monkey liver.", "content": "A method for the preparation of radioactive estradiol-17 beta, 17-glucosiduronate by incubating 3H-estradiol with rhesus monkey liver microsomal preparation in the presence of uridine diphosphoglucuronic acid is described. Small but significant amounts of the conjugate were also obtained from the 150,00 pellet and cytosol fractions. The addition of NADPH to the incubation media increased the yield of radioactive-estradiol-17 beta, 17-glucosiduronate perhaps by preserving the integrity of the C-17-hydroxyl group. As expected, the effect of the reduced nucleotide was more pronounced in the fractions other than the microsome. The biosynthesized conjugate was isolated and purified by multiple column chromatography and the structure was confirmed by derivative formation, enzyme hydrolysis and crystallization of the aglycone.", "contents": "In vitro biosynthesis of radioactive estradiol-17 beta, 17-glucosiduronate by rhesus monkey liver. A method for the preparation of radioactive estradiol-17 beta, 17-glucosiduronate by incubating 3H-estradiol with rhesus monkey liver microsomal preparation in the presence of uridine diphosphoglucuronic acid is described. Small but significant amounts of the conjugate were also obtained from the 150,00 pellet and cytosol fractions. The addition of NADPH to the incubation media increased the yield of radioactive-estradiol-17 beta, 17-glucosiduronate perhaps by preserving the integrity of the C-17-hydroxyl group. As expected, the effect of the reduced nucleotide was more pronounced in the fractions other than the microsome. The biosynthesized conjugate was isolated and purified by multiple column chromatography and the structure was confirmed by derivative formation, enzyme hydrolysis and crystallization of the aglycone."}
{"id": "PMID:22148", "title": "[Content of nicotinamide coenzymes in rat liver under conditions of nicotinamide administration].", "content": "The content of NAD+, NADH, NADP+, NADPH in the liver of normal, fasting rats, those on the low-carbohydrate diet and suffering from alloxan diabetes was studied as affected by nictotinamide. Changes in the NAD+ content, sum of nicotinamide coenzymes, the [NAD+] + [NADP+]/[NADH] +/- [NADPH] and [NAD+] + [NADH] (sum of nicotinamide coenzymes) ratios are mainly due to nicotinamide administration. Changes in the content of reduced forms of both nucleotides depend equally on nicotinamide administration and the physiological state of animals. Response of the rat organism to nicotinamide administration consists in a sharp intensification of NAD+ synthesis and in a less pronounced intensification of NADH, NADP+ and NADPH synthesis.", "contents": "[Content of nicotinamide coenzymes in rat liver under conditions of nicotinamide administration]. The content of NAD+, NADH, NADP+, NADPH in the liver of normal, fasting rats, those on the low-carbohydrate diet and suffering from alloxan diabetes was studied as affected by nictotinamide. Changes in the NAD+ content, sum of nicotinamide coenzymes, the [NAD+] + [NADP+]/[NADH] +/- [NADPH] and [NAD+] + [NADH] (sum of nicotinamide coenzymes) ratios are mainly due to nicotinamide administration. Changes in the content of reduced forms of both nucleotides depend equally on nicotinamide administration and the physiological state of animals. Response of the rat organism to nicotinamide administration consists in a sharp intensification of NAD+ synthesis and in a less pronounced intensification of NADH, NADP+ and NADPH synthesis."}
{"id": "PMID:22149", "title": "[Equilibrium system consisting of soluble forms of fibrin and the specific anticoagulant D fragment of the firbinogen molecule].", "content": "According to the authors' observations, mixtures of fibrin monomer and fibrinogen-derived D fragment are gradually transformed into an equilibrium system when fibrin exists partly in a solid clot form and partly as a soluble material made unclottable by the influence of fragment D. The amount of such a soluble fibrin proved to be a linear function of the D fragment concentration. Three fibrin monomer preparations obtained in different ways were used. All of them showed similar properties as to the modifications with D fragment. The solubilzing activity of D fragment in the equilibrium system could sharply be raised by increasing ionic strength or pH. It is known that these medium changes produce the same stimulation effect on D fragment, being examined as an inhibitor of fibrin monomer polymerization. But the concentration dependences of the two activities of D fragment differ in principle.", "contents": "[Equilibrium system consisting of soluble forms of fibrin and the specific anticoagulant D fragment of the firbinogen molecule]. According to the authors' observations, mixtures of fibrin monomer and fibrinogen-derived D fragment are gradually transformed into an equilibrium system when fibrin exists partly in a solid clot form and partly as a soluble material made unclottable by the influence of fragment D. The amount of such a soluble fibrin proved to be a linear function of the D fragment concentration. Three fibrin monomer preparations obtained in different ways were used. All of them showed similar properties as to the modifications with D fragment. The solubilzing activity of D fragment in the equilibrium system could sharply be raised by increasing ionic strength or pH. It is known that these medium changes produce the same stimulation effect on D fragment, being examined as an inhibitor of fibrin monomer polymerization. But the concentration dependences of the two activities of D fragment differ in principle."}
{"id": "PMID:22155", "title": "The sedation and anaesthesia of birds and reptiles.", "content": "Demand for veterinary care of birds and reptiles is increasing and with it a knowledge of the current methods of restraint and sedation of these classes. Some of the safer and more practical methods are reviewed and commented on in the light of recent results from the Zoological Society of London's veterinary department.", "contents": "The sedation and anaesthesia of birds and reptiles. Demand for veterinary care of birds and reptiles is increasing and with it a knowledge of the current methods of restraint and sedation of these classes. Some of the safer and more practical methods are reviewed and commented on in the light of recent results from the Zoological Society of London's veterinary department."}
{"id": "PMID:22157", "title": "[Cholinesterase activity of sperm from rams infected with Brucella ovis].", "content": "Studied were the indices of cholinesterase activity of semen taken from 23 normal rams and 23 rams infected with Brucella ovis, the latter being positive by the complement-fixation test and showing a varying deterioration of the semen production. The results obtained were processed biometrically. Established were dependable differences. The cholinesterase activity of semen of brucellosis-affected rams proved four times higher than that of normal rams' semen: 39.45 +/- 5.49 microleter TO2 for 1 hour as against 174.15 +/- 9.97 microleter. A reverse correlation was established between the values of the cholinesterase activity, and the pH value and the percent of pathologic forms of spermatozoa.", "contents": "[Cholinesterase activity of sperm from rams infected with Brucella ovis]. Studied were the indices of cholinesterase activity of semen taken from 23 normal rams and 23 rams infected with Brucella ovis, the latter being positive by the complement-fixation test and showing a varying deterioration of the semen production. The results obtained were processed biometrically. Established were dependable differences. The cholinesterase activity of semen of brucellosis-affected rams proved four times higher than that of normal rams' semen: 39.45 +/- 5.49 microleter TO2 for 1 hour as against 174.15 +/- 9.97 microleter. A reverse correlation was established between the values of the cholinesterase activity, and the pH value and the percent of pathologic forms of spermatozoa."}
{"id": "PMID:22159", "title": "Development of hemagglutination assays I. Attachment of anti-HBs antibody to stabilized erythrocytes.", "content": "Conditions favoring the coupling of antibody to human erythrocytes stabilized by a variety of reagents were studied with the use of antibody to hepatitis B surface antigen. Functional anti-HBs bound to erythrocytes was measured by radioimmune assay using 125 I-HBsAg. The attachment of anti-HBs to aldehyde-stabilized cells is favored by low pH and low ionic strength. The extent of antibody binding is both concentration and time dependent. Development of spontaneous agglutination of the coated erythrocytes occurs with the attachment of increasing quantities of anti-HBs. Although antibody was rapidly taken up by aldehyde-stabilized erythrocytes, it was initially readily dissociable, but after longer exposure became firmly bound. Experiments pertaining to the chemical nature of the more stable antibody-erythrocyte complex gave results consistent with covalent bond formation, though rigorous proof was not developed.", "contents": "Development of hemagglutination assays I. Attachment of anti-HBs antibody to stabilized erythrocytes. Conditions favoring the coupling of antibody to human erythrocytes stabilized by a variety of reagents were studied with the use of antibody to hepatitis B surface antigen. Functional anti-HBs bound to erythrocytes was measured by radioimmune assay using 125 I-HBsAg. The attachment of anti-HBs to aldehyde-stabilized cells is favored by low pH and low ionic strength. The extent of antibody binding is both concentration and time dependent. Development of spontaneous agglutination of the coated erythrocytes occurs with the attachment of increasing quantities of anti-HBs. Although antibody was rapidly taken up by aldehyde-stabilized erythrocytes, it was initially readily dissociable, but after longer exposure became firmly bound. Experiments pertaining to the chemical nature of the more stable antibody-erythrocyte complex gave results consistent with covalent bond formation, though rigorous proof was not developed."}
{"id": "PMID:22164", "title": "Lysis of intact yeast cells and isolated cell walls by an inducible enzyme system of Arthrobacter GJM-1.", "content": "Bacterium Arthrobacter GJM-1 known in the literature as a good producer of alpha-mannanase was found to accumulate in the culture fluid lytic activities against viable yeast cells during growth on isolated cell walls or beta-glucan fractions of yeast. The accumulation of the lytic activities showed an inducible character. The lytic system produced in the medium containing baker's yeast cell walls was capable of complete solubiliaztion of cell wals in vitro. The system lysed viable cells of a number of yeast species and induced their conversion to protoplasts in an osmotically stabilized medium. The lytic system showed different pH and temperature optima when viable cells or isolated cell walls were used as substrates. The pH optimum of the lysis of isolated cell walls was identical with pH optimum of beta-glucanase activities in the crude system. The results pointed out that in the lysis of intact cells, in addition to beta-glucanases, some other factor is involved. Substantial differences in the nature of the outer and the inner surface of cell walls of Saccharomuces cerevisiae  were confirmed in this paper based on the different susceptibility to lysis of the cell walls in vivo and in vitro.", "contents": "Lysis of intact yeast cells and isolated cell walls by an inducible enzyme system of Arthrobacter GJM-1. Bacterium Arthrobacter GJM-1 known in the literature as a good producer of alpha-mannanase was found to accumulate in the culture fluid lytic activities against viable yeast cells during growth on isolated cell walls or beta-glucan fractions of yeast. The accumulation of the lytic activities showed an inducible character. The lytic system produced in the medium containing baker's yeast cell walls was capable of complete solubiliaztion of cell wals in vitro. The system lysed viable cells of a number of yeast species and induced their conversion to protoplasts in an osmotically stabilized medium. The lytic system showed different pH and temperature optima when viable cells or isolated cell walls were used as substrates. The pH optimum of the lysis of isolated cell walls was identical with pH optimum of beta-glucanase activities in the crude system. The results pointed out that in the lysis of intact cells, in addition to beta-glucanases, some other factor is involved. Substantial differences in the nature of the outer and the inner surface of cell walls of Saccharomuces cerevisiae  were confirmed in this paper based on the different susceptibility to lysis of the cell walls in vivo and in vitro."}
{"id": "PMID:22167", "title": "[On the problem of dimethylnitrosamine formation from tetracycline-derivatives by nitrosation reaction in acidic medium (author's transl)].", "content": "The hydrochlorides from tetracycline and six tetracycline derivatives -- 7-dimethylamino-6-des-methyl-6-desoxytetracycline [minocycline], 7-chlorotetracycline [chlorotetracycline], 7-chloro-anhydrotetracycline [anhydrochlorotetracycline, 7-chloro-6-desmethyltetracycline [demethylchlorotetracycline], 5-hydroxytetracycline [oxytetracycline] and 6-desoxy-5-hydroxytetracycline [doxycycline] -- were reacted with different amounts of sodium nitrite at 37 degrees C for two hours in aqueous buffer solutions at pH 2 and 4. Dimethylnitrosamine formation was confirmed by gas-liquid chromatography and by combined gas-liquid chromatography/mass-spectrometry from minocycline, doxycycline, oxytetracycline and anhydrochlorotetracycline. Dimethylnitrosamine formation from minocycline and doxycycline was blocked by ascorbic acid. The catalytic effect of sodium thiocyanate for the dimethylnitrosamine formation from minocycline and nitrite was investigated. The different reactivity of the investigated tetracycline derivatives towards nitrite in acidic solutions is discussed by stereochemical considerations in connection with the formation of hydrogen bridge linkages. This hypothesis was confirmed by dimethylnitrosamine formation from anhydrochlorotetracycline and sodium nitrite at pH 2.", "contents": "[On the problem of dimethylnitrosamine formation from tetracycline-derivatives by nitrosation reaction in acidic medium (author's transl)]. The hydrochlorides from tetracycline and six tetracycline derivatives -- 7-dimethylamino-6-des-methyl-6-desoxytetracycline [minocycline], 7-chlorotetracycline [chlorotetracycline], 7-chloro-anhydrotetracycline [anhydrochlorotetracycline, 7-chloro-6-desmethyltetracycline [demethylchlorotetracycline], 5-hydroxytetracycline [oxytetracycline] and 6-desoxy-5-hydroxytetracycline [doxycycline] -- were reacted with different amounts of sodium nitrite at 37 degrees C for two hours in aqueous buffer solutions at pH 2 and 4. Dimethylnitrosamine formation was confirmed by gas-liquid chromatography and by combined gas-liquid chromatography/mass-spectrometry from minocycline, doxycycline, oxytetracycline and anhydrochlorotetracycline. Dimethylnitrosamine formation from minocycline and doxycycline was blocked by ascorbic acid. The catalytic effect of sodium thiocyanate for the dimethylnitrosamine formation from minocycline and nitrite was investigated. The different reactivity of the investigated tetracycline derivatives towards nitrite in acidic solutions is discussed by stereochemical considerations in connection with the formation of hydrogen bridge linkages. This hypothesis was confirmed by dimethylnitrosamine formation from anhydrochlorotetracycline and sodium nitrite at pH 2."}
{"id": "PMID:22168", "title": "On the mechanism of inactivation and ATP-dependent reactivation of rat liver tyrosine aminotransferase.", "content": "The mechanism of in vitro inactivation and ATP-dependent rapid reactivation of rat liver tyrosine aminotransferase by a membrane-bound system from rat liver and kidney cortex and the nucleotide specificity of this process was investigated using partially purified tyrosine amino-transferase as a substrate. Adenosine 5'-triphosphate (ATP) could be replaced by guanosine 5'-triphosphate (GTP), Whereas inosine 5'-triphosphate (ITP) was less effective. During reactivation [gamma-32P]ATP was incorporated into the enzyme and not excorporated by incubation of the labeled enzyme with excess non-radioative ATP. Inactivation of labeled tyrosine aminotransferase by a particulate fraction led to a decrease protein-bound radioactivity concomitant with an increase of [32P]orthophosphate. This points to a phosphorylation and dephosphorylation mechanism in the regulation of tyrosine aminotransferase activity.", "contents": "On the mechanism of inactivation and ATP-dependent reactivation of rat liver tyrosine aminotransferase. The mechanism of in vitro inactivation and ATP-dependent rapid reactivation of rat liver tyrosine aminotransferase by a membrane-bound system from rat liver and kidney cortex and the nucleotide specificity of this process was investigated using partially purified tyrosine amino-transferase as a substrate. Adenosine 5'-triphosphate (ATP) could be replaced by guanosine 5'-triphosphate (GTP), Whereas inosine 5'-triphosphate (ITP) was less effective. During reactivation [gamma-32P]ATP was incorporated into the enzyme and not excorporated by incubation of the labeled enzyme with excess non-radioative ATP. Inactivation of labeled tyrosine aminotransferase by a particulate fraction led to a decrease protein-bound radioactivity concomitant with an increase of [32P]orthophosphate. This points to a phosphorylation and dephosphorylation mechanism in the regulation of tyrosine aminotransferase activity."}
{"id": "PMID:22171", "title": "[Thioacylamides and thioacylureas as inhibitors of photosystem II (author's transl)].", "content": "Thioacylureas and thioacylamides were found to inhibit photosynthetic O2-evolution (Hill-reactions) of \"broken chloroplasts\", some derivatives approaching an I50 of 10(-5) M. The inhibition site is near photosystem II. The inhibitory effects of the tested derivatives vary in theri pH-dependency between pH 5 and 8.", "contents": "[Thioacylamides and thioacylureas as inhibitors of photosystem II (author's transl)]. Thioacylureas and thioacylamides were found to inhibit photosynthetic O2-evolution (Hill-reactions) of \"broken chloroplasts\", some derivatives approaching an I50 of 10(-5) M. The inhibition site is near photosystem II. The inhibitory effects of the tested derivatives vary in theri pH-dependency between pH 5 and 8."}
{"id": "PMID:22208", "title": "[Researches to the conversion of sorbit into sorbose by Acetobacter suboxydans (author's transl)].", "content": "The production of sorbose by Acetobacter suboxydans (4) is closely related to the concentration of sorbit in the medium. An increasing concentration of sorbit gives rise to the inhibition of cell reproduction; followed by a decrease of sorbose content in the culture medium. The decrease of sorbose yield in concentrations of about 15% sorbit in medium indicates the decreasing metabolism rate of the total population of Acetobacter suboxydans (4) culture and does not refer to the ability of the individual bacterium cell to produce sorbose. Relevant research work showed, that sorbose production for each bacterium cell distinctly increased with the decrease of the number of cells in a population of Acetobacter suboxydans (4) as a consequence of the application of an increased sorbit concentration. An unrestrained reproduction of bacteria could be obtained by exluding all factors involved in the contamination of sorbit and exhibiting toxic effects. Therefore the organisms could be offered a greater concentration of sorbit for conversion into sorbose. Thus sorbose yield would be increased, respectively. The total conversion of the C-source into sorbose could not be obtained with Acetobacter ruboxydans (4).", "contents": "[Researches to the conversion of sorbit into sorbose by Acetobacter suboxydans (author's transl)]. The production of sorbose by Acetobacter suboxydans (4) is closely related to the concentration of sorbit in the medium. An increasing concentration of sorbit gives rise to the inhibition of cell reproduction; followed by a decrease of sorbose content in the culture medium. The decrease of sorbose yield in concentrations of about 15% sorbit in medium indicates the decreasing metabolism rate of the total population of Acetobacter suboxydans (4) culture and does not refer to the ability of the individual bacterium cell to produce sorbose. Relevant research work showed, that sorbose production for each bacterium cell distinctly increased with the decrease of the number of cells in a population of Acetobacter suboxydans (4) as a consequence of the application of an increased sorbit concentration. An unrestrained reproduction of bacteria could be obtained by exluding all factors involved in the contamination of sorbit and exhibiting toxic effects. Therefore the organisms could be offered a greater concentration of sorbit for conversion into sorbose. Thus sorbose yield would be increased, respectively. The total conversion of the C-source into sorbose could not be obtained with Acetobacter ruboxydans (4)."}
{"id": "PMID:22209", "title": "Studies on phosphate-solubilizing bacteria in soil and rhizosphere of different plants. I. Occurrence of bacteria, acid producers, and phosphate dissolvers.", "content": "Occurrence of bacteria (total), acid producing and phosphate dissolving micro-organisms in soil, rhizosphere, and rizoplane of Egyptian cotton, peas, or maize during their different growth phases was studied. The rhizosphere effects were generally positive and differed according to type of plant, growth phase of each special plant, and type of micro-organism under study. The high densities of bacteria, acid-producers, and phosphate-dissolvers in the rhizoplane samples suggest the conclusion that roots of the studied plants are colonized with these soil micro-organisms. The role of the micro-organism and the mechanism of the noted colonization is not fully understood yet. However, the presence of high numbers of bacteria in the rhizosphere zones of all plants is undoubtedly important, since they may convert organic and inorganic substances into available plant nutrients. The acidproducing organisms were greatly stimulated in the rhizosphere of all plants. Consequently, the production of acid, especially in alkaline soils such as in Egypt, may directly or indirectly react with insoluble inorganic compounds, converting their nutrient elements into available forms for the growing plants. But not all acid-producers are considered as phosphate-dissolvers. Therefore, the presence of high numbers of phosphate-dissolving bacteria in the rhizophere zones may explain how the growing plants can obtain their requirements in such alkaline soils.", "contents": "Studies on phosphate-solubilizing bacteria in soil and rhizosphere of different plants. I. Occurrence of bacteria, acid producers, and phosphate dissolvers. Occurrence of bacteria (total), acid producing and phosphate dissolving micro-organisms in soil, rhizosphere, and rizoplane of Egyptian cotton, peas, or maize during their different growth phases was studied. The rhizosphere effects were generally positive and differed according to type of plant, growth phase of each special plant, and type of micro-organism under study. The high densities of bacteria, acid-producers, and phosphate-dissolvers in the rhizoplane samples suggest the conclusion that roots of the studied plants are colonized with these soil micro-organisms. The role of the micro-organism and the mechanism of the noted colonization is not fully understood yet. However, the presence of high numbers of bacteria in the rhizosphere zones of all plants is undoubtedly important, since they may convert organic and inorganic substances into available plant nutrients. The acidproducing organisms were greatly stimulated in the rhizosphere of all plants. Consequently, the production of acid, especially in alkaline soils such as in Egypt, may directly or indirectly react with insoluble inorganic compounds, converting their nutrient elements into available forms for the growing plants. But not all acid-producers are considered as phosphate-dissolvers. Therefore, the presence of high numbers of phosphate-dissolving bacteria in the rhizophere zones may explain how the growing plants can obtain their requirements in such alkaline soils."}
{"id": "PMID:22210", "title": "Studies on phosphate-solubilizing bacteria in soil and rhizosphere of different plants. II. Selection of the most efficient phosphate-dissolvers and their morphological grouping.", "content": "Two hundred colonies which showed positive reaction on the plates prepared for the phosphate-dissolving bacteria from control soil rhizosphere soils and rhizoplane samples of maize, peas, or cotton were isolated at random. Fifty isolates were selected as the most efficient isolates according to their capability for increasing the amounts of available phosphorus in the media with corresponding decreases in pH values. The percentage of the most efficient isolates differed according to type of plant and location of isolation. Not only the morphological types of the phosphate-dissolving bacteria differed in soil and in rhizosphere, but they also differed in the rhizosphere soil of each special plant. Morphological differences in the isolates from rhizosphere soil and from rhizoplane samples of the same plant were also occurring. The abundance of mycelial-forming bacteria and of aerobic sporeformers in Egyptian soil is important as they are well known to resist adverse conditions, such as high temperature and dryness to which our soils are subjected most time of the year.", "contents": "Studies on phosphate-solubilizing bacteria in soil and rhizosphere of different plants. II. Selection of the most efficient phosphate-dissolvers and their morphological grouping. Two hundred colonies which showed positive reaction on the plates prepared for the phosphate-dissolving bacteria from control soil rhizosphere soils and rhizoplane samples of maize, peas, or cotton were isolated at random. Fifty isolates were selected as the most efficient isolates according to their capability for increasing the amounts of available phosphorus in the media with corresponding decreases in pH values. The percentage of the most efficient isolates differed according to type of plant and location of isolation. Not only the morphological types of the phosphate-dissolving bacteria differed in soil and in rhizosphere, but they also differed in the rhizosphere soil of each special plant. Morphological differences in the isolates from rhizosphere soil and from rhizoplane samples of the same plant were also occurring. The abundance of mycelial-forming bacteria and of aerobic sporeformers in Egyptian soil is important as they are well known to resist adverse conditions, such as high temperature and dryness to which our soils are subjected most time of the year."}
{"id": "PMID:22212", "title": "The N4-hydroxycytidine reduction system in toluenized cells of Salmonella typhimurium.", "content": "1. Enzymatic reduction of N4-hydroxycytidine to cytidine in Salmonella typhimurium is highly specific. The reaction occurs only at the nucleoside level. Free base or its 1-methyl analogue is not reduced. 2. The pH optimum shows a broad plateau with a maximum at pH 7.0. The apparent Km value, estimated in the toluene-treated cells, is 4.8 mM and Vmax 1.4 nmoles/min/mg of wet bacterial weight. The reaction is NADH-dependent, although in toluenized bacterial cells it can occure without addition of any exogenous factor.", "contents": "The N4-hydroxycytidine reduction system in toluenized cells of Salmonella typhimurium. 1. Enzymatic reduction of N4-hydroxycytidine to cytidine in Salmonella typhimurium is highly specific. The reaction occurs only at the nucleoside level. Free base or its 1-methyl analogue is not reduced. 2. The pH optimum shows a broad plateau with a maximum at pH 7.0. The apparent Km value, estimated in the toluene-treated cells, is 4.8 mM and Vmax 1.4 nmoles/min/mg of wet bacterial weight. The reaction is NADH-dependent, although in toluenized bacterial cells it can occure without addition of any exogenous factor."}
{"id": "PMID:22213", "title": "Intrauterine hypoxia -- a phenomenon peculiar to the second twin.", "content": "During a 5-year period twin births occurring at the university hospital were investigated for the presence of clinical and biochemical symptoms of intrauterine hypoxia. It appears that intrauterine hypoxia, when detectable, is limited to the second twin. Some factors which may influence the oxygenation of the second twin have been analysed, i.e., the mode of delivery, the time interval between deliveries, and the duration of gestation. No single explanation for the genesis of the hypoxia seems to be valid.", "contents": "Intrauterine hypoxia -- a phenomenon peculiar to the second twin. During a 5-year period twin births occurring at the university hospital were investigated for the presence of clinical and biochemical symptoms of intrauterine hypoxia. It appears that intrauterine hypoxia, when detectable, is limited to the second twin. Some factors which may influence the oxygenation of the second twin have been analysed, i.e., the mode of delivery, the time interval between deliveries, and the duration of gestation. No single explanation for the genesis of the hypoxia seems to be valid."}
{"id": "PMID:22214", "title": "Clinical trial with lorazepam in pre-operative anxiety.", "content": "An important part of the pre-operative preparation of a patient consists in the treatment of his anxiety. One hundred eighty-two patients (varying in age from 17 to 80 years) were sedated for surgery with lorazepam. The evening before intervention, each patient received 1 tablet of lorazepam (2.5 mg) and on the day of operation (90 minutes before induction of the anesthesia), each patient received an I.M. injection of lorazepam and atropine, the dosage being adjusted to body weight. The prior administration of lorazepam usually gives very good results with only slight risk of side-effects and without unhappy recollections of the pre- and post-operative periods. Most of the patients were very calm, being well rested, conscious and capable of conversation. In our experience the sedation of anxious patients with lorazepam would seem to be a very good and safe procedure.", "contents": "Clinical trial with lorazepam in pre-operative anxiety. An important part of the pre-operative preparation of a patient consists in the treatment of his anxiety. One hundred eighty-two patients (varying in age from 17 to 80 years) were sedated for surgery with lorazepam. The evening before intervention, each patient received 1 tablet of lorazepam (2.5 mg) and on the day of operation (90 minutes before induction of the anesthesia), each patient received an I.M. injection of lorazepam and atropine, the dosage being adjusted to body weight. The prior administration of lorazepam usually gives very good results with only slight risk of side-effects and without unhappy recollections of the pre- and post-operative periods. Most of the patients were very calm, being well rested, conscious and capable of conversation. In our experience the sedation of anxious patients with lorazepam would seem to be a very good and safe procedure."}
{"id": "PMID:22215", "title": "Enzyme histochemical study on hepatoma--the relation between enzyme activity and histological type.", "content": "The activities of gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (A-p), and leucine aminopeptidase (LAP) were examined in 18 cases of hepatomas. The activity of gamma-GTP was most remarkable in the hepatoma consisting of small to medium-sized tumor cells showing the least atypism. The enzyme activity found in the type composed of large tumor cells resembled that of normal liver and was considered to be the most mature form of the neoplasm. This enzyme was not found in the immature type composed of small typical tumor cells. A-P activity was seen in only a few cases of hepatoma; conspicuous in one case showing immature features and sporadically in one case with florid histological pattern. The activity of this enzyme could not be confirmed in the type demonstrating marked gamma-GTP activity. LAP activity was noted in the majority of cases, especially marked in the medium-sized tumor cells, but there was hardly any connection between this enzyme and histological type. In general, the cases demonstrating positive gamma-GTP activity tended to show LAP activity. Although the activity of gamma-GTP and that of A-p usually showed an inverse relation, all three enzymes demonstrated almost equal activity in the type showing a florid histological pattern.", "contents": "Enzyme histochemical study on hepatoma--the relation between enzyme activity and histological type. The activities of gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (A-p), and leucine aminopeptidase (LAP) were examined in 18 cases of hepatomas. The activity of gamma-GTP was most remarkable in the hepatoma consisting of small to medium-sized tumor cells showing the least atypism. The enzyme activity found in the type composed of large tumor cells resembled that of normal liver and was considered to be the most mature form of the neoplasm. This enzyme was not found in the immature type composed of small typical tumor cells. A-P activity was seen in only a few cases of hepatoma; conspicuous in one case showing immature features and sporadically in one case with florid histological pattern. The activity of this enzyme could not be confirmed in the type demonstrating marked gamma-GTP activity. LAP activity was noted in the majority of cases, especially marked in the medium-sized tumor cells, but there was hardly any connection between this enzyme and histological type. In general, the cases demonstrating positive gamma-GTP activity tended to show LAP activity. Although the activity of gamma-GTP and that of A-p usually showed an inverse relation, all three enzymes demonstrated almost equal activity in the type showing a florid histological pattern."}
{"id": "PMID:22217", "title": "An improved direct colorimetric method for the quantitative analysis of urinary hippuric acid as an index of toluene exposure.", "content": "An improved direct colorimetric method for determining the concentration of urinary hippuric acid as an index of toluene exposure was described. One tenth ml of urine was diluted with 0.4 ml 0.01 M phosphate buffer H 6.9 and mixed with 0.5 ml pyridine. The mixture was layered on 0.2 ml benzenesulfonyl chloride. The reaction was started by mixing for one min with a mechanical shaker. The colored solution was allowed to stand for 30 min, diluted with 5 ml ethanol, and absorbance measured at 410 nm within 30 min after the dilution. The coefficient of variation of this method was 6% and the recovery 103% when urine contains about 0.2-0.5 mg hippuric acid per ml of urine. The concentration was linear up to 2.0 mg per ml hippuric acid in a specimen.", "contents": "An improved direct colorimetric method for the quantitative analysis of urinary hippuric acid as an index of toluene exposure. An improved direct colorimetric method for determining the concentration of urinary hippuric acid as an index of toluene exposure was described. One tenth ml of urine was diluted with 0.4 ml 0.01 M phosphate buffer H 6.9 and mixed with 0.5 ml pyridine. The mixture was layered on 0.2 ml benzenesulfonyl chloride. The reaction was started by mixing for one min with a mechanical shaker. The colored solution was allowed to stand for 30 min, diluted with 5 ml ethanol, and absorbance measured at 410 nm within 30 min after the dilution. The coefficient of variation of this method was 6% and the recovery 103% when urine contains about 0.2-0.5 mg hippuric acid per ml of urine. The concentration was linear up to 2.0 mg per ml hippuric acid in a specimen."}
{"id": "PMID:22219", "title": "Antibacterial effect, plasmid curing activity and chemical structure of some tricyclic compounds.", "content": "Diethazine, amitriptyline and imipramine showed bacteriostatic and bactericidal effect on different bacteria. Chlorpromazine sulphoxide and fluorescein were ineffective even at 1000 microgram/ml. The antibacterial compounds deleted at 40-70% frequency the F'lac plasmid of Escherichia coli K12 LE-140.", "contents": "Antibacterial effect, plasmid curing activity and chemical structure of some tricyclic compounds. Diethazine, amitriptyline and imipramine showed bacteriostatic and bactericidal effect on different bacteria. Chlorpromazine sulphoxide and fluorescein were ineffective even at 1000 microgram/ml. The antibacterial compounds deleted at 40-70% frequency the F'lac plasmid of Escherichia coli K12 LE-140."}
{"id": "PMID:22226", "title": "Inhibition of transmitter release from isolated rabbit kidney by bradykinin.", "content": "The effect of kallikrein on the release of norepinephrine has been studied in the isolated perfused rabbit kidney. Kallikrein in the perfusion medium caused an inhibition in the rise of the perfusion pressure induced by periarterial stimulation and in the contraction of rabbit aorta superfused by the venous outflow of the stimulated kidney. On the contrary, kallikrein caused a potentiation in the urine volume induced by periarterial stimulation. Similar findings were obtained when bradykinin was added instead of kallikrein. Kallikrein did not alter the pressure response and rabbit aorta contraction but potentiated the diuretic effects of exogenously administered norepinephrine. Acetyl salicyclic acid when added to the perfusion medium containing kallikrein caused a reversal in all parameters measured in this study. It is concluded that the changes of the effects of periarterial stimulation of the isolated rabbit kidney by kallikrein are mediated through the bradykinin-mediated increased generation of intrarenal prostaglandins.", "contents": "Inhibition of transmitter release from isolated rabbit kidney by bradykinin. The effect of kallikrein on the release of norepinephrine has been studied in the isolated perfused rabbit kidney. Kallikrein in the perfusion medium caused an inhibition in the rise of the perfusion pressure induced by periarterial stimulation and in the contraction of rabbit aorta superfused by the venous outflow of the stimulated kidney. On the contrary, kallikrein caused a potentiation in the urine volume induced by periarterial stimulation. Similar findings were obtained when bradykinin was added instead of kallikrein. Kallikrein did not alter the pressure response and rabbit aorta contraction but potentiated the diuretic effects of exogenously administered norepinephrine. Acetyl salicyclic acid when added to the perfusion medium containing kallikrein caused a reversal in all parameters measured in this study. It is concluded that the changes of the effects of periarterial stimulation of the isolated rabbit kidney by kallikrein are mediated through the bradykinin-mediated increased generation of intrarenal prostaglandins."}
{"id": "PMID:22228", "title": "Translation by bacterial cells of messenger RNA for interferon of animal origin.", "content": "Escherichia coli, strain AB 1157, cells are capable of translating human, mouse, and chicken messenter RNA for interferon with production of interferon of the corresponding specifity. This translation occurs in the presence of serum. The activity of the resulting interferon decreased in parallel to dilution of the original mRNA preparation, upon multiple ulitization of the mRNA solution, as well as upon reduction of the interferon- producing activity of cells-donors of mRNA due to prolonged storage of the cells. Unlike animal cells, the bacteria do not require pre-treatment with actinomycin D. The interferon translated by bacteria is inactivated by trypsin and resistant to ribonuclease.", "contents": "Translation by bacterial cells of messenger RNA for interferon of animal origin. Escherichia coli, strain AB 1157, cells are capable of translating human, mouse, and chicken messenter RNA for interferon with production of interferon of the corresponding specifity. This translation occurs in the presence of serum. The activity of the resulting interferon decreased in parallel to dilution of the original mRNA preparation, upon multiple ulitization of the mRNA solution, as well as upon reduction of the interferon- producing activity of cells-donors of mRNA due to prolonged storage of the cells. Unlike animal cells, the bacteria do not require pre-treatment with actinomycin D. The interferon translated by bacteria is inactivated by trypsin and resistant to ribonuclease."}
{"id": "PMID:22229", "title": "Physico-chemical properties of interferon produced by a mixed leukocyte suspension.", "content": "Physico-chemical properties of partially purified interferon produced by a mixed culture of human peripheral blood leukocytes following induction with double-stranded RNA extracted from f2 phage infected Escherichia coli were studied. Molecular heterogeneity of the interferon preparation was demonstrated by gel chromatography on a Sephadex G-100 column, disc electrophoresis in polyacrylamide gel and by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The first two methods revealed 5 peaks, the latter 7 peaks of interferon activity. There was no difference in the molecular nature of interferon produced by cultures exposed to the inducer for the whole period of incubation and that produced by cultures from which the inducer was removed after a short induction time.", "contents": "Physico-chemical properties of interferon produced by a mixed leukocyte suspension. Physico-chemical properties of partially purified interferon produced by a mixed culture of human peripheral blood leukocytes following induction with double-stranded RNA extracted from f2 phage infected Escherichia coli were studied. Molecular heterogeneity of the interferon preparation was demonstrated by gel chromatography on a Sephadex G-100 column, disc electrophoresis in polyacrylamide gel and by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The first two methods revealed 5 peaks, the latter 7 peaks of interferon activity. There was no difference in the molecular nature of interferon produced by cultures exposed to the inducer for the whole period of incubation and that produced by cultures from which the inducer was removed after a short induction time."}
{"id": "PMID:22230", "title": "Effect of amino acid replacement on the stability of the tobacco mosaic virus protein structure.", "content": "A comparative polarographic study on the alkaline degradation of tobacco mosaic virus (TMV) strain vulgare and its mutant TMV 483, having histidine instead of glutamine at position 9 in the polypeptide chain, was performed. In the course of alkaline degradation and subsequent incubation in the supporting electrolyte at 0 degrees C TMV 483, unlike TMV vulgare, showed a polarographic effect indicating the unfolding of the TMV polypeptide. It was concluded that the replacement of glutamine-9 by histidine causes a decrease in the stability of the three-dimensional structure of the TMV protein subunit. A polarographic study of untreated virions as well as denatured proteins of both TMV strains showed that histidine, when incorporated into the polypeptide chain, is not active polarographically at the conditions used.", "contents": "Effect of amino acid replacement on the stability of the tobacco mosaic virus protein structure. A comparative polarographic study on the alkaline degradation of tobacco mosaic virus (TMV) strain vulgare and its mutant TMV 483, having histidine instead of glutamine at position 9 in the polypeptide chain, was performed. In the course of alkaline degradation and subsequent incubation in the supporting electrolyte at 0 degrees C TMV 483, unlike TMV vulgare, showed a polarographic effect indicating the unfolding of the TMV polypeptide. It was concluded that the replacement of glutamine-9 by histidine causes a decrease in the stability of the three-dimensional structure of the TMV protein subunit. A polarographic study of untreated virions as well as denatured proteins of both TMV strains showed that histidine, when incorporated into the polypeptide chain, is not active polarographically at the conditions used."}
{"id": "PMID:22231", "title": "Ultrastructural studies of cell-virus interaction in reptilian cell lines. IV. Effects of chloramphenicol and ethidium bromide on VSW cell mitochondria and associated virions.", "content": "Structural effects of chloramphenicol (CAP) and ethidium bromide (EB) on VSW cell mitochondria and intramitochondrial virions (IMV) have been studied on a comparative basis by thin-section electron microscopy. CAP-treated cells show a wide variety of mitochondrial alterations, frequently involving swelling of the organelle and loss of cristae orientation. IMV are generally severely disrupted, particularly in peripheral regions. In such configurations, strand-like material radiates in a spokelike fashion from the shell zone to adjacent cristae-matrix area. EB-treated cells also display considerable mitochondrial distortion evidenced primarily by the formation of small, localized multimembrane regions. IMV exposed to EB, however, are less structurally damaged than CAP-treated ones. The relative incidence of IMV production is enhanced approximately fourfold in EB-treated cells compared to CAP-treated ones, suggesting that virion synthesis may be under nuclear, rather than mitochondrial, control.", "contents": "Ultrastructural studies of cell-virus interaction in reptilian cell lines. IV. Effects of chloramphenicol and ethidium bromide on VSW cell mitochondria and associated virions. Structural effects of chloramphenicol (CAP) and ethidium bromide (EB) on VSW cell mitochondria and intramitochondrial virions (IMV) have been studied on a comparative basis by thin-section electron microscopy. CAP-treated cells show a wide variety of mitochondrial alterations, frequently involving swelling of the organelle and loss of cristae orientation. IMV are generally severely disrupted, particularly in peripheral regions. In such configurations, strand-like material radiates in a spokelike fashion from the shell zone to adjacent cristae-matrix area. EB-treated cells also display considerable mitochondrial distortion evidenced primarily by the formation of small, localized multimembrane regions. IMV exposed to EB, however, are less structurally damaged than CAP-treated ones. The relative incidence of IMV production is enhanced approximately fourfold in EB-treated cells compared to CAP-treated ones, suggesting that virion synthesis may be under nuclear, rather than mitochondrial, control."}
{"id": "PMID:22232", "title": "Genetic characteristics of clones derived from measles virus strain L-16.", "content": "The L-16 vaccine strain of measles virus produced in L-41 cell cultures of various size (0.5-0.2 mm in diameter), with clear or opaque centers, thus being genetically heterogeneous by the S and P markes. The clones derived from the L-16 strain differed from it and from each other in a number of genetic properties. Clones isolated at different temperatures, 35 degrees or 32 degrees C, differed from each other in thermostability, sensitivity to interferon, interferon-inducing activity, antigenicity and plaque size. Marked correlations were established between cytopathic activity (TC) and reproductive activity in L-41 cell cultures; thermostability at 50 degrees C (T50 character) and inactivation constant; and interferon-inducing activity and sensitivity to interferon.", "contents": "Genetic characteristics of clones derived from measles virus strain L-16. The L-16 vaccine strain of measles virus produced in L-41 cell cultures of various size (0.5-0.2 mm in diameter), with clear or opaque centers, thus being genetically heterogeneous by the S and P markes. The clones derived from the L-16 strain differed from it and from each other in a number of genetic properties. Clones isolated at different temperatures, 35 degrees or 32 degrees C, differed from each other in thermostability, sensitivity to interferon, interferon-inducing activity, antigenicity and plaque size. Marked correlations were established between cytopathic activity (TC) and reproductive activity in L-41 cell cultures; thermostability at 50 degrees C (T50 character) and inactivation constant; and interferon-inducing activity and sensitivity to interferon."}
{"id": "PMID:22233", "title": "Influenza virus antigens in human leukocytes after oral administration of live tissue culture influenza A monovaccine.", "content": "Influenza A virus antigens were detected in leukocytes by immunofluorescence. After intravenous inoculation of the A/Moscow/16/65 (H2N2) vaccine strain to chickens, cytoplasmic antigens of the virus were observed in mononuclear leukocytes from 24 to 72 hours post inoculation (p.i.). The course of antigen detectability was similar after two repeated inoculations of the virus. After oral vaccination of human volunteers with a live tissue culture influenza A monovaccine from the X-47 (H3N2) recombinant viral antigens were also found in mononuclears; the maximal number of antigen-positive cells was observed at 24 hours p.i. The method of membrane immunofluorescence proved to be the most sensitive for antigen detection; it revealed a considerable decrease in the number of antigen-positive cells after repeated administration of the virus to volunteers. This fact may possibly reflect the development of antiviral resistance in the process of vaccination.", "contents": "Influenza virus antigens in human leukocytes after oral administration of live tissue culture influenza A monovaccine. Influenza A virus antigens were detected in leukocytes by immunofluorescence. After intravenous inoculation of the A/Moscow/16/65 (H2N2) vaccine strain to chickens, cytoplasmic antigens of the virus were observed in mononuclear leukocytes from 24 to 72 hours post inoculation (p.i.). The course of antigen detectability was similar after two repeated inoculations of the virus. After oral vaccination of human volunteers with a live tissue culture influenza A monovaccine from the X-47 (H3N2) recombinant viral antigens were also found in mononuclears; the maximal number of antigen-positive cells was observed at 24 hours p.i. The method of membrane immunofluorescence proved to be the most sensitive for antigen detection; it revealed a considerable decrease in the number of antigen-positive cells after repeated administration of the virus to volunteers. This fact may possibly reflect the development of antiviral resistance in the process of vaccination."}
{"id": "PMID:22234", "title": "Isolation and preliminary characterization of temperature-sensitive mutants of pseudorabies virus.", "content": "Nine ts mutants of pseudorabies virus (PRV) strain BUK were isolated following bromodeoxyuridine (BUdR) or NaNO2 mutagenesis by a selection technique based on a shiftdown from nonpermissive to permissive temperature. This technique is described and its advantages are discussed. The nine ts mutants have been assigned to four complementation groups.", "contents": "Isolation and preliminary characterization of temperature-sensitive mutants of pseudorabies virus. Nine ts mutants of pseudorabies virus (PRV) strain BUK were isolated following bromodeoxyuridine (BUdR) or NaNO2 mutagenesis by a selection technique based on a shiftdown from nonpermissive to permissive temperature. This technique is described and its advantages are discussed. The nine ts mutants have been assigned to four complementation groups."}
{"id": "PMID:22235", "title": "Measurement of antibodies to herpesvirus types 1 and 2 in human sera by microradioimmunoassay.", "content": "The binding of 125I-labelled anti-human antibodies against the fc IgG fragment to unlabelled antiviral immunoglobulins in the surface of infected cells was used to quantitate antibodies against herpes simplex virus type (HSV-1) and type 2 (HSV-2) in sera from patients with cervix carcinoma. The microradioimmunoassay technique (micro-RIA) proved to be 5-10 times more sensitive than the microneutralization test. Antibody titres determined by micro-RIA correlated with neutralizing antibody titres to both HSV-1 and HSV-2. The relative antibody titres to HSV-1 and HSV-2, as determined by micro-RIA, could be used to distinguish persons previously infected with HSV-2 by means of II/I indices.", "contents": "Measurement of antibodies to herpesvirus types 1 and 2 in human sera by microradioimmunoassay. The binding of 125I-labelled anti-human antibodies against the fc IgG fragment to unlabelled antiviral immunoglobulins in the surface of infected cells was used to quantitate antibodies against herpes simplex virus type (HSV-1) and type 2 (HSV-2) in sera from patients with cervix carcinoma. The microradioimmunoassay technique (micro-RIA) proved to be 5-10 times more sensitive than the microneutralization test. Antibody titres determined by micro-RIA correlated with neutralizing antibody titres to both HSV-1 and HSV-2. The relative antibody titres to HSV-1 and HSV-2, as determined by micro-RIA, could be used to distinguish persons previously infected with HSV-2 by means of II/I indices."}
{"id": "PMID:22236", "title": "Infectivity of DNA recovered from cells persistently infected with SV5 paramyxovirus.", "content": "Infectivity of DNA isolated from L cells chronically infected with SV5 paramyxovirus was demonstrated by inoculation of continuous RH and HEp-2 cells. Infectivity of the DNA was completely abolished by treatment with deoxyribonuclease or by alkaline hydrolysis but did not change after treatment with ribonuclease and specific anti SV5 serum. The virus obtained as a result of transfection caused haemadsorption in susceptible cells and was neutralized by specific antiserum like the prototype SV5 strain.", "contents": "Infectivity of DNA recovered from cells persistently infected with SV5 paramyxovirus. Infectivity of DNA isolated from L cells chronically infected with SV5 paramyxovirus was demonstrated by inoculation of continuous RH and HEp-2 cells. Infectivity of the DNA was completely abolished by treatment with deoxyribonuclease or by alkaline hydrolysis but did not change after treatment with ribonuclease and specific anti SV5 serum. The virus obtained as a result of transfection caused haemadsorption in susceptible cells and was neutralized by specific antiserum like the prototype SV5 strain."}
{"id": "PMID:22237", "title": "Mononuclear cells in Japanese encephalitis virus infection: changes in cells counts and specific fluorescence.", "content": "Progressive reduction in blood cell counts was observed in mice inoculated intracerebrally (ic) with Japanese encephalitis (JE) virus. No changes were observed in the blood cell counts of mice inoculated intraperitoneally (ip). Reduction in cell counts after a transient rise was noticed in lymph nodes of mice inoculated by either route but the cell counts returned to normal in lymph nodes of ip inoculated mice by the 8th day post inoculation (p.i.). JE virus antigen was demonstrated by immunofluorescence in mononuclear cells from the blood, spleen and lymph nodes starting from the 3rd and 4th day p.i. in mice inoculated ic and ip, respectively. The number of fluorescent cells increased as the infection progressed. The number of fluorescent spleen cells uas higher in ip than in ic inoculated mice. Live virus could only occasionally be demonstrated in the cells.", "contents": "Mononuclear cells in Japanese encephalitis virus infection: changes in cells counts and specific fluorescence. Progressive reduction in blood cell counts was observed in mice inoculated intracerebrally (ic) with Japanese encephalitis (JE) virus. No changes were observed in the blood cell counts of mice inoculated intraperitoneally (ip). Reduction in cell counts after a transient rise was noticed in lymph nodes of mice inoculated by either route but the cell counts returned to normal in lymph nodes of ip inoculated mice by the 8th day post inoculation (p.i.). JE virus antigen was demonstrated by immunofluorescence in mononuclear cells from the blood, spleen and lymph nodes starting from the 3rd and 4th day p.i. in mice inoculated ic and ip, respectively. The number of fluorescent cells increased as the infection progressed. The number of fluorescent spleen cells uas higher in ip than in ic inoculated mice. Live virus could only occasionally be demonstrated in the cells."}
{"id": "PMID:22238", "title": "Search for correlates of resistance to virulent challenge in mice immunized with Coxiella burnetii.", "content": "Mice immunized with live phase I or phase II Coxiella burnetii, with killed phase I or phase II organisms or with trichloroacetic acid (TCAE) or phenol (PE) extracts were resistant to intraperitoneal infection with phase I C. burnetii irrespective of whether or not they displayed phase I antibody response at the time of virulent challenge. Increased phagocytosis of purified phase I organisms by blood leukocytes or peritoneal exudate cells (PEC) was noticed only in mice with phase I agglutinating antibodies in their sera or peritoneal washings. Passive transfer of resistance was made possible only by sera containing phase I agglutinating antibodies. Adoptive transfer of immunity by spleen cells, but not by PEC, was achieved providing that these cells were taken from mice immunized with live phase I C. burnetii.", "contents": "Search for correlates of resistance to virulent challenge in mice immunized with Coxiella burnetii. Mice immunized with live phase I or phase II Coxiella burnetii, with killed phase I or phase II organisms or with trichloroacetic acid (TCAE) or phenol (PE) extracts were resistant to intraperitoneal infection with phase I C. burnetii irrespective of whether or not they displayed phase I antibody response at the time of virulent challenge. Increased phagocytosis of purified phase I organisms by blood leukocytes or peritoneal exudate cells (PEC) was noticed only in mice with phase I agglutinating antibodies in their sera or peritoneal washings. Passive transfer of resistance was made possible only by sera containing phase I agglutinating antibodies. Adoptive transfer of immunity by spleen cells, but not by PEC, was achieved providing that these cells were taken from mice immunized with live phase I C. burnetii."}
{"id": "PMID:22239", "title": "Massive occurrence of rickettsiae of the spotted fever group in fowl tampan, Argas persicus, in the Armenian S.S.R.", "content": "Fowl tampans (Argas persicus) collected in Oktemberyan in the Armenian S.S.R. in 1974 were found to be massively infected with rickettsiae of the spotted fever (SF) group. One isolated rickettsial strain, designated Armenia 9, is antigenically related to, and probably identical with, strain Armenia 11 and strain B of Rickettsia slovaca, isolated from Dermacentor marginatus ticks. Strain Armenia 9 grows readily in chick embryo yolk sacs and in chick embryo cell (CEC) and L-cell cultures. It causes generalized infection in both soft and hard ticks. A fatal disease was produced in Clethrionomys glareolus after subcutaneous inoculation. Similar inoculation of other small wild rodents (Mus musculus, Microtus arvalis, Apodemus flavicollis), hens and laboratory animals (guinea pigs, white mice and hamsters) resulted only in an antibody response.", "contents": "Massive occurrence of rickettsiae of the spotted fever group in fowl tampan, Argas persicus, in the Armenian S.S.R. Fowl tampans (Argas persicus) collected in Oktemberyan in the Armenian S.S.R. in 1974 were found to be massively infected with rickettsiae of the spotted fever (SF) group. One isolated rickettsial strain, designated Armenia 9, is antigenically related to, and probably identical with, strain Armenia 11 and strain B of Rickettsia slovaca, isolated from Dermacentor marginatus ticks. Strain Armenia 9 grows readily in chick embryo yolk sacs and in chick embryo cell (CEC) and L-cell cultures. It causes generalized infection in both soft and hard ticks. A fatal disease was produced in Clethrionomys glareolus after subcutaneous inoculation. Similar inoculation of other small wild rodents (Mus musculus, Microtus arvalis, Apodemus flavicollis), hens and laboratory animals (guinea pigs, white mice and hamsters) resulted only in an antibody response."}
{"id": "PMID:22240", "title": "Some biological properties of an endotoxic lipopolysaccharide from the typhus group rickettsiae.", "content": "A lipophilic thermostable lipopolysaccharide (LPS) complex was isolated by phenol extraction from purified suspensions of the typhus group rickettsiae. The LPS complex is antigenic and possesses some endotoxic properties such as toxicity for actinomycin D-treated mice, pyrogenicity for rabbits and guinea pigs, ability to elicit hypothermia in white rats and local Schwartzman reaction and active cutaneous anaphylaxis in rabbits.", "contents": "Some biological properties of an endotoxic lipopolysaccharide from the typhus group rickettsiae. A lipophilic thermostable lipopolysaccharide (LPS) complex was isolated by phenol extraction from purified suspensions of the typhus group rickettsiae. The LPS complex is antigenic and possesses some endotoxic properties such as toxicity for actinomycin D-treated mice, pyrogenicity for rabbits and guinea pigs, ability to elicit hypothermia in white rats and local Schwartzman reaction and active cutaneous anaphylaxis in rabbits."}
{"id": "PMID:22243", "title": "Effects of ethanol on electrical parameters of the in vivo rat stomach.", "content": "The gastric transmural electrical potential difference (PD) and direct-current resistance were measured in the rat in vivo under conditions in which the luminal pH was controlled over the pH range 1.0 to 12.0. Raising the pH above 11.0 caused a reduction in both PD and resistance. This is consistent with basic groups limiting cation permeability through the mucosa. Exposure of the mucosa to 20% ethanol caused a reduction in resistance, PD, and H+ secretion, and an increased appearance of Na+ in the lumen at neutral pH. The pH dependence of the resistance at high pH values was also eliminated, consistent with the elimination or bypassing of channels containing basic groups. Mucosal exposure to 8.5% ethanol reduced the PD and H+ secretion without affecting resistance. The increased appearance of Na+ in the lumen seen with this alcohol solution also occurred following exposure to hyperosmotic sucrose.", "contents": "Effects of ethanol on electrical parameters of the in vivo rat stomach. The gastric transmural electrical potential difference (PD) and direct-current resistance were measured in the rat in vivo under conditions in which the luminal pH was controlled over the pH range 1.0 to 12.0. Raising the pH above 11.0 caused a reduction in both PD and resistance. This is consistent with basic groups limiting cation permeability through the mucosa. Exposure of the mucosa to 20% ethanol caused a reduction in resistance, PD, and H+ secretion, and an increased appearance of Na+ in the lumen at neutral pH. The pH dependence of the resistance at high pH values was also eliminated, consistent with the elimination or bypassing of channels containing basic groups. Mucosal exposure to 8.5% ethanol reduced the PD and H+ secretion without affecting resistance. The increased appearance of Na+ in the lumen seen with this alcohol solution also occurred following exposure to hyperosmotic sucrose."}
{"id": "PMID:22244", "title": "Gastric mucosal damage by taurine and glycine conjugates of chenodeoxycholic acid.", "content": "Bile damage to gastric mucosa may be demonstrated by means of changes in the transmucosal movement of H+ and Na+ ions. In the present study pure 10 mM solutions of taurine and glycine conjugates of chenodeoxycholic acid were instilled into canine Heidenhain pouches. Solutions were prepared at pH 2, 4, and 8, as previous work had shown a greater damaging effect at low pH. The present study confirmed this pH effect, but only with respect to movement of Na+ ion for taurine conjugates. The magnitude of the changes in ionic movements was much greater with pure bile acid solutions than that seen previously with whole bile. These findings are discussed. The greater damage seen below the pKa of the bile acid conjugates suggests that its nonionized form is the more damaging.", "contents": "Gastric mucosal damage by taurine and glycine conjugates of chenodeoxycholic acid. Bile damage to gastric mucosa may be demonstrated by means of changes in the transmucosal movement of H+ and Na+ ions. In the present study pure 10 mM solutions of taurine and glycine conjugates of chenodeoxycholic acid were instilled into canine Heidenhain pouches. Solutions were prepared at pH 2, 4, and 8, as previous work had shown a greater damaging effect at low pH. The present study confirmed this pH effect, but only with respect to movement of Na+ ion for taurine conjugates. The magnitude of the changes in ionic movements was much greater with pure bile acid solutions than that seen previously with whole bile. These findings are discussed. The greater damage seen below the pKa of the bile acid conjugates suggests that its nonionized form is the more damaging."}
{"id": "PMID:22246", "title": "Endocrine cells of bronchial and bronchiolar epithelium.", "content": "Among the epithelial elements of the pulmonary airways are cells with features suggestive of endocrine function. Although these cells share a number of properties with the intestinal endocrine (argentaffine) cells, peptide hormones analogous to the multitude of those present in the gastrointestinal tract have yet to be identified in the lung. The oat cell carcinoma, which arises from this cell type, is of importance clinically, yet investigations into the basic properties and functions of this cell have been difficult and sparse, in part due to a lack of appreciation of the problem.", "contents": "Endocrine cells of bronchial and bronchiolar epithelium. Among the epithelial elements of the pulmonary airways are cells with features suggestive of endocrine function. Although these cells share a number of properties with the intestinal endocrine (argentaffine) cells, peptide hormones analogous to the multitude of those present in the gastrointestinal tract have yet to be identified in the lung. The oat cell carcinoma, which arises from this cell type, is of importance clinically, yet investigations into the basic properties and functions of this cell have been difficult and sparse, in part due to a lack of appreciation of the problem."}
{"id": "PMID:22247", "title": "Fetal reacting bradycardia.", "content": "Acute and abrupt fetal bradycardia are considered to be vagal in origin. In addition to head compression and funis compression bradycardias, we will report on those acute fetal bradycardias occurring during maternal seizures and maternal voiding, during aortocaval compression, during terminal labor, and during the immediate postpartum period. While certain mechanisms are known which can explain some or parts of these bradycardias, we conclude that in the clinical setting information is insufficient to determine their etiology with precision. Instead of labeling abrupt fetal heart rate pattern as resulting from either head or funis compression, it is suggested that the patterns be described according to their severity and duration. Such acute fetal bradycardias can be detrimental in terms of reduced umbilical flow. Administration of atropine may be indicated in the otherwise healthy fetus with acute bradycardia.", "contents": "Fetal reacting bradycardia. Acute and abrupt fetal bradycardia are considered to be vagal in origin. In addition to head compression and funis compression bradycardias, we will report on those acute fetal bradycardias occurring during maternal seizures and maternal voiding, during aortocaval compression, during terminal labor, and during the immediate postpartum period. While certain mechanisms are known which can explain some or parts of these bradycardias, we conclude that in the clinical setting information is insufficient to determine their etiology with precision. Instead of labeling abrupt fetal heart rate pattern as resulting from either head or funis compression, it is suggested that the patterns be described according to their severity and duration. Such acute fetal bradycardias can be detrimental in terms of reduced umbilical flow. Administration of atropine may be indicated in the otherwise healthy fetus with acute bradycardia."}
{"id": "PMID:22248", "title": "Intrapartum fetal asphyxia: clinical characteristics, diagnosis, and significance in relation to pattern of development.", "content": "The clinical and fetal heart rates and acid-base characteristics and their sequelae have been reviewed in 587 patients. The relevant clinical factors in the asphyxia group were the preterm fetus, the intrauterine growth retarded fetus, maternal toxemia, and midforceps delivery. The duration of the developing metabolic acidosis in the asphyxia group ranged from terminal to the last two hours of labor. Marked patterns of total decelerations and moderate and marked patterns of late decelerations are of predictive value in the diagnosis of intrapartum fetal asphyxia with a trend to an increased incidence in the longer duration categories, between four and two hours prior to delivery, and a significant increase in all categories during the last two hours of labor. The significance of intrapartum fetal asphyxia to the newborn infant is evident from the low Apgar scores, increased incidence of moderate and severe respiratory distress syndrome, and central nervous system complications in the asphixia group in relation to the normal group.", "contents": "Intrapartum fetal asphyxia: clinical characteristics, diagnosis, and significance in relation to pattern of development. The clinical and fetal heart rates and acid-base characteristics and their sequelae have been reviewed in 587 patients. The relevant clinical factors in the asphyxia group were the preterm fetus, the intrauterine growth retarded fetus, maternal toxemia, and midforceps delivery. The duration of the developing metabolic acidosis in the asphyxia group ranged from terminal to the last two hours of labor. Marked patterns of total decelerations and moderate and marked patterns of late decelerations are of predictive value in the diagnosis of intrapartum fetal asphyxia with a trend to an increased incidence in the longer duration categories, between four and two hours prior to delivery, and a significant increase in all categories during the last two hours of labor. The significance of intrapartum fetal asphyxia to the newborn infant is evident from the low Apgar scores, increased incidence of moderate and severe respiratory distress syndrome, and central nervous system complications in the asphixia group in relation to the normal group."}
{"id": "PMID:22252", "title": "The rodent as an experimental tool in gerontological research.", "content": "Advances in basic gerontology has has brought along numerous methodological questions among which the growth-persistency as a function of ageing of the rodents, particularly the rat, plays an intriguing role. The fact that, the rat's growth may proceed for more than half of the lifetime was confirmed by many authors. Whether the senescent loss in body weight is induced by the subnormal food and water intake in old age, or rather, the former leads to the latter, has not yet settled. It is suggested however, that the apparent detrimental losses in masticatory function; i.e. defects of the maxillary incisors of the aged animals exert food consumption by all accounts. This can be either the consequence or cause of the unessential loss of body weight well before death. The reasons which explain the startling pecularity concerned of the rodents must be sought in the phylogenetical backgrounds of these species. Most of them are still in their flourishing-evolutionary period of the present. These small-sized, omnivorous, highly-variable animals are non-specialized but labile/flexible species to convert according to our requirements. Neverthless, particular attention should be paid when treating these animals, as rather primordial species, whose one or more characteristics, i.e. persistency in growth merit a special caution of gerontologists.", "contents": "The rodent as an experimental tool in gerontological research. Advances in basic gerontology has has brought along numerous methodological questions among which the growth-persistency as a function of ageing of the rodents, particularly the rat, plays an intriguing role. The fact that, the rat's growth may proceed for more than half of the lifetime was confirmed by many authors. Whether the senescent loss in body weight is induced by the subnormal food and water intake in old age, or rather, the former leads to the latter, has not yet settled. It is suggested however, that the apparent detrimental losses in masticatory function; i.e. defects of the maxillary incisors of the aged animals exert food consumption by all accounts. This can be either the consequence or cause of the unessential loss of body weight well before death. The reasons which explain the startling pecularity concerned of the rodents must be sought in the phylogenetical backgrounds of these species. Most of them are still in their flourishing-evolutionary period of the present. These small-sized, omnivorous, highly-variable animals are non-specialized but labile/flexible species to convert according to our requirements. Neverthless, particular attention should be paid when treating these animals, as rather primordial species, whose one or more characteristics, i.e. persistency in growth merit a special caution of gerontologists."}
{"id": "PMID:22253", "title": "[Polyploidisation - a phenomenon of aging? (author's transl)].", "content": "By means of cytophotometric determination of DNA in different cellular systems an increase in polyploidisation correlated to age could be demonstrated. The latter is well demonstrable if compensatory hyperplasia or hypertrophy occurs. It is discussed that cellular systems of older individuals can increase their DNA - content, but they are not able to carry out a caryo-and cytocinesis.", "contents": "[Polyploidisation - a phenomenon of aging? (author's transl)]. By means of cytophotometric determination of DNA in different cellular systems an increase in polyploidisation correlated to age could be demonstrated. The latter is well demonstrable if compensatory hyperplasia or hypertrophy occurs. It is discussed that cellular systems of older individuals can increase their DNA - content, but they are not able to carry out a caryo-and cytocinesis."}
{"id": "PMID:22254", "title": "[Tensibility measurements on the rats aorta (author's transl)].", "content": "II. Elasticity Parameters in Various Ages Power-extension diagrams of longitudinal and transversal stripes of the Aorta thoracica were recorded by means of an elctro-mechanical measuring instrument. The samples were taken from 108 male Sprague-Dawley rats aged 9, 15 and 24 months. The following parameters describing age-dependent alterations were calculated from the hysteresis loops of three consecutive extension-relaxation cycles: 1. the maximum power 2. the area of the first hysteresis loop 3. the characteristic of the relaxation-part of the third cycle. The maximum power and partly the areas of the hysteresis loops increased with age. The curves obtained by longitudinal stripes were approximated to a linear function (y = a + bx) plus a power-function (y = cxd). Their constants were explained as indices to the plasticity of the aorta, the retraction-power of the elastic fibres, the degree of the spiralization of the collagen fibres and the amount and/or the stability of the collagen. The ageing changes of these parameters indicated an increase of plasticity, an increase in the retraction-power of the elastic fibres, a rise of the pitch of the collagen spiral and an increase in the amount and/or in the stability of collagen. The curves from the extension of the transversal stripes revealed a different extension characteristic and could be described as the sum of two power functions. The causes of this different behaviour are not yet clearly understood.", "contents": "[Tensibility measurements on the rats aorta (author's transl)]. II. Elasticity Parameters in Various Ages Power-extension diagrams of longitudinal and transversal stripes of the Aorta thoracica were recorded by means of an elctro-mechanical measuring instrument. The samples were taken from 108 male Sprague-Dawley rats aged 9, 15 and 24 months. The following parameters describing age-dependent alterations were calculated from the hysteresis loops of three consecutive extension-relaxation cycles: 1. the maximum power 2. the area of the first hysteresis loop 3. the characteristic of the relaxation-part of the third cycle. The maximum power and partly the areas of the hysteresis loops increased with age. The curves obtained by longitudinal stripes were approximated to a linear function (y = a + bx) plus a power-function (y = cxd). Their constants were explained as indices to the plasticity of the aorta, the retraction-power of the elastic fibres, the degree of the spiralization of the collagen fibres and the amount and/or the stability of the collagen. The ageing changes of these parameters indicated an increase of plasticity, an increase in the retraction-power of the elastic fibres, a rise of the pitch of the collagen spiral and an increase in the amount and/or in the stability of collagen. The curves from the extension of the transversal stripes revealed a different extension characteristic and could be described as the sum of two power functions. The causes of this different behaviour are not yet clearly understood."}
{"id": "PMID:22255", "title": "Long-term tryptophan restriction and aging in the rat.", "content": "Growth-retarded rats fed a tryptophan deficient diet at 21 days for periods of 6-22 months were shown to reach normal body weight when subsequently fed Purina Rat Chow. They demonstrated an increased ability over similar aged controls to recover from hypothermia induced by 3-minute whole-body ice water immersion, were able to bear litters at 17--28 months of age, showed a delay in the age of onset of visible tumors, and indicated an increase in their average lifespan at late ages. Animals fed on this diet from 3 months of age revealed a similar ability to reproduce at advanced ages, but not as marked as those placed on the diet earlier. The average lifespan (in months +/- the standard error of the mean) of the rats recovering from the long-term tryptophan-deficient diets was 36.31 +/- 2.26 while the control rats survived an average of 30.5 +/- 1.90 months. The last of 8 rats surviving the period of tryptophan-deficiency died at 45.50 months (1387 days) while the last of 14 control rats died at 41.75 months (1266 days). It is hypothesized that some kind of subtle mechanism exerts its influence on the rats during the period of tryptophan deficiency which caused an accelerated morbidity and mortality as they approached senescence approximately 1 to 2 years after refeeding. This is parallel to the situation with immature animals subjected to long-term caloric restriction and then fed on normal diets.", "contents": "Long-term tryptophan restriction and aging in the rat. Growth-retarded rats fed a tryptophan deficient diet at 21 days for periods of 6-22 months were shown to reach normal body weight when subsequently fed Purina Rat Chow. They demonstrated an increased ability over similar aged controls to recover from hypothermia induced by 3-minute whole-body ice water immersion, were able to bear litters at 17--28 months of age, showed a delay in the age of onset of visible tumors, and indicated an increase in their average lifespan at late ages. Animals fed on this diet from 3 months of age revealed a similar ability to reproduce at advanced ages, but not as marked as those placed on the diet earlier. The average lifespan (in months +/- the standard error of the mean) of the rats recovering from the long-term tryptophan-deficient diets was 36.31 +/- 2.26 while the control rats survived an average of 30.5 +/- 1.90 months. The last of 8 rats surviving the period of tryptophan-deficiency died at 45.50 months (1387 days) while the last of 14 control rats died at 41.75 months (1266 days). It is hypothesized that some kind of subtle mechanism exerts its influence on the rats during the period of tryptophan deficiency which caused an accelerated morbidity and mortality as they approached senescence approximately 1 to 2 years after refeeding. This is parallel to the situation with immature animals subjected to long-term caloric restriction and then fed on normal diets."}
{"id": "PMID:22256", "title": "The age dependence of bile acid metabolism in rats.", "content": "The age dependence of bile acid metabolism in rats was investigated and the following results were obtained. 1) Synthesis rate, pool size and total secretion decreased in old rats (24 month) significantly compared to young rats (6 weeks). 2) The quotient of taurine to glycine conjugates is is significant lower in old rats compared to young rats. 3) The lithogenic index remains unchanged in all age groups. 4) Old rats show a significantly higher Km for cholic acid uptake, whereas the diffusion coefficient is decreased. The possible influence of humoral factors on age dependent regulations of bile metabolism is discussed.", "contents": "The age dependence of bile acid metabolism in rats. The age dependence of bile acid metabolism in rats was investigated and the following results were obtained. 1) Synthesis rate, pool size and total secretion decreased in old rats (24 month) significantly compared to young rats (6 weeks). 2) The quotient of taurine to glycine conjugates is is significant lower in old rats compared to young rats. 3) The lithogenic index remains unchanged in all age groups. 4) Old rats show a significantly higher Km for cholic acid uptake, whereas the diffusion coefficient is decreased. The possible influence of humoral factors on age dependent regulations of bile metabolism is discussed."}
{"id": "PMID:22257", "title": "Age-dependent changes of the protein synthetic machinery of liver cell cytoplasm as revealed by electron microscopic morphometry.", "content": "Complete electron microscopic morphometric explorations of the liver were carry out in groups of 5 each young, adult and old female Wistar rats. In addition, livers were studied 1, 5, 10, 20 days after 2/3 hepatectomy in old rats. Characteristic age-dependent change: Decrease of the surface density of total endoplasmic reticulums between 1 and 12--27 months of age. After the partial hepatectomy the regenerated old liver \"shows a certain\" rejuvenation. The results suggest the validity of the theory of accumulation of somatic mutations during aging.", "contents": "Age-dependent changes of the protein synthetic machinery of liver cell cytoplasm as revealed by electron microscopic morphometry. Complete electron microscopic morphometric explorations of the liver were carry out in groups of 5 each young, adult and old female Wistar rats. In addition, livers were studied 1, 5, 10, 20 days after 2/3 hepatectomy in old rats. Characteristic age-dependent change: Decrease of the surface density of total endoplasmic reticulums between 1 and 12--27 months of age. After the partial hepatectomy the regenerated old liver \"shows a certain\" rejuvenation. The results suggest the validity of the theory of accumulation of somatic mutations during aging."}
{"id": "PMID:22258", "title": "[Age-dependent metabolism and polymerisation of collagen (author's transl)].", "content": "Investigations of collagen metabolism on the one side and of crosslinking of fibres on the other side speak for the assumption that the decrease of synthesis of collagen correlates with an increase of its crosslinking. This process can be seen in the skin of aging rats. The increase of steady crosslinks bonds represents a regulation to elongate the life-span of fibres, that means a compensation for the decreased production of new collagen.", "contents": "[Age-dependent metabolism and polymerisation of collagen (author's transl)]. Investigations of collagen metabolism on the one side and of crosslinking of fibres on the other side speak for the assumption that the decrease of synthesis of collagen correlates with an increase of its crosslinking. This process can be seen in the skin of aging rats. The increase of steady crosslinks bonds represents a regulation to elongate the life-span of fibres, that means a compensation for the decreased production of new collagen."}
{"id": "PMID:22259", "title": "[Degenerative changes in the central region of aging human rib cartilage, as influenced by growing cross section diameter (author's transl)].", "content": "In the centre of aged human rib cartilage, a yellowing degenerative zone is seen, while in a circular peripheral region the tissue remains unchanged. The cartilage of the 12th rib shows decrease in diameter towards its free end. It therefore was used as a model to find out wether there is a critical diameter of the diffusion stretch leading to a degeneration of the centre. This stretch was to be compared with the diameter of the peripheral circular zone. Cartilage of the second rib was used for comparison. The length of the free end showing no degeneration was 2,5- to 4 mm. Its radius was longer than the diameter of the circular zone in the middle part of the 12th rib cartilage, but this was not found in the second rib cartilage nor at the base of the 12th rib cartilage. The difference between the cartilage of differing individuals was more striking than the difference found between all cross sections of the second and 12th rib cartilage. The length of the diffusion stretch is thought to be an accessorial cause of aging besides the age changes of the cells and intercellular matrix, but not the only cause.", "contents": "[Degenerative changes in the central region of aging human rib cartilage, as influenced by growing cross section diameter (author's transl)]. In the centre of aged human rib cartilage, a yellowing degenerative zone is seen, while in a circular peripheral region the tissue remains unchanged. The cartilage of the 12th rib shows decrease in diameter towards its free end. It therefore was used as a model to find out wether there is a critical diameter of the diffusion stretch leading to a degeneration of the centre. This stretch was to be compared with the diameter of the peripheral circular zone. Cartilage of the second rib was used for comparison. The length of the free end showing no degeneration was 2,5- to 4 mm. Its radius was longer than the diameter of the circular zone in the middle part of the 12th rib cartilage, but this was not found in the second rib cartilage nor at the base of the 12th rib cartilage. The difference between the cartilage of differing individuals was more striking than the difference found between all cross sections of the second and 12th rib cartilage. The length of the diffusion stretch is thought to be an accessorial cause of aging besides the age changes of the cells and intercellular matrix, but not the only cause."}
{"id": "PMID:22272", "title": "Acute hypocapneic hypokalemia: an latrogenic anesthetic complication.", "content": "Hyperventilation of patients during surgical anesthesia is a common practice in the United States. The results obtained in the present study re-emphasize serum potassium concentration is directly proportional to arterial carbon dioxide tension, and that for every 10 torr decrease in PaCO2 there is a concomitant 0.5 mEq/L decrease in potassium. Therefore sudden and significant levels of hypokalemia may occur during the course of a general anesthetic, and since hypokalemia is known to be capable of producing serious cardiac arrhythmias, hyperventilation should be avoided during surgical anesthesia, particularly in patients on drugs which produce electrophysiologic changes similar to those resulting from hypokalemia.", "contents": "Acute hypocapneic hypokalemia: an latrogenic anesthetic complication. Hyperventilation of patients during surgical anesthesia is a common practice in the United States. The results obtained in the present study re-emphasize serum potassium concentration is directly proportional to arterial carbon dioxide tension, and that for every 10 torr decrease in PaCO2 there is a concomitant 0.5 mEq/L decrease in potassium. Therefore sudden and significant levels of hypokalemia may occur during the course of a general anesthetic, and since hypokalemia is known to be capable of producing serious cardiac arrhythmias, hyperventilation should be avoided during surgical anesthesia, particularly in patients on drugs which produce electrophysiologic changes similar to those resulting from hypokalemia."}
{"id": "PMID:22276", "title": "[Early mortality after ingestion of caustic substances].", "content": "The authors define the management of a patient following emergency admission for the ingestion of a caustic liquid: immediate assessment by fibroscope oesophagoscopy; avoidance of all corticosteroid therapy and of the insertion of a gastric tube; parenteral alimentation. The frequency of early deaths has considerably decreased since the applications of this method, either as a result of shock or of the inhalation of caustic liquid.", "contents": "[Early mortality after ingestion of caustic substances]. The authors define the management of a patient following emergency admission for the ingestion of a caustic liquid: immediate assessment by fibroscope oesophagoscopy; avoidance of all corticosteroid therapy and of the insertion of a gastric tube; parenteral alimentation. The frequency of early deaths has considerably decreased since the applications of this method, either as a result of shock or of the inhalation of caustic liquid."}
{"id": "PMID:22273", "title": "Cerebral surface pH changes during asphyxia, hypotension, and circulatory arrest in the dog.", "content": "A technic is described for the measurement of cerebral surface pH in acute experiments in anesthetized dogs. During asphyxia and circulatory arrest, cerebral surface pH fell promptly and more profoundly than arterial blood or muscle surface pH; during hypovolemic hypotension (30 to 50 torr) cerebral surface pH declined later and less than muscle surface pH. The cerebral surface pH reflects the pH of the cortical interstitial fluid. Since the blood brain barrier is effectively impermeable to lactate, the changes recorded in the cerebral surface pH are a useful index of cortical intracellular metabolism.", "contents": "Cerebral surface pH changes during asphyxia, hypotension, and circulatory arrest in the dog. A technic is described for the measurement of cerebral surface pH in acute experiments in anesthetized dogs. During asphyxia and circulatory arrest, cerebral surface pH fell promptly and more profoundly than arterial blood or muscle surface pH; during hypovolemic hypotension (30 to 50 torr) cerebral surface pH declined later and less than muscle surface pH. The cerebral surface pH reflects the pH of the cortical interstitial fluid. Since the blood brain barrier is effectively impermeable to lactate, the changes recorded in the cerebral surface pH are a useful index of cortical intracellular metabolism."}
{"id": "PMID:22277", "title": "[Anesthesia for esophageal surgery].", "content": "At the present time, it is rarely necessary to operate after a digestive perforation complicating the ingestion of a caustic fluid. By contrast, cancer surgery progresses. Anaesthesia requires protection with a high degree of analgesia and curarisation. The use of a Carlens tube during oesophagectomy via a thoracic approach facilitates the surgeon's task. Compensation for blood and water losses should be generous. Insertion of a gastric tube through the plasty makes it possible to avoid gastrostomy. Finally, postoperative artificial ventilation is necessary in these individuals who often suffer from some form of respiratory pathology.", "contents": "[Anesthesia for esophageal surgery]. At the present time, it is rarely necessary to operate after a digestive perforation complicating the ingestion of a caustic fluid. By contrast, cancer surgery progresses. Anaesthesia requires protection with a high degree of analgesia and curarisation. The use of a Carlens tube during oesophagectomy via a thoracic approach facilitates the surgeon's task. Compensation for blood and water losses should be generous. Insertion of a gastric tube through the plasty makes it possible to avoid gastrostomy. Finally, postoperative artificial ventilation is necessary in these individuals who often suffer from some form of respiratory pathology."}
{"id": "PMID:22278", "title": "[Surgical treatment of caustic esophagogastric stenosis in the chronic phase].", "content": "The authors report the results of 26 oesophagoplasties carried out using the descending colon for oesophageal stenosis as a result of a caustic lesion. Superior: in 5 cases the anastomosis being made to the pharynx. Inferior: 8 associated gastric lesions being treated either by resection or by short circuit. The remaining oesophagus was removed in two cases. There were two postoperative deaths. In all the remaining patients a satisfactory functional result was obtained.", "contents": "[Surgical treatment of caustic esophagogastric stenosis in the chronic phase]. The authors report the results of 26 oesophagoplasties carried out using the descending colon for oesophageal stenosis as a result of a caustic lesion. Superior: in 5 cases the anastomosis being made to the pharynx. Inferior: 8 associated gastric lesions being treated either by resection or by short circuit. The remaining oesophagus was removed in two cases. There were two postoperative deaths. In all the remaining patients a satisfactory functional result was obtained."}
{"id": "PMID:22279", "title": "[Intensive care and diet in cases of caustic esophageal stenosis after the first eight days].", "content": "On the basis of 12 cases of caustic burns of the oesophagus, the authors describe the technique of alimentation, once the acute phase of the first eight days has passed. From the 8th to the 15th days, calories and provided parenterally. An upper GI series is carried out on the 15th day: if the stomach is healthy, the authors fashion an alimentation gastrostomy, if the stomach is damaged, they carry out gastrectomy with alimentation gastrostomy or jejunostomy. In all cases, continuity is re-established by coloplasty two months later.", "contents": "[Intensive care and diet in cases of caustic esophageal stenosis after the first eight days]. On the basis of 12 cases of caustic burns of the oesophagus, the authors describe the technique of alimentation, once the acute phase of the first eight days has passed. From the 8th to the 15th days, calories and provided parenterally. An upper GI series is carried out on the 15th day: if the stomach is healthy, the authors fashion an alimentation gastrostomy, if the stomach is damaged, they carry out gastrectomy with alimentation gastrostomy or jejunostomy. In all cases, continuity is re-established by coloplasty two months later."}
{"id": "PMID:22280", "title": "[Caustic lesions of the esophagus in the child].", "content": "On the basis of a study involving 21 children treated over a 10 year period, the authors describe a method for the management of a child following the ingestion of a caustic fluid: emergency oesophagoscopy to determine the extent and nature on the lesions, in severe forms, alimentation gastrostomy, which would seem to be preferable to parenteral alimentation, is carried out, on the 21st day, a new endoscopic and radiological assessment, permitting distinction between those cases which are cured and those progressing to stenosis. In this latter group, the choice is made between dilatations and oesophagoplasty on the basis on the lesions present and the development of complications during dilatation.", "contents": "[Caustic lesions of the esophagus in the child]. On the basis of a study involving 21 children treated over a 10 year period, the authors describe a method for the management of a child following the ingestion of a caustic fluid: emergency oesophagoscopy to determine the extent and nature on the lesions, in severe forms, alimentation gastrostomy, which would seem to be preferable to parenteral alimentation, is carried out, on the 21st day, a new endoscopic and radiological assessment, permitting distinction between those cases which are cured and those progressing to stenosis. In this latter group, the choice is made between dilatations and oesophagoplasty on the basis on the lesions present and the development of complications during dilatation."}
{"id": "PMID:22281", "title": "[Perforations of the cervical esophagus in attempted tracheal intubation. A report of 12 cases].", "content": "The authors underline the factors favouring perforation of the oesophagus during intubation in the light of 12 personal cases: difficulty in intubation, use of an introducer, inexperienced operator. Such a perforation may result in mediastinitis and should be treated early with massive polyvalent antibiotics and a surgical suture left at rest for approximately one week.", "contents": "[Perforations of the cervical esophagus in attempted tracheal intubation. A report of 12 cases]. The authors underline the factors favouring perforation of the oesophagus during intubation in the light of 12 personal cases: difficulty in intubation, use of an introducer, inexperienced operator. Such a perforation may result in mediastinitis and should be treated early with massive polyvalent antibiotics and a surgical suture left at rest for approximately one week."}
{"id": "PMID:22282", "title": "[Pharyngolaryngeal fistula and hypopharyngeal perforation resulting from difficult tracheal intubation].", "content": "The authors report a case of lesions of the pharyngo-oesophagolaryngeal junction following difficult intubation. On the basis of the small number of cases published in recent years, they attempt to determine those factors which may permit early diagnosis before the development of complications in order that any medical or surgical therapeutic measures applied may be fully effective.", "contents": "[Pharyngolaryngeal fistula and hypopharyngeal perforation resulting from difficult tracheal intubation]. The authors report a case of lesions of the pharyngo-oesophagolaryngeal junction following difficult intubation. On the basis of the small number of cases published in recent years, they attempt to determine those factors which may permit early diagnosis before the development of complications in order that any medical or surgical therapeutic measures applied may be fully effective."}
{"id": "PMID:22283", "title": "[Surgery for carcinoma of the esophagus. Methods and techniques].", "content": "Given the poor prognosis in carcinoma of the oesophagus, and with the aid of advances in anaesthesia and postoperative care, surgery has progressively evolved towards wider excision and a reduction in the number of operative stages. Partial oesophagectomy, with gastrolysis and gastro-oesophageal anastomosis, via a left thoracotomy, is favoured by large number of authors. However, it involves a certain number of disadvantages: by definition a limited excision, unsuitable for carcinomas in the cervical region and a marked risk of postoperative gastro-oesophageal reflux. Total oesophagectomy offers a hope of better results from an oncological standpoint, the more so since excision may be extended superiorly (laryngectomy) or inferiorly (total gastrectomy with lymph node excision). Continuity is re-established using a colonic transplant. The operation may be performed in two stages, though a single stage procedure with two teams would appear to be preferable, overall mortality and morbidity being reduced. Finally, colonic oesophagoplasty may be used alone, as a simply palliative measure, without associated tumour excision. By short-circuiting the oesophageal stenosis, it permits continued alimentation per os and the patient's period of survival is more comfortable.", "contents": "[Surgery for carcinoma of the esophagus. Methods and techniques]. Given the poor prognosis in carcinoma of the oesophagus, and with the aid of advances in anaesthesia and postoperative care, surgery has progressively evolved towards wider excision and a reduction in the number of operative stages. Partial oesophagectomy, with gastrolysis and gastro-oesophageal anastomosis, via a left thoracotomy, is favoured by large number of authors. However, it involves a certain number of disadvantages: by definition a limited excision, unsuitable for carcinomas in the cervical region and a marked risk of postoperative gastro-oesophageal reflux. Total oesophagectomy offers a hope of better results from an oncological standpoint, the more so since excision may be extended superiorly (laryngectomy) or inferiorly (total gastrectomy with lymph node excision). Continuity is re-established using a colonic transplant. The operation may be performed in two stages, though a single stage procedure with two teams would appear to be preferable, overall mortality and morbidity being reduced. Finally, colonic oesophagoplasty may be used alone, as a simply palliative measure, without associated tumour excision. By short-circuiting the oesophageal stenosis, it permits continued alimentation per os and the patient's period of survival is more comfortable."}
{"id": "PMID:22284", "title": "[Postoperative complications in esophageal surgery].", "content": "Apart from certain complications which may follow any surgical procedure, the authors sought to emphasise in particular the problems posed by fistulae occurring after oesophageal surgery. They draw a clear distinction between cervical fistulae which, draining adequately, do not affect the vital prognosis, merely prolonging the period of hospitalisation, and intrathoracic or sub-diaphragmatic fistulae, with a grave prognosis and which pose delicate problems of re-operation, drainage and intensive care. They feel that the possibility of prevention of these digestive fistulae must be stressed, combining the most meticulous surgical technique with appropriate pre- and postoperative care.", "contents": "[Postoperative complications in esophageal surgery]. Apart from certain complications which may follow any surgical procedure, the authors sought to emphasise in particular the problems posed by fistulae occurring after oesophageal surgery. They draw a clear distinction between cervical fistulae which, draining adequately, do not affect the vital prognosis, merely prolonging the period of hospitalisation, and intrathoracic or sub-diaphragmatic fistulae, with a grave prognosis and which pose delicate problems of re-operation, drainage and intensive care. They feel that the possibility of prevention of these digestive fistulae must be stressed, combining the most meticulous surgical technique with appropriate pre- and postoperative care."}
{"id": "PMID:22285", "title": "[Preoperative assessment: value and limitations in the preparation for surgery of esophageal or cardia carcinoma].", "content": "Pre-operative assessment of a patient suffering from a carcinoma of the oesophagus demonstrates numerous pathological features and marked malnutrition. The authors give details of their method of nutritional preparation: operation is scheduled only when the patients are restored to a state of anabolism, i.e. when daily potassium balance is greater than 40 mEq and daily nitrogen balance exceeds 4 g. Carolies are provided either intravenously or via a gastric tube. Alimentation consists on average of 2,000 to 2,6000 calories as carbohydrate and lipids and 12 to 14 g of nitrogen. This preparation lasts on average for one week. It is associated with a reduction in mortality and the number of postoperative complications.", "contents": "[Preoperative assessment: value and limitations in the preparation for surgery of esophageal or cardia carcinoma]. Pre-operative assessment of a patient suffering from a carcinoma of the oesophagus demonstrates numerous pathological features and marked malnutrition. The authors give details of their method of nutritional preparation: operation is scheduled only when the patients are restored to a state of anabolism, i.e. when daily potassium balance is greater than 40 mEq and daily nitrogen balance exceeds 4 g. Carolies are provided either intravenously or via a gastric tube. Alimentation consists on average of 2,000 to 2,6000 calories as carbohydrate and lipids and 12 to 14 g of nitrogen. This preparation lasts on average for one week. It is associated with a reduction in mortality and the number of postoperative complications."}
{"id": "PMID:22286", "title": "[Practical problems and results of parenteral alimentation in 60 patients undergoing surgery for neoplasms of the esophagus].", "content": "Sixty patients suffering from a neoplasm of the oesophagus underwent surgery. All received parenteral alimentation in an intensive care unit and its value was studied, in particular in the immediate postoperative period. Describing the technique used, together with the qualitative and quantitative nature of the products employed, the authors analyse the results obtained and in particular the effectiveness of treatment from the standpoint of protein balance and of body weight stability in these patients.", "contents": "[Practical problems and results of parenteral alimentation in 60 patients undergoing surgery for neoplasms of the esophagus]. Sixty patients suffering from a neoplasm of the oesophagus underwent surgery. All received parenteral alimentation in an intensive care unit and its value was studied, in particular in the immediate postoperative period. Describing the technique used, together with the qualitative and quantitative nature of the products employed, the authors analyse the results obtained and in particular the effectiveness of treatment from the standpoint of protein balance and of body weight stability in these patients."}
{"id": "PMID:22287", "title": "[Tracheo-bronchial intubation for surgery of the esophagus via a thoracic approach].", "content": "Tracheo-bronchial intubation using a double-lumen Carlens tube provides the surgeon with a mediastinal operating field free of any obstruction by the lung and provides greater surgical ease than that of an assistant retracting a constantly invasive lung with tracheal intubation. This anaesthetic technique involving the ventilation of only one lung during the endothoracic period of the surgical procedure has not been used routinely for extra-pulmonary surgery since the shunt which is created leads to a fear of dangerous hypoxia. The aim of this study involving 30 patients is to demonstrate that the blood oxygen saturation obtained by the careful ventilation of a single lung, that of the side on which the patient is lying, is perfectly acceptable and comparable with the preoperative oxygen saturation of the subject at rest. This is obtained at the price of an increase in insufflation pressures of the order of 100 percent. Re-expansion of the collapsed lung without visual confirmation after careful endobronchial aspiration makes it possible to prevent the development of areas of micro-atelectasia and to ensure the absence of any pulmonary postoperative complications.", "contents": "[Tracheo-bronchial intubation for surgery of the esophagus via a thoracic approach]. Tracheo-bronchial intubation using a double-lumen Carlens tube provides the surgeon with a mediastinal operating field free of any obstruction by the lung and provides greater surgical ease than that of an assistant retracting a constantly invasive lung with tracheal intubation. This anaesthetic technique involving the ventilation of only one lung during the endothoracic period of the surgical procedure has not been used routinely for extra-pulmonary surgery since the shunt which is created leads to a fear of dangerous hypoxia. The aim of this study involving 30 patients is to demonstrate that the blood oxygen saturation obtained by the careful ventilation of a single lung, that of the side on which the patient is lying, is perfectly acceptable and comparable with the preoperative oxygen saturation of the subject at rest. This is obtained at the price of an increase in insufflation pressures of the order of 100 percent. Re-expansion of the collapsed lung without visual confirmation after careful endobronchial aspiration makes it possible to prevent the development of areas of micro-atelectasia and to ensure the absence of any pulmonary postoperative complications."}
{"id": "PMID:22288", "title": "[The influence of preoperative irradiation on postoperative complications in surgical treatment of carcinoma of the esophagus].", "content": "Over a 15 year period, the authors operated upon 650 patients suffering from carcinoma of the oesophagus. Amongst them, 185 underwent pre-operative irradiation. The latter appears to increase the percentage in whom excision was possible. By contrast, the occurence rate of postoperative complications is essentially the same in both groups of patients apart from chylothorax which was more common in the irradiated subjects.", "contents": "[The influence of preoperative irradiation on postoperative complications in surgical treatment of carcinoma of the esophagus]. Over a 15 year period, the authors operated upon 650 patients suffering from carcinoma of the oesophagus. Amongst them, 185 underwent pre-operative irradiation. The latter appears to increase the percentage in whom excision was possible. By contrast, the occurence rate of postoperative complications is essentially the same in both groups of patients apart from chylothorax which was more common in the irradiated subjects."}
{"id": "PMID:22289", "title": "[The value of early routine radiological examination following esophagectomy for carcinoma of the lower third of the esophagus].", "content": "An early upper gastrointestinal series may be carried out on a routine basis after recovery of the postoperative ileus and makes it possible to confirm the good quality of the anastomoses or, by contrast, reveal a benign fistula. Under some circumstances, it may be carried out very early following the development of postoperative complications: pain, fever, respiratory, circulatory and renal insufficiency or in the presence of abnormal discharge from the drains. It then shows whether this complication is due to an oesophagomediastinal or pleural fistula.", "contents": "[The value of early routine radiological examination following esophagectomy for carcinoma of the lower third of the esophagus]. An early upper gastrointestinal series may be carried out on a routine basis after recovery of the postoperative ileus and makes it possible to confirm the good quality of the anastomoses or, by contrast, reveal a benign fistula. Under some circumstances, it may be carried out very early following the development of postoperative complications: pain, fever, respiratory, circulatory and renal insufficiency or in the presence of abnormal discharge from the drains. It then shows whether this complication is due to an oesophagomediastinal or pleural fistula."}
{"id": "PMID:22290", "title": "[Postoperative pulmonary complications following surgery for carcinoma of the esophagus].", "content": "Pulmonary complications frequently occur during the postoperative period following surgery for neoplasms of the oesophagus. The aetiology varies according to the time of their onset but the clinical signs and treatment are essentially the same. The problems encountered and related either to anaesthesia, to the surgical approach to the position of the patient. It is after the third day that complication develop related at one and the same to the past history, classical in such patients, (tobacco, chronic bronchitis, alcoholism) and the ectopic position of an abdominal viscus.", "contents": "[Postoperative pulmonary complications following surgery for carcinoma of the esophagus]. Pulmonary complications frequently occur during the postoperative period following surgery for neoplasms of the oesophagus. The aetiology varies according to the time of their onset but the clinical signs and treatment are essentially the same. The problems encountered and related either to anaesthesia, to the surgical approach to the position of the patient. It is after the third day that complication develop related at one and the same to the past history, classical in such patients, (tobacco, chronic bronchitis, alcoholism) and the ectopic position of an abdominal viscus."}
{"id": "PMID:22291", "title": "[Pulmonary complications of esophagectomy for carcinoma of the middle third of the esophagus].", "content": "The authors studied 20 patients undergoing operation for a carcinoma of the middle third of the oesophagus during the period January 1972 to April 1975. Postoperative pulmonary complications are extremely common in such patients. All the patients had pulmonary function study results which were compatible with this type of surgery. All underwent resection with oesophagogastric anastomosis via a left thoracophrenolaparotomy. Of the 20 patients, 14 suffered from one or more episodes of acute respiratory insufficiency, some related to pneumonia. On the basis of various associated clinical, radiological, biological, evolutive and histopathological criteria, five types of pulmonary complication were distinguished: 1-Shock lung; 2-Infective pneumonia; 3-Traumatic pulmonary disease; 4-Acute cor pulmonale; 5-Lung disease of undetermined origin. Twelve patients died as a result of pulmonary complications, 11 early (before the 16th day). One patient only died as a result of rupture of the oesophagogastric anastomosis.", "contents": "[Pulmonary complications of esophagectomy for carcinoma of the middle third of the esophagus]. The authors studied 20 patients undergoing operation for a carcinoma of the middle third of the oesophagus during the period January 1972 to April 1975. Postoperative pulmonary complications are extremely common in such patients. All the patients had pulmonary function study results which were compatible with this type of surgery. All underwent resection with oesophagogastric anastomosis via a left thoracophrenolaparotomy. Of the 20 patients, 14 suffered from one or more episodes of acute respiratory insufficiency, some related to pneumonia. On the basis of various associated clinical, radiological, biological, evolutive and histopathological criteria, five types of pulmonary complication were distinguished: 1-Shock lung; 2-Infective pneumonia; 3-Traumatic pulmonary disease; 4-Acute cor pulmonale; 5-Lung disease of undetermined origin. Twelve patients died as a result of pulmonary complications, 11 early (before the 16th day). One patient only died as a result of rupture of the oesophagogastric anastomosis."}
{"id": "PMID:22294", "title": "[Peroperative sinus arrest in a patient with sick sinus syndrome (apropos of a case)].", "content": "A sinus arrest occured during a surgical intervention in a patient suffering from a sinus nodal dysfunction. The Fentanyl acetate used as an analg\u00e9sic, seems to have played an important role in the genesis of the accident, depressing sinusal and junctional automatisms. Though unusual, this complication leads to a further investigation in preoperative period for a possible sinus nodal dysfunction in order to anticipate an extreme preoperative bradycardia (sino atrial block) treated with intravenous administration of isoprenaline. Intraveinous atropine test is a simple preoperative technique of research in front all unexplained sinus bradycardia.", "contents": "[Peroperative sinus arrest in a patient with sick sinus syndrome (apropos of a case)]. A sinus arrest occured during a surgical intervention in a patient suffering from a sinus nodal dysfunction. The Fentanyl acetate used as an analg\u00e9sic, seems to have played an important role in the genesis of the accident, depressing sinusal and junctional automatisms. Though unusual, this complication leads to a further investigation in preoperative period for a possible sinus nodal dysfunction in order to anticipate an extreme preoperative bradycardia (sino atrial block) treated with intravenous administration of isoprenaline. Intraveinous atropine test is a simple preoperative technique of research in front all unexplained sinus bradycardia."}
{"id": "PMID:22295", "title": "[Trial droperidol premedication in infants and children].", "content": "Droperidol premedication for children (0.3 to 0.5 mg/kg) was compared with pentobarbital and Dolosal--promethazine). Results are analyzed using criteria proposed by Burken and Nisbet. Droperidol compared very favourably with the order drugs. However a decrease in efficacy was noted with infants and neuw-born children, even with higher doses. The possible incidence it hypertonic seizures renders this drug unsuitable for ambulatory surgery.", "contents": "[Trial droperidol premedication in infants and children]. Droperidol premedication for children (0.3 to 0.5 mg/kg) was compared with pentobarbital and Dolosal--promethazine). Results are analyzed using criteria proposed by Burken and Nisbet. Droperidol compared very favourably with the order drugs. However a decrease in efficacy was noted with infants and neuw-born children, even with higher doses. The possible incidence it hypertonic seizures renders this drug unsuitable for ambulatory surgery."}
{"id": "PMID:22297", "title": "[Prevention by pindolol of electrocardiographic changes during bronchoscopy performed under local and general anesthesia].", "content": "Sixty patients were studied with respect to ECG modifications during bronchoscopy under local or general anesthesia, using dynamic electrocardiography. The increase in heart rate and incidence of extra-systoles were greater under local than general anesthesia. When pindolol, a beta-blocker with practically no bronchospastic effect was administered before the procedure, there was a significant decrease in the incidence of tachycardia and extra-systoles. This drug appears to be useful before bronchoscopy.", "contents": "[Prevention by pindolol of electrocardiographic changes during bronchoscopy performed under local and general anesthesia]. Sixty patients were studied with respect to ECG modifications during bronchoscopy under local or general anesthesia, using dynamic electrocardiography. The increase in heart rate and incidence of extra-systoles were greater under local than general anesthesia. When pindolol, a beta-blocker with practically no bronchospastic effect was administered before the procedure, there was a significant decrease in the incidence of tachycardia and extra-systoles. This drug appears to be useful before bronchoscopy."}
{"id": "PMID:22298", "title": "[Electric burns in the operating room. Apropos of 4 cases].", "content": "Four cases of patients suffering from peroperative skin burns at electrocardioscope electrode sites are reported. They were the result of incorrect function of the cutting diathermy, (error of internal or external connection). Use of the electrocardioscope with a \"floating input\" protects the patient against this type of electrical accident.", "contents": "[Electric burns in the operating room. Apropos of 4 cases]. Four cases of patients suffering from peroperative skin burns at electrocardioscope electrode sites are reported. They were the result of incorrect function of the cutting diathermy, (error of internal or external connection). Use of the electrocardioscope with a \"floating input\" protects the patient against this type of electrical accident."}
{"id": "PMID:22300", "title": "[A case of survival after 65 hours of immersion in the Mediterranean].", "content": "Survical time of a man immerged in sea water at a mean temperature of 20 degrees C was 65 hours. This remarkable tolerance of a professional diver to hypothermia is attributed to his adapted clothing and safety equipment, and to favourable atmospheric conditions. On the light of this accidental immersion, one must reconsider out of date concepts concerning sea rescue with respect to water temperature, clothing equipment of the ship-wrecked, meterological conditions and circonstances of accident.", "contents": "[A case of survival after 65 hours of immersion in the Mediterranean]. Survical time of a man immerged in sea water at a mean temperature of 20 degrees C was 65 hours. This remarkable tolerance of a professional diver to hypothermia is attributed to his adapted clothing and safety equipment, and to favourable atmospheric conditions. On the light of this accidental immersion, one must reconsider out of date concepts concerning sea rescue with respect to water temperature, clothing equipment of the ship-wrecked, meterological conditions and circonstances of accident."}
{"id": "PMID:22301", "title": "[Comparative study of nitrogen sparing during parenteral feeding as a function of carbohydrate intake].", "content": "The nitrogen balance of two groups of patients, A and B, was studied during the first four post-operative days. Groups A (31) received a daily intake of one liter of Totamine concentr\u00e9e glucidique with glucose 10 p. 100 1,5 liter. Groups B received Totamine concentr\u00e9e glucidique with glucose 30 p. 100 1,5 liter. There was no statistically significant difference in nitrogen balance between both groups. On the other hand, the cumulative nitrogen balance was positive for both groups for the first four post-operative days.", "contents": "[Comparative study of nitrogen sparing during parenteral feeding as a function of carbohydrate intake]. The nitrogen balance of two groups of patients, A and B, was studied during the first four post-operative days. Groups A (31) received a daily intake of one liter of Totamine concentr\u00e9e glucidique with glucose 10 p. 100 1,5 liter. Groups B received Totamine concentr\u00e9e glucidique with glucose 30 p. 100 1,5 liter. There was no statistically significant difference in nitrogen balance between both groups. On the other hand, the cumulative nitrogen balance was positive for both groups for the first four post-operative days."}
{"id": "PMID:22302", "title": "[26 cases of tracheal stenosis after prolonged intubation or tracheotomy. Personal retrospective study].", "content": "A retrospective study over a period of 10 years, involving different hospital departments, revealed a total of 26 patients with post-intubation and/or post-prolonged tracheotomy stenosis which required surgical treatment. Predisposing factors included poor general condition, infection, iatrogenic factors related to intensive therapy (respiration, inadequate nursing) and the duration. Stenosis were situated from the sub-glottis to the carina. After surgical treatment, there were ten cases of restenosis, two multiple, and one inflammatory granuloma. Intubation may be life-saving, but must be performed by an individual competent in the procedure, under strictly aseptic conditions, and using non-traumatic disposable material. The patient should undergo thorough ENT examination at the time of extubation, repeated one month and six months later.", "contents": "[26 cases of tracheal stenosis after prolonged intubation or tracheotomy. Personal retrospective study]. A retrospective study over a period of 10 years, involving different hospital departments, revealed a total of 26 patients with post-intubation and/or post-prolonged tracheotomy stenosis which required surgical treatment. Predisposing factors included poor general condition, infection, iatrogenic factors related to intensive therapy (respiration, inadequate nursing) and the duration. Stenosis were situated from the sub-glottis to the carina. After surgical treatment, there were ten cases of restenosis, two multiple, and one inflammatory granuloma. Intubation may be life-saving, but must be performed by an individual competent in the procedure, under strictly aseptic conditions, and using non-traumatic disposable material. The patient should undergo thorough ENT examination at the time of extubation, repeated one month and six months later."}
{"id": "PMID:22304", "title": "H2-Histamine receptor blocking agents in the Zollinger-Ellison syndrome. Experience in seven cases and implications for long-term therapy.", "content": "H2-Histamine receptor blocking agents metiamide and cimetidine were assessed in seven patients with Zollinger-Ellison syndrome (serum gastrin greater than 300 microgram/ml, basal acid output greater than 15 meq/h, ratio of basal acid output to maximal acid output greater than 0.5). Intravenous or oral administration of the drugs lowered acid secretion by at least 70% in all cases. Subsequent treatment of six patients for 3 to 15 months (oral therapy) and one patient for 1 month (intravenous therapy) showed that the drugs abolished symptoms in all seven, abolished diarrhea in five, allowed ulcer healing in six, and were well tolerated without adverse effects in seven. No patient failed to respond to the drug, although one died from tumor progression and two required total gastrectomy for complex reasons. The results indicate that patients with Zollinger-Ellison syndrome can be managed medically and, in light of current mortality trends, gain little from the extra risks attending total gastrectomy.", "contents": "H2-Histamine receptor blocking agents in the Zollinger-Ellison syndrome. Experience in seven cases and implications for long-term therapy. H2-Histamine receptor blocking agents metiamide and cimetidine were assessed in seven patients with Zollinger-Ellison syndrome (serum gastrin greater than 300 microgram/ml, basal acid output greater than 15 meq/h, ratio of basal acid output to maximal acid output greater than 0.5). Intravenous or oral administration of the drugs lowered acid secretion by at least 70% in all cases. Subsequent treatment of six patients for 3 to 15 months (oral therapy) and one patient for 1 month (intravenous therapy) showed that the drugs abolished symptoms in all seven, abolished diarrhea in five, allowed ulcer healing in six, and were well tolerated without adverse effects in seven. No patient failed to respond to the drug, although one died from tumor progression and two required total gastrectomy for complex reasons. The results indicate that patients with Zollinger-Ellison syndrome can be managed medically and, in light of current mortality trends, gain little from the extra risks attending total gastrectomy."}
{"id": "PMID:22305", "title": "Protective effect of cimetidine on aspirin-induced gastric mucosal damage.", "content": "Aspirin alters the gastric mucosal barrier as measured by ionic flux and potential difference. The effect of cimetidine on aspirin-induced alterations in gastric mucosa was studied in five normal male volunteers. Aspirin effects were studied with and without previous treatment with cimetidine. Mean (+/- SEM) basal potential difference was -48 +/- 1 mV. After 600 mg of aspirin in 1 dl of isotonic saline, potential difference decreased in 10 min to -39 +/- 1 mV (P less than 0.001) and returned to baseline within 60 min. Control biopsies showed 2% damaged mucosal cells compared with 20% damaged at the time of maximal drop in potential difference (P less than 0.001) after aspirin. Recovery to 9% damage occurred by 60 min. In subjects pretreated with 300 mg cimetidine, potential difference rose during 1 h to -62 +/- 1 mV (P less than 0.001). After aspirin potential difference fell to -48 +/- 1 mV compared with -39 +/- 1 mV with aspirin alone (P less than 0.01) and returned to -62 +/- 1 mV at 60 min. The cimetidine-treated group showed 4% mucosal damage at the peak potential difference fall after aspirin, significantly less (P less than 0.02) than in the untreated subjects.", "contents": "Protective effect of cimetidine on aspirin-induced gastric mucosal damage. Aspirin alters the gastric mucosal barrier as measured by ionic flux and potential difference. The effect of cimetidine on aspirin-induced alterations in gastric mucosa was studied in five normal male volunteers. Aspirin effects were studied with and without previous treatment with cimetidine. Mean (+/- SEM) basal potential difference was -48 +/- 1 mV. After 600 mg of aspirin in 1 dl of isotonic saline, potential difference decreased in 10 min to -39 +/- 1 mV (P less than 0.001) and returned to baseline within 60 min. Control biopsies showed 2% damaged mucosal cells compared with 20% damaged at the time of maximal drop in potential difference (P less than 0.001) after aspirin. Recovery to 9% damage occurred by 60 min. In subjects pretreated with 300 mg cimetidine, potential difference rose during 1 h to -62 +/- 1 mV (P less than 0.001). After aspirin potential difference fell to -48 +/- 1 mV compared with -39 +/- 1 mV with aspirin alone (P less than 0.01) and returned to -62 +/- 1 mV at 60 min. The cimetidine-treated group showed 4% mucosal damage at the peak potential difference fall after aspirin, significantly less (P less than 0.02) than in the untreated subjects."}
{"id": "PMID:22306", "title": "Sj\u00f6gren-type syndrome after allogeneic bone-marrow transplantation.", "content": "Four patients, treated for hematologic disorders with bone-marrow transplants from HLA-identical siblings, spontaneously complained of dry eyes 8 to 12 months after transplantation. Four allograft recipients and two recipients of autologous bone-marrow transplants were evaluated for xerophthalmia and xerostomia. Three allogeneic marrow recipients had evidence of keratoconjunctivitis sicca, and two had decreased parotid gland function. All four allograft recipients had minor salivary gland histopathology identical to that of Sj\u00f6gren's syndrome. The severity of symptoms and histologic lesions corresponded with the severity of chronic graft-versus-host disease. In addition, one patient developed sclerodermatous skin changes, another had discoid lupus erythematosus, and two patients had laboratory evidence of cholestasis. None of the patients had autoantibodies but all had hypergammaglobulinemia. In contrast, none of the recipients of autologous bone marrow had clinical, laboratory, or histologic findings resembling Sj\u00f6gren's syndrome.", "contents": "Sj\u00f6gren-type syndrome after allogeneic bone-marrow transplantation. Four patients, treated for hematologic disorders with bone-marrow transplants from HLA-identical siblings, spontaneously complained of dry eyes 8 to 12 months after transplantation. Four allograft recipients and two recipients of autologous bone-marrow transplants were evaluated for xerophthalmia and xerostomia. Three allogeneic marrow recipients had evidence of keratoconjunctivitis sicca, and two had decreased parotid gland function. All four allograft recipients had minor salivary gland histopathology identical to that of Sj\u00f6gren's syndrome. The severity of symptoms and histologic lesions corresponded with the severity of chronic graft-versus-host disease. In addition, one patient developed sclerodermatous skin changes, another had discoid lupus erythematosus, and two patients had laboratory evidence of cholestasis. None of the patients had autoantibodies but all had hypergammaglobulinemia. In contrast, none of the recipients of autologous bone marrow had clinical, laboratory, or histologic findings resembling Sj\u00f6gren's syndrome."}
{"id": "PMID:22307", "title": "Scleroderma, Sj\u00f6gren-like syndrome, and chronic graft-versus-host disease.", "content": "A patient with acute myelogenous leukemia treated with an allogeneic bone marrow transplant developed acute graft-versus-host disease manifested by severe diarrhea, hepatitis, and a cutaneous eruption. As the graft-versus-host disease progressed to the chronic phase, the patient developed marked cutaneous sclerosis and symptoms of xerophthalmia and xerostomia. Biopsy of his indurated skin showed features of both graft-versus-host disease and scleroderma. Results of Schirmer's tests, corneal fluorescent studies, parotid flow-rate testing, and a lip biopsy were consistent with Sj\u00f6gren's syndrome. Possibly, activated lymphocytes may have a role in the pathogenesis of graft-versus-host disease, scleroderma, and Sj\u00f6gren's syndrome.", "contents": "Scleroderma, Sj\u00f6gren-like syndrome, and chronic graft-versus-host disease. A patient with acute myelogenous leukemia treated with an allogeneic bone marrow transplant developed acute graft-versus-host disease manifested by severe diarrhea, hepatitis, and a cutaneous eruption. As the graft-versus-host disease progressed to the chronic phase, the patient developed marked cutaneous sclerosis and symptoms of xerophthalmia and xerostomia. Biopsy of his indurated skin showed features of both graft-versus-host disease and scleroderma. Results of Schirmer's tests, corneal fluorescent studies, parotid flow-rate testing, and a lip biopsy were consistent with Sj\u00f6gren's syndrome. Possibly, activated lymphocytes may have a role in the pathogenesis of graft-versus-host disease, scleroderma, and Sj\u00f6gren's syndrome."}
{"id": "PMID:22310", "title": "Penicillic acid production in submerged culture.", "content": "Twenty known penicillic acid (PA)-producing Aspergillus and Penicillium cultures were grown under various conditions in shaken flasks to determine the highest yielding strains and their requirements for maximum toxin production. Abilities of the cultures to utilize eight different carbon sources in Raulin-Thom medium for mycotoxin synthesis were determined at four different incubation temperatures: 15, 20, 25, and 28 degrees C. Of the 20 cultures, P. cyclopium NRRL 1888 was superior, yielding up to 4 mg of PG per ml, with mannitol as the carbon source and 25 degrees C as the incubation temperature. Fifteen of the cultures elaborated lesser amounts of PA, whereas four strains yielded none under the test conditions. Whey from the manufacture of cottage cheese by the cultured process was also a satisfactory medium for PA production. In whey medium, yields up to 3 mg/ml were obtained with P. cyclopium NRRL 1888.", "contents": "Penicillic acid production in submerged culture. Twenty known penicillic acid (PA)-producing Aspergillus and Penicillium cultures were grown under various conditions in shaken flasks to determine the highest yielding strains and their requirements for maximum toxin production. Abilities of the cultures to utilize eight different carbon sources in Raulin-Thom medium for mycotoxin synthesis were determined at four different incubation temperatures: 15, 20, 25, and 28 degrees C. Of the 20 cultures, P. cyclopium NRRL 1888 was superior, yielding up to 4 mg of PG per ml, with mannitol as the carbon source and 25 degrees C as the incubation temperature. Fifteen of the cultures elaborated lesser amounts of PA, whereas four strains yielded none under the test conditions. Whey from the manufacture of cottage cheese by the cultured process was also a satisfactory medium for PA production. In whey medium, yields up to 3 mg/ml were obtained with P. cyclopium NRRL 1888."}
{"id": "PMID:22311", "title": "Nitrogen fixation, denitrification, and pleomorphic growth in a highly pigmented Spirillum lipoferum.", "content": "A strain of Spirillum lipoferum with intense red pigmentation was isolated from the roots of Cynodon dactylon \"Coastal.\" This isolate vigorously reduced acetylene when grown in N-free, Na-malate, semisolid agar, and it was identical to S. lipoferum strain SP7 by standard taxonomic tests. Both S. lipoferum SP7 and the C. dactylon root isolate displayed the unique features of being denitrifiers as well as N2 fixers. The N2-dependent growth curve was biphasic: cells in younger cultures showed the characteristic spiral shape and motility, but those in older cultures developed larger, nonmotile, cystlike forms. Nitrogenase activity seemed associated only with younger spiral forms. The red pigment may be a b- or c-type cytochrome. The strong red color, which this strain develops, could be used as a marker in evaluating soil inoculation experiments.", "contents": "Nitrogen fixation, denitrification, and pleomorphic growth in a highly pigmented Spirillum lipoferum. A strain of Spirillum lipoferum with intense red pigmentation was isolated from the roots of Cynodon dactylon \"Coastal.\" This isolate vigorously reduced acetylene when grown in N-free, Na-malate, semisolid agar, and it was identical to S. lipoferum strain SP7 by standard taxonomic tests. Both S. lipoferum SP7 and the C. dactylon root isolate displayed the unique features of being denitrifiers as well as N2 fixers. The N2-dependent growth curve was biphasic: cells in younger cultures showed the characteristic spiral shape and motility, but those in older cultures developed larger, nonmotile, cystlike forms. Nitrogenase activity seemed associated only with younger spiral forms. The red pigment may be a b- or c-type cytochrome. The strong red color, which this strain develops, could be used as a marker in evaluating soil inoculation experiments."}
{"id": "PMID:22312", "title": "The distribution of enzymes in the epidermis of the domestic cat.", "content": "With the help of enzyme histochemical methods, the distribution and activities of several oxidative and hydrolytic enzymes in the epidermis of the densely-haired domestic cat have been studied. Distinct oxidative enzyme activity could be demonstrated in all epidermal layers except the stratum corneum. Among the hydrolytic enzymes investigated, strong reactions for non-specific esterases were visible especially in the str. granulosum and the basal lamellae of the str. corneum. Positive reactions for cholinesterases could not be observed in the cat epidermis. The results are discussed in relation to corresponding investigations on the epidermis of sparsely-haired mammals, e.g. the domestic pig and man. Generally the enzyme pattern of the cat epidermis only shows limited parallels to man, especially where esterase distribution is concerned.", "contents": "The distribution of enzymes in the epidermis of the domestic cat. With the help of enzyme histochemical methods, the distribution and activities of several oxidative and hydrolytic enzymes in the epidermis of the densely-haired domestic cat have been studied. Distinct oxidative enzyme activity could be demonstrated in all epidermal layers except the stratum corneum. Among the hydrolytic enzymes investigated, strong reactions for non-specific esterases were visible especially in the str. granulosum and the basal lamellae of the str. corneum. Positive reactions for cholinesterases could not be observed in the cat epidermis. The results are discussed in relation to corresponding investigations on the epidermis of sparsely-haired mammals, e.g. the domestic pig and man. Generally the enzyme pattern of the cat epidermis only shows limited parallels to man, especially where esterase distribution is concerned."}
{"id": "PMID:22317", "title": "[Acid-base balance immediately after administration of an oral contraceptive (author's transl)].", "content": "An increase in breathing activity has often been described for the secretory phase of the menstrual cycle, for gravidity and after intramuscular application of corpus luteum and follicle hormone. The reason for this has been assumed to be a direct interaction of the hormones in the respiratory center. A shortly published paper dealing with 50 women under long-term treatment with a combination of oestrogenes and gestagenes for oral contraception leads the author to the assumption, that a metabolic acidosis is the primary reaction, followed by an increase in breathing activity for respiratory compensation. In a long-term study it is difficult to differentiate between primary and secondary effects. Therefore in the present experiments arterial blood has been analyzed for PaO2, PaCO2, pH and hemoglobin in 49 subjects on day 1 without hormone administration and on day 2 prior to (9.00 a.m.) after (11.00 a.m., 1.00 p.m., 4.00 p.m.) administration of a combination of oestrogene and gestagene. From the measured values O2-saturation, standard-bicarbonate, buffer bases and base excess have been calculated by the Thews nomogram. By comparison of the results before and after hormone administration it was shown, that the primary effect is a metabolic acidosis, partly compensated during the next 7 h by respiratory adaptation. There is no indication for a primary respiratory alkalosis.", "contents": "[Acid-base balance immediately after administration of an oral contraceptive (author's transl)]. An increase in breathing activity has often been described for the secretory phase of the menstrual cycle, for gravidity and after intramuscular application of corpus luteum and follicle hormone. The reason for this has been assumed to be a direct interaction of the hormones in the respiratory center. A shortly published paper dealing with 50 women under long-term treatment with a combination of oestrogenes and gestagenes for oral contraception leads the author to the assumption, that a metabolic acidosis is the primary reaction, followed by an increase in breathing activity for respiratory compensation. In a long-term study it is difficult to differentiate between primary and secondary effects. Therefore in the present experiments arterial blood has been analyzed for PaO2, PaCO2, pH and hemoglobin in 49 subjects on day 1 without hormone administration and on day 2 prior to (9.00 a.m.) after (11.00 a.m., 1.00 p.m., 4.00 p.m.) administration of a combination of oestrogene and gestagene. From the measured values O2-saturation, standard-bicarbonate, buffer bases and base excess have been calculated by the Thews nomogram. By comparison of the results before and after hormone administration it was shown, that the primary effect is a metabolic acidosis, partly compensated during the next 7 h by respiratory adaptation. There is no indication for a primary respiratory alkalosis."}
{"id": "PMID:22318", "title": "Influence of cobra venom (CoF) and pneumococcal S III capsular polysaccharide on immunologic humoral response and visceral distribution of antigens.", "content": "The immunologic response to sheep erythrocytes was compared in mice treated with Cobra venom (CoF) and with pneumococcal capsular antigen S III. Suppression of the immunologic response in both cases was attributed to the ability of both tested substances to activate the third component of complement. CoF and S III both changed the organ localization of labeled antigens capable of activating the complement system. No evidence for an alternative pathway by which S III could activate the complement system was found. On the basis of the literature data and experimental findings, the properties of CoF and S III were compared in the light of their ability to suppress the immunologic response.", "contents": "Influence of cobra venom (CoF) and pneumococcal S III capsular polysaccharide on immunologic humoral response and visceral distribution of antigens. The immunologic response to sheep erythrocytes was compared in mice treated with Cobra venom (CoF) and with pneumococcal capsular antigen S III. Suppression of the immunologic response in both cases was attributed to the ability of both tested substances to activate the third component of complement. CoF and S III both changed the organ localization of labeled antigens capable of activating the complement system. No evidence for an alternative pathway by which S III could activate the complement system was found. On the basis of the literature data and experimental findings, the properties of CoF and S III were compared in the light of their ability to suppress the immunologic response."}
{"id": "PMID:22319", "title": "Variation of human intestinal gamma-glutamyl transpeptidase in ontogenetic development.", "content": "Activity of gamma-glutamyl transpeptidase in human intestines was measured against alpha-naphthylamide and 12 gamma-glutamyl amino acids and peptides as substrate. Distinctly altered activity was found to accompany ontogenetic development. The ratio of the transpeptidase activity tested against monoglutamyl substrates in the intestines of 7-month fetuses, newborns and adults was 15:1:4, whereas the ratio of gamma-glutamyl cyclotransferase activities in the same age groups was 1-0:1-2:1-6. Distinct differences were found in resistance to heating, sensitivity to L-serine plus borate, and other effectors, and electrophoretic mobility, between fetal gamma-glutamyl transpeptidase and the enzyme from adults, which supports the hypothesis of existence of two forms of the enzyme in the human intestines. The results suggest involvement of gamma-glutamyl transpeptidase in the pathomechanism of celiakia in children.", "contents": "Variation of human intestinal gamma-glutamyl transpeptidase in ontogenetic development. Activity of gamma-glutamyl transpeptidase in human intestines was measured against alpha-naphthylamide and 12 gamma-glutamyl amino acids and peptides as substrate. Distinctly altered activity was found to accompany ontogenetic development. The ratio of the transpeptidase activity tested against monoglutamyl substrates in the intestines of 7-month fetuses, newborns and adults was 15:1:4, whereas the ratio of gamma-glutamyl cyclotransferase activities in the same age groups was 1-0:1-2:1-6. Distinct differences were found in resistance to heating, sensitivity to L-serine plus borate, and other effectors, and electrophoretic mobility, between fetal gamma-glutamyl transpeptidase and the enzyme from adults, which supports the hypothesis of existence of two forms of the enzyme in the human intestines. The results suggest involvement of gamma-glutamyl transpeptidase in the pathomechanism of celiakia in children."}
{"id": "PMID:22320", "title": "Reaction of antibody with gamma-glutamyl transpeptidase. I. Isolation of the human enzyme and inhibition of its activity by antiserum.", "content": "Use of a four-step method of purification from human kidneys yielded gamma-glutamyl transpeptidase with specific activity 330 times higher than activity in the homogenate. The enzyme from human liver was also purified, and from urine two fractions of it were separated. From rabbits immunized with the enzyme from human kidney, antiserum was obtained which inhibits and precipitates the human-derived enzyme, and in a low degree the enzyme purified from bovine kidneys. This inhibition was independent of incubation time and precipitate formation, but dependent on the amount of antiserum used. A gamma-glutamyl transpeptidase complex with antibody was isolated on a column with CM-cellulose with electrophoretic mobility different from that of the native enzyme.", "contents": "Reaction of antibody with gamma-glutamyl transpeptidase. I. Isolation of the human enzyme and inhibition of its activity by antiserum. Use of a four-step method of purification from human kidneys yielded gamma-glutamyl transpeptidase with specific activity 330 times higher than activity in the homogenate. The enzyme from human liver was also purified, and from urine two fractions of it were separated. From rabbits immunized with the enzyme from human kidney, antiserum was obtained which inhibits and precipitates the human-derived enzyme, and in a low degree the enzyme purified from bovine kidneys. This inhibition was independent of incubation time and precipitate formation, but dependent on the amount of antiserum used. A gamma-glutamyl transpeptidase complex with antibody was isolated on a column with CM-cellulose with electrophoretic mobility different from that of the native enzyme."}
{"id": "PMID:22316", "title": "[Heterogenity of the cryptorchid syndrome. Study of the pituitary gonadotropin reserve in 50 prepuberal bodys].", "content": "As compared to a control group, the study of the pituitary reserve of gonadotrophins in 50, not yet puberous, cryptorchid boys, evoked that there is a heterogeneity in cryptorchism. The LH pituitary reserve may be insufficient, normal or increased; the FSH pituitary reserve may be normal or above normal. A longitudinal study of these patients, as well as the correlations with ultra-structural and histologic studies should lead to a better understanding of the significance of the hormonal abnormalities encountered in cryptorchism, and to a better appreciation of the associated testicular changes.", "contents": "[Heterogenity of the cryptorchid syndrome. Study of the pituitary gonadotropin reserve in 50 prepuberal bodys]. As compared to a control group, the study of the pituitary reserve of gonadotrophins in 50, not yet puberous, cryptorchid boys, evoked that there is a heterogeneity in cryptorchism. The LH pituitary reserve may be insufficient, normal or increased; the FSH pituitary reserve may be normal or above normal. A longitudinal study of these patients, as well as the correlations with ultra-structural and histologic studies should lead to a better understanding of the significance of the hormonal abnormalities encountered in cryptorchism, and to a better appreciation of the associated testicular changes."}
{"id": "PMID:22321", "title": "Cobalt-activated acylase activity in experimental toxic liver damage.", "content": "Co++-activated acylase activity was studied in the blood serum and liver homogenates from rabbits poisoned with CCl4 in doses of 0-5 g/kg body weight intraperitoneally. Activity of this enzyme in serum increased on the first day after poisoning, but the rise was of short duration. Increased serum activity of the enzyme was accompanied by an increase in acylase activity in liver homogenates, which persisted to the ninth day, i.e. to the end of the observation period, when serum acylase activity returned to normal. Co++-activated acylase activity in serum was not correlated with its activity in liver homogenates. Co++-activated acylase activity was significantly correlated with AlAT and GGTP activities, but acylase and LAP were not correlated.", "contents": "Cobalt-activated acylase activity in experimental toxic liver damage. Co++-activated acylase activity was studied in the blood serum and liver homogenates from rabbits poisoned with CCl4 in doses of 0-5 g/kg body weight intraperitoneally. Activity of this enzyme in serum increased on the first day after poisoning, but the rise was of short duration. Increased serum activity of the enzyme was accompanied by an increase in acylase activity in liver homogenates, which persisted to the ninth day, i.e. to the end of the observation period, when serum acylase activity returned to normal. Co++-activated acylase activity in serum was not correlated with its activity in liver homogenates. Co++-activated acylase activity was significantly correlated with AlAT and GGTP activities, but acylase and LAP were not correlated."}
{"id": "PMID:22322", "title": "[Pathomorphology of the vessels of the microcirculatory bed of the serous membranes in systemic allergic vasculitis].", "content": "The impregnation method and micropreparation were used to study the morphological changes in vessels of the microcirculatory channel of serous membranes in systemic allergic vasculites. Inflammatory and sclerotic processes in arterioles, precapillaries, capillaries, postcapillaries, and venules were found to be accompanied by regeneration changes and complicated adaptative alteration of the intact structures of the terminal vascular bed. The paper also presents morphological data reflecting decompensation processes in local lymph and blood flow.", "contents": "[Pathomorphology of the vessels of the microcirculatory bed of the serous membranes in systemic allergic vasculitis]. The impregnation method and micropreparation were used to study the morphological changes in vessels of the microcirculatory channel of serous membranes in systemic allergic vasculites. Inflammatory and sclerotic processes in arterioles, precapillaries, capillaries, postcapillaries, and venules were found to be accompanied by regeneration changes and complicated adaptative alteration of the intact structures of the terminal vascular bed. The paper also presents morphological data reflecting decompensation processes in local lymph and blood flow."}
{"id": "PMID:22324", "title": "The gold solder, gold alloy interface.", "content": "With soldering the physical properties of the basis metal must be maintained and a minimum of molten metal is used. An examination of joints in 17 gauge platinized gold wire is made with 18 k gold solder following quenching immediately after flow and cooling in air; there is a widening of grain boundaries and intergranulation penetration in the latter method. A comparison with the cast gold joint is made. Some inclusions were noted.", "contents": "The gold solder, gold alloy interface. With soldering the physical properties of the basis metal must be maintained and a minimum of molten metal is used. An examination of joints in 17 gauge platinized gold wire is made with 18 k gold solder following quenching immediately after flow and cooling in air; there is a widening of grain boundaries and intergranulation penetration in the latter method. A comparison with the cast gold joint is made. Some inclusions were noted."}
{"id": "PMID:22325", "title": "Self-association of troponin.", "content": "Ox muscle troponin was shown by equilibrium- and velocity-sedimentation studies to undergo concentration-dependent dissociation into its constituent subunits as well as self-association in imidazole buffers, pH 6.9. The extent of troponin association was found to be strongly dependent on ionic strength and also to exhibit a dependence on pH and temperature; under conditions physiological in regard to pH, temperature and ionic strength the extent of polymerization of troponin is considerable in 2 mg/ml solutions. The ability of polymeric troponin to bind to tropomyosin has been inferred from studies of mixtures containing actin-tropomyosin and an excess of troponin over the amount required for the normal 7:1:1 actin-tropomyosin-troponin complex. These findings should be relevant to studies of reconstituted actin-tropomyosin-troponin preparations, since they signify possible chemical as well as physical differences between the gel, paracrystalline and filamentous states of the complex that result from adoption of different preparative procedures for analogues of the native thin filament.", "contents": "Self-association of troponin. Ox muscle troponin was shown by equilibrium- and velocity-sedimentation studies to undergo concentration-dependent dissociation into its constituent subunits as well as self-association in imidazole buffers, pH 6.9. The extent of troponin association was found to be strongly dependent on ionic strength and also to exhibit a dependence on pH and temperature; under conditions physiological in regard to pH, temperature and ionic strength the extent of polymerization of troponin is considerable in 2 mg/ml solutions. The ability of polymeric troponin to bind to tropomyosin has been inferred from studies of mixtures containing actin-tropomyosin and an excess of troponin over the amount required for the normal 7:1:1 actin-tropomyosin-troponin complex. These findings should be relevant to studies of reconstituted actin-tropomyosin-troponin preparations, since they signify possible chemical as well as physical differences between the gel, paracrystalline and filamentous states of the complex that result from adoption of different preparative procedures for analogues of the native thin filament."}
{"id": "PMID:22326", "title": "The state of aggregation of red deer (Cervus elaphus L.) beta-lactoglobulin preparations near neutral pH.", "content": "1. The state of aggregation of four red-deer (Cervus elaphus L.) beta-lactoglobulin preparations and a control ox beta-lactoglobulin A preparation was studied by sedimentation-equilibrium experiments at pH 6.5 and 20 degrees C. 2. Three of the deer preparations and the ox control each behaved as a monomer-dimer system, with a value of log K (where K is the association constant in litres/mol) in the range 5.4-5.5. 3. When one of these deer preparations was examined in the presence of dithiothreitol, log K appeared to decrease to 4.5.4. One deer preparation, comprising recovered material, appeared to have undergone irreversible changes and to behave like a non-equilibrating system containing monomer, dimer and trimer. 5. The sedimentation-equilibrium properties of the deer monomer was studied in 6M-guanidine hydrochloride at pH 7.0; the mol.wt. was 17600, the second virial coefficient was 3.4 x 10(-3) ml - mol - g-2, and the apparent partial specific volume 0.724 ml/g, a value indicating an appreciable decrease in volume on dissociation and denaturation.", "contents": "The state of aggregation of red deer (Cervus elaphus L.) beta-lactoglobulin preparations near neutral pH. 1. The state of aggregation of four red-deer (Cervus elaphus L.) beta-lactoglobulin preparations and a control ox beta-lactoglobulin A preparation was studied by sedimentation-equilibrium experiments at pH 6.5 and 20 degrees C. 2. Three of the deer preparations and the ox control each behaved as a monomer-dimer system, with a value of log K (where K is the association constant in litres/mol) in the range 5.4-5.5. 3. When one of these deer preparations was examined in the presence of dithiothreitol, log K appeared to decrease to 4.5.4. One deer preparation, comprising recovered material, appeared to have undergone irreversible changes and to behave like a non-equilibrating system containing monomer, dimer and trimer. 5. The sedimentation-equilibrium properties of the deer monomer was studied in 6M-guanidine hydrochloride at pH 7.0; the mol.wt. was 17600, the second virial coefficient was 3.4 x 10(-3) ml - mol - g-2, and the apparent partial specific volume 0.724 ml/g, a value indicating an appreciable decrease in volume on dissociation and denaturation."}
{"id": "PMID:22327", "title": "Tritium effect in peroxidation of ehtanol by liver catalase.", "content": "1. Simultaneous determination of the rate of appearance of 3H in water from [(1R)-1-3H1] ethanol and the rate of acetaldehyde formation in the presence of rat or ox liver catalase under conditions of steady-state generation of H2O2 allowed calculation of the 3H isotope effect. The mean value of 2.52 obtained for rat liver catalase at 37 degrees C and pH 6.3-7.7 was independent of both ethanol concentration and the rate of H2O2 generation over a wide range. At 25 degrees C a slightly lower mean value of 2.40 was obtained with the ox liver catalase. 2. Neither the product, acetaldehyde, nor 4-methylpyrazole influenced the two rates measured in the assay. 3. Relating the value obtained for the 3H isotope effect to a known value for the 2H isotope effect strongly supports the view that both values are close to the true isotope effect with the respective substituted compounds on the rate constant in the catalytic step involving scission of the C-H bond. 4. The constancy of the isotope effect under various conditions makes it possible to use it for interpretations in vivo. 5. It was established that beta-D-galactose dehydrogenase exhibits B-specificity towards the nicotinamide ring in NAD.", "contents": "Tritium effect in peroxidation of ehtanol by liver catalase. 1. Simultaneous determination of the rate of appearance of 3H in water from [(1R)-1-3H1] ethanol and the rate of acetaldehyde formation in the presence of rat or ox liver catalase under conditions of steady-state generation of H2O2 allowed calculation of the 3H isotope effect. The mean value of 2.52 obtained for rat liver catalase at 37 degrees C and pH 6.3-7.7 was independent of both ethanol concentration and the rate of H2O2 generation over a wide range. At 25 degrees C a slightly lower mean value of 2.40 was obtained with the ox liver catalase. 2. Neither the product, acetaldehyde, nor 4-methylpyrazole influenced the two rates measured in the assay. 3. Relating the value obtained for the 3H isotope effect to a known value for the 2H isotope effect strongly supports the view that both values are close to the true isotope effect with the respective substituted compounds on the rate constant in the catalytic step involving scission of the C-H bond. 4. The constancy of the isotope effect under various conditions makes it possible to use it for interpretations in vivo. 5. It was established that beta-D-galactose dehydrogenase exhibits B-specificity towards the nicotinamide ring in NAD."}
{"id": "PMID:22328", "title": "Affinity chromatography of the Neurospora NADP-specific glutamate dehydrogenase, its mutational variants and hybrid hexamers.", "content": "The synthesis of an affinity adsorbent, 8-(6-aminohexyl)aminoadenosine 2'-phosphate-Sepharose 4B, is described. The assembly of the 2'-AMP ligand and the hexanediamide spacer arm was synthesized in free solution before its attachment to the Sepharose matrix. This adsorbent retarded the hexameric NADP-specific glutamate dehydrogenase of Neurospora crassa, showing a capacity for this enzyme similar to that of comparable coenzyme-analogue adsorbents for other dehydrogenases. The enzyme was eluted either at pH 6.8 in a concentration gradient of NADP+, or at pH 8.5 in the presence of NADP+ in concentration gradients of either dicarboxylates or NaCl. Anomalous effects of dicarboxylates in facilitating elution are discussed. 2'-AMP and its derivatives, 8-bromoadenosine 2'-phosphate and 8-(l-aminohexyl)aminoadenosine 2'-phosphate, which were used in the synthesis of the adsorbent, all acted as enzyme inhibitors competitive with NADP+. The chromatographic properties of the wild-type enzyme were compared with those of mutationally modified variants containing defined amino acid substitutions. This approach was used to assess the biospecificity of adsorption and elution and the contribution of non-specific binding. The adsorbent showed a low capacity for the enzyme from mutant am1 (Ser-336 replaced by Phe), a variant that has a localized defect in NADP binding, but an otherwise almost normal conformation, suggesting that non-specific interactions are at most weak. The enzyme from mutant am3, a variant modified in a conformational equilibrium, was fully retarded by the adsorbent, but showed a significantly earlier elution position than the wild-type enzyme. This is consistent with measurements in free solution that showed the am3 enzyme to have a higher Ki for 2'-AMP than the wild-type enzyme. The enzyme from mutant am19 was eluted as two distinct peaks at both pH 6.8 and 8.5. The adsorbent was used to separate hybrid hexamers constructed in vitro by a freeze-thaw procedure from pairs of purified variants. Several chromatographically distinct peaks of differing enzymological properties were purified from each hybridization mixture in quantities of up to a few milligrams, and represented distinct species of hybrid hexamers differing in subunit ratio.", "contents": "Affinity chromatography of the Neurospora NADP-specific glutamate dehydrogenase, its mutational variants and hybrid hexamers. The synthesis of an affinity adsorbent, 8-(6-aminohexyl)aminoadenosine 2'-phosphate-Sepharose 4B, is described. The assembly of the 2'-AMP ligand and the hexanediamide spacer arm was synthesized in free solution before its attachment to the Sepharose matrix. This adsorbent retarded the hexameric NADP-specific glutamate dehydrogenase of Neurospora crassa, showing a capacity for this enzyme similar to that of comparable coenzyme-analogue adsorbents for other dehydrogenases. The enzyme was eluted either at pH 6.8 in a concentration gradient of NADP+, or at pH 8.5 in the presence of NADP+ in concentration gradients of either dicarboxylates or NaCl. Anomalous effects of dicarboxylates in facilitating elution are discussed. 2'-AMP and its derivatives, 8-bromoadenosine 2'-phosphate and 8-(l-aminohexyl)aminoadenosine 2'-phosphate, which were used in the synthesis of the adsorbent, all acted as enzyme inhibitors competitive with NADP+. The chromatographic properties of the wild-type enzyme were compared with those of mutationally modified variants containing defined amino acid substitutions. This approach was used to assess the biospecificity of adsorption and elution and the contribution of non-specific binding. The adsorbent showed a low capacity for the enzyme from mutant am1 (Ser-336 replaced by Phe), a variant that has a localized defect in NADP binding, but an otherwise almost normal conformation, suggesting that non-specific interactions are at most weak. The enzyme from mutant am3, a variant modified in a conformational equilibrium, was fully retarded by the adsorbent, but showed a significantly earlier elution position than the wild-type enzyme. This is consistent with measurements in free solution that showed the am3 enzyme to have a higher Ki for 2'-AMP than the wild-type enzyme. The enzyme from mutant am19 was eluted as two distinct peaks at both pH 6.8 and 8.5. The adsorbent was used to separate hybrid hexamers constructed in vitro by a freeze-thaw procedure from pairs of purified variants. Several chromatographically distinct peaks of differing enzymological properties were purified from each hybridization mixture in quantities of up to a few milligrams, and represented distinct species of hybrid hexamers differing in subunit ratio."}
{"id": "PMID:22339", "title": "Comparison of lorazepam and diazepam as premedicants.", "content": "A double-blind random study compared lorazepam with diazepam as i.m. premedicants in 84 healthy women undergoing uterine curettage. Anxiety, assessed by a self-rating test by the patient and by a trained observer, was reduced 90 min after both lorazepam (P less than 0.001) and diazepam (P less than 0.01). There was more sedation and a longer recovery time after lorazepam than after diazepam. Amnesia at 24 h after operation (lack of recall rather than lack of recognition) was greater after lorazepam. There was transient local discomfort at the site of the injection in most patients in both groups, but no serious effects. Local erythema was present in 12 patients who received lorazepam and 10 who received diazepam 90 min after the injection, disappearing after 24 h in the former group but remaining in the latter. The incidence of nausea, vomiting and headache in both groups was small and similar, but there was more restlessness and dizziness after diazepam in the early recovery period.", "contents": "Comparison of lorazepam and diazepam as premedicants. A double-blind random study compared lorazepam with diazepam as i.m. premedicants in 84 healthy women undergoing uterine curettage. Anxiety, assessed by a self-rating test by the patient and by a trained observer, was reduced 90 min after both lorazepam (P less than 0.001) and diazepam (P less than 0.01). There was more sedation and a longer recovery time after lorazepam than after diazepam. Amnesia at 24 h after operation (lack of recall rather than lack of recognition) was greater after lorazepam. There was transient local discomfort at the site of the injection in most patients in both groups, but no serious effects. Local erythema was present in 12 patients who received lorazepam and 10 who received diazepam 90 min after the injection, disappearing after 24 h in the former group but remaining in the latter. The incidence of nausea, vomiting and headache in both groups was small and similar, but there was more restlessness and dizziness after diazepam in the early recovery period."}
{"id": "PMID:22341", "title": "Epidermal nucleases. III. The ribonucleases of human epidermis.", "content": "Sodium acetate and sulphuric acid extracts of human epidermis can each be separated by chromatographic techniques into three or more fractions with ribonuclease activity. Eight of these fractions were compared with respect to molecular weight, pH activity profile, polyribonucleotide hydrolysis, and activity in the presence of low levels of spermidine. Sodium acetate and sulphuric acid extracts were also prepared from callus and from psoriatic lesions and compared with extracts from normal epidermis for their response to exogenous spermidine. All eight human epidermal ribonuclease fractions studied had an apparent molecular weight of 15,000 daltons. Seven of the ribonuclease fractions were optimally active at alkaline pHs (pH 7.3-7.6 in sodium phosphate and pH 8.I in Tris-HCl) while the eighth ribonuclease was most active at pH 5.6 in a citrate-phosphate buffer. All enzymes hydrolyzed polycytidylic acid and five also hydrolyzed polyuridylic acid. None hydrolyzed polyadenylic acid. Seven of the eight ribonucleases studied exhibited greater activity in the presence of added spermidine. The extracts from psoriatic scales showed markedly elevated ribonuclease levels which could not be raised further by the addition of spermidine.", "contents": "Epidermal nucleases. III. The ribonucleases of human epidermis. Sodium acetate and sulphuric acid extracts of human epidermis can each be separated by chromatographic techniques into three or more fractions with ribonuclease activity. Eight of these fractions were compared with respect to molecular weight, pH activity profile, polyribonucleotide hydrolysis, and activity in the presence of low levels of spermidine. Sodium acetate and sulphuric acid extracts were also prepared from callus and from psoriatic lesions and compared with extracts from normal epidermis for their response to exogenous spermidine. All eight human epidermal ribonuclease fractions studied had an apparent molecular weight of 15,000 daltons. Seven of the ribonuclease fractions were optimally active at alkaline pHs (pH 7.3-7.6 in sodium phosphate and pH 8.I in Tris-HCl) while the eighth ribonuclease was most active at pH 5.6 in a citrate-phosphate buffer. All enzymes hydrolyzed polycytidylic acid and five also hydrolyzed polyuridylic acid. None hydrolyzed polyadenylic acid. Seven of the eight ribonucleases studied exhibited greater activity in the presence of added spermidine. The extracts from psoriatic scales showed markedly elevated ribonuclease levels which could not be raised further by the addition of spermidine."}
{"id": "PMID:22342", "title": "Enzymes of galactose metabolism in human hair roots.", "content": "Micro-methods, making use of radioactive substrates, are described for the quantitative estimation of galactokinase and galactose-1-phosphate uridyl transferase activities in lysates of hair roots obtained from the human scalp. Enzyme assays can be carried out with fractions of one hair root. Both enzymes have been investigated with regard to stability, pH optimum and Michaelis-Menten constants. Along with similarities there were also certain differences as compared to galactokinase and galactose-1-phosphate uridyl transferase activities in other human tissues. The findings were used to optimise and standardise a radiochemical micro-assay for both enzymes in human hair root lysates, applicable to carrier detection studies in galactosaemia, an inborn error of carbohydrate metabolism. Because they can easily be obtained, hair roots are a very suitable biopsy material for both fundamental and diagnostic investigations of these enzymes.", "contents": "Enzymes of galactose metabolism in human hair roots. Micro-methods, making use of radioactive substrates, are described for the quantitative estimation of galactokinase and galactose-1-phosphate uridyl transferase activities in lysates of hair roots obtained from the human scalp. Enzyme assays can be carried out with fractions of one hair root. Both enzymes have been investigated with regard to stability, pH optimum and Michaelis-Menten constants. Along with similarities there were also certain differences as compared to galactokinase and galactose-1-phosphate uridyl transferase activities in other human tissues. The findings were used to optimise and standardise a radiochemical micro-assay for both enzymes in human hair root lysates, applicable to carrier detection studies in galactosaemia, an inborn error of carbohydrate metabolism. Because they can easily be obtained, hair roots are a very suitable biopsy material for both fundamental and diagnostic investigations of these enzymes."}
{"id": "PMID:22344", "title": "Tobacco mosaic virus protein: sedimentation equilibrium studies of the initial stages of polymerization.", "content": "The lowest stages of polymerization of tobacco mosaic virus protein were studied by means of high-speed sedimentation equilibrium experiments. Several distinct modes of polymerization were found. At pH 7.1 the expected monomer-trimer-higher polymer equilibrium was observed--very little dimer was detected at this pH. At pH 7.5, however, a strong dimerization was observed--neither monomer nor trimer was detected at this pH. An octamer appeared to be the only species present other than the dimer. When 0.01 M beta-mercaptoethanol was added to the solvent pH 7.5, the dimer was dissociated, resulting in a monomer-trimer association. The dimerization may be the basis for the larger \"doubled\" polymers formed by the protein at alkaline pH, while the octamer may correspond to the 8S peak frequently observed in sedimentation velocity experiments at alkaline pH. On the other hand, the monomer-trimer-higher polymer equilibrium may correspond to the single helix formed by the protein at slightly acid pH and to the combination of 4S and 20S peaks seen in sedimentation velocity experiments at slightly acid pH.", "contents": "Tobacco mosaic virus protein: sedimentation equilibrium studies of the initial stages of polymerization. The lowest stages of polymerization of tobacco mosaic virus protein were studied by means of high-speed sedimentation equilibrium experiments. Several distinct modes of polymerization were found. At pH 7.1 the expected monomer-trimer-higher polymer equilibrium was observed--very little dimer was detected at this pH. At pH 7.5, however, a strong dimerization was observed--neither monomer nor trimer was detected at this pH. An octamer appeared to be the only species present other than the dimer. When 0.01 M beta-mercaptoethanol was added to the solvent pH 7.5, the dimer was dissociated, resulting in a monomer-trimer association. The dimerization may be the basis for the larger \"doubled\" polymers formed by the protein at alkaline pH, while the octamer may correspond to the 8S peak frequently observed in sedimentation velocity experiments at alkaline pH. On the other hand, the monomer-trimer-higher polymer equilibrium may correspond to the single helix formed by the protein at slightly acid pH and to the combination of 4S and 20S peaks seen in sedimentation velocity experiments at slightly acid pH."}
{"id": "PMID:22345", "title": "Factors affecting the adenosine triphosphate induced release of iron from transferrin.", "content": "The release of iron from transferrin was investigated by incubating the diferric protein in the presence of potential iron-releasing agents. The effective chemical group appears to be pyrophosphate, which is present in blood cells as nucleoside di- and triphosphates, notably adenosine triphosphate (ATP). An alternative structure with comparable activity is represented by 2,3-diphosphoglycerate. Neither 1 mM adenosine monophosphate (AMP) nor 1 mM orthophosphate released iron from transferrin. The ATP-induced iron-releasing activity was dependent on weak acidic conditions and was sensitive to temperature and sodium chloride concentration. The rate of iron release rapidly increased as transferrin was titrated with HCl from pH 6.8 to 6.1 in the presence of 1 mM ATP and 160 mM NaCl at 20 degrees C. Iron release from transferrin without ATP was observed below pH 5.5. Ascorbate (10(-4) M) reduced Fe(III), but only after iron release from transferrin by a physiological concentration of ATP. A proposal for the mechanism of iron release from transferrin by ATP and the utilization of reduced iron by erythroid cells is described.", "contents": "Factors affecting the adenosine triphosphate induced release of iron from transferrin. The release of iron from transferrin was investigated by incubating the diferric protein in the presence of potential iron-releasing agents. The effective chemical group appears to be pyrophosphate, which is present in blood cells as nucleoside di- and triphosphates, notably adenosine triphosphate (ATP). An alternative structure with comparable activity is represented by 2,3-diphosphoglycerate. Neither 1 mM adenosine monophosphate (AMP) nor 1 mM orthophosphate released iron from transferrin. The ATP-induced iron-releasing activity was dependent on weak acidic conditions and was sensitive to temperature and sodium chloride concentration. The rate of iron release rapidly increased as transferrin was titrated with HCl from pH 6.8 to 6.1 in the presence of 1 mM ATP and 160 mM NaCl at 20 degrees C. Iron release from transferrin without ATP was observed below pH 5.5. Ascorbate (10(-4) M) reduced Fe(III), but only after iron release from transferrin by a physiological concentration of ATP. A proposal for the mechanism of iron release from transferrin by ATP and the utilization of reduced iron by erythroid cells is described."}
{"id": "PMID:22346", "title": "Gated proton conduction via the coupling factor of photophosphorylation modified by N,-N-orthophenyldimaleimide.", "content": "The membrane bound coupling factor of photophosphorylation is studied after pretreatment of broken chloroplasts with the bifunctional N,N-orthophenyldimaleimide under energization of the thylakoid membrane by mild flashing light. The proton conduction of the membrane is monitored both via the electrochromic absorption changes and via selective pH-indicating dyes. It is found that the coupling factor, after interaction with N,N-orthophenyldimaleimide during the preillumination period, shortcircuits one of the two protons pumped inside after excitation of chloroplasts with one short flash of light. In contrast to the low proton conductivity of the unperturbed thylakoid membrane (relaxation time for a proton gradient greater than 5s), this extra proton channel leads to a partial relaxation of a proton gradient within a few ms. Although limited to only one proton per electron, this extra proton conducting pathway is not otherwise specific. It operates with protons resulting from both Photosystem I and Photosystem II activity. In addition it operates with protons already present in the internal phase before firing of the exciting light flash. These effects are prevented by the presence of ATP (but not GTP) during the preillumination period. It is suggested that the modified coupling factor is gated open by the light induced electric field across the thylakoid membrane while self closing after passage of one proton per activated coupling factor.", "contents": "Gated proton conduction via the coupling factor of photophosphorylation modified by N,-N-orthophenyldimaleimide. The membrane bound coupling factor of photophosphorylation is studied after pretreatment of broken chloroplasts with the bifunctional N,N-orthophenyldimaleimide under energization of the thylakoid membrane by mild flashing light. The proton conduction of the membrane is monitored both via the electrochromic absorption changes and via selective pH-indicating dyes. It is found that the coupling factor, after interaction with N,N-orthophenyldimaleimide during the preillumination period, shortcircuits one of the two protons pumped inside after excitation of chloroplasts with one short flash of light. In contrast to the low proton conductivity of the unperturbed thylakoid membrane (relaxation time for a proton gradient greater than 5s), this extra proton channel leads to a partial relaxation of a proton gradient within a few ms. Although limited to only one proton per electron, this extra proton conducting pathway is not otherwise specific. It operates with protons resulting from both Photosystem I and Photosystem II activity. In addition it operates with protons already present in the internal phase before firing of the exciting light flash. These effects are prevented by the presence of ATP (but not GTP) during the preillumination period. It is suggested that the modified coupling factor is gated open by the light induced electric field across the thylakoid membrane while self closing after passage of one proton per activated coupling factor."}
{"id": "PMID:22349", "title": "Effects of dietary vitamin B-2 and vitamin E on the delta9-desaturase and catalase activities in the rat liver microsomes.", "content": "The effects of dietary vitamin B-2 and vitamin E on delta9-desaturation  of stearoyl-CoA, catalase, glutathione peroxidase, superoxide dismutase and electron transport components in rat liver microsomes have been investigated. delta9-desaturase activities were decreased on diets deficient of vitamin B-2, E and supplemented with E. Among the peroxide-scavenging enzymes, only the catalase activity in microsomes correlates significantly with delta9-desaturase activity. In vitro addition of bovine catalase had no effect on microsomal delta9-desaturase activity on control diet. However, it enhanced the delta9-desaturation in microsomes on vitamin B-2-deficient diet which contained low catalase and high superoxide dismutase activities, compared to those in microsomes of control diet. It is suggested that the hydrogen peroxide-generating and -decomposing systems may play an important role on the delta9-desaturase activity in microsomes.", "contents": "Effects of dietary vitamin B-2 and vitamin E on the delta9-desaturase and catalase activities in the rat liver microsomes. The effects of dietary vitamin B-2 and vitamin E on delta9-desaturation  of stearoyl-CoA, catalase, glutathione peroxidase, superoxide dismutase and electron transport components in rat liver microsomes have been investigated. delta9-desaturase activities were decreased on diets deficient of vitamin B-2, E and supplemented with E. Among the peroxide-scavenging enzymes, only the catalase activity in microsomes correlates significantly with delta9-desaturase activity. In vitro addition of bovine catalase had no effect on microsomal delta9-desaturase activity on control diet. However, it enhanced the delta9-desaturation in microsomes on vitamin B-2-deficient diet which contained low catalase and high superoxide dismutase activities, compared to those in microsomes of control diet. It is suggested that the hydrogen peroxide-generating and -decomposing systems may play an important role on the delta9-desaturase activity in microsomes."}
{"id": "PMID:22351", "title": "The polymerization pattern of zinc(II)-insulin at pH 7.0.", "content": "Sedimentation equilibrium experiments were conducted at pH 7.0 using solutions of bovine insulin containing 2 mol of zinc(II) ions per six base-mol of insulin. A detailed analysis of these results revealed the existence of a stable zinc-insulin hexamer together with linked polymerization reactions. Specifically these are a background polymerization of zinc-free insulin as previously described by Jeffrey et al. ((1976) Biochemistry 15, 4660--4665) and a slight tendency for the zinc-insulin hexamer to undergo indefinite self-association. Equilibrium constants governing these reactions are reported together with equations which permit calculation of the composition of the solution at any given total concentration. Comment is made on the possible biological significance of this linked polymerization pattern, and on the likely identity of the structure of the stable zinc-insulin hexamer with that previously reported from X-ray crystallographic studies.", "contents": "The polymerization pattern of zinc(II)-insulin at pH 7.0. Sedimentation equilibrium experiments were conducted at pH 7.0 using solutions of bovine insulin containing 2 mol of zinc(II) ions per six base-mol of insulin. A detailed analysis of these results revealed the existence of a stable zinc-insulin hexamer together with linked polymerization reactions. Specifically these are a background polymerization of zinc-free insulin as previously described by Jeffrey et al. ((1976) Biochemistry 15, 4660--4665) and a slight tendency for the zinc-insulin hexamer to undergo indefinite self-association. Equilibrium constants governing these reactions are reported together with equations which permit calculation of the composition of the solution at any given total concentration. Comment is made on the possible biological significance of this linked polymerization pattern, and on the likely identity of the structure of the stable zinc-insulin hexamer with that previously reported from X-ray crystallographic studies."}
{"id": "PMID:22352", "title": "On the molecular conformation of human haemopexin. I. Reactivity of the tyrosine and tryptophan side chains.", "content": "The reactivity of the aromatic side chains of Tyr and Trp in human haemopexin were studied by chemical modifications and analysis of spectrophotometric titration curves. It has turned out that: 1. Under non-denaturing conditions the aromatic rings of Tyr resisted both acetylation and nitration. 2. Three indole groups of Trp reacted with the Koshland agent, without the native conformation of the protein being markedly affected (CD spectra). 3. Oxidation by N-bromosuccinimide split the peptide chain and the molecular conformation collapsed. 4. The Tyr residues could be placed into three classes, according to their pK values: 2 (or 1 in the haem-haemopexin complex) were normally accessible to titration, 5 were masked and the remaining 7 (or 8) were buried. 5. The spectrophotometric titration curve could not be analysed in terms of the Linderstr\u00f8m-Lang equation. The findings 1 to 3 refer to both haemopexin and its complex with haem; the spectrophotometric titration curves of the two molecules are very similar too. Consequently, the binding of haem is not associated with a profound alteration of the molecular architecture. The generally low reactivity of the side chains studied indicates that the hydrophobic peptide core of this glycoprotein is a compact one, very restricted in its contacts with the environment.", "contents": "On the molecular conformation of human haemopexin. I. Reactivity of the tyrosine and tryptophan side chains. The reactivity of the aromatic side chains of Tyr and Trp in human haemopexin were studied by chemical modifications and analysis of spectrophotometric titration curves. It has turned out that: 1. Under non-denaturing conditions the aromatic rings of Tyr resisted both acetylation and nitration. 2. Three indole groups of Trp reacted with the Koshland agent, without the native conformation of the protein being markedly affected (CD spectra). 3. Oxidation by N-bromosuccinimide split the peptide chain and the molecular conformation collapsed. 4. The Tyr residues could be placed into three classes, according to their pK values: 2 (or 1 in the haem-haemopexin complex) were normally accessible to titration, 5 were masked and the remaining 7 (or 8) were buried. 5. The spectrophotometric titration curve could not be analysed in terms of the Linderstr\u00f8m-Lang equation. The findings 1 to 3 refer to both haemopexin and its complex with haem; the spectrophotometric titration curves of the two molecules are very similar too. Consequently, the binding of haem is not associated with a profound alteration of the molecular architecture. The generally low reactivity of the side chains studied indicates that the hydrophobic peptide core of this glycoprotein is a compact one, very restricted in its contacts with the environment."}
{"id": "PMID:22353", "title": "Functional properties of normal and sickle cell hemoglobins in polyethylene glycol 6000.", "content": "The functional properties of human hemoglobin A and S were studied in concentrated solutions of polyethylene glycol. Polyethylene glycol solutions are frequently used as media for protein crystallization. In particular, sickle cell hemoglobin, which does not make X-ray quality crystals in high salt solutions, will form high-quality crystals in polyethylene glycol. Comparison of the functional properties of normal and sickle cell hemoglobin in polyethylene glycol show that pH, anion effects and cooperativity of ligand binding are largely unaffected by polyethylene glycol. This suggests that the crystals grown in this medium are representative of the native structure.", "contents": "Functional properties of normal and sickle cell hemoglobins in polyethylene glycol 6000. The functional properties of human hemoglobin A and S were studied in concentrated solutions of polyethylene glycol. Polyethylene glycol solutions are frequently used as media for protein crystallization. In particular, sickle cell hemoglobin, which does not make X-ray quality crystals in high salt solutions, will form high-quality crystals in polyethylene glycol. Comparison of the functional properties of normal and sickle cell hemoglobin in polyethylene glycol show that pH, anion effects and cooperativity of ligand binding are largely unaffected by polyethylene glycol. This suggests that the crystals grown in this medium are representative of the native structure."}
{"id": "PMID:22355", "title": "Biosynthesis of beta-glucans by cell-free extracts from Saccharomyces cerevisiae.", "content": "Cell-free extracts from Saccharomyces cerevisiae catalyzed the incorporation of glucosyl residues from UDP-[U-14C]glucose into beta-1,3-glucans which contained a significant proportion of beta-1,6-glycosidic linkages. When GDP-[U-14C]glucose was used as substrate only trace amounts of glucose were incorporated. Activity of beta-glucan synthetase was distributed among membrane and cell wall fractions, specific activity being higher in this latter. Beta-glucan synthesized by membrane and cell wall fractions contained 0.6% and 2.5% of beta-1,6-glycosidic linkages respectively. A marked decrease in the activity of beta-glucan synthetase occurred as the cells aged. Significant activity of glycogen synthetase was detected only in cells which had reached the stationary phase of growth.", "contents": "Biosynthesis of beta-glucans by cell-free extracts from Saccharomyces cerevisiae. Cell-free extracts from Saccharomyces cerevisiae catalyzed the incorporation of glucosyl residues from UDP-[U-14C]glucose into beta-1,3-glucans which contained a significant proportion of beta-1,6-glycosidic linkages. When GDP-[U-14C]glucose was used as substrate only trace amounts of glucose were incorporated. Activity of beta-glucan synthetase was distributed among membrane and cell wall fractions, specific activity being higher in this latter. Beta-glucan synthesized by membrane and cell wall fractions contained 0.6% and 2.5% of beta-1,6-glycosidic linkages respectively. A marked decrease in the activity of beta-glucan synthetase occurred as the cells aged. Significant activity of glycogen synthetase was detected only in cells which had reached the stationary phase of growth."}
{"id": "PMID:22359", "title": "[Light-dependent uptake of hydrogen ions in chloroplasts and chromatophores: effects of hearing, solvents and detergents].", "content": "The effects of heating, organic solvents and detergents on the light-dependent hydrogen ion uptake in chloroplasts and chromatophores and the coupled photophosphorylation were compared. It was shown that the membrane structure of the chromatophores is much more stable than that of the chloroplast thylacoids. The activation of the pH function in the chromatophores in the presence of low concentrations of diethyl ether and detergents was noted. The effects observed may be due to the changes in the physico-chemical properties of the membranes rather than to the direct effect on the photosynthetic electron transfer chain.", "contents": "[Light-dependent uptake of hydrogen ions in chloroplasts and chromatophores: effects of hearing, solvents and detergents]. The effects of heating, organic solvents and detergents on the light-dependent hydrogen ion uptake in chloroplasts and chromatophores and the coupled photophosphorylation were compared. It was shown that the membrane structure of the chromatophores is much more stable than that of the chloroplast thylacoids. The activation of the pH function in the chromatophores in the presence of low concentrations of diethyl ether and detergents was noted. The effects observed may be due to the changes in the physico-chemical properties of the membranes rather than to the direct effect on the photosynthetic electron transfer chain."}
{"id": "PMID:22360", "title": "[Nad-dependent formate dehydrogenase from methylotrophic bacteria. Characteristics and stability of soluble and immobilized enzyme].", "content": "pH-dependency is studied of kinetic parameters of the reaction catalyzed by NAD-dependent formate dehydrogenase from methylotrophic Bacterium spl strain. Values of Km for NAD and formate, and also of maximum reaction rate are found not to change within the pH range from 6 to 9. Role of SH-groups in the development of the enzyme catalytic activity and the effect of different factors on stability of soluble and immobilized enzyme forms are investigated. Molecular weight of the enzyme (70000), extinction coefficient and catalytical constant (6 s-1) are determined.", "contents": "[Nad-dependent formate dehydrogenase from methylotrophic bacteria. Characteristics and stability of soluble and immobilized enzyme]. pH-dependency is studied of kinetic parameters of the reaction catalyzed by NAD-dependent formate dehydrogenase from methylotrophic Bacterium spl strain. Values of Km for NAD and formate, and also of maximum reaction rate are found not to change within the pH range from 6 to 9. Role of SH-groups in the development of the enzyme catalytic activity and the effect of different factors on stability of soluble and immobilized enzyme forms are investigated. Molecular weight of the enzyme (70000), extinction coefficient and catalytical constant (6 s-1) are determined."}
{"id": "PMID:22357", "title": "[Photoinduced inhibition and stimulation of respiration in cells of Halobacterium halobiums kinetics, action spectra, relationship to photoinduction of deltapH].", "content": "Along with the inhibition illumination also causes the stimulation of the respiration of H. halobium R1 cells. When light is switched off photoinhibition of respiration (PIR) decays much faster (tau 1/2=12 sec) than photostimulation (PSR) (tau 1/2=60 sec). This allows the evaluation of the contribution of the each phase into the total change of the respiration rate. PIR prevails in neutral and alkaline media (at pH 6.8 the amplitude ratio of PSR/PIR=0.3). At the same conditions light induced alkalization of the medium is observed, which at high light intensities is followed by acidification. The half rise time of PIR is 0.5 divided by 0.8 sec under excitation with short light flashes at 18C and pH 6.8. When pH of the medium is reduced the rate of dark respiration decreases, PSR amplitude increases, PIR is almost not changed and light-induced alkalinization of the medium decreases. At pH 5.5 PSR prevails: at light of 10(5) erg/(cm(2).s) the ratio PSR/PIR=2. The maximum value of PIR and PSR at 18C reaches 20-30 percent of the dark respiration level. Uncouplers (CCCP, DNF) and inhibitor (DCCD) of phosphorylation suppress PIR and light induced alkalinization of the medium and significantly (5-7 times at Ph 6.8) increase PSR and light induced acidification. The action spectra show that bacteriorhodopsin is responsible for all the observed light induced changes of O2 and H+ exchange; carotinoids do not participate in sensibilization. It is suggested that photophosphorylation is necessary for PIR and that PSR is caused by the rise of internal pH due to light induced efflux of protons mediated by bacteriorhodopsin.", "contents": "[Photoinduced inhibition and stimulation of respiration in cells of Halobacterium halobiums kinetics, action spectra, relationship to photoinduction of deltapH]. Along with the inhibition illumination also causes the stimulation of the respiration of H. halobium R1 cells. When light is switched off photoinhibition of respiration (PIR) decays much faster (tau 1/2=12 sec) than photostimulation (PSR) (tau 1/2=60 sec). This allows the evaluation of the contribution of the each phase into the total change of the respiration rate. PIR prevails in neutral and alkaline media (at pH 6.8 the amplitude ratio of PSR/PIR=0.3). At the same conditions light induced alkalization of the medium is observed, which at high light intensities is followed by acidification. The half rise time of PIR is 0.5 divided by 0.8 sec under excitation with short light flashes at 18C and pH 6.8. When pH of the medium is reduced the rate of dark respiration decreases, PSR amplitude increases, PIR is almost not changed and light-induced alkalinization of the medium decreases. At pH 5.5 PSR prevails: at light of 10(5) erg/(cm(2).s) the ratio PSR/PIR=2. The maximum value of PIR and PSR at 18C reaches 20-30 percent of the dark respiration level. Uncouplers (CCCP, DNF) and inhibitor (DCCD) of phosphorylation suppress PIR and light induced alkalinization of the medium and significantly (5-7 times at Ph 6.8) increase PSR and light induced acidification. The action spectra show that bacteriorhodopsin is responsible for all the observed light induced changes of O2 and H+ exchange; carotinoids do not participate in sensibilization. It is suggested that photophosphorylation is necessary for PIR and that PSR is caused by the rise of internal pH due to light induced efflux of protons mediated by bacteriorhodopsin."}
{"id": "PMID:22358", "title": "[Form of the tropocollagen macromolecule].", "content": "It has been shown with electron microscope that the form of the tropocollagen macro-molecule in solution is determined by hydrogen ions concentration. It is proposed that in native collagen fibrils the tropocollagen macromolecules have an unknown before form of rods with the thickened central part. Their length is about 1000 A. The known extended form of the tropocollagen macromolecule (the rod of 2800 A length) is probably transformed to the described form by the folding of the macromolecule. The origin of cross striation of the collagen fibril is discussed.", "contents": "[Form of the tropocollagen macromolecule]. It has been shown with electron microscope that the form of the tropocollagen macro-molecule in solution is determined by hydrogen ions concentration. It is proposed that in native collagen fibrils the tropocollagen macromolecules have an unknown before form of rods with the thickened central part. Their length is about 1000 A. The known extended form of the tropocollagen macromolecule (the rod of 2800 A length) is probably transformed to the described form by the folding of the macromolecule. The origin of cross striation of the collagen fibril is discussed."}
{"id": "PMID:22369", "title": "The early assessment for individualized treatment in the prune belly syndrome.", "content": "Patients with prune belly syndrome present a spectrum of abnormality, both in the abdominal wall and the urinary tract. Ureteral pathology has characteristic features and the ureter may be more severely involved at the bladder end than in its upper portion. Early neonatal investigation is required to determine which patient can be treated in a conservative manner and which require neonatal reconstruction or temporary vesical or upper tract drainage.", "contents": "The early assessment for individualized treatment in the prune belly syndrome. Patients with prune belly syndrome present a spectrum of abnormality, both in the abdominal wall and the urinary tract. Ureteral pathology has characteristic features and the ureter may be more severely involved at the bladder end than in its upper portion. Early neonatal investigation is required to determine which patient can be treated in a conservative manner and which require neonatal reconstruction or temporary vesical or upper tract drainage."}
{"id": "PMID:22370", "title": "[Effect of dipyroxime on the concentration of nicotinamide coenzymes and adenylate nucleotides in the myocardium and liver of rats poisoned with phthalophos].", "content": "Experiments were conducted on rats; in depression of blood cholinesterase activity by 68.6 percent phthalafos proved to decrease the myocardial nicotinamide coenzymes content on account of reduction in the amount of the oxidized forms. In the liver phthalafos diminished the content of oxidized and reduced forms of nicotinamide coenzymes, decreased the level of adenylic nucleotides chiefly at the expense of ATP. Diproxim prevented the changes caused by phthalafos in blood cholinesterase reactivation to 47.5 percent. It is supposed that the capacity of diproxim to normalize the oxidative processes in the cell by acting upon the nicotinamide coenzymes and adenylic nucleotides underlies its antidote action.", "contents": "[Effect of dipyroxime on the concentration of nicotinamide coenzymes and adenylate nucleotides in the myocardium and liver of rats poisoned with phthalophos]. Experiments were conducted on rats; in depression of blood cholinesterase activity by 68.6 percent phthalafos proved to decrease the myocardial nicotinamide coenzymes content on account of reduction in the amount of the oxidized forms. In the liver phthalafos diminished the content of oxidized and reduced forms of nicotinamide coenzymes, decreased the level of adenylic nucleotides chiefly at the expense of ATP. Diproxim prevented the changes caused by phthalafos in blood cholinesterase reactivation to 47.5 percent. It is supposed that the capacity of diproxim to normalize the oxidative processes in the cell by acting upon the nicotinamide coenzymes and adenylic nucleotides underlies its antidote action."}
{"id": "PMID:22373", "title": "Ammonia absorption from the canine colon after portacaval shunt.", "content": "Ammonia absorption was studied from Thirty-Vella colon loops in 6 dogs. Four underwent an end-to-side portacaval shunt and it was shown that absorption of ammonia from the colon significantly increased postoperatively. Absorption of ammonia from various solutions was also measured before and after portacaval shunt and it was shown taht absorption was increased from a high pH solution and from a solution with a high bicarbonate content and reduced from a low pH, low osmolality and high osmolality solution. Increased deposits of stainable iron were demonstrated in the livers of dogs following portacaval shunt.", "contents": "Ammonia absorption from the canine colon after portacaval shunt. Ammonia absorption was studied from Thirty-Vella colon loops in 6 dogs. Four underwent an end-to-side portacaval shunt and it was shown that absorption of ammonia from the colon significantly increased postoperatively. Absorption of ammonia from various solutions was also measured before and after portacaval shunt and it was shown taht absorption was increased from a high pH solution and from a solution with a high bicarbonate content and reduced from a low pH, low osmolality and high osmolality solution. Increased deposits of stainable iron were demonstrated in the livers of dogs following portacaval shunt."}
{"id": "PMID:22381", "title": "Sequelae after the intravenous injection of three benzodiazepines--diazepam, lorazepam, and flunitrazepam.", "content": "The occurrence of thrombosis and phlebitis after intravenous injection of 10 mg diazepam, 4 mg lorazepam, or 1-2 mg flunitrazepam was studied on the second or third and the seventh to 10th days. A significantly higher incidence occurred with all drugs on days 7 to 10 than on days 2 and 3. Painless thrombosis occurred much more often with diazepam than with the other two benzodiazepines. Its incidence was greater in small hand or arm veins than in large antecubital vessels. Lorazepam and flunitrazepam therefore have clear advantages over diazepam.", "contents": "Sequelae after the intravenous injection of three benzodiazepines--diazepam, lorazepam, and flunitrazepam. The occurrence of thrombosis and phlebitis after intravenous injection of 10 mg diazepam, 4 mg lorazepam, or 1-2 mg flunitrazepam was studied on the second or third and the seventh to 10th days. A significantly higher incidence occurred with all drugs on days 7 to 10 than on days 2 and 3. Painless thrombosis occurred much more often with diazepam than with the other two benzodiazepines. Its incidence was greater in small hand or arm veins than in large antecubital vessels. Lorazepam and flunitrazepam therefore have clear advantages over diazepam."}
{"id": "PMID:22389", "title": "Evidence concerning the anatomical location of the dopamine stimulated adenylate cyclase in the substantia nigra.", "content": "The dopamine (DA)-sensitive adenylate cyclase in the substantia nigra was assayed in rats which had been subjected to 3 different kinds of brain lesion: (1) unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle; (2) unilateral lesions of the descending strio-nigral and pallido-nigral projections; (3) total lesions of the serotoninergic raphe-nigral pathway. Lesions of the medial forebrain bundle causing 97% depletion of striatal DA, 72% depletion of nigral tyrosine hydroxylase, and no change in nigral glutamate decarboxylase (GAD), resulted in no change in basal or DA-stimulated cyclic AMP production ipsilateral to the injection. Lesions of the globus pallidus, causing 70% and 79% reductions in GAD and substance P respectively in the ipsilateral nigra, produced a reduction in basal cyclic AMP production and abolished the normal increase in cyclic AMP produced by DA on the side of the lesion. Lesions to the dorsal and median raphe nuclei did not affect the normal DA-sensitive adenylate cyclase response in the nigra. The results suggest that one of the neurotransmitter functions of DA in this brain region may be to modulate the release of psi-aminobutyric acid (GABA) or substance P from synaptic terminals afferent to the nigra.", "contents": "Evidence concerning the anatomical location of the dopamine stimulated adenylate cyclase in the substantia nigra. The dopamine (DA)-sensitive adenylate cyclase in the substantia nigra was assayed in rats which had been subjected to 3 different kinds of brain lesion: (1) unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle; (2) unilateral lesions of the descending strio-nigral and pallido-nigral projections; (3) total lesions of the serotoninergic raphe-nigral pathway. Lesions of the medial forebrain bundle causing 97% depletion of striatal DA, 72% depletion of nigral tyrosine hydroxylase, and no change in nigral glutamate decarboxylase (GAD), resulted in no change in basal or DA-stimulated cyclic AMP production ipsilateral to the injection. Lesions of the globus pallidus, causing 70% and 79% reductions in GAD and substance P respectively in the ipsilateral nigra, produced a reduction in basal cyclic AMP production and abolished the normal increase in cyclic AMP produced by DA on the side of the lesion. Lesions to the dorsal and median raphe nuclei did not affect the normal DA-sensitive adenylate cyclase response in the nigra. The results suggest that one of the neurotransmitter functions of DA in this brain region may be to modulate the release of psi-aminobutyric acid (GABA) or substance P from synaptic terminals afferent to the nigra."}
{"id": "PMID:22391", "title": "The effects of postnatal hyper- and hypothyroidism on the development of D-amino acid oxidase in rat cerebellum and brain stem.", "content": "Treatment of rats with propylthiouracil for the first 30 days of postnatal life drastically retards the ontogenesis of D-amino acid oxidase in the brain stem and cerebellum. There is a marked terminal deficit of D-AAO in both the brain stem (--64%) and cerebellum (--67%) at 94 days (adults) despite the near euthyroid status at this age. If initiated early enough, thyroxine replacement therapy reverses the effects of PTU on the development of D-AAO. Hyperthyroidism significantly accelerates the development of D-AAO in both brain stem and cerebellum. Nonetheless, animals treated with thyroxine the first month of life display a net deficit of cerebellar D-AAO content in adulthood. The results are discussed in terms of the localization of D-AAO in cell types especially sensitive to thyroid hormone: (1) a cell type which is among the last to derive from the external germinal zone in the developing cerebellum, and which in the adult is located adjacent to the Purkinje cell soma; and (2) mossy fiber neurons and cerebellar glomeruli.", "contents": "The effects of postnatal hyper- and hypothyroidism on the development of D-amino acid oxidase in rat cerebellum and brain stem. Treatment of rats with propylthiouracil for the first 30 days of postnatal life drastically retards the ontogenesis of D-amino acid oxidase in the brain stem and cerebellum. There is a marked terminal deficit of D-AAO in both the brain stem (--64%) and cerebellum (--67%) at 94 days (adults) despite the near euthyroid status at this age. If initiated early enough, thyroxine replacement therapy reverses the effects of PTU on the development of D-AAO. Hyperthyroidism significantly accelerates the development of D-AAO in both brain stem and cerebellum. Nonetheless, animals treated with thyroxine the first month of life display a net deficit of cerebellar D-AAO content in adulthood. The results are discussed in terms of the localization of D-AAO in cell types especially sensitive to thyroid hormone: (1) a cell type which is among the last to derive from the external germinal zone in the developing cerebellum, and which in the adult is located adjacent to the Purkinje cell soma; and (2) mossy fiber neurons and cerebellar glomeruli."}
{"id": "PMID:22394", "title": "[Comparative affinity of several standard anti-secretory agents for the intestinal cholinergic receptors of of rats and dogs].", "content": "Anticholinergic potentialities of four standard anti-secretory drugs (N-methyl-scopolammonium methylsulfate, atropine, diphemanil and prifinium) have been investigated with the help of molecular pharmacology techniques. The results gained with two different agonists (acetylcholine and carbachol) on rat and dog intestinal cholinergic receptors-jejunum and duodenum respectively-show : 1) That relative potentialities of the anticholinergic drugs (pA2) as well as those of the cholinomimetic agonists (pD2) are markedly modified according to which effector is used. 2) The N-methyl scopolammonium methylsulfate remains in any event the most potent anticholinergic drug investigated.", "contents": "[Comparative affinity of several standard anti-secretory agents for the intestinal cholinergic receptors of of rats and dogs]. Anticholinergic potentialities of four standard anti-secretory drugs (N-methyl-scopolammonium methylsulfate, atropine, diphemanil and prifinium) have been investigated with the help of molecular pharmacology techniques. The results gained with two different agonists (acetylcholine and carbachol) on rat and dog intestinal cholinergic receptors-jejunum and duodenum respectively-show : 1) That relative potentialities of the anticholinergic drugs (pA2) as well as those of the cholinomimetic agonists (pD2) are markedly modified according to which effector is used. 2) The N-methyl scopolammonium methylsulfate remains in any event the most potent anticholinergic drug investigated."}
{"id": "PMID:22395", "title": "Sodium nitroprusside: factors which attenuate its action. Studies with the isolated gracilis muscle of the dog.", "content": "In a laboratory preparation of the isolated, acutely denervated, and separately perfused canine gracilis muscle we have made the following observations: 1. At physiological pH, sodium nitroprusside significantly decreases the vascular resistance; 2. At physiological pH, cyanide significantly attenuates the effect of sodium nitroprusside; 3. In an acidaemic milieu, our data suggest that the effect of sodium nitroprusside may be attenuated. We speculate that patients who manifest resistance to the hypotensive effect of sodium nitroprusside may not normally eliminate the cyanide that is released from the biodegradation of sodium nitroprusside. They accumulate free cyanide which interferes with the action of sodium nitroprusside at the receptor level, leading to administration of more nitroprusside and setting in motion a positive feedback vicious cycle. When one is faced with the problem of an abnormal response to sodium nitroprusside in a fit patient, although many factors may be involved, we suggest that the possibility of rising blood cyanide levels and acidosis be given high priority.", "contents": "Sodium nitroprusside: factors which attenuate its action. Studies with the isolated gracilis muscle of the dog. In a laboratory preparation of the isolated, acutely denervated, and separately perfused canine gracilis muscle we have made the following observations: 1. At physiological pH, sodium nitroprusside significantly decreases the vascular resistance; 2. At physiological pH, cyanide significantly attenuates the effect of sodium nitroprusside; 3. In an acidaemic milieu, our data suggest that the effect of sodium nitroprusside may be attenuated. We speculate that patients who manifest resistance to the hypotensive effect of sodium nitroprusside may not normally eliminate the cyanide that is released from the biodegradation of sodium nitroprusside. They accumulate free cyanide which interferes with the action of sodium nitroprusside at the receptor level, leading to administration of more nitroprusside and setting in motion a positive feedback vicious cycle. When one is faced with the problem of an abnormal response to sodium nitroprusside in a fit patient, although many factors may be involved, we suggest that the possibility of rising blood cyanide levels and acidosis be given high priority."}
{"id": "PMID:22396", "title": "Sex-limited and sex-modified genetic defects in swine--cryptorchidism.", "content": "Review of published data suggests that cryptorchidism in Chester Whites and Yorkshires is caused by completely penetrant, recessive genes at two autosomal loci; in Lacombes, multifactorial modes of inheritance are more plausible. Different genetic systems control presence of the trait vs. number of sides affected; left testes are retained more often in almost all samples. Contrary to previous claims prenatal viability of homozygous males and females is normal. Genes causing cryptorchidism are unlikely to affect many other malformations in either sex, but pleiotropy is suggested to extend to economic traits such as conformation in females.", "contents": "Sex-limited and sex-modified genetic defects in swine--cryptorchidism. Review of published data suggests that cryptorchidism in Chester Whites and Yorkshires is caused by completely penetrant, recessive genes at two autosomal loci; in Lacombes, multifactorial modes of inheritance are more plausible. Different genetic systems control presence of the trait vs. number of sides affected; left testes are retained more often in almost all samples. Contrary to previous claims prenatal viability of homozygous males and females is normal. Genes causing cryptorchidism are unlikely to affect many other malformations in either sex, but pleiotropy is suggested to extend to economic traits such as conformation in females."}
{"id": "PMID:22397", "title": "Medullary carcinoma of the human thyroid in monolayer culture: morphological and cytochemical correlations.", "content": "Mechanically or enzymatically dissociated cells from three human medullary thyroid carcinomas (MTC) were grown in monolayer culture for periods up to seven months. Cultures of each tumor contained clusters of small epithelial-like cells which were readily identified by phase contrast microscopy. Immunocytochemical studies and electron microscopy showed that these cells contained abundant calcitonin and numerous secretory granules. Amine-storing mechanisms were also demonstrable in these cells by formaldehyde-induced fluorescence. Homogeneous cultures of epithelial-like cells showed no evidence of transitions into fibroblast-like cells. Addition of thyroxin to the tissue culture medium appeared to promote survival of epithelial-like cells in cultures of one tumor. The ability to morphologically recognize cultured cells with endocrine activity should facilitate establishment of human MTC lines for biochemical and physiological studies.", "contents": "Medullary carcinoma of the human thyroid in monolayer culture: morphological and cytochemical correlations. Mechanically or enzymatically dissociated cells from three human medullary thyroid carcinomas (MTC) were grown in monolayer culture for periods up to seven months. Cultures of each tumor contained clusters of small epithelial-like cells which were readily identified by phase contrast microscopy. Immunocytochemical studies and electron microscopy showed that these cells contained abundant calcitonin and numerous secretory granules. Amine-storing mechanisms were also demonstrable in these cells by formaldehyde-induced fluorescence. Homogeneous cultures of epithelial-like cells showed no evidence of transitions into fibroblast-like cells. Addition of thyroxin to the tissue culture medium appeared to promote survival of epithelial-like cells in cultures of one tumor. The ability to morphologically recognize cultured cells with endocrine activity should facilitate establishment of human MTC lines for biochemical and physiological studies."}
{"id": "PMID:22398", "title": "Placenta-like alkaline phosphatases from human osteosarcoma cells.", "content": "Hormone-induced alkaline phosphatases in human osteosarcoma cells (LM) were extracted and purified. Characterization of the purified enzyme showed two distinct isoenzymes. One isoenzyme was heat labile, was homoarginine inhibited, and had the electrophoretic migration of alkaline phosphatase of human osseous origin. Immunodiffusion showed that this isoenzyme reacted positively only against anti-bone alkaline phosphatase antibodies. The second isoenzyme was heat stable, was inhibited by phenylalanie, and had the same electrophoretic migration as did alkaline phosphatase extracted from mature normal human placenta. This second isoenzyme had the same antigenicity as did the normal placental enzyme. Like the D-variant placental phenotype, this second isoenzyme was inhibited by L-leucine and ethylenediaminetetraacetic acid.", "contents": "Placenta-like alkaline phosphatases from human osteosarcoma cells. Hormone-induced alkaline phosphatases in human osteosarcoma cells (LM) were extracted and purified. Characterization of the purified enzyme showed two distinct isoenzymes. One isoenzyme was heat labile, was homoarginine inhibited, and had the electrophoretic migration of alkaline phosphatase of human osseous origin. Immunodiffusion showed that this isoenzyme reacted positively only against anti-bone alkaline phosphatase antibodies. The second isoenzyme was heat stable, was inhibited by phenylalanie, and had the same electrophoretic migration as did alkaline phosphatase extracted from mature normal human placenta. This second isoenzyme had the same antigenicity as did the normal placental enzyme. Like the D-variant placental phenotype, this second isoenzyme was inhibited by L-leucine and ethylenediaminetetraacetic acid."}
{"id": "PMID:22399", "title": "Possible sites of origin of human plasma ribonucleases as evidenced by isolation and partial characterization of ribonucleases from several human tissues.", "content": "The ribonucleases (RNases) present in a number of human tissues, including heart, brain, lung, and kidney, were purified, partially characterized, and compared in their properties to the previously described RNases from human liver, spleen, pancreas, and serum. The enzymes appeared to fall into two major classes: liver-spleen type RNase and plasma-type RNase. These two types of enzymes were present in varying proportions in all tissues examined. The extent to which the tissues studied possibly contribute to serum RNase levels is discussed.", "contents": "Possible sites of origin of human plasma ribonucleases as evidenced by isolation and partial characterization of ribonucleases from several human tissues. The ribonucleases (RNases) present in a number of human tissues, including heart, brain, lung, and kidney, were purified, partially characterized, and compared in their properties to the previously described RNases from human liver, spleen, pancreas, and serum. The enzymes appeared to fall into two major classes: liver-spleen type RNase and plasma-type RNase. These two types of enzymes were present in varying proportions in all tissues examined. The extent to which the tissues studied possibly contribute to serum RNase levels is discussed."}
{"id": "PMID:22401", "title": "Mechanisms of hypercapneic pulmonary hypertension.", "content": "The mechanisms and potential mediator of hypercapneic pulmonary hypertension are incompletely understood. We studied 18 dogs, anaesthetised and spontaneously breathing both room air and after the inhalation of a gas mixture containing 10% CO2, 20.9% O2, and 69.1% N2, to determine the role of histamine, serotonin, and acidaemia in pulmonary hypertension produced by hypercapnia. Hypercapnia increased the mean pulmonary artery pressure by 0.33 kPa (2.5 mmHg) while wedge pressure and pulmonary arteriolar resistance did not change. Cardiac output significantly increased, indicating that the pulmonary hypertensive effect of hypercapnia is mainly flow related. Neither chlorpheniramine nor methysergide had significant effects on hypercapneic pulmonary hypertension. The infusion of sodium bicarbonate corrected the pH; pulmonary artery pressure and cardiac output increased while pulmonary arteriolar resistance dropped, suggesting that the increased cardiac output masked the effect of pH on pulmonary arteriolar resistance. The lack of effect of chlorpheniramine or methysergide on pulmonary resistances indicates that the vasoconstrictive effect of increased hydrogen ion concentration which accompanies hypercapnia is attributable neither to histamine nor to serotonin release.", "contents": "Mechanisms of hypercapneic pulmonary hypertension. The mechanisms and potential mediator of hypercapneic pulmonary hypertension are incompletely understood. We studied 18 dogs, anaesthetised and spontaneously breathing both room air and after the inhalation of a gas mixture containing 10% CO2, 20.9% O2, and 69.1% N2, to determine the role of histamine, serotonin, and acidaemia in pulmonary hypertension produced by hypercapnia. Hypercapnia increased the mean pulmonary artery pressure by 0.33 kPa (2.5 mmHg) while wedge pressure and pulmonary arteriolar resistance did not change. Cardiac output significantly increased, indicating that the pulmonary hypertensive effect of hypercapnia is mainly flow related. Neither chlorpheniramine nor methysergide had significant effects on hypercapneic pulmonary hypertension. The infusion of sodium bicarbonate corrected the pH; pulmonary artery pressure and cardiac output increased while pulmonary arteriolar resistance dropped, suggesting that the increased cardiac output masked the effect of pH on pulmonary arteriolar resistance. The lack of effect of chlorpheniramine or methysergide on pulmonary resistances indicates that the vasoconstrictive effect of increased hydrogen ion concentration which accompanies hypercapnia is attributable neither to histamine nor to serotonin release."}
{"id": "PMID:22402", "title": "The innervation of the salivary gland of the tick, Boophilus microplus.", "content": "Salivary of the ixodid tick Boophilus microplus Canestrini are at least partially innervated by a branch of the pedipalpal nerve. Axons containing both large granular and smaller agranular vesicles were observed within the acini associated with all types of secretory cells. A modification of the Falk-Hillarp histochemical technique was used to demonstrate discrete areas of fluorescence within the salivary acini. It is suggested that the transmitter involved with the control of salivary activities is a catecholamine and may even be dopamine.", "contents": "The innervation of the salivary gland of the tick, Boophilus microplus. Salivary of the ixodid tick Boophilus microplus Canestrini are at least partially innervated by a branch of the pedipalpal nerve. Axons containing both large granular and smaller agranular vesicles were observed within the acini associated with all types of secretory cells. A modification of the Falk-Hillarp histochemical technique was used to demonstrate discrete areas of fluorescence within the salivary acini. It is suggested that the transmitter involved with the control of salivary activities is a catecholamine and may even be dopamine."}
{"id": "PMID:22404", "title": "In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung.", "content": "Intravenous injection of rats with 156 mumol/kg of paraquat or 140 mumol/kg of diquat produced, within 60 min, a sharp drop in the ratios of NADPH to NADP in lung. The effect persisted for a time period of at least 24 h. Exposure to 100% oxygen enhanced the toxicity of both compounds without substantially amplifying changes in the NADPH/NADP ratio. Lungs retained the capability to synthesize adenine nucleotides de novo. Electron microscopic studies showed that both paraquat and diquat damage type I alveolar cells, but only paraquat produces type II cell lesions. Although bipyridylium herbicides produce acute oxidation of NADPH in vivo, there seems not to exist a straightforward relationship between this event and cell damage.", "contents": "In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung. Intravenous injection of rats with 156 mumol/kg of paraquat or 140 mumol/kg of diquat produced, within 60 min, a sharp drop in the ratios of NADPH to NADP in lung. The effect persisted for a time period of at least 24 h. Exposure to 100% oxygen enhanced the toxicity of both compounds without substantially amplifying changes in the NADPH/NADP ratio. Lungs retained the capability to synthesize adenine nucleotides de novo. Electron microscopic studies showed that both paraquat and diquat damage type I alveolar cells, but only paraquat produces type II cell lesions. Although bipyridylium herbicides produce acute oxidation of NADPH in vivo, there seems not to exist a straightforward relationship between this event and cell damage."}
{"id": "PMID:22405", "title": "Protein and enzyme release from human leukocytes: influence of phenothiazine derivatives.", "content": "We studied the influence of chlorpromazine on the release of enzymes (beta-glucuronidase, EC 3.2.1.31; lactate dehydrogenase, EC 1.1.1.27; pyruvate kinase, 2.7.1.40) and proteins using human granulocytes isolated and maintained at 37 degrees C. Chlorpromazine had a biphasic effect on enzyme release and the inhibition of the glycolytic pathway could be demonstrated only at high concentrations of chlorpromazine, after one hour's incubation. The NAD+/NADH ratio was significantly perturbed at all the concentrations. This effect is time dependent. The action of 4 other phenothiazine derivatives made it possible to establish a relationship between their physico-chemical properties and protein release. The results are compared with those from other studies using other biological materials.", "contents": "Protein and enzyme release from human leukocytes: influence of phenothiazine derivatives. We studied the influence of chlorpromazine on the release of enzymes (beta-glucuronidase, EC 3.2.1.31; lactate dehydrogenase, EC 1.1.1.27; pyruvate kinase, 2.7.1.40) and proteins using human granulocytes isolated and maintained at 37 degrees C. Chlorpromazine had a biphasic effect on enzyme release and the inhibition of the glycolytic pathway could be demonstrated only at high concentrations of chlorpromazine, after one hour's incubation. The NAD+/NADH ratio was significantly perturbed at all the concentrations. This effect is time dependent. The action of 4 other phenothiazine derivatives made it possible to establish a relationship between their physico-chemical properties and protein release. The results are compared with those from other studies using other biological materials."}
{"id": "PMID:22406", "title": "In vitro cultivation of the sporogonic stages of Plasmodium: a review.", "content": "Complete and continuous in vitro development of the sporogonic stages of the malarial parasite has not yet been accomplished, although success with erythrocytic stages (falciparum malaria) and exoerythrocytic stages (avian malaria) has been achieved. This lag in progress appears to be due to several inherent differences between sporogony and these other sequences of development. The Trager-Jensen system for in vitro development of erythrocytic stages of Plasmodium falciparum results in the formation of gametocytes, although these gametocytes have not yet been shown to be functionally mature. An improvement in culture conditions, leading to the formation of infective gametocytes, would be an important advance. Culture systems for the transformation of gametocytes to ookinetes have been described, but whether this can be easily accomplished for falciparum malaria remains to be determined. The subsequent stages of sporogony, leading from oocyst differentiation to the formation of mature, infective sporozoites, have been successfully grown in short-term in vitro cultures. The entire developmental sequence, however, has been obtained only by overlapping successive stages in different cultures. This has established that all phases of sporogony are inherently capable of being supported in vitro. Further improvements may come through a better understanding of appropriate culture conditions.", "contents": "In vitro cultivation of the sporogonic stages of Plasmodium: a review. Complete and continuous in vitro development of the sporogonic stages of the malarial parasite has not yet been accomplished, although success with erythrocytic stages (falciparum malaria) and exoerythrocytic stages (avian malaria) has been achieved. This lag in progress appears to be due to several inherent differences between sporogony and these other sequences of development. The Trager-Jensen system for in vitro development of erythrocytic stages of Plasmodium falciparum results in the formation of gametocytes, although these gametocytes have not yet been shown to be functionally mature. An improvement in culture conditions, leading to the formation of infective gametocytes, would be an important advance. Culture systems for the transformation of gametocytes to ookinetes have been described, but whether this can be easily accomplished for falciparum malaria remains to be determined. The subsequent stages of sporogony, leading from oocyst differentiation to the formation of mature, infective sporozoites, have been successfully grown in short-term in vitro cultures. The entire developmental sequence, however, has been obtained only by overlapping successive stages in different cultures. This has established that all phases of sporogony are inherently capable of being supported in vitro. Further improvements may come through a better understanding of appropriate culture conditions."}
{"id": "PMID:22407", "title": "Biochemical and technical considerations regarding the mass production of certain parasitic protozoa.", "content": "This article summarizes the most relevant biochemical knowledge about growth factors as specific essential components of culture media, and calls attention to their significance with respect to the mass cultivation of some parasitic protozoa-e.g., Trypanosoma and Leishmania spp. and amoebae. Details of recent developments and techniques of parasite fermentation are reviewed.", "contents": "Biochemical and technical considerations regarding the mass production of certain parasitic protozoa. This article summarizes the most relevant biochemical knowledge about growth factors as specific essential components of culture media, and calls attention to their significance with respect to the mass cultivation of some parasitic protozoa-e.g., Trypanosoma and Leishmania spp. and amoebae. Details of recent developments and techniques of parasite fermentation are reviewed."}
{"id": "PMID:22408", "title": "Direct micromethod for colorimetry of serum ornithine carbamoyltransferase activity, with use of a linear standard curve.", "content": "Determination of serum ornithine carbamoyltransferase (EC 2.1.3.3) activity can be a valuable diagnostic tool in the detection of liver diseases involving cytolytic processes. I describe a micromethod for measuring this activity in serum, in which the reaction product, citrulline, is measured colorimetrically in the incubation mixture without prior deproteinization. To eliminate the interference of serum protein precipitation, the concentration of sulfuric acid in the color reagent has been decreased, without substantial loss of sensitivity. Optimizing the conditions of citrulline determination, in which antipyrine and 2,3-butanedione monoxime are used, has resulted in a linear standard curve. The color formed by citrulline is found to be stable in room lighting and sensitive only to direct sunlight. The precision of the method is inversely correlated to serum enzyme activity, the CV varying between 4.6 and 21.1%.", "contents": "Direct micromethod for colorimetry of serum ornithine carbamoyltransferase activity, with use of a linear standard curve. Determination of serum ornithine carbamoyltransferase (EC 2.1.3.3) activity can be a valuable diagnostic tool in the detection of liver diseases involving cytolytic processes. I describe a micromethod for measuring this activity in serum, in which the reaction product, citrulline, is measured colorimetrically in the incubation mixture without prior deproteinization. To eliminate the interference of serum protein precipitation, the concentration of sulfuric acid in the color reagent has been decreased, without substantial loss of sensitivity. Optimizing the conditions of citrulline determination, in which antipyrine and 2,3-butanedione monoxime are used, has resulted in a linear standard curve. The color formed by citrulline is found to be stable in room lighting and sensitive only to direct sunlight. The precision of the method is inversely correlated to serum enzyme activity, the CV varying between 4.6 and 21.1%."}
{"id": "PMID:22409", "title": "Optimization of methods for aspartate aminotransferase and alanine aminotransferase.", "content": "Conditions for accurate measurement of catalytic activity of aspartate aminotransferase and alanine aminotransferase in human serum have been reinvestigated. The basic variables (kind of buffer, buffer concentration, pH, ion effects, and the influence of pyridoxal-5-phosphate) can now be considered optimized. On this basis, the kinetic parameters of both aminotransferases were determined, i.e., Michaelis and inhibitor constants for substrates and reaction products. With a mathematical approach for two-substrate enzyme reactions the substrate concentrations were calculated from the viewpoints \"most economical,\" \"most convenient,\" and \"lowest variability.\" Also the conditions for the indicator reactions have been newly defined with respect to a kinetic model. All calculated data were rechecked experimentally and it can be shown that both approaches fully agree. Furthermore, we show that the mathematical approach allows more precise recommendations for optimized methods. For technical reasons, the catalytic activity of aspartate aminotransferase in human serum can only be measured as a 0.96 fraction of its theoretical maximum velocity, the catalytic activity of alanine aminotransferase as a 0.91 fraction. The assay conditions for a Reference Method are finally described and recommendations are made for optimized routine methods for determination of the catalytic activity of these transferases in human serum.", "contents": "Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Conditions for accurate measurement of catalytic activity of aspartate aminotransferase and alanine aminotransferase in human serum have been reinvestigated. The basic variables (kind of buffer, buffer concentration, pH, ion effects, and the influence of pyridoxal-5-phosphate) can now be considered optimized. On this basis, the kinetic parameters of both aminotransferases were determined, i.e., Michaelis and inhibitor constants for substrates and reaction products. With a mathematical approach for two-substrate enzyme reactions the substrate concentrations were calculated from the viewpoints \"most economical,\" \"most convenient,\" and \"lowest variability.\" Also the conditions for the indicator reactions have been newly defined with respect to a kinetic model. All calculated data were rechecked experimentally and it can be shown that both approaches fully agree. Furthermore, we show that the mathematical approach allows more precise recommendations for optimized methods. For technical reasons, the catalytic activity of aspartate aminotransferase in human serum can only be measured as a 0.96 fraction of its theoretical maximum velocity, the catalytic activity of alanine aminotransferase as a 0.91 fraction. The assay conditions for a Reference Method are finally described and recommendations are made for optimized routine methods for determination of the catalytic activity of these transferases in human serum."}
{"id": "PMID:22410", "title": "Use of magnesium silicate before gas-liquid chromatography for determination of \"total estrogens\" in urine during pregnancy.", "content": "The authors propose a simple, rapid, reproducible and reliable method for determination of \"total estrogens\" in urine during the last three months of pregnancy. The procedure consists of separation of free urinary estrogens, obtained after rapid hydrolysis, on a column of magnesium silicate. The estrogens are adsorbed on the column at acid pH and eluted by 1 M potassium hydroxide. Following extraction of the eluate by diethyl ether and formation of trimethylsilyl ether derivatives, the steroids are analysed by gas-liquid chromatography. This new procedure is used routinely in our laboratory, one assay being carried out in less than three hours. The results appear to be comparable to those obtained with classic methods. We wish to report the elimaination curves of \"total estrogens\" during normal pregnancies and their allowable limits.", "contents": "Use of magnesium silicate before gas-liquid chromatography for determination of \"total estrogens\" in urine during pregnancy. The authors propose a simple, rapid, reproducible and reliable method for determination of \"total estrogens\" in urine during the last three months of pregnancy. The procedure consists of separation of free urinary estrogens, obtained after rapid hydrolysis, on a column of magnesium silicate. The estrogens are adsorbed on the column at acid pH and eluted by 1 M potassium hydroxide. Following extraction of the eluate by diethyl ether and formation of trimethylsilyl ether derivatives, the steroids are analysed by gas-liquid chromatography. This new procedure is used routinely in our laboratory, one assay being carried out in less than three hours. The results appear to be comparable to those obtained with classic methods. We wish to report the elimaination curves of \"total estrogens\" during normal pregnancies and their allowable limits."}
{"id": "PMID:22411", "title": "Measurement of the alpha-mannosidase activities in human plasma by a differential assay.", "content": "A differential assay based on their difference in thermal stability has been used to measure the acidic and true intermediate alpha-mannosidases in the plasma of cntrols and individuals homozygous or heterozygous for mannosidosis. The intermediate activity was found to be independent of age, sex or mannosidosis genotype. The acidic alpha-mannosidase did not vary significantly with age or between sexes for groups of the same age. The concentrations of acidic and intermediate alpha-mannosidase showed a positive correlation for adults but not for children. The ratio of acidic to true intermediate alpha-mannosidase might therefore be a useful secondary test for the detection of adult heterozygotes for mannosidosis.", "contents": "Measurement of the alpha-mannosidase activities in human plasma by a differential assay. A differential assay based on their difference in thermal stability has been used to measure the acidic and true intermediate alpha-mannosidases in the plasma of cntrols and individuals homozygous or heterozygous for mannosidosis. The intermediate activity was found to be independent of age, sex or mannosidosis genotype. The acidic alpha-mannosidase did not vary significantly with age or between sexes for groups of the same age. The concentrations of acidic and intermediate alpha-mannosidase showed a positive correlation for adults but not for children. The ratio of acidic to true intermediate alpha-mannosidase might therefore be a useful secondary test for the detection of adult heterozygotes for mannosidosis."}
{"id": "PMID:22413", "title": "The sympathetic system in hypertension.", "content": "Several experimental observations accumulated during recent years have suggested an active participation of the sympathetic system in the pathogenesis and maintenance of hypertension in various experimental models of hypertension. The evaluation of sympathetic tone by various indirect means in human hypertension has also revealed that the sympathetic system plays an important role in the maintenance of hypertension in a subgroup of the human hypertensive population. The study of circulating catecholamines, which appears to be the best and most reliable indirect means to evaluate the sympathetic activity in the human, at present, has indicated that 25 to 40 per cent of patients with essential hypertension are characterized by higher basal circulating catecholamines and by a higher sympathetic reactivity in response to postural changes. These hyperadrenergic patients are also characterized by a higher heart rate, heart contractility, cardiac index and probably by higher plasma renin activity. The identification of these patients as a separate entity is desirable since it is possible that the evolution of the hypertensive disease and the response to therapy differ in this group of patients. The study of these patients could lead to a better understanding of the mechanisms underlying the pathogenesis of cardiovascular complications and to the development of more rational and efficient therapeutic approaches.", "contents": "The sympathetic system in hypertension. Several experimental observations accumulated during recent years have suggested an active participation of the sympathetic system in the pathogenesis and maintenance of hypertension in various experimental models of hypertension. The evaluation of sympathetic tone by various indirect means in human hypertension has also revealed that the sympathetic system plays an important role in the maintenance of hypertension in a subgroup of the human hypertensive population. The study of circulating catecholamines, which appears to be the best and most reliable indirect means to evaluate the sympathetic activity in the human, at present, has indicated that 25 to 40 per cent of patients with essential hypertension are characterized by higher basal circulating catecholamines and by a higher sympathetic reactivity in response to postural changes. These hyperadrenergic patients are also characterized by a higher heart rate, heart contractility, cardiac index and probably by higher plasma renin activity. The identification of these patients as a separate entity is desirable since it is possible that the evolution of the hypertensive disease and the response to therapy differ in this group of patients. The study of these patients could lead to a better understanding of the mechanisms underlying the pathogenesis of cardiovascular complications and to the development of more rational and efficient therapeutic approaches."}
{"id": "PMID:22415", "title": "Phaeochromocytoma.", "content": "Factors involved in the evaluation and care of patients with phaeochromocytoma have been discussed with respect to important considerations for the consulting or practising physician. Historical, physical, biochemical and other diagnostic procedures, as well as therapeutic manoeuvres have been adequately documented so that the clinician requiring additional information in depth may seek out the pertinent literature. Utilizing this manner of approach should significantly improve the care of patients with phaeochromocytoma in the hands of physicians who have not themselves had extensive experience with this disease. However, it must be emphasized that because of the potential gravity of this condition, if the physician feels insecure in the care of a patient or has further questions, he should not hesitate to seek expert advice which will benefit both the patient and himself.", "contents": "Phaeochromocytoma. Factors involved in the evaluation and care of patients with phaeochromocytoma have been discussed with respect to important considerations for the consulting or practising physician. Historical, physical, biochemical and other diagnostic procedures, as well as therapeutic manoeuvres have been adequately documented so that the clinician requiring additional information in depth may seek out the pertinent literature. Utilizing this manner of approach should significantly improve the care of patients with phaeochromocytoma in the hands of physicians who have not themselves had extensive experience with this disease. However, it must be emphasized that because of the potential gravity of this condition, if the physician feels insecure in the care of a patient or has further questions, he should not hesitate to seek expert advice which will benefit both the patient and himself."}
{"id": "PMID:22418", "title": "Do stimulant drugs improve the academic performance of hyperkinetic children? A review of outcome studies.", "content": "Stimulant drug studies based primarily on measures of teacher opinion have frequently concluded that these drugs improve the achievement of hyperkinetic children. However, a review of those studies using more objective measures of academic performance revealed few positive short-term or long-term drug effects on these measures. What few improvements have been noted can be readily attributed to better attention during testing. The major effect of the stimulants appears to be an improvement in classroom manageability rather than academic performance. It would seem that the stimulants are not able to influence those etiologic factors, other than overactivity and inattentiveness, which predispose hyperkinetic children toward school difficulties. Hence, since the goal of pediatric intervention with these children should be to enhance school performance as well as reducing hyperactive behavior, the two should be independently and objectively monitored. Since stimulant medications fail to improve the academic performance of most of these children, additional educational assistance must be provided.", "contents": "Do stimulant drugs improve the academic performance of hyperkinetic children? A review of outcome studies. Stimulant drug studies based primarily on measures of teacher opinion have frequently concluded that these drugs improve the achievement of hyperkinetic children. However, a review of those studies using more objective measures of academic performance revealed few positive short-term or long-term drug effects on these measures. What few improvements have been noted can be readily attributed to better attention during testing. The major effect of the stimulants appears to be an improvement in classroom manageability rather than academic performance. It would seem that the stimulants are not able to influence those etiologic factors, other than overactivity and inattentiveness, which predispose hyperkinetic children toward school difficulties. Hence, since the goal of pediatric intervention with these children should be to enhance school performance as well as reducing hyperactive behavior, the two should be independently and objectively monitored. Since stimulant medications fail to improve the academic performance of most of these children, additional educational assistance must be provided."}
{"id": "PMID:22416", "title": "Antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085), a newly synthesized, potent beta-adrenoreceptor antagonist.", "content": "1. The antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (opc-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs. 2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals. 3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased. 4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol. 5. It is concluded that different potencies among these beta-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; beta-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.", "contents": "Antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085), a newly synthesized, potent beta-adrenoreceptor antagonist. 1. The antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (opc-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs. 2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals. 3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased. 4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol. 5. It is concluded that different potencies among these beta-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; beta-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects."}
{"id": "PMID:22419", "title": "A model for evaluation of antianxiety drugs with the use of experimentally induced stress: Comparison of nabilone and diazepam.", "content": "Volunteer subjects were used to compare a potential antianxiety drug (nabilone, 2-mg single doses) with a standard drug (diazepam, 5-mg single doses). A double-masked design with placebo control was used. Volunteer subjects were selected on the basis of high levels of train anxiety and were tested by two anxiety-inducing procedures--the mirror drawing test and the Stroop color-word test. Anxiety induced by the experimental procedure was alleviated by diazepam and, to a lesser extent, by nabilone. Since doses of the two drugs may not have been equivalent, or the time courses identical, conclusions about their relative efficacy must be guarded. The experimental model is unusual in that antianxiety drugs can be tested in volunteer subjects for true antianxiety effects rather than for side effects, such as cognitive or motor impairment, sleepiness, or other signs of central nervous system depression.", "contents": "A model for evaluation of antianxiety drugs with the use of experimentally induced stress: Comparison of nabilone and diazepam. Volunteer subjects were used to compare a potential antianxiety drug (nabilone, 2-mg single doses) with a standard drug (diazepam, 5-mg single doses). A double-masked design with placebo control was used. Volunteer subjects were selected on the basis of high levels of train anxiety and were tested by two anxiety-inducing procedures--the mirror drawing test and the Stroop color-word test. Anxiety induced by the experimental procedure was alleviated by diazepam and, to a lesser extent, by nabilone. Since doses of the two drugs may not have been equivalent, or the time courses identical, conclusions about their relative efficacy must be guarded. The experimental model is unusual in that antianxiety drugs can be tested in volunteer subjects for true antianxiety effects rather than for side effects, such as cognitive or motor impairment, sleepiness, or other signs of central nervous system depression."}
{"id": "PMID:22420", "title": "Intracellular pH and bicarbonate concentration as determined in biopsy samples from the quadriceps muscle of man at rest.", "content": "1. A method for measuring intracellular pH and bicarbonate concentration of human muscle is described. 2. Muscle biopsies from the quadriceps muscle of 13 healthy subjects at rest were analysed for acid-labile carbon dioxide and volume of extra- and intra-cellular water. Extracellular water volume was estimated from the chloride content and intracellular water volume from the potassium content, or alternatively derived from the sample weight. 3. The measured total carbon dioxide content in muscle was 9-84+/-1-39 mmol/kg. 4. Assuming a normal membrane potential (88 mV) and PCO2 of muscle equal to venous blood, calculated intracellular pH was 7-00+/-0-06 and intracellular bicarbonate concentration was 10-2+/-1-2 mmol/l of water.", "contents": "Intracellular pH and bicarbonate concentration as determined in biopsy samples from the quadriceps muscle of man at rest. 1. A method for measuring intracellular pH and bicarbonate concentration of human muscle is described. 2. Muscle biopsies from the quadriceps muscle of 13 healthy subjects at rest were analysed for acid-labile carbon dioxide and volume of extra- and intra-cellular water. Extracellular water volume was estimated from the chloride content and intracellular water volume from the potassium content, or alternatively derived from the sample weight. 3. The measured total carbon dioxide content in muscle was 9-84+/-1-39 mmol/kg. 4. Assuming a normal membrane potential (88 mV) and PCO2 of muscle equal to venous blood, calculated intracellular pH was 7-00+/-0-06 and intracellular bicarbonate concentration was 10-2+/-1-2 mmol/l of water."}
{"id": "PMID:22421", "title": "Urine electrolyte response to 18-hydroxy-11-deoxycorticosterone in normal man.", "content": "1. To assess whether the adrenal corticosteroid 18-hydroxy-11-deoxycorticosterone [18-(OH)-DOC] affects urine electrolyte excretion in normal man, seven male volunteers received 120 microgram (353 nmol) intravenously in 1 h. This was compared with glucose (50 g/l; control) and aldosterone (80 microgram, 222 nmol) infusions in the same subjects. 2. A definite though weak antinatriuretic response to 18-(OH)DOC was observed, whereas urine potassium excretion was not altered. Aldosterone increased urine potassium excretion and reduced sodium output. Urine pH was lowered by both corticosteroids, aldosterone in general having a more marked effect. Urine volume was not altered by 18-(OH)DOC. 3. Plasma concentrations of 18-(OH)DOC and aldosterone rose approximately tenfold during their respective infusions. Compared with that of aldosterone, the metabolic clearance rate of 18-(OH)DOC was slower andits plasma half-life was longer. 4. We have been able to demonstrate that 18-(OH)DOC has a definite, albeit weak antinatriuretic action in normal man, but whether or not this corticosteroid is capable of elevating the blood pressure in man remains to be shown.", "contents": "Urine electrolyte response to 18-hydroxy-11-deoxycorticosterone in normal man. 1. To assess whether the adrenal corticosteroid 18-hydroxy-11-deoxycorticosterone [18-(OH)-DOC] affects urine electrolyte excretion in normal man, seven male volunteers received 120 microgram (353 nmol) intravenously in 1 h. This was compared with glucose (50 g/l; control) and aldosterone (80 microgram, 222 nmol) infusions in the same subjects. 2. A definite though weak antinatriuretic response to 18-(OH)DOC was observed, whereas urine potassium excretion was not altered. Aldosterone increased urine potassium excretion and reduced sodium output. Urine pH was lowered by both corticosteroids, aldosterone in general having a more marked effect. Urine volume was not altered by 18-(OH)DOC. 3. Plasma concentrations of 18-(OH)DOC and aldosterone rose approximately tenfold during their respective infusions. Compared with that of aldosterone, the metabolic clearance rate of 18-(OH)DOC was slower andits plasma half-life was longer. 4. We have been able to demonstrate that 18-(OH)DOC has a definite, albeit weak antinatriuretic action in normal man, but whether or not this corticosteroid is capable of elevating the blood pressure in man remains to be shown."}
{"id": "PMID:22417", "title": "Drug kinetics and artificial kidneys.", "content": "The factors affecting solute movement across the membrane during haemodialysis are well understood. Likewise the mathematics of drug kinetics are well described. However, studies of the effects of artificial kidneys on drug kinetics have often been limited by a lack of attention to proper methods of calculating solute clearance by the artificial kidney.", "contents": "Drug kinetics and artificial kidneys. The factors affecting solute movement across the membrane during haemodialysis are well understood. Likewise the mathematics of drug kinetics are well described. However, studies of the effects of artificial kidneys on drug kinetics have often been limited by a lack of attention to proper methods of calculating solute clearance by the artificial kidney."}
{"id": "PMID:22426", "title": "Haemodynamic observations with KO. 1366 (bunitrolol), a new beta-adrenergic blocking agent.", "content": "The haemodynamic effects of a new beta-adrenergic blocking agent KO.1366 (bunitrolol) were assessed in 10 males admitted to hospital for investigation of chest pain. Measurements were made at rest, during atrial pacing at 100 beats/min, and during hand grip exercise, before and afterintravenous administration of KO.1366 at a dosage of 0.05 mg/kg body weight. There was a 12% (p less than 0.01) slowing in resting heart rate and alpha 4% (p less than 0.05) slowing in exercise heart rate after drug administration. Resting left ventricular end diastolic pressure rose by 2.2 mm Hg (p less than 0.01) following the drug, but there was no significant change during pacing or exercise. Left ventricular systolic pressure and its first derivative did not change significantly. Cardiac output rose slightly, and stroke volume at rest and during exercise showed a considerable increase. In the dosage used, KO.1366 has an important chronotropic effect on the heart without causing significant myocardial depression.", "contents": "Haemodynamic observations with KO. 1366 (bunitrolol), a new beta-adrenergic blocking agent. The haemodynamic effects of a new beta-adrenergic blocking agent KO.1366 (bunitrolol) were assessed in 10 males admitted to hospital for investigation of chest pain. Measurements were made at rest, during atrial pacing at 100 beats/min, and during hand grip exercise, before and afterintravenous administration of KO.1366 at a dosage of 0.05 mg/kg body weight. There was a 12% (p less than 0.01) slowing in resting heart rate and alpha 4% (p less than 0.05) slowing in exercise heart rate after drug administration. Resting left ventricular end diastolic pressure rose by 2.2 mm Hg (p less than 0.01) following the drug, but there was no significant change during pacing or exercise. Left ventricular systolic pressure and its first derivative did not change significantly. Cardiac output rose slightly, and stroke volume at rest and during exercise showed a considerable increase. In the dosage used, KO.1366 has an important chronotropic effect on the heart without causing significant myocardial depression."}
{"id": "PMID:22432", "title": "Lack of effect of acid-base alterations on growth hormone secretion in man.", "content": "In order to study the possible effect of acid-base alterations on growth hormone (GH) secretion in man the exercise-induced GH secretion was compared with the tentative GH release resulting from the acidosis due to hyperlactacidemia after the infusion of fructose. Submaximal exercise on bicycle ergometer resulted in a significant increase of plasma GH and lactate and in acid-base alterations. The infusion of 60 g of fructose during 60 min was without effect on plasma GH level in spite of the increase of serum lactate and slight acid-base alterations. It is concluded that no causal relationship may be found between the acid-base alterations and the increase of plasma GH during physical exercise.", "contents": "Lack of effect of acid-base alterations on growth hormone secretion in man. In order to study the possible effect of acid-base alterations on growth hormone (GH) secretion in man the exercise-induced GH secretion was compared with the tentative GH release resulting from the acidosis due to hyperlactacidemia after the infusion of fructose. Submaximal exercise on bicycle ergometer resulted in a significant increase of plasma GH and lactate and in acid-base alterations. The infusion of 60 g of fructose during 60 min was without effect on plasma GH level in spite of the increase of serum lactate and slight acid-base alterations. It is concluded that no causal relationship may be found between the acid-base alterations and the increase of plasma GH during physical exercise."}
{"id": "PMID:22434", "title": "Enzymes of ammonia detoxication after portacaval shunt in the rat. II. Enzymes of glutamate metabolism.", "content": "Besides the synthesis of urea, ammonia detoxication at high concentrations can also be effected through enzyme reactions involved in glutamic acid metabolism. These mechanisms are also operative in extrahepatic tissues. Hyperammonemia is also found in the animal model of the portacaval shunt (PCS) rat. This model was chosen to study the activities of glutamate dehydrogenase, glutamine synthetase and glutaminase I in liver, brain and kidney 10, 20 and 30 days after PCS. In brain and kidney ammonia is detoxified mainly by the glutamate dehydrogenase and glutamine synthetase reactions whereas in the liver these enzyme reactions play a minor role.", "contents": "Enzymes of ammonia detoxication after portacaval shunt in the rat. II. Enzymes of glutamate metabolism. Besides the synthesis of urea, ammonia detoxication at high concentrations can also be effected through enzyme reactions involved in glutamic acid metabolism. These mechanisms are also operative in extrahepatic tissues. Hyperammonemia is also found in the animal model of the portacaval shunt (PCS) rat. This model was chosen to study the activities of glutamate dehydrogenase, glutamine synthetase and glutaminase I in liver, brain and kidney 10, 20 and 30 days after PCS. In brain and kidney ammonia is detoxified mainly by the glutamate dehydrogenase and glutamine synthetase reactions whereas in the liver these enzyme reactions play a minor role."}
{"id": "PMID:22435", "title": "Purification and characterization of two aldehyde dehydrogenases from Pseudomonas aeruginosa.", "content": "Two soluble aldehyde dehydrogenases isoenzymes have been purified and separated from extracts of a paraffin-assimilating bacterium, Pseudomonas aeruginosa. The first one, obtained at an estimated purity of 20% (spec. act. with butanal 0.33 kat/kg) was NAD-dependent. It was rapidly inactivated at pH 8.6 but was efficiently protected by NAD. It had a molecular weight of 225000 and presented a high affinity for aldehydes of short and middle chain lengths. The second enzyme, obtained in a nearly homogenous state (spec. act. with pentanal 0.62 kat/kg) was NADP-dependent. It was activated by ions, in particular potassium ions, and had a good affinity for aldehydes of higher chain lengths. Both enzymes were stabilized by thiols and glycerol and were inactivated by reagents of sulfhydryl groups. These enzymes are 'constitutive' and their physiological function is uncertain. When the bacteria were grown on n-paraffin a new membrane-bound NAD-dependent aldehyde dehydrogenase activity was produced.", "contents": "Purification and characterization of two aldehyde dehydrogenases from Pseudomonas aeruginosa. Two soluble aldehyde dehydrogenases isoenzymes have been purified and separated from extracts of a paraffin-assimilating bacterium, Pseudomonas aeruginosa. The first one, obtained at an estimated purity of 20% (spec. act. with butanal 0.33 kat/kg) was NAD-dependent. It was rapidly inactivated at pH 8.6 but was efficiently protected by NAD. It had a molecular weight of 225000 and presented a high affinity for aldehydes of short and middle chain lengths. The second enzyme, obtained in a nearly homogenous state (spec. act. with pentanal 0.62 kat/kg) was NADP-dependent. It was activated by ions, in particular potassium ions, and had a good affinity for aldehydes of higher chain lengths. Both enzymes were stabilized by thiols and glycerol and were inactivated by reagents of sulfhydryl groups. These enzymes are 'constitutive' and their physiological function is uncertain. When the bacteria were grown on n-paraffin a new membrane-bound NAD-dependent aldehyde dehydrogenase activity was produced."}
{"id": "PMID:22436", "title": "Inhibitory activity of terfenadine on histamine-induced skin wheals in man.", "content": "The inhibitory effect of orally administered terfenadine on the area of histamine-induced skin wheals was studied by single dose and multiple dose trials in 12 normal male volunteers. Single doses of 20, 60 and 200 mg of terfenadine produced dose-dependent decreases in histamine wheal area that reached a maximum by the fourth hour after dosing. The 60 and 200 mg doses blocked almost 90% of histamine whealing, and significant reduction of the wheal area persisted for 8 h. During the multiple dose trial histamine whealing was markedly inhibited after the fifth and sixth dose of terfenadine 20, 40 or 60 mg every 8 h and of 60 mg every 12 h. On the last three dosage schedules inhibition persisted for at least 12 h after the final dose. Inhibition of histamine-induced skin whealing appears to be a quantitative index of the time course of histamine H1-receptor antagonist action.", "contents": "Inhibitory activity of terfenadine on histamine-induced skin wheals in man. The inhibitory effect of orally administered terfenadine on the area of histamine-induced skin wheals was studied by single dose and multiple dose trials in 12 normal male volunteers. Single doses of 20, 60 and 200 mg of terfenadine produced dose-dependent decreases in histamine wheal area that reached a maximum by the fourth hour after dosing. The 60 and 200 mg doses blocked almost 90% of histamine whealing, and significant reduction of the wheal area persisted for 8 h. During the multiple dose trial histamine whealing was markedly inhibited after the fifth and sixth dose of terfenadine 20, 40 or 60 mg every 8 h and of 60 mg every 12 h. On the last three dosage schedules inhibition persisted for at least 12 h after the final dose. Inhibition of histamine-induced skin whealing appears to be a quantitative index of the time course of histamine H1-receptor antagonist action."}
{"id": "PMID:22437", "title": "The effect of diphenhydramine alone and in combination with ethanol on histamine skin response and mental performance.", "content": "The effects of diphenhydramine and diphenhydramine plus ethanol on response to intradermal histamine and on mental performance were assessed in twelve male volunteers. A significant impairment of histamine skin response was found with diphenhydramine. This response was unaffected by ethanol. Ethanol improved performance with a tracking test compared with diphenhydramine alone, the effect was not potentiated by the combination. None of the treatments had a significant effect on a digit symbol substitution test. Co-administration of ethanol and diphenhydramine caused greater impairment of performance in a serial seven subtraction test than diphenhydramine alone. There was no correlation between central and peripheral effects of the antihistamine.", "contents": "The effect of diphenhydramine alone and in combination with ethanol on histamine skin response and mental performance. The effects of diphenhydramine and diphenhydramine plus ethanol on response to intradermal histamine and on mental performance were assessed in twelve male volunteers. A significant impairment of histamine skin response was found with diphenhydramine. This response was unaffected by ethanol. Ethanol improved performance with a tracking test compared with diphenhydramine alone, the effect was not potentiated by the combination. None of the treatments had a significant effect on a digit symbol substitution test. Co-administration of ethanol and diphenhydramine caused greater impairment of performance in a serial seven subtraction test than diphenhydramine alone. There was no correlation between central and peripheral effects of the antihistamine."}
{"id": "PMID:22438", "title": "Double blind study of the effect of glafenine (Glifanan) on oral anticoagulant therapy with phenprocoumon (Marcumar).", "content": "The interaction between phenprocoumon (Marcumar) and glafenine (Glifanan) was investigated in a double blind study of twenty patients receiving long term treatment with phenprocoumon. Thrombotesttime (TT) values had been stable for more than three months before the study. Patients taking glafenine showed a significant increase in TT during the second and third week of the trial (P less than 0.05) compared with the placebo group. tthe increase in TT was not significant in the fourth week. The average concentrations of phenprocoumon were similar in both groups, which suggests that displacement of the drug from binding was not important. Concentrations of clotting factors II, VII and X showed a decrease in all patients at the time of the maximum TT values. A possible explanation for this interaction is discussed, but the mechanism remains uncertain.", "contents": "Double blind study of the effect of glafenine (Glifanan) on oral anticoagulant therapy with phenprocoumon (Marcumar). The interaction between phenprocoumon (Marcumar) and glafenine (Glifanan) was investigated in a double blind study of twenty patients receiving long term treatment with phenprocoumon. Thrombotesttime (TT) values had been stable for more than three months before the study. Patients taking glafenine showed a significant increase in TT during the second and third week of the trial (P less than 0.05) compared with the placebo group. tthe increase in TT was not significant in the fourth week. The average concentrations of phenprocoumon were similar in both groups, which suggests that displacement of the drug from binding was not important. Concentrations of clotting factors II, VII and X showed a decrease in all patients at the time of the maximum TT values. A possible explanation for this interaction is discussed, but the mechanism remains uncertain."}
{"id": "PMID:22439", "title": "Secondary IgG responses to type 3 pneumococcal polysaccharide. III. T cell requirement for development of B memory cells.", "content": "Mice primed with a thymus-dependent form of Type 3 pneumococcal polysaccharide (S3), i.e. S3 coupled to erythrocytes (S3-RBC) produces S3-specific IgG antibody after secondary challenge with S3-RBC. When mice are depleted of T cells by treatment with anti-lymphocyte serum (ALS) at the time of priming, no IgG antibody is produced after secondary challenge. In order to determine the cellular basis for this phenomenon, various combinations of T and/or B cells from ALS-treated or normal primed mice were transferred to irradiated recipients prior to secondary challenge with S3-RBC. The results indicated that T cells were required at the time of priming with S3-RBC in order to (a) prevent the induction of tolerance in S3-specific B cells in mice primed with high doses of S3-RBC, and (b) induced differentiation of IgG-producing B cell precursors to Bgamma memory cells in mice primed with low doses of antigen.", "contents": "Secondary IgG responses to type 3 pneumococcal polysaccharide. III. T cell requirement for development of B memory cells. Mice primed with a thymus-dependent form of Type 3 pneumococcal polysaccharide (S3), i.e. S3 coupled to erythrocytes (S3-RBC) produces S3-specific IgG antibody after secondary challenge with S3-RBC. When mice are depleted of T cells by treatment with anti-lymphocyte serum (ALS) at the time of priming, no IgG antibody is produced after secondary challenge. In order to determine the cellular basis for this phenomenon, various combinations of T and/or B cells from ALS-treated or normal primed mice were transferred to irradiated recipients prior to secondary challenge with S3-RBC. The results indicated that T cells were required at the time of priming with S3-RBC in order to (a) prevent the induction of tolerance in S3-specific B cells in mice primed with high doses of S3-RBC, and (b) induced differentiation of IgG-producing B cell precursors to Bgamma memory cells in mice primed with low doses of antigen."}
{"id": "PMID:22440", "title": "Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs.", "content": "A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For 10 drugs tested for anti-diarrheal potency significant correlation was observed with binding to brain opiate receptors when binding was carried out in sodium-containing medium. These data add support to the hypothesis that stereospecific opiate binding sites are pharmacological receptors which mediate analgesia and anti-diarrheal action. We found that neuroleptics can bind to opiate receptors with affinities in the micromolar range, in agreement with reports by others. The anti-diarrheal compound loperamide exhibits no significant central opiate effects but binds to opiate receptors from brain in vitro with high affinity. Evidency is presented suggesting that the lack of specific analgesic effect is the result of poor penetration through the blood--brain barrier. Our results lend further support to the similarity of opiate receptors in the brain and in the intestinal tract.", "contents": "Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs. A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For 10 drugs tested for anti-diarrheal potency significant correlation was observed with binding to brain opiate receptors when binding was carried out in sodium-containing medium. These data add support to the hypothesis that stereospecific opiate binding sites are pharmacological receptors which mediate analgesia and anti-diarrheal action. We found that neuroleptics can bind to opiate receptors with affinities in the micromolar range, in agreement with reports by others. The anti-diarrheal compound loperamide exhibits no significant central opiate effects but binds to opiate receptors from brain in vitro with high affinity. Evidency is presented suggesting that the lack of specific analgesic effect is the result of poor penetration through the blood--brain barrier. Our results lend further support to the similarity of opiate receptors in the brain and in the intestinal tract."}
{"id": "PMID:22441", "title": "Characterization of the adrenergic activity of carbuterol (SK&F 40383-A).", "content": "Carbuterol is a beta-adrenergic bronchodilator with selectivity for bronchial smooth muscle relative to cardiac and vascular tissues of several species including man. The present studies were undertaken to further characterize its adrenergic profile. In vitro studies demonstrated that carbuterol was a direct acting beta-adrenergic agonist, not dependent on endogenous catecholamine release, and was devoid of alpha-adrenergic agonist activity. The activity of the racemate was shown to reside primarily in the l-enantiomer. Carbuterol inhibited immunologically induced release of histamine and slow reacting substance of anaphylaxis from passively sensitized fragmented rhesus monkey lung and also inhibited passive cutaneous anaphylaxis in rats. The relatively weak stimulant activity of carbuterol on beta1 receptors mediating both rate and force of contraction was confirmed in anesthetized open-chest dogs. In the anesthetized cat, carbuterol was significantly less potent than isoproterenol in decreasing diastolic blood pressure, increasing heart rate, and decreasing the tension and degree of fusion of incomplete tetanic contraction of the soleus muscle.", "contents": "Characterization of the adrenergic activity of carbuterol (SK&F 40383-A). Carbuterol is a beta-adrenergic bronchodilator with selectivity for bronchial smooth muscle relative to cardiac and vascular tissues of several species including man. The present studies were undertaken to further characterize its adrenergic profile. In vitro studies demonstrated that carbuterol was a direct acting beta-adrenergic agonist, not dependent on endogenous catecholamine release, and was devoid of alpha-adrenergic agonist activity. The activity of the racemate was shown to reside primarily in the l-enantiomer. Carbuterol inhibited immunologically induced release of histamine and slow reacting substance of anaphylaxis from passively sensitized fragmented rhesus monkey lung and also inhibited passive cutaneous anaphylaxis in rats. The relatively weak stimulant activity of carbuterol on beta1 receptors mediating both rate and force of contraction was confirmed in anesthetized open-chest dogs. In the anesthetized cat, carbuterol was significantly less potent than isoproterenol in decreasing diastolic blood pressure, increasing heart rate, and decreasing the tension and degree of fusion of incomplete tetanic contraction of the soleus muscle."}
{"id": "PMID:22442", "title": "Transmitter release and adrenergic mechanical responses in the heart: effect of papaverine and imidazole.", "content": "Chronotropic and inotropic responses were elicited in isolated rabbit hearts by stimulation of the sympathetic nerves or by infusion of noradrenaline or adrenaline and the effects of papaverine and imidazole (10(-7)-10(-6) M) on these responses were studied. The outflow of noradrenaline induced by sympathetic nerve stimulation was assayed in the absence and in the presence of papaverine and imidazole (10(-7)-5 X 10(-7) M). Papaverine increased the outflow of transmitter during nerve stimulation by 45% and potentiated both the chronotropic and inotropic responses induced by nerve stimulation and those induced by infusion of catecholamines. Imidazole inhibited the outflow of transmitter during nerve stimulation by 33%. The data indicate that the \"second messenger\" cyclic AMP is active in more than one step in adrenergic neurotransmission and receptor activation in the heart. Furthermore, tissue cyclic AMP seems to be involved not only in the inotropy induced by circulating catecholamines but also in the more \"physiological\" inotropy elicited by sympathetic nerve stimulation.", "contents": "Transmitter release and adrenergic mechanical responses in the heart: effect of papaverine and imidazole. Chronotropic and inotropic responses were elicited in isolated rabbit hearts by stimulation of the sympathetic nerves or by infusion of noradrenaline or adrenaline and the effects of papaverine and imidazole (10(-7)-10(-6) M) on these responses were studied. The outflow of noradrenaline induced by sympathetic nerve stimulation was assayed in the absence and in the presence of papaverine and imidazole (10(-7)-5 X 10(-7) M). Papaverine increased the outflow of transmitter during nerve stimulation by 45% and potentiated both the chronotropic and inotropic responses induced by nerve stimulation and those induced by infusion of catecholamines. Imidazole inhibited the outflow of transmitter during nerve stimulation by 33%. The data indicate that the \"second messenger\" cyclic AMP is active in more than one step in adrenergic neurotransmission and receptor activation in the heart. Furthermore, tissue cyclic AMP seems to be involved not only in the inotropy induced by circulating catecholamines but also in the more \"physiological\" inotropy elicited by sympathetic nerve stimulation."}
{"id": "PMID:22443", "title": "Plasma cyclic GMP: response to cholinergic agents.", "content": "S.c. injections of cholinergic agents, carbachol, methacholine and bethanechol, into fasted rats caused rapid increases in the plasma concentration of cyclic GMP, with a sharp peak at 5--10 min after the injection. Acetylcholine gave rise to a rapid accumulation of cyclic GMP in plasma only when administered together with physostigmine which produced only a slight, if any, potentiation of the action of the cholinesterase-resistant choline esters. Cyclic AMP also increased after these drugs, but only subsequently to the rise of cyclic GMP; the primary action of the cholinergic drugs appeared to be the increase in cyclic GMP. Atropine was effective not only in abolishing the increase in plasma cyclic GMP induced by cholinergic drugs but also in lowering the baseline level of cyclic GMP. It was concluded that the plasma concentration of cyclic GMP could serve as a good parameter of cholinergic activity in rats.", "contents": "Plasma cyclic GMP: response to cholinergic agents. S.c. injections of cholinergic agents, carbachol, methacholine and bethanechol, into fasted rats caused rapid increases in the plasma concentration of cyclic GMP, with a sharp peak at 5--10 min after the injection. Acetylcholine gave rise to a rapid accumulation of cyclic GMP in plasma only when administered together with physostigmine which produced only a slight, if any, potentiation of the action of the cholinesterase-resistant choline esters. Cyclic AMP also increased after these drugs, but only subsequently to the rise of cyclic GMP; the primary action of the cholinergic drugs appeared to be the increase in cyclic GMP. Atropine was effective not only in abolishing the increase in plasma cyclic GMP induced by cholinergic drugs but also in lowering the baseline level of cyclic GMP. It was concluded that the plasma concentration of cyclic GMP could serve as a good parameter of cholinergic activity in rats."}
{"id": "PMID:22444", "title": "Narcotic cueing properties of intraventricularly administered sufentanil, fentanyl, morphine and met-enkephalin.", "content": "The narcotic cueing activity of sufentanil, fentanyl, morphine and met-enkephalin was studied upon their injection into the lateral brain ventricle of the rat. Comparative studies on the analgesic activity of the three narcotics support a close correlation between the narcotic cueing and the analgesic activity of narcotic drugs.", "contents": "Narcotic cueing properties of intraventricularly administered sufentanil, fentanyl, morphine and met-enkephalin. The narcotic cueing activity of sufentanil, fentanyl, morphine and met-enkephalin was studied upon their injection into the lateral brain ventricle of the rat. Comparative studies on the analgesic activity of the three narcotics support a close correlation between the narcotic cueing and the analgesic activity of narcotic drugs."}
{"id": "PMID:22451", "title": "Tritiated thymidine incorporation and cell-mediated lympholysis as correlates of acute graft-versus-host reaction.", "content": "The graft-versus-host (GVH) reaction remains a serious consequence of administration of allogeneic immunocompetent cells to an immunosuppressed host even if donors and recipients are matched for major histocompatibility loci. This report describes a murine model for acute GVH reactions. Spleen cells from C3H/He (H-2k) mice, after intravenous injection of BALB/c (H-2d) spleen cells, were specifically cytotoxic for C3H target cells in vitro 4 days after irradiation and reconstitution. The cells in the recipients apparently are of donor genotype. The spleen cells exhibited rapid proliferation in vitro as measured by the uptake of 3H-TdR. The in vitro proliferation was distinguished from erythropoiesis by an assay of 59Fe incorporation. The kinetics of the in vitro incorporation of 3H-TdR and the in vivo uptake of 59Fe are reported.", "contents": "Tritiated thymidine incorporation and cell-mediated lympholysis as correlates of acute graft-versus-host reaction. The graft-versus-host (GVH) reaction remains a serious consequence of administration of allogeneic immunocompetent cells to an immunosuppressed host even if donors and recipients are matched for major histocompatibility loci. This report describes a murine model for acute GVH reactions. Spleen cells from C3H/He (H-2k) mice, after intravenous injection of BALB/c (H-2d) spleen cells, were specifically cytotoxic for C3H target cells in vitro 4 days after irradiation and reconstitution. The cells in the recipients apparently are of donor genotype. The spleen cells exhibited rapid proliferation in vitro as measured by the uptake of 3H-TdR. The in vitro proliferation was distinguished from erythropoiesis by an assay of 59Fe incorporation. The kinetics of the in vitro incorporation of 3H-TdR and the in vivo uptake of 59Fe are reported."}
{"id": "PMID:22455", "title": "Oxatomide, a new orally active drug which inhibits both the release and the effects of allergic mediators.", "content": "Oxatomide is a new potent inhibitor of anaphylactic and allergic reactions. After oral administration, the compound both inhibits the release of endogenous histamine and prevents the effects of exogensous histamine, at comparable doses. The combination of these effects appears to be the basis of the effectiveness of oxatomide in allergic reactions and may lead to clinical application different from classical antihistaminics and from cromoglycate.", "contents": "Oxatomide, a new orally active drug which inhibits both the release and the effects of allergic mediators. Oxatomide is a new potent inhibitor of anaphylactic and allergic reactions. After oral administration, the compound both inhibits the release of endogenous histamine and prevents the effects of exogensous histamine, at comparable doses. The combination of these effects appears to be the basis of the effectiveness of oxatomide in allergic reactions and may lead to clinical application different from classical antihistaminics and from cromoglycate."}
{"id": "PMID:22463", "title": "The effect of temperature on sperm motility and viability.", "content": "Semen specimens from fertile prevasectomy patients maintained at 4 degrees, 20 degrees, and 37 degrees C were evaluated at 3, 6, 12, and 18 hours after collection. Sperm viability, assessed by eosin-nigrosin stain, and motility decreased with time at 20 degrees and 37 degrees C, but at a significantly higher rate at 37 degrees C (where the motility was halved by 12 hours). The slope of the decrease in viability closely paralleled that of the motility except at 4 degrees C, where motility was nearly absent at 6 hours but viability was retained through 18 hours. Bacterial counts rose markedly and the pH fell at 37 degrees C, which may explain the decrease in motility and viability. It is clear from this study that semen should be kept at room temperature (20 degrees C) and not at 37 degrees C if there is to be any delay in its analysis, or a falsely lowered motility will result.", "contents": "The effect of temperature on sperm motility and viability. Semen specimens from fertile prevasectomy patients maintained at 4 degrees, 20 degrees, and 37 degrees C were evaluated at 3, 6, 12, and 18 hours after collection. Sperm viability, assessed by eosin-nigrosin stain, and motility decreased with time at 20 degrees and 37 degrees C, but at a significantly higher rate at 37 degrees C (where the motility was halved by 12 hours). The slope of the decrease in viability closely paralleled that of the motility except at 4 degrees C, where motility was nearly absent at 6 hours but viability was retained through 18 hours. Bacterial counts rose markedly and the pH fell at 37 degrees C, which may explain the decrease in motility and viability. It is clear from this study that semen should be kept at room temperature (20 degrees C) and not at 37 degrees C if there is to be any delay in its analysis, or a falsely lowered motility will result."}
{"id": "PMID:22466", "title": "[The renin-aldosterone system in essential hypertension--hypotensive action of beta adrenergic blocking agents and variation of the renin-aldosterone system (author's transl)].", "content": "The effect of beta adrenergic blocking agents on the renin release from the kidney and its possible role in the hypotensive effect of these agents were studied in patients with essential hypertension. Oxprenolol induced a significant decrease in systolic blood pressure and PRA, but the correlation between the decrease in blood pressure and the decrease in PRA was not found. When the effect of carteolol, another beta adrenergic blocking agent, was studied, a decrease in blood pressure was obtained, but there was a rise in PRA. These observations suggest that the hypotensive action of beta adrenergic blocking agents does not result from their effects on PRA.", "contents": "[The renin-aldosterone system in essential hypertension--hypotensive action of beta adrenergic blocking agents and variation of the renin-aldosterone system (author's transl)]. The effect of beta adrenergic blocking agents on the renin release from the kidney and its possible role in the hypotensive effect of these agents were studied in patients with essential hypertension. Oxprenolol induced a significant decrease in systolic blood pressure and PRA, but the correlation between the decrease in blood pressure and the decrease in PRA was not found. When the effect of carteolol, another beta adrenergic blocking agent, was studied, a decrease in blood pressure was obtained, but there was a rise in PRA. These observations suggest that the hypotensive action of beta adrenergic blocking agents does not result from their effects on PRA."}
{"id": "PMID:22468", "title": "pH effect on the percutaneous penetration of lignocaine hydrochloride.", "content": "(1) The percutaneous penetration of lignocaine hydrochloride is affected in vitro by the pH; alkalinity increased the portion of the unionized drug which permeated through the lipoid outer skin membrane of guinea pigs. (2) The amount of lignocaine accumulated on the dermal side of the diffusion cell containing isotonic phosphate buffer (pH 7.4) was directly proportional to the initial concentration of the applied drug at the alkaline pH. (3) The dermal transfer rates of lignocaine into the isotonic phosphate buffer (pH 7.4) of the diffusion cell decreased with the increase in the pH of the initially applied solution on the epidermal side of the diffusion cell; the simultaneous cutaneous penetration of the alkaline buffer promoted retention of the unionized drug in the dermis. (4) Percutaneous penetration of lignocaine hydrochloride represents a dual-stage process involving dissimilar rates of clearance into cutaneous tissue and transfer from dermis to body fluids. Variations in the alkaline pH of lignocaine hydrochloride solution appear to govern the rate-limiting factor of the total percutaneous penetration; the pharmacologic action of lignocaine may thus be localized.", "contents": "pH effect on the percutaneous penetration of lignocaine hydrochloride. (1) The percutaneous penetration of lignocaine hydrochloride is affected in vitro by the pH; alkalinity increased the portion of the unionized drug which permeated through the lipoid outer skin membrane of guinea pigs. (2) The amount of lignocaine accumulated on the dermal side of the diffusion cell containing isotonic phosphate buffer (pH 7.4) was directly proportional to the initial concentration of the applied drug at the alkaline pH. (3) The dermal transfer rates of lignocaine into the isotonic phosphate buffer (pH 7.4) of the diffusion cell decreased with the increase in the pH of the initially applied solution on the epidermal side of the diffusion cell; the simultaneous cutaneous penetration of the alkaline buffer promoted retention of the unionized drug in the dermis. (4) Percutaneous penetration of lignocaine hydrochloride represents a dual-stage process involving dissimilar rates of clearance into cutaneous tissue and transfer from dermis to body fluids. Variations in the alkaline pH of lignocaine hydrochloride solution appear to govern the rate-limiting factor of the total percutaneous penetration; the pharmacologic action of lignocaine may thus be localized."}
{"id": "PMID:22470", "title": "Biological and immunological characterization of human luteinizing hormone: I. Biological profile in pituitary and plasma samples after electrofocusing.", "content": "Pituitary and plasma pools from postmenopausal women and plasma pools from women at midcycle were fractionated by electrofocusing in sucrose density gradients. The biological LH activity was determined in each of the electrofocusing fractions by the use of an in vitro bioassay method. A heterogeneous profile of LH activity was found in both pituitary and plasma samples with a large proportion present within the pH range 6.5-10. In a total of 11 electrofocusing runs 7 main regions of high LH activity were found within this range with mean pI values (+/- SD) of 6.75 +/- 0.08 (n = 6), 7.33 +/- 0.08 (11), 7.80 +/- 0.09 (11), 8.23 +/- 0.10 (11), 8.81 +/- 0.04 (7), 9.17 +/- 0.05 (6) and 9.55 (2). A significantly higher proportion of LH activity was found in the midcycle plasma samples (36%) in the pH regions with mean pI values of 8.81, 9.17 and 9.55 than in postmenopausal plasma (7%) and pituitary extracts (5%). This indicates that the profile of biologically active LH in women in the fertile age is different from that present in postmenopausal women. By detailed fractionation based on narrow pH range studies and the refocusing of specific peak fractions it was shown that each of the regions studied consisted of several peaks of LH activity indicating the presence of a large number of molecular species exhibiting varying degrees of LH activity. The relative proportions of these species showed considerable differences between sources but also between samples from the same source.", "contents": "Biological and immunological characterization of human luteinizing hormone: I. Biological profile in pituitary and plasma samples after electrofocusing. Pituitary and plasma pools from postmenopausal women and plasma pools from women at midcycle were fractionated by electrofocusing in sucrose density gradients. The biological LH activity was determined in each of the electrofocusing fractions by the use of an in vitro bioassay method. A heterogeneous profile of LH activity was found in both pituitary and plasma samples with a large proportion present within the pH range 6.5-10. In a total of 11 electrofocusing runs 7 main regions of high LH activity were found within this range with mean pI values (+/- SD) of 6.75 +/- 0.08 (n = 6), 7.33 +/- 0.08 (11), 7.80 +/- 0.09 (11), 8.23 +/- 0.10 (11), 8.81 +/- 0.04 (7), 9.17 +/- 0.05 (6) and 9.55 (2). A significantly higher proportion of LH activity was found in the midcycle plasma samples (36%) in the pH regions with mean pI values of 8.81, 9.17 and 9.55 than in postmenopausal plasma (7%) and pituitary extracts (5%). This indicates that the profile of biologically active LH in women in the fertile age is different from that present in postmenopausal women. By detailed fractionation based on narrow pH range studies and the refocusing of specific peak fractions it was shown that each of the regions studied consisted of several peaks of LH activity indicating the presence of a large number of molecular species exhibiting varying degrees of LH activity. The relative proportions of these species showed considerable differences between sources but also between samples from the same source."}
{"id": "PMID:22472", "title": "Comparative studies on the metabolism of 2-(tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil.", "content": "5=Fluorouracil inhibited DNA synthesis markedly using various DNA precursors such as deoxyuridine, orotic acid, uracil, and uridine except for thymidine. 2-(Tetrahydrofury)-5-fluorouracil (FT-207) did not inhibit DNA synthesis with any of the precursors tested. The metabolisms of 5-fluorouracil and FT-207 in mice and rats were studied. When administered intravenously 5-fluorouracil was rapidly degraded to fluoro-beta-alanine in both mice and rats, while at most 70% of FT-207 was slowly degraded after a prolonged period. The metabolites of FT-207 were found to be 5-fluorouracil and fluoro-beta-alanine in both species of animals. In vitro degradation of FT-207 into 5-fluorouracil was observed mainly in the microsomal fraction in the presence of NADPH. This result suggested that microsomal electron-transport system was concerned with the degradation of FT-207.", "contents": "Comparative studies on the metabolism of 2-(tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil. 5=Fluorouracil inhibited DNA synthesis markedly using various DNA precursors such as deoxyuridine, orotic acid, uracil, and uridine except for thymidine. 2-(Tetrahydrofury)-5-fluorouracil (FT-207) did not inhibit DNA synthesis with any of the precursors tested. The metabolisms of 5-fluorouracil and FT-207 in mice and rats were studied. When administered intravenously 5-fluorouracil was rapidly degraded to fluoro-beta-alanine in both mice and rats, while at most 70% of FT-207 was slowly degraded after a prolonged period. The metabolites of FT-207 were found to be 5-fluorouracil and fluoro-beta-alanine in both species of animals. In vitro degradation of FT-207 into 5-fluorouracil was observed mainly in the microsomal fraction in the presence of NADPH. This result suggested that microsomal electron-transport system was concerned with the degradation of FT-207."}
{"id": "PMID:22473", "title": "Electron spin resonance study on the mode of generation of free radicals of daunomycin, adriamycin, and carboquone in NAD(P)H-microsome system.", "content": "The mode of generation of free radicals of daunomycin, adriamycin, and carboquone in the NADPH-rat liver microsome system was studied at room temperature by electron spin resonance (ESR) spectroscopy. ESR signals of all these quinoid anticancer chemicals were detected when dissolved oxygen in the reaction mixture was consumed since the radicals are easilyaut oxidizable. All the radicals had an appreciable lifetime under anaerobic conditions. However, there were differences in the mode of their generation between daunomycin and adriamycin, on the one hand, and carboquone, on the other, with respect to the lag time and the effect of the amount of chemicals, pH of the medium, kind of electron donors, NADPH and NADH, and the presence of excess of DNA. Especially, ESR signal reappeared after the first signal had decreased considerably, in the case of daunomycin and adriamycin but not in carboquone. Intact Ehrlich ascites tumor cells also gave rise to an ESR signal of adriamycin and carboquone, but the former signal was prevented from appearing in the presence of glucose.", "contents": "Electron spin resonance study on the mode of generation of free radicals of daunomycin, adriamycin, and carboquone in NAD(P)H-microsome system. The mode of generation of free radicals of daunomycin, adriamycin, and carboquone in the NADPH-rat liver microsome system was studied at room temperature by electron spin resonance (ESR) spectroscopy. ESR signals of all these quinoid anticancer chemicals were detected when dissolved oxygen in the reaction mixture was consumed since the radicals are easilyaut oxidizable. All the radicals had an appreciable lifetime under anaerobic conditions. However, there were differences in the mode of their generation between daunomycin and adriamycin, on the one hand, and carboquone, on the other, with respect to the lag time and the effect of the amount of chemicals, pH of the medium, kind of electron donors, NADPH and NADH, and the presence of excess of DNA. Especially, ESR signal reappeared after the first signal had decreased considerably, in the case of daunomycin and adriamycin but not in carboquone. Intact Ehrlich ascites tumor cells also gave rise to an ESR signal of adriamycin and carboquone, but the former signal was prevented from appearing in the presence of glucose."}
{"id": "PMID:22474", "title": "Establishment of a clonal strain of hepatoma cells derived from Morris hepatoma 8999.", "content": "A new line of tissue culture cells derived from a slow-growing hepatoma 8999 was established and named 8999C. The isolation method, growth pattern, and morphology of the 8999C cells are described. Several hepatic enzyme activities in 8999C cells were compared to those in the original hepatoma 8999. The ornithine aminotransferase (EC 2.6.1.13), tyrosine aminotransferase (EC 2.6.1.5), and arginase (EC 3.5.3.1) activities in the 8999C cells were one-third, one-tenth, and one-hundredth of those of the respective activities in the original hepatoma 8999, and mitochondrial serine protease, which has much higher activity in hepatoma 8999 than in normal liver cells, was not detected in 8999C cells. Tyrosine aminotransferase in 8999C cells was induced by dexamethasone but not by N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate or insulin. Unlike in hepatoma 8999, glucocorticoid did not induce arginase in 8999C cells.", "contents": "Establishment of a clonal strain of hepatoma cells derived from Morris hepatoma 8999. A new line of tissue culture cells derived from a slow-growing hepatoma 8999 was established and named 8999C. The isolation method, growth pattern, and morphology of the 8999C cells are described. Several hepatic enzyme activities in 8999C cells were compared to those in the original hepatoma 8999. The ornithine aminotransferase (EC 2.6.1.13), tyrosine aminotransferase (EC 2.6.1.5), and arginase (EC 3.5.3.1) activities in the 8999C cells were one-third, one-tenth, and one-hundredth of those of the respective activities in the original hepatoma 8999, and mitochondrial serine protease, which has much higher activity in hepatoma 8999 than in normal liver cells, was not detected in 8999C cells. Tyrosine aminotransferase in 8999C cells was induced by dexamethasone but not by N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate or insulin. Unlike in hepatoma 8999, glucocorticoid did not induce arginase in 8999C cells."}
{"id": "PMID:22471", "title": "Problems related to the use of serum and trypsin in the growth of monkey kidney cells.", "content": "A function of serum in the growth medium for primary monkey kidney cells has been shown to be inhibition of proteolytic enzymes. Serum inactivates the residual trypsin remaining from enzymatic digestion of the kidneys and the proteolytic enzymes subsequently synthesized by the cells. Freshly trypsinized cells could be grown to monolayers in the absence of serum provided that they were repeatedly washed to remove residual trypsin. In the absence of serum, cell growth ceased on the 4-5th day after initiation of the culture, at which time the culture fluids became active proteolytically. When the 5th day fluids were replaced with fresh serum-free medium, cell growth was accelerated and a monolayer was attained by the 7th day. If cells were grown in the absence of whole serum but in the presence of medium containing alpha globulins or fetuin which inhibit both trypsin and cell proteases, such cultures grew as well as cultures containing serum. The sterilization of trypsin for use in digestion of tissues and cell cultures poses a serious problem. After filtration through 0.22 micron filters, trypsin preparations may still contain adventitious viruses, mycoplasma and minute forms of pseudomonas and other bacteria or bacteria-produced toxins, which pass the membrane pores. A process of purifying and sterilizing trypsin without deleteriously affecting its proteolytic activity is described.", "contents": "Problems related to the use of serum and trypsin in the growth of monkey kidney cells. A function of serum in the growth medium for primary monkey kidney cells has been shown to be inhibition of proteolytic enzymes. Serum inactivates the residual trypsin remaining from enzymatic digestion of the kidneys and the proteolytic enzymes subsequently synthesized by the cells. Freshly trypsinized cells could be grown to monolayers in the absence of serum provided that they were repeatedly washed to remove residual trypsin. In the absence of serum, cell growth ceased on the 4-5th day after initiation of the culture, at which time the culture fluids became active proteolytically. When the 5th day fluids were replaced with fresh serum-free medium, cell growth was accelerated and a monolayer was attained by the 7th day. If cells were grown in the absence of whole serum but in the presence of medium containing alpha globulins or fetuin which inhibit both trypsin and cell proteases, such cultures grew as well as cultures containing serum. The sterilization of trypsin for use in digestion of tissues and cell cultures poses a serious problem. After filtration through 0.22 micron filters, trypsin preparations may still contain adventitious viruses, mycoplasma and minute forms of pseudomonas and other bacteria or bacteria-produced toxins, which pass the membrane pores. A process of purifying and sterilizing trypsin without deleteriously affecting its proteolytic activity is described."}
{"id": "PMID:22478", "title": "Specificity of cleavage by restriction nuclease from Bacillus subtilis.", "content": "The restriction nuclease from B. subtilis (Bsu) which cleaves in the middle of the tetra-nucleotide sequence 5'-GGCC-3' 3'-CCGG-5' has been found to decrease its substrate specificity at high nuclease concentrations. There are special conditions, high pH, low ionic strength, and high glycerol content, which strongly enhance splitting with decreased specificity and also lead to splitting of single-stranded DNA. By sequence analyses it is shown that the reduction in specificity of Bsu corresponds to cleavage predominantly at 5'-GC-3' 3'-CG-5' sequences. No comparable change in specificity has been observed in a restriction nuclease from Haemophilus aegyptius (HaeIII), and isoschizomer of Bsu.", "contents": "Specificity of cleavage by restriction nuclease from Bacillus subtilis. The restriction nuclease from B. subtilis (Bsu) which cleaves in the middle of the tetra-nucleotide sequence 5'-GGCC-3' 3'-CCGG-5' has been found to decrease its substrate specificity at high nuclease concentrations. There are special conditions, high pH, low ionic strength, and high glycerol content, which strongly enhance splitting with decreased specificity and also lead to splitting of single-stranded DNA. By sequence analyses it is shown that the reduction in specificity of Bsu corresponds to cleavage predominantly at 5'-GC-3' 3'-CG-5' sequences. No comparable change in specificity has been observed in a restriction nuclease from Haemophilus aegyptius (HaeIII), and isoschizomer of Bsu."}
{"id": "PMID:22479", "title": "Effects of dihydroergotoxine mesylate on aging neurons in vitro.", "content": "C1300 mouse neuroblastoma cells gradually accumulate lipofuscin-like pigment when they are maintained in culture. Pigment was demonstrated by positive straining for acid phosphatase and with periodic acid-Schiff stain. Pigment was formation in cells was reduced by exposure of the cells to lower doses of dihydroergotoxine mesylate which also induced neurite formation and increased protein synthesis. Since lipofuscin appears to originate as a result of wear and tear within the cells, the drug probably exerts its beneficial effects by reducing the rate of intracellular wear and tear associated with aging.", "contents": "Effects of dihydroergotoxine mesylate on aging neurons in vitro. C1300 mouse neuroblastoma cells gradually accumulate lipofuscin-like pigment when they are maintained in culture. Pigment was demonstrated by positive straining for acid phosphatase and with periodic acid-Schiff stain. Pigment was formation in cells was reduced by exposure of the cells to lower doses of dihydroergotoxine mesylate which also induced neurite formation and increased protein synthesis. Since lipofuscin appears to originate as a result of wear and tear within the cells, the drug probably exerts its beneficial effects by reducing the rate of intracellular wear and tear associated with aging."}
{"id": "PMID:22480", "title": "Binding interactions of ergot alkaloids with monoaminergic receptors in the brain.", "content": "The interactions of ergot alkaloids and of other drugs with dopamine (DA) and alpha-adrenergic receptors were investigated. The tested ergot alkaloids inhibit synaptosomal tyrosine hydroxylase activity and reverse the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. Thus, ergot alkaloids interact as both agonists and antagonists with the presynaptic DA receptors. Ergot alkaloids also compete effectively for the binding of 3H-DA and 3H-haloperidol to bovine striatal membranes. These results show that these drugs are mixed agonist-antagonists with respect to the postsynaptic DA receptors. To determine the effects of ergot alkaloids and of neuroleptics on the alpha-adrenergic receptors in the CNS, we have measured their effects on the binding of 3H-dihydroergocryptine and 3H-WB-4101 to cerebral cortical membranes. The displacing potencies of the tested ergot alkaloids and of the neuroleptics indicated that they have a high affinity for the alpha-adrenoreceptors in the CNS. The mechanisms underlying the therapeutic efficacy of mixed agonist-antigonists of DA and alpha-adrenergic receptors in Parkinson's disease and in geriatric disorders were considered.", "contents": "Binding interactions of ergot alkaloids with monoaminergic receptors in the brain. The interactions of ergot alkaloids and of other drugs with dopamine (DA) and alpha-adrenergic receptors were investigated. The tested ergot alkaloids inhibit synaptosomal tyrosine hydroxylase activity and reverse the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. Thus, ergot alkaloids interact as both agonists and antagonists with the presynaptic DA receptors. Ergot alkaloids also compete effectively for the binding of 3H-DA and 3H-haloperidol to bovine striatal membranes. These results show that these drugs are mixed agonist-antagonists with respect to the postsynaptic DA receptors. To determine the effects of ergot alkaloids and of neuroleptics on the alpha-adrenergic receptors in the CNS, we have measured their effects on the binding of 3H-dihydroergocryptine and 3H-WB-4101 to cerebral cortical membranes. The displacing potencies of the tested ergot alkaloids and of the neuroleptics indicated that they have a high affinity for the alpha-adrenoreceptors in the CNS. The mechanisms underlying the therapeutic efficacy of mixed agonist-antigonists of DA and alpha-adrenergic receptors in Parkinson's disease and in geriatric disorders were considered."}
{"id": "PMID:22481", "title": "[Acute myocardial infarct without pathological CK-MB isoenzyme activities].", "content": "Serum CK-MB is regarded as a specific indicator for myocardial diseases. Total CK and the isoenzyme CK-MB were measured in 69 patients with myocardial infarction. In 5 of the cases no pathological CK-MB-activities have been seen. Nevertheless, the clinical importance of CK-MB determination as a differential diagnostic aid remains.", "contents": "[Acute myocardial infarct without pathological CK-MB isoenzyme activities]. Serum CK-MB is regarded as a specific indicator for myocardial diseases. Total CK and the isoenzyme CK-MB were measured in 69 patients with myocardial infarction. In 5 of the cases no pathological CK-MB-activities have been seen. Nevertheless, the clinical importance of CK-MB determination as a differential diagnostic aid remains."}
{"id": "PMID:22483", "title": "Effects of culture milieus on the development of mouse blastocysts in vitro.", "content": "Various culture milieus were examined for their support of mouse blastocyst development. Two important variables were the time at which human cord serum was added to the medium and the concentration of amino acids. In the best medium. Eagle's Minimum Essential Medium (fortified with six times the usual amino-acid concentration plus 20 percent fetal bovine serum, replaced after 48 hr with human cord serum), 83 percent of the blastocysts shed the zona pellucida, 58 percent developed to the early egg cylinder stage, 42 percent to the advanced egg cylinder stage and 22 percent attained the primitive streak stage after 6 to 8 days of culture.", "contents": "Effects of culture milieus on the development of mouse blastocysts in vitro. Various culture milieus were examined for their support of mouse blastocyst development. Two important variables were the time at which human cord serum was added to the medium and the concentration of amino acids. In the best medium. Eagle's Minimum Essential Medium (fortified with six times the usual amino-acid concentration plus 20 percent fetal bovine serum, replaced after 48 hr with human cord serum), 83 percent of the blastocysts shed the zona pellucida, 58 percent developed to the early egg cylinder stage, 42 percent to the advanced egg cylinder stage and 22 percent attained the primitive streak stage after 6 to 8 days of culture."}
{"id": "PMID:22486", "title": "Demonstration and characterization of a serum factor produced by activated T cells.", "content": "Spleen rosette forming cells (RFC) from adult thymectomized mice have a low sensitivity to inhibition by anitheta serum (AOS) and azathioprine (AZ) in comparison with normal spleen or thymus RFC. Thymus extracts and normal mouse serum (but not spleen extracts or thymectomized mouse serum) correct this abnormality after a 30 min in vitro incubation with spleen cells. We report here the existence of a serum factor produced in allogeneic reactions with the same activity on rosettes as thymic factor (TF). This 'allogeneic' factor (AF) is detectable in mice undergoing a graft versus host reaction (GVHR), rejecting skin allografts or allogeneic cells or responding to thymus-dependent antigens such as heterologous red blood cells or BSA. The T-cell origin of AF is indicated by AF presence in nude mice submitted to the same allogeneic stimuli as listed above and in normal mice injected with PVP or LPS. AF is distinct from the thymic factor as shown by differences in electric charge. Moreover, in contrast with TF there is no specific high molecular weight inhibitor of AF. Preliminary biochemical studies indicate that AF is probably a peptide of low molecular weight (greater than 5000 daltons). Its target cell is probably a T-cell precursor.", "contents": "Demonstration and characterization of a serum factor produced by activated T cells. Spleen rosette forming cells (RFC) from adult thymectomized mice have a low sensitivity to inhibition by anitheta serum (AOS) and azathioprine (AZ) in comparison with normal spleen or thymus RFC. Thymus extracts and normal mouse serum (but not spleen extracts or thymectomized mouse serum) correct this abnormality after a 30 min in vitro incubation with spleen cells. We report here the existence of a serum factor produced in allogeneic reactions with the same activity on rosettes as thymic factor (TF). This 'allogeneic' factor (AF) is detectable in mice undergoing a graft versus host reaction (GVHR), rejecting skin allografts or allogeneic cells or responding to thymus-dependent antigens such as heterologous red blood cells or BSA. The T-cell origin of AF is indicated by AF presence in nude mice submitted to the same allogeneic stimuli as listed above and in normal mice injected with PVP or LPS. AF is distinct from the thymic factor as shown by differences in electric charge. Moreover, in contrast with TF there is no specific high molecular weight inhibitor of AF. Preliminary biochemical studies indicate that AF is probably a peptide of low molecular weight (greater than 5000 daltons). Its target cell is probably a T-cell precursor."}
{"id": "PMID:22488", "title": "Changes in the microflora and physiology of the anterior intestinal tract of pigs weaned at 2 days, with special reference to the pathogenesis of diarrhea.", "content": "The gastrointestinal microflora and gastric physiology of piglets weaned at 2 days was compared with that of piglets allowed to continue sucking the sow. Although there was a significantly higher count of Escherichia coli in the stomach, duodenum, and jejunum of the early-weaned compared with sow-reared pigs, these differences were not detectable in samples from the ileum. There were no quantitative differences in lactobacilli and in streptococci between the two treatments. Lactobacillus fermentum, L. acidophilus, Streptococcus salivarius, S. bovis, and related biotypes were isolated from both groups of pigs. L. fermentum and S. salivarius were isolated more frequently from sow-reared piglets. The weight of digesta in the stomach was greater in weaned than in sucking pigs and was even greater in scouring weaned pigs, suggesting that in scouring pigs there may be gastric stasis. The gastric pH was higher in the weaned pigs at 4 days of age, but gradually decreased up to 10 days, during which time the lactic acid concentration rose. In weaned pigs there was a highly significant negative correlation between pH and lactic acid concentration in the stomach digesta, and also a positive correlation between pH and number of E. coli. These correlations suggest that lactic acid, from bacterial fermentation, is the major component in the regulation of gastric pH in weaned pigs. Three of twenty sucking pigs, but none of the weaned pigs, were secreting HCl (chloride concentration > 3 mg/g, pH < 3.5). In sucking pigs there was an inverse relationship between the chloride and lactic acid concentrations in the digesta. In weaned scouring pigs there was a nonsignificant increase in pepsin concentration in the stomach tissue. There was a threefold increase in the total proteolytic activity of the stomach tissue.", "contents": "Changes in the microflora and physiology of the anterior intestinal tract of pigs weaned at 2 days, with special reference to the pathogenesis of diarrhea. The gastrointestinal microflora and gastric physiology of piglets weaned at 2 days was compared with that of piglets allowed to continue sucking the sow. Although there was a significantly higher count of Escherichia coli in the stomach, duodenum, and jejunum of the early-weaned compared with sow-reared pigs, these differences were not detectable in samples from the ileum. There were no quantitative differences in lactobacilli and in streptococci between the two treatments. Lactobacillus fermentum, L. acidophilus, Streptococcus salivarius, S. bovis, and related biotypes were isolated from both groups of pigs. L. fermentum and S. salivarius were isolated more frequently from sow-reared piglets. The weight of digesta in the stomach was greater in weaned than in sucking pigs and was even greater in scouring weaned pigs, suggesting that in scouring pigs there may be gastric stasis. The gastric pH was higher in the weaned pigs at 4 days of age, but gradually decreased up to 10 days, during which time the lactic acid concentration rose. In weaned pigs there was a highly significant negative correlation between pH and lactic acid concentration in the stomach digesta, and also a positive correlation between pH and number of E. coli. These correlations suggest that lactic acid, from bacterial fermentation, is the major component in the regulation of gastric pH in weaned pigs. Three of twenty sucking pigs, but none of the weaned pigs, were secreting HCl (chloride concentration > 3 mg/g, pH < 3.5). In sucking pigs there was an inverse relationship between the chloride and lactic acid concentrations in the digesta. In weaned scouring pigs there was a nonsignificant increase in pepsin concentration in the stomach tissue. There was a threefold increase in the total proteolytic activity of the stomach tissue."}
{"id": "PMID:22489", "title": "Complement-fixing antibody response in pneumococcal pneumonia.", "content": "Previous studies of complement-fixing antibodies to pneumococcal capsular polysaccharides in humans have yielded conflicting results. We studied 65 sera from 25 patients with pneumococcal pneumonia, using both fresh sera and heat-inactivated sera with added human complement. Only 4 of the 25 patients developed detectable levels of complement-fixing anticapsular antibody. Of the 25 patients, 22 developed detectable levels of hemagglutinating anticapsular antibody, indicating that they were able to develop an immunological response during the infection. Most of the antibody detected by hemagglutination was sensitive to 2-mercaptoethanol, but some 2-mercaptoethanol-resistant antibody was also detected. In studies with rabbit antiserum, the complement fixation test was found to be as sensitive as the hemagglutination test for detection of anticapsular antibody. It is not clear why detectable levels of complement-fixing antibody do not develop more often in patients with pneumococcal pneumonia. Studies of purified anticapsular antibody would be of interest to determine whether or not these antibodies are restricted to immunoglobulin subclasses having a limited capacity to fix complement.", "contents": "Complement-fixing antibody response in pneumococcal pneumonia. Previous studies of complement-fixing antibodies to pneumococcal capsular polysaccharides in humans have yielded conflicting results. We studied 65 sera from 25 patients with pneumococcal pneumonia, using both fresh sera and heat-inactivated sera with added human complement. Only 4 of the 25 patients developed detectable levels of complement-fixing anticapsular antibody. Of the 25 patients, 22 developed detectable levels of hemagglutinating anticapsular antibody, indicating that they were able to develop an immunological response during the infection. Most of the antibody detected by hemagglutination was sensitive to 2-mercaptoethanol, but some 2-mercaptoethanol-resistant antibody was also detected. In studies with rabbit antiserum, the complement fixation test was found to be as sensitive as the hemagglutination test for detection of anticapsular antibody. It is not clear why detectable levels of complement-fixing antibody do not develop more often in patients with pneumococcal pneumonia. Studies of purified anticapsular antibody would be of interest to determine whether or not these antibodies are restricted to immunoglobulin subclasses having a limited capacity to fix complement."}
{"id": "PMID:22490", "title": "Fluoride uptake by Streptococcus mutans 6715.", "content": "The short-term kinetics of fluoride uptake by cells from 20- to 22-h cultures of Streptococcus mutans strain 6715 were studied using rapid filtration and centrifugation techniques. Saline-suspended organisms were diluted with fluoride-containing solutions buffered at four different pH values (2.0, 4.0, 5.5, and 8.2). Fluoride disappearance from the medium was inversely related to pH and to the duration of the exposure at any given pH. The uptake was rapid and extensive at the lower pH values and decreased as the pH increased. Media fluoride concentrations subsequently increased; i.e., fluoride was released from the cells. The presence of glucose, cyanide, or iodoacetate did not influence the results. However, preincubation of the cells in fluoride-free buffers, followed by the addition of fluoride, reduced fluoride uptake markedly. Cell-to-media pH gradients were determined by the distribution of 14C-labeled 5,5-dimethyl-2,4-oxazolidinedione. Fluoride uptake was found to be a function of the magnitude of the pH gradient (P less than 0.001). It is hypothesized that fluoride uptake occurs by the diffusion of hydrogen fluoride and the subsequent trapping of ionic fluoride.", "contents": "Fluoride uptake by Streptococcus mutans 6715. The short-term kinetics of fluoride uptake by cells from 20- to 22-h cultures of Streptococcus mutans strain 6715 were studied using rapid filtration and centrifugation techniques. Saline-suspended organisms were diluted with fluoride-containing solutions buffered at four different pH values (2.0, 4.0, 5.5, and 8.2). Fluoride disappearance from the medium was inversely related to pH and to the duration of the exposure at any given pH. The uptake was rapid and extensive at the lower pH values and decreased as the pH increased. Media fluoride concentrations subsequently increased; i.e., fluoride was released from the cells. The presence of glucose, cyanide, or iodoacetate did not influence the results. However, preincubation of the cells in fluoride-free buffers, followed by the addition of fluoride, reduced fluoride uptake markedly. Cell-to-media pH gradients were determined by the distribution of 14C-labeled 5,5-dimethyl-2,4-oxazolidinedione. Fluoride uptake was found to be a function of the magnitude of the pH gradient (P less than 0.001). It is hypothesized that fluoride uptake occurs by the diffusion of hydrogen fluoride and the subsequent trapping of ionic fluoride."}
{"id": "PMID:22491", "title": "Binding of lectins to Streptococcus mutans cells and type-specific polysaccharides, and effect on adherence.", "content": "The lectin concanavalin A (Con A) agglutinated the cells of 13 of 15 strains of the seven serotypes of Streptococcus mutans in an 18-h incubation period. Strains of types a, d, f, and g agglutinated within 2 h. Strains of a, d, and f were also agglutinated in 2 h by the castor bean lectin RCA. S. sanguis, S. salivarius, S. bovis, Actinomyces viscosus, A. naeslundii, and Lactobacillus plantarum were agglutinated within 2 h. The S. mutans type f polysaccharide was precipitated by Con A. The a, b, c, d, and e polysaccharides were not precipitated. Glucan from d and e strains of S. mutans and dextran T2000 were also precipitated by Con A. D-glucose inhibited the agglutination of type f cells by Con A and the agglutination of type d cells by D-galactose. The quantity of [acetyl-3H]Con A bound was not proportional to the degree of agglutination. Cells grown in sucrose medium bound more Con A than those grown in glucose medium. After treatment with dextranase, the sucrose-grown cells bound two- to fourfold more Con A. The binding of Con A to the type-specific polysaccharide or to teichoic acid could not be determined by the use of specific antibody due to the binding of Con A to the antibody globulin on the cell surface. Con A bound to S. mutans cells did not inhibit the activity of cell-bound glucosyltransferase, glucan synthesis, and in vitro adherence. Bound Con A also did not inhibit the ability of heat-treated cells to bind glucosyltransferase, synthesize glucan, and produce in vitro adherence.", "contents": "Binding of lectins to Streptococcus mutans cells and type-specific polysaccharides, and effect on adherence. The lectin concanavalin A (Con A) agglutinated the cells of 13 of 15 strains of the seven serotypes of Streptococcus mutans in an 18-h incubation period. Strains of types a, d, f, and g agglutinated within 2 h. Strains of a, d, and f were also agglutinated in 2 h by the castor bean lectin RCA. S. sanguis, S. salivarius, S. bovis, Actinomyces viscosus, A. naeslundii, and Lactobacillus plantarum were agglutinated within 2 h. The S. mutans type f polysaccharide was precipitated by Con A. The a, b, c, d, and e polysaccharides were not precipitated. Glucan from d and e strains of S. mutans and dextran T2000 were also precipitated by Con A. D-glucose inhibited the agglutination of type f cells by Con A and the agglutination of type d cells by D-galactose. The quantity of [acetyl-3H]Con A bound was not proportional to the degree of agglutination. Cells grown in sucrose medium bound more Con A than those grown in glucose medium. After treatment with dextranase, the sucrose-grown cells bound two- to fourfold more Con A. The binding of Con A to the type-specific polysaccharide or to teichoic acid could not be determined by the use of specific antibody due to the binding of Con A to the antibody globulin on the cell surface. Con A bound to S. mutans cells did not inhibit the activity of cell-bound glucosyltransferase, glucan synthesis, and in vitro adherence. Bound Con A also did not inhibit the ability of heat-treated cells to bind glucosyltransferase, synthesize glucan, and produce in vitro adherence."}
{"id": "PMID:22492", "title": "Cell envelope of Neisseria gonorrhoeae: penicillin enhancement of peptidoglycan hydrolysis.", "content": "The addition of 10 microgram of penicillin G per ml to log-phase cultures of Neisseria gonorrhoeae JW-31 (minimum inhibitory concentration for penicillin G, less than 0.007 microgram/ml) resulted in cellular lysis after a lag of 30 min. Penicillin markedly decreased the rate of peptidoglycan synthesis and enhanced the rate of hydrolysis of existing peptidoglycan. Hydrolysis was initiated immediately after addition of penicillin; cellular lysis did not occur until a considerable percentage of the peptidoglycan had been degraded. Cellular lysis was not due to penicillin per se but resulted from inhibition of cell wall synthesis. When cells were grown in media buffered with N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid at pH 6, penicillin did not cause lysis; however, at this pH, peptidoglycan hydrolysis occurred and cells lost viability at the same rate as in the control (pH 7.2). We suggest that the stability of gonococci grown at pH 6 is related to increased stability of the outer membrane. The penicillin-enhanced rate of peptidoglycan hydrolysis decreased approximately 50% at pH 6.0. Penicillin-enhanced lysis, peptidoglycan hydrolysis, and loss of viability were also markedly reduced in cells grown at 28 degrees C.", "contents": "Cell envelope of Neisseria gonorrhoeae: penicillin enhancement of peptidoglycan hydrolysis. The addition of 10 microgram of penicillin G per ml to log-phase cultures of Neisseria gonorrhoeae JW-31 (minimum inhibitory concentration for penicillin G, less than 0.007 microgram/ml) resulted in cellular lysis after a lag of 30 min. Penicillin markedly decreased the rate of peptidoglycan synthesis and enhanced the rate of hydrolysis of existing peptidoglycan. Hydrolysis was initiated immediately after addition of penicillin; cellular lysis did not occur until a considerable percentage of the peptidoglycan had been degraded. Cellular lysis was not due to penicillin per se but resulted from inhibition of cell wall synthesis. When cells were grown in media buffered with N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid at pH 6, penicillin did not cause lysis; however, at this pH, peptidoglycan hydrolysis occurred and cells lost viability at the same rate as in the control (pH 7.2). We suggest that the stability of gonococci grown at pH 6 is related to increased stability of the outer membrane. The penicillin-enhanced rate of peptidoglycan hydrolysis decreased approximately 50% at pH 6.0. Penicillin-enhanced lysis, peptidoglycan hydrolysis, and loss of viability were also markedly reduced in cells grown at 28 degrees C."}
{"id": "PMID:22493", "title": "Adhesion of Escherichia coli to human uroepithelial cells in vitro.", "content": "Optimal conditions for in vitro adherence of Escherichia coli to uroepithelial cells, previously shown to more efficient for strains causing acute symptomatic than that for strains causing \"asymptomatic\" urinary tract infections, were investigated. Uroepithelial cells from fresh morning urine of healthy individuals and E. coli bacteria from patients with various forms of urinary tract infeciton were used. Adhesion was found to vary, between individuals and epithelial cell types, with epithelial cell viability, bacterial cultivation medium and growth phase, number of bacteria added to the epithelial cells, and incubation time and temperature. Adhesion was also influenced by variations in pH and osmolarity. Optimal test conditions were obtained with post-log-phase bacterial cultures grown on nutrient broth when 10(8) bacteria were added to 10(5) epithelial cells and incubated for 60 min. Considerable variation was found between experiments done on different days, whereas the variation between duplicates was small. The method described may provide a useful tool in the study of the host-parasite relationship in urinary tract infections.", "contents": "Adhesion of Escherichia coli to human uroepithelial cells in vitro. Optimal conditions for in vitro adherence of Escherichia coli to uroepithelial cells, previously shown to more efficient for strains causing acute symptomatic than that for strains causing \"asymptomatic\" urinary tract infections, were investigated. Uroepithelial cells from fresh morning urine of healthy individuals and E. coli bacteria from patients with various forms of urinary tract infeciton were used. Adhesion was found to vary, between individuals and epithelial cell types, with epithelial cell viability, bacterial cultivation medium and growth phase, number of bacteria added to the epithelial cells, and incubation time and temperature. Adhesion was also influenced by variations in pH and osmolarity. Optimal test conditions were obtained with post-log-phase bacterial cultures grown on nutrient broth when 10(8) bacteria were added to 10(5) epithelial cells and incubated for 60 min. Considerable variation was found between experiments done on different days, whereas the variation between duplicates was small. The method described may provide a useful tool in the study of the host-parasite relationship in urinary tract infections."}
{"id": "PMID:22495", "title": "Serum-derived immunosuppressive substances. II. An evaluation of various sources for an endogenous regulator of lymphocyte activation.", "content": "Four published methods (ion-exchange chromatography, heat, molecular sieving and alcohol fractionation) for the preparation of fractions of normal sera and tissues which possess immunosuppressive activity are compared. Human and bovine serum and human, bovine and ovine tissues including spleen, placenta and thymus were investigated as sources of substances which were immunosuppressive when added to mixed lymphocyte cultures and when injected into mice 24 h before antigenic challenge. Cohn fraction IV of human serum purified by ion-exchange chromatography at pH 5 was the most convenient preparation examined. The problems of establishing the nature of or the identity between substances being studied in different laboratories are discussed and the recommendation is made that a standard assay for activity be adopted.", "contents": "Serum-derived immunosuppressive substances. II. An evaluation of various sources for an endogenous regulator of lymphocyte activation. Four published methods (ion-exchange chromatography, heat, molecular sieving and alcohol fractionation) for the preparation of fractions of normal sera and tissues which possess immunosuppressive activity are compared. Human and bovine serum and human, bovine and ovine tissues including spleen, placenta and thymus were investigated as sources of substances which were immunosuppressive when added to mixed lymphocyte cultures and when injected into mice 24 h before antigenic challenge. Cohn fraction IV of human serum purified by ion-exchange chromatography at pH 5 was the most convenient preparation examined. The problems of establishing the nature of or the identity between substances being studied in different laboratories are discussed and the recommendation is made that a standard assay for activity be adopted."}
{"id": "PMID:22496", "title": "On the nature of the presumed receptor for IgE on mast cells. IV. Inhibition of the PCA-blocking activity of cell-free particulate preparations and intact rat peritoneal mast cells by inhibitors of proteases.", "content": "The incubation of IgE-containing solutions from rat serum with particulate preparations from rat peritoneal mast cells results in the disappearance of some of the PCA-reactive IgE in the solution. This PCA blocking assay was used to measure the 'binding' of IgE to intact rat mast cells or to particulate preparations derived from mast cells. The PCA-blocking activity at pH 4.8 was up to 100-fold greater than that seen at a physiologic pH of 6.6. PCA-blodking activity was inhibited at both these pH conditions by high concentrations of several trypsin inhibitors. The inhibitors were generally more active at the more acid pH. Among the active inhibitors were soybean and limabean trypsin inhibitors, chymostatin, and p-nitrophenyl-p'-guanidinobenzoate. Inhibitors of acid proteases, such as pepstatin and diazaacetylnorleucine methyl ester were inactive. The results support the proposition that under certain conditions IgE degradation by a specific proteolytic enzyme which is located uniquely on the plasma membrane of mast cells can account for a major portion of the PCA-blocking activity of these cells.", "contents": "On the nature of the presumed receptor for IgE on mast cells. IV. Inhibition of the PCA-blocking activity of cell-free particulate preparations and intact rat peritoneal mast cells by inhibitors of proteases. The incubation of IgE-containing solutions from rat serum with particulate preparations from rat peritoneal mast cells results in the disappearance of some of the PCA-reactive IgE in the solution. This PCA blocking assay was used to measure the 'binding' of IgE to intact rat mast cells or to particulate preparations derived from mast cells. The PCA-blocking activity at pH 4.8 was up to 100-fold greater than that seen at a physiologic pH of 6.6. PCA-blodking activity was inhibited at both these pH conditions by high concentrations of several trypsin inhibitors. The inhibitors were generally more active at the more acid pH. Among the active inhibitors were soybean and limabean trypsin inhibitors, chymostatin, and p-nitrophenyl-p'-guanidinobenzoate. Inhibitors of acid proteases, such as pepstatin and diazaacetylnorleucine methyl ester were inactive. The results support the proposition that under certain conditions IgE degradation by a specific proteolytic enzyme which is located uniquely on the plasma membrane of mast cells can account for a major portion of the PCA-blocking activity of these cells."}
{"id": "PMID:22497", "title": "The insulin-like action of Bordetella pertussis vaccine in rats.", "content": "Treatment of rats with Bordetella pertussis vaccine significantly lowered the blood sugar level 4 days later but the vaccine did not alter the level in diabetic rats. The vaccine, like insulin, raised glycogen levels in liver, skeletal muscle and heart and reduced the plasma free fatty acid concentration. The action of a beta-adrenoceptor blocker was potentiated by the vaccine but not by insulin. Part of the hypoglycaemic action of the vaccine is probably due to beta-adrenoceptor blockade.", "contents": "The insulin-like action of Bordetella pertussis vaccine in rats. Treatment of rats with Bordetella pertussis vaccine significantly lowered the blood sugar level 4 days later but the vaccine did not alter the level in diabetic rats. The vaccine, like insulin, raised glycogen levels in liver, skeletal muscle and heart and reduced the plasma free fatty acid concentration. The action of a beta-adrenoceptor blocker was potentiated by the vaccine but not by insulin. Part of the hypoglycaemic action of the vaccine is probably due to beta-adrenoceptor blockade."}
{"id": "PMID:22498", "title": "Chemotactic activity of guinea pig eosinophils for the ECF-A acidic tetrapeptides, histamine, histamine metabolites, and the effect of H1- and H2-receptor antagonists.", "content": "Histamine and one of its major metabolites, imidazoleacetic acid, were selectively chemotactic for guinea pig eosinophils, whereas L-histidine, 1,4-methylimidazoleacetic acid, 1,4-methylhistamine and N-acetylhistamine were inactive. The response to histamine was unaffected by concentrations of eosinophils of between 30 and greater than 90% but it was abrogated by preincubation of the cells with histamine prior to assay (self-deactivation). Eosinophilotaxis was also inhibited by H1-(mepyramine-) and H2-)burimamide)-receptor antagonists at high doses (10(-3)m), although at lower concentrations (10(-5) M) inhibition was principally associated with burimamide. The human tetrapeptide, alanine-glycine-serine-glutamic acid, and the analogue, valine-glycine-aspartic acid-glutamic acid, were inactive whereas alanine-glycine-serine-glutamic acid was chemotactic for the guinea pig eosinophil. These results support the concept that the tissue accumulation of eosinophils following anaphylaxis depends on a complex interaction of factors, which in part may be mediated by H2 receptors on the target cells. There may be species differences in the composition of ECF-A.", "contents": "Chemotactic activity of guinea pig eosinophils for the ECF-A acidic tetrapeptides, histamine, histamine metabolites, and the effect of H1- and H2-receptor antagonists. Histamine and one of its major metabolites, imidazoleacetic acid, were selectively chemotactic for guinea pig eosinophils, whereas L-histidine, 1,4-methylimidazoleacetic acid, 1,4-methylhistamine and N-acetylhistamine were inactive. The response to histamine was unaffected by concentrations of eosinophils of between 30 and greater than 90% but it was abrogated by preincubation of the cells with histamine prior to assay (self-deactivation). Eosinophilotaxis was also inhibited by H1-(mepyramine-) and H2-)burimamide)-receptor antagonists at high doses (10(-3)m), although at lower concentrations (10(-5) M) inhibition was principally associated with burimamide. The human tetrapeptide, alanine-glycine-serine-glutamic acid, and the analogue, valine-glycine-aspartic acid-glutamic acid, were inactive whereas alanine-glycine-serine-glutamic acid was chemotactic for the guinea pig eosinophil. These results support the concept that the tissue accumulation of eosinophils following anaphylaxis depends on a complex interaction of factors, which in part may be mediated by H2 receptors on the target cells. There may be species differences in the composition of ECF-A."}
{"id": "PMID:22499", "title": "Experimental models for prevention of graft-versus-host reaction in bone marrow transfusion. II. Inability to prevent graft-versus-host reaction in an H-2 identical combination.", "content": "Splenomegaly was strong in the degree and continued for a long period of time in adult F1 hybrids between AKR (H-2k) and C3H/He (H-2k) mice after transfer of spleen cells from normal C3H/He mice. In spleen cells of such F1 recipients, cytotoxicity was detected by an in vivo neutralization test using methylcholanthrene-induced sarcoma or AKR origin as target cells. All of newborn F1 recipients died within 17 days after cell transfer. Induction of splenomegaly and cytotoxicity was not prevented by repeated pretreatments of donors with sonicated AKR spleen cells in saline, which suppressed completely such phenomena of graft-versus-host reaction in an H-2 nonidentical combination. Induction of cytotoxicity in the spleen of F1 recipients was not prevented by a pretreatment of donors with AKR spleen cells in complete Freund's adjuvant, which suppressed the induction of cytotoxicity in an H-2 nonidentical combination. Graft-versus-host reaction appears to be stronger in a combination between parental strains of which major histocompatibility antigens were identical.", "contents": "Experimental models for prevention of graft-versus-host reaction in bone marrow transfusion. II. Inability to prevent graft-versus-host reaction in an H-2 identical combination. Splenomegaly was strong in the degree and continued for a long period of time in adult F1 hybrids between AKR (H-2k) and C3H/He (H-2k) mice after transfer of spleen cells from normal C3H/He mice. In spleen cells of such F1 recipients, cytotoxicity was detected by an in vivo neutralization test using methylcholanthrene-induced sarcoma or AKR origin as target cells. All of newborn F1 recipients died within 17 days after cell transfer. Induction of splenomegaly and cytotoxicity was not prevented by repeated pretreatments of donors with sonicated AKR spleen cells in saline, which suppressed completely such phenomena of graft-versus-host reaction in an H-2 nonidentical combination. Induction of cytotoxicity in the spleen of F1 recipients was not prevented by a pretreatment of donors with AKR spleen cells in complete Freund's adjuvant, which suppressed the induction of cytotoxicity in an H-2 nonidentical combination. Graft-versus-host reaction appears to be stronger in a combination between parental strains of which major histocompatibility antigens were identical."}
{"id": "PMID:22500", "title": "Experimental models for prevention of graft-versus-host reaction in bone marrow transfution. III. Reversible and irreversible differentiation of lymphocytes destined for cytotoxicity to effector cells for splenomegaly.", "content": "When lymphoid cells were obtained from AKR donors 12 h after a treatment with C57BL/L cells in complete Freund's adjuvant and transferred to (AKR X C57BL/6) F1 mice, splenomegaly in F1 recipients was augmented but cytotoxicity was suppressed. The suppression of cytotoxicity was antigen-specific. When cell transfer was carried out at stages as early as 3 or 6 h after the treatment of donors, cytotoxicity was enhanced but splenomegaly was suppressed. Irreversible deviation of immune response from the generation of cytotoxicity to the development of splenomegaly appears to occur within 12 h after such a treatment of donors.", "contents": "Experimental models for prevention of graft-versus-host reaction in bone marrow transfution. III. Reversible and irreversible differentiation of lymphocytes destined for cytotoxicity to effector cells for splenomegaly. When lymphoid cells were obtained from AKR donors 12 h after a treatment with C57BL/L cells in complete Freund's adjuvant and transferred to (AKR X C57BL/6) F1 mice, splenomegaly in F1 recipients was augmented but cytotoxicity was suppressed. The suppression of cytotoxicity was antigen-specific. When cell transfer was carried out at stages as early as 3 or 6 h after the treatment of donors, cytotoxicity was enhanced but splenomegaly was suppressed. Irreversible deviation of immune response from the generation of cytotoxicity to the development of splenomegaly appears to occur within 12 h after such a treatment of donors."}
{"id": "PMID:22501", "title": "Psychotropic drugs: mechanism of action at the neurotransmitter level.", "content": "Although the intimate mechanism by which psychotropic agents exert their therapeutic effects is still not completely clear, a large bulk of evidence supports the existence of a close correlation between their clinical antipsychotic acitivity and the ability to affect by different mechanisms brain monoamines and/or other real or putative neurotransmitters. Neuroleptic drugs of the phenothiazine type and related classes possess a blocking effect on dopaminergic transmission in nigro-striatal, mesolimbic and mesocortical areas; experiments supporting both a pre-and post-synaptic site of action have been described, together with the interference at the molecular level with DA-sensitive adenylate cyclase activity. In addition, anticholinergic activity and increase in GABA turnover in the striatum have been given as evidence to explain for some neuroleptics (e.g sulpiride, clozapine) lack of extrapyramidal side-effects. Anxiolytics seem to produce their therapeutic effect through a decrease in catecholaminegic and serotoninergic turnover although new avenues have been opened by some recent reports indicating a facilitation of GABAergic and glycinergic transmission in CNS.", "contents": "Psychotropic drugs: mechanism of action at the neurotransmitter level. Although the intimate mechanism by which psychotropic agents exert their therapeutic effects is still not completely clear, a large bulk of evidence supports the existence of a close correlation between their clinical antipsychotic acitivity and the ability to affect by different mechanisms brain monoamines and/or other real or putative neurotransmitters. Neuroleptic drugs of the phenothiazine type and related classes possess a blocking effect on dopaminergic transmission in nigro-striatal, mesolimbic and mesocortical areas; experiments supporting both a pre-and post-synaptic site of action have been described, together with the interference at the molecular level with DA-sensitive adenylate cyclase activity. In addition, anticholinergic activity and increase in GABA turnover in the striatum have been given as evidence to explain for some neuroleptics (e.g sulpiride, clozapine) lack of extrapyramidal side-effects. Anxiolytics seem to produce their therapeutic effect through a decrease in catecholaminegic and serotoninergic turnover although new avenues have been opened by some recent reports indicating a facilitation of GABAergic and glycinergic transmission in CNS."}
{"id": "PMID:22502", "title": "Reactivity of sulfhydryl group in peptides and poly-peptides with p-nitrophenylacetate. S to N acyl shift in cysteine.", "content": "The activity of poly (Cys-Ser-Phe-Glu-Glu) and related polypeptides as models of cysteine-proteases towards p-nitrophenylacetate was studied. The reaction leads to the formation of an S-acetylated form which proved to be quite stable, except at very high pH values. The presence of imidazole groups in the neighbourhood of sulfhydryl functions seems to result in an enhancement of the activity, which we attributed to a cooperative interaction. However, this interaction has no effect upon the S-deacylation rate. In the case of cysteine we found that the reaction with NPA occurred through a S to N acyl shift. Our results lead us to suggest that, unless convincing proofs of deacylation are given,  the various models of cysteine-proteases studied so far do not behave as \"true catalysts\".", "contents": "Reactivity of sulfhydryl group in peptides and poly-peptides with p-nitrophenylacetate. S to N acyl shift in cysteine. The activity of poly (Cys-Ser-Phe-Glu-Glu) and related polypeptides as models of cysteine-proteases towards p-nitrophenylacetate was studied. The reaction leads to the formation of an S-acetylated form which proved to be quite stable, except at very high pH values. The presence of imidazole groups in the neighbourhood of sulfhydryl functions seems to result in an enhancement of the activity, which we attributed to a cooperative interaction. However, this interaction has no effect upon the S-deacylation rate. In the case of cysteine we found that the reaction with NPA occurred through a S to N acyl shift. Our results lead us to suggest that, unless convincing proofs of deacylation are given,  the various models of cysteine-proteases studied so far do not behave as \"true catalysts\"."}
{"id": "PMID:22503", "title": "Critical residues in D-amino acid oxidase. A pulse-radiolysis and inactivation study.", "content": "The enzyme D-amino acid oxidase and its apoenzyme have been irradiated at pH 5.5--10 under conditions designed to assess the inactivating effect of OH radicals and the selective free radicals Br2- and (SCN)2-. Near neutral pH, removal of the coenzyme FAD from the enzyme results in greater inactivation by selective free-radical attack. From pulse-radiolysis spectra, this increase is associated with attack on tyrosine and tryptophan residues in the protein. A large increase in inactivation of both the haloenzyme and apoenzyme by selective free-radical attack is seen with increasing alkalinity. This is consistent with attack on tyrosine being of major importance.", "contents": "Critical residues in D-amino acid oxidase. A pulse-radiolysis and inactivation study. The enzyme D-amino acid oxidase and its apoenzyme have been irradiated at pH 5.5--10 under conditions designed to assess the inactivating effect of OH radicals and the selective free radicals Br2- and (SCN)2-. Near neutral pH, removal of the coenzyme FAD from the enzyme results in greater inactivation by selective free-radical attack. From pulse-radiolysis spectra, this increase is associated with attack on tyrosine and tryptophan residues in the protein. A large increase in inactivation of both the haloenzyme and apoenzyme by selective free-radical attack is seen with increasing alkalinity. This is consistent with attack on tyrosine being of major importance."}
{"id": "PMID:22504", "title": "Alkaline endonuclease(s) activity in the thymus and spleen of normal and irradiated mice.", "content": "Evidence has been found on an alkaline endonuclease activity in the cytoplasmic and nuclear fraction isolated from the thymus and spleen mice. The chromatin-associated endonuclease activity was identified only in the spleen. The enzyme(s) was active on both single- and double-stranded DNA, but the reaction was faster if single-stranded DNA was used as a substrate. Maximum activity was found in the pH range of 7.9 to 8.1 in the presence of 10 mM Mg2+ and 1 mM Ca2+. The enzyme(s) splits DNA, yielding 3'-hydroxyl terminated polynucleotides. It is suggested that this alkaline endonuclease(s) is responsible for the formation of deoxyribopolynucleotides in the thymus and spleen of irradiated mice.", "contents": "Alkaline endonuclease(s) activity in the thymus and spleen of normal and irradiated mice. Evidence has been found on an alkaline endonuclease activity in the cytoplasmic and nuclear fraction isolated from the thymus and spleen mice. The chromatin-associated endonuclease activity was identified only in the spleen. The enzyme(s) was active on both single- and double-stranded DNA, but the reaction was faster if single-stranded DNA was used as a substrate. Maximum activity was found in the pH range of 7.9 to 8.1 in the presence of 10 mM Mg2+ and 1 mM Ca2+. The enzyme(s) splits DNA, yielding 3'-hydroxyl terminated polynucleotides. It is suggested that this alkaline endonuclease(s) is responsible for the formation of deoxyribopolynucleotides in the thymus and spleen of irradiated mice."}
{"id": "PMID:22505", "title": "Radiostrontium distribution measured in vitro between bound and free forms in the soft tissues of rat.", "content": "The distribution of 89Sr (carrier-free) in the bound (non-diffusible) and free (diffusible) forms was studied in vitro in the soft tissues of the albino rat by the ultrafiltration method. The influence of factors such as time and temperature of incubation with 89Sr, concentration and medium of the homogenate, pH and age of the animal on the binding of 89Sr was investigated. The binding increased with rise in pH, being maximum in the pH range 7.0--9.0. The distribution pattern varied with the tissues, the bound form (at pH 7.4) being as high as 84 per cent in the small intestine and as low as 20 per cent in the skin, whereas it was about 40--45 per cent in kidney, liver, lung, skeletal muscle and blood serum. The bound form in most of the tissues of the weanling rats was in general lower than that in 6-month or 1-year-old rats. In the serum, 89Sr was mostly bound to globulins. The bound form of 89Sr was also determined by the method of equilibrium dialysis for comparison.", "contents": "Radiostrontium distribution measured in vitro between bound and free forms in the soft tissues of rat. The distribution of 89Sr (carrier-free) in the bound (non-diffusible) and free (diffusible) forms was studied in vitro in the soft tissues of the albino rat by the ultrafiltration method. The influence of factors such as time and temperature of incubation with 89Sr, concentration and medium of the homogenate, pH and age of the animal on the binding of 89Sr was investigated. The binding increased with rise in pH, being maximum in the pH range 7.0--9.0. The distribution pattern varied with the tissues, the bound form (at pH 7.4) being as high as 84 per cent in the small intestine and as low as 20 per cent in the skin, whereas it was about 40--45 per cent in kidney, liver, lung, skeletal muscle and blood serum. The bound form in most of the tissues of the weanling rats was in general lower than that in 6-month or 1-year-old rats. In the serum, 89Sr was mostly bound to globulins. The bound form of 89Sr was also determined by the method of equilibrium dialysis for comparison."}
{"id": "PMID:22507", "title": "Antioxidant function of vitamin A.", "content": "Feeding of 100 000 I.U. of Vitamin A on alternate days, five times to rats, resulted in a marked lowering in in vitro lipid peroxidation of the tissue hemogenates. alpha-Tocopherol or DPPD supplementation along with A still further reduced the in vitro lipid peroxidation of the tissues. Vitamin A in large doses increased the antioxygenic potential of the tissues, and it is suggested that retinol also might be considered as a potential antioxidant similar to tocopherol in animal nutrition.", "contents": "Antioxidant function of vitamin A. Feeding of 100 000 I.U. of Vitamin A on alternate days, five times to rats, resulted in a marked lowering in in vitro lipid peroxidation of the tissue hemogenates. alpha-Tocopherol or DPPD supplementation along with A still further reduced the in vitro lipid peroxidation of the tissues. Vitamin A in large doses increased the antioxygenic potential of the tissues, and it is suggested that retinol also might be considered as a potential antioxidant similar to tocopherol in animal nutrition."}
{"id": "PMID:22514", "title": "Hemorrhagic fever with renal syndrome: report of 11 observations.", "content": "Based on the observation of 11 patients (10 males and 1 female), the occurrence of hemorrhagic fever with renal syndrome in two new geographic areas of Romania is reported. Two patients died within several hours after admission. The other nine recovered gradually. In four patients hemodialysis was necessary. A complete recovery of renal functions one year after onset could be proved in four patients. The clinical, laboratory, morphopathological (necroptic and bioptic), epidemiologic and evolutive characteristics of the disease, especially the main features supporting the diagnosis of hemorrhagic fever with renal syndrome, are discussed.", "contents": "Hemorrhagic fever with renal syndrome: report of 11 observations. Based on the observation of 11 patients (10 males and 1 female), the occurrence of hemorrhagic fever with renal syndrome in two new geographic areas of Romania is reported. Two patients died within several hours after admission. The other nine recovered gradually. In four patients hemodialysis was necessary. A complete recovery of renal functions one year after onset could be proved in four patients. The clinical, laboratory, morphopathological (necroptic and bioptic), epidemiologic and evolutive characteristics of the disease, especially the main features supporting the diagnosis of hemorrhagic fever with renal syndrome, are discussed."}
{"id": "PMID:22515", "title": "[Comparison of the effects of pipothiazine palmitate and fluphenazine decanoate. Results of a multicenter double-blind trial].", "content": "Fluphenazine decanoate and pipothiazine palmitate were compared concerning their effect and side-effects. 61 schizophrenic patients were treated up to 6 months in a multicenter double-blind trial. Assessments were made on day 0 and after 5, 10, 17 and 22 weeks of treatment using the AMP system. Pipothiazine palmitate was injected every 4th week and fluphenazine decanoate every 3rd week. The most often applied dosage was 100 mg pipothiazine palmitate and 25 or 37.5 mg fluphenazine decanoate. Data analysis of the AMP system at the symptom level showed the better antipsychotic effect of pipothiazine palmitate. A comparison between the two groups by means of analysis of covariance at the syndrome level showed no statistical significant differences between the effects of fluphenazine decanoate and pipothiazine palmitate.", "contents": "[Comparison of the effects of pipothiazine palmitate and fluphenazine decanoate. Results of a multicenter double-blind trial]. Fluphenazine decanoate and pipothiazine palmitate were compared concerning their effect and side-effects. 61 schizophrenic patients were treated up to 6 months in a multicenter double-blind trial. Assessments were made on day 0 and after 5, 10, 17 and 22 weeks of treatment using the AMP system. Pipothiazine palmitate was injected every 4th week and fluphenazine decanoate every 3rd week. The most often applied dosage was 100 mg pipothiazine palmitate and 25 or 37.5 mg fluphenazine decanoate. Data analysis of the AMP system at the symptom level showed the better antipsychotic effect of pipothiazine palmitate. A comparison between the two groups by means of analysis of covariance at the syndrome level showed no statistical significant differences between the effects of fluphenazine decanoate and pipothiazine palmitate."}
{"id": "PMID:22516", "title": "Dissolution of urinary stones by calcium-chelating agents: A study using a model system.", "content": "Pellets made by dispersing microcrystals of calcium oxalate monohydrate throughout an organic matrix have served as models for kidney stones in studies of factors governing their dissolution by calcium-chelating agents. These factors include pH, ionic strength, concentration of chelating agent, and addition of other acids and bases. The method shows good reproducibility. Results have been applied to improving a clinical procedure for kidney stone dissolution.", "contents": "Dissolution of urinary stones by calcium-chelating agents: A study using a model system. Pellets made by dispersing microcrystals of calcium oxalate monohydrate throughout an organic matrix have served as models for kidney stones in studies of factors governing their dissolution by calcium-chelating agents. These factors include pH, ionic strength, concentration of chelating agent, and addition of other acids and bases. The method shows good reproducibility. Results have been applied to improving a clinical procedure for kidney stone dissolution."}
{"id": "PMID:22517", "title": "Immunochemical characterization of Lymantri dispar NPV hemagglutinin: protein-carbohydrate interaction.", "content": "The agglutination of chicken erythrocytes by Lymantria dispar nuclear polyhedrosis virus polyhedrin has been shown to provide specific virus identification. Selected mono- and oligosaccharides, present in blood group substances, were assayed by the Land-steiner hapten inhibition technique for specific inhibition of polyhedrin hemagglutination. N-acetylgalactosamine and N-acetylglucosamine inhibit to the greatest extent; galactosamine, glucosamine and fucose to a lesser extent. The hapten inhibition data suggest that a monosaccharide possessing an equatorial 2-acetamido group interacts most avidly with the polyhedrin-combining site. Bergold demonstrated that the polyhedrin dissociates into six subunits at a pH greater than 10.0. Diafiltration equilibrium and Scatchard analysis indicate that N-acetylgalactosamine binds most avidly to the polyhedrin (Kd = 1.7 X 10(-6)) which contains six available sites, suggesting that one hemagglutination site resides on each subunit. Since virions derived in vivo and polyhedrin are serologically cross-reactive, this protein-carbohydrate interaction may play a role in host infectivity by providing a receptor site for virus attachment to target cells.", "contents": "Immunochemical characterization of Lymantri dispar NPV hemagglutinin: protein-carbohydrate interaction. The agglutination of chicken erythrocytes by Lymantria dispar nuclear polyhedrosis virus polyhedrin has been shown to provide specific virus identification. Selected mono- and oligosaccharides, present in blood group substances, were assayed by the Land-steiner hapten inhibition technique for specific inhibition of polyhedrin hemagglutination. N-acetylgalactosamine and N-acetylglucosamine inhibit to the greatest extent; galactosamine, glucosamine and fucose to a lesser extent. The hapten inhibition data suggest that a monosaccharide possessing an equatorial 2-acetamido group interacts most avidly with the polyhedrin-combining site. Bergold demonstrated that the polyhedrin dissociates into six subunits at a pH greater than 10.0. Diafiltration equilibrium and Scatchard analysis indicate that N-acetylgalactosamine binds most avidly to the polyhedrin (Kd = 1.7 X 10(-6)) which contains six available sites, suggesting that one hemagglutination site resides on each subunit. Since virions derived in vivo and polyhedrin are serologically cross-reactive, this protein-carbohydrate interaction may play a role in host infectivity by providing a receptor site for virus attachment to target cells."}
{"id": "PMID:22528", "title": "Hope for that hopeless essay test.", "content": "Despite the fact that essay tests have been under attack, teachers continue to use them. Although preparation and scoring of questions can be problematic, they can, however, be employed successfully if the teacher 1) recognizes their limitations, 2) prepares the questions carefully so that they will test what the teacher intends, and 3) uses methods of scoring that will judge the answers as accurately as possible. With continued practice, the teachers can develop skill in using the essay format.", "contents": "Hope for that hopeless essay test. Despite the fact that essay tests have been under attack, teachers continue to use them. Although preparation and scoring of questions can be problematic, they can, however, be employed successfully if the teacher 1) recognizes their limitations, 2) prepares the questions carefully so that they will test what the teacher intends, and 3) uses methods of scoring that will judge the answers as accurately as possible. With continued practice, the teachers can develop skill in using the essay format."}
{"id": "PMID:22530", "title": "Surface properties of cells of some methicillin-resistant strains of Staphylococcus aureus.", "content": "Methicillin-sensitive (MS) cells of Staphylococcus aureus had a minimum electrophoretic mobility at pH 4.5, whereas methicillin-resistant (MR) strains showed only a slight plateau effect. Trypsin removed the trough effect of the MS Oxford strain. There was no correlation between surface lipid and resistance in MR strains. Cell walls of MS strains contained much more teichoic acid than walls of MR strains. Lysostaphin lysed all MR and MS strains, and mucopeptide does not appear to be involved in resistance to methicillin.", "contents": "Surface properties of cells of some methicillin-resistant strains of Staphylococcus aureus. Methicillin-sensitive (MS) cells of Staphylococcus aureus had a minimum electrophoretic mobility at pH 4.5, whereas methicillin-resistant (MR) strains showed only a slight plateau effect. Trypsin removed the trough effect of the MS Oxford strain. There was no correlation between surface lipid and resistance in MR strains. Cell walls of MS strains contained much more teichoic acid than walls of MR strains. Lysostaphin lysed all MR and MS strains, and mucopeptide does not appear to be involved in resistance to methicillin."}
{"id": "PMID:22533", "title": "Phosphagen and lactate contents of m. quadriceps femoris of man after exercise.", "content": "Muscle biopsies were taken from the m. quadriceps femoris of man immediately after termination of dynamic and isometric exercise. These were analyzed for adenosine triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-phosphate (AMP), phosphorylcreatine (PC), creatine, pyruvate and lactate. Regardless of type, intensity, and duration of the preceding exercise, a general pattern of the relation between high-energy phosphates and lactate content could be observed. PG showed a nonlinear relationship to the muscle lactate content. The ratio of ATP to ADP appeared to decrease linearly when lactate content increased. The relationships are believed to be the consequence of a steady-state condition where muscle pH is one of the major determining factors.", "contents": "Phosphagen and lactate contents of m. quadriceps femoris of man after exercise. Muscle biopsies were taken from the m. quadriceps femoris of man immediately after termination of dynamic and isometric exercise. These were analyzed for adenosine triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-phosphate (AMP), phosphorylcreatine (PC), creatine, pyruvate and lactate. Regardless of type, intensity, and duration of the preceding exercise, a general pattern of the relation between high-energy phosphates and lactate content could be observed. PG showed a nonlinear relationship to the muscle lactate content. The ratio of ATP to ADP appeared to decrease linearly when lactate content increased. The relationships are believed to be the consequence of a steady-state condition where muscle pH is one of the major determining factors."}
{"id": "PMID:22534", "title": "Biochemical-genetic study of the first enzyme of histidine biosynthesis in Salmonella typhimurium: substrate and feedback binding regions.", "content": "Twenty-five strains of Salmonella typhimurium containing different mutations in the first gene of histidine biosynthesis were studied to correlate regions of the genetic map with biochemical functions. These strains contained either missense, double-frameshift, or suppressed nonsense mutations, all of which resulted in altered, though active, enzymes. Each mutant enzyme was assayed for activity in the presence of varying concentrations of the feedback inhibitor L-histidine or the substrates ATP and 5-phosphoribosyl-1-pyrophosphate. The feedback properties and substrate kinetics of each mutant enzyme were compared to wild-type values, and these results indicated that the following functions were correlated with regions of the hisG gene: feedback inhibition in two general areas, including regions IA and IB and regions V, VI, and VII; ATP binding in two general areas, including regions IA, IB, and II and regions V, VI, and VII; and 5-phosphoribosyl-1-pyrophosphate binding in two general areas, including regions IB, II, and III and regions V and VI.", "contents": "Biochemical-genetic study of the first enzyme of histidine biosynthesis in Salmonella typhimurium: substrate and feedback binding regions. Twenty-five strains of Salmonella typhimurium containing different mutations in the first gene of histidine biosynthesis were studied to correlate regions of the genetic map with biochemical functions. These strains contained either missense, double-frameshift, or suppressed nonsense mutations, all of which resulted in altered, though active, enzymes. Each mutant enzyme was assayed for activity in the presence of varying concentrations of the feedback inhibitor L-histidine or the substrates ATP and 5-phosphoribosyl-1-pyrophosphate. The feedback properties and substrate kinetics of each mutant enzyme were compared to wild-type values, and these results indicated that the following functions were correlated with regions of the hisG gene: feedback inhibition in two general areas, including regions IA and IB and regions V, VI, and VII; ATP binding in two general areas, including regions IA, IB, and II and regions V, VI, and VII; and 5-phosphoribosyl-1-pyrophosphate binding in two general areas, including regions IB, II, and III and regions V and VI."}
{"id": "PMID:22535", "title": "gltB gene and regulation of nitrogen metabolism by glutamine synthetase in Escherichia coli.", "content": "A mutant (gltB) of Escherichia coli lacking glutamate synthase (GOGAT) was unable to utilize a wide variety of compounds as sole nitrogen source (e.g., arginine, proline, gamma-aminobutyrate, and glycine). Among revertants of these Asm- strains selected on one of these compounds (e.g., arginine, proline, or gamma-aminobutyrate) were those that produce glutamine synthetase (GS) constitutively (GlnC phenotype). These revertants had a pleiotropically restored ability to grow on compounds that are metabolized to glutamate. This suggested that the expression of the genes responsible for the metabolism of these nitrogen sources was regulated by GS. An examination of the regulation of proline oxidase confirmed this hypothesis. The differential sensitivities of GlnC and wild-type strains to low concentrations (0.1 mM) of the glutamine analog L-methionine-DL-sulfoximine supported the conclusion that the synthesis of a glutamine permease was also positively controlled by GS. During the course of this study we found that the reported position of the locus (gltB) for glutamate synthase is incorrect. We have relocated this gene to be 44% linked to the argG locus by P1 transduction. Further mapping has shown that the locus previously called aspB is in reality the gltB locus and that the \"suppressor\" of the aspB mutation (A. M. Reiner, J. Bacteriol. 97:1431-1436, 1969) is the locus for glutamate dehydrogenase (gdhA).", "contents": "gltB gene and regulation of nitrogen metabolism by glutamine synthetase in Escherichia coli. A mutant (gltB) of Escherichia coli lacking glutamate synthase (GOGAT) was unable to utilize a wide variety of compounds as sole nitrogen source (e.g., arginine, proline, gamma-aminobutyrate, and glycine). Among revertants of these Asm- strains selected on one of these compounds (e.g., arginine, proline, or gamma-aminobutyrate) were those that produce glutamine synthetase (GS) constitutively (GlnC phenotype). These revertants had a pleiotropically restored ability to grow on compounds that are metabolized to glutamate. This suggested that the expression of the genes responsible for the metabolism of these nitrogen sources was regulated by GS. An examination of the regulation of proline oxidase confirmed this hypothesis. The differential sensitivities of GlnC and wild-type strains to low concentrations (0.1 mM) of the glutamine analog L-methionine-DL-sulfoximine supported the conclusion that the synthesis of a glutamine permease was also positively controlled by GS. During the course of this study we found that the reported position of the locus (gltB) for glutamate synthase is incorrect. We have relocated this gene to be 44% linked to the argG locus by P1 transduction. Further mapping has shown that the locus previously called aspB is in reality the gltB locus and that the \"suppressor\" of the aspB mutation (A. M. Reiner, J. Bacteriol. 97:1431-1436, 1969) is the locus for glutamate dehydrogenase (gdhA)."}
{"id": "PMID:22536", "title": "Purification and properties of an extracellular protease from Myxococcus virescens.", "content": "An extracellular protease from Myxococcus virescens was purified by phosphate precipitation, gel exclusion, and ion-exchange chromatography. The enzyme appeared homogeneous upon disc electrophoresis. The molecular weight of the protease was estimated to be 26,000. The enzyme was rapidly inactivated by ethylenediaminetetraacetate, but the activity could be partially restored by divalent cations. Diisopropylphosphorofluoridate inhibited enzyme activity completely. Michaelis-Menten kinetics were obeyed with casein and hemoglobin as substrates. First-order kinetics were obtained with elastin as the substrate, provided trypsin was in excess. Petidolytic activity indicated that the peptide bonds hydrolyzed by the enzyme were mainly those involving amino acids with nonpolar side chains.", "contents": "Purification and properties of an extracellular protease from Myxococcus virescens. An extracellular protease from Myxococcus virescens was purified by phosphate precipitation, gel exclusion, and ion-exchange chromatography. The enzyme appeared homogeneous upon disc electrophoresis. The molecular weight of the protease was estimated to be 26,000. The enzyme was rapidly inactivated by ethylenediaminetetraacetate, but the activity could be partially restored by divalent cations. Diisopropylphosphorofluoridate inhibited enzyme activity completely. Michaelis-Menten kinetics were obeyed with casein and hemoglobin as substrates. First-order kinetics were obtained with elastin as the substrate, provided trypsin was in excess. Petidolytic activity indicated that the peptide bonds hydrolyzed by the enzyme were mainly those involving amino acids with nonpolar side chains."}
{"id": "PMID:22537", "title": "Ammonia assimilation and glutamate formation in Caulobacter crescentus.", "content": "In the dimorphic bacterium Caulobacter crescentus, ammonia assimilation occurs only via the combined action of the enzymes glutamine synthetase and glutamate synthase. Mutants auxotrophic for glutamate lacked glutamate synthase activity, and the mutations leading to the glutamate auxotrophy appeared to lie at two distinct genetic loci. Both glutamate synthase and glutamine synthetase activities were subject to regulation by repression. Glutamate synthase activity was highest in cultures grown in minimal medium with ammonia as sole nitrogen source and was about fivefold lower in rich broth. Glutamine synthetase activity was highest in cells grown with growth-rate-limiting amounts of ammonia as nitrogen source and was about fourfold lower in rich broth. In addition, glutamine synthetase activity appeared to be regulated by an adenylylation system like that described for Escherichia coli.", "contents": "Ammonia assimilation and glutamate formation in Caulobacter crescentus. In the dimorphic bacterium Caulobacter crescentus, ammonia assimilation occurs only via the combined action of the enzymes glutamine synthetase and glutamate synthase. Mutants auxotrophic for glutamate lacked glutamate synthase activity, and the mutations leading to the glutamate auxotrophy appeared to lie at two distinct genetic loci. Both glutamate synthase and glutamine synthetase activities were subject to regulation by repression. Glutamate synthase activity was highest in cultures grown in minimal medium with ammonia as sole nitrogen source and was about fivefold lower in rich broth. Glutamine synthetase activity was highest in cells grown with growth-rate-limiting amounts of ammonia as nitrogen source and was about fourfold lower in rich broth. In addition, glutamine synthetase activity appeared to be regulated by an adenylylation system like that described for Escherichia coli."}
{"id": "PMID:22538", "title": "Purification and properties of nitroalkane oxidase from Fusarium oxysporum.", "content": "A nitroalkane-oxidizing enzyme, which was inducibly formed by addition of nitroethane to the medium was purified to homogeneity from an extract of Fusarium oxysporum (IFO 5942) with an overall yield of about 20%. The enzyme catalyzed the oxidative denitrification of 1-nitropropane as follows: CH2(NO2)CH2CH3 + O2 + H2O leads to OHCCH2CH3 + HNO2 + H2O2. In addition to 1-nitropropane, 3-nitro-2-pentanol, 2-nitropropane, and nitrocyclohexane are good substrates; the enzyme is designated \"nitroalkane oxidase\" (EC class 1.7.3). The enzyme has a molecular weight of approximately 185,000 and consists of four subunits identical in molecular weight (47,000). Flavin adenine dinucleotide was required for the enzyme activity and could be replaced in part by riboflavin 5'-phosphate. The maximum reactivity was found at about pH 8.0. The enzyme was inhibited significantly by HgCl2, KCN, p-chloromercuribenzoate, and N-ethylmaleimide. The Michaelis constants are as follows: 1-nitropropane, 1.54 mM; 2-nitropropane, 7.40 mM; nitroethane, 1.00 mM; 3-nitro-2-pentanol, 3.08 mM; nitrocyclohexane, 0.90 mM; and flavin adenine dinucleotide, 1.33 micrometer.", "contents": "Purification and properties of nitroalkane oxidase from Fusarium oxysporum. A nitroalkane-oxidizing enzyme, which was inducibly formed by addition of nitroethane to the medium was purified to homogeneity from an extract of Fusarium oxysporum (IFO 5942) with an overall yield of about 20%. The enzyme catalyzed the oxidative denitrification of 1-nitropropane as follows: CH2(NO2)CH2CH3 + O2 + H2O leads to OHCCH2CH3 + HNO2 + H2O2. In addition to 1-nitropropane, 3-nitro-2-pentanol, 2-nitropropane, and nitrocyclohexane are good substrates; the enzyme is designated \"nitroalkane oxidase\" (EC class 1.7.3). The enzyme has a molecular weight of approximately 185,000 and consists of four subunits identical in molecular weight (47,000). Flavin adenine dinucleotide was required for the enzyme activity and could be replaced in part by riboflavin 5'-phosphate. The maximum reactivity was found at about pH 8.0. The enzyme was inhibited significantly by HgCl2, KCN, p-chloromercuribenzoate, and N-ethylmaleimide. The Michaelis constants are as follows: 1-nitropropane, 1.54 mM; 2-nitropropane, 7.40 mM; nitroethane, 1.00 mM; 3-nitro-2-pentanol, 3.08 mM; nitrocyclohexane, 0.90 mM; and flavin adenine dinucleotide, 1.33 micrometer."}
{"id": "PMID:22539", "title": "Association-dissociation of the flavoprotein hog kidney D-amino acid oxidase. Determination of the monomer-dimer equilibrium constant and the energetics of subunit association.", "content": "The enzyme concentration dependence of spectrophotometric titrations of hog kidney D-amino acid oxidase [EC 1.4.3.3] with p-aminobenzoate was studied. The monomer-dimer equilibrium constant of the oxidized holoenzyme at 25 degrees C was estimated to be 7 X 10(5)M-1 at pH 7.5 and 4X 10(6)M-1 at pH 8.3. The energetics of subunit association are discussed.", "contents": "Association-dissociation of the flavoprotein hog kidney D-amino acid oxidase. Determination of the monomer-dimer equilibrium constant and the energetics of subunit association. The enzyme concentration dependence of spectrophotometric titrations of hog kidney D-amino acid oxidase [EC 1.4.3.3] with p-aminobenzoate was studied. The monomer-dimer equilibrium constant of the oxidized holoenzyme at 25 degrees C was estimated to be 7 X 10(5)M-1 at pH 7.5 and 4X 10(6)M-1 at pH 8.3. The energetics of subunit association are discussed."}
{"id": "PMID:22540", "title": "Light-induced pH changes and changes in absorbance of pH indicators in Rhodospirillum rubrum chromatophores.", "content": "1. The light-induced pH change of chromatophore suspensions from Rhodospirillum rubrum was stimulated significantly and similarly by KCl, NaCl, LiCl, RbCl, CsCl, MgCl2, MnCl2, and CaCl2. In the dark, the pH of chromatophore suspensions decreased immediately and markedly on adding these salts. 2. The light-induced pH change stimulated by KCl plus valinomycin was inhibited by LiCl and NaCl, but not by RbCl. 3. The optimum pH values for light-induced pH change and photosynthetic ATP formation were around 5 and 8, respectively. The amount of chromatophore-bound ubiquinone-10 reduced in the light was independent of pH from 5 to 9. At pH 8, the number of protons incorporated into chromatophores in the light was one-half of the number of ubiquinone-10 molecules reduced in the light. 4. Among several pH indicators tested, bromothymol blue (BTB) and neutral red (NR) showed absorbance changes on illumination of chromatophores. Although the pH change indicated by the absorbance change was opposite to the light-induced pH change of the medium, the effect of KCl on the absorbance changes of BTB and NR, and the effect of valinomycin on that of NR, but not on that of BTB, were similar to those on the light-induced pH change. 5. The light-induced absorbance change of BTB was significantly inhibited by NR, whereas that of NR was hardly influenced by BTB. 6. Oligomycin stimulated the light-induced absorbance change of BTB under either non-phosphorylating or phosphorylating conditions. On the other hand, that of NR under phosphorylating conditions was 50% of that under non-phosphorylating conditions, and was increased by oligomycin.", "contents": "Light-induced pH changes and changes in absorbance of pH indicators in Rhodospirillum rubrum chromatophores. 1. The light-induced pH change of chromatophore suspensions from Rhodospirillum rubrum was stimulated significantly and similarly by KCl, NaCl, LiCl, RbCl, CsCl, MgCl2, MnCl2, and CaCl2. In the dark, the pH of chromatophore suspensions decreased immediately and markedly on adding these salts. 2. The light-induced pH change stimulated by KCl plus valinomycin was inhibited by LiCl and NaCl, but not by RbCl. 3. The optimum pH values for light-induced pH change and photosynthetic ATP formation were around 5 and 8, respectively. The amount of chromatophore-bound ubiquinone-10 reduced in the light was independent of pH from 5 to 9. At pH 8, the number of protons incorporated into chromatophores in the light was one-half of the number of ubiquinone-10 molecules reduced in the light. 4. Among several pH indicators tested, bromothymol blue (BTB) and neutral red (NR) showed absorbance changes on illumination of chromatophores. Although the pH change indicated by the absorbance change was opposite to the light-induced pH change of the medium, the effect of KCl on the absorbance changes of BTB and NR, and the effect of valinomycin on that of NR, but not on that of BTB, were similar to those on the light-induced pH change. 5. The light-induced absorbance change of BTB was significantly inhibited by NR, whereas that of NR was hardly influenced by BTB. 6. Oligomycin stimulated the light-induced absorbance change of BTB under either non-phosphorylating or phosphorylating conditions. On the other hand, that of NR under phosphorylating conditions was 50% of that under non-phosphorylating conditions, and was increased by oligomycin."}
{"id": "PMID:22543", "title": "Calf liver nuclear N-acetyltransferases. Purification and properties of two enzymes with both spermidine acetyltransferase and histone acetyltransferase activities.", "content": "Calf liver contains two nuclear N-acetyltransferases which are separated by chromatography on hydroxylapatite. Both acetyltransferase A and acetyltransferase B will transfer acetate from acetyl-CoA to either histone or spermidine. The same protein catalyzes the reaction with both substrates; this is shown by a constant ratio of spermidine to histone activity over a 5,000-fold purification and identical heat denaturation kinetics for both spermidine and histone acetyltransferase activity with each enzyme. Histone is preferentially acetylated when both acceptors are present. Both enzymes preferentially acetylate polyamines (spermidine, spermine, and diaminodipropylamine) to diamines. Acetyltransferase A acetylates histones in the order: whole histone greater than H4 greater than H2A greater than H3 greater than H2B greater than H1; acetyltransferase B in the order: whole histone greater than H4 = H3 greater than H2A greater than H2B greater than H1. Michaelis constants are 2 X 10(-4)M for spermidine and 9 X 10(-6)M for acetyl-CoA. Acetyltransferase A has a molecular weight of 150,000; acetyltransferase B 175,000. Both enzymes are strongly inhibited by p-chloromercuribenzoate and weakly inhibited by EDTA.", "contents": "Calf liver nuclear N-acetyltransferases. Purification and properties of two enzymes with both spermidine acetyltransferase and histone acetyltransferase activities. Calf liver contains two nuclear N-acetyltransferases which are separated by chromatography on hydroxylapatite. Both acetyltransferase A and acetyltransferase B will transfer acetate from acetyl-CoA to either histone or spermidine. The same protein catalyzes the reaction with both substrates; this is shown by a constant ratio of spermidine to histone activity over a 5,000-fold purification and identical heat denaturation kinetics for both spermidine and histone acetyltransferase activity with each enzyme. Histone is preferentially acetylated when both acceptors are present. Both enzymes preferentially acetylate polyamines (spermidine, spermine, and diaminodipropylamine) to diamines. Acetyltransferase A acetylates histones in the order: whole histone greater than H4 greater than H2A greater than H3 greater than H2B greater than H1; acetyltransferase B in the order: whole histone greater than H4 = H3 greater than H2A greater than H2B greater than H1. Michaelis constants are 2 X 10(-4)M for spermidine and 9 X 10(-6)M for acetyl-CoA. Acetyltransferase A has a molecular weight of 150,000; acetyltransferase B 175,000. Both enzymes are strongly inhibited by p-chloromercuribenzoate and weakly inhibited by EDTA."}
{"id": "PMID:22545", "title": "Tyrosine hydroxylase. Activation by protein phosphorylation and end product inhibition.", "content": "Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent Km value for 6-methyltetrahydropterin. Removal of endogenous catecholamines by gel filtration or cation exchange results in a similar activation. Phosphorylation causes only a small additional reduction in the apparent Km for reduced pterin in striatal extracts from which catecholamines have been removed. Kinetic analysis indicates that protein phosphorylation causes a significant increase in the Ki for end product dopamine, whereas gel filtration or cation exchange treatment has little effect on the dopamine Ki value. None of the above treatments appears to change the molecular weight of the enzyme. At physiological concentrations of dopamine, the increase in Ki by phosphorylation would effectively release tyrosine hydroxylase from end product feedback inhibition.", "contents": "Tyrosine hydroxylase. Activation by protein phosphorylation and end product inhibition. Protein phosphorylation activates tyrosine hydroxylase in crude extracts of rat striatum, hypothalamus, and adrenal glands by a reduction in the apparent Km value for 6-methyltetrahydropterin. Removal of endogenous catecholamines by gel filtration or cation exchange results in a similar activation. Phosphorylation causes only a small additional reduction in the apparent Km for reduced pterin in striatal extracts from which catecholamines have been removed. Kinetic analysis indicates that protein phosphorylation causes a significant increase in the Ki for end product dopamine, whereas gel filtration or cation exchange treatment has little effect on the dopamine Ki value. None of the above treatments appears to change the molecular weight of the enzyme. At physiological concentrations of dopamine, the increase in Ki by phosphorylation would effectively release tyrosine hydroxylase from end product feedback inhibition."}
{"id": "PMID:22546", "title": "Oxalate and spin-labeled oxalate as probes of the anion binding site of human transferrin. Metal to anion distance.", "content": "The spin-labeled anion N-[4-(2,2,6,6-tetramethylpiperidin-1-oxyl)] oxamate has been synthesized and characterized. In the presence of this compound, a specific iron-transferrin-anion complex is formed, as evidenced by the development of a characteristic red color. No EPR signal was observed for the nitroxyl radical in the protein complex, presumably due to broadening of the signal by the paramagnetic metal ion. Failure to observe a signal implies that the metal to nitroxyl distance is less than or equal to 6 A. This suggests that the anion is directly attached to the metal ion in the protein. The pH dependence of iron dissociation from iron-transferrin-oxalate is also reported. This complex is more stable at low pH than iron-transferrin-carbonate.", "contents": "Oxalate and spin-labeled oxalate as probes of the anion binding site of human transferrin. Metal to anion distance. The spin-labeled anion N-[4-(2,2,6,6-tetramethylpiperidin-1-oxyl)] oxamate has been synthesized and characterized. In the presence of this compound, a specific iron-transferrin-anion complex is formed, as evidenced by the development of a characteristic red color. No EPR signal was observed for the nitroxyl radical in the protein complex, presumably due to broadening of the signal by the paramagnetic metal ion. Failure to observe a signal implies that the metal to nitroxyl distance is less than or equal to 6 A. This suggests that the anion is directly attached to the metal ion in the protein. The pH dependence of iron dissociation from iron-transferrin-oxalate is also reported. This complex is more stable at low pH than iron-transferrin-carbonate."}
{"id": "PMID:22547", "title": "Quaternary states of methemoglobin and its valence-hybrid. A pulse radiolysis study.", "content": "Using the pulse radiolysis technique on solutions of stripped adult human methemoglobin, we found that the heme-iron within a single subunit in the tetramer was reduced to iron(II). The valence-hybrid thus formed was reacted with oxygen and with carbon monoxide. Kinetics of the reactions were studied. The effects of pH, inositol hexaphosphate, and temperature on these reactions were examined. The kinetics of the ligation of O2 and CO were used to characterize the affinity states of the valence-hybrid and its parent methemoglobin. Our results support the description of stripped methemoglobin A as residing in an R state. In the presence of inositol hexaphosphate methemoglobin is stabilized in a T state, but it switches into a high affinity state when the pH is raised a0ove 8.0. This structural transition was not found to coincide with the switch of spin state of the heme-iron that accompanies the ionization of water in aquomethemoglobin A.", "contents": "Quaternary states of methemoglobin and its valence-hybrid. A pulse radiolysis study. Using the pulse radiolysis technique on solutions of stripped adult human methemoglobin, we found that the heme-iron within a single subunit in the tetramer was reduced to iron(II). The valence-hybrid thus formed was reacted with oxygen and with carbon monoxide. Kinetics of the reactions were studied. The effects of pH, inositol hexaphosphate, and temperature on these reactions were examined. The kinetics of the ligation of O2 and CO were used to characterize the affinity states of the valence-hybrid and its parent methemoglobin. Our results support the description of stripped methemoglobin A as residing in an R state. In the presence of inositol hexaphosphate methemoglobin is stabilized in a T state, but it switches into a high affinity state when the pH is raised a0ove 8.0. This structural transition was not found to coincide with the switch of spin state of the heme-iron that accompanies the ionization of water in aquomethemoglobin A."}
{"id": "PMID:22549", "title": "Increase in hepatic tyrosine aminotransferase mRNA during enzyme induction by N6,O2'-dibutyryl cyclic AMP.", "content": "Tyrosine aminotransferase mRNA was quantitated by translation in a cell-free system derived from wheat germ followed by specific immunoprecipitation of the newly synthesized enzyme subunit. Hepatic poly(A)-containg RNA prepared from rats treated for 4 h with N6, O2'-dibutyryl cyclic AMP and theophylline was approximately 5.6 times more active in directing the synthesis of the tyrosine aminotransferase subunit relative to untreated controls. The overall template activity of the RNA prepared from control and cyclic AMP-treated animals was virtually identical, demonstrating that the cyclic nucleotide effect was specific for the tyrosine aminotransferase mRNA. At all times, after a single injection of dibutyryl cyclic AMP and theophylline, the increase in hepatic enzyme activity was accompanied by corresponding induction in the level of functional tyrosine aminotransferase mRNA. Other inducers of tyrosine aminotransferase, such as glucagon and hydrocortisone, also increased the level of tyrosine aminotransferase mRNA in proportion to their effect on enzyme activity. The RNA polymerase II inhibitor, alpha-amanitin, completely blocked the dibutyryl cyclic AMP-mediated increase in tyrosine aminotransferase mRNA activity. These studies demonstrate that, in intact animals, the induction of tyrosine aminotransferase activity by dibutyryl cyclic AMP can be completely accounted for by a corresponding increase in the level of functional mRNA coding for the enzyme.", "contents": "Increase in hepatic tyrosine aminotransferase mRNA during enzyme induction by N6,O2'-dibutyryl cyclic AMP. Tyrosine aminotransferase mRNA was quantitated by translation in a cell-free system derived from wheat germ followed by specific immunoprecipitation of the newly synthesized enzyme subunit. Hepatic poly(A)-containg RNA prepared from rats treated for 4 h with N6, O2'-dibutyryl cyclic AMP and theophylline was approximately 5.6 times more active in directing the synthesis of the tyrosine aminotransferase subunit relative to untreated controls. The overall template activity of the RNA prepared from control and cyclic AMP-treated animals was virtually identical, demonstrating that the cyclic nucleotide effect was specific for the tyrosine aminotransferase mRNA. At all times, after a single injection of dibutyryl cyclic AMP and theophylline, the increase in hepatic enzyme activity was accompanied by corresponding induction in the level of functional tyrosine aminotransferase mRNA. Other inducers of tyrosine aminotransferase, such as glucagon and hydrocortisone, also increased the level of tyrosine aminotransferase mRNA in proportion to their effect on enzyme activity. The RNA polymerase II inhibitor, alpha-amanitin, completely blocked the dibutyryl cyclic AMP-mediated increase in tyrosine aminotransferase mRNA activity. These studies demonstrate that, in intact animals, the induction of tyrosine aminotransferase activity by dibutyryl cyclic AMP can be completely accounted for by a corresponding increase in the level of functional mRNA coding for the enzyme."}
{"id": "PMID:22550", "title": "Molecular weights of aggregation states of Busycon hemocyanin.", "content": "Molecular weights of all hemocyanin aggregates which can be homogeneously isolated have been measured by sedimentation equilibrium. The larger aggregates, which are the ones present under physiological conditions, are, to a very close approximation, integral multiples of a 4.4 x 10(6)-dalton, 60 S species. Dissociation of the 60 S species at high pH gives heterogeneous samples in which the smallest species has a molecular weight of 300,000. The smallest subunit which can be produced in denaturing solvents also has a molecular weight of 300,000.", "contents": "Molecular weights of aggregation states of Busycon hemocyanin. Molecular weights of all hemocyanin aggregates which can be homogeneously isolated have been measured by sedimentation equilibrium. The larger aggregates, which are the ones present under physiological conditions, are, to a very close approximation, integral multiples of a 4.4 x 10(6)-dalton, 60 S species. Dissociation of the 60 S species at high pH gives heterogeneous samples in which the smallest species has a molecular weight of 300,000. The smallest subunit which can be produced in denaturing solvents also has a molecular weight of 300,000."}
{"id": "PMID:22551", "title": "The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast.", "content": "The rapid catabolism of glutamine by the cultured human lymphoblast line WI-L2 can be inhibited greater than 95% by incubation of cell suspensions with 6-diazo-5-oxo-L-norleucine (DON). The inhibition persists for at least four hours after removal of DON from the cell suspension. The exposure of cells to DON ihibits over 95% of the glutaminase activity measured in lysates in the presence of either phosphate or maleate. Similarly, gamma-glutamyl transpeptidase, assayed with gamma-glutamyl-p-nitroanilide as substrate and glycyglycine as acceptor, is inhibited over 90%. DON-treated and control cells accumulated radioactive material from suspensions containing [14C]-L-glutamine at similar initial rates; the radioactive material accumulated by the DON-treated cells is all recoverable as glutamine while the radioactive material accumulated by untreated cells is principally recovered as glutamate.", "contents": "The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast. The rapid catabolism of glutamine by the cultured human lymphoblast line WI-L2 can be inhibited greater than 95% by incubation of cell suspensions with 6-diazo-5-oxo-L-norleucine (DON). The inhibition persists for at least four hours after removal of DON from the cell suspension. The exposure of cells to DON ihibits over 95% of the glutaminase activity measured in lysates in the presence of either phosphate or maleate. Similarly, gamma-glutamyl transpeptidase, assayed with gamma-glutamyl-p-nitroanilide as substrate and glycyglycine as acceptor, is inhibited over 90%. DON-treated and control cells accumulated radioactive material from suspensions containing [14C]-L-glutamine at similar initial rates; the radioactive material accumulated by the DON-treated cells is all recoverable as glutamine while the radioactive material accumulated by untreated cells is principally recovered as glutamate."}
{"id": "PMID:22552", "title": "Role of the vacuolar apparatus in augmented protein degradation in cultured fibroblasts.", "content": "Rat embryo fibroblasts, grown in Eagle's MEM with 10% serum, showed a rapid increase in autophagic vacuoles when placed in MEM with 0-1% serum. Concurrent with this response, degradation of cellular proteins showed a 2-fold increase. We did not find any increases in cathepsin D, beta-glucuronidase, beta-galactosidase, and beta-glucosidase, or proteolytic activity of cell homogenates at pH 3.7 towards endogenous substrates. Homogenates prepared in 250 mM sucrose at pH 7.0 showed a 40% increase in protein breakdown. These data support the hypothesis that the induced increase in proteolysis, characteristic of cells placed in a nutritionally deficient medium, is effected by an activated vacuolar apparatus (lysosomes and autophagic vacuoles). We suggest, however, that this mechanism is distinct from normal protein turnover in the cell, but can be rapidly induced by appropriate alterations in the cellular environment. Finally, this induced proteolytic mechanism is not dependent upon an increase in lysosomal enzymes, but rather a structural alteration within the cell which effects a transfer of cellular proteins into the vacuolar apparatus.", "contents": "Role of the vacuolar apparatus in augmented protein degradation in cultured fibroblasts. Rat embryo fibroblasts, grown in Eagle's MEM with 10% serum, showed a rapid increase in autophagic vacuoles when placed in MEM with 0-1% serum. Concurrent with this response, degradation of cellular proteins showed a 2-fold increase. We did not find any increases in cathepsin D, beta-glucuronidase, beta-galactosidase, and beta-glucosidase, or proteolytic activity of cell homogenates at pH 3.7 towards endogenous substrates. Homogenates prepared in 250 mM sucrose at pH 7.0 showed a 40% increase in protein breakdown. These data support the hypothesis that the induced increase in proteolysis, characteristic of cells placed in a nutritionally deficient medium, is effected by an activated vacuolar apparatus (lysosomes and autophagic vacuoles). We suggest, however, that this mechanism is distinct from normal protein turnover in the cell, but can be rapidly induced by appropriate alterations in the cellular environment. Finally, this induced proteolytic mechanism is not dependent upon an increase in lysosomal enzymes, but rather a structural alteration within the cell which effects a transfer of cellular proteins into the vacuolar apparatus."}
{"id": "PMID:22553", "title": "Lectin-mediated agglutination of amphibian embryonic cells.", "content": "Dissociated blastula cells of Xenopus laevis are agglutinated with wheat germ agglutinin (WGA), Ricinus communis agglutinin (RCA), concanavalin A (Con A) and, to a lesser extent with soya bean agglutinin (SBA). They are not agglutinated with fucose-binding protein. Neuraminidase treatment of cells enhances their agglutinability with RCA and SBA, but has no effect on Con A- and WGA-mediated agglutinability. Treatment of cells with procaine, or xylocaine, has no effect on the cells' agglutinability or on the extrusion of lobopodia. Treatment with colchicine or cytochalasin B either separately or simultaneously has no effect on lectin-mediated agglutinability. Cells treated with cytochalasin B or colchicine and cytochalasin B simultaneously lack lobopodial extensions, while colchicine alone has no effect on these structures. Phenothiazine tranquillizers inhibit agglutination mediated by all of the above mentioned lectins. Lobopodial extensions are absent in cells treated with these compounds. Glutaraldehyde fixation inhibits RCA and WGA mediated agglutinability and reduces the Con A-mediated agglutinability. Results suggest that in this system microtubules and microfilaments are not involved in lectin-mediated agglutination.", "contents": "Lectin-mediated agglutination of amphibian embryonic cells. Dissociated blastula cells of Xenopus laevis are agglutinated with wheat germ agglutinin (WGA), Ricinus communis agglutinin (RCA), concanavalin A (Con A) and, to a lesser extent with soya bean agglutinin (SBA). They are not agglutinated with fucose-binding protein. Neuraminidase treatment of cells enhances their agglutinability with RCA and SBA, but has no effect on Con A- and WGA-mediated agglutinability. Treatment of cells with procaine, or xylocaine, has no effect on the cells' agglutinability or on the extrusion of lobopodia. Treatment with colchicine or cytochalasin B either separately or simultaneously has no effect on lectin-mediated agglutinability. Cells treated with cytochalasin B or colchicine and cytochalasin B simultaneously lack lobopodial extensions, while colchicine alone has no effect on these structures. Phenothiazine tranquillizers inhibit agglutination mediated by all of the above mentioned lectins. Lobopodial extensions are absent in cells treated with these compounds. Glutaraldehyde fixation inhibits RCA and WGA mediated agglutinability and reduces the Con A-mediated agglutinability. Results suggest that in this system microtubules and microfilaments are not involved in lectin-mediated agglutination."}
{"id": "PMID:22554", "title": "Studies on human alpha-lactalbumin: radioimmunoassay measurements in normal human breast and breast cancer.", "content": "A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a milk protein, has been developed in order to examine the effect of prolactin on the human breast in normal and diseased states. Samples of milk from nursing mothers and from men and women with galactorrhea were found to contain milligram concentrations of this protein. In serum, 8 of 25 normal men and 18 of 44 normal women had detectable concentrations of alpha-lactalbumin. Significantly higher levels of alpha-lactalbumin were found in 17 of 19 women during pregnancy who were not actively lactating. All nursing mothers were found to have distinctly elevated serum alpha-lactalbumin concentrations. In a group of 17 female patients with phenothiazine induced prolactin elevations (mean 29.4 ng/ml), the mean serum alpha-lactalbumin of 17.3 ng/ml was significantly higher than in normal female volunteers. Patients with gynecomastia were not noted to have elevated alpha-lactalbumin. In vitro, homogenates of normal breast and carcinoma tissue from the same individuals revealed that in 9 of 17 patients alpha-lactalbumin was present in higher concentrations in normal than in cancerous tissue. Overall, alpha-lactalbumin was found in 48.5% of homogenates and 41% of organ cultures of normal breast tissue from cancer patients. In contrast, it was present in only 19% of homogenates and 21% of cultures of carcinoma tissue, indicating that the cancer tissue may lose its ability to produce alpha-lactalbumin. Differences in biologic behavior were found in some tumors. In 2 cases homogenates of breast cancer tissue had much higher concentrations of alpha-lactalbumin than the normal tissue, and in 3 of 33 tumors studied in organ culture prolactin increased alpha-lactalbumin output.", "contents": "Studies on human alpha-lactalbumin: radioimmunoassay measurements in normal human breast and breast cancer. A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a milk protein, has been developed in order to examine the effect of prolactin on the human breast in normal and diseased states. Samples of milk from nursing mothers and from men and women with galactorrhea were found to contain milligram concentrations of this protein. In serum, 8 of 25 normal men and 18 of 44 normal women had detectable concentrations of alpha-lactalbumin. Significantly higher levels of alpha-lactalbumin were found in 17 of 19 women during pregnancy who were not actively lactating. All nursing mothers were found to have distinctly elevated serum alpha-lactalbumin concentrations. In a group of 17 female patients with phenothiazine induced prolactin elevations (mean 29.4 ng/ml), the mean serum alpha-lactalbumin of 17.3 ng/ml was significantly higher than in normal female volunteers. Patients with gynecomastia were not noted to have elevated alpha-lactalbumin. In vitro, homogenates of normal breast and carcinoma tissue from the same individuals revealed that in 9 of 17 patients alpha-lactalbumin was present in higher concentrations in normal than in cancerous tissue. Overall, alpha-lactalbumin was found in 48.5% of homogenates and 41% of organ cultures of normal breast tissue from cancer patients. In contrast, it was present in only 19% of homogenates and 21% of cultures of carcinoma tissue, indicating that the cancer tissue may lose its ability to produce alpha-lactalbumin. Differences in biologic behavior were found in some tumors. In 2 cases homogenates of breast cancer tissue had much higher concentrations of alpha-lactalbumin than the normal tissue, and in 3 of 33 tumors studied in organ culture prolactin increased alpha-lactalbumin output."}
{"id": "PMID:22555", "title": "Inhibition of folate enzymes by sulfasalazine.", "content": "Sulfasalazine (salicylazosulfapyridine), an agent widely used for the treatment of ileitis and colitis, is also a competitive inhibitor of intestinal folate transport (1, 2). The mechanism of action of sulfasalazine remains uncertain. To further explore the mechanism of sulfasalazine action, the interaction of the drug with the folate recognition site was tested with three enzymes: dihydrofolate reductase, methylenetetrahydrofolate reductase, and serine transhydroxymethylase, each catalyzing a reaction involving a different folate derivative. Each of these enzymes was inhibited by sulfasalazine in the same concentration range as that previously observed to inhibit intestinal folate transport; the kinetic data are consistent with a competitive mode of inhibition. Specificity of inhibition was demonstrated by the finding that the reduction of the pteridine ring of pteroylheptaglutamic acid by dihydrofolate reductase was subject to inhibition, whereas the hydrolysis of the gamma-glutamyl peptide side chain by chicken pancreas conjugase was not affected. These results are interpreted to indicate that sulfasalazine interferes with a folate recognition site which is common to these enzymes and to the intestinal transport system. Sulfasalazine, therefore, has certain properties of an antifolate drug.", "contents": "Inhibition of folate enzymes by sulfasalazine. Sulfasalazine (salicylazosulfapyridine), an agent widely used for the treatment of ileitis and colitis, is also a competitive inhibitor of intestinal folate transport (1, 2). The mechanism of action of sulfasalazine remains uncertain. To further explore the mechanism of sulfasalazine action, the interaction of the drug with the folate recognition site was tested with three enzymes: dihydrofolate reductase, methylenetetrahydrofolate reductase, and serine transhydroxymethylase, each catalyzing a reaction involving a different folate derivative. Each of these enzymes was inhibited by sulfasalazine in the same concentration range as that previously observed to inhibit intestinal folate transport; the kinetic data are consistent with a competitive mode of inhibition. Specificity of inhibition was demonstrated by the finding that the reduction of the pteridine ring of pteroylheptaglutamic acid by dihydrofolate reductase was subject to inhibition, whereas the hydrolysis of the gamma-glutamyl peptide side chain by chicken pancreas conjugase was not affected. These results are interpreted to indicate that sulfasalazine interferes with a folate recognition site which is common to these enzymes and to the intestinal transport system. Sulfasalazine, therefore, has certain properties of an antifolate drug."}
{"id": "PMID:22556", "title": "Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency.", "content": "Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl.", "contents": "Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. Cobalamin (Cbl; vitamin B(12)) malabsorption in pancreatic insufficiency can be partially corrected by bicarbonate and completely corrected by pancreatic proteases but the mechanisms involved are unknown. Because saliva contains enough R-type Cbl-binding protein (R protein) to bind all of the dietary and biliary Cbl, it is possible that R protein acts as an inhibitor of Cbl absorption and that pancreatic proteases are required to alter R protein and prevent such inhibition. To test this hypothesis we studied the ability of R protein and intrinsic factor (IF) to compete for Cbl binding and ability of pancreatic proteases to alter this competition. Human salivary R protein bound Cbl with affinities that were 50- and 3-fold higher than those of human IF at pH 2 and 8, respectively. Cbl bound to IF was transferred to an equal amount of R protein with t((1/2))'s of 2 and 90 min at pH 2 and 8, respectively, and within several hours respective ratios of R protein-Cbl/IF-Cbl of 50 and 2 were observed. Cbl bound to R protein was not transferred to IF at either pH 2 or 8. Incubation of R protein with pancreatic proteases at pH 8 led to a 150-fold decrease in its affinity for Cbl. Incubation of R protein-Cbl with pancreatic proteases led to complete transfer of Cbl to IF within 10 min. Gel filtration studies with R protein-[(57)Co]Cbl and (125)I-R protein showed that pancreatic proteases partially degraded R protein. Pancreatic proteases differed in their ability to effect these changes with trypsin > chymotrypsin > elastase. Pancreatic proteases did not alter IF in any of the parameters mentioned above. Pepsin failed to alter either R protein or IF. THESE STUDIES SUGGEST THE FOLLOWING: (a) that Cbl is bound almost exclusively to R protein in the acid milieu of the stomach, rather than to IF as has been assumed previously; (b) that Cbl remains bound to R protein in the slightly alkaline environment of the intestine until pancreatic proteases partially degrade R protein and enable Cbl to become bound exclusively to IF; and (c) that the primary defect in Cbl absorption in pancreatic insufficiency is a lack of pancreatic proteases and a failure to alter R protein and effect the transfer of Cbl to IF. These studies also suggest that the partial correction of Cbl malabsorption observed with bicarbonate is due to neutralization of gastric HCl, since at slightly alkaline, pH IF can partially compete with R protein for the initial binding and retention of Cbl."}
{"id": "PMID:22569", "title": "Comparison of the ribonucleoproteins of different rabies virus serotypes by radioimmunoassay.", "content": "Radioimmunoassay (RIA) provides a sensitive serological procedure for detecting rabies virus ribonucleoprotein (RNP) as well as its specific antibodies, RIA was carried out using highly purified RNPs labelled by the chloramine-T method. This paper describes optimal conditions for iodination of RNP with high specific activity. The optimal concentrations of 125I, RNP, chloramine-T, and reducing agent as well as the effect of pH on the reaction were investigated. RIA proved to be extremely sensitive for detection of homologous antibodies. In competition experiments the part-relationship of the group-specific RNPs of the three rabies virus serotypes (HEP, MOK and LBV) was confirmed.", "contents": "Comparison of the ribonucleoproteins of different rabies virus serotypes by radioimmunoassay. Radioimmunoassay (RIA) provides a sensitive serological procedure for detecting rabies virus ribonucleoprotein (RNP) as well as its specific antibodies, RIA was carried out using highly purified RNPs labelled by the chloramine-T method. This paper describes optimal conditions for iodination of RNP with high specific activity. The optimal concentrations of 125I, RNP, chloramine-T, and reducing agent as well as the effect of pH on the reaction were investigated. RIA proved to be extremely sensitive for detection of homologous antibodies. In competition experiments the part-relationship of the group-specific RNPs of the three rabies virus serotypes (HEP, MOK and LBV) was confirmed."}
{"id": "PMID:22573", "title": "A simple method to determine gammaglutamyl-cyclotransferase activity in erythrocytes.", "content": "A new method for the determination of erythrocyte gammaGCT is described. The method follows the release of alanine from gammaglutamyl alanine by a series of linked reactions that result in the oxidation of NADH to NAD. The pH optimum for human erythrocyte gammaGCT was found to be 9.0, and the Km for gammaglutamyl alanine was found to be 2.3 X 10(-3) M. Human erythrocytes had the highest activity of all the species studied (human, rabbit, dog, sheep, cattle, chicken).", "contents": "A simple method to determine gammaglutamyl-cyclotransferase activity in erythrocytes. A new method for the determination of erythrocyte gammaGCT is described. The method follows the release of alanine from gammaglutamyl alanine by a series of linked reactions that result in the oxidation of NADH to NAD. The pH optimum for human erythrocyte gammaGCT was found to be 9.0, and the Km for gammaglutamyl alanine was found to be 2.3 X 10(-3) M. Human erythrocytes had the highest activity of all the species studied (human, rabbit, dog, sheep, cattle, chicken)."}
{"id": "PMID:22574", "title": "Hyperlipidemia in renal failure: studies of plasma lipoproteins, hepatic triglyceride production, and tissue lipoprotein lipase in a chronically uremic rat moedl.", "content": "To determine whether hypertriglyceridemia in chronic renal failure resulted from altered production and/or removal, Sprague-Dawley rats in which chronic uremia had been induced by five-sixths nephrectomy were studied. In this model, basal plasma TG levels were higher than in controls (uremic 141 +/- 52 mg/100 ml; control 83 +/- 25; mean +/- SD; p less than 0.001) at 1 month after nephrectomy and remained significantly elevated throughout the 10-week duration of study. In the uremic animals hepatic TGSR's (Triton) were not increased (uremic 0.56 +/- 0.11 mg/min; control 0.63 +/- 0.13) and AcCoAc, the rate-limiting enzyme in hepatic lipogenesis, was significantly reduced (control 24.5 +/- 3.8 nM/min/mg protein; uremic 18.2 +/- 1.1; p less than 0.005). The TG removal system--heparin-elutable LPL activities--was similar in control and uremic animals in heart, diaphragm, and adipose tissue. However, serum from both acute and chronically uremic rats lowered adipose LPL activity (P less than 0.01). These observations suggest that in uremia (1) TG production is not increased and (2) the clearance of TG-rich lipoprotein from the circulation is reduced because of a functional impairment in LPL.", "contents": "Hyperlipidemia in renal failure: studies of plasma lipoproteins, hepatic triglyceride production, and tissue lipoprotein lipase in a chronically uremic rat moedl. To determine whether hypertriglyceridemia in chronic renal failure resulted from altered production and/or removal, Sprague-Dawley rats in which chronic uremia had been induced by five-sixths nephrectomy were studied. In this model, basal plasma TG levels were higher than in controls (uremic 141 +/- 52 mg/100 ml; control 83 +/- 25; mean +/- SD; p less than 0.001) at 1 month after nephrectomy and remained significantly elevated throughout the 10-week duration of study. In the uremic animals hepatic TGSR's (Triton) were not increased (uremic 0.56 +/- 0.11 mg/min; control 0.63 +/- 0.13) and AcCoAc, the rate-limiting enzyme in hepatic lipogenesis, was significantly reduced (control 24.5 +/- 3.8 nM/min/mg protein; uremic 18.2 +/- 1.1; p less than 0.005). The TG removal system--heparin-elutable LPL activities--was similar in control and uremic animals in heart, diaphragm, and adipose tissue. However, serum from both acute and chronically uremic rats lowered adipose LPL activity (P less than 0.01). These observations suggest that in uremia (1) TG production is not increased and (2) the clearance of TG-rich lipoprotein from the circulation is reduced because of a functional impairment in LPL."}
{"id": "PMID:22576", "title": "Cholesterol ester hydrolysis by homogenates of whole testis, seminiferous tubules and interstitial cells of mature rats.", "content": "The characteristics and localization of a cholesterol ester hydrolase enzyme in homogenates of whole testis and in isolated seminiferous tubules and interstitial cells of mature rats have been investigated. Hydrolysis of cholesteryl [1(-14)C]oleate occurred at an optimum pH of 7.0, was linearly related to time up to 5--6 h of incubation and increased linearly up to 0.25 mg protein/incubation. Hydrolytic activity was inhibited by increasing the incubation temperature from 29 to 41 degrees C and by sonication. Cholesterol ester hydrolase activity/mg protein was three times greater in homogenates of seminiferous tubules than in interstitial cells. Cholesterol ester hydrolase may function to provide precursors for use in seminiferous tubular steroid hormone biosynthesis or germ cell maturation.", "contents": "Cholesterol ester hydrolysis by homogenates of whole testis, seminiferous tubules and interstitial cells of mature rats. The characteristics and localization of a cholesterol ester hydrolase enzyme in homogenates of whole testis and in isolated seminiferous tubules and interstitial cells of mature rats have been investigated. Hydrolysis of cholesteryl [1(-14)C]oleate occurred at an optimum pH of 7.0, was linearly related to time up to 5--6 h of incubation and increased linearly up to 0.25 mg protein/incubation. Hydrolytic activity was inhibited by increasing the incubation temperature from 29 to 41 degrees C and by sonication. Cholesterol ester hydrolase activity/mg protein was three times greater in homogenates of seminiferous tubules than in interstitial cells. Cholesterol ester hydrolase may function to provide precursors for use in seminiferous tubular steroid hormone biosynthesis or germ cell maturation."}
{"id": "PMID:22579", "title": "Energetics of biological nitrogen fixation: determination of the ratio of formation of H2 to NH4+ catalysed by nitrogenase of Klebsiella pneumoniae in vivo.", "content": "Nitrogen fixation (Nif)-derepressed mutants of Klebsiella pneumoniae consumed, under optimum conditions, 7.5 to 8.5 mol glucose per mol N2 fixed. The nitrogenase system of these mutants catalysed the production of about 1.3 mol H2 per mol N2 reduced. Almost one-third of the energy as ATP and reductant used by nitrogenase in vivo may be lost in H2 production, since an ATP/2e ratio of approximately 4 was obtained. Nitrogenase-catalysed H2 production was not substantially suppressed by increasing the partial pressure of N2 from 0.2 atm (20 kPa) to 1 atm (101 kPa). In the absence of N2, H2 production catalysed by nitrogenase increased about threefold. It is concluded that nitrogenase-catalysed H2 production is of major importance in the overall efficiency of biological N2 fixation in vivo.", "contents": "Energetics of biological nitrogen fixation: determination of the ratio of formation of H2 to NH4+ catalysed by nitrogenase of Klebsiella pneumoniae in vivo. Nitrogen fixation (Nif)-derepressed mutants of Klebsiella pneumoniae consumed, under optimum conditions, 7.5 to 8.5 mol glucose per mol N2 fixed. The nitrogenase system of these mutants catalysed the production of about 1.3 mol H2 per mol N2 reduced. Almost one-third of the energy as ATP and reductant used by nitrogenase in vivo may be lost in H2 production, since an ATP/2e ratio of approximately 4 was obtained. Nitrogenase-catalysed H2 production was not substantially suppressed by increasing the partial pressure of N2 from 0.2 atm (20 kPa) to 1 atm (101 kPa). In the absence of N2, H2 production catalysed by nitrogenase increased about threefold. It is concluded that nitrogenase-catalysed H2 production is of major importance in the overall efficiency of biological N2 fixation in vivo."}
{"id": "PMID:22590", "title": "Aerobic and anaerobic bacteriology of acute otitis media in children.", "content": "Tympanocentesis and aerobic and anaerobic cultivation of the middle-ear fluid obtained was performed through one or both tympanic membranes of 62 children with acute otitis media. Aerobic bacteria alone, predominantely pneumococcus and Hemophilus influenzae, were isolated from 57% of patients; anaerobic organisms alone, most commonly Propionibacterium acnes and Peptococcus, from 15%. Thirteen percent yielded mixtures of aerobes and anaerobes, and several had multiple aerobic or anaerobic agents. The isolation of only anaerobic bacteria, supported in some patients by gram-stain observations of middle-ear fluid, suggest that these bacteria, especially Petococcus, may occasionally play a direct role in acute otitis media.", "contents": "Aerobic and anaerobic bacteriology of acute otitis media in children. Tympanocentesis and aerobic and anaerobic cultivation of the middle-ear fluid obtained was performed through one or both tympanic membranes of 62 children with acute otitis media. Aerobic bacteria alone, predominantely pneumococcus and Hemophilus influenzae, were isolated from 57% of patients; anaerobic organisms alone, most commonly Propionibacterium acnes and Peptococcus, from 15%. Thirteen percent yielded mixtures of aerobes and anaerobes, and several had multiple aerobic or anaerobic agents. The isolation of only anaerobic bacteria, supported in some patients by gram-stain observations of middle-ear fluid, suggest that these bacteria, especially Petococcus, may occasionally play a direct role in acute otitis media."}
{"id": "PMID:22591", "title": "The pharmacologic effects of furosemide therapy in the low-birth-weight infant.", "content": "The pharmacologic effects of furosemide were studied in six infants (mean gestation 30.7 weeks; mean birth weight 1,490 gm) at ages 10 to 57 days. Furosemide (for clinical indication, standardized at 1 mg/kg) was given intravenously over one minute; data were collected over the ensuing 24 hours. For three hours following furosemide administration, a significant diuresis was observed. Sodium excretion, percent fractional sodium excretion, and potassium excretion were significantly increased and urinary pH significantly decreased for six hours following the administration of furosemide. Creatinine and free water clearances were slightly elevated, although not significantly. Furosemide is an effective diuretic, the onset of pharmacologic action was within one hour, the peak action was sustained for three hours, and the duration of action was six hours. The net fluid, sodium, and potassium losses following a 1 mg/kg single dose were 28 ml, and 3.6 and 0.3 mEq/kg, respectively.", "contents": "The pharmacologic effects of furosemide therapy in the low-birth-weight infant. The pharmacologic effects of furosemide were studied in six infants (mean gestation 30.7 weeks; mean birth weight 1,490 gm) at ages 10 to 57 days. Furosemide (for clinical indication, standardized at 1 mg/kg) was given intravenously over one minute; data were collected over the ensuing 24 hours. For three hours following furosemide administration, a significant diuresis was observed. Sodium excretion, percent fractional sodium excretion, and potassium excretion were significantly increased and urinary pH significantly decreased for six hours following the administration of furosemide. Creatinine and free water clearances were slightly elevated, although not significantly. Furosemide is an effective diuretic, the onset of pharmacologic action was within one hour, the peak action was sustained for three hours, and the duration of action was six hours. The net fluid, sodium, and potassium losses following a 1 mg/kg single dose were 28 ml, and 3.6 and 0.3 mEq/kg, respectively."}
{"id": "PMID:22592", "title": "Physiologic changes induced by theophylline in the treatment of apnea in preterm infants.", "content": "Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with \"serious apnea\" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, \"specific\" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.", "contents": "Physiologic changes induced by theophylline in the treatment of apnea in preterm infants. Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with \"serious apnea\" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, \"specific\" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system."}
{"id": "PMID:22593", "title": "The microfilaria of Brugia timori (Partono et al. 1977 = Timor microfilaria, David and Edeson, 1964): morphologic description with comparison to Brugia malayi of Indonesia.", "content": "The microfilaria of Brugia timori was compared with microfilariae of Indonesian strains of periodic and subperiodic Brugia malayi using alcohol-fixed (stained) and formalin-fixed (unstained) preparations. As noted by other observers of the Timor microfilaria, the absence of a stained sheath in Giemsa preparations, a long cephalic space with a length-to-width ratio of about 3:1, and a great overall body length are features which most readily distinguish this parasite. Additionally, B. timori has greater numbers of single row nuclei in the terminal column of body cells and a lesser bulge of the cuticle surrounding nuclei in the distal portion of the tail than does B. malayi. About 60% of B. timori microfilariae were exsheathed in haemalum-stained thick blood films. Brugia timori microfilariae were found to be distinct from microfilariae of B. malayi by comparing percentages of total body length included between the cephalic tip and major internal anatomic markers.", "contents": "The microfilaria of Brugia timori (Partono et al. 1977 = Timor microfilaria, David and Edeson, 1964): morphologic description with comparison to Brugia malayi of Indonesia. The microfilaria of Brugia timori was compared with microfilariae of Indonesian strains of periodic and subperiodic Brugia malayi using alcohol-fixed (stained) and formalin-fixed (unstained) preparations. As noted by other observers of the Timor microfilaria, the absence of a stained sheath in Giemsa preparations, a long cephalic space with a length-to-width ratio of about 3:1, and a great overall body length are features which most readily distinguish this parasite. Additionally, B. timori has greater numbers of single row nuclei in the terminal column of body cells and a lesser bulge of the cuticle surrounding nuclei in the distal portion of the tail than does B. malayi. About 60% of B. timori microfilariae were exsheathed in haemalum-stained thick blood films. Brugia timori microfilariae were found to be distinct from microfilariae of B. malayi by comparing percentages of total body length included between the cephalic tip and major internal anatomic markers."}
{"id": "PMID:22594", "title": "Total surgical reconstruction for patients with abdominal muscular deficiency (\"prune-belly\") syndrome.", "content": "In the past decade, seven children with the prune-belly syndrome have been seen. Their management has consisted of immediate high tubeless urinary diversion, usually pyelostomy. Thereafter, total reconstruction has been carried out, preferably at one stage. This consists of (1) bilateral shortening, tapering and reimplantation of the ureters, (2) reduction cystoplasty, (3) bilateral orchiopexy, and (4) excision of that part of the abdominal wall that is most redundant and least endowed with musculature. This early effort at mechanical reconstruction has led to gratifying progress in six of the seven children.", "contents": "Total surgical reconstruction for patients with abdominal muscular deficiency (\"prune-belly\") syndrome. In the past decade, seven children with the prune-belly syndrome have been seen. Their management has consisted of immediate high tubeless urinary diversion, usually pyelostomy. Thereafter, total reconstruction has been carried out, preferably at one stage. This consists of (1) bilateral shortening, tapering and reimplantation of the ureters, (2) reduction cystoplasty, (3) bilateral orchiopexy, and (4) excision of that part of the abdominal wall that is most redundant and least endowed with musculature. This early effort at mechanical reconstruction has led to gratifying progress in six of the seven children."}
{"id": "PMID:22595", "title": "Technique and experience with 24-hour esophageal pH monitoring in children.", "content": "The technique and scoring system of 24-hr pH esophageal monitoring has been modified to evaluate gastroesophageal reflux in infants and children. The data from two pediatric controls and five clinical cases are presented and compared to normal adult values. This test has better objectivity, precision, sensitivity, and reliability than contrast studies, endoscopy, esophageal biopsy, acid perfusion, or acid reflux tests. The 24-hr pH monitoring assists the evaluation of sphincter maturation, pulmonary disease, and the significance of body position. With more experience, this technique could identify children at risk fo developing severe complications of reflux esophagitis and aid in the selection of candidates for surgical intervention.", "contents": "Technique and experience with 24-hour esophageal pH monitoring in children. The technique and scoring system of 24-hr pH esophageal monitoring has been modified to evaluate gastroesophageal reflux in infants and children. The data from two pediatric controls and five clinical cases are presented and compared to normal adult values. This test has better objectivity, precision, sensitivity, and reliability than contrast studies, endoscopy, esophageal biopsy, acid perfusion, or acid reflux tests. The 24-hr pH monitoring assists the evaluation of sphincter maturation, pulmonary disease, and the significance of body position. With more experience, this technique could identify children at risk fo developing severe complications of reflux esophagitis and aid in the selection of candidates for surgical intervention."}
{"id": "PMID:22596", "title": "Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine.", "content": "Physostigmine was given to 17 patients in labor, previously given scopolamine alone or meperidine and propiomazine in combination, to ascertain its effect on reversing the loss of fetal heart rate variability caused by the administration of these drugs. The results of the study indicated that scopolamine in doses of 0.65 to 1.08 milligrams diminished fetal heart rate variability in all 7 patients and physostigmine reversed this loss of fetal heart rate variability in all 7 patients within 4 to 17 minutes after injection of the first dose of physostigmine. Similar results were noted in 10 patients with the combination of meperidine, 50 mg, and propiomazine, 20 mg. It seems tenable from this study that physostigmine does cross the placental barrier and enters the fetal circulation and that this usually occurs within 3 to 17 minutes with an average of approximately 9 minutes. In the healthy fetus the loss of fetal heart rate variability caused by scopolamine, meperidine or propiomazine can be reversed by the use of physostigmine and this reversal seems abrupt and clinically measurable on the fetal monitor print out.", "contents": "Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine. Physostigmine was given to 17 patients in labor, previously given scopolamine alone or meperidine and propiomazine in combination, to ascertain its effect on reversing the loss of fetal heart rate variability caused by the administration of these drugs. The results of the study indicated that scopolamine in doses of 0.65 to 1.08 milligrams diminished fetal heart rate variability in all 7 patients and physostigmine reversed this loss of fetal heart rate variability in all 7 patients within 4 to 17 minutes after injection of the first dose of physostigmine. Similar results were noted in 10 patients with the combination of meperidine, 50 mg, and propiomazine, 20 mg. It seems tenable from this study that physostigmine does cross the placental barrier and enters the fetal circulation and that this usually occurs within 3 to 17 minutes with an average of approximately 9 minutes. In the healthy fetus the loss of fetal heart rate variability caused by scopolamine, meperidine or propiomazine can be reversed by the use of physostigmine and this reversal seems abrupt and clinically measurable on the fetal monitor print out."}
{"id": "PMID:22598", "title": "The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart.", "content": "The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed.", "contents": "The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart. The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed."}
{"id": "PMID:22600", "title": "The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats.", "content": "Treatment of normal rats with metyrapone (20 mg kg-1 day-1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids.", "contents": "The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats. Treatment of normal rats with metyrapone (20 mg kg-1 day-1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids."}
{"id": "PMID:22601", "title": "Platelets in inflammatory exudates.", "content": "In exudates of implanted sponges in the rat there are apparent accumulations of blood platelets, assessed by the light microscope, and of radioactivity from labelled platelets administered systemically. The use of more specific techniques for platelet detection showed no evidence of intact blood platelets in the exudate and the radioactivity was not associated preferentially with cellular components in the exudate.", "contents": "Platelets in inflammatory exudates. In exudates of implanted sponges in the rat there are apparent accumulations of blood platelets, assessed by the light microscope, and of radioactivity from labelled platelets administered systemically. The use of more specific techniques for platelet detection showed no evidence of intact blood platelets in the exudate and the radioactivity was not associated preferentially with cellular components in the exudate."}
{"id": "PMID:22603", "title": "Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods.", "content": "The X-ray procedure for estimation of the degree of crystallinity in digoxin is based upon measurement of the total X-ray scattering and the scattering from crystalline regions of the drug. The infrared procedures are based upon measurement of the peak height ratios, 1775/1618 and 3095/1618 cm-1. Correlation between results obtained by the two methods is good. These methods are of value in the physico-chemical characterization of digoxin, particularly as the properties may be altered by comminution.", "contents": "Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods. The X-ray procedure for estimation of the degree of crystallinity in digoxin is based upon measurement of the total X-ray scattering and the scattering from crystalline regions of the drug. The infrared procedures are based upon measurement of the peak height ratios, 1775/1618 and 3095/1618 cm-1. Correlation between results obtained by the two methods is good. These methods are of value in the physico-chemical characterization of digoxin, particularly as the properties may be altered by comminution."}
{"id": "PMID:22604", "title": "The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions.", "content": "Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions.", "contents": "The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions. Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions."}
{"id": "PMID:22616", "title": "Loss of antibacterial preservatives from contact lens solutions during storage.", "content": "The preservative content of 34 commercially available contact lens solutions has been determined. Over half of the solutions contained less than 90% of the stated preservative content. Storage tests conducted at 40 degrees, using both simulated and commercially available contact lens solutions in plastics containers of the type used to present these products showed that thiomersal and chlorbutol appeared to be sorbed by these containers in contrast to benzalkonium chloride and chlorhexidine gluconate which interacted mainly by a surface adsorption process. The extent of any interactions was dependent upon the type of plastics material used to fabricate the container.", "contents": "Loss of antibacterial preservatives from contact lens solutions during storage. The preservative content of 34 commercially available contact lens solutions has been determined. Over half of the solutions contained less than 90% of the stated preservative content. Storage tests conducted at 40 degrees, using both simulated and commercially available contact lens solutions in plastics containers of the type used to present these products showed that thiomersal and chlorbutol appeared to be sorbed by these containers in contrast to benzalkonium chloride and chlorhexidine gluconate which interacted mainly by a surface adsorption process. The extent of any interactions was dependent upon the type of plastics material used to fabricate the container."}
{"id": "PMID:22617", "title": "The adhesion of film coatings to tablet surfaces--the effect of some direct compression excipients and lubricants.", "content": "The effect of some direct compression excipients and lubricants on the adhesion of hydroxypropyl methyl cellulose films has been examined using a specially designed tensile testing apparatus (Fisher & Rowe, 1976). The adhesion was found to be influenced by both the roughness, including microporosity, of the tablet surface and its polarity. Tablets prepared from microcrystalline cellulose showed very high adhesions despite having relatively smooth surfaces, owing to the surface being saturated with hydroxyl groups able to form hydrogen bonds with the corresponding groups on the polymer. The addition of magnesium or calcium stearate to the tablet was found to decrease the adhesion, but the addition of stearic acid caused a significant increase. The effect of lubricant concentration on the adhesion could be expressed by an equation similar to that proposed by Hofrichter & McLaren (1948) for the adhesion of vinyl chloride/vinyl acetate copolymers to regenerated cellulose.", "contents": "The adhesion of film coatings to tablet surfaces--the effect of some direct compression excipients and lubricants. The effect of some direct compression excipients and lubricants on the adhesion of hydroxypropyl methyl cellulose films has been examined using a specially designed tensile testing apparatus (Fisher & Rowe, 1976). The adhesion was found to be influenced by both the roughness, including microporosity, of the tablet surface and its polarity. Tablets prepared from microcrystalline cellulose showed very high adhesions despite having relatively smooth surfaces, owing to the surface being saturated with hydroxyl groups able to form hydrogen bonds with the corresponding groups on the polymer. The addition of magnesium or calcium stearate to the tablet was found to decrease the adhesion, but the addition of stearic acid caused a significant increase. The effect of lubricant concentration on the adhesion could be expressed by an equation similar to that proposed by Hofrichter & McLaren (1948) for the adhesion of vinyl chloride/vinyl acetate copolymers to regenerated cellulose."}
{"id": "PMID:22619", "title": "The effects of p-chlorophenylalanine and ethanolamine-O-sulphate in an animal test of anxiety.", "content": "p-Chlorophenylalanine, which produces a depletion of brain 5-HT concentration, had effects qualitatively similar to those previously found with chronic chlordiazepoxide and with acute ethanol in the social interaction test of anxiety. This result is compatible with the idea that a reduced turnover of 5-HT is important in anxiety reduction. On the same test, ethanolamine-O-sulphate, which raises brain gamma-aminobutyric acid, was without effect, suggesting raised concentrations of this acid are not essential for anxiety reduction.", "contents": "The effects of p-chlorophenylalanine and ethanolamine-O-sulphate in an animal test of anxiety. p-Chlorophenylalanine, which produces a depletion of brain 5-HT concentration, had effects qualitatively similar to those previously found with chronic chlordiazepoxide and with acute ethanol in the social interaction test of anxiety. This result is compatible with the idea that a reduced turnover of 5-HT is important in anxiety reduction. On the same test, ethanolamine-O-sulphate, which raises brain gamma-aminobutyric acid, was without effect, suggesting raised concentrations of this acid are not essential for anxiety reduction."}
{"id": "PMID:22621", "title": "Renal clearance procedure for the rat: effect of dopamine and standard saluretics.", "content": "Four standard diuretic compounds were evaluated for electrolyte output, effects on glomerular filtration rate (GFR), and effective renal plasma flow (RPF) in an anaesthetized rat preparation. Triamterene, hydrochlorothiazide, acetazoleamide and furosemide exerted their characteristic diuretic effects at doses which did not significantly change GFR or RPF. Regulation of the rate of a 3% mannitol-0.9% NaCl infusion to rats permitted the establishment of GFR and RPF values which were approximately in the middle of the reported range for this species. A significant increase in RPF without a concurrent rise in GFR was produced with dopamine. This was effectively blocked by the peripheral dopamine inhibitor, bulbocapnine.", "contents": "Renal clearance procedure for the rat: effect of dopamine and standard saluretics. Four standard diuretic compounds were evaluated for electrolyte output, effects on glomerular filtration rate (GFR), and effective renal plasma flow (RPF) in an anaesthetized rat preparation. Triamterene, hydrochlorothiazide, acetazoleamide and furosemide exerted their characteristic diuretic effects at doses which did not significantly change GFR or RPF. Regulation of the rate of a 3% mannitol-0.9% NaCl infusion to rats permitted the establishment of GFR and RPF values which were approximately in the middle of the reported range for this species. A significant increase in RPF without a concurrent rise in GFR was produced with dopamine. This was effectively blocked by the peripheral dopamine inhibitor, bulbocapnine."}
{"id": "PMID:22622", "title": "Effect of drugs on rats exposed to cold--restraint stress.", "content": "The extent of protection afforded by over 40 drugs of various pharmacological groups against the development of gastric erosions induced in rats by a combination of cold and restraint has been investigated. Some drugs offered good protection, others had no effect on, or exacerbated, the lesions. Attempts are made to explain the mode of action of the protective drugs.", "contents": "Effect of drugs on rats exposed to cold--restraint stress. The extent of protection afforded by over 40 drugs of various pharmacological groups against the development of gastric erosions induced in rats by a combination of cold and restraint has been investigated. Some drugs offered good protection, others had no effect on, or exacerbated, the lesions. Attempts are made to explain the mode of action of the protective drugs."}
{"id": "PMID:22623", "title": "Effects of pulmonary metabolites of prostaglandins E2 and F2alpha on guinea-pig respiratory tract.", "content": "The effects of three pulmonary metabolites of prostaglandins E2 and F2alpha on the guinea-pig tracheal muscle in vitro and on lung resistance in vivo were investigated. Prostaglandin F2alpha, 13,14-dihydro PGF2alpha and 13,14-dihydro 15-oxo PGF2alpha produced contractions on the tracheal muscle in vitro. 15-oxo PGF2alpha relaxed some tracheal preparations but stimulated others, the stimulant action having a threshold dose range some 10-25 times lower than the relaxant doses. Prostaglandin F2alpha and 13,14-dihydro PGF2alpha increased lung resistance in anaesthetized guinea-pigs. Prostaglandin E2 and its three pulmonary metabolites produced relaxation of guinea pig trachea in vitro and decreased lung resistance in vivo. All three metabolites were less active than PGE2 in both the systems. The in vitro effects of PGF2alpha and its metabolites were selectively blocked by polyphloretin phosphate.", "contents": "Effects of pulmonary metabolites of prostaglandins E2 and F2alpha on guinea-pig respiratory tract. The effects of three pulmonary metabolites of prostaglandins E2 and F2alpha on the guinea-pig tracheal muscle in vitro and on lung resistance in vivo were investigated. Prostaglandin F2alpha, 13,14-dihydro PGF2alpha and 13,14-dihydro 15-oxo PGF2alpha produced contractions on the tracheal muscle in vitro. 15-oxo PGF2alpha relaxed some tracheal preparations but stimulated others, the stimulant action having a threshold dose range some 10-25 times lower than the relaxant doses. Prostaglandin F2alpha and 13,14-dihydro PGF2alpha increased lung resistance in anaesthetized guinea-pigs. Prostaglandin E2 and its three pulmonary metabolites produced relaxation of guinea pig trachea in vitro and decreased lung resistance in vivo. All three metabolites were less active than PGE2 in both the systems. The in vitro effects of PGF2alpha and its metabolites were selectively blocked by polyphloretin phosphate."}
{"id": "PMID:22624", "title": "Identification of the in vitro N-oxidized metabolites of (+)- and (-)-N-benzylamphetamine.", "content": "This study has identified (+)- and (-)-N-benzyl-N-hydroxyamphetamine as metabolites after incubation of both (+)- and (-)-N-benzylamphetamine with fortified rabbit liver homogenates. The isomeric hydroxylamine metabolites were identified using the techniques of g.l.c., t.l.c. and combined g.l.c.-mass spectrometry (ms) and by comparison with results from reference samples. An additional novel metabolic product was identified after incubation of N-benzylamphetamine which had properties consistent with that of N-benzyl-amphetamine nitrone.", "contents": "Identification of the in vitro N-oxidized metabolites of (+)- and (-)-N-benzylamphetamine. This study has identified (+)- and (-)-N-benzyl-N-hydroxyamphetamine as metabolites after incubation of both (+)- and (-)-N-benzylamphetamine with fortified rabbit liver homogenates. The isomeric hydroxylamine metabolites were identified using the techniques of g.l.c., t.l.c. and combined g.l.c.-mass spectrometry (ms) and by comparison with results from reference samples. An additional novel metabolic product was identified after incubation of N-benzylamphetamine which had properties consistent with that of N-benzyl-amphetamine nitrone."}
{"id": "PMID:22717", "title": "Temperature dependence of the disintegration times of compressed tablets containing hydroxypropylcellulose as binder.", "content": "The dependence of the disintegration times of placebo and active tablets containing hydroxypropylcellulose (HPC), as binder on the temperature of the test medium in the region of 37 degrees is reported. The degree of temperature dependence varied with the HPC lot and concentration in the formulation of certain drugs, such as caffeine. The extent of the temperature dependence could be diminished by reducing the HPC concentration in the formulations. Corresponding trends were observed in drug release behaviour from some of these formulations. The effects observed were interpreted in terms of the thermodynamic behaviour of HPC systems and a specific drug-HPC interaction.", "contents": "Temperature dependence of the disintegration times of compressed tablets containing hydroxypropylcellulose as binder. The dependence of the disintegration times of placebo and active tablets containing hydroxypropylcellulose (HPC), as binder on the temperature of the test medium in the region of 37 degrees is reported. The degree of temperature dependence varied with the HPC lot and concentration in the formulation of certain drugs, such as caffeine. The extent of the temperature dependence could be diminished by reducing the HPC concentration in the formulations. Corresponding trends were observed in drug release behaviour from some of these formulations. The effects observed were interpreted in terms of the thermodynamic behaviour of HPC systems and a specific drug-HPC interaction."}
{"id": "PMID:22718", "title": "A model for short term drug absorption studies; comparison of sulphadiazine tablets.", "content": "The four parameter equation, applicable to drug absorption kinetics over a limited time period, has been used to interpret plasma concentration, time results following oral dosage with three different formulations of sulphadiazine tablets, to each of five subjects. Assessment parameters for the formulations, the time for ten percent absorption, the time interval between 10-90% absorption and the plasma concentration with no disposition (relative availability) have been estimated. Intersubject variation obscured many of the differences between formulations. To blank off this variation, plasma concentrations at each time were averaged and then random variation corresponding to the error of the assay method was applied so as to generate a number of sets of data which including the mean concentrations was equal to the number of sets in the original measurements. Kinetic analysis of these sets indicated a number of significant differences between the formulations.", "contents": "A model for short term drug absorption studies; comparison of sulphadiazine tablets. The four parameter equation, applicable to drug absorption kinetics over a limited time period, has been used to interpret plasma concentration, time results following oral dosage with three different formulations of sulphadiazine tablets, to each of five subjects. Assessment parameters for the formulations, the time for ten percent absorption, the time interval between 10-90% absorption and the plasma concentration with no disposition (relative availability) have been estimated. Intersubject variation obscured many of the differences between formulations. To blank off this variation, plasma concentrations at each time were averaged and then random variation corresponding to the error of the assay method was applied so as to generate a number of sets of data which including the mean concentrations was equal to the number of sets in the original measurements. Kinetic analysis of these sets indicated a number of significant differences between the formulations."}
{"id": "PMID:22719", "title": "Degradation of (--)-ephedrine in solution and during extraction with diethyl ether.", "content": "Significant losses occurred during the extraction of small quantities of ephedrine from aqueous media using either regular or analytical grades of diethyl ether. The losses were, at least in part, caused by reaction of the ephedrine with aldehydic impurities in the ether; three substituted oxazolidines were identified, using g.l.c. and g.l.c-ms. These and one other oxazolidine were synthesized and characterized by g.l.c., g.l.c.-ms, nmr and infrared spectroscopy. Alternative mechanisms for ephedrine breakdown were considered. Ephedrine was separately oxidized by three different oxidizing agents and also irradiated by ultraviolet light; the products were characterized by g.l.c., g.l.c.-ms. A method for the purification of diethyl ether is recommended to minimize ephedrine breakdown.", "contents": "Degradation of (--)-ephedrine in solution and during extraction with diethyl ether. Significant losses occurred during the extraction of small quantities of ephedrine from aqueous media using either regular or analytical grades of diethyl ether. The losses were, at least in part, caused by reaction of the ephedrine with aldehydic impurities in the ether; three substituted oxazolidines were identified, using g.l.c. and g.l.c-ms. These and one other oxazolidine were synthesized and characterized by g.l.c., g.l.c.-ms, nmr and infrared spectroscopy. Alternative mechanisms for ephedrine breakdown were considered. Ephedrine was separately oxidized by three different oxidizing agents and also irradiated by ultraviolet light; the products were characterized by g.l.c., g.l.c.-ms. A method for the purification of diethyl ether is recommended to minimize ephedrine breakdown."}
{"id": "PMID:22720", "title": "Red cell cyanide.", "content": "The amount of cyanide released on acidifying whole blood was much greater than the total from the plasma and red cells assayed separately, and varied directly with plasma thiocyanate concentrations. This artifactual formation of cyanide by whole blood was reduced by exposure to carbon monoxide. Incubation of haemolysates of washed red blood cells showed that optimum cyanide production from thiocyanate occurred at pH 4.5 with none at pH 7.4; spectrophotometric study confirmed the involvement of haemoglobin. It is doubtful whether this activity of haemoglobin is of normal physiological importance and it is probable that the evidence for the enzyme, 'thiocyanate oxidase' was based on this artifact of assay. Plasma cyanide is probably the metabolically relevant measurement, since the red blood cells act as a 'cyanide sink'. Where values for whole blood cyanide are required we recommend separate assay of plasma and saline washed red blood cells.", "contents": "Red cell cyanide. The amount of cyanide released on acidifying whole blood was much greater than the total from the plasma and red cells assayed separately, and varied directly with plasma thiocyanate concentrations. This artifactual formation of cyanide by whole blood was reduced by exposure to carbon monoxide. Incubation of haemolysates of washed red blood cells showed that optimum cyanide production from thiocyanate occurred at pH 4.5 with none at pH 7.4; spectrophotometric study confirmed the involvement of haemoglobin. It is doubtful whether this activity of haemoglobin is of normal physiological importance and it is probable that the evidence for the enzyme, 'thiocyanate oxidase' was based on this artifact of assay. Plasma cyanide is probably the metabolically relevant measurement, since the red blood cells act as a 'cyanide sink'. Where values for whole blood cyanide are required we recommend separate assay of plasma and saline washed red blood cells."}
{"id": "PMID:22721", "title": "Changes in muscarinic ligand binding to intestinal muscle strips produced by pre-exposure to hypotonic conditions.", "content": "The extent of the binding of [3H]propylbenzilylcholine mustard (3H-PrBCM) to muscarinic receptors in longitudinal muscle strips from guinea-pig small intestine is increased by nearly 50% when the strips are preexposed to distilled water before measurement of 3H-PrBCM binding in Krebs-Henseleit solution. The apparent rate constant for 3H-PrBCM-receptor complex formation is more than double that of intact strips. The curves for the inhibition of 3H-PrBCM binding by methylatropinium bromide in normal and treated strips are superimposable, but, in contrast, distilled water pretreatment shifts the inhibition curve for carbachol to lower concentrations by a factor of 5-6. The inhibition curve for methylfurmethide is also shifted, by a factor of approximately 4, but the effect on the curve for hexyltrimethylammonium (C6TMA) is slight. The relative inhibition produced by benzhexol in the two preparations was variable. Comparison of the rate of equilibration of benzhexol with muscarinic receptors in intact and in distilled water pretreated muscle indicates that this inconsistency is unlikely to be due to incomplete equilibration.", "contents": "Changes in muscarinic ligand binding to intestinal muscle strips produced by pre-exposure to hypotonic conditions. The extent of the binding of [3H]propylbenzilylcholine mustard (3H-PrBCM) to muscarinic receptors in longitudinal muscle strips from guinea-pig small intestine is increased by nearly 50% when the strips are preexposed to distilled water before measurement of 3H-PrBCM binding in Krebs-Henseleit solution. The apparent rate constant for 3H-PrBCM-receptor complex formation is more than double that of intact strips. The curves for the inhibition of 3H-PrBCM binding by methylatropinium bromide in normal and treated strips are superimposable, but, in contrast, distilled water pretreatment shifts the inhibition curve for carbachol to lower concentrations by a factor of 5-6. The inhibition curve for methylfurmethide is also shifted, by a factor of approximately 4, but the effect on the curve for hexyltrimethylammonium (C6TMA) is slight. The relative inhibition produced by benzhexol in the two preparations was variable. Comparison of the rate of equilibration of benzhexol with muscarinic receptors in intact and in distilled water pretreated muscle indicates that this inconsistency is unlikely to be due to incomplete equilibration."}
{"id": "PMID:22722", "title": "Modification by monoamine oxidase inhibitors of the analgesic, hypothermic and toxic actions of morphine and pethidine in mice.", "content": "A single injection of phenelzine 100 mg kg-1 given 18 h before, decreased the analgesia and hypothermia induced by morphine, but potentiated the analgesic and hypothermic effects of pethidine, when the analgesics were administered either intraperitoneally, or intracerebroventricularly. The modification of pethidine analgesia and hypothermia, but not morphine analgesia, was antagonized by methysergide (10 mg lg-1, s.c.). The LD50 of pethidine, but not that of morphine, was 30-40% lower in mice treated with phenelzine tranylcypromine or iproniazid 6 h before the test. The increased lethality of a single dose of pethidine induced by phenelzine was also prevented by methysergide. Pretreatment of mice with 100 mg kg-1 phenelzine was followed by a significant rise in both brain tryptophan and 5-hydroxytryptamine (5-HT) concentrations which lasted for 24 h. Therefore, the changes in pethidine effects could have been due to raised brain tryptophan and 5-HT concentrations.", "contents": "Modification by monoamine oxidase inhibitors of the analgesic, hypothermic and toxic actions of morphine and pethidine in mice. A single injection of phenelzine 100 mg kg-1 given 18 h before, decreased the analgesia and hypothermia induced by morphine, but potentiated the analgesic and hypothermic effects of pethidine, when the analgesics were administered either intraperitoneally, or intracerebroventricularly. The modification of pethidine analgesia and hypothermia, but not morphine analgesia, was antagonized by methysergide (10 mg lg-1, s.c.). The LD50 of pethidine, but not that of morphine, was 30-40% lower in mice treated with phenelzine tranylcypromine or iproniazid 6 h before the test. The increased lethality of a single dose of pethidine induced by phenelzine was also prevented by methysergide. Pretreatment of mice with 100 mg kg-1 phenelzine was followed by a significant rise in both brain tryptophan and 5-hydroxytryptamine (5-HT) concentrations which lasted for 24 h. Therefore, the changes in pethidine effects could have been due to raised brain tryptophan and 5-HT concentrations."}
{"id": "PMID:22723", "title": "Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis.", "content": "Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of non-specific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1.11 mg kg-1; the ED50 increased linearly to 115 mg kg-1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil.", "contents": "Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis. Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of non-specific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1.11 mg kg-1; the ED50 increased linearly to 115 mg kg-1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil."}
{"id": "PMID:22731", "title": "Particle slippage and rearrangement during compression of pharmaceutical powders.", "content": "Compression data from different size fractions of lactose, chloroquine diphosphate, stearic acid and calcium carbonate have been analysed using the Walker and the Heckel compression equations. Points of inflection in graphs of log applied pressure vs the reciprocal of the packing fraction at low pressures corresponded closely to figures for theoretical packing conditions for equisized spheres and are attributed to a change in the stage of compression. The degree of particle slippage and rearrangement taking place during compression has been shown to increase as the particle size of the powder decreases and to be more extensive for powders composed of non-spherical particles. In addition, three types of compression behaviour have been distinguished for the four powders studied.", "contents": "Particle slippage and rearrangement during compression of pharmaceutical powders. Compression data from different size fractions of lactose, chloroquine diphosphate, stearic acid and calcium carbonate have been analysed using the Walker and the Heckel compression equations. Points of inflection in graphs of log applied pressure vs the reciprocal of the packing fraction at low pressures corresponded closely to figures for theoretical packing conditions for equisized spheres and are attributed to a change in the stage of compression. The degree of particle slippage and rearrangement taking place during compression has been shown to increase as the particle size of the powder decreases and to be more extensive for powders composed of non-spherical particles. In addition, three types of compression behaviour have been distinguished for the four powders studied."}
{"id": "PMID:22737", "title": "Solid dispersions of nitrofurantoin, ethotoin, and coumarin with polyethylene glycol 6000 and their coprecipitates with providone 25,000.", "content": "The influence of two linear polymers, polyethylene glycol 6000 and povidone 25,000, on the dissolution rate of three poorly soluble drugs, nitrofurantoin, ethotoin, and coumarin, was studied. Povidone 25,000 produced better drug solubilization than polyethylene glycol 6000 with the drug-polymer ratios studied, and an increase in the weight fraction of either polymer gave more rapid dissolution. TLC and IR studies ruled out any interaction between the drugs and polyethylene glycol 6000. IR spectrophotometry provided evidence that there was complex formation between nitrofurantoin and povidone 25,000, probably via hydrogen bonding.", "contents": "Solid dispersions of nitrofurantoin, ethotoin, and coumarin with polyethylene glycol 6000 and their coprecipitates with providone 25,000. The influence of two linear polymers, polyethylene glycol 6000 and povidone 25,000, on the dissolution rate of three poorly soluble drugs, nitrofurantoin, ethotoin, and coumarin, was studied. Povidone 25,000 produced better drug solubilization than polyethylene glycol 6000 with the drug-polymer ratios studied, and an increase in the weight fraction of either polymer gave more rapid dissolution. TLC and IR studies ruled out any interaction between the drugs and polyethylene glycol 6000. IR spectrophotometry provided evidence that there was complex formation between nitrofurantoin and povidone 25,000, probably via hydrogen bonding."}
{"id": "PMID:22738", "title": "General method for determining macrodissociation constants of polyprotic, amphoteric compounds from solubility measurements.", "content": "Equilibrium solubility and pH measurements can be used to determine macrodissociation constants of weak acids and bases of some highly insoluble substances. Equations are derived extending solubility, pH, and pKa (macroscopic) relationships to polyprotic, amphoteric substances. A general method for estimating pKa values, given a set of solubility and pH measurements, is presented. Included in the estimation procedure is a subroutine for approximating thermodynamic pKa values. The method was tested on two data sets (tyrosine and 2,3-dihydroxyadenine) and rendered pKa (thermodynamic) estimates in close agreement with those using other methods.", "contents": "General method for determining macrodissociation constants of polyprotic, amphoteric compounds from solubility measurements. Equilibrium solubility and pH measurements can be used to determine macrodissociation constants of weak acids and bases of some highly insoluble substances. Equations are derived extending solubility, pH, and pKa (macroscopic) relationships to polyprotic, amphoteric substances. A general method for estimating pKa values, given a set of solubility and pH measurements, is presented. Included in the estimation procedure is a subroutine for approximating thermodynamic pKa values. The method was tested on two data sets (tyrosine and 2,3-dihydroxyadenine) and rendered pKa (thermodynamic) estimates in close agreement with those using other methods."}
{"id": "PMID:22739", "title": "l-Bunolol and propranolol: oral and intravenous beta-adrenoceptor blocking activity in rats compared to dogs and humans.", "content": "To determine the pharmacological significance of reported differences between species in l-bunolol metabolism, oral and intravenous beta-adrenoceptor blocking activity against an isoproterenol-induced tachycardia was compared in dogs, rats, and humans. Propranolol was similarly studied in rats and dogs. Species differences in intravenous potency were minimal for both compounds in contrast to oral dose studies. Oral to intravenous ratios of doses causing a comparable degree of beta-adrenoceptor blockade after l-bunolol were: rat, 212; dog 4; and human, 5. For propranolol, the oral to intravenous dose ratios were 210 and 32 for the rat and dog, respectively. These pharmacological findings show major differences in the rat compared to dogs and humans and may be explained in part by differences in the urinary excretion patterns of l-bunolol in the various species.", "contents": "l-Bunolol and propranolol: oral and intravenous beta-adrenoceptor blocking activity in rats compared to dogs and humans. To determine the pharmacological significance of reported differences between species in l-bunolol metabolism, oral and intravenous beta-adrenoceptor blocking activity against an isoproterenol-induced tachycardia was compared in dogs, rats, and humans. Propranolol was similarly studied in rats and dogs. Species differences in intravenous potency were minimal for both compounds in contrast to oral dose studies. Oral to intravenous ratios of doses causing a comparable degree of beta-adrenoceptor blockade after l-bunolol were: rat, 212; dog 4; and human, 5. For propranolol, the oral to intravenous dose ratios were 210 and 32 for the rat and dog, respectively. These pharmacological findings show major differences in the rat compared to dogs and humans and may be explained in part by differences in the urinary excretion patterns of l-bunolol in the various species."}
{"id": "PMID:22740", "title": "Stability of tetrahydrocannabinols II.", "content": "The biphasic degradation of delta9-tetrahydrocannabinol (I), as monitored by flame-ionization GLC, produced delta8-tetrahydrocannabinol (II), cannabidiol (X), 9-hydroxyhexahydrocannabinol (VI), 9,10-dihydro-9-hydroxyisocannabidiol (VI), and and 6,12-dihydro-6-hydroxycannabidiol (VIII) in acidic solutions. Further identification was made by GLC, mass spectrometry, and comparison with authentic samples. Only II and IV were produced above pH 4 in the neutral region by first-order kinetics. The acidic degradation of cannabidiol (X) gave I and the products of the acidic degradation of I. The initial phase of acidic I degradation was assigned to the development of solvolytic equilibria among I, VIII, X, and, possibly, isocannabidiol (IX), with the concomitant production of II and IV. Compounds VIII, IX, and X did not appear in the neutral region since ether cleavage occurred only in strong mineral acids. Hydration of the delta9-double bond resulted only in acid-catalyzed equilibria of cleaved ethers with the delta8-configurations and characterized the second phase of acid degradation of I. Cannabinol and hexahydrocannabinol were found together in several cases due to the disproportionation of I as catalyzed by silicic acid, silica gel, and chloroform.", "contents": "Stability of tetrahydrocannabinols II. The biphasic degradation of delta9-tetrahydrocannabinol (I), as monitored by flame-ionization GLC, produced delta8-tetrahydrocannabinol (II), cannabidiol (X), 9-hydroxyhexahydrocannabinol (VI), 9,10-dihydro-9-hydroxyisocannabidiol (VI), and and 6,12-dihydro-6-hydroxycannabidiol (VIII) in acidic solutions. Further identification was made by GLC, mass spectrometry, and comparison with authentic samples. Only II and IV were produced above pH 4 in the neutral region by first-order kinetics. The acidic degradation of cannabidiol (X) gave I and the products of the acidic degradation of I. The initial phase of acidic I degradation was assigned to the development of solvolytic equilibria among I, VIII, X, and, possibly, isocannabidiol (IX), with the concomitant production of II and IV. Compounds VIII, IX, and X did not appear in the neutral region since ether cleavage occurred only in strong mineral acids. Hydration of the delta9-double bond resulted only in acid-catalyzed equilibria of cleaved ethers with the delta8-configurations and characterized the second phase of acid degradation of I. Cannabinol and hexahydrocannabinol were found together in several cases due to the disproportionation of I as catalyzed by silicic acid, silica gel, and chloroform."}
{"id": "PMID:22741", "title": "The pH of brain extracellular fluid in the cat.", "content": "1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface.2. The pH of extracellular fluid (pH(e.c.f.)) was measured with pH microelectrodes of tip size 1-3 mum in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose-urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge.3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0.03 and 0.08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex.4. When plasma P(CO2) was altered, pH(e.c.f.) changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pH(e.c.f.) coincided with changes in ventilation. Changes in pH(c.s.f.) over the same areas were invariably slower.5. CO(2) buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2.2, -2.1 and -1.6.6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO(3)-. Only up to a depth of 1 mm beneath the surface was pH(e.c.f.) affected by superfusion of mock c.s.f. in the range 6.8-8.0 units. This response had a latent period of 2-3 min and was complete in 15 min.7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pH(e.c.f.) was markedly affected by changes of blood pressure.8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pH(e.c.f.) is more obviously affected by changes in P(a, CO2) than pH(c.s.f.) and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected.", "contents": "The pH of brain extracellular fluid in the cat. 1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface.2. The pH of extracellular fluid (pH(e.c.f.)) was measured with pH microelectrodes of tip size 1-3 mum in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose-urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge.3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0.03 and 0.08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex.4. When plasma P(CO2) was altered, pH(e.c.f.) changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pH(e.c.f.) coincided with changes in ventilation. Changes in pH(c.s.f.) over the same areas were invariably slower.5. CO(2) buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2.2, -2.1 and -1.6.6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO(3)-. Only up to a depth of 1 mm beneath the surface was pH(e.c.f.) affected by superfusion of mock c.s.f. in the range 6.8-8.0 units. This response had a latent period of 2-3 min and was complete in 15 min.7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pH(e.c.f.) was markedly affected by changes of blood pressure.8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pH(e.c.f.) is more obviously affected by changes in P(a, CO2) than pH(c.s.f.) and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected."}
{"id": "PMID:22746", "title": "Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation.", "content": "1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected. 2. NA output was doubled at low concentrations (0.1--0.3 mM) of 4-AP, but maximal effect was obtained at 1--3 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium-Krebs solution were markedly enhanced by 4-AP. 4-AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 4. 4-AP at pH 8.5 was more effective in enhancing NA release than at pH 7.4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47%. 6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh). 7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA.", "contents": "Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation. 1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected. 2. NA output was doubled at low concentrations (0.1--0.3 mM) of 4-AP, but maximal effect was obtained at 1--3 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium-Krebs solution were markedly enhanced by 4-AP. 4-AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 4. 4-AP at pH 8.5 was more effective in enhancing NA release than at pH 7.4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47%. 6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh). 7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA."}
{"id": "PMID:22748", "title": "Pyrazolodiazepines. 2. 4-Aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones as antianxiety and anticonvulsant agents.", "content": "A series of 4-aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones was synthesized and screened for psychotropic activity. In animals, a number of these pyrazolodiazepinones had strong CNS effects similar to diazepam. One compound, 4-(2-fluorophenyl)-6,8-dihydro-1,3,8-trimethylpyrazolo[3,4-e] [1,4]diazepin-7(1H)-one (54), is being studied in the clinic as a component of a new animal anesthetic, Tilazol.", "contents": "Pyrazolodiazepines. 2. 4-Aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones as antianxiety and anticonvulsant agents. A series of 4-aryl-1,3-dialkyl-6,8-dihydropyrazolo[3,4-e] [1,4]diazepin-7(1H)-ones was synthesized and screened for psychotropic activity. In animals, a number of these pyrazolodiazepinones had strong CNS effects similar to diazepam. One compound, 4-(2-fluorophenyl)-6,8-dihydro-1,3,8-trimethylpyrazolo[3,4-e] [1,4]diazepin-7(1H)-one (54), is being studied in the clinic as a component of a new animal anesthetic, Tilazol."}
{"id": "PMID:22749", "title": "Synthetic models of deoxyribonucleic acid complexes with antimalarial compounds. 3. Forces involved in the stacking interaction between aminoquinoline and the nucleotide bases.", "content": "As an approach to the problem of the nature of the forces responsible for the stacking interactions between the aminoquinoline ring of the antimalarial chloroquine and the monomeric nucleotide bases, we have examined models in which the aromatic nucleus of the drug is linked to the nucleotide bases by a trimethylene chain. The degree of stacking of the models was determined in different conditions of solvent, pH, and temperature by hypochromism measurement in the UV. The results show that forces of the donor-acceptor type, due to the presence of a positive charge on the quinoline ring at neutral pH, do not bring an important contribution to the stacking interaction between the aminoquinoline and the nucleotide bases, while the influence of the solvent water is fundamental.", "contents": "Synthetic models of deoxyribonucleic acid complexes with antimalarial compounds. 3. Forces involved in the stacking interaction between aminoquinoline and the nucleotide bases. As an approach to the problem of the nature of the forces responsible for the stacking interactions between the aminoquinoline ring of the antimalarial chloroquine and the monomeric nucleotide bases, we have examined models in which the aromatic nucleus of the drug is linked to the nucleotide bases by a trimethylene chain. The degree of stacking of the models was determined in different conditions of solvent, pH, and temperature by hypochromism measurement in the UV. The results show that forces of the donor-acceptor type, due to the presence of a positive charge on the quinoline ring at neutral pH, do not bring an important contribution to the stacking interaction between the aminoquinoline and the nucleotide bases, while the influence of the solvent water is fundamental."}
{"id": "PMID:22750", "title": "beta-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols.", "content": "The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.", "contents": "beta-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols. The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed."}
{"id": "PMID:22751", "title": "Synthesis and beta-adrenergic blocking activity of a novel class of aromatic oxime ethers.", "content": "A new series of beta-adrenergic blocking amines containing an oximino-propanolic chain linked to an aromatic nucleus was synthesized. Most of the derivatives are characterized by beta2-selectivity. The structure-activity relationship are discussed. One of the compounds, selected for further studies, was more active on the trachea than on the atria of guinea pig, 155 times in vitro and 26 times in vivo. In comparison, butoxamine's beta2-selectivity is 13 in vitro and only 2 in vivo. With a series of 30 acetophenone oxime derivatives, no quantitative structure-activity relationships could be detected.", "contents": "Synthesis and beta-adrenergic blocking activity of a novel class of aromatic oxime ethers. A new series of beta-adrenergic blocking amines containing an oximino-propanolic chain linked to an aromatic nucleus was synthesized. Most of the derivatives are characterized by beta2-selectivity. The structure-activity relationship are discussed. One of the compounds, selected for further studies, was more active on the trachea than on the atria of guinea pig, 155 times in vitro and 26 times in vivo. In comparison, butoxamine's beta2-selectivity is 13 in vitro and only 2 in vivo. With a series of 30 acetophenone oxime derivatives, no quantitative structure-activity relationships could be detected."}
{"id": "PMID:22752", "title": "Synthesis of heteroaromatic potential beta-adrenergic antagonists by the glycidol route.", "content": "The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity.", "contents": "Synthesis of heteroaromatic potential beta-adrenergic antagonists by the glycidol route. The synthesis of several 3-alkylamino-2-hydroxypropyl heteroaryl ethers (13-15, 17, and 18) is described. These compounds were prepared by the alkylamination of the corresponding glycidyl ethers (6-8, 10, and 11), which in turn were obtained from the requisite heteroaryl halides and the sodium salt of glycidol. The above basic ethers exhibited beta-blocking activity, but the potency of the tested compounds was considerably less than that of propanolol. Only 3-tert-butylamino-2-hydroxyl-1-(1,2,4-thiadiazol-5-yl) propyl ether (13) showed some selective myocardial beta-blocking activity."}
{"id": "PMID:22753", "title": "(1-(3-(Phenothiazin-10-yl)propyl)-4-piperidinyl)phenylmethanones, a novel class of long-acting neuroleptic agents.", "content": "In previous studies the phenyl-4-piperidinylmethanone moiety was shown to be a neuroleptic pharmacophore. A short series of [1-[3-(phenothiazin-10-yl)propyl]-4-piperidinyl]phenylmethanones was prepared and tested for neuroleptic activity using the blockade of d-amphetamine lethality in aggregated mice and suppression of conditioned avoidance behavior as the end points. Most compounds were shown to be potent neuroleptic agents and two were found to possess a long duration of action.", "contents": "(1-(3-(Phenothiazin-10-yl)propyl)-4-piperidinyl)phenylmethanones, a novel class of long-acting neuroleptic agents. In previous studies the phenyl-4-piperidinylmethanone moiety was shown to be a neuroleptic pharmacophore. A short series of [1-[3-(phenothiazin-10-yl)propyl]-4-piperidinyl]phenylmethanones was prepared and tested for neuroleptic activity using the blockade of d-amphetamine lethality in aggregated mice and suppression of conditioned avoidance behavior as the end points. Most compounds were shown to be potent neuroleptic agents and two were found to possess a long duration of action."}
{"id": "PMID:22754", "title": "Potential inhibitors of L-asparagine biosynthesis. 4. Substituted sulfonamide and sulfonylhydrazide analogues of L-asparagine.", "content": "Several N-substituted sulfonamides and N'-substituted sulfonylhydrazides have been prepared as sulfur analogues of L-asparagine with the potential of acting as inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma). L-Cysteine was converted in known steps to N-carboxy-3-(sulfonylchloro)-L-alanine dibenzyl ester (1). Condensation of 1 with O-benzylhydroxylamine, p-(fluorosulfonyl)benzylamine, or monoethyl fumarylhydrazide (9), followed by deblocking with HF, gave 3-(hydroxysulfamoyl)-L-alanine (3a), 3-[p-(fluorosulfonylbenzyl)]sulfamoyl-L-alanine (3c), and 3-sulfo-L-alanine S-[2-[(E)-3-(ethoxycarbonyl)acryloyl]hydrazide] (3e), respectively. Similarly, 1 with 2-chloroethylamine and deblocking with H2-Pd gave 3-[(2-chloroethyl)sulfamoyl]-L-alanine (3b). tert-Butyl carbazate was allowed to react with 1 and the tert-butyl group was removed with HCl. The resulting sulfonylhydrazide 7 was condensed with p-(fluorosulfonyl)benzoyl chloride and then deblocked with HF to give 3-sulfo-L-alanine S-[2-[P-(fluorosulfonyl)benzoyl]hydrazide] (3d). The inhibition of ASase by 3a-e at 2 mM was 97, 0, 30, 43, and 37%, respectively, and 3a was competitive with L-aspartic acid. Neither 3a nor 3e was effective in increasing the life span of mice bearing P-388 lymphocytic leukemia.", "contents": "Potential inhibitors of L-asparagine biosynthesis. 4. Substituted sulfonamide and sulfonylhydrazide analogues of L-asparagine. Several N-substituted sulfonamides and N'-substituted sulfonylhydrazides have been prepared as sulfur analogues of L-asparagine with the potential of acting as inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma). L-Cysteine was converted in known steps to N-carboxy-3-(sulfonylchloro)-L-alanine dibenzyl ester (1). Condensation of 1 with O-benzylhydroxylamine, p-(fluorosulfonyl)benzylamine, or monoethyl fumarylhydrazide (9), followed by deblocking with HF, gave 3-(hydroxysulfamoyl)-L-alanine (3a), 3-[p-(fluorosulfonylbenzyl)]sulfamoyl-L-alanine (3c), and 3-sulfo-L-alanine S-[2-[(E)-3-(ethoxycarbonyl)acryloyl]hydrazide] (3e), respectively. Similarly, 1 with 2-chloroethylamine and deblocking with H2-Pd gave 3-[(2-chloroethyl)sulfamoyl]-L-alanine (3b). tert-Butyl carbazate was allowed to react with 1 and the tert-butyl group was removed with HCl. The resulting sulfonylhydrazide 7 was condensed with p-(fluorosulfonyl)benzoyl chloride and then deblocked with HF to give 3-sulfo-L-alanine S-[2-[P-(fluorosulfonyl)benzoyl]hydrazide] (3d). The inhibition of ASase by 3a-e at 2 mM was 97, 0, 30, 43, and 37%, respectively, and 3a was competitive with L-aspartic acid. Neither 3a nor 3e was effective in increasing the life span of mice bearing P-388 lymphocytic leukemia."}
{"id": "PMID:22755", "title": "Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine.", "content": "A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.", "contents": "Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine. A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained."}
{"id": "PMID:22756", "title": "Adrenoceptor blocking agents. 2. 2-(alpha-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective beta2-adrenoceptor antagonists.", "content": "Threo- and erythro-2-(alpha-hydroxybenzyl)-3,3-dimethylaziridines (1a and 1b) and threo-2-[alpha-hydroxy(2-naphthyl)methyl]- and 2-[alpha-hydroxy(3,4-dichlorobenzyl)]-3,3-dimethylaziridines (1d and 1c) have been prepared as conformationally restricted analogues of beta-adrenoceptor blocking agents like dichloroisoproterenol (DCI) and pronethalol. The aziridine analogues 1 except possibly 1c are competitive antagonists of isoproterenol-induced response on a guinea pig tracheal chain preparation and the order of potency is 1d greater than 1a greater than or equal to 1b greater than propranolol greater than 1c. Unlike propranolol, these compounds have no effect on the isoproterenol-induced response on guinea pig auricles and no significant local anesthetic and antiarrhythmic activity. The aziridine analogues 1 represent the first of a new class of selective beta2-adrenoceptor blocking agents.", "contents": "Adrenoceptor blocking agents. 2. 2-(alpha-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective beta2-adrenoceptor antagonists. Threo- and erythro-2-(alpha-hydroxybenzyl)-3,3-dimethylaziridines (1a and 1b) and threo-2-[alpha-hydroxy(2-naphthyl)methyl]- and 2-[alpha-hydroxy(3,4-dichlorobenzyl)]-3,3-dimethylaziridines (1d and 1c) have been prepared as conformationally restricted analogues of beta-adrenoceptor blocking agents like dichloroisoproterenol (DCI) and pronethalol. The aziridine analogues 1 except possibly 1c are competitive antagonists of isoproterenol-induced response on a guinea pig tracheal chain preparation and the order of potency is 1d greater than 1a greater than or equal to 1b greater than propranolol greater than 1c. Unlike propranolol, these compounds have no effect on the isoproterenol-induced response on guinea pig auricles and no significant local anesthetic and antiarrhythmic activity. The aziridine analogues 1 represent the first of a new class of selective beta2-adrenoceptor blocking agents."}
{"id": "PMID:22757", "title": "Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants.", "content": "3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores.", "contents": "Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants. 3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores."}
{"id": "PMID:22758", "title": "Disseminated intravascular coagulopathy during experimental pneumococcal sepsis: studies in normal and asplenic rhesus monkeys.", "content": "Disseminated intravascular coagulation (DIC) was induced in both normal and asplenic rhesus monkeys by intravenous challenge with Streptococcus pneumoniae. Our observations in the infected monkeys have led us to conclude that (1) pneumococcal capsular polysaccharide (PCP), immune complexes and complement may not have primary roles in the initiation of DIC; (2) intact pneumococci may be catalysts for the development of DIC; (3) the initial event in DIC may be activation of Hageman factor; and (4) evidence of activation of Hageman factor-dependent systems is present regardless of severity of infection.", "contents": "Disseminated intravascular coagulopathy during experimental pneumococcal sepsis: studies in normal and asplenic rhesus monkeys. Disseminated intravascular coagulation (DIC) was induced in both normal and asplenic rhesus monkeys by intravenous challenge with Streptococcus pneumoniae. Our observations in the infected monkeys have led us to conclude that (1) pneumococcal capsular polysaccharide (PCP), immune complexes and complement may not have primary roles in the initiation of DIC; (2) intact pneumococci may be catalysts for the development of DIC; (3) the initial event in DIC may be activation of Hageman factor; and (4) evidence of activation of Hageman factor-dependent systems is present regardless of severity of infection."}
{"id": "PMID:22764", "title": "A sexual-enhancement workshop: beyond group systematic desensitization for women's sexual anxiety.", "content": "This study investigated whether six women who previously had received 15 sessions of group systematic desensitization (SD) for their sexual anxiety would report additional treatment gains from participation in a sexual-enhancement workshop with their partners. After group SD six couples participated in six, 1 1/2 hour weekly group sessions. The women reported a significant increase in marital adjustment and a significant decrease in sexual anxiety. A significant decrease was found in the women's sexual nonresponsiveness as perceived by their partners. Future studies should (1) contrast the effects of group SD with women alone versus couple group treatment, (2) determine which treatment components are most influential for defined subject types, and (3) obtain data on men's sexual functioning.", "contents": "A sexual-enhancement workshop: beyond group systematic desensitization for women's sexual anxiety. This study investigated whether six women who previously had received 15 sessions of group systematic desensitization (SD) for their sexual anxiety would report additional treatment gains from participation in a sexual-enhancement workshop with their partners. After group SD six couples participated in six, 1 1/2 hour weekly group sessions. The women reported a significant increase in marital adjustment and a significant decrease in sexual anxiety. A significant decrease was found in the women's sexual nonresponsiveness as perceived by their partners. Future studies should (1) contrast the effects of group SD with women alone versus couple group treatment, (2) determine which treatment components are most influential for defined subject types, and (3) obtain data on men's sexual functioning."}
{"id": "PMID:22766", "title": "Transcriptase activity associated with rabies virion.", "content": "Rabies virion-associated transcriptase activity was investigated in vitro and compared with that of the New Jersey serotype of vesicular stomatitis virus. The concentration of detergent that affected [3H]GMP incoporation into acid-insoluble material was significantly different for both viruses. Vesicular stomatitis virus New Jersey required 0.05 to 0.1% nonionic detergent, whereas rabies virion could not be fully activated unless 4 to 5% detergent was used. Other optimal conditions were as follows: 40 mM NaCl, 5 mM Mg2+, 40 mM Tris-hydrochloride (pH 7.4), 5 mM dithiothreitol, and 30 degrees C. The reaction required four nucleoside triphosphates. The initial rate of RNA synthesis by rabies virion enzyme was 140 pmol of GMP incorporated/mg of viral protein per h and linearly increased until about 8 h, with a slight initial lag phase. The enzyme activity that correlated with the content of L protein was highest when rabies virions were grown at 33 degrees C. The product was single-stranded RNA, which was complementary in base sequences to rabies viral RNA. Most of the RNA synthesized sedimented at 6-16S.", "contents": "Transcriptase activity associated with rabies virion. Rabies virion-associated transcriptase activity was investigated in vitro and compared with that of the New Jersey serotype of vesicular stomatitis virus. The concentration of detergent that affected [3H]GMP incoporation into acid-insoluble material was significantly different for both viruses. Vesicular stomatitis virus New Jersey required 0.05 to 0.1% nonionic detergent, whereas rabies virion could not be fully activated unless 4 to 5% detergent was used. Other optimal conditions were as follows: 40 mM NaCl, 5 mM Mg2+, 40 mM Tris-hydrochloride (pH 7.4), 5 mM dithiothreitol, and 30 degrees C. The reaction required four nucleoside triphosphates. The initial rate of RNA synthesis by rabies virion enzyme was 140 pmol of GMP incorporated/mg of viral protein per h and linearly increased until about 8 h, with a slight initial lag phase. The enzyme activity that correlated with the content of L protein was highest when rabies virions were grown at 33 degrees C. The product was single-stranded RNA, which was complementary in base sequences to rabies viral RNA. Most of the RNA synthesized sedimented at 6-16S."}
{"id": "PMID:22767", "title": "The increasing incidence of Ampicillin-resistant Haemophilus influenzae. A cause of otitis media.", "content": "Middle ear exudate was obtained by myringotomy or aspiration from 625 suburban children, aged 1 month to 12 years, who had acute otitis media; bacterial pathogens were isolated from 71%. Haemophilus species were isolated from 212 (29%), and Streptococcus pneumoniae from 205 (28%). From 1975 to August 1977, the number of Haemophilus isolates found to be resistant to ampicillin has appreciably increased. Currently, 8% of all cases of acute otitis media in the Washington, DC, area are due to H influenzae resistant to ampicillin. Thirty-one of 35 patients with resistant H influenzae otitis were treated with an erythromycin/sulfisoxazole combination with an impressive clinical response. Twenty-six of these 31 cases had failed to have H influenzae eradicated by an average of ten days of oral ampicillin in recommended doses.", "contents": "The increasing incidence of Ampicillin-resistant Haemophilus influenzae. A cause of otitis media. Middle ear exudate was obtained by myringotomy or aspiration from 625 suburban children, aged 1 month to 12 years, who had acute otitis media; bacterial pathogens were isolated from 71%. Haemophilus species were isolated from 212 (29%), and Streptococcus pneumoniae from 205 (28%). From 1975 to August 1977, the number of Haemophilus isolates found to be resistant to ampicillin has appreciably increased. Currently, 8% of all cases of acute otitis media in the Washington, DC, area are due to H influenzae resistant to ampicillin. Thirty-one of 35 patients with resistant H influenzae otitis were treated with an erythromycin/sulfisoxazole combination with an impressive clinical response. Twenty-six of these 31 cases had failed to have H influenzae eradicated by an average of ten days of oral ampicillin in recommended doses."}
{"id": "PMID:22768", "title": "Inhibition by cyanide of drug oxidations in rat liver microsomes.", "content": "Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in innhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed.", "contents": "Inhibition by cyanide of drug oxidations in rat liver microsomes. Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in innhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed."}
{"id": "PMID:22769", "title": "Impaired maturation of pre-synaptic cholinergic nerve terminals in the superior cervical ganglia after administration of guanethidine and dexamethasone.", "content": "The role of post-synaptic cells in the development of pre-synaptic cholinergic nerve terminals has been investigated in immature rat superior cervical ganglia (SCG) and adrenals employing chemical agents which prevent the normal maturation of post-synaptic cells. A marked atrophy of ganglion adrenergic neurons after guanethidine administration was accompanied by the complete failure of normal maturation of choline acetyltransferase (ChAc) activity in the presynaptic endings. However, the same treatment failed to alter the levels of ChAc in the mature ganglia despite the marked atrophy of adrenergic neurons. Administration of dexamethasone resulted in a growth retardation of ganglion neurons as well as adrenal chromaffin cells reflected by the lower levels of tyrosine hydroxylase and dopamine-beta-hydroxylase than those in untreated tissues. The levels of ChAc were significantly lower in the ganglia, but not in the adrenals when treatment was started immediately after birth. These results support the view that the normal synapse formation in the SCG depends on the normal maturation of adrenergic neurons, and suggest that this dependence is detectable only during a limited period of life.", "contents": "Impaired maturation of pre-synaptic cholinergic nerve terminals in the superior cervical ganglia after administration of guanethidine and dexamethasone. The role of post-synaptic cells in the development of pre-synaptic cholinergic nerve terminals has been investigated in immature rat superior cervical ganglia (SCG) and adrenals employing chemical agents which prevent the normal maturation of post-synaptic cells. A marked atrophy of ganglion adrenergic neurons after guanethidine administration was accompanied by the complete failure of normal maturation of choline acetyltransferase (ChAc) activity in the presynaptic endings. However, the same treatment failed to alter the levels of ChAc in the mature ganglia despite the marked atrophy of adrenergic neurons. Administration of dexamethasone resulted in a growth retardation of ganglion neurons as well as adrenal chromaffin cells reflected by the lower levels of tyrosine hydroxylase and dopamine-beta-hydroxylase than those in untreated tissues. The levels of ChAc were significantly lower in the ganglia, but not in the adrenals when treatment was started immediately after birth. These results support the view that the normal synapse formation in the SCG depends on the normal maturation of adrenergic neurons, and suggest that this dependence is detectable only during a limited period of life."}
{"id": "PMID:22771", "title": "Enhancement of NADPH-dependent lipid peroxidation activity by ethylene-diamineteraacetic acid (EDTA) in the presence of ferrous ion in rabbit liver microsomes.", "content": "The addition of EDTA to the incubation mixture containing rabbit liver microsomes and ferrous ion resulted in 2-fold increase of lipid peroxidation activity. Such an enhancement was not observed in rat liver microsomes. The maximum lipid peroxidation activity seen in rabbit microsomes in the presence of EDTA and ferrous ion was about 80% that seen in rat liver microsomes. From these results, it is likely that low lipid peroxidation activity in rabbit liver microsomes may account for the insufficiency of an EDTA-LIKE FACTORS(S) IN RABBIT LIVER MICROSOMES.", "contents": "Enhancement of NADPH-dependent lipid peroxidation activity by ethylene-diamineteraacetic acid (EDTA) in the presence of ferrous ion in rabbit liver microsomes. The addition of EDTA to the incubation mixture containing rabbit liver microsomes and ferrous ion resulted in 2-fold increase of lipid peroxidation activity. Such an enhancement was not observed in rat liver microsomes. The maximum lipid peroxidation activity seen in rabbit microsomes in the presence of EDTA and ferrous ion was about 80% that seen in rat liver microsomes. From these results, it is likely that low lipid peroxidation activity in rabbit liver microsomes may account for the insufficiency of an EDTA-LIKE FACTORS(S) IN RABBIT LIVER MICROSOMES."}
{"id": "PMID:22774", "title": "[Psychotropic drugs--real progress or danger? (author's transl)].", "content": "Three types of modern psychotropic drugs strongly influenced the practice of psychiatric therapy during the past 25 years: Minor tranquilizers, Antidepressants, and Neuroleptics. 1. From the clinical point of view the effects of tranquilizers are more unspecific as compared to those of neuroleptic and antidepressant drugs. Only with the latter two it is possible to treat manifestations of endogenous psychoses (schizophrenic and affective psychoses). The appraisal of both, the advantages (e.g. effectiveness on the symptomatology of acute psychotic manifestations or prophylactic effect in longtime application) and the risks (e.g. side-effects) have to be the basis of treatment of each single patient. 2. The recovery of biochemical mechanisms of neuroleptic and antidepressant drugs (especially of the effects on biogenic amines in CNS) is the most important advance in clearing up the biochemical disturbances in endogenous psychoses.", "contents": "[Psychotropic drugs--real progress or danger? (author's transl)]. Three types of modern psychotropic drugs strongly influenced the practice of psychiatric therapy during the past 25 years: Minor tranquilizers, Antidepressants, and Neuroleptics. 1. From the clinical point of view the effects of tranquilizers are more unspecific as compared to those of neuroleptic and antidepressant drugs. Only with the latter two it is possible to treat manifestations of endogenous psychoses (schizophrenic and affective psychoses). The appraisal of both, the advantages (e.g. effectiveness on the symptomatology of acute psychotic manifestations or prophylactic effect in longtime application) and the risks (e.g. side-effects) have to be the basis of treatment of each single patient. 2. The recovery of biochemical mechanisms of neuroleptic and antidepressant drugs (especially of the effects on biogenic amines in CNS) is the most important advance in clearing up the biochemical disturbances in endogenous psychoses."}
{"id": "PMID:22778", "title": "Effects of sodium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells.", "content": "Energized cells of Streptococcus lactis conserve and transduce energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). An increase in energy-consuming processes, such as cation transport, would be expected to result in a change in the steady state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltaph) from the distribution of a weak acid. In glycolyzing cells incubated at pH5 the addition of NaCl to 200 mM partially dissipated the deltap by decreasing deltapsi, while the delta pH was constant. The deltap was also determined independently from the accumulation levels of thiomethyl-beta-galactoside. The deltap values decreased in cells fermenting glucose at pH 5 or pH 7 when NaCl was added, while the deltapH values were unaffected; cells fermenting arginine at pH 7 showed similar effects. Thus, these nongrowing cells cannot fully compensate for the energy demand of cation transport.", "contents": "Effects of sodium ions on the electrical and pH gradients across the membrane of Streptococcus lactis cells. Energized cells of Streptococcus lactis conserve and transduce energy at the plasma membrane in the form of an electrochemical gradient of hydrogen ions (deltap). An increase in energy-consuming processes, such as cation transport, would be expected to result in a change in the steady state deltap. We determined the electrical gradient (deltapsi) from the fluorescence of a membrane potential-sensitive cyanine dye, and the chemical H+ gradient (deltaph) from the distribution of a weak acid. In glycolyzing cells incubated at pH5 the addition of NaCl to 200 mM partially dissipated the deltap by decreasing deltapsi, while the delta pH was constant. The deltap was also determined independently from the accumulation levels of thiomethyl-beta-galactoside. The deltap values decreased in cells fermenting glucose at pH 5 or pH 7 when NaCl was added, while the deltapH values were unaffected; cells fermenting arginine at pH 7 showed similar effects. Thus, these nongrowing cells cannot fully compensate for the energy demand of cation transport."}
{"id": "PMID:22779", "title": "Energetics of galactose, proline, and glutamine transport in a cytochrome-deficient mutant of Salmonella typhimurium.", "content": "The effect of inhibitors and uncouplers on the osmotic shock-sensitive transport systems for glutamine and galactose (by the beta-methyl galactoside permease) was compared to their effect on the osmotic shock-resistant proline and galactose permease systems in cytochrome-deficient cells of Salmonella typhimurium SASY28. Both osmotic shock-sensitive and -resistant systems were sensitive to uncouplers and to inhibitors of the membrane-bound Ca2+, Mg2+-activated adenosine triphosphatase. This suggests that uptake by both types of systems is energized in these cells by an electrochemical gradient of protons formed by ATP hydrolysis through the ATPase.", "contents": "Energetics of galactose, proline, and glutamine transport in a cytochrome-deficient mutant of Salmonella typhimurium. The effect of inhibitors and uncouplers on the osmotic shock-sensitive transport systems for glutamine and galactose (by the beta-methyl galactoside permease) was compared to their effect on the osmotic shock-resistant proline and galactose permease systems in cytochrome-deficient cells of Salmonella typhimurium SASY28. Both osmotic shock-sensitive and -resistant systems were sensitive to uncouplers and to inhibitors of the membrane-bound Ca2+, Mg2+-activated adenosine triphosphatase. This suggests that uptake by both types of systems is energized in these cells by an electrochemical gradient of protons formed by ATP hydrolysis through the ATPase."}
{"id": "PMID:22775", "title": "[Model of motion sickness in dogs for assessing the effectiveness of pharmacological substances].", "content": "The paper describes a model of motion sickness for dogs. The method is based on the simultaneous use of vertical and rotatory movement of the device with a continuously varying angular velocity of rotation to generate Coriolis acceleration. The exposure increases significantly the number of sick animals to be used in the selection of antimotion drugs. Diphenidol, marezine, tigane, bromotigane and metachloropromide were tested. Diphenidol and to a lesser extent marezine and metachloropromide proved effective. Tigane and bromotigane were ineffective against motion sickness.", "contents": "[Model of motion sickness in dogs for assessing the effectiveness of pharmacological substances]. The paper describes a model of motion sickness for dogs. The method is based on the simultaneous use of vertical and rotatory movement of the device with a continuously varying angular velocity of rotation to generate Coriolis acceleration. The exposure increases significantly the number of sick animals to be used in the selection of antimotion drugs. Diphenidol, marezine, tigane, bromotigane and metachloropromide were tested. Diphenidol and to a lesser extent marezine and metachloropromide proved effective. Tigane and bromotigane were ineffective against motion sickness."}
{"id": "PMID:22776", "title": "[Hygienic evaluation of the water reclaimed from various moisture-containing wastes].", "content": "The paper reviews 5 experiments on 25 healthy male test subjects, aged 20-36. For drinking and cooking they used water reclaimed from various water-containing wastes (atmospheric condensate, urine, fluids used in engineering processes and biological wastes) by the oxidation-catalytic and sorption techniques. The resultant water was saturated with salts and decontaminated by ionic silver at a dose of 0.1 mg/l. The experimental data on the excretion of water and minerals allow the conclusion that reclaimed and conditioned water is physiologically adequate and that the human body reacts to its intake as it does to normal potable water.", "contents": "[Hygienic evaluation of the water reclaimed from various moisture-containing wastes]. The paper reviews 5 experiments on 25 healthy male test subjects, aged 20-36. For drinking and cooking they used water reclaimed from various water-containing wastes (atmospheric condensate, urine, fluids used in engineering processes and biological wastes) by the oxidation-catalytic and sorption techniques. The resultant water was saturated with salts and decontaminated by ionic silver at a dose of 0.1 mg/l. The experimental data on the excretion of water and minerals allow the conclusion that reclaimed and conditioned water is physiologically adequate and that the human body reacts to its intake as it does to normal potable water."}
{"id": "PMID:22780", "title": "Pilot open-label study of triazolam in the treatment of insomnia following alcohol withdrawal.", "content": "Insomnia and anxiety decreased in 12 outpatients taking triazolam following alcohol withdrawal.", "contents": "Pilot open-label study of triazolam in the treatment of insomnia following alcohol withdrawal. Insomnia and anxiety decreased in 12 outpatients taking triazolam following alcohol withdrawal."}
{"id": "PMID:22777", "title": "[Variants of the control over a gas-exchange closed ecosystem with a periodically operating autotrophic component].", "content": "The paper discusses the problem of how to control a gas exchange closed ecosystem that consists of autotrophic and heterotrophic components and operates periodically in the light or in the dark. The purpose of the control is to maintain the steady state of an ecosystem with a man-oriented atmosphere. This problem of control has different solutions each of which is characterized by a set of six dimensionless variables associated with three equations--steady-state conditions. The physical characteristics of the variables and conditions of similarity of ecosystems are described. The resultant methods of control are evaluated from the point of view of economic operation of the ecosystem and the level of stability of its amosphere. The class of ecosystems for which the results obtained are valid in the event of accidental perturbations is presented.", "contents": "[Variants of the control over a gas-exchange closed ecosystem with a periodically operating autotrophic component]. The paper discusses the problem of how to control a gas exchange closed ecosystem that consists of autotrophic and heterotrophic components and operates periodically in the light or in the dark. The purpose of the control is to maintain the steady state of an ecosystem with a man-oriented atmosphere. This problem of control has different solutions each of which is characterized by a set of six dimensionless variables associated with three equations--steady-state conditions. The physical characteristics of the variables and conditions of similarity of ecosystems are described. The resultant methods of control are evaluated from the point of view of economic operation of the ecosystem and the level of stability of its amosphere. The class of ecosystems for which the results obtained are valid in the event of accidental perturbations is presented."}
{"id": "PMID:22783", "title": "[Diagnosis and treatment of postoperative infections following hip injuries].", "content": "The authors studied the diagnosis and treatment of posttraumatic infections of the hip joint, based on their own material. In case of latent infection the increased sedimentation rate and taking of comparative X-ray films are held important, that shows a narrowing and disappearance of the sclerosed edge of the acetabulum. Following dislocation of the hip joint ankylosis may be attained, but after fractures of the proximal and of the femur the infection cannot be cured, unless the nail and the head of the femur are removed.", "contents": "[Diagnosis and treatment of postoperative infections following hip injuries]. The authors studied the diagnosis and treatment of posttraumatic infections of the hip joint, based on their own material. In case of latent infection the increased sedimentation rate and taking of comparative X-ray films are held important, that shows a narrowing and disappearance of the sclerosed edge of the acetabulum. Following dislocation of the hip joint ankylosis may be attained, but after fractures of the proximal and of the femur the infection cannot be cured, unless the nail and the head of the femur are removed."}
{"id": "PMID:22785", "title": "[Treatment of childhood humeral fractures by wire fixation].", "content": "Out of 526 upper limb fractures treated in the Pediatric Surgery Department of the P\u00e9terfy S\u00e1ndor Hospital between 1970-1975, 63 patients were operated on. (11.9%). Fractures in childhood are generally treated by closed methods because healing of the growing bone is favourable. If it is reasonable, fractures of the forearm bones are successfully treated by means of intramedullary wire fixation, fractures of the elbow by means of transfixation. No septic complication occured following operation. Growth disturbancies were not observed in the affected bones after the operative intervention in the course of 1 to 5 years. On this ground the author recommends the adaptational \"minimal\" osteosynthesis in the treatment of fractures in infancy, if closed methods do not promise optimal results.", "contents": "[Treatment of childhood humeral fractures by wire fixation]. Out of 526 upper limb fractures treated in the Pediatric Surgery Department of the P\u00e9terfy S\u00e1ndor Hospital between 1970-1975, 63 patients were operated on. (11.9%). Fractures in childhood are generally treated by closed methods because healing of the growing bone is favourable. If it is reasonable, fractures of the forearm bones are successfully treated by means of intramedullary wire fixation, fractures of the elbow by means of transfixation. No septic complication occured following operation. Growth disturbancies were not observed in the affected bones after the operative intervention in the course of 1 to 5 years. On this ground the author recommends the adaptational \"minimal\" osteosynthesis in the treatment of fractures in infancy, if closed methods do not promise optimal results."}
{"id": "PMID:22787", "title": "[The role of orthopedic surgery in the treatment of spastic patients].", "content": "The authors performed 958 operations on spastic patients. Based on this clinical material, they introduce the possibilities and principles of operative treatment. Position of joints in the lower limb, their synergism and compensatory changes in a closed kinetic chain are analysed in the article. These factors must be attended to carefully if one should decide the site and variety of operation to be performed. The authors suggest that patients should be operated on early, in certain cases even preventive operation is necessary. Results are better if children who already can stand and walk are operated on, but in many cases operation itself is needed to enable them to these activities. Results were good in 83,2%, no changes in 3,4%, worse in 4,2 out of the 716 operations evaluated. Operative treatment along with conductive pedagogy and other methods of physiotherapy help these patients to be able to take care of themselves and to become useful members of society.", "contents": "[The role of orthopedic surgery in the treatment of spastic patients]. The authors performed 958 operations on spastic patients. Based on this clinical material, they introduce the possibilities and principles of operative treatment. Position of joints in the lower limb, their synergism and compensatory changes in a closed kinetic chain are analysed in the article. These factors must be attended to carefully if one should decide the site and variety of operation to be performed. The authors suggest that patients should be operated on early, in certain cases even preventive operation is necessary. Results are better if children who already can stand and walk are operated on, but in many cases operation itself is needed to enable them to these activities. Results were good in 83,2%, no changes in 3,4%, worse in 4,2 out of the 716 operations evaluated. Operative treatment along with conductive pedagogy and other methods of physiotherapy help these patients to be able to take care of themselves and to become useful members of society."}
{"id": "PMID:22788", "title": "[Possibilities of treatment of open fractures of the tibia].", "content": "Results of healing in 477 cases of open leg fractures treated in the Central Institut of Traumatology in Budapest are analysed in the article. 47,2% of cases were treated by closed methods. The authors are convinced that careful conservative management leads to good results, if the type of the fracture is suitable. Conditions of operative treatment are outlined. In favourable circumstances a stable internal fixation should be performed, otherwise inramedullary wiring and plaster may hold the fragments until healing occurs. Soft tissues should be handled carefully and placing sutures under tension must be avoided, by all means.", "contents": "[Possibilities of treatment of open fractures of the tibia]. Results of healing in 477 cases of open leg fractures treated in the Central Institut of Traumatology in Budapest are analysed in the article. 47,2% of cases were treated by closed methods. The authors are convinced that careful conservative management leads to good results, if the type of the fracture is suitable. Conditions of operative treatment are outlined. In favourable circumstances a stable internal fixation should be performed, otherwise inramedullary wiring and plaster may hold the fragments until healing occurs. Soft tissues should be handled carefully and placing sutures under tension must be avoided, by all means."}
{"id": "PMID:22789", "title": "[Stable osteosynthesis on the hand].", "content": "The authors write on the usefulness of the A.S.I.F. Small Fragment Instrumentary, its possible ways of application in the treatment of fractures of bones of the hand. The operative techniques is introduced, indication and contraindications based on the clinical material of the authors are discussed in the article. Limitations to the application of this method are also included.", "contents": "[Stable osteosynthesis on the hand]. The authors write on the usefulness of the A.S.I.F. Small Fragment Instrumentary, its possible ways of application in the treatment of fractures of bones of the hand. The operative techniques is introduced, indication and contraindications based on the clinical material of the authors are discussed in the article. Limitations to the application of this method are also included."}
{"id": "PMID:22790", "title": "[Syringomyelia with severe osteo-articular changes].", "content": "Attention was drawn to a patient after admission to the Central Institute of Oncology, and syringomyelia was diagnosed on the basis of X-ray films taken by the author. The deformations were symmetrical and they were localized in the area of innervation of the C VI, VII, D I segment. The radiological diagnosis was proved by the neurological examinations.", "contents": "[Syringomyelia with severe osteo-articular changes]. Attention was drawn to a patient after admission to the Central Institute of Oncology, and syringomyelia was diagnosed on the basis of X-ray films taken by the author. The deformations were symmetrical and they were localized in the area of innervation of the C VI, VII, D I segment. The radiological diagnosis was proved by the neurological examinations."}
{"id": "PMID:22792", "title": "Evidence for inhibition of dopamine-beta-hydroxylase in vivo after sub-acute pyrazole treatment in rats.", "content": "Pyrazole, a widely used inhibitor of alcohol dehydrogenase, has been shown to cause a decrease of brain and heart noradrenaline (NA). An attempt to explain the mechanism of this effect is now described. L-DOPA (50-200 mg/kg, s.c.) was unable to restore brain or heart noradrenaline levels in pyrazole pre-treated rats. After monoamine oxidase inhibition with tranylcypromine or pargyline there was a slight increase in brain NA in these rats but no further increase was observed in response to L-DOPA (30 mg/kg). Brain dopamine levels were relatively higher in pyrazole pre-treated rats. This difference was particularly clear in the hypothalamus but not present at all in striatum. It was impossible to duplicate the above results using nialamide as the monoamine oxidase inhibitor. After depletion of monoamine stores by reserpine (2 x 2 mg/kg) or oxypertine (75 mg/kg) and treatment with tranylcypromine and L-DOPA it is possible to get an indication of the maximal rate of synthesis of NA. In pyrazole treated rats synthesis of NA in brain was 70% reduced and about 50% reduced in heart. Synthesis of dopamine from L-DOPA was unimpaired. Dopamine-beta-hydroxylase activity in the hypothalamus of rats treated for four days with pyrazole (100 mg/kg i.p.) was more than 40% reduced. This inhibition could not be obtained by addition of pyrazole to samples of purified dopamine-beta-hydroxylase. The results strongly suggest that the reason for the decrease in brain and peripheral NA seen after pyrazole administration in rats is due to inhibition of dopamine-beta-hydroxylase.", "contents": "Evidence for inhibition of dopamine-beta-hydroxylase in vivo after sub-acute pyrazole treatment in rats. Pyrazole, a widely used inhibitor of alcohol dehydrogenase, has been shown to cause a decrease of brain and heart noradrenaline (NA). An attempt to explain the mechanism of this effect is now described. L-DOPA (50-200 mg/kg, s.c.) was unable to restore brain or heart noradrenaline levels in pyrazole pre-treated rats. After monoamine oxidase inhibition with tranylcypromine or pargyline there was a slight increase in brain NA in these rats but no further increase was observed in response to L-DOPA (30 mg/kg). Brain dopamine levels were relatively higher in pyrazole pre-treated rats. This difference was particularly clear in the hypothalamus but not present at all in striatum. It was impossible to duplicate the above results using nialamide as the monoamine oxidase inhibitor. After depletion of monoamine stores by reserpine (2 x 2 mg/kg) or oxypertine (75 mg/kg) and treatment with tranylcypromine and L-DOPA it is possible to get an indication of the maximal rate of synthesis of NA. In pyrazole treated rats synthesis of NA in brain was 70% reduced and about 50% reduced in heart. Synthesis of dopamine from L-DOPA was unimpaired. Dopamine-beta-hydroxylase activity in the hypothalamus of rats treated for four days with pyrazole (100 mg/kg i.p.) was more than 40% reduced. This inhibition could not be obtained by addition of pyrazole to samples of purified dopamine-beta-hydroxylase. The results strongly suggest that the reason for the decrease in brain and peripheral NA seen after pyrazole administration in rats is due to inhibition of dopamine-beta-hydroxylase."}
{"id": "PMID:22793", "title": "Physicians, physicians' assistants, and the social characteristics of patients in southern Appalachia.", "content": "A focus on health care delivery systems and the emergence of New Health Practitioners, particularly Physicians' Assistants (PAs), represents one of the more significant nonbiomedical developments in American medicine since World War II. Much discussion about PAs revolves around the kinds of illnesses they are qualified to treat which then permits physicians to concentrate on patients with other types of illnesses. Ignored in this focus on illness characteristics is the possibility that physicians and PAs may treat patients with different social characteristics. That issue is the topic of this paper. Differences between the status characteristics of physician and PA patients are reported for a rural community where PAs and physicians work side by side in the same offices. The relationships observed in this rural community suggest that the higher a patient's socioeconomic status, the more likely (s)he is to be treated by the physician.", "contents": "Physicians, physicians' assistants, and the social characteristics of patients in southern Appalachia. A focus on health care delivery systems and the emergence of New Health Practitioners, particularly Physicians' Assistants (PAs), represents one of the more significant nonbiomedical developments in American medicine since World War II. Much discussion about PAs revolves around the kinds of illnesses they are qualified to treat which then permits physicians to concentrate on patients with other types of illnesses. Ignored in this focus on illness characteristics is the possibility that physicians and PAs may treat patients with different social characteristics. That issue is the topic of this paper. Differences between the status characteristics of physician and PA patients are reported for a rural community where PAs and physicians work side by side in the same offices. The relationships observed in this rural community suggest that the higher a patient's socioeconomic status, the more likely (s)he is to be treated by the physician."}
{"id": "PMID:22794", "title": "The distribution of physician extenders.", "content": "As part of the Medicare Physician Extender Reimbursement Study, a mail survey was conducted of 5,572 physician extenders (PEs) to identify potential study participants. Analysis of survey results indicates that PEs are distributed disproportionately more often than physicians to primary care practices and to rural low income areas. However, there are substantial differences among types of PEs with regard to practice location and practice arrangement. The relationship between these findings and the distribution of other medical manpower and innovations is then discussed.", "contents": "The distribution of physician extenders. As part of the Medicare Physician Extender Reimbursement Study, a mail survey was conducted of 5,572 physician extenders (PEs) to identify potential study participants. Analysis of survey results indicates that PEs are distributed disproportionately more often than physicians to primary care practices and to rural low income areas. However, there are substantial differences among types of PEs with regard to practice location and practice arrangement. The relationship between these findings and the distribution of other medical manpower and innovations is then discussed."}
{"id": "PMID:22795", "title": "Physician assistants: an overview of an emerging health profession.", "content": "This article describes the background characteristics, work environments, and job characteristics of the physician assistant profession as they existed in late 1974 and early 1975. Of the 939 physician assistants participating in this study, three-fourths were working in primary care specialties and half were located in communities having fewer than 50,000 persons. Favorable levels of responsibility for patient care, supervisory support, and role acceptance were reported by respondents. The mean income was $14,285. Job opportunities appeared plentiful, but career opportunities were considered by most to be either limited or nonexistent. Physician assistants are providing important additional medical manpower in primary care fields and in smaller communities, but the preceived lack of opportunities for career advancement may prove to be a significant problem for this emerging health profession in the years ahead.", "contents": "Physician assistants: an overview of an emerging health profession. This article describes the background characteristics, work environments, and job characteristics of the physician assistant profession as they existed in late 1974 and early 1975. Of the 939 physician assistants participating in this study, three-fourths were working in primary care specialties and half were located in communities having fewer than 50,000 persons. Favorable levels of responsibility for patient care, supervisory support, and role acceptance were reported by respondents. The mean income was $14,285. Job opportunities appeared plentiful, but career opportunities were considered by most to be either limited or nonexistent. Physician assistants are providing important additional medical manpower in primary care fields and in smaller communities, but the preceived lack of opportunities for career advancement may prove to be a significant problem for this emerging health profession in the years ahead."}
{"id": "PMID:22796", "title": "The effectiveness and cost of acute respiratory illness medical care provided by physicians and algorithm-assisted physicians' assistants.", "content": "The medical management of patients with acute respiratory illnesses was analyzed at two different clinics during a 14- to 21-month period. Patients received care from either physicians or physician-supervised physician's assistants (PA). The PAs used respiratory illness clinical algorithms to guide their choice of diagnostic tests and treatment. Illness outcome, patient satisfaction, and medical care cost data were obtained for all patients approximately two weeks after the index illness. Despite significant differences in patient population characteristics, illness outcomes were similar, regardless of the provider's educational background. Medical care costs, however, were highest for the physician's patients. For all patients, diagnostic tests contributed about one-third of the total direct costs, mainly because of chest x-ray and throat culture use. Sixty to eighty per cent of medication costs were due to nonprescription drugs used principally for symptom relief. The data demonstrate that the medical care delivered by these physician's assistants was as effective and less costly than the care provided by physicians. Reducing chest x-ray and throat culture use would have a significant economic impact, without adversely affecting medical care effectiveness.", "contents": "The effectiveness and cost of acute respiratory illness medical care provided by physicians and algorithm-assisted physicians' assistants. The medical management of patients with acute respiratory illnesses was analyzed at two different clinics during a 14- to 21-month period. Patients received care from either physicians or physician-supervised physician's assistants (PA). The PAs used respiratory illness clinical algorithms to guide their choice of diagnostic tests and treatment. Illness outcome, patient satisfaction, and medical care cost data were obtained for all patients approximately two weeks after the index illness. Despite significant differences in patient population characteristics, illness outcomes were similar, regardless of the provider's educational background. Medical care costs, however, were highest for the physician's patients. For all patients, diagnostic tests contributed about one-third of the total direct costs, mainly because of chest x-ray and throat culture use. Sixty to eighty per cent of medication costs were due to nonprescription drugs used principally for symptom relief. The data demonstrate that the medical care delivered by these physician's assistants was as effective and less costly than the care provided by physicians. Reducing chest x-ray and throat culture use would have a significant economic impact, without adversely affecting medical care effectiveness."}
{"id": "PMID:22797", "title": "[Changes of serum and urinary uric-acid levels after portacaval anastomosis in the rat].", "content": "Significantly higher levels of uric acid in serum and urine together with increased urine volume and pH were observed in rats after portacaval end-to-side anastomosis in comparison to sham-operated and non-operated pair-fed controls. An increased supply of endogenous uric acid by reduced transformation of uric acid to allantoin and decreased uricase activity in the liver was assumed. Adaptation of enzyme activities of other metabolic pathways of the liver after PCA due to diminished blood and oxygen supply were described in previous experiments. This model seems suitable for other studies on hyperuricemia, hyperuricosuria and uric acid lithiasis.", "contents": "[Changes of serum and urinary uric-acid levels after portacaval anastomosis in the rat]. Significantly higher levels of uric acid in serum and urine together with increased urine volume and pH were observed in rats after portacaval end-to-side anastomosis in comparison to sham-operated and non-operated pair-fed controls. An increased supply of endogenous uric acid by reduced transformation of uric acid to allantoin and decreased uricase activity in the liver was assumed. Adaptation of enzyme activities of other metabolic pathways of the liver after PCA due to diminished blood and oxygen supply were described in previous experiments. This model seems suitable for other studies on hyperuricemia, hyperuricosuria and uric acid lithiasis."}
{"id": "PMID:22798", "title": "The dietary regulation of stearyl coenzyme A desaturase activity and membrane fluidity in the rat aorta.", "content": "Numerous studies have demonstrated that alterations in membrane composition or fluidity are often associated with alterations in the properties of membrane-bound enzymes. In order to obtain membranes of varying fluidity, rats were fed diets that were either fat-free or supplemented with 15% safflower oil, and two properties associated with aorta and liver microsomal membranes were selected for study: stearyl CoA desaturase activity, and fluidity as monitored by fatty acid composition and microviscosity (measured by fluorescence depolarization). If fluidity directly modulates desaturase activity, one would predict that a low fluidity would stimulate the desaturase activity. Ten times more desaturase activity is present in aorta microsomes from rats on a fat-free diet than in microsomes from rats on a safflower oil supplemented diet. However, on the fat-free diet, these aorta microsomes were more fluid than those of rats fed safflower oil supplemented diet. The fluidity of liver microsomal membranes was not altered in response to diet, despite significant changes in desaturase enzyme content. The contrasting evidence presented here suggests that no correlation exists between desaturase enzyme activity and membrane fluidity in the two tissues studies. We have demonstrated that the aorta has appreciable capacity to desaturate stearyl CoA and that dietary manipulation causes significant changes in aorta membrane fluidity that may be of sufficient magnitude to affect the overall metaboism of aorta cells.", "contents": "The dietary regulation of stearyl coenzyme A desaturase activity and membrane fluidity in the rat aorta. Numerous studies have demonstrated that alterations in membrane composition or fluidity are often associated with alterations in the properties of membrane-bound enzymes. In order to obtain membranes of varying fluidity, rats were fed diets that were either fat-free or supplemented with 15% safflower oil, and two properties associated with aorta and liver microsomal membranes were selected for study: stearyl CoA desaturase activity, and fluidity as monitored by fatty acid composition and microviscosity (measured by fluorescence depolarization). If fluidity directly modulates desaturase activity, one would predict that a low fluidity would stimulate the desaturase activity. Ten times more desaturase activity is present in aorta microsomes from rats on a fat-free diet than in microsomes from rats on a safflower oil supplemented diet. However, on the fat-free diet, these aorta microsomes were more fluid than those of rats fed safflower oil supplemented diet. The fluidity of liver microsomal membranes was not altered in response to diet, despite significant changes in desaturase enzyme content. The contrasting evidence presented here suggests that no correlation exists between desaturase enzyme activity and membrane fluidity in the two tissues studies. We have demonstrated that the aorta has appreciable capacity to desaturate stearyl CoA and that dietary manipulation causes significant changes in aorta membrane fluidity that may be of sufficient magnitude to affect the overall metaboism of aorta cells."}
{"id": "PMID:22803", "title": "Biochemical properties of a penicillinase from Escherichia coli carrying Rms 298.", "content": "We obtained two R plasmids, i.e., Rms195 and Rms298, from a clinical isolate, E. coli GN5503. Penicillin beta-lactamase (PCase) was extracted from ML1410 Rms195+ and Rms298+, and was purified by chromatography. Rms195 PCase was identical to the type I PCase mediated by R-TEM, RI and Rms212. The isoelectric point of Rms298 PCase was 5.9 and its molecular weight was 21,000 +/- 1,000. The substrate profile and physiochemical properties indicate that Rms298 PCase belongs to the type IV PCase mediated by Rms139 isolated from Pseudomonas aeruginosa.", "contents": "Biochemical properties of a penicillinase from Escherichia coli carrying Rms 298. We obtained two R plasmids, i.e., Rms195 and Rms298, from a clinical isolate, E. coli GN5503. Penicillin beta-lactamase (PCase) was extracted from ML1410 Rms195+ and Rms298+, and was purified by chromatography. Rms195 PCase was identical to the type I PCase mediated by R-TEM, RI and Rms212. The isoelectric point of Rms298 PCase was 5.9 and its molecular weight was 21,000 +/- 1,000. The substrate profile and physiochemical properties indicate that Rms298 PCase belongs to the type IV PCase mediated by Rms139 isolated from Pseudomonas aeruginosa."}
{"id": "PMID:22810", "title": "[Neurological complications following whooping-cough vaccination (author's transl)].", "content": "The clinical symptoms, frequency, etiology, pathogenesis and differential diagnosis of neurological complications following immunisation against pertussis are being discussed. Guide lines are presented for the evaluation of the causal connection between the observed complications and the vaccination.", "contents": "[Neurological complications following whooping-cough vaccination (author's transl)]. The clinical symptoms, frequency, etiology, pathogenesis and differential diagnosis of neurological complications following immunisation against pertussis are being discussed. Guide lines are presented for the evaluation of the causal connection between the observed complications and the vaccination."}
{"id": "PMID:22812", "title": "Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans.", "content": "Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.", "contents": "Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans. Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation."}
{"id": "PMID:22823", "title": "Differentiation of cardiac chronotropic and inotropic effects of beta-adrenoceptor agonists.", "content": "The relative inotropic and chronotropic activity of beta-adrenoceptor agonists was studied in the noradrenaline-depleted, anaesthetized cat. Terbutaline, a selective beta2-adrenoceptor agonist, gave at a certain dose a more pronounced chronotropic than inotropic response, while a new beta1-selective adrenoceptor agonist (-)-H 80/62 produced the same degree of chronotropic and inotropic stimulation. The results indicate that there is some difference between the beta-adrenoceptors in the sinus node mediating chronotropic stimulation and beta-adrenoceptors in the ventricular myocardium mediating stimulation of the contractile force. It has been shown that there are both beta1- and beta2-adrenoceptors in the heart (Carlsson et al., 1972). In the light of this finding it is hypothetized that there are differences in the relative distribution of beta1- and beta2-adrenoceptors in the sinus node and in the myocardium. Athough beta1 is the predominant type of beta-adrenoceptor in both regions, the beta1:beta2 concentration ratio seems to be higher in the myocardium, than in the sinus node.", "contents": "Differentiation of cardiac chronotropic and inotropic effects of beta-adrenoceptor agonists. The relative inotropic and chronotropic activity of beta-adrenoceptor agonists was studied in the noradrenaline-depleted, anaesthetized cat. Terbutaline, a selective beta2-adrenoceptor agonist, gave at a certain dose a more pronounced chronotropic than inotropic response, while a new beta1-selective adrenoceptor agonist (-)-H 80/62 produced the same degree of chronotropic and inotropic stimulation. The results indicate that there is some difference between the beta-adrenoceptors in the sinus node mediating chronotropic stimulation and beta-adrenoceptors in the ventricular myocardium mediating stimulation of the contractile force. It has been shown that there are both beta1- and beta2-adrenoceptors in the heart (Carlsson et al., 1972). In the light of this finding it is hypothetized that there are differences in the relative distribution of beta1- and beta2-adrenoceptors in the sinus node and in the myocardium. Athough beta1 is the predominant type of beta-adrenoceptor in both regions, the beta1:beta2 concentration ratio seems to be higher in the myocardium, than in the sinus node."}
{"id": "PMID:22824", "title": "Regulation of nerve growth factor content in C6 glioma cells by beta-adrenergic receptor stimulation.", "content": "The C6 glioma cell line contains nerve growth factor (NGF) which can be released into the medium. Treatment of the cells with beta-adrenoceptor agonists resulted in increased content of NGF in both the cells and the medium within a few hours, whereas alpha-adrenoceptor agonists were ineffective. The response was blocked by beta- but not alpha-adrenoceptor antagonists. The increase of the NGF content of glioma cells appeared to be mediated by an elevation of cyclic AMP or GMP. The addition to the cell cultures of other putative neurotransmitters failed to change the content of either NGF or cyclic AMP. These results are discussed with respect to a model for adrenergic neuron-glial interactions.", "contents": "Regulation of nerve growth factor content in C6 glioma cells by beta-adrenergic receptor stimulation. The C6 glioma cell line contains nerve growth factor (NGF) which can be released into the medium. Treatment of the cells with beta-adrenoceptor agonists resulted in increased content of NGF in both the cells and the medium within a few hours, whereas alpha-adrenoceptor agonists were ineffective. The response was blocked by beta- but not alpha-adrenoceptor antagonists. The increase of the NGF content of glioma cells appeared to be mediated by an elevation of cyclic AMP or GMP. The addition to the cell cultures of other putative neurotransmitters failed to change the content of either NGF or cyclic AMP. These results are discussed with respect to a model for adrenergic neuron-glial interactions."}
{"id": "PMID:22825", "title": "Effects of medium pH on p-aminohippurate transport in rat kidney fragments.", "content": "Addition of many oxidizable substrates to medium often enhances p-aminohippurate (PAH) transport by incubating renal tissue. Since the oxidation of various substrates by rat kidney tissue may change medium pH and this pH change has not been considered by many in conclusions, we followed the effects of medium pH on the magnitude and kinetics of in vitro PAH transport. Two previous studies employing rat kidney slices reported different optimal medium pH for PAH accumulation, i.e. pH 6.5 and pH 8.0. By repeating these studies over a wide range of medium pH, we confirmed the presence of enhanced steady state accumulation relative to pH 7.4 at two separate pH ranges, one at pH 6.7--6.9 (+ 15%), and the other at pH 7.7--7.9 (+ 22%). PAH influx, as measured by early tissue accumulation, was not different at pH 7.4 and 7.8; while at pH 6.8, it actually decreased. It was only later in the incubation that accumulation was greater at pH 6.8 and 7.8. Probably due to the small stimulation in steady state accumulation at either pH, we could not discern, by the methodology currently available, if this was secondary to augmented influx, decreased efflux, or a combination of both in the latter part of incubation. We conclude that the contribution secondary to medium pH changes must be considered when evaluating the effects of various substrates on PAH accumulation by kidney slices.", "contents": "Effects of medium pH on p-aminohippurate transport in rat kidney fragments. Addition of many oxidizable substrates to medium often enhances p-aminohippurate (PAH) transport by incubating renal tissue. Since the oxidation of various substrates by rat kidney tissue may change medium pH and this pH change has not been considered by many in conclusions, we followed the effects of medium pH on the magnitude and kinetics of in vitro PAH transport. Two previous studies employing rat kidney slices reported different optimal medium pH for PAH accumulation, i.e. pH 6.5 and pH 8.0. By repeating these studies over a wide range of medium pH, we confirmed the presence of enhanced steady state accumulation relative to pH 7.4 at two separate pH ranges, one at pH 6.7--6.9 (+ 15%), and the other at pH 7.7--7.9 (+ 22%). PAH influx, as measured by early tissue accumulation, was not different at pH 7.4 and 7.8; while at pH 6.8, it actually decreased. It was only later in the incubation that accumulation was greater at pH 6.8 and 7.8. Probably due to the small stimulation in steady state accumulation at either pH, we could not discern, by the methodology currently available, if this was secondary to augmented influx, decreased efflux, or a combination of both in the latter part of incubation. We conclude that the contribution secondary to medium pH changes must be considered when evaluating the effects of various substrates on PAH accumulation by kidney slices."}
{"id": "PMID:22826", "title": "Further evidence on the role of the hypothalamic afferents on the estrogen-induced prolactin release.", "content": "Serum prolactin (Prl) concentrations in ovariectomized rats were low without significant differences between morning and afternoon values. These levels were not affected by either frontal or caudal hypothalamic deafferentation. However, they increased after lesioning the hypothalamic median eminence (ME). Three days after the injection of 20 microgram estradiol benzoate (EB) into ovariectomized non-lesioned rats, a rise in serum Prl occurred in the afternoon but not in the morning. In animals with ME lesions estrogen enhanced both morning and afternoon values. The animals with caudal hypothalamic deafferentation and those which had undergone sham operation showed the same pattern as the normal animals. On the contrary, after estrogen treatment of rats with frontal hypothalamic deafferentation high serum Prl concentration during the morning and low levels in the afternoon were observed. It is concluded that estrogen effects on Prl secretion are in part mediated by frontal neural afferents to the hypothalamus. They would facilitate Prl inhibiting factor (PIF) secretion in the morning and inhibit PIF secretion in the afternoon.", "contents": "Further evidence on the role of the hypothalamic afferents on the estrogen-induced prolactin release. Serum prolactin (Prl) concentrations in ovariectomized rats were low without significant differences between morning and afternoon values. These levels were not affected by either frontal or caudal hypothalamic deafferentation. However, they increased after lesioning the hypothalamic median eminence (ME). Three days after the injection of 20 microgram estradiol benzoate (EB) into ovariectomized non-lesioned rats, a rise in serum Prl occurred in the afternoon but not in the morning. In animals with ME lesions estrogen enhanced both morning and afternoon values. The animals with caudal hypothalamic deafferentation and those which had undergone sham operation showed the same pattern as the normal animals. On the contrary, after estrogen treatment of rats with frontal hypothalamic deafferentation high serum Prl concentration during the morning and low levels in the afternoon were observed. It is concluded that estrogen effects on Prl secretion are in part mediated by frontal neural afferents to the hypothalamus. They would facilitate Prl inhibiting factor (PIF) secretion in the morning and inhibit PIF secretion in the afternoon."}
{"id": "PMID:22831", "title": "Thphenidate.", "content": "Plasma cyclic-AMP responses to adrenergic agonists are due to stimulation of the peripheral beta-adrenergic receptor. Mood responses to stimulants are thought to be due to actions leading to stimulation of central catecholamine receptors. To determine if a peripheral measure of receptor sensitivity could predict central mood effects of stimulants, the plasma cyclic-AMP response and the mood response to intravenous methylphenidate were determined simultaneously in 13 subjects. No correlation between the two responses was found.", "contents": "Thphenidate. Plasma cyclic-AMP responses to adrenergic agonists are due to stimulation of the peripheral beta-adrenergic receptor. Mood responses to stimulants are thought to be due to actions leading to stimulation of central catecholamine receptors. To determine if a peripheral measure of receptor sensitivity could predict central mood effects of stimulants, the plasma cyclic-AMP response and the mood response to intravenous methylphenidate were determined simultaneously in 13 subjects. No correlation between the two responses was found."}
{"id": "PMID:22836", "title": "Ultrasonographic study of the effect of different miotics on the eye components.", "content": "The effect of topical instillations of carbachol 3%, pilocarpine 2%, aceclidine 2%, aceclidine 2%-adrenaline 1%, and of the Ocusert delivery system was determined and compared in 151 eyes. The depth of the anterior chamber, the thickness and the position of the lens, the length of the vitreous and the refraction were studied. Aceclidine has negligible side effects on the ocular components (maximal change of the anterior chamber 0.20 mm; maximal change of the lens thickness 0.14 mm; maximal myopisation: -1.5 delta. Carbachol has the strongest side effects (maximal change of the anterior chamber 0.80 mm; maximal change of the lens thickness 0.80 mm; maximal myopisation -11.50 delta). Carbachol and pilocarpine may cause an important forward displacement of the lens with the risk of an angle-closure glaucoma in an eye with shallow anterior chamber.", "contents": "Ultrasonographic study of the effect of different miotics on the eye components. The effect of topical instillations of carbachol 3%, pilocarpine 2%, aceclidine 2%, aceclidine 2%-adrenaline 1%, and of the Ocusert delivery system was determined and compared in 151 eyes. The depth of the anterior chamber, the thickness and the position of the lens, the length of the vitreous and the refraction were studied. Aceclidine has negligible side effects on the ocular components (maximal change of the anterior chamber 0.20 mm; maximal change of the lens thickness 0.14 mm; maximal myopisation: -1.5 delta. Carbachol has the strongest side effects (maximal change of the anterior chamber 0.80 mm; maximal change of the lens thickness 0.80 mm; maximal myopisation -11.50 delta). Carbachol and pilocarpine may cause an important forward displacement of the lens with the risk of an angle-closure glaucoma in an eye with shallow anterior chamber."}
{"id": "PMID:22837", "title": "Phosphorylation of human erythrocyte membrane protein. Differences according to the assay procedure.", "content": "Phosphorylation of the human erythrocyte membrane proteins by gamma (32P) ATP was studied at pH 6 and pH 7.4, at 30 degrees C, with incubation times varying from 5 to 90 minutes, and with or without cyclic AMP. Incorporated radioactivity was much higher at pH 7.4 because of the prevalent activity of cAMP independent protein-kinase. Maximum incorporation was obtained in both pH after 30-45 minutes incubation, thereafter incorporated radioactivity was either stable or decreased. The part of the radioactivity due to cAMP stimulation was low and seems constant with the incubation time. Analysis of the substrates showed the predominant cAMP independent protein kinase activity in the phosphorylation of the spectrin second component and component III and that of cAMP dependent activity in the phosphorylation of component II4, IV5 and other minor bands.", "contents": "Phosphorylation of human erythrocyte membrane protein. Differences according to the assay procedure. Phosphorylation of the human erythrocyte membrane proteins by gamma (32P) ATP was studied at pH 6 and pH 7.4, at 30 degrees C, with incubation times varying from 5 to 90 minutes, and with or without cyclic AMP. Incorporated radioactivity was much higher at pH 7.4 because of the prevalent activity of cAMP independent protein-kinase. Maximum incorporation was obtained in both pH after 30-45 minutes incubation, thereafter incorporated radioactivity was either stable or decreased. The part of the radioactivity due to cAMP stimulation was low and seems constant with the incubation time. Analysis of the substrates showed the predominant cAMP independent protein kinase activity in the phosphorylation of the spectrin second component and component III and that of cAMP dependent activity in the phosphorylation of component II4, IV5 and other minor bands."}
{"id": "PMID:22838", "title": "Electrolyte pH changes in Human Milk.", "content": "Milk samples from 100 lactating mothers in the 10 days following delivery have been analyzed for pH, sodium, and potassium. The sodium concentration was high in the first 5 days, mean 21 +/- 5 mmol/liter, but fell to a mean 15 mmol/liter by the end of the first week and 12 mmol/liter by the 10th day. A similar downward trend was shown for potassium with an initial mean concentration of 18.5 mmol/liter falling to 15 mmol/liter by the 10th day. The pH fluctuated widely from day to day through a range of 6.75-7.42 with a mean pH 7.09. Considerable variations were shown in individuals from day to day, and from the beginning to the end of feeds (Table 1). The relatively high sodium concentration in the first few days may be an important defense mechanism against dehydration and hyponatremia during a period of relative thirst and starvation. The variation in the pH and electrolyte content of human milk may be expected to have some influence on the acid-base and electrolyte status of the infant.", "contents": "Electrolyte pH changes in Human Milk. Milk samples from 100 lactating mothers in the 10 days following delivery have been analyzed for pH, sodium, and potassium. The sodium concentration was high in the first 5 days, mean 21 +/- 5 mmol/liter, but fell to a mean 15 mmol/liter by the end of the first week and 12 mmol/liter by the 10th day. A similar downward trend was shown for potassium with an initial mean concentration of 18.5 mmol/liter falling to 15 mmol/liter by the 10th day. The pH fluctuated widely from day to day through a range of 6.75-7.42 with a mean pH 7.09. Considerable variations were shown in individuals from day to day, and from the beginning to the end of feeds (Table 1). The relatively high sodium concentration in the first few days may be an important defense mechanism against dehydration and hyponatremia during a period of relative thirst and starvation. The variation in the pH and electrolyte content of human milk may be expected to have some influence on the acid-base and electrolyte status of the infant."}
{"id": "PMID:22840", "title": "Effect of H+ on spontaneous neuronal activity in the surface layer of the rat medulla oblongata in vitro.", "content": "The effect of changing extracellular pH (pHe) on the spontaneous activity of neurons in brain slices taken from the ventral layer of the rat medulla oblongata was compared to the response of neurons in dorsal slices. In the ventral medulla, more than 50% of the neurons were excited by H+. These neurons were found just lateral to the pyramidal tract between the root of the hypoglossal nerve and the trapezoid body. In the dorsal medulla, low pHe caused an inhibition of activity in most neurons, although a few were excited. The fact that H+ elicted excitation predominantly in the ventral medullary substrate to respond to pHe changes. Depression of synaptic transmission within the neuronal network in the slice by reducing the [Ca2+]e and increasing the [Mg2+]e altered the nature of responses of neurons to H+: In the ventral medulla, the majority of neurons were inhibited by H+, whereas in the dorsal medulla more than 50% of neurons were excited. Therefore, \"specificity\" of the ventral medullary neurons seemed to be dependent upon intact synaptic connections. A possible role of acetylcholine-acetylcholinesterase system in the response of ventral medullary neurons to H+ is discussed.", "contents": "Effect of H+ on spontaneous neuronal activity in the surface layer of the rat medulla oblongata in vitro. The effect of changing extracellular pH (pHe) on the spontaneous activity of neurons in brain slices taken from the ventral layer of the rat medulla oblongata was compared to the response of neurons in dorsal slices. In the ventral medulla, more than 50% of the neurons were excited by H+. These neurons were found just lateral to the pyramidal tract between the root of the hypoglossal nerve and the trapezoid body. In the dorsal medulla, low pHe caused an inhibition of activity in most neurons, although a few were excited. The fact that H+ elicted excitation predominantly in the ventral medullary substrate to respond to pHe changes. Depression of synaptic transmission within the neuronal network in the slice by reducing the [Ca2+]e and increasing the [Mg2+]e altered the nature of responses of neurons to H+: In the ventral medulla, the majority of neurons were inhibited by H+, whereas in the dorsal medulla more than 50% of neurons were excited. Therefore, \"specificity\" of the ventral medullary neurons seemed to be dependent upon intact synaptic connections. A possible role of acetylcholine-acetylcholinesterase system in the response of ventral medullary neurons to H+ is discussed."}
{"id": "PMID:22841", "title": "The use of microelectrodes for measurement of local H+ activity in the cortical subarachnoidal space of cats.", "content": "pH microelectrodes with pointed tip (Hinke-type) were constructed for the continuous measurement of the local pH in the perivascular space of pial arteries in the feline cerebral cortex. The sensitive tip had a length of 20-60 mu and a base diameter of 10-25 mu. As reference electrode, a micropipette (tip diameter 2 mu), filled with 150 mM KCl was used. Calibration curves were linear and showed a sensitivity of 54.5-57.5 mV/pH unit at 38 degrees C. Advantages of such electrodes are the easy penetration of the subarachnoid membrane, the long life span, the quick response, and a minimal drift. The electrodes were tested in vivo during hyper- and hypoventilation and during local perivascular injection of mock spinal fluid at varying pH. A close correlation was observed between the change in perivascular pH and the corresponding change in pial arterial diameter.", "contents": "The use of microelectrodes for measurement of local H+ activity in the cortical subarachnoidal space of cats. pH microelectrodes with pointed tip (Hinke-type) were constructed for the continuous measurement of the local pH in the perivascular space of pial arteries in the feline cerebral cortex. The sensitive tip had a length of 20-60 mu and a base diameter of 10-25 mu. As reference electrode, a micropipette (tip diameter 2 mu), filled with 150 mM KCl was used. Calibration curves were linear and showed a sensitivity of 54.5-57.5 mV/pH unit at 38 degrees C. Advantages of such electrodes are the easy penetration of the subarachnoid membrane, the long life span, the quick response, and a minimal drift. The electrodes were tested in vivo during hyper- and hypoventilation and during local perivascular injection of mock spinal fluid at varying pH. A close correlation was observed between the change in perivascular pH and the corresponding change in pial arterial diameter."}
{"id": "PMID:22842", "title": "On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas.", "content": "DbcAMP greater than or equal to 0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-D-glucose and L-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neurotransmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative.", "contents": "On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas. DbcAMP greater than or equal to 0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-D-glucose and L-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neurotransmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative."}
{"id": "PMID:22843", "title": "The influence of the pH of feed on the acid-base balance of mink.", "content": "The acid-base balance in small carnivores (mink, Mustela vison) was examined during 6 feeding periods, when the same animals were given different feeds during a prolonged time. The feeds consisted of normal farm feed to which different amounts of sulphuric acid-preserved feed and feed silaged with organic acids were added (Tables I--II). When the pH of the feed was decreased to below 5.5, the acid-base balance of the animals was changed and metabolic acidosis occurred (Tables III--V, Fig. 1). On neutralization of the acid-preserved feed a normal acid-base balance could be maintained. However, the growth of the animals was reduced after prolonged feeding with silage as they lost weight during the following periods (Table vii).", "contents": "The influence of the pH of feed on the acid-base balance of mink. The acid-base balance in small carnivores (mink, Mustela vison) was examined during 6 feeding periods, when the same animals were given different feeds during a prolonged time. The feeds consisted of normal farm feed to which different amounts of sulphuric acid-preserved feed and feed silaged with organic acids were added (Tables I--II). When the pH of the feed was decreased to below 5.5, the acid-base balance of the animals was changed and metabolic acidosis occurred (Tables III--V, Fig. 1). On neutralization of the acid-preserved feed a normal acid-base balance could be maintained. However, the growth of the animals was reduced after prolonged feeding with silage as they lost weight during the following periods (Table vii)."}
{"id": "PMID:22844", "title": "[Piribedil, dopaminergic agonist. Prolonged clinical and electrophysiological study in 60 parkinsonian patients (author's transl)].", "content": "Sixty cases of Parkinson's disease were treated with piribedil alone (dose : 274 mg/day, duration : 20,4 months). The overall clinical improvement, confirmed by recordings of tremor and EMG, was 34%, tremor being improved of 59%. Before treatment, an intravenous test does of piribedil with recording made it possible to predict the effectiveness of oral treatment. Side-effects (vasomotor, digestive, psychiatric) were moderate. Orthostatic hypotension, dyskinesia and fluctuations were exceptional. The basic indication for piribedil lies in forms of recent onset in which tremor predominates, patients in whom L-dopa is contraindicated and a certain number in whom the latter has failed (tremor, fluctuating action).", "contents": "[Piribedil, dopaminergic agonist. Prolonged clinical and electrophysiological study in 60 parkinsonian patients (author's transl)]. Sixty cases of Parkinson's disease were treated with piribedil alone (dose : 274 mg/day, duration : 20,4 months). The overall clinical improvement, confirmed by recordings of tremor and EMG, was 34%, tremor being improved of 59%. Before treatment, an intravenous test does of piribedil with recording made it possible to predict the effectiveness of oral treatment. Side-effects (vasomotor, digestive, psychiatric) were moderate. Orthostatic hypotension, dyskinesia and fluctuations were exceptional. The basic indication for piribedil lies in forms of recent onset in which tremor predominates, patients in whom L-dopa is contraindicated and a certain number in whom the latter has failed (tremor, fluctuating action)."}
{"id": "PMID:22850", "title": "[Blood gas study in \"small airway disease\"].", "content": "A study of blood gasometry at rest and after exercise was carried out on 98 subjects: 49 healthy, 31 cases with \"small airway disease\" and 18 cases of clinically nondecompensated obstructive lung disease. The most interesting results arose from the study of PaO2. Its mean value increased after exercise in all groups, but in a manner less obvious as the bronchial obstruction appeared and increased. This increase was almost imperceptible in obstructive patients. The whole of gasometric behaviour ranged the subjects with \"small airway disease\" in an intermediate position between the normal controls and the obstructive patients. This finding leads the authors to suppose that the \"small airway disease\" implies the existence of disorders of intrapulmonary gas exchanges which foreshadow the obstructive disease.", "contents": "[Blood gas study in \"small airway disease\"]. A study of blood gasometry at rest and after exercise was carried out on 98 subjects: 49 healthy, 31 cases with \"small airway disease\" and 18 cases of clinically nondecompensated obstructive lung disease. The most interesting results arose from the study of PaO2. Its mean value increased after exercise in all groups, but in a manner less obvious as the bronchial obstruction appeared and increased. This increase was almost imperceptible in obstructive patients. The whole of gasometric behaviour ranged the subjects with \"small airway disease\" in an intermediate position between the normal controls and the obstructive patients. This finding leads the authors to suppose that the \"small airway disease\" implies the existence of disorders of intrapulmonary gas exchanges which foreshadow the obstructive disease."}
{"id": "PMID:22848", "title": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives: part IV. Mechanism and kinetics of specific acid-catalyzed hydrolysis of sulfadimidine.", "content": "The following products of acid hydrolysis of sulfadimidine (SDMP) were isolated and identified: sulfanilic acid (Sac), sulfanilamide (SA), 2-amino-4, 6-dimethylprimidine (ADMP) and 2-hydroxy-4, 6-dimethylpyrimidine (HDMP). The apparent first-order rate constants (k1, k2 and k3) were determined for the reaction: (formula: see text). The catalytic rate constants kH+ = ki/[H+] and the thermodynamic parameters delta Ha, delta H not equal to, deltaS not equal to, deltaG not equal to and log A were also determined for that reaction.", "contents": "Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives: part IV. Mechanism and kinetics of specific acid-catalyzed hydrolysis of sulfadimidine. The following products of acid hydrolysis of sulfadimidine (SDMP) were isolated and identified: sulfanilic acid (Sac), sulfanilamide (SA), 2-amino-4, 6-dimethylprimidine (ADMP) and 2-hydroxy-4, 6-dimethylpyrimidine (HDMP). The apparent first-order rate constants (k1, k2 and k3) were determined for the reaction: (formula: see text). The catalytic rate constants kH+ = ki/[H+] and the thermodynamic parameters delta Ha, delta H not equal to, deltaS not equal to, deltaG not equal to and log A were also determined for that reaction."}
{"id": "PMID:22847", "title": "The effects of lesion of mesolimbic dopamine neurons on pain threshold and morphine analgesia in rats.", "content": "Lesions of ventral tegmental area, localised in the region of A 10 group of dopaminergic mesolimbic neurons decreased the pain threshold in rats. The absolute threshold values in morphine treated animals with the above lesion were lower than in sham-operated controls, however, the thresholds expressed as percentage of predrug threshold values did not differ in both lesioned and sham-operated animals. It is thought, that lesions of ventral tegmental dopamine neurons decrease the pain threshold due to the increase of general excitability of animals, and that there is no direct involvement of the lesioned structure in the primary mechanism of morphine analgesia.", "contents": "The effects of lesion of mesolimbic dopamine neurons on pain threshold and morphine analgesia in rats. Lesions of ventral tegmental area, localised in the region of A 10 group of dopaminergic mesolimbic neurons decreased the pain threshold in rats. The absolute threshold values in morphine treated animals with the above lesion were lower than in sham-operated controls, however, the thresholds expressed as percentage of predrug threshold values did not differ in both lesioned and sham-operated animals. It is thought, that lesions of ventral tegmental dopamine neurons decrease the pain threshold due to the increase of general excitability of animals, and that there is no direct involvement of the lesioned structure in the primary mechanism of morphine analgesia."}
{"id": "PMID:22875", "title": "Interaction between phenylephrine hydrochloride and polyethylene glycol 400.", "content": "Evidence of complexing tendency of the water-soluble polymer polyethylene glycol 400 (PEG 400) and phenylephrine hydrochloride was supported by the equilibrium dialysis method. The influence of polymer concentration, ionic concentration, and hydrogen ion concentration of the systems on the interaction was investigated. Attempts to separate the complex by using paper chromatographic techniques have also been made.", "contents": "Interaction between phenylephrine hydrochloride and polyethylene glycol 400. Evidence of complexing tendency of the water-soluble polymer polyethylene glycol 400 (PEG 400) and phenylephrine hydrochloride was supported by the equilibrium dialysis method. The influence of polymer concentration, ionic concentration, and hydrogen ion concentration of the systems on the interaction was investigated. Attempts to separate the complex by using paper chromatographic techniques have also been made."}
{"id": "PMID:22880", "title": "Effect of anti-parkinsonism drugs on gastric emptying and intestinal transit in the rat.", "content": "The effect of atropine sulfate, trihexyphenidyl HCl, benztropine mesylate, diphenhydramine HCl and ethopropazine HCl on gastric emptying and intestinal transit of a phenol red solution in the rat was examined. Intraperitoneal administration of 0.3 mg/kg atropine, 1.2 mg/kg benztropine and trihexyphenidyl results in a marked decrease in gastric emptying and intestinal transit rate when compared to controls. Oral administration of these agents produced variable and unpredictable results. Single and multiple oral dose (0.6--3 mg/kg) studies with trihexyphenidyl failed to produce any significant decreases in gastric emptying rates. A single oral dose of benztropine (0.6--3 mg/kg) failed to reduce the gastric emptying rate, but multiple dose studies produced a significant decrease in the gastric emptying rate. Effects on gastric emptying and intestinal transit were seen after single and multiple oral doses of diphenhydramine and ethopropazine.", "contents": "Effect of anti-parkinsonism drugs on gastric emptying and intestinal transit in the rat. The effect of atropine sulfate, trihexyphenidyl HCl, benztropine mesylate, diphenhydramine HCl and ethopropazine HCl on gastric emptying and intestinal transit of a phenol red solution in the rat was examined. Intraperitoneal administration of 0.3 mg/kg atropine, 1.2 mg/kg benztropine and trihexyphenidyl results in a marked decrease in gastric emptying and intestinal transit rate when compared to controls. Oral administration of these agents produced variable and unpredictable results. Single and multiple oral dose (0.6--3 mg/kg) studies with trihexyphenidyl failed to produce any significant decreases in gastric emptying rates. A single oral dose of benztropine (0.6--3 mg/kg) failed to reduce the gastric emptying rate, but multiple dose studies produced a significant decrease in the gastric emptying rate. Effects on gastric emptying and intestinal transit were seen after single and multiple oral doses of diphenhydramine and ethopropazine."}
{"id": "PMID:22881", "title": "Cytological effects of phenothiazine tranquilizing agents on barley meristems.", "content": "A growth reduction of 30--40% was noted in barley plants grown in two phenothiazine tranquilizers. Similar reductions were noted in the number of mid-anaphase cells, indicating the reduced growth could have been the result of a reduced mitotic rate. Also observed were several types of chromosomal aberrations. Electron microscopy revealed less endoplasmic reticulum and cytoplasmic organelles in the treated cells than in untreated cells. Various sized discontinuities in the nuclear membrane was the most frequent abnormality observed in the electron micrographs. The abnormal nuclear membrane was possibly a result of enzyme degradation.", "contents": "Cytological effects of phenothiazine tranquilizing agents on barley meristems. A growth reduction of 30--40% was noted in barley plants grown in two phenothiazine tranquilizers. Similar reductions were noted in the number of mid-anaphase cells, indicating the reduced growth could have been the result of a reduced mitotic rate. Also observed were several types of chromosomal aberrations. Electron microscopy revealed less endoplasmic reticulum and cytoplasmic organelles in the treated cells than in untreated cells. Various sized discontinuities in the nuclear membrane was the most frequent abnormality observed in the electron micrographs. The abnormal nuclear membrane was possibly a result of enzyme degradation."}
{"id": "PMID:22886", "title": "[Pharmacologic effect of protracted neuroleptics, fluphenazine oenanthate and oxyprothepine oenanthate (VUFB 9447)].", "content": "Two neuroleptica with protracted effect, i.e. Fluphenazin-Oenanthat and Oxyprothepin-Oenanthat, were tested on rats, dogs and rabbits. It was found that both drugs, after intramuscular injection in doses between 5--30 mg/kg, produced a long-lasting neuroleptic effect, in particular the inhibition of conditioned reflexes in rats, the antagonistic effect against apomorphine vomiting in dogs and the EEG-brain activity specific for neuroleptica. Hardly any differences were found between the effects of the two drugs. Both neuroleptica caused interesting spike activity in the EEG-registration particularly in the limbic structures which have hitherto not been described in the literature.", "contents": "[Pharmacologic effect of protracted neuroleptics, fluphenazine oenanthate and oxyprothepine oenanthate (VUFB 9447)]. Two neuroleptica with protracted effect, i.e. Fluphenazin-Oenanthat and Oxyprothepin-Oenanthat, were tested on rats, dogs and rabbits. It was found that both drugs, after intramuscular injection in doses between 5--30 mg/kg, produced a long-lasting neuroleptic effect, in particular the inhibition of conditioned reflexes in rats, the antagonistic effect against apomorphine vomiting in dogs and the EEG-brain activity specific for neuroleptica. Hardly any differences were found between the effects of the two drugs. Both neuroleptica caused interesting spike activity in the EEG-registration particularly in the limbic structures which have hitherto not been described in the literature."}
{"id": "PMID:22889", "title": "[Tests on the vegetative dynamics of depression under thymoleptic treatment].", "content": "40 patients with endogenic depression, who exhibited an inhibited-mel ancholic symptomatology received Dibenzepin (30 patients) and Imipramin (10 patients) as a mood-elucidating and activating anti-depressant. Exact determinations of blood pressure, pulse rate, the orthostatic-reaction, Schellong's test and the cold-pressure test were carried out on these patients. The results were tabulated. They show fundamentally that (1) the thymoleptic circulatory reaction as a sign of the influence of the vegetative functions makes possible in many cases a prognosis of the secondary effects of treatment and (2) a strong acceleration in the rate of pulse, and a rise in the systolic blood pressure at rest as well as the normalization of the orthostatic-test chiefly indicate an improvement or remission of depression.", "contents": "[Tests on the vegetative dynamics of depression under thymoleptic treatment]. 40 patients with endogenic depression, who exhibited an inhibited-mel ancholic symptomatology received Dibenzepin (30 patients) and Imipramin (10 patients) as a mood-elucidating and activating anti-depressant. Exact determinations of blood pressure, pulse rate, the orthostatic-reaction, Schellong's test and the cold-pressure test were carried out on these patients. The results were tabulated. They show fundamentally that (1) the thymoleptic circulatory reaction as a sign of the influence of the vegetative functions makes possible in many cases a prognosis of the secondary effects of treatment and (2) a strong acceleration in the rate of pulse, and a rise in the systolic blood pressure at rest as well as the normalization of the orthostatic-test chiefly indicate an improvement or remission of depression."}
{"id": "PMID:22890", "title": "Does dopamine play a role in schizophrenia?", "content": "Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets of these drugs for the mental and the extrapyramidal actions respectively. Dopaminergic hyperfunction, induced by amphetamines or dopa, may lead to a disturbance mimicking paranoid schizophrenia, lending further support for a key role of dopamine in mental functions. While a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, aminoacid or peptide transmitters in schizophrenia cannot be disregarded.", "contents": "Does dopamine play a role in schizophrenia? Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets of these drugs for the mental and the extrapyramidal actions respectively. Dopaminergic hyperfunction, induced by amphetamines or dopa, may lead to a disturbance mimicking paranoid schizophrenia, lending further support for a key role of dopamine in mental functions. While a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, aminoacid or peptide transmitters in schizophrenia cannot be disregarded."}
{"id": "PMID:22891", "title": "[Behavior of some liver enzyme activities in newborn infants with jaundice treated with phototherapy].", "content": "The recent hypothesis that phototherapy is capable of altering the liver cell, enough to allow passive diffusion of free bilirubin from the blood to the bile, and the discovery of substantial differences between the breakdown products of bilirubin obtained in vivo and in vitro, has prompted the AA. to investigate the enzymatic values in newborn infants with jaundice undergoing phototherapy. A study was made of the variations of cytolithic enzymes (GPT-GOT-GLDH-SDH) and secretions enzymes (FA-LAP-gammaGT-CHE) before and after phototherapy among different sized groups of infants with jaundice, between the 36th and 40th week of the gestational age, and with body weight varying from 1940 to 4150 g. No significant alteration of the cytolithic enzymes were recorded and among the secretion enzymes only the gammaGT was seen to increase. According to the AA., phototherapy does not alter the presence of a possible transitory cholestasis in newborn infants with physiological jaundice and causes no significant damage to the liver cells.", "contents": "[Behavior of some liver enzyme activities in newborn infants with jaundice treated with phototherapy]. The recent hypothesis that phototherapy is capable of altering the liver cell, enough to allow passive diffusion of free bilirubin from the blood to the bile, and the discovery of substantial differences between the breakdown products of bilirubin obtained in vivo and in vitro, has prompted the AA. to investigate the enzymatic values in newborn infants with jaundice undergoing phototherapy. A study was made of the variations of cytolithic enzymes (GPT-GOT-GLDH-SDH) and secretions enzymes (FA-LAP-gammaGT-CHE) before and after phototherapy among different sized groups of infants with jaundice, between the 36th and 40th week of the gestational age, and with body weight varying from 1940 to 4150 g. No significant alteration of the cytolithic enzymes were recorded and among the secretion enzymes only the gammaGT was seen to increase. According to the AA., phototherapy does not alter the presence of a possible transitory cholestasis in newborn infants with physiological jaundice and causes no significant damage to the liver cells."}
{"id": "PMID:22894", "title": "Slow-drip dibenzepine infusion in depression. Proof of rapid efficacy by quantitative EEG and affect-polarity profile studies.", "content": "The efficacy of a new intensive antidepressive treatment procedure--48 h slow drip infusion with 1,440 mg dibenzepine2 and subsequent oral treatment--was investigated in endomorphous (endogenous) depressed patients. In addition to evaluations of alterations in psychopathology by clinicians, time of onset and the extent of the therapeutic effect was determined by the patients themselves using the affect-polarity profile, and by EEG power-spectral density analysis. Clinical improvement started as early as in the 3rd hour of the dibenzepine infusion and was predominantly due to an anxiolytic/sedative drug effect. The thymoleptic effect started at the end of the infusion and increased with progressing oral treatment up to the 3rd week. Neurophysiological changes were ahead of the psychopathological ones, since a statistical decrease in dominant frequency of the EEG occurred 1 h after the start of dibenzepine infusion.", "contents": "Slow-drip dibenzepine infusion in depression. Proof of rapid efficacy by quantitative EEG and affect-polarity profile studies. The efficacy of a new intensive antidepressive treatment procedure--48 h slow drip infusion with 1,440 mg dibenzepine2 and subsequent oral treatment--was investigated in endomorphous (endogenous) depressed patients. In addition to evaluations of alterations in psychopathology by clinicians, time of onset and the extent of the therapeutic effect was determined by the patients themselves using the affect-polarity profile, and by EEG power-spectral density analysis. Clinical improvement started as early as in the 3rd hour of the dibenzepine infusion and was predominantly due to an anxiolytic/sedative drug effect. The thymoleptic effect started at the end of the infusion and increased with progressing oral treatment up to the 3rd week. Neurophysiological changes were ahead of the psychopathological ones, since a statistical decrease in dominant frequency of the EEG occurred 1 h after the start of dibenzepine infusion."}
{"id": "PMID:22895", "title": "Separation and characterization of peptides of delta chain from haemoglobin A2 by fingerprint at pH 3.5.", "content": "Peptide mapping or fingerprint of delta chain of haemoglobin A2 at pH 3.5 in comparison at pH 6.4 was investigated. The peptides which are in the neutral zone at pH 6.4 can be separated with efficiency at pH 3.5 and this method makes the interpretation and extraction of several peptides easy.", "contents": "Separation and characterization of peptides of delta chain from haemoglobin A2 by fingerprint at pH 3.5. Peptide mapping or fingerprint of delta chain of haemoglobin A2 at pH 3.5 in comparison at pH 6.4 was investigated. The peptides which are in the neutral zone at pH 6.4 can be separated with efficiency at pH 3.5 and this method makes the interpretation and extraction of several peptides easy."}
{"id": "PMID:22900", "title": "Calcium transport and release by the sarcoplasmic reticulum.", "content": "The slow rate of calcium transport by cardiac sarcoplasmic reticulum vesicles, compared to those prepared from skeletal muscle, is due mainly to a lesser density of transport sites and a lower Ca2+ affinity. Because the turnover rate of the cardiac sarcoplasmic reticulum calcium pump is similar to that of comparable skeletal muscle preparations, the cardiac sarcoplasmic reticulum seems able to effect the slower relaxation of the heart. Calcium permeability of skeletal sarcoplasmic reticulum vesicles is increased when the Ca2+ concentration outside the vesicles is increased, or when that inside the vesicle is decreased.", "contents": "Calcium transport and release by the sarcoplasmic reticulum. The slow rate of calcium transport by cardiac sarcoplasmic reticulum vesicles, compared to those prepared from skeletal muscle, is due mainly to a lesser density of transport sites and a lower Ca2+ affinity. Because the turnover rate of the cardiac sarcoplasmic reticulum calcium pump is similar to that of comparable skeletal muscle preparations, the cardiac sarcoplasmic reticulum seems able to effect the slower relaxation of the heart. Calcium permeability of skeletal sarcoplasmic reticulum vesicles is increased when the Ca2+ concentration outside the vesicles is increased, or when that inside the vesicle is decreased."}
{"id": "PMID:22901", "title": "Isolation and enzymatic characterization of guinea pig cardiac sarcolemma.", "content": "Sarcolemma was isolated by fractionation of salt-extracted particles on two consecutive sucrose density gradients. Salt extraction of homogenates, rather than of washed particles, was found to preserve the activities of adenylate cyclase and ouabain-sensitive (Na+,-K+)-ATPase in the isolated sarcolemmal membranes. Purified sarcolemma contained substantial adenylate cyclase and guanylate cyclase activities that were stimulable by beta-adrenergic and muscarinic agonists, respectively. Significant ouabain-sensitive (Na+, K+)-ATPase activity as well as putative digitalis receptor activity was also present in sarcolemma. Cyclic nucleotide phosphodiesterases of sarcolemma, both cAMP- and cGMP-dependent, displayed positive cooperativity of substrate interactions; Ca2+ ions were found to increase the activity of the GMP-dependent enzyme.", "contents": "Isolation and enzymatic characterization of guinea pig cardiac sarcolemma. Sarcolemma was isolated by fractionation of salt-extracted particles on two consecutive sucrose density gradients. Salt extraction of homogenates, rather than of washed particles, was found to preserve the activities of adenylate cyclase and ouabain-sensitive (Na+,-K+)-ATPase in the isolated sarcolemmal membranes. Purified sarcolemma contained substantial adenylate cyclase and guanylate cyclase activities that were stimulable by beta-adrenergic and muscarinic agonists, respectively. Significant ouabain-sensitive (Na+, K+)-ATPase activity as well as putative digitalis receptor activity was also present in sarcolemma. Cyclic nucleotide phosphodiesterases of sarcolemma, both cAMP- and cGMP-dependent, displayed positive cooperativity of substrate interactions; Ca2+ ions were found to increase the activity of the GMP-dependent enzyme."}
{"id": "PMID:22902", "title": "Properties of membrane-bound and soluble guanylate cyclase of cardiac and skeletal muscle.", "content": "Kinetic properties of guanylate cyclase present in the washed particles, plasma membranes, and the soluble cytoplasm of heart and skeletal muscle are described; properties of the enzyme solubilized by Triton X-100 treatment of the particles or membrane fractions are also reported. It is apparent from the data that the membrane-bound guanylate cyclase in the cell may be regulated by acetylcholine, may exist as a metallo-protein with bound Mn2+ (essential for activity), and that Mg2+ regulates, whereas Ca2+ and nucleotides (especially ATP) modulate, guanylate cyclase activity. The findings also suggest that guanylate cyclase, similar to adenylate cyclase and (Na+, K+)-ATPase, is mainly located in the plasma membranes of heart and skeletal muscle.", "contents": "Properties of membrane-bound and soluble guanylate cyclase of cardiac and skeletal muscle. Kinetic properties of guanylate cyclase present in the washed particles, plasma membranes, and the soluble cytoplasm of heart and skeletal muscle are described; properties of the enzyme solubilized by Triton X-100 treatment of the particles or membrane fractions are also reported. It is apparent from the data that the membrane-bound guanylate cyclase in the cell may be regulated by acetylcholine, may exist as a metallo-protein with bound Mn2+ (essential for activity), and that Mg2+ regulates, whereas Ca2+ and nucleotides (especially ATP) modulate, guanylate cyclase activity. The findings also suggest that guanylate cyclase, similar to adenylate cyclase and (Na+, K+)-ATPase, is mainly located in the plasma membranes of heart and skeletal muscle."}
{"id": "PMID:22903", "title": "Metabolic effect of pH on myocardium of heart-lung preparation.", "content": "Cardiac performance and metabolism of heart-lung preparation of rat were studied with acid, normal, and alkali perfusions. Cardiac output, glucose uptake, and myocardial content of lactate, malate, glycerophosphate, and CP were increased in alkali and decreased in acid perfusion of 20 min. On the other hand, when pH of the perfusate was abruptly changed, CP and ATP were decreased independent of the performance. FDP was high and PEP was low in acute acidifying experiments. From these findings it is concluded that cardiac performance and carbohydrate metabolism are accelerated in alkali and depressed in acid perfusion, and that myocardial metabolism could be affected by pH not only secondary to the change of performance but also by itself.", "contents": "Metabolic effect of pH on myocardium of heart-lung preparation. Cardiac performance and metabolism of heart-lung preparation of rat were studied with acid, normal, and alkali perfusions. Cardiac output, glucose uptake, and myocardial content of lactate, malate, glycerophosphate, and CP were increased in alkali and decreased in acid perfusion of 20 min. On the other hand, when pH of the perfusate was abruptly changed, CP and ATP were decreased independent of the performance. FDP was high and PEP was low in acute acidifying experiments. From these findings it is concluded that cardiac performance and carbohydrate metabolism are accelerated in alkali and depressed in acid perfusion, and that myocardial metabolism could be affected by pH not only secondary to the change of performance but also by itself."}
{"id": "PMID:22904", "title": "Dose-dependent depression of cardiac function and metabolism by inhalation anesthetics in chronically instrumented dogs.", "content": "Halothane, methoxyflurane, and enflurane produce dose-dependent depression in ventricular function in the dog. Myocardial blood flow and oxygen consumption are decreased accordingly without evidence of myocardial tissue hypoxia. Low-dose fluoxene does not depress the heart, while there is less depression with high-dose fluroxene than with the other anesthetics. In spite of this depression, myocardial blood flow was unchanged, and the decreased oxygen consumption during high-dose fluroxene was a result of decreased oxygen extraction by the heart. Sympathetic nervous system stimulation produced by fluroxene anesthesia is probably responsible for these effects, but further work is necessary for confirmation of this hypothesis.", "contents": "Dose-dependent depression of cardiac function and metabolism by inhalation anesthetics in chronically instrumented dogs. Halothane, methoxyflurane, and enflurane produce dose-dependent depression in ventricular function in the dog. Myocardial blood flow and oxygen consumption are decreased accordingly without evidence of myocardial tissue hypoxia. Low-dose fluoxene does not depress the heart, while there is less depression with high-dose fluroxene than with the other anesthetics. In spite of this depression, myocardial blood flow was unchanged, and the decreased oxygen consumption during high-dose fluroxene was a result of decreased oxygen extraction by the heart. Sympathetic nervous system stimulation produced by fluroxene anesthesia is probably responsible for these effects, but further work is necessary for confirmation of this hypothesis."}
{"id": "PMID:22905", "title": "Control of energy production in cardiac muscle: effects of ischemia in acidosis.", "content": "Evidence is summarized indicating that mitochondrial respiration and citric acid cycle activity in the intact heart are controlled by the cytosolic phosphate potential and mitochondrial NAD oxidation-reduction state. Data are presented showing that the effect of respiratory acidosis is greater than that of metabolic acidosis in inhibiting left ventricular pressure development in the perfused rat heart, because of a greater fall of intracellular pH under the former conditions. Respiratory acidosis is shown to be readily associated with tissue hypoxia as a result of an increased vascular resistance and diminished flow rate through the coronary circulation. In nonischemic respiratory acidosis, the rate of ATP production is well balanced by the rate of ATP utilization, and tissue ATP and creatine-P levels remain approximately normal. Partially ischemic respiratory acidosis was associated with low tissue levels of ATP and creatine-P and high tissue levels of lactate and NADH. Ischemic areas with sharp border zones were visualized during and after an abrupt decrease of perfusion fluid pH by directly photographing NADH fluorescence from the surface of perfused hearts. Reversal of the hypodynamic state with partially ischemic respiratory acidosis could not be achieved by augmenting the coronary flow by means of an external pump. The demonstration of the existence of sharp zones of high pyridine nucleotide fluorescence adjacent to normal zones indicates a great heterogeneity of coronary perfusion and the existence of steep oxygen gradients in the intact heart.", "contents": "Control of energy production in cardiac muscle: effects of ischemia in acidosis. Evidence is summarized indicating that mitochondrial respiration and citric acid cycle activity in the intact heart are controlled by the cytosolic phosphate potential and mitochondrial NAD oxidation-reduction state. Data are presented showing that the effect of respiratory acidosis is greater than that of metabolic acidosis in inhibiting left ventricular pressure development in the perfused rat heart, because of a greater fall of intracellular pH under the former conditions. Respiratory acidosis is shown to be readily associated with tissue hypoxia as a result of an increased vascular resistance and diminished flow rate through the coronary circulation. In nonischemic respiratory acidosis, the rate of ATP production is well balanced by the rate of ATP utilization, and tissue ATP and creatine-P levels remain approximately normal. Partially ischemic respiratory acidosis was associated with low tissue levels of ATP and creatine-P and high tissue levels of lactate and NADH. Ischemic areas with sharp border zones were visualized during and after an abrupt decrease of perfusion fluid pH by directly photographing NADH fluorescence from the surface of perfused hearts. Reversal of the hypodynamic state with partially ischemic respiratory acidosis could not be achieved by augmenting the coronary flow by means of an external pump. The demonstration of the existence of sharp zones of high pyridine nucleotide fluorescence adjacent to normal zones indicates a great heterogeneity of coronary perfusion and the existence of steep oxygen gradients in the intact heart."}
{"id": "PMID:22906", "title": "Calcium ion in cardiac contractility.", "content": "Under physiological conditions where the intracellular Ca ion concentration does not exceed 3 X 10(-6) M, the sarcoplasmic reticulum plays a major role in the relaxation process of cardiac muscle; mitochondria do not take up a significant amount of Ca ion during this process. If cardiac muscle undergoes maximum contraction, in which the intracellular Ca ion concentration should reach 10(-4) M, the role of mitochondria in reducing intracellular Ca ion becomes appreciable. The relationship of the tension developed by cardiac glycerinated muscle fibers to the Ca ion concentration resembles the relationship of the amount of bound Ca of cardiac troponin to the Ca ion concentrations, being less steep in its slope compared with those of fast and slow skeletal muscles. This gentle slope seems to reflect the great diversity of affinities for Ca ion of the two Ca-binding sites of cardiac troponin, one being about 100 times that of the other.", "contents": "Calcium ion in cardiac contractility. Under physiological conditions where the intracellular Ca ion concentration does not exceed 3 X 10(-6) M, the sarcoplasmic reticulum plays a major role in the relaxation process of cardiac muscle; mitochondria do not take up a significant amount of Ca ion during this process. If cardiac muscle undergoes maximum contraction, in which the intracellular Ca ion concentration should reach 10(-4) M, the role of mitochondria in reducing intracellular Ca ion becomes appreciable. The relationship of the tension developed by cardiac glycerinated muscle fibers to the Ca ion concentration resembles the relationship of the amount of bound Ca of cardiac troponin to the Ca ion concentrations, being less steep in its slope compared with those of fast and slow skeletal muscles. This gentle slope seems to reflect the great diversity of affinities for Ca ion of the two Ca-binding sites of cardiac troponin, one being about 100 times that of the other."}
{"id": "PMID:22907", "title": "Myocardial metabolism during prolonged selectived hypothermic coronary perfusion.", "content": "In the study discussed below, we assessed the myocardial protection provided by our method of selective hypothermic coronary perfusion. Using arterial and coronary venous blood samples, the following biochemical aspects of myocardial metabolism were calculated: 1) coronary arteriovenous (A-V) pH difference, 2) O2 difference, 3) CO2 difference, 4) respiratory quotient, 5) coronary A-V pyruvate difference, 6) lactate difference, 7) cardiac excess lactate, and 8) redox potential difference. Results indicate that, during coronary perfusion performed according to out method, metabolic changes are minimal and easily reversible shortly after coronary perfusion is terminated.", "contents": "Myocardial metabolism during prolonged selectived hypothermic coronary perfusion. In the study discussed below, we assessed the myocardial protection provided by our method of selective hypothermic coronary perfusion. Using arterial and coronary venous blood samples, the following biochemical aspects of myocardial metabolism were calculated: 1) coronary arteriovenous (A-V) pH difference, 2) O2 difference, 3) CO2 difference, 4) respiratory quotient, 5) coronary A-V pyruvate difference, 6) lactate difference, 7) cardiac excess lactate, and 8) redox potential difference. Results indicate that, during coronary perfusion performed according to out method, metabolic changes are minimal and easily reversible shortly after coronary perfusion is terminated."}
{"id": "PMID:22924", "title": "Enamel microhardness and fluoride uptake underneath fermenting and non-fermenting artificial plaque.", "content": "Washed cells of Streptococcus sanguis were used to form artificial plaque on the surface of bovine enamel and incubated underneath buffer solutions, initial pH 6, for 36 h at 37 degrees C. The decrease in the microhardness of the enamel surface under fermenting \"plaque\" could be prevented with fluoride. Enamel under a fermenting \"plaque\" took up significantly more (P less than 0.0u) fluoride than enamel under a non-fermenting \"plaque\" (initial F- in buffer: 10 parts/10(6)). The artificial plaque did not accumulate fluoride. Within fermenting \"plaques/, the pH decreased significantly more without flouride (P less than 0.01) than with fluoride. Fluoride combined with sucrose more than negated the softening of the enamel caused by sucrose fermentation, i.e. it increased the hardness above the original values. The diffusion of fluoride through the fermenting artificial plaque was more rapid than through a non-fermenting plaque. These findings suggest that caries-conducive circumstances may promote fluoride uptake by enamel compared with non-caries-conducive circumstances.", "contents": "Enamel microhardness and fluoride uptake underneath fermenting and non-fermenting artificial plaque. Washed cells of Streptococcus sanguis were used to form artificial plaque on the surface of bovine enamel and incubated underneath buffer solutions, initial pH 6, for 36 h at 37 degrees C. The decrease in the microhardness of the enamel surface under fermenting \"plaque\" could be prevented with fluoride. Enamel under a fermenting \"plaque\" took up significantly more (P less than 0.0u) fluoride than enamel under a non-fermenting \"plaque\" (initial F- in buffer: 10 parts/10(6)). The artificial plaque did not accumulate fluoride. Within fermenting \"plaques/, the pH decreased significantly more without flouride (P less than 0.01) than with fluoride. Fluoride combined with sucrose more than negated the softening of the enamel caused by sucrose fermentation, i.e. it increased the hardness above the original values. The diffusion of fluoride through the fermenting artificial plaque was more rapid than through a non-fermenting plaque. These findings suggest that caries-conducive circumstances may promote fluoride uptake by enamel compared with non-caries-conducive circumstances."}
{"id": "PMID:22925", "title": "PH and the effect of fluoride and zinc on protein and collagen biosynthesis in rabbit dental pulp in vitro.", "content": "The effect of pH in the range 6.6-8.2 on the incorporation of 14C-proline into the rabbit dental pulp incubated in vitro has been studied. The amount of label in the cold TCA-soluble pool, total protein, and hydroxyproline (i.e. collagen) of the pulp tissue increased linearly with pH in all three fractions. A similar increase was found in the amount of labeled total protein and collagen recovered from the incubation medium. The results indicated that the uptake of 14C-proline into the TCA-soluble pool was the pH-sensitive step, whereas the incorporation into protein, formation of hydroxyproline, and the release of labeled macromolecules into the medium were not affected to any measurable degree by the ambient pH. In this system, zinc (60 micrometer) had less effect on the incorporation of 14C-proline into the different fractions of the pulp tissue at pH 6.6 as compared with pH 7.4, whereas with fluoride (1.3 mM) an increased inhibition of the uptake of 14C-proline into the TCA-soluble pool and the incorporation into total protein was found upon lowering the pH to 6.8. The inhibitory effect of zinc and fluoride on the release of labeled total protein and collagen into the incubation medium was not affected when the pH was lowered.", "contents": "PH and the effect of fluoride and zinc on protein and collagen biosynthesis in rabbit dental pulp in vitro. The effect of pH in the range 6.6-8.2 on the incorporation of 14C-proline into the rabbit dental pulp incubated in vitro has been studied. The amount of label in the cold TCA-soluble pool, total protein, and hydroxyproline (i.e. collagen) of the pulp tissue increased linearly with pH in all three fractions. A similar increase was found in the amount of labeled total protein and collagen recovered from the incubation medium. The results indicated that the uptake of 14C-proline into the TCA-soluble pool was the pH-sensitive step, whereas the incorporation into protein, formation of hydroxyproline, and the release of labeled macromolecules into the medium were not affected to any measurable degree by the ambient pH. In this system, zinc (60 micrometer) had less effect on the incorporation of 14C-proline into the different fractions of the pulp tissue at pH 6.6 as compared with pH 7.4, whereas with fluoride (1.3 mM) an increased inhibition of the uptake of 14C-proline into the TCA-soluble pool and the incorporation into total protein was found upon lowering the pH to 6.8. The inhibitory effect of zinc and fluoride on the release of labeled total protein and collagen into the incubation medium was not affected when the pH was lowered."}
{"id": "PMID:22926", "title": "Toxicity of some dental cements in a cell culture system.", "content": "A cell culture method has been used to study the effect of zinc phosphate cement (De Trey's Zinc Zement Improved), zinc silicophosphate cement (Fluoro-Thin) and polycarboxylate cement (Durelon) on animal cells. Disks (20 x 1 mm) of the materials were placed in the center of plastic Petri dishes and subsequently incubated with human epithelial cells. Cell multiplication, medium pH and the release of cement constituents were measured. All three cements exhibited a cytotoxic effect, which was most pronounced in the cultures with zinc silicophosphate cement and polycarboxylate cement. The results also indicated that cell growth on the surface of the disks is a more sensitive indicator of cytotoxicity than cell growth around the disks. pH of the medium was only slightly affected in cultures with polycarboxylate cement, whereas a decrease was found in cultures with zinc phosphate cement and especially with zinc silicophosphate cement. A rapid release of phosphate was found in cultures with zinc silicophosphate cement. Zinc was released into the medium from disks of zinc phosphate cement, zinc silicophosphate cement and polycarboxylate cement--exceeding the toxicity level for the present cell line after 24 h. In cultures with zinc silicophosphate cement and polycarboxylate cement the release of fluoride reached toxic levels within the same time interval.", "contents": "Toxicity of some dental cements in a cell culture system. A cell culture method has been used to study the effect of zinc phosphate cement (De Trey's Zinc Zement Improved), zinc silicophosphate cement (Fluoro-Thin) and polycarboxylate cement (Durelon) on animal cells. Disks (20 x 1 mm) of the materials were placed in the center of plastic Petri dishes and subsequently incubated with human epithelial cells. Cell multiplication, medium pH and the release of cement constituents were measured. All three cements exhibited a cytotoxic effect, which was most pronounced in the cultures with zinc silicophosphate cement and polycarboxylate cement. The results also indicated that cell growth on the surface of the disks is a more sensitive indicator of cytotoxicity than cell growth around the disks. pH of the medium was only slightly affected in cultures with polycarboxylate cement, whereas a decrease was found in cultures with zinc phosphate cement and especially with zinc silicophosphate cement. A rapid release of phosphate was found in cultures with zinc silicophosphate cement. Zinc was released into the medium from disks of zinc phosphate cement, zinc silicophosphate cement and polycarboxylate cement--exceeding the toxicity level for the present cell line after 24 h. In cultures with zinc silicophosphate cement and polycarboxylate cement the release of fluoride reached toxic levels within the same time interval."}
{"id": "PMID:22923", "title": "Effect of \"APUD\"-type hormones on osteolysis in vitro.", "content": "Besides their well-known actions, glucagon, ACTH, pentagastrin and insulin from the APUD series exert a direct action on the bone calcium content. Incubation with these substances of rat calvaria in vitro yields an evident stimulation of osteolysis with ACTH. Pentagastrin inhibits osteolysis. Glucagon and insulin inhibit parathormone-stimulated osteolysis, with no influence on the spontaneous one. Glucagon, resembling calcitonin, stimulates the 45Ca uptake from the incubation medium. The action of these substances completes the series of hormones influencing bone calcium metabolism, underlining possible interference actions of APUD-type hormones.", "contents": "Effect of \"APUD\"-type hormones on osteolysis in vitro. Besides their well-known actions, glucagon, ACTH, pentagastrin and insulin from the APUD series exert a direct action on the bone calcium content. Incubation with these substances of rat calvaria in vitro yields an evident stimulation of osteolysis with ACTH. Pentagastrin inhibits osteolysis. Glucagon and insulin inhibit parathormone-stimulated osteolysis, with no influence on the spontaneous one. Glucagon, resembling calcitonin, stimulates the 45Ca uptake from the incubation medium. The action of these substances completes the series of hormones influencing bone calcium metabolism, underlining possible interference actions of APUD-type hormones."}
{"id": "PMID:22927", "title": "Characterization of the beta-adrenergic receptors in the lower urinary tract of the cat.", "content": "The corpus-fundus and the outlet region of the urinary bladder of the cat was studied in vitro to characterize the beta-adrenergic receptors. In the corpus-fundus only beta1-receptors were found in contrast to the outlet region where the beta-receptors had both beta1-and beta2-characteristics.", "contents": "Characterization of the beta-adrenergic receptors in the lower urinary tract of the cat. The corpus-fundus and the outlet region of the urinary bladder of the cat was studied in vitro to characterize the beta-adrenergic receptors. In the corpus-fundus only beta1-receptors were found in contrast to the outlet region where the beta-receptors had both beta1-and beta2-characteristics."}
{"id": "PMID:22928", "title": "Polyarteritis nodosa of the penis.", "content": "The course of polyarteritis nodosa in a patient showing an isolated nodule localized to the glans penis is described. The underlying disease was not recognised and the patient was wrongly thought to have a penile cancer. Treatment with radiotherapy and Bleomycin had no effect and he subsequently died in uraemia. Postmortem examination revealed polyarteritis nodosa involving the kidneys and also causing localized changes to the glans penis.", "contents": "Polyarteritis nodosa of the penis. The course of polyarteritis nodosa in a patient showing an isolated nodule localized to the glans penis is described. The underlying disease was not recognised and the patient was wrongly thought to have a penile cancer. Treatment with radiotherapy and Bleomycin had no effect and he subsequently died in uraemia. Postmortem examination revealed polyarteritis nodosa involving the kidneys and also causing localized changes to the glans penis."}
{"id": "PMID:22932", "title": "Phosphorylated proteins as physiological effectors.", "content": "A variety of neurotransmitters, hormones, and other regulatory agents affect the phosphorylation of specific proteins in their target tissues. The types of stimuli that share this common effect on protein phosphorylation include numerous substances that do not act through cyclic AMP. These and other observations suggest that many different classes of regulatory substances achieve certain of their biological effects by altering the phosphorylation of specific proteins.", "contents": "Phosphorylated proteins as physiological effectors. A variety of neurotransmitters, hormones, and other regulatory agents affect the phosphorylation of specific proteins in their target tissues. The types of stimuli that share this common effect on protein phosphorylation include numerous substances that do not act through cyclic AMP. These and other observations suggest that many different classes of regulatory substances achieve certain of their biological effects by altering the phosphorylation of specific proteins."}
{"id": "PMID:22933", "title": "Dopaminergic inhibition of adrenergic neurotransmission as a model for studies on dopamine receptor mechanisms.", "content": "Dopamine and apomorphine produced concentration-dependent inhibition of adrenergic neurotransmission in the isolated, perfused, rabbit ear artery. The inhibitory action of both dopamine and apomorphine was competitively antagonized by haloperidol and several other antipsychotic drugs. The calculated affinities of these drugs for the dopaminergic receptor correlate closely with both the pharmacological potencies of these drugs in vivo and their reported potencies as inhibitors of [3H]haloperidol binding to \"dopamine receptors\" in brain homogenates.", "contents": "Dopaminergic inhibition of adrenergic neurotransmission as a model for studies on dopamine receptor mechanisms. Dopamine and apomorphine produced concentration-dependent inhibition of adrenergic neurotransmission in the isolated, perfused, rabbit ear artery. The inhibitory action of both dopamine and apomorphine was competitively antagonized by haloperidol and several other antipsychotic drugs. The calculated affinities of these drugs for the dopaminergic receptor correlate closely with both the pharmacological potencies of these drugs in vivo and their reported potencies as inhibitors of [3H]haloperidol binding to \"dopamine receptors\" in brain homogenates."}
{"id": "PMID:22935", "title": "Recent advances in alcohol withdrawal states.", "content": "Recent advances in alcohol withdrawal states are described. New concepts of classification, the development of the syndrome and its management are outlined. In the light of recent research, more optimistic results for this much maligned but common condition may be achieved.", "contents": "Recent advances in alcohol withdrawal states. Recent advances in alcohol withdrawal states are described. New concepts of classification, the development of the syndrome and its management are outlined. In the light of recent research, more optimistic results for this much maligned but common condition may be achieved."}
{"id": "PMID:22939", "title": "Chronotropism and blood flow patterns following teratogenic doses of catecholamines in 5-day-old chick embryos.", "content": "In vivo heart rates of 5-day-old chick embryos were recorded from electrodes placed in close proximity to the heart. L-epinephrine (4X10(-10) mole), 1-norepinephrine (1X10(-9)mole) and 1-isoproterenol (1.6X10(-10)mole) in 5 microliter of isotonic saline transiently accerlerated the mean heart rate by almost 9 percent. L-phenylephrine (2X10(-9)mole/5microliter) and the experimental procedure produced no appreciable effect. The positive chronotropic effect of the catecholamines was found to be highly significant (P less than 0.0005) as computed by Student's t test. However, no direct relationship could be established between the chronotropic response and the aortic arch anomalies produced. A prolonged reduction of blood flow in the primitive heart tube and the sixth aortic arch after administration of epinephrine and isoproterenol is apparently related to the induction of hypoplastic right pulmonary artery with absent or hypoplastic right ductus arteriosus.", "contents": "Chronotropism and blood flow patterns following teratogenic doses of catecholamines in 5-day-old chick embryos. In vivo heart rates of 5-day-old chick embryos were recorded from electrodes placed in close proximity to the heart. L-epinephrine (4X10(-10) mole), 1-norepinephrine (1X10(-9)mole) and 1-isoproterenol (1.6X10(-10)mole) in 5 microliter of isotonic saline transiently accerlerated the mean heart rate by almost 9 percent. L-phenylephrine (2X10(-9)mole/5microliter) and the experimental procedure produced no appreciable effect. The positive chronotropic effect of the catecholamines was found to be highly significant (P less than 0.0005) as computed by Student's t test. However, no direct relationship could be established between the chronotropic response and the aortic arch anomalies produced. A prolonged reduction of blood flow in the primitive heart tube and the sixth aortic arch after administration of epinephrine and isoproterenol is apparently related to the induction of hypoplastic right pulmonary artery with absent or hypoplastic right ductus arteriosus."}
{"id": "PMID:22941", "title": "5alpha-Pregna-1,20-dien-3-one and related compounds from a soft coral.", "content": "Four unusual pregnane derivatives, 5alpha-pregna-1,20-dien-3-one (1), 1,4,20-pregnatrien-3-one (3), 5alpha-pregn-20-en-3alpha-o1 o-acetate (4), and 5alpha-pregn-20-en-1alpha,3alpha-diol 3-acetate (6) have been isolated from an unidentified soft coral from Canton Island.", "contents": "5alpha-Pregna-1,20-dien-3-one and related compounds from a soft coral. Four unusual pregnane derivatives, 5alpha-pregna-1,20-dien-3-one (1), 1,4,20-pregnatrien-3-one (3), 5alpha-pregn-20-en-3alpha-o1 o-acetate (4), and 5alpha-pregn-20-en-1alpha,3alpha-diol 3-acetate (6) have been isolated from an unidentified soft coral from Canton Island."}
{"id": "PMID:22942", "title": "Culture of malaria parasites.", "content": "A human malaria vaccine that will protect against the blood stages of Plasmodium falciparum is dependent upon the continuous cultre of the parasite. Scientists have demonstrated that it is now possible to achieve this on a small scale. Present expertise needs to be expanded to produce larger quantities of material for antigenic studies and potential vaccine production.", "contents": "Culture of malaria parasites. A human malaria vaccine that will protect against the blood stages of Plasmodium falciparum is dependent upon the continuous cultre of the parasite. Scientists have demonstrated that it is now possible to achieve this on a small scale. Present expertise needs to be expanded to produce larger quantities of material for antigenic studies and potential vaccine production."}
{"id": "PMID:22945", "title": "Marrow grafts between DLA-identical and homozygous unrelated dogs: evidence for an additional locus involved in graft-versus-host disease.", "content": "Marrow transplants were carried out between unrelated donor-recipient pairs of dogs that were homozygous and identical for DLA-A, B, C, and D, i.e., mutually nonreactive in mixed leukocyte culture. Recipients were conditioned for transplantation by 1,200 R of total body irradiation and then treated with intermittent methotrexate for 102 days in order to prevent or delay graft-versus-host disease (GVHD). Of 13 dogs that received transplants, 4 are surviving with good grafts and no GVHD for more than 12 to 20 minutes. Nine died, 6 with GVHD between days 26 and 141, 1 with wasting on day 65, 1 with interstitial pneumonia on day 83, and 1 with graft rejection on day 23. In comparison, the survival of 17 DLA-identical littermates treated in the same manner was significantly better with 16 surviving without GVHD (P less than 0.01), while the survival of 54 DLA-nonidentical littermates was significantly worse with only two surviving without GVHD (P less than 0.025). These results are incompatible with the concept that solely the loci detected by mixed leukocyte culture and serotyping are responsible for GVHD. One or more additional loci appear to be involved. Knowledg e of this locus (loci) is important if marrow grafting between unrelated individuals is to be successful. However, results also indicate that an unrelated \"compatible\" marrow graft is more likely to succeed than a graft from an incompatible littermate.", "contents": "Marrow grafts between DLA-identical and homozygous unrelated dogs: evidence for an additional locus involved in graft-versus-host disease. Marrow transplants were carried out between unrelated donor-recipient pairs of dogs that were homozygous and identical for DLA-A, B, C, and D, i.e., mutually nonreactive in mixed leukocyte culture. Recipients were conditioned for transplantation by 1,200 R of total body irradiation and then treated with intermittent methotrexate for 102 days in order to prevent or delay graft-versus-host disease (GVHD). Of 13 dogs that received transplants, 4 are surviving with good grafts and no GVHD for more than 12 to 20 minutes. Nine died, 6 with GVHD between days 26 and 141, 1 with wasting on day 65, 1 with interstitial pneumonia on day 83, and 1 with graft rejection on day 23. In comparison, the survival of 17 DLA-identical littermates treated in the same manner was significantly better with 16 surviving without GVHD (P less than 0.01), while the survival of 54 DLA-nonidentical littermates was significantly worse with only two surviving without GVHD (P less than 0.025). These results are incompatible with the concept that solely the loci detected by mixed leukocyte culture and serotyping are responsible for GVHD. One or more additional loci appear to be involved. Knowledg e of this locus (loci) is important if marrow grafting between unrelated individuals is to be successful. However, results also indicate that an unrelated \"compatible\" marrow graft is more likely to succeed than a graft from an incompatible littermate."}
{"id": "PMID:22947", "title": "Analysis of the major histocompatibility complex in Syrian hamsters. I. Skin graft rejection, graft-versus-host reactions, mixed lymphocyte reactions, and immune response genes in inbred strains.", "content": "Five inbred strains of Syrian hamsters (Mesocricetus auratus) were examined for the presence of disparity at a genetic region similar to the major histocompatibility complex in other species. Vigorous reciprocal alloreactions developed in several strain combinations, which resulted in acute skin graft rejection, strong mixed lymphocyte reactions, and potent graft-versus-host reactions. In addition, we found evidence for an immune response gene which controls the antibody response to bovine serum albumin. Patterns of alloreactivity observed for skin graft rejection, graft-versus-host reactivity, and mixed lymphocyte reactivity are compatible with the hypothesis that hamsters possess a major histocompatibility complex, but the absence of discernable disparity at a serologically defined locus makes a definitive statement premature.", "contents": "Analysis of the major histocompatibility complex in Syrian hamsters. I. Skin graft rejection, graft-versus-host reactions, mixed lymphocyte reactions, and immune response genes in inbred strains. Five inbred strains of Syrian hamsters (Mesocricetus auratus) were examined for the presence of disparity at a genetic region similar to the major histocompatibility complex in other species. Vigorous reciprocal alloreactions developed in several strain combinations, which resulted in acute skin graft rejection, strong mixed lymphocyte reactions, and potent graft-versus-host reactions. In addition, we found evidence for an immune response gene which controls the antibody response to bovine serum albumin. Patterns of alloreactivity observed for skin graft rejection, graft-versus-host reactivity, and mixed lymphocyte reactivity are compatible with the hypothesis that hamsters possess a major histocompatibility complex, but the absence of discernable disparity at a serologically defined locus makes a definitive statement premature."}
{"id": "PMID:22948", "title": "Analysis of the major histocompatibility complex in Syrian hamsters. II. Linkage studies.", "content": "The genetic control of the histocompatibility antigens that induce strong alloreactions in Syrian hamsters was examined. Genetic studies revealed that the alloantigens involved in skin graft rejection, graft-versus-host reactions, and mixed lymphocyte reactions are under dominant single gene control and that these genetic loci are closely linked. These data suggest that this strong histocompatibility locus (i) may represent the major histocompatibility complex equivalent in this species, and this locus or group of loci has been called Hm-1. In addition, studies concerning the genetic control of the immune response to bovine serum albumin suggest that the high response is under dominant, single gene control; however, this gene is not linked to Hm-1.", "contents": "Analysis of the major histocompatibility complex in Syrian hamsters. II. Linkage studies. The genetic control of the histocompatibility antigens that induce strong alloreactions in Syrian hamsters was examined. Genetic studies revealed that the alloantigens involved in skin graft rejection, graft-versus-host reactions, and mixed lymphocyte reactions are under dominant single gene control and that these genetic loci are closely linked. These data suggest that this strong histocompatibility locus (i) may represent the major histocompatibility complex equivalent in this species, and this locus or group of loci has been called Hm-1. In addition, studies concerning the genetic control of the immune response to bovine serum albumin suggest that the high response is under dominant, single gene control; however, this gene is not linked to Hm-1."}
{"id": "PMID:22949", "title": "Secretion of various antimicrobial substances in dogs with experimental bacterial prostatitis.", "content": "Bacterial prostatitis in dogs was induced by injection of an E. coli 06 suspension into a branch of the prostatic artery. Three to six days later, secretion from the inflamed glands was obtained by pilocarpine stimulation and the concentrations of trimethoprim, sulphamethoxazole, erythromycin, doxycycline and ampicillin were measured during constant infusion of these drugs. In the prostatic secretion, only the concentrations of the lipid soluble substances trimethoprim and erythromycin exceeded the corresponding plasma levels. These two substances may therefore be of value in the treatment of bacterial prostatitis.", "contents": "Secretion of various antimicrobial substances in dogs with experimental bacterial prostatitis. Bacterial prostatitis in dogs was induced by injection of an E. coli 06 suspension into a branch of the prostatic artery. Three to six days later, secretion from the inflamed glands was obtained by pilocarpine stimulation and the concentrations of trimethoprim, sulphamethoxazole, erythromycin, doxycycline and ampicillin were measured during constant infusion of these drugs. In the prostatic secretion, only the concentrations of the lipid soluble substances trimethoprim and erythromycin exceeded the corresponding plasma levels. These two substances may therefore be of value in the treatment of bacterial prostatitis."}
{"id": "PMID:22950", "title": "[The passage of nitrogenous compounds through the wall of perfused sheep rumen (author's transl)].", "content": "Experiments were performed by the method of the extracorporeal perfusion of sheep rumen lasting 150 minutes. After 60 minutes of perfusion, 20 g of enzymatic casein hydrolyzate were applied to the rumen. Ammonia, urea, and total nitrogen were determined in the samples of perfusate, and ammonia and pH were determined in the rumen content. Considerable amounts of ammonia accumulated in the perfusate in the course of the experiment. At the end of perfusion, the concentration of NH3-N reached an average value of up to 12 mg per 100 ml. The level of urea in the perfusate decreased only in the first phase of perfusion (before the application of casein hydrolyzate to the rumen) and remained unchanged in the subsequent phase. It is assumed that part of urea-N from the perfusate after urea hydrolysis, taking place already in the rumen wall, returned to the perfusate in the form of ammonia. In the first phase of perfusion the passage of nitrogen from the blood into the rumen took place, in the second phase its absorption from the rumen into the blood was observed. The urea-N ratio from the passage of total nitrogen into the rumen ranged between 4.63% and 13.84%, but the concentration of total nitrogen in the perfusate decreased by 7-15% and that of urea nitrogen by 37-42%. It follows from the results that a major part of endogenous nitrogen passing from perfusate to the rumen was represented by proteins and/or their peptidic splits.", "contents": "[The passage of nitrogenous compounds through the wall of perfused sheep rumen (author's transl)]. Experiments were performed by the method of the extracorporeal perfusion of sheep rumen lasting 150 minutes. After 60 minutes of perfusion, 20 g of enzymatic casein hydrolyzate were applied to the rumen. Ammonia, urea, and total nitrogen were determined in the samples of perfusate, and ammonia and pH were determined in the rumen content. Considerable amounts of ammonia accumulated in the perfusate in the course of the experiment. At the end of perfusion, the concentration of NH3-N reached an average value of up to 12 mg per 100 ml. The level of urea in the perfusate decreased only in the first phase of perfusion (before the application of casein hydrolyzate to the rumen) and remained unchanged in the subsequent phase. It is assumed that part of urea-N from the perfusate after urea hydrolysis, taking place already in the rumen wall, returned to the perfusate in the form of ammonia. In the first phase of perfusion the passage of nitrogen from the blood into the rumen took place, in the second phase its absorption from the rumen into the blood was observed. The urea-N ratio from the passage of total nitrogen into the rumen ranged between 4.63% and 13.84%, but the concentration of total nitrogen in the perfusate decreased by 7-15% and that of urea nitrogen by 37-42%. It follows from the results that a major part of endogenous nitrogen passing from perfusate to the rumen was represented by proteins and/or their peptidic splits."}
{"id": "PMID:22952", "title": "[HCO3-stimulated adenosine triphosphatase in rat ovarian tumor cells].", "content": "Dependence of the HCO--3-stimulated ATPase activity from nuclei and mitochondria of rat ovary ascites tumor cells on pH and concentration of bicarbonate ions was studied. PCMB, NaN3, NaCNS, NaClO4 and NaF inhibited the HCO--3-stimulated ATPase activity. The properties of HCO--3-sensitive ATPase from rat ovary ascites tumor cells were similar to that of HCO--3-ATPases from other tissues.", "contents": "[HCO3-stimulated adenosine triphosphatase in rat ovarian tumor cells]. Dependence of the HCO--3-stimulated ATPase activity from nuclei and mitochondria of rat ovary ascites tumor cells on pH and concentration of bicarbonate ions was studied. PCMB, NaN3, NaCNS, NaClO4 and NaF inhibited the HCO--3-stimulated ATPase activity. The properties of HCO--3-sensitive ATPase from rat ovary ascites tumor cells were similar to that of HCO--3-ATPases from other tissues."}
{"id": "PMID:22953", "title": "[Role of adrenoreceptors in regulating aspartate aminotransferase isoenzyme activity in albino rat hearts].", "content": "Cytoplasmic (c) and mitochondrial (m) isoenzymes of aspartate aminotransferase (AAT, EC 2.6.1.1.) were isolated from rat heart extracts by electrophoresis in agar gel. Their pH optima and Km values were estimated; optimal conditions for estimation of the enzymatic activities are reported. Isadrine activated and adrenaline inhibited the cAAT activity. Noradrenaline did not affect the activity of both isoenzymes. Phentolamine, as contrary to obsidane which decreased the activity of both isoenzyme, activated the isoenzymes; the effect was partially decreased by obsidane. Phentolamine did not alter the noradrenaline effect on either mAAT or cAAT; it decreased significantly the free form of the mAAT activity only. Results of the experiments with administration of adrenomimetic drugs suggested that adrenaline and noradrenaline-isadrine had different sites of attachment through which they mediated their action on aspartate aminotransferase in rat heart mitochondria.", "contents": "[Role of adrenoreceptors in regulating aspartate aminotransferase isoenzyme activity in albino rat hearts]. Cytoplasmic (c) and mitochondrial (m) isoenzymes of aspartate aminotransferase (AAT, EC 2.6.1.1.) were isolated from rat heart extracts by electrophoresis in agar gel. Their pH optima and Km values were estimated; optimal conditions for estimation of the enzymatic activities are reported. Isadrine activated and adrenaline inhibited the cAAT activity. Noradrenaline did not affect the activity of both isoenzymes. Phentolamine, as contrary to obsidane which decreased the activity of both isoenzyme, activated the isoenzymes; the effect was partially decreased by obsidane. Phentolamine did not alter the noradrenaline effect on either mAAT or cAAT; it decreased significantly the free form of the mAAT activity only. Results of the experiments with administration of adrenomimetic drugs suggested that adrenaline and noradrenaline-isadrine had different sites of attachment through which they mediated their action on aspartate aminotransferase in rat heart mitochondria."}
{"id": "PMID:22954", "title": "[Anion-sensitive nuclear ATPase of the rat heart].", "content": "Properties of HCO--3-stimulated ATPase from rat heart muscle nuclei were studied. The maximal activity of HCO--3-ATPase was observed at concentration of bicarbonate 25 mM. The enzyme had a pH optimum at pH 8.0-8.5. Bicarbonate stimulated the ATPase activity only in presence of Mg2+, Mn2+ and Zn2+, Co2+, Cd2+ and Ca2+ were ineffective. NaCO3 and Na2SO3 at concentration 30 mM stimulated the nuclear ATPase activity by 20% and 81%, respectively. Anions N3--, scn--, clO--4, and I-- inhibited both Mg2+-ATPase and HCO--3-ATPase. HSO--3 and SO2--4 ions did not affect the nuclear ATPase activity.", "contents": "[Anion-sensitive nuclear ATPase of the rat heart]. Properties of HCO--3-stimulated ATPase from rat heart muscle nuclei were studied. The maximal activity of HCO--3-ATPase was observed at concentration of bicarbonate 25 mM. The enzyme had a pH optimum at pH 8.0-8.5. Bicarbonate stimulated the ATPase activity only in presence of Mg2+, Mn2+ and Zn2+, Co2+, Cd2+ and Ca2+ were ineffective. NaCO3 and Na2SO3 at concentration 30 mM stimulated the nuclear ATPase activity by 20% and 81%, respectively. Anions N3--, scn--, clO--4, and I-- inhibited both Mg2+-ATPase and HCO--3-ATPase. HSO--3 and SO2--4 ions did not affect the nuclear ATPase activity."}
{"id": "PMID:22958", "title": "[Long-term treatment with the new antiarrhythmic drug propafenone in correlation to plasma levels (author's transl)].", "content": "The results of long term oral therapy of cardiac arrhythmias in 43 patients successfully treated with propafenone are reported. The patients were treated for periods ranging between 1 month and 34 months with a mean of 13.4 months. The administered dose varied between 150 mg tds and 300 mg qds with an average daily dose of between 600 and 750 mg. The doses were decided on a body-weight basis with range of 6 to 17 mg/kg and an average of 12 mg/kg. Altogether 30 patients were successfully treated over a long period, sometimes in combination with other antiarrhythmic agents, particularly beta-blockers. 2 patients did not appear after some first controls. In 7 patients the drug was not effective, even when used in combination with others. 4 patients stopped the treatment due to side-effects. Further 18 patients complained temporarily of gastrointestinal and cerebral side-effects. Some Ecg changes were noted, particularly A-V conduction delays and spreading of the QRS-complex. We suggest that the clinically most important parameters for monitoring an antiarrhythmic regimen of propafenone are the patients's own history and Ecg-examination noting the PQ interval and particularly the width of the QRS-complex and long-term monitoring.", "contents": "[Long-term treatment with the new antiarrhythmic drug propafenone in correlation to plasma levels (author's transl)]. The results of long term oral therapy of cardiac arrhythmias in 43 patients successfully treated with propafenone are reported. The patients were treated for periods ranging between 1 month and 34 months with a mean of 13.4 months. The administered dose varied between 150 mg tds and 300 mg qds with an average daily dose of between 600 and 750 mg. The doses were decided on a body-weight basis with range of 6 to 17 mg/kg and an average of 12 mg/kg. Altogether 30 patients were successfully treated over a long period, sometimes in combination with other antiarrhythmic agents, particularly beta-blockers. 2 patients did not appear after some first controls. In 7 patients the drug was not effective, even when used in combination with others. 4 patients stopped the treatment due to side-effects. Further 18 patients complained temporarily of gastrointestinal and cerebral side-effects. Some Ecg changes were noted, particularly A-V conduction delays and spreading of the QRS-complex. We suggest that the clinically most important parameters for monitoring an antiarrhythmic regimen of propafenone are the patients's own history and Ecg-examination noting the PQ interval and particularly the width of the QRS-complex and long-term monitoring."}
{"id": "PMID:22955", "title": "[Depression of rat liver acetyl-CoA-carboxylase activity by salicylate and other compounds].", "content": "Two intraperitoneal injections of salicylate at a dose of 250 mg/kg of body weight led to decrease in the acetyl-CoA-carboxylase activity in liver soluble fraction (140000xg) more than by 60%. Salicylate in concentrations 10(-4) and 10(-2) M inhibited the enzyme from rat liver soluble fraction by 25% and 80%, respectively, in vitro: it was found to be as effective inhibitor as kynurenate and clofibrate. Derivatives of salicylate -- acetyl salicylate and salicyl amide also showed this inhibitory effect, but their action was less disinct as compared with salicylate. 2-phenyl-3-methyl-hydroxypentanic and 2,3-diphenyl-3-hydroxypentanic acids (derivatives of deoxymevalonic acid) demonstrated the strong inhibitory effect on acetyl-CoA-carboxylase, comparable to the action of salicylate. The effect of salicylate on the reaction of carboxylation was not related to competition for acetyl-CoA (formation of acetyl salicylate), to interaction with biotin and to allosteric reaction with acetyl-CoA-carboxylase. Possible mechanisms of the salicylate effect on the enzyme activity are discussed.", "contents": "[Depression of rat liver acetyl-CoA-carboxylase activity by salicylate and other compounds]. Two intraperitoneal injections of salicylate at a dose of 250 mg/kg of body weight led to decrease in the acetyl-CoA-carboxylase activity in liver soluble fraction (140000xg) more than by 60%. Salicylate in concentrations 10(-4) and 10(-2) M inhibited the enzyme from rat liver soluble fraction by 25% and 80%, respectively, in vitro: it was found to be as effective inhibitor as kynurenate and clofibrate. Derivatives of salicylate -- acetyl salicylate and salicyl amide also showed this inhibitory effect, but their action was less disinct as compared with salicylate. 2-phenyl-3-methyl-hydroxypentanic and 2,3-diphenyl-3-hydroxypentanic acids (derivatives of deoxymevalonic acid) demonstrated the strong inhibitory effect on acetyl-CoA-carboxylase, comparable to the action of salicylate. The effect of salicylate on the reaction of carboxylation was not related to competition for acetyl-CoA (formation of acetyl salicylate), to interaction with biotin and to allosteric reaction with acetyl-CoA-carboxylase. Possible mechanisms of the salicylate effect on the enzyme activity are discussed."}
{"id": "PMID:22956", "title": "[Tyrosine-alpha-ketoglutarate transaminase activity in the rat liver after partial hepatectomy and CCl4 poisoning].", "content": "Acitivity of tyrosine-alpha-ketoglutarate transaminase and induction of the enzyme by hydro cortisone were studied in rat liver tissue after partial hepatectomy and intoxication with CCl4 Administration of the hormone increased the enzymatic activity within 72 hrs after treatment with CCl4 but did not affect its value within 8 and 24 hrs. Activation of the enzyme by hydrocortisone correlated with the increased enzymatic activity observed within 20 hrs after partial hepatectomy. Possible mechanisms for activation of the enzyme, caused by endo- and exogenous factors, are discussed.", "contents": "[Tyrosine-alpha-ketoglutarate transaminase activity in the rat liver after partial hepatectomy and CCl4 poisoning]. Acitivity of tyrosine-alpha-ketoglutarate transaminase and induction of the enzyme by hydro cortisone were studied in rat liver tissue after partial hepatectomy and intoxication with CCl4 Administration of the hormone increased the enzymatic activity within 72 hrs after treatment with CCl4 but did not affect its value within 8 and 24 hrs. Activation of the enzyme by hydrocortisone correlated with the increased enzymatic activity observed within 20 hrs after partial hepatectomy. Possible mechanisms for activation of the enzyme, caused by endo- and exogenous factors, are discussed."}
{"id": "PMID:22960", "title": "Chemical stimulation of Schistosoma mansoni miracidial activity.", "content": "The movements of S. mansoni miracidia immersed in various solutions of organic chemicals were recorded by dark ground photography. Reduction of miracidial speed was recorded for miracidia in solutions of fatty acids and ammonia. The speed reduction was concentration dependant and pH dependant, indicating in both cases that the un-ionized molecule was responsible. Ammonia at concentrations between 0.4 mM and 0.8 mM elicited an increased \"rate of change of direction\" by miracidia. No changes in miracidial movements were recorded for miracidia immersed in aqueous solutions of amino acids, sugars or of molluscan nitrogenous excretion products other than ammonia. A possible role for chemo-klinokinetic behaviour patterns in miracidial host location was formulated.", "contents": "Chemical stimulation of Schistosoma mansoni miracidial activity. The movements of S. mansoni miracidia immersed in various solutions of organic chemicals were recorded by dark ground photography. Reduction of miracidial speed was recorded for miracidia in solutions of fatty acids and ammonia. The speed reduction was concentration dependant and pH dependant, indicating in both cases that the un-ionized molecule was responsible. Ammonia at concentrations between 0.4 mM and 0.8 mM elicited an increased \"rate of change of direction\" by miracidia. No changes in miracidial movements were recorded for miracidia immersed in aqueous solutions of amino acids, sugars or of molluscan nitrogenous excretion products other than ammonia. A possible role for chemo-klinokinetic behaviour patterns in miracidial host location was formulated."}
{"id": "PMID:22962", "title": "[Thermostable basic proteinase inhibitors from potatoes. Isolation and characterization (author's transl)].", "content": "Four basic proteinase inhibitors were isolated from potato tubers (var. Maritta) by ammonium sulfate precipitation, heat treatment, chromatography on CM-cellulose and preparative polyacrylamide gel electrophoresis. Their isoelectric points are in the pH range 9.2--9.8. The molecular weights, as estimated by Sephadex gel filtration, were 8500 for inhibitor K 1 and 22000 for the inhibitors K3, K4, and K6. Differences in inhibitors regarding amino acid composition and specific activity against six different proteinases are discussed. Comparisons with previously described inhibitors are given. A correlation between high cystine content and thermostability of the inhibitor proteins is indicated.", "contents": "[Thermostable basic proteinase inhibitors from potatoes. Isolation and characterization (author's transl)]. Four basic proteinase inhibitors were isolated from potato tubers (var. Maritta) by ammonium sulfate precipitation, heat treatment, chromatography on CM-cellulose and preparative polyacrylamide gel electrophoresis. Their isoelectric points are in the pH range 9.2--9.8. The molecular weights, as estimated by Sephadex gel filtration, were 8500 for inhibitor K 1 and 22000 for the inhibitors K3, K4, and K6. Differences in inhibitors regarding amino acid composition and specific activity against six different proteinases are discussed. Comparisons with previously described inhibitors are given. A correlation between high cystine content and thermostability of the inhibitor proteins is indicated."}
{"id": "PMID:22964", "title": "[Aqueous chloride and bromine solutions as disinfectants: composition, redox potential, differences of reactivity (author's transl)].", "content": "A method is given to calculate the equilibrium concentrations of the molecules and ions emerging from the hydrolysis and dissociation of chlorine and bromine in aqueous soltuion. The differing influence the pH value and the initial (total) halogene concentration exerts to the HOX- and X2-equilibrium concentration is discussed. From the calculated equilibrium concentrations and tabulated standard reduction potentials the redox potentials of chlorine and bromine solutions at various pH values are calculated. No correlation between the reactivity and the redox potential of the two halogens was observed. Two possible explanations for the differing reactivity of chlorine and bromine against proteins are presented.", "contents": "[Aqueous chloride and bromine solutions as disinfectants: composition, redox potential, differences of reactivity (author's transl)]. A method is given to calculate the equilibrium concentrations of the molecules and ions emerging from the hydrolysis and dissociation of chlorine and bromine in aqueous soltuion. The differing influence the pH value and the initial (total) halogene concentration exerts to the HOX- and X2-equilibrium concentration is discussed. From the calculated equilibrium concentrations and tabulated standard reduction potentials the redox potentials of chlorine and bromine solutions at various pH values are calculated. No correlation between the reactivity and the redox potential of the two halogens was observed. Two possible explanations for the differing reactivity of chlorine and bromine against proteins are presented."}
{"id": "PMID:22967", "title": "Some properties of the lipoxygenase from rabbit reticulocytes.", "content": "A lipoxygenase was enriched from the stoma-free supernatant of rabbit reticulocytes. The enzyme causes drastic deterioration of mitochondrial membranes. The release of matrix enzymes is paralleled by formation of products of lipid peroxidation. The enzyme reacts with isolated phospholipds and free cis-unsaturated fatty acids. Some properties were determined: molecular weight, isoelectric point, temperature and pH-dependence and Km value for linoleic acid. The enzyme is inhibited by reaction products and a variety of inhibitors, especially antioxidants and chelating agents.", "contents": "Some properties of the lipoxygenase from rabbit reticulocytes. A lipoxygenase was enriched from the stoma-free supernatant of rabbit reticulocytes. The enzyme causes drastic deterioration of mitochondrial membranes. The release of matrix enzymes is paralleled by formation of products of lipid peroxidation. The enzyme reacts with isolated phospholipds and free cis-unsaturated fatty acids. Some properties were determined: molecular weight, isoelectric point, temperature and pH-dependence and Km value for linoleic acid. The enzyme is inhibited by reaction products and a variety of inhibitors, especially antioxidants and chelating agents."}
{"id": "PMID:22969", "title": "Thermodynamics of red cell glycolysis.", "content": "1. Changes of Gibbs energy, enthalpy and entropy in red cells during steady-state glycolysis were discussed. 2. The heat production of red cells at various metabolic conditions was measured on a flow microcalorimeter with simultaneous analyses of lactate and other metabolites. The results were discussed in relation to enthalpy changes of the different metabolic steps in the glycolytic pathway.", "contents": "Thermodynamics of red cell glycolysis. 1. Changes of Gibbs energy, enthalpy and entropy in red cells during steady-state glycolysis were discussed. 2. The heat production of red cells at various metabolic conditions was measured on a flow microcalorimeter with simultaneous analyses of lactate and other metabolites. The results were discussed in relation to enthalpy changes of the different metabolic steps in the glycolytic pathway."}
{"id": "PMID:22970", "title": "pH-dependent changes of 2,3-bisphosphoglycerate.", "content": "A systematic study of the pH dependent changes in the range 6.6--7.4 of 2,3 bisphosphoglycerate (2,3-DPG) was performed in the presence and absence of glucose during transitional and steady states. The results indicate that 2,3-DPGase breaks down 2,3-DPG nealy independent of pH at a rate of 480 mu moles 2,3-DPG/1 cells.h. The 2,3-DPG mutase is practically completely inhibited below pH 6.9. The 2,3-DPG level in the presence of glucose reaches a pH dependent steady state after about 18 h. The share of the 2,3-DPG bypass in the steady state decreases from 24% at pH 7.4 to 12% at pH 7.0. The formation of pyruvate corresponds to the beadkdown of 2,3-DPG after consumption of an unknown reducing substance.", "contents": "pH-dependent changes of 2,3-bisphosphoglycerate. A systematic study of the pH dependent changes in the range 6.6--7.4 of 2,3 bisphosphoglycerate (2,3-DPG) was performed in the presence and absence of glucose during transitional and steady states. The results indicate that 2,3-DPGase breaks down 2,3-DPG nealy independent of pH at a rate of 480 mu moles 2,3-DPG/1 cells.h. The 2,3-DPG mutase is practically completely inhibited below pH 6.9. The 2,3-DPG level in the presence of glucose reaches a pH dependent steady state after about 18 h. The share of the 2,3-DPG bypass in the steady state decreases from 24% at pH 7.4 to 12% at pH 7.0. The formation of pyruvate corresponds to the beadkdown of 2,3-DPG after consumption of an unknown reducing substance."}
{"id": "PMID:22972", "title": "[Influence of bicarbonate on the content of 2,3-DPG (bisdihydroglycerophosphate) in preserved erythrocytes].", "content": "Both whole blood in ACD-adenine-guanosine solution (PCV about 36%) and resuspensions of erythrocytes from EDTA-blood (PCV about 80%) were stored at 4 degrees C with an admixture of sodium bicarbonate. To the resuspensions simultaneously were added xylitol and inorganic phosphate. The erythrocyte concentration of 2,3-disphosphoglycerate in whole blood will be preserved the longer the more bicarbonate is added. Compared with whole blood in resuspensions of erythrocytes the preservation of 2,3-DPG is significantly prolonged, probably because xylitol was added. From these results and from literature data it is concluded that bicarbonate is fixed to metabolites of the pentose metabolism. The products of the fixation of bicarbonate may influence the 2,3-DPG metabolism of the erythrocytes.", "contents": "[Influence of bicarbonate on the content of 2,3-DPG (bisdihydroglycerophosphate) in preserved erythrocytes]. Both whole blood in ACD-adenine-guanosine solution (PCV about 36%) and resuspensions of erythrocytes from EDTA-blood (PCV about 80%) were stored at 4 degrees C with an admixture of sodium bicarbonate. To the resuspensions simultaneously were added xylitol and inorganic phosphate. The erythrocyte concentration of 2,3-disphosphoglycerate in whole blood will be preserved the longer the more bicarbonate is added. Compared with whole blood in resuspensions of erythrocytes the preservation of 2,3-DPG is significantly prolonged, probably because xylitol was added. From these results and from literature data it is concluded that bicarbonate is fixed to metabolites of the pentose metabolism. The products of the fixation of bicarbonate may influence the 2,3-DPG metabolism of the erythrocytes."}
{"id": "PMID:22974", "title": "Experimental liver failure. A comparison between hepatectomy and hepatic devascularization in the pig.", "content": "Difficulties in the treatment of acute hepatic failure due to insufficient knowledge of the pathogenesis and the impredectability of the course has made an experimental model desirable. A number of such models have been proposed, among these hepatectomy and total hepatic devascularization. In the present study hepatectomy and total hepatic devascularization have been compared, as it has been doubted if hepatectomy, not including necrotic liver tissue, is a valid model of human hepatic failure. No significant difference was found in the survival time which was 16 h 2 min +/- 57 min in the anhepatic and 18 h 33 min +/- 1 h 5 min in the devascularized preparation. The blood pressure of the anhepatic preparation decreased gradually, in contrast that of the devascularized preparation remained stable during most of the experimental period with a terminal steep decrease. Except for an increase in serum alanin-aminotransferases and free hemoglobin, seen in the devascularized, but not in the anhepatic preparation, no differences between the two models were seen. It is concluded that the presence of necrotic tissue is of minor importance, but for technical reasons the devascularized preparation is the most suitable model for experimental hepatic failure.", "contents": "Experimental liver failure. A comparison between hepatectomy and hepatic devascularization in the pig. Difficulties in the treatment of acute hepatic failure due to insufficient knowledge of the pathogenesis and the impredectability of the course has made an experimental model desirable. A number of such models have been proposed, among these hepatectomy and total hepatic devascularization. In the present study hepatectomy and total hepatic devascularization have been compared, as it has been doubted if hepatectomy, not including necrotic liver tissue, is a valid model of human hepatic failure. No significant difference was found in the survival time which was 16 h 2 min +/- 57 min in the anhepatic and 18 h 33 min +/- 1 h 5 min in the devascularized preparation. The blood pressure of the anhepatic preparation decreased gradually, in contrast that of the devascularized preparation remained stable during most of the experimental period with a terminal steep decrease. Except for an increase in serum alanin-aminotransferases and free hemoglobin, seen in the devascularized, but not in the anhepatic preparation, no differences between the two models were seen. It is concluded that the presence of necrotic tissue is of minor importance, but for technical reasons the devascularized preparation is the most suitable model for experimental hepatic failure."}
{"id": "PMID:22975", "title": "Morphology, histochemistry and isozymes of monkey kidney cells during long-term exposure to cigarette smoke.", "content": "Monkey kidney cells (Vero) in monolayer culture were exposed to 260 puffs of whole smoke from a mid tar range cigarette over a period of 240 days. Cell morphology was investigated at the light and electron microscopic level. The histochemical characteristics of several hydrolytic enzymes and dehydrogenases were examined, and the isozymes of LDH, MDH and G6PD studied. For all these parameters smoke exposed cells displayed the same features as sham exposed and negative controls. The cells were assessed as non malignant by their failure to form tumours in the nude mouse.", "contents": "Morphology, histochemistry and isozymes of monkey kidney cells during long-term exposure to cigarette smoke. Monkey kidney cells (Vero) in monolayer culture were exposed to 260 puffs of whole smoke from a mid tar range cigarette over a period of 240 days. Cell morphology was investigated at the light and electron microscopic level. The histochemical characteristics of several hydrolytic enzymes and dehydrogenases were examined, and the isozymes of LDH, MDH and G6PD studied. For all these parameters smoke exposed cells displayed the same features as sham exposed and negative controls. The cells were assessed as non malignant by their failure to form tumours in the nude mouse."}
{"id": "PMID:22976", "title": "Physiologic evaluation of the HFPPV pneumatic valve principle and PEEP. An experimental study.", "content": "In experiments in dogs the ventilatory and circulatory conditions prevailing with the ventilatory pattern in high-frequency positive-pressure ventilation (HFPPV) were investigated with use of a pneumatic valve principle and a ventilator system of an \"open\" character. Keeping the gas input constant the importance of insufflation frequency and insufflation time and the reactions to various levels of positive end-expiratory pressure (PEEP) were investigated in terms of changes in arterial pH, Pco2 and Po2. With the volumes of delivered gas kept constant, an increasing insufflation frequency from 60 to 100 per min gave a parallel decrease in tidal volume accompanied by lower maximum intratracheal pressures and a significant decrease in alveolar ventilation. Also taking into account the possibilities of inducing a suppression of the spontaneous respiration, higher ventilatory frequencies than 60 per min do now seem to introduce any further advantages. Including the associated effects on cardiac output and venous admixture, the cardio-pulmonary and circulatory parameters studied did not show any substantial changes with PEEP levels below 7.5--10 cm H2O. Thus the level of PEEP, which often is part of the ventilatory pattern in HFPPV, does not seem to have any untoward influence on the circulation (stroke volume, cardiac output, total peripheral vascular resistance) and oxygen transport (arterial oxygen content and oxygen flux) in normovolaemic dogs.", "contents": "Physiologic evaluation of the HFPPV pneumatic valve principle and PEEP. An experimental study. In experiments in dogs the ventilatory and circulatory conditions prevailing with the ventilatory pattern in high-frequency positive-pressure ventilation (HFPPV) were investigated with use of a pneumatic valve principle and a ventilator system of an \"open\" character. Keeping the gas input constant the importance of insufflation frequency and insufflation time and the reactions to various levels of positive end-expiratory pressure (PEEP) were investigated in terms of changes in arterial pH, Pco2 and Po2. With the volumes of delivered gas kept constant, an increasing insufflation frequency from 60 to 100 per min gave a parallel decrease in tidal volume accompanied by lower maximum intratracheal pressures and a significant decrease in alveolar ventilation. Also taking into account the possibilities of inducing a suppression of the spontaneous respiration, higher ventilatory frequencies than 60 per min do now seem to introduce any further advantages. Including the associated effects on cardiac output and venous admixture, the cardio-pulmonary and circulatory parameters studied did not show any substantial changes with PEEP levels below 7.5--10 cm H2O. Thus the level of PEEP, which often is part of the ventilatory pattern in HFPPV, does not seem to have any untoward influence on the circulation (stroke volume, cardiac output, total peripheral vascular resistance) and oxygen transport (arterial oxygen content and oxygen flux) in normovolaemic dogs."}
{"id": "PMID:22979", "title": "Some effects of sugar-flavored acid beverages on the biochemistry of human whole saliva and dental plaque.", "content": "An investigation was made of the effects on some biochemical characteristics of human whole saliva and dental plaque resulting from the daily consumption of three commercial, acid-containing beverages. The beverages tested were a cola beverage (\"Coca-Cola\"), a carbonated orange drink (\"Jaffa\") and single strength orange juice. Each of the three test beverages as well as non-fluoridated tap water as a control, were consumed during four two-week periods. The test group consisted of 39 dental students. The mean consumption frequency lay in the range from 5.3 to 5.7 times per day. Orange juice was found to stimulate the salivary secretion rate most. All test drinks decreased the salivary pH immediately after consumption, but the pH did not generally drotase-like activity in oral fluid. Changes were observed in calcium, phosphate and fluoride concentrations in oral fluid samples, but these were due to variations in salivary secretion rate. A significant decrease in redox potentials of whole saliva was, however, observed after consumption of the drinks. The present results indicate that in healthy persons with normal saliva flow rate and buffer capacity the moderate consumption of acidic beverages failed to induce any remarkable caries-promoting changes in oral cavity. However, in persons with low salivary flow rate erosion may be a consequence of regular consumption.", "contents": "Some effects of sugar-flavored acid beverages on the biochemistry of human whole saliva and dental plaque. An investigation was made of the effects on some biochemical characteristics of human whole saliva and dental plaque resulting from the daily consumption of three commercial, acid-containing beverages. The beverages tested were a cola beverage (\"Coca-Cola\"), a carbonated orange drink (\"Jaffa\") and single strength orange juice. Each of the three test beverages as well as non-fluoridated tap water as a control, were consumed during four two-week periods. The test group consisted of 39 dental students. The mean consumption frequency lay in the range from 5.3 to 5.7 times per day. Orange juice was found to stimulate the salivary secretion rate most. All test drinks decreased the salivary pH immediately after consumption, but the pH did not generally drotase-like activity in oral fluid. Changes were observed in calcium, phosphate and fluoride concentrations in oral fluid samples, but these were due to variations in salivary secretion rate. A significant decrease in redox potentials of whole saliva was, however, observed after consumption of the drinks. The present results indicate that in healthy persons with normal saliva flow rate and buffer capacity the moderate consumption of acidic beverages failed to induce any remarkable caries-promoting changes in oral cavity. However, in persons with low salivary flow rate erosion may be a consequence of regular consumption."}
{"id": "PMID:22981", "title": "Kinetics of the binding of salicylazosulfapyridine to human serum albumin.", "content": "In order to elucidate the possibility of the dissociation rate of drugs from plasma proteins presenting a rate limiting step in the elimination of drugs by secretion (renal or biliary) and metabolism, the kinetics of salicylazosulfapyridine (SASP) binding to human serum albumin (HSA) has been investigated by stopped-flow photometry. Equilibrium dialysis showed that HSA has three classes of binding sites for SASP with 0.93, 2.3 and 8.4 sites, respectively, and association constants of 2.1.10(6), 1.4.10(5) and 3.0.10(3) M-1, respectively. The association rate constants for the first and second classes are 4.4.10(6) and 1.5.10(7) M-1 sec.-1, and the dissociation rate constants are 2.1 and 109 sec.-1. At SASP concentrations resulting from the usual therapeutic doses about 83% will bind to the first class binding sites. The dissociation \"half time\" for this class being 0.34 sec., leads to the conclusion that dissociation rates of this order of magnitude are unlikely to reduce the rate of metabolism or biliary secretion whereas it may reduce renal tubular secretion. Whether this is the case depends on the intrinsic rate constant of secretion.", "contents": "Kinetics of the binding of salicylazosulfapyridine to human serum albumin. In order to elucidate the possibility of the dissociation rate of drugs from plasma proteins presenting a rate limiting step in the elimination of drugs by secretion (renal or biliary) and metabolism, the kinetics of salicylazosulfapyridine (SASP) binding to human serum albumin (HSA) has been investigated by stopped-flow photometry. Equilibrium dialysis showed that HSA has three classes of binding sites for SASP with 0.93, 2.3 and 8.4 sites, respectively, and association constants of 2.1.10(6), 1.4.10(5) and 3.0.10(3) M-1, respectively. The association rate constants for the first and second classes are 4.4.10(6) and 1.5.10(7) M-1 sec.-1, and the dissociation rate constants are 2.1 and 109 sec.-1. At SASP concentrations resulting from the usual therapeutic doses about 83% will bind to the first class binding sites. The dissociation \"half time\" for this class being 0.34 sec., leads to the conclusion that dissociation rates of this order of magnitude are unlikely to reduce the rate of metabolism or biliary secretion whereas it may reduce renal tubular secretion. Whether this is the case depends on the intrinsic rate constant of secretion."}
{"id": "PMID:22982", "title": "Rapid gas chromatographic assay of serum diazepam, N-desmethyldiazepam, and N-desalkylflurazepam.", "content": "A rapid procedure for the measurement of serum diazepam (D), N-desmethyldiazepam (ND), and N-desalkylflurazepam (NF), levels in clinical samples is described. The single step extraction procedure yields quantitative extraction for the drugs mentioned above. No solvent evaporation step is needed. No interference of endogenous substances or generally used psychotropic drugs containing halogen atoms has been observed. The conditions provide excellent precision, due to a clear separation of the internal standard, medazepam, from the solvent front. The frequency response electron capture detector provides a linear response to the drugs over a 5 X 10(2) concentration range making serial dilution of the samples unnecessary. The automatic data reduction system indicates the serum levels directly in ng/ml without manual calculations.", "contents": "Rapid gas chromatographic assay of serum diazepam, N-desmethyldiazepam, and N-desalkylflurazepam. A rapid procedure for the measurement of serum diazepam (D), N-desmethyldiazepam (ND), and N-desalkylflurazepam (NF), levels in clinical samples is described. The single step extraction procedure yields quantitative extraction for the drugs mentioned above. No solvent evaporation step is needed. No interference of endogenous substances or generally used psychotropic drugs containing halogen atoms has been observed. The conditions provide excellent precision, due to a clear separation of the internal standard, medazepam, from the solvent front. The frequency response electron capture detector provides a linear response to the drugs over a 5 X 10(2) concentration range making serial dilution of the samples unnecessary. The automatic data reduction system indicates the serum levels directly in ng/ml without manual calculations."}
{"id": "PMID:22984", "title": "The effect of adrenaline on acetylcholine synthesis after blockade of alpha- and beta-adrenergic receptors in vitro.", "content": "The aim of the present work was to explain the mechanism of the stimulating effect of adrenaline (A) on acetylcholine (ACh) synthesis. This action is exerted most probably through the beta- adrenergic receptors, since propranolol and oxprenolol inhibit the stimulating effect of adrenaline on acetylcholine synthesis in the rat cerebral cortex in vitro. Dihydroergotamine does not show such effect. Practolol and phentolamine decrease the spontaneous synthesis of ACh in concentration several times lower than that inhibiting the ACh synthesis stimulated by adrenaline. It is suggested that adrenaline-induced stimulation of ACh synthesis in the rat cerebral cortex is not due to cyclic AMP, because noradrenaline (NA) does not increase ACh synthesis either in vivo or in vitro, although it activates the adenyl cyclase. NA on the other hand activates ACh synthesis in the calcium-free medium, which inhibits activating effect of NA on adenyl cyclase. Moreover it was found that cyclic AMP depresses ACh synthesis in the rat cerebral cortex in vitro.", "contents": "The effect of adrenaline on acetylcholine synthesis after blockade of alpha- and beta-adrenergic receptors in vitro. The aim of the present work was to explain the mechanism of the stimulating effect of adrenaline (A) on acetylcholine (ACh) synthesis. This action is exerted most probably through the beta- adrenergic receptors, since propranolol and oxprenolol inhibit the stimulating effect of adrenaline on acetylcholine synthesis in the rat cerebral cortex in vitro. Dihydroergotamine does not show such effect. Practolol and phentolamine decrease the spontaneous synthesis of ACh in concentration several times lower than that inhibiting the ACh synthesis stimulated by adrenaline. It is suggested that adrenaline-induced stimulation of ACh synthesis in the rat cerebral cortex is not due to cyclic AMP, because noradrenaline (NA) does not increase ACh synthesis either in vivo or in vitro, although it activates the adenyl cyclase. NA on the other hand activates ACh synthesis in the calcium-free medium, which inhibits activating effect of NA on adenyl cyclase. Moreover it was found that cyclic AMP depresses ACh synthesis in the rat cerebral cortex in vitro."}
{"id": "PMID:22988", "title": "Direct antilipolytic effect of acidosis in isolated rat adipocytes.", "content": "The possibility that acidosis inhibits lipolysis indirectly by causing ionic shifts or by favouring the accumulation of an inhibitor has been tested in isolated fat cells. Lipolysis induced by 3 muM noradrenaline (NA) was inhibited by 40-60% and that induced by 1 mM theophylline (THEO) by about 75% when the pH was reduced to 6.6. Lipolysis induced by NA + THEO was inhibited by 20-30%. Changing the concentration of Ca++ or Mg++ did not alter the degree of inhibition. Reducing the K+-ion concentration enhanced the inhibitory effect of low pH on lipolysis induced by NA or NA + THEO, whereas cyclic AMP accumulation was uninfluenced. Omitting glucose from the incubation medium caused a slight enhancement of pH-induced inhibition of lipolysis (from 60 to 70%, p less than 0.01). Reducing the concentration of albumin, which binds inhibitory substances such as FFA, reduced lipolysis more at normal than at reduced pH. At high FFA/albumin ratios (5 or above) lipolysis was similar at normal and reduced pH. The antilipolytic effect of decreased pH was equally pronounced in perifused fat cells, where inhibitory substances are not allowed to accumulate. Our results suggest that the antilipolytic effect of acidosis is mainly a direct effect of the increase in H+ ion concentration. The inhibitory effect of acidosis on various responses to beta-adrenoceptor stimulation may be caused by a decreased formation of cyclic AMP in turn caused directly by the decrease in pH.", "contents": "Direct antilipolytic effect of acidosis in isolated rat adipocytes. The possibility that acidosis inhibits lipolysis indirectly by causing ionic shifts or by favouring the accumulation of an inhibitor has been tested in isolated fat cells. Lipolysis induced by 3 muM noradrenaline (NA) was inhibited by 40-60% and that induced by 1 mM theophylline (THEO) by about 75% when the pH was reduced to 6.6. Lipolysis induced by NA + THEO was inhibited by 20-30%. Changing the concentration of Ca++ or Mg++ did not alter the degree of inhibition. Reducing the K+-ion concentration enhanced the inhibitory effect of low pH on lipolysis induced by NA or NA + THEO, whereas cyclic AMP accumulation was uninfluenced. Omitting glucose from the incubation medium caused a slight enhancement of pH-induced inhibition of lipolysis (from 60 to 70%, p less than 0.01). Reducing the concentration of albumin, which binds inhibitory substances such as FFA, reduced lipolysis more at normal than at reduced pH. At high FFA/albumin ratios (5 or above) lipolysis was similar at normal and reduced pH. The antilipolytic effect of decreased pH was equally pronounced in perifused fat cells, where inhibitory substances are not allowed to accumulate. Our results suggest that the antilipolytic effect of acidosis is mainly a direct effect of the increase in H+ ion concentration. The inhibitory effect of acidosis on various responses to beta-adrenoceptor stimulation may be caused by a decreased formation of cyclic AMP in turn caused directly by the decrease in pH."}
{"id": "PMID:22989", "title": "Psychic dependence? A different formulation of the problem with a view to the reorientation of therapy for chronic drug addiction.", "content": "Disputing the concept of \"psychic dependence\", the authors review six motivations to use addictive drugs, four of which pertain to the moment of assumption of the habit, and two of which, identifiable with physical and psychic dependence, depend on breaking of the habit. While physical dependence is linked to withdrawal syndrome, psychic dependence, in the authors' opinion, is related to a longstanding previous state of true of masked endogenous depression (in this case it would be well termed \"neuropsychological dependence\"), and the drug taking is only a maladaptive self-medication. This thesis is substantiated by the literature reporting, in chronic drug addicts, the use of the whole series of antidepressants (i.e. tricyclics, doxepine, lithium, etc.) with noticeable therapeutical success. In accordance with other reports and with personal experience, the authors assign great importance to the drugs acting, directly or indirectly, on GABA, i.e. L-glutamine, piracetam, and, particularly, N-dipropylacetic acid.", "contents": "Psychic dependence? A different formulation of the problem with a view to the reorientation of therapy for chronic drug addiction. Disputing the concept of \"psychic dependence\", the authors review six motivations to use addictive drugs, four of which pertain to the moment of assumption of the habit, and two of which, identifiable with physical and psychic dependence, depend on breaking of the habit. While physical dependence is linked to withdrawal syndrome, psychic dependence, in the authors' opinion, is related to a longstanding previous state of true of masked endogenous depression (in this case it would be well termed \"neuropsychological dependence\"), and the drug taking is only a maladaptive self-medication. This thesis is substantiated by the literature reporting, in chronic drug addicts, the use of the whole series of antidepressants (i.e. tricyclics, doxepine, lithium, etc.) with noticeable therapeutical success. In accordance with other reports and with personal experience, the authors assign great importance to the drugs acting, directly or indirectly, on GABA, i.e. L-glutamine, piracetam, and, particularly, N-dipropylacetic acid."}
{"id": "PMID:22990", "title": "A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.", "content": "Repeated doses of 5 mg nitrazepam, 15 mg flurazepam, and 1 mg flunitrazepam improved subjective assessments of the ease of getting to sleep and the perceived quality of induced sleep in a population of 30 healthy volunteers. The subjective reports of improved sleep inducement were related to a perceived difficulty in awakening from sleep the morning following medication. This subjectively reported \"hangover\" is also shown in the impairment of mental arithmetic abilities as measured on the serial subtraction of sevens technique. However, complex psychomotor performance is unaffected by repeated administration of these three benzodiazepine derivatives, although these later results are somewhat equivocal. Evidence of a \"rebound phenomenon\" following 4 nights' withdrawal of active medication is shown in both subjective and objective measures of sleep and early morning behaviour.", "contents": "A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication. Repeated doses of 5 mg nitrazepam, 15 mg flurazepam, and 1 mg flunitrazepam improved subjective assessments of the ease of getting to sleep and the perceived quality of induced sleep in a population of 30 healthy volunteers. The subjective reports of improved sleep inducement were related to a perceived difficulty in awakening from sleep the morning following medication. This subjectively reported \"hangover\" is also shown in the impairment of mental arithmetic abilities as measured on the serial subtraction of sevens technique. However, complex psychomotor performance is unaffected by repeated administration of these three benzodiazepine derivatives, although these later results are somewhat equivocal. Evidence of a \"rebound phenomenon\" following 4 nights' withdrawal of active medication is shown in both subjective and objective measures of sleep and early morning behaviour."}
{"id": "PMID:22991", "title": "Effects of clomiphene citrate administraiton on the hypothalamo-pituitary-gonadal axis of male chronic schizophrenics.", "content": "The clomiphene citrate stimulation test was performed in 16 adult male chronic hebephrenic schizophrenics (10 off therapy from 3 months to 1 year and six on therapy with phenothiazines or haloperidol) and in five normal controls, matched for age. Clomiphene citrate was given orally at a daily dose of 150 mg, divided into three doses, for 8 days. FSH, LH and testosterone levels were assayed before the administration of clomiphene citrate and after 4 and 8 days of treatment. Schizophrenics showed normal increase of FSH levels during the clomiphene administration, while LH and testosterone responses were blunted. Phenothiazines or haloperiodol had no effect on the test.", "contents": "Effects of clomiphene citrate administraiton on the hypothalamo-pituitary-gonadal axis of male chronic schizophrenics. The clomiphene citrate stimulation test was performed in 16 adult male chronic hebephrenic schizophrenics (10 off therapy from 3 months to 1 year and six on therapy with phenothiazines or haloperidol) and in five normal controls, matched for age. Clomiphene citrate was given orally at a daily dose of 150 mg, divided into three doses, for 8 days. FSH, LH and testosterone levels were assayed before the administration of clomiphene citrate and after 4 and 8 days of treatment. Schizophrenics showed normal increase of FSH levels during the clomiphene administration, while LH and testosterone responses were blunted. Phenothiazines or haloperiodol had no effect on the test."}
{"id": "PMID:22985", "title": "Substance P-like peptides and vasopressin release from posterior pituitary lobe incubated in situ after intracarotid injections of hypertonic solution in rats.", "content": "The experiments were performed on male rats, drinking 2% NaCl solution ad libitum for 12 days instead of tap water. The pituitary gland was exposed by the transpharyngeal approach under urethane-chloralose anaesthesia. The posterior lobe remained in neural and partial vascular connection with the hypothalamus, whereas the anterior lobe was entirely removed. Samples of the outflow medium from the incubated in situ rat posterior pituitary lobe were collected during 30 min intervals. Substance P-like peptides and vasopressin activities were assayed by the biological tests. Injections of hypertonic solution into the internal carotid artery did not change vasopressin release, but induced an increase in Substance P release from the posterior pituitary lobe into the incubation medium. Under conditions of unexcitability of the osmosensitive cells, triggering vasopressin release, the injection of hypertonic solution into the internal carotid artery stimulated the Substance P-like peptides release from the posterior pituitary lobe.", "contents": "Substance P-like peptides and vasopressin release from posterior pituitary lobe incubated in situ after intracarotid injections of hypertonic solution in rats. The experiments were performed on male rats, drinking 2% NaCl solution ad libitum for 12 days instead of tap water. The pituitary gland was exposed by the transpharyngeal approach under urethane-chloralose anaesthesia. The posterior lobe remained in neural and partial vascular connection with the hypothalamus, whereas the anterior lobe was entirely removed. Samples of the outflow medium from the incubated in situ rat posterior pituitary lobe were collected during 30 min intervals. Substance P-like peptides and vasopressin activities were assayed by the biological tests. Injections of hypertonic solution into the internal carotid artery did not change vasopressin release, but induced an increase in Substance P release from the posterior pituitary lobe into the incubation medium. Under conditions of unexcitability of the osmosensitive cells, triggering vasopressin release, the injection of hypertonic solution into the internal carotid artery stimulated the Substance P-like peptides release from the posterior pituitary lobe."}
{"id": "PMID:22993", "title": "Neuronal aspects of opiate dependence and tolerance in comparison to central depressants.", "content": "Some acute and chronic effects of opiates and of central depressants have been reviewed, in order that a comparison can be made between the actions of these drugs. Special emphasis has been given to opiate-induced changes at the neuronal level, which have been studied either by the direct microelectrophoretic application of drugs to single neurones or by application of drugs to the myenteric plexus/longitudinal muscle preparation of the guinea pig ileum. Available evidence suggests that chronic exposure of nervous tissue to opiates as well as to central depressants causes changes in neuronal excitability, which become apparent upon withdrawal of the drug. Although opiates and central depressants cause similar changes they appear to do so by different mechanisms. Such differences between the mode of action of opiates and central depressants may provide an explanation for the differing chronic effects of these drugs.", "contents": "Neuronal aspects of opiate dependence and tolerance in comparison to central depressants. Some acute and chronic effects of opiates and of central depressants have been reviewed, in order that a comparison can be made between the actions of these drugs. Special emphasis has been given to opiate-induced changes at the neuronal level, which have been studied either by the direct microelectrophoretic application of drugs to single neurones or by application of drugs to the myenteric plexus/longitudinal muscle preparation of the guinea pig ileum. Available evidence suggests that chronic exposure of nervous tissue to opiates as well as to central depressants causes changes in neuronal excitability, which become apparent upon withdrawal of the drug. Although opiates and central depressants cause similar changes they appear to do so by different mechanisms. Such differences between the mode of action of opiates and central depressants may provide an explanation for the differing chronic effects of these drugs."}
{"id": "PMID:22986", "title": "Effect of pH and lactate on glucose uptake by red and white skeletal muscle in vitro.", "content": "The diaphragm muscle (the red muscle) and m. obliquus externus abdominis (the white muscle) were incubated in phosphate buffer at pH 7.4 and 6.8 in the presence of different concentrations of sodium lactate (0, 5, 10 and 30 mM). None of the used lactate concentrations changed significantly glucose uptake by the both muscles at pH 7.4.  At pH 6.8 lactate in a concentration of 30 mM decreased significantly glucose uptake by the white muscle. At pH 7.4 glucose uptake by the white muscle was significantly lower than that by the red one in the presence of 10 and 30 mM of sodium lactate while at pH 6.8 in the absence of lactate and in the presence of 5 and 30 mM of lactate. Acidosis affected in smaller degree glucose uptake by the red muscle than by the white one. It may be supposed that the impairement of glucose uptake by acidosis and lactic acid in strenously working skeletal muscles can limit the amount of energy sources available for the muscles. Subsequently, it may be one of the factors limiting the ability of the muscles to continue the exhausting exercise.", "contents": "Effect of pH and lactate on glucose uptake by red and white skeletal muscle in vitro. The diaphragm muscle (the red muscle) and m. obliquus externus abdominis (the white muscle) were incubated in phosphate buffer at pH 7.4 and 6.8 in the presence of different concentrations of sodium lactate (0, 5, 10 and 30 mM). None of the used lactate concentrations changed significantly glucose uptake by the both muscles at pH 7.4.  At pH 6.8 lactate in a concentration of 30 mM decreased significantly glucose uptake by the white muscle. At pH 7.4 glucose uptake by the white muscle was significantly lower than that by the red one in the presence of 10 and 30 mM of sodium lactate while at pH 6.8 in the absence of lactate and in the presence of 5 and 30 mM of lactate. Acidosis affected in smaller degree glucose uptake by the red muscle than by the white one. It may be supposed that the impairement of glucose uptake by acidosis and lactic acid in strenously working skeletal muscles can limit the amount of energy sources available for the muscles. Subsequently, it may be one of the factors limiting the ability of the muscles to continue the exhausting exercise."}
{"id": "PMID:22994", "title": "The first cleavage site in pepsinogen activation.", "content": "By incubation of porcine, bovine, canine, or chicken pepsinogens and calf prochymosin with pepstatin at pH 2.5, the first active protein generated on activation is trapped in an inactive complex. The first activation peptide liberated from porcine pepsinogen has been identified as residues 1-16 whereas that from prochymosin is derived from residues 1-27. This suggests that pepsin and chymosin are not formed by one-step conversions from their zymogens, but by (different) sequential, activation mechanisms.", "contents": "The first cleavage site in pepsinogen activation. By incubation of porcine, bovine, canine, or chicken pepsinogens and calf prochymosin with pepstatin at pH 2.5, the first active protein generated on activation is trapped in an inactive complex. The first activation peptide liberated from porcine pepsinogen has been identified as residues 1-16 whereas that from prochymosin is derived from residues 1-27. This suggests that pepsin and chymosin are not formed by one-step conversions from their zymogens, but by (different) sequential, activation mechanisms."}
{"id": "PMID:22995", "title": "Inactive renin--a renin proenzyme?", "content": "Human plasma contains an inactive form of renin with a m.w. of 55,000, as against around 40,000 for active human renin. After acidification to pH 3.0 or incubation with trypsin, the inactive renin becomes more active and the molecular weight falls to that of active renin. In human kidney extracts, an increase in renin concentration also occurred after acidification. The inactive form of renin may be similar to that of rabbit kidneys, which contain an inactive renin that can be activated by removal of an acid-labile inhibitor. The question as to whether the inactive material is a renin proenzyme is discussed.", "contents": "Inactive renin--a renin proenzyme? Human plasma contains an inactive form of renin with a m.w. of 55,000, as against around 40,000 for active human renin. After acidification to pH 3.0 or incubation with trypsin, the inactive renin becomes more active and the molecular weight falls to that of active renin. In human kidney extracts, an increase in renin concentration also occurred after acidification. The inactive form of renin may be similar to that of rabbit kidneys, which contain an inactive renin that can be activated by removal of an acid-labile inhibitor. The question as to whether the inactive material is a renin proenzyme is discussed."}
{"id": "PMID:22996", "title": "Characteristics and functions of proteinase A and its inhibitors in yeast.", "content": "A purification and some properties of proteinase A from yeast are described. A specific macromolecular inhibitor of proteinase A from yeast cytosol has been isolated and shown to be a protein (molecular weight 7,700) consisting of a majority of polar amino acids. Proline, arginine, cysteine and tryptophan were not detected in the inhibitor. Possible biological functions of proteinase A and the proteinase A-inhibitor (and of other yeast proteinases and their inhibitors) in the following processes are discussed: general protein turnover, catabolite inactivation of enzymes, enzyme degradation at starvation and at transition to spore formation, and activation of pre-enzymes and precursor proteins by limited proteolysis.", "contents": "Characteristics and functions of proteinase A and its inhibitors in yeast. A purification and some properties of proteinase A from yeast are described. A specific macromolecular inhibitor of proteinase A from yeast cytosol has been isolated and shown to be a protein (molecular weight 7,700) consisting of a majority of polar amino acids. Proline, arginine, cysteine and tryptophan were not detected in the inhibitor. Possible biological functions of proteinase A and the proteinase A-inhibitor (and of other yeast proteinases and their inhibitors) in the following processes are discussed: general protein turnover, catabolite inactivation of enzymes, enzyme degradation at starvation and at transition to spore formation, and activation of pre-enzymes and precursor proteins by limited proteolysis."}
{"id": "PMID:22997", "title": "Comparison of the primary structures of acidic proteinases and of their zymogens.", "content": "From the scattered information about primary structures of aspartate proteinases the following general features appear: 1) Sequence determinations show that two catalytically active aspartic acid residues are located in highly conservative surroundings. 2) Zymogens have so far only been found for extracellular aspartate proteinases of the vertebrates. The zymogens from the gastric mucosa are converted into active enzymes by a limited proteolysis releasing 42 to 44 residues from the NH2-terminus. A common pattern of basic and apolar residues is observed in this NH2-terminal segment. 3) In the presently known structures gastric proteinases and their zymogens have about 40% of all residues in common. The sequence of penicillopepsin shows 18% of identity with the gastric proteinases.", "contents": "Comparison of the primary structures of acidic proteinases and of their zymogens. From the scattered information about primary structures of aspartate proteinases the following general features appear: 1) Sequence determinations show that two catalytically active aspartic acid residues are located in highly conservative surroundings. 2) Zymogens have so far only been found for extracellular aspartate proteinases of the vertebrates. The zymogens from the gastric mucosa are converted into active enzymes by a limited proteolysis releasing 42 to 44 residues from the NH2-terminus. A common pattern of basic and apolar residues is observed in this NH2-terminal segment. 3) In the presently known structures gastric proteinases and their zymogens have about 40% of all residues in common. The sequence of penicillopepsin shows 18% of identity with the gastric proteinases."}
{"id": "PMID:22998", "title": "Acid protease and its proenzyme from human seminal plasma.", "content": "An acid protease, with an optimum pH of 2.5, exists in seminal plasma in a proenzyme form. In acidic pH, the proenzyme is converted into the active form, resulting in the release of small molecular weight peptide. The extent and rate of proenzyme-active enzyme conversion is absolutely dependent on pH. Between pH 5 and 2, as the pH is lowered, the extent of conversion increases and reaches a maximum between pH 3 and 2. The kinetics of activation shift from first-order between pH 2 and 4 to more complexity with a lag period between pH 4.5 and 5. Under physiological conditions, the proenzyme might be activated by coming into contact with acidic vaginal fluid during ejaculation. The acid protease can hydrolyze the cervical mucus protein.", "contents": "Acid protease and its proenzyme from human seminal plasma. An acid protease, with an optimum pH of 2.5, exists in seminal plasma in a proenzyme form. In acidic pH, the proenzyme is converted into the active form, resulting in the release of small molecular weight peptide. The extent and rate of proenzyme-active enzyme conversion is absolutely dependent on pH. Between pH 5 and 2, as the pH is lowered, the extent of conversion increases and reaches a maximum between pH 3 and 2. The kinetics of activation shift from first-order between pH 2 and 4 to more complexity with a lag period between pH 4.5 and 5. Under physiological conditions, the proenzyme might be activated by coming into contact with acidic vaginal fluid during ejaculation. The acid protease can hydrolyze the cervical mucus protein."}
{"id": "PMID:22999", "title": "Intramolecular activation of pepsinogen.", "content": "Two pathways for pepsinogen activation have been demonstrated. Intramolecular activation, which is kinetically first-order, predominates over the autocatalytic pathway if the pH is below 3 and the protein concentration is less than 1 mg/ml during activation. Intramolecular pepsinogen activation is inhibited either by pepstatin, a potent pepsin inhibitor, or by purified globin from hemoglobin, a good pepsin substrate. Also, pepsinogen at pH 2 can be bound to a pepstatin-Sepharose column and recovered as native zymogen upon elution in pH 8 buffer. Kinetic studies of the globin inhibition of pepsinogen activation show that globin binds to a pepsinogen intermediate. This interaction gives rise to competitive inhibition of intramolecular pepsinogen activation. The evidence presented in this paper suggests that pepsinogen is converted rapidly upon acidification to the pepsinogen intermediate delta.", "contents": "Intramolecular activation of pepsinogen. Two pathways for pepsinogen activation have been demonstrated. Intramolecular activation, which is kinetically first-order, predominates over the autocatalytic pathway if the pH is below 3 and the protein concentration is less than 1 mg/ml during activation. Intramolecular pepsinogen activation is inhibited either by pepstatin, a potent pepsin inhibitor, or by purified globin from hemoglobin, a good pepsin substrate. Also, pepsinogen at pH 2 can be bound to a pepstatin-Sepharose column and recovered as native zymogen upon elution in pH 8 buffer. Kinetic studies of the globin inhibition of pepsinogen activation show that globin binds to a pepsinogen intermediate. This interaction gives rise to competitive inhibition of intramolecular pepsinogen activation. The evidence presented in this paper suggests that pepsinogen is converted rapidly upon acidification to the pepsinogen intermediate delta."}
{"id": "PMID:23001", "title": "A cat head model with isolated perfusion by the animal's own blood.", "content": "A model consisting of a cat head perfused in isolation with the animal's own blood is described. The use of endogenous blood allows the organ to function under physiological conditions for several hours. The blood is taken from the abdominal aorta of the anaesthetized animal and passed to the carotid arteries via an extracorporeal circulation system. The perfusion pressure can be varied at will and is regulated electronically. The volume of blood in the extracorporeal circulation system is only 6 ml. The tests performed on this model were designed to study the behaviour of the cortical EEG and the cortical micro flow. Neither of these parameters underwent any change after institution of the artificial perfusion, and the blood gases also remained fairly stable. The model is suitable for studying both physiological and pharmacological problems.", "contents": "A cat head model with isolated perfusion by the animal's own blood. A model consisting of a cat head perfused in isolation with the animal's own blood is described. The use of endogenous blood allows the organ to function under physiological conditions for several hours. The blood is taken from the abdominal aorta of the anaesthetized animal and passed to the carotid arteries via an extracorporeal circulation system. The perfusion pressure can be varied at will and is regulated electronically. The volume of blood in the extracorporeal circulation system is only 6 ml. The tests performed on this model were designed to study the behaviour of the cortical EEG and the cortical micro flow. Neither of these parameters underwent any change after institution of the artificial perfusion, and the blood gases also remained fairly stable. The model is suitable for studying both physiological and pharmacological problems."}
{"id": "PMID:23003", "title": "An in vitro method for predicting the bioavailability of iron from foods.", "content": "An in vitro method for the determination of availability of nonheme iron from foods and diets was investigated. Food was extracted with pepsin-HCl at pH 1.35 and subsequently the pH was adjusted to pH 7.5 and filtered. Ionizable iron was determined in the pH 7.5 filterate by the alpha, alpha-dipyridyl method. The percent iron absorption from the same diets observed in the adult males. Ionizable iron at pH 7.5 was shown to increase in presence of ascorbic acid and meat extract while it decreased in presence of phytate and tannins, similar to the effects of these factors on iron absorption in human subjects. Based on these observations it is proposed that ionizable iron at pH 7.5 determined as described in this study can be used as a reliable measure of bioavailability of nonheme iron in foods.", "contents": "An in vitro method for predicting the bioavailability of iron from foods. An in vitro method for the determination of availability of nonheme iron from foods and diets was investigated. Food was extracted with pepsin-HCl at pH 1.35 and subsequently the pH was adjusted to pH 7.5 and filtered. Ionizable iron was determined in the pH 7.5 filterate by the alpha, alpha-dipyridyl method. The percent iron absorption from the same diets observed in the adult males. Ionizable iron at pH 7.5 was shown to increase in presence of ascorbic acid and meat extract while it decreased in presence of phytate and tannins, similar to the effects of these factors on iron absorption in human subjects. Based on these observations it is proposed that ionizable iron at pH 7.5 determined as described in this study can be used as a reliable measure of bioavailability of nonheme iron in foods."}
{"id": "PMID:23004", "title": "Effect of pentagastrin infusion on gastric emptying rate of solid food in man.", "content": "The effect of intravenous pentagrastin (4 microgram/kg-hr) on the rate of gastric emptying of solid food was studied in 6 normal men. A mean consisting of one 99mTc-tagged chicken liver mixed with beef stew and taken with 200 ml of water was followed on its passage through the gastrointestinal tract by intermittent scanning with a gamma camera. The rate of the linear gastric emptying pattern was slowed by pentagastrin in every individual. The pH and titratable acidity of the gastric contents were similar in the pentagastrin and the control infusions. Neutralization of the gastric contents with bicarbonate in the pentagastrin studies did not alter gastric emptying rates. The results indicate that pentagastrin slows gastric emptying of solid food in man by an effect apart from acid secretion. The myoelectrical correlates of such an observation are uncertain.", "contents": "Effect of pentagastrin infusion on gastric emptying rate of solid food in man. The effect of intravenous pentagrastin (4 microgram/kg-hr) on the rate of gastric emptying of solid food was studied in 6 normal men. A mean consisting of one 99mTc-tagged chicken liver mixed with beef stew and taken with 200 ml of water was followed on its passage through the gastrointestinal tract by intermittent scanning with a gamma camera. The rate of the linear gastric emptying pattern was slowed by pentagastrin in every individual. The pH and titratable acidity of the gastric contents were similar in the pentagastrin and the control infusions. Neutralization of the gastric contents with bicarbonate in the pentagastrin studies did not alter gastric emptying rates. The results indicate that pentagastrin slows gastric emptying of solid food in man by an effect apart from acid secretion. The myoelectrical correlates of such an observation are uncertain."}
{"id": "PMID:23005", "title": "PH-dependent drug release from certain commercial tablets.", "content": "A dissolution-dialysis profile for each of several brands of nitrofurantoin, hydrochlorothiazide and sulfisoxazole tablets was developed at three pH levels. The study used a two-compartment diffusion cell with a semipermeable cellophane membrane. Nitrofuratoin tablets were tested at pH values of 7.2, 4.7 and 1.2; sulfisoxazole tablets at 7.2, 5.5 and less than 1. Studies with hydrochlorothiazide tablets were terminated because the pH of the dissolution medium had no effect of practical significance on dissolution or dialysis rates. The dissolution rates of the nitrofurantoin and sulfisoxazole tablets were highly brand-individualized and complex. The effects of pH upon a particular formulation were unpredictable. The results suggest that dissolution testing at one fixed pH, as commonly practiced, may be insufficient for some products. This pH-dependent release characteristic may not correspond to a change in bioavailability in all cases, but it represents a potential problem which should be considered by the formulator.", "contents": "PH-dependent drug release from certain commercial tablets. A dissolution-dialysis profile for each of several brands of nitrofurantoin, hydrochlorothiazide and sulfisoxazole tablets was developed at three pH levels. The study used a two-compartment diffusion cell with a semipermeable cellophane membrane. Nitrofuratoin tablets were tested at pH values of 7.2, 4.7 and 1.2; sulfisoxazole tablets at 7.2, 5.5 and less than 1. Studies with hydrochlorothiazide tablets were terminated because the pH of the dissolution medium had no effect of practical significance on dissolution or dialysis rates. The dissolution rates of the nitrofurantoin and sulfisoxazole tablets were highly brand-individualized and complex. The effects of pH upon a particular formulation were unpredictable. The results suggest that dissolution testing at one fixed pH, as commonly practiced, may be insufficient for some products. This pH-dependent release characteristic may not correspond to a change in bioavailability in all cases, but it represents a potential problem which should be considered by the formulator."}
{"id": "PMID:23007", "title": "Metabolic effects of constant hypertonic glucose infusion in well-oxygenated fetuses.", "content": "In order to investigate the metabolic effects of a constant hypertonic glucose infusion in well-oxygenated fetuses, ten experiments were carried out in nine long-term experiments in fetal lambs. It appeared that a constant hypertonic glucose infusion did not significantly affect the fetal blood gases, pH, and plasma lactate levels when fetal glucose was kept below 150 mg. per 100 ml. It was also demonstrated that glucose infusions significantly increased the fetal lactate levels and decreased the blood pH when fetal plasma glucose was over 150 mg. per 100 ml. However, there was no decrease in fetal PO2 and pco2 until fetal glucose reached values over 300 mg. per 100 ml. These studies suggest that constant hypertonic glucose infusion does not improve fetal blood gases or pH and that fetal hyperglycemia over 300 mg. per 100 ml. produces severe metabolic acidosis.", "contents": "Metabolic effects of constant hypertonic glucose infusion in well-oxygenated fetuses. In order to investigate the metabolic effects of a constant hypertonic glucose infusion in well-oxygenated fetuses, ten experiments were carried out in nine long-term experiments in fetal lambs. It appeared that a constant hypertonic glucose infusion did not significantly affect the fetal blood gases, pH, and plasma lactate levels when fetal glucose was kept below 150 mg. per 100 ml. It was also demonstrated that glucose infusions significantly increased the fetal lactate levels and decreased the blood pH when fetal plasma glucose was over 150 mg. per 100 ml. However, there was no decrease in fetal PO2 and pco2 until fetal glucose reached values over 300 mg. per 100 ml. These studies suggest that constant hypertonic glucose infusion does not improve fetal blood gases or pH and that fetal hyperglycemia over 300 mg. per 100 ml. produces severe metabolic acidosis."}
{"id": "PMID:23008", "title": "The skin biopsy in the diagnosis of acute graft-versus-host disease in man.", "content": "Criteria for diagnosis of acute graft-versus-host disease (GVHD) using skin biopsies were derived from a) general experience with more than 300 human marrow grafts and b) the results of \"blind\" studies of skin biopsy specimens of patients grafted with either allogeneic or syngeneic marrow. Large doses of cytotoxic drugs and irradiation given before grafting can produce transient skin changes interfering significantly with the diagnosis of GVHD. Artifacts can also cause difficulty. Epidermal cytologic atypia, dyskeratosis, and satellitosis were present both in allografted patients with acute clinical GVHD of multiple systems and in patients given autologous or syngeneic marrow. Due to the marked overlap in histopathologic findings between these two types of skin injury, frequent serial skin biopsies must be combined with all other available clinical and biopsy data to provide reliable diagnosis of acute GVHD in man.", "contents": "The skin biopsy in the diagnosis of acute graft-versus-host disease in man. Criteria for diagnosis of acute graft-versus-host disease (GVHD) using skin biopsies were derived from a) general experience with more than 300 human marrow grafts and b) the results of \"blind\" studies of skin biopsy specimens of patients grafted with either allogeneic or syngeneic marrow. Large doses of cytotoxic drugs and irradiation given before grafting can produce transient skin changes interfering significantly with the diagnosis of GVHD. Artifacts can also cause difficulty. Epidermal cytologic atypia, dyskeratosis, and satellitosis were present both in allografted patients with acute clinical GVHD of multiple systems and in patients given autologous or syngeneic marrow. Due to the marked overlap in histopathologic findings between these two types of skin injury, frequent serial skin biopsies must be combined with all other available clinical and biopsy data to provide reliable diagnosis of acute GVHD in man."}
{"id": "PMID:23010", "title": "Cytoplasmic dipeptidase activities of kidney, ileum, jejunum, liver, muscle, and blood.", "content": "Peptide hydrolase activities against glycyl-L-leucine and glycylglycine were investigated in the soluble fractions of blood, liver, kidney cortex, skeletal muscle (gastrocnemius), and jejunal and ileal mucosa of rats. The maximal hydrolase activity in each tissue was determined when the incubation conditions, such as time, pH, substrate and enzyme concentrations, and ionic requirements were optimal. The kinetic constants (apparent Km and Vmax) were determined from Lineweaver-Burk double reciprocal graphs. Maximal hydrolysis rates against both dipeptides were many times greater by kidney and intestinal segments than by those of muscle, liver, or blood. The order of Vmax for hydrolase activity against glycylleucine was kidney greater than ileum greater than jejunum greater than liver greater than muscle greater than blood, and the order against glycylglycine was ileum greater than kidney greater than jejunum greater than liver greater than muscle. Those tissues that had the lowest Vmax values (liver and muscle), when calculated on the basis of tissue weights, were shown to have activities comparable to the others. Results of this study are consistent with our previous findings that: 1) glycylleucine half-life in plasma is shorter than that of glycylglycine, and 2) disappearance rates of these dipeptides from plasma are not affected by nephrectomy or enterectomy.", "contents": "Cytoplasmic dipeptidase activities of kidney, ileum, jejunum, liver, muscle, and blood. Peptide hydrolase activities against glycyl-L-leucine and glycylglycine were investigated in the soluble fractions of blood, liver, kidney cortex, skeletal muscle (gastrocnemius), and jejunal and ileal mucosa of rats. The maximal hydrolase activity in each tissue was determined when the incubation conditions, such as time, pH, substrate and enzyme concentrations, and ionic requirements were optimal. The kinetic constants (apparent Km and Vmax) were determined from Lineweaver-Burk double reciprocal graphs. Maximal hydrolysis rates against both dipeptides were many times greater by kidney and intestinal segments than by those of muscle, liver, or blood. The order of Vmax for hydrolase activity against glycylleucine was kidney greater than ileum greater than jejunum greater than liver greater than muscle greater than blood, and the order against glycylglycine was ileum greater than kidney greater than jejunum greater than liver greater than muscle. Those tissues that had the lowest Vmax values (liver and muscle), when calculated on the basis of tissue weights, were shown to have activities comparable to the others. Results of this study are consistent with our previous findings that: 1) glycylleucine half-life in plasma is shorter than that of glycylglycine, and 2) disappearance rates of these dipeptides from plasma are not affected by nephrectomy or enterectomy."}
{"id": "PMID:23012", "title": "Transport of H+ against electrochemical gradients in turtle urinary bladder.", "content": "Active H+ transport (JH) by the isolated turtle bladder was inhibited by either an applied chemical gradient (deltapH) or an electrical gradient (deltapsi). The relation of JH to either deltapH or deltapsi was linear, and the slopes and the force gradients required to bring JH to zero were similar with both methods. The transport system was analyzed in terms of an equivalent circuit model comprising a proton motive force (PMF), an active conductance (LH) in series with the pump, and a parallel or passive conductance which may be ignored in this preparation. Increasing ambient PCO2 markedly increased JH and the active conductance (as deltaJH/deltadeltapH) but had no effect on the apparent PMF (PMF'). Similarly, acetazolamide caused comparable decreases in JH and LH without change in PMF'. Inhibition of metabolism by deoxygenation, deoxy-D-glucose, or depletion of metabolic substrate caused large decreases in JH and LH with reduction in PMF' of less than 14%. Glucose addition increased JH and LH but caused a slight decrease in PMF'. Thus, the experimental maneuvers affected the transport rate primarily through changes in the active conductance. Since PMF' was little affected, the force of the pump must be determined by factors other than the metabolic driving reaction alone. Conductance factors relating to transport as well as to metabolism participate in controlling PMF.", "contents": "Transport of H+ against electrochemical gradients in turtle urinary bladder. Active H+ transport (JH) by the isolated turtle bladder was inhibited by either an applied chemical gradient (deltapH) or an electrical gradient (deltapsi). The relation of JH to either deltapH or deltapsi was linear, and the slopes and the force gradients required to bring JH to zero were similar with both methods. The transport system was analyzed in terms of an equivalent circuit model comprising a proton motive force (PMF), an active conductance (LH) in series with the pump, and a parallel or passive conductance which may be ignored in this preparation. Increasing ambient PCO2 markedly increased JH and the active conductance (as deltaJH/deltadeltapH) but had no effect on the apparent PMF (PMF'). Similarly, acetazolamide caused comparable decreases in JH and LH without change in PMF'. Inhibition of metabolism by deoxygenation, deoxy-D-glucose, or depletion of metabolic substrate caused large decreases in JH and LH with reduction in PMF' of less than 14%. Glucose addition increased JH and LH but caused a slight decrease in PMF'. Thus, the experimental maneuvers affected the transport rate primarily through changes in the active conductance. Since PMF' was little affected, the force of the pump must be determined by factors other than the metabolic driving reaction alone. Conductance factors relating to transport as well as to metabolism participate in controlling PMF."}
{"id": "PMID:23014", "title": "Hydrogen ion metabolism.", "content": "The renal and respiratory systems regulate acid base homeostasis by modifying the bicarbonate buffer pair HCO3- and CO2; other buffer systems adjust to alterations in this pair. The pH change following addition of metabolic acid, or base, is modified initially by the body's buffers. Subsequent respiratory compensation, by retention or excretion of CO2, modifies further this change before renal corrective responses finally occur. A primary respiratory acid base change is modified initially by cellular buffers, with renal compensatory mechanisms adjusting slowly to this change. However correction of the respiratory pH disorder only occurs with correction of the primary disease process. The body's capacity, therefore, to adjust to a matabolic acid base defect, appears greater than that observed with a primary respiratory pH abnormality. Treatment in all acid base disorders focuses initially upon the primary diseases process; thereafter therapeutic manipulation of the HCO3-, CO2 buffer pair, to aid the body's compensatory processes, can be considered.", "contents": "Hydrogen ion metabolism. The renal and respiratory systems regulate acid base homeostasis by modifying the bicarbonate buffer pair HCO3- and CO2; other buffer systems adjust to alterations in this pair. The pH change following addition of metabolic acid, or base, is modified initially by the body's buffers. Subsequent respiratory compensation, by retention or excretion of CO2, modifies further this change before renal corrective responses finally occur. A primary respiratory acid base change is modified initially by cellular buffers, with renal compensatory mechanisms adjusting slowly to this change. However correction of the respiratory pH disorder only occurs with correction of the primary disease process. The body's capacity, therefore, to adjust to a matabolic acid base defect, appears greater than that observed with a primary respiratory pH abnormality. Treatment in all acid base disorders focuses initially upon the primary diseases process; thereafter therapeutic manipulation of the HCO3-, CO2 buffer pair, to aid the body's compensatory processes, can be considered."}
{"id": "PMID:23013", "title": "Specific drug interactions in anaesthesia.", "content": "The sites and mechanisms of the interaction of drugs have been discussed with special relevance to the work of the anaesthetist.", "contents": "Specific drug interactions in anaesthesia. The sites and mechanisms of the interaction of drugs have been discussed with special relevance to the work of the anaesthetist."}
{"id": "PMID:23018", "title": "[Flunitrazepam, trazodone and sulpiride in the treatment of recovery reactions after ketamine anesthesia].", "content": "The authors studied the effects of flunitrazepam, trazodone and sulpiride on recovery reactions following ketamine anaesthesia, in male patients aged between 15 and 25 years, following minor orthopaedic surgery. Only flunitrazepam and trazodone proved to be effective, whilst sulpiride was quite useless in the prevention of recovery reactions. The authors nevertheless feel that trazodone is preferable to flunitrazepam since it reduces all recovery reactions and, in particular, because it reduces the agitation induced by ketamine, rendering the pseudo-hallucinations pleasant, and because it is free of the hypnotic component of flunitrazepam, often inconstant and sometimes responsible for the patient swallowing his tongue.", "contents": "[Flunitrazepam, trazodone and sulpiride in the treatment of recovery reactions after ketamine anesthesia]. The authors studied the effects of flunitrazepam, trazodone and sulpiride on recovery reactions following ketamine anaesthesia, in male patients aged between 15 and 25 years, following minor orthopaedic surgery. Only flunitrazepam and trazodone proved to be effective, whilst sulpiride was quite useless in the prevention of recovery reactions. The authors nevertheless feel that trazodone is preferable to flunitrazepam since it reduces all recovery reactions and, in particular, because it reduces the agitation induced by ketamine, rendering the pseudo-hallucinations pleasant, and because it is free of the hypnotic component of flunitrazepam, often inconstant and sometimes responsible for the patient swallowing his tongue."}
{"id": "PMID:23019", "title": "[Changes in the affinity of oxygen for hemoglobin during general anesthesia].", "content": "The well known effects of the lowering of the intraerythrocyte 2, 3, diphosphoglycerate (2, 3, DPG) level and hypothermia, on the affinity of oxygen for hemoglobin, lead the authors to study the influence of these parameters on this affinity during general anesthesia. The following observations were made in 15 adult subjects, undergoing prolonged general anaesthesia (average time: 3 hrs. 10 minutes): the dissociation curve of oxyhemoglobin (DCO) by the method of mixing, the intraerythrocyte 2,3, DPG level, the hemoglobin concentration and arterial blood parameters (PO2, PCO2, pH). These measurements were recorded before and after the general anaesthesia. The results were the following: a significant reduction of P50, measured under standard conditions (from 27.64 +/- 1.74 torr to 25.57 +/- 2.28, p less than or equal to 0.01) associated with a decrease in 2,3, DPG (from 0.94 +/- 0.31 mol/mol Hb at 0.64 +/- 0.24 p less than 0.01). Among the factors responsible for this variation in the affinity, it was proved that the volume of blood transfused was of importance as well as a decrease in body temperature during the operation. When the temperature is made to vary from 37 degrees C to 35 degrees C. the P50 ranges from 25.57 +/- 2.28 to 22.86 +/- 0.97 (p less than 0.01). To conclude the authors underline the importance of hypothermia and the volume of blood transfused (average time of preservation = 15 days) on the effects of the affinity of oxygen for hemoglobin.", "contents": "[Changes in the affinity of oxygen for hemoglobin during general anesthesia]. The well known effects of the lowering of the intraerythrocyte 2, 3, diphosphoglycerate (2, 3, DPG) level and hypothermia, on the affinity of oxygen for hemoglobin, lead the authors to study the influence of these parameters on this affinity during general anesthesia. The following observations were made in 15 adult subjects, undergoing prolonged general anaesthesia (average time: 3 hrs. 10 minutes): the dissociation curve of oxyhemoglobin (DCO) by the method of mixing, the intraerythrocyte 2,3, DPG level, the hemoglobin concentration and arterial blood parameters (PO2, PCO2, pH). These measurements were recorded before and after the general anaesthesia. The results were the following: a significant reduction of P50, measured under standard conditions (from 27.64 +/- 1.74 torr to 25.57 +/- 2.28, p less than or equal to 0.01) associated with a decrease in 2,3, DPG (from 0.94 +/- 0.31 mol/mol Hb at 0.64 +/- 0.24 p less than 0.01). Among the factors responsible for this variation in the affinity, it was proved that the volume of blood transfused was of importance as well as a decrease in body temperature during the operation. When the temperature is made to vary from 37 degrees C to 35 degrees C. the P50 ranges from 25.57 +/- 2.28 to 22.86 +/- 0.97 (p less than 0.01). To conclude the authors underline the importance of hypothermia and the volume of blood transfused (average time of preservation = 15 days) on the effects of the affinity of oxygen for hemoglobin."}
{"id": "PMID:23020", "title": "[Evaluation of per- and postoperative bleeding in 250 poro-metal total hip prostheses without cement].", "content": "Arthroplasty of the hip without cement in poro-metal (JUDET type) represents real progress. However, per-operative bleeding is greater, 48 per cent of patients losing more than 2000 ml and 25 per cent more than 3000 ml. Various factors may influence the degree of haemorrhage: the operative indication, the time of the operation and the administration of Calcium heparinate are studied. Postoperatively, overall blood loss then in relation to per-operative bleeding were evaluated.", "contents": "[Evaluation of per- and postoperative bleeding in 250 poro-metal total hip prostheses without cement]. Arthroplasty of the hip without cement in poro-metal (JUDET type) represents real progress. However, per-operative bleeding is greater, 48 per cent of patients losing more than 2000 ml and 25 per cent more than 3000 ml. Various factors may influence the degree of haemorrhage: the operative indication, the time of the operation and the administration of Calcium heparinate are studied. Postoperatively, overall blood loss then in relation to per-operative bleeding were evaluated."}
{"id": "PMID:23021", "title": "[Effects of high doses of morphinomimetics (fentanyl and fentathienyl) on the cerebral circulation in normal subjects].", "content": "The effects of large doses of morphinomimetics on the cerebral circulation were studied in 12 normal subjects (fentanyl 16 microgram/kg in 6 patients and fentathienyl 1.9 microgram/kg in 6 others). Mean hemispheric flow (corrected to a pCO2 of 40) changed from 50.8 +/- 4.4 ml/100 g/min in the conscious state to 50.3 +/- 25.1 under the influence of fentanyl, and flow in the grey matter from 78.8 +/- 10 to 84.3 +/- 65 ml/100 g/min. Mean flow changed from 49 +/- 3.1 ml/100 g/min in the conscious state to 55.5 +/- 10 under the influence of fentathienyl, flow in the grey matter increasing from 75 +/- 9 to 81.8 +/- 14.4. Whilst there was no variation in mean flow rates under the influence of morphinomimetics, individual behaviour was very variable, in particular in the case of fentanyl, the changes produced by fentathienyl being much more homogeneous. There was no obvious modification in the distribution of regional flow by these morphinomimetics. Individual variations in flow correlated perfectly with individual variations in cerebral oxygen consumption. Vascular reactivity to CO2 was increased b morphinomimetics. In one subject, fentanyl produced a very marked increase in cerebral blood flow (+ 104 p. 100) for which no explanation could be found.", "contents": "[Effects of high doses of morphinomimetics (fentanyl and fentathienyl) on the cerebral circulation in normal subjects]. The effects of large doses of morphinomimetics on the cerebral circulation were studied in 12 normal subjects (fentanyl 16 microgram/kg in 6 patients and fentathienyl 1.9 microgram/kg in 6 others). Mean hemispheric flow (corrected to a pCO2 of 40) changed from 50.8 +/- 4.4 ml/100 g/min in the conscious state to 50.3 +/- 25.1 under the influence of fentanyl, and flow in the grey matter from 78.8 +/- 10 to 84.3 +/- 65 ml/100 g/min. Mean flow changed from 49 +/- 3.1 ml/100 g/min in the conscious state to 55.5 +/- 10 under the influence of fentathienyl, flow in the grey matter increasing from 75 +/- 9 to 81.8 +/- 14.4. Whilst there was no variation in mean flow rates under the influence of morphinomimetics, individual behaviour was very variable, in particular in the case of fentanyl, the changes produced by fentathienyl being much more homogeneous. There was no obvious modification in the distribution of regional flow by these morphinomimetics. Individual variations in flow correlated perfectly with individual variations in cerebral oxygen consumption. Vascular reactivity to CO2 was increased b morphinomimetics. In one subject, fentanyl produced a very marked increase in cerebral blood flow (+ 104 p. 100) for which no explanation could be found."}
{"id": "PMID:23023", "title": "[Current aspects of gas gangrene, apropos of 47 cases collected over a 3-year period (1974-1976)].", "content": "On the basis of 47 cases of gas gangrene collected over the three year period between 1974 and 1976, the authors review the circumstances surrounding its development, the clinical features and the prognosis of the disorder which remains grave despite a well-defined therapeutic protocol combining surgery, antibiotics and hyperbaric oxygen. There would appear to be a real resurgence of the disease at the present time. Post-traumatic and surgical aetiologies predominate, giving rise to two types of gangrene: clostridial gas gangrene secondary to contamined wounds, with a quasi-constant vascular element, affecting predominantly the limbs, and nonclostridrial gangrene, the increasing prevalence of which involves essentially spetic abdomino-pelvic surgery. In the light of this study, prognosis would appear to be related to the underlying terrain in which the gangrene occurs, to certain features of the clinical picture and, above all, to the possibilities of early application of the complete therapeutic protocol. Strict prophylactic measures would alone seem capable of preventign the worrying increase in the number of cases of gas gangrene.", "contents": "[Current aspects of gas gangrene, apropos of 47 cases collected over a 3-year period (1974-1976)]. On the basis of 47 cases of gas gangrene collected over the three year period between 1974 and 1976, the authors review the circumstances surrounding its development, the clinical features and the prognosis of the disorder which remains grave despite a well-defined therapeutic protocol combining surgery, antibiotics and hyperbaric oxygen. There would appear to be a real resurgence of the disease at the present time. Post-traumatic and surgical aetiologies predominate, giving rise to two types of gangrene: clostridial gas gangrene secondary to contamined wounds, with a quasi-constant vascular element, affecting predominantly the limbs, and nonclostridrial gangrene, the increasing prevalence of which involves essentially spetic abdomino-pelvic surgery. In the light of this study, prognosis would appear to be related to the underlying terrain in which the gangrene occurs, to certain features of the clinical picture and, above all, to the possibilities of early application of the complete therapeutic protocol. Strict prophylactic measures would alone seem capable of preventign the worrying increase in the number of cases of gas gangrene."}
{"id": "PMID:23025", "title": "[Early complications after pleuro-pulmonary surgery. Study based on 217 operated patients].", "content": "In a study involving 217 patients who had undergone thoracotomy, the authors noted 85 complications in 77 patients with a mortality of 2.5 per cent. Respiratory complications were the most common but never ended in death. By contrast, cardiac complications are the most severe. The absence of mortality of respiratory origin is certainly the result of regourous pre-operative selection based upon overall and separate pulmonary function studies. The great rarity of pulmonary embolism is related to routine postoperative preventive heparin therapy.", "contents": "[Early complications after pleuro-pulmonary surgery. Study based on 217 operated patients]. In a study involving 217 patients who had undergone thoracotomy, the authors noted 85 complications in 77 patients with a mortality of 2.5 per cent. Respiratory complications were the most common but never ended in death. By contrast, cardiac complications are the most severe. The absence of mortality of respiratory origin is certainly the result of regourous pre-operative selection based upon overall and separate pulmonary function studies. The great rarity of pulmonary embolism is related to routine postoperative preventive heparin therapy."}
{"id": "PMID:23026", "title": "[Bacteroides fragilis septicemia].", "content": "On the basis of eight cases of Bacteroides fragilis septicaemia, the authors review recent data from the literature related to this topic. They first note the increasing prevalence, accounting for approximately 10 per cent of all septicaemias at the present time. They note that the most frequent portals of entry are sites of localised suppuration, related on the one hand to digestive or gynaecological surgery and, secondly, to the post-partum or post-abortum period. From a therapeutic standpoint, they stress the important role of imidazole derivatives (metronidazole or tinidazole) which are the most effective antibiotics at present. Certain authors even suggest their use on a preventive basis in high risk subjects.", "contents": "[Bacteroides fragilis septicemia]. On the basis of eight cases of Bacteroides fragilis septicaemia, the authors review recent data from the literature related to this topic. They first note the increasing prevalence, accounting for approximately 10 per cent of all septicaemias at the present time. They note that the most frequent portals of entry are sites of localised suppuration, related on the one hand to digestive or gynaecological surgery and, secondly, to the post-partum or post-abortum period. From a therapeutic standpoint, they stress the important role of imidazole derivatives (metronidazole or tinidazole) which are the most effective antibiotics at present. Certain authors even suggest their use on a preventive basis in high risk subjects."}
{"id": "PMID:23027", "title": "[Thiamine deficiency in chronic alcoholics. Value of pre- and postoperative treatment].", "content": "Thiamine deficiency in the chronic alcoholic would appear to have a triple origin: inadequate intake, absorption and utilisation. Its consequences are well known: peripheral neuropathy, WERNICKE and KORSAKOFF type encephalopathies and cardiac problems (with asystole at the extreme). The active principle of thiamine, TPP or cocarboxylase, is involved as a coenzyme of pyruvate decarboxylase and of alphaketoglutarate decarboxylase in the ocidative decarboxylation reactions of the Krebs cycle. TPP is involved as a coenzyme of transketolase in the transketolisation reactions of the pentose pathway. The stimation of transketolase demonstrates a deficiency in thiamine. Fourteen patients suffering from surgical ENT malignancies were involved in the present study. Seven patients received vitamin B therapy before and after the operation. The results showed a significant decrease in thiamine deficiency. Seven were used as controls and did not receive vitamin B therapy. Transketolase estimations showed and increase in the deficiency. Thiamine deficiency exists in the chronic alcoholic and may be corrected by the administration of B vitamins.", "contents": "[Thiamine deficiency in chronic alcoholics. Value of pre- and postoperative treatment]. Thiamine deficiency in the chronic alcoholic would appear to have a triple origin: inadequate intake, absorption and utilisation. Its consequences are well known: peripheral neuropathy, WERNICKE and KORSAKOFF type encephalopathies and cardiac problems (with asystole at the extreme). The active principle of thiamine, TPP or cocarboxylase, is involved as a coenzyme of pyruvate decarboxylase and of alphaketoglutarate decarboxylase in the ocidative decarboxylation reactions of the Krebs cycle. TPP is involved as a coenzyme of transketolase in the transketolisation reactions of the pentose pathway. The stimation of transketolase demonstrates a deficiency in thiamine. Fourteen patients suffering from surgical ENT malignancies were involved in the present study. Seven patients received vitamin B therapy before and after the operation. The results showed a significant decrease in thiamine deficiency. Seven were used as controls and did not receive vitamin B therapy. Transketolase estimations showed and increase in the deficiency. Thiamine deficiency exists in the chronic alcoholic and may be corrected by the administration of B vitamins."}
{"id": "PMID:23031", "title": "[Pulmonary mechanics and alveolar exchanges in the elderly with apparently healthy lungs. Preliminary study].", "content": "A group of ten elderly subjects who were apparently normal from the cardiac and pulmonary points of view, were selected on criteria of history, clinical findings, radiological and E.C.G. findings, with a view to a study of respiratory function based on two aspects: alveolar exchanges were assessed by measurement of the ductance of carbon monoxide and the elastic properties of the lung together with bronchial permeability. Although alveolar exchanges are little modified, one may note some pulmonary distension, especially in the smokers, together with a reduction in elasticity. The changes in bronchial permeability which affect the peripheral and central airways, are mainly found in smokers. One may determine the respective roles of extrinsic and intrinsic bronchial obstruction in these abnormalities. One may thus consider that, from the pulmonary point of view, the elderly patient faced with a surgical operation should be considered a high risk for respiratory decompensation, especially if he is, or has been, a smoker.", "contents": "[Pulmonary mechanics and alveolar exchanges in the elderly with apparently healthy lungs. Preliminary study]. A group of ten elderly subjects who were apparently normal from the cardiac and pulmonary points of view, were selected on criteria of history, clinical findings, radiological and E.C.G. findings, with a view to a study of respiratory function based on two aspects: alveolar exchanges were assessed by measurement of the ductance of carbon monoxide and the elastic properties of the lung together with bronchial permeability. Although alveolar exchanges are little modified, one may note some pulmonary distension, especially in the smokers, together with a reduction in elasticity. The changes in bronchial permeability which affect the peripheral and central airways, are mainly found in smokers. One may determine the respective roles of extrinsic and intrinsic bronchial obstruction in these abnormalities. One may thus consider that, from the pulmonary point of view, the elderly patient faced with a surgical operation should be considered a high risk for respiratory decompensation, especially if he is, or has been, a smoker."}
{"id": "PMID:23032", "title": "[The aged heart in surgery].", "content": "The risk of surgical operation is increased by the presence of heart disease. The statistics are too limited for this risk to be expressed more precisely. The heart in the elderly is no longer a normal heart. The myocardial functional reserve declines, the quality of the A.V. conduction is not always good and vascular fibrosis progresses. Surgical operation thus increases the risk of a cardio-vascular accident. One should distinguish the risk due simply to old age. The existence of known heart disease often leads to heart failure which is difficult to treat. The great risk of surgical operation is then the risk of overloading the heart. In the absence of known heart disease, one should beware of latent coronary insufficiency. The major risk is then hypoxia. The special problem of degenerative A.V. conduction disorders may require the insertion of a pace-maker. Pre-op\u00e9ratoire cardio-vascular assessment is thus necessary in the elderly subject. It should, however, remain simple. Careful history and auscultation, verification of the periph\u00e9ral arteries, chest XRay and E.C.G.", "contents": "[The aged heart in surgery]. The risk of surgical operation is increased by the presence of heart disease. The statistics are too limited for this risk to be expressed more precisely. The heart in the elderly is no longer a normal heart. The myocardial functional reserve declines, the quality of the A.V. conduction is not always good and vascular fibrosis progresses. Surgical operation thus increases the risk of a cardio-vascular accident. One should distinguish the risk due simply to old age. The existence of known heart disease often leads to heart failure which is difficult to treat. The great risk of surgical operation is then the risk of overloading the heart. In the absence of known heart disease, one should beware of latent coronary insufficiency. The major risk is then hypoxia. The special problem of degenerative A.V. conduction disorders may require the insertion of a pace-maker. Pre-op\u00e9ratoire cardio-vascular assessment is thus necessary in the elderly subject. It should, however, remain simple. Careful history and auscultation, verification of the periph\u00e9ral arteries, chest XRay and E.C.G."}
{"id": "PMID:23035", "title": "[Postoperative nitrogen balance in the elderly. Effects of an anti-aldosterone drug].", "content": "A previous study led us to believe that the use of anti-aldosterone treatment in the immediate post-operative phase of abdominal surgery ensured energy saving in nitrogen balance. In fact, if massive restoral of water and electrolytes proves necessary, the optimum sodium and potassium intake during the use of soludactone, does not appear to be the only factor liable to influence significantly nitrogen balance or, at least, positive nitrogen balance. We are now attempting to apply our experience to the same problem in the elderly.", "contents": "[Postoperative nitrogen balance in the elderly. Effects of an anti-aldosterone drug]. A previous study led us to believe that the use of anti-aldosterone treatment in the immediate post-operative phase of abdominal surgery ensured energy saving in nitrogen balance. In fact, if massive restoral of water and electrolytes proves necessary, the optimum sodium and potassium intake during the use of soludactone, does not appear to be the only factor liable to influence significantly nitrogen balance or, at least, positive nitrogen balance. We are now attempting to apply our experience to the same problem in the elderly."}
{"id": "PMID:23036", "title": "[The brain in the aged].", "content": "Under the very broad term of brain in the elderly, we cannot consider exhaustively all the anatomical, physiopathological and pathological aspect and, still less, the therapeutic possibilities in diseases of the anesthetist should know concerning the special characteristics of this aging organ. First are recalled the anatomical, macro and microscopic data of the senile brain. The metabolic characteristics are then considered. Investigations which may give the clinician information concerning the organic state and metabolic capacities of the brain of the elderly subject, e.g. cerebral blood flow, fundus oculi, E.E.G. brain arteriography, tacography or tomodensitometry by scanner, are consideres. But in practice, they are difficult to use and their data are only relatively reliable, i.e. clinical examination is of great imporatnce and the overall impression prevails. The therapeutic possibilities are limited and in these elderly subjects with cerebral metabolism in unstable equilibrium, one should be circumspect and careful in treatment.", "contents": "[The brain in the aged]. Under the very broad term of brain in the elderly, we cannot consider exhaustively all the anatomical, physiopathological and pathological aspect and, still less, the therapeutic possibilities in diseases of the anesthetist should know concerning the special characteristics of this aging organ. First are recalled the anatomical, macro and microscopic data of the senile brain. The metabolic characteristics are then considered. Investigations which may give the clinician information concerning the organic state and metabolic capacities of the brain of the elderly subject, e.g. cerebral blood flow, fundus oculi, E.E.G. brain arteriography, tacography or tomodensitometry by scanner, are consideres. But in practice, they are difficult to use and their data are only relatively reliable, i.e. clinical examination is of great imporatnce and the overall impression prevails. The therapeutic possibilities are limited and in these elderly subjects with cerebral metabolism in unstable equilibrium, one should be circumspect and careful in treatment."}
{"id": "PMID:23037", "title": "[Confusional states in geriatrics].", "content": "Illustrated by clinical reports, this study attempts to demonstrate the practical and didactic interest of various somatopsychological correlations in geriatrics. The confusional state in the elderly has no specific etiopathogenesis. It is only the expression, often disconcerting, of a method of cerebral suffering and the clinician should be aware of its various presentations. The precipitating factors are not only of organic or iatrogenic origin, but often psychological. Any change is considered by the elderly patient as dangerous and worrying. Our perfectly justified fear of inaction and passivity together with a desire for rapid efficacy, should not lead us to forget that in geriatrics more than in any other branch of medicine, a prudent attitude in therapeutics is most likely to be successful.", "contents": "[Confusional states in geriatrics]. Illustrated by clinical reports, this study attempts to demonstrate the practical and didactic interest of various somatopsychological correlations in geriatrics. The confusional state in the elderly has no specific etiopathogenesis. It is only the expression, often disconcerting, of a method of cerebral suffering and the clinician should be aware of its various presentations. The precipitating factors are not only of organic or iatrogenic origin, but often psychological. Any change is considered by the elderly patient as dangerous and worrying. Our perfectly justified fear of inaction and passivity together with a desire for rapid efficacy, should not lead us to forget that in geriatrics more than in any other branch of medicine, a prudent attitude in therapeutics is most likely to be successful."}
{"id": "PMID:23039", "title": "[Age and other factors in the prognosis and operative indications for brain surgery].", "content": "Attempt at evaluation of the operative risk depending on seven factors. 1--For benign tumours (Example: meningiomas): 1--greater than 65 years; 2--functional insufficiency, depending on the type of tumour; 3--the volume of the tumour; 4--site of the tumour; 5--foreseeable operative difficulties; 6--the importance of intra-cranial hypertension and the level of pre-operative consciousness; 7--life expectancy, quantitative and qualitative. II--Extrapolation of the previous equation to malignant tumours, chronic sub-dural hematoma, intra-cerebral hematoma and surgery of pain.", "contents": "[Age and other factors in the prognosis and operative indications for brain surgery]. Attempt at evaluation of the operative risk depending on seven factors. 1--For benign tumours (Example: meningiomas): 1--greater than 65 years; 2--functional insufficiency, depending on the type of tumour; 3--the volume of the tumour; 4--site of the tumour; 5--foreseeable operative difficulties; 6--the importance of intra-cranial hypertension and the level of pre-operative consciousness; 7--life expectancy, quantitative and qualitative. II--Extrapolation of the previous equation to malignant tumours, chronic sub-dural hematoma, intra-cerebral hematoma and surgery of pain."}
{"id": "PMID:23041", "title": "[Admission and treatment of 592 patients over 70 years in an intensive care unit].", "content": "Using an IBM 3741 computer, the authors analysed 592 case records of patients aged over 70 years, admitted to hospital on an intensive care unit, age appears to be an important factor in determining the prognosis of numerous diseases without, however, being a criteria for rejection of admission of these patients to an intensive care unit. The fragility of these patients leads one to consider the following parameters: 1--the degree of resuscitation is assessed by quantification of the therapeutic means. As for other patients, survival varies inversely in relation to the important of the therapeutic means, but in the case of the elderly patient, there is a definite difference in the correlation mortality-therapeutic index towards aggravation, so one may determine a ceiling above which survival is not possible; 2--duration of the intensive care is very important. In most cases, the decisive point is situated on the 3rd or 4th day of care, at which time the decision to continue or stop treatment may be considered in the light of the patient's progress.", "contents": "[Admission and treatment of 592 patients over 70 years in an intensive care unit]. Using an IBM 3741 computer, the authors analysed 592 case records of patients aged over 70 years, admitted to hospital on an intensive care unit, age appears to be an important factor in determining the prognosis of numerous diseases without, however, being a criteria for rejection of admission of these patients to an intensive care unit. The fragility of these patients leads one to consider the following parameters: 1--the degree of resuscitation is assessed by quantification of the therapeutic means. As for other patients, survival varies inversely in relation to the important of the therapeutic means, but in the case of the elderly patient, there is a definite difference in the correlation mortality-therapeutic index towards aggravation, so one may determine a ceiling above which survival is not possible; 2--duration of the intensive care is very important. In most cases, the decisive point is situated on the 3rd or 4th day of care, at which time the decision to continue or stop treatment may be considered in the light of the patient's progress."}
{"id": "PMID:23045", "title": "[General anesthesia for ophthalmic surgery in patients over 80 years].", "content": "Among 150 elderly ophthalmological patients over 80 years old, only seven patients did not undergo a general anaesthesia, because of respiratory insufficiency and/or ventricular extrasystoles. The other, 143 patients underwent 178 operations under general anaesthesia with minimal per and postsurgical complications. Therefore, it seems unjustified to deny the benefit of general anaesthesia to ophthalmologic surgical patients more than 80 years old.", "contents": "[General anesthesia for ophthalmic surgery in patients over 80 years]. Among 150 elderly ophthalmological patients over 80 years old, only seven patients did not undergo a general anaesthesia, because of respiratory insufficiency and/or ventricular extrasystoles. The other, 143 patients underwent 178 operations under general anaesthesia with minimal per and postsurgical complications. Therefore, it seems unjustified to deny the benefit of general anaesthesia to ophthalmologic surgical patients more than 80 years old."}
{"id": "PMID:23046", "title": "[Methods and indications for low peridural analgesia in the aged. Report of 300 cases].", "content": "Continuous peridural analgesia took a long time to be accepted in current practice in surgery of the elderly, owing to the apprehensions for the possible cardiovascular consequences and also, the difficulty in using this form of anaesthesia in the elderly. The experience of more than 300 cases, collected in the Nice department of Anesthetics and Intensive Care, has shown that: 1--technical failures are exceptional with routine use of prior epidurography; 2--its indications depend on the site and type of surgery and on the clinical conditions of the patient; 3--until now, there have been no severe complications due to this method whatever the degree and number of morbid conditions; 4--in the elderly subject, the importance of problems of pre and post-operative analgesia have led us to enlarge the indications for long-term peridural analgesia. Peridural anesthesia may be used as a routine when the site of the operation involves areas situated below the IXth metamere. This shows its importance in surgery in the elderly.", "contents": "[Methods and indications for low peridural analgesia in the aged. Report of 300 cases]. Continuous peridural analgesia took a long time to be accepted in current practice in surgery of the elderly, owing to the apprehensions for the possible cardiovascular consequences and also, the difficulty in using this form of anaesthesia in the elderly. The experience of more than 300 cases, collected in the Nice department of Anesthetics and Intensive Care, has shown that: 1--technical failures are exceptional with routine use of prior epidurography; 2--its indications depend on the site and type of surgery and on the clinical conditions of the patient; 3--until now, there have been no severe complications due to this method whatever the degree and number of morbid conditions; 4--in the elderly subject, the importance of problems of pre and post-operative analgesia have led us to enlarge the indications for long-term peridural analgesia. Peridural anesthesia may be used as a routine when the site of the operation involves areas situated below the IXth metamere. This shows its importance in surgery in the elderly."}
{"id": "PMID:23048", "title": "[A comparative study of the course of aged patients with hip surgery].", "content": "On an orthopedic surgical unit we studied the course of patients aged over 70 years who had undergone surgical operation on the hip in 1974 and 1975. Distinguishing the pre-op\u00e9rative, per-operative and post-operative stages, we used firstly, the distribution according to age and sex, the past history, the laboratory findings, the type of operation and the type of anesthetic. Then, we carried out a comparative analysis in relation to the past history, the post-operative complications and the deaths.", "contents": "[A comparative study of the course of aged patients with hip surgery]. On an orthopedic surgical unit we studied the course of patients aged over 70 years who had undergone surgical operation on the hip in 1974 and 1975. Distinguishing the pre-op\u00e9rative, per-operative and post-operative stages, we used firstly, the distribution according to age and sex, the past history, the laboratory findings, the type of operation and the type of anesthetic. Then, we carried out a comparative analysis in relation to the past history, the post-operative complications and the deaths."}
{"id": "PMID:23050", "title": "[Pharmacoloby of the bronchomotor tonus during anesthesia].", "content": "In a patient under general anesthesia, the occurrence of bronchospasm can be readily treated provided the cause is diagnosed early. The corrective drugs to dilate are readily available: atropine, epinephrine and theophylline. In the choice of preanesthetics, anesthetics and adjuvants, it is important to remember that there are differences in the bronchomotor effects; most curareform drugs constrict except pancuronium; most inhalational anesthetics dilate in contrast to intravenous anesthetics. In the event that bronchospasm cannot be re relieved by drugs, intubation and assisted breating can be applied to maintain adequate gas exchange in the alveoli.", "contents": "[Pharmacoloby of the bronchomotor tonus during anesthesia]. In a patient under general anesthesia, the occurrence of bronchospasm can be readily treated provided the cause is diagnosed early. The corrective drugs to dilate are readily available: atropine, epinephrine and theophylline. In the choice of preanesthetics, anesthetics and adjuvants, it is important to remember that there are differences in the bronchomotor effects; most curareform drugs constrict except pancuronium; most inhalational anesthetics dilate in contrast to intravenous anesthetics. In the event that bronchospasm cannot be re relieved by drugs, intubation and assisted breating can be applied to maintain adequate gas exchange in the alveoli."}
{"id": "PMID:23051", "title": "[Metabolic and pharmacologic interactions on the bronchial tonus].", "content": "After reminding data concerning the part played by the as a rule antagonist cAMP system in moticity of the smooth muscle fibers in general and of the bronchial fibers in particular, the authors study the different types of interaction on bronchial muscular fibers which have been discribed. It is concerning the adrenergic fibers that the experimental and clinical data are prevalent (role of bronchial alpha- and beta2- receptors) and the authors point especially to their own studies performed since 1964 concerning the alpha1- -bronchoconstrictive component and progressive auto-inhibition of the bronchial beta2- receptors. But autacoids (serotonin, bradykinin, histamine and prostaglandines) and with the stimulating or inhibiting agents of the beta2 -receptors also begin to be recognized.", "contents": "[Metabolic and pharmacologic interactions on the bronchial tonus]. After reminding data concerning the part played by the as a rule antagonist cAMP system in moticity of the smooth muscle fibers in general and of the bronchial fibers in particular, the authors study the different types of interaction on bronchial muscular fibers which have been discribed. It is concerning the adrenergic fibers that the experimental and clinical data are prevalent (role of bronchial alpha- and beta2- receptors) and the authors point especially to their own studies performed since 1964 concerning the alpha1- -bronchoconstrictive component and progressive auto-inhibition of the bronchial beta2- receptors. But autacoids (serotonin, bradykinin, histamine and prostaglandines) and with the stimulating or inhibiting agents of the beta2 -receptors also begin to be recognized."}
{"id": "PMID:23053", "title": "[Determination of global diffusion of CO2 and its partial components under assisted respiration. Technical problems and practical value in respiratory resuscitation].", "content": "A study of partial CO2 ductance has been performed in patients under assisted ventilation. The authors propose methods for simultaneous measurement of paCO2, PAECO2, PECO2 and PICO2. This methodology is used in patients presenting different conditions accounting for respiratory resuscitation: barbiturate poisoning with healthy lungs, bronchial stasis, acute lung involvement, obstructive bronchopneumopathy and pulmonary embolism.", "contents": "[Determination of global diffusion of CO2 and its partial components under assisted respiration. Technical problems and practical value in respiratory resuscitation]. A study of partial CO2 ductance has been performed in patients under assisted ventilation. The authors propose methods for simultaneous measurement of paCO2, PAECO2, PECO2 and PICO2. This methodology is used in patients presenting different conditions accounting for respiratory resuscitation: barbiturate poisoning with healthy lungs, bronchial stasis, acute lung involvement, obstructive bronchopneumopathy and pulmonary embolism."}
{"id": "PMID:23054", "title": "[Bronchial spasm and bronchial motoricity].", "content": "The author recalls the phenomena which control bronchomotility, without a personal study but based on recent bibliography. After recalling the bronchial nerve supply, the chemical intermediates, the various responses of the bronchial tree to autacoids, the author recalls the association of anesthesia and bronchospasm. Although the bronchial reactions of histaminic origin are the most frequent, mechanical or chemical irritation is recalled with an elementary description of \"irritant receptors\" and stretch receptors. Finally, the other causes of bronchial narrowing are considered: vago-sympathetic imbalance, atopic background, influence of the anesthetic on vagal tone or on adrenal medullary secretion.", "contents": "[Bronchial spasm and bronchial motoricity]. The author recalls the phenomena which control bronchomotility, without a personal study but based on recent bibliography. After recalling the bronchial nerve supply, the chemical intermediates, the various responses of the bronchial tree to autacoids, the author recalls the association of anesthesia and bronchospasm. Although the bronchial reactions of histaminic origin are the most frequent, mechanical or chemical irritation is recalled with an elementary description of \"irritant receptors\" and stretch receptors. Finally, the other causes of bronchial narrowing are considered: vago-sympathetic imbalance, atopic background, influence of the anesthetic on vagal tone or on adrenal medullary secretion."}
{"id": "PMID:23055", "title": "[Peroperative pneumothorax].", "content": "Pneumothorax during operation is always clinically serious. The symptoms are usually sudden cyanosis, accompanied by cardio-vascular collapse and difficulty or even impossibility to ventilate owing to increased pressures of insufflation. Immediate or secondary bilateral pneumothorax is relatively common, then may appear associated complications such as subcutaneous emphysema or pneumo-mediastinum. Early diagnosis is necessary to apply simple treatment and avoid a course which may be rapidly fatal. The authors report 3 cases of pneumothorax during anesthesia and consider the clinical forms, the mechanisms and causes of this accident.", "contents": "[Peroperative pneumothorax]. Pneumothorax during operation is always clinically serious. The symptoms are usually sudden cyanosis, accompanied by cardio-vascular collapse and difficulty or even impossibility to ventilate owing to increased pressures of insufflation. Immediate or secondary bilateral pneumothorax is relatively common, then may appear associated complications such as subcutaneous emphysema or pneumo-mediastinum. Early diagnosis is necessary to apply simple treatment and avoid a course which may be rapidly fatal. The authors report 3 cases of pneumothorax during anesthesia and consider the clinical forms, the mechanisms and causes of this accident."}
{"id": "PMID:23056", "title": "[Significance of capnography in cases of pneumothorax occurring during artificial respiration].", "content": "The author reports the case of a premature new-born presenting a respiratory distress syndrome who was ventilated through a tracheal tube and in whom an artificial pneumothorax developed. Capnography quickly provided accurate data allowing an adaptation of therapy.", "contents": "[Significance of capnography in cases of pneumothorax occurring during artificial respiration]. The author reports the case of a premature new-born presenting a respiratory distress syndrome who was ventilated through a tracheal tube and in whom an artificial pneumothorax developed. Capnography quickly provided accurate data allowing an adaptation of therapy."}
{"id": "PMID:23057", "title": "[Inhalation of regurgitated fluid during anesthesia].", "content": "Since the observations of HALL in 1940 and MENDELSON in 1946 numerous clinical and experimental reports have completed our knowledge of the consequences of inhalation of fluid during anesthesia. Apart from the pulmonary signs, this syndrome includes cardiovascular signs. The course of the pulmonary disease is often unfavourable. Frequently, diagnostic problems are raised a posteriori in the light of respiratory distress and abnormal pulmonary radiological signs. It is then sometimes difficult to distinguish the role of the position on the operating table, the role of massive transfusion without adequate filtration, a state of shock, or unrecognised inhalation of fluid. The various problems are exposed. The interest of prevention and treatment is discussed.", "contents": "[Inhalation of regurgitated fluid during anesthesia]. Since the observations of HALL in 1940 and MENDELSON in 1946 numerous clinical and experimental reports have completed our knowledge of the consequences of inhalation of fluid during anesthesia. Apart from the pulmonary signs, this syndrome includes cardiovascular signs. The course of the pulmonary disease is often unfavourable. Frequently, diagnostic problems are raised a posteriori in the light of respiratory distress and abnormal pulmonary radiological signs. It is then sometimes difficult to distinguish the role of the position on the operating table, the role of massive transfusion without adequate filtration, a state of shock, or unrecognised inhalation of fluid. The various problems are exposed. The interest of prevention and treatment is discussed."}
{"id": "PMID:23058", "title": "[Complications following cementing of joint prosthesis].", "content": "The authors studied changes in the level of lactate dehydrogenase during insertion of hip prostheseis fixed with methyl methacrylate cement. Thirty patients were studied here. In 23 of them, the L.D.H. isoenzymes were estimated. The variations in these enzymes appear 3 hours after the second fixation with cement: rise in L.D.H., isoenzyme 5, (of skeletal muscle origin) of isoenzymes 3 and 4, (of pulmonary origin). This is a sign of pulmonary involvement even in the absence of clinical signs.", "contents": "[Complications following cementing of joint prosthesis]. The authors studied changes in the level of lactate dehydrogenase during insertion of hip prostheseis fixed with methyl methacrylate cement. Thirty patients were studied here. In 23 of them, the L.D.H. isoenzymes were estimated. The variations in these enzymes appear 3 hours after the second fixation with cement: rise in L.D.H., isoenzyme 5, (of skeletal muscle origin) of isoenzymes 3 and 4, (of pulmonary origin). This is a sign of pulmonary involvement even in the absence of clinical signs."}
{"id": "PMID:23059", "title": "[Pulmonary edema due to peroperative overload or anesthetic awakening].", "content": "This report gives details of the clinical characteristics, the circumstances of onset and the treatment. There is always a blood volume overload, but the absolute value does not differ radically from that often necessary to maintain during heavy or hemorrhagic surgery, good hemodynamic conditions. The association with other factors seems necessary, in particular the redistribution in blood volum which occurs during awakening or reduction in anesthesia. Treatment by reduction in blood volume (bleeding, diuretics) is often insufficient. Many cases require mechanical ventilation for several days. Ventilation under continuous positive pressure may even be essential. The frequency of these accidents may even rise for several reasons: vasoplegic anesthesia, routine restoration of blood volume for hemodynamic reasons or to protect the kidneys, occasional failure of C.V.P. as means of control of this restoration, wider and wider use of red cells concentrates and colloids without precise knowledge of their properties.", "contents": "[Pulmonary edema due to peroperative overload or anesthetic awakening]. This report gives details of the clinical characteristics, the circumstances of onset and the treatment. There is always a blood volume overload, but the absolute value does not differ radically from that often necessary to maintain during heavy or hemorrhagic surgery, good hemodynamic conditions. The association with other factors seems necessary, in particular the redistribution in blood volum which occurs during awakening or reduction in anesthesia. Treatment by reduction in blood volume (bleeding, diuretics) is often insufficient. Many cases require mechanical ventilation for several days. Ventilation under continuous positive pressure may even be essential. The frequency of these accidents may even rise for several reasons: vasoplegic anesthesia, routine restoration of blood volume for hemodynamic reasons or to protect the kidneys, occasional failure of C.V.P. as means of control of this restoration, wider and wider use of red cells concentrates and colloids without precise knowledge of their properties."}
{"id": "PMID:23060", "title": "[Anaphylactic reactions observed with anesthetics and adjuvants].", "content": "The author reports an inquiry concerning 66 patients who all had an anaphylactoid reaction. The hour of onset, the type of reaction, (skin, bronchial or systemic), their association, the drugs responsible, and the diagnostic difficulties are reviewed. In this respect, in relation to the results of the above inquiry and the data in the literature, the skin and bronchial reactions are described, and the signs of anaphylactic shock recalled. The substances possible are then reviewed with the possible correlation between the type of accident and the drug responsible. Finally the role of macromolecules is discussed.", "contents": "[Anaphylactic reactions observed with anesthetics and adjuvants]. The author reports an inquiry concerning 66 patients who all had an anaphylactoid reaction. The hour of onset, the type of reaction, (skin, bronchial or systemic), their association, the drugs responsible, and the diagnostic difficulties are reviewed. In this respect, in relation to the results of the above inquiry and the data in the literature, the skin and bronchial reactions are described, and the signs of anaphylactic shock recalled. The substances possible are then reviewed with the possible correlation between the type of accident and the drug responsible. Finally the role of macromolecules is discussed."}
{"id": "PMID:23062", "title": "[Effects of anesthesia and surgery on certain parameters of humoral immunity].", "content": "Research on certain parameters of humoral immunity was undertaken in 10 patients who had undergone a major surgical operation. The control subjects were chosen among 10 subjects in good health. The tests were carried out within 24-72 hours after the operation. The determination of cytolytic lymphocyte activity, in the presence of specific antibodies, was strongly lowered in the postoperative period. This was also the case with the capacity to form EAC lymphocyte rosettes. Finally total serum complement was lowered significantly whereas factor C3 remained normal. These results show a change in humoral immunity in the postoperative period together with a reduction in complement activity.", "contents": "[Effects of anesthesia and surgery on certain parameters of humoral immunity]. Research on certain parameters of humoral immunity was undertaken in 10 patients who had undergone a major surgical operation. The control subjects were chosen among 10 subjects in good health. The tests were carried out within 24-72 hours after the operation. The determination of cytolytic lymphocyte activity, in the presence of specific antibodies, was strongly lowered in the postoperative period. This was also the case with the capacity to form EAC lymphocyte rosettes. Finally total serum complement was lowered significantly whereas factor C3 remained normal. These results show a change in humoral immunity in the postoperative period together with a reduction in complement activity."}
{"id": "PMID:23063", "title": "In vivo function tests of the effect of tilorone and niridazole on cell-mediated immunity in chickens.", "content": "The need for effective, safe, specific cellular immune suppression in avian research led to the study of effects of tilorone and niridazole on cell-mediated immunity of chickens. Two in vivo tests for cell-mediated immunity function were used--the graft-vs-host (GvH) test and the delayed hypersensitivity (DH) test. Humoral immunity was evaluated by measuring natural hemagglutination (HA) titers against rabbit red blood cells. Intraperitoneal administration of tilorone to young chickens appeared to have severe toxic side effects and was of little value as an immune suppressant. Oral administration of tilorone to 6-week-old chickens caused DH suppression, but no marked effect was seen on GvH reactions or HA titers. Toxicosis appeared less severe. Oral administration of niridazole to 6-week-old birds caused nearly complete loss of GvH and DH reactivity but caused an increase in HA titers. General toxic effects of niridazole were not apparent.", "contents": "In vivo function tests of the effect of tilorone and niridazole on cell-mediated immunity in chickens. The need for effective, safe, specific cellular immune suppression in avian research led to the study of effects of tilorone and niridazole on cell-mediated immunity of chickens. Two in vivo tests for cell-mediated immunity function were used--the graft-vs-host (GvH) test and the delayed hypersensitivity (DH) test. Humoral immunity was evaluated by measuring natural hemagglutination (HA) titers against rabbit red blood cells. Intraperitoneal administration of tilorone to young chickens appeared to have severe toxic side effects and was of little value as an immune suppressant. Oral administration of tilorone to 6-week-old chickens caused DH suppression, but no marked effect was seen on GvH reactions or HA titers. Toxicosis appeared less severe. Oral administration of niridazole to 6-week-old birds caused nearly complete loss of GvH and DH reactivity but caused an increase in HA titers. General toxic effects of niridazole were not apparent."}
{"id": "PMID:23064", "title": "Pharmacological and psychological determinants of smoking. A New York University honors program lecture.", "content": "Arguments for and against low-nicotine cigarettes are examined by considering evidence relevant to the gratification of smoking and to nicotine as an addicting agent. A variety of studies indicates that smokers regulate nicotine intake and that variations in smoking rate that customarily have been interpreted in psychological terms are better understood as attempts to regulate nicotine. These findings bring into question the justification for the low-nicotine cigarette campaign.", "contents": "Pharmacological and psychological determinants of smoking. A New York University honors program lecture. Arguments for and against low-nicotine cigarettes are examined by considering evidence relevant to the gratification of smoking and to nicotine as an addicting agent. A variety of studies indicates that smokers regulate nicotine intake and that variations in smoking rate that customarily have been interpreted in psychological terms are better understood as attempts to regulate nicotine. These findings bring into question the justification for the low-nicotine cigarette campaign."}
{"id": "PMID:23067", "title": "[E. coli penicillin amidase. Physico-chemical properties of the enzyme covalently bound to the 2-(3'-amino-4'-methoxyphenyl)-sulfonylethyl ester of cellulose].", "content": "The effect of the procedure of the enzyme binding with the carrier on the properties of the heterogenous catalyst obtained by covalent binding of penicillinamidase (PA) with cellulose 2-(3'-amino-4'-methoxyphenyl)-sulphonylethyl ether by means of the bifunctional reagent, i.e. glutaric aldehyde was studied. It was shown that the amount of the bound enzyme increased with a rise in the amount of the enzyme taken for the binding, while the binding efficiency characterizing the part of the active enzyme in the total amount of the bound PA decreased practically 2 times. The use of the enzyme preparations with different purify levels for the binding provided differentiation of the effects resulting in the activity loss on immobilization. In other words it provided separate estimation of the inactivation effect of the matrix and the immobilization procedure, as well as the interaction of the enzyme molecules with each other and other protein molecules.", "contents": "[E. coli penicillin amidase. Physico-chemical properties of the enzyme covalently bound to the 2-(3'-amino-4'-methoxyphenyl)-sulfonylethyl ester of cellulose]. The effect of the procedure of the enzyme binding with the carrier on the properties of the heterogenous catalyst obtained by covalent binding of penicillinamidase (PA) with cellulose 2-(3'-amino-4'-methoxyphenyl)-sulphonylethyl ether by means of the bifunctional reagent, i.e. glutaric aldehyde was studied. It was shown that the amount of the bound enzyme increased with a rise in the amount of the enzyme taken for the binding, while the binding efficiency characterizing the part of the active enzyme in the total amount of the bound PA decreased practically 2 times. The use of the enzyme preparations with different purify levels for the binding provided differentiation of the effects resulting in the activity loss on immobilization. In other words it provided separate estimation of the inactivation effect of the matrix and the immobilization procedure, as well as the interaction of the enzyme molecules with each other and other protein molecules."}
{"id": "PMID:23068", "title": "[Physiochemical properties of 7-aminoacetoxycephalosporanic acid].", "content": "Potentiometric titration of the zwitter-ion of 7-aminoacetoxycephalosporanic acid (7-ACA) was performed and the constants of its ionization were estimated. The minimum solubility of the 7-ACA zwitter-ion (20 degrees C, 0.1 M NaCl) was determined and the solubility curve of 7-ACA at wide pH ranges was calculated. Equilibrium of the cationic, zwitter-ionic and anionic forms of 7-ACA was estimated as dependent on pH.", "contents": "[Physiochemical properties of 7-aminoacetoxycephalosporanic acid]. Potentiometric titration of the zwitter-ion of 7-aminoacetoxycephalosporanic acid (7-ACA) was performed and the constants of its ionization were estimated. The minimum solubility of the 7-ACA zwitter-ion (20 degrees C, 0.1 M NaCl) was determined and the solubility curve of 7-ACA at wide pH ranges was calculated. Equilibrium of the cationic, zwitter-ionic and anionic forms of 7-ACA was estimated as dependent on pH."}
{"id": "PMID:23070", "title": "[Use of a polarographic method for determining trichothecin].", "content": "The polarographic behaviour of trichothecin was studied. It was shown that the antibiotic could be detected in solutions at concentrations of 7.10(-7) moles with the help of the polarographic method. Conditions for the polarographic determination of trichothecin in fermentation broth were developed. The error was not more than 3 per cent. The reliability of the results was shown by statistical treatment of data performed in accordance with the requirement of the USSR State Pharmacopeia, X ed., prescribing that the precision of the assay is such that the fiducial limits at p = 95 per cent deviate from the average value by not more than 5 per cent. Comparison of the results of trichothecin determination in the fermentation broth with the polarographic and biological methods showed no significant difference. Therefore, the polarographic method may be recommended for trichothecin determination in the fermentation broth.", "contents": "[Use of a polarographic method for determining trichothecin]. The polarographic behaviour of trichothecin was studied. It was shown that the antibiotic could be detected in solutions at concentrations of 7.10(-7) moles with the help of the polarographic method. Conditions for the polarographic determination of trichothecin in fermentation broth were developed. The error was not more than 3 per cent. The reliability of the results was shown by statistical treatment of data performed in accordance with the requirement of the USSR State Pharmacopeia, X ed., prescribing that the precision of the assay is such that the fiducial limits at p = 95 per cent deviate from the average value by not more than 5 per cent. Comparison of the results of trichothecin determination in the fermentation broth with the polarographic and biological methods showed no significant difference. Therefore, the polarographic method may be recommended for trichothecin determination in the fermentation broth."}
{"id": "PMID:23066", "title": "[Detection of weak graft-versus-host reactions by the suppressive effect on the immune response (author's transl)].", "content": "Weak graft-versus-host reactions induced between H-2 compatible strains are not detected by the splenomegaly assay in newborn mice. Similarly the proliferative response in the mixed lymphocyte culture or the popliteal lymph node assay was not extensive in some combinations. On the contrary, the inhibition of the specific immune response to heterologous red cells was observed when graft occurred from 15 days before immunization. So the weak graft-versus-host reactions appeared to be easily detected by the suppressive effect on antibody synthesis.", "contents": "[Detection of weak graft-versus-host reactions by the suppressive effect on the immune response (author's transl)]. Weak graft-versus-host reactions induced between H-2 compatible strains are not detected by the splenomegaly assay in newborn mice. Similarly the proliferative response in the mixed lymphocyte culture or the popliteal lymph node assay was not extensive in some combinations. On the contrary, the inhibition of the specific immune response to heterologous red cells was observed when graft occurred from 15 days before immunization. So the weak graft-versus-host reactions appeared to be easily detected by the suppressive effect on antibody synthesis."}
{"id": "PMID:23072", "title": "Discovery of an agent in wastewater sludge that reduces the heat required to inactivate reovirus.", "content": "An agent that causes heat inactivation of reovirus to occur at reduced temperatures has been found in both raw and anaerobically digested sludge. This agent is originally associated with sludge solids but can be washed from these solids by blending with water. The activity of the agent was considerably greater in alkaline than in acid solutions, probably because it is insoluble at low pH. The agent was shown to be nonvolatile and heat stable up to 300 degrees C but was inactivated within 30 min at 400 degrees C. The rate of heat inactivation of reovirus by the agent was found to occur in a bimodal fashion and to be relatively rapid, even at 35 degrees C. Finally, it was found that this agent did not accelerate heat inactivation of poliovirus, but instead may be the component of sludge previously found to protect poliovirus against inactivation by heat.", "contents": "Discovery of an agent in wastewater sludge that reduces the heat required to inactivate reovirus. An agent that causes heat inactivation of reovirus to occur at reduced temperatures has been found in both raw and anaerobically digested sludge. This agent is originally associated with sludge solids but can be washed from these solids by blending with water. The activity of the agent was considerably greater in alkaline than in acid solutions, probably because it is insoluble at low pH. The agent was shown to be nonvolatile and heat stable up to 300 degrees C but was inactivated within 30 min at 400 degrees C. The rate of heat inactivation of reovirus by the agent was found to occur in a bimodal fashion and to be relatively rapid, even at 35 degrees C. Finally, it was found that this agent did not accelerate heat inactivation of poliovirus, but instead may be the component of sludge previously found to protect poliovirus against inactivation by heat."}
{"id": "PMID:23077", "title": "Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after short (less than 30 minutes) first febrile convulsions in children.", "content": "Twenty-nine infants and children with short (less than 30 minutes) first febrile convulsions were studied between 3 and 22 hours after convulsive episodes. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured. Biochemical signs of cerebral hypoxia were found in only 2 patients, one of whom had short, repeated convulsions. Our findings indicate that hypoxic damage is unlikely to result from a short-duration febrile convulsion.", "contents": "Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after short (less than 30 minutes) first febrile convulsions in children. Twenty-nine infants and children with short (less than 30 minutes) first febrile convulsions were studied between 3 and 22 hours after convulsive episodes. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured. Biochemical signs of cerebral hypoxia were found in only 2 patients, one of whom had short, repeated convulsions. Our findings indicate that hypoxic damage is unlikely to result from a short-duration febrile convulsion."}
{"id": "PMID:23078", "title": "Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after convulsions of varied duration and aetiology in children.", "content": "Twenty-two infants and children were studied after convulsions of varied cause and duration. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured between 3 and 18 hours after convulsive episodes. Biochemical signs of cerebral hypoxia were found in 7 patients with prolonged (greater than 30 minutes) or recurrent short convulsions. These signs were absent in patients with single short convulsions. These findings indicate that cerebral hypoxia and possible brain damage is a hazard of prolonged or rapidly recurring short convulsions.", "contents": "Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after convulsions of varied duration and aetiology in children. Twenty-two infants and children were studied after convulsions of varied cause and duration. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured between 3 and 18 hours after convulsive episodes. Biochemical signs of cerebral hypoxia were found in 7 patients with prolonged (greater than 30 minutes) or recurrent short convulsions. These signs were absent in patients with single short convulsions. These findings indicate that cerebral hypoxia and possible brain damage is a hazard of prolonged or rapidly recurring short convulsions."}
{"id": "PMID:23079", "title": "Hemodynamic effects of prolonged hyperoxia.", "content": "Experimental studies have consistently demonstrated the development of perivascular edema in the dog lung following prolonged exposure to 95% oxygen. This pathological change has been thought to result from capillary injury, but a direct effect secondary to left ventricular dysfunction has not yet been excluded. To evaluate the latter possibility, ten trained, awake dogs were prepared with monitoring of right and left atrial, systemic and pulmonary artery pressures, cardiac output, and mixed venous and arterial blood gases. Animals were exposed to an F1O2 greater than 0.95 for 48-70 hours. Radioactive 8-10 mu microspheres (141Ce, 51Cr, 85Sr, 46Sc) were injected into the left atrium at zero, six, 24, and 48 hours. PaO2 was 480 +/- 10 mm Hg during exposure, and the pulmonary shunt fraction increased from 11.3% to 16.9% (p less than 0.0001) during 70 hours. Left atrial pressure fell from 9 +/- 2 mm Hg to 3 +/- 3 mm Hg (p less than 0.0001), but cardiac output was constant at 2.7 +/- 0.1 l/min. Pulmonary arteriolar resistance increased from 183 +/- 20 dynes-sec-CM-5 to 791 +/- 30 at 70 hours (p less than 0.0001). Histologic sections of the lungs demonstrated the characteristic perivascular edema. Of particular interest was the fact that myocardial perfusion was significantly increased to all three layers of the ventricular wall at 24 and 48 hours. These data indicate that perivascular edema developing after exposure to high concentrations of oxygen is secondary to pulmonary capillary endothelial damage with no evidence that myocardial dysfunction occurs during this period.", "contents": "Hemodynamic effects of prolonged hyperoxia. Experimental studies have consistently demonstrated the development of perivascular edema in the dog lung following prolonged exposure to 95% oxygen. This pathological change has been thought to result from capillary injury, but a direct effect secondary to left ventricular dysfunction has not yet been excluded. To evaluate the latter possibility, ten trained, awake dogs were prepared with monitoring of right and left atrial, systemic and pulmonary artery pressures, cardiac output, and mixed venous and arterial blood gases. Animals were exposed to an F1O2 greater than 0.95 for 48-70 hours. Radioactive 8-10 mu microspheres (141Ce, 51Cr, 85Sr, 46Sc) were injected into the left atrium at zero, six, 24, and 48 hours. PaO2 was 480 +/- 10 mm Hg during exposure, and the pulmonary shunt fraction increased from 11.3% to 16.9% (p less than 0.0001) during 70 hours. Left atrial pressure fell from 9 +/- 2 mm Hg to 3 +/- 3 mm Hg (p less than 0.0001), but cardiac output was constant at 2.7 +/- 0.1 l/min. Pulmonary arteriolar resistance increased from 183 +/- 20 dynes-sec-CM-5 to 791 +/- 30 at 70 hours (p less than 0.0001). Histologic sections of the lungs demonstrated the characteristic perivascular edema. Of particular interest was the fact that myocardial perfusion was significantly increased to all three layers of the ventricular wall at 24 and 48 hours. These data indicate that perivascular edema developing after exposure to high concentrations of oxygen is secondary to pulmonary capillary endothelial damage with no evidence that myocardial dysfunction occurs during this period."}
{"id": "PMID:23081", "title": "Is a left ventricular vent necessary during cardiopulmonary bypass?", "content": "This study evaluated the coronary flow and the internal diameter, pressure, and metabolism of the left ventricle using four different cardiopulmonary bypass techniques. Conditioned dogs underwent a 30-minute stabilizing period on cardiopulmonary bypass with a beating, empty heart (normothermia and a flow of 80 ml/kg/min). They were then fibrillated and subjected to four experiments: Group A (7 dogs)--left ventricular vent, caval tapes open; group B (7 dogs)--left ventricular vent, caval tapes closed; group C (7 dogs)--no vent, caval tapes open; group D (4 dogs)--no vent, caval tapes closed. There was no major difference in any of these variables among Groups A and B (both ventricles vented). Group D (no vent, tapes closed) had significantly increased wall tension, decreased coronary flow, decreased subendocardiac flow, and ischemia. In contrast, Group C dogs (no vent, tapes open) had only a slight increase in left ventricular diameter and pressure, with no change from Group A and B dogs in coronary flow, lactate extraction, hydrogen ion production, or potassium difference. Therefore, venting the fibrillating ventricle, either with or without snaring of the caval tapes, is probably the best method to use during the distal anastomosis in a coronary artery bypass operation. However, if a vent is not used, the caval tapes should be left open to allow complete diversion of the venous blood and decompression of the left ventricle.", "contents": "Is a left ventricular vent necessary during cardiopulmonary bypass? This study evaluated the coronary flow and the internal diameter, pressure, and metabolism of the left ventricle using four different cardiopulmonary bypass techniques. Conditioned dogs underwent a 30-minute stabilizing period on cardiopulmonary bypass with a beating, empty heart (normothermia and a flow of 80 ml/kg/min). They were then fibrillated and subjected to four experiments: Group A (7 dogs)--left ventricular vent, caval tapes open; group B (7 dogs)--left ventricular vent, caval tapes closed; group C (7 dogs)--no vent, caval tapes open; group D (4 dogs)--no vent, caval tapes closed. There was no major difference in any of these variables among Groups A and B (both ventricles vented). Group D (no vent, tapes closed) had significantly increased wall tension, decreased coronary flow, decreased subendocardiac flow, and ischemia. In contrast, Group C dogs (no vent, tapes open) had only a slight increase in left ventricular diameter and pressure, with no change from Group A and B dogs in coronary flow, lactate extraction, hydrogen ion production, or potassium difference. Therefore, venting the fibrillating ventricle, either with or without snaring of the caval tapes, is probably the best method to use during the distal anastomosis in a coronary artery bypass operation. However, if a vent is not used, the caval tapes should be left open to allow complete diversion of the venous blood and decompression of the left ventricle."}
{"id": "PMID:23082", "title": "Effect of some beta-adrenergic blocking drugs on the renal bloow flow in dogs.", "content": "Using timed collection of blood returning via the renal veins, the renal blood flow was determined in anaesthetized dogs, following the intravenous injection of 3 beta-adrenergic blockers, namely propranolol, oxprenolol and pindolol. The test drugs were given as a bolus or as an infusion, and their effects on the renal blood flow and blood pressure were studied. All the test drugs produced diminution in both the renal blood flow and blood pressure. However, these effects were variable in degree. The diminution in the renal blood flow under the influence of beta-adrenergic blockers might be explained by concomitant reduction in the cardiac output and/or blockade of the renal vasodilator beta-adrenergic receptors. An added factor might by sympathetic stimulation with consequent renal vasoconstriction in the case of blockers with intrinsic sympathomimetic activity. Beta-adrenergic blocking drugs should be given with extreme caution in cases with impaired renal function.", "contents": "Effect of some beta-adrenergic blocking drugs on the renal bloow flow in dogs. Using timed collection of blood returning via the renal veins, the renal blood flow was determined in anaesthetized dogs, following the intravenous injection of 3 beta-adrenergic blockers, namely propranolol, oxprenolol and pindolol. The test drugs were given as a bolus or as an infusion, and their effects on the renal blood flow and blood pressure were studied. All the test drugs produced diminution in both the renal blood flow and blood pressure. However, these effects were variable in degree. The diminution in the renal blood flow under the influence of beta-adrenergic blockers might be explained by concomitant reduction in the cardiac output and/or blockade of the renal vasodilator beta-adrenergic receptors. An added factor might by sympathetic stimulation with consequent renal vasoconstriction in the case of blockers with intrinsic sympathomimetic activity. Beta-adrenergic blocking drugs should be given with extreme caution in cases with impaired renal function."}
{"id": "PMID:23083", "title": "Transmitter mobilization at the frog neuromuscular junction.", "content": "During frequency facilitation of frog neuromuscular junctions depressed by Mg++, the relationship between quantal content (m) and frequency of stimulation (0.5 to 8 Hz) is exponential. The slope of the relationship (k) reflects transmitter mobilization and the zero-frequency intercept (mo) reflects the basic release process. The catecholamines, tetraethylammonium, guanidine and raised [Ca++]o increased mo but had no effect on k. At junctions where release ranged from 200 to 500 quanta sec-1 during steady-state conditions, this result was interpreted to mean that the drugs increased both transmitter release and mobilization. An analog of hemicholinium-3, DMAE, depressed k, reflecting the ability of DMAE to depress transmitter mobilization. The alternative possibility that the frequency facilitation relationship was altered by effects of the drugs on the number of activated release sites was also considered.", "contents": "Transmitter mobilization at the frog neuromuscular junction. During frequency facilitation of frog neuromuscular junctions depressed by Mg++, the relationship between quantal content (m) and frequency of stimulation (0.5 to 8 Hz) is exponential. The slope of the relationship (k) reflects transmitter mobilization and the zero-frequency intercept (mo) reflects the basic release process. The catecholamines, tetraethylammonium, guanidine and raised [Ca++]o increased mo but had no effect on k. At junctions where release ranged from 200 to 500 quanta sec-1 during steady-state conditions, this result was interpreted to mean that the drugs increased both transmitter release and mobilization. An analog of hemicholinium-3, DMAE, depressed k, reflecting the ability of DMAE to depress transmitter mobilization. The alternative possibility that the frequency facilitation relationship was altered by effects of the drugs on the number of activated release sites was also considered."}
{"id": "PMID:23084", "title": "Further evidence for GABA-ergic mechanisms in the action of benzodiazepines.", "content": "Drugs of the benzodiazepine series (clonazepam, lorazepam, diazepam and medazepam) increase the inhibitory processes in the cerebral cortex as it has been shown by means of the recovery cycles of the intracortical response. There is a correlation between the effect on the recovery cycles and their protective action against convulsions induced by GABA deficit. Diazepam enhances the inhibitory effect of GABA applied iontophoretically to rabbit sensorymotor cortex neurons. The drug GABA-ergic effect seems to be specific since it fails to modify the effects of other putative neurotransmitters (glutamate, glycine, acetylcholine). The alteration of rat conflict situation behaviour under diazepam has been eliminated due to the blockade of GABA-receptors by gicuculline and the decrease of the GABA level by thiosemicarbazide. It is inferred that the main effects of benzodiazepines are mediated by GABA and suggested that these agents increase the sensitivity of postsynaptic GABA-ergic receptors.", "contents": "Further evidence for GABA-ergic mechanisms in the action of benzodiazepines. Drugs of the benzodiazepine series (clonazepam, lorazepam, diazepam and medazepam) increase the inhibitory processes in the cerebral cortex as it has been shown by means of the recovery cycles of the intracortical response. There is a correlation between the effect on the recovery cycles and their protective action against convulsions induced by GABA deficit. Diazepam enhances the inhibitory effect of GABA applied iontophoretically to rabbit sensorymotor cortex neurons. The drug GABA-ergic effect seems to be specific since it fails to modify the effects of other putative neurotransmitters (glutamate, glycine, acetylcholine). The alteration of rat conflict situation behaviour under diazepam has been eliminated due to the blockade of GABA-receptors by gicuculline and the decrease of the GABA level by thiosemicarbazide. It is inferred that the main effects of benzodiazepines are mediated by GABA and suggested that these agents increase the sensitivity of postsynaptic GABA-ergic receptors."}
{"id": "PMID:23085", "title": "Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. II. Solubilization of the membrane-bound component.", "content": "The Rhodospirillum rubrum pyridine dinucleotide transhydrogenase system is comprised of a membrane-bound component and an easily dissociable soluble factor. Active transhydrogenase complex was solubilized by extraction of chromatophores with lysolecithin. The membrane component was also extracted from membranes depleted of soluble factor. The solubilized membrane component reconstituted transhydrogenase activity upon addition of soluble factor. Various other ionic and non-ionic detergents, including Triton X-100, Lubrol WX, deoxycholate, and digitonin, were ineffectual for solubilization and/or inhibited the enzyme at higher concentrations. The solubilized membrane component was significantly less thermal stable than the membrane-bound component. None of the pyridine dinucleotide substrate affected the thermostability of the solubilized membrane-bound component, whereas NADP+ and NADPH afforded protection to membrane-bound component. NADPH stimulated trypsin inactivation of membrane-bound component to a greater extent that NADP+, but inactivation of solubilized membrane component was stimulated to the same extent by both pyridine dinucleotides. The solubilized membrane component appears to have a slightly higher affinity for soluble factor than does the membrane-bound component.", "contents": "Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. II. Solubilization of the membrane-bound component. The Rhodospirillum rubrum pyridine dinucleotide transhydrogenase system is comprised of a membrane-bound component and an easily dissociable soluble factor. Active transhydrogenase complex was solubilized by extraction of chromatophores with lysolecithin. The membrane component was also extracted from membranes depleted of soluble factor. The solubilized membrane component reconstituted transhydrogenase activity upon addition of soluble factor. Various other ionic and non-ionic detergents, including Triton X-100, Lubrol WX, deoxycholate, and digitonin, were ineffectual for solubilization and/or inhibited the enzyme at higher concentrations. The solubilized membrane component was significantly less thermal stable than the membrane-bound component. None of the pyridine dinucleotide substrate affected the thermostability of the solubilized membrane-bound component, whereas NADP+ and NADPH afforded protection to membrane-bound component. NADPH stimulated trypsin inactivation of membrane-bound component to a greater extent that NADP+, but inactivation of solubilized membrane component was stimulated to the same extent by both pyridine dinucleotides. The solubilized membrane component appears to have a slightly higher affinity for soluble factor than does the membrane-bound component."}
{"id": "PMID:23086", "title": "Influence of inorganic phosphate and organic buffers on cephalosporin production by Streptomyces clavuligerus.", "content": "A high concentration of potassium phosphate (75--100 mM) stabilized pH and supported extensive growth of Streptomyces clavuligerus in a chemically defined medium; such a concentration also inhibited cephalosporin production. Although Tris buffer was found to have detrimental effects on growth and antibiotic production, 3-(N-morpholine)-propane sulfonate (MOPS) or 2-(NP-morpholine)-ethane sulfonate (MES) buffer provided a nontoxic buffering system. In the presence of MOPS buffer, cephalosporin production was optimal at 25 mM phosphate, whereas higher concentrations of phosphate progressively inhibited antibiotic production up to 85% without modifying the pH pattern. MOPS buffer can be used to conduct fermentations at a relatively constant pH value in shake flasks.", "contents": "Influence of inorganic phosphate and organic buffers on cephalosporin production by Streptomyces clavuligerus. A high concentration of potassium phosphate (75--100 mM) stabilized pH and supported extensive growth of Streptomyces clavuligerus in a chemically defined medium; such a concentration also inhibited cephalosporin production. Although Tris buffer was found to have detrimental effects on growth and antibiotic production, 3-(N-morpholine)-propane sulfonate (MOPS) or 2-(NP-morpholine)-ethane sulfonate (MES) buffer provided a nontoxic buffering system. In the presence of MOPS buffer, cephalosporin production was optimal at 25 mM phosphate, whereas higher concentrations of phosphate progressively inhibited antibiotic production up to 85% without modifying the pH pattern. MOPS buffer can be used to conduct fermentations at a relatively constant pH value in shake flasks."}
{"id": "PMID:23087", "title": "Prolactin responses to neuroleptics in normal and schizophrenic subjects.", "content": "The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies.", "contents": "Prolactin responses to neuroleptics in normal and schizophrenic subjects. The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies."}
{"id": "PMID:23088", "title": "The interferonogenic agent tilorone as a modulator of GvH reaction in mice.", "content": "The effects of tilorone hydrochloride (TH), a powerful interferongenic agent exhibiting also immune modulatory properties on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at days-4 or-2 induced an enhanced GvH reactivity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, the latter of which are responsible for induction of GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested.", "contents": "The interferonogenic agent tilorone as a modulator of GvH reaction in mice. The effects of tilorone hydrochloride (TH), a powerful interferongenic agent exhibiting also immune modulatory properties on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at days-4 or-2 induced an enhanced GvH reactivity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, the latter of which are responsible for induction of GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested."}
{"id": "PMID:23091", "title": "Physiological basis of salt tolerance in plants.", "content": "For most plants, and under most field conditions, osmotic effects of salinity greatly predominate in restricting growth and yields. In certain cases, however, specific ion effects may be decisive. These may involve either nutrition, as in calcium deficiency in some lettuce varieties, tomato, and bell peppers, or direct toxicity (chloride or sodium toxicity, or both) in tree and vine crops. Rootstocks, or varieties that restrict the uptake of toxic ions, increase the salt tolerance of some susceptible fruit crops. Salinity-induced nutritional imbalance can, in some cases, be corrected by selecting better adapted varieties and in others by the use of foliar nutrient sprays. Recent evidence indicates simple single-gene control over uptakes of chloride and sodium, but the more general osmotic effects appear to be complex and under multigenic control.", "contents": "Physiological basis of salt tolerance in plants. For most plants, and under most field conditions, osmotic effects of salinity greatly predominate in restricting growth and yields. In certain cases, however, specific ion effects may be decisive. These may involve either nutrition, as in calcium deficiency in some lettuce varieties, tomato, and bell peppers, or direct toxicity (chloride or sodium toxicity, or both) in tree and vine crops. Rootstocks, or varieties that restrict the uptake of toxic ions, increase the salt tolerance of some susceptible fruit crops. Salinity-induced nutritional imbalance can, in some cases, be corrected by selecting better adapted varieties and in others by the use of foliar nutrient sprays. Recent evidence indicates simple single-gene control over uptakes of chloride and sodium, but the more general osmotic effects appear to be complex and under multigenic control."}
{"id": "PMID:23100", "title": "Characteristics and postnatal development of the acid lipase activity of the rat small intestine.", "content": "Acid lipase was identified in the rat small intestine by using esters of 4-methylumbelliferone as substrates. Maximum activity towards the oleate ester was found at pH 4.0. In adult animals, the activity of acid lipase exhibited both latency and sedimentability, indicating a lyosomal localization. The activity of acid lipase was practically the same along the height of the villus, thus paralleling the distribution of acid beta-galactosidase. In adult rats, the activity of acid lipase in proximal (jejunum) and middle (mid-jejunum) sections of the small intestine was practically the same and exceeded the activity in the distal (ileum) section by a factor of 2. In suckling rats, the activity of the enzyme in the mid-jejunum exceeded that in the jejunum and ileum by 2.5- and 1.5-fold respectively. During postnatal development, the acid lipase activity of the mid-jejunum showed a peak between days 10 and 15, at which time it exceeded the adult mid-jejunum activity by 5--6-fold.", "contents": "Characteristics and postnatal development of the acid lipase activity of the rat small intestine. Acid lipase was identified in the rat small intestine by using esters of 4-methylumbelliferone as substrates. Maximum activity towards the oleate ester was found at pH 4.0. In adult animals, the activity of acid lipase exhibited both latency and sedimentability, indicating a lyosomal localization. The activity of acid lipase was practically the same along the height of the villus, thus paralleling the distribution of acid beta-galactosidase. In adult rats, the activity of acid lipase in proximal (jejunum) and middle (mid-jejunum) sections of the small intestine was practically the same and exceeded the activity in the distal (ileum) section by a factor of 2. In suckling rats, the activity of the enzyme in the mid-jejunum exceeded that in the jejunum and ileum by 2.5- and 1.5-fold respectively. During postnatal development, the acid lipase activity of the mid-jejunum showed a peak between days 10 and 15, at which time it exceeded the adult mid-jejunum activity by 5--6-fold."}
{"id": "PMID:23101", "title": "Biosynthesis of acetyl-coenzyme A in the electric organ of Torpedo marmorata in relation to acetylcholine metabolism.", "content": "Formation of acetyl-CoA through acetyl-CoA synthetase (forward reaction) and through choline acyltransferase (backward reaction) was investigated in tissue extract from the electric organ of Torpedo marmorata. When the tissue extract was submitted to gel filtration on Sephadex G-25, the formation of acetyl-CoA by acetyl-CoA synthetase appeared fully dependent on ATP and CoA and partially dependent on acetate (an endogenous supply of acetate is discussed). Choline acetyltransferase was a potent source of acetyl-CoA, only requiring acetylcholine and CoA, and was much more efficient than acetyl-CoA synthetase for concentrations of acetylcholine likely to be present in nerve endings.", "contents": "Biosynthesis of acetyl-coenzyme A in the electric organ of Torpedo marmorata in relation to acetylcholine metabolism. Formation of acetyl-CoA through acetyl-CoA synthetase (forward reaction) and through choline acyltransferase (backward reaction) was investigated in tissue extract from the electric organ of Torpedo marmorata. When the tissue extract was submitted to gel filtration on Sephadex G-25, the formation of acetyl-CoA by acetyl-CoA synthetase appeared fully dependent on ATP and CoA and partially dependent on acetate (an endogenous supply of acetate is discussed). Choline acetyltransferase was a potent source of acetyl-CoA, only requiring acetylcholine and CoA, and was much more efficient than acetyl-CoA synthetase for concentrations of acetylcholine likely to be present in nerve endings."}
{"id": "PMID:23102", "title": "Growth of liver accompanied by an increased binding of aminoacyl-transfer ribonucleic acids.", "content": "Homogenates of rat liver obtained 3 or 14 days after partial hepatectomy were used to prepare the postmicrosomal pH5-supernatant fraction and to prepare salt-wash fractions of the 40S ribosomal subunits and the 80S ribosomes. The factor-dependent binding of methionyl-tRNAfMet to ribosomes and the elongation-factor-1-dependent binding of phenylalanyl-tRNA to ribosomes were both increased after 3 days of growth, but not after 14 days of growth. An activity inhibitory to phenylalanyl-tRNA binding that was located in ribosomal wash fractions was decreased after 14 days of growth. Since the decreased inhibitory activity was obtained from the ribosomes and was tested against ribosomes and excess of pH5-supernatant fraction from control rat liver, its action was separate from the phenylalanyl-tRNA binding activities of the pH5-supernatant fractions from sham-operated and regenerating liver.", "contents": "Growth of liver accompanied by an increased binding of aminoacyl-transfer ribonucleic acids. Homogenates of rat liver obtained 3 or 14 days after partial hepatectomy were used to prepare the postmicrosomal pH5-supernatant fraction and to prepare salt-wash fractions of the 40S ribosomal subunits and the 80S ribosomes. The factor-dependent binding of methionyl-tRNAfMet to ribosomes and the elongation-factor-1-dependent binding of phenylalanyl-tRNA to ribosomes were both increased after 3 days of growth, but not after 14 days of growth. An activity inhibitory to phenylalanyl-tRNA binding that was located in ribosomal wash fractions was decreased after 14 days of growth. Since the decreased inhibitory activity was obtained from the ribosomes and was tested against ribosomes and excess of pH5-supernatant fraction from control rat liver, its action was separate from the phenylalanyl-tRNA binding activities of the pH5-supernatant fractions from sham-operated and regenerating liver."}
{"id": "PMID:23103", "title": "Transport and oxidation of choline by liver mitochondria.", "content": "1. Rapid choline oxidation and the onset of P(i)-induced swelling by liver mitochondria, incubated in a sucrose medium at or above pH7.0, required the addition of both P(i) and an uncoupling agent. Below pH7.0, P(i) alone was required for rapid choline oxidation and swelling. 2. Choline oxidation was inhibited by each of several reagents that also inhibited P(i)-induced swelling under similar conditions of incubation, including EGTA, mersalyl, Mg(2+), the Ca(2+)-ionophore A23187, rotenone and nupercaine. None of these reagents had any significant effect on the rate of choline oxidation by sonicated mitochondria. There was therefore a close correlation between the conditions required for rapid choline oxidation and for P(i)-induced swelling to occur, suggesting that in the absence of mitochondrial swelling the rate of choline oxidation is regulated by the rate of choline transport across the mitochondrial membrane. 3. Respiratory-chain inhibitors, uncoupling agents (at pH6.5) and ionophore A23187 caused a loss of endogenous Ca(2+) from mitochondria, whereas nupercaine and Mg(2+) had no significant effect on the Ca(2+) content. Inhibition of choline oxidation and mitochondrial swelling by ionophore A23187 was reversed by adding Ca(2+), but not by Mg(2+). It is concluded that added P(i) promotes the Ca(2+)-dependent activation of mitochondrial membrane phospholipase activity in respiring mitochondria, causing an increase in the permeability of the mitochondrial inner membrane to choline and therefore enabling rapid choline oxidation to occur. Nupercaine and Mg(2+) appear to block choline oxidation and swelling by inhibiting phospholipase activity. 4. Choline was oxidized slowly by tightly coupled mitochondria largely depleted of their endogenous adenine nucleotides, suggesting that these compounds are not directly concerned in the regulation of choline oxidation. 5. The results are discussed in relation to the possible mechanism of choline transport across the mitochondrial membrane in vivo and the influence of this process on the pathways of choline metabolism in the liver.", "contents": "Transport and oxidation of choline by liver mitochondria. 1. Rapid choline oxidation and the onset of P(i)-induced swelling by liver mitochondria, incubated in a sucrose medium at or above pH7.0, required the addition of both P(i) and an uncoupling agent. Below pH7.0, P(i) alone was required for rapid choline oxidation and swelling. 2. Choline oxidation was inhibited by each of several reagents that also inhibited P(i)-induced swelling under similar conditions of incubation, including EGTA, mersalyl, Mg(2+), the Ca(2+)-ionophore A23187, rotenone and nupercaine. None of these reagents had any significant effect on the rate of choline oxidation by sonicated mitochondria. There was therefore a close correlation between the conditions required for rapid choline oxidation and for P(i)-induced swelling to occur, suggesting that in the absence of mitochondrial swelling the rate of choline oxidation is regulated by the rate of choline transport across the mitochondrial membrane. 3. Respiratory-chain inhibitors, uncoupling agents (at pH6.5) and ionophore A23187 caused a loss of endogenous Ca(2+) from mitochondria, whereas nupercaine and Mg(2+) had no significant effect on the Ca(2+) content. Inhibition of choline oxidation and mitochondrial swelling by ionophore A23187 was reversed by adding Ca(2+), but not by Mg(2+). It is concluded that added P(i) promotes the Ca(2+)-dependent activation of mitochondrial membrane phospholipase activity in respiring mitochondria, causing an increase in the permeability of the mitochondrial inner membrane to choline and therefore enabling rapid choline oxidation to occur. Nupercaine and Mg(2+) appear to block choline oxidation and swelling by inhibiting phospholipase activity. 4. Choline was oxidized slowly by tightly coupled mitochondria largely depleted of their endogenous adenine nucleotides, suggesting that these compounds are not directly concerned in the regulation of choline oxidation. 5. The results are discussed in relation to the possible mechanism of choline transport across the mitochondrial membrane in vivo and the influence of this process on the pathways of choline metabolism in the liver."}
{"id": "PMID:23104", "title": "Alterations in nicotinamide and adenine nucleotide systems during mixed-function oxidation of p-nitroanisole in perfused livers from normal and phenobarbital-treated rats.", "content": "The contents of adenine nucleotides as well as steady-state concentrations of a number of glycolytic, pentose phosphate-pathway and tricarboxylic acid-cycle intermediates were measured in extracts of livers from normal and phenobarbital-treated rats that were perfused with p-nitroanisole. Metabolites were measured in livers that were freeze-clamped during periods of maximal rates of drug metabolism. Treatment of rats with phenobarbital increased rates of p-nitroanisole O-demethylation approx. fivefold. The concentrations of lactate, xylulose 5-phosphate and ribulose 5-phosphate were increased by phenobarbital treatment, whereas that of fructose 1,6-bisphosphate declined. Perfusion of livers with p-nitroanisole produced significant increases in 6-phosphogluconate and ribulose 5-phosphate in livers from phenobarbital-treated rats, but not in livers from control rats. Treatment of rats with phenobarbital caused [NADP(+)]/[NADPH] to change in the direction of more oxidation, as calculated from measured concentrations of 6-phosphogluconate and ribulose 5-phosphate; however, the [NADP(+)]/[NADPH] ratio calculated from ;malic' enzyme was not changed. Additions of p-nitroanisole produced a reduction of NADP(+) as calculated from 6-phosphogluconate dehydrogenase activity, but did not alter the [NADP(+)]/[NADPH] ratio calculated from substrates assumed to be in equilibrium with ;malic' enzyme. Activities of both glucose 6-phosphate dehydrogenase and ;malic' enzyme were increased by phenobarbital treatment. NAD(+) became more reduced as a result of phenobarbital treatment; however, perfusion of livers with p-nitroanisole did not cause a change in the oxidation-reduction state of this nucleotide. Concentrations of adenine nucleotides in livers were not altered significantly by treatment of rats with phenobarbital; however, a significant decline in the [ATP]/[ADP] ratio occurred during mixed-function oxidation of p-nitroanisole in livers from phenobarbital-treated rats, but not in livers from normal rats. Perfusion of livers with two other substrates for mixed-function oxidation, hexobarbital and aminopyrine, produced an increase in the [NADP(+)]/[NADPH] ratio calculated from ;malic' enzyme. In contrast with livers perfused with p-nitroanisole, there was no significant change in adenine nucleotides in livers exposed to hexobarbital or aminopyrine. Addition of 2,4-dinitrophenol (25mum) to the perfusate containing aminopyrine decreased the [ATP]/[ADP] ratio and tended to prevent the oxidation of NADPH observed with aminopyrine alone. Thus in the presence of an uncoupler of oxidative phosphorylation, NADPH generation may exceed its utilization via mixed-function oxidation.", "contents": "Alterations in nicotinamide and adenine nucleotide systems during mixed-function oxidation of p-nitroanisole in perfused livers from normal and phenobarbital-treated rats. The contents of adenine nucleotides as well as steady-state concentrations of a number of glycolytic, pentose phosphate-pathway and tricarboxylic acid-cycle intermediates were measured in extracts of livers from normal and phenobarbital-treated rats that were perfused with p-nitroanisole. Metabolites were measured in livers that were freeze-clamped during periods of maximal rates of drug metabolism. Treatment of rats with phenobarbital increased rates of p-nitroanisole O-demethylation approx. fivefold. The concentrations of lactate, xylulose 5-phosphate and ribulose 5-phosphate were increased by phenobarbital treatment, whereas that of fructose 1,6-bisphosphate declined. Perfusion of livers with p-nitroanisole produced significant increases in 6-phosphogluconate and ribulose 5-phosphate in livers from phenobarbital-treated rats, but not in livers from control rats. Treatment of rats with phenobarbital caused [NADP(+)]/[NADPH] to change in the direction of more oxidation, as calculated from measured concentrations of 6-phosphogluconate and ribulose 5-phosphate; however, the [NADP(+)]/[NADPH] ratio calculated from ;malic' enzyme was not changed. Additions of p-nitroanisole produced a reduction of NADP(+) as calculated from 6-phosphogluconate dehydrogenase activity, but did not alter the [NADP(+)]/[NADPH] ratio calculated from substrates assumed to be in equilibrium with ;malic' enzyme. Activities of both glucose 6-phosphate dehydrogenase and ;malic' enzyme were increased by phenobarbital treatment. NAD(+) became more reduced as a result of phenobarbital treatment; however, perfusion of livers with p-nitroanisole did not cause a change in the oxidation-reduction state of this nucleotide. Concentrations of adenine nucleotides in livers were not altered significantly by treatment of rats with phenobarbital; however, a significant decline in the [ATP]/[ADP] ratio occurred during mixed-function oxidation of p-nitroanisole in livers from phenobarbital-treated rats, but not in livers from normal rats. Perfusion of livers with two other substrates for mixed-function oxidation, hexobarbital and aminopyrine, produced an increase in the [NADP(+)]/[NADPH] ratio calculated from ;malic' enzyme. In contrast with livers perfused with p-nitroanisole, there was no significant change in adenine nucleotides in livers exposed to hexobarbital or aminopyrine. Addition of 2,4-dinitrophenol (25mum) to the perfusate containing aminopyrine decreased the [ATP]/[ADP] ratio and tended to prevent the oxidation of NADPH observed with aminopyrine alone. Thus in the presence of an uncoupler of oxidative phosphorylation, NADPH generation may exceed its utilization via mixed-function oxidation."}
{"id": "PMID:23105", "title": "Influence of cations at the plasma membrane in controlling polysaccharide secretion from sycamore suspension cells.", "content": "1. Three soluble polysaccharides and a soluble protein containing hydroxyproline were secreted by sycamore suspension cultures. l-[1-(3)H]Fucose was incorporated solely into the fucose of fucoxyloglucan and l-[1-(14)C]arabinose mainly into the arabinose of arabino-galactan. [U-(14)C]Glucose was a general precursor for soluble protein and polysaccharides. 2. The steady-state rate of secretion of all the polymers was increased within seconds of adding various electrolytes and polyelectrolytes to the growth medium. The increased secretion was induced by cations at the outer surface of the plasma membrane. It was brought about by a stimulation of the normal mechanisms of cell-wall polysaccharide secretion. It was partly inhibited by anaerobiosis or sodium arsenate and was unaffected by temperature changes in the range 0-35 degrees C. 3. The precursor pool from which secretion was induced contained completely synthesized polysaccharides and was probably located in the Golgi-derived vesicles. The results indicated that the endoplasmic reticulum did not secrete polysaccharide directly to the cell exterior. 4. The various cations probably induced secretion by causing a depolarization of the negative electric potential of the cell surface, and this resulted in the fusion of vesicles with the plasma membrane. 5. Analogy with exocytosis and pinocytosis in various animal tissues suggested that the decreased surface potential brought about membrane fusion by causing an increase in plasma-membrane permeability to Ca(2+). 6. The results showed that the fusion of vesicles with the plasma membrane was rate-limiting and a potential control point. Auxin-stimulated cell-wall deposition could be a result of a stimulated influx of Ca(2+) causing vesicle fusion with the plasma membrane.", "contents": "Influence of cations at the plasma membrane in controlling polysaccharide secretion from sycamore suspension cells. 1. Three soluble polysaccharides and a soluble protein containing hydroxyproline were secreted by sycamore suspension cultures. l-[1-(3)H]Fucose was incorporated solely into the fucose of fucoxyloglucan and l-[1-(14)C]arabinose mainly into the arabinose of arabino-galactan. [U-(14)C]Glucose was a general precursor for soluble protein and polysaccharides. 2. The steady-state rate of secretion of all the polymers was increased within seconds of adding various electrolytes and polyelectrolytes to the growth medium. The increased secretion was induced by cations at the outer surface of the plasma membrane. It was brought about by a stimulation of the normal mechanisms of cell-wall polysaccharide secretion. It was partly inhibited by anaerobiosis or sodium arsenate and was unaffected by temperature changes in the range 0-35 degrees C. 3. The precursor pool from which secretion was induced contained completely synthesized polysaccharides and was probably located in the Golgi-derived vesicles. The results indicated that the endoplasmic reticulum did not secrete polysaccharide directly to the cell exterior. 4. The various cations probably induced secretion by causing a depolarization of the negative electric potential of the cell surface, and this resulted in the fusion of vesicles with the plasma membrane. 5. Analogy with exocytosis and pinocytosis in various animal tissues suggested that the decreased surface potential brought about membrane fusion by causing an increase in plasma-membrane permeability to Ca(2+). 6. The results showed that the fusion of vesicles with the plasma membrane was rate-limiting and a potential control point. Auxin-stimulated cell-wall deposition could be a result of a stimulated influx of Ca(2+) causing vesicle fusion with the plasma membrane."}
{"id": "PMID:23106", "title": "Evidence that fatty acid synthesis in the interscapular brown adipose tissue of cold-adapted rats is increased in vivo by insulin by mechanisms involving parallel activation of pyruvate dehydrogenase and acetyl-coenzyme A carboxylase.", "content": "Plasma insulin concentrations in cold-adapted rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in interscapular brown adipose tissue were determined from the incorporation of 3H from 3H2O into tissue lipid. Rates of synthesis were greatly elevated after glucose administration and markedly decreased after injection with anti-insulin serum. Parallel changes in the initial activities of both acetyl-CoA carboxylase and pyruvate dehydrogenase were observed under these conditions, but no changes in total activities were evident. The results suggest that this tissue is an important site of fatty acid synthesis in the cold-adapted rat and that this feature of the tissue is sensitive to changes in plasma insulin concentrations.", "contents": "Evidence that fatty acid synthesis in the interscapular brown adipose tissue of cold-adapted rats is increased in vivo by insulin by mechanisms involving parallel activation of pyruvate dehydrogenase and acetyl-coenzyme A carboxylase. Plasma insulin concentrations in cold-adapted rats were altered acutely by administration of glucose or anti-insulin serum. Rates of fatty acid synthesis in interscapular brown adipose tissue were determined from the incorporation of 3H from 3H2O into tissue lipid. Rates of synthesis were greatly elevated after glucose administration and markedly decreased after injection with anti-insulin serum. Parallel changes in the initial activities of both acetyl-CoA carboxylase and pyruvate dehydrogenase were observed under these conditions, but no changes in total activities were evident. The results suggest that this tissue is an important site of fatty acid synthesis in the cold-adapted rat and that this feature of the tissue is sensitive to changes in plasma insulin concentrations."}
{"id": "PMID:23107", "title": "Characterization and serology of the matrix protein from a nuclear-polyhedrosis virus of Trichoplusia ni before and after degradation by an endogenous proteinase.", "content": "The intact matrix protein from a nuclear-polyhedrosis virus of the cabbage looper (Trichoplusia ni), isolated after inhibition of an endogenous serine-type proteinase, was further purified by molecular-sieve chromatography. The matrix protein was associated with carbohydrate moieties, and the carbohydrate content was determined for the two major peptides isolated after proteolysis by the endogenous proteinase. The association-dissociation interactions of the intact and proteinase-hydrolysed monomer units were characterized at high and low pH. At pH1.9, proteinase-degraded matrix protein dissociated into two different peptide fractions, FI and FII. Fraction FII, a single peptide of 9400 daltons, comprised one-third of the monomer unit of 28 000 daltons. At pH9.5, the degraded peptides were tightly associated in units equivalent to the intact monomer. These monomer equivalents associated to form a series of interconverting aggregates. The predominant aggregate sedimented at 11S and had a mol.wt greater than or equal to 200 000. Two non-cross-reacting antigens were present in the aggregate mixture. The presence of these two antigens does not reflect the presence of two different matrix proteins; rather, the expression of the antigens correlates with the degree of aggregation of the matrix protein.", "contents": "Characterization and serology of the matrix protein from a nuclear-polyhedrosis virus of Trichoplusia ni before and after degradation by an endogenous proteinase. The intact matrix protein from a nuclear-polyhedrosis virus of the cabbage looper (Trichoplusia ni), isolated after inhibition of an endogenous serine-type proteinase, was further purified by molecular-sieve chromatography. The matrix protein was associated with carbohydrate moieties, and the carbohydrate content was determined for the two major peptides isolated after proteolysis by the endogenous proteinase. The association-dissociation interactions of the intact and proteinase-hydrolysed monomer units were characterized at high and low pH. At pH1.9, proteinase-degraded matrix protein dissociated into two different peptide fractions, FI and FII. Fraction FII, a single peptide of 9400 daltons, comprised one-third of the monomer unit of 28 000 daltons. At pH9.5, the degraded peptides were tightly associated in units equivalent to the intact monomer. These monomer equivalents associated to form a series of interconverting aggregates. The predominant aggregate sedimented at 11S and had a mol.wt greater than or equal to 200 000. Two non-cross-reacting antigens were present in the aggregate mixture. The presence of these two antigens does not reflect the presence of two different matrix proteins; rather, the expression of the antigens correlates with the degree of aggregation of the matrix protein."}
{"id": "PMID:23108", "title": "Affinity chromatography of aminoacyl-transfer ribonucleic acid synthetases. Cognate transfer ribonucleic acid as a ligand.", "content": "The use of tRNA affinity columns for the purification of aminoacyl-tRNA synthetases was investigated. A purification method for valyl-tRNA synthetase from Bacillus stearothermophilus is described that uses two affinity columns, one containing the pure cognate tRNA, and the other containing all tRNA species except the cognate tRNA. A method for the rapid preparation of the two columns was developed, which does not require prior isolation of cognate tRNA but makes use of the ability of the target synthetase to select its cognate tRNA. The usefulness of tRNA columns is compared with that of affinity columns derived from the aminoalkyladenylate reported in the preceding paper [Clarke & Knowles (1977) Biochem J. 167, 405-417].", "contents": "Affinity chromatography of aminoacyl-transfer ribonucleic acid synthetases. Cognate transfer ribonucleic acid as a ligand. The use of tRNA affinity columns for the purification of aminoacyl-tRNA synthetases was investigated. A purification method for valyl-tRNA synthetase from Bacillus stearothermophilus is described that uses two affinity columns, one containing the pure cognate tRNA, and the other containing all tRNA species except the cognate tRNA. A method for the rapid preparation of the two columns was developed, which does not require prior isolation of cognate tRNA but makes use of the ability of the target synthetase to select its cognate tRNA. The usefulness of tRNA columns is compared with that of affinity columns derived from the aminoalkyladenylate reported in the preceding paper [Clarke & Knowles (1977) Biochem J. 167, 405-417]."}
{"id": "PMID:23109", "title": "Activation studies of the multiple forms of prochymosin (prorennin).", "content": "Activation of the four separate components of prochymosin (prorennin) at pH 5.0 demonstrated that each zymogen was the precursor to an electrophoretically distinct chymosin (rennin). When the increase in milk-clotting activity with time was analysed, the mechanism of activation of unfractionated prochymosin, individual prochymosin components, and a mixture of the prochymosin fractions at pH 5.0 was shown to follow essentially autocatalytic kinetics. The activation of prochymosin C was completed in 70 h, whereas the other three fractions each required more than 110 h for complete activation under the same conditions. Intact prochymosin, the mixture of four components and prochymosin C were activated at similar rates. Interaction of the individual fractions during activation is suggested to explain the increased rate of the activation for the mixture. Comparison of autocatalytic activation of unfractionated prochymosin purified chromatographically at pH 6.7 and 5.7 demonstrated an increased rate of reaction of the zymogen prepared at the lower pH value. The possibility that prochymosin became susceptible to activation during preparation at pH values slightly below 6.0, as a result of changes in the proportion of the components or a conformational change and exposure of the active site, is discussed.", "contents": "Activation studies of the multiple forms of prochymosin (prorennin). Activation of the four separate components of prochymosin (prorennin) at pH 5.0 demonstrated that each zymogen was the precursor to an electrophoretically distinct chymosin (rennin). When the increase in milk-clotting activity with time was analysed, the mechanism of activation of unfractionated prochymosin, individual prochymosin components, and a mixture of the prochymosin fractions at pH 5.0 was shown to follow essentially autocatalytic kinetics. The activation of prochymosin C was completed in 70 h, whereas the other three fractions each required more than 110 h for complete activation under the same conditions. Intact prochymosin, the mixture of four components and prochymosin C were activated at similar rates. Interaction of the individual fractions during activation is suggested to explain the increased rate of the activation for the mixture. Comparison of autocatalytic activation of unfractionated prochymosin purified chromatographically at pH 6.7 and 5.7 demonstrated an increased rate of reaction of the zymogen prepared at the lower pH value. The possibility that prochymosin became susceptible to activation during preparation at pH values slightly below 6.0, as a result of changes in the proportion of the components or a conformational change and exposure of the active site, is discussed."}
{"id": "PMID:23110", "title": "Electron-paramagnetic-resonance studies of leghaemoglobins from soya-bean and cowpea root nodules. Identification of nitrosyl-leghaemoglobin in crude leghaemoglobin preparations.", "content": "1. Leghaemoglobins from soya-bean (Glycine max) and cowpea (Vigna unguiculata) root nodules were purified by chromatography on DEAE-cellulose phosphate columns at pH8.0 and pH5.8, to avoid the relatively low pH (5.2) commonly used to purify these proteins. 2. E.p.r. (electron-paramagnetic-resonance) spectra of the fluoride, azide, hydroxide and cyanide complexes of these ferric leghaemoglobins were very similar to the spectra of the corresponding myoglobin derivatives, indicating that the immediate environment of the iron in leghaemoglobin and myoglobin is similar, an imidazole moiety of histidine being the proximal ligand to the haem iron [cf. Appleby, Blumberg, Peisach, Wittenberg & Wittenberg (1976) J. Biol. Chem.251, 6090-6096]. 3. E.p.r. spectra of the acid-metleghaemoglobins showed prominent high-spin features very near g=6 and g=2 and, unlike myoglobin, small low-spin absorptions near g=2.26, 2.72 and 3.14. The width of the g=6 absorption derivative at 10-20K was about 4-4.5mT, similar to the value for acid-methaemoglobin. In contrast, a recently published (Appleby et al., 1976) spectrum of acid-metleghaemoglobin a had less high-spin character and a much broader absorption derivative around g=6. 4. E.p.r. spectra of ferric leghaemoglobin nicotinate and imidazole complexes suggest that the low-spin absorption near g=3.14 can be attributed to a trace of ferric leghaemoglobin nicotinate, and those near g=2.26 and 2.72 are from an endogenous dihistidyl haemichrome. 5. A large e.p.r. signal at g=2 in all samples of crude leghaemoglobin was shown to be from nitrosyl-leghaemoglobin. A soya-bean sample contained 27+/-3% of the latter. A previously unidentified form of soya-bean ferrous leghaemoglobin a was shown to be its nitrosyl derivative. If this is not an artifact, and occurs in the root nodule, the nitrosyl radical may interfere with the function of leghaemoglobin.", "contents": "Electron-paramagnetic-resonance studies of leghaemoglobins from soya-bean and cowpea root nodules. Identification of nitrosyl-leghaemoglobin in crude leghaemoglobin preparations. 1. Leghaemoglobins from soya-bean (Glycine max) and cowpea (Vigna unguiculata) root nodules were purified by chromatography on DEAE-cellulose phosphate columns at pH8.0 and pH5.8, to avoid the relatively low pH (5.2) commonly used to purify these proteins. 2. E.p.r. (electron-paramagnetic-resonance) spectra of the fluoride, azide, hydroxide and cyanide complexes of these ferric leghaemoglobins were very similar to the spectra of the corresponding myoglobin derivatives, indicating that the immediate environment of the iron in leghaemoglobin and myoglobin is similar, an imidazole moiety of histidine being the proximal ligand to the haem iron [cf. Appleby, Blumberg, Peisach, Wittenberg & Wittenberg (1976) J. Biol. Chem.251, 6090-6096]. 3. E.p.r. spectra of the acid-metleghaemoglobins showed prominent high-spin features very near g=6 and g=2 and, unlike myoglobin, small low-spin absorptions near g=2.26, 2.72 and 3.14. The width of the g=6 absorption derivative at 10-20K was about 4-4.5mT, similar to the value for acid-methaemoglobin. In contrast, a recently published (Appleby et al., 1976) spectrum of acid-metleghaemoglobin a had less high-spin character and a much broader absorption derivative around g=6. 4. E.p.r. spectra of ferric leghaemoglobin nicotinate and imidazole complexes suggest that the low-spin absorption near g=3.14 can be attributed to a trace of ferric leghaemoglobin nicotinate, and those near g=2.26 and 2.72 are from an endogenous dihistidyl haemichrome. 5. A large e.p.r. signal at g=2 in all samples of crude leghaemoglobin was shown to be from nitrosyl-leghaemoglobin. A soya-bean sample contained 27+/-3% of the latter. A previously unidentified form of soya-bean ferrous leghaemoglobin a was shown to be its nitrosyl derivative. If this is not an artifact, and occurs in the root nodule, the nitrosyl radical may interfere with the function of leghaemoglobin."}
{"id": "PMID:23111", "title": "Evidence for the role of vitamin C-6 as a cofactor of lysyl oxidase.", "content": "At 24 h after injection of 16-day chick embryos with [C-3H]pyridoxine hydrochloride, some of this label appears in the epiphysial cartilage. Over 35% of this radioactivity appears in the form of [G-3H]pyridoxal and a further 30% as other vitamin B-6 compounds. Partial purification of lysyl oxidase from the labelled epiphysial cartilage reveals a single peak of radioactivity coinciding with a single peak of enzyme activity. On dialysis against phosphate-buffered saline, 75% of this radioactivity is found to be non-diffusible. After incubation with isonicotinic acid hydrazide, a carbonyl reagent that appears to inhibit lysyl oxidase both in vivo and in vitro, a further 70% of the radioactivity is lost, with a roughly corresponding loss of enzyme activity. It is suggested that a form of vitamin B-6 is required as a cofactor of lysyl oxidase, and that this may have important implications in terms of connective-tissue metabolism.", "contents": "Evidence for the role of vitamin C-6 as a cofactor of lysyl oxidase. At 24 h after injection of 16-day chick embryos with [C-3H]pyridoxine hydrochloride, some of this label appears in the epiphysial cartilage. Over 35% of this radioactivity appears in the form of [G-3H]pyridoxal and a further 30% as other vitamin B-6 compounds. Partial purification of lysyl oxidase from the labelled epiphysial cartilage reveals a single peak of radioactivity coinciding with a single peak of enzyme activity. On dialysis against phosphate-buffered saline, 75% of this radioactivity is found to be non-diffusible. After incubation with isonicotinic acid hydrazide, a carbonyl reagent that appears to inhibit lysyl oxidase both in vivo and in vitro, a further 70% of the radioactivity is lost, with a roughly corresponding loss of enzyme activity. It is suggested that a form of vitamin B-6 is required as a cofactor of lysyl oxidase, and that this may have important implications in terms of connective-tissue metabolism."}
{"id": "PMID:23112", "title": "Pre-steady-state kinetic studies on cytoplasmic sheep liver aldehyde dehydrogenase.", "content": "Stopped-flow experiments in which sheep liver cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) was rapidly mixed with NAD(+) and aldehyde showed a burst of NADH formation, followed by a slower steady-state turnover. The kinetic data obtained when the relative concentrations and orders of mixing of NAD(+) and propionaldehyde with the enzyme were varied were fitted to the following mechanism: [Formula: see text] where the release of NADH is slow. By monitoring the quenching of protein fluorescence on the binding of NAD(+), estimates of 2x10(5) litre.mol(-1).s(-1) and 2s(-1) were obtained for k(+1) and k(-1) respectively. Although k(+3) could be determined from the dependence of the burst rate constant on the concentration of propionaldehyde to be 11s(-1), k(+2) and k(-2) could not be determined uniquely, but could be related by the equation: (k(-2)+k(+3))/k(+2) =50x10(-6)mol.litre(-1). No significant isotope effect was observed when [1-(2)H]propionaldehyde was used as substrate. The burst rate constant was pH-dependent, with the greatest rate constants occurring at high pH. Similar data were obtained by using acetaldehyde, where for this substrate (k(-2)+k(+3))/k(+2)=2.3x10 (-3)mol.litre(-1) and k(+3) is 23s(-1). When [1,2,2,2-(2)H]acetaldehyde was used, no isotope effect was observed on k(+3), but there was a significant effect on k(+2) and k(-2). A burst of NADH production has also been observed with furfuraldehyde, trans-4-(NN-dimethylamino)cinnamaldehyde, formaldehyde, benzaldehyde, 4-(imidazol-2-ylazo)benzaldehyde, p-methoxybenzaldehyde and p-methylbenzaldehyde as substrates, but not with p-nitrobenzaldehyde.", "contents": "Pre-steady-state kinetic studies on cytoplasmic sheep liver aldehyde dehydrogenase. Stopped-flow experiments in which sheep liver cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) was rapidly mixed with NAD(+) and aldehyde showed a burst of NADH formation, followed by a slower steady-state turnover. The kinetic data obtained when the relative concentrations and orders of mixing of NAD(+) and propionaldehyde with the enzyme were varied were fitted to the following mechanism: [Formula: see text] where the release of NADH is slow. By monitoring the quenching of protein fluorescence on the binding of NAD(+), estimates of 2x10(5) litre.mol(-1).s(-1) and 2s(-1) were obtained for k(+1) and k(-1) respectively. Although k(+3) could be determined from the dependence of the burst rate constant on the concentration of propionaldehyde to be 11s(-1), k(+2) and k(-2) could not be determined uniquely, but could be related by the equation: (k(-2)+k(+3))/k(+2) =50x10(-6)mol.litre(-1). No significant isotope effect was observed when [1-(2)H]propionaldehyde was used as substrate. The burst rate constant was pH-dependent, with the greatest rate constants occurring at high pH. Similar data were obtained by using acetaldehyde, where for this substrate (k(-2)+k(+3))/k(+2)=2.3x10 (-3)mol.litre(-1) and k(+3) is 23s(-1). When [1,2,2,2-(2)H]acetaldehyde was used, no isotope effect was observed on k(+3), but there was a significant effect on k(+2) and k(-2). A burst of NADH production has also been observed with furfuraldehyde, trans-4-(NN-dimethylamino)cinnamaldehyde, formaldehyde, benzaldehyde, 4-(imidazol-2-ylazo)benzaldehyde, p-methoxybenzaldehyde and p-methylbenzaldehyde as substrates, but not with p-nitrobenzaldehyde."}
{"id": "PMID:23113", "title": "A model for the allosteric regulation of pH-sensitive enzymes.", "content": "1. In an enzyme that has two independent binding sites for a ligand, any inhibitor that binds solely to the free enzyme will give rise to positive co-operativity. 2. A model is considered for the allosteric control of enzymes by effectors in which their effects are mediated by ligand-induced perturbations of the ionization constants of a group or groups involved in the binding of substrate to the active site. 3. The model described offers a plausible explanation for the observation that the sigmoidal initial-rate curves reported for some regulatory enzymes are not expressed at all pH values where the enzyme is catalytically active.", "contents": "A model for the allosteric regulation of pH-sensitive enzymes. 1. In an enzyme that has two independent binding sites for a ligand, any inhibitor that binds solely to the free enzyme will give rise to positive co-operativity. 2. A model is considered for the allosteric control of enzymes by effectors in which their effects are mediated by ligand-induced perturbations of the ionization constants of a group or groups involved in the binding of substrate to the active site. 3. The model described offers a plausible explanation for the observation that the sigmoidal initial-rate curves reported for some regulatory enzymes are not expressed at all pH values where the enzyme is catalytically active."}
{"id": "PMID:23114", "title": "The reaction of Fe(III) myoglobin fluoride with reducing agents.", "content": "The reaction of reducing agents with Fe(III) myoglobin fluoride from sperm whale was studied at alkaline pH values. The rate of reduction by dithionite was indistinguishable from the rate of ligand dissociation even when the values of the rate constants for both were only 1.0 X 10(-3)S-1 (at pH 10.6). Reduction by the reduced Methyl Viologen radical ion and reduced Safranine was faster than the rate of dissociation, providing evidence that these reductants can donate electrons to the iron centre via a pathway involving an (undetectable) liganded Fe(II) intermediate.", "contents": "The reaction of Fe(III) myoglobin fluoride with reducing agents. The reaction of reducing agents with Fe(III) myoglobin fluoride from sperm whale was studied at alkaline pH values. The rate of reduction by dithionite was indistinguishable from the rate of ligand dissociation even when the values of the rate constants for both were only 1.0 X 10(-3)S-1 (at pH 10.6). Reduction by the reduced Methyl Viologen radical ion and reduced Safranine was faster than the rate of dissociation, providing evidence that these reductants can donate electrons to the iron centre via a pathway involving an (undetectable) liganded Fe(II) intermediate."}
{"id": "PMID:23115", "title": "2-Deoxy-D-galactose, a substrate for the galactose-transport system of Escherichia coli.", "content": "The following observations showed that 2-deoxy-D-galactose is a useful tool for the isolation and elucidation of the activity of one system for galactose uptake into Escherichia coli. 1. 2-Deoxygalactose, which is not a substrate for growth of E. coli, was transported into strains of the organism induced for galactose transport. 2. By using appropriate mutants it was shown that 2-deoxygalactose is a much better substrate for the galactose-transport system than for the methyl galactoside-transport system. This was confirmed by the results of mutual inhibition studies with substrates of each transport system. 3. The glucose-, arabinose- or lactose-transport systems did not effect significant transport of 2-deoxygalactose. 4. Like other substrates of the galactose-transport system, 2-deoxygalactose promoted effective proton uptake into de-energized suspensions of appropriate E. coli strains. 5. The S183 series of E. coli mutants were found to contain a constitutive galactose-transport system, if 2-deoxygalactose transport is used as one criterion for such activity.", "contents": "2-Deoxy-D-galactose, a substrate for the galactose-transport system of Escherichia coli. The following observations showed that 2-deoxy-D-galactose is a useful tool for the isolation and elucidation of the activity of one system for galactose uptake into Escherichia coli. 1. 2-Deoxygalactose, which is not a substrate for growth of E. coli, was transported into strains of the organism induced for galactose transport. 2. By using appropriate mutants it was shown that 2-deoxygalactose is a much better substrate for the galactose-transport system than for the methyl galactoside-transport system. This was confirmed by the results of mutual inhibition studies with substrates of each transport system. 3. The glucose-, arabinose- or lactose-transport systems did not effect significant transport of 2-deoxygalactose. 4. Like other substrates of the galactose-transport system, 2-deoxygalactose promoted effective proton uptake into de-energized suspensions of appropriate E. coli strains. 5. The S183 series of E. coli mutants were found to contain a constitutive galactose-transport system, if 2-deoxygalactose transport is used as one criterion for such activity."}
{"id": "PMID:23116", "title": "Evidence for an electrogenic 3-deoxy-2-oxo-D-gluconate--proton co-transport driven by the protonmotive force in Escherichia coli K12.", "content": "Evidence is presented indicating that the carrier-mediated uptake of 3-deoxy-2-oxo-D-gluconate and D-glucuronate in Escherichia coli K12 is driven by the deltapH and deltapsi components of the protonmotive force. 1. Approximately two protons enter the cells with each sugar molecule, independent of the sugar and the strain used. 2. In respiring cells, the magnitude of the pH gradient alone, as measured by distribution of [3H]acetate, appears to be insufficient to account for the chemical gradient of 3-deoxy-2-oxo-D-gluconate that is developed between pH 6.0 and 8.0. 3. If the external pH is varied between 5.5 and 8.0, 3-deoxy-2-oxo-D-gluconate uptake is gradually inhibited by valinomycin plus K+ ions, whereas the inhibition caused by nigericin is concomitantly relieved, thus reflecting the relative contribution of deltapH and deltapsi to the total protonmotive force at each external pH. 4. 3-Deoxy-2-oxo-D-gluconate can be transiently accumulated into isolated membrane vesicles in response to an artificially induced pH gradient. The process is stimulated when the membrane potential is collapsed by valinomycin in the presence of K+ ions.", "contents": "Evidence for an electrogenic 3-deoxy-2-oxo-D-gluconate--proton co-transport driven by the protonmotive force in Escherichia coli K12. Evidence is presented indicating that the carrier-mediated uptake of 3-deoxy-2-oxo-D-gluconate and D-glucuronate in Escherichia coli K12 is driven by the deltapH and deltapsi components of the protonmotive force. 1. Approximately two protons enter the cells with each sugar molecule, independent of the sugar and the strain used. 2. In respiring cells, the magnitude of the pH gradient alone, as measured by distribution of [3H]acetate, appears to be insufficient to account for the chemical gradient of 3-deoxy-2-oxo-D-gluconate that is developed between pH 6.0 and 8.0. 3. If the external pH is varied between 5.5 and 8.0, 3-deoxy-2-oxo-D-gluconate uptake is gradually inhibited by valinomycin plus K+ ions, whereas the inhibition caused by nigericin is concomitantly relieved, thus reflecting the relative contribution of deltapH and deltapsi to the total protonmotive force at each external pH. 4. 3-Deoxy-2-oxo-D-gluconate can be transiently accumulated into isolated membrane vesicles in response to an artificially induced pH gradient. The process is stimulated when the membrane potential is collapsed by valinomycin in the presence of K+ ions."}
{"id": "PMID:23117", "title": "Passive ion permeability of the chromaffin-granule membrane.", "content": "'Ghosts' of bovine chromaffin granules, in which the complex mixture of proteins and solutes normally found in the granule matrix is replaced by buffered sucrose are osmotically sensitive. They shrink when the osmotic pressure of the suspension medium is increased, and swell if solute entry is facilitated by the addition of ionophores. Swelling in the presence of ionophores has been used to investigate the passive ion permeability of these membranes. They have a very low permeability to K+ ions (of the order of 10(-10) cm/s); their permeability to protons, Na+ and choline ions is too low to be detected by these methods. Their passive permeability to anions decreases in the order: CNS- greater than I- greater than CCl3CO2- greater than Br- greater than Cl- greater than SO4(2)- greater than CH3CO2-, HCO3-, F-, PO4(3)- the permeability to hiocyanate being of the order of 10(-7) cm/s. Coupled proton and anion entry is extremely slow, except for weak acids. Fluoride, unexpectedly, also appears to enter rapidly when proton/K+ exchange is facilitated by nigericin. In the presence of K+ salts, nigericin, like valinomycin, induces lysis of intact granules, an effect that is not dependent on the presence of a permeant anion, but is dependent on the pH gradient across the membrane.", "contents": "Passive ion permeability of the chromaffin-granule membrane. 'Ghosts' of bovine chromaffin granules, in which the complex mixture of proteins and solutes normally found in the granule matrix is replaced by buffered sucrose are osmotically sensitive. They shrink when the osmotic pressure of the suspension medium is increased, and swell if solute entry is facilitated by the addition of ionophores. Swelling in the presence of ionophores has been used to investigate the passive ion permeability of these membranes. They have a very low permeability to K+ ions (of the order of 10(-10) cm/s); their permeability to protons, Na+ and choline ions is too low to be detected by these methods. Their passive permeability to anions decreases in the order: CNS- greater than I- greater than CCl3CO2- greater than Br- greater than Cl- greater than SO4(2)- greater than CH3CO2-, HCO3-, F-, PO4(3)- the permeability to hiocyanate being of the order of 10(-7) cm/s. Coupled proton and anion entry is extremely slow, except for weak acids. Fluoride, unexpectedly, also appears to enter rapidly when proton/K+ exchange is facilitated by nigericin. In the presence of K+ salts, nigericin, like valinomycin, induces lysis of intact granules, an effect that is not dependent on the presence of a permeant anion, but is dependent on the pH gradient across the membrane."}
{"id": "PMID:23130", "title": "Lipid metabolism in spontaneously hypertensive rats (SHR).", "content": "Plasma cholesterol was lower in spontaneously hypertensive rats (SHR), while plasma triglyceride and free fatty acid were increased in comparison with control normotensive Wistar-Kyoto (WK) rats. Correspondingly, [1-14C]-acetate incorporation into liver cholesterol was clearly decreased in SHR as compared with WK. As for lipogenic enzyme activities, glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase in SHR were respectively decreased, increased and not significantly different, in comparison with WK rats. Liver cholesterol was rather low and cardiac triglyceride was slightly increased in SHR. Aortic cholesterol and triglyceride levels were not significantly different between SHR AND WK rats. Thus, SHR have an abnormality in lipid metabolism, especially in cholesterol synthesis, but the pathological implication of this in hypertension and related vascular lesions is not yet clear.", "contents": "Lipid metabolism in spontaneously hypertensive rats (SHR). Plasma cholesterol was lower in spontaneously hypertensive rats (SHR), while plasma triglyceride and free fatty acid were increased in comparison with control normotensive Wistar-Kyoto (WK) rats. Correspondingly, [1-14C]-acetate incorporation into liver cholesterol was clearly decreased in SHR as compared with WK. As for lipogenic enzyme activities, glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase in SHR were respectively decreased, increased and not significantly different, in comparison with WK rats. Liver cholesterol was rather low and cardiac triglyceride was slightly increased in SHR. Aortic cholesterol and triglyceride levels were not significantly different between SHR AND WK rats. Thus, SHR have an abnormality in lipid metabolism, especially in cholesterol synthesis, but the pathological implication of this in hypertension and related vascular lesions is not yet clear."}
{"id": "PMID:23134", "title": "Assessment of combined oral theophylline and inhaled beta-adrenoceptor agonist bronchodilator therapy.", "content": "1. The bronchodilator effects of 500 microgram rimiterol by pressurized aerosol, 375 mg oral theophylline and both drugs in combination were compared in a randomized, placebo-controlled, double-blind trial in eight patients with chronic, partially reversible airways obstruction. 2. The four treatments were (i) oral theophylline, placebo aerosol (TP); (ii) oral placebo, rimiterol aerosol (PR); (iii) oral theophylline, rimiterol aerosol (TR) and; (iv) oral placebo, placebo aerosol (PP). The aerosol was administered 2 h after the oral treatment. 3. Significant bronchodilatation (% FEV1 change from control) compared to PP occurred with TP from 60 to 480 min and with TR from 60 to 300 min, whereas with PR only for 45 min (P less than 0.05). 4. The mean, peak % FEV1 increases from control were 51.8% at 125 min, 31.7% at 125 min, 26.1% at 210 min and 0.9% at 30 min for TR, PR, TP and PP respectively. 5. At 125 min (5 min after aerosol inhalation) the mean % FEV1 change from control with TR (51.8%) Was significantly greater than with PR (31.7%), TP (22.2%) (P less than 0.05) and PP (-2.4%) (P less than 0.01). 6. The mean, peak plasma theophylline levels were 10.19 microgram/ml at 120 min and 9.98 microgram/ml at 180 min with TR and TP respectively. Theophylline half-life ranged between 4.3 and 12.5 h (mean +/- s.e. mean, 8.0 +/- 0.8 h). 7. Additive bronchodilatation was produced when rimiterol was administered with theophylline at a time when therapeutic plasma theophylline levels were achieved.", "contents": "Assessment of combined oral theophylline and inhaled beta-adrenoceptor agonist bronchodilator therapy. 1. The bronchodilator effects of 500 microgram rimiterol by pressurized aerosol, 375 mg oral theophylline and both drugs in combination were compared in a randomized, placebo-controlled, double-blind trial in eight patients with chronic, partially reversible airways obstruction. 2. The four treatments were (i) oral theophylline, placebo aerosol (TP); (ii) oral placebo, rimiterol aerosol (PR); (iii) oral theophylline, rimiterol aerosol (TR) and; (iv) oral placebo, placebo aerosol (PP). The aerosol was administered 2 h after the oral treatment. 3. Significant bronchodilatation (% FEV1 change from control) compared to PP occurred with TP from 60 to 480 min and with TR from 60 to 300 min, whereas with PR only for 45 min (P less than 0.05). 4. The mean, peak % FEV1 increases from control were 51.8% at 125 min, 31.7% at 125 min, 26.1% at 210 min and 0.9% at 30 min for TR, PR, TP and PP respectively. 5. At 125 min (5 min after aerosol inhalation) the mean % FEV1 change from control with TR (51.8%) Was significantly greater than with PR (31.7%), TP (22.2%) (P less than 0.05) and PP (-2.4%) (P less than 0.01). 6. The mean, peak plasma theophylline levels were 10.19 microgram/ml at 120 min and 9.98 microgram/ml at 180 min with TR and TP respectively. Theophylline half-life ranged between 4.3 and 12.5 h (mean +/- s.e. mean, 8.0 +/- 0.8 h). 7. Additive bronchodilatation was produced when rimiterol was administered with theophylline at a time when therapeutic plasma theophylline levels were achieved."}
{"id": "PMID:23135", "title": "Clazepam: pharmacokinetics and effects on performance.", "content": "1. The effects of clazepam, a new benzodiazepine (30 mg orally) on performance tests and the cardiovascular system have been compared to those of chlordiazepoxide (30 mg orally) and a placebo in a double-blind trial involving six healthy volunteers. Simultaneously, the pharmacokinetics of clazepam were investigated. 2. While clazepam itself could be detected neither in plasma nor in urine, it gave rise to two plasma metabolites, the former, an alcoholic derivative with a short half-life, and the second, desmethyldiazepam, with a long half-life. These two metabolites and oxazepam were excreted in urine and, within the 24 h period following drug intake, accounted for 73% of the ingested dose. 3. Seven hours after its administration, clazepam slightly improved performance and reduced anxiety. The kinetics of these effects and the metabolic data suggest that clazepam acts mainly through the formation of desmethyldiazepam. However, owing to the low blood levels of this metabolite, the activity of clazepam was very moderate.", "contents": "Clazepam: pharmacokinetics and effects on performance. 1. The effects of clazepam, a new benzodiazepine (30 mg orally) on performance tests and the cardiovascular system have been compared to those of chlordiazepoxide (30 mg orally) and a placebo in a double-blind trial involving six healthy volunteers. Simultaneously, the pharmacokinetics of clazepam were investigated. 2. While clazepam itself could be detected neither in plasma nor in urine, it gave rise to two plasma metabolites, the former, an alcoholic derivative with a short half-life, and the second, desmethyldiazepam, with a long half-life. These two metabolites and oxazepam were excreted in urine and, within the 24 h period following drug intake, accounted for 73% of the ingested dose. 3. Seven hours after its administration, clazepam slightly improved performance and reduced anxiety. The kinetics of these effects and the metabolic data suggest that clazepam acts mainly through the formation of desmethyldiazepam. However, owing to the low blood levels of this metabolite, the activity of clazepam was very moderate."}
{"id": "PMID:23136", "title": "Studies of cardioselectivity and partial agonist activity in beta-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise.", "content": "1 The effects of beta-adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double-blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise-induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha-adrenoceptor blockade helps to maintain exercise-induced increase in PEFR.", "contents": "Studies of cardioselectivity and partial agonist activity in beta-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise. 1 The effects of beta-adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double-blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise-induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha-adrenoceptor blockade helps to maintain exercise-induced increase in PEFR."}
{"id": "PMID:23132", "title": "[Salicylate poisoning. Determination of the free fraction using the ultrafiltration method].", "content": "Seventeen infants under one year of age admitted to the Emergency Service of the General Hospital of the Medical Center La Raza during the year 1976 were included in this study with the diagnosis of salicylate poisoning. Determination of plasma salicylate by the ultrafiltrate method was practiced to all patients. A direct relationship between total plasmatic salicylate and its free fraction was found together with an inverse proportion between percentage of total free--salicylate and plasma pH and a lineal correlation between plasma free--salicylate and salicylate obtained in spinal fluid. It is concluded that determination of the free fraction of plasma salicylate is an easy diagnostic method for the better evaluation of salicylate acid poisoning in the infant.", "contents": "[Salicylate poisoning. Determination of the free fraction using the ultrafiltration method]. Seventeen infants under one year of age admitted to the Emergency Service of the General Hospital of the Medical Center La Raza during the year 1976 were included in this study with the diagnosis of salicylate poisoning. Determination of plasma salicylate by the ultrafiltrate method was practiced to all patients. A direct relationship between total plasmatic salicylate and its free fraction was found together with an inverse proportion between percentage of total free--salicylate and plasma pH and a lineal correlation between plasma free--salicylate and salicylate obtained in spinal fluid. It is concluded that determination of the free fraction of plasma salicylate is an easy diagnostic method for the better evaluation of salicylate acid poisoning in the infant."}
{"id": "PMID:23138", "title": "The effects of chronic drug administration on hepatic enzyme induction and folate metabolism.", "content": "1 Patients on prolonged treatment with anticonvulsant and phenothiazine drugs exhibited lower than normal concentrations of folate in serum and erythrocytes, and showed increased urinary FIGLU excretion after histidine loading; urinary excretion of D-glucaric acid was also increased suggesting induction of the hepatic microsomal enzymes. 2 Folate deficiency by enzyme-inducing drugs was seen to be determined more by the duration of therapy than by the nature of the drugs. Excretion of FIGLU was increased by 70% by 2-5 years of treatment with anticonvulsant, phenothiazine or tricyclic drugs, and by 200% after 6 or more years. 3 Hepatic microsomal enzyme induction, as measured by D-glucaric acid excretion, was greatest after 2-5 years treatment. 4 It is suggested that the increased requirements for folate, resulting from microsomal enzyme induction, lead to folate deficiency and this subsequently limits enzyme induction, leading to adverse drug side-affects. 5 The dietary folate of hospitalized patients would seem to be generally inadequate for patients on long term treatment with enzyme-inducing drugs.", "contents": "The effects of chronic drug administration on hepatic enzyme induction and folate metabolism. 1 Patients on prolonged treatment with anticonvulsant and phenothiazine drugs exhibited lower than normal concentrations of folate in serum and erythrocytes, and showed increased urinary FIGLU excretion after histidine loading; urinary excretion of D-glucaric acid was also increased suggesting induction of the hepatic microsomal enzymes. 2 Folate deficiency by enzyme-inducing drugs was seen to be determined more by the duration of therapy than by the nature of the drugs. Excretion of FIGLU was increased by 70% by 2-5 years of treatment with anticonvulsant, phenothiazine or tricyclic drugs, and by 200% after 6 or more years. 3 Hepatic microsomal enzyme induction, as measured by D-glucaric acid excretion, was greatest after 2-5 years treatment. 4 It is suggested that the increased requirements for folate, resulting from microsomal enzyme induction, lead to folate deficiency and this subsequently limits enzyme induction, leading to adverse drug side-affects. 5 The dietary folate of hospitalized patients would seem to be generally inadequate for patients on long term treatment with enzyme-inducing drugs."}
{"id": "PMID:23143", "title": "Thermodynamics of the denaturation of pepsinogen by urea.", "content": "The denaturation of swine pepsinogen has been studied as a function of urea concentration, pH, and temperature. The unfolding of the protein by urea has been found to be fully reversible under different conditions of pH, temperature, and denaturant concentration. Kinetic experiments have shown that the transition shows two-state behavior at 25 degrees C in the pH range 6-8 covered in this study. Analysis of the  equilibrium data obtained at 25 degrees C according to Tanford (Tanford, C. (1970), Adv. Protein Chem. 24, 1) and Pace (Pace, N.C. (1975), Crit. Rev. Biochem. 3, 1) leads to the conclusion that the free energy of stabilization of native pepsinogen, relative to the denatured state, under physiological conditions, is only 6-12 kcal mol-1. The temperature dependence of the equilibrium constant for the unfolding of pepsinogen by urea in the range 20-50 degrees C at pH 8.0 can be described by assigning the following values of thermodynamic parameters for the denaturation at 25 degrees C: deltaH=31.5 kcal mol-1; deltaS=105 cal deg-1 mol-1; and deltaCp=5215 cal deg-1 mol-1.", "contents": "Thermodynamics of the denaturation of pepsinogen by urea. The denaturation of swine pepsinogen has been studied as a function of urea concentration, pH, and temperature. The unfolding of the protein by urea has been found to be fully reversible under different conditions of pH, temperature, and denaturant concentration. Kinetic experiments have shown that the transition shows two-state behavior at 25 degrees C in the pH range 6-8 covered in this study. Analysis of the  equilibrium data obtained at 25 degrees C according to Tanford (Tanford, C. (1970), Adv. Protein Chem. 24, 1) and Pace (Pace, N.C. (1975), Crit. Rev. Biochem. 3, 1) leads to the conclusion that the free energy of stabilization of native pepsinogen, relative to the denatured state, under physiological conditions, is only 6-12 kcal mol-1. The temperature dependence of the equilibrium constant for the unfolding of pepsinogen by urea in the range 20-50 degrees C at pH 8.0 can be described by assigning the following values of thermodynamic parameters for the denaturation at 25 degrees C: deltaH=31.5 kcal mol-1; deltaS=105 cal deg-1 mol-1; and deltaCp=5215 cal deg-1 mol-1."}
{"id": "PMID:23144", "title": "Arginine decarboxylase from Escherichia coli B: mechanism of dissociation from the decamer to the dimer.", "content": "The mechanism by which arginine decarboxylase dissociates from a decamer to a dimer has been examined by allowing a sulfhydryl group, available in the dimer but not the decamer, to react with 5,5'-dithiobis(2-nitrobenzoic acid). Initial rates of dissociation were obtained by following the resulting increase in absorbance at 412 nm in a stopped-flow spectrophotometer. The rate of dissociation increases linearly with the protein concentration and reaches a maximum as a function of the concentrations of 5,5'-dithiobis(2-nitrobenzoic acid), Na+, and 1/[H+]. Experiments in which the rate of dissociation was measured while one reagent was varied at fixed levels of a second indicate that dissociation requires three events: binding of one Na+ ion, dissociation of one proton, and the irreversible dissociation of subunits, in that order. The results also show that the decamer dissociates in stages rather than all at once. The activation energy for the overall process is 16 kcal/mol.", "contents": "Arginine decarboxylase from Escherichia coli B: mechanism of dissociation from the decamer to the dimer. The mechanism by which arginine decarboxylase dissociates from a decamer to a dimer has been examined by allowing a sulfhydryl group, available in the dimer but not the decamer, to react with 5,5'-dithiobis(2-nitrobenzoic acid). Initial rates of dissociation were obtained by following the resulting increase in absorbance at 412 nm in a stopped-flow spectrophotometer. The rate of dissociation increases linearly with the protein concentration and reaches a maximum as a function of the concentrations of 5,5'-dithiobis(2-nitrobenzoic acid), Na+, and 1/[H+]. Experiments in which the rate of dissociation was measured while one reagent was varied at fixed levels of a second indicate that dissociation requires three events: binding of one Na+ ion, dissociation of one proton, and the irreversible dissociation of subunits, in that order. The results also show that the decamer dissociates in stages rather than all at once. The activation energy for the overall process is 16 kcal/mol."}
{"id": "PMID:23145", "title": "Mechanisms and rate equations for dissociating systems.", "content": "The results presented in the previous paper (Boeker, E.A. (1978), Biochemistry 17 (preceding paper in this issue) indicate that the dissociation of the decamer of arginine decarboxylase of Escherichia coli B is enhanced by Na+ and retarded by H+. In this system, substances which increase the rate of dissociation can be treated kinetically either as substrates or activators, and substances which retard dissociation can be treated as products or inhibitors. In addition, the events needed for dissociation can occur in an ordered or a random sequence, and the dissociation itself, from a decamer to five dimers, can be a sequential or a concerted process. In order to provide a framework for the experimental results, mechanisms for the dissociation of arginine decarboxylase that take all of these factors into account are described. In addition, it is shown that the usual methods of steady-state kinetics can be applied to these systems when true initial rates are measured; rate equations are presented for each mechanism. The results can be used for any dissociating of three or more subunits and will describe the dissociation of a dimer under certain conditions.", "contents": "Mechanisms and rate equations for dissociating systems. The results presented in the previous paper (Boeker, E.A. (1978), Biochemistry 17 (preceding paper in this issue) indicate that the dissociation of the decamer of arginine decarboxylase of Escherichia coli B is enhanced by Na+ and retarded by H+. In this system, substances which increase the rate of dissociation can be treated kinetically either as substrates or activators, and substances which retard dissociation can be treated as products or inhibitors. In addition, the events needed for dissociation can occur in an ordered or a random sequence, and the dissociation itself, from a decamer to five dimers, can be a sequential or a concerted process. In order to provide a framework for the experimental results, mechanisms for the dissociation of arginine decarboxylase that take all of these factors into account are described. In addition, it is shown that the usual methods of steady-state kinetics can be applied to these systems when true initial rates are measured; rate equations are presented for each mechanism. The results can be used for any dissociating of three or more subunits and will describe the dissociation of a dimer under certain conditions."}
{"id": "PMID:23151", "title": "Transport in C4 mesophyll chloroplasts: evidence for an exchange of inorganic phosphate and phosphoenolpyruvate.", "content": "1. Mesophyll chloroplasts of the C4 plant Digitaria sanguinalis contain endogenous phosphoenolpyruvate which appears to distribute across the envelope according to the existing pH gradient. The phosphoenolpyruvate remaining in the stroma can be rapidly released by external inorganic phosphate or 3-phosphoglycerate while external pyruvate did not affect the distribution. 2. Phosphoenolpyruvate (PEP) was a competitive inhibitor (Ki (PEP) = 450 micrometer) of 32Pi uptake (Km(Pi)=200 micrometer) by chloroplasts in the dark and also reduced the steady-state internal concentration of 32Pi, which is consistent with phosphate and phosphoenolpyruvate sharing a common carrier. 3. Phosphoenolpyruvate formation by chloroplasts in the light in the presence of pyruvate but in the absence of inorganic phosphate was slow and the concentration ratio of phosphoenolpyruvate (internal/external) was high. Addition of 0.1 mM phosphate induced a high rate of phosphoenolpyruvate formation and the concentration ratio (internal/external) decreased 15-fold. It is proposed that external phosphate is required both for phosphoenolpyruvate formation and efflux from the chloroplast.", "contents": "Transport in C4 mesophyll chloroplasts: evidence for an exchange of inorganic phosphate and phosphoenolpyruvate. 1. Mesophyll chloroplasts of the C4 plant Digitaria sanguinalis contain endogenous phosphoenolpyruvate which appears to distribute across the envelope according to the existing pH gradient. The phosphoenolpyruvate remaining in the stroma can be rapidly released by external inorganic phosphate or 3-phosphoglycerate while external pyruvate did not affect the distribution. 2. Phosphoenolpyruvate (PEP) was a competitive inhibitor (Ki (PEP) = 450 micrometer) of 32Pi uptake (Km(Pi)=200 micrometer) by chloroplasts in the dark and also reduced the steady-state internal concentration of 32Pi, which is consistent with phosphate and phosphoenolpyruvate sharing a common carrier. 3. Phosphoenolpyruvate formation by chloroplasts in the light in the presence of pyruvate but in the absence of inorganic phosphate was slow and the concentration ratio of phosphoenolpyruvate (internal/external) was high. Addition of 0.1 mM phosphate induced a high rate of phosphoenolpyruvate formation and the concentration ratio (internal/external) decreased 15-fold. It is proposed that external phosphate is required both for phosphoenolpyruvate formation and efflux from the chloroplast."}
{"id": "PMID:23152", "title": "Pulse fluorimetry study of energy transfers between tryptophan residues and NADPH in beef liver glutamate dehydrogenase complexes.", "content": "A method is proposed to determine the rates of singlet energy transfers in an array of chromophores containing a finite number of donors and fluorescent acceptors. This method is based on measurements of transfer efficiency coupled with pulse fluorimetry. Three classes of donors can be distinguished which differ in their energy transfer rate. The rates of the first, the second and the third class are respectively greater than, of the order of, and smaller than the emission rate. The method is applied to the study of the energy transfers from tryptophan residues to NADPH, in ternary and quaternary glutamate dehydrogenase complexes. Practically, all these tryptophan residues belong to the first class. They can be divided into two subclasses having different transfer rate values. The distance between these residues and the NADPH site are of the order of 2.5 nm. In addition, the ligand binding induces a protein conformation change, leading to a fluorescence quenching of the tryptophanyl emission.", "contents": "Pulse fluorimetry study of energy transfers between tryptophan residues and NADPH in beef liver glutamate dehydrogenase complexes. A method is proposed to determine the rates of singlet energy transfers in an array of chromophores containing a finite number of donors and fluorescent acceptors. This method is based on measurements of transfer efficiency coupled with pulse fluorimetry. Three classes of donors can be distinguished which differ in their energy transfer rate. The rates of the first, the second and the third class are respectively greater than, of the order of, and smaller than the emission rate. The method is applied to the study of the energy transfers from tryptophan residues to NADPH, in ternary and quaternary glutamate dehydrogenase complexes. Practically, all these tryptophan residues belong to the first class. They can be divided into two subclasses having different transfer rate values. The distance between these residues and the NADPH site are of the order of 2.5 nm. In addition, the ligand binding induces a protein conformation change, leading to a fluorescence quenching of the tryptophanyl emission."}
{"id": "PMID:23153", "title": "Effect of haemolysis on the hexose monophosphate pathway in normal and in glucose-6-phosphate dehydrogenase-deficient erythrocytes.", "content": "The hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49) - deficient erythrocytes is under a severe and unexplained restraint (Gaetani, G.D., Parker, J.C. and Kirkman, H.N. (1974) Proc. Natl. Acad. Sci. U.S. 71, 3584-3587). In this study the hexose monophosphate pathway activity and the NADPH level of normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes were measured soon after haemolysis. The results indicate a prompt increase in 14CO2 evolution and a rise in MADPH levels. Since, in this study, the concentration of the haemolysate is comparable to that of intact erythrocytes, the relief of the restraint on glucose-6-phosphate dehydrogenase through dilution-dependent dissociation from inactivator or inhibitor is excluded. The possibility that the intracellular restraint may result from compartmentalization of glucose-6-phosphate dehydrogenase and substrates or from properties of the intact membrane of the erythrocytes is suggested.", "contents": "Effect of haemolysis on the hexose monophosphate pathway in normal and in glucose-6-phosphate dehydrogenase-deficient erythrocytes. The hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49) - deficient erythrocytes is under a severe and unexplained restraint (Gaetani, G.D., Parker, J.C. and Kirkman, H.N. (1974) Proc. Natl. Acad. Sci. U.S. 71, 3584-3587). In this study the hexose monophosphate pathway activity and the NADPH level of normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes were measured soon after haemolysis. The results indicate a prompt increase in 14CO2 evolution and a rise in MADPH levels. Since, in this study, the concentration of the haemolysate is comparable to that of intact erythrocytes, the relief of the restraint on glucose-6-phosphate dehydrogenase through dilution-dependent dissociation from inactivator or inhibitor is excluded. The possibility that the intracellular restraint may result from compartmentalization of glucose-6-phosphate dehydrogenase and substrates or from properties of the intact membrane of the erythrocytes is suggested."}
{"id": "PMID:23158", "title": "Proton electrochemical gradient and phosphate potential in submitochondrial particles.", "content": "The aerobic uptake of inorganic ions, such as 86Rb+  or 125I-, by submitochondrial particles, is about one order of magnitude lower than the uptake of organic ions, such as acridines or 8-anilino-1-naphthalene sulphonate. The values of deltapH, the transmembrane pH differential, and deltapsi, the transmembrane membrane potential are between 60 and 100 mV when calculated on the inorganic ions and between 150 and 240 mV when calculated on the organic ions. The discrepancy between the deltapH and deltapsi values from organic and inorganic ions is large at high but not at low ion/protein ratios. 2. In the absence of weak bases and strong acids the values of deltamuH, the proton electrochemical potential difference, are close to 100 mV and the magnitude of deltapH and deltapsi are similar. Weak bases decrease deltapH and enhance deltapsi. Strong acids decrease deltapsi and enhance deltapH. Interchangeability of deltapH with deltapsi occurs at low concentrations of weak bases and strong acids. High concentrations of weak bases and strong acids cause depression of deltamuH. 3. Concentrations of weak bases capable of abolishing deltapH, do not affect ATP synthesis. Concentrations of strong acids capable of abolishing deltapsi affect only slightly ATP synthesis. Concentrations of weak bases and strong acids capable of causing a decline of deltapH + deltapsi inhibit ATP synthesis. 4. Depression of deltamuH is paralleled by inhibition of ATP synthesis and decline of deltaGp, the phosphate potential. Abolition of ATP synthesis occurs only when deltamuH is below 20 mV. The deltaGp/deltamuH ratio increases hyperbolically with the decrease of deltamuH.", "contents": "Proton electrochemical gradient and phosphate potential in submitochondrial particles. The aerobic uptake of inorganic ions, such as 86Rb+  or 125I-, by submitochondrial particles, is about one order of magnitude lower than the uptake of organic ions, such as acridines or 8-anilino-1-naphthalene sulphonate. The values of deltapH, the transmembrane pH differential, and deltapsi, the transmembrane membrane potential are between 60 and 100 mV when calculated on the inorganic ions and between 150 and 240 mV when calculated on the organic ions. The discrepancy between the deltapH and deltapsi values from organic and inorganic ions is large at high but not at low ion/protein ratios. 2. In the absence of weak bases and strong acids the values of deltamuH, the proton electrochemical potential difference, are close to 100 mV and the magnitude of deltapH and deltapsi are similar. Weak bases decrease deltapH and enhance deltapsi. Strong acids decrease deltapsi and enhance deltapH. Interchangeability of deltapH with deltapsi occurs at low concentrations of weak bases and strong acids. High concentrations of weak bases and strong acids cause depression of deltamuH. 3. Concentrations of weak bases capable of abolishing deltapH, do not affect ATP synthesis. Concentrations of strong acids capable of abolishing deltapsi affect only slightly ATP synthesis. Concentrations of weak bases and strong acids capable of causing a decline of deltapH + deltapsi inhibit ATP synthesis. 4. Depression of deltamuH is paralleled by inhibition of ATP synthesis and decline of deltaGp, the phosphate potential. Abolition of ATP synthesis occurs only when deltamuH is below 20 mV. The deltaGp/deltamuH ratio increases hyperbolically with the decrease of deltamuH."}
{"id": "PMID:23159", "title": "Steady-state kinetics of electron transfer through cytochrome chain of uncoupled submitochondrial particles. II. Influence of pH on kinetics of electron transfer.", "content": "pH Dependences of steady-state kinetic parameters of cytochrome chains of submitochondrial particles have been studies. It has been shown that the lifetimes of activated states (tau) of the pairs of cytochromes b leads to c1 and a leads to a3 have different pH dependences; those for the c1 leads to c and c leads to a cytochrome pairs being similar. The rate constants for the non-activated state of the respiratory chains decreased for the b leads to c1 pair and increased for the a leads to a3 pair when the pH value was increased. The values of pK calculated from these dependences for the pairs b leads to c1 and a leads to a3 were 7.2 and 8.9, respectively. It has been supposed that the ratio of activated to non-activated electron carriers may be controlled by the local pH value in the mitochondrial membrane, the latter being dependent upon the rate of electron transfer. The kinetic model based on this assumption allows one to explain the experimental dependences on pH of the rate constants for cytochromes b leads to c, and a leads to a3. The values of the diffusion rate constants for H+ and OH- ions in the mitochondrial membrane estimated from these kinetic data obtained in this study were 10(4)--10(5) s-1 and 10(2)--10(3) s-1, respectively.", "contents": "Steady-state kinetics of electron transfer through cytochrome chain of uncoupled submitochondrial particles. II. Influence of pH on kinetics of electron transfer. pH Dependences of steady-state kinetic parameters of cytochrome chains of submitochondrial particles have been studies. It has been shown that the lifetimes of activated states (tau) of the pairs of cytochromes b leads to c1 and a leads to a3 have different pH dependences; those for the c1 leads to c and c leads to a cytochrome pairs being similar. The rate constants for the non-activated state of the respiratory chains decreased for the b leads to c1 pair and increased for the a leads to a3 pair when the pH value was increased. The values of pK calculated from these dependences for the pairs b leads to c1 and a leads to a3 were 7.2 and 8.9, respectively. It has been supposed that the ratio of activated to non-activated electron carriers may be controlled by the local pH value in the mitochondrial membrane, the latter being dependent upon the rate of electron transfer. The kinetic model based on this assumption allows one to explain the experimental dependences on pH of the rate constants for cytochromes b leads to c, and a leads to a3. The values of the diffusion rate constants for H+ and OH- ions in the mitochondrial membrane estimated from these kinetic data obtained in this study were 10(4)--10(5) s-1 and 10(2)--10(3) s-1, respectively."}
{"id": "PMID:23160", "title": "Some kinetic aspects of the mechanism of hydrolysis of phosphoric acid esters by nonspecific acid phosphatase from Schizosaccharomyces pombe.", "content": "1. The kinetics of the hydrolysis of nitrophenylphosphate by nonspecific acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2.) from Schizosaccharomices pombe was studied. 2. The kinetic parameters, Km and V, were determined as well as the inhibition constants, K1, for the inhibitors, phosphate and fluoride, as a function of pH. 3. The results, interpreted according to the theories of Dixon and Waley indicated the presence of three ionizable groups on the enzyme itself and one on the enzyme-substrate complex. 4. A model of the hydrolysis of phosphoric acid monoesters by the S. pombe acid phosphatase is proposed based on the ionization state of the reactants and on the results of the inhibition by the competitive inhibitors.", "contents": "Some kinetic aspects of the mechanism of hydrolysis of phosphoric acid esters by nonspecific acid phosphatase from Schizosaccharomyces pombe. 1. The kinetics of the hydrolysis of nitrophenylphosphate by nonspecific acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2.) from Schizosaccharomices pombe was studied. 2. The kinetic parameters, Km and V, were determined as well as the inhibition constants, K1, for the inhibitors, phosphate and fluoride, as a function of pH. 3. The results, interpreted according to the theories of Dixon and Waley indicated the presence of three ionizable groups on the enzyme itself and one on the enzyme-substrate complex. 4. A model of the hydrolysis of phosphoric acid monoesters by the S. pombe acid phosphatase is proposed based on the ionization state of the reactants and on the results of the inhibition by the competitive inhibitors."}
{"id": "PMID:23161", "title": "Subunit structure and activity of glyceraldehyde-3-phosphate dehydrogenase from spinach chloroplasts.", "content": "Glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate : NADP+ oxidoreductase (phosphorylating), EC 1.2.1.13) from spinach chloroplasts is a polymeric protein of approx. 600,000 daltons and sodium dodecyl sulphate gel electrophoresis shows that it consists of two subunits of molecular weight 43,000 and 37,000. Comparison of amino acid analyses and tryptic peptide maps indicates that the two subunits have a different primary structure. The native enzyme contains 0.5 mol of NADP+ and 0.5 mol of NAD+ per protomer of 80,000 daltons, no reduced pyridine nucleotides have been detected. Almost complete inactivation is obtained by reaction of two cysteinyl residues per 80,000 daltons with tetrathionate or iodo[14C2]acetic acid; since the same amount of radioactivity is incorporated in the two subunits it is likely that they are both essential for the catalytic activity. Charcoal stripping of native glyceraldehyde-phosphate dehydrogenase produces an apoprotein which still retains most of the enzymatic activity but, unlike the holoenzyme, is gradually inactivated by storage at 4 degrees C and does not react with iodoacetate under the same conditions in which the holoenzyme is completely inactivated.", "contents": "Subunit structure and activity of glyceraldehyde-3-phosphate dehydrogenase from spinach chloroplasts. Glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate : NADP+ oxidoreductase (phosphorylating), EC 1.2.1.13) from spinach chloroplasts is a polymeric protein of approx. 600,000 daltons and sodium dodecyl sulphate gel electrophoresis shows that it consists of two subunits of molecular weight 43,000 and 37,000. Comparison of amino acid analyses and tryptic peptide maps indicates that the two subunits have a different primary structure. The native enzyme contains 0.5 mol of NADP+ and 0.5 mol of NAD+ per protomer of 80,000 daltons, no reduced pyridine nucleotides have been detected. Almost complete inactivation is obtained by reaction of two cysteinyl residues per 80,000 daltons with tetrathionate or iodo[14C2]acetic acid; since the same amount of radioactivity is incorporated in the two subunits it is likely that they are both essential for the catalytic activity. Charcoal stripping of native glyceraldehyde-phosphate dehydrogenase produces an apoprotein which still retains most of the enzymatic activity but, unlike the holoenzyme, is gradually inactivated by storage at 4 degrees C and does not react with iodoacetate under the same conditions in which the holoenzyme is completely inactivated."}
{"id": "PMID:23162", "title": "pH dependence of the kinetic parameters of L-asparaginase.", "content": "The concentration dependence of the rate of hydrolysis of L-asparagine by Escherichia coli L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) has been measured over the range pH 4.5 to pH 9.1 by a direct spectrophotometric assay at 220 nm and by a coupled assay utilizing glutamate dehydrogenase to detect the ammonia produced. The velocity of the hydrolysis reaction at saturating levels of substrate is independent of pH over this interval. The plot of V/km over the same interval is bell-shaped, being dependent on pKa values of 6.58 and 8.69. The higher pKa is attributed to the amino group of asparagine. The lower pKa is associated with the enzyme active site and is probably due to an imidazole group.", "contents": "pH dependence of the kinetic parameters of L-asparaginase. The concentration dependence of the rate of hydrolysis of L-asparagine by Escherichia coli L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) has been measured over the range pH 4.5 to pH 9.1 by a direct spectrophotometric assay at 220 nm and by a coupled assay utilizing glutamate dehydrogenase to detect the ammonia produced. The velocity of the hydrolysis reaction at saturating levels of substrate is independent of pH over this interval. The plot of V/km over the same interval is bell-shaped, being dependent on pKa values of 6.58 and 8.69. The higher pKa is attributed to the amino group of asparagine. The lower pKa is associated with the enzyme active site and is probably due to an imidazole group."}
{"id": "PMID:23163", "title": "Purification and properties of asparagine synthetase from rat liver.", "content": "Asparagine synthetase (L-aspartate:ammonia ligase (AMP-forming, EC 6.3.1.1) activity in rat liver increased when the animals were put on a low casein diet. The enzyme was purified about 280-fold from the supernatant of rat liver homogenate by a procedure comprising ammonium sulfate fractionation. DEAE-Sepharose column chromatography, and Sephadex G-100 gel filtration. The optimal pH of the enzyme was in the range 7.4-7.6 with glutamine as an amide donor. The molecular weight was estimated to be approximately 110,000 by gel filtration. Chloride ion was required for the enzyme activity. The apparent Km values for L-aspartate, L-glutamine, ammonium chloride, ATP, and Cl- were calculated to be 0.76, 4.3, 10, 0.14, and 1.7 mM, respectively. The activity was inhibited by L-asparagine, nucleoside triphosphates except ATP, and sulfhydryl reagents. It has been observed that the properties of asparagine synthetase from rat liver are not so different from those of tumors such as Novikoff hepatoma and RADA 1.", "contents": "Purification and properties of asparagine synthetase from rat liver. Asparagine synthetase (L-aspartate:ammonia ligase (AMP-forming, EC 6.3.1.1) activity in rat liver increased when the animals were put on a low casein diet. The enzyme was purified about 280-fold from the supernatant of rat liver homogenate by a procedure comprising ammonium sulfate fractionation. DEAE-Sepharose column chromatography, and Sephadex G-100 gel filtration. The optimal pH of the enzyme was in the range 7.4-7.6 with glutamine as an amide donor. The molecular weight was estimated to be approximately 110,000 by gel filtration. Chloride ion was required for the enzyme activity. The apparent Km values for L-aspartate, L-glutamine, ammonium chloride, ATP, and Cl- were calculated to be 0.76, 4.3, 10, 0.14, and 1.7 mM, respectively. The activity was inhibited by L-asparagine, nucleoside triphosphates except ATP, and sulfhydryl reagents. It has been observed that the properties of asparagine synthetase from rat liver are not so different from those of tumors such as Novikoff hepatoma and RADA 1."}
{"id": "PMID:23164", "title": "Interaction of steroids with D-amino acid oxidase.", "content": "1. Progesterone inhibited D-amino acid oxidase (D-amino acid : O2 oxidoreductase (deaminating), EC 1.4.3.3) in competition with its substrate, D-alanine. Binding of progesterone brought about the increase in both fluorescence intensity and fluorescence polarization of FAD, which indicates that the environment surrounding FAD chromophore is modified due to a conformational change in the apoenzyme. 2. Ethinyl estradiol, testosterone, testosterone propionate, corticosterone and aldosterone also inhibited the enzyme slightly in the same manner. Their binding also produced a slight increase in FAD fluorescence without decreasing the fluorescence polarization. 3. Cholesterol did not inhibit the enzyme, though it increased the fluorescence polarization of FAD. This indicates the binding of cholesterol with the enzyme at a site other than the substrate binding site.", "contents": "Interaction of steroids with D-amino acid oxidase. 1. Progesterone inhibited D-amino acid oxidase (D-amino acid : O2 oxidoreductase (deaminating), EC 1.4.3.3) in competition with its substrate, D-alanine. Binding of progesterone brought about the increase in both fluorescence intensity and fluorescence polarization of FAD, which indicates that the environment surrounding FAD chromophore is modified due to a conformational change in the apoenzyme. 2. Ethinyl estradiol, testosterone, testosterone propionate, corticosterone and aldosterone also inhibited the enzyme slightly in the same manner. Their binding also produced a slight increase in FAD fluorescence without decreasing the fluorescence polarization. 3. Cholesterol did not inhibit the enzyme, though it increased the fluorescence polarization of FAD. This indicates the binding of cholesterol with the enzyme at a site other than the substrate binding site."}
{"id": "PMID:23165", "title": "Enzymes of the gamma-glutamyl cycle in 'aging' WI-38 fibroblasts and in HeLa S3 cells.", "content": "gamma-Glutamyltransferase ((5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2) activity of WI-38 fibroblasts decreased only slightly in relation to a constant amount of cell-associated protein as the cells were carried in culture serially from middle to late passage numbers leading toward senescence, e.g., from population doubling level 27 through 41. Also, when the enzyme activity was expressed on the basis of a unit number of cells or unit amount of DNA, little change occurred over that range of PDLs. As the culture approached 'phase-out', the transferase activity rose sharply regardless of how the activity was expressed. The possibility is considered that the large increase in activity could be a reflection of a significant increase in size of cells and therefore changes in the membranes where the transferase is located. The occurrence of other enzymes of the 'gamma-glutamyl cycle' in WI-38 and HeLa S3 cells also was demonstrated. These included gamma-glutamylcyclotransferase ((gamma-L-glutamyl)-L-amino-acid gamma-glutamyltransferase (cyclizing), EC 2.3.2.4) and 5-oxoprolinase, whose activities showed no large increase comparable to that of the gamma-glutamyltransferase, as the culture approached 'phase-out'.", "contents": "Enzymes of the gamma-glutamyl cycle in 'aging' WI-38 fibroblasts and in HeLa S3 cells. gamma-Glutamyltransferase ((5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2) activity of WI-38 fibroblasts decreased only slightly in relation to a constant amount of cell-associated protein as the cells were carried in culture serially from middle to late passage numbers leading toward senescence, e.g., from population doubling level 27 through 41. Also, when the enzyme activity was expressed on the basis of a unit number of cells or unit amount of DNA, little change occurred over that range of PDLs. As the culture approached 'phase-out', the transferase activity rose sharply regardless of how the activity was expressed. The possibility is considered that the large increase in activity could be a reflection of a significant increase in size of cells and therefore changes in the membranes where the transferase is located. The occurrence of other enzymes of the 'gamma-glutamyl cycle' in WI-38 and HeLa S3 cells also was demonstrated. These included gamma-glutamylcyclotransferase ((gamma-L-glutamyl)-L-amino-acid gamma-glutamyltransferase (cyclizing), EC 2.3.2.4) and 5-oxoprolinase, whose activities showed no large increase comparable to that of the gamma-glutamyltransferase, as the culture approached 'phase-out'."}
{"id": "PMID:23167", "title": "Tyrosine aminotransferase from chick liver. Heat activation and cold inactivation of the enzyme.", "content": "The reversible heat activation and cold inactivation of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) of chick liver were investigated. When the enzyme obtained by gel filtration was preincubated at 37 degrees C for 10 min with 50 micrometer pyridoxal 5'-phosphate (pyridoxal-5'-P), a 7-fold increase in enzyme activity was detected. When the preincubated enzyme was cooled to 0 degrees C, it lost its activity. Furthermore, the dramatic cyclical changes in enzyme activity occurred by sequential heating at 37 degrees C and cooling to 0 degrees C of the enzyme, in the presence of pyridoxal-5'-P, over shorter periods of time without loss of enzyme activity. However, when alpha-ketoglutarate was added to the enzyme during cold exposure, no further decrease in activity was observed. This protective effect was seen at a concentration of 5 muM.", "contents": "Tyrosine aminotransferase from chick liver. Heat activation and cold inactivation of the enzyme. The reversible heat activation and cold inactivation of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) of chick liver were investigated. When the enzyme obtained by gel filtration was preincubated at 37 degrees C for 10 min with 50 micrometer pyridoxal 5'-phosphate (pyridoxal-5'-P), a 7-fold increase in enzyme activity was detected. When the preincubated enzyme was cooled to 0 degrees C, it lost its activity. Furthermore, the dramatic cyclical changes in enzyme activity occurred by sequential heating at 37 degrees C and cooling to 0 degrees C of the enzyme, in the presence of pyridoxal-5'-P, over shorter periods of time without loss of enzyme activity. However, when alpha-ketoglutarate was added to the enzyme during cold exposure, no further decrease in activity was observed. This protective effect was seen at a concentration of 5 muM."}
{"id": "PMID:23168", "title": "Synthesis of acyl phosphatidylglycerol from phosphatidylglycerol in Escherichia coli K-12. Evidence for the participation of detergent-resistant phospholipase A and heat-labile membrane-bound factor(s).", "content": "The conversion of phosphatidylglycerol to acyl phosphatidylglycerol by extracts of Escherichia coli K-12 strains was examined under various conditions. The maximum rate of conversion was observed at pH 7.2 in the presence of 50% (v/v) diethyl ether and 10 mM CaCl2. This conversion was found to involve two sequential reactions: (1) The formation of 2-acyl glycerophosphoglycerol and 2-acyl glycerophosphoethanolamine from phosphatidylglycerol and phosphatidylethanolamine, respectively, by detergent-resistant phospholipase A in the presence of Ca2+ and (2) transfer of the acyl group of 2-acyl lysophospholipid to phosphatidylglycerol by a heat-labile factor(s) in the presence of diethyl ether. Neither fatty, acid acyl-CoA nor 1-acyl lysophospholipid could act as an acyl donor for phosphatidylglycerol. The heat-labile factor(s) was found in both the inner membrane and supernatant fractions.", "contents": "Synthesis of acyl phosphatidylglycerol from phosphatidylglycerol in Escherichia coli K-12. Evidence for the participation of detergent-resistant phospholipase A and heat-labile membrane-bound factor(s). The conversion of phosphatidylglycerol to acyl phosphatidylglycerol by extracts of Escherichia coli K-12 strains was examined under various conditions. The maximum rate of conversion was observed at pH 7.2 in the presence of 50% (v/v) diethyl ether and 10 mM CaCl2. This conversion was found to involve two sequential reactions: (1) The formation of 2-acyl glycerophosphoglycerol and 2-acyl glycerophosphoethanolamine from phosphatidylglycerol and phosphatidylethanolamine, respectively, by detergent-resistant phospholipase A in the presence of Ca2+ and (2) transfer of the acyl group of 2-acyl lysophospholipid to phosphatidylglycerol by a heat-labile factor(s) in the presence of diethyl ether. Neither fatty, acid acyl-CoA nor 1-acyl lysophospholipid could act as an acyl donor for phosphatidylglycerol. The heat-labile factor(s) was found in both the inner membrane and supernatant fractions."}
{"id": "PMID:23169", "title": "Cyclic peroxides from a soya lipoxygenase-catalysed oxygenation of methyl linolenate.", "content": "Incubation of methyl linolenate with an aqueous extract of soyabean flour at neutral pH gives the hydroperoxyendoperoxides 16-hydroxyperoxy-13,15-endoperoxylinolenate and 9-hydroxyperoxy-10,12-endoperoxylinolenate as the principal oxygenation products in addition to monohydroperoxides. Lipoxygenase I (EC 1.13.11.12) does not catalyse the oxygenation under this condition. The enzyme contributing most to the formation of the hydroperoxyendoperoxides is assumed to be a high molecular mass lipoxygenase aggregate.", "contents": "Cyclic peroxides from a soya lipoxygenase-catalysed oxygenation of methyl linolenate. Incubation of methyl linolenate with an aqueous extract of soyabean flour at neutral pH gives the hydroperoxyendoperoxides 16-hydroxyperoxy-13,15-endoperoxylinolenate and 9-hydroxyperoxy-10,12-endoperoxylinolenate as the principal oxygenation products in addition to monohydroperoxides. Lipoxygenase I (EC 1.13.11.12) does not catalyse the oxygenation under this condition. The enzyme contributing most to the formation of the hydroperoxyendoperoxides is assumed to be a high molecular mass lipoxygenase aggregate."}
{"id": "PMID:23171", "title": "Evidence for the different responses of delta9-, delta6- and delta5-fatty acyl-CoA desaturases to cytoplasmic proteins.", "content": "Microsomes prepared from the livers of 4-week-old rats were, after extraction with 0.1 M potassium phosphate buffer, pH 7.4, unable to catalyse either the delta6 desaturation of alpha-linolenic acid (9c.12c.15c., 18 : 3) into 6c.9c.12c.15c., 18 : 4 or the delta5 desaturation of eicosatrienoic acid (8c.11c.14c., 20 : 3) into arachidonic acid (5c.8c.11c.14c., 20 : 4). Both these enzymes only showed full activity after incubation of the microsomes with either the 100 000 X g supernatant fraction or with purified bovine catalase. Bovine serum albumin, while capable of restoring 50% of the delta5 desaturase activity has no effect on the delta6 desaturase. In contrast the delta9 desaturase activity of microsomes was never completely lost after extraction with buffer but could be stimulated by optimum concentrations of both bovine serum albumin and catalase. The significance of the different responses of the three desaturases to the cytoplasmic components is discussed.", "contents": "Evidence for the different responses of delta9-, delta6- and delta5-fatty acyl-CoA desaturases to cytoplasmic proteins. Microsomes prepared from the livers of 4-week-old rats were, after extraction with 0.1 M potassium phosphate buffer, pH 7.4, unable to catalyse either the delta6 desaturation of alpha-linolenic acid (9c.12c.15c., 18 : 3) into 6c.9c.12c.15c., 18 : 4 or the delta5 desaturation of eicosatrienoic acid (8c.11c.14c., 20 : 3) into arachidonic acid (5c.8c.11c.14c., 20 : 4). Both these enzymes only showed full activity after incubation of the microsomes with either the 100 000 X g supernatant fraction or with purified bovine catalase. Bovine serum albumin, while capable of restoring 50% of the delta5 desaturase activity has no effect on the delta6 desaturase. In contrast the delta9 desaturase activity of microsomes was never completely lost after extraction with buffer but could be stimulated by optimum concentrations of both bovine serum albumin and catalase. The significance of the different responses of the three desaturases to the cytoplasmic components is discussed."}
{"id": "PMID:23172", "title": "Determination of lipoprotein-lipase activity in human skeletal muscle tissue.", "content": "An in vitro assay system was developed for the determination of lipoprotein-lipase activity in 10--30-mg specimens of human skeletal muscle tissue. The reaction medium of the assay was based on a glycine buffer of pH 8.3 (at 37 degrees C) with a heparin concentration of 1.5 g/l (about 180 IU/ml). The enzyme activity was measured as the release of [3H]oleic acid from a serum-activated, triglyceride emulsion, in which [3H]trioleate was used as trace substance. The enzyme activity studied had the characteristic properties of lipoprotein-lipase activity, i.e. it was activated by the addition of serum or apolipoprotein C-II and inhibited in the presence of high ionic strength, protamine sulphate or apolipoprotein C-III. A mean Km of 0.40 +/- 0.13 (S.D.) mmol/l for triglyceride substrate was found in tissue samples that had very different concentrations of lipoprotein-lipase activity. This Km was similar to the low fasting concentrations of very low density lipoprotein triglycerides often found in healthy individuals. The lipoprotein-lipase activity was not decreased freezing and storing the tissue specimens in liquid nitrogen. The within-day variation of the method was 16 percent and the between-day variation 8 percent. Muscle tissue from the vastus lateralis muscle had, on the average, a 60 percent higher concentration of lipoprotein-lipase activity than the rectus abdominis muscle in the same subject.", "contents": "Determination of lipoprotein-lipase activity in human skeletal muscle tissue. An in vitro assay system was developed for the determination of lipoprotein-lipase activity in 10--30-mg specimens of human skeletal muscle tissue. The reaction medium of the assay was based on a glycine buffer of pH 8.3 (at 37 degrees C) with a heparin concentration of 1.5 g/l (about 180 IU/ml). The enzyme activity was measured as the release of [3H]oleic acid from a serum-activated, triglyceride emulsion, in which [3H]trioleate was used as trace substance. The enzyme activity studied had the characteristic properties of lipoprotein-lipase activity, i.e. it was activated by the addition of serum or apolipoprotein C-II and inhibited in the presence of high ionic strength, protamine sulphate or apolipoprotein C-III. A mean Km of 0.40 +/- 0.13 (S.D.) mmol/l for triglyceride substrate was found in tissue samples that had very different concentrations of lipoprotein-lipase activity. This Km was similar to the low fasting concentrations of very low density lipoprotein triglycerides often found in healthy individuals. The lipoprotein-lipase activity was not decreased freezing and storing the tissue specimens in liquid nitrogen. The within-day variation of the method was 16 percent and the between-day variation 8 percent. Muscle tissue from the vastus lateralis muscle had, on the average, a 60 percent higher concentration of lipoprotein-lipase activity than the rectus abdominis muscle in the same subject."}
{"id": "PMID:23173", "title": "The activator of cerebroside-sulphatase. A model of the activation.", "content": "The activator of cereboroside-sulphatase (cerebroside-3-sulphate-3-sulphohydrolase, EC 3.1.6.8) is necessary for the enzymic hydrolysis of sulphatides (cerebroside sulphates) at ionic concentrations in the physiological range. The pH optimum of the reaction is 4.5--4.8. Under similar incubation conditions, a complex is formed between activator and sulphatides which is partially inhibited, due to competitive binding in the presence of cerebrosides of phosphatidylserine. Inhibition depends upon the concentration of the lipids and is of the same order of magnitude as the inhibition (by these lipids) of enzymic sulphatide hydrolysis in the presence of activator. Complex formation between activator and sulphatides is reversible since the complex dissociates partially when certain concentrations of phosphatidylserine are added. Moreover, the rate of sulphatide hydrolysis increases with the concentration of the activator.sulphatide complex in the reaction mixture. This indicates that the activator.sulphatide complex is the substrate for the enzyme and a model for this activation is presented.", "contents": "The activator of cerebroside-sulphatase. A model of the activation. The activator of cereboroside-sulphatase (cerebroside-3-sulphate-3-sulphohydrolase, EC 3.1.6.8) is necessary for the enzymic hydrolysis of sulphatides (cerebroside sulphates) at ionic concentrations in the physiological range. The pH optimum of the reaction is 4.5--4.8. Under similar incubation conditions, a complex is formed between activator and sulphatides which is partially inhibited, due to competitive binding in the presence of cerebrosides of phosphatidylserine. Inhibition depends upon the concentration of the lipids and is of the same order of magnitude as the inhibition (by these lipids) of enzymic sulphatide hydrolysis in the presence of activator. Complex formation between activator and sulphatides is reversible since the complex dissociates partially when certain concentrations of phosphatidylserine are added. Moreover, the rate of sulphatide hydrolysis increases with the concentration of the activator.sulphatide complex in the reaction mixture. This indicates that the activator.sulphatide complex is the substrate for the enzyme and a model for this activation is presented."}
{"id": "PMID:23174", "title": "Some effects of glucose concentration and anoxia on glycolysis and metabolite concentrations in the perfused liver of fetal guinea pig.", "content": "Effects of glucose concentration and anoxia upon the metabolite concentrations and rates of glycolysis and respiration have been investigated in the perfused liver of the fetal guinea pig. In most cases the metabolite concentrations in the perfused liver were similar to those observed in vivo. Between 50 days and term there was a fall in the respiratory rate and in the concentration of ATP and fructose 1,6-diphosphate and an increase in the concentration of glutamate, glycogen and glucose. Reducing the medium glucose concentration from 10 mM to 1 mM or 0.1 mM depressed lactate production and the concentration of most of the phosphorylated intermediates (except 6-phosphogluconate) in the liver of the 50-day fetus. This indicates a fall in glycolytic rate which is not in accord with the known kinetic properties of hexokinase in the fetal liver. Anoxia increased lactate production by, and the concentrations of, the hexose phosphates ADP and AMP in the 50-day to term fetal liver, while the concentration of ribulose 5-phosphate, ATP and some triose phosphates fell. These results are consistent with an activation of glycolysis, particularly at phosphofructokinase and of a reduction in pentose phosphate pathway activity, particularly at 6-phosphogluconate dehydrogenase. The calculated cytosolic NAD+/NADH ratio for the perfused liver was similar to that measured in vivo and evidence is presented to suggest that the dihydroxyacetone phosphate/glycerol 3-phosphate ratio gives a better indication of cytosolic redox than the lactate/pyruvate ratio. The present observations indicate that phosphofructokinase hexokinase and possibly pyruvate kinase control the glycolytic rate and that glyceraldehyde-3-phosphate dehydrogenase is at equilibrium in the perfused liver of the fetal guinea pig.", "contents": "Some effects of glucose concentration and anoxia on glycolysis and metabolite concentrations in the perfused liver of fetal guinea pig. Effects of glucose concentration and anoxia upon the metabolite concentrations and rates of glycolysis and respiration have been investigated in the perfused liver of the fetal guinea pig. In most cases the metabolite concentrations in the perfused liver were similar to those observed in vivo. Between 50 days and term there was a fall in the respiratory rate and in the concentration of ATP and fructose 1,6-diphosphate and an increase in the concentration of glutamate, glycogen and glucose. Reducing the medium glucose concentration from 10 mM to 1 mM or 0.1 mM depressed lactate production and the concentration of most of the phosphorylated intermediates (except 6-phosphogluconate) in the liver of the 50-day fetus. This indicates a fall in glycolytic rate which is not in accord with the known kinetic properties of hexokinase in the fetal liver. Anoxia increased lactate production by, and the concentrations of, the hexose phosphates ADP and AMP in the 50-day to term fetal liver, while the concentration of ribulose 5-phosphate, ATP and some triose phosphates fell. These results are consistent with an activation of glycolysis, particularly at phosphofructokinase and of a reduction in pentose phosphate pathway activity, particularly at 6-phosphogluconate dehydrogenase. The calculated cytosolic NAD+/NADH ratio for the perfused liver was similar to that measured in vivo and evidence is presented to suggest that the dihydroxyacetone phosphate/glycerol 3-phosphate ratio gives a better indication of cytosolic redox than the lactate/pyruvate ratio. The present observations indicate that phosphofructokinase hexokinase and possibly pyruvate kinase control the glycolytic rate and that glyceraldehyde-3-phosphate dehydrogenase is at equilibrium in the perfused liver of the fetal guinea pig."}
{"id": "PMID:23175", "title": "A specific gastrin receptor site in the rat stomach.", "content": "A specific receptor for gastrin I has been demonstrated in the rat stomach fundus. Specific binding of 125I-labelled gastrin I was localised to particles sedimenting between 250--20 000 X g. Saturation of binding sites occurred with a gastrin concentration of 10(-11) M in an assay system containing 0.6--1.7 mg/ml of homogenate protein. Gastrin binding was shown to be reversible, temperature- and pH-dependent, and susceptible to tryptic digestion. Electron microscopic and enzymatic studies showed the binding fraction to contain predominantly mitochondria. Preincubation of the homogenate with 10(-8) M cholecystokinin or secretin inhibited gastrin binding to a greater extent than an equimolar concentration of pentagastrin. Cimetidine, a histamine receptor antagonist, did not affect binding of gastrin to the receptor.", "contents": "A specific gastrin receptor site in the rat stomach. A specific receptor for gastrin I has been demonstrated in the rat stomach fundus. Specific binding of 125I-labelled gastrin I was localised to particles sedimenting between 250--20 000 X g. Saturation of binding sites occurred with a gastrin concentration of 10(-11) M in an assay system containing 0.6--1.7 mg/ml of homogenate protein. Gastrin binding was shown to be reversible, temperature- and pH-dependent, and susceptible to tryptic digestion. Electron microscopic and enzymatic studies showed the binding fraction to contain predominantly mitochondria. Preincubation of the homogenate with 10(-8) M cholecystokinin or secretin inhibited gastrin binding to a greater extent than an equimolar concentration of pentagastrin. Cimetidine, a histamine receptor antagonist, did not affect binding of gastrin to the receptor."}
{"id": "PMID:23176", "title": "Effects of fatty acids on superoxide radical generation in leukocytes.", "content": "Acetylated ferricytochrome c was employed for the detection of superoxide radicals (O-2) generated both in intact cells and in subcellular fractions of leukocytes. Certain saturated fatty acids, myristate in particular, induced the production of O-2 in leukocytes, suggesting a correlation between the formation of O-2 and the hydrophobic interaction of fatty acids with the leukocyte plasma membrane. As compared with O-2 radical generation from phagocytizing leukocytes a greater stimulation of O-2 formation was observed in cells in which myristate was added. The enhanced activity which generated O-2 in the cell-free system was located in a particulate fraction but not in the cytosol. The rate of O-2 generation in the particulate fraction was higher in the presence of NADPH than in the presence of NADH. The effects of reagents such as KCN, 2,4-dichlorophenol and aminotriazole on the O-2 generation in this fraction are examined and the nature of the O-2 generating system is discussed.", "contents": "Effects of fatty acids on superoxide radical generation in leukocytes. Acetylated ferricytochrome c was employed for the detection of superoxide radicals (O-2) generated both in intact cells and in subcellular fractions of leukocytes. Certain saturated fatty acids, myristate in particular, induced the production of O-2 in leukocytes, suggesting a correlation between the formation of O-2 and the hydrophobic interaction of fatty acids with the leukocyte plasma membrane. As compared with O-2 radical generation from phagocytizing leukocytes a greater stimulation of O-2 formation was observed in cells in which myristate was added. The enhanced activity which generated O-2 in the cell-free system was located in a particulate fraction but not in the cytosol. The rate of O-2 generation in the particulate fraction was higher in the presence of NADPH than in the presence of NADH. The effects of reagents such as KCN, 2,4-dichlorophenol and aminotriazole on the O-2 generation in this fraction are examined and the nature of the O-2 generating system is discussed."}
{"id": "PMID:23177", "title": "Interferon suppresses steroid-inducible glutamine synthetase biosynthesis in embryonic chick neural retina.", "content": "Effect of chick interferon on the biosynthesis of glutamine synthetase (L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2) was studied in the embryonic chick neural retina cultures induced for the enzyme activity by hydrocortisone. The retinal enzyme radioactively labelled with [3H]leucine was precipitated by specific antibody against the enzyme isolated from adult chick liver. The immunological determination offered evidence that the suppressive effect of interferon on the hormonal induction of the enzyme was primarily due to reduced rate of its synthesis and accumulation.", "contents": "Interferon suppresses steroid-inducible glutamine synthetase biosynthesis in embryonic chick neural retina. Effect of chick interferon on the biosynthesis of glutamine synthetase (L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2) was studied in the embryonic chick neural retina cultures induced for the enzyme activity by hydrocortisone. The retinal enzyme radioactively labelled with [3H]leucine was precipitated by specific antibody against the enzyme isolated from adult chick liver. The immunological determination offered evidence that the suppressive effect of interferon on the hormonal induction of the enzyme was primarily due to reduced rate of its synthesis and accumulation."}
{"id": "PMID:23179", "title": "The role of ammonia, L-glutamate, and cyclic adenosine 3',5'-monophosphate in the regulation of ammonia assimilation in Rhizobium japonicum.", "content": "The effects of three factors (ammonia, L-glutamate, and cyclic adenosine 3',5'-monophosphate) on the ammonia assimilatory processes in aerobically grown Rhizobium japonicum colony derivatives were examined. Ammonia repressed glutamine synthetase activity and increased the average state of adenylylation of this enzyme. The addition of L-glutamate drastically decreased growth and strongly repressed glutamate synthase levels. Glutamine synthetase repression and adenylylation state were also increased by L-glutamate. The presence of cyclic AMP led to the repression of all three NH+4 assimilatory enzymes.", "contents": "The role of ammonia, L-glutamate, and cyclic adenosine 3',5'-monophosphate in the regulation of ammonia assimilation in Rhizobium japonicum. The effects of three factors (ammonia, L-glutamate, and cyclic adenosine 3',5'-monophosphate) on the ammonia assimilatory processes in aerobically grown Rhizobium japonicum colony derivatives were examined. Ammonia repressed glutamine synthetase activity and increased the average state of adenylylation of this enzyme. The addition of L-glutamate drastically decreased growth and strongly repressed glutamate synthase levels. Glutamine synthetase repression and adenylylation state were also increased by L-glutamate. The presence of cyclic AMP led to the repression of all three NH+4 assimilatory enzymes."}
{"id": "PMID:23180", "title": "The proteolytic system of Penicillium roqueforti. V. -- Purification and properties of an alkaline aminopeptidase.", "content": "An alkaline aminopeptidase was isolated from the culture medium of Penicillium roqueforti. The enzyme was purified by ammonium sulfate precipitation, filtration on Bio-Gel P-100, chromatography on D.E.A.E.-cellulose and hydroxylapatite, filtration on Bio-Gel P-150 and electrofusing. The purified preparation was homogeneous on polyacrylamide gel electrophoresis at pH 8.5. The molecular weight of the enzyme was estimated to be about 35,000 daltons. The isoelectric point is 4.5. The optimum pH for L-leucine-p-nitroanilide hydrolysis is 8.0. At 35 degrees C the enzyme is stable between pH 6.0 and 7.0. Ethylenediamine tetraacetic acid and a sulfhydryl reagent (p-hydroxymercuribenzoate) inhibit the activity, but the enzyme is insensitive to diisopropylfluorophosphate. Hydrolysis of synthetic peptides shows that the enzyme releases apolar amino acids. Dipeptides are poorly hydrolyzed and Gly in penultimate or N-terminal position causes poor activity. The enzyme is able to cleave the N-terminal Arg-Pro bond of bradykinin.", "contents": "The proteolytic system of Penicillium roqueforti. V. -- Purification and properties of an alkaline aminopeptidase. An alkaline aminopeptidase was isolated from the culture medium of Penicillium roqueforti. The enzyme was purified by ammonium sulfate precipitation, filtration on Bio-Gel P-100, chromatography on D.E.A.E.-cellulose and hydroxylapatite, filtration on Bio-Gel P-150 and electrofusing. The purified preparation was homogeneous on polyacrylamide gel electrophoresis at pH 8.5. The molecular weight of the enzyme was estimated to be about 35,000 daltons. The isoelectric point is 4.5. The optimum pH for L-leucine-p-nitroanilide hydrolysis is 8.0. At 35 degrees C the enzyme is stable between pH 6.0 and 7.0. Ethylenediamine tetraacetic acid and a sulfhydryl reagent (p-hydroxymercuribenzoate) inhibit the activity, but the enzyme is insensitive to diisopropylfluorophosphate. Hydrolysis of synthetic peptides shows that the enzyme releases apolar amino acids. Dipeptides are poorly hydrolyzed and Gly in penultimate or N-terminal position causes poor activity. The enzyme is able to cleave the N-terminal Arg-Pro bond of bradykinin."}
{"id": "PMID:23182", "title": "[Photosynthetic electron transfer at the level of cytochrome f and plastocyanin].", "content": "Light-induced redox conversions of cytochrome f and plastocyanin in situ and electron transporst from H2O to NADP+ were studied by a dual-wave differential spectrophotometry under identical conditions and subsequently compared. The analysis in red and far red light, treatment by inhibitors, e. g. diurone and dibromothymoquinone, and the analysis of photoreactions during the greening of etiolated seedlings demonstrated that cytochrome f functions only in the non-cyclic chain of electron transport, whereas plastocyanin--both in the non-cyclic and in the cyclic electron transport chains. The jositions of cytochrome f and plastocyanin in various electron-transport chains are proposed.", "contents": "[Photosynthetic electron transfer at the level of cytochrome f and plastocyanin]. Light-induced redox conversions of cytochrome f and plastocyanin in situ and electron transporst from H2O to NADP+ were studied by a dual-wave differential spectrophotometry under identical conditions and subsequently compared. The analysis in red and far red light, treatment by inhibitors, e. g. diurone and dibromothymoquinone, and the analysis of photoreactions during the greening of etiolated seedlings demonstrated that cytochrome f functions only in the non-cyclic chain of electron transport, whereas plastocyanin--both in the non-cyclic and in the cyclic electron transport chains. The jositions of cytochrome f and plastocyanin in various electron-transport chains are proposed."}
{"id": "PMID:23183", "title": "[Kinetic study of the pH-dependence of maximal rate of Ca-ATP hydrolysis by myosin].", "content": "Curves of V pH-dependence for Ca ATPase of myosin and heavy meromyosin are demonstrated to be well modelled with theoretical curves for the case of proton dissociation at three groups of enzyme-substrate complex with the loss of the activity at some intermediate ionization stage. Variation of pK values for these three groups and the degree of inhibition for intermediate forms of enzyme-substrate complex are found to be sufficient to reproduce main varieties of described in the literature and obtained in this work multiformity of pH-dependence curves of different nucleoside triphosphates hydrolysis by both native and modified enzymes. Calculated pK values and modification data suggest a significant importance of the dissociation of two imidazole groups (\"activating\" and \"inhibitory\") and cisteine sulhydryl group for the catalytic activity of myosin. Inhibition of ATPase activity by increasing of KCl concentrations is found to be due first of all to a shift in pK values of \"inhibitory\" imidazole and sulhydryl groups.", "contents": "[Kinetic study of the pH-dependence of maximal rate of Ca-ATP hydrolysis by myosin]. Curves of V pH-dependence for Ca ATPase of myosin and heavy meromyosin are demonstrated to be well modelled with theoretical curves for the case of proton dissociation at three groups of enzyme-substrate complex with the loss of the activity at some intermediate ionization stage. Variation of pK values for these three groups and the degree of inhibition for intermediate forms of enzyme-substrate complex are found to be sufficient to reproduce main varieties of described in the literature and obtained in this work multiformity of pH-dependence curves of different nucleoside triphosphates hydrolysis by both native and modified enzymes. Calculated pK values and modification data suggest a significant importance of the dissociation of two imidazole groups (\"activating\" and \"inhibitory\") and cisteine sulhydryl group for the catalytic activity of myosin. Inhibition of ATPase activity by increasing of KCl concentrations is found to be due first of all to a shift in pK values of \"inhibitory\" imidazole and sulhydryl groups."}
{"id": "PMID:23185", "title": "Blockade by psychotropic drugs of the muscarinic acetylcholine receptor in cultured nerve cells.", "content": "The ability of antimuscarinics, tricyclic antidepressants, and antipsychotics to block the muscarinic acetylcholine receptor was determined using an assay for this receptor in cultured nerve cells. The technique involved the assay of receptor-mediated formation of guanosine 3',5'-cyclic phosphate (cyclic GMP) from radioactively labeled guanosine 5'-triphosphate in living mouse neuroblastoma cells (clone N1E-115). This cyclic GMP formation occurred rapidly (peak at 30 sec) and was dependent on the concentration of agonist. The psychotropic drugs tested blocked the muscarinic receptor and equilibrium dissociation constants (KB) were calculated from the parallel displacement of dose-response curves. The most potent compound was the antimuscarinic dexetimide (KB= 5 X 10(-11) M); while the least potent was the antipsychotic prochlorperzine (KB=4X10(-5) M). All tricyclic antidepressants with tertiary amine side chains were more potent (2-20 times) than those with secondary amine side chains; whereas phenothiazine potency correlated with the side chain structure as follows: piperadine greater than alkylamine greater than or equal to piperazine. These data for psychotherapeutic drugs may have direct clinical application.", "contents": "Blockade by psychotropic drugs of the muscarinic acetylcholine receptor in cultured nerve cells. The ability of antimuscarinics, tricyclic antidepressants, and antipsychotics to block the muscarinic acetylcholine receptor was determined using an assay for this receptor in cultured nerve cells. The technique involved the assay of receptor-mediated formation of guanosine 3',5'-cyclic phosphate (cyclic GMP) from radioactively labeled guanosine 5'-triphosphate in living mouse neuroblastoma cells (clone N1E-115). This cyclic GMP formation occurred rapidly (peak at 30 sec) and was dependent on the concentration of agonist. The psychotropic drugs tested blocked the muscarinic receptor and equilibrium dissociation constants (KB) were calculated from the parallel displacement of dose-response curves. The most potent compound was the antimuscarinic dexetimide (KB= 5 X 10(-11) M); while the least potent was the antipsychotic prochlorperzine (KB=4X10(-5) M). All tricyclic antidepressants with tertiary amine side chains were more potent (2-20 times) than those with secondary amine side chains; whereas phenothiazine potency correlated with the side chain structure as follows: piperadine greater than alkylamine greater than or equal to piperazine. These data for psychotherapeutic drugs may have direct clinical application."}
{"id": "PMID:23187", "title": "A study of the oxygenation of trochanteric bone blood and its correlation with the maximum intra-medullary pressure value in 85 cases of chronic coxopathy.", "content": "The authors carried out measurements of the gases (pH, PCO2, PO2, SaO2) on blood from the trochanter of 85 chronic hip diseases in 73 patients. Simultaneous measurements were made on the arterial blood and on the blood of the femoral vein of the same side. A statistically significant difference in blood PO2 and oxygen saturation between the group of necrosis of the femoral head and the group of osteoarthritic hips was found. There is a paradoxical oxygen hypersaturation in case of necrosis. This hypersaturation is observed to parallel the increase of the intramedullary pressure in the same bone area.", "contents": "A study of the oxygenation of trochanteric bone blood and its correlation with the maximum intra-medullary pressure value in 85 cases of chronic coxopathy. The authors carried out measurements of the gases (pH, PCO2, PO2, SaO2) on blood from the trochanter of 85 chronic hip diseases in 73 patients. Simultaneous measurements were made on the arterial blood and on the blood of the femoral vein of the same side. A statistically significant difference in blood PO2 and oxygen saturation between the group of necrosis of the femoral head and the group of osteoarthritic hips was found. There is a paradoxical oxygen hypersaturation in case of necrosis. This hypersaturation is observed to parallel the increase of the intramedullary pressure in the same bone area."}
{"id": "PMID:23188", "title": "[Detection of a new anomalous variant of glucose-6-phosphate dehydrogenase in human erythrocytes].", "content": "Kinetic and electrophoretic properties of 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G6PD) from red cells of donors and patients with acute drug hemolytic anemia due to G6PD deficiency were studied. A new abnormal variant of G6PD isolated from red cell of a patient with acute drug hemolytic anemia, which was not described in literature, has been discovered. The abnormal enzyme differs from the normal by decreased Michaelis constant for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (NADP), by increased utilization of analogues of substrates--2-deoxy-glucose-6-phosphate and particularly deamino-NADP, by low thermal stability, by the character of pH-dependence, by the appearance of a single band of G6PD activity in polyacrylamide gel electrophoresis.", "contents": "[Detection of a new anomalous variant of glucose-6-phosphate dehydrogenase in human erythrocytes]. Kinetic and electrophoretic properties of 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G6PD) from red cells of donors and patients with acute drug hemolytic anemia due to G6PD deficiency were studied. A new abnormal variant of G6PD isolated from red cell of a patient with acute drug hemolytic anemia, which was not described in literature, has been discovered. The abnormal enzyme differs from the normal by decreased Michaelis constant for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (NADP), by increased utilization of analogues of substrates--2-deoxy-glucose-6-phosphate and particularly deamino-NADP, by low thermal stability, by the character of pH-dependence, by the appearance of a single band of G6PD activity in polyacrylamide gel electrophoresis."}
{"id": "PMID:23191", "title": "The beta-adrenoceptor stimulant properties of OPC-2009 on guinea-pig isolated tracheal, right atrial and left atrial preparations.", "content": "1. The beta-adrenoceptor stimulant properties of 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxy-carbostyril hydrochloride hemihydrate (OPC-2009) were compared with those of isoprenaline and salbutamol on guinea-pig isolated tissues. 2. In producing tracheal relaxation, OPC-2009 was approximately 7 times more potent and salbutamol 5 times less potent than isoprenaline. Both compounds were less potent than isoprenaline in increasing either the rate of beating of isolated right atria or the contractile force of left atria, OPC-2009 being 4 and 127 times and salbutamol being 100 and 700 times less potent on the respective preparations. 3. Selectivity calculated from EC50 ratio indicates that OPC-2009 was approximately 26 times and salbutamol approximately 21 times more selective than isoprenaline for tracheal smooth muscle as compared to right atrial muscle, whereas OPC-2009 was approximately 850 times and salbutamol 140 times more selective than isoprenaline for tracheal smooth muscle as compared to left atria. 4. The responses to OPC-2009 on trachea and right atria were not altered by treatment of animals with reserpine 24 h previously. Propranolol was a competitive antagonist of OPC-2009 on these tissues. 5. OPC-2009 at high concentrations competitively antagonized the positive chronotropic and inotropic responses to isoprenaline, indicating that OPC-2009 like salbutamol, may be classified as a partial agonist. 6. The results indicate that the action of OPC-2009 is more selective for tracheal smooth muscle than cardiac muscle and are interpreted in the light of subdivisions of beta-adrenoceptors.", "contents": "The beta-adrenoceptor stimulant properties of OPC-2009 on guinea-pig isolated tracheal, right atrial and left atrial preparations. 1. The beta-adrenoceptor stimulant properties of 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxy-carbostyril hydrochloride hemihydrate (OPC-2009) were compared with those of isoprenaline and salbutamol on guinea-pig isolated tissues. 2. In producing tracheal relaxation, OPC-2009 was approximately 7 times more potent and salbutamol 5 times less potent than isoprenaline. Both compounds were less potent than isoprenaline in increasing either the rate of beating of isolated right atria or the contractile force of left atria, OPC-2009 being 4 and 127 times and salbutamol being 100 and 700 times less potent on the respective preparations. 3. Selectivity calculated from EC50 ratio indicates that OPC-2009 was approximately 26 times and salbutamol approximately 21 times more selective than isoprenaline for tracheal smooth muscle as compared to right atrial muscle, whereas OPC-2009 was approximately 850 times and salbutamol 140 times more selective than isoprenaline for tracheal smooth muscle as compared to left atria. 4. The responses to OPC-2009 on trachea and right atria were not altered by treatment of animals with reserpine 24 h previously. Propranolol was a competitive antagonist of OPC-2009 on these tissues. 5. OPC-2009 at high concentrations competitively antagonized the positive chronotropic and inotropic responses to isoprenaline, indicating that OPC-2009 like salbutamol, may be classified as a partial agonist. 6. The results indicate that the action of OPC-2009 is more selective for tracheal smooth muscle than cardiac muscle and are interpreted in the light of subdivisions of beta-adrenoceptors."}
{"id": "PMID:23189", "title": "The action of hypercapnia during hypoxia on pulmonary vessels.", "content": "Two opposing actions of CO2 on pulmonary vessels, vasoconstriction and vasodilatation, were studied in dogs, cats, ferrets and rats using isolated lungs or a lobe of lung in vivo. Both preparations were perfused at a constant flow rate so that changes in inflow pressure at constant outflow pressure represented changes in vascular resistance. Lungs were ventilated with 5-15 percent CO2 during hypoxic vasoconstriction in order to permit demonstration of dilatation and because the two stimuli frequently concur. During hypoxia CO2 caused further constriction, dilatation or a biphasic response. Only constriction occurred in dogs and only dilatation in rats. Constriction predominated in cats but dilatation sometimes occurred in later tests in isolated lungs and after a carbonic anhydrase inhibitor. All three responses were seen in ferrets. The type of response did not depend on CO2 concentration. In rats dilatation turned to constriction after beta-adrenoreceptor blocking drugs. The vessels affected by dilatation could not be determined. Thus CO2 can enhance or diminish the action of hypoxia but the circumstances determining one or other action are not resolved.", "contents": "The action of hypercapnia during hypoxia on pulmonary vessels. Two opposing actions of CO2 on pulmonary vessels, vasoconstriction and vasodilatation, were studied in dogs, cats, ferrets and rats using isolated lungs or a lobe of lung in vivo. Both preparations were perfused at a constant flow rate so that changes in inflow pressure at constant outflow pressure represented changes in vascular resistance. Lungs were ventilated with 5-15 percent CO2 during hypoxic vasoconstriction in order to permit demonstration of dilatation and because the two stimuli frequently concur. During hypoxia CO2 caused further constriction, dilatation or a biphasic response. Only constriction occurred in dogs and only dilatation in rats. Constriction predominated in cats but dilatation sometimes occurred in later tests in isolated lungs and after a carbonic anhydrase inhibitor. All three responses were seen in ferrets. The type of response did not depend on CO2 concentration. In rats dilatation turned to constriction after beta-adrenoreceptor blocking drugs. The vessels affected by dilatation could not be determined. Thus CO2 can enhance or diminish the action of hypoxia but the circumstances determining one or other action are not resolved."}
{"id": "PMID:23192", "title": "Inhibitory effects of clonidine on responses to sympathetic nerve stimulation in the pithed rat.", "content": "1. The spinal sympathetic outflow to the eyelid, heart, splanchnic blood vessels, vas deferens and anococcygeus muscle was stimulated in pithed rats. 2. Clonidine inhibited sympathetic outflow to all of the tissues studied. The inhibitory effects of clonidine on cardiac nerves and hypogastric nerves were antagonized by phentolamine. 3. Clonidine produced a postsynaptic alpha-adrenoceptor agonist action on the eyelid, splanchnic blood vessels and the anococcygeus muscle. These effects were also antagonized by phentolamine. 4. The effects of clonidine, naphazoline and oxymetazoline on pre- and postsynaptic alpha-adrenoceptors were determined. 5. The presynaptic alpha-adrenoceptors employed were situated in either the sympathetic cardiac or hypogastric nerve terminals. Increases in diastolic blood pressure were used to assess concurrent postsynaptic alpha-adrenoceptor agonist activity. 6. The presynaptic alpha-adrenoceptor agonist potencies of clonidine, naphazoline and oxymetazoline were very similar on cardiac nerve terminals whereas on the hypogastric nerve terminals oxymetazoline was about 6 times more potent than either naphazoline or clonidine. 7. The results support the view that presynaptic alpha-adrenoceptors regulate transmitter release in sympathetic nerves. There appear to be subtle differences between the presynaptic alpha-adrenoceptors of different sympathetic nerve endings.", "contents": "Inhibitory effects of clonidine on responses to sympathetic nerve stimulation in the pithed rat. 1. The spinal sympathetic outflow to the eyelid, heart, splanchnic blood vessels, vas deferens and anococcygeus muscle was stimulated in pithed rats. 2. Clonidine inhibited sympathetic outflow to all of the tissues studied. The inhibitory effects of clonidine on cardiac nerves and hypogastric nerves were antagonized by phentolamine. 3. Clonidine produced a postsynaptic alpha-adrenoceptor agonist action on the eyelid, splanchnic blood vessels and the anococcygeus muscle. These effects were also antagonized by phentolamine. 4. The effects of clonidine, naphazoline and oxymetazoline on pre- and postsynaptic alpha-adrenoceptors were determined. 5. The presynaptic alpha-adrenoceptors employed were situated in either the sympathetic cardiac or hypogastric nerve terminals. Increases in diastolic blood pressure were used to assess concurrent postsynaptic alpha-adrenoceptor agonist activity. 6. The presynaptic alpha-adrenoceptor agonist potencies of clonidine, naphazoline and oxymetazoline were very similar on cardiac nerve terminals whereas on the hypogastric nerve terminals oxymetazoline was about 6 times more potent than either naphazoline or clonidine. 7. The results support the view that presynaptic alpha-adrenoceptors regulate transmitter release in sympathetic nerves. There appear to be subtle differences between the presynaptic alpha-adrenoceptors of different sympathetic nerve endings."}
{"id": "PMID:23193", "title": "Evidence for the role of adrenocortical hormones in the regulation of noradrenaline and dopamine metabolism in certain brain areas.", "content": "1 Bilateral adrenalectomy suppressed body growth and increased the activity of tyrosine hydroxylase in rat striatum in a time-dependent manner. Fifteen days after adrenalectomy, the concentrations of noradrenaline were decreased significantly in hypothalamus and striatum, as were those of dopamine in brain stem and striatum. 2 Catechol-O-methyltransferase failed to change in response to adrenalectomy, but the activity of monoamine oxidase in cortex was significantly increased 7 days after surgery. These changes in various neurochemical parameters were even more pronounced 15 days after adrenal ablation. 3 Administration of corticosterone (10 mg/kg i.p.) to adrenalectomized rats effectively reversed the observed effects on brain amine metabolism. Corticosterone treatment for 7 days beginning from the 8th day of adrenalectomy virtually restored the concentrations of noradrenaline and dopamine as well as the activities of striatal tyrosine hydroxylase and cerebrocortical monoamine oxidase to the values seen for sham-operated controls. 4 Our data suggest that changes seen in brain noradrenaline and dopamine of adrenalectomized rats are specific to adrenocortical steroids and that these hormones play a role in the regulation of catecholamine formation.", "contents": "Evidence for the role of adrenocortical hormones in the regulation of noradrenaline and dopamine metabolism in certain brain areas. 1 Bilateral adrenalectomy suppressed body growth and increased the activity of tyrosine hydroxylase in rat striatum in a time-dependent manner. Fifteen days after adrenalectomy, the concentrations of noradrenaline were decreased significantly in hypothalamus and striatum, as were those of dopamine in brain stem and striatum. 2 Catechol-O-methyltransferase failed to change in response to adrenalectomy, but the activity of monoamine oxidase in cortex was significantly increased 7 days after surgery. These changes in various neurochemical parameters were even more pronounced 15 days after adrenal ablation. 3 Administration of corticosterone (10 mg/kg i.p.) to adrenalectomized rats effectively reversed the observed effects on brain amine metabolism. Corticosterone treatment for 7 days beginning from the 8th day of adrenalectomy virtually restored the concentrations of noradrenaline and dopamine as well as the activities of striatal tyrosine hydroxylase and cerebrocortical monoamine oxidase to the values seen for sham-operated controls. 4 Our data suggest that changes seen in brain noradrenaline and dopamine of adrenalectomized rats are specific to adrenocortical steroids and that these hormones play a role in the regulation of catecholamine formation."}
{"id": "PMID:23194", "title": "alpha-Adrenoceptors in the mouse vas deferens and their effects on its response to electrical stimulation.", "content": "1 Noradrenaline (ID50, 0.75 micrometer) and clonidine (ID50, 2.8 nM) produced a dose-related inhibition of the twitch response of the isolated vas deferens of the mouse to electrical stimulation, their effectiveness decreasing as frequency of stimulation increased from 0.2 to 16 hertz. 2 Phenylephrine (1.0--2.0 micrometer) produced a dose-related contraction of the mouse isolated vas deferens and potentiated the responses to field stimulation. 3 Yohimbine (10 nM) antagonized the inhibitory effects of noradrenaline and clonidine, but had no effect on the motor activity of phenylephrine. At a concentration of 128 nM yohimbine potentiated the twitch response by 110% at 1 Hz, but its effectiveness decreased with increasing frequency of stimulation up to 16 hertz. 4 Thymoxamine (0.3 micrometer) antagonized the effects of phenylephrine, but not those of clonidine. 5 From a consideration of the known characteristics of pre- and postsynaptic alpha-adrenoceptors, it is concluded that the inhibitory effect of noradrenaline is produced by stimulation of the former and the effects of phenylephrine by stimulation of the latter.", "contents": "alpha-Adrenoceptors in the mouse vas deferens and their effects on its response to electrical stimulation. 1 Noradrenaline (ID50, 0.75 micrometer) and clonidine (ID50, 2.8 nM) produced a dose-related inhibition of the twitch response of the isolated vas deferens of the mouse to electrical stimulation, their effectiveness decreasing as frequency of stimulation increased from 0.2 to 16 hertz. 2 Phenylephrine (1.0--2.0 micrometer) produced a dose-related contraction of the mouse isolated vas deferens and potentiated the responses to field stimulation. 3 Yohimbine (10 nM) antagonized the inhibitory effects of noradrenaline and clonidine, but had no effect on the motor activity of phenylephrine. At a concentration of 128 nM yohimbine potentiated the twitch response by 110% at 1 Hz, but its effectiveness decreased with increasing frequency of stimulation up to 16 hertz. 4 Thymoxamine (0.3 micrometer) antagonized the effects of phenylephrine, but not those of clonidine. 5 From a consideration of the known characteristics of pre- and postsynaptic alpha-adrenoceptors, it is concluded that the inhibitory effect of noradrenaline is produced by stimulation of the former and the effects of phenylephrine by stimulation of the latter."}
{"id": "PMID:23195", "title": "The role of social anxiety in social interaction difficulties.", "content": "Social anxiety was found to be the most common complaint in a sample of psychiatric patients reporting social interaction difficulties. High social anxiety was shown to be associated with impairments to social behaviour in socially anxious psychiatric patients and non-psychiatric volunteers. A comparison was made of systematic desensitization and a form of social skills training in the treatment of social interaction difficulties associated with high social anxiety. This indicated that while both therapies were effective in the reduction of social anxiety, the training programme was the more effective in reducing problem behaviour, but desensitization appeared to lead to a wider generalization of improvement as indicated by increases in social participation.", "contents": "The role of social anxiety in social interaction difficulties. Social anxiety was found to be the most common complaint in a sample of psychiatric patients reporting social interaction difficulties. High social anxiety was shown to be associated with impairments to social behaviour in socially anxious psychiatric patients and non-psychiatric volunteers. A comparison was made of systematic desensitization and a form of social skills training in the treatment of social interaction difficulties associated with high social anxiety. This indicated that while both therapies were effective in the reduction of social anxiety, the training programme was the more effective in reducing problem behaviour, but desensitization appeared to lead to a wider generalization of improvement as indicated by increases in social participation."}
{"id": "PMID:23196", "title": "The effect of temperature on the motility and viability of sperm.", "content": "In specimens of semen kept at 37 degrees C sperm lose their motility and viability. If kept at 4 degrees C they retain their viability but lose their motility from so-called thermal shock. The best temperature to keep semen in order to preserve sperm motility is 20 degrees C. Loss of motility at 37 degrees C is not entirely prevented by prevention of bacterial contamination with antibiotics.", "contents": "The effect of temperature on the motility and viability of sperm. In specimens of semen kept at 37 degrees C sperm lose their motility and viability. If kept at 4 degrees C they retain their viability but lose their motility from so-called thermal shock. The best temperature to keep semen in order to preserve sperm motility is 20 degrees C. Loss of motility at 37 degrees C is not entirely prevented by prevention of bacterial contamination with antibiotics."}
{"id": "PMID:23197", "title": "Antinuclear antibodies in patients receiving non-practolol beta-blockers.", "content": "Antinuclear antibodies (ANA) were found in 54 (7.0%) out of 767 treated hypertensive patients compared with 59 (2.4%) out of 2470 healthy controls. Inclusion of a non-practolol beta-blocker in the treatment regimen did not significantly affect the incidence of ANA. ANA was found in significantly more patients being treated with methyldopa (13.0%) than patients receiving other hypotensive agents (3.8%). Non-practolol beta-blockers in combination with methyldopa did not increase the incidence of ANA further.", "contents": "Antinuclear antibodies in patients receiving non-practolol beta-blockers. Antinuclear antibodies (ANA) were found in 54 (7.0%) out of 767 treated hypertensive patients compared with 59 (2.4%) out of 2470 healthy controls. Inclusion of a non-practolol beta-blocker in the treatment regimen did not significantly affect the incidence of ANA. ANA was found in significantly more patients being treated with methyldopa (13.0%) than patients receiving other hypotensive agents (3.8%). Non-practolol beta-blockers in combination with methyldopa did not increase the incidence of ANA further."}
{"id": "PMID:23207", "title": "On the use of some phenothiazine derivatives in chickens.", "content": "1. Perphenazine, promethazine and levomepromazine induced sedation in young pullets following intramuscular injections. 2. The best results were obtained with perphenazine at a dose rate of 1-5 mg/kg.", "contents": "On the use of some phenothiazine derivatives in chickens. 1. Perphenazine, promethazine and levomepromazine induced sedation in young pullets following intramuscular injections. 2. The best results were obtained with perphenazine at a dose rate of 1-5 mg/kg."}
{"id": "PMID:23209", "title": "Further studies on the cardiolipin phosphodiesterase of Escherichia coli.", "content": "The cardiolipin phosphodiesterase of Escherichia coli was further characterized. This enzyme has a pH optimum of 7.0 and is Mg2+ dependent. Mn2+ and Co2+ could replace Mg2+ but other divalent cations were inhibitory or without effect. The enzyme is not periplasmic and does not appear to be associated with membrane fractions prepared by different methods. It is recovered as a soluble protein in the cytosol fraction but could not be readily purified because of its instability. With cell-free systems, a requirement for ATP or ADP could be shown under certain defined conditions. Other nucleotides were less effective or ineffective in stimulating the phosphodiesterase. The cells displayed the highest activity during the middle to late exponential stage but no marked requirement for ATP was apparent when the phosphodiesterase was obtained from such freshly grown cells. If, however, cells were starved for several hours in saline medium, the cardiolipin phosphodiesterase level fell and a requirement for added ATP could be shown. The cardiolipin phosphodiesterase is an enzyme distinct from cardiolipin synthase. The assay conditions are quite different from each of these enzymes as are their subcellular distributions.", "contents": "Further studies on the cardiolipin phosphodiesterase of Escherichia coli. The cardiolipin phosphodiesterase of Escherichia coli was further characterized. This enzyme has a pH optimum of 7.0 and is Mg2+ dependent. Mn2+ and Co2+ could replace Mg2+ but other divalent cations were inhibitory or without effect. The enzyme is not periplasmic and does not appear to be associated with membrane fractions prepared by different methods. It is recovered as a soluble protein in the cytosol fraction but could not be readily purified because of its instability. With cell-free systems, a requirement for ATP or ADP could be shown under certain defined conditions. Other nucleotides were less effective or ineffective in stimulating the phosphodiesterase. The cells displayed the highest activity during the middle to late exponential stage but no marked requirement for ATP was apparent when the phosphodiesterase was obtained from such freshly grown cells. If, however, cells were starved for several hours in saline medium, the cardiolipin phosphodiesterase level fell and a requirement for added ATP could be shown. The cardiolipin phosphodiesterase is an enzyme distinct from cardiolipin synthase. The assay conditions are quite different from each of these enzymes as are their subcellular distributions."}
{"id": "PMID:23211", "title": "Effect of monoamine receptor agonists and antagonists on cyclic AMP accumulation in human cerebral cortex slices.", "content": "In human cerebral cortex slices noradrenaline, isoproterenol (a beta-adrenergic agonist), dopamine, apomorphine (a dopaminergic agonist), and serotonin stimulated cyclic AMP formation: noradrenaline greater than or equal to isoproterenol greater than dopamine = apomorphine = serotonin. Clonidine (and alpha-adrenergic agonist) was ineffective in stimulating cyclic AMP formation in temporal cortex slices. The stimulatory effect of noradrenaline and isoproterenol was blocked by propranolol (a beta-adrenergic blocker) but not by phentolamine (an alpha-adrenergic blocker). Pimozide (a selective dopaminergic antagonist) inhibited the increase of cyclic AMP formation induced by dopamine or apomorphine but not that induced by noradrenaline, isoproterenol, or serotonin. Neither propranolol or phentolamine had any effect on dopamine- or serotonin-stimulated cyclic AMP formation. Chlorpromazine blocked the increase of cyclic AMP formation induced by noradrenaline, dopamine or serotonin, while cyproheptadine, a putative central serotonergic antagonist, was ineffective. These observations suggest that there may be at least two monoamine-sensitive adenylate cyclases in human cerebral cortex which have the characteristics of a beta-adrenergic and a dopaminergic receptor, respectively, and also possibly a serotonergic receptor.", "contents": "Effect of monoamine receptor agonists and antagonists on cyclic AMP accumulation in human cerebral cortex slices. In human cerebral cortex slices noradrenaline, isoproterenol (a beta-adrenergic agonist), dopamine, apomorphine (a dopaminergic agonist), and serotonin stimulated cyclic AMP formation: noradrenaline greater than or equal to isoproterenol greater than dopamine = apomorphine = serotonin. Clonidine (and alpha-adrenergic agonist) was ineffective in stimulating cyclic AMP formation in temporal cortex slices. The stimulatory effect of noradrenaline and isoproterenol was blocked by propranolol (a beta-adrenergic blocker) but not by phentolamine (an alpha-adrenergic blocker). Pimozide (a selective dopaminergic antagonist) inhibited the increase of cyclic AMP formation induced by dopamine or apomorphine but not that induced by noradrenaline, isoproterenol, or serotonin. Neither propranolol or phentolamine had any effect on dopamine- or serotonin-stimulated cyclic AMP formation. Chlorpromazine blocked the increase of cyclic AMP formation induced by noradrenaline, dopamine or serotonin, while cyproheptadine, a putative central serotonergic antagonist, was ineffective. These observations suggest that there may be at least two monoamine-sensitive adenylate cyclases in human cerebral cortex which have the characteristics of a beta-adrenergic and a dopaminergic receptor, respectively, and also possibly a serotonergic receptor."}
{"id": "PMID:23212", "title": "The effects of changes in inspired oxygen concentration on the experimental production of pulmonary edema in the dog with chronic left ventricular overload.", "content": "A twofold increase in left ventricular output was achieved by suturing a Telfon graft between the aorta and left atrium in dogs. Three weeks after surgery the animals were anesthetized and found to have left ventricular end-diastolic pressures averaging 36 mmHg with markedly elevated right ventricular systolic pressures (RVSP). Oxygen breathing resulted in a decrease in left ventricular pressures, RVSP, and arterial pressure in those animals which survived hypoxia. Fifty percent of the shunted dogs subsequently developed fatal pulmonary edema when allowed to breathe 10% oxygen in nitrogen. These animals showed no change in left ventricular function or pulmonary artery pressure (RVSP) in response to pure oxygen administration. It is suggested that there is a gradation of hemodynamic response to pure oxygen depending on the severity of left ventricular overload. In the severest case the 'fixing' of pulmonary hypertension may be due to neurohumoral mechanisms. The subsequent development of pulmonary edema in these animals with hypoxia either involves a change in permeability or a redistribution of hydrostatic pressure within the pulmonary vasculature.", "contents": "The effects of changes in inspired oxygen concentration on the experimental production of pulmonary edema in the dog with chronic left ventricular overload. A twofold increase in left ventricular output was achieved by suturing a Telfon graft between the aorta and left atrium in dogs. Three weeks after surgery the animals were anesthetized and found to have left ventricular end-diastolic pressures averaging 36 mmHg with markedly elevated right ventricular systolic pressures (RVSP). Oxygen breathing resulted in a decrease in left ventricular pressures, RVSP, and arterial pressure in those animals which survived hypoxia. Fifty percent of the shunted dogs subsequently developed fatal pulmonary edema when allowed to breathe 10% oxygen in nitrogen. These animals showed no change in left ventricular function or pulmonary artery pressure (RVSP) in response to pure oxygen administration. It is suggested that there is a gradation of hemodynamic response to pure oxygen depending on the severity of left ventricular overload. In the severest case the 'fixing' of pulmonary hypertension may be due to neurohumoral mechanisms. The subsequent development of pulmonary edema in these animals with hypoxia either involves a change in permeability or a redistribution of hydrostatic pressure within the pulmonary vasculature."}
{"id": "PMID:23213", "title": "Symposium on intensive care: 3. Upper gastrointestinal bleeding in the intensive care unit.", "content": "Bleeding from hemorrhagic erosions in the stomach or duodenum of seriously ill patients is associated with a high mortality. While the pathogenesis of such lesions is by no means certain, it is known that they are universal after shock, sepsis or severe burns. Fiberoptic endoscopy has become the most valuable means of diagnosis. This should be preceded by gastric irrigaiton, which usually sufficies to control bleeding caused by acetylsalicylic acid or alcohol, or both. Neutralization of gastric acidity is essential. The histamine HI-receptor antagonist, cimetidine, was used in 27 patients with erosive gastritis, and bleeding ceased in 24. There is a prospect that sugh agents will obviate the necessity of total gastrectomy in the occasional resistant cases in favour of conservative surgery.", "contents": "Symposium on intensive care: 3. Upper gastrointestinal bleeding in the intensive care unit. Bleeding from hemorrhagic erosions in the stomach or duodenum of seriously ill patients is associated with a high mortality. While the pathogenesis of such lesions is by no means certain, it is known that they are universal after shock, sepsis or severe burns. Fiberoptic endoscopy has become the most valuable means of diagnosis. This should be preceded by gastric irrigaiton, which usually sufficies to control bleeding caused by acetylsalicylic acid or alcohol, or both. Neutralization of gastric acidity is essential. The histamine HI-receptor antagonist, cimetidine, was used in 27 patients with erosive gastritis, and bleeding ceased in 24. There is a prospect that sugh agents will obviate the necessity of total gastrectomy in the occasional resistant cases in favour of conservative surgery."}
{"id": "PMID:23218", "title": "A monolayer (pi,deltaV) study of the ionic properties of alanylphosphatidylglycerol: effects of pH and ions.", "content": "1,2-Didodecanolyl-sn-glycero-3-phosphoryl-1'-(3'-O-L-alanyl)-sn-glycerol (Ala-PG) has been synthetized. Its ionic properties have been studied at the air-water interface through film compressions and surface potential measurements as a function of subphase pH and ionic content (NaCl, Na2MoO4, CaCl2). The existence of the polar head in a loop conformation allowing for interactions between phosphate and amino groups is suggested. Ionic properties of Ala--PG clearly depended on subphase ionic strength but no specific interactions between either cations or anions in the subphase and phosphate or amino groups in the film could be detected. Results are interpreted in terms of ion-pair interactions at the interface between these two groups and anions and cations from the subphase. Occurrence of charge separation between these two groups, induced by increasing subphase ionic strength, is postulated. Since the molecular packing appeared independent of the subphase ionic content over a large domain of pH (3--7) and surface pressure (pi greater than 5 dyne/cm) and since the lipid can be considered as zwitterionic or slightly positive below pH 5--6, it is suggested that in the parent bacteria, grown under acidic conditions, Ala--PG could play a role in maintaining the membrane integrity and in preventing the passive diffusion of protons.", "contents": "A monolayer (pi,deltaV) study of the ionic properties of alanylphosphatidylglycerol: effects of pH and ions. 1,2-Didodecanolyl-sn-glycero-3-phosphoryl-1'-(3'-O-L-alanyl)-sn-glycerol (Ala-PG) has been synthetized. Its ionic properties have been studied at the air-water interface through film compressions and surface potential measurements as a function of subphase pH and ionic content (NaCl, Na2MoO4, CaCl2). The existence of the polar head in a loop conformation allowing for interactions between phosphate and amino groups is suggested. Ionic properties of Ala--PG clearly depended on subphase ionic strength but no specific interactions between either cations or anions in the subphase and phosphate or amino groups in the film could be detected. Results are interpreted in terms of ion-pair interactions at the interface between these two groups and anions and cations from the subphase. Occurrence of charge separation between these two groups, induced by increasing subphase ionic strength, is postulated. Since the molecular packing appeared independent of the subphase ionic content over a large domain of pH (3--7) and surface pressure (pi greater than 5 dyne/cm) and since the lipid can be considered as zwitterionic or slightly positive below pH 5--6, it is suggested that in the parent bacteria, grown under acidic conditions, Ala--PG could play a role in maintaining the membrane integrity and in preventing the passive diffusion of protons."}
{"id": "PMID:23221", "title": "[Purification of the glutamate decarboxylase from human brain].", "content": "A method of purifying the glutamate decarboxylase from human brain is described. The enzyme was purified 8 000 fold in regard to the initial homogenate and appears homogenous by electrophoresis, both in denaturing and non-denaturing conditions. The molecular weight of the native enzyme and its subunits indicate that GAD from human brain is formed by two similar if non identical polypeptide chains. The Km for glutamate and pyridoxal phosphate found for the human enzyme, respectively 1,2.10(-3) M and 0,13.10(-6) M, are close to the Km found for the Mouse enzyme.", "contents": "[Purification of the glutamate decarboxylase from human brain]. A method of purifying the glutamate decarboxylase from human brain is described. The enzyme was purified 8 000 fold in regard to the initial homogenate and appears homogenous by electrophoresis, both in denaturing and non-denaturing conditions. The molecular weight of the native enzyme and its subunits indicate that GAD from human brain is formed by two similar if non identical polypeptide chains. The Km for glutamate and pyridoxal phosphate found for the human enzyme, respectively 1,2.10(-3) M and 0,13.10(-6) M, are close to the Km found for the Mouse enzyme."}
{"id": "PMID:23223", "title": "Endotoxemia and large intestinal blood flow in subhuman primates.", "content": "The hemodynamic effects of Escherichia coli endotoxin (LD80) were measured in the large intestine of anesthetized Rhesus monkeys to determine whether this organ contributes to the pathogenesis of experimental shock. Inferior mesenteric arterial blood flow (IMF) was measured with an electromagnetic flowmeter. Pressures within the aorta (AP) and portal vein (PP) were recorded. Distribution of colon blood flow was measured with radioactive microspheres: Ce, Sr, and Cr were injected into the left heart. Reference blood samples were obtained from a femoral artery. Mean control IMF was 22.9 +/- 2.2 (SE) ml/min. Aortic pressure was 113 +/- 11 mm Hg, and PP was 6 +/- 1 mm Hg. Arterial blood pH was 7.43 +/- 0.02; pO2 and pCO2 were 93.4 and 37.1 mm Hg, respectively. All parameters were measured at hourly intervals for 4 hr. Neither IMF nor its distribution within the colon changed during the entire observation period. Aortic pressure fell to a low of 60 +/- 6 mm Hg (p less than 0.02) at 3 hr; PP, pO2 and pCO2 were unchanged by endotoxin. Arterial blood pH fell to 7.315 +/- 0.020 at 4 hr (p less than 0.01). These observations indicate that the colon is not a \"target organ\" of endotoxic shock in subhuman primates, despite considerable hypotension and metabolic disturbances subsequent to near lethal endotoxemia.", "contents": "Endotoxemia and large intestinal blood flow in subhuman primates. The hemodynamic effects of Escherichia coli endotoxin (LD80) were measured in the large intestine of anesthetized Rhesus monkeys to determine whether this organ contributes to the pathogenesis of experimental shock. Inferior mesenteric arterial blood flow (IMF) was measured with an electromagnetic flowmeter. Pressures within the aorta (AP) and portal vein (PP) were recorded. Distribution of colon blood flow was measured with radioactive microspheres: Ce, Sr, and Cr were injected into the left heart. Reference blood samples were obtained from a femoral artery. Mean control IMF was 22.9 +/- 2.2 (SE) ml/min. Aortic pressure was 113 +/- 11 mm Hg, and PP was 6 +/- 1 mm Hg. Arterial blood pH was 7.43 +/- 0.02; pO2 and pCO2 were 93.4 and 37.1 mm Hg, respectively. All parameters were measured at hourly intervals for 4 hr. Neither IMF nor its distribution within the colon changed during the entire observation period. Aortic pressure fell to a low of 60 +/- 6 mm Hg (p less than 0.02) at 3 hr; PP, pO2 and pCO2 were unchanged by endotoxin. Arterial blood pH fell to 7.315 +/- 0.020 at 4 hr (p less than 0.01). These observations indicate that the colon is not a \"target organ\" of endotoxic shock in subhuman primates, despite considerable hypotension and metabolic disturbances subsequent to near lethal endotoxemia."}
{"id": "PMID:23219", "title": "[Technical note on the isolation of arboviruses by inoculation in young mice: preparation of the mosquito brei].", "content": "Studying the effects of centrifugation and deep freezing on the quantity of yellow fever virus in a grinded pool of mosquitoes, the authors followed the mortality rate of inoculated baby mice with twenty five artificially infected mosquitoes treated in four different ways. The statistical analysis of the results show that centrifugation and deep freezing have both an effect on the titer of virus and that the addition of the two treatments have an effect superior to the addition of the separate effects of each of them. The authors propose a new technic for the preparation of pools of mosquitoes, without centrifugation or deep freezing.", "contents": "[Technical note on the isolation of arboviruses by inoculation in young mice: preparation of the mosquito brei]. Studying the effects of centrifugation and deep freezing on the quantity of yellow fever virus in a grinded pool of mosquitoes, the authors followed the mortality rate of inoculated baby mice with twenty five artificially infected mosquitoes treated in four different ways. The statistical analysis of the results show that centrifugation and deep freezing have both an effect on the titer of virus and that the addition of the two treatments have an effect superior to the addition of the separate effects of each of them. The authors propose a new technic for the preparation of pools of mosquitoes, without centrifugation or deep freezing."}
{"id": "PMID:23225", "title": "Simple, refined fluorometric method for measuring cystyl-amino peptidase activity.", "content": "Cystyl-amino peptidase (EC 3.4.11.3) activity in serum or plasma was measured fluorometrically using L-cystine-di-beta-naphthylamide in the absence and presence of thiol such as mercaptoethanol. In the presence of thiol, L-cystine-di-beta-naphthylamide is converted to L-cysteine-beta-naphthylamide, and the enzyme activity to hydrolyze L-cysteine-beta-naphthylamide can be measured, while in the absence of thiol, the enzyme activity to hydrolyze L-cystine-di-beta-naphthylamide is determined. Thiol added did not affect various aminopeptidase activities. The present method is able to measure the enzyme activity hydrolyzing L-cystine-di-beta-naphthylamide and L-cysteine-beta-naphthylamide simultaneously and separately using only L-cysteine-di-beta-naphthylamide. This method is simple, sensitive and useful in clinical routine work, assessing placental function for the evaluation of the pregnant status.", "contents": "Simple, refined fluorometric method for measuring cystyl-amino peptidase activity. Cystyl-amino peptidase (EC 3.4.11.3) activity in serum or plasma was measured fluorometrically using L-cystine-di-beta-naphthylamide in the absence and presence of thiol such as mercaptoethanol. In the presence of thiol, L-cystine-di-beta-naphthylamide is converted to L-cysteine-beta-naphthylamide, and the enzyme activity to hydrolyze L-cysteine-beta-naphthylamide can be measured, while in the absence of thiol, the enzyme activity to hydrolyze L-cystine-di-beta-naphthylamide is determined. Thiol added did not affect various aminopeptidase activities. The present method is able to measure the enzyme activity hydrolyzing L-cystine-di-beta-naphthylamide and L-cysteine-beta-naphthylamide simultaneously and separately using only L-cysteine-di-beta-naphthylamide. This method is simple, sensitive and useful in clinical routine work, assessing placental function for the evaluation of the pregnant status."}
{"id": "PMID:23226", "title": "Influence of thiocyanate ions on starch-iodine reaction used for the estimation of alpha-amylase activity.", "content": "A strong simulating effect of thiocyanate ions during the estimation of alpha-amylase by the amyloclastic method is shown. Thiocyanate ions themselves catalyse the decolorization of the starch-iodine complex. This may lead to wrong values during determination of alpha-amylase by this method. The rate of thiocyanate-iodine reaction depends upon the hydrogen ion concentration of the iodine reagent.", "contents": "Influence of thiocyanate ions on starch-iodine reaction used for the estimation of alpha-amylase activity. A strong simulating effect of thiocyanate ions during the estimation of alpha-amylase by the amyloclastic method is shown. Thiocyanate ions themselves catalyse the decolorization of the starch-iodine complex. This may lead to wrong values during determination of alpha-amylase by this method. The rate of thiocyanate-iodine reaction depends upon the hydrogen ion concentration of the iodine reagent."}
{"id": "PMID:23227", "title": "A protein-binding assay for measurement of biotin in physiological fluids.", "content": "A sensitive and convenient protein-binding assay for biotin in physiological fluids is described. The method is based upon the binding of an iodinated biotin conjugate by avidin followed by separation of bound and free conjugate by charcoal absorption. Adult plasma biotin levels averaged 1.26 pmol/ml, a value comparable to that determined by microbiological assays for biotin.", "contents": "A protein-binding assay for measurement of biotin in physiological fluids. A sensitive and convenient protein-binding assay for biotin in physiological fluids is described. The method is based upon the binding of an iodinated biotin conjugate by avidin followed by separation of bound and free conjugate by charcoal absorption. Adult plasma biotin levels averaged 1.26 pmol/ml, a value comparable to that determined by microbiological assays for biotin."}
{"id": "PMID:23228", "title": "Calibration of a turbidimetric assay of serum lipase activity.", "content": "Serum lipase activity has been measured by the turbidimetric method of Shihabi and Bishop, using an olive oil suspension as substrate (Shihabi, Z.K. and Bishop, C. (1971) Clin. Chem. 17, 1150-1153). For this method we developed a new calibration procedure, which can be carried out with great precision. Moreover, the technique is simple and fast and therefore suitable for routine use in clinical chemical laboratories. The new calibration procedure consists of the continuous titration of fatty acids, liberated by lipase from the sample, under the same reaction conditions as those used in the turbidimetric assay. A close correlation has been found with the results from the method of Shihabi and Bishop, in which method calibration has been carried out by making use of the linear relationship between the olive oil concentration and the absorbance of the suspension. In our method, the numerical results are twice those obtained by the method of Shihabi and Bishop. A possible explanation for this phenomenon is given.", "contents": "Calibration of a turbidimetric assay of serum lipase activity. Serum lipase activity has been measured by the turbidimetric method of Shihabi and Bishop, using an olive oil suspension as substrate (Shihabi, Z.K. and Bishop, C. (1971) Clin. Chem. 17, 1150-1153). For this method we developed a new calibration procedure, which can be carried out with great precision. Moreover, the technique is simple and fast and therefore suitable for routine use in clinical chemical laboratories. The new calibration procedure consists of the continuous titration of fatty acids, liberated by lipase from the sample, under the same reaction conditions as those used in the turbidimetric assay. A close correlation has been found with the results from the method of Shihabi and Bishop, in which method calibration has been carried out by making use of the linear relationship between the olive oil concentration and the absorbance of the suspension. In our method, the numerical results are twice those obtained by the method of Shihabi and Bishop. A possible explanation for this phenomenon is given."}
{"id": "PMID:23229", "title": "The effect of sickle cell haemoglobin polymerization on hydrogen ion dissociation.", "content": "An increase in hydrogen ion dissociation was found on sickling due to sickle cell haemoglobin polymerization. Since a decrease in pH favours sickling, this might enhance the sickling process in a vicious cycle.", "contents": "The effect of sickle cell haemoglobin polymerization on hydrogen ion dissociation. An increase in hydrogen ion dissociation was found on sickling due to sickle cell haemoglobin polymerization. Since a decrease in pH favours sickling, this might enhance the sickling process in a vicious cycle."}
{"id": "PMID:23230", "title": "The mechanism underlying increased tryptaminuria after alcohol ingestion.", "content": "It is demonstrated that the increased tryptaminuria which follows alcohol ingestion can be abolished by the concurrent ingestion of alkali even when the amount of alkali consumed is insufficient to increase urinary pH to 6.5 (above which pH a fall in urinary tryptamine may be anticipated, from previous studies, to occur). It is suggested that this increased tryptaminuria is largely if not wholly dependent on the metabolic acidosis induced by alcohol which the concurrent ingestion of alkali abolishes.", "contents": "The mechanism underlying increased tryptaminuria after alcohol ingestion. It is demonstrated that the increased tryptaminuria which follows alcohol ingestion can be abolished by the concurrent ingestion of alkali even when the amount of alkali consumed is insufficient to increase urinary pH to 6.5 (above which pH a fall in urinary tryptamine may be anticipated, from previous studies, to occur). It is suggested that this increased tryptaminuria is largely if not wholly dependent on the metabolic acidosis induced by alcohol which the concurrent ingestion of alkali abolishes."}
{"id": "PMID:23231", "title": "A benign deficiency of typeB beta-galactosidase in human liver.", "content": "The type A or 'acid' and type B or 'neutral' beta-galactosidase activities have been measured in post-mortem liver samples from individuals dying of non-genetic diseases and patients dying of ganglioside storage disease other than GM1 gangliosidosis. The type A activities fell within the established normal range in all samples. The type B activities showed a biomodal distribution suggesting the occurrence of two distinct populations of human individuals. The greater proportion had activities within the range 11.67 pkat/mg of protein (+/- 3.33, S.D.), while others had lower activities in the range 0.48 pkat/mg of protein (+/- 0.38, S.D.). No clinical symptoms were associated with the much lower type B beta-galactosidase activities and it appears that this beta-galactosidase deficiency could be found in the original tissues. Methods of screening for type B beta-galactosidase deficiency are described and the significance of this enzyme deficiency is discussed.", "contents": "A benign deficiency of typeB beta-galactosidase in human liver. The type A or 'acid' and type B or 'neutral' beta-galactosidase activities have been measured in post-mortem liver samples from individuals dying of non-genetic diseases and patients dying of ganglioside storage disease other than GM1 gangliosidosis. The type A activities fell within the established normal range in all samples. The type B activities showed a biomodal distribution suggesting the occurrence of two distinct populations of human individuals. The greater proportion had activities within the range 11.67 pkat/mg of protein (+/- 3.33, S.D.), while others had lower activities in the range 0.48 pkat/mg of protein (+/- 0.38, S.D.). No clinical symptoms were associated with the much lower type B beta-galactosidase activities and it appears that this beta-galactosidase deficiency could be found in the original tissues. Methods of screening for type B beta-galactosidase deficiency are described and the significance of this enzyme deficiency is discussed."}
{"id": "PMID:23232", "title": "Acquired enzymopathy of erythrocyte glucose-6-phosphate dehydrogenase in acute viral hepatitis.", "content": "Erythrocyte glucose-6-phosphate dehydrogenase from patients with acute viral hepatitis has been purified and characterized. The enzyme showed decreased activity (relative to protein), reduced affinity for glucose 6-phosphate and was inactivated at 45 degrees C or at low pH values. The activity and properties of normal erythrocyte enzyme, incubated in vitro with blood plasma of patients, showed a similar pattern of modifications. Incubation with bilirubin affected the enzyme stability, but not its activity or affinity for substrate.", "contents": "Acquired enzymopathy of erythrocyte glucose-6-phosphate dehydrogenase in acute viral hepatitis. Erythrocyte glucose-6-phosphate dehydrogenase from patients with acute viral hepatitis has been purified and characterized. The enzyme showed decreased activity (relative to protein), reduced affinity for glucose 6-phosphate and was inactivated at 45 degrees C or at low pH values. The activity and properties of normal erythrocyte enzyme, incubated in vitro with blood plasma of patients, showed a similar pattern of modifications. Incubation with bilirubin affected the enzyme stability, but not its activity or affinity for substrate."}
{"id": "PMID:23233", "title": "Lysosomal glycosidase activities in human hair roots.", "content": "The levels of three lysosomal glycosidase, alpha-D-mannosidase, a-L-fucosidase and beta-D-hexosaminidase have been determined in normal hair roots and in hair roots obtained from a patient with mannosidosis. The most active glycosidase in normal hair roots was beta-D-hexosaminidase, followed by alpha-L-fucosidase and alpha-D-mannosidase. There was no alpha-D-mannosidase activity in the hair roots of the patient with mannosidosis. The significance of these results is discussed in relation to the detection of lysosomal storage diseases.", "contents": "Lysosomal glycosidase activities in human hair roots. The levels of three lysosomal glycosidase, alpha-D-mannosidase, a-L-fucosidase and beta-D-hexosaminidase have been determined in normal hair roots and in hair roots obtained from a patient with mannosidosis. The most active glycosidase in normal hair roots was beta-D-hexosaminidase, followed by alpha-L-fucosidase and alpha-D-mannosidase. There was no alpha-D-mannosidase activity in the hair roots of the patient with mannosidosis. The significance of these results is discussed in relation to the detection of lysosomal storage diseases."}
{"id": "PMID:23265", "title": "Peptidases in germinating barley grain: properties, localization and possible functions.", "content": "Barley grain contains about 10% insoluble reserve proteins. When the grain germinates the reserve proteins are hydrolysed to amino acids and transported to the growing tissues of the seedling. In the resting grain most of the reserve proteins are 'packed' into the non-living storage tissue, the starchy endosperm. During germination the internal pH of the starchy endosperm is about 5, and it contains high activities of proteinases (secreted by the living aleurone cells) and carboxypeptidases, all with pH optima between 4 and 6. As a whole the starchy endosperm of a germinating grain resembles a giant secondary lysosome. Adjacent to the starchy endosperm is a specialized absorptive and processing tissue, the scutellum. This organ contains very high activities of the 'acid carboxypeptidases' and also two 'alkaline peptidase': a leucine aminopeptidase and a dipeptidase, both pH optima at 8 to 10. The high peptidase activities in the scutellum suggest that the hydrolysis products of the reserve proteins are absorbed from the starchy endosperm as a mixture of amino acids and small peptides, which are hydrolysed to amino acids in the scutellum before transport to the growing seedling tissues.", "contents": "Peptidases in germinating barley grain: properties, localization and possible functions. Barley grain contains about 10% insoluble reserve proteins. When the grain germinates the reserve proteins are hydrolysed to amino acids and transported to the growing tissues of the seedling. In the resting grain most of the reserve proteins are 'packed' into the non-living storage tissue, the starchy endosperm. During germination the internal pH of the starchy endosperm is about 5, and it contains high activities of proteinases (secreted by the living aleurone cells) and carboxypeptidases, all with pH optima between 4 and 6. As a whole the starchy endosperm of a germinating grain resembles a giant secondary lysosome. Adjacent to the starchy endosperm is a specialized absorptive and processing tissue, the scutellum. This organ contains very high activities of the 'acid carboxypeptidases' and also two 'alkaline peptidase': a leucine aminopeptidase and a dipeptidase, both pH optima at 8 to 10. The high peptidase activities in the scutellum suggest that the hydrolysis products of the reserve proteins are absorbed from the starchy endosperm as a mixture of amino acids and small peptides, which are hydrolysed to amino acids in the scutellum before transport to the growing seedling tissues."}
{"id": "PMID:23267", "title": "Hepatic mono-oxygenase activity and hepatocellular morphology in chickens treated with 3-methylcholanthrene.", "content": "Hepatic drug metabolism in the chicken was investigated. White leghorn chickens were administered 20 mg of 3-methylcholanthrene (3MC) per kg 72 and 48 hr before killing. Levels of hepatic cytochrome P-450 were increased approximately 4-fold. In vitro ethylmorphine N-demethylase (ND) activity was enhanced approximately 1.7-fold, aniline hydroxylase (AH) was increased 2.5-fold, aryl hydrocarbon hydroxylase was increased 20-fold, and NADPH-cytochrome c reductase was unchanged. The Vmax was increased for both ND and AH activities, but the KM for demethylation was depressed whereas that for hydroxylation of aniline was increased. The metabolism of hexobarbital in vivo was not enhanced by 3MC treatment. In brief, the distinctive features of the hepatic mono-oxygenase system of the 3MC-treated chicken were: (a) enhanced ethylmorphine N-demethylase activity, (b) a shift in the Soret peak in the CO-difference spectrum of reduced cytochrome P-450 from the control value of 452 nm to 449 nm, and (c) proliferation and pronounced vesiculation of the hepatic endoplasmic reticulum as revealed by electron-microscopic examination.", "contents": "Hepatic mono-oxygenase activity and hepatocellular morphology in chickens treated with 3-methylcholanthrene. Hepatic drug metabolism in the chicken was investigated. White leghorn chickens were administered 20 mg of 3-methylcholanthrene (3MC) per kg 72 and 48 hr before killing. Levels of hepatic cytochrome P-450 were increased approximately 4-fold. In vitro ethylmorphine N-demethylase (ND) activity was enhanced approximately 1.7-fold, aniline hydroxylase (AH) was increased 2.5-fold, aryl hydrocarbon hydroxylase was increased 20-fold, and NADPH-cytochrome c reductase was unchanged. The Vmax was increased for both ND and AH activities, but the KM for demethylation was depressed whereas that for hydroxylation of aniline was increased. The metabolism of hexobarbital in vivo was not enhanced by 3MC treatment. In brief, the distinctive features of the hepatic mono-oxygenase system of the 3MC-treated chicken were: (a) enhanced ethylmorphine N-demethylase activity, (b) a shift in the Soret peak in the CO-difference spectrum of reduced cytochrome P-450 from the control value of 452 nm to 449 nm, and (c) proliferation and pronounced vesiculation of the hepatic endoplasmic reticulum as revealed by electron-microscopic examination."}
{"id": "PMID:23269", "title": "N-Acetylation of drugs. A genetically controlled reciprocal relationship between drug N-acetylating enzymes of rabbit liver and peripheral blood cells.", "content": "The reciprocal relation between liver isoniazid N-acetyltransferase and blood p-aminobenzoic and N-acetyltransferase previously reported is confirmed and found to be expressed in erythrocytes and lymphocytes of genetically rapid and slow isoniazid-acetylator rabbits. Both erythrocytes and lymphocytes from slow acetylator rabbits contained 2.5-3.3 times as much p-aminobenzoic acid N-acetyltransferase activity as the same cells from rapid acetylator rabbits. Mechanisms which might account for the reciprocal association between liver and blood N-acetyltransferases are considered.", "contents": "N-Acetylation of drugs. A genetically controlled reciprocal relationship between drug N-acetylating enzymes of rabbit liver and peripheral blood cells. The reciprocal relation between liver isoniazid N-acetyltransferase and blood p-aminobenzoic and N-acetyltransferase previously reported is confirmed and found to be expressed in erythrocytes and lymphocytes of genetically rapid and slow isoniazid-acetylator rabbits. Both erythrocytes and lymphocytes from slow acetylator rabbits contained 2.5-3.3 times as much p-aminobenzoic acid N-acetyltransferase activity as the same cells from rapid acetylator rabbits. Mechanisms which might account for the reciprocal association between liver and blood N-acetyltransferases are considered."}
{"id": "PMID:23272", "title": "Identification of the metabolites of trichlorocarbanilide in the rat.", "content": "The metabolism and excretion of 14C-labeled 3,4,4'-trichlorodiphenylurea has been studied in the rat after oral and iv administration. More than 80% of the administered radioactivity was excreted in the feces and urine over 5 days. Five isolated metabolites were characterized by mass spectrometry and by comparative thin-layer chromatography with synthesized compounds. Metabolites found include 2'-hydroxy-, 3'-hydroxy-, 6-hydroxy-, 2',6-dihydroxy- and 3',6-dihydroxy-3,4,4'-trichlorodiphenylurea.", "contents": "Identification of the metabolites of trichlorocarbanilide in the rat. The metabolism and excretion of 14C-labeled 3,4,4'-trichlorodiphenylurea has been studied in the rat after oral and iv administration. More than 80% of the administered radioactivity was excreted in the feces and urine over 5 days. Five isolated metabolites were characterized by mass spectrometry and by comparative thin-layer chromatography with synthesized compounds. Metabolites found include 2'-hydroxy-, 3'-hydroxy-, 6-hydroxy-, 2',6-dihydroxy- and 3',6-dihydroxy-3,4,4'-trichlorodiphenylurea."}
{"id": "PMID:23274", "title": "Absorption, metabolism, and excretion of 14C-tosifen in the dog and rat.", "content": "14C-tosifen [N-2-(1-phenylpropyl)-N'-p-tolyl sulfonylurea] was readily absorbed in both rats and dogs. The rates of absorption, metabolism, and urinary excretion were higher in the rat than in the dog. More of the drug was excreted via the feces than in the urine of the rat, whereas in the dog, the drug was primarily excreted into the urine. The parent drug was the major radioactive component in the plasma of both species. In the urine, however, only a negligible amount of tosifen was found. The major urinary metabolite was a hydroxymethyl derivative which accounted for about 60% and 40% of the total radioactivity in the urine of the dog and rat, respectively.", "contents": "Absorption, metabolism, and excretion of 14C-tosifen in the dog and rat. 14C-tosifen [N-2-(1-phenylpropyl)-N'-p-tolyl sulfonylurea] was readily absorbed in both rats and dogs. The rates of absorption, metabolism, and urinary excretion were higher in the rat than in the dog. More of the drug was excreted via the feces than in the urine of the rat, whereas in the dog, the drug was primarily excreted into the urine. The parent drug was the major radioactive component in the plasma of both species. In the urine, however, only a negligible amount of tosifen was found. The major urinary metabolite was a hydroxymethyl derivative which accounted for about 60% and 40% of the total radioactivity in the urine of the dog and rat, respectively."}
{"id": "PMID:23271", "title": "The metabolism of alpha-aminobenzo(b)thiophene-3-propionic acid (the sulfur analog of tryptophan) in the rat.", "content": "The biotransformation of 3H-labeled alpha-aminobenzo[b]thiophene-3-propionic acid (the sulfur analog of tryptophan) was investigated in rats. Forty-eight hours after ip administration, 80% of the radioactive dose was recovered in the urine and 5% in the feces; tissue levels of radioactivity accounted for the remainder of the administered dose. The urinary metabolites were identified by a combination of thin-layer chromatography, gas chromatography, and gas chromatography-mass spectrometry, and were quantitated by thin-layer chromatography and liquid-scintillation counting to give, as percentages of the administered dose, unchanged alpha-aminobenzo[b]thiophene-3-propionic acid (20.6%), benzo[b]thiophene-3-acetic acid (1.3%), benzo[b]thiophene-3-pyruvic acid (14.2%), benzo[b]thiophene-3-lactic acid (4.9%), and N-(benzo[b]thiophene-3-acetyl)glycine (46.2%).", "contents": "The metabolism of alpha-aminobenzo(b)thiophene-3-propionic acid (the sulfur analog of tryptophan) in the rat. The biotransformation of 3H-labeled alpha-aminobenzo[b]thiophene-3-propionic acid (the sulfur analog of tryptophan) was investigated in rats. Forty-eight hours after ip administration, 80% of the radioactive dose was recovered in the urine and 5% in the feces; tissue levels of radioactivity accounted for the remainder of the administered dose. The urinary metabolites were identified by a combination of thin-layer chromatography, gas chromatography, and gas chromatography-mass spectrometry, and were quantitated by thin-layer chromatography and liquid-scintillation counting to give, as percentages of the administered dose, unchanged alpha-aminobenzo[b]thiophene-3-propionic acid (20.6%), benzo[b]thiophene-3-acetic acid (1.3%), benzo[b]thiophene-3-pyruvic acid (14.2%), benzo[b]thiophene-3-lactic acid (4.9%), and N-(benzo[b]thiophene-3-acetyl)glycine (46.2%)."}
{"id": "PMID:23276", "title": "Excretion of phenytoin into semen of rabbits and man. Comparison with plasma levels.", "content": "The concentration of phenytoin (diphenylhydantoin, DPH) was measured in plasma and semen of rabbits and man. In the rabbit, a single iv injection of DPH (4.64 mg) resulted in a concentration-time curve for DPH in semen parallel to the concentration-time curve for DPH in plasma (t1/2beta = 171 +/- 29 min). A semen/plasma drug concentration ratio of 0.20 was maintained for at least 8 hr, demonstrating that DPH concentrations in semen are directly proportional to DPH concentrations in plasma. In epileptic subjects maintained on oral DPH the mean drug concentration in semen was 2.31 microgram/ml while that in plasma was 13.8 microgram/ml. The mean semen-plasma DPH concentration ratio in man was 0.17; this closely approximates the observed ratio in rabbits.", "contents": "Excretion of phenytoin into semen of rabbits and man. Comparison with plasma levels. The concentration of phenytoin (diphenylhydantoin, DPH) was measured in plasma and semen of rabbits and man. In the rabbit, a single iv injection of DPH (4.64 mg) resulted in a concentration-time curve for DPH in semen parallel to the concentration-time curve for DPH in plasma (t1/2beta = 171 +/- 29 min). A semen/plasma drug concentration ratio of 0.20 was maintained for at least 8 hr, demonstrating that DPH concentrations in semen are directly proportional to DPH concentrations in plasma. In epileptic subjects maintained on oral DPH the mean drug concentration in semen was 2.31 microgram/ml while that in plasma was 13.8 microgram/ml. The mean semen-plasma DPH concentration ratio in man was 0.17; this closely approximates the observed ratio in rabbits."}
{"id": "PMID:23278", "title": "Absorption and disposition of oxarbazole in man and laboratory animals.", "content": "Oxarbazole (9-benzoyl-1,2,3,4-tetrahydro-6-methoxycarbazole-3-carboxylic acid) was absorbed by human volunteers, rats, dogs, guinea pigs, and monkeys. In all species of laboratory animals studied, the major urinary metabolite was the product of O-demethylation, 9-benzoyl-1,2,3,4-tetrahydro-6-hydroxycarbazole-3-carboxylic acid; this metabolite was conjugated in all species except the guinea pig. The dog and monkey excreted small quantities of a conjugate of 1,2,3,4-tetrahydro-6-methoxycarbazole-3-carboxylic acid in the urine. Enterohepatic circulation was demonstrated in bile duct-cannulated rats, in which almost 90% of the radioactivity of a dose of 14C-oxarbazole had been excreted into the bile within 24 hr. At the time of peak blood radioactivity, intact oxarbazole was the major constituent circulating in the bloodstream of rats and monkeys that had received 14C-oxarbazole orally. The clearance of either intact oxarbazole in man and guinea pig, or undifferentiated radioactivity in rat, dog, and monkey, did not follow the kinetics of a simple model.", "contents": "Absorption and disposition of oxarbazole in man and laboratory animals. Oxarbazole (9-benzoyl-1,2,3,4-tetrahydro-6-methoxycarbazole-3-carboxylic acid) was absorbed by human volunteers, rats, dogs, guinea pigs, and monkeys. In all species of laboratory animals studied, the major urinary metabolite was the product of O-demethylation, 9-benzoyl-1,2,3,4-tetrahydro-6-hydroxycarbazole-3-carboxylic acid; this metabolite was conjugated in all species except the guinea pig. The dog and monkey excreted small quantities of a conjugate of 1,2,3,4-tetrahydro-6-methoxycarbazole-3-carboxylic acid in the urine. Enterohepatic circulation was demonstrated in bile duct-cannulated rats, in which almost 90% of the radioactivity of a dose of 14C-oxarbazole had been excreted into the bile within 24 hr. At the time of peak blood radioactivity, intact oxarbazole was the major constituent circulating in the bloodstream of rats and monkeys that had received 14C-oxarbazole orally. The clearance of either intact oxarbazole in man and guinea pig, or undifferentiated radioactivity in rat, dog, and monkey, did not follow the kinetics of a simple model."}
{"id": "PMID:23281", "title": "Rat hepatic microsomal cytochrome(s) P-450 induced by polybrominated biphenyls.", "content": "Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents.", "contents": "Rat hepatic microsomal cytochrome(s) P-450 induced by polybrominated biphenyls. Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents."}
{"id": "PMID:23279", "title": "The disposition of threo-alpha-(2-piperidyl)-2-trifluoromethyl-6-(4-trifluoromethylphenyl)-4-pyridinemethanol phosphate in mice.", "content": "Following oral administration of the 14C-labeled title compound to male mice, the drug was well absorbed and rapidly distributed throughout the body. At least 90% of the radioactivity in the tissues at 2 hr after dosing was identified as parent compound by thin-layer chromatography. The peak plasma level of radioactivity occurred at 4 hr, and the t1/2 of elimination of parent drug was about 26 hr from the plasma and about 27 hr from the red blood cells. The major route of elimination of total radioactivity was fecal (84%), with only 5.5% in the urine at 240 hr. Only a trace of radioactivity (0.32%) was found in the expired air over a 192-hr period.", "contents": "The disposition of threo-alpha-(2-piperidyl)-2-trifluoromethyl-6-(4-trifluoromethylphenyl)-4-pyridinemethanol phosphate in mice. Following oral administration of the 14C-labeled title compound to male mice, the drug was well absorbed and rapidly distributed throughout the body. At least 90% of the radioactivity in the tissues at 2 hr after dosing was identified as parent compound by thin-layer chromatography. The peak plasma level of radioactivity occurred at 4 hr, and the t1/2 of elimination of parent drug was about 26 hr from the plasma and about 27 hr from the red blood cells. The major route of elimination of total radioactivity was fecal (84%), with only 5.5% in the urine at 240 hr. Only a trace of radioactivity (0.32%) was found in the expired air over a 192-hr period."}
{"id": "PMID:23280", "title": "Age-dependent renal accumulation of cephaloridine in the rabbit.", "content": "The accumulation of cephaloridine in the renal cortex of the rabbit was studied in vitro and in vivo in rabbits of various ages. The cortical concentration of cephaloridine, the cortex/serum ratio, and the slice/medium ratio determined by incubation of cortical slices in cephaloridine-containing media rose from birth to adult levels at approximately 1 month of age. Pretreatment with procaine penicillin G stimulated the ability to accumulate cephaloridine in vitro and in vivo. The data indicate that the lack of susceptibility of immature rabbits to cephaloridine nephrotoxicity is due to the lack of development of the anionic transport system which is apparently necessary to achieve the high cortical concentrations of cephaloridine that result in renal injury.", "contents": "Age-dependent renal accumulation of cephaloridine in the rabbit. The accumulation of cephaloridine in the renal cortex of the rabbit was studied in vitro and in vivo in rabbits of various ages. The cortical concentration of cephaloridine, the cortex/serum ratio, and the slice/medium ratio determined by incubation of cortical slices in cephaloridine-containing media rose from birth to adult levels at approximately 1 month of age. Pretreatment with procaine penicillin G stimulated the ability to accumulate cephaloridine in vitro and in vivo. The data indicate that the lack of susceptibility of immature rabbits to cephaloridine nephrotoxicity is due to the lack of development of the anionic transport system which is apparently necessary to achieve the high cortical concentrations of cephaloridine that result in renal injury."}
{"id": "PMID:23288", "title": "Nuclear-magnetic-resonance study of the histidine residues of S-peptide and S-protein and kinetics of 1H-2H exchange of ribonuclease A.", "content": "1H NMR spectroscopy at 100 MHz was used to determine the first-order rate constants for the 1H-2H exchange of the H-2 histidine resonances of RNase-A in 2H2O at 35 degrees C and pH meter readings of 7, 9, 10 and 10.5. Prolonged exposure in 2H2O at 35 degrees C and pH meter reading 11 caused irreversible denaturation of RN-ase-A. The rate constants at pH 7 and 9 agreed reasonably well with those obtained in 1H-3H exchange experiments by Ohe, J., Matsuo, H., Sakiyama, F. and Narita, K. [J. Biochem, (Tokyo) 75, 1197-1200 (1974)]. The rate data obtained by various authors is summarised and the reasons for the poor agreement between the data is discussed. The first-order rate constant for the exchange of His-48 increases rapidly from near zero at pH 9 (due to its inaccessibility to solvent) with increase of pH to 10.5 The corresponding values for His-119 show a decrease and those for His-12 a small increase over the same pH range. These changes are attributed to a conformational change in the hinge region of RNase-A (probably due to the titration of Tyr-25) which allows His-48 to become accessible to solvent. 1H NMR spectra of S-protein and S-peptide, and of material partially deuterated at the C-2 positions of the histidine residues confirm the reassignment of the histidine resonances of RNase-A [Bradbury, J. H. & Teh, J. S. (1975) Chem. Commun., 936-937]. The chemical shifts of the C-2 and C-4 protons of histidine-12 of S-peptide are followed as a function of pH and a pK' value of 6.75 is obtained. The reassignment of the three C-2 histidine resonances of S-protein is confirmed by partial deuteration studies. The pK' values obtained from titration of the H-2 resonances of His-48, His-105 and His-119 are 5.3, 6.5 and 6.0, respectively. The S-protein is less stable to acid than RNase-A since the former, but not the latter, shows evidence of reversible denaturation at pH 3 and 26 degrees C. His-48 in S-protein titrates normally and has a lower pK than in RN-ase-A probably because of the absence of Asp-14, which in RN-ase-A forms a a hydrogen bond with His-48 and causes it to be inaccessible to solvent, at pH values below 9.", "contents": "Nuclear-magnetic-resonance study of the histidine residues of S-peptide and S-protein and kinetics of 1H-2H exchange of ribonuclease A. 1H NMR spectroscopy at 100 MHz was used to determine the first-order rate constants for the 1H-2H exchange of the H-2 histidine resonances of RNase-A in 2H2O at 35 degrees C and pH meter readings of 7, 9, 10 and 10.5. Prolonged exposure in 2H2O at 35 degrees C and pH meter reading 11 caused irreversible denaturation of RN-ase-A. The rate constants at pH 7 and 9 agreed reasonably well with those obtained in 1H-3H exchange experiments by Ohe, J., Matsuo, H., Sakiyama, F. and Narita, K. [J. Biochem, (Tokyo) 75, 1197-1200 (1974)]. The rate data obtained by various authors is summarised and the reasons for the poor agreement between the data is discussed. The first-order rate constant for the exchange of His-48 increases rapidly from near zero at pH 9 (due to its inaccessibility to solvent) with increase of pH to 10.5 The corresponding values for His-119 show a decrease and those for His-12 a small increase over the same pH range. These changes are attributed to a conformational change in the hinge region of RNase-A (probably due to the titration of Tyr-25) which allows His-48 to become accessible to solvent. 1H NMR spectra of S-protein and S-peptide, and of material partially deuterated at the C-2 positions of the histidine residues confirm the reassignment of the histidine resonances of RNase-A [Bradbury, J. H. & Teh, J. S. (1975) Chem. Commun., 936-937]. The chemical shifts of the C-2 and C-4 protons of histidine-12 of S-peptide are followed as a function of pH and a pK' value of 6.75 is obtained. The reassignment of the three C-2 histidine resonances of S-protein is confirmed by partial deuteration studies. The pK' values obtained from titration of the H-2 resonances of His-48, His-105 and His-119 are 5.3, 6.5 and 6.0, respectively. The S-protein is less stable to acid than RNase-A since the former, but not the latter, shows evidence of reversible denaturation at pH 3 and 26 degrees C. His-48 in S-protein titrates normally and has a lower pK than in RN-ase-A probably because of the absence of Asp-14, which in RN-ase-A forms a a hydrogen bond with His-48 and causes it to be inaccessible to solvent, at pH values below 9."}
{"id": "PMID:23290", "title": "Subcellular distribution of a factor inactivating tyrosine aminotransferase. Study of its mechanism and relationship to different forms of the enzyme.", "content": "The subcellular distribution of a tyrosine aminotransferase inactivating factor in rat liver has been investigated. Most of its activity is associated with plasma membranes, with minor amounts in mitochondria and endoplasmatic reticulum. The factor is also found in kidney and inactivates the enzyme reversibly in presence of cysteine, most likely by modification of -SH groups. ATP counteracts this inactivation only, when crude enzyme extracts are inactivated by purified subcellular fractions or when the purified enzyme is inactivated in presence of liver or kidney cortex homogenates. The relationship of this inactivation to reported different forms of the enzyme has been investigated. Form I of three different forms, that can be obtained by hydroxyl-apatite chromatography, is readily inactivated, form III can be partly converted to form I by incubation in presence of purified plasma membranes. The relationship of these findings to a possible multistep mechanism in the turnover of the enzyme discussed.", "contents": "Subcellular distribution of a factor inactivating tyrosine aminotransferase. Study of its mechanism and relationship to different forms of the enzyme. The subcellular distribution of a tyrosine aminotransferase inactivating factor in rat liver has been investigated. Most of its activity is associated with plasma membranes, with minor amounts in mitochondria and endoplasmatic reticulum. The factor is also found in kidney and inactivates the enzyme reversibly in presence of cysteine, most likely by modification of -SH groups. ATP counteracts this inactivation only, when crude enzyme extracts are inactivated by purified subcellular fractions or when the purified enzyme is inactivated in presence of liver or kidney cortex homogenates. The relationship of this inactivation to reported different forms of the enzyme has been investigated. Form I of three different forms, that can be obtained by hydroxyl-apatite chromatography, is readily inactivated, form III can be partly converted to form I by incubation in presence of purified plasma membranes. The relationship of these findings to a possible multistep mechanism in the turnover of the enzyme discussed."}
{"id": "PMID:23291", "title": "The interrelations between the transport of sodium and calcium in mitochondria of various mammalian tissues.", "content": "Addition of ruthenium red to mitochondria isolated from brain, adrenal cortex, parotid gland and skeletal muscle inhibits further uptake of Ca2+ by these mitochondria but induces little or no net Ca2+ efflux; the further addition of Na+, however, induces rapid efflux of Ca2+. The velocity of the Na+-induced efflux of Ca2+ from these mitochondria exhibits a sigmoidal dependence on the [Na+]. Addition of Na+ to mitochondria exhibiting the most active Na+-dependent efflux of Ca2+ (brain and adrenal cortex) also releases Ca2+ in the absence of ruthenium red and, under these conditions, the mitochondria become uncoupled. It is concluded that the efflux of Ca2+ from these mitochondria occurs via a Na+-dependent pathway, possibly a Na+-Ca2+ antiporter, that is distinct from the ruthenium-red-sensitive carrier that catalyses energy-linked Ca2+-influx. The possible role of the Na+-dependent efflux process in the distribution of Ca2+ between the mitochondria and the cytosol is discussed. In contrast, mitochondria from liver, kidney, lung, uterus muscle and ileum muscle exhibit no Na+-dependent efflux of Ca2+.", "contents": "The interrelations between the transport of sodium and calcium in mitochondria of various mammalian tissues. Addition of ruthenium red to mitochondria isolated from brain, adrenal cortex, parotid gland and skeletal muscle inhibits further uptake of Ca2+ by these mitochondria but induces little or no net Ca2+ efflux; the further addition of Na+, however, induces rapid efflux of Ca2+. The velocity of the Na+-induced efflux of Ca2+ from these mitochondria exhibits a sigmoidal dependence on the [Na+]. Addition of Na+ to mitochondria exhibiting the most active Na+-dependent efflux of Ca2+ (brain and adrenal cortex) also releases Ca2+ in the absence of ruthenium red and, under these conditions, the mitochondria become uncoupled. It is concluded that the efflux of Ca2+ from these mitochondria occurs via a Na+-dependent pathway, possibly a Na+-Ca2+ antiporter, that is distinct from the ruthenium-red-sensitive carrier that catalyses energy-linked Ca2+-influx. The possible role of the Na+-dependent efflux process in the distribution of Ca2+ between the mitochondria and the cytosol is discussed. In contrast, mitochondria from liver, kidney, lung, uterus muscle and ileum muscle exhibit no Na+-dependent efflux of Ca2+."}
{"id": "PMID:23292", "title": "Induction and 'superinduction' of sialylation of membrane-bound gamma-glutamyltransferase during liver regeneration.", "content": "The present paper shows that in the regenerating rat liver the membrane-bound-gamma-glutamyltransferase exists in two molecular forms. Depending on the state of proliferation, a sialic-acid-rich enzyme (in the fetal or regenerating liver) or a sialic-acid-poor enzyme (in the adult or quiescent liver) could be detected. In regeneration liver (24 h after 2/3 resection) only the sialic-acid-rich or fetal enzyme could be found. Since total enzyme activity (adult + fetal type) remained unchanged, it is assumed that the adult type of gamma-glutamyltransferase was modified by sialylation during the initial phase of liver regeneration. This process of sialylation was prevented by inhibitors of RNA or protein synthesis such as D-galactosamine, actinomycin D or cycloheximide, provided that the inhibitor (D-galactosamine) was given within the first 8 h after partial hepatectomy. Sialylation was not impaired by inhibitors of DNA synthesis, e.g. hydroxyurea or cytosine arabinoside. Administration of actinomycin D during a defined phase of proliferation (24 to 48 h after partial hepatectomy) stimulated the transfer of sialic acid to gamma-glutamyltransferase, a finding which describes for the first time the so-called 'superinduction' of a sialylation process.", "contents": "Induction and 'superinduction' of sialylation of membrane-bound gamma-glutamyltransferase during liver regeneration. The present paper shows that in the regenerating rat liver the membrane-bound-gamma-glutamyltransferase exists in two molecular forms. Depending on the state of proliferation, a sialic-acid-rich enzyme (in the fetal or regenerating liver) or a sialic-acid-poor enzyme (in the adult or quiescent liver) could be detected. In regeneration liver (24 h after 2/3 resection) only the sialic-acid-rich or fetal enzyme could be found. Since total enzyme activity (adult + fetal type) remained unchanged, it is assumed that the adult type of gamma-glutamyltransferase was modified by sialylation during the initial phase of liver regeneration. This process of sialylation was prevented by inhibitors of RNA or protein synthesis such as D-galactosamine, actinomycin D or cycloheximide, provided that the inhibitor (D-galactosamine) was given within the first 8 h after partial hepatectomy. Sialylation was not impaired by inhibitors of DNA synthesis, e.g. hydroxyurea or cytosine arabinoside. Administration of actinomycin D during a defined phase of proliferation (24 to 48 h after partial hepatectomy) stimulated the transfer of sialic acid to gamma-glutamyltransferase, a finding which describes for the first time the so-called 'superinduction' of a sialylation process."}
{"id": "PMID:23293", "title": "On the mechanism of substrate binding to the purine-transport system of Saccharomyces cerevisiae.", "content": "The yeast Saccharomyces cerevisiae takes up adenine, guanine, hypoxanthine, and cytosine via a common energy-dependent transport system. The apparent affinity of the transport system to these and other purines and pyrimidines is correlated with their capability to be protonated to the positively charged form. Further organic molecules are competitive inhibitors when they are cationic, e.g. guanidine and octylguanidine in contrast to urea, or hexadecyltrimethylammonium in contrast to dodecylsulfate and Triton X-100. The influence of the pH on the kinetic constants of hypoxanthine transport points to a stoichiometry of one proton being associated to the transport system together with one substrate molecule. The pKa values of two ionizable groups that are involved in substrate binding are revealed; one of which (pKa = 1.8) may be attributed to the substrate, the other (pKa = 5.1) to an amino acid residue in the recognition site of the transport system. Studies with group-specific inhibitors indicate that this amino acid residue contains a carboxyl group. The results are in accordance with the assumption that a carboxyl group of the transport system, a proton and a substrate molecule arrange to an uncharged ternary complex.", "contents": "On the mechanism of substrate binding to the purine-transport system of Saccharomyces cerevisiae. The yeast Saccharomyces cerevisiae takes up adenine, guanine, hypoxanthine, and cytosine via a common energy-dependent transport system. The apparent affinity of the transport system to these and other purines and pyrimidines is correlated with their capability to be protonated to the positively charged form. Further organic molecules are competitive inhibitors when they are cationic, e.g. guanidine and octylguanidine in contrast to urea, or hexadecyltrimethylammonium in contrast to dodecylsulfate and Triton X-100. The influence of the pH on the kinetic constants of hypoxanthine transport points to a stoichiometry of one proton being associated to the transport system together with one substrate molecule. The pKa values of two ionizable groups that are involved in substrate binding are revealed; one of which (pKa = 1.8) may be attributed to the substrate, the other (pKa = 5.1) to an amino acid residue in the recognition site of the transport system. Studies with group-specific inhibitors indicate that this amino acid residue contains a carboxyl group. The results are in accordance with the assumption that a carboxyl group of the transport system, a proton and a substrate molecule arrange to an uncharged ternary complex."}
{"id": "PMID:23295", "title": "Haemodynamic response to graded exercise during chronic beta-adrenergic blockade with bunitrolol, an agent with intrinsic sympathomimetic activity.", "content": "The effect of chronic beta blockade on the haemodynamic response to graded exercise was studied in 18 hypertensive patients treated with bunitrolol, which has partial agonist activity. The patients first received a placebo for 5 to 12 days, then bunitrolol 30 mg daily for one week and subsequently the dose was doubled weekly as necessary up to 240 mg daily. At rest haemodynamic changes after beta blockade were only minor; heart rate decreased by 8% and no significant change was observed in stroke index, cardiac index, (a-v)O2 difference and VO2. The hypotensive effect was not significant and no significant change in mean pulmonary arterial and wedge pressure was observed. Maximal exercise capacity remained unchanged, because of haemodynamic responses. The maximal exercise heart rate was reduced by 25% during beta blockade, which was compensated by a 34% elevation in stroke index, whereas maximal cardiac index and (a-v)O2 difference remained unchanged. There was no consistent change in mean pulmonary artery pressure during maximal exercise, but the mean brachial artery pressure fell by 12%.", "contents": "Haemodynamic response to graded exercise during chronic beta-adrenergic blockade with bunitrolol, an agent with intrinsic sympathomimetic activity. The effect of chronic beta blockade on the haemodynamic response to graded exercise was studied in 18 hypertensive patients treated with bunitrolol, which has partial agonist activity. The patients first received a placebo for 5 to 12 days, then bunitrolol 30 mg daily for one week and subsequently the dose was doubled weekly as necessary up to 240 mg daily. At rest haemodynamic changes after beta blockade were only minor; heart rate decreased by 8% and no significant change was observed in stroke index, cardiac index, (a-v)O2 difference and VO2. The hypotensive effect was not significant and no significant change in mean pulmonary arterial and wedge pressure was observed. Maximal exercise capacity remained unchanged, because of haemodynamic responses. The maximal exercise heart rate was reduced by 25% during beta blockade, which was compensated by a 34% elevation in stroke index, whereas maximal cardiac index and (a-v)O2 difference remained unchanged. There was no consistent change in mean pulmonary artery pressure during maximal exercise, but the mean brachial artery pressure fell by 12%."}
{"id": "PMID:23296", "title": "Circadian rhythm of urinary pH in man with and without chronic antacid administration.", "content": "In normal human volunteers, when urinary pH was plotted versus time, the circadian sine-wave type curve was not altered by chronic administration of a commercially available suspension containing a mixture of magnesium and aluminum hydroxides, although the antacid perturbed the entire curve in a more alkaline direction. A single dose of the antacid had little effect on urinary pH. There was a highly significant linear relationship between the change in hydrogen ion concentration during chronic antacid treatment and the initial control urinary hydrogen ion concentration, but there was no significant correlation between change in urinary pH and initial control urinary pH as has been previously reported. The above results were based on the evaluation of the hydrogen ion concentrations of 1562 separate urine samples collected from 24 normal subjects in a three treatment crossover study. It is recommended that: (1) research studies involving drug-drug interactions with antacids be designed to consider the effect of the antacid on the circadian rhythm of urinary pH, and (2) pH values not be averaged as commonly reported in the literature, but rather the pH values be converted to hydrogen ion concentrations before statistical analysis.", "contents": "Circadian rhythm of urinary pH in man with and without chronic antacid administration. In normal human volunteers, when urinary pH was plotted versus time, the circadian sine-wave type curve was not altered by chronic administration of a commercially available suspension containing a mixture of magnesium and aluminum hydroxides, although the antacid perturbed the entire curve in a more alkaline direction. A single dose of the antacid had little effect on urinary pH. There was a highly significant linear relationship between the change in hydrogen ion concentration during chronic antacid treatment and the initial control urinary hydrogen ion concentration, but there was no significant correlation between change in urinary pH and initial control urinary pH as has been previously reported. The above results were based on the evaluation of the hydrogen ion concentrations of 1562 separate urine samples collected from 24 normal subjects in a three treatment crossover study. It is recommended that: (1) research studies involving drug-drug interactions with antacids be designed to consider the effect of the antacid on the circadian rhythm of urinary pH, and (2) pH values not be averaged as commonly reported in the literature, but rather the pH values be converted to hydrogen ion concentrations before statistical analysis."}
{"id": "PMID:23297", "title": "Antidiuresis induced by beta1- and beta2-adrenergic agonists in ethanol-anesthetized rats.", "content": "The beta1- and beta2-components in antidiuresis and sodium retention induced by beta-adrenergic agonists were analysed in ethanol-anesthetized, water-diuretic rats. Intravenous infusions of isoprenaline, salbutamol and carbuterol did not affect insulin clearance but increased plasma renin concentration to the same same extent. Propranolol completely blocked the decreases in urine volume (V) and urinary sodium excretion (UNaV) induced by isoprenaline; practolol (beta1-blocker) inhibited only the decrease in UNaV and butaxamine (beta2-blocker) inhibited only the decrease in V. The ratios of doses of beta-agonists which decreased UNaV and by 50% (ED50 UNaV decrease/ED50 V decrease) were 0.34, 0.68, 1.56 and 2.36 for isoprenaline, tretoquinol, salbutamol and carbuterol, respectively. This increasing order of the ratios coincided with the order reported for the preponderance of the beta2- over beta1-component of these agonists. These results indicate that the decrease in UNaV induced by beta-agonists is related to beta1 stimulation, while the decrease in V is related to beta2 stimulation.", "contents": "Antidiuresis induced by beta1- and beta2-adrenergic agonists in ethanol-anesthetized rats. The beta1- and beta2-components in antidiuresis and sodium retention induced by beta-adrenergic agonists were analysed in ethanol-anesthetized, water-diuretic rats. Intravenous infusions of isoprenaline, salbutamol and carbuterol did not affect insulin clearance but increased plasma renin concentration to the same same extent. Propranolol completely blocked the decreases in urine volume (V) and urinary sodium excretion (UNaV) induced by isoprenaline; practolol (beta1-blocker) inhibited only the decrease in UNaV and butaxamine (beta2-blocker) inhibited only the decrease in V. The ratios of doses of beta-agonists which decreased UNaV and by 50% (ED50 UNaV decrease/ED50 V decrease) were 0.34, 0.68, 1.56 and 2.36 for isoprenaline, tretoquinol, salbutamol and carbuterol, respectively. This increasing order of the ratios coincided with the order reported for the preponderance of the beta2- over beta1-component of these agonists. These results indicate that the decrease in UNaV induced by beta-agonists is related to beta1 stimulation, while the decrease in V is related to beta2 stimulation."}
{"id": "PMID:23298", "title": "Effects of baclofen on dopamine metabolism and interaction with neuroleptic effects.", "content": "Baclofen increased striatal levels of dopamine (DA), homovanillic (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) dose-dependently above 10 mg/kg i.p. The effect on the DA metabolites was shown to be caused only by the (-)-isomer. The HVA increase after 20 mg/kg i.p. was not antagonized by either scopolamine or picrotoxin. Repeated treatment produced a smaller increase in HVA than a single administration. Baclofen reduced both the disappearance of DA after alpha-methyl-p-tyrosine and the acceleration of the DA disappearance caused by neuroleptics in corpus striatum and in the mesolimbic area. The neuroleptic-induced increases in HVA and DOPAC and in DOPA accumulation after central decarboxylase inhibition were also reduced. Picrotoxin could not antagonize these effects of baclofen which therefore cannot be regarded as being garbergic. Baclofen effects on DA metabolism are similar to those reported for gamma-hydroxybutyric acid and are probably a consequence of inhibition of firing of DA neurons.", "contents": "Effects of baclofen on dopamine metabolism and interaction with neuroleptic effects. Baclofen increased striatal levels of dopamine (DA), homovanillic (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) dose-dependently above 10 mg/kg i.p. The effect on the DA metabolites was shown to be caused only by the (-)-isomer. The HVA increase after 20 mg/kg i.p. was not antagonized by either scopolamine or picrotoxin. Repeated treatment produced a smaller increase in HVA than a single administration. Baclofen reduced both the disappearance of DA after alpha-methyl-p-tyrosine and the acceleration of the DA disappearance caused by neuroleptics in corpus striatum and in the mesolimbic area. The neuroleptic-induced increases in HVA and DOPAC and in DOPA accumulation after central decarboxylase inhibition were also reduced. Picrotoxin could not antagonize these effects of baclofen which therefore cannot be regarded as being garbergic. Baclofen effects on DA metabolism are similar to those reported for gamma-hydroxybutyric acid and are probably a consequence of inhibition of firing of DA neurons."}
{"id": "PMID:23300", "title": "Inhibition of somato-sympathetic reflex via peripheral presynaptic alha-adrenoceptors.", "content": "In cats anaesthetized with chloralose--urethane (70/100 mg/kg) a somato-sympathetic reflex increase of blood pressure and heart rate was evoked by electrical stimulation of sensory fibres running within the tibial nerve. I.V. injection of 30 microgram/kg of the alpha-adrenoceptor agonist clonidine caused a reflex inhibition in intact and vagotomized animals. In contrast, injection of 2 microgram/kg clonidine into the vertebral artery elicited hypotension but no reflux inhibition. In small doses, phenylephrine which is known from in vitro experiments to prefer the postsynaptic alpha-adrenoceptor, potentiated the reflex increase in blood pressure by an additive effect on the vascular alpha-adrenoceptor, while oxymetazoline and tramazoline, which preferentially activate the presynaptic receptor, were inhibitory. The inhibitory effect of tramazoline on the reflex increase in blood pressure and heart rate was antagonized by the presynaptic alpha-adrenolytic drug yohimbine. The results suggest that peripheral presynaptic alpha-adrenoceptors are responsible for somato-sympathetic reflex inhibition. The importance of peripheral presynaptic alpha-adrenoceptors in the in vivo regulation of blood pressure is discussed.", "contents": "Inhibition of somato-sympathetic reflex via peripheral presynaptic alha-adrenoceptors. In cats anaesthetized with chloralose--urethane (70/100 mg/kg) a somato-sympathetic reflex increase of blood pressure and heart rate was evoked by electrical stimulation of sensory fibres running within the tibial nerve. I.V. injection of 30 microgram/kg of the alpha-adrenoceptor agonist clonidine caused a reflex inhibition in intact and vagotomized animals. In contrast, injection of 2 microgram/kg clonidine into the vertebral artery elicited hypotension but no reflux inhibition. In small doses, phenylephrine which is known from in vitro experiments to prefer the postsynaptic alpha-adrenoceptor, potentiated the reflex increase in blood pressure by an additive effect on the vascular alpha-adrenoceptor, while oxymetazoline and tramazoline, which preferentially activate the presynaptic receptor, were inhibitory. The inhibitory effect of tramazoline on the reflex increase in blood pressure and heart rate was antagonized by the presynaptic alpha-adrenolytic drug yohimbine. The results suggest that peripheral presynaptic alpha-adrenoceptors are responsible for somato-sympathetic reflex inhibition. The importance of peripheral presynaptic alpha-adrenoceptors in the in vivo regulation of blood pressure is discussed."}
{"id": "PMID:23301", "title": "Chronic effects of nicotine on catecholamine synthesizing enzymes in rats.", "content": "The effects of chronic administration of nicotine upon catecholamine (CA) synthesizing enzymes of rat hypothalamus, striatum and adrenal medulla were studied. Nicotine 3 mg/kg/day for 14 days, increased tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) in hypothalamus and adrenal medulla but did change striatum TH. The data suggest that chronic nicotine administration can produce similar long-term alterations in both of the main CA forming enzymes in the hypothalamus and in adrenal medulla.", "contents": "Chronic effects of nicotine on catecholamine synthesizing enzymes in rats. The effects of chronic administration of nicotine upon catecholamine (CA) synthesizing enzymes of rat hypothalamus, striatum and adrenal medulla were studied. Nicotine 3 mg/kg/day for 14 days, increased tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) in hypothalamus and adrenal medulla but did change striatum TH. The data suggest that chronic nicotine administration can produce similar long-term alterations in both of the main CA forming enzymes in the hypothalamus and in adrenal medulla."}
{"id": "PMID:23306", "title": "[The usefulness of ruthenium red in dye exclusion test on cultured cells (author's transl)].", "content": "The reliability of statements and the reproducibility of results derived from experiments on cell cultures are dependent on the use of practicable methods for most objective assay of the state of the cells. The experiments were to clarify the following questions: 1. Is it possible to assay vital and nonvital cells by use of the dye exclusion test (FET)? 2. Are intact cells also stained by FET? 3. Will there be a possibility to make FET more sensitive to obtain more reliable statements?", "contents": "[The usefulness of ruthenium red in dye exclusion test on cultured cells (author's transl)]. The reliability of statements and the reproducibility of results derived from experiments on cell cultures are dependent on the use of practicable methods for most objective assay of the state of the cells. The experiments were to clarify the following questions: 1. Is it possible to assay vital and nonvital cells by use of the dye exclusion test (FET)? 2. Are intact cells also stained by FET? 3. Will there be a possibility to make FET more sensitive to obtain more reliable statements?"}
{"id": "PMID:23321", "title": "Testicular germ cell differentiation in vivo.", "content": "The effects of artificial cryptorchidism and surgical reversal on spermatogenesis were examined in mice. Only undifferentiated type A spermatogonia were present as germ cells in cryptorchid testes. The surgical reversal of cryptorchidism resulted in regenerative differentiation of mature germ cells as judged by testicular weight, histologic examination, and increase in the specific activity of lactate dehydrogenase-X. Leydig cell function was also examined by assessment of the weight of target tissues of androgen. They showed a unique change following the surgical reversal. Thirty days after surgical reversal, hyperfunction of the Leydig cells was observed, and the testes became normal after 60 days.", "contents": "Testicular germ cell differentiation in vivo. The effects of artificial cryptorchidism and surgical reversal on spermatogenesis were examined in mice. Only undifferentiated type A spermatogonia were present as germ cells in cryptorchid testes. The surgical reversal of cryptorchidism resulted in regenerative differentiation of mature germ cells as judged by testicular weight, histologic examination, and increase in the specific activity of lactate dehydrogenase-X. Leydig cell function was also examined by assessment of the weight of target tissues of androgen. They showed a unique change following the surgical reversal. Thirty days after surgical reversal, hyperfunction of the Leydig cells was observed, and the testes became normal after 60 days."}
{"id": "PMID:23322", "title": "[Relationship between the anionic structure of organic acids and the response of cat taste receptors].", "content": "With the aid of analysis of afferent impulse activity in the cat chorda tympani, it was shown that the effect of application of organic acids solutions of the same pH to the tongue could be represented as follows: propionic acid greater than lactic acid greater than pyruvic acid. These data confirm the suggestion that carboxylic acids without polar groups are the most effective, and an anion which has OH-group in alpha-position is more effective than an anion with keto-group.", "contents": "[Relationship between the anionic structure of organic acids and the response of cat taste receptors]. With the aid of analysis of afferent impulse activity in the cat chorda tympani, it was shown that the effect of application of organic acids solutions of the same pH to the tongue could be represented as follows: propionic acid greater than lactic acid greater than pyruvic acid. These data confirm the suggestion that carboxylic acids without polar groups are the most effective, and an anion which has OH-group in alpha-position is more effective than an anion with keto-group."}
{"id": "PMID:23331", "title": "Molecular biology and molecular pathology of a newly described molecular disease--tyrosinemia II (the Richner-Hanhart syndrome).", "content": "A deficiency of hepatic tyrosine aminotransferase in humans is responsible for a syndrome of keratitis, palmar and plantar erosions and hyperkeratosis and mental retardation. Serum tyrosine increases due to the enzymatic deficiency leads to the deposition of tyrosine crystals in the eye and cornea. This deposition and possible lysosomal activation leads to inflammation in the cornea and the skin. The syndrome can be reproduced in animals who are fed a high tyrosine diet. The interaction of tyrosine crystals with membrane-bound particles can be studied in vitro with lysosomes and erythrocytes.", "contents": "Molecular biology and molecular pathology of a newly described molecular disease--tyrosinemia II (the Richner-Hanhart syndrome). A deficiency of hepatic tyrosine aminotransferase in humans is responsible for a syndrome of keratitis, palmar and plantar erosions and hyperkeratosis and mental retardation. Serum tyrosine increases due to the enzymatic deficiency leads to the deposition of tyrosine crystals in the eye and cornea. This deposition and possible lysosomal activation leads to inflammation in the cornea and the skin. The syndrome can be reproduced in animals who are fed a high tyrosine diet. The interaction of tyrosine crystals with membrane-bound particles can be studied in vitro with lysosomes and erythrocytes."}
{"id": "PMID:23333", "title": "An in vitro study of functional maturation of murine thymus cells.", "content": "Critical time of onset of thymus cell functions in ontogeny was studied in vitro. Collaborative function in an antibody response and ability to induce a graft-versus-host (GvH) response by murine thymocytes from different stages of ontogeny were investigated. Thymocytes from as early as 16-day mouse embryos were capable of collaborating in the antibody response to sheep-erythrocyte-antigen in vitro following 24 h of pretreatment with concanavalin A (con A). By contrast, maturation of thymus cell function as measured by competence to induce a graft-versus-host reaction, was first manifested by newborn thymus cells, and pretreatment with con A did not facilitate the maturation of this thymus cell function. Experiments to understand the effect of con A on the expression of cell surface antigens have also been reported. Con A-treated thymus cells of different ontogenic stages tested were less susceptible to killing by anti-theta serum than nontreated thymus cells; reverse was true with anti-H-2 serum. The significance of the differential susceptibility of con A-treated thymus cells to anti-sera treatment and the finding that mouse thymocytes can provide helper function as early as the 16th day of gestation have been discussed.", "contents": "An in vitro study of functional maturation of murine thymus cells. Critical time of onset of thymus cell functions in ontogeny was studied in vitro. Collaborative function in an antibody response and ability to induce a graft-versus-host (GvH) response by murine thymocytes from different stages of ontogeny were investigated. Thymocytes from as early as 16-day mouse embryos were capable of collaborating in the antibody response to sheep-erythrocyte-antigen in vitro following 24 h of pretreatment with concanavalin A (con A). By contrast, maturation of thymus cell function as measured by competence to induce a graft-versus-host reaction, was first manifested by newborn thymus cells, and pretreatment with con A did not facilitate the maturation of this thymus cell function. Experiments to understand the effect of con A on the expression of cell surface antigens have also been reported. Con A-treated thymus cells of different ontogenic stages tested were less susceptible to killing by anti-theta serum than nontreated thymus cells; reverse was true with anti-H-2 serum. The significance of the differential susceptibility of con A-treated thymus cells to anti-sera treatment and the finding that mouse thymocytes can provide helper function as early as the 16th day of gestation have been discussed."}
{"id": "PMID:23334", "title": "The further investigation on the gastric acid secretion in the primary hyperparathyroidism.", "content": "The gastric acid output was studied in the 11 patients of hyperparathyroidism before and after parathyroidectomy. The gastric acid output before operation was almost equal to the normal control in our hospital. After the correction of serum calcium by parathyroidectomy, the gastric acid output and serum gastrin were decreased. The decreased gastric acid output was recovered as the days passed since operation and approached to the preoperative level. The acid output in hyperparathyroidism was less in the case whose activity of alkaline phosphatase was more, which suggested that the calcium deposition on gastric mucosa might damage the parietal cell as the result of long lasting hypercalcemia.", "contents": "The further investigation on the gastric acid secretion in the primary hyperparathyroidism. The gastric acid output was studied in the 11 patients of hyperparathyroidism before and after parathyroidectomy. The gastric acid output before operation was almost equal to the normal control in our hospital. After the correction of serum calcium by parathyroidectomy, the gastric acid output and serum gastrin were decreased. The decreased gastric acid output was recovered as the days passed since operation and approached to the preoperative level. The acid output in hyperparathyroidism was less in the case whose activity of alkaline phosphatase was more, which suggested that the calcium deposition on gastric mucosa might damage the parietal cell as the result of long lasting hypercalcemia."}
{"id": "PMID:23335", "title": "Effect of Ca2+, Mg2+, NaN3, cholinergic agents, and gastrointestinal hormones on the guanylate cyclase from guinea pig gastric mucosa.", "content": "Guanylate cyclase in the guinea pig fundic mucosa occurred in two enzymatic forms: a \"soluble\" form and a particulate form. The mean basal activity of the soluble fraction measured in the presence of 300 micrometer guanosine-5'-triphosphate and 5 mM MnCl2 was 72.6 +/- 5.3 pmoles of cyclic GMP per mg of protein per min. Guanylate cyclase activity was dependent on Mn2+; it was increased by sodium azide (NaN3), CaCl2, cysteine, secretin, and cholecystokinin, but it was not influenced by gastrin, histamine, cholinergic esters, prostaglandins E1 and A1. NaN3 (1 mM) decreased the apparent Km for MnCl2 and potentiated the effects of MgCl2. The activity of the particulate fraction represented about 14% of that of the supernatant fraction. The guanylate cyclase activity of that fraction was not modified by NaN3, gastrin, cholinergic agents, secretin, or cholecystokinin. Cysteine inhibited its activity. These data do not support the hypothesis that cyclic GMP acts as a second messenger for the action of cholinergic agents and gastrin in the guinea pig gastric mucosa.", "contents": "Effect of Ca2+, Mg2+, NaN3, cholinergic agents, and gastrointestinal hormones on the guanylate cyclase from guinea pig gastric mucosa. Guanylate cyclase in the guinea pig fundic mucosa occurred in two enzymatic forms: a \"soluble\" form and a particulate form. The mean basal activity of the soluble fraction measured in the presence of 300 micrometer guanosine-5'-triphosphate and 5 mM MnCl2 was 72.6 +/- 5.3 pmoles of cyclic GMP per mg of protein per min. Guanylate cyclase activity was dependent on Mn2+; it was increased by sodium azide (NaN3), CaCl2, cysteine, secretin, and cholecystokinin, but it was not influenced by gastrin, histamine, cholinergic esters, prostaglandins E1 and A1. NaN3 (1 mM) decreased the apparent Km for MnCl2 and potentiated the effects of MgCl2. The activity of the particulate fraction represented about 14% of that of the supernatant fraction. The guanylate cyclase activity of that fraction was not modified by NaN3, gastrin, cholinergic agents, secretin, or cholecystokinin. Cysteine inhibited its activity. These data do not support the hypothesis that cyclic GMP acts as a second messenger for the action of cholinergic agents and gastrin in the guinea pig gastric mucosa."}
{"id": "PMID:23336", "title": "Characterization and development of cimetidine as a histamine H2-receptor antagonist.", "content": "The concept of two classes of histamine receptor, H1 and H2, is introduced and the chemical derivation of histamine H2-receptor antagonists is outlined briefly. Starting from the structure of histamine, chemical modification led eventually to burimamide, the first described histamine H2-receptor antagonist. Further stepwise modifications ultimately afforded metiamide and cimetidine. In vitro studies show that cimetidine is a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in rats and dogs after both intravenous and oral administration. It is equally potent as an inhibitor of pentagastrin-stimulated secretion. The evidence suggests that cimetidine inhibits gastric acid secretion through blockade of histamine H2-receptors in the gastric mucosa. Cimetidine has been shown to have low acute toxicity. Repeated dose studies of up to 24 months in rats and up to 12 months in dogs have been carried out and the results are presented and discussed. There is no known toxic effect which would limit the usefulness of cimetidine in man.", "contents": "Characterization and development of cimetidine as a histamine H2-receptor antagonist. The concept of two classes of histamine receptor, H1 and H2, is introduced and the chemical derivation of histamine H2-receptor antagonists is outlined briefly. Starting from the structure of histamine, chemical modification led eventually to burimamide, the first described histamine H2-receptor antagonist. Further stepwise modifications ultimately afforded metiamide and cimetidine. In vitro studies show that cimetidine is a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in rats and dogs after both intravenous and oral administration. It is equally potent as an inhibitor of pentagastrin-stimulated secretion. The evidence suggests that cimetidine inhibits gastric acid secretion through blockade of histamine H2-receptors in the gastric mucosa. Cimetidine has been shown to have low acute toxicity. Repeated dose studies of up to 24 months in rats and up to 12 months in dogs have been carried out and the results are presented and discussed. There is no known toxic effect which would limit the usefulness of cimetidine in man."}
{"id": "PMID:23338", "title": "Effect of H2-receptor antagonists on gastric acid secretion and serum gastrin concentration: a review.", "content": "Cimetidine inhibits basal and nocturnal acid secretion and acid secretion stimulated by histamine, pentagastrin, caffeine, insulin, sham feeding, and food. Cinetidine (300 mg) inhibits basal acid secretion in duodenal ulcer patients by 95% for at least 5 hr. When taken at bedtime, cimetidine inhibits nocturnal acid secretion by greater than 80% for most of the night. Cimetidine markedly inhibits food-stimulated acid secretion and is more effective than anticholinergic drugs. However, to get adequate suppression of food-stimulated acid secretion throughout the day, cimetidine should be given with each meal. Cimetidine has no effect on nocturnal serum gastrin concentration, but, when stimulated by food, serum gastrin concentration is higher after cimetidine than after placebo.", "contents": "Effect of H2-receptor antagonists on gastric acid secretion and serum gastrin concentration: a review. Cimetidine inhibits basal and nocturnal acid secretion and acid secretion stimulated by histamine, pentagastrin, caffeine, insulin, sham feeding, and food. Cinetidine (300 mg) inhibits basal acid secretion in duodenal ulcer patients by 95% for at least 5 hr. When taken at bedtime, cimetidine inhibits nocturnal acid secretion by greater than 80% for most of the night. Cimetidine markedly inhibits food-stimulated acid secretion and is more effective than anticholinergic drugs. However, to get adequate suppression of food-stimulated acid secretion throughout the day, cimetidine should be given with each meal. Cimetidine has no effect on nocturnal serum gastrin concentration, but, when stimulated by food, serum gastrin concentration is higher after cimetidine than after placebo."}
{"id": "PMID:23345", "title": "Ditazole activity and its interaction with urokinase on experimental thrombosis.", "content": "The effect of ditazole, a new antiaggregant oxazole derivative as well as its possible interaction with urokinase on the formation of electrically induced thrombus, was assayed in rabbits. The activity of ditazole in reducing thrombus weight was comparable to that of aspirin. In the ditazole- or aspirin-treated animals, the microscopical examination of the thrombus showed a reduction in the fibrin component, and well-isolated platelets not undergoing a viscous metamorphosis were present. Urokinase, administered in combination with these antiaggregant drugs, did not induce a further reduction in thrombus weight. However, this additional treatment did induce clearly visible lytic areas and histological modifications as observed with the antiaggregant drugs. These data suggest that the antiplatelet drug ditazole may be an effective antithrombotic agent in man and could facilitate the penetration of urokinase into the thrombus.", "contents": "Ditazole activity and its interaction with urokinase on experimental thrombosis. The effect of ditazole, a new antiaggregant oxazole derivative as well as its possible interaction with urokinase on the formation of electrically induced thrombus, was assayed in rabbits. The activity of ditazole in reducing thrombus weight was comparable to that of aspirin. In the ditazole- or aspirin-treated animals, the microscopical examination of the thrombus showed a reduction in the fibrin component, and well-isolated platelets not undergoing a viscous metamorphosis were present. Urokinase, administered in combination with these antiaggregant drugs, did not induce a further reduction in thrombus weight. However, this additional treatment did induce clearly visible lytic areas and histological modifications as observed with the antiaggregant drugs. These data suggest that the antiplatelet drug ditazole may be an effective antithrombotic agent in man and could facilitate the penetration of urokinase into the thrombus."}
{"id": "PMID:23346", "title": "[Inhibitory effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system (author's transl)].", "content": "Effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system in mice, rats and cats were investigated, and a comparison was made with such effects of reserpine and rescinamine. Inhibitory effects of CD-3400 on spontaneous motor activity and conditioned avoidance response were weaker and shorter than those of reserpine and rescinnamine. In the experiments of the inhibitory effects of the central actions such as ptosis, hypothermia, decrease in motor ability, potentiation of hexobarbital and taming, reserpine was found to be the most potent followed by rescinnamine and CD-3400, respectively. High doses of CD-3400 exhibited inhibitory effects on methamphetamine-induced hyperactivity in mice and this action was weaker than those of reserpine and rescinnamine. CD-3400, 80-160 mg/kg p.o., showed no significant effects on morphine-induced analgesia, while a slight inhibition was observed on the Straub-tail reaction using morphine. Reserpine, 0.5 mg/kg i.v., resulted in a drowsy pattern in the spontaneous EEG activity and the EEG arousal response was depressed, while with CD-3400, 5 mg/kg i.v., there was no drowsy pattern. CD-3400 as well as rescinnamine and reserpine remarkably depleted 5-HT levels in brain, heart and plasma and the potency of CD-3400, particularly in the brain, was weaker than the potency of reserpine and rescinnamine. These results indicate that CD-3400 is an antihypertensive agent with a low toxicity and a weak central action.", "contents": "[Inhibitory effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system (author's transl)]. Effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system in mice, rats and cats were investigated, and a comparison was made with such effects of reserpine and rescinamine. Inhibitory effects of CD-3400 on spontaneous motor activity and conditioned avoidance response were weaker and shorter than those of reserpine and rescinnamine. In the experiments of the inhibitory effects of the central actions such as ptosis, hypothermia, decrease in motor ability, potentiation of hexobarbital and taming, reserpine was found to be the most potent followed by rescinnamine and CD-3400, respectively. High doses of CD-3400 exhibited inhibitory effects on methamphetamine-induced hyperactivity in mice and this action was weaker than those of reserpine and rescinnamine. CD-3400, 80-160 mg/kg p.o., showed no significant effects on morphine-induced analgesia, while a slight inhibition was observed on the Straub-tail reaction using morphine. Reserpine, 0.5 mg/kg i.v., resulted in a drowsy pattern in the spontaneous EEG activity and the EEG arousal response was depressed, while with CD-3400, 5 mg/kg i.v., there was no drowsy pattern. CD-3400 as well as rescinnamine and reserpine remarkably depleted 5-HT levels in brain, heart and plasma and the potency of CD-3400, particularly in the brain, was weaker than the potency of reserpine and rescinnamine. These results indicate that CD-3400 is an antihypertensive agent with a low toxicity and a weak central action."}
{"id": "PMID:23347", "title": "[High risk groups for gastrointestinal carcinoma].", "content": "High-risk groups for gastrointestinal carcinoma are heterogenic in regard to etiopathology; familial predisposition and genetic defects (familial adenomatosis coli, tylosis palmaris et plantaris, Gardner syndrome, Peutz-Jeghers syndrome), occupational factors (asbestor exposure), surgical intervention (resected stomach, ureterosigmoidostomy), long lasting passage obstruction (oesophagus) or chronic inflammatory alteration of the mucosa (pernicious anemia, ulcerative colitis, Crohn's disease, glutenenteropathy). Although high-risk groups account only for about 5 per cent of all carcinomas, consequent follow-up examinations of these small collectives offer early diagnosis of carcinoma at a curable stage.", "contents": "[High risk groups for gastrointestinal carcinoma]. High-risk groups for gastrointestinal carcinoma are heterogenic in regard to etiopathology; familial predisposition and genetic defects (familial adenomatosis coli, tylosis palmaris et plantaris, Gardner syndrome, Peutz-Jeghers syndrome), occupational factors (asbestor exposure), surgical intervention (resected stomach, ureterosigmoidostomy), long lasting passage obstruction (oesophagus) or chronic inflammatory alteration of the mucosa (pernicious anemia, ulcerative colitis, Crohn's disease, glutenenteropathy). Although high-risk groups account only for about 5 per cent of all carcinomas, consequent follow-up examinations of these small collectives offer early diagnosis of carcinoma at a curable stage."}
{"id": "PMID:23348", "title": "[Precancerous lesions in the gastrointestinal tract].", "content": "In the large intestine, the pathologist has to differentiate between multiple polyps and polyposis (more than 100 polyps), further between adenomatosis (coli) and non-neoplastic (tumorlike) polyposis. Without prophylactic colectomy, in about 80% of adenomatosis patients an evolution of cancer is observed. Patients with extensive or total ulcerative colitis and a long history have an increased risk for developing carcinoma. Precancerous dysplasia can be demonstrated in rectoscopic and/or colonoscopic biopsies. Cancers complicating adenomatosis or ulcerative colitis account for only a very small proportion of large bowel carcinoma. The \"adenoma-cancer sequence\" is of greater importance. Colorectal polyps should be removed endoscopically whenever possible. Most gastric polyps are non-neoplastic and have no carcinomatous potential. The true adenoma and the so-called borderline lesion only can be considered as precursor of the gastric carcinoma.", "contents": "[Precancerous lesions in the gastrointestinal tract]. In the large intestine, the pathologist has to differentiate between multiple polyps and polyposis (more than 100 polyps), further between adenomatosis (coli) and non-neoplastic (tumorlike) polyposis. Without prophylactic colectomy, in about 80% of adenomatosis patients an evolution of cancer is observed. Patients with extensive or total ulcerative colitis and a long history have an increased risk for developing carcinoma. Precancerous dysplasia can be demonstrated in rectoscopic and/or colonoscopic biopsies. Cancers complicating adenomatosis or ulcerative colitis account for only a very small proportion of large bowel carcinoma. The \"adenoma-cancer sequence\" is of greater importance. Colorectal polyps should be removed endoscopically whenever possible. Most gastric polyps are non-neoplastic and have no carcinomatous potential. The true adenoma and the so-called borderline lesion only can be considered as precursor of the gastric carcinoma."}
{"id": "PMID:23351", "title": "Drug refusal in schizophrenia: causes and prescribing hints.", "content": "Many discharged patients diagnosed as schizophrenic do not continue to take their prescribed antipsychotic medication. Reasons for reluctance to take drugs include the development of extrapyramidal symptoms, most notably akathisia and akinesia; a poor doctor-patient relationship; or the patient's preference to continue his schizophrenic existence. To improve drug compliance, the physician should ask the patient about his impressions of side-effects and should let the patient help determine the optimal dosage.", "contents": "Drug refusal in schizophrenia: causes and prescribing hints. Many discharged patients diagnosed as schizophrenic do not continue to take their prescribed antipsychotic medication. Reasons for reluctance to take drugs include the development of extrapyramidal symptoms, most notably akathisia and akinesia; a poor doctor-patient relationship; or the patient's preference to continue his schizophrenic existence. To improve drug compliance, the physician should ask the patient about his impressions of side-effects and should let the patient help determine the optimal dosage."}
{"id": "PMID:23352", "title": "Characterisation of purine nucleoside phosphorylase from fibroblasts using ultra-microchemical methods.", "content": "A new technique to quantitate nucleoside phosphorylase (NP) activity in single or small numbers of counted visually selected cells is presented. Fibroblasts were cultivated on the plastic film bottom of culture dishes. After lyophilisation in situ, plastic film leaflets carrying a counted number of cells were cut out and tested for NP activity. Some properties of NP, including temperature stability, pH optimum and substrate affinity, have been studied. The data obtained suggest that Np might play a regulatory role in the purine interconversion pathway.", "contents": "Characterisation of purine nucleoside phosphorylase from fibroblasts using ultra-microchemical methods. A new technique to quantitate nucleoside phosphorylase (NP) activity in single or small numbers of counted visually selected cells is presented. Fibroblasts were cultivated on the plastic film bottom of culture dishes. After lyophilisation in situ, plastic film leaflets carrying a counted number of cells were cut out and tested for NP activity. Some properties of NP, including temperature stability, pH optimum and substrate affinity, have been studied. The data obtained suggest that Np might play a regulatory role in the purine interconversion pathway."}
{"id": "PMID:23358", "title": "Bioavailability of digoxin: some pitfalls and problems.", "content": "The bioavailability of tablet formulations averages about 60% for digoxin, 75% for beta-acetyldigoxin, and 75% for beta-methyldigoxin. Bioavailability as a measure of the absolute amount reaching the systemic circulation should be calculated from steady state data. Only in steady state does the retarding effect of absorption disappear which diminishes the p.o./i.v. relation of data. For a screening test bioavailability may be calculated from 24-hour renal excretion values after a single dose, performing absolute and relative studies consecutively in cross-over arrangements. The absorption rate constant of digoxin and its derivatives is approximately 0.7 (h-1) which corresponds to an absorption half life of about 1 hour. The absorption rate constant can be calculated from plasma concentration values as well as from renal excretion rates 1 or 2 hours after dosing.", "contents": "Bioavailability of digoxin: some pitfalls and problems. The bioavailability of tablet formulations averages about 60% for digoxin, 75% for beta-acetyldigoxin, and 75% for beta-methyldigoxin. Bioavailability as a measure of the absolute amount reaching the systemic circulation should be calculated from steady state data. Only in steady state does the retarding effect of absorption disappear which diminishes the p.o./i.v. relation of data. For a screening test bioavailability may be calculated from 24-hour renal excretion values after a single dose, performing absolute and relative studies consecutively in cross-over arrangements. The absorption rate constant of digoxin and its derivatives is approximately 0.7 (h-1) which corresponds to an absorption half life of about 1 hour. The absorption rate constant can be calculated from plasma concentration values as well as from renal excretion rates 1 or 2 hours after dosing."}
{"id": "PMID:23362", "title": "[Pityriasis versicolor in Greece and its predisposition factors].", "content": "The age and seasonal incidence of 2610 patients with pityriasis versicolor in Greece were studied. Determination of the pH of Na and K ions of the sweat and the microbiol flora of the skin of pityriasis versicolor patients was undertaken. Besides these the effectiveness of a 1% selenium disulfid suspension was tested. The results indicate that the age groups of 20-29 and 30-30 years are mostly affected by the disease. A high incidence of the skin manifestation was noted during the summer and fall months. A difference of the pH of the sweat between pityriasis versicolor and healthy controls was observed, but no difference was found in the Na and K ions of the sweat among these two groups. Neither did the microbial flora from the skin lesions of patients and from corresponding sites of controls show any difference. The high relapse in this experiment indicates the relative ineffectiveness of selenium disulfid preparations when used as a 1% suspension in the treatment of pityriasis versicolor.", "contents": "[Pityriasis versicolor in Greece and its predisposition factors]. The age and seasonal incidence of 2610 patients with pityriasis versicolor in Greece were studied. Determination of the pH of Na and K ions of the sweat and the microbiol flora of the skin of pityriasis versicolor patients was undertaken. Besides these the effectiveness of a 1% selenium disulfid suspension was tested. The results indicate that the age groups of 20-29 and 30-30 years are mostly affected by the disease. A high incidence of the skin manifestation was noted during the summer and fall months. A difference of the pH of the sweat between pityriasis versicolor and healthy controls was observed, but no difference was found in the Na and K ions of the sweat among these two groups. Neither did the microbial flora from the skin lesions of patients and from corresponding sites of controls show any difference. The high relapse in this experiment indicates the relative ineffectiveness of selenium disulfid preparations when used as a 1% suspension in the treatment of pityriasis versicolor."}
{"id": "PMID:23363", "title": "Preparation of peroxisomes from carp liver by zonal rotor density gradient centrifugation.", "content": "Peroxisomes from carp liver can be separated by isopycnic density gradient centrifugation in sucrose. Without reaching complete sedimentation equilibrium, the purification by this method is quite successful. There is a 40-fold enrichment of catalase, the peroxisomal marker, with a total yield of 27%. No pretreatment of animals is necessary for separation from lysosomes, which, besides high fragility, show lower buoyant densities than peroxisomes. The enzyme content of carp liver peroxisomes is similar to that of rat liver, with the exception of alpha-glycerophosphate dehydrogenase, which in this tissue is a completely soluble cytoplasmic enzyme. Total activities are much lower than in the rat, for the characteristic peroxisomal oxidases the difference being in the range of one order of magnitude.", "contents": "Preparation of peroxisomes from carp liver by zonal rotor density gradient centrifugation. Peroxisomes from carp liver can be separated by isopycnic density gradient centrifugation in sucrose. Without reaching complete sedimentation equilibrium, the purification by this method is quite successful. There is a 40-fold enrichment of catalase, the peroxisomal marker, with a total yield of 27%. No pretreatment of animals is necessary for separation from lysosomes, which, besides high fragility, show lower buoyant densities than peroxisomes. The enzyme content of carp liver peroxisomes is similar to that of rat liver, with the exception of alpha-glycerophosphate dehydrogenase, which in this tissue is a completely soluble cytoplasmic enzyme. Total activities are much lower than in the rat, for the characteristic peroxisomal oxidases the difference being in the range of one order of magnitude."}
{"id": "PMID:23364", "title": "[Ultrastructural localization of acid and alkaline phosphatases in sterile septae of the anthozoa Pachycerianthus fimbriatus (author's transl)].", "content": "Acid and alkaline phosphatase activity has been localized in the cells of the sterile septae of starved and fed anthozoa. Acid phosphatase is present in lysosomes, in Golgi cisternae and old phagosomes of starved animals. In fed animals, the reaction is more intense and the number of lysosomes is increased. New phagosomes are loaded with lead phosphate. In starved animals, the alkaline phosphatase activity has been observed on the plasma membranes and in the old phagosomes.", "contents": "[Ultrastructural localization of acid and alkaline phosphatases in sterile septae of the anthozoa Pachycerianthus fimbriatus (author's transl)]. Acid and alkaline phosphatase activity has been localized in the cells of the sterile septae of starved and fed anthozoa. Acid phosphatase is present in lysosomes, in Golgi cisternae and old phagosomes of starved animals. In fed animals, the reaction is more intense and the number of lysosomes is increased. New phagosomes are loaded with lead phosphate. In starved animals, the alkaline phosphatase activity has been observed on the plasma membranes and in the old phagosomes."}
{"id": "PMID:23365", "title": "Ultrastructural demonstration of amine granules in the adrenal medullary cells of the rat using acid permanganate fixation.", "content": "Potassium permanganate fixative is usually employed at pH 7.0. At this pH the amines in the granules of the adrenal medullary cells do not react with permanganate. When the pH was adjusted to 5.0, electron dense precipitates were seen in the amine granules of part of the medullary cells, probably noradrenalin containing cells.", "contents": "Ultrastructural demonstration of amine granules in the adrenal medullary cells of the rat using acid permanganate fixation. Potassium permanganate fixative is usually employed at pH 7.0. At this pH the amines in the granules of the adrenal medullary cells do not react with permanganate. When the pH was adjusted to 5.0, electron dense precipitates were seen in the amine granules of part of the medullary cells, probably noradrenalin containing cells."}
{"id": "PMID:23371", "title": "Retrospective study of 350 cases of equine cryptorchidism.", "content": "Equine cryptorchidism was examined by a review of the literature and a retrospective study of 350 horses over a 14-year period. The incidence of left vs right testis retention was nearly equal. On the left side, 75.2% of the retained testes were retained abdominally and 24.8% inguinally; on the right side, 41.8% of the retained testes were retained abdominally and 58.2% inguinally. Preoperative diagnosis by rectal palpation of the vaginal rings was considered a valuable technique, with 87.9% accuracy in 190 horses. Invasive and nonivasive surgical techniques for abdominal cryptorchidectomy and associated complications were compared. The results supported the technique of traction on gonadal structures outside the abdominal cavity (noninvasive) as superior to techniques requiring intraabdominal manipulation (invasive).", "contents": "Retrospective study of 350 cases of equine cryptorchidism. Equine cryptorchidism was examined by a review of the literature and a retrospective study of 350 horses over a 14-year period. The incidence of left vs right testis retention was nearly equal. On the left side, 75.2% of the retained testes were retained abdominally and 24.8% inguinally; on the right side, 41.8% of the retained testes were retained abdominally and 58.2% inguinally. Preoperative diagnosis by rectal palpation of the vaginal rings was considered a valuable technique, with 87.9% accuracy in 190 horses. Invasive and nonivasive surgical techniques for abdominal cryptorchidectomy and associated complications were compared. The results supported the technique of traction on gonadal structures outside the abdominal cavity (noninvasive) as superior to techniques requiring intraabdominal manipulation (invasive)."}
{"id": "PMID:23372", "title": "Occurrence and distribution of western equine encephalomyelitis in Florida.", "content": "Research and surveillance programs relating to the occurrence and distribution of western equine encephalomyelitis virus in Florida, conducted between 1955 and 1976, suggest that the virus is (1) an endemic arbordae, (2) transmitted in a continuous cycle throughout the year by Culiseta melanura mosquitoes, and (3) restricted to fresh water swamps and waterways in central, north, and northwest Florida.", "contents": "Occurrence and distribution of western equine encephalomyelitis in Florida. Research and surveillance programs relating to the occurrence and distribution of western equine encephalomyelitis virus in Florida, conducted between 1955 and 1976, suggest that the virus is (1) an endemic arbordae, (2) transmitted in a continuous cycle throughout the year by Culiseta melanura mosquitoes, and (3) restricted to fresh water swamps and waterways in central, north, and northwest Florida."}
{"id": "PMID:23377", "title": "Spectrophotometric determination of strychnine and brucine in liquid galenicals.", "content": "A rapid method is presented for determining strychnine and brucine in liquid galenicals. At pH 5.0, both strychnine and brucine are complexed with methyl orange. After treatment with 0.1N NaOH, the liberated alkaloids are determined spectrophotometrically, using the 2-wavelength method of analysis. The method has been successfully applied to the analysis of 4 batches of nux vomica tincture, nux vomica acid, and nux vomica alkaline mixtures. The method has a relative standard deviation of 0.52%.", "contents": "Spectrophotometric determination of strychnine and brucine in liquid galenicals. A rapid method is presented for determining strychnine and brucine in liquid galenicals. At pH 5.0, both strychnine and brucine are complexed with methyl orange. After treatment with 0.1N NaOH, the liberated alkaloids are determined spectrophotometrically, using the 2-wavelength method of analysis. The method has been successfully applied to the analysis of 4 batches of nux vomica tincture, nux vomica acid, and nux vomica alkaline mixtures. The method has a relative standard deviation of 0.52%."}
{"id": "PMID:23378", "title": "Photooxidation and carbethoxylation of a minor ribonuclease from Aspergillus saitoi.", "content": "In order to investigate the nature of amino acid residues involved in the active in the active site of a ribonuclease from Aspergillus saitoi, the pH dependence of the rates of inactivation of RNase Ms by photooxidation and modification with diethylpyrocarbonate were studied. (1) RNase Ms was inactivated by illumination in the presence of methylene blue at various pH's. The pH dependence of the rate of photooxidative inactivation of RNase Ms indicated that at least one functional group having pKa 7.2 was involved in the active site. (2) Amino acid analyses of photooxidized RNase Ms at various stages of photooxidative inactivation at pH's 4.0 and 6.0 indicated that one histidine residue was related to the activity of RNase Ms, but that no tryptophan residue was involved in the active site. (3) 2',(3')-AMP prevented the photooxidative inactivation of RNase Ms. The results also indicated the presence of a histidine residue in the active site. (4) Modification of RNase Ms with diethylpyrocarbonate was studied at various pH's. The results indicated that a functional group having pKa 7.1 was involved in the active site of RNase Ms.", "contents": "Photooxidation and carbethoxylation of a minor ribonuclease from Aspergillus saitoi. In order to investigate the nature of amino acid residues involved in the active in the active site of a ribonuclease from Aspergillus saitoi, the pH dependence of the rates of inactivation of RNase Ms by photooxidation and modification with diethylpyrocarbonate were studied. (1) RNase Ms was inactivated by illumination in the presence of methylene blue at various pH's. The pH dependence of the rate of photooxidative inactivation of RNase Ms indicated that at least one functional group having pKa 7.2 was involved in the active site. (2) Amino acid analyses of photooxidized RNase Ms at various stages of photooxidative inactivation at pH's 4.0 and 6.0 indicated that one histidine residue was related to the activity of RNase Ms, but that no tryptophan residue was involved in the active site. (3) 2',(3')-AMP prevented the photooxidative inactivation of RNase Ms. The results also indicated the presence of a histidine residue in the active site. (4) Modification of RNase Ms with diethylpyrocarbonate was studied at various pH's. The results indicated that a functional group having pKa 7.1 was involved in the active site of RNase Ms."}
{"id": "PMID:23379", "title": "Formations of electrochemical proton gradient and adenosine triphosphate in proteoliposomes containing purified adenosine triphosphatase and bacteriorhodopsin.", "content": "Proteoliposome vesicles containing both bacteriorhodopsin of Halobacterium halobium and H+-translocating ATPase [EC 3.6,1.3] of a thermophilic bacterium, PS3, (TF0-F1) were reconstituted by either the dialysis method or the sonication method. Generation of the electrochemical proton gradient (deltamuH+) in these vesicles was measured using 9-aminoacridine for estimation of the chemical (deltapH) component and 8-anilinonaphthalene sulfonate for the electrical (deltaphi) component). In illuminated bacteriorhodopsin-vesicles the deltamuH+ reached 180-190 mV when reconstituted by the dialysis method and 210-220 mV when reconstituted by the sonication method. Vesicles reconstituted from both TF0-F1 and bacteriorhodopsin by the dialysis method generated a deltapH+ of about 200 mV on addition of ATP, while vesicles prepared by the sonication method generated very little deltamuH+, if any. These vesicles generated similar deltamuH+ on illumination to that found in bacteriorhodopsin-vesicles. Using vesicles reconstituted from both TF0-F1 and bacteriorhodopsin by the dialysis method, light dependent ATP synthesis was measured in relation to deltamuH+ formation. It was necessary to generate a deltamuH+ of above 170 mV for demonstration of appreciable formation of ATP and the greater the deltamuH+, the faster the rate of ATP synthesis.", "contents": "Formations of electrochemical proton gradient and adenosine triphosphate in proteoliposomes containing purified adenosine triphosphatase and bacteriorhodopsin. Proteoliposome vesicles containing both bacteriorhodopsin of Halobacterium halobium and H+-translocating ATPase [EC 3.6,1.3] of a thermophilic bacterium, PS3, (TF0-F1) were reconstituted by either the dialysis method or the sonication method. Generation of the electrochemical proton gradient (deltamuH+) in these vesicles was measured using 9-aminoacridine for estimation of the chemical (deltapH) component and 8-anilinonaphthalene sulfonate for the electrical (deltaphi) component). In illuminated bacteriorhodopsin-vesicles the deltamuH+ reached 180-190 mV when reconstituted by the dialysis method and 210-220 mV when reconstituted by the sonication method. Vesicles reconstituted from both TF0-F1 and bacteriorhodopsin by the dialysis method generated a deltapH+ of about 200 mV on addition of ATP, while vesicles prepared by the sonication method generated very little deltamuH+, if any. These vesicles generated similar deltamuH+ on illumination to that found in bacteriorhodopsin-vesicles. Using vesicles reconstituted from both TF0-F1 and bacteriorhodopsin by the dialysis method, light dependent ATP synthesis was measured in relation to deltamuH+ formation. It was necessary to generate a deltamuH+ of above 170 mV for demonstration of appreciable formation of ATP and the greater the deltamuH+, the faster the rate of ATP synthesis."}
{"id": "PMID:23384", "title": "Effects of pH and type of sugar in the medium on tyrosinase activity in cultured melanoma cells.", "content": "The tyrosinase (EC 1.14.18.1) activity of cultured mouse melanoma cells B16 in the stationary phase of growth, depends greatly on the pH of the medium and the kind of sugar present. The enzyme activity of a homogenate of cells grown at pH 7.2 in Eagles's MEM supplemented with 10% new born calf serum and con taining galactose in place of glucose, was about ten times that of a homogenate of cells cultured at pH 6.3 in the same medium. The tyrosinase activity changed reversibly on changing the pH of the culture medium. When cultured at a constant pH of 7.2, cells grown with 1 mM galactose had about five times higher tyrosinase activity than cells grown with 1 mM glucose. Only a small amount of lactate accumulated in cultures with glucose and it had little effect on the enzyme activity. These two findings explain the very low tyrosinase activity of cells cultured in medium with 5 mM glucose: the low activity is due to the presence of glucose and to the low pH resulting from conversion of glucose to lactic acid.", "contents": "Effects of pH and type of sugar in the medium on tyrosinase activity in cultured melanoma cells. The tyrosinase (EC 1.14.18.1) activity of cultured mouse melanoma cells B16 in the stationary phase of growth, depends greatly on the pH of the medium and the kind of sugar present. The enzyme activity of a homogenate of cells grown at pH 7.2 in Eagles's MEM supplemented with 10% new born calf serum and con taining galactose in place of glucose, was about ten times that of a homogenate of cells cultured at pH 6.3 in the same medium. The tyrosinase activity changed reversibly on changing the pH of the culture medium. When cultured at a constant pH of 7.2, cells grown with 1 mM galactose had about five times higher tyrosinase activity than cells grown with 1 mM glucose. Only a small amount of lactate accumulated in cultures with glucose and it had little effect on the enzyme activity. These two findings explain the very low tyrosinase activity of cells cultured in medium with 5 mM glucose: the low activity is due to the presence of glucose and to the low pH resulting from conversion of glucose to lactic acid."}
{"id": "PMID:23385", "title": "Toxicity, radiation sensitivity modification, and metabolic effects of dehydroascorbate and ascorbate in mammalian cells.", "content": "Dehydroascorbate, an electron affinic metabolite of vitamin C, sensitized Ehrlich ascites tumor cells, in vivo, to radiation and was selectively toxic to V79 Chinese hamster lung cells under hypoxic conditions (without radiation). The radiosensitization may involve both the electron affinic nature of dehydroascorbate as well as its ability to oxidize the intracellular NAD(P)H and non-protein sulfhydryl. Dehydroascorbate's oxidation of NAD(P)H required higher concentrations than other sulfhydryl oxidants such as N-ethylmaleimide and diamide. The oxidation of NAD(P)H by dehydroascorbate could be reversed by glucose. Hypoxic cell radiosensitization of V79 cells in tissue culture by dehydroascorbate could not be easily demonstrated because of the rapid breakdown and appreciable cytotoxicity of the drug at high concentration. The cytotoxicity was found to occur with both high and low densities of V79 cells. With low cell densities small amounts of oxygen did not reduce the cytotoxicity of dehydroascorbate, but virtually eliminated the cytotoxicity of nitroaromatic electron affinic compounds (metronidazole and Ro-07-0582). The cytotoxicity to dense cell suspensions was found to depend upon the type of buffer included in the reaction medium. The maximum cytotoxicity was obtained in buffer free saline. The reduced form of dehydroascorbate, vitamin C, was found to be toxic only under aerobic conditions. The aerobic cytotoxicity could be prevented by the addition of catalase to the growth medium or by an increase in cell density, suggesting it was caused entirely by the production of H2O2 from the oxidation of vitamin C.", "contents": "Toxicity, radiation sensitivity modification, and metabolic effects of dehydroascorbate and ascorbate in mammalian cells. Dehydroascorbate, an electron affinic metabolite of vitamin C, sensitized Ehrlich ascites tumor cells, in vivo, to radiation and was selectively toxic to V79 Chinese hamster lung cells under hypoxic conditions (without radiation). The radiosensitization may involve both the electron affinic nature of dehydroascorbate as well as its ability to oxidize the intracellular NAD(P)H and non-protein sulfhydryl. Dehydroascorbate's oxidation of NAD(P)H required higher concentrations than other sulfhydryl oxidants such as N-ethylmaleimide and diamide. The oxidation of NAD(P)H by dehydroascorbate could be reversed by glucose. Hypoxic cell radiosensitization of V79 cells in tissue culture by dehydroascorbate could not be easily demonstrated because of the rapid breakdown and appreciable cytotoxicity of the drug at high concentration. The cytotoxicity was found to occur with both high and low densities of V79 cells. With low cell densities small amounts of oxygen did not reduce the cytotoxicity of dehydroascorbate, but virtually eliminated the cytotoxicity of nitroaromatic electron affinic compounds (metronidazole and Ro-07-0582). The cytotoxicity to dense cell suspensions was found to depend upon the type of buffer included in the reaction medium. The maximum cytotoxicity was obtained in buffer free saline. The reduced form of dehydroascorbate, vitamin C, was found to be toxic only under aerobic conditions. The aerobic cytotoxicity could be prevented by the addition of catalase to the growth medium or by an increase in cell density, suggesting it was caused entirely by the production of H2O2 from the oxidation of vitamin C."}
{"id": "PMID:23386", "title": "Phenylalanine hydroxylase in melanoma cells.", "content": "A pigmented subclone of Cloudman S91 melanoma cells, PS1-wild type, can grow in medium lacking tyrosine. This ability is conferred by phenylalanine hydroxylase activity, and not by tryptophan hydroxylase, tyrosine hydroxylase or tyrosinase activities, although the latter activity is also present in these cells. Conversion of phenylalanine to tyrosine was measured in living cells by chromatographic identification of the metabolites of [14C]phenylalanine and in cell extracts using a sensitive assay for phenylalanine hydroxylase. Phenylalanine hydroxylase activity in melanoma cell extracts was identified by its inhibition with p-chlorophenylalanine and not with 6-fluorotryptophan, 3-iodotyrosine, phenylthiourea, tyrosine or tryptophan; and by adsorption with antiserum prepared against purified rat liver phenylalanine hydroxylase, and migration of immunoprecipitable activity with authentic phenylalanine hydroxylase subunits in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.", "contents": "Phenylalanine hydroxylase in melanoma cells. A pigmented subclone of Cloudman S91 melanoma cells, PS1-wild type, can grow in medium lacking tyrosine. This ability is conferred by phenylalanine hydroxylase activity, and not by tryptophan hydroxylase, tyrosine hydroxylase or tyrosinase activities, although the latter activity is also present in these cells. Conversion of phenylalanine to tyrosine was measured in living cells by chromatographic identification of the metabolites of [14C]phenylalanine and in cell extracts using a sensitive assay for phenylalanine hydroxylase. Phenylalanine hydroxylase activity in melanoma cell extracts was identified by its inhibition with p-chlorophenylalanine and not with 6-fluorotryptophan, 3-iodotyrosine, phenylthiourea, tyrosine or tryptophan; and by adsorption with antiserum prepared against purified rat liver phenylalanine hydroxylase, and migration of immunoprecipitable activity with authentic phenylalanine hydroxylase subunits in sodium dodecyl sulfate-polyacrylamide gel electrophoresis."}
{"id": "PMID:23388", "title": "Determination of water soluble imidazo-1,4-benzodiazepines in blood by electron- capture gas--liquid chromatography and in urine by differential pulse polaragraphy.", "content": "A sensitive and specific electron-capture gas--liquid chromatographic (GLC--ECD) assay was developed for the determination of 8-chloro-6-(2'-fluorophenyl)-1-methyl-4H-imidazo(1,5a)(1,4)benzodiazepine (I) or 8-chloro-1,4-dimethyl-6-(2'-fluorophenyl)-4H-imidazo (1,5a)(1,4)benzodiazepine (II) in blood. The assay for both compounds involves extraction into benzene--methylene chloride (9:1) from blood buffered to pH 12.6 The overall recovery of I and II from blood is 86% +- 5.0 (S.D.) and the sensitivity limit of detection is of the order of 2 to 3 ng of I or II per milliltre of blood. The major urinary metabolite of I is 8-chloro-6-(2'-fluorophenyl)-1-hydroxymethyl-4H-imidazo(1,5a)(1,4)benzodiazepine, (IA) present as a glucuronide conjugate while 8-chloro-6-(2'-fluorophenyl)-4-hydroxyl-1-methyl-4H-imidazo(1,5a)(1,4)benzodiazepine, (IB) and 8-chloro-6-(2'-fluorophenyl)-4-hydroxy-1-hydroxymethyl-4H-imidazo(1,5a)(1,4) benzodiazepine, (IC) are minor metabolites. The major metabolite IA is extracted into benzene--methylene chloride (9:1) from urine buffered to pH 11.0 (after incubation with glucuronidase--sulfatase as pH 5.0), and analyzed by differential pulse polarography (DPP) in 0.1 M phosphate buffer PH 3). The overall recovery of IA is 84 +- 3.0% (S.D.) with a sensitivity limit of 50 ng per millilitre of urine. The metabolites of compound II have not as yet been elucidated. The GLC--ECD and DPP assays were applied to the determination of blood levels and urinary excretion in dogs following single 10 mg/kg intravenous and oral doses of I and following single 6 mg/kg intravenous and 10 mg/kg oral doses of II. Blood levels of compound I were also evaluated in man following intravenous infusion of single 10 mg doses.", "contents": "Determination of water soluble imidazo-1,4-benzodiazepines in blood by electron- capture gas--liquid chromatography and in urine by differential pulse polaragraphy. A sensitive and specific electron-capture gas--liquid chromatographic (GLC--ECD) assay was developed for the determination of 8-chloro-6-(2'-fluorophenyl)-1-methyl-4H-imidazo(1,5a)(1,4)benzodiazepine (I) or 8-chloro-1,4-dimethyl-6-(2'-fluorophenyl)-4H-imidazo (1,5a)(1,4)benzodiazepine (II) in blood. The assay for both compounds involves extraction into benzene--methylene chloride (9:1) from blood buffered to pH 12.6 The overall recovery of I and II from blood is 86% +- 5.0 (S.D.) and the sensitivity limit of detection is of the order of 2 to 3 ng of I or II per milliltre of blood. The major urinary metabolite of I is 8-chloro-6-(2'-fluorophenyl)-1-hydroxymethyl-4H-imidazo(1,5a)(1,4)benzodiazepine, (IA) present as a glucuronide conjugate while 8-chloro-6-(2'-fluorophenyl)-4-hydroxyl-1-methyl-4H-imidazo(1,5a)(1,4)benzodiazepine, (IB) and 8-chloro-6-(2'-fluorophenyl)-4-hydroxy-1-hydroxymethyl-4H-imidazo(1,5a)(1,4) benzodiazepine, (IC) are minor metabolites. The major metabolite IA is extracted into benzene--methylene chloride (9:1) from urine buffered to pH 11.0 (after incubation with glucuronidase--sulfatase as pH 5.0), and analyzed by differential pulse polarography (DPP) in 0.1 M phosphate buffer PH 3). The overall recovery of IA is 84 +- 3.0% (S.D.) with a sensitivity limit of 50 ng per millilitre of urine. The metabolites of compound II have not as yet been elucidated. The GLC--ECD and DPP assays were applied to the determination of blood levels and urinary excretion in dogs following single 10 mg/kg intravenous and oral doses of I and following single 6 mg/kg intravenous and 10 mg/kg oral doses of II. Blood levels of compound I were also evaluated in man following intravenous infusion of single 10 mg doses."}
{"id": "PMID:23390", "title": "Determination of the metabolites of bezitramide in urine. I. Acidic metabolite.", "content": "Two methylation methods are compared in relation to the determination of low levels (less than microgram/ml) of the acidic metabolite of bezitramide in human urine. It was necessary to use alkali flame ionisation detector, which specifically detects nitrogen-containing compounds. Several difficulties associated with the use of this detector are described.", "contents": "Determination of the metabolites of bezitramide in urine. I. Acidic metabolite. Two methylation methods are compared in relation to the determination of low levels (less than microgram/ml) of the acidic metabolite of bezitramide in human urine. It was necessary to use alkali flame ionisation detector, which specifically detects nitrogen-containing compounds. Several difficulties associated with the use of this detector are described."}
{"id": "PMID:23391", "title": "Electron spin resonance studies of erythrocytes from patients with Duchenne muscular dystrophy.", "content": "The membrane organization of the erythrocytes from patients with Duchenne muscular dystrophy was studied by means of electron spin resonance. The fluidity of the membrane near the polar region of Duchenne muscular dystrophy erythrocytes was similar to that of normal erythrocytes. The membrane environment in the nonpolar region, however, was quite different from that of normal erythrocytes, judged by the spectra with 2-(14-carboxytetradecyl) - 2 - ethyl - 4,4 - dimethyl - 3 - oxazolidinyloxyl as probe. The temperature dependence of the ratio of the line height of central field to that at the low field showed two inflection points in normal erythrocytes at pH 7.4 (13.5 degrees -16.5 degrees and 37.5 degrees -40.5 degrees C, respectively) but the inflection point in the lower temperature range was not detected in Duchenne muscular dystrophy erythrocytes. When pH was varied, an abrupt decrease in the ratio was observed at pH 5.9-5.6 in normal erythrocytes whereas there was a gradual decrease over the range of pH from 6.6 to 5.0 in Duchenne muscular dystrophy erythrocytes. The rate of reduction of the radical 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl by ascorbate in normal erythrocytes was faster than that in Duchenne muscular dystrophy erythrocytes. Treatment of both erythrocytes with phloretin markedly reduced the rate of reduction by ascorbate and eliminated the difference in the two types of erythrocyte. These results indicate that in Duchenne muscular dystrophy the erythrocyte membrane is involved as well as the muscle cell.", "contents": "Electron spin resonance studies of erythrocytes from patients with Duchenne muscular dystrophy. The membrane organization of the erythrocytes from patients with Duchenne muscular dystrophy was studied by means of electron spin resonance. The fluidity of the membrane near the polar region of Duchenne muscular dystrophy erythrocytes was similar to that of normal erythrocytes. The membrane environment in the nonpolar region, however, was quite different from that of normal erythrocytes, judged by the spectra with 2-(14-carboxytetradecyl) - 2 - ethyl - 4,4 - dimethyl - 3 - oxazolidinyloxyl as probe. The temperature dependence of the ratio of the line height of central field to that at the low field showed two inflection points in normal erythrocytes at pH 7.4 (13.5 degrees -16.5 degrees and 37.5 degrees -40.5 degrees C, respectively) but the inflection point in the lower temperature range was not detected in Duchenne muscular dystrophy erythrocytes. When pH was varied, an abrupt decrease in the ratio was observed at pH 5.9-5.6 in normal erythrocytes whereas there was a gradual decrease over the range of pH from 6.6 to 5.0 in Duchenne muscular dystrophy erythrocytes. The rate of reduction of the radical 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl by ascorbate in normal erythrocytes was faster than that in Duchenne muscular dystrophy erythrocytes. Treatment of both erythrocytes with phloretin markedly reduced the rate of reduction by ascorbate and eliminated the difference in the two types of erythrocyte. These results indicate that in Duchenne muscular dystrophy the erythrocyte membrane is involved as well as the muscle cell."}
{"id": "PMID:23392", "title": "Identification of alpha-adrenergic receptors in human platelets by [3H]dihydroergocryptine binding.", "content": "Binding of [(3)H]dihydroergocryptine to platelet lysates appears to have all the characteristics of binding to alpha-adrenergic receptors. At 25 degrees C binding reaches equilibrium within 20 min and is reversible upon addition of excess phentolamine. Binding is saturable with 183+/-22 fmol of [(3)H]dihydroergocryptine bound per mg of protein at saturation, corresponding to 220+/-26 sites per platelet. Kinetic and equilibrium studies indicate the dissociation constant of [(3)H]dihydroergocryptine for the receptors is 1-3 nM. The specificity of the binding sites is typical of an alpha-adrenergic receptor. Catecholamine agonists compete for occupancy of the [(3)H]dihydroergocryptine binding sites with an order of potency (-)epinephrine> (-)norepinephrine>> (-)isoproterenol. Stereospecificity was demonstrated inasmuch as the (+)isomers of epinephrine and norepinephrine were 10-20-fold less potent than the (-)isomers. The potent alpha-adrenergic antagonists phentolamine, phenoxybenzamine, and yohimbine competed potently for the sites, whereas beta-antagonists such as propranolol and dichlorisoproterenol were quite weak. Dopamine and serotonin competed only at high concentrations (0.1 mM). The [(3)H]dihydroergocryptine binding sites could also be demonstrated in intact platelets where they displayed comparable specificity, stereospecificity, and saturability. Saturation binding studies with the intact platelets indicated 220+/-45 receptors per platelet, in good agreement with the value derived from studies with platelet lysates. Ability of alpha-adrenergic agonists to inhibit adenylate cyclase and of alpha-adrenergic antagonists to antagonize this inhibitory effect directly paralleled ability to interact with the [(3)H]dihydroergocryptine binding sites. These data demonstrate the feasibility of directly studying alpha-adrenergic receptor binding sites in human platelets with [(3)H]dihydroergocryptine.", "contents": "Identification of alpha-adrenergic receptors in human platelets by [3H]dihydroergocryptine binding. Binding of [(3)H]dihydroergocryptine to platelet lysates appears to have all the characteristics of binding to alpha-adrenergic receptors. At 25 degrees C binding reaches equilibrium within 20 min and is reversible upon addition of excess phentolamine. Binding is saturable with 183+/-22 fmol of [(3)H]dihydroergocryptine bound per mg of protein at saturation, corresponding to 220+/-26 sites per platelet. Kinetic and equilibrium studies indicate the dissociation constant of [(3)H]dihydroergocryptine for the receptors is 1-3 nM. The specificity of the binding sites is typical of an alpha-adrenergic receptor. Catecholamine agonists compete for occupancy of the [(3)H]dihydroergocryptine binding sites with an order of potency (-)epinephrine> (-)norepinephrine>> (-)isoproterenol. Stereospecificity was demonstrated inasmuch as the (+)isomers of epinephrine and norepinephrine were 10-20-fold less potent than the (-)isomers. The potent alpha-adrenergic antagonists phentolamine, phenoxybenzamine, and yohimbine competed potently for the sites, whereas beta-antagonists such as propranolol and dichlorisoproterenol were quite weak. Dopamine and serotonin competed only at high concentrations (0.1 mM). The [(3)H]dihydroergocryptine binding sites could also be demonstrated in intact platelets where they displayed comparable specificity, stereospecificity, and saturability. Saturation binding studies with the intact platelets indicated 220+/-45 receptors per platelet, in good agreement with the value derived from studies with platelet lysates. Ability of alpha-adrenergic agonists to inhibit adenylate cyclase and of alpha-adrenergic antagonists to antagonize this inhibitory effect directly paralleled ability to interact with the [(3)H]dihydroergocryptine binding sites. These data demonstrate the feasibility of directly studying alpha-adrenergic receptor binding sites in human platelets with [(3)H]dihydroergocryptine."}
{"id": "PMID:23398", "title": "The two dimensional structure of tetrazolium-mucopolysaccharide complexes deduced from reactivity studies.", "content": "The formation of complexes between mucopolysaccharides and tetrazolium salts has been studied both by turbidimetry and nephelometry. The technique of laser nephelometry allows the detection of colloidal aggregates in systems which may, by turbidimetric methods, be ambiguous. The results indicate that binding of tetrazolium salts to polyanions can result in soluble as well as insoluble complexes; the monotetrazolium salts form soluble complexes and the ditetrazolium compounds form insoluble complexes. The insoluble complexes are stable at relatively low pH, and are disrupted during reduction to the formazan. Complex formation is decreased at high ratios of heparin to tetrazolium, and divalent cations, even at high concentration, do not precipitate mucopolysaccharides. It is concluded that stable ionic interactions with spatial charge separation are responsible for the cross linking of the mucopolysaccharides and the formaiton of large insoluble aggregates.", "contents": "The two dimensional structure of tetrazolium-mucopolysaccharide complexes deduced from reactivity studies. The formation of complexes between mucopolysaccharides and tetrazolium salts has been studied both by turbidimetry and nephelometry. The technique of laser nephelometry allows the detection of colloidal aggregates in systems which may, by turbidimetric methods, be ambiguous. The results indicate that binding of tetrazolium salts to polyanions can result in soluble as well as insoluble complexes; the monotetrazolium salts form soluble complexes and the ditetrazolium compounds form insoluble complexes. The insoluble complexes are stable at relatively low pH, and are disrupted during reduction to the formazan. Complex formation is decreased at high ratios of heparin to tetrazolium, and divalent cations, even at high concentration, do not precipitate mucopolysaccharides. It is concluded that stable ionic interactions with spatial charge separation are responsible for the cross linking of the mucopolysaccharides and the formaiton of large insoluble aggregates."}
{"id": "PMID:23399", "title": "Fractionation of cocksfoot (Dactylis glomerata) pollen by preparative isoelectric focussing.", "content": "The technique of isoelectric focussing in polyacrylamide gel has been developed to a preparative mode. Using the improved technique cocksfoot (Dactylis glomerata) pollen has been split into many components, and the allergenic reactions of the preparations have been studied by passive transfer in animal skin and by RAST.", "contents": "Fractionation of cocksfoot (Dactylis glomerata) pollen by preparative isoelectric focussing. The technique of isoelectric focussing in polyacrylamide gel has been developed to a preparative mode. Using the improved technique cocksfoot (Dactylis glomerata) pollen has been split into many components, and the allergenic reactions of the preparations have been studied by passive transfer in animal skin and by RAST."}
{"id": "PMID:23401", "title": "Oxygen uptake and lung function in mice infected with Streptococcus pneumoniae, influenza virus, or Mycoplasma pulmonis.", "content": "Model systems of respiratory infection in mice were established with Streptococcus pneumoniae, influenza virus, and Mycoplasma pulmonis. The LT50 for S. pneumoniae was 2 1/2 days, for lethal influenza 6 days, and for M. pulmonis 5 days. Morbidity in sublethal influenza infections reached a peak during days 5 to 10, with recovery indicated by the third week. The course of each pulmonary infection was followed by use of the animal's maximal ability to consume oxygen (VO2max by determining the weight, compliance, and stability of the excised lung, and in some cases by following O2 consumption of minced tissue. Depression of VO2max began early in each infection; reductions ranged from 9% at the peak of sublethal influenza infection to 50% 12 to 48 hr before the LT50 of fatal infections. The depressions were not relieved by 100% O2. The noninvasive VO2max test, evoked by cold air, was simple, rapid, and reproducible and appeared to serve as a quantitative measure of over-all function during infection. Each type of infection caused an increase in lung weight, with the largest noted during fatal Mycoplasma illness and lethal influenza. The effects on lungs by influenza and M. pulmonis infections were similar but could be differentiated from those with S. pneumoniae. With sublethal influenza, CL was reduced 30% between days 5 to 10, with recovery by the third week. Ctis was not affected. M. pulmonis infections and lethal influenza caused depressions in CL of over 60% by day 4 but only a 30% decrease in Ctis. The data suggest that the decreased compliance in influenza and M. pulmonis infections was due primarily to increased surface tension. In contrast, S. pneumoniae did not affect compliance.", "contents": "Oxygen uptake and lung function in mice infected with Streptococcus pneumoniae, influenza virus, or Mycoplasma pulmonis. Model systems of respiratory infection in mice were established with Streptococcus pneumoniae, influenza virus, and Mycoplasma pulmonis. The LT50 for S. pneumoniae was 2 1/2 days, for lethal influenza 6 days, and for M. pulmonis 5 days. Morbidity in sublethal influenza infections reached a peak during days 5 to 10, with recovery indicated by the third week. The course of each pulmonary infection was followed by use of the animal's maximal ability to consume oxygen (VO2max by determining the weight, compliance, and stability of the excised lung, and in some cases by following O2 consumption of minced tissue. Depression of VO2max began early in each infection; reductions ranged from 9% at the peak of sublethal influenza infection to 50% 12 to 48 hr before the LT50 of fatal infections. The depressions were not relieved by 100% O2. The noninvasive VO2max test, evoked by cold air, was simple, rapid, and reproducible and appeared to serve as a quantitative measure of over-all function during infection. Each type of infection caused an increase in lung weight, with the largest noted during fatal Mycoplasma illness and lethal influenza. The effects on lungs by influenza and M. pulmonis infections were similar but could be differentiated from those with S. pneumoniae. With sublethal influenza, CL was reduced 30% between days 5 to 10, with recovery by the third week. Ctis was not affected. M. pulmonis infections and lethal influenza caused depressions in CL of over 60% by day 4 but only a 30% decrease in Ctis. The data suggest that the decreased compliance in influenza and M. pulmonis infections was due primarily to increased surface tension. In contrast, S. pneumoniae did not affect compliance."}
{"id": "PMID:23402", "title": "Glucose 6-phosphate dehydrogenase variants: Gd (+) Alexandra associated with neonatal jaundice and Gd (-) Camperdown in a young man with lamellar cataracts.", "content": "Two male subjects are described, with unusual clinical presentations and with hitherto undescribed G6PD variants. The first, of Italian extraction, suffered from severe neonatal jaundice following maternal ingestion of fresh broad beans (Vicia fava) both prenatally and postnatally: the expression of the enzymatic defect was much more severe in the neonatal period than on retesting in adolescence, when biochemical characterization showed unique features which justify designation as a new variant Gd(+) Alexandra. The second patient, a boy of Maltese extraction who was found to have bilateral lamellar cataracts at the age of 4 years, was identified as G6PD deficient only as a result of a survey of children of Mediterranean origin with unexplained cataract formation; he has approximately 15% of normal enzyme activity, with another unique combination of biochemical characteristics which has led to its designation as Gd(-) Camperdown. Although this association may be coincidental, it prompts further attention to the possibility that under certain circumstances G6PD deficiency may favor cataract formation. The two cases illustrate the value of characterization of the mutant enzyme whenever unexpected clinical or laboratory results are obtained.", "contents": "Glucose 6-phosphate dehydrogenase variants: Gd (+) Alexandra associated with neonatal jaundice and Gd (-) Camperdown in a young man with lamellar cataracts. Two male subjects are described, with unusual clinical presentations and with hitherto undescribed G6PD variants. The first, of Italian extraction, suffered from severe neonatal jaundice following maternal ingestion of fresh broad beans (Vicia fava) both prenatally and postnatally: the expression of the enzymatic defect was much more severe in the neonatal period than on retesting in adolescence, when biochemical characterization showed unique features which justify designation as a new variant Gd(+) Alexandra. The second patient, a boy of Maltese extraction who was found to have bilateral lamellar cataracts at the age of 4 years, was identified as G6PD deficient only as a result of a survey of children of Mediterranean origin with unexplained cataract formation; he has approximately 15% of normal enzyme activity, with another unique combination of biochemical characteristics which has led to its designation as Gd(-) Camperdown. Although this association may be coincidental, it prompts further attention to the possibility that under certain circumstances G6PD deficiency may favor cataract formation. The two cases illustrate the value of characterization of the mutant enzyme whenever unexpected clinical or laboratory results are obtained."}
{"id": "PMID:23403", "title": "Isolation and characterization of a phospholipase A2 from an inflammatory exudate.", "content": "Sterile peritoneal exudates produced in rabbits injected with 1% glycogen contain a phospholipase A activity in a cell-free supernatant fraction that hydrolyzed a synthetic phospholipid (1,2-diacyl-sn-glycero-3-phospho-ethanolamine) and phospholipids of autoclaved Escherichia coli. This phospholipase activity (phosphatidylacylhydrolase EC 3.1.1.4) exhibited an apparent bimodal pH optimum (pH 6.0 and pH 7.5) and was Ca(2+)-dependent; Mg(2+) and monovalent cations (Na(+) and K(+)) did not substitute for Ca(2+) in the reaction; EDTA was a potent inhibitor. The phospholipase hydrolyzed 1-[1-(14)C]palmitoyl-2-acyl-sn-glycero-3-phosphoethanolamine to form only radio-active lysophosphatidylethanolamine as the product, indicating that the enzyme had phospholipase A(2) specificity. The phospholipase A(2) was purified 302-fold by two successive chromatographic steps on carboxymethyl Sephadex. Gel filtration (Sephadex G75) of the purified enzyme resulted in a single peak of biological activity with a molecular weight of approximately 14,800. The same estimate of molecular weight was obtained by SDS-polyacrylamide gel electrophoresis, which yielded a single band. Polyacrylamide gel electrophoresis of this fraction at pH 4.3 revealed a single protein band migrating beyond lysozyme, with the dye front, suggesting that this protein was more basic than lysozyme (pI 10.5). The enzymatic and physical-chemical characteristics of this soluble enzyme were remarkably similar to a recently described phospholipase A(2) of rabbit polymorphonuclear leukocytes derived from glycogen-induced peritoneal exudates. The possible origin and physiological role of this soluble enzyme are discussed.", "contents": "Isolation and characterization of a phospholipase A2 from an inflammatory exudate. Sterile peritoneal exudates produced in rabbits injected with 1% glycogen contain a phospholipase A activity in a cell-free supernatant fraction that hydrolyzed a synthetic phospholipid (1,2-diacyl-sn-glycero-3-phospho-ethanolamine) and phospholipids of autoclaved Escherichia coli. This phospholipase activity (phosphatidylacylhydrolase EC 3.1.1.4) exhibited an apparent bimodal pH optimum (pH 6.0 and pH 7.5) and was Ca(2+)-dependent; Mg(2+) and monovalent cations (Na(+) and K(+)) did not substitute for Ca(2+) in the reaction; EDTA was a potent inhibitor. The phospholipase hydrolyzed 1-[1-(14)C]palmitoyl-2-acyl-sn-glycero-3-phosphoethanolamine to form only radio-active lysophosphatidylethanolamine as the product, indicating that the enzyme had phospholipase A(2) specificity. The phospholipase A(2) was purified 302-fold by two successive chromatographic steps on carboxymethyl Sephadex. Gel filtration (Sephadex G75) of the purified enzyme resulted in a single peak of biological activity with a molecular weight of approximately 14,800. The same estimate of molecular weight was obtained by SDS-polyacrylamide gel electrophoresis, which yielded a single band. Polyacrylamide gel electrophoresis of this fraction at pH 4.3 revealed a single protein band migrating beyond lysozyme, with the dye front, suggesting that this protein was more basic than lysozyme (pI 10.5). The enzymatic and physical-chemical characteristics of this soluble enzyme were remarkably similar to a recently described phospholipase A(2) of rabbit polymorphonuclear leukocytes derived from glycogen-induced peritoneal exudates. The possible origin and physiological role of this soluble enzyme are discussed."}
{"id": "PMID:23404", "title": "CO2-inhibition of the amplitude of bending of triton-demembranated sea urcin sperm flagella.", "content": "Demembranated sea urchin spermatozoa were reactivated in solutions containing KHCO3 and observed in a covered well slide. Although KHCO3 itself causes a small inhibition of flagellar beat frequency, the results confirm previous observations of a direct inhibition of flagellar bend angle by CO2 with no effect of CO2 on frequency. Observation of the effect of pH on the inhibition of bend angle in solutions containing KHCO3 indicates that a given concentration of OH- has a similar effect to the same concentration of HCO3-, as would be expected if CO2- inhibition results from reaction of CO2 with protein-NH3+ groups to form carbamates. CO2 may interfere with a control mechanism which selectively suppresses dynein cross-bridge activity in order to generate rhythmic bending. This control mechanism may incorporate a feedback control involving a measure of flagellar amplitude, which fails to operate successfully when the amplitude is reduced below a critical level.", "contents": "CO2-inhibition of the amplitude of bending of triton-demembranated sea urcin sperm flagella. Demembranated sea urchin spermatozoa were reactivated in solutions containing KHCO3 and observed in a covered well slide. Although KHCO3 itself causes a small inhibition of flagellar beat frequency, the results confirm previous observations of a direct inhibition of flagellar bend angle by CO2 with no effect of CO2 on frequency. Observation of the effect of pH on the inhibition of bend angle in solutions containing KHCO3 indicates that a given concentration of OH- has a similar effect to the same concentration of HCO3-, as would be expected if CO2- inhibition results from reaction of CO2 with protein-NH3+ groups to form carbamates. CO2 may interfere with a control mechanism which selectively suppresses dynein cross-bridge activity in order to generate rhythmic bending. This control mechanism may incorporate a feedback control involving a measure of flagellar amplitude, which fails to operate successfully when the amplitude is reduced below a critical level."}
{"id": "PMID:23405", "title": "Differences in the outcomes of acute episodes of care provided by various types of family practitioners.", "content": "This study was designed to compare the outcomes achieved in a series of acute care episodes by different levels of family practice providers working in the clinic setting. The study utilizes a method which depends upon the provider to estimate level of function expected and earliest date of recovery for each episode. When the patients are viewed as a single group, those patients treated by the medex appear to fare considerably better and those seen by a faculty member do worse; however, when each functional status group is examined separately, only the asymptomatic but clinically ill patients (45 cases) show a statistically significant difference in outcomes among the providers, with the medex having good results and the faculty poor results.", "contents": "Differences in the outcomes of acute episodes of care provided by various types of family practitioners. This study was designed to compare the outcomes achieved in a series of acute care episodes by different levels of family practice providers working in the clinic setting. The study utilizes a method which depends upon the provider to estimate level of function expected and earliest date of recovery for each episode. When the patients are viewed as a single group, those patients treated by the medex appear to fare considerably better and those seen by a faculty member do worse; however, when each functional status group is examined separately, only the asymptomatic but clinically ill patients (45 cases) show a statistically significant difference in outcomes among the providers, with the medex having good results and the faculty poor results."}
{"id": "PMID:23406", "title": "Sodium and calcium movements in dog red blood cells.", "content": "Determinants of 45Ca influx, 45Ca efflux, and 22Na efflux were examined in dog red blood cells. 45Ca influx is strongly influenced by the Na concentration on either side of the membrane, being stimulated by intracellular Na and inhibited by extracellular Na. A saturation curve is obtained when Ca influx is plotted as a function of medium Ca concentration. The maximum Ca influx is a function of pH (increasing with greater alkalinity) and cell volume (increasing with cell swelling). Quinidine strongly inhibits Ca influx. Efflux of 45Ca is stimulated by increasing concentrations of extracellular Na. 22Na efflux is stimulated by either Ca or Na in the medium, and the effects of the two ions are mutually exclusive rather than additive. Quinidine inhibits Ca-activated 22Na efflux. The results are considered in terms of a model for Ca-Na exchange, and it is concluded that the system shows many features of such a coupled ion transport system. However, the stoichiometric ratio between Ca influx and Ca-dependent Na efflux is highly variable under different experimental conditions. Because the Ca fluxes may reflect a combination of ATP-dependent, outward transport and Na-linked passive movements, the true stoichiometry of an exchanger may not be ascertainable in the absence of a specific Ca pump inhibitor. The meaning of these observations for Ca-dependent volume regulation by dog red blood cells is discussed.", "contents": "Sodium and calcium movements in dog red blood cells. Determinants of 45Ca influx, 45Ca efflux, and 22Na efflux were examined in dog red blood cells. 45Ca influx is strongly influenced by the Na concentration on either side of the membrane, being stimulated by intracellular Na and inhibited by extracellular Na. A saturation curve is obtained when Ca influx is plotted as a function of medium Ca concentration. The maximum Ca influx is a function of pH (increasing with greater alkalinity) and cell volume (increasing with cell swelling). Quinidine strongly inhibits Ca influx. Efflux of 45Ca is stimulated by increasing concentrations of extracellular Na. 22Na efflux is stimulated by either Ca or Na in the medium, and the effects of the two ions are mutually exclusive rather than additive. Quinidine inhibits Ca-activated 22Na efflux. The results are considered in terms of a model for Ca-Na exchange, and it is concluded that the system shows many features of such a coupled ion transport system. However, the stoichiometric ratio between Ca influx and Ca-dependent Na efflux is highly variable under different experimental conditions. Because the Ca fluxes may reflect a combination of ATP-dependent, outward transport and Na-linked passive movements, the true stoichiometry of an exchanger may not be ascertainable in the absence of a specific Ca pump inhibitor. The meaning of these observations for Ca-dependent volume regulation by dog red blood cells is discussed."}
{"id": "PMID:23407", "title": "The stimulating effect of fatty acids and amino acid derivatives on the labellar sugar receptor of the fleshfly.", "content": "Seven D-amino acids, including D-valine, D-phenylalanine, D-leucine, D-isoleucine, D-tryptophan, D-methionine, and D-alpha-aminobutyric acid, are markedly less stimulative than the corresponding L-isomers that can stimulate the labellar sugar receptor of the fleshfly. A distinct effect of len;th of the amino acid side chain is clearly observed. Esterification and amidation of the alpha-carboxyl group, as well as substitution by hydroxyl and methyl groups, result in extremely decreased responses. Amino acids whose amino groups are located at a position other than the alpha are almost ineffective. With all these rigid stereospecificities of the sugar receptor for amino acids, certain replacement of the alpha-amino group with the hydroxyl or carbonyl group shows a slight increase of the response at neutral pH. Furthermore, certain fatty acids can stimulate the sugar receptor once the solutions are buffered at neutral pH. This observation was further supported by the presence of a remarkable similarity of stimulating effectiveness between amino acids that can stimulate the sugar receptor and those fatty acids. The similarity was shown by testing the response concentration relationships, the stimulating effect of fatty acid derivatives, the effect of treatment with p-chloromercuribenzoate, the behavioral response, and so on.", "contents": "The stimulating effect of fatty acids and amino acid derivatives on the labellar sugar receptor of the fleshfly. Seven D-amino acids, including D-valine, D-phenylalanine, D-leucine, D-isoleucine, D-tryptophan, D-methionine, and D-alpha-aminobutyric acid, are markedly less stimulative than the corresponding L-isomers that can stimulate the labellar sugar receptor of the fleshfly. A distinct effect of len;th of the amino acid side chain is clearly observed. Esterification and amidation of the alpha-carboxyl group, as well as substitution by hydroxyl and methyl groups, result in extremely decreased responses. Amino acids whose amino groups are located at a position other than the alpha are almost ineffective. With all these rigid stereospecificities of the sugar receptor for amino acids, certain replacement of the alpha-amino group with the hydroxyl or carbonyl group shows a slight increase of the response at neutral pH. Furthermore, certain fatty acids can stimulate the sugar receptor once the solutions are buffered at neutral pH. This observation was further supported by the presence of a remarkable similarity of stimulating effectiveness between amino acids that can stimulate the sugar receptor and those fatty acids. The similarity was shown by testing the response concentration relationships, the stimulating effect of fatty acid derivatives, the effect of treatment with p-chloromercuribenzoate, the behavioral response, and so on."}
{"id": "PMID:23408", "title": "On the effects of divalent cations and ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetate on action potential duration in frog heart.", "content": "Resting and action potentials were recorded from superfused strips of frog ventricle. Reducing the bathing calcium concentration ([Ca2+]0) with or without ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA) prolongs the action potential (AP). The change in the duration of the AP extends over many minutes, but is rapidly reversed by restoring calcium ions. Other changes (e.g., in resting potential and overshoot) are, however, only more slowly reversed. Reducing [Ca2+]0 with 0.2, 2, or 5 mM EGTA produces progressively greater prolongation of AP; maximum values were well in excess of 1 min. This prolongation can be reversed by other divalent cations in EGTA (Mg2+, Sr2+) or Ca-free (Mn2+) solutions, or by acetylcholine. Barium ions increase AP duration in keeping with their known effect on potassium conductance. D600, which blocks the slow inward current in cardiac muscle, is without effect on the action potentials recorded in EGTA solutions, or on the time course and extent of the recovery to normal duration upon restoring calcium ions. It is concluded that divalent cations exert an influence on membrane potassium conductance extracellularly in frog heart. The cell membrane does not become excessively \"leaky\" in EGTA solutions.", "contents": "On the effects of divalent cations and ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetate on action potential duration in frog heart. Resting and action potentials were recorded from superfused strips of frog ventricle. Reducing the bathing calcium concentration ([Ca2+]0) with or without ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA) prolongs the action potential (AP). The change in the duration of the AP extends over many minutes, but is rapidly reversed by restoring calcium ions. Other changes (e.g., in resting potential and overshoot) are, however, only more slowly reversed. Reducing [Ca2+]0 with 0.2, 2, or 5 mM EGTA produces progressively greater prolongation of AP; maximum values were well in excess of 1 min. This prolongation can be reversed by other divalent cations in EGTA (Mg2+, Sr2+) or Ca-free (Mn2+) solutions, or by acetylcholine. Barium ions increase AP duration in keeping with their known effect on potassium conductance. D600, which blocks the slow inward current in cardiac muscle, is without effect on the action potentials recorded in EGTA solutions, or on the time course and extent of the recovery to normal duration upon restoring calcium ions. It is concluded that divalent cations exert an influence on membrane potassium conductance extracellularly in frog heart. The cell membrane does not become excessively \"leaky\" in EGTA solutions."}
{"id": "PMID:23409", "title": "Characterization of L-aspartate uptake by Streptomyces hydrogenans.", "content": "Multiple transport systems for L-aspartic acid exist in Steptomyces hydrogenans. The intracellular accumulation of L-aspartate against a concentration gradient was immediately inhibited by proton conductors, such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 2,4-dinitrophenol or nigericin. Transport activity was gradually lost when inhibitors of protein synthesis were added. L-Aspartate transport had two pH optima at 6.5 and 4.5. At pH 6.5, two saturable transport components with different Km and Vmax values could be resolved by kinetic studies. A high-affinity system (system I) preferred the L-isomers of the anionic forms of aspartic and glutamic acid. At the same pH, a second, low-affinity system (system II) operated, which was presumably less specific than system I and also able to accept, at high concentrations, neutral amino acids. At pH 4.5, the Lineweaver-Burk plot revealed only a single catalytic component, with Km and Vmax values similar to those of system II. Again, in contrast to system I, this component showed high affinity for neutral amino acids. The data suggest that L-aspartic acid and L-glutamic acid are transported by this system as neutral zwitterionic molecules.", "contents": "Characterization of L-aspartate uptake by Streptomyces hydrogenans. Multiple transport systems for L-aspartic acid exist in Steptomyces hydrogenans. The intracellular accumulation of L-aspartate against a concentration gradient was immediately inhibited by proton conductors, such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 2,4-dinitrophenol or nigericin. Transport activity was gradually lost when inhibitors of protein synthesis were added. L-Aspartate transport had two pH optima at 6.5 and 4.5. At pH 6.5, two saturable transport components with different Km and Vmax values could be resolved by kinetic studies. A high-affinity system (system I) preferred the L-isomers of the anionic forms of aspartic and glutamic acid. At the same pH, a second, low-affinity system (system II) operated, which was presumably less specific than system I and also able to accept, at high concentrations, neutral amino acids. At pH 4.5, the Lineweaver-Burk plot revealed only a single catalytic component, with Km and Vmax values similar to those of system II. Again, in contrast to system I, this component showed high affinity for neutral amino acids. The data suggest that L-aspartic acid and L-glutamic acid are transported by this system as neutral zwitterionic molecules."}
{"id": "PMID:23410", "title": "The mode of action of N-(n-Dodecyl)diethanolamine with particular reference to the effect of protonation on uptake by Escherichia coli.", "content": "In a homologous series of N-(n-alkyl)diethanolamines antimicrobial activity was related to surface activity and increasing octanol-water partition coefficient. Maximum activity was exhibited by the dodecyl-, tetradecyl- and hexadecyl-derivatives. Dodecyldiethanolamine (DDE) displayed a broad spectrum of activity. Towards Escherichia coli NCIB8277, its bacteriostatic and bactericidal activity increased as the degree of protonation lessened, and may have been influenced by the formation of micelles. Uptake of DDE by washed suspensions of E. coli was more rapid and more extensive at pH 7.0 than pH 4.0. Within this pH range, bacterial uptake, the octanol-water partition coefficient (lipid solubility) and the proportion of unprotonated DDE all increased. Uptake isotherms at pH values in the range 4.0 to 8.0 are interpreted as signifying different uptake mechanisms for the protonated and unprotonated forms.", "contents": "The mode of action of N-(n-Dodecyl)diethanolamine with particular reference to the effect of protonation on uptake by Escherichia coli. In a homologous series of N-(n-alkyl)diethanolamines antimicrobial activity was related to surface activity and increasing octanol-water partition coefficient. Maximum activity was exhibited by the dodecyl-, tetradecyl- and hexadecyl-derivatives. Dodecyldiethanolamine (DDE) displayed a broad spectrum of activity. Towards Escherichia coli NCIB8277, its bacteriostatic and bactericidal activity increased as the degree of protonation lessened, and may have been influenced by the formation of micelles. Uptake of DDE by washed suspensions of E. coli was more rapid and more extensive at pH 7.0 than pH 4.0. Within this pH range, bacterial uptake, the octanol-water partition coefficient (lipid solubility) and the proportion of unprotonated DDE all increased. Uptake isotherms at pH values in the range 4.0 to 8.0 are interpreted as signifying different uptake mechanisms for the protonated and unprotonated forms."}
{"id": "PMID:23419", "title": "Comparative digestibility of acid detergent fiber by laboratory albino and wild Polynesian rats.", "content": "The effects of adding 5%, 10%, and 15% acid detergent fiber to a nonfibrous basal diet were examined in a comparative feeding study with Polynesian rats (Rattus exulans) and laboratory rats. Digestibility coefficients for dry matter, crude protein, and gross energy declined significantly in both species as fiber content increased, but averaged significantly lower in the Polynesian than in the laboratory rat. Fiber digestibility was not significantly affected by fiber level but was by species, with the Polynesian rat having the higher digestibility coefficients.", "contents": "Comparative digestibility of acid detergent fiber by laboratory albino and wild Polynesian rats. The effects of adding 5%, 10%, and 15% acid detergent fiber to a nonfibrous basal diet were examined in a comparative feeding study with Polynesian rats (Rattus exulans) and laboratory rats. Digestibility coefficients for dry matter, crude protein, and gross energy declined significantly in both species as fiber content increased, but averaged significantly lower in the Polynesian than in the laboratory rat. Fiber digestibility was not significantly affected by fiber level but was by species, with the Polynesian rat having the higher digestibility coefficients."}
{"id": "PMID:23421", "title": "Fetal hypertension and the development of increased pulmonary vascular smooth muscle: a possible mechanism for persistent pulmonary hypertension of the newborn infant.", "content": "Chronic pulmonary arterial hypertension was produced in six fetal lambs. In four (126 to 139 days' gestation) unilateral fetal renal artery constriction caused systemic arterial mean blood pressure elevations. In another fetus, constriction of the umbilical artery caused a systemic mean blood pressure elevation; in the sixth, partial occlusion of the ductus arteriosus caused isolated pulmonary arterial hypertension. The right lung of each fetus was perfused with fixative at the in vivo mean arterial pressure and the amount of smooth muscle in the fifth generation (resistance) vessels analyzed using the medial width/external diameter ratio. There was a significant increase in the medial width/external diameter ratio in the six experimental animals as compared to that in six normal fetuses. In separate fetuses the increased ratios were due to a decreased external diameter, increased smooth muscle, or both these factors. The total number of resistance vessels was counted in the right lung of each fetus and no significant difference from normal was observed. We postulate that either fetal systemic hypertension or constriction of the ductus arteriosus causes fetal pulmonary hypertension in utero and that this produces increased smooth muscle development in pulmonary arterial resistance vessels; this may be a pathogenic mechanism for the syndrome of persistent pulmonary hypertension of the newborn infant.", "contents": "Fetal hypertension and the development of increased pulmonary vascular smooth muscle: a possible mechanism for persistent pulmonary hypertension of the newborn infant. Chronic pulmonary arterial hypertension was produced in six fetal lambs. In four (126 to 139 days' gestation) unilateral fetal renal artery constriction caused systemic arterial mean blood pressure elevations. In another fetus, constriction of the umbilical artery caused a systemic mean blood pressure elevation; in the sixth, partial occlusion of the ductus arteriosus caused isolated pulmonary arterial hypertension. The right lung of each fetus was perfused with fixative at the in vivo mean arterial pressure and the amount of smooth muscle in the fifth generation (resistance) vessels analyzed using the medial width/external diameter ratio. There was a significant increase in the medial width/external diameter ratio in the six experimental animals as compared to that in six normal fetuses. In separate fetuses the increased ratios were due to a decreased external diameter, increased smooth muscle, or both these factors. The total number of resistance vessels was counted in the right lung of each fetus and no significant difference from normal was observed. We postulate that either fetal systemic hypertension or constriction of the ductus arteriosus causes fetal pulmonary hypertension in utero and that this produces increased smooth muscle development in pulmonary arterial resistance vessels; this may be a pathogenic mechanism for the syndrome of persistent pulmonary hypertension of the newborn infant."}
{"id": "PMID:23422", "title": "Monitoring critically ill newborn infants with digital capillary blood samples: an alternative.", "content": "Capillary blood samples obtained from a warmed distal phalanx of the right hand were compared with either temporal or right radial arterial blood samples for PO2, PCO2, and pH in 33 critically ill newborn infants. The blood pressure and skin temperatures of each infant and the ambient oxygen concentration were recorded at the time the blood was sampled. Sixty-eight paired PO2 analyses yielded a regression line close to the line of identity. The mean difference between digital capillary and arterial PO2 was 11.3 +/- 1.4 mm Hg (r = 0.92). The results were similar for the paired PCO2 analyses (r = 0.84) and for the paired pH analyses (r = 0.94). The correlation between arterial PO2 and digital capillary PO2 deteriorated when the systolic blood pressure of the patient was below 35 mm Hg. There was no correlation between skin temperature and capillary-arterial PO2 differences. The frequency of retrolental fibroplasia leading to blindness was not different from that in nurseries that sample umbilical arterial blood routinely.", "contents": "Monitoring critically ill newborn infants with digital capillary blood samples: an alternative. Capillary blood samples obtained from a warmed distal phalanx of the right hand were compared with either temporal or right radial arterial blood samples for PO2, PCO2, and pH in 33 critically ill newborn infants. The blood pressure and skin temperatures of each infant and the ambient oxygen concentration were recorded at the time the blood was sampled. Sixty-eight paired PO2 analyses yielded a regression line close to the line of identity. The mean difference between digital capillary and arterial PO2 was 11.3 +/- 1.4 mm Hg (r = 0.92). The results were similar for the paired PCO2 analyses (r = 0.84) and for the paired pH analyses (r = 0.94). The correlation between arterial PO2 and digital capillary PO2 deteriorated when the systolic blood pressure of the patient was below 35 mm Hg. There was no correlation between skin temperature and capillary-arterial PO2 differences. The frequency of retrolental fibroplasia leading to blindness was not different from that in nurseries that sample umbilical arterial blood routinely."}
{"id": "PMID:23423", "title": "Physicochemical properties of glycyrrhizic acid in aqueous media II: Effect on flocculation-deflocculation behavior of suspensions of sulfathiazole and graphite.", "content": "The flocculation-deflocculation behavior of sulfathiazole and graphite in aqueous solutions of glycyrrhizic acid was studied by measuring the sedimentation volume and turbidity of supernates. The dispersing effect of glycyrrhizic acid on suspension of sulfathiazole showed a maximum in the pH 3-4 region, the same pH region where the zeta-potential of sulfathiazole particles showed a negative maximum. The results were explained by the variation of degrees of ionization of glycyrrhizic acid and sulfathiazole with pH. With graphite suspensions, the pH region where the dispersing effect of glycyrrhizic acid showed a maximum shifted to a higher pH compared with sulfathiazole. This result can be attributed to the fact that graphite is a nonpolar substance so the surface properties are not affected by a pH change. Hence, the adsorption of glycyrrhizic acid occurs even in a fairly high pH range.", "contents": "Physicochemical properties of glycyrrhizic acid in aqueous media II: Effect on flocculation-deflocculation behavior of suspensions of sulfathiazole and graphite. The flocculation-deflocculation behavior of sulfathiazole and graphite in aqueous solutions of glycyrrhizic acid was studied by measuring the sedimentation volume and turbidity of supernates. The dispersing effect of glycyrrhizic acid on suspension of sulfathiazole showed a maximum in the pH 3-4 region, the same pH region where the zeta-potential of sulfathiazole particles showed a negative maximum. The results were explained by the variation of degrees of ionization of glycyrrhizic acid and sulfathiazole with pH. With graphite suspensions, the pH region where the dispersing effect of glycyrrhizic acid showed a maximum shifted to a higher pH compared with sulfathiazole. This result can be attributed to the fact that graphite is a nonpolar substance so the surface properties are not affected by a pH change. Hence, the adsorption of glycyrrhizic acid occurs even in a fairly high pH range."}
{"id": "PMID:23424", "title": "Hydrolytic degradation of 2,6-dichlorobenzylthiopseudourea hydrochloride.", "content": "Degradation of 2,6-dichlorobenzylthiopseudourea hydrochloride was followed in basic medium (pH 7.5) to isolate and characterize all possible degradation products. IR, Raman, and NMR spectroscopy, TLC, and elemental analysis were used to identify the products. Degradation of base-hydrolyzed 2,6-dichlorobenzylthiopseudourea hydrochloride produced 2,6-dichlorobenzylthiol and cyanamide and was followed by oxidation (air) to produce bis(2,6-dichlorobenzyl) disulfide, dimerization to give cyanoguanidine, and hydrolysis to yield urea. The kinetics of hydrolysis at 22.5 degrees (pH 7.0 and 7.5) and at 37 degrees (pH 7.0) revealed a pseudo-first-order reaction with respect to the substrate. Apparent first-order rate constants and energy of activation, entropy of activation, and half-life values were determined.", "contents": "Hydrolytic degradation of 2,6-dichlorobenzylthiopseudourea hydrochloride. Degradation of 2,6-dichlorobenzylthiopseudourea hydrochloride was followed in basic medium (pH 7.5) to isolate and characterize all possible degradation products. IR, Raman, and NMR spectroscopy, TLC, and elemental analysis were used to identify the products. Degradation of base-hydrolyzed 2,6-dichlorobenzylthiopseudourea hydrochloride produced 2,6-dichlorobenzylthiol and cyanamide and was followed by oxidation (air) to produce bis(2,6-dichlorobenzyl) disulfide, dimerization to give cyanoguanidine, and hydrolysis to yield urea. The kinetics of hydrolysis at 22.5 degrees (pH 7.0 and 7.5) and at 37 degrees (pH 7.0) revealed a pseudo-first-order reaction with respect to the substrate. Apparent first-order rate constants and energy of activation, entropy of activation, and half-life values were determined."}
{"id": "PMID:23425", "title": "Improved colorimetric determination of aspirin and salicylic acid concentrations in human plasma.", "content": "An improvement in a previously described method for the determination of plasma salicylic acid and aspirin levels in humans is described. The procedure was simplified by employing only one plasma sample for both salicylates. More accurate estimation of salicylates, particularly aspirin, was achieved by using two different calibration curves. Salicylic acid was estimated by reaction with an aqueous solution of the Folin-Ciocalteu phenol reagent. Absorbance of the blue-colored complex, which formed on addition of sodium hydroxide, was measured at 670 nm. The influence of alkalinity in the formation of the colored complex is discussed. The average recovery of aspirin added to plasma was 94.61%; it was 214.72% by the previous method.", "contents": "Improved colorimetric determination of aspirin and salicylic acid concentrations in human plasma. An improvement in a previously described method for the determination of plasma salicylic acid and aspirin levels in humans is described. The procedure was simplified by employing only one plasma sample for both salicylates. More accurate estimation of salicylates, particularly aspirin, was achieved by using two different calibration curves. Salicylic acid was estimated by reaction with an aqueous solution of the Folin-Ciocalteu phenol reagent. Absorbance of the blue-colored complex, which formed on addition of sodium hydroxide, was measured at 670 nm. The influence of alkalinity in the formation of the colored complex is discussed. The average recovery of aspirin added to plasma was 94.61%; it was 214.72% by the previous method."}
{"id": "PMID:23428", "title": "An investigation of the ionic mechanism of intracellular pH regulation in mouse soleus muscle fibres.", "content": "1. Intracellular pH (pH(i)) of surface fibres of the mouse soleus muscle was measured in vitro by recessed-tip pH-sensitive micro-electrodes. pH(i) was displaced in an acid direction by removal of external (NH(4))(2)SO(4) after a short exposure, and the mechanism of recovery from this acidification was investigated.2. Removal of external K caused a very slow acidification (probably due to the decreasing Na gradient) but had no effect on the rate of pH(i) recovery following acidification. This indicates that K(+)-H(+) exchange is not involved in the pH(i) regulating system.3. Short applications of 10(-4)M ouabain had no obvious effect on pH(i) and did not alter the rate of pH(i) recovery following acidification. This suggests that there is no direct connexion between the regulation of pH(i) and the Na pump.4. Reduction of external Ca from 10 to 1 mM caused a transient fall in pH(i), but the rate of pH(i) recovery following acidification was unaffected. This suggests that Ca(2+)-H(+) exchange is not involved in the pH(i) regulating system.5. An 11% reduction in external Na caused a significant slowing of pH(i) recovery following acidification. 90% or complete removal of external Na almost stopped pH(i) recovery. This suggests that Na(+)-H(+) exchange is involved in pH(i) regulation.6. Amiloride (10(-4)M) reversibly reduced the rate of pH(i) recovery to much the same extent as removal of external Na. Its effect was not additive to that of removal of external Na.7. Internal Na ion concentration ([Na(+)](i)), measured using Na(+)-sensitive micro-electrodes, fell on application of (NH(4))(2)SO(4) and increased on its removal. The increase transiently raised [Na(+)](i) above the level recorded before (NH(4))(2)SO(4) application. This overshoot of [Na(+)](i) was almost completely inhibited by amiloride. This is consistent with the involvement of Na(+)-H(+) exchange in the pH(i) regulating system.8. Removal of external CO(2) or application of SITS (10(-4)M) caused some slowing of the rate of pH(i) recovery following acidification by removal of (NH(4))(2)SO(4). The effect of SITS was additive to that of Na-free Ringer or amiloride. These results suggest that Cl(-)-HCO(3) (-) exchange is also involved in the pH(i) regulating system and that it is a separate mechanism. Under the conditions used, Cl(-)-HCO(3) (-) exchange formed about 20% of the pH(i) regulating system.9. Decreasing the temperature from 37 to 28 degrees C not only caused an increase in pH(i), but also considerably slowed the rate of pH(i) recovery following acidification. We have calculated a Q(10) for Na(+)-H(+) exchange of 1.4 and for Cl(-)-HCO(3) (-) exchange, 6.9.10. We conclude that the pH(i) regulating system is comprised of two separate ionic exchange mechanisms. The major mechanism is Na(+)-H(+) exchange, which is probably driven by the transmembrane Na gradient. The other mechanism is Cl(-)-HCO(3) (-) exchange, which probably requires metabolic energy.", "contents": "An investigation of the ionic mechanism of intracellular pH regulation in mouse soleus muscle fibres. 1. Intracellular pH (pH(i)) of surface fibres of the mouse soleus muscle was measured in vitro by recessed-tip pH-sensitive micro-electrodes. pH(i) was displaced in an acid direction by removal of external (NH(4))(2)SO(4) after a short exposure, and the mechanism of recovery from this acidification was investigated.2. Removal of external K caused a very slow acidification (probably due to the decreasing Na gradient) but had no effect on the rate of pH(i) recovery following acidification. This indicates that K(+)-H(+) exchange is not involved in the pH(i) regulating system.3. Short applications of 10(-4)M ouabain had no obvious effect on pH(i) and did not alter the rate of pH(i) recovery following acidification. This suggests that there is no direct connexion between the regulation of pH(i) and the Na pump.4. Reduction of external Ca from 10 to 1 mM caused a transient fall in pH(i), but the rate of pH(i) recovery following acidification was unaffected. This suggests that Ca(2+)-H(+) exchange is not involved in the pH(i) regulating system.5. An 11% reduction in external Na caused a significant slowing of pH(i) recovery following acidification. 90% or complete removal of external Na almost stopped pH(i) recovery. This suggests that Na(+)-H(+) exchange is involved in pH(i) regulation.6. Amiloride (10(-4)M) reversibly reduced the rate of pH(i) recovery to much the same extent as removal of external Na. Its effect was not additive to that of removal of external Na.7. Internal Na ion concentration ([Na(+)](i)), measured using Na(+)-sensitive micro-electrodes, fell on application of (NH(4))(2)SO(4) and increased on its removal. The increase transiently raised [Na(+)](i) above the level recorded before (NH(4))(2)SO(4) application. This overshoot of [Na(+)](i) was almost completely inhibited by amiloride. This is consistent with the involvement of Na(+)-H(+) exchange in the pH(i) regulating system.8. Removal of external CO(2) or application of SITS (10(-4)M) caused some slowing of the rate of pH(i) recovery following acidification by removal of (NH(4))(2)SO(4). The effect of SITS was additive to that of Na-free Ringer or amiloride. These results suggest that Cl(-)-HCO(3) (-) exchange is also involved in the pH(i) regulating system and that it is a separate mechanism. Under the conditions used, Cl(-)-HCO(3) (-) exchange formed about 20% of the pH(i) regulating system.9. Decreasing the temperature from 37 to 28 degrees C not only caused an increase in pH(i), but also considerably slowed the rate of pH(i) recovery following acidification. We have calculated a Q(10) for Na(+)-H(+) exchange of 1.4 and for Cl(-)-HCO(3) (-) exchange, 6.9.10. We conclude that the pH(i) regulating system is comprised of two separate ionic exchange mechanisms. The major mechanism is Na(+)-H(+) exchange, which is probably driven by the transmembrane Na gradient. The other mechanism is Cl(-)-HCO(3) (-) exchange, which probably requires metabolic energy."}
{"id": "PMID:23429", "title": "The role of bicarbonate, chloride and sodium ions in the regulation of intracellular pH in snail neurones.", "content": "1. Intracellular pH (pH(i)), Cl(-) and Na(+) levels were recorded in snail neurones using ion-sensitive micro-electrodes, and the mechanism of the pH(i) recovery from internal acidification investigated.2. Reducing the external HCO(3) (-) concentration greatly inhibited the rate of pH(i) recovery from HCl injection.3. Reducing external Cl(-) did not inhibit pH(i) recovery, but reducing internal Cl(-), by exposing the cell to sulphate Ringer, inhibited pH(i) recovery from CO(2) application.4. During pH(i) recovery from CO(2) application the internal Cl(-) concentration decreased. The measured fall in internal Cl(-) concentration averaged about 25% of the calculated increase in internal HCO(3) (-).5. Removal of external Na inhibited the pH(i) recovery from either CO(2) application or HCl injection.6. During the pH(i) recovery from acidification there was an increase in the internal Na(+) concentration ([Na(+)](i)). The increase was larger than that occurring when the Na pump was inhibited by K-free Ringer.7. The increase in [Na(+)](i) that occurred during pH(i) recovery from an injection of HCl was about half of that produced by a similar injection of NaCl.8. The inhibitory effects of Na-free Ringer and of the anion exchange inhibitor SITS on pH(i) recovery after HCl injection were not additive.9. It is concluded that the pH(i) regulating system involves tightly linked Cl(-)-HCO(3) (-) and Na(+)-H(+) exchange, with Na entry down its concentration gradient probably providing the energy to drive the movement inwards of HCO(3) (-) and the movement outward of Cl(-) and H(+) ions.", "contents": "The role of bicarbonate, chloride and sodium ions in the regulation of intracellular pH in snail neurones. 1. Intracellular pH (pH(i)), Cl(-) and Na(+) levels were recorded in snail neurones using ion-sensitive micro-electrodes, and the mechanism of the pH(i) recovery from internal acidification investigated.2. Reducing the external HCO(3) (-) concentration greatly inhibited the rate of pH(i) recovery from HCl injection.3. Reducing external Cl(-) did not inhibit pH(i) recovery, but reducing internal Cl(-), by exposing the cell to sulphate Ringer, inhibited pH(i) recovery from CO(2) application.4. During pH(i) recovery from CO(2) application the internal Cl(-) concentration decreased. The measured fall in internal Cl(-) concentration averaged about 25% of the calculated increase in internal HCO(3) (-).5. Removal of external Na inhibited the pH(i) recovery from either CO(2) application or HCl injection.6. During the pH(i) recovery from acidification there was an increase in the internal Na(+) concentration ([Na(+)](i)). The increase was larger than that occurring when the Na pump was inhibited by K-free Ringer.7. The increase in [Na(+)](i) that occurred during pH(i) recovery from an injection of HCl was about half of that produced by a similar injection of NaCl.8. The inhibitory effects of Na-free Ringer and of the anion exchange inhibitor SITS on pH(i) recovery after HCl injection were not additive.9. It is concluded that the pH(i) regulating system involves tightly linked Cl(-)-HCO(3) (-) and Na(+)-H(+) exchange, with Na entry down its concentration gradient probably providing the energy to drive the movement inwards of HCO(3) (-) and the movement outward of Cl(-) and H(+) ions."}
{"id": "PMID:23430", "title": "Further evidence for adrenergic transmission in the human vas deferens.", "content": "1. Isolated portions of human vas deferens responded to field stimulation of the intramural nerve fibres or to exogenously applied noradrenaline with rhythmical contractions of both longitudinal and circular muscle layers. 2. In guinea-pig and rabbit vas deferens field stimulation produced an initial rapid 'twitch' response which was not found with human vasa. 3. Responses of the human vas to field stimulation were depressed by the alpha-adrenoceptor blocking agents phentolamine and yohimbine. 4. It is concluded that the motor innervation of the human vas deferens is adrenergic and the relevance of this to the physiological operation of the tissue is discussed.", "contents": "Further evidence for adrenergic transmission in the human vas deferens. 1. Isolated portions of human vas deferens responded to field stimulation of the intramural nerve fibres or to exogenously applied noradrenaline with rhythmical contractions of both longitudinal and circular muscle layers. 2. In guinea-pig and rabbit vas deferens field stimulation produced an initial rapid 'twitch' response which was not found with human vasa. 3. Responses of the human vas to field stimulation were depressed by the alpha-adrenoceptor blocking agents phentolamine and yohimbine. 4. It is concluded that the motor innervation of the human vas deferens is adrenergic and the relevance of this to the physiological operation of the tissue is discussed."}
{"id": "PMID:23431", "title": "The effect of foreign cations, pH and pharmacological agents on the ionic permeability of an excitatory glutamate synapse.", "content": "1. Voltage clamp studies of the post-synaptic membrane of the insect neuromuscular junction have shown that normal amplitude glutamate currents could be recorded for a limited time when external Na was completely replaced by Ca, Li, ammonium, methylamine and guanidine. No change in the reversal potential of the glutamate current was observed when Na was replaced by these ions. It is suggested that the glutamate ionic channel has a similar permeability to Na and to these foreign cations, although the foreign ions cause a longer-term block of the permeability increase or receptor function. 2. Procaine, pentobarbitone, 2-4-6-triaminopyrimidine, high and low pH and low temperature reduced the synaptic ionic permeability but did not alter the ratio of the conductance increase of Na to K (delta g Na/delta gK). 4-Aminopyridine and TEA did not reduce the synaptic ionic permeability. 3. The 3. The properties of the synaptic ionic channels resemble the tight junction transepithelial ionic channels of the mammalian gall-bladder, but are very different from the Na and K non-synaptic channels of axons. It is suggested that Na and K normally pass through a single relatively large channel containing strong proton accepting acidic ligands which render the channel cation selective.", "contents": "The effect of foreign cations, pH and pharmacological agents on the ionic permeability of an excitatory glutamate synapse. 1. Voltage clamp studies of the post-synaptic membrane of the insect neuromuscular junction have shown that normal amplitude glutamate currents could be recorded for a limited time when external Na was completely replaced by Ca, Li, ammonium, methylamine and guanidine. No change in the reversal potential of the glutamate current was observed when Na was replaced by these ions. It is suggested that the glutamate ionic channel has a similar permeability to Na and to these foreign cations, although the foreign ions cause a longer-term block of the permeability increase or receptor function. 2. Procaine, pentobarbitone, 2-4-6-triaminopyrimidine, high and low pH and low temperature reduced the synaptic ionic permeability but did not alter the ratio of the conductance increase of Na to K (delta g Na/delta gK). 4-Aminopyridine and TEA did not reduce the synaptic ionic permeability. 3. The 3. The properties of the synaptic ionic channels resemble the tight junction transepithelial ionic channels of the mammalian gall-bladder, but are very different from the Na and K non-synaptic channels of axons. It is suggested that Na and K normally pass through a single relatively large channel containing strong proton accepting acidic ligands which render the channel cation selective."}
{"id": "PMID:23433", "title": "Study of the structural requirements for dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide.", "content": "A number of analogs of the tripeptide L-prolyly-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide, or beta-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide (8) and L-prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide (9) showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide (11), on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotonin potentiation test.", "contents": "Study of the structural requirements for dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide. A number of analogs of the tripeptide L-prolyly-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide, or beta-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide (8) and L-prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide (9) showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide (11), on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotonin potentiation test."}
{"id": "PMID:23434", "title": "The ability of smooth and rough strains of Streptococcus pneumoniae to activate human complement by the alternative pathway.", "content": "Three capsulate pneumococcal strains of serotypes 1, 2 ans 3, and one non-capsulate strain of serotype 47, were found to activate human complement by the alternative pathway to a similar extent over the concentration range examined. Nevertheless, the capsulate strains, in contrast to the non-capsulate, are known to require complement attachment for phagocytosis and it is therefore postulated that the toxic by-products released cause the wave of oedema characteristic of pneumococcal lobar pneumonia.", "contents": "The ability of smooth and rough strains of Streptococcus pneumoniae to activate human complement by the alternative pathway. Three capsulate pneumococcal strains of serotypes 1, 2 ans 3, and one non-capsulate strain of serotype 47, were found to activate human complement by the alternative pathway to a similar extent over the concentration range examined. Nevertheless, the capsulate strains, in contrast to the non-capsulate, are known to require complement attachment for phagocytosis and it is therefore postulated that the toxic by-products released cause the wave of oedema characteristic of pneumococcal lobar pneumonia."}
{"id": "PMID:23435", "title": "The kinetic mechanism of action of an uncoupler of oxidative phosphorylation.", "content": "The chemiosmotic hypothesis predicts that the mechanism by which weak acids uncouple oxidative phosphorylation in mitochondria is identical to the mechanism by which they transport hydrogen ions across artificial bilayer membranes. We report here the results of a kinetic study of uncoupler-mediated hydrogen ion transport across bilayer membranes. We made electrical relaxation measurements on black lipid membranes exposed to the substituted benzimidazole 5,6-dichloro-2-trifluoromethylbenzimidazole. The simplest model consistent with our experimental data allowed us to deduce values for adsorption coefficients and rate constants. Our major conclusions are that the back diffusion of the neutral species is the rate limiting step for the steady state transport of hydrogen ions, that both the neutral and charged forms of the uncoupler adsorb strongly to the interfaces, and that the reactions at the membrane-solution interfaces occur sufficiently rapidly for equilibrium to be maintained. Independent measurements of the adsorption coefficients of both the neutral and anionic forms of the weak acid and also of the permeability of the membrane to the neutral form agreed well with the values deduced from the kinetic study.", "contents": "The kinetic mechanism of action of an uncoupler of oxidative phosphorylation. The chemiosmotic hypothesis predicts that the mechanism by which weak acids uncouple oxidative phosphorylation in mitochondria is identical to the mechanism by which they transport hydrogen ions across artificial bilayer membranes. We report here the results of a kinetic study of uncoupler-mediated hydrogen ion transport across bilayer membranes. We made electrical relaxation measurements on black lipid membranes exposed to the substituted benzimidazole 5,6-dichloro-2-trifluoromethylbenzimidazole. The simplest model consistent with our experimental data allowed us to deduce values for adsorption coefficients and rate constants. Our major conclusions are that the back diffusion of the neutral species is the rate limiting step for the steady state transport of hydrogen ions, that both the neutral and charged forms of the uncoupler adsorb strongly to the interfaces, and that the reactions at the membrane-solution interfaces occur sufficiently rapidly for equilibrium to be maintained. Independent measurements of the adsorption coefficients of both the neutral and anionic forms of the weak acid and also of the permeability of the membrane to the neutral form agreed well with the values deduced from the kinetic study."}
{"id": "PMID:23437", "title": "Endotoxin alters spontaneous transmitter release at the frog neuromuscular junction.", "content": "The direct neurotoxic effects of E. coli endotoxin (ETX) on spontaneous transmitter release were tested at the frog sartorius muscle neuromuscular junction. Spontaneous transmitter release was monitored by intracellularly recording miniature end-plate potentials (MEPPs). Junctions were continuously exposed to standard concentrations of 10 microgram/ml of 3 ETX samples, 2 of which produced a significant elevation of MEPP frequency followed by a decline of frequency to very low rates. The third ETX sample, known to have a decreased canine lethality, was without effect on MEPP frequency. No significant changes in MEPP amplitude were evident. The rate of change in MEPP frequency, but not the peak frequency, was reduced by lowering ETX concentrations. Alterations in MEPP frequency induced by ETX were prevented by removing Ca++ and antagonized by high [K+]out. The results suggest that ETX alters ion conductance channels, particularly those for Ca++, in the presynaptic terminal membrane.", "contents": "Endotoxin alters spontaneous transmitter release at the frog neuromuscular junction. The direct neurotoxic effects of E. coli endotoxin (ETX) on spontaneous transmitter release were tested at the frog sartorius muscle neuromuscular junction. Spontaneous transmitter release was monitored by intracellularly recording miniature end-plate potentials (MEPPs). Junctions were continuously exposed to standard concentrations of 10 microgram/ml of 3 ETX samples, 2 of which produced a significant elevation of MEPP frequency followed by a decline of frequency to very low rates. The third ETX sample, known to have a decreased canine lethality, was without effect on MEPP frequency. No significant changes in MEPP amplitude were evident. The rate of change in MEPP frequency, but not the peak frequency, was reduced by lowering ETX concentrations. Alterations in MEPP frequency induced by ETX were prevented by removing Ca++ and antagonized by high [K+]out. The results suggest that ETX alters ion conductance channels, particularly those for Ca++, in the presynaptic terminal membrane."}
{"id": "PMID:23439", "title": "Biochemical and morphological characterization of mycobacteriophage R1.", "content": "Large-scale propagation of mycobacteriophage R1 in broth culture has allowed the isolation of quantities of virus sufficient for characterization of its nucleic acid and lipid components as well as investigation of its ultrastructural attributes. Analysis of R1 DNA indicates that it is double stranded and possesses a molecular weight of 2.5 X 10(7) and a guanine-plus-cytosine content of 65.7 +/- 0.5%. The lipid fraction of R1 accounts for 14% of the total dry weight of the virus, 20% of which was identified as free or esterified sterols. A rapid loss of viral titer occurred after seconds of exposure to organic solvents. This result suggests that the lipid fractions of R1 is essential for its infectivity.  Electron microscopic investigation of solvent-extracted R1 showed extensive deterioration of its normal morphology, including nucleocapsid disintegration and base plate separation. Routine phosphotungstate preparations demonstrated a particle with an oval head and a noncontractile tail. Altering the pH of the phosphotungstate negative stain from neutrality damage the viral particles. Uranyl formate-contrasted specimens displayed an elongated hexagonal nucleocapsid with a neck region; the cross-striated tail possessed a starlike base plate.", "contents": "Biochemical and morphological characterization of mycobacteriophage R1. Large-scale propagation of mycobacteriophage R1 in broth culture has allowed the isolation of quantities of virus sufficient for characterization of its nucleic acid and lipid components as well as investigation of its ultrastructural attributes. Analysis of R1 DNA indicates that it is double stranded and possesses a molecular weight of 2.5 X 10(7) and a guanine-plus-cytosine content of 65.7 +/- 0.5%. The lipid fraction of R1 accounts for 14% of the total dry weight of the virus, 20% of which was identified as free or esterified sterols. A rapid loss of viral titer occurred after seconds of exposure to organic solvents. This result suggests that the lipid fractions of R1 is essential for its infectivity.  Electron microscopic investigation of solvent-extracted R1 showed extensive deterioration of its normal morphology, including nucleocapsid disintegration and base plate separation. Routine phosphotungstate preparations demonstrated a particle with an oval head and a noncontractile tail. Altering the pH of the phosphotungstate negative stain from neutrality damage the viral particles. Uranyl formate-contrasted specimens displayed an elongated hexagonal nucleocapsid with a neck region; the cross-striated tail possessed a starlike base plate."}
{"id": "PMID:23440", "title": "Transfection in pneumococcus: single-strand intermediates in the formation of infective centers.", "content": "Transfection has been found and characterized in pneumococcus. For replicating omega3 phage DNA extracted from infected cells, transfection was relatively efficient and rose linearly with DNA concentration and quadratically with time, according to T(T - 3.5) min(2). For mature DNA extracted from phage particles, transfection was hardly detectable below 1 mug/ml but increased about as the cube of the DNA concentration up to 100 mug/ml, and was still rising at concentrations over 200 mug/ml. The kinetics suggest a dependence on a mixed cubic function of the time of exposure of cells to mature DNA. Cell and phage DNAs competed with each other for transformation and transfection. Transfection was reduced much more strongly than transformation in cells that were deficient in the membrane-bound endonuclease required for conversion of donor duplex DNA to intracellular single strands; these data agree with the kinetic data in implying that independent entry of segments of two strands is necessary for transfection by replicating omega3 phage DNA and entry of at least three strands is necessary for transfection by mature DNA. To reconcile differing DNA concentration dependences of transfection and transformation with a common entry path, it was necessary to reexamine data on transformation and to recognize that this process continued to rise slowly through the concentration region usually described as \"plateau.\" These results and the transfection data reflect multiple binding and nicking events that occurred on the cell surface before entry. Our conclusion is that transfection in pneumococcus occurs by association inside the cell of segments of single strands of phage DNA that have entered independently, creating gapped structures that need repair synthesis to create infective centers. Physical recombination is therefore automatically a prerequisite to transfection.", "contents": "Transfection in pneumococcus: single-strand intermediates in the formation of infective centers. Transfection has been found and characterized in pneumococcus. For replicating omega3 phage DNA extracted from infected cells, transfection was relatively efficient and rose linearly with DNA concentration and quadratically with time, according to T(T - 3.5) min(2). For mature DNA extracted from phage particles, transfection was hardly detectable below 1 mug/ml but increased about as the cube of the DNA concentration up to 100 mug/ml, and was still rising at concentrations over 200 mug/ml. The kinetics suggest a dependence on a mixed cubic function of the time of exposure of cells to mature DNA. Cell and phage DNAs competed with each other for transformation and transfection. Transfection was reduced much more strongly than transformation in cells that were deficient in the membrane-bound endonuclease required for conversion of donor duplex DNA to intracellular single strands; these data agree with the kinetic data in implying that independent entry of segments of two strands is necessary for transfection by replicating omega3 phage DNA and entry of at least three strands is necessary for transfection by mature DNA. To reconcile differing DNA concentration dependences of transfection and transformation with a common entry path, it was necessary to reexamine data on transformation and to recognize that this process continued to rise slowly through the concentration region usually described as \"plateau.\" These results and the transfection data reflect multiple binding and nicking events that occurred on the cell surface before entry. Our conclusion is that transfection in pneumococcus occurs by association inside the cell of segments of single strands of phage DNA that have entered independently, creating gapped structures that need repair synthesis to create infective centers. Physical recombination is therefore automatically a prerequisite to transfection."}
{"id": "PMID:23441", "title": "XXY Klinefelter's syndrome with bilateral cryptochidism, obesity, multiple capillary hemangiomas and telangiectasia.", "content": "A case of XXY Klinefelter's syndrome associated with bilateral cryptochidism, -ultiple capillary hemangiomas and vesical telangiectasia is reported. Testicular biopsy revealed Leydig cell hyperplasia with hyalinization of the seminiferous tubular membrane. The patient presented with recurrent hematuria. Excretory urography, urethroscopy and renal angiography were normal. Cystoscopy revealed multiple telangiectasia, which was responsible for the hematuria. To our knowledge this is the first report of multiple capillary hemangiomas and vesical telangiectasia associated with calssical Klinefelter's syndrome.", "contents": "XXY Klinefelter's syndrome with bilateral cryptochidism, obesity, multiple capillary hemangiomas and telangiectasia. A case of XXY Klinefelter's syndrome associated with bilateral cryptochidism, -ultiple capillary hemangiomas and vesical telangiectasia is reported. Testicular biopsy revealed Leydig cell hyperplasia with hyalinization of the seminiferous tubular membrane. The patient presented with recurrent hematuria. Excretory urography, urethroscopy and renal angiography were normal. Cystoscopy revealed multiple telangiectasia, which was responsible for the hematuria. To our knowledge this is the first report of multiple capillary hemangiomas and vesical telangiectasia associated with calssical Klinefelter's syndrome."}
{"id": "PMID:23442", "title": "Acetohydroxamic acid: clinical studies of a urease inhibitor in patients with staghorn renal calculi.", "content": "The hydrolysis of urea by the bacterial enzyme urease pathologically increase urinary ammonia, bicarbonate, carconate and alkalinity. These factors contribute to the formation of urinary stones and to the virulence of bacteria. Acetohydroxamic acid, a potent inhibitor of urease, has been administered to 23 patients with staghorn renal calculi and urea-splitting urinary infection. Urinary ammonia and alkalinity has been reduced in every patient. A dose of 1.0 gm. acetohydroxamic acid daily has been well tolerated and effective for 2 to 12 months, even in patients with impaired renal function.", "contents": "Acetohydroxamic acid: clinical studies of a urease inhibitor in patients with staghorn renal calculi. The hydrolysis of urea by the bacterial enzyme urease pathologically increase urinary ammonia, bicarbonate, carconate and alkalinity. These factors contribute to the formation of urinary stones and to the virulence of bacteria. Acetohydroxamic acid, a potent inhibitor of urease, has been administered to 23 patients with staghorn renal calculi and urea-splitting urinary infection. Urinary ammonia and alkalinity has been reduced in every patient. A dose of 1.0 gm. acetohydroxamic acid daily has been well tolerated and effective for 2 to 12 months, even in patients with impaired renal function."}
{"id": "PMID:23449", "title": "[Determination of the individual changes in cardiovascular system reactivity in prescribing adrenergic blockaders].", "content": "The changes occurring in hemodynamics due to the effect of alpha-adreno-blocking agent pyrroxan and beta-blocking agent obzidan were studied in 20 patients with neurocirculatory dystonia and in 20 patients with stage IIB hypertensive disease. Forty healthy persons formed the control group. The results of the investigation allow for the assumption that a pharmacological test with a record of the transthoracic rheogram and the derivatives of the central pulse tracings help in the proper choice of the drug and its dosage with the state of hemodynamics and the inotropic myocardial reaction taken into account.", "contents": "[Determination of the individual changes in cardiovascular system reactivity in prescribing adrenergic blockaders]. The changes occurring in hemodynamics due to the effect of alpha-adreno-blocking agent pyrroxan and beta-blocking agent obzidan were studied in 20 patients with neurocirculatory dystonia and in 20 patients with stage IIB hypertensive disease. Forty healthy persons formed the control group. The results of the investigation allow for the assumption that a pharmacological test with a record of the transthoracic rheogram and the derivatives of the central pulse tracings help in the proper choice of the drug and its dosage with the state of hemodynamics and the inotropic myocardial reaction taken into account."}
{"id": "PMID:23468", "title": "Age related changes in muscle protein degradation.", "content": "In vitro autolytic degradation of sarcoplasmic proteins in red, white and cardiac muscles increases with advance in age and with increase in temperature, the rate varying with age. Higher activity is seen in the alkaline range in all age groups. Ca2+ activated proteolytic activity also increases with advance in age.", "contents": "Age related changes in muscle protein degradation. In vitro autolytic degradation of sarcoplasmic proteins in red, white and cardiac muscles increases with advance in age and with increase in temperature, the rate varying with age. Higher activity is seen in the alkaline range in all age groups. Ca2+ activated proteolytic activity also increases with advance in age."}
{"id": "PMID:23469", "title": "Changes of adrenal catecholamines and their synthesizing enzymes during ontogenesis and aging in rats.", "content": "Male Wistar specific-pathogen-free rats aged 2, 7, 17, 30, 60, 120, 200, 360 and 600 days, all killed in experiment on the same day, were examined. The body weight significantly increased until the 200th day, the weight of adrenals until the 120th day and the adrenal protein content until the 30th day of life. The adrenaline content of the adrenals increased continuously during the 600 days studied. Adrenal noradrenaline content increased rapidly over the first 17 days, remained at a stable level until the 120th day, and rose to a higher level after 200 days. The activity of adrenal catecholamine-synthesizing enzymes also increased with age: tyrosine hydroxylase gradually increased until the 360th day, dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase until the 200th day. Our results demonstrate that, in the rat, during development there is a gradual increase of adrenal weight, adrenaline content, tyrosine hydroxylase and phenylethanolamine-N-methyl transferase activity until maturation (120th day), whereas the adrenal noradrenaline content reaches the adult values earlier, around the 17th day. During aging, adrenal catecholamines significantly increase when compared to young-adult rats (120-day-old), probably due to the elevated activity of the adrenal catecholamine-synthesizing enzymes. The increased adrenal catecholamine levels in old animals might be connected with a higher incidence of cardiovascular diseases in aged.", "contents": "Changes of adrenal catecholamines and their synthesizing enzymes during ontogenesis and aging in rats. Male Wistar specific-pathogen-free rats aged 2, 7, 17, 30, 60, 120, 200, 360 and 600 days, all killed in experiment on the same day, were examined. The body weight significantly increased until the 200th day, the weight of adrenals until the 120th day and the adrenal protein content until the 30th day of life. The adrenaline content of the adrenals increased continuously during the 600 days studied. Adrenal noradrenaline content increased rapidly over the first 17 days, remained at a stable level until the 120th day, and rose to a higher level after 200 days. The activity of adrenal catecholamine-synthesizing enzymes also increased with age: tyrosine hydroxylase gradually increased until the 360th day, dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase until the 200th day. Our results demonstrate that, in the rat, during development there is a gradual increase of adrenal weight, adrenaline content, tyrosine hydroxylase and phenylethanolamine-N-methyl transferase activity until maturation (120th day), whereas the adrenal noradrenaline content reaches the adult values earlier, around the 17th day. During aging, adrenal catecholamines significantly increase when compared to young-adult rats (120-day-old), probably due to the elevated activity of the adrenal catecholamine-synthesizing enzymes. The increased adrenal catecholamine levels in old animals might be connected with a higher incidence of cardiovascular diseases in aged."}
{"id": "PMID:23470", "title": "Meningitis: the influence of routine otolaryngologic consultation on morbidity and mortality in 290 cases.", "content": "A prospective study was designed to obtain data on all meningitis patients admitted to a large county Communicable Disease Unit. The epidemiologic and clinical features of 290 cases were analyzed to ascertain the effect of routine O.R.L. consultation on the morbidity and mortality of this disease. The results of physical examination provided current statistics as to the existence of ear, nose, and throat diseases associated with meningitis.", "contents": "Meningitis: the influence of routine otolaryngologic consultation on morbidity and mortality in 290 cases. A prospective study was designed to obtain data on all meningitis patients admitted to a large county Communicable Disease Unit. The epidemiologic and clinical features of 290 cases were analyzed to ascertain the effect of routine O.R.L. consultation on the morbidity and mortality of this disease. The results of physical examination provided current statistics as to the existence of ear, nose, and throat diseases associated with meningitis."}
{"id": "PMID:23482", "title": "Renal function in patients with multiple myeloma.", "content": "Renal tubular and glomerular functions were evaluated in 35 consecutive patients with multiple myeloma and were correlated with changes in renal histopathology and myeloma protein patterns. All nine patients without Bence Jones proteinuria had CCr greater than 50 ml/min. In contrast 16/26 patients with Bence Jones proteinuria had CCr less than 50 ml/min and the magnitude of the Bence Jones proteinuria correlated well with the degree of renal insufficiency. Frequent abnormalities in renal tubular acidifying and concentrating ability were observed only in patients with Bence Jones proteinuria and occurred in the absence of significant reductions of glomerular filtration rate. Severely deranged renal histology was seen only in patients with Bence Jones proteinuria and consisted primarily of tubular atrophy and degeneration; glomeruli appeared normal. These data suggest that Bence Jones proteins exert a direct nephrotoxic effect at the tubular level with resultant tubular dysfunction and tubular atrophy. Glomerular filtration rate remains relatively preserved despite the significant abnormalities of tubular function. Although obstructing tubular casts were observed only in patients with severely impaired glomerular filtration rate, many patients with similarly impaired renal function had no evidence of such casts. Instead, tubular atrophy and degeneration correlated best with renal dysfunction.", "contents": "Renal function in patients with multiple myeloma. Renal tubular and glomerular functions were evaluated in 35 consecutive patients with multiple myeloma and were correlated with changes in renal histopathology and myeloma protein patterns. All nine patients without Bence Jones proteinuria had CCr greater than 50 ml/min. In contrast 16/26 patients with Bence Jones proteinuria had CCr less than 50 ml/min and the magnitude of the Bence Jones proteinuria correlated well with the degree of renal insufficiency. Frequent abnormalities in renal tubular acidifying and concentrating ability were observed only in patients with Bence Jones proteinuria and occurred in the absence of significant reductions of glomerular filtration rate. Severely deranged renal histology was seen only in patients with Bence Jones proteinuria and consisted primarily of tubular atrophy and degeneration; glomeruli appeared normal. These data suggest that Bence Jones proteins exert a direct nephrotoxic effect at the tubular level with resultant tubular dysfunction and tubular atrophy. Glomerular filtration rate remains relatively preserved despite the significant abnormalities of tubular function. Although obstructing tubular casts were observed only in patients with severely impaired glomerular filtration rate, many patients with similarly impaired renal function had no evidence of such casts. Instead, tubular atrophy and degeneration correlated best with renal dysfunction."}
{"id": "PMID:23483", "title": "X-linked recessive (Duchenne) muscular dystrophy (DMD) and purine metabolism: effects of oral allopurinol and adenylate.", "content": "Data are presented which suggest that Duchenne muscular dystrophy (DMD) may have some origin in a severe deficiency of total muscle adenine nucleotides. Using double-blind techniques, this possibility was tested in 16 DMD patients by giving oral allopurinol, a synthetic inhibitor of the purine catabolic enzyme xanthine oxidase. Sublingual procaine adenylate was also briefly tested. Instances of clinical improvement quickly occurred which were statistically significant; they were accompanied by a significant increase in physical strength. These improvements have been maintained for more than 6 mo by administration of a small amount of allopurinol daily. Procaine adenylate had little effect. These results support the above view of DMD and seem to indicate that existing purines, retained and recycled after allopurinol, can sustain such improvement, and that additional adenylate is unnecessary.", "contents": "X-linked recessive (Duchenne) muscular dystrophy (DMD) and purine metabolism: effects of oral allopurinol and adenylate. Data are presented which suggest that Duchenne muscular dystrophy (DMD) may have some origin in a severe deficiency of total muscle adenine nucleotides. Using double-blind techniques, this possibility was tested in 16 DMD patients by giving oral allopurinol, a synthetic inhibitor of the purine catabolic enzyme xanthine oxidase. Sublingual procaine adenylate was also briefly tested. Instances of clinical improvement quickly occurred which were statistically significant; they were accompanied by a significant increase in physical strength. These improvements have been maintained for more than 6 mo by administration of a small amount of allopurinol daily. Procaine adenylate had little effect. These results support the above view of DMD and seem to indicate that existing purines, retained and recycled after allopurinol, can sustain such improvement, and that additional adenylate is unnecessary."}
{"id": "PMID:23484", "title": "[Kinetics of constitutive synthesis of polymethylgalacturonases by Penicillium digitatum as a function of the carbon source and pH].", "content": "Constitutive biosynthesis of polymethylgalacturonases by Penicillium digitatum is most active at the postexponential growth phase. Under certain conditions, the enzymes are synthesized at the constant rate which does not depend on the conditions of nutrition of the producing culture. An increase in the concentration of H+ ions at pH 3.0 changes the character of the fungal growth, prolongs the lag phase, decreases the rate of growth and increases the rate of the enzyme synthesis. The growth rate of Penicillium digitatum does not determine the rate of the enzyme synthesis. The enzyme synthesis does not depend on the conditions of the cultural growth.", "contents": "[Kinetics of constitutive synthesis of polymethylgalacturonases by Penicillium digitatum as a function of the carbon source and pH]. Constitutive biosynthesis of polymethylgalacturonases by Penicillium digitatum is most active at the postexponential growth phase. Under certain conditions, the enzymes are synthesized at the constant rate which does not depend on the conditions of nutrition of the producing culture. An increase in the concentration of H+ ions at pH 3.0 changes the character of the fungal growth, prolongs the lag phase, decreases the rate of growth and increases the rate of the enzyme synthesis. The growth rate of Penicillium digitatum does not determine the rate of the enzyme synthesis. The enzyme synthesis does not depend on the conditions of the cultural growth."}
{"id": "PMID:23489", "title": "A controlled comparative trial of clorazepate (Tranxene) and diazepam (Valium) for anxiety.", "content": "Two groups of anxious patients were treated with either clorazepate (n = 27, 15 mg at night), or diazepam (n = 27, 5 mg three times a day), and the anxiolytic effects of the treatments compared during a 22 day period. Both drugs were effective antianxiety agents (as assessed by the Hamilton Anxiety Scale, Analogue and Rapid Symptom Check List scales). The response to drug treatment did not differ according to the type of anxiety--psychological or somatic. No significant difference was observed between the two drug treatments. Separation of patients according to their anxiety type did not change this finding. Clorazepate, when administered as a single dose at night, is an effective short term anxiolytic.", "contents": "A controlled comparative trial of clorazepate (Tranxene) and diazepam (Valium) for anxiety. Two groups of anxious patients were treated with either clorazepate (n = 27, 15 mg at night), or diazepam (n = 27, 5 mg three times a day), and the anxiolytic effects of the treatments compared during a 22 day period. Both drugs were effective antianxiety agents (as assessed by the Hamilton Anxiety Scale, Analogue and Rapid Symptom Check List scales). The response to drug treatment did not differ according to the type of anxiety--psychological or somatic. No significant difference was observed between the two drug treatments. Separation of patients according to their anxiety type did not change this finding. Clorazepate, when administered as a single dose at night, is an effective short term anxiolytic."}
{"id": "PMID:23485", "title": "[Relationship between spore formation and synthesis of extracellular protheases in Bacillus mesentericus].", "content": "Two phases were established in the synthesis of extracellular proteases by Bacillus mesentericus 73. When the growth rate was high, the synthesis of proteases was small. The maximum rate of the enzyme synthesis was observed when the growth decelerated and the production of spores started. The synthesis of alkaline protease and the formation of spores are susceptible to nitrogen-metabolite and catabolite repression. The ability to produce spores was not found in the S variant of Bacillus mesentericus that did not synthesize extracellular proteases.", "contents": "[Relationship between spore formation and synthesis of extracellular protheases in Bacillus mesentericus]. Two phases were established in the synthesis of extracellular proteases by Bacillus mesentericus 73. When the growth rate was high, the synthesis of proteases was small. The maximum rate of the enzyme synthesis was observed when the growth decelerated and the production of spores started. The synthesis of alkaline protease and the formation of spores are susceptible to nitrogen-metabolite and catabolite repression. The ability to produce spores was not found in the S variant of Bacillus mesentericus that did not synthesize extracellular proteases."}
{"id": "PMID:23486", "title": "[Energy characteristics of the stages of photo-dependent transport of 14C-alanine in Halobacterium halobium R1 cells].", "content": "The energy of light is utilized by Halobacterium halobium R1 only at the very beginning of illumination at the same time as the transport of protons into the cells, as follows from comparing the data of photophosphorylation and light-dependent transport. The release of protons by the cells on further illumination suggests that the photoprocess and the accumulation of energy by the cells are being uncoupled. The primary transport of 15C-alanine in the course of illumination is caused directly by electrochemical gradient (i) whereas the secondary transport in the dark involves the energy liberated on hydrolysis of ATP which has been formed in the process of photophosphorylation (II). An indirect technique of assaying ATP from the transport of 14C-alanine into the cells makes it possible to characterize the distribution of utilized light energy between photophosphorylation (II) and transport processes (I). The bulk of energy is accumulated as ATP. The incorporation of 14C-alanine into the cells is stimulated twofold by illumination for a long time under physiological conditions in the presence of respiration. Therefore, light plays an important role in the energy balance of H. halobium R1.", "contents": "[Energy characteristics of the stages of photo-dependent transport of 14C-alanine in Halobacterium halobium R1 cells]. The energy of light is utilized by Halobacterium halobium R1 only at the very beginning of illumination at the same time as the transport of protons into the cells, as follows from comparing the data of photophosphorylation and light-dependent transport. The release of protons by the cells on further illumination suggests that the photoprocess and the accumulation of energy by the cells are being uncoupled. The primary transport of 15C-alanine in the course of illumination is caused directly by electrochemical gradient (i) whereas the secondary transport in the dark involves the energy liberated on hydrolysis of ATP which has been formed in the process of photophosphorylation (II). An indirect technique of assaying ATP from the transport of 14C-alanine into the cells makes it possible to characterize the distribution of utilized light energy between photophosphorylation (II) and transport processes (I). The bulk of energy is accumulated as ATP. The incorporation of 14C-alanine into the cells is stimulated twofold by illumination for a long time under physiological conditions in the presence of respiration. Therefore, light plays an important role in the energy balance of H. halobium R1."}
{"id": "PMID:23487", "title": "[Cyclic pathway of formaldehyde oxidation in Pseudomonas oleovorans].", "content": "Operation of the dissimilatory hexulose phosphate cycle of formaldehyde oxidation in Pseudomonas oleovarans has been directly confirmed. Extracts of this typical facultative methylotroph catalyze the formation of 14CO2 from 14C-formaldehyde. The process depends on the presence of ribose-5-phosphate, NADP or NAD, and is linear in time. Oxidation of formaldehyde via formate to CO2 is of a minor importance in the energy metabolism of the methylotroph.", "contents": "[Cyclic pathway of formaldehyde oxidation in Pseudomonas oleovorans]. Operation of the dissimilatory hexulose phosphate cycle of formaldehyde oxidation in Pseudomonas oleovarans has been directly confirmed. Extracts of this typical facultative methylotroph catalyze the formation of 14CO2 from 14C-formaldehyde. The process depends on the presence of ribose-5-phosphate, NADP or NAD, and is linear in time. Oxidation of formaldehyde via formate to CO2 is of a minor importance in the energy metabolism of the methylotroph."}
{"id": "PMID:23491", "title": "Increased and decreased sensitivity to carbon catabolite repression of enzymes of acetate metabolism in mutants of Aspergillus nidulans.", "content": "The creA204, creB15 and creC27 mutations have been shown to cause carbon catabolite derepression of acetly CoA synthase and isocitrate lyase in Aspergillus nidulans. A recessive mutation, cre-34, which is linked to the creC gene, results in these enzymes being more sensitive than cre or wildtype strains to catabolite repression. The acetamidase levels of strains containing cre mutations have been investigated and provide support for the hypothesis that an acetate metabolite, rather than acetamide, induces this enzyme.", "contents": "Increased and decreased sensitivity to carbon catabolite repression of enzymes of acetate metabolism in mutants of Aspergillus nidulans. The creA204, creB15 and creC27 mutations have been shown to cause carbon catabolite derepression of acetly CoA synthase and isocitrate lyase in Aspergillus nidulans. A recessive mutation, cre-34, which is linked to the creC gene, results in these enzymes being more sensitive than cre or wildtype strains to catabolite repression. The acetamidase levels of strains containing cre mutations have been investigated and provide support for the hypothesis that an acetate metabolite, rather than acetamide, induces this enzyme."}
{"id": "PMID:23493", "title": "[Clobazam (Frisium) in everyday practice. An open six-months' study of its efficacy and tolerance (author's transl)].", "content": "Fifty patients suffering principally from neurotic and psychosomatic disturbances were treated for 6 months with an average of 30 mg clobazam (Frisium) per day. For documentation of the efficacy and tolerance a set of assessment scales and procedures from the ECDEU system (Early Clinical Drug Evaluation Unit) was compiled. The results showed unanimously the anxiolytic efficacy and good tolerance of clobaza. After the second week of treatment there was a significant reduction in the anxiety symptoms in the judgement of the doctor and patient (p less than 0.01). Parallel to the reduction of anxiety symptoms the general condition also improved. The good tolerance of clobazam was shown in the overall clinical assessment and in the recording of specific side effects, which could never be called severe in any case. Moreover, there were no suggestions of changes in tolerance of of dependency.", "contents": "[Clobazam (Frisium) in everyday practice. An open six-months' study of its efficacy and tolerance (author's transl)]. Fifty patients suffering principally from neurotic and psychosomatic disturbances were treated for 6 months with an average of 30 mg clobazam (Frisium) per day. For documentation of the efficacy and tolerance a set of assessment scales and procedures from the ECDEU system (Early Clinical Drug Evaluation Unit) was compiled. The results showed unanimously the anxiolytic efficacy and good tolerance of clobaza. After the second week of treatment there was a significant reduction in the anxiety symptoms in the judgement of the doctor and patient (p less than 0.01). Parallel to the reduction of anxiety symptoms the general condition also improved. The good tolerance of clobazam was shown in the overall clinical assessment and in the recording of specific side effects, which could never be called severe in any case. Moreover, there were no suggestions of changes in tolerance of of dependency."}
{"id": "PMID:23495", "title": "Efficiency and cost of primary care by nurses and physician assistants.", "content": "We conducted a prospective study in a prepaid primary-care practice (health-maintenance organization) of a system in which nurses and physician assistants used protocols, and compared the efficiency and costs of this \"new-health-practitioner\" protocol system to a physician-only nonprotocol system. In five months, we studied 472 patients with any of four common acute complaints--respiratory infections, urinary and vaginal infections, headache, and abdominal pain; a subset of 203 patients was randomly allocated between the two systems. In the new-health-practitioner system physician time per patient was reduced by 92 per cent, from 11.8 to 0.9 minutes, and average visit costs--including practitioner time and charges for laboratory tests and medications--were 20 per cent less (P = 0.01). We conclude that this protocol system saves physician time and reduces costs.", "contents": "Efficiency and cost of primary care by nurses and physician assistants. We conducted a prospective study in a prepaid primary-care practice (health-maintenance organization) of a system in which nurses and physician assistants used protocols, and compared the efficiency and costs of this \"new-health-practitioner\" protocol system to a physician-only nonprotocol system. In five months, we studied 472 patients with any of four common acute complaints--respiratory infections, urinary and vaginal infections, headache, and abdominal pain; a subset of 203 patients was randomly allocated between the two systems. In the new-health-practitioner system physician time per patient was reduced by 92 per cent, from 11.8 to 0.9 minutes, and average visit costs--including practitioner time and charges for laboratory tests and medications--were 20 per cent less (P = 0.01). We conclude that this protocol system saves physician time and reduces costs."}
{"id": "PMID:23500", "title": "Analysis of the beta-receptor mediated effect on fast-contracting skeletal muscle in vitro.", "content": "Subtetanic contractions of the isolated extensor digitorum longus (EDL) of the guinea-pig, a fast-contracting muscle, were evoked by transmural field stimulation. Isoprenaline, adrenaline, terbutaline, and noradrenaline each caused a dose-dependent increase in the force of contraction, their potencies decreasing in that order. Tyramine was without effect in this respect. Curare depressed the contractions of EDL by about 20% but did not appreciably change the response to the beta-adrenoceptor agonists. The effects of isoprenaline and noradrenaline were blocked by propranolol (unselective) and H 35/25 (1-(p-tolyl)-2-isopropylamino-1-propanol, beta2-selective) but not by practolol (beta1-selective). Moreover, the increase in the force of subtetanic contractions of EDL produced by noradrenaline was unaffected by phentolamine. It is concluded that the adrenoceptor mediating the increase in the force of contraction of the isolated EDL is of the beta2-type and that the site of action is direct on the muscle. Its similarity to the receptor mediating the inverse effect on the slow-contracting soleus-muscle is pointed out.", "contents": "Analysis of the beta-receptor mediated effect on fast-contracting skeletal muscle in vitro. Subtetanic contractions of the isolated extensor digitorum longus (EDL) of the guinea-pig, a fast-contracting muscle, were evoked by transmural field stimulation. Isoprenaline, adrenaline, terbutaline, and noradrenaline each caused a dose-dependent increase in the force of contraction, their potencies decreasing in that order. Tyramine was without effect in this respect. Curare depressed the contractions of EDL by about 20% but did not appreciably change the response to the beta-adrenoceptor agonists. The effects of isoprenaline and noradrenaline were blocked by propranolol (unselective) and H 35/25 (1-(p-tolyl)-2-isopropylamino-1-propanol, beta2-selective) but not by practolol (beta1-selective). Moreover, the increase in the force of subtetanic contractions of EDL produced by noradrenaline was unaffected by phentolamine. It is concluded that the adrenoceptor mediating the increase in the force of contraction of the isolated EDL is of the beta2-type and that the site of action is direct on the muscle. Its similarity to the receptor mediating the inverse effect on the slow-contracting soleus-muscle is pointed out."}
{"id": "PMID:23503", "title": "Effect of 5-hydroxytryptophan on prolactin and growth hormone release in the infant rat: evidence for different neurotransmitter mediation.", "content": "In 10 day-old female and male rats, administration of 5-hydroxytryptophan (5-HTP) induced a prompt elevation in plasma prolactin (Prl) and growth hormone (GH) levels. Pretreatment with 2 serotonin (5-HT) receptor blockers, methysergide (Meth) and metergoline (MCE), markedly reduced the 5-HTP-induced Prl rise but failed to alter the GH response to 5-HTP. Administration of 2 selective inhibitors of presynaptic 5-HT reuptake, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenyl-propylamine and chlorimipramine (CIM), potentiated the 5-HTP-stimulated Prl rise but significantly reduced the 5-HTP-induced GH release. Blockade of dopaminergic or alpha-adrenergic receptors by pretreatment with pimozide (Pim) or phentolamine (Phent), respectively, or central sympathectomy by intraventricularly (i.vt.) injected 6-hydroxydopamine (6-OHDA) were capable of reducing the 5-HTP-induced GH release without affecting the 5-HTP-induced Prl rise. These data indicate that in the infant rat the 5-HTP-induced Prl release is mediated via the brain 5-HT system and that a nonspecific activation of the catecholaminergic system is responsible for the GH response to the drug.", "contents": "Effect of 5-hydroxytryptophan on prolactin and growth hormone release in the infant rat: evidence for different neurotransmitter mediation. In 10 day-old female and male rats, administration of 5-hydroxytryptophan (5-HTP) induced a prompt elevation in plasma prolactin (Prl) and growth hormone (GH) levels. Pretreatment with 2 serotonin (5-HT) receptor blockers, methysergide (Meth) and metergoline (MCE), markedly reduced the 5-HTP-induced Prl rise but failed to alter the GH response to 5-HTP. Administration of 2 selective inhibitors of presynaptic 5-HT reuptake, 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenyl-propylamine and chlorimipramine (CIM), potentiated the 5-HTP-stimulated Prl rise but significantly reduced the 5-HTP-induced GH release. Blockade of dopaminergic or alpha-adrenergic receptors by pretreatment with pimozide (Pim) or phentolamine (Phent), respectively, or central sympathectomy by intraventricularly (i.vt.) injected 6-hydroxydopamine (6-OHDA) were capable of reducing the 5-HTP-induced GH release without affecting the 5-HTP-induced Prl rise. These data indicate that in the infant rat the 5-HTP-induced Prl release is mediated via the brain 5-HT system and that a nonspecific activation of the catecholaminergic system is responsible for the GH response to the drug."}
{"id": "PMID:23501", "title": "[New anti-migraine drugs used in the treatment of children and adolescents].", "content": "In recent years a number of new preparations from the group of antiserotonin agents (including cyproheptadine and carbazochrome) as well as beta-adrenergic blocking agents (propranolol) and clonidine have been introduced for prevention of migraine and similar headaches. The efficiency of these drugs was studied in a group of 9 selected cases--adolescents with severe migraine refractory to other methods of treatment. In 7 cases the improvement was noted. The results were compared with own observations on larger groups of adults and data from literature. Too small number of observed patients made impossible definite conclusions. It seems, however that in selected cases the use of these drugs in headaches of adolescents is useful.", "contents": "[New anti-migraine drugs used in the treatment of children and adolescents]. In recent years a number of new preparations from the group of antiserotonin agents (including cyproheptadine and carbazochrome) as well as beta-adrenergic blocking agents (propranolol) and clonidine have been introduced for prevention of migraine and similar headaches. The efficiency of these drugs was studied in a group of 9 selected cases--adolescents with severe migraine refractory to other methods of treatment. In 7 cases the improvement was noted. The results were compared with own observations on larger groups of adults and data from literature. Too small number of observed patients made impossible definite conclusions. It seems, however that in selected cases the use of these drugs in headaches of adolescents is useful."}
{"id": "PMID:23507", "title": "[The human factor as a cause of flight accidents].", "content": "Four causes of flying accidents due to human factors are discussed: physical and psycological unfitness, insufficient physical and psychological training, and flight fatigue. Ways in which these factors can be eliminated or their effects diminished are indicated, including the establishment of a national aeronautical health service manned by physicians specialising in aerospace medicine.", "contents": "[The human factor as a cause of flight accidents]. Four causes of flying accidents due to human factors are discussed: physical and psycological unfitness, insufficient physical and psychological training, and flight fatigue. Ways in which these factors can be eliminated or their effects diminished are indicated, including the establishment of a national aeronautical health service manned by physicians specialising in aerospace medicine."}
{"id": "PMID:23508", "title": "Enzymic detection of metachromatic leukodystrophy patients and heterozygotes.", "content": "Two unrelated families with metachromatic leukodystrophy have been examined for the leukocyte enzyme arylsufatase A. The enzyme activities clearly reflect an autosomal recessive mode of inherence. All four parents showed heterozygote enzyme levels 40-60 percent of the control range while the two affected children had less than 20 percent normal activity. The two sibs of one affected child were shown to be heterozygote carriers. A simple screening method for sulfatase activity in tears has been developed which distinguished between metachromatic leukodystrophy patients and a control population which included other neurological disorders. Enzyme screening on tears may also be used to detect other lysosomal storage diseases including Tay-Sachs and Fabry disease.", "contents": "Enzymic detection of metachromatic leukodystrophy patients and heterozygotes. Two unrelated families with metachromatic leukodystrophy have been examined for the leukocyte enzyme arylsufatase A. The enzyme activities clearly reflect an autosomal recessive mode of inherence. All four parents showed heterozygote enzyme levels 40-60 percent of the control range while the two affected children had less than 20 percent normal activity. The two sibs of one affected child were shown to be heterozygote carriers. A simple screening method for sulfatase activity in tears has been developed which distinguished between metachromatic leukodystrophy patients and a control population which included other neurological disorders. Enzyme screening on tears may also be used to detect other lysosomal storage diseases including Tay-Sachs and Fabry disease."}
{"id": "PMID:23509", "title": "The treatment of peptic ulcer.", "content": "Recent evaluation of the time honoured use of antacids and anticholinergics in the treatment of peptic ulcer disease has not revealed persuasive evidence of efficacy above that of placebo. New drugs becoming available as medical treatments of peptic ulcer disease, viz H2-receptor antagonists and E group prostaglandin analogues, show considerable promise but require more time for adequate evaluation. The surgical treatment of peptic ulcer disease has similarly evolved with the development of effective operations with minimal post surgical morbidity, but again await the test of time for adequate evaluation.", "contents": "The treatment of peptic ulcer. Recent evaluation of the time honoured use of antacids and anticholinergics in the treatment of peptic ulcer disease has not revealed persuasive evidence of efficacy above that of placebo. New drugs becoming available as medical treatments of peptic ulcer disease, viz H2-receptor antagonists and E group prostaglandin analogues, show considerable promise but require more time for adequate evaluation. The surgical treatment of peptic ulcer disease has similarly evolved with the development of effective operations with minimal post surgical morbidity, but again await the test of time for adequate evaluation."}
{"id": "PMID:23511", "title": "Localization of substance P-like immunoreactivity in nerves in the tooth pulp.", "content": "The occurrence of substance P (SP)-like immunoreactivity was studied in dental pulps of the cat. In untreated animals SP-positive fibres were found in all areas of the pulp. Most fibres were seen in central parts of the pulp but they were also observed in relation to the odontoblasts. Single, possibly unmyelinated, or fine caliber fibres or small bundles of them were seen running close to large non-fluorescent myelinated nerves, to blood vessels or without any obvious association with either of these structures. Fourteen days after transection of the inferior alveolar nerve no SP-positive fibres were observed in pulps on the denervated side. Transection of the cervical sympathetic ganglion did not change the occurrence of SP-positive fibres. The results indicate the existence of at least two types of afferent fibres in the dental pulp of the cat. Since the tooth pulp has been demonstrated to give rise only to pain sensation when stimulated, the results give morphological support for a role of SP neurones in pain transmission.", "contents": "Localization of substance P-like immunoreactivity in nerves in the tooth pulp. The occurrence of substance P (SP)-like immunoreactivity was studied in dental pulps of the cat. In untreated animals SP-positive fibres were found in all areas of the pulp. Most fibres were seen in central parts of the pulp but they were also observed in relation to the odontoblasts. Single, possibly unmyelinated, or fine caliber fibres or small bundles of them were seen running close to large non-fluorescent myelinated nerves, to blood vessels or without any obvious association with either of these structures. Fourteen days after transection of the inferior alveolar nerve no SP-positive fibres were observed in pulps on the denervated side. Transection of the cervical sympathetic ganglion did not change the occurrence of SP-positive fibres. The results indicate the existence of at least two types of afferent fibres in the dental pulp of the cat. Since the tooth pulp has been demonstrated to give rise only to pain sensation when stimulated, the results give morphological support for a role of SP neurones in pain transmission."}
{"id": "PMID:23512", "title": "Gamete development in malaria parasites: bicarbonate-dependent stimulation by pH in vitro.", "content": "Gametogenesis in Plasmodium gallinaceum involves bicarbonate-dependent processes and requires a continuous supply of glucose (presumably as an energy source). Emergence and exflagellation of gametocytes, in vitro, occur independently of the CO2 tension but are rigidly correlated with the pH of the external medium. In bicarbonate-saline gametogenesis is initiated only if the pH exceeds 7.7. Our results suggest that gamete development of malaria parasites is stimulated when infected blood is exposed to air because the decrease in the CO2 tension of the blood causes its pH to rise.", "contents": "Gamete development in malaria parasites: bicarbonate-dependent stimulation by pH in vitro. Gametogenesis in Plasmodium gallinaceum involves bicarbonate-dependent processes and requires a continuous supply of glucose (presumably as an energy source). Emergence and exflagellation of gametocytes, in vitro, occur independently of the CO2 tension but are rigidly correlated with the pH of the external medium. In bicarbonate-saline gametogenesis is initiated only if the pH exceeds 7.7. Our results suggest that gamete development of malaria parasites is stimulated when infected blood is exposed to air because the decrease in the CO2 tension of the blood causes its pH to rise."}
{"id": "PMID:23520", "title": "[The sympathetic nervous system inhibition in the antihypertensive effect of beta-blockers (author's transl)].", "content": "The decrease of sympathetic activity by the beta-blocking drug, as demonstrated by the decreased electric activity of the splanchnic nerve and by the decreased urinary catecholamine reponse to tilt as well as by the decreased levels of plasma dopamine beta-hydroxylase exists not only in hypertension with elevated PRA but also in hypertension with normal or low PRA. In these latter cases the antihypertensive effect is better explained by the decrease in the sympathetic nervous system activity than by the decrease of PRA. This effect seems to be indirect and probably, as suggested by Lewis, as a result of damping sensory input to the central nervous system from the heart, whose capacity to respond to exercice and stress is blunted by beta-adreno-receptor blockade.", "contents": "[The sympathetic nervous system inhibition in the antihypertensive effect of beta-blockers (author's transl)]. The decrease of sympathetic activity by the beta-blocking drug, as demonstrated by the decreased electric activity of the splanchnic nerve and by the decreased urinary catecholamine reponse to tilt as well as by the decreased levels of plasma dopamine beta-hydroxylase exists not only in hypertension with elevated PRA but also in hypertension with normal or low PRA. In these latter cases the antihypertensive effect is better explained by the decrease in the sympathetic nervous system activity than by the decrease of PRA. This effect seems to be indirect and probably, as suggested by Lewis, as a result of damping sensory input to the central nervous system from the heart, whose capacity to respond to exercice and stress is blunted by beta-adreno-receptor blockade."}
{"id": "PMID:23525", "title": "Haemoglobin oxygen dissociation curve in patients on regular haemodialysis.", "content": "Changes in the haemoglobin-oxygen dissociation curve (Hb-O2) and the factors which influence its position were studied before and after dialysis in 7 patients on regular haemodialysis during 20 dialyses. Seven normal subjects were used as controls. Haemoglobin showed a lower than normal affinity for O2 in uraemic patients before haemodialysis (p50in vivo = 33.09 +/- 0.92 mmHg and p507.4 = 31.51 +/- 0.73 mmHg, P less than 0.001), and this could be considered as a protection against tissue anoxia. After dialysis Hb-O2 affinity at the patient's pH (p50 in vivo = 27.97 +/- 0.57 mmHg, P less than 0.001). This probably eliminates the benefits of the predialysis balance of tissue oxygenation, producing a degree of hypoxia, and may play a role in the genesis of post-dialysis symptoms. Measures should be taken to improve oxygenation of high risk patients with latent heart failure or respiratory disturbances during and after dialysis.", "contents": "Haemoglobin oxygen dissociation curve in patients on regular haemodialysis. Changes in the haemoglobin-oxygen dissociation curve (Hb-O2) and the factors which influence its position were studied before and after dialysis in 7 patients on regular haemodialysis during 20 dialyses. Seven normal subjects were used as controls. Haemoglobin showed a lower than normal affinity for O2 in uraemic patients before haemodialysis (p50in vivo = 33.09 +/- 0.92 mmHg and p507.4 = 31.51 +/- 0.73 mmHg, P less than 0.001), and this could be considered as a protection against tissue anoxia. After dialysis Hb-O2 affinity at the patient's pH (p50 in vivo = 27.97 +/- 0.57 mmHg, P less than 0.001). This probably eliminates the benefits of the predialysis balance of tissue oxygenation, producing a degree of hypoxia, and may play a role in the genesis of post-dialysis symptoms. Measures should be taken to improve oxygenation of high risk patients with latent heart failure or respiratory disturbances during and after dialysis."}
{"id": "PMID:23522", "title": "The effect of lesions of raphe nuclei on the cataleptic action of neuroleptics.", "content": "The effect of electrolytic lesions of dorsal raphe nucleus (DRN) and median raphe nucleus (MRN), produced with two methods, was tested on catalepsy produced by spiperone, pimozide and haloperidol. Using two methods of evaluating catalepsy (acc. to Delini-Stula and Morpurgo and to Costall et al.) it has been found that both kinds of MRN lesions increase the catalepsy produced by neuroleptics, with the exception of the action of haloperidol as assayed with the Delini-Stula and Morpurgo method, and pimozide as assayed with the method of Costall et al. A lesion of DRN either slightly antagonized or did not influence the cataleptogenic action of neuroleptics.", "contents": "The effect of lesions of raphe nuclei on the cataleptic action of neuroleptics. The effect of electrolytic lesions of dorsal raphe nucleus (DRN) and median raphe nucleus (MRN), produced with two methods, was tested on catalepsy produced by spiperone, pimozide and haloperidol. Using two methods of evaluating catalepsy (acc. to Delini-Stula and Morpurgo and to Costall et al.) it has been found that both kinds of MRN lesions increase the catalepsy produced by neuroleptics, with the exception of the action of haloperidol as assayed with the Delini-Stula and Morpurgo method, and pimozide as assayed with the method of Costall et al. A lesion of DRN either slightly antagonized or did not influence the cataleptogenic action of neuroleptics."}
{"id": "PMID:23526", "title": "Ionised calcium during haemodialysis.", "content": "In spite of the popularity of high calcium dialysate internationally, most centres in the United Kingdom continue to use a dialysate calcium of 1.5 to 1.6 mmol/L. In eleven patients studied throughout dialysis against such dialysate we conclude that it is sufficient to raise ionised calcium. Patients so treated have little elevation of PTH pre-dialysis and it is further suppressed during dialysis.", "contents": "Ionised calcium during haemodialysis. In spite of the popularity of high calcium dialysate internationally, most centres in the United Kingdom continue to use a dialysate calcium of 1.5 to 1.6 mmol/L. In eleven patients studied throughout dialysis against such dialysate we conclude that it is sufficient to raise ionised calcium. Patients so treated have little elevation of PTH pre-dialysis and it is further suppressed during dialysis."}
{"id": "PMID:23524", "title": "[Nicotinamide coenzymes at the early stages of light induction of carotenogenesis in the Neurospora crassa mycelium].", "content": "Changes in the concentration of NAD+, NADH, NADP+ and NADPH in the mycelium of the NADase free mutant of Neurospora crassa were studied during the latent stage of light induction of carotenogenesis. A 30 minute illumination by visible light brought about a stable decrease in the NADH/NAD+NADH ratio, exerting no effect on the NADPH/NADP+NADPH ratio. At the same time the NADP+/NAD+ ratio increased. These changes occurred only when illumination induced carotenoid accumulation in the N. crassa mycelium.", "contents": "[Nicotinamide coenzymes at the early stages of light induction of carotenogenesis in the Neurospora crassa mycelium]. Changes in the concentration of NAD+, NADH, NADP+ and NADPH in the mycelium of the NADase free mutant of Neurospora crassa were studied during the latent stage of light induction of carotenogenesis. A 30 minute illumination by visible light brought about a stable decrease in the NADH/NAD+NADH ratio, exerting no effect on the NADPH/NADP+NADPH ratio. At the same time the NADP+/NAD+ ratio increased. These changes occurred only when illumination induced carotenoid accumulation in the N. crassa mycelium."}
{"id": "PMID:23527", "title": "Peptic ulceration in kidney transplantation.", "content": "Gastroduodenal ulceration occurred in 45 patients during the post-transplantation period in a series of 500 transplantations of 434 patients. The mortality rate of this complication was high, 42%. Bleeding and perforation were the main problems. These complications occurred frequently during treatment for acute rejection. Present day prophylaxis, which is based on the use of antacids, seems to be inadequate for controlling these complications. Other possibilities for reducing the incidence of gastroduodenal ulceration in transplant patients are discussed. Since increased serum gastrin concentrations are often observed in these patients, prophylactic treatment should be based on preoperative evaluation of gastric secretion and serum gastrin determinations. The new histamine (H2) blocking agents should be evaluated in these patients.", "contents": "Peptic ulceration in kidney transplantation. Gastroduodenal ulceration occurred in 45 patients during the post-transplantation period in a series of 500 transplantations of 434 patients. The mortality rate of this complication was high, 42%. Bleeding and perforation were the main problems. These complications occurred frequently during treatment for acute rejection. Present day prophylaxis, which is based on the use of antacids, seems to be inadequate for controlling these complications. Other possibilities for reducing the incidence of gastroduodenal ulceration in transplant patients are discussed. Since increased serum gastrin concentrations are often observed in these patients, prophylactic treatment should be based on preoperative evaluation of gastric secretion and serum gastrin determinations. The new histamine (H2) blocking agents should be evaluated in these patients."}
{"id": "PMID:23530", "title": "Dependence of the rates of dissolution of the Fe4S4 clusters of Chromatium vinosum high-potential iron protein and ferredoxin on cluster oxidation state.", "content": "The influence of oxidation state on the pH dependence of the dissolution of the Fe(4)S(4) clusters of Chromatium vinosum ferredoxin and high-potential iron protein (HIPIP) has been studied. The first-order rate constants (k(obs)) for dissolution of both the Fe(4)S(4)(S-Cys)(4) (2-) and Fe(4)S(4)(S-Cys)(4) (3-) clusters of the ferredoxin follow the same overall kinetic equation but with differing specific rate and equilibrium constants. The dependence of rate and equilibrium constants upon oxidation state may be rationalized on the basis of the accompanying change in electrostatic affinity of a cluster toward H(+) and HO(-). A more drastic change in the pH dependence of the kinetics of dissolution of the Fe(4)S(4) cluster of the HIPIP accompanies its change in oxidation state. Whereas the values of k(obs) for dissolution of HIPIP containing the Fe(4)S(4)(S-Cys)(4) (2-) cluster are strictly second order to [H(+)] and [HO(-)], the pH dependence for dissolution of the HIPIP Fe(4)S(4)(S-Cys)(4) (1-) cluster indicates a first-order dependence upon [H(+)], a second-order dependence upon [HO(-)], and a spontaneous or water rate. These reactivity differences may be related to changes in cluster charge density. Mechanisms of dissolution involve preequilibrium protonation at acidic pH and preequilibrium ligand exchange at basic pH.", "contents": "Dependence of the rates of dissolution of the Fe4S4 clusters of Chromatium vinosum high-potential iron protein and ferredoxin on cluster oxidation state. The influence of oxidation state on the pH dependence of the dissolution of the Fe(4)S(4) clusters of Chromatium vinosum ferredoxin and high-potential iron protein (HIPIP) has been studied. The first-order rate constants (k(obs)) for dissolution of both the Fe(4)S(4)(S-Cys)(4) (2-) and Fe(4)S(4)(S-Cys)(4) (3-) clusters of the ferredoxin follow the same overall kinetic equation but with differing specific rate and equilibrium constants. The dependence of rate and equilibrium constants upon oxidation state may be rationalized on the basis of the accompanying change in electrostatic affinity of a cluster toward H(+) and HO(-). A more drastic change in the pH dependence of the kinetics of dissolution of the Fe(4)S(4) cluster of the HIPIP accompanies its change in oxidation state. Whereas the values of k(obs) for dissolution of HIPIP containing the Fe(4)S(4)(S-Cys)(4) (2-) cluster are strictly second order to [H(+)] and [HO(-)], the pH dependence for dissolution of the HIPIP Fe(4)S(4)(S-Cys)(4) (1-) cluster indicates a first-order dependence upon [H(+)], a second-order dependence upon [HO(-)], and a spontaneous or water rate. These reactivity differences may be related to changes in cluster charge density. Mechanisms of dissolution involve preequilibrium protonation at acidic pH and preequilibrium ligand exchange at basic pH."}
{"id": "PMID:23531", "title": "Probing of beta-adrenergic receptors by novel fluorescent beta-adrenergic blockers.", "content": "The synthesis of two high-affinity fluorescent beta-adrenergic blockers is described: dl-N(1)-[2-hydroxy-3-(1-naphthyloxy)propyl]-N(2)-(9-acridyl)-1,2-propanediamine (9-aminoacridylpropanolol, 9-AAP) and dl-N-[2-hydroxy-3-(1-naphthyloxy)propyl]-N'-dansylethylenediamine (dansyl analogue of propranolol, DAPN). Both 9-AAP and DAPN inhibit competitively the l-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in turkey erythrocyte membranes without affecting the fluoride-stimulated adenylate cyclase activity. Similarly, 9-AAP and DAPN inhibit in a competitive manner the binding of [(125)I]-iodohydroxybenzylpindolol to these beta-adrenergic receptors. The two fluorescent beta-adrenergic blockers 9-AAP and DAPN probe specifically beta-adrenergic receptors in the central nervous system as well as in other organs when injected into rats. The fluorescence pattern can be monitored by fluorescence microscopy performed on cryostat slices of these organs. The appearance of the characteristic fluorescence pattern can be blocked in a stereospecific fashion by a prior injection of l-propranolol and not by a prior injection of d-propranolol. These compounds therefore offer a powerful means to map beta-adrenergic receptors in vivo. The stereospecific displacement of 9-AAP from the beta-adrenergic receptors of turkey erythrocyte membranes by l-propranolol and by l-epinephrine can be detected in vitro using front-face fluorescence. The potential use of these compounds to probe beta-receptors in vitro and in vivo is discussed.", "contents": "Probing of beta-adrenergic receptors by novel fluorescent beta-adrenergic blockers. The synthesis of two high-affinity fluorescent beta-adrenergic blockers is described: dl-N(1)-[2-hydroxy-3-(1-naphthyloxy)propyl]-N(2)-(9-acridyl)-1,2-propanediamine (9-aminoacridylpropanolol, 9-AAP) and dl-N-[2-hydroxy-3-(1-naphthyloxy)propyl]-N'-dansylethylenediamine (dansyl analogue of propranolol, DAPN). Both 9-AAP and DAPN inhibit competitively the l-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in turkey erythrocyte membranes without affecting the fluoride-stimulated adenylate cyclase activity. Similarly, 9-AAP and DAPN inhibit in a competitive manner the binding of [(125)I]-iodohydroxybenzylpindolol to these beta-adrenergic receptors. The two fluorescent beta-adrenergic blockers 9-AAP and DAPN probe specifically beta-adrenergic receptors in the central nervous system as well as in other organs when injected into rats. The fluorescence pattern can be monitored by fluorescence microscopy performed on cryostat slices of these organs. The appearance of the characteristic fluorescence pattern can be blocked in a stereospecific fashion by a prior injection of l-propranolol and not by a prior injection of d-propranolol. These compounds therefore offer a powerful means to map beta-adrenergic receptors in vivo. The stereospecific displacement of 9-AAP from the beta-adrenergic receptors of turkey erythrocyte membranes by l-propranolol and by l-epinephrine can be detected in vitro using front-face fluorescence. The potential use of these compounds to probe beta-receptors in vitro and in vivo is discussed."}
{"id": "PMID:23532", "title": "Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis.", "content": "Serotonin secretion from human platelets, stimulated either by thrombin or the calcium ionophore A23187, was found to be inhibited by anion transport blocking drugs such as 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), pyridoxal phosphate, probenecid, and suramin. These drugs have previously been shown to inhibit ATP-evoked release of epinephrine from isolated chromaffin granules by blocking chloride uptake and subsequent osmotic lysis. However, in contrast to granule release, platelet secretion was insensitive to chloride and, instead, was dependent on OH-. Platelet release was suppressed by low pH, and inhibition by the transport blocking drugs was competitive only with respect to OH-. Serotonin release from platelets was also suppressed by increasing extracellular osmotic strength, and the relationship between suppression and external osmotic strength was quantitatively similar to that observed in the case of chromaffin granules. We conclude that platelet exocytosis could occur when serotonergic granules are closely juxtaposed to the plasma membrane, thus exposing the granule anion transport site to the more alkaline medium. Secretion of serotonin could occur as a consequence of OH- transport and osmotic lysis of the granule-plasma membrane complex, analogous to the chemiosmotic mechanism of chloride-dependent epinephrine release from isolated chromaffin granules.", "contents": "Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis. Serotonin secretion from human platelets, stimulated either by thrombin or the calcium ionophore A23187, was found to be inhibited by anion transport blocking drugs such as 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), pyridoxal phosphate, probenecid, and suramin. These drugs have previously been shown to inhibit ATP-evoked release of epinephrine from isolated chromaffin granules by blocking chloride uptake and subsequent osmotic lysis. However, in contrast to granule release, platelet secretion was insensitive to chloride and, instead, was dependent on OH-. Platelet release was suppressed by low pH, and inhibition by the transport blocking drugs was competitive only with respect to OH-. Serotonin release from platelets was also suppressed by increasing extracellular osmotic strength, and the relationship between suppression and external osmotic strength was quantitatively similar to that observed in the case of chromaffin granules. We conclude that platelet exocytosis could occur when serotonergic granules are closely juxtaposed to the plasma membrane, thus exposing the granule anion transport site to the more alkaline medium. Secretion of serotonin could occur as a consequence of OH- transport and osmotic lysis of the granule-plasma membrane complex, analogous to the chemiosmotic mechanism of chloride-dependent epinephrine release from isolated chromaffin granules."}
{"id": "PMID:23533", "title": "Experimental evidence for a kinetic and electrochemical memory in enzyme membranes.", "content": "The existence of hysteresis phenomena in artificial enzyme membranes due to the coupling of simple kinetic enzyme properties with diffusion transport processes is reported. The intramembrane pH of a urease coating on the surface of a glass pH electrode exhibits a hysteresis loop when the pH of the bulk solution varies cyclically. The steady-state potential of a urease membrane, as a function of the substrate concentration in the bulk solution, also exhibits a memory effect. The influence of the membrane's history on its overall behavior is visualized by electron microscopy. We interpret the results in terms of a coupling between the enzyme reactions and diffusion processes, without taking into account molecular effects.", "contents": "Experimental evidence for a kinetic and electrochemical memory in enzyme membranes. The existence of hysteresis phenomena in artificial enzyme membranes due to the coupling of simple kinetic enzyme properties with diffusion transport processes is reported. The intramembrane pH of a urease coating on the surface of a glass pH electrode exhibits a hysteresis loop when the pH of the bulk solution varies cyclically. The steady-state potential of a urease membrane, as a function of the substrate concentration in the bulk solution, also exhibits a memory effect. The influence of the membrane's history on its overall behavior is visualized by electron microscopy. We interpret the results in terms of a coupling between the enzyme reactions and diffusion processes, without taking into account molecular effects."}
{"id": "PMID:23534", "title": "Identification of transmembrane bridging proteins in the plasma membrane of cultured mouse L cells.", "content": "Studies were carried out to identify transmembrane bridging proteins in the plasma membrane of mouse L-929 cells. Cells grown in suspension culture were 125I-labeled by lactoperoxidase and allowed to ingest latex particles to produce inside-out membrane phagosome preparations. Phagosomes were isolated and the inner membrane surface was labeled with N-(5'-aminopentyl)-5-dimethylamino-1-naphthalenesulfonamide (dansylcadavarine) by a transglutaminase-catalyzed reaction. The phagosome membrane proteins were solubilized and dansylcadavarine-labeled proteins were isolated by anti-dansyl immunoadsorbent affinity chromatography. Dansylcadavarine-labeled proteins were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography for the presence of 125I-labeled material. By this technique, two iodinated proteins with molecular weights of approximately 50,000 and 80,000 appear to be selectively retained by the anti-dansyl immunoadsorbent, suggesting that these proteins span the plasma membrane.", "contents": "Identification of transmembrane bridging proteins in the plasma membrane of cultured mouse L cells. Studies were carried out to identify transmembrane bridging proteins in the plasma membrane of mouse L-929 cells. Cells grown in suspension culture were 125I-labeled by lactoperoxidase and allowed to ingest latex particles to produce inside-out membrane phagosome preparations. Phagosomes were isolated and the inner membrane surface was labeled with N-(5'-aminopentyl)-5-dimethylamino-1-naphthalenesulfonamide (dansylcadavarine) by a transglutaminase-catalyzed reaction. The phagosome membrane proteins were solubilized and dansylcadavarine-labeled proteins were isolated by anti-dansyl immunoadsorbent affinity chromatography. Dansylcadavarine-labeled proteins were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography for the presence of 125I-labeled material. By this technique, two iodinated proteins with molecular weights of approximately 50,000 and 80,000 appear to be selectively retained by the anti-dansyl immunoadsorbent, suggesting that these proteins span the plasma membrane."}
{"id": "PMID:23535", "title": "A pH-conditional mutant of Escherichia coli.", "content": "Mutants of Escherichia coli have been isolated that are able to grow on lactose at pH 7.0 but not at pH 8.1. One of these mutants was analyzed and shown to map in the Z region of the lactose operon. beta-Galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) activity in toluenized mutant cells at pH 8.0 was one-tenth that at pH 7.0. Enzyme purified to near homogeneity from the pH-conditional mutant similarly exhibited pH-conditional activity under conditions where wild-type enzyme was unaffected over a pH range of 6.0-8.0. The pH-conditional beta-galactosidase was used in vivo as a probe for intracellular pH. We show that an internal pH of approximately 7.8-8.0 is maintained through an external pH range of 5.9-7.8. The phenotype of pH-conditional mutants was defined on medium with lactose as the sole carbon source. Under such conditions the gene product itself, beta-galactosidase, is required to maintain intracellular pH, since such maintenance is clearly energy-dependent. Therefore, we were able to recover a pH-conditional mutant in a cytoplasmic gene product. We predict that with any phenotype independent of energy production, however, pH-sensitive mutants will be recovered only in surface elements.", "contents": "A pH-conditional mutant of Escherichia coli. Mutants of Escherichia coli have been isolated that are able to grow on lactose at pH 7.0 but not at pH 8.1. One of these mutants was analyzed and shown to map in the Z region of the lactose operon. beta-Galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) activity in toluenized mutant cells at pH 8.0 was one-tenth that at pH 7.0. Enzyme purified to near homogeneity from the pH-conditional mutant similarly exhibited pH-conditional activity under conditions where wild-type enzyme was unaffected over a pH range of 6.0-8.0. The pH-conditional beta-galactosidase was used in vivo as a probe for intracellular pH. We show that an internal pH of approximately 7.8-8.0 is maintained through an external pH range of 5.9-7.8. The phenotype of pH-conditional mutants was defined on medium with lactose as the sole carbon source. Under such conditions the gene product itself, beta-galactosidase, is required to maintain intracellular pH, since such maintenance is clearly energy-dependent. Therefore, we were able to recover a pH-conditional mutant in a cytoplasmic gene product. We predict that with any phenotype independent of energy production, however, pH-sensitive mutants will be recovered only in surface elements."}
{"id": "PMID:23536", "title": "Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide.", "content": "D-Lysergic acid diethylamide and D-2-bromolysergic acid diethylamide are competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); E.C. 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase is linked to the histamine H2-receptor. Both D-lysergic acid diethylamide and D-2-bromolysergic acid diethylamide show topological congruency with potent H2-antagonists. D-2-Bromolysergic acid diethylamide is 10 times more potent as an H2-antagonist than cimetidine, which has been the most potent H2-antagonist reported, and D-lysergic acid diethylamide is about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromolysergic acid diethylamide and D-lysergic acid diethylamide.", "contents": "Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide. D-Lysergic acid diethylamide and D-2-bromolysergic acid diethylamide are competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); E.C. 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase is linked to the histamine H2-receptor. Both D-lysergic acid diethylamide and D-2-bromolysergic acid diethylamide show topological congruency with potent H2-antagonists. D-2-Bromolysergic acid diethylamide is 10 times more potent as an H2-antagonist than cimetidine, which has been the most potent H2-antagonist reported, and D-lysergic acid diethylamide is about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromolysergic acid diethylamide and D-lysergic acid diethylamide."}
{"id": "PMID:23537", "title": "Heptadecapeptide gastrin in the vagal nerve.", "content": "Immunoreactive gastrin was present in vagal nerves from cats, dogs, and human beings. The abdominal portion of the vagus contained gastrin in amounts ranging from 16 to 273 pmol/g of nerve tissue (wet weight). The thoracic and cervical portion of the vagi contained only minute amounts of gastrin. Gel chromatography of extracts of human, canine, and feline abdominal vagi monitored by region-specific antisera against heptadecapeptide gastrin and triacontatriapeptide cholecystokinin revealed that the vagal gastrin immunoreactivity predominantly consisted of heptadecapeptide gastrin. In addition, the vagi contained small amounts of the NH2-terminal tridecapeptide gastrin fragment as well as of the putative biosynthetic gastrin precursors, components I and II. No cholecystokinin-like molecules were demonstrable. Immunocytochemical studies demonstrated gastrin-containing nerves in the intestinal wall. The nerves were found to be most numerous in the large and distal small intestine. These findings suggest that heptadecapeptide gastrin may represent a new vagal neurotransmitter.", "contents": "Heptadecapeptide gastrin in the vagal nerve. Immunoreactive gastrin was present in vagal nerves from cats, dogs, and human beings. The abdominal portion of the vagus contained gastrin in amounts ranging from 16 to 273 pmol/g of nerve tissue (wet weight). The thoracic and cervical portion of the vagi contained only minute amounts of gastrin. Gel chromatography of extracts of human, canine, and feline abdominal vagi monitored by region-specific antisera against heptadecapeptide gastrin and triacontatriapeptide cholecystokinin revealed that the vagal gastrin immunoreactivity predominantly consisted of heptadecapeptide gastrin. In addition, the vagi contained small amounts of the NH2-terminal tridecapeptide gastrin fragment as well as of the putative biosynthetic gastrin precursors, components I and II. No cholecystokinin-like molecules were demonstrable. Immunocytochemical studies demonstrated gastrin-containing nerves in the intestinal wall. The nerves were found to be most numerous in the large and distal small intestine. These findings suggest that heptadecapeptide gastrin may represent a new vagal neurotransmitter."}
{"id": "PMID:23566", "title": "Prostaglandin release by slow reacting substance from guinea pig and human lung tissue.", "content": "Slow reacting substance (SRS) injected into the pulmonary artery released prostaglandins E (PGE) and F2alpha (PGF2alpha) and the 15-keto-13, 14-dihydro PG metabolites from non-sensitized and ovalbumin sensitized, isolated, perfused guinea pig lungs. PGs were also released from lungs incubated with SRS. Sensitized lungs released more PGs in both types of preparations. Indomethacin inhibited the effect of SRS. Passively sensitized human lung fragments, in parallel to guinea pig lung, released PGE, PGF2alpha and the metabolites when incubated with SRS or antigen. In in vivo experiments, SRS and arachidonic acid given intravenously increased the airway insufflation pressure in anesthetized quinea pigs. These effects, but not the action of injected PGF2alpha and histamine, were abolished by indomethacin. The results indicate that one of the modes of SRS action is by release of PGs, and are consistent with the hypothesis that PGs are predominantly \"secondary\" mediators (in the temporal sense) of the antigen-antibody reaction.", "contents": "Prostaglandin release by slow reacting substance from guinea pig and human lung tissue. Slow reacting substance (SRS) injected into the pulmonary artery released prostaglandins E (PGE) and F2alpha (PGF2alpha) and the 15-keto-13, 14-dihydro PG metabolites from non-sensitized and ovalbumin sensitized, isolated, perfused guinea pig lungs. PGs were also released from lungs incubated with SRS. Sensitized lungs released more PGs in both types of preparations. Indomethacin inhibited the effect of SRS. Passively sensitized human lung fragments, in parallel to guinea pig lung, released PGE, PGF2alpha and the metabolites when incubated with SRS or antigen. In in vivo experiments, SRS and arachidonic acid given intravenously increased the airway insufflation pressure in anesthetized quinea pigs. These effects, but not the action of injected PGF2alpha and histamine, were abolished by indomethacin. The results indicate that one of the modes of SRS action is by release of PGs, and are consistent with the hypothesis that PGs are predominantly \"secondary\" mediators (in the temporal sense) of the antigen-antibody reaction."}
{"id": "PMID:23564", "title": "Dynamic and structural features of a case of compulsive neurosis as revealed in dreams.", "content": "Several examples of the manifest dreams reported by a patient with a compulsive neurosis are presented. An outstanding feature of the dreams was the sudden shift of the dreamer's self-representation from the role of criminal to the role of policeman. This shift is thought to parallel the oscillation between unconscious instinctual gratification and conscious attempts at reparation which is the main dynamic feature of the compulsive neurosis in waking life. The shift of orientation of the self reflects the operation of early defense mechanisms against the sadistic impulse. It also portrays graphically an early stage in the internalization process which leads ultimately to the creation of the superego. The repetitive nature of the dreams indicated that the patient had become fixated at this particular point in the course of his psychic development. It is interesting to note that like the Rat Man this patient suffered from a chronically undescended testicle. The real defect in the sexual apparatus in both patients may have been a factor which favored regression of the libido from the genital stage to the anal-sadistic stage.", "contents": "Dynamic and structural features of a case of compulsive neurosis as revealed in dreams. Several examples of the manifest dreams reported by a patient with a compulsive neurosis are presented. An outstanding feature of the dreams was the sudden shift of the dreamer's self-representation from the role of criminal to the role of policeman. This shift is thought to parallel the oscillation between unconscious instinctual gratification and conscious attempts at reparation which is the main dynamic feature of the compulsive neurosis in waking life. The shift of orientation of the self reflects the operation of early defense mechanisms against the sadistic impulse. It also portrays graphically an early stage in the internalization process which leads ultimately to the creation of the superego. The repetitive nature of the dreams indicated that the patient had become fixated at this particular point in the course of his psychic development. It is interesting to note that like the Rat Man this patient suffered from a chronically undescended testicle. The real defect in the sexual apparatus in both patients may have been a factor which favored regression of the libido from the genital stage to the anal-sadistic stage."}
{"id": "PMID:23580", "title": "[Mental illness and stress].", "content": "Main purpose of my presentation was to give a review on the effects of the stress-factors on the psyche. This aspect has not been taken into consideration sufficiently yet in theory of stress. I like to stress once more that it is the excessive, too intensive stress reaction which is leading to psychic disturbances as well as functional disturbances. Stress which does not exceed a certain extent has to be considered physiologically: the organism needs it as stimulans to obtain its functions: it could not survive without this stimulans. The situation only becomes risky if the stress factors are causing pathogenous disturbances. This situation has been named \"dis-stress\" by Selye. The best guarantees to avoid \"dis-stress\" as well as psychic stress-disorders are changing of attitude of life, compensation of overstrain by sensible recreational activities, going in for sport, engagement for human and social environmental factors as well as a harmonic family-life and a conception of life in the sense of imperturbability and tolerance.", "contents": "[Mental illness and stress]. Main purpose of my presentation was to give a review on the effects of the stress-factors on the psyche. This aspect has not been taken into consideration sufficiently yet in theory of stress. I like to stress once more that it is the excessive, too intensive stress reaction which is leading to psychic disturbances as well as functional disturbances. Stress which does not exceed a certain extent has to be considered physiologically: the organism needs it as stimulans to obtain its functions: it could not survive without this stimulans. The situation only becomes risky if the stress factors are causing pathogenous disturbances. This situation has been named \"dis-stress\" by Selye. The best guarantees to avoid \"dis-stress\" as well as psychic stress-disorders are changing of attitude of life, compensation of overstrain by sensible recreational activities, going in for sport, engagement for human and social environmental factors as well as a harmonic family-life and a conception of life in the sense of imperturbability and tolerance."}
{"id": "PMID:23588", "title": "Control of extracellular slime accumulation in monokaryons and resultant dikaryons of Schizophyllum commune.", "content": "Extracellular slime accumulation, as alcohol-precipitable material was measured after eight days of growth in glucose-asparagine-salts broth in twenty-two different monokaryons and six resultant dikaryons of Schizophyllum commune. The nutritional control of slime accumulation was also examined in monokaryotic mycelium. Slime occurred after growth in sucrose, glucose, fructose and xylose, with glycerol best. Low inorganic phosphates limited both slime and mycelial growth while limiting MgSO4 decreased growth and enhanced slime. In glucose-asparagine broth, various monokaryons differed widely in slime accumulation, ranging from none (e.g., strain 19) to nearly 800 mg per 100 ml filtrate (strain 1) after eight days growth, followed by a marked decline in slime (eleven days to twenty-one days). Resultant dikaryons all showed less slime accumulation, even when established from two high slime-accumulating monokaryons. In contrast, conditions which arrested dikaryotic fruit-body morphogenesis led to increased slime accumulation.", "contents": "Control of extracellular slime accumulation in monokaryons and resultant dikaryons of Schizophyllum commune. Extracellular slime accumulation, as alcohol-precipitable material was measured after eight days of growth in glucose-asparagine-salts broth in twenty-two different monokaryons and six resultant dikaryons of Schizophyllum commune. The nutritional control of slime accumulation was also examined in monokaryotic mycelium. Slime occurred after growth in sucrose, glucose, fructose and xylose, with glycerol best. Low inorganic phosphates limited both slime and mycelial growth while limiting MgSO4 decreased growth and enhanced slime. In glucose-asparagine broth, various monokaryons differed widely in slime accumulation, ranging from none (e.g., strain 19) to nearly 800 mg per 100 ml filtrate (strain 1) after eight days growth, followed by a marked decline in slime (eleven days to twenty-one days). Resultant dikaryons all showed less slime accumulation, even when established from two high slime-accumulating monokaryons. In contrast, conditions which arrested dikaryotic fruit-body morphogenesis led to increased slime accumulation."}
{"id": "PMID:23589", "title": "Lipolytic enzymes of Trichophyton rubrum.", "content": "Trichophyton rubrum cells contain lipase, phospholipases A and B and acyl CoA lysolecithin acyl transferase activities. This dermatophyte excretes lipase and phospholipase A into the growth medium when cultivated in Sabouraud's broth. Extracellular lipase has optimum activity at pH 8.0 whereas the intracellular lipase is maximally active at pH 8.0 whereas the intracellular lipase is maximally active at pH 7.0. The optimum pH of phospholipase A and B activities which are localized in 15000 g sedimentable cell fragments are 7.0 and 6.0 respectively. Supernatant obtained after removal of 1,005,000 g sedimentable fragments from cell extract contains acyl CoA lysolecithin acyl transferase which requires ATP, CoA, Mg2+ and an unsaturated fatty acid for its activity.", "contents": "Lipolytic enzymes of Trichophyton rubrum. Trichophyton rubrum cells contain lipase, phospholipases A and B and acyl CoA lysolecithin acyl transferase activities. This dermatophyte excretes lipase and phospholipase A into the growth medium when cultivated in Sabouraud's broth. Extracellular lipase has optimum activity at pH 8.0 whereas the intracellular lipase is maximally active at pH 8.0 whereas the intracellular lipase is maximally active at pH 7.0. The optimum pH of phospholipase A and B activities which are localized in 15000 g sedimentable cell fragments are 7.0 and 6.0 respectively. Supernatant obtained after removal of 1,005,000 g sedimentable fragments from cell extract contains acyl CoA lysolecithin acyl transferase which requires ATP, CoA, Mg2+ and an unsaturated fatty acid for its activity."}
{"id": "PMID:23595", "title": "[The prevention of accidents in dental local anesthesia].", "content": "The relatively rare complications developing under local anaesthesia may be due to various causes. The possibilities of the development of accidents under local anaesthesia are outlined; and prophylactic and therapeutic measures are deduced. A schematic premedication cannot prevent the development of complications with a sufficient degree of certainty; for instance, in certain cases the administration of atropine alone will still worsen the course of a complication. On the contrary, an individual premedication should be aimed at, especially in risk patients; the dosage must take into consideration all important factors. Consequently, atropine is of less importance than, for example, psychopharmaca and beta-receptor blockers.", "contents": "[The prevention of accidents in dental local anesthesia]. The relatively rare complications developing under local anaesthesia may be due to various causes. The possibilities of the development of accidents under local anaesthesia are outlined; and prophylactic and therapeutic measures are deduced. A schematic premedication cannot prevent the development of complications with a sufficient degree of certainty; for instance, in certain cases the administration of atropine alone will still worsen the course of a complication. On the contrary, an individual premedication should be aimed at, especially in risk patients; the dosage must take into consideration all important factors. Consequently, atropine is of less importance than, for example, psychopharmaca and beta-receptor blockers."}
{"id": "PMID:23599", "title": "Uric acid calculi: results of conservative treatment.", "content": "A total of 140 patients with uric acid diathesis have been treated for the last five years with a standardized mixture of sodium and potassium citrate and citric acid (Uralyt U) together with forced fluid intake and, if necessary, the addition of allopurinol. The results have been encouraging; 80 per cent of the patients showed complete dissolution of the stones and relief of symptoms.", "contents": "Uric acid calculi: results of conservative treatment. A total of 140 patients with uric acid diathesis have been treated for the last five years with a standardized mixture of sodium and potassium citrate and citric acid (Uralyt U) together with forced fluid intake and, if necessary, the addition of allopurinol. The results have been encouraging; 80 per cent of the patients showed complete dissolution of the stones and relief of symptoms."}
{"id": "PMID:23600", "title": "Endocrine tests in phenotypic children with bilateral impalpable testes can reliably predict \"congenital\" anorchism.", "content": "Congenital anorchism is a rare condition. Bilateral impa-pable undescended testes are relatively common by comparison. Surgical exploration has been regarded as the final arbiter between anorchism and bilateral cryptorchism. Exploration has not proved completely reliable in making this differentiation. Endocrine studies, particularly the human chorionic gonadotropin (HCG) stimulation test together with measurements of basal plasma gonadotropins, can reliably exclude \"functioning\" testicular tissue. Eleven fully evaluated and operated cases support this contention. In the specific clinical setting of a normal phenotypic male child with a 46XY karyotype and no m\u00fcllerian structures palpable on rectal examination, nonfunctioning testes on endocrine testing means congenital anorchism and surgical confirmation is unnecessary. In contradistinction, a positive HCG test would appear to mandate through and extensive surgical exploration.", "contents": "Endocrine tests in phenotypic children with bilateral impalpable testes can reliably predict \"congenital\" anorchism. Congenital anorchism is a rare condition. Bilateral impa-pable undescended testes are relatively common by comparison. Surgical exploration has been regarded as the final arbiter between anorchism and bilateral cryptorchism. Exploration has not proved completely reliable in making this differentiation. Endocrine studies, particularly the human chorionic gonadotropin (HCG) stimulation test together with measurements of basal plasma gonadotropins, can reliably exclude \"functioning\" testicular tissue. Eleven fully evaluated and operated cases support this contention. In the specific clinical setting of a normal phenotypic male child with a 46XY karyotype and no m\u00fcllerian structures palpable on rectal examination, nonfunctioning testes on endocrine testing means congenital anorchism and surgical confirmation is unnecessary. In contradistinction, a positive HCG test would appear to mandate through and extensive surgical exploration."}
{"id": "PMID:23602", "title": "[Acid-base indices in ovine blood and cerebrospinal fluid].", "content": "By means of the Astrup apparatus (Blood Microsystem BMS 2) acid-base indices in blood and cerebro-spinal fluid of clinically healthy Merino sheep at the age of one year (15 head) and of two or three years (41 head) were determined. Blood collected anaerobically from v. jugularis and liquor collected by means of the suboccipital punction in heparinized syringes and/or caplaris and liquor collected by means of the suboccipital punction in heparinized syringes and/or capillaries were examined immediately after the collection. Following indices were obtained and re-counted according to nomograms: actual pH, partial CO2 pressure--pCO2 base excess--BE, base buffer--BB, standard bicarbonate--SB, actual bicarbonate--AB, total CO2--tCO2 (Tables I, II). Indices of pH, pCO2, BE and BB indicated statistically significant differences in values when comparing liquor with venous blood (in younger ewes). As the values of the sheep cerebro-spinal fluid indices examined are not to be found in literature, the above stated values can be recommended to be used as basic values for a given age group.", "contents": "[Acid-base indices in ovine blood and cerebrospinal fluid]. By means of the Astrup apparatus (Blood Microsystem BMS 2) acid-base indices in blood and cerebro-spinal fluid of clinically healthy Merino sheep at the age of one year (15 head) and of two or three years (41 head) were determined. Blood collected anaerobically from v. jugularis and liquor collected by means of the suboccipital punction in heparinized syringes and/or caplaris and liquor collected by means of the suboccipital punction in heparinized syringes and/or capillaries were examined immediately after the collection. Following indices were obtained and re-counted according to nomograms: actual pH, partial CO2 pressure--pCO2 base excess--BE, base buffer--BB, standard bicarbonate--SB, actual bicarbonate--AB, total CO2--tCO2 (Tables I, II). Indices of pH, pCO2, BE and BB indicated statistically significant differences in values when comparing liquor with venous blood (in younger ewes). As the values of the sheep cerebro-spinal fluid indices examined are not to be found in literature, the above stated values can be recommended to be used as basic values for a given age group."}
{"id": "PMID:23608", "title": "[Rat brain and liver glutamine synthetase and gamma-glutamyltransferase activity in alloxan diabetes (IV)].", "content": "Glutamine synthetase and gamma-glutamyltransferase activities of brain and liver homogenates of rats suffering from alloxan diabetes were determined in the soluble fraction (fraction 1) and in that obtained after treatment with 0.2 percent deoxycholate (fraction 2). The results obtained indicate that the activities of these enzymes in homogenates of brain and liver of diabetic animals does not differ from that of normal animals. gamma-Glutamyltransferase activity of brain is significantly reduced (about 5 fold) in the soluble fraction while glutamine synthetase activity is not much changed. The activities of glutamine-synthetase and gamma-glutamyltransferase of the 2-nd fraction obtained from rat brain and liver are very much higher than in the first fraction and are not considerably different from the activities observed in normal animals. In contrast to brain, glutamine synthetase and gamma-glutamyltransferase activities of liver of diabetic animals do not differ from the activities observed in normal animals, both in the homogenates and in the 1-st and 2-nd fractions.", "contents": "[Rat brain and liver glutamine synthetase and gamma-glutamyltransferase activity in alloxan diabetes (IV)]. Glutamine synthetase and gamma-glutamyltransferase activities of brain and liver homogenates of rats suffering from alloxan diabetes were determined in the soluble fraction (fraction 1) and in that obtained after treatment with 0.2 percent deoxycholate (fraction 2). The results obtained indicate that the activities of these enzymes in homogenates of brain and liver of diabetic animals does not differ from that of normal animals. gamma-Glutamyltransferase activity of brain is significantly reduced (about 5 fold) in the soluble fraction while glutamine synthetase activity is not much changed. The activities of glutamine-synthetase and gamma-glutamyltransferase of the 2-nd fraction obtained from rat brain and liver are very much higher than in the first fraction and are not considerably different from the activities observed in normal animals. In contrast to brain, glutamine synthetase and gamma-glutamyltransferase activities of liver of diabetic animals do not differ from the activities observed in normal animals, both in the homogenates and in the 1-st and 2-nd fractions."}
{"id": "PMID:23609", "title": "[Mechanisms regulating citric acid metabolism in the brain].", "content": "The changes in the rates of citrate biosynthesis and utilization in rat brain, liver, kidney and heart, produced by hypoxia, action of 2,4-DNP and thyreotoxicosis, were compared with changes of some regulatory parameters under the same conditions. The comparison of citrate-synthase activities, citrate levels in tissues and 14C-incorporation from different precursors into citric acid permitted us to establish that the biosynthesis of citrate in brain was more intensive than in other tissues studied. The main source of acetyl-CoA for citrate-synthase reaction in brain is the oxidation of pyruvate. The ratio of adenine nucleotides plays an important role in the control of citrate-synthase activity in brain, where the oxaloacetate control is not as significant as in liver. NAD-specific isocitrate dehydrogenase reaction was found to be the dominant pathway for citrate oxidation in brain: more than 60 percent of brain citrate were oxidized by NAD-ICDH, while less than 10 percent of citric acid were utilized by this enzyme in other tissues studied. The existance of an adenine nucleotide control of NAD-ICDH activity in brain may be an additional mechanism for the regulation of the first steps of energy metabolism in brain.", "contents": "[Mechanisms regulating citric acid metabolism in the brain]. The changes in the rates of citrate biosynthesis and utilization in rat brain, liver, kidney and heart, produced by hypoxia, action of 2,4-DNP and thyreotoxicosis, were compared with changes of some regulatory parameters under the same conditions. The comparison of citrate-synthase activities, citrate levels in tissues and 14C-incorporation from different precursors into citric acid permitted us to establish that the biosynthesis of citrate in brain was more intensive than in other tissues studied. The main source of acetyl-CoA for citrate-synthase reaction in brain is the oxidation of pyruvate. The ratio of adenine nucleotides plays an important role in the control of citrate-synthase activity in brain, where the oxaloacetate control is not as significant as in liver. NAD-specific isocitrate dehydrogenase reaction was found to be the dominant pathway for citrate oxidation in brain: more than 60 percent of brain citrate were oxidized by NAD-ICDH, while less than 10 percent of citric acid were utilized by this enzyme in other tissues studied. The existance of an adenine nucleotide control of NAD-ICDH activity in brain may be an additional mechanism for the regulation of the first steps of energy metabolism in brain."}
{"id": "PMID:23612", "title": "Comparative metabolism of benorylate and an equivalent mixture of aspirin and paracetamol in neonate and adult rabbits.", "content": "1. Benorylate was well absorbed in rabbits, but more slowly than an equimolar mixture of aspirin and paracetamol. 2. Benorylate was extensively hydrolysed and converted to the typical metabolites of aspirin and paracetamol by both neonate and mature rabbits. 3. Absorption of either aspirin-paracetamol or benorylate was slower in neonate rabbits than in adult rabbits. 4. The excretion rate in adult rabbits was faster, for both aspirin and paracetamol metabolites, than in neonate rabbits.", "contents": "Comparative metabolism of benorylate and an equivalent mixture of aspirin and paracetamol in neonate and adult rabbits. 1. Benorylate was well absorbed in rabbits, but more slowly than an equimolar mixture of aspirin and paracetamol. 2. Benorylate was extensively hydrolysed and converted to the typical metabolites of aspirin and paracetamol by both neonate and mature rabbits. 3. Absorption of either aspirin-paracetamol or benorylate was slower in neonate rabbits than in adult rabbits. 4. The excretion rate in adult rabbits was faster, for both aspirin and paracetamol metabolites, than in neonate rabbits."}
{"id": "PMID:23611", "title": "Orofacial dyskinesia. Clinical features, mechanisms and drug therapy.", "content": "Orofacial or tardive dyskinesias are involuntary repetitive movements of the mouth and face. In most cases, they occur in older psychotic patients who are in institutions and in whom long-term treatment with antipsychotic drugs of the phenothiazine and butyrophenone groups is being carried out. These dyskinesias are frequent in occurrence and characteristically are irreversible. Several biochemical mechanisms have been proposed as causes, including hypersensitivity or partially deneverated brain dopamine receptors and low affinity of the offending drugs for brain muscarinic cholinergic receptors. Clinical therapy has been attempted primarily with drugs that antagonize dopamine receptors or deplete brain dopamine. The benefits of drug treatment have been variable and lack of consistent improvement has been discouraging. Early recognition of dyskinesia should be attempted, and the dose reduced or the drug omitted at the first sign.", "contents": "Orofacial dyskinesia. Clinical features, mechanisms and drug therapy. Orofacial or tardive dyskinesias are involuntary repetitive movements of the mouth and face. In most cases, they occur in older psychotic patients who are in institutions and in whom long-term treatment with antipsychotic drugs of the phenothiazine and butyrophenone groups is being carried out. These dyskinesias are frequent in occurrence and characteristically are irreversible. Several biochemical mechanisms have been proposed as causes, including hypersensitivity or partially deneverated brain dopamine receptors and low affinity of the offending drugs for brain muscarinic cholinergic receptors. Clinical therapy has been attempted primarily with drugs that antagonize dopamine receptors or deplete brain dopamine. The benefits of drug treatment have been variable and lack of consistent improvement has been discouraging. Early recognition of dyskinesia should be attempted, and the dose reduced or the drug omitted at the first sign."}
{"id": "PMID:23613", "title": "[Metabolic acidosis in chronic renal insufficiency of various etiology].", "content": "The renal acidosis may appear by a decrease of the number of nephrons able to function (decrease of the filtrate of the glomerulum) as well as by a selective alteration of the tubular acidification mechanism. In 66 patients with chronic renal insufficiency of different degrees of severity (32 patients with diabetic glomerulosclerosis, 18 patients with chronic glomerulonephritis and 16 patients with chronic pyelonephritis) studies of the parameters of the acid-base-state and the renal insufficiency were carried out. 53 of these patients had a pathologically changed acid-base-state which was most expressed in patients with chronic pyelonephritis. A characteristic relation between the renal function (creatinine clearance) and the change of the pH-values was observed. The regression curve of the pH-values was descending so that in clearance values below 25 ml/min in nearly all patients a pronounced acidosis was present. This could be proved in the patients with pyelonephritis already when higher clearance values were present. The forms of the development of the metabolic acidosis in chronic renal insufficiency are discussed.", "contents": "[Metabolic acidosis in chronic renal insufficiency of various etiology]. The renal acidosis may appear by a decrease of the number of nephrons able to function (decrease of the filtrate of the glomerulum) as well as by a selective alteration of the tubular acidification mechanism. In 66 patients with chronic renal insufficiency of different degrees of severity (32 patients with diabetic glomerulosclerosis, 18 patients with chronic glomerulonephritis and 16 patients with chronic pyelonephritis) studies of the parameters of the acid-base-state and the renal insufficiency were carried out. 53 of these patients had a pathologically changed acid-base-state which was most expressed in patients with chronic pyelonephritis. A characteristic relation between the renal function (creatinine clearance) and the change of the pH-values was observed. The regression curve of the pH-values was descending so that in clearance values below 25 ml/min in nearly all patients a pronounced acidosis was present. This could be proved in the patients with pyelonephritis already when higher clearance values were present. The forms of the development of the metabolic acidosis in chronic renal insufficiency are discussed."}
{"id": "PMID:23614", "title": "[Use of the 25-point ocular grid plate in quantitative-morphological studies of eutopic and dystopic testes of children].", "content": "From plains histologic preparations of children's testicles the volume of seminiferous tubules and extratubular tissue were calculated by use of the points counting method. In ectopic testicles, the extratubular part is significantly larger than in normally descended testes. The range of the values measured by this method diminishes the higher the total count of test points is. The 25-points-test-net of VEB Carl Zeiss Jena in particular met all requirements for quantitative examinations of the morphology of testicles.", "contents": "[Use of the 25-point ocular grid plate in quantitative-morphological studies of eutopic and dystopic testes of children]. From plains histologic preparations of children's testicles the volume of seminiferous tubules and extratubular tissue were calculated by use of the points counting method. In ectopic testicles, the extratubular part is significantly larger than in normally descended testes. The range of the values measured by this method diminishes the higher the total count of test points is. The 25-points-test-net of VEB Carl Zeiss Jena in particular met all requirements for quantitative examinations of the morphology of testicles."}
{"id": "PMID:23615", "title": "[Consideration of the mesenchyme-reaction in patients with cronical liver-diseases (author's transl)].", "content": "The lysosomal glycosidase N-Acetyl-beta-glucosaminidase (beta-NAG) is involved in the breakdown of connective tissue. The activity of this enzyme was determined in sera and biopsies of liver tissue from patients with chronic diseases of the liver of different aetiology. Elevation of enzyme activity was found to be related to an increase of the mesenchymeraction in the injured liver tissue. No correlation was found between activity of beta-NAG and of GPT, gammaGT and CHE.", "contents": "[Consideration of the mesenchyme-reaction in patients with cronical liver-diseases (author's transl)]. The lysosomal glycosidase N-Acetyl-beta-glucosaminidase (beta-NAG) is involved in the breakdown of connective tissue. The activity of this enzyme was determined in sera and biopsies of liver tissue from patients with chronic diseases of the liver of different aetiology. Elevation of enzyme activity was found to be related to an increase of the mesenchymeraction in the injured liver tissue. No correlation was found between activity of beta-NAG and of GPT, gammaGT and CHE."}
{"id": "PMID:23616", "title": "gamma-Radiolyses of DNA in oxygenated aqueous solution. Structure of an alkali-labile site.", "content": "Erythritol-1-d1 has been isolated from gamma-irradiated aqueous oxygenated solution of DNA after reductions with NaBD4, alkali and phosphatase treatment. It is concluded that this product stems from a D-erythrose 2,4-diphosphate unit in the DNA which is formed via a sequence of reactions following H-abstraction at C-2' by OH radicals.", "contents": "gamma-Radiolyses of DNA in oxygenated aqueous solution. Structure of an alkali-labile site. Erythritol-1-d1 has been isolated from gamma-irradiated aqueous oxygenated solution of DNA after reductions with NaBD4, alkali and phosphatase treatment. It is concluded that this product stems from a D-erythrose 2,4-diphosphate unit in the DNA which is formed via a sequence of reactions following H-abstraction at C-2' by OH radicals."}
{"id": "PMID:23630", "title": "Effect of ligands of ferric hemes on interaction between ferric and ferrous chains in partially oxidized hemoglobin A.", "content": "Normal values of Bohr effect of oxygenation of partially oxidized hemoglobin A with ferrihemes liganded either with H2O and OH or with CN have been found in the range of pH values from 6.8 to 7.6 in 45 micrometer (Fe)-hemoglobin containing 36--38% of ferrihemes. As the changes of oxygen affinity of Hb A induced by changes of pH are due to the modifications of R state, this quaternary conformation is thought to be unchanged in the studied of R state, this quaternary conformation is thought to be unchanged in the studied forms of partially oxidized hemoglobin. It is suggested that interactions between ferric and ferrous hemes leading to the increased affinity of ferrous hemes to oxygen occur in deoxygenated form of partially oxidized hemoglobin. In partially oxidized hemoglobin with ferric hemes liganded with H2O asymmetry of oxygen binding curves has been noted, which is not observed in forms with ferric hemes liganded with OH ot CN. This shows the effect of ligands of ferric hemes on interactions between chains containing ferric and ferrous hemes.", "contents": "Effect of ligands of ferric hemes on interaction between ferric and ferrous chains in partially oxidized hemoglobin A. Normal values of Bohr effect of oxygenation of partially oxidized hemoglobin A with ferrihemes liganded either with H2O and OH or with CN have been found in the range of pH values from 6.8 to 7.6 in 45 micrometer (Fe)-hemoglobin containing 36--38% of ferrihemes. As the changes of oxygen affinity of Hb A induced by changes of pH are due to the modifications of R state, this quaternary conformation is thought to be unchanged in the studied of R state, this quaternary conformation is thought to be unchanged in the studied forms of partially oxidized hemoglobin. It is suggested that interactions between ferric and ferrous hemes leading to the increased affinity of ferrous hemes to oxygen occur in deoxygenated form of partially oxidized hemoglobin. In partially oxidized hemoglobin with ferric hemes liganded with H2O asymmetry of oxygen binding curves has been noted, which is not observed in forms with ferric hemes liganded with OH ot CN. This shows the effect of ligands of ferric hemes on interactions between chains containing ferric and ferrous hemes."}
{"id": "PMID:23631", "title": "[The effect of thyroxine on the 2,3-diphosphoglycerate content of erythrocytes in vivo and in vitro].", "content": "After ending a continous treatment with thyroxine the average dropping of the 2,3 DPG level was 0.4 mumol/ml. T4 decreased on the average by 7.6 microgram/ml. One time application of 1 mg thyroxine p.o. led within 24 hours to an increase of the 2,3 DPG level of -chi = 0.2 mumol/ml, the pH in the erythrocytes increased by 0.02 on the average. Blood incubation with thyroxine added in a concentration of -chi = 24 microgram/100 ml showed no increase of 2,3 DPG, pH and phosphate, while there was a significant acidosis and increase of phosphate in the control blood. The lactate production was significantly lower and glucose consumption was significantly higher in the blood with thyroxine.", "contents": "[The effect of thyroxine on the 2,3-diphosphoglycerate content of erythrocytes in vivo and in vitro]. After ending a continous treatment with thyroxine the average dropping of the 2,3 DPG level was 0.4 mumol/ml. T4 decreased on the average by 7.6 microgram/ml. One time application of 1 mg thyroxine p.o. led within 24 hours to an increase of the 2,3 DPG level of -chi = 0.2 mumol/ml, the pH in the erythrocytes increased by 0.02 on the average. Blood incubation with thyroxine added in a concentration of -chi = 24 microgram/100 ml showed no increase of 2,3 DPG, pH and phosphate, while there was a significant acidosis and increase of phosphate in the control blood. The lactate production was significantly lower and glucose consumption was significantly higher in the blood with thyroxine."}
{"id": "PMID:23634", "title": "Characteristics of a new abnormal variant of G-6-PD in human red cells.", "content": "Kinetic and electrophoretic properties were studied in 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G-6-PD) from red cells of donors and patients with hemolytic anemia induced by G-6-PD deficiency. In abnormal variant of G-6-PD isolated from red cells of a patient with hemolytic anemia which had not before been described in the literature was found. The abnormal variant differs from the normal enzyme by a decreased Michaelis constant for G-6-P and NADP, by increased utilization of substrate-analogues (2-deoxy-G-6-P and deamino NADP in particular), by low heat stability, the character of pH dependence, and by the appearance of one band of G-6-PD activity during electrophoresis in polyacrylamide gel. The isolated abnormal variant of G-6-PD has been called \"Kremenchug\" according to the origin of the patient.", "contents": "Characteristics of a new abnormal variant of G-6-PD in human red cells. Kinetic and electrophoretic properties were studied in 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G-6-PD) from red cells of donors and patients with hemolytic anemia induced by G-6-PD deficiency. In abnormal variant of G-6-PD isolated from red cells of a patient with hemolytic anemia which had not before been described in the literature was found. The abnormal variant differs from the normal enzyme by a decreased Michaelis constant for G-6-P and NADP, by increased utilization of substrate-analogues (2-deoxy-G-6-P and deamino NADP in particular), by low heat stability, the character of pH dependence, and by the appearance of one band of G-6-PD activity during electrophoresis in polyacrylamide gel. The isolated abnormal variant of G-6-PD has been called \"Kremenchug\" according to the origin of the patient."}
{"id": "PMID:23635", "title": "Regulation of NAD and NADP synthesis in human red cell.", "content": "NAD is synthesized in red cell from nicotinic acid and PRPP through the formation of nicotinate mononucleotide and desamido-NAD. Synthesis of one mole of NAD requires two moles of ATP. NADP comes from NAD phosphorylation by NAD-kinase (EC.2.7.1.23). NAD and NADP analysis on a population with ATP level ranging from 800 to 2500 nmoles/ml red cells showed a close correlation between ATP and pyridine cofactors. Moreover, NADP level appeared to be dependent of the redox-state of NADP/NADPH couple. Subjects with low NADPH (G-6-PD) deficient red cells, Hb K\u00f6ln) showed lower NADtot/NADPtot ratio, suggesting a NAD-kinase equilibrium shift toward NADP related to lower levels of the negative effector NADPH, as already described in rat liver.", "contents": "Regulation of NAD and NADP synthesis in human red cell. NAD is synthesized in red cell from nicotinic acid and PRPP through the formation of nicotinate mononucleotide and desamido-NAD. Synthesis of one mole of NAD requires two moles of ATP. NADP comes from NAD phosphorylation by NAD-kinase (EC.2.7.1.23). NAD and NADP analysis on a population with ATP level ranging from 800 to 2500 nmoles/ml red cells showed a close correlation between ATP and pyridine cofactors. Moreover, NADP level appeared to be dependent of the redox-state of NADP/NADPH couple. Subjects with low NADPH (G-6-PD) deficient red cells, Hb K\u00f6ln) showed lower NADtot/NADPtot ratio, suggesting a NAD-kinase equilibrium shift toward NADP related to lower levels of the negative effector NADPH, as already described in rat liver."}
{"id": "PMID:23636", "title": "[Glucose-6-phosphate dehydrogenase deficiency of erythrocytes in the GDR].", "content": "34 persons with G-6-PD deficiency were diagnosed, and the pathological enzyme-variants of red blood cells were characterized according to the recommendations of WHO. We conclude from the differing residual G-6-PD-activities in red blood cells of the propositi and the differing reactivity of the enzyme in kinetic and physicochemical characterizations that a multiple variety of rare pathological G-6-PD variants exists in the GDR. Using the estimated enzymeparameters it was not possible in all cases to compare directly the newly demonstrated G-6-PD variants with cases already described in the literature. In addition, the differing combinations of parameters render a classification more difficult.", "contents": "[Glucose-6-phosphate dehydrogenase deficiency of erythrocytes in the GDR]. 34 persons with G-6-PD deficiency were diagnosed, and the pathological enzyme-variants of red blood cells were characterized according to the recommendations of WHO. We conclude from the differing residual G-6-PD-activities in red blood cells of the propositi and the differing reactivity of the enzyme in kinetic and physicochemical characterizations that a multiple variety of rare pathological G-6-PD variants exists in the GDR. Using the estimated enzymeparameters it was not possible in all cases to compare directly the newly demonstrated G-6-PD variants with cases already described in the literature. In addition, the differing combinations of parameters render a classification more difficult."}
{"id": "PMID:23637", "title": "[Detection of female heterozygous glucose-6-phosphate dehydrogenase deficiency].", "content": "Diagnostics of heterozygotes are required for population studies, for the detection and consultation of persons with G-6-PD deficiency prone to hemolysis. The diagnostics of heterozygous females with the corresponding trait are problematic in families without hemizygous patients. 1. The determination of the activity is only applicable to the differentiation between heterozygotes and homozygotes if the activities are below the reference range. Heterozygous G-6-PD deficiency with normal activity cannot be identified by this method. 2. Existence of G-6-PD defects is demonstrated by mosaicism even in case of normactivity (T\u00f6nztest). 3. Incubation with and without NADP of stroma-free hemolysates involving heat labile enzyme mutants results in a marked decrease of activity within 20 min at 46 degrees C. 4. Electrophoresis on Cellogel demonstrates changes of charge in the mutated enzyme. 5. Family examination verifies suspicion of the heterozygous trait. A combination of parameters is recommended to obtain an improvement in the detection of persons with the heterozygous trait.", "contents": "[Detection of female heterozygous glucose-6-phosphate dehydrogenase deficiency]. Diagnostics of heterozygotes are required for population studies, for the detection and consultation of persons with G-6-PD deficiency prone to hemolysis. The diagnostics of heterozygous females with the corresponding trait are problematic in families without hemizygous patients. 1. The determination of the activity is only applicable to the differentiation between heterozygotes and homozygotes if the activities are below the reference range. Heterozygous G-6-PD deficiency with normal activity cannot be identified by this method. 2. Existence of G-6-PD defects is demonstrated by mosaicism even in case of normactivity (T\u00f6nztest). 3. Incubation with and without NADP of stroma-free hemolysates involving heat labile enzyme mutants results in a marked decrease of activity within 20 min at 46 degrees C. 4. Electrophoresis on Cellogel demonstrates changes of charge in the mutated enzyme. 5. Family examination verifies suspicion of the heterozygous trait. A combination of parameters is recommended to obtain an improvement in the detection of persons with the heterozygous trait."}
{"id": "PMID:23638", "title": "Mechanism of senescence of red blood cells.", "content": "An integral hypothesis is submitted on the interaction of endogenous and exogenous factors in the mechanism of senescence of erythrocytes and on their selective phagocytosis by autologous macrophages. A method that allows quantitative determination and preparative yield of senescent erythrocytes is proposed.", "contents": "Mechanism of senescence of red blood cells. An integral hypothesis is submitted on the interaction of endogenous and exogenous factors in the mechanism of senescence of erythrocytes and on their selective phagocytosis by autologous macrophages. A method that allows quantitative determination and preparative yield of senescent erythrocytes is proposed."}
{"id": "PMID:23642", "title": "[Sedimentation rate of erythrocytes as an indicator for phase transitions in the membrane].", "content": "Temperature dependent sedimentation measurements with human erythrocytes showed that the sedimentation velocity at 21 degrees C in Krebs-Ringer-solution, pH 7.4, has a peak shaped minimum [1]. In further investigations it could be shown that a phase transition of membrane lipids is the main reason of this peak. Membrane proteins influence the sedimentation behavior of the erythrocytes only by changing the interaction with membrane lipids.", "contents": "[Sedimentation rate of erythrocytes as an indicator for phase transitions in the membrane]. Temperature dependent sedimentation measurements with human erythrocytes showed that the sedimentation velocity at 21 degrees C in Krebs-Ringer-solution, pH 7.4, has a peak shaped minimum [1]. In further investigations it could be shown that a phase transition of membrane lipids is the main reason of this peak. Membrane proteins influence the sedimentation behavior of the erythrocytes only by changing the interaction with membrane lipids."}
{"id": "PMID:23644", "title": "Serum gamma-glutamyl transpeptidase: its clinical significance.", "content": "Serum gamma-glutamyl transpeptidase (gamma-GT) level was estimated in 132 patients with different liver diseases (chronic persistent and chronic active hepatitis, postnecrotic cirrhosis, chronic alcholic hepatitis and alcoholic cirrhosis, cholestasis syndrome, fatty liver, Gilbert disease) and malignancies with and without liver involvement. The gamma-GT levels were compared with the values for serum bilirubin, transaminases (GOT, GPT) and alkaline phosphatase in the same patients. gamma-GT values were normal in chronic persistent hepatitis and increased in chronic active hepatitis. Very high activities were measured in chronic alcoholic cirrhosis in contrast to postnecrotic cirrhosis. gamma-GT proved to be more sensitive than alkaline phosphate as an index of cholestasis and liver involvement in malignancies. It is suggested that gamma-GT activity offers valuable aid in differential diagnostics of liver-diseases. gamma-GT being an inducible enzyme, its activity may be raised by enzyme inducing drugs also in subjects without liver disease.", "contents": "Serum gamma-glutamyl transpeptidase: its clinical significance. Serum gamma-glutamyl transpeptidase (gamma-GT) level was estimated in 132 patients with different liver diseases (chronic persistent and chronic active hepatitis, postnecrotic cirrhosis, chronic alcholic hepatitis and alcoholic cirrhosis, cholestasis syndrome, fatty liver, Gilbert disease) and malignancies with and without liver involvement. The gamma-GT levels were compared with the values for serum bilirubin, transaminases (GOT, GPT) and alkaline phosphatase in the same patients. gamma-GT values were normal in chronic persistent hepatitis and increased in chronic active hepatitis. Very high activities were measured in chronic alcoholic cirrhosis in contrast to postnecrotic cirrhosis. gamma-GT proved to be more sensitive than alkaline phosphate as an index of cholestasis and liver involvement in malignancies. It is suggested that gamma-GT activity offers valuable aid in differential diagnostics of liver-diseases. gamma-GT being an inducible enzyme, its activity may be raised by enzyme inducing drugs also in subjects without liver disease."}
{"id": "PMID:23645", "title": "[Painful ophthalmoplegia (author's transl)].", "content": "The authors begin by enumerating the various syndromes in which painful ophthalmoplegia may be observed (sphenoidal fissure syndrome, Collier's syndrome, syndromes involving the orbital apex, the cavernous sinus and parasellar syndromes; Raeder's syndrome, Gradenigo's syndrome and Fischer-Brugge syndrome). They then discuss the various causes that must be investigated in all cases of painful ophtalmoplegia. They consider in order: -- ophtalmoplegia due to general causes (especially diabetes) and neurological causes (e.g. multiple sclerosis); -- ophtalmoplegia due to common local canses space-occupying processes, vascular malformations, ear, nose and larynx infections); -- painful ophalmoplegia of unknown origin, which includes four entities of very differing importance (Gubler and Charcot's ophthalmoplegic migraine and Tolosa-Hunt syndrome of which the clinical symptoms and course are so different that they can be distinguished as two entities; and, secondarily, inflammatory pseudo-tumours of the orbit and the recurrent multiple cranial nerve palsies that are observed in South-East Asia).  (Acta nurol. belg., 1977, 77, 331-350).", "contents": "[Painful ophthalmoplegia (author's transl)]. The authors begin by enumerating the various syndromes in which painful ophthalmoplegia may be observed (sphenoidal fissure syndrome, Collier's syndrome, syndromes involving the orbital apex, the cavernous sinus and parasellar syndromes; Raeder's syndrome, Gradenigo's syndrome and Fischer-Brugge syndrome). They then discuss the various causes that must be investigated in all cases of painful ophtalmoplegia. They consider in order: -- ophtalmoplegia due to general causes (especially diabetes) and neurological causes (e.g. multiple sclerosis); -- ophtalmoplegia due to common local canses space-occupying processes, vascular malformations, ear, nose and larynx infections); -- painful ophalmoplegia of unknown origin, which includes four entities of very differing importance (Gubler and Charcot's ophthalmoplegic migraine and Tolosa-Hunt syndrome of which the clinical symptoms and course are so different that they can be distinguished as two entities; and, secondarily, inflammatory pseudo-tumours of the orbit and the recurrent multiple cranial nerve palsies that are observed in South-East Asia).  (Acta nurol. belg., 1977, 77, 331-350)."}
{"id": "PMID:23648", "title": "Naphthylamidase used as a lysosome marker in the study of acute selective necrosis of the internal granular layer of cerebellum.", "content": "Histochemical examination of the activity of naphthylamidase (LNAse) in the cerebellar cortex of 70 human autopsies consistantly revealed a marked activity mainly in the internal granular layer with pH optimum of 5.8. Slight enzyme activity was also localized in sites corresponding to lipofuscin deposits and areas of acid phosphatase activity in the Bergmann glial cells, Purkinje cells and in perivascular cells. The histochemical findings support the LNAse reaction as a lysosome marker. Differences in localization of LNAse and acid phosphatase could possibly be due to prior release of the latter enzyme from the internal granular layer. Significant correlation between demonstrable loss of granule cell nuclei (the so-called acute, selective necrosis of the granular layer) and low pH of the cerebellar tissue could be demonstrated in 21 cases. The present findings support the hypothesis that an enzymatic disintegration of the granule cells takes place in postmortem cerebella with low pH simulating a necrotic vital phenomenon.", "contents": "Naphthylamidase used as a lysosome marker in the study of acute selective necrosis of the internal granular layer of cerebellum. Histochemical examination of the activity of naphthylamidase (LNAse) in the cerebellar cortex of 70 human autopsies consistantly revealed a marked activity mainly in the internal granular layer with pH optimum of 5.8. Slight enzyme activity was also localized in sites corresponding to lipofuscin deposits and areas of acid phosphatase activity in the Bergmann glial cells, Purkinje cells and in perivascular cells. The histochemical findings support the LNAse reaction as a lysosome marker. Differences in localization of LNAse and acid phosphatase could possibly be due to prior release of the latter enzyme from the internal granular layer. Significant correlation between demonstrable loss of granule cell nuclei (the so-called acute, selective necrosis of the granular layer) and low pH of the cerebellar tissue could be demonstrated in 21 cases. The present findings support the hypothesis that an enzymatic disintegration of the granule cells takes place in postmortem cerebella with low pH simulating a necrotic vital phenomenon."}
{"id": "PMID:23649", "title": "Surface-charge characteristics of smooth and rough Salmonella typhimurium bacteria determined by aqueous two-phase partitioning and free zones electrophoresis.", "content": "Aqueous biphasic partitioning of Salmonella typhimurium S and R bacteria in a system containing 6.2 per cent (w/w) dextran 500 and 4.4 per cent (w/w) poly(ethyleneglycol) 6000 (PEG) was similar to the partition of the corresponding surface lipopolysaccharide (LPS). Further partition analysis with charged PEG showed that S bacteria and their LPS exposed very little charge, whereas R bacteria and their LPS showed a conspicuous negative charge at neutral pH. Free zone electrophoresis also indicated that the S bacteria have a much lower surface charge density than the R bacteria and accordingly a different surface structure. Thus, the physico-chemical properties of the bacterial surface seem to be determined to a great extent by the characteristics of the cell surface LPS.", "contents": "Surface-charge characteristics of smooth and rough Salmonella typhimurium bacteria determined by aqueous two-phase partitioning and free zones electrophoresis. Aqueous biphasic partitioning of Salmonella typhimurium S and R bacteria in a system containing 6.2 per cent (w/w) dextran 500 and 4.4 per cent (w/w) poly(ethyleneglycol) 6000 (PEG) was similar to the partition of the corresponding surface lipopolysaccharide (LPS). Further partition analysis with charged PEG showed that S bacteria and their LPS exposed very little charge, whereas R bacteria and their LPS showed a conspicuous negative charge at neutral pH. Free zone electrophoresis also indicated that the S bacteria have a much lower surface charge density than the R bacteria and accordingly a different surface structure. Thus, the physico-chemical properties of the bacterial surface seem to be determined to a great extent by the characteristics of the cell surface LPS."}
{"id": "PMID:23650", "title": "Physiological and pathophysiological aspects of gastrointestinal peptide hormones.", "content": "The author made a review about the origin, the biochemistry the physiological and pathological roles of gastrointestinal peptide hormones. They originate from the APUD cell system, chemically from the ancient growth hormone, or placental lactogen. The theoretical prosecgastrin's first sequencies form the \"secretin family\", the tail sequencies form the \"gastrin family\". The author describes many details of their effects on the different gastrointestinal organs, they behave mainly antagonistic way to each other. Finally a discussions is given about their role in the development of peptic ulcer, in the WDHA syndrome and in malabsorption.", "contents": "Physiological and pathophysiological aspects of gastrointestinal peptide hormones. The author made a review about the origin, the biochemistry the physiological and pathological roles of gastrointestinal peptide hormones. They originate from the APUD cell system, chemically from the ancient growth hormone, or placental lactogen. The theoretical prosecgastrin's first sequencies form the \"secretin family\", the tail sequencies form the \"gastrin family\". The author describes many details of their effects on the different gastrointestinal organs, they behave mainly antagonistic way to each other. Finally a discussions is given about their role in the development of peptic ulcer, in the WDHA syndrome and in malabsorption."}
{"id": "PMID:23654", "title": "Maintenance of Glossina palpalis fed through bat's wing membrane on defibrinated blood.", "content": "Teneral laboratory-bred Glossina palpalis flies were successfully fed through bat's wing membrane on defibrinated blood by means of a technique developed in this laboratory. Using this technique almost 100% of the flies engorged blood through the membrane. Ten to fifteen flies were kept in Standard 'Geigy 10' or 'Geigy 15' cages and records were kept of mortality and the weights of the pupae produced; over 78% of the flies were still after 60 days of the experiment. Over 75% of the membrane-fed G. palpalis females produced pupae in the first 30 days of the females' reproductive life. The mean weight of the pupae produced by the membrane-fed flies was 24.9 mg. The results indicate that membranes made from the African fruit bat wings are usable, and that this type of membrane would be valuable for a medium scale rearing programme for tsetse flies.", "contents": "Maintenance of Glossina palpalis fed through bat's wing membrane on defibrinated blood. Teneral laboratory-bred Glossina palpalis flies were successfully fed through bat's wing membrane on defibrinated blood by means of a technique developed in this laboratory. Using this technique almost 100% of the flies engorged blood through the membrane. Ten to fifteen flies were kept in Standard 'Geigy 10' or 'Geigy 15' cages and records were kept of mortality and the weights of the pupae produced; over 78% of the flies were still after 60 days of the experiment. Over 75% of the membrane-fed G. palpalis females produced pupae in the first 30 days of the females' reproductive life. The mean weight of the pupae produced by the membrane-fed flies was 24.9 mg. The results indicate that membranes made from the African fruit bat wings are usable, and that this type of membrane would be valuable for a medium scale rearing programme for tsetse flies."}
{"id": "PMID:23655", "title": "[The etiology of sylvatic trichinellosis in Switzerland].", "content": "Three Trichinella strains from Swiss wild foxes (Vulpes vulpes) were tested in crossbreeding experiments with Trichinella spiralis, T. nativa and T. nelsoni using white mice as laboratory animals. The results demonstrated that T. nelsoni Britov et Boev 1972 is the etiologic agent of sylvatic trichinellosis in Switzerland. Former isolations of these species were successful in materials from East and South Africa, USSR (Republics of Tadzhikistan, Turkmenia and Kazakhstan) and Bulgaria. The area of T. nelsoni covers probably the whole southern part of the Old World up to the 48th degree of northern latitude.", "contents": "[The etiology of sylvatic trichinellosis in Switzerland]. Three Trichinella strains from Swiss wild foxes (Vulpes vulpes) were tested in crossbreeding experiments with Trichinella spiralis, T. nativa and T. nelsoni using white mice as laboratory animals. The results demonstrated that T. nelsoni Britov et Boev 1972 is the etiologic agent of sylvatic trichinellosis in Switzerland. Former isolations of these species were successful in materials from East and South Africa, USSR (Republics of Tadzhikistan, Turkmenia and Kazakhstan) and Bulgaria. The area of T. nelsoni covers probably the whole southern part of the Old World up to the 48th degree of northern latitude."}
{"id": "PMID:23657", "title": "[Mycetoma in Somalia - results of a survey done from 1959 to 1964].", "content": "The Pasteur Institute studied 103 mycetoma patients in Somalia between 1959 and 1964. Grains were seen in 94 of them and this, added to cultural features, allowed the diagnosis of 60 pathogens as follows: 44 Madurella mycetomi, 1 Leptosphaeria senegalensis, 7 Pyrenochaeta romeroi (or Madurella grisea), 3 Allescheria boydii, 1 Fusarium sp., 3 Neotestudina (Zopfia) rosatii, and 1 unidentified; 34 were actinomycetes: 24 Streptomyces somaliensis, 4 Actinomadura madurae, 3 A. pelletieri and 3 Nocardia spp. The patients delayed too long in consulting their doctors and health education is vital if amputations are to be avoided. The geographical distribution is related to climate and fungal species. In central Somalia the association of M. mycetomi and S. somaliensis, organisms characteristic of desert conditions, was found; white grain mycetomata and those caused by Nocardia spp. occurred in more humid areas. The study revealed 2 new fungi. One, obtained in culture was called Neotestudina (Zopfia) rosatii. The 3 patients affected, lived in Mudugh (2 in El Bur). The other fungus was not identified. It also was recovered from El Bur and one with similar microscopic characters  has been seen in Chad and also in \"territoire fran\u00e7ais des Afars et des Issas\". Both fungi are desert species.", "contents": "[Mycetoma in Somalia - results of a survey done from 1959 to 1964]. The Pasteur Institute studied 103 mycetoma patients in Somalia between 1959 and 1964. Grains were seen in 94 of them and this, added to cultural features, allowed the diagnosis of 60 pathogens as follows: 44 Madurella mycetomi, 1 Leptosphaeria senegalensis, 7 Pyrenochaeta romeroi (or Madurella grisea), 3 Allescheria boydii, 1 Fusarium sp., 3 Neotestudina (Zopfia) rosatii, and 1 unidentified; 34 were actinomycetes: 24 Streptomyces somaliensis, 4 Actinomadura madurae, 3 A. pelletieri and 3 Nocardia spp. The patients delayed too long in consulting their doctors and health education is vital if amputations are to be avoided. The geographical distribution is related to climate and fungal species. In central Somalia the association of M. mycetomi and S. somaliensis, organisms characteristic of desert conditions, was found; white grain mycetomata and those caused by Nocardia spp. occurred in more humid areas. The study revealed 2 new fungi. One, obtained in culture was called Neotestudina (Zopfia) rosatii. The 3 patients affected, lived in Mudugh (2 in El Bur). The other fungus was not identified. It also was recovered from El Bur and one with similar microscopic characters  has been seen in Chad and also in \"territoire fran\u00e7ais des Afars et des Issas\". Both fungi are desert species."}
{"id": "PMID:23658", "title": "[Tropical entomophthoromycoses].", "content": "A review was made about human entomophthoromycosis observed in tropical areas due to fungi of the order Entomophthorales. Rhinophycomycosis is caused by Entomophthora coronata, a cosmopolitan fungus which is only pathogen in wet tropical and subtropical climates. The disease, a muco-cutaneous infection of the face, induces monstruous deformations. Basidiobolomycosis is caused by Basidiobolus meristosporus, a saprophyte of different amphibians and reptiles very often present in the family Agamidae. The disease interests the subcutaneous tissues and is mainly located at the trunk, shoulders and upper part of the limbs. The epidemiology, clinic and therapeutic were reported. Histopathological lesions and morphology of both fungi were studied. The etiology of the casual agents of these mycoses was discussed.", "contents": "[Tropical entomophthoromycoses]. A review was made about human entomophthoromycosis observed in tropical areas due to fungi of the order Entomophthorales. Rhinophycomycosis is caused by Entomophthora coronata, a cosmopolitan fungus which is only pathogen in wet tropical and subtropical climates. The disease, a muco-cutaneous infection of the face, induces monstruous deformations. Basidiobolomycosis is caused by Basidiobolus meristosporus, a saprophyte of different amphibians and reptiles very often present in the family Agamidae. The disease interests the subcutaneous tissues and is mainly located at the trunk, shoulders and upper part of the limbs. The epidemiology, clinic and therapeutic were reported. Histopathological lesions and morphology of both fungi were studied. The etiology of the casual agents of these mycoses was discussed."}
{"id": "PMID:23659", "title": "Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency.", "content": "Seven urinary metabolites of tryptophan-kynurenine pathway were measured in riboflavin-deficient, pyridoxine-deficient, pair-fed and natural diet baboons. The most significant changes in the pyridoxine-deficient baboons was a mean sevenfold increase in the excretion of xanthurenic acid and a threefold decrease in 3-hydroxy anthranilic acid. The riboflavin-deficient baboons showed a twelvefold increase in the excretion of anthranilic acid, and a tenfold decrease in 3-hydroxy kynurenine. Red blood-cell pyridine nucleotides decreased only in the pyridoxine-deficient baboons, while plasma 11-hydroxy corticosteroids increased only in the riboflavin-deficient baboons. These results are discussed in relation to enzymatic changes that may be expected during these deficiencies.", "contents": "Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. Seven urinary metabolites of tryptophan-kynurenine pathway were measured in riboflavin-deficient, pyridoxine-deficient, pair-fed and natural diet baboons. The most significant changes in the pyridoxine-deficient baboons was a mean sevenfold increase in the excretion of xanthurenic acid and a threefold decrease in 3-hydroxy anthranilic acid. The riboflavin-deficient baboons showed a twelvefold increase in the excretion of anthranilic acid, and a tenfold decrease in 3-hydroxy kynurenine. Red blood-cell pyridine nucleotides decreased only in the pyridoxine-deficient baboons, while plasma 11-hydroxy corticosteroids increased only in the riboflavin-deficient baboons. These results are discussed in relation to enzymatic changes that may be expected during these deficiencies."}
{"id": "PMID:23660", "title": "On the determination of free L-tryptophan.", "content": "The determination of free L-tryptophan depends on several analytical well checked points e.g. absorbing effects, pH of the serum, dependence of the throughput, concentration dependence of retention, volume ultrafiltrated, cut-off, temperature dependence of the binding rate, purification on ion-exchange column, interfering substances of the fluorometric method. Ultrafiltration was compared to an ultracentrifugation technique. In normal human serum the concentration of free L-tryptophan is 3,1 +/- 0,6 microgram/ml and of the bound plus free form 12,2 +/- 1,12 microgram/ml. Both values are dependent on the albumin concentration.", "contents": "On the determination of free L-tryptophan. The determination of free L-tryptophan depends on several analytical well checked points e.g. absorbing effects, pH of the serum, dependence of the throughput, concentration dependence of retention, volume ultrafiltrated, cut-off, temperature dependence of the binding rate, purification on ion-exchange column, interfering substances of the fluorometric method. Ultrafiltration was compared to an ultracentrifugation technique. In normal human serum the concentration of free L-tryptophan is 3,1 +/- 0,6 microgram/ml and of the bound plus free form 12,2 +/- 1,12 microgram/ml. Both values are dependent on the albumin concentration."}
{"id": "PMID:23661", "title": "Studies on the function of tryptophan-108 on lysozyme.", "content": "Chemical studies of selective modification of Trp-108 of lysozyme gave ambiguous results concerning its function on the catalytic activity, since the oxyndole derivative obtained with N-bromosuccinimide is inactive, whereas the kynurenine derivative obtained by oxidation with ozone is fully active. In order to explain this discrepancy, lysozyme has been modified with 2-nitro-4-carboxyphenylsulfenyl chloride (NCPS-Cl). This reagent reacts with the indole ring of tryptophan giving a 2-thioaryl-derivative. By chromatographic fractionation of the reaction mixture, a lysozyme derivative was isolated, that by sequence studies was proved to be modified only at Trp-108 retaining 10% of the lytic activity. Physico-chemical as well as kinetic studies indicate that the large decrease in activity following modification could be related to minor effects in the microenvironment of the active site, with a concomitant modification of the ionization constants of the groups involved in catalysis.", "contents": "Studies on the function of tryptophan-108 on lysozyme. Chemical studies of selective modification of Trp-108 of lysozyme gave ambiguous results concerning its function on the catalytic activity, since the oxyndole derivative obtained with N-bromosuccinimide is inactive, whereas the kynurenine derivative obtained by oxidation with ozone is fully active. In order to explain this discrepancy, lysozyme has been modified with 2-nitro-4-carboxyphenylsulfenyl chloride (NCPS-Cl). This reagent reacts with the indole ring of tryptophan giving a 2-thioaryl-derivative. By chromatographic fractionation of the reaction mixture, a lysozyme derivative was isolated, that by sequence studies was proved to be modified only at Trp-108 retaining 10% of the lytic activity. Physico-chemical as well as kinetic studies indicate that the large decrease in activity following modification could be related to minor effects in the microenvironment of the active site, with a concomitant modification of the ionization constants of the groups involved in catalysis."}
{"id": "PMID:23662", "title": "T antigen synthesis and resistance to interferon in human adenovirus type 12 infected chick cells.", "content": "Tye specific T antigen formation has been demonstrated in primary and secondary chick embryo cells (CEC) infected with adenovirus type 12. The frequency of cells synthesizing T antigen was closely dependent on the multiplicity of infection (MOI). At a MOI of 2.85 TCD50 per cell, T antigen was formed in 50% of cells. Cycloheximide inhibited T antigen formation while cytosine arabinoside had no such effect. CEC infected with adenovirus 12 produced interferon and T antigen, both appearing early and at about the same time of infection Exogenous chick interferon had no inhibitory effect on the formation of T antigen. In adenovirus 12-infected CEC, virus specific structural antigen could not be detected.", "contents": "T antigen synthesis and resistance to interferon in human adenovirus type 12 infected chick cells. Tye specific T antigen formation has been demonstrated in primary and secondary chick embryo cells (CEC) infected with adenovirus type 12. The frequency of cells synthesizing T antigen was closely dependent on the multiplicity of infection (MOI). At a MOI of 2.85 TCD50 per cell, T antigen was formed in 50% of cells. Cycloheximide inhibited T antigen formation while cytosine arabinoside had no such effect. CEC infected with adenovirus 12 produced interferon and T antigen, both appearing early and at about the same time of infection Exogenous chick interferon had no inhibitory effect on the formation of T antigen. In adenovirus 12-infected CEC, virus specific structural antigen could not be detected."}
{"id": "PMID:23663", "title": "Scanning electron microscopy of L-929 cells exposed to interferon and reovirus.", "content": "L-929 cells were studied under the scanning electron microscope (SEM) in the course of reovirus infection with and without prior interferon treatment. Two major stages in the cytopathic effect (CPE) were identified on the basis of fine surface morphology as revealed by SEM. Uninfected control cells were spindle-shaped with microvilli and numerous filopodia and were firmly attached to the substratum. In stage 1 of CPE, the cells lose filopodia and develop large blebs. Stage 2 is characterized by undulating surface and pits on the nearly spherical cells which are devoid of microvilli and filopodia. At all time intervals observed post infection, interferon-treated reovirus-infected cells showed more advanced CPE than the non-interferon-treated reovirus-infected counterpart controls.", "contents": "Scanning electron microscopy of L-929 cells exposed to interferon and reovirus. L-929 cells were studied under the scanning electron microscope (SEM) in the course of reovirus infection with and without prior interferon treatment. Two major stages in the cytopathic effect (CPE) were identified on the basis of fine surface morphology as revealed by SEM. Uninfected control cells were spindle-shaped with microvilli and numerous filopodia and were firmly attached to the substratum. In stage 1 of CPE, the cells lose filopodia and develop large blebs. Stage 2 is characterized by undulating surface and pits on the nearly spherical cells which are devoid of microvilli and filopodia. At all time intervals observed post infection, interferon-treated reovirus-infected cells showed more advanced CPE than the non-interferon-treated reovirus-infected counterpart controls."}
{"id": "PMID:23664", "title": "The effect of supraoptimal temperature on the formation of pseudorabies virus particles.", "content": "Replication of virulent and attenuated strains of pseudorabies virus (PRV) at supraoptimal temperature was inhibited in L cells non-adapted to 40 degrees C. Electron microscopy revealed the prevalence of hollow core particles without nucleoid; both the nuclei and cytoplasm of L cells were markedly altered at supraoptimal temperature. In BHK-21 cells adapted to 40 degrees C only replication of attenuated strains was inhibited whereas the virulent ones reached high titres at this temperature. The particles produced at 40 degrees C by attenuated strains were non-infectious but morphologically normal. The ability of attenuated PRV strains to reproduce in adapted BHK-21 cells at 40 degrees C was in correlation with the degree of their attenuation. Changes in the nuclei and cytoplasm of adapted BHK-21 cells at supraoptimal temperature were not as marked as in L cells.", "contents": "The effect of supraoptimal temperature on the formation of pseudorabies virus particles. Replication of virulent and attenuated strains of pseudorabies virus (PRV) at supraoptimal temperature was inhibited in L cells non-adapted to 40 degrees C. Electron microscopy revealed the prevalence of hollow core particles without nucleoid; both the nuclei and cytoplasm of L cells were markedly altered at supraoptimal temperature. In BHK-21 cells adapted to 40 degrees C only replication of attenuated strains was inhibited whereas the virulent ones reached high titres at this temperature. The particles produced at 40 degrees C by attenuated strains were non-infectious but morphologically normal. The ability of attenuated PRV strains to reproduce in adapted BHK-21 cells at 40 degrees C was in correlation with the degree of their attenuation. Changes in the nuclei and cytoplasm of adapted BHK-21 cells at supraoptimal temperature were not as marked as in L cells."}
{"id": "PMID:23665", "title": "The course of influrenza infection in mice with graft-versus-host reaction.", "content": "The course of influenza infection in mice with a developed graft-versus-host reaction (GVHR) was changed. Due to disturbances in the inflammatory process the pneumonia was delayed and less marked. Consequently, the infected mice died later than controls. Influenza virus reproduction in the lungs was more intensive and its persistence more prolonged. Interferon production in the lungs of mice with GVHR was similar to that in the controls.", "contents": "The course of influrenza infection in mice with graft-versus-host reaction. The course of influenza infection in mice with a developed graft-versus-host reaction (GVHR) was changed. Due to disturbances in the inflammatory process the pneumonia was delayed and less marked. Consequently, the infected mice died later than controls. Influenza virus reproduction in the lungs was more intensive and its persistence more prolonged. Interferon production in the lungs of mice with GVHR was similar to that in the controls."}
{"id": "PMID:23666", "title": "Evaluation of the effectiveness of receptor destroying enzyme preparations.", "content": "A procedure has been developed for testing receptor destroying enzyme (RDE) preparations used to remove nonspecific inhibitors before carrying out haemagglutination inhibition tests with influenza virus. Four criteria should be taken into account: (1) titre of RDE, usually used to indicate the activity of the preparation; (2) neuraminidase activity of the preparation, determined biochemically, which partially corresponds to the RDE titre; (3) direct demonstration of the complete removal of nonspecific inhibitors; and (4) determination that the RDE preparation does not affect specific antibody.", "contents": "Evaluation of the effectiveness of receptor destroying enzyme preparations. A procedure has been developed for testing receptor destroying enzyme (RDE) preparations used to remove nonspecific inhibitors before carrying out haemagglutination inhibition tests with influenza virus. Four criteria should be taken into account: (1) titre of RDE, usually used to indicate the activity of the preparation; (2) neuraminidase activity of the preparation, determined biochemically, which partially corresponds to the RDE titre; (3) direct demonstration of the complete removal of nonspecific inhibitors; and (4) determination that the RDE preparation does not affect specific antibody."}
{"id": "PMID:23667", "title": "Induction of interferon in mice and cell cultures by Mycoplasma pneumoniae.", "content": "Inoculation of mice and L and human embryonic lung (HEL) cell cultures with Mycoplasma pneumoniae failed to induce the production of interferon. M. pneumoniae multiplied in these cell cultures without a marked cytopathic effect. M. pneumoniae induced interferon in human peripheral blood leukocytes with maximum titres of 32 units/ml at 48 hours after infection.", "contents": "Induction of interferon in mice and cell cultures by Mycoplasma pneumoniae. Inoculation of mice and L and human embryonic lung (HEL) cell cultures with Mycoplasma pneumoniae failed to induce the production of interferon. M. pneumoniae multiplied in these cell cultures without a marked cytopathic effect. M. pneumoniae induced interferon in human peripheral blood leukocytes with maximum titres of 32 units/ml at 48 hours after infection."}
{"id": "PMID:23668", "title": "Electron microscopic studies of the replication of mouse cytomegalovirus in mouse embryo cells.", "content": "During the replication a pathogenic and a non-pathogenic strain of mouse cytomegalovirus in mouse embryo cells, three types of progeny virus particles were observed in both cases; the virus yields of the two strains differed considerably.", "contents": "Electron microscopic studies of the replication of mouse cytomegalovirus in mouse embryo cells. During the replication a pathogenic and a non-pathogenic strain of mouse cytomegalovirus in mouse embryo cells, three types of progeny virus particles were observed in both cases; the virus yields of the two strains differed considerably."}
{"id": "PMID:23669", "title": "Autoantibodies in sera of rabbits immunized with influenza virus.", "content": "Rabbits immunized with purified influenza A (H3N2) virus within 4 weeks developed autoantibodies of SMA type (smooth muscle antibodies). In some of them also ABBA (antibodies against brush border of proximal renal tubuli) and ANA (anti-nuclear antibodies) were detected. This autoimmune response was found to be unrelated to either the virus dose or the adjuvant used for immunization. Autoantibodies were not parallel in titre with influenza antibody.", "contents": "Autoantibodies in sera of rabbits immunized with influenza virus. Rabbits immunized with purified influenza A (H3N2) virus within 4 weeks developed autoantibodies of SMA type (smooth muscle antibodies). In some of them also ABBA (antibodies against brush border of proximal renal tubuli) and ANA (anti-nuclear antibodies) were detected. This autoimmune response was found to be unrelated to either the virus dose or the adjuvant used for immunization. Autoantibodies were not parallel in titre with influenza antibody."}
{"id": "PMID:23670", "title": "Ability of human polymorhonuclear blood cells to produce interferon after induction with phage double-stranded RNA.", "content": "The ability of human peripheral blood leukocytes to produce interferon in response to phage double-stranded (ds) RNA was studied. Under the conditions used, interferon was produced not only by lymphocytes but also by polymorphs and monocytes. These \"pure\" cultures showed no marked differences in the degree of interferon production as compared with the mixed leukocyte culture. The involvement of polymorphs in the production of interferon induced by phage ds RNA is discussed.", "contents": "Ability of human polymorhonuclear blood cells to produce interferon after induction with phage double-stranded RNA. The ability of human peripheral blood leukocytes to produce interferon in response to phage double-stranded (ds) RNA was studied. Under the conditions used, interferon was produced not only by lymphocytes but also by polymorphs and monocytes. These \"pure\" cultures showed no marked differences in the degree of interferon production as compared with the mixed leukocyte culture. The involvement of polymorphs in the production of interferon induced by phage ds RNA is discussed."}
{"id": "PMID:23675", "title": "Biochemical studies of pancreatic juice collected by duodenal aspiration and endoscopic cannulation of the main pancreatic duct.", "content": "Biochemical studies of pancreatic juice collected by duodenal aspiration and endoscopic cannulation of the main pancreatic duct were performed and compared in the same fasted normal subjects in seven cases. The comparison of the results shows that under the same stimulation (0.5 CU/kg/hr of GIH secretin and 75 ng/kg/hr of cerulein) the endoscopic cannulation of the main pancreatic duct provides the best values for the maximal secretory capacity. On the other hand, this technique is no better than our current method of duodenal aspiration for the exploration of the enzyme secretion.", "contents": "Biochemical studies of pancreatic juice collected by duodenal aspiration and endoscopic cannulation of the main pancreatic duct. Biochemical studies of pancreatic juice collected by duodenal aspiration and endoscopic cannulation of the main pancreatic duct were performed and compared in the same fasted normal subjects in seven cases. The comparison of the results shows that under the same stimulation (0.5 CU/kg/hr of GIH secretin and 75 ng/kg/hr of cerulein) the endoscopic cannulation of the main pancreatic duct provides the best values for the maximal secretory capacity. On the other hand, this technique is no better than our current method of duodenal aspiration for the exploration of the enzyme secretion."}
{"id": "PMID:23676", "title": "Eastern equine encephalitis in Massachusetts, 1957-1976. A prospective study centered upon analyses of mosquitoes.", "content": "Reappearance of eastern equine encephalitis (EEE) in Massachusetts residents in the 1970's provided an opportunity to assess the predictive value of data on rainfall, EEE in horses, and carriage of EEE virus (EEEV) by mosquitoes, factors which had been studied annually since the last EEE outbreak in 1955-1956. The cycle of multiple cases during 1973-1975 started in a second consecutive year of rainfall that exceeded the annual mean by more than 20 cm, conditions recapitulating the 1955-1956 experience. In 1973, widespread EEE fatalities in horses presaged human cases, another recapitulation of the 1955-1956 experience. However, in 1974, when horses were immunized extensively, no equine cases were seen even though three human fatalities occurred. An unseasonably early appearance of EEEV in mosquitoes was the only basis upon which the threat to humans could have been recognized. These changes in the recognition and distribution of EEEV activity from season to season illustrate the difficulty in making rational decisions regarding widespread aerial insecticide applications for mosquito control.", "contents": "Eastern equine encephalitis in Massachusetts, 1957-1976. A prospective study centered upon analyses of mosquitoes. Reappearance of eastern equine encephalitis (EEE) in Massachusetts residents in the 1970's provided an opportunity to assess the predictive value of data on rainfall, EEE in horses, and carriage of EEE virus (EEEV) by mosquitoes, factors which had been studied annually since the last EEE outbreak in 1955-1956. The cycle of multiple cases during 1973-1975 started in a second consecutive year of rainfall that exceeded the annual mean by more than 20 cm, conditions recapitulating the 1955-1956 experience. In 1973, widespread EEE fatalities in horses presaged human cases, another recapitulation of the 1955-1956 experience. However, in 1974, when horses were immunized extensively, no equine cases were seen even though three human fatalities occurred. An unseasonably early appearance of EEEV in mosquitoes was the only basis upon which the threat to humans could have been recognized. These changes in the recognition and distribution of EEEV activity from season to season illustrate the difficulty in making rational decisions regarding widespread aerial insecticide applications for mosquito control."}
{"id": "PMID:23677", "title": "The oxygen affinity of concentrated human hemoglobin solutions and human blood.", "content": "The log P50 of normal human blood at 37 degrees C, PCO2 = 0, 21, 42, AND 57 MM Hg in the absence and in the presence of 2,3-DPG and ATP, has been determined in the pH range 7.0 to 7.6. Similar data have been obtained for human hemoglobin isotonic solutions at different protein concentrations in the presence of various amounts of each of the cofactors which are known to affect hemoglobin oxygen affinity in blood. It has been found that the addition of KC1, organic phosphates, magnesium ions, and CO2 confers to a 32% human hemoglobin solution the same oxygen affinity (over the entire physiological pH range) of whole blood. Thus there is no room for significant effects caused by some other unidentified molecules or ions.", "contents": "The oxygen affinity of concentrated human hemoglobin solutions and human blood. The log P50 of normal human blood at 37 degrees C, PCO2 = 0, 21, 42, AND 57 MM Hg in the absence and in the presence of 2,3-DPG and ATP, has been determined in the pH range 7.0 to 7.6. Similar data have been obtained for human hemoglobin isotonic solutions at different protein concentrations in the presence of various amounts of each of the cofactors which are known to affect hemoglobin oxygen affinity in blood. It has been found that the addition of KC1, organic phosphates, magnesium ions, and CO2 confers to a 32% human hemoglobin solution the same oxygen affinity (over the entire physiological pH range) of whole blood. Thus there is no room for significant effects caused by some other unidentified molecules or ions."}
{"id": "PMID:23679", "title": "The effect of drugs on fetal heart rate variability.", "content": "Baseline FHR variability has been quantitated into the mathematical indices of differential index (short-term variability) and interval index (long-term variability). Normal values have been determined. The effect that drugs used during labor have on FHR baseline variability has been evaluated. A clinically meaningful change in variability has been observed following low-dose administration of Demerol, morphine, Nisentil, Phenergan, and Vistaril. A statistically significant increase in variability has been observed following administration of magnesium sulfate.", "contents": "The effect of drugs on fetal heart rate variability. Baseline FHR variability has been quantitated into the mathematical indices of differential index (short-term variability) and interval index (long-term variability). Normal values have been determined. The effect that drugs used during labor have on FHR baseline variability has been evaluated. A clinically meaningful change in variability has been observed following low-dose administration of Demerol, morphine, Nisentil, Phenergan, and Vistaril. A statistically significant increase in variability has been observed following administration of magnesium sulfate."}
{"id": "PMID:23680", "title": "Aerobic glycolysis in bone: lactic acid production by rat calvaria cells in culture.", "content": "Considerable data have been accumulated on aerobic glycolysis of intact bone preparations. To test whether aerobic glycolysis is a feature of the bone cells themselves or of the localized conditions within an intact bone, cells isolated from rat calvaria were cultured and the effect of several factors on lactate production was determined. These cells drastically decreased lactate production when the pH in the culture medium was lowered, changing from 100 to 20 percent for a pH shift from 7.4 to 6.75. L-lactate inhibited its own formation by 40 percent at 20 mM. Parathyroid hormone (PTH) (820 U/mg) at a concentration ranging from 0.2 to 5.0 U/ml stimulated slightly the lactate production in a log-linear response, the ratio treated over control changing from 1.1 to 1.3. The maximal stimulation is observed at pH 7.0. Isolated cells respond qualitatively the same as did intact calvaria. Quantitatively, there were significant differences: notably, a smaller response to parathyroid hormone and a higher sensitivity to lowered pH.", "contents": "Aerobic glycolysis in bone: lactic acid production by rat calvaria cells in culture. Considerable data have been accumulated on aerobic glycolysis of intact bone preparations. To test whether aerobic glycolysis is a feature of the bone cells themselves or of the localized conditions within an intact bone, cells isolated from rat calvaria were cultured and the effect of several factors on lactate production was determined. These cells drastically decreased lactate production when the pH in the culture medium was lowered, changing from 100 to 20 percent for a pH shift from 7.4 to 6.75. L-lactate inhibited its own formation by 40 percent at 20 mM. Parathyroid hormone (PTH) (820 U/mg) at a concentration ranging from 0.2 to 5.0 U/ml stimulated slightly the lactate production in a log-linear response, the ratio treated over control changing from 1.1 to 1.3. The maximal stimulation is observed at pH 7.0. Isolated cells respond qualitatively the same as did intact calvaria. Quantitatively, there were significant differences: notably, a smaller response to parathyroid hormone and a higher sensitivity to lowered pH."}
{"id": "PMID:23682", "title": "Time course of the cerebral circulatory response to metabolic depression.", "content": "Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.", "contents": "Time course of the cerebral circulatory response to metabolic depression. Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem."}
{"id": "PMID:23684", "title": "Antipsychotic drugs, neurotransmitters, and schizophrenia.", "content": "Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets for the mental and the extrapyramidal actions, respectively, of these drugs. The fact that dopaminergic hyperfunction induced by amphetamines or dopa may lead to a disturbance mimicking paranoid schizophrenia lends further support for a key role of dopamine in mental functions. Although a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, amino acid, or peptide transmitters in schizophrenia cannot be disregarded.", "contents": "Antipsychotic drugs, neurotransmitters, and schizophrenia. Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets for the mental and the extrapyramidal actions, respectively, of these drugs. The fact that dopaminergic hyperfunction induced by amphetamines or dopa may lead to a disturbance mimicking paranoid schizophrenia lends further support for a key role of dopamine in mental functions. Although a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, amino acid, or peptide transmitters in schizophrenia cannot be disregarded."}
{"id": "PMID:23689", "title": "Quality assessment of a telephone care system utilizing non-physician personnel.", "content": "An approach to providing medical care by telephone is described and its content and quality assessed by means of an outcome study. Pediatric health assistants have been trained to evaluate, triage and offer home management advice in lieu of an office visit for medical problems presented by parents via telephone. During a four-week study period, data were collected on all calls (N = 2520) using a telephone encounter form. Fifty-nine per cent of all calls involved requests for care of illness, 30 per cent of which were independently handled by the health assistant. Quality of care was evaluated for those cases who received advice in home management by means of a seven day follow-up interview with parents (N = 247). Access, parent satisfaction, residual symptoms, and the need for further care were ascertained. Greater than 90 per cent of parents expressed satisfaction and 92 per cent of problems had resolved. Results indicate that this telephone care system can effectively sort out and advise parents in home management for the many minor problems which occur in a pediatric practice, thereby increasing time for direct contact with patients.", "contents": "Quality assessment of a telephone care system utilizing non-physician personnel. An approach to providing medical care by telephone is described and its content and quality assessed by means of an outcome study. Pediatric health assistants have been trained to evaluate, triage and offer home management advice in lieu of an office visit for medical problems presented by parents via telephone. During a four-week study period, data were collected on all calls (N = 2520) using a telephone encounter form. Fifty-nine per cent of all calls involved requests for care of illness, 30 per cent of which were independently handled by the health assistant. Quality of care was evaluated for those cases who received advice in home management by means of a seven day follow-up interview with parents (N = 247). Access, parent satisfaction, residual symptoms, and the need for further care were ascertained. Greater than 90 per cent of parents expressed satisfaction and 92 per cent of problems had resolved. Results indicate that this telephone care system can effectively sort out and advise parents in home management for the many minor problems which occur in a pediatric practice, thereby increasing time for direct contact with patients."}
{"id": "PMID:23690", "title": "Physicians and non-physician health practitioners: the characteristics of their practices and their relationships.", "content": "Six primary care practices which utilize both physician and non-physician practitioner types were studied to measure differences between practitioner types in the care of patients. By chart review 1,369 patient-practitioner encounters were examined. Physicians identified less symptoms and signs in their patients and prescribed less non-drug therapies than did non-physicians. Likewise, at follow-up visits, physicians tended to document less follow-up of these types of problems and therapies than non-physicians. When examining the interaction between practitioners, the highest rates of follow-up of all types of problems and therapies were found when the same practitioner saw the patient at two successive visits to the same clinic. When a physician saw a patient following a previous visit to a nurse practitioner, there was a significant drop-off in the follow-up rate of problems and therapies. However, when a nurse practitioner saw the patient following a previous visit to a physician, the drop-off in follow-up rates was not as striking. These findings indicate that the skills of physician and nonphysician practitioners are potentially complementary. However, this potential is not fully exploited, particularly by physicians.", "contents": "Physicians and non-physician health practitioners: the characteristics of their practices and their relationships. Six primary care practices which utilize both physician and non-physician practitioner types were studied to measure differences between practitioner types in the care of patients. By chart review 1,369 patient-practitioner encounters were examined. Physicians identified less symptoms and signs in their patients and prescribed less non-drug therapies than did non-physicians. Likewise, at follow-up visits, physicians tended to document less follow-up of these types of problems and therapies than non-physicians. When examining the interaction between practitioners, the highest rates of follow-up of all types of problems and therapies were found when the same practitioner saw the patient at two successive visits to the same clinic. When a physician saw a patient following a previous visit to a nurse practitioner, there was a significant drop-off in the follow-up rate of problems and therapies. However, when a nurse practitioner saw the patient following a previous visit to a physician, the drop-off in follow-up rates was not as striking. These findings indicate that the skills of physician and nonphysician practitioners are potentially complementary. However, this potential is not fully exploited, particularly by physicians."}
{"id": "PMID:23691", "title": "Relationship of transmural electrical potential difference to changes in gastric mucosal permeability to H+ and blood flow.", "content": "Chambered in vivo wedges of proximal canine gastric mucosa were used to evaluate the relationship between PD, net H+ and Na+ fluxes, and gastric mucosal nutrient blood flow, as adjudicated by the ability of the mucosa to clear aminopyrine. Assuming that steady state conditions existed during the study, the results indicate that (1) the mean PD/15 minute period is a significant linear function of both net H+ and net Na+ flux and therefore, presumably, of changes in gastric mucosal permeability to cations, and (2) the mean PD/15 minute period is a significant exponential function of gastric mucosal nutrient blood flow, marked reductions in PD occurring at flows of 1 to 1.5 ml or less. If the thesis that acute posttraumatic hemorrhagic gastritis is a consequence of concomitant alterations in gastric mucosal permeability to H+ and reductions in mucosal blood flow is correct, the PD might represent a useful clinical tool for detecting, in susceptible patients, the evolutionary stages of this devastating complication of trauma.", "contents": "Relationship of transmural electrical potential difference to changes in gastric mucosal permeability to H+ and blood flow. Chambered in vivo wedges of proximal canine gastric mucosa were used to evaluate the relationship between PD, net H+ and Na+ fluxes, and gastric mucosal nutrient blood flow, as adjudicated by the ability of the mucosa to clear aminopyrine. Assuming that steady state conditions existed during the study, the results indicate that (1) the mean PD/15 minute period is a significant linear function of both net H+ and net Na+ flux and therefore, presumably, of changes in gastric mucosal permeability to cations, and (2) the mean PD/15 minute period is a significant exponential function of gastric mucosal nutrient blood flow, marked reductions in PD occurring at flows of 1 to 1.5 ml or less. If the thesis that acute posttraumatic hemorrhagic gastritis is a consequence of concomitant alterations in gastric mucosal permeability to H+ and reductions in mucosal blood flow is correct, the PD might represent a useful clinical tool for detecting, in susceptible patients, the evolutionary stages of this devastating complication of trauma."}
{"id": "PMID:23692", "title": "Secretory state of gastric mucosa and its resistance to aspirin injury.", "content": "The influence of the secretory status on gastric mucosal tolerance to aspirin injury was assessed in a canine ex vivo model, which provided two segments of mucosa supplied by a single vascular pedicle in the same dog. Acid secretion was stimulated by intravenous infusion of histamine in one mucosa, whereas the secretory response to histamine was significantly impaired by topical treatment with 16,16-dimethyl prostaglandin E2 in the other. As expected, the secreting mucosa exhibited a twofold greater blood flow than the inhibited mucosa. Exposure of both mucosae to 20 mM aspirin for 30 minutes resulted in the appearance of small multiple superficial erosions. The degree of mucosal injury was not significantly different between the secreting and inhibited mucosae. The extent of mucosal damage was similar to that seen when aspirin in acid was placed on resting mucosa in the same model. These data do not support the hypothesis that histamine-stimulated acid secretion and accompanying increase in gastric mucosal blood flow protects the stomach against aspirin injury.", "contents": "Secretory state of gastric mucosa and its resistance to aspirin injury. The influence of the secretory status on gastric mucosal tolerance to aspirin injury was assessed in a canine ex vivo model, which provided two segments of mucosa supplied by a single vascular pedicle in the same dog. Acid secretion was stimulated by intravenous infusion of histamine in one mucosa, whereas the secretory response to histamine was significantly impaired by topical treatment with 16,16-dimethyl prostaglandin E2 in the other. As expected, the secreting mucosa exhibited a twofold greater blood flow than the inhibited mucosa. Exposure of both mucosae to 20 mM aspirin for 30 minutes resulted in the appearance of small multiple superficial erosions. The degree of mucosal injury was not significantly different between the secreting and inhibited mucosae. The extent of mucosal damage was similar to that seen when aspirin in acid was placed on resting mucosa in the same model. These data do not support the hypothesis that histamine-stimulated acid secretion and accompanying increase in gastric mucosal blood flow protects the stomach against aspirin injury."}
{"id": "PMID:23696", "title": "[Social-gerontological theories of the situation in the lives of the aged--a discussion on geroprophylaxis (author's transl)].", "content": "The contribution discusses the most important theories which chiefly refer in a mainly sociologically orientated way to the explanation of the various forms of the process of aging: activity- and disengagement-theory. Both theories have had an exceptionally strong influence on scientific soziological research since they had become known and the result of this research has made a modification of the theoretical onset necessary. The conclusions to be drawn under socio-economical points of view under, respect of the theory of socialisation, sociology of knowledge and socioeducational points of view will be explained at the end of the contribution.", "contents": "[Social-gerontological theories of the situation in the lives of the aged--a discussion on geroprophylaxis (author's transl)]. The contribution discusses the most important theories which chiefly refer in a mainly sociologically orientated way to the explanation of the various forms of the process of aging: activity- and disengagement-theory. Both theories have had an exceptionally strong influence on scientific soziological research since they had become known and the result of this research has made a modification of the theoretical onset necessary. The conclusions to be drawn under socio-economical points of view under, respect of the theory of socialisation, sociology of knowledge and socioeducational points of view will be explained at the end of the contribution."}
{"id": "PMID:23697", "title": "[The possible use of sociological onsets in theory on the problem of age and surroundings (author's transl)].", "content": "The possibility of using sociological theories on practical problems is a main view point for judging their usefulness. From a scientific-theoretical point of view activity- and disengagement-theory are adequately examined in this contribution. By this it is shown that these theories are lacking mainly in precision and consistency; moreover there is a limitation concerning their relevancy for daily use by the lack of the possibility of producing the variables used in the onsets.", "contents": "[The possible use of sociological onsets in theory on the problem of age and surroundings (author's transl)]. The possibility of using sociological theories on practical problems is a main view point for judging their usefulness. From a scientific-theoretical point of view activity- and disengagement-theory are adequately examined in this contribution. By this it is shown that these theories are lacking mainly in precision and consistency; moreover there is a limitation concerning their relevancy for daily use by the lack of the possibility of producing the variables used in the onsets."}
{"id": "PMID:23698", "title": "[Survey on the gerontological research in the Federal Republic of Germany (author's transl)].", "content": "This survey on the gerontological research shows the topical main accents of work in this field in the Federal Republic of Germany: Social services for aged, old-age-security, social and health situation, and older workers' problems are the most important items of the essay. Empirical examinations are dealt with separately. Moreover, there is a prospect on the different types of projects, research institutions and where they are distributed in the different areas and the different ways of financing this research.", "contents": "[Survey on the gerontological research in the Federal Republic of Germany (author's transl)]. This survey on the gerontological research shows the topical main accents of work in this field in the Federal Republic of Germany: Social services for aged, old-age-security, social and health situation, and older workers' problems are the most important items of the essay. Empirical examinations are dealt with separately. Moreover, there is a prospect on the different types of projects, research institutions and where they are distributed in the different areas and the different ways of financing this research."}
{"id": "PMID:23699", "title": "[Problems of retirement and their mastering (author's transl)].", "content": "Based on four functions (assignment of status and role, making one's living, reasons for social contacts, and structure of time) the importance of work and profession in a society mainly orientated on performance are shown. From this we can conclude that with retirement from the profession a lability of the level of satisfaction can be found. Based on the analysis some measures are discussed which could assist to restabilisation by strengthening the individual competences for overcoming problems connected with loosing professional tasks.", "contents": "[Problems of retirement and their mastering (author's transl)]. Based on four functions (assignment of status and role, making one's living, reasons for social contacts, and structure of time) the importance of work and profession in a society mainly orientated on performance are shown. From this we can conclude that with retirement from the profession a lability of the level of satisfaction can be found. Based on the analysis some measures are discussed which could assist to restabilisation by strengthening the individual competences for overcoming problems connected with loosing professional tasks."}
{"id": "PMID:23700", "title": "[Psycho-social problems in rehabilitation (author's transl)].", "content": "This contribution contains the results of a study on rehabilitation of patients undergoing treatment in the Alpen-Sanatorium in Bad T\u00f6lz, Germany, which was planned as a prestudy for an extensive examination of psycho-social problems of this group of patients and their chances for rehabilitation. The especially important age-group of those between 50- and 60-years-old for a successful geroprophylaxis was chosen. In this essay the connections between graded seriousness of the illness and the social classes of the patients as well as the following problems: difficulties, situated in the personality, general satisfaction with place in life, real worries, disturbances in childhood and youth, and decisive turning points in life, are worked out.", "contents": "[Psycho-social problems in rehabilitation (author's transl)]. This contribution contains the results of a study on rehabilitation of patients undergoing treatment in the Alpen-Sanatorium in Bad T\u00f6lz, Germany, which was planned as a prestudy for an extensive examination of psycho-social problems of this group of patients and their chances for rehabilitation. The especially important age-group of those between 50- and 60-years-old for a successful geroprophylaxis was chosen. In this essay the connections between graded seriousness of the illness and the social classes of the patients as well as the following problems: difficulties, situated in the personality, general satisfaction with place in life, real worries, disturbances in childhood and youth, and decisive turning points in life, are worked out."}
{"id": "PMID:23701", "title": "[Aging and the risk of illness (author's transl)].", "content": "The necessity to conform with the fact of being ill leads to some psycho-social stress which can increase the risk of falling ill in aging persons in numerous ways. Different tendencies in theory (concepts in activity, disengagement and continuity) contain hints on those conditions which guarantee an individually successful taking over the role of old age and this adds to the decrease of the risk of falling ill. Aimed at health-education carried out in time adds to the chance of an adequate behaviour of old people concerning health and illness.", "contents": "[Aging and the risk of illness (author's transl)]. The necessity to conform with the fact of being ill leads to some psycho-social stress which can increase the risk of falling ill in aging persons in numerous ways. Different tendencies in theory (concepts in activity, disengagement and continuity) contain hints on those conditions which guarantee an individually successful taking over the role of old age and this adds to the decrease of the risk of falling ill. Aimed at health-education carried out in time adds to the chance of an adequate behaviour of old people concerning health and illness."}
{"id": "PMID:23702", "title": "[Determinants of the Knowledge of the human aging process (author's transl)].", "content": "1800 man and women were interviewed to get informations on there knowledge of the human aging process. The results showed, that the validity and the amount of these informations correlated with education and socio-economic status.", "contents": "[Determinants of the Knowledge of the human aging process (author's transl)]. 1800 man and women were interviewed to get informations on there knowledge of the human aging process. The results showed, that the validity and the amount of these informations correlated with education and socio-economic status."}
{"id": "PMID:23703", "title": "Hypoxaemia in elderly patients suffering from fractured neck of femur.", "content": "The purpose of this study was to assess the degree and frequency of hypoxaemia in elderly patients with fractured neck of femur and to note the effect of manipulation and internal fixation on these measurements. Twenty-seven patients aged between 44 and 93 were studied for 5 days after the fracture and for 5 days after surgery. The fractures were treated by internal fixation under either general anaesthesia or spinal analgesia. The arterial oxygen tension following the fracture but before surgery was low relative to the ages of the patients, and the arterial carbon dioxide tension was low in twenty-five out of twenty-seven patients. There was also a significant increase in the dead space/tidal volume ratio (VD/VT) and the alveolar-arterial oxygen tension difference, (A--a)DO2 in eight out of nine patients in the first 5 days following the fracture. The mean arterial oxygen tension was still reduced up to 5 days postoperatively. The VD/VT ratio returned to normal postoperatively although the (A-a)DO2 remained elevated. The haemoglobin and platelet levels following the fracture and before surgery were low, although not remarkably so, and there was no significant change post-operatively. There were no significant changes in the electrocardiograph or the chest radiographs. These results and their implications are discussed.", "contents": "Hypoxaemia in elderly patients suffering from fractured neck of femur. The purpose of this study was to assess the degree and frequency of hypoxaemia in elderly patients with fractured neck of femur and to note the effect of manipulation and internal fixation on these measurements. Twenty-seven patients aged between 44 and 93 were studied for 5 days after the fracture and for 5 days after surgery. The fractures were treated by internal fixation under either general anaesthesia or spinal analgesia. The arterial oxygen tension following the fracture but before surgery was low relative to the ages of the patients, and the arterial carbon dioxide tension was low in twenty-five out of twenty-seven patients. There was also a significant increase in the dead space/tidal volume ratio (VD/VT) and the alveolar-arterial oxygen tension difference, (A--a)DO2 in eight out of nine patients in the first 5 days following the fracture. The mean arterial oxygen tension was still reduced up to 5 days postoperatively. The VD/VT ratio returned to normal postoperatively although the (A-a)DO2 remained elevated. The haemoglobin and platelet levels following the fracture and before surgery were low, although not remarkably so, and there was no significant change post-operatively. There were no significant changes in the electrocardiograph or the chest radiographs. These results and their implications are discussed."}
{"id": "PMID:23704", "title": "The effect of diazepam and lorazepam on awareness during anaesthesia for Caesarian section.", "content": "One hundred-and-eighty-three patients having general anaesthesia for Caesarian section were given lorazepam or diazepam intravenously immediately following delivery. The incidence of unpleasant recall was comparable with the reports of other workers. There was no evidence of a specific retrograde amnesic effect by either drug. Neither agent appeared to affect cardiovascular stability, uterine contraction, the reversal of muscle relaxant or the time to recovery of protective reflexes. The patients tended to be drowsier after lorazepam but as safe as after diazepam so far as circulation, respiration and protective reflexes were concerned.", "contents": "The effect of diazepam and lorazepam on awareness during anaesthesia for Caesarian section. One hundred-and-eighty-three patients having general anaesthesia for Caesarian section were given lorazepam or diazepam intravenously immediately following delivery. The incidence of unpleasant recall was comparable with the reports of other workers. There was no evidence of a specific retrograde amnesic effect by either drug. Neither agent appeared to affect cardiovascular stability, uterine contraction, the reversal of muscle relaxant or the time to recovery of protective reflexes. The patients tended to be drowsier after lorazepam but as safe as after diazepam so far as circulation, respiration and protective reflexes were concerned."}
{"id": "PMID:23705", "title": "APUD cells and the apudomas. A concept relevant to anaesthesia and endocrinology.", "content": "A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described.", "contents": "APUD cells and the apudomas. A concept relevant to anaesthesia and endocrinology. A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described."}
{"id": "PMID:23706", "title": "[Anaphylactoid reactions following administration of plasma substitutes in man. Prevention of this side-effect of haemaccel by premedication with H1- and H2-receptor antagonists (author's transl)].", "content": "In a randomized controlled single blind trial in 50 volunteers the problem was investigated whether a combination of dimethpyrindene (0.1 mg/kg b.w.) and cimetidine (10 mg/kg b.w.) could prevent anaphylactoid or allergoid reactions following Haemaccel infusion. In the control group 6 anaphylactoid and 9 allergoid reactions were observed, in the H1 + H2-group, however, none of those reactions occured. No single wheal could be detected. It is considered appropriate to recommend the general use premedication of an H1 + H2-blocker before all anaesthetics and operations. This mainly depends on further clinical trials with the antihistaminic drugs concerning their side-effects under various conditions.", "contents": "[Anaphylactoid reactions following administration of plasma substitutes in man. Prevention of this side-effect of haemaccel by premedication with H1- and H2-receptor antagonists (author's transl)]. In a randomized controlled single blind trial in 50 volunteers the problem was investigated whether a combination of dimethpyrindene (0.1 mg/kg b.w.) and cimetidine (10 mg/kg b.w.) could prevent anaphylactoid or allergoid reactions following Haemaccel infusion. In the control group 6 anaphylactoid and 9 allergoid reactions were observed, in the H1 + H2-group, however, none of those reactions occured. No single wheal could be detected. It is considered appropriate to recommend the general use premedication of an H1 + H2-blocker before all anaesthetics and operations. This mainly depends on further clinical trials with the antihistaminic drugs concerning their side-effects under various conditions."}
{"id": "PMID:23707", "title": "[Morphokinetic reactions in the thyroid, parathyroid, and tracheal glands of the albino rat after anaesthesia with thiobutabarbitone sodium and diethyl ether (author's transl)].", "content": "A significant decrease was observed in nuclear volume of the follicular cells of the thyroid gland and the cells of the parathyroid of albino rats subjected to ether anaesthesia, in contrast to generally unchanged nuclear size in animals anaesthetized by thiobutabarbitone sodium. It is suggested that ether exerts its depressant influence mainly by direct action on the function of the follicular cells of the thyroid. Thiobutabarbitone Sodium probably influences thyroid function especially by its antithyroid-drug effects, which have been reported by other authors. The highly significant increase of nuclear volume in the tracheal glands during ether narcosis is referred to the mucous secretion activating stimulus of ether vapors.", "contents": "[Morphokinetic reactions in the thyroid, parathyroid, and tracheal glands of the albino rat after anaesthesia with thiobutabarbitone sodium and diethyl ether (author's transl)]. A significant decrease was observed in nuclear volume of the follicular cells of the thyroid gland and the cells of the parathyroid of albino rats subjected to ether anaesthesia, in contrast to generally unchanged nuclear size in animals anaesthetized by thiobutabarbitone sodium. It is suggested that ether exerts its depressant influence mainly by direct action on the function of the follicular cells of the thyroid. Thiobutabarbitone Sodium probably influences thyroid function especially by its antithyroid-drug effects, which have been reported by other authors. The highly significant increase of nuclear volume in the tracheal glands during ether narcosis is referred to the mucous secretion activating stimulus of ether vapors."}
{"id": "PMID:23713", "title": "Chest pain: coronary or esophageal?", "content": "Although it is often relatively easy for the clinician to differentiate between the heart and the esophagus as sources of chest pain, there remains a substantial minority of patients in whom this task is difficult. We have attempted to review points of differential significance which can be elicited through assessment of the patient's symptoms. Diagnostic studies for the detection of esophageal disorders have been reviewed, and the relative usefulness of these studies has been emphasized. As the result of advancements in diagnostic techniques as well as better understanding of esophageal pathophysiology, the clinician is now capable of accurately identifying the esophagus as the source of chest pain.", "contents": "Chest pain: coronary or esophageal? Although it is often relatively easy for the clinician to differentiate between the heart and the esophagus as sources of chest pain, there remains a substantial minority of patients in whom this task is difficult. We have attempted to review points of differential significance which can be elicited through assessment of the patient's symptoms. Diagnostic studies for the detection of esophageal disorders have been reviewed, and the relative usefulness of these studies has been emphasized. As the result of advancements in diagnostic techniques as well as better understanding of esophageal pathophysiology, the clinician is now capable of accurately identifying the esophagus as the source of chest pain."}
{"id": "PMID:23718", "title": "[Optimal conditions of alpha-amylase production by Aspergillus oryzae in liquid media].", "content": "The alpha-amylase secretion in a mineral culture medium containing starch and glucose follow the lysis of mycelium. This lysis seems to result from the hydrolysing action of dextranase and levulanase on cell wall. Cell lysis and amylase secretion are greatly enhanced by pH elevation of culture medium (optimal pH 8,8). In such conditions of production the amylase is not stable but can be stabilized by addition of starch. A method is described using pH and starch content modifications, which allows to obtain an amylase production three times greater than in standard culture medium.", "contents": "[Optimal conditions of alpha-amylase production by Aspergillus oryzae in liquid media]. The alpha-amylase secretion in a mineral culture medium containing starch and glucose follow the lysis of mycelium. This lysis seems to result from the hydrolysing action of dextranase and levulanase on cell wall. Cell lysis and amylase secretion are greatly enhanced by pH elevation of culture medium (optimal pH 8,8). In such conditions of production the amylase is not stable but can be stabilized by addition of starch. A method is described using pH and starch content modifications, which allows to obtain an amylase production three times greater than in standard culture medium."}
{"id": "PMID:23720", "title": "[Study of E. coli penicillin amidase. The pH-dependence of the enzymatic inactivation kinetics].", "content": "The pH-dependence of the inactivation rate constant of penicillin amidase at a temperature of 40 degrees C was studied. It was shown that in all cases the enzyme inactivation corresponded to the kinetics of the reaction of the 1st order. The pH-dependence profile was found to be bell-shaped, the effect of transfer from the highest to the lowest values of the inactivation rate constants increasing more than 100 times. On the basis of the data obtained and published earlier it was concluded that the enzyme inactivation proceeded in accordance with the scheme in which out of 3 equilibrium ionic forms of penicillin amidase, i.e. \"acid\", \"neutral\" and \"alkaline\" the neutral form of the active enzyme was most stable. Kinetic analysis of the scheme was carried out and it was shown that the dependence found was in accordance with the theoretical curve in which the pK values of the ionogenic groups controlling the interconvertions between the penicillin amidase forms were equal to 2.4 and 10.1 at a temperature of 40 degrees C. The value of the inactivation rate constant of the \"acid\" or \"alkaline\" form was equal to 5.95 min-1, while the \"neutral\" form of the enzyme was characterized by the inactivation rate constant equal to 5.1.10(-4) min-1. A mechanism for the enzyme inactivation was proposed. According to this mechanism, destruction of the salt bridge in the native structure of penicillin amidase resulted in production of extremely labile forms of the enzyme as compared to the native form.", "contents": "[Study of E. coli penicillin amidase. The pH-dependence of the enzymatic inactivation kinetics]. The pH-dependence of the inactivation rate constant of penicillin amidase at a temperature of 40 degrees C was studied. It was shown that in all cases the enzyme inactivation corresponded to the kinetics of the reaction of the 1st order. The pH-dependence profile was found to be bell-shaped, the effect of transfer from the highest to the lowest values of the inactivation rate constants increasing more than 100 times. On the basis of the data obtained and published earlier it was concluded that the enzyme inactivation proceeded in accordance with the scheme in which out of 3 equilibrium ionic forms of penicillin amidase, i.e. \"acid\", \"neutral\" and \"alkaline\" the neutral form of the active enzyme was most stable. Kinetic analysis of the scheme was carried out and it was shown that the dependence found was in accordance with the theoretical curve in which the pK values of the ionogenic groups controlling the interconvertions between the penicillin amidase forms were equal to 2.4 and 10.1 at a temperature of 40 degrees C. The value of the inactivation rate constant of the \"acid\" or \"alkaline\" form was equal to 5.95 min-1, while the \"neutral\" form of the enzyme was characterized by the inactivation rate constant equal to 5.1.10(-4) min-1. A mechanism for the enzyme inactivation was proposed. According to this mechanism, destruction of the salt bridge in the native structure of penicillin amidase resulted in production of extremely labile forms of the enzyme as compared to the native form."}
{"id": "PMID:23719", "title": "Intercellular junctions in the organ of Corti.", "content": "The intercellular junctions between adjacent supporting cells and between apposed hair and supporting cells in the organ of Corti of cat and human were studied. At the endolymphatic surface, the intercellular space was closed by a series of tight junctions (zonula occludens), whereas there were no tight junctions at the basilar membrane surface of the neuroepithelium. Beneath the adlumenal zonula occludens between adjacent supporting cells, a zonula adherens (intermediate junction, \"desmosone\") was found. Many gap junctions joined apposed supporting cells both within apposed hair and supporting cells, membrane specialization sharing the morphological characterics of both the macula adherens and zonula adherens was found. Between cells, there were short areas of parallel limiting membranes separated by a 20A intercellular space. These areas were suggestive but not characteristic of gap junctional specialization. The functional significance of the junctional specialization between cells in the organ of Corti is discussed.", "contents": "Intercellular junctions in the organ of Corti. The intercellular junctions between adjacent supporting cells and between apposed hair and supporting cells in the organ of Corti of cat and human were studied. At the endolymphatic surface, the intercellular space was closed by a series of tight junctions (zonula occludens), whereas there were no tight junctions at the basilar membrane surface of the neuroepithelium. Beneath the adlumenal zonula occludens between adjacent supporting cells, a zonula adherens (intermediate junction, \"desmosone\") was found. Many gap junctions joined apposed supporting cells both within apposed hair and supporting cells, membrane specialization sharing the morphological characterics of both the macula adherens and zonula adherens was found. Between cells, there were short areas of parallel limiting membranes separated by a 20A intercellular space. These areas were suggestive but not characteristic of gap junctional specialization. The functional significance of the junctional specialization between cells in the organ of Corti is discussed."}
{"id": "PMID:23732", "title": "A pleiotropic mutant of Rhodopseudomonas capsulata defective in nitrogen metabolism.", "content": "Wild type strains of Rhodopseudomonas capsulata typically can use N2, NH+4, or various nitrogenous organic compounds as N sources for photosynthetic growth. One class of mutants selected for inability to grow on N2 (Nif-) also shows simultaneous loss of capacity to obtain N from numerous organic substrates. When supplied at relatively high concentrations, ammonia can be used as the sole N source for growth of such strains. Enzymatic analysis of one mutant (W11) indicates that the pleiotropic effect on N nutrition is neither due to detectable alteration in the activities of nitrogenase or the initial enzymes responsible for bulk assimilation of ammonia (glutamine synthetase and glutamate synthase) nor to absence of systems required for catabolism of organic N sources. The phenotype of W11 (Nit-; defective in N metabolism) appears to result from loss of ability to grow using low concentrations of ammonia (supplied externally or generated in vivo).", "contents": "A pleiotropic mutant of Rhodopseudomonas capsulata defective in nitrogen metabolism. Wild type strains of Rhodopseudomonas capsulata typically can use N2, NH+4, or various nitrogenous organic compounds as N sources for photosynthetic growth. One class of mutants selected for inability to grow on N2 (Nif-) also shows simultaneous loss of capacity to obtain N from numerous organic substrates. When supplied at relatively high concentrations, ammonia can be used as the sole N source for growth of such strains. Enzymatic analysis of one mutant (W11) indicates that the pleiotropic effect on N nutrition is neither due to detectable alteration in the activities of nitrogenase or the initial enzymes responsible for bulk assimilation of ammonia (glutamine synthetase and glutamate synthase) nor to absence of systems required for catabolism of organic N sources. The phenotype of W11 (Nit-; defective in N metabolism) appears to result from loss of ability to grow using low concentrations of ammonia (supplied externally or generated in vivo)."}
{"id": "PMID:23733", "title": "Some properties of formate dehydrogenase, accumulation and incorporation of 185W-tungsten into proteins of Clostridium formicoaceticum.", "content": "Formate dehydrogenase of Clostridium formicoaceticum used only methyl and benzyl viologen, but not NAD as electron acceptor. The S0.5 values were 0.9 X 10(-4) M for formate and 5.8 X 10(-3) M for methyl viologen. Using potassium phosphate buffer a pH-optimum of 7.9 was observed. The initial velocity of the formate dehydrogenase activity reached a maximum at 70 degrees C, whereas the activity was stable only up to 50 degrees C. The level of formate dehydrogenase in C. formicoaceticum was increased to its maximum when 10(-6) M selenite and 10(-7) M tungstate were added to a synthetic medium. Addition of molybdate instead of tungstate did not increase the level of formate dehydrogenase. 185W-tungsten was concentrated about 100-fold by C. formicoaceticum; molybdate had no major effect on the uptake of tungsten. 185W-tungsten was found almost exclusively in the soluble fluid and was predominantly recovered after chromatography in a protein of about 88000 molecular weight. Occasionally a labelled protein of low molecular weight was observed. Again molybdate added even in high molar excess did not influence the labelling pattern. No radioactivity peak could be obtained at the elution peak of formate dehydrogenase activity. The extreme instability of formate dehydrogenase prevented further purification.", "contents": "Some properties of formate dehydrogenase, accumulation and incorporation of 185W-tungsten into proteins of Clostridium formicoaceticum. Formate dehydrogenase of Clostridium formicoaceticum used only methyl and benzyl viologen, but not NAD as electron acceptor. The S0.5 values were 0.9 X 10(-4) M for formate and 5.8 X 10(-3) M for methyl viologen. Using potassium phosphate buffer a pH-optimum of 7.9 was observed. The initial velocity of the formate dehydrogenase activity reached a maximum at 70 degrees C, whereas the activity was stable only up to 50 degrees C. The level of formate dehydrogenase in C. formicoaceticum was increased to its maximum when 10(-6) M selenite and 10(-7) M tungstate were added to a synthetic medium. Addition of molybdate instead of tungstate did not increase the level of formate dehydrogenase. 185W-tungsten was concentrated about 100-fold by C. formicoaceticum; molybdate had no major effect on the uptake of tungsten. 185W-tungsten was found almost exclusively in the soluble fluid and was predominantly recovered after chromatography in a protein of about 88000 molecular weight. Occasionally a labelled protein of low molecular weight was observed. Again molybdate added even in high molar excess did not influence the labelling pattern. No radioactivity peak could be obtained at the elution peak of formate dehydrogenase activity. The extreme instability of formate dehydrogenase prevented further purification."}
{"id": "PMID:23734", "title": "[Metabolic products of microorganisms. 166. Optimization of the desferri-ferricrocin production by Aspergillus viridi-nutans Ducker & Thrower (author's transl)].", "content": "At low iron(III)-concentrations (less than 10(-5) M) the fungus Aspergillus viridi-nutans Ducker & Thrower excretes desferri-ferricrocin as the main sideramine into the culture medium. While this compound accounts for 95% of the sideramines produced, small amounts of additional sideramines may also be detected. In a search for an inexpensive nutrient medium for optimum production of desferri-ferricrocin, experiments using shake flasks with good aeration were undertaken initially. The best medium conditions were then employed in a fermentor system. In a 20-1 fermentor with \"intensor\" system, it was shown that at certain growth rates there was an inverse correlation between rate of growth and rate of sideramine production. A defined nutrient medium of glucose plus acetate as carbon sources, and urea or ammonium acetate as nitrogen sources was used. Two different feeding regimens were used in response to changes of pH or to changes of partial pressure of oxygen in the submerged culture: acetic acid/urea or acetic acid/ammonium acetate additions regulated these conditions. The rate of sideramine production under such feeding achieved a maximum of 20 mg 1(-1) h-1 over a period of several days.", "contents": "[Metabolic products of microorganisms. 166. Optimization of the desferri-ferricrocin production by Aspergillus viridi-nutans Ducker & Thrower (author's transl)]. At low iron(III)-concentrations (less than 10(-5) M) the fungus Aspergillus viridi-nutans Ducker & Thrower excretes desferri-ferricrocin as the main sideramine into the culture medium. While this compound accounts for 95% of the sideramines produced, small amounts of additional sideramines may also be detected. In a search for an inexpensive nutrient medium for optimum production of desferri-ferricrocin, experiments using shake flasks with good aeration were undertaken initially. The best medium conditions were then employed in a fermentor system. In a 20-1 fermentor with \"intensor\" system, it was shown that at certain growth rates there was an inverse correlation between rate of growth and rate of sideramine production. A defined nutrient medium of glucose plus acetate as carbon sources, and urea or ammonium acetate as nitrogen sources was used. Two different feeding regimens were used in response to changes of pH or to changes of partial pressure of oxygen in the submerged culture: acetic acid/urea or acetic acid/ammonium acetate additions regulated these conditions. The rate of sideramine production under such feeding achieved a maximum of 20 mg 1(-1) h-1 over a period of several days."}
{"id": "PMID:23735", "title": "Control of the chemotactic behavior of Bacillus subtilis cells.", "content": "The effects of nigericin, valinomycin and some lipophilic cations on the motile behavior of non-starved and methionine-straved Bacillus subtilis cells were studied. For valinomycin and nigericin a quantitative relationship between the flux in the proton-motive force and the duration of the twiddle response was found. Lipophilic cations bind to the ion gate controlling the twiddle frequency and thereby cause the cells to swim smoothly. To explain the transmission of the chemotactic signal a model is given in which receptors, a hyperpolarizing wave, an ion gate and two methylation sites, viz. methyl-accepting chemotaxis proteins and a further methylation site (MT), play a role. For the transmission of the signal caused by an attractant both the hyperpolarizing wave and an interaction between receptor and methylation site (MT) are needed. The methyl-accepting chemotaxis proteins are involved in the adaptation/deadaptation to altered levels of attractant. Artificial changes in the proton-motive force act directly on the ion gate, which finally controlls the twiddle frequency of the cells.", "contents": "Control of the chemotactic behavior of Bacillus subtilis cells. The effects of nigericin, valinomycin and some lipophilic cations on the motile behavior of non-starved and methionine-straved Bacillus subtilis cells were studied. For valinomycin and nigericin a quantitative relationship between the flux in the proton-motive force and the duration of the twiddle response was found. Lipophilic cations bind to the ion gate controlling the twiddle frequency and thereby cause the cells to swim smoothly. To explain the transmission of the chemotactic signal a model is given in which receptors, a hyperpolarizing wave, an ion gate and two methylation sites, viz. methyl-accepting chemotaxis proteins and a further methylation site (MT), play a role. For the transmission of the signal caused by an attractant both the hyperpolarizing wave and an interaction between receptor and methylation site (MT) are needed. The methyl-accepting chemotaxis proteins are involved in the adaptation/deadaptation to altered levels of attractant. Artificial changes in the proton-motive force act directly on the ion gate, which finally controlls the twiddle frequency of the cells."}
{"id": "PMID:23736", "title": "Purification and properties of beta-ketothiolase from Zoogloea ramigera.", "content": "beta-Ketothiolase from Zoogloea ramigera I-16-M was purified 140-fold to electrophoretic homogeneity. The bacterium appeared to contain a single isoenzyme of beta-ketothiolase with a molecular weight of 190 000, as determined by Sephadex G-200 gel filtration. The monomer molecular weight was 44 000, as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The native enzyme thus appeared to be a tetramer with identical subunits. The enzyme showed a pH optimum of 7.5 in the condensation reaction, and 8.5 in the thiolysis reaction. The enzyme employed a Bi Bi ping pong mechanism for the forward thiolysis reaction. The apparent Km value for acetoacetyl coenzyme A in the thiolysis reaction was 10 micron, and that for coenzyme A was 8.5 micron. The apparent Km value for acetyl coenzyme A in the condensation reaction was 0.33 mM. The condensation reaction was inhibited by coenzyme A concentrations lower than 0.1 mM. The enzyme was stable in the presence of dithiothreitol and other SH-compounds, but was strongly inhibited by 0.4 mM p-chloromercuribenzoate.", "contents": "Purification and properties of beta-ketothiolase from Zoogloea ramigera. beta-Ketothiolase from Zoogloea ramigera I-16-M was purified 140-fold to electrophoretic homogeneity. The bacterium appeared to contain a single isoenzyme of beta-ketothiolase with a molecular weight of 190 000, as determined by Sephadex G-200 gel filtration. The monomer molecular weight was 44 000, as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The native enzyme thus appeared to be a tetramer with identical subunits. The enzyme showed a pH optimum of 7.5 in the condensation reaction, and 8.5 in the thiolysis reaction. The enzyme employed a Bi Bi ping pong mechanism for the forward thiolysis reaction. The apparent Km value for acetoacetyl coenzyme A in the thiolysis reaction was 10 micron, and that for coenzyme A was 8.5 micron. The apparent Km value for acetyl coenzyme A in the condensation reaction was 0.33 mM. The condensation reaction was inhibited by coenzyme A concentrations lower than 0.1 mM. The enzyme was stable in the presence of dithiothreitol and other SH-compounds, but was strongly inhibited by 0.4 mM p-chloromercuribenzoate."}
{"id": "PMID:23737", "title": "Glucose-6-phosphate dehydrogenase of Anabaena sp. Kinetic and molecular properties.", "content": "The kinetic and molecular properties of cyanobacterial glucose-6-phosphate dehydrogenase, partly purified from Anabaena sp. ATCC 27893, show that it undergoes relatively slow, reversible transitions between different aggregation states which differ in catalytic activity. Sucrose gradient centrifugation and polyacrylamide gel electrophoresis reveal three pincipal forms, with approximate molecular weights of 120 000 (M1), 240 000 (M2) and 345 000 (M3). The relative catalytic activities are: M1 less than M2 less than M3. In concentrated solutions of the enzyme, the equilibrium favors the more active, oligomeric forms. Dilution in the absence of effectors shifts the equilibrium in favor of the M1 form, with a marked diminution of catalytic activity. This transition is prevented by a substrate, glucose-6-phosphate, and also by glutamine. The other substrate, nicotinamide adenine dinucleotide phosphate (NADP+), and (in crude cell-free extracts) ribulose-1,5-diphosphate are negative effectors, which tend to maintain the enzyme in the M1 form. The equilibrium state between different forms of the enzyme is also strongly dependent on hydrogen ion concentration. Although the optimal pH for catalytic activity is 7.4, dissociation to the hypoactive M1 form is favored at pH values above 7; a pH of 6.5 is optimal for maintenance of the enzyme in the active state. Reduced nicotamide adenine dinucleotide phosphate (NADPH) and adenosine 5'-triphosphate (ATP), inhibit catalytic activity, but do not significantly affect the equilibrium state. The relevance of these findings to the regulation of enzyme activity in vivo is discussed.", "contents": "Glucose-6-phosphate dehydrogenase of Anabaena sp. Kinetic and molecular properties. The kinetic and molecular properties of cyanobacterial glucose-6-phosphate dehydrogenase, partly purified from Anabaena sp. ATCC 27893, show that it undergoes relatively slow, reversible transitions between different aggregation states which differ in catalytic activity. Sucrose gradient centrifugation and polyacrylamide gel electrophoresis reveal three pincipal forms, with approximate molecular weights of 120 000 (M1), 240 000 (M2) and 345 000 (M3). The relative catalytic activities are: M1 less than M2 less than M3. In concentrated solutions of the enzyme, the equilibrium favors the more active, oligomeric forms. Dilution in the absence of effectors shifts the equilibrium in favor of the M1 form, with a marked diminution of catalytic activity. This transition is prevented by a substrate, glucose-6-phosphate, and also by glutamine. The other substrate, nicotinamide adenine dinucleotide phosphate (NADP+), and (in crude cell-free extracts) ribulose-1,5-diphosphate are negative effectors, which tend to maintain the enzyme in the M1 form. The equilibrium state between different forms of the enzyme is also strongly dependent on hydrogen ion concentration. Although the optimal pH for catalytic activity is 7.4, dissociation to the hypoactive M1 form is favored at pH values above 7; a pH of 6.5 is optimal for maintenance of the enzyme in the active state. Reduced nicotamide adenine dinucleotide phosphate (NADPH) and adenosine 5'-triphosphate (ATP), inhibit catalytic activity, but do not significantly affect the equilibrium state. The relevance of these findings to the regulation of enzyme activity in vivo is discussed."}
{"id": "PMID:23738", "title": "The role of vanadium in green plants. III. Influence on cell division of Chlorella.", "content": "Vanadium, although essential for growth and chlorophyll formation in unicellular green algae, reveals toxic influences on cell division of Chlorella pyrenoidosa, these disturbances arising in the same range of V-concentrations as the known positive effects of the trace metal. In permanent light, as documented by cell volume statistics, vanadium (4-10(-7) g-at/1 as NH4VO3) causes a significant shift of the distribution maxima to higher values of the algal cell volume, the shift having its optimum at 10(-5) g-at V/1. It is documented in pH-constant liquid culture that this effect is not due to a change of pH in the nutrient medium. Under synchronous conditions of algal cultivation (16:8h), vanadium causes a total arrest of cell division after 3 periods; this stop lasts for the next 3 cycles. Afterwards, asynchronous divisions newly occur and lead to generally larger autospores. Staining of algal cell nuclei revealed an inhibitory V-effect on nuclear division, yielding giant nuclei with multiple sets of chromosomes, and thereby limiting cell division. Under these conditions, Chlorella pyrenoidosa is not synchronizable in presence of vanadium.", "contents": "The role of vanadium in green plants. III. Influence on cell division of Chlorella. Vanadium, although essential for growth and chlorophyll formation in unicellular green algae, reveals toxic influences on cell division of Chlorella pyrenoidosa, these disturbances arising in the same range of V-concentrations as the known positive effects of the trace metal. In permanent light, as documented by cell volume statistics, vanadium (4-10(-7) g-at/1 as NH4VO3) causes a significant shift of the distribution maxima to higher values of the algal cell volume, the shift having its optimum at 10(-5) g-at V/1. It is documented in pH-constant liquid culture that this effect is not due to a change of pH in the nutrient medium. Under synchronous conditions of algal cultivation (16:8h), vanadium causes a total arrest of cell division after 3 periods; this stop lasts for the next 3 cycles. Afterwards, asynchronous divisions newly occur and lead to generally larger autospores. Staining of algal cell nuclei revealed an inhibitory V-effect on nuclear division, yielding giant nuclei with multiple sets of chromosomes, and thereby limiting cell division. Under these conditions, Chlorella pyrenoidosa is not synchronizable in presence of vanadium."}
{"id": "PMID:23742", "title": "[Investigations of carbromal metabolism (author's transl)].", "content": "Erythro-2-Brom-2-ethyl-3-hydroxybutyramide has been isolated from the urines of patients with Carbromal intoxications as well as from the urine of rat, mouse and dog treated with either Carbromal or with 2-Brom-2-ethyl-acetamide. The identification of the excreted and synthetized metabolite was carried out by means of IR, Mass and NMR spectroscopy. Along with the erythro-2-Brom-2-ethyl-3-hydroxybutyramide one other bromine containing compound was isolated after Carbromal application only, its mass spectrum and rel. RF values having the same characteristics as the synthetized erythro-2-Brom-2-ethyl-3-hydroxybutyrylcarbamide. However, the purification of this metabolite so far has not been successful.", "contents": "[Investigations of carbromal metabolism (author's transl)]. Erythro-2-Brom-2-ethyl-3-hydroxybutyramide has been isolated from the urines of patients with Carbromal intoxications as well as from the urine of rat, mouse and dog treated with either Carbromal or with 2-Brom-2-ethyl-acetamide. The identification of the excreted and synthetized metabolite was carried out by means of IR, Mass and NMR spectroscopy. Along with the erythro-2-Brom-2-ethyl-3-hydroxybutyramide one other bromine containing compound was isolated after Carbromal application only, its mass spectrum and rel. RF values having the same characteristics as the synthetized erythro-2-Brom-2-ethyl-3-hydroxybutyrylcarbamide. However, the purification of this metabolite so far has not been successful."}
{"id": "PMID:23748", "title": "Partial purification of somatomedin from human plasma.", "content": "Fractional precipitation of human plasma using ethanol, followed by chromatography on S.P. Sephadex, yielded a somatomedin-enriched fraction freed from substantial amounts of inhibitory substances. Heat coagulation of the proteins present in this fraction allowed the recovery of appreciable amounts of active components which were then chromatographed on Sephadex G-75 and S.P. Sephadex. A major part of the activity was associated with components less than 4,000 daltons, suggesting that somatomedin, or an active fragment thereof, had been dissociated from a carrier protein by the heat treatment. The range of pH employed throughout was 5.3-9.8. Recoveries of about 30% of biological activity with fold-purification up to 38, as measured by radioactive sulphate uptake in the chick pelvic cartilage assay, were higher than those obtained using acid-ethanol extraction.", "contents": "Partial purification of somatomedin from human plasma. Fractional precipitation of human plasma using ethanol, followed by chromatography on S.P. Sephadex, yielded a somatomedin-enriched fraction freed from substantial amounts of inhibitory substances. Heat coagulation of the proteins present in this fraction allowed the recovery of appreciable amounts of active components which were then chromatographed on Sephadex G-75 and S.P. Sephadex. A major part of the activity was associated with components less than 4,000 daltons, suggesting that somatomedin, or an active fragment thereof, had been dissociated from a carrier protein by the heat treatment. The range of pH employed throughout was 5.3-9.8. Recoveries of about 30% of biological activity with fold-purification up to 38, as measured by radioactive sulphate uptake in the chick pelvic cartilage assay, were higher than those obtained using acid-ethanol extraction."}
{"id": "PMID:23749", "title": "Isolation of Sindbis (alphavirus) and Leanyer viruses from mosquitoes collected in the Northern Territory of Australia, 1974.", "content": "Mosquitoes collected near Darwin, Northern Territory, in 1974 yielded two virus strains. One was identified as Sindbis virus, not previously isolated from the Northern Territory. The other is antigenically distinct from viruses previously isolated from arthropods in Australia, and the name \"Leanyer\" is proposed for it. Its properties suggest that it may be a togavirus serologically unrelated to available alphaviruses and flaviviruses.", "contents": "Isolation of Sindbis (alphavirus) and Leanyer viruses from mosquitoes collected in the Northern Territory of Australia, 1974. Mosquitoes collected near Darwin, Northern Territory, in 1974 yielded two virus strains. One was identified as Sindbis virus, not previously isolated from the Northern Territory. The other is antigenically distinct from viruses previously isolated from arthropods in Australia, and the name \"Leanyer\" is proposed for it. Its properties suggest that it may be a togavirus serologically unrelated to available alphaviruses and flaviviruses."}
{"id": "PMID:23750", "title": "Effects of 6 hours hypoxic and cold exposure on urinary electrolyte and catecholamine excretion.", "content": "Eleven young male Indian volunteers fasted overnight and were exposed to 6 h to cold at 8 degrees C (I), hypoxia at 4267 m at 28 degrees C (II), and cold plus hypoxia of 4267 m at , degrees C (III), in a walk-in climatic chamber, and excretion of some urinary constituents was measured. Urine output was significantly decreased in (II) and increased in (I) and (III). Urine pH significantly increased only in (II). Catecholamine excretion significantly increased only in (I). Ca++ excretion was significantly raised in (I) and (III) and lowered in (II). Na+ excretion was significantly decreased and K+ excretion remained unchanged in all three stress conditions. Cold seemed to be a greater stressor than hypoxia, under stated experimental conditions.", "contents": "Effects of 6 hours hypoxic and cold exposure on urinary electrolyte and catecholamine excretion. Eleven young male Indian volunteers fasted overnight and were exposed to 6 h to cold at 8 degrees C (I), hypoxia at 4267 m at 28 degrees C (II), and cold plus hypoxia of 4267 m at , degrees C (III), in a walk-in climatic chamber, and excretion of some urinary constituents was measured. Urine output was significantly decreased in (II) and increased in (I) and (III). Urine pH significantly increased only in (II). Catecholamine excretion significantly increased only in (I). Ca++ excretion was significantly raised in (I) and (III) and lowered in (II). Na+ excretion was significantly decreased and K+ excretion remained unchanged in all three stress conditions. Cold seemed to be a greater stressor than hypoxia, under stated experimental conditions."}
{"id": "PMID:23758", "title": "Detection after electrophoresis of enzymes involved in ammonia metabolism using L-glutamate dehydrogenase as a linking enzyme.", "content": "The use of L-glutamate dehydrogenase (GLUD) as a reagent in staining mixtures to detect the isozymes of enzymes which catalyze the production of ammonia has been investigated. Methods have been devised for the electrophoresis and detection, using GLUD, of seven enzymes: cytidine deaminase, adenosine deaminase, adenosine monophosphate deaminase, arginase, argininosuccinase, D-amino acid oxidase, and D-aspartate oxidase. GLUD-linked staining methods appear to be sensitive, specific, and of general application.", "contents": "Detection after electrophoresis of enzymes involved in ammonia metabolism using L-glutamate dehydrogenase as a linking enzyme. The use of L-glutamate dehydrogenase (GLUD) as a reagent in staining mixtures to detect the isozymes of enzymes which catalyze the production of ammonia has been investigated. Methods have been devised for the electrophoresis and detection, using GLUD, of seven enzymes: cytidine deaminase, adenosine deaminase, adenosine monophosphate deaminase, arginase, argininosuccinase, D-amino acid oxidase, and D-aspartate oxidase. GLUD-linked staining methods appear to be sensitive, specific, and of general application."}
{"id": "PMID:23759", "title": "Chemical modification of cellulase from Aspergillus niger.", "content": "N-Bromosuccinimide completely inactivated the cellulase, and titration experiments showed that oxidation of one tryptophan residue per cellulase molecule coincided with 100% inactivation. CM-cellulose protected the enzyme from inactivation by N-bromosuccinimide. The cellulase was inhibited by active benzyl halides, and reaction with 2-hydroxy-5-nitrobenzyl bromide resulted in the incorporation of 2.3 hydroxy-5-nitrobenzyl groups per enzyme molecule; one tryptophan residue was shown to be essential for activity. Diazocarbonyl compounds in the presence of Cu2+ ions inhibited the enzyme. The pH-dependence of inactivation was consistent with the reaction occurring with a protonated carboxyl group. Carbodi-imide inhibited the cellulase, and kinetic analysis indicated that there was an average of 1 mol of carbodi-imide binding to the cellulase during inactivation. Treatment of the cellulase with diethyl pyrocarbonate resulted in the modification of two out of the four histidine residues present in the cellulase. The modified enzyme retained 40% of its original activity. Inhibition of cellulase activity by the metal ions Ag+ and Hg2+ was ascribed to interaction with tryptophan residues, rather than with thiol groups.", "contents": "Chemical modification of cellulase from Aspergillus niger. N-Bromosuccinimide completely inactivated the cellulase, and titration experiments showed that oxidation of one tryptophan residue per cellulase molecule coincided with 100% inactivation. CM-cellulose protected the enzyme from inactivation by N-bromosuccinimide. The cellulase was inhibited by active benzyl halides, and reaction with 2-hydroxy-5-nitrobenzyl bromide resulted in the incorporation of 2.3 hydroxy-5-nitrobenzyl groups per enzyme molecule; one tryptophan residue was shown to be essential for activity. Diazocarbonyl compounds in the presence of Cu2+ ions inhibited the enzyme. The pH-dependence of inactivation was consistent with the reaction occurring with a protonated carboxyl group. Carbodi-imide inhibited the cellulase, and kinetic analysis indicated that there was an average of 1 mol of carbodi-imide binding to the cellulase during inactivation. Treatment of the cellulase with diethyl pyrocarbonate resulted in the modification of two out of the four histidine residues present in the cellulase. The modified enzyme retained 40% of its original activity. Inhibition of cellulase activity by the metal ions Ag+ and Hg2+ was ascribed to interaction with tryptophan residues, rather than with thiol groups."}
{"id": "PMID:23760", "title": "Changes in apparent pH on freezing aqueous buffer solutions and their relevance to biochemical electron-paramagnetic-resonance spectroscopy.", "content": "Changes in apparent pH occurring during fast freezing of aqueous buffer solutions and cooling to -196 degrees C were studied by various semiquantitative methods, including simple visual measurements of colour changes with pH indicators, as well as measurements of pH-dependent changes in the e.p.r. (electron paramagnetic resonance) spectra of solutions of three different metalloenzymes. It is concluded that apparent pH changes of up to about 3pH units may occur under particular conditions. Such changes were independent of the time taken to freeze the samples, when this was varied from about 3ms t0 20s, but were affected by the presence of some proteins in solution. Recommendations on the buffers that should be used to avoid such apparent pH changes in e.p.r. spectroscopy and other low-temperature biochemical work are made. Phosphate and pyrophosphate buffers, which gave large decreases (2-3 pH units), and Tris, which under some conditions gave increases of about the same magnitude, are to be avoided. Certain zwitterionic buffers such as Bicine [NN-bis-(2-hydroxyethyl)glycine] are satisfactory. Apparent pH effects were found to depend on buffer and protein concentration. It is therefore recommended that as a prelude to future detailed low-temperature biochemical work, appropriate tests with an indicator system should be performed.", "contents": "Changes in apparent pH on freezing aqueous buffer solutions and their relevance to biochemical electron-paramagnetic-resonance spectroscopy. Changes in apparent pH occurring during fast freezing of aqueous buffer solutions and cooling to -196 degrees C were studied by various semiquantitative methods, including simple visual measurements of colour changes with pH indicators, as well as measurements of pH-dependent changes in the e.p.r. (electron paramagnetic resonance) spectra of solutions of three different metalloenzymes. It is concluded that apparent pH changes of up to about 3pH units may occur under particular conditions. Such changes were independent of the time taken to freeze the samples, when this was varied from about 3ms t0 20s, but were affected by the presence of some proteins in solution. Recommendations on the buffers that should be used to avoid such apparent pH changes in e.p.r. spectroscopy and other low-temperature biochemical work are made. Phosphate and pyrophosphate buffers, which gave large decreases (2-3 pH units), and Tris, which under some conditions gave increases of about the same magnitude, are to be avoided. Certain zwitterionic buffers such as Bicine [NN-bis-(2-hydroxyethyl)glycine] are satisfactory. Apparent pH effects were found to depend on buffer and protein concentration. It is therefore recommended that as a prelude to future detailed low-temperature biochemical work, appropriate tests with an indicator system should be performed."}
{"id": "PMID:23761", "title": "Fungal degradation of aromatic nitriles. Enzymology of C-N cleavage by Fusarium solani.", "content": "1. A strain of the fungus Fusarium solani able to use benzonitrile as sole source of carbon and nitrogen was isolated by elective culture. 2. Respiration studies indicate that the nitrile, after degradation to benzoate, is catabolized via catechol or alternatively via p-hydroxybenzoate and 3,4-dihydroxybenzoate. 3. Cell-free extracts of benzonitrile-grown cells contain an enzyme mediating the conversion of benzonitrile into benzoate and ammonia. 4. The nitrilase enzyme was purified by DEAE-cellulose chromatography, (NH(4))(2)SO(4) precipitation and gel filtration on Sephadex G-200. The homogeneity of the purified enzyme preparation was confirmed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and isoelectric focusing on polyacrylamide gel. 5. The enzyme showed a broad pH optimum between pH7.8 and 9.1 and a K(m) with benzonitrile as substrate of 0.039mm. The activation energy of the reaction deduced from an Arrhenius plot was 48.4kJ/mol. 6. The enzyme was susceptible to inhibition by thiol-specific reagents and certain heavy metal ions. 7. Gel filtration gave a value of 620000 for the molecular weight of the intact enzyme. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis demonstrated that the enzyme was composed of eight subunits of mol.wt. 76000. 8. Rates of enzymic attack on various substrates indicated that the nitrilase has a fairly broad specificity and that the fungus probably plays an important role in the biodegradation of certain nitrilic herbicides in the environment.", "contents": "Fungal degradation of aromatic nitriles. Enzymology of C-N cleavage by Fusarium solani. 1. A strain of the fungus Fusarium solani able to use benzonitrile as sole source of carbon and nitrogen was isolated by elective culture. 2. Respiration studies indicate that the nitrile, after degradation to benzoate, is catabolized via catechol or alternatively via p-hydroxybenzoate and 3,4-dihydroxybenzoate. 3. Cell-free extracts of benzonitrile-grown cells contain an enzyme mediating the conversion of benzonitrile into benzoate and ammonia. 4. The nitrilase enzyme was purified by DEAE-cellulose chromatography, (NH(4))(2)SO(4) precipitation and gel filtration on Sephadex G-200. The homogeneity of the purified enzyme preparation was confirmed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and isoelectric focusing on polyacrylamide gel. 5. The enzyme showed a broad pH optimum between pH7.8 and 9.1 and a K(m) with benzonitrile as substrate of 0.039mm. The activation energy of the reaction deduced from an Arrhenius plot was 48.4kJ/mol. 6. The enzyme was susceptible to inhibition by thiol-specific reagents and certain heavy metal ions. 7. Gel filtration gave a value of 620000 for the molecular weight of the intact enzyme. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis demonstrated that the enzyme was composed of eight subunits of mol.wt. 76000. 8. Rates of enzymic attack on various substrates indicated that the nitrilase has a fairly broad specificity and that the fungus probably plays an important role in the biodegradation of certain nitrilic herbicides in the environment."}
{"id": "PMID:23762", "title": "The separation and characterization of marmoset kidney beta-D-galactosidase and beta-D-glucosidase.", "content": "beta-D-Galactosidase and beta-D-glucosidase activities were determined in homogenates of marmoset kidney by using the appropriate 4-methylumbelliferyl glycoside, beta-D-Galactosidase activity was separated into two main components by ion-exchange chromatography on DEAE-cellulose, starch-gel electrophoresis, isoelectric focusing and gel filtration on Sephadex G-200. One form designated A had a pI of 5.1, was loosely bound to DEAE-cellulose at pH7.0, remained near the origin on starch-gel electrophoresis at pH 7.0 and had an apparent molecular weight of 160000. The second beta-D-galactosidase component, designated B, was associated with the total beta-D-glucosidase activity, had a pI of 4.3, was firmly bound to DEAE-cellulose, migrated rapidly towards the anode on starch-gel electrophoresis and had an apparent molecular weight of 50000. The optimum pH values of beta-D-galactosidase A and B were 4.5 and 6.0 respectively. beta-D-Galactosidase A was activated by 0.1 M-NaC1 but the activity of the B form was inhibited by 1 M-NaC1 at pH 4.5. beta-D-galactosidase had a bimodal distribution, the A form being recovered in the lysosomal fraction whereas the B form was present in the soluble fraction, as was the major portion of the beta-D-glucosidase activity. The lysosomal and soluble forms were further characterized by DEAE-cellulose chromatography.", "contents": "The separation and characterization of marmoset kidney beta-D-galactosidase and beta-D-glucosidase. beta-D-Galactosidase and beta-D-glucosidase activities were determined in homogenates of marmoset kidney by using the appropriate 4-methylumbelliferyl glycoside, beta-D-Galactosidase activity was separated into two main components by ion-exchange chromatography on DEAE-cellulose, starch-gel electrophoresis, isoelectric focusing and gel filtration on Sephadex G-200. One form designated A had a pI of 5.1, was loosely bound to DEAE-cellulose at pH7.0, remained near the origin on starch-gel electrophoresis at pH 7.0 and had an apparent molecular weight of 160000. The second beta-D-galactosidase component, designated B, was associated with the total beta-D-glucosidase activity, had a pI of 4.3, was firmly bound to DEAE-cellulose, migrated rapidly towards the anode on starch-gel electrophoresis and had an apparent molecular weight of 50000. The optimum pH values of beta-D-galactosidase A and B were 4.5 and 6.0 respectively. beta-D-Galactosidase A was activated by 0.1 M-NaC1 but the activity of the B form was inhibited by 1 M-NaC1 at pH 4.5. beta-D-galactosidase had a bimodal distribution, the A form being recovered in the lysosomal fraction whereas the B form was present in the soluble fraction, as was the major portion of the beta-D-glucosidase activity. The lysosomal and soluble forms were further characterized by DEAE-cellulose chromatography."}
{"id": "PMID:23763", "title": "Proteoglycan-degrading enzymes. A radiochemical assay method and the detection of a new enzyme cathepsin F.", "content": "1. Polyacrylamide beads containing entrapped 35S-labelled proteoglycan molecules have been prepared. 2. The measurement of release of radioactivity provides an extremely sensitive assay for proteoglycan-degrading enzymes, including proteinases and hyaluronidase. 3. The amount of label released is a logarithmic function of enzyme concentration or time of incubation. Experiments were made in an attempt to explain this. 4. Assays were made by the new method at several pH values, and with the inclusion of inhibitors to identify the proteoglycan-degrading enzymes of rabbit ear cartilage. 5. A previously undescribed proteinase active against proteoglycan at pH4.5 but unaffected by pepstatin, was discovered. The enzyme was named cathepsin F, and was partially purified and characterized; it was detected in human articular cartilage.", "contents": "Proteoglycan-degrading enzymes. A radiochemical assay method and the detection of a new enzyme cathepsin F. 1. Polyacrylamide beads containing entrapped 35S-labelled proteoglycan molecules have been prepared. 2. The measurement of release of radioactivity provides an extremely sensitive assay for proteoglycan-degrading enzymes, including proteinases and hyaluronidase. 3. The amount of label released is a logarithmic function of enzyme concentration or time of incubation. Experiments were made in an attempt to explain this. 4. Assays were made by the new method at several pH values, and with the inclusion of inhibitors to identify the proteoglycan-degrading enzymes of rabbit ear cartilage. 5. A previously undescribed proteinase active against proteoglycan at pH4.5 but unaffected by pepstatin, was discovered. The enzyme was named cathepsin F, and was partially purified and characterized; it was detected in human articular cartilage."}
{"id": "PMID:23764", "title": "Steady-state kinetic studies of the negative co-operativity and flip-flop mechanism for Escherichia coli alkaline phosphatase.", "content": "1. A study of variations in experimental error of velocity measurement with substrate concentration for alkaline phosphatase reveals that the standard error is not constant or strictly proportional to velocity, but obeys a more complex dependence. 2. By using an approach based on error estimates at each individual substrate concentration, we show that the double-reciprocal plots in general are curved, necessitating a high-degree rate equation. The curves are analysed according to a recent classification of possible curve shapes for the 3:3 function, which is shown to be the lowest-degree rate equation satisfying the experimental data. 4. Other workers have supposed the enzyme to follow Michaelis-Menten kinetics, and it is shown that this assumption is approximately true at low temperatures in the absence of phosphate. 5. A study of the effects of phosphate concentration, pH and temperature on the kinetics shows that there is a gradual alteration in curve shape with these experimental variables, resulting in an apparent reduction in degree under certain special conditions, and particularly at low temperature. 6. It is shown that the steady-state kinetics do not require a flip-flop or half-of-sites reactivity mechanism as claimed, and a mechanism is proposed, a rate equation calculated and an analysis attempted. 7. An analysis of the product-inhibition effects for a linked two-sited Uni Bi enzyme is given. Alterations of asymptotic double-reciprocal slopes and limiting (1/nu) intercepts with products is discussed, and it is shown how the theory of product inhibition can be extended to complex kinetic situations to extract information as to molecular mechanism. 8. Deviations from Michaelis-Menten kinetics are expressed in terms of the magnitude of the appropriate Sylvester resultants.", "contents": "Steady-state kinetic studies of the negative co-operativity and flip-flop mechanism for Escherichia coli alkaline phosphatase. 1. A study of variations in experimental error of velocity measurement with substrate concentration for alkaline phosphatase reveals that the standard error is not constant or strictly proportional to velocity, but obeys a more complex dependence. 2. By using an approach based on error estimates at each individual substrate concentration, we show that the double-reciprocal plots in general are curved, necessitating a high-degree rate equation. The curves are analysed according to a recent classification of possible curve shapes for the 3:3 function, which is shown to be the lowest-degree rate equation satisfying the experimental data. 4. Other workers have supposed the enzyme to follow Michaelis-Menten kinetics, and it is shown that this assumption is approximately true at low temperatures in the absence of phosphate. 5. A study of the effects of phosphate concentration, pH and temperature on the kinetics shows that there is a gradual alteration in curve shape with these experimental variables, resulting in an apparent reduction in degree under certain special conditions, and particularly at low temperature. 6. It is shown that the steady-state kinetics do not require a flip-flop or half-of-sites reactivity mechanism as claimed, and a mechanism is proposed, a rate equation calculated and an analysis attempted. 7. An analysis of the product-inhibition effects for a linked two-sited Uni Bi enzyme is given. Alterations of asymptotic double-reciprocal slopes and limiting (1/nu) intercepts with products is discussed, and it is shown how the theory of product inhibition can be extended to complex kinetic situations to extract information as to molecular mechanism. 8. Deviations from Michaelis-Menten kinetics are expressed in terms of the magnitude of the appropriate Sylvester resultants."}
{"id": "PMID:23765", "title": "Benzofuroxan as a thiol-specific reactivity probe. Kinetics of its reactions with papain, ficin, bromelain and low-molecular-weight thiols.", "content": "1. The characteristics of benzofuroxan (benzofurazan 1-oxide, benzo-2-oxa-1,3-diazole N-oxide) that relate to its application as a reactivity probe for the study of environments of thiol groups are discussed. 2. To establish a kinetic and mechanistic basis for its use as a probe, a kinetic study of its reaction with 2-mercaptoethanol was carried out. 3. This reaction appears to proceed by a rate-determining attack of the thiolate ion on one of the electrophilic centres of benzofuroxan (possibly C-6) to provide a low steady-state concentration of an intermediate adduct; rapid reaction of this adduct with a second molecule of thiol gives the disulphide and o-benzoquinone dioxime. 4. The effects of the different types of environment that proteins can provide on the kinetic characteristics of reactions of thiol groups with benzofuroxan are delineated. 5. Benzofuroxan was used as a thiolspecific reactivity probe to investigate the active centres of papain (EC 3.4.22.2), ficin (EC 3.4.22.3) and bromelain (EC 3.4.22.4). The results support the concept that the active centres of all three enzymes either contain a nucleophilic thiolate ion whose formation is characterized by a pKa of 3-4 and whose reaction with an electrophile can be assisted by interaction of a site of high electron density in the electrophile with active-centre imidazolium ion of pKa 8-9, or can provide such ions by protonic redistribution in enzyme-reagent or enzyme-substrate complexes.", "contents": "Benzofuroxan as a thiol-specific reactivity probe. Kinetics of its reactions with papain, ficin, bromelain and low-molecular-weight thiols. 1. The characteristics of benzofuroxan (benzofurazan 1-oxide, benzo-2-oxa-1,3-diazole N-oxide) that relate to its application as a reactivity probe for the study of environments of thiol groups are discussed. 2. To establish a kinetic and mechanistic basis for its use as a probe, a kinetic study of its reaction with 2-mercaptoethanol was carried out. 3. This reaction appears to proceed by a rate-determining attack of the thiolate ion on one of the electrophilic centres of benzofuroxan (possibly C-6) to provide a low steady-state concentration of an intermediate adduct; rapid reaction of this adduct with a second molecule of thiol gives the disulphide and o-benzoquinone dioxime. 4. The effects of the different types of environment that proteins can provide on the kinetic characteristics of reactions of thiol groups with benzofuroxan are delineated. 5. Benzofuroxan was used as a thiolspecific reactivity probe to investigate the active centres of papain (EC 3.4.22.2), ficin (EC 3.4.22.3) and bromelain (EC 3.4.22.4). The results support the concept that the active centres of all three enzymes either contain a nucleophilic thiolate ion whose formation is characterized by a pKa of 3-4 and whose reaction with an electrophile can be assisted by interaction of a site of high electron density in the electrophile with active-centre imidazolium ion of pKa 8-9, or can provide such ions by protonic redistribution in enzyme-reagent or enzyme-substrate complexes."}
{"id": "PMID:23766", "title": "Degradation of myofibrillar proteins by cathepsins B and D.", "content": "1. The procedure of Barrett [(1973) Biochem. J.131, 809-822] for isolating cathepsins B and D from human liver was modified for use with rat liver and skeletal muscle. The purified enzymes appeared to be similar to those reported in other species. 2. Sephadex G-75 chromatography of concentrated muscle extract resolved two peaks of cathepsin B inhibitory activity, corresponding to molecular weights of 12500 and 62000. 3. The degradation of purified myofibrillar proteins by cathepsins B and D was clearly demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. After incubation with enzyme, the polypeptide bands representing the substrates decreased in intensity and lower molecular weight products appeared. 4. Cathepsins B and D, purified from either rat liver or skeletal muscle, were shown to degrade myosin, purified from either rabbit or rat muscle. Soluble denatured myosin was degraded more extensively than insoluble native myosin. Degradation by cathepsin B was inhibited by lack of reducing agent, or by myoglobin, iodoacetic acid and leupeptin, but not by pepstatin. The same potential modifiers were applied to cathepsin D, and only pepstatin produced inhibition. 5. Rat liver cathepsin B had a pH optimum of 5.2 on native rabbit myosin. The pH optimum of cathepsin D was 4.0, with a shoulder of activity about 1pH unit above the optimum. 6. Rat liver cathepsins B and D were demonstrated to degrade rabbit F-actin at pH5.0, and were inhibited by leupeptin and pepstain, respectively. 7. The degradation of myosin and actin by cathepsin D was more extensive than that by cathepsin B.", "contents": "Degradation of myofibrillar proteins by cathepsins B and D. 1. The procedure of Barrett [(1973) Biochem. J.131, 809-822] for isolating cathepsins B and D from human liver was modified for use with rat liver and skeletal muscle. The purified enzymes appeared to be similar to those reported in other species. 2. Sephadex G-75 chromatography of concentrated muscle extract resolved two peaks of cathepsin B inhibitory activity, corresponding to molecular weights of 12500 and 62000. 3. The degradation of purified myofibrillar proteins by cathepsins B and D was clearly demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. After incubation with enzyme, the polypeptide bands representing the substrates decreased in intensity and lower molecular weight products appeared. 4. Cathepsins B and D, purified from either rat liver or skeletal muscle, were shown to degrade myosin, purified from either rabbit or rat muscle. Soluble denatured myosin was degraded more extensively than insoluble native myosin. Degradation by cathepsin B was inhibited by lack of reducing agent, or by myoglobin, iodoacetic acid and leupeptin, but not by pepstatin. The same potential modifiers were applied to cathepsin D, and only pepstatin produced inhibition. 5. Rat liver cathepsin B had a pH optimum of 5.2 on native rabbit myosin. The pH optimum of cathepsin D was 4.0, with a shoulder of activity about 1pH unit above the optimum. 6. Rat liver cathepsins B and D were demonstrated to degrade rabbit F-actin at pH5.0, and were inhibited by leupeptin and pepstain, respectively. 7. The degradation of myosin and actin by cathepsin D was more extensive than that by cathepsin B."}
{"id": "PMID:23767", "title": "The active site of beta-glucosidase from Botryodiplodia theobromae. Effects of pH and dioxan on enzyme-catalysed reactions.", "content": "1. The hydrolysis of o-nitrophenyl beta-D-glucopyranoside by the high-molecular-weight beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) of Botryodiplodia theobromae Pat in the absence or presence of added dioxan was found to be dependent on the ionization of two groups, which appeared to be a carboxyl group and an imidazole group. 2. Dioxan increased the Michaelis constant, Km, but decreased the maximum velocity, V.", "contents": "The active site of beta-glucosidase from Botryodiplodia theobromae. Effects of pH and dioxan on enzyme-catalysed reactions. 1. The hydrolysis of o-nitrophenyl beta-D-glucopyranoside by the high-molecular-weight beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) of Botryodiplodia theobromae Pat in the absence or presence of added dioxan was found to be dependent on the ionization of two groups, which appeared to be a carboxyl group and an imidazole group. 2. Dioxan increased the Michaelis constant, Km, but decreased the maximum velocity, V."}
{"id": "PMID:23768", "title": "Phospholipase A activity associated with membranes of human polymorphonuclear leucocytes.", "content": "Homogenates of human polymorphonuclear leucocytes (granulocytes) contain a Ca2+-dependent phospholipase A with optimal activity pH7.0. This enzyme is membrane-bound and is enriched in crude cytoplasmic-granule fraction. Ratezonal centrifugation of the cytoplasmic-granule fraction demonstrates that the phospholipase A is associated not only with specific- and azurophilic-granule populations but also with an 'empty' vesicular fraction containing 85% of the total alkaline phosphatase activity of whole homogenate. Thus this phospholipase is associated with granule as well as with other cellular membranes of human granulocytes.", "contents": "Phospholipase A activity associated with membranes of human polymorphonuclear leucocytes. Homogenates of human polymorphonuclear leucocytes (granulocytes) contain a Ca2+-dependent phospholipase A with optimal activity pH7.0. This enzyme is membrane-bound and is enriched in crude cytoplasmic-granule fraction. Ratezonal centrifugation of the cytoplasmic-granule fraction demonstrates that the phospholipase A is associated not only with specific- and azurophilic-granule populations but also with an 'empty' vesicular fraction containing 85% of the total alkaline phosphatase activity of whole homogenate. Thus this phospholipase is associated with granule as well as with other cellular membranes of human granulocytes."}
{"id": "PMID:23769", "title": "The pH-dependence of second-order rate constants of enzyme modification may provide free-reactant pKa values.", "content": "1. Reactions of enzymes with site-specific reagents may involve intermediate adsorptive complexes formed by parallel reactions in several protonic states. Accordingly, a profile of the apparent second-order rate constant for the modification reaction (Kobs., the observed rate constant under conditions where the reagent concentration is low enough for the reaction to be first-order in reagent) against pH can, in general, reflect free-reactant-state molecular pKa values only if a quasi-equilibrium condition exists around the reactive protonic state (EHR) of the adsorptive complex. 2. Usually the condition for quasi-equilibrium is expressed in terms of the rate constants around EHR: (formula: see text) i.e. k mod. less than k-2. This often cannot be assessed directly, particularly if it is not possible to determine kmod. 3. It is shown that kmod. must be much less than k-2, however, if kobs. (the pH-independent value of kobs.) less than k+2. 4. Since probable values of k+2 greater than 10(6)M-1.S-1 and since values of kobs. for many modification reactions less than 10(6)M-1.S-1, the equilibrium assumption should be valid, and kinetic study of such reactions should provide reactant-state pKa values. 5. This may not apply to catalyses, because for them the value of kcat./Km may exceed 5 X 10(5)M-1.S-1. 6. The conditions under which the formation of an intermediate complex by parallel pathways may come to quasi-equilibrium are discussed in the Appendix.", "contents": "The pH-dependence of second-order rate constants of enzyme modification may provide free-reactant pKa values. 1. Reactions of enzymes with site-specific reagents may involve intermediate adsorptive complexes formed by parallel reactions in several protonic states. Accordingly, a profile of the apparent second-order rate constant for the modification reaction (Kobs., the observed rate constant under conditions where the reagent concentration is low enough for the reaction to be first-order in reagent) against pH can, in general, reflect free-reactant-state molecular pKa values only if a quasi-equilibrium condition exists around the reactive protonic state (EHR) of the adsorptive complex. 2. Usually the condition for quasi-equilibrium is expressed in terms of the rate constants around EHR: (formula: see text) i.e. k mod. less than k-2. This often cannot be assessed directly, particularly if it is not possible to determine kmod. 3. It is shown that kmod. must be much less than k-2, however, if kobs. (the pH-independent value of kobs.) less than k+2. 4. Since probable values of k+2 greater than 10(6)M-1.S-1 and since values of kobs. for many modification reactions less than 10(6)M-1.S-1, the equilibrium assumption should be valid, and kinetic study of such reactions should provide reactant-state pKa values. 5. This may not apply to catalyses, because for them the value of kcat./Km may exceed 5 X 10(5)M-1.S-1. 6. The conditions under which the formation of an intermediate complex by parallel pathways may come to quasi-equilibrium are discussed in the Appendix."}
{"id": "PMID:23790", "title": "[Effect of the beta-adrenergic blocking agent bupranolol on the plasma renin activity in normotensive rats].", "content": "The effects of the beta-adrenergic blocking agent 3-tert.-butyl-amino-1-(6'-chloro-3'-methylphenoxy)-propan-2-ol hydrochloride (bupranolol; KL 255; Betadrenol) on the plasma renin activity (PRA) of normotensive rats were studied in comparison to propranolol. Bupranolol (10--100 microgram/kg) reduced basal PRA and inhibited the isoproterenol as well as dihydralazine induced increase of PRA in a dose dependent fashion. Bupranolol exhibited an effect 2--4 times stronger than that of propranolol. The PRA inhibiting effects of bupranolol seem to be linked to its beta-receptor blocking properties.", "contents": "[Effect of the beta-adrenergic blocking agent bupranolol on the plasma renin activity in normotensive rats]. The effects of the beta-adrenergic blocking agent 3-tert.-butyl-amino-1-(6'-chloro-3'-methylphenoxy)-propan-2-ol hydrochloride (bupranolol; KL 255; Betadrenol) on the plasma renin activity (PRA) of normotensive rats were studied in comparison to propranolol. Bupranolol (10--100 microgram/kg) reduced basal PRA and inhibited the isoproterenol as well as dihydralazine induced increase of PRA in a dose dependent fashion. Bupranolol exhibited an effect 2--4 times stronger than that of propranolol. The PRA inhibiting effects of bupranolol seem to be linked to its beta-receptor blocking properties."}
{"id": "PMID:23791", "title": "Effect of halopredone acetate on rat liver tryptophan oxygenase and tyrosine aminotransferase activities.", "content": "The possible inductive effect of a new local antiinflammatory steroid, 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon), on the rat liver enzymes tryptophan oxygenase and tyrosine aminotransferase was evaluated. The new steroid, when present in the implanted cotton-pellets or when s.c. injected, unlike the reference compound, fluocinolone acetonide, which induced a large increase in both enzymes, did not modify either tryptophan oxygenase or tyrosine aminotransferase. The results confirm that halopredone acetate elicits potent local antiinflammatory activity in the absence of systemic effects.", "contents": "Effect of halopredone acetate on rat liver tryptophan oxygenase and tyrosine aminotransferase activities. The possible inductive effect of a new local antiinflammatory steroid, 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon), on the rat liver enzymes tryptophan oxygenase and tyrosine aminotransferase was evaluated. The new steroid, when present in the implanted cotton-pellets or when s.c. injected, unlike the reference compound, fluocinolone acetonide, which induced a large increase in both enzymes, did not modify either tryptophan oxygenase or tyrosine aminotransferase. The results confirm that halopredone acetate elicits potent local antiinflammatory activity in the absence of systemic effects."}
{"id": "PMID:23788", "title": "Drugs affecting the release of rheumatoid factor in a plaque-forming cell assay.", "content": "Addition of propranolol to the agarose phase of a plaque-forming cell (PFC) assay for rheumatoid factor (RF) caused reduction in the number of plaques seen. This reduction in rheumatoid factor plaque-forming cell (RF PFC) did not depend upon an effect at the beta-adrenergic receptor, since d- and 1-propranolol reduced equally well. Furthermore, in a series of polycyclic compounds with varying beta-receptor blocking capabilities there was no agreement between plaque reduction and blocking. When propranolol was tested in the agarose in an anti-sheep erythrocyte (SRC) plaque assay (anti-SRC PFC), it had no inhibitory effect, but it was capable of inhibiting the generation of new anti-SRC PFC in an in vitro culture. Propranolol is thought to exert these effects through its membrane stabilizing (anesthetic) properties.", "contents": "Drugs affecting the release of rheumatoid factor in a plaque-forming cell assay. Addition of propranolol to the agarose phase of a plaque-forming cell (PFC) assay for rheumatoid factor (RF) caused reduction in the number of plaques seen. This reduction in rheumatoid factor plaque-forming cell (RF PFC) did not depend upon an effect at the beta-adrenergic receptor, since d- and 1-propranolol reduced equally well. Furthermore, in a series of polycyclic compounds with varying beta-receptor blocking capabilities there was no agreement between plaque reduction and blocking. When propranolol was tested in the agarose in an anti-sheep erythrocyte (SRC) plaque assay (anti-SRC PFC), it had no inhibitory effect, but it was capable of inhibiting the generation of new anti-SRC PFC in an in vitro culture. Propranolol is thought to exert these effects through its membrane stabilizing (anesthetic) properties."}
{"id": "PMID:23792", "title": "[Studies on Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide). Part 1: Physico-chemical and chemical properties (author's transl)].", "content": "The saluretic agent xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide; Aquaphor) is a lipophilic substance as demonstrated by solubilities and partition coefficients. In the physiological pH-range, however, xipamide forms an anion which has an octanol-water partition coefficient of approx. 1. Two steps of ionization were investigated photometrically. The first one gives rise to a phenolate anion; pKa1 = 4.75. In the second one, ionization of the sulfamoyl group occurs; pKa2 = 10. Xipamide is stable in acidic as well as in basic media at room temperature. But when xipamide is acted upon by strong alkali and elevated temperature, 2,6-xylidine is formed by hydrolysis. For analytic use UV-photometric, colorimetric and TLC data of xipamide are given.", "contents": "[Studies on Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide). Part 1: Physico-chemical and chemical properties (author's transl)]. The saluretic agent xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide; Aquaphor) is a lipophilic substance as demonstrated by solubilities and partition coefficients. In the physiological pH-range, however, xipamide forms an anion which has an octanol-water partition coefficient of approx. 1. Two steps of ionization were investigated photometrically. The first one gives rise to a phenolate anion; pKa1 = 4.75. In the second one, ionization of the sulfamoyl group occurs; pKa2 = 10. Xipamide is stable in acidic as well as in basic media at room temperature. But when xipamide is acted upon by strong alkali and elevated temperature, 2,6-xylidine is formed by hydrolysis. For analytic use UV-photometric, colorimetric and TLC data of xipamide are given."}
{"id": "PMID:23793", "title": "Camazepam versus placebo. A double-blind clinical study on geriatric patients suffering from psychic complaints. Short Communication.", "content": "Camazepam, a dimethylcarbamic derivative of benzodiazepines, was studied on forty geriatric in-patients suffering from psychic disorders concerning anxiety and depression. Patients were treated with placebo and 30 mg of camazepam per day for 20 days using the double-blind method. The patients were assessed using a simplified rating scale with target symptoms of anxiety and depression. Statistical evaluation was performed with general Student's t-test for paired samples and chi2 test. Both groups of patients improved with camazepam and placebo. Camazepam 30 mg per day was more effective than placebo to a statistically significant degree.", "contents": "Camazepam versus placebo. A double-blind clinical study on geriatric patients suffering from psychic complaints. Short Communication. Camazepam, a dimethylcarbamic derivative of benzodiazepines, was studied on forty geriatric in-patients suffering from psychic disorders concerning anxiety and depression. Patients were treated with placebo and 30 mg of camazepam per day for 20 days using the double-blind method. The patients were assessed using a simplified rating scale with target symptoms of anxiety and depression. Statistical evaluation was performed with general Student's t-test for paired samples and chi2 test. Both groups of patients improved with camazepam and placebo. Camazepam 30 mg per day was more effective than placebo to a statistically significant degree."}
{"id": "PMID:23794", "title": "Synthetic MIF analogues. Part I: synthesis by four-component condensation (4 CC) and classical methods.", "content": "Analogues of melanocyte stimulating hormone/release inhibiting hormone (MIF), H-Pro-N-isobutyl-Gly-Gly-NH2, H-Pro-MeLeu-Gly-NH2 (L,L) and H-Pro-MeLeu-Gly-NH2 (L,D) were synthesized by the four-component condensation (4 CC). In addition compounds H-Pro-MeLeu-Ala-NH2 (L,L,D) and H-Pro-MeLeu-Ala-NH2 (L,D,D) were prepared by classical methods.", "contents": "Synthetic MIF analogues. Part I: synthesis by four-component condensation (4 CC) and classical methods. Analogues of melanocyte stimulating hormone/release inhibiting hormone (MIF), H-Pro-N-isobutyl-Gly-Gly-NH2, H-Pro-MeLeu-Gly-NH2 (L,L) and H-Pro-MeLeu-Gly-NH2 (L,D) were synthesized by the four-component condensation (4 CC). In addition compounds H-Pro-MeLeu-Ala-NH2 (L,L,D) and H-Pro-MeLeu-Ala-NH2 (L,D,D) were prepared by classical methods."}
{"id": "PMID:23795", "title": "Synthetic MIF analogues. Part II: Dopa potentiation and fluphenazine antagonism.", "content": "A comparison is described between the activity of the melanocyte-stimulating hormone release inhibiting factor (MIF) and those of five synthetic tripeptide analogues of MIF. The comparison was based upon the ability of the compounds to potentiate the behavioral effects of L-dopa in mide and to antagonize fluphenazine-induced catalepsy in rats. Three of the tripeptides potentiated L-dopa in a manner similar to that of MIF. All of the synthetic analogues antagonized fluphenazine after a single dose although their potency and their duration of action differed. MIF was active in the latter test only following chronic administration. The possible mechanism of action and the potential clinical applicability of the tripeptides are briefly discussed.", "contents": "Synthetic MIF analogues. Part II: Dopa potentiation and fluphenazine antagonism. A comparison is described between the activity of the melanocyte-stimulating hormone release inhibiting factor (MIF) and those of five synthetic tripeptide analogues of MIF. The comparison was based upon the ability of the compounds to potentiate the behavioral effects of L-dopa in mide and to antagonize fluphenazine-induced catalepsy in rats. Three of the tripeptides potentiated L-dopa in a manner similar to that of MIF. All of the synthetic analogues antagonized fluphenazine after a single dose although their potency and their duration of action differed. MIF was active in the latter test only following chronic administration. The possible mechanism of action and the potential clinical applicability of the tripeptides are briefly discussed."}
{"id": "PMID:23796", "title": "Synthetic melanocyte stimulating hormone release-inhibiting factor (MIF). Part III: effect of L-prolyl-N-methyl-D-leucyl-glycinamide and MIF on biogenic amine turnover.", "content": "The effect of the factor that inhibits the release of melanocyte stimulating hormone (MSH), i.e., L-prolyl-L-leucyl-glycinamide (MIF), and L-prolyl-N-methyl-D-leucyl-glycinamide, an analog, on brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) turnover was examined in rats. The analog (40 mg/kg i.p.), in a fashion similar to MIF (40 and 5 mg/kg i.p.), increased brain DA turnover; only MIF (40 mg/kg i.p.) increased endogenous DA levels. The analog (40 and 5 mg/kg i.p.) decreased brain NE turnover; MIF at the same doses was ineffective. Neither MIF nor the analog affected rat brain 5-HT turnover or the 5-HTP-induced behavioural syndrome in the mouse. These results indicate that the analog, like MIF, exerts effects on central catecholamine turnover. The different biochemical profile of the analog compared to MIF may be importance with regard to potential clinical use in the treatment of Parkinson's disease and depression.", "contents": "Synthetic melanocyte stimulating hormone release-inhibiting factor (MIF). Part III: effect of L-prolyl-N-methyl-D-leucyl-glycinamide and MIF on biogenic amine turnover. The effect of the factor that inhibits the release of melanocyte stimulating hormone (MSH), i.e., L-prolyl-L-leucyl-glycinamide (MIF), and L-prolyl-N-methyl-D-leucyl-glycinamide, an analog, on brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) turnover was examined in rats. The analog (40 mg/kg i.p.), in a fashion similar to MIF (40 and 5 mg/kg i.p.), increased brain DA turnover; only MIF (40 mg/kg i.p.) increased endogenous DA levels. The analog (40 and 5 mg/kg i.p.) decreased brain NE turnover; MIF at the same doses was ineffective. Neither MIF nor the analog affected rat brain 5-HT turnover or the 5-HTP-induced behavioural syndrome in the mouse. These results indicate that the analog, like MIF, exerts effects on central catecholamine turnover. The different biochemical profile of the analog compared to MIF may be importance with regard to potential clinical use in the treatment of Parkinson's disease and depression."}
{"id": "PMID:23797", "title": "beta-adrenoceptor blockade with diphenylhydantoin (DPH).", "content": "Diphenylhydantoin (DPH) (20 x 10(-6) to 80 x 10(-6) M/kg) blocked the depressor responses to isoproterenol in spinal, bilaterally vagotomized and atropine pretreated cats; depressor responses to histamine were unaffected; DPH shifted the isoproterenol concentration-response curve to the right in isolated guinea pig tracheal chain preparation, isolated rabbit ileum and isolated perfused heart of frog. The results suggest that DPH has a specific beta-adrenoceptor blocking action and the blockade appears to be competitive in nature as shown by PA2 and PA10 values.", "contents": "beta-adrenoceptor blockade with diphenylhydantoin (DPH). Diphenylhydantoin (DPH) (20 x 10(-6) to 80 x 10(-6) M/kg) blocked the depressor responses to isoproterenol in spinal, bilaterally vagotomized and atropine pretreated cats; depressor responses to histamine were unaffected; DPH shifted the isoproterenol concentration-response curve to the right in isolated guinea pig tracheal chain preparation, isolated rabbit ileum and isolated perfused heart of frog. The results suggest that DPH has a specific beta-adrenoceptor blocking action and the blockade appears to be competitive in nature as shown by PA2 and PA10 values."}
{"id": "PMID:23798", "title": "Experiments in animals on the pharmacological effects of metipranolol in comparison with propranolol and pindolol.", "content": "The beta-blocking agent 1-(4-acetoxy-2,3,5-trimethylphenyloxy)-3-isopropylamino-propan-2-ol (metipranolol) was compared with propranolol and pindolol. The beta-blocking activity on isoproterenol induced tachycardia was determined in rabbits (ED250bpm). The following doses in microgram/kg i.v. were required to produce the same inhibition: 410 propranolol; 160 metipranolol; 130 pindolol. When intrinsic sympathomimetic activity was determined in reserpinized rats metipranolol was found to produce less than 10% of the increase in heart rate induced by a standard isoproterenol dose (1 mg/kg i.p.), whereas propranolol caused less than 20% and pindolol ca. 60%. The membrane stabilising activity, determined by the elevation of the fibrillation threshold (ED delta100muA) in rabbit hearts, was found to be greatest with propranolol (0.98 mg/kg i.v.) and least with metipranolol (1.68 mg/kg), with pindolol occupying an intermediate position (1.10 mg/kg). The cardioprotective action to hypoxia stress of metipranolol in rats was found to be the best, requiring a dose of only 5 microgram/kg i.p. compared with values of 28 microgram/kg for pindolol and 250 microgram/kg for propranolol. These results show that metipranolol has a high beta-sympatholytic activity which is not accompanied by either marked intrinsic activity or membrane-stabilising properties. The relatively marked cardioprotective action, which is probably due to a metabolic action, is particularly noteworthy.", "contents": "Experiments in animals on the pharmacological effects of metipranolol in comparison with propranolol and pindolol. The beta-blocking agent 1-(4-acetoxy-2,3,5-trimethylphenyloxy)-3-isopropylamino-propan-2-ol (metipranolol) was compared with propranolol and pindolol. The beta-blocking activity on isoproterenol induced tachycardia was determined in rabbits (ED250bpm). The following doses in microgram/kg i.v. were required to produce the same inhibition: 410 propranolol; 160 metipranolol; 130 pindolol. When intrinsic sympathomimetic activity was determined in reserpinized rats metipranolol was found to produce less than 10% of the increase in heart rate induced by a standard isoproterenol dose (1 mg/kg i.p.), whereas propranolol caused less than 20% and pindolol ca. 60%. The membrane stabilising activity, determined by the elevation of the fibrillation threshold (ED delta100muA) in rabbit hearts, was found to be greatest with propranolol (0.98 mg/kg i.v.) and least with metipranolol (1.68 mg/kg), with pindolol occupying an intermediate position (1.10 mg/kg). The cardioprotective action to hypoxia stress of metipranolol in rats was found to be the best, requiring a dose of only 5 microgram/kg i.p. compared with values of 28 microgram/kg for pindolol and 250 microgram/kg for propranolol. These results show that metipranolol has a high beta-sympatholytic activity which is not accompanied by either marked intrinsic activity or membrane-stabilising properties. The relatively marked cardioprotective action, which is probably due to a metabolic action, is particularly noteworthy."}
{"id": "PMID:23799", "title": "[Elucidation of the mechanism of nicotinic acid flush in the animal experiment (author's transl)].", "content": "The reddening of the ears of guinea pigs following the administration of nicotinic acid and its derivatives is regarded as an animal experiment for the human flush-reaction. In agreement with the observations in humans we found that the reddening effects decreased after repeated administration of xantinol nicotinate (Complamin). The results demonstrate that the reddening of the ears of guinea pigs--and presumably flushing in humans as well--is a complex event. The liberation of prostaglandins, histamine and serotonin, and first of all, cholinergic reactions, seem to be involved.", "contents": "[Elucidation of the mechanism of nicotinic acid flush in the animal experiment (author's transl)]. The reddening of the ears of guinea pigs following the administration of nicotinic acid and its derivatives is regarded as an animal experiment for the human flush-reaction. In agreement with the observations in humans we found that the reddening effects decreased after repeated administration of xantinol nicotinate (Complamin). The results demonstrate that the reddening of the ears of guinea pigs--and presumably flushing in humans as well--is a complex event. The liberation of prostaglandins, histamine and serotonin, and first of all, cholinergic reactions, seem to be involved."}
{"id": "PMID:23800", "title": "Metabolic fate of carteolol hydrochloride, (OPC-1085) VIII, a new beta-adrenergic blocking agent. Pharmacokinetic studies of carteolol in man.", "content": "The pharmacokinetics of 5-(3-tert.-butylamino-2-hydroxy)-propoxy-3,4-dihydrocarbostyril hydrochloride (carteolol hydrochloride, OPC-1085) have been investigated in man following single or repetitive oral administration. The plasma half-lives. The plasma half-lives of carteolol at single doses of 10, 15 and 30 mg were 5.4, 5.5 and 5.0 h, respectively. The amounts of carteolol excreted into urine within 24 h at the same dose levels accounted for 64, 70 and 76% of the respective doses. The half-lives obtained by the Sigmaminus method were 5.6, 5.6 and 5.4 h, respectively, being essentially consistent with the aforementioned plasma half-lives of carteolol after administration at 15 mg daily for 7 successive days were determined to be 5.54 h on the 1st day and 6.91 h on the 7th day, displaying the increase in half-life value with the repetitive dosing. While, the predicted value determined using the experimental value on the 1st day agreed with the experimental value on the 7th day. Furthermore, the amounts of carteolol excreted in the urine were not significantly different between the 1st and 7th days. The 7-day repetitive administration with carteolol brought about the steady state of plasma levels. It was concluded from these results that carteolol has little ability to accumulate in man.", "contents": "Metabolic fate of carteolol hydrochloride, (OPC-1085) VIII, a new beta-adrenergic blocking agent. Pharmacokinetic studies of carteolol in man. The pharmacokinetics of 5-(3-tert.-butylamino-2-hydroxy)-propoxy-3,4-dihydrocarbostyril hydrochloride (carteolol hydrochloride, OPC-1085) have been investigated in man following single or repetitive oral administration. The plasma half-lives. The plasma half-lives of carteolol at single doses of 10, 15 and 30 mg were 5.4, 5.5 and 5.0 h, respectively. The amounts of carteolol excreted into urine within 24 h at the same dose levels accounted for 64, 70 and 76% of the respective doses. The half-lives obtained by the Sigmaminus method were 5.6, 5.6 and 5.4 h, respectively, being essentially consistent with the aforementioned plasma half-lives of carteolol after administration at 15 mg daily for 7 successive days were determined to be 5.54 h on the 1st day and 6.91 h on the 7th day, displaying the increase in half-life value with the repetitive dosing. While, the predicted value determined using the experimental value on the 1st day agreed with the experimental value on the 7th day. Furthermore, the amounts of carteolol excreted in the urine were not significantly different between the 1st and 7th days. The 7-day repetitive administration with carteolol brought about the steady state of plasma levels. It was concluded from these results that carteolol has little ability to accumulate in man."}
{"id": "PMID:23801", "title": "Bioavailability from various galenic formulations of flunitrazepam.", "content": "The absolute and relative bioavailability of flunitrazepam (Rohypnol) tablet, oral solution and suppository formulations was determined in a cross-over study on 6 healthy volunteers. The tablet and the oral solution were shown to be bioequivalent, absorption being at least 80%. For flunitrazepam suppositories the bioavailability was found to be about 50%. The plasma concentrations are described on the basis of a three-compartment model, the adjustment of the curves from the same subject being made simultaneously. The central compartment and the second compartment are about equal in size and rapid exchange takes place between them. The third compartment is about four times as large as the central one. The slow reflux of the compound from the third to the first compartment is the rate determining factor for the overall elimination in the beta-phase.", "contents": "Bioavailability from various galenic formulations of flunitrazepam. The absolute and relative bioavailability of flunitrazepam (Rohypnol) tablet, oral solution and suppository formulations was determined in a cross-over study on 6 healthy volunteers. The tablet and the oral solution were shown to be bioequivalent, absorption being at least 80%. For flunitrazepam suppositories the bioavailability was found to be about 50%. The plasma concentrations are described on the basis of a three-compartment model, the adjustment of the curves from the same subject being made simultaneously. The central compartment and the second compartment are about equal in size and rapid exchange takes place between them. The third compartment is about four times as large as the central one. The slow reflux of the compound from the third to the first compartment is the rate determining factor for the overall elimination in the beta-phase."}
{"id": "PMID:23802", "title": "[Importance of ventilation in metabolic acidosis].", "content": "The study included ten patients with severe metabolic acidosis (pH under 7.0) and clinical signs of shock. In four of them assisted ventilation was indicated as an urgency. In the other six patients assisted ventilation was used since the beginning, simultaneously with reposition of blood volume and administration of sodium bicarbonate. There were much better results with the latter management, with faster correction of the acidosis, without any complications and good survivorship.", "contents": "[Importance of ventilation in metabolic acidosis]. The study included ten patients with severe metabolic acidosis (pH under 7.0) and clinical signs of shock. In four of them assisted ventilation was indicated as an urgency. In the other six patients assisted ventilation was used since the beginning, simultaneously with reposition of blood volume and administration of sodium bicarbonate. There were much better results with the latter management, with faster correction of the acidosis, without any complications and good survivorship."}
{"id": "PMID:23821", "title": "Severe hypercapnia associated with a non-respiratory alkalosis.", "content": "A case of hypoventilation in response to a non-respiratory alkalosis is presented. It is postulated that the degree of hypoventilation encountered was a normal response and that a fall in intracellular hydrogen ion concentration was responsible for the hypoventilation. This explains why the alkalosis associated with potassium deficiency is not associated with hypoventilation since the intracellular hydrogen ion concentration then remains constant. The renal response in this condition is responsible for maintaining the alkalosis and seems to be aimed at sodium conservation and hence plasma volume control rather than defence of acid-base balance.", "contents": "Severe hypercapnia associated with a non-respiratory alkalosis. A case of hypoventilation in response to a non-respiratory alkalosis is presented. It is postulated that the degree of hypoventilation encountered was a normal response and that a fall in intracellular hydrogen ion concentration was responsible for the hypoventilation. This explains why the alkalosis associated with potassium deficiency is not associated with hypoventilation since the intracellular hydrogen ion concentration then remains constant. The renal response in this condition is responsible for maintaining the alkalosis and seems to be aimed at sodium conservation and hence plasma volume control rather than defence of acid-base balance."}
{"id": "PMID:23822", "title": "Personnel radiation dosimetry in drug photosensitivity: field study of patients on phenothiazine therapy.", "content": "A lapel badge dosimeter sensitive to short wave UVR has been used in a preliminary trial to survey photosensitivity in psychiatric patients on phenothiazine therapy. The badge was found easy to use and the results suggest that chlorpromazine is more photosensitizing than other phenothiazines.", "contents": "Personnel radiation dosimetry in drug photosensitivity: field study of patients on phenothiazine therapy. A lapel badge dosimeter sensitive to short wave UVR has been used in a preliminary trial to survey photosensitivity in psychiatric patients on phenothiazine therapy. The badge was found easy to use and the results suggest that chlorpromazine is more photosensitizing than other phenothiazines."}
{"id": "PMID:23823", "title": "Intraerythrocyte pH, pCO2 and the hexose monophosphate shunt.", "content": "We have documented a rise in pCO2 when erythrocytes are haemolysed by freeze-thaw using solid CO2 and methanol. This is partially corrected by preventing leakage of CO2 into the system. The remaining increment is partially explained by stimulation of the hexose monophosphate shunt when erythrocytes are haemolysed by this technique.", "contents": "Intraerythrocyte pH, pCO2 and the hexose monophosphate shunt. We have documented a rise in pCO2 when erythrocytes are haemolysed by freeze-thaw using solid CO2 and methanol. This is partially corrected by preventing leakage of CO2 into the system. The remaining increment is partially explained by stimulation of the hexose monophosphate shunt when erythrocytes are haemolysed by this technique."}
{"id": "PMID:23825", "title": "Interaction of ribonuclease A with aqueous 2-methyl-2,4-pentanediol at pH 5.8.", "content": "The interactions between ribonuclease A and solvent components in aqueous 2-methyl-2,4-pentanediol (MPD) have been investigated by differential refractometry and light scattering at pH 5.8, i.e., conditions similar to those used to crystallize the protein from this solvent system. Application of multicomponent thermodynamic theory shows that, at all solvent compositions up to 50% (v/v) MPD, the protein is preferentially hydrated; i.e., addition of ribonuclease to the mixed solvent leads to an increase in the chemical potential of MPD. This unfavorable thermodynamic interaction leads to phase separation, probably caused by local salting out of the MPD by the charges on the surface of the protein molecule. A parallel examination by circular dichroism (CD) has shown that the CD spectrum of ribonuclease in 50% MPD is indistinguishable from that in dilute buffer.", "contents": "Interaction of ribonuclease A with aqueous 2-methyl-2,4-pentanediol at pH 5.8. The interactions between ribonuclease A and solvent components in aqueous 2-methyl-2,4-pentanediol (MPD) have been investigated by differential refractometry and light scattering at pH 5.8, i.e., conditions similar to those used to crystallize the protein from this solvent system. Application of multicomponent thermodynamic theory shows that, at all solvent compositions up to 50% (v/v) MPD, the protein is preferentially hydrated; i.e., addition of ribonuclease to the mixed solvent leads to an increase in the chemical potential of MPD. This unfavorable thermodynamic interaction leads to phase separation, probably caused by local salting out of the MPD by the charges on the surface of the protein molecule. A parallel examination by circular dichroism (CD) has shown that the CD spectrum of ribonuclease in 50% MPD is indistinguishable from that in dilute buffer."}
{"id": "PMID:23826", "title": "31P nuclear magnetic resonance spectra of the thiophosphate analogues of adenine nucleotides; effects of pH and Mg2+ binding.", "content": "The 31P nuclear magnetic resonance (NMR) spectra of the adenine nucleotide thio analogues, AMPS, ADPalphaS, ADPbetaS, ATPalphaS, ATPbetaS, and ATPgammaS, have been studied. Of primary interest were the increased sensitivity of chemical shifts to protonation and to magnesium binding of these analogues compared with the corresponding effects on AMP, ADP, and ATP. The usefulness of the characteristic NMR parameters of the thio analogues as probes in enzymatic reactions is discussed. The A2 diastereoisomers of ADPalphaS and ATPalphaS and the A and B isomers of ATPbetaS were enzymatically synthesized and the diasterioisomers of ADPalphaS and ATPbetaS were distinguished by their 31P NMR parameters. The stereospecificity of the enzymatic reactions involving the thio analogues of nucleotides can therefore be determined by 31P NMR. The difficulty involved in assigning phosphate ligands of Mg in MgADP and MgATP and their analogues on the basis of the magnitude of chemical shift changes (deltadelta) induced by Mg binding upon each 31P is discussed in the context of the anomalies in deltadelta of each 31P observed upon protonation of the terminal phosphate group. It is concluded that chemical shift data cannot yield unequivocal information concerning the absolute structure of metal complexes of nucleotides but can be used to monitor changes in metal chelation, for example, upon binding to enzyme.", "contents": "31P nuclear magnetic resonance spectra of the thiophosphate analogues of adenine nucleotides; effects of pH and Mg2+ binding. The 31P nuclear magnetic resonance (NMR) spectra of the adenine nucleotide thio analogues, AMPS, ADPalphaS, ADPbetaS, ATPalphaS, ATPbetaS, and ATPgammaS, have been studied. Of primary interest were the increased sensitivity of chemical shifts to protonation and to magnesium binding of these analogues compared with the corresponding effects on AMP, ADP, and ATP. The usefulness of the characteristic NMR parameters of the thio analogues as probes in enzymatic reactions is discussed. The A2 diastereoisomers of ADPalphaS and ATPalphaS and the A and B isomers of ATPbetaS were enzymatically synthesized and the diasterioisomers of ADPalphaS and ATPbetaS were distinguished by their 31P NMR parameters. The stereospecificity of the enzymatic reactions involving the thio analogues of nucleotides can therefore be determined by 31P NMR. The difficulty involved in assigning phosphate ligands of Mg in MgADP and MgATP and their analogues on the basis of the magnitude of chemical shift changes (deltadelta) induced by Mg binding upon each 31P is discussed in the context of the anomalies in deltadelta of each 31P observed upon protonation of the terminal phosphate group. It is concluded that chemical shift data cannot yield unequivocal information concerning the absolute structure of metal complexes of nucleotides but can be used to monitor changes in metal chelation, for example, upon binding to enzyme."}
{"id": "PMID:23827", "title": "Studies of the control of luminescence in Beneckea harveyi: properties of the NADH and NADPH:FMN oxidoreductases.", "content": "Highly purified NADH and NADPH:FMN oxidoreductases from Beneckea harveyi have been characterized with regard to kinetic parameters, association with luciferase, activity with artificial electron acceptors, and the effects of inhibitors. The NADH:FMN oxidoreductase exhibits single displacement kinetics while the NADPH:FMN oxidoreductase exhibits double displacement or ping-pong kinetics. This is consistent with the formation of a reduced enzyme as an intermediate in the reaction of catalyzed by the NADPH:FMN oxidoreductase. Coupling of either of the oxidoreductases to the luciferase reaction decreases the apparent Kms for NADH, NADPH, and FMN, supporting the suggestion of a complex between the oxidoreductases and luciferase. The soluble oxidoreductases are more efficient in producing light with luciferase than is a NADH dehydrogenase preparation obtained from the membranes of these bacteria. The soluble enzymes use either FMN or FAD as substrates for the oxidation of reduced pyridine nucleotides while the membrane NADH dehydrogenase is much more active with artificial electron acceptors such as ferricyanide and methylene blue. FMN and FAD are very poor acceptors. The evidence indicates that neither of the soluble oxidoreductases is derived from the membranes. Both enzymes are constitutive and do not depend on the synthesis of luciferase.", "contents": "Studies of the control of luminescence in Beneckea harveyi: properties of the NADH and NADPH:FMN oxidoreductases. Highly purified NADH and NADPH:FMN oxidoreductases from Beneckea harveyi have been characterized with regard to kinetic parameters, association with luciferase, activity with artificial electron acceptors, and the effects of inhibitors. The NADH:FMN oxidoreductase exhibits single displacement kinetics while the NADPH:FMN oxidoreductase exhibits double displacement or ping-pong kinetics. This is consistent with the formation of a reduced enzyme as an intermediate in the reaction of catalyzed by the NADPH:FMN oxidoreductase. Coupling of either of the oxidoreductases to the luciferase reaction decreases the apparent Kms for NADH, NADPH, and FMN, supporting the suggestion of a complex between the oxidoreductases and luciferase. The soluble oxidoreductases are more efficient in producing light with luciferase than is a NADH dehydrogenase preparation obtained from the membranes of these bacteria. The soluble enzymes use either FMN or FAD as substrates for the oxidation of reduced pyridine nucleotides while the membrane NADH dehydrogenase is much more active with artificial electron acceptors such as ferricyanide and methylene blue. FMN and FAD are very poor acceptors. The evidence indicates that neither of the soluble oxidoreductases is derived from the membranes. Both enzymes are constitutive and do not depend on the synthesis of luciferase."}
{"id": "PMID:23831", "title": "Purification and properties of deoxyribonuclease from human urine.", "content": "The DNAase in human urine was purified about 30-fold with a recovery of 28%. This involved DEAE-cellulose and phosphocellulose chromatography steps and gel filtration on Sephadex G-75. The enzyme required divalent cations such as Co2+, Mg2+, Mn2+ and Zn2+ for activity, but Ca2+, Cu2+ and Fe2+ were ineffective. EDTA and G-actin inhibited the reaction. The maximum activity was observed at pH 5.5 in acetate buffer plus Co2+ or Mg2+ and Ca2+. It had a molecular weight of approximately 38 000, estimated by gel filtration on Sephadex G-75 and isoelectric point of around pH 3.9. The enzyme is an endonuclease which hydrolyzes native, double-stranded DNA about 3 to 4 times faster than thermally denatured DNA to produce 5'-phosphoryl- and 3'-hydroxyl-terminated oligonucleotides. The final preparation was free of non-specific acid and alkaline phosphatases, phosphodiesterase and ribonuclease activities.", "contents": "Purification and properties of deoxyribonuclease from human urine. The DNAase in human urine was purified about 30-fold with a recovery of 28%. This involved DEAE-cellulose and phosphocellulose chromatography steps and gel filtration on Sephadex G-75. The enzyme required divalent cations such as Co2+, Mg2+, Mn2+ and Zn2+ for activity, but Ca2+, Cu2+ and Fe2+ were ineffective. EDTA and G-actin inhibited the reaction. The maximum activity was observed at pH 5.5 in acetate buffer plus Co2+ or Mg2+ and Ca2+. It had a molecular weight of approximately 38 000, estimated by gel filtration on Sephadex G-75 and isoelectric point of around pH 3.9. The enzyme is an endonuclease which hydrolyzes native, double-stranded DNA about 3 to 4 times faster than thermally denatured DNA to produce 5'-phosphoryl- and 3'-hydroxyl-terminated oligonucleotides. The final preparation was free of non-specific acid and alkaline phosphatases, phosphodiesterase and ribonuclease activities."}
{"id": "PMID:23832", "title": "Study on plant RNAases. Isolation and properties of several activities from Vicia faba root cells.", "content": "Vicia faba root cells contain several nucleolytic activities: phosphomonoesterase and phosphodiesterase (which however were not studied in details), one nuclease and four ribonucleases. These results were obtained by separating the extracted proteins into anionic and cationic species by chromatography on CM-cellulose at pH 5.5 and analysing each kind of proteins. Anionic species were subjected to chromatography on DEAE-cellulose which lead to isolation of one nuclease (A1) and two RNAases (A2, A3), the properties of which were studied. It was shown that the RNAases pH optima are near 6; A2 is more thermolabile than A3; both are endonucleases unable to attack double-stranded structure; studies with homopolymers, i.e. poly(A), poly(I), poly(C), poly(U), showed that their base specificities were analogous to that of already known plant RNAases. The cationic proteins, analysed with CM-cellulose, contain two RNAases (C1, C2). The pH optima were near 6 and 7, respectively; C1 is much more thermolabile than C2; both were endonucleases inactive on double-stranded structures. C1 and C2 hydrolysed poly(C) and poly(U) but not poly(A) and poly(U).", "contents": "Study on plant RNAases. Isolation and properties of several activities from Vicia faba root cells. Vicia faba root cells contain several nucleolytic activities: phosphomonoesterase and phosphodiesterase (which however were not studied in details), one nuclease and four ribonucleases. These results were obtained by separating the extracted proteins into anionic and cationic species by chromatography on CM-cellulose at pH 5.5 and analysing each kind of proteins. Anionic species were subjected to chromatography on DEAE-cellulose which lead to isolation of one nuclease (A1) and two RNAases (A2, A3), the properties of which were studied. It was shown that the RNAases pH optima are near 6; A2 is more thermolabile than A3; both are endonucleases unable to attack double-stranded structure; studies with homopolymers, i.e. poly(A), poly(I), poly(C), poly(U), showed that their base specificities were analogous to that of already known plant RNAases. The cationic proteins, analysed with CM-cellulose, contain two RNAases (C1, C2). The pH optima were near 6 and 7, respectively; C1 is much more thermolabile than C2; both were endonucleases inactive on double-stranded structures. C1 and C2 hydrolysed poly(C) and poly(U) but not poly(A) and poly(U)."}
{"id": "PMID:23834", "title": "Studies of the catalytic properties of an endonuclease isolated from Tetrahymena pyriformis.", "content": "An acid endonuclease hydrolyzing both DNA and RNA was purified from Tetrahymena pyriformis, strain E. The enzyme is distributed in all major subcellular compartments and is excreted into the growth medium towards the middle of the logarithmic phase. It hydrolyzes DNA to penta or hexanucleotides, on the average, bearing the monoesterified phosphate at the 3'-position. Particularly in early phases of the reaction it shows a very pronounced specificity for bases with a keto group at position 4 of the pyrimidine ring, such as guanine and thymine.", "contents": "Studies of the catalytic properties of an endonuclease isolated from Tetrahymena pyriformis. An acid endonuclease hydrolyzing both DNA and RNA was purified from Tetrahymena pyriformis, strain E. The enzyme is distributed in all major subcellular compartments and is excreted into the growth medium towards the middle of the logarithmic phase. It hydrolyzes DNA to penta or hexanucleotides, on the average, bearing the monoesterified phosphate at the 3'-position. Particularly in early phases of the reaction it shows a very pronounced specificity for bases with a keto group at position 4 of the pyrimidine ring, such as guanine and thymine."}
{"id": "PMID:23835", "title": "Purification and properties of a cyclic AMP-independent protein kinase from calf thymus nuclei.", "content": "A phosphoprotein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) from calf thymus nuclei was purified by DEAE-cellulose chromatography, hydroxyapatite, and Sepharose 6B gel filtration. The enzyme is a cyclic AMP-independent protein kinase by the following criteria: (a) the protein kinase did not bind cyclic AMP; (b) no inhibition of activity was obtained with the heat-stable protein kinase inhibitor from rabbit skeletal muscle; (c) the regulatory subunit of cyclic AMP-dependent protein kinase had no effect on activity; and (d) no inhibition was obtained with antibody to cyclic AMP-dependent protein kinase. The nuclear cyclic AMP-independent protein kinase readily phosphorylated protamine on serine and to a lesser extent on threonine. Homologous nucleoplasmic RNA polymerase (EC 2.7.7.6) is a better substrate than arginine-rich histone, phosvitin or casein. Physical characteristics of the enzyme are described.", "contents": "Purification and properties of a cyclic AMP-independent protein kinase from calf thymus nuclei. A phosphoprotein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) from calf thymus nuclei was purified by DEAE-cellulose chromatography, hydroxyapatite, and Sepharose 6B gel filtration. The enzyme is a cyclic AMP-independent protein kinase by the following criteria: (a) the protein kinase did not bind cyclic AMP; (b) no inhibition of activity was obtained with the heat-stable protein kinase inhibitor from rabbit skeletal muscle; (c) the regulatory subunit of cyclic AMP-dependent protein kinase had no effect on activity; and (d) no inhibition was obtained with antibody to cyclic AMP-dependent protein kinase. The nuclear cyclic AMP-independent protein kinase readily phosphorylated protamine on serine and to a lesser extent on threonine. Homologous nucleoplasmic RNA polymerase (EC 2.7.7.6) is a better substrate than arginine-rich histone, phosvitin or casein. Physical characteristics of the enzyme are described."}
{"id": "PMID:23836", "title": "Methylamine dehydrogenase of Pseudomonas sp. J. Purification and properties.", "content": "Methylamine dehydrogenase was purified in a homogeneous form from methylamine-grown Pseudomonas sp. J. The specific activity of the purified enzyme was 5.19 at 19 degrees C. The molecular weight was estimated to be 105 000, and the enzyme was composed of two kinds of subunit with molecular weights of 40 000 and 13 000, respectively. The enzyme contained little phosphorus, iron and copper. The enzyme had absorption maxima at 278, 330, 430 and 460 nm (shoulder). On addition of methylamine, the peaks at 430 and 460 nm decreased, while that at 330 nm increased. Primary amines served as substrates, but secondary and tertiary amines did not. Phenazine methosulfate was the most effective electron acceptor and oxygen was ineffective. The enzyme was inhibited by carbonyl reagents, cuprizone and HgCl2 but not by other chelators or sulfhydryl reagents. Some of other physical and biochemical properties of the enzyme were studied. These results show that the enzyme purified from Pseudomonas sp. J is essentially similar to the enzyme obtained from Pseudomonas AM1, although it differs slightly in some properties.", "contents": "Methylamine dehydrogenase of Pseudomonas sp. J. Purification and properties. Methylamine dehydrogenase was purified in a homogeneous form from methylamine-grown Pseudomonas sp. J. The specific activity of the purified enzyme was 5.19 at 19 degrees C. The molecular weight was estimated to be 105 000, and the enzyme was composed of two kinds of subunit with molecular weights of 40 000 and 13 000, respectively. The enzyme contained little phosphorus, iron and copper. The enzyme had absorption maxima at 278, 330, 430 and 460 nm (shoulder). On addition of methylamine, the peaks at 430 and 460 nm decreased, while that at 330 nm increased. Primary amines served as substrates, but secondary and tertiary amines did not. Phenazine methosulfate was the most effective electron acceptor and oxygen was ineffective. The enzyme was inhibited by carbonyl reagents, cuprizone and HgCl2 but not by other chelators or sulfhydryl reagents. Some of other physical and biochemical properties of the enzyme were studied. These results show that the enzyme purified from Pseudomonas sp. J is essentially similar to the enzyme obtained from Pseudomonas AM1, although it differs slightly in some properties."}
{"id": "PMID:23837", "title": "Methylamine dehydrogenase of Pseudomonase sp. J Isolation and properties of the subunits.", "content": "Two kinds of subunits, light subunit (Mr =1300) and heavy subunit (Mr=40 000), were isolated from a methylamine dehydrogenase (Mr=105 000) of Pseudomonas sp. J. The isolation of the subunits was carried out by gel chromatography after the enzyme had been treated with 3M guanidine-HCl. Coexistence of both of the subunit exhibited an absorption maximum only at 278 nm but in addition to the peak at 278 nm. The results indicate that the prosthetic group, assumed to be a derivative of pyridoxal, was bound to the light subunit. The spectral changes of the light subunit were observed by addition of methylamine. Various physical and biochemical parameters of the subunits are reported.", "contents": "Methylamine dehydrogenase of Pseudomonase sp. J Isolation and properties of the subunits. Two kinds of subunits, light subunit (Mr =1300) and heavy subunit (Mr=40 000), were isolated from a methylamine dehydrogenase (Mr=105 000) of Pseudomonas sp. J. The isolation of the subunits was carried out by gel chromatography after the enzyme had been treated with 3M guanidine-HCl. Coexistence of both of the subunit exhibited an absorption maximum only at 278 nm but in addition to the peak at 278 nm. The results indicate that the prosthetic group, assumed to be a derivative of pyridoxal, was bound to the light subunit. The spectral changes of the light subunit were observed by addition of methylamine. Various physical and biochemical parameters of the subunits are reported."}
{"id": "PMID:23838", "title": "Methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase from porcine liver. Interaction between the dehydrogenase and cyclohydrolase activities of the multifunctional enzyme.", "content": "Methylenetetrahydrofolate dehydrogenase (5,10-methylenetetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.5) one of the activities of a trifunctional folate-dependent enzyme from porcine liver, uses an ordered kinetic mechannism as determined from initial velocity, product inhibition and dead-end inhibition studies. The final product released from the dehydrogenase is methenyltetrahydrofolate. However, from the time course of appearance of products it is observed that the methenyltetrahydrofolate, rather than equilibrating with the solution, is converted preferentially to formyltetrahydrofolate by the cyclohydrolase, (5,10-methenyletrahydrofolate 5-hydrolase (decyclizing), EC 3.5.4.9) demonstrating a functional interaction between these two enzymic activites.", "contents": "Methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase from porcine liver. Interaction between the dehydrogenase and cyclohydrolase activities of the multifunctional enzyme. Methylenetetrahydrofolate dehydrogenase (5,10-methylenetetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.5) one of the activities of a trifunctional folate-dependent enzyme from porcine liver, uses an ordered kinetic mechannism as determined from initial velocity, product inhibition and dead-end inhibition studies. The final product released from the dehydrogenase is methenyltetrahydrofolate. However, from the time course of appearance of products it is observed that the methenyltetrahydrofolate, rather than equilibrating with the solution, is converted preferentially to formyltetrahydrofolate by the cyclohydrolase, (5,10-methenyletrahydrofolate 5-hydrolase (decyclizing), EC 3.5.4.9) demonstrating a functional interaction between these two enzymic activites."}
{"id": "PMID:23840", "title": "Multiple forms of gamma-glutamyltransferase in normal human liver, bile and serum.", "content": "A study of the multiple forms of gamma-glutamyltransferase ((gamma-glutamyl)-peptide:amino acid gamma-glutamyltransferase, EC 2.3.2.2) in normal human liver, bile and serum are reported. An amphiphilic form of the enzyme was demonstrated in all three samples. When solubilized with detergent, estimated values for Stoke's radius of 48 A and sedimentation coefficient of 5 S were obtained for this form. A hydrophilic form was also present in serum and bile, which showed identical properties to the enzyme form obtained after papain-treatment of the three samples. The Stoke's radius was found to be 37 A, and the sedimentation coefficient 5 S. It was concluded that the heterogeneity of enzyme activity found both on gel filtration and on electrophoresis was due to aggregates of the amphiphilic form with lipids and other proteins, and could not be ascribed to the presence of isoenzymes.", "contents": "Multiple forms of gamma-glutamyltransferase in normal human liver, bile and serum. A study of the multiple forms of gamma-glutamyltransferase ((gamma-glutamyl)-peptide:amino acid gamma-glutamyltransferase, EC 2.3.2.2) in normal human liver, bile and serum are reported. An amphiphilic form of the enzyme was demonstrated in all three samples. When solubilized with detergent, estimated values for Stoke's radius of 48 A and sedimentation coefficient of 5 S were obtained for this form. A hydrophilic form was also present in serum and bile, which showed identical properties to the enzyme form obtained after papain-treatment of the three samples. The Stoke's radius was found to be 37 A, and the sedimentation coefficient 5 S. It was concluded that the heterogeneity of enzyme activity found both on gel filtration and on electrophoresis was due to aggregates of the amphiphilic form with lipids and other proteins, and could not be ascribed to the presence of isoenzymes."}
{"id": "PMID:23841", "title": "Biosynthesis of glycogen in Neurospora crassa. Purification and properties of the UDPglucose:glycogen 4-alpha-glucosyltransferase.", "content": "The Neurospora crassa glycogen synthase (UDPglucose:glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11) was purified to electrophoretic homogeneity by a procedure involving ultracentrifugation, DEAE-cellulose column chromatography, (NH4)2SO4 fractionation and 3-aminopropyl-Sepharose column chromatography. The final purified enzyme preparation was almost entirely dependent on glucose-6-P and had a specific activity of 6.9 units per mg of protein. The subunit molecular weight of the glycogen synthase was determined by electrophoresis in sodium dodecyl sulfate-polyacrylamide gel to be 88 000--90 000. The native enzyme was shown to have a molecular weight of 270 000 as determined by sucrose density gradient centrifugation. Thus, the glucose-6-P-dependent form of the N. crassa glycogen synthase can exist as trimer of the subunit. Limited proteolysis with trypsin or chymotrypsin converted the glucose-6-P-dependent form of the enzyme into an apparent glucose-6-P-independent form. The enzyme was shown to catalyze transfer of glucose from UDPglucose to glycogen as well as to its phosphorylase limit dextrin, but not to its beta-amylase limit dextrin. Moreover, glucose, maltose and maltotriose were not active as acceptors.", "contents": "Biosynthesis of glycogen in Neurospora crassa. Purification and properties of the UDPglucose:glycogen 4-alpha-glucosyltransferase. The Neurospora crassa glycogen synthase (UDPglucose:glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11) was purified to electrophoretic homogeneity by a procedure involving ultracentrifugation, DEAE-cellulose column chromatography, (NH4)2SO4 fractionation and 3-aminopropyl-Sepharose column chromatography. The final purified enzyme preparation was almost entirely dependent on glucose-6-P and had a specific activity of 6.9 units per mg of protein. The subunit molecular weight of the glycogen synthase was determined by electrophoresis in sodium dodecyl sulfate-polyacrylamide gel to be 88 000--90 000. The native enzyme was shown to have a molecular weight of 270 000 as determined by sucrose density gradient centrifugation. Thus, the glucose-6-P-dependent form of the N. crassa glycogen synthase can exist as trimer of the subunit. Limited proteolysis with trypsin or chymotrypsin converted the glucose-6-P-dependent form of the enzyme into an apparent glucose-6-P-independent form. The enzyme was shown to catalyze transfer of glucose from UDPglucose to glycogen as well as to its phosphorylase limit dextrin, but not to its beta-amylase limit dextrin. Moreover, glucose, maltose and maltotriose were not active as acceptors."}
{"id": "PMID:23842", "title": "Purification and properties of 4-aminobutyrate 2-ketoglutarate aminotransferase from pig liver.", "content": "4-Aminobutyrate-transaminase (4-aminobutyrate: 2-oxoglutarate amino-transferase, EC 2.6.1.19) from pig liver has been purified to electrophoretic homogeneity. It has a molecular weight of about 110 000 and is composed of two subunits of the same molecular weight but of different charges. Two forms of pig liver 4-aminobutyrate-transaminase were isolated by DEAE-cellulose chromatography and designated as 4-aminobutyrate-transaminase I and 4-aminobutyrate-transaminase II, corresponding to a cationic and anionic form. Some physical and kinetic properties of liver enzyme were compared to those of brain enzyme and no significant difference were found, except for their sedimentation coefficients and the charges of their subunits. The role of 4-aminobutyrate-transaminase in liver remains a matter of speculation, but could be related to a metabolic function.", "contents": "Purification and properties of 4-aminobutyrate 2-ketoglutarate aminotransferase from pig liver. 4-Aminobutyrate-transaminase (4-aminobutyrate: 2-oxoglutarate amino-transferase, EC 2.6.1.19) from pig liver has been purified to electrophoretic homogeneity. It has a molecular weight of about 110 000 and is composed of two subunits of the same molecular weight but of different charges. Two forms of pig liver 4-aminobutyrate-transaminase were isolated by DEAE-cellulose chromatography and designated as 4-aminobutyrate-transaminase I and 4-aminobutyrate-transaminase II, corresponding to a cationic and anionic form. Some physical and kinetic properties of liver enzyme were compared to those of brain enzyme and no significant difference were found, except for their sedimentation coefficients and the charges of their subunits. The role of 4-aminobutyrate-transaminase in liver remains a matter of speculation, but could be related to a metabolic function."}
{"id": "PMID:23843", "title": "Purification and properties of polynucleotide kinase of calf thymus.", "content": "Polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) has been purified approx. 1500-fold from calf thymus. This enzyme phosphorylates 5'-hydroxyl termini in DNA using ATP as phosphate donor. RNA is phosphorylated at a much lower rate than DNA. The reaction requires the presence of a divalent cation, preferably Mg2+ or Mn2+ and is sensitive to sulfhydryl antagonists. The optimum pH for enzyme activity is 5.5. Enzyme activity is inhibited by low concentrations of inorganic sulfate and by some sulfate polymers. The kinase-catalyzed incorporation of the terminal phosphate of ATP into polynucleotides is inhibited by other nucleoside and deoxynucleoside triphosphates. The enzyme molecule has a molecular weight of about 70 000 and a Stokes radius of 4.3 nm. It has a frictional ratio of 1.44 indicating an asymmetrical structure. Calf thymus tissue should provide a useful alternative source for preparation of mammalian polynucleotide kinase.", "contents": "Purification and properties of polynucleotide kinase of calf thymus. Polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) has been purified approx. 1500-fold from calf thymus. This enzyme phosphorylates 5'-hydroxyl termini in DNA using ATP as phosphate donor. RNA is phosphorylated at a much lower rate than DNA. The reaction requires the presence of a divalent cation, preferably Mg2+ or Mn2+ and is sensitive to sulfhydryl antagonists. The optimum pH for enzyme activity is 5.5. Enzyme activity is inhibited by low concentrations of inorganic sulfate and by some sulfate polymers. The kinase-catalyzed incorporation of the terminal phosphate of ATP into polynucleotides is inhibited by other nucleoside and deoxynucleoside triphosphates. The enzyme molecule has a molecular weight of about 70 000 and a Stokes radius of 4.3 nm. It has a frictional ratio of 1.44 indicating an asymmetrical structure. Calf thymus tissue should provide a useful alternative source for preparation of mammalian polynucleotide kinase."}
{"id": "PMID:23844", "title": "Purification and characterization of two isozymes of 3-phosphoglycerate kinase from the mouse.", "content": "Two isozymes of 3-phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), designated PGK-A and PGK-B, were purified from separate extracts of muscle and testicular tissue of DBA/2J mice, respectively. A similar procedure was used to purify the corresponding isozymes from C57BL/6J mice in order to make inter-strain comparisons. The purification involved the use of affinity chromatography with an 8-(6-aminohexyl)amino-ATP-Sepharose column and DEAE-Sephadex chromatography. Lactate dehydrogenase isozyme LDH-X was also co-purified from extract of mouse testes by this two-step procedure. The same isozyme isolated from either mouse strain was found to be identical in physical and biochemical properties. Both isozymes are monomeric as determined by gel filtration chromatography and by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Furthermore, the isozymes have similar molecular weights, of 47 000 +/- 2000 and exhibit similar Km values for both coenzymes and substrate, as well as temperature dependence of enzyme activity. However, it was observed that the B isozyme is more labile than the A isozyme by denaturation at high temperature, urea and acidic pH.", "contents": "Purification and characterization of two isozymes of 3-phosphoglycerate kinase from the mouse. Two isozymes of 3-phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), designated PGK-A and PGK-B, were purified from separate extracts of muscle and testicular tissue of DBA/2J mice, respectively. A similar procedure was used to purify the corresponding isozymes from C57BL/6J mice in order to make inter-strain comparisons. The purification involved the use of affinity chromatography with an 8-(6-aminohexyl)amino-ATP-Sepharose column and DEAE-Sephadex chromatography. Lactate dehydrogenase isozyme LDH-X was also co-purified from extract of mouse testes by this two-step procedure. The same isozyme isolated from either mouse strain was found to be identical in physical and biochemical properties. Both isozymes are monomeric as determined by gel filtration chromatography and by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Furthermore, the isozymes have similar molecular weights, of 47 000 +/- 2000 and exhibit similar Km values for both coenzymes and substrate, as well as temperature dependence of enzyme activity. However, it was observed that the B isozyme is more labile than the A isozyme by denaturation at high temperature, urea and acidic pH."}
{"id": "PMID:23846", "title": "Solubilization and partial characterization of a phosphoprotein phosphatase from human myelin.", "content": "The phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) solubilized from human central nervous system myelin has been shown to possess a comparatively high degree of specificity towards myelin basic protein, a constituent of the membrane and most likely its natural substrate, rather than the mixed histones. The enzyme has a pH optimum of 7.5. Hydrolysis of both the substrates is stimulated by dithiothreitol and is almost completely dependent upon the presence of divalent metal ions. The maximum rate of dephosphorylation of basic protein is attained in the presence of 125 micrometer Mn2+ whereas a much higher concentration of Mg2+ (50--100 mM) is required for the optimal dephosphorylation of histones. The dephosphorylation of basic protein was also stimulated by Triton X-100 (0.15%, v/v) and was shown to result from a 3-fold increase in the V of the reaction catalyzed by the phosphatase. The apparent Km values for basic protein and histones were unaffected by the presence of Triton X-100 and were found to be approx. 1 and approx. 160 micrometer, respectively. Under optimal conditions of assay, the phosphatase cleaved approx. 32 and approx. 0.7 nmol of orthophosphate.min-1.mg-1 of protein from basic protein and histones, respectively.", "contents": "Solubilization and partial characterization of a phosphoprotein phosphatase from human myelin. The phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) solubilized from human central nervous system myelin has been shown to possess a comparatively high degree of specificity towards myelin basic protein, a constituent of the membrane and most likely its natural substrate, rather than the mixed histones. The enzyme has a pH optimum of 7.5. Hydrolysis of both the substrates is stimulated by dithiothreitol and is almost completely dependent upon the presence of divalent metal ions. The maximum rate of dephosphorylation of basic protein is attained in the presence of 125 micrometer Mn2+ whereas a much higher concentration of Mg2+ (50--100 mM) is required for the optimal dephosphorylation of histones. The dephosphorylation of basic protein was also stimulated by Triton X-100 (0.15%, v/v) and was shown to result from a 3-fold increase in the V of the reaction catalyzed by the phosphatase. The apparent Km values for basic protein and histones were unaffected by the presence of Triton X-100 and were found to be approx. 1 and approx. 160 micrometer, respectively. Under optimal conditions of assay, the phosphatase cleaved approx. 32 and approx. 0.7 nmol of orthophosphate.min-1.mg-1 of protein from basic protein and histones, respectively."}
{"id": "PMID:23847", "title": "Acid glycohydrolase in Chinese hamster with spontaneous diabetes. I. Depressed levels of renal alpha-galactosidase and beta-galactosidase.", "content": "The activites of alpha-and Beta-galactosidases (alpha-D-galactoside galactohydrolase, EC 3.2.1.22; beta-D-galactoside galactohydrolase, EC 3.2.1.23) were significantly lower in the kidneys of diabetic XA line than those in the nondiabetic M line Chinese hamsters. The depression of these enzymes was found only in the kidney but not in liver, spleen, hind leg muscle, cheek pouch or spinal cord. In young XA animals before onset of glycosuria, renal alpha-galactosidase level was similar to that in age-matched M animals; whereas, their renal beta-galactosidase activity was about 90% of those in the M animals. Partial purification and separation of these enzymes were achieved by chromatography on DEAE-Sepharose CL-6B columns. beta-galactosidase was separated into two isozymes and depression of activity in the XA kidneys was evident in both. alpha-galactosidase was recovered in a single peak. The pH optima of these enzymes from XA and M animals were identical. With p-nitrophenyl glycosides as substrates, the Michaelis constants of these enzymes were also the same of XA and M animals. Molecular weight estimation by gel filtration on Sepharose 6B yielded similar results between M and XA samples: 2.4-10(5) for alpha-galactosidase and 1.6.10(5) and 1.9.10(5) for beta-galactosidase isozymes. The data suggest that the diabetic animals had lower concentrations of alpha-and beta-galactosidase in their kidneys, probably as a consequence of hyperglycemia.", "contents": "Acid glycohydrolase in Chinese hamster with spontaneous diabetes. I. Depressed levels of renal alpha-galactosidase and beta-galactosidase. The activites of alpha-and Beta-galactosidases (alpha-D-galactoside galactohydrolase, EC 3.2.1.22; beta-D-galactoside galactohydrolase, EC 3.2.1.23) were significantly lower in the kidneys of diabetic XA line than those in the nondiabetic M line Chinese hamsters. The depression of these enzymes was found only in the kidney but not in liver, spleen, hind leg muscle, cheek pouch or spinal cord. In young XA animals before onset of glycosuria, renal alpha-galactosidase level was similar to that in age-matched M animals; whereas, their renal beta-galactosidase activity was about 90% of those in the M animals. Partial purification and separation of these enzymes were achieved by chromatography on DEAE-Sepharose CL-6B columns. beta-galactosidase was separated into two isozymes and depression of activity in the XA kidneys was evident in both. alpha-galactosidase was recovered in a single peak. The pH optima of these enzymes from XA and M animals were identical. With p-nitrophenyl glycosides as substrates, the Michaelis constants of these enzymes were also the same of XA and M animals. Molecular weight estimation by gel filtration on Sepharose 6B yielded similar results between M and XA samples: 2.4-10(5) for alpha-galactosidase and 1.6.10(5) and 1.9.10(5) for beta-galactosidase isozymes. The data suggest that the diabetic animals had lower concentrations of alpha-and beta-galactosidase in their kidneys, probably as a consequence of hyperglycemia."}
{"id": "PMID:23849", "title": "Specificity and inhibition studies of Armillaria mellea protease.", "content": "The action of Armillaria mellea protease has been evaluated on a number of polypeptide substrates. It has been shown to split the Pro7-Lys8 bonds in both native and oxidised lysine-vasopressin and the Ser11-Lys12 bond in glucagon. No other splits were detected in these substrates. The enzyme also caused extensive degradation of S-carboxymethyl lysozyme, S-carcoxymethyl pepsinogen and oxidised ribonuclease. A. In each case the only new amino-terminal residue to appear was lysine. A. mellea protease was inhibited by the chelating agents 1,10-phenanthroline, alpha, alpha'-bipyridine and imidazole. The pK1 values (negative log10 of concentration required for 50% inhibition) for these three inhibitors were 3.9, 3.4 and 1.1, respectively. Lysine, S-2-aminoethylcysteine and short chain aliphatic amines also proved to be relatively good inhibitors of A. mellea protease while arginine was a poor inhibitor.", "contents": "Specificity and inhibition studies of Armillaria mellea protease. The action of Armillaria mellea protease has been evaluated on a number of polypeptide substrates. It has been shown to split the Pro7-Lys8 bonds in both native and oxidised lysine-vasopressin and the Ser11-Lys12 bond in glucagon. No other splits were detected in these substrates. The enzyme also caused extensive degradation of S-carboxymethyl lysozyme, S-carcoxymethyl pepsinogen and oxidised ribonuclease. A. In each case the only new amino-terminal residue to appear was lysine. A. mellea protease was inhibited by the chelating agents 1,10-phenanthroline, alpha, alpha'-bipyridine and imidazole. The pK1 values (negative log10 of concentration required for 50% inhibition) for these three inhibitors were 3.9, 3.4 and 1.1, respectively. Lysine, S-2-aminoethylcysteine and short chain aliphatic amines also proved to be relatively good inhibitors of A. mellea protease while arginine was a poor inhibitor."}
{"id": "PMID:23850", "title": "Purification and partial characterization of rat brain acid proteinase (isorenin).", "content": "1. Isorenin was purified 2000-fold from rat brain by a simple 3-step procedure involving affinity chromatography on pepstatinyl-Sepharose, The preparation appears as a homogenous protein in analytical polyacrylamide gel electrophoresis. Sodium dodecyl sulfate gel electrophoresis indicated an apparent molecular weight of 45 000. Isoelectric focusing separated isoenzymes with isoelectric points at pH 5.45, 5.87, 6.16 and 7.05. 2. The enzyme generates antiotensin I from tetradecapeptide (pH optimum 4.7) and from sheep angiotensinogen (pH optima 3.9 and 5.5). The rate of angiotensin I formation from tetradecapeptide was 30 000 times higher than that from sheep angiotensinogen. The enzyme has acid protease activity at pH 3.2 with hemoglobin as the substrate and pepstatin is a potent inhibitor of the enzyme with a Ki of less than 10(-9) M. 3. The properties of the enzyme strongly suggest that it is identical with cathepsin D.", "contents": "Purification and partial characterization of rat brain acid proteinase (isorenin). 1. Isorenin was purified 2000-fold from rat brain by a simple 3-step procedure involving affinity chromatography on pepstatinyl-Sepharose, The preparation appears as a homogenous protein in analytical polyacrylamide gel electrophoresis. Sodium dodecyl sulfate gel electrophoresis indicated an apparent molecular weight of 45 000. Isoelectric focusing separated isoenzymes with isoelectric points at pH 5.45, 5.87, 6.16 and 7.05. 2. The enzyme generates antiotensin I from tetradecapeptide (pH optimum 4.7) and from sheep angiotensinogen (pH optima 3.9 and 5.5). The rate of angiotensin I formation from tetradecapeptide was 30 000 times higher than that from sheep angiotensinogen. The enzyme has acid protease activity at pH 3.2 with hemoglobin as the substrate and pepstatin is a potent inhibitor of the enzyme with a Ki of less than 10(-9) M. 3. The properties of the enzyme strongly suggest that it is identical with cathepsin D."}
{"id": "PMID:23851", "title": "Endogenous substrates for epidermal transglutaminase.", "content": "Potential in vivo substrates for epidermal transglutaminase have been isolated and partially characterized in human stratum corneum and new born rat epidermis. [14C]Putrescine and dansylcadaverine were incorporated into epidermal proteins in vitro. Two high molecular weight proteins incorporated the labels in both the rat ahd human homogenates. One of the proteins was too large to enter a 4% sodium dodecyl sulfate-polyacrylamide spacer gel; the other was seen at the interface between the spacer gel and a 10% sodium dodecyl sulphate-polyacrylamide running gel. These proteins were present in a buffer extract, sodium dodecyl sulphate-dithiothreitol extract and NaOH extract. The labels were also incorporated into protein in the insoluble pellet remaining after the afore-mentioned extractions. The incorporation of putrescine and dansylcadaverine was time dependent, and was inhibited by known inhibitors of epidermal transglutaminase. The two high molecular weight proteins had similar amino acid composition, characterized by high glycine, glutamic acid, serine and aspartic acid. The amino acid composition was similar to, although not identical with, the amino acid composition of alpha-keratin proteins. Epidermal homogenates incubated in the presence of transglutaminase showed progressive insolubilization of the protein. This cross-linking was inhibited by putrescine. [14C]Glycine, [14C]histidine and [4C]proline were incorporated into epidermal proteins in newborn rats in vivo. The glycine-labelled protein became progressively more insoluble when incubated in vitro in the presence of transglutaminase. In vitro incubation with transglutaminase had no effect on the histidine-and proline-labelled proteins.", "contents": "Endogenous substrates for epidermal transglutaminase. Potential in vivo substrates for epidermal transglutaminase have been isolated and partially characterized in human stratum corneum and new born rat epidermis. [14C]Putrescine and dansylcadaverine were incorporated into epidermal proteins in vitro. Two high molecular weight proteins incorporated the labels in both the rat ahd human homogenates. One of the proteins was too large to enter a 4% sodium dodecyl sulfate-polyacrylamide spacer gel; the other was seen at the interface between the spacer gel and a 10% sodium dodecyl sulphate-polyacrylamide running gel. These proteins were present in a buffer extract, sodium dodecyl sulphate-dithiothreitol extract and NaOH extract. The labels were also incorporated into protein in the insoluble pellet remaining after the afore-mentioned extractions. The incorporation of putrescine and dansylcadaverine was time dependent, and was inhibited by known inhibitors of epidermal transglutaminase. The two high molecular weight proteins had similar amino acid composition, characterized by high glycine, glutamic acid, serine and aspartic acid. The amino acid composition was similar to, although not identical with, the amino acid composition of alpha-keratin proteins. Epidermal homogenates incubated in the presence of transglutaminase showed progressive insolubilization of the protein. This cross-linking was inhibited by putrescine. [14C]Glycine, [14C]histidine and [4C]proline were incorporated into epidermal proteins in newborn rats in vivo. The glycine-labelled protein became progressively more insoluble when incubated in vitro in the presence of transglutaminase. In vitro incubation with transglutaminase had no effect on the histidine-and proline-labelled proteins."}
{"id": "PMID:23852", "title": "Studies on (Na+ + K+)-activated ATPase. XLII. Evidence for two classes of essential sulfhydryl groups.", "content": "1. Preincubation of purified (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations from rabbit kidney outer medulla with 5,5'-dithiobis-(2-nitrobenzoic acid) inhibits the (Na+ + 5+)-ATPase and K+-stimulated 4-nitro-phenylphosphatase activities. Phosphorylation of the enzyme by ATP and the Na+-stimulated ATPase activity are inhibited to the same extent as the (Na+ + K+)-ATPase activity, whereas the K+-stimulated 4-nitrophenylphosphatase activity is inhibited much less. 2. Titration with 5,5'-dithiobis-(2-nitrobenzoic acid) in sodium dodecyl sulphate shows the presence of 36 reactive sulfhydryl groups per molecule (Na+ + K+)-ATPase (Mr = 250 000). 3. Treatment with N-ethylmaleimide, resulting in complete inhibition of (Na+ + K+)-ATPase activity, leads to modification of 26 sulfhydryl groups, whereas treatment with 5,5'-dithiobis-(2-nitrobenzoic acid) results in modification of 12 sulfhydryl groups under the same conditions. 4. The reaction of N-ethylmaleimide with an essential SH-group is not prevented by previous blocking of sulfhydryl groups with 5,5'-dithiobis-(2-nitrobenzoic acid). 5. These findings indicate the existence of at least two classes of sulfhydryl groups on the enzyme, each containing at least one vital group. The difference between these classes consists in their different reactivity towards 5,5'-dithiobis-(2-nitrobenzoic acid) and N-ethylmaleimide.", "contents": "Studies on (Na+ + K+)-activated ATPase. XLII. Evidence for two classes of essential sulfhydryl groups. 1. Preincubation of purified (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations from rabbit kidney outer medulla with 5,5'-dithiobis-(2-nitrobenzoic acid) inhibits the (Na+ + 5+)-ATPase and K+-stimulated 4-nitro-phenylphosphatase activities. Phosphorylation of the enzyme by ATP and the Na+-stimulated ATPase activity are inhibited to the same extent as the (Na+ + K+)-ATPase activity, whereas the K+-stimulated 4-nitrophenylphosphatase activity is inhibited much less. 2. Titration with 5,5'-dithiobis-(2-nitrobenzoic acid) in sodium dodecyl sulphate shows the presence of 36 reactive sulfhydryl groups per molecule (Na+ + K+)-ATPase (Mr = 250 000). 3. Treatment with N-ethylmaleimide, resulting in complete inhibition of (Na+ + K+)-ATPase activity, leads to modification of 26 sulfhydryl groups, whereas treatment with 5,5'-dithiobis-(2-nitrobenzoic acid) results in modification of 12 sulfhydryl groups under the same conditions. 4. The reaction of N-ethylmaleimide with an essential SH-group is not prevented by previous blocking of sulfhydryl groups with 5,5'-dithiobis-(2-nitrobenzoic acid). 5. These findings indicate the existence of at least two classes of sulfhydryl groups on the enzyme, each containing at least one vital group. The difference between these classes consists in their different reactivity towards 5,5'-dithiobis-(2-nitrobenzoic acid) and N-ethylmaleimide."}
{"id": "PMID:23854", "title": "Studies on sphingomyelinase of Bacillus cereus. I. Purification and properties.", "content": "A sphingomyelinase was purified 980-fold with recovery of 25.6% from the culture broth of Bacillus cereus, by (NH4)2SO4 precipitation and chromatography on CM-Sephadex, DEAE-cellulose and Sephadex G-75. The purified preparation was free of lipase, protease and other phospholipases. The enzyme specifically hydrolyzed sphingomyelin to ceramide and phosphorylcholine. Lysophosphatidylcholine was also attacked by the enzyme. The enzyme (Mr = 24 000) was maximally active at pH 6-7. Other properties of the enzyme, including hemolytic activity and activation/inhibition studies, are reported.", "contents": "Studies on sphingomyelinase of Bacillus cereus. I. Purification and properties. A sphingomyelinase was purified 980-fold with recovery of 25.6% from the culture broth of Bacillus cereus, by (NH4)2SO4 precipitation and chromatography on CM-Sephadex, DEAE-cellulose and Sephadex G-75. The purified preparation was free of lipase, protease and other phospholipases. The enzyme specifically hydrolyzed sphingomyelin to ceramide and phosphorylcholine. Lysophosphatidylcholine was also attacked by the enzyme. The enzyme (Mr = 24 000) was maximally active at pH 6-7. Other properties of the enzyme, including hemolytic activity and activation/inhibition studies, are reported."}
{"id": "PMID:23855", "title": "Indole to phenolate energy transfer, the alkaline quenching mechanism of beta-trypsin fluorescence.", "content": "Evidence that indole to phenolate energy transfer causes the decrease in beta-trypsin fluorescence with increasing alkalinity is obtained indirectly from viscosity, lifetime, wavelength dependence and chemical modification studies which either exclude or minimize the involvement of other possible mechanisms.", "contents": "Indole to phenolate energy transfer, the alkaline quenching mechanism of beta-trypsin fluorescence. Evidence that indole to phenolate energy transfer causes the decrease in beta-trypsin fluorescence with increasing alkalinity is obtained indirectly from viscosity, lifetime, wavelength dependence and chemical modification studies which either exclude or minimize the involvement of other possible mechanisms."}
{"id": "PMID:23857", "title": "Alkaline isomerization of thermoresistant cytochrome c-552 and horse heart cytochrome c studied by absorption and resonance Raman spectroscopy.", "content": "The structure of the thermoresistant cytochrome c (552, Thermus thermophilus) has been investigated at neutral and alkaline pH by absorption and resonance Raman spectroscopy and compared with that of horse heart cytochrome c. The ligands of the ferricytochrome c-552 at neutral pH are considered to be histidine and methionine, whereas the ligands of ferrocytochrome c-552 are histidine and another nitrogen base, histidine or lysine. Ferric cytochrome c-552 undergoes an alkaline isomerization with a pK of 12.3 (25 degrees C), accompanied by a ligand exchange. Horse heart cytochrome c has at least three isomerization states at alkaline pH (pK 9.3, 12.9 and greater than 13.5 at 25 degrees C). The replacement of the sixth ligand may not be involved in the second isomerization. The thermodynamic parameters for the isomerization were also estimated. The entropy change upon isomerization of cytochrome c-552 is negative, whereas for that of horse heart cytochrome c the entropy change is positive.", "contents": "Alkaline isomerization of thermoresistant cytochrome c-552 and horse heart cytochrome c studied by absorption and resonance Raman spectroscopy. The structure of the thermoresistant cytochrome c (552, Thermus thermophilus) has been investigated at neutral and alkaline pH by absorption and resonance Raman spectroscopy and compared with that of horse heart cytochrome c. The ligands of the ferricytochrome c-552 at neutral pH are considered to be histidine and methionine, whereas the ligands of ferrocytochrome c-552 are histidine and another nitrogen base, histidine or lysine. Ferric cytochrome c-552 undergoes an alkaline isomerization with a pK of 12.3 (25 degrees C), accompanied by a ligand exchange. Horse heart cytochrome c has at least three isomerization states at alkaline pH (pK 9.3, 12.9 and greater than 13.5 at 25 degrees C). The replacement of the sixth ligand may not be involved in the second isomerization. The thermodynamic parameters for the isomerization were also estimated. The entropy change upon isomerization of cytochrome c-552 is negative, whereas for that of horse heart cytochrome c the entropy change is positive."}
{"id": "PMID:23858", "title": "The effect of evolution on homologous proteins: a comparison between the chromophore microenvironments of Italian water buffalo (Bos bubalus, L.) and sperm whale apomyoglobin.", "content": "The perturbing effect of guanidium hydrochloride and pH on the molecular structure of water buffalo apomyoglobin has been investigated by circular dichroism in the far and near ultraviolet and by fluorescence. In the wavelength region between 320 and 260 nm the circular dichroic spectrum of the globin is highly structured and the contributions of the aromatic chromophores have been resolved. Buffalo apomyoglobin undergoes a structural transition at neutral pH which involves elements of the secondary and tertiary structure, as indicated by changes of dichroic activity of the peptide and aromatic chromophores and the fluorescence of the two tryptophanyl residues. The possibility of charge-transfer complex between indole and imidazole is discussed. A major structural transition with abrupt unfolding takes place in the pH region between 5.6 and 4.3. Below pH 4.3 the peptide helical residues, which survive the acid transition, appear to be resistent to further acidification to pH 2.0 while tryptophanyl emission is quenched and shifted to longer wavelengths. A structural transition occurs also in alkali above pH 10, which has been detected by the same techniques. The relationships between buffalo and sperm whale apomyoglobin are discussed.", "contents": "The effect of evolution on homologous proteins: a comparison between the chromophore microenvironments of Italian water buffalo (Bos bubalus, L.) and sperm whale apomyoglobin. The perturbing effect of guanidium hydrochloride and pH on the molecular structure of water buffalo apomyoglobin has been investigated by circular dichroism in the far and near ultraviolet and by fluorescence. In the wavelength region between 320 and 260 nm the circular dichroic spectrum of the globin is highly structured and the contributions of the aromatic chromophores have been resolved. Buffalo apomyoglobin undergoes a structural transition at neutral pH which involves elements of the secondary and tertiary structure, as indicated by changes of dichroic activity of the peptide and aromatic chromophores and the fluorescence of the two tryptophanyl residues. The possibility of charge-transfer complex between indole and imidazole is discussed. A major structural transition with abrupt unfolding takes place in the pH region between 5.6 and 4.3. Below pH 4.3 the peptide helical residues, which survive the acid transition, appear to be resistent to further acidification to pH 2.0 while tryptophanyl emission is quenched and shifted to longer wavelengths. A structural transition occurs also in alkali above pH 10, which has been detected by the same techniques. The relationships between buffalo and sperm whale apomyoglobin are discussed."}
{"id": "PMID:23859", "title": "Activity of nitrogenase and glutamine synthetase in relation to availability of oxygen in continuous cultures of a strain of cowpea Rhizobium sp. supplied with excess ammonium.", "content": "In samples from nitrogen-fixing continuous cultures of strain CB756 of the cowpea type rhizobia (Rhizobium sp.), newly fixed NH+4 is in equiblibrium with the medium, from where it is assimilated by the glutamine synthetase/glutamate synthase pathway. In samples from steady state cultures with different degrees of oxygen-limitation, nitrogenase activity was positively correlated with the biosynthetic of glutamine synthetase in cell free extracts. Also, activities in biosynthetic assays were positively correlated with activities in gamma-glutamyl transferase assays containing 60 mM Mg2+. Relative adenylylation of glutamine synthetase was conveniently measured in cell free extracts as the ratio of gamma-glutamyl transferase activities without and with addition of 60 mM Mg2+. Automatic control of oxygen supply was used to facilitate the study of transitions between steady-state continuous cultures with high and low nitrogenase activities. Adenylylation of glutamine synthetase and repression of nitrogenase activity in the presence of excess NH+4, were masked when oxygen strongly limited culture yield. Partial relief of the limitation in cultures supplied with 10 mM NH+4 produced early decline in nitrogenase activity and increase in relative adenylylation of glutamine synthetase. Decreased oxygen supply produced a rapid decline in relative adenylylation, followed by increased nitrogenase activity, supporting the concept that control of nitrogenase synthesis is modulated by glutamine synthetase adenylylation in these bacteria.", "contents": "Activity of nitrogenase and glutamine synthetase in relation to availability of oxygen in continuous cultures of a strain of cowpea Rhizobium sp. supplied with excess ammonium. In samples from nitrogen-fixing continuous cultures of strain CB756 of the cowpea type rhizobia (Rhizobium sp.), newly fixed NH+4 is in equiblibrium with the medium, from where it is assimilated by the glutamine synthetase/glutamate synthase pathway. In samples from steady state cultures with different degrees of oxygen-limitation, nitrogenase activity was positively correlated with the biosynthetic of glutamine synthetase in cell free extracts. Also, activities in biosynthetic assays were positively correlated with activities in gamma-glutamyl transferase assays containing 60 mM Mg2+. Relative adenylylation of glutamine synthetase was conveniently measured in cell free extracts as the ratio of gamma-glutamyl transferase activities without and with addition of 60 mM Mg2+. Automatic control of oxygen supply was used to facilitate the study of transitions between steady-state continuous cultures with high and low nitrogenase activities. Adenylylation of glutamine synthetase and repression of nitrogenase activity in the presence of excess NH+4, were masked when oxygen strongly limited culture yield. Partial relief of the limitation in cultures supplied with 10 mM NH+4 produced early decline in nitrogenase activity and increase in relative adenylylation of glutamine synthetase. Decreased oxygen supply produced a rapid decline in relative adenylylation, followed by increased nitrogenase activity, supporting the concept that control of nitrogenase synthesis is modulated by glutamine synthetase adenylylation in these bacteria."}
{"id": "PMID:23860", "title": "Enzymatic degradation of succinyl-coenzyme A by rat liver homogenates.", "content": "When a dilute suspension of the mitochondrial fraction of rat liver homogenates was incubated with chemically synthesized succinyl-CoA, a product was rapidly formed which was retained at pH 3.9 on Dowex 50 (H+). Although its acid-base properties were indistinguishable from those of epsilon-aminolevulinic acid, the product did not form a pyrrole with acetylacetone, nor was its enzymatic formation dependent on added glycine. The enzyme which cleaved succinyl-CoA to the epsilon-aminolevulinic acid-like product was inhibited by phenylmethyl sulfonylfluoride. The first substance formed by the peptidase was the unstable thioester of succinic acid and cysteamine which underwent rearrangement to the more stable N-succinyl cysteamine above pH 4.0. It is apparent that the assay of epsilon-aminolevulinic acid synthetase (EC 2.3.1.37) by the ion-exchange method of Ebert et al. (Ebert, P.S., Tschudy, D.P., Choudhry, J.N. and Chirigos, M.A. (1970) Biochim. Biophys. Acta 208, 236--250) can yield erroneous results with succinyl-coenzyme A as substrate, especially when incubations are carried out for less than 25 min.", "contents": "Enzymatic degradation of succinyl-coenzyme A by rat liver homogenates. When a dilute suspension of the mitochondrial fraction of rat liver homogenates was incubated with chemically synthesized succinyl-CoA, a product was rapidly formed which was retained at pH 3.9 on Dowex 50 (H+). Although its acid-base properties were indistinguishable from those of epsilon-aminolevulinic acid, the product did not form a pyrrole with acetylacetone, nor was its enzymatic formation dependent on added glycine. The enzyme which cleaved succinyl-CoA to the epsilon-aminolevulinic acid-like product was inhibited by phenylmethyl sulfonylfluoride. The first substance formed by the peptidase was the unstable thioester of succinic acid and cysteamine which underwent rearrangement to the more stable N-succinyl cysteamine above pH 4.0. It is apparent that the assay of epsilon-aminolevulinic acid synthetase (EC 2.3.1.37) by the ion-exchange method of Ebert et al. (Ebert, P.S., Tschudy, D.P., Choudhry, J.N. and Chirigos, M.A. (1970) Biochim. Biophys. Acta 208, 236--250) can yield erroneous results with succinyl-coenzyme A as substrate, especially when incubations are carried out for less than 25 min."}
{"id": "PMID:23863", "title": "Microcalorimetric method to determine competitive binding. Action of a psychotropic drug (dipotassium chlorazepate) on L-tryptophan . human serum albumin complex.", "content": "A mathematical treatment and an original microcalorimetric method are developed to verify an eventual competitive binding between any two substances for the same macromolecule. To apply this method, a competitive binding of L-tryptophan and one benzodiazepin (dipotassium chlorazepate) for human serum albumin is perfectly demonstrated. The association constants and the enthalpy variations are equal to 14 000 +/- 2000 M-1 and --6.6 +/- 0.2 kcal/mol for human serum albumin . tryptophan complex and 13 000 +/- 1000 M-1 and --10.0 +/- 0.2 kcal/mol for human serum albumin . chlorazepate complex. In all cases the stoichiometry is equal to one. The binding of tryptophan to human serum albumin is partially stereospecific; the association constant and the enthalpy variation for D-tryptophan complex are equal, respectively, to 1000 +/- 200 M-1 and --2.6 +/- 0.3 kcal/mol.", "contents": "Microcalorimetric method to determine competitive binding. Action of a psychotropic drug (dipotassium chlorazepate) on L-tryptophan . human serum albumin complex. A mathematical treatment and an original microcalorimetric method are developed to verify an eventual competitive binding between any two substances for the same macromolecule. To apply this method, a competitive binding of L-tryptophan and one benzodiazepin (dipotassium chlorazepate) for human serum albumin is perfectly demonstrated. The association constants and the enthalpy variations are equal to 14 000 +/- 2000 M-1 and --6.6 +/- 0.2 kcal/mol for human serum albumin . tryptophan complex and 13 000 +/- 1000 M-1 and --10.0 +/- 0.2 kcal/mol for human serum albumin . chlorazepate complex. In all cases the stoichiometry is equal to one. The binding of tryptophan to human serum albumin is partially stereospecific; the association constant and the enthalpy variation for D-tryptophan complex are equal, respectively, to 1000 +/- 200 M-1 and --2.6 +/- 0.3 kcal/mol."}
{"id": "PMID:23864", "title": "Interactions between chondroitin sulfate and concanavalin A.", "content": "Chondroitin sulfate, the major extracellular matrix glycosaminoglycan, formed an insoluble complex with concanavalin A at pH 5.4 or below. Concanavalin A (500 microgram/ml) reacted only within a relatively narrow concentration range of chondroitin sulfate (optimally between 5 and 50 microgram/ml) at pH 5.4 in 0.05 M buffer. Similar precipitin-like interactions were seen between concanavalin A and hyaluronic acid or heparin. No precipitating complexes formed between concanavalin A and the glycosaminoglycans at these concentrations in physiological salt solutions (approx. 0.15 M) unless the pH was below 4.5. Precipitating self-aggregates of concanavalin A appeared to be promoted by chondroitin sulfate at pH 7.3, but no significant precipitation occurred between the reactants at this pH even at very high concentrations, nor did soluble complexes form as determined by affinity chromatography on Sephadex G-200 or fractionation on Bio-Gel P-200. Thus, binding between the lectin and glycosaminoglycans appeared to depend upon reversible non-specific electrostatic interactions observed only at low Ph and low ionic strength. Stable interactions were not seen in experiments using physiologically balanced salts at near neutral pH.", "contents": "Interactions between chondroitin sulfate and concanavalin A. Chondroitin sulfate, the major extracellular matrix glycosaminoglycan, formed an insoluble complex with concanavalin A at pH 5.4 or below. Concanavalin A (500 microgram/ml) reacted only within a relatively narrow concentration range of chondroitin sulfate (optimally between 5 and 50 microgram/ml) at pH 5.4 in 0.05 M buffer. Similar precipitin-like interactions were seen between concanavalin A and hyaluronic acid or heparin. No precipitating complexes formed between concanavalin A and the glycosaminoglycans at these concentrations in physiological salt solutions (approx. 0.15 M) unless the pH was below 4.5. Precipitating self-aggregates of concanavalin A appeared to be promoted by chondroitin sulfate at pH 7.3, but no significant precipitation occurred between the reactants at this pH even at very high concentrations, nor did soluble complexes form as determined by affinity chromatography on Sephadex G-200 or fractionation on Bio-Gel P-200. Thus, binding between the lectin and glycosaminoglycans appeared to depend upon reversible non-specific electrostatic interactions observed only at low Ph and low ionic strength. Stable interactions were not seen in experiments using physiologically balanced salts at near neutral pH."}
{"id": "PMID:23865", "title": "Regulation of thyroid hormone metabolism in rat liver fractions.", "content": "The nature of the conversion of thyroxine (T4) to triiodothyronine (T3) and reverse triiodothyronine (rT3) was investigated in rat liver homogenate and microsomes. A 6-fold rise of T3 and 2.5-fold rise of rT3 levels determined by specific radioimmunoassays was observed over 6 h after the addition of T4. An enzymic process is suggested that converts T4 to T3 and rT3. For T3 the optimal pH is 6 and for rT3, 9.5. The converting activity for both T3 and rT3 is temperature dependent and can be suppressed by heat, H2O2, merthiolate and by 5-propyl-2-thiouracil. rT3 and to a lesser degree iodide, were able to inhibit the production of T3 in a dose related fashion. Therefore the pH dependency, rT3 and iodide may regulate the availability of T3 or rT3 depending on the metabolic requirements of thyroid hormones.", "contents": "Regulation of thyroid hormone metabolism in rat liver fractions. The nature of the conversion of thyroxine (T4) to triiodothyronine (T3) and reverse triiodothyronine (rT3) was investigated in rat liver homogenate and microsomes. A 6-fold rise of T3 and 2.5-fold rise of rT3 levels determined by specific radioimmunoassays was observed over 6 h after the addition of T4. An enzymic process is suggested that converts T4 to T3 and rT3. For T3 the optimal pH is 6 and for rT3, 9.5. The converting activity for both T3 and rT3 is temperature dependent and can be suppressed by heat, H2O2, merthiolate and by 5-propyl-2-thiouracil. rT3 and to a lesser degree iodide, were able to inhibit the production of T3 in a dose related fashion. Therefore the pH dependency, rT3 and iodide may regulate the availability of T3 or rT3 depending on the metabolic requirements of thyroid hormones."}
{"id": "PMID:23866", "title": "Differences between human and rabbit transferrins.", "content": "Rabbit reticulocyte incorporation of iron from rabbit transferrin was independent of transferrin iron saturation but uptake from human transferrin was saturation dependent. Unlike human transferrin, rabbit transferrin does not surrender its iron from any unique preferred iron-binding site and can be described as functionally homogeneic. The two proteins also differ in their acid-base iron-binding properties. One human transferrin iron binding site retains an ability to bind iron at somewhat acid pH but this property is not shared by rabbit transferrin.", "contents": "Differences between human and rabbit transferrins. Rabbit reticulocyte incorporation of iron from rabbit transferrin was independent of transferrin iron saturation but uptake from human transferrin was saturation dependent. Unlike human transferrin, rabbit transferrin does not surrender its iron from any unique preferred iron-binding site and can be described as functionally homogeneic. The two proteins also differ in their acid-base iron-binding properties. One human transferrin iron binding site retains an ability to bind iron at somewhat acid pH but this property is not shared by rabbit transferrin."}
{"id": "PMID:23867", "title": "The interactions of gallium with various buffers and chelating agents in aqueous solution: gallium-71 and hydrogen-1 NMR studies.", "content": "The interactions of gallium (Ga) with the ligands, EDTA, NTA, phosphate, lactate, MOPS, TRIS and HEPES are investigated using both 71Ga and 1H nmr measurements. Both EDTA and NTA form strong complexes with gallium, which have a 1:1 stoichiometry. In alkaline solution the tetrahedral Ga(OD)4- competes strongly with EDTA in complex formation. In the lactate complex, there are probably three lactates per gallium present. The phosphate complexes of gallium are difficult to characterize on the basis of this investigation. The buffers, MOPS, TRIS, and HEPES, do not interact with gallium significantly. The ability of the ligands to bind gallium correlates well with their ability to inhibit gallium incorporation by L1210 leukemic cells.", "contents": "The interactions of gallium with various buffers and chelating agents in aqueous solution: gallium-71 and hydrogen-1 NMR studies. The interactions of gallium (Ga) with the ligands, EDTA, NTA, phosphate, lactate, MOPS, TRIS and HEPES are investigated using both 71Ga and 1H nmr measurements. Both EDTA and NTA form strong complexes with gallium, which have a 1:1 stoichiometry. In alkaline solution the tetrahedral Ga(OD)4- competes strongly with EDTA in complex formation. In the lactate complex, there are probably three lactates per gallium present. The phosphate complexes of gallium are difficult to characterize on the basis of this investigation. The buffers, MOPS, TRIS, and HEPES, do not interact with gallium significantly. The ability of the ligands to bind gallium correlates well with their ability to inhibit gallium incorporation by L1210 leukemic cells."}
{"id": "PMID:23868", "title": "Formation and spectral characterization of Cu(II)-poly(L-ornithine) complexes.", "content": "Cu(II)-Poly-(1-ornithine) complexes in aqueous solution have been studied using potentiometric titration and absorption and circular dichroism spectra. As in the case of Cu(II)-poly(L-arginine) complexes studied previously, two types of compounds have been detected, labeled complexes I and II. Complex I contains two amine nitrogens and two water molecules coordinated to the copper. Complex II, two amine and two amide nitrogens. Amide nitrogen coordination confers optical activity to the copper d-d transitions. Furthermore, amine and amide nitrogen coordination to the copper are characterized by charge transfer transitions at 250 and 320 nm respectively which were already identified in Cu(II)-poly(L-arginine) systems.", "contents": "Formation and spectral characterization of Cu(II)-poly(L-ornithine) complexes. Cu(II)-Poly-(1-ornithine) complexes in aqueous solution have been studied using potentiometric titration and absorption and circular dichroism spectra. As in the case of Cu(II)-poly(L-arginine) complexes studied previously, two types of compounds have been detected, labeled complexes I and II. Complex I contains two amine nitrogens and two water molecules coordinated to the copper. Complex II, two amine and two amide nitrogens. Amide nitrogen coordination confers optical activity to the copper d-d transitions. Furthermore, amine and amide nitrogen coordination to the copper are characterized by charge transfer transitions at 250 and 320 nm respectively which were already identified in Cu(II)-poly(L-arginine) systems."}
{"id": "PMID:23869", "title": "[Activation parameters for the cleavage reaction of cytidine-2',3'-monophosphate catalyzed by Penicillium brevicompactum and Aspergillus clavatus RNAses].", "content": "On the basis of coincidence of all activation parameters (E, deltaH*, deltaF* and deltaS*) for the reaction of cleavage of cytidine-2';3'-monophosphate catalyzed by \"acid\" (pH-optimum 4.7) nonspecific RNAses from Aspergillus clavatus and Penicillium brevicompactum (EC 3. 1. 4. 23) it has been proposed that the mechanism of action on this reaction stage (hydrolysis) for both enzymes is equal.", "contents": "[Activation parameters for the cleavage reaction of cytidine-2',3'-monophosphate catalyzed by Penicillium brevicompactum and Aspergillus clavatus RNAses]. On the basis of coincidence of all activation parameters (E, deltaH*, deltaF* and deltaS*) for the reaction of cleavage of cytidine-2';3'-monophosphate catalyzed by \"acid\" (pH-optimum 4.7) nonspecific RNAses from Aspergillus clavatus and Penicillium brevicompactum (EC 3. 1. 4. 23) it has been proposed that the mechanism of action on this reaction stage (hydrolysis) for both enzymes is equal."}
{"id": "PMID:23870", "title": "[Kinetics of N-dealkylation of amines with participation of microsomal cytochrome P-450].", "content": "Within the temperature range of 20-37 degrees C the kinetics of the demethylation reactions of a variety of amines with participation of hepatic microsomal cytochrome P-450, NADPH and O2 has been studied. Catalytical rate constants for all the substrates have been determined in generalized forms. Activation parameters deltaH* and deltaS* are also estimated. There is a linear relationship between deltaH* and deltaS*: deltaH*=20.7 kcal+366 degrees K deltaS*. Compensation relationship is characterized by a coefficient alpha=366 degrees/Taverage=1.21. The nature of the limiting step of the enzymatic amine demethylation involving cytochrome P-450 of hepatic microsomes is discussed.", "contents": "[Kinetics of N-dealkylation of amines with participation of microsomal cytochrome P-450]. Within the temperature range of 20-37 degrees C the kinetics of the demethylation reactions of a variety of amines with participation of hepatic microsomal cytochrome P-450, NADPH and O2 has been studied. Catalytical rate constants for all the substrates have been determined in generalized forms. Activation parameters deltaH* and deltaS* are also estimated. There is a linear relationship between deltaH* and deltaS*: deltaH*=20.7 kcal+366 degrees K deltaS*. Compensation relationship is characterized by a coefficient alpha=366 degrees/Taverage=1.21. The nature of the limiting step of the enzymatic amine demethylation involving cytochrome P-450 of hepatic microsomes is discussed."}
{"id": "PMID:23871", "title": "[Catalytic properties of three isoenzymes possessing pyrophosphatase activity, isolated from baker's yeast].", "content": "A kinetic study of inorganic pyrophosphatase isolated from brewer's yeast was done. It was shown that all three isoenzymes have the same pH-optimum and specificity with respect to substrate and metal activator. Statistical treatment of the kinetic data yielded equilibrium and catalytical constants, describing enzyme interaction with the metal activator and substrate. The catalytic properties of all three isoenzymes are similar to those of the baker's yeast pyrophosphatase. The fluoride inhibition pattern for inorganic pyrophosphatase from brewer's yeast is similar to that for the baker's yeast enzyme.", "contents": "[Catalytic properties of three isoenzymes possessing pyrophosphatase activity, isolated from baker's yeast]. A kinetic study of inorganic pyrophosphatase isolated from brewer's yeast was done. It was shown that all three isoenzymes have the same pH-optimum and specificity with respect to substrate and metal activator. Statistical treatment of the kinetic data yielded equilibrium and catalytical constants, describing enzyme interaction with the metal activator and substrate. The catalytic properties of all three isoenzymes are similar to those of the baker's yeast pyrophosphatase. The fluoride inhibition pattern for inorganic pyrophosphatase from brewer's yeast is similar to that for the baker's yeast enzyme."}
{"id": "PMID:23873", "title": "Preliminary studies with L-asparaginase bound to implantable bovine collagen heterografts: a potential long-term, sustained dosage, antitumor enzyme therapy system.", "content": "In this study, L-Asparaginase has been bound to collagen heterografts derived from carotid bovine arteries. The immobilization procedure utilizes both non-covalent and covalent interactions to fix the enzyme. Binding of the enzyme to the graft material was shown to the pH dependent, with optimum binding occurring at pH 6.0 and pH 8.5. Amidohydrolysis by the bound enzyme exhibited zero-order kinetic behavior at substrate saturating conditions. Total apparent asparaginase activity expressed by the grafts as a function of the number of repeated in vitro assay trials demonstrated that over a span of 3 months of intermittent storage and use, the enzyme-grafts retained as much as 62% of their initial activities. Implantation of 4 asparaginase-collagen grafts in various locations of the thoracic and abdominal aorta resulting in prolonged reductions of plasma asparagine levels in 3 of the 4 implants. Presence of plasma asparaginase was checked in one of the four implants and determined to be less than 2 X 10(-4) I.U./ml. Removal of grafts from 3 of the 4 animal subjects showed reductions in the apparent asparaginase activity expressed by the grafts of 7 to 70 percent after in vivo contact times which varied from 6 to 15 days.", "contents": "Preliminary studies with L-asparaginase bound to implantable bovine collagen heterografts: a potential long-term, sustained dosage, antitumor enzyme therapy system. In this study, L-Asparaginase has been bound to collagen heterografts derived from carotid bovine arteries. The immobilization procedure utilizes both non-covalent and covalent interactions to fix the enzyme. Binding of the enzyme to the graft material was shown to the pH dependent, with optimum binding occurring at pH 6.0 and pH 8.5. Amidohydrolysis by the bound enzyme exhibited zero-order kinetic behavior at substrate saturating conditions. Total apparent asparaginase activity expressed by the grafts as a function of the number of repeated in vitro assay trials demonstrated that over a span of 3 months of intermittent storage and use, the enzyme-grafts retained as much as 62% of their initial activities. Implantation of 4 asparaginase-collagen grafts in various locations of the thoracic and abdominal aorta resulting in prolonged reductions of plasma asparagine levels in 3 of the 4 implants. Presence of plasma asparaginase was checked in one of the four implants and determined to be less than 2 X 10(-4) I.U./ml. Removal of grafts from 3 of the 4 animal subjects showed reductions in the apparent asparaginase activity expressed by the grafts of 7 to 70 percent after in vivo contact times which varied from 6 to 15 days."}
{"id": "PMID:23874", "title": "Relation of the acid concentration of the parietal component of the gastric juice to the maximal acid output in man.", "content": "In two populations of patients tested with S.C. histamine and with I.V. pentagastrin the values of the theoretical acid [H+]O and chloride [Cl-]O concentration of the parietal secretion for a zero value of sodium from the relationships H+ = f ([Na+]) and Cl- = f ([Na+]) were calculated. In both populations a decrease of [H+]O and [Cl-]o for low acid outputs was observed. The parallel decrease of the calculated H+ and Cl- ion concentration of the parietal component for low acid outputs gives indirect evidence that parietal secretion could become hypotonic in patients whose acid output is low.", "contents": "Relation of the acid concentration of the parietal component of the gastric juice to the maximal acid output in man. In two populations of patients tested with S.C. histamine and with I.V. pentagastrin the values of the theoretical acid [H+]O and chloride [Cl-]O concentration of the parietal secretion for a zero value of sodium from the relationships H+ = f ([Na+]) and Cl- = f ([Na+]) were calculated. In both populations a decrease of [H+]O and [Cl-]o for low acid outputs was observed. The parallel decrease of the calculated H+ and Cl- ion concentration of the parietal component for low acid outputs gives indirect evidence that parietal secretion could become hypotonic in patients whose acid output is low."}
{"id": "PMID:23875", "title": "Preparation and properties of proteases immobilized on anion exchange resin with glutaraldehyde.", "content": "High activity alkaline protease was obtained when the enzyme was immobilized on Dowex MWA-1 (mesh 20-50) with 10% glutaraldehyde in chilled phosphate buffer (M/15, PH 6.5). Activity yields of the protease and rennet were 27 and 29, respectively. The highest activities appeared at 60 degrees C, pH 10 for alkaline protease and 50 degrees C, pH 4.0 for rennet. The properties of both proteases were not essentially changed by the immobilization except that the Km values of both enzymes were increased about tenfold as a result of immobilization. Both proteases in the immobilized state were more stable than those in the free state at 60 degrees C. Other peptide hydrolases, beta-galactosidase, invertase, and glucoamylase, were successfully immobilized with high activities, but lipase, hexokinase, glucose-6-phosphate dehydrogenase, and xanthine oxidase became inactive.", "contents": "Preparation and properties of proteases immobilized on anion exchange resin with glutaraldehyde. High activity alkaline protease was obtained when the enzyme was immobilized on Dowex MWA-1 (mesh 20-50) with 10% glutaraldehyde in chilled phosphate buffer (M/15, PH 6.5). Activity yields of the protease and rennet were 27 and 29, respectively. The highest activities appeared at 60 degrees C, pH 10 for alkaline protease and 50 degrees C, pH 4.0 for rennet. The properties of both proteases were not essentially changed by the immobilization except that the Km values of both enzymes were increased about tenfold as a result of immobilization. Both proteases in the immobilized state were more stable than those in the free state at 60 degrees C. Other peptide hydrolases, beta-galactosidase, invertase, and glucoamylase, were successfully immobilized with high activities, but lipase, hexokinase, glucose-6-phosphate dehydrogenase, and xanthine oxidase became inactive."}
{"id": "PMID:23876", "title": "A new method for cell immobilization.", "content": "A new method for producing particles and membranes containing immobilized bacteria is presented. These immobilized bacteria display good stability over time making them well suited for use in a packed-bed reactor. Such a reactor is tested as a function of the different parameters of the system. The results are qualitatively similar to those obtained with purified enzyme reactors, but some discrepancies with the plug-flow model are noted. It is necessary to use a more sophisticated model in order to fit the experimental data.", "contents": "A new method for cell immobilization. A new method for producing particles and membranes containing immobilized bacteria is presented. These immobilized bacteria display good stability over time making them well suited for use in a packed-bed reactor. Such a reactor is tested as a function of the different parameters of the system. The results are qualitatively similar to those obtained with purified enzyme reactors, but some discrepancies with the plug-flow model are noted. It is necessary to use a more sophisticated model in order to fit the experimental data."}
{"id": "PMID:23877", "title": "Isolation of lysozyme on chitosan.", "content": "Lysozyme has been immobilized on chitosan, a polyaminosaccharide, without using any intermediate reagent. The best pH conditions for operating the chitosan columns have been determined and the best eluting agent was found to be a 2% solution of propylamine. The lysozyme activity was determined after reacting lysozyme with the product of glycolchitin and Remazol Brilliant Blue R. The recovery of lysozyme from chicken egg white yields lysozyme with 55% activity.", "contents": "Isolation of lysozyme on chitosan. Lysozyme has been immobilized on chitosan, a polyaminosaccharide, without using any intermediate reagent. The best pH conditions for operating the chitosan columns have been determined and the best eluting agent was found to be a 2% solution of propylamine. The lysozyme activity was determined after reacting lysozyme with the product of glycolchitin and Remazol Brilliant Blue R. The recovery of lysozyme from chicken egg white yields lysozyme with 55% activity."}
{"id": "PMID:23878", "title": "[Effect of cholinolytic and adrenergic blocking preparations on rat erythrocyte resistance to hypo-osmotic hemolysis].", "content": "The influence of central cholinolytics and adrenoblocking drugs on the hemolysis of rat erythrocytes in the hypoosmotic buffer was studied in vitro. At pH 7.4 in a concentration of 10(-4) M central cholinolytics ethyl-dipracil, diphacil, pediphen, tropacin, and beta-adrenoblocking agent propranolol protected the erythrocytes from hemolysis most intensively. The central M-cholinlytics amizyl, glypin, and alpha-adrenoblocking agents purroxan, sympatholytin, phentolamin were less active. The antihemolytic effect of drugs reached the maximum in the course of 30 minutes, and was maintained for several hours. The protection of erythrocytes from hemolysis by drugs containing tertiary nitrogen was greater. Prevention of the hypoosmotic hemolysis pointed to the stabilization of the erythrocyte membrane by the preparations examined. In the mechanism of action of the central N-cholinolytics and beta-adrenoblocking drugs it is necessary to consider the possibility of stabilization of the membrane formations containing no synaptic contacts.", "contents": "[Effect of cholinolytic and adrenergic blocking preparations on rat erythrocyte resistance to hypo-osmotic hemolysis]. The influence of central cholinolytics and adrenoblocking drugs on the hemolysis of rat erythrocytes in the hypoosmotic buffer was studied in vitro. At pH 7.4 in a concentration of 10(-4) M central cholinolytics ethyl-dipracil, diphacil, pediphen, tropacin, and beta-adrenoblocking agent propranolol protected the erythrocytes from hemolysis most intensively. The central M-cholinlytics amizyl, glypin, and alpha-adrenoblocking agents purroxan, sympatholytin, phentolamin were less active. The antihemolytic effect of drugs reached the maximum in the course of 30 minutes, and was maintained for several hours. The protection of erythrocytes from hemolysis by drugs containing tertiary nitrogen was greater. Prevention of the hypoosmotic hemolysis pointed to the stabilization of the erythrocyte membrane by the preparations examined. In the mechanism of action of the central N-cholinolytics and beta-adrenoblocking drugs it is necessary to consider the possibility of stabilization of the membrane formations containing no synaptic contacts."}
{"id": "PMID:23879", "title": "[Graft-versus-host reaction following granulocyte transfusion from a normal donor (author's transl)].", "content": "Graft-versus-Host disease following the transfusion of leukocytes from normal donor occured during remission-reinduction therapy in a 5 years old girl with acute lymphocytic leukemia. The clinical picture consisting of rash, diarrhea and somnolence was congruent with the diagnosis. Graft-versus-Host disease was confirmed by histology of skin biopsy and exclusion of other causes. The child survived the disease. We recommend the irradiation of leukocyte concentrates before transfusion.", "contents": "[Graft-versus-host reaction following granulocyte transfusion from a normal donor (author's transl)]. Graft-versus-Host disease following the transfusion of leukocytes from normal donor occured during remission-reinduction therapy in a 5 years old girl with acute lymphocytic leukemia. The clinical picture consisting of rash, diarrhea and somnolence was congruent with the diagnosis. Graft-versus-Host disease was confirmed by histology of skin biopsy and exclusion of other causes. The child survived the disease. We recommend the irradiation of leukocyte concentrates before transfusion."}
{"id": "PMID:23880", "title": "Responses of rabbit portal vein to histamine.", "content": "1 Histamine produced a dose-dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6-hydroxy-dopamine, nor by pretreatment of the rabbit with reserpine. 2 The response to histamine was blocked by H1-receptor antagonists only when the blocking agent was used in very high concentrations, and was not antagonized by the H2-receptor blocking agent, metiamide, H1-receptor antagonists did not block the effects of 5-hydroxytryptamine. 3 The contractions elicited by histamine, 5-hydroxytryptamine and noradrenaline were blocked by phentolamine. 4 Desensitization to high doses of 5-hydroxytryptamine caused a concomitant depression in the response to histamine but not to noradrenaline or acetylcholine. 5 The results suggest that the contractions of rabbit portal vein elicited by histamine are not mediated by receptors of the H1- or the H2-type, but may involve an action of histamine at a receptor which is also involved in the action of 5-hydroxytryptamine.", "contents": "Responses of rabbit portal vein to histamine. 1 Histamine produced a dose-dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6-hydroxy-dopamine, nor by pretreatment of the rabbit with reserpine. 2 The response to histamine was blocked by H1-receptor antagonists only when the blocking agent was used in very high concentrations, and was not antagonized by the H2-receptor blocking agent, metiamide, H1-receptor antagonists did not block the effects of 5-hydroxytryptamine. 3 The contractions elicited by histamine, 5-hydroxytryptamine and noradrenaline were blocked by phentolamine. 4 Desensitization to high doses of 5-hydroxytryptamine caused a concomitant depression in the response to histamine but not to noradrenaline or acetylcholine. 5 The results suggest that the contractions of rabbit portal vein elicited by histamine are not mediated by receptors of the H1- or the H2-type, but may involve an action of histamine at a receptor which is also involved in the action of 5-hydroxytryptamine."}
{"id": "PMID:23881", "title": "Release of noradrenaline from cat spleen slices by potassium.", "content": "1 When cat spleen slices were exposed to a potassium-enriched (140 mM) Krebs solution, 367 +/- 31 ng g-1 5 min-1 of noradrenaline (NA) was released into the bathing medium. 2 Phenylephrine and clonidine (10(-7) to 10(-3) M) did not significantly modify the potassium-evoked NA release; acetylcholine decreased it in a dose-dependent manner. 3 Phenoxybenzamine increased NA release by 50% but phentolamine did not alter it; high concentrations of this drug greatly decreased NA release. Cocaine increased the NA release by about 30%. 4 It is suggested that the failure of sympathomimetic amines to depress, and of alpha-adrenoceptor blocking agents to enhance the release of NA by high potassium concentrations may be related to prolonged depolarization of the nerve terminals, which may desensitize presynaptic alpha-receptors. The fact that the same drugs are able to modify NA release during electrical nerve stimulation may be ascribed to the much shorter periods of depolarization occurring under these conditions.", "contents": "Release of noradrenaline from cat spleen slices by potassium. 1 When cat spleen slices were exposed to a potassium-enriched (140 mM) Krebs solution, 367 +/- 31 ng g-1 5 min-1 of noradrenaline (NA) was released into the bathing medium. 2 Phenylephrine and clonidine (10(-7) to 10(-3) M) did not significantly modify the potassium-evoked NA release; acetylcholine decreased it in a dose-dependent manner. 3 Phenoxybenzamine increased NA release by 50% but phentolamine did not alter it; high concentrations of this drug greatly decreased NA release. Cocaine increased the NA release by about 30%. 4 It is suggested that the failure of sympathomimetic amines to depress, and of alpha-adrenoceptor blocking agents to enhance the release of NA by high potassium concentrations may be related to prolonged depolarization of the nerve terminals, which may desensitize presynaptic alpha-receptors. The fact that the same drugs are able to modify NA release during electrical nerve stimulation may be ascribed to the much shorter periods of depolarization occurring under these conditions."}
{"id": "PMID:23882", "title": "An in vitro comparison of beta-adrenoceptor stimulants on potassium-depolarized uterine preparations from guinea-pigs.", "content": "1 A comparison of six beta-adrenoceptor stimulants has been carried out on in vitro preparations of guinea-pig uterus which were depolarized in K(+)-Krebs solution. Results have also been obtained on uterine preparations in which contractions to acetylcholine were inhibited. The establishment of the conditions for the K(+)-depolarized preparations are described.2 There was no significant difference between potency values (mean neg log EC(50) values) for any of the drugs on the two types of uterine preparation i.e. the preparations had the same sensitivity to the drugs.3 There was a less than two-fold difference between the relative potency values for the beta-adrenoceptor stimulants on the two types of uterine preparation. The relative potency values (isoprenaline = 100) on the K(+)-depolarized preparation were fenoterol 74.1, salbutamol 15.1, rimiterol 13.5, terbutaline 8.2 and orciprenaline 5.6.4 The relative potency values obtained on uterine preparations were less than three-fold different from those previously found for guinea-pig trachea (after inhibition of extraneuronal uptake).5 The pA(2) value for propranolol on the K(+)-depolarized uterine preparations was 9.13.6 It is concluded that the K(+)-depolarized guinea-pig uterine preparation can be used for quantitative studies on beta-adrenoceptor stimulant drugs. It lacks spontaneous activity, drugs can be added cumulatively and several drugs can be compared on a single preparation. In addition, the results obtained support the classification of the beta-adrenoceptors in guinea-pig uterus and trachea in the same sub-group (beta(2)).", "contents": "An in vitro comparison of beta-adrenoceptor stimulants on potassium-depolarized uterine preparations from guinea-pigs. 1 A comparison of six beta-adrenoceptor stimulants has been carried out on in vitro preparations of guinea-pig uterus which were depolarized in K(+)-Krebs solution. Results have also been obtained on uterine preparations in which contractions to acetylcholine were inhibited. The establishment of the conditions for the K(+)-depolarized preparations are described.2 There was no significant difference between potency values (mean neg log EC(50) values) for any of the drugs on the two types of uterine preparation i.e. the preparations had the same sensitivity to the drugs.3 There was a less than two-fold difference between the relative potency values for the beta-adrenoceptor stimulants on the two types of uterine preparation. The relative potency values (isoprenaline = 100) on the K(+)-depolarized preparation were fenoterol 74.1, salbutamol 15.1, rimiterol 13.5, terbutaline 8.2 and orciprenaline 5.6.4 The relative potency values obtained on uterine preparations were less than three-fold different from those previously found for guinea-pig trachea (after inhibition of extraneuronal uptake).5 The pA(2) value for propranolol on the K(+)-depolarized uterine preparations was 9.13.6 It is concluded that the K(+)-depolarized guinea-pig uterine preparation can be used for quantitative studies on beta-adrenoceptor stimulant drugs. It lacks spontaneous activity, drugs can be added cumulatively and several drugs can be compared on a single preparation. In addition, the results obtained support the classification of the beta-adrenoceptors in guinea-pig uterus and trachea in the same sub-group (beta(2))."}
{"id": "PMID:23884", "title": "In vivo release of gastrin into human gastric juice.", "content": "The release of antral gastrin has been examined in human subjects by infusing saline and albumin into their stomachs. Immunoreactive gastrin (IRG) was present in fasting serum but not in fasting gastric juice. Intragastric infusions of saline and albumin induced small but significant (P less than 0.05) rises in the serum concentrations of IRG. There was no significant difference between the magnitude of the serum gastrin responses to these two stimuli. The stimuli induced a rise in the luminal concentration of IRG which was sixfold greater than that in the serum concentration of IRG. The response to albumin was significantly greater than the response to saline (P less than 0.05). The IRG in gastric juice was chromatographically similar to heptadecapeptide gastrin. The stimuli also released IRG in patients with duodenal ulcers. The magnitude of the release into serum and gastric juice in these patients was significantly reduced by antrectomy (P less than 0.05).", "contents": "In vivo release of gastrin into human gastric juice. The release of antral gastrin has been examined in human subjects by infusing saline and albumin into their stomachs. Immunoreactive gastrin (IRG) was present in fasting serum but not in fasting gastric juice. Intragastric infusions of saline and albumin induced small but significant (P less than 0.05) rises in the serum concentrations of IRG. There was no significant difference between the magnitude of the serum gastrin responses to these two stimuli. The stimuli induced a rise in the luminal concentration of IRG which was sixfold greater than that in the serum concentration of IRG. The response to albumin was significantly greater than the response to saline (P less than 0.05). The IRG in gastric juice was chromatographically similar to heptadecapeptide gastrin. The stimuli also released IRG in patients with duodenal ulcers. The magnitude of the release into serum and gastric juice in these patients was significantly reduced by antrectomy (P less than 0.05)."}
{"id": "PMID:23890", "title": "Studies on the avian shell gland during egg formation: mucosal intracellular pH.", "content": "1. The intracellular pH and the extracellular fluid volume of the shell gland mucosa were determined. 2. The pH value varied little during egg formation, the overall mean being 7.11 +/- 0.02 (n = 34). 3. The lowest pH, 7.01, was found 10 h after oviposition and the highest, 7.22, 18 h after oviposition.", "contents": "Studies on the avian shell gland during egg formation: mucosal intracellular pH. 1. The intracellular pH and the extracellular fluid volume of the shell gland mucosa were determined. 2. The pH value varied little during egg formation, the overall mean being 7.11 +/- 0.02 (n = 34). 3. The lowest pH, 7.01, was found 10 h after oviposition and the highest, 7.22, 18 h after oviposition."}
{"id": "PMID:23891", "title": "Gastric volume and pH in out-patients.", "content": "We measured the volume and pH of the gastric content of 21 out-patients and 21 in-patients under general anaesthesia. Gastric tubes were inserted after induction of anaesthesia, and gastric fluids were withdrawn for pH determinations. Gastric volumes were measured by a dilution technique using polyethylene glycol as the indicator and also by measurement of the volume aspirated through a gastrict tube. Out-patients had a mean gastric volume of 69 +/- 17 ml while in-patients had a mean volume of 33 +/- 4 ml. The average gastric pH for the out-patients was 1.8 +/- 0.2 and for the in-patients 2.0 +/- 0.3. Four out-patients had more than 75 ml of gastric fluid of pH less than 2.0. Aspiration through a gastrict tube did not empty the stomach completely and the volume thus obtained gave a falsely low estimate of the gastric volume.", "contents": "Gastric volume and pH in out-patients. We measured the volume and pH of the gastric content of 21 out-patients and 21 in-patients under general anaesthesia. Gastric tubes were inserted after induction of anaesthesia, and gastric fluids were withdrawn for pH determinations. Gastric volumes were measured by a dilution technique using polyethylene glycol as the indicator and also by measurement of the volume aspirated through a gastrict tube. Out-patients had a mean gastric volume of 69 +/- 17 ml while in-patients had a mean volume of 33 +/- 4 ml. The average gastric pH for the out-patients was 1.8 +/- 0.2 and for the in-patients 2.0 +/- 0.3. Four out-patients had more than 75 ml of gastric fluid of pH less than 2.0. Aspiration through a gastrict tube did not empty the stomach completely and the volume thus obtained gave a falsely low estimate of the gastric volume."}
{"id": "PMID:23892", "title": "Histopathology of veins after intravenous lorazepam and RO 21-3981.", "content": "A previously established rat model has been utilized to demonstrate that an acute inflammatory response occurs after high intravenous doses of lorazepam. This occurs only with high concentrations of drug equivalent to 20 times the normal clinical dosage in man. In contract, water soluble RO 21-3981 produces no vascular pathology in any dosage evaluated. It appears that propylene glycol may play a role in the pathogenesis of the intravascular injury observed.", "contents": "Histopathology of veins after intravenous lorazepam and RO 21-3981. A previously established rat model has been utilized to demonstrate that an acute inflammatory response occurs after high intravenous doses of lorazepam. This occurs only with high concentrations of drug equivalent to 20 times the normal clinical dosage in man. In contract, water soluble RO 21-3981 produces no vascular pathology in any dosage evaluated. It appears that propylene glycol may play a role in the pathogenesis of the intravascular injury observed."}
{"id": "PMID:23894", "title": "Detection and prevalence of pneumococci with increased resistance to penicillin.", "content": "Susceptibility to penicillin was determined for 6000 strains of pneumococci isolated during 1974--76 from patients in Alberta and the adjacent region of the Northwest Territories. Strains were considered to be relatively resistant if the minimum inhibitory concentration (MIC) of penicillin was 0.16 microgram (0.26 U)/mL or more, which is eight or more times greater than the MIC for fully susceptible strains. Resistance was detected in 143 strains (2.4%) isolated from 122 patients and belonging to four capsular types. The MIC of the most resistant strains was 0.32 microgram (0.53 U/mL. Penicillin-resistant strains were highly resistant to oxacillin, the MIC being at least 30 times greater than that for penicillin-susceptible strains. Pneumococci resistant to penicillin may readily be detected by the narrowness or absence of a zone of inhibition around a 1-microgram oxacillin disc in susceptibility tests on blood agar. The degree of resistance reported here is relative and does not necessarily preclude successful treatment with full therapeutic doses of penicillin G, but penicillin preparations that give low blood concentrations may not be suitable for treating infections caused by these strains.", "contents": "Detection and prevalence of pneumococci with increased resistance to penicillin. Susceptibility to penicillin was determined for 6000 strains of pneumococci isolated during 1974--76 from patients in Alberta and the adjacent region of the Northwest Territories. Strains were considered to be relatively resistant if the minimum inhibitory concentration (MIC) of penicillin was 0.16 microgram (0.26 U)/mL or more, which is eight or more times greater than the MIC for fully susceptible strains. Resistance was detected in 143 strains (2.4%) isolated from 122 patients and belonging to four capsular types. The MIC of the most resistant strains was 0.32 microgram (0.53 U/mL. Penicillin-resistant strains were highly resistant to oxacillin, the MIC being at least 30 times greater than that for penicillin-susceptible strains. Pneumococci resistant to penicillin may readily be detected by the narrowness or absence of a zone of inhibition around a 1-microgram oxacillin disc in susceptibility tests on blood agar. The degree of resistance reported here is relative and does not necessarily preclude successful treatment with full therapeutic doses of penicillin G, but penicillin preparations that give low blood concentrations may not be suitable for treating infections caused by these strains."}
{"id": "PMID:23897", "title": "Gamma-glutamyltransferase in putative premalignant liver cell populations during hepatocarcinogenesis.", "content": "The activity of gamma-glutamyltransferase, as measured quantitatively and by histochemical staining, was studied in different cell populations during the induction of liver cancer with 2-acetylaminofluorene (2-AAF) or diethylnitrosamine and compared with findings in fetal and in intact and regenerating adult liver. The enzyme activity is 20-fold higher in 12-week nodules than in control livers and 30-fold higher in 20-week nodules than in controls. A similar 30-fold increase in activity relative to control is present in hepatomas, induced by either 2-AAF or diethylnitrosamine, and in fetal hepatocytes. The enzyme shows increases in activity in foci of very early putative preneoplastic hepatocytes induced by a single dose of diethylnitrosamine and selected by low doses of 2-AAF plus partial hepatectomy. By 7 days, the foci show a 4-fold increase in enzyme activity, and by 3 weeks they are 40-fold higher than in the control liver. Histochemically, the foci are strongly positive for gamma-glutamyltransferase, especially in the bile canaliculi. By 21 days, the ductular (oval) cells induced by 2-AAF have disappeared. When stained for the enzyme activity, the foci stand out clearly against the negative background of the liver, allowing easy quantitation. It appears that gamma-glutamyltransferase is a useful marker for preneoplastic hepatocytes.", "contents": "Gamma-glutamyltransferase in putative premalignant liver cell populations during hepatocarcinogenesis. The activity of gamma-glutamyltransferase, as measured quantitatively and by histochemical staining, was studied in different cell populations during the induction of liver cancer with 2-acetylaminofluorene (2-AAF) or diethylnitrosamine and compared with findings in fetal and in intact and regenerating adult liver. The enzyme activity is 20-fold higher in 12-week nodules than in control livers and 30-fold higher in 20-week nodules than in controls. A similar 30-fold increase in activity relative to control is present in hepatomas, induced by either 2-AAF or diethylnitrosamine, and in fetal hepatocytes. The enzyme shows increases in activity in foci of very early putative preneoplastic hepatocytes induced by a single dose of diethylnitrosamine and selected by low doses of 2-AAF plus partial hepatectomy. By 7 days, the foci show a 4-fold increase in enzyme activity, and by 3 weeks they are 40-fold higher than in the control liver. Histochemically, the foci are strongly positive for gamma-glutamyltransferase, especially in the bile canaliculi. By 21 days, the ductular (oval) cells induced by 2-AAF have disappeared. When stained for the enzyme activity, the foci stand out clearly against the negative background of the liver, allowing easy quantitation. It appears that gamma-glutamyltransferase is a useful marker for preneoplastic hepatocytes."}
{"id": "PMID:23898", "title": "Psychotropic drugs as potential antitumor agents: a selective screening study.", "content": "Compounds with known psychotropic properties were tested for activity in murine ip L1210 leukemia and B 16 melanoma in a protocol designed to obtain leads for new antitumor agents which might also possess central nervous system (CNS) antitumor properties. Barbiturates and hallucinogenic compounds were the only compound types deliberately excluded. Representatives from most of the other known CNS agent classes were included among the 297 psychotropic drugs evaluated. Sixteen of these agents were reproducibly active against the L1210 tumor system with T/C values of 125%. Phenothiazines such as fluphenazine and butyrophenones such as triperidol were prominent among the confirmed active structural types. Dopamine, a beta-phenethylamine neurotrasmitter, was active. While reproducible B16 melanoma activity was not observed among the psychotropic drugs, most of the L1210 confirmed active agents were effective against the ip P388 tumor model and also were active in vitro against KB cells. Ic L1210 activity was not observed among the few compounds chosen for testing in that tumor system. The yield of ip L1210 confirmed actives from this group of psychotropic agents was 18 times that which would have been expected from the random screening of compounds.", "contents": "Psychotropic drugs as potential antitumor agents: a selective screening study. Compounds with known psychotropic properties were tested for activity in murine ip L1210 leukemia and B 16 melanoma in a protocol designed to obtain leads for new antitumor agents which might also possess central nervous system (CNS) antitumor properties. Barbiturates and hallucinogenic compounds were the only compound types deliberately excluded. Representatives from most of the other known CNS agent classes were included among the 297 psychotropic drugs evaluated. Sixteen of these agents were reproducibly active against the L1210 tumor system with T/C values of 125%. Phenothiazines such as fluphenazine and butyrophenones such as triperidol were prominent among the confirmed active structural types. Dopamine, a beta-phenethylamine neurotrasmitter, was active. While reproducible B16 melanoma activity was not observed among the psychotropic drugs, most of the L1210 confirmed active agents were effective against the ip P388 tumor model and also were active in vitro against KB cells. Ic L1210 activity was not observed among the few compounds chosen for testing in that tumor system. The yield of ip L1210 confirmed actives from this group of psychotropic agents was 18 times that which would have been expected from the random screening of compounds."}
{"id": "PMID:23899", "title": "Lack of effect of hypercapnic acidosis on elasticity of cat papillary muscles.", "content": "Chages in external pH from 7.40 to 6.95 obtained by changing the pCO2 of the medium at constant bicarbonate concentration produced in cat papillary muscles a significant decrease in isometric tension with no changes in time to peak tension. Active and resting stiffness, as determined by two different methods, did not change under conditions of hypercapnic acidosis.", "contents": "Lack of effect of hypercapnic acidosis on elasticity of cat papillary muscles. Chages in external pH from 7.40 to 6.95 obtained by changing the pCO2 of the medium at constant bicarbonate concentration produced in cat papillary muscles a significant decrease in isometric tension with no changes in time to peak tension. Active and resting stiffness, as determined by two different methods, did not change under conditions of hypercapnic acidosis."}
{"id": "PMID:23901", "title": "Species-specific aggregation factor in sponges. VII. Its effect on cyclic amp and cyclic gmp metabolism in cells of Geodia cydonium.", "content": "In dissociated single cells from the sponge Geodia cydonium, DNA synthesis is initiated after incubation with a homologous, soluble aggregation factor. During the DNA-initiation phase the cyclic AMP- and cyclic GMP levels vary drastically; the cyclic AMP content drops from 2.2 pmol/10(6) cells to 0.3 pmol/10(6) cells while the cyclic GMP content increases from 0.6 pmol to 3.7 pmol/10(6) cells. The activity of neither the adenylate cyclase nor of the guanylate cyclase isolated from cells which have been incubated for different periods of time with the aggregation factor, is changed. The soluble as well as the particulate enzyme activities were checked in vitro. The cyclic nucleotide receptors have been isolated from the sponge cells and characterized with respect to their molecular weight, dissociation constant for cyclic AMP or cyclic GMP and intracellular concentration. None of these parameters are altered during aggregation factor-mediated DNA initiation. From these data it is concluded that the regulation of cyclic nucleotide levels is a consequence of a changed activity of nucleotide cyclases or of phosphodiesterases, but this is presumably not caused by a changed rate of synthesis of nucleotide cyclases or of cyclic nucleotide receptors.", "contents": "Species-specific aggregation factor in sponges. VII. Its effect on cyclic amp and cyclic gmp metabolism in cells of Geodia cydonium. In dissociated single cells from the sponge Geodia cydonium, DNA synthesis is initiated after incubation with a homologous, soluble aggregation factor. During the DNA-initiation phase the cyclic AMP- and cyclic GMP levels vary drastically; the cyclic AMP content drops from 2.2 pmol/10(6) cells to 0.3 pmol/10(6) cells while the cyclic GMP content increases from 0.6 pmol to 3.7 pmol/10(6) cells. The activity of neither the adenylate cyclase nor of the guanylate cyclase isolated from cells which have been incubated for different periods of time with the aggregation factor, is changed. The soluble as well as the particulate enzyme activities were checked in vitro. The cyclic nucleotide receptors have been isolated from the sponge cells and characterized with respect to their molecular weight, dissociation constant for cyclic AMP or cyclic GMP and intracellular concentration. None of these parameters are altered during aggregation factor-mediated DNA initiation. From these data it is concluded that the regulation of cyclic nucleotide levels is a consequence of a changed activity of nucleotide cyclases or of phosphodiesterases, but this is presumably not caused by a changed rate of synthesis of nucleotide cyclases or of cyclic nucleotide receptors."}
{"id": "PMID:23902", "title": "Enteroendocrine cells in the digestive tract of Barbus conchonius (teleostei, cyprinidae).", "content": "Just as in other cyprinids, three zones can be distinguished in the digestive tract of Barbus conchonius. A fat absorptive zone (65--75%), including the intestinal bulb, is followed by a protein absorptive zone (25--35%) and a small ion and water absorptive zone (less than 5%). The main characteristics of these zones are described. Four types of enteroendocrine cells can be distinguished between the intestinal epithelial cells. The number decreases in the caudal direction, and there are very few in the protein absorptive zone. All the enteroendocrine cells are argyrophilic and differ mainly in the size and shape of their secretory granules. Serotonin producing and hence argentaffin cells have not been found. Amine precursor uptake and decarboxylation (APUD) by the enteroendocrine cells of adult fishes has not been observed. The possible functions of the enteroendocrine cells are discussed. (Auto-)phagosomes, common in epithelial cells of the gut of B. conchonius, show similar staining characteristics as the enteroendocrine cells; their function is discussed.", "contents": "Enteroendocrine cells in the digestive tract of Barbus conchonius (teleostei, cyprinidae). Just as in other cyprinids, three zones can be distinguished in the digestive tract of Barbus conchonius. A fat absorptive zone (65--75%), including the intestinal bulb, is followed by a protein absorptive zone (25--35%) and a small ion and water absorptive zone (less than 5%). The main characteristics of these zones are described. Four types of enteroendocrine cells can be distinguished between the intestinal epithelial cells. The number decreases in the caudal direction, and there are very few in the protein absorptive zone. All the enteroendocrine cells are argyrophilic and differ mainly in the size and shape of their secretory granules. Serotonin producing and hence argentaffin cells have not been found. Amine precursor uptake and decarboxylation (APUD) by the enteroendocrine cells of adult fishes has not been observed. The possible functions of the enteroendocrine cells are discussed. (Auto-)phagosomes, common in epithelial cells of the gut of B. conchonius, show similar staining characteristics as the enteroendocrine cells; their function is discussed."}
{"id": "PMID:23903", "title": "Ultrastructural appearance of neurosecretory granules in the sinus gland of the crab after different fixation procedures.", "content": "The appearance of neurosecretory granules in the crab sinus gland was studied after fixation at different pHs. Whereas at pH 7.0 the neurosecretory granules were pleomorphic with respect to electron density, at pH 5.0 or 6.0 all the granules remained electron dense. The possible role of maturation as an explanation of this observation is discussed.", "contents": "Ultrastructural appearance of neurosecretory granules in the sinus gland of the crab after different fixation procedures. The appearance of neurosecretory granules in the crab sinus gland was studied after fixation at different pHs. Whereas at pH 7.0 the neurosecretory granules were pleomorphic with respect to electron density, at pH 5.0 or 6.0 all the granules remained electron dense. The possible role of maturation as an explanation of this observation is discussed."}
{"id": "PMID:23904", "title": "A radioautographic study of the neuroepithelial bodies of the lungs in fetal and neonatal rabbits.", "content": "The neuroepithelial bodies (NEB's) of the lung of 29-day-old fetuses and 1-day-old rabbits, under the conditions of this study, neither take up 3H-thymidine nor undergo mitosis. Also the NEB's are not derived at these times from proliferations of other kinds of epithelial cells in the intrapulmonary airways. It is, therefore, suggested that the difference in numbers of NEB's previously observed by us, between the 29-day fetus and the 1-day-old rabbit, is due either to regranulation or acquisition of argyrophilic material by the NEB's or differentiation of other epithelial types. It is concluded that the NEB's are composed of well differentiated cells, which have a greatly reduced capacity to undergo mitosis.", "contents": "A radioautographic study of the neuroepithelial bodies of the lungs in fetal and neonatal rabbits. The neuroepithelial bodies (NEB's) of the lung of 29-day-old fetuses and 1-day-old rabbits, under the conditions of this study, neither take up 3H-thymidine nor undergo mitosis. Also the NEB's are not derived at these times from proliferations of other kinds of epithelial cells in the intrapulmonary airways. It is, therefore, suggested that the difference in numbers of NEB's previously observed by us, between the 29-day fetus and the 1-day-old rabbit, is due either to regranulation or acquisition of argyrophilic material by the NEB's or differentiation of other epithelial types. It is concluded that the NEB's are composed of well differentiated cells, which have a greatly reduced capacity to undergo mitosis."}
{"id": "PMID:23909", "title": "P-Nitrophenol-alpha-D-glucopyranoside as substrate for measurement of maltase activity in human semen.", "content": "Hitherto, seminal plasma maltase has been measured with maltose as substrate; this method is time consuming and lacks specificity. The use of a synthetic substrate, p-nitrophenol-alpha-D-glucopyranoside, allows accurate and rapid determination of this activity. When maltase is added to the incubation medium (the substrate and reduced glutathione in potassium phosphate buffer, pH 6.8), maintained at 37 degrees C, hydrolysis of the original substrate to p-nitrophenol goes at a constant rate during 4 h. Under optimal conditions of incubation, the Michaelis constant of the reaction, calculated by the Hanes method, was 2.92 +/- 0.84 (SD) X 10(-3) for six different semen samples. Isomaltase appeared to be absent from seminal plasma. The enzyme is stable to freezing and slow thawing and can be stored for at least 26 days at -80 degrees C. Its molecular weight is 259 000. Tris(hydroxymethyl)aminomethane (pH 6.8) exerts a noncompetitive inhibition on the enzyme activity. In 68 men 23 to 45 years old, whose semen analyses were normal, the seminal plasma maltase activity was 467 +/- 135 (SD) mU/g of protein. It was generally decreased in patients with infertility disorders.", "contents": "P-Nitrophenol-alpha-D-glucopyranoside as substrate for measurement of maltase activity in human semen. Hitherto, seminal plasma maltase has been measured with maltose as substrate; this method is time consuming and lacks specificity. The use of a synthetic substrate, p-nitrophenol-alpha-D-glucopyranoside, allows accurate and rapid determination of this activity. When maltase is added to the incubation medium (the substrate and reduced glutathione in potassium phosphate buffer, pH 6.8), maintained at 37 degrees C, hydrolysis of the original substrate to p-nitrophenol goes at a constant rate during 4 h. Under optimal conditions of incubation, the Michaelis constant of the reaction, calculated by the Hanes method, was 2.92 +/- 0.84 (SD) X 10(-3) for six different semen samples. Isomaltase appeared to be absent from seminal plasma. The enzyme is stable to freezing and slow thawing and can be stored for at least 26 days at -80 degrees C. Its molecular weight is 259 000. Tris(hydroxymethyl)aminomethane (pH 6.8) exerts a noncompetitive inhibition on the enzyme activity. In 68 men 23 to 45 years old, whose semen analyses were normal, the seminal plasma maltase activity was 467 +/- 135 (SD) mU/g of protein. It was generally decreased in patients with infertility disorders."}
{"id": "PMID:23910", "title": "Optimal reaction conditions for assaying human lactate dehydrogenase pyruvate-to-lactate at 25, 30, and 37 degrees C.", "content": "Optimal reaction conditions for assaying human lactate dehydrogenase pyruvate-to-lactate were determined for isoenzymes 1 and 5 at 25, 30, and 37 degrees C. Three of the nine different buffers examined--imidazole, triethanolamine, and N-tris(hydroxymethyl)-methyl-2-aminoethane sulfonic acid--are satisfactory. Beta-NADH, pyruvate, and hydrogen ion concentrations were chosen to measure both isoenzymes with maximal-equal-sustainable efficiency at the lowest substrate concentrations. Approximately 95% of each isoenzyme is measured, for activities up to threefold the upper normal limit, if the measurements are made immediately after the reaction is initiated. The Arrhenius relationship for each isoenzyme is unique. Interconversion of results from one temperature to another is practical only with reservations. Results at 37 degrees C are not as reliable as those at 25 degrees C.", "contents": "Optimal reaction conditions for assaying human lactate dehydrogenase pyruvate-to-lactate at 25, 30, and 37 degrees C. Optimal reaction conditions for assaying human lactate dehydrogenase pyruvate-to-lactate were determined for isoenzymes 1 and 5 at 25, 30, and 37 degrees C. Three of the nine different buffers examined--imidazole, triethanolamine, and N-tris(hydroxymethyl)-methyl-2-aminoethane sulfonic acid--are satisfactory. Beta-NADH, pyruvate, and hydrogen ion concentrations were chosen to measure both isoenzymes with maximal-equal-sustainable efficiency at the lowest substrate concentrations. Approximately 95% of each isoenzyme is measured, for activities up to threefold the upper normal limit, if the measurements are made immediately after the reaction is initiated. The Arrhenius relationship for each isoenzyme is unique. Interconversion of results from one temperature to another is practical only with reservations. Results at 37 degrees C are not as reliable as those at 25 degrees C."}
{"id": "PMID:23911", "title": "D(-)-N-Methylglucamine buffer for pH 8.5 to 10.5.", "content": "A new amine buffer for the pH range 8.5 to 10.5 based on D(-)-N-methylglucamine and its hydrochloride is described. Important physical and chemical constants characterizing this buffer system have been determined: thermodynamic pKa = 9.52 (25 degrees C), buffer capacity = 0.055, dilution value pH 1/2 = -0.02, temperature coefficient dpKa/dT = 0.023, the heat of ionization delta H degrees = 36.93 kj mol-1. D(-)-N-Methylglucamine, which is available in highly purified form, is highly soluble in water. Thus one can prepare either buffer solutions or stable solid mixtures when combined with D(-)-N-methylglucaminium chloride. D(-)-N-Methylglucamine buffers are suitable for both biochemistry and pH control.", "contents": "D(-)-N-Methylglucamine buffer for pH 8.5 to 10.5. A new amine buffer for the pH range 8.5 to 10.5 based on D(-)-N-methylglucamine and its hydrochloride is described. Important physical and chemical constants characterizing this buffer system have been determined: thermodynamic pKa = 9.52 (25 degrees C), buffer capacity = 0.055, dilution value pH 1/2 = -0.02, temperature coefficient dpKa/dT = 0.023, the heat of ionization delta H degrees = 36.93 kj mol-1. D(-)-N-Methylglucamine, which is available in highly purified form, is highly soluble in water. Thus one can prepare either buffer solutions or stable solid mixtures when combined with D(-)-N-methylglucaminium chloride. D(-)-N-Methylglucamine buffers are suitable for both biochemistry and pH control."}
{"id": "PMID:23912", "title": "Synthetic substrate beta-glucosidase activity in leukocytes: a reproducible method for the identification of patients and carriers of Gaucher's disease.", "content": "A method is described for the identification of patients and carriers of Gaucher's disease, using leukocytes from a small volume of blood. The fluorogenic substrate, 4-methylumbelliferyl-beta-D-glucopyranoside, was assayed in the presence of pure sodium taurocholate (2.5 mg/ml) and Triton X-100 (2.0 mg/ml). Some commercial brands of pure sodium taurocholate were satisfactory for this purpose. The pH optimum for controls, Gaucher disease carriers and Gaucher disease patients was 5.4 using citrate-phosphate buffer. Although leukocytes prepared from only a small amount of blood (2-8 ml) are required, there is sufficient quantity for measuring other lysosomal enzymes as controls. Using this method, 12 patients with all types of Gaucher's disease and 12 obligate heterozygotes were identified. Carrier status was predicted in six other family members and ruled out in six others. Eight unaffected people married to Gaucher carriers or Gaucher patients were predicted to be non-carriers of Gaucher's disease, thereby ruling out children affected with Gaucher's disease in that mating.", "contents": "Synthetic substrate beta-glucosidase activity in leukocytes: a reproducible method for the identification of patients and carriers of Gaucher's disease. A method is described for the identification of patients and carriers of Gaucher's disease, using leukocytes from a small volume of blood. The fluorogenic substrate, 4-methylumbelliferyl-beta-D-glucopyranoside, was assayed in the presence of pure sodium taurocholate (2.5 mg/ml) and Triton X-100 (2.0 mg/ml). Some commercial brands of pure sodium taurocholate were satisfactory for this purpose. The pH optimum for controls, Gaucher disease carriers and Gaucher disease patients was 5.4 using citrate-phosphate buffer. Although leukocytes prepared from only a small amount of blood (2-8 ml) are required, there is sufficient quantity for measuring other lysosomal enzymes as controls. Using this method, 12 patients with all types of Gaucher's disease and 12 obligate heterozygotes were identified. Carrier status was predicted in six other family members and ruled out in six others. Eight unaffected people married to Gaucher carriers or Gaucher patients were predicted to be non-carriers of Gaucher's disease, thereby ruling out children affected with Gaucher's disease in that mating."}
{"id": "PMID:23913", "title": "Cystic fibrosis liver sialyltransferase.", "content": "The activity of sialytransferase with regard to the glycoprotein substrates asialofetuin and asialo-ovine submaxillary mucin was determined in normal, pathological control, and cystic fibrosis liver homogenates. Cystic fibrosis and pathological livers have about 40% of the average normal specific activity for sialytransferase. Several properties of cystic fibrosis sialytransferase were investigated and compared to those of the normal liver enzyme (Alhadeff et al. 1977). The pH optima curves were similar, but cystic fibrosis sialyltransferase appears to be more thermolabile than the normal liver enzyme. Isoelectric focusing studies revealed that the three most basic forms of sialyltransferase which are found in normal livers are deficient or absent in most cystic fibrosis liver. The data suggest that altered glycoprotein-sialyltransferases may be present in cystic fibrosis livers, probably a secondary effect due to general liver pathology.", "contents": "Cystic fibrosis liver sialyltransferase. The activity of sialytransferase with regard to the glycoprotein substrates asialofetuin and asialo-ovine submaxillary mucin was determined in normal, pathological control, and cystic fibrosis liver homogenates. Cystic fibrosis and pathological livers have about 40% of the average normal specific activity for sialytransferase. Several properties of cystic fibrosis sialytransferase were investigated and compared to those of the normal liver enzyme (Alhadeff et al. 1977). The pH optima curves were similar, but cystic fibrosis sialyltransferase appears to be more thermolabile than the normal liver enzyme. Isoelectric focusing studies revealed that the three most basic forms of sialyltransferase which are found in normal livers are deficient or absent in most cystic fibrosis liver. The data suggest that altered glycoprotein-sialyltransferases may be present in cystic fibrosis livers, probably a secondary effect due to general liver pathology."}
{"id": "PMID:23936", "title": "[Standardisation of obtaining blood samples: influence of tourniquet application on 33 constituents of blood and serum (author's transl)].", "content": "The extent and dynamics of changes by short (1 min) or prolonged (6 min) tourniquet application while obtaining venous blood samples were analysed with respect ot 33 frequently measured constituents of blood and serum. After 6-minute tourniquet application the values for red cells, haemoglobin, packed cell volume, total protein, albumen, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, creatinekinase, bilirubin, cholesterol, total glycerol and calcium increased by an average of 4-9%. One-minute tourniquet application did not have a significant effect. Levels of sodium, potassium, carbon dioxide, creatinine, uric acid, ratio of electrophoretic fractions and the MCV, MCH and MCHC indices were not affected even by 6-minute tourniquet applications. The introduction of blood sampling under standardised conditions is proposed.", "contents": "[Standardisation of obtaining blood samples: influence of tourniquet application on 33 constituents of blood and serum (author's transl)]. The extent and dynamics of changes by short (1 min) or prolonged (6 min) tourniquet application while obtaining venous blood samples were analysed with respect ot 33 frequently measured constituents of blood and serum. After 6-minute tourniquet application the values for red cells, haemoglobin, packed cell volume, total protein, albumen, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, creatinekinase, bilirubin, cholesterol, total glycerol and calcium increased by an average of 4-9%. One-minute tourniquet application did not have a significant effect. Levels of sodium, potassium, carbon dioxide, creatinine, uric acid, ratio of electrophoretic fractions and the MCV, MCH and MCHC indices were not affected even by 6-minute tourniquet applications. The introduction of blood sampling under standardised conditions is proposed."}
{"id": "PMID:23937", "title": "Drugs and depression.", "content": "Moderate or severe depression is now one of the most common diseases of our time with a prevalence of nearly 3%. It seems likely that this prevalence has increased as a result of the wider use of drugs which have an effect on the neurotransmitters. Changes in the levels of these neurotransmitters in the central nervous system are thought to be the biochemical basis for the development of at least some depressive illnesses. Drug-induced depressions are more likely to occur in those individuals who are genetically predisposed to depression or who have had a previous depressive illness. Other groups who are particularly susceptible to these effects are the elderly. Many groups of drugs have a primary or secondary action on the central nervous system neurotransmitter function. Some 200 drugs have been claimed to cause depression in certain patients, but only a relatively small number precipitate depressive symptoms with any frequency. Those most commonly implicated are the long-acting antipsychotics, barbiturates, ethanol, oral contraceptives and antihypertensive agents. It is important to remember that some drugs, such as reserpine, cause depression as a side-effect during their therapeutic use whereas others, such as fenfluramine, cause depression mainly when they are withdrawn too rapidly. In those patients presenting with depression, it is important to review the current drug therapy in order to assess the part played by these drugs in the development of the depression. Following this assessment, drug therapy should be adjusted appropriately. However, a distinction must be made between the symptoms of depression, those physiological changes which occur during treatment with a variety of drugs, and the patient's reaction to the disease for which they are being treated.", "contents": "Drugs and depression. Moderate or severe depression is now one of the most common diseases of our time with a prevalence of nearly 3%. It seems likely that this prevalence has increased as a result of the wider use of drugs which have an effect on the neurotransmitters. Changes in the levels of these neurotransmitters in the central nervous system are thought to be the biochemical basis for the development of at least some depressive illnesses. Drug-induced depressions are more likely to occur in those individuals who are genetically predisposed to depression or who have had a previous depressive illness. Other groups who are particularly susceptible to these effects are the elderly. Many groups of drugs have a primary or secondary action on the central nervous system neurotransmitter function. Some 200 drugs have been claimed to cause depression in certain patients, but only a relatively small number precipitate depressive symptoms with any frequency. Those most commonly implicated are the long-acting antipsychotics, barbiturates, ethanol, oral contraceptives and antihypertensive agents. It is important to remember that some drugs, such as reserpine, cause depression as a side-effect during their therapeutic use whereas others, such as fenfluramine, cause depression mainly when they are withdrawn too rapidly. In those patients presenting with depression, it is important to review the current drug therapy in order to assess the part played by these drugs in the development of the depression. Following this assessment, drug therapy should be adjusted appropriately. However, a distinction must be made between the symptoms of depression, those physiological changes which occur during treatment with a variety of drugs, and the patient's reaction to the disease for which they are being treated."}
{"id": "PMID:23938", "title": "Drug interactions with antihypertensive drugs.", "content": "Drug interactions with antihypertensive drugs can be either beneficial or hazardous. The hazardous interactions are relatively infrequent but must be shown so they can be avoided. Those of most importance involve interaction with guanethidine-type agents and tricyclic antidepressants, amphetamine-type anorexiants or phenolpropanolamine-type common cold remedies; combined use of potassium retaining diuretics with potassium supplements; and incautious use of diuretics with cardiac glycosides. The beneficial interactions are the basis for modern antihypertensive therapy and can be of major help if logically applied to therapeutic problems.", "contents": "Drug interactions with antihypertensive drugs. Drug interactions with antihypertensive drugs can be either beneficial or hazardous. The hazardous interactions are relatively infrequent but must be shown so they can be avoided. Those of most importance involve interaction with guanethidine-type agents and tricyclic antidepressants, amphetamine-type anorexiants or phenolpropanolamine-type common cold remedies; combined use of potassium retaining diuretics with potassium supplements; and incautious use of diuretics with cardiac glycosides. The beneficial interactions are the basis for modern antihypertensive therapy and can be of major help if logically applied to therapeutic problems."}
{"id": "PMID:23941", "title": "The molluscicidal properties of natural products from Ambrosia maritima.", "content": "The molluscicidal properties of Damsin \"I\", Ambrosin \"II\", and tribromodamsin \"III\" were investigated against the intermediate hosts of schistosomiasis Biomphalaria alexandrina and Bulinus truncatus. Although Damsin was to some extent more toxic against B. alexandrina than the other two compounds, it was less toxic than them against B. truncatus after 24 hr exposure periods. There is a flex relationship between concentration of Damsin and exposure period to prodce 100% mortality. The molluscicidal potency of Damsin remained stable over a wide range of pH values, but was affected by storage, sunlight and river bed-mud. Structure-activity relationship is included.", "contents": "The molluscicidal properties of natural products from Ambrosia maritima. The molluscicidal properties of Damsin \"I\", Ambrosin \"II\", and tribromodamsin \"III\" were investigated against the intermediate hosts of schistosomiasis Biomphalaria alexandrina and Bulinus truncatus. Although Damsin was to some extent more toxic against B. alexandrina than the other two compounds, it was less toxic than them against B. truncatus after 24 hr exposure periods. There is a flex relationship between concentration of Damsin and exposure period to prodce 100% mortality. The molluscicidal potency of Damsin remained stable over a wide range of pH values, but was affected by storage, sunlight and river bed-mud. Structure-activity relationship is included."}
{"id": "PMID:23942", "title": "Arylsulfatases in bilharziasis.", "content": "Arylsulfatase A and B in urine have been estimated in 18 normal subjects and 50 bilharziasis patients. The bilharziasis patients were divided into two groups according to the type of infeciton. Those with bilharziasis haematobian type of infection and those with the bilharziasis mansoni type. Each group was further subdivided into subgroups according to the severity and progress of the disease. The activities of arylsulfatase A and B were significantly elevated in all the groups of patients studied and it is evident that there is a progressive increase with the progress of the disease in both types of bilharziasis infections (the haematobian and mansoni types). Liver dysfunction consequent of bilharzial infestation appears to take part in the mechanism of induction of the bilharzial bladder cancer.", "contents": "Arylsulfatases in bilharziasis. Arylsulfatase A and B in urine have been estimated in 18 normal subjects and 50 bilharziasis patients. The bilharziasis patients were divided into two groups according to the type of infeciton. Those with bilharziasis haematobian type of infection and those with the bilharziasis mansoni type. Each group was further subdivided into subgroups according to the severity and progress of the disease. The activities of arylsulfatase A and B were significantly elevated in all the groups of patients studied and it is evident that there is a progressive increase with the progress of the disease in both types of bilharziasis infections (the haematobian and mansoni types). Liver dysfunction consequent of bilharzial infestation appears to take part in the mechanism of induction of the bilharzial bladder cancer."}
{"id": "PMID:23943", "title": "Laboratory model ecosystem evaluation of the chemical and biological behavior of radiolabeled micropollutants.", "content": "A standardized laboratory model ecosystem has been used to evaluate the comparative behavior of radiolabeled micropollutants including organochlorine, organophosphorus, carbamate, and hormone-mimic insecticides; herbicides; important industrial organic compounds including phthalate esters and PCB's; and specific pollutants such as TCBD and hexachlorobenzene. The compounds have been studies for ecological effects over a terrestrial-aquatic interface and through several food chains, especially with regard to the development of quantitative information on ecological magnification and biodegradability index. The pathways of chemical degradation in the various organisms have been evaluated and the ecological effects of degradation products investigated. Illustrations are given of the use of the model ecosystem technology for screening new candidate pesticides for effects on environmental quality; for evaluating the hazards of environmental pollution by industrial waste effluents; and for fundamental studies of the principles fo biodegradability of organic chemicals in a variety of organisms.", "contents": "Laboratory model ecosystem evaluation of the chemical and biological behavior of radiolabeled micropollutants. A standardized laboratory model ecosystem has been used to evaluate the comparative behavior of radiolabeled micropollutants including organochlorine, organophosphorus, carbamate, and hormone-mimic insecticides; herbicides; important industrial organic compounds including phthalate esters and PCB's; and specific pollutants such as TCBD and hexachlorobenzene. The compounds have been studies for ecological effects over a terrestrial-aquatic interface and through several food chains, especially with regard to the development of quantitative information on ecological magnification and biodegradability index. The pathways of chemical degradation in the various organisms have been evaluated and the ecological effects of degradation products investigated. Illustrations are given of the use of the model ecosystem technology for screening new candidate pesticides for effects on environmental quality; for evaluating the hazards of environmental pollution by industrial waste effluents; and for fundamental studies of the principles fo biodegradability of organic chemicals in a variety of organisms."}
{"id": "PMID:23944", "title": "Influence of denervation and reinnervation on autolytic activity and on protein composition of skeletal muscle in rat.", "content": "Changes in the proteolytic activity and in the relative content of protein in soluble, myofibrillar and insoluble fractions were investigated following denervation and reinnervation of the soleus and tibialis anterior muscles of the rat. After denervation an increase of autolysis in the acid and neutral pH range, but not in the alkaline one, was found in both muscles. An increased autolysis at the acid and neutral pH range was also observed in both muscles after reinnervation, when the weight of the muscles increased. The results indicate the lack of inverse relationship between the changes of proteolytic activity and the decrease or increase of the amount of muscle protein in the course of muscle atrophy and regeneration.", "contents": "Influence of denervation and reinnervation on autolytic activity and on protein composition of skeletal muscle in rat. Changes in the proteolytic activity and in the relative content of protein in soluble, myofibrillar and insoluble fractions were investigated following denervation and reinnervation of the soleus and tibialis anterior muscles of the rat. After denervation an increase of autolysis in the acid and neutral pH range, but not in the alkaline one, was found in both muscles. An increased autolysis at the acid and neutral pH range was also observed in both muscles after reinnervation, when the weight of the muscles increased. The results indicate the lack of inverse relationship between the changes of proteolytic activity and the decrease or increase of the amount of muscle protein in the course of muscle atrophy and regeneration."}
{"id": "PMID:23945", "title": "Glucokinase and hexokinase in pig erythrocytes.", "content": "We have shown different enzymatic activities responsible for the phosphorylation of glucose in pig erythrocytes. These activities were observed after partial purification from hemolyzed red cells. One of the enzymes involved is the hexokinase which is present in all tissues; the other is similar to hepatic glucokinase. We have determined the kinetic properties of these activities in hemolysates and in partially purified preparations. Their electrophoretic-migration characteristics were studied too.", "contents": "Glucokinase and hexokinase in pig erythrocytes. We have shown different enzymatic activities responsible for the phosphorylation of glucose in pig erythrocytes. These activities were observed after partial purification from hemolyzed red cells. One of the enzymes involved is the hexokinase which is present in all tissues; the other is similar to hepatic glucokinase. We have determined the kinetic properties of these activities in hemolysates and in partially purified preparations. Their electrophoretic-migration characteristics were studied too."}
{"id": "PMID:23947", "title": "Electrostatic interactions at charged lipid membranes. Measurement of surface pH with fluorescent lipoid pH indicators.", "content": "The 5-dimethylaminonapthalene-1-sulfonyl (dansyl) chromophore attached to the polar head groups of lipids has been used as a fluorescent lipoid pH indicator to evaluate the interfacial pH in lipid-water lamellar systems prepared from negatively charged lipids. The pH in the vicinity of the charged lipid bilayers is different from the pH of the bulk aqueous phase and the difference is a function of the electrolyte concentration in the aqueous phase and of the lipid packing in the bilayer. At a fixed electrolyte concentration in the aqueous phase, the observed interfacial pH is 0.6 to 0.7 pH units lower above the thermal phase transition of the lipid than it is below this temperature. A quantitative interpretation of the results is given on the basis of the Gouy-Chapman theory. The results indicate that the dansyl chromophore is located in front of the charged surface and its distance from this surface increases with a decrease in lipid packing.", "contents": "Electrostatic interactions at charged lipid membranes. Measurement of surface pH with fluorescent lipoid pH indicators. The 5-dimethylaminonapthalene-1-sulfonyl (dansyl) chromophore attached to the polar head groups of lipids has been used as a fluorescent lipoid pH indicator to evaluate the interfacial pH in lipid-water lamellar systems prepared from negatively charged lipids. The pH in the vicinity of the charged lipid bilayers is different from the pH of the bulk aqueous phase and the difference is a function of the electrolyte concentration in the aqueous phase and of the lipid packing in the bilayer. At a fixed electrolyte concentration in the aqueous phase, the observed interfacial pH is 0.6 to 0.7 pH units lower above the thermal phase transition of the lipid than it is below this temperature. A quantitative interpretation of the results is given on the basis of the Gouy-Chapman theory. The results indicate that the dansyl chromophore is located in front of the charged surface and its distance from this surface increases with a decrease in lipid packing."}
{"id": "PMID:23948", "title": "Kinetics of carbon monoxide binding to fully and partially reduced human hemoglobin valency hybrids.", "content": "The kinetics of carbon monoxide binding following fast reduction of the valency hybrids alpha2+betaCO2 and alphaCO2beta+2 by hydrated electrons have been studied at different degrees of reduction. The results show that at pH 6.0 and 7.0 reduction of one heme group yields a species which reacts fast with carbon monoxide (rate constant of the order of 10(6) M-1S-1). At pH 6.0 the intermediates alphaCO2beta2 and alpha2betaCO2 bind carbon monoxide with a rate characteristic of the T state. At pH 7.0 alphaCO2beta2 is for the greater part in the T state, while in the case of alpha2betaCO2 the R and the T state are about equally populated.", "contents": "Kinetics of carbon monoxide binding to fully and partially reduced human hemoglobin valency hybrids. The kinetics of carbon monoxide binding following fast reduction of the valency hybrids alpha2+betaCO2 and alphaCO2beta+2 by hydrated electrons have been studied at different degrees of reduction. The results show that at pH 6.0 and 7.0 reduction of one heme group yields a species which reacts fast with carbon monoxide (rate constant of the order of 10(6) M-1S-1). At pH 6.0 the intermediates alphaCO2beta2 and alpha2betaCO2 bind carbon monoxide with a rate characteristic of the T state. At pH 7.0 alphaCO2beta2 is for the greater part in the T state, while in the case of alpha2betaCO2 the R and the T state are about equally populated."}
{"id": "PMID:23949", "title": "Mg2+ translocation across the thylakoid membrane: studies using the ionophore A 23187.", "content": "1. The degree of the light-dependent Mg2+ efflux across the thylakoid membrane is a function of pH. There is a considerable efflux at pH 7.2 which decreases to a negligible amount at pH 8.6. This conclusion is derived from studies using the divalent cation-specific ionophore A23187. The ionophore is active as an uncoupler at pH 7.2 even in the absence of added Mg2+, and completely inactive at pH 8.6 unless Mg2+ is added. The activity was assayed as the effect on both the rate of electron transport (stimulation at pH 7.2 and inhibition at pH 8.6) and deltapH. 2. Under conditions of maximal Mg2+ efflux, pH 7.2, and in the presence of EDTA, it is shown that Mg2+ is transported across the thylakoid membrane, but it is not diluted in the medium. 3. At high pH, light-induced proton influx is not compensated by Mg2+ efflux in the presence of a relatively permeable anion. However, in the presence of an impermeable anion, where cation efflux is necessary, Mg2+ efflux occurs, indicating its preference to K+ efflux. It is suggested that although light-induced Mg2+ efflux across the thylakoid membrane is evident, its magnitude is small and it is not diluted in the stroma. Thus, it seems hard to visualize how this transport is supposed to play an important role in CO2 fixation.", "contents": "Mg2+ translocation across the thylakoid membrane: studies using the ionophore A 23187. 1. The degree of the light-dependent Mg2+ efflux across the thylakoid membrane is a function of pH. There is a considerable efflux at pH 7.2 which decreases to a negligible amount at pH 8.6. This conclusion is derived from studies using the divalent cation-specific ionophore A23187. The ionophore is active as an uncoupler at pH 7.2 even in the absence of added Mg2+, and completely inactive at pH 8.6 unless Mg2+ is added. The activity was assayed as the effect on both the rate of electron transport (stimulation at pH 7.2 and inhibition at pH 8.6) and deltapH. 2. Under conditions of maximal Mg2+ efflux, pH 7.2, and in the presence of EDTA, it is shown that Mg2+ is transported across the thylakoid membrane, but it is not diluted in the medium. 3. At high pH, light-induced proton influx is not compensated by Mg2+ efflux in the presence of a relatively permeable anion. However, in the presence of an impermeable anion, where cation efflux is necessary, Mg2+ efflux occurs, indicating its preference to K+ efflux. It is suggested that although light-induced Mg2+ efflux across the thylakoid membrane is evident, its magnitude is small and it is not diluted in the stroma. Thus, it seems hard to visualize how this transport is supposed to play an important role in CO2 fixation."}
{"id": "PMID:23950", "title": "Therapeutic and collateral effects of 25-hydroxycholecalciferol in vitamin D deficiency.", "content": "The clinical and biochemical response to 25-hydroxycholecalciferol (25-HCC) and vitamin D3, 150 microgram/day for 20 days has been compared in infants aged 3--18 months with nutritional rickets. The infants were allocated at random to Group I (11 infants) treated with 25HCC and Group II (9 infants) treated with vitamin D3. In addition 15 matched control children without rickets were allocated to Group III and received 25-HCC 75 microgram/day for 20 days. Preliminary studies showed that plasma calcium, phosphorus, alkaline phosphatase and urine pH all differed significantly between the rachitic and control groups. The biochemical parameters in both groups of rachitic children became normal after treatment with the exception of plasma alkaline phosphatase which remained elevated. The control group showed a significant increase in plasma and urine calcium values in spite of the low dose of 25-HCC. The findings suggest that 25-HCC is as effective as vitamin D3 in the treatment of rickets but did not demonstrate any therapeutic advantage.", "contents": "Therapeutic and collateral effects of 25-hydroxycholecalciferol in vitamin D deficiency. The clinical and biochemical response to 25-hydroxycholecalciferol (25-HCC) and vitamin D3, 150 microgram/day for 20 days has been compared in infants aged 3--18 months with nutritional rickets. The infants were allocated at random to Group I (11 infants) treated with 25HCC and Group II (9 infants) treated with vitamin D3. In addition 15 matched control children without rickets were allocated to Group III and received 25-HCC 75 microgram/day for 20 days. Preliminary studies showed that plasma calcium, phosphorus, alkaline phosphatase and urine pH all differed significantly between the rachitic and control groups. The biochemical parameters in both groups of rachitic children became normal after treatment with the exception of plasma alkaline phosphatase which remained elevated. The control group showed a significant increase in plasma and urine calcium values in spite of the low dose of 25-HCC. The findings suggest that 25-HCC is as effective as vitamin D3 in the treatment of rickets but did not demonstrate any therapeutic advantage."}
{"id": "PMID:23952", "title": "The contribution of intestinal endotoxin to mortality in hosts with compromised resistance: a review.", "content": "Sepsis, particularly with endotoxin-containing Gram-negative bacilli, is a serious complication in hosts whose defenses are compromised. This review examines work from our laboratory and others concerning infectious processes which may be critical to the survival of compromised individuals. Several avenues for control of sepsis are proposed. Gram-negative bacteria and their endotoxins can escape from the intestines of compromised animals to contaminate normally sterile host tissues. Endotoxins are especially toxic to compromised hosts because essential components of their inflammatory responses are missing (i.e., leukocytes and platelets in irradiated animals). Therefore, regulation of host responses to endotoxin is no longer possible. It is recommended that sepsis be controlled in compromised individuals through elimination of endogenous microbial agents. Should infection occur in these individuals, they should be transfused with blood cells necessary for clearance of bacteria and endotoxin and restoration of homeostasis.", "contents": "The contribution of intestinal endotoxin to mortality in hosts with compromised resistance: a review. Sepsis, particularly with endotoxin-containing Gram-negative bacilli, is a serious complication in hosts whose defenses are compromised. This review examines work from our laboratory and others concerning infectious processes which may be critical to the survival of compromised individuals. Several avenues for control of sepsis are proposed. Gram-negative bacteria and their endotoxins can escape from the intestines of compromised animals to contaminate normally sterile host tissues. Endotoxins are especially toxic to compromised hosts because essential components of their inflammatory responses are missing (i.e., leukocytes and platelets in irradiated animals). Therefore, regulation of host responses to endotoxin is no longer possible. It is recommended that sepsis be controlled in compromised individuals through elimination of endogenous microbial agents. Should infection occur in these individuals, they should be transfused with blood cells necessary for clearance of bacteria and endotoxin and restoration of homeostasis."}
{"id": "PMID:23956", "title": "Simultaneous monitoring by optical techniques of respiratory chain and intracellular pH in toad ventricle strip.", "content": "Intracellular pH and oxidative metabolism can be measured in toad ventricle strips simultaneously by the use of the pH indicator dye, neutral red, and a rapid scanning spectrophotometer. The effects of hypoxia and acidification on mechanical function are approximately additive. The decrease in tension due to slight acidification is probably through an effect on the portion of the twitch tension supported by anaerobic metabolism.", "contents": "Simultaneous monitoring by optical techniques of respiratory chain and intracellular pH in toad ventricle strip. Intracellular pH and oxidative metabolism can be measured in toad ventricle strips simultaneously by the use of the pH indicator dye, neutral red, and a rapid scanning spectrophotometer. The effects of hypoxia and acidification on mechanical function are approximately additive. The decrease in tension due to slight acidification is probably through an effect on the portion of the twitch tension supported by anaerobic metabolism."}
{"id": "PMID:23957", "title": "[Nature of the melipramine inhibition of the K+-n-nitrophenyl phosphatase activity of a synaptosomal fraction].", "content": "The influence of antidepressant melipramine (imipramine) on the K+-paranitrophenyl-phosphatase (K+-n-NFP-ase) activity of the synaptosomal fraction in the bull's brain cortex, treated with sodium iodide, was studied in in vitro experiments. Melipramine (5.10(-5)--10(-3)M) is shown to inhibit the K+-n-NFP-ase activity, competing with potassium ions. With pH changing from acid and neutral to alkaline values the inhibitory action of melipramine gains in intensity, whereas the protective effect of potassium ions declines. It is suggested that one of the mechanisms responsible for the inhibition of the K+-p-NFP-ase activity by melipramine is interaction of the inhibitor in the anionic sections of the enzyme complex.", "contents": "[Nature of the melipramine inhibition of the K+-n-nitrophenyl phosphatase activity of a synaptosomal fraction]. The influence of antidepressant melipramine (imipramine) on the K+-paranitrophenyl-phosphatase (K+-n-NFP-ase) activity of the synaptosomal fraction in the bull's brain cortex, treated with sodium iodide, was studied in in vitro experiments. Melipramine (5.10(-5)--10(-3)M) is shown to inhibit the K+-n-NFP-ase activity, competing with potassium ions. With pH changing from acid and neutral to alkaline values the inhibitory action of melipramine gains in intensity, whereas the protective effect of potassium ions declines. It is suggested that one of the mechanisms responsible for the inhibition of the K+-p-NFP-ase activity by melipramine is interaction of the inhibitor in the anionic sections of the enzyme complex."}
{"id": "PMID:23958", "title": "[Effect of pharmacological substances on the development of hemorrhagic erosions and on the noradrenaline level in the stomach wall in rats].", "content": "Hemorrhagic erosions of the gastric mucosa were produced through electric stimulation of immobilized rats via electrodes stuck into the muscles of the fore-paws. In the experiment there was applied square pulsed current of 5--7 v (per 10 rats) with frequency of 50 Hz and the pulse time of 10 ms. Prior to stimulation the rats received intraperitoneally one of the following drugs: clonidin (0.1 mg/kg), benactyzine (3 mg/kg), etherophen (20 mg/kg), benzohexonium (10 mg/kg), iprazid (100 mg/kg), amphethamine (4 mg/kg), atropine (1 mg/kg), tyrosine (300 mg/kg), aethimizol (10 mg/kg) and orotic acid (10 mg/kg). The animals were sacrificed directly after stimulation and the norepinephrine level in the gastric wall was determined after E. Sh. Matlina and T. B. Rakhmanova (1967). Introduction of clonidin, benacyzine, etherophen, benzohexonium and iprazid to immobilized rats after electric stimulation prevented the development of hemorrhagic erosions and a drop of the norepinephrine level in the gastric wall, whereas amphethamine and tyrosine intensified the process of the erosions development in the gastric mucosa and did not prevent a decline in the norepinephrine level. Atropine and aethimizol had no effect on the findings under study.", "contents": "[Effect of pharmacological substances on the development of hemorrhagic erosions and on the noradrenaline level in the stomach wall in rats]. Hemorrhagic erosions of the gastric mucosa were produced through electric stimulation of immobilized rats via electrodes stuck into the muscles of the fore-paws. In the experiment there was applied square pulsed current of 5--7 v (per 10 rats) with frequency of 50 Hz and the pulse time of 10 ms. Prior to stimulation the rats received intraperitoneally one of the following drugs: clonidin (0.1 mg/kg), benactyzine (3 mg/kg), etherophen (20 mg/kg), benzohexonium (10 mg/kg), iprazid (100 mg/kg), amphethamine (4 mg/kg), atropine (1 mg/kg), tyrosine (300 mg/kg), aethimizol (10 mg/kg) and orotic acid (10 mg/kg). The animals were sacrificed directly after stimulation and the norepinephrine level in the gastric wall was determined after E. Sh. Matlina and T. B. Rakhmanova (1967). Introduction of clonidin, benacyzine, etherophen, benzohexonium and iprazid to immobilized rats after electric stimulation prevented the development of hemorrhagic erosions and a drop of the norepinephrine level in the gastric wall, whereas amphethamine and tyrosine intensified the process of the erosions development in the gastric mucosa and did not prevent a decline in the norepinephrine level. Atropine and aethimizol had no effect on the findings under study."}
{"id": "PMID:23959", "title": "[Rat placental barrier permeability for the new antihistaminic preparation, fenkarol].", "content": "As established, following a single introduction of phencarol tagged with tritium in a quinuclidine nucleus perorally to rats on the 13th day of gestation its insignificant amounts gain access to the fetus through the placenta. The maximum concentration of the drug in the maternal blood was recorded 3 hours after its introduction, following 6 hours--in the placenta, with the radioactivity continuing to be constant during the first 6 hours in the embryonal tissues. In 48 hours after introduction the radioactive tag is still demonstrable in the study tissues. It is concluded that the drug is largely retained in the placenta, when introduced on the 13th day of pregnancy; on the 21st day of gestation the barrier functions of the placenta declines. The presence of phencarol and its transformation products in the embryonal tissues is confirmed by the method of thin-layer chromotography.", "contents": "[Rat placental barrier permeability for the new antihistaminic preparation, fenkarol]. As established, following a single introduction of phencarol tagged with tritium in a quinuclidine nucleus perorally to rats on the 13th day of gestation its insignificant amounts gain access to the fetus through the placenta. The maximum concentration of the drug in the maternal blood was recorded 3 hours after its introduction, following 6 hours--in the placenta, with the radioactivity continuing to be constant during the first 6 hours in the embryonal tissues. In 48 hours after introduction the radioactive tag is still demonstrable in the study tissues. It is concluded that the drug is largely retained in the placenta, when introduced on the 13th day of pregnancy; on the 21st day of gestation the barrier functions of the placenta declines. The presence of phencarol and its transformation products in the embryonal tissues is confirmed by the method of thin-layer chromotography."}
{"id": "PMID:23960", "title": "[Effect of the structure of liposomal membrane surface layer on the binding of phenothiazines].", "content": "By using a fluorescent 3-metoxybenzatrone probe the binding of the phenothiazine series drugs (chlorpromazine, triftazine, aethaperazine) with phospholipid vesicles--liposomes, was investigated. Cholesterol is shown not to affect the binding of these drugs with liposomes. The surface charge of liposomes influences only the combination with the chlorpromazine membranes. With a higher positive charge of the membranes the binding of chlorpromazine diminishes in force.", "contents": "[Effect of the structure of liposomal membrane surface layer on the binding of phenothiazines]. By using a fluorescent 3-metoxybenzatrone probe the binding of the phenothiazine series drugs (chlorpromazine, triftazine, aethaperazine) with phospholipid vesicles--liposomes, was investigated. Cholesterol is shown not to affect the binding of these drugs with liposomes. The surface charge of liposomes influences only the combination with the chlorpromazine membranes. With a higher positive charge of the membranes the binding of chlorpromazine diminishes in force."}
{"id": "PMID:23965", "title": "Acetylcholine--inhibition of transmitter release from adrenergic nerve terminals mediated by muscarinic receptors.", "content": "The evidence is reviewed for the presence of muscarinic receptors on the sympathetic nerves to blood vessels. Activation of these receptors by acetylcholine in doses that are too small to affect the smooth muscle cells directly inhibits the release of norepinephrine evoked by electric impulses or potassium ions. This inhibitory action of acetylcholine is prevented by muscarinic blocking agents and is probably due to hyperpolarization of the adrenergic nerve terminals.", "contents": "Acetylcholine--inhibition of transmitter release from adrenergic nerve terminals mediated by muscarinic receptors. The evidence is reviewed for the presence of muscarinic receptors on the sympathetic nerves to blood vessels. Activation of these receptors by acetylcholine in doses that are too small to affect the smooth muscle cells directly inhibits the release of norepinephrine evoked by electric impulses or potassium ions. This inhibitory action of acetylcholine is prevented by muscarinic blocking agents and is probably due to hyperpolarization of the adrenergic nerve terminals."}
{"id": "PMID:23966", "title": "Histamine and 5-hydroxytryptamine-inhibition of transmitter release mediated by H2- and 5-hydroxytryptamine receptors.", "content": "The vasodilatation caused by histamine and 5-hydroxytryptamine may be due, at least in part, to their inhibitory action on adrenergic neurotransmission. The evidence for this is as follows: 1) contractions of isolated canine vascular strips caused by sympathetic nerve stimulation are depressed by these substances whereas contractions caused by norepinephrine are either unchanged or augmented; 2) histamine and 5-hydroxytryptamine inhibit the release of norepinephrine evoked by sympathetic nerve stimulation of isolated vascular strips previously incubated with the labeled transmitter. This inhibitory effect can be demonstrated using concentrations of the substinces less than those required to affect the smooth muscle cells directly. By contrast, neither histamine nor 5-hydroxytryptamine inhibits the displacement of neuronal norepinephrine by tyramine, suggesting that these substances interfere with the exocytotic process. Additional studies have identified the histamine-H2 receptor as the probable mediator of this prejunctional action of histamine, whereas the nature of the receptor for 5-hydroxytryptamine remains to be clarified.", "contents": "Histamine and 5-hydroxytryptamine-inhibition of transmitter release mediated by H2- and 5-hydroxytryptamine receptors. The vasodilatation caused by histamine and 5-hydroxytryptamine may be due, at least in part, to their inhibitory action on adrenergic neurotransmission. The evidence for this is as follows: 1) contractions of isolated canine vascular strips caused by sympathetic nerve stimulation are depressed by these substances whereas contractions caused by norepinephrine are either unchanged or augmented; 2) histamine and 5-hydroxytryptamine inhibit the release of norepinephrine evoked by sympathetic nerve stimulation of isolated vascular strips previously incubated with the labeled transmitter. This inhibitory effect can be demonstrated using concentrations of the substinces less than those required to affect the smooth muscle cells directly. By contrast, neither histamine nor 5-hydroxytryptamine inhibits the displacement of neuronal norepinephrine by tyramine, suggesting that these substances interfere with the exocytotic process. Additional studies have identified the histamine-H2 receptor as the probable mediator of this prejunctional action of histamine, whereas the nature of the receptor for 5-hydroxytryptamine remains to be clarified."}
{"id": "PMID:23967", "title": "Actions of angiotensin on adrenergic nerve endings.", "content": "In the perfused vascular bed, vasoconstrictor responses to adrenergic nerve stimulation are augmented to a greater degree by angiotensin II than are the responses to injected norepinephrine. Overflow of adrenergic transmitter is also greater during nerve stimulation in the presence of angiotensin than in its absence. The evidence indicates that facilitation of adrenergic transmitter release rather than uptake blockade accounts for these results. In addition, an increased responsiveness of isolated arterial strips to norepinephrine as well as other agonists appears to contribute to the adrenergic potentiating effect of angiotensin II as well as angiotensin III. This action, which appears to be a cell membrane effect, seems to participate in adrenergic potentiation mainly in the arterial segment of the intact vascular bed. Both of these effects of angiotensin, i.e., facilitation of release and increased smooth muscle responsiveness, appear to be mediated by angiotensin receptors.", "contents": "Actions of angiotensin on adrenergic nerve endings. In the perfused vascular bed, vasoconstrictor responses to adrenergic nerve stimulation are augmented to a greater degree by angiotensin II than are the responses to injected norepinephrine. Overflow of adrenergic transmitter is also greater during nerve stimulation in the presence of angiotensin than in its absence. The evidence indicates that facilitation of adrenergic transmitter release rather than uptake blockade accounts for these results. In addition, an increased responsiveness of isolated arterial strips to norepinephrine as well as other agonists appears to contribute to the adrenergic potentiating effect of angiotensin II as well as angiotensin III. This action, which appears to be a cell membrane effect, seems to participate in adrenergic potentiation mainly in the arterial segment of the intact vascular bed. Both of these effects of angiotensin, i.e., facilitation of release and increased smooth muscle responsiveness, appear to be mediated by angiotensin receptors."}
{"id": "PMID:23968", "title": "Prostaglandins--modulation of adrenergic nervous system.", "content": "Prostaglandins (PGs) affect vascular tone by a direct action on the vascular smooth muscle and by influencing vascular reactivity to adrenergic simuli and several vasoactive substances. Thus, in the isolated Tyrode's perfused rabbit renal, mesenteric and splenic vasculature PGE2 inhibited adrenergically induced vasoconstriction. Since the vasoconstrictor responses to renal nerve stimulation were enhanced by the blockade of PG synthesis and were reduced by stimulation of PG synthesis with arachidonic acid, this suggests that PGE2 functions as an inhibitory modulator of the adrenergic nervous system. However, our demonstration that PGE2 enhanced adrenergically induced vasoconstriction in the renal and mesenteric vasculature of the rat, but had opposite effects in the rat splenic vasculature indicates that the modulatory-effect of PGE-compounds on the adrenergic neuromuscular junction is species dependent and varies in different vascular beds within the same species. Prostaglandins, the release of which is evoked by several vasoactive substances including angiotensins, kinins, and adenine nucleotides, may also contribute to the regulation of vascular tone by either opposing or amplifying the vascular actions of vasoactive substances.", "contents": "Prostaglandins--modulation of adrenergic nervous system. Prostaglandins (PGs) affect vascular tone by a direct action on the vascular smooth muscle and by influencing vascular reactivity to adrenergic simuli and several vasoactive substances. Thus, in the isolated Tyrode's perfused rabbit renal, mesenteric and splenic vasculature PGE2 inhibited adrenergically induced vasoconstriction. Since the vasoconstrictor responses to renal nerve stimulation were enhanced by the blockade of PG synthesis and were reduced by stimulation of PG synthesis with arachidonic acid, this suggests that PGE2 functions as an inhibitory modulator of the adrenergic nervous system. However, our demonstration that PGE2 enhanced adrenergically induced vasoconstriction in the renal and mesenteric vasculature of the rat, but had opposite effects in the rat splenic vasculature indicates that the modulatory-effect of PGE-compounds on the adrenergic neuromuscular junction is species dependent and varies in different vascular beds within the same species. Prostaglandins, the release of which is evoked by several vasoactive substances including angiotensins, kinins, and adenine nucleotides, may also contribute to the regulation of vascular tone by either opposing or amplifying the vascular actions of vasoactive substances."}
{"id": "PMID:23969", "title": "Metabolic modulation of neurotransmitter release--adenosine, adenine nucleotides, potassium, hyperosmolarity, and hydrogen ion.", "content": "Evidence has accumulated that several factors, which have been proposed as mediators of exercise hyperemia, can modulate adrenergic neurotransmission in blood vessels. Adenosine and the adenine nucleotides depress the response of isolated blood vessels of the dog to nerve stimulation more than that to exogenous norepinephrine; this difference is explained by a decreased release of the neurotransmitter. Potassium, hyperosmolarity, and acidosis also depress adrenergic neurotransmission in isolated veins. These results are consistent with the hypothesis that metabolic changes in the vicinity of the adrenergic neuroeffector junction are capable of decreasing the output of neurotransmitter to the blood vessels in the exercising muscle.", "contents": "Metabolic modulation of neurotransmitter release--adenosine, adenine nucleotides, potassium, hyperosmolarity, and hydrogen ion. Evidence has accumulated that several factors, which have been proposed as mediators of exercise hyperemia, can modulate adrenergic neurotransmission in blood vessels. Adenosine and the adenine nucleotides depress the response of isolated blood vessels of the dog to nerve stimulation more than that to exogenous norepinephrine; this difference is explained by a decreased release of the neurotransmitter. Potassium, hyperosmolarity, and acidosis also depress adrenergic neurotransmission in isolated veins. These results are consistent with the hypothesis that metabolic changes in the vicinity of the adrenergic neuroeffector junction are capable of decreasing the output of neurotransmitter to the blood vessels in the exercising muscle."}
{"id": "PMID:23973", "title": "Oxypertine in combination with imipramine: a controlled trial.", "content": "A method for the controlled assessment of two agents for possible interaction in the treatment of endogenous depression is described. This consisted of dose-ranging the supplementary agent (oxypertine 30 mg and 60 mg daily or matching placebo) during Week 2 to Week 6 having established all patients on a therapeutic dose of imipramine during Week 1. The reported enhancement of imipramine by oxypertine was not confirmed.", "contents": "Oxypertine in combination with imipramine: a controlled trial. A method for the controlled assessment of two agents for possible interaction in the treatment of endogenous depression is described. This consisted of dose-ranging the supplementary agent (oxypertine 30 mg and 60 mg daily or matching placebo) during Week 2 to Week 6 having established all patients on a therapeutic dose of imipramine during Week 1. The reported enhancement of imipramine by oxypertine was not confirmed."}
{"id": "PMID:23974", "title": "Studies of the androgen binding protein in the rete testis fluid of the ram and its relation to sexual season.", "content": "An androgen binding protein (ABP) with an electrophoretic mobility (Rf) of 0.56 is present in the rete testis fluid of adult rams. Its steroid specificity was found to be in the following order: 5alpha-DHT, testosterone, oestradiol-17 beta, dehydroepiandrosterone 5beta-DHT, androstenedione, cyproterone, cyproterone acetate, cortisol and progesterone. The characteristics of the ABP are similar to those found for the ABP of the testis and the epididymis of the rat and the rabbit. The concentration of ABP, determined by the dextran-coated charcoal method and sometimes confirmed by the steady-state polyacrylamide gel electrophoresis method, was significantly higher in the breeding season than in the non-breeding season (4.40 +/- 0.98 X 10(-9) M vs. 2.60 +/- 0.62 X 10(-9) M; P less than 0.037). The affinity constant of the ABP was independent of the season (2.45 +/- 0.21 X 10(9) M-1 vs. 2.66 +/- 0.1 X 10(9) M-1; NS). In addition, ABP was positively correlated with 5alpha-DHT (r = 0.506; P  less than 0.0009), testosterone (r = 0.445; P less than 0.0003), total protein (r = 0.329; P less than 0.02) and spermatozoa (r = 0.406; P less than 0.006) in the RTF and with blood plasma testosterone (r = 0.584; P less than 0.0001). Furthermore, testosterone and 5alpha-DHT in RTF were positively correlated (r = 0.582; P less than 0.0001). These androgens were also correlated with plasma testosterone (r = 0.262, P less than 0.052 for testosterone in RTF; r = 0.341, P less than 0.018 for 5 alpha-DHT). Total proteins and spermatozoa were found to be positively correlated in the RTF (r = 0.789; P less than 0.0001).", "contents": "Studies of the androgen binding protein in the rete testis fluid of the ram and its relation to sexual season. An androgen binding protein (ABP) with an electrophoretic mobility (Rf) of 0.56 is present in the rete testis fluid of adult rams. Its steroid specificity was found to be in the following order: 5alpha-DHT, testosterone, oestradiol-17 beta, dehydroepiandrosterone 5beta-DHT, androstenedione, cyproterone, cyproterone acetate, cortisol and progesterone. The characteristics of the ABP are similar to those found for the ABP of the testis and the epididymis of the rat and the rabbit. The concentration of ABP, determined by the dextran-coated charcoal method and sometimes confirmed by the steady-state polyacrylamide gel electrophoresis method, was significantly higher in the breeding season than in the non-breeding season (4.40 +/- 0.98 X 10(-9) M vs. 2.60 +/- 0.62 X 10(-9) M; P less than 0.037). The affinity constant of the ABP was independent of the season (2.45 +/- 0.21 X 10(9) M-1 vs. 2.66 +/- 0.1 X 10(9) M-1; NS). In addition, ABP was positively correlated with 5alpha-DHT (r = 0.506; P  less than 0.0009), testosterone (r = 0.445; P less than 0.0003), total protein (r = 0.329; P less than 0.02) and spermatozoa (r = 0.406; P less than 0.006) in the RTF and with blood plasma testosterone (r = 0.584; P less than 0.0001). Furthermore, testosterone and 5alpha-DHT in RTF were positively correlated (r = 0.582; P less than 0.0001). These androgens were also correlated with plasma testosterone (r = 0.262, P less than 0.052 for testosterone in RTF; r = 0.341, P less than 0.018 for 5 alpha-DHT). Total proteins and spermatozoa were found to be positively correlated in the RTF (r = 0.789; P less than 0.0001)."}
{"id": "PMID:23976", "title": "Animal influenza virus neuraminidase: studies on dependence of some of its properties on its association with hemagglutinin.", "content": "Neuraminidase (Nase) thermostability and sensitivity to pH treatment as well as specific enzymatic activity (Nase activity per 1 HA unit) were determined in two groups of animal influenza virus strains containing equine 1 and equine 2 Nase subtypes, respectively (A/equine/Prague/56 (Heq1 Neq1), A/equine/Cambridge/63 (Heq1 Neq1), A/FPV/Dutch/34 (Hav1 Neq1), A/chicken/Germany \"N\" (Hav2 Neq1), in one group, and A/equine/Miami/1/63 (Heq2 Neq2), A/turkey/Canada/63 (Hav6 Neq2), A/duck/Ukraine/1/63 (Hav7 Neq2), in the other group). Nase of all the strains used was thermotabile when heated at pH 4.5. Nase of Neq1 subtype irrespective of strain containing it was thermolabilt when heated both at pH 6.5 and 8.1 and sensitive to pH 4.5 treatment as such (without heating). Inversely, Nase of Neq2 antigenic subtype irrespective of the strain containing it, was thermostable when heated at pH 6.5 AND 8.1 and resistant to the treatment of pH 4.5. Specific enzymatic activity was considerably higher in all the strains containing Neq2 as compared to Neq1-containing strains (4-6 times as much). The results suggest that thermostability and pH sensitivity of equine Nases of both antigenic subtypes, as well as their specific activities, do not depend on the sort of HA which is coupled with enzyme subunits at viral envelope, but attributed rather to properties of the subunits themselves, such as glycoprotein entities. The data concerning specific activities may suggest that in the case of various combinations of Nase subunits with different HA subunits the amount of enzyme per virion is of the same order.", "contents": "Animal influenza virus neuraminidase: studies on dependence of some of its properties on its association with hemagglutinin. Neuraminidase (Nase) thermostability and sensitivity to pH treatment as well as specific enzymatic activity (Nase activity per 1 HA unit) were determined in two groups of animal influenza virus strains containing equine 1 and equine 2 Nase subtypes, respectively (A/equine/Prague/56 (Heq1 Neq1), A/equine/Cambridge/63 (Heq1 Neq1), A/FPV/Dutch/34 (Hav1 Neq1), A/chicken/Germany \"N\" (Hav2 Neq1), in one group, and A/equine/Miami/1/63 (Heq2 Neq2), A/turkey/Canada/63 (Hav6 Neq2), A/duck/Ukraine/1/63 (Hav7 Neq2), in the other group). Nase of all the strains used was thermotabile when heated at pH 4.5. Nase of Neq1 subtype irrespective of strain containing it was thermolabilt when heated both at pH 6.5 and 8.1 and sensitive to pH 4.5 treatment as such (without heating). Inversely, Nase of Neq2 antigenic subtype irrespective of the strain containing it, was thermostable when heated at pH 6.5 AND 8.1 and resistant to the treatment of pH 4.5. Specific enzymatic activity was considerably higher in all the strains containing Neq2 as compared to Neq1-containing strains (4-6 times as much). The results suggest that thermostability and pH sensitivity of equine Nases of both antigenic subtypes, as well as their specific activities, do not depend on the sort of HA which is coupled with enzyme subunits at viral envelope, but attributed rather to properties of the subunits themselves, such as glycoprotein entities. The data concerning specific activities may suggest that in the case of various combinations of Nase subunits with different HA subunits the amount of enzyme per virion is of the same order."}
{"id": "PMID:23982", "title": "Assessment of the plasma disappearance of cholyl'l14C-glycine as a test of hepatocellular disease.", "content": "The plasma disappearance of a tracer dose of cholyl-l14C-glycine has been examined in 12 control subjects and in 32 patients with hepatocellular dysfunction. Simple analysis of the data did not detect hepatic dysfunction except in severe hepatocellular disease. The greatest degree of discrimination between normal subjects and patients with mild liver disease was obtained by taking the ratio of the plasma retention at 60 minutes to that at 10 minutes; it was similar to that obtained with serum gamma-glutamyl transferase. The two hour post-prandial plasma \"total\" bile acid concentration gave complete separation between the control subjects and patients with liver disease.", "contents": "Assessment of the plasma disappearance of cholyl'l14C-glycine as a test of hepatocellular disease. The plasma disappearance of a tracer dose of cholyl-l14C-glycine has been examined in 12 control subjects and in 32 patients with hepatocellular dysfunction. Simple analysis of the data did not detect hepatic dysfunction except in severe hepatocellular disease. The greatest degree of discrimination between normal subjects and patients with mild liver disease was obtained by taking the ratio of the plasma retention at 60 minutes to that at 10 minutes; it was similar to that obtained with serum gamma-glutamyl transferase. The two hour post-prandial plasma \"total\" bile acid concentration gave complete separation between the control subjects and patients with liver disease."}
{"id": "PMID:23983", "title": "Postprandial gastro-oesophageal reflux in healthy people.", "content": "Distal oesophageal pH was monitored for three hours after a standard meal in 10 young healthy subjects without symptoms of gastro-oesophageal reflux. Episodes of reflux occurred in nine of these subjects; and, in five, oesophageal pH was less than 5 for between 11 and 75% of the first postprandial hour. Intermittent incompetence of the lower oesophageal sphincter after food must, therefore, be regarded as a normal phenomenon. The method described would be suitable for the evaluation of agents believed to weaken or to strengthen the lower oesophageal sphincter.", "contents": "Postprandial gastro-oesophageal reflux in healthy people. Distal oesophageal pH was monitored for three hours after a standard meal in 10 young healthy subjects without symptoms of gastro-oesophageal reflux. Episodes of reflux occurred in nine of these subjects; and, in five, oesophageal pH was less than 5 for between 11 and 75% of the first postprandial hour. Intermittent incompetence of the lower oesophageal sphincter after food must, therefore, be regarded as a normal phenomenon. The method described would be suitable for the evaluation of agents believed to weaken or to strengthen the lower oesophageal sphincter."}
{"id": "PMID:23984", "title": "Transport kinetics of 6-deoxy-D-glucose in Candida parapsilosis.", "content": "The strictly aerobic yeast Candida parapsilosis transports the nonmetabolizable monosaccharide 6-deoxy-D-glucose by an active process (inhibition by 2.4-dinitrophenol and other uncouplers but not by iodoacetamide), the accumulation ratio decreasing with increasing substrate concentration. Measured accumulation ratios are in agreement with those predicted from kinetic constants for influx and efflux. Energy for transport is probably required in the translocation step. The maximum rate is temperature-dependent with a transition point at 21 degrees C. the accumulation ratio is not. The uptake is most active at pH 4.5--8.5. It appears not to involve stoichiometric proton symport. The transport system is shared by D-glucose, D-mannose, D-galactose and possibly maltose but not by fructose, sucrose or pentoses. The apparent half-life of the transport system was 3.5--4 h.", "contents": "Transport kinetics of 6-deoxy-D-glucose in Candida parapsilosis. The strictly aerobic yeast Candida parapsilosis transports the nonmetabolizable monosaccharide 6-deoxy-D-glucose by an active process (inhibition by 2.4-dinitrophenol and other uncouplers but not by iodoacetamide), the accumulation ratio decreasing with increasing substrate concentration. Measured accumulation ratios are in agreement with those predicted from kinetic constants for influx and efflux. Energy for transport is probably required in the translocation step. The maximum rate is temperature-dependent with a transition point at 21 degrees C. the accumulation ratio is not. The uptake is most active at pH 4.5--8.5. It appears not to involve stoichiometric proton symport. The transport system is shared by D-glucose, D-mannose, D-galactose and possibly maltose but not by fructose, sucrose or pentoses. The apparent half-life of the transport system was 3.5--4 h."}
{"id": "PMID:23985", "title": "Production of amylase by a submerged culture of Aspergillus wentii.", "content": "Soluble starch was hydrolysed to maltose by Aspergillus wentii Wehmer (IMI 17295). Studies on nutritional requirements of Aspergillus wentii for production of amylase revealed that the optimum conditions were achieved in fermentation culture medium containing 1% starch, and incubated at 20 degrees C for 3 days at pH 6.0. Tryptophan was the best nitrogen source. The amylase activity was completely inhibited when 1 mM sodium iodoacetate was incorporated into the medium. With 10 mM sodium citrate the amylase activity was increased from 3.51 to 6.0 mg/ml.", "contents": "Production of amylase by a submerged culture of Aspergillus wentii. Soluble starch was hydrolysed to maltose by Aspergillus wentii Wehmer (IMI 17295). Studies on nutritional requirements of Aspergillus wentii for production of amylase revealed that the optimum conditions were achieved in fermentation culture medium containing 1% starch, and incubated at 20 degrees C for 3 days at pH 6.0. Tryptophan was the best nitrogen source. The amylase activity was completely inhibited when 1 mM sodium iodoacetate was incorporated into the medium. With 10 mM sodium citrate the amylase activity was increased from 3.51 to 6.0 mg/ml."}
{"id": "PMID:23988", "title": "Parallel occurrence of oxidant-sensitivity and decreased inhibition by NADPH in G-6-PD Lublin and G-6-PD Poxna\u0144.", "content": "In two studied variants of G-6-PD without chronic hemolysis in probands, sensitivity of enzymes to inhibition by NADPH was decreased. Ki for NADPH was 28 micronM in Gd Lublin and 19 micronM in Gd Pozna\u0144. Susceptibility to the oxidant-induced hemolysis was described in probands, as well as in patients hemizygous for two other variants of G-6-PD with increased Ki for NADPH. It is suggested that in these cases, the oxidant-induced hemolysis is aggravated by their inability to counteract the drop in NADPH concentration with an increase in G-6-PD activity.", "contents": "Parallel occurrence of oxidant-sensitivity and decreased inhibition by NADPH in G-6-PD Lublin and G-6-PD Poxna\u0144. In two studied variants of G-6-PD without chronic hemolysis in probands, sensitivity of enzymes to inhibition by NADPH was decreased. Ki for NADPH was 28 micronM in Gd Lublin and 19 micronM in Gd Pozna\u0144. Susceptibility to the oxidant-induced hemolysis was described in probands, as well as in patients hemizygous for two other variants of G-6-PD with increased Ki for NADPH. It is suggested that in these cases, the oxidant-induced hemolysis is aggravated by their inability to counteract the drop in NADPH concentration with an increase in G-6-PD activity."}
{"id": "PMID:23989", "title": "Studies of cyclic AMP action using mutant tissue culture cells.", "content": "S49 mouse lymphoma cell mutants, each with a specific defect in its ability to generate or respond to cyclic AMP, have been isolated. Analysis of the properties of these cells has begun to provide information on complex and significant biologic problems related to the cyclic AMP system.", "contents": "Studies of cyclic AMP action using mutant tissue culture cells. S49 mouse lymphoma cell mutants, each with a specific defect in its ability to generate or respond to cyclic AMP, have been isolated. Analysis of the properties of these cells has begun to provide information on complex and significant biologic problems related to the cyclic AMP system."}
{"id": "PMID:23990", "title": "[Correlation of growth-phase and streptodornase-production of beta-hemolytic streptococci group A (author's transl)].", "content": "77 M- and 48 T-typed strains of A-streptococci were compared with respect to their extinction, acidification and nuclease-production as a function of the growth-time. Strains of the same serotype (M 12) showed a change in the distribution of the isoenzymes of nucleases with respect to the growth-time. Half of the strains produced nuclease activity after 4 h. Streptodornase B was produced by all strains. With the growth the number of the nucleases found at the same time diminished, after 96 h in 70% of the strains the nuclease activity was represented by streptodornase B only.", "contents": "[Correlation of growth-phase and streptodornase-production of beta-hemolytic streptococci group A (author's transl)]. 77 M- and 48 T-typed strains of A-streptococci were compared with respect to their extinction, acidification and nuclease-production as a function of the growth-time. Strains of the same serotype (M 12) showed a change in the distribution of the isoenzymes of nucleases with respect to the growth-time. Half of the strains produced nuclease activity after 4 h. Streptodornase B was produced by all strains. With the growth the number of the nucleases found at the same time diminished, after 96 h in 70% of the strains the nuclease activity was represented by streptodornase B only."}
{"id": "PMID:23994", "title": "Depression of cell-mediated immunity following inoculation of Trichinella spiralis extract in the mouse.", "content": "Mice pretreated with Trichinella spiralis extract (TsE), or infected with the parasite, rejected primary skin allografts in 18-23 days and secondary allografts in 12-16 days. Mice pretreated with saline or with bovine serum albumin (BSA) rejected the primary allografts in 12-18 days and did not accept the secondary grafts. Inoculation of increasing doses of parental spleen cells from mice pretreated with saline or with BSA in F1 hybrids produced proportionately stronger graft-versus-host reactions (GvHR) whereas increasing doses of cells from TsE pretreated mice reduced proportionately the capacity of the inoculum to induce a GvHR. Immunodepression of the parental cells was obtained with 7 and with 4, but not with 2, daily injections of TsE. The depression waned rapidly after the treatment with TsE but a significant degree still remained after 3 days. Immunodepression by TsE cannot be solely explained by antigenic competition and although our results are consistent with the induction of suppressor cells, it is probable that other mechanisms are also involved.", "contents": "Depression of cell-mediated immunity following inoculation of Trichinella spiralis extract in the mouse. Mice pretreated with Trichinella spiralis extract (TsE), or infected with the parasite, rejected primary skin allografts in 18-23 days and secondary allografts in 12-16 days. Mice pretreated with saline or with bovine serum albumin (BSA) rejected the primary allografts in 12-18 days and did not accept the secondary grafts. Inoculation of increasing doses of parental spleen cells from mice pretreated with saline or with BSA in F1 hybrids produced proportionately stronger graft-versus-host reactions (GvHR) whereas increasing doses of cells from TsE pretreated mice reduced proportionately the capacity of the inoculum to induce a GvHR. Immunodepression of the parental cells was obtained with 7 and with 4, but not with 2, daily injections of TsE. The depression waned rapidly after the treatment with TsE but a significant degree still remained after 3 days. Immunodepression by TsE cannot be solely explained by antigenic competition and although our results are consistent with the induction of suppressor cells, it is probable that other mechanisms are also involved."}
{"id": "PMID:23995", "title": "Responses to polyvinyl pyrrolidone and pneumococcal polysaccharide in protein-deficient mice.", "content": "Indirect haemagglutination titres induced by polyvinyl pyrrolidone (PVP) or pneumococcal polysaccharide Type III (S111) were determined in mice maintained on a 4% albumin diet from weaning and normally-fed littermates. Responses to PVP, given intravenously (i.v.) or intraperitoneally (i.p.), were elevated by protein-deficiency at low antigen doses and increasingly depressed at high doses. Increases in the duration of protein-deficiency generally improved these responses. The persistence of tolerance was reduced by protein-deficiency and priming was evident in both groups when tolerance was broken. The low protein diet depressed responses to moderate doses of S111 given i.p. to C57Bl mice, but such responses were normal in BALB/c mice and in C57Bl mice injected i.v. High doses of S111 (i.p., i.v.) elicited poor responses in deficient mice. These findings are discussed in relation to previous studies using other antigens, with a view to elucidating mechanisms responsible for the effects of protein-deficiency.", "contents": "Responses to polyvinyl pyrrolidone and pneumococcal polysaccharide in protein-deficient mice. Indirect haemagglutination titres induced by polyvinyl pyrrolidone (PVP) or pneumococcal polysaccharide Type III (S111) were determined in mice maintained on a 4% albumin diet from weaning and normally-fed littermates. Responses to PVP, given intravenously (i.v.) or intraperitoneally (i.p.), were elevated by protein-deficiency at low antigen doses and increasingly depressed at high doses. Increases in the duration of protein-deficiency generally improved these responses. The persistence of tolerance was reduced by protein-deficiency and priming was evident in both groups when tolerance was broken. The low protein diet depressed responses to moderate doses of S111 given i.p. to C57Bl mice, but such responses were normal in BALB/c mice and in C57Bl mice injected i.v. High doses of S111 (i.p., i.v.) elicited poor responses in deficient mice. These findings are discussed in relation to previous studies using other antigens, with a view to elucidating mechanisms responsible for the effects of protein-deficiency."}
{"id": "PMID:23996", "title": "Restoration of suppressor function in athymic mice.", "content": "Antibody responses of normal and congenitally athymic (nu/nu) mice were measured to the phosphorylcholine determinant of a pneumococcal C-polysaccharide. The plaque-forming cell responses of athymic mice were approximately tenfold higher than for intact controls. This enhancement was equivalent to that obtained by treatment of controls with antithymocyte serum. In both cases, the enhanced responses presumably result from a lack of suppressor T cells. Reconstitution of athymic mice with normal thymocytes restored both suppressor and helper T cell functions. Whereas suppressor activity did not appear until 6 days after transplantation of T cells, helper activity was fully restored within 24 h and had diminished by 6 days.", "contents": "Restoration of suppressor function in athymic mice. Antibody responses of normal and congenitally athymic (nu/nu) mice were measured to the phosphorylcholine determinant of a pneumococcal C-polysaccharide. The plaque-forming cell responses of athymic mice were approximately tenfold higher than for intact controls. This enhancement was equivalent to that obtained by treatment of controls with antithymocyte serum. In both cases, the enhanced responses presumably result from a lack of suppressor T cells. Reconstitution of athymic mice with normal thymocytes restored both suppressor and helper T cell functions. Whereas suppressor activity did not appear until 6 days after transplantation of T cells, helper activity was fully restored within 24 h and had diminished by 6 days."}
{"id": "PMID:24000", "title": "Bactericidal activity of specific and azurophil granules from human neutrophils: studies with outer-membrane mutants of Salmonella typhimurium LT-2.", "content": "Extracts of specific granules and azurophil granules from human neutrophils were tested for their bactericidal activity against various lipopolysaccharide mutants of Salmonella typhimurium LT-2. Three purified granule populations, one specific and two azurophil, were obtained by isopycnic centrifugation of homogenized neutrophils. Each was extracted with 0.2 M acetate buffer (pH 4), and the extracts were dialyzed against phosphate-buffered saline (pH 7) to remove acetate. These extracts contained >/=84% of the lysozyme, lactoferrin, or myeloperoxidase initially present in the whole granules. The S. typhimurium mutants possessed Ra, Rc, Rd(1), Rd(2), or Re lipopolysaccharide. As the carbohydrate content of the lipopolysaccharide decreased, the bacteria became increasingly more susceptible to the bactericidal activity of all granule extracts. Bactericidal activity of the extracts was in the order: mixed (azurophil + specific) >/= azurophil >> specific. Specific granules were bacteriostatic for S through Rd(2) bacteria. They were bactericidal only for the Re mutant. Both azurophil granule populations were equally bactericidal. Extracts boiled for 30 min retained none of their bactericidal activity for any of the bacteria; however, they remained bacteriostatic for the deep rough (Rd(2), Re) mutants. Bactericidal activity was dependent upon pH, in that mixed and azurophil granule contents killed the smooth parent and Ra mutant best at pH 5, the Rc and Rd(1) mutants to the same degree at pH 5 to 8, and the deep rough mutants (Rd(2) and Re) best at pH 8. Specific granule contents were most bacteriostatic for S through Rd(2) bacteria at pH 5 and killed the Re mutant only at pH 8. Thus, as the S. typhimurium lipopolysaccharide content decreased, the bactericidal pH optimum increased. Killing by all extracts was dependent upon incubation temperature, with almost no bactericidal or bacteriostatic activity observed when bacteria and granule fractions were incubated on ice (2 degrees C) and plated immediately. Intermediate killing was observed at 22 degrees C. If bacteria were incubated with granule extracts at 2 degrees C, washed free of extract, suspended in medium without extract, and reincubated at 37 degrees C, killing was observed. This suggested that a component(s) of the extracts was sticking to the bacteria at 2 degrees C but killing only at 37 degrees C.", "contents": "Bactericidal activity of specific and azurophil granules from human neutrophils: studies with outer-membrane mutants of Salmonella typhimurium LT-2. Extracts of specific granules and azurophil granules from human neutrophils were tested for their bactericidal activity against various lipopolysaccharide mutants of Salmonella typhimurium LT-2. Three purified granule populations, one specific and two azurophil, were obtained by isopycnic centrifugation of homogenized neutrophils. Each was extracted with 0.2 M acetate buffer (pH 4), and the extracts were dialyzed against phosphate-buffered saline (pH 7) to remove acetate. These extracts contained >/=84% of the lysozyme, lactoferrin, or myeloperoxidase initially present in the whole granules. The S. typhimurium mutants possessed Ra, Rc, Rd(1), Rd(2), or Re lipopolysaccharide. As the carbohydrate content of the lipopolysaccharide decreased, the bacteria became increasingly more susceptible to the bactericidal activity of all granule extracts. Bactericidal activity of the extracts was in the order: mixed (azurophil + specific) >/= azurophil >> specific. Specific granules were bacteriostatic for S through Rd(2) bacteria. They were bactericidal only for the Re mutant. Both azurophil granule populations were equally bactericidal. Extracts boiled for 30 min retained none of their bactericidal activity for any of the bacteria; however, they remained bacteriostatic for the deep rough (Rd(2), Re) mutants. Bactericidal activity was dependent upon pH, in that mixed and azurophil granule contents killed the smooth parent and Ra mutant best at pH 5, the Rc and Rd(1) mutants to the same degree at pH 5 to 8, and the deep rough mutants (Rd(2) and Re) best at pH 8. Specific granule contents were most bacteriostatic for S through Rd(2) bacteria at pH 5 and killed the Re mutant only at pH 8. Thus, as the S. typhimurium lipopolysaccharide content decreased, the bactericidal pH optimum increased. Killing by all extracts was dependent upon incubation temperature, with almost no bactericidal or bacteriostatic activity observed when bacteria and granule fractions were incubated on ice (2 degrees C) and plated immediately. Intermediate killing was observed at 22 degrees C. If bacteria were incubated with granule extracts at 2 degrees C, washed free of extract, suspended in medium without extract, and reincubated at 37 degrees C, killing was observed. This suggested that a component(s) of the extracts was sticking to the bacteria at 2 degrees C but killing only at 37 degrees C."}
{"id": "PMID:24001", "title": "Role of complement in lethal bacterial lipopolysaccharide-induced hypotensive and coagulative changes.", "content": "The effect of C3 depletion on the multiple pathophysiological changes produced by a lethal dose of Serratia marcescens lipopolysaccharide (LPS) was evaluated. The injection of this LPS into rabbits resulted in biphasic hypotensive changes and thrombocytopenia. These changes were characterized by an acute, transient decrease occurring within minutes after injection followed by a second more gradual decrease beginning 30 to 60 min post-LPS. Prior depletion of C3, with the anticomplementary protein from cobra venom (CoF), did not alter the extent of either the gradual hypotensive and platelet changes or the coagulative and metabolic changes when normal and C3-depleted rabbits were compared. Importantly, the lethal effects of S. marcescens LPS were not reduced by prior depletion of C3. Only the immediate, reversible thrombocytopenia and hypotension were abrogated by C3 depletion.", "contents": "Role of complement in lethal bacterial lipopolysaccharide-induced hypotensive and coagulative changes. The effect of C3 depletion on the multiple pathophysiological changes produced by a lethal dose of Serratia marcescens lipopolysaccharide (LPS) was evaluated. The injection of this LPS into rabbits resulted in biphasic hypotensive changes and thrombocytopenia. These changes were characterized by an acute, transient decrease occurring within minutes after injection followed by a second more gradual decrease beginning 30 to 60 min post-LPS. Prior depletion of C3, with the anticomplementary protein from cobra venom (CoF), did not alter the extent of either the gradual hypotensive and platelet changes or the coagulative and metabolic changes when normal and C3-depleted rabbits were compared. Importantly, the lethal effects of S. marcescens LPS were not reduced by prior depletion of C3. Only the immediate, reversible thrombocytopenia and hypotension were abrogated by C3 depletion."}
{"id": "PMID:24002", "title": "Attachment of Bacteroides melaninogenicus subsp. asaccharolyticus to oral surfaces and its possible role in colonization of the mouth and of periodontal pockets.", "content": "This investigation examined the ability of cells of Bacteroides melaninogenicus subsp. asaccharolyticus 381 to adhere to surfaces that might be important for its initial colonization of the mouth and its subsequent colonization in periodontal pockets. Of 48 asaccharolytic strains of B. melaninogenicus, 47 agglutinated human erythrocytes, whereas none of 20 fermentative strains, which included reference cultures of the subspecies intermedius and melaninogenicus, were active. Electron microscopy indicated that both asaccharolytic and fermentative strains possessed pili; hence, the presence of pili did not correlate with the hemagglutinating activities of B. melaninogenicus strains. Both asaccharolytic and fermentative B. melaninogenicus strains suspended in phosphate-buffered saline adhered in high numbers to buccal epithelial cells and to the surfaces of several gram-positive bacteria tested, including Actinomyces viscosus, A. naeslundii, A. israelii, Streptococcus sanguis, and S. mitis. B. melaninogenicus subsp. asaccharolyticus 381 also attached, but in comparatively low numbers, to untreated and to saliva-treated hydroxyapatite. Addition of clarified whole saliva to suspensions of strain 381 almost completely eliminated adherence to buccal epithelial cells and to hydroxyapatite surfaces, but saliva had no detectable effect on attachment to gram-positive plaque bacteria. Both fermentative and nonfermentative strains of B. melaninogenicus also attached in high numbers to crevicular epithelial cells derived from human periodontal pockets, but normal human serum strongly inhibited attachment. Serum also inhibited attachment of strain 381 to saliva- and serum-treated hydroxyapatite, but it had little effect upon attachment to gram-positive bacteria. These observations suggested that salivary and serum components would strongly inhibit the attachment of B. melaninogenicus cells to several oral surfaces, but not to the surfaces of certain gram-positive bacteria commonly present in human dental plaque. This was confirmed by an in vivo experiment in which streptomycin-labeled cells of B. melaninogenicus 381-R were introduced into the mouths of two volunteers. After 10 min, several hundred-fold higher numbers of the organism were recovered from preformed bacterial plaque present on teeth than from clean tooth surfaces or from the buccal mucosa and tongue dorsum. High numbers of B. melaninogenicus cells were also recovered from preformed plaque after 150 min, but virtually no cells of the organism were recovered from the other surfaces studied. These data suggest that the presence of dental plaque containing Actinomyces and other gram-positive bacteria may be essential for the attachment and colonization of B. melaninogenicus cells after their initial introduction into the mouth. Similarly, the presence of subgingival plaque containing gram-positive bacteria may be necessary for its secondary colonization in periodontal pockets.", "contents": "Attachment of Bacteroides melaninogenicus subsp. asaccharolyticus to oral surfaces and its possible role in colonization of the mouth and of periodontal pockets. This investigation examined the ability of cells of Bacteroides melaninogenicus subsp. asaccharolyticus 381 to adhere to surfaces that might be important for its initial colonization of the mouth and its subsequent colonization in periodontal pockets. Of 48 asaccharolytic strains of B. melaninogenicus, 47 agglutinated human erythrocytes, whereas none of 20 fermentative strains, which included reference cultures of the subspecies intermedius and melaninogenicus, were active. Electron microscopy indicated that both asaccharolytic and fermentative strains possessed pili; hence, the presence of pili did not correlate with the hemagglutinating activities of B. melaninogenicus strains. Both asaccharolytic and fermentative B. melaninogenicus strains suspended in phosphate-buffered saline adhered in high numbers to buccal epithelial cells and to the surfaces of several gram-positive bacteria tested, including Actinomyces viscosus, A. naeslundii, A. israelii, Streptococcus sanguis, and S. mitis. B. melaninogenicus subsp. asaccharolyticus 381 also attached, but in comparatively low numbers, to untreated and to saliva-treated hydroxyapatite. Addition of clarified whole saliva to suspensions of strain 381 almost completely eliminated adherence to buccal epithelial cells and to hydroxyapatite surfaces, but saliva had no detectable effect on attachment to gram-positive plaque bacteria. Both fermentative and nonfermentative strains of B. melaninogenicus also attached in high numbers to crevicular epithelial cells derived from human periodontal pockets, but normal human serum strongly inhibited attachment. Serum also inhibited attachment of strain 381 to saliva- and serum-treated hydroxyapatite, but it had little effect upon attachment to gram-positive bacteria. These observations suggested that salivary and serum components would strongly inhibit the attachment of B. melaninogenicus cells to several oral surfaces, but not to the surfaces of certain gram-positive bacteria commonly present in human dental plaque. This was confirmed by an in vivo experiment in which streptomycin-labeled cells of B. melaninogenicus 381-R were introduced into the mouths of two volunteers. After 10 min, several hundred-fold higher numbers of the organism were recovered from preformed bacterial plaque present on teeth than from clean tooth surfaces or from the buccal mucosa and tongue dorsum. High numbers of B. melaninogenicus cells were also recovered from preformed plaque after 150 min, but virtually no cells of the organism were recovered from the other surfaces studied. These data suggest that the presence of dental plaque containing Actinomyces and other gram-positive bacteria may be essential for the attachment and colonization of B. melaninogenicus cells after their initial introduction into the mouth. Similarly, the presence of subgingival plaque containing gram-positive bacteria may be necessary for its secondary colonization in periodontal pockets."}
{"id": "PMID:24004", "title": "Adoptive immunochemotherapy of a transplantable AKR leukemia (K36).", "content": "Adoptive immunotherapy of a transplantable AKR leukemia (K36) was carried out as an adjunct to cytoxan chemotherapy using normal allogeneic H-2-incompatible spleen cells as well as sensitized H-2-matched allogeneic spleen cells. A significant therapeutic effect was obtained with cytoxan and allogeneic C57BL/6 splenocytes, demonstrating the potential use of the graft-versus-host reaction. Utilizing specific adoptive immunochemotherapy, a maximum effect was found with splenocytes from allogeneic but H-2-compatible CBA/J mice immunized against an allogeneic Gross-virus-induced lymphoma (E female G2). This therapeutic effect was most likely the result of prior sensitization of donor lymphocytes to common virus-associated tumor antigens.", "contents": "Adoptive immunochemotherapy of a transplantable AKR leukemia (K36). Adoptive immunotherapy of a transplantable AKR leukemia (K36) was carried out as an adjunct to cytoxan chemotherapy using normal allogeneic H-2-incompatible spleen cells as well as sensitized H-2-matched allogeneic spleen cells. A significant therapeutic effect was obtained with cytoxan and allogeneic C57BL/6 splenocytes, demonstrating the potential use of the graft-versus-host reaction. Utilizing specific adoptive immunochemotherapy, a maximum effect was found with splenocytes from allogeneic but H-2-compatible CBA/J mice immunized against an allogeneic Gross-virus-induced lymphoma (E female G2). This therapeutic effect was most likely the result of prior sensitization of donor lymphocytes to common virus-associated tumor antigens."}
{"id": "PMID:24008", "title": "Sperm-freezing and donor insemination.", "content": "A comparison between freezing of human sperm using glycerol or glycerol egg-yolk citrate is presented. Freezing was performed with a gradual lowering of the temperature using alchol-liquid nitrogen or by immersion into liquid nitrogen. Great variations were observed within the same donor sperm sample when the sperm was frozen according to different techniques and marked post-thaw, motility variations were also found between spermatozoa from different donors. No statistically significant differences were found in the number of pregnancies obtained following inseminations with sperm frozen according to the two methods.", "contents": "Sperm-freezing and donor insemination. A comparison between freezing of human sperm using glycerol or glycerol egg-yolk citrate is presented. Freezing was performed with a gradual lowering of the temperature using alchol-liquid nitrogen or by immersion into liquid nitrogen. Great variations were observed within the same donor sperm sample when the sperm was frozen according to different techniques and marked post-thaw, motility variations were also found between spermatozoa from different donors. No statistically significant differences were found in the number of pregnancies obtained following inseminations with sperm frozen according to the two methods."}
{"id": "PMID:24009", "title": "Electrochemical effects of metals on IUDs.", "content": "Electrochemical effects within the uterus are being studied, particularly as they pertain to IUDs made in total or in part of metals. The intrauterine potential as measured with either metal or nonpolarizable salt electrodes is positive at the fundal with respect to the cervical end of the uterus. Placement of dissimilar metal electrodes within the uterus will induce voltage gradients that are roughly predictable from their cell potential in blood as an electrolyte. When copper and zinc electrodes are placed at opposite ends of the uterus, they induce voltage gradients that are typically greater than 100 mv per cm. External copper and zinc wires connected at one end, and with the other ends in contact with various positions on the skin of rats, were found to influence potential gradients within the uterus. When a length of zinc wire was wound around the upper portion of the stem of a small Cu-7 200 IUD, it took about 1 year from insertion for the zinc to disappear. When the zinc wire was wound around the lower portion of the stem, it disappeared in 1 month. The zinc reduced intrauterine corrosion of the copper and it was more effective at reducing copper corrosion when in the lower stem position.", "contents": "Electrochemical effects of metals on IUDs. Electrochemical effects within the uterus are being studied, particularly as they pertain to IUDs made in total or in part of metals. The intrauterine potential as measured with either metal or nonpolarizable salt electrodes is positive at the fundal with respect to the cervical end of the uterus. Placement of dissimilar metal electrodes within the uterus will induce voltage gradients that are roughly predictable from their cell potential in blood as an electrolyte. When copper and zinc electrodes are placed at opposite ends of the uterus, they induce voltage gradients that are typically greater than 100 mv per cm. External copper and zinc wires connected at one end, and with the other ends in contact with various positions on the skin of rats, were found to influence potential gradients within the uterus. When a length of zinc wire was wound around the upper portion of the stem of a small Cu-7 200 IUD, it took about 1 year from insertion for the zinc to disappear. When the zinc wire was wound around the lower portion of the stem, it disappeared in 1 month. The zinc reduced intrauterine corrosion of the copper and it was more effective at reducing copper corrosion when in the lower stem position."}
{"id": "PMID:24010", "title": "Antigens from human seminal plasma. Part III: studies on two new antigens from the tricholoracetic acid soluble fraction.", "content": "Two new antigens were isolated from the trichloroacetic acid soluble fraction of human seminal plasma: a polysaccharide (G-3) and a glycopeptide (G-4). Both were homogeneous, and hand sedimentation constants at infinite dilution of 2.9 X 10(-13) and 2.0 X 10(-13) resectively. Chemical and physicochemical studies suggest that both are branched molecules composed mainly of alpha-D-glucopyranosidic residues. The peptide component of G-R contains a high proporiton of the basic amino acids arginine and lysine. Since both antigens are polydispered, the low percentage of sialic acids or of some amino acids determined might have antigenic significance.", "contents": "Antigens from human seminal plasma. Part III: studies on two new antigens from the tricholoracetic acid soluble fraction. Two new antigens were isolated from the trichloroacetic acid soluble fraction of human seminal plasma: a polysaccharide (G-3) and a glycopeptide (G-4). Both were homogeneous, and hand sedimentation constants at infinite dilution of 2.9 X 10(-13) and 2.0 X 10(-13) resectively. Chemical and physicochemical studies suggest that both are branched molecules composed mainly of alpha-D-glucopyranosidic residues. The peptide component of G-R contains a high proporiton of the basic amino acids arginine and lysine. Since both antigens are polydispered, the low percentage of sialic acids or of some amino acids determined might have antigenic significance."}
{"id": "PMID:24011", "title": "Augmentative effect of ascorbic acid upon induction of human ovulation in clomiphene-ineffective anovulatory women.", "content": "The effect of the administration of 1-ascorbic acid, either alone or combined with clomiphene, upon induction of human ovulation was investigated in clomiphene-inffective anovulatory women. Oral administration of daily 400 mg of ascorbic acid induced ovulation in two out of five habitually anovulatory cycles and in one out of eight first-grade amenorrhea cases, and was ineffective in all six second-grade hypothalamic amenorrhea cases. Combined administration of ascorbic acid with 5 days of clomiphene induced ovulation in five out of five habitually anovulatory cycles, in 10 out of 17 first-grade hypothalamic amenorrhea cases, and in two out of nine second-grade hypothalamic amenorrhea cases. Pregnancy was established in eight out of 18 sterile, habitually-anovulatory or first-grade amenorrheic women with the combined ascorbic acid-clomiphene therapy, and in one out of five sterile, habitually anovulatory women with ascorbic acid therapy alone. Since administration of ascorbic acid induced no changed in blood FSH, LH, and amount of cervical mucus, and it is well established that LH decreases dose-dependency of the ascorbic acid content in the rat ovaries, the possible site of action of ascorbic acid seems to be at the ovarian level.", "contents": "Augmentative effect of ascorbic acid upon induction of human ovulation in clomiphene-ineffective anovulatory women. The effect of the administration of 1-ascorbic acid, either alone or combined with clomiphene, upon induction of human ovulation was investigated in clomiphene-inffective anovulatory women. Oral administration of daily 400 mg of ascorbic acid induced ovulation in two out of five habitually anovulatory cycles and in one out of eight first-grade amenorrhea cases, and was ineffective in all six second-grade hypothalamic amenorrhea cases. Combined administration of ascorbic acid with 5 days of clomiphene induced ovulation in five out of five habitually anovulatory cycles, in 10 out of 17 first-grade hypothalamic amenorrhea cases, and in two out of nine second-grade hypothalamic amenorrhea cases. Pregnancy was established in eight out of 18 sterile, habitually-anovulatory or first-grade amenorrheic women with the combined ascorbic acid-clomiphene therapy, and in one out of five sterile, habitually anovulatory women with ascorbic acid therapy alone. Since administration of ascorbic acid induced no changed in blood FSH, LH, and amount of cervical mucus, and it is well established that LH decreases dose-dependency of the ascorbic acid content in the rat ovaries, the possible site of action of ascorbic acid seems to be at the ovarian level."}
{"id": "PMID:24012", "title": "Varicocele: relation between anoxia and hypospermatogenesis.", "content": "Three groups of patients were analysed: varicocele patients with abnormal seminal fluid (17 cases), variococele and normal sperm (seven cases) and normal males (17 cases). Blood gas was secured in the internal spermatic vein, perpheric vein and femural artery, in an attempt to evaluate the possibility of altered gas content as a cause of spermatogenic depression. No statistical differences were found when we compared the three groups. We concluded that anoxia was not the cause of hypospermatogenesis in varicocele patients.", "contents": "Varicocele: relation between anoxia and hypospermatogenesis. Three groups of patients were analysed: varicocele patients with abnormal seminal fluid (17 cases), variococele and normal sperm (seven cases) and normal males (17 cases). Blood gas was secured in the internal spermatic vein, perpheric vein and femural artery, in an attempt to evaluate the possibility of altered gas content as a cause of spermatogenic depression. No statistical differences were found when we compared the three groups. We concluded that anoxia was not the cause of hypospermatogenesis in varicocele patients."}
{"id": "PMID:24013", "title": "A morphological and physiological study of mesotubarium ovarica in humans.", "content": "In order to clarify the mechanisms by which the egg is transported from the ruptured follicle into the fimbrial end of the Fallopian tube in the human being, the mesotubarium ovarica (MTO), the unique anatomical structure which connects the tubal fimbriae and the ovary, was studied in seven human adnexal specimens histochemically and electron microscopically. The results demonstrated clearly the presence of smooth muscle cells in the MTO, and failed to demonstrate the presence of cilia in the lining epithelial cells of the MTO. Based on these morphological results, contractility of the MTO was studied in vitro by using a muscle chamber and a pressure transducer with 26 human adnexal specimens. Spontaneous contractile activites of regular frequency and moderate intensity were observed in the MTOs of all specimens examined. A possible role of the MTO in the mechanisms of ovum pickup at the time of ovulation is discussed.", "contents": "A morphological and physiological study of mesotubarium ovarica in humans. In order to clarify the mechanisms by which the egg is transported from the ruptured follicle into the fimbrial end of the Fallopian tube in the human being, the mesotubarium ovarica (MTO), the unique anatomical structure which connects the tubal fimbriae and the ovary, was studied in seven human adnexal specimens histochemically and electron microscopically. The results demonstrated clearly the presence of smooth muscle cells in the MTO, and failed to demonstrate the presence of cilia in the lining epithelial cells of the MTO. Based on these morphological results, contractility of the MTO was studied in vitro by using a muscle chamber and a pressure transducer with 26 human adnexal specimens. Spontaneous contractile activites of regular frequency and moderate intensity were observed in the MTOs of all specimens examined. A possible role of the MTO in the mechanisms of ovum pickup at the time of ovulation is discussed."}
{"id": "PMID:24014", "title": "Postnidatory effects of luteinizing hormone releasing hormone (LHRH) in hamsters.", "content": "Whereas the administration of LHRH to pregnant hamsters has no effect during the prenidatory period, the hormone is effective in terminating pregnancy when given after implantation (days 6-10). The ED50 for pregnancy termination over this period approximates a dose of 0.35-0.4 mg b.i.d. When given to pregnant females in a second study, the effects of LHRH at this dose were completely reverse by minute doses of progesterone (30 microgram and above). Finally, administration of LHRH at 1.5 mg b.i.d., from days 6-10 was followed by daily sacrifice through day 12; bloods were sampled at autopsy for progesterone evaluation. Autopsies on days 7 and 8 showed few differences between controls and LHRH-treated hamsters, although decreased weights of the uterine/conceptus units signaled the initation of resorption. Significant LHRH-induced decreases in circulating progesterone were seen by day 9. Fetal resorption continued and was essentially complete by day 11, while progesterone levels continued depressed through the end of the study.", "contents": "Postnidatory effects of luteinizing hormone releasing hormone (LHRH) in hamsters. Whereas the administration of LHRH to pregnant hamsters has no effect during the prenidatory period, the hormone is effective in terminating pregnancy when given after implantation (days 6-10). The ED50 for pregnancy termination over this period approximates a dose of 0.35-0.4 mg b.i.d. When given to pregnant females in a second study, the effects of LHRH at this dose were completely reverse by minute doses of progesterone (30 microgram and above). Finally, administration of LHRH at 1.5 mg b.i.d., from days 6-10 was followed by daily sacrifice through day 12; bloods were sampled at autopsy for progesterone evaluation. Autopsies on days 7 and 8 showed few differences between controls and LHRH-treated hamsters, although decreased weights of the uterine/conceptus units signaled the initation of resorption. Significant LHRH-induced decreases in circulating progesterone were seen by day 9. Fetal resorption continued and was essentially complete by day 11, while progesterone levels continued depressed through the end of the study."}
{"id": "PMID:24015", "title": "Vascular changes in traumatic amenorrhea and hypomenorrhea.", "content": "Pelvic angiography was performed in 12 cases of amenorrhea and hypomenorrhea which developed following curettage of abortion and in the puerperium. Six cases of similar age and obstetric history with normal menstrual cycles served as control. Pelvic angiography revealed widespread vascular occlusion of myometrial arteries, in seven of the twelve cases. These findings account for the small amount of endometrium removed on diagnostic curettage in these cases as well as the greatly reduced menstrual loss. The poor obstetric history of the cases studied may well be due to this excessive vascular damage.", "contents": "Vascular changes in traumatic amenorrhea and hypomenorrhea. Pelvic angiography was performed in 12 cases of amenorrhea and hypomenorrhea which developed following curettage of abortion and in the puerperium. Six cases of similar age and obstetric history with normal menstrual cycles served as control. Pelvic angiography revealed widespread vascular occlusion of myometrial arteries, in seven of the twelve cases. These findings account for the small amount of endometrium removed on diagnostic curettage in these cases as well as the greatly reduced menstrual loss. The poor obstetric history of the cases studied may well be due to this excessive vascular damage."}
{"id": "PMID:24016", "title": "Quenching of tryptophan fluorescence in human antithrombin III by iodide ion.", "content": "Iodide is an efficient quencher of antithrombin III intrinsic tryptophan fluorescence. The quenching pattern indicates that about 60% of the tryptophyl fluorescence originates from exposed residues in the multitryptophan-containing protein. In denaturing media all of the tryptophyls are solvent-exposed. The binding of heparin to antithrombin III influences the number of solvent-exposed tryptophan residues. By studying the dependence of the quenching on pH, information regarding the presence of charged residues adjacent to tryptophyls was obtained.", "contents": "Quenching of tryptophan fluorescence in human antithrombin III by iodide ion. Iodide is an efficient quencher of antithrombin III intrinsic tryptophan fluorescence. The quenching pattern indicates that about 60% of the tryptophyl fluorescence originates from exposed residues in the multitryptophan-containing protein. In denaturing media all of the tryptophyls are solvent-exposed. The binding of heparin to antithrombin III influences the number of solvent-exposed tryptophan residues. By studying the dependence of the quenching on pH, information regarding the presence of charged residues adjacent to tryptophyls was obtained."}
{"id": "PMID:24017", "title": "Photochemical evidence for the presence of histidyl residue in the active site of alkaline mesentericopeptidase.", "content": "The photosensitized oxidation of alkaline mesentericopeptidase in the presence of methylene blue results in a first-order rate of inactivation. The loss of enzymatic activity towards casein and N-acetyl-L-tyrosine ethyl ester closely correlates with the destruction of one histidyl residue. A pK value of 6.8 is determined from the sigmoid pH-dependence of the photoinactivation rate. This suggests the involvement of a normal titrating imidazole group in the active site of mesentericopeptidase. The competitive inhibitor Na-benzoyl-L-arginine protects the enzyme from photoinactivation. A conclusion is made that the active site histidyl residue is modified. Circular dichroism spectra show no change in the protein conformation during the photodynamic treatment.", "contents": "Photochemical evidence for the presence of histidyl residue in the active site of alkaline mesentericopeptidase. The photosensitized oxidation of alkaline mesentericopeptidase in the presence of methylene blue results in a first-order rate of inactivation. The loss of enzymatic activity towards casein and N-acetyl-L-tyrosine ethyl ester closely correlates with the destruction of one histidyl residue. A pK value of 6.8 is determined from the sigmoid pH-dependence of the photoinactivation rate. This suggests the involvement of a normal titrating imidazole group in the active site of mesentericopeptidase. The competitive inhibitor Na-benzoyl-L-arginine protects the enzyme from photoinactivation. A conclusion is made that the active site histidyl residue is modified. Circular dichroism spectra show no change in the protein conformation during the photodynamic treatment."}
{"id": "PMID:24018", "title": "The peripheral and central neural actions of clonidine in normal and glaucomatous eyes.", "content": "The peripheral and central neural actions of clonidine on normal and glaucomatous eyes have been investigated. Threshold doses of clonidine applied topically induced a monotonic decrease of intraocular pressure in the treated eye and had no effect on the contralateral eye. With increased clonidine dose, a decrease of intraocular pressure occurred in the untreated eye, and there was a concomitant decrease of systemic arterial blood pressure. Analysis of aqueous humor dynamics showed that the ocular response to the peripheral and the central neural actions of clonidine were without effect on the tonographic coefficient of outflow facility. The episcleral venous pressure decreased in both the treated and the untreated eyes, but the changes were too small to account for the observed decrease of intraocular pressure. The results are consistent with the concept that both the peripheral and central ocular hypotensive actions of clonidine are mediated by an inhibition of adrenergic neurogenic vasoconstriction in the eye.", "contents": "The peripheral and central neural actions of clonidine in normal and glaucomatous eyes. The peripheral and central neural actions of clonidine on normal and glaucomatous eyes have been investigated. Threshold doses of clonidine applied topically induced a monotonic decrease of intraocular pressure in the treated eye and had no effect on the contralateral eye. With increased clonidine dose, a decrease of intraocular pressure occurred in the untreated eye, and there was a concomitant decrease of systemic arterial blood pressure. Analysis of aqueous humor dynamics showed that the ocular response to the peripheral and the central neural actions of clonidine were without effect on the tonographic coefficient of outflow facility. The episcleral venous pressure decreased in both the treated and the untreated eyes, but the changes were too small to account for the observed decrease of intraocular pressure. The results are consistent with the concept that both the peripheral and central ocular hypotensive actions of clonidine are mediated by an inhibition of adrenergic neurogenic vasoconstriction in the eye."}
{"id": "PMID:24019", "title": "Reappraisal of the sympathetic role in the sphincteric urethra. Denervation supersensitivity of the urethra of the chronic neurogenic bladder to alpha-adrenergic drugs.", "content": "The response of urethral pressure to administration of an alpha-stimulant was compared between a group of eight patients with chronic neurogenic bladders as evidenced by positive denervation supersensitivity to parasympathomimetic bethanechol chloride and a group of ten control patients. A supersensitive response to administration of an alpha-stimulant with a rise of maximum urethral pressure, 10 mm Hg or more above the control urethral pressure, was uniformly observed in the urethra of patients with chronically denervated bladders. Our results appear to add pharmacologic evidence of alpha-adrenergic predominance over the parasympathetic in the urethra which is believed to be innervated dually in the recently envolving new concept.", "contents": "Reappraisal of the sympathetic role in the sphincteric urethra. Denervation supersensitivity of the urethra of the chronic neurogenic bladder to alpha-adrenergic drugs. The response of urethral pressure to administration of an alpha-stimulant was compared between a group of eight patients with chronic neurogenic bladders as evidenced by positive denervation supersensitivity to parasympathomimetic bethanechol chloride and a group of ten control patients. A supersensitive response to administration of an alpha-stimulant with a rise of maximum urethral pressure, 10 mm Hg or more above the control urethral pressure, was uniformly observed in the urethra of patients with chronically denervated bladders. Our results appear to add pharmacologic evidence of alpha-adrenergic predominance over the parasympathetic in the urethra which is believed to be innervated dually in the recently envolving new concept."}
{"id": "PMID:24021", "title": "[Endocrine active pancreatic neoplasms].", "content": "The tumor-forming endocrine cells of the pancreas belong to the APUD system. These cells are of neuroectodermal origin. The tumor can be diagnosed in most cases by a distinct clinical picture, and the diagnosis can be veryfied by direct hormone determination or/and by the biochemical disorders caused by the hormones. For localisation angiography, szintigrams, endoscopic pancreatography, and sonograms were used up to now without convincing results in many cases; computerized tomography promises to be the decisive examination in the future. Three hormones can, up to now, not yet be correlated with a distinct clinical picture specific for a pancreatic tumor. On the other hand, four tumors are responsible for a very typical clinical entity, the insulinoma, the glucagonoma, the gastrinoma, and the vipoma, as illustrated by our own cases. The surgical therapy consists mainly in enucleation of an adenoma or in partial pancreatic resection. Total pancreatectomy is indicated only in few cases. The Zollinger-Ellison syndrome is treated best by total gastrectomy. Malignant tumors are sensible to streptozotozin.", "contents": "[Endocrine active pancreatic neoplasms]. The tumor-forming endocrine cells of the pancreas belong to the APUD system. These cells are of neuroectodermal origin. The tumor can be diagnosed in most cases by a distinct clinical picture, and the diagnosis can be veryfied by direct hormone determination or/and by the biochemical disorders caused by the hormones. For localisation angiography, szintigrams, endoscopic pancreatography, and sonograms were used up to now without convincing results in many cases; computerized tomography promises to be the decisive examination in the future. Three hormones can, up to now, not yet be correlated with a distinct clinical picture specific for a pancreatic tumor. On the other hand, four tumors are responsible for a very typical clinical entity, the insulinoma, the glucagonoma, the gastrinoma, and the vipoma, as illustrated by our own cases. The surgical therapy consists mainly in enucleation of an adenoma or in partial pancreatic resection. Total pancreatectomy is indicated only in few cases. The Zollinger-Ellison syndrome is treated best by total gastrectomy. Malignant tumors are sensible to streptozotozin."}
{"id": "PMID:24022", "title": "Hemoglobin Lufkin: beta 29 (B11) Gly replaced by Asp. An unstable hemoglobin variant involving an internal amino acid residue.", "content": "Hemoglobin Lufkin was found in a Black-American family. Structural analysis of the abnormal hemoglobin indicates a substitution of aspartic acid for glycine at position 29 in the beta chain. Marked instability of the variant hemoglobin is demonstrated by the rapid formation of inclusion bodies upon exposure of the red cells to redox dyes and by the large percentage of precipitated hemoglobin at 65 degrees C. The oxygen affinity, the Bohr effect, and the degree of cooperativity of Hb Lufkin and Hb A are similar over the physiologic pH range. However, at acid pH the oxygen affinity of the variant is increased. Unlike several other reported variants in the B helix, Hb Lufkin is not associated with methemoglobinemia.", "contents": "Hemoglobin Lufkin: beta 29 (B11) Gly replaced by Asp. An unstable hemoglobin variant involving an internal amino acid residue. Hemoglobin Lufkin was found in a Black-American family. Structural analysis of the abnormal hemoglobin indicates a substitution of aspartic acid for glycine at position 29 in the beta chain. Marked instability of the variant hemoglobin is demonstrated by the rapid formation of inclusion bodies upon exposure of the red cells to redox dyes and by the large percentage of precipitated hemoglobin at 65 degrees C. The oxygen affinity, the Bohr effect, and the degree of cooperativity of Hb Lufkin and Hb A are similar over the physiologic pH range. However, at acid pH the oxygen affinity of the variant is increased. Unlike several other reported variants in the B helix, Hb Lufkin is not associated with methemoglobinemia."}
{"id": "PMID:24030", "title": "Contribution of a net transmembrane HCO3- flux to intracellular acid-base regulation.", "content": "Experiments were performed to determine the relative effects of a net extracellular-to-intracellular HCO3- flux and of elevated carbon dioxide tension (PCO2) on cellular acid-base regulation. Isolated rabbit hearts were perfused by recirculating a small volume of Ringer solution in which the PCO2 and the HCO3- concentration could be independently altered. Net HCO3- flux was assessed by the disappearance of HCO3- from perfusate. Between 40 and 100 Torr PCO2, a HCO3- flux into the cell occurs only when perfusate HCO3- concentration is increased. Therefore, by selective manipulation of perfusate HCO3- and PCO2 it is possible to induce hypercapnia with or without an accompanying HCO3- flux. When perfusate HCO3- concentration was increased from 20 to 36 mM, cellular HCO3- concentration increased from 22.5 +/- 0.8 to 26.1 +/- 1.0 mM at 40 Torr PCO2 and from 27.8 +/- 0.7 to 34.1 +/- 1.4 mM at 98 Torr PCO2. These increases can be accounted for by the amount of HCO3- that disappeared from the perfusate. The results suggest that most of the initial cell CO2 buffering is provided by the net HCO3- flux in addition to the passive physicochemical buffering.", "contents": "Contribution of a net transmembrane HCO3- flux to intracellular acid-base regulation. Experiments were performed to determine the relative effects of a net extracellular-to-intracellular HCO3- flux and of elevated carbon dioxide tension (PCO2) on cellular acid-base regulation. Isolated rabbit hearts were perfused by recirculating a small volume of Ringer solution in which the PCO2 and the HCO3- concentration could be independently altered. Net HCO3- flux was assessed by the disappearance of HCO3- from perfusate. Between 40 and 100 Torr PCO2, a HCO3- flux into the cell occurs only when perfusate HCO3- concentration is increased. Therefore, by selective manipulation of perfusate HCO3- and PCO2 it is possible to induce hypercapnia with or without an accompanying HCO3- flux. When perfusate HCO3- concentration was increased from 20 to 36 mM, cellular HCO3- concentration increased from 22.5 +/- 0.8 to 26.1 +/- 1.0 mM at 40 Torr PCO2 and from 27.8 +/- 0.7 to 34.1 +/- 1.4 mM at 98 Torr PCO2. These increases can be accounted for by the amount of HCO3- that disappeared from the perfusate. The results suggest that most of the initial cell CO2 buffering is provided by the net HCO3- flux in addition to the passive physicochemical buffering."}
{"id": "PMID:24031", "title": "Effect of pH on cardiorespiratory and metabolic responses to exercise.", "content": "Five male subjects performed exercise at 33, 66, and 95% of their maximum power output on three occasions in random order. Each study was preceded by a 3-h period in which capsules were taken by mouth, containing either CaCO3 (control, NH4Cl (acidosis), or NaHCO3 (alkalosis) in a dose of 0.3 g/kg body wt; preexercise blood pH was 7.38 +/- 0.015, 7.21 +/- 0.033, and 7.43 +/- 0.029, respectively. Exercise was continuous and maintained for 20 min at the two lower power outputs and for as long as possible at the highest. Compared with control (270 +/- 13 s), endurance time at the highest power output was reduced in acidosis (160 +/- 22 s) and increased in alkalosis (438 +/- 120 s). No differences were observed for central cardiovascular changes in exercise (cardiac output, frequency, or stroke volume). The respiratory changes expected from changes in blood pH were observed, with a higher alveolar ventilation in acidosis. At all power outputs arterialized venous lactate was lowest in acidosis and highest in alkalosis. Plasma glycerol and free fatty acids were lowest in acidosis. Changes in blood [HCO3-] and pH were shown to have major effects on metabolism in exercise which presumably were responsible for impaired endurance.", "contents": "Effect of pH on cardiorespiratory and metabolic responses to exercise. Five male subjects performed exercise at 33, 66, and 95% of their maximum power output on three occasions in random order. Each study was preceded by a 3-h period in which capsules were taken by mouth, containing either CaCO3 (control, NH4Cl (acidosis), or NaHCO3 (alkalosis) in a dose of 0.3 g/kg body wt; preexercise blood pH was 7.38 +/- 0.015, 7.21 +/- 0.033, and 7.43 +/- 0.029, respectively. Exercise was continuous and maintained for 20 min at the two lower power outputs and for as long as possible at the highest. Compared with control (270 +/- 13 s), endurance time at the highest power output was reduced in acidosis (160 +/- 22 s) and increased in alkalosis (438 +/- 120 s). No differences were observed for central cardiovascular changes in exercise (cardiac output, frequency, or stroke volume). The respiratory changes expected from changes in blood pH were observed, with a higher alveolar ventilation in acidosis. At all power outputs arterialized venous lactate was lowest in acidosis and highest in alkalosis. Plasma glycerol and free fatty acids were lowest in acidosis. Changes in blood [HCO3-] and pH were shown to have major effects on metabolism in exercise which presumably were responsible for impaired endurance."}
{"id": "PMID:24032", "title": "Catecholamine-synthesizing enzymes in adrenals of seasonally acclimatized voles.", "content": "Tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities were assayed in adrenal glands of the following groups of the Alaskan red-backed vole (Clethrionomys rutilus dawsoni): 1) laboratory reared at 20 degrees C and 2) exposed to 5 degrees C for 1, 3, 7, and 28 days; 3) wild, summer acclimatized; 4) wild, fall acclimatized; and 5) wild, winter acclimatized. TH activity in laboratory-acclimated voles exposed to 5 degrees C was increased by 2 times after 3 days and remained elevated after 28 days. PNMT activity in these same voles was increased after 7 days and also remained elevated after 28 days of cold exposure. In wild-acclimatized voles TH activity and PNMT activity in summer were equivalent to levels in 28-day cold-acclimated laboratory voles. In fall, TH activity was increased to 2.5 times the summer value. It decreased by midwinter, but remained elevated above the summer level. In contrast, PNMT activity appeared unchanged from summer through fall and winter. Pregnant summer voles had markedly increased TH activity. Adrenal norepinephrine and epinephrine did not change significantly with cold acclimation or seasonal acclimatization. Thus, acclimatization of wild voles to fall and winter conditions involved aquisition of a greater capacity to synthesize adrenal catecholamines than that produced by exposing laboratory-reared voles to an extended period of cold.", "contents": "Catecholamine-synthesizing enzymes in adrenals of seasonally acclimatized voles. Tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities were assayed in adrenal glands of the following groups of the Alaskan red-backed vole (Clethrionomys rutilus dawsoni): 1) laboratory reared at 20 degrees C and 2) exposed to 5 degrees C for 1, 3, 7, and 28 days; 3) wild, summer acclimatized; 4) wild, fall acclimatized; and 5) wild, winter acclimatized. TH activity in laboratory-acclimated voles exposed to 5 degrees C was increased by 2 times after 3 days and remained elevated after 28 days. PNMT activity in these same voles was increased after 7 days and also remained elevated after 28 days of cold exposure. In wild-acclimatized voles TH activity and PNMT activity in summer were equivalent to levels in 28-day cold-acclimated laboratory voles. In fall, TH activity was increased to 2.5 times the summer value. It decreased by midwinter, but remained elevated above the summer level. In contrast, PNMT activity appeared unchanged from summer through fall and winter. Pregnant summer voles had markedly increased TH activity. Adrenal norepinephrine and epinephrine did not change significantly with cold acclimation or seasonal acclimatization. Thus, acclimatization of wild voles to fall and winter conditions involved aquisition of a greater capacity to synthesize adrenal catecholamines than that produced by exposing laboratory-reared voles to an extended period of cold."}
{"id": "PMID:24033", "title": "A32390A, a new biologically active metabolite. I. Discovery and fermentation studies.", "content": "A32390A is an isonitrile-containing derivative of diacyl D-mannitol. The compound is produced in fermentation as the major component of a metabolic complex known as A32390. A32390A inhibits dopamine-beta-hydroxylase reduces heart and adrenal norepinephrine levels, lowers blood pressure in hypertensive rats, and possesses antibiotic activity vs. Gram-positive bacteria and fungi, including Candida albicans. A32390 is produced in submerged culture by a mold, a species of Pyrenochaeta, NRRL-5786. Glucose and sucrose are among the best carbon sources for the biosynthesis of A32390. Mannitol, although a substituent of the A32390A molecule, supports little or no biosynthesis of the compound when employed as the major carbon source for the fermentation. The addition of crotonic acid derivatives. ethanol, or L-histidine to the fermentation medium enhances the level of A32390 produced.", "contents": "A32390A, a new biologically active metabolite. I. Discovery and fermentation studies. A32390A is an isonitrile-containing derivative of diacyl D-mannitol. The compound is produced in fermentation as the major component of a metabolic complex known as A32390. A32390A inhibits dopamine-beta-hydroxylase reduces heart and adrenal norepinephrine levels, lowers blood pressure in hypertensive rats, and possesses antibiotic activity vs. Gram-positive bacteria and fungi, including Candida albicans. A32390 is produced in submerged culture by a mold, a species of Pyrenochaeta, NRRL-5786. Glucose and sucrose are among the best carbon sources for the biosynthesis of A32390. Mannitol, although a substituent of the A32390A molecule, supports little or no biosynthesis of the compound when employed as the major carbon source for the fermentation. The addition of crotonic acid derivatives. ethanol, or L-histidine to the fermentation medium enhances the level of A32390 produced."}
{"id": "PMID:24037", "title": "Regulation of gamma-aminobutyric acid degradation in Escherichia coli by nitrogen metabolism enzymes.", "content": "The possible role of glutamate dehydrogenase, glutamate synthase, and glutamine synthetase in the regulation of enzyme formation in the gamma-aminobutyric acid (GABA) catabolic pathway of Escherichia coli K-12 was investigated. Evidence is presented indicating that glutamine synthetase acts as a positive regulator in the E. coli GABA control system. Mutations impairing glutamate synthase activity prevent the depression of the enzymes of the GABA pathway in ammonia-limited glucose media. However, mutations resulting in constitutive synthesis of glutamine synthetase (GlnC) restore the ability of the glutamate synthase-less mutants to grow in glucose-GABA media and result in depressed synthesis of the GABA enzymes. It is suggested that the loss of glutamate synthesis activity affects the GABA control system indirectly by lowering glutamine synthetase levels.", "contents": "Regulation of gamma-aminobutyric acid degradation in Escherichia coli by nitrogen metabolism enzymes. The possible role of glutamate dehydrogenase, glutamate synthase, and glutamine synthetase in the regulation of enzyme formation in the gamma-aminobutyric acid (GABA) catabolic pathway of Escherichia coli K-12 was investigated. Evidence is presented indicating that glutamine synthetase acts as a positive regulator in the E. coli GABA control system. Mutations impairing glutamate synthase activity prevent the depression of the enzymes of the GABA pathway in ammonia-limited glucose media. However, mutations resulting in constitutive synthesis of glutamine synthetase (GlnC) restore the ability of the glutamate synthase-less mutants to grow in glucose-GABA media and result in depressed synthesis of the GABA enzymes. It is suggested that the loss of glutamate synthesis activity affects the GABA control system indirectly by lowering glutamine synthetase levels."}
{"id": "PMID:24038", "title": "Mitochondrial adenosine triphosphatase of wild-type and poky Neurospora crassa.", "content": "We have compared the adenosine triphosphatase (ATPase) activity of mitochondria prepared from wild-type Neurospora crassa and from poky, a maternally inherited mutant known to possess defective mitochondrial ribosomes and reduced amounts of cytochromes aa3 and b. poky contains two distinct forms of mitochondrial ATPase. The first is normal in its Km for ATP, specificity for nucleotides and divalent cations, pH optimum, cold stability, and sensitivity to inhibitors (oligomycin, N,N-dicyclohexyl carbodiimide, and adenylyl imidodiphosphate). The fact that membrane-bound, cold-stable, oligomycin-sensitive ATPase activity is present in poky (with an activity of 1.93 +/- 0.03 mumol/min-mg of protein compared with 1.33 +/- 0.07 mumol/min-mg of protein in the wild-type strain) and also in chloramphenicol-grown wild-type cells suggests that products of mitochondrial protein synthesis play only a limited role in the attachment of the mitochondrial ATPase to the membrane in Neurospora. poky also contains a second form of mitochondrial ATPase, which has an activity of 1.5 +/- 0.2 mumol/min-mg of protein, is oligomycin sensitive but cold labile, and presumably is attached less firmly to the mitochondrial membrane. The two forms, added together, represent a substantial overproduction of mitochondrial ATPase by poky.", "contents": "Mitochondrial adenosine triphosphatase of wild-type and poky Neurospora crassa. We have compared the adenosine triphosphatase (ATPase) activity of mitochondria prepared from wild-type Neurospora crassa and from poky, a maternally inherited mutant known to possess defective mitochondrial ribosomes and reduced amounts of cytochromes aa3 and b. poky contains two distinct forms of mitochondrial ATPase. The first is normal in its Km for ATP, specificity for nucleotides and divalent cations, pH optimum, cold stability, and sensitivity to inhibitors (oligomycin, N,N-dicyclohexyl carbodiimide, and adenylyl imidodiphosphate). The fact that membrane-bound, cold-stable, oligomycin-sensitive ATPase activity is present in poky (with an activity of 1.93 +/- 0.03 mumol/min-mg of protein compared with 1.33 +/- 0.07 mumol/min-mg of protein in the wild-type strain) and also in chloramphenicol-grown wild-type cells suggests that products of mitochondrial protein synthesis play only a limited role in the attachment of the mitochondrial ATPase to the membrane in Neurospora. poky also contains a second form of mitochondrial ATPase, which has an activity of 1.5 +/- 0.2 mumol/min-mg of protein, is oligomycin sensitive but cold labile, and presumably is attached less firmly to the mitochondrial membrane. The two forms, added together, represent a substantial overproduction of mitochondrial ATPase by poky."}
{"id": "PMID:24039", "title": "Catabolic N2-acetylornithine 5-aminotransferase of Klebsiella aerogenes: control of synthesis by induction, catabolite repression, and activation by glutamine synthetase.", "content": "Klebsiella aerogenes formed two N2-acetylornithine 5-aminotransferases (ACOAT) which were separable by diethylaminoethyl-cellulose chromatography. One ACOAT was repressed when the cells grew on arginine-containing medium, indicating its function in arginine biosynthesis. The second ACOAT was induced when arginine or ornithine was present in the medium as the sole source of carbon or nitrogen, suggesting its function in the catabolism of these compounds. The induced enzyme was purified almost to homogeneity. Its molecular weight is 59,000; it is a pyridoxal 5-phosphate-dependent enzyme and exhibits activity with N2-acetylornithine (Km = 1.1 mM) as well as with ornithine (Km = 5.4 mM). ACOAT did not catalyze the transamination of putrescine or 4-aminobutyrate. The best amino acceptor was 2-ketoglutarate (Km = 0.7 mM). ACOAT formation was subject to catabolite repression exerted by glucose when ammonia was present in excess. When the cells were deprived of nitrogen, ACOAT escaped from catabolite repression. This activation was mediated by glutamine synthetase as shown by the fact that mutants affected in the regulation or synthesis of glutamine synthetase were also affected in the control of ACOAT formation.", "contents": "Catabolic N2-acetylornithine 5-aminotransferase of Klebsiella aerogenes: control of synthesis by induction, catabolite repression, and activation by glutamine synthetase. Klebsiella aerogenes formed two N2-acetylornithine 5-aminotransferases (ACOAT) which were separable by diethylaminoethyl-cellulose chromatography. One ACOAT was repressed when the cells grew on arginine-containing medium, indicating its function in arginine biosynthesis. The second ACOAT was induced when arginine or ornithine was present in the medium as the sole source of carbon or nitrogen, suggesting its function in the catabolism of these compounds. The induced enzyme was purified almost to homogeneity. Its molecular weight is 59,000; it is a pyridoxal 5-phosphate-dependent enzyme and exhibits activity with N2-acetylornithine (Km = 1.1 mM) as well as with ornithine (Km = 5.4 mM). ACOAT did not catalyze the transamination of putrescine or 4-aminobutyrate. The best amino acceptor was 2-ketoglutarate (Km = 0.7 mM). ACOAT formation was subject to catabolite repression exerted by glucose when ammonia was present in excess. When the cells were deprived of nitrogen, ACOAT escaped from catabolite repression. This activation was mediated by glutamine synthetase as shown by the fact that mutants affected in the regulation or synthesis of glutamine synthetase were also affected in the control of ACOAT formation."}
{"id": "PMID:24040", "title": "Effect of glucose starvation on the nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase of yeast.", "content": "Yeast cells growing on mineral medium plus ammonia and glucose contained high levels of nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase activity, as measured in crude extracts. After suspension of cells in fresh medium lacking glucose, there was a loss of the glutamate dehydrogenase activity. Loss of activity was inhibited by 2,4-dinitrophenol, sodium azide, iodoacetic acid, and cycloheximide. The enzyme activity was restored when glucose was added back to the medium, and this recovery was fully prevented in the presence of cycloheximide.", "contents": "Effect of glucose starvation on the nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase of yeast. Yeast cells growing on mineral medium plus ammonia and glucose contained high levels of nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase activity, as measured in crude extracts. After suspension of cells in fresh medium lacking glucose, there was a loss of the glutamate dehydrogenase activity. Loss of activity was inhibited by 2,4-dinitrophenol, sodium azide, iodoacetic acid, and cycloheximide. The enzyme activity was restored when glucose was added back to the medium, and this recovery was fully prevented in the presence of cycloheximide."}
{"id": "PMID:24041", "title": "Evidence for the degradation of nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase of Candida utilis during rapid enzyme inactivation.", "content": "The nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase (NADP-GDH) from the food yeast Candida utilis was found to be rapidly inactivated when cultures were starved of a carbon source. The addition of glutamate or alanine to the starvation medium stimulated the rate of inactivation. Loss of enzyme activity was irreversible since the reappearance of enzyme activity, following the addition of glucose to carbon-starved cultures, was blocked by cycloheximide. A specific rabbit antibody was prepared against the NADP-GDH from C. utilis and used to quantitate the enzyme during inactivation promoted by carbon starvation. The amount of precipitable antigenic material paralleled the rapid decrease of enzyme activity observed after transition of cells from NH(4) (+)-glucose to glutamate medium. No additional small-molecular-weight protein was precipitated by the antibody as a result of the inactivation, suggesting that the enzyme is considerably altered during the primary steps of the inactivation process. Analysis by immunoprecipitation of the reappearance of enzyme activity after enzyme inactivation showed that increase of NADP-GDH activity was almost totally due to de novo synthesis, ruling out the possibility that enzyme activity modulation is achieved by reversible covalent modification. Enzyme degradation was also measured during steady-state growth and other changes in nitrogen and carbon status of the culture media. In all instances so far estimated, the enzyme was found to be very stable and not normally subject to high rates of degradation. Therefore, the possibility that inactivation was caused by a change in the ratio of synthesis to degradation can be excluded.", "contents": "Evidence for the degradation of nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase of Candida utilis during rapid enzyme inactivation. The nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase (NADP-GDH) from the food yeast Candida utilis was found to be rapidly inactivated when cultures were starved of a carbon source. The addition of glutamate or alanine to the starvation medium stimulated the rate of inactivation. Loss of enzyme activity was irreversible since the reappearance of enzyme activity, following the addition of glucose to carbon-starved cultures, was blocked by cycloheximide. A specific rabbit antibody was prepared against the NADP-GDH from C. utilis and used to quantitate the enzyme during inactivation promoted by carbon starvation. The amount of precipitable antigenic material paralleled the rapid decrease of enzyme activity observed after transition of cells from NH(4) (+)-glucose to glutamate medium. No additional small-molecular-weight protein was precipitated by the antibody as a result of the inactivation, suggesting that the enzyme is considerably altered during the primary steps of the inactivation process. Analysis by immunoprecipitation of the reappearance of enzyme activity after enzyme inactivation showed that increase of NADP-GDH activity was almost totally due to de novo synthesis, ruling out the possibility that enzyme activity modulation is achieved by reversible covalent modification. Enzyme degradation was also measured during steady-state growth and other changes in nitrogen and carbon status of the culture media. In all instances so far estimated, the enzyme was found to be very stable and not normally subject to high rates of degradation. Therefore, the possibility that inactivation was caused by a change in the ratio of synthesis to degradation can be excluded."}
{"id": "PMID:24042", "title": "Effect of external environmental factors on the morphology of Spiroplasma citri.", "content": "Spiroplasma citri was examined by electron microscopy for morphological changes when maintained under a variety of conditions. PPLO serum fraction maintained spiral and helical morphology of S. citri at pH values of 8.0, 7.5, and 7.0, but only partially at pH 6.0 and 5.0. The absence of PPLO serum fraction resulted in round, deteriorated cells at all pH values tested. Bovine serum albumin (BSA), Phytone, soluble starch, potato starch, spermine, lipid-extracted PPLO serum fraction, and lipid-extracted BSA could substitute for PPLO serum fraction in maintaining spiral and helical morphology at pH 7.5. At pH 5.0, only BSA, lipid-extracted BSA, and lipid-extracted PPLO serum fraction were effective. Only BSA supported growth of S. citri for more than two transfers, whereas all other substitutes could not support growth longer than two transfers.", "contents": "Effect of external environmental factors on the morphology of Spiroplasma citri. Spiroplasma citri was examined by electron microscopy for morphological changes when maintained under a variety of conditions. PPLO serum fraction maintained spiral and helical morphology of S. citri at pH values of 8.0, 7.5, and 7.0, but only partially at pH 6.0 and 5.0. The absence of PPLO serum fraction resulted in round, deteriorated cells at all pH values tested. Bovine serum albumin (BSA), Phytone, soluble starch, potato starch, spermine, lipid-extracted PPLO serum fraction, and lipid-extracted BSA could substitute for PPLO serum fraction in maintaining spiral and helical morphology at pH 7.5. At pH 5.0, only BSA, lipid-extracted BSA, and lipid-extracted PPLO serum fraction were effective. Only BSA supported growth of S. citri for more than two transfers, whereas all other substitutes could not support growth longer than two transfers."}
{"id": "PMID:24043", "title": "The ATPase reaction in the steady state and in the initial burst catalyzed by chicken gizzard myosin in 0.6 M KCl1.", "content": "On studying the steady-state activity in 0.6 M KCl, it was found that Mg-ATPase of chicken gizzard myosin was identical with that of rabbit skeletal myosin in the pH-activity profile, Michaelis-Menten constant, and maximum velocity. As regards the \"initial burst\" of ATP splitting in the presence of Mg (0.6 M KCl), it was found that gizzard and skeletal myosins were identical both in the size of the initial burst and in the velocity-ATP concentration relationship. The only difference we observed was that the Ca- and EDTA-ATPase activities of gizzard myosin were, as reported by other investigators, approximately one-half to one-third of those of skeletal myosin, although the pH-activity profiles for the ATPase of gizzard myosin was essentially the same as that of skeletal myosin.", "contents": "The ATPase reaction in the steady state and in the initial burst catalyzed by chicken gizzard myosin in 0.6 M KCl1. On studying the steady-state activity in 0.6 M KCl, it was found that Mg-ATPase of chicken gizzard myosin was identical with that of rabbit skeletal myosin in the pH-activity profile, Michaelis-Menten constant, and maximum velocity. As regards the \"initial burst\" of ATP splitting in the presence of Mg (0.6 M KCl), it was found that gizzard and skeletal myosins were identical both in the size of the initial burst and in the velocity-ATP concentration relationship. The only difference we observed was that the Ca- and EDTA-ATPase activities of gizzard myosin were, as reported by other investigators, approximately one-half to one-third of those of skeletal myosin, although the pH-activity profiles for the ATPase of gizzard myosin was essentially the same as that of skeletal myosin."}
{"id": "PMID:24045", "title": "Modification of rabbit muscle phosphorylase b by a water-soluble carbodiimide.", "content": "Glycogen phosphorylase b from rabbit muscle was rapidly inactivated by incubation with 1-cyclohexyl-3-(2-morpholinyl-(4)-ethyl)carbodiimide metho-p-toluenesulfonate (CMC) at pH 5.1. The inactivation was pH-dependent and was not restored by treatment with hydroxylamine. The addition of glycine ethyl ester or N-(2,4-dinitrophenyl)-ethylenediamine (DNP-EDA) markedly increased the rate of inactivation. Of the various amino analogs of glucose tested, only glucosyl amine accelerated the inactivation, although they are all bound to the glucose 1-phosphate site of the enzyme. In the absence of amines, incorporation of about 3 mol of [metho-14C]CMC per protein monomer was observed on complete inactivation. In the presence of DNP-EDA, however, only 2 mol of [metho-14C]CMC and 1 mol of DNP-EDA were incorporated before the activity was completely lost. The treatment of phosphorylase b with CMC did not change the Km values of the enzyme for glucose 1-phosphate and AMP, in spite of the 56% inactivation. It is suggested that, in the phosphorylase-catalyzed reaction, an essential carboxyl group of the enzyme plays a role in the protonation of the glucosidic oxygen of glucose 1-phosphate.", "contents": "Modification of rabbit muscle phosphorylase b by a water-soluble carbodiimide. Glycogen phosphorylase b from rabbit muscle was rapidly inactivated by incubation with 1-cyclohexyl-3-(2-morpholinyl-(4)-ethyl)carbodiimide metho-p-toluenesulfonate (CMC) at pH 5.1. The inactivation was pH-dependent and was not restored by treatment with hydroxylamine. The addition of glycine ethyl ester or N-(2,4-dinitrophenyl)-ethylenediamine (DNP-EDA) markedly increased the rate of inactivation. Of the various amino analogs of glucose tested, only glucosyl amine accelerated the inactivation, although they are all bound to the glucose 1-phosphate site of the enzyme. In the absence of amines, incorporation of about 3 mol of [metho-14C]CMC per protein monomer was observed on complete inactivation. In the presence of DNP-EDA, however, only 2 mol of [metho-14C]CMC and 1 mol of DNP-EDA were incorporated before the activity was completely lost. The treatment of phosphorylase b with CMC did not change the Km values of the enzyme for glucose 1-phosphate and AMP, in spite of the 56% inactivation. It is suggested that, in the phosphorylase-catalyzed reaction, an essential carboxyl group of the enzyme plays a role in the protonation of the glucosidic oxygen of glucose 1-phosphate."}
{"id": "PMID:24047", "title": "Kinetic studies on redox reactions of hemoproteins. II. Reduction of thermoresistant cytochrome c-552 and horse heart cytochrome c by ascorbic acid.", "content": "The reductions of thermoresistant cytochrome c-552 and horse heart cytochrome c by ascorbic acid were studied by the stopped-flow method between pH 4 and 10. The results were as follows (1) The reduction of horse heart cytochrome c showed two relaxation decays above pH 8.5, one of which was pseudo-first order, as was the case below pH 8, while the other was nearly concentration-independent. These results were consistent with those reported by Greenwood and Palmer (J. Biol. Chem. (1965) 240, 3660-3663). (2) For the reduction of cytochrome c-552, only a single relaxational decay that obeyed pseudo-first order kinetics was observed. (3) It seems most reasonable to assume that the concentration-independent relaxation process can be attributed to the isomerization reaction accompanying ligand exchange, since it is known that only horse heart cytochrome c exhibits ligand exchange, involving a residue with pK 9.3.", "contents": "Kinetic studies on redox reactions of hemoproteins. II. Reduction of thermoresistant cytochrome c-552 and horse heart cytochrome c by ascorbic acid. The reductions of thermoresistant cytochrome c-552 and horse heart cytochrome c by ascorbic acid were studied by the stopped-flow method between pH 4 and 10. The results were as follows (1) The reduction of horse heart cytochrome c showed two relaxation decays above pH 8.5, one of which was pseudo-first order, as was the case below pH 8, while the other was nearly concentration-independent. These results were consistent with those reported by Greenwood and Palmer (J. Biol. Chem. (1965) 240, 3660-3663). (2) For the reduction of cytochrome c-552, only a single relaxational decay that obeyed pseudo-first order kinetics was observed. (3) It seems most reasonable to assume that the concentration-independent relaxation process can be attributed to the isomerization reaction accompanying ligand exchange, since it is known that only horse heart cytochrome c exhibits ligand exchange, involving a residue with pK 9.3."}
{"id": "PMID:24049", "title": "Genetic expression of microsomal electron transport in mice. Different patterns of dependence of constitutive cytochrome P-450 reductase activity of pyridine nucleotide concentrations.", "content": "Cytochrome P-450 reductase and aryl hydrocarbon hydroxylase activities were investigated in hepatic microsomes from untreated C57BL/6J, DBA/2J, B6D2F1, and (B6D2) D2 mice. The dependence of the rate of P-450 reduction on the concentration of added pyridine nucleotide (NADPH or NADH) was biphasic in DBA/2J microsomes but monophasic in C57BL/6J microsomes. Analogous strain-specific patterns were observed when the dependence of the rate of benzpyrene hydroxylation on NADPH concentration was examined. In crosses between the two inbred strains and between B6D2F1 mice and DBA/2J mice, the biphasic pattern for both the reductase and the hydroxylase activities was found to co-segregate with the recessive allele for aromatic hydrocarbon responsiveness. These results might reflect an architectural difference between the microsomal electron transport systems of responsive and nonresponsive mice.", "contents": "Genetic expression of microsomal electron transport in mice. Different patterns of dependence of constitutive cytochrome P-450 reductase activity of pyridine nucleotide concentrations. Cytochrome P-450 reductase and aryl hydrocarbon hydroxylase activities were investigated in hepatic microsomes from untreated C57BL/6J, DBA/2J, B6D2F1, and (B6D2) D2 mice. The dependence of the rate of P-450 reduction on the concentration of added pyridine nucleotide (NADPH or NADH) was biphasic in DBA/2J microsomes but monophasic in C57BL/6J microsomes. Analogous strain-specific patterns were observed when the dependence of the rate of benzpyrene hydroxylation on NADPH concentration was examined. In crosses between the two inbred strains and between B6D2F1 mice and DBA/2J mice, the biphasic pattern for both the reductase and the hydroxylase activities was found to co-segregate with the recessive allele for aromatic hydrocarbon responsiveness. These results might reflect an architectural difference between the microsomal electron transport systems of responsive and nonresponsive mice."}
{"id": "PMID:24050", "title": "Oxygen equilibria of hybrid-heme hemoglobins containing proto- and mesoheme groups. On the nonequivalence of alpha and beta chains.", "content": "Hybrid-heme hemoglobins, alpha(meso)2beta(proto)2 and alpha(proto)2beta(meso)2, were prepared, and the O2 equilibria of their alpha and beta chains were measured separately at the isosbestic points of the partner chains at different pH values and in the presence and absence of inositol hexaphosphate. The Adair equation was extended to distinguish between the O2 saturations of the alpha and beta chains, and the seven equilibrium parameters were obtained by curve fitting to those equations. The results showed that the beta chains have an affinity slightly higher than the alpha chains in the binding of the first O2 molecule. For the second O2 molecule, the molecular species that has been oxygenated on the alpha chain has a higher affinity than that carrying O2 on the beta chain. The slopes of the Hill plots were higher for the alpha chain. The O2 saturation curves for the alpha and beta chains were calculated from the parameters averaged for the hybrids alpha(meso)2beta(proto)2 and alpha(proto)2beta(meso)2 in order to cancel the effects of the heme replacement. The curves showed that the difference in O2 saturation between the two kinds of chains depends on the conditions and on the degree of O2 saturation. It was concluded that the functional difference between the chains is small enough so that it is not required to modify the models already accepted for the cooperativity of hemoglobin.", "contents": "Oxygen equilibria of hybrid-heme hemoglobins containing proto- and mesoheme groups. On the nonequivalence of alpha and beta chains. Hybrid-heme hemoglobins, alpha(meso)2beta(proto)2 and alpha(proto)2beta(meso)2, were prepared, and the O2 equilibria of their alpha and beta chains were measured separately at the isosbestic points of the partner chains at different pH values and in the presence and absence of inositol hexaphosphate. The Adair equation was extended to distinguish between the O2 saturations of the alpha and beta chains, and the seven equilibrium parameters were obtained by curve fitting to those equations. The results showed that the beta chains have an affinity slightly higher than the alpha chains in the binding of the first O2 molecule. For the second O2 molecule, the molecular species that has been oxygenated on the alpha chain has a higher affinity than that carrying O2 on the beta chain. The slopes of the Hill plots were higher for the alpha chain. The O2 saturation curves for the alpha and beta chains were calculated from the parameters averaged for the hybrids alpha(meso)2beta(proto)2 and alpha(proto)2beta(meso)2 in order to cancel the effects of the heme replacement. The curves showed that the difference in O2 saturation between the two kinds of chains depends on the conditions and on the degree of O2 saturation. It was concluded that the functional difference between the chains is small enough so that it is not required to modify the models already accepted for the cooperativity of hemoglobin."}
{"id": "PMID:24052", "title": "Dibutyryl cyclic AMP increases the amount of functional messenger RNA coding for tyrosine aminotransferase in rat liver.", "content": "The administration of N6,O2-dibutyryl cyclic AMP and theophylline to adrenalectomized rats results in an increase in the amount of functional mRNA coding for tyrosine aminotransferase that can be isolated from liver. The induction of this specific mRNA, as quantitated in a mRNA-dependent reticulocyte lysate system, and using poly(A)+ mRNA extracted from total tissue and polysomes, is very rapid. Within an hour after the intraperitoneal injection of the cyclic AMP derivative there is a 5- to 7-fold elevation of functional mRNA coding for tyrosine aminotransferase (mRNATAT), and by 3 h this has returned to basal levels. In contrast, the 4- to 5-fold induction of tyrosine aminotransferase catalytic activity is maximal at 2 h and is still significantly greater than the basal level at 5 h. In the basal state, tyrosine aminotransferase mRNA codes for 0.019 +/- 0.003% of the protein synthesized in the in vitro system, whereas after cyclic nucleotide treatment this value 0.115 +/- 0.015%, hence the increase in mRNATAT activity is relatively specific. Cordycepin, at a concentration which prevents the accumulation in cytoplasm of poly(A)+ mRNA, completely blocks the increase in both the catalytic and mRNA activity of this enzyme. The marked increase in functional mRNA, the requirement for continued synthesis of poly(A)+ RNA, and the rapid induction and deinduction suggest that the cyclic nucleotide is enhancing specific mRNA synthesis and/or, processing, however an effect on mRNA degradation cannot be excluded.", "contents": "Dibutyryl cyclic AMP increases the amount of functional messenger RNA coding for tyrosine aminotransferase in rat liver. The administration of N6,O2-dibutyryl cyclic AMP and theophylline to adrenalectomized rats results in an increase in the amount of functional mRNA coding for tyrosine aminotransferase that can be isolated from liver. The induction of this specific mRNA, as quantitated in a mRNA-dependent reticulocyte lysate system, and using poly(A)+ mRNA extracted from total tissue and polysomes, is very rapid. Within an hour after the intraperitoneal injection of the cyclic AMP derivative there is a 5- to 7-fold elevation of functional mRNA coding for tyrosine aminotransferase (mRNATAT), and by 3 h this has returned to basal levels. In contrast, the 4- to 5-fold induction of tyrosine aminotransferase catalytic activity is maximal at 2 h and is still significantly greater than the basal level at 5 h. In the basal state, tyrosine aminotransferase mRNA codes for 0.019 +/- 0.003% of the protein synthesized in the in vitro system, whereas after cyclic nucleotide treatment this value 0.115 +/- 0.015%, hence the increase in mRNATAT activity is relatively specific. Cordycepin, at a concentration which prevents the accumulation in cytoplasm of poly(A)+ mRNA, completely blocks the increase in both the catalytic and mRNA activity of this enzyme. The marked increase in functional mRNA, the requirement for continued synthesis of poly(A)+ RNA, and the rapid induction and deinduction suggest that the cyclic nucleotide is enhancing specific mRNA synthesis and/or, processing, however an effect on mRNA degradation cannot be excluded."}
{"id": "PMID:24055", "title": "Purification and subunit structure of rat mammary gland acetyl coenzyme A carboxylase.", "content": "1. Acetyl coenzyme A carboxylase from lactating rat mammary gland has been purified to apparent homogeneity. 2. The purified enzyme has the following characteristics: (a) its specific activity approaches 15 units/mg of protein, (b) the sedimentation constants of the protomeric and polymeric forms of the enzyme are 12 to 13 S and greater than or equal to 40 S, respectively, (c) the polymeric form of the enzyme shows filamentous structures in the electron microscope, and (d) the polypeptide(s) arising from its dissociation reveals a single major component of Mr = 240,000 to 260,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 3. The enzyme contains 1 mol of biotin and approximately 6 mol of phosphate/240,000 g of protein.", "contents": "Purification and subunit structure of rat mammary gland acetyl coenzyme A carboxylase. 1. Acetyl coenzyme A carboxylase from lactating rat mammary gland has been purified to apparent homogeneity. 2. The purified enzyme has the following characteristics: (a) its specific activity approaches 15 units/mg of protein, (b) the sedimentation constants of the protomeric and polymeric forms of the enzyme are 12 to 13 S and greater than or equal to 40 S, respectively, (c) the polymeric form of the enzyme shows filamentous structures in the electron microscope, and (d) the polypeptide(s) arising from its dissociation reveals a single major component of Mr = 240,000 to 260,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 3. The enzyme contains 1 mol of biotin and approximately 6 mol of phosphate/240,000 g of protein."}
{"id": "PMID:24057", "title": "Prune-bell syndrome: a report of twelve cases and review of the literature.", "content": "Prune-belly syndrome is a rare congenital disease involving a deficiency of abdominal muscles, genitourinary abnormalities, and cryptorchidism. About half of the patients with the disease have associated musculoskeletal abnormalities, including club foot and dislocation of the hip. We saw twelve patients with this disease, four of whom required extensive orthopaedic treatment.", "contents": "Prune-bell syndrome: a report of twelve cases and review of the literature. Prune-belly syndrome is a rare congenital disease involving a deficiency of abdominal muscles, genitourinary abnormalities, and cryptorchidism. About half of the patients with the disease have associated musculoskeletal abnormalities, including club foot and dislocation of the hip. We saw twelve patients with this disease, four of whom required extensive orthopaedic treatment."}
{"id": "PMID:24058", "title": "Survival of Streptococcus pneumoniae in sputum from patients with pneumonia.", "content": "The isolation rate of Streptococcus pneumoniae in sputum cultures from patients with pneumococcal pneumonia is low. An investigation was made to determine whether this low yield might be due to loss of pneumocci and/or overgrowth by pharyngeal flora before the specimen is plated. Pneumococcal survival times and pharyngeal overgrowth at 4 degrees C and at room temperature were determined in sputum obtained from 42 patients with pneumococcal pneumonia. It was found that pneumococci survived for long periods in sputum--2.2 +/- 1.4 days at room temperature and 9.5 +/- 3.6 days at 4 degrees C. Overgrowth by pharyngeal flora occurred in only 6 of 42 specimens kept at 4 degrees C and 31 of 42 specimens kept at room temperature. The low yield of S. pneumoniae in sputum from patients with pneumococcal pneumonia is not explained by decreased viability of the organism.", "contents": "Survival of Streptococcus pneumoniae in sputum from patients with pneumonia. The isolation rate of Streptococcus pneumoniae in sputum cultures from patients with pneumococcal pneumonia is low. An investigation was made to determine whether this low yield might be due to loss of pneumocci and/or overgrowth by pharyngeal flora before the specimen is plated. Pneumococcal survival times and pharyngeal overgrowth at 4 degrees C and at room temperature were determined in sputum obtained from 42 patients with pneumococcal pneumonia. It was found that pneumococci survived for long periods in sputum--2.2 +/- 1.4 days at room temperature and 9.5 +/- 3.6 days at 4 degrees C. Overgrowth by pharyngeal flora occurred in only 6 of 42 specimens kept at 4 degrees C and 31 of 42 specimens kept at room temperature. The low yield of S. pneumoniae in sputum from patients with pneumococcal pneumonia is not explained by decreased viability of the organism."}
{"id": "PMID:24059", "title": "Quantitative evaluation of three commercial blood culture media for growth of anaerobic organisms.", "content": "The ability of three different commercial blood culture media--brain heart infusion broth (Pfizer), thiol broth (Difco), and PRS-peptone broth (Becton, Dickinson & Co.)--to support the growth of five different anaerobes is described. Inocula of 100 and 1,000 colony-forming units per ml were used to evaluate potential differences in survival, lag time, growth rate, and doubling times of each anaerobe in each medium. In addition, each medium was evaluated for its ability to neutralize the antibacterial effects of whole blood. The results of this study indicate that the PRS-peptone broth is superior to brain heart infusion and thiol broths. Shorter lag times and accelerated generation times and growth rates were noted for more different anaerobes in the PRS-peptone broth. Neither the size of inoculum nor the addition of normal whole blood appeared to alter the survival or growth characteristics of the anaerobes in any medium. However, the addition of normal whole blood did extend the lag time of each anaerobe by approximately 1 to 2 h in each medium.", "contents": "Quantitative evaluation of three commercial blood culture media for growth of anaerobic organisms. The ability of three different commercial blood culture media--brain heart infusion broth (Pfizer), thiol broth (Difco), and PRS-peptone broth (Becton, Dickinson & Co.)--to support the growth of five different anaerobes is described. Inocula of 100 and 1,000 colony-forming units per ml were used to evaluate potential differences in survival, lag time, growth rate, and doubling times of each anaerobe in each medium. In addition, each medium was evaluated for its ability to neutralize the antibacterial effects of whole blood. The results of this study indicate that the PRS-peptone broth is superior to brain heart infusion and thiol broths. Shorter lag times and accelerated generation times and growth rates were noted for more different anaerobes in the PRS-peptone broth. Neither the size of inoculum nor the addition of normal whole blood appeared to alter the survival or growth characteristics of the anaerobes in any medium. However, the addition of normal whole blood did extend the lag time of each anaerobe by approximately 1 to 2 h in each medium."}
{"id": "PMID:24061", "title": "A double-blind controlled study of pipothiazine palmitate in the maintenance treatment of schizophrenic outpatients.", "content": "In a double-blind controlled study lasting 9 months, pipothiazine palmitate, a long-acting neuroleptic that can be administered intramuscularly once a month, was compared with fluphenazine enanthate in the maintenance treatment of 32 schizophrenic outpatients. Before the trial commenced, all patients were being treated with fluphenazine enanthate. The results indicate that pipothiazine palmitate was not as potent a neuroleptic as fluphenazine enanthate. Pipothiazine appears to resemble fluphenazine enanthate in its capacity to induce parkinsonism and tardive dyskinesia.", "contents": "A double-blind controlled study of pipothiazine palmitate in the maintenance treatment of schizophrenic outpatients. In a double-blind controlled study lasting 9 months, pipothiazine palmitate, a long-acting neuroleptic that can be administered intramuscularly once a month, was compared with fluphenazine enanthate in the maintenance treatment of 32 schizophrenic outpatients. Before the trial commenced, all patients were being treated with fluphenazine enanthate. The results indicate that pipothiazine palmitate was not as potent a neuroleptic as fluphenazine enanthate. Pipothiazine appears to resemble fluphenazine enanthate in its capacity to induce parkinsonism and tardive dyskinesia."}
{"id": "PMID:24060", "title": "Effects of antianxiety drug and personality on stress-inducing psychomotor performance test.", "content": "The present study was carried out to clarify the effects of an antianxiety drug and of personality characteristics on a psychomotor performance test. Forty-eight healthy women college students were chosen from 64 volunteers as having either high or low levels of trait anxiety, neuroticism, or extroversion. Subjects with high trait anxiety and/or neuroticism tended to show a decrease in both speed and accuracy of the mirror drawing test (MDT) in the initial nondrug trials. Bromazepam, 5 mg, a benzodiazepine derivative, decreased this decrement in highly anxious subjects but worsened the speed in less anxious subjects. The personality traits of subjects, as well as the degree to which a performance test will induce stress, must be considered when evaluating the effects of antianxiety drugs on the performance of normal volunteers. The clinical anxiety-reducing efficacy of drugs may be predicted by using the MDT in subjects with high levels of anxiety and/or neuroticism.", "contents": "Effects of antianxiety drug and personality on stress-inducing psychomotor performance test. The present study was carried out to clarify the effects of an antianxiety drug and of personality characteristics on a psychomotor performance test. Forty-eight healthy women college students were chosen from 64 volunteers as having either high or low levels of trait anxiety, neuroticism, or extroversion. Subjects with high trait anxiety and/or neuroticism tended to show a decrease in both speed and accuracy of the mirror drawing test (MDT) in the initial nondrug trials. Bromazepam, 5 mg, a benzodiazepine derivative, decreased this decrement in highly anxious subjects but worsened the speed in less anxious subjects. The personality traits of subjects, as well as the degree to which a performance test will induce stress, must be considered when evaluating the effects of antianxiety drugs on the performance of normal volunteers. The clinical anxiety-reducing efficacy of drugs may be predicted by using the MDT in subjects with high levels of anxiety and/or neuroticism."}
{"id": "PMID:24067", "title": "The effect of Skylab on the chemical composition of saliva.", "content": "The levels of specific proteins and electrolytes in stimulated whole saliva were monitored in Skylab crew members before and after each mission. With few exceptions, mission-associated compositional changes in saliva were relatively minimal. There were no changes in(formula see text), Cl-, albumin, or IgG concentrations. There were slight decreases in total protein coinciding with moderate saliva flow rate increases immediately before and after each flight. Other changes included diminutions in Na+ and lysozyme, and elevations in Mg++ and IgA. The IgA increase was the most pronounced mission-associated change observed.", "contents": "The effect of Skylab on the chemical composition of saliva. The levels of specific proteins and electrolytes in stimulated whole saliva were monitored in Skylab crew members before and after each mission. With few exceptions, mission-associated compositional changes in saliva were relatively minimal. There were no changes in(formula see text), Cl-, albumin, or IgG concentrations. There were slight decreases in total protein coinciding with moderate saliva flow rate increases immediately before and after each flight. Other changes included diminutions in Na+ and lysozyme, and elevations in Mg++ and IgA. The IgA increase was the most pronounced mission-associated change observed."}
{"id": "PMID:24068", "title": "Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction product with superior sensitivity for visualizing neural afferents and efferents.", "content": "Tetramethyl benzidine (TMB) is a presumptively non-carcinogenic chromogen which yields a blue reaction-product at sites of horseradish peroxidase activity. Sixty-six distinct procedures were performed in rats and monkeys in order to determine the optimal incubation parameters for TMB. As a result, a procedure is recommended whose sensitivity greatly surpasses that of a previously described benzidine dihydrochloride method. Indeed, the sensitivity of this new method in demonstrating retrograde transport is markedly superior to that of the previously described benzidine dihydrochloride method. Furthermore, as a consequence of this enhanced sensitivity, many efferent connections of the injection site are also visualized. The injection site demonstrated by this TMB procedure is significantly larger than the one demonstrated when benzidine dihydrochloride or diaminobenzidine is used as a chromogen. Finally, this TMB procedure has been compared to two other TMB procedures and found to provide superior morphology and sensitivity.", "contents": "Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction product with superior sensitivity for visualizing neural afferents and efferents. Tetramethyl benzidine (TMB) is a presumptively non-carcinogenic chromogen which yields a blue reaction-product at sites of horseradish peroxidase activity. Sixty-six distinct procedures were performed in rats and monkeys in order to determine the optimal incubation parameters for TMB. As a result, a procedure is recommended whose sensitivity greatly surpasses that of a previously described benzidine dihydrochloride method. Indeed, the sensitivity of this new method in demonstrating retrograde transport is markedly superior to that of the previously described benzidine dihydrochloride method. Furthermore, as a consequence of this enhanced sensitivity, many efferent connections of the injection site are also visualized. The injection site demonstrated by this TMB procedure is significantly larger than the one demonstrated when benzidine dihydrochloride or diaminobenzidine is used as a chromogen. Finally, this TMB procedure has been compared to two other TMB procedures and found to provide superior morphology and sensitivity."}
{"id": "PMID:24069", "title": "The pH of the hamster sperm acrosome.", "content": "The pH of the hamster sperm acrosome was estimated by a method based on the distribution of monoamines between membrane enclosed volumes maintaining pH gradients. A fluorescent amine, 9-aminoacridine, was used to permit both microscopic and fluorometric measurements of amine distribution. Cauda epididymal hamster sperm incubated with 9-aminoacridine accumulated the amine in the acrosomal volume. In the presence of NH4Cl or the ionophore Nigericin (compounds which discharge pH gradients) 9-aminoacridine fluorescence disappeared from the acrosome. Amine distribution between the acrosome and external volume was estimated by fluorometric measurement of sperm filtrates in the presence and absence of NH4Cl and Nigericin. These values, together with an estimated acrosomal volume of 0.4mu3 were used to calculate an acrosomal pH of less than 5. In addition, an acrosomal pH of 5 or less was obtained with 14C-methylamine. We suggest that such an acidic acrosomal pH of 5 or less could serve to inhibit the activation or autoactivation of the acrosomal zymogen proacrosin to acrosin, a trypsin-like enzyme involved in fertilization.", "contents": "The pH of the hamster sperm acrosome. The pH of the hamster sperm acrosome was estimated by a method based on the distribution of monoamines between membrane enclosed volumes maintaining pH gradients. A fluorescent amine, 9-aminoacridine, was used to permit both microscopic and fluorometric measurements of amine distribution. Cauda epididymal hamster sperm incubated with 9-aminoacridine accumulated the amine in the acrosomal volume. In the presence of NH4Cl or the ionophore Nigericin (compounds which discharge pH gradients) 9-aminoacridine fluorescence disappeared from the acrosome. Amine distribution between the acrosome and external volume was estimated by fluorometric measurement of sperm filtrates in the presence and absence of NH4Cl and Nigericin. These values, together with an estimated acrosomal volume of 0.4mu3 were used to calculate an acrosomal pH of less than 5. In addition, an acrosomal pH of 5 or less was obtained with 14C-methylamine. We suggest that such an acidic acrosomal pH of 5 or less could serve to inhibit the activation or autoactivation of the acrosomal zymogen proacrosin to acrosin, a trypsin-like enzyme involved in fertilization."}
{"id": "PMID:24077", "title": "Effects of calcium on the absorption and retention of lead.", "content": "An inverse relationship between lead retention and dietary calcium content has been known to exist for many years, but the reasons for this association remained unknown. In rats, the manipulation of dietary calcium had no significant effect upon the absorption of lead, but calcium-deprived animals had decreased excretion and thus increased body retention of lead. Intraluminal calcium decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, lead bound to two heat-stable intestinal mucosal fractions which have been shown to bind calcium. Although more lead bound to the higher molecular weight fraction and more calcium bound to the lower molecular weight vitamin D-induced CaBP, substantial amounts of lead and calcium were found in both fractions. Further, the addition of calcium to test doses of lead markedly diminished the amount of lead bound by both fractions. Shared binding sites on absorptive proteins would explain why dietary calcium decreases lead absorption.", "contents": "Effects of calcium on the absorption and retention of lead. An inverse relationship between lead retention and dietary calcium content has been known to exist for many years, but the reasons for this association remained unknown. In rats, the manipulation of dietary calcium had no significant effect upon the absorption of lead, but calcium-deprived animals had decreased excretion and thus increased body retention of lead. Intraluminal calcium decreased the absorption of test doses of lead from the small intestine in a dose-related manner. We postulated that this occurred because the two metals competed for similar binding sites on intestinal mucosal proteins which were important in the absorptive process. In vivo, lead bound to two heat-stable intestinal mucosal fractions which have been shown to bind calcium. Although more lead bound to the higher molecular weight fraction and more calcium bound to the lower molecular weight vitamin D-induced CaBP, substantial amounts of lead and calcium were found in both fractions. Further, the addition of calcium to test doses of lead markedly diminished the amount of lead bound by both fractions. Shared binding sites on absorptive proteins would explain why dietary calcium decreases lead absorption."}
{"id": "PMID:24080", "title": "[Enzyme-immunological tests: determination of the activity of peroxidase with the aid of the \"Trinder reagent\" (author's transl)].", "content": "Most of the currently used enzyme-immunological tests employ horse radish peroxidase as a marker enzyme. A new method is described for the determination of extremely small quantities of peroxidase. This largely prevents the inactivation of the peroxidase by H2O2 and thereby permits a much longer incubation time. In the presence of 25 mmol/l phenol, 2 mmol/l 4-amino-antipyrin and 0.8 mmol/l H2O2, peroxidase catalyses the formation of a red quinonimine, whose increase in adsorption is directly proportional to the enzyme concentration.", "contents": "[Enzyme-immunological tests: determination of the activity of peroxidase with the aid of the \"Trinder reagent\" (author's transl)]. Most of the currently used enzyme-immunological tests employ horse radish peroxidase as a marker enzyme. A new method is described for the determination of extremely small quantities of peroxidase. This largely prevents the inactivation of the peroxidase by H2O2 and thereby permits a much longer incubation time. In the presence of 25 mmol/l phenol, 2 mmol/l 4-amino-antipyrin and 0.8 mmol/l H2O2, peroxidase catalyses the formation of a red quinonimine, whose increase in adsorption is directly proportional to the enzyme concentration."}
{"id": "PMID:24081", "title": "Thin layer chromatographic screening for methaqualone, phenothiazines, opiates and benzodiazepines.", "content": "A method is described which permits the simultaneous detection of methaqualone, phenothiazines, opiates and benzodiazepines in urine. Its diagnostic application is discussed. After cleavage of conjugates with hydrochloric acid, the substances are extracted and identified by thin-layer chromatography. In most cases analysis can be carried out using 2 solvent systems, phenothiazines, methaqualone and opiates being visualised using a three stage spray sequence. Since phenothiazines can interfere with the detection of methaqualone, a specific eluant is used to ensure reliable detection of the latter. Methaqualone can be positively identified by its characteristic metabolite pattern, whereas phenothiazines can only be detected as a group.", "contents": "Thin layer chromatographic screening for methaqualone, phenothiazines, opiates and benzodiazepines. A method is described which permits the simultaneous detection of methaqualone, phenothiazines, opiates and benzodiazepines in urine. Its diagnostic application is discussed. After cleavage of conjugates with hydrochloric acid, the substances are extracted and identified by thin-layer chromatography. In most cases analysis can be carried out using 2 solvent systems, phenothiazines, methaqualone and opiates being visualised using a three stage spray sequence. Since phenothiazines can interfere with the detection of methaqualone, a specific eluant is used to ensure reliable detection of the latter. Methaqualone can be positively identified by its characteristic metabolite pattern, whereas phenothiazines can only be detected as a group."}
{"id": "PMID:24082", "title": "Glutamate dehydrogenase from coelenterates is NADP specific.", "content": "Glutamate dehydrogenases detected in tissue extracts of a broad sample of coelenterate species all require NADP(H) as a co-substrate, rather than being capable of using either NAD(H) or NADP(H). In this respect, the coelenterate phyla appear to be unique in the animal kingdom.", "contents": "Glutamate dehydrogenase from coelenterates is NADP specific. Glutamate dehydrogenases detected in tissue extracts of a broad sample of coelenterate species all require NADP(H) as a co-substrate, rather than being capable of using either NAD(H) or NADP(H). In this respect, the coelenterate phyla appear to be unique in the animal kingdom."}
{"id": "PMID:24083", "title": "Purification and properties of beta-hydroxybutyrate dehydrogenase from Mycobacterium phlei ATCC354.", "content": "beta-Hydroxybutyrate dehydrogenase (EC 1.1.1.30) was purified 145-fold from Mycobacterium phlei ATCC354 by ammonium sulphate fractionation and DEAE-cellulose chromatography. The pH optima for oxidation and reduction reactions were 8.4 and 6.8 respectively. The purified enzyme was specific for NAD, NADH, acetoacetate and D(-)-beta-hydroxybutyrate. Km values for DL-beta-hydroxybutyrate and NAD were 7.4 mM and 0.66 mM respectively. The enzyme was inactivated by mercurial thiol inhibitors and by heat, but could be protected by NADH, Ca2+ and partially by Mn2+. The enzyme did not require metal ions and was insensitive to EDTA, glutathione, dithiothreitol, beta-mercaptoethanol and cysteine.", "contents": "Purification and properties of beta-hydroxybutyrate dehydrogenase from Mycobacterium phlei ATCC354. beta-Hydroxybutyrate dehydrogenase (EC 1.1.1.30) was purified 145-fold from Mycobacterium phlei ATCC354 by ammonium sulphate fractionation and DEAE-cellulose chromatography. The pH optima for oxidation and reduction reactions were 8.4 and 6.8 respectively. The purified enzyme was specific for NAD, NADH, acetoacetate and D(-)-beta-hydroxybutyrate. Km values for DL-beta-hydroxybutyrate and NAD were 7.4 mM and 0.66 mM respectively. The enzyme was inactivated by mercurial thiol inhibitors and by heat, but could be protected by NADH, Ca2+ and partially by Mn2+. The enzyme did not require metal ions and was insensitive to EDTA, glutathione, dithiothreitol, beta-mercaptoethanol and cysteine."}
{"id": "PMID:24084", "title": "Virulence and resistance to superoxide, low pH and hydrogen peroxide among strains of Mycobacterium tuberculosis.", "content": "Six strains of Mycobacterium tuberculosis of different virulence in guinea-pigs were compared with regard to their resistance to low pH, to hydrogen peroxide (H2O2) at different pH values and to superoxide (O2-). Low virulence was associated with susceptibility to H2O2 in native and isoniazid-resistant strains but not in laboratory-attenuated strain H37Ra. H2O2 resistance was only partly related to catalase content. Low virulence was not associated with susceptibility to an acid environment but the tuberculocidal effect of H2O2 was significantly increased at low pH. The strains were uniformly resistant to O2- and contained similar amounts of superoxide dismutase. The implications of these observations are discussed in the context of mechanisms of host defence in tuberculosis.", "contents": "Virulence and resistance to superoxide, low pH and hydrogen peroxide among strains of Mycobacterium tuberculosis. Six strains of Mycobacterium tuberculosis of different virulence in guinea-pigs were compared with regard to their resistance to low pH, to hydrogen peroxide (H2O2) at different pH values and to superoxide (O2-). Low virulence was associated with susceptibility to H2O2 in native and isoniazid-resistant strains but not in laboratory-attenuated strain H37Ra. H2O2 resistance was only partly related to catalase content. Low virulence was not associated with susceptibility to an acid environment but the tuberculocidal effect of H2O2 was significantly increased at low pH. The strains were uniformly resistant to O2- and contained similar amounts of superoxide dismutase. The implications of these observations are discussed in the context of mechanisms of host defence in tuberculosis."}
{"id": "PMID:24085", "title": "Exopolysaccharide production by Pseudomonas NCIB11264 grown in continuous culture.", "content": "Exopolysaccharide formation by Pseudomonas NCIB11264 in a single-stage continuous culture was maximal under nitrogen limitation with excess carbohydrate substrate at 30 +/- 1 degrees C and pH 7.0 +/- 0.1. Polysaccharide production was not enhanced by phosphate limitation but was dependent on the dilution rate. Steady states were maintained for up to 500 h without deterioration of the culture or the development of mutant strains. The efficiency of conversion of the glucose substrate utilized into exopolysaccharide by the chemostat cultures was as high as 73%.", "contents": "Exopolysaccharide production by Pseudomonas NCIB11264 grown in continuous culture. Exopolysaccharide formation by Pseudomonas NCIB11264 in a single-stage continuous culture was maximal under nitrogen limitation with excess carbohydrate substrate at 30 +/- 1 degrees C and pH 7.0 +/- 0.1. Polysaccharide production was not enhanced by phosphate limitation but was dependent on the dilution rate. Steady states were maintained for up to 500 h without deterioration of the culture or the development of mutant strains. The efficiency of conversion of the glucose substrate utilized into exopolysaccharide by the chemostat cultures was as high as 73%."}
{"id": "PMID:24090", "title": "Detection of a complex intermediate in the oxidation of ascorbic acid by the copper (II) ion.", "content": "A complex intermediate of the copper (II) ion with the ascorbate anion was detected by using a rapid scanning spectrophotometer with a stopped-flow apparatus. The intermediate was confirmed to be a copper (II) complex ion by electron paramagnetic resonance measurements. The dependence of the absorbance of the complex on the concentrations of reactants and on the pH of the reaction solutions indicates that the complex is Cu(II)Ha+ where Ha is the ascorbate anion ligand. The absorption maximum, the molar absorption coefficient, and the formation constant of the complex are 410 nm, 33 +/- 1 M-1 cm-1 at 420nm, and 42 +/- 6 M-1, respectively. The values are comparable to those in the other metal complexes of the ascorbate anion.", "contents": "Detection of a complex intermediate in the oxidation of ascorbic acid by the copper (II) ion. A complex intermediate of the copper (II) ion with the ascorbate anion was detected by using a rapid scanning spectrophotometer with a stopped-flow apparatus. The intermediate was confirmed to be a copper (II) complex ion by electron paramagnetic resonance measurements. The dependence of the absorbance of the complex on the concentrations of reactants and on the pH of the reaction solutions indicates that the complex is Cu(II)Ha+ where Ha is the ascorbate anion ligand. The absorption maximum, the molar absorption coefficient, and the formation constant of the complex are 410 nm, 33 +/- 1 M-1 cm-1 at 420nm, and 42 +/- 6 M-1, respectively. The values are comparable to those in the other metal complexes of the ascorbate anion."}
{"id": "PMID:24092", "title": "Salicylic acid fails to inhibit generation of thromboxane A2 activity in platelets after in vivo administration to the rat.", "content": "Arachidonic acid-induced aggregation of rat platelets and the accompanying generation of thromboxane A2 activity were inhibited by aspirin, whereas 20 times higher doses of salicylic, gentisic and salicyluric acids were inactive. Salicylic acid administered to the rats before aspirin prevented the inhibition of the cyclo-oxygenase-mediated effects of arachidonic acid. These results do not support the hypothesis that the anti-inflammatory activity of salicylic acid is due to inhibition of prostaglandin systhetase (cyclo-oxygenase) by an unknown metabolite and indicate that salicylic acid displays an anti-inflammatory activity independent inhibition of prostaglandin biosynthesis.", "contents": "Salicylic acid fails to inhibit generation of thromboxane A2 activity in platelets after in vivo administration to the rat. Arachidonic acid-induced aggregation of rat platelets and the accompanying generation of thromboxane A2 activity were inhibited by aspirin, whereas 20 times higher doses of salicylic, gentisic and salicyluric acids were inactive. Salicylic acid administered to the rats before aspirin prevented the inhibition of the cyclo-oxygenase-mediated effects of arachidonic acid. These results do not support the hypothesis that the anti-inflammatory activity of salicylic acid is due to inhibition of prostaglandin systhetase (cyclo-oxygenase) by an unknown metabolite and indicate that salicylic acid displays an anti-inflammatory activity independent inhibition of prostaglandin biosynthesis."}
{"id": "PMID:24093", "title": "Studies on the role of ACTH and of 5-HT in anxiety, using an animal model.", "content": "The effects of ACTH (5 & 7.5 microgram/100 g) were studied using a new animal model of anxiety. ACTH had an anxiogenic effect that was maximal during a 10 min test period starting 3 min after injection. The behavioural effects of ACTH were counteracted by chronic administration of chlordiazepoxide (5 mg kg-1 for 5 days) and by acute administration of ethanol (0.4 g kl-1). These anxiolytic drugs decreased the turnover of 5-HT in the midbrain, hypothalamus and cerebral cortex, whereas ACTH increased 5-HT turnover in the midbrain and hypothalamus. Is it therefore proposed that anxiety results from the action of ACTH, possibly on 5-HT pathways in the midbrain and hypothalamus.", "contents": "Studies on the role of ACTH and of 5-HT in anxiety, using an animal model. The effects of ACTH (5 & 7.5 microgram/100 g) were studied using a new animal model of anxiety. ACTH had an anxiogenic effect that was maximal during a 10 min test period starting 3 min after injection. The behavioural effects of ACTH were counteracted by chronic administration of chlordiazepoxide (5 mg kg-1 for 5 days) and by acute administration of ethanol (0.4 g kl-1). These anxiolytic drugs decreased the turnover of 5-HT in the midbrain, hypothalamus and cerebral cortex, whereas ACTH increased 5-HT turnover in the midbrain and hypothalamus. Is it therefore proposed that anxiety results from the action of ACTH, possibly on 5-HT pathways in the midbrain and hypothalamus."}
{"id": "PMID:24106", "title": "Problems associated with analysis and interpretation of small molecule/macromolecule binding data.", "content": "In the analysis of binding data, arbitrary transformations such as the Scatchard plot, may give misleading estimates of the binding parameters. The statistically correct approach is to determine values of K and n by non-linear regression of the actual dependent variable against the actual independent variable. In the case of the spectrophotometric titration method the dependent variable is the absorbance and the independent variable is the composition of the drug/macromolecule mixture. The method relies on an accurate estimate of the extinction coefficient of the bound drug and this is best treated as a parameter to be estimated in the regression analysis. In testing models by data fits alone it is emphasized that whilst a model may be rejected if it does not fit the data, a good fit does not ensure uniquieness and confirmatory, independent evidence must be sought.", "contents": "Problems associated with analysis and interpretation of small molecule/macromolecule binding data. In the analysis of binding data, arbitrary transformations such as the Scatchard plot, may give misleading estimates of the binding parameters. The statistically correct approach is to determine values of K and n by non-linear regression of the actual dependent variable against the actual independent variable. In the case of the spectrophotometric titration method the dependent variable is the absorbance and the independent variable is the composition of the drug/macromolecule mixture. The method relies on an accurate estimate of the extinction coefficient of the bound drug and this is best treated as a parameter to be estimated in the regression analysis. In testing models by data fits alone it is emphasized that whilst a model may be rejected if it does not fit the data, a good fit does not ensure uniquieness and confirmatory, independent evidence must be sought."}
{"id": "PMID:24107", "title": "The effect of drug concentration on the thermal (dark) degradation of promethazin hydrochloride in aqueous solution.", "content": "The thermal (dark) degradation of promethazine hydrochloride in aqueous solution presents a complex kinetic picture. The process is oxygen dependent and is modified by EDTA. In citrate buffer, pH 4.0, ionic strength 0.5M, containing 0.1% EDTA, the thermal degradation at 90 degrees can be fitted to first order rate plots at drug concentrations up to 1.56 x 10.27 (0.5%) and to zero order rate plots at drug concentrations greater than 9.35 x 10.2M (3.0%). At intermediate concentrations no simple equation can describe the data. These effects have been correlated with the formation of drug micelles and the rate date have been interpreted on the basis of a first order monomer process and a half order micellar process occurring simultaneously.", "contents": "The effect of drug concentration on the thermal (dark) degradation of promethazin hydrochloride in aqueous solution. The thermal (dark) degradation of promethazine hydrochloride in aqueous solution presents a complex kinetic picture. The process is oxygen dependent and is modified by EDTA. In citrate buffer, pH 4.0, ionic strength 0.5M, containing 0.1% EDTA, the thermal degradation at 90 degrees can be fitted to first order rate plots at drug concentrations up to 1.56 x 10.27 (0.5%) and to zero order rate plots at drug concentrations greater than 9.35 x 10.2M (3.0%). At intermediate concentrations no simple equation can describe the data. These effects have been correlated with the formation of drug micelles and the rate date have been interpreted on the basis of a first order monomer process and a half order micellar process occurring simultaneously."}
{"id": "PMID:24108", "title": "The determination of salicylic acid and benzoic acid in pharmaceutical formulations by spectrofluorimetry.", "content": "Methods of extraction from pharmaceutical formulations and subsequent determination of benzoic acid and salicylic acid by spectrofluorimetry are described. The recovery of benzoic acid, in the presence of salicylic acid, was 99.3%, with a coefficient of variation of 1.04%, while the recovery of salicylic acid, in the presence of benzoic acid, was 97.7%, with a coefficient of variation of 0-68%.", "contents": "The determination of salicylic acid and benzoic acid in pharmaceutical formulations by spectrofluorimetry. Methods of extraction from pharmaceutical formulations and subsequent determination of benzoic acid and salicylic acid by spectrofluorimetry are described. The recovery of benzoic acid, in the presence of salicylic acid, was 99.3%, with a coefficient of variation of 1.04%, while the recovery of salicylic acid, in the presence of benzoic acid, was 97.7%, with a coefficient of variation of 0-68%."}
{"id": "PMID:24109", "title": "Gastric erosions induced by analgesic drug mixtures in the rat.", "content": "Gastric erosions after oral administration of analgesics separately and in admixture have been examined in adult rats. After administration of acetylsalicylic acid (aspirin), phenacetin, paracetamol and caffeine as single drugs, gastric erosions were only observed with aspirin. The combination of aspirin with phenacetin did not change, that of aspirin with caffeine significantly increased, and aspirin with paracetamol significantly decreased the incidence of gastric lesions compared with aspirin alone. The results for aspirin with paracetamol did not differ from those for the vehicle. Addition of caffeine to the combination of aspirin and phenacetin caused a significant increase in erosions, but when given with aspirin and paracetamol no erosions occurred. The mechanisms underlying the effects of these drugs on aspirin-induced erosions are discussed.", "contents": "Gastric erosions induced by analgesic drug mixtures in the rat. Gastric erosions after oral administration of analgesics separately and in admixture have been examined in adult rats. After administration of acetylsalicylic acid (aspirin), phenacetin, paracetamol and caffeine as single drugs, gastric erosions were only observed with aspirin. The combination of aspirin with phenacetin did not change, that of aspirin with caffeine significantly increased, and aspirin with paracetamol significantly decreased the incidence of gastric lesions compared with aspirin alone. The results for aspirin with paracetamol did not differ from those for the vehicle. Addition of caffeine to the combination of aspirin and phenacetin caused a significant increase in erosions, but when given with aspirin and paracetamol no erosions occurred. The mechanisms underlying the effects of these drugs on aspirin-induced erosions are discussed."}
{"id": "PMID:24110", "title": "Effect of tolerance to morphine, ethanol and barbiturate on amphetamine circling in rats with a striatal dopamine lesion.", "content": "The (+)-amphetamine circling rate of rats with unilateral 6-OHDA lesions in the striatum was recorded. Morphine tablets were implanted subcutaneously for chronic treatment. In the morphine-dependent animal the circling rate to amphetamine given 4 days after morphine was first implanted was depressed but after withdrawal with naloxone a day later the rate increased, returning to normal after 21 days. Barbiturate physical dependence was induced by adding increasing amounts of barbitone to the drinking water of lesioned rats over four weeks after which the amphetamine circling response was depressed and remained so after the barbituate was withdrawn. Ethanol tolerance was induced by adding ethanol to the drinking water of lesioned rats for four weeks. Neither the induction of tolerance over this period nor ethanol withdrawal had any effect on the circling response to amphetamine. The change in the response of striatal dopamine neurons to amphetamine that occurs after chronic morphine treatment, cannot be produced by chronic treatment with either barbitone or ethanol. The neurochemical bases of barbiturate and ethanol tolerance are different from morphine tolerance.", "contents": "Effect of tolerance to morphine, ethanol and barbiturate on amphetamine circling in rats with a striatal dopamine lesion. The (+)-amphetamine circling rate of rats with unilateral 6-OHDA lesions in the striatum was recorded. Morphine tablets were implanted subcutaneously for chronic treatment. In the morphine-dependent animal the circling rate to amphetamine given 4 days after morphine was first implanted was depressed but after withdrawal with naloxone a day later the rate increased, returning to normal after 21 days. Barbiturate physical dependence was induced by adding increasing amounts of barbitone to the drinking water of lesioned rats over four weeks after which the amphetamine circling response was depressed and remained so after the barbituate was withdrawn. Ethanol tolerance was induced by adding ethanol to the drinking water of lesioned rats for four weeks. Neither the induction of tolerance over this period nor ethanol withdrawal had any effect on the circling response to amphetamine. The change in the response of striatal dopamine neurons to amphetamine that occurs after chronic morphine treatment, cannot be produced by chronic treatment with either barbitone or ethanol. The neurochemical bases of barbiturate and ethanol tolerance are different from morphine tolerance."}
{"id": "PMID:24111", "title": "Effects of bromocriptine on adenylate cyclase and phosphodiesterase activities of rat striatum.", "content": "The activity of 2-bromo-alpha-ergokryptine (bromocriptine) (5 mg kg-1, i.p.) on adenylate cyclase and on phosphodiesterase (PDE-PDE II) of rat striatum, has been examined both in vitro and in vivo. In vitro and in vivo bromocriptine stimulated adenylate cyclase activity, but reduced the stimulating effect of dopamine on adenylate cyclase activity. Bromocriptine showed a dose-dependent biphasic action on phosphodiesterases in vitro while in vivo it stimulated them. The results obtained proved bromocriptine to have an agonist-antagonist action at striatal dopamine receptor level, with a relevant effect on the cAMP system.", "contents": "Effects of bromocriptine on adenylate cyclase and phosphodiesterase activities of rat striatum. The activity of 2-bromo-alpha-ergokryptine (bromocriptine) (5 mg kg-1, i.p.) on adenylate cyclase and on phosphodiesterase (PDE-PDE II) of rat striatum, has been examined both in vitro and in vivo. In vitro and in vivo bromocriptine stimulated adenylate cyclase activity, but reduced the stimulating effect of dopamine on adenylate cyclase activity. Bromocriptine showed a dose-dependent biphasic action on phosphodiesterases in vitro while in vivo it stimulated them. The results obtained proved bromocriptine to have an agonist-antagonist action at striatal dopamine receptor level, with a relevant effect on the cAMP system."}
{"id": "PMID:24112", "title": "A comparison of the binding constant (KD) of 125I-labelled 3-(4-iodophenoxy)-1-isopropylamino-propan-2-ol obtained on beta-adrenoceptors in guinea-pig myocardial membranes, with its dissociation constants (KB) obtained on guinea-pig isolated atria and trachea.", "content": "The dissociation constant of binding (KD) of 125I-labelled 3-(4-iodophenoxy)-1-isoproplyaminopropan-2-ol (IIP) to guinea-pig myocardial membrane preparations was 2.2 x 10-8M. In pharmacological experiments with the non-labelled material and 60 min contact time, IIP produced a parallel shift in the orciprenaline concentration-response line on guinea-pig isolated tracheal and atrial preparations. The dissociation constant (KB) of IIP was 2.9 x 10-8M on atria (pA2 7.54) and 3.3 x 10-8M on trachea (pA2 7-48). These values indicate that IIP is not a selective beta-adrenoceptor blocking drug. In addition, agreement was found between the affinity constant of this antagonist for beta-adrenoceptors as determined by a direct binding study and an indirect pharmacological study.", "contents": "A comparison of the binding constant (KD) of 125I-labelled 3-(4-iodophenoxy)-1-isopropylamino-propan-2-ol obtained on beta-adrenoceptors in guinea-pig myocardial membranes, with its dissociation constants (KB) obtained on guinea-pig isolated atria and trachea. The dissociation constant of binding (KD) of 125I-labelled 3-(4-iodophenoxy)-1-isoproplyaminopropan-2-ol (IIP) to guinea-pig myocardial membrane preparations was 2.2 x 10-8M. In pharmacological experiments with the non-labelled material and 60 min contact time, IIP produced a parallel shift in the orciprenaline concentration-response line on guinea-pig isolated tracheal and atrial preparations. The dissociation constant (KB) of IIP was 2.9 x 10-8M on atria (pA2 7.54) and 3.3 x 10-8M on trachea (pA2 7-48). These values indicate that IIP is not a selective beta-adrenoceptor blocking drug. In addition, agreement was found between the affinity constant of this antagonist for beta-adrenoceptors as determined by a direct binding study and an indirect pharmacological study."}
{"id": "PMID:24114", "title": "Inhibition of hydrochloric acid and pepsin secretion from gastric pouches by antral pouch acidification in sheep.", "content": "1. Secretion of acid and pepsin from separated pouches of the body of the abomasum was studied in sheep during perfusion of antral pouches with acid solutions. 2. Resting secretion of acid and pepsin was reduced by acidification of antral pouches to pH 2.7 or less. 3. Increases in the secretion of HCl and pepsin normally obtained on feeding were reduced or abolished by perfusion of antral pouches with solutions at pH 1.3--2.0. 4. Perfusion of antral pouches with acetylcholine at pH 2.5 failed to stimulate acid secretion as it did at a higher pH. 5. Pentagastrin stimulated acid and pepsin secretion during the inhibition of secretion produced by antral pouch acidification. 6. Increases in reticular motility occurred on antral pouch acidification with solutions of pH 1.1--1.3. 7. The contribution of antral pH in regulating abomasal acid secretion is discussed.", "contents": "Inhibition of hydrochloric acid and pepsin secretion from gastric pouches by antral pouch acidification in sheep. 1. Secretion of acid and pepsin from separated pouches of the body of the abomasum was studied in sheep during perfusion of antral pouches with acid solutions. 2. Resting secretion of acid and pepsin was reduced by acidification of antral pouches to pH 2.7 or less. 3. Increases in the secretion of HCl and pepsin normally obtained on feeding were reduced or abolished by perfusion of antral pouches with solutions at pH 1.3--2.0. 4. Perfusion of antral pouches with acetylcholine at pH 2.5 failed to stimulate acid secretion as it did at a higher pH. 5. Pentagastrin stimulated acid and pepsin secretion during the inhibition of secretion produced by antral pouch acidification. 6. Increases in reticular motility occurred on antral pouch acidification with solutions of pH 1.1--1.3. 7. The contribution of antral pH in regulating abomasal acid secretion is discussed."}
{"id": "PMID:24115", "title": "Osmotic behaviour of human red blood cells: an interpretation in terms of negative intracellular fluid pressure.", "content": "1. The observation that human red blood cells do not shrink in hypertonic media as much as expected for ideal osmometers has previously been explained in terms of either a marked increase in the osmotic coefficient of the cell contents or an increase in the chloride content of the cells.2. Changes in suspension pH and haematocrit have been observed when the concentration of the unbuffered NaCl medium was doubled. The small increases in external pH, and the size of the volume decreases, are inconsistent with variations in the Cl content as a significant factor in the non-ideal osmotic responses.3. Membrane potentials of red cells in buffered media were followed using the fluorescent dye, diS-C(3)-(5). On shrinking at pH 7.4, the cells hyperpolarized ca. 5 mV as predicted if changes in the osmotic coefficient rather than in Cl content explained the osmotic behaviour.4. Regarding haemoglobin in concentrated solution as a solute with high osmotic coefficient is formally correct but is little help in understanding the properties of the solution. We have found it useful to consider separately haemoglobin and the rest of the contents of the cell. The haemoglobin then supports part of the total hydrostatic pressure on the cell leaving the crystalloid solution to experience a reduced fluid pressure. In greatly shrunken cells the contents act like a gel with the matrix of haemoglobin under compression and the fluid which fills the spaces within the matrix under tension.", "contents": "Osmotic behaviour of human red blood cells: an interpretation in terms of negative intracellular fluid pressure. 1. The observation that human red blood cells do not shrink in hypertonic media as much as expected for ideal osmometers has previously been explained in terms of either a marked increase in the osmotic coefficient of the cell contents or an increase in the chloride content of the cells.2. Changes in suspension pH and haematocrit have been observed when the concentration of the unbuffered NaCl medium was doubled. The small increases in external pH, and the size of the volume decreases, are inconsistent with variations in the Cl content as a significant factor in the non-ideal osmotic responses.3. Membrane potentials of red cells in buffered media were followed using the fluorescent dye, diS-C(3)-(5). On shrinking at pH 7.4, the cells hyperpolarized ca. 5 mV as predicted if changes in the osmotic coefficient rather than in Cl content explained the osmotic behaviour.4. Regarding haemoglobin in concentrated solution as a solute with high osmotic coefficient is formally correct but is little help in understanding the properties of the solution. We have found it useful to consider separately haemoglobin and the rest of the contents of the cell. The haemoglobin then supports part of the total hydrostatic pressure on the cell leaving the crystalloid solution to experience a reduced fluid pressure. In greatly shrunken cells the contents act like a gel with the matrix of haemoglobin under compression and the fluid which fills the spaces within the matrix under tension."}
{"id": "PMID:24116", "title": "Effects of adrenoceptor stimulating and blocking agents on carotid body chemosensory inhibition.", "content": "1. The effects of alpha- and beta-adrenoceptor agonists and antagonists on chemosensory discharges originating from carotid bodies in situ were studied in anaesthetized cats.2. Noradrenaline (NA) injections commonly resulted in increased frequency of carotid nerve chemosensory discharge, an effect ascribed to reduced blood flow through the glomus, and reduced or eliminated by alpha-adrenergic block.3. NA injections occasionally produced an initial reduction of chemosensory discharge frequency, which was however less intense and of shorter duration than that caused by dopamine. This effect of NA is not mediated by alpha-adrenoceptors, since it is not blocked by dibenamine, but probably by low affinity for dopamine receptors.4. Dopamine and apomorphine-elicited chemosensory inhibition were not affected by low doses of phenoxybenzamine, which blocked NA-evoked hypertensive reactions.5. Higher doses of phenoxybenzamine and dibenamine produced a displacement to the right of dose-response curves for dopamine- and apormorphine-elicited chemosensory inhibition. However, this interference by alpha-adrenergic blockers was attributed to the resultant hypotension, since it was reversed upon restoration of blood pressure.6. Isoprenaline, a beta-adrenergic agonist, did not induce chemosensory inhibition, whilst beta-adrenergic blockers (propranolol and dichloroisoproterenol) did not modify dopamine- and apomorphine-elicited chemosensory inhibition.7. These results provide further support for the hypothesis that chemosensory inhibition could be mediated by specific dopamine receptors, distinct from alpha- and beta-adrenoceptors.", "contents": "Effects of adrenoceptor stimulating and blocking agents on carotid body chemosensory inhibition. 1. The effects of alpha- and beta-adrenoceptor agonists and antagonists on chemosensory discharges originating from carotid bodies in situ were studied in anaesthetized cats.2. Noradrenaline (NA) injections commonly resulted in increased frequency of carotid nerve chemosensory discharge, an effect ascribed to reduced blood flow through the glomus, and reduced or eliminated by alpha-adrenergic block.3. NA injections occasionally produced an initial reduction of chemosensory discharge frequency, which was however less intense and of shorter duration than that caused by dopamine. This effect of NA is not mediated by alpha-adrenoceptors, since it is not blocked by dibenamine, but probably by low affinity for dopamine receptors.4. Dopamine and apomorphine-elicited chemosensory inhibition were not affected by low doses of phenoxybenzamine, which blocked NA-evoked hypertensive reactions.5. Higher doses of phenoxybenzamine and dibenamine produced a displacement to the right of dose-response curves for dopamine- and apormorphine-elicited chemosensory inhibition. However, this interference by alpha-adrenergic blockers was attributed to the resultant hypotension, since it was reversed upon restoration of blood pressure.6. Isoprenaline, a beta-adrenergic agonist, did not induce chemosensory inhibition, whilst beta-adrenergic blockers (propranolol and dichloroisoproterenol) did not modify dopamine- and apomorphine-elicited chemosensory inhibition.7. These results provide further support for the hypothesis that chemosensory inhibition could be mediated by specific dopamine receptors, distinct from alpha- and beta-adrenoceptors."}
{"id": "PMID:24120", "title": "Acid secretion and intracellular pH in isolated oxyntic cells.", "content": "This study demonstrates that isolated oxyntic cells are capable of secreting hydrochloric acid. Transitory peaks of medium acidification were observed when isolated oxyntic cells were stimulated with diffferent secretagogues. The duration of these peaks was of about 3 min and had a magnitude of about 0.5 muEquiv/hr mg dry weight. These peaks were abolished by selective inhibitors of acid secretion and/or secretagogue action. Cell pH, as measured by the DMO14C technique increases 0.13 pH units upon stimulation with db-cAMP. This change was abolished by pretreatment with SCN-. From acidification and cell pH experiments an increase of 5-10mM in base concentration inside the cell upon stimulation is calculated. These results are interpreted on the basis of the existence of a neutral anion exchange mechanism at the serosal side that serves to control the cell acid-base balance.", "contents": "Acid secretion and intracellular pH in isolated oxyntic cells. This study demonstrates that isolated oxyntic cells are capable of secreting hydrochloric acid. Transitory peaks of medium acidification were observed when isolated oxyntic cells were stimulated with diffferent secretagogues. The duration of these peaks was of about 3 min and had a magnitude of about 0.5 muEquiv/hr mg dry weight. These peaks were abolished by selective inhibitors of acid secretion and/or secretagogue action. Cell pH, as measured by the DMO14C technique increases 0.13 pH units upon stimulation with db-cAMP. This change was abolished by pretreatment with SCN-. From acidification and cell pH experiments an increase of 5-10mM in base concentration inside the cell upon stimulation is calculated. These results are interpreted on the basis of the existence of a neutral anion exchange mechanism at the serosal side that serves to control the cell acid-base balance."}
{"id": "PMID:24121", "title": "Transport of heterocyclic acids across rat small intestine in vitro.", "content": "A study has been made of the steady-state fluxes of barbituric acid, six of its substituted derivatives, and 5,5-dimethyloxazolidinedione (DMO) across the wall of rat jejunum in vitro. For each of the compounds tested the mucosal (M) to serosal (S) flux was significantly larger than the S to M flux. Both M to S and S to M fluxes increased linearly with concentration, and the transport of one acid was not influenced by the presence of a tenfold greater concentration of a second heterocyclic acid. The fluxes decreased as the pH of the incubation saline was increased, but neither the M to S, nor the S to M fluxes could be described in terms of simple nonionic diffusion. It was found that the relation between the flux ratios of the transported acids and their pKalpha values could be described by an equation derived from consideration of the transport of a weak acid in a series three compartment system, and it has been concluded that the three compartment system provides a good working hypothesis for the mechanism of heterocyclic acid transport across rat jejunum. It was found that the best fit of the theoretical curve to the experimental data was obtained when the ratio of permeabilities to the ionized and nonionized forms of a weak acid at one of the barriers was assigned the value 5 X 10(-1). It is suggested that this value may be characteristic of a noncellular restriction to diffusion, such as a layer of connective tissue, and substantiates previous suggestions that the intermediate compartment of the intestinal three compartment system is a component of the sub-epithelial extracellular space.", "contents": "Transport of heterocyclic acids across rat small intestine in vitro. A study has been made of the steady-state fluxes of barbituric acid, six of its substituted derivatives, and 5,5-dimethyloxazolidinedione (DMO) across the wall of rat jejunum in vitro. For each of the compounds tested the mucosal (M) to serosal (S) flux was significantly larger than the S to M flux. Both M to S and S to M fluxes increased linearly with concentration, and the transport of one acid was not influenced by the presence of a tenfold greater concentration of a second heterocyclic acid. The fluxes decreased as the pH of the incubation saline was increased, but neither the M to S, nor the S to M fluxes could be described in terms of simple nonionic diffusion. It was found that the relation between the flux ratios of the transported acids and their pKalpha values could be described by an equation derived from consideration of the transport of a weak acid in a series three compartment system, and it has been concluded that the three compartment system provides a good working hypothesis for the mechanism of heterocyclic acid transport across rat jejunum. It was found that the best fit of the theoretical curve to the experimental data was obtained when the ratio of permeabilities to the ionized and nonionized forms of a weak acid at one of the barriers was assigned the value 5 X 10(-1). It is suggested that this value may be characteristic of a noncellular restriction to diffusion, such as a layer of connective tissue, and substantiates previous suggestions that the intermediate compartment of the intestinal three compartment system is a component of the sub-epithelial extracellular space."}
{"id": "PMID:24124", "title": "Deoxypyrimidine nucleoside metabolism in varicella-zoster virus-infected cells.", "content": "Noninfected and varicella-zoster virus (VZV)-infected human foreskin fibroblasts were examined for thymidine kinase activity. The specific activity of VZV-infected cell extracts was approximately 7.5-fold greater than that of mock-infected cells and 3-fold greater than that of actively growing cells. The pH optimum of VZV-infected cell thymidine kinase activity was found to be 8.0, whereas thymidine kinase activity in noninfected cells exhibited a sharp pH optimum at 7.4. Electrophoretic analysis of cellular enzymes involved in pyrimidine nucleoside phosphorylation revealed at least three enzymes distinguishable by electrophoretic mobility and substrates used. These enzymes were presumed to be thymidine kinase, deoxycytidine kinase, and uridine kinase. The relative mobilities of these enzymes on 5% polyacrylamide gels were 0.18, 0.91, and 0.54, respectively. In VZV-infected cells, a single band of activity catalyzing the phosphorylation of thymidine, deoxyuridine, deoxycytidine, and cytidine was observed with a relative mobility of 0.48. Cellular pyrimidine-phosphorylating enzymes were not detected in VZV-infected cells. The molecular weight of the VZV-induced enzyme was determined to be 72,000 +/- 7%.", "contents": "Deoxypyrimidine nucleoside metabolism in varicella-zoster virus-infected cells. Noninfected and varicella-zoster virus (VZV)-infected human foreskin fibroblasts were examined for thymidine kinase activity. The specific activity of VZV-infected cell extracts was approximately 7.5-fold greater than that of mock-infected cells and 3-fold greater than that of actively growing cells. The pH optimum of VZV-infected cell thymidine kinase activity was found to be 8.0, whereas thymidine kinase activity in noninfected cells exhibited a sharp pH optimum at 7.4. Electrophoretic analysis of cellular enzymes involved in pyrimidine nucleoside phosphorylation revealed at least three enzymes distinguishable by electrophoretic mobility and substrates used. These enzymes were presumed to be thymidine kinase, deoxycytidine kinase, and uridine kinase. The relative mobilities of these enzymes on 5% polyacrylamide gels were 0.18, 0.91, and 0.54, respectively. In VZV-infected cells, a single band of activity catalyzing the phosphorylation of thymidine, deoxyuridine, deoxycytidine, and cytidine was observed with a relative mobility of 0.48. Cellular pyrimidine-phosphorylating enzymes were not detected in VZV-infected cells. The molecular weight of the VZV-induced enzyme was determined to be 72,000 +/- 7%."}
{"id": "PMID:24125", "title": "Protein kinase from avian myeloblastosis virus.", "content": "A protein kinase associated with purified virions of avian myeloblastosis BAI strain A was partially purified by ion-exchange chromatography and gel filtration. The transfer of phosphate catalyzed by this enzyme required a divalent metal ion and ATP as phosphate donor. GTP could not be substituted for ATP, and the reaction was unaffected by either cyclic AMP or beef-heart protein-kinase inhibitor. Of the virus and nonvirus proteins tested as phosphate acceptors, only acidic proteins were phosphorylated. In particular, purified preparations of reverse transcriptase from avian myeloblastosis virus did not accept phosphate. The enzyme is a basic protein (pI = 9.3), and, on the basis of molecular sieving through Sephadex G-200 and velocity sedimentation on glycerol gradient, the protein kinase has a molecular weight of 45,000.", "contents": "Protein kinase from avian myeloblastosis virus. A protein kinase associated with purified virions of avian myeloblastosis BAI strain A was partially purified by ion-exchange chromatography and gel filtration. The transfer of phosphate catalyzed by this enzyme required a divalent metal ion and ATP as phosphate donor. GTP could not be substituted for ATP, and the reaction was unaffected by either cyclic AMP or beef-heart protein-kinase inhibitor. Of the virus and nonvirus proteins tested as phosphate acceptors, only acidic proteins were phosphorylated. In particular, purified preparations of reverse transcriptase from avian myeloblastosis virus did not accept phosphate. The enzyme is a basic protein (pI = 9.3), and, on the basis of molecular sieving through Sephadex G-200 and velocity sedimentation on glycerol gradient, the protein kinase has a molecular weight of 45,000."}
{"id": "PMID:24127", "title": "Increased lysyl oxidase activity in blood vessels of hypertensive rats and effect of beta-aminopropionitrile on arteriosclerosis.", "content": "The activity of lysyl oxidase which catalyzes the initial step of cross-linking of collagen and elastin polypeptides was measured in blood vessels of the hypertensive rat. The enzyme activity was increased in the aorta and mesenteric artery when hypertension was induced in 8-week-old rats with administration of deoxycorticosterone acetate (DOCA) and 1% saline. Reserpine diminished this increase in vascular lysyl oxidase activity concomitant with reduction in blood pressure. When beta-aminopropionitrile, a specific inhibitor of lysyl oxidase, was administered before the onset of DOCA-salt hypertension, the aortic collagen content was reduced markedly. Concomitant with reduction in the aortic collagen content, the development of hypertension and arteriosclerotic changes in the kidney was partially prevented. These results would indicate that hypertension increases the amount and the degree of cross-linking of vascular collagen and that the deposition of excess collagen in the vascular wall contributes to the development of hypertension and arteriosclerosis.", "contents": "Increased lysyl oxidase activity in blood vessels of hypertensive rats and effect of beta-aminopropionitrile on arteriosclerosis. The activity of lysyl oxidase which catalyzes the initial step of cross-linking of collagen and elastin polypeptides was measured in blood vessels of the hypertensive rat. The enzyme activity was increased in the aorta and mesenteric artery when hypertension was induced in 8-week-old rats with administration of deoxycorticosterone acetate (DOCA) and 1% saline. Reserpine diminished this increase in vascular lysyl oxidase activity concomitant with reduction in blood pressure. When beta-aminopropionitrile, a specific inhibitor of lysyl oxidase, was administered before the onset of DOCA-salt hypertension, the aortic collagen content was reduced markedly. Concomitant with reduction in the aortic collagen content, the development of hypertension and arteriosclerotic changes in the kidney was partially prevented. These results would indicate that hypertension increases the amount and the degree of cross-linking of vascular collagen and that the deposition of excess collagen in the vascular wall contributes to the development of hypertension and arteriosclerosis."}
{"id": "PMID:24130", "title": "Pathogenicity of a vaccine strain of vaccina virus in rabbits administered by intravenous route.", "content": "The pathogenicity of the Lister (Elstree) strain, a vaccinia virus, in rabbits after intravenous injection was studied by histopathological and immunofluorescent methods. Inoculation of 1 X 10(7) PFU (pock-forming unit) virus into weanling and young adult rabbits caused severe emaciation and high mortality within 2 weeks. Pathological findings were characterized by vesicular lesions along muco-cutaneous junction areas of the eyes, nose and mouth and by inflammatory changes in the brain, mainly in the meninges and choroid plexus. Immunofluorescent staining of the tissues of animals sacrificed at intervals demonstrated the accumulation of vaccinia viral antigen (s) in the loci of pathological changes. The suitability of this model system for the study of pathogenesis of human postvaccinal meningoencephalitis is discussed.", "contents": "Pathogenicity of a vaccine strain of vaccina virus in rabbits administered by intravenous route. The pathogenicity of the Lister (Elstree) strain, a vaccinia virus, in rabbits after intravenous injection was studied by histopathological and immunofluorescent methods. Inoculation of 1 X 10(7) PFU (pock-forming unit) virus into weanling and young adult rabbits caused severe emaciation and high mortality within 2 weeks. Pathological findings were characterized by vesicular lesions along muco-cutaneous junction areas of the eyes, nose and mouth and by inflammatory changes in the brain, mainly in the meninges and choroid plexus. Immunofluorescent staining of the tissues of animals sacrificed at intervals demonstrated the accumulation of vaccinia viral antigen (s) in the loci of pathological changes. The suitability of this model system for the study of pathogenesis of human postvaccinal meningoencephalitis is discussed."}
{"id": "PMID:24132", "title": "Correction of hyperkalemia by bicarbonate despite constant blood pH.", "content": "Patients having hyperkalemia often are given bicarbonate to raise blood pH and shift extracellular potassium into cells. Blood pH in many hyperkalemic patients, however, is compensated. To determine whether bicarbonate, independent of its pH action, affects plasma potassium, 14 hyperkalemic patients were treated with bicarbonate in 5% dextrose. In five patients (changed pH group), blood pH rose at least 0.08, while in nine (constant pH group), it changed less than 0.04. In the first group, pH rose 0.12, bicarbonate rose 5.9 mEq/liter, and plasma potassium fell 1.6 mEq/liter, and plasma potassium fell 1.4 mEq/liter. The correlation between changes in plasma potassium and bicarbonate was identical in the two groups and independent of urinary potassium excretion. Four additional patients, who were treated with 5% dextrose alone, did not significantly lower their plasma potassium, although subsequent treatment with bicarbonate in 5% dextrose lowered their plasma potassium. Thus, bicarbonate lowers plasma potassium, independent of its effect on blood pH, and despite a risk of volume overload, should be used to treat hyperkalemia in compensated acid-base disorders, even in the presence of renal failure, provided the plasma bicarbonate concentration is decreased.", "contents": "Correction of hyperkalemia by bicarbonate despite constant blood pH. Patients having hyperkalemia often are given bicarbonate to raise blood pH and shift extracellular potassium into cells. Blood pH in many hyperkalemic patients, however, is compensated. To determine whether bicarbonate, independent of its pH action, affects plasma potassium, 14 hyperkalemic patients were treated with bicarbonate in 5% dextrose. In five patients (changed pH group), blood pH rose at least 0.08, while in nine (constant pH group), it changed less than 0.04. In the first group, pH rose 0.12, bicarbonate rose 5.9 mEq/liter, and plasma potassium fell 1.6 mEq/liter, and plasma potassium fell 1.4 mEq/liter. The correlation between changes in plasma potassium and bicarbonate was identical in the two groups and independent of urinary potassium excretion. Four additional patients, who were treated with 5% dextrose alone, did not significantly lower their plasma potassium, although subsequent treatment with bicarbonate in 5% dextrose lowered their plasma potassium. Thus, bicarbonate lowers plasma potassium, independent of its effect on blood pH, and despite a risk of volume overload, should be used to treat hyperkalemia in compensated acid-base disorders, even in the presence of renal failure, provided the plasma bicarbonate concentration is decreased."}
{"id": "PMID:24139", "title": "Localization of some glycolipid glycosylating enzymes in the Golgi apparatus of rat kidney.", "content": "Cell fractions from rat kidney were isolated and studied for their ability to synthesize several possible intermediates in the biosynthesis of sulfatides and gangliosides. The enzymes studied include UDP-Gal:ceramide galactosyltransferase, UDP-Gal:glucosylceramide galactosyltransferase, UDP-Gal:galactosylceramide galactosyltransferase, and CMP-NAN:lactosylceramide sialytransferase activities. The initial glycosylation of ceramide was found to be present in all of the kidney cell fractions studied. The remaining glycosylating enzymes were largely localized in the Golgi apparatus of kidney. Thus, in addition to modifying glycoproteins for secretion, the Golgi apparatus in kidney is involved in the modification of a number of glycolipids which are destined to form cell membrane components.", "contents": "Localization of some glycolipid glycosylating enzymes in the Golgi apparatus of rat kidney. Cell fractions from rat kidney were isolated and studied for their ability to synthesize several possible intermediates in the biosynthesis of sulfatides and gangliosides. The enzymes studied include UDP-Gal:ceramide galactosyltransferase, UDP-Gal:glucosylceramide galactosyltransferase, UDP-Gal:galactosylceramide galactosyltransferase, and CMP-NAN:lactosylceramide sialytransferase activities. The initial glycosylation of ceramide was found to be present in all of the kidney cell fractions studied. The remaining glycosylating enzymes were largely localized in the Golgi apparatus of kidney. Thus, in addition to modifying glycoproteins for secretion, the Golgi apparatus in kidney is involved in the modification of a number of glycolipids which are destined to form cell membrane components."}
{"id": "PMID:24143", "title": "[Classical and modified intramedullary nailing in osteomyelitis pseudoarthroses].", "content": "13 cases of osteomyelitic pseudarthroses following injury were treated by the authors, by means of intramedullary nailing. 5 of these patients already cured are introduced in detail in the article. Intramedullary nailing in the classic manner and its modification, using bolts as well, were performed alike. The authors have a favourable impression after these series. No septic complication occured. Intramedullary nailing is a good method in the management of this serious sequel to fracture treatment.", "contents": "[Classical and modified intramedullary nailing in osteomyelitis pseudoarthroses]. 13 cases of osteomyelitic pseudarthroses following injury were treated by the authors, by means of intramedullary nailing. 5 of these patients already cured are introduced in detail in the article. Intramedullary nailing in the classic manner and its modification, using bolts as well, were performed alike. The authors have a favourable impression after these series. No septic complication occured. Intramedullary nailing is a good method in the management of this serious sequel to fracture treatment."}
{"id": "PMID:24144", "title": "[Experience in the treatment of peripheral vascular injuries].", "content": "The authors report the results of the treatment of injuries to the peripheral blood vessels that were observed at the Semmelweis OTE in 16 years. As a result of primary operative treatment the peripheral pulse returned to the injured limb in 10 cases. A quick diagnosis and instant reconstructive surgery is absolutely necessary. Mistakes and complications in the treatment are listed in this paper, based on the own experiences of the authors. The authors stress that these complications should be recognized in time and be treated properly.", "contents": "[Experience in the treatment of peripheral vascular injuries]. The authors report the results of the treatment of injuries to the peripheral blood vessels that were observed at the Semmelweis OTE in 16 years. As a result of primary operative treatment the peripheral pulse returned to the injured limb in 10 cases. A quick diagnosis and instant reconstructive surgery is absolutely necessary. Mistakes and complications in the treatment are listed in this paper, based on the own experiences of the authors. The authors stress that these complications should be recognized in time and be treated properly."}
{"id": "PMID:24145", "title": "[Congenital knee luxation].", "content": "The authors discuss the frequency, etiology, symptoms and classification as well as treatment of congenital dislocation of the knee. 8 own cases are reported in the article. The authors suggest that congenital dislocation of the may be well influenced by non-operative methods. Etappe redressement by means of plaster does not interfere with the functional treatment of the hip dislocation usually treated with the Pavlik braces. Associated foot deformities may be easily corrected at the same time. The so called \"earliest treatment\" is most important in all the three deformities (knee-hip dislocation, club foot), the authors emphasise.", "contents": "[Congenital knee luxation]. The authors discuss the frequency, etiology, symptoms and classification as well as treatment of congenital dislocation of the knee. 8 own cases are reported in the article. The authors suggest that congenital dislocation of the may be well influenced by non-operative methods. Etappe redressement by means of plaster does not interfere with the functional treatment of the hip dislocation usually treated with the Pavlik braces. Associated foot deformities may be easily corrected at the same time. The so called \"earliest treatment\" is most important in all the three deformities (knee-hip dislocation, club foot), the authors emphasise."}
{"id": "PMID:24146", "title": "[Evaluation of operations on discoid meniscus].", "content": "A short survey of literature is given in the article. 1480 meniscectomies were performed at the Orthopedic Clinic of Semmelweis Medical University in the interval between 1952--75; 29 of these cases were carried out for discoid menisci. Symptoms are introduced and results of operative treatment are evaluated. The author makes a few suggestions based on his own experiences.", "contents": "[Evaluation of operations on discoid meniscus]. A short survey of literature is given in the article. 1480 meniscectomies were performed at the Orthopedic Clinic of Semmelweis Medical University in the interval between 1952--75; 29 of these cases were carried out for discoid menisci. Symptoms are introduced and results of operative treatment are evaluated. The author makes a few suggestions based on his own experiences."}
{"id": "PMID:24147", "title": "[Treatment of hand injuries on the principle of \"delayed emergency\"].", "content": "A certain number of drunk patients who suffered hand injury were not prone to operation on the day of admission, as usual, for different reasons (behaviour of the patient etc.). These patients were treated on the delayed urgency principle, that Iselin worked out. Results in the 266 cases were surprisingly good. There were much less complications with this method, compared to previous results achieved when primary treatment of wounds was practised. Yet more experience is necessary, to work out certain details and more exact indications, the authors state.", "contents": "[Treatment of hand injuries on the principle of \"delayed emergency\"]. A certain number of drunk patients who suffered hand injury were not prone to operation on the day of admission, as usual, for different reasons (behaviour of the patient etc.). These patients were treated on the delayed urgency principle, that Iselin worked out. Results in the 266 cases were surprisingly good. There were much less complications with this method, compared to previous results achieved when primary treatment of wounds was practised. Yet more experience is necessary, to work out certain details and more exact indications, the authors state."}
{"id": "PMID:24148", "title": "[Spontaneous rupture of the extensor pollicis longus tendon].", "content": "A rare case of \"spontaneous\" rupture of the extensor pollicis longus tendon with primary chronic polyarthritis in the background is reported in this paper. In this case a transposition of the extensor indicis proprius was carried out, with the modification by J. B\u00f6hler and Manninger. This method gives a very good functional result.", "contents": "[Spontaneous rupture of the extensor pollicis longus tendon]. A rare case of \"spontaneous\" rupture of the extensor pollicis longus tendon with primary chronic polyarthritis in the background is reported in this paper. In this case a transposition of the extensor indicis proprius was carried out, with the modification by J. B\u00f6hler and Manninger. This method gives a very good functional result."}
{"id": "PMID:24149", "title": "[2 cases of congenital humero-radial synostosis].", "content": "Two cases of a rare congenital deformity, humeroradial aplasia are reported in the article. In the first case the deformity was unilateral, in the second case a bilateral aplasia was associated to hip dislocation and aplasia of the os ischii.", "contents": "[2 cases of congenital humero-radial synostosis]. Two cases of a rare congenital deformity, humeroradial aplasia are reported in the article. In the first case the deformity was unilateral, in the second case a bilateral aplasia was associated to hip dislocation and aplasia of the os ischii."}
{"id": "PMID:24150", "title": "[Double gunshot head injury with lesion of the upper cervical vertebrae in a case of attempted suicide].", "content": "The authors hold their case reported in this paper interesting for the following reasons: in several minutes two shots were fired by intention of suicide. Two entrance openings were found that had the characteristics of shots fired within close range, but no exit openings were to be seen. Considering the entrance openings, the bilateral fracture of the atlas and a comminuted unilateral fracture of the axis and spotting the jammed missiles inside the tunnel, one must deduce that the missiles went by vital structures without severing them.", "contents": "[Double gunshot head injury with lesion of the upper cervical vertebrae in a case of attempted suicide]. The authors hold their case reported in this paper interesting for the following reasons: in several minutes two shots were fired by intention of suicide. Two entrance openings were found that had the characteristics of shots fired within close range, but no exit openings were to be seen. Considering the entrance openings, the bilateral fracture of the atlas and a comminuted unilateral fracture of the axis and spotting the jammed missiles inside the tunnel, one must deduce that the missiles went by vital structures without severing them."}
{"id": "PMID:24151", "title": "[Surgical correction of a case of congenital proximal radio-ulnar synostosis].", "content": "The author reports a case of S.R.U.P.C. that was relieved by a Nigrisoli operation. There is a good function after two years. The author thought it worth publishing this cae because of its rarity: in the last twenty years only one article appeared on this problem in the Rumanian medical literature that reported 5 cases.", "contents": "[Surgical correction of a case of congenital proximal radio-ulnar synostosis]. The author reports a case of S.R.U.P.C. that was relieved by a Nigrisoli operation. There is a good function after two years. The author thought it worth publishing this cae because of its rarity: in the last twenty years only one article appeared on this problem in the Rumanian medical literature that reported 5 cases."}
{"id": "PMID:24152", "title": "[A case of open carpo-metacarpal dislocation complicated by dislocation of the trapezoid bone].", "content": "A case of open carpo-metacarpal dislocation complicated by dislocation of the os trapesium is reported in this paper. The patient's wrist healed with good functional results, despite a partial mistake in diagnosis. The authors draw attention to the fact, that X-ray films taken at admission must be analysed carefully and intraoperative X-rays films must be taken. By demonstration their own mistake in diagnosis and treatment, the authors hope that a similar mistake will be avoided. Following early open or closed reduction, a temporary wire fixation of the metacarpal bones to the carpal bones is recommended in order to prevent redislocation.", "contents": "[A case of open carpo-metacarpal dislocation complicated by dislocation of the trapezoid bone]. A case of open carpo-metacarpal dislocation complicated by dislocation of the os trapesium is reported in this paper. The patient's wrist healed with good functional results, despite a partial mistake in diagnosis. The authors draw attention to the fact, that X-ray films taken at admission must be analysed carefully and intraoperative X-rays films must be taken. By demonstration their own mistake in diagnosis and treatment, the authors hope that a similar mistake will be avoided. Following early open or closed reduction, a temporary wire fixation of the metacarpal bones to the carpal bones is recommended in order to prevent redislocation."}
{"id": "PMID:24153", "title": "[Bullet embolism of the median cerebral artery].", "content": "A shot injury to the middle cerebral artery caused occlusion to the vessel by thrombosis and emboly of the missile. The projectil had been removed, but a thrombus formed in the a. cerebri media as a postoperative complication or by progression of a thrombosis in the internal carotid artery and after 19 days the patient died. A focal emollition of the left cerebral hemisphere was found at autopsy.", "contents": "[Bullet embolism of the median cerebral artery]. A shot injury to the middle cerebral artery caused occlusion to the vessel by thrombosis and emboly of the missile. The projectil had been removed, but a thrombus formed in the a. cerebri media as a postoperative complication or by progression of a thrombosis in the internal carotid artery and after 19 days the patient died. A focal emollition of the left cerebral hemisphere was found at autopsy."}
{"id": "PMID:24155", "title": "H2-receptor antagonists in perspective.", "content": "Cimetidine, like its predecessors burinamide and metiamide, has been shown in vitro to be a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in animals and man after both intravenous and oral administration. Doses sufficient to inhibit gastric secretions are without measureable effects on other physiologic systems. The main indication for cimetidine is in the treatment of duodenal ulcer and of the Zollinger-Ellison syndrome. Useful indications are treatment of gastric ulcer and pnacreatic insufficiency. Possible indications are prevention of gastrointestinal bleeding and treatment of peptic esophagitis. The neutrophil toxicity seen with metiamide has so far not been demonstrated with cimetidine; side effects with cimetidine have generally been trivial. In the future, H2-receptor antagonists are likely to become key therapeutic agents in diseases in which gastric acid-pepsin secretion plays a pathogenetic role.", "contents": "H2-receptor antagonists in perspective. Cimetidine, like its predecessors burinamide and metiamide, has been shown in vitro to be a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in animals and man after both intravenous and oral administration. Doses sufficient to inhibit gastric secretions are without measureable effects on other physiologic systems. The main indication for cimetidine is in the treatment of duodenal ulcer and of the Zollinger-Ellison syndrome. Useful indications are treatment of gastric ulcer and pnacreatic insufficiency. Possible indications are prevention of gastrointestinal bleeding and treatment of peptic esophagitis. The neutrophil toxicity seen with metiamide has so far not been demonstrated with cimetidine; side effects with cimetidine have generally been trivial. In the future, H2-receptor antagonists are likely to become key therapeutic agents in diseases in which gastric acid-pepsin secretion plays a pathogenetic role."}
{"id": "PMID:24156", "title": "Neural and endocrine development after chronic tryptophan deficiency in rats: I. Brain monoamine and pituitary responses.", "content": "Caloric restriction and tryptophan deficient diets have been shown to delay aging in the immature laboratory rat. Studies of monoamine levels in the brain of developing female rats fed on these diets show changes in serotonin but not norepinephrine or dopamine levels: in tryptophan-restricted rats serotonin levels were reduced in all brain areas studied, whereas in caloric-restricted animals serotonin levels were increased in the cerebral hemispheres only. Another group of animals, in which growth and maturation was delayed by feeding d,1-parachlorophenylalanine (PCPA) showed decreases in serotonin, norepinephrine and dopamine concentrations in all brain regions investigated. All treatments employed to arrest growth and maturation resulted in pituitary alterations manifested by gross, histological and ultrastructural changes. It is postulated that there maturation- and age-retarding treatments delay the development of the central nervous system resulting in postponed maturation of the neuroendocrine axis, with consequent hypoactivity of certain pituitary functions and a resultant delay in the onset of maturation and senescence.", "contents": "Neural and endocrine development after chronic tryptophan deficiency in rats: I. Brain monoamine and pituitary responses. Caloric restriction and tryptophan deficient diets have been shown to delay aging in the immature laboratory rat. Studies of monoamine levels in the brain of developing female rats fed on these diets show changes in serotonin but not norepinephrine or dopamine levels: in tryptophan-restricted rats serotonin levels were reduced in all brain areas studied, whereas in caloric-restricted animals serotonin levels were increased in the cerebral hemispheres only. Another group of animals, in which growth and maturation was delayed by feeding d,1-parachlorophenylalanine (PCPA) showed decreases in serotonin, norepinephrine and dopamine concentrations in all brain regions investigated. All treatments employed to arrest growth and maturation resulted in pituitary alterations manifested by gross, histological and ultrastructural changes. It is postulated that there maturation- and age-retarding treatments delay the development of the central nervous system resulting in postponed maturation of the neuroendocrine axis, with consequent hypoactivity of certain pituitary functions and a resultant delay in the onset of maturation and senescence."}
{"id": "PMID:24161", "title": "Reactions between peroxidizing lipids and histidyl residue analogues: enhancement of lipid oxidation and browning by 4-methylimidazole.", "content": "As a part of our study on the interactions between peroxidizing lipids and the histidyl imidazole side-chain in simple, low-moisture model systems, 4-methylimidazole (4MI) was reacted with methyl linoleate (ML). This analogue was chosen to avoid interference from other functional groups in histidine (free base) or in proteins. Changes in the concentrations of lipid hydroperoxides, carbonyls, 4MI, and brown pigments were followed over a period of 24 days. The results indicate that 4MI exhibits significant prooxidative activity by reducing the induction period as well as by enhancing the formation of brown pigments. These effects are more pronounced at high 4MI/MI molar ratios and under basic pH's. Upon interactions with peroxidizing ML, as much as 44% of initially present 4MI was destroyed by the sixth day of incubation.", "contents": "Reactions between peroxidizing lipids and histidyl residue analogues: enhancement of lipid oxidation and browning by 4-methylimidazole. As a part of our study on the interactions between peroxidizing lipids and the histidyl imidazole side-chain in simple, low-moisture model systems, 4-methylimidazole (4MI) was reacted with methyl linoleate (ML). This analogue was chosen to avoid interference from other functional groups in histidine (free base) or in proteins. Changes in the concentrations of lipid hydroperoxides, carbonyls, 4MI, and brown pigments were followed over a period of 24 days. The results indicate that 4MI exhibits significant prooxidative activity by reducing the induction period as well as by enhancing the formation of brown pigments. These effects are more pronounced at high 4MI/MI molar ratios and under basic pH's. Upon interactions with peroxidizing ML, as much as 44% of initially present 4MI was destroyed by the sixth day of incubation."}
{"id": "PMID:24162", "title": "Patterns of the use of benzodiazepines in Australia.", "content": "In six suburban areas of Sydney, chosen to provide a socioeconomic cross-section of the city, complete records of dispensing of benzodiazepine were collected over a four-week period. These drugs constituted 3.7% of all dispensing, female patients outnumbered males by 2.3:1, and 98% of patients were over 20 years of age. The predominance of females, and higher age groups was found in all the areas studied, but no socioeconomic correlation was detected in the use of the drugs. Analysis of national dispensing figures confirmed the higher consumption in higher age groups, and revealed no heterogeneity in per capita prescribing rates amongst the States.", "contents": "Patterns of the use of benzodiazepines in Australia. In six suburban areas of Sydney, chosen to provide a socioeconomic cross-section of the city, complete records of dispensing of benzodiazepine were collected over a four-week period. These drugs constituted 3.7% of all dispensing, female patients outnumbered males by 2.3:1, and 98% of patients were over 20 years of age. The predominance of females, and higher age groups was found in all the areas studied, but no socioeconomic correlation was detected in the use of the drugs. Analysis of national dispensing figures confirmed the higher consumption in higher age groups, and revealed no heterogeneity in per capita prescribing rates amongst the States."}
{"id": "PMID:24163", "title": "The prevention of prematurity.", "content": "The prevention of prematurity requires identification of the patients most likely to go into labour prematurely and early recognition of threatened premature labour. There are unfortunately few clinical signs to help identify these patients, but certain features in the history are helpful. As soon as premature labour is diagnosed, energetic and active treatment with corticosteroids to advance pulmonary maturity and uterine suppression should be instituted. It is important to bear in mind that these patients should be managed in units, where not only is such treatment feasible, but neonatal intensive care is available, if labour cannot be suppressed.", "contents": "The prevention of prematurity. The prevention of prematurity requires identification of the patients most likely to go into labour prematurely and early recognition of threatened premature labour. There are unfortunately few clinical signs to help identify these patients, but certain features in the history are helpful. As soon as premature labour is diagnosed, energetic and active treatment with corticosteroids to advance pulmonary maturity and uterine suppression should be instituted. It is important to bear in mind that these patients should be managed in units, where not only is such treatment feasible, but neonatal intensive care is available, if labour cannot be suppressed."}
{"id": "PMID:24171", "title": "Kinetic studies on 3-hydroxykynureninase from rat liver.", "content": "3-Hydroxykynureninase was purified from rat liver. The Michaelis constants for L-kynurenine and L-3-hydroxykynurenine were determined to be 2.33 X 10(-4)M and 6.85 X 10(-5)M, respectively, at pH 8.41 and 37 degrees. With L-kynurenine as substrate, the enzyme was competitively inhibited by L-alanine, 3-hydroxyanthranilic acid, and several other compounds which contained structural features of either amino acid or aryl portions of the substrate. The effect of pH on the initial velocity, maximal velocity, and Michaelis constant, using L-kynurenine as substrate, was studied. Maximal velocity was strongly pH-dependent, with a maximum at pH 8.4. The Michaelis constant decreased from 11.4 X 10(-4)M at pH 7.1 to 1.30 X 10(-4)M at pH 9.0. Logarithmic plots of these data showed pKa's for functional groups ionizing in the enzyme-substrate complex and free enzyme active center of 7.6 and 8.5, respectively. Possible groups responsible for these ionizations were discussed.", "contents": "Kinetic studies on 3-hydroxykynureninase from rat liver. 3-Hydroxykynureninase was purified from rat liver. The Michaelis constants for L-kynurenine and L-3-hydroxykynurenine were determined to be 2.33 X 10(-4)M and 6.85 X 10(-5)M, respectively, at pH 8.41 and 37 degrees. With L-kynurenine as substrate, the enzyme was competitively inhibited by L-alanine, 3-hydroxyanthranilic acid, and several other compounds which contained structural features of either amino acid or aryl portions of the substrate. The effect of pH on the initial velocity, maximal velocity, and Michaelis constant, using L-kynurenine as substrate, was studied. Maximal velocity was strongly pH-dependent, with a maximum at pH 8.4. The Michaelis constant decreased from 11.4 X 10(-4)M at pH 7.1 to 1.30 X 10(-4)M at pH 9.0. Logarithmic plots of these data showed pKa's for functional groups ionizing in the enzyme-substrate complex and free enzyme active center of 7.6 and 8.5, respectively. Possible groups responsible for these ionizations were discussed."}
{"id": "PMID:24179", "title": "Structural evidence for gene duplication in the evolution of the acid proteases.", "content": "X-ray studies of acid proteases indicate a bilobal structure with a well defined active site cleft. An intramolecular twofold symmetry axis relates two topologically similar domains and the active site residues. A possible mechanism for evolution by gene duplication, divergence and gene fusion is presented.", "contents": "Structural evidence for gene duplication in the evolution of the acid proteases. X-ray studies of acid proteases indicate a bilobal structure with a well defined active site cleft. An intramolecular twofold symmetry axis relates two topologically similar domains and the active site residues. A possible mechanism for evolution by gene duplication, divergence and gene fusion is presented."}
{"id": "PMID:24188", "title": "Disequilibrium pH and bicarbonate reabsorption: relevance to the pathogenesis of distal renal tubular acidosis.", "content": "An augmented renal capacity to reabsorb bicarbonate (RHCO3) has been noted in patients with distal renal tubular acidosis (dRTA), and construed as evidence that the basic defect in dRTA is abnormal distal tubular permeability. According to this interpretation, the absence of a disequilibrium pH due to a back-leak of H2C03 permits increased distal H+ secretion and results in an increased RHCO3. To test this assumption, we have evaluated the effect of acute elimination of the disequilibrium pH by carbonic anhydrase infusion. The results establish that this maneuver doses not cause a rise in RHCO3. Thus, the elevated value of RHC3 described in dRTA cannot be the consequence of increased back-diffusion of H2CO3 and is more likely due to coexisting extracellular volume depletion and/or postassium deficiency.", "contents": "Disequilibrium pH and bicarbonate reabsorption: relevance to the pathogenesis of distal renal tubular acidosis. An augmented renal capacity to reabsorb bicarbonate (RHCO3) has been noted in patients with distal renal tubular acidosis (dRTA), and construed as evidence that the basic defect in dRTA is abnormal distal tubular permeability. According to this interpretation, the absence of a disequilibrium pH due to a back-leak of H2C03 permits increased distal H+ secretion and results in an increased RHCO3. To test this assumption, we have evaluated the effect of acute elimination of the disequilibrium pH by carbonic anhydrase infusion. The results establish that this maneuver doses not cause a rise in RHCO3. Thus, the elevated value of RHC3 described in dRTA cannot be the consequence of increased back-diffusion of H2CO3 and is more likely due to coexisting extracellular volume depletion and/or postassium deficiency."}
{"id": "PMID:24189", "title": "[Hemodynamic and electrocardiographic effects caused by intravenous infusion of a tricyclic antidepressive agent dibenzepin].", "content": "The cardiovascular (blood pressure, heart rate, central venous pressure) and ECG changes caused by dibenzepine-infusion (720 mg/day for 48 hours) have been assessed. Mean blood pressure and heart rate did not show significant changes. In some patients, however, distinct changes in both variables were observed. Central venous pressure was not affected. The infusion elicited changes in the repolarisation phase of the ECG: it did not, however, alter either the automaticity or the conductivity of the heart. These results were obtained in 40 depressive patients, whose general conditions and cardiovascular state were excellent and must not be extrapolated for cardiopathic patients. The risks inherent in this therapeutic approach are discussed.", "contents": "[Hemodynamic and electrocardiographic effects caused by intravenous infusion of a tricyclic antidepressive agent dibenzepin]. The cardiovascular (blood pressure, heart rate, central venous pressure) and ECG changes caused by dibenzepine-infusion (720 mg/day for 48 hours) have been assessed. Mean blood pressure and heart rate did not show significant changes. In some patients, however, distinct changes in both variables were observed. Central venous pressure was not affected. The infusion elicited changes in the repolarisation phase of the ECG: it did not, however, alter either the automaticity or the conductivity of the heart. These results were obtained in 40 depressive patients, whose general conditions and cardiovascular state were excellent and must not be extrapolated for cardiopathic patients. The risks inherent in this therapeutic approach are discussed."}
{"id": "PMID:24190", "title": "[Metabolic alkalosis. III. Spontaneous and experimental compensation mechanisms in plasma and erythrocytes].", "content": "Plasma and red cell acid-base balance were studied in 13 patients with metabolic alkalosis and 14 healthy subjects following the infusion of bicarbonate. Differences between the plasma and red cell patterns suggested that application of the results of plasma determinations to the body as a whole could be the cause of serious inaccuracies. Since the changes noted occurred in different combinations according to whether alkalinisation was acute or not, it is felt that cell response to a fall in (H+) varies in relation to the time available for compensation.", "contents": "[Metabolic alkalosis. III. Spontaneous and experimental compensation mechanisms in plasma and erythrocytes]. Plasma and red cell acid-base balance were studied in 13 patients with metabolic alkalosis and 14 healthy subjects following the infusion of bicarbonate. Differences between the plasma and red cell patterns suggested that application of the results of plasma determinations to the body as a whole could be the cause of serious inaccuracies. Since the changes noted occurred in different combinations according to whether alkalinisation was acute or not, it is felt that cell response to a fall in (H+) varies in relation to the time available for compensation."}
{"id": "PMID:24192", "title": "The use of relaxation and desensitisation techniques in eliminating a sleep problem.", "content": "This study describes the treatment of a 16-year-old youth unable to sleep, failing to respond to sleeping pills, who on a programme of relaxation and desensitisation in six weeks was able to control his sleeping patterns. On followup four months, six months and twelve months later this ability had been maintained.", "contents": "The use of relaxation and desensitisation techniques in eliminating a sleep problem. This study describes the treatment of a 16-year-old youth unable to sleep, failing to respond to sleeping pills, who on a programme of relaxation and desensitisation in six weeks was able to control his sleeping patterns. On followup four months, six months and twelve months later this ability had been maintained."}
{"id": "PMID:24193", "title": "Prazosin in hypertension. Part I. Clinical experience in 100 patients.", "content": "This paper reports the findings of an open evaluation of 100 patients treated with prazosin. When prazosin was added to existing hypotensive regimens in 50 patients whose blood pressure was poorly controlled, 36 (72 percent) became normotensive. Treatment was initiated with prazosin in a further 50 patients. Satisfactory control was achieved with prazosin alone in 24 and 20 of these became normotensive. The remaining 26 patients received in addition a beta-adrenoreceptor blocking agent together with a thiazide diuretic in 14. While prazosin alone caused a mean fall of 26/14mmHg in this group, the enchanced efficacy of combined therapy achieved a normal blood pressure in 19 (73 percent) and a total mean fall in pressure of 42/28mmHg. The most frequent side effect was dizziness or faintness at the start of therapy or, less often, when the dose was increased. This is minimised by using a low initial dose of 0.5mg two or three times daily. Prazosin is an effective hypotensive agent, used alone or in combination, in most patients with hypertension of all degrees of severity.", "contents": "Prazosin in hypertension. Part I. Clinical experience in 100 patients. This paper reports the findings of an open evaluation of 100 patients treated with prazosin. When prazosin was added to existing hypotensive regimens in 50 patients whose blood pressure was poorly controlled, 36 (72 percent) became normotensive. Treatment was initiated with prazosin in a further 50 patients. Satisfactory control was achieved with prazosin alone in 24 and 20 of these became normotensive. The remaining 26 patients received in addition a beta-adrenoreceptor blocking agent together with a thiazide diuretic in 14. While prazosin alone caused a mean fall of 26/14mmHg in this group, the enchanced efficacy of combined therapy achieved a normal blood pressure in 19 (73 percent) and a total mean fall in pressure of 42/28mmHg. The most frequent side effect was dizziness or faintness at the start of therapy or, less often, when the dose was increased. This is minimised by using a low initial dose of 0.5mg two or three times daily. Prazosin is an effective hypotensive agent, used alone or in combination, in most patients with hypertension of all degrees of severity."}
{"id": "PMID:24194", "title": "Effects of lorazepam on hyperactivity in ratarded children.", "content": "Seven mentally-retarded children, diagnosed as hyperactive, participated in a double-blind trial of the drug lorazepam (Ativan). Statistical analysis of the behavioural records showed that hyperactivity was typically greater during lorazepam than during placebo periods. The degree of hyperactivity was not systematically related to dosage level. The drug is therefore contraindicated for the control of hyperactivity in mentally retarded children.", "contents": "Effects of lorazepam on hyperactivity in ratarded children. Seven mentally-retarded children, diagnosed as hyperactive, participated in a double-blind trial of the drug lorazepam (Ativan). Statistical analysis of the behavioural records showed that hyperactivity was typically greater during lorazepam than during placebo periods. The degree of hyperactivity was not systematically related to dosage level. The drug is therefore contraindicated for the control of hyperactivity in mentally retarded children."}
{"id": "PMID:24195", "title": "Initiation of human parturition. IX. Progesterone metabolism by placentas of early and late human gestation.", "content": "In in vitro studies it was found that, in the presence of added NADPH, the human placenta metabolizes progesterone to 20alpha-hydroxy-4-pregnen-3-one at increasing rates as pregnancy advances. A fivefold increase in 20alpha-hydroxysteroid oxidoreductase activity is observed in term placentas compared with the enzymic activity of placentas of 12 to 20 weeks' gestation (368 +/- 53 pmoles/mg protein/hr vs 71 +/- 8 pmoles/mg protein/hr). The 5alpha-reductase and 3beta-hydroxysteroid oxidoreductase activities were similar in placentas obtained from early and late human pregnancies.", "contents": "Initiation of human parturition. IX. Progesterone metabolism by placentas of early and late human gestation. In in vitro studies it was found that, in the presence of added NADPH, the human placenta metabolizes progesterone to 20alpha-hydroxy-4-pregnen-3-one at increasing rates as pregnancy advances. A fivefold increase in 20alpha-hydroxysteroid oxidoreductase activity is observed in term placentas compared with the enzymic activity of placentas of 12 to 20 weeks' gestation (368 +/- 53 pmoles/mg protein/hr vs 71 +/- 8 pmoles/mg protein/hr). The 5alpha-reductase and 3beta-hydroxysteroid oxidoreductase activities were similar in placentas obtained from early and late human pregnancies."}
{"id": "PMID:24196", "title": "[Development of hematopietic and lymphoid tissues in conjoint bone marrow and thymus transplants].", "content": "The model of heterotopic transplantation of the mixture of bone marrow and thymus fragments was used to study the interaction of hemopoietic and lymphoid tissues under their direct contact. The bone marrow and thymus fragments of adult mice F1 (CBAXXC57BL) were transplanted separately or in the mixture under the kidney capsule of mice of the same strain. During the whole period of observation (from 10 days up to 14 months), the development of bone marrow and thymus fragments in the joint transplants proceeded independently, no \"mixed\" stroma appeared, and the stroma of each organ ensured the differentiation characteristic of its organ. The development of joint transplants somewhat differs from that of isolated transplants: on the 10th day a greater amount of hemopoietic tissues was noted in the former; the bone marrow component increases continuously up to 6 months (vs. 1--2 months in the isolated transplants); the bone and hemopoietic tissues predominate in the joint transplants by 14 months, the amount of thymic tissue markedly decreases but it does not disappear completely.", "contents": "[Development of hematopietic and lymphoid tissues in conjoint bone marrow and thymus transplants]. The model of heterotopic transplantation of the mixture of bone marrow and thymus fragments was used to study the interaction of hemopoietic and lymphoid tissues under their direct contact. The bone marrow and thymus fragments of adult mice F1 (CBAXXC57BL) were transplanted separately or in the mixture under the kidney capsule of mice of the same strain. During the whole period of observation (from 10 days up to 14 months), the development of bone marrow and thymus fragments in the joint transplants proceeded independently, no \"mixed\" stroma appeared, and the stroma of each organ ensured the differentiation characteristic of its organ. The development of joint transplants somewhat differs from that of isolated transplants: on the 10th day a greater amount of hemopoietic tissues was noted in the former; the bone marrow component increases continuously up to 6 months (vs. 1--2 months in the isolated transplants); the bone and hemopoietic tissues predominate in the joint transplants by 14 months, the amount of thymic tissue markedly decreases but it does not disappear completely."}
{"id": "PMID:24201", "title": "Stimulation of the activity of Schistosoma mansoni miracidia by snail-conditioned water.", "content": "A dark-ground photographic technique was used to analyse the reactions of Schistosoma mansoni miracidia to homogeneous solutions of snail-conditioned water (SCW). The most significant effect of this water was to increase miracidial turning. This effect was maintained under both acid and alkaline conditions, after passage of the SCW through a mixed bed resin and after chelation of either calcium or both calcium and magnesium ions. The stimulant in the water was unaffected by trypsin but was protease-sensitive, suggesting its possible identity as a peptide. The importance of 'active spaces' rather than concentration gradients in miracidial host-location was emphasized.", "contents": "Stimulation of the activity of Schistosoma mansoni miracidia by snail-conditioned water. A dark-ground photographic technique was used to analyse the reactions of Schistosoma mansoni miracidia to homogeneous solutions of snail-conditioned water (SCW). The most significant effect of this water was to increase miracidial turning. This effect was maintained under both acid and alkaline conditions, after passage of the SCW through a mixed bed resin and after chelation of either calcium or both calcium and magnesium ions. The stimulant in the water was unaffected by trypsin but was protease-sensitive, suggesting its possible identity as a peptide. The importance of 'active spaces' rather than concentration gradients in miracidial host-location was emphasized."}
{"id": "PMID:24208", "title": "Poisoning in children under age 5: identification and treatment.", "content": "A rational approach to management of poisoning in young children requires assessment of what, when, and how much drug was ingested. Emesis, if indicated, is followed by general supportive measures, enhanced removal of absorbed poison, and antidote therapy.", "contents": "Poisoning in children under age 5: identification and treatment. A rational approach to management of poisoning in young children requires assessment of what, when, and how much drug was ingested. Emesis, if indicated, is followed by general supportive measures, enhanced removal of absorbed poison, and antidote therapy."}
{"id": "PMID:24209", "title": "The biochemistry of the basal ganglia and Parkinson's disease.", "content": "The metabolic pathways for five transmitters in the basal ganglia are briefly described; the results of determinations of their concentrations, of their rate-limiting enzymes and of their degradation products are summarized. The changes found in Parkinson's disease are described. While dopamine synthesis in the basal ganglia is defective in this condition, abnormalities of other transmitters occur, and their possible significance is discussed.", "contents": "The biochemistry of the basal ganglia and Parkinson's disease. The metabolic pathways for five transmitters in the basal ganglia are briefly described; the results of determinations of their concentrations, of their rate-limiting enzymes and of their degradation products are summarized. The changes found in Parkinson's disease are described. While dopamine synthesis in the basal ganglia is defective in this condition, abnormalities of other transmitters occur, and their possible significance is discussed."}
{"id": "PMID:24210", "title": "Urticaria--current concepts.", "content": "The mechanisms, clinical features and management of the various forms of urticaria are discussed. The importance of histamine receptors, complement and the kinin cascade are reviewed.", "contents": "Urticaria--current concepts. The mechanisms, clinical features and management of the various forms of urticaria are discussed. The importance of histamine receptors, complement and the kinin cascade are reviewed."}
{"id": "PMID:24212", "title": "Evidence for acceleration of the rate of elongation of tyrosine aminotransferase nascent chains by dibutyryl cyclic AMP.", "content": "Analogs of cyclic AMP elevate the synthesis of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase; EC 2.6.1.5) in cultured hepatoma cells and rat liver at a post-transcriptional level but have no discernible effect on total soluble protein synthesis. In order to determine whether cyclic AMP exerts its effect on a step before or after initiation of the synthesis of this enzyme, we have analyzed the ribosomal transit times for both the aminotransferase and total soluble protein in hepatoma cells incubated in the presence or absence of N(6),O(2)'-dibutyryl cyclic AMP. The time required for one ribosome to translate one subunit of the \"average\" soluble protein (transit time) was about 2 min in cells incubated with or without the cyclic AMP analog. In contrast, the transit time for tyrosine aminotransferase was found to be reduced from 5-8 min under basal conditions to as low as 45 sec after exposure to dibutyryl cyclic AMP. Although the degree of effect varied from experiment to experiment, the relative rate of aminotransferase nascent chain elongation was found to be proportional to the stimulation of its activity. In contrast, dexamethasone did not alter the rate of aminotransferase elongation even though it elevated enzyme activity between 5- and 10-fold. These data are consistent with the hypothesis that induction of tyrosine aminotransferase with cyclic AMP analogs occurs by stimulation of the rate at which ribosomes translate pre-existing mRNA in contrast to adrenal steroids which act by increasing the level of translatable mRNA coding for this enzyme.", "contents": "Evidence for acceleration of the rate of elongation of tyrosine aminotransferase nascent chains by dibutyryl cyclic AMP. Analogs of cyclic AMP elevate the synthesis of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase; EC 2.6.1.5) in cultured hepatoma cells and rat liver at a post-transcriptional level but have no discernible effect on total soluble protein synthesis. In order to determine whether cyclic AMP exerts its effect on a step before or after initiation of the synthesis of this enzyme, we have analyzed the ribosomal transit times for both the aminotransferase and total soluble protein in hepatoma cells incubated in the presence or absence of N(6),O(2)'-dibutyryl cyclic AMP. The time required for one ribosome to translate one subunit of the \"average\" soluble protein (transit time) was about 2 min in cells incubated with or without the cyclic AMP analog. In contrast, the transit time for tyrosine aminotransferase was found to be reduced from 5-8 min under basal conditions to as low as 45 sec after exposure to dibutyryl cyclic AMP. Although the degree of effect varied from experiment to experiment, the relative rate of aminotransferase nascent chain elongation was found to be proportional to the stimulation of its activity. In contrast, dexamethasone did not alter the rate of aminotransferase elongation even though it elevated enzyme activity between 5- and 10-fold. These data are consistent with the hypothesis that induction of tyrosine aminotransferase with cyclic AMP analogs occurs by stimulation of the rate at which ribosomes translate pre-existing mRNA in contrast to adrenal steroids which act by increasing the level of translatable mRNA coding for this enzyme."}
{"id": "PMID:24213", "title": "Agonist-induced increase in apparent beta-adrenergic receptor size.", "content": "The properties of digitonin-solubilized beta-adrenergic receptors from frog erythrocyte membranes were studied by gel exclusion chromatography on AcA 34 Ultragel. beta-Adrenergic receptor binding activity in these membranes can be identified by both an agonist ligand, [(3)H]hydroxybenzylisoproterenol, and the antagonist ligands, [(3)H]dihydroalprenolol and (125)I-labeled hydroxybenzylpindolol. Occupancy of the beta-adrenergic receptors with the [(3)H]hydroxybenzylisoproterenol agonist prior to their solubilization from the membrane leads to an increase in apparent receptor size. Alterations in the molecular size of the receptor cannot be mimicked by occupancy of the binding site with the antagonist ligands. Exposure of frog erythrocyte membranes to [(3)H]hydroxybenzylisoproterenol agonist in the presence of 10 muM Gpp(NH)(p), a guanyl nucleotide analog that exerts multiple regulatory effects on the catecholamine-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] system, results in the elution of the [(3)H]hydroxybenzylisoproterenol radioligand in both the region characteristic of the agonist-receptor complex and the region characteristic of the antagonist-receptor complex. The precise molecular interactions responsible for the agonist-induced increase in apparent beta-adrenergic receptor size are still unresolved. However, the low concentrations of agonist that are capable of altering apparent receptor size and the sensitivity of this effect to guanyl nucleotides suggest that these phenomena may be intimately involved in eliciting the physiological effects of beta-adrenergic catecholamines at the molecular level.", "contents": "Agonist-induced increase in apparent beta-adrenergic receptor size. The properties of digitonin-solubilized beta-adrenergic receptors from frog erythrocyte membranes were studied by gel exclusion chromatography on AcA 34 Ultragel. beta-Adrenergic receptor binding activity in these membranes can be identified by both an agonist ligand, [(3)H]hydroxybenzylisoproterenol, and the antagonist ligands, [(3)H]dihydroalprenolol and (125)I-labeled hydroxybenzylpindolol. Occupancy of the beta-adrenergic receptors with the [(3)H]hydroxybenzylisoproterenol agonist prior to their solubilization from the membrane leads to an increase in apparent receptor size. Alterations in the molecular size of the receptor cannot be mimicked by occupancy of the binding site with the antagonist ligands. Exposure of frog erythrocyte membranes to [(3)H]hydroxybenzylisoproterenol agonist in the presence of 10 muM Gpp(NH)(p), a guanyl nucleotide analog that exerts multiple regulatory effects on the catecholamine-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] system, results in the elution of the [(3)H]hydroxybenzylisoproterenol radioligand in both the region characteristic of the agonist-receptor complex and the region characteristic of the antagonist-receptor complex. The precise molecular interactions responsible for the agonist-induced increase in apparent beta-adrenergic receptor size are still unresolved. However, the low concentrations of agonist that are capable of altering apparent receptor size and the sensitivity of this effect to guanyl nucleotides suggest that these phenomena may be intimately involved in eliciting the physiological effects of beta-adrenergic catecholamines at the molecular level."}
{"id": "PMID:24214", "title": "Myristic acid stimulation of bacterial bioluminescence in \"aldehyde\" mutants.", "content": "The involvement of long chain aldehyde in bacterial luminescence was known both from its being required for light emission in the in vitro reaction with pure luciferase and from its ability to stimulate luminescence in vivo in a certain class of dark \"aldehyde\" mutants. We have found that the luminescence of some (but not all) of such aldehyde mutants is also stimulated by long chain aliphatic fatty acids, with a marked specificity for myristic (tetradecanoic) acid. This stimulation has been demonstrated in aldehyde mutants of two species of luminous bacteria, Beneckea harveyi and Photobacterium fischeri. The responses, both in intensity and yield, are proportional to the amount of added tetradecanoic acid over a 1000-fold range, down to 10 pmol ml-1. Unsaturated long chain fatty acids are potent inhibitors of the tetradecanoic acid stimulation, but they do not effect the in vivo luminescence of wild-type bacteria.", "contents": "Myristic acid stimulation of bacterial bioluminescence in \"aldehyde\" mutants. The involvement of long chain aldehyde in bacterial luminescence was known both from its being required for light emission in the in vitro reaction with pure luciferase and from its ability to stimulate luminescence in vivo in a certain class of dark \"aldehyde\" mutants. We have found that the luminescence of some (but not all) of such aldehyde mutants is also stimulated by long chain aliphatic fatty acids, with a marked specificity for myristic (tetradecanoic) acid. This stimulation has been demonstrated in aldehyde mutants of two species of luminous bacteria, Beneckea harveyi and Photobacterium fischeri. The responses, both in intensity and yield, are proportional to the amount of added tetradecanoic acid over a 1000-fold range, down to 10 pmol ml-1. Unsaturated long chain fatty acids are potent inhibitors of the tetradecanoic acid stimulation, but they do not effect the in vivo luminescence of wild-type bacteria."}
{"id": "PMID:24215", "title": "Self-association of hemoglobin betaSH chains is linked to oxygenation.", "content": "Self-association of unliganded beta(SH) chains into tetramers (4 beta(1) [unk] beta(4)) is experimentally found to be energetically less favorable (DeltaG(0) = -19.05 +/- 0.30 kcal) than the corresponding oligomerization of fully oxygenated chains (4 beta(1)X [unk] beta(4)X(4); DeltaG(0) = -22.45 +/- 0.35 kcal). Hence the tetramers must bind oxygen with a higher affinity than that of dissociated chains. Calculations are presented showing why this affinity difference is not easily detected. The linkage is in a direction opposite to that exhibited by normal hemoglobin A, in which oligomerization of high-affinity unliganded dimers (2 alphabeta [unk] alpha(2)beta(2)) leads to tetramers with decreased oxygen affinity. In contrast, the oligomerization of high-affinity, unliganded beta(SH) chains leads to tetramers with even higher affinity. The results imply the existence of at least two conformational states for beta chains. Effects of inositol hexaphosphate on beta chain association were investigated. Inositol hexaphosphate was found to have no measurable effect at pH 7.4, in contrast to pH 7 where very pronounced effects have been observed. Some theoretical aspects of the linkages are presented and the relationship of the findings to concepts of structural transition and allosteric regulation is discussed. In contrast to the beta chains, self-association of alpha chains into dimers was found to occur with the same free energy in both unliganded and fully oxygenated states. Thus, the self-association of alpha chains is not linked to oxygenation.", "contents": "Self-association of hemoglobin betaSH chains is linked to oxygenation. Self-association of unliganded beta(SH) chains into tetramers (4 beta(1) [unk] beta(4)) is experimentally found to be energetically less favorable (DeltaG(0) = -19.05 +/- 0.30 kcal) than the corresponding oligomerization of fully oxygenated chains (4 beta(1)X [unk] beta(4)X(4); DeltaG(0) = -22.45 +/- 0.35 kcal). Hence the tetramers must bind oxygen with a higher affinity than that of dissociated chains. Calculations are presented showing why this affinity difference is not easily detected. The linkage is in a direction opposite to that exhibited by normal hemoglobin A, in which oligomerization of high-affinity unliganded dimers (2 alphabeta [unk] alpha(2)beta(2)) leads to tetramers with decreased oxygen affinity. In contrast, the oligomerization of high-affinity, unliganded beta(SH) chains leads to tetramers with even higher affinity. The results imply the existence of at least two conformational states for beta chains. Effects of inositol hexaphosphate on beta chain association were investigated. Inositol hexaphosphate was found to have no measurable effect at pH 7.4, in contrast to pH 7 where very pronounced effects have been observed. Some theoretical aspects of the linkages are presented and the relationship of the findings to concepts of structural transition and allosteric regulation is discussed. In contrast to the beta chains, self-association of alpha chains into dimers was found to occur with the same free energy in both unliganded and fully oxygenated states. Thus, the self-association of alpha chains is not linked to oxygenation."}
{"id": "PMID:24216", "title": "Characterization of the residual adenosine deaminating activity in the spleen of a patient with combined immunodeficiency disease and adenosine deaminase deficiency.", "content": "A number of infants with an autosomal recessive form of combined immunodeficiency disease also lack adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) activity in their erythrocytes. Other tissues from these infants contain only a few percent of the adenosine-deaminating activity present in corresponding normal tissue. The residual adenosine-deaminating activity in extracts from the spleen of a combined immunodeficient, adenosine deaminase-deficient patient was compared with adenosine deaminase from normal spleen. Affinity and immunoadsorbant column chromatography revealed distinct differences between the adenosine-deaminating activity in the patient's spleen and adenosine deaminase from normal spleen. The point of maximum activity and general configuration of the pH optimum curves were also different. erythro-9-(2-Hydroxyl-3-nonyl)adenine, a potent inhibitor of adenosine deaminase from normal spleen, had relatively little effect on the activity from the patient's spleen. In contrast, adenine was a better inhibitor of the activity in the patient's spleen than it was of the enzyme from normal tissue. An adenosine-deaminating activity with the same characteristics and specific activity as that in the patient's spleen was also isolated from normal spleen. These results suggest that the adenosine-deaminating activity in the spleen of this patient is not due to a mutant form of adenosine deaminase.", "contents": "Characterization of the residual adenosine deaminating activity in the spleen of a patient with combined immunodeficiency disease and adenosine deaminase deficiency. A number of infants with an autosomal recessive form of combined immunodeficiency disease also lack adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) activity in their erythrocytes. Other tissues from these infants contain only a few percent of the adenosine-deaminating activity present in corresponding normal tissue. The residual adenosine-deaminating activity in extracts from the spleen of a combined immunodeficient, adenosine deaminase-deficient patient was compared with adenosine deaminase from normal spleen. Affinity and immunoadsorbant column chromatography revealed distinct differences between the adenosine-deaminating activity in the patient's spleen and adenosine deaminase from normal spleen. The point of maximum activity and general configuration of the pH optimum curves were also different. erythro-9-(2-Hydroxyl-3-nonyl)adenine, a potent inhibitor of adenosine deaminase from normal spleen, had relatively little effect on the activity from the patient's spleen. In contrast, adenine was a better inhibitor of the activity in the patient's spleen than it was of the enzyme from normal tissue. An adenosine-deaminating activity with the same characteristics and specific activity as that in the patient's spleen was also isolated from normal spleen. These results suggest that the adenosine-deaminating activity in the spleen of this patient is not due to a mutant form of adenosine deaminase."}
{"id": "PMID:24217", "title": "Proliferative capacity of murine hematopoietic stem cells.", "content": "The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferative quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cell progress in the continuum in one direction and such progression is not reversible.", "contents": "Proliferative capacity of murine hematopoietic stem cells. The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferative quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cell progress in the continuum in one direction and such progression is not reversible."}
{"id": "PMID:24218", "title": "Genetic dissection of short-term and long-term facilitation at the Drosophila neuromuscular junction.", "content": "Transmitter release at the Drosophila larval neuromuscular junction may be increased by previous activity of the nerve. This facilitation phenomenon involves at least two processes, one short-term and other long-term. These are shown to based on different mechanisms because (i) a mutant was found that had abnormal long-term facilitation but normal short-term  facilitation; and (ii) long-term facilitation was eliminated by tetrodotoxin or by removing external Na+ but short-term facilitation was not. In long-term facilitation, there was a prolonged release of transmitter due to a prolonged Ca2+ sensitivity of the presynaptic terminal after each nerve stimulus. The cause of this is probably accumulation of Na+ inside the nerve terminal.", "contents": "Genetic dissection of short-term and long-term facilitation at the Drosophila neuromuscular junction. Transmitter release at the Drosophila larval neuromuscular junction may be increased by previous activity of the nerve. This facilitation phenomenon involves at least two processes, one short-term and other long-term. These are shown to based on different mechanisms because (i) a mutant was found that had abnormal long-term facilitation but normal short-term  facilitation; and (ii) long-term facilitation was eliminated by tetrodotoxin or by removing external Na+ but short-term facilitation was not. In long-term facilitation, there was a prolonged release of transmitter due to a prolonged Ca2+ sensitivity of the presynaptic terminal after each nerve stimulus. The cause of this is probably accumulation of Na+ inside the nerve terminal."}
{"id": "PMID:24225", "title": "Effect of antipsychotic and other classes of drugs on spontaneous locomotor activity and neurotoxicity in mice.", "content": "Quantitative estimates were made of the effects of several classes of drugs on spontaneous activity and neurotoxicity in mice. Clinically effective antipsychotic agents had a more selective action on spontaneous activity than other classes of drugs with the exception of clonidine and a related compound.", "contents": "Effect of antipsychotic and other classes of drugs on spontaneous locomotor activity and neurotoxicity in mice. Quantitative estimates were made of the effects of several classes of drugs on spontaneous activity and neurotoxicity in mice. Clinically effective antipsychotic agents had a more selective action on spontaneous activity than other classes of drugs with the exception of clonidine and a related compound."}
{"id": "PMID:24234", "title": "Granulomatous ileocolitis (Crohn's disease).", "content": "In a clinical survey, the symptoms, associated diseases, and local and metabolic complications of Crohn's disease are discussed. Medical treatment (with SASP, corticosteroids, and immunosuppressives), as well as treatment for malnutrition, is of special importance.", "contents": "Granulomatous ileocolitis (Crohn's disease). In a clinical survey, the symptoms, associated diseases, and local and metabolic complications of Crohn's disease are discussed. Medical treatment (with SASP, corticosteroids, and immunosuppressives), as well as treatment for malnutrition, is of special importance."}
{"id": "PMID:24235", "title": "Prostaglandin synthesis in human placenta and fetal membranes.", "content": "The conversion of exogenous arachidonic acid into prostaglandins was studied in human placenta and fetal membrane microsomes. Only one prostaglandin was formed, prostaglandin E2 (PGE2), in fetal membrane microsomes. In placental microsomes PGE2 was further transformed into 15 keto-PGE2. Cofactor requirements and some characteristics of the system were studied. 1 to 3% conversion of arachidonic acid into prostaglandins was observed in placental microsomes and 5 to 8% conversion in fetal membrane microsomes.", "contents": "Prostaglandin synthesis in human placenta and fetal membranes. The conversion of exogenous arachidonic acid into prostaglandins was studied in human placenta and fetal membrane microsomes. Only one prostaglandin was formed, prostaglandin E2 (PGE2), in fetal membrane microsomes. In placental microsomes PGE2 was further transformed into 15 keto-PGE2. Cofactor requirements and some characteristics of the system were studied. 1 to 3% conversion of arachidonic acid into prostaglandins was observed in placental microsomes and 5 to 8% conversion in fetal membrane microsomes."}
{"id": "PMID:24241", "title": "Tissue and blood gamma-glutamyl transferase distribution in the pig.", "content": "Gamma-glutamyl transferase distribution was studied in 10 pigs with an average weight of 100 kg. It was shown that kidney had the highest concentration of the enzyme, followed by pancreas, spleen and liver. Blood activities measured in plasma and sera from 54 animals were very similar, ie, 35+/-21 iu/litre for plasma and 36+/-14 iu/litre for serum.", "contents": "Tissue and blood gamma-glutamyl transferase distribution in the pig. Gamma-glutamyl transferase distribution was studied in 10 pigs with an average weight of 100 kg. It was shown that kidney had the highest concentration of the enzyme, followed by pancreas, spleen and liver. Blood activities measured in plasma and sera from 54 animals were very similar, ie, 35+/-21 iu/litre for plasma and 36+/-14 iu/litre for serum."}
{"id": "PMID:24242", "title": "An investigation into the viability of broth cultures of the T1 strain of Mycoplasma mycoides sub-species mycoides.", "content": "The T1 broth vaccine against contagious bovine pleuropneumonia can only be stored for four weeks at +4 degrees C because after that time the titre of Mycoplasma mycoides sub-species mycoides falls below the minimal vaccinating dose. An investigation into the death of these organisms during the stationary growth phase was made. The culture medium in which the vaccine was prepared was found to contain adequate nutrients. Control of the pH by the addition of KOH was shown to preserve the viability of the organism: there was no drop in titre during 336 h (14 days) at 37 degrees C. Use of this technique may prove valuable as a means of preserving the viability of T1 broth vaccine.", "contents": "An investigation into the viability of broth cultures of the T1 strain of Mycoplasma mycoides sub-species mycoides. The T1 broth vaccine against contagious bovine pleuropneumonia can only be stored for four weeks at +4 degrees C because after that time the titre of Mycoplasma mycoides sub-species mycoides falls below the minimal vaccinating dose. An investigation into the death of these organisms during the stationary growth phase was made. The culture medium in which the vaccine was prepared was found to contain adequate nutrients. Control of the pH by the addition of KOH was shown to preserve the viability of the organism: there was no drop in titre during 336 h (14 days) at 37 degrees C. Use of this technique may prove valuable as a means of preserving the viability of T1 broth vaccine."}
{"id": "PMID:24243", "title": "Activities of ketone body utilising enzymes in tissues of fed and fasted sheep.", "content": "The activities of 3-hydroxybutyrate dehydrogenase, 3-ketoacid CoA-transferase and acetyl-CoA acetyltransferase have been measured in the kidney, heart and brain of fed and four-day fasted ewes. The results indicate tha there is a decrease in the capacity of these organs to catabolise ketone bodies in fasting ketosis.", "contents": "Activities of ketone body utilising enzymes in tissues of fed and fasted sheep. The activities of 3-hydroxybutyrate dehydrogenase, 3-ketoacid CoA-transferase and acetyl-CoA acetyltransferase have been measured in the kidney, heart and brain of fed and four-day fasted ewes. The results indicate tha there is a decrease in the capacity of these organs to catabolise ketone bodies in fasting ketosis."}
{"id": "PMID:24244", "title": "Clinical and metabolic consequences to cattle of rumen overdosing with di-ureido iso-butane (DUIB).", "content": "Di-ureido iso-butane (DUIB) was overdosed on three occasions to two year-old bullocks, under experimental conditions. Six g/kg live weight of DUIB was mixed manually into the rumen contents formed by a predominantly hay diet (10 kg) with added concentrates (2 kg). Marked clinical signs were observed for 72 h before recovery. Food and water intake were interrupted and a smell of ammonia saturated the accommodation. Blood concentrations of urea-nitrogen increased, while glucose fell; a metabolic alkalosis was present. Rumen VFA concentrations fell, but without altering the proportions of the individual acids present, pH increased, urea-nitrogen and ammonia-nitrogen concentrations fluctuated markedly. The pH of duodenal contents increased. Clinical recovery appeared complete after six days with biochemical homeostasis nearly restored.", "contents": "Clinical and metabolic consequences to cattle of rumen overdosing with di-ureido iso-butane (DUIB). Di-ureido iso-butane (DUIB) was overdosed on three occasions to two year-old bullocks, under experimental conditions. Six g/kg live weight of DUIB was mixed manually into the rumen contents formed by a predominantly hay diet (10 kg) with added concentrates (2 kg). Marked clinical signs were observed for 72 h before recovery. Food and water intake were interrupted and a smell of ammonia saturated the accommodation. Blood concentrations of urea-nitrogen increased, while glucose fell; a metabolic alkalosis was present. Rumen VFA concentrations fell, but without altering the proportions of the individual acids present, pH increased, urea-nitrogen and ammonia-nitrogen concentrations fluctuated markedly. The pH of duodenal contents increased. Clinical recovery appeared complete after six days with biochemical homeostasis nearly restored."}
{"id": "PMID:24261", "title": "A new method for determination of microsomal haem oxygenase (EC 1.14.99.3) based on quantitation of carbon monoxide formation.", "content": "Microsomal haem oxygenase (MHO) catalyses the main pathway for haem degradation. Hitherto bilirubin formation rate (BFR) has been used for determination of MHO activity. In the present study a method is described where MHO activity is assessed from the rate of carbon monoxide formation (VCO) in tissue homogenates with methaemalbumin as substrate. Formed CO is bound to haemoglobin present in the tissue homogenate. CO is measured by gas chromatography after reduction to methane. CO amounts of 0.01 nmol could be measured. This corresponded to an MHO activity of 0.05 pkat when using standard incubation mixture and 12 min incubation time. The correlation with MHO activity determined with the BFR technique was good (r = 0.94; n = 41); MHOVCO = 0.94-MHOBFR-0.08). Advantages with the VCO method are a ten-fold increase in sensitivity compared to the BFR method and independence of biliverdin reductase.", "contents": "A new method for determination of microsomal haem oxygenase (EC 1.14.99.3) based on quantitation of carbon monoxide formation. Microsomal haem oxygenase (MHO) catalyses the main pathway for haem degradation. Hitherto bilirubin formation rate (BFR) has been used for determination of MHO activity. In the present study a method is described where MHO activity is assessed from the rate of carbon monoxide formation (VCO) in tissue homogenates with methaemalbumin as substrate. Formed CO is bound to haemoglobin present in the tissue homogenate. CO is measured by gas chromatography after reduction to methane. CO amounts of 0.01 nmol could be measured. This corresponded to an MHO activity of 0.05 pkat when using standard incubation mixture and 12 min incubation time. The correlation with MHO activity determined with the BFR technique was good (r = 0.94; n = 41); MHOVCO = 0.94-MHOBFR-0.08). Advantages with the VCO method are a ten-fold increase in sensitivity compared to the BFR method and independence of biliverdin reductase."}
{"id": "PMID:24262", "title": "Dissolution and uptake of cadmium from dental gold solder alloy implants.", "content": "Pure metallic cadmium was irradiated by means of thermal neutrons. The irradiated cadmium (115Cd) was placed in bags of gold foil and the bags were implanted subcutaneously in the neck region of mice. Two and 3d respectively after implantation the mice were killed, the bags removed and the animals subjected to whole-body autoradiography. The autoradiograms revealed an uptake of 115Cd in liver and kidney. In another experiment specimens of a cadmium-containing dental gold solder alloy, a cadmium-free dental casting gold alloy and soldered assemblies made of these two alloys were implanted subcutaneously in the neck region of mice. The animals were killed after 6 months; cadmium analysis showed significant increases in the cadmium concentration in liver and kidney of those mice which had been given implants of gold solder alloy. The study clearly shows that due to electrochemical corrosion cadmium can be released from implants and accumulated in the kidneys and the liver.", "contents": "Dissolution and uptake of cadmium from dental gold solder alloy implants. Pure metallic cadmium was irradiated by means of thermal neutrons. The irradiated cadmium (115Cd) was placed in bags of gold foil and the bags were implanted subcutaneously in the neck region of mice. Two and 3d respectively after implantation the mice were killed, the bags removed and the animals subjected to whole-body autoradiography. The autoradiograms revealed an uptake of 115Cd in liver and kidney. In another experiment specimens of a cadmium-containing dental gold solder alloy, a cadmium-free dental casting gold alloy and soldered assemblies made of these two alloys were implanted subcutaneously in the neck region of mice. The animals were killed after 6 months; cadmium analysis showed significant increases in the cadmium concentration in liver and kidney of those mice which had been given implants of gold solder alloy. The study clearly shows that due to electrochemical corrosion cadmium can be released from implants and accumulated in the kidneys and the liver."}
{"id": "PMID:24263", "title": "Composition of the alkaline component of human gastric juice: effect of swallowed saliva and duodeno-gastric reflux.", "content": "Five patients (four with vitiligo and one with pernicious anaemia) were subjected to the histamine infusion test; there were achlorhydric while the remaining two secreted quite small amounts of acid. [Na+],[Cl-)and[alkali]were determined in the alkaline gastric juice samples (pH greater than 7.0). In order to assess the contribution of swallowed saliva the histamine test was done twice in each patient: (A) with precautions to prevent swallowing of saliva; and (B) with the patient allowed to swallow saliva freely. In each sample reflux of duodenal juice was estimated so that its contribution to the alkaline gastric aspirate could be assessed. Such reflex was absent in one patient, negligible in another, while in the remaining three patients the mean pyloric reflux amounted to no more than 8% of the observed volume. Swallowed saliva had diluting effect on [Na+] and [Cl-] but raised K+ concentration in the alkaline gastric aspirate. The comparison of alkaline gastric juice, free to an appreciable extent of salivary contamination, was shown to be relatively constant. The results are consistent with the two-component hypothesis of gastric secretion.", "contents": "Composition of the alkaline component of human gastric juice: effect of swallowed saliva and duodeno-gastric reflux. Five patients (four with vitiligo and one with pernicious anaemia) were subjected to the histamine infusion test; there were achlorhydric while the remaining two secreted quite small amounts of acid. [Na+],[Cl-)and[alkali]were determined in the alkaline gastric juice samples (pH greater than 7.0). In order to assess the contribution of swallowed saliva the histamine test was done twice in each patient: (A) with precautions to prevent swallowing of saliva; and (B) with the patient allowed to swallow saliva freely. In each sample reflux of duodenal juice was estimated so that its contribution to the alkaline gastric aspirate could be assessed. Such reflex was absent in one patient, negligible in another, while in the remaining three patients the mean pyloric reflux amounted to no more than 8% of the observed volume. Swallowed saliva had diluting effect on [Na+] and [Cl-] but raised K+ concentration in the alkaline gastric aspirate. The comparison of alkaline gastric juice, free to an appreciable extent of salivary contamination, was shown to be relatively constant. The results are consistent with the two-component hypothesis of gastric secretion."}
{"id": "PMID:24264", "title": "A sensitive method for specific quantitation of secretory IgA.", "content": "A method to quantitate specifically secretory IgA (SIgA) has been developed using the enzyme-linked immunosorbent assay. The IgA in the test sample was adsorbed to anti-alpha antibodies attached to plastic tubes via a cost of IgA myeloma protein. The reacted SIgA was determined using anti-secretory component antiserum conjugated with alkaline phosphatase. The technique permitted quantitation of secretory IgA in biological fluids like milk, urine, and saliva with a reproducibility of +/-7%, down to 0.03 mg/l. In contrast to earlier techniques, the presence of up to 157% of serum IgA without secretory component (SC) and free SC did not disturb the measurements of SIgA. Furthermore, variations in pH and osmolarity, within biological ranges in secretions, did not influence the estimations.", "contents": "A sensitive method for specific quantitation of secretory IgA. A method to quantitate specifically secretory IgA (SIgA) has been developed using the enzyme-linked immunosorbent assay. The IgA in the test sample was adsorbed to anti-alpha antibodies attached to plastic tubes via a cost of IgA myeloma protein. The reacted SIgA was determined using anti-secretory component antiserum conjugated with alkaline phosphatase. The technique permitted quantitation of secretory IgA in biological fluids like milk, urine, and saliva with a reproducibility of +/-7%, down to 0.03 mg/l. In contrast to earlier techniques, the presence of up to 157% of serum IgA without secretory component (SC) and free SC did not disturb the measurements of SIgA. Furthermore, variations in pH and osmolarity, within biological ranges in secretions, did not influence the estimations."}
{"id": "PMID:24265", "title": "Detection of hepatitis B antigen in circulating immune complexes in acute and chronic hepatitis.", "content": "By using polyethylene glycol precipitation at low concentration (PEG test) and the radiolabeled C1q binding test, immune complexes were detected sera from acute (23/28) and chronic (28/32) hepatitis patients, hemodialyzed patients with chronic hepatitis B surface (HBs) antigenemia (7/19), and asymptomatic HBs antigen carriers (2/11). After treatment of PEG precipitates with acidic pH, heating, or proteolytic enzyme (protease), electroimmunodiffusion or radioimmunoassay revealed the presence of HBs antigen or antibody in dissociated immune complexes in sera from several acute and chronic hepatitis patients. Electron microscopy showed immune complexes of HB virus in 9 of 12 PEG precipitates obtained from PEG-test-positive sera; these 9 precipitates were from patients with acute or chronic hepatitis and the other three from chronic HBs Ag carriers. Free HB virus particles were observed after protease digestion of PEG precipitates. Neither immune complexes nor virus particles were seen in precipitates from PEG-test-negative but HBs-Ag-positive sera from chronic carriers.", "contents": "Detection of hepatitis B antigen in circulating immune complexes in acute and chronic hepatitis. By using polyethylene glycol precipitation at low concentration (PEG test) and the radiolabeled C1q binding test, immune complexes were detected sera from acute (23/28) and chronic (28/32) hepatitis patients, hemodialyzed patients with chronic hepatitis B surface (HBs) antigenemia (7/19), and asymptomatic HBs antigen carriers (2/11). After treatment of PEG precipitates with acidic pH, heating, or proteolytic enzyme (protease), electroimmunodiffusion or radioimmunoassay revealed the presence of HBs antigen or antibody in dissociated immune complexes in sera from several acute and chronic hepatitis patients. Electron microscopy showed immune complexes of HB virus in 9 of 12 PEG precipitates obtained from PEG-test-positive sera; these 9 precipitates were from patients with acute or chronic hepatitis and the other three from chronic HBs Ag carriers. Free HB virus particles were observed after protease digestion of PEG precipitates. Neither immune complexes nor virus particles were seen in precipitates from PEG-test-negative but HBs-Ag-positive sera from chronic carriers."}
{"id": "PMID:24271", "title": "[Pipoxizin, a new bronchodilator].", "content": "Pipoxizin is a new bronchodilator with the chemical name chlorhydrate-4-diphenyl-methylene-1-(2-/2-(2-hydroxy-ethoxy)-ethoxy/-ethyl/-ethyl)-piperidine. This substance exhibits powerful antihistaminic and antiserotonin properties but no parasympathetic or beta-adrenergic properties. The effects of Pipoxizin have been compared with those of the wellknown product hexoprenalin (Ipradol). Twelve male patients, each with bronchial obstruction, took part in the trials. Plethysmography before and after Alupent inhalation was carried out to determine the reversibility or irreversibility of the bronchial obstruction. On the following day, the plethysmorgraphic tests were repeated before and after intravenous injection of Pipoxizin, and on the third day, the tests were repeated again after intravenous injection of hexoprenalin. Pulse and blood pressure were monitored. Following the use of Pipoxizin, there was a significant decrease in the following parameters: RT, RE, RV, ITGV, pulse rate, and systolic blood pressure. A significant increase was found in FEV1. After hexoprenalin injection, there was a significant decrease only in RV and an increase in FEV1. A comparison of Pipoxizin and hexoprenalin shows a significant difference between the two products, Pipoxizin having the more favourable effect.", "contents": "[Pipoxizin, a new bronchodilator]. Pipoxizin is a new bronchodilator with the chemical name chlorhydrate-4-diphenyl-methylene-1-(2-/2-(2-hydroxy-ethoxy)-ethoxy/-ethyl/-ethyl)-piperidine. This substance exhibits powerful antihistaminic and antiserotonin properties but no parasympathetic or beta-adrenergic properties. The effects of Pipoxizin have been compared with those of the wellknown product hexoprenalin (Ipradol). Twelve male patients, each with bronchial obstruction, took part in the trials. Plethysmography before and after Alupent inhalation was carried out to determine the reversibility or irreversibility of the bronchial obstruction. On the following day, the plethysmorgraphic tests were repeated before and after intravenous injection of Pipoxizin, and on the third day, the tests were repeated again after intravenous injection of hexoprenalin. Pulse and blood pressure were monitored. Following the use of Pipoxizin, there was a significant decrease in the following parameters: RT, RE, RV, ITGV, pulse rate, and systolic blood pressure. A significant increase was found in FEV1. After hexoprenalin injection, there was a significant decrease only in RV and an increase in FEV1. A comparison of Pipoxizin and hexoprenalin shows a significant difference between the two products, Pipoxizin having the more favourable effect."}
{"id": "PMID:24273", "title": "Nature and nurture in development of the autonomic neuron.", "content": "Arguments are presented for the hypothesis that during an early stage of development the cells which become principal neurons of the autonomic nervous system possess information regarding the positions they will occupy within the body. A second stage of development, during which a decision is made regarding which neurotransmitter to employ, is delayed until each neuron has assumed its permanent position in the body and has sampled, presumably via its growing axons, the peripheral field which it will innervate. The development of cholinergic mechanisms takes precedence; adrenergic neurons may develop only when cholinergic sites have been occupied. An extended period during which the differentiation of transmitter mechanisms may be modulated permits the neuron to adequately sample the periphery prior to commitment to a specific transmitter economy.", "contents": "Nature and nurture in development of the autonomic neuron. Arguments are presented for the hypothesis that during an early stage of development the cells which become principal neurons of the autonomic nervous system possess information regarding the positions they will occupy within the body. A second stage of development, during which a decision is made regarding which neurotransmitter to employ, is delayed until each neuron has assumed its permanent position in the body and has sampled, presumably via its growing axons, the peripheral field which it will innervate. The development of cholinergic mechanisms takes precedence; adrenergic neurons may develop only when cholinergic sites have been occupied. An extended period during which the differentiation of transmitter mechanisms may be modulated permits the neuron to adequately sample the periphery prior to commitment to a specific transmitter economy."}
{"id": "PMID:24275", "title": "Experimental Brugia timori and Wuchereria bancrofti infections in certain species of mosquitoes.", "content": "Laboratory reared Aedes aegypti (black eye and Jakarta strains), Aedes togoi, (Taiwan), Aedes albopictus, (Jakarta), wild caught Anopheles barbirostris, (Java) and Mansonia uniformis, (Jakarta) were fed on a carrier with mixed infection of Brugia timori and Wuchereria bancrofti. B. timori and W. bancrofti were able to develop in A. aegypti (black eye) and A. togoi, with development proceeding more rapidly for of B. timori than W. bancrofti. Both species of parasites were readily distinguishable in each of their developmental stages. A. barbirostris from Java was able to support development of B. timori as well as A. barbirostris from Flores. B. timori and W. bancrofti did not develop in M. uniformis, A. aegypti (Jakarta strain) and A. albopictus.", "contents": "Experimental Brugia timori and Wuchereria bancrofti infections in certain species of mosquitoes. Laboratory reared Aedes aegypti (black eye and Jakarta strains), Aedes togoi, (Taiwan), Aedes albopictus, (Jakarta), wild caught Anopheles barbirostris, (Java) and Mansonia uniformis, (Jakarta) were fed on a carrier with mixed infection of Brugia timori and Wuchereria bancrofti. B. timori and W. bancrofti were able to develop in A. aegypti (black eye) and A. togoi, with development proceeding more rapidly for of B. timori than W. bancrofti. Both species of parasites were readily distinguishable in each of their developmental stages. A. barbirostris from Java was able to support development of B. timori as well as A. barbirostris from Flores. B. timori and W. bancrofti did not develop in M. uniformis, A. aegypti (Jakarta strain) and A. albopictus."}
{"id": "PMID:24272", "title": "Genetic analysis of the nitrogen fixation system in Klebsiella pneumoniae.", "content": "Fine structure mapping of nif mutations of Klebsiella pneumoniae was accomplished by means of Pl-transductional crosses and the plasmid R144 drd mediated conjugations. The physical distance between nif mutations based on the percentage of co-transduction with hisD of the nif mutations was estimated. The maximal distance between two mutations was calculated about 3 Kb, and the average distance between different nif mutations was about 1 to 2 Kb. So no \"silent region\" was shown within the nif cluster nearby the histidine operon. Several hisD-unlinked nif mutants were isolated and investigated genetically and biochemically. They all differed from the glutamineless mutants, one of these mutants was tentatively assigned as a sort of N-assimilation mutant with little activity of glutamate synthetase. It differed from the known N-assimilation mutants in its absence of nitrogenase activity. Since the wild type hisD-linked nif genes carried by the plasmid RP4 failed to complement the defects of the hisD-unlinked nif genes in the recipient cells but they were effective to facilitate E. coli in acquiring the ability to fix nitrogen, which indicates that the hisD-unlinked nif genes necessary for the functioning of the hisD-linked nif genes are present in E. coli.", "contents": "Genetic analysis of the nitrogen fixation system in Klebsiella pneumoniae. Fine structure mapping of nif mutations of Klebsiella pneumoniae was accomplished by means of Pl-transductional crosses and the plasmid R144 drd mediated conjugations. The physical distance between nif mutations based on the percentage of co-transduction with hisD of the nif mutations was estimated. The maximal distance between two mutations was calculated about 3 Kb, and the average distance between different nif mutations was about 1 to 2 Kb. So no \"silent region\" was shown within the nif cluster nearby the histidine operon. Several hisD-unlinked nif mutants were isolated and investigated genetically and biochemically. They all differed from the glutamineless mutants, one of these mutants was tentatively assigned as a sort of N-assimilation mutant with little activity of glutamate synthetase. It differed from the known N-assimilation mutants in its absence of nitrogenase activity. Since the wild type hisD-linked nif genes carried by the plasmid RP4 failed to complement the defects of the hisD-unlinked nif genes in the recipient cells but they were effective to facilitate E. coli in acquiring the ability to fix nitrogen, which indicates that the hisD-unlinked nif genes necessary for the functioning of the hisD-linked nif genes are present in E. coli."}
{"id": "PMID:24280", "title": "Interactions of gastric blood flow, barrier breaker, and hydrogen ion back diffusion during ulcer formation in the rat.", "content": "A rat gastric chamber preparation was used to determine the interrelations between H+ back diffusion, mucosal blood flow, the area of mucosa treated with bile salts and ulcer formation. The rate of H+ back diffusion was found to be dependent on both mucosal blood flow and the area of mucosa exposed to bile salts. It is concluded that, although H+ back diffusion is a convenient measure of barrier permeability under conditions of normal mucosal blood flow, during mucosal ischemia this parameter fails to reflect permeability because of decreased mucosal clearance of H+. These findings would explain apparent controversy whereby ulceration occurs under shock conditions in the absence of apparent H+ back diffusion.", "contents": "Interactions of gastric blood flow, barrier breaker, and hydrogen ion back diffusion during ulcer formation in the rat. A rat gastric chamber preparation was used to determine the interrelations between H+ back diffusion, mucosal blood flow, the area of mucosa treated with bile salts and ulcer formation. The rate of H+ back diffusion was found to be dependent on both mucosal blood flow and the area of mucosa exposed to bile salts. It is concluded that, although H+ back diffusion is a convenient measure of barrier permeability under conditions of normal mucosal blood flow, during mucosal ischemia this parameter fails to reflect permeability because of decreased mucosal clearance of H+. These findings would explain apparent controversy whereby ulceration occurs under shock conditions in the absence of apparent H+ back diffusion."}
{"id": "PMID:24281", "title": "Lateral ventral (spigelian) hernias in infants and children.", "content": "Lateral ventral hernias are found in the spigelian fascia lateral to the junction of the arcuate and semilunar lines and below the level of the umbilicus. Three cases are reported in infants and children. Diagnosis depends on finding an unusual mass on the anterior abdominal wall and palpation of the rim of the hernia defect upon reduction of the mass. A spigelian hernia may be misdiagnosed easily if the examiner is unaware that it can occur in childhood. The edge of the defect must be outlined while the child is straining, prior to induction of anesthesia, as the rim may be difficult to find when the patient is asleep.", "contents": "Lateral ventral (spigelian) hernias in infants and children. Lateral ventral hernias are found in the spigelian fascia lateral to the junction of the arcuate and semilunar lines and below the level of the umbilicus. Three cases are reported in infants and children. Diagnosis depends on finding an unusual mass on the anterior abdominal wall and palpation of the rim of the hernia defect upon reduction of the mass. A spigelian hernia may be misdiagnosed easily if the examiner is unaware that it can occur in childhood. The edge of the defect must be outlined while the child is straining, prior to induction of anesthesia, as the rim may be difficult to find when the patient is asleep."}
{"id": "PMID:24284", "title": "The efficiency of diamphenethide in controlling natural infestations of Fasciola hepatica in lambs.", "content": "The activity of diamphenethide against natural infestations of Fasciola hepatica in fattening lambs was assessed on a farm with a noted history of fascioliasis. The main experimental groups, two treated and one control, grazed known contaminated pastures for a twelve week period after which they were removed to fluke-free areas to await slaughter. Three groups of four tracer lambs were each grazed for three successive four week periods with the main flock to determine continuity of infection. A single treatment with diamphenethide at 110 mg/kg bodyweight given when the sheep were removed from the trial area was 96.7% effective against the sub-chronic disease which had developed by this time. Three treatments at 110 mg diamphenethide/kg bodeweight given at intervals of four weeks during the grazing period proved to be 100% effective in preventing the establishment of the disease. Significant benefits in terms of weight gain were exhibited by the treated lambs.", "contents": "The efficiency of diamphenethide in controlling natural infestations of Fasciola hepatica in lambs. The activity of diamphenethide against natural infestations of Fasciola hepatica in fattening lambs was assessed on a farm with a noted history of fascioliasis. The main experimental groups, two treated and one control, grazed known contaminated pastures for a twelve week period after which they were removed to fluke-free areas to await slaughter. Three groups of four tracer lambs were each grazed for three successive four week periods with the main flock to determine continuity of infection. A single treatment with diamphenethide at 110 mg/kg bodyweight given when the sheep were removed from the trial area was 96.7% effective against the sub-chronic disease which had developed by this time. Three treatments at 110 mg diamphenethide/kg bodeweight given at intervals of four weeks during the grazing period proved to be 100% effective in preventing the establishment of the disease. Significant benefits in terms of weight gain were exhibited by the treated lambs."}
{"id": "PMID:24288", "title": "Arbovirus isolations from mosquitoes: Kano Plain, Kenya.", "content": "Arbovirus isolation attempts on 324,486 mosquitoes captured over a four-year period on the Kano Plain, Kenya, yielded 15 isolates including Pongola (six strains), Ilesha (three strains), Germiston (two strains), Sindbis (one strain), Barur (one strain) and two viruses which could not be characterized. Mansonia uniformis, Anopheles gambiae and Culex antennatus constituted 70% of the total collection and accounted for all of the isolates except one, which came from Anopheles funestus.", "contents": "Arbovirus isolations from mosquitoes: Kano Plain, Kenya. Arbovirus isolation attempts on 324,486 mosquitoes captured over a four-year period on the Kano Plain, Kenya, yielded 15 isolates including Pongola (six strains), Ilesha (three strains), Germiston (two strains), Sindbis (one strain), Barur (one strain) and two viruses which could not be characterized. Mansonia uniformis, Anopheles gambiae and Culex antennatus constituted 70% of the total collection and accounted for all of the isolates except one, which came from Anopheles funestus."}
{"id": "PMID:24294", "title": "Congenital testicular lymphangiectasis.", "content": "Testicular lymphangiectasis are described for the first time in a patient with bilateral inguinal cryptorchidism. A great number of irregular lymphatic channels was observed within the parenchyma and the tunica vasculosa in both testes. Large and numerous anastomosis between the lymphatic vessels of these two areas could also be seen. The MTD and the TFI of the left testis were normal. Both parameters were very low in the right testis. The association of this fact with the greater development of the lymphatic vessels in this testis strongly supports the idea that testicular lymphangiectasis interfere mechanically with the testis tubular development.", "contents": "Congenital testicular lymphangiectasis. Testicular lymphangiectasis are described for the first time in a patient with bilateral inguinal cryptorchidism. A great number of irregular lymphatic channels was observed within the parenchyma and the tunica vasculosa in both testes. Large and numerous anastomosis between the lymphatic vessels of these two areas could also be seen. The MTD and the TFI of the left testis were normal. Both parameters were very low in the right testis. The association of this fact with the greater development of the lymphatic vessels in this testis strongly supports the idea that testicular lymphangiectasis interfere mechanically with the testis tubular development."}
{"id": "PMID:24291", "title": "Preservation of human granulocytes. III. Liquid preservation studied by electronic sizing.", "content": "Human granulocytes were isolated from blood either by counterflow centrifugation in a Beckman JE-6 rotor or by sedimentation of the red blood cells with dextran and centrifugation of the granulocyte-rich plasma. The stability of the granulocytes was assessed during storage in the liquid state by measurements of granulocyte loss, volume distribution characteristics, and ability to produce fluorescein in their cytoplasm and to exclude ethidium bromide from their nuclei. After storage at 4 C for 2 days in phosphate-buffered saline with a pH of 7.1 containing 5 g/dl human albumin + 0.46 g/dl dextrose or 1 g/dl Physiogel + 0.46 g/dl dextrose, the granulocytes were adequately preserved from the in vitro measurements.", "contents": "Preservation of human granulocytes. III. Liquid preservation studied by electronic sizing. Human granulocytes were isolated from blood either by counterflow centrifugation in a Beckman JE-6 rotor or by sedimentation of the red blood cells with dextran and centrifugation of the granulocyte-rich plasma. The stability of the granulocytes was assessed during storage in the liquid state by measurements of granulocyte loss, volume distribution characteristics, and ability to produce fluorescein in their cytoplasm and to exclude ethidium bromide from their nuclei. After storage at 4 C for 2 days in phosphate-buffered saline with a pH of 7.1 containing 5 g/dl human albumin + 0.46 g/dl dextrose or 1 g/dl Physiogel + 0.46 g/dl dextrose, the granulocytes were adequately preserved from the in vitro measurements."}
{"id": "PMID:24295", "title": "Carcinoid tumour of the thymus. A case report including discussion of the morphological diagnosis and the cell of origin.", "content": "This report concerns a 49 year old asymptomatic male who had a mediastinal mass demonstrated on routine radiography. A large encapsulated tumour composed of small regular cells arranged in clumps and acini with fine vascular stroma was removed. The differential diagnosis on routine H&E section included parathyroid tumor, medullary carcinoma arising in ectopic thyroid tissue, epithelial thymoma or carcinoid tumor of the thymus. The presence of compressed thymic tissue around the tumor, and of argentaffin granules together with the electron microscopic appearance characteristic of the \"enterochromaffin\" or \"APUD\" group of cells allowed the diagnosis of carcinoid tumor of the thymus to be made. Electron microscopy showed that the cell cytoplasm contained electron dense membrane bound granules, together with bundles of microfilaments. Vesicles of smooth surfaced reticulum were present but rough surfaced reticulum was inconspicuous. No desmosomes were demonstrated. Special stains for amyloid and glycogen were negative.", "contents": "Carcinoid tumour of the thymus. A case report including discussion of the morphological diagnosis and the cell of origin. This report concerns a 49 year old asymptomatic male who had a mediastinal mass demonstrated on routine radiography. A large encapsulated tumour composed of small regular cells arranged in clumps and acini with fine vascular stroma was removed. The differential diagnosis on routine H&E section included parathyroid tumor, medullary carcinoma arising in ectopic thyroid tissue, epithelial thymoma or carcinoid tumor of the thymus. The presence of compressed thymic tissue around the tumor, and of argentaffin granules together with the electron microscopic appearance characteristic of the \"enterochromaffin\" or \"APUD\" group of cells allowed the diagnosis of carcinoid tumor of the thymus to be made. Electron microscopy showed that the cell cytoplasm contained electron dense membrane bound granules, together with bundles of microfilaments. Vesicles of smooth surfaced reticulum were present but rough surfaced reticulum was inconspicuous. No desmosomes were demonstrated. Special stains for amyloid and glycogen were negative."}
{"id": "PMID:24292", "title": "The effect of agitation of stored human blood on microaggregate formation.", "content": "Microaggregates (MA) composed of platelets and white blood cells form during the storage of human blood. These particles are believed to be a cause of pulmonary insufficiency in patients receiving massive blood transfusions. The present controlled study determined the effect of constant gentle agitation of CPD-anticoagulated blood, during storage at 4 C, on the formation of MA. Using a Model T Coulter Counter, it was found that agitated blood contained significantly lower volumes of MA at 7 and 14 days than did nonagitated controls. However, significant elevations, above control levels, of plasma free hemoglobin, lactic dehydrogenase, and potassium indicated significant injury to cellular components of agitated blood. This study raises serious doubts concerning the potential clinical usefulness of blood agitation during storage to prevent MA formation.", "contents": "The effect of agitation of stored human blood on microaggregate formation. Microaggregates (MA) composed of platelets and white blood cells form during the storage of human blood. These particles are believed to be a cause of pulmonary insufficiency in patients receiving massive blood transfusions. The present controlled study determined the effect of constant gentle agitation of CPD-anticoagulated blood, during storage at 4 C, on the formation of MA. Using a Model T Coulter Counter, it was found that agitated blood contained significantly lower volumes of MA at 7 and 14 days than did nonagitated controls. However, significant elevations, above control levels, of plasma free hemoglobin, lactic dehydrogenase, and potassium indicated significant injury to cellular components of agitated blood. This study raises serious doubts concerning the potential clinical usefulness of blood agitation during storage to prevent MA formation."}
{"id": "PMID:24293", "title": "[Some properties of Mg 2+, Ca 2+-AtPase of brain microsomal fractions and synaptic plasma membranes in the solubilized state].", "content": "Digitonin-solubilized Mg2+, Ca2+-ATPases of the brain microsomal fraction and synaptic plasma membranes are activated against a background of 6.0 mM Mg2+ by 0.001 and 0.03 mM of the added Ca2+ and manifest maximum activity at temperatures or 40-45 and 35-42 degrees C, respectively. The enzymes of the initial membrane preparations are activated by the same concentrations of the added Ca2+ and are characterized by the same temperature dependence. The values of pH-optima of the enzyme activity of both solubilized preparations are 7.0-7.3 and in comparison with pH-dependence of the initial membrane preparations are shifted towards acid side.", "contents": "[Some properties of Mg 2+, Ca 2+-AtPase of brain microsomal fractions and synaptic plasma membranes in the solubilized state]. Digitonin-solubilized Mg2+, Ca2+-ATPases of the brain microsomal fraction and synaptic plasma membranes are activated against a background of 6.0 mM Mg2+ by 0.001 and 0.03 mM of the added Ca2+ and manifest maximum activity at temperatures or 40-45 and 35-42 degrees C, respectively. The enzymes of the initial membrane preparations are activated by the same concentrations of the added Ca2+ and are characterized by the same temperature dependence. The values of pH-optima of the enzyme activity of both solubilized preparations are 7.0-7.3 and in comparison with pH-dependence of the initial membrane preparations are shifted towards acid side."}
{"id": "PMID:24306", "title": "The disposition of phentermine and its N-oxidized metabolic products in the rabbit.", "content": "1. When phentermine was injected intraperitoneally to rabbits, 77% of the dose was excreted in the urine within 2 days; N-oxidized metabolic products accounted for 62% dose. Major excretion products were N-hydroxyphentermine (28% dose), conjugated N-hydroxyphentermine (32% dose) and unchanged phentermine (16% dose). 2. Similarly injected N-hydroxyphentermine was excreted (62% dose) in the urine in 2 days; only 4% dose was recovered unchanged. Major routes of metabolism of N-hydroxyphentermine was conjugation (36% dose) and reduction to the parent amine (15% dose). Conditions for hydrolysis of urine to liberate N-hydroxyphentermine from its conjugates were studied; N-hydroxyphentermide decomposes in strong acid. 3. Only 10% of injected alpha, alpha-dimethyl-alpha-nitroso-beta-phenylethane was excreted in the urine in 2 days. 4. N-Oxidations is the major pathway of metabolism of phentermine in rabbits; the present results suggest that some biological activity may be mediated by the pharmacologically active N-hydroxyphentermine.", "contents": "The disposition of phentermine and its N-oxidized metabolic products in the rabbit. 1. When phentermine was injected intraperitoneally to rabbits, 77% of the dose was excreted in the urine within 2 days; N-oxidized metabolic products accounted for 62% dose. Major excretion products were N-hydroxyphentermine (28% dose), conjugated N-hydroxyphentermine (32% dose) and unchanged phentermine (16% dose). 2. Similarly injected N-hydroxyphentermine was excreted (62% dose) in the urine in 2 days; only 4% dose was recovered unchanged. Major routes of metabolism of N-hydroxyphentermine was conjugation (36% dose) and reduction to the parent amine (15% dose). Conditions for hydrolysis of urine to liberate N-hydroxyphentermine from its conjugates were studied; N-hydroxyphentermide decomposes in strong acid. 3. Only 10% of injected alpha, alpha-dimethyl-alpha-nitroso-beta-phenylethane was excreted in the urine in 2 days. 4. N-Oxidations is the major pathway of metabolism of phentermine in rabbits; the present results suggest that some biological activity may be mediated by the pharmacologically active N-hydroxyphentermine."}
{"id": "PMID:24308", "title": "[Neonatal depression in the absence of azidose (author's transl)].", "content": "In addition to those children delivered by cesarean, a noticeable number of premature infants show a neonatal depression without intrauterine or neonatal acidosis. The reasons for this are only partially known. Anesthesia, on the one hand, and the underdeveloped brain, on the other hand, are held responsible. The prognosis of these children is relatively serious. On the one hand, they show a frequent incidence of neurologic disorders, or an increased rate of deformity on the other which although without immediate intrauterine consequences, will render extrauterine life substantially more difficult, if not impossible.", "contents": "[Neonatal depression in the absence of azidose (author's transl)]. In addition to those children delivered by cesarean, a noticeable number of premature infants show a neonatal depression without intrauterine or neonatal acidosis. The reasons for this are only partially known. Anesthesia, on the one hand, and the underdeveloped brain, on the other hand, are held responsible. The prognosis of these children is relatively serious. On the one hand, they show a frequent incidence of neurologic disorders, or an increased rate of deformity on the other which although without immediate intrauterine consequences, will render extrauterine life substantially more difficult, if not impossible."}
{"id": "PMID:24309", "title": "Studies on glutamic-oxalacetic (GOT) and glutamic-pyruvic (GPT) transaminases of swine kidney worm Stephanurus dentatus (Diesing, 1839). I. Assay and general properties.", "content": "Biochemical studies on the two transaminases GOT and GPT of swine kidney worm Stephanurus dentatus have been made. GOT has been found much more active than GPT. Enzyme activities are based on the formation of oxaloacetate (GOT) or pyruvate (GPT) from aspartic acid and alanine respectively with oxoglutarate. A linear relationship is observed between the enzyme concentration and activity. GOT shows a maximum activity at pH 8.0 and Michaelis constant 9 X 10(-3) M for male and 2.9 X 10(-3) M for female. GPT has an optimum pH of 7.5 and a Michaelis constant 19 X 10(-3) M for male and 8 X 10(-3) M for female. The optimum temperature for both GOT and GPT was 60 degrees C.", "contents": "Studies on glutamic-oxalacetic (GOT) and glutamic-pyruvic (GPT) transaminases of swine kidney worm Stephanurus dentatus (Diesing, 1839). I. Assay and general properties. Biochemical studies on the two transaminases GOT and GPT of swine kidney worm Stephanurus dentatus have been made. GOT has been found much more active than GPT. Enzyme activities are based on the formation of oxaloacetate (GOT) or pyruvate (GPT) from aspartic acid and alanine respectively with oxoglutarate. A linear relationship is observed between the enzyme concentration and activity. GOT shows a maximum activity at pH 8.0 and Michaelis constant 9 X 10(-3) M for male and 2.9 X 10(-3) M for female. GPT has an optimum pH of 7.5 and a Michaelis constant 19 X 10(-3) M for male and 8 X 10(-3) M for female. The optimum temperature for both GOT and GPT was 60 degrees C."}
{"id": "PMID:24311", "title": "[The significance of serum gamma-glutamyl transpeptidase determination in the differentiation of icterus of various etiologies].", "content": "In a group of 29 patients with mechanical icterus and a control group of 38 patients (acute, chronic hepatitis and hyperbilirubinemia) there have been followed up alkaline phosphatase, leucinaminopeptidase and gammaglutamil transpeptidase activities aiming to evaluate the value of gamma GT in differentiation of icterus of various etiology. Comparing the values of the examined cholestase enzymes in patients of obstructive icterus it could be seen that gamma GT was positive in the largest percentage of the diseased, (69,6%), then APH (89,7%) AND LAP (86,3%). Gamma GT has shown to be selective test for obstruction of hepatobiliary tract but it is not selective for discovering cause of obstruction. It can be explained by the fact that activity of gamma GT could be found both in mechanical icterus caused by calculosis or tumours (with a very high activity) and in patients with hepatitis with cholestatic component, although in the decresed activity.", "contents": "[The significance of serum gamma-glutamyl transpeptidase determination in the differentiation of icterus of various etiologies]. In a group of 29 patients with mechanical icterus and a control group of 38 patients (acute, chronic hepatitis and hyperbilirubinemia) there have been followed up alkaline phosphatase, leucinaminopeptidase and gammaglutamil transpeptidase activities aiming to evaluate the value of gamma GT in differentiation of icterus of various etiology. Comparing the values of the examined cholestase enzymes in patients of obstructive icterus it could be seen that gamma GT was positive in the largest percentage of the diseased, (69,6%), then APH (89,7%) AND LAP (86,3%). Gamma GT has shown to be selective test for obstruction of hepatobiliary tract but it is not selective for discovering cause of obstruction. It can be explained by the fact that activity of gamma GT could be found both in mechanical icterus caused by calculosis or tumours (with a very high activity) and in patients with hepatitis with cholestatic component, although in the decresed activity."}
{"id": "PMID:24312", "title": "The stability properties of golden beet and red beet pigments: influence of pH, temperature, and some stabilizers.", "content": "Golden beet (Beta vulgaris var. lutea) color was found to contain 8 components, of which the most important seemed to be vulgaxanthin-I and -II. Purified vulgazanthin -I solutions are easily degraded at high temperatures. The stability is, however, strongly dependent on pH: the stability is best at pH values between 5 and 6, the poorest at low pH values, but at pH 7 the stability is better than that of betanin. Vulgaxanthin-I is more stable in the raw extract than in a purified solution. EDTA, even in ppm amounts, was found to improve the stability of betanin. The effect was dependent on pH value, being most efficient at pH 2.0 and 5.0. Stability of vulgaxanthin-I was not improved by EDTA. Tannin did not show stabilizing influence. Ascorbic acid was found to have an unfavorable influence on stability, especially in the case of betanin.", "contents": "The stability properties of golden beet and red beet pigments: influence of pH, temperature, and some stabilizers. Golden beet (Beta vulgaris var. lutea) color was found to contain 8 components, of which the most important seemed to be vulgaxanthin-I and -II. Purified vulgazanthin -I solutions are easily degraded at high temperatures. The stability is, however, strongly dependent on pH: the stability is best at pH values between 5 and 6, the poorest at low pH values, but at pH 7 the stability is better than that of betanin. Vulgaxanthin-I is more stable in the raw extract than in a purified solution. EDTA, even in ppm amounts, was found to improve the stability of betanin. The effect was dependent on pH value, being most efficient at pH 2.0 and 5.0. Stability of vulgaxanthin-I was not improved by EDTA. Tannin did not show stabilizing influence. Ascorbic acid was found to have an unfavorable influence on stability, especially in the case of betanin."}
{"id": "PMID:24313", "title": "[Dialysis technic for regulation of the internal milieu in acute poisoning].", "content": "In 72 patients with acute poisoning (15 patients without unconsciousness with 80% of acute renal and hepatic failure, and 57 patients with unconciousness with 10.5% of acute renal and hepatic failure) the significance of the continuous prolonged haemodialysis lasting on an average 12 hours, respectively 18 hours, with the maximum of 33 and 82 hour, respectively. The duration of the haemodialysis was in close correlation with the pH-value of the blood and the duration of the unconciousness. One half of the unconscious patients suffered from dehydration (of them up to 40.3%), which was valuated by the height of the central venous blood pressure. It was also referred to the necessity of the correction of the potassiaemia and glycaemia.", "contents": "[Dialysis technic for regulation of the internal milieu in acute poisoning]. In 72 patients with acute poisoning (15 patients without unconsciousness with 80% of acute renal and hepatic failure, and 57 patients with unconciousness with 10.5% of acute renal and hepatic failure) the significance of the continuous prolonged haemodialysis lasting on an average 12 hours, respectively 18 hours, with the maximum of 33 and 82 hour, respectively. The duration of the haemodialysis was in close correlation with the pH-value of the blood and the duration of the unconciousness. One half of the unconscious patients suffered from dehydration (of them up to 40.3%), which was valuated by the height of the central venous blood pressure. It was also referred to the necessity of the correction of the potassiaemia and glycaemia."}
{"id": "PMID:24314", "title": "[Current status of treatment of parasellar meningiomas].", "content": "For 302 patients presenting the respective indication in the years 1968 to 1972 the operation lethality amounted to 24.8%. Then the microtechnique including the operation microscope were introduced. Out of 47 cases of tuberculum sellae meningiomas one patient died; out of 42 patients suffering from median meningiomas of the wing of the sphenoid bone nine died. Lethality decreased by one half, radical surgery increased from 50 to 80 to 85%. A contraindication for surgery was not considered to be present even with a bad general condition. Post-operative control: cerebrospinal pressure, intracerebral pressure, pressure of the interstitial fluid, local and regional blood supply, pO2 and pCO2, electrolyte balance, pH, osmolality. This allowed also to record conditions of underpressure.", "contents": "[Current status of treatment of parasellar meningiomas]. For 302 patients presenting the respective indication in the years 1968 to 1972 the operation lethality amounted to 24.8%. Then the microtechnique including the operation microscope were introduced. Out of 47 cases of tuberculum sellae meningiomas one patient died; out of 42 patients suffering from median meningiomas of the wing of the sphenoid bone nine died. Lethality decreased by one half, radical surgery increased from 50 to 80 to 85%. A contraindication for surgery was not considered to be present even with a bad general condition. Post-operative control: cerebrospinal pressure, intracerebral pressure, pressure of the interstitial fluid, local and regional blood supply, pO2 and pCO2, electrolyte balance, pH, osmolality. This allowed also to record conditions of underpressure."}
{"id": "PMID:24315", "title": "[Genital disorders that influence fertility and potency. Screening methods].", "content": "It is recommended to introduce screening for fertility and potency determination to disclose genital disturbances the correction of which must be done in childhood or early age. Cryptorchism, undescended testicles or their hypoplasia, hypogonadism, hypogenitalism, hypospadias and finally varicocele are easily detected by screening at school, on military enlistment or by the sports physician.", "contents": "[Genital disorders that influence fertility and potency. Screening methods]. It is recommended to introduce screening for fertility and potency determination to disclose genital disturbances the correction of which must be done in childhood or early age. Cryptorchism, undescended testicles or their hypoplasia, hypogonadism, hypogenitalism, hypospadias and finally varicocele are easily detected by screening at school, on military enlistment or by the sports physician."}
{"id": "PMID:24317", "title": "Changes in serum TSH level after intraventricular injection of various neuromediators in rats.", "content": "The influence of various neuromediators on pituitary TSH secretion in rats has been investigated. Noradrenaline 50 microgram/rat, dopamine 50 microgram/rat, serotonine-creatinine-sulphate 100 micogram/rat, gamma-aminobutyric acid 100 microgram/rat, pilocarpine 1 mg/rat, histamine 100 microgram/rat were administered into the lateral ventricle of the brain. All agents were dissolved in Parker's fluid. Two control groups of animals were given Parker's fluid and subjected to surgical manipulations, respectively. Plasma TSH level was estimated after 30 min by means of radioimmunoassay. The increase in the TSH level was observed after the injection of serotonine and noradrenaline (4.0 and 3.1 ng/ml, respectively) as compared with control group (0.7 ng/ml).", "contents": "Changes in serum TSH level after intraventricular injection of various neuromediators in rats. The influence of various neuromediators on pituitary TSH secretion in rats has been investigated. Noradrenaline 50 microgram/rat, dopamine 50 microgram/rat, serotonine-creatinine-sulphate 100 micogram/rat, gamma-aminobutyric acid 100 microgram/rat, pilocarpine 1 mg/rat, histamine 100 microgram/rat were administered into the lateral ventricle of the brain. All agents were dissolved in Parker's fluid. Two control groups of animals were given Parker's fluid and subjected to surgical manipulations, respectively. Plasma TSH level was estimated after 30 min by means of radioimmunoassay. The increase in the TSH level was observed after the injection of serotonine and noradrenaline (4.0 and 3.1 ng/ml, respectively) as compared with control group (0.7 ng/ml)."}
{"id": "PMID:24318", "title": "ATP-induced release of vasopressin associated with phosphorylation of isolated bovine neurohypophyseal secretory granule membranes.", "content": "Secretory granules isolated from ox neurohypophyses released their content of vasopressin in the presence of ATP and Mg2+. A half maximal ATP concentration of 0.25 mM was found. Ca2+ was not necessary for the effect. High concentrations of ADP, AMP and ITP were shown to mimic the effect of ATP. Utilizing this effect of ATP combined with iodonitrotetrazolium treatment to make mitochondria heavier, a method is described to obtain granule \"ghosts\" in a purified form. They were shown to be phosphorylated when granules were incubated with [gamma-32P] ATP.", "contents": "ATP-induced release of vasopressin associated with phosphorylation of isolated bovine neurohypophyseal secretory granule membranes. Secretory granules isolated from ox neurohypophyses released their content of vasopressin in the presence of ATP and Mg2+. A half maximal ATP concentration of 0.25 mM was found. Ca2+ was not necessary for the effect. High concentrations of ADP, AMP and ITP were shown to mimic the effect of ATP. Utilizing this effect of ATP combined with iodonitrotetrazolium treatment to make mitochondria heavier, a method is described to obtain granule \"ghosts\" in a purified form. They were shown to be phosphorylated when granules were incubated with [gamma-32P] ATP."}
{"id": "PMID:24319", "title": "Evaluation of the usefulness of serum gamma-glutamyl transpeptidase levels in the management of haematological neoplasia.", "content": "The levels of serum gamma-glutamyl transpeptidase (GGT) and, when appropriate, alkaline phosphatase (AP) and 5'-nucleotidase (NTD) have been measured as a routine in 276 patients with malignant haematological diseases during a 26-month trial period. GGT levels add no prognostic information to the routine haematological surveillance of leukaemia. Polychemotherapy does not appear to be an inducer of liver drug-metabolising microsomal enzymes. Polycythaemia rubra vera, myelofibrosis and chronic lymphocytic leukaemia may cause little change in GGT, AP and NTD levels despite marked hepatomegaly. A raised GGT in Hodgkin's disease and non-Hodgkin lymphoma is generally associated with active and widespread disease, but not necessarily a sign of malignant tissue in the liver. The elevations of GGT in myeloma may be secondary to liver infiltration though this group merits further detailed study.", "contents": "Evaluation of the usefulness of serum gamma-glutamyl transpeptidase levels in the management of haematological neoplasia. The levels of serum gamma-glutamyl transpeptidase (GGT) and, when appropriate, alkaline phosphatase (AP) and 5'-nucleotidase (NTD) have been measured as a routine in 276 patients with malignant haematological diseases during a 26-month trial period. GGT levels add no prognostic information to the routine haematological surveillance of leukaemia. Polychemotherapy does not appear to be an inducer of liver drug-metabolising microsomal enzymes. Polycythaemia rubra vera, myelofibrosis and chronic lymphocytic leukaemia may cause little change in GGT, AP and NTD levels despite marked hepatomegaly. A raised GGT in Hodgkin's disease and non-Hodgkin lymphoma is generally associated with active and widespread disease, but not necessarily a sign of malignant tissue in the liver. The elevations of GGT in myeloma may be secondary to liver infiltration though this group merits further detailed study."}
{"id": "PMID:24320", "title": "\"False positive\" acidified serum test in a preleukemic dyserythropoiesis.", "content": "In a case of preleukemic dyserythropoiesis, in vitro red cell lysis tests showed a positive acidified serum test whose characteristics are described. The positive acidified serum test occurred in 10 normal sera, in 1 serum with complete deficiency of the fourth component of complement and in 1 serum with complete deficiency of the second component of complement. The test was found negative with 2 hyperlipemic sera. The other in vitro red-cell lysis tests were negative. The results of the in vitro lysis tests were different from the results obtained in paroxysmal nocturnal hemoglobinuria and congenital dyserythropoietic anemias.", "contents": "\"False positive\" acidified serum test in a preleukemic dyserythropoiesis. In a case of preleukemic dyserythropoiesis, in vitro red cell lysis tests showed a positive acidified serum test whose characteristics are described. The positive acidified serum test occurred in 10 normal sera, in 1 serum with complete deficiency of the fourth component of complement and in 1 serum with complete deficiency of the second component of complement. The test was found negative with 2 hyperlipemic sera. The other in vitro red-cell lysis tests were negative. The results of the in vitro lysis tests were different from the results obtained in paroxysmal nocturnal hemoglobinuria and congenital dyserythropoietic anemias."}
{"id": "PMID:24323", "title": "Pharmacokinetics of 2-pivaloylindan-1,3-dione in dogs.", "content": "The pharmacokinetics of 2-pivaloylindan-1,3-dione (Pival) after administration of a single dose was investigated in dogs. The plasma concentration graph can be described by a one compartment open model. The drug is fairly well adsorbed (67%) and the excretion is extremely slow with a half-life of nearly five days. These kinetics can be explained by the physiochemical properties of the drug, such as strong binding to canine plasma protein, high lipophility and the lack of transformation to polar metabolites. A single oral dose of 5 mg/kg must be regarded as lethal to dogs and the LD50 is assumed to be approximately 4 mg/kg in this species.", "contents": "Pharmacokinetics of 2-pivaloylindan-1,3-dione in dogs. The pharmacokinetics of 2-pivaloylindan-1,3-dione (Pival) after administration of a single dose was investigated in dogs. The plasma concentration graph can be described by a one compartment open model. The drug is fairly well adsorbed (67%) and the excretion is extremely slow with a half-life of nearly five days. These kinetics can be explained by the physiochemical properties of the drug, such as strong binding to canine plasma protein, high lipophility and the lack of transformation to polar metabolites. A single oral dose of 5 mg/kg must be regarded as lethal to dogs and the LD50 is assumed to be approximately 4 mg/kg in this species."}
{"id": "PMID:24324", "title": "Minoxidil in severe hypertension.", "content": "Minoxidil has been administered to 16 patients with severe hypertension and renal failure. In every patient the indication for minoxidil treatment was resistance to conventional drugs. The final dose of minoxidil was 2.5--30 mg (average 20) and it was combined with a beta-blocking agent and a diuretic (or dialysis). The therapy was given for 1--27 months (average 12). The average supine BP fell from 200/130 to 164/96 mmHg and the upright BP from 200/120 to 152/90 mmHg. No hypotensive reactions occurred. In most patients the progression of hypertensive organ changes was arrested. No major vascular complications have occurred during the 16 years of treatment. Prickling of the skin and hirsutism were common side-effects. The other side-effects observed were oedema in five patients and development of latent diabetes in three. In four patients minoxidil treatment was discontinued for following reasons: successful reconstruction of the renal artery after stenosis, renal transplantation, severe oedema and hirsutism. The risk of hirsutism is a contraindication to prolonged minoxidil administration in most femal patients. Minoxidil is especially indicated in uncontrolled renal hypertension.", "contents": "Minoxidil in severe hypertension. Minoxidil has been administered to 16 patients with severe hypertension and renal failure. In every patient the indication for minoxidil treatment was resistance to conventional drugs. The final dose of minoxidil was 2.5--30 mg (average 20) and it was combined with a beta-blocking agent and a diuretic (or dialysis). The therapy was given for 1--27 months (average 12). The average supine BP fell from 200/130 to 164/96 mmHg and the upright BP from 200/120 to 152/90 mmHg. No hypotensive reactions occurred. In most patients the progression of hypertensive organ changes was arrested. No major vascular complications have occurred during the 16 years of treatment. Prickling of the skin and hirsutism were common side-effects. The other side-effects observed were oedema in five patients and development of latent diabetes in three. In four patients minoxidil treatment was discontinued for following reasons: successful reconstruction of the renal artery after stenosis, renal transplantation, severe oedema and hirsutism. The risk of hirsutism is a contraindication to prolonged minoxidil administration in most femal patients. Minoxidil is especially indicated in uncontrolled renal hypertension."}
{"id": "PMID:24327", "title": "Histamine H2-receptor antagonists.", "content": "Development of histamine H2-receptor antagonists has enhanced the understanding of histamine physiology and pharmacology. The effect of H2-receptor antagonists on gastrointestinal physiology has been studied extensively. These compounds inhibit gastric acid secretion in response to all known secretagogues and, in contrast to anticholinergic drugs, markedly inhibit food-stimulated acid secretion in duodenal ulcer patients. The relative roles of H2-receptor antagonists, anticholinergic drugs and antacids in the treatment of duodenal ulcer remain to be defined. Cimetidine currently is under investigation for the treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, gastrointestinal bleeding and hypersecretory states. Although the long-term safety of cimetidine has not been established, in short-term clinical trials there have been no significant subjective or objective side-effects. Assuming that toxic effects do not develop, H2-receptor antagonists should improve the treatment of acid-peptic disease.", "contents": "Histamine H2-receptor antagonists. Development of histamine H2-receptor antagonists has enhanced the understanding of histamine physiology and pharmacology. The effect of H2-receptor antagonists on gastrointestinal physiology has been studied extensively. These compounds inhibit gastric acid secretion in response to all known secretagogues and, in contrast to anticholinergic drugs, markedly inhibit food-stimulated acid secretion in duodenal ulcer patients. The relative roles of H2-receptor antagonists, anticholinergic drugs and antacids in the treatment of duodenal ulcer remain to be defined. Cimetidine currently is under investigation for the treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, gastrointestinal bleeding and hypersecretory states. Although the long-term safety of cimetidine has not been established, in short-term clinical trials there have been no significant subjective or objective side-effects. Assuming that toxic effects do not develop, H2-receptor antagonists should improve the treatment of acid-peptic disease."}
{"id": "PMID:24329", "title": "Biodistribution of salicylates: a clue to the understanding of some effects and side effects.", "content": "According to our concept that biodistribution of salicylates (SA) might be an important factor of their mode of action the distribution of sodiumsalicylate (NaSA) and acetylsalicylic acid (ASA) was investigated in vivo and in vitro. It was shown that particular high concentrations of both compounds were found in vivo in the glandular stomach region and the kidney tubules of rats as well as in inflamed tissue. Quantitative studies showed that in chicken, in inflamed joints, higher concentrations as in plasma and about three times higher concentrations as in control joints were observed. In vitro studies using human erythrocytes suspended in buffer of different pH showed that added NaSA accumulated in these cells when the environmental pH was lowered from 7.4 to 6.8. From these results it is speculated that SA being weak acids accumulate within cells which are surrounded or bordering acidic fluids. This is the case in the stomach, the kidney and the inflamed tissue. This is where SA exert their effects and side effects.", "contents": "Biodistribution of salicylates: a clue to the understanding of some effects and side effects. According to our concept that biodistribution of salicylates (SA) might be an important factor of their mode of action the distribution of sodiumsalicylate (NaSA) and acetylsalicylic acid (ASA) was investigated in vivo and in vitro. It was shown that particular high concentrations of both compounds were found in vivo in the glandular stomach region and the kidney tubules of rats as well as in inflamed tissue. Quantitative studies showed that in chicken, in inflamed joints, higher concentrations as in plasma and about three times higher concentrations as in control joints were observed. In vitro studies using human erythrocytes suspended in buffer of different pH showed that added NaSA accumulated in these cells when the environmental pH was lowered from 7.4 to 6.8. From these results it is speculated that SA being weak acids accumulate within cells which are surrounded or bordering acidic fluids. This is the case in the stomach, the kidney and the inflamed tissue. This is where SA exert their effects and side effects."}
{"id": "PMID:24330", "title": "Renal excretion of fluid, electrolytes and hydrogen ions before and during diamox administration in healthy Nigerians.", "content": "Twenty-four urine specimens of eleven healthy Nigerians taken during the cool rainy season, were examined before and during diamox (acetazolamide) administration. Mean control volume-output was 1.4 litres containing 109.5 mEq Na+, 46.6 mEq K+ and 120 mEq Cl- ions. Total renal acid excretion was 36.82 partitioned as 14.72 mEq titratable buffer-acid and 22.1 mEq ammonia. During diamox intake, volume-output increased to 2.56 litres with Na+ and K+ contents of 222.4 and 107 mEq respectively, whilst Cl- ions, fell to 2.6 mEq. Daily renal acid excretion was reduced by 25% and titratable buffer acid was absent in most samples but ammonia excretion showed a wide scatter with a range of 6.5-60.8 mEq. The probable explanations for the lower potassium and total acid excretions during the control period as well as the pattern of ammonia excretion during diamox therapy are discussed.", "contents": "Renal excretion of fluid, electrolytes and hydrogen ions before and during diamox administration in healthy Nigerians. Twenty-four urine specimens of eleven healthy Nigerians taken during the cool rainy season, were examined before and during diamox (acetazolamide) administration. Mean control volume-output was 1.4 litres containing 109.5 mEq Na+, 46.6 mEq K+ and 120 mEq Cl- ions. Total renal acid excretion was 36.82 partitioned as 14.72 mEq titratable buffer-acid and 22.1 mEq ammonia. During diamox intake, volume-output increased to 2.56 litres with Na+ and K+ contents of 222.4 and 107 mEq respectively, whilst Cl- ions, fell to 2.6 mEq. Daily renal acid excretion was reduced by 25% and titratable buffer acid was absent in most samples but ammonia excretion showed a wide scatter with a range of 6.5-60.8 mEq. The probable explanations for the lower potassium and total acid excretions during the control period as well as the pattern of ammonia excretion during diamox therapy are discussed."}
{"id": "PMID:24332", "title": "Orungo virus, an orbivirus from Africa: effects of physical and chemical agents.", "content": "Orungo virus is relatively sensitive to lipid solvents and sodium deoxycholate. It is readily inactivated at 37 degrees C and above, by u.v. irradiation, BP and formalin. Orungo virus is ph 3.0 labile, but stable at ph range of 5.0-7.0. Multiplication of Orungo virus in BHK-21 cell cultures is not affected in the presence of 5-iododeoxyuridine.", "contents": "Orungo virus, an orbivirus from Africa: effects of physical and chemical agents. Orungo virus is relatively sensitive to lipid solvents and sodium deoxycholate. It is readily inactivated at 37 degrees C and above, by u.v. irradiation, BP and formalin. Orungo virus is ph 3.0 labile, but stable at ph range of 5.0-7.0. Multiplication of Orungo virus in BHK-21 cell cultures is not affected in the presence of 5-iododeoxyuridine."}
{"id": "PMID:24334", "title": "Pulmonary function following feeding in low-birth-weight infants.", "content": "Determination of functional residual capacity, arterial gas tensions and pH, and arterial-alveolar differences was carried out in a group of nondistressed premature infants to determine if significant alterations in lung volumes or ventilation perfusion relationships sufficiently large to cause cyanosis could be detected after feeding. The only statistically significant changes observed in these parameters were immediately following feeding, a fall of .01 pH units and a fall of 6 mm Hg in arterial oxygen tension; and 15 minutes after feeding, a fall of .01 pH units and a rise in arterial PCO2 of 3 mm Hg. In addition, significant falls in peripheral blood flow were observed five minutes after feeding in association with marked elevations in peripheral vascular resistance. The mild impairment in pulmonary function in association with the more profound changes in limb blood flow are consistent with other studies in premature and full-term infants. These data suggest that cyanotic attacks following feeding may have a complex etiology and require an aggressive multisystem approach for adequate diagnosis and therapy.", "contents": "Pulmonary function following feeding in low-birth-weight infants. Determination of functional residual capacity, arterial gas tensions and pH, and arterial-alveolar differences was carried out in a group of nondistressed premature infants to determine if significant alterations in lung volumes or ventilation perfusion relationships sufficiently large to cause cyanosis could be detected after feeding. The only statistically significant changes observed in these parameters were immediately following feeding, a fall of .01 pH units and a fall of 6 mm Hg in arterial oxygen tension; and 15 minutes after feeding, a fall of .01 pH units and a rise in arterial PCO2 of 3 mm Hg. In addition, significant falls in peripheral blood flow were observed five minutes after feeding in association with marked elevations in peripheral vascular resistance. The mild impairment in pulmonary function in association with the more profound changes in limb blood flow are consistent with other studies in premature and full-term infants. These data suggest that cyanotic attacks following feeding may have a complex etiology and require an aggressive multisystem approach for adequate diagnosis and therapy."}
{"id": "PMID:24335", "title": "Toxic epidermal necrolysis from graft-vs-host disease. Occurrence in a patient with thymic hypoplasia.", "content": "An infant with diarrhea, failure to thrive, and a seborrhea-like skin eruption was thought to have fatal familial Leiner's syndrome. Treatment with nonirradiated plasma was followed by graft-vs-host disease and fatal toxic epidermal necrolysis; thymic hypoplasia was found at autopsy. Accurate diagnosis of immunodeficiency syndromes is essential to avoid potentially harmful therapy.", "contents": "Toxic epidermal necrolysis from graft-vs-host disease. Occurrence in a patient with thymic hypoplasia. An infant with diarrhea, failure to thrive, and a seborrhea-like skin eruption was thought to have fatal familial Leiner's syndrome. Treatment with nonirradiated plasma was followed by graft-vs-host disease and fatal toxic epidermal necrolysis; thymic hypoplasia was found at autopsy. Accurate diagnosis of immunodeficiency syndromes is essential to avoid potentially harmful therapy."}
{"id": "PMID:24337", "title": "Diagnosis and treatment of diffuse ileojejunitis.", "content": "Thirteen patients with diffuse ileojejunitis have been diagnosed and treated by us over the past ten years. The disease bears close resemblance to Crohn's disease and may represent a variant of it. No clearcut relationship to celiac sprue was observed in this group of patients. Therapeutic success was obtained in the majority of patients treated with the anti-inflammatory drugs, sulfasalazine and steroids, with four patients requiring resectional surgery, all others manageable by nonsurgical means. There was no mortality in this series of patients.", "contents": "Diagnosis and treatment of diffuse ileojejunitis. Thirteen patients with diffuse ileojejunitis have been diagnosed and treated by us over the past ten years. The disease bears close resemblance to Crohn's disease and may represent a variant of it. No clearcut relationship to celiac sprue was observed in this group of patients. Therapeutic success was obtained in the majority of patients treated with the anti-inflammatory drugs, sulfasalazine and steroids, with four patients requiring resectional surgery, all others manageable by nonsurgical means. There was no mortality in this series of patients."}
{"id": "PMID:24338", "title": "H2 receptor antagonists.", "content": "The uses of the histamine H2 receptor antagonists (H2 antagonists) in the management of peptic ulcer disease and the Zollinger-Ellison syndrome are reviewed. Drugs included in the discussion are burimamide, metiamide and cimetidine. The secretion and the pharmacology of the H2 antagonists are described. A discussion of the clinical use of the H2 receptor antagonists in the treatment of gastric hyperacidity and hypersecretory states, and the side effects encountered is presented. Cimetidine is effective in the treatment of duodenal ulcer, and its use appears promising in Zollinger-Ellison syndrome and gastric ulceration.", "contents": "H2 receptor antagonists. The uses of the histamine H2 receptor antagonists (H2 antagonists) in the management of peptic ulcer disease and the Zollinger-Ellison syndrome are reviewed. Drugs included in the discussion are burimamide, metiamide and cimetidine. The secretion and the pharmacology of the H2 antagonists are described. A discussion of the clinical use of the H2 receptor antagonists in the treatment of gastric hyperacidity and hypersecretory states, and the side effects encountered is presented. Cimetidine is effective in the treatment of duodenal ulcer, and its use appears promising in Zollinger-Ellison syndrome and gastric ulceration."}
{"id": "PMID:24339", "title": "Pharmacists' knowledge and attitudes regarding monitoring the behaviors of children with learning disabilities.", "content": "The attitudes and knowledge of pharmacists in Nebraska regarding children's learning disabilities were surveyed by questionnaire. One hundred thirty-three pharmacists responded. The results were analyzed according to type of practice (community, chain and hospital) and age (20--30 years, 31--40 years, 41--50 years, and 51 years and over). The results indicate that pharmacists are being asked about learning disabilities. Overall, 53% of the pharmacists responding had been asked about learning disabilities by parents, physicians, teachers or others. No significant interactions were found between the type of practice and age, and no significant main effect for type of practice was found in the ANOVA results for knowledge scores or attitude scores. Even though there were no differences owing to age in pharmacists' knowledge of learning disabilities, age was found to have a significant effect on attitudes toward increased pharmacist involvement in monitoring behaviors of learning-disabled children; the younger groups had a more positive attitude. The pharmacist seems to have the knowledge and attitudes required to become more actively involved in monitoring the medications and behaviors of children with learning disabilities.", "contents": "Pharmacists' knowledge and attitudes regarding monitoring the behaviors of children with learning disabilities. The attitudes and knowledge of pharmacists in Nebraska regarding children's learning disabilities were surveyed by questionnaire. One hundred thirty-three pharmacists responded. The results were analyzed according to type of practice (community, chain and hospital) and age (20--30 years, 31--40 years, 41--50 years, and 51 years and over). The results indicate that pharmacists are being asked about learning disabilities. Overall, 53% of the pharmacists responding had been asked about learning disabilities by parents, physicians, teachers or others. No significant interactions were found between the type of practice and age, and no significant main effect for type of practice was found in the ANOVA results for knowledge scores or attitude scores. Even though there were no differences owing to age in pharmacists' knowledge of learning disabilities, age was found to have a significant effect on attitudes toward increased pharmacist involvement in monitoring behaviors of learning-disabled children; the younger groups had a more positive attitude. The pharmacist seems to have the knowledge and attitudes required to become more actively involved in monitoring the medications and behaviors of children with learning disabilities."}
{"id": "PMID:24341", "title": "Development of neurohumoral control of fetal, neonatal, and adult cardiovascular functions.", "content": "Neurohumoral control of fetal, neonatal, and adult cardiovascular functions have been reviewed. Resting fetal heart rate remains fairly constant but neonatal heart rate declines progressively, reaching adult levels within six to eight weeks; systemic arterial pressure rises while pulmonary pressure falls to adult levels within the first week after birth. Sympathetic and parasympathetic control of circulatory functions matures at different rates during fetal and neonatal development; the sympathetic system becomes active earlier in fetal life than does the parasympathetic system. After birth, the parasympathetic tone of the resting heart rate rises to adult levels while adrenergic tone decreases. Despite changing autonomic activities, resting heart rate is set at given levels through alterations in intrinsic control. In the fetus, peripheral circulation is under neurohumoral tone of increasing magnitude; after birth, neurohumoral tone declines progressively, reaching levels comparable to those of adult nonpregnant sheep. Fetal cardiovascular response to neurotransmitters increases with age because of maturation of the effector system. The pulmonary bed responds primarily to acetylcholine whereas the systemic circulation responds to norepinephrine. After birth, the neonatal cardiovascular system becomes four to five times more sensitive to the action of neurotransmitters mainly because of closure of vascular shunts and elimination of umbilicoplacental circulation. In the neonate and adult, the pulmonary vascular bed loses its reactivity to neurotransmitters.", "contents": "Development of neurohumoral control of fetal, neonatal, and adult cardiovascular functions. Neurohumoral control of fetal, neonatal, and adult cardiovascular functions have been reviewed. Resting fetal heart rate remains fairly constant but neonatal heart rate declines progressively, reaching adult levels within six to eight weeks; systemic arterial pressure rises while pulmonary pressure falls to adult levels within the first week after birth. Sympathetic and parasympathetic control of circulatory functions matures at different rates during fetal and neonatal development; the sympathetic system becomes active earlier in fetal life than does the parasympathetic system. After birth, the parasympathetic tone of the resting heart rate rises to adult levels while adrenergic tone decreases. Despite changing autonomic activities, resting heart rate is set at given levels through alterations in intrinsic control. In the fetus, peripheral circulation is under neurohumoral tone of increasing magnitude; after birth, neurohumoral tone declines progressively, reaching levels comparable to those of adult nonpregnant sheep. Fetal cardiovascular response to neurotransmitters increases with age because of maturation of the effector system. The pulmonary bed responds primarily to acetylcholine whereas the systemic circulation responds to norepinephrine. After birth, the neonatal cardiovascular system becomes four to five times more sensitive to the action of neurotransmitters mainly because of closure of vascular shunts and elimination of umbilicoplacental circulation. In the neonate and adult, the pulmonary vascular bed loses its reactivity to neurotransmitters."}
{"id": "PMID:24342", "title": "Immune complexes of hepatitis B surface antigen in the pathogenesis of periarteritis nodosa. A study of seven necropsy cases.", "content": "In 7 unselected necropsy cases of clinically diagnosed periarteritis nodosa, the detection of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the cytoplasm and nuclei of hepatocytes indicated an ongoing infection with hepititis B virus (HBV). In all these cases histologic changes found in the liver varied from \"minimal\" to chronic aggressive hepatitis. In all the cases, deposits of HBsAg, immunoglobulins, beta1C-globulin and C1q were detected in vascular lesions. That these deposits could represent HBsAg-anti-HBs immune complexes was supported by demonstrating their strong binding of guinea pig complement and by the successful elution of all HBsAg and part of the immunoglobulin from these deposits by treatment with buffers known to dissociate antigen-antibody bonds but not with phosphate-buffered saline, pH 7.6 (PBS). Glomerulonephritis associated with these immune complexes was found in 6 cases. The presence of larger masses of HBsAg immune complexes, chiefly in recent insudative and fibrinoid vascular lesions, their lesser amounts in lesions undergoing involution, and their absence from healed lesions strongly suggest that these complexes play a primary role in the pathogenesis of acute vascular damage in periarteritis nodosa.", "contents": "Immune complexes of hepatitis B surface antigen in the pathogenesis of periarteritis nodosa. A study of seven necropsy cases. In 7 unselected necropsy cases of clinically diagnosed periarteritis nodosa, the detection of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the cytoplasm and nuclei of hepatocytes indicated an ongoing infection with hepititis B virus (HBV). In all these cases histologic changes found in the liver varied from \"minimal\" to chronic aggressive hepatitis. In all the cases, deposits of HBsAg, immunoglobulins, beta1C-globulin and C1q were detected in vascular lesions. That these deposits could represent HBsAg-anti-HBs immune complexes was supported by demonstrating their strong binding of guinea pig complement and by the successful elution of all HBsAg and part of the immunoglobulin from these deposits by treatment with buffers known to dissociate antigen-antibody bonds but not with phosphate-buffered saline, pH 7.6 (PBS). Glomerulonephritis associated with these immune complexes was found in 6 cases. The presence of larger masses of HBsAg immune complexes, chiefly in recent insudative and fibrinoid vascular lesions, their lesser amounts in lesions undergoing involution, and their absence from healed lesions strongly suggest that these complexes play a primary role in the pathogenesis of acute vascular damage in periarteritis nodosa."}
{"id": "PMID:24343", "title": "Tumor induction in host-versus-graft disease. I. Clinical and pathologic features.", "content": "Perinatal C57BL/1 mice given injections of (SJL/J X C57BL/1)F1 spleen cells developed a highly lethal runting syndrome, designated host-versus-graft disease (HVGD). The mortality was related to the dosage of F1 cells. Acute pathologic changes resembled those occurring in parent leads to F1 graft-versus-host disease (GVHD), except for more pronounced plasmacytosis. Mice suffering from HVGD recovered clinically with no sequelae except for a slight increase in  the incidence of lymphomas over control mice. Such mice were hyperreactive to F1 cells utilized to initiate the original HVGD syndrome. Most of the tumors developed in those animals receiving the initial injection of F1 spleen cells within 24 hours of birth. Tumor incidence was unrelated to the clinical severity of HVGD. By contrast, GVHD in the same strain combination resulted in a much higher incidence of lymphomas in a much shorter time. Parental strain cells were detectable in the F1 hosts up to the time of tumor development. HVGD has a low tumor induction potential; GVHD has a high tumor induction potential.", "contents": "Tumor induction in host-versus-graft disease. I. Clinical and pathologic features. Perinatal C57BL/1 mice given injections of (SJL/J X C57BL/1)F1 spleen cells developed a highly lethal runting syndrome, designated host-versus-graft disease (HVGD). The mortality was related to the dosage of F1 cells. Acute pathologic changes resembled those occurring in parent leads to F1 graft-versus-host disease (GVHD), except for more pronounced plasmacytosis. Mice suffering from HVGD recovered clinically with no sequelae except for a slight increase in  the incidence of lymphomas over control mice. Such mice were hyperreactive to F1 cells utilized to initiate the original HVGD syndrome. Most of the tumors developed in those animals receiving the initial injection of F1 spleen cells within 24 hours of birth. Tumor incidence was unrelated to the clinical severity of HVGD. By contrast, GVHD in the same strain combination resulted in a much higher incidence of lymphomas in a much shorter time. Parental strain cells were detectable in the F1 hosts up to the time of tumor development. HVGD has a low tumor induction potential; GVHD has a high tumor induction potential."}
{"id": "PMID:24345", "title": "Association of increased pHi with calcium ion release in skeletal muscle.", "content": "The pH difference across the cell membrane of frog sartorius muscle cells was measured with the distribution of 5,5-dimethyl-2,4-oxazolidine-dione (DMO) as the marker. Depolarization of the muscles to values at or below the contraction threshold caused by elevating external potassium up to approximately 20 mM resulted in an internal alkalinization. The change was smaller with superthreshold depolarization (20--30 mM [K+]). The alkalinization was blocked by agents that block calcium release from the sarcoplasmic reticulum (procaine and dantrolene sodium). Other agents that cause calcium release (caffeine, theophylline, and quinine) were found to give alkalinization when tested at concentrations just below the contracture threshold. Increased acidification of the extracellular medium was associated with the internal alkalinization. The data were interpreted as indicating the presence of a calcium-stimulated H+ and/or OH- ion transport system in the muscle membrane.", "contents": "Association of increased pHi with calcium ion release in skeletal muscle. The pH difference across the cell membrane of frog sartorius muscle cells was measured with the distribution of 5,5-dimethyl-2,4-oxazolidine-dione (DMO) as the marker. Depolarization of the muscles to values at or below the contraction threshold caused by elevating external potassium up to approximately 20 mM resulted in an internal alkalinization. The change was smaller with superthreshold depolarization (20--30 mM [K+]). The alkalinization was blocked by agents that block calcium release from the sarcoplasmic reticulum (procaine and dantrolene sodium). Other agents that cause calcium release (caffeine, theophylline, and quinine) were found to give alkalinization when tested at concentrations just below the contracture threshold. Increased acidification of the extracellular medium was associated with the internal alkalinization. The data were interpreted as indicating the presence of a calcium-stimulated H+ and/or OH- ion transport system in the muscle membrane."}
{"id": "PMID:24346", "title": "Na+ transport by mammalian stomach.", "content": "Gastric mucosas from newborn pigs (0--20 days) and rabbits (0--20 days) were used for in vitro investigation of active Na+ transport during resting (no HCl secretion) conditions. As measured with 22Na+, these tissues actively absorb Na+ from the mucosal-to serosal (m-t-s) bathing solution during both open-circuit and short-circuit current (Is) conditions. In the nonsecreting state, net Na+ transport accounts for 40--60% of Isc. The remaining current is provided by net s-to-m flux of Cl-. Amiloride (2-5 X 10(-5) M) in the mucosal solution abolishes this active Na+ transport by inhibiting m-to-s fluxes of Na+ (JNams). In vivo-in vitro experiments showed that active Na+ transport is a normal function of the resting mammalian stomach. Decreasing pH of the mucosal solution below pH 5 reversibly causes decreased current-generating capability of the tissue. Pretreatment of the tissue with amiloride abolishes this pH effect. The implication is that the low pH affects the Na+-entry step into cells. \"Titration curves\" of current vs. pH had an apparent pK approximately 4.0. Ouabain and K+-free solutions both cause decreases in active Na+ and Cl- current. Calculations indicate that a shunt may account for only a small (less than 30%) percentage of total transepithelial conductance.", "contents": "Na+ transport by mammalian stomach. Gastric mucosas from newborn pigs (0--20 days) and rabbits (0--20 days) were used for in vitro investigation of active Na+ transport during resting (no HCl secretion) conditions. As measured with 22Na+, these tissues actively absorb Na+ from the mucosal-to serosal (m-t-s) bathing solution during both open-circuit and short-circuit current (Is) conditions. In the nonsecreting state, net Na+ transport accounts for 40--60% of Isc. The remaining current is provided by net s-to-m flux of Cl-. Amiloride (2-5 X 10(-5) M) in the mucosal solution abolishes this active Na+ transport by inhibiting m-to-s fluxes of Na+ (JNams). In vivo-in vitro experiments showed that active Na+ transport is a normal function of the resting mammalian stomach. Decreasing pH of the mucosal solution below pH 5 reversibly causes decreased current-generating capability of the tissue. Pretreatment of the tissue with amiloride abolishes this pH effect. The implication is that the low pH affects the Na+-entry step into cells. \"Titration curves\" of current vs. pH had an apparent pK approximately 4.0. Ouabain and K+-free solutions both cause decreases in active Na+ and Cl- current. Calculations indicate that a shunt may account for only a small (less than 30%) percentage of total transepithelial conductance."}
{"id": "PMID:24347", "title": "Norepinephrine: hormone and neurotransmitter in man.", "content": "To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function.", "contents": "Norepinephrine: hormone and neurotransmitter in man. To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function."}
{"id": "PMID:24348", "title": "Acetazolamide and renal ammoniagenesis.", "content": "The effect of acetazolamide on ammonia-producing enzyme systems was determined in vitro at concentrations comparable to those which have been shown to abolish ammonium excretion in vivo. No change in the activity of glutaminase or gamma-glutamyl transpeptidase could be observed at concentrations up to 0.2 mM acetazolamide, and concentrations up to 1 mM were without effect on D-glutamyltransferase activity. Therefore, the effect of acetazolamide to abolish ammonium excretion cannot be explained by an action of the drug to inhibit ammoniagenesis.", "contents": "Acetazolamide and renal ammoniagenesis. The effect of acetazolamide on ammonia-producing enzyme systems was determined in vitro at concentrations comparable to those which have been shown to abolish ammonium excretion in vivo. No change in the activity of glutaminase or gamma-glutamyl transpeptidase could be observed at concentrations up to 0.2 mM acetazolamide, and concentrations up to 1 mM were without effect on D-glutamyltransferase activity. Therefore, the effect of acetazolamide to abolish ammonium excretion cannot be explained by an action of the drug to inhibit ammoniagenesis."}
{"id": "PMID:24349", "title": "Cerebral blood flow in birds: effect of hypoxia.", "content": "The effect of hypoxia on cerebral blood flow in ducks was investigated by the rate at which arterially injected xenon-133 was cleared from the duck's brain. A two-component clearance curve resulted, which we have attributed to flow through the grey and white matter. Decreasing the arterial oxygen tension (PaO2) to 75 mmHg had no effect on cerebral blood flow. However, decreasing the PaO2 below 75 mmHg significantly increased blood flow to the fast-clearing compartment. The greatest increase in blood flow was seen when the arterial PO2 was below 50 mmHg. At an arterial PO2 of 30 mmHg, the cerebral blood flow to the fast-clearing compartment was increased more than 600% above the normoxic level. The magnitude of this increase is much greater in the duck than has been reported for mammals at roughly equivalent arterial oxygen tensions. The ability of avian cerebral blood flow to increase at moderate levels of hypoxia, plus the magnitude of the increase, may play a role in the exceptional tolerance of birds to hypoxia.", "contents": "Cerebral blood flow in birds: effect of hypoxia. The effect of hypoxia on cerebral blood flow in ducks was investigated by the rate at which arterially injected xenon-133 was cleared from the duck's brain. A two-component clearance curve resulted, which we have attributed to flow through the grey and white matter. Decreasing the arterial oxygen tension (PaO2) to 75 mmHg had no effect on cerebral blood flow. However, decreasing the PaO2 below 75 mmHg significantly increased blood flow to the fast-clearing compartment. The greatest increase in blood flow was seen when the arterial PO2 was below 50 mmHg. At an arterial PO2 of 30 mmHg, the cerebral blood flow to the fast-clearing compartment was increased more than 600% above the normoxic level. The magnitude of this increase is much greater in the duck than has been reported for mammals at roughly equivalent arterial oxygen tensions. The ability of avian cerebral blood flow to increase at moderate levels of hypoxia, plus the magnitude of the increase, may play a role in the exceptional tolerance of birds to hypoxia."}
{"id": "PMID:24350", "title": "Altered hemodynamic responses to acute hypoxemia in spontaneously hypertensive rats.", "content": "Conscious spontaneously hypertensive rats (SHR), 5--7 wk old, were studied hemodynamically by the direct Fick procedure to determine whether high total peripheral resistance (TPR) coexisted with increased oxygen consumption (QO2) at an early stage of hypertension development. Since under resting conditions cardiac output in SHR was not significantly different from normotensive controls, the elevated arterial pressure and QO2 were associated with increased TPR. Arterial hypoxemia was induced to reduce oxygen availability and to assess whether increased TPR in SHR could be reversed by this procedure. During hypoxemia, normotensive controls (WKY) responded with increased cardiac output and decreased arterial pressure and TPR. In contrast, arterial pressure and cardiac output fell in SHR; and the increased TPR persisted. QO2 fell in hypoxemic SHR demonstrating that the relationship between total body oxygen consumption and cardiac output was abnormal in young SHR, and that increased TPR in SHR was not dependent on resting levels of QO2 or oxygen availability. Although QO2 was elevated in SHR compared to age-matched WKY, this condition was not essential for maintained elevated vascular resistance.", "contents": "Altered hemodynamic responses to acute hypoxemia in spontaneously hypertensive rats. Conscious spontaneously hypertensive rats (SHR), 5--7 wk old, were studied hemodynamically by the direct Fick procedure to determine whether high total peripheral resistance (TPR) coexisted with increased oxygen consumption (QO2) at an early stage of hypertension development. Since under resting conditions cardiac output in SHR was not significantly different from normotensive controls, the elevated arterial pressure and QO2 were associated with increased TPR. Arterial hypoxemia was induced to reduce oxygen availability and to assess whether increased TPR in SHR could be reversed by this procedure. During hypoxemia, normotensive controls (WKY) responded with increased cardiac output and decreased arterial pressure and TPR. In contrast, arterial pressure and cardiac output fell in SHR; and the increased TPR persisted. QO2 fell in hypoxemic SHR demonstrating that the relationship between total body oxygen consumption and cardiac output was abnormal in young SHR, and that increased TPR in SHR was not dependent on resting levels of QO2 or oxygen availability. Although QO2 was elevated in SHR compared to age-matched WKY, this condition was not essential for maintained elevated vascular resistance."}
{"id": "PMID:24351", "title": "Controlling the highest lactate dehydrogenase activity known in nature.", "content": "In the shipjack, Euthynnus pelamis, white muscle appears to possess a powerful anaerobic capacity as well as a significant carbohydrate based aerobic potential. Lactate dehydrogenase occurs at higher activities than found thus far anywhere else in nature and clearly functions in anaerobic glycolysis. Alpha-glycerophosphate dehydrogenase also occurs in unusually high activities and appears to play a role in aerobic glycolysis. Regulation of these two reactions is accomplished by temperature, pH, and creatine phosphate levels. High temperature, low pH, and low creatine phosphate levels all appear to favor lactate dehydrogenase over alpha-glycerophosphate dehydrogenase; low temperature, high pH, and high creatine-phosphate levels, all expected during the quiescent state in this species, and when metabolism in aerobic, all favor alpha-glycerophosphate dehydrogenase activity.", "contents": "Controlling the highest lactate dehydrogenase activity known in nature. In the shipjack, Euthynnus pelamis, white muscle appears to possess a powerful anaerobic capacity as well as a significant carbohydrate based aerobic potential. Lactate dehydrogenase occurs at higher activities than found thus far anywhere else in nature and clearly functions in anaerobic glycolysis. Alpha-glycerophosphate dehydrogenase also occurs in unusually high activities and appears to play a role in aerobic glycolysis. Regulation of these two reactions is accomplished by temperature, pH, and creatine phosphate levels. High temperature, low pH, and low creatine phosphate levels all appear to favor lactate dehydrogenase over alpha-glycerophosphate dehydrogenase; low temperature, high pH, and high creatine-phosphate levels, all expected during the quiescent state in this species, and when metabolism in aerobic, all favor alpha-glycerophosphate dehydrogenase activity."}
{"id": "PMID:24353", "title": "Gastric mucosal defense mechanisms: effects of salicylate and histamine.", "content": "Some of the recent concepts about the gastric mucosal defense mechanisms against damage by luminal acid and the effects of histamine and salicylate on these mechanisms are reviewed. The mucosal barrier to acid appears to consist of at least two physiologic components: a permeability mechanism and a metabolic mechanism related to cellular bicarbonate production as a result of acid secretion. In the absence of salicylate, histamine appears to exert some protection by affecting both mechanisms, but in the presence of salicylate, histamine's protective effect is limited to altering mucosal permeability. The actions of salicylate on the gastric mucosa are complex, related in part to the concentration of salicylate and the pH of the luminal fluid. The damaging effects of salicylate appear to be related more to the concentration of acid in the lumen than to the lipid solubility of the drug. Salicylate increases permeability regardless of pH; the increase is initially selective for cations and subsequently becomes nonselective, involving both cations and anions. Although both low and high concentrations of salicylate increase mucosal permeability to hydrogen ions, only high concentrations of salicylate affect cellular bicarbonate production.", "contents": "Gastric mucosal defense mechanisms: effects of salicylate and histamine. Some of the recent concepts about the gastric mucosal defense mechanisms against damage by luminal acid and the effects of histamine and salicylate on these mechanisms are reviewed. The mucosal barrier to acid appears to consist of at least two physiologic components: a permeability mechanism and a metabolic mechanism related to cellular bicarbonate production as a result of acid secretion. In the absence of salicylate, histamine appears to exert some protection by affecting both mechanisms, but in the presence of salicylate, histamine's protective effect is limited to altering mucosal permeability. The actions of salicylate on the gastric mucosa are complex, related in part to the concentration of salicylate and the pH of the luminal fluid. The damaging effects of salicylate appear to be related more to the concentration of acid in the lumen than to the lipid solubility of the drug. Salicylate increases permeability regardless of pH; the increase is initially selective for cations and subsequently becomes nonselective, involving both cations and anions. Although both low and high concentrations of salicylate increase mucosal permeability to hydrogen ions, only high concentrations of salicylate affect cellular bicarbonate production."}
{"id": "PMID:24354", "title": "The neurohumoral response to trauma.", "content": "The bodily response to injury is an integrated and protective mechanism involving all systems, and hence it should be considered as a whole. The nervous system, especially the psychic center of the cerebral cortex, seems to initiate these responses. In the present study the neurohumoral response to trauma was assessed in experimental animals and clinical subjects. Immediately after trauma acetylcholine levels increased, suggesting enhanced activity of the central nervous system. This was followed by predominant activity of the sympathetic nervous system, as evidenced by increased catecholamine levels. During the later postoperative period, histamine levels also increased. There appears to be a good correlation between increased histamine content and fibroblastic proliferation in the traumatized area. These observations suggest that levels of the neurohumors increase in a definite sequence after trauma, facilitating the process of repair, regeneration, and normal convalescence. Therefore, trauma should be minimized during repair and the patient should receive proper sedation and rest during the pre- and postoperative periods, since each quantum of response depends upon the amount of sensory input that occurs at the time of trauma and in the post-traumatic period.", "contents": "The neurohumoral response to trauma. The bodily response to injury is an integrated and protective mechanism involving all systems, and hence it should be considered as a whole. The nervous system, especially the psychic center of the cerebral cortex, seems to initiate these responses. In the present study the neurohumoral response to trauma was assessed in experimental animals and clinical subjects. Immediately after trauma acetylcholine levels increased, suggesting enhanced activity of the central nervous system. This was followed by predominant activity of the sympathetic nervous system, as evidenced by increased catecholamine levels. During the later postoperative period, histamine levels also increased. There appears to be a good correlation between increased histamine content and fibroblastic proliferation in the traumatized area. These observations suggest that levels of the neurohumors increase in a definite sequence after trauma, facilitating the process of repair, regeneration, and normal convalescence. Therefore, trauma should be minimized during repair and the patient should receive proper sedation and rest during the pre- and postoperative periods, since each quantum of response depends upon the amount of sensory input that occurs at the time of trauma and in the post-traumatic period."}
{"id": "PMID:24356", "title": "[Comparative investigations concerning the influence of pilocarpine and aceclidine on the glucose consumption of surviving ocular tissues (author's transl)].", "content": "Conservative glaucoma therapy repeated during a whole lifetime raises the question of medicamentuous tolerance. Recently, cultivation of normal lens epithelia and of iris tissue has made possible determination of metabolic functions with and without application of different medicaments. Preceding experiments revealed a diminution in glucose consumption by these tissues after addition of pilocarpine. Comparative studies show 0.25 g/100 ml medium to be maximum concentration of aceclidine allowing cellular survival. With this dilution, the glucose metabolism of lens epithelia was much more sensitive to aceclidine than to pilocarpine. This was less true for iris tissue. Accordingly, the lens of an aceclidine-treated patient requires careful observation.", "contents": "[Comparative investigations concerning the influence of pilocarpine and aceclidine on the glucose consumption of surviving ocular tissues (author's transl)]. Conservative glaucoma therapy repeated during a whole lifetime raises the question of medicamentuous tolerance. Recently, cultivation of normal lens epithelia and of iris tissue has made possible determination of metabolic functions with and without application of different medicaments. Preceding experiments revealed a diminution in glucose consumption by these tissues after addition of pilocarpine. Comparative studies show 0.25 g/100 ml medium to be maximum concentration of aceclidine allowing cellular survival. With this dilution, the glucose metabolism of lens epithelia was much more sensitive to aceclidine than to pilocarpine. This was less true for iris tissue. Accordingly, the lens of an aceclidine-treated patient requires careful observation."}
{"id": "PMID:24357", "title": "Plasma lorazepam levels. A study following single dose administration of 2 and 4 mg by different routes.", "content": "Plasma lorazepam levels were studied following single doses of 2 mg and 4 mg in patients and volunteers. There was a slightly more rapid uptake of drug following deep intramuscular injection than when taken by mouth. Plasma levels declined rapidly following intravenous injection (t1/2 of approximately 2-3 hours). Two hours after giving the drug the plasma levels were similar irrespective of the route of administration. The second phase decline was very slow and one third of the peak concentration was still in the blood at 24 hours.", "contents": "Plasma lorazepam levels. A study following single dose administration of 2 and 4 mg by different routes. Plasma lorazepam levels were studied following single doses of 2 mg and 4 mg in patients and volunteers. There was a slightly more rapid uptake of drug following deep intramuscular injection than when taken by mouth. Plasma levels declined rapidly following intravenous injection (t1/2 of approximately 2-3 hours). Two hours after giving the drug the plasma levels were similar irrespective of the route of administration. The second phase decline was very slow and one third of the peak concentration was still in the blood at 24 hours."}
{"id": "PMID:24376", "title": "[Metabolism of glucides and polyols and disorders of their utilization].", "content": "The first part of this report is devoted to a description of the metabolic pathways of the principle carbohydrates and polyols. The second part is concerned with the utilisation of these energy-providing substrates, when used in parenteral alimentation. Notions emerge of \"total clearance\" and of coefficient of utilisation in relation to the rate of administration for each of them. Finally, the third part deals with disturbances of carbolydate and polyol metabolism during stress and diabetes and the possiblilities of the development of hyperlactatemia according to the substances used or the pathological circumstances encountered. A table attempts to summarise the potential complications in comparison with all the substrates used in parenteral alimentation.", "contents": "[Metabolism of glucides and polyols and disorders of their utilization]. The first part of this report is devoted to a description of the metabolic pathways of the principle carbohydrates and polyols. The second part is concerned with the utilisation of these energy-providing substrates, when used in parenteral alimentation. Notions emerge of \"total clearance\" and of coefficient of utilisation in relation to the rate of administration for each of them. Finally, the third part deals with disturbances of carbolydate and polyol metabolism during stress and diabetes and the possiblilities of the development of hyperlactatemia according to the substances used or the pathological circumstances encountered. A table attempts to summarise the potential complications in comparison with all the substrates used in parenteral alimentation."}
{"id": "PMID:24377", "title": "[Glucide intolerance and its pathogenic mechanisms during parenteral feeding].", "content": "Hyperglycaemia during parenteral alimentation occurs either as a result of an error in the supplies provided or as a result of diminished carbohydrate tolerance. The circumstances surrounding the development of carbohydrate intolerance are essentially : severe infections, major catabolic states, renal insufficiency, extensive burns, pancreatic problems and diabetes. From a pathogenic standpoint, there are two dominant elements : disturbances in hepatic gluconeogenesis and changes in insulin secretion and in resistance to insulin. The physiopathology is dominated by the risk of hyperosmolarity. Hypoglycaemia occurs most frequently as the result of a manit fest error : too sudded interruption of carbohydrate supplies or two high dosage of exogenous insulin.", "contents": "[Glucide intolerance and its pathogenic mechanisms during parenteral feeding]. Hyperglycaemia during parenteral alimentation occurs either as a result of an error in the supplies provided or as a result of diminished carbohydrate tolerance. The circumstances surrounding the development of carbohydrate intolerance are essentially : severe infections, major catabolic states, renal insufficiency, extensive burns, pancreatic problems and diabetes. From a pathogenic standpoint, there are two dominant elements : disturbances in hepatic gluconeogenesis and changes in insulin secretion and in resistance to insulin. The physiopathology is dominated by the risk of hyperosmolarity. Hypoglycaemia occurs most frequently as the result of a manit fest error : too sudded interruption of carbohydrate supplies or two high dosage of exogenous insulin."}
{"id": "PMID:24375", "title": "Neonatal gastric pH.", "content": "The pH of gastric juice, obtained 3 to 4 minutes after birth in 158 unselected neonates, varied between 7.5 and 8.5 in 8 meconium-containing specimens and ranged from 1.4 to 7.8 in 150 meconium-free samples. In mature infants of the latter group, pH was (1) significantly lower after vaginal delivery than after cesarean section; (2) tended to be lower after section preceded by labor than after elective section; and (3) was lowest after precipitate delivery. In premature infants, pH was above 7 regardless of mode of delivery. Three was no correlation between neonatal gastric pH and pH of simultaneously obtained maternal gastric juice, pH of amniotic fluid, pH of cord blood duration of rupture of membranes, birth weight, or Apgar score. It was concluded that the mature human fetus produces gastric acidity in response to stresses associated with labor and vaginal delivery. The possibility of a low gastric pH and the resultant pulmonary damage if aspirated must be considered in the initial care of thew newborn with poor muscle tone or reflex activity as well as in the anesthetic management of neonates undergoing emergency surgery.", "contents": "Neonatal gastric pH. The pH of gastric juice, obtained 3 to 4 minutes after birth in 158 unselected neonates, varied between 7.5 and 8.5 in 8 meconium-containing specimens and ranged from 1.4 to 7.8 in 150 meconium-free samples. In mature infants of the latter group, pH was (1) significantly lower after vaginal delivery than after cesarean section; (2) tended to be lower after section preceded by labor than after elective section; and (3) was lowest after precipitate delivery. In premature infants, pH was above 7 regardless of mode of delivery. Three was no correlation between neonatal gastric pH and pH of simultaneously obtained maternal gastric juice, pH of amniotic fluid, pH of cord blood duration of rupture of membranes, birth weight, or Apgar score. It was concluded that the mature human fetus produces gastric acidity in response to stresses associated with labor and vaginal delivery. The possibility of a low gastric pH and the resultant pulmonary damage if aspirated must be considered in the initial care of thew newborn with poor muscle tone or reflex activity as well as in the anesthetic management of neonates undergoing emergency surgery."}
{"id": "PMID:24380", "title": "[Circulating lipids in prolonged postoperative parenteral feeding: their changes depending on the nature of energy intake].", "content": "Repeated estimations of circulating total lipids and various fractions were made during the postoperative period in patients receiving parenteral nutrition for more than ten days. The patients were paired in relation to the underlying pathology and divided into two group : the first receiving energy supplements in the form of carbohydrates alone, whilst the second received part of this supply in the form of lipid emulsions (Trive 1000).  Total lipids and various plasma fractions, with the exception of free fatty acids, increased progressively during the postoperative period, regardless of the inital values and independently of the lipid content of the nutrition fluids given. There was no significant difference between those patients who received lipid emulsions and those who did not. Free fatty acids remained at levels slightly greater than normal in the group which did not receive lipids. They were significantly higher in the group given lipid emulsions, though it was not possible to precisely define their orgin.", "contents": "[Circulating lipids in prolonged postoperative parenteral feeding: their changes depending on the nature of energy intake]. Repeated estimations of circulating total lipids and various fractions were made during the postoperative period in patients receiving parenteral nutrition for more than ten days. The patients were paired in relation to the underlying pathology and divided into two group : the first receiving energy supplements in the form of carbohydrates alone, whilst the second received part of this supply in the form of lipid emulsions (Trive 1000).  Total lipids and various plasma fractions, with the exception of free fatty acids, increased progressively during the postoperative period, regardless of the inital values and independently of the lipid content of the nutrition fluids given. There was no significant difference between those patients who received lipid emulsions and those who did not. Free fatty acids remained at levels slightly greater than normal in the group which did not receive lipids. They were significantly higher in the group given lipid emulsions, though it was not possible to precisely define their orgin."}
{"id": "PMID:24381", "title": "[Fat overload during intake of lipids].", "content": "A review of the recent literature indicates that fat overload during the infusion of lipid emulsions remains rare, at least clinically. Nevertheless, two pictures may be seen, the physiopathology of which is discussed:--overload syndrome, with an association essentially of general and digestive signs, related to the accumulation of lipids in a certain number of parenchymatous tissues;--fat embolism. Problem may be seen at any time after administration of the solution is begun. Youth seems to predominate amongst the favourising factors. Prevention is possible if rules of caution concerning dose and the rate of administration are respected, combined with biological surveillance involving at laboratory studies at least once a week.", "contents": "[Fat overload during intake of lipids]. A review of the recent literature indicates that fat overload during the infusion of lipid emulsions remains rare, at least clinically. Nevertheless, two pictures may be seen, the physiopathology of which is discussed:--overload syndrome, with an association essentially of general and digestive signs, related to the accumulation of lipids in a certain number of parenchymatous tissues;--fat embolism. Problem may be seen at any time after administration of the solution is begun. Youth seems to predominate amongst the favourising factors. Prevention is possible if rules of caution concerning dose and the rate of administration are respected, combined with biological surveillance involving at laboratory studies at least once a week."}
{"id": "PMID:24382", "title": "[Disorders of hemostasis during intake of lipids].", "content": "Lipid emulsions based upon soya triglycerides and widely used in parenteral nutrition. Haematological surveillance of the patients, and in particular the study of coagulation, shows slight changes in platelet adhesiveness and a transient hypercoagulability state proportional to the concentration of the lipid emulsion. Nevertheless, these findings must be interpreted with the greatest caution, inasmuch as the laboratory tests involved are technically delicate. The results obtained may be contradictory according to the protocol used. Finally, in patients receiving intensive therapy, there are multiple factors (stress, prolonge;d bedrest, hypercatabolism) which may alter coagulation quite independently of the prescription of lipids.", "contents": "[Disorders of hemostasis during intake of lipids]. Lipid emulsions based upon soya triglycerides and widely used in parenteral nutrition. Haematological surveillance of the patients, and in particular the study of coagulation, shows slight changes in platelet adhesiveness and a transient hypercoagulability state proportional to the concentration of the lipid emulsion. Nevertheless, these findings must be interpreted with the greatest caution, inasmuch as the laboratory tests involved are technically delicate. The results obtained may be contradictory according to the protocol used. Finally, in patients receiving intensive therapy, there are multiple factors (stress, prolonge;d bedrest, hypercatabolism) which may alter coagulation quite independently of the prescription of lipids."}
{"id": "PMID:24383", "title": "[Blood coagulation during prolonged postoperative parenteral feeding containing lipids].", "content": "Blood coagulation was studied in two groups of fifteen patients of the same type during parenteral nutrition lasting for more then ten days and given during the postoperative period. The first batch of patients, taken as a control group, received parenteral nutrition with carbohydrates and proteins, whilst the second group received lipids in addition. Study of blood coagulation, carried out every three days, involved : thromboelastogen on whole blood and plasma, platelet count, platelet adhesiveness and the estimation of factors II, V, VII and X, fibrinogen, plasminogen and fibrinogen break-down products. In the patients not receiving lipids, the normal alterations seen during the postoperative period occurred : normalisation in plasminogen levels and in F.B.P., and an increase in the number of platelets and in fibrinogen level. The presence of lipids in the nutritional fluids resulted in changes in the same direction, but the increase in platelet count was slighter and fibrinogen level, after a slight increase, returned to initial values on the 20th day of parenteral nutrition. Fibrinogen was the only factor which showed any significant difference between the two groups.", "contents": "[Blood coagulation during prolonged postoperative parenteral feeding containing lipids]. Blood coagulation was studied in two groups of fifteen patients of the same type during parenteral nutrition lasting for more then ten days and given during the postoperative period. The first batch of patients, taken as a control group, received parenteral nutrition with carbohydrates and proteins, whilst the second group received lipids in addition. Study of blood coagulation, carried out every three days, involved : thromboelastogen on whole blood and plasma, platelet count, platelet adhesiveness and the estimation of factors II, V, VII and X, fibrinogen, plasminogen and fibrinogen break-down products. In the patients not receiving lipids, the normal alterations seen during the postoperative period occurred : normalisation in plasminogen levels and in F.B.P., and an increase in the number of platelets and in fibrinogen level. The presence of lipids in the nutritional fluids resulted in changes in the same direction, but the increase in platelet count was slighter and fibrinogen level, after a slight increase, returned to initial values on the 20th day of parenteral nutrition. Fibrinogen was the only factor which showed any significant difference between the two groups."}
{"id": "PMID:24384", "title": "[Cholestatic icterus during parenteral feeding in the newborn ano infants].", "content": "The authors observed six cases of cholestatis jaundice occuring during parenteral alimentation in the newborn and the infant. In 4 cases, local factors (duodenal atresia, necrosing enteritis of prematurity) or general factors (mucoviscidosis) probably played an essential role. In two cases, the parenteral alimentation seemed to be a main factor, but in one case with excessive and imbalanced supplies of amino acids. Three patients survived, with regression of the jaundice in 15 days to three weeks following the interruption of parenteral alimentation.", "contents": "[Cholestatic icterus during parenteral feeding in the newborn ano infants]. The authors observed six cases of cholestatis jaundice occuring during parenteral alimentation in the newborn and the infant. In 4 cases, local factors (duodenal atresia, necrosing enteritis of prematurity) or general factors (mucoviscidosis) probably played an essential role. In two cases, the parenteral alimentation seemed to be a main factor, but in one case with excessive and imbalanced supplies of amino acids. Three patients survived, with regression of the jaundice in 15 days to three weeks following the interruption of parenteral alimentation."}
{"id": "PMID:24385", "title": "[Prevention of metabolic complications in prolonged parenteral feeding].", "content": "Modern technics in parenteral nutrition can prevent metabolic and infectious complications. Supplying a patient with a daily ration according to his needs in the form of either hyper or normo-nutrition serves as the basis for this prevention. All that is required for success is a deep venous approach and regular biological and clinical surveillance of the patient. The authors conclusions are based on a study of 1.800 patients.", "contents": "[Prevention of metabolic complications in prolonged parenteral feeding]. Modern technics in parenteral nutrition can prevent metabolic and infectious complications. Supplying a patient with a daily ration according to his needs in the form of either hyper or normo-nutrition serves as the basis for this prevention. All that is required for success is a deep venous approach and regular biological and clinical surveillance of the patient. The authors conclusions are based on a study of 1.800 patients."}
{"id": "PMID:24386", "title": "[Metabolic disorders in experimental hepatic insufficiency and parenteral feeding].", "content": "Anhepatia is a complete experimental model for the study of metabolic disturbances associated with hepatic insufficiency. The authors report their experience based upon 16 cases of total hepatectomy in the dog. The animals received different types of hepatic assistance : group 1 (2 dogs), carbohydrate assistance (glucose 7 g/kg/24 h) ; group II (2 dogs), carbohydrate and haemostatic assistance : homologous plasma 50 ml/kg body weight per 24 hours previously stored at - 80 degrees C ; group III (2 dogs) same nutrition as in group II, combined with amino acids : leucine 53, 3 mg, isoleucine 46, 6 mg ; valine 53,3 mg alpha-ketonic acid (lg/kg/24 h) ; group IV (10 dogs, same nutrition as in group III, combined with supplements in neuro transmitter precursors : 6 dopa 1,66 mg, 5 hydroxy-tryptophane 2 mg and choline 16, 66 mg/kg/24h. Metabolic disturbances and their course were analysed in detail. Results : (mean survival) - group I : 24 +/- 4 hours; group II : 36 +/- 9 hours; group III : 42 +/- 4 hours; group IV : 90 +/- 9 hours. The average survival differed significantly for groups III and IV (p less than 0,01) in comparison with control groups I and II. The replacement of essential hepatic functions such as blood glucose regulation, coagulation, detoxication and the provision of neurotransmitter precursors made possible 4 days survival after total hepatectomy.", "contents": "[Metabolic disorders in experimental hepatic insufficiency and parenteral feeding]. Anhepatia is a complete experimental model for the study of metabolic disturbances associated with hepatic insufficiency. The authors report their experience based upon 16 cases of total hepatectomy in the dog. The animals received different types of hepatic assistance : group 1 (2 dogs), carbohydrate assistance (glucose 7 g/kg/24 h) ; group II (2 dogs), carbohydrate and haemostatic assistance : homologous plasma 50 ml/kg body weight per 24 hours previously stored at - 80 degrees C ; group III (2 dogs) same nutrition as in group II, combined with amino acids : leucine 53, 3 mg, isoleucine 46, 6 mg ; valine 53,3 mg alpha-ketonic acid (lg/kg/24 h) ; group IV (10 dogs, same nutrition as in group III, combined with supplements in neuro transmitter precursors : 6 dopa 1,66 mg, 5 hydroxy-tryptophane 2 mg and choline 16, 66 mg/kg/24h. Metabolic disturbances and their course were analysed in detail. Results : (mean survival) - group I : 24 +/- 4 hours; group II : 36 +/- 9 hours; group III : 42 +/- 4 hours; group IV : 90 +/- 9 hours. The average survival differed significantly for groups III and IV (p less than 0,01) in comparison with control groups I and II. The replacement of essential hepatic functions such as blood glucose regulation, coagulation, detoxication and the provision of neurotransmitter precursors made possible 4 days survival after total hepatectomy."}
{"id": "PMID:24387", "title": "[Three cases of coma during parenteral alimentation].", "content": "Three cases of coma occuring during parenteral alimentation are presented. The common factor was that they occurred during the phase of realimentation in patients with severely impaired nutrition. In two cases out of three, the coma marked the beginning of the absolute or relative anabolic period. They were studied clinically, biologically and electrically. In one case only, major hypophosphataemia was discovered (2mg/l). Of the three patients, one only died 4 days after the onset of coma, whilst clinical and biological characteristics had returned to normal.", "contents": "[Three cases of coma during parenteral alimentation]. Three cases of coma occuring during parenteral alimentation are presented. The common factor was that they occurred during the phase of realimentation in patients with severely impaired nutrition. In two cases out of three, the coma marked the beginning of the absolute or relative anabolic period. They were studied clinically, biologically and electrically. In one case only, major hypophosphataemia was discovered (2mg/l). Of the three patients, one only died 4 days after the onset of coma, whilst clinical and biological characteristics had returned to normal."}
{"id": "PMID:24388", "title": "[Deficiencies in trace elements during parenteral alimentation].", "content": "During recent years, techniques of parenteral alimentation have seen the development of complications due to deficiencies in trace elements. The main deficiency states described involve iron, copper and zinc. In addition to these three trace elements, mangan\u00e8se and cobalt are included in this study. The metabolism, physiological role, needs in parenteral alimentation and clinical and metabolic effects of possible deficiency are described for each of these elements.", "contents": "[Deficiencies in trace elements during parenteral alimentation]. During recent years, techniques of parenteral alimentation have seen the development of complications due to deficiencies in trace elements. The main deficiency states described involve iron, copper and zinc. In addition to these three trace elements, mangan\u00e8se and cobalt are included in this study. The metabolism, physiological role, needs in parenteral alimentation and clinical and metabolic effects of possible deficiency are described for each of these elements."}
{"id": "PMID:24389", "title": "[Routine comparison of trace element deficiencies during parenteral alimentation].", "content": "In 50 patients aged between 3 and 84 years treated in a multidisciplinary Intensive Care Unit and receiving parenteral alimentation, deficiency in certain trace elements or electrolytes (Cu++, Zn++, Mn++, Co++, PO-4, Mg++) was prevented or treated by the administration of a glucose solution (MB 147 G) enriched in trace elements. The aim of the present study was to demonstrate, on the basis of assay of serum levels of the trace elements involved, with the exception of Mn and Co, the effectiveness of treatment. Reference values were determined on the one hand in healthy individuals for normal figures and secondly on subjects included in the study, already on parenteral alimentation for several days, before treatment with MB 147 G, in order to demonstrate the existence of a deficiency (patient control values). In the case of PO--4, however, the patient control values concerned at one and the same time subjects in the study before treatment with MB 147 G and other patients receiving parenteral alimentation who were not part of the trial. MB 147 G solution was presented in units of 500 ml associated with glucose of varying concentrations (15 p. 100, 30 p. 100, 50 p. 100). The average daily amount administered, over a period of 236 days, was 3 unites per 24 hours, corresponding to an intake of copper of 3.78 mg, 3.90 mg of zinc, 0.20 mg of manganese, 0.24 mg of cobalt, 363 mg of magnesium, 240 mg of calcium and 15 mEz of phosphates. The results show that levels of copper, zinc, magnesium and phosphates were low during parenteral alimentation. The administration of MB 147 G resulted in a significant increase in these values, without there being any evidence of accumulation.", "contents": "[Routine comparison of trace element deficiencies during parenteral alimentation]. In 50 patients aged between 3 and 84 years treated in a multidisciplinary Intensive Care Unit and receiving parenteral alimentation, deficiency in certain trace elements or electrolytes (Cu++, Zn++, Mn++, Co++, PO-4, Mg++) was prevented or treated by the administration of a glucose solution (MB 147 G) enriched in trace elements. The aim of the present study was to demonstrate, on the basis of assay of serum levels of the trace elements involved, with the exception of Mn and Co, the effectiveness of treatment. Reference values were determined on the one hand in healthy individuals for normal figures and secondly on subjects included in the study, already on parenteral alimentation for several days, before treatment with MB 147 G, in order to demonstrate the existence of a deficiency (patient control values). In the case of PO--4, however, the patient control values concerned at one and the same time subjects in the study before treatment with MB 147 G and other patients receiving parenteral alimentation who were not part of the trial. MB 147 G solution was presented in units of 500 ml associated with glucose of varying concentrations (15 p. 100, 30 p. 100, 50 p. 100). The average daily amount administered, over a period of 236 days, was 3 unites per 24 hours, corresponding to an intake of copper of 3.78 mg, 3.90 mg of zinc, 0.20 mg of manganese, 0.24 mg of cobalt, 363 mg of magnesium, 240 mg of calcium and 15 mEz of phosphates. The results show that levels of copper, zinc, magnesium and phosphates were low during parenteral alimentation. The administration of MB 147 G resulted in a significant increase in these values, without there being any evidence of accumulation."}
{"id": "PMID:24390", "title": "[Hydrogen ion metabolism and parenteral alimentation].", "content": "The necessity of using solutions and emulsions in parenteral nutrition of solutions directly utilisable by the cell has led to the manufactur of substances with a composition and physico-chemical nature which greatly alters H+ ions balance. Theoretical calculation and various experimental protocois have shown that the production of H+ ions may be multiplied by 3 or 4. This explains the complications of metabolic acidosis seen in association with prolonged parenteral nutrition. There are two main sources : lipid emulsions and amino-acid solutions. One litre of lipid emulsion may provide 37 to 60 mEq of H+ ions. According to their formula, amino acid solutions may consume, or more often provide, large amounts of H+ ions (up to 20 mEq/gram of nitrogen). These physiopathological concepts should be taken into consideration in defining the compositions of fluids for parenteral nutrition, in particular when renal function is impaired.", "contents": "[Hydrogen ion metabolism and parenteral alimentation]. The necessity of using solutions and emulsions in parenteral nutrition of solutions directly utilisable by the cell has led to the manufactur of substances with a composition and physico-chemical nature which greatly alters H+ ions balance. Theoretical calculation and various experimental protocois have shown that the production of H+ ions may be multiplied by 3 or 4. This explains the complications of metabolic acidosis seen in association with prolonged parenteral nutrition. There are two main sources : lipid emulsions and amino-acid solutions. One litre of lipid emulsion may provide 37 to 60 mEq of H+ ions. According to their formula, amino acid solutions may consume, or more often provide, large amounts of H+ ions (up to 20 mEq/gram of nitrogen). These physiopathological concepts should be taken into consideration in defining the compositions of fluids for parenteral nutrition, in particular when renal function is impaired."}
{"id": "PMID:24391", "title": "[Metabolic problems associated with ethanol administration].", "content": "After reviewing the effects of ethanol on different metabolic processes, the author defines the doses of this alcohol which may be used in parenteral alimentation, its advantages and disadvantages. The latter in general outweigh the advantages and limit its use in parenteral nutrition.", "contents": "[Metabolic problems associated with ethanol administration]. After reviewing the effects of ethanol on different metabolic processes, the author defines the doses of this alcohol which may be used in parenteral alimentation, its advantages and disadvantages. The latter in general outweigh the advantages and limit its use in parenteral nutrition."}
{"id": "PMID:24392", "title": "[Inherited abnormalities in amino acid metabolism].", "content": "Inherited abnormalities in amino-acid metabolism, which up to a few years ago remained curiosities in the domain of the specialist, are now becoming almost of everyday significance. Improved knowledge, as a result of the combined efforts of paediatricians, genetecists and biochemists, has led to substantial progress, both clinically (diagnosis and treatment) as well as in the understanding of intermediary metabolisms and enzyme reactions. This \"jigsay puzzle\", the pieces of which fall gradually into place, has already resulted in spectacular results, the best example of which is that of phenylketonuria. In the past this disease inevitably led to increasing brain damage and has now become a purely biochemical disorder wince early diagnosis and appropriate diet enable the young infant to become a normal child and remain a healthy adult. These data are illustrated here.", "contents": "[Inherited abnormalities in amino acid metabolism]. Inherited abnormalities in amino-acid metabolism, which up to a few years ago remained curiosities in the domain of the specialist, are now becoming almost of everyday significance. Improved knowledge, as a result of the combined efforts of paediatricians, genetecists and biochemists, has led to substantial progress, both clinically (diagnosis and treatment) as well as in the understanding of intermediary metabolisms and enzyme reactions. This \"jigsay puzzle\", the pieces of which fall gradually into place, has already resulted in spectacular results, the best example of which is that of phenylketonuria. In the past this disease inevitably led to increasing brain damage and has now become a purely biochemical disorder wince early diagnosis and appropriate diet enable the young infant to become a normal child and remain a healthy adult. These data are illustrated here."}
{"id": "PMID:24393", "title": "[Biological and hormonal balance during oral nutrition, exclusive perenteral and mixed nutrition in children].", "content": "Exclusive parenteral nutrition and mixed feeding provided by the infusion of a solution of amino-acids, glucose and trace elements by a drip method, result in changes in biological and hormonal balance which have been compared with balance in the child on normal oral feeding. The 24-hour cortisol cycle tends to be attenuated. Blood glucose and, above all, blood insulin levels show major variations. Plasma free fatty acid levels, stable in exclusive parenteral nutrition, in general vary with mixed nutrition. On the basis of these findings, a constant flow should be ensured by use of a pump during exclusive parenteral nutrition. In mixed feeding, meals should be frequent and energy supplies given in the form of slowly absorbed carbohydrates.", "contents": "[Biological and hormonal balance during oral nutrition, exclusive perenteral and mixed nutrition in children]. Exclusive parenteral nutrition and mixed feeding provided by the infusion of a solution of amino-acids, glucose and trace elements by a drip method, result in changes in biological and hormonal balance which have been compared with balance in the child on normal oral feeding. The 24-hour cortisol cycle tends to be attenuated. Blood glucose and, above all, blood insulin levels show major variations. Plasma free fatty acid levels, stable in exclusive parenteral nutrition, in general vary with mixed nutrition. On the basis of these findings, a constant flow should be ensured by use of a pump during exclusive parenteral nutrition. In mixed feeding, meals should be frequent and energy supplies given in the form of slowly absorbed carbohydrates."}
{"id": "PMID:24394", "title": "[Clinical signs and etiological aspects of metabolic encephalopathies excluding liver encephalopathy and realimentation syndrome].", "content": "The clinical picture of metabolic encephalopathies has no aetiological specificity. It combines disturbances in conscious level dominated by disorientation and time and space and disturbances in motor activity, in particular tremor and asterixis. For each of the aetiologies studied, the following are considered: the circumstances of onset, the clinical and laboratory picture, the physiopathology and the treatment. From a diagnostic standpoint, particular emphasis should be placed upon the circumstances of onset which alone give any indication. The majority of these encephalopathies are caused by a lack of respect for simple rules in parenteral alimentation or by deficiencies. It is thus essentially an iatrogenic pathology. Treatment should be above all preventive.", "contents": "[Clinical signs and etiological aspects of metabolic encephalopathies excluding liver encephalopathy and realimentation syndrome]. The clinical picture of metabolic encephalopathies has no aetiological specificity. It combines disturbances in conscious level dominated by disorientation and time and space and disturbances in motor activity, in particular tremor and asterixis. For each of the aetiologies studied, the following are considered: the circumstances of onset, the clinical and laboratory picture, the physiopathology and the treatment. From a diagnostic standpoint, particular emphasis should be placed upon the circumstances of onset which alone give any indication. The majority of these encephalopathies are caused by a lack of respect for simple rules in parenteral alimentation or by deficiencies. It is thus essentially an iatrogenic pathology. Treatment should be above all preventive."}
{"id": "PMID:24395", "title": "[Amino acid disturbances in liver failure].", "content": "We have attempted to trace the development of the concept which stresses that the encephalopathy often seen with hepatic failure may be the result of derangement in amino acid metabolism in patients with failing livers. We have also proposed that the infusion of solutions which may normalize these plasma amino acids and decrease the amount of toxic aromatic amino acids within the circulation may help in the amelioration of the symptoms of hepatic encephalopathy. We believe that in our studies to date, the use of this solution has been a significant advantage in the care of these extremely ill patients. We would hope that when the solution becomes generally available, the provision of such solutions to such patients will result in the salvage of some lives lost at the present time because of hepatic failure and encephalopathy.", "contents": "[Amino acid disturbances in liver failure]. We have attempted to trace the development of the concept which stresses that the encephalopathy often seen with hepatic failure may be the result of derangement in amino acid metabolism in patients with failing livers. We have also proposed that the infusion of solutions which may normalize these plasma amino acids and decrease the amount of toxic aromatic amino acids within the circulation may help in the amelioration of the symptoms of hepatic encephalopathy. We believe that in our studies to date, the use of this solution has been a significant advantage in the care of these extremely ill patients. We would hope that when the solution becomes generally available, the provision of such solutions to such patients will result in the salvage of some lives lost at the present time because of hepatic failure and encephalopathy."}
{"id": "PMID:24397", "title": "[Comas of realimentation].", "content": "Parenteral realimentation in the patient with severely impaired nutrition is sometimes associated with the development of a metabolic encephalopathy with coma. The onset of this complication is sudden. The coma is deep, accompanied by signs of neuromuscular hyperexcitability and very marked hyperventilation. It generally regresses rapidly, without sequellae. The onset of such a realimentation coma should be feared in the presence of a certain combination of conditions : severely impaired nutrition, parenteral alimentation with a high level of nitrogen and calories, transfer to the anabolic phase (perfect carbohydrate utilisation, fall in blood phosphate levels with hypophosphaturia, sometimes very marked positivisation of nitrogen balance) and, sometimes, mild premonitory clinical signs. The relationship between this type of complication and hypophosphoraemia is quite definite, but the fall in serum phosphates would not appear to be directly responsible for the coma. The exact mechanism is not known. In order to avoid such complications, great caution should be observed in both the quality as well as the quantity of the intake, as well as in the clinical and laboratory surveillance of the malnourished patient undergoing realimentation.", "contents": "[Comas of realimentation]. Parenteral realimentation in the patient with severely impaired nutrition is sometimes associated with the development of a metabolic encephalopathy with coma. The onset of this complication is sudden. The coma is deep, accompanied by signs of neuromuscular hyperexcitability and very marked hyperventilation. It generally regresses rapidly, without sequellae. The onset of such a realimentation coma should be feared in the presence of a certain combination of conditions : severely impaired nutrition, parenteral alimentation with a high level of nitrogen and calories, transfer to the anabolic phase (perfect carbohydrate utilisation, fall in blood phosphate levels with hypophosphaturia, sometimes very marked positivisation of nitrogen balance) and, sometimes, mild premonitory clinical signs. The relationship between this type of complication and hypophosphoraemia is quite definite, but the fall in serum phosphates would not appear to be directly responsible for the coma. The exact mechanism is not known. In order to avoid such complications, great caution should be observed in both the quality as well as the quantity of the intake, as well as in the clinical and laboratory surveillance of the malnourished patient undergoing realimentation."}
{"id": "PMID:24398", "title": "[Electroencephalographic study of functional metabolic encephalopathies and comas during parenteral alimentation].", "content": "This review deals with the common E.E.G. characteristics of dysmetabolic encephalopathies and described the particular features of hepatic, respiratory and renal encephalopathies, as well as those resulting from a disturbance in carbohydrate, water and electrolyte metabolism. These now classical data are compared with the principal electroclinical appearances seen during parenteral alimentation : slow, ample wases, non-reactive, associated with a calm coma; overall depression of basal rhythm, with excessive myogram activity and corresponding to paroxysms of muscular hypertonia seen during the coma.", "contents": "[Electroencephalographic study of functional metabolic encephalopathies and comas during parenteral alimentation]. This review deals with the common E.E.G. characteristics of dysmetabolic encephalopathies and described the particular features of hepatic, respiratory and renal encephalopathies, as well as those resulting from a disturbance in carbohydrate, water and electrolyte metabolism. These now classical data are compared with the principal electroclinical appearances seen during parenteral alimentation : slow, ample wases, non-reactive, associated with a calm coma; overall depression of basal rhythm, with excessive myogram activity and corresponding to paroxysms of muscular hypertonia seen during the coma."}
{"id": "PMID:24399", "title": "Effect of aflatoxin on the humoral and cell-mediated immune systems of the chicken.", "content": "Chickens fed 2.5 microgram of aflatoxin/g of diet from 2 to 4 weeks of age or from hatching to 4 weeks were deficient in cell-mediated immunity, as measured at 4 weeks of age by the graft-versus-host reaction. Delayed-type hypersensitive skin reactions to tuberculin were also reduced in chickens given dietary aflatoxin from hatching to 7 weeks of age. Humoral immunity, as measured by the ability of 4-week-old chicks to produce natural agglutinins to rabbit red blood cells, was not significantly altered by dietary aflatoxin. A significant decrease in concentrations of serum immunoglobulins (Ig) IgG and IgA, but no IgM, however, did occur in chicks given dietary aflatoxin from hatching to 4 weeks or between 2 and 4 weeks of age. Aflatoxin consumption from 0 to 2 weeks of age produced no marked effect on either cell-mediated or humoral immunity in 4-week-old chicks.", "contents": "Effect of aflatoxin on the humoral and cell-mediated immune systems of the chicken. Chickens fed 2.5 microgram of aflatoxin/g of diet from 2 to 4 weeks of age or from hatching to 4 weeks were deficient in cell-mediated immunity, as measured at 4 weeks of age by the graft-versus-host reaction. Delayed-type hypersensitive skin reactions to tuberculin were also reduced in chickens given dietary aflatoxin from hatching to 7 weeks of age. Humoral immunity, as measured by the ability of 4-week-old chicks to produce natural agglutinins to rabbit red blood cells, was not significantly altered by dietary aflatoxin. A significant decrease in concentrations of serum immunoglobulins (Ig) IgG and IgA, but no IgM, however, did occur in chicks given dietary aflatoxin from hatching to 4 weeks or between 2 and 4 weeks of age. Aflatoxin consumption from 0 to 2 weeks of age produced no marked effect on either cell-mediated or humoral immunity in 4-week-old chicks."}
{"id": "PMID:24401", "title": "Less dialysis-induced morbidity and vascular instability with bicarbonate in dialysate.", "content": "We devised three protocols to test the postulate that increased morbidity during high-efficiency dialysis with large-surface-area units (LS) might be due in part to the increased flux of bicarbonate out and acetate into the patient inherent is LS dialysis. The first protocol showed that with LS-acetate dialysis there was a marked fall in plasma bicarbonate and Pco2 during the first 3 to 4 h, followed by a rapid rise in bicarbonate above normal and return to control in Pco2. With LS-bicarbonate dialysis, these oscillations were largely eliminated. A second double-blind protocol showed that central nervous system-type symptoms noted during and after LS-acetate dialysis were reduced significantly by switching to LS-bicarbonate dialysis. The third protocol showed that with LS-carbonate the tolerable rate of ultrafiltration could be increased 67% compared with LS-acetate dialysis.", "contents": "Less dialysis-induced morbidity and vascular instability with bicarbonate in dialysate. We devised three protocols to test the postulate that increased morbidity during high-efficiency dialysis with large-surface-area units (LS) might be due in part to the increased flux of bicarbonate out and acetate into the patient inherent is LS dialysis. The first protocol showed that with LS-acetate dialysis there was a marked fall in plasma bicarbonate and Pco2 during the first 3 to 4 h, followed by a rapid rise in bicarbonate above normal and return to control in Pco2. With LS-bicarbonate dialysis, these oscillations were largely eliminated. A second double-blind protocol showed that central nervous system-type symptoms noted during and after LS-acetate dialysis were reduced significantly by switching to LS-bicarbonate dialysis. The third protocol showed that with LS-carbonate the tolerable rate of ultrafiltration could be increased 67% compared with LS-acetate dialysis."}
{"id": "PMID:24402", "title": "Metabolic acidosis after hyperalimentation with casein hydrolysate. Occurrence in a starved patient.", "content": "A 29-year-old woman with short bowel syndrome and prolonged starvation developed hyperchloremic metabolic acidosis after initiation of hyoeralimentation with a casein hydrolysate solution. The acidosis was not due to bicarbonate loss but was associated with diminished ability of the kidney to increase urinary acid excretion, particularly titratable acidity. Supplemental parenteral bicarbonate administration was necessary for two weeks until urinary acid excretion rose to normal.", "contents": "Metabolic acidosis after hyperalimentation with casein hydrolysate. Occurrence in a starved patient. A 29-year-old woman with short bowel syndrome and prolonged starvation developed hyperchloremic metabolic acidosis after initiation of hyoeralimentation with a casein hydrolysate solution. The acidosis was not due to bicarbonate loss but was associated with diminished ability of the kidney to increase urinary acid excretion, particularly titratable acidity. Supplemental parenteral bicarbonate administration was necessary for two weeks until urinary acid excretion rose to normal."}
{"id": "PMID:24403", "title": "Costs of educating child health associates.", "content": "Child health associates can be fully prepared to competently diagnose and treat 90% of ambulatory pediatric patients five years after completion of high school at a cost of approximately one-fourth the expense of educating a pediatrician to perform the same tasks and functions. A rational health planning policy should include the extensive utilization of child health associates as primary health care providers for children.", "contents": "Costs of educating child health associates. Child health associates can be fully prepared to competently diagnose and treat 90% of ambulatory pediatric patients five years after completion of high school at a cost of approximately one-fourth the expense of educating a pediatrician to perform the same tasks and functions. A rational health planning policy should include the extensive utilization of child health associates as primary health care providers for children."}
{"id": "PMID:24405", "title": "A chemiluminescent effect encountered in the liquid scintillation counting of 32P phosphate.", "content": "During the course of a kinetic enzyme study of bisphosphoglyceromutase (EC 2.7.5.4.) a chemiluminescent effect was encountered in the liquid scintillation counting of the beta-emission from 32Pi. A method is described for overcoming the effect, thereby permitting the accurate determination of the radioactive compounds. It is important to check for chemiluminescent effects early in the development of new procedures that involve liquid scintillation counting.", "contents": "A chemiluminescent effect encountered in the liquid scintillation counting of 32P phosphate. During the course of a kinetic enzyme study of bisphosphoglyceromutase (EC 2.7.5.4.) a chemiluminescent effect was encountered in the liquid scintillation counting of the beta-emission from 32Pi. A method is described for overcoming the effect, thereby permitting the accurate determination of the radioactive compounds. It is important to check for chemiluminescent effects early in the development of new procedures that involve liquid scintillation counting."}
{"id": "PMID:24406", "title": "The origin of the acidosis in hyperlactataemia.", "content": "Anaerobic glycolysis produces lactate, ATP, and water but there is no net change in the number of hydrogen ions: it does not produce lactic acid. The acidosis usually associated with hyperlactataemia is caused by hydrolysis of the ATP, with release of hydrogen ions. By contrast, ATP turnover by aerobic mechanisms is not acidifying because the released hydrogen ion is reutilised as more ATP is formed. Gluconeogenesis from lactate does not utilise hydrogen ions directly--in fact, it produces them. The associated net H+ utilisation is caused by the aerobic generation of the ATP and GTP required to drive glycolysis in reverse. It is suggested that only by understanding these important biochemical facts can the clinician found his diagnosis and treatment on a firm, rational basis.", "contents": "The origin of the acidosis in hyperlactataemia. Anaerobic glycolysis produces lactate, ATP, and water but there is no net change in the number of hydrogen ions: it does not produce lactic acid. The acidosis usually associated with hyperlactataemia is caused by hydrolysis of the ATP, with release of hydrogen ions. By contrast, ATP turnover by aerobic mechanisms is not acidifying because the released hydrogen ion is reutilised as more ATP is formed. Gluconeogenesis from lactate does not utilise hydrogen ions directly--in fact, it produces them. The associated net H+ utilisation is caused by the aerobic generation of the ATP and GTP required to drive glycolysis in reverse. It is suggested that only by understanding these important biochemical facts can the clinician found his diagnosis and treatment on a firm, rational basis."}
{"id": "PMID:24408", "title": "[Study of E. coli penicillin amidase. The pH dependence of the equilibrium constant of ampicillin enzymatic hydrolysis].", "content": "The equilibrium parameters of the hydrolysis of ampicillin catalysed by penicillin amidase were determined within the pH range of 4.5 to 5.5. The values of the ionization constants of the carboxy group of D-(-)-ALPHA-AMINOPHENYLACETIC ACID (PK1=1.80) and amino group of 6-aminopenicillanic acid (pK2=4.60) were estimated and pH-dependence of the effective free energy of ampicillin hydrolysis was calculated. It was shown that the thermodynamic optimum of ampicillin synthesis was at 3.20 (the value of the effective free energy under the experimental conditions was 3.27 kcal/mole). The value of the \"true\", pH-independent free energy of hydrolysis (deltasigma) of the amide bond in the ampicillin molecule was determined to be equal to 9.72 kcal/mole. The thermodynamic parameters of ampicillin and benzylpenicillin hydrolysis were compared. The amino group in the alpha-position of phenylacetic acid was shown to have a significant effect on the values of \"true\" free energy of hydrolysis of the penicillin amide bond and free ionization energy in the system.", "contents": "[Study of E. coli penicillin amidase. The pH dependence of the equilibrium constant of ampicillin enzymatic hydrolysis]. The equilibrium parameters of the hydrolysis of ampicillin catalysed by penicillin amidase were determined within the pH range of 4.5 to 5.5. The values of the ionization constants of the carboxy group of D-(-)-ALPHA-AMINOPHENYLACETIC ACID (PK1=1.80) and amino group of 6-aminopenicillanic acid (pK2=4.60) were estimated and pH-dependence of the effective free energy of ampicillin hydrolysis was calculated. It was shown that the thermodynamic optimum of ampicillin synthesis was at 3.20 (the value of the effective free energy under the experimental conditions was 3.27 kcal/mole). The value of the \"true\", pH-independent free energy of hydrolysis (deltasigma) of the amide bond in the ampicillin molecule was determined to be equal to 9.72 kcal/mole. The thermodynamic parameters of ampicillin and benzylpenicillin hydrolysis were compared. The amino group in the alpha-position of phenylacetic acid was shown to have a significant effect on the values of \"true\" free energy of hydrolysis of the penicillin amide bond and free ionization energy in the system."}
{"id": "PMID:24409", "title": "[Use of the penicillanic acid formation reaction for the analysis of penicillins. The quantitative determination of oxacillin].", "content": "A procedure for quantitative determination of oxacillin by means of spectrophotometry is described. The procedure is based on the capacity of penicillins to transform on heating in acid buffer solutions containing copper ions into respective penicillenic acids having specific absorption characteristics in the UV-spectrum region. The amount of oxacillin was estimated by the optical density of the solutions at a wave length of 335 nm corresponding to the absorption maximum of the penicillenic acid of oxacillin. The optimal conditions for the reaction of the penicillenic acid formation, i.e. pH of the buffer solution and the level of the copper ions in it, time and temperature of heating were determined. The data on the comparison of the specificity and reproducibility of the new method with the currently used ones for determination of oxacillin are presented.", "contents": "[Use of the penicillanic acid formation reaction for the analysis of penicillins. The quantitative determination of oxacillin]. A procedure for quantitative determination of oxacillin by means of spectrophotometry is described. The procedure is based on the capacity of penicillins to transform on heating in acid buffer solutions containing copper ions into respective penicillenic acids having specific absorption characteristics in the UV-spectrum region. The amount of oxacillin was estimated by the optical density of the solutions at a wave length of 335 nm corresponding to the absorption maximum of the penicillenic acid of oxacillin. The optimal conditions for the reaction of the penicillenic acid formation, i.e. pH of the buffer solution and the level of the copper ions in it, time and temperature of heating were determined. The data on the comparison of the specificity and reproducibility of the new method with the currently used ones for determination of oxacillin are presented."}
{"id": "PMID:24410", "title": "Stability and blood level determinations of cefaclor, a new oral cephalosporin antibiotic.", "content": "Cefaclor solutions in pH 2.5 and 4.5 buffers contained at least 90% of their initial activity after 72 h at 4 degrees C. Samples in pH 6.0, 7.0, and 8.0 buffers contained 70, 46, and 34%, respectively, of their initial activity after 72 h at 4 degrees C. After 72 h at 25 degrees C, samples prepared with pH 2.5, 4.5, 6.0, 7.0, and 8.0 buffers contained 95, 69, 16, 5, and 3%, respectively, of their initial activity. After 72 h at 37 degrees C, cefaclor solutions in pH 2.5 buffer contained 80% of the initial activity, whereas samples prepared in pH 4.5, 6.0, 7.0, and 8.0 buffers contained less than 20%. Laboratory-prepared plasma and serum samples showed an 8% loss in activity when incubated for 6 h at 4 degrees C, a 51% loss when incubated for 6 h at 25 degrees C, and a 48% loss when incubated for 2 h at 37 degrees C. Clinical samples demonstrated a similar stability pattern. Degradation rates for cefaclor in commercially prepared serum increased from 4- to 10-fold in comparison to rates obtained when samples were made in human serum freshly prepared in our laboratory. Consequently, serum standards should be made in freshly prepared human serum.", "contents": "Stability and blood level determinations of cefaclor, a new oral cephalosporin antibiotic. Cefaclor solutions in pH 2.5 and 4.5 buffers contained at least 90% of their initial activity after 72 h at 4 degrees C. Samples in pH 6.0, 7.0, and 8.0 buffers contained 70, 46, and 34%, respectively, of their initial activity after 72 h at 4 degrees C. After 72 h at 25 degrees C, samples prepared with pH 2.5, 4.5, 6.0, 7.0, and 8.0 buffers contained 95, 69, 16, 5, and 3%, respectively, of their initial activity. After 72 h at 37 degrees C, cefaclor solutions in pH 2.5 buffer contained 80% of the initial activity, whereas samples prepared in pH 4.5, 6.0, 7.0, and 8.0 buffers contained less than 20%. Laboratory-prepared plasma and serum samples showed an 8% loss in activity when incubated for 6 h at 4 degrees C, a 51% loss when incubated for 6 h at 25 degrees C, and a 48% loss when incubated for 2 h at 37 degrees C. Clinical samples demonstrated a similar stability pattern. Degradation rates for cefaclor in commercially prepared serum increased from 4- to 10-fold in comparison to rates obtained when samples were made in human serum freshly prepared in our laboratory. Consequently, serum standards should be made in freshly prepared human serum."}
{"id": "PMID:24425", "title": "Mal perforans and spina bifida occulta.", "content": "A 26-year-old man had mal perforans pedis as the principal manifestation of spina bifida occulta with an associated intradural lipoma. Two lumbosacral dimples and a tuft of hair overlying the spina bifida led to the diagnosis. We include a review of the causes of mal perforans and a review of spina bifida occulta and associated abnormalities.", "contents": "Mal perforans and spina bifida occulta. A 26-year-old man had mal perforans pedis as the principal manifestation of spina bifida occulta with an associated intradural lipoma. Two lumbosacral dimples and a tuft of hair overlying the spina bifida led to the diagnosis. We include a review of the causes of mal perforans and a review of spina bifida occulta and associated abnormalities."}
{"id": "PMID:24426", "title": "Alclofenac and D-penicillamine. Comparative trial in rheumatoid arthritis.", "content": "Forty-six patients with rheumatoid arthritis, 22 receiving D-penicillamine and 2j alclofenac, took part in a 6-month single-bind external observer trial to compare the efficacy and toxicity of these drugs in the treatment of severe rheumatoid arthritis. Both drugs were active and similar in their efficacy at 6 months as judged by clinical and laboratory measurements. Penicillamine was active therapeutically by 3 months, one month before alclofenac. 9 patients, 8 on alclofenac and one on D-penicillamine, had to stop treatment because of lack of effect or toxic effects. Skin rashes within the first week of treatment were a major problem with alclofenac and led to 6 withdrawals.", "contents": "Alclofenac and D-penicillamine. Comparative trial in rheumatoid arthritis. Forty-six patients with rheumatoid arthritis, 22 receiving D-penicillamine and 2j alclofenac, took part in a 6-month single-bind external observer trial to compare the efficacy and toxicity of these drugs in the treatment of severe rheumatoid arthritis. Both drugs were active and similar in their efficacy at 6 months as judged by clinical and laboratory measurements. Penicillamine was active therapeutically by 3 months, one month before alclofenac. 9 patients, 8 on alclofenac and one on D-penicillamine, had to stop treatment because of lack of effect or toxic effects. Skin rashes within the first week of treatment were a major problem with alclofenac and led to 6 withdrawals."}
{"id": "PMID:24428", "title": "Evaluation of physician assistants in rural primary care.", "content": "The advent of physician assistants raises questions regarding their appropriate utilization and monitoring. To determine practice patterns of physician assistants in settings independent of training programs, we studied 14 primary care practices in the rural southeast. Detailed observations, including appropriateness of medical care, were made on 788 outpatient-provider encounters. Physician assistants handled minor medical problems well and 61% of the patients observed in these practices fitted this category. Three practice patterns were observed: all patients were seen by the assistant initially, followed by the physician; patients managed concurrently by physician and assistant were not preselected; and patients with specific problems were assigned to the assistant. Properly managed, each of these patterns yielded competent care. Using these observations, proposed models of management and audit are presented for each practice pattern.", "contents": "Evaluation of physician assistants in rural primary care. The advent of physician assistants raises questions regarding their appropriate utilization and monitoring. To determine practice patterns of physician assistants in settings independent of training programs, we studied 14 primary care practices in the rural southeast. Detailed observations, including appropriateness of medical care, were made on 788 outpatient-provider encounters. Physician assistants handled minor medical problems well and 61% of the patients observed in these practices fitted this category. Three practice patterns were observed: all patients were seen by the assistant initially, followed by the physician; patients managed concurrently by physician and assistant were not preselected; and patients with specific problems were assigned to the assistant. Properly managed, each of these patterns yielded competent care. Using these observations, proposed models of management and audit are presented for each practice pattern."}
{"id": "PMID:24429", "title": "Allergic angiitis and granulomatosis. Prolonged remission induced by combined prednisone--azathioprine therapy.", "content": "Two patients with acute, rapidly progressive generalized vasculitis initially had symptoms of asthma. Progressive increase in severity of asthma was followed by systemic disease, including pulmonary infiltrative disease, mononeuritis multiplex, and abdominal pain. Examination of the tissues demonstrated vasculitis with eosinophilia, and clinically both cases appeared in a near terminal state. High-dose prednisone did not induce a remission. In particular, the lesions of mononeuritis multiplex progressed after initiation of high-dose prednisone. The addition of azathioprine to the regimen was followed by a gradual and then complete remission of clinical and laboratory abnormalities, except for some residual nerve damage and asthma of varying severity in the two patients. These two patients, whose cases are classified as the allergic granulomatosis variant of polyarteritis nodosa, have had a remission of seven and almost two years, respectively, after combined prednisone-azathioprine therapy.", "contents": "Allergic angiitis and granulomatosis. Prolonged remission induced by combined prednisone--azathioprine therapy. Two patients with acute, rapidly progressive generalized vasculitis initially had symptoms of asthma. Progressive increase in severity of asthma was followed by systemic disease, including pulmonary infiltrative disease, mononeuritis multiplex, and abdominal pain. Examination of the tissues demonstrated vasculitis with eosinophilia, and clinically both cases appeared in a near terminal state. High-dose prednisone did not induce a remission. In particular, the lesions of mononeuritis multiplex progressed after initiation of high-dose prednisone. The addition of azathioprine to the regimen was followed by a gradual and then complete remission of clinical and laboratory abnormalities, except for some residual nerve damage and asthma of varying severity in the two patients. These two patients, whose cases are classified as the allergic granulomatosis variant of polyarteritis nodosa, have had a remission of seven and almost two years, respectively, after combined prednisone-azathioprine therapy."}
{"id": "PMID:24430", "title": "[Selective local hyperthermy of tumor tissue. Homogenized energy supply also to deep-seated tissues by high-performance decametric wave coil section plus dual system raster motion (author's transl)].", "content": "Based on results of selective tumor tissue hyperacidification and whole-body hyperthermy the paper deals with the advantages of local hyperthermy and gives a review of the various methods of energy supply for hyperthermy in living tissue. It follows a presentation of physical and biophysical fundamentals on selective local hyperthermy of tumor tissue by radiation, by r. f. rotational magnetic fields and by r. f. capacitor fields. Using a gelatine phantom for measuring the energy supply with the various modes of local hyperthermy it is then shown that it is solely the divergent rotational magnetic field which allows to substantially reduce the inhomogeneity of energy supply also in z-direction (increasing depth in body tissue) by introducing a relative raster motion of the applicator in x-y-direction (plane parallel to body surface). It is only the introduction of the x-y raster principle combined with a described dual system array (CMT Selectotherm System) which permits the high and rather homogeneous supply of thermal energy also to deep-seated tumor tissue in the patient without concomitant critical superheating of tissues near the skin. Finally the paper gives a theoretical derivation of the temperature profile for selective local hyperthermy of tumor tissue. With due consideration of heat dissipation by convection and conduction, this endeavour shows rather promising aspects for the therapeutic efficiency obtainable in each case of treatment.", "contents": "[Selective local hyperthermy of tumor tissue. Homogenized energy supply also to deep-seated tissues by high-performance decametric wave coil section plus dual system raster motion (author's transl)]. Based on results of selective tumor tissue hyperacidification and whole-body hyperthermy the paper deals with the advantages of local hyperthermy and gives a review of the various methods of energy supply for hyperthermy in living tissue. It follows a presentation of physical and biophysical fundamentals on selective local hyperthermy of tumor tissue by radiation, by r. f. rotational magnetic fields and by r. f. capacitor fields. Using a gelatine phantom for measuring the energy supply with the various modes of local hyperthermy it is then shown that it is solely the divergent rotational magnetic field which allows to substantially reduce the inhomogeneity of energy supply also in z-direction (increasing depth in body tissue) by introducing a relative raster motion of the applicator in x-y-direction (plane parallel to body surface). It is only the introduction of the x-y raster principle combined with a described dual system array (CMT Selectotherm System) which permits the high and rather homogeneous supply of thermal energy also to deep-seated tumor tissue in the patient without concomitant critical superheating of tissues near the skin. Finally the paper gives a theoretical derivation of the temperature profile for selective local hyperthermy of tumor tissue. With due consideration of heat dissipation by convection and conduction, this endeavour shows rather promising aspects for the therapeutic efficiency obtainable in each case of treatment."}
{"id": "PMID:24431", "title": "Anxiety, arousal, and autonomic habituation.", "content": "The interaction of anxiety and autonomic activation as a factor in the development and persistency of pathological anxiety was investigated with the aid of self-rating procedures and a habituation experiment. The state of activation was varied systematically in 40 normal subjects by various experimental conditions and by the administration of a tranquilizer. The degree of anxiety and activation were able to be differentiated in the investigated range of mean attentiveness. Anxious expectancy is perceived in particular as subjective anxiety. Fatigue and sedation, on the other hand, demonstrate subjective and autonomic desactivation. Corresponding differences can be demonstrated for the anxiolytic and sedative effects of tranquilizers. The time course of habituation is a more exact indicator than the amplitude of the orienting response. Cognitively provoked apprehensiveness, thus, appears to be qualitatively different as compared to psychoautonomically caused anxieties of psychiatric disorders.", "contents": "Anxiety, arousal, and autonomic habituation. The interaction of anxiety and autonomic activation as a factor in the development and persistency of pathological anxiety was investigated with the aid of self-rating procedures and a habituation experiment. The state of activation was varied systematically in 40 normal subjects by various experimental conditions and by the administration of a tranquilizer. The degree of anxiety and activation were able to be differentiated in the investigated range of mean attentiveness. Anxious expectancy is perceived in particular as subjective anxiety. Fatigue and sedation, on the other hand, demonstrate subjective and autonomic desactivation. Corresponding differences can be demonstrated for the anxiolytic and sedative effects of tranquilizers. The time course of habituation is a more exact indicator than the amplitude of the orienting response. Cognitively provoked apprehensiveness, thus, appears to be qualitatively different as compared to psychoautonomically caused anxieties of psychiatric disorders."}
{"id": "PMID:24432", "title": "Purification of human diploid fibroblast interferon by immobilized neuraminidase.", "content": "An efficient method for the purification of human fibroblast interferon (IF) based on binding via the N-acetyl neuraminic acid (N-ANA) residue of the IF molecules to the immobilized neuraminidase has been developed. Binding of IF occurred at pH 4.5 and elution of the bound activity was effected at pH 9.5. Specific activity of IF in the alkaline eluate was increased by a factor in excess of 200 and the IF thus recovered had probably retained most of the N-ANA moieties.", "contents": "Purification of human diploid fibroblast interferon by immobilized neuraminidase. An efficient method for the purification of human fibroblast interferon (IF) based on binding via the N-acetyl neuraminic acid (N-ANA) residue of the IF molecules to the immobilized neuraminidase has been developed. Binding of IF occurred at pH 4.5 and elution of the bound activity was effected at pH 9.5. Specific activity of IF in the alkaline eluate was increased by a factor in excess of 200 and the IF thus recovered had probably retained most of the N-ANA moieties."}
{"id": "PMID:24433", "title": "[State of the microcirculation in periarteritis nodosa based on morphological and biomicroscopic data].", "content": "The status of microcirculation in periarteritis nodosa was studied by impregnation method (serous membranes) and biomicroscopy (eyeball conjunctiva). Pathological and adaptative changes in terminal vessels were found. It is suggested that the involvement of microcirculation ways in this disease is systemic and that morphological changes in microvessels are comparable to biomicroscopic changes.", "contents": "[State of the microcirculation in periarteritis nodosa based on morphological and biomicroscopic data]. The status of microcirculation in periarteritis nodosa was studied by impregnation method (serous membranes) and biomicroscopy (eyeball conjunctiva). Pathological and adaptative changes in terminal vessels were found. It is suggested that the involvement of microcirculation ways in this disease is systemic and that morphological changes in microvessels are comparable to biomicroscopic changes."}
{"id": "PMID:24436", "title": "Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions.", "content": "1. Each of five triorganotin and five triorganolead compounds was shown to perturb mithochondrial functions in three different ways. One is dependent and two are independent of Cl- in the medium. 2. Structure-activity relationships for the three interactions are described, and compounds suitable as tools for the separate study of each process are defined. 3. In a Cl- -containing medium trimethyltin, triethyltin, trimethyl-lead, triethyl-lead and tri-n-propyl-lead all produce the same maximum rate of ATP hydrolysis and O2 uptake; this rate is much less than that produced by uncoupling agents such as 2,4-dinitrophenol. 4. Increase in ATP hydrolysis and O2 uptake are measures on energy ultilization when triogranotin and triorganolead compounds bring about an exchange of external C1- for intramitochondrial OH- ions. Possible rate-limiting steps in this process are discussed. 5. In a C1- -containing medium ATP synthesis linked to the oxidation of beta-hydroxybutyrate or reduced cytochrone c is less inhibited by triethyltin or triethyl-lead than is ATP synthesis linked to the oxidation of succinate, pyruvate or L-glutamate. 6. The inhibition of ATP synthesis linked to the oxidation of both beta-hydroxybutyrate and reduced cytochrome c consists of two processes: one is a limited uncoupling and is C1- -dependent and the other is a C1- -independent inhibition of the energy-conservation system. 7. The different sensitivities to inhibition by triethyltin of mitochondrial functions involving the oxidation of beta-hydroxybutyrate and succinate are compared and discussed.", "contents": "Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions. 1. Each of five triorganotin and five triorganolead compounds was shown to perturb mithochondrial functions in three different ways. One is dependent and two are independent of Cl- in the medium. 2. Structure-activity relationships for the three interactions are described, and compounds suitable as tools for the separate study of each process are defined. 3. In a Cl- -containing medium trimethyltin, triethyltin, trimethyl-lead, triethyl-lead and tri-n-propyl-lead all produce the same maximum rate of ATP hydrolysis and O2 uptake; this rate is much less than that produced by uncoupling agents such as 2,4-dinitrophenol. 4. Increase in ATP hydrolysis and O2 uptake are measures on energy ultilization when triogranotin and triorganolead compounds bring about an exchange of external C1- for intramitochondrial OH- ions. Possible rate-limiting steps in this process are discussed. 5. In a C1- -containing medium ATP synthesis linked to the oxidation of beta-hydroxybutyrate or reduced cytochrone c is less inhibited by triethyltin or triethyl-lead than is ATP synthesis linked to the oxidation of succinate, pyruvate or L-glutamate. 6. The inhibition of ATP synthesis linked to the oxidation of both beta-hydroxybutyrate and reduced cytochrome c consists of two processes: one is a limited uncoupling and is C1- -dependent and the other is a C1- -independent inhibition of the energy-conservation system. 7. The different sensitivities to inhibition by triethyltin of mitochondrial functions involving the oxidation of beta-hydroxybutyrate and succinate are compared and discussed."}
{"id": "PMID:24437", "title": "Demonstration of the phosphorylation of acetyl-coenzyme A carboxylase within intact rat epididymal fat-cells.", "content": "Intact rat epididymal fat-cells were incubated with 32Pi and the intracellular proteins separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. One of the phosphorylated proteins has the same RF value as [14C]biotin-labelled acetyl-CoA carboxylase purified from fat-cells and is specifically precipitated after incubation with antiserum raised against acetyl-CoA carboxylase. No significant changes in the extent of phosphorylation of acetyl-CoA carboxylase were detected after exposure of the cells to insulin.", "contents": "Demonstration of the phosphorylation of acetyl-coenzyme A carboxylase within intact rat epididymal fat-cells. Intact rat epididymal fat-cells were incubated with 32Pi and the intracellular proteins separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. One of the phosphorylated proteins has the same RF value as [14C]biotin-labelled acetyl-CoA carboxylase purified from fat-cells and is specifically precipitated after incubation with antiserum raised against acetyl-CoA carboxylase. No significant changes in the extent of phosphorylation of acetyl-CoA carboxylase were detected after exposure of the cells to insulin."}
{"id": "PMID:24438", "title": "Isolation of proteoglycans from human articular cartilage.", "content": "Proteoglycans were extracted from normal human articular cartilage of various ages with 4M-guanidinium chloride and were purified and characterized by using preformed linear CsCl density gradients. With advancing age, there was a decrease in high-density proteoglycans of low protein/uronic acid weight ratio and an increase in the proportion of lower-density proteoglycans, richer in keratan sulphate and protein. Proteoglycans of each age were also shown to disaggregate in 4M-guanidinium chloride and at low pH and to reaggregate in the presence of hyaluronic acid and/or low-density fractions. Osteoarthrotic-cartilage extracts had an increased content of higher-density proteoglycans compared with normal cartilage of the same age, and results also suggested that these were not mechanical or enzymic degradation products, but were possibly proteoglycans of an immature nature.", "contents": "Isolation of proteoglycans from human articular cartilage. Proteoglycans were extracted from normal human articular cartilage of various ages with 4M-guanidinium chloride and were purified and characterized by using preformed linear CsCl density gradients. With advancing age, there was a decrease in high-density proteoglycans of low protein/uronic acid weight ratio and an increase in the proportion of lower-density proteoglycans, richer in keratan sulphate and protein. Proteoglycans of each age were also shown to disaggregate in 4M-guanidinium chloride and at low pH and to reaggregate in the presence of hyaluronic acid and/or low-density fractions. Osteoarthrotic-cartilage extracts had an increased content of higher-density proteoglycans compared with normal cartilage of the same age, and results also suggested that these were not mechanical or enzymic degradation products, but were possibly proteoglycans of an immature nature."}
{"id": "PMID:24439", "title": "Activation of immobilized acetyl-Coenzyme A carboxylase.", "content": "Partially purified acetyl-CoA carboxylase was covalently bound to a Sepharose 4B matrix. Although aggregation was thus prevented, the enzymic activity was stimulated by citrate and isocitrate.", "contents": "Activation of immobilized acetyl-Coenzyme A carboxylase. Partially purified acetyl-CoA carboxylase was covalently bound to a Sepharose 4B matrix. Although aggregation was thus prevented, the enzymic activity was stimulated by citrate and isocitrate."}
{"id": "PMID:24440", "title": "Synthesis of the native copper(II)-transport site of human serum albumin and its copper(II)-binding properties.", "content": "A derivative of the native-sequence tripeptide of the specific Cu(II)-transport site of human serum albumin, L-aspartyl-L-alanyl-L-histidine N-methylamide, was synthesized, and its binding to Cu(II) was examined to determine the influence of the side-chain groups on the Cu(II) binding. The equilibria involved in the Cu(II)-L-aspartyl-L-alanyl-L-histidine N-methylamide system were investigated by analytical potentiometry. Three complex species were found in the pH range 4-10. The same species were identified in both the visible and circular-dichroism spectra. The main species present in the physiological pH range is shown to have the same ligands around the square-planar Cu(II) ion as those reported for albumin and tripeptides diglycyl-L-histidine and its N-methylamide derivative. The results obtained from competition experiments showed that this tripeptide has a higher affinity towards Cu(II) than has albumin itself. The overall findings are compared with those from albumin. At neutral pH the side chains do not play any important role in the Cu(II) binding, but at low pH the beta-carboxyl group of the N-terminal aspartic residue becomes important. A possible competition site on albumin for Cu(II) at low pH is discussed.", "contents": "Synthesis of the native copper(II)-transport site of human serum albumin and its copper(II)-binding properties. A derivative of the native-sequence tripeptide of the specific Cu(II)-transport site of human serum albumin, L-aspartyl-L-alanyl-L-histidine N-methylamide, was synthesized, and its binding to Cu(II) was examined to determine the influence of the side-chain groups on the Cu(II) binding. The equilibria involved in the Cu(II)-L-aspartyl-L-alanyl-L-histidine N-methylamide system were investigated by analytical potentiometry. Three complex species were found in the pH range 4-10. The same species were identified in both the visible and circular-dichroism spectra. The main species present in the physiological pH range is shown to have the same ligands around the square-planar Cu(II) ion as those reported for albumin and tripeptides diglycyl-L-histidine and its N-methylamide derivative. The results obtained from competition experiments showed that this tripeptide has a higher affinity towards Cu(II) than has albumin itself. The overall findings are compared with those from albumin. At neutral pH the side chains do not play any important role in the Cu(II) binding, but at low pH the beta-carboxyl group of the N-terminal aspartic residue becomes important. A possible competition site on albumin for Cu(II) at low pH is discussed."}
{"id": "PMID:24441", "title": "The binding of copper ions to copper-free bovine superoxide dismutase. Kinetic aspects.", "content": "The kinetics of reconstitution of bovine superoxide dismutase from Cu2+ and the copper-free enzyme have been studied by activity, u.v.-absorption, electron-paramagnetic-resonance and pulsed-nuclear-magnetic-resonance measurements. The process appears to be first-order up to 80% completion in most conditions, and is pH-dependent, with an apparent pK of 6.5. U.v.-absorption and solvent proton relaxation rate measurements show that fast binding of Cu2+ occurs, and the initial ligands are likely to be, at least in part, those of the native active site. The recovery of the native activity and spectroscopic properties is a slow process with activation energies of 92 kJ/mol at pH 5.3 and 8.4kJ/mol at pH 8.1 and can be described as a rearrangement of the site around the bound metal. The rate of this process is lower in partially recombined protein samples, probably because of intersubunit interactions.", "contents": "The binding of copper ions to copper-free bovine superoxide dismutase. Kinetic aspects. The kinetics of reconstitution of bovine superoxide dismutase from Cu2+ and the copper-free enzyme have been studied by activity, u.v.-absorption, electron-paramagnetic-resonance and pulsed-nuclear-magnetic-resonance measurements. The process appears to be first-order up to 80% completion in most conditions, and is pH-dependent, with an apparent pK of 6.5. U.v.-absorption and solvent proton relaxation rate measurements show that fast binding of Cu2+ occurs, and the initial ligands are likely to be, at least in part, those of the native active site. The recovery of the native activity and spectroscopic properties is a slow process with activation energies of 92 kJ/mol at pH 5.3 and 8.4kJ/mol at pH 8.1 and can be described as a rearrangement of the site around the bound metal. The rate of this process is lower in partially recombined protein samples, probably because of intersubunit interactions."}
{"id": "PMID:24442", "title": "Partial purification and characterization of a pyruvate dehydrogenase-complex-inactivating enzyme from rat liver.", "content": "An enzyme inactivating the pyruvate dehydrogenase complex (inactivase) was purified about 8000-fold from rat liver by differential centrifugation, acid extraction of a lysosomerich 25000 g pellet, acetone fractionation, and adsorption on calcium phosphate gel. By exclusion chromatography on Sephadex G-100 a molecular weight of 21 000 was estimated. The purified enzyme was most stable at pH 5.8 in potassium phosphate buffer, and at pH 4.5 in McIlvaine buffer. At high dilutions the enzyme was very labile and was remarkably stabilized by high salt concentrations. Enzyme activity is inhibited by native rat blood serum, iodoacetamide and leupeptin, but not by phenylmethanesulphonyl fluoride, suggesting that it belongs to the class of thiol proteinases. Among various enzymes tested, only 2-oxoglutarate dehydrogenase was attacked by the inactivase to a similar extent to the pyruvate dehydrogenase complex. Studies on the inactivation mechanism indicate that although the overall reaction is completely lost after treatment with inactivase, each individual step of the multienzyme complex retains full catalytic activity. As judged from sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the transacetylase subunit appears to be degraded into several smaller fractions.", "contents": "Partial purification and characterization of a pyruvate dehydrogenase-complex-inactivating enzyme from rat liver. An enzyme inactivating the pyruvate dehydrogenase complex (inactivase) was purified about 8000-fold from rat liver by differential centrifugation, acid extraction of a lysosomerich 25000 g pellet, acetone fractionation, and adsorption on calcium phosphate gel. By exclusion chromatography on Sephadex G-100 a molecular weight of 21 000 was estimated. The purified enzyme was most stable at pH 5.8 in potassium phosphate buffer, and at pH 4.5 in McIlvaine buffer. At high dilutions the enzyme was very labile and was remarkably stabilized by high salt concentrations. Enzyme activity is inhibited by native rat blood serum, iodoacetamide and leupeptin, but not by phenylmethanesulphonyl fluoride, suggesting that it belongs to the class of thiol proteinases. Among various enzymes tested, only 2-oxoglutarate dehydrogenase was attacked by the inactivase to a similar extent to the pyruvate dehydrogenase complex. Studies on the inactivation mechanism indicate that although the overall reaction is completely lost after treatment with inactivase, each individual step of the multienzyme complex retains full catalytic activity. As judged from sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the transacetylase subunit appears to be degraded into several smaller fractions."}
{"id": "PMID:24443", "title": "Fatty acid synthesis in the regenerating liver of the rat.", "content": "1. Synthesis de novo of fatty acids in the rat liver, measured per g wet wt. of tissue, was increased by a factor of about two, between 1 and 4 days after partial hepatectomy, compared with rates in sham-operated control rat livers. 2. There were no associated changes in the rates of liver cholesterol synthesis or of adipose-tissue fatty acid synthesis in rats after partial hepatectomy, compared with rates in sham-operated rats. 3. In regenerating livers, perfused under three different conditions, there was no alteration in the capacity for fatty acid synthesis compared with that of control rats. 4. The increased synthesis of fatty acids in regenerating liver was associated with insignificant increases in plasma concentrations of tricylglycerols and free fatty acids, with a decrease in content of liver glycogen, and with no change in hepatic activity of acetyl-CoA carboxylase. 5. The accelerated rate of synthesis of fatty adids in regenerating liver appears not to be due to any intrinsic alteration in hepatic capacity for fatty acid synthesis, but it may be caused by the continuous action on liver of unidentified circulating factors.", "contents": "Fatty acid synthesis in the regenerating liver of the rat. 1. Synthesis de novo of fatty acids in the rat liver, measured per g wet wt. of tissue, was increased by a factor of about two, between 1 and 4 days after partial hepatectomy, compared with rates in sham-operated control rat livers. 2. There were no associated changes in the rates of liver cholesterol synthesis or of adipose-tissue fatty acid synthesis in rats after partial hepatectomy, compared with rates in sham-operated rats. 3. In regenerating livers, perfused under three different conditions, there was no alteration in the capacity for fatty acid synthesis compared with that of control rats. 4. The increased synthesis of fatty acids in regenerating liver was associated with insignificant increases in plasma concentrations of tricylglycerols and free fatty acids, with a decrease in content of liver glycogen, and with no change in hepatic activity of acetyl-CoA carboxylase. 5. The accelerated rate of synthesis of fatty adids in regenerating liver appears not to be due to any intrinsic alteration in hepatic capacity for fatty acid synthesis, but it may be caused by the continuous action on liver of unidentified circulating factors."}
{"id": "PMID:24454", "title": "The extraction of antiepileptic drugs. Model study on partition coefficients.", "content": "To compare the extraction behaviour of hexane, toluene, chloroform, 1,2-dichloroethane, diethylether, ethyl acetate and acetone towards phenobarbital, phenytoin, primidone and carbamazepine, partition coefficients of these drugs between the above solvents and water (saturated with ammonium sulphate when working with acetone) were measured at different pH-conditions. Acetone rendered the highest partition coefficients for all drugs. Ethyl acetate was second in the range, except for carbamazepine, which showed a specific affinity for the chlorinated hydrocarbons.", "contents": "The extraction of antiepileptic drugs. Model study on partition coefficients. To compare the extraction behaviour of hexane, toluene, chloroform, 1,2-dichloroethane, diethylether, ethyl acetate and acetone towards phenobarbital, phenytoin, primidone and carbamazepine, partition coefficients of these drugs between the above solvents and water (saturated with ammonium sulphate when working with acetone) were measured at different pH-conditions. Acetone rendered the highest partition coefficients for all drugs. Ethyl acetate was second in the range, except for carbamazepine, which showed a specific affinity for the chlorinated hydrocarbons."}
{"id": "PMID:24458", "title": "Intracellular localization of hepatic propionyl-CoA carboxylase and methylmalonyl-CoA mutase in humans and normal and vitamin B12 deficient rats.", "content": "The intracellular localization of the enzymes in the vitamin B12 dependent pathway which involves the oxidation of propionate was studied in rat liver obtained from normal and vitamin B12 deficient rats as well as from man. The subcellular site of propionyl CoA carboxylase and the vitamin B12 dependent-methylmalonyl CoA mutase were determined. All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria. Vitamin B12 deficiency did not alter the subcellular localization. Finally, a rapid enzymatic assay for methylmalonyl-CoA mutase was described.", "contents": "Intracellular localization of hepatic propionyl-CoA carboxylase and methylmalonyl-CoA mutase in humans and normal and vitamin B12 deficient rats. The intracellular localization of the enzymes in the vitamin B12 dependent pathway which involves the oxidation of propionate was studied in rat liver obtained from normal and vitamin B12 deficient rats as well as from man. The subcellular site of propionyl CoA carboxylase and the vitamin B12 dependent-methylmalonyl CoA mutase were determined. All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria. Vitamin B12 deficiency did not alter the subcellular localization. Finally, a rapid enzymatic assay for methylmalonyl-CoA mutase was described."}
{"id": "PMID:24459", "title": "Metabolic effects of beta-sympathomimetic drugs and dexamethasone in normal and diabetic pregnancy.", "content": "Marked hyperglycaemia and hyperinsulinaemia were observed in two normal women in premature labour treated with an intravenous infusion of a beta-sympathomimetic drug and intramuscular dexamethasone injections. Similar therapy in a chemical diabetic patient caused diabetic ketoacidosis, while treatment of an insulin dependent diabetic with dexamethasone alone resulted in a major increase in her insulin requirements. It is suggested that the diabetogenic effects of beta-sympathomimetic drugs and dexamethasone may be additive and that regular plasma glucose estimations should be made when they are used, especially in patients with impaired glucose tolerance.", "contents": "Metabolic effects of beta-sympathomimetic drugs and dexamethasone in normal and diabetic pregnancy. Marked hyperglycaemia and hyperinsulinaemia were observed in two normal women in premature labour treated with an intravenous infusion of a beta-sympathomimetic drug and intramuscular dexamethasone injections. Similar therapy in a chemical diabetic patient caused diabetic ketoacidosis, while treatment of an insulin dependent diabetic with dexamethasone alone resulted in a major increase in her insulin requirements. It is suggested that the diabetogenic effects of beta-sympathomimetic drugs and dexamethasone may be additive and that regular plasma glucose estimations should be made when they are used, especially in patients with impaired glucose tolerance."}
{"id": "PMID:24460", "title": "Renal tubular function in normal pregnancy.", "content": "Maternal plasma and urine concentrations of beta2- microglobulin and gamma-glutamyl transpeptidase (EC:2.3.2.2) were measured serially in normal pregnancy. These parameters remained constant throughout and can therefore be used to evaluate tubular function in pregnancies complicated by renal disorders.", "contents": "Renal tubular function in normal pregnancy. Maternal plasma and urine concentrations of beta2- microglobulin and gamma-glutamyl transpeptidase (EC:2.3.2.2) were measured serially in normal pregnancy. These parameters remained constant throughout and can therefore be used to evaluate tubular function in pregnancies complicated by renal disorders."}
{"id": "PMID:24462", "title": "Electron spin resonance and nuclear relaxation studies on spin-labeled glutamate dehydrogenase.", "content": "The reaction of glutamate dehydrogenase with two different stable nitroxides (spin labels) is reported. The two compounds contain a carbonyl and an iodoacetamide group as their reactive parts. The carbonyl compound inactivates the enzyme by the formation of a 1:1 covalent complex after NaBH4 reduction of an intermediate Schiff's base. Evidence indicates that the enzyme is modified at lysine-126 in the active site. The electron spin resonance (ESR) spectrum of spin-labeled enzyme indicates a high degree of immobilization of the nitroxide. The binding of reduced coenzyme NADPH is reflected by a change (immobilization) of the ESR spectrum. Nuclear relaxation of bound substrate, oxidized coenzyme, and inhibitor by the paramagnetic group is observed. This shows the existence of a binding site for these compounds close to the active site. The distances of selected protons of the binding ligands to the nitroxide are calculated. The iodoacetamide spin label reacts with several groups, one of which is not a sulfhydryl. The reaction of this particular group causes inactivation of the enzyme. Protection against this inactivation could be achieved with certain ligands. Only enzyme that was spin labeled without such protection caused paramagnetic relaxation of bound substrate and coenzyme.", "contents": "Electron spin resonance and nuclear relaxation studies on spin-labeled glutamate dehydrogenase. The reaction of glutamate dehydrogenase with two different stable nitroxides (spin labels) is reported. The two compounds contain a carbonyl and an iodoacetamide group as their reactive parts. The carbonyl compound inactivates the enzyme by the formation of a 1:1 covalent complex after NaBH4 reduction of an intermediate Schiff's base. Evidence indicates that the enzyme is modified at lysine-126 in the active site. The electron spin resonance (ESR) spectrum of spin-labeled enzyme indicates a high degree of immobilization of the nitroxide. The binding of reduced coenzyme NADPH is reflected by a change (immobilization) of the ESR spectrum. Nuclear relaxation of bound substrate, oxidized coenzyme, and inhibitor by the paramagnetic group is observed. This shows the existence of a binding site for these compounds close to the active site. The distances of selected protons of the binding ligands to the nitroxide are calculated. The iodoacetamide spin label reacts with several groups, one of which is not a sulfhydryl. The reaction of this particular group causes inactivation of the enzyme. Protection against this inactivation could be achieved with certain ligands. Only enzyme that was spin labeled without such protection caused paramagnetic relaxation of bound substrate and coenzyme."}
{"id": "PMID:24463", "title": "Raman spectra of heme a, cytochrome oxidase-ligand complexes, and alkaline denatured oxidase.", "content": "We report 441.6 nm excitation resonance Raman spectra of oxidized and reduced monomeric heme a-imidazole, cytochrome oxidase-exogenous ligand complexes in various redox states, and alkaline denatured oxidase. These data show that, in reduced oxidase, the cytochrome a3 Raman spectrum has bands at 215, 364, 1230, and 1670 cm-1 not observed in the cytochrome a spectrum. The appearance of these bands in the reduced cytochrome a3 spectrum is due to interactions between the heme a of cytochrome a3 and its protein environment and not to intrinsic properties of heme a. These interactions are pH sensitive and strongly influence the vibrational spectra of both heme a groups. We assign the 1670-cm-1 band to the heme a formyl substituent and propose that the intensity of the 1670 cm-1 is high for reduced cytochrome a3 because the C==O lies in the porphyrin plane and is very weak for oxidized and reduced cytochrome a, oxidized cytochrome a3, and oxidized and reduced heme a-imidazole because the C==O lies out of the plane. We suggest that movement of the C==O in and out of the plane explains the ligand induced spectral shift in the optical absorption spectrum of reduced cytochrome a3. Finally, we confirm the observation of Adar & Yonetani (private communication) that, under laser illumination, resting oxidase is photoreactive.", "contents": "Raman spectra of heme a, cytochrome oxidase-ligand complexes, and alkaline denatured oxidase. We report 441.6 nm excitation resonance Raman spectra of oxidized and reduced monomeric heme a-imidazole, cytochrome oxidase-exogenous ligand complexes in various redox states, and alkaline denatured oxidase. These data show that, in reduced oxidase, the cytochrome a3 Raman spectrum has bands at 215, 364, 1230, and 1670 cm-1 not observed in the cytochrome a spectrum. The appearance of these bands in the reduced cytochrome a3 spectrum is due to interactions between the heme a of cytochrome a3 and its protein environment and not to intrinsic properties of heme a. These interactions are pH sensitive and strongly influence the vibrational spectra of both heme a groups. We assign the 1670-cm-1 band to the heme a formyl substituent and propose that the intensity of the 1670 cm-1 is high for reduced cytochrome a3 because the C==O lies in the porphyrin plane and is very weak for oxidized and reduced cytochrome a, oxidized cytochrome a3, and oxidized and reduced heme a-imidazole because the C==O lies out of the plane. We suggest that movement of the C==O in and out of the plane explains the ligand induced spectral shift in the optical absorption spectrum of reduced cytochrome a3. Finally, we confirm the observation of Adar & Yonetani (private communication) that, under laser illumination, resting oxidase is photoreactive."}
{"id": "PMID:24464", "title": "Use of immobilized light-harvesting chlorophyll a/b protein to study the stoichiometry of its self-association.", "content": "D. J. Davis & E. L. Gross (1976) Biochim. Biophys. Acta 449, 554-564 previously observed that the light-harvesting chlorophyll a/b protein or chlorophyll protein complex II self-associated as determined by ultracentrifugation. We have determined the stoichiometry of complex formation by immobilizing the monomer on ethylenediamine-Sepharose 4B and determing the ability of immobilized protein to bind the free protein. The amount of soluble protein bound to the immobilized protein increased as the concentration of soluble protein increased. The binding was maximal between pH 7 and 8. The maximum binding was three molecules bound per one molecule of protein immobilized. These results indicate that a tetramer is the intrinsic structural unit of the light-harvesting chlorophyll a/b protein in the chloroplast membrane. Upon complex formation, the chlorophyll fluorescence was decreased without any spectral change. The maximum binding was approximately doubled upon addition of 0.5 mM CaCl2 whereas 5 mM NaCl had no effect. Addition of CaCl2 had no effect on the fluorescence of the monomer. The light-harvesting chlorophyll a/b protein can be isolated from a sodium lauryl sulfate extract of chloroplasts by affinity  chromatography using the immobilized light-harvesting chlorophyll a/b protein.", "contents": "Use of immobilized light-harvesting chlorophyll a/b protein to study the stoichiometry of its self-association. D. J. Davis & E. L. Gross (1976) Biochim. Biophys. Acta 449, 554-564 previously observed that the light-harvesting chlorophyll a/b protein or chlorophyll protein complex II self-associated as determined by ultracentrifugation. We have determined the stoichiometry of complex formation by immobilizing the monomer on ethylenediamine-Sepharose 4B and determing the ability of immobilized protein to bind the free protein. The amount of soluble protein bound to the immobilized protein increased as the concentration of soluble protein increased. The binding was maximal between pH 7 and 8. The maximum binding was three molecules bound per one molecule of protein immobilized. These results indicate that a tetramer is the intrinsic structural unit of the light-harvesting chlorophyll a/b protein in the chloroplast membrane. Upon complex formation, the chlorophyll fluorescence was decreased without any spectral change. The maximum binding was approximately doubled upon addition of 0.5 mM CaCl2 whereas 5 mM NaCl had no effect. Addition of CaCl2 had no effect on the fluorescence of the monomer. The light-harvesting chlorophyll a/b protein can be isolated from a sodium lauryl sulfate extract of chloroplasts by affinity  chromatography using the immobilized light-harvesting chlorophyll a/b protein."}
{"id": "PMID:24465", "title": "Kinetic analysis of the acid-alkaline conversion of horseradish peroxidases.", "content": "The nature of the acid-alkaline conversion of horseradish peroxidases was studied by measuring four rate constants in reactions, E + H+ (k1) in equilibrium (k2) EH+ and E + H2O (k3) in equilibrium (k4) EH+ + OH-, where EH+ and E denote the acid and alkaline forms of the enzymes. The values of k1, (k2 + k3), and k4 were obtained by measuring the relaxation rates of the acid leads to alkaline and alkaline leads to acid conversions by means of th pH jump method with a stopped-flow apparatus. The value of k3 could also be obtained by measuring the rate of reactions between hydrogen peroxide and peroxidases at alkaline pH. The measurements were conducted with four peroxidases having different pKa values: peroxidase A )pKa = 9.3), peroxidase C (pKa = 11.1), diacetyldeuteroperoxidase A (pKa = 7.7), and diacetyldeuteroperoxidase C (pKa = 9.1). The value of k1 was about 10(10) M-1 s-1 in the reaction of the four enzymes while k4 was quite different between the enzymes. The pKa was determined by k3 and k4 for the natural peroxidases and by k1 and k2 for the diacetyldeuteroperoxidases. The mechanism of the acid-alkaline conversion was discussed in comparison with that of metmyoglobin.", "contents": "Kinetic analysis of the acid-alkaline conversion of horseradish peroxidases. The nature of the acid-alkaline conversion of horseradish peroxidases was studied by measuring four rate constants in reactions, E + H+ (k1) in equilibrium (k2) EH+ and E + H2O (k3) in equilibrium (k4) EH+ + OH-, where EH+ and E denote the acid and alkaline forms of the enzymes. The values of k1, (k2 + k3), and k4 were obtained by measuring the relaxation rates of the acid leads to alkaline and alkaline leads to acid conversions by means of th pH jump method with a stopped-flow apparatus. The value of k3 could also be obtained by measuring the rate of reactions between hydrogen peroxide and peroxidases at alkaline pH. The measurements were conducted with four peroxidases having different pKa values: peroxidase A )pKa = 9.3), peroxidase C (pKa = 11.1), diacetyldeuteroperoxidase A (pKa = 7.7), and diacetyldeuteroperoxidase C (pKa = 9.1). The value of k1 was about 10(10) M-1 s-1 in the reaction of the four enzymes while k4 was quite different between the enzymes. The pKa was determined by k3 and k4 for the natural peroxidases and by k1 and k2 for the diacetyldeuteroperoxidases. The mechanism of the acid-alkaline conversion was discussed in comparison with that of metmyoglobin."}
{"id": "PMID:24468", "title": "The mechanism of oxidation of reduced nicotinamide dinucleotide phosphate by submitochondrial particles from beef heart.", "content": "1. Oxidation of NADPH by various acceptors catalyzed by submitochondrial particles and a partially purified NADH dehydrogenase from beef heart was investigated. Submitochondrial particles devoid of nicotinamide nucleotide transhydrogenase activity catalyze an oxidation of NADPH by oxygen. The partially purified NADH dehydrogenase prepared from these particles catalyzes an oxidation of NADPH by acetylpyridine-NAD. In both cases the rates of oxidation are about two orders of magnitude lower than those obtained with NADH as electron donor. 2. The kinetic characteristics of the NADPH oxidase reaction and reduction of acetylpyridine-NAD by NADPH are similar with regard to pH dependences and affinities for NADPH, indicating that both reactions involve the same binding site for NADPH. The binding of NADPH to this site appears to be rate limiting for the overall reactions. 3. At redox equilibrium NADPH and NADH reduce FMN and iron-sulphur center 1 of NADH dehydrogenase to the same extents. The rate of reduction of FMN by NADPH is at least two orders of magnitude lower than with NADH. 4. It is concluded that NADPH is a substrate of NADH dehydrogenase and that the nicotinamide nucleotide is oxidized by submitochondrial particles via the NADH--binding site of the enzyme.", "contents": "The mechanism of oxidation of reduced nicotinamide dinucleotide phosphate by submitochondrial particles from beef heart. 1. Oxidation of NADPH by various acceptors catalyzed by submitochondrial particles and a partially purified NADH dehydrogenase from beef heart was investigated. Submitochondrial particles devoid of nicotinamide nucleotide transhydrogenase activity catalyze an oxidation of NADPH by oxygen. The partially purified NADH dehydrogenase prepared from these particles catalyzes an oxidation of NADPH by acetylpyridine-NAD. In both cases the rates of oxidation are about two orders of magnitude lower than those obtained with NADH as electron donor. 2. The kinetic characteristics of the NADPH oxidase reaction and reduction of acetylpyridine-NAD by NADPH are similar with regard to pH dependences and affinities for NADPH, indicating that both reactions involve the same binding site for NADPH. The binding of NADPH to this site appears to be rate limiting for the overall reactions. 3. At redox equilibrium NADPH and NADH reduce FMN and iron-sulphur center 1 of NADH dehydrogenase to the same extents. The rate of reduction of FMN by NADPH is at least two orders of magnitude lower than with NADH. 4. It is concluded that NADPH is a substrate of NADH dehydrogenase and that the nicotinamide nucleotide is oxidized by submitochondrial particles via the NADH--binding site of the enzyme."}
{"id": "PMID:24470", "title": "The mechanism of the control of carbon fixation by the pH in the chloroplast stroma. Studies with nitrite-mediated proton transfer across the envelope.", "content": "1. CO2 fixation of intact spinach chloroplasts is inhibited by nitrite in a pH-dependent mode. At pH 7.3 in the medium 1 mM NaNO2 and at pH 7.9 5 mM NaNO2 were required for 50% inhibition. 2. The addition of nitrite leads to an acidificiation in the stroma. It appears that nitrite renders the envelope permeable for protons resulting in a breakdown of the pH gradient between the external space and the stroma. 3. In view of earlier results on the pH sensitivity of C02 fixation it is concluded that this pH shift in the stroma is responsible for the observed inhibition of CO2 fixation by nitrite. 4. Octanoate and to some extent also high concentrations of bicarbonate and acetate have a similar effect as nitrite in inhibiting CO2 fixation through an acidification in the stroma. 5. The levels of the intermediates of the CO2 fixation cycle were measured. A strong rise of the levels of fructose- and sedoheptulose biphosphates and a concomitant decrease of the corresponding monophosphates was observed during inhibition of CO2 fixation. It appears that the enzymatic steps of the CO2 fixation cycle responsible for the overall inhibition of CO2 fixation caused by lowering of the H+ concentration in the stroma are fructose- and sedopheptulose bisphosphatase. These two enzymes have an important function in the light regulation of CO2 fixation.", "contents": "The mechanism of the control of carbon fixation by the pH in the chloroplast stroma. Studies with nitrite-mediated proton transfer across the envelope. 1. CO2 fixation of intact spinach chloroplasts is inhibited by nitrite in a pH-dependent mode. At pH 7.3 in the medium 1 mM NaNO2 and at pH 7.9 5 mM NaNO2 were required for 50% inhibition. 2. The addition of nitrite leads to an acidificiation in the stroma. It appears that nitrite renders the envelope permeable for protons resulting in a breakdown of the pH gradient between the external space and the stroma. 3. In view of earlier results on the pH sensitivity of C02 fixation it is concluded that this pH shift in the stroma is responsible for the observed inhibition of CO2 fixation by nitrite. 4. Octanoate and to some extent also high concentrations of bicarbonate and acetate have a similar effect as nitrite in inhibiting CO2 fixation through an acidification in the stroma. 5. The levels of the intermediates of the CO2 fixation cycle were measured. A strong rise of the levels of fructose- and sedoheptulose biphosphates and a concomitant decrease of the corresponding monophosphates was observed during inhibition of CO2 fixation. It appears that the enzymatic steps of the CO2 fixation cycle responsible for the overall inhibition of CO2 fixation caused by lowering of the H+ concentration in the stroma are fructose- and sedopheptulose bisphosphatase. These two enzymes have an important function in the light regulation of CO2 fixation."}
{"id": "PMID:24471", "title": "Dicarboxylate transport across the inner membrane of the chloroplast envelope.", "content": "The uptake of radioactively labeled dicarboxylates into the sorbitol-impermeable 3H2O space (the space surrounded by the inner envelope membrane) of spinach chloroplasts has been studied by means of silicone layer filtering centrifugation. 1. Malate, aspartate and a number of other dicarboxylates are rapidly transported across the envelope leading to an accumulation in the chloroplasts. This uptake proceeds mainly by a counterexchange with the dicarboxylates present there. 2. The dicarboxylate transport shows saturation characteristics allowing the determination of Km and V. 3. All dicarboxylates transported act as competitive inhibitors of the transport. 4. The activation energy of the transport as determined from the temperature dependency is evaluated to be 7 kcal/mol. 5. The rate of dicarboxylate transport is influenced by illumination, the countertransported molecules and the pH in the medium. These changes effect the transport velocity, whereas the corresponding Km values are not altered. 6. It is discussed whether there is more than one carrier involved in dicarboxylate transport in spinach chloroplasts.", "contents": "Dicarboxylate transport across the inner membrane of the chloroplast envelope. The uptake of radioactively labeled dicarboxylates into the sorbitol-impermeable 3H2O space (the space surrounded by the inner envelope membrane) of spinach chloroplasts has been studied by means of silicone layer filtering centrifugation. 1. Malate, aspartate and a number of other dicarboxylates are rapidly transported across the envelope leading to an accumulation in the chloroplasts. This uptake proceeds mainly by a counterexchange with the dicarboxylates present there. 2. The dicarboxylate transport shows saturation characteristics allowing the determination of Km and V. 3. All dicarboxylates transported act as competitive inhibitors of the transport. 4. The activation energy of the transport as determined from the temperature dependency is evaluated to be 7 kcal/mol. 5. The rate of dicarboxylate transport is influenced by illumination, the countertransported molecules and the pH in the medium. These changes effect the transport velocity, whereas the corresponding Km values are not altered. 6. It is discussed whether there is more than one carrier involved in dicarboxylate transport in spinach chloroplasts."}
{"id": "PMID:24472", "title": "The permeability of the lysosomal membrane to small ions.", "content": "The permeability of the lysosomal membrane to small anions and cations was studied at 37 degrees C and pH 7.0 in a lysosomal-mitochondrial fraction isolated from the liver of untreated rats. The extent of osmotic lysis following ion influx was used as a measure of ion permeancy. In order to preserve electroneutrality, anion influx was coupled to an influx of K+ in the presence of valinomycin, and cation influx was coupled to an efflux of H+ using the protonophore 3-tert-butyl-5,2'-dichloro-4'-nitrosalicilylanilide. Lysosomal lysis was monitored by observing the loss of latency of two lysosomal hydrolases. The order of permeability of the lysosomal membrane to anions was found to be SCN- greater than I- greater than CH3COO- greater than Cl- approximately Pi greater than SO24- and that to cations Cs+ greater than K+ greater than Na+ greater than H+. These orders are largely in agreement with the lyotropic series of anions and cations. The implications of these findings for the mechanism by means of which a low intralysosomal pH is produced and maintained are discussed.", "contents": "The permeability of the lysosomal membrane to small ions. The permeability of the lysosomal membrane to small anions and cations was studied at 37 degrees C and pH 7.0 in a lysosomal-mitochondrial fraction isolated from the liver of untreated rats. The extent of osmotic lysis following ion influx was used as a measure of ion permeancy. In order to preserve electroneutrality, anion influx was coupled to an influx of K+ in the presence of valinomycin, and cation influx was coupled to an efflux of H+ using the protonophore 3-tert-butyl-5,2'-dichloro-4'-nitrosalicilylanilide. Lysosomal lysis was monitored by observing the loss of latency of two lysosomal hydrolases. The order of permeability of the lysosomal membrane to anions was found to be SCN- greater than I- greater than CH3COO- greater than Cl- approximately Pi greater than SO24- and that to cations Cs+ greater than K+ greater than Na+ greater than H+. These orders are largely in agreement with the lyotropic series of anions and cations. The implications of these findings for the mechanism by means of which a low intralysosomal pH is produced and maintained are discussed."}
{"id": "PMID:24473", "title": "Active groups of extracellular endo-D-galacturonanase of aspergillus niger derived from pH effect on kinetic data.", "content": "In an attempt to characterize the groups essential for the catalytic action extracellular endo-D-galacturonanase of Aspergillus niger (poly (1,4-alpha-D-galacturonide) glycanohydrolase, EC 3.2.1.15) the behaviour of the kinetic parameters as a function of pH was examined. The dependence of kcat and kcat/Km on pH suggests that two dissociable groups are involved, for which the pK  values of about 3.0 and 5.0 in the free enzyme and 3.06 and 5.72 in the catalytic complex were found at 30 degrees C. These values and the value of the heat of ionization of the acidic group, deltaHi 6.48 kcal/mol, resulting from the pKa values obtained at 20 degrees C (5.91) and at 30 degrees C (5.72) suggest the participation of a carboxylate group and a protonated imidazole group of histidine in the reaction catalyzed by endo-D-galacturonanase.", "contents": "Active groups of extracellular endo-D-galacturonanase of aspergillus niger derived from pH effect on kinetic data. In an attempt to characterize the groups essential for the catalytic action extracellular endo-D-galacturonanase of Aspergillus niger (poly (1,4-alpha-D-galacturonide) glycanohydrolase, EC 3.2.1.15) the behaviour of the kinetic parameters as a function of pH was examined. The dependence of kcat and kcat/Km on pH suggests that two dissociable groups are involved, for which the pK  values of about 3.0 and 5.0 in the free enzyme and 3.06 and 5.72 in the catalytic complex were found at 30 degrees C. These values and the value of the heat of ionization of the acidic group, deltaHi 6.48 kcal/mol, resulting from the pKa values obtained at 20 degrees C (5.91) and at 30 degrees C (5.72) suggest the participation of a carboxylate group and a protonated imidazole group of histidine in the reaction catalyzed by endo-D-galacturonanase."}
{"id": "PMID:24474", "title": "Effects of melanin on tyrosine hydroxylase and phenylalanine hydroxylase.", "content": "Melanin inhibited rat liver phenylalanine hydroxylase, but activated tyrosine hydroxylase from rat brain (caudate nucleus), rat adrenal glands, and bovine adrenal medulla. Activation of tyrosine hydroxylase by melanin was demonstrated with the extensively dialyzed enzyme and in suboptimal concentrations of the substrate (tyrosine) and the cofactor (6-methyltetrahydropterin). Tyrosine hydroxylase from rat brain was activated by melanin more markedly than that from rat adrenal glands. Purified and extensively dialyzed bovine adrenal tyrosine hydroxylase had two Km values with 6-methyltetrahydropterin, depending upon its concentrations, but the melanin-activated tyrosine hydroxylase had a single Km value and showed the classical Michaelis-Menten kinetics.", "contents": "Effects of melanin on tyrosine hydroxylase and phenylalanine hydroxylase. Melanin inhibited rat liver phenylalanine hydroxylase, but activated tyrosine hydroxylase from rat brain (caudate nucleus), rat adrenal glands, and bovine adrenal medulla. Activation of tyrosine hydroxylase by melanin was demonstrated with the extensively dialyzed enzyme and in suboptimal concentrations of the substrate (tyrosine) and the cofactor (6-methyltetrahydropterin). Tyrosine hydroxylase from rat brain was activated by melanin more markedly than that from rat adrenal glands. Purified and extensively dialyzed bovine adrenal tyrosine hydroxylase had two Km values with 6-methyltetrahydropterin, depending upon its concentrations, but the melanin-activated tyrosine hydroxylase had a single Km value and showed the classical Michaelis-Menten kinetics."}
{"id": "PMID:24475", "title": "Immobilized D-amino acid oxidase.", "content": "1. D-Amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating), EC 1.4.3.3) apoenzyme, holoenzyme and the enzyme-benzoate complex were active and stable when immobilized to aminoalkyl or carboxyalkyl agarose, or to cyanogen bromide-activated agarose. The immobilized enzyme-benzoate complex could be converted into the holo- and apoenzyme without being liberated from the agarose. 2. The apparent Michaelis constant and substrate specificity of the immobilized enzyme were similar to those of the free enzyme. The optimum pH of the reaction was shifted towards acidic side by 1.0-2.0 pH units from that of the free enzyme. 3. With increasing number of methylene groups of the 'spacer' from 3 to 5, molecular activity of the immobilized enzyme increased, while the apparent Miachaelis constant decreased.", "contents": "Immobilized D-amino acid oxidase. 1. D-Amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating), EC 1.4.3.3) apoenzyme, holoenzyme and the enzyme-benzoate complex were active and stable when immobilized to aminoalkyl or carboxyalkyl agarose, or to cyanogen bromide-activated agarose. The immobilized enzyme-benzoate complex could be converted into the holo- and apoenzyme without being liberated from the agarose. 2. The apparent Michaelis constant and substrate specificity of the immobilized enzyme were similar to those of the free enzyme. The optimum pH of the reaction was shifted towards acidic side by 1.0-2.0 pH units from that of the free enzyme. 3. With increasing number of methylene groups of the 'spacer' from 3 to 5, molecular activity of the immobilized enzyme increased, while the apparent Miachaelis constant decreased."}
{"id": "PMID:24477", "title": "The fate of extracellular glutathione in the rat.", "content": "When intravenously administered to rats, [U-14C]glycine-labelled GSSG, GSH and its analogue ophthalmic acid were rapidly removed from the blood. In perfusion studies with isolated liver, however, the compounds did not enter the liver tissue. Thus, uptake by this tissue is obviously not responsible for the removal of gamma-glutamyl tripeptides from the blood. Instead, rapid hydrolysis of the tripeptides was observed. The undegraded tripeptides were only detected in the blood immediately after administration. Within tissue the degradation product glycine accounted for all the radioactivity. After intravenous injection of the labelled tripeptides the radioactivity accumulated first in the kidney, as shown by autoradiographic studies and chemical analysis of different tissues. The hydrolysis of the gamma-glutamyl tripeptides decreased markedly after the renal arteries were clamped. These observations strongly suggest that renal tissue is the principal site of the degradation of the tripeptides. Inhibition studies and experiments with isolated renal tubules revealed that gamma-glutamyl transpeptidase catalyses the fast hydrolysis of the extracellular peptides. The results indicate that, when entering the extracellular space, glutathione and its analogues are completely hydrolysed and must be resynthesized after reuptake of the constituent amino acids. It is concluded that the degradation occurs mainly on the luminal surface of the renal brush-border membrane and that gamma-glutamyl transpeptidase is a glutathionase acting on extracellular glutathione.", "contents": "The fate of extracellular glutathione in the rat. When intravenously administered to rats, [U-14C]glycine-labelled GSSG, GSH and its analogue ophthalmic acid were rapidly removed from the blood. In perfusion studies with isolated liver, however, the compounds did not enter the liver tissue. Thus, uptake by this tissue is obviously not responsible for the removal of gamma-glutamyl tripeptides from the blood. Instead, rapid hydrolysis of the tripeptides was observed. The undegraded tripeptides were only detected in the blood immediately after administration. Within tissue the degradation product glycine accounted for all the radioactivity. After intravenous injection of the labelled tripeptides the radioactivity accumulated first in the kidney, as shown by autoradiographic studies and chemical analysis of different tissues. The hydrolysis of the gamma-glutamyl tripeptides decreased markedly after the renal arteries were clamped. These observations strongly suggest that renal tissue is the principal site of the degradation of the tripeptides. Inhibition studies and experiments with isolated renal tubules revealed that gamma-glutamyl transpeptidase catalyses the fast hydrolysis of the extracellular peptides. The results indicate that, when entering the extracellular space, glutathione and its analogues are completely hydrolysed and must be resynthesized after reuptake of the constituent amino acids. It is concluded that the degradation occurs mainly on the luminal surface of the renal brush-border membrane and that gamma-glutamyl transpeptidase is a glutathionase acting on extracellular glutathione."}
{"id": "PMID:24478", "title": "The dimerization of ferrihaems. I. The effect of buffer ions and specific cations on deuteroferrihaem dimerization.", "content": "The dimerization of dueteroferrihaem in aqueous solution has been investigated using a parameter, named the dimerization index (Robs). This is defined as the ratio of extinction coefficients at wavelengths corresponding to Soret band maxima for the monomeric and dimeric species, respectively. For solutions containing mainly monomeric species, Robs greater than 2, whereas for solutions containing mainly dimeric species Robs less than 1. A computer programme has been applied to determine values of the dimerization constant, K, defined as: K = [dimer] [H+]/[monomer]2. Phosphate buffer anions and Tris . HCl buffer enhanced dimerization. Monovalent and divalent cations also increased dimerization, but in a specific manner. The magnitudes of their effects increased in the order K+ less than Na+ less than Li+ less than Sr2+ less than Mg2+ approximately or equal to Ca2+. Values of K were determined for several concentrations of Na+ and Sr2+. These data are interpreted in terms of a stabilization of the ferrihaem dimer by the formation of ion triplets with the added cation 'sandwiched' between carboxyl residues of the adjacent ferrihaem monomeric units. General guidelines are recommended for the choice of conditions which minimize dimerization.", "contents": "The dimerization of ferrihaems. I. The effect of buffer ions and specific cations on deuteroferrihaem dimerization. The dimerization of dueteroferrihaem in aqueous solution has been investigated using a parameter, named the dimerization index (Robs). This is defined as the ratio of extinction coefficients at wavelengths corresponding to Soret band maxima for the monomeric and dimeric species, respectively. For solutions containing mainly monomeric species, Robs greater than 2, whereas for solutions containing mainly dimeric species Robs less than 1. A computer programme has been applied to determine values of the dimerization constant, K, defined as: K = [dimer] [H+]/[monomer]2. Phosphate buffer anions and Tris . HCl buffer enhanced dimerization. Monovalent and divalent cations also increased dimerization, but in a specific manner. The magnitudes of their effects increased in the order K+ less than Na+ less than Li+ less than Sr2+ less than Mg2+ approximately or equal to Ca2+. Values of K were determined for several concentrations of Na+ and Sr2+. These data are interpreted in terms of a stabilization of the ferrihaem dimer by the formation of ion triplets with the added cation 'sandwiched' between carboxyl residues of the adjacent ferrihaem monomeric units. General guidelines are recommended for the choice of conditions which minimize dimerization."}
{"id": "PMID:24479", "title": "The dimerization of ferrihaems. II. Equilibrium and kinetic studies of mesoferrihaem dimerization.", "content": "Spectrophotometric data have been determined for mesoferrihaem at several pH values and over a range of concentration covering four orders of magnitude. The data reveal a dimerization process according to the equation 2 monomer in equilibrium dimer + H+, analogous to earlier findings for deuteroferrihaem and protoferrihaem. The value of K (defined as K = [dimer] [H+]/[monomer]2) was found to be 6.92.10(-2). This is close to the value for deuteroferrihaem but much less than that for protoferrihaem. This is interpreted in terms of possible additional bonding between the delocalized electron systems in protoferrihaem dimers relative to those of mesoferrihaem and deuteroferrihaem. Rate constants for dimerization were determined by temperature-jump spectrophotometry. The pH dependence of the rate constants is explained in terms of two distinct pathways for the dimerization process. These involve either direct reaction between two undissociated monomer molecules or alternatively an initial acid dissociation of a monomer molecule followed by reaction between an undissociated and dissociated molecule.", "contents": "The dimerization of ferrihaems. II. Equilibrium and kinetic studies of mesoferrihaem dimerization. Spectrophotometric data have been determined for mesoferrihaem at several pH values and over a range of concentration covering four orders of magnitude. The data reveal a dimerization process according to the equation 2 monomer in equilibrium dimer + H+, analogous to earlier findings for deuteroferrihaem and protoferrihaem. The value of K (defined as K = [dimer] [H+]/[monomer]2) was found to be 6.92.10(-2). This is close to the value for deuteroferrihaem but much less than that for protoferrihaem. This is interpreted in terms of possible additional bonding between the delocalized electron systems in protoferrihaem dimers relative to those of mesoferrihaem and deuteroferrihaem. Rate constants for dimerization were determined by temperature-jump spectrophotometry. The pH dependence of the rate constants is explained in terms of two distinct pathways for the dimerization process. These involve either direct reaction between two undissociated monomer molecules or alternatively an initial acid dissociation of a monomer molecule followed by reaction between an undissociated and dissociated molecule."}
{"id": "PMID:24480", "title": "Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane.", "content": "Utilizing the spin-trapping agent phenyl-t-butyl nitrone, a free radical has been detected which is produced from carbon tetrachloride or bromotrichloromethane during the enzymic oxidation of NADPH by rat liver microsomes. The presence of NADPH is obligatory for generation of the radical. The formation of the trichloromethyl radical-phenyl-t-butyl nitrone adduct is an enzymic process, as evidenced by the inhibition of its formation in systems containing heated microsomes and in systems containing p-hydroxymercuribenzoate. A computer-simulated ESR spectrum for the trichloromethyl adduct of phenyl-t-butyl nitrone can reproduce the essential features of the spectrum of the spin-trapped radical produced enzymically from CCl4. A mechanism is proposed for the formation of the trichloromethyl radical from CCl4 or BrCCl3.", "contents": "Spin-trapping of the trichloromethyl radical produced during enzymic NADPH oxidation in the presence of carbon tetrachloride or bromotrichloromethane. Utilizing the spin-trapping agent phenyl-t-butyl nitrone, a free radical has been detected which is produced from carbon tetrachloride or bromotrichloromethane during the enzymic oxidation of NADPH by rat liver microsomes. The presence of NADPH is obligatory for generation of the radical. The formation of the trichloromethyl radical-phenyl-t-butyl nitrone adduct is an enzymic process, as evidenced by the inhibition of its formation in systems containing heated microsomes and in systems containing p-hydroxymercuribenzoate. A computer-simulated ESR spectrum for the trichloromethyl adduct of phenyl-t-butyl nitrone can reproduce the essential features of the spectrum of the spin-trapped radical produced enzymically from CCl4. A mechanism is proposed for the formation of the trichloromethyl radical from CCl4 or BrCCl3."}
{"id": "PMID:24482", "title": "Mass spectrometry of medicines. Quantitative determination by direct probe inlet system mass chromatography.", "content": "A fundamental study was performed to establish a method of quantitative analysis using mass chromatography by the direct inlet system. The samples were aspirin, phenacetin and caffeine, which are often used as cold medicines, and barbital, allobarbital, phenobarbital and phenytoin which are difficult to analyse by gas chromatography in their intact states. N-acetylsulfamine and ethyl p-aminobenzoate were used as internal standards. Direct inlet mass chromatography was performed by an on-line system of the Shimadzu LKB-9000 and the GC-MSPAC 300. The ratio of the cumulative ions of certain peaks of sample and the internal standard was studied. It was found that, whether the sample is a pure reagent or a mixture, the ratio of cumulative ions of a peak specific to the sample and of a selected peak of the internal standard is proportional to the sample size, the error being less than +/- 3.5% for aspirin, phenacetin and caffeine, and less than +/- 2.7% for barbital, allobarbital and phenobarbital. The same relationship was observed for the phenobarbital and phenytoin mixed in rat plasma, the error being less than +/- 2.0%. It can be concluded that this method is applicable to the quantiative determination of medicines in urine, body fluids and other biological samples.", "contents": "Mass spectrometry of medicines. Quantitative determination by direct probe inlet system mass chromatography. A fundamental study was performed to establish a method of quantitative analysis using mass chromatography by the direct inlet system. The samples were aspirin, phenacetin and caffeine, which are often used as cold medicines, and barbital, allobarbital, phenobarbital and phenytoin which are difficult to analyse by gas chromatography in their intact states. N-acetylsulfamine and ethyl p-aminobenzoate were used as internal standards. Direct inlet mass chromatography was performed by an on-line system of the Shimadzu LKB-9000 and the GC-MSPAC 300. The ratio of the cumulative ions of certain peaks of sample and the internal standard was studied. It was found that, whether the sample is a pure reagent or a mixture, the ratio of cumulative ions of a peak specific to the sample and of a selected peak of the internal standard is proportional to the sample size, the error being less than +/- 3.5% for aspirin, phenacetin and caffeine, and less than +/- 2.7% for barbital, allobarbital and phenobarbital. The same relationship was observed for the phenobarbital and phenytoin mixed in rat plasma, the error being less than +/- 2.0%. It can be concluded that this method is applicable to the quantiative determination of medicines in urine, body fluids and other biological samples."}
{"id": "PMID:24483", "title": "Continuous production of NADP by immobilized Achromobacter aceris cells.", "content": "Several microorganisms having higher nicotinamide adenine dinucleotide kinase (NAD kinase, EC 2.7.1.23) activity were immobilized into polyacrylamide gel lattices. The enzyme activity field by immobilization was highest in Achromobacter aceris AKU 0120. By the incubation of the immobilized A. aceris cells at pH 4.0, the NAD kinase activity increased and the adenosine triphosphate (ATP)-degradation activity disappeared completely. Enzymatic properties of the immobilized A. aceris cells were investigated and compared with those of intact cells. The optimal pH and the optimal temperature of immobilized cells were the same as those of intact cells. Immobilized cell NAD kinase was more stable than that of intact cells. The operational half-life of immobilized cells was 20 days when the substrate solution was passed through a column packed with immobilized cells at a flow rate which gives a space velocity (SV) of 0.1 hr-1 at 37 degrees C. On the other hand, the half-life of the intact cells was only 6 hr.", "contents": "Continuous production of NADP by immobilized Achromobacter aceris cells. Several microorganisms having higher nicotinamide adenine dinucleotide kinase (NAD kinase, EC 2.7.1.23) activity were immobilized into polyacrylamide gel lattices. The enzyme activity field by immobilization was highest in Achromobacter aceris AKU 0120. By the incubation of the immobilized A. aceris cells at pH 4.0, the NAD kinase activity increased and the adenosine triphosphate (ATP)-degradation activity disappeared completely. Enzymatic properties of the immobilized A. aceris cells were investigated and compared with those of intact cells. The optimal pH and the optimal temperature of immobilized cells were the same as those of intact cells. Immobilized cell NAD kinase was more stable than that of intact cells. The operational half-life of immobilized cells was 20 days when the substrate solution was passed through a column packed with immobilized cells at a flow rate which gives a space velocity (SV) of 0.1 hr-1 at 37 degrees C. On the other hand, the half-life of the intact cells was only 6 hr."}
{"id": "PMID:24484", "title": "Mathematical modeling of lag phases in microbial growth.", "content": "This paper describes a mathematical method of the lap phases of Saccharomyces cerevisiae that incorporates the basic concepts previously presented in a two-stage deterministic model for the growth of this organism under conditions of oxygen excess with a sugar as the growth-limiting substrate. The model structure was suggested by an extensive investigation of the causes of the lap phases of S. cerevisiae which found that, in contrast to the traditionally accepted trends, the length of the lap phase was not inoculum-size dependent. This was consistent with other previously published work which suggested that a major factor in the length of the lag phases in S. cerevisiae was the need to synthesize adequate levels of glycolytic and respiratory enzymes. These suggestions were confirmed experimentally with lag-age data. Based on this conclusion a mathematical model was developed incorporating a description of the levels of glycolytic and respiratory enzymes and their effect on the growth rate and metabolism. This model was tested experimentally and the initial results indicate that many aspects of the lag phase of this organism may be described mathematically. The experimental findings further support the concept of primary regulatory control proposed by Bijkerk and Hall.", "contents": "Mathematical modeling of lag phases in microbial growth. This paper describes a mathematical method of the lap phases of Saccharomyces cerevisiae that incorporates the basic concepts previously presented in a two-stage deterministic model for the growth of this organism under conditions of oxygen excess with a sugar as the growth-limiting substrate. The model structure was suggested by an extensive investigation of the causes of the lap phases of S. cerevisiae which found that, in contrast to the traditionally accepted trends, the length of the lap phase was not inoculum-size dependent. This was consistent with other previously published work which suggested that a major factor in the length of the lag phases in S. cerevisiae was the need to synthesize adequate levels of glycolytic and respiratory enzymes. These suggestions were confirmed experimentally with lag-age data. Based on this conclusion a mathematical model was developed incorporating a description of the levels of glycolytic and respiratory enzymes and their effect on the growth rate and metabolism. This model was tested experimentally and the initial results indicate that many aspects of the lag phase of this organism may be described mathematically. The experimental findings further support the concept of primary regulatory control proposed by Bijkerk and Hall."}
{"id": "PMID:24487", "title": "[Effect of narcotic analgesics on excitatory transmission in the spinal cord].", "content": "As demonstrated on nonanesthetized curare-immobilized spinal cats morphine, promedol and fentanyl failed to alter the amplitude of induced potentials in the ventro-lateral columns of the lumbar spinal cord, evoked by a single or repetitive stimulation of the cutaneous or pelvic nerves. In some experiments the same drugs inhibited the nerurons of the posterior horns of the spinal cord activated by the nociceptive stimulation of the peripheral receptors in intraarterial administration of bradykinin. It is suggested that a spinal component was involved in the action of hypnotic analgetics.", "contents": "[Effect of narcotic analgesics on excitatory transmission in the spinal cord]. As demonstrated on nonanesthetized curare-immobilized spinal cats morphine, promedol and fentanyl failed to alter the amplitude of induced potentials in the ventro-lateral columns of the lumbar spinal cord, evoked by a single or repetitive stimulation of the cutaneous or pelvic nerves. In some experiments the same drugs inhibited the nerurons of the posterior horns of the spinal cord activated by the nociceptive stimulation of the peripheral receptors in intraarterial administration of bradykinin. It is suggested that a spinal component was involved in the action of hypnotic analgetics."}
{"id": "PMID:24489", "title": "Exertion injuries in adolescent athletes.", "content": "A series of 147 cases of exertion injuries in less than or equal to 15 years old athletes is presented. All injuries occurred during training or athletic performances without trauma and caused symptoms that prevented athletic exercises. There were 67 girls (46%) and 80 boys (54%) in the material. About 90% of them had been training for more than one year before the onset of the symptoms; 65% were interested in track and field athletics, 13% in ball games, 11% in skiing, 4% in swimming, and 3% in orienteering. The rest were interested in other sports. About 33% of the injuries were growth disturbances or osteochondroses seen also in other children. About 15% were anomalies, deformities or earlier osteochondritic changes, which caused first symptoms during the physical exercise; 50% were typical overuse injuries that may bother adult athletes, too; 43% of the injuries were localized in ankle, foot and heel, 31% in knee, 8% in back and trunk, 7% in pelvic and hip region, and the rest in other parts of the body. The injuries were generally slight, no permanent disability was noticed. Rest and conservation therapy cured most cases; operative treatment was used in only eight cases.", "contents": "Exertion injuries in adolescent athletes. A series of 147 cases of exertion injuries in less than or equal to 15 years old athletes is presented. All injuries occurred during training or athletic performances without trauma and caused symptoms that prevented athletic exercises. There were 67 girls (46%) and 80 boys (54%) in the material. About 90% of them had been training for more than one year before the onset of the symptoms; 65% were interested in track and field athletics, 13% in ball games, 11% in skiing, 4% in swimming, and 3% in orienteering. The rest were interested in other sports. About 33% of the injuries were growth disturbances or osteochondroses seen also in other children. About 15% were anomalies, deformities or earlier osteochondritic changes, which caused first symptoms during the physical exercise; 50% were typical overuse injuries that may bother adult athletes, too; 43% of the injuries were localized in ankle, foot and heel, 31% in knee, 8% in back and trunk, 7% in pelvic and hip region, and the rest in other parts of the body. The injuries were generally slight, no permanent disability was noticed. Rest and conservation therapy cured most cases; operative treatment was used in only eight cases."}
{"id": "PMID:24490", "title": "Perfusion characteristics of preserved canine kidneys subjected to warm ischaemia.", "content": "Canine kidneys were subjected to 0, 15 or 30 min of warm ischaemia followed by 24 hours preservation by perfusion. Changes in perfusate concentration of acid radicles, lactate, free fatty acid and lactice dehydrogenase were assessed at 1 hour and 24 hours. With the exception of LDH concentration at 1 hour, no single parameter was capable of detecting kidneys which were so damaged as to be non-life supporting.", "contents": "Perfusion characteristics of preserved canine kidneys subjected to warm ischaemia. Canine kidneys were subjected to 0, 15 or 30 min of warm ischaemia followed by 24 hours preservation by perfusion. Changes in perfusate concentration of acid radicles, lactate, free fatty acid and lactice dehydrogenase were assessed at 1 hour and 24 hours. With the exception of LDH concentration at 1 hour, no single parameter was capable of detecting kidneys which were so damaged as to be non-life supporting."}
{"id": "PMID:24493", "title": "Effect of concanavalin A on black widow spider venom activity at the neuromuscular junction: implications for mechanisms of venom action.", "content": "Concanavalin A (Con A) inhibits black widow spider venom-induced transmitter release at both tissue-cultured and adult neuromuscular junctions and also inhibits the venom-induced destruction of cultured neurites. This inhibitory action is partially or completely prevented by prior treatment with colchicine. Neither colchicine nor Con A interacts significantly with depolarization-induced transmitter release. These results are analogous to those obtained from experiments on lymphocyte surface receptor capping. They suggest that redistribution of neuronal membrane components may be a crucial step in spider venom action. This membrane redistribution appears to be modulated in neurons, as in other cell types, by microtubule-microfilament array. How such a redistribution causes increased transmitter release cannot as yet be specified. Changes in the ionic permeability of sodium and potassium were examined as likely mechanisms. Increased sodium influx (and seondary release of calcium from intracellular stores) cannot be the basis for spider venom action. Increased potassium efflux remains a possibility, but is not consistent with all of the data. Other possible mechanisms are also suggested.", "contents": "Effect of concanavalin A on black widow spider venom activity at the neuromuscular junction: implications for mechanisms of venom action. Concanavalin A (Con A) inhibits black widow spider venom-induced transmitter release at both tissue-cultured and adult neuromuscular junctions and also inhibits the venom-induced destruction of cultured neurites. This inhibitory action is partially or completely prevented by prior treatment with colchicine. Neither colchicine nor Con A interacts significantly with depolarization-induced transmitter release. These results are analogous to those obtained from experiments on lymphocyte surface receptor capping. They suggest that redistribution of neuronal membrane components may be a crucial step in spider venom action. This membrane redistribution appears to be modulated in neurons, as in other cell types, by microtubule-microfilament array. How such a redistribution causes increased transmitter release cannot as yet be specified. Changes in the ionic permeability of sodium and potassium were examined as likely mechanisms. Increased sodium influx (and seondary release of calcium from intracellular stores) cannot be the basis for spider venom action. Increased potassium efflux remains a possibility, but is not consistent with all of the data. Other possible mechanisms are also suggested."}
{"id": "PMID:24498", "title": "Quantitative electron miscroscopic studies on the kinetics of secretory granules in G-cells.", "content": "Ultrastructural studies of secretory granules of rat antral G-cells and measurement of serum gastrin level were performed under the condition of fasting and administration of alkaline solution into the stomach. On electron micrographs, no qualitative difference was observed among those experimental groups. However, morphometrical analysis revealed significant quantitative differences. The population density of secretory granules of the rats treated once with alkali first increased and then decreased reaching that of the fasted group, while that of the repeatedly treated group remained nearly equal to the maximum value. The average sectioned surface area of secretory granules tended to decrease for 1.5 h after the stimulation but the differences was not significant among those groups. From the results obtained at present, responding to chemical stimulation such as pH changes in the antrum, it seems probable that not only exocytosis but also migration of secretory granules from supra- and/or para-nuclear portion to the basal portion of the cell occurs rapidly in G-cells and that both these processes are inhibited immediately by antral acidification. Moreover, the present results apparently indicate that under the condition of no antral acidification G-cells have a capacity of secreting gastrin for a fairly long time, such as 4--8 h, responding to adequate stimulus. These findings are strongly suggestive of the existence of a capacious pool of granules in the supra- and/or para-nuclear cytoplasm or of fairly speedy production of secretory granules in the Golgi area.", "contents": "Quantitative electron miscroscopic studies on the kinetics of secretory granules in G-cells. Ultrastructural studies of secretory granules of rat antral G-cells and measurement of serum gastrin level were performed under the condition of fasting and administration of alkaline solution into the stomach. On electron micrographs, no qualitative difference was observed among those experimental groups. However, morphometrical analysis revealed significant quantitative differences. The population density of secretory granules of the rats treated once with alkali first increased and then decreased reaching that of the fasted group, while that of the repeatedly treated group remained nearly equal to the maximum value. The average sectioned surface area of secretory granules tended to decrease for 1.5 h after the stimulation but the differences was not significant among those groups. From the results obtained at present, responding to chemical stimulation such as pH changes in the antrum, it seems probable that not only exocytosis but also migration of secretory granules from supra- and/or para-nuclear portion to the basal portion of the cell occurs rapidly in G-cells and that both these processes are inhibited immediately by antral acidification. Moreover, the present results apparently indicate that under the condition of no antral acidification G-cells have a capacity of secreting gastrin for a fairly long time, such as 4--8 h, responding to adequate stimulus. These findings are strongly suggestive of the existence of a capacious pool of granules in the supra- and/or para-nuclear cytoplasm or of fairly speedy production of secretory granules in the Golgi area."}
{"id": "PMID:24499", "title": "Relaxin, a male hormone? Immunocytological localization of a related antigen in the boar testis.", "content": "Convincingly demonstrated by immunocytological methods in females of several mammalian species, relaxin has not yet been localized in the male. Immunocytologically, a related antigen was identified in adult normal boar testes using and anti- [NIH P-relaxin/HSA] antiserum free of anti HSA Abs. A strong reaction was observed in interstitial cells, a weaker but very clear one in Sertoli cells. NIH P-relaxin and HC1-acetone extracts of either corpora lutea from pregnant sows or boar testes inhibited the immunofluorescence of the reactive structures in the boar testes as well as in ovaries of pregnant sows. Ethanol-acetone precipitates from boar rete testis or caudal epididymal fluids inhibited the reaction of interstitial and Sertoli cells, but this inhibition in the sow was limited only to degenerative ovarian structures, probably due to an insufficient level of inhibiting antigen in these two seminal fluids, in contrast with the very high concentration of relaxin in luteal cells of pregnant sows. Specific immunofluorescence was observed neither in ectopic testes of adult monocryptorchid boars (contrary to scrotal testes in these same animals) nor in testes of prepuberal pigs. The specificity and meaning of these results are discussed.", "contents": "Relaxin, a male hormone? Immunocytological localization of a related antigen in the boar testis. Convincingly demonstrated by immunocytological methods in females of several mammalian species, relaxin has not yet been localized in the male. Immunocytologically, a related antigen was identified in adult normal boar testes using and anti- [NIH P-relaxin/HSA] antiserum free of anti HSA Abs. A strong reaction was observed in interstitial cells, a weaker but very clear one in Sertoli cells. NIH P-relaxin and HC1-acetone extracts of either corpora lutea from pregnant sows or boar testes inhibited the immunofluorescence of the reactive structures in the boar testes as well as in ovaries of pregnant sows. Ethanol-acetone precipitates from boar rete testis or caudal epididymal fluids inhibited the reaction of interstitial and Sertoli cells, but this inhibition in the sow was limited only to degenerative ovarian structures, probably due to an insufficient level of inhibiting antigen in these two seminal fluids, in contrast with the very high concentration of relaxin in luteal cells of pregnant sows. Specific immunofluorescence was observed neither in ectopic testes of adult monocryptorchid boars (contrary to scrotal testes in these same animals) nor in testes of prepuberal pigs. The specificity and meaning of these results are discussed."}
{"id": "PMID:24501", "title": "In vitro studies on the effects on granular gland secretion in Xenopus laevis skin of stimulation and blockade of alpha and beta adrenoceptors of myoepithelial cells.", "content": "Secretion from the granular glands of Xenopus laevis skin was stimulated by alpha-adrenergic agonists, an effect which was blocked by alpha-adrenergic antagonists and inhibited by beta-adrenergic agonists, db-cAMP and diazoxide. The inhibition by isoprenaline and salbutamol, but not that by diazoxide, was blocked by a beta-adrenergic antagonist. It is concluded that the myoepithelial cells surrounding the secretory compartment of the granular glands bear alpha and beta adrenoceptors, and that the beta receptors comprise, or at least include beta2 receptors.", "contents": "In vitro studies on the effects on granular gland secretion in Xenopus laevis skin of stimulation and blockade of alpha and beta adrenoceptors of myoepithelial cells. Secretion from the granular glands of Xenopus laevis skin was stimulated by alpha-adrenergic agonists, an effect which was blocked by alpha-adrenergic antagonists and inhibited by beta-adrenergic agonists, db-cAMP and diazoxide. The inhibition by isoprenaline and salbutamol, but not that by diazoxide, was blocked by a beta-adrenergic antagonist. It is concluded that the myoepithelial cells surrounding the secretory compartment of the granular glands bear alpha and beta adrenoceptors, and that the beta receptors comprise, or at least include beta2 receptors."}
{"id": "PMID:24503", "title": "The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I. Activation through conjugation with glutathion in vitro.", "content": "One of the main components in the waste products from vinyl chloride industries (EDC-tar), is ethylene dichloride (1,2-dichloroethane). This compound has been tested for mutagenicity on Salmonella typhimurium TA 1535. It is concluded that 1,2-dichloroethane gives a weak direct mutagenic effect, which is enhanced by addition of the postmitochondrial liver fraction (S-9). This activation is NADPH-independent and non microsomal. It is caused by a factor in the soluble fraction (115 000 g supernatant). This activation was further enhanced by the addition of glutathione but not by the addition of L-cysteine, N-acetyl-L-cysteine or 2-mercaptoethanol. No activation was observed when glutathione was added in the presence of a totally denaturated S-9 fraction or in the absence of this fraction. Activation of 1,2-dichloroethane was also found in the presence of glutathione and glutathione S-transferase A and C but not with glutathione S-tranferase B. A synthetic conjugate S-(2-chloroethyl)-L-cysteine gave a strong direct mutagenic effect at concentrations where no effects were seen with 1,2-dichloroethane. It is thus concluded that 1,2-dichloroethane is activated by conjugation to glutathione. Another main component in EDC-tar, 1,1,2-trichloroethane, was not mutagenic under any of our experimental conditions. For comparison 1,2-dibromoethane was also tested and gave a stronger direct mutagenic effect than 1,2-dichloroethane. Like the latter 1,2-dibromoethane was also activated by a NADPH-independent process.", "contents": "The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I. Activation through conjugation with glutathion in vitro. One of the main components in the waste products from vinyl chloride industries (EDC-tar), is ethylene dichloride (1,2-dichloroethane). This compound has been tested for mutagenicity on Salmonella typhimurium TA 1535. It is concluded that 1,2-dichloroethane gives a weak direct mutagenic effect, which is enhanced by addition of the postmitochondrial liver fraction (S-9). This activation is NADPH-independent and non microsomal. It is caused by a factor in the soluble fraction (115 000 g supernatant). This activation was further enhanced by the addition of glutathione but not by the addition of L-cysteine, N-acetyl-L-cysteine or 2-mercaptoethanol. No activation was observed when glutathione was added in the presence of a totally denaturated S-9 fraction or in the absence of this fraction. Activation of 1,2-dichloroethane was also found in the presence of glutathione and glutathione S-transferase A and C but not with glutathione S-tranferase B. A synthetic conjugate S-(2-chloroethyl)-L-cysteine gave a strong direct mutagenic effect at concentrations where no effects were seen with 1,2-dichloroethane. It is thus concluded that 1,2-dichloroethane is activated by conjugation to glutathione. Another main component in EDC-tar, 1,1,2-trichloroethane, was not mutagenic under any of our experimental conditions. For comparison 1,2-dibromoethane was also tested and gave a stronger direct mutagenic effect than 1,2-dichloroethane. Like the latter 1,2-dibromoethane was also activated by a NADPH-independent process."}
{"id": "PMID:24505", "title": "Neurogenic vasodilation of cat cerebral arteries.", "content": "Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, gamma-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response.", "contents": "Neurogenic vasodilation of cat cerebral arteries. Transmural nerve stimulation (TNS) with 0.3-msec pulses between 1 and 25 Hz dilated cat cerebral artery segments in the presence of active muscle tone. Maximum vasodilatation occurred at 8 Hz. The dilator response to exogenous acetylcholine, but not to TNS, was abolished by atropine. Neither physostigmine nor hemicholinium affected the dilator response to TNS, which persisted after administration of guanethidine, phenoxybenzamine, propranolol, reserpine, and chronic sympathectomy. However, it was abolished by tetrodotoxin and cold storage. When examined histochemically, cat and rabbit cerebral arteries exhibited a rich plexiform distribution of acetylcholinesterase which was not affected appreciably by sympathetic denervation. These results suggest that vasodilation is not mediated through modification of sympathetic activity. They also indicate the existence of a nonadrenergic, possibly noncholinergic, vasodilator innervation in cat cerebral arteries. Preliminary studies suggest that the transmitter is not histamine, ATP, prostaglandins, gamma-aminobutyric acid, dopamine, or serotonin. The cat cerebral artery segments contrast with the isolated rabbit cerebral arteries which predominantly constrict in response to TNS and show a small dilator response."}
{"id": "PMID:24506", "title": "An investigation of factors influencing the measurement of creatine phosphokinase activity in serum using coupled enzymatic methods.", "content": "1. The factors influencing the measurement of creatine phosphokinase (CPK) activity in serum by coupled enzymatic methods were investigated to establish optimum conditions for this type of assay. Such a study was indicated following observations by the authors of poor performance of commerically produced reagent kits together with the failure of most of the established an well accepted methods to operate under true optimum zero order kinetics in the reaction phase state. 2. The factors invested were the effects of pH, substrate concentrations (creatine phosphate, glucose and NADP+), added auxiliary (hexokinase) and indicator (glucose-6-phosphate dehydrogenase) enzymes, dithiothreitol (DTT) as an activator and conditions of storage of substrate stability. DTT was found to be a suitable activator but not a reactivator of the reaction. The optimum concentrations of creatine phosphate, glucose and NADP+ were found to be 20.0, 20.0 and 2.0 mmol/litre, respectively. Optimum activieies of the enzymes, glucose-6-phosphate dehydrosenase and hexokinase were 1000 and 2000 units/litre, respectively. 3. The between-day precision of the method for measuring serum at pH 6.8 and 30 degrees C at three activity levels under the optimum conditions developed was excellent yielding coefficients of variation ranging from 2.0 to 2.7%.", "contents": "An investigation of factors influencing the measurement of creatine phosphokinase activity in serum using coupled enzymatic methods. 1. The factors influencing the measurement of creatine phosphokinase (CPK) activity in serum by coupled enzymatic methods were investigated to establish optimum conditions for this type of assay. Such a study was indicated following observations by the authors of poor performance of commerically produced reagent kits together with the failure of most of the established an well accepted methods to operate under true optimum zero order kinetics in the reaction phase state. 2. The factors invested were the effects of pH, substrate concentrations (creatine phosphate, glucose and NADP+), added auxiliary (hexokinase) and indicator (glucose-6-phosphate dehydrogenase) enzymes, dithiothreitol (DTT) as an activator and conditions of storage of substrate stability. DTT was found to be a suitable activator but not a reactivator of the reaction. The optimum concentrations of creatine phosphate, glucose and NADP+ were found to be 20.0, 20.0 and 2.0 mmol/litre, respectively. Optimum activieies of the enzymes, glucose-6-phosphate dehydrosenase and hexokinase were 1000 and 2000 units/litre, respectively. 3. The between-day precision of the method for measuring serum at pH 6.8 and 30 degrees C at three activity levels under the optimum conditions developed was excellent yielding coefficients of variation ranging from 2.0 to 2.7%."}
{"id": "PMID:24507", "title": "Improved method for fractionating gamma-glutamyltransferase by electrophoresis on cellulose acetate.", "content": "I describe a method of fractionating gamma-glutamyltransferase on cellulose acetate. The tracing is obtained in parallel with that of serum protein, and the gamma-glutamyltransferase bands are characterized by correspondence with the major protein fractions. The overall pattern of the isoenzyme activity in normal sera is one of activity in the alpha1- and alpha2-globulin regions. In hepatic diseases four bands are usually present, but some more specific observations are possible, e.g., the presence of an intense beta-globulin band in occlusive icterus, intra- or extrahepatic, and a marked alpha2-globulin band in alcoholism. The potentialities of this technique as a diagnostic and prognostic aid together with its simplicity prompt me to recommend its use in the clinical laboratory.", "contents": "Improved method for fractionating gamma-glutamyltransferase by electrophoresis on cellulose acetate. I describe a method of fractionating gamma-glutamyltransferase on cellulose acetate. The tracing is obtained in parallel with that of serum protein, and the gamma-glutamyltransferase bands are characterized by correspondence with the major protein fractions. The overall pattern of the isoenzyme activity in normal sera is one of activity in the alpha1- and alpha2-globulin regions. In hepatic diseases four bands are usually present, but some more specific observations are possible, e.g., the presence of an intense beta-globulin band in occlusive icterus, intra- or extrahepatic, and a marked alpha2-globulin band in alcoholism. The potentialities of this technique as a diagnostic and prognostic aid together with its simplicity prompt me to recommend its use in the clinical laboratory."}
{"id": "PMID:24512", "title": "Correlation between plasma diphenhydramine level and sedative and antihistamine effects.", "content": "The sedative and antihistamine effects of diphenhydramine were assessed in relation to plasma concentration after placebo, diphenhydramine 50 mg intravenously, and diphenhydramine 50 mg orally to each of 6 healthy volunteers on three separate occasions. Diphenhydramine plasma elimination t1/2 was 3.0 to 4.3 hr, volume of distribution was 188 to 336 L, and clearance was 637 to 1,014 ml/min. Systemic bioavailability of the oral preparation ranged from 0.26 to 0.60. The sedative effect of intravenous diphenhydramine differed from that of placebo only during the first 3 hr. Antihistamine effect, as measured by reduction of histamine provoked skin wheal diameter, was significantly different from that of placebo for at least 8 hr. There was a positive correlation between plasma diphenhydramine level and sedative and antihistamine effects, but wide variation in the extent and rate of change of these effects were observed between the subject. There appears to be a concentration range of 25 to 50 ng/ml, within which there is significant antihistamine effect without significant sedation.", "contents": "Correlation between plasma diphenhydramine level and sedative and antihistamine effects. The sedative and antihistamine effects of diphenhydramine were assessed in relation to plasma concentration after placebo, diphenhydramine 50 mg intravenously, and diphenhydramine 50 mg orally to each of 6 healthy volunteers on three separate occasions. Diphenhydramine plasma elimination t1/2 was 3.0 to 4.3 hr, volume of distribution was 188 to 336 L, and clearance was 637 to 1,014 ml/min. Systemic bioavailability of the oral preparation ranged from 0.26 to 0.60. The sedative effect of intravenous diphenhydramine differed from that of placebo only during the first 3 hr. Antihistamine effect, as measured by reduction of histamine provoked skin wheal diameter, was significantly different from that of placebo for at least 8 hr. There was a positive correlation between plasma diphenhydramine level and sedative and antihistamine effects, but wide variation in the extent and rate of change of these effects were observed between the subject. There appears to be a concentration range of 25 to 50 ng/ml, within which there is significant antihistamine effect without significant sedation."}
{"id": "PMID:24510", "title": "Psychological aspects of chronic pain.", "content": "Except in emergencies, the physician's obligation is not to relieve pain, but to diagnose and treat pathology. Psychological factors complicate organic pain, and make the diagnosis of \"psychogenic\" pain virtually impossible on the basis of psychological tests alone. In acute (short-term) pain, anti-anxiety agents are useful, but in chronic pain antidepressants are usually more appropriate. Continuing anxiolytic drugs past the acute stage tends to potentiate depressions. In addition to antidepressants, modalities which help in the management of chronic pain are physical therapy, transcutaneous electrical neurostimulation, use of weak analgesics on a \"clock\" rather than an \"as needed\" basis, and behavior modification. Explicit agreement on the features of the doctor--patient relationship is almost always essential for successfully managing these difficult and demanding patients.", "contents": "Psychological aspects of chronic pain. Except in emergencies, the physician's obligation is not to relieve pain, but to diagnose and treat pathology. Psychological factors complicate organic pain, and make the diagnosis of \"psychogenic\" pain virtually impossible on the basis of psychological tests alone. In acute (short-term) pain, anti-anxiety agents are useful, but in chronic pain antidepressants are usually more appropriate. Continuing anxiolytic drugs past the acute stage tends to potentiate depressions. In addition to antidepressants, modalities which help in the management of chronic pain are physical therapy, transcutaneous electrical neurostimulation, use of weak analgesics on a \"clock\" rather than an \"as needed\" basis, and behavior modification. Explicit agreement on the features of the doctor--patient relationship is almost always essential for successfully managing these difficult and demanding patients."}
{"id": "PMID:24527", "title": "Some clinical aspects of caprine reproduction.", "content": "Several clinical reproductive problems in the female dairy goat are considered, including estrus detection, artificial insemination, pregnancy diagnosis, abortions, and periparturient difficulties. Sexual behavior of the buck, onset of puberty, techniques for semen collection and evaluation, the production of teaser animals, and methods of castration are also discussed. Recognition of the intersex goat, which may have a masculine, feminine, or intermediate phenotype, is necessary in herds where naturally polled animals are bred.", "contents": "Some clinical aspects of caprine reproduction. Several clinical reproductive problems in the female dairy goat are considered, including estrus detection, artificial insemination, pregnancy diagnosis, abortions, and periparturient difficulties. Sexual behavior of the buck, onset of puberty, techniques for semen collection and evaluation, the production of teaser animals, and methods of castration are also discussed. Recognition of the intersex goat, which may have a masculine, feminine, or intermediate phenotype, is necessary in herds where naturally polled animals are bred."}
{"id": "PMID:24528", "title": "The effects of obstetrical medication on the behavior of Israeli newborn infants and some comparisons with Uruguayan and American infants.", "content": "The effects of obstetrical medication on neonatal behavior were studied using a sample of Israeli infants from medicated and nonmedicated mothers. Few significant behavioral differences were detected in the first month of life, and there was no difference in Bayley Infant Scale performance at 3 months of age. Comparative analyses using samples of American and Uruguayan infants and additional data from other studies of American newborns led to the conclusion that light levels of obstetrical medication do not appear to have significant effects on neonatal behavior. However, this may well be qualified by some initial population differences, by the measurements commonly used in the studies reviewed, and possibly by critical cutoff points dividing the levels of medication that will and will not affect neonatal behavior.", "contents": "The effects of obstetrical medication on the behavior of Israeli newborn infants and some comparisons with Uruguayan and American infants. The effects of obstetrical medication on neonatal behavior were studied using a sample of Israeli infants from medicated and nonmedicated mothers. Few significant behavioral differences were detected in the first month of life, and there was no difference in Bayley Infant Scale performance at 3 months of age. Comparative analyses using samples of American and Uruguayan infants and additional data from other studies of American newborns led to the conclusion that light levels of obstetrical medication do not appear to have significant effects on neonatal behavior. However, this may well be qualified by some initial population differences, by the measurements commonly used in the studies reviewed, and possibly by critical cutoff points dividing the levels of medication that will and will not affect neonatal behavior."}
{"id": "PMID:24529", "title": "Implications of disorders of purine metabolism for the kidney and the urinary tract.", "content": "The spectrum of kidney and urinary tract disorders related to purines comprises acute hyperuricosuric nephropathy, chronic urate nephropathy and urolithiasis. Two factors in the development of acute hyperuricosuric nephropathy are increased uric acid concentration and low pH in the tubular fluid. Chronic urate nephropathy still possess several problems: incidence (although this seems to be decreasing, presumably owing to effective prevention), the source of interstitial urate, the cause of the interstitial deposition of urate, and the role of urate deposits in the pathogenesis of the interstitial nephropathy. The relation of the experimental nephropathy to the pathogenesis of chronic urate nephropathy in the human is not yet clear but a model is proposed according to which interstitial urate derives from two sources: hyperuricaemic plasma and hyperuricosuric tubular fluid. Urolithiasis related to purines leads to uric acid-urate stones, xanthine stones, 2,8-dihydroxyadenine stones, iatrogenic xanthine and oxipurinol stones, and possibly calcium stones. Pathogenetic factors in uric acid lithiasis are hyperuricosuria (whether due to an inborn enzyme abnormality or of unknown aetiology) and low urinary pH; oliguria is a contributory factor. There remain several open questions about uric acid lithiasis: incidence, the shift of its location from lower to upper urinary tract, the interplay of pathogenetic factors, and the role of compounds which inhibit crystallization.", "contents": "Implications of disorders of purine metabolism for the kidney and the urinary tract. The spectrum of kidney and urinary tract disorders related to purines comprises acute hyperuricosuric nephropathy, chronic urate nephropathy and urolithiasis. Two factors in the development of acute hyperuricosuric nephropathy are increased uric acid concentration and low pH in the tubular fluid. Chronic urate nephropathy still possess several problems: incidence (although this seems to be decreasing, presumably owing to effective prevention), the source of interstitial urate, the cause of the interstitial deposition of urate, and the role of urate deposits in the pathogenesis of the interstitial nephropathy. The relation of the experimental nephropathy to the pathogenesis of chronic urate nephropathy in the human is not yet clear but a model is proposed according to which interstitial urate derives from two sources: hyperuricaemic plasma and hyperuricosuric tubular fluid. Urolithiasis related to purines leads to uric acid-urate stones, xanthine stones, 2,8-dihydroxyadenine stones, iatrogenic xanthine and oxipurinol stones, and possibly calcium stones. Pathogenetic factors in uric acid lithiasis are hyperuricosuria (whether due to an inborn enzyme abnormality or of unknown aetiology) and low urinary pH; oliguria is a contributory factor. There remain several open questions about uric acid lithiasis: incidence, the shift of its location from lower to upper urinary tract, the interplay of pathogenetic factors, and the role of compounds which inhibit crystallization."}
{"id": "PMID:24530", "title": "Characterization of human adenosine deaminase.", "content": "A deficiency of adenosine deaminase in man is associated with one form of severe combined immunodeficiency disease. In an attempt to define the nature of this relationship we have characterized the normal human enzyme and examined the role of this enzyme in monocyte-macrophage activation. The human enzyme was purified 800 000-fold to apparent homogeneity from human erythrocytes with 31% recovery by immunoabsorbent chromatography. The homogeneous protein contains carbohydrate and has a subunit molecular weight of 42 000, estimated by sodium dodecyl sulphate gel electrophoresis. The enzyme was found to exist in either a soluble or a particulate form. The active soluble forms are interconvertible with apparent molecular weights of 36 000 (small), 114 000 (intermediate), and 298 000 (large). However, conversion of the small form into the large form needs a protein with a molecular weight of 200 000 which has no adenosine deaminase activity.", "contents": "Characterization of human adenosine deaminase. A deficiency of adenosine deaminase in man is associated with one form of severe combined immunodeficiency disease. In an attempt to define the nature of this relationship we have characterized the normal human enzyme and examined the role of this enzyme in monocyte-macrophage activation. The human enzyme was purified 800 000-fold to apparent homogeneity from human erythrocytes with 31% recovery by immunoabsorbent chromatography. The homogeneous protein contains carbohydrate and has a subunit molecular weight of 42 000, estimated by sodium dodecyl sulphate gel electrophoresis. The enzyme was found to exist in either a soluble or a particulate form. The active soluble forms are interconvertible with apparent molecular weights of 36 000 (small), 114 000 (intermediate), and 298 000 (large). However, conversion of the small form into the large form needs a protein with a molecular weight of 200 000 which has no adenosine deaminase activity."}
{"id": "PMID:24531", "title": "The purinergic nerve hypothesis.", "content": "Experiments over the past decade have revealed a third component in the autonomic nervous system which is neither adrenergic nor cholinergic. These nerves are strongly represented in the gastrointestinal tract of a wide range of vertebrate species and have also been identified in lung, trachea, retractor penis, bladder, oesophagus, eye, seminal vesicle and in some parts of the cardiovascular system and brain. Evidence has been presented that the principal active substance released by these nerves in the gut is a purine nucleotide, probably ATP, and they have therefore been termed 'purinergic'. The evidence includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) mimicry by exogenously applied ATP of the action of nerve-released transmitter; (4) the presence of Mg2+-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) the similar blocking and potentiating effects produced by drugs on the responses to exogenously applied ATP and nerve stimulation. A tentative model for the synthesis, storage, release and inactivation of ATP during purinergic nerve transmission is proposed. Some properties of purinergic receptors are described.", "contents": "The purinergic nerve hypothesis. Experiments over the past decade have revealed a third component in the autonomic nervous system which is neither adrenergic nor cholinergic. These nerves are strongly represented in the gastrointestinal tract of a wide range of vertebrate species and have also been identified in lung, trachea, retractor penis, bladder, oesophagus, eye, seminal vesicle and in some parts of the cardiovascular system and brain. Evidence has been presented that the principal active substance released by these nerves in the gut is a purine nucleotide, probably ATP, and they have therefore been termed 'purinergic'. The evidence includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) mimicry by exogenously applied ATP of the action of nerve-released transmitter; (4) the presence of Mg2+-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) the similar blocking and potentiating effects produced by drugs on the responses to exogenously applied ATP and nerve stimulation. A tentative model for the synthesis, storage, release and inactivation of ATP during purinergic nerve transmission is proposed. Some properties of purinergic receptors are described."}
{"id": "PMID:24535", "title": "Functional maturation of the epididymis in rabbit and rhesus monkey.", "content": "The changes in the weight, histology and biochemical composition of the epididymis (caput, corpus and cauda segments) in prepuberal rabbit and rhesus monkey in response to testosterone treatment were investigated. The increase in the weight of the organ was accompanied by increased levels of RNA and DNA. Androgen therapy caused an increase in the concentration of sialic acid, phospholipids and glycerylphosphorylcholine and activities of alkaline phosphatase, acid phosphatase and hyaluronidase. The cauda region of the epididymis exhibited relatively higher levels of sialic acid and glycerylphosphorylcholine. These findings are discussed in relation to the functional maturation of the organ and the role of androgen in this process.", "contents": "Functional maturation of the epididymis in rabbit and rhesus monkey. The changes in the weight, histology and biochemical composition of the epididymis (caput, corpus and cauda segments) in prepuberal rabbit and rhesus monkey in response to testosterone treatment were investigated. The increase in the weight of the organ was accompanied by increased levels of RNA and DNA. Androgen therapy caused an increase in the concentration of sialic acid, phospholipids and glycerylphosphorylcholine and activities of alkaline phosphatase, acid phosphatase and hyaluronidase. The cauda region of the epididymis exhibited relatively higher levels of sialic acid and glycerylphosphorylcholine. These findings are discussed in relation to the functional maturation of the organ and the role of androgen in this process."}
{"id": "PMID:24536", "title": "Further evidence of teratogenic effects apparently produced by neurotransmitters during brain differentiation.", "content": "1. Adult male rats treated neonatally with the monoamine oxidase inhibitor pargyline showed significantly increased nuclear volumes of the nerve cells in the medial and central amygdaloid nuclei and significantly decreased concentrations of noradrenaline and dopamine in the hypothalamus as compared to control males. 2. Adult male rats treated neonatally with the monoamine depletor reserpine also displayed increased nuclear volumes of the nerve cells in the medial and central amygdaloid nuclei in comparison to the control males but significantly decreased nuclear volumes in comparison to the pargylinized males. Furthermore, the number of synapses in the stratum radiatum (CA 1-region) of the hippocampus was significantly decreased in the reserpinized males in comparison to the control males. 3. Adult male rats treated neonatally with the acetylcholine esterase inhibitor pyridostigmine showed a slight decrease of the noradrenaline concentration in the hypothalamus. These findings suggest that changes of neurotransmitter concentrations and/or turnover rates apparently produced by psychotrophic drugs during brain differentiation are able to exert teratogenic effects.", "contents": "Further evidence of teratogenic effects apparently produced by neurotransmitters during brain differentiation. 1. Adult male rats treated neonatally with the monoamine oxidase inhibitor pargyline showed significantly increased nuclear volumes of the nerve cells in the medial and central amygdaloid nuclei and significantly decreased concentrations of noradrenaline and dopamine in the hypothalamus as compared to control males. 2. Adult male rats treated neonatally with the monoamine depletor reserpine also displayed increased nuclear volumes of the nerve cells in the medial and central amygdaloid nuclei in comparison to the control males but significantly decreased nuclear volumes in comparison to the pargylinized males. Furthermore, the number of synapses in the stratum radiatum (CA 1-region) of the hippocampus was significantly decreased in the reserpinized males in comparison to the control males. 3. Adult male rats treated neonatally with the acetylcholine esterase inhibitor pyridostigmine showed a slight decrease of the noradrenaline concentration in the hypothalamus. These findings suggest that changes of neurotransmitter concentrations and/or turnover rates apparently produced by psychotrophic drugs during brain differentiation are able to exert teratogenic effects."}
{"id": "PMID:24537", "title": "Different effects of amygdaloid lesions on compensatory ovarian hypertrophy in cyclic and prepubertal female rats.", "content": "Cyclic and 28-day-old immature female rats were hemiovariectomized and partly bilaterally lesioned in the cortical amygdaloid nucleus (CAN). The compensatory ovarian hypertrophy (COH) recorded in the adult females on the 8th day after hemicastration was completely prevented by the amygdaloid lesions. In contrast, damage to the CAN did not alter the ovarian weight in prepubertal females, although COH was also induced in these animals by unilateral ovariectomy.", "contents": "Different effects of amygdaloid lesions on compensatory ovarian hypertrophy in cyclic and prepubertal female rats. Cyclic and 28-day-old immature female rats were hemiovariectomized and partly bilaterally lesioned in the cortical amygdaloid nucleus (CAN). The compensatory ovarian hypertrophy (COH) recorded in the adult females on the 8th day after hemicastration was completely prevented by the amygdaloid lesions. In contrast, damage to the CAN did not alter the ovarian weight in prepubertal females, although COH was also induced in these animals by unilateral ovariectomy."}
{"id": "PMID:24538", "title": "Investigation of the mechanism of the methylmalonyl-CoA mutase reaction with the substrate analogue: ethylmalonyl-CoA.", "content": "1. Ethylmalonyl-CoA was found to be a substrate for methylmalonyl-CoA mutase from Propionibacterium shermanii, the product being mainly (2R)-methylsuccinyl-CoA along with some (2S)-diastereoisomer. 2. The relevant 1H-nuclear magnetic resonance signals of methylsuccinic acid and of its dimethyl ester were assigned to the diastereotopic methylene hydrogens using sterospecifically dideuterated specimens of known configuration. 3. [2(-2)H1]Ethylmalonyl-CoA was converted by methylmalonyl-CoA mutase in 2H2O mainly to (2R, 3S)-[3(-2)H1]methylsuccinyl-CoA. No dideuterated product was observed. 4. Starting from (1R)-[1(-2)H1]-ethathanol, (1S)-[1(-2)H1]ethanol and [2H6] ethanol the following deuterated specimens of ethylmalonic acid were synthesised and characterised: (3S)-[3(-2)H1], (3R)-[3(-2)H1] and [3(-2)H2, 4(-2)H3], respectively. 5. Conversion of (3S)-[3(-2)H1]-ethylmalonyl-CoA (70% 2H1 and 2% 2H2 species) on the mutase in water afforded mainly (2R)-[2(-2)H1]methylsuccinyl-CoA along with some (2S)-diastereoisomer. No deuterium loss was observed. 6. Methylmalonyl-CoA mutase converted (3R)-[3(-2)H1]ethylmalonyl-CoA (81% 2H1 and 2% 2H2 species) to the following methylsuccinyl-CoA species: 33% [3(-2)H1], the deuterium being in the threo position with respect to the methyl group; 21% [2(-2)H1]; 46% unlabelled. The ratio of the species with (2R) and (2S) configuration was about 60:40. 7. Reaction of [3(-2)H2, 4(-2)H3]ethylmalonyl-CoA (94.5% [2H5] species) with the mutase gave the following labelled methylsuccinyl-CoA species:53.4% [methyl-2H3, 2(-2)H1, 3(-2)H1], the 3-deuterium being in the threo position with respect to the methyl group; 37.6% [methyl-2H3, 2(-2)H1]; 5% [methyl(-2)H3, 2(-2)H1, 2(-2)H1, 3(-2)H1] the 3-deuterium being in erythro position with respect to the methyl group; 4% [methyl(-2)H3, 3(-2)H1]. The ratio of the species with (2R) and (2S) configuration was about 70:30. 8. Implications of these findings for the mechanism of the rearrangements catalysed by coenzyme B12 are discussed.", "contents": "Investigation of the mechanism of the methylmalonyl-CoA mutase reaction with the substrate analogue: ethylmalonyl-CoA. 1. Ethylmalonyl-CoA was found to be a substrate for methylmalonyl-CoA mutase from Propionibacterium shermanii, the product being mainly (2R)-methylsuccinyl-CoA along with some (2S)-diastereoisomer. 2. The relevant 1H-nuclear magnetic resonance signals of methylsuccinic acid and of its dimethyl ester were assigned to the diastereotopic methylene hydrogens using sterospecifically dideuterated specimens of known configuration. 3. [2(-2)H1]Ethylmalonyl-CoA was converted by methylmalonyl-CoA mutase in 2H2O mainly to (2R, 3S)-[3(-2)H1]methylsuccinyl-CoA. No dideuterated product was observed. 4. Starting from (1R)-[1(-2)H1]-ethathanol, (1S)-[1(-2)H1]ethanol and [2H6] ethanol the following deuterated specimens of ethylmalonic acid were synthesised and characterised: (3S)-[3(-2)H1], (3R)-[3(-2)H1] and [3(-2)H2, 4(-2)H3], respectively. 5. Conversion of (3S)-[3(-2)H1]-ethylmalonyl-CoA (70% 2H1 and 2% 2H2 species) on the mutase in water afforded mainly (2R)-[2(-2)H1]methylsuccinyl-CoA along with some (2S)-diastereoisomer. No deuterium loss was observed. 6. Methylmalonyl-CoA mutase converted (3R)-[3(-2)H1]ethylmalonyl-CoA (81% 2H1 and 2% 2H2 species) to the following methylsuccinyl-CoA species: 33% [3(-2)H1], the deuterium being in the threo position with respect to the methyl group; 21% [2(-2)H1]; 46% unlabelled. The ratio of the species with (2R) and (2S) configuration was about 60:40. 7. Reaction of [3(-2)H2, 4(-2)H3]ethylmalonyl-CoA (94.5% [2H5] species) with the mutase gave the following labelled methylsuccinyl-CoA species:53.4% [methyl-2H3, 2(-2)H1, 3(-2)H1], the 3-deuterium being in the threo position with respect to the methyl group; 37.6% [methyl-2H3, 2(-2)H1]; 5% [methyl(-2)H3, 2(-2)H1, 2(-2)H1, 3(-2)H1] the 3-deuterium being in erythro position with respect to the methyl group; 4% [methyl(-2)H3, 3(-2)H1]. The ratio of the species with (2R) and (2S) configuration was about 70:30. 8. Implications of these findings for the mechanism of the rearrangements catalysed by coenzyme B12 are discussed."}
{"id": "PMID:24539", "title": "The value of bilateral biopsy in unilateral cryptorchidism.", "content": "Here are the results of bilateral biopsies on 52 cases of unilateral cryptorchidia. In 12 patients the scrotal testicle showed equal lesions or more important lesions in the undescended testicle. It points out the importance of systematizing the histological testicular study, keeping in mind: (1) spermatogenic index; (2) variation in spermatogonias; (3) tubular diameter, and (4) interstitial tissue. Stress is made on the innocuousness of the bilateral testicular biopsy and its indispensability since it is the only way to recognize a dysgenetic cryptorchidia and evaluate the future fertility of the patient.", "contents": "The value of bilateral biopsy in unilateral cryptorchidism. Here are the results of bilateral biopsies on 52 cases of unilateral cryptorchidia. In 12 patients the scrotal testicle showed equal lesions or more important lesions in the undescended testicle. It points out the importance of systematizing the histological testicular study, keeping in mind: (1) spermatogenic index; (2) variation in spermatogonias; (3) tubular diameter, and (4) interstitial tissue. Stress is made on the innocuousness of the bilateral testicular biopsy and its indispensability since it is the only way to recognize a dysgenetic cryptorchidia and evaluate the future fertility of the patient."}
{"id": "PMID:24540", "title": "Studies on beta-adrenoceptors mediating changes in mechanical events and adenosine 3',5'-monophosphate levels. Rat atria.", "content": "Increasing concentrations of the functional antagonist carbachol resulted in a shift to the right of the dose-response curves for (--)-isoproterenol-induced positive chronotropic and inotropic responses and a reduction of the maximum degree of response that could be produced relative to that produced by theophylline. Carbachol only reduced the maximum responses to the partial agonist (--)-soterenol. The ED50 value for isoproterenol-induced increases in adenosine 3',5'-monophosphate (cyclic AMP) levels was more than 10-fold larger than those for production of mechanical events and soterenol did not produce a measurable increase in cyclic AMP above baseline values. Soterenol was analyzed as a competitive antagonist of isoproterenol-induced responses and the apparent dissociation constants (KA) for soterenol calculated to be 1.21 X 10(-7) M for receptors mediating positive chronotropic responses, 3.56 X 10(-7) M for receptors mediating positive inotropic responses, and 2.96 X 10(-7) M for receptors mediating increases in cyclic AMP levels. By two additional theoretical models of drug-receptor interactions, the KA values for soterenol were between 1.5 and 4.5 X 10(-7) M. These KA values were essentially the same as the ED50 values for soterenol-induced mechanical effects. By one of the models, the KA for isoproterenol was calculated to be about 2.14 X 10(-8) M, a value close to the ED50 value for isoproterenol-induced increases in cyclic AMP (5.45 X 10(-8) M). These results suggest that the beta-adrenoceptors mediating the three responses in rat atria are of the same type and that differences in concentrations required to produce mechanical vs. cyclic AMP changes results with agonists possessing high efficacy for which there is a receptor reserve.", "contents": "Studies on beta-adrenoceptors mediating changes in mechanical events and adenosine 3',5'-monophosphate levels. Rat atria. Increasing concentrations of the functional antagonist carbachol resulted in a shift to the right of the dose-response curves for (--)-isoproterenol-induced positive chronotropic and inotropic responses and a reduction of the maximum degree of response that could be produced relative to that produced by theophylline. Carbachol only reduced the maximum responses to the partial agonist (--)-soterenol. The ED50 value for isoproterenol-induced increases in adenosine 3',5'-monophosphate (cyclic AMP) levels was more than 10-fold larger than those for production of mechanical events and soterenol did not produce a measurable increase in cyclic AMP above baseline values. Soterenol was analyzed as a competitive antagonist of isoproterenol-induced responses and the apparent dissociation constants (KA) for soterenol calculated to be 1.21 X 10(-7) M for receptors mediating positive chronotropic responses, 3.56 X 10(-7) M for receptors mediating positive inotropic responses, and 2.96 X 10(-7) M for receptors mediating increases in cyclic AMP levels. By two additional theoretical models of drug-receptor interactions, the KA values for soterenol were between 1.5 and 4.5 X 10(-7) M. These KA values were essentially the same as the ED50 values for soterenol-induced mechanical effects. By one of the models, the KA for isoproterenol was calculated to be about 2.14 X 10(-8) M, a value close to the ED50 value for isoproterenol-induced increases in cyclic AMP (5.45 X 10(-8) M). These results suggest that the beta-adrenoceptors mediating the three responses in rat atria are of the same type and that differences in concentrations required to produce mechanical vs. cyclic AMP changes results with agonists possessing high efficacy for which there is a receptor reserve."}
{"id": "PMID:24541", "title": "Cardiovascular responses to intraventricular adrenaline in spontaneous hypertensive rats.", "content": "The effects of intracerebroventricular (i.c.v.) injections of adrenaline on the blood pressure and heart rate of spontaneous hypertensive (SH) rats have been investigated. Adrenaline induced dose-related falls in blood pressure and heart rate in both conscious and urethane anaesthetised rats. In conscious rats, the hypotension and metoprolol, but were unaffected by pretreatment with phentolamine, piperoxan, fluphenazine or methysergide. However, in urethane-anaesthetised rats, the hypotension and bradycardia induced by i.c.v. adrenaline was not significantly affected by i.c.v. pretreatment with propranolol or oxprenolol, while metoprolol significantly antagonised only the bradycardia. Piperoxan, fluphenazine and methysergide were also without effect. Pretreatment with mecamylamine (i.p.) abolished the cardiovascular depressor effects of i.c.v. adrenaline in both conscious and urethane anaesthetised SH rats. It is concluded that the cardiovascular depressor effects of i.c.v. adrenaline are mediated by central adrenoceptors in SH rats and that, in conscious rats, these depressor effects may be mediated by central beta-adrenoceptors rather than alpha-adrenoceptors.", "contents": "Cardiovascular responses to intraventricular adrenaline in spontaneous hypertensive rats. The effects of intracerebroventricular (i.c.v.) injections of adrenaline on the blood pressure and heart rate of spontaneous hypertensive (SH) rats have been investigated. Adrenaline induced dose-related falls in blood pressure and heart rate in both conscious and urethane anaesthetised rats. In conscious rats, the hypotension and metoprolol, but were unaffected by pretreatment with phentolamine, piperoxan, fluphenazine or methysergide. However, in urethane-anaesthetised rats, the hypotension and bradycardia induced by i.c.v. adrenaline was not significantly affected by i.c.v. pretreatment with propranolol or oxprenolol, while metoprolol significantly antagonised only the bradycardia. Piperoxan, fluphenazine and methysergide were also without effect. Pretreatment with mecamylamine (i.p.) abolished the cardiovascular depressor effects of i.c.v. adrenaline in both conscious and urethane anaesthetised SH rats. It is concluded that the cardiovascular depressor effects of i.c.v. adrenaline are mediated by central adrenoceptors in SH rats and that, in conscious rats, these depressor effects may be mediated by central beta-adrenoceptors rather than alpha-adrenoceptors."}
{"id": "PMID:24542", "title": "Beta-adrenoceptors modulate noradrenaline release from axonal sprouts in cultured rat superior cervical ganglia.", "content": "Superior cervical ganglia of rats grown in organ culture were used to study the effect of beta-receptor stimulants and antagonists on 3H-noradrenaline release in response to stimulation by KC1 (75 mM). (--)-Isoprenaline 1X 10(-9)--1 X 10(-7) M) increased 20--25% the release of 3H-noradrenaline from cultured ganglia exposed to KC1. Isoprenaline did not modify either the spontaneous (non-calcium dependent) release of 3H-noradrenaline from cultured ganglia, or the KC1-stimulated release from fresh ganglia. The effect of (--)-isoprenaline was blocked by (--)-propranolol 5 X 10(-9) -- 1 X 10(-8) M and by butoxamine 10(-6) M, but not by (+)-propranolol (1 -- 5 X 10(-8) M), practolol (1 X 10(-8) -- 1 X 10(-6) M), or sotalol (1 X 10(-7) -- 1 X 10(-6) M). Isoprenaline induced augmentation of 3H-noradrenaline release and its antagonism by (--)-propranolol still occurred in the presence of DMI. It is suggested that presynaptic beta-receptors in sympathetic nerve terminals may be involved in a positive feedback of noradrenaline release.", "contents": "Beta-adrenoceptors modulate noradrenaline release from axonal sprouts in cultured rat superior cervical ganglia. Superior cervical ganglia of rats grown in organ culture were used to study the effect of beta-receptor stimulants and antagonists on 3H-noradrenaline release in response to stimulation by KC1 (75 mM). (--)-Isoprenaline 1X 10(-9)--1 X 10(-7) M) increased 20--25% the release of 3H-noradrenaline from cultured ganglia exposed to KC1. Isoprenaline did not modify either the spontaneous (non-calcium dependent) release of 3H-noradrenaline from cultured ganglia, or the KC1-stimulated release from fresh ganglia. The effect of (--)-isoprenaline was blocked by (--)-propranolol 5 X 10(-9) -- 1 X 10(-8) M and by butoxamine 10(-6) M, but not by (+)-propranolol (1 -- 5 X 10(-8) M), practolol (1 X 10(-8) -- 1 X 10(-6) M), or sotalol (1 X 10(-7) -- 1 X 10(-6) M). Isoprenaline induced augmentation of 3H-noradrenaline release and its antagonism by (--)-propranolol still occurred in the presence of DMI. It is suggested that presynaptic beta-receptors in sympathetic nerve terminals may be involved in a positive feedback of noradrenaline release."}
{"id": "PMID:24543", "title": "Evidence that the efficacy (intrinsic activity) of fenoterol is higher than that of salbutamol on beta-adrenoceptors in guinea-pig trachea.", "content": "The functional antagonism of carbachol by fenoterol and salbutamol (beta-adrenoceptor agonists) has been used to demonstrate that the efficacy (intrinsic activity) of fenoterol was about twice that of salbutamol on guinea-pig trachea. The mean maximum shifts of the carbachol concentration--response lines by fenoterol and salbutamol were (log units) 1.07 +/- 0.07 (n = 5) and 0.64 +/- 0.07 (n = 5) respectively. This difference in their efficacies could be demonstrated as differences in maximum relaxation on tracheal preparations contracted with carbachol, although this was dependent on the concentration of carbachol used. beta-Adrenoceptor blocking properties of salbutamol (1 mM) but not fenoterol (1 mM) could be demonstrated on trachea in that salbutamol, but not fenoterol, antagonised the shift in the carbachol concentration--response line produced by isoprenaline. The implications of these findings in relation to the use of fenoterol and salbutamol as bronchodilators is discussed.", "contents": "Evidence that the efficacy (intrinsic activity) of fenoterol is higher than that of salbutamol on beta-adrenoceptors in guinea-pig trachea. The functional antagonism of carbachol by fenoterol and salbutamol (beta-adrenoceptor agonists) has been used to demonstrate that the efficacy (intrinsic activity) of fenoterol was about twice that of salbutamol on guinea-pig trachea. The mean maximum shifts of the carbachol concentration--response lines by fenoterol and salbutamol were (log units) 1.07 +/- 0.07 (n = 5) and 0.64 +/- 0.07 (n = 5) respectively. This difference in their efficacies could be demonstrated as differences in maximum relaxation on tracheal preparations contracted with carbachol, although this was dependent on the concentration of carbachol used. beta-Adrenoceptor blocking properties of salbutamol (1 mM) but not fenoterol (1 mM) could be demonstrated on trachea in that salbutamol, but not fenoterol, antagonised the shift in the carbachol concentration--response line produced by isoprenaline. The implications of these findings in relation to the use of fenoterol and salbutamol as bronchodilators is discussed."}
{"id": "PMID:24544", "title": "Antagonism by mianserin and classical alpha-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine.", "content": "Antagonism of pressor responses to sympathetic outflow stimulation and alpha-adrenoceptor agonists in pithed spontaneously hypertensive rats was used to estimate postsynaptic alpha-adrenoceptor blocking activity of mianserin, phentolamine, phenoxybenzamine, piperoxan and yohimbine. Estimation of presynaptic alpha-adrenoceptor blocking activity of these drugs was obtained by studying their ability to antagonize clonidine-induced suppression of positive chronotropic responses to sympathetic outflow stimulation. In this manner, evidence was obtained that mianserin causes selective presynaptic alpha-adrenoceptor blockade. Mianserin, piperoxan and yohimbine antagonized clonidine-induced avoidance blockade or hypotension in spontaneously hypertensive rats, but methysergide, phenoxybenzamine and phentolamine were ineffective. These results suggest that mianserin may antagonize the central effects of clonidine by blockade of noradrenergic presynaptic or autoreceptors and possibly explain the antidepressant effect of mianserin as due to indirect activation of central noradrenergic neurons.", "contents": "Antagonism by mianserin and classical alpha-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine. Antagonism of pressor responses to sympathetic outflow stimulation and alpha-adrenoceptor agonists in pithed spontaneously hypertensive rats was used to estimate postsynaptic alpha-adrenoceptor blocking activity of mianserin, phentolamine, phenoxybenzamine, piperoxan and yohimbine. Estimation of presynaptic alpha-adrenoceptor blocking activity of these drugs was obtained by studying their ability to antagonize clonidine-induced suppression of positive chronotropic responses to sympathetic outflow stimulation. In this manner, evidence was obtained that mianserin causes selective presynaptic alpha-adrenoceptor blockade. Mianserin, piperoxan and yohimbine antagonized clonidine-induced avoidance blockade or hypotension in spontaneously hypertensive rats, but methysergide, phenoxybenzamine and phentolamine were ineffective. These results suggest that mianserin may antagonize the central effects of clonidine by blockade of noradrenergic presynaptic or autoreceptors and possibly explain the antidepressant effect of mianserin as due to indirect activation of central noradrenergic neurons."}
{"id": "PMID:24562", "title": "[A double adsorption technique for the determination of corticosteroid-binding globulin in human serum (author's transl)].", "content": "Despite the widespread use of many different estrogenic compounds in hormonal contraception and estrogen replacement, in the human a simple test for comparing the potencies of the compounds is lacking. Many of the estrogenic compounds are difficult to measure, and animal studies may not relate directly to those done on humans in terms of potency. Corticosteroid-binding globulin (CBG) in human serum has been known since 1958 to increase in response to estrogen administration, and the degree of its elevation has been shown to be closely dose-related and reasonably sensitive. Therefore, CBG represents a biological parameter that provides for the specific quantal analysis of estrogenicity in the human. In this paper a simple and reliable method for the determination of the cortisol-binding capacity of CBG (CBG-BC) in human serum is described. The procedure is based on the amount of cortisol required to saturate the CBG binding sites. All endogenous steroids are initially removed from the serum by adsorption on dextran-coated charcoal (DCC). A mixture of a known amount of unlabeled and labeled cortisol is added to the sample in order to saturate the \"stripped\" binding sites of CBG. The unbound cortisol is removed by DCC at 4 degrees C, and the supernatant represents the total cortisol-binding capacity of the serum sample. To distinguish between cortisol-binding to CBG and to albumin, \"stripped\" serum is heated for 30 min at 60 degrees C, the temperature which does not influence cortisol binding by albumin but which does inactivate CBG. The samples are subsequently equilibrated with a mixture of labeled and unlabeled cortisol. The free cortisol is removed by DCC and the bound cortisol remaining in the supernatant is designated as the albumin-bound cortisol. Thus, CBG-BC is assayed by a double adsorption technique as differential binding to native and heat-inactivated serum. The cortisol determined by this method corresponds to CBG-bound cortisol, and CBG-BC is expressed as micrograms of cortisol bound per 100 ml serum. The precision and accuracy of the method were found to be good. The values of CBG-BC obtained by this method were 14.9 +/- 1.9 (SD) microgram/100ml in adult men and 16.0 +/- 1.8 microgram/100ml in adult women. Daily serum samples in five women revealed no significant variations in CBG-BC throughout the normal menstrual cycle despite fluctuating levels of serum estradiol. CBG-BC was also found not to vary significantly with age. In pregnancy, however CBG-BC increased significantly.", "contents": "[A double adsorption technique for the determination of corticosteroid-binding globulin in human serum (author's transl)]. Despite the widespread use of many different estrogenic compounds in hormonal contraception and estrogen replacement, in the human a simple test for comparing the potencies of the compounds is lacking. Many of the estrogenic compounds are difficult to measure, and animal studies may not relate directly to those done on humans in terms of potency. Corticosteroid-binding globulin (CBG) in human serum has been known since 1958 to increase in response to estrogen administration, and the degree of its elevation has been shown to be closely dose-related and reasonably sensitive. Therefore, CBG represents a biological parameter that provides for the specific quantal analysis of estrogenicity in the human. In this paper a simple and reliable method for the determination of the cortisol-binding capacity of CBG (CBG-BC) in human serum is described. The procedure is based on the amount of cortisol required to saturate the CBG binding sites. All endogenous steroids are initially removed from the serum by adsorption on dextran-coated charcoal (DCC). A mixture of a known amount of unlabeled and labeled cortisol is added to the sample in order to saturate the \"stripped\" binding sites of CBG. The unbound cortisol is removed by DCC at 4 degrees C, and the supernatant represents the total cortisol-binding capacity of the serum sample. To distinguish between cortisol-binding to CBG and to albumin, \"stripped\" serum is heated for 30 min at 60 degrees C, the temperature which does not influence cortisol binding by albumin but which does inactivate CBG. The samples are subsequently equilibrated with a mixture of labeled and unlabeled cortisol. The free cortisol is removed by DCC and the bound cortisol remaining in the supernatant is designated as the albumin-bound cortisol. Thus, CBG-BC is assayed by a double adsorption technique as differential binding to native and heat-inactivated serum. The cortisol determined by this method corresponds to CBG-bound cortisol, and CBG-BC is expressed as micrograms of cortisol bound per 100 ml serum. The precision and accuracy of the method were found to be good. The values of CBG-BC obtained by this method were 14.9 +/- 1.9 (SD) microgram/100ml in adult men and 16.0 +/- 1.8 microgram/100ml in adult women. Daily serum samples in five women revealed no significant variations in CBG-BC throughout the normal menstrual cycle despite fluctuating levels of serum estradiol. CBG-BC was also found not to vary significantly with age. In pregnancy, however CBG-BC increased significantly."}
{"id": "PMID:24563", "title": "The protective effect of ketotifen in bronchial asthma.", "content": "Thirty-six patients with confirmed allergic bronchial asthma were divided into 3 parallel groups and treated with ketotifen 1 mg b.i.d. (Group I), ketotifen 2 mg b.i.d. (Group II), and clemastine 1 mg b.i.d. (Group III) respectively for 6 months. Nine out of 12 patients in Group I and 10 out of 12 in Group II experienced a statistically significant improvement in dyspnoea and in pulmonary function (Tiffeneau test). Likewise there was a marked reduction in the number, severity and average duration (minutes per week) of asthmatic attacks. By the 12th week, 8 out of 12 patients in the clemastine group had dropped out because of inefficacy. Ketotifen was very well tolerated by all the patients. In both ketotifen groups pathological eosinophil counts returned to normal during treatment. It can be concluded that ketotifen is effective in the long-term prophylaxis of bronchial asthma.", "contents": "The protective effect of ketotifen in bronchial asthma. Thirty-six patients with confirmed allergic bronchial asthma were divided into 3 parallel groups and treated with ketotifen 1 mg b.i.d. (Group I), ketotifen 2 mg b.i.d. (Group II), and clemastine 1 mg b.i.d. (Group III) respectively for 6 months. Nine out of 12 patients in Group I and 10 out of 12 in Group II experienced a statistically significant improvement in dyspnoea and in pulmonary function (Tiffeneau test). Likewise there was a marked reduction in the number, severity and average duration (minutes per week) of asthmatic attacks. By the 12th week, 8 out of 12 patients in the clemastine group had dropped out because of inefficacy. Ketotifen was very well tolerated by all the patients. In both ketotifen groups pathological eosinophil counts returned to normal during treatment. It can be concluded that ketotifen is effective in the long-term prophylaxis of bronchial asthma."}
{"id": "PMID:24570", "title": "Effect of lactulose on ammonia production in a fecal incubation system.", "content": "An in vitro fecal incubation system was used to demonstrate how lactulose influences ammonia metabolism in the colon. Lactulose and other fermentable substrates (glucose, mannitol, and sorbitol), pH and organic acid were varied independently so that their different effects could be determined. Fermentable substrate caused a fall in ammonia concentration during the period of fermentation. Acidification to pH 5.0 or less, with hydrochloric acid or a lactic-acetic acid mixture, significantly reduced ammonia generation, but unlike fermentable substrates, did not lower the existing ammonia concentration. The lactic-acetic acid mixture did not reduce ammonia generation significantly below that found with acidification by hydrochloric acid. The effect of lactulose in reducing ammonia concentration is attributed to its role as a bacterial substrate in either increasing bacterial assimilation of ammonia or reducing deamination of nitrogenous compounds. The effect of low pH in reducing generation of ammonia appears to be part of a general reduction in bacterial metabolism.", "contents": "Effect of lactulose on ammonia production in a fecal incubation system. An in vitro fecal incubation system was used to demonstrate how lactulose influences ammonia metabolism in the colon. Lactulose and other fermentable substrates (glucose, mannitol, and sorbitol), pH and organic acid were varied independently so that their different effects could be determined. Fermentable substrate caused a fall in ammonia concentration during the period of fermentation. Acidification to pH 5.0 or less, with hydrochloric acid or a lactic-acetic acid mixture, significantly reduced ammonia generation, but unlike fermentable substrates, did not lower the existing ammonia concentration. The lactic-acetic acid mixture did not reduce ammonia generation significantly below that found with acidification by hydrochloric acid. The effect of lactulose in reducing ammonia concentration is attributed to its role as a bacterial substrate in either increasing bacterial assimilation of ammonia or reducing deamination of nitrogenous compounds. The effect of low pH in reducing generation of ammonia appears to be part of a general reduction in bacterial metabolism."}
{"id": "PMID:24576", "title": "How thyroid disease presents in the elderly.", "content": "Some of the symptoms and signs of hypothyroidism and hyperthyroidism in elderly patients may be mistakenly attributed to \"old age.\" Weight loss, muscle weakness, tremor, angina, congestive heart failure--all signs of hyperthyroidism--are also concomitants of aging. Fatigue, sluggishness, withdrawal behavior, senile atrophic skin changes--all signs of hypothroidism--are also a part of the normal aging process. Although screening elderly people for thyroid disease is economically unsound, the physician should maintain a high index of suspicion of its presence. Laboratory tests must be interpreted with extra care. Values of 131I uptake, serum T4 and T3, thyroid-stimulating hormone, and thyrotropin-releasing hormone are all helpful in diagnosis. Thyroid disease is easily treated in elderly patients, and results often are dramatic. Propranolol is effective in thyrotoxic patients when symptoms require prompt relief. The definitive treatment, however, is 131I; antithyroid drugs are difficult to manage. Hypothyroidism is easily treated with T4.", "contents": "How thyroid disease presents in the elderly. Some of the symptoms and signs of hypothyroidism and hyperthyroidism in elderly patients may be mistakenly attributed to \"old age.\" Weight loss, muscle weakness, tremor, angina, congestive heart failure--all signs of hyperthyroidism--are also concomitants of aging. Fatigue, sluggishness, withdrawal behavior, senile atrophic skin changes--all signs of hypothroidism--are also a part of the normal aging process. Although screening elderly people for thyroid disease is economically unsound, the physician should maintain a high index of suspicion of its presence. Laboratory tests must be interpreted with extra care. Values of 131I uptake, serum T4 and T3, thyroid-stimulating hormone, and thyrotropin-releasing hormone are all helpful in diagnosis. Thyroid disease is easily treated in elderly patients, and results often are dramatic. Propranolol is effective in thyrotoxic patients when symptoms require prompt relief. The definitive treatment, however, is 131I; antithyroid drugs are difficult to manage. Hypothyroidism is easily treated with T4."}
{"id": "PMID:24578", "title": "[Cardiomyopathies].", "content": "A) Definition and classification. Cardiomyopathy is defined as a dysfunction of cardiac muscle of unknown origin and classified according to genetic, morphological and functional criteria as follows: 1. cardiomyopathy of autosomal dominant inheritance with asymmetric septal hypertrophy (ASH) a) obstructive b) non obstructive 2. cardiomyopathy of autosomal dominant inheritance without ASH 3. cardiomyopathy of autosomal recessive inheritance 4. sporadic cardiomyopathy. It is assumed that at least the cardiomyopathies listed here are heterogeneous groups that have to be subdivided as soon as further discriminating findings--structural or enzymatic--are available. B) Diagnosis, prognosis, treatment. The diagnostic methods are evaluated, the prognosis and the treatment of the cardiomyopathies are reviewed.", "contents": "[Cardiomyopathies]. A) Definition and classification. Cardiomyopathy is defined as a dysfunction of cardiac muscle of unknown origin and classified according to genetic, morphological and functional criteria as follows: 1. cardiomyopathy of autosomal dominant inheritance with asymmetric septal hypertrophy (ASH) a) obstructive b) non obstructive 2. cardiomyopathy of autosomal dominant inheritance without ASH 3. cardiomyopathy of autosomal recessive inheritance 4. sporadic cardiomyopathy. It is assumed that at least the cardiomyopathies listed here are heterogeneous groups that have to be subdivided as soon as further discriminating findings--structural or enzymatic--are available. B) Diagnosis, prognosis, treatment. The diagnostic methods are evaluated, the prognosis and the treatment of the cardiomyopathies are reviewed."}
{"id": "PMID:24577", "title": "Forensic considerations on the comparison of \"serum gamma-glutamyltranspeptidase\" (\"gamma-GT) activity in experimental acute alcoholic intoxication and in alcoholic car drivers who caused road accidents.", "content": "The authors studied blood alcohol levels and serum gamma-GT activity in 18 drivers who caused car accidents while intoxicated, and in 20 young volunteer subjects without any hepatic damage, in which an acute alcoholic intoxication was present. In most of the drivers the serum gamma-GT activity was significantly higher than in the volunteers, which strongly suggests a chronic alcoholic intoxication. In the 20 volunteers, who were occasional drinkers, the serum gamma-GT activity did not show pathological values even in a state of heavy intoxication. According to the authors, the serum gamma-GT determination could be made obligatory by law, in order to differentiate between acute or chronic alcoholic intoxication. Should an intoxicated driver be found guilty of an offense, this fact could aggravate the circumstances. Furthermore serum gamma-GT activity determination could be used as an evaluating parameter in granting driving licences.", "contents": "Forensic considerations on the comparison of \"serum gamma-glutamyltranspeptidase\" (\"gamma-GT) activity in experimental acute alcoholic intoxication and in alcoholic car drivers who caused road accidents. The authors studied blood alcohol levels and serum gamma-GT activity in 18 drivers who caused car accidents while intoxicated, and in 20 young volunteer subjects without any hepatic damage, in which an acute alcoholic intoxication was present. In most of the drivers the serum gamma-GT activity was significantly higher than in the volunteers, which strongly suggests a chronic alcoholic intoxication. In the 20 volunteers, who were occasional drinkers, the serum gamma-GT activity did not show pathological values even in a state of heavy intoxication. According to the authors, the serum gamma-GT determination could be made obligatory by law, in order to differentiate between acute or chronic alcoholic intoxication. Should an intoxicated driver be found guilty of an offense, this fact could aggravate the circumstances. Furthermore serum gamma-GT activity determination could be used as an evaluating parameter in granting driving licences."}
{"id": "PMID:24583", "title": "Modification of the immunologic properties of the cell surface.", "content": "Living CF1 mouse-transplantable spontaneous mammary adenocarcinoma cells were modified with glutaraldehyde, formalin, 2,4,6-trinitrophenylate, Vibrio cholerae neurominidase, iodoacetate, heparin, histamine and adenosine 3'5'-monophosphate (cAMP), then used to immunize syngeneic CF1 mice. Animals immunized with the fixed (formalinized or glutaraldehyde fixed) neuraminidase-treated cells or the membrane of these cells, rejected two challenging doses of 10(8) viable unmodified adenocarcinoma cells. Animals immunized with adenocarcinoma cells treated with neuraminidase (170 IU/5x10(5) cells) or with the spontaneous adenocarcinoma-cell surface glycoprotein, rejected the first challenging dose but developed tumors and died on the second challenge with the viable untreated adenocarcinoma cells. Animals immunized with the adenocarcinoma cells pretreated with trinitrophenylate, glutaraldehyde or formalin, developed temporary resistance to the spontaneous mammary adenocarcinoma. Adenocarcinoma cells pretreated with NaF, iodoacetate, heparin, EDTA, Colchicine or histamine showed reduced oncogenicity and stronger resistance in mice to the development of a mammary tumor than to a smaller number (10(3) AdCa cells) of untreated viable adenocarcinoma cells. Cells treated with adenosine 3'5'-monophosphate accelerated tumor development.", "contents": "Modification of the immunologic properties of the cell surface. Living CF1 mouse-transplantable spontaneous mammary adenocarcinoma cells were modified with glutaraldehyde, formalin, 2,4,6-trinitrophenylate, Vibrio cholerae neurominidase, iodoacetate, heparin, histamine and adenosine 3'5'-monophosphate (cAMP), then used to immunize syngeneic CF1 mice. Animals immunized with the fixed (formalinized or glutaraldehyde fixed) neuraminidase-treated cells or the membrane of these cells, rejected two challenging doses of 10(8) viable unmodified adenocarcinoma cells. Animals immunized with adenocarcinoma cells treated with neuraminidase (170 IU/5x10(5) cells) or with the spontaneous adenocarcinoma-cell surface glycoprotein, rejected the first challenging dose but developed tumors and died on the second challenge with the viable untreated adenocarcinoma cells. Animals immunized with the adenocarcinoma cells pretreated with trinitrophenylate, glutaraldehyde or formalin, developed temporary resistance to the spontaneous mammary adenocarcinoma. Adenocarcinoma cells pretreated with NaF, iodoacetate, heparin, EDTA, Colchicine or histamine showed reduced oncogenicity and stronger resistance in mice to the development of a mammary tumor than to a smaller number (10(3) AdCa cells) of untreated viable adenocarcinoma cells. Cells treated with adenosine 3'5'-monophosphate accelerated tumor development."}
{"id": "PMID:24584", "title": "The persistent PHA-responsive population in the mouse thymus. II. Recirculatory characteristics and immunological properties.", "content": "Experiments were performed to ascertain whether the persistent PHA-responsive cell population found in mouse thymus grafts was capable both of localizing to peripheral lymphoid organs when deliberately injected into suitable recipient mice, and of responding to antigenic stimulation. It was shown that the persistent population could not be found in large numbers in recipient spleens or lymph nodes at late time after transfer. These cells could, however, be found in large numbers in the peripheral blood of recipients. Thus they appeared to be able to circulate in the blood but not be able to extravascularize in lymphoid organs. Since these cells did not localize to spleen or lymph nodes, it was not surprising to find that they did not respond to the skin sensitizing agent oxazolone in draining lymph nodes or spleen, or to histocompatibility antigens (graft-vs-host). When tested against allogeneic cells in vitro (mixed lymphocyte reaction), it was shown that the persistent population was over nine times less reactive than in its reactivity to PHA, when compared to the non-persistent population. The functional significance of these thymocyte populations is discussed.", "contents": "The persistent PHA-responsive population in the mouse thymus. II. Recirculatory characteristics and immunological properties. Experiments were performed to ascertain whether the persistent PHA-responsive cell population found in mouse thymus grafts was capable both of localizing to peripheral lymphoid organs when deliberately injected into suitable recipient mice, and of responding to antigenic stimulation. It was shown that the persistent population could not be found in large numbers in recipient spleens or lymph nodes at late time after transfer. These cells could, however, be found in large numbers in the peripheral blood of recipients. Thus they appeared to be able to circulate in the blood but not be able to extravascularize in lymphoid organs. Since these cells did not localize to spleen or lymph nodes, it was not surprising to find that they did not respond to the skin sensitizing agent oxazolone in draining lymph nodes or spleen, or to histocompatibility antigens (graft-vs-host). When tested against allogeneic cells in vitro (mixed lymphocyte reaction), it was shown that the persistent population was over nine times less reactive than in its reactivity to PHA, when compared to the non-persistent population. The functional significance of these thymocyte populations is discussed."}
{"id": "PMID:24585", "title": "Ther persistent PHA-responsive population in the mouse thymus. II. Recirculatory characteristics and immunological properties.", "content": "Experiments were performed to ascertain whether the persistent PHA-responsive cell population found in mouse thymus grafts was capable both of localizing to peripheral lymphoid organs when deliverately injected into suitable recipient mice, and of resonding to antigenic stimulation. It was shown that the persistent population could not be found in large numbers in recipient spleens or lymph nodes at late time after transfer. These cells could, however, be found in large numbers in the peripheral blood of recipients. Thus they appeared to be able to circulate in the blood but not able to extravascularize in lymphoid organs. Since these cells did not localize to spleen or lymph nodes, it was not surprising to find that they did not response to the skin sensitizing agent oxazolone in draining lymph nodes or spleen, or to histocompatibility antigens (graft-vs-host). When tested against allogeneic cells in vitro (mixed lymphocyte reaction), it was shown that the persistent population was over nine times less reactive than in its reactivity to PHA, when compared to the non-persistent population. The functional significance of these thymocyte populations is discussed.", "contents": "Ther persistent PHA-responsive population in the mouse thymus. II. Recirculatory characteristics and immunological properties. Experiments were performed to ascertain whether the persistent PHA-responsive cell population found in mouse thymus grafts was capable both of localizing to peripheral lymphoid organs when deliverately injected into suitable recipient mice, and of resonding to antigenic stimulation. It was shown that the persistent population could not be found in large numbers in recipient spleens or lymph nodes at late time after transfer. These cells could, however, be found in large numbers in the peripheral blood of recipients. Thus they appeared to be able to circulate in the blood but not able to extravascularize in lymphoid organs. Since these cells did not localize to spleen or lymph nodes, it was not surprising to find that they did not response to the skin sensitizing agent oxazolone in draining lymph nodes or spleen, or to histocompatibility antigens (graft-vs-host). When tested against allogeneic cells in vitro (mixed lymphocyte reaction), it was shown that the persistent population was over nine times less reactive than in its reactivity to PHA, when compared to the non-persistent population. The functional significance of these thymocyte populations is discussed."}
{"id": "PMID:24586", "title": "Cell transplantation into immunodeficient chicken embryos. Reconstituting capacity of cells from the yolk sac at different stages of development and from the liver, thymus, bursa of Fabricius, spleen and bone marrow of 15-day embryos.", "content": "Cyclophosphamide-treated 18-day-old chicken embryos were transplanted with histocompatible cells from the yolk sac at different stages of development and from the liver, thymus, bursa of Fabricius, spleen and bone marrow of 15-day-old-embryos. At the age of 36 days, the cell recipients were studied to determine the reconstitution capacity of the transplanted cells. The parameters used include the survival pattern, gain of body weight, antibody-forming capacity, response of peripheral blood lymphocytes to Con A, weight and microscopic morphology of the bursa of Fabricius, and weight of spleen and thymus. By all the criteria employed, only bursa cells were capable of a functional and morphological reconstitution of the recipient's humoral immune system. These data indicate that the role of the yolk sac as the first generator of prebursal stem cells remains questionable. In addition, these findings confirm the previous observations that, as a differentiation site of the B-cell lineage, the bursa of Fabricius precedes the bone marrow during ontogenetic development.", "contents": "Cell transplantation into immunodeficient chicken embryos. Reconstituting capacity of cells from the yolk sac at different stages of development and from the liver, thymus, bursa of Fabricius, spleen and bone marrow of 15-day embryos. Cyclophosphamide-treated 18-day-old chicken embryos were transplanted with histocompatible cells from the yolk sac at different stages of development and from the liver, thymus, bursa of Fabricius, spleen and bone marrow of 15-day-old-embryos. At the age of 36 days, the cell recipients were studied to determine the reconstitution capacity of the transplanted cells. The parameters used include the survival pattern, gain of body weight, antibody-forming capacity, response of peripheral blood lymphocytes to Con A, weight and microscopic morphology of the bursa of Fabricius, and weight of spleen and thymus. By all the criteria employed, only bursa cells were capable of a functional and morphological reconstitution of the recipient's humoral immune system. These data indicate that the role of the yolk sac as the first generator of prebursal stem cells remains questionable. In addition, these findings confirm the previous observations that, as a differentiation site of the B-cell lineage, the bursa of Fabricius precedes the bone marrow during ontogenetic development."}
{"id": "PMID:24590", "title": "Effects of fluoride on carbohydrate metabolism by washed cells of Streptococcus mutans grown at various pH values in a chemostat.", "content": "Streptococcus mutans Ingbritt was grown anaerobically in a chemostat, at a rate (mean generation time, 13 h) similar to that in dental plaque, in a complex medium with excess glucose and at pH values of 6.5, 6.0, and 5.5. The yield of cells was constant at pH 6.5 and 6.0 (2.00 mg/ml) but fell to 1.25 at pH 5.5; Y(glucose) was relatively constant under all conditions. Lactic acid was the major end product. Amino acid analysis of the culture supernatants indicated that growth was probably limited by the availability of cysteine. Cells were harvested and monitored for their capacity to produce acid from endogenous polysaccharide and exogenous sugars in the presence and absence of NaF, as well as for their glucose phosphoenolpyruvate (PEP)-phosphotransferase activity. Surprisingly, cells grown at pH 5.5 possessed two to three times more glycolytic activity, as measured by the rate of acid production, than cells grown at pH 6.5 and 6.0 when incubated in a washed suspension at constant pH with a sugar source. Furthermore, the cells grown at pH 5.5 were about twice as resistant to the effect of NaF in reducing the rate of acid production in this system. Fluoride inhibition could be reversed by increasing the pH of the system. Cells grown at all three pH values showed significant acid production from endogenous reserves, despite the fact that the glucoamylase-specific glycogen content of the cells dropped from 33% of the total carbohydrate during pH 6.5 growth to only 3% after growth at pH 6.0 and 6.5. Incubation of washed cells for 18 h in phosphate buffer resulted in the loss of 62% of the total carbohydrate, indicating that nonglycogen cellular polysaccharide was metabolized. A comparison of the fluoride effect on endogenous and exogenous metabolism under pH fall conditions showed that, with pH 6.5- and 6.0-grown cells, the inhibitor was more effective in the presence of an exogenous carbon source than in its absence. This effect was not seen with pH 5.5-grown cells. The decreased sensitivity of the pH 5.5-grown cells to fluoride was probably associated with the decreased glucose PEP-phosphotransferase activity (11%) in these cells compared with the activity of those grown at pH 6.5. This evidence supports the hypothesis that S. mutans possesses at least two glucose transport systems, one of which is relatively fluoride insensitive.", "contents": "Effects of fluoride on carbohydrate metabolism by washed cells of Streptococcus mutans grown at various pH values in a chemostat. Streptococcus mutans Ingbritt was grown anaerobically in a chemostat, at a rate (mean generation time, 13 h) similar to that in dental plaque, in a complex medium with excess glucose and at pH values of 6.5, 6.0, and 5.5. The yield of cells was constant at pH 6.5 and 6.0 (2.00 mg/ml) but fell to 1.25 at pH 5.5; Y(glucose) was relatively constant under all conditions. Lactic acid was the major end product. Amino acid analysis of the culture supernatants indicated that growth was probably limited by the availability of cysteine. Cells were harvested and monitored for their capacity to produce acid from endogenous polysaccharide and exogenous sugars in the presence and absence of NaF, as well as for their glucose phosphoenolpyruvate (PEP)-phosphotransferase activity. Surprisingly, cells grown at pH 5.5 possessed two to three times more glycolytic activity, as measured by the rate of acid production, than cells grown at pH 6.5 and 6.0 when incubated in a washed suspension at constant pH with a sugar source. Furthermore, the cells grown at pH 5.5 were about twice as resistant to the effect of NaF in reducing the rate of acid production in this system. Fluoride inhibition could be reversed by increasing the pH of the system. Cells grown at all three pH values showed significant acid production from endogenous reserves, despite the fact that the glucoamylase-specific glycogen content of the cells dropped from 33% of the total carbohydrate during pH 6.5 growth to only 3% after growth at pH 6.0 and 6.5. Incubation of washed cells for 18 h in phosphate buffer resulted in the loss of 62% of the total carbohydrate, indicating that nonglycogen cellular polysaccharide was metabolized. A comparison of the fluoride effect on endogenous and exogenous metabolism under pH fall conditions showed that, with pH 6.5- and 6.0-grown cells, the inhibitor was more effective in the presence of an exogenous carbon source than in its absence. This effect was not seen with pH 5.5-grown cells. The decreased sensitivity of the pH 5.5-grown cells to fluoride was probably associated with the decreased glucose PEP-phosphotransferase activity (11%) in these cells compared with the activity of those grown at pH 6.5. This evidence supports the hypothesis that S. mutans possesses at least two glucose transport systems, one of which is relatively fluoride insensitive."}
{"id": "PMID:24591", "title": "Observation of beta-hemolysis among three strains of Streptococcus mutans.", "content": "Streptococcus mutans is normally alpha- or gamma-hemolytic on blood agar plates. However, three recently isolated S. mutans strains were observed to elicit beta-hemolysis. The production and nature of a hemolytic substance were studied.", "contents": "Observation of beta-hemolysis among three strains of Streptococcus mutans. Streptococcus mutans is normally alpha- or gamma-hemolytic on blood agar plates. However, three recently isolated S. mutans strains were observed to elicit beta-hemolysis. The production and nature of a hemolytic substance were studied."}
{"id": "PMID:24592", "title": "Splenic foci of cytotoxic lymphocytes in a graft-versus-host reaction.", "content": "It has been established that cytotoxic lymphocytes are generated in discrete foci in the spleens of mice undergoing a graft-versus-host reaction. The foci segregated randomly in such spleens. 2.8 X 10(4) lymph node cells, 2.3 X 10(5) spleen cells and 2.7 X 10(6) thymus cells from CBA mice generated a mean of one focus in lethally irradiated (CBA X DBA)F1 recipient mice. Cytotoxic foci were detected when cytotoxicity was measured by two different cytotoxicity assays, the release of [51Cr]-sodium chromate from [51Cr]-labelled target cells and colony inhibition. The seeding efficiency of cytotoxic focus-forming cells has been estimated at 19%.", "contents": "Splenic foci of cytotoxic lymphocytes in a graft-versus-host reaction. It has been established that cytotoxic lymphocytes are generated in discrete foci in the spleens of mice undergoing a graft-versus-host reaction. The foci segregated randomly in such spleens. 2.8 X 10(4) lymph node cells, 2.3 X 10(5) spleen cells and 2.7 X 10(6) thymus cells from CBA mice generated a mean of one focus in lethally irradiated (CBA X DBA)F1 recipient mice. Cytotoxic foci were detected when cytotoxicity was measured by two different cytotoxicity assays, the release of [51Cr]-sodium chromate from [51Cr]-labelled target cells and colony inhibition. The seeding efficiency of cytotoxic focus-forming cells has been estimated at 19%."}
{"id": "PMID:24595", "title": "Decrease of peripheral resistance after acute intravenous application of a new beta-receptor blocking agents, bufuralol HCl.", "content": "The hemodynamic effects of a new beta-receptor blocking agent, bufuraolo HCl, were compared with those of pindolol. Contrary to pindolol, bufuralol HCl induces a decrease of the peripheral resistance immediately. Under exercise conditions, the peripheral resistance increases under pindolol whereas it remains constant under bufuralol HCl in spite of reduced cardiac output. As an explanation, an effect of bufuralol HCl on peripheral resistance is discussed which might be independent of the beta-receptor blocking effects in the periphery.", "contents": "Decrease of peripheral resistance after acute intravenous application of a new beta-receptor blocking agents, bufuralol HCl. The hemodynamic effects of a new beta-receptor blocking agent, bufuraolo HCl, were compared with those of pindolol. Contrary to pindolol, bufuralol HCl induces a decrease of the peripheral resistance immediately. Under exercise conditions, the peripheral resistance increases under pindolol whereas it remains constant under bufuralol HCl in spite of reduced cardiac output. As an explanation, an effect of bufuralol HCl on peripheral resistance is discussed which might be independent of the beta-receptor blocking effects in the periphery."}
{"id": "PMID:24596", "title": "Cefazolin in the treatment of pneumonia.", "content": "Cefazolin is a semi-synthetic derivative of cephalosporin C that has a lower cross-immunogenicity with penicillins than do the other cephalosporins. This agent was evaluated as an alternative to penicillin in the therapy of patients with pneumococcal pneumonia. Thirty patient were treated with cefazolin, most receiving 125 or 250 mg IM every 12 hours for 5-10 days. Satisfactory clinical responses were obtained in 29 of these 30 patients, and none complained of pain following IM injections. Three patients developed eosinophilia while receiving cefazolin, and one of these also had a maculopapular eruption that may have been an allergic reaction to cefazolin. Serum levels of cefazolin were measured at 1, 6, and 12 hours after administration. Susceptibilities of 100 isolates of Streptococcus pneumoniae, including these patients' organisms, were determined by broth dilution. Both cefazolin and cephalothin were bactericidal for all 100 isolates at concentrations of 2 microgram/ml or less. Cefazolin appears to be an entirely adequate alternative to penicillin for the therapy of pneumococcalpneumonia. This agent is effective in low dosages, and adequate serum levels are maintained for long periods of time, permitting twice-daily administration.", "contents": "Cefazolin in the treatment of pneumonia. Cefazolin is a semi-synthetic derivative of cephalosporin C that has a lower cross-immunogenicity with penicillins than do the other cephalosporins. This agent was evaluated as an alternative to penicillin in the therapy of patients with pneumococcal pneumonia. Thirty patient were treated with cefazolin, most receiving 125 or 250 mg IM every 12 hours for 5-10 days. Satisfactory clinical responses were obtained in 29 of these 30 patients, and none complained of pain following IM injections. Three patients developed eosinophilia while receiving cefazolin, and one of these also had a maculopapular eruption that may have been an allergic reaction to cefazolin. Serum levels of cefazolin were measured at 1, 6, and 12 hours after administration. Susceptibilities of 100 isolates of Streptococcus pneumoniae, including these patients' organisms, were determined by broth dilution. Both cefazolin and cephalothin were bactericidal for all 100 isolates at concentrations of 2 microgram/ml or less. Cefazolin appears to be an entirely adequate alternative to penicillin for the therapy of pneumococcalpneumonia. This agent is effective in low dosages, and adequate serum levels are maintained for long periods of time, permitting twice-daily administration."}
{"id": "PMID:24597", "title": "Comparative potency of intravenous penbutolol and propranolol in man.", "content": "A study on the comparative potency of intravenously administered penbutolol, a new non-selective beta adrenoceptor antagonist, on the resting and post-exercise heart rate and rate-pressure product was carried out in 5 normal human subjects. The effects produced by 0.1, 0.2 and 0.3 mg of penbutolol and of 0.025 mg/kg (mean dose 1.28 mg) of propranolol was recorded. The dose of penbutolol producing an effect equivalent to that of propranolol was calculating from the log dose-response curve of penbutolol. In these tests, penbutolol was 7.90 and 7.66 times more potent than propranolol on a weight to weight basis. Penbutolol was well tolerated and no side-effects were observed.", "contents": "Comparative potency of intravenous penbutolol and propranolol in man. A study on the comparative potency of intravenously administered penbutolol, a new non-selective beta adrenoceptor antagonist, on the resting and post-exercise heart rate and rate-pressure product was carried out in 5 normal human subjects. The effects produced by 0.1, 0.2 and 0.3 mg of penbutolol and of 0.025 mg/kg (mean dose 1.28 mg) of propranolol was recorded. The dose of penbutolol producing an effect equivalent to that of propranolol was calculating from the log dose-response curve of penbutolol. In these tests, penbutolol was 7.90 and 7.66 times more potent than propranolol on a weight to weight basis. Penbutolol was well tolerated and no side-effects were observed."}
{"id": "PMID:24598", "title": "Scanning electron microscopy of human female reproductive tract and amniotic fluid cells.", "content": "Scanning electron microscopy was used to examine surface ultrastructural characteristics of cells of the epithelium of female reproductive tract, cervical mucus, and amniotic fluid cells. The female epithelium undergoes hormone-dependent cyclical morphological alterations in cell shape, apical microvilli, ciliation, and secretory patterns. The frequency distribution of ciliated cells varies in different parts of the female reproductive tract and different segments of the same organ. In the endocervix, a few ciliated cells are randomly distributed. The density of ciliated cells is variable in several areas of the endometrium. The sparse distribution of ciliated cells in the central portion of the uterine wall may indicate a possible implantation site. According to surface ultrastructure of cells, three segments are noted in the uterotubal junction: cornual endometrium, interstitial tubal epithelium, and transitional area. The vaginal epithelium is made of flat polygonal cells with interdigitating borders and a fine interlacing network of microridges. After the menopause, the microridge pattern and distinct cell borders are lost or severely modified. Two types of fibrous structures can be found in cervical mucus: a) microfibrils that vary in diameter from 500 to 1,500 A and from bundles or networks, and b) long, thick fibers that vary in diameter from 0.5 to 5 micrometer run parallel to each other, and appear to be made up of microfibrils. Amniotic fluid cells, derived from amniotic epithelium and fetal ectoderm, consist of non-nucleated and nucleated cells with extensive microplicae.", "contents": "Scanning electron microscopy of human female reproductive tract and amniotic fluid cells. Scanning electron microscopy was used to examine surface ultrastructural characteristics of cells of the epithelium of female reproductive tract, cervical mucus, and amniotic fluid cells. The female epithelium undergoes hormone-dependent cyclical morphological alterations in cell shape, apical microvilli, ciliation, and secretory patterns. The frequency distribution of ciliated cells varies in different parts of the female reproductive tract and different segments of the same organ. In the endocervix, a few ciliated cells are randomly distributed. The density of ciliated cells is variable in several areas of the endometrium. The sparse distribution of ciliated cells in the central portion of the uterine wall may indicate a possible implantation site. According to surface ultrastructure of cells, three segments are noted in the uterotubal junction: cornual endometrium, interstitial tubal epithelium, and transitional area. The vaginal epithelium is made of flat polygonal cells with interdigitating borders and a fine interlacing network of microridges. After the menopause, the microridge pattern and distinct cell borders are lost or severely modified. Two types of fibrous structures can be found in cervical mucus: a) microfibrils that vary in diameter from 500 to 1,500 A and from bundles or networks, and b) long, thick fibers that vary in diameter from 0.5 to 5 micrometer run parallel to each other, and appear to be made up of microfibrils. Amniotic fluid cells, derived from amniotic epithelium and fetal ectoderm, consist of non-nucleated and nucleated cells with extensive microplicae."}
{"id": "PMID:24599", "title": "Variation in human semen viscoelastic properties with respect to time post ejaculation and frequency of ejaculation.", "content": "The present study concerns the rheological characterization of the coagulation-liquefaction process of human semen. Results obtained using a multiple point capillary viscometer reveal marked variations in the elasticity and viscosity of an individual's semen with time immediately following ejaculation and frequency of ejaculation. Similarity among all cases examined for each material property is revealed by relating times post ejaculation to semen liquefaction time, thereby coupling liquefaction time with specific material property values. Further, the final state of liquefied semen is found to be characterized by Newtonian behavior (mean absolute viscosity = 3.37 centipoise). The semen's liquefaction time and ejaculate volume are determined to be functions of the frequency of ejaculation. Steady state ejaculate volume is found to decrease linearly with increasing ejaculation frequency, thereby providing a measure of glandular secretory rate. When collectively considered, these findings provide possible means for monitoring an individual's glandular behavior over an extended period of time and comparing such behavior to established standards.", "contents": "Variation in human semen viscoelastic properties with respect to time post ejaculation and frequency of ejaculation. The present study concerns the rheological characterization of the coagulation-liquefaction process of human semen. Results obtained using a multiple point capillary viscometer reveal marked variations in the elasticity and viscosity of an individual's semen with time immediately following ejaculation and frequency of ejaculation. Similarity among all cases examined for each material property is revealed by relating times post ejaculation to semen liquefaction time, thereby coupling liquefaction time with specific material property values. Further, the final state of liquefied semen is found to be characterized by Newtonian behavior (mean absolute viscosity = 3.37 centipoise). The semen's liquefaction time and ejaculate volume are determined to be functions of the frequency of ejaculation. Steady state ejaculate volume is found to decrease linearly with increasing ejaculation frequency, thereby providing a measure of glandular secretory rate. When collectively considered, these findings provide possible means for monitoring an individual's glandular behavior over an extended period of time and comparing such behavior to established standards."}
{"id": "PMID:24600", "title": "Ovulation induction with human menopausal gonadotrophins: an evaluation of a variable daily dosage regimen.", "content": "Human menopausal gonadotrophins (HMG) were used together with human chorionic gonadotrophin (HCG) in 19 women and 39 treatment cycles in an attempt to induce ovulation. Daily 24 hours urinary total estrogen excretion rates were measured and HMG daily dosage was varied according to levels obtained. HCG injections were timed to coincide with an estimated urinary total estrogen excretion rate of 100-150 g per 24 hours. Thirty-one ovulatory cycles occurred (79%) and there were nine pregnancies (23%) of which five were multiple. Eleven cycles were complicated by hyperstimulation (25.6%) of which six were severe. The variable HMG dosage regimen was found to offer no advantages when compared with our standard daily dosage regimen. A rapid rise of estrogen excretion occurred in over 80% of hyperstimulation cycles, including all severe ones, and it was found that this rise could occur after the last dosage of HMG had been given. Because of this, it is proposed that HCG injections be delayed until 48 hours after the last injection of HMG. The finding of a value for the last available 24 hour urinary total estrogen excretion of less than 150 microgram can be taken as an indicator that hyperstimulation is unlikely to occur, and that HCG can safely be given. No indication was found that such a procedure would diminish ovulation or pregnancy rates.", "contents": "Ovulation induction with human menopausal gonadotrophins: an evaluation of a variable daily dosage regimen. Human menopausal gonadotrophins (HMG) were used together with human chorionic gonadotrophin (HCG) in 19 women and 39 treatment cycles in an attempt to induce ovulation. Daily 24 hours urinary total estrogen excretion rates were measured and HMG daily dosage was varied according to levels obtained. HCG injections were timed to coincide with an estimated urinary total estrogen excretion rate of 100-150 g per 24 hours. Thirty-one ovulatory cycles occurred (79%) and there were nine pregnancies (23%) of which five were multiple. Eleven cycles were complicated by hyperstimulation (25.6%) of which six were severe. The variable HMG dosage regimen was found to offer no advantages when compared with our standard daily dosage regimen. A rapid rise of estrogen excretion occurred in over 80% of hyperstimulation cycles, including all severe ones, and it was found that this rise could occur after the last dosage of HMG had been given. Because of this, it is proposed that HCG injections be delayed until 48 hours after the last injection of HMG. The finding of a value for the last available 24 hour urinary total estrogen excretion of less than 150 microgram can be taken as an indicator that hyperstimulation is unlikely to occur, and that HCG can safely be given. No indication was found that such a procedure would diminish ovulation or pregnancy rates."}
{"id": "PMID:24601", "title": "Ovulation timing by a radioreceptor assay for human luteinizing hormone.", "content": "Since predetermination of ovulation would be helpful in treatment of sterility, a quick, sensitive, and specific radioreceptor assay (RRA) for measurement of actual LH concentrations in human serum has been developed. Using partially purified membrane receptors from bovine testes, our assay system enabled precise measurement of LH within 4 hours. The detection limit of the present method is 0.78 ng LER 960/ml serum. The method was used to detect ovulation during four observation cycles each in eleven women who were undergoing treatment for infertility, such as recommended intercourse or artificial insemination because of reduced fertility of their husbands. In all women ovulations could be predicted by LH surge and were verified by laparoscopy within 36 hours. Insemination was carried out at the time of the characteristic increase of LH values around mid-cycle. Pregnancy occurred in three women during the observation period.", "contents": "Ovulation timing by a radioreceptor assay for human luteinizing hormone. Since predetermination of ovulation would be helpful in treatment of sterility, a quick, sensitive, and specific radioreceptor assay (RRA) for measurement of actual LH concentrations in human serum has been developed. Using partially purified membrane receptors from bovine testes, our assay system enabled precise measurement of LH within 4 hours. The detection limit of the present method is 0.78 ng LER 960/ml serum. The method was used to detect ovulation during four observation cycles each in eleven women who were undergoing treatment for infertility, such as recommended intercourse or artificial insemination because of reduced fertility of their husbands. In all women ovulations could be predicted by LH surge and were verified by laparoscopy within 36 hours. Insemination was carried out at the time of the characteristic increase of LH values around mid-cycle. Pregnancy occurred in three women during the observation period."}
{"id": "PMID:24602", "title": "Endocoagulation: a new and completely safe medical current for sterilization.", "content": "Tubal sterilization via pelviscopy with low current represents a unique method: the risk of high-frequency is thereby eliminated, and the application of the Crocodile-Forceps is relatively simple. The mouth of the Crocodile-Forceps grasps the tube under pelviscopic control. Tubal coagulation succeeds under electronic control at 100 degrees C and the area of coagulation measures 6-8 mm in length. In case additional separation of the tube is desired it may be performed bloodlessly with a scissor-like movement. The Crocodile-Clamp is electronically monitored by the \"Tube-Coagulator\" or the universal endoscopic \"Endo-Coagulator.\" Since 1973 964 tubal coagulations by means of cutting have been performed without postoperative hemorrhage or other complications (pregnancy rate 0).", "contents": "Endocoagulation: a new and completely safe medical current for sterilization. Tubal sterilization via pelviscopy with low current represents a unique method: the risk of high-frequency is thereby eliminated, and the application of the Crocodile-Forceps is relatively simple. The mouth of the Crocodile-Forceps grasps the tube under pelviscopic control. Tubal coagulation succeeds under electronic control at 100 degrees C and the area of coagulation measures 6-8 mm in length. In case additional separation of the tube is desired it may be performed bloodlessly with a scissor-like movement. The Crocodile-Clamp is electronically monitored by the \"Tube-Coagulator\" or the universal endoscopic \"Endo-Coagulator.\" Since 1973 964 tubal coagulations by means of cutting have been performed without postoperative hemorrhage or other complications (pregnancy rate 0)."}
{"id": "PMID:24604", "title": "In vivo cholinergic stimulation of the rabbit oviductal musculature.", "content": "The in vivo activity of the rabbit oviductal musculature was evaluated in terms of constant rate perfusion resistance. Efforts to compare adrenergic and cholinergic stimulation showed that both pilocarpine and bethanechol chloride increased muscular activity 17-24% of that induced by epinephrine. The cholinergic stimulatory effect was reduced by adrenergic alpha blockade and completely abolished by cholinergic blockade or norepinephrine depletion. The data suggest that cholinergic stimulation of the tubal musculature is mediated, in part, via postganglionic adrenergic nerve fibers. It would appear that the oviductal musculature is not a primary target tissue for systemically administered autonomic agonists or antagonists.", "contents": "In vivo cholinergic stimulation of the rabbit oviductal musculature. The in vivo activity of the rabbit oviductal musculature was evaluated in terms of constant rate perfusion resistance. Efforts to compare adrenergic and cholinergic stimulation showed that both pilocarpine and bethanechol chloride increased muscular activity 17-24% of that induced by epinephrine. The cholinergic stimulatory effect was reduced by adrenergic alpha blockade and completely abolished by cholinergic blockade or norepinephrine depletion. The data suggest that cholinergic stimulation of the tubal musculature is mediated, in part, via postganglionic adrenergic nerve fibers. It would appear that the oviductal musculature is not a primary target tissue for systemically administered autonomic agonists or antagonists."}
{"id": "PMID:24605", "title": "Seminal proteins in patients with agglomerations of spermatozoa.", "content": "Seminal proteins (IgA, IgG, albumin) were measured in normozoospermic patients and in patients with normozoospermia associated with agglomerations of spermatozoa. The type of agglomeration was not taken into account. A slight yet significant increase in seminal IgA was detected in patients with agglomerations whereas the other proteins remained unchanged. By testing seminal plasma against C1q by double diffusion it was shown that many patients of both groups had nonimmune C1q precipitins. The significance of such precipitins in semen is not known.", "contents": "Seminal proteins in patients with agglomerations of spermatozoa. Seminal proteins (IgA, IgG, albumin) were measured in normozoospermic patients and in patients with normozoospermia associated with agglomerations of spermatozoa. The type of agglomeration was not taken into account. A slight yet significant increase in seminal IgA was detected in patients with agglomerations whereas the other proteins remained unchanged. By testing seminal plasma against C1q by double diffusion it was shown that many patients of both groups had nonimmune C1q precipitins. The significance of such precipitins in semen is not known."}
{"id": "PMID:24606", "title": "Decrease of sperm antibody titer in males, and conception after treatment of chronic prostatitis.", "content": "Although autoimmunization to spermatozoa is a cause of male infertility, the cause of antibody formation is unknown in most cases. It has been shown that the titer is usually unchanged for as much as 16 years in the same individual. Trials to reduce the titer with varying methods have not been successful. A new possibility of treatment was indicated by the finding of a higher incidence of prostatitis in men with sperm antibodies than in a control group. Following treatment of prostatitis we observed a reduction of the antibody titer in eight cases. In five cases the cervical mucus penetrating capacity of the spermatozoa improved, and conception occurred.", "contents": "Decrease of sperm antibody titer in males, and conception after treatment of chronic prostatitis. Although autoimmunization to spermatozoa is a cause of male infertility, the cause of antibody formation is unknown in most cases. It has been shown that the titer is usually unchanged for as much as 16 years in the same individual. Trials to reduce the titer with varying methods have not been successful. A new possibility of treatment was indicated by the finding of a higher incidence of prostatitis in men with sperm antibodies than in a control group. Following treatment of prostatitis we observed a reduction of the antibody titer in eight cases. In five cases the cervical mucus penetrating capacity of the spermatozoa improved, and conception occurred."}
{"id": "PMID:24607", "title": "pH controlled diazo coupling of aldolase. Selective formation of diazothioether chromophores and retention of enzyme activity.", "content": "pH Conditions have been found which achieve selective reaction of diazotized p-amino benzoate with cysteine residues of rabbit muscle aldolase. The difference in reactivity of the two sulphydryl groups involved, (Cys--237 and Cys--287) permits one to form either four or eight diazothioethers on the tetrameric enzyme and obtain a homogeneous protein. In both cases the enzyme became slightly more active in the fructose-1, 6-bisphosphate cleavage, the KM value being retained. The results have been discussed with regard to chemically modifying an enzyme to change its physical, chemical and immunological properties, whilst leaving the catalytical activity unmodified.", "contents": "pH controlled diazo coupling of aldolase. Selective formation of diazothioether chromophores and retention of enzyme activity. pH Conditions have been found which achieve selective reaction of diazotized p-amino benzoate with cysteine residues of rabbit muscle aldolase. The difference in reactivity of the two sulphydryl groups involved, (Cys--237 and Cys--287) permits one to form either four or eight diazothioethers on the tetrameric enzyme and obtain a homogeneous protein. In both cases the enzyme became slightly more active in the fructose-1, 6-bisphosphate cleavage, the KM value being retained. The results have been discussed with regard to chemically modifying an enzyme to change its physical, chemical and immunological properties, whilst leaving the catalytical activity unmodified."}
{"id": "PMID:24610", "title": "The measurement of histochemically-stained NADP-dependent isocitrate dehydrogenase in the sebaceous glands of hairless hamster.", "content": "The effect of substrate, co-factor and Nitroblue Tetrazolium concentration on the production of formazan by the action of NADP-dependent isocitrate dehydrogenase was studied in the sebaceous glands of the hairless hamster. The measurement (in average optical density units per unit area) of formazan in histochemically stained skin sections was carried out by television scanning microdensitometry (Quantimet 720D). Having established optimal conditions for this enzyme, a second study was carried out to determine the effect of different power objectives and wide-band wavelength light instead of white light on the average optical density per unit area, recorded by the instrument, of the formazan produced in a defined number of sebaceous glands in a single skin section. It was found that there was no difference in the average optical density per unit area recorded by the instrument at different power objectives and a peak value of average optical density per unit area could be obtained using a K4 or a K5 Balzer filter (550-650 nm).", "contents": "The measurement of histochemically-stained NADP-dependent isocitrate dehydrogenase in the sebaceous glands of hairless hamster. The effect of substrate, co-factor and Nitroblue Tetrazolium concentration on the production of formazan by the action of NADP-dependent isocitrate dehydrogenase was studied in the sebaceous glands of the hairless hamster. The measurement (in average optical density units per unit area) of formazan in histochemically stained skin sections was carried out by television scanning microdensitometry (Quantimet 720D). Having established optimal conditions for this enzyme, a second study was carried out to determine the effect of different power objectives and wide-band wavelength light instead of white light on the average optical density per unit area, recorded by the instrument, of the formazan produced in a defined number of sebaceous glands in a single skin section. It was found that there was no difference in the average optical density per unit area recorded by the instrument at different power objectives and a peak value of average optical density per unit area could be obtained using a K4 or a K5 Balzer filter (550-650 nm)."}
{"id": "PMID:24609", "title": "A procedure for the assay of DNA damage in mammalian cells by alkaline elution and microfluorometric DNA determination.", "content": "The microfluorimetric assay of Kissane and Robins (J. Biol. Chem. 233, 184-188, 1958) has been modified to monitor DNA content in alkaline elution fractions. The elution profiles of DNA from treated and control cultured cells demonstrated a good correlation whether DNA in the elution fractions was determined by the fluorometric method or by measuring its radioactivity. The DNA recovery was of about 80% and the measured material was DNase digestible.", "contents": "A procedure for the assay of DNA damage in mammalian cells by alkaline elution and microfluorometric DNA determination. The microfluorimetric assay of Kissane and Robins (J. Biol. Chem. 233, 184-188, 1958) has been modified to monitor DNA content in alkaline elution fractions. The elution profiles of DNA from treated and control cultured cells demonstrated a good correlation whether DNA in the elution fractions was determined by the fluorometric method or by measuring its radioactivity. The DNA recovery was of about 80% and the measured material was DNase digestible."}
{"id": "PMID:24613", "title": "Binding of aminoglycoside antibiotics to acidic mucopolysaccharides.", "content": "Binding of aminoglycoside antibiotics to acidic mucopolysaccharides has been studied by means of physicochemical methods. Reactivity was affected markedly by the ionic environment , e.g. pH and ionic strength of the medium, the concentrations and the molar ratios of the constituents. The ionic character of binding was further confirmed by gel chromatography. The reduction of metachromasis by an aminoglycoside was also observed. Their affinity is correlated with localization of the aminoglycosides in vivo. According to reactivity, the following descending order of affinity was obtained for each family: neomycin, gentamicin, sagamicin, kanamycin and streptomycin; heparin, chondroitin sulfate and hyaluronic acid. This sequence of aminoglycosides corresponds to the extent of oto-, nephro- and neuro-(acute)toxicity, suggesting that their affinity for acidic mucopolysaccharides contribute to their tissue toxicity.", "contents": "Binding of aminoglycoside antibiotics to acidic mucopolysaccharides. Binding of aminoglycoside antibiotics to acidic mucopolysaccharides has been studied by means of physicochemical methods. Reactivity was affected markedly by the ionic environment , e.g. pH and ionic strength of the medium, the concentrations and the molar ratios of the constituents. The ionic character of binding was further confirmed by gel chromatography. The reduction of metachromasis by an aminoglycoside was also observed. Their affinity is correlated with localization of the aminoglycosides in vivo. According to reactivity, the following descending order of affinity was obtained for each family: neomycin, gentamicin, sagamicin, kanamycin and streptomycin; heparin, chondroitin sulfate and hyaluronic acid. This sequence of aminoglycosides corresponds to the extent of oto-, nephro- and neuro-(acute)toxicity, suggesting that their affinity for acidic mucopolysaccharides contribute to their tissue toxicity."}
{"id": "PMID:24614", "title": "Fluphenazine decanoate vs oral antipsychotics: a comparison of their effectiveness in the treatment of schizophrenia as measured by a reduction in hospital readmissions.", "content": "A significant number of chronic psychotic patients are readmitted to state mental hospitals each year due in large part to their inability or unwillingness to continue taking antipsychotic medication on a voluntary basis. This paper describes an ex post facto study comparing the effectiveness of fluphenazine decanoate, a long acting antipsychotic medication, with a variety of oral antipsychotics in reducing the number of readmissions of two groups of chronic psychotic patients to a state operated mental health facility. The results demonstrated that a group of 61 patients receiving fluphenazine decanoate had signigicantly fewer readmissions during the one year study period than did a comparison group on oral antipsychotics. The findings indicate that long acting antipsychotic medication, as part of an intensive outpatient treatment program, strongly militates against the tendency of chronic psychotic patients to discontinue treatment.", "contents": "Fluphenazine decanoate vs oral antipsychotics: a comparison of their effectiveness in the treatment of schizophrenia as measured by a reduction in hospital readmissions. A significant number of chronic psychotic patients are readmitted to state mental hospitals each year due in large part to their inability or unwillingness to continue taking antipsychotic medication on a voluntary basis. This paper describes an ex post facto study comparing the effectiveness of fluphenazine decanoate, a long acting antipsychotic medication, with a variety of oral antipsychotics in reducing the number of readmissions of two groups of chronic psychotic patients to a state operated mental health facility. The results demonstrated that a group of 61 patients receiving fluphenazine decanoate had signigicantly fewer readmissions during the one year study period than did a comparison group on oral antipsychotics. The findings indicate that long acting antipsychotic medication, as part of an intensive outpatient treatment program, strongly militates against the tendency of chronic psychotic patients to discontinue treatment."}
{"id": "PMID:24615", "title": "Heal illness syndrome and lithium intoxication.", "content": "This paper reviews heat illness syndrome and lithium intoxication and shows striking similarities in symptoms, predisposing factors, and physiology of both conditions. It is speculated that there is a common underlying mechanism present to account for this.", "contents": "Heal illness syndrome and lithium intoxication. This paper reviews heat illness syndrome and lithium intoxication and shows striking similarities in symptoms, predisposing factors, and physiology of both conditions. It is speculated that there is a common underlying mechanism present to account for this."}
{"id": "PMID:24616", "title": "New approach to the rehabilitation of the hard core drug addict (heroin methadone addicts) a pilot community study.", "content": "The limitation of the methadone maintenance program has pressed for a re-evaluation of our understanding of the underlying causes of addiction. Apparently, one of theunderlying causes or end result produced by the drug itself is that of depression. It explains why the addicts try to maintain to the maximum, the euphoric state and are unwilling to rehabilitate. A pilot study was conducted for the treatment of ex-methadone addicts with large dosages of antidepressants and anxiolytics. Out of 117 ex-methadone and soft drug addicts treated with antidepressants and anxiolytics, 46% ex-methadone and 46.3% soft drug abusers failed to become abstinent. The failures were basically related to the management of treatment. The study suggests a possibility for detoxification from methadone and control of relapse by antidepressants and anxiolytics.", "contents": "New approach to the rehabilitation of the hard core drug addict (heroin methadone addicts) a pilot community study. The limitation of the methadone maintenance program has pressed for a re-evaluation of our understanding of the underlying causes of addiction. Apparently, one of theunderlying causes or end result produced by the drug itself is that of depression. It explains why the addicts try to maintain to the maximum, the euphoric state and are unwilling to rehabilitate. A pilot study was conducted for the treatment of ex-methadone addicts with large dosages of antidepressants and anxiolytics. Out of 117 ex-methadone and soft drug addicts treated with antidepressants and anxiolytics, 46% ex-methadone and 46.3% soft drug abusers failed to become abstinent. The failures were basically related to the management of treatment. The study suggests a possibility for detoxification from methadone and control of relapse by antidepressants and anxiolytics."}
{"id": "PMID:24617", "title": "Metropolitan jail psychiatric clinic: a year's experience.", "content": "The behavioral, demographic and psychiatric characteristics of 524 inmates examined over a one year period in a metropolitan jail psychiatric treatment clinic are described. The psychiatric problems were sufficiently acute that over one-third of all patients were examined and treated within 24 hours of booking. Two psychiatric syndrome and intervention profiles emerged. The most commonly seen were misdemeanants, with psychotic illnesses who required long term antipsychotic medications and close contact with community treatment resources. Situational reactions with suicidal ideation in patients with character disorder diagnoses were seen less frequently. They were treated with short term anti-anxiety medications and environmental manipulation.", "contents": "Metropolitan jail psychiatric clinic: a year's experience. The behavioral, demographic and psychiatric characteristics of 524 inmates examined over a one year period in a metropolitan jail psychiatric treatment clinic are described. The psychiatric problems were sufficiently acute that over one-third of all patients were examined and treated within 24 hours of booking. Two psychiatric syndrome and intervention profiles emerged. The most commonly seen were misdemeanants, with psychotic illnesses who required long term antipsychotic medications and close contact with community treatment resources. Situational reactions with suicidal ideation in patients with character disorder diagnoses were seen less frequently. They were treated with short term anti-anxiety medications and environmental manipulation."}
{"id": "PMID:24618", "title": "The use of benzodiazepines in prison populations.", "content": "Experience with the use of tranquilizing drugs in the control of anxiety and in attempts at behavior modification, prompted a controlled study in the use of the benzodiazepines at the Utah state prison. It appeared that the benefits derived from the administration of these drugs in prisoner control were nearly outweighed by the frequent appearance of paradoxical rage reactions and increase in hostility and aggressive tendencies in these individuals. A double blind, cohort, prospective, randomized study was set up comparing Valium and Serax in their antianxiety qualities and their tendency to produce increased aggression and paradoxical rage reactions. Guidelines are proposed for the use of benzodiazepines and Serax is suggested as a superior drug to Valium for this purpose if indeed a tranquilizer of this type is indicated.", "contents": "The use of benzodiazepines in prison populations. Experience with the use of tranquilizing drugs in the control of anxiety and in attempts at behavior modification, prompted a controlled study in the use of the benzodiazepines at the Utah state prison. It appeared that the benefits derived from the administration of these drugs in prisoner control were nearly outweighed by the frequent appearance of paradoxical rage reactions and increase in hostility and aggressive tendencies in these individuals. A double blind, cohort, prospective, randomized study was set up comparing Valium and Serax in their antianxiety qualities and their tendency to produce increased aggression and paradoxical rage reactions. Guidelines are proposed for the use of benzodiazepines and Serax is suggested as a superior drug to Valium for this purpose if indeed a tranquilizer of this type is indicated."}
{"id": "PMID:24619", "title": "A pharmacological and theoretical comparison of high and low potency neuroleptics.", "content": "Side effects of high and low potency neuroleptics are contrasted. Low potency drugs are more likely to cause central, autonomic and peripheral side effects of all types with the exception of extrapyramidal symptoms. The tendency to produce tardive dyskinesia cannot be compared as relevant data do not currently exist. Greater affinity for the dopamine receptor and twenty to seventy-fold greater milligram and molar potency are advanced as arguments for greater specificity of high potency drugs in the treatment of psychoses. It is proposed that the high potency neuroleptics might be considered the drugs of choice in the treatment of schizophrenia and schizophreniform psychoses.", "contents": "A pharmacological and theoretical comparison of high and low potency neuroleptics. Side effects of high and low potency neuroleptics are contrasted. Low potency drugs are more likely to cause central, autonomic and peripheral side effects of all types with the exception of extrapyramidal symptoms. The tendency to produce tardive dyskinesia cannot be compared as relevant data do not currently exist. Greater affinity for the dopamine receptor and twenty to seventy-fold greater milligram and molar potency are advanced as arguments for greater specificity of high potency drugs in the treatment of psychoses. It is proposed that the high potency neuroleptics might be considered the drugs of choice in the treatment of schizophrenia and schizophreniform psychoses."}
{"id": "PMID:24622", "title": "Immunochemical study on the pathway of electron flow in reduced nicotinamide adenine dinucleotide-dependent microsomal lipid peroxidation.", "content": "NADH could support the lipid peroxidation of rat liver microsomes in the presence of ferric ions chelated by ADP(ADP-Fe). The reaction had a broad pH optimum (pH 5.8--7.4) and was more active in the acidic pH range. Antibodies to NADH-cytochrome b5 reductase [EC 1.6.2.2] and cytochrome b5 inhibited NADH-dependent lipid peroxidation in the presence of ADP-Fe, whereas the antibody against NADPH-cytochrome c reductase [EC 1.6.2.4] showed no inhibition. These oberservations suggest that the electron from NADH was supplied to the lipid peroxidation reaction via NADH-cytochrome b5 reductase and cytochrome b5. On the other hand, NADPH-supported lipid peroxidation was strongly inhibited by the antibody against NADPH-cytochrome c reductase, confirming the participation of this this flavoprotein in the NADPH-dependent reaction. In the presence of both ADP-Fe and ferric ions chelated by EDTA(EDTA-Fe), NADH-dependent lipid peroxidation was highly stimulated up to the level of the NADPH-dependent reaction. In this case, the antibody against cytochrome b5 could not inhibit the reaction, while the antibody against NADH-cytochrome b5 reductase did inhibit it, suggesting the direct transfer of electrons from NADH-cytochrome b5 reductase to EDTA-Fe complex.", "contents": "Immunochemical study on the pathway of electron flow in reduced nicotinamide adenine dinucleotide-dependent microsomal lipid peroxidation. NADH could support the lipid peroxidation of rat liver microsomes in the presence of ferric ions chelated by ADP(ADP-Fe). The reaction had a broad pH optimum (pH 5.8--7.4) and was more active in the acidic pH range. Antibodies to NADH-cytochrome b5 reductase [EC 1.6.2.2] and cytochrome b5 inhibited NADH-dependent lipid peroxidation in the presence of ADP-Fe, whereas the antibody against NADPH-cytochrome c reductase [EC 1.6.2.4] showed no inhibition. These oberservations suggest that the electron from NADH was supplied to the lipid peroxidation reaction via NADH-cytochrome b5 reductase and cytochrome b5. On the other hand, NADPH-supported lipid peroxidation was strongly inhibited by the antibody against NADPH-cytochrome c reductase, confirming the participation of this this flavoprotein in the NADPH-dependent reaction. In the presence of both ADP-Fe and ferric ions chelated by EDTA(EDTA-Fe), NADH-dependent lipid peroxidation was highly stimulated up to the level of the NADPH-dependent reaction. In this case, the antibody against cytochrome b5 could not inhibit the reaction, while the antibody against NADH-cytochrome b5 reductase did inhibit it, suggesting the direct transfer of electrons from NADH-cytochrome b5 reductase to EDTA-Fe complex."}
{"id": "PMID:24623", "title": "The structure and function of acid proteases. VIII. Purification and characterization of cathepsins D from Japanese monkey lung.", "content": "Two kinds of cathepsin D were found in Japanese monkey lung and were named cathepsins D-I and D-II. Cathepsin D-I was partially purified by ammonium sulfate fractionation and DEAE-cellulose column chromatography. It had properties common to other ordinary cathepsins D in terms of the elution position from a DEAE-cellulose column at pH 8.0, the pH-dependence of activity toward acid-denatured hemoglobin, and the molecular weight of 35,000 as determined by Sephadex G-100 gel filtration. On the other hand, cathepsin D-II was purified about 1,000-fold by a combination of ammonium sulfate fractionation and column chromatographies on DEAE-cellulose and Sephadex G-100. It was a very acidic protein as judged from its elution position from a DEAE-cellulose column at pH 8.0, and the high mobility toward the anode on disc gel electrophoresis at pH 8.6. Its molecular weight was determined to be 35,000 by Sephadex G-100 gel filtration and 39,000 by SDS-polyacrylamide gel electrophoresis. It was optimally active at pH 2.8 against acid-denatured hemoglobin as a substrate, showing 80% of the optimal activity at pH 1.0, and almost no activity above pH 4.0. This pH-profile of activity was similar to that of monkey pepsin C (gastricsin). It did not hydrolyze N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine, a synthetic substrate for pepsin, but was inhibited by a series of pepsin inhibitors such as pepstatin, 1,2-epoxy-3-(p-nitrophenoxy)propane, p-bromophenacyl bromide, and diazoacetyl-DL-norleucine methyl ester, although the diazo reagent was a rather weak inhibitor of the enzyme. The amino acid composition of cathepsin D-II was found to be fairly different from those of other cathepsins D. However, it showed a striking resemblance to that of Japanese monkey pepsinogen C, suggesting some evolutionary relationship between them.", "contents": "The structure and function of acid proteases. VIII. Purification and characterization of cathepsins D from Japanese monkey lung. Two kinds of cathepsin D were found in Japanese monkey lung and were named cathepsins D-I and D-II. Cathepsin D-I was partially purified by ammonium sulfate fractionation and DEAE-cellulose column chromatography. It had properties common to other ordinary cathepsins D in terms of the elution position from a DEAE-cellulose column at pH 8.0, the pH-dependence of activity toward acid-denatured hemoglobin, and the molecular weight of 35,000 as determined by Sephadex G-100 gel filtration. On the other hand, cathepsin D-II was purified about 1,000-fold by a combination of ammonium sulfate fractionation and column chromatographies on DEAE-cellulose and Sephadex G-100. It was a very acidic protein as judged from its elution position from a DEAE-cellulose column at pH 8.0, and the high mobility toward the anode on disc gel electrophoresis at pH 8.6. Its molecular weight was determined to be 35,000 by Sephadex G-100 gel filtration and 39,000 by SDS-polyacrylamide gel electrophoresis. It was optimally active at pH 2.8 against acid-denatured hemoglobin as a substrate, showing 80% of the optimal activity at pH 1.0, and almost no activity above pH 4.0. This pH-profile of activity was similar to that of monkey pepsin C (gastricsin). It did not hydrolyze N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine, a synthetic substrate for pepsin, but was inhibited by a series of pepsin inhibitors such as pepstatin, 1,2-epoxy-3-(p-nitrophenoxy)propane, p-bromophenacyl bromide, and diazoacetyl-DL-norleucine methyl ester, although the diazo reagent was a rather weak inhibitor of the enzyme. The amino acid composition of cathepsin D-II was found to be fairly different from those of other cathepsins D. However, it showed a striking resemblance to that of Japanese monkey pepsinogen C, suggesting some evolutionary relationship between them."}
{"id": "PMID:24626", "title": "Successive purification of several enzymes having affinities for phosphoric groups of substrates by affinity chromatography on P-cellulose.", "content": "Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase and pyruvate kinase of Candida utilis and baker's yeast, when in anionic form, were adsorbed on a cation exchanger, P-cellulose, due to affinities similar to those for the phosphoric groups of their respective substrates; thus, glucose-6-phosphate dehydrogenase was readily eluted by either NADP+ or NADPH, glutathione reductase by NADPH, 6-phosphogluconate dehydrogenase by 6-phosphogluconate, and pyruvate kinase by either ATP or ADP. This type of chromatography may be called \"affinity-adsorption-elution chromatography\"; the main principle is different from that of so-called affinity-elution chromatography. Based on these findings, a large-scale procedure suitable for successive purification of several enzymes having affinities for the phosphoric groups of their substrates was devised. As an example, glucose-6-phosphate dehydrogenase was highly purified from baker's yeast and crystallized.", "contents": "Successive purification of several enzymes having affinities for phosphoric groups of substrates by affinity chromatography on P-cellulose. Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase and pyruvate kinase of Candida utilis and baker's yeast, when in anionic form, were adsorbed on a cation exchanger, P-cellulose, due to affinities similar to those for the phosphoric groups of their respective substrates; thus, glucose-6-phosphate dehydrogenase was readily eluted by either NADP+ or NADPH, glutathione reductase by NADPH, 6-phosphogluconate dehydrogenase by 6-phosphogluconate, and pyruvate kinase by either ATP or ADP. This type of chromatography may be called \"affinity-adsorption-elution chromatography\"; the main principle is different from that of so-called affinity-elution chromatography. Based on these findings, a large-scale procedure suitable for successive purification of several enzymes having affinities for the phosphoric groups of their substrates was devised. As an example, glucose-6-phosphate dehydrogenase was highly purified from baker's yeast and crystallized."}
{"id": "PMID:24627", "title": "Isolation and some properties of a deoxyribonuclease from Turbo cornutus.", "content": "1. Four DNases were found in the dried liver extract of a top shell, Turbo cornutus. The major one was purified 120-fold by phosphocellulose column chromatography, sulfoethylcellulose column chromatography and gel-filtration on Sephadex G-150. The yield was 2.7%. 2. The enzyme activity was not affected by Mg2+ (10(-3)--10(-2)M), EDTA (10(-3)--10(-2)M), or NaCl (10(-1)M). It showed a pH optimum of 4.7--4.8. Ionic strength was found to be critical for the maximal activity. The isoelectric point was 8.5--9.0. On heating at 50 degrees C C for 5 min the enzymic activity fell to half the initial value. 3. The enzyme preparation degraded native as well as heat-denatured DNA, but not RNA. It degraded heat-denatured DNA endonucleolytically to give oligonucleotides with 3'-phosphates. 4. The 3'-phosphate and 5'-hydroxy termini of oligonucleotides were investigated. At both the 3'- and 5'-terminal positions, purine nucleotides were predominant.", "contents": "Isolation and some properties of a deoxyribonuclease from Turbo cornutus. 1. Four DNases were found in the dried liver extract of a top shell, Turbo cornutus. The major one was purified 120-fold by phosphocellulose column chromatography, sulfoethylcellulose column chromatography and gel-filtration on Sephadex G-150. The yield was 2.7%. 2. The enzyme activity was not affected by Mg2+ (10(-3)--10(-2)M), EDTA (10(-3)--10(-2)M), or NaCl (10(-1)M). It showed a pH optimum of 4.7--4.8. Ionic strength was found to be critical for the maximal activity. The isoelectric point was 8.5--9.0. On heating at 50 degrees C C for 5 min the enzymic activity fell to half the initial value. 3. The enzyme preparation degraded native as well as heat-denatured DNA, but not RNA. It degraded heat-denatured DNA endonucleolytically to give oligonucleotides with 3'-phosphates. 4. The 3'-phosphate and 5'-hydroxy termini of oligonucleotides were investigated. At both the 3'- and 5'-terminal positions, purine nucleotides were predominant."}
{"id": "PMID:24628", "title": "Aliesterase activity in normal and postheparin human blood sera.", "content": "An enzyme with characteristics typical of aliesterase has been found in human blood serum using a gas solid chromatographic assay technique. This conflicts with the findings of several authors that aliesterase is absent in the human blood. Another aliesterase is released into the blood stream after intravenous administration of heparin. Partial purification of the aliesterase in normal (preheparin) and postheparin sera was effected by column chromatography using CM- and DEAE-Sephadex. The preheparin aliesterase and postheparin aliesterase have different pH optima of 7.0 and 8.5 respectively. The preheparin aliesterase activity was very sensitive to sodium fluoride and insensitive to a negatively charged detergent, sodium lauryl sulfate, unlike the postheparin esterase which was highly sensitive to sodium lauryl sulfate and comparatively less sensitive to sodium fluoride.", "contents": "Aliesterase activity in normal and postheparin human blood sera. An enzyme with characteristics typical of aliesterase has been found in human blood serum using a gas solid chromatographic assay technique. This conflicts with the findings of several authors that aliesterase is absent in the human blood. Another aliesterase is released into the blood stream after intravenous administration of heparin. Partial purification of the aliesterase in normal (preheparin) and postheparin sera was effected by column chromatography using CM- and DEAE-Sephadex. The preheparin aliesterase and postheparin aliesterase have different pH optima of 7.0 and 8.5 respectively. The preheparin aliesterase activity was very sensitive to sodium fluoride and insensitive to a negatively charged detergent, sodium lauryl sulfate, unlike the postheparin esterase which was highly sensitive to sodium lauryl sulfate and comparatively less sensitive to sodium fluoride."}
{"id": "PMID:24629", "title": "Phosphoglycolate phosphatase. Effect of cation and pH on activity.", "content": "P-glycolate phosphatase requires divalent cations for activity. Activity-pH curves identified 2 active site residues with pK values at pH 5.7 and pH 9.1 in the presence of magnesium and at pH 5.7 and pH 7.5 in the presence of manganese or cobalt. Saturation velocity kinetics enabled the identification of two distinct divalent cation binding sites. The first, nonspecific site has a K0.5 of 2 to 7 x 10(-5) M, depending on the cation and the pH. The second site, which is specific for magnesium, binds this cation in a negatively cooperative fashion. The affinity at pH 8.1 varies approximately 100-fold from the first magnesium bound to the fourth. The negative cooperativity is greatest at high pH. Because the pH range of activity is very broad, both the phosphate monoanion and dianion of P-glycolate must be bound as the substrate. The concentration of these two species at the apparent Km is independent of magnesium concentration. The P-glycolate.magnesium complex is kinetically inactive.", "contents": "Phosphoglycolate phosphatase. Effect of cation and pH on activity. P-glycolate phosphatase requires divalent cations for activity. Activity-pH curves identified 2 active site residues with pK values at pH 5.7 and pH 9.1 in the presence of magnesium and at pH 5.7 and pH 7.5 in the presence of manganese or cobalt. Saturation velocity kinetics enabled the identification of two distinct divalent cation binding sites. The first, nonspecific site has a K0.5 of 2 to 7 x 10(-5) M, depending on the cation and the pH. The second site, which is specific for magnesium, binds this cation in a negatively cooperative fashion. The affinity at pH 8.1 varies approximately 100-fold from the first magnesium bound to the fourth. The negative cooperativity is greatest at high pH. Because the pH range of activity is very broad, both the phosphate monoanion and dianion of P-glycolate must be bound as the substrate. The concentration of these two species at the apparent Km is independent of magnesium concentration. The P-glycolate.magnesium complex is kinetically inactive."}
{"id": "PMID:24630", "title": "gamma-Glutamyl cyclotransferase from rat kidney. Sulfhydryl groups and isolation of a stable form of the enzyme.", "content": "gamma-Glutamyl cyclotransferase, highly purified from rat kidney, contains several readily accessible sulfhydryl groups whose modification appears to be associated with the appearance of multiple enzyme forms as determined by isoelectric focusing and ion exchange chromatography. The enzyme was obtained in a 1000-fold purified and apparently homogeneous form by a procedures involving treatment with dithiothreitol followed by chromatography on thiol-Sepharose. The enzyme was also isolated in a highly active, apparently homogeneous, and stable form after reduction and treatment with iodoacetamide. The amino acid compositions and other properties of the two forms of the enzyme were very similar. Studies on the activity of the enzyme toward a variety of gamma-glutamyl amino acids and di-gamma-glutamyl amino acids showed that the enzyme is much more active toward certain di-gamma-glutamyl amino acids than toward the corresponding gamma-glutamyl amino acids; thus, the preferred substrates have the general structure gamma-Glu-gamma-Glu-NH-R in which the nature of the R moiety has relatively little effect on activity.", "contents": "gamma-Glutamyl cyclotransferase from rat kidney. Sulfhydryl groups and isolation of a stable form of the enzyme. gamma-Glutamyl cyclotransferase, highly purified from rat kidney, contains several readily accessible sulfhydryl groups whose modification appears to be associated with the appearance of multiple enzyme forms as determined by isoelectric focusing and ion exchange chromatography. The enzyme was obtained in a 1000-fold purified and apparently homogeneous form by a procedures involving treatment with dithiothreitol followed by chromatography on thiol-Sepharose. The enzyme was also isolated in a highly active, apparently homogeneous, and stable form after reduction and treatment with iodoacetamide. The amino acid compositions and other properties of the two forms of the enzyme were very similar. Studies on the activity of the enzyme toward a variety of gamma-glutamyl amino acids and di-gamma-glutamyl amino acids showed that the enzyme is much more active toward certain di-gamma-glutamyl amino acids than toward the corresponding gamma-glutamyl amino acids; thus, the preferred substrates have the general structure gamma-Glu-gamma-Glu-NH-R in which the nature of the R moiety has relatively little effect on activity."}
{"id": "PMID:24631", "title": "Sea urchin sperm guanylate cyclase antibody. Cross-reactivity various rat tissue guanylate cyclases.", "content": "After the repeated injection of sea urchin sperm guanylate cyclase into rabbits, antibodies to the enzyme were formed. These antibodies inhibited the particulate or the Triton-dispersed forms of the sperm enzyme by greater than 97%. The sperm adenylate cyclase, cyclic GMP phosphodiesterase, adenosine triphosphatase, guanosine triphosphatase, and 5'-nucleotidase enzymes were not affected by the antiserum. The antiserum inhibited the Triton-dispersed guanylate cyclase from rat heart, liver, lung, spleen, and kidney but did not inhibit the soluble form of the enzyme from any of these tissues. The inhibition of the Triton-dispersed enzyme in these tissues was partial, however, ranging from 30% (liver) to 70% (heart). These results provide evidence that adenylate cyclase is antigenically different from guanylate cyclase, and that the soluble form of guanylate cyclase is antigenically different from a particulate form of the enzyme in various rat tissues.", "contents": "Sea urchin sperm guanylate cyclase antibody. Cross-reactivity various rat tissue guanylate cyclases. After the repeated injection of sea urchin sperm guanylate cyclase into rabbits, antibodies to the enzyme were formed. These antibodies inhibited the particulate or the Triton-dispersed forms of the sperm enzyme by greater than 97%. The sperm adenylate cyclase, cyclic GMP phosphodiesterase, adenosine triphosphatase, guanosine triphosphatase, and 5'-nucleotidase enzymes were not affected by the antiserum. The antiserum inhibited the Triton-dispersed guanylate cyclase from rat heart, liver, lung, spleen, and kidney but did not inhibit the soluble form of the enzyme from any of these tissues. The inhibition of the Triton-dispersed enzyme in these tissues was partial, however, ranging from 30% (liver) to 70% (heart). These results provide evidence that adenylate cyclase is antigenically different from guanylate cyclase, and that the soluble form of guanylate cyclase is antigenically different from a particulate form of the enzyme in various rat tissues."}
{"id": "PMID:24632", "title": "Purification and properties of mosquito DNA polymerase.", "content": "For the first time, DNA polymerase in a postembryonic insect has been purified and characterized. This enzyme from mosquito larvae was purified 1700-fold and was free of deoxyribonuclease and protease activities, which hindered previous investigations of insect polymerases. The enzyme had a molecular weight of 132,000 by gen filtration and  aggregated to higher molecular weights when concentrated. With an activated DNA template, the pH optimum was 7.2 in phosphate buffer, and the Mg2+ concentration optimum was 5 to 10 mM. Polymerase activity was inhibited by the antisulfhydryl reagents, N-ethylmaleimide and p-mercuribenzoate, and by KCl. These properties indicate that the mosquito enzyme resembles mammalian alpha-polymerase but differs in its lack of inhibition to low ethanol concentrations. There was no evidence of a beta-polymerase form in the mosquito.", "contents": "Purification and properties of mosquito DNA polymerase. For the first time, DNA polymerase in a postembryonic insect has been purified and characterized. This enzyme from mosquito larvae was purified 1700-fold and was free of deoxyribonuclease and protease activities, which hindered previous investigations of insect polymerases. The enzyme had a molecular weight of 132,000 by gen filtration and  aggregated to higher molecular weights when concentrated. With an activated DNA template, the pH optimum was 7.2 in phosphate buffer, and the Mg2+ concentration optimum was 5 to 10 mM. Polymerase activity was inhibited by the antisulfhydryl reagents, N-ethylmaleimide and p-mercuribenzoate, and by KCl. These properties indicate that the mosquito enzyme resembles mammalian alpha-polymerase but differs in its lack of inhibition to low ethanol concentrations. There was no evidence of a beta-polymerase form in the mosquito."}
{"id": "PMID:24635", "title": "Purification and properties of an NADPH-dependent 21-oxo-20-hydroxysteroid reductase (17beta-aldol reductase) from sheep liver. Isolation of the 20beta-glycol product.", "content": "This investigation was undertaken to test the hypothesis that steroidal 20-hydroxy-21-aldehydes are intermediates in an alternative pathway of corticosteroid metabolism leading to steroidal 20,21-diols. A NADPH-dependent 21-oxo-20-hydroxysteroid reductase which catalyzed the reduction of 11beta,17,20beta-trihydroxy-3-keto-4-pregnen-21-al (isocortisol) to 11beta,17,20beta,21-tetrahydroxy-4-pregnen-3-one (Reichstein's compound E) was prepared from sheep liver. Other steroidal 17-aldols were also good substrates. Some steroidal 17-oxoaldehydes, D-, and L-glyceraldehyde were reduced, but less effectively than the steroidal aldols. Steroidal ketols and 21-oic acids were not substrates. The enzyme contains--SH groups, has a pH optimum of 6.9 to 7.5 and a molecular weight of about 28,000. Reversibility of the enzymic reaction could not be demonstrated. The reduction product obtained from isocortisol was isolated and characterized. Other 17-glycols were derived from their respective steroid aldols. Reductase activity was also present in hamster and rat liver. From a comparison of 21-oxo-20-hydroxysteroid reductase and 21-hydroxysteroid dehydrogenase with respect to pH optima, substrate specificity, stability to heat, and kinetic constants, we conclude that the two enzymes are distinct.", "contents": "Purification and properties of an NADPH-dependent 21-oxo-20-hydroxysteroid reductase (17beta-aldol reductase) from sheep liver. Isolation of the 20beta-glycol product. This investigation was undertaken to test the hypothesis that steroidal 20-hydroxy-21-aldehydes are intermediates in an alternative pathway of corticosteroid metabolism leading to steroidal 20,21-diols. A NADPH-dependent 21-oxo-20-hydroxysteroid reductase which catalyzed the reduction of 11beta,17,20beta-trihydroxy-3-keto-4-pregnen-21-al (isocortisol) to 11beta,17,20beta,21-tetrahydroxy-4-pregnen-3-one (Reichstein's compound E) was prepared from sheep liver. Other steroidal 17-aldols were also good substrates. Some steroidal 17-oxoaldehydes, D-, and L-glyceraldehyde were reduced, but less effectively than the steroidal aldols. Steroidal ketols and 21-oic acids were not substrates. The enzyme contains--SH groups, has a pH optimum of 6.9 to 7.5 and a molecular weight of about 28,000. Reversibility of the enzymic reaction could not be demonstrated. The reduction product obtained from isocortisol was isolated and characterized. Other 17-glycols were derived from their respective steroid aldols. Reductase activity was also present in hamster and rat liver. From a comparison of 21-oxo-20-hydroxysteroid reductase and 21-hydroxysteroid dehydrogenase with respect to pH optima, substrate specificity, stability to heat, and kinetic constants, we conclude that the two enzymes are distinct."}
{"id": "PMID:24637", "title": "Differential inhibition of glutamine and gamma-glutamylcysteine synthetases by alpha-alkyl analogs of methionine sulfoximine that induce convulsions.", "content": "The alpha-methyl and alpha-ethyl analogs of methionine sulfoximine, like methionine sulfoximine, induce convulsions in mice and inhibit glutamine synthetase irreversibly; alpha-ethylmethionine sulfoximine is approximately 50% as inhibitory as methionine sulfoximine and alpha-methylmethionine sulfoximine. However, whereas alpha-methylmethionine sulfoximine and methionine sulfoximine inhibit gamma-glutamylcysteine synthetase markedly, alpha-ethylmethionine sulfoximine does not, nor does administration of the alpha-ethyl analog produce the decrease in tissue glutathione levels found after giving methionine sulfoximine or its alpha-methyl analog. The findings strongly indicate that methionine sulfoximine-induced convulsions are closely associated with inhibition of glutamine synthetase rather than with inhibition of gamma-glutamylcysteine synthetase. The alpha-alkyl methionine sulfoximine analogs cannot be catabolized via the corresponding alpha-keto or alpha-imino acids, and, like other alpha-substituted amino acids, are probably not metabolized to a significant extent in vivo; this suggests that the amino acid sulfoximine molecules themselves, rather than their metabolites, are directly involved in the induction of convulsions. Possible explanations for the reported lack of correlation between the occurrence of convulsions and the levels of glutamine synthetase activity (and its substrates and product) are considered. The findings suggest that studies on the mechanism of induction of convulsions may be extended significantly and refined in biochemical terms by the use of other structurally modified convulsant molecules.", "contents": "Differential inhibition of glutamine and gamma-glutamylcysteine synthetases by alpha-alkyl analogs of methionine sulfoximine that induce convulsions. The alpha-methyl and alpha-ethyl analogs of methionine sulfoximine, like methionine sulfoximine, induce convulsions in mice and inhibit glutamine synthetase irreversibly; alpha-ethylmethionine sulfoximine is approximately 50% as inhibitory as methionine sulfoximine and alpha-methylmethionine sulfoximine. However, whereas alpha-methylmethionine sulfoximine and methionine sulfoximine inhibit gamma-glutamylcysteine synthetase markedly, alpha-ethylmethionine sulfoximine does not, nor does administration of the alpha-ethyl analog produce the decrease in tissue glutathione levels found after giving methionine sulfoximine or its alpha-methyl analog. The findings strongly indicate that methionine sulfoximine-induced convulsions are closely associated with inhibition of glutamine synthetase rather than with inhibition of gamma-glutamylcysteine synthetase. The alpha-alkyl methionine sulfoximine analogs cannot be catabolized via the corresponding alpha-keto or alpha-imino acids, and, like other alpha-substituted amino acids, are probably not metabolized to a significant extent in vivo; this suggests that the amino acid sulfoximine molecules themselves, rather than their metabolites, are directly involved in the induction of convulsions. Possible explanations for the reported lack of correlation between the occurrence of convulsions and the levels of glutamine synthetase activity (and its substrates and product) are considered. The findings suggest that studies on the mechanism of induction of convulsions may be extended significantly and refined in biochemical terms by the use of other structurally modified convulsant molecules."}
{"id": "PMID:24638", "title": "Stabilization of the relaxed state of aspartate transcarbamoylase by modification with a bifunctional reagent.", "content": "Native aspartate transcarbamoylase from Escherichia coli was modified with the bifunctional reagent tartaryl diazide in the presence of the substrate carbamoyl phosphate and the substrate analog succinate. The product had the same sedimentation coefficient as the native enzyme but showed a marked increase in affinity for the substrate aspartate with a hyperbolic saturation curve. The Michaelis constant for aspartate (7.4 mM) is similar to that estimated for the relaxed state of the enzyme. The high substrate affinity was not produced if modification was conducted in the absence of substrate analogs or with a monofunctional reagent. The modified enzyme was also desensitized towards the allosteric effectors ATP and CTP. It appears to represent a stabilized relaxed state whose conversion to the taut state is presumably prevented by cross-linking.", "contents": "Stabilization of the relaxed state of aspartate transcarbamoylase by modification with a bifunctional reagent. Native aspartate transcarbamoylase from Escherichia coli was modified with the bifunctional reagent tartaryl diazide in the presence of the substrate carbamoyl phosphate and the substrate analog succinate. The product had the same sedimentation coefficient as the native enzyme but showed a marked increase in affinity for the substrate aspartate with a hyperbolic saturation curve. The Michaelis constant for aspartate (7.4 mM) is similar to that estimated for the relaxed state of the enzyme. The high substrate affinity was not produced if modification was conducted in the absence of substrate analogs or with a monofunctional reagent. The modified enzyme was also desensitized towards the allosteric effectors ATP and CTP. It appears to represent a stabilized relaxed state whose conversion to the taut state is presumably prevented by cross-linking."}
{"id": "PMID:24639", "title": "Inactivation of human gamma-glutamylcysteine synthetase by cystamine. Demonstration and quantification of enzyme-ligand complexes.", "content": "Human erythrocyte gamma-glutamylcysteine synthetase is inactivated by the disulfide cystamine (2,2'-dithiobis-(ethylamine)) at pH 8.2 with a rate constant of 1020 min-1 mM-1. Magnesium ion and various combinations of substrates and products confer differing degrees of protection against cystamine inactivation, thus allowing the detection and quantification of certain enzyme-ligand interactions. By measuring inactivation rates as a function of ligand concentrations in incomplete reaction mixtures, we have obtained evidence for the following complexes: enzyme . Mg2+; enzyme . Mg2+ . MgATP2-; enzyme . Mg2+ . L-glutamate; enzyme . Mg2+ . MgATP2- . L-glutamate; enzyme . Mg2+ . L-gamma-glutamyl-L-alpha-aminobutyrate. The data also imply the existence of enzyme . (Mg2+)2 . MgATP2- . L-glutamate and several enzyme forms resulting from the weak binding to L-alpha-aminobutyrate. The methods used permit the calculation of cystamine inactivation rates for most of these enzyme forms and also give values for the equilibrium constants describing their formation.", "contents": "Inactivation of human gamma-glutamylcysteine synthetase by cystamine. Demonstration and quantification of enzyme-ligand complexes. Human erythrocyte gamma-glutamylcysteine synthetase is inactivated by the disulfide cystamine (2,2'-dithiobis-(ethylamine)) at pH 8.2 with a rate constant of 1020 min-1 mM-1. Magnesium ion and various combinations of substrates and products confer differing degrees of protection against cystamine inactivation, thus allowing the detection and quantification of certain enzyme-ligand interactions. By measuring inactivation rates as a function of ligand concentrations in incomplete reaction mixtures, we have obtained evidence for the following complexes: enzyme . Mg2+; enzyme . Mg2+ . MgATP2-; enzyme . Mg2+ . L-glutamate; enzyme . Mg2+ . MgATP2- . L-glutamate; enzyme . Mg2+ . L-gamma-glutamyl-L-alpha-aminobutyrate. The data also imply the existence of enzyme . (Mg2+)2 . MgATP2- . L-glutamate and several enzyme forms resulting from the weak binding to L-alpha-aminobutyrate. The methods used permit the calculation of cystamine inactivation rates for most of these enzyme forms and also give values for the equilibrium constants describing their formation."}
{"id": "PMID:24642", "title": "Characterization of microtubule protein oligomers by analytical ultracentrifugation.", "content": "Samples of microtubule protein prepared by repeated cycles of assembly-disassembly were examined at low temperatures by sedimentation velocity ultracentrifugation. Sedimenting boundaries corresponding to the 6 S tubulin subunit as well as to two oligomeric species with s020,w values of 18.6 S and 30.6 S were observed. The 30 S to 6 S mass ratio varied with total protein concentration, suggesting that a concentration-dependent equilibrium exists between 6 S and oligomeric species of tubulin. A study of the effects of pH on the mass distribution among the species demonstrated that the 6 S species was favored at low pH values (5.8 to 6.5), the 30 S oligomer was favored at moderate pH values (6.5 to 7.4), and the 18 S oligomer was formed in increasing proportions at higher pH values (7.4 to 8.2). Incubation of purified microtubule protein solutions with increasing concentrations of NaCl initially favored conversion of the 30 S oligomer to the 18 S species with further increases in salt concentration resulting in the dissolution of both the 30 S and 18 S oligomers. The depolymerizing effects of high salt concentrations were substantially reversible, providing further evidence for 6 S-oligomer equilibria. The manipulation of the solution variables of pH and ionic strength in a systematic fashion led to the construction of a \"phase diagram\" for the microtubule protein species which provided a relatively complete description of the mass distribution among the 6 S, 18 S, and 30 S species over a range of physiological and near-physiological solution conditions.", "contents": "Characterization of microtubule protein oligomers by analytical ultracentrifugation. Samples of microtubule protein prepared by repeated cycles of assembly-disassembly were examined at low temperatures by sedimentation velocity ultracentrifugation. Sedimenting boundaries corresponding to the 6 S tubulin subunit as well as to two oligomeric species with s020,w values of 18.6 S and 30.6 S were observed. The 30 S to 6 S mass ratio varied with total protein concentration, suggesting that a concentration-dependent equilibrium exists between 6 S and oligomeric species of tubulin. A study of the effects of pH on the mass distribution among the species demonstrated that the 6 S species was favored at low pH values (5.8 to 6.5), the 30 S oligomer was favored at moderate pH values (6.5 to 7.4), and the 18 S oligomer was formed in increasing proportions at higher pH values (7.4 to 8.2). Incubation of purified microtubule protein solutions with increasing concentrations of NaCl initially favored conversion of the 30 S oligomer to the 18 S species with further increases in salt concentration resulting in the dissolution of both the 30 S and 18 S oligomers. The depolymerizing effects of high salt concentrations were substantially reversible, providing further evidence for 6 S-oligomer equilibria. The manipulation of the solution variables of pH and ionic strength in a systematic fashion led to the construction of a \"phase diagram\" for the microtubule protein species which provided a relatively complete description of the mass distribution among the 6 S, 18 S, and 30 S species over a range of physiological and near-physiological solution conditions."}
{"id": "PMID:24643", "title": "Relation of protein synthesis and transglutaminase activity to formation of the cross-linked envelope during terminal differentiation of the cultured human epidermal keratinocyte.", "content": "When serially cultivated human epidermal keratinocytes are placed in suspension culture they stop growing and form, beneath the plasma membrane, an insoluble envelope consisting of protein cross-linked by epsilon- (gamma-glutamyl)lysine. The formation of envelopes in suspended cells is preceded by a sharp decline in the rate of protein synthesis, and most envelopes appear only after the average rate of protein synthesis has fallen to a very low level. If protein synthesis is reduced over 98 percent with cycloheximide or emetine at the time that surface-grown cells are placed in suspension culture, cross-linked envelopes form in most of the cells. This shows that the precursor of the envelope and the cross-linking enzyme are already in the cytoplasm in most cells of growing surface cultures. The process of envelope formation by suspension cultures is actually accelerated by the inhibitors of protein synthesis; an increased number of cells with cross-linked envelopes is observable within 4-6 h after the addition of cycloheximide. The inhibitor also induces a large fraction of the cells of surface cultures to form enveloped within a few days. These findings suggest that arrest of protein synthesis leads to activation of the cross-linking process. Agents known to inhibit transglutaminase-mediated protein cross-linking-putrescine, iodoacetamide, and ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA)- also prevent envelope formation. Though the activity of the cross-linking transglutaminase depends on the presence of cellular Ca++, we have not been able to activate the cross-linking process by high external Ca++ concentration or ionophores.", "contents": "Relation of protein synthesis and transglutaminase activity to formation of the cross-linked envelope during terminal differentiation of the cultured human epidermal keratinocyte. When serially cultivated human epidermal keratinocytes are placed in suspension culture they stop growing and form, beneath the plasma membrane, an insoluble envelope consisting of protein cross-linked by epsilon- (gamma-glutamyl)lysine. The formation of envelopes in suspended cells is preceded by a sharp decline in the rate of protein synthesis, and most envelopes appear only after the average rate of protein synthesis has fallen to a very low level. If protein synthesis is reduced over 98 percent with cycloheximide or emetine at the time that surface-grown cells are placed in suspension culture, cross-linked envelopes form in most of the cells. This shows that the precursor of the envelope and the cross-linking enzyme are already in the cytoplasm in most cells of growing surface cultures. The process of envelope formation by suspension cultures is actually accelerated by the inhibitors of protein synthesis; an increased number of cells with cross-linked envelopes is observable within 4-6 h after the addition of cycloheximide. The inhibitor also induces a large fraction of the cells of surface cultures to form enveloped within a few days. These findings suggest that arrest of protein synthesis leads to activation of the cross-linking process. Agents known to inhibit transglutaminase-mediated protein cross-linking-putrescine, iodoacetamide, and ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA)- also prevent envelope formation. Though the activity of the cross-linking transglutaminase depends on the presence of cellular Ca++, we have not been able to activate the cross-linking process by high external Ca++ concentration or ionophores."}
{"id": "PMID:24644", "title": "Serum standards for the bioassay of aminoglycosides in cerebrospinal fluid.", "content": "Four diluents were compared as reference standards for the assay of gentamicin in cerebrospinal fluid (CSF): human CSF, human serum, distilled water, and 150 mmol NaCl/4.5 mmol CaCl2. Standards prepared in pooled human serum were the best alternative to CSF for the assay of gentamicin and were also useful for the assay of tobramycin, netilmicin, amikacin, and sisomicin. The pH (6.0-9.8) of CSF did not alter the results of the assay.", "contents": "Serum standards for the bioassay of aminoglycosides in cerebrospinal fluid. Four diluents were compared as reference standards for the assay of gentamicin in cerebrospinal fluid (CSF): human CSF, human serum, distilled water, and 150 mmol NaCl/4.5 mmol CaCl2. Standards prepared in pooled human serum were the best alternative to CSF for the assay of gentamicin and were also useful for the assay of tobramycin, netilmicin, amikacin, and sisomicin. The pH (6.0-9.8) of CSF did not alter the results of the assay."}
{"id": "PMID:24645", "title": "The effects of one-day treatment of anxiety with high doses of halazepam.", "content": "The main purposes of this study were to examine the effects of one-day treatment of anxiety and to test whether significant relief of anxiety can be achieved in a short time period by frequency individual adjustment of doses. A double-blind crossover study of halazepam and placebo was carried out with 22 patients, 20 completing the study. Each treatment lasted for one day. Oral medication was administered starting with a dose of 40 mg and the dose adjusted every 2 hours. The total daily dose did not exceed 600 mg. Several rating and self-rating scales were used. All observer rating scales and several self-rating scales discriminated at a significant level. The design appeart to be suitable for the rapid screening for anti-anxiety properties of new drugs.", "contents": "The effects of one-day treatment of anxiety with high doses of halazepam. The main purposes of this study were to examine the effects of one-day treatment of anxiety and to test whether significant relief of anxiety can be achieved in a short time period by frequency individual adjustment of doses. A double-blind crossover study of halazepam and placebo was carried out with 22 patients, 20 completing the study. Each treatment lasted for one day. Oral medication was administered starting with a dose of 40 mg and the dose adjusted every 2 hours. The total daily dose did not exceed 600 mg. Several rating and self-rating scales were used. All observer rating scales and several self-rating scales discriminated at a significant level. The design appeart to be suitable for the rapid screening for anti-anxiety properties of new drugs."}
{"id": "PMID:24646", "title": "A study in the management of anxiety with lorazepam.", "content": "A four-week double-blind comparison between lorazepam and placebo involving 60 patients with anxiety revealed that lorazepam in a mean dose of approximately 3 mg on a b.i.d. regimen is significantly and clinically more effective than placebo for almost all items of the Global, Hamilton, and 35-Item scales at nearly all evaluation periods. Moreover, lorazapem was associated with a 50% greater improvement rate than was placebo. Except for only one patient who was withdrawn from the study because of severe sedation, lorazepam was well tolerated and did not interact adversely with concomitant nonpsychoactive medication.", "contents": "A study in the management of anxiety with lorazepam. A four-week double-blind comparison between lorazepam and placebo involving 60 patients with anxiety revealed that lorazepam in a mean dose of approximately 3 mg on a b.i.d. regimen is significantly and clinically more effective than placebo for almost all items of the Global, Hamilton, and 35-Item scales at nearly all evaluation periods. Moreover, lorazapem was associated with a 50% greater improvement rate than was placebo. Except for only one patient who was withdrawn from the study because of severe sedation, lorazepam was well tolerated and did not interact adversely with concomitant nonpsychoactive medication."}
{"id": "PMID:24647", "title": "Acid base status during treatment of chronic uremia with diafiltration.", "content": "Treatment of chronic uremia by hemodiafiltration requires replacement of the filtrate. Using Ringer's solution alone, there is a depression of pH because of bicarbonate loss. To bring the acid base status back to normal, sodium lactate in increasing concentrations (283 mg% = 32 mM/1, 361 mg% = 40 mM/1; 462 mg% = 51 mM/1; 508 mg% = 57 mM/1) was added to the replacement fluid. The optimal concentration is 450 mg% (=50 mM/1) sodium lactate, provided the following conditions are fulfilled: (a) substitution after the filter; (b) mixing ratio of blood and substitution fluid 1:2. Using 12-15 liters of substitution fluid during a 5 hr treatment, the added lactate amounts to 60 g (=0.54 M). With continuous addition of lactate, the serum concentration of lactate is 3.5 times normal and the concentration of serum pyruvate 4 times normal. An excess lactate concentration, according to Huckabee [1,2], was thus not observed. The sieving coefficients were the following: sodium, potassium, urea, lactate, pyruvate, and phosphate 1; chloride greater then 1; calcium and protein less than 1. Serum osmolality fell, on the average, 9 mOsmol/1 during diafiltration.", "contents": "Acid base status during treatment of chronic uremia with diafiltration. Treatment of chronic uremia by hemodiafiltration requires replacement of the filtrate. Using Ringer's solution alone, there is a depression of pH because of bicarbonate loss. To bring the acid base status back to normal, sodium lactate in increasing concentrations (283 mg% = 32 mM/1, 361 mg% = 40 mM/1; 462 mg% = 51 mM/1; 508 mg% = 57 mM/1) was added to the replacement fluid. The optimal concentration is 450 mg% (=50 mM/1) sodium lactate, provided the following conditions are fulfilled: (a) substitution after the filter; (b) mixing ratio of blood and substitution fluid 1:2. Using 12-15 liters of substitution fluid during a 5 hr treatment, the added lactate amounts to 60 g (=0.54 M). With continuous addition of lactate, the serum concentration of lactate is 3.5 times normal and the concentration of serum pyruvate 4 times normal. An excess lactate concentration, according to Huckabee [1,2], was thus not observed. The sieving coefficients were the following: sodium, potassium, urea, lactate, pyruvate, and phosphate 1; chloride greater then 1; calcium and protein less than 1. Serum osmolality fell, on the average, 9 mOsmol/1 during diafiltration."}
{"id": "PMID:24652", "title": "Kinetics of nitrosation of the herbicide glyphosate.", "content": "The herbicide glyphosate was nitrosated by third-order kinetics to N-nitrosoglyphosate. The nitrosation at 25 degrees C was maximum at the reaction pH of 2.5 and had a pH-dependent rate constant of 2.43 M-2 sec-1. An activation energy of 9.5 kcal mole-1 also suggested that glyphosate is nitrosated very readily. Thiocyanate increased the rate 4.6 fold. The possibility of using these results to predict the formation of N-nitrosoglyphosate under normal agricultural practice is discussed.", "contents": "Kinetics of nitrosation of the herbicide glyphosate. The herbicide glyphosate was nitrosated by third-order kinetics to N-nitrosoglyphosate. The nitrosation at 25 degrees C was maximum at the reaction pH of 2.5 and had a pH-dependent rate constant of 2.43 M-2 sec-1. An activation energy of 9.5 kcal mole-1 also suggested that glyphosate is nitrosated very readily. Thiocyanate increased the rate 4.6 fold. The possibility of using these results to predict the formation of N-nitrosoglyphosate under normal agricultural practice is discussed."}
{"id": "PMID:24664", "title": "Effects of restoring lethally irradiated mice with anti-Thy 1.2-treated bone marrow: graft-vs-host, host-vs-graft, and mitogen reactivity.", "content": "In vitro treatment of A/J mouse bone marrow with anti-Thy 1.2 serum and guinea pig complement (GPC) eliminated its ability to induce graft-vs-host (GVH) mortality in lethally irradiated C57BL/6J x A/F1 (BAF1) mice. The anti-Thy 1.2 and GPC treatment of A/J marrow significantly reduced spleen cell activation by phytohemagglutinin (PHA) but not lipopolysaccharide (LPS) stimulation in A/J mice assayed 6 weeks after lethal irradiation and reconstitution with the treated marrow. However, the anti-Thy 1.2 treatment of A/J bone marrow did not impair the ability of the lethally irradiated, reconstituted, syngeneic mice to reject C57BL/6J skin grafts. We conclude that lymphocytes in bone marrow which are susceptible to inactivation by anti-Thy 1.2 mediate allograft reactions and/or that radioresistant cells which persist in the recipient initiate rejection of allogeneic skin grafts.", "contents": "Effects of restoring lethally irradiated mice with anti-Thy 1.2-treated bone marrow: graft-vs-host, host-vs-graft, and mitogen reactivity. In vitro treatment of A/J mouse bone marrow with anti-Thy 1.2 serum and guinea pig complement (GPC) eliminated its ability to induce graft-vs-host (GVH) mortality in lethally irradiated C57BL/6J x A/F1 (BAF1) mice. The anti-Thy 1.2 and GPC treatment of A/J marrow significantly reduced spleen cell activation by phytohemagglutinin (PHA) but not lipopolysaccharide (LPS) stimulation in A/J mice assayed 6 weeks after lethal irradiation and reconstitution with the treated marrow. However, the anti-Thy 1.2 treatment of A/J bone marrow did not impair the ability of the lethally irradiated, reconstituted, syngeneic mice to reject C57BL/6J skin grafts. We conclude that lymphocytes in bone marrow which are susceptible to inactivation by anti-Thy 1.2 mediate allograft reactions and/or that radioresistant cells which persist in the recipient initiate rejection of allogeneic skin grafts."}
{"id": "PMID:24665", "title": "Generation of low-dose paralysis in the absence of the ability to secrete antibody.", "content": "(CBA/N female x BALB/c male)F1 male mice carry an X-linked defect, originating from CBA/N mice, which renders them unable to generate an antibody response to SSS-III. Histocompatible (BALB/c female x CBA/N male) reciprocal F1 male hybrids do not carry the X-linked defect and therefore generate a readily detectable PFC response to SSS-III, which can be adoptively transferred into nonresponding reciprocal F1 male mice. In the present work, we show that this adoptive response could be inhibited in recipient (CBA/N female x BALB/c male)F1 male nonresponding mice in which low dose paralysis had been induced. Evidence is presented which indicates that such suppression is of host rather than donor cell origin. The capacity to develop low-dose paralysis, a phenomenon that is antigen specific and has been attributed to the action of suppressor T cells, indicates that nonresponding (CBA/N female x BALB/c male) F1 males (and presumably the CBA/N progenitor strain) have the ability to recognize this antigen. Furthermore, since these animals fail to make a serum antibody response to SSS-III, the signal that activates suppressor T cells cannot be circulating antibody or antigen-antibody complexes. These findings are most consistent with the view that low-dose paralysis of the response to SSS-III is not dependent on antibody-mediated feedback inhibition; rather, it is an active process mediated by suppressor T cells.", "contents": "Generation of low-dose paralysis in the absence of the ability to secrete antibody. (CBA/N female x BALB/c male)F1 male mice carry an X-linked defect, originating from CBA/N mice, which renders them unable to generate an antibody response to SSS-III. Histocompatible (BALB/c female x CBA/N male) reciprocal F1 male hybrids do not carry the X-linked defect and therefore generate a readily detectable PFC response to SSS-III, which can be adoptively transferred into nonresponding reciprocal F1 male mice. In the present work, we show that this adoptive response could be inhibited in recipient (CBA/N female x BALB/c male)F1 male nonresponding mice in which low dose paralysis had been induced. Evidence is presented which indicates that such suppression is of host rather than donor cell origin. The capacity to develop low-dose paralysis, a phenomenon that is antigen specific and has been attributed to the action of suppressor T cells, indicates that nonresponding (CBA/N female x BALB/c male) F1 males (and presumably the CBA/N progenitor strain) have the ability to recognize this antigen. Furthermore, since these animals fail to make a serum antibody response to SSS-III, the signal that activates suppressor T cells cannot be circulating antibody or antigen-antibody complexes. These findings are most consistent with the view that low-dose paralysis of the response to SSS-III is not dependent on antibody-mediated feedback inhibition; rather, it is an active process mediated by suppressor T cells."}
{"id": "PMID:24666", "title": "A simplified solid-phase radioimmunoassay for carcinoembryonic antigen.", "content": "A simple and rapid solid-phase radioimmunoassay for the measurement of carcinoembryonic antigen (CEA) levels in sera or plasma is described. The procedure involves perchloric acid (PCA) extraction of the samples, followed by a rapid neutralization of excess acid with alkaline buffer solution. The PCA extracts are assayed uing antibody-coated plastic tubes and radio-labeled anti-CEA antibody as a marker. The assay may be completed in one day. The solid-phase direct-binding assay demonstrated a sensitivity of 0.5 ng CEA/ml plasmin and a marked tolerance to variations in pH and ionic strength of the system. A fair correlation between the CEA levels determined by the solid-phase radioimmunoassay and zirconium phosphate gel method was observed.", "contents": "A simplified solid-phase radioimmunoassay for carcinoembryonic antigen. A simple and rapid solid-phase radioimmunoassay for the measurement of carcinoembryonic antigen (CEA) levels in sera or plasma is described. The procedure involves perchloric acid (PCA) extraction of the samples, followed by a rapid neutralization of excess acid with alkaline buffer solution. The PCA extracts are assayed uing antibody-coated plastic tubes and radio-labeled anti-CEA antibody as a marker. The assay may be completed in one day. The solid-phase direct-binding assay demonstrated a sensitivity of 0.5 ng CEA/ml plasmin and a marked tolerance to variations in pH and ionic strength of the system. A fair correlation between the CEA levels determined by the solid-phase radioimmunoassay and zirconium phosphate gel method was observed."}
{"id": "PMID:24668", "title": "Factors influencing the therapy of experimental Proteus mirabilis meningitis in rabbits.", "content": "The therapy of Proteus mirabilis meningitis with gentamicin alone and in combination with chloramphenicol was studied in a rabbit model. Antibiotics were administered for 8 hr. Samples of serum and cerebrospinal fluid (CSF) obtained simultaneously were assayed at 2-hr intervals for antibiotic concentration and counts of bacteria in CSF. The percentage of penetration ([concentration in CSF divided by concentration in serum] x 100%) of gentamicin ranged from 14% to 23%, but very large dosages were required to kill bacteria in the CSF. Although the minimal bactericidal concentration (MBC) of gentamicin was 1 microgram/ml, killing in vivo occurred only when concentrations in CSF were 10--30 times the MBC. The high concentration required for bactericidal activity in vivo may be explained by the reduced pH of infected CSF (mean pH, 6.98; range, 6.69--7.18). The bactericidal action of gentamicin was abolished by the simultaneous administration of chloramphenicol. Titers of bacteria in CSF were reduced 2.60 log10 (mean) with gentamicin therapy vs. 0.92 log10 (mean) with combination (P less than 0.01).", "contents": "Factors influencing the therapy of experimental Proteus mirabilis meningitis in rabbits. The therapy of Proteus mirabilis meningitis with gentamicin alone and in combination with chloramphenicol was studied in a rabbit model. Antibiotics were administered for 8 hr. Samples of serum and cerebrospinal fluid (CSF) obtained simultaneously were assayed at 2-hr intervals for antibiotic concentration and counts of bacteria in CSF. The percentage of penetration ([concentration in CSF divided by concentration in serum] x 100%) of gentamicin ranged from 14% to 23%, but very large dosages were required to kill bacteria in the CSF. Although the minimal bactericidal concentration (MBC) of gentamicin was 1 microgram/ml, killing in vivo occurred only when concentrations in CSF were 10--30 times the MBC. The high concentration required for bactericidal activity in vivo may be explained by the reduced pH of infected CSF (mean pH, 6.98; range, 6.69--7.18). The bactericidal action of gentamicin was abolished by the simultaneous administration of chloramphenicol. Titers of bacteria in CSF were reduced 2.60 log10 (mean) with gentamicin therapy vs. 0.92 log10 (mean) with combination (P less than 0.01)."}
{"id": "PMID:24669", "title": "Changing ecology of acute bacterial empyema: occurrence and mortality at Boston City Hospital during 12 selected years from 1935 to 1972.", "content": "The occurrence, etiology, and demography of acute bacterial empyema are presented to reflect the widespread use of sulfonamides, penicillin, and other active antibiotics. In community-acquired (C-A) cases Streptococcus pneumoniae, hemolytic streptococci, and Staphylococcus aureus were the most frequent single organisms identified in initial positive cultures of pleural fluid during 1935. S. pneumoniae declined steadily until 1953 but continued to occur frequently in C-A cases. Hemolytic streptococci became infrequent. S. aureus increased and became the most frequent organism in 1955 and declined to original levels after 1965 while gram-negative rods increased. S. aureus, aerobic gram-negative rods, and enterococci were most frequent in originally mixed infections, hospital-acquired cases, and superinfections. Anaerobes with or without aerobes were mostly seen in C-A cases and did not vary in incidence. Mortality increased with age. Overall mortality was greater during the 10 antibiotic years, associated with a marked decrease in the proportion of patients younger than 50 years and increase in those over 60 years old, and was greater in patients with serious underlying diseases subjected to more complicated surgical procedures.", "contents": "Changing ecology of acute bacterial empyema: occurrence and mortality at Boston City Hospital during 12 selected years from 1935 to 1972. The occurrence, etiology, and demography of acute bacterial empyema are presented to reflect the widespread use of sulfonamides, penicillin, and other active antibiotics. In community-acquired (C-A) cases Streptococcus pneumoniae, hemolytic streptococci, and Staphylococcus aureus were the most frequent single organisms identified in initial positive cultures of pleural fluid during 1935. S. pneumoniae declined steadily until 1953 but continued to occur frequently in C-A cases. Hemolytic streptococci became infrequent. S. aureus increased and became the most frequent organism in 1955 and declined to original levels after 1965 while gram-negative rods increased. S. aureus, aerobic gram-negative rods, and enterococci were most frequent in originally mixed infections, hospital-acquired cases, and superinfections. Anaerobes with or without aerobes were mostly seen in C-A cases and did not vary in incidence. Mortality increased with age. Overall mortality was greater during the 10 antibiotic years, associated with a marked decrease in the proportion of patients younger than 50 years and increase in those over 60 years old, and was greater in patients with serious underlying diseases subjected to more complicated surgical procedures."}
{"id": "PMID:24670", "title": "Isolation of the etiologic agent of Korean Hemorrhagic fever.", "content": "Lung tissues from 73 rodents (Apodemus agrarius coreae) gave specific immunofluorescent reactions when they reacted with sera from patients convalescing from Korean hemorrhagic fever. Similar staaining was observed in the lungs of A. agrarius inoculated with acute-phase sera obtained from two patients with this disease. The unidentified agent was successfully propagated in adult A. agrarius through eight passages representing a cumulative dilution of greater than 10(-17). Experimentally inoculated rodents developed specific fluorescent antigen in the lung, kidney, liver, parotid glands, and bladder. Organs, especially lungs, were positive beginning 10 days and continuing through 69 days after inoculation. The agent could not be cultivated in several types of cell cultures nor in laboratory animals. No fluorescence was observed when infected A. agrarius lung tissues were reacted with antisera to Marburg virus, Ebola virus, and serval arenaviruses. Diagnostic increases in immunofluorescent antibodies occurred in 113 of 116 severe and 11 of 34 milder cases of clinically suspected Korean hemorrhagic fever. Antibodies were present during the first week of symptoms, reached a peak at the end of the second week, and persisted for up to 14 years. Convalescent-phase sera from four persons suffering a similar disease in the Soviet Union were also positive for antibodies.", "contents": "Isolation of the etiologic agent of Korean Hemorrhagic fever. Lung tissues from 73 rodents (Apodemus agrarius coreae) gave specific immunofluorescent reactions when they reacted with sera from patients convalescing from Korean hemorrhagic fever. Similar staaining was observed in the lungs of A. agrarius inoculated with acute-phase sera obtained from two patients with this disease. The unidentified agent was successfully propagated in adult A. agrarius through eight passages representing a cumulative dilution of greater than 10(-17). Experimentally inoculated rodents developed specific fluorescent antigen in the lung, kidney, liver, parotid glands, and bladder. Organs, especially lungs, were positive beginning 10 days and continuing through 69 days after inoculation. The agent could not be cultivated in several types of cell cultures nor in laboratory animals. No fluorescence was observed when infected A. agrarius lung tissues were reacted with antisera to Marburg virus, Ebola virus, and serval arenaviruses. Diagnostic increases in immunofluorescent antibodies occurred in 113 of 116 severe and 11 of 34 milder cases of clinically suspected Korean hemorrhagic fever. Antibodies were present during the first week of symptoms, reached a peak at the end of the second week, and persisted for up to 14 years. Convalescent-phase sera from four persons suffering a similar disease in the Soviet Union were also positive for antibodies."}
{"id": "PMID:24674", "title": "Physician's assistants, their physician employers, and the problem of autonomy: consensus or conflict?", "content": "Do physician's assistants (PAs) and their physician employers disagree about levels of supervision and autonomy, and does level of physician's assistant autonomy relate in any way to other aspects of practice satisfaction? An indepth study of MD-PA teams in practice reveals that there is greater consensus than conflict concerning the autonomy of the physician's assistant; that the level of physician's assistant autonomy is not related to salary or to physician's assistant employment satisfaction; and that physician-employers who consider their physician's assistants to be more autonomous also tend to feel that the quality of their lives has improved as a result of hiring an assistant.", "contents": "Physician's assistants, their physician employers, and the problem of autonomy: consensus or conflict? Do physician's assistants (PAs) and their physician employers disagree about levels of supervision and autonomy, and does level of physician's assistant autonomy relate in any way to other aspects of practice satisfaction? An indepth study of MD-PA teams in practice reveals that there is greater consensus than conflict concerning the autonomy of the physician's assistant; that the level of physician's assistant autonomy is not related to salary or to physician's assistant employment satisfaction; and that physician-employers who consider their physician's assistants to be more autonomous also tend to feel that the quality of their lives has improved as a result of hiring an assistant."}
{"id": "PMID:24675", "title": "Nitrogenase synthesis in Klebsiella pneumoniae: comparison of ammonium and oxygen regulation.", "content": "Rates of nitrogenase synthesis by Klebsiella pneumoniae were measured by pulse-labelling organisms with a mixture of 14C-labelled amino acids followed by sodium dodecyl sulphate gel electrophoresis and autoradiography. Populations from an NH4+-repressed, SO42--limited chemostat (0.46 mg dry wt ml-1), when released from NH4+ repression, simultaneously synthesized detectable quantities of the three nitrogenase polypeptides 45 min before acetylene-reducing activity was observed. Exposure of populations synthesizing nitrogenase to air or NH4+ (200 microgram N ml-1) repressed synthesis of both component proteins simultaneously, the rate initially decreasing by half in 11 to 12 min; in the presence of NH4+ a second slower phase with an approximate half-life of 30 min was observed. With 5% O2 in N2 the half-lives for the decreases in the rates of synthesis were 30 min for the Fe protein and 33 min for the Mo-Fe protein. Oxygen also repressed nitrogenase in a glutamine synthetase constitutive derivative of K. pneumoniae (strain SK24) which escapes NH4+ repression. Regulation of nitrogenase by O2 may therefore be independent of glutamine synthetase.", "contents": "Nitrogenase synthesis in Klebsiella pneumoniae: comparison of ammonium and oxygen regulation. Rates of nitrogenase synthesis by Klebsiella pneumoniae were measured by pulse-labelling organisms with a mixture of 14C-labelled amino acids followed by sodium dodecyl sulphate gel electrophoresis and autoradiography. Populations from an NH4+-repressed, SO42--limited chemostat (0.46 mg dry wt ml-1), when released from NH4+ repression, simultaneously synthesized detectable quantities of the three nitrogenase polypeptides 45 min before acetylene-reducing activity was observed. Exposure of populations synthesizing nitrogenase to air or NH4+ (200 microgram N ml-1) repressed synthesis of both component proteins simultaneously, the rate initially decreasing by half in 11 to 12 min; in the presence of NH4+ a second slower phase with an approximate half-life of 30 min was observed. With 5% O2 in N2 the half-lives for the decreases in the rates of synthesis were 30 min for the Fe protein and 33 min for the Mo-Fe protein. Oxygen also repressed nitrogenase in a glutamine synthetase constitutive derivative of K. pneumoniae (strain SK24) which escapes NH4+ repression. Regulation of nitrogenase by O2 may therefore be independent of glutamine synthetase."}
{"id": "PMID:24676", "title": "Factors influencing the susceptibility of Candida albicans to the polyenoic antibiotics nystatin and amphotericin B.", "content": "Factors influencing the interaction between Candida albicans and the polyenoic antibiotics nystatin and amphotericin B have been investigated using a K+-specific electrode to measure polyene-mediated efflux of cellular K+. In batch cultures, sensitivity was a function of culture age. Using continuous (chemostat) cultures, the influence of growth-limiting substrate, specific growth rate, growth temperature and growth pH were examined. Carbon-limited cultures showed the highest sensitivity of those substrates tested, and susceptibility increased with growth rate. Within the range 22 to 42 degrees C, growth at lower temperatures resulted in increased sensitivity, whilst a similar trend was observed when the growth pH of cultures was reduced. Further, under the conditions tested, there were considerable variations in free intracellular K+ concentrations.", "contents": "Factors influencing the susceptibility of Candida albicans to the polyenoic antibiotics nystatin and amphotericin B. Factors influencing the interaction between Candida albicans and the polyenoic antibiotics nystatin and amphotericin B have been investigated using a K+-specific electrode to measure polyene-mediated efflux of cellular K+. In batch cultures, sensitivity was a function of culture age. Using continuous (chemostat) cultures, the influence of growth-limiting substrate, specific growth rate, growth temperature and growth pH were examined. Carbon-limited cultures showed the highest sensitivity of those substrates tested, and susceptibility increased with growth rate. Within the range 22 to 42 degrees C, growth at lower temperatures resulted in increased sensitivity, whilst a similar trend was observed when the growth pH of cultures was reduced. Further, under the conditions tested, there were considerable variations in free intracellular K+ concentrations."}
{"id": "PMID:24677", "title": "Cytoplasmic vacuoles of Rous virus transformed cells are organelles involved in cation uptake.", "content": "Cytoplasmic vacuoles induced during transformation of cells by Bryan strain Rous sarcoma virus (RSV-BH) have been studied using the cationic dye, neutral red(NR). Both the rate of uptake and the accumulation of NR are greater in RSV-BH transformed cells than non-transformed cells however, uptake was greater in vacuolated than in non-vacuolated cells, whether or not they were transformed. The NR was incorporated into pre-existing vacuoles in the absence of cytoplasmic staining, suggesting the existence of direct channels from the cell surface to the vacuoles. Other low mol. wt. cationic dyes could also be incorporated into vacuoles, although those with branched structures or cationic weights greater than 330 were excluded. No anionic dyes were incorporated. Infection of cells with a virus mutant, RSV-BH-Ta, induces temperature-dependent vacuolization. After a shift to the vacuole-permissive temperature, vacuoles developed at different rates and with morphological variations with different cations. Vacuoles which had formed in the presence of several cations, (K+, Rb+, tris+, choline+) failed to disappear when cells were incubated at a temperature sufficient to revert vacuoles formed in Na+-containing medium. No short-term effects of Cl-replacements (Br-, I-, or SO2-4) on vacuolization or reversal were observed. The results suggest that these vacuoles are organelles involved in cation uptake. A possible function for these organelles in RSV-BH induced malignancy is discussed.", "contents": "Cytoplasmic vacuoles of Rous virus transformed cells are organelles involved in cation uptake. Cytoplasmic vacuoles induced during transformation of cells by Bryan strain Rous sarcoma virus (RSV-BH) have been studied using the cationic dye, neutral red(NR). Both the rate of uptake and the accumulation of NR are greater in RSV-BH transformed cells than non-transformed cells however, uptake was greater in vacuolated than in non-vacuolated cells, whether or not they were transformed. The NR was incorporated into pre-existing vacuoles in the absence of cytoplasmic staining, suggesting the existence of direct channels from the cell surface to the vacuoles. Other low mol. wt. cationic dyes could also be incorporated into vacuoles, although those with branched structures or cationic weights greater than 330 were excluded. No anionic dyes were incorporated. Infection of cells with a virus mutant, RSV-BH-Ta, induces temperature-dependent vacuolization. After a shift to the vacuole-permissive temperature, vacuoles developed at different rates and with morphological variations with different cations. Vacuoles which had formed in the presence of several cations, (K+, Rb+, tris+, choline+) failed to disappear when cells were incubated at a temperature sufficient to revert vacuoles formed in Na+-containing medium. No short-term effects of Cl-replacements (Br-, I-, or SO2-4) on vacuolization or reversal were observed. The results suggest that these vacuoles are organelles involved in cation uptake. A possible function for these organelles in RSV-BH induced malignancy is discussed."}
{"id": "PMID:24678", "title": "Growth hormone and prolactin response to bromocriptine in patients with Huntington's chorea.", "content": "The growth hormone (hGH) and prolactin (hPRL) responses to oral bromocriptine were studied in two groups of patients with Huntington's chorea and in seven healthy control subjects. The patients included six patients who had previously been treated with phenothiazines and six patients who had not received phenothiazine treatment. All medication was stopped 72 hours before the investigation which involved taking blood samples for up to 210 minutes after taking bromocriptine (2.5 mg). Plasma samples were analysed for hGH and hPRL. There was no significant difference in basal hGH concentrations between the patients and control subjects. The hGH response to bromocriptine varied in the individual patients but the concentrations were significantly lower in the patients compared with the controls between 160 and 210 minutes. The basal concentrations of hPRL were also not different, apart from the findings of elevated hPRL concentrations in three patients previously treated with phenothiazines. The patients and control subjects showed a consistent fall in hPRL concentrations after taking bromocriptine. The lower peak hGH response to bromocriptine found in the patients suggests that there may be an alteration of dopaminergic neurones mediating hGH release.", "contents": "Growth hormone and prolactin response to bromocriptine in patients with Huntington's chorea. The growth hormone (hGH) and prolactin (hPRL) responses to oral bromocriptine were studied in two groups of patients with Huntington's chorea and in seven healthy control subjects. The patients included six patients who had previously been treated with phenothiazines and six patients who had not received phenothiazine treatment. All medication was stopped 72 hours before the investigation which involved taking blood samples for up to 210 minutes after taking bromocriptine (2.5 mg). Plasma samples were analysed for hGH and hPRL. There was no significant difference in basal hGH concentrations between the patients and control subjects. The hGH response to bromocriptine varied in the individual patients but the concentrations were significantly lower in the patients compared with the controls between 160 and 210 minutes. The basal concentrations of hPRL were also not different, apart from the findings of elevated hPRL concentrations in three patients previously treated with phenothiazines. The patients and control subjects showed a consistent fall in hPRL concentrations after taking bromocriptine. The lower peak hGH response to bromocriptine found in the patients suggests that there may be an alteration of dopaminergic neurones mediating hGH release."}
{"id": "PMID:24680", "title": "Influence of dietary biotin level on growth, metabolism and pathology of rainbow trout.", "content": "Supplementation of a dry diet containing herring and soybean meals with D biotin had no effect on the feed comsumption, growth or mortality of rainbow trout in a 28 week experiment. In a second experiment two series of diets were used: practical, based upon herring  and soybean meals, and purified, based upon casein and gelatin. The basal levels of biotin in the two series of diets were: 0.51 and 0 mg/kg, respectively. There were four treatment groups in each of the two diet series: the practical diets were either supplemented with 0.5 mg D biotin/kg or 10% of either raw or heated egg white was added to the diet. The purified diets were supplemented with graded levels of D biotin (0, 0.25 0.5, or 1.0 mg/kg). Raw egg white (1%) was added to the biotin unsupplemented diet. Feeding these diets to rainbow trout for 24 weeks showed that both the practical diet containing egg white, and the unsupplemented, purified diet were biotin deficient, all the other diets contained adequate amounts of biotin to support growth and prevent mortality. Neither supplementation of the practical diet nor adding more than 0.25 mg D biotin/kg to the purified diet resulted in any improvement in growth however the biotin levels in the livers were greater for the fish which had received the higher levels of dietary biotin, but these increased levels of biotin did not influence the activity of acetyl CoA carboxylase. The biotin deficient fish were anorexic, and exhibited degeneration of the gills: shortening and thickening of the lamellae and hypertrophy and hyperplasia of the heterogenous epithelial cells of the lamellae.", "contents": "Influence of dietary biotin level on growth, metabolism and pathology of rainbow trout. Supplementation of a dry diet containing herring and soybean meals with D biotin had no effect on the feed comsumption, growth or mortality of rainbow trout in a 28 week experiment. In a second experiment two series of diets were used: practical, based upon herring  and soybean meals, and purified, based upon casein and gelatin. The basal levels of biotin in the two series of diets were: 0.51 and 0 mg/kg, respectively. There were four treatment groups in each of the two diet series: the practical diets were either supplemented with 0.5 mg D biotin/kg or 10% of either raw or heated egg white was added to the diet. The purified diets were supplemented with graded levels of D biotin (0, 0.25 0.5, or 1.0 mg/kg). Raw egg white (1%) was added to the biotin unsupplemented diet. Feeding these diets to rainbow trout for 24 weeks showed that both the practical diet containing egg white, and the unsupplemented, purified diet were biotin deficient, all the other diets contained adequate amounts of biotin to support growth and prevent mortality. Neither supplementation of the practical diet nor adding more than 0.25 mg D biotin/kg to the purified diet resulted in any improvement in growth however the biotin levels in the livers were greater for the fish which had received the higher levels of dietary biotin, but these increased levels of biotin did not influence the activity of acetyl CoA carboxylase. The biotin deficient fish were anorexic, and exhibited degeneration of the gills: shortening and thickening of the lamellae and hypertrophy and hyperplasia of the heterogenous epithelial cells of the lamellae."}
{"id": "PMID:24685", "title": "A membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the beta-blocking drugs atenolol and propranolol.", "content": "The buccal absorption characteristics and physicochemical properties of the beta-adrenoceptor blocking agents propranolol and atenolol have been investigated to evaluate their permeation properties across biological lipid membranes. The dissociation constants, solubilities of free base, and n-heptane partition coefficients show that propranolol in its unionized form is much more lipophilic than atenolol, both drugs being bases with a similar pKa. Buccal absorption was studied under conditions of varying drug concentration, contact time, and pH, and controlled through the use of a non-absorbable marker. The absorption findings are in general agreement with the pH-partition theory. A new compartmental diffusional model that includes membrane storage and a hypothetical \"aqueous pH-buffering surfaces system\" allowed a more exhaustive interpretation to be made. A method for the estimation of the intrinsic pH and buffer capacity of the postulated surface system from drug pH-absorption data and partition coefficients alone is described. With human oral mucosa the intrinsic pH was near 6.7, and the buffering capacity of the system (expressed as the ratio deltapH/deltapH eff) about 2.86. The method was validated using published absorption data from the rat small intestine. Absorption of unionized drug through pores is shown to be negligible in the buccal absorption situation. The time course of absorption suggests membrane storage of lipophilic compounds; the in vivo partition coefficient of unionized propranolol relative to the mucous membrane could be calculated for the peusdo-steady state of absorption, i.e. the partition equilibrium between mouth content and membrane, to be approximately 776; this value is of the same order as the in vitro partition coefficient for the erythrocyte/plasma system. The lipid biophase of the buccal membrane is estimated semiquantitatively to be of intermediate polarity (epsilon = 3-4).", "contents": "A membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the beta-blocking drugs atenolol and propranolol. The buccal absorption characteristics and physicochemical properties of the beta-adrenoceptor blocking agents propranolol and atenolol have been investigated to evaluate their permeation properties across biological lipid membranes. The dissociation constants, solubilities of free base, and n-heptane partition coefficients show that propranolol in its unionized form is much more lipophilic than atenolol, both drugs being bases with a similar pKa. Buccal absorption was studied under conditions of varying drug concentration, contact time, and pH, and controlled through the use of a non-absorbable marker. The absorption findings are in general agreement with the pH-partition theory. A new compartmental diffusional model that includes membrane storage and a hypothetical \"aqueous pH-buffering surfaces system\" allowed a more exhaustive interpretation to be made. A method for the estimation of the intrinsic pH and buffer capacity of the postulated surface system from drug pH-absorption data and partition coefficients alone is described. With human oral mucosa the intrinsic pH was near 6.7, and the buffering capacity of the system (expressed as the ratio deltapH/deltapH eff) about 2.86. The method was validated using published absorption data from the rat small intestine. Absorption of unionized drug through pores is shown to be negligible in the buccal absorption situation. The time course of absorption suggests membrane storage of lipophilic compounds; the in vivo partition coefficient of unionized propranolol relative to the mucous membrane could be calculated for the peusdo-steady state of absorption, i.e. the partition equilibrium between mouth content and membrane, to be approximately 776; this value is of the same order as the in vitro partition coefficient for the erythrocyte/plasma system. The lipid biophase of the buccal membrane is estimated semiquantitatively to be of intermediate polarity (epsilon = 3-4)."}
{"id": "PMID:24686", "title": "Biopharmaceutical properties of liquid and tablet antacids: in vivo studies using the intragastric pH-measurement technique.", "content": "Three types of liquid and tablet antacids have been studied in vitro and in vivo: aluminium hydroxide, aluminium hydroxide-magnesium carbonate and hydrotalcite. The effects on gastric pH of antacid suspensions and antacid chewing tablets having identical active ingredients have been studied in 36 volunteers, the sequence of both forms of administration being randomized. Gastric acid secretion was continuously stimulated during the experiment by a pentagastrin infusion. Antacid chewing tablets gave inferior results when compared with the same antacid in liquid. Antacid suspensions are therefore preferred in the treatment of acid-peptic disease.", "contents": "Biopharmaceutical properties of liquid and tablet antacids: in vivo studies using the intragastric pH-measurement technique. Three types of liquid and tablet antacids have been studied in vitro and in vivo: aluminium hydroxide, aluminium hydroxide-magnesium carbonate and hydrotalcite. The effects on gastric pH of antacid suspensions and antacid chewing tablets having identical active ingredients have been studied in 36 volunteers, the sequence of both forms of administration being randomized. Gastric acid secretion was continuously stimulated during the experiment by a pentagastrin infusion. Antacid chewing tablets gave inferior results when compared with the same antacid in liquid. Antacid suspensions are therefore preferred in the treatment of acid-peptic disease."}
{"id": "PMID:24687", "title": "The diffusion of nandrolone through occluded and non-occluded human skin.", "content": "Diffusion constants have been measured for nandrolone in human cadaver skin in vitro under conditions which approximate to both the occluded and non-occluded topical therapeutic situation. The results suggest that occlusion affects the diffusion parameters only marginally, if at all, but appears to reduce the ability of the stratum corneum to \"irreversibly\" bind a fraction of the applied dose. Studies of nandrolone diffusion in freshly excised human epidermis yield similar results to those from measurements on cadaver skin, and it has also been found that epidermal samples excised from non-involved sites of human psoriatic patients behave under these conditions in essentially the same way as normal epidermis.", "contents": "The diffusion of nandrolone through occluded and non-occluded human skin. Diffusion constants have been measured for nandrolone in human cadaver skin in vitro under conditions which approximate to both the occluded and non-occluded topical therapeutic situation. The results suggest that occlusion affects the diffusion parameters only marginally, if at all, but appears to reduce the ability of the stratum corneum to \"irreversibly\" bind a fraction of the applied dose. Studies of nandrolone diffusion in freshly excised human epidermis yield similar results to those from measurements on cadaver skin, and it has also been found that epidermal samples excised from non-involved sites of human psoriatic patients behave under these conditions in essentially the same way as normal epidermis."}
{"id": "PMID:24688", "title": "Circling behaviour in the rat following unilateral injections of p-chlorophenylalanine and ethanolamine-O-sulphate into the substantia nigra.", "content": "Circling behaviour following the unilateral intranigral injection of the gamma-aminobutyric acid (GABA) transaminase inhibitor ethanolamine-O-sulphate, (EOS), or the tryptophan hydroxylase inhibitor p-chlorophenylalanine (pCPA) was compared, both for spontaneous circling and for circling induced by apomorphine administration. EOS-injected rats exhibited spontaneous contralateral rotation for up to 3 h after such injections. pCPA-injected rats showed only a slight ipsilateral postural asymmetry, both groups of rats elicited ipsilateral rotation upon apomorphine challenge. Increased ipsilateral dopamine release within the corpus striatrum accompanied this response. It is proposed that GABA and 5-HT may be closely related in modifying the nigrostriatal impulse flow.", "contents": "Circling behaviour in the rat following unilateral injections of p-chlorophenylalanine and ethanolamine-O-sulphate into the substantia nigra. Circling behaviour following the unilateral intranigral injection of the gamma-aminobutyric acid (GABA) transaminase inhibitor ethanolamine-O-sulphate, (EOS), or the tryptophan hydroxylase inhibitor p-chlorophenylalanine (pCPA) was compared, both for spontaneous circling and for circling induced by apomorphine administration. EOS-injected rats exhibited spontaneous contralateral rotation for up to 3 h after such injections. pCPA-injected rats showed only a slight ipsilateral postural asymmetry, both groups of rats elicited ipsilateral rotation upon apomorphine challenge. Increased ipsilateral dopamine release within the corpus striatrum accompanied this response. It is proposed that GABA and 5-HT may be closely related in modifying the nigrostriatal impulse flow."}
{"id": "PMID:24689", "title": "Dopamine-beta-hydroxylase release following acute selective sympathetic nerve stimulation of the heart, spleen and mesentery.", "content": "In increase in the concentration of dopamine-beta-hydroxylase (DBH) in the blood perfusates of the heart, spleen and mesentery of pithed rats was detected following selective sympathetic nerve stimulation. Furthermore, the concentration of enzyme released by each organ correlated with the stimulation frequency. The results provide further corroborative evidence that the concentration of DBH in the plasma is related to the degree of sympathetic tone. If the sampling methods described were applied to non-spinalized animals, the concentrations of DBH in organ perfusates could be used as an index of sympathetic nervous tone and thus provide a useful preparation for the study of drugs on the sympathetic nervous system.", "contents": "Dopamine-beta-hydroxylase release following acute selective sympathetic nerve stimulation of the heart, spleen and mesentery. In increase in the concentration of dopamine-beta-hydroxylase (DBH) in the blood perfusates of the heart, spleen and mesentery of pithed rats was detected following selective sympathetic nerve stimulation. Furthermore, the concentration of enzyme released by each organ correlated with the stimulation frequency. The results provide further corroborative evidence that the concentration of DBH in the plasma is related to the degree of sympathetic tone. If the sampling methods described were applied to non-spinalized animals, the concentrations of DBH in organ perfusates could be used as an index of sympathetic nervous tone and thus provide a useful preparation for the study of drugs on the sympathetic nervous system."}
{"id": "PMID:24690", "title": "Possible differences in alpha-adrenoceptors in rabbit ileum and spleen.", "content": "In isolated tissues from reserpinized rabbits (5 mg kg-1, i.m. 20 h before experiment) and in the presence of cocaine (3 x 10(-5) M), corticosterone (2.8 x 10(-5)M), tropolone (3 x 10(-5) M), propranolol (4 x 10(-5)M) and disodium EDTA (3 X 10(-5)M), the potency ratios (relative to (-)-noradrenaline) of (-)adrenaline, (-)-phenylephrine and (+/-)-methoxamine were (m+/-s.e.) 2.03 +/- 0.13, 0.045 +/- 0.003 and 0.0062 +/- 0.0018 respectively in splenic strips and 1.77 +/- 0.41, 0.093 +/- 0.018 and 0.029 +/- 0.004 respectively in isolated ileum. Although the pA2 values for phentolamine and thymoxamine against (-)-noradrenaline in the two tissues were very similar there was a statistically significant difference when using yohimbine as the alpha-adrenoceptor blocking agent (pA2 = 6.80 +/- 0.30 in spleen; 5.60 +/- 0.12 in ileum). These differences suggest that the alpha-adrenoceptor in the two tissues is not identical. The pA2 value of phentolamine in rabbits ileum was not significantly different whether (-)noradrenaline or (+/-) methoxamine was used as agonist (7.91 +/- 0.07 and 7.97 +/- 0.06 respectively) while that of yohimbine was 5.56 +/- 0.10 using (-)noradrenaline and 6.19 +/- 0.12 using (+/-)methoxamine. In the light of this latter result and, considering the scatter of the experimentally determined values, there may be two alpha-adrenoceptors in rabbit ileum and either or both may not be identical in all respects to the alpha-adrenoceptor found in rabbit spleen.", "contents": "Possible differences in alpha-adrenoceptors in rabbit ileum and spleen. In isolated tissues from reserpinized rabbits (5 mg kg-1, i.m. 20 h before experiment) and in the presence of cocaine (3 x 10(-5) M), corticosterone (2.8 x 10(-5)M), tropolone (3 x 10(-5) M), propranolol (4 x 10(-5)M) and disodium EDTA (3 X 10(-5)M), the potency ratios (relative to (-)-noradrenaline) of (-)adrenaline, (-)-phenylephrine and (+/-)-methoxamine were (m+/-s.e.) 2.03 +/- 0.13, 0.045 +/- 0.003 and 0.0062 +/- 0.0018 respectively in splenic strips and 1.77 +/- 0.41, 0.093 +/- 0.018 and 0.029 +/- 0.004 respectively in isolated ileum. Although the pA2 values for phentolamine and thymoxamine against (-)-noradrenaline in the two tissues were very similar there was a statistically significant difference when using yohimbine as the alpha-adrenoceptor blocking agent (pA2 = 6.80 +/- 0.30 in spleen; 5.60 +/- 0.12 in ileum). These differences suggest that the alpha-adrenoceptor in the two tissues is not identical. The pA2 value of phentolamine in rabbits ileum was not significantly different whether (-)noradrenaline or (+/-) methoxamine was used as agonist (7.91 +/- 0.07 and 7.97 +/- 0.06 respectively) while that of yohimbine was 5.56 +/- 0.10 using (-)noradrenaline and 6.19 +/- 0.12 using (+/-)methoxamine. In the light of this latter result and, considering the scatter of the experimentally determined values, there may be two alpha-adrenoceptors in rabbit ileum and either or both may not be identical in all respects to the alpha-adrenoceptor found in rabbit spleen."}
{"id": "PMID:24691", "title": "The synthesis and urinary estimation of N-hydroxyaprobarbitone.", "content": "N-Hydroxyaprobarbitone (I) has been synthesized by oxidation of aprobarbitone, characterized, and a method developed for its estimation in urine. It has shown to be no more than a minor metabolite (less than 4%) in the human metabolism of aprobarbitone.", "contents": "The synthesis and urinary estimation of N-hydroxyaprobarbitone. N-Hydroxyaprobarbitone (I) has been synthesized by oxidation of aprobarbitone, characterized, and a method developed for its estimation in urine. It has shown to be no more than a minor metabolite (less than 4%) in the human metabolism of aprobarbitone."}
{"id": "PMID:24692", "title": "Aggregation of antidepressant drugs in aqueous solution.", "content": "Light scattering, conductivity and pH methods have been used to examine the aggregation in aqueous solution of a series of antidepressant drugs. The drugs investigated included the hydrochlorides of amitriptyline, butriptyline, protriptyline, nortriptyline, imipramine, desipramine, clomipramine, dothiepin, dibenzepin, opipramol, iprindole, doxepin, mianserin and maprotiline. No significant association of dibenzepin, mianserin or maprotiline hydrochlorides could be detected up to their respective solubility limits. A micellar pattern of association was established for all other compounds. Critical micelle concentrations and micellar properties are reported.", "contents": "Aggregation of antidepressant drugs in aqueous solution. Light scattering, conductivity and pH methods have been used to examine the aggregation in aqueous solution of a series of antidepressant drugs. The drugs investigated included the hydrochlorides of amitriptyline, butriptyline, protriptyline, nortriptyline, imipramine, desipramine, clomipramine, dothiepin, dibenzepin, opipramol, iprindole, doxepin, mianserin and maprotiline. No significant association of dibenzepin, mianserin or maprotiline hydrochlorides could be detected up to their respective solubility limits. A micellar pattern of association was established for all other compounds. Critical micelle concentrations and micellar properties are reported."}
{"id": "PMID:24706", "title": "Formation of liquid crystal and other non-fluid phases in emulsions containing non-ionic surfactants.", "content": "The relation between the phase distribution of components and the nature and properties of dispersions formed in a four-component system containing dodecane, water and two homogeneous non-ionic surfactants has been investigated by phase-rule techniques. Phase equilibrium diagrams for the four ternary systems were investigated and the phase boundaries for the various regions formed in these systems were defined by synthetic and analytical methods. In some of the ternary diagrams a narrow three-phase region occurs where 'gel' or liquid crystal as well as two isotropic liquid phases are present. Dispersions containing the gel phase were very stable. The four-component system has not been fully investigated due to the presence of extensive liquid crystal phases and three-phase regions. However, some distribution data for the quaternary system was obtained. In the presence of sufficient amounts of the short chain non-ionic surfactant C10H21(O.CH2.CH2)3OH, a three-liquid phase region occurs where multiple drops readily form.", "contents": "Formation of liquid crystal and other non-fluid phases in emulsions containing non-ionic surfactants. The relation between the phase distribution of components and the nature and properties of dispersions formed in a four-component system containing dodecane, water and two homogeneous non-ionic surfactants has been investigated by phase-rule techniques. Phase equilibrium diagrams for the four ternary systems were investigated and the phase boundaries for the various regions formed in these systems were defined by synthetic and analytical methods. In some of the ternary diagrams a narrow three-phase region occurs where 'gel' or liquid crystal as well as two isotropic liquid phases are present. Dispersions containing the gel phase were very stable. The four-component system has not been fully investigated due to the presence of extensive liquid crystal phases and three-phase regions. However, some distribution data for the quaternary system was obtained. In the presence of sufficient amounts of the short chain non-ionic surfactant C10H21(O.CH2.CH2)3OH, a three-liquid phase region occurs where multiple drops readily form."}
{"id": "PMID:24707", "title": "Factors affecting the disintegration and dissolution of chloroquine phosphate/starch tablets.", "content": "A study has been made of the effects produced on the disintegration and dissolution times of chloroquine phosphate tablets by varying their moisture and starch contents and the distribution of the starch in the formulation. 3 to 5% w/w of moisture produces a maximum in the disintegration and dissolution times. Starch added externally as a powder acts only as a disintegrating agent for the tablets, but starch added internally as a paste during granulation acts both as a binding agent and a disintegrant.", "contents": "Factors affecting the disintegration and dissolution of chloroquine phosphate/starch tablets. A study has been made of the effects produced on the disintegration and dissolution times of chloroquine phosphate tablets by varying their moisture and starch contents and the distribution of the starch in the formulation. 3 to 5% w/w of moisture produces a maximum in the disintegration and dissolution times. Starch added externally as a powder acts only as a disintegrating agent for the tablets, but starch added internally as a paste during granulation acts both as a binding agent and a disintegrant."}
{"id": "PMID:24708", "title": "Control of the composition of gentamicin sulphate by proton magnetic resonance spectrometry.", "content": "The proportions of the main components present in gentamicin sulphate complex, gentamicins C1, C1a and C2, can be monitored by 1H nuclear magnetic resonance (nmr) spectrometry. The method depends on measurement of the peak heights of signals for N-methyl and C-methyl groups present in all three components and of those present in C1 and C2 only, followed by calculation of peak height ratios to control composition within acceptable limits. The precision and reproducibility of the method have been established through two collaborative studies each involving seven laboratories. In the second study, with an improved procedure, the mean variance between laboratories with 10 samples was 3.4 X 10(-4) for the N-methyl ratio of the peak at delta 2.75 to that at delta 2.95, and 1.25 X 10(-3) for the C-methyl ratio of the peak at delta 1.25 to that at delta 1.35. Within laboratories the mean variance for triplicate determinations was 7.4 X 10(-5) and 8.9 X 10(-5) respectively. The data presented here form the experimental basis for the test controlling the composition of gentamicin sulphate in the British Pharmacopoeia 1973: Addendum 1975, and for the introduction into the British Pharmacopoeia of nmr spectrometry as an analytical technique. The reference standards and all batches of gentamicin sulphate intended for therapeutic use in the United Kingdom examined by this procedure comply with the limits laid down.", "contents": "Control of the composition of gentamicin sulphate by proton magnetic resonance spectrometry. The proportions of the main components present in gentamicin sulphate complex, gentamicins C1, C1a and C2, can be monitored by 1H nuclear magnetic resonance (nmr) spectrometry. The method depends on measurement of the peak heights of signals for N-methyl and C-methyl groups present in all three components and of those present in C1 and C2 only, followed by calculation of peak height ratios to control composition within acceptable limits. The precision and reproducibility of the method have been established through two collaborative studies each involving seven laboratories. In the second study, with an improved procedure, the mean variance between laboratories with 10 samples was 3.4 X 10(-4) for the N-methyl ratio of the peak at delta 2.75 to that at delta 2.95, and 1.25 X 10(-3) for the C-methyl ratio of the peak at delta 1.25 to that at delta 1.35. Within laboratories the mean variance for triplicate determinations was 7.4 X 10(-5) and 8.9 X 10(-5) respectively. The data presented here form the experimental basis for the test controlling the composition of gentamicin sulphate in the British Pharmacopoeia 1973: Addendum 1975, and for the introduction into the British Pharmacopoeia of nmr spectrometry as an analytical technique. The reference standards and all batches of gentamicin sulphate intended for therapeutic use in the United Kingdom examined by this procedure comply with the limits laid down."}
{"id": "PMID:24709", "title": "Isolation and identification of the fluorescent degradation product of some beta-lactam antibiotics.", "content": "A fluorescent degradation product of cephalexin, recently employed in the determination of this antibiotic in aqueous solution and human plasma, has been isolated and identified as 2-hydroxy-3-phenyl-6-methylpyrazine. Spectroscopically and chromatographically the product is indistinguishable from  that obtained by the same method from a series of other cephalosporins and penicillins bearing an alpha-amino group on the side-chain, and from the pyrazine structure produced by synthesis. Two reported methods for the fluorimetric determination of ampicillin have also been found to yield the same degradation product and not the suggested diketopiperazine structure.", "contents": "Isolation and identification of the fluorescent degradation product of some beta-lactam antibiotics. A fluorescent degradation product of cephalexin, recently employed in the determination of this antibiotic in aqueous solution and human plasma, has been isolated and identified as 2-hydroxy-3-phenyl-6-methylpyrazine. Spectroscopically and chromatographically the product is indistinguishable from  that obtained by the same method from a series of other cephalosporins and penicillins bearing an alpha-amino group on the side-chain, and from the pyrazine structure produced by synthesis. Two reported methods for the fluorimetric determination of ampicillin have also been found to yield the same degradation product and not the suggested diketopiperazine structure."}
{"id": "PMID:24710", "title": "Survival of plasmid-containing strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus in phenylmercuric nitrate and thiomersal.", "content": "Strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus harbouring plasmids that confer mercury resistance grew in nutrient broth containing concentrations of phenylmercuric nitrate (PMN) that were inhibitory to isogenic plasmid-less strains. Decimal reduction times of P. aeruginosa and S. aureus in aqueous PMN solution were also increased by the presence of plasmids. The viable count of a plasmid-containing P. aeruginosa strain in Davis and Mingioli's minimal medium (DM) containing 10 microgram ml-1 PMN fell by approximately 99% after 5 h. The count then remained constant for two weeks, when growth recommenced. This pattern of death followed by growth was also observed with the P. aeruginosa strain in DM + 10 microgram ml-1 thiomersal.", "contents": "Survival of plasmid-containing strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus in phenylmercuric nitrate and thiomersal. Strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus harbouring plasmids that confer mercury resistance grew in nutrient broth containing concentrations of phenylmercuric nitrate (PMN) that were inhibitory to isogenic plasmid-less strains. Decimal reduction times of P. aeruginosa and S. aureus in aqueous PMN solution were also increased by the presence of plasmids. The viable count of a plasmid-containing P. aeruginosa strain in Davis and Mingioli's minimal medium (DM) containing 10 microgram ml-1 PMN fell by approximately 99% after 5 h. The count then remained constant for two weeks, when growth recommenced. This pattern of death followed by growth was also observed with the P. aeruginosa strain in DM + 10 microgram ml-1 thiomersal."}
{"id": "PMID:24711", "title": "Melanocyte-stimulating hormone--mimetic action of the phenothiazines.", "content": "We have compared the melanophore-stimulating action of four phenothiazines, trifluoperazine, perphenazine, chlorpromazine, and prochlorperazine, with alpha-MSH on the skin of the lizard Anolis carolinensis, using a new rate method of bioassay. The dose-response curves for the phenothiazines were parallel to that of alpha-MSH, and when given together alpha-MSH and chlorpromazine were additive. The phenothiazines may therefore stimulate melanosome dispersion in the lizard skin by the same mechanism as alpha-MSH; a MSH-mimetic action of phenothiazines may similarly explain their pigmentary action in man. The pigmentary potency of the phenothiazines corresponded with their therapeutic potency in man; this is in keeping with a neuro-regulatory role for MSH peptides and suggests a possible therapeutic use for them.", "contents": "Melanocyte-stimulating hormone--mimetic action of the phenothiazines. We have compared the melanophore-stimulating action of four phenothiazines, trifluoperazine, perphenazine, chlorpromazine, and prochlorperazine, with alpha-MSH on the skin of the lizard Anolis carolinensis, using a new rate method of bioassay. The dose-response curves for the phenothiazines were parallel to that of alpha-MSH, and when given together alpha-MSH and chlorpromazine were additive. The phenothiazines may therefore stimulate melanosome dispersion in the lizard skin by the same mechanism as alpha-MSH; a MSH-mimetic action of phenothiazines may similarly explain their pigmentary action in man. The pigmentary potency of the phenothiazines corresponded with their therapeutic potency in man; this is in keeping with a neuro-regulatory role for MSH peptides and suggests a possible therapeutic use for them."}
{"id": "PMID:24712", "title": "The effect of various topical antibiotic and antibacterial agents on the middle and inner ear of the guinea-pig.", "content": "The topical application of antibiotics and anti-inflammatory agents is used to reduce inflammation of the middle ear mucosa and irradicate infection. Many of the antibiotic and anti-inflammatory preparations so used contain compounds known to be or are potentially ototoxic. Eighteen antibiotic, antibacterial, antifungal and anti-inflammatory compounds and four commonly used solvents were screened for the absence of ototoxicity and inflammation to the middle ear mucosa. All compounds were injected intra-tympanically and sensory hair cells loss recorded graphically. Inflammation of the middle ear mucosa was assessed macroscopically. Of the 18 compounds only three, penicillin, carbenicillin and nystatin were free of hair cell toxicity and inflammatory effects on the middle ear mucosa. Only one of the commonly used solvents was free of side effects.", "contents": "The effect of various topical antibiotic and antibacterial agents on the middle and inner ear of the guinea-pig. The topical application of antibiotics and anti-inflammatory agents is used to reduce inflammation of the middle ear mucosa and irradicate infection. Many of the antibiotic and anti-inflammatory preparations so used contain compounds known to be or are potentially ototoxic. Eighteen antibiotic, antibacterial, antifungal and anti-inflammatory compounds and four commonly used solvents were screened for the absence of ototoxicity and inflammation to the middle ear mucosa. All compounds were injected intra-tympanically and sensory hair cells loss recorded graphically. Inflammation of the middle ear mucosa was assessed macroscopically. Of the 18 compounds only three, penicillin, carbenicillin and nystatin were free of hair cell toxicity and inflammatory effects on the middle ear mucosa. Only one of the commonly used solvents was free of side effects."}
{"id": "PMID:24713", "title": "Fate of [14C]warfarin in guinea-pigs: effect of a concomitant single dose of salicylate.", "content": "When a single dose of sodium salicylate (177.8 mg kg-1, by mouth) was given with [14C] warfarin (1 mg kg-1, i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14C for 6 h. At 1 h, salicylate increased the distribution of 14C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14C in the first 5 h after salicylate and a decrease in 14C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [14C]warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin.", "contents": "Fate of [14C]warfarin in guinea-pigs: effect of a concomitant single dose of salicylate. When a single dose of sodium salicylate (177.8 mg kg-1, by mouth) was given with [14C] warfarin (1 mg kg-1, i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14C for 6 h. At 1 h, salicylate increased the distribution of 14C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14C in the first 5 h after salicylate and a decrease in 14C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [14C]warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin."}
{"id": "PMID:24714", "title": "Inhibitors of gastric lesions in the rat.", "content": "The production by stress of gastric lesions in rats was inhibited by metiamide and by mepyramine. Lesions induced by indomethacin treatment were inhibited by mepyramine but not by metiamide. Those induced by aspirin treatment in pylorus-ligated rats were not affected by either antihistamine drug. Oral glutamine inhibited lesion production in all three systems whereas aspirin orally markedly potentiated it. Sodium salicylate inhibited both indomethacin-induced lesions and those produced by aspirin in pylorus-ligated rats. On the other hand, copper salicylate inhibited stress-induced lesions and it, like copper aspirinate, also markedly reduced the extent of lesions produced by aspirin. On the basis of these results, stress-induced lesion production offers a suitable animal model for testing anti-ulcer drugs as it is, like most human gastric ulcers, inhibited by H2-receptor inhibitors like metiamide.", "contents": "Inhibitors of gastric lesions in the rat. The production by stress of gastric lesions in rats was inhibited by metiamide and by mepyramine. Lesions induced by indomethacin treatment were inhibited by mepyramine but not by metiamide. Those induced by aspirin treatment in pylorus-ligated rats were not affected by either antihistamine drug. Oral glutamine inhibited lesion production in all three systems whereas aspirin orally markedly potentiated it. Sodium salicylate inhibited both indomethacin-induced lesions and those produced by aspirin in pylorus-ligated rats. On the other hand, copper salicylate inhibited stress-induced lesions and it, like copper aspirinate, also markedly reduced the extent of lesions produced by aspirin. On the basis of these results, stress-induced lesion production offers a suitable animal model for testing anti-ulcer drugs as it is, like most human gastric ulcers, inhibited by H2-receptor inhibitors like metiamide."}
{"id": "PMID:24729", "title": "Effects of catecholamine depleting drugs and d-amphetamine on self-stimulation of the substantia nigra and locus coeruleus.", "content": "6-Hydroxydopamine treatments which preferentially depleted either norepinephrine or dopamine were used to define the importance of these transmitter systems in the behavioral alterations produced by catecholamine synthesis inhibitors and d-amphetamine on self-stimulation of the locus coeruleus and substantia nigra. After chronic reduction of brain dopamine, an acute depression of self-stimulation of both the locus coeruleus and substantia nigra occurred. Preferential depletion of norepinephrine with 6-hydroxydopamine did not result in a significant decrease in self-stimulation of locus coeruleus or substantia nigra. However, a dose of alpha-methyltyrosine wihch had no effect in control rats or in rats with brain norepinephrine depleted caused a significant reduction in responding at both electrode placements in animals depleted of brain dopamine. Administration of U-14,624 affected neither substantia nigra nor locus coeruleus self-stimulation, even though it produced an additional 70% depletion of norepinephrine. When d-amphetamine sulfate was given to 6-hydroxydopamine-treated rats, the facilitation of self-stimulation produced by this compound was significantly attenuated in rats with prior depletion of brain dopamine. Depletion of brain norepinephrine did not affect the actions of d-amphetamine on self-stimulation. In other experiments, the actions of d-amphetamine to increase self-stimulation of animals pretreated with reserpine was found to be antagonized by alpha-methyltyrosine but not by U-14,624. Results suggest that drugs can alter self-stimulation of a site in brain anatomically associated with noradrenergic neural pathways and self-stimulation of a site primarily associated with dopaminergic pathways in a similar manner. These data also provided evidence for the involvement of dopamine fibers in the pharmacological actions of d-amphetamine, reserpine and alpha-methyltyrosine.", "contents": "Effects of catecholamine depleting drugs and d-amphetamine on self-stimulation of the substantia nigra and locus coeruleus. 6-Hydroxydopamine treatments which preferentially depleted either norepinephrine or dopamine were used to define the importance of these transmitter systems in the behavioral alterations produced by catecholamine synthesis inhibitors and d-amphetamine on self-stimulation of the locus coeruleus and substantia nigra. After chronic reduction of brain dopamine, an acute depression of self-stimulation of both the locus coeruleus and substantia nigra occurred. Preferential depletion of norepinephrine with 6-hydroxydopamine did not result in a significant decrease in self-stimulation of locus coeruleus or substantia nigra. However, a dose of alpha-methyltyrosine wihch had no effect in control rats or in rats with brain norepinephrine depleted caused a significant reduction in responding at both electrode placements in animals depleted of brain dopamine. Administration of U-14,624 affected neither substantia nigra nor locus coeruleus self-stimulation, even though it produced an additional 70% depletion of norepinephrine. When d-amphetamine sulfate was given to 6-hydroxydopamine-treated rats, the facilitation of self-stimulation produced by this compound was significantly attenuated in rats with prior depletion of brain dopamine. Depletion of brain norepinephrine did not affect the actions of d-amphetamine on self-stimulation. In other experiments, the actions of d-amphetamine to increase self-stimulation of animals pretreated with reserpine was found to be antagonized by alpha-methyltyrosine but not by U-14,624. Results suggest that drugs can alter self-stimulation of a site in brain anatomically associated with noradrenergic neural pathways and self-stimulation of a site primarily associated with dopaminergic pathways in a similar manner. These data also provided evidence for the involvement of dopamine fibers in the pharmacological actions of d-amphetamine, reserpine and alpha-methyltyrosine."}
{"id": "PMID:24731", "title": "Enhancement by choline of the induction of adrenal tyrosine hydroxylase by phenoxybenzamine, 6-hydroxydopamine, insulin or exposure to cold.", "content": "Treatments that increase the release of acetylcholine from the splanchnic nerve have previously been shown to induce the enzyme tyrosine hydroxylase in adrenal chromaffin cells. Such treatments include the systemic administration of the drugs phenoxybenzamine and 6-hydroxydopamine, insulin-induced hypoglycemia, and prolonged exposure to cold. We have reported that the administration of choline also induces the adrenal enzyme and have suggested that the mechanism of this induction involves an increase in the amount of acetylcholine released each time the splanchnic nerve fires. In the present studies, rats received both choline and one of the above treatments. Choline caused an augmentation of the adrenomedullary response to each of the treatments, but it had no apparent effect on a presynaptic enzyme, choline acetyltransferase. These observations strongly support the view that choline availability determines both the amount of acetylcholine present in nerve terminals and the amount liberated when cholinergic neurons fire.", "contents": "Enhancement by choline of the induction of adrenal tyrosine hydroxylase by phenoxybenzamine, 6-hydroxydopamine, insulin or exposure to cold. Treatments that increase the release of acetylcholine from the splanchnic nerve have previously been shown to induce the enzyme tyrosine hydroxylase in adrenal chromaffin cells. Such treatments include the systemic administration of the drugs phenoxybenzamine and 6-hydroxydopamine, insulin-induced hypoglycemia, and prolonged exposure to cold. We have reported that the administration of choline also induces the adrenal enzyme and have suggested that the mechanism of this induction involves an increase in the amount of acetylcholine released each time the splanchnic nerve fires. In the present studies, rats received both choline and one of the above treatments. Choline caused an augmentation of the adrenomedullary response to each of the treatments, but it had no apparent effect on a presynaptic enzyme, choline acetyltransferase. These observations strongly support the view that choline availability determines both the amount of acetylcholine present in nerve terminals and the amount liberated when cholinergic neurons fire."}
{"id": "PMID:24734", "title": "The increase in spontaneous transmitter release produced by beta-bungarotoxin and its modification by inorganic ions.", "content": "The excitatory phase of the biphasic action on transmitter release of the neurotoxin, beta-bungarotoxin (beta-BuTX; 0.5 microgram ml-1), was studied on miniature end-plate potentials (MEPPs) at frog sciatic nerve-sartorius muscle junctions. The most common type of excitatory response was characterized by a continuous increase in MEPP frequency that reached a plateau; a less common form was characterized by irregular episodic bursts of firing. There was a direct relationship between toxin activity and [K+]O (2.5-10.0 mM) with virtually no effect of the toxin at normal [K]O+ at the concentration of toxin used. In the absence of Mg++, there was a paradoxical inverse relationship between toxin activity and [Ca++]O (0.5-4.0 mM) at higher [K+]O. However, in the presence of 1.0 mM Mg++ the increased MEPP frequency produced by beta-BuTX was independent of [Ca++]O. The action of beta-BuTX was very sensitive to blockade by Mg++. Toxin activity was demonstrated in a Sr++-containing, Ca++-free solution, but not in a Mg++-containing, Ca++-free solution. It is probable that beta-BuTX causes a slight depolarization of the nerve terminals by a mechanism not sensitive to blockade by tetrodotoxin and that the ability of beta-BuTX to depolarize the terminals can account for the enhancement of the response by raising [K+]O and the depression of the response by Mg++. Alternatively, beta-BuTX could be producing its effects by some, as yet undefined, direct action on the release process.", "contents": "The increase in spontaneous transmitter release produced by beta-bungarotoxin and its modification by inorganic ions. The excitatory phase of the biphasic action on transmitter release of the neurotoxin, beta-bungarotoxin (beta-BuTX; 0.5 microgram ml-1), was studied on miniature end-plate potentials (MEPPs) at frog sciatic nerve-sartorius muscle junctions. The most common type of excitatory response was characterized by a continuous increase in MEPP frequency that reached a plateau; a less common form was characterized by irregular episodic bursts of firing. There was a direct relationship between toxin activity and [K+]O (2.5-10.0 mM) with virtually no effect of the toxin at normal [K]O+ at the concentration of toxin used. In the absence of Mg++, there was a paradoxical inverse relationship between toxin activity and [Ca++]O (0.5-4.0 mM) at higher [K+]O. However, in the presence of 1.0 mM Mg++ the increased MEPP frequency produced by beta-BuTX was independent of [Ca++]O. The action of beta-BuTX was very sensitive to blockade by Mg++. Toxin activity was demonstrated in a Sr++-containing, Ca++-free solution, but not in a Mg++-containing, Ca++-free solution. It is probable that beta-BuTX causes a slight depolarization of the nerve terminals by a mechanism not sensitive to blockade by tetrodotoxin and that the ability of beta-BuTX to depolarize the terminals can account for the enhancement of the response by raising [K+]O and the depression of the response by Mg++. Alternatively, beta-BuTX could be producing its effects by some, as yet undefined, direct action on the release process."}
{"id": "PMID:24735", "title": "The generation of nerve impulses in mammalian axons by changing the concentrations of the normal constituents of extracellular fluid.", "content": "1. Experiments have been performed to determine what changes in normal constituents of extracellular fluid are necessary to generate action potentials in mammalian axons. 2. Single and multifibre preparations of rat spinal roots were tested with Krebs solutions in which Na+, K+, Ca2+, Mg2+, pH, PCO2 or osmotic pressure were varied. 3. [Ca2+] below 1.0 mM produced impulses in all preparations. Lowering [Mg2+] did not generate any impulses but did enhance the response to low [Ca2+]. 4. Increasing [Na+] or [K+] caused excitation in some of the multifibres; increased [Na+] evoked 'off' responses in two single fibre preparations. The response to low [Ca2+] was enhanced by increasing [Na+] and depressed by increasing [K+]. 5. Increasing the osmotic pressure (with glucose) did not generate impulses and depressed the response to low [Ca2+]. 6. Changing the pH of Krebs solution did not generate impulses, but modified the response to other stimuli. The response to low [Ca2+] was increased as pH increased from pH 7.4 to 8.2, and decreased with pH in the range pH 7.4--6.2. 7. Altering pCO2 did not have any effect on the responses to low [Ca2+] unless pH also changed.", "contents": "The generation of nerve impulses in mammalian axons by changing the concentrations of the normal constituents of extracellular fluid. 1. Experiments have been performed to determine what changes in normal constituents of extracellular fluid are necessary to generate action potentials in mammalian axons. 2. Single and multifibre preparations of rat spinal roots were tested with Krebs solutions in which Na+, K+, Ca2+, Mg2+, pH, PCO2 or osmotic pressure were varied. 3. [Ca2+] below 1.0 mM produced impulses in all preparations. Lowering [Mg2+] did not generate any impulses but did enhance the response to low [Ca2+]. 4. Increasing [Na+] or [K+] caused excitation in some of the multifibres; increased [Na+] evoked 'off' responses in two single fibre preparations. The response to low [Ca2+] was enhanced by increasing [Na+] and depressed by increasing [K+]. 5. Increasing the osmotic pressure (with glucose) did not generate impulses and depressed the response to low [Ca2+]. 6. Changing the pH of Krebs solution did not generate impulses, but modified the response to other stimuli. The response to low [Ca2+] was increased as pH increased from pH 7.4 to 8.2, and decreased with pH in the range pH 7.4--6.2. 7. Altering pCO2 did not have any effect on the responses to low [Ca2+] unless pH also changed."}
{"id": "PMID:24736", "title": "Calcium and strontium concentration changes within skinned muscle preparations following a change in the external bathing solution.", "content": "1. A method for producing rapid [Ca2+] and [Sr2+] changes in the frog skinned muscle fibre preparation while maintaining constant all other cationic concentrations (Moisescu, 1976a, b) is described and analysed in detail. 2. Different experiments, some of them involving the Ca2+-sensitive photoprotein aequorin, as well as theoretical considerations, indicate that with this method one can produce a Ca2+ (or Sr2+) concentration change within 0.1--0.15 sec in a whole preparation having a diameter of 50 micrometer. 3. The rate of force development was similar to that observed in vivo. 4. The radial diffusion coefficient of EGTA in relaxed myofibrillar preparations was measured and found to be 4.6 x 10(-6) cm2sec-1 at 20 degrees C. 5. The sarcoplasmic reticulum in myofibrillar bundles was found to be active with respect to both Ca2+ and Sr2+ in the solutions used ([Mg2+] 1 mM; [Na] 30 mM; [K] 140-170 mM; [Cl] less than or equal to 20 mM; pH 7.10). 6. The amount of Ca released by caffeine from internal stores (previously loaded with Ca) can raise the total Ca concentration in the muscle fibre preparation by at least 1.8 mM. 7. The presence of 10 mM-caffeine in all bathing solutions reduced drastically the ability of the sarcoplasmic reticulum to accumulate both Ca and Sr.", "contents": "Calcium and strontium concentration changes within skinned muscle preparations following a change in the external bathing solution. 1. A method for producing rapid [Ca2+] and [Sr2+] changes in the frog skinned muscle fibre preparation while maintaining constant all other cationic concentrations (Moisescu, 1976a, b) is described and analysed in detail. 2. Different experiments, some of them involving the Ca2+-sensitive photoprotein aequorin, as well as theoretical considerations, indicate that with this method one can produce a Ca2+ (or Sr2+) concentration change within 0.1--0.15 sec in a whole preparation having a diameter of 50 micrometer. 3. The rate of force development was similar to that observed in vivo. 4. The radial diffusion coefficient of EGTA in relaxed myofibrillar preparations was measured and found to be 4.6 x 10(-6) cm2sec-1 at 20 degrees C. 5. The sarcoplasmic reticulum in myofibrillar bundles was found to be active with respect to both Ca2+ and Sr2+ in the solutions used ([Mg2+] 1 mM; [Na] 30 mM; [K] 140-170 mM; [Cl] less than or equal to 20 mM; pH 7.10). 6. The amount of Ca released by caffeine from internal stores (previously loaded with Ca) can raise the total Ca concentration in the muscle fibre preparation by at least 1.8 mM. 7. The presence of 10 mM-caffeine in all bathing solutions reduced drastically the ability of the sarcoplasmic reticulum to accumulate both Ca and Sr."}
{"id": "PMID:24737", "title": "The effect of external pH on osmotic permeability, ion and fluid transport across isolated frog skin.", "content": "1. The rate of volume flow across frog skin induced by an osmotic gradient was measured when normal (7.4) and low pH (2.28) solutions bathed the outside. The osmotic permeabilities (Pos) were 2.4 +/- 0.4 and 4.8 +/- 1.0 micrometer/sec, respectively. The change in Pos induced by low pH was reversible. 2. Volume flow in the absence of an osmotic gradient was measured at normal and low pH. Values were 0.69 +/- 0.13 and 1.1 +/- 0.2 microliter/hr. cm2, respectively; the paired differences were significant (P less than 0.0025). This change in rate was partially reversible upon return to normal pH. 3. The potential difference (V) and short-circuit current (Is) across skins were measured under several conditions and the following equivalent parameters in a simplified electrical model were computed: total resistance (Rt); shunt resistance (Rs); electromotive force of the pump (ENa); and salt transport at open circuit (JNaCl). Representative figures were (a), at pH 7.4: Is = 14 +/- 1.6 microampere/cm2; Rt = 3.3 +/- 0.4 komega.cm2; Rs = 7.2 +/- 1.0 komega.cm2; ENA = 103 +/- 38 mV; JNaCl = 7.2 +/- 1.2 microampere/cm2; (b) at pH 2.28: Is = 8.3 +/- 2.1 microampere/cm2; Rt = 0.46 +/- 0.12 komega. cm2; Rs = 0.65 +/- 0.06 komega.cm2; ENa = 59 +/- 25 mV; JNaCl = 9.4 +/- 3.3 microampere/cm2. 4. From the electrical parameters measured concomitantly with the rate of fluid transport in given experiments, the expected salt concentration of the transported fluid was 0.30 +/- 0.08 and 0.38 +/- 0.08 mole/l. at normal and low pH, respectively, or some 3-4 times hyperosmotic with respect to the medium. 5. Treatment with low pH on the outside has been found to open the intercellular junctions in previous studies. The present results suggest that, if such an effect occurs, it is localized only to a small fraction of the cell perimeter. Making certain assumptions that fraction could be as low as 0.003. 6. Low pH on the outside reversibly changes the electrical parameters of a 'tight' epithelium like the frog skin into values more typical of 'intermediate' epithelia; both the total and shunt resistances decrease to about 0.1 of their normal values. These changes do not apparently affect the osmolarity of the transported fluid.", "contents": "The effect of external pH on osmotic permeability, ion and fluid transport across isolated frog skin. 1. The rate of volume flow across frog skin induced by an osmotic gradient was measured when normal (7.4) and low pH (2.28) solutions bathed the outside. The osmotic permeabilities (Pos) were 2.4 +/- 0.4 and 4.8 +/- 1.0 micrometer/sec, respectively. The change in Pos induced by low pH was reversible. 2. Volume flow in the absence of an osmotic gradient was measured at normal and low pH. Values were 0.69 +/- 0.13 and 1.1 +/- 0.2 microliter/hr. cm2, respectively; the paired differences were significant (P less than 0.0025). This change in rate was partially reversible upon return to normal pH. 3. The potential difference (V) and short-circuit current (Is) across skins were measured under several conditions and the following equivalent parameters in a simplified electrical model were computed: total resistance (Rt); shunt resistance (Rs); electromotive force of the pump (ENa); and salt transport at open circuit (JNaCl). Representative figures were (a), at pH 7.4: Is = 14 +/- 1.6 microampere/cm2; Rt = 3.3 +/- 0.4 komega.cm2; Rs = 7.2 +/- 1.0 komega.cm2; ENA = 103 +/- 38 mV; JNaCl = 7.2 +/- 1.2 microampere/cm2; (b) at pH 2.28: Is = 8.3 +/- 2.1 microampere/cm2; Rt = 0.46 +/- 0.12 komega. cm2; Rs = 0.65 +/- 0.06 komega.cm2; ENa = 59 +/- 25 mV; JNaCl = 9.4 +/- 3.3 microampere/cm2. 4. From the electrical parameters measured concomitantly with the rate of fluid transport in given experiments, the expected salt concentration of the transported fluid was 0.30 +/- 0.08 and 0.38 +/- 0.08 mole/l. at normal and low pH, respectively, or some 3-4 times hyperosmotic with respect to the medium. 5. Treatment with low pH on the outside has been found to open the intercellular junctions in previous studies. The present results suggest that, if such an effect occurs, it is localized only to a small fraction of the cell perimeter. Making certain assumptions that fraction could be as low as 0.003. 6. Low pH on the outside reversibly changes the electrical parameters of a 'tight' epithelium like the frog skin into values more typical of 'intermediate' epithelia; both the total and shunt resistances decrease to about 0.1 of their normal values. These changes do not apparently affect the osmolarity of the transported fluid."}
{"id": "PMID:24738", "title": "Measurement of pH in the rat epididymis in vivo.", "content": "Antimony microelectrodes were used to measure pH in rat seminiferous tubules and epididymides in vivo. Acidification of fluid leaving the testis occurs primarily in the initial segment and to a lesser extent in the intermediate zone.", "contents": "Measurement of pH in the rat epididymis in vivo. Antimony microelectrodes were used to measure pH in rat seminiferous tubules and epididymides in vivo. Acidification of fluid leaving the testis occurs primarily in the initial segment and to a lesser extent in the intermediate zone."}
{"id": "PMID:24748", "title": "Chloride conductance of the amphiuma red cell membrane.", "content": "Like most other red cells, the giant erythrocytes of Amphiuma means possess a system for rapid exchange of chloride across the membrane. Also, there are indications that the net transport of chloride in these cells is slow. The size of Amphiuma erythrocytes allows direct measurements of membrane potential with microelectrodes. The present work exploits the possibility that such measurements can be used to give a quantitative estimate of the chloride conductance (GCl) of the Amphiuma red cell membrane. The membrane potential was measured as a function of extracellular chloride concentration (5-120mM), using an impermeant anion (Para-amino-hippurate) as a substitute. Furthermore, the effect of different pH values (6.0-7.2) was studied. For each extracellular chloride concentration the membrane potential was determined at a pH at which hydroxyl, hydrogen, and bicarbonate ions were in electrochemical equilibrium. From these membrane potentials and the corresponding chloride concentrations in the medium (at constant intracellular ion concentrations), the GCl of the membrane was calculated to be 3.9 x 10-7 omega-1 cm-2. This value is some six orders of magnitude smaller than that calculated from the rate of tracer exchange under equilibrium conditions. The experimental strategy used gives the values for a \"partial transference number\" which takes into account only ions which are not in electrochemical equilibrium. Whereas this approach gives a value for GCl, it does not permit calculation of the overall membrane conductance. From the calculated value of GCl it is possible to estimate that the maximal value of the combined conductances of hydroxyl (or proton) and bicarbonate ions is 0.6 x 10-7 omega-1 cm-2. The large discrepancy between the rate of exchange of chloride and its conductance is in agreement with measurements on human and sheep red cells employing the ionophore valinomycin to increase the potassium conductance of the membrane. The results in the present study were, however, obtained without valinomycin and an accompaning assumption of a constant field in the membrane. Therefore, the present measurements give independent support to the above mentioned conclusions.", "contents": "Chloride conductance of the amphiuma red cell membrane. Like most other red cells, the giant erythrocytes of Amphiuma means possess a system for rapid exchange of chloride across the membrane. Also, there are indications that the net transport of chloride in these cells is slow. The size of Amphiuma erythrocytes allows direct measurements of membrane potential with microelectrodes. The present work exploits the possibility that such measurements can be used to give a quantitative estimate of the chloride conductance (GCl) of the Amphiuma red cell membrane. The membrane potential was measured as a function of extracellular chloride concentration (5-120mM), using an impermeant anion (Para-amino-hippurate) as a substitute. Furthermore, the effect of different pH values (6.0-7.2) was studied. For each extracellular chloride concentration the membrane potential was determined at a pH at which hydroxyl, hydrogen, and bicarbonate ions were in electrochemical equilibrium. From these membrane potentials and the corresponding chloride concentrations in the medium (at constant intracellular ion concentrations), the GCl of the membrane was calculated to be 3.9 x 10-7 omega-1 cm-2. This value is some six orders of magnitude smaller than that calculated from the rate of tracer exchange under equilibrium conditions. The experimental strategy used gives the values for a \"partial transference number\" which takes into account only ions which are not in electrochemical equilibrium. Whereas this approach gives a value for GCl, it does not permit calculation of the overall membrane conductance. From the calculated value of GCl it is possible to estimate that the maximal value of the combined conductances of hydroxyl (or proton) and bicarbonate ions is 0.6 x 10-7 omega-1 cm-2. The large discrepancy between the rate of exchange of chloride and its conductance is in agreement with measurements on human and sheep red cells employing the ionophore valinomycin to increase the potassium conductance of the membrane. The results in the present study were, however, obtained without valinomycin and an accompaning assumption of a constant field in the membrane. Therefore, the present measurements give independent support to the above mentioned conclusions."}
{"id": "PMID:24754", "title": "Resistance to Marek's disease. Effect of Corynebacterium parvum and Marek's tumor cell vaccines on tumorigenesis in chickens.", "content": "A study of nonspecific stimulation of the avian immune system with Corynebacterium parvum and specific stimulation with Marek's tumor cell vaccines revealed that nonspecifically stimulated outbred White Leghorn-type cockerels had higher incidences of tumors than did controls. A study of tumor cell cytotoxicity of sera from Marek's disease virus exposed birds indicated that humoral factors may play some role in tumor resistance.", "contents": "Resistance to Marek's disease. Effect of Corynebacterium parvum and Marek's tumor cell vaccines on tumorigenesis in chickens. A study of nonspecific stimulation of the avian immune system with Corynebacterium parvum and specific stimulation with Marek's tumor cell vaccines revealed that nonspecifically stimulated outbred White Leghorn-type cockerels had higher incidences of tumors than did controls. A study of tumor cell cytotoxicity of sera from Marek's disease virus exposed birds indicated that humoral factors may play some role in tumor resistance."}
{"id": "PMID:24755", "title": "Traumatic pseudoaneurysm of the dorsalis pedis artery in a child.", "content": "A basic principle of children's surgery is to plan it to last for 70 years. The successful reconstruction of the dorsalis pedis artery in an 8-year-old after trauma may be of benefit if he develops peripheral vascular disease as an adult.", "contents": "Traumatic pseudoaneurysm of the dorsalis pedis artery in a child. A basic principle of children's surgery is to plan it to last for 70 years. The successful reconstruction of the dorsalis pedis artery in an 8-year-old after trauma may be of benefit if he develops peripheral vascular disease as an adult."}
{"id": "PMID:24756", "title": "Multiple endocrine adenomatosis: in support of the common origin theories.", "content": "Herein we give clinical support to the theory of a common origin of multiple endocrine adenomatosis. Accurate clinical evaluation of a patient suspected to have endocrine neoplasia requires the search for a much wider range of potential endocrine tumors. Such an approach is now made possible by the radioimmunoassay. Chromosome patterns and histocompatibility antigens are reviewed in a family with the disease.", "contents": "Multiple endocrine adenomatosis: in support of the common origin theories. Herein we give clinical support to the theory of a common origin of multiple endocrine adenomatosis. Accurate clinical evaluation of a patient suspected to have endocrine neoplasia requires the search for a much wider range of potential endocrine tumors. Such an approach is now made possible by the radioimmunoassay. Chromosome patterns and histocompatibility antigens are reviewed in a family with the disease."}
{"id": "PMID:24757", "title": "Anxiety states in general practice.", "content": "Anxiety is commonly encountered in patient seen by the general practitioner. Frequently it either stimulates an organic condition involving one or more systems of the body or may aggravate symptoms of already existent organic pathology. Presence of environmental stresses and of personal conflicts in the life history of patient and the absence of physical findings on physical examination should alert the physician of this condition. Pharmacotherapy with minor tranquilizers and reassurance generally produce amelioration of symptoms.", "contents": "Anxiety states in general practice. Anxiety is commonly encountered in patient seen by the general practitioner. Frequently it either stimulates an organic condition involving one or more systems of the body or may aggravate symptoms of already existent organic pathology. Presence of environmental stresses and of personal conflicts in the life history of patient and the absence of physical findings on physical examination should alert the physician of this condition. Pharmacotherapy with minor tranquilizers and reassurance generally produce amelioration of symptoms."}
{"id": "PMID:24770", "title": "Laboratory and field assessment of the molluscicidal activity of gogo (Entada phaseoloides) against the amphibious snail intermediate host of Schistosoma japonicum.", "content": "A molluscicidal fraction occurs naturally in the bark of a vine (gogo in Tagalog), Entada phaseoloides, which grows indigeneously and abundantly in the Philippines. Butanol fraction of the methanol extracts of the bark was most toxic against Oncomelania quadrasi with the LC50 of 3.6-5.8 ppm. Analytical work on the butanol fraction by thin layer chromatography indicated that the active molluscicidal agents contained at least two kinds of saponins. The potency of E. phaseoloides remained rather stable over a wide range of pH values, in the presence of minerals and yeast cells and after ultraviolet irradiation of solutions. Our preliminary field trials, however, showed that doses as higher than 40 g per square meter would be needed to produce a satisfactory molluscicidal effect under field conditions.", "contents": "Laboratory and field assessment of the molluscicidal activity of gogo (Entada phaseoloides) against the amphibious snail intermediate host of Schistosoma japonicum. A molluscicidal fraction occurs naturally in the bark of a vine (gogo in Tagalog), Entada phaseoloides, which grows indigeneously and abundantly in the Philippines. Butanol fraction of the methanol extracts of the bark was most toxic against Oncomelania quadrasi with the LC50 of 3.6-5.8 ppm. Analytical work on the butanol fraction by thin layer chromatography indicated that the active molluscicidal agents contained at least two kinds of saponins. The potency of E. phaseoloides remained rather stable over a wide range of pH values, in the presence of minerals and yeast cells and after ultraviolet irradiation of solutions. Our preliminary field trials, however, showed that doses as higher than 40 g per square meter would be needed to produce a satisfactory molluscicidal effect under field conditions."}
{"id": "PMID:24776", "title": "Pharmacology of Sch 11973, N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea, a potential new antianginal agent.", "content": "Antianginal drugs were evaluated on the basis of their ability to protect against subepicardial electrogram changes induced by local ventricular ischemia in anesthetized dogs. Sch 11973 [N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea], a potential new antianginal agent, was also effective against local ventricular ischemia with its maximum effect appearing at 1mg/kg, i.v. or i.d. and with a duration of at least 2 hours. Nitroglycerin, at a dose of 0.04 mg/kg given bucally, exerted less protection, lasting on the average less than 15 minutes. Protection by propranolol at 1 mg/kg, i.v., was not better than nitroglycerin, but lasted up to one hour, while dipyridamole was ineffective when given in a dose range of 0.1-10 mg/kg, i.v. Sch 11973 differed from standard antianginal agents which may act via beta-adrenergic blocking activity or alteration of cardiac or circulatory dynamics since no acute pharmacological changes were observed after Sch 11973 was administered.", "contents": "Pharmacology of Sch 11973, N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea, a potential new antianginal agent. Antianginal drugs were evaluated on the basis of their ability to protect against subepicardial electrogram changes induced by local ventricular ischemia in anesthetized dogs. Sch 11973 [N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea], a potential new antianginal agent, was also effective against local ventricular ischemia with its maximum effect appearing at 1mg/kg, i.v. or i.d. and with a duration of at least 2 hours. Nitroglycerin, at a dose of 0.04 mg/kg given bucally, exerted less protection, lasting on the average less than 15 minutes. Protection by propranolol at 1 mg/kg, i.v., was not better than nitroglycerin, but lasted up to one hour, while dipyridamole was ineffective when given in a dose range of 0.1-10 mg/kg, i.v. Sch 11973 differed from standard antianginal agents which may act via beta-adrenergic blocking activity or alteration of cardiac or circulatory dynamics since no acute pharmacological changes were observed after Sch 11973 was administered."}
{"id": "PMID:24777", "title": "Involvement of histamine H1- and H2-receptors in induced asthmas in dogs.", "content": "Participation of histamine H1- and H2-receptors in both asthmas, i.e. experimentally induced bronchoconstriction and bronchosecretion, with ascaris suum and histamine in anesthetized dogs was investigated. Dogs given 0.2% histamine solution or ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5-5.0 fold. Airway secretion volume was also significantly increased 3-4 fold. The increase in Rrs by histamine inhalation was effectively inhibited or abolished by a histamine H1-receptor antagonist, chlorpheniramine (0.3-1 mg/kg i.v.), but not by a H2-receptor antagonist, cimetidine (1-3 mg/kg i.v.). The increase in Rrs by antigen inhalation was reduced by relatively high doses of chlorpheniramine (1-3 mg/kg i.v.), and not by cimetidine. In contrast, hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by either chlorpheniramine or cimetidine. Combinations of both antagonists abolished the hypersecretion. Atropine (2 mg/kg i.v.) significantly inhibited the occurrence of responses in both asthmas. The results suggest that histamine is involved in the allergic asthma produced by ascaris suum and that histamine directly evokes airway constriction through H1-receptors and hypersecretion of tracheobronchial fluid through H1- and H2-receptors, and, in part, indirectly activates the cholinergic pathway.", "contents": "Involvement of histamine H1- and H2-receptors in induced asthmas in dogs. Participation of histamine H1- and H2-receptors in both asthmas, i.e. experimentally induced bronchoconstriction and bronchosecretion, with ascaris suum and histamine in anesthetized dogs was investigated. Dogs given 0.2% histamine solution or ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5-5.0 fold. Airway secretion volume was also significantly increased 3-4 fold. The increase in Rrs by histamine inhalation was effectively inhibited or abolished by a histamine H1-receptor antagonist, chlorpheniramine (0.3-1 mg/kg i.v.), but not by a H2-receptor antagonist, cimetidine (1-3 mg/kg i.v.). The increase in Rrs by antigen inhalation was reduced by relatively high doses of chlorpheniramine (1-3 mg/kg i.v.), and not by cimetidine. In contrast, hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by either chlorpheniramine or cimetidine. Combinations of both antagonists abolished the hypersecretion. Atropine (2 mg/kg i.v.) significantly inhibited the occurrence of responses in both asthmas. The results suggest that histamine is involved in the allergic asthma produced by ascaris suum and that histamine directly evokes airway constriction through H1-receptors and hypersecretion of tracheobronchial fluid through H1- and H2-receptors, and, in part, indirectly activates the cholinergic pathway."}
{"id": "PMID:24778", "title": "The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. I. The relationship between contracture and respiration.", "content": "Papaverine (Pap) inhibited a tonic tension development in guinea pig taenia coli induced by an elevation of the potassium concentration of the medium to 40 mM (40-K). The ID50 of Pap was 4.5 x 10(-6) M. Inhibition of the 40-K induced tonic tension by Pap was dependent on the calculated concentration of non-ionized form, but not the ionized form. Inhibition of the tonic tension by Pap and various metabolic inhibitors was not antagonized by raising the Ca++ concentration in the medium. Results obtained from simultaneous measurement of the 40-K induced O2 consumption and tension illustrated that the inhibition of O2 consumption rapidly induced the inhibition of the tension. Furthermore, glucose removal, amytal or Pap resulted in a progressive relationship between the inhibition of O2 consumption and the inhibition of tension. The inhibition of Pap as determined by O2 consumption was not reversed by application of 10(-4) M 2,4-dinitrophenol (DNP). These results plus graphical analysis of the mechanical response suggest that Pap may penetrate the cell membrane and inhibit mitochondrial respiration, thereby inhibiting this very respiration-dependent contracture.", "contents": "The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. I. The relationship between contracture and respiration. Papaverine (Pap) inhibited a tonic tension development in guinea pig taenia coli induced by an elevation of the potassium concentration of the medium to 40 mM (40-K). The ID50 of Pap was 4.5 x 10(-6) M. Inhibition of the 40-K induced tonic tension by Pap was dependent on the calculated concentration of non-ionized form, but not the ionized form. Inhibition of the tonic tension by Pap and various metabolic inhibitors was not antagonized by raising the Ca++ concentration in the medium. Results obtained from simultaneous measurement of the 40-K induced O2 consumption and tension illustrated that the inhibition of O2 consumption rapidly induced the inhibition of the tension. Furthermore, glucose removal, amytal or Pap resulted in a progressive relationship between the inhibition of O2 consumption and the inhibition of tension. The inhibition of Pap as determined by O2 consumption was not reversed by application of 10(-4) M 2,4-dinitrophenol (DNP). These results plus graphical analysis of the mechanical response suggest that Pap may penetrate the cell membrane and inhibit mitochondrial respiration, thereby inhibiting this very respiration-dependent contracture."}
{"id": "PMID:24782", "title": "Intraoperative measurement of lower esophageal spincter pressure.", "content": "The lower esophageal sphincter pressure has been measured intraoperatively in 200 patients with gastroesophageal reflux and in three patients with achalasia. Lower esophageal sphincter pressure is measured before and during repair. Calibrating the cardia during performance of the median arcuate posterior gastropexy allows a sphincter pressure between 50 and 57 mm. Hg to be obtained at operation. The postoperative pressures have ranged between 15 and 25 mm. Hg, or approximately half of the intraoperative pressure. No patient with a spincter pressure of 15 mm. Hg or greater has reflux according to postoperative pH and pressure studies. Correction of reflux correlates well with relief of symptoms. Three patients with achalasia had intraoperative manometrics during myotomy. The lower esophageal sphincter pressure was lowered and the length of the lower esophageal sphincter was shortened. Dysphagia was corrected without producing reflux. This is the first report of measurement of lower esophageal sphincter pressure in anesthetized patients. Intraoperative measurement of sphincter pressure is a safe, simple, and reliable technique which allows the surgeon, for the first time, to determine the status of the lower esophageal sphincter during the operation. This technique should be standard for all operations on the gastroesophageal junction.", "contents": "Intraoperative measurement of lower esophageal spincter pressure. The lower esophageal sphincter pressure has been measured intraoperatively in 200 patients with gastroesophageal reflux and in three patients with achalasia. Lower esophageal sphincter pressure is measured before and during repair. Calibrating the cardia during performance of the median arcuate posterior gastropexy allows a sphincter pressure between 50 and 57 mm. Hg to be obtained at operation. The postoperative pressures have ranged between 15 and 25 mm. Hg, or approximately half of the intraoperative pressure. No patient with a spincter pressure of 15 mm. Hg or greater has reflux according to postoperative pH and pressure studies. Correction of reflux correlates well with relief of symptoms. Three patients with achalasia had intraoperative manometrics during myotomy. The lower esophageal sphincter pressure was lowered and the length of the lower esophageal sphincter was shortened. Dysphagia was corrected without producing reflux. This is the first report of measurement of lower esophageal sphincter pressure in anesthetized patients. Intraoperative measurement of sphincter pressure is a safe, simple, and reliable technique which allows the surgeon, for the first time, to determine the status of the lower esophageal sphincter during the operation. This technique should be standard for all operations on the gastroesophageal junction."}
{"id": "PMID:24784", "title": "The mechanism and control of human erythrocyte zinc uptake.", "content": "The increasing awareness of the importance of the divalent cation zinc in normal and pathologic cell functions has prompted our investigations into the mechanism and control of human erythrocyte zinc uptake. The albumin in blood plasma appears to be the main zinc binding moiety, effectively limiting zinc availability ot the red cell. In non-protein and non-phosphate-containing buffers (i.e., bicarbonate or Tris buffer) red cells sequester more than 90% of the extracellular zinc within 10--15 minutes at a rate more than 250 times faster than zink uptake by cells in plasma. In an albumin-containing media, the influx on red blood cell zinc is lightly temperature sensitive (decreased) between 37 degrees C and 25 degrees C, whereas with cells in bicarbonate buffer alone temperature sensitivity does not begin until below 25 degrees C. Over the physiological range, pH variation has a minimal effect on zinc uptake regardless of the media employed. Finally, once associated with the red cell zinc tends to remain, with a zinc efflux less than 2% of influx. We conclude that human erythrocytes are highly permeable to zinc, with the rate and amount of zinc taken up controlled primarily by the zinc binding characteristics of the media in which the cells are suspended.", "contents": "The mechanism and control of human erythrocyte zinc uptake. The increasing awareness of the importance of the divalent cation zinc in normal and pathologic cell functions has prompted our investigations into the mechanism and control of human erythrocyte zinc uptake. The albumin in blood plasma appears to be the main zinc binding moiety, effectively limiting zinc availability ot the red cell. In non-protein and non-phosphate-containing buffers (i.e., bicarbonate or Tris buffer) red cells sequester more than 90% of the extracellular zinc within 10--15 minutes at a rate more than 250 times faster than zink uptake by cells in plasma. In an albumin-containing media, the influx on red blood cell zinc is lightly temperature sensitive (decreased) between 37 degrees C and 25 degrees C, whereas with cells in bicarbonate buffer alone temperature sensitivity does not begin until below 25 degrees C. Over the physiological range, pH variation has a minimal effect on zinc uptake regardless of the media employed. Finally, once associated with the red cell zinc tends to remain, with a zinc efflux less than 2% of influx. We conclude that human erythrocytes are highly permeable to zinc, with the rate and amount of zinc taken up controlled primarily by the zinc binding characteristics of the media in which the cells are suspended."}
{"id": "PMID:24785", "title": "Determinants of lengths of outpatient visits in a prepaid group practice setting.", "content": "In this paper we have examined the amount of time that physicians (MDs) and physician's assistants (PAs) expended on office visits. The purpose was to determine the extent to which a series of patient-related and system-related characteristics explain variations in that time. Using regression analyses, we found most of the explained variation generally to be due to system-related characteristics. Whether the provider was an MD or PA made little difference in the length of time spent with patients. The principal determinant of provider time for unscheduled and scheduled 15-minute visits was the patient-load (number of patients per minute); for scheduled 30-minute visits, the number of associated morbidities was relatively more important than patient-load. Discriminant analysis was used to identify factors that could distinguish PA visits that require an MD input from those that do not. The data were collected from three months of observation in the department of medicine of a prepaid group practice.", "contents": "Determinants of lengths of outpatient visits in a prepaid group practice setting. In this paper we have examined the amount of time that physicians (MDs) and physician's assistants (PAs) expended on office visits. The purpose was to determine the extent to which a series of patient-related and system-related characteristics explain variations in that time. Using regression analyses, we found most of the explained variation generally to be due to system-related characteristics. Whether the provider was an MD or PA made little difference in the length of time spent with patients. The principal determinant of provider time for unscheduled and scheduled 15-minute visits was the patient-load (number of patients per minute); for scheduled 30-minute visits, the number of associated morbidities was relatively more important than patient-load. Discriminant analysis was used to identify factors that could distinguish PA visits that require an MD input from those that do not. The data were collected from three months of observation in the department of medicine of a prepaid group practice."}
{"id": "PMID:24797", "title": "Transport of 14C-L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus in axenic culture.", "content": "Transport of L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus grown in axenic culture was investigated using endogenously metabolizing cells. Transport occurred against a concentration gradient and required the expenditure of energy supplied by metabolic reactions that were inhibited by catalytic amounts of sodium azide and 2,4-dinitrophenol. The process exhibited both pH and temperature dependence with optima at pH 4 and 35 degrees C, respectively. The energy of activation and Q10 for transport were calculated to be 18,227 cal/mole and 2.82 respectively, between 20 and 30 degrees C. The kinetics of the system were consistent with a mechanism of transport that depended upon a finite number of sites on the cell surface and had a Kt of 1.46 x 10(-5) M. The system for L-glycine transport lacked sterospecificity and was most inhibited in the presence of other neutral amino acids while less inhibition was observed in the presence of the acidic and basic amino acids. These results suggest that L-glycine transport in this mycoparasite occurs by an energy dependent, protein-mediated process characteristic of active transport.", "contents": "Transport of 14C-L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus in axenic culture. Transport of L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus grown in axenic culture was investigated using endogenously metabolizing cells. Transport occurred against a concentration gradient and required the expenditure of energy supplied by metabolic reactions that were inhibited by catalytic amounts of sodium azide and 2,4-dinitrophenol. The process exhibited both pH and temperature dependence with optima at pH 4 and 35 degrees C, respectively. The energy of activation and Q10 for transport were calculated to be 18,227 cal/mole and 2.82 respectively, between 20 and 30 degrees C. The kinetics of the system were consistent with a mechanism of transport that depended upon a finite number of sites on the cell surface and had a Kt of 1.46 x 10(-5) M. The system for L-glycine transport lacked sterospecificity and was most inhibited in the presence of other neutral amino acids while less inhibition was observed in the presence of the acidic and basic amino acids. These results suggest that L-glycine transport in this mycoparasite occurs by an energy dependent, protein-mediated process characteristic of active transport."}
{"id": "PMID:24798", "title": "New approaches to the pathogenesis of peptic ulcer based on the protective action of saliva with special reference to roughage, vegetable fibre and fermented milk products.", "content": "Epidemiologic studies have shown differences in the prevalence of peptic ulcer disease among various communities to be related to variation in diet and eating patterns. Results of studies of the effect of diet and pattern of eating on saliva, on gastric juice, and on the amount of bile are reviewed. It is suggested that bile, and not hydrochloric acid, plays the causative role in pathogenesis of peptic ulceration. The role of saliva in the prevention of peptic ulcer is emphasized. The salivary mucus swallowed with food is protective because it decreases the flow rate of bile which, when held in the gall bladder longer, loses its alkalinity and therefore its ability to damage the mucous cells. Roughage, cellulose and vegetable fibres and fermented milk products act in a similar manner. When food is well masticated, containing plenty of vegetable fibres and fermented milk products such as ghee and yoghurt, resulting in an increase in the amount of salivary mucus, peptic ulceration may be prevented and cured and relapses may be prevented. This does not require a big change in the pattern of diet but only a change in the manner of eating so that hasty eating is avoided and good is chewed well. The pattern of diet, especially the relative dietary preponderance of short-chain fatty acids, such as those present in milk, yoghurt and other fermented milk products, have a protective action; the short-chain fatty acids retard gall bladder contraction and thus diminish the amount of bile entering the duodenal lumen.", "contents": "New approaches to the pathogenesis of peptic ulcer based on the protective action of saliva with special reference to roughage, vegetable fibre and fermented milk products. Epidemiologic studies have shown differences in the prevalence of peptic ulcer disease among various communities to be related to variation in diet and eating patterns. Results of studies of the effect of diet and pattern of eating on saliva, on gastric juice, and on the amount of bile are reviewed. It is suggested that bile, and not hydrochloric acid, plays the causative role in pathogenesis of peptic ulceration. The role of saliva in the prevention of peptic ulcer is emphasized. The salivary mucus swallowed with food is protective because it decreases the flow rate of bile which, when held in the gall bladder longer, loses its alkalinity and therefore its ability to damage the mucous cells. Roughage, cellulose and vegetable fibres and fermented milk products act in a similar manner. When food is well masticated, containing plenty of vegetable fibres and fermented milk products such as ghee and yoghurt, resulting in an increase in the amount of salivary mucus, peptic ulceration may be prevented and cured and relapses may be prevented. This does not require a big change in the pattern of diet but only a change in the manner of eating so that hasty eating is avoided and good is chewed well. The pattern of diet, especially the relative dietary preponderance of short-chain fatty acids, such as those present in milk, yoghurt and other fermented milk products, have a protective action; the short-chain fatty acids retard gall bladder contraction and thus diminish the amount of bile entering the duodenal lumen."}
{"id": "PMID:24802", "title": "[Inhibition of electron transport and photophosphorylation in chloroplasts by quercetin].", "content": "The influence of quercetin on electron transport and photophosphorylation of pea isolated chloroplasts with methylviologen and NADP+ has been studied. Quercetin inhibits ATP synthesis and phosphorylating electron transport but does not affect the basal electron transport in the presence of methylviologen. In view of these data and because of the increase of the proton uptake by chloroplasts in the presence of quercetin we consider it as an inhibitor of energy transfer. Under conditions of NADP+ photoreduction quercetin acts also as an inhibitor of electron transfer, interacting with ferredoxin, though a complete inhibition of electron transfer has not been observed. This last phenomenon may be of importance for the understanding of the detailed mechanism of NADP+ reduction by chloroplasts.", "contents": "[Inhibition of electron transport and photophosphorylation in chloroplasts by quercetin]. The influence of quercetin on electron transport and photophosphorylation of pea isolated chloroplasts with methylviologen and NADP+ has been studied. Quercetin inhibits ATP synthesis and phosphorylating electron transport but does not affect the basal electron transport in the presence of methylviologen. In view of these data and because of the increase of the proton uptake by chloroplasts in the presence of quercetin we consider it as an inhibitor of energy transfer. Under conditions of NADP+ photoreduction quercetin acts also as an inhibitor of electron transfer, interacting with ferredoxin, though a complete inhibition of electron transfer has not been observed. This last phenomenon may be of importance for the understanding of the detailed mechanism of NADP+ reduction by chloroplasts."}
{"id": "PMID:24803", "title": "[Equilibrium dynamics of the 3-dimensional structure of globular proteins].", "content": "According to the data of many physical and physico-chemical methods for conditions near to physiological, there are two types of spontaneous reversible conformational transitions in native proteins namely, local transconformations and overall unfolding of the molecule. Conformational transitions of both types occur with correlation times of less than 10-1--10-3 sec. Some local transconformations, especially those revealed by the hydrogen exchange method, are characterized by weak temperature dependence of the equilibrium constant (local temperature-independent (TI) transconformations). Combining the data obtained by the hydrogen exchange method with recently published results of energy refinement of protein structure leads us to suggest that the probability of local TI-transconformations is independent of hydrophobic forces and possibly related to the \"internal\" conformational free energy of the native protein, i.e. the sum of (1) the potentional energy of non-bonded intramolecular interactions, (2) the energy of dihedral and bond angle strain as well as (3) the entropy of the folded protein. In the proposed model of dynamic structure the cooperative nature of local TI-transconformations is a result of close interrelation between the optimization of van der Waals side chain interactions in the nonpolar core and variation of dihedral and valence angles. It is shown that the local TI-conformers are closely related to the functionally important transient key states of native proteins.", "contents": "[Equilibrium dynamics of the 3-dimensional structure of globular proteins]. According to the data of many physical and physico-chemical methods for conditions near to physiological, there are two types of spontaneous reversible conformational transitions in native proteins namely, local transconformations and overall unfolding of the molecule. Conformational transitions of both types occur with correlation times of less than 10-1--10-3 sec. Some local transconformations, especially those revealed by the hydrogen exchange method, are characterized by weak temperature dependence of the equilibrium constant (local temperature-independent (TI) transconformations). Combining the data obtained by the hydrogen exchange method with recently published results of energy refinement of protein structure leads us to suggest that the probability of local TI-transconformations is independent of hydrophobic forces and possibly related to the \"internal\" conformational free energy of the native protein, i.e. the sum of (1) the potentional energy of non-bonded intramolecular interactions, (2) the energy of dihedral and bond angle strain as well as (3) the entropy of the folded protein. In the proposed model of dynamic structure the cooperative nature of local TI-transconformations is a result of close interrelation between the optimization of van der Waals side chain interactions in the nonpolar core and variation of dihedral and valence angles. It is shown that the local TI-conformers are closely related to the functionally important transient key states of native proteins."}
{"id": "PMID:24804", "title": "[Stationary kinetics of catalysis by the hydrogenase of Thiocapsa roseopersicina].", "content": "Forward and reverse reactions of catalysis by a hydrogenase from T. roseopersicina in steady state have been investigated. The dependance of reaction rate on the concentration of substrates and of hydrogen ions has been studied. Detailed formal-kinetic analysis of possible mechanisms of enzyme action has been carried out and the classification of mechanisms of the reaction has been given. Comparison of experimental data with the equations obtained from formal-kinetic analysis has been undertaken and mechanisms compatible with experimental data were sorted out. Kinetic and molecular mechanism of the catalytic activity of hydrogenase has been proposed and elementary rate constants for the activation of molecular hydrogen have been calculated.", "contents": "[Stationary kinetics of catalysis by the hydrogenase of Thiocapsa roseopersicina]. Forward and reverse reactions of catalysis by a hydrogenase from T. roseopersicina in steady state have been investigated. The dependance of reaction rate on the concentration of substrates and of hydrogen ions has been studied. Detailed formal-kinetic analysis of possible mechanisms of enzyme action has been carried out and the classification of mechanisms of the reaction has been given. Comparison of experimental data with the equations obtained from formal-kinetic analysis has been undertaken and mechanisms compatible with experimental data were sorted out. Kinetic and molecular mechanism of the catalytic activity of hydrogenase has been proposed and elementary rate constants for the activation of molecular hydrogen have been calculated."}
{"id": "PMID:24808", "title": "Effect of hypnotic and anxiolytic agents on regional concentration of acetylcholine in rat brain.", "content": "Pentobarbital (30 and 60 mg/kg) and chloral hydrate (300 and 600 mg/kg) administered in anesthetic/hypnotic doses produced significant increases in acetylcholine concentration in the cerebral cortex, striatum, hippocampus and brainstem. Hypnotic/anxiolytic agents like diazepam, flurazepam (100 mg/kg each) and triazolam (30 mg/kg) significantly increased the acetylcholine concentration only in the cerebral cortex and striatum. Alprazolam and ketazolam had no significant effect on regional distribution of acetylcholine in the brain. The results have been discussed with respect to the role of central cholinergic system in anesthetic and hypnotic actions of these drugs.", "contents": "Effect of hypnotic and anxiolytic agents on regional concentration of acetylcholine in rat brain. Pentobarbital (30 and 60 mg/kg) and chloral hydrate (300 and 600 mg/kg) administered in anesthetic/hypnotic doses produced significant increases in acetylcholine concentration in the cerebral cortex, striatum, hippocampus and brainstem. Hypnotic/anxiolytic agents like diazepam, flurazepam (100 mg/kg each) and triazolam (30 mg/kg) significantly increased the acetylcholine concentration only in the cerebral cortex and striatum. Alprazolam and ketazolam had no significant effect on regional distribution of acetylcholine in the brain. The results have been discussed with respect to the role of central cholinergic system in anesthetic and hypnotic actions of these drugs."}
{"id": "PMID:24814", "title": "Effect of estrogen and progesterone on the release of MSH in gonadectomized rats.", "content": "The concentration of MSH in serum after estrogen or progesterone injection into gonadectomized rats was measured by a biological assay. Undetectable serum MSH values were found in long-term ovariectomized (OVX) rats. After a single injection of 10 microgram estradiol benzoate (EB) serum MSH exhibited a circadiam rhythm with high levels in the afternoon, while values in the morning were negative. This effect occurred for 4 days following the injection. Progesterone injection into spayed rats also resulted in an increase of serum MSH concentration, but in contrast to the changes observed after EB treatment high values were found in the morning for 3 consecutive days. Afternoon MSH levels were low but measurable. The effect of these steroids on the activity of the hypothalamic enzymes which yielded MIF or MRF upon incubation with oxytocin (OXT) was also studied. Enzymatic activity of both systems was undetectable in OVX rats and was evident after EB treatment. Progesterone increased only the activity of the system which yields MRF. In castrated male rats estrogen elevated baseline MSH levels but a circadian rhythm was not observed, whereas progesterone had no effect. These observations demonstrate a sex difference on steroid-induced MSH release.", "contents": "Effect of estrogen and progesterone on the release of MSH in gonadectomized rats. The concentration of MSH in serum after estrogen or progesterone injection into gonadectomized rats was measured by a biological assay. Undetectable serum MSH values were found in long-term ovariectomized (OVX) rats. After a single injection of 10 microgram estradiol benzoate (EB) serum MSH exhibited a circadiam rhythm with high levels in the afternoon, while values in the morning were negative. This effect occurred for 4 days following the injection. Progesterone injection into spayed rats also resulted in an increase of serum MSH concentration, but in contrast to the changes observed after EB treatment high values were found in the morning for 3 consecutive days. Afternoon MSH levels were low but measurable. The effect of these steroids on the activity of the hypothalamic enzymes which yielded MIF or MRF upon incubation with oxytocin (OXT) was also studied. Enzymatic activity of both systems was undetectable in OVX rats and was evident after EB treatment. Progesterone increased only the activity of the system which yields MRF. In castrated male rats estrogen elevated baseline MSH levels but a circadian rhythm was not observed, whereas progesterone had no effect. These observations demonstrate a sex difference on steroid-induced MSH release."}
{"id": "PMID:24815", "title": "Prolactin inhibiting activity of dopamine-free subcellular fractions from rat mediobasal hypothalamus.", "content": "In order to check the hypothesis of an identity of dopamine (DA) and prolactin inhibiting activity (PIF), their subcellular distribution was studied in the mediobasal hypothalamus (MBH) and the striatum, which served as a control structure. PIF was tested both in vivo and on pituitary incubates. Fractions were also assayed after adsorption of their catecholamine content on alumina, as well as in presence of haloperidol or alpha-flupentixol, potent DA receptor inhibitors. In the MBH, PIF was evenly distributed in the 17,000 g supernatant (S2) and in the crude mitochondrial fraction (P2) which contains synaptosomes. PIF activity was completely removed by alumina adsorption of S2, but not of P2 in spite of an over 99.9% elimination of DA. In contrast, striatal PIF activity was detected only in P2, and disappeared completely upon alumina adsorption, thus indicating that, in this structure, it is entirely due to DA. Addition of haloperidol (10--5M) or alpha-flupentixol (10--6M) reduced PIF activity of crude MBH homogenates, but no longer affected it after alumina adsorption. Quantitative studies suggest that only half of the total MBH PIF activity is accounted for by DA. It is concluded that the MBH contains dopamine-free PIF, which, as already shown for several other neurohormones, is exclusively distributed in nerve-endings.", "contents": "Prolactin inhibiting activity of dopamine-free subcellular fractions from rat mediobasal hypothalamus. In order to check the hypothesis of an identity of dopamine (DA) and prolactin inhibiting activity (PIF), their subcellular distribution was studied in the mediobasal hypothalamus (MBH) and the striatum, which served as a control structure. PIF was tested both in vivo and on pituitary incubates. Fractions were also assayed after adsorption of their catecholamine content on alumina, as well as in presence of haloperidol or alpha-flupentixol, potent DA receptor inhibitors. In the MBH, PIF was evenly distributed in the 17,000 g supernatant (S2) and in the crude mitochondrial fraction (P2) which contains synaptosomes. PIF activity was completely removed by alumina adsorption of S2, but not of P2 in spite of an over 99.9% elimination of DA. In contrast, striatal PIF activity was detected only in P2, and disappeared completely upon alumina adsorption, thus indicating that, in this structure, it is entirely due to DA. Addition of haloperidol (10--5M) or alpha-flupentixol (10--6M) reduced PIF activity of crude MBH homogenates, but no longer affected it after alumina adsorption. Quantitative studies suggest that only half of the total MBH PIF activity is accounted for by DA. It is concluded that the MBH contains dopamine-free PIF, which, as already shown for several other neurohormones, is exclusively distributed in nerve-endings."}
{"id": "PMID:24820", "title": "An atypical form of Sandhoff's disease. Case report and biochemical studies.", "content": "A case of Sandhoff's disease (GM2 gangliosidosis type 2) is reported because of an unusual course with later onset of symptoms, more slow progress and longer survival than those previously described. Otherwise the patient presented most of the classical symptoms of the disease with a final state of blindness, deafness and decerebrate rigidity. The residual acidic hexosaminidase isozymes in liver and brain tissue were Hex A and Hex S, while Hex B was barely detectable. The neutral hexosaminidase form called Hex C was also found. Two urinary oligosaccharides containing N-acetylglucosamine and mannose were found to be execreted by the patient.", "contents": "An atypical form of Sandhoff's disease. Case report and biochemical studies. A case of Sandhoff's disease (GM2 gangliosidosis type 2) is reported because of an unusual course with later onset of symptoms, more slow progress and longer survival than those previously described. Otherwise the patient presented most of the classical symptoms of the disease with a final state of blindness, deafness and decerebrate rigidity. The residual acidic hexosaminidase isozymes in liver and brain tissue were Hex A and Hex S, while Hex B was barely detectable. The neutral hexosaminidase form called Hex C was also found. Two urinary oligosaccharides containing N-acetylglucosamine and mannose were found to be execreted by the patient."}
{"id": "PMID:24822", "title": "Bilateral adrenalectomy: factors affecting hepatic protein synthesis following a single tube-feeding of tryptophan.", "content": "Effect of tryptophan force-feeding to well-fed adrenalectomized rats on the ability of liver cell sap and initiation factors to support protein synthesis in vitro was investigated. 5 h after tryptophan force-feeding, the capacity of liver cell sap, pH 5 enzyme and pH 5 supernatant to support protein synthesis was greatly increased. The capacity of cell sap to support charging of tRNA with either (14C)-leucine or (14C)-phenylalanine was increased following a dose of tryptophan. Initiation factors prepared from tryptophan-fed adrenalectomized rats stimulated polyuridylic-acid-directed polyphenylalanine synthesis to a greater extent than those from livers of water-fed adrenalectomized controls.", "contents": "Bilateral adrenalectomy: factors affecting hepatic protein synthesis following a single tube-feeding of tryptophan. Effect of tryptophan force-feeding to well-fed adrenalectomized rats on the ability of liver cell sap and initiation factors to support protein synthesis in vitro was investigated. 5 h after tryptophan force-feeding, the capacity of liver cell sap, pH 5 enzyme and pH 5 supernatant to support protein synthesis was greatly increased. The capacity of cell sap to support charging of tRNA with either (14C)-leucine or (14C)-phenylalanine was increased following a dose of tryptophan. Initiation factors prepared from tryptophan-fed adrenalectomized rats stimulated polyuridylic-acid-directed polyphenylalanine synthesis to a greater extent than those from livers of water-fed adrenalectomized controls."}
{"id": "PMID:24828", "title": "Sodium and chloride transport in the isolated human cornea.", "content": "22Na and 36Cl fluxes in isolated human cornea preparations were measured under short-circuited conditions. At pH 7.3-PH 7.6 sodium net flux was directed from aqueous humour to tear side, chloride net flux was statistically not different from zero. Alkalinization of the bathing solution to pH 8.6 stimulated unidirectional sodium and chloride fluxes from aqueous humour to tear side resulting in net sodium and chloride fluxes towards the tear side which both were statistically different from zero. Cyclic AMP (10(-3) M) was found to stimulate sodium and chloride unidirectional fluxes from aqueous humour to tear side, thus leading to significant net sodium and chloride fluxes in the same direction. Epinephrine (10(-4) M) increased the unidirectional chloride flux from aqueous humour to tear side more pronounced than in the opposite direction, producing a significant net chloride flux towards the tear side. The results are consistent with the hypothesis that the electrolyte pumps may under certain conditions contribute to the dehydration of the stroma.", "contents": "Sodium and chloride transport in the isolated human cornea. 22Na and 36Cl fluxes in isolated human cornea preparations were measured under short-circuited conditions. At pH 7.3-PH 7.6 sodium net flux was directed from aqueous humour to tear side, chloride net flux was statistically not different from zero. Alkalinization of the bathing solution to pH 8.6 stimulated unidirectional sodium and chloride fluxes from aqueous humour to tear side resulting in net sodium and chloride fluxes towards the tear side which both were statistically different from zero. Cyclic AMP (10(-3) M) was found to stimulate sodium and chloride unidirectional fluxes from aqueous humour to tear side, thus leading to significant net sodium and chloride fluxes in the same direction. Epinephrine (10(-4) M) increased the unidirectional chloride flux from aqueous humour to tear side more pronounced than in the opposite direction, producing a significant net chloride flux towards the tear side. The results are consistent with the hypothesis that the electrolyte pumps may under certain conditions contribute to the dehydration of the stroma."}
{"id": "PMID:24829", "title": "[Treatment of acute asthma. Comparison of the effectiveness of corticosteroids and of a combination of corticosteroids and an adrenergic beta-stimulant (author's transl)].", "content": "Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication.", "contents": "[Treatment of acute asthma. Comparison of the effectiveness of corticosteroids and of a combination of corticosteroids and an adrenergic beta-stimulant (author's transl)]. Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication."}
{"id": "PMID:24833", "title": "Overmethylation of DNAs by the EcoRI methylase.", "content": "EcoRI methylase is able to catalyze methy incorporation into DNA at sequences other than the canonical EcoRI site. At high enzyme concentrations and over a wide range of pH and ionic strengths, EcoRI methylase modifies polyoma DNA (which contains one EcoRI site) at a number of sites. This modification prevents EcoRI endonuclease activity, and thus is presumably at or near the EcoRI sequences (5') NAATTN.", "contents": "Overmethylation of DNAs by the EcoRI methylase. EcoRI methylase is able to catalyze methy incorporation into DNA at sequences other than the canonical EcoRI site. At high enzyme concentrations and over a wide range of pH and ionic strengths, EcoRI methylase modifies polyoma DNA (which contains one EcoRI site) at a number of sites. This modification prevents EcoRI endonuclease activity, and thus is presumably at or near the EcoRI sequences (5') NAATTN."}
{"id": "PMID:24834", "title": "Mammalian tRNA sulfurtransferase: properties of the enzyme in rat liver.", "content": "Transfer RNA sulfurtransferase activity was detected in 105,000 x g supernatant preparations from rat liver and several other rat tissues. Sulfur is transferred from [35S] cysteine to tRNA in a reaction which also requires ATP, Mg2+, and supernatant protein. While [35S] beta-mercaptopyruvate appeared to be a substrate for this enzyme, the reaction product was sensitive to deacylation and the reaction was inhibited by [32S] cysteine. Of the various nucleic acids tested, only tRNAs were effective sulfur acceptors, with rat liver tRNA being the poorest substrate. The [35S] reaction product was sensitive to ribonuclease, cochromatographed with tRNA on methylated-albumin kieselguhr columns, and was converted to nucleotide material after alkaline hydrolysis. DEAE-cellulose chromatography of the neutralized [35S] nucleotide digest revealed a single thionucleotide peak. These studies demonstrate that tRNA sulfurtransferase is present in various rat tissues, and that the requirements of the liver enzyme are similar to those of bacterial enzymes.", "contents": "Mammalian tRNA sulfurtransferase: properties of the enzyme in rat liver. Transfer RNA sulfurtransferase activity was detected in 105,000 x g supernatant preparations from rat liver and several other rat tissues. Sulfur is transferred from [35S] cysteine to tRNA in a reaction which also requires ATP, Mg2+, and supernatant protein. While [35S] beta-mercaptopyruvate appeared to be a substrate for this enzyme, the reaction product was sensitive to deacylation and the reaction was inhibited by [32S] cysteine. Of the various nucleic acids tested, only tRNAs were effective sulfur acceptors, with rat liver tRNA being the poorest substrate. The [35S] reaction product was sensitive to ribonuclease, cochromatographed with tRNA on methylated-albumin kieselguhr columns, and was converted to nucleotide material after alkaline hydrolysis. DEAE-cellulose chromatography of the neutralized [35S] nucleotide digest revealed a single thionucleotide peak. These studies demonstrate that tRNA sulfurtransferase is present in various rat tissues, and that the requirements of the liver enzyme are similar to those of bacterial enzymes."}
{"id": "PMID:24835", "title": "Choosing a drug regimen for obstructive pulmonary disease. 1. Agents to achieve bronchodilatation.", "content": "Many patients with pulmonary disease may have significant airflow obstruction. Bronchodilatation is an important aspect of treatment and can be achieved with beta-adrenergic agonists, methylxanthine derivatives, and anticholinergic agents. These can be used singly or in combination, depending on the severity of obstruction.", "contents": "Choosing a drug regimen for obstructive pulmonary disease. 1. Agents to achieve bronchodilatation. Many patients with pulmonary disease may have significant airflow obstruction. Bronchodilatation is an important aspect of treatment and can be achieved with beta-adrenergic agonists, methylxanthine derivatives, and anticholinergic agents. These can be used singly or in combination, depending on the severity of obstruction."}
{"id": "PMID:24836", "title": "Multiple endocrine adenomatosis (Type I) and familial hyperparathyroidism.", "content": "Hyperparathyroidism is the commonest presenting feature in multiple endocrine adenomatosis Type I (MEA Type I), the other manifestations may be delayed for many years or appear only in relatives. A family now diagnosed as MEA Type I, who was previously thought, in 1965, to have familial hyperparathyroidism due to chief cell hyperplasia is now described. The importance is stressed of family surveillance and long-term follow-up in all cases of primary hyperparathyroidism. Those tests that are essential in the long-term surveillance of the patients and their first degree relatives are discussed.", "contents": "Multiple endocrine adenomatosis (Type I) and familial hyperparathyroidism. Hyperparathyroidism is the commonest presenting feature in multiple endocrine adenomatosis Type I (MEA Type I), the other manifestations may be delayed for many years or appear only in relatives. A family now diagnosed as MEA Type I, who was previously thought, in 1965, to have familial hyperparathyroidism due to chief cell hyperplasia is now described. The importance is stressed of family surveillance and long-term follow-up in all cases of primary hyperparathyroidism. Those tests that are essential in the long-term surveillance of the patients and their first degree relatives are discussed."}
{"id": "PMID:24838", "title": "[Papain immobilization on a fibrous polymer of polyvinyl alcohol].", "content": "The paper discusses papain immobilization on modified polyvinyl alcohol fibers by the ion fixation technique. The effect of the chemical structure of polyvinyl alcohol fibers on the basic properties of the bound enzyme has been examined. The level of activity and tolerance to pH changes of the resultant immobilized enzymes have been shown to depend on the papain arrangement in the polymer molecule.", "contents": "[Papain immobilization on a fibrous polymer of polyvinyl alcohol]. The paper discusses papain immobilization on modified polyvinyl alcohol fibers by the ion fixation technique. The effect of the chemical structure of polyvinyl alcohol fibers on the basic properties of the bound enzyme has been examined. The level of activity and tolerance to pH changes of the resultant immobilized enzymes have been shown to depend on the papain arrangement in the polymer molecule."}
{"id": "PMID:24839", "title": "[Immobilization of alpha-amylase on porous glass and silochrome].", "content": "Immobilized forms of alpha-amylase from Aspergillus oryzae were prepared on the porous glass and silochrome by the glutaraldehyde method. An addition of calcium ions at a concentration of 0.05 M to the reaction mixture during immobilization stabilized the enzyme activity. pH optimum of the insoluble form of alpha-amylase was 5.8 and that of the soluble form was 4.7. Storage of the insoluble enzyme as water suspension in 0.015 M CaCl2 at 4 degrees C for six months and twenty times repeated specific reaction did not affect significantly the activity of insoluble alpha-amylase.", "contents": "[Immobilization of alpha-amylase on porous glass and silochrome]. Immobilized forms of alpha-amylase from Aspergillus oryzae were prepared on the porous glass and silochrome by the glutaraldehyde method. An addition of calcium ions at a concentration of 0.05 M to the reaction mixture during immobilization stabilized the enzyme activity. pH optimum of the insoluble form of alpha-amylase was 5.8 and that of the soluble form was 4.7. Storage of the insoluble enzyme as water suspension in 0.015 M CaCl2 at 4 degrees C for six months and twenty times repeated specific reaction did not affect significantly the activity of insoluble alpha-amylase."}
{"id": "PMID:24840", "title": "[Glutamine synthetase immobilization].", "content": "Highly purified glutamine synthetase has been isolated from Chlorella and immobilized on BrCN-sepharose. Its residual activity was 25-35%. Immobilized glutamine synthetase showed far greater thermal stability than glutamine synthetase in solution. During immobilization pH optimum of the enzyme was shifted towards the alkaline area, maximum rate of the reaction was reduced and KM remained unaltered.", "contents": "[Glutamine synthetase immobilization]. Highly purified glutamine synthetase has been isolated from Chlorella and immobilized on BrCN-sepharose. Its residual activity was 25-35%. Immobilized glutamine synthetase showed far greater thermal stability than glutamine synthetase in solution. During immobilization pH optimum of the enzyme was shifted towards the alkaline area, maximum rate of the reaction was reduced and KM remained unaltered."}
{"id": "PMID:24844", "title": "Interaction of human chorionic gonadotropin with membrane components of rat testes.", "content": "Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message across the target cell membrane. As a continuation of these investigations, we examined the effects of down-regulation of hCG receptors on the interaction of hCG with rat testis membrane components. Rat testes contained a complex ganglioside pattern that did not appear to change qualitatively or quantitatively after the injection of hCG into the animals, although testis membranes from hCG-treated rats lost their capacity to bind (125)I-labeled hCG ((125)I-hCG). Gangliosides extracted from the testes of control and treated animals were equally effective inhibitors of (125)I-hCG binding to testis membranes. However, inhibition of binding was observed only under conditions (pH 6.0, low ionic strength) such that unlabeled hCG (>2500-fold excess) did not block (125)I-hCG binding, and (125)I-hCG bound similarly to testis membranes from control and treated rats. Under conditions such that hCG binding was specific (blocked by 250-fold excess of unlabeled hCG), testis gangliosides were noninhibitory. Liposomes containing gangliosides from the testes of control or hCG-treated rats bound similar small amounts of (125)I-hCG. These same liposomes bound 50 and 1000 times more thyrotropin and cholera toxin, respectively, than hCG. Oligosaccharides derived from gangliosides did not inhibit (125)I-hCG binding to testis membranes nor did they alter the fluorescence of hCG conjugated with fluorescent probes, whereas the gangliosides themselves were inhibitory and enhanced the fluorescence intensity of the hCG derivatives. Exposure of testis membranes from hCG-treated rats to 4 M MgCl(2), which displaces bound hCG [Chen, Y.-D. I. & Payne, A. H. (1977) Biochem. Biophys. Res. Commun. 74, 1589-1596], did not restore their ability to bind (125)I-hCG. When membranes were solubilized with Triton X-100, a solubilized receptor was detected from testis membranes of control but not hCG-treated rats. These findings and the absence of demonstrable changes in the composition or quantity of rat testis gangliosides when hCG receptors are down-regulated suggest that gangliosides do not represent the primary binding determinants of hCG receptors.", "contents": "Interaction of human chorionic gonadotropin with membrane components of rat testes. Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message across the target cell membrane. As a continuation of these investigations, we examined the effects of down-regulation of hCG receptors on the interaction of hCG with rat testis membrane components. Rat testes contained a complex ganglioside pattern that did not appear to change qualitatively or quantitatively after the injection of hCG into the animals, although testis membranes from hCG-treated rats lost their capacity to bind (125)I-labeled hCG ((125)I-hCG). Gangliosides extracted from the testes of control and treated animals were equally effective inhibitors of (125)I-hCG binding to testis membranes. However, inhibition of binding was observed only under conditions (pH 6.0, low ionic strength) such that unlabeled hCG (>2500-fold excess) did not block (125)I-hCG binding, and (125)I-hCG bound similarly to testis membranes from control and treated rats. Under conditions such that hCG binding was specific (blocked by 250-fold excess of unlabeled hCG), testis gangliosides were noninhibitory. Liposomes containing gangliosides from the testes of control or hCG-treated rats bound similar small amounts of (125)I-hCG. These same liposomes bound 50 and 1000 times more thyrotropin and cholera toxin, respectively, than hCG. Oligosaccharides derived from gangliosides did not inhibit (125)I-hCG binding to testis membranes nor did they alter the fluorescence of hCG conjugated with fluorescent probes, whereas the gangliosides themselves were inhibitory and enhanced the fluorescence intensity of the hCG derivatives. Exposure of testis membranes from hCG-treated rats to 4 M MgCl(2), which displaces bound hCG [Chen, Y.-D. I. & Payne, A. H. (1977) Biochem. Biophys. Res. Commun. 74, 1589-1596], did not restore their ability to bind (125)I-hCG. When membranes were solubilized with Triton X-100, a solubilized receptor was detected from testis membranes of control but not hCG-treated rats. These findings and the absence of demonstrable changes in the composition or quantity of rat testis gangliosides when hCG receptors are down-regulated suggest that gangliosides do not represent the primary binding determinants of hCG receptors."}
{"id": "PMID:24841", "title": "[Purification and properties of the NADP-specific glutamate dehydrogenase of Candida tropicalis feed yeasts].", "content": "From the cell-free extract of fodder yeast Candida tropicalis NADP-specific glutamate dehydrogenase was isolated and partially purified (75-fold) by means of fractional precipitation by ammonium sulphate and ion-exchange chromatography on DEAE-cellulose. The preparation was investigated with the aid of polyacrylamide gel electrophoresis. Kinetic characteristics of the enzyme in the cell-free extract and partially purified preparation were derived.", "contents": "[Purification and properties of the NADP-specific glutamate dehydrogenase of Candida tropicalis feed yeasts]. From the cell-free extract of fodder yeast Candida tropicalis NADP-specific glutamate dehydrogenase was isolated and partially purified (75-fold) by means of fractional precipitation by ammonium sulphate and ion-exchange chromatography on DEAE-cellulose. The preparation was investigated with the aid of polyacrylamide gel electrophoresis. Kinetic characteristics of the enzyme in the cell-free extract and partially purified preparation were derived."}
{"id": "PMID:24845", "title": "Role of anions in parathyroid hormone release from dispersed bovine parathyroid cells.", "content": "It is known that permeant anions are required for the release of epinephrine from isolated chromaffin granules and of serotonin from intact platelets. We have now investigated the role of anions in the release of a polypeptide hormone, parathyroid hormone, from dispersed bovine parathyroid cells. The release is inhibited 60%-80% by decreasing either [Cl-] or [OH-] and 60%-70% by replacement of NaCl with the impermeant anion isethionate. By contrast, substitution of various monovalent cations in the medium had no effect on the release. Disodium 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and probenecid, which are known to block anion transport in the erythrocyte, also cause a dose-dependent 90%-100% inhibition of release. Moreover, kinetic analysis of inhibition by probenecid suggests that it is competitive with respect to either OH- or Cl-. These results suggest that anions and the anion transport system may play a role in exocytosis of a polypeptide hormone. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone was was also found to block hormone release, and the possibility is discussed of a \"chemosmotic\" mechanism for exocytosis in this system similar to that previously postulated for chromaffin granules and platelets.", "contents": "Role of anions in parathyroid hormone release from dispersed bovine parathyroid cells. It is known that permeant anions are required for the release of epinephrine from isolated chromaffin granules and of serotonin from intact platelets. We have now investigated the role of anions in the release of a polypeptide hormone, parathyroid hormone, from dispersed bovine parathyroid cells. The release is inhibited 60%-80% by decreasing either [Cl-] or [OH-] and 60%-70% by replacement of NaCl with the impermeant anion isethionate. By contrast, substitution of various monovalent cations in the medium had no effect on the release. Disodium 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and probenecid, which are known to block anion transport in the erythrocyte, also cause a dose-dependent 90%-100% inhibition of release. Moreover, kinetic analysis of inhibition by probenecid suggests that it is competitive with respect to either OH- or Cl-. These results suggest that anions and the anion transport system may play a role in exocytosis of a polypeptide hormone. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone was was also found to block hormone release, and the possibility is discussed of a \"chemosmotic\" mechanism for exocytosis in this system similar to that previously postulated for chromaffin granules and platelets."}
{"id": "PMID:24846", "title": "Phosphate metabolites in lymphoid, Friend erythroleukemia, and HeLa cells observed by high-resolution 31P nuclear magnetic resonance.", "content": "High-resolution phosphorus-31 nuclear magnetic resonance spectra were observed for cell lines from mammalian sources: lymphoid cells, Friend erythroleukemia cells, and HeLa cells. Some phosphate metabolites were identified and their concentrations were found to vary among the different cell lines. ATP/ADP ratios could be measured in the living cells. The phospholipid metabolites phosphorylcholine and phosphorylethanolamine and their glyceryl esters were present in relatively high concentrations in the cells, but their ratios varied considerably. Also, a high concentration of an unidentified diphosphodiester compound was observed in the Friend erythroleukemia and HeLa cells. No appreciable pH gradient across the cell membrance was observed in these three mammalian cell lines, in contrast to the large pH gradient detected in microorganisms.", "contents": "Phosphate metabolites in lymphoid, Friend erythroleukemia, and HeLa cells observed by high-resolution 31P nuclear magnetic resonance. High-resolution phosphorus-31 nuclear magnetic resonance spectra were observed for cell lines from mammalian sources: lymphoid cells, Friend erythroleukemia cells, and HeLa cells. Some phosphate metabolites were identified and their concentrations were found to vary among the different cell lines. ATP/ADP ratios could be measured in the living cells. The phospholipid metabolites phosphorylcholine and phosphorylethanolamine and their glyceryl esters were present in relatively high concentrations in the cells, but their ratios varied considerably. Also, a high concentration of an unidentified diphosphodiester compound was observed in the Friend erythroleukemia and HeLa cells. No appreciable pH gradient across the cell membrance was observed in these three mammalian cell lines, in contrast to the large pH gradient detected in microorganisms."}
{"id": "PMID:24847", "title": "Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata).", "content": "We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is though to be involved in cell growth, DNA and RNA synthesis, and possible malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3H]thymidine incorporation into cultured splenic lymphocytes, a process thought to be mediated by cyclic GMP. The results demonstrate that the extract of the balsam pear blocks both the growth of the rat prostatic adencarcinoma in vitro and [3H]thymidine incorporation into DNA. DNA histograms from flow cytometry indicated that the extract containing GCI inhibited in the G2 + M phase of the cell cycle, a presumed locus of cyclic GMP effects. In addition, guanylate cyclase activity was significantly greater in the tumor than normal prostate tissue and was decreased by the extract containing GCI. Cyclic GMP levels in the tumor in culture wer also decreased by addition of the extract. It remains to be determined whether or not the anti-tumor agent and GCI are the same substance.", "contents": "Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata). We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is though to be involved in cell growth, DNA and RNA synthesis, and possible malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3H]thymidine incorporation into cultured splenic lymphocytes, a process thought to be mediated by cyclic GMP. The results demonstrate that the extract of the balsam pear blocks both the growth of the rat prostatic adencarcinoma in vitro and [3H]thymidine incorporation into DNA. DNA histograms from flow cytometry indicated that the extract containing GCI inhibited in the G2 + M phase of the cell cycle, a presumed locus of cyclic GMP effects. In addition, guanylate cyclase activity was significantly greater in the tumor than normal prostate tissue and was decreased by the extract containing GCI. Cyclic GMP levels in the tumor in culture wer also decreased by addition of the extract. It remains to be determined whether or not the anti-tumor agent and GCI are the same substance."}
{"id": "PMID:24842", "title": "[Microbiological transformation of carbohydrates. Glucose isomerization into fructose by washed cells of Streptomyces sp. strain 29].", "content": "Glucose-fructose transformation by washed and packed cells of Streptomyces sp. 29 was studied. The cells grown on the nutrient medium containing xylose and Co and Mg salts were capable to perform glucose-fructose isomerization. The cellular activity depended in a great degree on the temperature, pH and initial glucose concentration; to a lesser extent on Co and Mg ions present in the incubation mixture, and did not depend on the age of the culture (within 8-69 hours). The activity reached its maximum at 70-80 degrees C, pH 7.0 and a low concentration of glucose (10(-3) M). Under these conditions the yield of fructose was 50% from the initial glucose concentration (or 100% from the theoretical value). Washed cells of Streptomyces sp. 29 packed into a thermally controlled column continuously transformed glucose to fructose during 24 days with a yield of 30-44%.", "contents": "[Microbiological transformation of carbohydrates. Glucose isomerization into fructose by washed cells of Streptomyces sp. strain 29]. Glucose-fructose transformation by washed and packed cells of Streptomyces sp. 29 was studied. The cells grown on the nutrient medium containing xylose and Co and Mg salts were capable to perform glucose-fructose isomerization. The cellular activity depended in a great degree on the temperature, pH and initial glucose concentration; to a lesser extent on Co and Mg ions present in the incubation mixture, and did not depend on the age of the culture (within 8-69 hours). The activity reached its maximum at 70-80 degrees C, pH 7.0 and a low concentration of glucose (10(-3) M). Under these conditions the yield of fructose was 50% from the initial glucose concentration (or 100% from the theoretical value). Washed cells of Streptomyces sp. 29 packed into a thermally controlled column continuously transformed glucose to fructose during 24 days with a yield of 30-44%."}
{"id": "PMID:24843", "title": "[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes].", "content": "Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.", "contents": "[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide."}
{"id": "PMID:24855", "title": "Fluorimetric determination of the active form of tetracycline, chloretetracycline and oxytetracycline in partially decomposed solutions.", "content": "The content of tetracycline (1), chlortetracycline (2) and oxytetracycline (3) has been determined by use of the fluorimetric method in partially decomposed acqueous solutions of different pH values. The procedure consisted in the extraction of fluorescent calcium and 5.5-diethyl-barbituric acid complexes of 1 and 3 (with 2 calcium complex only) into an organic solvent. In the method, only complexes with undecomposed 1--3 show a strong fluorescence. Products of decomposition of the antibiotics did not affect significantly analytical results. Comparative investigations have been carried out with 1--3 using t.l.c. and turbidimetry.", "contents": "Fluorimetric determination of the active form of tetracycline, chloretetracycline and oxytetracycline in partially decomposed solutions. The content of tetracycline (1), chlortetracycline (2) and oxytetracycline (3) has been determined by use of the fluorimetric method in partially decomposed acqueous solutions of different pH values. The procedure consisted in the extraction of fluorescent calcium and 5.5-diethyl-barbituric acid complexes of 1 and 3 (with 2 calcium complex only) into an organic solvent. In the method, only complexes with undecomposed 1--3 show a strong fluorescence. Products of decomposition of the antibiotics did not affect significantly analytical results. Comparative investigations have been carried out with 1--3 using t.l.c. and turbidimetry."}
{"id": "PMID:24859", "title": "The effect of stress on the activity of hepatic tryptophan pyrrolase, of tyrosine aminotransferase in various organs and on the level of tryptophan in the liver and plasma of rats.", "content": "In rats subjected to 400 revolutions in Noble-Collip drums, hepatic tryptophan pyrrolase activity increases and plasma tryptophan level decreases. After bilateral adrenalectomy, the alterations of plasma tryptophan are even more pronounced and liver tryptophan increases in contrast to tryptophan pyrrolase activity which remains unchanged after injury. The possible significance of the posttraumatic increase of tryptophan pyrrolase in intact animals for brain serotonin metabolism and hepatic gluconeogenesis is underlined. The activity of tyrosine aminotransferase in liver, brain, adrenal, kidney and muscle tissue of rats was determined with special reference to the possible effect of the before-mentioned stress procedure. Organ homogenates were centrifuged at 15000 x g and both supernatants and pellets were investigated for enzyme activity with the exception of the liver, where only the supernatant fraction was used. Tyrosine aminotransferase activity in the liver supernatant considerably exceeded the corresponding values in both supernatant and pellet of the remaining organs, in which a prevalence of the mitochondrial enzyme was obvious. In contrast to the clear-cut increase of the hepatic enzyme during stress, essentially no changes were noted in the brain, the adrenals, kidney or muscle under similar conditions...", "contents": "The effect of stress on the activity of hepatic tryptophan pyrrolase, of tyrosine aminotransferase in various organs and on the level of tryptophan in the liver and plasma of rats. In rats subjected to 400 revolutions in Noble-Collip drums, hepatic tryptophan pyrrolase activity increases and plasma tryptophan level decreases. After bilateral adrenalectomy, the alterations of plasma tryptophan are even more pronounced and liver tryptophan increases in contrast to tryptophan pyrrolase activity which remains unchanged after injury. The possible significance of the posttraumatic increase of tryptophan pyrrolase in intact animals for brain serotonin metabolism and hepatic gluconeogenesis is underlined. The activity of tyrosine aminotransferase in liver, brain, adrenal, kidney and muscle tissue of rats was determined with special reference to the possible effect of the before-mentioned stress procedure. Organ homogenates were centrifuged at 15000 x g and both supernatants and pellets were investigated for enzyme activity with the exception of the liver, where only the supernatant fraction was used. Tyrosine aminotransferase activity in the liver supernatant considerably exceeded the corresponding values in both supernatant and pellet of the remaining organs, in which a prevalence of the mitochondrial enzyme was obvious. In contrast to the clear-cut increase of the hepatic enzyme during stress, essentially no changes were noted in the brain, the adrenals, kidney or muscle under similar conditions..."}
{"id": "PMID:24860", "title": "[Behavioral rehabilitation of nonspecific symptoms occuring after craniocerbral trauma (author's transl)].", "content": "The purpose of this study was to develop a behavioral rehabilitation program for patients with long-term nonspecific symptoms following craniocerebral trauma. In 47 patients we analyzed symptoms typical of \"illness behavior\" (e.g. complaining tendency, depression, irritability, psychosomatic pain, problems in job performance and social interaction) as possible targets for behavior modification. We then developed a behavioral training program to teach the patients various techniques of self-control (relaxation, desensitization, self-image training, analysis and control of illness behavior, assertiveness, performance techniques), our program being based on studies in the U.S.A. using similar approaches. For a preliminary testing two groups of 8 and 6 patients each were treated by different therapists. The patients worked through a section of the program manual prior to each group session. During the sessions proper (a total of 8 weekly two-hour sessions) the different techniques were practiced under the therapist's supervistion. In both groups a significant reduction in illness behavior as indicated on questionnaires and in 3-month follow-up was found. These encouraging results need to be further substantiated by controlled outcome studies.", "contents": "[Behavioral rehabilitation of nonspecific symptoms occuring after craniocerbral trauma (author's transl)]. The purpose of this study was to develop a behavioral rehabilitation program for patients with long-term nonspecific symptoms following craniocerebral trauma. In 47 patients we analyzed symptoms typical of \"illness behavior\" (e.g. complaining tendency, depression, irritability, psychosomatic pain, problems in job performance and social interaction) as possible targets for behavior modification. We then developed a behavioral training program to teach the patients various techniques of self-control (relaxation, desensitization, self-image training, analysis and control of illness behavior, assertiveness, performance techniques), our program being based on studies in the U.S.A. using similar approaches. For a preliminary testing two groups of 8 and 6 patients each were treated by different therapists. The patients worked through a section of the program manual prior to each group session. During the sessions proper (a total of 8 weekly two-hour sessions) the different techniques were practiced under the therapist's supervistion. In both groups a significant reduction in illness behavior as indicated on questionnaires and in 3-month follow-up was found. These encouraging results need to be further substantiated by controlled outcome studies."}
{"id": "PMID:24866", "title": "Oxygen affinity and 2,3-diphosphoglycerate in blood of Australian marsupials of differing body size.", "content": "Oxygen carriage and 2,3-diphosphoglycerate (2,3-DPG) levels have been measured in the blood of seven species of Australian marsupials ranging in size from 35 to 0.03 kg. They were Red and Grey Kangaroos, Wallaroo, Tammar Wallaby, Brush-tailed possum, Potoroo, and Brown Marsupial Mouse. Oxygen affinity decreased with decrease in adult body size, standard P50 (at 36 C) varying from 24.6 torr in the largest (Red Kangaroo) to 41.9 torr in the smallest (Brown Marsupial Mouse). The relationship between P50 and body size is similar to the relationship which has been described previously for eutherian mammals. The Bohr factor (--deltalog P50/deltapH) and value for Hill n were generally in the range found for other land-dwelling mammals. All species had 2,3-DPG in their erythrocytes acting as a regulator of oxygen affinity. The polymorphism at position beta 2 in hemoglobin of the Grey Kangaroo was shown to affect the respiratory properties of the molecule. When beta 2 = histidine, which has a positively charged side chain, erythrocyte 2,3-DPG was higher, and P50 was higher, than when beta 2 = glutamine which has a neutral side chain.", "contents": "Oxygen affinity and 2,3-diphosphoglycerate in blood of Australian marsupials of differing body size. Oxygen carriage and 2,3-diphosphoglycerate (2,3-DPG) levels have been measured in the blood of seven species of Australian marsupials ranging in size from 35 to 0.03 kg. They were Red and Grey Kangaroos, Wallaroo, Tammar Wallaby, Brush-tailed possum, Potoroo, and Brown Marsupial Mouse. Oxygen affinity decreased with decrease in adult body size, standard P50 (at 36 C) varying from 24.6 torr in the largest (Red Kangaroo) to 41.9 torr in the smallest (Brown Marsupial Mouse). The relationship between P50 and body size is similar to the relationship which has been described previously for eutherian mammals. The Bohr factor (--deltalog P50/deltapH) and value for Hill n were generally in the range found for other land-dwelling mammals. All species had 2,3-DPG in their erythrocytes acting as a regulator of oxygen affinity. The polymorphism at position beta 2 in hemoglobin of the Grey Kangaroo was shown to affect the respiratory properties of the molecule. When beta 2 = histidine, which has a positively charged side chain, erythrocyte 2,3-DPG was higher, and P50 was higher, than when beta 2 = glutamine which has a neutral side chain."}
{"id": "PMID:24867", "title": "Metabolic, respiratory and haematological adjustments of the little pocket mouse to circadian torpor cycles.", "content": "Metabolic, respiratory and haematological parameters were investigated for the Little Pocket mouse during circadian torpor cycles. The rate of O2 consumption decreased from 7.04 to 0.05 ml O2.g-1.hr-1, with a corresponding decrease in respiratory minute volume from 49.4 to 0.9 ml.min-1 during torpor at an ambient temperature of 10 C. No changes in haemoglobin concentration (19.7 g/100 ml), haematocrit (54%), red blood corpuscle count (12.4 10(6)/microliter), mean corpuscular volume (43.6 micrometer3), mean corpuscular haemoglobin content (16.2 pg), mean corpuscular haemoglobin concentration (37.4%) and [2,3-DPG] (9.6 mumol/g Hb) were observed during torpor cycles. The half saturation tension of P. longimembris haemoglobin was 41 mm Hg (37 C, pH = 7.28) and 19.7 mm Hg (10 degrees C, pH = 7.51). The effect of temperature on P50 was deltalog P50/ C = +0.0106 (pH = 7.4). Venous blood parameters were: euthermic mice (37 C); PCO2 = 36.8 mm Hg, PO2 = 49.5 mm Hg, pH = 7.28, [HCO-3] = 17.3 mmol/l; torpid mice (10 C); PCO2 = 14.6, PO2 = 35.7 pH = 7.51, [HCO-3] = 18.8. These data indicate a new, relatively acidotic acid-base status during torpor, characterised by a higher H+/ OH- ratio. The respiratory sensitivity to inspired CO2 of pocket mice was, despite their being semi-fossorial, typical of other mammals. High concentrations of CO2 did not induce, or facilitate, entry into torpor.", "contents": "Metabolic, respiratory and haematological adjustments of the little pocket mouse to circadian torpor cycles. Metabolic, respiratory and haematological parameters were investigated for the Little Pocket mouse during circadian torpor cycles. The rate of O2 consumption decreased from 7.04 to 0.05 ml O2.g-1.hr-1, with a corresponding decrease in respiratory minute volume from 49.4 to 0.9 ml.min-1 during torpor at an ambient temperature of 10 C. No changes in haemoglobin concentration (19.7 g/100 ml), haematocrit (54%), red blood corpuscle count (12.4 10(6)/microliter), mean corpuscular volume (43.6 micrometer3), mean corpuscular haemoglobin content (16.2 pg), mean corpuscular haemoglobin concentration (37.4%) and [2,3-DPG] (9.6 mumol/g Hb) were observed during torpor cycles. The half saturation tension of P. longimembris haemoglobin was 41 mm Hg (37 C, pH = 7.28) and 19.7 mm Hg (10 degrees C, pH = 7.51). The effect of temperature on P50 was deltalog P50/ C = +0.0106 (pH = 7.4). Venous blood parameters were: euthermic mice (37 C); PCO2 = 36.8 mm Hg, PO2 = 49.5 mm Hg, pH = 7.28, [HCO-3] = 17.3 mmol/l; torpid mice (10 C); PCO2 = 14.6, PO2 = 35.7 pH = 7.51, [HCO-3] = 18.8. These data indicate a new, relatively acidotic acid-base status during torpor, characterised by a higher H+/ OH- ratio. The respiratory sensitivity to inspired CO2 of pocket mice was, despite their being semi-fossorial, typical of other mammals. High concentrations of CO2 did not induce, or facilitate, entry into torpor."}
{"id": "PMID:24868", "title": "A comparative study of the respiratory properties of bird blood.", "content": "Oxygen affinity and Bohr effect have been measured in the blood of four bird species (chicken, pigeon, Japanese quail and sparrow). Under physiological conditions (41 C, pH 7.5, PCO2 approximately 35 Torr) the oxygen half saturation pressure P50 are 50 Torr for the chickens, 38 Torr for the pigeon, 43 Torr for the Japanese quail and 44 Torr for the sparrow. Values for the physiological Bohr factors deltalogP50/deltapH are similar to those obtained in mammalian blood ranging from -0.57 in chicken blood to -0.42 for pigeon blood. A direct effect of CO2 on the oxygen affinity of chicken blood could not be observed, in agreement with results in hemoglobin solutions. However, at a constant pHpl of 7.5 the intracellular pH rise from 7.22 at 39 Torr PCO2 to 7.32 at PCO2 less than 1 Torr. This leads to a decrease of P50 at pHpl 7.5 from 52 to 46 Torr. A convincing correlation between body weight and P50 could not be established, even when including data from other authors. It is concluded that aside from metabolic rate, behavioural as well as environmental factors have influenced whole blood oxygen affinity during evolution.", "contents": "A comparative study of the respiratory properties of bird blood. Oxygen affinity and Bohr effect have been measured in the blood of four bird species (chicken, pigeon, Japanese quail and sparrow). Under physiological conditions (41 C, pH 7.5, PCO2 approximately 35 Torr) the oxygen half saturation pressure P50 are 50 Torr for the chickens, 38 Torr for the pigeon, 43 Torr for the Japanese quail and 44 Torr for the sparrow. Values for the physiological Bohr factors deltalogP50/deltapH are similar to those obtained in mammalian blood ranging from -0.57 in chicken blood to -0.42 for pigeon blood. A direct effect of CO2 on the oxygen affinity of chicken blood could not be observed, in agreement with results in hemoglobin solutions. However, at a constant pHpl of 7.5 the intracellular pH rise from 7.22 at 39 Torr PCO2 to 7.32 at PCO2 less than 1 Torr. This leads to a decrease of P50 at pHpl 7.5 from 52 to 46 Torr. A convincing correlation between body weight and P50 could not be established, even when including data from other authors. It is concluded that aside from metabolic rate, behavioural as well as environmental factors have influenced whole blood oxygen affinity during evolution."}
{"id": "PMID:24869", "title": "Regulation of arterial PCO2 during inhalation of CO2 in chickens.", "content": "Since CO2-sensitive intrapulmonary chemoreceptors have been shown to exist in the avian lung, we conducted a series of experiments to determine if birds could regulate PaCO2 when confronted with an inspired CO2 load. Chickens were anesthetized with either pentobarbital (30 mg.kg-1) or phenobarbital (160 mg.kg-1). The PICO2 was either increased or decreased in successive 7 torr steps between 0 and 35 torr. At each level of PICO2, steady-state measurements of PaCO2, PaO2 and [H+]a were made. In three of ten experiments, tidal volume and respiratory frequency were determined and minute ventilation calculated. Our results indicate that as PICO2 is varied between 0 and 21 torr, minute ventilation increases and arterial homeostasis of PCO2 and [H+] is maintained; as the PICO2 is increased above 21 torr, PaCO2 increases. We conclude that the isocapnic hyperpnea associated with inhalation of CO2 in chickens is a CO2-coupled phenomenon and that it is mediated by CO2-sensitive intrapulmonary chemoreceptors.", "contents": "Regulation of arterial PCO2 during inhalation of CO2 in chickens. Since CO2-sensitive intrapulmonary chemoreceptors have been shown to exist in the avian lung, we conducted a series of experiments to determine if birds could regulate PaCO2 when confronted with an inspired CO2 load. Chickens were anesthetized with either pentobarbital (30 mg.kg-1) or phenobarbital (160 mg.kg-1). The PICO2 was either increased or decreased in successive 7 torr steps between 0 and 35 torr. At each level of PICO2, steady-state measurements of PaCO2, PaO2 and [H+]a were made. In three of ten experiments, tidal volume and respiratory frequency were determined and minute ventilation calculated. Our results indicate that as PICO2 is varied between 0 and 21 torr, minute ventilation increases and arterial homeostasis of PCO2 and [H+] is maintained; as the PICO2 is increased above 21 torr, PaCO2 increases. We conclude that the isocapnic hyperpnea associated with inhalation of CO2 in chickens is a CO2-coupled phenomenon and that it is mediated by CO2-sensitive intrapulmonary chemoreceptors."}
{"id": "PMID:24870", "title": "The transduction properties of tracheal stretch receptors in vitro.", "content": "Extrathoracic tracheal stretch receptors and tracheal tension were recorded in vitro when the trachea was stretched. The receptors responded to an increase in tension produced by displacement in the longitudinal or transverse axis of the trachea. They were sensitive to the rate of change of tension as well as the tension level itself, i.e. there was a dynamic component in the response. A fall in temperature decreased discharge frequency but the receptors were not affected by changes in PCO2 and pH of the perfusion fluid. Contraction of tracheal muscle, induced by acetylcholine, increased discharge frequency showing that the receptors studied were effectively in series with the muscle.", "contents": "The transduction properties of tracheal stretch receptors in vitro. Extrathoracic tracheal stretch receptors and tracheal tension were recorded in vitro when the trachea was stretched. The receptors responded to an increase in tension produced by displacement in the longitudinal or transverse axis of the trachea. They were sensitive to the rate of change of tension as well as the tension level itself, i.e. there was a dynamic component in the response. A fall in temperature decreased discharge frequency but the receptors were not affected by changes in PCO2 and pH of the perfusion fluid. Contraction of tracheal muscle, induced by acetylcholine, increased discharge frequency showing that the receptors studied were effectively in series with the muscle."}
{"id": "PMID:24889", "title": "Calcium-stimulated ATPase activity in homogenates of the secretory enamel organ in the rat.", "content": "The activity of calcium-stimulated ATPase (E.C. 3.6.1.3) in homogenates of the secretory enamel organ of rat incisors was studied biochemically. ATP hydrolysis was estimated from the amount of inorganic phosphate liberated. An analysis of the total degradation of ATP was initially performed to ensure that the enzyme assays pertained to the original substrate, ATP, and were not influenced by reaction products formed. Standard incubations were run in tris-maleate buffer, pH 8.2, with 3 mM ATP, 3 mM Ca2+ and 0.5 mM R 8231 at 37 degrees C. The presence of R 8231 was necessary to inhibit nonspecific alkaline phosphatase. The calcium-stimulated ATPase was completely inhibited when heated at 55-60 degrees C for 5 min. The pH optimum was found to be 8.2. The hydrolysis was substantially dependent on Ca2+ and was fastest when the ATP:Ca2+ ratio was 1:1. High substrate concentrations inhibited the hydrolysis. The addition of 1 mM Zn2+ and Ni2+ to the incubation medium markedly inhibited the hydrolysis as did, though less strongly, p-hydroxymercuribenzoate, oligomycin, EDTA and ruthenium red. l-Cysteine, mercaptoethanol, iodoacetic acid and sodium azide were without effect. F- was without effect unless added to a final concentration above 15 mM to media where Ca2+ had first been allowed to react with ATP.", "contents": "Calcium-stimulated ATPase activity in homogenates of the secretory enamel organ in the rat. The activity of calcium-stimulated ATPase (E.C. 3.6.1.3) in homogenates of the secretory enamel organ of rat incisors was studied biochemically. ATP hydrolysis was estimated from the amount of inorganic phosphate liberated. An analysis of the total degradation of ATP was initially performed to ensure that the enzyme assays pertained to the original substrate, ATP, and were not influenced by reaction products formed. Standard incubations were run in tris-maleate buffer, pH 8.2, with 3 mM ATP, 3 mM Ca2+ and 0.5 mM R 8231 at 37 degrees C. The presence of R 8231 was necessary to inhibit nonspecific alkaline phosphatase. The calcium-stimulated ATPase was completely inhibited when heated at 55-60 degrees C for 5 min. The pH optimum was found to be 8.2. The hydrolysis was substantially dependent on Ca2+ and was fastest when the ATP:Ca2+ ratio was 1:1. High substrate concentrations inhibited the hydrolysis. The addition of 1 mM Zn2+ and Ni2+ to the incubation medium markedly inhibited the hydrolysis as did, though less strongly, p-hydroxymercuribenzoate, oligomycin, EDTA and ruthenium red. l-Cysteine, mercaptoethanol, iodoacetic acid and sodium azide were without effect. F- was without effect unless added to a final concentration above 15 mM to media where Ca2+ had first been allowed to react with ATP."}
{"id": "PMID:24890", "title": "Demonstration of a K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity in enamel-and dentin-forming tissues in the rat.", "content": "p-Nitrophenyl phosphate hydrolysis was studied at neutral pH with tissue preparations of the rat secretory and maturation enamel organs and dental pulp. By introduction of inhibitors to nonspecific alkaline phosphatase activity and stimulants to the K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity, the latter enzyme activity could be demonstrated. This enzyme activity is generally held to be representative of the enzyme sodium- and potassium-stimulated adenosine triphosphatase. The K+-stimulated activity was magnesium dependent and highly sensitive to fluoride. It was inhibited completely by 3 mM fluoride in the incubation medium and about 1 mM produced half the maximum inhibition. The K+-independent enzyme activity was inhibited 50-60% by fluoride in concentrations between 3 and 15 mM. The high fluoride sensitivity of the K+-stimulated activity may perhaps help to explain the vulnerability of dental tissues to fluoride.", "contents": "Demonstration of a K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity in enamel-and dentin-forming tissues in the rat. p-Nitrophenyl phosphate hydrolysis was studied at neutral pH with tissue preparations of the rat secretory and maturation enamel organs and dental pulp. By introduction of inhibitors to nonspecific alkaline phosphatase activity and stimulants to the K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity, the latter enzyme activity could be demonstrated. This enzyme activity is generally held to be representative of the enzyme sodium- and potassium-stimulated adenosine triphosphatase. The K+-stimulated activity was magnesium dependent and highly sensitive to fluoride. It was inhibited completely by 3 mM fluoride in the incubation medium and about 1 mM produced half the maximum inhibition. The K+-independent enzyme activity was inhibited 50-60% by fluoride in concentrations between 3 and 15 mM. The high fluoride sensitivity of the K+-stimulated activity may perhaps help to explain the vulnerability of dental tissues to fluoride."}
{"id": "PMID:24894", "title": "Bicarbonate ion transport: a mechanism for the acidification of urine in the turtle.", "content": "The uricotelic turtle Pseudemys scripta acidifies the urine to a pH as low as 4 in the urinary bladder. Data in this report show that the mechanism of acidification in this bladder is the transport of bicarbonate ion from lumen to serosa, and that the temperature to which the turtles are adapted prior to the in vitro experiment largely determines the direction of the transmural carbon dioxide gradient observed. This temperature effect also serves to reconcile apparently disparate data that were previously reported. A new technique for the direct determination of the partial pressure of carbon dioxide was employed.", "contents": "Bicarbonate ion transport: a mechanism for the acidification of urine in the turtle. The uricotelic turtle Pseudemys scripta acidifies the urine to a pH as low as 4 in the urinary bladder. Data in this report show that the mechanism of acidification in this bladder is the transport of bicarbonate ion from lumen to serosa, and that the temperature to which the turtles are adapted prior to the in vitro experiment largely determines the direction of the transmural carbon dioxide gradient observed. This temperature effect also serves to reconcile apparently disparate data that were previously reported. A new technique for the direct determination of the partial pressure of carbon dioxide was employed."}
{"id": "PMID:24895", "title": "Oral cocaine: plasma concentrations and central effects.", "content": "Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally. Cocaine is not detected in the plasma until 30 minutes after oral administration, but peak plasma concentrations are similar after both routes. The subjective \"highs\" in man are greater after oral than after intranasal administration.", "contents": "Oral cocaine: plasma concentrations and central effects. Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally. Cocaine is not detected in the plasma until 30 minutes after oral administration, but peak plasma concentrations are similar after both routes. The subjective \"highs\" in man are greater after oral than after intranasal administration."}
{"id": "PMID:24896", "title": "MEN type IIa syndrome: dilemmas in modern management.", "content": "With the use of newer techniques, the multiple endocrine neoplasm II-A syndrome can now be diagnosed early in its evolution. This article discusses the clinical course of the syndrome, the diagnostic modalities employed, and the therapeutic interventions required. An approach to the individual patient with this syndrome is presented.", "contents": "MEN type IIa syndrome: dilemmas in modern management. With the use of newer techniques, the multiple endocrine neoplasm II-A syndrome can now be diagnosed early in its evolution. This article discusses the clinical course of the syndrome, the diagnostic modalities employed, and the therapeutic interventions required. An approach to the individual patient with this syndrome is presented."}
{"id": "PMID:24898", "title": "Muscle perfusion and the healing of below knee amputations.", "content": "Muscle pH has been used to assess the perfusion of the muscles at the site of below knee amputation in 20 patients having ischemia at the periphery. The results show that a muscle pH above 7.0 did not correlate with the outcome of amputation but that, when the pH was below 7.00, healing was never achieved.", "contents": "Muscle perfusion and the healing of below knee amputations. Muscle pH has been used to assess the perfusion of the muscles at the site of below knee amputation in 20 patients having ischemia at the periphery. The results show that a muscle pH above 7.0 did not correlate with the outcome of amputation but that, when the pH was below 7.00, healing was never achieved."}
{"id": "PMID:24899", "title": "The role of fibrin formation in the pathogenesis of bacteremic shock in the primate.", "content": "In this study, an attempt was made to elucidate further the role of intravascular fibrin formation in the pathogenesis of sepsis in the primate. It was found that injected live Escherichia coli caused death in primates within four to 11 hours as a result of microcirculatory failure and acidosis. Pretreatment with Arvin did not prolong the survival rate, probably because of an overloading of the reticuloendothelial system with fibrin degradation products. This study does not support an obligatory role for intravascular coagulation or fibrin formation in primate sepsis and coincides with an earlier report (6) from this laboratory on cats. Vascular damage and malfunction, secondary to mediators released by platelets, leukocytes, red cells or Hageman factor, are not ruled out.", "contents": "The role of fibrin formation in the pathogenesis of bacteremic shock in the primate. In this study, an attempt was made to elucidate further the role of intravascular fibrin formation in the pathogenesis of sepsis in the primate. It was found that injected live Escherichia coli caused death in primates within four to 11 hours as a result of microcirculatory failure and acidosis. Pretreatment with Arvin did not prolong the survival rate, probably because of an overloading of the reticuloendothelial system with fibrin degradation products. This study does not support an obligatory role for intravascular coagulation or fibrin formation in primate sepsis and coincides with an earlier report (6) from this laboratory on cats. Vascular damage and malfunction, secondary to mediators released by platelets, leukocytes, red cells or Hageman factor, are not ruled out."}
{"id": "PMID:24901", "title": "Training and use of surgeon's assistants.", "content": "\"Physician extenders\" of various types have been produced in the past few years. The University of Alabama in Birmingham has trained surgeon's assistants over the past 9 years, graduating 53 individuals after a 2-year course of didactic, laboratory, and clinical instruction. The graduates have performed satisfactorily, working with surgeons in the community setting and as part of highly specialized teams in large medical centers. One third work in general surgery, one third in cardiovascular thoracic surgery, and one third in other special areas. The authors conclude that these individuals will play an increasing role in allowing surgical therapy to be delivered in an efficient and effective manner.", "contents": "Training and use of surgeon's assistants. \"Physician extenders\" of various types have been produced in the past few years. The University of Alabama in Birmingham has trained surgeon's assistants over the past 9 years, graduating 53 individuals after a 2-year course of didactic, laboratory, and clinical instruction. The graduates have performed satisfactorily, working with surgeons in the community setting and as part of highly specialized teams in large medical centers. One third work in general surgery, one third in cardiovascular thoracic surgery, and one third in other special areas. The authors conclude that these individuals will play an increasing role in allowing surgical therapy to be delivered in an efficient and effective manner."}
{"id": "PMID:24902", "title": "Droperidol, its alpha-adrenergic blocking action on the aortic strip and inhibitory action on norepinephrine uptake of the adrenergic terminal of the left atrial strip of rabbit.", "content": "In aortic strips, the dose-response curves for phenylephrine were obtained before and after addition of droperidol. Droperidol caused a parallel shift of the curves dose-dependently toward the right side and its grade of the shift was greater than caused by phentolamine at the same concentration. In the left atrial strip, the potentiation of contraction by tyramine was markedly depressed by droperidol. In the reserpinized preparation, the effect of tyramine was depressed markedly and there was no norepinephrine fluorescence. After incubation with norepinephrine they were restored to the same level as in non-reserpinized preparations. However, incubation with droperidol before norepinephrine blocked the restoration. It is postulated that droperidol may have both alpha-adrenergic blocking action and inhibitory action on norepinephrine uptake by adrenergic terminals.", "contents": "Droperidol, its alpha-adrenergic blocking action on the aortic strip and inhibitory action on norepinephrine uptake of the adrenergic terminal of the left atrial strip of rabbit. In aortic strips, the dose-response curves for phenylephrine were obtained before and after addition of droperidol. Droperidol caused a parallel shift of the curves dose-dependently toward the right side and its grade of the shift was greater than caused by phentolamine at the same concentration. In the left atrial strip, the potentiation of contraction by tyramine was markedly depressed by droperidol. In the reserpinized preparation, the effect of tyramine was depressed markedly and there was no norepinephrine fluorescence. After incubation with norepinephrine they were restored to the same level as in non-reserpinized preparations. However, incubation with droperidol before norepinephrine blocked the restoration. It is postulated that droperidol may have both alpha-adrenergic blocking action and inhibitory action on norepinephrine uptake by adrenergic terminals."}
{"id": "PMID:24911", "title": "The mechanism of urinary continence after prostatectomy.", "content": "An anatomical and neuropharmacological study of the urethra was performed in 19 patients after prostatetectomy to investigate the mechanism of continence. Anatomically, the urethral segment responsible for the postprostatectomy continence was located distal to the open prostatic fossa in the external sphincter which is comprised of intrinsic striated muscle and is called arbitrarily rhabdosphincter by the author. This unique striated muscle in the rhabdosphinecter appears to be primarily under the alpha-adrenergic influence in view of the change in the urethral pressure profile observed following alpha-adrenergic drugs.", "contents": "The mechanism of urinary continence after prostatectomy. An anatomical and neuropharmacological study of the urethra was performed in 19 patients after prostatetectomy to investigate the mechanism of continence. Anatomically, the urethral segment responsible for the postprostatectomy continence was located distal to the open prostatic fossa in the external sphincter which is comprised of intrinsic striated muscle and is called arbitrarily rhabdosphincter by the author. This unique striated muscle in the rhabdosphinecter appears to be primarily under the alpha-adrenergic influence in view of the change in the urethral pressure profile observed following alpha-adrenergic drugs."}
{"id": "PMID:24912", "title": "Pathology of germ cell tumors of the testis.", "content": "Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis.", "contents": "Pathology of germ cell tumors of the testis. Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis."}
{"id": "PMID:24915", "title": "Cytogenic studies of cryptorchid testes.", "content": "Twenty-nine patients with unilateral or bilateral cryptochism underwent biopsies of the testis at the time of orchiopexy. Karyotype evaluation of fibroblasts obtained from tissue cultures of the biopsy specimen was completed counting a minimum of twenty-five cells. In 1 patient with multiple anomalies a 46,XYDq+ karyotype was identified. All other karyotypes were normal suggesting cryptorchism is not associated with abnormal testicular cytogenetics.", "contents": "Cytogenic studies of cryptorchid testes. Twenty-nine patients with unilateral or bilateral cryptochism underwent biopsies of the testis at the time of orchiopexy. Karyotype evaluation of fibroblasts obtained from tissue cultures of the biopsy specimen was completed counting a minimum of twenty-five cells. In 1 patient with multiple anomalies a 46,XYDq+ karyotype was identified. All other karyotypes were normal suggesting cryptorchism is not associated with abnormal testicular cytogenetics."}
{"id": "PMID:24916", "title": "[Evaluation of metabolic profile tests using a computer].", "content": "A programme has been developed for the evaluation of metabolism profile tests in dairy cows by means of the TESLA-200 computer in the FORTRAN language. The computer evaluates and plots the metabolism profile from input data punched on tape in the IBM code by the Consul-253 electronic organization automatic device. The metabolism profile is represented as a column graph (histogram), the levels of individual parameters being confronted with the reference levels with a 95% confidence interval and the deviations are expressed in units defined as 1/2 of the confidence interval for each parameter. Calculation by this procedure enables the construction of a profile record in which any step beyond the 95% confidence interval in any parameters is seen very clearly. The computer also produces a table of exactly calculated values of deviations from the reference levels and makes it possible to determine the numbers of abnormalities for individual parameters in the animals tested.", "contents": "[Evaluation of metabolic profile tests using a computer]. A programme has been developed for the evaluation of metabolism profile tests in dairy cows by means of the TESLA-200 computer in the FORTRAN language. The computer evaluates and plots the metabolism profile from input data punched on tape in the IBM code by the Consul-253 electronic organization automatic device. The metabolism profile is represented as a column graph (histogram), the levels of individual parameters being confronted with the reference levels with a 95% confidence interval and the deviations are expressed in units defined as 1/2 of the confidence interval for each parameter. Calculation by this procedure enables the construction of a profile record in which any step beyond the 95% confidence interval in any parameters is seen very clearly. The computer also produces a table of exactly calculated values of deviations from the reference levels and makes it possible to determine the numbers of abnormalities for individual parameters in the animals tested."}
{"id": "PMID:24917", "title": "[Intensity of acid-base reactions of the blood and cerebrospinal fluid in sheep after intraluminal stress induced by urea and acetic acid].", "content": "Acid-base indices of the blood and cerebro-spinal fluid were studied on Astrup apparatus (BMS 2) in an experiment with twelve, two- to three-year-old Merino sheep, being in the first half of the gravidity period, under clinical conditions after the administration of 0.8 g urea per 1 kg live weight followed by, in half an hour, the administration of acetic acid (8% vinegar, a dose of 2 ml per 1 kg live weight). Heparinized syringes were used to take blood samples anaerobically before the beginning of the experiment, then after 15, 30, 45, 60, 75, 90, 105, 120 minutes and after 4 and 24 hours. The fluid was taken by heparinized capillaries before the beginning of the experiment, then after 30, 60, 90 and 120 minutes and after 4 and 24 hours. The following indices were obtained, and/or calculated from nomographs: actual pH, carbon dioxide pressure--pCO2, base excess--BE, buffer bases--BB, standard and actual bicarbonate--SB, AB, total carbon dioxide--tCO2. After 15 minutes' interval since the administration of urea significant changes in the values of the indices, especially higher pH values and paradoxical pCO2 drop, were recorded. After the administration of acetic acid overcompensated acidosis of the organism occurred (accompanied even by mortality of the experimental sheep). Towards the end of the experiments the results illustrated basemia. A depressing effect of the lower pH on the toxicity of ammonia was also confirmed. The reaction of the fluid to the urea and acetic acid stress opposite to the venous blood was retarded and the values of the indices studied showed some variability.", "contents": "[Intensity of acid-base reactions of the blood and cerebrospinal fluid in sheep after intraluminal stress induced by urea and acetic acid]. Acid-base indices of the blood and cerebro-spinal fluid were studied on Astrup apparatus (BMS 2) in an experiment with twelve, two- to three-year-old Merino sheep, being in the first half of the gravidity period, under clinical conditions after the administration of 0.8 g urea per 1 kg live weight followed by, in half an hour, the administration of acetic acid (8% vinegar, a dose of 2 ml per 1 kg live weight). Heparinized syringes were used to take blood samples anaerobically before the beginning of the experiment, then after 15, 30, 45, 60, 75, 90, 105, 120 minutes and after 4 and 24 hours. The fluid was taken by heparinized capillaries before the beginning of the experiment, then after 30, 60, 90 and 120 minutes and after 4 and 24 hours. The following indices were obtained, and/or calculated from nomographs: actual pH, carbon dioxide pressure--pCO2, base excess--BE, buffer bases--BB, standard and actual bicarbonate--SB, AB, total carbon dioxide--tCO2. After 15 minutes' interval since the administration of urea significant changes in the values of the indices, especially higher pH values and paradoxical pCO2 drop, were recorded. After the administration of acetic acid overcompensated acidosis of the organism occurred (accompanied even by mortality of the experimental sheep). Towards the end of the experiments the results illustrated basemia. A depressing effect of the lower pH on the toxicity of ammonia was also confirmed. The reaction of the fluid to the urea and acetic acid stress opposite to the venous blood was retarded and the values of the indices studied showed some variability."}
{"id": "PMID:24918", "title": "Polypoid nonchromaffin paraganglioma of the duodenum.", "content": "A polypoid tumor was surgically removed from the second part of the duodenum of a 56-year-old male. The main body consisted of large epithelioid cells arranged in an adenoma like pattern of strands and nests. These cells were argyrophil and had marked nonspecific esterase activity. Unmyelinated nerves with proliferated Schwann cells accompanied these epithelioid cells together with scattered gangliocyte like elements. Ultramicroscopically, the epithelioid cells were seen to contain round electron dense granules, 150 nm in diameter on average. The tumor is considered to be a nonchromaffin paraganglioma, as it probable developed from paraganglion cells associated with small arteries or branches of the vagus nerve, or from the undifferentiated pluripotent APUD cells of the duodenum.", "contents": "Polypoid nonchromaffin paraganglioma of the duodenum. A polypoid tumor was surgically removed from the second part of the duodenum of a 56-year-old male. The main body consisted of large epithelioid cells arranged in an adenoma like pattern of strands and nests. These cells were argyrophil and had marked nonspecific esterase activity. Unmyelinated nerves with proliferated Schwann cells accompanied these epithelioid cells together with scattered gangliocyte like elements. Ultramicroscopically, the epithelioid cells were seen to contain round electron dense granules, 150 nm in diameter on average. The tumor is considered to be a nonchromaffin paraganglioma, as it probable developed from paraganglion cells associated with small arteries or branches of the vagus nerve, or from the undifferentiated pluripotent APUD cells of the duodenum."}
{"id": "PMID:24919", "title": "[Artificial arterial hypotension during surgical treatment of intracranial aneurysms].", "content": "In studying the content of lactic and pyruvic acids in the cerebrospinal fluid of 31 patients during operation for intracranial aneurysms under halothane anesthesia, the authors established that the performance of these operations under protection of deep (40 mm Hg) and prolonged (up to 2 hrs 25 min) artificial arterial hypotension in an uncomplicated course of the surgical intervention was not attended with hypoxic damage of the brain. The danger of hypoxia developing became greater when acute disturbances of blood flow in the cerebral arteries (clipping of a vessel, spasm) occurred in the period of hypotension.", "contents": "[Artificial arterial hypotension during surgical treatment of intracranial aneurysms]. In studying the content of lactic and pyruvic acids in the cerebrospinal fluid of 31 patients during operation for intracranial aneurysms under halothane anesthesia, the authors established that the performance of these operations under protection of deep (40 mm Hg) and prolonged (up to 2 hrs 25 min) artificial arterial hypotension in an uncomplicated course of the surgical intervention was not attended with hypoxic damage of the brain. The danger of hypoxia developing became greater when acute disturbances of blood flow in the cerebral arteries (clipping of a vessel, spasm) occurred in the period of hypotension."}
{"id": "PMID:24923", "title": "Dehydrogenation of indanol by rabbit liver 3-hydroxyhexobarbital dehydrogenase.", "content": "1. Among the several enzyme activities in rabbit liver cytosol able to dehydrogenate 1-indanol, only the main activity was not separable from 3-hydroxyhexobarbital dehydrogenase during purification including polyacrylamide gel disc electrophoresis. 2. Results of mixed substrate method indicated that the same enzyme catalyses the dehydrogenation of 1-indanol and 3-hydroxyhexobarbital. The ratio between the two dehydrogenation activities was almost constant as the enzyme underwent thermal inactivation. The Ki values of p-chloromercuribenzoate, the Km values for NAD+, and the Km values for NADP+ were very similar for the two dehydrogenations. These results lead to the conclusion that the same enzyme catalyses the dehydrogenation of 3-hydroxyhexobarbital and 1-indanol. 3. 1-Tetralol, 1-acenaphthenol, 9-fluorenol, thiochroman-4-ol and 4-chromanol also served as substrate of the enzyme, but 2-indanol, 2-tetralol, and trans- and cis-indan-1,2-diol were not oxidized. 4. Reversibility of the reaction was also confirmed using 1-indanone as substrate.", "contents": "Dehydrogenation of indanol by rabbit liver 3-hydroxyhexobarbital dehydrogenase. 1. Among the several enzyme activities in rabbit liver cytosol able to dehydrogenate 1-indanol, only the main activity was not separable from 3-hydroxyhexobarbital dehydrogenase during purification including polyacrylamide gel disc electrophoresis. 2. Results of mixed substrate method indicated that the same enzyme catalyses the dehydrogenation of 1-indanol and 3-hydroxyhexobarbital. The ratio between the two dehydrogenation activities was almost constant as the enzyme underwent thermal inactivation. The Ki values of p-chloromercuribenzoate, the Km values for NAD+, and the Km values for NADP+ were very similar for the two dehydrogenations. These results lead to the conclusion that the same enzyme catalyses the dehydrogenation of 3-hydroxyhexobarbital and 1-indanol. 3. 1-Tetralol, 1-acenaphthenol, 9-fluorenol, thiochroman-4-ol and 4-chromanol also served as substrate of the enzyme, but 2-indanol, 2-tetralol, and trans- and cis-indan-1,2-diol were not oxidized. 4. Reversibility of the reaction was also confirmed using 1-indanone as substrate."}
{"id": "PMID:24924", "title": "[Anabolic and catabolic enzymes of urea metabolism in a carbohydrate-utilizing strain of Candida guilliermondii].", "content": "The yeast \"H\" of the genus Candida guilliermondii can grow on hydrocarbons as the only source for carbon. Urea can serve as a nitrogen source for this yeast which lacks detectable urease activity. During urea metabolism ammonia has never been accumulated in the culture medium. However, transferring the yeast from complete urea-medium into an urea containing phophate-buffer, the degradation of urea continues and ammonia is accumulated as well as CO2 evolved. In cell-free extracts of the yeast urea amidolyase activity was detected in the presence of ATP, biotin and specific cations. Obviously, the synthesis of urea amidolyase is induced by urea and arginine and repressed by the catabolite ammonia. Similarly the synthesis of arginase is regulated by arginine and ammonia. The analytical data of the arginase action differ significantly in relation to the carbon source of the culture medium. Both the level of arginase and ornithine carbamyl-transferase change in a characteristic way during the batch-culture. From the lower level of arginase in relation to ornithine carbamyltransferase it can be concluded that especially in alkane-metabolizing yeast the arginine catabolism is not very intensive.", "contents": "[Anabolic and catabolic enzymes of urea metabolism in a carbohydrate-utilizing strain of Candida guilliermondii]. The yeast \"H\" of the genus Candida guilliermondii can grow on hydrocarbons as the only source for carbon. Urea can serve as a nitrogen source for this yeast which lacks detectable urease activity. During urea metabolism ammonia has never been accumulated in the culture medium. However, transferring the yeast from complete urea-medium into an urea containing phophate-buffer, the degradation of urea continues and ammonia is accumulated as well as CO2 evolved. In cell-free extracts of the yeast urea amidolyase activity was detected in the presence of ATP, biotin and specific cations. Obviously, the synthesis of urea amidolyase is induced by urea and arginine and repressed by the catabolite ammonia. Similarly the synthesis of arginase is regulated by arginine and ammonia. The analytical data of the arginase action differ significantly in relation to the carbon source of the culture medium. Both the level of arginase and ornithine carbamyl-transferase change in a characteristic way during the batch-culture. From the lower level of arginase in relation to ornithine carbamyltransferase it can be concluded that especially in alkane-metabolizing yeast the arginine catabolism is not very intensive."}
{"id": "PMID:24925", "title": "[On molecular biology of aging. 11th communication. Enzyme adaptation, age (author's transl)].", "content": "Age-dependent modifications of enzyme adaptations in response to a variety of environmental alterations are a biochemical expression of biological ageing. In this paper age-dependent changes of the adaptation of a number of enzymes are described. Experiments from our laboratory indicate that pyruvate kinase is more responsive to starvation and refeeding in young animals. The diminished response of pyruvate kinase in old age is caused by a decreased adaptability of the regulatory isoenzyme PK-L.", "contents": "[On molecular biology of aging. 11th communication. Enzyme adaptation, age (author's transl)]. Age-dependent modifications of enzyme adaptations in response to a variety of environmental alterations are a biochemical expression of biological ageing. In this paper age-dependent changes of the adaptation of a number of enzymes are described. Experiments from our laboratory indicate that pyruvate kinase is more responsive to starvation and refeeding in young animals. The diminished response of pyruvate kinase in old age is caused by a decreased adaptability of the regulatory isoenzyme PK-L."}
{"id": "PMID:24961", "title": "Effect of lime-pelleting on nodulation and yield of soybean grown in acid soil.", "content": "An experiment for studying the effect of lime-pelleting of inoculated seed of soybean [Glycine max. (L.) Merr.] on nodulation, growth, and grain yield was undertaken in red sandy loam of Bangalore, having a pH of 4.0. The results indicated that inoculation alone increased significantly nodulation, plant dry weight, and grain yield. But inoculation plus lime-pelleting significantly increased the dry weight of nodules and plants, but not the grain yield. However, lime-pelleting was found to be beneficial though not essential in acid soils.", "contents": "Effect of lime-pelleting on nodulation and yield of soybean grown in acid soil. An experiment for studying the effect of lime-pelleting of inoculated seed of soybean [Glycine max. (L.) Merr.] on nodulation, growth, and grain yield was undertaken in red sandy loam of Bangalore, having a pH of 4.0. The results indicated that inoculation alone increased significantly nodulation, plant dry weight, and grain yield. But inoculation plus lime-pelleting significantly increased the dry weight of nodules and plants, but not the grain yield. However, lime-pelleting was found to be beneficial though not essential in acid soils."}
{"id": "PMID:24962", "title": "[Application of a TRICIN-buffered modification of the CMRL-1969 medium in cell and virus cultivation (author's transl)].", "content": "CMRL-1969 medium (Healy et al., 1971) was modified by using 0.02 molar N-[Tris-(hydroxymethyl)-methyl]-glycin (= TRICIN) instead of bicarbonate as the buffer substance. Several permanent cell lines and primary cell cultures did not show growth differences in the two medium variants. Like other non volatile buffers TRICIN abolishes the initial increase of the Ph in freshly split or newly fed closed vessel cultures, but in 0.02 M concentration maintains the same buffering capacity of the medium as compared to bicarbonate. Multiplication of Entero-, Adeno-, Herpes-, Influenza-A-, and Vaccinia-viruses was also not altered. The medium allows open vessel methods like microtiter- and plaque-tests to be conducted under normal atmosphere and seems especially useful when initial pH-values are to be set in the rank of 7.5 to 8.6. For microtiter neutralization tests with enteroviruses a medium adjusted to pH 7.6 and a cell density of 10(5) cells/cm2 was found optimal. Plaque formation of Coxsackie-B-viruses reached a maximal plaque-size and -number when the pH of the double concentrated medium was beyond 8.2.", "contents": "[Application of a TRICIN-buffered modification of the CMRL-1969 medium in cell and virus cultivation (author's transl)]. CMRL-1969 medium (Healy et al., 1971) was modified by using 0.02 molar N-[Tris-(hydroxymethyl)-methyl]-glycin (= TRICIN) instead of bicarbonate as the buffer substance. Several permanent cell lines and primary cell cultures did not show growth differences in the two medium variants. Like other non volatile buffers TRICIN abolishes the initial increase of the Ph in freshly split or newly fed closed vessel cultures, but in 0.02 M concentration maintains the same buffering capacity of the medium as compared to bicarbonate. Multiplication of Entero-, Adeno-, Herpes-, Influenza-A-, and Vaccinia-viruses was also not altered. The medium allows open vessel methods like microtiter- and plaque-tests to be conducted under normal atmosphere and seems especially useful when initial pH-values are to be set in the rank of 7.5 to 8.6. For microtiter neutralization tests with enteroviruses a medium adjusted to pH 7.6 and a cell density of 10(5) cells/cm2 was found optimal. Plaque formation of Coxsackie-B-viruses reached a maximal plaque-size and -number when the pH of the double concentrated medium was beyond 8.2."}
{"id": "PMID:24963", "title": "Clotting and fibrinolytic activities of Bacteroides melaninogenicus.", "content": "106 strains of Bacteroides melaninogenicus ss. asaccharolyticus, intermedius and melaninogenicus were tested for production of extracellular blood clotting and fibrinolytic factors. 78.3% of tested strains caused clotting of rabbit plasma and 79.2% activated human plasminogen. Strains producing the clotting or fibrinolytic factor only were isolated. Both factors were quite active, as positive results for most strains were detected within one hour of incubation in controlled test system.", "contents": "Clotting and fibrinolytic activities of Bacteroides melaninogenicus. 106 strains of Bacteroides melaninogenicus ss. asaccharolyticus, intermedius and melaninogenicus were tested for production of extracellular blood clotting and fibrinolytic factors. 78.3% of tested strains caused clotting of rabbit plasma and 79.2% activated human plasminogen. Strains producing the clotting or fibrinolytic factor only were isolated. Both factors were quite active, as positive results for most strains were detected within one hour of incubation in controlled test system."}
{"id": "PMID:24964", "title": "Studies on antituberculotic action of some phenothiazine derivatives in vitro.", "content": "Five phenothiazine derivatives (chlorpromazine, levomepromazine, diethazine, promethazine and chlorpromazine) sulphoxyde were tested for antimycobacterial activity. The growth of Mycobacterium tuberculosis, M. bovis and M. butyricum was inhibited by chlorpromazine practically at identical concentrations. The minimum inhibitory concentrations for M. tuberculosis were: chlorpromazine and levomepromazine, 10 microgram/ml; diethazine and promethazine 20 microgram/ml, whilst chlorpromazine sulphoxyde was ineffective even at a concentration of 100 microgram/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on M. tuberculosis at 50 microgram/ml; total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 microgram/ml. Preliminary studies, in mouse experiments phenothiazine derivatives were ineffective.", "contents": "Studies on antituberculotic action of some phenothiazine derivatives in vitro. Five phenothiazine derivatives (chlorpromazine, levomepromazine, diethazine, promethazine and chlorpromazine) sulphoxyde were tested for antimycobacterial activity. The growth of Mycobacterium tuberculosis, M. bovis and M. butyricum was inhibited by chlorpromazine practically at identical concentrations. The minimum inhibitory concentrations for M. tuberculosis were: chlorpromazine and levomepromazine, 10 microgram/ml; diethazine and promethazine 20 microgram/ml, whilst chlorpromazine sulphoxyde was ineffective even at a concentration of 100 microgram/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on M. tuberculosis at 50 microgram/ml; total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 microgram/ml. Preliminary studies, in mouse experiments phenothiazine derivatives were ineffective."}
{"id": "PMID:24965", "title": "The nature of clotting and fibrinolytic activities of Bacteroids melaninogenicus.", "content": "From the supernatant of B. melaninogenicus ss. asaccharolyticus culture, a protein fraction was isolated by ethanol precipitation. The fraction was tested for the presence of clotting and fibrinolytic activities by application of quantitative techniques and specific substrates for measurement of prothrombin and plasminogen activation, and collagenase and elastase activity. It is postulated that ability of Bacteroides melaninogenicus ss. asaccharolyticus extracellular factors to clot fibrinogen and activate plasminogen, are due to a limited proteolysis by the proteolytic enzymes produced by this microorganism and not to the existence of specific B. melaninogenicus coagulase of plasminogen activator.", "contents": "The nature of clotting and fibrinolytic activities of Bacteroids melaninogenicus. From the supernatant of B. melaninogenicus ss. asaccharolyticus culture, a protein fraction was isolated by ethanol precipitation. The fraction was tested for the presence of clotting and fibrinolytic activities by application of quantitative techniques and specific substrates for measurement of prothrombin and plasminogen activation, and collagenase and elastase activity. It is postulated that ability of Bacteroides melaninogenicus ss. asaccharolyticus extracellular factors to clot fibrinogen and activate plasminogen, are due to a limited proteolysis by the proteolytic enzymes produced by this microorganism and not to the existence of specific B. melaninogenicus coagulase of plasminogen activator."}
{"id": "PMID:24966", "title": "[Microbial growth on an expansion joint of a reservoir for drinkingwater (author's transl)].", "content": "In a clear water reservoir built in ready construction after a working-period of five months quite a lot of slime could be found on the expansion joint filled with tightening compound on the base of Thiokol. The covering slime could be removed easily with a rubber-screen. The microbiological analysis showed an extremely high number of colonies and additional the slime was secondarily settled with Protozoa. An influence on the water in the reservoir could not be found out under working conditions.", "contents": "[Microbial growth on an expansion joint of a reservoir for drinkingwater (author's transl)]. In a clear water reservoir built in ready construction after a working-period of five months quite a lot of slime could be found on the expansion joint filled with tightening compound on the base of Thiokol. The covering slime could be removed easily with a rubber-screen. The microbiological analysis showed an extremely high number of colonies and additional the slime was secondarily settled with Protozoa. An influence on the water in the reservoir could not be found out under working conditions."}
{"id": "PMID:24967", "title": "[On the determination of chlorine with a polarographic probe. 2nd communication: experimental arrangement and results under application (author's transl)].", "content": "The examination of the physical properties of the instrument showed several possibilities of meter-error mainly due to constructive disadvantages. After having found this a special experimental arrangement was worked out to exclude errors. Then good linear correlations of the meter-reading and the analytical DPD-Method for free Chlorine were found for pH-values ranging from 3.7 to 11. Further the results of a test under practical conditions in a swimming pool are shown and the possibility to discriminate different types of waters by their chlorine demand under constant-titration.", "contents": "[On the determination of chlorine with a polarographic probe. 2nd communication: experimental arrangement and results under application (author's transl)]. The examination of the physical properties of the instrument showed several possibilities of meter-error mainly due to constructive disadvantages. After having found this a special experimental arrangement was worked out to exclude errors. Then good linear correlations of the meter-reading and the analytical DPD-Method for free Chlorine were found for pH-values ranging from 3.7 to 11. Further the results of a test under practical conditions in a swimming pool are shown and the possibility to discriminate different types of waters by their chlorine demand under constant-titration."}
{"id": "PMID:24968", "title": "[Acid-base equilibrium in patients with tick-borne encephalitis and similar diseases].", "content": "The study is concerned with the acid-base balance in 92 patients with tick-borne encephalitis, tick-borne fever and meningitis of an obscure etiology. In many cases there was a shift in the direction of a metabolic acidosis, which was most vividly expressed in the meningitic form of tick-borne encephalitis. Some of the patients were treated by sodium bicarbonate which exerted a positive effect. The degree of changed indices of the acid-base balance and the time of their appearance helps in the diagnosis of tick-borne encephalitis correct evaluation of the severity of the condition and timely prescription of correction therapy.", "contents": "[Acid-base equilibrium in patients with tick-borne encephalitis and similar diseases]. The study is concerned with the acid-base balance in 92 patients with tick-borne encephalitis, tick-borne fever and meningitis of an obscure etiology. In many cases there was a shift in the direction of a metabolic acidosis, which was most vividly expressed in the meningitic form of tick-borne encephalitis. Some of the patients were treated by sodium bicarbonate which exerted a positive effect. The degree of changed indices of the acid-base balance and the time of their appearance helps in the diagnosis of tick-borne encephalitis correct evaluation of the severity of the condition and timely prescription of correction therapy."}
{"id": "PMID:24969", "title": "[Use of neuroleptics for the treatment of chronic alcoholism (psychopathology of the attraction to alcohol)].", "content": "A psychopathological analysis of alcoholic drives in patients with alcoholism demonstrates that along with well-known negative symptoms of an alcoholic mental defect there is a productive psychopathological symptom in the clinical picture as well. Having this view, the author in 148 cases of alcoholism applied etoperasine (trilafon), and neuleptil (propericiasin)--neuroleptical drugs, possessing antipsychotic properties and relatively not toxic. As a result there was a distinct and rapid inhibition of pathological drives to alcohol with a good tolerance to the preparations. The use of these drugs activates the role of the patient in the process of treatment, increases the effectiveness of psychotherapy, and is technically simple in use. They may be prescribed for the prevention of relapses, arrest of bouts when other methods are ineffective.", "contents": "[Use of neuroleptics for the treatment of chronic alcoholism (psychopathology of the attraction to alcohol)]. A psychopathological analysis of alcoholic drives in patients with alcoholism demonstrates that along with well-known negative symptoms of an alcoholic mental defect there is a productive psychopathological symptom in the clinical picture as well. Having this view, the author in 148 cases of alcoholism applied etoperasine (trilafon), and neuleptil (propericiasin)--neuroleptical drugs, possessing antipsychotic properties and relatively not toxic. As a result there was a distinct and rapid inhibition of pathological drives to alcohol with a good tolerance to the preparations. The use of these drugs activates the role of the patient in the process of treatment, increases the effectiveness of psychotherapy, and is technically simple in use. They may be prescribed for the prevention of relapses, arrest of bouts when other methods are ineffective."}
{"id": "PMID:24970", "title": "Effect of extracellular pH and inhibitors on the gluconeogenesis and ammoniagenesis relationship in rat kidney cortex slices.", "content": "1. Gluconeogenesis from glutamine, fumarate, pyruvate, glutamine plus fumarate, and glutamine plus pyruvate, was generally higher at pH 7.1 than at pH 7.4 and 7.7, whereas ammoniagenesis did not depend on the pH of the medium. 2. The intermediates of the Krebs cycle decreased ammonia formation from glutamine, raising at the same time gluconeogenesis. 3. Arsenite, malonate, maleate, hydrazine and 2,4-dinitrophenol inhibited gluconeogenesis, and enhanced simultaneously ammonia formation irrespective of the pH of the medium.", "contents": "Effect of extracellular pH and inhibitors on the gluconeogenesis and ammoniagenesis relationship in rat kidney cortex slices. 1. Gluconeogenesis from glutamine, fumarate, pyruvate, glutamine plus fumarate, and glutamine plus pyruvate, was generally higher at pH 7.1 than at pH 7.4 and 7.7, whereas ammoniagenesis did not depend on the pH of the medium. 2. The intermediates of the Krebs cycle decreased ammonia formation from glutamine, raising at the same time gluconeogenesis. 3. Arsenite, malonate, maleate, hydrazine and 2,4-dinitrophenol inhibited gluconeogenesis, and enhanced simultaneously ammonia formation irrespective of the pH of the medium."}
{"id": "PMID:24978", "title": "Neuroleptic blockade of the effect of various neurotransmitter substances.", "content": "The antagonistic effect of neuroleptics to acetylcholine, histamine, 5-HT, and noradrenaline was examined in various in vivo and in vitro models. Piflutixol, a new potent thioxanthene neuroleptic, markedly antagonizes the effect of dopamine, noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Clozapine and chlorprothixene on the other hand, have high affinity for muscarinic receptors and also antagonize the effect of histamine and 5-HT, whereas clozapine was a weak antagonist of noradrenaline and dopamine when compared to the effect of piflutixol. Chlorprothixene, however, also exhibits a rather good antagonism of noradrenaline and dopamine. Haloperidol proved to be weak in all models when compared with the other neuroleptics examined. Flupenthixol specifically antagonizes dopamine and noradrenaline, whereas fluphenazine was a more potent antagonist of dopamine than of the other transmitters. The data show, that neuroleptic compounds possess very different profiles with regard to interaction with various neurotransmitter substances. It is suggested, that the rather potent anti 5-HT and antihistamine effects observed for certain substances may contribute to the central effect of these drugs.", "contents": "Neuroleptic blockade of the effect of various neurotransmitter substances. The antagonistic effect of neuroleptics to acetylcholine, histamine, 5-HT, and noradrenaline was examined in various in vivo and in vitro models. Piflutixol, a new potent thioxanthene neuroleptic, markedly antagonizes the effect of dopamine, noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Clozapine and chlorprothixene on the other hand, have high affinity for muscarinic receptors and also antagonize the effect of histamine and 5-HT, whereas clozapine was a weak antagonist of noradrenaline and dopamine when compared to the effect of piflutixol. Chlorprothixene, however, also exhibits a rather good antagonism of noradrenaline and dopamine. Haloperidol proved to be weak in all models when compared with the other neuroleptics examined. Flupenthixol specifically antagonizes dopamine and noradrenaline, whereas fluphenazine was a more potent antagonist of dopamine than of the other transmitters. The data show, that neuroleptic compounds possess very different profiles with regard to interaction with various neurotransmitter substances. It is suggested, that the rather potent anti 5-HT and antihistamine effects observed for certain substances may contribute to the central effect of these drugs."}
{"id": "PMID:24980", "title": "Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients.", "content": "Efficacy and side effects of flurazepam 15 mg, fosazepam 60 mg, and nitrazepam 5 mg were studied in 17 psychogeriatric patients. The drugs were equipotent in maintaining sleep but nitrazepam had more side effects than the other hypnotics, and it induced a rebound insomnia after withdrawal. All hypnotics lost some of their efficacy towards the end of 7 days' administration. Patients with evident cerebrovascular disease were vulnerable to the side effects of the benzodiazepine hypnotics. The side effects did not correlate with the age of a patient. In addition, no correlations were found between the serum levels of fosazepam or its main metabolite and the side effects.", "contents": "Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients. Efficacy and side effects of flurazepam 15 mg, fosazepam 60 mg, and nitrazepam 5 mg were studied in 17 psychogeriatric patients. The drugs were equipotent in maintaining sleep but nitrazepam had more side effects than the other hypnotics, and it induced a rebound insomnia after withdrawal. All hypnotics lost some of their efficacy towards the end of 7 days' administration. Patients with evident cerebrovascular disease were vulnerable to the side effects of the benzodiazepine hypnotics. The side effects did not correlate with the age of a patient. In addition, no correlations were found between the serum levels of fosazepam or its main metabolite and the side effects."}
{"id": "PMID:24981", "title": "Three years' maintenance neuroleptic treatment in schizophrenia--before and beyond.", "content": "A group of patients with schizophrenia, initially 67 patients, was studied over a period of 3 years. After three years 36 out of 67 patients were still on the same depot neuroleptic. The main aim was to describe and compare maintenance neuroleptic therapy using two depot neuroleptics, fluphenazine decanoate and pipotiazine palmitate, given monthly. Before the outpatient care the patients had participated in the department's comprehensive hospital treatment including depot neuroleptic medication. After a 1-year clinical trial with frequent assessments of the patients, significant symptom reductions were found on all rating scales. During the last 2 years of the study only drug therapy was given. Improvement concerning social function in the community and work level as well as the low-rated psychopathology noted at the start of study also persisted at the 3-year follow-up. The side effects were low in frequency and quality. These results show the clinical value of long-term maintenance treatment with depot neuroleptics. The results also confirm that the favourable effects of the hospital treatment demonstrated before the start of the clinical trial could be maintained. The possibilities of further improving aftercare and outpatient treatment beyond medication alone are discussed.", "contents": "Three years' maintenance neuroleptic treatment in schizophrenia--before and beyond. A group of patients with schizophrenia, initially 67 patients, was studied over a period of 3 years. After three years 36 out of 67 patients were still on the same depot neuroleptic. The main aim was to describe and compare maintenance neuroleptic therapy using two depot neuroleptics, fluphenazine decanoate and pipotiazine palmitate, given monthly. Before the outpatient care the patients had participated in the department's comprehensive hospital treatment including depot neuroleptic medication. After a 1-year clinical trial with frequent assessments of the patients, significant symptom reductions were found on all rating scales. During the last 2 years of the study only drug therapy was given. Improvement concerning social function in the community and work level as well as the low-rated psychopathology noted at the start of study also persisted at the 3-year follow-up. The side effects were low in frequency and quality. These results show the clinical value of long-term maintenance treatment with depot neuroleptics. The results also confirm that the favourable effects of the hospital treatment demonstrated before the start of the clinical trial could be maintained. The possibilities of further improving aftercare and outpatient treatment beyond medication alone are discussed."}
{"id": "PMID:24982", "title": "How schizophrenic patients change during 3 years' treatment with depot neuroleptics.", "content": "A group of patients, initially 67 individuals, with chronic schizophrenia were studied on repeated occasions during 1 year and followed up after 3 years. The patients were given depot neuroleptics, either fluphenazine decanoate or pipotiazine palmitate, at intervals of 1 month. The symptom scores from three rating scales were subjected to factor analysis. Four factors were found to explain the variance satisfactorily: one comprising psychopathological symptoms specific for schizophrenia, one relating to contact disturbances, one psychomotor activity and one representing neurotic symptoms. Analysis of these factors revealed certain differences between the treatment groups over time and demonstrated the effect of combination of psychotherapy and neuroleptic drugs in a subgroup of patients. This type of analysis of treatment results might contribute to improving our knowledge of rehabilitation of schizophrenic patients and help us to draw up giudelines for selection of suitable measures.", "contents": "How schizophrenic patients change during 3 years' treatment with depot neuroleptics. A group of patients, initially 67 individuals, with chronic schizophrenia were studied on repeated occasions during 1 year and followed up after 3 years. The patients were given depot neuroleptics, either fluphenazine decanoate or pipotiazine palmitate, at intervals of 1 month. The symptom scores from three rating scales were subjected to factor analysis. Four factors were found to explain the variance satisfactorily: one comprising psychopathological symptoms specific for schizophrenia, one relating to contact disturbances, one psychomotor activity and one representing neurotic symptoms. Analysis of these factors revealed certain differences between the treatment groups over time and demonstrated the effect of combination of psychotherapy and neuroleptic drugs in a subgroup of patients. This type of analysis of treatment results might contribute to improving our knowledge of rehabilitation of schizophrenic patients and help us to draw up giudelines for selection of suitable measures."}
{"id": "PMID:24985", "title": "Auricular tyrosine hydroxylase and dopamine-beta-hydroxylase activities and noradrenaline content in ischaemic heart disease.", "content": "Assessments were made of the tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities as well as the noradrenaline (NA) content of samples excised from right auricular tissue during cardiac surgery on a total of 55 patients with ischaemic heart disease (IHD), valvular heart disease (VHD), uncomplicated atrial septal defect (ASD) or congestive heart failure (CHF). The NA content was significantly higher in the IHD group than in the other three groups. The TH activity was highest in the IHD group although the difference was statistically significant only compared with the ASD and CHF groups. The DBH activity was also highest in the IHD group, but again the difference was statistically significant only compared with the ASD and CHF groups. In the whole material there was a significant positive correlation between the NA content and TH or DBH activity, as well as between TH and DBH activity. In the IHD group there was a significant positive correlation between heart volume and TH activity. The results suggest that at least compared with ASD and CHF, the sympathetic tone is relatively high in IHD, possibly involving an enhanced NA turnover.", "contents": "Auricular tyrosine hydroxylase and dopamine-beta-hydroxylase activities and noradrenaline content in ischaemic heart disease. Assessments were made of the tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities as well as the noradrenaline (NA) content of samples excised from right auricular tissue during cardiac surgery on a total of 55 patients with ischaemic heart disease (IHD), valvular heart disease (VHD), uncomplicated atrial septal defect (ASD) or congestive heart failure (CHF). The NA content was significantly higher in the IHD group than in the other three groups. The TH activity was highest in the IHD group although the difference was statistically significant only compared with the ASD and CHF groups. The DBH activity was also highest in the IHD group, but again the difference was statistically significant only compared with the ASD and CHF groups. In the whole material there was a significant positive correlation between the NA content and TH or DBH activity, as well as between TH and DBH activity. In the IHD group there was a significant positive correlation between heart volume and TH activity. The results suggest that at least compared with ASD and CHF, the sympathetic tone is relatively high in IHD, possibly involving an enhanced NA turnover."}
{"id": "PMID:24989", "title": "Cyclic nucleotide metabolism in solid tumor tissues.", "content": "The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells.", "contents": "Cyclic nucleotide metabolism in solid tumor tissues. The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells."}
{"id": "PMID:24994", "title": "Quantitative effects of salycylhydroxamic acid and glycerol on Trypanosoma brucei glycolysis in vitro and in vivo.", "content": "During anaerobic glycolysis in vitro in the presence of salicylhydroxamic acid, Trypanosoma brucei brucei converts glucose to equimolar amounts of glycerol and pyruvate as end products. Glycerol, whether generated endogenously and pyruvate as end products. Glycerol, whether generated endogenously or added exogenously, can inhibit anaerobic glycolysis sufficiently in vitro to result in cell death. The concomitant administration of salicylhydroxamic acid and glycerol to rats infected with T. brucei brucei results in a rapid clearance of parasitemia. Our results clearly demonstrate a new and approachable chemotherapeutic target for African trypanosomes.", "contents": "Quantitative effects of salycylhydroxamic acid and glycerol on Trypanosoma brucei glycolysis in vitro and in vivo. During anaerobic glycolysis in vitro in the presence of salicylhydroxamic acid, Trypanosoma brucei brucei converts glucose to equimolar amounts of glycerol and pyruvate as end products. Glycerol, whether generated endogenously and pyruvate as end products. Glycerol, whether generated endogenously or added exogenously, can inhibit anaerobic glycolysis sufficiently in vitro to result in cell death. The concomitant administration of salicylhydroxamic acid and glycerol to rats infected with T. brucei brucei results in a rapid clearance of parasitemia. Our results clearly demonstrate a new and approachable chemotherapeutic target for African trypanosomes."}
{"id": "PMID:24995", "title": "Effect of beta-lapachone on hydrogen peroxide production in Trypanosoma cruzi.", "content": "beta-Lapachone, an antimicrobial agent, markedly increase the generation of H2O2 in intact Trypanosoma cruzi epimastigotes (Y strain). Increase in H2O2 was determined by the horseradish peroxidase-H2O2 Compound II formation as well as by a cytochemical technique.", "contents": "Effect of beta-lapachone on hydrogen peroxide production in Trypanosoma cruzi. beta-Lapachone, an antimicrobial agent, markedly increase the generation of H2O2 in intact Trypanosoma cruzi epimastigotes (Y strain). Increase in H2O2 was determined by the horseradish peroxidase-H2O2 Compound II formation as well as by a cytochemical technique."}
{"id": "PMID:24996", "title": "[Data on the life cycle of Ribeiroia marini guadeloupensis n. ssp., a trematode sterilizing Biomphalaria glabrata in Guadeloupe].", "content": "Data on the life cycle of Ribeiroia marini guadeloupensis n.ssp., Trematode sterilizing Biomphalaria glabrata in Guadeloupe. Maintenance of the life cycle with a view to an eventual control of the populations of Molluscs. In Guadeloupe (French West Indies), the definitive hosts of Ribeiroia marini guadeloupensis n.ssp. are the two species of rats: Rattus rattus and R. norvegicus. The first intermediate host is Biomphalaria glabrata, the vector of intestinal schistosomiasis. The second intermediate host is a fish (Tilapia mossambica, Poecilia reticulata). The different stages of the life cycle are described; the transmission is studied experimentally and in natural conditions. A method for producing eggs of this Trematode in large quantities is described.", "contents": "[Data on the life cycle of Ribeiroia marini guadeloupensis n. ssp., a trematode sterilizing Biomphalaria glabrata in Guadeloupe]. Data on the life cycle of Ribeiroia marini guadeloupensis n.ssp., Trematode sterilizing Biomphalaria glabrata in Guadeloupe. Maintenance of the life cycle with a view to an eventual control of the populations of Molluscs. In Guadeloupe (French West Indies), the definitive hosts of Ribeiroia marini guadeloupensis n.ssp. are the two species of rats: Rattus rattus and R. norvegicus. The first intermediate host is Biomphalaria glabrata, the vector of intestinal schistosomiasis. The second intermediate host is a fish (Tilapia mossambica, Poecilia reticulata). The different stages of the life cycle are described; the transmission is studied experimentally and in natural conditions. A method for producing eggs of this Trematode in large quantities is described."}
{"id": "PMID:24998", "title": "Alteration of amicrofilaremia in Dipetalonema viteae infected hamsters with immunosuppressive drugs.", "content": "Dipetalonema viteae-infected hamsters with amicrofilaremic infections were subjected to immunosuppressive therapy. Methyl prednisolone acetate caused the most severe recrudescence of microfilariae while cyclophosphamide caused a low level, transient microfilaremia. Saline injected control hamsters remained amicrofilaremic. Neither drug influenced the number of adult worms recovered at necropsy in the treated hamsters compared with control hamsters.", "contents": "Alteration of amicrofilaremia in Dipetalonema viteae infected hamsters with immunosuppressive drugs. Dipetalonema viteae-infected hamsters with amicrofilaremic infections were subjected to immunosuppressive therapy. Methyl prednisolone acetate caused the most severe recrudescence of microfilariae while cyclophosphamide caused a low level, transient microfilaremia. Saline injected control hamsters remained amicrofilaremic. Neither drug influenced the number of adult worms recovered at necropsy in the treated hamsters compared with control hamsters."}
{"id": "PMID:24999", "title": "Serodiagnosis of human cysticercosis by microplate enzyme-linked immunospecific assay (ELISA).", "content": "The micro-ELISA described in this report is simple and can give objective results for the serodiagnosis of human cysticercosis. The visual assessment of results was satisfactory. The ELISA results showed a remarkably good correlation with IHA. It gave good reproudcibility. Cross-reactions were eliminated by using whole worm antigen instead of the cysticercus.", "contents": "Serodiagnosis of human cysticercosis by microplate enzyme-linked immunospecific assay (ELISA). The micro-ELISA described in this report is simple and can give objective results for the serodiagnosis of human cysticercosis. The visual assessment of results was satisfactory. The ELISA results showed a remarkably good correlation with IHA. It gave good reproudcibility. Cross-reactions were eliminated by using whole worm antigen instead of the cysticercus."}
{"id": "PMID:25000", "title": "Responses of Anopheles minimus to DDT residual spraying in a cleared forested foothill area in central Thailand.", "content": "Anopheles balabacensis balabacensis and Anopheles minimus are the main malaria vectors in Thailand. In a cleared forested foothill area in the central part of the country A. minimus was the most prevalent anopheline species found, only 6 specimens of A. b. balabacensis being collected over a 3-year period. Cattle were scarce in the area, tractors being largely used for working in the fields. This situation contributed to high man-vector contact. A minimus occurred throughout the year, with a major peak of density in the dry cool season and a smaller peak in the wet season. The contact of A. minimus with man was much higher outdoors than indoors, and studies showed the species to be an early biter, especially in the dry season, thus increasing the chance of man-vector contact. DDT spraying appeared to reduce considerably the estimated vectorial capacities, however, this effect was not maintained and malaria transmission was not interrupted. Trials with supplementary or alternative attack measures are therefore indicated in this particular ecological situation.", "contents": "Responses of Anopheles minimus to DDT residual spraying in a cleared forested foothill area in central Thailand. Anopheles balabacensis balabacensis and Anopheles minimus are the main malaria vectors in Thailand. In a cleared forested foothill area in the central part of the country A. minimus was the most prevalent anopheline species found, only 6 specimens of A. b. balabacensis being collected over a 3-year period. Cattle were scarce in the area, tractors being largely used for working in the fields. This situation contributed to high man-vector contact. A minimus occurred throughout the year, with a major peak of density in the dry cool season and a smaller peak in the wet season. The contact of A. minimus with man was much higher outdoors than indoors, and studies showed the species to be an early biter, especially in the dry season, thus increasing the chance of man-vector contact. DDT spraying appeared to reduce considerably the estimated vectorial capacities, however, this effect was not maintained and malaria transmission was not interrupted. Trials with supplementary or alternative attack measures are therefore indicated in this particular ecological situation."}
{"id": "PMID:25001", "title": "[Studies on an isolated tribe in the central highlands of Irian-Jaya (Indonesian New Guinea) within the field of tropical medicine. I. Clinical studies].", "content": "Reports on medical research examinations in the field of tropical medicine of 130 indigenous, who were examined in the central Highland of West-Irian during an interdisciplinare research project. The inhabitants of this markedly isolated area are pygmies of a strong, well proportioned build of the body and in a relative good general condition. No avitaminoses, nor symptoms of malnutrition, nor tuberculosis were discovered, in spite of an only moderate intake of albumine and carbohydrates. All examined indigenous show a distinct diastase of the musculi recti, 51.55% an enlargement of both glandulae parotes, 47% an enlargement of the lymph nodes in the differemt regions, and 11.52% an enlargement of the liver. Distinct was a violent endemy with intestinal worms and some extreme anaemia. A later publication will deal with the extensive laboratory examinations which are partly not yet completed.", "contents": "[Studies on an isolated tribe in the central highlands of Irian-Jaya (Indonesian New Guinea) within the field of tropical medicine. I. Clinical studies]. Reports on medical research examinations in the field of tropical medicine of 130 indigenous, who were examined in the central Highland of West-Irian during an interdisciplinare research project. The inhabitants of this markedly isolated area are pygmies of a strong, well proportioned build of the body and in a relative good general condition. No avitaminoses, nor symptoms of malnutrition, nor tuberculosis were discovered, in spite of an only moderate intake of albumine and carbohydrates. All examined indigenous show a distinct diastase of the musculi recti, 51.55% an enlargement of both glandulae parotes, 47% an enlargement of the lymph nodes in the differemt regions, and 11.52% an enlargement of the liver. Distinct was a violent endemy with intestinal worms and some extreme anaemia. A later publication will deal with the extensive laboratory examinations which are partly not yet completed."}
{"id": "PMID:25002", "title": "Radioimmunoassay of influenza A virus haemagglutinin. I. Preparation and properties of radioactive 125I-labelled bromelain-released haemagglutinin.", "content": "Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for eventual contamination by neuraminidase. According to specific enzymatic activities corresponding to MRC11 virus and B-HA alone respectively, B-HA contained less than 0.1% of enzymatically active neuraminidase orginally present in the virus. Gel double diffusion tests, specifities of rabbit antisera induced by B-HA, as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase has been evidently caused by antibodies to host antigenic determinaant(s) present in these sera. With respect to purity as well as radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments.", "contents": "Radioimmunoassay of influenza A virus haemagglutinin. I. Preparation and properties of radioactive 125I-labelled bromelain-released haemagglutinin. Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for eventual contamination by neuraminidase. According to specific enzymatic activities corresponding to MRC11 virus and B-HA alone respectively, B-HA contained less than 0.1% of enzymatically active neuraminidase orginally present in the virus. Gel double diffusion tests, specifities of rabbit antisera induced by B-HA, as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase has been evidently caused by antibodies to host antigenic determinaant(s) present in these sera. With respect to purity as well as radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments."}
{"id": "PMID:25003", "title": "Effect of 5-bromo-2'-deoxyuridine on the in vitro DNA synthesizing activity of polyoma virus-infected cells.", "content": "The in vitro synthesizing activity of uninfected and polyoma virus-infected mouse embryo (ME) cells was investigated by measuring the incorporation of 3H-thymidine (dTR) into acidinsoluble material in cell-free extracts. The character of the enzyme reaction was described in uninfected cells and an activating effect of 0.01 M dithiothreitol (DTT) was observed. A variation of the enzyme activity in the course of cultivation of ME cells in primary culture was demonstrated. The induction of the DNA synthesizing activity due to polyoma virus infection was markedly increased in the presence of 5-bromo-2-deoxyuridine (BUDR), what emphasizes the importance of the de novo synthesized viral and/or cellular DNA in the regulation of induction enzymes participating in DNA synthesis.", "contents": "Effect of 5-bromo-2'-deoxyuridine on the in vitro DNA synthesizing activity of polyoma virus-infected cells. The in vitro synthesizing activity of uninfected and polyoma virus-infected mouse embryo (ME) cells was investigated by measuring the incorporation of 3H-thymidine (dTR) into acidinsoluble material in cell-free extracts. The character of the enzyme reaction was described in uninfected cells and an activating effect of 0.01 M dithiothreitol (DTT) was observed. A variation of the enzyme activity in the course of cultivation of ME cells in primary culture was demonstrated. The induction of the DNA synthesizing activity due to polyoma virus infection was markedly increased in the presence of 5-bromo-2-deoxyuridine (BUDR), what emphasizes the importance of the de novo synthesized viral and/or cellular DNA in the regulation of induction enzymes participating in DNA synthesis."}
{"id": "PMID:25004", "title": "Some properties of the adenosine triphosphatase associated with herpes simplex virus and nuclear membrane of host cells.", "content": "An enzyme capable to split adenosine triphosphate (ATP) was shown to be firmly associated with mature herpes simplex virus particles purified from infected rabbit lung (ZP) cells. The enzyme localized in the viral envelope was markedly activated by bivalent cations, to the largest degree by Mg2+ at a pH optimum of 7.8--8.0. Na+ and K+ ions neither separately nor together showed any activating effect. Enzyme activity was not sensitive to the action of ouabain. No adenosine diphosphatase (ADPase) and adenosine monophosphatase (AMPase) activities were observed. ATPase activity was competitively inhibited by ADP. AMP and inorganic phosphate were without effect. The ATPase of nuclear membranes isolated from ZP cells exhibited similar properties but behaved differently to the action of sodium dithionite, dinitrophenol, oligomycin and gramicidin, as well as on heat inactivation. The origin of the virus enzyme is discussed.", "contents": "Some properties of the adenosine triphosphatase associated with herpes simplex virus and nuclear membrane of host cells. An enzyme capable to split adenosine triphosphate (ATP) was shown to be firmly associated with mature herpes simplex virus particles purified from infected rabbit lung (ZP) cells. The enzyme localized in the viral envelope was markedly activated by bivalent cations, to the largest degree by Mg2+ at a pH optimum of 7.8--8.0. Na+ and K+ ions neither separately nor together showed any activating effect. Enzyme activity was not sensitive to the action of ouabain. No adenosine diphosphatase (ADPase) and adenosine monophosphatase (AMPase) activities were observed. ATPase activity was competitively inhibited by ADP. AMP and inorganic phosphate were without effect. The ATPase of nuclear membranes isolated from ZP cells exhibited similar properties but behaved differently to the action of sodium dithionite, dinitrophenol, oligomycin and gramicidin, as well as on heat inactivation. The origin of the virus enzyme is discussed."}
{"id": "PMID:25005", "title": "Dengue viral antigens in host cell membranes.", "content": "Membranes from type 2 dengue virus (DEN-2) infected BHK cells, when used as immunogen, elicit antibodies detectable by complement fixation, hemagglutination inhibition and plaque reduction neutralization tests with suckling-mouse-brain-derived DEN-antigens. Membrane fractions from infected cells separated by sucrose density gradient centrifugation were employed as antigen in serological tests with anti-DEN-2 infected suckling mouse brain hyperimmune mouse serum and hyperimmune mouse ascitic fluid. Antigen (s) capable of fixing complement were associated with all membrane fractions, including the plasma membrane, whereas antigen capable of reacting with antihemagglutinin was largely confined to the two membrane bands consisting of (1) a mixture of rough and smooth endoplasmic reticulum (2) predominantly rough endoplasmic reticulum.", "contents": "Dengue viral antigens in host cell membranes. Membranes from type 2 dengue virus (DEN-2) infected BHK cells, when used as immunogen, elicit antibodies detectable by complement fixation, hemagglutination inhibition and plaque reduction neutralization tests with suckling-mouse-brain-derived DEN-antigens. Membrane fractions from infected cells separated by sucrose density gradient centrifugation were employed as antigen in serological tests with anti-DEN-2 infected suckling mouse brain hyperimmune mouse serum and hyperimmune mouse ascitic fluid. Antigen (s) capable of fixing complement were associated with all membrane fractions, including the plasma membrane, whereas antigen capable of reacting with antihemagglutinin was largely confined to the two membrane bands consisting of (1) a mixture of rough and smooth endoplasmic reticulum (2) predominantly rough endoplasmic reticulum."}
{"id": "PMID:25006", "title": "Studies of cell-mediated immunity to Jun\u00edn virus.", "content": "Jun\u00edn virus is uniformly lethal in newborn mice, but fails to kill adult animals. But there is direct evidence that in older mice the immunological mechanism occurs when certain conditions are fulfilled. The present results showed that in Jun\u00edn virus infection of mice, the development of the immunological mechanism occurs irrespectively of age. The induction of a regular cell-mediated immunity appears to be intimately related to multiple injections of the virus. These results were confirmed by the 51Cr release assay and by the effect of the transplanted sensitized cells. The extent of infection in the brain is another variable to be considered. Only when the virus has reached high titres and has been concentrated in the brain, the damage done by the immune attack is lethal. On the other hand the data obtained suggest that Jun\u00edn virus-sensitized spleen cells do not possess the ability to transfer significant antiviral effects to recipient preinfected newborn mice.", "contents": "Studies of cell-mediated immunity to Jun\u00edn virus. Jun\u00edn virus is uniformly lethal in newborn mice, but fails to kill adult animals. But there is direct evidence that in older mice the immunological mechanism occurs when certain conditions are fulfilled. The present results showed that in Jun\u00edn virus infection of mice, the development of the immunological mechanism occurs irrespectively of age. The induction of a regular cell-mediated immunity appears to be intimately related to multiple injections of the virus. These results were confirmed by the 51Cr release assay and by the effect of the transplanted sensitized cells. The extent of infection in the brain is another variable to be considered. Only when the virus has reached high titres and has been concentrated in the brain, the damage done by the immune attack is lethal. On the other hand the data obtained suggest that Jun\u00edn virus-sensitized spleen cells do not possess the ability to transfer significant antiviral effects to recipient preinfected newborn mice."}
{"id": "PMID:25007", "title": "Antiviral pyrimidine derivatives: binding with biopolymers and photosensitization.", "content": "Two antiviral pyrimidine derivatives, known to partially inhibit RNA dependent RNA polymerase of Mengo virus in a cell-free system, were found to bind with biopolymers. The antiviral compounds, at concentration of 100 and 50 muM and lower, showed complete inhibition of the virus-induced cytopathic effect and plaque reduction. Both compounds showed fluorescence emission with a maximum at about 500 nm under the influence of UV light of the wavelength of 366 nm. The fluorescence intensity increased upon addition of aqueous solutions of DNA, RNA and human serum albumin. This indicates that both compounds are capable of binding with nucleic acids and proteins. Based on the binding experiments alone it cannot be decided whether interference with nucleic acid template activity, enzyme function, or both are responsible for the virostatic action. Irradiation with violet light considerably enhances the virostatic activity, a fact that may be caused by photodynamic processes.", "contents": "Antiviral pyrimidine derivatives: binding with biopolymers and photosensitization. Two antiviral pyrimidine derivatives, known to partially inhibit RNA dependent RNA polymerase of Mengo virus in a cell-free system, were found to bind with biopolymers. The antiviral compounds, at concentration of 100 and 50 muM and lower, showed complete inhibition of the virus-induced cytopathic effect and plaque reduction. Both compounds showed fluorescence emission with a maximum at about 500 nm under the influence of UV light of the wavelength of 366 nm. The fluorescence intensity increased upon addition of aqueous solutions of DNA, RNA and human serum albumin. This indicates that both compounds are capable of binding with nucleic acids and proteins. Based on the binding experiments alone it cannot be decided whether interference with nucleic acid template activity, enzyme function, or both are responsible for the virostatic action. Irradiation with violet light considerably enhances the virostatic activity, a fact that may be caused by photodynamic processes."}
{"id": "PMID:25008", "title": "Effect of 3-[bis-(2-hydroxyethyl)-amino]-acetophenone-[4.5-diphenyl-oxazolyl-(2)]-hydrazone (IMET 98/69) on lethal mengo virus encephalitis.", "content": "3-[Bis-(2-hydroxyethyl)-amino]-acetophenone-[4.5-diphenyl-oxazolyl-(2)]-hydrazone (IMET 98/69) was found to afford maximum \"rates of protection\" in intraperitoneally (i.p.) or intranasally (i.n.) induced Mengo virus encephalitis in mice when administered once daily at doses of 1 mmole/kg (456.5 mg/kg) subcutaneously (s.c.) or 4 mmoles/kg (1 826 mg/kg) perorally (p.o.). Three days of treatment were sufficient if started on the day before or at the time of virus inoculation. Initiation of treatment 6 hours after inoculation was no longer effective. In a remarkable number of brains from infected and treated mice no virus was detectable, while in the remaining brains the appearance of virus was strongly delayed, and its amount significantly reduced.", "contents": "Effect of 3-[bis-(2-hydroxyethyl)-amino]-acetophenone-[4.5-diphenyl-oxazolyl-(2)]-hydrazone (IMET 98/69) on lethal mengo virus encephalitis. 3-[Bis-(2-hydroxyethyl)-amino]-acetophenone-[4.5-diphenyl-oxazolyl-(2)]-hydrazone (IMET 98/69) was found to afford maximum \"rates of protection\" in intraperitoneally (i.p.) or intranasally (i.n.) induced Mengo virus encephalitis in mice when administered once daily at doses of 1 mmole/kg (456.5 mg/kg) subcutaneously (s.c.) or 4 mmoles/kg (1 826 mg/kg) perorally (p.o.). Three days of treatment were sufficient if started on the day before or at the time of virus inoculation. Initiation of treatment 6 hours after inoculation was no longer effective. In a remarkable number of brains from infected and treated mice no virus was detectable, while in the remaining brains the appearance of virus was strongly delayed, and its amount significantly reduced."}
{"id": "PMID:25009", "title": "Reproducible plaquing system for rhinovirus serotypes in HeLa cells--agarose suspension.", "content": "HeLa cell--agarose suspension method provides an excellent plaquing system for assay of rhinovirus serotypes which ordinarily produce indistinct plaques on cell monolayers. The variable plaque size of cloned virus progeny does not involve antigenic change in phenotype as shown by plaque neutralization test. The system has proved useful for accurate and reproducible plaque assay of rhinoviruses, assay of serum neutralizing antibodies and cloning of viruses. The plaques produced are large, clear and reproducible. The factors which influence the plaquing of rhinoviruses in this system are the age of the cells, cell density and pH of the medium.", "contents": "Reproducible plaquing system for rhinovirus serotypes in HeLa cells--agarose suspension. HeLa cell--agarose suspension method provides an excellent plaquing system for assay of rhinovirus serotypes which ordinarily produce indistinct plaques on cell monolayers. The variable plaque size of cloned virus progeny does not involve antigenic change in phenotype as shown by plaque neutralization test. The system has proved useful for accurate and reproducible plaque assay of rhinoviruses, assay of serum neutralizing antibodies and cloning of viruses. The plaques produced are large, clear and reproducible. The factors which influence the plaquing of rhinoviruses in this system are the age of the cells, cell density and pH of the medium."}
{"id": "PMID:25010", "title": "Use of gel precipitin test in the diagnosis of cytomegalovirus infections.", "content": "Cytomegalovirus (CMV) antibody was detected in human sera by the gel precipitin test. The results were closely related to those obtained by complement fixation. The simplicity of the test makes it useful for the routine serological diagnosis of CMV infection.", "contents": "Use of gel precipitin test in the diagnosis of cytomegalovirus infections. Cytomegalovirus (CMV) antibody was detected in human sera by the gel precipitin test. The results were closely related to those obtained by complement fixation. The simplicity of the test makes it useful for the routine serological diagnosis of CMV infection."}
{"id": "PMID:25011", "title": "Preparation of rubella virus haemagglutinating antigen by polyethlene glycol precipitation.", "content": "Polyethylene glycol (PEG) was used for precipitation of rubella virus haemagglutinating (HA) antigen from the fluid phase of infected Vero cell cultures, maintained with or without calf serum. In both cases potent antigen preparation were obtained. When the antigen was precipitated from serum-containing medium, higher titres were obtained, provided that substrate or final product were treated with Tween 80 and ether. HA antigen obtained by PET precipitation was entirely valuable in the haemagglutination-inhibition test, as compared with antigens prepared by other methods.", "contents": "Preparation of rubella virus haemagglutinating antigen by polyethlene glycol precipitation. Polyethylene glycol (PEG) was used for precipitation of rubella virus haemagglutinating (HA) antigen from the fluid phase of infected Vero cell cultures, maintained with or without calf serum. In both cases potent antigen preparation were obtained. When the antigen was precipitated from serum-containing medium, higher titres were obtained, provided that substrate or final product were treated with Tween 80 and ether. HA antigen obtained by PET precipitation was entirely valuable in the haemagglutination-inhibition test, as compared with antigens prepared by other methods."}
{"id": "PMID:25012", "title": "Isolation of Tettnang virus from Ixodes ricinus ticks in Czechoslovakia.", "content": "Three virus strains closely related to Tettnang virus were isolated from nymphs and males of Ixodes ricinus tick in Moravia and Slovakia. The virus isolates were lethal for suckling mice on intracerebral (i.c.) inoculation but the virus titres in the brain were low. The incubation period of 5--12 days in the first mouse passage was shortened to 3 days in further passages. Infection of mice was accompanied by ultrastructural changes in the cytoplasm of neurons. Groups of spherical virus particles 75 to 80 nm in diameter occurred within simple vacuoles.", "contents": "Isolation of Tettnang virus from Ixodes ricinus ticks in Czechoslovakia. Three virus strains closely related to Tettnang virus were isolated from nymphs and males of Ixodes ricinus tick in Moravia and Slovakia. The virus isolates were lethal for suckling mice on intracerebral (i.c.) inoculation but the virus titres in the brain were low. The incubation period of 5--12 days in the first mouse passage was shortened to 3 days in further passages. Infection of mice was accompanied by ultrastructural changes in the cytoplasm of neurons. Groups of spherical virus particles 75 to 80 nm in diameter occurred within simple vacuoles."}
{"id": "PMID:25016", "title": "The nature of the renal response to chronic disorders of acid-base equilibrium.", "content": "The rate of acid excretion by the kidney appears to be determined by factors regulating the site and the rate of sodium reabsorption, rather than by a homeostatic mechanism that responds to systemic pH. This hypothesis, although unconventional, is supported by much experimental evidence, and it accounts for a wide variety of clinical and physiologic findings that heretofore have been difficult or impossible to explain.", "contents": "The nature of the renal response to chronic disorders of acid-base equilibrium. The rate of acid excretion by the kidney appears to be determined by factors regulating the site and the rate of sodium reabsorption, rather than by a homeostatic mechanism that responds to systemic pH. This hypothesis, although unconventional, is supported by much experimental evidence, and it accounts for a wide variety of clinical and physiologic findings that heretofore have been difficult or impossible to explain."}
{"id": "PMID:25017", "title": "Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension.", "content": "The relationship between sympathetic responsiveness and the blood pressure reduction induced by long-term beta-blockade was assessed in patients with essential hypertension. The increase in plasma noradrenaline concentration during physical exercise was used as an index of sympathetic responsiveness. The cardioselective beta-blocker, atenolol, was given to 16 patients with sustained benign essential hypertension for five weeks at a dose of 200 mg/day. Atenolol induced a marked decrease in blood pressure and pulse rate during recumbency, orthostasis and exercise concomitant with a marked increase in plasma noradrenaline concentration (p less than 0.0125) and a pronounced decrease in plasma renin concentration (p less than 0.01). The ratio of plasma noradrenaline during exercise to the base line concentration correlated significantly with the subsequent decrease in mean arterial blood pressure induced by beta-blockade (r = 0.840; p less than 0.001). A less significant correlation was observed between the plasma renin concentration and the subsequent decrease in mean arterial pressure (r = 0.542; p less than 0.05). The results obtained indicate that sympathetic responsiveness is an important determinant of blood pressure response to beta-blockade induced by atenolol.", "contents": "Sympathetic responsiveness and antihypertensive effect of beta-receptor blockade in essential hypertension. The relationship between sympathetic responsiveness and the blood pressure reduction induced by long-term beta-blockade was assessed in patients with essential hypertension. The increase in plasma noradrenaline concentration during physical exercise was used as an index of sympathetic responsiveness. The cardioselective beta-blocker, atenolol, was given to 16 patients with sustained benign essential hypertension for five weeks at a dose of 200 mg/day. Atenolol induced a marked decrease in blood pressure and pulse rate during recumbency, orthostasis and exercise concomitant with a marked increase in plasma noradrenaline concentration (p less than 0.0125) and a pronounced decrease in plasma renin concentration (p less than 0.01). The ratio of plasma noradrenaline during exercise to the base line concentration correlated significantly with the subsequent decrease in mean arterial blood pressure induced by beta-blockade (r = 0.840; p less than 0.001). A less significant correlation was observed between the plasma renin concentration and the subsequent decrease in mean arterial pressure (r = 0.542; p less than 0.05). The results obtained indicate that sympathetic responsiveness is an important determinant of blood pressure response to beta-blockade induced by atenolol."}
{"id": "PMID:25018", "title": "Sodium wasting, acidosis and hyperkalemia induced by methicillin interstitial nephritis. Evidence for selective distal tubular dysfunction.", "content": "A 61 year old male patient was studied who manifested dehydration, azotemia, acidosis and hyperkalemia six weeks after exposure to methicillin. Thyroid and adrenal glucocorticoid and mineralocorticoid function were normal. The dehydration was found to be caused by a profound sodium-losing nephropathy; urinary sodium ranged from 78 to 101 meq/day during a salt restricted diet. A distal renal tubular acidosis and a quantitively impaired ability to excrete potassium were also found. These defects were relatively unresponsive to mineralocorticoid or prednisone therapy. A renal biopsy specimen showed an interstitial nephritis which selectively affected distal tubules and was thought to be secondary to methicillin. The data suggest functional impairment specific for the distal tubule, but with only a modest decrease in the glomerular filtration rate.", "contents": "Sodium wasting, acidosis and hyperkalemia induced by methicillin interstitial nephritis. Evidence for selective distal tubular dysfunction. A 61 year old male patient was studied who manifested dehydration, azotemia, acidosis and hyperkalemia six weeks after exposure to methicillin. Thyroid and adrenal glucocorticoid and mineralocorticoid function were normal. The dehydration was found to be caused by a profound sodium-losing nephropathy; urinary sodium ranged from 78 to 101 meq/day during a salt restricted diet. A distal renal tubular acidosis and a quantitively impaired ability to excrete potassium were also found. These defects were relatively unresponsive to mineralocorticoid or prednisone therapy. A renal biopsy specimen showed an interstitial nephritis which selectively affected distal tubules and was thought to be secondary to methicillin. The data suggest functional impairment specific for the distal tubule, but with only a modest decrease in the glomerular filtration rate."}
{"id": "PMID:25021", "title": "New concepts in dysmenorrhea.", "content": "The etiology of primary dysmenorrhea, which is the most common gynecologic complaint and cause of lost working hours, remains obscure but merits careful scientific investigation. Recent studies suggest that increased endometrial prostaglandin production and release may be responsible for dysmenorrhea. Prostaglandins cause myometrial contractility that, if excessive, leads to uterine ischemia and pain. This hypothesis has led to clinical trials of antiprostaglandin agents such as indomethacin and fenamates, which inhibit the synthesis of prostaglandin through the prostaglandin synthetase system as well as antagonize their action at the cell receptor level. The good response of dysmenorrhea to other conventional forms of therapy such as oral contraceptives and dilatation of the cervix can be partly explained on the basis of a reduced level of prostaglandins in the menstrual fluid with such therapy. There is a definite need for further evaluation of the antiprostaglandin compounds in the treatment of dysmenorrhea so that sound formulations can be evolved for the elimination of this incapacitating disorder.", "contents": "New concepts in dysmenorrhea. The etiology of primary dysmenorrhea, which is the most common gynecologic complaint and cause of lost working hours, remains obscure but merits careful scientific investigation. Recent studies suggest that increased endometrial prostaglandin production and release may be responsible for dysmenorrhea. Prostaglandins cause myometrial contractility that, if excessive, leads to uterine ischemia and pain. This hypothesis has led to clinical trials of antiprostaglandin agents such as indomethacin and fenamates, which inhibit the synthesis of prostaglandin through the prostaglandin synthetase system as well as antagonize their action at the cell receptor level. The good response of dysmenorrhea to other conventional forms of therapy such as oral contraceptives and dilatation of the cervix can be partly explained on the basis of a reduced level of prostaglandins in the menstrual fluid with such therapy. There is a definite need for further evaluation of the antiprostaglandin compounds in the treatment of dysmenorrhea so that sound formulations can be evolved for the elimination of this incapacitating disorder."}
{"id": "PMID:25022", "title": "Subtle sequelae of brain damage. Perplexity, distractibility, and fatigue.", "content": "Subtle problems of perplexity, distractibility, and fatigue accompany all kinds of brain injury for they appear to result from disruption of accustomed neural pathways and loss or change of mental function. Emotional disturbances may mask these subtle problems, but they can also result from them. Clinical experience indicates that these problems are more apt to become stressful when the patient misinterprets or copes ineffectively with them. That these common problems of brain injured adults may be overlooked in the usual clinical examination was shown in a comparison of clinical records of 50 patients referred for neuropsychological consultation with records of 46 patient-participants in a longitudinal neuropsychological study. Significantly more reports of these problems appeared in the latter group of records. However, consultation records did reflect emotional distress. Irritability, depression, or anxiety affected all but six consultation patients and appeared with equal frequency among working patients as among those unable to work or needing full-time care. This suggests that some of their emotional distress resulted from less obvious problems than those impairing mobility, strength, or competency. Counseling can reduce the patient's vulnerability to the psychologically crippling effects of perplexity, distractibility, and fatigue. Specific recommendations for patient and family counseling are offered.", "contents": "Subtle sequelae of brain damage. Perplexity, distractibility, and fatigue. Subtle problems of perplexity, distractibility, and fatigue accompany all kinds of brain injury for they appear to result from disruption of accustomed neural pathways and loss or change of mental function. Emotional disturbances may mask these subtle problems, but they can also result from them. Clinical experience indicates that these problems are more apt to become stressful when the patient misinterprets or copes ineffectively with them. That these common problems of brain injured adults may be overlooked in the usual clinical examination was shown in a comparison of clinical records of 50 patients referred for neuropsychological consultation with records of 46 patient-participants in a longitudinal neuropsychological study. Significantly more reports of these problems appeared in the latter group of records. However, consultation records did reflect emotional distress. Irritability, depression, or anxiety affected all but six consultation patients and appeared with equal frequency among working patients as among those unable to work or needing full-time care. This suggests that some of their emotional distress resulted from less obvious problems than those impairing mobility, strength, or competency. Counseling can reduce the patient's vulnerability to the psychologically crippling effects of perplexity, distractibility, and fatigue. Specific recommendations for patient and family counseling are offered."}
{"id": "PMID:25019", "title": "The syndrome of post-splenectomy fulminant sepsis. Case report and review of the literature.", "content": "Three years after splenectomy, a middle-aged woman had two separate episodes of fulminant bacterial sepsis. She recovered each time with prompt and appropriate treatment. Her immunologic system was examined and found to be normal with respect to antibody formation against diphtheria and tetanus toxoid, granulocyte killing of staphylococci and serum opsonizing activity. Granulocytes, bursa-equivalent (B) and thymus-dependent (T) lymphocytes and serum immunoglobulins were quantitatively normal. She produced antibody against subcutaneously injected polyvalent pneumococcal vaccine. She demonstrated cutaneous anergy. The literature on this syndrome was reviewed in an attempt to ascertain why hyposplenic patients are subject of fulminant bacterial, chiefly pneumococcal, sepsis. The probably explanation is the delayed production of antibodies against the phagocytic-resistant capsule of certain bacteria which the host had not previously encountered. The incidence of this syndrome appears to be on the order of 0.5 to 1.0%/year for splenectomized older children and adults. As the syndrome is seen chiefly in splenectomized or othewise hyposplenic patients, a causal relationship seems to exist.", "contents": "The syndrome of post-splenectomy fulminant sepsis. Case report and review of the literature. Three years after splenectomy, a middle-aged woman had two separate episodes of fulminant bacterial sepsis. She recovered each time with prompt and appropriate treatment. Her immunologic system was examined and found to be normal with respect to antibody formation against diphtheria and tetanus toxoid, granulocyte killing of staphylococci and serum opsonizing activity. Granulocytes, bursa-equivalent (B) and thymus-dependent (T) lymphocytes and serum immunoglobulins were quantitatively normal. She produced antibody against subcutaneously injected polyvalent pneumococcal vaccine. She demonstrated cutaneous anergy. The literature on this syndrome was reviewed in an attempt to ascertain why hyposplenic patients are subject of fulminant bacterial, chiefly pneumococcal, sepsis. The probably explanation is the delayed production of antibodies against the phagocytic-resistant capsule of certain bacteria which the host had not previously encountered. The incidence of this syndrome appears to be on the order of 0.5 to 1.0%/year for splenectomized older children and adults. As the syndrome is seen chiefly in splenectomized or othewise hyposplenic patients, a causal relationship seems to exist."}
{"id": "PMID:25026", "title": "Smoking education programs 1960-1976.", "content": "This paper is a review of published reports, in English, of educational programs designed to change smoking behavior. Attempts to change the smoking behavior of young people have included anti-smoking campaigns, youth-to-youth programs, and a variety of message themes and teaching methods. Instruction has been presented both by teachers who were committed or persuasive and by teachers who were neutral or presented both sides of the issue. Didactic teaching, group discussion, individual study, peer instruction, and mass media have been employed. Health effects of smoking, both short- and long-term effects, have been emphasized. Most methods used with youth have shown little success. Studies of other methods have produced contradictory results. Educational programs for adults have included large scale anti-smoking campaigns, smoking cessation clinics, and a variety of more specific withdrawal methods. These methods have included individual counseling, emotional role playing, aversive conditioning, desensitization, and specific techniques to reduce the likelihood that smoking will occur in situations previously associated with smoking. Some of these techniques have produced poor results while studies of other methods have shown inconsistent results. The two methods showing the most promise are individual counseling and smoking withdrawal clinics.", "contents": "Smoking education programs 1960-1976. This paper is a review of published reports, in English, of educational programs designed to change smoking behavior. Attempts to change the smoking behavior of young people have included anti-smoking campaigns, youth-to-youth programs, and a variety of message themes and teaching methods. Instruction has been presented both by teachers who were committed or persuasive and by teachers who were neutral or presented both sides of the issue. Didactic teaching, group discussion, individual study, peer instruction, and mass media have been employed. Health effects of smoking, both short- and long-term effects, have been emphasized. Most methods used with youth have shown little success. Studies of other methods have produced contradictory results. Educational programs for adults have included large scale anti-smoking campaigns, smoking cessation clinics, and a variety of more specific withdrawal methods. These methods have included individual counseling, emotional role playing, aversive conditioning, desensitization, and specific techniques to reduce the likelihood that smoking will occur in situations previously associated with smoking. Some of these techniques have produced poor results while studies of other methods have shown inconsistent results. The two methods showing the most promise are individual counseling and smoking withdrawal clinics."}
{"id": "PMID:25027", "title": "Neuroendocrine carcinomas of the colon. Ultrastructural and biochemical evidence of their secretory function.", "content": "Four cases of malignant colonic tumors diagnosed by light microscopy as \"small cell undifferentiated carcinomas\" were shown by electron microscopy to have neurosecretory-type granules. Biochemical analysis of tumor tissue extracts disclosed the presence of considerable levels of VMA and catecholamines in all tumors; 5-HIAA was present in one tumor. Clinically, there had been no signs or symptoms attributable to those or related substances. Similar observations have been reported in a variety of neuroendocrine neoplasms; for example, the demonstration of neurosecretory-type granules and determination of amine or peptide materials in tumor tissue or body fluids may not be necessarily reflected in clinical hormonal syndromes or obvious metabolic abnormalities. Our structural and biochemical observations indicate that, regardless of clinically evident hormonal activity or lack thereof, some small cell \"undifferentiated\" colonic cancers derive from APUD elements, and therefore they should be classified within the group of neuroendocrine carcinomas. The evident secretory capabilities of these carcinomas suggest obvious diagnostic possibilities and could conceivably lead to a reappraisal of current therapy.", "contents": "Neuroendocrine carcinomas of the colon. Ultrastructural and biochemical evidence of their secretory function. Four cases of malignant colonic tumors diagnosed by light microscopy as \"small cell undifferentiated carcinomas\" were shown by electron microscopy to have neurosecretory-type granules. Biochemical analysis of tumor tissue extracts disclosed the presence of considerable levels of VMA and catecholamines in all tumors; 5-HIAA was present in one tumor. Clinically, there had been no signs or symptoms attributable to those or related substances. Similar observations have been reported in a variety of neuroendocrine neoplasms; for example, the demonstration of neurosecretory-type granules and determination of amine or peptide materials in tumor tissue or body fluids may not be necessarily reflected in clinical hormonal syndromes or obvious metabolic abnormalities. Our structural and biochemical observations indicate that, regardless of clinically evident hormonal activity or lack thereof, some small cell \"undifferentiated\" colonic cancers derive from APUD elements, and therefore they should be classified within the group of neuroendocrine carcinomas. The evident secretory capabilities of these carcinomas suggest obvious diagnostic possibilities and could conceivably lead to a reappraisal of current therapy."}
{"id": "PMID:25029", "title": "Biochemical tests for the detection of alcoholism: comparison of plasma alpha-amino-n-butyric acid with other available tests.", "content": "The measurement of AANB relative to leucine was found to be a useful biochemical test for the detection of chronic alcohol consumption. This test, in combination with GGTP determinations, provided a sensitive means of detection (81% positive) for chronic alcohol consumption with a minimum of false positive determinations (2%).", "contents": "Biochemical tests for the detection of alcoholism: comparison of plasma alpha-amino-n-butyric acid with other available tests. The measurement of AANB relative to leucine was found to be a useful biochemical test for the detection of chronic alcohol consumption. This test, in combination with GGTP determinations, provided a sensitive means of detection (81% positive) for chronic alcohol consumption with a minimum of false positive determinations (2%)."}
{"id": "PMID:25030", "title": "Pain and clinical thrombophlebitis following intravenous diazepam and lorazepam.", "content": "Eighty-seven per cent of surgical patients receiving undiluted diazepam experienced pain on injection while 6-16%, depending on the dose, manifested evidence of clinical thrombophlebitis. This was improved when diazepam, 10 mg, was diluted to 20-40 ml with intravenous solution. In contrast, lorazepam appeared to have minimal irritative or injurious effects on veins whether undiluted or diluted. In view of these results and clinical studies reporting a higher patient acceptance of lorazepam than diazepam, lorazepam may be a superior drug for use in anaesthesia.", "contents": "Pain and clinical thrombophlebitis following intravenous diazepam and lorazepam. Eighty-seven per cent of surgical patients receiving undiluted diazepam experienced pain on injection while 6-16%, depending on the dose, manifested evidence of clinical thrombophlebitis. This was improved when diazepam, 10 mg, was diluted to 20-40 ml with intravenous solution. In contrast, lorazepam appeared to have minimal irritative or injurious effects on veins whether undiluted or diluted. In view of these results and clinical studies reporting a higher patient acceptance of lorazepam than diazepam, lorazepam may be a superior drug for use in anaesthesia."}
{"id": "PMID:25031", "title": "Arterialized capillary blood used to determine the acid-base and blood gas status of dogs.", "content": "Blood samples were collected by microhematocrit tube from posterior medial margin of the shaved, but otherwise untreated, canine ear. Acid-base and blood gas values of these samples were compared with the values of samples obtained simultaneously from the carotid artery. The arterialized nature of capillary blood from the canine ear was demonstrated under various degrees of chemical restraint and during conditions of extreme hypoxic acidosis to hyperventilatory alkalosis. Once a week determinations of acid-base and blood gas status with such arterialized capillary blood from a group of awake dogs showed within-subject variance to be significantly less (P less than 0.05) than between-subject variance; thus, uniqueness of individual dogs was reliably revealed. This technique also was used to demonstrated breed differences for acid-base and blood gas characteristics.", "contents": "Arterialized capillary blood used to determine the acid-base and blood gas status of dogs. Blood samples were collected by microhematocrit tube from posterior medial margin of the shaved, but otherwise untreated, canine ear. Acid-base and blood gas values of these samples were compared with the values of samples obtained simultaneously from the carotid artery. The arterialized nature of capillary blood from the canine ear was demonstrated under various degrees of chemical restraint and during conditions of extreme hypoxic acidosis to hyperventilatory alkalosis. Once a week determinations of acid-base and blood gas status with such arterialized capillary blood from a group of awake dogs showed within-subject variance to be significantly less (P less than 0.05) than between-subject variance; thus, uniqueness of individual dogs was reliably revealed. This technique also was used to demonstrated breed differences for acid-base and blood gas characteristics."}
{"id": "PMID:25032", "title": "Type-specific pneumococcal respiratory disease in the elderly and chronically III.", "content": "Type-specific pneumococcal respiratory disease was studied in a chronic-disease hospital during a 27-month period. Isolates from 50 patients with pneumonia and from 24 patients with chronic bronchitis were available for typing. Vaccine types were isolated from 74 per cent of patients with pneumonia and from 42 per cent of patients with chronic bronchitis. Pneumococcal types isolated from 5 of 8 patients with bacteremia and from 6 of 9 patients who died were also included in the vaccine. The data suggest that, theoretically, closed populations of elderly and chronically ill patients would benefit from vaccination in an attempt to control pneumococcal pneumonia. Less clear is the potential role vaccination in patients with chronic bronchitis.", "contents": "Type-specific pneumococcal respiratory disease in the elderly and chronically III. Type-specific pneumococcal respiratory disease was studied in a chronic-disease hospital during a 27-month period. Isolates from 50 patients with pneumonia and from 24 patients with chronic bronchitis were available for typing. Vaccine types were isolated from 74 per cent of patients with pneumonia and from 42 per cent of patients with chronic bronchitis. Pneumococcal types isolated from 5 of 8 patients with bacteremia and from 6 of 9 patients who died were also included in the vaccine. The data suggest that, theoretically, closed populations of elderly and chronically ill patients would benefit from vaccination in an attempt to control pneumococcal pneumonia. Less clear is the potential role vaccination in patients with chronic bronchitis."}
{"id": "PMID:25034", "title": "Subacute thyroiditis with increased serum alkaline phosphatase.", "content": "Three patients had subacute thyroiditis and elevated serum alkaline phosphatase, presumably related to the thyroiditis. Concomitant elevation of the serum gamma-glutamyl transferase suggested that the alkaline phosphatase was of hepatic origin. The elevation of the serum alkaline phosphatase could not be definitely related to the degree or duration of elevation of the serum thyroxine. The combination of elevated serum alkaline phosphatase with the systemic symptoms of subacute thyroiditis may obscure the diagnosis, especially if patients have little or no neck pain.", "contents": "Subacute thyroiditis with increased serum alkaline phosphatase. Three patients had subacute thyroiditis and elevated serum alkaline phosphatase, presumably related to the thyroiditis. Concomitant elevation of the serum gamma-glutamyl transferase suggested that the alkaline phosphatase was of hepatic origin. The elevation of the serum alkaline phosphatase could not be definitely related to the degree or duration of elevation of the serum thyroxine. The combination of elevated serum alkaline phosphatase with the systemic symptoms of subacute thyroiditis may obscure the diagnosis, especially if patients have little or no neck pain."}
{"id": "PMID:25035", "title": "Clinical and biochemical heterogeneity of depressive disorders.", "content": "Indirect evidence, mostly pharmacologic, has suggested a role for brain neurotransmitter amines such as norepinephrine in the production of depression or mania. Clinical investigations have supported this concept but also indicate that depression is probably a biochemically heterogeneous group of illnesses. There may be a clinically, biochemically, and pharmacologically definable subtype of depression in which there is a disorder of norepinephrine metabolism or disposition in brain. I review here the experimental data from which this hypothesis is derived.", "contents": "Clinical and biochemical heterogeneity of depressive disorders. Indirect evidence, mostly pharmacologic, has suggested a role for brain neurotransmitter amines such as norepinephrine in the production of depression or mania. Clinical investigations have supported this concept but also indicate that depression is probably a biochemically heterogeneous group of illnesses. There may be a clinically, biochemically, and pharmacologically definable subtype of depression in which there is a disorder of norepinephrine metabolism or disposition in brain. I review here the experimental data from which this hypothesis is derived."}
{"id": "PMID:25037", "title": "Relationship of pH of blood and aqueous with vitamin C.", "content": "Blood pH, aqueous pH, and intraocular tension were noted in 20 albino rabbits before and after administration of vitamin C in oral dosage of 7.5 gm/kg/day (in 4 equal divided doses for one week). A significant difference was noted in changes of blood pH and fall in intraocular tension but aqueous pH did not show any change. In 20 glaucoma patients there was no significant change in pH of blood of glaucoma after administration of vitamin C in 3.5 gm/kg body weight per day by oral route for one week (in 4 equal divided doses).", "contents": "Relationship of pH of blood and aqueous with vitamin C. Blood pH, aqueous pH, and intraocular tension were noted in 20 albino rabbits before and after administration of vitamin C in oral dosage of 7.5 gm/kg/day (in 4 equal divided doses for one week). A significant difference was noted in changes of blood pH and fall in intraocular tension but aqueous pH did not show any change. In 20 glaucoma patients there was no significant change in pH of blood of glaucoma after administration of vitamin C in 3.5 gm/kg body weight per day by oral route for one week (in 4 equal divided doses)."}
{"id": "PMID:25039", "title": "Origin of an elevated plasma alkaline phosphatase activity in non-jaundiced patients.", "content": "Samples from 260 non-jaundiced patients with elevated plasma alkaline phosphatase activities were analysed for gamma-glutamyltransferase and 5'-nucleotidase activity, and for alkaline phosphatase isoenzyme pattern. The plasma gamma-glutamyltransferase activity was found to be a more sensitive index than that of plasma 5'-nucleotidase in confirming the presence of a liver component of the elevated plasma alkaline phosphatase. If the gamma-glutamyltransferase level is normal it is probable that the increase in plasma alkaline phosphatase activity is of bone origin. However, and elevated gamma-glutamyltransferase result does not exclude a bone component; in this situation plasma alkaline phosphatase isoenzymes should be estimated. The causes of elevated activities of plasma alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase, found in this investigation were generally the same as those found by other worker. The effect of treatment by drugs on gamma-glutamyltransferase, an inducible enzyme, needs more investigation.", "contents": "Origin of an elevated plasma alkaline phosphatase activity in non-jaundiced patients. Samples from 260 non-jaundiced patients with elevated plasma alkaline phosphatase activities were analysed for gamma-glutamyltransferase and 5'-nucleotidase activity, and for alkaline phosphatase isoenzyme pattern. The plasma gamma-glutamyltransferase activity was found to be a more sensitive index than that of plasma 5'-nucleotidase in confirming the presence of a liver component of the elevated plasma alkaline phosphatase. If the gamma-glutamyltransferase level is normal it is probable that the increase in plasma alkaline phosphatase activity is of bone origin. However, and elevated gamma-glutamyltransferase result does not exclude a bone component; in this situation plasma alkaline phosphatase isoenzymes should be estimated. The causes of elevated activities of plasma alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase, found in this investigation were generally the same as those found by other worker. The effect of treatment by drugs on gamma-glutamyltransferase, an inducible enzyme, needs more investigation."}
{"id": "PMID:25043", "title": "Purification and some properties of riboflavin synthetase from Bacillus stearothermophilus ATCC 8005.", "content": "A riboflavin synthetase was purified 51-fold from a thermophilic organism, Bacillus stearothermophilus ATCC 8005, that grew at 40 to 72 degrees C. Some of the properties of the enzyme are: (i) its temperature optimum was 95 degrees C, and the activity was negligible below 40 degrees C; (ii) the Arrhenius plot of the initial reaction rates was concave upward, with a break at 65 degrees C, and the apparent activation energies below and above 65 degrees C were 4.2 X 10(4) and 6.7 X 10(4) J/mol, respectively; (iii) the enzyme was fairly stable up to 60 degrees C without 6,7-dimethyl-8-ribityllumazine; this substance protected the enzyme from inactivation above 60 to 97 degrees C; (iv) the pH range for stability was 6.0 to 10.0 at 26 degrees C and 6.3 to 7.6 at 55 degrees C; (v) the enzyme was highly resistant at 26 degrees C to denaturation in 8 M urea, but the tolerance was extremely low at 55 degrees C; (vi) its molecular weight was estimated at 45,000; (vii) the Km for 6,7-dimethyl-8-ribityllumazine was 23 micrometer at 55 degrees C and 29 micrometer at 75 degrees C; (viii) its pH optimum was 6.7 to 7.2; (ix) 6-methyl-7-hydroxy-8-ribityllumazine was a competitive inhibitor (Ki = 0.18 micrometer); (x) the activity was sensitive to heavy-metal ions and thiol reagents; (xi) the enzyme did not require cofactor or a carbon donor; and (xii) the molar ratio of 6,7-dimethyl-8-ribityllumazine consumption to riboflavin formation was 2 throughout the entire reaction. Properties i through vi distinguish this enzyme from riboflavin synthetases purified by other investigators from mesophilic organisms, Ashbya gossypii, Eremothecium ashbyii, Escherichia coli, yeast, and spinach.", "contents": "Purification and some properties of riboflavin synthetase from Bacillus stearothermophilus ATCC 8005. A riboflavin synthetase was purified 51-fold from a thermophilic organism, Bacillus stearothermophilus ATCC 8005, that grew at 40 to 72 degrees C. Some of the properties of the enzyme are: (i) its temperature optimum was 95 degrees C, and the activity was negligible below 40 degrees C; (ii) the Arrhenius plot of the initial reaction rates was concave upward, with a break at 65 degrees C, and the apparent activation energies below and above 65 degrees C were 4.2 X 10(4) and 6.7 X 10(4) J/mol, respectively; (iii) the enzyme was fairly stable up to 60 degrees C without 6,7-dimethyl-8-ribityllumazine; this substance protected the enzyme from inactivation above 60 to 97 degrees C; (iv) the pH range for stability was 6.0 to 10.0 at 26 degrees C and 6.3 to 7.6 at 55 degrees C; (v) the enzyme was highly resistant at 26 degrees C to denaturation in 8 M urea, but the tolerance was extremely low at 55 degrees C; (vi) its molecular weight was estimated at 45,000; (vii) the Km for 6,7-dimethyl-8-ribityllumazine was 23 micrometer at 55 degrees C and 29 micrometer at 75 degrees C; (viii) its pH optimum was 6.7 to 7.2; (ix) 6-methyl-7-hydroxy-8-ribityllumazine was a competitive inhibitor (Ki = 0.18 micrometer); (x) the activity was sensitive to heavy-metal ions and thiol reagents; (xi) the enzyme did not require cofactor or a carbon donor; and (xii) the molar ratio of 6,7-dimethyl-8-ribityllumazine consumption to riboflavin formation was 2 throughout the entire reaction. Properties i through vi distinguish this enzyme from riboflavin synthetases purified by other investigators from mesophilic organisms, Ashbya gossypii, Eremothecium ashbyii, Escherichia coli, yeast, and spinach."}
{"id": "PMID:25040", "title": "A supplement to alkaline phosphatase fractionations: utilization of gamma-glutamyl transpeptidase and hydroxyproline assays.", "content": "Fractionation of serum alkaline phosphatase by either biochemical or electrophoretic techniques is often insufficient to determine the source of the elevated serum enzyme. In 31 unselected patients with high serum alkaline phosphatase a simultaneous determination of serum gamma glutamyl transpeptidase and urinary hydroxyproline excretion rates was performed, in addition to urea denaturation and L-phenylalanine inhibition tests. Of 25 patients with definite diagnosis, the urea denaturation test correctly identified the source of the elevated serum alkaline phosphatase (ALP) in 16 (64 percent). The serum gamma-glutamyl transpeptidase (GGTP) alone predicted the correct diagnosis in 64 percent of the cases and the urinary hydroxyproline (HOP) alone in 69 percent. When all three tests were performed simultaneously, the combination of results identified the source of the ALP in 88 percent of the cases. It is believed that this combination offers better sensitivity and specificity than any of the three tests used individually.", "contents": "A supplement to alkaline phosphatase fractionations: utilization of gamma-glutamyl transpeptidase and hydroxyproline assays. Fractionation of serum alkaline phosphatase by either biochemical or electrophoretic techniques is often insufficient to determine the source of the elevated serum enzyme. In 31 unselected patients with high serum alkaline phosphatase a simultaneous determination of serum gamma glutamyl transpeptidase and urinary hydroxyproline excretion rates was performed, in addition to urea denaturation and L-phenylalanine inhibition tests. Of 25 patients with definite diagnosis, the urea denaturation test correctly identified the source of the elevated serum alkaline phosphatase (ALP) in 16 (64 percent). The serum gamma-glutamyl transpeptidase (GGTP) alone predicted the correct diagnosis in 64 percent of the cases and the urinary hydroxyproline (HOP) alone in 69 percent. When all three tests were performed simultaneously, the combination of results identified the source of the ALP in 88 percent of the cases. It is believed that this combination offers better sensitivity and specificity than any of the three tests used individually."}
{"id": "PMID:25044", "title": "Formation of glycosidases in batch and continuous culture of Bacteroides fragilis.", "content": "Nine strains of bacteroides fragilis were cultivated in stirred fermentors and tested for their ability to produce glycosidases. B. fragilis subsp. vulgatus B70 was used for optimizing the production of glycosidases. The highest bacterial yield was obtained in proteose peptone-yeast extract medium. The optimum pH for maximal bacterial yield was 7.0, and the optimum temperature for growth was 37 degrees C. The formation of glycosidases was optimal between pH 6.5 and 7.5, and the optimum temperature for synthesis of glycosidases was between 33 and 37 degrees C. Culture under controlled conditions in fermentors gave more reproducible production of glycosidases than static cultures in bottles. The strain was also grown in continuous culture at a dilution rate of 0.1 liter/h at pH 7.0 and 37 degrees C with a yield of 2.0 mg of dry weight per ml in the complex medium. The formation of glycosidases remained constant during the entire continuous process.", "contents": "Formation of glycosidases in batch and continuous culture of Bacteroides fragilis. Nine strains of bacteroides fragilis were cultivated in stirred fermentors and tested for their ability to produce glycosidases. B. fragilis subsp. vulgatus B70 was used for optimizing the production of glycosidases. The highest bacterial yield was obtained in proteose peptone-yeast extract medium. The optimum pH for maximal bacterial yield was 7.0, and the optimum temperature for growth was 37 degrees C. The formation of glycosidases was optimal between pH 6.5 and 7.5, and the optimum temperature for synthesis of glycosidases was between 33 and 37 degrees C. Culture under controlled conditions in fermentors gave more reproducible production of glycosidases than static cultures in bottles. The strain was also grown in continuous culture at a dilution rate of 0.1 liter/h at pH 7.0 and 37 degrees C with a yield of 2.0 mg of dry weight per ml in the complex medium. The formation of glycosidases remained constant during the entire continuous process."}
{"id": "PMID:25045", "title": "Clear, defined medium for the sporulation of Clostridium perfringens.", "content": "A new, defined medium for the sporulation of Clostridium perfringens is presented. Sporulation levels exceeding 10(6) to 10(7) heat-resistant spores per ml were obtained for seven strains: PS49, PS52, FD-1, T-65, NCTC strains 8798, 8238, and 10240. In the presence of theophylline, a methylxanthine, higher levels of heat-resistant spores were attained for strains PS49, PS52, FD-1, ant T-65; photomicrographs demonstrated a higher fraction of sporulating cells when these strains were grown in the presence of methylxanthines. Use of washed, highly diluted (less than 100 cells) inocula resulted in no reduction in spore yield. Strain KA3 grew well but sporulated poorly on this medium. The medium was clear and free of precipitate when small amounts (100 microgram/ml) of methylxanthine were incorporated.", "contents": "Clear, defined medium for the sporulation of Clostridium perfringens. A new, defined medium for the sporulation of Clostridium perfringens is presented. Sporulation levels exceeding 10(6) to 10(7) heat-resistant spores per ml were obtained for seven strains: PS49, PS52, FD-1, T-65, NCTC strains 8798, 8238, and 10240. In the presence of theophylline, a methylxanthine, higher levels of heat-resistant spores were attained for strains PS49, PS52, FD-1, ant T-65; photomicrographs demonstrated a higher fraction of sporulating cells when these strains were grown in the presence of methylxanthines. Use of washed, highly diluted (less than 100 cells) inocula resulted in no reduction in spore yield. Strain KA3 grew well but sporulated poorly on this medium. The medium was clear and free of precipitate when small amounts (100 microgram/ml) of methylxanthine were incorporated."}
{"id": "PMID:25046", "title": "Simple bacterial preservation medium and its application to proficiency testing in water bacteriology.", "content": "A medium composed of nutrient broth, 1.8% boric acid, and 1% sodium chloride at pH 7.0 was shown to maintain the stability of Escherichia coli cultures for up to 10 days at room temperature. By using this preservation medium for preparing a simulated sample a successful proficiency test survey in water bacteriology was conducted.", "contents": "Simple bacterial preservation medium and its application to proficiency testing in water bacteriology. A medium composed of nutrient broth, 1.8% boric acid, and 1% sodium chloride at pH 7.0 was shown to maintain the stability of Escherichia coli cultures for up to 10 days at room temperature. By using this preservation medium for preparing a simulated sample a successful proficiency test survey in water bacteriology was conducted."}
{"id": "PMID:25047", "title": "Reduction of azo dyes by intestinal anaerobes.", "content": "Reduction of seven azo dyes (amaranth, Ponceau SX, Allura Red, Sunset Yellow, tartrazine, Orange II, and methyl orange) was carried out by cell suspensions of predominant intestinal anaerobes. It was optimal at pH 7.4 in 0.4 M phosphate buffer and inhibited by glucose. Flavin mononucleotide caused a marked enhancement of azo reduction by Bacteroides thetaiotaomicron. Other electron carriers, e.g., methyl viologen, benzyl viologen, phenosafranin, neutral red, crystal violet, flavin adenine dinucleotide, menadione, and Janus Green B can replace flavin mononucleotide. These data suggest that an extracellular shuttle is required for azo reduction.", "contents": "Reduction of azo dyes by intestinal anaerobes. Reduction of seven azo dyes (amaranth, Ponceau SX, Allura Red, Sunset Yellow, tartrazine, Orange II, and methyl orange) was carried out by cell suspensions of predominant intestinal anaerobes. It was optimal at pH 7.4 in 0.4 M phosphate buffer and inhibited by glucose. Flavin mononucleotide caused a marked enhancement of azo reduction by Bacteroides thetaiotaomicron. Other electron carriers, e.g., methyl viologen, benzyl viologen, phenosafranin, neutral red, crystal violet, flavin adenine dinucleotide, menadione, and Janus Green B can replace flavin mononucleotide. These data suggest that an extracellular shuttle is required for azo reduction."}
{"id": "PMID:25048", "title": "Concentration of poliovirus from tap water onto membrane filters with aluminum chloride at ambient pH levels.", "content": "A method is described for the concentration of an enterovirus from large volumes of tap water by addition of small amounts of aluminum chloride to enhance virus removal by membrane filters. Tap water treated with 2 X 10(-5) M aluminum chloride showed a slight decrease in pH (less than 0.5), a slight increase in turbidity, and enhanced removal of poliovirus by membrane filters. Virus was quantitatively recovered by treating the filters with a basic buffer, and this eluate was reconcentrated to a small volume by adsorption to aluminum hydroxide flocs. Using these procedures, virus from 1,000 liters of water was reduced to a final eluate of 20 to 80 ml with a mean recovery of 70%.", "contents": "Concentration of poliovirus from tap water onto membrane filters with aluminum chloride at ambient pH levels. A method is described for the concentration of an enterovirus from large volumes of tap water by addition of small amounts of aluminum chloride to enhance virus removal by membrane filters. Tap water treated with 2 X 10(-5) M aluminum chloride showed a slight decrease in pH (less than 0.5), a slight increase in turbidity, and enhanced removal of poliovirus by membrane filters. Virus was quantitatively recovered by treating the filters with a basic buffer, and this eluate was reconcentrated to a small volume by adsorption to aluminum hydroxide flocs. Using these procedures, virus from 1,000 liters of water was reduced to a final eluate of 20 to 80 ml with a mean recovery of 70%."}
{"id": "PMID:25053", "title": "Hypotensive and bradycardic effects of classical alpha-sympathomimetic drugs upon intravenous administration to pentobarbitone-anaesthetized rats.", "content": "The effects of the classical alpha-sympathomimetic drugs naphazoline, tramazoline, xylometazoline, tetryzoline and oxymetazoline on blood pressure and heart rate of pentobarbitone-anaesthetized (75 mg/kg; i.p.) normotensive rats were studied following intravenous injections. With the aid of this experimental animal model a dose dependent decrease in mean arterial pressure and heart rate could be established for these agents, oxymetazoline excepted, for which only the bradycardia could be quantified. It is suggested that central alpha-adrenoceptors are involved in the mechanism of this cardiovascular inhibition in view of the most specific alpha-adrenoceptor-stimulating properties of these ddrugs. Additionally, the results indicate that the use of pentobarbitone as the anaesthetic enhances the hypotensive action of these agents, so that their pronounced peripheral vasopressive response can be overcome.", "contents": "Hypotensive and bradycardic effects of classical alpha-sympathomimetic drugs upon intravenous administration to pentobarbitone-anaesthetized rats. The effects of the classical alpha-sympathomimetic drugs naphazoline, tramazoline, xylometazoline, tetryzoline and oxymetazoline on blood pressure and heart rate of pentobarbitone-anaesthetized (75 mg/kg; i.p.) normotensive rats were studied following intravenous injections. With the aid of this experimental animal model a dose dependent decrease in mean arterial pressure and heart rate could be established for these agents, oxymetazoline excepted, for which only the bradycardia could be quantified. It is suggested that central alpha-adrenoceptors are involved in the mechanism of this cardiovascular inhibition in view of the most specific alpha-adrenoceptor-stimulating properties of these ddrugs. Additionally, the results indicate that the use of pentobarbitone as the anaesthetic enhances the hypotensive action of these agents, so that their pronounced peripheral vasopressive response can be overcome."}
{"id": "PMID:25054", "title": "[Arterial malformations and Takayashu disease].", "content": "The authors report a recent series of 5 cases with Takayashu's disease and discuss the common pathological presentation of malformations of the arterial trunk, caused by disorderd development of the arterial system or by later segmental arrested development of the large trunks. The disease, which presents in the young adult as a diffuse inflammatory process, is probably auto-immune, but has its foundations in embryonic and foetal development.", "contents": "[Arterial malformations and Takayashu disease]. The authors report a recent series of 5 cases with Takayashu's disease and discuss the common pathological presentation of malformations of the arterial trunk, caused by disorderd development of the arterial system or by later segmental arrested development of the large trunks. The disease, which presents in the young adult as a diffuse inflammatory process, is probably auto-immune, but has its foundations in embryonic and foetal development."}
{"id": "PMID:25055", "title": "[Action of a sodium lactate perfusion on the hemodynamic effects of beta-blockaders].", "content": "In 15 dogs who had been given propranolol and 5 humans who had been given Pindolol, an infusion of sodium lactate produced: 1) an increased in blood lactate levels and pH; 2) an increase in the cardiac index; 3) a state in which an infusion of isoproterenol (inactive on its own) could act as it would have done had the betaadrenergic receptors not been blocked. A perfusion of lactic acid which was sufficient to cause the variations in pH and blood lactate levels that are seen with exercise had no action on the heart rate nor on the cardiac index of 10 dogs treated with propranolol and could not re-establish the betastimulating properties of isoproterenol. Finally, alkalosis produced by an infusion of THAM in 13 dogs or sodium bicarbonate in 2 humans, changed neither the cardiac index nor the heart rate, nor the response to isoproterenol after a betaadrenergic blockade. Infusion of sodium lactate associated with isoproterenol could be used to combat the depressent effects of betablockers in patients with cardiac disorders.", "contents": "[Action of a sodium lactate perfusion on the hemodynamic effects of beta-blockaders]. In 15 dogs who had been given propranolol and 5 humans who had been given Pindolol, an infusion of sodium lactate produced: 1) an increased in blood lactate levels and pH; 2) an increase in the cardiac index; 3) a state in which an infusion of isoproterenol (inactive on its own) could act as it would have done had the betaadrenergic receptors not been blocked. A perfusion of lactic acid which was sufficient to cause the variations in pH and blood lactate levels that are seen with exercise had no action on the heart rate nor on the cardiac index of 10 dogs treated with propranolol and could not re-establish the betastimulating properties of isoproterenol. Finally, alkalosis produced by an infusion of THAM in 13 dogs or sodium bicarbonate in 2 humans, changed neither the cardiac index nor the heart rate, nor the response to isoproterenol after a betaadrenergic blockade. Infusion of sodium lactate associated with isoproterenol could be used to combat the depressent effects of betablockers in patients with cardiac disorders."}
{"id": "PMID:25056", "title": "Bacterial 2,3-butanediol dehydrogenases.", "content": "Enterobacter aerogenes, Aeromonas hydrophila, Serratia marcescens and Staphylococcus aureus possessing L(+)-butanediol dehydrogenase produced mainly meso-butanediol and small amounts of optically active butanediol; Acetobacter suboxydans, Bacillus polymyxa and Erwinia carotovora containing D(-)-butanediol dehydrogenase produced more optically active butanediol than meso-butanediol. Resting and growing cells of these organisms oxidezed only one enantiomer of racemic butanediol. The D(-)-butanediol dehydrogenase from Bacillus polymyxa was partially purified (30-fold) with a specific activity of 24.5. Except NAD and NADH no other cofactors were required. Optimum pH-values for oxidation and reduction were pH 9 and pH 7, respectively. The optimum temperature was about 60 degrees C. The molecular weight was 100000 to 107000. The Km-values were 3.3 mM for D(-)butanediol, 6.25 mM for meso-butanediol, 0.53 mM for acetoin, 0.2 mM for NAD, 0.1 mM for NADH, 87 mM for diacetyl, 38 mM for 1,2-propanediol; 2,3-pentanedion was not a substrate for this enzyme. The L(+)butanediol dehydrogenase from Serratia marcescens was purified 57-fold (specific activity 22.3). Besides NAD or NADH no cofactors were required. The optimum value for oxidation was about pH9 and for reduction pH 4.5. The optimum temperature was 32-36 degrees C. The molecular weight was 100000 to 107000. The Km-values were 5 mM for meso-butanediol, 10 mM for racemic butanediol, 6.45 for acetoin, 1 mM for NAD, 0.25 mM for NADH, 2.08 mM for diacetyl, 16.7 mM for 2,3-pentanedion and 11.8 mM for 1,2-propanediol.", "contents": "Bacterial 2,3-butanediol dehydrogenases. Enterobacter aerogenes, Aeromonas hydrophila, Serratia marcescens and Staphylococcus aureus possessing L(+)-butanediol dehydrogenase produced mainly meso-butanediol and small amounts of optically active butanediol; Acetobacter suboxydans, Bacillus polymyxa and Erwinia carotovora containing D(-)-butanediol dehydrogenase produced more optically active butanediol than meso-butanediol. Resting and growing cells of these organisms oxidezed only one enantiomer of racemic butanediol. The D(-)-butanediol dehydrogenase from Bacillus polymyxa was partially purified (30-fold) with a specific activity of 24.5. Except NAD and NADH no other cofactors were required. Optimum pH-values for oxidation and reduction were pH 9 and pH 7, respectively. The optimum temperature was about 60 degrees C. The molecular weight was 100000 to 107000. The Km-values were 3.3 mM for D(-)butanediol, 6.25 mM for meso-butanediol, 0.53 mM for acetoin, 0.2 mM for NAD, 0.1 mM for NADH, 87 mM for diacetyl, 38 mM for 1,2-propanediol; 2,3-pentanedion was not a substrate for this enzyme. The L(+)butanediol dehydrogenase from Serratia marcescens was purified 57-fold (specific activity 22.3). Besides NAD or NADH no cofactors were required. The optimum value for oxidation was about pH9 and for reduction pH 4.5. The optimum temperature was 32-36 degrees C. The molecular weight was 100000 to 107000. The Km-values were 5 mM for meso-butanediol, 10 mM for racemic butanediol, 6.45 for acetoin, 1 mM for NAD, 0.25 mM for NADH, 2.08 mM for diacetyl, 16.7 mM for 2,3-pentanedion and 11.8 mM for 1,2-propanediol."}
{"id": "PMID:25059", "title": "Significance of microbial contamination of stored cadaver kidneys.", "content": "The importance of microbial contamination of cadaver kidneys was assessed in 83 consecutively stored and transplanted kidneys. Fourteen kidneys had a single positive culture during storage and five had multiple positive cultures. Only one postoperative infection could be traced to kidney contamination during storage (Candida wound infection). In three of 64 patients who received noncontaminated kidneys, posttransplant wound infections developed. No wound infections occurred in 35 patients who received prophylactic antibiotics, whereas four wound infections occurred in 48 patients without antibiotic coverage. It is concluded that, although microbial contamination of stored cadaver kidneys occurs commonly, it is not an important source of infection in renal transplant recipients.", "contents": "Significance of microbial contamination of stored cadaver kidneys. The importance of microbial contamination of cadaver kidneys was assessed in 83 consecutively stored and transplanted kidneys. Fourteen kidneys had a single positive culture during storage and five had multiple positive cultures. Only one postoperative infection could be traced to kidney contamination during storage (Candida wound infection). In three of 64 patients who received noncontaminated kidneys, posttransplant wound infections developed. No wound infections occurred in 35 patients who received prophylactic antibiotics, whereas four wound infections occurred in 48 patients without antibiotic coverage. It is concluded that, although microbial contamination of stored cadaver kidneys occurs commonly, it is not an important source of infection in renal transplant recipients."}
{"id": "PMID:25060", "title": "The Grimonster symposium on the occasion of the 50th anniversary of the first lumbar sympathectomy.", "content": "Under the auspices of the Belgian Surgical Society, a small group of American and European surgeons discussed in detail the place of lumbar sympathectomy in present day surgical practice. A consensus was reached concerning the physiologic effect, anatomical variations and indications for the operation. Conclusions included the questionable value of lumbar sympathectomy for treating intermittent claudication due to aortoiliac disease alone, its possible effectiveness when obliterative arterial disease is limited to the femoral popliteal segment, and its occasional beneficial effect when performed in conjunction with some reconstructive arterial operations.", "contents": "The Grimonster symposium on the occasion of the 50th anniversary of the first lumbar sympathectomy. Under the auspices of the Belgian Surgical Society, a small group of American and European surgeons discussed in detail the place of lumbar sympathectomy in present day surgical practice. A consensus was reached concerning the physiologic effect, anatomical variations and indications for the operation. Conclusions included the questionable value of lumbar sympathectomy for treating intermittent claudication due to aortoiliac disease alone, its possible effectiveness when obliterative arterial disease is limited to the femoral popliteal segment, and its occasional beneficial effect when performed in conjunction with some reconstructive arterial operations."}
{"id": "PMID:25061", "title": "Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolities in vitro and in vivo.", "content": "Rats were exposed to [1,2-14C] vinyl chloride. Liver RNA was isolated, hydrolyzed, and the nucleosides separated on Aminex-A-6. Besides the physiological bases and 1,N6-ethenoadenosine, radioactivity was also incorporated into 3,N4-ethenocytidine. Radioactive 3,N4-ethenocytidine moieties were also formed on incubation of polycytidylic acid with rat liver microsomes, NADPH and [14C] vinyl chloride. These alkylation mechanisms are consistent with the mutagenic and cancerogenic properties of vinyl chloride.", "contents": "Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolities in vitro and in vivo. Rats were exposed to [1,2-14C] vinyl chloride. Liver RNA was isolated, hydrolyzed, and the nucleosides separated on Aminex-A-6. Besides the physiological bases and 1,N6-ethenoadenosine, radioactivity was also incorporated into 3,N4-ethenocytidine. Radioactive 3,N4-ethenocytidine moieties were also formed on incubation of polycytidylic acid with rat liver microsomes, NADPH and [14C] vinyl chloride. These alkylation mechanisms are consistent with the mutagenic and cancerogenic properties of vinyl chloride."}
{"id": "PMID:25062", "title": "Studies of rat alkaline phosphatase I. Development of methods for detecting isoenzymes.", "content": "A manual system of various estimations of rat plasma alkaline phosphatase activity has been devised for small volumes of plasma which uses different inhibitors, compares the utilisation of two substrates and includes acrylamide gel electrophoresis. The different inhibitors etc. allow a degree of discrimination between alkaline phosphatase extracts of rat organs. The properties of isoenzymes, e.g. intestinal phosphatase, differ depending upon the environment in which they are studied. In conjunction, if necessary, with the methods described for the estimation of liver and intestinal alkaline phosphatase activity, it is hoped to use the system to discriminate between the isoenzymes present in the plasma alkaline phosphatase of rats in toxicological studies.", "contents": "Studies of rat alkaline phosphatase I. Development of methods for detecting isoenzymes. A manual system of various estimations of rat plasma alkaline phosphatase activity has been devised for small volumes of plasma which uses different inhibitors, compares the utilisation of two substrates and includes acrylamide gel electrophoresis. The different inhibitors etc. allow a degree of discrimination between alkaline phosphatase extracts of rat organs. The properties of isoenzymes, e.g. intestinal phosphatase, differ depending upon the environment in which they are studied. In conjunction, if necessary, with the methods described for the estimation of liver and intestinal alkaline phosphatase activity, it is hoped to use the system to discriminate between the isoenzymes present in the plasma alkaline phosphatase of rats in toxicological studies."}
{"id": "PMID:25057", "title": "[Experimental studies of the specificity and aspecificity of a beta-adrenolytic agent, bunitrolol (K\u00f6 1366)].", "content": "In basis of our experimental researches bunitrolol presented: a) beta-adrenolytic activity prevailingly at cardiac level (superior to propranolol and practolol) in respect to vascular, tracheal, bronchial, uterus, intestinal and metabolic level; b) beta-adrenergic intrinsic activity; c) local anesthetic activity; d) chinidino-like activity; e) antiarrhythmic activity; f) hypotensive activity with interferences at the level of vasomotor centres, of the barosensitive zones, of the renin secretion and of the purinergic periphery.", "contents": "[Experimental studies of the specificity and aspecificity of a beta-adrenolytic agent, bunitrolol (K\u00f6 1366)]. In basis of our experimental researches bunitrolol presented: a) beta-adrenolytic activity prevailingly at cardiac level (superior to propranolol and practolol) in respect to vascular, tracheal, bronchial, uterus, intestinal and metabolic level; b) beta-adrenergic intrinsic activity; c) local anesthetic activity; d) chinidino-like activity; e) antiarrhythmic activity; f) hypotensive activity with interferences at the level of vasomotor centres, of the barosensitive zones, of the renin secretion and of the purinergic periphery."}
{"id": "PMID:25058", "title": "[Experimental analysis of the cardiovascular effects of acebutolol, a drug with beta-adrenolytic activity].", "content": "In experiments at cardiovascular system level, acebutolol was found to possess beta-adrenolytic activity of cardioselective type associated with intrinsic beta-adrenergic, antiarrhythmic and anti-hypertensive activity. It was well tolerated systemically.", "contents": "[Experimental analysis of the cardiovascular effects of acebutolol, a drug with beta-adrenolytic activity]. In experiments at cardiovascular system level, acebutolol was found to possess beta-adrenolytic activity of cardioselective type associated with intrinsic beta-adrenergic, antiarrhythmic and anti-hypertensive activity. It was well tolerated systemically."}
{"id": "PMID:25063", "title": "Local injuries by accidental ingestion of corrosive substances by children.", "content": "Own data and analysis of previous publications show that situations where accidental ingestion of corrosive substances by children may have happened are frequent, but severe corrosive esophagitis leading to perforation or stricture formation is very rare. In case of suspected esophageal injury, esophagoscopy and glucocorticoid treatment become necessary. The evaluation of the initial symptoms in patients from our own material and from the literature indicates that all children with serious esophageal burns had one or more of the following symptoms: visible burns in the oral cavity, hypersalivation, retching, vomiting, retrosternal or epigastric pain, cardiovascular collaps, airway stenosis. Hence, children with an uncertain history of ingestion and without any of these symptoms need not be treated. After ingestion of liquid substances, but never of dry or granular products, lesions in the esophagus without accompanying burns in the oral cavity were observed. The evaluation of 1158 cases of accidental ingestions of several types of household products and a collection of data from the literature on the causticity of these substances shows that cleaners containing mainly detergents and phosphates (with pH values generally between 9 and 11), and household bleaches on sodium hypochlorite basis, are relatively harmless. Drain cleaners (NaOH), decalcifiers (formic acid) and detergents for automatic dish washing machines (metasilicates) are very caustic and are responsible for the majority of serious accidents in children.", "contents": "Local injuries by accidental ingestion of corrosive substances by children. Own data and analysis of previous publications show that situations where accidental ingestion of corrosive substances by children may have happened are frequent, but severe corrosive esophagitis leading to perforation or stricture formation is very rare. In case of suspected esophageal injury, esophagoscopy and glucocorticoid treatment become necessary. The evaluation of the initial symptoms in patients from our own material and from the literature indicates that all children with serious esophageal burns had one or more of the following symptoms: visible burns in the oral cavity, hypersalivation, retching, vomiting, retrosternal or epigastric pain, cardiovascular collaps, airway stenosis. Hence, children with an uncertain history of ingestion and without any of these symptoms need not be treated. After ingestion of liquid substances, but never of dry or granular products, lesions in the esophagus without accompanying burns in the oral cavity were observed. The evaluation of 1158 cases of accidental ingestions of several types of household products and a collection of data from the literature on the causticity of these substances shows that cleaners containing mainly detergents and phosphates (with pH values generally between 9 and 11), and household bleaches on sodium hypochlorite basis, are relatively harmless. Drain cleaners (NaOH), decalcifiers (formic acid) and detergents for automatic dish washing machines (metasilicates) are very caustic and are responsible for the majority of serious accidents in children."}
{"id": "PMID:25065", "title": "Poly(adenosine dephosphate ribose) metabolism and regulation of myocardial cell growth by oxygen.", "content": "Control of the rate of cardiac cell division by oxygen occurs most probably by altering the redox state of a control substance, e.g. NAD(+)right harpoon over left harpoonNADH. NAD(+) (and not NADH) forms poly(ADP-ribose), an inhibitor of DNA synthesis, in a reaction catalysed by poly(ADP-ribose) polymerase. Lower partial pressure of oxygen, which increases the rate of division, would shift NAD(+)-->NADH, decrease poly(ADP-ribose) synthesis, and increase DNA synthesis. Chick-embryo heart cells grown in culture in 20% O(2) (in which they divide more slowly than in 5% O(2)) did exhibit greater poly(ADP-ribose) polymerase activity (+83%, P<0.001) than when grown in 5% O(2). Reaction product was identified as poly(ADP-ribose) by its insensitivity to deoxyribonuclease, ribonuclease, NAD glycohydrolase, Pronase, trypsin and micrococcal nuclease, and by its complete digestion with snake-venom phosphodiesterase to phosphoribosyl-AMP and AMP. Isolation of these digestion products by Dowex 1 (formate form) column chromatography and paper chromatography allowed calculation of average poly(ADP-ribose) chain length, which was 15-26% greater in 20% than in 5% O(2). Thus in 20% O(2) the increase in poly(ADP-ribose) formation results from chain elongation. Formation of new chains also occurs, probably to an even greater degree than chain elongation. Additionally, poly(ADP-ribose) polymerase has very different K(m) and V(max.) values and pH optima in 20% and 5% O(2). These data suggest that poly(ADP-ribose) metabolism participates in the regulation of heart-cell division by O(2), probably by several different mechanisms.", "contents": "Poly(adenosine dephosphate ribose) metabolism and regulation of myocardial cell growth by oxygen. Control of the rate of cardiac cell division by oxygen occurs most probably by altering the redox state of a control substance, e.g. NAD(+)right harpoon over left harpoonNADH. NAD(+) (and not NADH) forms poly(ADP-ribose), an inhibitor of DNA synthesis, in a reaction catalysed by poly(ADP-ribose) polymerase. Lower partial pressure of oxygen, which increases the rate of division, would shift NAD(+)-->NADH, decrease poly(ADP-ribose) synthesis, and increase DNA synthesis. Chick-embryo heart cells grown in culture in 20% O(2) (in which they divide more slowly than in 5% O(2)) did exhibit greater poly(ADP-ribose) polymerase activity (+83%, P<0.001) than when grown in 5% O(2). Reaction product was identified as poly(ADP-ribose) by its insensitivity to deoxyribonuclease, ribonuclease, NAD glycohydrolase, Pronase, trypsin and micrococcal nuclease, and by its complete digestion with snake-venom phosphodiesterase to phosphoribosyl-AMP and AMP. Isolation of these digestion products by Dowex 1 (formate form) column chromatography and paper chromatography allowed calculation of average poly(ADP-ribose) chain length, which was 15-26% greater in 20% than in 5% O(2). Thus in 20% O(2) the increase in poly(ADP-ribose) formation results from chain elongation. Formation of new chains also occurs, probably to an even greater degree than chain elongation. Additionally, poly(ADP-ribose) polymerase has very different K(m) and V(max.) values and pH optima in 20% and 5% O(2). These data suggest that poly(ADP-ribose) metabolism participates in the regulation of heart-cell division by O(2), probably by several different mechanisms."}
{"id": "PMID:25066", "title": "Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk.", "content": "1. The neuraminidase activity of homogenates of the mucosa of the middle and distal thirds of the small intestine of rats increased about 5-fold between birth and 4 to 8 days of age, and then gradually declined to the much lower adult activity by 24 days. No comparable changes occurred in the proximal third. 2. In 8-day-old rats, the neuraminidase activity of the middle and distal thirds of the small intestine was about 10 times greater than that of the proximal third, 20 times greater than that of the colon and at least 100 times greater than that of the liver, brain, gastric mucosa or pancreas. 3. In all other species investigated (mice, rabbits, cats and guinea pigs), the neuraminidase activity of the middle and distal thirds of the small intestine was greater in suckling animals than in adults. 4. The sialic acid content of rat milk increased about 2-fold between birth and 8 days post partum and then declined. 5. There was a highly significant positive correlation between the intestinal neuraminidase activity of suckling animals of various species and ages and the sialic acid content of milk obtained from the corresponding species and stage of lactation. 6. It is suggested that the intestinal neuraminidase of suckling mammals functions primarily to remove sialic acid from various components of milk, thus providing sialic acid for the synthesis of sialoglycoproteins and gangliosides by the young.", "contents": "Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk. 1. The neuraminidase activity of homogenates of the mucosa of the middle and distal thirds of the small intestine of rats increased about 5-fold between birth and 4 to 8 days of age, and then gradually declined to the much lower adult activity by 24 days. No comparable changes occurred in the proximal third. 2. In 8-day-old rats, the neuraminidase activity of the middle and distal thirds of the small intestine was about 10 times greater than that of the proximal third, 20 times greater than that of the colon and at least 100 times greater than that of the liver, brain, gastric mucosa or pancreas. 3. In all other species investigated (mice, rabbits, cats and guinea pigs), the neuraminidase activity of the middle and distal thirds of the small intestine was greater in suckling animals than in adults. 4. The sialic acid content of rat milk increased about 2-fold between birth and 8 days post partum and then declined. 5. There was a highly significant positive correlation between the intestinal neuraminidase activity of suckling animals of various species and ages and the sialic acid content of milk obtained from the corresponding species and stage of lactation. 6. It is suggested that the intestinal neuraminidase of suckling mammals functions primarily to remove sialic acid from various components of milk, thus providing sialic acid for the synthesis of sialoglycoproteins and gangliosides by the young."}
{"id": "PMID:25070", "title": "[Reaction kinetic studies on the formation of n-nitrosoephedrine in vitro and in vivo (author's transl)].", "content": "N-Nitrosoephedrine was synthesized at a high yield (greater than 90%). The influence of pH on the reaction process (ephedrine sulfate + nitrous acid in hydrochloric acid) was investigated and the pH-optimum determined. Furthermore the influence of coffee, ascorbic acid, citric acid, cyclamate/saccharin (10:1), smoke condensate of cigarettes, glucose and ethanol on the reaction process was also determined. The tests with animals (rats) showed that N-nitrosoephedrine could be detected in serum after the oral application of ephedrine sulfate and sodium nitrite.", "contents": "[Reaction kinetic studies on the formation of n-nitrosoephedrine in vitro and in vivo (author's transl)]. N-Nitrosoephedrine was synthesized at a high yield (greater than 90%). The influence of pH on the reaction process (ephedrine sulfate + nitrous acid in hydrochloric acid) was investigated and the pH-optimum determined. Furthermore the influence of coffee, ascorbic acid, citric acid, cyclamate/saccharin (10:1), smoke condensate of cigarettes, glucose and ethanol on the reaction process was also determined. The tests with animals (rats) showed that N-nitrosoephedrine could be detected in serum after the oral application of ephedrine sulfate and sodium nitrite."}
{"id": "PMID:25071", "title": "Clinical experiments with the new oral long-acting neuroleptic clopimozide (R 29 764).", "content": "A pilot study with the new oral long-acting neuroleptic agent clopimozide, a diphenylbutylpiperidine derivative, has been reported. 30 female patients, only 20 of whom completed the trial, were treated with dosages of between 5 and 35 mg. The treatment comprised four periods in which the maximum tolerated daily dosage, the optimal weekly dosage (mean: 20.25 mg), the maximum tolerated weekly dosage and the optimal daily dosage were to be determined. In 10 patients plasma levels were determined with the radio-immunological method. The product exhibited a marked effect on schizophrenic target symptoms (significant at the 0.001 and 0.01 levels), of at least one week's duration, with an absence of sedation and a low degree of extrapyramidal side-effects. Clopimozide appears to be particularly suitable for the neuroleptic long-term treatment of compensated schizophrenic patients with insight into their disease.", "contents": "Clinical experiments with the new oral long-acting neuroleptic clopimozide (R 29 764). A pilot study with the new oral long-acting neuroleptic agent clopimozide, a diphenylbutylpiperidine derivative, has been reported. 30 female patients, only 20 of whom completed the trial, were treated with dosages of between 5 and 35 mg. The treatment comprised four periods in which the maximum tolerated daily dosage, the optimal weekly dosage (mean: 20.25 mg), the maximum tolerated weekly dosage and the optimal daily dosage were to be determined. In 10 patients plasma levels were determined with the radio-immunological method. The product exhibited a marked effect on schizophrenic target symptoms (significant at the 0.001 and 0.01 levels), of at least one week's duration, with an absence of sedation and a low degree of extrapyramidal side-effects. Clopimozide appears to be particularly suitable for the neuroleptic long-term treatment of compensated schizophrenic patients with insight into their disease."}
{"id": "PMID:25075", "title": "Beta-blockers and asthma.", "content": "In a single-blind, randomised, crossover study in 10 asthmatic patients, the effects of approximately equipotent oral doses of 3 cardioselective beta-blockers-atenolol (100 mg), metoprolol (100 mg), and acebutolol (300 mg)-and 4 non-cardioselective beta-blockers-proranolol (100 mg), oxprenolol (100 mg), pindolol (5 mg), and timolol (10 mg) upon FEV1 were compared. All drugs, except pindolol, produced a significant reduction in standing pulse rate and prevented an increase in heart rate after inhaled isoprenaline (1500 microgram). All drugs caused a fall in FEV1 but only atenolol did not differ significantly from placebo in this respect. The bronchodilator response to inhaled isoprenaline was blocked by the 4 non-cardioselective drugs; the 3 cardioselective agents permitted some bronchodilatation, but only atenolol did not differ from placebo.", "contents": "Beta-blockers and asthma. In a single-blind, randomised, crossover study in 10 asthmatic patients, the effects of approximately equipotent oral doses of 3 cardioselective beta-blockers-atenolol (100 mg), metoprolol (100 mg), and acebutolol (300 mg)-and 4 non-cardioselective beta-blockers-proranolol (100 mg), oxprenolol (100 mg), pindolol (5 mg), and timolol (10 mg) upon FEV1 were compared. All drugs, except pindolol, produced a significant reduction in standing pulse rate and prevented an increase in heart rate after inhaled isoprenaline (1500 microgram). All drugs caused a fall in FEV1 but only atenolol did not differ significantly from placebo in this respect. The bronchodilator response to inhaled isoprenaline was blocked by the 4 non-cardioselective drugs; the 3 cardioselective agents permitted some bronchodilatation, but only atenolol did not differ from placebo."}
{"id": "PMID:25076", "title": "Comparison of diazepam and flunitrazepam for sedation during local anaesthesia for bronchoscopy.", "content": "Diazepam and flunitrazepam were compared as amnesic and sedative adjuncts to local anaesthesia for diagnostic bronchoscopy in 92 patients. After local anaesthesia of the pharynx, larynx and trachea with lignocaine, atropine plus diazepam of flunitrazepam was injected i.v. The co-operation of the patients and the technical circumstances under which the bronchoscopy was performed were good in each group. None of the treatments significantly modified arterial pressure or heart rate. Two hours after the injection, flunitrazepam 0.01 mg kg-1 more frequently caused amnesia for pictures shown to the patients during the first 15 min after injection (failure to recall 42--75%, and for bronchoscopy 67%), than did diazepam 0.125 mg kg-1 (failure to recall 21--67%; bronchoscopy 38%). Double doses of the drugs caused amnesic actions similar to those of flunitrazepam 0.01 mg kg-1. When failure to recall was assessed on the following day, 29% and 5% of the patients remembered bronchoscopy after flunitrazepam 0.01 and 0.02 mg kg-1 respectively; after diazepam 0.125 and 0.25 mg kg-1 the corresponding percentages was 59% and 30% (P less than 0.05% v. fluintrazepam). The ability to stand and walk on a stright line was similar after the smaller doses of both drugs, but after the larger doses recovery was slower after flunitrazepam. Psychomotor performance was still distinctly impaired 2 h after the injection of the larger doses.", "contents": "Comparison of diazepam and flunitrazepam for sedation during local anaesthesia for bronchoscopy. Diazepam and flunitrazepam were compared as amnesic and sedative adjuncts to local anaesthesia for diagnostic bronchoscopy in 92 patients. After local anaesthesia of the pharynx, larynx and trachea with lignocaine, atropine plus diazepam of flunitrazepam was injected i.v. The co-operation of the patients and the technical circumstances under which the bronchoscopy was performed were good in each group. None of the treatments significantly modified arterial pressure or heart rate. Two hours after the injection, flunitrazepam 0.01 mg kg-1 more frequently caused amnesia for pictures shown to the patients during the first 15 min after injection (failure to recall 42--75%, and for bronchoscopy 67%), than did diazepam 0.125 mg kg-1 (failure to recall 21--67%; bronchoscopy 38%). Double doses of the drugs caused amnesic actions similar to those of flunitrazepam 0.01 mg kg-1. When failure to recall was assessed on the following day, 29% and 5% of the patients remembered bronchoscopy after flunitrazepam 0.01 and 0.02 mg kg-1 respectively; after diazepam 0.125 and 0.25 mg kg-1 the corresponding percentages was 59% and 30% (P less than 0.05% v. fluintrazepam). The ability to stand and walk on a stright line was similar after the smaller doses of both drugs, but after the larger doses recovery was slower after flunitrazepam. Psychomotor performance was still distinctly impaired 2 h after the injection of the larger doses."}
{"id": "PMID:25077", "title": "Fazadinium in anaesthesia.", "content": "The clinical use of the neuromuscular blocking agent fazadinium was investigated in a survey of 500 patients. Rapid conditions for tracheal intubation followed by excellent relaxation and easy antagonism were obtained. It is suggested that these findings commend it as an alternative to suxamethonium. Tachycardia appeared to be the only disadvantage associated with its use.", "contents": "Fazadinium in anaesthesia. The clinical use of the neuromuscular blocking agent fazadinium was investigated in a survey of 500 patients. Rapid conditions for tracheal intubation followed by excellent relaxation and easy antagonism were obtained. It is suggested that these findings commend it as an alternative to suxamethonium. Tachycardia appeared to be the only disadvantage associated with its use."}
{"id": "PMID:25078", "title": "Acid hydrolases in blister fluid. I. Characterization and quantification of acid phosphatase.", "content": "Acid phosphatase has been characterized and quantified in human suction blister fluid, interstitial fluid and serum. The acid phosphatases of suction blister fluid and serum showed differences in their pH activity curves, Michaelis-Menton constants, heat stabilities and sensitivities to inhibition by tartrate and fluoride. The behaviour of the interstitial fluid enzyme was intermediate between these two. The levels of activity in blister fluid and serum were very similar, both being more than twice that of interstitial fluid. These results suggest that the acid phosphatase activity in suction blister fluid is derived largely from the overlying epidermis rather than from serum.", "contents": "Acid hydrolases in blister fluid. I. Characterization and quantification of acid phosphatase. Acid phosphatase has been characterized and quantified in human suction blister fluid, interstitial fluid and serum. The acid phosphatases of suction blister fluid and serum showed differences in their pH activity curves, Michaelis-Menton constants, heat stabilities and sensitivities to inhibition by tartrate and fluoride. The behaviour of the interstitial fluid enzyme was intermediate between these two. The levels of activity in blister fluid and serum were very similar, both being more than twice that of interstitial fluid. These results suggest that the acid phosphatase activity in suction blister fluid is derived largely from the overlying epidermis rather than from serum."}
{"id": "PMID:25079", "title": "Acid hydrolases in blister fluid. II. Characterization and quantification of glycoside hydrolases.", "content": "Seven glycoside hydrolases have been investigated in suction blister fluid, interstitial fluid and in serum. Six of these have been characterized; no differences could be demonstrated between the corresponding enzymes from the various sources. The remaining enzyme (beta-glucosidase) was not found. Quantitative data suggest that 2 enzymes (beta-acetylglucosaminidase and beta-glucuronidase) diffuse freely from the epidermis into blister fluid, whereas 4 (alpha-glucosidase, alpha- and beta-galactosidase and alpha-mannosidase) are almost entirely retained in the roof of the bulla.", "contents": "Acid hydrolases in blister fluid. II. Characterization and quantification of glycoside hydrolases. Seven glycoside hydrolases have been investigated in suction blister fluid, interstitial fluid and in serum. Six of these have been characterized; no differences could be demonstrated between the corresponding enzymes from the various sources. The remaining enzyme (beta-glucosidase) was not found. Quantitative data suggest that 2 enzymes (beta-acetylglucosaminidase and beta-glucuronidase) diffuse freely from the epidermis into blister fluid, whereas 4 (alpha-glucosidase, alpha- and beta-galactosidase and alpha-mannosidase) are almost entirely retained in the roof of the bulla."}
{"id": "PMID:25080", "title": "Metabolic changes associated with intake by cows of complete diets containing straw and concentrates in different proportions.", "content": "1. Pelleted diets containing concentrates and 0, 200, 400 or 600 g chopped straw/kg were fed ad lib, for 5 h daily to four cows. Concentrations of various energy-yielding metabolites were measured in samples of rumen fluid and jugular blood taken before feeding and at intervals after food was offered. 2. After feeding, the pH of rumen fluid decreased rapidly and the total concentration of volatile fatty acids (VFA) increased; the changes were greatest in the diet containing no roughage. The changes were essentially complete by 135 min at approximately the time feeding stopped. Rumen lactate concentrations were always low and increased significantly only in cows given no roughage. 3. There were highly significant relationships between the peak rumen acetate concentration after a meal and the apparent digestibility of the dry matter of that meal, and the amount of material in the rumen at the end of a meal. The latter relationship resulted in there being no difference between treatments in the total amount of acetate present in the rumen after feeding. 4. In the blood, concentrations of acetate, propionate, beta-hydroxybutyrate (BHB) and lactate all increased after feeding. The increase was prolonged and maximum values were rarely reached before 4-5 h. The highest concentrations of acetate and BHB were found in cows given 20 g roughage/kg and were twice as great as those in cows given no roughage; lower concentrations were found in cows given 400 or 600 g roughage/kg. This information, together with the rumen concentrations of acetate and butyrate, was interpreted as indicating an inhibition of VFA absorption from the rumen of cows given no roughage. 5. Plasma glucose concentrations decreased rapidly for 4 h after feeding, the decrease being greatest in cows given 200 g roughage/kg. Non-esterified fatty acid concentrations also decreased after feeding 200 and 0 g roughage/kg rations, but concentrations were not high at any time. 6. It is concluded that chemical changes in the rumen correspond to feeding behaviour much more closely than changes in blood and therefore any chemostatic regulation of food intake probably occurs at the former site, with acetate playing a major role. Monitoring energy balance at tissue level is likely to be mediated hormonally, with insulin an important factor.", "contents": "Metabolic changes associated with intake by cows of complete diets containing straw and concentrates in different proportions. 1. Pelleted diets containing concentrates and 0, 200, 400 or 600 g chopped straw/kg were fed ad lib, for 5 h daily to four cows. Concentrations of various energy-yielding metabolites were measured in samples of rumen fluid and jugular blood taken before feeding and at intervals after food was offered. 2. After feeding, the pH of rumen fluid decreased rapidly and the total concentration of volatile fatty acids (VFA) increased; the changes were greatest in the diet containing no roughage. The changes were essentially complete by 135 min at approximately the time feeding stopped. Rumen lactate concentrations were always low and increased significantly only in cows given no roughage. 3. There were highly significant relationships between the peak rumen acetate concentration after a meal and the apparent digestibility of the dry matter of that meal, and the amount of material in the rumen at the end of a meal. The latter relationship resulted in there being no difference between treatments in the total amount of acetate present in the rumen after feeding. 4. In the blood, concentrations of acetate, propionate, beta-hydroxybutyrate (BHB) and lactate all increased after feeding. The increase was prolonged and maximum values were rarely reached before 4-5 h. The highest concentrations of acetate and BHB were found in cows given 20 g roughage/kg and were twice as great as those in cows given no roughage; lower concentrations were found in cows given 400 or 600 g roughage/kg. This information, together with the rumen concentrations of acetate and butyrate, was interpreted as indicating an inhibition of VFA absorption from the rumen of cows given no roughage. 5. Plasma glucose concentrations decreased rapidly for 4 h after feeding, the decrease being greatest in cows given 200 g roughage/kg. Non-esterified fatty acid concentrations also decreased after feeding 200 and 0 g roughage/kg rations, but concentrations were not high at any time. 6. It is concluded that chemical changes in the rumen correspond to feeding behaviour much more closely than changes in blood and therefore any chemostatic regulation of food intake probably occurs at the former site, with acetate playing a major role. Monitoring energy balance at tissue level is likely to be mediated hormonally, with insulin an important factor."}
{"id": "PMID:25081", "title": "On the measurement of pH in Escherichia coli by 31P nuclear magnetic resonance.", "content": "The 31P high resolution NMR spectra of concentrated suspensions of Escherichia coli cells have been measured at 145.8 MHz. The position of the orthophosphate resonance is used as a measure of internal and external pH. In accord with Paddan, Zilberstein and Rottenberg ((1976) Eur. J. Biochem. 63, 533--541) it is shown that when properly energized the internal pH is 7.5 +/- 0.1. By synchronizing the NMR data acquisition with 3-s bursts of O2 it is possible to measure the internal pH with a time resolution of about 1 s. It is shown that at 20 degrees C the pH remains constant for times longer than 15 s after the oxygen is discontinued and it decays in several minutes.", "contents": "On the measurement of pH in Escherichia coli by 31P nuclear magnetic resonance. The 31P high resolution NMR spectra of concentrated suspensions of Escherichia coli cells have been measured at 145.8 MHz. The position of the orthophosphate resonance is used as a measure of internal and external pH. In accord with Paddan, Zilberstein and Rottenberg ((1976) Eur. J. Biochem. 63, 533--541) it is shown that when properly energized the internal pH is 7.5 +/- 0.1. By synchronizing the NMR data acquisition with 3-s bursts of O2 it is possible to measure the internal pH with a time resolution of about 1 s. It is shown that at 20 degrees C the pH remains constant for times longer than 15 s after the oxygen is discontinued and it decays in several minutes."}
{"id": "PMID:25082", "title": "A study of H+ transport in gastric microsomal vesicles using fluorescent probes.", "content": "Fluorescent amines, 9-aminoacridine, acridine orange and quinacrine, were used as probes for a pH gradient (deltapH) across gastric microsomal vesicles. Analysis of probe uptake data indicates that 9-aminoacridine distributes across the membrane as a weak base in accordance with the deltapH. On the other hand, acridine orange and quinacrine show characteristics of binding to membrane sites in addition to the accumulation in response to deltapH. A discussion of the advantages and limitations of the probes is presented. Application of these probes to pig gastric microsomal vesicles indicates that that K+-stimulated ATPase is responsible for the transport of H+ into the vesicles and thus develops a deltapH across the membrane. The deltapH generated by the K+-ATPase has a definite requirement for internal K+. The proton gradient can be discharged slowly after ATP depletion or rapidly either by detergent disruption of the vesicles or by increasing their leakiness using both H+ and K+ ionophores. On the other hand, the sole use of the K+ ionophore, valinomycin, stimulates the ATP-induced formation of deltapH by increasing the availability of K+ to internal sites. This stimulation by valinomycin requires the presence of permeable anions like Cl-. Analysis of the Cl- requirement indicates that in the presence of valinomycin the net effect is the accumulation of HCl inside the gastric vesicles. With an external pH of 7.0, the ATP-generated deltapH was calculated to be from 4 to 4.5 pH units. The results are consistent with the hypothesis that the K+-stimulated ATPase drives a K+/H+ exchange across the gastric vesicles. Since other lines of evidence suggest that these gastric microsomes are derived from the tubulovesicular system of the oxyntic cell, the participation of the ATP-driven transport processes in gastric HCl secretion is of interest.", "contents": "A study of H+ transport in gastric microsomal vesicles using fluorescent probes. Fluorescent amines, 9-aminoacridine, acridine orange and quinacrine, were used as probes for a pH gradient (deltapH) across gastric microsomal vesicles. Analysis of probe uptake data indicates that 9-aminoacridine distributes across the membrane as a weak base in accordance with the deltapH. On the other hand, acridine orange and quinacrine show characteristics of binding to membrane sites in addition to the accumulation in response to deltapH. A discussion of the advantages and limitations of the probes is presented. Application of these probes to pig gastric microsomal vesicles indicates that that K+-stimulated ATPase is responsible for the transport of H+ into the vesicles and thus develops a deltapH across the membrane. The deltapH generated by the K+-ATPase has a definite requirement for internal K+. The proton gradient can be discharged slowly after ATP depletion or rapidly either by detergent disruption of the vesicles or by increasing their leakiness using both H+ and K+ ionophores. On the other hand, the sole use of the K+ ionophore, valinomycin, stimulates the ATP-induced formation of deltapH by increasing the availability of K+ to internal sites. This stimulation by valinomycin requires the presence of permeable anions like Cl-. Analysis of the Cl- requirement indicates that in the presence of valinomycin the net effect is the accumulation of HCl inside the gastric vesicles. With an external pH of 7.0, the ATP-generated deltapH was calculated to be from 4 to 4.5 pH units. The results are consistent with the hypothesis that the K+-stimulated ATPase drives a K+/H+ exchange across the gastric vesicles. Since other lines of evidence suggest that these gastric microsomes are derived from the tubulovesicular system of the oxyntic cell, the participation of the ATP-driven transport processes in gastric HCl secretion is of interest."}
{"id": "PMID:25083", "title": "NMR kinetic studies of the ionophore X-537A-mediated transport of manganous ions across phospholipid bilayers.", "content": "Nuclear magnetic resonance spectroscopy has been applied as a method for studying manganous ions transport across the membrane of phosphatidylcholine vesicles. The rates of the ionophore X-537A (lasalocid A)-mediated Mn2+ transport have been measured as a function of ionophore concentration, pH of the vesicle suspension, and temperature. The translocation was found to occur via a neutral complex composed of one manganous ion bound in two ionized X-537A molecules (Mn X2). The activation energy for the overall transport process was determined to be 22 +/- 5 kcal/mol. Also a pKa of 5.0 +/- 0.2 was determined for the ionophore acid dissociation equilibrium in the vesicle suspension.", "contents": "NMR kinetic studies of the ionophore X-537A-mediated transport of manganous ions across phospholipid bilayers. Nuclear magnetic resonance spectroscopy has been applied as a method for studying manganous ions transport across the membrane of phosphatidylcholine vesicles. The rates of the ionophore X-537A (lasalocid A)-mediated Mn2+ transport have been measured as a function of ionophore concentration, pH of the vesicle suspension, and temperature. The translocation was found to occur via a neutral complex composed of one manganous ion bound in two ionized X-537A molecules (Mn X2). The activation energy for the overall transport process was determined to be 22 +/- 5 kcal/mol. Also a pKa of 5.0 +/- 0.2 was determined for the ionophore acid dissociation equilibrium in the vesicle suspension."}
{"id": "PMID:25084", "title": "Effects of pH on beta-hydroxybutyrate transport in rat erythrocytes and thymocytes.", "content": "Entry of beta-hydroxybutyrate into erythrocytes and thymocytes is facilitated by a carrier (C), as judged from temperature dependence, saturation kinetics, stereospecificity, competition with lactate and pyruvate, and inhibition by moderate concentrations of methylisobutylxanthine, phloretin, or alpha-cyanocinnamate. We studied the dependence of influx and efflux on internal and external pH and [beta-hydroxybutyrate]. Lowering external pH from 8.0 to 7.3 to 6.6 enhanced influx into erythrocytes by lowering entry Km from 29 to 16 to 10 mM, entry V being independent of external pH. Lowering external pH inhibited efflux. At low external pH, external beta-hydroxybutyrate enhanced efflux slightly. At high external pH, external beta-hydroxybutyrate inhibited efflux. Internal acidification inhibited influx and internal alkalization enhanced influx. Internal beta-hydroxybutyrate (betaHB) enhanced influx more in acidified than alkalized cells. These data are compatible with coupled betaHB-/OH- exchange, betaHB- and OH- competing for influx, C:OH- moving faster than C: betaHB-, empty C being immobile. They are also compatible with coupled betaHB-/H+ copermeation, empty C moving inward faster than H+:C:betaHB-, H+:C being immobile, and C:betaHB- (without H+) being so unstable as not to be formed in significant amounts (relative to C, H+:C, and H+:C:betaHB-).", "contents": "Effects of pH on beta-hydroxybutyrate transport in rat erythrocytes and thymocytes. Entry of beta-hydroxybutyrate into erythrocytes and thymocytes is facilitated by a carrier (C), as judged from temperature dependence, saturation kinetics, stereospecificity, competition with lactate and pyruvate, and inhibition by moderate concentrations of methylisobutylxanthine, phloretin, or alpha-cyanocinnamate. We studied the dependence of influx and efflux on internal and external pH and [beta-hydroxybutyrate]. Lowering external pH from 8.0 to 7.3 to 6.6 enhanced influx into erythrocytes by lowering entry Km from 29 to 16 to 10 mM, entry V being independent of external pH. Lowering external pH inhibited efflux. At low external pH, external beta-hydroxybutyrate enhanced efflux slightly. At high external pH, external beta-hydroxybutyrate inhibited efflux. Internal acidification inhibited influx and internal alkalization enhanced influx. Internal beta-hydroxybutyrate (betaHB) enhanced influx more in acidified than alkalized cells. These data are compatible with coupled betaHB-/OH- exchange, betaHB- and OH- competing for influx, C:OH- moving faster than C: betaHB-, empty C being immobile. They are also compatible with coupled betaHB-/H+ copermeation, empty C moving inward faster than H+:C:betaHB-, H+:C being immobile, and C:betaHB- (without H+) being so unstable as not to be formed in significant amounts (relative to C, H+:C, and H+:C:betaHB-)."}
{"id": "PMID:25086", "title": "The kinetics and equilibria of squirrel-fish hemoglobin. A Root effect hemoglobin complicated by large subunit heterogeneity.", "content": "The functional properties of squirrel-fish hemoglobin have been measured by studying ligand binding equilibria and kinetics. The results show that squirrel-fish hemoglobin has a Root effect with a corresponding stabilization of the low affinity state. The properties of this state are pH dependent even in the absence of cooperativity. The effect of ATP shifts the overall ligant affinity towards the low affinity state and is characteristic of the allosteric effect caused by organic phosphates. Under pH and ATP conditions favoring the low affinity conformational state, a 10-fold difference in the binding kinetics of carbon monoxide to the alpha and beta subunits is observed.", "contents": "The kinetics and equilibria of squirrel-fish hemoglobin. A Root effect hemoglobin complicated by large subunit heterogeneity. The functional properties of squirrel-fish hemoglobin have been measured by studying ligand binding equilibria and kinetics. The results show that squirrel-fish hemoglobin has a Root effect with a corresponding stabilization of the low affinity state. The properties of this state are pH dependent even in the absence of cooperativity. The effect of ATP shifts the overall ligant affinity towards the low affinity state and is characteristic of the allosteric effect caused by organic phosphates. Under pH and ATP conditions favoring the low affinity conformational state, a 10-fold difference in the binding kinetics of carbon monoxide to the alpha and beta subunits is observed."}
{"id": "PMID:25087", "title": "Circular dichroism of metallothioneins. A structural approach.", "content": "A comprehensive study on circular dichroism of metallothioneins containing Zn, Cd and Cu was carried out. The contributions of the metals, the sulphur and the polypeptide chain to the observed Cotton effects was shown. From the pH dependency of the extrinsic Cotton effects which are due to the metal-thiolate chromophore the stability of the metal clusters was found to decrease in the order Cu greater than Cd greater than Zn. The pH values corresponding to the dissociation of half of the bound metal ions are 0.44 for Cu-thionein, 3.05 for Cd-thionein and 4.6 for Zn-thionein. The extrinsic Cotton effects of Cd, Zn-thioneins of varying Cd to Zn ratio could be simulated using the difference circular dichroic spectra of Cd-thionein (bands at 227, 242.5 and 262 nm), Zn-thionein (bands at 225 and 244 nm) and the circular dichroic spectrum of cysteine-thionein (band at 200 nm, shoulder at 225 nm). Since during the dissociation of the metals the circular dichroic spectra exhibited changes only in amplitude and not in shape we can conclude that the dissociation of the metal ions involves the complete sequential degradation of metal clusters. In the near-ultraviolet region the metal-free proteins show only Cotton effects attributable to a disulphide chromophore. Thus Cotton bands are observed for cystine-thionein at 282.5 and 260 nm. From the intrinsic circular dichroism of Cd- and Zn-thionein (negative Cotton effect at 200 nm, shoulder at 225 nm) it follows that the protein conformation consists of less than 5% helical or pleated sheet structure and therefore has to be classified as unordered structure or \"fixed\" random coil", "contents": "Circular dichroism of metallothioneins. A structural approach. A comprehensive study on circular dichroism of metallothioneins containing Zn, Cd and Cu was carried out. The contributions of the metals, the sulphur and the polypeptide chain to the observed Cotton effects was shown. From the pH dependency of the extrinsic Cotton effects which are due to the metal-thiolate chromophore the stability of the metal clusters was found to decrease in the order Cu greater than Cd greater than Zn. The pH values corresponding to the dissociation of half of the bound metal ions are 0.44 for Cu-thionein, 3.05 for Cd-thionein and 4.6 for Zn-thionein. The extrinsic Cotton effects of Cd, Zn-thioneins of varying Cd to Zn ratio could be simulated using the difference circular dichroic spectra of Cd-thionein (bands at 227, 242.5 and 262 nm), Zn-thionein (bands at 225 and 244 nm) and the circular dichroic spectrum of cysteine-thionein (band at 200 nm, shoulder at 225 nm). Since during the dissociation of the metals the circular dichroic spectra exhibited changes only in amplitude and not in shape we can conclude that the dissociation of the metal ions involves the complete sequential degradation of metal clusters. In the near-ultraviolet region the metal-free proteins show only Cotton effects attributable to a disulphide chromophore. Thus Cotton bands are observed for cystine-thionein at 282.5 and 260 nm. From the intrinsic circular dichroism of Cd- and Zn-thionein (negative Cotton effect at 200 nm, shoulder at 225 nm) it follows that the protein conformation consists of less than 5% helical or pleated sheet structure and therefore has to be classified as unordered structure or \"fixed\" random coil"}
{"id": "PMID:25088", "title": "Changes in structure and hydrophobic surface properties of beta-lactoglobulin determined by partition in aqueous two-phase polymeric systems.", "content": "The non-polar surface properties of beta-lactoglobulin and especially its interaction with poly(ethylene glycol)-bound palmitate has been studied as a function of pH, temperature and protein concentration. The maximum interaction between beta-lactoglobulin and polymer-bound palmitate occurs at pH 4.3 and pH 7.8. The change in conformation of beta-lactoglobulin around pH 7.5 seems to involve exposure of apolar amino acids to the solvent which results in an increased affinity for hydrocarbons. This is contrary to the situation at pH 4.8--6.0 where the corresponding change in conformation does not affect the protein-hydrocarbon interaction. The results suggest that partition studies in an aqueous two-phase system is a very useful tool to detect changes in conformation and aggregation and to characterize the corresponding hydrophobic surface properties of a protein.", "contents": "Changes in structure and hydrophobic surface properties of beta-lactoglobulin determined by partition in aqueous two-phase polymeric systems. The non-polar surface properties of beta-lactoglobulin and especially its interaction with poly(ethylene glycol)-bound palmitate has been studied as a function of pH, temperature and protein concentration. The maximum interaction between beta-lactoglobulin and polymer-bound palmitate occurs at pH 4.3 and pH 7.8. The change in conformation of beta-lactoglobulin around pH 7.5 seems to involve exposure of apolar amino acids to the solvent which results in an increased affinity for hydrocarbons. This is contrary to the situation at pH 4.8--6.0 where the corresponding change in conformation does not affect the protein-hydrocarbon interaction. The results suggest that partition studies in an aqueous two-phase system is a very useful tool to detect changes in conformation and aggregation and to characterize the corresponding hydrophobic surface properties of a protein."}
{"id": "PMID:25089", "title": "Influence of phosphate ligands in abolishing the conformational difference between ribonuclease A and its acid-denatured derivative.", "content": "The initial structural alteration of RNAase A due to acid denaturation (0.5 N HCl, 30 degrees C) that accompanies deamidation (without altering enzymic activity) has been dectected by spectrophotometric titration, fluorescence and ORD/CD measurements. It is shown that acid treated RNAase A has an altered conformation at neutral pH, 25 degrees C. This is characterized by the increased accessibility of buried tyrosine residue(s) towards the solvent. The most altered conformation of RNAase A is found in the 10 h acid-treated derivative. This has about 1.5 additional exposed tyrosine residues and a lesser amount of secondary structure than RNAase A. All three methods (titration, fluorescence and CD) established that the structural transition of RNAase A is biphasic. The first phase occurs within 1 h and the resulting subtle conformational change is constant up to 7 h. Following this, after the release of 0.55 mol of ammonia, the major conformational change begins. The altered conformation of the acid-denatured RNAase A could be reversed completely to the native state through a conformational change induced by substrate analogs like 2'- or 3'-CMP. Thus the monodeamidated derivative isolated from the acid-denatured RNAase A by phosphate is very similar to RNAase A in over-all conformation. The results suggest the possibility of flexibility in the RNAase A molecule that does not affect its catalytic activity, as probed through the tyrosine residues.", "contents": "Influence of phosphate ligands in abolishing the conformational difference between ribonuclease A and its acid-denatured derivative. The initial structural alteration of RNAase A due to acid denaturation (0.5 N HCl, 30 degrees C) that accompanies deamidation (without altering enzymic activity) has been dectected by spectrophotometric titration, fluorescence and ORD/CD measurements. It is shown that acid treated RNAase A has an altered conformation at neutral pH, 25 degrees C. This is characterized by the increased accessibility of buried tyrosine residue(s) towards the solvent. The most altered conformation of RNAase A is found in the 10 h acid-treated derivative. This has about 1.5 additional exposed tyrosine residues and a lesser amount of secondary structure than RNAase A. All three methods (titration, fluorescence and CD) established that the structural transition of RNAase A is biphasic. The first phase occurs within 1 h and the resulting subtle conformational change is constant up to 7 h. Following this, after the release of 0.55 mol of ammonia, the major conformational change begins. The altered conformation of the acid-denatured RNAase A could be reversed completely to the native state through a conformational change induced by substrate analogs like 2'- or 3'-CMP. Thus the monodeamidated derivative isolated from the acid-denatured RNAase A by phosphate is very similar to RNAase A in over-all conformation. The results suggest the possibility of flexibility in the RNAase A molecule that does not affect its catalytic activity, as probed through the tyrosine residues."}
{"id": "PMID:25090", "title": "Physicochemical properties of cartilage proteoglycans extracted by lanthanum chloride.", "content": "Bovine nasal cartilage was extracted with 0.5 M LaCl3 and the extract then diluted with nine volumes of water. The resulting precipitated (PLaCl3) contained the proteoglycan subunits, together with minor protein components, but was essentially free from hyaluronic acid. The properties of PLaCl3 were investigated by chemical analysis, electrophoresis, viscometry and analytical ultracentrifugation, and the results compared with those for proteoglycan obtained by caesium chloride density gradient centrifugation of 2 M CaCl2 cartilage extracts. Proteoglycan subunits (A1D1) prepared from PLaCl3 showed identical properties to those obtained from other high ionic strength cartilage extracts.", "contents": "Physicochemical properties of cartilage proteoglycans extracted by lanthanum chloride. Bovine nasal cartilage was extracted with 0.5 M LaCl3 and the extract then diluted with nine volumes of water. The resulting precipitated (PLaCl3) contained the proteoglycan subunits, together with minor protein components, but was essentially free from hyaluronic acid. The properties of PLaCl3 were investigated by chemical analysis, electrophoresis, viscometry and analytical ultracentrifugation, and the results compared with those for proteoglycan obtained by caesium chloride density gradient centrifugation of 2 M CaCl2 cartilage extracts. Proteoglycan subunits (A1D1) prepared from PLaCl3 showed identical properties to those obtained from other high ionic strength cartilage extracts."}
{"id": "PMID:25091", "title": "The involvement of oxygen radicals during the autoxidation of adrenalin.", "content": "1. In unbuffered alkaline solutions, autoxidizing adrenalin generates superoxide anions: both the scavenging by adrenalin itself, leading to adrenochrome, and the formation of nitrite from hydroxylamine are inhibited by superoxide dismutase. No hydroxyl radical could be detected. 2. The yield of hydrogen peroxide increases with pH in a way similar to that of adrenochrome and nitrite. The dissociated form of adrenalin (pK = 8.5) is proposed as the source of superoxide anions. 3. Superoxide dismutase delays rather than inhibits the reaction. In addition to the diminished formation of adrenochrome due to the scavenging of superoxide anions and re-reduction of the semiquinone by hydrogen peroxide, respectively, adrenochrome is further removed by hydrogen peroxide, with final products absorbing at 310 nm. 4. The diminished inhibitory effect of superoxide dismutase above pH 10 is due to superoxide-independent reactions. This effect is masked by the alkaline conversion of adrenochrome to indole compounds. 5. It is concluded that monitoring the absorption of adrenochrome in alkaline solutions does not produce reliable evidence for superoxide anions.", "contents": "The involvement of oxygen radicals during the autoxidation of adrenalin. 1. In unbuffered alkaline solutions, autoxidizing adrenalin generates superoxide anions: both the scavenging by adrenalin itself, leading to adrenochrome, and the formation of nitrite from hydroxylamine are inhibited by superoxide dismutase. No hydroxyl radical could be detected. 2. The yield of hydrogen peroxide increases with pH in a way similar to that of adrenochrome and nitrite. The dissociated form of adrenalin (pK = 8.5) is proposed as the source of superoxide anions. 3. Superoxide dismutase delays rather than inhibits the reaction. In addition to the diminished formation of adrenochrome due to the scavenging of superoxide anions and re-reduction of the semiquinone by hydrogen peroxide, respectively, adrenochrome is further removed by hydrogen peroxide, with final products absorbing at 310 nm. 4. The diminished inhibitory effect of superoxide dismutase above pH 10 is due to superoxide-independent reactions. This effect is masked by the alkaline conversion of adrenochrome to indole compounds. 5. It is concluded that monitoring the absorption of adrenochrome in alkaline solutions does not produce reliable evidence for superoxide anions."}
{"id": "PMID:25092", "title": "A protease-like permeability factor in the guinea pig skin. 1. Partial purification and characterization.", "content": "A permeability factor was extracted in a latent form from guinea pig skin and separated by ammonium sulfate fractionation into the pseudoglobulin fraction (30--50% saturation). The activation of the latent form of the permeability factor seemed to be caused in the desalting step by gel filtration with Sephadex G-50. The factor was partially purified by streptomycin treatment and column chromatography using hydroxyapatite, diethylaminoethyl cellulose and Sephadex G-75, in this order. Gel filtration showed that its molecular weight was approx. 35000. Its permeability activity was heat stable at 61 degrees C for 60 min at neutral pH, resistant at pH 5--10 and at ionic strengths from deionized water to 1 M NaCl at 4 degrees C. Its activity was transient and suppressed by guinea pig serum, but insensitive to an anti-histamic agent (triprolidine). Furthermore, its permeability activity was inhibited by diisopropylfluorophosphate, soybean trypsin inhibitor and leupeptin, and completely adsorbed by soybean trypsin inhibitor affinity column. These findings suggested that the permeability factor was a serine-type protease.", "contents": "A protease-like permeability factor in the guinea pig skin. 1. Partial purification and characterization. A permeability factor was extracted in a latent form from guinea pig skin and separated by ammonium sulfate fractionation into the pseudoglobulin fraction (30--50% saturation). The activation of the latent form of the permeability factor seemed to be caused in the desalting step by gel filtration with Sephadex G-50. The factor was partially purified by streptomycin treatment and column chromatography using hydroxyapatite, diethylaminoethyl cellulose and Sephadex G-75, in this order. Gel filtration showed that its molecular weight was approx. 35000. Its permeability activity was heat stable at 61 degrees C for 60 min at neutral pH, resistant at pH 5--10 and at ionic strengths from deionized water to 1 M NaCl at 4 degrees C. Its activity was transient and suppressed by guinea pig serum, but insensitive to an anti-histamic agent (triprolidine). Furthermore, its permeability activity was inhibited by diisopropylfluorophosphate, soybean trypsin inhibitor and leupeptin, and completely adsorbed by soybean trypsin inhibitor affinity column. These findings suggested that the permeability factor was a serine-type protease."}
{"id": "PMID:25094", "title": "The mobility of methylmercury in biological systems.", "content": "Toxicology studies indicate that methylmercury in humans and other species is bonded to sulfhydryl ligands and that the methylmercury in such complexes is labile even though their thermodynamic stability is large. It is shown in this paper that bimolecular nucleophilic displacement of complexed ligand by sulfhydryl-deprotonated ligand is the major pathway for ligand exchange at physiological pH, while at the pH of the stomach the proton-assisted dissociation of the complex is the predominant means by which exchange occurs. The dynamic and equilibrium aspects of the distribution of methylmercury between chloride and sulfhydryl ligands under the solution conditions of the stomach are also considered with respect to a possible role for lipid-soluble CH3HgCl in the absorption of methylmercury from the stomach.", "contents": "The mobility of methylmercury in biological systems. Toxicology studies indicate that methylmercury in humans and other species is bonded to sulfhydryl ligands and that the methylmercury in such complexes is labile even though their thermodynamic stability is large. It is shown in this paper that bimolecular nucleophilic displacement of complexed ligand by sulfhydryl-deprotonated ligand is the major pathway for ligand exchange at physiological pH, while at the pH of the stomach the proton-assisted dissociation of the complex is the predominant means by which exchange occurs. The dynamic and equilibrium aspects of the distribution of methylmercury between chloride and sulfhydryl ligands under the solution conditions of the stomach are also considered with respect to a possible role for lipid-soluble CH3HgCl in the absorption of methylmercury from the stomach."}
{"id": "PMID:25095", "title": "A light-scattering study of the effect of calcium chloride on the molecular weight of Busycon hemocyanin.", "content": "Solutions of Busycon canaliculatum have been studied by light scattering. In 0.05 M Trizma buffer +0.1 M NaCl at pH 7.0 at 14 degrees, the weight-average molecular weight is 8.9 X 10(6). In the presence of added CaCl2 (0.02 M), the molecular weight of the protein increases to 10.7 X 10(6), and the second virial coefficient is reduced. At pH 9.95, the molecular weights with and without 0.02 M CaCl2, are 3.7 X 10(6) and 1.3 X 10(6), respectively; and the effect of Ca++ in reducing the second virial coefficient is much greater than at pH 7.0. These results can be understood on the basis that at pH 7.0, ca++ increases the association of hemocyanin, by binding and intermolecular linkage through the carboxyl groups of protein side chains. At pH 9.95, amino groups are deprotonated and therefore also become available for Ca++ binding. The relative effect of Ca++ in enhancing the association of hemocyanin therefore becomes greater at the higher pH.", "contents": "A light-scattering study of the effect of calcium chloride on the molecular weight of Busycon hemocyanin. Solutions of Busycon canaliculatum have been studied by light scattering. In 0.05 M Trizma buffer +0.1 M NaCl at pH 7.0 at 14 degrees, the weight-average molecular weight is 8.9 X 10(6). In the presence of added CaCl2 (0.02 M), the molecular weight of the protein increases to 10.7 X 10(6), and the second virial coefficient is reduced. At pH 9.95, the molecular weights with and without 0.02 M CaCl2, are 3.7 X 10(6) and 1.3 X 10(6), respectively; and the effect of Ca++ in reducing the second virial coefficient is much greater than at pH 7.0. These results can be understood on the basis that at pH 7.0, ca++ increases the association of hemocyanin, by binding and intermolecular linkage through the carboxyl groups of protein side chains. At pH 9.95, amino groups are deprotonated and therefore also become available for Ca++ binding. The relative effect of Ca++ in enhancing the association of hemocyanin therefore becomes greater at the higher pH."}
{"id": "PMID:25096", "title": "Effects of ammonium and bicarbonate-CO2 on intracellular chloride levels in Aplysia neurons.", "content": "The level of intracellular free chloride in Aplysia giant neurons can be made to decline by pretreatment with 50 mM NH4+ solution followed by washing with 10 mM HCO3-/0.4% CO2-containing fluids. This effect can be completely blocked by the anion flux inhibitor, 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (SITS). The net change of free chloride in the cell cannot be explained by changes in the electrochemical gradient of chloride. These results support the hypothesis that at least one mechanism for intracellular pH regulation involves a Cl-/HCO-3 exchange process.", "contents": "Effects of ammonium and bicarbonate-CO2 on intracellular chloride levels in Aplysia neurons. The level of intracellular free chloride in Aplysia giant neurons can be made to decline by pretreatment with 50 mM NH4+ solution followed by washing with 10 mM HCO3-/0.4% CO2-containing fluids. This effect can be completely blocked by the anion flux inhibitor, 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (SITS). The net change of free chloride in the cell cannot be explained by changes in the electrochemical gradient of chloride. These results support the hypothesis that at least one mechanism for intracellular pH regulation involves a Cl-/HCO-3 exchange process."}
{"id": "PMID:25100", "title": "Effects of a new selective beta1-adrenoceptor agonist on amylase secretion from the rat parotid gland.", "content": "The effects of a new selective beta1-adrenoceptor agonist, (--)-1-(4-hydroxyphenoxy)-3-isopropyl-amino-propanol-2-hydrochloride (H 133/22), on amylase secretion from the rat parotid gland were investigated in an in vitro system. The results were compared to the secretory responses obtained with noradrenaline, adrenaline, methoxyamine and terbutaline. H 133/22 was found to be a potent enzyme secretagogue and appeared even more effective than noradrenaline and adrenaline, particularly at low concentrations. The beta1-adrenoceptor agonist, terbutaline, also stimulated amylase discharge from the parotid gland but was much less potent than H 133/22. Methoxyamine had no effect on enzyme secretion. We suggest that the adrenergic stimulation of amylase secretion from the rat parotid gland is mainly mediated by beta1-receptors.", "contents": "Effects of a new selective beta1-adrenoceptor agonist on amylase secretion from the rat parotid gland. The effects of a new selective beta1-adrenoceptor agonist, (--)-1-(4-hydroxyphenoxy)-3-isopropyl-amino-propanol-2-hydrochloride (H 133/22), on amylase secretion from the rat parotid gland were investigated in an in vitro system. The results were compared to the secretory responses obtained with noradrenaline, adrenaline, methoxyamine and terbutaline. H 133/22 was found to be a potent enzyme secretagogue and appeared even more effective than noradrenaline and adrenaline, particularly at low concentrations. The beta1-adrenoceptor agonist, terbutaline, also stimulated amylase discharge from the parotid gland but was much less potent than H 133/22. Methoxyamine had no effect on enzyme secretion. We suggest that the adrenergic stimulation of amylase secretion from the rat parotid gland is mainly mediated by beta1-receptors."}
{"id": "PMID:25117", "title": "The effect of lysergic and diethylamide (LSD) and 2-bromolysergic acid diethylamide (BOL) on the striatal DOPA accumulation: influence of central 5-hydroxytryptaminergic pathways.", "content": "Selective chronic lesions of the dorsal raphe nucleus or combined lesions of the dorsal and median raphe nuclei did not significantly change the in vivo tyrosine hydroxylation in the striatum as measured by the DOPA accumulation after decarboxylase inhibition. Neither did acute combined lesions of the raphe nuclei, nor did electrical stimulation of the dorsal raphe nucleus have any significant effect. p-Chloroamphetamine (PCA, 20 mg/kg, i.p.) and p-chlorophenylalanine (PCPA, 400 mg/kg, i.p.), known inhibitors of the 5-hydroxytryptamine (5-HT) synthesis, significantly decreased the DOPA accumulation. The increase in DOPA accumulation observed after LSD (0.5 mg/kg, i.p.) or BOL (0.5 mg/kg, i.p.) was seemingly unaffected by pretreatment with PCA or PCPA and also after lesion of the dorsal raphe nucleus. The results suggest that the effect of LSD or BOL on the DOPA accumulation in the striatum is not mediated via a 5-hydroxytryptaminergic control mechanism originating in the dorsal raphe nucleus. A control mediated via the median raphe nucleus cannot be excluded, since LSD did not increase the DOPA accumulation after combined chronic raphe lesions. Such a control would also be in agreement with our previous results suggesting that hte DOPA generation after LSD is controlled by 5-HT receptors.", "contents": "The effect of lysergic and diethylamide (LSD) and 2-bromolysergic acid diethylamide (BOL) on the striatal DOPA accumulation: influence of central 5-hydroxytryptaminergic pathways. Selective chronic lesions of the dorsal raphe nucleus or combined lesions of the dorsal and median raphe nuclei did not significantly change the in vivo tyrosine hydroxylation in the striatum as measured by the DOPA accumulation after decarboxylase inhibition. Neither did acute combined lesions of the raphe nuclei, nor did electrical stimulation of the dorsal raphe nucleus have any significant effect. p-Chloroamphetamine (PCA, 20 mg/kg, i.p.) and p-chlorophenylalanine (PCPA, 400 mg/kg, i.p.), known inhibitors of the 5-hydroxytryptamine (5-HT) synthesis, significantly decreased the DOPA accumulation. The increase in DOPA accumulation observed after LSD (0.5 mg/kg, i.p.) or BOL (0.5 mg/kg, i.p.) was seemingly unaffected by pretreatment with PCA or PCPA and also after lesion of the dorsal raphe nucleus. The results suggest that the effect of LSD or BOL on the DOPA accumulation in the striatum is not mediated via a 5-hydroxytryptaminergic control mechanism originating in the dorsal raphe nucleus. A control mediated via the median raphe nucleus cannot be excluded, since LSD did not increase the DOPA accumulation after combined chronic raphe lesions. Such a control would also be in agreement with our previous results suggesting that hte DOPA generation after LSD is controlled by 5-HT receptors."}
{"id": "PMID:25118", "title": "Monoamines, estrogen and female sexual behavior in the golden hamster.", "content": "In the golden hamster drugs which inhibit monoaminergic function (including p-chlorophenylalanine (PCPA), methysergide and a-methyl-p-tyrosine (a-MPT) facilitated lordosis in ovariectomized female hamsters as a function of the duration of estradiol benzoate (EB) priming. a-MPT (200 mg/kg), methysergide (6 mg/animal) or PCPA (150 or 360 mg/kg) potentiated lordosis if 6 days of EB priming preceded drug treatment. However, if female hamsters were primed with EB for only 2 days, a-MPT and methysergide were ineffective. PCPA (360 mg/kg) was less effective after 2 days of EB than after 6 days of EB priming. alpha-MPT produced a three-fold elevation in progesterone levels in ovariectomized females but methysergide and PCPA did not influence serum progesterone. PCPA (360 mg/kg) facilitated lordosis in adrenalectomized, ovariectomized females, eliminating the possibility that adrenal progesterone is essential for the behavioral effects of the drug. Luteinizing hormone-releasing hormone levels in the preoptic/anterior hypothalamic area and the medial basal hypothalamus were also not significantly altered at 1 h after PCPA injection. Pimozide (1.5 mg/kg) and pimozide (1.5 mg/kg) and amphetamine (2.5 mg/kg) did not potentiate lordosis in ovariectomized hamsters after either 2 or 6 days of EB priming. Pargyline, a monoamine oxidase inhibitor, inhibited female sexual behavior in females in estrogen alone-induced estrus. Lordosis in the female rat is more readily elicited both by drugs and estrogen. It is proposed with regard to female sexual behavior that species differences in estrogen sensitivity may underlie apparent differences in drug sensitivity.", "contents": "Monoamines, estrogen and female sexual behavior in the golden hamster. In the golden hamster drugs which inhibit monoaminergic function (including p-chlorophenylalanine (PCPA), methysergide and a-methyl-p-tyrosine (a-MPT) facilitated lordosis in ovariectomized female hamsters as a function of the duration of estradiol benzoate (EB) priming. a-MPT (200 mg/kg), methysergide (6 mg/animal) or PCPA (150 or 360 mg/kg) potentiated lordosis if 6 days of EB priming preceded drug treatment. However, if female hamsters were primed with EB for only 2 days, a-MPT and methysergide were ineffective. PCPA (360 mg/kg) was less effective after 2 days of EB than after 6 days of EB priming. alpha-MPT produced a three-fold elevation in progesterone levels in ovariectomized females but methysergide and PCPA did not influence serum progesterone. PCPA (360 mg/kg) facilitated lordosis in adrenalectomized, ovariectomized females, eliminating the possibility that adrenal progesterone is essential for the behavioral effects of the drug. Luteinizing hormone-releasing hormone levels in the preoptic/anterior hypothalamic area and the medial basal hypothalamus were also not significantly altered at 1 h after PCPA injection. Pimozide (1.5 mg/kg) and pimozide (1.5 mg/kg) and amphetamine (2.5 mg/kg) did not potentiate lordosis in ovariectomized hamsters after either 2 or 6 days of EB priming. Pargyline, a monoamine oxidase inhibitor, inhibited female sexual behavior in females in estrogen alone-induced estrus. Lordosis in the female rat is more readily elicited both by drugs and estrogen. It is proposed with regard to female sexual behavior that species differences in estrogen sensitivity may underlie apparent differences in drug sensitivity."}
{"id": "PMID:25121", "title": "Synaptic connexions and related postsynaptic pharmacology studied in the cerebral ganglion of Aplysia.", "content": "Interneuronal connexions have been studied within the cerebral ganglion of Aplysia californica. Excitatory monosynaptic connexions between two groups of cells located on the dorsal surface of the ganglion near the cerebropleural connectives were analyzed in detail. The monosynapticity of these connexions was established not only by the strict one-to-one correlation between presynaptic action potential and excitatory postsynaptic response (EPSP) and the constant latency for any given cell pair, but also by the following criteria: (a) gradual change in the EPSP following tetraethylammonium injection into the presynaptic neurone, (b) sustained EPSP in the presence of a high external calcium ion concentration, (c) sensitivity of the EPSP amplitude to presynaptic polarization. Iontophoretic application of acetylcholine, 5-hydroxytryptamine and glutamate on the postsynaptic cells elicited excitatory responses in many cases. Inhibitory responses were obtained by local iontophoresis of dopamine, gamma-aminobutyric acid and occasionally also by acetylcholine. The only agent found to block the EPSP was bufotenine, which also readily blocked the 5-hydroxytryptamine response. Bufotenine was completely ineffective on the acetylcholine or glutamate excitatory responses. Of the various cholinolytics tested, none had an effect on the EPSP. Our data all point to 5-hydroxytryptamine as a transmitter in the studied synaptic connexions. However, it must be emphasized that in the absence of biochemical and histological evidence the role of the 5-hydroxytryptamine cannot be regarded as conclusive.", "contents": "Synaptic connexions and related postsynaptic pharmacology studied in the cerebral ganglion of Aplysia. Interneuronal connexions have been studied within the cerebral ganglion of Aplysia californica. Excitatory monosynaptic connexions between two groups of cells located on the dorsal surface of the ganglion near the cerebropleural connectives were analyzed in detail. The monosynapticity of these connexions was established not only by the strict one-to-one correlation between presynaptic action potential and excitatory postsynaptic response (EPSP) and the constant latency for any given cell pair, but also by the following criteria: (a) gradual change in the EPSP following tetraethylammonium injection into the presynaptic neurone, (b) sustained EPSP in the presence of a high external calcium ion concentration, (c) sensitivity of the EPSP amplitude to presynaptic polarization. Iontophoretic application of acetylcholine, 5-hydroxytryptamine and glutamate on the postsynaptic cells elicited excitatory responses in many cases. Inhibitory responses were obtained by local iontophoresis of dopamine, gamma-aminobutyric acid and occasionally also by acetylcholine. The only agent found to block the EPSP was bufotenine, which also readily blocked the 5-hydroxytryptamine response. Bufotenine was completely ineffective on the acetylcholine or glutamate excitatory responses. Of the various cholinolytics tested, none had an effect on the EPSP. Our data all point to 5-hydroxytryptamine as a transmitter in the studied synaptic connexions. However, it must be emphasized that in the absence of biochemical and histological evidence the role of the 5-hydroxytryptamine cannot be regarded as conclusive."}
{"id": "PMID:25128", "title": "Effects of pH and flow rate on the release of 'bound' red cells from the splenic pulp.", "content": "On perfusion of isolated, denervated spleens with Ringer solution, immature and abnormal red cells are released into the venous outflow much more slowly than normal mature cells, being delayed through adherence to fine structures of the red pulp (Am. J. Physiol. 231, 1665-1671 (1976)). Evidence suggested that the rate at which such cells are released from the 'bound' state might depend on local pH and fluid shear rate within the pulp. Therefore, the rate of washout for this slow component of red cells, from cat spleens, was measured as a function of pH and flow rate of the perfusate. The volume of solution (V 1/2) for 50% washout of 'bound' cells decreased as pH was lowered from 7.8 to 6.6, especially (from 97 to 18 ml/g) between 7.4 and 6.6. The percentage total red cell outflow thus represented rose from 0.06 to 0.5 as pH fell from 7.8 to 6.6. At a high perfusion rate (14-16 ml/min) the V 1/2 value was only one-half that prevailing at a lower rate (4-6 ml/min), and the percentage flow of 'bound' red cells was more than three times greater. Both acidic pH and augmented blood flow thus assist release of adherent red cells from the splenic pulp.", "contents": "Effects of pH and flow rate on the release of 'bound' red cells from the splenic pulp. On perfusion of isolated, denervated spleens with Ringer solution, immature and abnormal red cells are released into the venous outflow much more slowly than normal mature cells, being delayed through adherence to fine structures of the red pulp (Am. J. Physiol. 231, 1665-1671 (1976)). Evidence suggested that the rate at which such cells are released from the 'bound' state might depend on local pH and fluid shear rate within the pulp. Therefore, the rate of washout for this slow component of red cells, from cat spleens, was measured as a function of pH and flow rate of the perfusate. The volume of solution (V 1/2) for 50% washout of 'bound' cells decreased as pH was lowered from 7.8 to 6.6, especially (from 97 to 18 ml/g) between 7.4 and 6.6. The percentage total red cell outflow thus represented rose from 0.06 to 0.5 as pH fell from 7.8 to 6.6. At a high perfusion rate (14-16 ml/min) the V 1/2 value was only one-half that prevailing at a lower rate (4-6 ml/min), and the percentage flow of 'bound' red cells was more than three times greater. Both acidic pH and augmented blood flow thus assist release of adherent red cells from the splenic pulp."}
{"id": "PMID:25129", "title": "An alkaline phosphatase mutant of Pseudomonas aeruginosa. 1. Effects of regulatory, structural, and environmental shifts on enzyme function.", "content": "An alkaline phosphatase mutant of Pseudomonas aeruginosa exhibiting both regulatory and catalytic changes was isolated. Under repression conditions (i.e. high inorganic phosphate (Pi)) the mutant culture produced an alkaline phosphatase (APase) displaying significant activity against both beta-glycerol phosphate (betaGP) and p-nitrophenyl phosphate (pNPP), while the wild type displayed no activity directed towards these substrates under the same conditions. In vivo, the mutant enzyme's ratio of specific activities was 45:1 in favour of betaGP versus pNPP, whereas this ratio was reversed to 1:9 betaGP versus pNPP for the same enzyme isolated from mutant cells. In addition, the kinetic parameters and stability requirements for the mutant-derived enzyme was altered in comparison with those of the wild type. A study of lipopolysaccharide (LPS) preparations from both the mutant and wild type indicated the mutant to be deficient in the core region of its LPS. The authors propose that the modifications in the catalytic activity of the mutant enzyme, demonstrated in vivo, are due to a change in the enzyme's microenvironment.", "contents": "An alkaline phosphatase mutant of Pseudomonas aeruginosa. 1. Effects of regulatory, structural, and environmental shifts on enzyme function. An alkaline phosphatase mutant of Pseudomonas aeruginosa exhibiting both regulatory and catalytic changes was isolated. Under repression conditions (i.e. high inorganic phosphate (Pi)) the mutant culture produced an alkaline phosphatase (APase) displaying significant activity against both beta-glycerol phosphate (betaGP) and p-nitrophenyl phosphate (pNPP), while the wild type displayed no activity directed towards these substrates under the same conditions. In vivo, the mutant enzyme's ratio of specific activities was 45:1 in favour of betaGP versus pNPP, whereas this ratio was reversed to 1:9 betaGP versus pNPP for the same enzyme isolated from mutant cells. In addition, the kinetic parameters and stability requirements for the mutant-derived enzyme was altered in comparison with those of the wild type. A study of lipopolysaccharide (LPS) preparations from both the mutant and wild type indicated the mutant to be deficient in the core region of its LPS. The authors propose that the modifications in the catalytic activity of the mutant enzyme, demonstrated in vivo, are due to a change in the enzyme's microenvironment."}
{"id": "PMID:25130", "title": "Proteolytic activity of Trichoderma viride in mixed culture with Sclerotium rolfsii in soil.", "content": "Cultures of Sclerotium rolfsii and Trichoderma viride together in autoclaved soil were assayed at intervals during 8 days of incubation for proteolytic activity (PA) of T. viride. Significant proteolytic activity was detected only in soil containing T. viride (i.e., T. viride alone or S. rolfsii + T. viride); greatest activity occurred between 3 and 4 days after infestation and declined rapidly thereafter. Maximal PA in the mixed-culture soil was accompanied by an increase in soil pH. optimal pH values for PA was 5.5-6.5 with a maximum at 6.0.", "contents": "Proteolytic activity of Trichoderma viride in mixed culture with Sclerotium rolfsii in soil. Cultures of Sclerotium rolfsii and Trichoderma viride together in autoclaved soil were assayed at intervals during 8 days of incubation for proteolytic activity (PA) of T. viride. Significant proteolytic activity was detected only in soil containing T. viride (i.e., T. viride alone or S. rolfsii + T. viride); greatest activity occurred between 3 and 4 days after infestation and declined rapidly thereafter. Maximal PA in the mixed-culture soil was accompanied by an increase in soil pH. optimal pH values for PA was 5.5-6.5 with a maximum at 6.0."}
{"id": "PMID:25135", "title": "Proliferation and viability in cellular spheroids of human origin.", "content": "The capacity of cells to form growing tumor-like colonies in culture was tested by a new and unlaborious suspension technique. Six of nine tested cell lines formed spheroids, five of which started to grow. The growing spheroids reached a maximal size determined by balanced cell gain in a proliferative, superficial layer and cell death, particularly at larger depth. Sections of spheroids of different origin showed large variations in the thickness of the viable cell layers and in the shape of the proliferative gradients. The data, taken together with earlier published information, indicate that a difference between rodent and human cells generally exists, the former showing thinner viable and proliferative layers.", "contents": "Proliferation and viability in cellular spheroids of human origin. The capacity of cells to form growing tumor-like colonies in culture was tested by a new and unlaborious suspension technique. Six of nine tested cell lines formed spheroids, five of which started to grow. The growing spheroids reached a maximal size determined by balanced cell gain in a proliferative, superficial layer and cell death, particularly at larger depth. Sections of spheroids of different origin showed large variations in the thickness of the viable cell layers and in the shape of the proliferative gradients. The data, taken together with earlier published information, indicate that a difference between rodent and human cells generally exists, the former showing thinner viable and proliferative layers."}
{"id": "PMID:25144", "title": "Enzymatic determination of blood ethanol, with amperometric measurement of rate of oxygen depletion.", "content": "A rapid electrochemical measurement of blood ethanol is proposed. Alcohol is oxidized by NAD+ in the presence of alcohol dehydrogenase; and the NADH produced is aerobically oxidized by horseradish peroxidase. The rate of depletion of buffer-carried oxygen, which is directly proportional to the alcohol concentration in the sample, is amperometrically monitored with a membrane oxygen-sensing electrode. Only a 5-microliter sample of whole blood is required, with no deproteinization, incubation, extraction, or dilution. Results, obtained in less than 1 min, correlate well with those obtained by gas-chromatographic and spectrophotometric methods.", "contents": "Enzymatic determination of blood ethanol, with amperometric measurement of rate of oxygen depletion. A rapid electrochemical measurement of blood ethanol is proposed. Alcohol is oxidized by NAD+ in the presence of alcohol dehydrogenase; and the NADH produced is aerobically oxidized by horseradish peroxidase. The rate of depletion of buffer-carried oxygen, which is directly proportional to the alcohol concentration in the sample, is amperometrically monitored with a membrane oxygen-sensing electrode. Only a 5-microliter sample of whole blood is required, with no deproteinization, incubation, extraction, or dilution. Results, obtained in less than 1 min, correlate well with those obtained by gas-chromatographic and spectrophotometric methods."}
{"id": "PMID:25145", "title": "Simultaneous liquid-chromatographic determination of 12 common sedatives and hypnotics in serum.", "content": "We present a method for simultaneously determining 12 hypnotics and sedatives (primidone, methyprylon, phenobarbital, butabarbital, butalbital, ethchlorvynol, pentobarbital, amobarbital, phenytoin, glutethimide, secobarbital and methaqualone) in 200 microliter of serum. Serum proteins are precipitated with an acetonitrile solution containing 5-(4-methylphenyl)-5-phenylhydantoin, the internal standard. The drugs are eluted from a reversed-phase column with a mobile phase consisting of an acetonitrile/phosphate buffer, at a flow rate of 3.0 ml/min. The eluted drugs are detected by their absorption at 195 nm; their quantities are estimated from their peak heights. Each analysis requires no longer than 30 min at the optimum column temperature of 50 degrees C. The lower limit of detection for all of these drugs is less than 10 ng/sample for drug standard. A sensitivity of 1.0 mg/liter of serum is attained routinely for each of the drugs. Analytical recoveries for the 12 drugs varied from 94 to 112%, with good day-to-day precision (CV between 3.8 and 10.4%). Of more than 35 drugs tested for possible interference, only ethotoin interferes with the analysis of phenobarbital.", "contents": "Simultaneous liquid-chromatographic determination of 12 common sedatives and hypnotics in serum. We present a method for simultaneously determining 12 hypnotics and sedatives (primidone, methyprylon, phenobarbital, butabarbital, butalbital, ethchlorvynol, pentobarbital, amobarbital, phenytoin, glutethimide, secobarbital and methaqualone) in 200 microliter of serum. Serum proteins are precipitated with an acetonitrile solution containing 5-(4-methylphenyl)-5-phenylhydantoin, the internal standard. The drugs are eluted from a reversed-phase column with a mobile phase consisting of an acetonitrile/phosphate buffer, at a flow rate of 3.0 ml/min. The eluted drugs are detected by their absorption at 195 nm; their quantities are estimated from their peak heights. Each analysis requires no longer than 30 min at the optimum column temperature of 50 degrees C. The lower limit of detection for all of these drugs is less than 10 ng/sample for drug standard. A sensitivity of 1.0 mg/liter of serum is attained routinely for each of the drugs. Analytical recoveries for the 12 drugs varied from 94 to 112%, with good day-to-day precision (CV between 3.8 and 10.4%). Of more than 35 drugs tested for possible interference, only ethotoin interferes with the analysis of phenobarbital."}
{"id": "PMID:25149", "title": "The use of gamma-glutamyl-p-aminobenzoic acid as the substrate for determination of gamma-glutamyltranspeptidase activity in blood serum.", "content": "By the phthaloyl method less toxic and readily soluble gamma-L-glutamyl-p-aminobenzoic acid was synthesized. This substance was used as a substrate for gamma-glutamyltranspeptidase activity assay in blood serum and urine. Close correlation was shown between the results obtained with the new method and with the old one which used gamma-L-glutamyl-p-nitroanilide.", "contents": "The use of gamma-glutamyl-p-aminobenzoic acid as the substrate for determination of gamma-glutamyltranspeptidase activity in blood serum. By the phthaloyl method less toxic and readily soluble gamma-L-glutamyl-p-aminobenzoic acid was synthesized. This substance was used as a substrate for gamma-glutamyltranspeptidase activity assay in blood serum and urine. Close correlation was shown between the results obtained with the new method and with the old one which used gamma-L-glutamyl-p-nitroanilide."}
{"id": "PMID:25150", "title": "The effect of urinary pH and flow rate on monoamine output.", "content": "Three-hour urinary output values of dopamine, noradrenaline, adrenaline, 2-phenylethylamine and p-tyramine were measured in normal volunteers who had been induced, by pretreatment with ammonium chloride or sodium bicarbonate, to excrete maximally acid or alkaline urine. There were significant effects on the excretion of dopamine, adrenaline and 2-phenylethylamine, inversely proportional to urinary pH value. Adrenaline output increased with increasing urinary flow rate. There was a significant correlation between urinary concentrations of 2-phenylethylamine and p-tyramine. These findings may have important clinical implications.", "contents": "The effect of urinary pH and flow rate on monoamine output. Three-hour urinary output values of dopamine, noradrenaline, adrenaline, 2-phenylethylamine and p-tyramine were measured in normal volunteers who had been induced, by pretreatment with ammonium chloride or sodium bicarbonate, to excrete maximally acid or alkaline urine. There were significant effects on the excretion of dopamine, adrenaline and 2-phenylethylamine, inversely proportional to urinary pH value. Adrenaline output increased with increasing urinary flow rate. There was a significant correlation between urinary concentrations of 2-phenylethylamine and p-tyramine. These findings may have important clinical implications."}
{"id": "PMID:25151", "title": "Acid esterase activity in cultured skin fibroblasts and amniotic fluid cells using 4-methylumbelliferyl palmitate.", "content": "The properties and levels of acid esterase in cultured skin fibroblasts and amniotic fluid cells were investigated using 4-methylumbelliferyl palmitate as substrate. Determinations of acid esterase activity could be made using as little as 1 microgram cell protein. Cardiolipin increased the activity 2--3 fold at the pH optimum 4.0. The apparent KM for both cell types studied was 196 micrometer without and 96 micrometer with cardiolipin. Acid esterase activity was inhibited by cyanide and thiomersal, but not by iodoacetate and N-ethylmaleimide. However activation by cardiolipin was prevented by iodoacetate, N-ethylmaleimide and also sodium chloride. Skin fibroblasts and primary amniotic fluid cells had similar levels with or without cardiolipin. A cyclic activity was found with subculture but no consistent pattern with passage. The acid esterase deficiency in Wolman's and cholesterol ester storage diseases was demonstrated with this substrate.", "contents": "Acid esterase activity in cultured skin fibroblasts and amniotic fluid cells using 4-methylumbelliferyl palmitate. The properties and levels of acid esterase in cultured skin fibroblasts and amniotic fluid cells were investigated using 4-methylumbelliferyl palmitate as substrate. Determinations of acid esterase activity could be made using as little as 1 microgram cell protein. Cardiolipin increased the activity 2--3 fold at the pH optimum 4.0. The apparent KM for both cell types studied was 196 micrometer without and 96 micrometer with cardiolipin. Acid esterase activity was inhibited by cyanide and thiomersal, but not by iodoacetate and N-ethylmaleimide. However activation by cardiolipin was prevented by iodoacetate, N-ethylmaleimide and also sodium chloride. Skin fibroblasts and primary amniotic fluid cells had similar levels with or without cardiolipin. A cyclic activity was found with subculture but no consistent pattern with passage. The acid esterase deficiency in Wolman's and cholesterol ester storage diseases was demonstrated with this substrate."}
{"id": "PMID:25152", "title": "Cardiac and bronchial beta-adrenoceptor antagonistic potencies of atenolol, metoprolol, acebutolol, practolol, propranolol and pindolol in the anaesthetized dog.", "content": "1. The beta-adrenoceptor antagonists atenolol, metoprolol, acebutolol, practolol, propranolol and pindolol have been tested for their ability to reduce isoprenaline-induced bronchodilation and tachycardia in the anaesthetized dog. 2. Atenolol, metoprolol, acebutolol and practolol all possessed a similar degree of cardioselectivity in this animal model.", "contents": "Cardiac and bronchial beta-adrenoceptor antagonistic potencies of atenolol, metoprolol, acebutolol, practolol, propranolol and pindolol in the anaesthetized dog. 1. The beta-adrenoceptor antagonists atenolol, metoprolol, acebutolol, practolol, propranolol and pindolol have been tested for their ability to reduce isoprenaline-induced bronchodilation and tachycardia in the anaesthetized dog. 2. Atenolol, metoprolol, acebutolol and practolol all possessed a similar degree of cardioselectivity in this animal model."}
{"id": "PMID:25153", "title": "The influence of serotonin on the mitotic rate in the colonic crypt epithelium and in colonic adenocarcinoma in rats.", "content": "1. The mitotic rate in the crypts of Lieberk\u00fchn of the descending colon and in dimethylhydrazine-induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique. 2. Intraperitoneal injection of a small dose (10 microgram/kg) of serotonin resulted in an increase in the tumour cell mitotic rate. 3. Blockade of serotonin receptors by 2-bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL-6-fluorotryptophan both result in a decrease in the tumour cell mitotic rate. 4. Treatment with serotonin, 2-bromolysergic acid diethylamide and DL-6-fluorotryptophan were all without effect on the colonic crypt cell mitotic rate.", "contents": "The influence of serotonin on the mitotic rate in the colonic crypt epithelium and in colonic adenocarcinoma in rats. 1. The mitotic rate in the crypts of Lieberk\u00fchn of the descending colon and in dimethylhydrazine-induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique. 2. Intraperitoneal injection of a small dose (10 microgram/kg) of serotonin resulted in an increase in the tumour cell mitotic rate. 3. Blockade of serotonin receptors by 2-bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL-6-fluorotryptophan both result in a decrease in the tumour cell mitotic rate. 4. Treatment with serotonin, 2-bromolysergic acid diethylamide and DL-6-fluorotryptophan were all without effect on the colonic crypt cell mitotic rate."}
{"id": "PMID:25157", "title": "Kinetics, salivary excretion of amphetamine isomers, and effect of urinary pH.", "content": "Amphetamine was administered to healthy subjects as the racemic mixture and as (+)- and (-)-isomers under conditions of urine acidification and alkalinization. Plasma and saliva concentration of each isomer was measured and the kinetics of the individual isomers were determined. (+)-amphetamine was eliminated more rapidly than the (-)-isomer. The difference in half-life between isomers was maximal under basic urinary pH conditions. Saliva amphetamine levels were higher than plasma levels and in the postabsorptive phase were predictably proportional to plasma drug levels.", "contents": "Kinetics, salivary excretion of amphetamine isomers, and effect of urinary pH. Amphetamine was administered to healthy subjects as the racemic mixture and as (+)- and (-)-isomers under conditions of urine acidification and alkalinization. Plasma and saliva concentration of each isomer was measured and the kinetics of the individual isomers were determined. (+)-amphetamine was eliminated more rapidly than the (-)-isomer. The difference in half-life between isomers was maximal under basic urinary pH conditions. Saliva amphetamine levels were higher than plasma levels and in the postabsorptive phase were predictably proportional to plasma drug levels."}
{"id": "PMID:25154", "title": "Plasma level monitoring of antipsychotic drugs.", "content": "Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage. Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients. Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest.", "contents": "Plasma level monitoring of antipsychotic drugs. Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage. Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients. Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest."}
{"id": "PMID:25156", "title": "Diseases and drug protein binding.", "content": "In a number of pathological states a decrease in the plasma protein binding of drugs is observed. This may be due to many factors related either to the protein, or the ligand (drug), or to the binding conditions. The most important of these disease states quantitatively are probably hypoalbuminaemia, conditions resulting in modification of the albumin compartment volume and the presence on albumin binding sites of pathological inhibitors of drug binding. A decrease in the extent of drug plasma protein binding does not necessarily lead to enhanced drug effects and therefore raises two important therapeutic questions. Firstly, does reduced protein binding have a clinically significant influence on the pharmacological effects of the drug? Secondly, if it does, is it preferable to modify the dosage regimen of the drug or to correct the plasma protein concentration prior to the administration of the drug? At present, only tentative answers can be given.", "contents": "Diseases and drug protein binding. In a number of pathological states a decrease in the plasma protein binding of drugs is observed. This may be due to many factors related either to the protein, or the ligand (drug), or to the binding conditions. The most important of these disease states quantitatively are probably hypoalbuminaemia, conditions resulting in modification of the albumin compartment volume and the presence on albumin binding sites of pathological inhibitors of drug binding. A decrease in the extent of drug plasma protein binding does not necessarily lead to enhanced drug effects and therefore raises two important therapeutic questions. Firstly, does reduced protein binding have a clinically significant influence on the pharmacological effects of the drug? Secondly, if it does, is it preferable to modify the dosage regimen of the drug or to correct the plasma protein concentration prior to the administration of the drug? At present, only tentative answers can be given."}
{"id": "PMID:25163", "title": "Acid-base balance in small premature infants (less than 1500 grams) with type II RDS.", "content": "Twenty-one small premature infants with clinical features and radiological findings of type II RDS were studied. Correction of blood pH, corresponding with the decrease of blood PaCO2, was usually seen in the first eight hours of age. Clinical inprovement, as judged by the RDS score, was noted only after 12 hours of age. Complete recovery was the rule although signs of respiratory distress in a few infants lasted for 48-72 hours. The calculated AaDO2 and total Qs/Qt weer slightly higher (27.8%) than reported in normal infants and remained unchanged until after 48 hours of age when it decreased to 24.5%.", "contents": "Acid-base balance in small premature infants (less than 1500 grams) with type II RDS. Twenty-one small premature infants with clinical features and radiological findings of type II RDS were studied. Correction of blood pH, corresponding with the decrease of blood PaCO2, was usually seen in the first eight hours of age. Clinical inprovement, as judged by the RDS score, was noted only after 12 hours of age. Complete recovery was the rule although signs of respiratory distress in a few infants lasted for 48-72 hours. The calculated AaDO2 and total Qs/Qt weer slightly higher (27.8%) than reported in normal infants and remained unchanged until after 48 hours of age when it decreased to 24.5%."}
{"id": "PMID:25167", "title": "Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent.", "content": "Loxapine is a dibenzoxazepine, tricyclic compound recommended for the treatment of acute and chronic schizophrenia. In its therapeutic effectiveness and profile and incidence of side-effects, loxapine closely resembles the traditional antipsychotic agents. Although loxapine has tended to be less effective than some standard antipsychotic drugs in a few short-term (3 to 4 weeks) studies, it has been superior to a placebo and about as effective as chlorpromazine, haloperidol, trifluoperazine or thiothixene when evaluated after 4 to 12 weeks. Like the phenothiazine (e.g. chlorpromazine) and butyrophenone (e.g. haloperidol) antipsychotic agents, loxapine causes a high incidence of extrapyramidal reactions. Sedation occurs frequently, especially during early stages of treatment. Other, less common side-effects such as anticholinergic effects (dry mouth, blurred vision, etc.), hypotension, tachycardia and precipitation of epileptic seizures, which occur with the older antipsychotic drugs, have also been reported with loxapine.", "contents": "Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent. Loxapine is a dibenzoxazepine, tricyclic compound recommended for the treatment of acute and chronic schizophrenia. In its therapeutic effectiveness and profile and incidence of side-effects, loxapine closely resembles the traditional antipsychotic agents. Although loxapine has tended to be less effective than some standard antipsychotic drugs in a few short-term (3 to 4 weeks) studies, it has been superior to a placebo and about as effective as chlorpromazine, haloperidol, trifluoperazine or thiothixene when evaluated after 4 to 12 weeks. Like the phenothiazine (e.g. chlorpromazine) and butyrophenone (e.g. haloperidol) antipsychotic agents, loxapine causes a high incidence of extrapyramidal reactions. Sedation occurs frequently, especially during early stages of treatment. Other, less common side-effects such as anticholinergic effects (dry mouth, blurred vision, etc.), hypotension, tachycardia and precipitation of epileptic seizures, which occur with the older antipsychotic drugs, have also been reported with loxapine."}
{"id": "PMID:25170", "title": "[Hypotensive and antihypertensive activity of a newly synthesized derivative of 2-aminotetralin].", "content": "The report describes the hypotensive and antihypertensive activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphtyl)-N'-(3-oxo-3-phenylpropyl) piperazine dihydrochloride (P11). The work is made on normotensive cats and rats as well as on spontaneous and experimental (metacorticoid) hypertension. The studies were carried out under the conditions of acute and chronic experiment as the arteria pressure was recorded by blood and bloodless method. The compound P11 show a manifested hypotensive activity with favourable duration and therapeutic width. Its antihypertensive activity is revealed in rats with spontaneous and metacorticoid hypertension both after single and chronic applciation of the compound. The influence on the blood pressure weakens after reserpinization of the animals. The compound possesses slight ganglion-blocking action and manifested alpha and beta adreno-blocking activity: diminishes noradrenaline, adrenaline and isoprenaline responses on the arterial pressure and heart activity in anesthetised cats and rats, shifts to the right the cumulative dose-response curve of noradrenaline on vas deferens of a rat, ect. The hypotensive and antihypertensive effect of the compound P11 is discussed on the basis of its alpha and beta adrenoblocking action and its specific sedative effect.", "contents": "[Hypotensive and antihypertensive activity of a newly synthesized derivative of 2-aminotetralin]. The report describes the hypotensive and antihypertensive activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphtyl)-N'-(3-oxo-3-phenylpropyl) piperazine dihydrochloride (P11). The work is made on normotensive cats and rats as well as on spontaneous and experimental (metacorticoid) hypertension. The studies were carried out under the conditions of acute and chronic experiment as the arteria pressure was recorded by blood and bloodless method. The compound P11 show a manifested hypotensive activity with favourable duration and therapeutic width. Its antihypertensive activity is revealed in rats with spontaneous and metacorticoid hypertension both after single and chronic applciation of the compound. The influence on the blood pressure weakens after reserpinization of the animals. The compound possesses slight ganglion-blocking action and manifested alpha and beta adreno-blocking activity: diminishes noradrenaline, adrenaline and isoprenaline responses on the arterial pressure and heart activity in anesthetised cats and rats, shifts to the right the cumulative dose-response curve of noradrenaline on vas deferens of a rat, ect. The hypotensive and antihypertensive effect of the compound P11 is discussed on the basis of its alpha and beta adrenoblocking action and its specific sedative effect."}
{"id": "PMID:25166", "title": "Effects of local delayed hypersensitivity on the small intestine.", "content": "There are many T and B cells in the small intestinal mucosa and local T cell immunity could have a role both in protective immunity and as a cause of disease (i.e. hypersensitivity). This latter aspect has been investigated by using several animal models to assess the effects of local delayed hypersensitivity on the structure and function of the small intestine. Heterotopically transplanted grafts of fetal small intestine in mice (isografts and allografts) have been examined by conventional histology, scanning and transmission electron microscopy, by making direct measurements of villi, crypts, and lymphoid cell infiltrate, and by counting the number of mitoses per crypt. This cell-mediated immune reaction causes lymphocyte infiltration which is most marked in the lamina propria, hyperplasia of the crypts of Lieberk\u00fchn, increased cell loss with villous atrophy and a flat surface, but the individual enterocytes appear fairly normal. Graft-versus-host disease cause exactly the same changes in structure and in cell kinetics as does rejection. However, crypt hyperplasia has been found to precede villous atrophy by several days. Preliminary experiments on local contact hypersensitivity suggest that intraluminal injection of oxazolone in the gut of sensitized mice also produces villous atrophy and crypt hyperplasia. It is postulated that these effects are likely to be produced via lymphokines: by an 'enteropathic' factor which damages the lamina propria and basement membrane, and a factor which is mitogenic for crypt stem cells. In mice infected with Giardia lamblia, crypt hyperplasia and lymphocyte infiltration of the epithelium are present and there is accelerated epithelial cell turnover. In rats infected with Nippostrongylus brasiliensis, the flat mucosa has been shown to be due to the thymus-dependent immune response and not directly to the damage produced by the parasite itself. A common factor in the variety of conditions associated with villous atrophy and crypt hyperplasia may well be a local cell-mediated immune reaction to food, microbial, parasite or other antigens which causes changes in enterocyte turnover rate and malabsorption.", "contents": "Effects of local delayed hypersensitivity on the small intestine. There are many T and B cells in the small intestinal mucosa and local T cell immunity could have a role both in protective immunity and as a cause of disease (i.e. hypersensitivity). This latter aspect has been investigated by using several animal models to assess the effects of local delayed hypersensitivity on the structure and function of the small intestine. Heterotopically transplanted grafts of fetal small intestine in mice (isografts and allografts) have been examined by conventional histology, scanning and transmission electron microscopy, by making direct measurements of villi, crypts, and lymphoid cell infiltrate, and by counting the number of mitoses per crypt. This cell-mediated immune reaction causes lymphocyte infiltration which is most marked in the lamina propria, hyperplasia of the crypts of Lieberk\u00fchn, increased cell loss with villous atrophy and a flat surface, but the individual enterocytes appear fairly normal. Graft-versus-host disease cause exactly the same changes in structure and in cell kinetics as does rejection. However, crypt hyperplasia has been found to precede villous atrophy by several days. Preliminary experiments on local contact hypersensitivity suggest that intraluminal injection of oxazolone in the gut of sensitized mice also produces villous atrophy and crypt hyperplasia. It is postulated that these effects are likely to be produced via lymphokines: by an 'enteropathic' factor which damages the lamina propria and basement membrane, and a factor which is mitogenic for crypt stem cells. In mice infected with Giardia lamblia, crypt hyperplasia and lymphocyte infiltration of the epithelium are present and there is accelerated epithelial cell turnover. In rats infected with Nippostrongylus brasiliensis, the flat mucosa has been shown to be due to the thymus-dependent immune response and not directly to the damage produced by the parasite itself. A common factor in the variety of conditions associated with villous atrophy and crypt hyperplasia may well be a local cell-mediated immune reaction to food, microbial, parasite or other antigens which causes changes in enterocyte turnover rate and malabsorption."}
{"id": "PMID:25171", "title": "[Study of a beta-adrenergic stimulant and its antidepressant activity in man].", "content": "In animals, the psychopharmacological profile of beta-adrenergic stimulants is very similar to that of tricyclic antidepressants. In patients, more particularly in endogenous depressive patients, the antidepressant effect of salbutamol was very clear. A definite improvement was observed in all of the 22 studied patients after 1 to 3 days of intermittent venous infusion. The place of salbutamol in the therapeutic armamentarium of depressive states has still to be defined exactly. It is speculated that the antidepressant effect of imipramine-like derivatives is related to the stimulation of central beta 2-adrenergic receptors.", "contents": "[Study of a beta-adrenergic stimulant and its antidepressant activity in man]. In animals, the psychopharmacological profile of beta-adrenergic stimulants is very similar to that of tricyclic antidepressants. In patients, more particularly in endogenous depressive patients, the antidepressant effect of salbutamol was very clear. A definite improvement was observed in all of the 22 studied patients after 1 to 3 days of intermittent venous infusion. The place of salbutamol in the therapeutic armamentarium of depressive states has still to be defined exactly. It is speculated that the antidepressant effect of imipramine-like derivatives is related to the stimulation of central beta 2-adrenergic receptors."}
{"id": "PMID:25172", "title": "Apparent effects of neurotransmitters on sexual differentiation of the brain without mediation of sex hormones.", "content": "Male sexual behaviour was found to be permanently decreased in neonatally reserpinized or paragylinized male rats. On the other hand, hypoplasia of sex organs was only observed in reserpinized, but not in pargylinized newborn males. Furthermore, male sexual behavior was found to be permanently increased in neonatally pyridostigminized males which showed even a slight hypoplasia of seminal vesicles in neonatal life. These findings suggest that changes of neurotransmitter concentrations and/or turnover rates apparently induced by psychotrophic drugs can affect sex-specific brain differentiation by direct action without mediation of sex hormones. Hence, neurotransmitters may be regarded as organizers of the brain.", "contents": "Apparent effects of neurotransmitters on sexual differentiation of the brain without mediation of sex hormones. Male sexual behaviour was found to be permanently decreased in neonatally reserpinized or paragylinized male rats. On the other hand, hypoplasia of sex organs was only observed in reserpinized, but not in pargylinized newborn males. Furthermore, male sexual behavior was found to be permanently increased in neonatally pyridostigminized males which showed even a slight hypoplasia of seminal vesicles in neonatal life. These findings suggest that changes of neurotransmitter concentrations and/or turnover rates apparently induced by psychotrophic drugs can affect sex-specific brain differentiation by direct action without mediation of sex hormones. Hence, neurotransmitters may be regarded as organizers of the brain."}
{"id": "PMID:25173", "title": "Effects of total fasting in obese women. II. Acid-base balance.", "content": "Acetoacetate, beta-hydroxybutyrate, pyruvate and lactate in whole blood, the acid-base balance according to Astrup, SGOT and SGPT, and the serum and urinary sodium and potassium were estimated in 10 fasting obese women. Fasting led metabolic acidosis due to a tenfold increase of acetoacetate and beta-hydroxybutyrate, while pyruvate and lactate had a tendency to decrease. Serum and urinary sodium and potassium decreased; A tendency to increased SGOT and SGPT was observed. Sodium bicarbonate administered in general since the 8th or 9th day of fasting led in 4 to 5 days to an earlier correction of blood pH, while pCO2, actual HCO3, standard HCO3, base excess, buffer base, pO2, Hb saturation and total CO2 reached the prefasting values only several days after blood pH normalisation. The administration of NaHCO3 corrected the serum level of sodium while its excretion remained low. Bicarbonate had no influence on the decreasing trend of serum potassium, but the urinary output of potassium was stabilized. It is suggested that in fasting subjects 1. the correction of the metabolic acidosis by NaHCO3 does not reduce the rate of lipid catabolism and does not lead to fluid retention and 2. liver damage in fasting may be prevented by blood pH normalisation.", "contents": "Effects of total fasting in obese women. II. Acid-base balance. Acetoacetate, beta-hydroxybutyrate, pyruvate and lactate in whole blood, the acid-base balance according to Astrup, SGOT and SGPT, and the serum and urinary sodium and potassium were estimated in 10 fasting obese women. Fasting led metabolic acidosis due to a tenfold increase of acetoacetate and beta-hydroxybutyrate, while pyruvate and lactate had a tendency to decrease. Serum and urinary sodium and potassium decreased; A tendency to increased SGOT and SGPT was observed. Sodium bicarbonate administered in general since the 8th or 9th day of fasting led in 4 to 5 days to an earlier correction of blood pH, while pCO2, actual HCO3, standard HCO3, base excess, buffer base, pO2, Hb saturation and total CO2 reached the prefasting values only several days after blood pH normalisation. The administration of NaHCO3 corrected the serum level of sodium while its excretion remained low. Bicarbonate had no influence on the decreasing trend of serum potassium, but the urinary output of potassium was stabilized. It is suggested that in fasting subjects 1. the correction of the metabolic acidosis by NaHCO3 does not reduce the rate of lipid catabolism and does not lead to fluid retention and 2. liver damage in fasting may be prevented by blood pH normalisation."}
{"id": "PMID:25174", "title": "Effect of substrate composition and concentration on aortic cholesterol ester hydrolase activity.", "content": "Cholesterol ester hydrolase activity of pig aorta has been examined under optimum experimental conditions for hydrolysis of different cholesterol esters. The enzyme specific activity values were in the numerical order of substrates hydrolyzed: cholesteryl linoleate larger than or equal to linolenate greater than palmitate larger than or equal to stearate greater than oleate. The results are discussed in relation to the arterial accumulation of cholesterol esters.", "contents": "Effect of substrate composition and concentration on aortic cholesterol ester hydrolase activity. Cholesterol ester hydrolase activity of pig aorta has been examined under optimum experimental conditions for hydrolysis of different cholesterol esters. The enzyme specific activity values were in the numerical order of substrates hydrolyzed: cholesteryl linoleate larger than or equal to linolenate greater than palmitate larger than or equal to stearate greater than oleate. The results are discussed in relation to the arterial accumulation of cholesterol esters."}
{"id": "PMID:25175", "title": "Butadiene diepoxide activation of guanylate cyclase.", "content": "A variety of nitroso chemical carcinogens increase the activity of guanylate cyclase (EC 4.6.1.2), the enzyme catalyzing the production of guanosine 3',5'-monophosphate. In the present report, the first non-nitroso chemical carcinogen, butadiene diepoxide, was shown to activate guanylate in a variety of tissues over the concentration range 1-100 mmol/l. At 20 mmol/l concentration, increases were 2- to 17-fold above control. These observations have potential importance since guanosine 3',5'-monophosphate may be involved in cell growth and malignant transformation.", "contents": "Butadiene diepoxide activation of guanylate cyclase. A variety of nitroso chemical carcinogens increase the activity of guanylate cyclase (EC 4.6.1.2), the enzyme catalyzing the production of guanosine 3',5'-monophosphate. In the present report, the first non-nitroso chemical carcinogen, butadiene diepoxide, was shown to activate guanylate in a variety of tissues over the concentration range 1-100 mmol/l. At 20 mmol/l concentration, increases were 2- to 17-fold above control. These observations have potential importance since guanosine 3',5'-monophosphate may be involved in cell growth and malignant transformation."}
{"id": "PMID:25177", "title": "Purification and characterization of the two molecular forms of membrane acid protease from Aspergillus oryzae.", "content": "Two forms (M1 and M2) of the membrane-bound acid protease of Aspergillus oryzae have been purified by extraction with Triton X-100, washing with cold acetone, and repeated gel filtration on Bio-Gel A-15 m in the presence and absence of Triton X-100. The purified membrane enzymes, M1 and M2, moved as a single band in acrylamide gel electrophoresis and had apparent molecular weights of 150 000 and 60 000, respectively, as estimated by sodium dodecyl sulfate/acrylamide gel electrophoresis. These two membrane enzymes activated bovine pancreatic trypsinogen and had the same pH optima in the acid pH range. They immunologically cross-reacted with each other and with an extracellular acid protease from A. oryzae, and contained carbohydrate, ranging from 52.5 to 80.5% and comprising three hexoses, glucose, galactose, and mannose. While these catalytic, chemical and immunological properties are similar to those of the extracellular acid protease from A. oryzae, both membrane enzyme differed in their hydrophobic properties from external enzymes. Thus they are activated by the detergent Triton X-100 and some polar lipids.", "contents": "Purification and characterization of the two molecular forms of membrane acid protease from Aspergillus oryzae. Two forms (M1 and M2) of the membrane-bound acid protease of Aspergillus oryzae have been purified by extraction with Triton X-100, washing with cold acetone, and repeated gel filtration on Bio-Gel A-15 m in the presence and absence of Triton X-100. The purified membrane enzymes, M1 and M2, moved as a single band in acrylamide gel electrophoresis and had apparent molecular weights of 150 000 and 60 000, respectively, as estimated by sodium dodecyl sulfate/acrylamide gel electrophoresis. These two membrane enzymes activated bovine pancreatic trypsinogen and had the same pH optima in the acid pH range. They immunologically cross-reacted with each other and with an extracellular acid protease from A. oryzae, and contained carbohydrate, ranging from 52.5 to 80.5% and comprising three hexoses, glucose, galactose, and mannose. While these catalytic, chemical and immunological properties are similar to those of the extracellular acid protease from A. oryzae, both membrane enzyme differed in their hydrophobic properties from external enzymes. Thus they are activated by the detergent Triton X-100 and some polar lipids."}
{"id": "PMID:25179", "title": "Spectrofluorometric measurement of the binding of ethidium to superhelical DNA from cell nuclei.", "content": "Structures retaining many of the morphological features of nuclei may be released by lysing HeLa cells in solutions containing non-ionic detergents and high concentrations of salt. These nucleoids contain few chromatin proteins. We have shown that the DNA of nucleoids is quasicircular and supercoiled by measure spectrofluorometrically the amount of the intercalating dye, ethidium, bound to unirradiated and gamma-irradiated nucleoids. Ethidium binds to nucleoids in the manner characteristic of the binding to superhelical DNA: at low concentrations more ethidium binds to unirradiated nucleoids than to their gamma-irradiated counterparts with broken DNA, and at higher concentrations less ethidium binds to the unirradiated nucleoids. The quasi-circles in nucleoids are 22 times less sensitive to gamma-irradiation than are circles of pure PM2 DNA: they must contain about 2.2 X 10(5) base pairs. The constraints that maintain the quasi-circularity of nucleoid DNA are very resistant to extremes of temperature and alkali; some remain under conditions in which the duplex is denatured. The constraints are destabilised by ethidium suggesting that they are stabilised by free energy of supercoiling. Proteolytic enzymes, but not ribonucleases, remove the constraints. Possible structures for the constraining mechanism are discussed.", "contents": "Spectrofluorometric measurement of the binding of ethidium to superhelical DNA from cell nuclei. Structures retaining many of the morphological features of nuclei may be released by lysing HeLa cells in solutions containing non-ionic detergents and high concentrations of salt. These nucleoids contain few chromatin proteins. We have shown that the DNA of nucleoids is quasicircular and supercoiled by measure spectrofluorometrically the amount of the intercalating dye, ethidium, bound to unirradiated and gamma-irradiated nucleoids. Ethidium binds to nucleoids in the manner characteristic of the binding to superhelical DNA: at low concentrations more ethidium binds to unirradiated nucleoids than to their gamma-irradiated counterparts with broken DNA, and at higher concentrations less ethidium binds to the unirradiated nucleoids. The quasi-circles in nucleoids are 22 times less sensitive to gamma-irradiation than are circles of pure PM2 DNA: they must contain about 2.2 X 10(5) base pairs. The constraints that maintain the quasi-circularity of nucleoid DNA are very resistant to extremes of temperature and alkali; some remain under conditions in which the duplex is denatured. The constraints are destabilised by ethidium suggesting that they are stabilised by free energy of supercoiling. Proteolytic enzymes, but not ribonucleases, remove the constraints. Possible structures for the constraining mechanism are discussed."}
{"id": "PMID:25181", "title": "Characterization of beta-glucosidase isoenzymes possibly involved in lignification from chick pea (Cicer arietinum L.) cell suspension cultures.", "content": "Crude cell wall preparations from Cicer arietinum L. cell suspension cultures show high activity for the hydrolysis of coniferyl alcohol beta-D-glucoside (coniferin). Various beta-glucosidase activities could be solubilized from these preparations by 0.5 M NaCl treatment and one of these could be shown to possess a high activity for the hydrolysis of coniferin. The enzyme activities were purified to near homogeneity by Sephadex G-200 and CM-Sephadex chromatography. Isoelectric focussing indicated the occurrence of beta-glucosidase isoenzymes with identical catalytic activity (pI 8.5-10). Molecular weights were determined as 110 000, with two subunits of 63 000 and 43 000. Maximum hydrolytic activity is at pH 5. The beta-glucosidase isoenzymes catalyze the hydrolysis of various beta-glucosides with aromatic aglycone structure and different sugar moieties. However, coniferin has been found to be one of the best substrates (km = 0.8 mM; V = 6 mumol.min-1.mg protein-1) for these beta-glucosidase isoenzymes. The data suggest that beta-glucosidase-catalyzed reaction might be involved in lignification of these plant cell cultures.", "contents": "Characterization of beta-glucosidase isoenzymes possibly involved in lignification from chick pea (Cicer arietinum L.) cell suspension cultures. Crude cell wall preparations from Cicer arietinum L. cell suspension cultures show high activity for the hydrolysis of coniferyl alcohol beta-D-glucoside (coniferin). Various beta-glucosidase activities could be solubilized from these preparations by 0.5 M NaCl treatment and one of these could be shown to possess a high activity for the hydrolysis of coniferin. The enzyme activities were purified to near homogeneity by Sephadex G-200 and CM-Sephadex chromatography. Isoelectric focussing indicated the occurrence of beta-glucosidase isoenzymes with identical catalytic activity (pI 8.5-10). Molecular weights were determined as 110 000, with two subunits of 63 000 and 43 000. Maximum hydrolytic activity is at pH 5. The beta-glucosidase isoenzymes catalyze the hydrolysis of various beta-glucosides with aromatic aglycone structure and different sugar moieties. However, coniferin has been found to be one of the best substrates (km = 0.8 mM; V = 6 mumol.min-1.mg protein-1) for these beta-glucosidase isoenzymes. The data suggest that beta-glucosidase-catalyzed reaction might be involved in lignification of these plant cell cultures."}
{"id": "PMID:25186", "title": "Intrinsic sympathomimetic activity of beta-adrenoceptor blocking agents.", "content": "The pharmacological methods used to assess the intrinsic sympathomimetic activity (ISA) of beta-blockers are discussed. The clinical relevance of ISA to respiratory function, peripheral resistance and cardiac function is reviewed. It appears doubtful whether ISA is always of predominant clinical significance and an alternative explanation is offered for many clinical effects observed with certain beta-blockers, e.g. pindolol, oxprenolol, tolamolol, metoprolol, etc. Some effects of these beta-blockers resemble those of labetalol, a new drug with both alpha and beta-blocking activity. Some clinical effects of certain beta-blockers are more likely to be due to alpha-blocking activity than to their ISA.", "contents": "Intrinsic sympathomimetic activity of beta-adrenoceptor blocking agents. The pharmacological methods used to assess the intrinsic sympathomimetic activity (ISA) of beta-blockers are discussed. The clinical relevance of ISA to respiratory function, peripheral resistance and cardiac function is reviewed. It appears doubtful whether ISA is always of predominant clinical significance and an alternative explanation is offered for many clinical effects observed with certain beta-blockers, e.g. pindolol, oxprenolol, tolamolol, metoprolol, etc. Some effects of these beta-blockers resemble those of labetalol, a new drug with both alpha and beta-blocking activity. Some clinical effects of certain beta-blockers are more likely to be due to alpha-blocking activity than to their ISA."}
{"id": "PMID:25188", "title": "Effect of diazepam on the frog neuromuscular junction.", "content": "Diazepam (10(-5) M) had no effect on the compound action potential of frog sciatic nerve and its refractory period. At the neuromuscular junction, no changes were found in the amplitude and frequency of miniature endplate potentials in the presence of the drug. End-plate potential (e.p.p.) amplitude and early facilitation of the e.p.p. were unchanged. Diazepam had no effect on the amplitude of potentials evoked by ACh applied iontophoretically (0.1 Hz) at low frequencies in the chemosensitive region of the postjunctional membrane. Diazepam (10(-6) M) enhanced the progressive desensitization to ACh applied at a frequency of 1 Hz but did not affect recovery of sensitivity. A possible mechanism of action of diazepam at cholinergic synapses is discussed.", "contents": "Effect of diazepam on the frog neuromuscular junction. Diazepam (10(-5) M) had no effect on the compound action potential of frog sciatic nerve and its refractory period. At the neuromuscular junction, no changes were found in the amplitude and frequency of miniature endplate potentials in the presence of the drug. End-plate potential (e.p.p.) amplitude and early facilitation of the e.p.p. were unchanged. Diazepam had no effect on the amplitude of potentials evoked by ACh applied iontophoretically (0.1 Hz) at low frequencies in the chemosensitive region of the postjunctional membrane. Diazepam (10(-6) M) enhanced the progressive desensitization to ACh applied at a frequency of 1 Hz but did not affect recovery of sensitivity. A possible mechanism of action of diazepam at cholinergic synapses is discussed."}
{"id": "PMID:25190", "title": "Kinetics of blockade of different receptors by chlorpromazine in rabbit stomach strips.", "content": "The kinetics of receptor blockade by chlorpromazine (5 X 10(-8) M) were studied on fundic strips from the rabbit stomach. Onset of blockade by chlorpromazine proceeds at nearly identical rates when carbamylcholine and histamine are the agonists (t1/2 = approximately 5 min) while occurring more slowly against phenylephrine (t1/2 = 41 min). Similarly, offset of blockade by chlorpromazine is faster against carbamycholine and histamine (t1/2 = 83 and 34 min, respectively) than against phenylephrine (t1/2 = 385 min). The pA2 values of chlorpromazine on the alpha-adrenergic, muscarinic and histaminic (H1) receptors are 8.96, 7.17, and 7.90, respectively. No correlation  exists between the kinetics of blockade and the affinity of chlorpromazine for the receptors. It is suggested, therefore, that alpha-adrenoreceptors in the rabbit stomach are less accessible to chlorpromazine, or distributed differently within the tissue, than either the muscarinic or histaminic receptors.", "contents": "Kinetics of blockade of different receptors by chlorpromazine in rabbit stomach strips. The kinetics of receptor blockade by chlorpromazine (5 X 10(-8) M) were studied on fundic strips from the rabbit stomach. Onset of blockade by chlorpromazine proceeds at nearly identical rates when carbamylcholine and histamine are the agonists (t1/2 = approximately 5 min) while occurring more slowly against phenylephrine (t1/2 = 41 min). Similarly, offset of blockade by chlorpromazine is faster against carbamycholine and histamine (t1/2 = 83 and 34 min, respectively) than against phenylephrine (t1/2 = 385 min). The pA2 values of chlorpromazine on the alpha-adrenergic, muscarinic and histaminic (H1) receptors are 8.96, 7.17, and 7.90, respectively. No correlation  exists between the kinetics of blockade and the affinity of chlorpromazine for the receptors. It is suggested, therefore, that alpha-adrenoreceptors in the rabbit stomach are less accessible to chlorpromazine, or distributed differently within the tissue, than either the muscarinic or histaminic receptors."}
{"id": "PMID:25191", "title": "Benzodiazepine receptors: labeling in intact animals with [3H] flunitrazepam.", "content": "[3H]Flumitrazepam appears to label specific benzodiazepine receptors in vitro after i.v. injection in mice. Benzodiazepine potencies in reducing [3H]flunitrazepam binding in vivo correspond to pharmacological potencies and parallel relative affinites for [3H]flunitrazepam binding sites in isolated brain membranes. However, 50% occupation of [3H]-flunitrazepam sites by benzodiazepines in vivo requires brain concentrations of the drugs about 1000 times higher than their Ki values for the binding sites in vitro. In pharmacologically active doses sodium pentobarbital, strychnine, picrotoxin and bicuculline fail to influence [3H] flunitrazepam binding in vivo.", "contents": "Benzodiazepine receptors: labeling in intact animals with [3H] flunitrazepam. [3H]Flumitrazepam appears to label specific benzodiazepine receptors in vitro after i.v. injection in mice. Benzodiazepine potencies in reducing [3H]flunitrazepam binding in vivo correspond to pharmacological potencies and parallel relative affinites for [3H]flunitrazepam binding sites in isolated brain membranes. However, 50% occupation of [3H]-flunitrazepam sites by benzodiazepines in vivo requires brain concentrations of the drugs about 1000 times higher than their Ki values for the binding sites in vitro. In pharmacologically active doses sodium pentobarbital, strychnine, picrotoxin and bicuculline fail to influence [3H] flunitrazepam binding in vivo."}
{"id": "PMID:25194", "title": "Amnesic effects of intravenous diazepam and lorazepam.", "content": "The amnesic effects of 2 benzodiazepine drugs, diazepam (Valium) and lorazepam (Ativan), have been investigated. Some of the effects were similar to those of certain clinical amnesic syndromes. The effects were more extensive than previous work has indicated.", "contents": "Amnesic effects of intravenous diazepam and lorazepam. The amnesic effects of 2 benzodiazepine drugs, diazepam (Valium) and lorazepam (Ativan), have been investigated. Some of the effects were similar to those of certain clinical amnesic syndromes. The effects were more extensive than previous work has indicated."}
{"id": "PMID:25195", "title": "Neutral proteases in the guinea-pig lymphocytes.", "content": "Partial purification of neutral proteolytic enzymes in guinea-pig lymphocytes yielded 2 enzymes. Both enzymes were heat-labile and inhibited by thiol reagents. The molecular weights were more than 200,000 and 150,000-200,000, and optimal pH around 9 and 8, respectively.", "contents": "Neutral proteases in the guinea-pig lymphocytes. Partial purification of neutral proteolytic enzymes in guinea-pig lymphocytes yielded 2 enzymes. Both enzymes were heat-labile and inhibited by thiol reagents. The molecular weights were more than 200,000 and 150,000-200,000, and optimal pH around 9 and 8, respectively."}
{"id": "PMID:25197", "title": "Effect of age on T cell differentiation.", "content": "A brief overview of the area of T cell aging is presented by first discussing the age-related changes in T cell activities, and then by focusing attention on the possible mechanisms that may be responsible for the decline. Present evidence indicates that thymic involution precedes and therefore may be responsible for the age-dependent decline in the ability of the immune system to generate functional T cells. At this time, it appears that the primary effect of thymic involution is on a T cell differentiation pathway affecting the more mature T cells first with time, and then the less mature T cells. Thus, the thymus may be the aging clock for the immune system. Further studies should be centered around processes regulating growth and atrophy of the thymus.", "contents": "Effect of age on T cell differentiation. A brief overview of the area of T cell aging is presented by first discussing the age-related changes in T cell activities, and then by focusing attention on the possible mechanisms that may be responsible for the decline. Present evidence indicates that thymic involution precedes and therefore may be responsible for the age-dependent decline in the ability of the immune system to generate functional T cells. At this time, it appears that the primary effect of thymic involution is on a T cell differentiation pathway affecting the more mature T cells first with time, and then the less mature T cells. Thus, the thymus may be the aging clock for the immune system. Further studies should be centered around processes regulating growth and atrophy of the thymus."}
{"id": "PMID:25215", "title": "Nasal absorption of insulin in dogs.", "content": "The intranasal application of an insulin solution in dogs resulted in the rise of plasma immunoreactive insulin and in dose-dependent hypoglycemia. The absorption of insulin from this site was found to be enhanced when insulin was dissolved in an acid medium. In addition, when an insulin preparation with some surfactant was used, the effectiveness of nasally administered insulin was 25 to 30 per cent of that achieved with intravenously administered insulin.", "contents": "Nasal absorption of insulin in dogs. The intranasal application of an insulin solution in dogs resulted in the rise of plasma immunoreactive insulin and in dose-dependent hypoglycemia. The absorption of insulin from this site was found to be enhanced when insulin was dissolved in an acid medium. In addition, when an insulin preparation with some surfactant was used, the effectiveness of nasally administered insulin was 25 to 30 per cent of that achieved with intravenously administered insulin."}
{"id": "PMID:25217", "title": "Trial of an alpha-adrenolytic drug (indoramin) for nocturnal enuresis.", "content": "The investigation of methods of treatment known to be effective in controlling nocturnal enuresis may yield information on the pathophysiology of the condition. An attempt has been made to mimic the known alpha-adrenolytic action of imipramine by treating a group of 14 enuretic school-children with a competitive alpha-adrenoceptor blocking substance, indoramin. Treatment in the doses used had no significant effect on night-wetting frequency.", "contents": "Trial of an alpha-adrenolytic drug (indoramin) for nocturnal enuresis. The investigation of methods of treatment known to be effective in controlling nocturnal enuresis may yield information on the pathophysiology of the condition. An attempt has been made to mimic the known alpha-adrenolytic action of imipramine by treating a group of 14 enuretic school-children with a competitive alpha-adrenoceptor blocking substance, indoramin. Treatment in the doses used had no significant effect on night-wetting frequency."}
{"id": "PMID:25218", "title": "Intestinal mucins in health and disease.", "content": "Intestinal mucins are complex glycoproteins which are secreted from goblet cells, and form a gel-like covering over the mucosal surface. They are assumed to provide lubrication and protection of the underlying epithelium against potentially injurious chemicals, enzymes, bacteria and dietary constituents. Recent advances in our understanding of mucin structure, secretion and functional properties are reviewed in this paper. Implications for diseases such as cystic fibrosis, peptic ulcer, malignancy and inflammatory bowel disease are briefly discussed.", "contents": "Intestinal mucins in health and disease. Intestinal mucins are complex glycoproteins which are secreted from goblet cells, and form a gel-like covering over the mucosal surface. They are assumed to provide lubrication and protection of the underlying epithelium against potentially injurious chemicals, enzymes, bacteria and dietary constituents. Recent advances in our understanding of mucin structure, secretion and functional properties are reviewed in this paper. Implications for diseases such as cystic fibrosis, peptic ulcer, malignancy and inflammatory bowel disease are briefly discussed."}
{"id": "PMID:25221", "title": "Prognosis in children with Crohn's disease.", "content": "The course of 86 children with Crohn's disease was examined during a 10-year period between 1966 and 1976. Patients were classified according to the initial site of disease. Ileocolitis was the most (52%) and colitis the least (9%) common form of disease with diffuse small bowel or ileal disease each comprising nearly 20% of the study group. These figures show a reversal from those of a previous decade when 42% of the patients had only terminal ileal disease and 17% had ileocolitis. Children with ileocolitis had the highest number of extracolonic manifestations and operations and required steroid therapy the longest. Those with only small bowel disease (with the exception of duodenal involvement) had fewer extraintestinal symptoms and operations and showed a consistently good response to medical treatment.", "contents": "Prognosis in children with Crohn's disease. The course of 86 children with Crohn's disease was examined during a 10-year period between 1966 and 1976. Patients were classified according to the initial site of disease. Ileocolitis was the most (52%) and colitis the least (9%) common form of disease with diffuse small bowel or ileal disease each comprising nearly 20% of the study group. These figures show a reversal from those of a previous decade when 42% of the patients had only terminal ileal disease and 17% had ileocolitis. Children with ileocolitis had the highest number of extracolonic manifestations and operations and required steroid therapy the longest. Those with only small bowel disease (with the exception of duodenal involvement) had fewer extraintestinal symptoms and operations and showed a consistently good response to medical treatment."}
{"id": "PMID:25222", "title": "Inhibition of pancreatic secretion by enkephalin and morphine in dogs.", "content": "The nature and extent of enkephalin- and morphine-induced inhibition of pancreatic bicarbonate and protein secretion were studied in dogs with chronic pancreatic fistulae after administering exogenous secretin or octapeptide of cholecystokinin and stimulants for the endogenous release of these hormones. Enkephalin and morphine competitively inhibited the pancreatic bicarbonate secretion induced either by exogenous secretin or duodenal acidification. This inhibition was partially reversed by naloxone, an opiate antagonist. Opiate substance also profoundly inhibited pancreatic protein response to octapeptide of cholecystokinin and to various stimulants of endogenous cholecystokinin release. We conclude that enkephalin and morphine strongly inhibit the pancreatic responses to exogenous and endogenous stimulants by a mechanism involving separate opiate receptors.", "contents": "Inhibition of pancreatic secretion by enkephalin and morphine in dogs. The nature and extent of enkephalin- and morphine-induced inhibition of pancreatic bicarbonate and protein secretion were studied in dogs with chronic pancreatic fistulae after administering exogenous secretin or octapeptide of cholecystokinin and stimulants for the endogenous release of these hormones. Enkephalin and morphine competitively inhibited the pancreatic bicarbonate secretion induced either by exogenous secretin or duodenal acidification. This inhibition was partially reversed by naloxone, an opiate antagonist. Opiate substance also profoundly inhibited pancreatic protein response to octapeptide of cholecystokinin and to various stimulants of endogenous cholecystokinin release. We conclude that enkephalin and morphine strongly inhibit the pancreatic responses to exogenous and endogenous stimulants by a mechanism involving separate opiate receptors."}
{"id": "PMID:25227", "title": "Some further characteristics of the growth of Naegleria fowleri and N. gruberi in axenic culture.", "content": "The effects of pH, various viscosity of the medium, changed ratio between the concentrations of dissolved and corpuscular components in the medium, and dissolved inorganic salts on the growth of axenic cultures of Naegleria fowleri and N. gruberi have been studied. The cultures were grown in liquid CALYG and BCS media. The pH optimum was 6.5 for N. fowleri and 6.0--6.5 for N. gruberi. No negative influence on the growth of N. fowleri was observed even at 0.5% concentration of highly viscous methylcellulose, whereas the growth of N. gruberi was distinctly inhibited by more than 0.2% of methycellulose. N. fowleri preferred the osmotorphic and N. gruberi phagotrophic nutrition in the given system of cultivation. The growth of both Naegleria species was inhibited by 0.1 N concentration of sodium chloride and potassium chloride without any significant difference in the tolerance. The inhibitory effect of these salts correlated primarily with the concentration of chloride anion. The ability to grow in a medium with increased viscosity and the preference for osmotrophic nutrtion are, besides the higher temperature optimum determined earlier, further characteristics of the pathogenic species N. fowleri.", "contents": "Some further characteristics of the growth of Naegleria fowleri and N. gruberi in axenic culture. The effects of pH, various viscosity of the medium, changed ratio between the concentrations of dissolved and corpuscular components in the medium, and dissolved inorganic salts on the growth of axenic cultures of Naegleria fowleri and N. gruberi have been studied. The cultures were grown in liquid CALYG and BCS media. The pH optimum was 6.5 for N. fowleri and 6.0--6.5 for N. gruberi. No negative influence on the growth of N. fowleri was observed even at 0.5% concentration of highly viscous methylcellulose, whereas the growth of N. gruberi was distinctly inhibited by more than 0.2% of methycellulose. N. fowleri preferred the osmotorphic and N. gruberi phagotrophic nutrition in the given system of cultivation. The growth of both Naegleria species was inhibited by 0.1 N concentration of sodium chloride and potassium chloride without any significant difference in the tolerance. The inhibitory effect of these salts correlated primarily with the concentration of chloride anion. The ability to grow in a medium with increased viscosity and the preference for osmotrophic nutrtion are, besides the higher temperature optimum determined earlier, further characteristics of the pathogenic species N. fowleri."}
{"id": "PMID:25228", "title": "Virological examination of mosquito larvae from southern Moravia.", "content": "254 pools of 4,115 mosquito larvae belonging to nine species were examined by isolation experiments. The larvae were collected in breeding places in an inundated forest--a natural focus of Tahyna virus, in April, June and July 1974 and 1975. Tahyna virus was isolated from one pool of 10 Culiseta annulata larvae collected in July 1974. Ecological questions concerning this finding are discussed.", "contents": "Virological examination of mosquito larvae from southern Moravia. 254 pools of 4,115 mosquito larvae belonging to nine species were examined by isolation experiments. The larvae were collected in breeding places in an inundated forest--a natural focus of Tahyna virus, in April, June and July 1974 and 1975. Tahyna virus was isolated from one pool of 10 Culiseta annulata larvae collected in July 1974. Ecological questions concerning this finding are discussed."}
{"id": "PMID:25229", "title": "[Electroencephalographic effects of flurazepam in rabbits (author's transl)].", "content": "Electroencephalographic (EEG) effects of flurazepam were investigated in unanesthetized, unrestrained rabbits with chronic electrode implants and compared with those of diazepam. Flurazepam, at doses of 0.5 approximately 5 mg/kg i.v., induced a drowsy EEG pattern, i.e. high voltage slow waves in the cortex and amygdaloid complex and desynchronization of the hippocampal theta waves. In addition, low voltage fast waves were superimposed, especially on the cortical EEG. Flurazepam suppressed the EEG arousal responses induced not only by auditory stimulation but also by electrical stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus. The EEG arousal response induced by i.v. injection of physostigmine was suppressed by flurazepam. Flurazepam depressed the photic driving response and the augmenting response. The recruiting response was slightly enhanced by flurazepam. The limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation were suppressed by flurazepam. Flurazepam caused reductions of pressor responses to stimulation of the posterior hypothalamus and the mesencephalic reticular formation in anaesthetized rabbits. There was little or no effect on pressor responses to the injection of noradrenaline, carotid artery occulusion and asphyxia with flurazepam. In general, these effects of flurazepam were similar to those of diazepam, but the drug induced actions which differed from those of diazepam.", "contents": "[Electroencephalographic effects of flurazepam in rabbits (author's transl)]. Electroencephalographic (EEG) effects of flurazepam were investigated in unanesthetized, unrestrained rabbits with chronic electrode implants and compared with those of diazepam. Flurazepam, at doses of 0.5 approximately 5 mg/kg i.v., induced a drowsy EEG pattern, i.e. high voltage slow waves in the cortex and amygdaloid complex and desynchronization of the hippocampal theta waves. In addition, low voltage fast waves were superimposed, especially on the cortical EEG. Flurazepam suppressed the EEG arousal responses induced not only by auditory stimulation but also by electrical stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus. The EEG arousal response induced by i.v. injection of physostigmine was suppressed by flurazepam. Flurazepam depressed the photic driving response and the augmenting response. The recruiting response was slightly enhanced by flurazepam. The limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation were suppressed by flurazepam. Flurazepam caused reductions of pressor responses to stimulation of the posterior hypothalamus and the mesencephalic reticular formation in anaesthetized rabbits. There was little or no effect on pressor responses to the injection of noradrenaline, carotid artery occulusion and asphyxia with flurazepam. In general, these effects of flurazepam were similar to those of diazepam, but the drug induced actions which differed from those of diazepam."}
{"id": "PMID:25230", "title": "[Comparative studies of antihypertensive effects of several beta-blocking agents in conscious rats (author's transl)].", "content": "The present study was undertaken to compare the antihypertensive effects of beta-blocking agents and to clarify the relations between antihypertensive effects and beta-blocking actions. In this study, blood pressure was measured by a direct cannulation of the abdominal aorta. Subcutaneous administration of carteolol and pindolol caused a significant fall in mean blood pressure in both normotensive and spontaneously hypertensive rats, whereas propranolol produced a rise in blood pressure. Maximum fall in blood pressure was observed 3 approximately 7 hr after the administration of carteolol and pindolol. In order to determine the beta-blocking action, changes in heart rate and blood pressure in response to isoproterenol (3 microgram/kg i.v.) were observed during the experiment. beta-Blocking action was found as early as 1 hr after subcutaneous administration. Carteolol showed the most effective blocking action throughout the experiment. Although beta-blocking agents lowered the blood pressure in this experiment, there was no apparent parallel between antihypertensive effects and beta-blocking action on the cardiac function.", "contents": "[Comparative studies of antihypertensive effects of several beta-blocking agents in conscious rats (author's transl)]. The present study was undertaken to compare the antihypertensive effects of beta-blocking agents and to clarify the relations between antihypertensive effects and beta-blocking actions. In this study, blood pressure was measured by a direct cannulation of the abdominal aorta. Subcutaneous administration of carteolol and pindolol caused a significant fall in mean blood pressure in both normotensive and spontaneously hypertensive rats, whereas propranolol produced a rise in blood pressure. Maximum fall in blood pressure was observed 3 approximately 7 hr after the administration of carteolol and pindolol. In order to determine the beta-blocking action, changes in heart rate and blood pressure in response to isoproterenol (3 microgram/kg i.v.) were observed during the experiment. beta-Blocking action was found as early as 1 hr after subcutaneous administration. Carteolol showed the most effective blocking action throughout the experiment. Although beta-blocking agents lowered the blood pressure in this experiment, there was no apparent parallel between antihypertensive effects and beta-blocking action on the cardiac function."}
{"id": "PMID:25231", "title": "[Pharmacological studies of loperamide, an anti-diarrheal agent. I. Effects on diarrhea induced by castor oil and prostaglandin E. (author's transl)].", "content": "Effects of loperamide on diarrhea induced by castor oil and prostaglandin E1 were investigated in rats and mice and compared with those of narcotic analgesics, atropine, mecamylamine and local anesthetics. The following results were obtained. Loperamide markedly suppressed the appearance of diarrhea induced by oral administration of castor oil in rats and the ED50 values for 1 and 2 hr protection was 0.082 and 0.42 mg/kg p.o., respectively. Loperamide markedly suppressed the appearance of diarrhea induced by i.v. administration of prostaglandin E1 and the ED50 value for 2 hr protection was 0.24 mg/kg p.o. in rats. The ID120 min value of loperamide which was calculated on the basis of the dose producing a 20% or more inhibition of the charcoal transport in the small intestine for 120 min was 0.8 mg/kg p.o. in mice and this activity was 9.2 times more potent than that of morphine. The analgesic ED50 value (Haffner's method) and LD50 value of loperamide was 149 and 249 mg/kg p.o., respectively. These results suggest that loperamide has a potent anti-diarrheal activity and specificity to the gastrointestinal tract and inhibits the effect of prostaglandin E1 and ricinoleic acid on the intestinal tract in rats.", "contents": "[Pharmacological studies of loperamide, an anti-diarrheal agent. I. Effects on diarrhea induced by castor oil and prostaglandin E. (author's transl)]. Effects of loperamide on diarrhea induced by castor oil and prostaglandin E1 were investigated in rats and mice and compared with those of narcotic analgesics, atropine, mecamylamine and local anesthetics. The following results were obtained. Loperamide markedly suppressed the appearance of diarrhea induced by oral administration of castor oil in rats and the ED50 values for 1 and 2 hr protection was 0.082 and 0.42 mg/kg p.o., respectively. Loperamide markedly suppressed the appearance of diarrhea induced by i.v. administration of prostaglandin E1 and the ED50 value for 2 hr protection was 0.24 mg/kg p.o. in rats. The ID120 min value of loperamide which was calculated on the basis of the dose producing a 20% or more inhibition of the charcoal transport in the small intestine for 120 min was 0.8 mg/kg p.o. in mice and this activity was 9.2 times more potent than that of morphine. The analgesic ED50 value (Haffner's method) and LD50 value of loperamide was 149 and 249 mg/kg p.o., respectively. These results suggest that loperamide has a potent anti-diarrheal activity and specificity to the gastrointestinal tract and inhibits the effect of prostaglandin E1 and ricinoleic acid on the intestinal tract in rats."}
{"id": "PMID:25232", "title": "[Mechanism of methamphetamine toxicity in grouped mice and the effects of centrally acting drugs on its toxicity (author's transl)].", "content": "The mortality of ddK mice treated with 40 mg/kg i.p. of methamphetamine (MA) was 85% in grouped conditions (10 mice in a cage) and 3% in individually isolated conditions. This mortality was not altered by the social environments even when other mice in the cage were not treated with MA. The mortality of mice individually isolated in cages with transparent walls was significantly higher than that of completely isolated mice. Almost all neuroleptics dose-dependently antagonized the MA toxicity in grouped mice, in small doses. The antagonizing activity of clozapine was somewhat weak, and sulpiride potentiated MA toxicity. Phentolamine and propranolol antagonized the MA toxicity at higher doses than neuroleptics. Reserpine and tetrabenazine previously given to mice remarkably antagonized the MA toxicity. H44/68 (a tyrosine hydroxylase inhibitor) had a considerable effect in antagonizing the MA toxicity, but diethyldithiocarbamate, U-14, 624 and FLA 63 (dopamine-beta-hydroxylase inhibitors) prevented the MA toxicity to a lesser extent than did H44/68. Apomorphine had no effect on the MA toxicity. The present data show that the MA toxicity in grouped mice (the increase in mortality) was enhanced by the presence of other mice, and suggest that the norepinephrine neurons play an important role in promoting the MA toxicity. Neuroleptics antagonize MA toxicity probably by blocking alpha-receptors in the central nervous system.", "contents": "[Mechanism of methamphetamine toxicity in grouped mice and the effects of centrally acting drugs on its toxicity (author's transl)]. The mortality of ddK mice treated with 40 mg/kg i.p. of methamphetamine (MA) was 85% in grouped conditions (10 mice in a cage) and 3% in individually isolated conditions. This mortality was not altered by the social environments even when other mice in the cage were not treated with MA. The mortality of mice individually isolated in cages with transparent walls was significantly higher than that of completely isolated mice. Almost all neuroleptics dose-dependently antagonized the MA toxicity in grouped mice, in small doses. The antagonizing activity of clozapine was somewhat weak, and sulpiride potentiated MA toxicity. Phentolamine and propranolol antagonized the MA toxicity at higher doses than neuroleptics. Reserpine and tetrabenazine previously given to mice remarkably antagonized the MA toxicity. H44/68 (a tyrosine hydroxylase inhibitor) had a considerable effect in antagonizing the MA toxicity, but diethyldithiocarbamate, U-14, 624 and FLA 63 (dopamine-beta-hydroxylase inhibitors) prevented the MA toxicity to a lesser extent than did H44/68. Apomorphine had no effect on the MA toxicity. The present data show that the MA toxicity in grouped mice (the increase in mortality) was enhanced by the presence of other mice, and suggest that the norepinephrine neurons play an important role in promoting the MA toxicity. Neuroleptics antagonize MA toxicity probably by blocking alpha-receptors in the central nervous system."}
{"id": "PMID:25233", "title": "[Digestant effects of a new digestive enzyme capsule, Excelase, on jejunectomized and pancreato-jejunectomized Beagle dogs (author's transl)].", "content": "The digestant effects of a new digestive capsule, excelase containing sanactase, proctase, meicelase, olipase-2S and pancreatic digestive enzyme TA, were investigated in vivo. Jejunectomy and pancreato-jejunectomy were performed to cause an artificial disturbance of gastro-intestinal digestion and absorption in Beagle dogs. Absorption of protein and fat was measured using chromic oxide as an indicator. Excelase (3 capsules/dog/day) was given orally to Beagle dogs 1 week after each operation for 7 weeks. Changes in body weight and absorption of protein and fat were observed during the administration. The decrease in body weight of dogs treated with excelase fully recovered, however, that of controls remained even 8 weeks after the surgery. Absorption of protein and fat in the groups of dogs treated with excelase was greatly improved as compared with controls. The digestant effects of excelase on percent absorption of protein and fat were more manifest in pancreato-jejunectomized dogs than in jejunectomized dogs. These results indicate that excelase is effective for gastro-intestinal disturbances of digestion and absorption. The digestant effects of excelase on starch, protein and cellulose were also investigated in vitro using a gastro-intestinal model.", "contents": "[Digestant effects of a new digestive enzyme capsule, Excelase, on jejunectomized and pancreato-jejunectomized Beagle dogs (author's transl)]. The digestant effects of a new digestive capsule, excelase containing sanactase, proctase, meicelase, olipase-2S and pancreatic digestive enzyme TA, were investigated in vivo. Jejunectomy and pancreato-jejunectomy were performed to cause an artificial disturbance of gastro-intestinal digestion and absorption in Beagle dogs. Absorption of protein and fat was measured using chromic oxide as an indicator. Excelase (3 capsules/dog/day) was given orally to Beagle dogs 1 week after each operation for 7 weeks. Changes in body weight and absorption of protein and fat were observed during the administration. The decrease in body weight of dogs treated with excelase fully recovered, however, that of controls remained even 8 weeks after the surgery. Absorption of protein and fat in the groups of dogs treated with excelase was greatly improved as compared with controls. The digestant effects of excelase on percent absorption of protein and fat were more manifest in pancreato-jejunectomized dogs than in jejunectomized dogs. These results indicate that excelase is effective for gastro-intestinal disturbances of digestion and absorption. The digestant effects of excelase on starch, protein and cellulose were also investigated in vitro using a gastro-intestinal model."}
{"id": "PMID:25234", "title": "[Relation between the drug-metabolizing activities of liver microsomes and multiplicity of cytochrome P-450 (author's transl)].", "content": "Wada et al. found a hyperbolic curve in the Lineweaver-Burk plots of the drug-metabolizing activity and competitive inhibition of steroid hormones to drugs, and suggested that several enzymes acting on different sites of various steroid hormone molecules might metabolize drugs without having specificities for hydroxylation sites. Recently, several cytochrome P-450s were separated and purified from liver microsomes. We studied the relation between the drug-metabolizing activities and multiplicity of cytochrome P-450 with the pH curve and the Lineweaver-Burk plots. Phenobarbital- and methylcholanthrene-treatment had remarkable effects on the pH curve of aniline hydroxylation by mouse liver microsomes. Addition of cortisol inhibited aniline hydroxylatin by liver microsomes from phenobarbital-treated mice more effectively at higher pH range and the pH curve was similar to that seen for normal mice. Haugen and Coon separated preparations [A] [B] and [C] with hydroxylapatite chromatography and we obtained [A'] (eluted by 100 mM K-phosphate buffer, pH 7.4) between [A] (50 mM) and [B] (300 mM). The preparation [A'] had the same absorption maximum (451 nm) of reduced CO complex as [A], but Km and pH curve for [A'] were similar to those for [B]. Each separated preparation of cytochrome P-450 showed a hyperbolic curve in Lineweaver-Burk plots and a different pH curve from each other.", "contents": "[Relation between the drug-metabolizing activities of liver microsomes and multiplicity of cytochrome P-450 (author's transl)]. Wada et al. found a hyperbolic curve in the Lineweaver-Burk plots of the drug-metabolizing activity and competitive inhibition of steroid hormones to drugs, and suggested that several enzymes acting on different sites of various steroid hormone molecules might metabolize drugs without having specificities for hydroxylation sites. Recently, several cytochrome P-450s were separated and purified from liver microsomes. We studied the relation between the drug-metabolizing activities and multiplicity of cytochrome P-450 with the pH curve and the Lineweaver-Burk plots. Phenobarbital- and methylcholanthrene-treatment had remarkable effects on the pH curve of aniline hydroxylation by mouse liver microsomes. Addition of cortisol inhibited aniline hydroxylatin by liver microsomes from phenobarbital-treated mice more effectively at higher pH range and the pH curve was similar to that seen for normal mice. Haugen and Coon separated preparations [A] [B] and [C] with hydroxylapatite chromatography and we obtained [A'] (eluted by 100 mM K-phosphate buffer, pH 7.4) between [A] (50 mM) and [B] (300 mM). The preparation [A'] had the same absorption maximum (451 nm) of reduced CO complex as [A], but Km and pH curve for [A'] were similar to those for [B]. Each separated preparation of cytochrome P-450 showed a hyperbolic curve in Lineweaver-Burk plots and a different pH curve from each other."}
{"id": "PMID:25237", "title": "[Comparative studies on the protective effect of etilefrin and dihydroergotamine in circulatory instability after blood donation].", "content": "In 20 female and 40 male subjects with circulatory instability, the response of pulse rate and blood pressure to blood loss and orthostasis was studied under the condition of protective pretreatment with drugs known to improve venous return by increasing the tone of capacitance vessels. Before blood loss (420 ml), in a cross-over double-blind procedure, each subject obtained 10 mg etilefrin or 2 mg dihydroergotamine, both administered orally. The procedure was repeated after at least 8 weeks. At this time, the subject obtained the drug which was not given in the first examination. By comparison of pulse rate and blood pressure taken after pretreatment, the statistical evaluation did not reveal any differences in the effectiveness of one or the other drug on the response to hypovolemic and orthostatic conditions. Patients preferred etilefrin.", "contents": "[Comparative studies on the protective effect of etilefrin and dihydroergotamine in circulatory instability after blood donation]. In 20 female and 40 male subjects with circulatory instability, the response of pulse rate and blood pressure to blood loss and orthostasis was studied under the condition of protective pretreatment with drugs known to improve venous return by increasing the tone of capacitance vessels. Before blood loss (420 ml), in a cross-over double-blind procedure, each subject obtained 10 mg etilefrin or 2 mg dihydroergotamine, both administered orally. The procedure was repeated after at least 8 weeks. At this time, the subject obtained the drug which was not given in the first examination. By comparison of pulse rate and blood pressure taken after pretreatment, the statistical evaluation did not reveal any differences in the effectiveness of one or the other drug on the response to hypovolemic and orthostatic conditions. Patients preferred etilefrin."}
{"id": "PMID:25241", "title": "Macrophage colony development: properties of colony stimulating factors from murine embryo and pregnant uterus.", "content": "Extracts from embryonic and uterine tissue of mice, operationally defined as colony stimulating factor (CSF), promoted the growth of macrophage-granulocyte colonies in vitro. Uterine CSF focusses from pH 5.15 to 6.00 and embryonic CSF from pH 3.60 to 5.20, although both forms have similar biological activity. CSF is relatively resistant to denaturation but it is inactivated by periodate and dithiothreitol. Gel filtration indicates a molecular weight of 45,000 which is unchanged following treatment with insolubilized trypsin, a procedure which affords a useful purification (240-fold). Trypsin-sensitive material in CSF preparations modifies colonial form under certain conditions of culture, probably by increasing the motility of macrophages. Diaminoethane derivatives of CSF were prepared and retained biological activity at isoelectric points above pH 9.0. These derivatives may be covalently linked to Sepharose providing an insolubilized form of CSF to study interactions of CSF with the cell surface.", "contents": "Macrophage colony development: properties of colony stimulating factors from murine embryo and pregnant uterus. Extracts from embryonic and uterine tissue of mice, operationally defined as colony stimulating factor (CSF), promoted the growth of macrophage-granulocyte colonies in vitro. Uterine CSF focusses from pH 5.15 to 6.00 and embryonic CSF from pH 3.60 to 5.20, although both forms have similar biological activity. CSF is relatively resistant to denaturation but it is inactivated by periodate and dithiothreitol. Gel filtration indicates a molecular weight of 45,000 which is unchanged following treatment with insolubilized trypsin, a procedure which affords a useful purification (240-fold). Trypsin-sensitive material in CSF preparations modifies colonial form under certain conditions of culture, probably by increasing the motility of macrophages. Diaminoethane derivatives of CSF were prepared and retained biological activity at isoelectric points above pH 9.0. These derivatives may be covalently linked to Sepharose providing an insolubilized form of CSF to study interactions of CSF with the cell surface."}
{"id": "PMID:25242", "title": "Effect of complement fixation on the release of lysosomal enzymes from rabbit alveolar macrophages.", "content": "Macrophage lysosomal enzymes that have specificities for substrates found in mammalian tissue may contribute to the tissue damage observed in chronic inflammatory diseases. Although a variety of agents that stimulate the release of hydrolases from peritoneal macrophages have been identified, little work has been done to establish the conditions and specific stimuli responsible for enzyme release by alveolar macrophages (AM). To assess the effect of phagocytosis by AM on the release phenomenon, hydrolytic enzymes normally sequestered in AM lysosomes were quantified in the supernatant fluids of phagocytosing and non-phagocytosing AM monolayers in both the presence and absence of serum. Maximum release occurred under conditions known to favor complement fixation by the classical or alternative pathways. Thermal destruction or immune fixation of serum complement before use in culture reduced the magnitude of release to that observed in cultures incubated in the complete absence of serum. Phagocytosis was not essential for release, since cells exposed to particles but treated with a known inhibitor of phagocytosis (cytochalasin B) still showed maximal release in the presence of fresh serum. These data are interpreted to indicate that a heat-labile component of serum, probably a by-product of complement fixation, was primarily responsible for the hydrolase release by AM. On the basis of these findings, individuals suffering from chronic pulmonary disease may suffer acute episodes of lung destruction from endogenous AM enzymes upon the inhalation of materials capable of fixing complement.", "contents": "Effect of complement fixation on the release of lysosomal enzymes from rabbit alveolar macrophages. Macrophage lysosomal enzymes that have specificities for substrates found in mammalian tissue may contribute to the tissue damage observed in chronic inflammatory diseases. Although a variety of agents that stimulate the release of hydrolases from peritoneal macrophages have been identified, little work has been done to establish the conditions and specific stimuli responsible for enzyme release by alveolar macrophages (AM). To assess the effect of phagocytosis by AM on the release phenomenon, hydrolytic enzymes normally sequestered in AM lysosomes were quantified in the supernatant fluids of phagocytosing and non-phagocytosing AM monolayers in both the presence and absence of serum. Maximum release occurred under conditions known to favor complement fixation by the classical or alternative pathways. Thermal destruction or immune fixation of serum complement before use in culture reduced the magnitude of release to that observed in cultures incubated in the complete absence of serum. Phagocytosis was not essential for release, since cells exposed to particles but treated with a known inhibitor of phagocytosis (cytochalasin B) still showed maximal release in the presence of fresh serum. These data are interpreted to indicate that a heat-labile component of serum, probably a by-product of complement fixation, was primarily responsible for the hydrolase release by AM. On the basis of these findings, individuals suffering from chronic pulmonary disease may suffer acute episodes of lung destruction from endogenous AM enzymes upon the inhalation of materials capable of fixing complement."}
{"id": "PMID:25243", "title": "Evidence for quantitative variability of bacterial opsonic requirements.", "content": "We studied human serum opsonins by using combinations of heat inactivation and chelation to inhibit complement, adsorption to remove antibody, and trypan blue to inactivate the C3 receptor of human polymorphonuclear leukocytes. Streptococcus pneumoniae, serotype 25, required both complement and immunoglobulin for opsonization, even though that strain activated the alternative complement pathway. Both strains of Escherichia coli required antibody and complement, but varied in the degree of dependence on the C3 opsonin, since trypan blue moderately inhibited the killing of E. coli-1 and markedly inhibited the killing of E. coli-2. Serratia marcescens was opsonized in heat-inactivated serum (limited complement) or serum absorbed at 0 degrees C with S. marcescens (limited antibody), but depended on the C3 receptor in absorbed serum. S. marcescens activated the alternative pathway. Thus, opsonic requirements varied with the availability of opsonins. Requirements for bacterial opsonization vary with species and strains within species, perhaps reflecting quantitative relationships among alternative and classical pathway activation of C3, efficiency of adsorption of C3 or immunoglobulin G to bacterial surfaces, and efficiency of attachment of these ligands to polymorphonuclear leukocyte receptors. Furthermore, although not always sufficient for opsonization, the C3 opsonin (activated through either the classical or alternative pathway) appears necessary for effective phagocytosis and killing of all strains studied.", "contents": "Evidence for quantitative variability of bacterial opsonic requirements. We studied human serum opsonins by using combinations of heat inactivation and chelation to inhibit complement, adsorption to remove antibody, and trypan blue to inactivate the C3 receptor of human polymorphonuclear leukocytes. Streptococcus pneumoniae, serotype 25, required both complement and immunoglobulin for opsonization, even though that strain activated the alternative complement pathway. Both strains of Escherichia coli required antibody and complement, but varied in the degree of dependence on the C3 opsonin, since trypan blue moderately inhibited the killing of E. coli-1 and markedly inhibited the killing of E. coli-2. Serratia marcescens was opsonized in heat-inactivated serum (limited complement) or serum absorbed at 0 degrees C with S. marcescens (limited antibody), but depended on the C3 receptor in absorbed serum. S. marcescens activated the alternative pathway. Thus, opsonic requirements varied with the availability of opsonins. Requirements for bacterial opsonization vary with species and strains within species, perhaps reflecting quantitative relationships among alternative and classical pathway activation of C3, efficiency of adsorption of C3 or immunoglobulin G to bacterial surfaces, and efficiency of attachment of these ligands to polymorphonuclear leukocyte receptors. Furthermore, although not always sufficient for opsonization, the C3 opsonin (activated through either the classical or alternative pathway) appears necessary for effective phagocytosis and killing of all strains studied."}
{"id": "PMID:25244", "title": "Interactions between effector cell activity and lymphokines: implications for recovery from herpesvirus infections.", "content": "The destruction of herpesvirus-infected target cells by antibody-dependent and direct cell cytotoxicity was enhanced by the presence of bovine lymphokine-containing preparations. To relate these effects to possible in vivo mechanisms of recovery, several in vitro approaches were used to measure the effects of lymphokine-containing preparations on controlling viral spread. In the first approach it was shown that in the presence of lymphokines, virus-infected cells could be killed earlier in the replication cycle by the mechanism of antibody-dependent cell cytotoxicity, thus possibly limiting spread of virus. That this was indeed the case was demonstrated by a decrease in the area of viral-induced cytopathology as well as in the total number of infected cells present. Secondly, the amount of infectious virus released was also markedly reduced in cultures incubated with lymphokines and immune peripheral blood lymphocytes as compared to cultures treated with either component alone. Finally, lymphokines caused the activation of macrophages. These results are discussed in terms of how various immune parameters may interact in a positive way so as to aid in the recovery from virus infection.", "contents": "Interactions between effector cell activity and lymphokines: implications for recovery from herpesvirus infections. The destruction of herpesvirus-infected target cells by antibody-dependent and direct cell cytotoxicity was enhanced by the presence of bovine lymphokine-containing preparations. To relate these effects to possible in vivo mechanisms of recovery, several in vitro approaches were used to measure the effects of lymphokine-containing preparations on controlling viral spread. In the first approach it was shown that in the presence of lymphokines, virus-infected cells could be killed earlier in the replication cycle by the mechanism of antibody-dependent cell cytotoxicity, thus possibly limiting spread of virus. That this was indeed the case was demonstrated by a decrease in the area of viral-induced cytopathology as well as in the total number of infected cells present. Secondly, the amount of infectious virus released was also markedly reduced in cultures incubated with lymphokines and immune peripheral blood lymphocytes as compared to cultures treated with either component alone. Finally, lymphokines caused the activation of macrophages. These results are discussed in terms of how various immune parameters may interact in a positive way so as to aid in the recovery from virus infection."}
{"id": "PMID:25245", "title": "Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide.", "content": "The 51-residue peptide ovine beta-lipotropin-(41--91) has been synthesized by the solid-phase method in about 5% overall yield. The synthetic product was characterized by partition chromatography on agarose gel, thin-layer chromatography in two solvent systems, paper electrophoresis at two pH values, polyacrylamide gel electrophoresis, amino acid analyses of acid and enzymic hydrolysates, and bioassay for lipolytic and melanotropic activities. The synthetic peptide is about 5.4 times as active on a weight basis as ovine beta-lipotropin in the lipolytic assay. In the melanotropic assay, it was about 2.4 times more active than the beta-lipotropin but only 5% as active as bovine beta-melanotropin. It had negligible opiate activity in the guinea pig ileum assay.", "contents": "Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide. The 51-residue peptide ovine beta-lipotropin-(41--91) has been synthesized by the solid-phase method in about 5% overall yield. The synthetic product was characterized by partition chromatography on agarose gel, thin-layer chromatography in two solvent systems, paper electrophoresis at two pH values, polyacrylamide gel electrophoresis, amino acid analyses of acid and enzymic hydrolysates, and bioassay for lipolytic and melanotropic activities. The synthetic peptide is about 5.4 times as active on a weight basis as ovine beta-lipotropin in the lipolytic assay. In the melanotropic assay, it was about 2.4 times more active than the beta-lipotropin but only 5% as active as bovine beta-melanotropin. It had negligible opiate activity in the guinea pig ileum assay."}
{"id": "PMID:25248", "title": "Glucose oxidation in the chick cornea: effect of diamide on the pentose shunt.", "content": "Chick embryo corneas (stages 38 and 45) have been used to study variations in pentose shunt activity following the use of a glutathione-specific oxidizing agent, diamide, and a sulfydryl blocking agent, N-ethylmaleimide (NEM). Shunt activity was measured by the ratio of radiolabeled carbon 1 (14C-1) of glucose to radiolabeled carbon 6 (14C-6) of glucose derived as expired 14CO2. Diamide and NEM were both found to increase pentose shunt activity relative to glycolysis, although by different means. Diamide appeared to exert its effect by oxidizing glutathione and creating a demand for higher shunt activity to facilitate glutathione reduction by NADPH. Both C-1 and C-6 oxidation were increased, but C-1 oxidation was increased to a much greater extent. In contrast, NEM decreased both C-1 and C-6 oxidation, with C-6 preferentially affected. Thus NEM appears to preferentially inhibit the enzymatic machinery of the glycolytic-tricarboxylic acid cycle pathway and acts as an effective metabolic stress on the cornea. Our data suggest that the pentose shunt in the cornea may serve as an important alternative pathway under conditions of metabolic stress for glucose utilization and the production of energy (ATP) in the corneal cells.", "contents": "Glucose oxidation in the chick cornea: effect of diamide on the pentose shunt. Chick embryo corneas (stages 38 and 45) have been used to study variations in pentose shunt activity following the use of a glutathione-specific oxidizing agent, diamide, and a sulfydryl blocking agent, N-ethylmaleimide (NEM). Shunt activity was measured by the ratio of radiolabeled carbon 1 (14C-1) of glucose to radiolabeled carbon 6 (14C-6) of glucose derived as expired 14CO2. Diamide and NEM were both found to increase pentose shunt activity relative to glycolysis, although by different means. Diamide appeared to exert its effect by oxidizing glutathione and creating a demand for higher shunt activity to facilitate glutathione reduction by NADPH. Both C-1 and C-6 oxidation were increased, but C-1 oxidation was increased to a much greater extent. In contrast, NEM decreased both C-1 and C-6 oxidation, with C-6 preferentially affected. Thus NEM appears to preferentially inhibit the enzymatic machinery of the glycolytic-tricarboxylic acid cycle pathway and acts as an effective metabolic stress on the cornea. Our data suggest that the pentose shunt in the cornea may serve as an important alternative pathway under conditions of metabolic stress for glucose utilization and the production of energy (ATP) in the corneal cells."}
{"id": "PMID:25256", "title": "Blood gas changes during panting in a small East African antelope, the dik-dik.", "content": "Five adult male dik-dik (Madoqua kirkii) were exposed in a climatic chamber to an air temperature of 45 degrees C. Measurements were made of rectal temperature (Tre) and respiratory frequency (f) and arterial blood samples taken before and during heat exposure were analyzed for pH, PCO2 and PO2. During exposure, Tre and f increased in all animals. In the first 80 min dik-dik displayed thermal tachypnea and minor changes in blood gases. Continued exposure lead to hyperpnea accompanied by a fall in PaCO2 and a rise in pH. PaCO2 at first fell and then increased toward or above control levels. The dik-dik did not display second phase breathing. This observation confirms that second phase breathing is not essential to the development of respiratory alkalosis. The main conclusion of the study is that the dik-dik, unlike another heat-adapted antelope, the wildebeest (Taylor, Robertshaw, and Hoffmann. Am. J. Physiol. 217:907-910, 1969), is unable to resist alkalosis during heat stress.", "contents": "Blood gas changes during panting in a small East African antelope, the dik-dik. Five adult male dik-dik (Madoqua kirkii) were exposed in a climatic chamber to an air temperature of 45 degrees C. Measurements were made of rectal temperature (Tre) and respiratory frequency (f) and arterial blood samples taken before and during heat exposure were analyzed for pH, PCO2 and PO2. During exposure, Tre and f increased in all animals. In the first 80 min dik-dik displayed thermal tachypnea and minor changes in blood gases. Continued exposure lead to hyperpnea accompanied by a fall in PaCO2 and a rise in pH. PaCO2 at first fell and then increased toward or above control levels. The dik-dik did not display second phase breathing. This observation confirms that second phase breathing is not essential to the development of respiratory alkalosis. The main conclusion of the study is that the dik-dik, unlike another heat-adapted antelope, the wildebeest (Taylor, Robertshaw, and Hoffmann. Am. J. Physiol. 217:907-910, 1969), is unable to resist alkalosis during heat stress."}
{"id": "PMID:25260", "title": "Alpha-l-arabinofuranosidase from Rhodotorula flava.", "content": "An alpha-L-arabinofuranosidase (EC 3.2.1.55) from the culture fluid of Rhodotorula flava IFO 0407 grown on beet arabinan as a carbon source has been highly purified. The purified enzyme has a pH optimum of 2.0. The enzyme is unusually acid stable, retaining 82% of its activity after being maintained for 24 h at pH 1.5 and at 30 degrees C. The apparent Km and Vmax values of the enzyme for phenyl alpha-L-arabinofuranoside were determined to be 9.1 mM and 72.5 mumol per min per mg of protein, respectively.", "contents": "Alpha-l-arabinofuranosidase from Rhodotorula flava. An alpha-L-arabinofuranosidase (EC 3.2.1.55) from the culture fluid of Rhodotorula flava IFO 0407 grown on beet arabinan as a carbon source has been highly purified. The purified enzyme has a pH optimum of 2.0. The enzyme is unusually acid stable, retaining 82% of its activity after being maintained for 24 h at pH 1.5 and at 30 degrees C. The apparent Km and Vmax values of the enzyme for phenyl alpha-L-arabinofuranoside were determined to be 9.1 mM and 72.5 mumol per min per mg of protein, respectively."}
{"id": "PMID:25261", "title": "Protonmotive force and motility of Bacillus subtilis.", "content": "Motility of Bacillus subtilis was inhibited within a few minutes by a combination of valinomycin and a high concentration of potassium ions in the medium at neutral pH. Motility was restored by lowering the concentration of valinomycin or potassium ions. The valinomycin concentration necessary for motility inhibition was determined at various concentrations of potassium ions and various pH's. At pH 7.5, valinomycin of any concentration did not inhibit the motility, when the potassium ion concentration was lower than 9 mM. In the presence of 230 mM potassium ion, the motility inhibition by valinomycin was not detected at pH lower than 6.1. These results are easily explained by the idea that the motility of B. subtilis is supported by the electrochemical potential difference of the proton across the membrane, or the protonmotive force. The electrochemical potential difference necessary for motility was estimated to be about -90 mV.", "contents": "Protonmotive force and motility of Bacillus subtilis. Motility of Bacillus subtilis was inhibited within a few minutes by a combination of valinomycin and a high concentration of potassium ions in the medium at neutral pH. Motility was restored by lowering the concentration of valinomycin or potassium ions. The valinomycin concentration necessary for motility inhibition was determined at various concentrations of potassium ions and various pH's. At pH 7.5, valinomycin of any concentration did not inhibit the motility, when the potassium ion concentration was lower than 9 mM. In the presence of 230 mM potassium ion, the motility inhibition by valinomycin was not detected at pH lower than 6.1. These results are easily explained by the idea that the motility of B. subtilis is supported by the electrochemical potential difference of the proton across the membrane, or the protonmotive force. The electrochemical potential difference necessary for motility was estimated to be about -90 mV."}
{"id": "PMID:25262", "title": "Fate of heterospecific transforming DNA bound to Streptococcus sanguis.", "content": "The fate of 3H-labeled str-r fus-s DNA from Streptococcus pneumoniae, bound after a 1-min uptake to 14C-labeled str-s fus-r S. sanguis recipients, was followed by techniques previously developed for analyzing the fate of homospecific DNA. Heterospecific S. pneumoniae DNA was bound and formed complexes with recipient protein in a manner similar to that of homospecific DNA but transformed relatively poorly. The rate at which complexed heterospecific DNA becomes physically associated with recipient DNA, and at which donor markers are integrated into the chromosome, was slower than in the case of homospecific DNA. In addition, about half of the heterospecific donor counts initially bound in trichloracetic acid-insoluble form were gradually solubilized and released from the cell. The association of heterospecific DNA with the recipient chromosome was more unstable than that involving homospecific DNA, since only associations of the former type were largely dissociated by isolation and resedimentation. The donor DNA-containing material so dissociated had the same sedimentation properties as complexed heterospecific DNA before association, indicating that the complex of single-stranded donor DNA and recipient protein formed on uptake moves as a whole from its site of formation to synapse with the chromosome.", "contents": "Fate of heterospecific transforming DNA bound to Streptococcus sanguis. The fate of 3H-labeled str-r fus-s DNA from Streptococcus pneumoniae, bound after a 1-min uptake to 14C-labeled str-s fus-r S. sanguis recipients, was followed by techniques previously developed for analyzing the fate of homospecific DNA. Heterospecific S. pneumoniae DNA was bound and formed complexes with recipient protein in a manner similar to that of homospecific DNA but transformed relatively poorly. The rate at which complexed heterospecific DNA becomes physically associated with recipient DNA, and at which donor markers are integrated into the chromosome, was slower than in the case of homospecific DNA. In addition, about half of the heterospecific donor counts initially bound in trichloracetic acid-insoluble form were gradually solubilized and released from the cell. The association of heterospecific DNA with the recipient chromosome was more unstable than that involving homospecific DNA, since only associations of the former type were largely dissociated by isolation and resedimentation. The donor DNA-containing material so dissociated had the same sedimentation properties as complexed heterospecific DNA before association, indicating that the complex of single-stranded donor DNA and recipient protein formed on uptake moves as a whole from its site of formation to synapse with the chromosome."}
{"id": "PMID:25263", "title": "Cell-free biosynthesis of the O-acetylated N-acetylneuraminic acid capsular polysaccharide of group C meningococci.", "content": "A cell-free system was established to study the biosynthesis of group C meningococcal capsular polysaccharide, an alpha-2 leads to 9-linked N-acetylneuraminic acid (NeuAc) homopolymer containing O-acetyl groups at either C7 or C8. Sialyltransferase activity, isolated from group C meningococcus strain C-11, catalyzed incorporation of [14C]NeuAc from CMP (CMP--[14C]NeuAc) into polymeric form. This sialyltransferase was stimulated by addition of meningococcus group C and Escherichia coli K92 capsular polysaccharides, the latter being an alpha-2 leads to 8- and alpha-2 leads to 9-linked NeuAc heteropolymer. Group C meningococcal sialyltransferase did not require divalent ions but was stimulated by Mn2+. Attempts to demonstrate a lipid-soluble intermediate in the biosynthesis of this NeuAc polymer were unsuccessful. Meningococcal group C sialyltransferase incorporated NeuAc into a membrane-associated product. The polysaccharide can be extracted from the membrane-bound fraction with Triton X-100. The newly synthesized polysaccharide coprecipitates with authentic group C antigen in meningococcal group C antiserum and is degraded by sodium metaperiodate, indicating that the NeuAc polymer synthesized by the cell-free system consists of alpha-2 leads to 9 linkage. Meningococcal group C spheroplast membranes contain an O-acetylase that can catalyze the transfer of acetyl groups from acetyl coenzyme A to the in vitro-synthesized polysaccharide.", "contents": "Cell-free biosynthesis of the O-acetylated N-acetylneuraminic acid capsular polysaccharide of group C meningococci. A cell-free system was established to study the biosynthesis of group C meningococcal capsular polysaccharide, an alpha-2 leads to 9-linked N-acetylneuraminic acid (NeuAc) homopolymer containing O-acetyl groups at either C7 or C8. Sialyltransferase activity, isolated from group C meningococcus strain C-11, catalyzed incorporation of [14C]NeuAc from CMP (CMP--[14C]NeuAc) into polymeric form. This sialyltransferase was stimulated by addition of meningococcus group C and Escherichia coli K92 capsular polysaccharides, the latter being an alpha-2 leads to 8- and alpha-2 leads to 9-linked NeuAc heteropolymer. Group C meningococcal sialyltransferase did not require divalent ions but was stimulated by Mn2+. Attempts to demonstrate a lipid-soluble intermediate in the biosynthesis of this NeuAc polymer were unsuccessful. Meningococcal group C sialyltransferase incorporated NeuAc into a membrane-associated product. The polysaccharide can be extracted from the membrane-bound fraction with Triton X-100. The newly synthesized polysaccharide coprecipitates with authentic group C antigen in meningococcal group C antiserum and is degraded by sodium metaperiodate, indicating that the NeuAc polymer synthesized by the cell-free system consists of alpha-2 leads to 9 linkage. Meningococcal group C spheroplast membranes contain an O-acetylase that can catalyze the transfer of acetyl groups from acetyl coenzyme A to the in vitro-synthesized polysaccharide."}
{"id": "PMID:25264", "title": "Involvement of the product of the glnF gene in the autogenous regulation of glutamine synthetase formation in Klebsiella aerogenes.", "content": "Mutations in a site, glnF, linked by P1-mediated transduction of argG on the chromosome of Klebsiella aerogenes, result in a requirement for glutamine. Mutants in this gene have in all media a level of glutamine synthetase (GS) corresponding to the level found in the wild-type strain grown in the medium producing the strongest repression of GS. The adenylylation and deadenylylation of GS in glnF mutants is normal. The glutamine requirement of glnF mutants could be suppressed by mutations in the structural gene for GS, glnA. These mutations result in altered regulation of GS synthesis, regardless of the presence or absence of the glnF mutation (GlnR phenotype). In GlnR mutants the GS level is higher than in the wild-type strain when the cells are cultured in strongly repressing medium, but lower than in the wild-type strain when cells are cultured in a derepressing medium. Heterozygous merodiploids carrying a normal glnA gene as well as a glnA gene responsible for the GlnR phenotype behave in every respect like merodiploids carrying two normal glnA genes. These results confirm autogenous regulation of GS synthesis and indicate that GS is both a repressor and an activator of GS synthesis. The mutation in glnA responsible for the GLnR phenotype has apparently resulted in the formation of a GS that is incompetent both as repressor and as activator of GS synthesis. According to this hypothesis, the product of the glnF gene is necessary for activation of the glnA gene by GS.", "contents": "Involvement of the product of the glnF gene in the autogenous regulation of glutamine synthetase formation in Klebsiella aerogenes. Mutations in a site, glnF, linked by P1-mediated transduction of argG on the chromosome of Klebsiella aerogenes, result in a requirement for glutamine. Mutants in this gene have in all media a level of glutamine synthetase (GS) corresponding to the level found in the wild-type strain grown in the medium producing the strongest repression of GS. The adenylylation and deadenylylation of GS in glnF mutants is normal. The glutamine requirement of glnF mutants could be suppressed by mutations in the structural gene for GS, glnA. These mutations result in altered regulation of GS synthesis, regardless of the presence or absence of the glnF mutation (GlnR phenotype). In GlnR mutants the GS level is higher than in the wild-type strain when the cells are cultured in strongly repressing medium, but lower than in the wild-type strain when cells are cultured in a derepressing medium. Heterozygous merodiploids carrying a normal glnA gene as well as a glnA gene responsible for the GlnR phenotype behave in every respect like merodiploids carrying two normal glnA genes. These results confirm autogenous regulation of GS synthesis and indicate that GS is both a repressor and an activator of GS synthesis. The mutation in glnA responsible for the GLnR phenotype has apparently resulted in the formation of a GS that is incompetent both as repressor and as activator of GS synthesis. According to this hypothesis, the product of the glnF gene is necessary for activation of the glnA gene by GS."}
{"id": "PMID:25265", "title": "Glycerolipid biosynthesis in Saccharomyces cerevisiae: sn-glycerol-3-phosphate and dihydroxyacetone phosphate acyltransferase activities.", "content": "Yeast acyl-coenzyme A:dihydroxyacetone-phosphate O-acyltransferase (DHAP acyltransferase; EC 2.3.1.42) was investigated to (i) determine whether its activity and that of acyl-coenzyme A:sn-glycerol-3-phosphate O-acyltransferase (glycerol-P acyltransferase; EC 2.3.1.15) represent dual catalytic functions of a single membranous enzyme, (ii) estimate the relative contributions of the glycerol-P and DHAP pathways for yeast glycerolipid synthesis, and (iii) evaluate the suitability of yeast for future genetic investigations of the eucaryotic glycerol-P and DHAP acyltransferase activities. The membranous DHAP acyltransferase activity showed an apparent Km of 0.79 mM for DHAP, with a Vmax of 5.3 nmol/min per mg, whereas the glycerol-P acyltransferase activity showed an apparent Km of 0.05 mM for glycerol-P, with a Vmax of 3.4 nmol/min per mg. Glycerol-P was a competitive inhibitor (Ki, 0.07 mM) of the DHAP acyltransferase activity, and DHAP was a competitive inhibitor (Ki, 0.91 mM) of the glycerol-P acyltransferase activity. The two acyltransferase activities exhibited marked similarities in their pH dependence, acyl-coenzyme A chain length preference and substrate concentration dependencies, thermolability, and patterns of inactivation by N-ethylmaleimide, trypsin, and detergents. Thus, the data strongly suggest that yeast glycerol-P and DHAP acyltransferase activities represent dual catalytic functions of a single membrane-bound enzyme. Furthermore, since no acyl-DHAP oxidoreductase activity could be detected in yeast membranes, the DHAP pathway for glycerolipid synthesis may not operate in yeast.", "contents": "Glycerolipid biosynthesis in Saccharomyces cerevisiae: sn-glycerol-3-phosphate and dihydroxyacetone phosphate acyltransferase activities. Yeast acyl-coenzyme A:dihydroxyacetone-phosphate O-acyltransferase (DHAP acyltransferase; EC 2.3.1.42) was investigated to (i) determine whether its activity and that of acyl-coenzyme A:sn-glycerol-3-phosphate O-acyltransferase (glycerol-P acyltransferase; EC 2.3.1.15) represent dual catalytic functions of a single membranous enzyme, (ii) estimate the relative contributions of the glycerol-P and DHAP pathways for yeast glycerolipid synthesis, and (iii) evaluate the suitability of yeast for future genetic investigations of the eucaryotic glycerol-P and DHAP acyltransferase activities. The membranous DHAP acyltransferase activity showed an apparent Km of 0.79 mM for DHAP, with a Vmax of 5.3 nmol/min per mg, whereas the glycerol-P acyltransferase activity showed an apparent Km of 0.05 mM for glycerol-P, with a Vmax of 3.4 nmol/min per mg. Glycerol-P was a competitive inhibitor (Ki, 0.07 mM) of the DHAP acyltransferase activity, and DHAP was a competitive inhibitor (Ki, 0.91 mM) of the glycerol-P acyltransferase activity. The two acyltransferase activities exhibited marked similarities in their pH dependence, acyl-coenzyme A chain length preference and substrate concentration dependencies, thermolability, and patterns of inactivation by N-ethylmaleimide, trypsin, and detergents. Thus, the data strongly suggest that yeast glycerol-P and DHAP acyltransferase activities represent dual catalytic functions of a single membrane-bound enzyme. Furthermore, since no acyl-DHAP oxidoreductase activity could be detected in yeast membranes, the DHAP pathway for glycerolipid synthesis may not operate in yeast."}
{"id": "PMID:25266", "title": "Intracellular serine protease of Bacillus subtilis: sequence homology with extracellular subtilisins.", "content": "Intracellular serine protease was isolated from stationary-grown Bacillus subtilis A-50 cells and purified to homogeneity. The molecular weight of the enzyme is 31,000 +/- 1,000, with an isoelectric point of 4.3. Its amino acid composition is characteristically enriched in glutamic acid content, differing from that of extra-cellular subtilisins. The enzyme is completely inhibited with phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Intracellular protease possesses negligible activity towards bovine serum albumin and hemoglobin, but has 5- to 20-fold higher specific activity against p-nitroanilides of benzyloxycarbonyl tripeptides than subtilisin BPN'. Esterolytic activity of the enzyme is also higher than that of subtilisin BPN'. The enzyme is sequence homologous with secretory subtilisins throughout 50 determined NH2-terminal residues, indicating the presence of duplicated structural genes for serine proteases in the B. subtilis genome. The occurrence of two homologous genes in the cell might accelerate the evolution of serine protease not only by the loosening of selective constrainst, but also by creation of sequence variants by means of intragenic recombination. Three molecular forms of intracellular protease were found, two of them with NH2-terminal glutamic acid and one minor form, three residues longer, with asparagine as NH2 terminus. These data indicate the possible presence of an enzyme precursor proteolytically modified during cell growth.", "contents": "Intracellular serine protease of Bacillus subtilis: sequence homology with extracellular subtilisins. Intracellular serine protease was isolated from stationary-grown Bacillus subtilis A-50 cells and purified to homogeneity. The molecular weight of the enzyme is 31,000 +/- 1,000, with an isoelectric point of 4.3. Its amino acid composition is characteristically enriched in glutamic acid content, differing from that of extra-cellular subtilisins. The enzyme is completely inhibited with phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Intracellular protease possesses negligible activity towards bovine serum albumin and hemoglobin, but has 5- to 20-fold higher specific activity against p-nitroanilides of benzyloxycarbonyl tripeptides than subtilisin BPN'. Esterolytic activity of the enzyme is also higher than that of subtilisin BPN'. The enzyme is sequence homologous with secretory subtilisins throughout 50 determined NH2-terminal residues, indicating the presence of duplicated structural genes for serine proteases in the B. subtilis genome. The occurrence of two homologous genes in the cell might accelerate the evolution of serine protease not only by the loosening of selective constrainst, but also by creation of sequence variants by means of intragenic recombination. Three molecular forms of intracellular protease were found, two of them with NH2-terminal glutamic acid and one minor form, three residues longer, with asparagine as NH2 terminus. These data indicate the possible presence of an enzyme precursor proteolytically modified during cell growth."}
{"id": "PMID:25267", "title": "Acid proteases. II. Fluorescence study of the interaction of Cladosporium acid protease with glycyl-DL-norleucine methyl ester in the presence of cupric ions.", "content": "Glycyl-DL-norleucine methyl ester (GN), a diazoacetyl-DL-norleucine methyl ester (DAN) analog, in the presence of cupric ions was found to partially quench the protein fluorescence of acid protease from Cladosporium sp. No. 45-2, and cupric ions were also found to quench the fluorescence. These quenchings were pH-dependent. GN alone did not quench the fluorescence of the enzyme. The interaction between the enzyme and GN in the presence of cupric ions was studied statically at pH 5.4 in terms of fluorescence change. The dissociation constant, Kd, of the enzyme-GN complex in the presence of a 20-fold molar excess of cupric ions (0.08 mM) determined by fluorescence titration at 30 degrees C (Kd = 1.86 mM) was in good agreement with that obtained for GN from kinetics of inhibition of DAN-induced inactivation in the presence of a 20-fold molar excess of cupric ions at 30 degrees C (KA = 1.94 mM) (Kanazawa, H. (1977) J. Biochem. 81, 1739-1744). At various concentrations of cupric ions, no change of Kd was found. These results suggest that cupric ions are attracted to a negatively charged carboxyl group responsible for the formation of the enzyme-GN complex.", "contents": "Acid proteases. II. Fluorescence study of the interaction of Cladosporium acid protease with glycyl-DL-norleucine methyl ester in the presence of cupric ions. Glycyl-DL-norleucine methyl ester (GN), a diazoacetyl-DL-norleucine methyl ester (DAN) analog, in the presence of cupric ions was found to partially quench the protein fluorescence of acid protease from Cladosporium sp. No. 45-2, and cupric ions were also found to quench the fluorescence. These quenchings were pH-dependent. GN alone did not quench the fluorescence of the enzyme. The interaction between the enzyme and GN in the presence of cupric ions was studied statically at pH 5.4 in terms of fluorescence change. The dissociation constant, Kd, of the enzyme-GN complex in the presence of a 20-fold molar excess of cupric ions (0.08 mM) determined by fluorescence titration at 30 degrees C (Kd = 1.86 mM) was in good agreement with that obtained for GN from kinetics of inhibition of DAN-induced inactivation in the presence of a 20-fold molar excess of cupric ions at 30 degrees C (KA = 1.94 mM) (Kanazawa, H. (1977) J. Biochem. 81, 1739-1744). At various concentrations of cupric ions, no change of Kd was found. These results suggest that cupric ions are attracted to a negatively charged carboxyl group responsible for the formation of the enzyme-GN complex."}
{"id": "PMID:25268", "title": "Purification and some properties of a neutral muscle pyrophosphatase.", "content": "In the water-soluble fraction of rabbit skeletal muscle, at least two types of inorganic pyro phosphatase (PPase) are distinguishable on ion exchange column chromatography. One of them, pyrophosphatase-A (PPase-A), was isolated in an electrophoretically homogeneous form. This enzyme catalyzed the hydrolysis of PPi but not that of other phosphate esters. Only Mg2+ was required for activity and stability. Other cations such as Ca2+, Co2+, Mn2+, and Zn2+ had no activating effect. The activity of this PPase was optimum at pH 7.4. ATP, ADP, sodium imidodiphosphate (PNP), p-chloromercuribenzoate, and Ca2+ inhibited its enzymic activity. The enzyme was protected by dithiothreitol (DTT) against heat denaturation. The molecular weight was estimated to be 67,000 by gel filtration and the molecular size of the subunit was found to be 35,000 by gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). The enzyme probably consists of two identical subunits of 35,000 daltons.", "contents": "Purification and some properties of a neutral muscle pyrophosphatase. In the water-soluble fraction of rabbit skeletal muscle, at least two types of inorganic pyro phosphatase (PPase) are distinguishable on ion exchange column chromatography. One of them, pyrophosphatase-A (PPase-A), was isolated in an electrophoretically homogeneous form. This enzyme catalyzed the hydrolysis of PPi but not that of other phosphate esters. Only Mg2+ was required for activity and stability. Other cations such as Ca2+, Co2+, Mn2+, and Zn2+ had no activating effect. The activity of this PPase was optimum at pH 7.4. ATP, ADP, sodium imidodiphosphate (PNP), p-chloromercuribenzoate, and Ca2+ inhibited its enzymic activity. The enzyme was protected by dithiothreitol (DTT) against heat denaturation. The molecular weight was estimated to be 67,000 by gel filtration and the molecular size of the subunit was found to be 35,000 by gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). The enzyme probably consists of two identical subunits of 35,000 daltons."}
{"id": "PMID:25269", "title": "Bacteriolytic enzyme induced from pyocinogenic Pseudomonas aeruginosa. Purification and characterization of PR1-lysozyme.", "content": "A bacteriolytic enzyme, PR1-lysozyme, has been purified from the lysate of mitomycin C-induced pyocinogenic Pseudomonas aeruginosa, by acrinol treatment, Amberlite CG-50 chromatography, ammonium sulfate fractionation, Sephadex G-100 gel filtration and two cycles of SP-Sephadex C-50 chromatography. Homogeneity of the preparation was demonstrated by three electrophoretic techniques. PR1-lysozyme is a basic protein (pI, 9.4) and consists of a single polypeptide chain having a molecular weight of 24,000. The amino acid composition of the protein was analyzed, and no cystein residue was found among more than 210 amino acid residues. The optimum pH for enzymatic activity was 6.4 and the enzyme exhibited about 50 to 70 times greater specific activity than hen egg-white lysozyme when assayed with chloroform-killed P. aeruginosa as a substrate. By analyzing the products of enzymatic action on purified peptidoglycan of P. aeruginosa, the enzyme was identified as an N-acetylmuramidase, i.e., the same classification as hen-egg-white lysozyme. PR1-lysozyme did not show any activity towards intact cells of gram-positive and gram-negative bacteria tested. However, the enzyme was able to lyse chloroform-killed gram-negative and gram-positive bacteria.", "contents": "Bacteriolytic enzyme induced from pyocinogenic Pseudomonas aeruginosa. Purification and characterization of PR1-lysozyme. A bacteriolytic enzyme, PR1-lysozyme, has been purified from the lysate of mitomycin C-induced pyocinogenic Pseudomonas aeruginosa, by acrinol treatment, Amberlite CG-50 chromatography, ammonium sulfate fractionation, Sephadex G-100 gel filtration and two cycles of SP-Sephadex C-50 chromatography. Homogeneity of the preparation was demonstrated by three electrophoretic techniques. PR1-lysozyme is a basic protein (pI, 9.4) and consists of a single polypeptide chain having a molecular weight of 24,000. The amino acid composition of the protein was analyzed, and no cystein residue was found among more than 210 amino acid residues. The optimum pH for enzymatic activity was 6.4 and the enzyme exhibited about 50 to 70 times greater specific activity than hen egg-white lysozyme when assayed with chloroform-killed P. aeruginosa as a substrate. By analyzing the products of enzymatic action on purified peptidoglycan of P. aeruginosa, the enzyme was identified as an N-acetylmuramidase, i.e., the same classification as hen-egg-white lysozyme. PR1-lysozyme did not show any activity towards intact cells of gram-positive and gram-negative bacteria tested. However, the enzyme was able to lyse chloroform-killed gram-negative and gram-positive bacteria."}
{"id": "PMID:25270", "title": "Studies on soybean trypsin inhibitors. XIII. Preparation and characterization of active fragments from Bowman-Birk proteinase inhibitor.", "content": "Soybean Bowman-Birk inhibitor, a double-headed inhibitor of trypsin and alpha-chymotrypsin, was treated with cyanogen bromide and then pepsin to yield two inhibitory active fragments. Structural investigation showed that one of the fragments was derived from the trypsin inhibitory domain and the other from the chymotrypsin inhibitory domain of the inhibitor. In contrast to the unusual stability of the native inhibitor, the separated domains were less stable and could be inactivated with excess proteinases. These results suggest that the legume double-headed inhibitors acquired their unusual stability by duplicating an ancestral single-headed structure.", "contents": "Studies on soybean trypsin inhibitors. XIII. Preparation and characterization of active fragments from Bowman-Birk proteinase inhibitor. Soybean Bowman-Birk inhibitor, a double-headed inhibitor of trypsin and alpha-chymotrypsin, was treated with cyanogen bromide and then pepsin to yield two inhibitory active fragments. Structural investigation showed that one of the fragments was derived from the trypsin inhibitory domain and the other from the chymotrypsin inhibitory domain of the inhibitor. In contrast to the unusual stability of the native inhibitor, the separated domains were less stable and could be inactivated with excess proteinases. These results suggest that the legume double-headed inhibitors acquired their unusual stability by duplicating an ancestral single-headed structure."}
{"id": "PMID:25271", "title": "A new affinity adsorbent for guanyloribonuclease. Guanylyl-(2'-5')-guanosine coupled to aminohexyl-Sepharose.", "content": "Guanylyl-(2'-5')-guanosine binds to RNase T1 in 1:1 stoichiometry with a dissociation constant of 0.22 mM at pH 5.0 and 25 degrees C. This nucleotide, coupled to aminohexyl-Sepharose 4B, is able to serve as an affinity adsorbent for guanyloribonuclease [EC 3.1.4.8]. The strength of interaction between the adsorbent and various guanyloribonucleases at pH 5.0 was found to decrease in the following order: RNase N1 greater than RNase F1 greater than RNase T1 greater than RNase St. The bound enzymes can be released from the adsorbent either by increase of ionic strength or by increasing the pH from 5.0 to 7.5. The interaction between RNase T1 and the adsorbent is weakened by the presence of a low concentration of 2', 3'-, or 5'-GMP, which are competitive inhibitors of the enzyme. RNase F1 was purified to homogeneity by use of this affinity adsorbent.", "contents": "A new affinity adsorbent for guanyloribonuclease. Guanylyl-(2'-5')-guanosine coupled to aminohexyl-Sepharose. Guanylyl-(2'-5')-guanosine binds to RNase T1 in 1:1 stoichiometry with a dissociation constant of 0.22 mM at pH 5.0 and 25 degrees C. This nucleotide, coupled to aminohexyl-Sepharose 4B, is able to serve as an affinity adsorbent for guanyloribonuclease [EC 3.1.4.8]. The strength of interaction between the adsorbent and various guanyloribonucleases at pH 5.0 was found to decrease in the following order: RNase N1 greater than RNase F1 greater than RNase T1 greater than RNase St. The bound enzymes can be released from the adsorbent either by increase of ionic strength or by increasing the pH from 5.0 to 7.5. The interaction between RNase T1 and the adsorbent is weakened by the presence of a low concentration of 2', 3'-, or 5'-GMP, which are competitive inhibitors of the enzyme. RNase F1 was purified to homogeneity by use of this affinity adsorbent."}
{"id": "PMID:25274", "title": "Purification and characterization of lysozyme produced by Streptomyces erythraeus.", "content": "A species of lysozyme (SE lysozyme) was purified from culture filtrate of Streptomyces erythraeus. The enzyme has a molecular weight of 18,500 as determined by ultracentrifugation. Its isoelectric point is 9.5, and it shows optimal activity at pH 4.0 with an optimal ionic strength of 0.1. Investigation of the substrate specificity showed SE lysozyme to be an N-acetyl-muramidase. The simplest product in the digest of cell walls of Micrococcus lysodeikticus was identified as a disaccharide, [GlcNAcbeta(1 leads to 4) MurNAc]. While S. aureus as well as M. lysodeikticus was lysed by this lysozyme, chitin and its derivatives were not.", "contents": "Purification and characterization of lysozyme produced by Streptomyces erythraeus. A species of lysozyme (SE lysozyme) was purified from culture filtrate of Streptomyces erythraeus. The enzyme has a molecular weight of 18,500 as determined by ultracentrifugation. Its isoelectric point is 9.5, and it shows optimal activity at pH 4.0 with an optimal ionic strength of 0.1. Investigation of the substrate specificity showed SE lysozyme to be an N-acetyl-muramidase. The simplest product in the digest of cell walls of Micrococcus lysodeikticus was identified as a disaccharide, [GlcNAcbeta(1 leads to 4) MurNAc]. While S. aureus as well as M. lysodeikticus was lysed by this lysozyme, chitin and its derivatives were not."}
{"id": "PMID:25275", "title": "Induction of hepatic tyrosine aminotransferase mRNA by protein synthesis inhibitors.", "content": "Several protein synthesis inhibitors were as effective as the inducers hydrocortisone or cyclic AMP in elevating rat liver tyrosine aminotransferase mRNA levels when assayed in the wheat germ cell-free translational system. Cycloheximide, emetine, or puromycin increased this mRNA activity 6- to 7-fold within 4 h after in vivo administration. No increase in total hepatic mRNA levels or tryptophan oxygenase mRNA was found after treatment with these protein synthesis inhibitors. Furthermesults suggest that a short lived protein may specifically regulate the level of functional hepatic tyrosine aminotransferase mRNA or that ongoing translation of this mRNA is required for its degradation.", "contents": "Induction of hepatic tyrosine aminotransferase mRNA by protein synthesis inhibitors. Several protein synthesis inhibitors were as effective as the inducers hydrocortisone or cyclic AMP in elevating rat liver tyrosine aminotransferase mRNA levels when assayed in the wheat germ cell-free translational system. Cycloheximide, emetine, or puromycin increased this mRNA activity 6- to 7-fold within 4 h after in vivo administration. No increase in total hepatic mRNA levels or tryptophan oxygenase mRNA was found after treatment with these protein synthesis inhibitors. Furthermesults suggest that a short lived protein may specifically regulate the level of functional hepatic tyrosine aminotransferase mRNA or that ongoing translation of this mRNA is required for its degradation."}
{"id": "PMID:25282", "title": "The role of Ca2+ on pH-induced hydrodynamic changes of bovine pancreatic deoxyribonuclease A.", "content": "DNase A studied by gel filtration on Sephadex G-100 at pH 7.4 in 40 mM Tris-HCl buffer, behaves hydrodynamically as a spherical monomeric macromolecule of around 31,000 molecular weight, with a Stokes radius = 24.7 A, f/fo = 1.19, and D20,W = 8.69. Similar results were obtained by analytical dialysis using zinc chloride-modified cellophane membranes. The elution volume of DNase A decreases as the pH increases between pH 4.7 and pH 9.5. This effect has been attributed to a change in the tridimensional structure of the protein and interpreted as a modification in the axial ratio due to unfolding of the polypeptide chain with increase in the apparent Stokes radius. The addition of Ca2+ produce reversion of the pH-induced changes at pH 9.5. The transition occurs when Ca2+ binds to at least two binding sites (n = 1.66 in a Hill plot) with a Kd = 8.9 X 10(-5) M and the effect appears to be cooperative. These findings support the hypothesis that Ca2+-binding to DNase A causes a conformational change that maintains a more active structure of the enzyme, especially when the pH-induced unfolding reduces its activity.", "contents": "The role of Ca2+ on pH-induced hydrodynamic changes of bovine pancreatic deoxyribonuclease A. DNase A studied by gel filtration on Sephadex G-100 at pH 7.4 in 40 mM Tris-HCl buffer, behaves hydrodynamically as a spherical monomeric macromolecule of around 31,000 molecular weight, with a Stokes radius = 24.7 A, f/fo = 1.19, and D20,W = 8.69. Similar results were obtained by analytical dialysis using zinc chloride-modified cellophane membranes. The elution volume of DNase A decreases as the pH increases between pH 4.7 and pH 9.5. This effect has been attributed to a change in the tridimensional structure of the protein and interpreted as a modification in the axial ratio due to unfolding of the polypeptide chain with increase in the apparent Stokes radius. The addition of Ca2+ produce reversion of the pH-induced changes at pH 9.5. The transition occurs when Ca2+ binds to at least two binding sites (n = 1.66 in a Hill plot) with a Kd = 8.9 X 10(-5) M and the effect appears to be cooperative. These findings support the hypothesis that Ca2+-binding to DNase A causes a conformational change that maintains a more active structure of the enzyme, especially when the pH-induced unfolding reduces its activity."}
{"id": "PMID:25283", "title": "Energy transduction in the photosynthetic membranes of the cyanobacterium (blue-green alga) P-lectonema boryanum.", "content": "Membrane preparations isolated from the photosynthetic lamellae of the cyanobacterium Plectonema boryanum generate upon illumination  a transmembrane pH gradient of approximately 2 to 3 pH units (acid inside), as determined from the distribution of either fluorescent or radioactive amines (9 aminoacridine and [14C]methylamine, respectively). Using the distribution of permeant ions to measure the electrical potential across the membrane, it was found that the latter is practically nil under conditions in which the deltapH is formed and photophosphorylation takes place. In agreement with the above findings cyclic photophosphorylation in this membrane preparation is inhibited by agents shown to collapse the deltapH but not by agents which should collapse the electrical potential. It is deduced that the pattern of proton movement in the photosynthetic lamellae of intact Plectonema spheroplasts corresponds to that of the cell-free membrane system, as both preparations show similar light dependent accumulation of fluorescent amine. It is concluded that the pattern of energy transduction in Plectonema photosynthetic lamellae is similar to that of chloroplast thylakoid membranes and not to that of bacterial cytoplasmic membranes. The evolutionary implications of the findings are discussed and a model for the directionality of H+ movements in the whole cell is presented.", "contents": "Energy transduction in the photosynthetic membranes of the cyanobacterium (blue-green alga) P-lectonema boryanum. Membrane preparations isolated from the photosynthetic lamellae of the cyanobacterium Plectonema boryanum generate upon illumination  a transmembrane pH gradient of approximately 2 to 3 pH units (acid inside), as determined from the distribution of either fluorescent or radioactive amines (9 aminoacridine and [14C]methylamine, respectively). Using the distribution of permeant ions to measure the electrical potential across the membrane, it was found that the latter is practically nil under conditions in which the deltapH is formed and photophosphorylation takes place. In agreement with the above findings cyclic photophosphorylation in this membrane preparation is inhibited by agents shown to collapse the deltapH but not by agents which should collapse the electrical potential. It is deduced that the pattern of proton movement in the photosynthetic lamellae of intact Plectonema spheroplasts corresponds to that of the cell-free membrane system, as both preparations show similar light dependent accumulation of fluorescent amine. It is concluded that the pattern of energy transduction in Plectonema photosynthetic lamellae is similar to that of chloroplast thylakoid membranes and not to that of bacterial cytoplasmic membranes. The evolutionary implications of the findings are discussed and a model for the directionality of H+ movements in the whole cell is presented."}
{"id": "PMID:25284", "title": "The transport of L-alanine by the hamster kidney cell line BHK-21-C13.", "content": "The uptake of L-alanine into BHK21-C13 cells in culture has been studied. This amino acid appears to be transported essentially via a relatively low affinity, high capacity, sodium ion dependent transport system. Inhibition studies using other amino acids or their analogues provided information about the specificity of this system. This alanine transport system was shown to exhibit a broad substrate specificity and appeared to be capable of transporting most naturally occurring neutral alpha-amino acids. Kinetic studies of the inhibition of L-alanine uptake also indicated the presence of a second neutral amino acid transport system capable of transporting this amino acid. However, it is unlikely that this second uptake system contributes greatly to L-alanine uptake. Inhibition of the uptake of L-leucine indicated that this transport system has a similar specificity to the \"L\"-system initially described for Ehrlich ascites carcinoma cells.", "contents": "The transport of L-alanine by the hamster kidney cell line BHK-21-C13. The uptake of L-alanine into BHK21-C13 cells in culture has been studied. This amino acid appears to be transported essentially via a relatively low affinity, high capacity, sodium ion dependent transport system. Inhibition studies using other amino acids or their analogues provided information about the specificity of this system. This alanine transport system was shown to exhibit a broad substrate specificity and appeared to be capable of transporting most naturally occurring neutral alpha-amino acids. Kinetic studies of the inhibition of L-alanine uptake also indicated the presence of a second neutral amino acid transport system capable of transporting this amino acid. However, it is unlikely that this second uptake system contributes greatly to L-alanine uptake. Inhibition of the uptake of L-leucine indicated that this transport system has a similar specificity to the \"L\"-system initially described for Ehrlich ascites carcinoma cells."}
{"id": "PMID:25285", "title": "Coordinacy of lysosomal enzyme excretion in human urine.", "content": "Assay conditions have been developed for the determination of urinary beta-glucuronidase, beta-galactosidase, alpha-galactosidase, and beta-hexosaminidase using fluorometric substrates. The assay conditions for beta-glucuronidase overcome interference by both low and high molecular weight inhibitors, a problem that has confused earlier studies of enzyme excretion. The four lysosomal enzymes are excreted corrdinately: although their absolute levels (in units per milligram of creatinine) vary during the day and from one day to the next, the ratio of one enzyme to another remains relatively constant. The lack of correlation betweem plasma and urine enzyme levels, together with the high molecular weights of these enzymes, suggests that the urinary enzymes are not derived by glomerular filtration. The lack of coordinacy with lactate dehydrogenase suggests they are not derived from exfoliated cells. by analogy with experimental animals, they may be derived from lysosomes extruded into the lumen of the proximal tubule by epithelial cells. There is considerable variation among a population of 125 healthy adult subjects for total enzyme excretion. Both total enzyme excretion and coordinacy ratios are log-normally distributed, suggesting that they are the resultants of many factors, each of which has a relative, or proportional, effect on enzyme excretion. About one-half the population variation resides in a process common to the excretion of all four enzymes (possibly the lysosome extrusion pathway), and about one-half resides in factors affecting each enzyme independently.", "contents": "Coordinacy of lysosomal enzyme excretion in human urine. Assay conditions have been developed for the determination of urinary beta-glucuronidase, beta-galactosidase, alpha-galactosidase, and beta-hexosaminidase using fluorometric substrates. The assay conditions for beta-glucuronidase overcome interference by both low and high molecular weight inhibitors, a problem that has confused earlier studies of enzyme excretion. The four lysosomal enzymes are excreted corrdinately: although their absolute levels (in units per milligram of creatinine) vary during the day and from one day to the next, the ratio of one enzyme to another remains relatively constant. The lack of correlation betweem plasma and urine enzyme levels, together with the high molecular weights of these enzymes, suggests that the urinary enzymes are not derived by glomerular filtration. The lack of coordinacy with lactate dehydrogenase suggests they are not derived from exfoliated cells. by analogy with experimental animals, they may be derived from lysosomes extruded into the lumen of the proximal tubule by epithelial cells. There is considerable variation among a population of 125 healthy adult subjects for total enzyme excretion. Both total enzyme excretion and coordinacy ratios are log-normally distributed, suggesting that they are the resultants of many factors, each of which has a relative, or proportional, effect on enzyme excretion. About one-half the population variation resides in a process common to the excretion of all four enzymes (possibly the lysosome extrusion pathway), and about one-half resides in factors affecting each enzyme independently."}
{"id": "PMID:25286", "title": "Diminished spectrin extraction from ATP-depleted human erythrocytes. Evidence relating spectrin to changes in erythrocyte shape and deformability.", "content": "We measured spectrin \"extractability\" in erythrocytes which were metabolically depleted by incubation at 37 degrees C in plasma or glucose-free buffers. Membranes were extracted with 1 mM EDTA (pH 8, 40 h, 4 degrees C) and analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. This procedure solubilized 85--90% of the spectrin, actin, and residual hemoglobin from ghosts of fresh erythrocytes. In incubated erythrocytes, inextractable spectrin rapidly accumulated when ATP concentrations fell below 0--15% of normal. In severely depleted cells, 60--90% of the total ghost spectrin became inextractable. Inextractability was not abolished by physically disrupting the ghost before extraction, but was reversed when erythrocyte ATP was replenished with adenosine. The accumulation of inextractable spectrin correlated temporally with the increase in apparent membrane deformability and the increases in erythrocyte vicosity, calcium content, sodium gain, and potassium loss characteristic of ATP-depleted erythrocytes. No change in integral membrane protein topography (assessed by the distribution of intramembranous particles and concanavalin A surface-binding sites) was detected in depleted cells. Analogous changes were observed in erythrocytes exposed to extremes of pH and temperature. When the pH in the erythrocyte interior fell below 5.5, a pH where spectrin was aggregated and isoelectrically precipitated, erythrocyte and ghost viscosity increased coincident with a marked decrease in spectrin extractability. Similarly above 49 degrees C, a temperature where spectrin was denatured and precipitated, erythrocyte viscosity rose as inextractable spectrin accumulated. These observations provide direct evidence of a change in the physical state of spectrin associated with a change in erythrocyte shape and deformability. They support the concept that erythrocyte shape and deformability are largely determined by the shape and deformability of the spectrin-actin protein meshwork which laminates the inner membrane surface.", "contents": "Diminished spectrin extraction from ATP-depleted human erythrocytes. Evidence relating spectrin to changes in erythrocyte shape and deformability. We measured spectrin \"extractability\" in erythrocytes which were metabolically depleted by incubation at 37 degrees C in plasma or glucose-free buffers. Membranes were extracted with 1 mM EDTA (pH 8, 40 h, 4 degrees C) and analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. This procedure solubilized 85--90% of the spectrin, actin, and residual hemoglobin from ghosts of fresh erythrocytes. In incubated erythrocytes, inextractable spectrin rapidly accumulated when ATP concentrations fell below 0--15% of normal. In severely depleted cells, 60--90% of the total ghost spectrin became inextractable. Inextractability was not abolished by physically disrupting the ghost before extraction, but was reversed when erythrocyte ATP was replenished with adenosine. The accumulation of inextractable spectrin correlated temporally with the increase in apparent membrane deformability and the increases in erythrocyte vicosity, calcium content, sodium gain, and potassium loss characteristic of ATP-depleted erythrocytes. No change in integral membrane protein topography (assessed by the distribution of intramembranous particles and concanavalin A surface-binding sites) was detected in depleted cells. Analogous changes were observed in erythrocytes exposed to extremes of pH and temperature. When the pH in the erythrocyte interior fell below 5.5, a pH where spectrin was aggregated and isoelectrically precipitated, erythrocyte and ghost viscosity increased coincident with a marked decrease in spectrin extractability. Similarly above 49 degrees C, a temperature where spectrin was denatured and precipitated, erythrocyte viscosity rose as inextractable spectrin accumulated. These observations provide direct evidence of a change in the physical state of spectrin associated with a change in erythrocyte shape and deformability. They support the concept that erythrocyte shape and deformability are largely determined by the shape and deformability of the spectrin-actin protein meshwork which laminates the inner membrane surface."}
{"id": "PMID:25289", "title": "Alpah-adrenergic receptor modulation of beta-adrenergic, adenosine and prostaglandin E1 increased adenosine 3':5'-cyclic monophosphate levels in primary cultures of glia.", "content": "Beta-adrenergic agonists, adenosine and prostaglandin E1 increased the level of adenosine 3':5'-monophosphate (cAMP) in glial cultures prepared from rat cerebral cortical tissue. In addition to these physiological effectors, cholera toxin also increased cAMP levels in these cultures. The accumulation of cAMP in response to each of these agen-s, including cholera toxin, was partially blocked (50--80%) by simultaneous alpha-adrenergic receptor stimulation. Basal levels of cAMP were not affected by alpha-adrenergic agonists. These results indicate that in glia, alpha-adrenergic receptors may serve to modulate the level of cAMP which normally accumulates in response to a number of neurohumoral substances. The modulatory effect of alpha-adrenergic agents does not appear to reduce cAMP accumulation by activating phosphodiesterase since the effect was not blocked by a potent inhibitor of this enzymemthe results suggest that the modulatory effect of alpha-adrenergic receptor activation results from an interaction which takes place at some point in between adenylate cyclase-associated-membrane receptors and the enzymatic degradation of cAMP.", "contents": "Alpah-adrenergic receptor modulation of beta-adrenergic, adenosine and prostaglandin E1 increased adenosine 3':5'-cyclic monophosphate levels in primary cultures of glia. Beta-adrenergic agonists, adenosine and prostaglandin E1 increased the level of adenosine 3':5'-monophosphate (cAMP) in glial cultures prepared from rat cerebral cortical tissue. In addition to these physiological effectors, cholera toxin also increased cAMP levels in these cultures. The accumulation of cAMP in response to each of these agen-s, including cholera toxin, was partially blocked (50--80%) by simultaneous alpha-adrenergic receptor stimulation. Basal levels of cAMP were not affected by alpha-adrenergic agonists. These results indicate that in glia, alpha-adrenergic receptors may serve to modulate the level of cAMP which normally accumulates in response to a number of neurohumoral substances. The modulatory effect of alpha-adrenergic agents does not appear to reduce cAMP accumulation by activating phosphodiesterase since the effect was not blocked by a potent inhibitor of this enzymemthe results suggest that the modulatory effect of alpha-adrenergic receptor activation results from an interaction which takes place at some point in between adenylate cyclase-associated-membrane receptors and the enzymatic degradation of cAMP."}
{"id": "PMID:25287", "title": "Diazepam and lorazepam for intravenous surgical premedication.", "content": "Diazepam, 10 and 20 mg, and 2 and 4 mg lorazepam were studied as intravenous surgical premedicants in 120 patients. Relief of anxiety, sedation, patient acceptance, lack of recall, and side effects were the variables evaluated. Both diazepam and lorazepam proved to be excellent surgical premedicants. The basic difference between the two drugs is temporal. Both medications produce similar relief of anxiety, sedation, patient acceptance, and lack of recall. The clinical effects of intravenous diazepam peaks in 2 to 3 minutes and diminishes thereafter. Intravenous lorazepam has a latent period of 8 to 15 minutes, with increasing effects at 15 to 30 minutes.", "contents": "Diazepam and lorazepam for intravenous surgical premedication. Diazepam, 10 and 20 mg, and 2 and 4 mg lorazepam were studied as intravenous surgical premedicants in 120 patients. Relief of anxiety, sedation, patient acceptance, lack of recall, and side effects were the variables evaluated. Both diazepam and lorazepam proved to be excellent surgical premedicants. The basic difference between the two drugs is temporal. Both medications produce similar relief of anxiety, sedation, patient acceptance, and lack of recall. The clinical effects of intravenous diazepam peaks in 2 to 3 minutes and diminishes thereafter. Intravenous lorazepam has a latent period of 8 to 15 minutes, with increasing effects at 15 to 30 minutes."}
{"id": "PMID:25291", "title": "Loss of carbofuran from rice paddy water: chemical and physical factors.", "content": "The loss of carbofuran was studied from rice paddy water treated with a granular formulation of the insecticide, and from ponds filled with drainage from the paddy. The average half-life (t 1/2) for carbofuran loss was 57 hr. Controlled experiments indicated that pH was the predominating factor governing carbofuran loss from water in the environment studied. The loss due to hydrolysis was over 700 times more rapid at pH (t 1/2 = 1.2 hr.) than at pH (t 1/2 = 864 hr.) in buffered deionized water. The average pH of the rice paddy was 8, but diurnal fluctuations of 7 to 9.5 are common in similar environments. Impurities in the water, sunlight, and temperature influence the rate of carbofuran loss but not nearly so much as pH. There was no evidence for significant loss due to evaporation or oxidation. The results have important implications for the duration of the insecticide's activity and the effect on fish within or downstream from treated paddies.", "contents": "Loss of carbofuran from rice paddy water: chemical and physical factors. The loss of carbofuran was studied from rice paddy water treated with a granular formulation of the insecticide, and from ponds filled with drainage from the paddy. The average half-life (t 1/2) for carbofuran loss was 57 hr. Controlled experiments indicated that pH was the predominating factor governing carbofuran loss from water in the environment studied. The loss due to hydrolysis was over 700 times more rapid at pH (t 1/2 = 1.2 hr.) than at pH (t 1/2 = 864 hr.) in buffered deionized water. The average pH of the rice paddy was 8, but diurnal fluctuations of 7 to 9.5 are common in similar environments. Impurities in the water, sunlight, and temperature influence the rate of carbofuran loss but not nearly so much as pH. There was no evidence for significant loss due to evaporation or oxidation. The results have important implications for the duration of the insecticide's activity and the effect on fish within or downstream from treated paddies."}
{"id": "PMID:25292", "title": "Preservation of organophosphorous pesticides in water samples.", "content": "Four techniques were studied for capacity to preserve sixteen organophosphorous pesticides in distilled water and in creek water. A technique using chloroform effectively preserved all sixteen pesticides for the three weeks of the study and refrigeration was effective for fourteen of the pesticides, but buffers of pH 4 and pH 7 appeared undependable as preservatives.", "contents": "Preservation of organophosphorous pesticides in water samples. Four techniques were studied for capacity to preserve sixteen organophosphorous pesticides in distilled water and in creek water. A technique using chloroform effectively preserved all sixteen pesticides for the three weeks of the study and refrigeration was effective for fourteen of the pesticides, but buffers of pH 4 and pH 7 appeared undependable as preservatives."}
{"id": "PMID:25288", "title": "Long-term hypnotic efficacy and safety of triazolam and flurazepam.", "content": "Both triazolam and flurazepam are effective hypnotics when administered nightly for 12 consecutive weeks. However, at the dosages tested, 0.6 mg triazolam had a significantly faster onset of activity than 30 mg flurazepam. Long-term administration of either treatment did not influence the patient's capability to recognize the difference between active drug and placebo. This supports the conclusion that there was no tolerance development on either treatment. There were no deleterious effects attributable to either treatment as measured by the 35-Item Hopkins Symptom Checklist or by physical examinations, laboratory tests, ECGs, and ophthalmologic examinations. Side effects occurred more often on flurazepam than on triazolam, and the number of patients experiencing side effects was significantly higher in the flurazepam group. Drowsiness and grogginess were reported most frequently on both treatments, and the number of patients reporting drowsiness or grogginess was also significantly higher in the flurazepam group.", "contents": "Long-term hypnotic efficacy and safety of triazolam and flurazepam. Both triazolam and flurazepam are effective hypnotics when administered nightly for 12 consecutive weeks. However, at the dosages tested, 0.6 mg triazolam had a significantly faster onset of activity than 30 mg flurazepam. Long-term administration of either treatment did not influence the patient's capability to recognize the difference between active drug and placebo. This supports the conclusion that there was no tolerance development on either treatment. There were no deleterious effects attributable to either treatment as measured by the 35-Item Hopkins Symptom Checklist or by physical examinations, laboratory tests, ECGs, and ophthalmologic examinations. Side effects occurred more often on flurazepam than on triazolam, and the number of patients experiencing side effects was significantly higher in the flurazepam group. Drowsiness and grogginess were reported most frequently on both treatments, and the number of patients reporting drowsiness or grogginess was also significantly higher in the flurazepam group."}
{"id": "PMID:25304", "title": "Biological characteristics of peptidoglycans of group A streptococcus and some other bacterial species. I. Tolerance and effect of antibody in fever response, and heart damaging effect in rabbits.", "content": "Induced tolerance to the pyrogenic action of group A streptococcus peptidoglycan decreased after one week and was no longer detectable after the second week. However, one or two further doses of peptidoglycan rapidly restored the tolerance. The passive transfer of plasma from rabbits tolerant to streptococcus peptidoglycan to nontolerant animals failed to transfer tolerance. Antiserum to streptococcus peptidoglycan neutralized the pyrogenic effect of not only streptococcus but also staphylococcus and pneumococcus peptidoglycan; it did not influence the febrile response to endotoxin. Histopathologic changes in the rabbit heart produced by the intravenous injection of staphylococcus or pneumococcus peptidoglycans were similar and were characterized by various stages of degeneration and necrosis. The changes were less pronounced than after streptococcus peptidoglycan. Antiserum to streptococcus peptidoglycan had modest or no counteracting effect on the development of heart alterations after staphylococcus or pneumococcus peptidoglycan.", "contents": "Biological characteristics of peptidoglycans of group A streptococcus and some other bacterial species. I. Tolerance and effect of antibody in fever response, and heart damaging effect in rabbits. Induced tolerance to the pyrogenic action of group A streptococcus peptidoglycan decreased after one week and was no longer detectable after the second week. However, one or two further doses of peptidoglycan rapidly restored the tolerance. The passive transfer of plasma from rabbits tolerant to streptococcus peptidoglycan to nontolerant animals failed to transfer tolerance. Antiserum to streptococcus peptidoglycan neutralized the pyrogenic effect of not only streptococcus but also staphylococcus and pneumococcus peptidoglycan; it did not influence the febrile response to endotoxin. Histopathologic changes in the rabbit heart produced by the intravenous injection of staphylococcus or pneumococcus peptidoglycans were similar and were characterized by various stages of degeneration and necrosis. The changes were less pronounced than after streptococcus peptidoglycan. Antiserum to streptococcus peptidoglycan had modest or no counteracting effect on the development of heart alterations after staphylococcus or pneumococcus peptidoglycan."}
{"id": "PMID:25305", "title": "Studies on the mitogen responses of germfree allogeneic chimeras. II. Maturation of two cell types and partial restoration of responsiveness of the short-term chimeras.", "content": "Germfree allogeneic bone marrow chimeras (ABMC) were produced by the i.v. injection of approximately 10(7) bone marrow cells from germfree DBA/2 mice into lethally irradiated germfree C3H mice. In the germfree state, the short-term ABMC showed no histologic signs of graft-vs-host reactions (GVHR), yet splenic lymphocytes were unable to respond to PHA, Con A, or SRBC. Attempts to remove responsiveness by the implantation of a DBA/2 thymus under the host kidney capsule also resulted in failure. However, when the donor thymus was enclosed in a cell-impermeable chamber to eliminate a GVH reaction, responsiveness to Con A was restored. The PHA and SRBC responses were unaffected by this treatment. Daily injections of thymosin caused both an increased Con A response and increased numbers of PFC, although the PHA response was again unaffected. Thus, soluble substances from thymic tissue can be used to overcome partially the histocompatibility barrier present in the ABMC that affects at least two different functional cell populations.", "contents": "Studies on the mitogen responses of germfree allogeneic chimeras. II. Maturation of two cell types and partial restoration of responsiveness of the short-term chimeras. Germfree allogeneic bone marrow chimeras (ABMC) were produced by the i.v. injection of approximately 10(7) bone marrow cells from germfree DBA/2 mice into lethally irradiated germfree C3H mice. In the germfree state, the short-term ABMC showed no histologic signs of graft-vs-host reactions (GVHR), yet splenic lymphocytes were unable to respond to PHA, Con A, or SRBC. Attempts to remove responsiveness by the implantation of a DBA/2 thymus under the host kidney capsule also resulted in failure. However, when the donor thymus was enclosed in a cell-impermeable chamber to eliminate a GVH reaction, responsiveness to Con A was restored. The PHA and SRBC responses were unaffected by this treatment. Daily injections of thymosin caused both an increased Con A response and increased numbers of PFC, although the PHA response was again unaffected. Thus, soluble substances from thymic tissue can be used to overcome partially the histocompatibility barrier present in the ABMC that affects at least two different functional cell populations."}
{"id": "PMID:25309", "title": "Tyrosine aminotransferase in AKR/J albino and C57BL/6J black mouse skin.", "content": "L-Tyrosine aminotransferase is present in a high speed supernatant fraction of skin homogenate of AKR/J albino and C57BL/6J black mice. The conversion of tyrosine to p-hydroxyphenylpyruvate was shown to be catalyzed by an aminotransferase by the following observations: the reaction was partially dependent on the presence of low concentrations of alpha-ketoglutarate; catalase was ineffective in increasing the yield of p-hydroxyphenylpyruvate; there was potent inhibition by typical inhibitors of pyridoxal phosphate enzymes and of rat liver tyrosine aminotransferase; there was no inhibition by inhibitors of L-amino acid oxidase; and there was no oxidation of L-leucine, the best substrate for rat kidney L-amino acid oxidase. The aminotransferase was stimulated by mercaptoethanol and was inhibited by high concentrations of alpha-ketoglutarate. The apparent Km for tyrosine was 5 X 10(-3) M and the molecular weight, determined by sucrose density gradient centrifugation, was 150-200,000. Dopa was also transaminated by the crude enzyme. No tyrosine aminotransferase could be detected in extracts of hamster melanoma.", "contents": "Tyrosine aminotransferase in AKR/J albino and C57BL/6J black mouse skin. L-Tyrosine aminotransferase is present in a high speed supernatant fraction of skin homogenate of AKR/J albino and C57BL/6J black mice. The conversion of tyrosine to p-hydroxyphenylpyruvate was shown to be catalyzed by an aminotransferase by the following observations: the reaction was partially dependent on the presence of low concentrations of alpha-ketoglutarate; catalase was ineffective in increasing the yield of p-hydroxyphenylpyruvate; there was potent inhibition by typical inhibitors of pyridoxal phosphate enzymes and of rat liver tyrosine aminotransferase; there was no inhibition by inhibitors of L-amino acid oxidase; and there was no oxidation of L-leucine, the best substrate for rat kidney L-amino acid oxidase. The aminotransferase was stimulated by mercaptoethanol and was inhibited by high concentrations of alpha-ketoglutarate. The apparent Km for tyrosine was 5 X 10(-3) M and the molecular weight, determined by sucrose density gradient centrifugation, was 150-200,000. Dopa was also transaminated by the crude enzyme. No tyrosine aminotransferase could be detected in extracts of hamster melanoma."}
{"id": "PMID:25310", "title": "The relationships among arterial oxygen flow rate, oxygen binding by hemoglobin, and oxygen utilization in chronic cardiac decompensation.", "content": "We have examined the interrelationships among CaO2, blood flow, oxygen binding by hemoglobin, and VO2 in cardiac patients with and without chronic cardiac decompensation. We have quantified the role that decreased oxygen-binding to hemoglobin may play in maintaining VO2 in the presence of low systemic blood flow rates. The volume rate of oxygen delivery to tissues was expressed as the OFIa, the product of CO2 and blood flow. OFIa varied from 738 to 262 ml/min/m2, whereas VO2 varied from 170 to 117 ml/min/m2. Thus, in the patients with lowest OFIa (63% below the highest OFIa), VO2 was only down 19%. VO2 was maintained because the extraction of oxygen rose from about 20% to 50% in close association with the decrease in OFIa. Oxygen binding to hemoglobin was lower in patients with the lowest OFIa--and therefore, at in vivo conditions of pH, PCO2, and temperature, P50 in vivo was higher. The resulting facilitation of oxygen release at the PO2 of tissue capillaries could explain about one third of the observed increment in oxygen extraction in patients with low OFIa. An alternative interpretation is that a high P50 in vivo minimizes the reduction in PVO2 needed to maintain VO2 when increased proportional extraction of O2 compensates for decreased OFIa.", "contents": "The relationships among arterial oxygen flow rate, oxygen binding by hemoglobin, and oxygen utilization in chronic cardiac decompensation. We have examined the interrelationships among CaO2, blood flow, oxygen binding by hemoglobin, and VO2 in cardiac patients with and without chronic cardiac decompensation. We have quantified the role that decreased oxygen-binding to hemoglobin may play in maintaining VO2 in the presence of low systemic blood flow rates. The volume rate of oxygen delivery to tissues was expressed as the OFIa, the product of CO2 and blood flow. OFIa varied from 738 to 262 ml/min/m2, whereas VO2 varied from 170 to 117 ml/min/m2. Thus, in the patients with lowest OFIa (63% below the highest OFIa), VO2 was only down 19%. VO2 was maintained because the extraction of oxygen rose from about 20% to 50% in close association with the decrease in OFIa. Oxygen binding to hemoglobin was lower in patients with the lowest OFIa--and therefore, at in vivo conditions of pH, PCO2, and temperature, P50 in vivo was higher. The resulting facilitation of oxygen release at the PO2 of tissue capillaries could explain about one third of the observed increment in oxygen extraction in patients with low OFIa. An alternative interpretation is that a high P50 in vivo minimizes the reduction in PVO2 needed to maintain VO2 when increased proportional extraction of O2 compensates for decreased OFIa."}
{"id": "PMID:25311", "title": "Allosteric modifiers of fish hemoglobins: in vitro and in vivo studies of the effect of ambient oxygen and pH on erythrocyte ATP concentrations.", "content": "Fundulus heteroclitus decreases erythrocyte adenosine triphosphate and increases blood hematocrit when acclimated to hypoxic conditions. A defined medium has been developed which allows isolated F. heteroclitus erythrocytes to be maintained for several hours without an appreciable loss of cellular ATP. The effect of oxygen tension, pH and metabolic inhibitors on the cellular concentration of ATP of fish red cells has been investigated as an in vitro model to explain in vivo responses to environmental changes. The isolated red cells significantly decrease their ATP/Hb molar ratio when exposed either to anaerobiosis or metabolic inhibitors. It is concluded that the in vivo response is mediated at the red cell level via decreased oxidative phosphorylation in the presence of low environmental oxygen. The length of time necessary to elicit the responce both in vivo and in vitro is also discussed.", "contents": "Allosteric modifiers of fish hemoglobins: in vitro and in vivo studies of the effect of ambient oxygen and pH on erythrocyte ATP concentrations. Fundulus heteroclitus decreases erythrocyte adenosine triphosphate and increases blood hematocrit when acclimated to hypoxic conditions. A defined medium has been developed which allows isolated F. heteroclitus erythrocytes to be maintained for several hours without an appreciable loss of cellular ATP. The effect of oxygen tension, pH and metabolic inhibitors on the cellular concentration of ATP of fish red cells has been investigated as an in vitro model to explain in vivo responses to environmental changes. The isolated red cells significantly decrease their ATP/Hb molar ratio when exposed either to anaerobiosis or metabolic inhibitors. It is concluded that the in vivo response is mediated at the red cell level via decreased oxidative phosphorylation in the presence of low environmental oxygen. The length of time necessary to elicit the responce both in vivo and in vitro is also discussed."}
{"id": "PMID:25317", "title": "Stronglyoides ransomi: factors influencing the in vitro development of the free-living generation.", "content": "Among the progeny of parasitic females of Strongyloides ransomi, ransomi, males did not appear in significant numbers until the 7th week of infection in cases of simple infection, and until the 3rd week of infection in cases of multiple infection. The appearance of males was attributed to the effect of host immunity, the physiological ageing of the parasitic females, or both. Type of culture substrate and other cultural conditions did not influence the percent of larvae developing into males. Sex of larvae was determined prior to hatching, probably during oogenesis or embryogenesis. Culture conditions influenced the direction of development of female larvae. An initial pH below 5.9 or above 7.2 favored differentiation of larvae into infective larvae, whereas, intermediate initial pH levels favored development of free-living females. Baby pig substrate, autoclaved substrate, and substrate washed free of soluble chemicals (adverse cultural conditions)  promoted differentiation toward infective larvae. Adult pig substrate, nonautoclaved substrate and unwashed substrate promoted differentiation toward free-living females. In general, adverse conditions inside the host and favor an indirect life cycle.", "contents": "Stronglyoides ransomi: factors influencing the in vitro development of the free-living generation. Among the progeny of parasitic females of Strongyloides ransomi, ransomi, males did not appear in significant numbers until the 7th week of infection in cases of simple infection, and until the 3rd week of infection in cases of multiple infection. The appearance of males was attributed to the effect of host immunity, the physiological ageing of the parasitic females, or both. Type of culture substrate and other cultural conditions did not influence the percent of larvae developing into males. Sex of larvae was determined prior to hatching, probably during oogenesis or embryogenesis. Culture conditions influenced the direction of development of female larvae. An initial pH below 5.9 or above 7.2 favored differentiation of larvae into infective larvae, whereas, intermediate initial pH levels favored development of free-living females. Baby pig substrate, autoclaved substrate, and substrate washed free of soluble chemicals (adverse cultural conditions)  promoted differentiation toward infective larvae. Adult pig substrate, nonautoclaved substrate and unwashed substrate promoted differentiation toward free-living females. In general, adverse conditions inside the host and favor an indirect life cycle."}
{"id": "PMID:25318", "title": "A simple quantitative technique for testing behavioral responses of Schistosoma mansoni miracidia to chemicals.", "content": "We describe a new technique for testing responses of Schistosoma mansoni miracidia to chemicals. Miracidia in spring water were placed in a chamber shaped like the Greek letter phi. Small volumes of test chemicals were inoculated into one side of the chamber. After 30 sec a dam was inserted to bisect the chamber and the percentage of miracidia on the inoculated side was calculated. Reproducible quantitative results were obtained using the known miracidial stimulants, snail-conditioned water (Biomphalaria glabrata) and Mg2+; up to 80% of the miracidia were recovered on the inoculated side of the chamber. Other substances also stimulated miracidia: several inorganic cations, 4 neurotransmitters, 3 acetycholine antagonists, and 1 acetycholine agonist. Modifying the technique by testing stimulants in altered chemical \"backgrounds\" allowed us to test for inhibitors of miracidial responses. Assays of the Mg2+ content of several of the test solutions indicated that their stimulatory or inhibitory effects could not be ascribed to Mg2+ contamination. However, results obtained with neurotransmitters and drugs were not sufficiently consistent to implicate specific neurotransmitters in the mechanism by which miracidia detect and respond to stimulants in snail-conditioned water.", "contents": "A simple quantitative technique for testing behavioral responses of Schistosoma mansoni miracidia to chemicals. We describe a new technique for testing responses of Schistosoma mansoni miracidia to chemicals. Miracidia in spring water were placed in a chamber shaped like the Greek letter phi. Small volumes of test chemicals were inoculated into one side of the chamber. After 30 sec a dam was inserted to bisect the chamber and the percentage of miracidia on the inoculated side was calculated. Reproducible quantitative results were obtained using the known miracidial stimulants, snail-conditioned water (Biomphalaria glabrata) and Mg2+; up to 80% of the miracidia were recovered on the inoculated side of the chamber. Other substances also stimulated miracidia: several inorganic cations, 4 neurotransmitters, 3 acetycholine antagonists, and 1 acetycholine agonist. Modifying the technique by testing stimulants in altered chemical \"backgrounds\" allowed us to test for inhibitors of miracidial responses. Assays of the Mg2+ content of several of the test solutions indicated that their stimulatory or inhibitory effects could not be ascribed to Mg2+ contamination. However, results obtained with neurotransmitters and drugs were not sufficiently consistent to implicate specific neurotransmitters in the mechanism by which miracidia detect and respond to stimulants in snail-conditioned water."}
{"id": "PMID:25319", "title": "Effect of diamfenetide on experimental infections of Fasciola hepatica in lambs: anthelmintic and clinical investigations.", "content": "The activity of diamfenetide (N,N'-[oxybis(2,1-ethan diyloxy-4,1-phenylene)] bis acetamide) was studied in lambs experimentally inoculated with Fasciola hepatica. The drug was given orally at a dose level of 100 mg/kg either 1,3,5,7, or 9 weeks postinoculation. It was 100% effective 1, 3, and 5 weeks postinoculation, 73% effective 7 weeks postinoculation, and 57% effective 9 weeks postinoculation. Serum gamma-glutamyl transpeptidase activity remained normal in all lambs for 5 weeks after infection; it then began to increase in infected, untreated lambs at 6 weeks, and had increased 5- to 6-fold 9 weeks postinoculation in infected lambs. This enzyme activity was the most sensitive hematologic parameter used in this test to detect hepatobiliary damage by the parasite. The drug was well tolerated at the dose level used.", "contents": "Effect of diamfenetide on experimental infections of Fasciola hepatica in lambs: anthelmintic and clinical investigations. The activity of diamfenetide (N,N'-[oxybis(2,1-ethan diyloxy-4,1-phenylene)] bis acetamide) was studied in lambs experimentally inoculated with Fasciola hepatica. The drug was given orally at a dose level of 100 mg/kg either 1,3,5,7, or 9 weeks postinoculation. It was 100% effective 1, 3, and 5 weeks postinoculation, 73% effective 7 weeks postinoculation, and 57% effective 9 weeks postinoculation. Serum gamma-glutamyl transpeptidase activity remained normal in all lambs for 5 weeks after infection; it then began to increase in infected, untreated lambs at 6 weeks, and had increased 5- to 6-fold 9 weeks postinoculation in infected lambs. This enzyme activity was the most sensitive hematologic parameter used in this test to detect hepatobiliary damage by the parasite. The drug was well tolerated at the dose level used."}
{"id": "PMID:25321", "title": "Effect of vehicles and other active ingredients on stability of hydrocortisone.", "content": "The stability of hydrocortisone in various types of vehicles, aqueous, water-washable (polyethylene glycol ointment base), and oil in water or water in oil-type emulsified vehicles, and in the presence of other ingredients, iodochlorhydroxyquin, menthol, and phenol, was studied under normal conditions (room temperature and weakly acidic pH). The study was conducted using a stability-indicating assay method, high-pressure liquid chromatography. The hydrocortisone was very unstable in water and water-washable ointment base. The addition of alcohol and glycerin to water had a stabilizing effect. Under drastic conditions (very acidic or very basic pH), hydrocortisone proved to be unstable only on the basic side. The data at higher temperatures confirmed that the decomposition in water and polyethylene glycol was pseudo-first order. The decomposition process appears to be different in the highly basic solution versus weakly acidic media or in water versus polyethylene glycol ointment base.", "contents": "Effect of vehicles and other active ingredients on stability of hydrocortisone. The stability of hydrocortisone in various types of vehicles, aqueous, water-washable (polyethylene glycol ointment base), and oil in water or water in oil-type emulsified vehicles, and in the presence of other ingredients, iodochlorhydroxyquin, menthol, and phenol, was studied under normal conditions (room temperature and weakly acidic pH). The study was conducted using a stability-indicating assay method, high-pressure liquid chromatography. The hydrocortisone was very unstable in water and water-washable ointment base. The addition of alcohol and glycerin to water had a stabilizing effect. Under drastic conditions (very acidic or very basic pH), hydrocortisone proved to be unstable only on the basic side. The data at higher temperatures confirmed that the decomposition in water and polyethylene glycol was pseudo-first order. The decomposition process appears to be different in the highly basic solution versus weakly acidic media or in water versus polyethylene glycol ointment base."}
{"id": "PMID:25322", "title": "Demonstration of penicillamine as a product in benzylpenicillenic acid degradation in neutral media using differential pulse polarography.", "content": "During the study of the temporal changes of benzylpenicillenic acid in aqueous buffers using differential pulse polarography, penicillamine was found to be a degradation product at neutral pH. Since this result was not previously reported, the effects of pH and buffer concentration on penicillamine formation were investigated. The amount of penicillamine produced was greatest under conditions producing maximum benzylpenicillenic acid stability. Penicillamine was not obtained from benzylpenicilloic acid, the reported degradation product of benzylpenicillenic acid at neutral pH. Penicillamine also was detected in penicillin G solutions of neutral pH. Therefore, it is suggested that penicillamine found in penicillin G solutions arises from benzylpenicillenic acid degradation which, in turn, is produced from penicillin G isomerization. A pathway is proposed to show that penicillamine originates from the UV-absorbing isomer of benzylpenicillenic acid.", "contents": "Demonstration of penicillamine as a product in benzylpenicillenic acid degradation in neutral media using differential pulse polarography. During the study of the temporal changes of benzylpenicillenic acid in aqueous buffers using differential pulse polarography, penicillamine was found to be a degradation product at neutral pH. Since this result was not previously reported, the effects of pH and buffer concentration on penicillamine formation were investigated. The amount of penicillamine produced was greatest under conditions producing maximum benzylpenicillenic acid stability. Penicillamine was not obtained from benzylpenicilloic acid, the reported degradation product of benzylpenicillenic acid at neutral pH. Penicillamine also was detected in penicillin G solutions of neutral pH. Therefore, it is suggested that penicillamine found in penicillin G solutions arises from benzylpenicillenic acid degradation which, in turn, is produced from penicillin G isomerization. A pathway is proposed to show that penicillamine originates from the UV-absorbing isomer of benzylpenicillenic acid."}
{"id": "PMID:25323", "title": "Effect of ionization on absorption of cephalosporins.", "content": "To explore the relative absorbabilities of different ionic forms of cephalosporins, the absorption rates of four compounds were measured in the pH 5-9 region using an in situ rat gut technique. Cephalexin, cephradine, and cephaloglycin have some oral activity, while 3-[(acetyloxy)methyl]-8-oxo-7-[[(4-oxo-1(4H-pyridinyl)acetyl]-amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (I) has insignificant oral activity. The pH-species profiles calculated from their ionization constants showed that cephalexin, cephradine, and cephaloglycin have a large proportion of uncharged molecules plus zwitterions in the pH range of the small intestine, while I exists as the anion throughout this range. When the species profiles are compared with the pH-absorption rate profiles for cephalexin, cephradine, and I, the results are consistent with a model in which the zwitterionic and/or uncharged forms of the molecules are well absorbed, whereas the anions show little or no absorption. Although it has a pH profile for zwitterions plus uncharged molecules similar to cephalexin, cephaloglycin shows poor absorption, suggesting that the ratio of uncharged molecules to zwitterions may be important in absorption.", "contents": "Effect of ionization on absorption of cephalosporins. To explore the relative absorbabilities of different ionic forms of cephalosporins, the absorption rates of four compounds were measured in the pH 5-9 region using an in situ rat gut technique. Cephalexin, cephradine, and cephaloglycin have some oral activity, while 3-[(acetyloxy)methyl]-8-oxo-7-[[(4-oxo-1(4H-pyridinyl)acetyl]-amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (I) has insignificant oral activity. The pH-species profiles calculated from their ionization constants showed that cephalexin, cephradine, and cephaloglycin have a large proportion of uncharged molecules plus zwitterions in the pH range of the small intestine, while I exists as the anion throughout this range. When the species profiles are compared with the pH-absorption rate profiles for cephalexin, cephradine, and I, the results are consistent with a model in which the zwitterionic and/or uncharged forms of the molecules are well absorbed, whereas the anions show little or no absorption. Although it has a pH profile for zwitterions plus uncharged molecules similar to cephalexin, cephaloglycin shows poor absorption, suggesting that the ratio of uncharged molecules to zwitterions may be important in absorption."}
{"id": "PMID:25324", "title": "Kinetics of digoxin stability in aqueous solution.", "content": "Digoxin hydrolysis was studied as a function of pH. Conversion of digoxin to digoxigenin was followed by high-pressure liquid chromatography and shown to proceed by the initial loss of one, two, or three sugars. The hydrolysis rate was directly proportional to parent drug concentration and hydrogen-ion activity. The individual hydrolysis rate constants of digoxin, digoxigenin bisdigitoxoside, and digoxigenin monodigitoxoside were determined by a simplex fitting procedure. Data are presented suggesting that at least some variation in the bioavailability of orally administered digoxin arises from observed variations in gastric pH; these variations influence the extent to which hydrolysis occurs and, thus, modify the composition of digoxin species available for absorption.", "contents": "Kinetics of digoxin stability in aqueous solution. Digoxin hydrolysis was studied as a function of pH. Conversion of digoxin to digoxigenin was followed by high-pressure liquid chromatography and shown to proceed by the initial loss of one, two, or three sugars. The hydrolysis rate was directly proportional to parent drug concentration and hydrogen-ion activity. The individual hydrolysis rate constants of digoxin, digoxigenin bisdigitoxoside, and digoxigenin monodigitoxoside were determined by a simplex fitting procedure. Data are presented suggesting that at least some variation in the bioavailability of orally administered digoxin arises from observed variations in gastric pH; these variations influence the extent to which hydrolysis occurs and, thus, modify the composition of digoxin species available for absorption."}
{"id": "PMID:25325", "title": "Spectroscopic approach to estimation of microequilibrium constants of prototropic reactions of aminobenzoic acids.", "content": "The microequilibrium constants of protolytic dissociation of diprotic acids, dihydric bases, or ampholytes such as the aminobenzoic acids, with dissimilar ionizing groups, can be estimated by spectrophotometric titration and measurement of the molar absorptivity at the long wavelength absorption maximum of simple alkylated derivatives. The method is applicable when the long wavelength absorption spectral bands of the tautomeric species are well resolved. Compared to the traditional method of estimating microequilibrium constants using the dissociation constants of alkylated derivatives, the proposed method is simpler, faster, and more accurate.", "contents": "Spectroscopic approach to estimation of microequilibrium constants of prototropic reactions of aminobenzoic acids. The microequilibrium constants of protolytic dissociation of diprotic acids, dihydric bases, or ampholytes such as the aminobenzoic acids, with dissimilar ionizing groups, can be estimated by spectrophotometric titration and measurement of the molar absorptivity at the long wavelength absorption maximum of simple alkylated derivatives. The method is applicable when the long wavelength absorption spectral bands of the tautomeric species are well resolved. Compared to the traditional method of estimating microequilibrium constants using the dissociation constants of alkylated derivatives, the proposed method is simpler, faster, and more accurate."}
{"id": "PMID:25326", "title": "Characterization of impurities in sulfasalazine.", "content": "The chemical structures of four impurities isolated from sulfasalazine were determined. Three impurities are the by-products of the reaction process in drug synthesis, i.e., during diazotization of sulfapyridine and during coupling with salicylic acid. Only one contaminant was identified as a starting material, sulfapyridine, in the drug synthesis. The four impurities were characterized as 2-[[p-(2-pyridylsulfamoyl)-phenyl]azo]hydroxybenzene (I), 3-[[P-(2-pyridylsulfamoyl) phenyl]-azo]salicylic acid (II), 5-[[p-[4-(2-pyridylanilino)]-N-phenyl]azo]salicylic acid (III), and sulfapyridine (IV). Compounds I-III are novel molecules, and IV is the precursor of sulfasalazine. The isolation of the impurities was accomplished by TLC and liquid extraction procedures. The methods used to characterize the impurities were a combination of IR, UV, and NMR spectroscopy, mass spectrometry, and TLC. For I and III, comparisons also were made with the synthesized materials to supplement the evaluation.", "contents": "Characterization of impurities in sulfasalazine. The chemical structures of four impurities isolated from sulfasalazine were determined. Three impurities are the by-products of the reaction process in drug synthesis, i.e., during diazotization of sulfapyridine and during coupling with salicylic acid. Only one contaminant was identified as a starting material, sulfapyridine, in the drug synthesis. The four impurities were characterized as 2-[[p-(2-pyridylsulfamoyl)-phenyl]azo]hydroxybenzene (I), 3-[[P-(2-pyridylsulfamoyl) phenyl]-azo]salicylic acid (II), 5-[[p-[4-(2-pyridylanilino)]-N-phenyl]azo]salicylic acid (III), and sulfapyridine (IV). Compounds I-III are novel molecules, and IV is the precursor of sulfasalazine. The isolation of the impurities was accomplished by TLC and liquid extraction procedures. The methods used to characterize the impurities were a combination of IR, UV, and NMR spectroscopy, mass spectrometry, and TLC. For I and III, comparisons also were made with the synthesized materials to supplement the evaluation."}
{"id": "PMID:25327", "title": "In vitro evidence for ipecac inactivation by activated charcoal.", "content": "The in vitro adsorption of the alkaloid emetine, a primary constituent of ipecac, on activated charcoal was studied. The results support the supposition that syrup of ipecac should not be given to counteract poisonings if activated charcoal is also to be administered.", "contents": "In vitro evidence for ipecac inactivation by activated charcoal. The in vitro adsorption of the alkaloid emetine, a primary constituent of ipecac, on activated charcoal was studied. The results support the supposition that syrup of ipecac should not be given to counteract poisonings if activated charcoal is also to be administered."}
{"id": "PMID:25328", "title": "Determination of desmethyldiazepam in plasma by electron-capture GLC: application to pharmacokinetic studies of clorazepate.", "content": "Plasma desmethyldiazepam concentrations were quantitated by a rapid and sensitive technique using electron-capture GLC. Following addition of diazepam as the internal standard, plasma is extracted at physiological pH into benzene-isoamyl alcohol. The extract is evaporated to dryness and reconstituted with toluene-isoamyl alcohol prior to chromatography. Both diazepam and desmethyldiazepam are quantitatively extracted. The variation of identical samples is 5%, and the sensitivity is 5 ng of desmethyldiazepam/ml of original sample. The method is applicable to pharmacokinetic studies of clorazepate, a benzodiazepine derivative transformed to desmethyldiazepam prior to absorption.", "contents": "Determination of desmethyldiazepam in plasma by electron-capture GLC: application to pharmacokinetic studies of clorazepate. Plasma desmethyldiazepam concentrations were quantitated by a rapid and sensitive technique using electron-capture GLC. Following addition of diazepam as the internal standard, plasma is extracted at physiological pH into benzene-isoamyl alcohol. The extract is evaporated to dryness and reconstituted with toluene-isoamyl alcohol prior to chromatography. Both diazepam and desmethyldiazepam are quantitatively extracted. The variation of identical samples is 5%, and the sensitivity is 5 ng of desmethyldiazepam/ml of original sample. The method is applicable to pharmacokinetic studies of clorazepate, a benzodiazepine derivative transformed to desmethyldiazepam prior to absorption."}
{"id": "PMID:25329", "title": "In vitro evaluation of three commercial sustained-release papaverine hydrochloride products.", "content": "Three commercial sustained-release papaverine hydrochloride products in the form of microencapsulated pellets were evaluated. Three different dissolution apparatuses were used: a continuous flow apparatus, the USP rotating basket apparatus, and a modified reciprocating basket apparatus. The frequency rate of the reciprocating basket apparatus could be varied from 0 to 31 strokes/min. Salicylic acid compacts were used as a standard to characterize each apparatus. A linear log--log correlation between dissolution rate and apparatus speed or flow rate was obtained. Release of papaverine hydrochloride from the commercial preparations was affected significantly by the pH of the dissolution media but not by the agitation intensity.", "contents": "In vitro evaluation of three commercial sustained-release papaverine hydrochloride products. Three commercial sustained-release papaverine hydrochloride products in the form of microencapsulated pellets were evaluated. Three different dissolution apparatuses were used: a continuous flow apparatus, the USP rotating basket apparatus, and a modified reciprocating basket apparatus. The frequency rate of the reciprocating basket apparatus could be varied from 0 to 31 strokes/min. Salicylic acid compacts were used as a standard to characterize each apparatus. A linear log--log correlation between dissolution rate and apparatus speed or flow rate was obtained. Release of papaverine hydrochloride from the commercial preparations was affected significantly by the pH of the dissolution media but not by the agitation intensity."}
{"id": "PMID:25330", "title": "Prodrug approaches to enhancement of physicochemical properties of drugs IX: acetaminophen prodrug.", "content": "The synthesis, hydrolysis rate, and bioavailability of 1-(p-acetaminophenoxy)-1-ethoxyethane, an acetaminophen prodrug, are described. The prodrug is less soluble than acetaminophen and stable at neutral pH. However, in an acidic environment, the compound cleaves rapidly, generating acetaminophen. When both the prodrug and acetaminophen were administered to dogs in equivalent amounts, the blood acetaminophen levels were comparable.", "contents": "Prodrug approaches to enhancement of physicochemical properties of drugs IX: acetaminophen prodrug. The synthesis, hydrolysis rate, and bioavailability of 1-(p-acetaminophenoxy)-1-ethoxyethane, an acetaminophen prodrug, are described. The prodrug is less soluble than acetaminophen and stable at neutral pH. However, in an acidic environment, the compound cleaves rapidly, generating acetaminophen. When both the prodrug and acetaminophen were administered to dogs in equivalent amounts, the blood acetaminophen levels were comparable."}
{"id": "PMID:25331", "title": "Hydrolysis kinetics of the monophosphate ester triclofos sodium.", "content": "The hydrolysis kinetics of the monophosphate ester triclofos sodium were studied in the pH 0.00--7.80 range, the 80.1--98.4 degrees range, and ionic strengths of 0.02--1.50. The pK1 and pK2 values for triclofos were 1.00 +/- 0.05 and 5.80 +/- 0.05, respectively. The pH dependency observed was consistent with a theory in which the hydrolysis rates of the triclofos species follow the order: monoanion greater than unionized greater than dianion. The apparent first-order rate constants at 80.1 degrees associated with each species were 6.4 +/- 0.6 X 10(-3), 28.0 +/- 0.5 X 10(-3), and 0.3 +/- 0.1 hr-1, respectively, Different Arrhenius activation energies were observed at pH 0.00, 3.50, and 7.80, at which values the unionized, monoanion, and dianion forms were the dominant species present, respectively. The reaction showed a modest positive kinetic salt effect at pH 3.50 and a modest negative effect at pH 7.80. Various mechanistic possibilities are discussed.", "contents": "Hydrolysis kinetics of the monophosphate ester triclofos sodium. The hydrolysis kinetics of the monophosphate ester triclofos sodium were studied in the pH 0.00--7.80 range, the 80.1--98.4 degrees range, and ionic strengths of 0.02--1.50. The pK1 and pK2 values for triclofos were 1.00 +/- 0.05 and 5.80 +/- 0.05, respectively. The pH dependency observed was consistent with a theory in which the hydrolysis rates of the triclofos species follow the order: monoanion greater than unionized greater than dianion. The apparent first-order rate constants at 80.1 degrees associated with each species were 6.4 +/- 0.6 X 10(-3), 28.0 +/- 0.5 X 10(-3), and 0.3 +/- 0.1 hr-1, respectively, Different Arrhenius activation energies were observed at pH 0.00, 3.50, and 7.80, at which values the unionized, monoanion, and dianion forms were the dominant species present, respectively. The reaction showed a modest positive kinetic salt effect at pH 3.50 and a modest negative effect at pH 7.80. Various mechanistic possibilities are discussed."}
{"id": "PMID:25332", "title": "Determination of serum nadolol levels by GLC--selected ion monitoring mass spectrometry: comparison with a spectrofluorometric method.", "content": "A method to determine the serum concentration of the beta-adrenergic receptor blocking agent, nadolol, by GLC--selected ion monitoring mass spectrometry of the tri(trimethysilyl) ether derivative is described. A basic solution of serum was extracted, known amounts of internal standard were added to the extract, and the extract was back-extracted into acidic media and lyophilized. The resulting solids were reacted with N-trimethylsilylimidazole. Coded serum samples of 12 subjects, given nadolol alone or in combination with a second drug, were analyzed. The ions at m/e 86 and 100 were monitored to establish the relative concentration ratio of nadolol and the internal reference N-methylnadolol. No interferences from blood components or other administered drugs were observed. A detection level of 6.95 ng/ml of serum was found.", "contents": "Determination of serum nadolol levels by GLC--selected ion monitoring mass spectrometry: comparison with a spectrofluorometric method. A method to determine the serum concentration of the beta-adrenergic receptor blocking agent, nadolol, by GLC--selected ion monitoring mass spectrometry of the tri(trimethysilyl) ether derivative is described. A basic solution of serum was extracted, known amounts of internal standard were added to the extract, and the extract was back-extracted into acidic media and lyophilized. The resulting solids were reacted with N-trimethylsilylimidazole. Coded serum samples of 12 subjects, given nadolol alone or in combination with a second drug, were analyzed. The ions at m/e 86 and 100 were monitored to establish the relative concentration ratio of nadolol and the internal reference N-methylnadolol. No interferences from blood components or other administered drugs were observed. A detection level of 6.95 ng/ml of serum was found."}
{"id": "PMID:25333", "title": "Microionization constants of commercial cephalosporins.", "content": "The equilibrium constants of five commercial cephalosporins were determined. Two are monoacidic and possess one Ka while three are amphoteric and have four microconstants. Although several assumptions were made in the calculations, good agreement was found between the compounds and with previously reported macroionization constants. By utilizing the microionization constants, the ratios of zwitterion to unchanged species were calculated to be in the 900-50,000 range and to have a maximum concentration between pH 3.5 and 5.", "contents": "Microionization constants of commercial cephalosporins. The equilibrium constants of five commercial cephalosporins were determined. Two are monoacidic and possess one Ka while three are amphoteric and have four microconstants. Although several assumptions were made in the calculations, good agreement was found between the compounds and with previously reported macroionization constants. By utilizing the microionization constants, the ratios of zwitterion to unchanged species were calculated to be in the 900-50,000 range and to have a maximum concentration between pH 3.5 and 5."}
{"id": "PMID:25334", "title": "Pharmacokinetic studies on ditazole, a novel inhibitor of platelet aggregation.", "content": "The distribution of ditazole in blood and tissues of rats was determined by a simple GLC technique. Ditazole, after intravenous injection in rats (20 mg/kg), entered preferentially into the brain, the liver, and the heart in decreasing order. In the epididymal adipose tissue, the drug was present only in small amounts. Ditazole disappeared from the rat organs 4 hr after the treatment. The apparent ditazole half-life in rat blood was 41 min, the volume of distribution was 2.068 liters/kg, and the body clearance was 0.0345 liter/kg/min.", "contents": "Pharmacokinetic studies on ditazole, a novel inhibitor of platelet aggregation. The distribution of ditazole in blood and tissues of rats was determined by a simple GLC technique. Ditazole, after intravenous injection in rats (20 mg/kg), entered preferentially into the brain, the liver, and the heart in decreasing order. In the epididymal adipose tissue, the drug was present only in small amounts. Ditazole disappeared from the rat organs 4 hr after the treatment. The apparent ditazole half-life in rat blood was 41 min, the volume of distribution was 2.068 liters/kg, and the body clearance was 0.0345 liter/kg/min."}
{"id": "PMID:25335", "title": "Differential spectrophotometric determination of tyrosine and tryptophan in pharmaceutical amino acid solutions.", "content": "A method is proposed for the simultaneous determination of tyrosine and tryptophan in solutions by differential spectrophotometry. The concentrations are calculated from the measurement of the absorbance of the amino acid mixture in an alkaline medium and from the differential absorbance of the alkaline solution against the acid solution at 294.4 nm. A comparison with three other well-known methods is discussed.", "contents": "Differential spectrophotometric determination of tyrosine and tryptophan in pharmaceutical amino acid solutions. A method is proposed for the simultaneous determination of tyrosine and tryptophan in solutions by differential spectrophotometry. The concentrations are calculated from the measurement of the absorbance of the amino acid mixture in an alkaline medium and from the differential absorbance of the alkaline solution against the acid solution at 294.4 nm. A comparison with three other well-known methods is discussed."}
{"id": "PMID:25337", "title": "Rat jugular vein relaxes to norepinephrine, phenylephrine and histamine.", "content": "Circular muscle of the rat external jugular vein contracted to serotonin, angiotensin and potassium chloride but not to norepinephrine, phenylephrine, histamine or carbamylcholine. In contrast, rabbit and guinea-pig jugular veins contracted to norepinephrine, phenylephrine and histamine, although contractions to norepinephrine were small in guinea-pig jugular veins. Norepinephrine, phenylephrine and histamine produced a concentration-dependent sustained relaxation of serotonin-induced contractions in the rat jugular vein, as did isoproterenol, nitroglycerin and papaverine. Propranolol blocked relaxation to norepinephrine, phenylephrine and isoproterenol whereas metiamide, a H2 receptor antagonist blocked relaxation to histamine. alpha adrenergic receptor blockade with phentolamine or prazosin resulted in greater relaxation to norepinephrine whereas cocaine did not enhance norepinephrine-induced vasodilation. This study supports the premise that norepinephrine may exert prominent beta adrenergic receptor stimulation in some blood vessels and that this effect may be more apparent in veins than arteries.", "contents": "Rat jugular vein relaxes to norepinephrine, phenylephrine and histamine. Circular muscle of the rat external jugular vein contracted to serotonin, angiotensin and potassium chloride but not to norepinephrine, phenylephrine, histamine or carbamylcholine. In contrast, rabbit and guinea-pig jugular veins contracted to norepinephrine, phenylephrine and histamine, although contractions to norepinephrine were small in guinea-pig jugular veins. Norepinephrine, phenylephrine and histamine produced a concentration-dependent sustained relaxation of serotonin-induced contractions in the rat jugular vein, as did isoproterenol, nitroglycerin and papaverine. Propranolol blocked relaxation to norepinephrine, phenylephrine and isoproterenol whereas metiamide, a H2 receptor antagonist blocked relaxation to histamine. alpha adrenergic receptor blockade with phentolamine or prazosin resulted in greater relaxation to norepinephrine whereas cocaine did not enhance norepinephrine-induced vasodilation. This study supports the premise that norepinephrine may exert prominent beta adrenergic receptor stimulation in some blood vessels and that this effect may be more apparent in veins than arteries."}
{"id": "PMID:25341", "title": "Nucleoside transport in mammalian cell membranes. IV. Organomercurials and organomercurial-mercaptonucleoside complexes as probes for nucleoside transport systems in hamster cells.", "content": "Organomercurials form stable stoichiometric complexes with thiolated nucleosides. The complexes inhibited uptake of ribonucleosides and cytosine arabinoside (CAR) in various types of normal and transformed cells. The inhibition was competitive and reversible (Ki = 3--6 micrometer). The interaction between complexes and transport system displayed a 1:1 stoichiometry. Chemical factors which contributed to the inhibitory power were evaluated with a series of S-alkylated derivatives and S--Hg--R complexes of mercaptonucleosides. The inhibitory potency was not determined exclusively by the hydrophobic nature of either the S-alkylated or the S--Hg--R moieties. Chemical modification of cells with penetrating and nonpenetrating organomercurials lead to stimulation of nucleoside uptake and to an increase in its susceptibility to inhibition by S--Hg--R complexes or S-aklylated derivatives of mercaptopurine ribosides. The kinetic and chemical data obtained with nucleoside analogs and with chemical modifiers suggested complex features of nucleoside transport systems. Four distinct classes of sites were implied: (i) a substrate binding site susceptible directly to competitive inhibition by organomercurial-mercaptonucleoside complexes, (ii) an additional site susceptible either to S-arylalkylated or S-mercuriated derivatives of 6-mercaptopurine ribosides, (iii) SH-containing modifier sites which stimulate uridine uptake upon binding of organomercurials, and (iv) SH-containing modifier sites which inhibit the function upon binding of organomercurials. From the observation that only SH sites related to stimulation were susceptible to modification by macromolecular-SH modifier probes, some conclusions can be drawn regarding the disposition of the various sites in the cell membrane in general and among membrane components in particular.", "contents": "Nucleoside transport in mammalian cell membranes. IV. Organomercurials and organomercurial-mercaptonucleoside complexes as probes for nucleoside transport systems in hamster cells. Organomercurials form stable stoichiometric complexes with thiolated nucleosides. The complexes inhibited uptake of ribonucleosides and cytosine arabinoside (CAR) in various types of normal and transformed cells. The inhibition was competitive and reversible (Ki = 3--6 micrometer). The interaction between complexes and transport system displayed a 1:1 stoichiometry. Chemical factors which contributed to the inhibitory power were evaluated with a series of S-alkylated derivatives and S--Hg--R complexes of mercaptonucleosides. The inhibitory potency was not determined exclusively by the hydrophobic nature of either the S-alkylated or the S--Hg--R moieties. Chemical modification of cells with penetrating and nonpenetrating organomercurials lead to stimulation of nucleoside uptake and to an increase in its susceptibility to inhibition by S--Hg--R complexes or S-aklylated derivatives of mercaptopurine ribosides. The kinetic and chemical data obtained with nucleoside analogs and with chemical modifiers suggested complex features of nucleoside transport systems. Four distinct classes of sites were implied: (i) a substrate binding site susceptible directly to competitive inhibition by organomercurial-mercaptonucleoside complexes, (ii) an additional site susceptible either to S-arylalkylated or S-mercuriated derivatives of 6-mercaptopurine ribosides, (iii) SH-containing modifier sites which stimulate uridine uptake upon binding of organomercurials, and (iv) SH-containing modifier sites which inhibit the function upon binding of organomercurials. From the observation that only SH sites related to stimulation were susceptible to modification by macromolecular-SH modifier probes, some conclusions can be drawn regarding the disposition of the various sites in the cell membrane in general and among membrane components in particular."}
{"id": "PMID:25342", "title": "Hypertonic cryohemolysis: ionophore and pH effects.", "content": "Human erythrocytes suspended at 37 degrees C in hypertonic solution of either electrolytes or nonelectrolytes undergo hemolysis when the temperature is lowered toward 0 degrees C (Green, F.A., Jung, C.Y. 1977 J. Membrane Biol. 33:249). In the present studies this hypertonic cryohemolysis was profoundly affected by the pH of incubation, and was completely abolished at ph 5. In hypertonic NaCl, there was an apparent pH optimum at 6--6.5. In hypertonic sucrose, on the other hand, hemolysis increased progressively with increasing pH between 6 and 9. Amphotericin B inhibited hypertonic cryohemolysis in NaCl or KCl solution. No inhibiting effect of amphotericin B was observed when hypertonicity was due to sodium sulfate or sucrose. Valinomycin also inhibited hypertonic cryohemolysis in KCl, but did not affect the process in NaCl or sucrose solution. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate) and phloretin interfered with this valinomycin effect, whereas phlorizin did not. These results indicate that dissipation of an osmotic gradient across membranes may be responsible for the inhibition of the hemolysis by these inophores. Iso-osmotic cell shrinkage induced by valinomycin in 150 mM NaCl solution did not result in cryohemolysis.", "contents": "Hypertonic cryohemolysis: ionophore and pH effects. Human erythrocytes suspended at 37 degrees C in hypertonic solution of either electrolytes or nonelectrolytes undergo hemolysis when the temperature is lowered toward 0 degrees C (Green, F.A., Jung, C.Y. 1977 J. Membrane Biol. 33:249). In the present studies this hypertonic cryohemolysis was profoundly affected by the pH of incubation, and was completely abolished at ph 5. In hypertonic NaCl, there was an apparent pH optimum at 6--6.5. In hypertonic sucrose, on the other hand, hemolysis increased progressively with increasing pH between 6 and 9. Amphotericin B inhibited hypertonic cryohemolysis in NaCl or KCl solution. No inhibiting effect of amphotericin B was observed when hypertonicity was due to sodium sulfate or sucrose. Valinomycin also inhibited hypertonic cryohemolysis in KCl, but did not affect the process in NaCl or sucrose solution. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate) and phloretin interfered with this valinomycin effect, whereas phlorizin did not. These results indicate that dissipation of an osmotic gradient across membranes may be responsible for the inhibition of the hemolysis by these inophores. Iso-osmotic cell shrinkage induced by valinomycin in 150 mM NaCl solution did not result in cryohemolysis."}
{"id": "PMID:25343", "title": "Current-voltage relationships for the plasma membrane and its principal electrogenic pump in Neurospora crassa: I. Steady-state conditions.", "content": "The nonlinear membrane current-voltage relationship (I-V curve) for intact hyphae of Neurospora crassa has been determined by means of a 3-electrode voltage-clamp technique, plus \"quasi-linear\" cable theory. Under normal conditions of growth and respiration, the membrane I-V curve is best described as a parabolic segment convex in the direction of depolarizing current. At the average resting potential of - 174 mV, the membrane conductance is approximately 190 micronhos/cm2; conductance increase to approximately 240 micronhos/cm2 at -300 mV, and decreases to approximately 130 micronhos/cm2 at 0 mV. Irreversible membrane breakdown occurs at potentials beyond this range. Inhibition of the primary electrogenic pump in Neurospora by ATP withdrawal (with 1 mM KCN) depolarizes the membrane to the range of -40 to -70 mV and reduces the slope of the I-V curve by a fixed scaling factor of approximately 0.8. For wild-type Neurospora, compared under control conditions and during steady-state inhibition by cyanide, the I-V difference curve--presumed to define the current-voltage curve for the electrogenic pump--is a saturation function with maximal current of approximately 20 muA/cm2, a half saturation potential near -300 mV, and a projected reversal potential of ca. -400 mV. This value is close to the maximal free energy available to the pump from ATP hydrolysis, so that pump stoichiometry must be close to 1 H+ extruded:1 ATP split. The time-courses of change in membrane potential and resistance with cyanide are compatible with the steady-state I-V curves, under the assumption the cyanide has no major effects other than ATP withdrawal. Other inhibitors, uncouplers, and lowered temperature all have more complicated effects. The detailed temporal analysis of voltage-clamp data showed three time-constants in the clamping currents: one of 10 msec, for charging the membrane capacitance (0.9 muF/cm/2); a second of 50-75 msec; and a third of 20-30 sec, perhaps representing changes of intracellular composition.", "contents": "Current-voltage relationships for the plasma membrane and its principal electrogenic pump in Neurospora crassa: I. Steady-state conditions. The nonlinear membrane current-voltage relationship (I-V curve) for intact hyphae of Neurospora crassa has been determined by means of a 3-electrode voltage-clamp technique, plus \"quasi-linear\" cable theory. Under normal conditions of growth and respiration, the membrane I-V curve is best described as a parabolic segment convex in the direction of depolarizing current. At the average resting potential of - 174 mV, the membrane conductance is approximately 190 micronhos/cm2; conductance increase to approximately 240 micronhos/cm2 at -300 mV, and decreases to approximately 130 micronhos/cm2 at 0 mV. Irreversible membrane breakdown occurs at potentials beyond this range. Inhibition of the primary electrogenic pump in Neurospora by ATP withdrawal (with 1 mM KCN) depolarizes the membrane to the range of -40 to -70 mV and reduces the slope of the I-V curve by a fixed scaling factor of approximately 0.8. For wild-type Neurospora, compared under control conditions and during steady-state inhibition by cyanide, the I-V difference curve--presumed to define the current-voltage curve for the electrogenic pump--is a saturation function with maximal current of approximately 20 muA/cm2, a half saturation potential near -300 mV, and a projected reversal potential of ca. -400 mV. This value is close to the maximal free energy available to the pump from ATP hydrolysis, so that pump stoichiometry must be close to 1 H+ extruded:1 ATP split. The time-courses of change in membrane potential and resistance with cyanide are compatible with the steady-state I-V curves, under the assumption the cyanide has no major effects other than ATP withdrawal. Other inhibitors, uncouplers, and lowered temperature all have more complicated effects. The detailed temporal analysis of voltage-clamp data showed three time-constants in the clamping currents: one of 10 msec, for charging the membrane capacitance (0.9 muF/cm/2); a second of 50-75 msec; and a third of 20-30 sec, perhaps representing changes of intracellular composition."}
{"id": "PMID:25347", "title": "Bloody pericardial fluid. The value of blood gas measurements.", "content": "Clinically notable pericardial effusions developed in three patients with renal failure. Pericardiocentesis showed hemorrhagic fluid, the source of which was not apparent. Simultaneous determinations of PCO2, PO2, and pH values showed a substantial increase in PCO2 levels and decrease in PO2, pH, and bicarbonate levels in the pericardial compared with the intracardial aspirates. This was true when pericardial fluid PCO2, PO2, and pH values were compared with mixed venous samples. Determination of PO2, PCO2, pH, and bicarbonate values in pericardial aspirates may determine the source of the fluid.", "contents": "Bloody pericardial fluid. The value of blood gas measurements. Clinically notable pericardial effusions developed in three patients with renal failure. Pericardiocentesis showed hemorrhagic fluid, the source of which was not apparent. Simultaneous determinations of PCO2, PO2, and pH values showed a substantial increase in PCO2 levels and decrease in PO2, pH, and bicarbonate levels in the pericardial compared with the intracardial aspirates. This was true when pericardial fluid PCO2, PO2, and pH values were compared with mixed venous samples. Determination of PO2, PCO2, pH, and bicarbonate values in pericardial aspirates may determine the source of the fluid."}
{"id": "PMID:25348", "title": "Some new or poorly recognized physical and graphic findings in various forms of pericardial disease.", "content": "The eight new items concerning pericarditis (acute pericarditis, acute or chronic pericardial effusion, and constrictive or sero-constrictive pericarditis) were demonstrated based on the clinical observation of 115 patients. Pericarditis, a disease of remote antiquity, still has many fascinating and unrecognized aspects, which will be uncovered by the meticulous observation of the patients.", "contents": "Some new or poorly recognized physical and graphic findings in various forms of pericardial disease. The eight new items concerning pericarditis (acute pericarditis, acute or chronic pericardial effusion, and constrictive or sero-constrictive pericarditis) were demonstrated based on the clinical observation of 115 patients. Pericarditis, a disease of remote antiquity, still has many fascinating and unrecognized aspects, which will be uncovered by the meticulous observation of the patients."}
{"id": "PMID:25351", "title": "[Use of beta-adrenergic blockaders in the treatment of arterial hypertension].", "content": "The results of treatment of over 300 patients suffering from hypertensive disease with beta-blocking agents Obsidan and Visken are analysed and the place of these agents among other hypotensive drugs is discussed. The therapeutic effect was most evident in patients with the early stages of the disease and hyperkinetic type of circulation. The daily doses were from 60 to 240 mg. The hemodynamic shifts were displayed by a decrease in the cardiac output and rate of cardiac contractions and reflex, ususlly moderate, increase in general peripheral resistance, as a result the arterial pressure decreased gradually. In 1 to 6 months general peripheral resistance diminished in half of the patients, evidently due to the gradual adaptation of the vascular tone to the chronic reduction of the cardiac output. Treatment with beta-blocking agents led to non-uniform changes in regional hemodynamics: the tone of the cerebral arteries significantly reduced, the tone of the arteries of the lower extremities had a tendency to increase. This gives rise to the conclusion that alpha-adrenergic receptors predominate in the vessels of the lower extremities. In the treatment of patients with high and stable hypertension, it is advisable to combine beta-blocking agents with saluretics, vasodilators, hemiton, and other hypotensive drugs.", "contents": "[Use of beta-adrenergic blockaders in the treatment of arterial hypertension]. The results of treatment of over 300 patients suffering from hypertensive disease with beta-blocking agents Obsidan and Visken are analysed and the place of these agents among other hypotensive drugs is discussed. The therapeutic effect was most evident in patients with the early stages of the disease and hyperkinetic type of circulation. The daily doses were from 60 to 240 mg. The hemodynamic shifts were displayed by a decrease in the cardiac output and rate of cardiac contractions and reflex, ususlly moderate, increase in general peripheral resistance, as a result the arterial pressure decreased gradually. In 1 to 6 months general peripheral resistance diminished in half of the patients, evidently due to the gradual adaptation of the vascular tone to the chronic reduction of the cardiac output. Treatment with beta-blocking agents led to non-uniform changes in regional hemodynamics: the tone of the cerebral arteries significantly reduced, the tone of the arteries of the lower extremities had a tendency to increase. This gives rise to the conclusion that alpha-adrenergic receptors predominate in the vessels of the lower extremities. In the treatment of patients with high and stable hypertension, it is advisable to combine beta-blocking agents with saluretics, vasodilators, hemiton, and other hypotensive drugs."}
{"id": "PMID:25352", "title": "[Coronary circulation under alpha-adrenergic blockade].", "content": "In canine experiments with coronary catheterization and perfusion, catheterization of the heart cavities and great vessles, and with thermodilution it was demonstrated that the alpha-adrenergic blocker Phentolamine causes a regular flow resistance in the coronary vessels. The maximal depressor effect was observed with 0.3 mg/kg (intravenously), and it did not grow under higher doses of the drug. The reduction of coronary resistance under the effect of Phentolamine was realized, firstly, by way of a moderate activation of myocardial beta-receptors, and secondly, by way of a specific block of alpha-adrenergic receptors of the heart vessels. Phentolamine inhibited the pressor reactions of the coronaries to mesatone, adrenalin, noradrenalin, and limited the manifestations of the pressor effects in the coronary vessels during systemic sinocarotid reflexes.", "contents": "[Coronary circulation under alpha-adrenergic blockade]. In canine experiments with coronary catheterization and perfusion, catheterization of the heart cavities and great vessles, and with thermodilution it was demonstrated that the alpha-adrenergic blocker Phentolamine causes a regular flow resistance in the coronary vessels. The maximal depressor effect was observed with 0.3 mg/kg (intravenously), and it did not grow under higher doses of the drug. The reduction of coronary resistance under the effect of Phentolamine was realized, firstly, by way of a moderate activation of myocardial beta-receptors, and secondly, by way of a specific block of alpha-adrenergic receptors of the heart vessels. Phentolamine inhibited the pressor reactions of the coronaries to mesatone, adrenalin, noradrenalin, and limited the manifestations of the pressor effects in the coronary vessels during systemic sinocarotid reflexes."}
{"id": "PMID:25355", "title": "[The different effects of fe(II)- and fe(III)-ions on the hyaluronic acid of the vitreous body (author's transl)].", "content": "Fe(II)-ions reduce the viscosity of a hyaluronic acid solution but do not form a precipitate. Fe(III)-ions only slightly lower the viscosity of hyaluronic acid solutions but cause a brown, water-insoluble iron-hyaluronic acid precipitate. After adding ascorbic acid--concentrate the pH-value as in vitreous body--to the reaction solution, Fe(III)-ions reduce the viscosity too. The iron-hyalurnic acid complex is also destroyed by ascorbate. Therefore, the ascorbate of the vitreous humor plays an important role in the generation of siderosis bulbi.", "contents": "[The different effects of fe(II)- and fe(III)-ions on the hyaluronic acid of the vitreous body (author's transl)]. Fe(II)-ions reduce the viscosity of a hyaluronic acid solution but do not form a precipitate. Fe(III)-ions only slightly lower the viscosity of hyaluronic acid solutions but cause a brown, water-insoluble iron-hyaluronic acid precipitate. After adding ascorbic acid--concentrate the pH-value as in vitreous body--to the reaction solution, Fe(III)-ions reduce the viscosity too. The iron-hyalurnic acid complex is also destroyed by ascorbate. Therefore, the ascorbate of the vitreous humor plays an important role in the generation of siderosis bulbi."}
{"id": "PMID:25356", "title": "[Possibility of conserving the heat balance of the human organism in an extremely rarefied atmosphere by vacuum evaporation of sweat from the surface of the body].", "content": "As a result of 64 experiments carried out on 24 test subjects, it has been shown that extreme overwarming due to moderate and heavy thermal loads can be prevented with the aid of heat release through sweat evaporation from the surface of the body under the action of a rarefied atmosphere (termed vacuum sweat evaporation). The test subjects wearing altitude suits remained in a thermal altitude chamber at 40 and 55 degrees C for 8 to 3 hours at rest and doing light work at altitudes of 7 to 25 km without marked signs of overwarming. The entire heat release occurred only through vacuum sweat evaporation from the surface of the body that was under the altitude suit during a gradual decrease of the chamber pressure to 20 mm Hg (equivalent to an altitude of 25 km). The findings give support to the hypothesis that heart release via vacuum sweat evaporation from the surface of the body can be used as a method of controlling thermal homeostasis during high altitude and space flights.", "contents": "[Possibility of conserving the heat balance of the human organism in an extremely rarefied atmosphere by vacuum evaporation of sweat from the surface of the body]. As a result of 64 experiments carried out on 24 test subjects, it has been shown that extreme overwarming due to moderate and heavy thermal loads can be prevented with the aid of heat release through sweat evaporation from the surface of the body under the action of a rarefied atmosphere (termed vacuum sweat evaporation). The test subjects wearing altitude suits remained in a thermal altitude chamber at 40 and 55 degrees C for 8 to 3 hours at rest and doing light work at altitudes of 7 to 25 km without marked signs of overwarming. The entire heat release occurred only through vacuum sweat evaporation from the surface of the body that was under the altitude suit during a gradual decrease of the chamber pressure to 20 mm Hg (equivalent to an altitude of 25 km). The findings give support to the hypothesis that heart release via vacuum sweat evaporation from the surface of the body can be used as a method of controlling thermal homeostasis during high altitude and space flights."}
{"id": "PMID:25357", "title": "[Experimental substantiation of the maximum permissible concentrations of acetone and acetaldehyde in regenerated drinking water].", "content": "The paper presents experimental data indicating maximum permissible concentrations of acetone and acetaldehyde in reclaimed potable water used for different periods of time--up to 1, 3 or 12 months. The recommended concentrations for reclaimed water used for a year are 14.0 mg/l and 0.2 mg/l for acetone and acetaldehyde, respectively. The recommended levels for reclaimed water used for 1--3 months are 39.6 mg/l and 0.2 mg/l for acetone and acetaldehyde, respectively.", "contents": "[Experimental substantiation of the maximum permissible concentrations of acetone and acetaldehyde in regenerated drinking water]. The paper presents experimental data indicating maximum permissible concentrations of acetone and acetaldehyde in reclaimed potable water used for different periods of time--up to 1, 3 or 12 months. The recommended concentrations for reclaimed water used for a year are 14.0 mg/l and 0.2 mg/l for acetone and acetaldehyde, respectively. The recommended levels for reclaimed water used for 1--3 months are 39.6 mg/l and 0.2 mg/l for acetone and acetaldehyde, respectively."}
{"id": "PMID:25361", "title": "Submandibular salivary pH as a diagnostic aid for prognosis of facial palsy.", "content": "The present paper aims at introducing a new method of testing the function of the chorda tympani with the aid of submandibular salivary pH. This method has several advantages: (1.) it enables the measurement of the function of only the paralyzed side; (2.) it accurately predicts the outcome of facial palsy at an early stage; and (3.) the method is simple and inexpensive.", "contents": "Submandibular salivary pH as a diagnostic aid for prognosis of facial palsy. The present paper aims at introducing a new method of testing the function of the chorda tympani with the aid of submandibular salivary pH. This method has several advantages: (1.) it enables the measurement of the function of only the paralyzed side; (2.) it accurately predicts the outcome of facial palsy at an early stage; and (3.) the method is simple and inexpensive."}
{"id": "PMID:25368", "title": "[Effect of soap and detergents on the restitution of acidity and lipids of the skin surface].", "content": "A comparative evaluation of the effects of soaps and detergents on pH behaviour and lipids level on the skin surface and duration of their restitution was carried out. The studies were conducted in two groups. The first group of 32 persons used 1% solution of \"BHP\" soap, whereas the other one, composed of 31 persons, 0,5% solution of detergentpowder \"POLLENA\". PH measurements of skin were performed using pH--meter of Radelkis firm with a combined glass and calomel electrode. Lipids on the skin surface were determined by the Hodgson--Jones and Wheatly's gravimetric method. The evaluation of soap and detergent's effects on skin was based on the mean output and direct pH values of the skin surface, accidental and residual level of lipids, and comparison of the duration of these parameters restitution. The soap was found to alkalyse stronger than the detergent, and duration of pH restitution is longer after using the soap, whereas the detergent degreases the skin more intensively than the soap. Also restitution of lipid's jacket is slower after using the detergent.", "contents": "[Effect of soap and detergents on the restitution of acidity and lipids of the skin surface]. A comparative evaluation of the effects of soaps and detergents on pH behaviour and lipids level on the skin surface and duration of their restitution was carried out. The studies were conducted in two groups. The first group of 32 persons used 1% solution of \"BHP\" soap, whereas the other one, composed of 31 persons, 0,5% solution of detergentpowder \"POLLENA\". PH measurements of skin were performed using pH--meter of Radelkis firm with a combined glass and calomel electrode. Lipids on the skin surface were determined by the Hodgson--Jones and Wheatly's gravimetric method. The evaluation of soap and detergent's effects on skin was based on the mean output and direct pH values of the skin surface, accidental and residual level of lipids, and comparison of the duration of these parameters restitution. The soap was found to alkalyse stronger than the detergent, and duration of pH restitution is longer after using the soap, whereas the detergent degreases the skin more intensively than the soap. Also restitution of lipid's jacket is slower after using the detergent."}
{"id": "PMID:25369", "title": "An affinity-column procedure for the purification of veratrate O-demethylase from fungi.", "content": "An affinity column procedure is reported for purifying veratrate O-demethylase from higher fungi. The procedure is based on the affinity of the fungal demethylases for veratrate, which was coupled to AH-Sepharose 4B. An over 300-fold purification of the enzyme from an Ascomycete (Chaetomium piluliferum), and a lower degree of purification (20-fold) from a Basidiomycete (Xerocomus badius), were obtained. The O-demethylases from higher fungi require NADH and oxygen. The enzyme activity is sensitive to exposure to oxygen. The pH optima are 5 for enzyme from Chaetomium, and 7 for demethylase from Xerocomus, respectively. The enzymes are not specific for veratrate. They also demethylate p- and m-anisate and 3,4-dimethoxycinnamate, but to a lower degree.", "contents": "An affinity-column procedure for the purification of veratrate O-demethylase from fungi. An affinity column procedure is reported for purifying veratrate O-demethylase from higher fungi. The procedure is based on the affinity of the fungal demethylases for veratrate, which was coupled to AH-Sepharose 4B. An over 300-fold purification of the enzyme from an Ascomycete (Chaetomium piluliferum), and a lower degree of purification (20-fold) from a Basidiomycete (Xerocomus badius), were obtained. The O-demethylases from higher fungi require NADH and oxygen. The enzyme activity is sensitive to exposure to oxygen. The pH optima are 5 for enzyme from Chaetomium, and 7 for demethylase from Xerocomus, respectively. The enzymes are not specific for veratrate. They also demethylate p- and m-anisate and 3,4-dimethoxycinnamate, but to a lower degree."}
{"id": "PMID:25370", "title": "Specific agglutination of Escherichia coli O128B12 by the mannose-binding proteins of Pseudomonas aeruginosa.", "content": "The mannosephilic haemagglutinins of Pseudomonas aeruginosa were found to agglutinate cells of Escherichia coli O128B12, to be adsorbed onto them and to attach peroxidase to them. These reactions were specifically inhibited by D-mannose. No agglutination by this Pseudomonas haemagglutinin was obtained when several other enteropathogenic types of Escherichia coli and some other Gram-negative bacteria were examined. Concanavalin A, which also reacted with Escherichia coli O128B12 cells, interacted with some of the other bacteria examined, too. Escherichia coli O128B12 was not agglutinated by the Pseudomonas galactosephilic haemagglutinins and those of the plant Phaseolus vulgaris. Its maximal agglutination by the Pseudomonas mannosephilic haemagglutinins was obtained employing cells grown for 4-6 h in conventional media. The growth temperature, aeration and presence of certain amino acids, but not D-mannose, in the culture medium had some effect on the agglutination in tensity; pH 6-8 was optimal for it and only at pH 3.0-3.2 no agglutination was observed. Treatment of the bacteria by proteolytic enzymes, ethanol or formaldehyde did not alter their agglutinability by either the Pseudomonas lectin or by antibodies produced against them in rabbits. Heating of the bacteria to 100 degrees C prevented their agglutination by the Pseudomonas lectin and lowered their ability to adsorb it, but did not significantly affect their reactions with the rabbit antibodies.", "contents": "Specific agglutination of Escherichia coli O128B12 by the mannose-binding proteins of Pseudomonas aeruginosa. The mannosephilic haemagglutinins of Pseudomonas aeruginosa were found to agglutinate cells of Escherichia coli O128B12, to be adsorbed onto them and to attach peroxidase to them. These reactions were specifically inhibited by D-mannose. No agglutination by this Pseudomonas haemagglutinin was obtained when several other enteropathogenic types of Escherichia coli and some other Gram-negative bacteria were examined. Concanavalin A, which also reacted with Escherichia coli O128B12 cells, interacted with some of the other bacteria examined, too. Escherichia coli O128B12 was not agglutinated by the Pseudomonas galactosephilic haemagglutinins and those of the plant Phaseolus vulgaris. Its maximal agglutination by the Pseudomonas mannosephilic haemagglutinins was obtained employing cells grown for 4-6 h in conventional media. The growth temperature, aeration and presence of certain amino acids, but not D-mannose, in the culture medium had some effect on the agglutination in tensity; pH 6-8 was optimal for it and only at pH 3.0-3.2 no agglutination was observed. Treatment of the bacteria by proteolytic enzymes, ethanol or formaldehyde did not alter their agglutinability by either the Pseudomonas lectin or by antibodies produced against them in rabbits. Heating of the bacteria to 100 degrees C prevented their agglutination by the Pseudomonas lectin and lowered their ability to adsorb it, but did not significantly affect their reactions with the rabbit antibodies."}
{"id": "PMID:25373", "title": "[X-ray examination of the abdomen in hypnotic-sedative drug poisoning--casuistical contribution (author's transl)].", "content": "By means of an impressive example the significance of abdominal X-ray examination in cases of intoxication with hypnotic-sedative drugs is pointed out. Apart from the qualitative diagnosis (drug containing bromide) the radiological proof of shadow-giving substances also permits a quantitative clinical assessment and has prognostical as well as therapeutical consequences.", "contents": "[X-ray examination of the abdomen in hypnotic-sedative drug poisoning--casuistical contribution (author's transl)]. By means of an impressive example the significance of abdominal X-ray examination in cases of intoxication with hypnotic-sedative drugs is pointed out. Apart from the qualitative diagnosis (drug containing bromide) the radiological proof of shadow-giving substances also permits a quantitative clinical assessment and has prognostical as well as therapeutical consequences."}
{"id": "PMID:25372", "title": "A solution to the graft-versus-host problem in bone marrow transplantation to humans.", "content": "Many clinical situations arise where it would be desirable to transplant bone marrow to a marrow function deficient patient. However, bone marrow is immunologically competent by virtue of its content of lymphocyte precursors. Marrow transplantation in these patients is followed by the graft's immunological rejection of the patient - a fatal disease. A system for specific abrogation of this graft-versus-host disease after xenogeneic bone marrow transplantation to humans is presented. In this system, prospective patient cells are removed by skin biopsy for example, and injected into a fetal chimpanzee. The fetal chimpanzee becomes tolerant to this patient's antigens and will not attack or reject them when its bone marrow is removed after birth and injected into the specific patient from whom the tolerogenic cells were obtained. A simple and straightforward experimental test of this system's clinical applicability is also presented.", "contents": "A solution to the graft-versus-host problem in bone marrow transplantation to humans. Many clinical situations arise where it would be desirable to transplant bone marrow to a marrow function deficient patient. However, bone marrow is immunologically competent by virtue of its content of lymphocyte precursors. Marrow transplantation in these patients is followed by the graft's immunological rejection of the patient - a fatal disease. A system for specific abrogation of this graft-versus-host disease after xenogeneic bone marrow transplantation to humans is presented. In this system, prospective patient cells are removed by skin biopsy for example, and injected into a fetal chimpanzee. The fetal chimpanzee becomes tolerant to this patient's antigens and will not attack or reject them when its bone marrow is removed after birth and injected into the specific patient from whom the tolerogenic cells were obtained. A simple and straightforward experimental test of this system's clinical applicability is also presented."}
{"id": "PMID:25379", "title": "Release of [14C]tyrosine from tubulinyl-[14C]tyrosine by brain extract. Separation of a carboxypeptidase from tubulin-tyrosine ligase.", "content": "The carboxypeptidase previously described that releases tyrosine from tubulinyl-tyrosine was obtained from rat brain preparation free of tubulin-tyrosine ligase. The enzyme was purified 24-fold. Its activity was increased by 2 mM MgCl2 or 30 mM KCl. Mercaptoethanol (50 mM), colchicine (0.2 mM) and tyrosine (0.2 mM) showed practically no effect on the release of tyrosine whereas iodoacetate (2 mM), deoxycholate (0.5%), CuCl2 (0.1 mM), ZnCl2 (0.1 mM) and NaCl or KCl (240 mM) had a strong inhibitory effect. The optimal pH of this enzyme was 6.3--7. A preparation containing tubulin-tyrosine ligase free of carboxypeptidase was also obtained. This preparation catalyzed the release of tyrosine from tyrosinated tubulin in the presence of ADP, Mg2+, K+ and Pi and the incorporation of tyrosine into tubulin. For the releasing activity the optimal concentration of MgCl2 was 3--20 mM and of KCl was 10--30 mM. For ADP the maximal act;vity was at 0.3 mM or higher. An important difference between the activities of the carboxypeptidase and the ligase was that the former was active on denatured tubulin whereas the latter was not.", "contents": "Release of [14C]tyrosine from tubulinyl-[14C]tyrosine by brain extract. Separation of a carboxypeptidase from tubulin-tyrosine ligase. The carboxypeptidase previously described that releases tyrosine from tubulinyl-tyrosine was obtained from rat brain preparation free of tubulin-tyrosine ligase. The enzyme was purified 24-fold. Its activity was increased by 2 mM MgCl2 or 30 mM KCl. Mercaptoethanol (50 mM), colchicine (0.2 mM) and tyrosine (0.2 mM) showed practically no effect on the release of tyrosine whereas iodoacetate (2 mM), deoxycholate (0.5%), CuCl2 (0.1 mM), ZnCl2 (0.1 mM) and NaCl or KCl (240 mM) had a strong inhibitory effect. The optimal pH of this enzyme was 6.3--7. A preparation containing tubulin-tyrosine ligase free of carboxypeptidase was also obtained. This preparation catalyzed the release of tyrosine from tyrosinated tubulin in the presence of ADP, Mg2+, K+ and Pi and the incorporation of tyrosine into tubulin. For the releasing activity the optimal concentration of MgCl2 was 3--20 mM and of KCl was 10--30 mM. For ADP the maximal act;vity was at 0.3 mM or higher. An important difference between the activities of the carboxypeptidase and the ligase was that the former was active on denatured tubulin whereas the latter was not."}
{"id": "PMID:25380", "title": "Reversible inhibition of cyclic AMP-dependent protein kinase by insulin.", "content": "Extracts of fasted rat diaphragms, previously treated with or without insulin were assayed for glycogen synthase, protein kinase and cyclic [3H]-AMP binding. Treatment with insulin produced an elevation in the % of glycogen synthase I and a concurrent decrease in cyclic AMP-dependent protein kinase activity and cyclic [3H]-AMP binding. Analysis of extracts by disc gel electrophoresis demonstrated the inhibition of cyclic [3H]-AMP binding to involve the Type I protein kinase holoenzyme. Inhibition of protein kinase activity was most apparent in the presence of 0.2 micrometer cyclic AMP, with enzymatic activity of the insulin-treated extracts typically 60--65% of control. Higher assay concentrations diminished the difference between control and insulin-treated extracts and concentrations greater than 20 micrometer abolished it. The inhibition of cyclic AMP-dependent protein kinase activity after insulin was a transient and labile phenomenon. The effect was independent of ATP concentration in the assay, but was sensitive to the pH of tissue extraction, requiring a pH of 7.0 to 8.4 to be observed. Insulin-mediated inhibition of protein kinase activity was reversed upon preincubation of extracts at 0--2 degrees. Relatively concentrated homogenates (less than 4 microliter buffer/mg tissue) yielded extracts which exhibited little or no inhibition of protein kinase activity compared to extracts prepared from more dilute (6--10 microliter/mg) homogenates. A model for the inhibition of the cyclic-AMP dependent protein kinase by an insulin-generated inhibitor which becomes directly associated with the Type 1 holoenzyme is proposed.", "contents": "Reversible inhibition of cyclic AMP-dependent protein kinase by insulin. Extracts of fasted rat diaphragms, previously treated with or without insulin were assayed for glycogen synthase, protein kinase and cyclic [3H]-AMP binding. Treatment with insulin produced an elevation in the % of glycogen synthase I and a concurrent decrease in cyclic AMP-dependent protein kinase activity and cyclic [3H]-AMP binding. Analysis of extracts by disc gel electrophoresis demonstrated the inhibition of cyclic [3H]-AMP binding to involve the Type I protein kinase holoenzyme. Inhibition of protein kinase activity was most apparent in the presence of 0.2 micrometer cyclic AMP, with enzymatic activity of the insulin-treated extracts typically 60--65% of control. Higher assay concentrations diminished the difference between control and insulin-treated extracts and concentrations greater than 20 micrometer abolished it. The inhibition of cyclic AMP-dependent protein kinase activity after insulin was a transient and labile phenomenon. The effect was independent of ATP concentration in the assay, but was sensitive to the pH of tissue extraction, requiring a pH of 7.0 to 8.4 to be observed. Insulin-mediated inhibition of protein kinase activity was reversed upon preincubation of extracts at 0--2 degrees. Relatively concentrated homogenates (less than 4 microliter buffer/mg tissue) yielded extracts which exhibited little or no inhibition of protein kinase activity compared to extracts prepared from more dilute (6--10 microliter/mg) homogenates. A model for the inhibition of the cyclic-AMP dependent protein kinase by an insulin-generated inhibitor which becomes directly associated with the Type 1 holoenzyme is proposed."}
{"id": "PMID:25384", "title": "Antacid titration in the prevention of acute gastrointestinal bleeding: a controlled, randomized trial in 100 critically ill patients.", "content": "We randomized 100 critically ill patients at risk of developing acute gastrointestinal ulceration and bleeding into two groups. One (51 patients) received antacid prophylaxis, and the other (49 patients) received no specific form of prophylaxis. Hourly antacid titration kept the pH of the gastric contents above 3.5. Two of the 51 patients who received antacid prophylaxis and gastrointestinal bleeding. Twelve of the 49 control patients bled (P less than 0.005). Of the 12 patients in the control group who bled, seven were placed on antacid medication, and all seven apparently stopped bleeding. Analysis of all the patients showed that an increasing prevalence of respiratory, failure, sepsis, peritonitis, jaundice, renal failure and hypotension was correlated with a greater frequency of bleeding. No patients required operative treatment to control bleeding. These data indicate that the occurrence of acute gastrointestinal bleeding in critically ill patients can be reduced by antacid titration.", "contents": "Antacid titration in the prevention of acute gastrointestinal bleeding: a controlled, randomized trial in 100 critically ill patients. We randomized 100 critically ill patients at risk of developing acute gastrointestinal ulceration and bleeding into two groups. One (51 patients) received antacid prophylaxis, and the other (49 patients) received no specific form of prophylaxis. Hourly antacid titration kept the pH of the gastric contents above 3.5. Two of the 51 patients who received antacid prophylaxis and gastrointestinal bleeding. Twelve of the 49 control patients bled (P less than 0.005). Of the 12 patients in the control group who bled, seven were placed on antacid medication, and all seven apparently stopped bleeding. Analysis of all the patients showed that an increasing prevalence of respiratory, failure, sepsis, peritonitis, jaundice, renal failure and hypotension was correlated with a greater frequency of bleeding. No patients required operative treatment to control bleeding. These data indicate that the occurrence of acute gastrointestinal bleeding in critically ill patients can be reduced by antacid titration."}
{"id": "PMID:25385", "title": "A manpower policy for primary health care.", "content": "A National Academy of Sciences study of policy options for the supply of primary health-care manpower has produced a comprehensive set of recommendations. The study finds an adequate overall supply of physicians, but a shortage of primary health-care practitioners. It recommends maintaining current enrollment levels in medical schools and training programs for nurse practitioners and physician assistants and increasing the proportion of primary-care residents. To enhance the availability of primary care, the report advocates reimbursement for all physicians within a state at the same payment level for the same primary-care service, a reduction in payment differentials between primary-care services and nonprimary-care services, and reimbursement for educational and preventive services and for new health-practitioner services. The report supports a team approach in primary-care training and recommends that all medical students obtain clinical experience in a primary-care setting and some instruction in epidemiology and behavioral and social sciences.", "contents": "A manpower policy for primary health care. A National Academy of Sciences study of policy options for the supply of primary health-care manpower has produced a comprehensive set of recommendations. The study finds an adequate overall supply of physicians, but a shortage of primary health-care practitioners. It recommends maintaining current enrollment levels in medical schools and training programs for nurse practitioners and physician assistants and increasing the proportion of primary-care residents. To enhance the availability of primary care, the report advocates reimbursement for all physicians within a state at the same payment level for the same primary-care service, a reduction in payment differentials between primary-care services and nonprimary-care services, and reimbursement for educational and preventive services and for new health-practitioner services. The report supports a team approach in primary-care training and recommends that all medical students obtain clinical experience in a primary-care setting and some instruction in epidemiology and behavioral and social sciences."}
{"id": "PMID:25387", "title": "The structure of the flavoenzyme glutathione reductase.", "content": "The three-dimensional structure of the dimeric flavoenzyme glutathione reductase from human erythrocytes has been elucidated by an X-ray diffraction analysis at 0.3 nm resolution. The polypeptide chain has been traced, and the binding positions of FAD, NADP and glutathione have been determined. A mechanism for the electron transfer is discussed.", "contents": "The structure of the flavoenzyme glutathione reductase. The three-dimensional structure of the dimeric flavoenzyme glutathione reductase from human erythrocytes has been elucidated by an X-ray diffraction analysis at 0.3 nm resolution. The polypeptide chain has been traced, and the binding positions of FAD, NADP and glutathione have been determined. A mechanism for the electron transfer is discussed."}
{"id": "PMID:25400", "title": "[Effect of antimediator preparations on the intercellular relations in early embryos of the sea urchin].", "content": "The dated treatment of the early embryos of an irregular (flat) sea urchin Scaphechinus mirabilis by neuropharmacological drugs (anti-neurotransmitters) during one of the first four cleavage divisions results in the impairment of intercellular connections and leads to the formation of twin embryos, dwarf embryos, embryos of the dumb-bell shape etc. In the experiments with some of the drugs under study such developmental abnormalities were not seen or were expressed much more weakly when serotonin or bufotenin (N,N-dimethylserotonin) were added to the medium. A suggestion is put forward that the early embryos possess an intracellular mechanism participating in the interaction between the cells and operating via endogenous monoamines, primarily serotonin.", "contents": "[Effect of antimediator preparations on the intercellular relations in early embryos of the sea urchin]. The dated treatment of the early embryos of an irregular (flat) sea urchin Scaphechinus mirabilis by neuropharmacological drugs (anti-neurotransmitters) during one of the first four cleavage divisions results in the impairment of intercellular connections and leads to the formation of twin embryos, dwarf embryos, embryos of the dumb-bell shape etc. In the experiments with some of the drugs under study such developmental abnormalities were not seen or were expressed much more weakly when serotonin or bufotenin (N,N-dimethylserotonin) were added to the medium. A suggestion is put forward that the early embryos possess an intracellular mechanism participating in the interaction between the cells and operating via endogenous monoamines, primarily serotonin."}
{"id": "PMID:25401", "title": "[Effect of cortisol administration and stress actions in early ontogeny on hormonal induction in adult rats].", "content": "The influence of cortisole injections and stress (\"handling\") in the early ontogenesis (during the first 9 or 16 days of life) on the process of thyrosine aminotransferase induction by cortisol in the adult rats has been studied. It was shown that both the injection of the hormone in the young rats and \"handling\" led to the manifested trace effects: (1) stable increase of thyrosine aminotransferase activity in the liver of adult (5-6 months) rats and (2) appearance of peculiar tolerance to cortisol in the form of decrease in the ability of cells to induce thyrosine aminotransferase in response to the hormone injection. The data obtained suggest that the sensitive period of postnatal ontogenesis when cortisol or \"handling\" exert such a stable effect is limited by the 3rd and 9th days after birth. The causes of such \"biochemical imprinting\" are considered with respect to the increased sensitivity of the genetical system of cells-targets to the transcription inducers during the early postnatal development.", "contents": "[Effect of cortisol administration and stress actions in early ontogeny on hormonal induction in adult rats]. The influence of cortisole injections and stress (\"handling\") in the early ontogenesis (during the first 9 or 16 days of life) on the process of thyrosine aminotransferase induction by cortisol in the adult rats has been studied. It was shown that both the injection of the hormone in the young rats and \"handling\" led to the manifested trace effects: (1) stable increase of thyrosine aminotransferase activity in the liver of adult (5-6 months) rats and (2) appearance of peculiar tolerance to cortisol in the form of decrease in the ability of cells to induce thyrosine aminotransferase in response to the hormone injection. The data obtained suggest that the sensitive period of postnatal ontogenesis when cortisol or \"handling\" exert such a stable effect is limited by the 3rd and 9th days after birth. The causes of such \"biochemical imprinting\" are considered with respect to the increased sensitivity of the genetical system of cells-targets to the transcription inducers during the early postnatal development."}
{"id": "PMID:25407", "title": "Cystic fibrosis: isolation and physical properties of a salivary cystic fibrosis factor.", "content": "A ciliostatic factor has been isolated from cystic fibrosis (CF) saliva by dialyzing it from purified alpha-amylase prepared by a glycogen-complex method. This method of isolating the CF factor is an improvement over the previously employed heparin procedure. The activity of the isolated factor is proportional with concentration using the oyster gill ciliostatic assay and in its inhibition of mammalian glycogen debranching enzyme. The ciliostatic action of the factor can be reversed by heparin under certain conditions. The type of inhibition of the debranching enzyme by the isolated CF factor indicates that its chemical structure is similar to that observed with hydroxyalkylamines and polyamine metabolites. Physical properties of the isolated factor indicate that it is of low molecular weight and is labile as a function of pH and temperature. At neutral pH the conditions under which it is maintained have a direct effect on the length of time that it is stable.", "contents": "Cystic fibrosis: isolation and physical properties of a salivary cystic fibrosis factor. A ciliostatic factor has been isolated from cystic fibrosis (CF) saliva by dialyzing it from purified alpha-amylase prepared by a glycogen-complex method. This method of isolating the CF factor is an improvement over the previously employed heparin procedure. The activity of the isolated factor is proportional with concentration using the oyster gill ciliostatic assay and in its inhibition of mammalian glycogen debranching enzyme. The ciliostatic action of the factor can be reversed by heparin under certain conditions. The type of inhibition of the debranching enzyme by the isolated CF factor indicates that its chemical structure is similar to that observed with hydroxyalkylamines and polyamine metabolites. Physical properties of the isolated factor indicate that it is of low molecular weight and is labile as a function of pH and temperature. At neutral pH the conditions under which it is maintained have a direct effect on the length of time that it is stable."}
{"id": "PMID:25410", "title": "Immunologic studies of arylsulfatase A in normal and metachromatic leukodystrophy liver.", "content": "Purified human liver arylsulfatase A on polyacrylamide gel electrophoresis at pH 4.0 is separated into two protein forms with enzymatic activity and two distinct inactive subunits. All of these components were immunologically distinguishable using different antisera preparations. In late infantile metachromatic leukodystrophy, only one of the two inactive subunits was immunologically detected, whereas in the juvenile form of metachromatic leukodystrophy, both inactive subunits were antigenically present.", "contents": "Immunologic studies of arylsulfatase A in normal and metachromatic leukodystrophy liver. Purified human liver arylsulfatase A on polyacrylamide gel electrophoresis at pH 4.0 is separated into two protein forms with enzymatic activity and two distinct inactive subunits. All of these components were immunologically distinguishable using different antisera preparations. In late infantile metachromatic leukodystrophy, only one of the two inactive subunits was immunologically detected, whereas in the juvenile form of metachromatic leukodystrophy, both inactive subunits were antigenically present."}
{"id": "PMID:25411", "title": "Hypophosphatemic vitamin D-resistant rickets: metabolic balance studies in a child receiving 1,25 dihydroxyvitamin D3, phosphate, and ascorbic acid.", "content": "A child with hypophosphatemic vitamin D-resistant rickets was treated for three years with the conventional vitamin D-inorganic phosphate supplementation followed by a new therapeutic regimen consisting of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) and half of the previous phosphate supplementation. The effectiveness of the two treatment regimens was compared by calcium, phosphate, and magnesium balance techniques and by serial radiological examinations as well as careful height measurements. In addition, the lowering of the urinary pH with ascorbic acid supplementation seems to be associated with improvement in the renal tubular reabsorption of phosphate, but its distinct effect, separate from the rest of the treatment modalities, was not tested in this study. The conventional treatment did not correct the hypophosphatemia and alkaline phosphatase elevation, whereas the 1,25 (OH)2 D3-inorganic phosphate regimen is well tolerated and effective in achieving a sustained normalization of these variables. In addition, the improved growth and healing of rickets further attest to the efficacy of the new treatment.", "contents": "Hypophosphatemic vitamin D-resistant rickets: metabolic balance studies in a child receiving 1,25 dihydroxyvitamin D3, phosphate, and ascorbic acid. A child with hypophosphatemic vitamin D-resistant rickets was treated for three years with the conventional vitamin D-inorganic phosphate supplementation followed by a new therapeutic regimen consisting of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) and half of the previous phosphate supplementation. The effectiveness of the two treatment regimens was compared by calcium, phosphate, and magnesium balance techniques and by serial radiological examinations as well as careful height measurements. In addition, the lowering of the urinary pH with ascorbic acid supplementation seems to be associated with improvement in the renal tubular reabsorption of phosphate, but its distinct effect, separate from the rest of the treatment modalities, was not tested in this study. The conventional treatment did not correct the hypophosphatemia and alkaline phosphatase elevation, whereas the 1,25 (OH)2 D3-inorganic phosphate regimen is well tolerated and effective in achieving a sustained normalization of these variables. In addition, the improved growth and healing of rickets further attest to the efficacy of the new treatment."}
{"id": "PMID:25412", "title": "Arterial blood gases in Pranayama practice.", "content": "Pranayama is a Yogic breathing practice which is known experientially to produce a profound calming effect on the mind. In an experiment designed to determine whether the mental effects of this practice were accompanied by changes in the arterial blood gases, arterial blood was drawn from 10 trained individuals prior to and immediately after Pranayama practice. No significance changes in arterial blood gases were noted after Pranayama. A neural mechanism for the mental effects of this practice is proposed.", "contents": "Arterial blood gases in Pranayama practice. Pranayama is a Yogic breathing practice which is known experientially to produce a profound calming effect on the mind. In an experiment designed to determine whether the mental effects of this practice were accompanied by changes in the arterial blood gases, arterial blood was drawn from 10 trained individuals prior to and immediately after Pranayama practice. No significance changes in arterial blood gases were noted after Pranayama. A neural mechanism for the mental effects of this practice is proposed."}
{"id": "PMID:25413", "title": "[Giant cell arteritis and takayasu's disease: histopathological criteria (author's transl)].", "content": "Both of these arterial diseases may involve the aorta and the major arterial trunks. Two cases of subclavian involvement are used to contrast them from a histopathological standpoint. In giant cell arteritis, the lesions affect above all the internal elastic layer and the inner part of the media, destroyed by an inflammatory infiltrate with giant cells. In Takayasu's disease, the lesions involve the adventitia, the site of fibrosis and of inflammatory islets with the vasa vasorum at the centres. Involvement of the media is predominantly in its outer part, the internal elastic layer being intact. A histopathological definition of these arterial diseases may be envisaged on the basis of these facts.", "contents": "[Giant cell arteritis and takayasu's disease: histopathological criteria (author's transl)]. Both of these arterial diseases may involve the aorta and the major arterial trunks. Two cases of subclavian involvement are used to contrast them from a histopathological standpoint. In giant cell arteritis, the lesions affect above all the internal elastic layer and the inner part of the media, destroyed by an inflammatory infiltrate with giant cells. In Takayasu's disease, the lesions involve the adventitia, the site of fibrosis and of inflammatory islets with the vasa vasorum at the centres. Involvement of the media is predominantly in its outer part, the internal elastic layer being intact. A histopathological definition of these arterial diseases may be envisaged on the basis of these facts."}
{"id": "PMID:25414", "title": "Preparative separation of the complementary strands of DNA restriction fragments by alkaline RPC-5 chromatography.", "content": "High pressure reversed phase chromatography (RPC-5) at pH 12 was used for preparative separation of the complementary strands of the smaller DNA fragments which are generated by the Hae III restriction endonuclease digestion of Col El DNA. A single high pressure RPC-5 chromatographic step at neutral pH served to purify duplex fragments 70, 172, 250 and 440 base pairs long; each of these yielded two elution peaks upon chromatography under alkaline denaturing conditions.", "contents": "Preparative separation of the complementary strands of DNA restriction fragments by alkaline RPC-5 chromatography. High pressure reversed phase chromatography (RPC-5) at pH 12 was used for preparative separation of the complementary strands of the smaller DNA fragments which are generated by the Hae III restriction endonuclease digestion of Col El DNA. A single high pressure RPC-5 chromatographic step at neutral pH served to purify duplex fragments 70, 172, 250 and 440 base pairs long; each of these yielded two elution peaks upon chromatography under alkaline denaturing conditions."}
{"id": "PMID:25415", "title": "Turbidimetric and potentiometric studies of ribosomal subunits from an erythromycin resistant mutant of Escherichia coli.", "content": "Turbidimetric and potentiometric techniques were applied to the analysis of an EryR mutant. Results show that in the mutant, the 30S subunits are drastically altered, as indicated by a higher Mg2+ requirement for subunit association and by an important difference in the titratable groups. Replacement of parental 50S by mutant 50S subunits does not decrease the association capacity with 30S parental subunits, but a structural difference is detected in the mutant 50S with potentiometric measurements. The mutation results in decreased ribosomal in vitro activities at 22 degrees C including lowered polyphenylalanine synthesis, drastic altered initiation step and the loss of erythromycin binding to the ribosomes. The results extend previous observation of a gene eryC part in the maturation of both subunits.", "contents": "Turbidimetric and potentiometric studies of ribosomal subunits from an erythromycin resistant mutant of Escherichia coli. Turbidimetric and potentiometric techniques were applied to the analysis of an EryR mutant. Results show that in the mutant, the 30S subunits are drastically altered, as indicated by a higher Mg2+ requirement for subunit association and by an important difference in the titratable groups. Replacement of parental 50S by mutant 50S subunits does not decrease the association capacity with 30S parental subunits, but a structural difference is detected in the mutant 50S with potentiometric measurements. The mutation results in decreased ribosomal in vitro activities at 22 degrees C including lowered polyphenylalanine synthesis, drastic altered initiation step and the loss of erythromycin binding to the ribosomes. The results extend previous observation of a gene eryC part in the maturation of both subunits."}
{"id": "PMID:25416", "title": "Affinity adsorbents consisting of nucleic acids immobilized via bisoxirane activated polysaccharides.", "content": "An easy and efficient procedure for the immobilization of polynucleotide ligands to bisoxirane activated insoluble polysaccharides has been elaborated and is described in this paper. The resulting materials have been applied to the chromatography of DNA polymerase I, and RNA polymerase from E.coli. Because of their extraordinary stability to temperature, formamide, and alkaline conditions they seem to be particularly useful adsorbents for nucleic acid hybridization.", "contents": "Affinity adsorbents consisting of nucleic acids immobilized via bisoxirane activated polysaccharides. An easy and efficient procedure for the immobilization of polynucleotide ligands to bisoxirane activated insoluble polysaccharides has been elaborated and is described in this paper. The resulting materials have been applied to the chromatography of DNA polymerase I, and RNA polymerase from E.coli. Because of their extraordinary stability to temperature, formamide, and alkaline conditions they seem to be particularly useful adsorbents for nucleic acid hybridization."}
{"id": "PMID:25417", "title": "Sequence analysis of 5'[32P] labeled mRNA and tRNA using polyacrylamide gel electrophoresis.", "content": "Sequence analysis of 5'-[32P] labeled tRNA and eukaryotic mRNA using an adaptation of a method recently described by Donis-Keller, Maxam and Gilbert for mapping guanines, adenines and pyrimidines from the 5'-end of an RNA is described. In addition, a technique utilizing two-dimensional polyacrylamide gel electrophoresis for identification of pyrimidines within a sequence is described. 5'-[32P] Labeled rabbit beta-globin mRNA and N. crassa mitochondrial initiator tRNA were partially digested with T1- RNase for cleavage at G residues, with U2-RNase for cleavage at A residues, with an extracellular RNase from B. cereus for cleavage at pyrimidine residues and with T2-RNase or with alkali for cleavage at all four residues. The 5'-[32P] labeled partial digestion products were separated according to their size, by electrophoresis in adjacent lanes of a polyacrylamide slab gel and the location of G's, A's and of pyrimidines extending 60-80 nucleotides from the 5'-end of the RNA determined. Two-dimensional polyacrylamide gel electrophoresis was used to separate the 5'-[32P] labeled fragments present in partial alkali digests of a 5'-[32P] labeled mRNA. The mobility shifts corresponding to the difference of a C residue were distinct from those corresponding to a U residue and this formed the basis of a method for distinguishing between the pyrimidines.", "contents": "Sequence analysis of 5'[32P] labeled mRNA and tRNA using polyacrylamide gel electrophoresis. Sequence analysis of 5'-[32P] labeled tRNA and eukaryotic mRNA using an adaptation of a method recently described by Donis-Keller, Maxam and Gilbert for mapping guanines, adenines and pyrimidines from the 5'-end of an RNA is described. In addition, a technique utilizing two-dimensional polyacrylamide gel electrophoresis for identification of pyrimidines within a sequence is described. 5'-[32P] Labeled rabbit beta-globin mRNA and N. crassa mitochondrial initiator tRNA were partially digested with T1- RNase for cleavage at G residues, with U2-RNase for cleavage at A residues, with an extracellular RNase from B. cereus for cleavage at pyrimidine residues and with T2-RNase or with alkali for cleavage at all four residues. The 5'-[32P] labeled partial digestion products were separated according to their size, by electrophoresis in adjacent lanes of a polyacrylamide slab gel and the location of G's, A's and of pyrimidines extending 60-80 nucleotides from the 5'-end of the RNA determined. Two-dimensional polyacrylamide gel electrophoresis was used to separate the 5'-[32P] labeled fragments present in partial alkali digests of a 5'-[32P] labeled mRNA. The mobility shifts corresponding to the difference of a C residue were distinct from those corresponding to a U residue and this formed the basis of a method for distinguishing between the pyrimidines."}
{"id": "PMID:25418", "title": "Poly(dG).poly(dC) at neutral and alkaline pH: the formation of triple stranded poly(dG).poly(dG).poly(dC).", "content": "Alkaline titrations of different samples of poly(dG).poly(dC) and of the constituent homopolymers poly(dG) and poly(dC) have been performed in 0.15 M NaCl and their CD spectra followed. Sample I contained a slight excess of poly(dC) (52% C: 48% G) and showed a single reversible transition (pK = 11.9) due to the dissociation of double stranded poly(dG).poly(dC). Sample II, containing an excess of poly(dG) (43% C: 57% G), showed two transitions (pK1 = 11.4, PK2 = 11.9) the first one being only partially reversible. Examination of the CD spectra along the alkaline titrations indicated the presence of another hydrogen-bonded complex of higher G content. Mixing curves performed at pH 8 have confirmed the presence of a 2G: 1C complex, besides the double stranded complex. It can be formed in amounts up to 30% by mixing the two homopolymers, alkali treatment and heating. The CD spectra of the two complexes have been computed from the CD data of the mixing curves. This permitted the determination of the concentrations of both complexes and homopolymers in all samples. The ratio of triple to double stranded complex is not only dependent on the G/C ratio of the sample, but also a function of the previous physico-chemical conditions. These results explain the variability of many properties of different poly(dG).poly(dC) samples observed by other workers.", "contents": "Poly(dG).poly(dC) at neutral and alkaline pH: the formation of triple stranded poly(dG).poly(dG).poly(dC). Alkaline titrations of different samples of poly(dG).poly(dC) and of the constituent homopolymers poly(dG) and poly(dC) have been performed in 0.15 M NaCl and their CD spectra followed. Sample I contained a slight excess of poly(dC) (52% C: 48% G) and showed a single reversible transition (pK = 11.9) due to the dissociation of double stranded poly(dG).poly(dC). Sample II, containing an excess of poly(dG) (43% C: 57% G), showed two transitions (pK1 = 11.4, PK2 = 11.9) the first one being only partially reversible. Examination of the CD spectra along the alkaline titrations indicated the presence of another hydrogen-bonded complex of higher G content. Mixing curves performed at pH 8 have confirmed the presence of a 2G: 1C complex, besides the double stranded complex. It can be formed in amounts up to 30% by mixing the two homopolymers, alkali treatment and heating. The CD spectra of the two complexes have been computed from the CD data of the mixing curves. This permitted the determination of the concentrations of both complexes and homopolymers in all samples. The ratio of triple to double stranded complex is not only dependent on the G/C ratio of the sample, but also a function of the previous physico-chemical conditions. These results explain the variability of many properties of different poly(dG).poly(dC) samples observed by other workers."}
{"id": "PMID:25419", "title": "Base specific fractionation of double stranded DNA: affinity chromatography on a novel type of adsorbant.", "content": "A material suitable for base-pair-specific \"affinity chromatography\" of double stranded DNA is described. The synthesis of this material involves two successive polymerization reactions yielding solid particles of cross-linked bisacrylamide to which base-pair-specific dyes are covalently attached by spacers of polyacrylamide chains of different length. Materials with immobilized A.T-specific malachite green or G.C-specific phenyl neutral red were used for base-pair-specific fractionation of sheared DNA from bacterial sources, as well as of higher molecular weight Calf thymus DNA or defined fragments of coliphage lambda DNA. The excellent resolving power of this method of \"affinity chromatography\" of nucleic acids is comparable only to DNA fractionation in buoyant density gradients in the presence of base-pair-specific ligands. A great advantage of this material is its simple handling and its chemical stability, which allows repeated re-use of the same column.", "contents": "Base specific fractionation of double stranded DNA: affinity chromatography on a novel type of adsorbant. A material suitable for base-pair-specific \"affinity chromatography\" of double stranded DNA is described. The synthesis of this material involves two successive polymerization reactions yielding solid particles of cross-linked bisacrylamide to which base-pair-specific dyes are covalently attached by spacers of polyacrylamide chains of different length. Materials with immobilized A.T-specific malachite green or G.C-specific phenyl neutral red were used for base-pair-specific fractionation of sheared DNA from bacterial sources, as well as of higher molecular weight Calf thymus DNA or defined fragments of coliphage lambda DNA. The excellent resolving power of this method of \"affinity chromatography\" of nucleic acids is comparable only to DNA fractionation in buoyant density gradients in the presence of base-pair-specific ligands. A great advantage of this material is its simple handling and its chemical stability, which allows repeated re-use of the same column."}
{"id": "PMID:25420", "title": "New observations concerning the chloroacetaldehyde reaction with some tRNA constituents. Stable intermediates, kinetics and selectivity of the reaction.", "content": "The stable intermediates formed in the reaction of cytosine, cytidine and adenosine with chloracetaldehyde were isolated. The -CH2CH/OH/- bridge between the exo and endo nitrogen atoms of the parent base was found in these compounds by means of PMR spectroscopy. Their acid-induced dehydration resulted in formation of appropriate ethenoderivatives. The rate constants of the intermediate formation and its dehydration were found to be 38x10(-4) and 47x10(-4) /min-1/ for adenosine, and 33x10(-4) and 10x10(-4) /min-1/ for cytidine. The PH range of 4.5--5.0 was found to be optimum for both adenosine and cytidine reactions. The quantitative modification of these two nucleosides in the presence of guanosine may be achieved with high selectivity only at a low pH of 3.0--4.0 N6-methyladenosine and N4-methylcytidine react quantitatively with chloroacetaldehyde and the reaction rate is higher than in the case of the parent nucleosides. The structure of the reaction products was assigned on the basis of PMR spectroscopy.", "contents": "New observations concerning the chloroacetaldehyde reaction with some tRNA constituents. Stable intermediates, kinetics and selectivity of the reaction. The stable intermediates formed in the reaction of cytosine, cytidine and adenosine with chloracetaldehyde were isolated. The -CH2CH/OH/- bridge between the exo and endo nitrogen atoms of the parent base was found in these compounds by means of PMR spectroscopy. Their acid-induced dehydration resulted in formation of appropriate ethenoderivatives. The rate constants of the intermediate formation and its dehydration were found to be 38x10(-4) and 47x10(-4) /min-1/ for adenosine, and 33x10(-4) and 10x10(-4) /min-1/ for cytidine. The PH range of 4.5--5.0 was found to be optimum for both adenosine and cytidine reactions. The quantitative modification of these two nucleosides in the presence of guanosine may be achieved with high selectivity only at a low pH of 3.0--4.0 N6-methyladenosine and N4-methylcytidine react quantitatively with chloroacetaldehyde and the reaction rate is higher than in the case of the parent nucleosides. The structure of the reaction products was assigned on the basis of PMR spectroscopy."}
{"id": "PMID:25421", "title": "Evidence that proteins S1, S11 and S21 directly participates in the binding of transfer RNA to the 30S ribosome.", "content": "In a previous publication1 we reported that the tyrosine selective reagent, tetraitromethane, causes complete inactivation of E. coli 30S ribosomes for poly U directed non-enzymatic phe-tRNA binding. This inactivation was demonstrated to be due to the chemical modification of the protein moiety of the ribosome. We have no identified the proteins of the 30S particle inactivated by this modification. Using a method of ribosome reconstruction we have found that unmodified proteins S1, S11, and S21 are essential for the restoration of the phe-tRNA binding activity of tetranitromethane inactivated ribosomes. We propose that these three proteins are intimately involved in the 30S ribosome binding site for tRNA.", "contents": "Evidence that proteins S1, S11 and S21 directly participates in the binding of transfer RNA to the 30S ribosome. In a previous publication1 we reported that the tyrosine selective reagent, tetraitromethane, causes complete inactivation of E. coli 30S ribosomes for poly U directed non-enzymatic phe-tRNA binding. This inactivation was demonstrated to be due to the chemical modification of the protein moiety of the ribosome. We have no identified the proteins of the 30S particle inactivated by this modification. Using a method of ribosome reconstruction we have found that unmodified proteins S1, S11, and S21 are essential for the restoration of the phe-tRNA binding activity of tetranitromethane inactivated ribosomes. We propose that these three proteins are intimately involved in the 30S ribosome binding site for tRNA."}
{"id": "PMID:25424", "title": "Physico-chemical investigation of AlPO4 for the manufacture of antacids. I. Effect of precipitation and processing conditions on physico-chemical properties of AlPO4.", "content": "Aluminium phosphate was precipitated from AlCl3-H3PO4 and NaOH, NH3H2O and NaHCO3--Na2CO3 mixture up to different pH values. The precipitates were dried at room temperature, 40 degrees and 105 degrees and their neutralizing properties (rate of neutralization and acid-consuming capacity) against 0.l N HCl were investigated. It was found that these properties depend on the nature of the reagents used for the formation of AlPO4, the pH and also the temperature of drying. The best antacid properties shows the AlPO4 preperation obtained from AlCl3-H3PO4 and NaHCO3-Na2CO3. For comparison, the therapeutic preparate \"Aluphos\" was also investigated.", "contents": "Physico-chemical investigation of AlPO4 for the manufacture of antacids. I. Effect of precipitation and processing conditions on physico-chemical properties of AlPO4. Aluminium phosphate was precipitated from AlCl3-H3PO4 and NaOH, NH3H2O and NaHCO3--Na2CO3 mixture up to different pH values. The precipitates were dried at room temperature, 40 degrees and 105 degrees and their neutralizing properties (rate of neutralization and acid-consuming capacity) against 0.l N HCl were investigated. It was found that these properties depend on the nature of the reagents used for the formation of AlPO4, the pH and also the temperature of drying. The best antacid properties shows the AlPO4 preperation obtained from AlCl3-H3PO4 and NaHCO3-Na2CO3. For comparison, the therapeutic preparate \"Aluphos\" was also investigated."}
{"id": "PMID:25427", "title": "[Mendelson's syndrome].", "content": "Mendelson's syndrome is discussed with a review of the literature and presentation of 27 personal cases studies. Accidental aspiration of gastric fluid occurs primarily during anesthesia, in cranial trauma victims, and in toxic coma patients. Tissue damage is proportional to the acidity and the quantity of aspirated fluid. The initial clinical manifestations are often serious, sometimes leading to acute respiratory distress syndrom with pulmonary edema. Frequent infectious complications, often with anaerobic microbes, are deciding factors in the prognosis. Artificial ventilation with positive pressure (sometimes continuous) is often necessary. Administration of corticosteroids at high doses is likely favorable. Prophylactic administration of antibiotics is initially directed against anaerobic agents. The prevention of this serious syndrome should be a primary concern of anesthesiologists and physicians treating comatous patients.", "contents": "[Mendelson's syndrome]. Mendelson's syndrome is discussed with a review of the literature and presentation of 27 personal cases studies. Accidental aspiration of gastric fluid occurs primarily during anesthesia, in cranial trauma victims, and in toxic coma patients. Tissue damage is proportional to the acidity and the quantity of aspirated fluid. The initial clinical manifestations are often serious, sometimes leading to acute respiratory distress syndrom with pulmonary edema. Frequent infectious complications, often with anaerobic microbes, are deciding factors in the prognosis. Artificial ventilation with positive pressure (sometimes continuous) is often necessary. Administration of corticosteroids at high doses is likely favorable. Prophylactic administration of antibiotics is initially directed against anaerobic agents. The prevention of this serious syndrome should be a primary concern of anesthesiologists and physicians treating comatous patients."}
{"id": "PMID:25425", "title": "Choline acetyltransferase and acetylcholinesterase activities in mice brain during the antagonistic action of antidepressant drugs and Ro 4--1284.", "content": "Choline acetyltransferase (Ach-T) and acetylcholinesterase (Ach-E) activities in mice brain during the reverse action by imipramine, pheniprazine and pargyline to the syndrome elicited by intraperitoneal administration of Ro 4--1284 were investigated. A single dose of imipramine did not reverse reserpine-like syndrome whereas inhibited Ach-E activity and increased Ach-T activity at the same time. The reversal of reserpine-like syndrome by administration of pargyline, pheniprazine or chronic administration of imipramine was accompanied by no changes in Ach-E and Ach-T activities.", "contents": "Choline acetyltransferase and acetylcholinesterase activities in mice brain during the antagonistic action of antidepressant drugs and Ro 4--1284. Choline acetyltransferase (Ach-T) and acetylcholinesterase (Ach-E) activities in mice brain during the reverse action by imipramine, pheniprazine and pargyline to the syndrome elicited by intraperitoneal administration of Ro 4--1284 were investigated. A single dose of imipramine did not reverse reserpine-like syndrome whereas inhibited Ach-E activity and increased Ach-T activity at the same time. The reversal of reserpine-like syndrome by administration of pargyline, pheniprazine or chronic administration of imipramine was accompanied by no changes in Ach-E and Ach-T activities."}
{"id": "PMID:25426", "title": "Central action of narcotic analgesics. II. Locomotor activity and narcotic analgesics.", "content": "The effect of morphine, codeine, fentanyl and pentazocine on locomotor activity of rats and mice and open-field performance of rats were tested. All the analgesics tested produced a depressive action in the rat. In mice a depressive action was produced by pentazocine and codeine. Fentanyl increased the exploratory and basal locomotor activity of mice. Morphine increased the exploratory activity, but, given at doses of 2.5 and 10 mg/kg decreased the basal locomotor activity. The increase of locomotor activity in mice by morphine and fentanyl is caused by an indirect stimulation of catecholamine receptors.", "contents": "Central action of narcotic analgesics. II. Locomotor activity and narcotic analgesics. The effect of morphine, codeine, fentanyl and pentazocine on locomotor activity of rats and mice and open-field performance of rats were tested. All the analgesics tested produced a depressive action in the rat. In mice a depressive action was produced by pentazocine and codeine. Fentanyl increased the exploratory and basal locomotor activity of mice. Morphine increased the exploratory activity, but, given at doses of 2.5 and 10 mg/kg decreased the basal locomotor activity. The increase of locomotor activity in mice by morphine and fentanyl is caused by an indirect stimulation of catecholamine receptors."}
{"id": "PMID:25429", "title": "[Preventive action of catecholamine and serotonin synthesis inhibitors and of adrenergic blockaders on the occurrence of the anovular syndrome in neonatally androgenized rats. I].", "content": "Administration of catecholamine synthesis inhibitors (alpha-methl-p-tyrosine) or serotonin (parachlorphenylalanine) simultaneously with testosterone propionate prevented the anovular sterility in the majority of the neonatally androgenized rats. Preventive action of adrenoblockers (droperidol and propranolol) on the effects of early androgenization were weak. The data obtained pointed to the participation of catecholamines and serotonin in the realization of the masculinizing action of androgen on the neuroendocrine centres of the gonadotropin hormones secretion control.", "contents": "[Preventive action of catecholamine and serotonin synthesis inhibitors and of adrenergic blockaders on the occurrence of the anovular syndrome in neonatally androgenized rats. I]. Administration of catecholamine synthesis inhibitors (alpha-methl-p-tyrosine) or serotonin (parachlorphenylalanine) simultaneously with testosterone propionate prevented the anovular sterility in the majority of the neonatally androgenized rats. Preventive action of adrenoblockers (droperidol and propranolol) on the effects of early androgenization were weak. The data obtained pointed to the participation of catecholamines and serotonin in the realization of the masculinizing action of androgen on the neuroendocrine centres of the gonadotropin hormones secretion control."}
{"id": "PMID:25436", "title": "Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides.", "content": "Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport.", "contents": "Regulation of Ca2+ release from mitochondria by the oxidation-reduction state of pyridine nucleotides. Mitochondria from normal rat liver and heart, and also Ehrlich tumor cells, respiring on succinate as energy source in the presence of rotenone (to prevent net electron flow to oxygen from the endogenous pyridine nucleotides), rapidly take up Ca(2+) and retain it so long as the pyridine nucleotides are kept in the reduced state. When acetoacetate is added to bring the pyridine nucleotides into a more oxidized state, Ca(2+) is released to the medium. A subsequent addition of a reductant of the pyridine nucleotides such as beta-hydroxybutyrate, glutamate, or isocitrate causes reuptake of the released Ca(2+). Successive cycles of Ca(2+) release and uptake can be induced by shifting the redox state of the pyridine nucleotides to more oxidized and more reduced states, respectively. Similar observations were made when succinate oxidation was replaced as energy source by ascorbate oxidation or by the hydrolysis of ATP. These and other observations form the basis of a hypothesis for feedback regulation of Ca(2+)-dependent substrate- or energy-mobilizing enzymatic reactions by the uptake or release of mitochondrial Ca(2+), mediated by the cytosolic phosphate potential and the ATP-dependent reduction of mitochondrial pyridine nucleotides by reversal of electron transport."}
{"id": "PMID:25437", "title": "Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine.", "content": "Two methyltransferases involved in the methylation of phosphatidylethanolamine to form phosphatidylcholine were demonstrated in a microsomal fraction of bovine adrenal medulla. The first methyltransferase catalyzes the methylation of phosphatidylethanolamine to form phosphatidyl-N-monomethylethanolamine. This enzyme has an optimum pH of 6.5, a low Km for S-adenosyl-L-methionine (1.4 micron), and an absolute requirement for Mg2+. The second methyltransferase catalyzes the two successive methylations of phodphatidyl-N-monomethylethanolamine to phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. In contrast to the first methyltransferase, it has an optimum pH of 10 and a high Km for S-adenosyl-L-methionine (0.1 mM) and does not require Mg2+.", "contents": "Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. Two methyltransferases involved in the methylation of phosphatidylethanolamine to form phosphatidylcholine were demonstrated in a microsomal fraction of bovine adrenal medulla. The first methyltransferase catalyzes the methylation of phosphatidylethanolamine to form phosphatidyl-N-monomethylethanolamine. This enzyme has an optimum pH of 6.5, a low Km for S-adenosyl-L-methionine (1.4 micron), and an absolute requirement for Mg2+. The second methyltransferase catalyzes the two successive methylations of phodphatidyl-N-monomethylethanolamine to phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. In contrast to the first methyltransferase, it has an optimum pH of 10 and a high Km for S-adenosyl-L-methionine (0.1 mM) and does not require Mg2+."}
{"id": "PMID:25438", "title": "Differences in the isoelectric focusing patterns of gamma-glutamyl transpeptidase from normal and cancerous rat mammary tissue.", "content": "Highly purified fractions of gamma-glutamyl transpeptidase [gamma-glutamyltrinsferase; (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2] from normal and malignant rat mammary tissue were prepared. Analyses by isoelectric focusing indicate the existence of at least 12 enzymatically active species. The gamma-glutamyl transpeptidase from the tumor tissue had a greater proportion of the activity concentrated in the more negative species than the enzyme from normal tissue. Treatment of the two enzyme preparations with neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) greatly reduced this difference. When whole tissue homogenates were treated with papain to solubilize the enzyme and then focused, the same relationship held. The neuraminidase activities in the two homogenates were similar, but the sialytransferase activity (CMP-N-acetylneuraminate:D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) of the tumor homogenate was 13 times that of the normal mammary homogenate. These observations suggest that the gamma-glutamyl transpeptidase of the tumor is more heavily sialylated than that from the normal tissue, possibly reflecting the greater sialyltransferase activity of the tumor.", "contents": "Differences in the isoelectric focusing patterns of gamma-glutamyl transpeptidase from normal and cancerous rat mammary tissue. Highly purified fractions of gamma-glutamyl transpeptidase [gamma-glutamyltrinsferase; (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2] from normal and malignant rat mammary tissue were prepared. Analyses by isoelectric focusing indicate the existence of at least 12 enzymatically active species. The gamma-glutamyl transpeptidase from the tumor tissue had a greater proportion of the activity concentrated in the more negative species than the enzyme from normal tissue. Treatment of the two enzyme preparations with neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) greatly reduced this difference. When whole tissue homogenates were treated with papain to solubilize the enzyme and then focused, the same relationship held. The neuraminidase activities in the two homogenates were similar, but the sialytransferase activity (CMP-N-acetylneuraminate:D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) of the tumor homogenate was 13 times that of the normal mammary homogenate. These observations suggest that the gamma-glutamyl transpeptidase of the tumor is more heavily sialylated than that from the normal tissue, possibly reflecting the greater sialyltransferase activity of the tumor."}
{"id": "PMID:25439", "title": "High-resolution 31P nuclear magnetic resonance study of rat liver mitochondria.", "content": "Intact mitochondria were studied by high-resolution 31P nuclear magnetic resonance. Observable internal phosphate compounds included inorganic phosphate (Pi), ADP, and ATP. The internal pH was determined by the chemical shift of the internal Pi, the pK2 (6.7) of which was measured in uncoupled mitochondria. The observed equilibrium relation between the internal and the external Pi was consistent with the exchange equilibrium through the H2PO4-/OH- carrier. The internal ATP and ADP were essentially Mg2+ bound and their resonances were distinguishable from those of the external ATP and ADP by the chemical shift differences due to the Mg2+ concentration gradient and deltapH. Oxidative phosphorylation was followed by the separate resonances of Pi and adenine nucleotides both internal and external to mitochondria. From these resonances the internal and external phosphate potentials could be estimated.", "contents": "High-resolution 31P nuclear magnetic resonance study of rat liver mitochondria. Intact mitochondria were studied by high-resolution 31P nuclear magnetic resonance. Observable internal phosphate compounds included inorganic phosphate (Pi), ADP, and ATP. The internal pH was determined by the chemical shift of the internal Pi, the pK2 (6.7) of which was measured in uncoupled mitochondria. The observed equilibrium relation between the internal and the external Pi was consistent with the exchange equilibrium through the H2PO4-/OH- carrier. The internal ATP and ADP were essentially Mg2+ bound and their resonances were distinguishable from those of the external ATP and ADP by the chemical shift differences due to the Mg2+ concentration gradient and deltapH. Oxidative phosphorylation was followed by the separate resonances of Pi and adenine nucleotides both internal and external to mitochondria. From these resonances the internal and external phosphate potentials could be estimated."}
{"id": "PMID:25440", "title": "Differential desensitization of functional adrenergic receptors in normal and malignant myeloid cells: relationship to receptor-mediated hormone cytotoxicity.", "content": "Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells have beta(2)-adrenergic receptors, and the [(3)H]dihydroalprenolol binding was saturable, reversible, and stereospecific. The leukemic cells consisted of clones that could be induced to differentiate (MGI(+)D(+)) and clones that could not be induced to differentiate to mature macrophages and granulocytes by the protein inducer MGI. The different types of leukemic clones all had 1100-2300 receptor sites per cell, whereas normal macrophages had 7000 receptors per cell. The differentiation of MGI(+)D(+) leukemic cells was associated with an increase in receptors to a number similar to that found with normal macrophages. MGI(+)D(+) leukemic cells and normal macrophages were able to densensitize to the beta-adrenergic agonist (-)isoproterenol, shown by termination of cyclic AMP induction within 10-15 min and the lack of a second induction. The leukemic cells that could not be induced to differentiate lacked this capacity for desensitization, possibly due to an alteration in the uncoupling system between the receptor and adenylate cyclase. The lack of desensitization in these leukemic cells was associated with a higher sensitivity to the receptor-mediated cytotoxic effects of adrenergic hormones. It is suggested that cells, like some leukemic cells, that are unable to desensitize to adrenergic and possibly other hormones may be appropriate targets for differential destruction by hormones under conditions that do not affect normally desensitizing cells.", "contents": "Differential desensitization of functional adrenergic receptors in normal and malignant myeloid cells: relationship to receptor-mediated hormone cytotoxicity. Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells have beta(2)-adrenergic receptors, and the [(3)H]dihydroalprenolol binding was saturable, reversible, and stereospecific. The leukemic cells consisted of clones that could be induced to differentiate (MGI(+)D(+)) and clones that could not be induced to differentiate to mature macrophages and granulocytes by the protein inducer MGI. The different types of leukemic clones all had 1100-2300 receptor sites per cell, whereas normal macrophages had 7000 receptors per cell. The differentiation of MGI(+)D(+) leukemic cells was associated with an increase in receptors to a number similar to that found with normal macrophages. MGI(+)D(+) leukemic cells and normal macrophages were able to densensitize to the beta-adrenergic agonist (-)isoproterenol, shown by termination of cyclic AMP induction within 10-15 min and the lack of a second induction. The leukemic cells that could not be induced to differentiate lacked this capacity for desensitization, possibly due to an alteration in the uncoupling system between the receptor and adenylate cyclase. The lack of desensitization in these leukemic cells was associated with a higher sensitivity to the receptor-mediated cytotoxic effects of adrenergic hormones. It is suggested that cells, like some leukemic cells, that are unable to desensitize to adrenergic and possibly other hormones may be appropriate targets for differential destruction by hormones under conditions that do not affect normally desensitizing cells."}
{"id": "PMID:25441", "title": "Functional properties of beta-galactosidase from mutant strain 13 PO of Escherichia coli.", "content": "The functional properties of CZP protein, a mutant deriving from wild-type beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) by a point mutation, were investigated. A large decrease of the specificity, as evaluated by the kcat/Km ratio, was observed, principally originated by a weaker binding of the substrates. The catalytic constants, whose values are strongly affected by the presence of divalent cations, were smaller or larger for mutant enzyme than for wild-type enzyme, depending upon the experimental conditions. Analysis of the kinetic pathway indicates, with some substrates, a change in the limiting step for the mutant enzyme compared to the wild type. Because the k'3 step is rate limiting for hydrolysis of p-nitrophenyl-beta-D-galactoside by the mutant enzyme in the absence of Mg2+ and its value is relatively small, it is possible to observe a burst of p-nitrophenol during hydrolysis. This provides conclusive evidence for the occurrence of a two-step mechanism, with a sequential release of the products.", "contents": "Functional properties of beta-galactosidase from mutant strain 13 PO of Escherichia coli. The functional properties of CZP protein, a mutant deriving from wild-type beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) by a point mutation, were investigated. A large decrease of the specificity, as evaluated by the kcat/Km ratio, was observed, principally originated by a weaker binding of the substrates. The catalytic constants, whose values are strongly affected by the presence of divalent cations, were smaller or larger for mutant enzyme than for wild-type enzyme, depending upon the experimental conditions. Analysis of the kinetic pathway indicates, with some substrates, a change in the limiting step for the mutant enzyme compared to the wild type. Because the k'3 step is rate limiting for hydrolysis of p-nitrophenyl-beta-D-galactoside by the mutant enzyme in the absence of Mg2+ and its value is relatively small, it is possible to observe a burst of p-nitrophenol during hydrolysis. This provides conclusive evidence for the occurrence of a two-step mechanism, with a sequential release of the products."}
{"id": "PMID:25442", "title": "Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation.", "content": "Stereotaxic injection of kainic acid into the striatum of adult rats causes degeneration of neurons intrinsic to the striatum but spares axons of passage and of termination of extrinsic neurons. Neurochemical and histologic studies demonstrate that striatal neurons are almost insensitive to kainate at 7 days after birth and that their vulnerability increases with age; by 3 weeks after birth, striatal injection of kainate produces a lesion comparable to that of the adult. The intensity and duration of the acute behavioral response to kainate also increases with age. The maturational increase in striatal neuronal sensitivity to kainate correlates with the development of glutamatergic innervation to the striatum, as measured by [3H]glutamate uptake by synaptosomes, and with the development of a postsynaptic, high-affinity receptor site for kainate. These ontogenetic studies provide additional evidence that kainate's neurotoxicity is a receptor-mediated event related to glutamatergic innervation of vulnerable neurons.", "contents": "Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. Stereotaxic injection of kainic acid into the striatum of adult rats causes degeneration of neurons intrinsic to the striatum but spares axons of passage and of termination of extrinsic neurons. Neurochemical and histologic studies demonstrate that striatal neurons are almost insensitive to kainate at 7 days after birth and that their vulnerability increases with age; by 3 weeks after birth, striatal injection of kainate produces a lesion comparable to that of the adult. The intensity and duration of the acute behavioral response to kainate also increases with age. The maturational increase in striatal neuronal sensitivity to kainate correlates with the development of glutamatergic innervation to the striatum, as measured by [3H]glutamate uptake by synaptosomes, and with the development of a postsynaptic, high-affinity receptor site for kainate. These ontogenetic studies provide additional evidence that kainate's neurotoxicity is a receptor-mediated event related to glutamatergic innervation of vulnerable neurons."}
{"id": "PMID:25444", "title": "Evaluation of psychotropic drugs with a modified open field test.", "content": "The open field test used to study behavioral alterations induced by psychotropic drugs is based mainly in the defecation, ambulation, rearing and grooming presented by animals subjected to the test. Because of the criticisms raised against the defecation score as a measure of the central effects of drugs, in the present experiment a modification of the test is proposed for the rat. The main points that characterize the new procedure are: (1) defecation scores are not considered; (2) besides ambulation, rearing and grooming, immobility was also recorded; (3) the total time of observation was increased, and (4) the stimuli, usually presented simultaneously in the open field (light and noise), were presented separately. The results obtained suggest that it is possible to differentiate classes of psychotropic drugs, without taking the defecation and grooming scores into consideration. Besides stimulants that evoked a characteristic pattern of behavior, neuroleptics could be differentiated from anxiolytics. Similarities, according to the dose, between barbiturates and anxiolytics were detected. Under LSD a peculiar pattern of behavior characterized by a large reactivity to light was observed.", "contents": "Evaluation of psychotropic drugs with a modified open field test. The open field test used to study behavioral alterations induced by psychotropic drugs is based mainly in the defecation, ambulation, rearing and grooming presented by animals subjected to the test. Because of the criticisms raised against the defecation score as a measure of the central effects of drugs, in the present experiment a modification of the test is proposed for the rat. The main points that characterize the new procedure are: (1) defecation scores are not considered; (2) besides ambulation, rearing and grooming, immobility was also recorded; (3) the total time of observation was increased, and (4) the stimuli, usually presented simultaneously in the open field (light and noise), were presented separately. The results obtained suggest that it is possible to differentiate classes of psychotropic drugs, without taking the defecation and grooming scores into consideration. Besides stimulants that evoked a characteristic pattern of behavior, neuroleptics could be differentiated from anxiolytics. Similarities, according to the dose, between barbiturates and anxiolytics were detected. Under LSD a peculiar pattern of behavior characterized by a large reactivity to light was observed."}
{"id": "PMID:25445", "title": "Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors.", "content": "The antiparkinsonian activity of bromocriptine and of lergotrile was investigated in monkeys with surgically induced tremor and in parkinsonian patients. Both drugs effectively relieve tremor in experimental monkeys and induce less pronounced abnormal involuntary movements than L-dopa or piribedil. Both drugs were shown to be of therapeutic value in a group of patients with advanced Parkinson's disease who were no longer responsive to levodopa combined with carbidopa. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (\"on-off\" effect) were decreased, while mental changes were increased. The interactions of bromocriptine and of lergotrile with dopamine and alpha-adrenergic receptors were investigated. Both drugs have mixed agonist-antagonist activities with respect to the dopamine receptors; lergotrile has a higher affinity for the agonist site while bromocriptine has a higher affinity for the antagonist site of the receptors. Both drugs effectively displace the binding of the alpha-adrenergic antagonist WB-4101 to cerebral cortex membranes. The mechanisms underlying the antiparkinsonian efficacies of these two drugs were discussed.", "contents": "Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors. The antiparkinsonian activity of bromocriptine and of lergotrile was investigated in monkeys with surgically induced tremor and in parkinsonian patients. Both drugs effectively relieve tremor in experimental monkeys and induce less pronounced abnormal involuntary movements than L-dopa or piribedil. Both drugs were shown to be of therapeutic value in a group of patients with advanced Parkinson's disease who were no longer responsive to levodopa combined with carbidopa. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (\"on-off\" effect) were decreased, while mental changes were increased. The interactions of bromocriptine and of lergotrile with dopamine and alpha-adrenergic receptors were investigated. Both drugs have mixed agonist-antagonist activities with respect to the dopamine receptors; lergotrile has a higher affinity for the agonist site while bromocriptine has a higher affinity for the antagonist site of the receptors. Both drugs effectively displace the binding of the alpha-adrenergic antagonist WB-4101 to cerebral cortex membranes. The mechanisms underlying the antiparkinsonian efficacies of these two drugs were discussed."}
{"id": "PMID:25448", "title": "Blood pressure response to bolus administration of vasoactive drugs in the rat.", "content": "The time course of systemic blood pressure response in normotensive anaesthetized rats was studied after a bolus administration of standard doses (0.4 microgram/kg) of noradrenaline, adrenaline, isoprenaline, acetylcholine, serotonin, bradykinin, and histamine. The single stimulus of a vasoactive agent elicits a blood pressure deviation with typical phasing. The time dimension of the individual wave is less variable and less dose dependent than their amplitude. Under the given experimental conditions the blood pressure response is predominantly determined by the peripheral vasomotor reactions; the cardiac component is of minor importance. Though the overall responses to the individual drugs are quite characteristic, they seem to comprise several common components. Thus the peripheral vascular system is supposed to consist of different regulatory subsystems which take part in the systemic blood pressure control by typically timed responses. The pattern of the reaction is then given by their unequal combination and various intensity.", "contents": "Blood pressure response to bolus administration of vasoactive drugs in the rat. The time course of systemic blood pressure response in normotensive anaesthetized rats was studied after a bolus administration of standard doses (0.4 microgram/kg) of noradrenaline, adrenaline, isoprenaline, acetylcholine, serotonin, bradykinin, and histamine. The single stimulus of a vasoactive agent elicits a blood pressure deviation with typical phasing. The time dimension of the individual wave is less variable and less dose dependent than their amplitude. Under the given experimental conditions the blood pressure response is predominantly determined by the peripheral vasomotor reactions; the cardiac component is of minor importance. Though the overall responses to the individual drugs are quite characteristic, they seem to comprise several common components. Thus the peripheral vascular system is supposed to consist of different regulatory subsystems which take part in the systemic blood pressure control by typically timed responses. The pattern of the reaction is then given by their unequal combination and various intensity."}
{"id": "PMID:25449", "title": "Skin rejection in graft-versus-host disease.", "content": "Graft-versus-host disease is becoming a common clinical problem, one which can require the consultation of a plastic surgeon for restoration of skin coverage. An understanding of the immunological basis of the disease is essential to the clinical management of this condition. A case of GVHD is reported, and the principles of treatment are discussed.", "contents": "Skin rejection in graft-versus-host disease. Graft-versus-host disease is becoming a common clinical problem, one which can require the consultation of a plastic surgeon for restoration of skin coverage. An understanding of the immunological basis of the disease is essential to the clinical management of this condition. A case of GVHD is reported, and the principles of treatment are discussed."}
{"id": "PMID:25454", "title": "The effect of chronic lithium administration on dopamine metabolism in rat striatum.", "content": "Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals.", "contents": "The effect of chronic lithium administration on dopamine metabolism in rat striatum. Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals."}
{"id": "PMID:25455", "title": "Prolactin secretion during and after Noveril infusions to depressive patients.", "content": "Dibenzapine (720 mg, Noveril) was infused intravenously to 16 depressed patients during a period of 3 h. Serum prolactin levels were determined by radioimmunoassay and changes in clinical condition were evaluated according to the Hamilton Equation. The two variables were correlated to each other. In most of the patients Noveril caused a dramatic but short-lived improvement in depressive symptoms. There was much variability in the prolactin response to the drug. Serum prolactin levels showed a great elevation in 9 patients. In all patients the hormonal levels returned to their former normal levels after termination of the infusions. The treatment was then continued with Noveril per os. There was no significant correlation between serum prolactin levels and clinical condition or its change. The elevation of serum prolactin levels as a reaction to Noveril treatment may be explained by the prominent serotonergic action of Noveril. A time lag between serotonergic and dopaminergic actions of the drug when given in higher doses may be an additional explanation. Other possible hypotheses are discussed.", "contents": "Prolactin secretion during and after Noveril infusions to depressive patients. Dibenzapine (720 mg, Noveril) was infused intravenously to 16 depressed patients during a period of 3 h. Serum prolactin levels were determined by radioimmunoassay and changes in clinical condition were evaluated according to the Hamilton Equation. The two variables were correlated to each other. In most of the patients Noveril caused a dramatic but short-lived improvement in depressive symptoms. There was much variability in the prolactin response to the drug. Serum prolactin levels showed a great elevation in 9 patients. In all patients the hormonal levels returned to their former normal levels after termination of the infusions. The treatment was then continued with Noveril per os. There was no significant correlation between serum prolactin levels and clinical condition or its change. The elevation of serum prolactin levels as a reaction to Noveril treatment may be explained by the prominent serotonergic action of Noveril. A time lag between serotonergic and dopaminergic actions of the drug when given in higher doses may be an additional explanation. Other possible hypotheses are discussed."}
{"id": "PMID:25463", "title": "The degradation of a nonapeptide, sleep inducing peptide, in rat brain: comparison with enkephalin breakdown.", "content": "The degradation of delta sleep inducing peptide (DSIP) was studied and compared with that of Met-enkephalin in brain homogenates. After 7.5 minutes of incubation of 2.5% (w/v) homogenate, 30% of N-terminal tryptophan was released from DSIP, while 75% of N-terminal tyrosine was released from Metenkephalin. The optimal pH of degradation of both peptides was pH 7.35. A rapid increase of breakdown of the peptides was observed during the 10 days of postnatal growth, with breakdown expressed per unit weight of brain. Neither morphine nor deprivation of rapid eye movement (REM) sleep affected the degradation of peptides.", "contents": "The degradation of a nonapeptide, sleep inducing peptide, in rat brain: comparison with enkephalin breakdown. The degradation of delta sleep inducing peptide (DSIP) was studied and compared with that of Met-enkephalin in brain homogenates. After 7.5 minutes of incubation of 2.5% (w/v) homogenate, 30% of N-terminal tryptophan was released from DSIP, while 75% of N-terminal tyrosine was released from Metenkephalin. The optimal pH of degradation of both peptides was pH 7.35. A rapid increase of breakdown of the peptides was observed during the 10 days of postnatal growth, with breakdown expressed per unit weight of brain. Neither morphine nor deprivation of rapid eye movement (REM) sleep affected the degradation of peptides."}
{"id": "PMID:25464", "title": "In vivo and in vitro alteration of nicotine metabolism by the major metabolite of phenytoin.", "content": "The influence of hydroxyphentoin (HPPH), the major metabolite of phenytoin, on the in vitro and in vivo metabolism of nicotine was examined. In rat liver 9,000 g supernatant HPPH decreased the appearance of cotinine from nicotine by 65% while not influencing the disappearance of nicotine or the appearance of nicotine-l'-N-oxide. In vivo, HPPH inhibited both nicotine elimination and cotinine formation but did not affect nicotin-l'-N-oxide formation.", "contents": "In vivo and in vitro alteration of nicotine metabolism by the major metabolite of phenytoin. The influence of hydroxyphentoin (HPPH), the major metabolite of phenytoin, on the in vitro and in vivo metabolism of nicotine was examined. In rat liver 9,000 g supernatant HPPH decreased the appearance of cotinine from nicotine by 65% while not influencing the disappearance of nicotine or the appearance of nicotine-l'-N-oxide. In vivo, HPPH inhibited both nicotine elimination and cotinine formation but did not affect nicotin-l'-N-oxide formation."}
{"id": "PMID:25465", "title": "[The effect of mainly alpha-adrenergic drugs, indirect sympathomimetrics and dopamine on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)].", "content": "The influence of mainly alpha-adrenergic drugs (noradrenaline, adrenaline, phenylephrine), indirect sympathomimetics (ephedrine, tyramin) and dopamine on the exocrine pancreatic function of the isolated perfused organ of cats was studied. The injection of noradrenaline and adrenaline induced simultaneously a rapid depression of flow rate and an increase of perfusion pressure. Phenylephrine, indirect sympathomimetic drugs and dopamine did not change the perfusion pressure and the hydrelatic function (flow rate, secretion of chloride and total calcium). The protein and enzyme secretion was enhanced both in normal animals and cats pretreated by reserpine or 6-hydroxydopamine. The pancreatic protein secretion was inhibited by alpha-adrenolytic as well as beta-adrenolytic substances, tetracain and atropine. It is concluded, that mainly alpha-adrenergic drugs stimulate the pancreatic enzyme secretion in a cholinergic manner.", "contents": "[The effect of mainly alpha-adrenergic drugs, indirect sympathomimetrics and dopamine on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)]. The influence of mainly alpha-adrenergic drugs (noradrenaline, adrenaline, phenylephrine), indirect sympathomimetics (ephedrine, tyramin) and dopamine on the exocrine pancreatic function of the isolated perfused organ of cats was studied. The injection of noradrenaline and adrenaline induced simultaneously a rapid depression of flow rate and an increase of perfusion pressure. Phenylephrine, indirect sympathomimetic drugs and dopamine did not change the perfusion pressure and the hydrelatic function (flow rate, secretion of chloride and total calcium). The protein and enzyme secretion was enhanced both in normal animals and cats pretreated by reserpine or 6-hydroxydopamine. The pancreatic protein secretion was inhibited by alpha-adrenolytic as well as beta-adrenolytic substances, tetracain and atropine. It is concluded, that mainly alpha-adrenergic drugs stimulate the pancreatic enzyme secretion in a cholinergic manner."}
{"id": "PMID:25466", "title": "A comparison of rimiterol and salbutamol by inhalation at high and low dose in asthmatic patients.", "content": "Rimiterol hydrobromide (Pulmadil) has been shown to have a dose-related bronchodilator effect; the optimum dose by inhalation appears to lie between 200 and 1,000 microgram. When given to a group of asthmatic patients at 'recommended' and 5--10 times 'recommended' dose by aerosol, cardiovascular effects were minimal and of a magnitude similar to that of salbutamol given in the same dosages to the same patients. The very rapid bronchodilator effect of rimiterol would appear to make the drug particularly suitable for the treatment of patients with intermittent asthmatic attacks, before exercise in patients with exercise-induced asthma and for bronchodilatation before using inhaled sodium cromoglycate or corticosteroid aerosols.", "contents": "A comparison of rimiterol and salbutamol by inhalation at high and low dose in asthmatic patients. Rimiterol hydrobromide (Pulmadil) has been shown to have a dose-related bronchodilator effect; the optimum dose by inhalation appears to lie between 200 and 1,000 microgram. When given to a group of asthmatic patients at 'recommended' and 5--10 times 'recommended' dose by aerosol, cardiovascular effects were minimal and of a magnitude similar to that of salbutamol given in the same dosages to the same patients. The very rapid bronchodilator effect of rimiterol would appear to make the drug particularly suitable for the treatment of patients with intermittent asthmatic attacks, before exercise in patients with exercise-induced asthma and for bronchodilatation before using inhaled sodium cromoglycate or corticosteroid aerosols."}
{"id": "PMID:25467", "title": "A brief review of sympathomimetic bronchodilators and a description of a new selective agent, rimiterol hydrobromide.", "content": "The development of beta2-specific sympathomimetic bronchodilators (rimiterol, salbutamol, terbutaline) has made the basic treatment of asthmatic patients more safe and effective. Despite that, the asthmatics should be under careful control and all patients should be taught the correct way to use their bronchodilator aerosols. If a sympathomimetic drug has lost its effectiveness, the patient should be able to have easy contact to the treating physician or outpatient department.", "contents": "A brief review of sympathomimetic bronchodilators and a description of a new selective agent, rimiterol hydrobromide. The development of beta2-specific sympathomimetic bronchodilators (rimiterol, salbutamol, terbutaline) has made the basic treatment of asthmatic patients more safe and effective. Despite that, the asthmatics should be under careful control and all patients should be taught the correct way to use their bronchodilator aerosols. If a sympathomimetic drug has lost its effectiveness, the patient should be able to have easy contact to the treating physician or outpatient department."}
{"id": "PMID:25469", "title": "The effect of dibutyryl cyclic AMP and glucagon on the myocardial cell pH1.", "content": "DBcAMP or crystalline glucagon was utilized to elevate the intracellular cyclic AMP concentration in isolated rat hearts. Butyric acid, a metabolite of DBcAMP, was also investigated. Their effect on the intracellular pH (pHi) as determined by the distribution of [14C]DMO was investigated. Rat hearts, perfused with a recirculated modified Krebs-Henseleit solution maintained at 30 degrees C, were exposed to respiratory acidosis by bubbling the perfusate with 20% CO2. alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. Hypercapnia decreased the pHi from 7.09 to 6.82. A similar degree of hypercapnia decreased the pHi to only 6.95 in the presence of DBcAMP and to only 6.96 in the presence of glucagon. The effective buffer values (delta[HCO-3]i/deltapHi) were: control, 19; butyric acid, 16; DBcAMP, 139; glucagon, 148. These data suggest that cAMP mediates the effect of norepinephrine, which has been shown to diminish the change in pHi accompanying respiratory acidosis.", "contents": "The effect of dibutyryl cyclic AMP and glucagon on the myocardial cell pH1. DBcAMP or crystalline glucagon was utilized to elevate the intracellular cyclic AMP concentration in isolated rat hearts. Butyric acid, a metabolite of DBcAMP, was also investigated. Their effect on the intracellular pH (pHi) as determined by the distribution of [14C]DMO was investigated. Rat hearts, perfused with a recirculated modified Krebs-Henseleit solution maintained at 30 degrees C, were exposed to respiratory acidosis by bubbling the perfusate with 20% CO2. alpha- and beta-receptor antagonists were used to block the effects of endogenous catecholamines. Hypercapnia decreased the pHi from 7.09 to 6.82. A similar degree of hypercapnia decreased the pHi to only 6.95 in the presence of DBcAMP and to only 6.96 in the presence of glucagon. The effective buffer values (delta[HCO-3]i/deltapHi) were: control, 19; butyric acid, 16; DBcAMP, 139; glucagon, 148. These data suggest that cAMP mediates the effect of norepinephrine, which has been shown to diminish the change in pHi accompanying respiratory acidosis."}
{"id": "PMID:25486", "title": "Behavioral neurochemistry: neuroregulators and behavioral states.", "content": "There is compelling evidence that behavioral events after neurochemical function and that altered neurochemical function can change behavior. Such processes have been related both to neurotransmitters and to neuromodulators, together termed neuroregulators. Available research tools and theoretical constructs have begun to permit studies of certain types of behavior, primarily those related to emotional states and drives. This work is changing long-held concepts about severe mental disorders and the treatment of them.", "contents": "Behavioral neurochemistry: neuroregulators and behavioral states. There is compelling evidence that behavioral events after neurochemical function and that altered neurochemical function can change behavior. Such processes have been related both to neurotransmitters and to neuromodulators, together termed neuroregulators. Available research tools and theoretical constructs have begun to permit studies of certain types of behavior, primarily those related to emotional states and drives. This work is changing long-held concepts about severe mental disorders and the treatment of them."}
{"id": "PMID:25487", "title": "Medical treatment of mental illness.", "content": "Psychotherapeutic drugs have dramatically improved the prognosis for patients with severe mental illness. The drug treatments are not a panacea. The medications sometimes cause irreversible side effects, and they are not helpful for all patients. They allow large numbers of individuals to leave the hospital, but to return to communities that are often poorly prepared to provide continuing care. Despite their limitations, psychotherapeutic drugs relieve a great deal of human suffering. They also involve psychiatry in modern biological science. This has led to the continuing search for more effective medications based on the study of possible biochemical substrates of psychiatric disorders.", "contents": "Medical treatment of mental illness. Psychotherapeutic drugs have dramatically improved the prognosis for patients with severe mental illness. The drug treatments are not a panacea. The medications sometimes cause irreversible side effects, and they are not helpful for all patients. They allow large numbers of individuals to leave the hospital, but to return to communities that are often poorly prepared to provide continuing care. Despite their limitations, psychotherapeutic drugs relieve a great deal of human suffering. They also involve psychiatry in modern biological science. This has led to the continuing search for more effective medications based on the study of possible biochemical substrates of psychiatric disorders."}
{"id": "PMID:25488", "title": "Somatostatin--paracrine and neuromodulator peptide in gut and nervous system.", "content": "Somatostatin, a tetradecapeptide widely distributed in nervous tissue and gut, has inhibitory effects on secretion and neuromuscular activity. The actions of this peptide probably embrace three types of transmitter-receptor interaction, namely that of a neurotransmitter in the nervous system, that of a hormone in the hypophyseal portal circulation and that of a local (paracrine) effector in gut and pancreas.", "contents": "Somatostatin--paracrine and neuromodulator peptide in gut and nervous system. Somatostatin, a tetradecapeptide widely distributed in nervous tissue and gut, has inhibitory effects on secretion and neuromuscular activity. The actions of this peptide probably embrace three types of transmitter-receptor interaction, namely that of a neurotransmitter in the nervous system, that of a hormone in the hypophyseal portal circulation and that of a local (paracrine) effector in gut and pancreas."}
{"id": "PMID:25489", "title": "Comparison of cardiovascular responses and left ventricular work during exercise before and after artificial heart implantation.", "content": "Cardiovascular dynamics and left ventricular work were evaluated in 15 resting, standing, and treadmill-exercised calves before and at periodic intervals after their natural hearts (NH) were replaced with an artificial heart (AH). Standing produced increases in heart rate, cardiac output, oxygen uptake, and left ventricular work and decreases in mean aortic pressure and systemic vascular resistance in NH calves which were more marked with exercise. AH calves had higher aortic pressures, cardiac output, systemic vascular resistance, oxygen uptake, and left ventricular work during resting conditions in the first 2 postoperative weeks than did NH calves, which gradually returned to values similar to the latter by the fifth week after operation. Exercise was not tolerated early after AH implantation, but was after 5 to 6 weeks. Our results indicate that AH calves increase cardiac output with exercise by reducing systemic vascular resistance, whereas NH animals respond similarly, but also increase heart rate. The data suggest that a marked elevation in systemic vascular resistance early after AH implantation increases left ventricular work and prevents adequate rises in cardiac output to all but minor increases in metabolic requirements.", "contents": "Comparison of cardiovascular responses and left ventricular work during exercise before and after artificial heart implantation. Cardiovascular dynamics and left ventricular work were evaluated in 15 resting, standing, and treadmill-exercised calves before and at periodic intervals after their natural hearts (NH) were replaced with an artificial heart (AH). Standing produced increases in heart rate, cardiac output, oxygen uptake, and left ventricular work and decreases in mean aortic pressure and systemic vascular resistance in NH calves which were more marked with exercise. AH calves had higher aortic pressures, cardiac output, systemic vascular resistance, oxygen uptake, and left ventricular work during resting conditions in the first 2 postoperative weeks than did NH calves, which gradually returned to values similar to the latter by the fifth week after operation. Exercise was not tolerated early after AH implantation, but was after 5 to 6 weeks. Our results indicate that AH calves increase cardiac output with exercise by reducing systemic vascular resistance, whereas NH animals respond similarly, but also increase heart rate. The data suggest that a marked elevation in systemic vascular resistance early after AH implantation increases left ventricular work and prevents adequate rises in cardiac output to all but minor increases in metabolic requirements."}
{"id": "PMID:25495", "title": "Endocrine-like cells in the terminal bronchioles and saccules of human fetal lung: an ultrastructural study.", "content": "An ultrastructural study of Kulschitsky cells was made on lung tissue from five human fetuses of gestational ages between 18 and 25 weeks. The cells were found to occur with relative frequency throughout the bronchi and bronchioles, as well as in the developing saccules. This report describes in detail the cells of the terminal bronchioles and saccules, where their long cytoplasmic processes weave through the epithelium and come into contact with intercellular spaces and the lumen. The cytoplasmic organelles have an orderly arrangement comparable to secreting cells. Dense core vesicles characterise the cytoplasm but clear vesicles and some with less dense, diffuse cores are also present, and may be seen outside the plasma membrane and in the interstitial spaces. The K-cells are usually colsely associated with capillaries or smooth muscle cells across the basement membrane. In addition, the rare occurrence of a small unmyelinated nerve fibre in the vicinity of a K-cell in a terminal bronchiole raises the possibility that the cells fulfill a type of 'mini receptor' role in addition to their probable vasoactive one. Evidence is given that K-cells divide in human fetal lung.", "contents": "Endocrine-like cells in the terminal bronchioles and saccules of human fetal lung: an ultrastructural study. An ultrastructural study of Kulschitsky cells was made on lung tissue from five human fetuses of gestational ages between 18 and 25 weeks. The cells were found to occur with relative frequency throughout the bronchi and bronchioles, as well as in the developing saccules. This report describes in detail the cells of the terminal bronchioles and saccules, where their long cytoplasmic processes weave through the epithelium and come into contact with intercellular spaces and the lumen. The cytoplasmic organelles have an orderly arrangement comparable to secreting cells. Dense core vesicles characterise the cytoplasm but clear vesicles and some with less dense, diffuse cores are also present, and may be seen outside the plasma membrane and in the interstitial spaces. The K-cells are usually colsely associated with capillaries or smooth muscle cells across the basement membrane. In addition, the rare occurrence of a small unmyelinated nerve fibre in the vicinity of a K-cell in a terminal bronchiole raises the possibility that the cells fulfill a type of 'mini receptor' role in addition to their probable vasoactive one. Evidence is given that K-cells divide in human fetal lung."}
{"id": "PMID:25497", "title": "Anchoring cells (Desmocytes) in the hydrozoan polyp Cordylophora.", "content": "Desmocytes or anchoring cells are present on the upright stolons of the athecate hydroid Cordylophora caspia and function to support the soft coenosarc within the rigid tube of perisarc by linking the perisarc with the mesoglea. These cells are characterized by accumulations of 70 A filaments which aggregate into dense rods at the apical end and contact the perisarc. At the base of the desmocytes the filaments are distributed within large cytoplasmic processes which interdigitate with an extension of the mesoglea. Desmocytes in Cordylophora are temporally and spatially  formed in sequence as the upright elongates. Depending on their location and structure they can be categorized as forming, functional, or remnant desmocytes. The youngest, forming desmocytes are found in the distal end of the stolon 0.5-1.0 mm from the base of the hydranth. In this region coenosarc is just beginning to separate from the perisarc. Functional desmocytes are scattered 1-3 mm from the base of the hydranth and are associated with perpendicular extensions of the mesoglea. Remnants have lost their mesogleal connection and are located in more proximal, older regions of upright stolon. Support provided by the desmocytes to the upright stolon is limited by three factors that characterize the athecate hydroid: distribution of perisarc, pattern of growth, and extent of movement. The distal location of forming desmocytes is coincident with the hardening of new perisarc. The temporary nature of attachment sites is directly related to upright elongation. It is probable that the orientation of filaments within the cell and the mesogleal extension provide an addition feature of flexibility necessary to permit feeding, growth, and rhythmic pulsation movements characteristic of these hydroids.", "contents": "Anchoring cells (Desmocytes) in the hydrozoan polyp Cordylophora. Desmocytes or anchoring cells are present on the upright stolons of the athecate hydroid Cordylophora caspia and function to support the soft coenosarc within the rigid tube of perisarc by linking the perisarc with the mesoglea. These cells are characterized by accumulations of 70 A filaments which aggregate into dense rods at the apical end and contact the perisarc. At the base of the desmocytes the filaments are distributed within large cytoplasmic processes which interdigitate with an extension of the mesoglea. Desmocytes in Cordylophora are temporally and spatially  formed in sequence as the upright elongates. Depending on their location and structure they can be categorized as forming, functional, or remnant desmocytes. The youngest, forming desmocytes are found in the distal end of the stolon 0.5-1.0 mm from the base of the hydranth. In this region coenosarc is just beginning to separate from the perisarc. Functional desmocytes are scattered 1-3 mm from the base of the hydranth and are associated with perpendicular extensions of the mesoglea. Remnants have lost their mesogleal connection and are located in more proximal, older regions of upright stolon. Support provided by the desmocytes to the upright stolon is limited by three factors that characterize the athecate hydroid: distribution of perisarc, pattern of growth, and extent of movement. The distal location of forming desmocytes is coincident with the hardening of new perisarc. The temporary nature of attachment sites is directly related to upright elongation. It is probable that the orientation of filaments within the cell and the mesogleal extension provide an addition feature of flexibility necessary to permit feeding, growth, and rhythmic pulsation movements characteristic of these hydroids."}
{"id": "PMID:25503", "title": "Testicular descent. Normal and abnormal.", "content": "The subject of testicular descent has been reviewed. An attempt has been made to present a basic understanding of the embryology and mechanisms of this event. The abnormalities of testicular descent have also been discussed, including the pathogenesis and complications of this disorder, which is the most common developmental abnormality in childhood. The aims and results of both the hormonal and surgical treatments of cryptorchidism have been summarized. From data gleaned from the literature, a plea is made for the earlier treatment of the undescended testis in patients under five years of age.", "contents": "Testicular descent. Normal and abnormal. The subject of testicular descent has been reviewed. An attempt has been made to present a basic understanding of the embryology and mechanisms of this event. The abnormalities of testicular descent have also been discussed, including the pathogenesis and complications of this disorder, which is the most common developmental abnormality in childhood. The aims and results of both the hormonal and surgical treatments of cryptorchidism have been summarized. From data gleaned from the literature, a plea is made for the earlier treatment of the undescended testis in patients under five years of age."}
{"id": "PMID:25500", "title": "Storage of platelets prepared by discontinuous flow centrifugation.", "content": "Platelet concentrates were prepared by plateletpheresis using discontinuous flow centrifugation. Platelet units were stored in PL-146 bags of 300 ml and 2,000 ml capacity, and in vitro measures helpful in predicting platelet viability were compared. Storage in bags of 300 ml capacity led to significant fall in pH, decreased recovery from osmotic stress, and deterioration of morphology in 24 hours. Storage lesions were significantly decreased by use of 2,000 ml capacity bags.", "contents": "Storage of platelets prepared by discontinuous flow centrifugation. Platelet concentrates were prepared by plateletpheresis using discontinuous flow centrifugation. Platelet units were stored in PL-146 bags of 300 ml and 2,000 ml capacity, and in vitro measures helpful in predicting platelet viability were compared. Storage in bags of 300 ml capacity led to significant fall in pH, decreased recovery from osmotic stress, and deterioration of morphology in 24 hours. Storage lesions were significantly decreased by use of 2,000 ml capacity bags."}
{"id": "PMID:25506", "title": "The influence of pH on antimicrobial substances in canine vaginal and urethral secretions.", "content": "Trimethoprim and rosamicin (a new basic macrolide antibiotic) were administered to normal and oophorectomised female dogs by constant intravenous infusion before and after oestrogen and androgen administration. Their concentrations in plasma and in urethral and vaginal secretions were determined by bioassay and correlated with the pH values of vaginal and urethral secretions. Both compounds were concentrated in the vaginal and urethral secretions in reverse correlation with the pH of these fluids. Trimethoprim and rosamicin have antimicrobial spectra well suited for the treatment of bacterial urethritis and vaginitis and require further clinical investigation.", "contents": "The influence of pH on antimicrobial substances in canine vaginal and urethral secretions. Trimethoprim and rosamicin (a new basic macrolide antibiotic) were administered to normal and oophorectomised female dogs by constant intravenous infusion before and after oestrogen and androgen administration. Their concentrations in plasma and in urethral and vaginal secretions were determined by bioassay and correlated with the pH values of vaginal and urethral secretions. Both compounds were concentrated in the vaginal and urethral secretions in reverse correlation with the pH of these fluids. Trimethoprim and rosamicin have antimicrobial spectra well suited for the treatment of bacterial urethritis and vaginitis and require further clinical investigation."}
{"id": "PMID:25507", "title": "Milk fever prevention.", "content": "Milk fever is a disease of increasing importance. In dairy herds its incidence has doubled since 1950; today about 8 per cent of parturitions in Swedish dairy cattle are complicated by milk fever. At the same time, the clinical picture has changed and the effectiveness of calcium therapy has been markedly reduced. Thirty to 40 per cent of cows with milk fever need more than one treatment. These trends are obvious in Sweden and Norway and have been reported from many other parts of the world. However, there are also geographical and breed differences so that these figures might not be applicable under British conditions.", "contents": "Milk fever prevention. Milk fever is a disease of increasing importance. In dairy herds its incidence has doubled since 1950; today about 8 per cent of parturitions in Swedish dairy cattle are complicated by milk fever. At the same time, the clinical picture has changed and the effectiveness of calcium therapy has been markedly reduced. Thirty to 40 per cent of cows with milk fever need more than one treatment. These trends are obvious in Sweden and Norway and have been reported from many other parts of the world. However, there are also geographical and breed differences so that these figures might not be applicable under British conditions."}
{"id": "PMID:25509", "title": "Glutathione conjugation and mercapturic acid formation in the developing rat, in vivo and in vitro.", "content": "1. The levels of GSH-S-epoxidetransferase (GSH-S-transferase E, EC 2.5.1.18), gamma-glutamyl transpeptidase (EC 2.3.2.2) and S-substituted cysteine N-acetyltransferase have been measured in the liver and kidney of neonatal to adult rats. 2. GSH-S-epoxidetransferase and S-substituted cysteine N-acetyltransferase activities were less than 10% of the adult values in neonatal rats, rising gradually to reach adult values at about 40 days of age. Renal gamma-glutamyl transpeptidase activity was 27% of the adult value 2 days after birth and increased after 15 days reaching adult levels by 40 days. 3. The percentages of the doses of 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) and of 1,2-epoxybutane, administered at the same dose level to rats aged 4 days to adult, excreted as the corresponding mercapturic acids in 24 h, were not significantly different. 4. Adult and 10 day old rats doses at the same dose level with ENPP excreted N-acetyl-S-[2-hydroxy-3-(p-nitrophenoxy)propyl]-L-cysteine (ENPP-MA) at the same rate. 5. In addition to ENPP-MA, dosed rats under 13 days of age excreted the corresponding substituted cysteine. 6. The correlation between results in vitro and in vivo is discussed.", "contents": "Glutathione conjugation and mercapturic acid formation in the developing rat, in vivo and in vitro. 1. The levels of GSH-S-epoxidetransferase (GSH-S-transferase E, EC 2.5.1.18), gamma-glutamyl transpeptidase (EC 2.3.2.2) and S-substituted cysteine N-acetyltransferase have been measured in the liver and kidney of neonatal to adult rats. 2. GSH-S-epoxidetransferase and S-substituted cysteine N-acetyltransferase activities were less than 10% of the adult values in neonatal rats, rising gradually to reach adult values at about 40 days of age. Renal gamma-glutamyl transpeptidase activity was 27% of the adult value 2 days after birth and increased after 15 days reaching adult levels by 40 days. 3. The percentages of the doses of 1,2-epoxy-3-(p-nitrophenoxy)propane (ENPP) and of 1,2-epoxybutane, administered at the same dose level to rats aged 4 days to adult, excreted as the corresponding mercapturic acids in 24 h, were not significantly different. 4. Adult and 10 day old rats doses at the same dose level with ENPP excreted N-acetyl-S-[2-hydroxy-3-(p-nitrophenoxy)propyl]-L-cysteine (ENPP-MA) at the same rate. 5. In addition to ENPP-MA, dosed rats under 13 days of age excreted the corresponding substituted cysteine. 6. The correlation between results in vitro and in vivo is discussed."}
{"id": "PMID:25516", "title": "[Characteristics of pancreatic basal secretion in the dog].", "content": "A method is described for the simultaneous evaluation of the pancreatic, the biliary and the gastric secretion in long-term experiments. Under these conditions, the pancreatic basal secretion is characterized. The pancreatic basal secretion is a very variable reference value that is influenced by endogenous stimuli. The upper threshold value for the secretion rate was 2.2 ml/15 min. Under the influence of spontaneous biliary secretion, the protein concentration amounts to a characteristic value of relatively unimportant variance. If the pancreatic basal secretion is used as a reference value, the spontaneous secretions of the biliary ducts (gastrin release from the duodenum?) and of the stomach (secretin release from the duodenum) and be taken into account. A further disturbing factor interfering with both the pancreatic and the gastric basal secretion is to be neglected.", "contents": "[Characteristics of pancreatic basal secretion in the dog]. A method is described for the simultaneous evaluation of the pancreatic, the biliary and the gastric secretion in long-term experiments. Under these conditions, the pancreatic basal secretion is characterized. The pancreatic basal secretion is a very variable reference value that is influenced by endogenous stimuli. The upper threshold value for the secretion rate was 2.2 ml/15 min. Under the influence of spontaneous biliary secretion, the protein concentration amounts to a characteristic value of relatively unimportant variance. If the pancreatic basal secretion is used as a reference value, the spontaneous secretions of the biliary ducts (gastrin release from the duodenum?) and of the stomach (secretin release from the duodenum) and be taken into account. A further disturbing factor interfering with both the pancreatic and the gastric basal secretion is to be neglected."}
{"id": "PMID:25544", "title": "[Animal experiment studies on the neurohumoral control of female puberty].", "content": "To study the mode of action of oestrogen in female sexual maturation, prepubertal female rats were treated in different ways with oestradiol benzoate (OB). Using an improved implantation method, former findings on a hypophysial site of oestrogen action in the positive feedback (Hohlweg effect) were confirmed. A single s.c. injection or intrahypophysial implantation of OB at 25 or 26 days of age induced precocious vaginal opening (VO) and one ovulation, but the subsequent ovarian cycle was significantly prolonged, so that the first spontaneous ovulation occurred only at the normal time of the onset of puberty. Further studies demonstrated that the sensitivity to the ovulation-inducing effect of oestrogen increases as the rats approach the age of puberty, and that the first pubertal ovulation can be suppressed by intrahypophysial, but not by intrahypothalamic implantation of progestereone. The conclusion is drawn that the precocious induction of one ovulation via the Hohlweg effect is not tantamount to an advancement of puberty. The results furthermore suggest that the positive oestrogen feedback forms the basis for the first pubertal ovulation as it does with regard to later cyclic ovulations. True acceleration of sexual maturation was achieved by daily injections of 0,05 microgram OB/100 g b.w. from 5 days of age to VO. In contrast to findings obtained by other authors in Sprague-Dawley rats, a shortened OB treatment from 26 days of age to VO was not effective in advancing the onset of puberty unless the rats had additionally been injected with OB from 5 to 10 days of age. A final experiment demonstrated that the first ovarian cycle was not prolonged after neonatal ovariectomy and implantation of ovaries at 24, 28 or 32 days of age. Thus, maturation of the neurohormonal mechanisms that are responsible for the cyclic ovarian function continues during the prepubertal development in the absence of ovarian steroids.", "contents": "[Animal experiment studies on the neurohumoral control of female puberty]. To study the mode of action of oestrogen in female sexual maturation, prepubertal female rats were treated in different ways with oestradiol benzoate (OB). Using an improved implantation method, former findings on a hypophysial site of oestrogen action in the positive feedback (Hohlweg effect) were confirmed. A single s.c. injection or intrahypophysial implantation of OB at 25 or 26 days of age induced precocious vaginal opening (VO) and one ovulation, but the subsequent ovarian cycle was significantly prolonged, so that the first spontaneous ovulation occurred only at the normal time of the onset of puberty. Further studies demonstrated that the sensitivity to the ovulation-inducing effect of oestrogen increases as the rats approach the age of puberty, and that the first pubertal ovulation can be suppressed by intrahypophysial, but not by intrahypothalamic implantation of progestereone. The conclusion is drawn that the precocious induction of one ovulation via the Hohlweg effect is not tantamount to an advancement of puberty. The results furthermore suggest that the positive oestrogen feedback forms the basis for the first pubertal ovulation as it does with regard to later cyclic ovulations. True acceleration of sexual maturation was achieved by daily injections of 0,05 microgram OB/100 g b.w. from 5 days of age to VO. In contrast to findings obtained by other authors in Sprague-Dawley rats, a shortened OB treatment from 26 days of age to VO was not effective in advancing the onset of puberty unless the rats had additionally been injected with OB from 5 to 10 days of age. A final experiment demonstrated that the first ovarian cycle was not prolonged after neonatal ovariectomy and implantation of ovaries at 24, 28 or 32 days of age. Thus, maturation of the neurohormonal mechanisms that are responsible for the cyclic ovarian function continues during the prepubertal development in the absence of ovarian steroids."}
{"id": "PMID:25546", "title": "[Relationship between the pathogenesis of lumbosacral radiculitis and specific treatment].", "content": "On the basis of personal experience in treating 534 patients with sacro-lumbar radiculitis the authors believe it expedient to distinguish the following clinical syndromes: lumbago, radicle neuralgia, radicle neuritis, radicle neuritis with a paralysis of the foot and the caudal syndrome. In their opinion, the main pathogenetical mechanisms of the disease, which facilitates the selection of the methods of treatment should be taken into consideration. It is stressed that a differentiated clinical approach to patients with therapeutically resistent forms of sacro-lumbar radiculitis in the majority of the cases provides good results in medicational and surgical treatment.", "contents": "[Relationship between the pathogenesis of lumbosacral radiculitis and specific treatment]. On the basis of personal experience in treating 534 patients with sacro-lumbar radiculitis the authors believe it expedient to distinguish the following clinical syndromes: lumbago, radicle neuralgia, radicle neuritis, radicle neuritis with a paralysis of the foot and the caudal syndrome. In their opinion, the main pathogenetical mechanisms of the disease, which facilitates the selection of the methods of treatment should be taken into consideration. It is stressed that a differentiated clinical approach to patients with therapeutically resistent forms of sacro-lumbar radiculitis in the majority of the cases provides good results in medicational and surgical treatment."}
{"id": "PMID:25547", "title": "[Diffuse x-ray wide-angle scattering of polyglutamic acid in solution].", "content": "The diffuse wide angle x-ray scattering (WAXS) of polyglutamic acid (PGA) in solution was studied using an x-ray diffractometer with small aperture of the primary beam. The scattering  curve was recorded at an angular interval from (article: see text). The experimental scattering intensity of PGA with alpha-helical CD spectrum showed a maximum at 14.4 nm-1. Unordered PGA in solution yielded no maximum at this scattering angle. The studies have proved that the scattering theory can be applied to globular proteins in solution as well as to chain molecules in solution in this angular interval. The differences between the calculated scattering curves and the experimental curves indicate minor movements of the side chains of PGA in solutions and slight structuring of the solvent at the surface of the polypeptide chain.", "contents": "[Diffuse x-ray wide-angle scattering of polyglutamic acid in solution]. The diffuse wide angle x-ray scattering (WAXS) of polyglutamic acid (PGA) in solution was studied using an x-ray diffractometer with small aperture of the primary beam. The scattering  curve was recorded at an angular interval from (article: see text). The experimental scattering intensity of PGA with alpha-helical CD spectrum showed a maximum at 14.4 nm-1. Unordered PGA in solution yielded no maximum at this scattering angle. The studies have proved that the scattering theory can be applied to globular proteins in solution as well as to chain molecules in solution in this angular interval. The differences between the calculated scattering curves and the experimental curves indicate minor movements of the side chains of PGA in solutions and slight structuring of the solvent at the surface of the polypeptide chain."}
{"id": "PMID:25548", "title": "Substrate binding to solubilized cytochrome P-450 from rabbits at different temperatures.", "content": "The binding affinities of selected type I- and type II-substrates to partially purified cytochrome p-450 from rabbit liver microsomes were studied and found to differ from those of rats. The temperature dependence of the apparent binding constants qualitatively exhibited the same characteristics compared with that of rats. For type I-substrates endothermic and for type II-substrates exothermic reaction characteristics were observed. Taking into account the partition coefficients of the substrates so far investigated it is obvious that type I substrates with increasing hydrophobicity are bound more strongly while type II-substrates show a more complicated behvaiour. This may due to the fact that other types of binding are included besides the hydrophobic interactions.", "contents": "Substrate binding to solubilized cytochrome P-450 from rabbits at different temperatures. The binding affinities of selected type I- and type II-substrates to partially purified cytochrome p-450 from rabbit liver microsomes were studied and found to differ from those of rats. The temperature dependence of the apparent binding constants qualitatively exhibited the same characteristics compared with that of rats. For type I-substrates endothermic and for type II-substrates exothermic reaction characteristics were observed. Taking into account the partition coefficients of the substrates so far investigated it is obvious that type I substrates with increasing hydrophobicity are bound more strongly while type II-substrates show a more complicated behvaiour. This may due to the fact that other types of binding are included besides the hydrophobic interactions."}
{"id": "PMID:25549", "title": "The influence of NADH on the ethylmorphine-N-demethylation in liver microsomes from control and phenobarbital-treated rats or different ages.", "content": "The ethylmorphine-N-demethylation by liver microsomes from control and phenobarbital-treated rats of different ages was investigated by means of adding NADPH in combination  with NADH to the incubation medium. The rate of ethylmorphine-N-demethylation in the presence of NADPH without NADH is greater in adult than in young rats and greater in induced that in control rats. The higher the activity of ethylmorphine metabolism with NADPH alone the more it is abolsutely enhanced by NADH. The relative increase in ethylmorphine metabolism caused by NADH is equal in all groups of animals. It is concluded that there are no differences in the introduction of the second electron from NADH to the oxygenated cytochrome P-450 but there are differences in the concentration of cytochrome-substrate complex and, consequently, in the oxygenated cytochrome-substrate complex. The enhancing effect of NADH is higher at lower NADPH concentrations. In the presence of NADH, the NADPH concentrations necessary to obtain a msximum metabolic rate are lower than without NADH.", "contents": "The influence of NADH on the ethylmorphine-N-demethylation in liver microsomes from control and phenobarbital-treated rats or different ages. The ethylmorphine-N-demethylation by liver microsomes from control and phenobarbital-treated rats of different ages was investigated by means of adding NADPH in combination  with NADH to the incubation medium. The rate of ethylmorphine-N-demethylation in the presence of NADPH without NADH is greater in adult than in young rats and greater in induced that in control rats. The higher the activity of ethylmorphine metabolism with NADPH alone the more it is abolsutely enhanced by NADH. The relative increase in ethylmorphine metabolism caused by NADH is equal in all groups of animals. It is concluded that there are no differences in the introduction of the second electron from NADH to the oxygenated cytochrome P-450 but there are differences in the concentration of cytochrome-substrate complex and, consequently, in the oxygenated cytochrome-substrate complex. The enhancing effect of NADH is higher at lower NADPH concentrations. In the presence of NADH, the NADPH concentrations necessary to obtain a msximum metabolic rate are lower than without NADH."}
{"id": "PMID:25551", "title": "Role of neurotransmitters, prostaglandins and glucose on precursor incorporation into the RNA of thyroid slices.", "content": "The present studies were performed in order to investigate the role of neurotransmitters, prostaglandins and glucose on [3H] uridine incorporation into total RNA in beef thyroid slices. Carbamylcholine strongly stimulated RNA labelling from [3H uridine; atropine abolished this effect. NaF, at 1 and 5 mM, progressively increased this parameter while norepinephrine caused a similar effect at 10(-3) but not at 10(-6) M. Phentolamine (1 mM) blocked the stimulatory action of TSH; propranolol and atropine did not. Glucose at concentrations between 4 and 24 mM caused a progressive increase in RNA labelling from [3H] uridine. This effect was inhibited by dinitrophenol. Prostaglandins (E1, A1, F1alpha and F2alpha) assayed in concentrations between 5 and 25 microgram/ml, with or without caffeine, had no effect on RNA labelling. Moreover, neither aspirin nor indomethacin inhibited TSH stimulation. Under similar experimental conditions, PGE1 did simulate PB125I formation.", "contents": "Role of neurotransmitters, prostaglandins and glucose on precursor incorporation into the RNA of thyroid slices. The present studies were performed in order to investigate the role of neurotransmitters, prostaglandins and glucose on [3H] uridine incorporation into total RNA in beef thyroid slices. Carbamylcholine strongly stimulated RNA labelling from [3H uridine; atropine abolished this effect. NaF, at 1 and 5 mM, progressively increased this parameter while norepinephrine caused a similar effect at 10(-3) but not at 10(-6) M. Phentolamine (1 mM) blocked the stimulatory action of TSH; propranolol and atropine did not. Glucose at concentrations between 4 and 24 mM caused a progressive increase in RNA labelling from [3H] uridine. This effect was inhibited by dinitrophenol. Prostaglandins (E1, A1, F1alpha and F2alpha) assayed in concentrations between 5 and 25 microgram/ml, with or without caffeine, had no effect on RNA labelling. Moreover, neither aspirin nor indomethacin inhibited TSH stimulation. Under similar experimental conditions, PGE1 did simulate PB125I formation."}
{"id": "PMID:25552", "title": "Sympathetic amines, renin and blood pressure.", "content": "The sympathetic nervous system and the renin-angiotensin mechanism each can influence blood pressure separately but the two systems also interact functionally in various ways. There is good evidence that central catecholaminergic neurons play an essential role in the regulation of blood pressure but it may be assumed that other putative neurotransmittors such as serotonin, GABA and various peptides also participate in the central regulation of blood pressure. The secretion of renin, which catalyzes the production of angiotensin(s), is stimulated by increased sympathetic activity and circulating sympathetic amines. Dopamine seems to have an opposite effect on renin release but it is not clear whether this is due to a direct effect on the renin producing cells or an influence on sympathetic activity, centrally or peripherally.", "contents": "Sympathetic amines, renin and blood pressure. The sympathetic nervous system and the renin-angiotensin mechanism each can influence blood pressure separately but the two systems also interact functionally in various ways. There is good evidence that central catecholaminergic neurons play an essential role in the regulation of blood pressure but it may be assumed that other putative neurotransmittors such as serotonin, GABA and various peptides also participate in the central regulation of blood pressure. The secretion of renin, which catalyzes the production of angiotensin(s), is stimulated by increased sympathetic activity and circulating sympathetic amines. Dopamine seems to have an opposite effect on renin release but it is not clear whether this is due to a direct effect on the renin producing cells or an influence on sympathetic activity, centrally or peripherally."}
{"id": "PMID:25553", "title": "Cardiovascular actions of bromocriptine.", "content": "Bromocriptine lowers blood pressure in animals and in man. Results obtained in experiments performed in the dog and cat suggest three possible mechanisms of action: a) relaxation of vascular smooth muscle, principally in splanchnic and renal vessels, (b) inhibition of transmitter release from noradrenergic nerve endings, (c) central inhibition of sympathetic nerve activity. The effect of bromocriptine at each putative site of action can be explained in terms of dopamine receptor stimulation.", "contents": "Cardiovascular actions of bromocriptine. Bromocriptine lowers blood pressure in animals and in man. Results obtained in experiments performed in the dog and cat suggest three possible mechanisms of action: a) relaxation of vascular smooth muscle, principally in splanchnic and renal vessels, (b) inhibition of transmitter release from noradrenergic nerve endings, (c) central inhibition of sympathetic nerve activity. The effect of bromocriptine at each putative site of action can be explained in terms of dopamine receptor stimulation."}
{"id": "PMID:25554", "title": "Bone marrow transplantation between mixed leukocyte culture reactive siblings.", "content": "Bone marrow transplantation from an HLA identical MLC reactive sibling has been performed in a patient with acute myelogenous leukemia resistant to drug treatment. Prompt engraftment was documented; however, the patient died of septicemia 34 days after transplant. Clinical manifestation of graft vs. host reaction was mild but was moderately strong expressed at autopsy tissue samples. Recurrence of persistence of leukemia was found at the time of death.", "contents": "Bone marrow transplantation between mixed leukocyte culture reactive siblings. Bone marrow transplantation from an HLA identical MLC reactive sibling has been performed in a patient with acute myelogenous leukemia resistant to drug treatment. Prompt engraftment was documented; however, the patient died of septicemia 34 days after transplant. Clinical manifestation of graft vs. host reaction was mild but was moderately strong expressed at autopsy tissue samples. Recurrence of persistence of leukemia was found at the time of death."}
{"id": "PMID:25555", "title": "Salicylazosulphapyridine-induced Heinz body anemia.", "content": "A 58-year-old patient suffered from severe malabsorption due to agammaglobulinemia. Treated empirically with salicylazosulfapyridine 2--6 g/day, the subjective and objective features of malabsorption regressed. About a year after this treatment she developed a generalized weakness without renewal of the diarrhea; the diagnosis of Heinz body hemolytic anemia was established. In our patient, hemolysis began many months after the commencement of treatment and no deficiency of G6PD or other erythrocyte enzyme or pathological hemoglobin were found.", "contents": "Salicylazosulphapyridine-induced Heinz body anemia. A 58-year-old patient suffered from severe malabsorption due to agammaglobulinemia. Treated empirically with salicylazosulfapyridine 2--6 g/day, the subjective and objective features of malabsorption regressed. About a year after this treatment she developed a generalized weakness without renewal of the diarrhea; the diagnosis of Heinz body hemolytic anemia was established. In our patient, hemolysis began many months after the commencement of treatment and no deficiency of G6PD or other erythrocyte enzyme or pathological hemoglobin were found."}
{"id": "PMID:25556", "title": "Acid-base status during reconstructive surgery of the abdominal aorta.", "content": "Abolition of a temporary occlusion of the circulation in the legs during surgical reconstruction of the abdominal aorta generally exerts but little influence on the patient's acid-base status. The changes in acid-base status can be corrected by the patient himself. Routine administration of sodium bicarbonate or Tham is unnecessary. However, respiration, circulation and electrolyte balance should be carefully monitored to ensure that any disturbances in this respect can immediately be given adequate treatment. Determination of the acid-base status during the operation is a valuable aid in evaluation of the patient's condition and can be used as a guideline in therapy.", "contents": "Acid-base status during reconstructive surgery of the abdominal aorta. Abolition of a temporary occlusion of the circulation in the legs during surgical reconstruction of the abdominal aorta generally exerts but little influence on the patient's acid-base status. The changes in acid-base status can be corrected by the patient himself. Routine administration of sodium bicarbonate or Tham is unnecessary. However, respiration, circulation and electrolyte balance should be carefully monitored to ensure that any disturbances in this respect can immediately be given adequate treatment. Determination of the acid-base status during the operation is a valuable aid in evaluation of the patient's condition and can be used as a guideline in therapy."}
{"id": "PMID:25557", "title": "The effect of prolonged experimental hypercapnia on the brain.", "content": "Thirteen adult rabbits were exposed to a breathing air mixture containing an increasing amount of CO2 for eight weeks. When the CO2 content reached 9 Vol% the animals became apathic and lost body weight. The EEG showed a reduction of the amplitudes of 1o Hz frequences. Blood gases revealed an increase of bicarbonate but no change of pH. The blood brain barrier which was tested when the animals were killed was not disturbed. Enzyme histochemistry, light and electron microscopy revealed that moderate brain edema had occurred. From these results it is concluded that chronic hypercapnia has a hypnotic effect which in combination with chronic edema may depress vital activities considerably. However, there seem to be no irreversible morphological alterations of the brain.", "contents": "The effect of prolonged experimental hypercapnia on the brain. Thirteen adult rabbits were exposed to a breathing air mixture containing an increasing amount of CO2 for eight weeks. When the CO2 content reached 9 Vol% the animals became apathic and lost body weight. The EEG showed a reduction of the amplitudes of 1o Hz frequences. Blood gases revealed an increase of bicarbonate but no change of pH. The blood brain barrier which was tested when the animals were killed was not disturbed. Enzyme histochemistry, light and electron microscopy revealed that moderate brain edema had occurred. From these results it is concluded that chronic hypercapnia has a hypnotic effect which in combination with chronic edema may depress vital activities considerably. However, there seem to be no irreversible morphological alterations of the brain."}
{"id": "PMID:25559", "title": "Effect of lactate on FFA--release and cyclic 3', 5' AMP accumulation in fat cells at different pH.", "content": "Effect of lactate on FFA--release and cyclic 3', 5-AMP accumulation in fat cells at different pH. Acta Physiol. Pol., 1977, 28 (6): 505--510. The effect of sodium lactate on noradrenaline (NA), theophyline (Th), and dibutyryl cyclic 3', 5'AMP stimulated free fatty acid (FFA) release as well as on NA--stimulated cyclic 3', 5'AMP (cAMP) accumulation in isolated fat cells at different pH was studied. It was shown that at each of examined pH (6.8, 7.1, 7.4, 7.7) sodium lactate inhibits NA and Th-induced FFA release and NA-stimulated cAMP accumulation. It did not significantly change FFA release induced by dibutryl cyclic 3', 5'AMP. The inhibitory effect of sodium lactate both on FFA release and cAMP accumulation was markedly augmented at pH 7.1 and especially at pH 6.8 as compared to pH 7.4, while at pH 7.7 it remained essentially the same as at pH 7.4. The obtained results showed that lactate exerts its antilipolytic effect through the inhibitory action on cAMP accumulation and subsequently on the activity of the hormone-sensitive triglyceride lipase. An effect of lactate on FFA reesterification cannot be however excluded. It seems that the potentiation of the antilipolytic effect of lactate at pH below 7.4 has an important physiological significance. The mechanism protects effectively against an excessive, undesirable FFA-outflow from adipose tissue in situations in which FFA cannot be utilized.", "contents": "Effect of lactate on FFA--release and cyclic 3', 5' AMP accumulation in fat cells at different pH. Effect of lactate on FFA--release and cyclic 3', 5-AMP accumulation in fat cells at different pH. Acta Physiol. Pol., 1977, 28 (6): 505--510. The effect of sodium lactate on noradrenaline (NA), theophyline (Th), and dibutyryl cyclic 3', 5'AMP stimulated free fatty acid (FFA) release as well as on NA--stimulated cyclic 3', 5'AMP (cAMP) accumulation in isolated fat cells at different pH was studied. It was shown that at each of examined pH (6.8, 7.1, 7.4, 7.7) sodium lactate inhibits NA and Th-induced FFA release and NA-stimulated cAMP accumulation. It did not significantly change FFA release induced by dibutryl cyclic 3', 5'AMP. The inhibitory effect of sodium lactate both on FFA release and cAMP accumulation was markedly augmented at pH 7.1 and especially at pH 6.8 as compared to pH 7.4, while at pH 7.7 it remained essentially the same as at pH 7.4. The obtained results showed that lactate exerts its antilipolytic effect through the inhibitory action on cAMP accumulation and subsequently on the activity of the hormone-sensitive triglyceride lipase. An effect of lactate on FFA reesterification cannot be however excluded. It seems that the potentiation of the antilipolytic effect of lactate at pH below 7.4 has an important physiological significance. The mechanism protects effectively against an excessive, undesirable FFA-outflow from adipose tissue in situations in which FFA cannot be utilized."}
{"id": "PMID:25567", "title": "Relationship between adrenergic blocking and antihypertensive effects of beta receptor antagonists.", "content": "In hypertensive patients, whose blood pressure was decreased by racemic propranololthe dextrorotatory isomer had no antihypertensive effect. The differences in antihypertensive activity of racemic and dextrorotatory propranolol cannot be explained by different plasma levels; the data indicate that the hypotensive effect of propranolol is due to beta receptor blockade.", "contents": "Relationship between adrenergic blocking and antihypertensive effects of beta receptor antagonists. In hypertensive patients, whose blood pressure was decreased by racemic propranololthe dextrorotatory isomer had no antihypertensive effect. The differences in antihypertensive activity of racemic and dextrorotatory propranolol cannot be explained by different plasma levels; the data indicate that the hypotensive effect of propranolol is due to beta receptor blockade."}
{"id": "PMID:25568", "title": "The significance of beta1-beta2-selectivity and intrinsic sympathomimetic activity in beta-blockers, with particular reference to antihypertensive treatment.", "content": "From the findings described in the already fairly copious literature on antihypertensive therapy with beta-blockers, as well as on the basis of theoretical considerations, it may be concluded that neither cardio-selectivity nor intrinsic sympathomimetic activity is of decisive importance with regard to the blood-pressure-lowering action of these these compounds. As far as hypotensive potency alone is concerned, none of the known beta-blocking agents is fundamentally superior to the others. There are, however, considerable differences between them in respect of their safety in use, tolerability and side effects, and during long-term treatment especially these must be taken into account.", "contents": "The significance of beta1-beta2-selectivity and intrinsic sympathomimetic activity in beta-blockers, with particular reference to antihypertensive treatment. From the findings described in the already fairly copious literature on antihypertensive therapy with beta-blockers, as well as on the basis of theoretical considerations, it may be concluded that neither cardio-selectivity nor intrinsic sympathomimetic activity is of decisive importance with regard to the blood-pressure-lowering action of these these compounds. As far as hypotensive potency alone is concerned, none of the known beta-blocking agents is fundamentally superior to the others. There are, however, considerable differences between them in respect of their safety in use, tolerability and side effects, and during long-term treatment especially these must be taken into account."}
{"id": "PMID:25574", "title": "Neuropharmacology and aging.", "content": "This review has attempted to convey the idea that the current concepts of psychotropic drug actions are based largely around the monoamine transmitter systems. Several of the hypotheses which implicate abnormalities of these systems as factors involved in the aging brain are discussed. It is suggested that the current lack of specific geriatric psychotropic agents is in part a reflection of our ignorance of the neurochemical basis of the aging process.", "contents": "Neuropharmacology and aging. This review has attempted to convey the idea that the current concepts of psychotropic drug actions are based largely around the monoamine transmitter systems. Several of the hypotheses which implicate abnormalities of these systems as factors involved in the aging brain are discussed. It is suggested that the current lack of specific geriatric psychotropic agents is in part a reflection of our ignorance of the neurochemical basis of the aging process."}
{"id": "PMID:25576", "title": "Tardive dyskinesia.", "content": "The movement disorder may appear after prolonged use of antipsychotic agents. Differential diagnosis includes hereditary, infectious, toxic and drug-induced causes of extrapyramidal dysfunction. Pathophysiology appears to be related to induced changes in dopamine neuronal function and may represent irreversible extrapyramidal synaptic modification. Treatment includes removing the offending agent when possible or using the lowest effective dose if the medication cannot be totally discontinued. Indiscriminate use of antipsychotic agents in nonpsychotic patients should be avoided.", "contents": "Tardive dyskinesia. The movement disorder may appear after prolonged use of antipsychotic agents. Differential diagnosis includes hereditary, infectious, toxic and drug-induced causes of extrapyramidal dysfunction. Pathophysiology appears to be related to induced changes in dopamine neuronal function and may represent irreversible extrapyramidal synaptic modification. Treatment includes removing the offending agent when possible or using the lowest effective dose if the medication cannot be totally discontinued. Indiscriminate use of antipsychotic agents in nonpsychotic patients should be avoided."}
{"id": "PMID:25578", "title": "Persuader sex differences and peer pressure effects on attitudes toward drug abuse.", "content": "This experiment was performed to assess the effects of the experimental confederates' sex and contrived group peer pressure on the drug attitudes of male college students. Subjects were exposed to all-male or all-female groups of experimental confederates (ersuaders) who expressed either extremely pro-drug or anti-drug sentiments in a guided group discussion. A drug attitude survey encompassing four drug categories was administered immediately following the discussion. Significant differences were found between subjects in the anti-drug and pro-drug groups. The sex effect data indicated that the male subjects reported more liberal drug attitudes following exposure to female persuaders in both the anti-and pro-drug treatment conditions for the more socially acceptable drugs such as marijuana, hashish, and stimulants. Implications of these findings for possible prevention and intervention strategies and for further research are discussed.", "contents": "Persuader sex differences and peer pressure effects on attitudes toward drug abuse. This experiment was performed to assess the effects of the experimental confederates' sex and contrived group peer pressure on the drug attitudes of male college students. Subjects were exposed to all-male or all-female groups of experimental confederates (ersuaders) who expressed either extremely pro-drug or anti-drug sentiments in a guided group discussion. A drug attitude survey encompassing four drug categories was administered immediately following the discussion. Significant differences were found between subjects in the anti-drug and pro-drug groups. The sex effect data indicated that the male subjects reported more liberal drug attitudes following exposure to female persuaders in both the anti-and pro-drug treatment conditions for the more socially acceptable drugs such as marijuana, hashish, and stimulants. Implications of these findings for possible prevention and intervention strategies and for further research are discussed."}
{"id": "PMID:25579", "title": "Evaluation of some pharmaceutical aspects of intrathecal methotrexate sodium, cytarabine and hydrocortisone sodium succinate.", "content": "Methotrexate sodium, cytarabine and hydrocortisone sodium succinate were evaluated in three vehicles, Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, and Elliott's B solution, an artificial cerebrospinal fluid (CSF). Osmolarity values of all drug solutions studied were within 10% of normal human. No vehicle-related alterations in the stability of methotrexate or cytarabine were detected under simulated use conditions. However, the degradation of hydrocortisone sodium succinate was faster in Elliott's B solution than in the other vehicles. Principal differences among the vehicles involved electrolyte content, pH and buffer capacity. Elliott's B solution is similar to CSF in electrolyte composition and buffer capacity, and was the only vehicle to maintain the pH of dilute methotrexate and cytarabine solutions between 7.2 and 7.8. The significance of these in vitro data await a careful clinical study.", "contents": "Evaluation of some pharmaceutical aspects of intrathecal methotrexate sodium, cytarabine and hydrocortisone sodium succinate. Methotrexate sodium, cytarabine and hydrocortisone sodium succinate were evaluated in three vehicles, Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, and Elliott's B solution, an artificial cerebrospinal fluid (CSF). Osmolarity values of all drug solutions studied were within 10% of normal human. No vehicle-related alterations in the stability of methotrexate or cytarabine were detected under simulated use conditions. However, the degradation of hydrocortisone sodium succinate was faster in Elliott's B solution than in the other vehicles. Principal differences among the vehicles involved electrolyte content, pH and buffer capacity. Elliott's B solution is similar to CSF in electrolyte composition and buffer capacity, and was the only vehicle to maintain the pH of dilute methotrexate and cytarabine solutions between 7.2 and 7.8. The significance of these in vitro data await a careful clinical study."}
{"id": "PMID:25580", "title": "Prevalence of endocrine abnormalities in patients with the Zollinger-Ellison syndrome and in their families.", "content": "To evalute the frequency of associated and hereditary endocrinopathies in the Zollinger-Ellison syndrome, 10 patients with the syndrome were studied. In seven of them, coexisting endocrine disease was found. In six, the Zollinger-Ellison syndrome was probably a feature of multiple endocrine adenomatosis type I, whereas Cushing's syndrome in the remaining patient may have been caused by the production of an ACTH-like substance by a mixed pancreatic tumor. A total of 109 family members, including all living first degree relatives over 15 years of age, were screened for endocrine abnormalities. All six patients with evidence of multiple endocrine adenomatosis type I had relatives with endocrinopathies. In the families of the four other patients with the Zollinger-Ellison syndrome, no endocrine abnormalities were found. During this study four new cases of pituitary tumor, 17 of hyperparathyroidism, seven of the Zollinger-Ellison syndrome and one of insulinoma were detected. Although most of the disorders were asymptomatic, this clearly indicates that patients suffering from Zollinger-Ellison syndrome and also their families should undergo detailed endocrine studies.", "contents": "Prevalence of endocrine abnormalities in patients with the Zollinger-Ellison syndrome and in their families. To evalute the frequency of associated and hereditary endocrinopathies in the Zollinger-Ellison syndrome, 10 patients with the syndrome were studied. In seven of them, coexisting endocrine disease was found. In six, the Zollinger-Ellison syndrome was probably a feature of multiple endocrine adenomatosis type I, whereas Cushing's syndrome in the remaining patient may have been caused by the production of an ACTH-like substance by a mixed pancreatic tumor. A total of 109 family members, including all living first degree relatives over 15 years of age, were screened for endocrine abnormalities. All six patients with evidence of multiple endocrine adenomatosis type I had relatives with endocrinopathies. In the families of the four other patients with the Zollinger-Ellison syndrome, no endocrine abnormalities were found. During this study four new cases of pituitary tumor, 17 of hyperparathyroidism, seven of the Zollinger-Ellison syndrome and one of insulinoma were detected. Although most of the disorders were asymptomatic, this clearly indicates that patients suffering from Zollinger-Ellison syndrome and also their families should undergo detailed endocrine studies."}
{"id": "PMID:25581", "title": "Cyclophosphamide-induced remissions in advanced polyarteritis nodosa.", "content": "Two patients with far advanced polyarteritis nodosa involving multiple organ systems and with aneurysm formation demonstrable by celiac axis and renal arteriograms were treated with oral cyclophosphamide, 1 to 2 mg/kg/day, and alternate day prednisone therapy. Dramatic remissions of disease activity were achieved within weeks of initiation of therapy. Repeat angiograms obtained after one year revealed complete resolution of all aneurysms. Both patients are now receiving only cyclophosphamide and are maintained in complete remission 27 and 18 months after the start of therapy. Cyclophosphamide therapy can thus be highly effective even in far advanced polyarteritis nodosa.", "contents": "Cyclophosphamide-induced remissions in advanced polyarteritis nodosa. Two patients with far advanced polyarteritis nodosa involving multiple organ systems and with aneurysm formation demonstrable by celiac axis and renal arteriograms were treated with oral cyclophosphamide, 1 to 2 mg/kg/day, and alternate day prednisone therapy. Dramatic remissions of disease activity were achieved within weeks of initiation of therapy. Repeat angiograms obtained after one year revealed complete resolution of all aneurysms. Both patients are now receiving only cyclophosphamide and are maintained in complete remission 27 and 18 months after the start of therapy. Cyclophosphamide therapy can thus be highly effective even in far advanced polyarteritis nodosa."}
{"id": "PMID:25582", "title": "Biochemical evaluation of liver function.", "content": "Several chemistry tests for liver function are examined. Included are the transaminases, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bromsulphalein (BSP), as well as combinations of these and the ALP isoenzymes.", "contents": "Biochemical evaluation of liver function. Several chemistry tests for liver function are examined. Included are the transaminases, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bromsulphalein (BSP), as well as combinations of these and the ALP isoenzymes."}
{"id": "PMID:25583", "title": "Adoption of a manual kinetic gamma-glutamyl transferase method in the clinical laboratory.", "content": "Following our recommended protocol for establishing analytical methods in a clinical laboratory, a rapid, simplified manual kinetic method for determining Gamma-Glutamyl Transferase activity in serum was adopted to meet the needs of our laboratory. The steps taken, from the selection of the assay conditions through the introduction of the new test ot staff physicians, are described. The assay, which requires only 50 microliter of serum or plasma, uses L-gamma-glutamyl-p-nitroanilide as the substrate, and is controlled at 30C and a pH of 8.20. The reaction is monitored by the increase in absorbance at 405 nm. Up to 30 samples per hour may be analyzed using a manual spectrophotometer. The substrate is simple to prepare and is stable for one working day at room temperature and for at least one month for frozen at -20C.", "contents": "Adoption of a manual kinetic gamma-glutamyl transferase method in the clinical laboratory. Following our recommended protocol for establishing analytical methods in a clinical laboratory, a rapid, simplified manual kinetic method for determining Gamma-Glutamyl Transferase activity in serum was adopted to meet the needs of our laboratory. The steps taken, from the selection of the assay conditions through the introduction of the new test ot staff physicians, are described. The assay, which requires only 50 microliter of serum or plasma, uses L-gamma-glutamyl-p-nitroanilide as the substrate, and is controlled at 30C and a pH of 8.20. The reaction is monitored by the increase in absorbance at 405 nm. Up to 30 samples per hour may be analyzed using a manual spectrophotometer. The substrate is simple to prepare and is stable for one working day at room temperature and for at least one month for frozen at -20C."}
{"id": "PMID:25584", "title": "Immunologic aspects of malignancy.", "content": "Animal experimental studies and clinical observations closely relate the development and course of malignancy with immune function. The immune apparatus serves as a homeostatic system capable of recognizing \"sell\" from \"non-self.\" Neoplasia is characterized by new surface components against which immune reactivity may be directed. Subpopulations of lymphocytes are stimulated by such tumor antigens leading to both humoral and cellular responses. Immunodeficiency, the surveillance role of immune responses, and immune competition are intimately concerned with the eventual outcome of the malignant state. These concepts are examined as supplying the theoretical background for development of new therapeutic procedures. Immunotherapy in the future may offer the most effective means of controlling the neoplastic state.", "contents": "Immunologic aspects of malignancy. Animal experimental studies and clinical observations closely relate the development and course of malignancy with immune function. The immune apparatus serves as a homeostatic system capable of recognizing \"sell\" from \"non-self.\" Neoplasia is characterized by new surface components against which immune reactivity may be directed. Subpopulations of lymphocytes are stimulated by such tumor antigens leading to both humoral and cellular responses. Immunodeficiency, the surveillance role of immune responses, and immune competition are intimately concerned with the eventual outcome of the malignant state. These concepts are examined as supplying the theoretical background for development of new therapeutic procedures. Immunotherapy in the future may offer the most effective means of controlling the neoplastic state."}
{"id": "PMID:25585", "title": "Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade.", "content": "Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues.", "contents": "Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade. Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues."}
{"id": "PMID:25586", "title": "Renal sugar transport in the winter flounder: V. secretion of 2-deoxy-D-galactose.", "content": "Isolated renal tubules and renal clearance techniques were used to characterize the renal handling of 2-deoxy-D-galactose (2-d-Gal) by the winter flounder (Pseudopleuronectes americanus). In vitro, energy-dependent, pH-sensitive uptake of 2-d-Gal (2-100 micron) was seen at the antiluminal face of the cell. Clearance measurements showed net secretion of 2-d-Gal in vivo. The mean clearance of 2-d-Gal in 18 fish was 0.98 +/- 0.16 ml/h while the glomerular filtration rate (GFR) was only 0.37 +/- 0.10 ml/h. Secretion was associated with marked renal accumulation of both 2-d-Gal and phosphorylated derivatives (2-d-Gal-1-phosphate). Tissue-to-plasma ratios (T/P) averaged 19 for free sugar and 59 for total sugar. Both clearance ratio and T/P were reduced to approximately 1 by injection of galactose (2.5 mmol/kg) simultaneously with 2-d-Gal (25 mumol/kg). Phlorizin (2.5 mumol/kg) increased net 2-d-Gal secretion, whereas glucose (2.5 mmol/kg) produced no change in secretion. Both compounds depressed 2-d-Gal T/P. This result suggests the presence of readsorptive transport at the brush border, sensitive to glucose and phlorizin.", "contents": "Renal sugar transport in the winter flounder: V. secretion of 2-deoxy-D-galactose. Isolated renal tubules and renal clearance techniques were used to characterize the renal handling of 2-deoxy-D-galactose (2-d-Gal) by the winter flounder (Pseudopleuronectes americanus). In vitro, energy-dependent, pH-sensitive uptake of 2-d-Gal (2-100 micron) was seen at the antiluminal face of the cell. Clearance measurements showed net secretion of 2-d-Gal in vivo. The mean clearance of 2-d-Gal in 18 fish was 0.98 +/- 0.16 ml/h while the glomerular filtration rate (GFR) was only 0.37 +/- 0.10 ml/h. Secretion was associated with marked renal accumulation of both 2-d-Gal and phosphorylated derivatives (2-d-Gal-1-phosphate). Tissue-to-plasma ratios (T/P) averaged 19 for free sugar and 59 for total sugar. Both clearance ratio and T/P were reduced to approximately 1 by injection of galactose (2.5 mmol/kg) simultaneously with 2-d-Gal (25 mumol/kg). Phlorizin (2.5 mumol/kg) increased net 2-d-Gal secretion, whereas glucose (2.5 mmol/kg) produced no change in secretion. Both compounds depressed 2-d-Gal T/P. This result suggests the presence of readsorptive transport at the brush border, sensitive to glucose and phlorizin."}
{"id": "PMID:25588", "title": "Dose-related biphasic effect of prolyl-leucyl-glycinamide (MIF-I) in depression.", "content": "Five of 8 patients with unipolar or bipolar endogenous depressions taking prolyl-leucyl-glycinamide (MIF-I), 75 mg/day, showed substantial improvement within a few days of beginning treatment compared with similar improvement in only 1 of 10 receiving 750 mg/day of MIF-I and only 1 of 5 patients taking placebo. The lower dose of MIF-I was associated with significantly greater improvement than both the higher dose and placebo on all of the rating scales used. The authors suggest that an even lower dose of MIF-I, on the order of 0.1 mg/kg, may have a greater effect as an antidepressant.", "contents": "Dose-related biphasic effect of prolyl-leucyl-glycinamide (MIF-I) in depression. Five of 8 patients with unipolar or bipolar endogenous depressions taking prolyl-leucyl-glycinamide (MIF-I), 75 mg/day, showed substantial improvement within a few days of beginning treatment compared with similar improvement in only 1 of 10 receiving 750 mg/day of MIF-I and only 1 of 5 patients taking placebo. The lower dose of MIF-I was associated with significantly greater improvement than both the higher dose and placebo on all of the rating scales used. The authors suggest that an even lower dose of MIF-I, on the order of 0.1 mg/kg, may have a greater effect as an antidepressant."}
{"id": "PMID:25592", "title": "The presence of collagenolytic cathepsin in uveal lysosomes of bovine eye.", "content": "Collagenolytic cathepsin, which can liberate soluble hydroxyproline-containing products from insoluble vitreous collagen with maximum activity at pH 3.5, was biochemically studied in uveal lysosomes of bovine eye. Collagen solubilization was proportional to both enzyme concentration and incubation time. When the enzyme was heated, no reaction was observed. Collagen solubilization by uveal lysosomal extract was almost unaffected by Ca2+ ion, cysteine, beta-mercaptoethanol, and ethylenediaminetetraacetic acid, but inhibited about one-third by pepstatin. The possible role of collagenolytic cathepsin in vitreous liquefaction was considered.", "contents": "The presence of collagenolytic cathepsin in uveal lysosomes of bovine eye. Collagenolytic cathepsin, which can liberate soluble hydroxyproline-containing products from insoluble vitreous collagen with maximum activity at pH 3.5, was biochemically studied in uveal lysosomes of bovine eye. Collagen solubilization was proportional to both enzyme concentration and incubation time. When the enzyme was heated, no reaction was observed. Collagen solubilization by uveal lysosomal extract was almost unaffected by Ca2+ ion, cysteine, beta-mercaptoethanol, and ethylenediaminetetraacetic acid, but inhibited about one-third by pepstatin. The possible role of collagenolytic cathepsin in vitreous liquefaction was considered."}
{"id": "PMID:25595", "title": "[Aerobic blood sampling technique using the B 109-syringe (author's transl)].", "content": "A syringe (B 109 Radiometer) for arterial blood sampling with modified aerobic technique is described. The blood sampling and subsequent storage during 2 h in ice water induces no clinically significant changes in the pH, pCO2 and pO2 of the blood.", "contents": "[Aerobic blood sampling technique using the B 109-syringe (author's transl)]. A syringe (B 109 Radiometer) for arterial blood sampling with modified aerobic technique is described. The blood sampling and subsequent storage during 2 h in ice water induces no clinically significant changes in the pH, pCO2 and pO2 of the blood."}
{"id": "PMID:25598", "title": "Identification of phosphates on the membranes of guinea pig sperm.", "content": "Guinea pig epididymal sperm, incubated for ATPases at pH 7.0 or pH 9.0, localize reaction product on both the periacrosomal segment of the plasmalemma and the outer acrosome membrane. In other species, e.g., rabbit, Ca++-ATPase is identified with the  outer acrosome membrane. It may transport Ca++ into the acrosome for activation of enzymes released during the acrosome reaction. The neutral ATPase is demonstrable on the periacrosomal plasmalemma and possibly modifies Ca++ concentration in the fluid around the acrosome. In guinea pig sperm, Ca++-ATPase is sensitive to centrifugation or washing of sperm which indicates that the ductal fluid has unusual properties for preservation of the acrosome. Inhibition of the enzyme by these treatments suggests that conditions on the plasmalemmal surface affect the acrosome membrane. Inability to separate reaction product on the plasmalemma from that on the acrosome membrane may be due to migration of reaction product across the periacrosomal space. However, the ATPases are elicited in the guinea pig under the same conditions as in other species. The pH 9.0 enzyme requires Ca++ while the enzyme at pH 7.0 has no ion specificities. Demonstration of these enzymes indicates that mechanisms of acrosome activation, similar to those in other sperm, are relevant to the guinea pig.", "contents": "Identification of phosphates on the membranes of guinea pig sperm. Guinea pig epididymal sperm, incubated for ATPases at pH 7.0 or pH 9.0, localize reaction product on both the periacrosomal segment of the plasmalemma and the outer acrosome membrane. In other species, e.g., rabbit, Ca++-ATPase is identified with the  outer acrosome membrane. It may transport Ca++ into the acrosome for activation of enzymes released during the acrosome reaction. The neutral ATPase is demonstrable on the periacrosomal plasmalemma and possibly modifies Ca++ concentration in the fluid around the acrosome. In guinea pig sperm, Ca++-ATPase is sensitive to centrifugation or washing of sperm which indicates that the ductal fluid has unusual properties for preservation of the acrosome. Inhibition of the enzyme by these treatments suggests that conditions on the plasmalemmal surface affect the acrosome membrane. Inability to separate reaction product on the plasmalemma from that on the acrosome membrane may be due to migration of reaction product across the periacrosomal space. However, the ATPases are elicited in the guinea pig under the same conditions as in other species. The pH 9.0 enzyme requires Ca++ while the enzyme at pH 7.0 has no ion specificities. Demonstration of these enzymes indicates that mechanisms of acrosome activation, similar to those in other sperm, are relevant to the guinea pig."}
{"id": "PMID:25600", "title": "[Mosquito studies on Hiddensee].", "content": "The author reports on the biting activity of mosquitoes during the years 1957-77. His observations were made in the locality called \"Duenenheide\" on the island of Hiddensee, GDR. This \"Duenenheide\" is a heath-landscape with downs, situated near the village of Vitte. The daily rhythm of the mosquitoes is analyzed as well as the dependence on wind speed and air temperature near the ground. The results are compared with sporadic data on Stomoxys and on biting midges. The behaviour of chironomids is integrated in this comparison.", "contents": "[Mosquito studies on Hiddensee]. The author reports on the biting activity of mosquitoes during the years 1957-77. His observations were made in the locality called \"Duenenheide\" on the island of Hiddensee, GDR. This \"Duenenheide\" is a heath-landscape with downs, situated near the village of Vitte. The daily rhythm of the mosquitoes is analyzed as well as the dependence on wind speed and air temperature near the ground. The results are compared with sporadic data on Stomoxys and on biting midges. The behaviour of chironomids is integrated in this comparison."}
{"id": "PMID:25601", "title": "Histochemical identification of fiber types in canine skeletal muscle.", "content": "Proximal and distal skeletal muscles from pectoral and pelvic limbs were histochemically examined in 18 neuromuscular disease-free dogs. On the basis of the human system of classification and nomenclature and results of standard adenosine triphosphatase (ATPase) and glycine-formaldehyde preincubation procedures, the fiber types identified in immature and mature canine skeletal muscles were I, IIA, and IIC.", "contents": "Histochemical identification of fiber types in canine skeletal muscle. Proximal and distal skeletal muscles from pectoral and pelvic limbs were histochemically examined in 18 neuromuscular disease-free dogs. On the basis of the human system of classification and nomenclature and results of standard adenosine triphosphatase (ATPase) and glycine-formaldehyde preincubation procedures, the fiber types identified in immature and mature canine skeletal muscles were I, IIA, and IIC."}
{"id": "PMID:25602", "title": "Effect of liver microsome enzyme-inducing drugs on blood serum pentobarbital clearance and sleep time in sheep and rabbits.", "content": "Sheep were administered phenobarbital, diphenylhydantoin, chlorcyclizine, or phenylbutazone over 27 days. Rabbits were administered phenobarbital, diphenylhydantoin, or chlorcyclizine for 15 days. After the last treatment, pentobarbital was administered intravenously, and measurements were made of sleep time and blood serum pentobarbital concentrations over a 2-hour period. Treatment of ewes with phenobarbital or phenylbutazone increased the rate of pentobarbital clearance from the circulation and shortened sleep time; treatment with diphenylhydantoin or chlorcyclizine decreased the rates of pentobarbital clearance from blood and increased sleep time. Treatment of rabbits with phenobarbital or diphenylhydantoin accelerated pentobarbital clearance from blood and shortened sleep time; chlorcyclizine had no effect on blood pentobarbital concentrations or sleep time. The results suggest that accelerated or delayed clearance of pentobarbital from the circulation was largely responsible for shortened or prolonged sleep times. Other factors may have been involved to some extent in determining sleep time, because ewes with shortened sleep time tended to awake with lower circulating concentrations of pentobarbital than did control ewes, and those with prolonged sleep time tended to awake with higher pentobarbital values.", "contents": "Effect of liver microsome enzyme-inducing drugs on blood serum pentobarbital clearance and sleep time in sheep and rabbits. Sheep were administered phenobarbital, diphenylhydantoin, chlorcyclizine, or phenylbutazone over 27 days. Rabbits were administered phenobarbital, diphenylhydantoin, or chlorcyclizine for 15 days. After the last treatment, pentobarbital was administered intravenously, and measurements were made of sleep time and blood serum pentobarbital concentrations over a 2-hour period. Treatment of ewes with phenobarbital or phenylbutazone increased the rate of pentobarbital clearance from the circulation and shortened sleep time; treatment with diphenylhydantoin or chlorcyclizine decreased the rates of pentobarbital clearance from blood and increased sleep time. Treatment of rabbits with phenobarbital or diphenylhydantoin accelerated pentobarbital clearance from blood and shortened sleep time; chlorcyclizine had no effect on blood pentobarbital concentrations or sleep time. The results suggest that accelerated or delayed clearance of pentobarbital from the circulation was largely responsible for shortened or prolonged sleep times. Other factors may have been involved to some extent in determining sleep time, because ewes with shortened sleep time tended to awake with lower circulating concentrations of pentobarbital than did control ewes, and those with prolonged sleep time tended to awake with higher pentobarbital values."}
{"id": "PMID:25603", "title": "Cytochemical demonstration of esterases in peripheral blood leukocytes.", "content": "Cytochemical methods for alpha naphthyl acetate esterase and chloroacetate esterase have been used to identify human monocytes and granulocytes. In this study, a standard procedure for staining alpha naphthyl acetate and chloroacetate esterase activities was modified by extending the range of pH of the incubation mixture and the duration of staining and was applied to cat, dog, goat, guinea pig, hamster, human, pig, rabbit, rat, and sheep leukocytes. The results for both enzymes showed (1) incubation time and pH had discrete effects on staining and (2) species differences for in vitro conditions to demonstrate esterase activity were pronounced.", "contents": "Cytochemical demonstration of esterases in peripheral blood leukocytes. Cytochemical methods for alpha naphthyl acetate esterase and chloroacetate esterase have been used to identify human monocytes and granulocytes. In this study, a standard procedure for staining alpha naphthyl acetate and chloroacetate esterase activities was modified by extending the range of pH of the incubation mixture and the duration of staining and was applied to cat, dog, goat, guinea pig, hamster, human, pig, rabbit, rat, and sheep leukocytes. The results for both enzymes showed (1) incubation time and pH had discrete effects on staining and (2) species differences for in vitro conditions to demonstrate esterase activity were pronounced."}
{"id": "PMID:25613", "title": "[Flocculant interaction with native antibiotic solutions. The effect of flocculants on the quality indices of native solutions as dependent on a number of factors].", "content": "Flocculants had a significant effect on the characteristics of the fermentation broth filtrates of some antibiotics. They decreased the filtrate turbidity, concentration of the organic ballast, etc. The size of the floccules depended on a number of factors, including the fluocculant concentration, agitation rate, concentration of the dispersing phase in the initial filtrate. The optimal concentration of the flocculant was defined not only by the type of the antibiotic-producing organism but also by composition of the nutrient medium used for the biosynthesis. Floccculant treatment provided a significant increase in the quality of the fermentation broth filtrates with respect to the main parameters: levels of proteins, pigments, emulgation capacity.", "contents": "[Flocculant interaction with native antibiotic solutions. The effect of flocculants on the quality indices of native solutions as dependent on a number of factors]. Flocculants had a significant effect on the characteristics of the fermentation broth filtrates of some antibiotics. They decreased the filtrate turbidity, concentration of the organic ballast, etc. The size of the floccules depended on a number of factors, including the fluocculant concentration, agitation rate, concentration of the dispersing phase in the initial filtrate. The optimal concentration of the flocculant was defined not only by the type of the antibiotic-producing organism but also by composition of the nutrient medium used for the biosynthesis. Floccculant treatment provided a significant increase in the quality of the fermentation broth filtrates with respect to the main parameters: levels of proteins, pigments, emulgation capacity."}
{"id": "PMID:25614", "title": "[Rifamycin in B distribution between aqueous and organic phases].", "content": "Dependence of the coefficient of rifamycin B distribution in the system of butyl acetate-buffer solution on pH of the equilibrium acqueous phase, antibiotic concentration in the solution and temperature was studied. It was shown that the coefficient value did not depend on the antibiotic concentration within 1000-2000 gamma/ml and temperature.", "contents": "[Rifamycin in B distribution between aqueous and organic phases]. Dependence of the coefficient of rifamycin B distribution in the system of butyl acetate-buffer solution on pH of the equilibrium acqueous phase, antibiotic concentration in the solution and temperature was studied. It was shown that the coefficient value did not depend on the antibiotic concentration within 1000-2000 gamma/ml and temperature."}
{"id": "PMID:25615", "title": "Physiological conditions affecting Staphylococcus aureus susceptibility to staphylococcin 1580.", "content": "Loss of salt tolerance, irreversible loss of viability, inhibition of l-glutamic acid uptake and effects on the high energy state of the membrane were used as parameters to measure the injury induced by staphylococcin 1580, a bacteriocin of Staphylococcus epidermidis, in susceptible cells of Staphylococcus aureus Oxford 209P. A small part of a growing cell population appeared to be temporarily resistant to the bacteriocin, and the cells were arrested in this stage when suspended in buffer. The proportion of susceptible cells may rapidly shift during exponential growth, apparently concomitantly with a change in cell metabolism. Glucose- and pyruvate-grown cells were equally susceptible to salts after staphylococcin treatment. Only in pyruvate-grown cells was amino acid uptake strongly inhibited, and the membrane potential was abolished after a short lag time. Also, irreversible killing was more distinct in pyruvate-grown cells. The proton gradient across the cell membrane was only slightly disturbed in both types of cells. Specific inhibitors of the energy metabolism revealed that the high energy state of the membrane was largely supported by hydrolysis of adenosine 5'-triphosphate in glucose-grown cells, whereas the oxidative input through electron transport appeared to be relatively more important in pyruvate-grown cells. Staphylococcin 1580 affected primarily the oxidative energy metabolism, although electron transport is not inhibited. Below a distinct incubation temperature cells were completely resistant to the action of the bacteriocin. Varying the growth temperature had only a slight effect on the transition temperature, but growth in the presence of Tween 80, which greatly enhanced the proportion of unsaturated fatty acids, decreased the transition temperature.", "contents": "Physiological conditions affecting Staphylococcus aureus susceptibility to staphylococcin 1580. Loss of salt tolerance, irreversible loss of viability, inhibition of l-glutamic acid uptake and effects on the high energy state of the membrane were used as parameters to measure the injury induced by staphylococcin 1580, a bacteriocin of Staphylococcus epidermidis, in susceptible cells of Staphylococcus aureus Oxford 209P. A small part of a growing cell population appeared to be temporarily resistant to the bacteriocin, and the cells were arrested in this stage when suspended in buffer. The proportion of susceptible cells may rapidly shift during exponential growth, apparently concomitantly with a change in cell metabolism. Glucose- and pyruvate-grown cells were equally susceptible to salts after staphylococcin treatment. Only in pyruvate-grown cells was amino acid uptake strongly inhibited, and the membrane potential was abolished after a short lag time. Also, irreversible killing was more distinct in pyruvate-grown cells. The proton gradient across the cell membrane was only slightly disturbed in both types of cells. Specific inhibitors of the energy metabolism revealed that the high energy state of the membrane was largely supported by hydrolysis of adenosine 5'-triphosphate in glucose-grown cells, whereas the oxidative input through electron transport appeared to be relatively more important in pyruvate-grown cells. Staphylococcin 1580 affected primarily the oxidative energy metabolism, although electron transport is not inhibited. Below a distinct incubation temperature cells were completely resistant to the action of the bacteriocin. Varying the growth temperature had only a slight effect on the transition temperature, but growth in the presence of Tween 80, which greatly enhanced the proportion of unsaturated fatty acids, decreased the transition temperature."}
{"id": "PMID:25616", "title": "Partial characterization of a beta-lactamase from Vibrio parahaemolyticus by a new automated microiodometric technique.", "content": "A number of characteristics were determined with a new automated method for a partially purified beta-lactamase from Vibrio parahaemolyticus. The enzyme had a molecular weight of 28,000 by gel filtration, a pH optimum between 6.5 and 7.0, and a temperature optimum at 36 degrees C. With penicillin G as the substrate, the K(m) value for the beta-lactamase was 54.4 muM. The beta-lactamase was inhibited by cloxacillin but not by p-chloromercuribenzoate. The enzyme was similar but not identical to beta-lactamases from gram-negative, \"nonhalophilic\" organisms described by other workers. The microiodometric assay to measure beta-lactamase activity was automated with the use of a centrifugal analyzer that permitted 14 simultaneous determinations. Within-run precision was tested by putting the same reaction mixture in each well, and the coefficient of variation was only about 3%. Four extracts from different strains of halophilic vibrios were used to demonstrate that reaction rates were linear with enzyme concentration. The correlation coefficient of activity by the automated method with activity by the spectrophotometric method was 0.9721, demonstrating that the methods compared favorably with each other. The automated method greatly facilitated the characterization of the beta-lactamase.", "contents": "Partial characterization of a beta-lactamase from Vibrio parahaemolyticus by a new automated microiodometric technique. A number of characteristics were determined with a new automated method for a partially purified beta-lactamase from Vibrio parahaemolyticus. The enzyme had a molecular weight of 28,000 by gel filtration, a pH optimum between 6.5 and 7.0, and a temperature optimum at 36 degrees C. With penicillin G as the substrate, the K(m) value for the beta-lactamase was 54.4 muM. The beta-lactamase was inhibited by cloxacillin but not by p-chloromercuribenzoate. The enzyme was similar but not identical to beta-lactamases from gram-negative, \"nonhalophilic\" organisms described by other workers. The microiodometric assay to measure beta-lactamase activity was automated with the use of a centrifugal analyzer that permitted 14 simultaneous determinations. Within-run precision was tested by putting the same reaction mixture in each well, and the coefficient of variation was only about 3%. Four extracts from different strains of halophilic vibrios were used to demonstrate that reaction rates were linear with enzyme concentration. The correlation coefficient of activity by the automated method with activity by the spectrophotometric method was 0.9721, demonstrating that the methods compared favorably with each other. The automated method greatly facilitated the characterization of the beta-lactamase."}
{"id": "PMID:25617", "title": "Secretion of cell wall polymers into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis.", "content": "Autolysin-defective pneumococci secrete into the growth medium choline-containing macromolecules during treatment with any one of a large number of inhibitors of cell wall biosynthesis, including beta-lactams, beta-halogeno-d-alanines, cephalosporins, and d-cycloserine. Secretion is closely related to the dose response of the bacteria to the various drugs: (i) secretion can already be detected at the minimum inhibitory concentration; (ii) the rate and extent of secretion is dependent upon the drug concentration; and (iii) secretion commences within minutes after the addition of the antibiotics to the cultures. Reversal of the growth-inhibitory effect of benzylpenicillin (by penicillinase addition) is accompanied by a halt in secretion just at the time when the bacteria resume normal growth. Secretion of the choline-containing macromolecules seems to be a specific consequence of the inhibition of peptidoglycan biosynthesis, since inhibition of growth by drugs affecting protein, ribonucleic acid, or deoxyribonucleic acid synthesis does not cause secretion. The choline-containing macromolecules include both the pneumococcal lipid-containing teichoic acid (Forssman antigen) and wall teichoic acids made after the addition of antibiotics. The appearance of these macromolecules in the growth medium is not due to the hydrolytic activity of an autolysin, since penicillin-induced secretion could be demonstrated in autolysin-defective mutants, in pneumococci grown on ethanolamine-containing medium (such cells are known to have defective autolytic systems), and in wildtype pneumococci grown under conditions nonpermissive for lysis.", "contents": "Secretion of cell wall polymers into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis. Autolysin-defective pneumococci secrete into the growth medium choline-containing macromolecules during treatment with any one of a large number of inhibitors of cell wall biosynthesis, including beta-lactams, beta-halogeno-d-alanines, cephalosporins, and d-cycloserine. Secretion is closely related to the dose response of the bacteria to the various drugs: (i) secretion can already be detected at the minimum inhibitory concentration; (ii) the rate and extent of secretion is dependent upon the drug concentration; and (iii) secretion commences within minutes after the addition of the antibiotics to the cultures. Reversal of the growth-inhibitory effect of benzylpenicillin (by penicillinase addition) is accompanied by a halt in secretion just at the time when the bacteria resume normal growth. Secretion of the choline-containing macromolecules seems to be a specific consequence of the inhibition of peptidoglycan biosynthesis, since inhibition of growth by drugs affecting protein, ribonucleic acid, or deoxyribonucleic acid synthesis does not cause secretion. The choline-containing macromolecules include both the pneumococcal lipid-containing teichoic acid (Forssman antigen) and wall teichoic acids made after the addition of antibiotics. The appearance of these macromolecules in the growth medium is not due to the hydrolytic activity of an autolysin, since penicillin-induced secretion could be demonstrated in autolysin-defective mutants, in pneumococci grown on ethanolamine-containing medium (such cells are known to have defective autolytic systems), and in wildtype pneumococci grown under conditions nonpermissive for lysis."}
{"id": "PMID:25618", "title": "Characterization of cell wall polymers secreted into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis.", "content": "Autolysin-defective pneumococci secrete large quantities of choline-containing cell wall polymers into the growth medium during treatment with inhibitors of peptidoglycan synthesis. The secreted polymers were separated into three fractions by a combination of gel filtration on agarose and sodium dodecyl sulfate-gel electrophoresis. Fraction I had a high apparent molecular size and contained the Forssman antigen in complex with material exhibiting properties of cell wall teichoic acid. Choline-containing polymers of as yet uncharacterized structure were present in both fractions IIA and IIB, and fraction IIA also contained peptidoglycan components.", "contents": "Characterization of cell wall polymers secreted into the growth medium of lysis-defective pneumococci during treatment with penicillin and other inhibitors of cell wall synthesis. Autolysin-defective pneumococci secrete large quantities of choline-containing cell wall polymers into the growth medium during treatment with inhibitors of peptidoglycan synthesis. The secreted polymers were separated into three fractions by a combination of gel filtration on agarose and sodium dodecyl sulfate-gel electrophoresis. Fraction I had a high apparent molecular size and contained the Forssman antigen in complex with material exhibiting properties of cell wall teichoic acid. Choline-containing polymers of as yet uncharacterized structure were present in both fractions IIA and IIB, and fraction IIA also contained peptidoglycan components."}
{"id": "PMID:25620", "title": "Production of trypsin inhibitor by a Cephalosporium sp.", "content": "Conditions for the production of the trypsin inhibitor from Cephalosporium sp. KM 388 were investigated. Polypeptone-meat extract-glucose medium supported excellent production of the trypsin inhibitor. In this medium, polypeptone and meat extract were utilized both as carbon and nitrogen sources and as limiting substrates for the cell growth. Glucose was consumed during the stationary growth phase and prevented the disappearance of inhibitor activity. Cephalosporium sp. KM 388 grew at a rate of a first-order reaction for the cell concentrations. Trypsin inhibitor production paralleled cell growth. At 27 degrees C the maximum specific rates of growth and inhibitor production were 0.14 h-1 and 2.1 U of inhibitor/h per mg of cell, respectively. The production rate and the maximum yield of the inhibitor were increased 1.5- and 1.2-fold, respectively, when the initial pH 6.3 was maintained throughout the fermentation.", "contents": "Production of trypsin inhibitor by a Cephalosporium sp. Conditions for the production of the trypsin inhibitor from Cephalosporium sp. KM 388 were investigated. Polypeptone-meat extract-glucose medium supported excellent production of the trypsin inhibitor. In this medium, polypeptone and meat extract were utilized both as carbon and nitrogen sources and as limiting substrates for the cell growth. Glucose was consumed during the stationary growth phase and prevented the disappearance of inhibitor activity. Cephalosporium sp. KM 388 grew at a rate of a first-order reaction for the cell concentrations. Trypsin inhibitor production paralleled cell growth. At 27 degrees C the maximum specific rates of growth and inhibitor production were 0.14 h-1 and 2.1 U of inhibitor/h per mg of cell, respectively. The production rate and the maximum yield of the inhibitor were increased 1.5- and 1.2-fold, respectively, when the initial pH 6.3 was maintained throughout the fermentation."}
{"id": "PMID:25621", "title": "Role of lime treatment in the removal of bacteria, enteric viruses, and coliphages in a wastewater reclamation plant.", "content": "Lime flocculation/sedimentation in the first process unit of a 4,500-m3/day wastewater reclamation plant reduced numbers of microorganisms extensively when operated at pH 11.2. The efficiency was much less at lower pH values, and some bacteria even multiplied at pH 9.6. Data on reduction in the number of microorganisms in the lime treatment and subsequent units indicate that inactivation by hydroxide alkalinity plays an important role in the efficiency of lime treatment. Reductions in the numbers of enteric viruses were higher than those of coliphages, enterococci, and total plate and coliform bacteria, which indicate that lime treatment can be monitored by means of coliphage and conventional bacteriological tests. This paper illustrates the valuable role of high-pH lime treatment in reducing the load of pathogenic microorganisms on subsequent units, including ultimate disinfection processes, which is important in the multiple safety barrier concept of wastewater reclamation processes.", "contents": "Role of lime treatment in the removal of bacteria, enteric viruses, and coliphages in a wastewater reclamation plant. Lime flocculation/sedimentation in the first process unit of a 4,500-m3/day wastewater reclamation plant reduced numbers of microorganisms extensively when operated at pH 11.2. The efficiency was much less at lower pH values, and some bacteria even multiplied at pH 9.6. Data on reduction in the number of microorganisms in the lime treatment and subsequent units indicate that inactivation by hydroxide alkalinity plays an important role in the efficiency of lime treatment. Reductions in the numbers of enteric viruses were higher than those of coliphages, enterococci, and total plate and coliform bacteria, which indicate that lime treatment can be monitored by means of coliphage and conventional bacteriological tests. This paper illustrates the valuable role of high-pH lime treatment in reducing the load of pathogenic microorganisms on subsequent units, including ultimate disinfection processes, which is important in the multiple safety barrier concept of wastewater reclamation processes."}
{"id": "PMID:25622", "title": "Hydrogen production by Anabaena cylindrica: effects of varying ammonium and ferric ions, pH, and light.", "content": "Anabaena cylindrica sparged with argon gas produced H2 continuously for 30 days under limited light conditions (6.0 W/m2) and for 18 days under elevated light conditions (32 W/m2) in the absence of exogenous nitrogen. The efficiency of converting visible light energy (32 W/m2) into chemical energy that is trapped as H2 ranged between 0.35 and 0.85% (approximately 13 microliter of H2 per mg [drywt] per h). Ammonium additions (0.2 mM NH4+) at various times destabilized the system and eventually suppressed H2 production completely, as compared with the control. Cultures grown with 5.0 mg of Fe3+ per liter produced H2 at a rate about twice that of cultures with 0.5 mg of Fe3+ per liter. Cultures grown at pH 7.4 produced H2 at the same initial rates as cultures that were grown at pH 9.4; however, the latter cultures continued to produce H2 after CO2 deprivation.", "contents": "Hydrogen production by Anabaena cylindrica: effects of varying ammonium and ferric ions, pH, and light. Anabaena cylindrica sparged with argon gas produced H2 continuously for 30 days under limited light conditions (6.0 W/m2) and for 18 days under elevated light conditions (32 W/m2) in the absence of exogenous nitrogen. The efficiency of converting visible light energy (32 W/m2) into chemical energy that is trapped as H2 ranged between 0.35 and 0.85% (approximately 13 microliter of H2 per mg [drywt] per h). Ammonium additions (0.2 mM NH4+) at various times destabilized the system and eventually suppressed H2 production completely, as compared with the control. Cultures grown with 5.0 mg of Fe3+ per liter produced H2 at a rate about twice that of cultures with 0.5 mg of Fe3+ per liter. Cultures grown at pH 7.4 produced H2 at the same initial rates as cultures that were grown at pH 9.4; however, the latter cultures continued to produce H2 after CO2 deprivation."}
{"id": "PMID:25623", "title": "Regiospecific synthesis of isoapocodeine from 10,11-dimethoxyaporphine by using Cunninghamella elegans.", "content": "A preparative-scale regiospecific conversion of 10,11-dimethoxyaporphine to isoapocodeine was conducted with Cunninghamella elegans ATCC 9245. This biotransformation proceeded quantitatively in suspensions and was pH dependent. The influence of antioxidants on the conversion was studied. Attempts to preserve the activity of isolated C. elegans cells by a number of methods were unsuccessful.", "contents": "Regiospecific synthesis of isoapocodeine from 10,11-dimethoxyaporphine by using Cunninghamella elegans. A preparative-scale regiospecific conversion of 10,11-dimethoxyaporphine to isoapocodeine was conducted with Cunninghamella elegans ATCC 9245. This biotransformation proceeded quantitatively in suspensions and was pH dependent. The influence of antioxidants on the conversion was studied. Attempts to preserve the activity of isolated C. elegans cells by a number of methods were unsuccessful."}
{"id": "PMID:25624", "title": "Immobilization of Aspergillus beta-glucosidase on chitosan.", "content": "beta-Glucosidase of Aspergillus phoenicis QM 329 was immobilized on chitosan, using the bifunctional agent glutaraldehyde. The most active preparation based on the amount of support contained a 1:2.5 enzyme-to-chitosan ratio (wt/wt). However, the specific activity of the bound enzyme decreased from 10 to 1% with increasing enzyme-to-chitosan ratio. Compared with free beta-glucosidase, the immobilized enzyme exhibited: (i) a similar pH optimum but more activity at lower pH values; (ii) improved thermal stability; (iii) a similar response to inhibition by glucose; and (iv) mass transfer limitations as reflected by higher apparent Km and lower energy of activation.", "contents": "Immobilization of Aspergillus beta-glucosidase on chitosan. beta-Glucosidase of Aspergillus phoenicis QM 329 was immobilized on chitosan, using the bifunctional agent glutaraldehyde. The most active preparation based on the amount of support contained a 1:2.5 enzyme-to-chitosan ratio (wt/wt). However, the specific activity of the bound enzyme decreased from 10 to 1% with increasing enzyme-to-chitosan ratio. Compared with free beta-glucosidase, the immobilized enzyme exhibited: (i) a similar pH optimum but more activity at lower pH values; (ii) improved thermal stability; (iii) a similar response to inhibition by glucose; and (iv) mass transfer limitations as reflected by higher apparent Km and lower energy of activation."}
{"id": "PMID:25625", "title": "Physiology of L-asparaginase synthesis in recombinants of Escherichia coli A-1.", "content": "A mating between Escherichia coli 4318 (thi leu Las- Hfr) and E. coli A-1 (Met- Las+ F-) resulted in the formation of prototrophic recombinants having L-asparaginase activities at three distinct levels. The physiology of L-asparaginase synthesis in these recombinants is decribed. One class of recombinants produced significantly more L-asparaginase than E. coli A-1. L-Asparaginase synthesis in the recombinants was inhibited by the presence of dissolved oxygen in the medium and was transiently repressed by the presence of glucose in the same manner as that observed in the parental strains. L-Asparaginase activity was increased by the addition of oxalacetate as well as other members of the tricarboxylic acid cycle.", "contents": "Physiology of L-asparaginase synthesis in recombinants of Escherichia coli A-1. A mating between Escherichia coli 4318 (thi leu Las- Hfr) and E. coli A-1 (Met- Las+ F-) resulted in the formation of prototrophic recombinants having L-asparaginase activities at three distinct levels. The physiology of L-asparaginase synthesis in these recombinants is decribed. One class of recombinants produced significantly more L-asparaginase than E. coli A-1. L-Asparaginase synthesis in the recombinants was inhibited by the presence of dissolved oxygen in the medium and was transiently repressed by the presence of glucose in the same manner as that observed in the parental strains. L-Asparaginase activity was increased by the addition of oxalacetate as well as other members of the tricarboxylic acid cycle."}
{"id": "PMID:25626", "title": "PR toxin production in different Penicillium roqueforti strains.", "content": "Different Penicillium roqueforti strains from the American Type Culture Collection were tested for the production of PR toxin. All four strains were able to produce the toxin on semisynthetic medium at 24 degrees C after certain periods of incubation. The yields were correlated with the pH of the medium. Timing of the harvest influenced both the yield and purification of the toxin.", "contents": "PR toxin production in different Penicillium roqueforti strains. Different Penicillium roqueforti strains from the American Type Culture Collection were tested for the production of PR toxin. All four strains were able to produce the toxin on semisynthetic medium at 24 degrees C after certain periods of incubation. The yields were correlated with the pH of the medium. Timing of the harvest influenced both the yield and purification of the toxin."}
{"id": "PMID:25628", "title": "Endocrine studies in Fanconi's anaemia. Report of 4 cases.", "content": "Four boys with Fanconi's anaemia and growth hormone (GH) deficiency are reported. Case 1 had isolated GH deficiency and responded to HGH and to oxandrolone treatment. Case 2, his brother, had milder haematological and dysmorphic manifestations and maintained a low-normal growth rate without treatment in spite of laboratory evidence of GH deficiency. Case 3 had multiple hypothalamopituitary defects, including deficiencies of GH, ACTH, and gonadotrophins. Case 4 had isolated GH deficiency and responded moderately well to HGH treatment. 3 of the 4 patients had bilateral cryptorchidism, 2 with increased plasma gonadotrophins, indicating primary testicular failure. We conclude that GH deficiency, isolated or combined with other hypothalamopituitary defects, and primary testicular failure with cryptorchidism are frequent but not constant features of Fanconi's anaemia.", "contents": "Endocrine studies in Fanconi's anaemia. Report of 4 cases. Four boys with Fanconi's anaemia and growth hormone (GH) deficiency are reported. Case 1 had isolated GH deficiency and responded to HGH and to oxandrolone treatment. Case 2, his brother, had milder haematological and dysmorphic manifestations and maintained a low-normal growth rate without treatment in spite of laboratory evidence of GH deficiency. Case 3 had multiple hypothalamopituitary defects, including deficiencies of GH, ACTH, and gonadotrophins. Case 4 had isolated GH deficiency and responded moderately well to HGH treatment. 3 of the 4 patients had bilateral cryptorchidism, 2 with increased plasma gonadotrophins, indicating primary testicular failure. We conclude that GH deficiency, isolated or combined with other hypothalamopituitary defects, and primary testicular failure with cryptorchidism are frequent but not constant features of Fanconi's anaemia."}
{"id": "PMID:25629", "title": "Luteinising hormone-releasing hormone nasal spray as therapy for undescended testicle.", "content": "Twenty-two prepubertal children with unilateral cryptorchidism were treated. None had undergone previous medical or surgical to modify the abnormal position of the testes, all of which were located inthe inguinal canal. Treatment was with luteinising hormone-releasing hormone (LH-RH) nasal spray given for 7 days. 9 boys insufflated 100 microgram LH-RH in each nostril  6 times per 24 hours (1200 microgram/24 h); the remaining 13 boys insufflated 500 microgram 12-hourly (1000 microgram/24 h). An LH-RH test (500 microgram IV) was carried out before and after therapy. Full descent of the testis into the scrotum was obtained in 7 out of the 22 cases; in a further 6 cases the testis moved down the inguinal canal. Basal values of luteinising hormone and follicle-stimulating hormone and those for pituitary reserve remained unchanged before and after therapy, and were similar to the values of a control group. No correlation was found between response to therapy and bone age, testosterone level in serum, basal values or pituitary reserve of luteinising hormone or follicle-stimulating hormone.", "contents": "Luteinising hormone-releasing hormone nasal spray as therapy for undescended testicle. Twenty-two prepubertal children with unilateral cryptorchidism were treated. None had undergone previous medical or surgical to modify the abnormal position of the testes, all of which were located inthe inguinal canal. Treatment was with luteinising hormone-releasing hormone (LH-RH) nasal spray given for 7 days. 9 boys insufflated 100 microgram LH-RH in each nostril  6 times per 24 hours (1200 microgram/24 h); the remaining 13 boys insufflated 500 microgram 12-hourly (1000 microgram/24 h). An LH-RH test (500 microgram IV) was carried out before and after therapy. Full descent of the testis into the scrotum was obtained in 7 out of the 22 cases; in a further 6 cases the testis moved down the inguinal canal. Basal values of luteinising hormone and follicle-stimulating hormone and those for pituitary reserve remained unchanged before and after therapy, and were similar to the values of a control group. No correlation was found between response to therapy and bone age, testosterone level in serum, basal values or pituitary reserve of luteinising hormone or follicle-stimulating hormone."}
{"id": "PMID:25631", "title": "Acute response to acid-base stress.", "content": "A method previously established in the experimental animal for predicting the acute response to either metabolic stress (bicarbonate administration) or respiratory stress(manipulation of oxygenator gas during cardiopulmonary bypass) has been extended to man. The method is based on a single nomogram. The accuracy of the nomogram is demonstrated using data from 13 patients on cardiopulmonary bypass. Similar agreement obtains between the nomogram and data reported by others. The nomogram can be used to estimate the therapeutically required dose of bicarbonate.", "contents": "Acute response to acid-base stress. A method previously established in the experimental animal for predicting the acute response to either metabolic stress (bicarbonate administration) or respiratory stress(manipulation of oxygenator gas during cardiopulmonary bypass) has been extended to man. The method is based on a single nomogram. The accuracy of the nomogram is demonstrated using data from 13 patients on cardiopulmonary bypass. Similar agreement obtains between the nomogram and data reported by others. The nomogram can be used to estimate the therapeutically required dose of bicarbonate."}
{"id": "PMID:25632", "title": "Renal concentration gradients of salicylic acid and its metabolic congeners in the dog.", "content": "Salicylic acid and its principal metabolic product, salicyluric acid, are ultrafiltered at the glomeruli, secreted by the proximal segment and undergo back diffusion; the net effect being an accumulation of salicylates in the cortex. The back diffusion of salicylate is pH-sensitive (salicylurate is not) and its secretion is less sensitive than that of salicylurate to depression by probenecid. There was an increasing concentration gradient of these salicylates from outer cortex to innermost medulla. The clearance of salicyluric acid exceeded glomerular filtration rate even at very low urine flow and was not pH-dependent, so that total salicylate accumulation in the medulla was less affected by adjustment of urinary pH. Increasing perfusion of the nephron markedly reduced the inner medulla/cortical concentration ratios and segmental concentrations of salt and urea and reduced the cortical concentrations of salicylates. Diuresis may decrease the medullary concentration of salicylates, depending on the rate and duration of increased urine flow.", "contents": "Renal concentration gradients of salicylic acid and its metabolic congeners in the dog. Salicylic acid and its principal metabolic product, salicyluric acid, are ultrafiltered at the glomeruli, secreted by the proximal segment and undergo back diffusion; the net effect being an accumulation of salicylates in the cortex. The back diffusion of salicylate is pH-sensitive (salicylurate is not) and its secretion is less sensitive than that of salicylurate to depression by probenecid. There was an increasing concentration gradient of these salicylates from outer cortex to innermost medulla. The clearance of salicyluric acid exceeded glomerular filtration rate even at very low urine flow and was not pH-dependent, so that total salicylate accumulation in the medulla was less affected by adjustment of urinary pH. Increasing perfusion of the nephron markedly reduced the inner medulla/cortical concentration ratios and segmental concentrations of salt and urea and reduced the cortical concentrations of salicylates. Diuresis may decrease the medullary concentration of salicylates, depending on the rate and duration of increased urine flow."}
{"id": "PMID:25633", "title": "Effects of l-penbutolol (Hoe 893d) on the transmembrane potentials of canine purkinje fibers and ventricular muscle fibers.", "content": "Intrinsic membrane effects (non-specific effects) and beta-adrenergic blocking action (specific effects) of l-penbutolol were studied using intracellular microelectrode techniques. l-Penbutolol in concentrations above 0.1 mg/L reduced the maximum rate of depolarization at phase O of both Purkinje fibers and ventricular muscle fibers without affecting their maximum diastolic potential. The action potential duration of Purkinje fibers were also shortened. The shortening of action potential duration and enhancement of automaticity in Purkinje fibers, normally induced by isoproterenol (0.2 mg/L), were antagonized by l-penbutolol in much lower concentraions (0.1--1.0 microgram/L) than those at which nonspecific effects are observed. The difference between these two concentration ranges is sufficient to suggest that l-penbutolol might be a highly specific beta-adrenergic blocking agent.", "contents": "Effects of l-penbutolol (Hoe 893d) on the transmembrane potentials of canine purkinje fibers and ventricular muscle fibers. Intrinsic membrane effects (non-specific effects) and beta-adrenergic blocking action (specific effects) of l-penbutolol were studied using intracellular microelectrode techniques. l-Penbutolol in concentrations above 0.1 mg/L reduced the maximum rate of depolarization at phase O of both Purkinje fibers and ventricular muscle fibers without affecting their maximum diastolic potential. The action potential duration of Purkinje fibers were also shortened. The shortening of action potential duration and enhancement of automaticity in Purkinje fibers, normally induced by isoproterenol (0.2 mg/L), were antagonized by l-penbutolol in much lower concentraions (0.1--1.0 microgram/L) than those at which nonspecific effects are observed. The difference between these two concentration ranges is sufficient to suggest that l-penbutolol might be a highly specific beta-adrenergic blocking agent."}
{"id": "PMID:25634", "title": "Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156.", "content": "RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action.", "contents": "Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156. RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action."}
{"id": "PMID:25635", "title": "Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia.", "content": "Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis.", "contents": "Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia. Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis."}
{"id": "PMID:25636", "title": "Effects of host aging, ions, and pH on the adsorption of the cyanovirus N-1 to Nostoc muscorum.", "content": "The adsorption rate of the cyanovirus N-1 infecting the nitrogen-fixing blue-green alga Nostocmuscorum decreased with aging of algal cultures and the virus failed to adsorb to the dead host cells. The adsorption rate declined in saline magnesium chloride solution compared to that in algal growth medium. The addition of amino acids like L-tryptophan and L-phenylalanine failed to enhance the adsorption rate of the virus. Optimal pH of adsorption was 7.6 to 8;1.", "contents": "Effects of host aging, ions, and pH on the adsorption of the cyanovirus N-1 to Nostoc muscorum. The adsorption rate of the cyanovirus N-1 infecting the nitrogen-fixing blue-green alga Nostocmuscorum decreased with aging of algal cultures and the virus failed to adsorb to the dead host cells. The adsorption rate declined in saline magnesium chloride solution compared to that in algal growth medium. The addition of amino acids like L-tryptophan and L-phenylalanine failed to enhance the adsorption rate of the virus. Optimal pH of adsorption was 7.6 to 8;1."}
{"id": "PMID:25639", "title": "A comparative study of five commercial reagents for the Coulter Model S: a proposed method for reagent evaluation.", "content": "A comparative study of five competitive commercial reagents for the Coulter Model S was performed jointly by two large, busy hospital laboratories with active quality control programs. Both laboratories, independently using the same reagent systems, studied 20 consecutive blood samples from patients from their own respective hospital for 20 days. Data from both laboratories were analyzed by standard and nonstandard statistical methods, and the results from both laboratories were compared. Although all reagent systems performed reasonably well in a clinical setting, highly significant statistical differences in their precisions were demonstrated by using univariate and multivariate techniques. The statistical method developed in this study can be applied to other systematic investigations that compare reagent systems.", "contents": "A comparative study of five commercial reagents for the Coulter Model S: a proposed method for reagent evaluation. A comparative study of five competitive commercial reagents for the Coulter Model S was performed jointly by two large, busy hospital laboratories with active quality control programs. Both laboratories, independently using the same reagent systems, studied 20 consecutive blood samples from patients from their own respective hospital for 20 days. Data from both laboratories were analyzed by standard and nonstandard statistical methods, and the results from both laboratories were compared. Although all reagent systems performed reasonably well in a clinical setting, highly significant statistical differences in their precisions were demonstrated by using univariate and multivariate techniques. The statistical method developed in this study can be applied to other systematic investigations that compare reagent systems."}
{"id": "PMID:25642", "title": "Acidification of rat colon with lactulose. Its effects on the healing of colonic anastomoses.", "content": "Preoperative preparation of rats with lactulose, 2.5 ml/kg of a 52.5% w/w solution, for two days resulted in increased bursting pressure and bursting wall tension of low colonic anastomoses three days postoperatively when compared with unprepared controls (85.8, viz, 36.1 mm Hg and 0.55, viz, 0.19 dynes/cm X 10(-5). After seven days, there was no appreciable difference in the rats with colonic acidification and in the controls.", "contents": "Acidification of rat colon with lactulose. Its effects on the healing of colonic anastomoses. Preoperative preparation of rats with lactulose, 2.5 ml/kg of a 52.5% w/w solution, for two days resulted in increased bursting pressure and bursting wall tension of low colonic anastomoses three days postoperatively when compared with unprepared controls (85.8, viz, 36.1 mm Hg and 0.55, viz, 0.19 dynes/cm X 10(-5). After seven days, there was no appreciable difference in the rats with colonic acidification and in the controls."}
{"id": "PMID:25644", "title": "Instability of the bovine MOR-2AB (mitochondrial malate: NAD oxidoreductase) heterodimeric molecule of heterozygous subjects after isoelectric focusing.", "content": "The heterodimeric molecule which is characteristic of animals heterozygous for the MOR-2 polymorphism and which is readily seen on enzymograms after electrophoresis is reported to be absent from zymograms performed after isoelectric focusing. A possible explanation is presented based on monomer--dimer equilibrium at pH 8.0--8.5.", "contents": "Instability of the bovine MOR-2AB (mitochondrial malate: NAD oxidoreductase) heterodimeric molecule of heterozygous subjects after isoelectric focusing. The heterodimeric molecule which is characteristic of animals heterozygous for the MOR-2 polymorphism and which is readily seen on enzymograms after electrophoresis is reported to be absent from zymograms performed after isoelectric focusing. A possible explanation is presented based on monomer--dimer equilibrium at pH 8.0--8.5."}
{"id": "PMID:25645", "title": "Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1c) from wild mice.", "content": "We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1c) in a population of wild mice. The Gpi-1c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1a or Gpi-1b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal Km's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1c show only mild hematological symptoms. The frequency of Gpi-1c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1d is reported.", "contents": "Biochemical genetics of a new glucosephosphate isomerase allele (Gpi-1c) from wild mice. We have found a new allele at the structural locus for glucosephosphate isomerase (called Gpi-1c) in a population of wild mice. The Gpi-1c allele codes for an enzyme of greater cathodal electrophoretic mobility than either the Gpi-1a or Gpi-1b alleles found in the wild and in the SM/J and C57BL/6J inbred strains. Mice homozygous for Gpi-1c have erythrocyte enzyme activity reduced to 33% of normal levels, altered pH profile, lowered heat stability, and normal Km's when compared with SM/J and C57BL/6J mice. The activity of the enzyme in brain, liver, and kidney is not so markedly lowered, although the electrophoretic mobility, pH profile, and heat stability are altered in these tissues. Deficiencies of erythrocyte glucosephosphate isomerase in man, to this level, can cause severe hemolytic anemia. Homozygotes for Gpi-1c show only mild hematological symptoms. The frequency of Gpi-1c in wild populations of mice is discussed and the occurrence of a further rare allele Gpi-1d is reported."}
{"id": "PMID:25646", "title": "Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives.", "content": "By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.", "contents": "Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives. By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made."}
{"id": "PMID:25647", "title": "Magnetic coupling of the molybdenum and iron-sulphur centres in xanthine oxidase and xanthine dehydrogenases.", "content": "Magnetic interaction between molybdenum and one of the iron-sulphur centres in milk xanthine oxidase [Lowe, Lynden-Bell & Bray (1972) Biochem. J. 130, 239-249] was studied further, with particular reference to the newly discovered Mo(V) e.p.r.(electron-paramagnetic-resonance) signal, Resting II [Lowe, Barber, Pawlik & Bray (1976) Biochem. J. 155, 81-85]. E.p.r. measurements at 35GHz near to 4.2K showed that the interaction has the same sign at all molybdenum orientations and is ferromagnetic. The predicted splitting of the e.p.r. signal from the reduced iron-sulphur centre, Fe/S I, was observed, Providing positive identification of this as the other interacting species. Chemical modification of the molybdenum environment in xanthine oxidase can change the size of the interaction severalfold, but interaction always remains approximately isotropic. The interaction in turkey liver xanthine dehydrogenase is indistinguishable from that in the oxidase. However, a bacterial xanthine dehydrogenase with different iron-sulphur centres shows rather larger interaction. Guanidinium chloride disturbs the iron-sulphur centres of the oxidase, and when this occurs there is a parallel and relatively small change in the interaction. Removal of flavin from the molecule, or raising the pH to 12.0, changes the interaction slightly without affecting the chromophores themselves. It is concluded that the Fe/S I centre and the Mo are at least 1.0nm and probably nearer 2.5nm apart, and that the conformation of the protein between them is relatively stable up to pH 12.", "contents": "Magnetic coupling of the molybdenum and iron-sulphur centres in xanthine oxidase and xanthine dehydrogenases. Magnetic interaction between molybdenum and one of the iron-sulphur centres in milk xanthine oxidase [Lowe, Lynden-Bell & Bray (1972) Biochem. J. 130, 239-249] was studied further, with particular reference to the newly discovered Mo(V) e.p.r.(electron-paramagnetic-resonance) signal, Resting II [Lowe, Barber, Pawlik & Bray (1976) Biochem. J. 155, 81-85]. E.p.r. measurements at 35GHz near to 4.2K showed that the interaction has the same sign at all molybdenum orientations and is ferromagnetic. The predicted splitting of the e.p.r. signal from the reduced iron-sulphur centre, Fe/S I, was observed, Providing positive identification of this as the other interacting species. Chemical modification of the molybdenum environment in xanthine oxidase can change the size of the interaction severalfold, but interaction always remains approximately isotropic. The interaction in turkey liver xanthine dehydrogenase is indistinguishable from that in the oxidase. However, a bacterial xanthine dehydrogenase with different iron-sulphur centres shows rather larger interaction. Guanidinium chloride disturbs the iron-sulphur centres of the oxidase, and when this occurs there is a parallel and relatively small change in the interaction. Removal of flavin from the molecule, or raising the pH to 12.0, changes the interaction slightly without affecting the chromophores themselves. It is concluded that the Fe/S I centre and the Mo are at least 1.0nm and probably nearer 2.5nm apart, and that the conformation of the protein between them is relatively stable up to pH 12."}
{"id": "PMID:25648", "title": "Pyruvate carboxylase from a thermophilic Bacillus. Studies on the specificity of activation by acyl derivatives of coenzyme A and on the properties of catalysis in the absence of activator.", "content": "1. Oxaloacetate synthesis catalysed by pyruvate carboxylase from a thermophilic Bacillus in the absence of acetyl-CoA required addition of high concentrations of pyruvate, MgATP(2-) and HCO(3) (-), and at 45 degrees C occurred at a maximum rate approx. 20% of that in the presence of a saturating concentration of acetyl-CoA. The apparent K(m) for HCO(3) (-) at pH7.8 was 400mm without acetyl-CoA, and 16mm with a saturating activator concentration. The relationship between reciprocal initial rate and reciprocal MgATP(2-) concentration was non-linear (convex-down) in the absence of acetyl-CoA, but the extent of deviation decreased as the activator concentration was increased. The relationship between reciprocal initial rate and reciprocal pyruvate concentration was non-linear (convex-down) in the presence or absence of acetyl-CoA. 2. The optimum pH for catalysis of oxaloacetate synthesis was similar in the presence or absence of acetyl-CoA. The variation with pH of apparent K(m) for HCO(3) (-) implicated residue(s) with pK(a) 8.6 in catalysis of the activator-independent oxaloacetate synthesis. 3. Linear Arrhenius and van't Hoff plots were observed for the temperature-dependence of oxaloacetate synthesis in the absence of acetyl-CoA over the range 25-55 degrees C. E(a) (activation energy) was 56.3kJ/mol and DeltaH(double dagger) (HCO(3) (-)) (enthalpy of activation) was -38.6kJ/mol. In the presence of acetyl-CoA, biphasic Arrhenius and van't Hoff plots are observed with a change of slope at 30 degrees C in each case. E(a) was 43.7 and 106.3kJ/mol above and below 30 degrees C respectively. 4. Incubation of Bacillus pyruvate carboxylase with trinitrobenzenesulphonate caused specific inactivation of acetyl-CoA-dependent catalytic activity associated with the incorporation of 1.3+/-0.2 trinitrophenyl residues per subunit. Activator-independent catalysis and regulatory inhibition by l-aspartate were unaffected. The rate of inactivation of acetyl-CoA-dependent catalysis by trinitrobenzenesulphonate was specifically decreased by addition of acetyl-CoA and other acetyl-CoA and other acyl-CoA species, but complete protection was not obtained. 5. All alkylacyl derivatives of CoA tested activated Bacillus pyruvate carboxylase; acetyl-CoA was the most effective. The apparent K(a) exhibited a biphasic relationship with acyl-chain length for the straight-chain homologues. Certain long-chain acyl-CoA species showed additional activation at a high concentration. Weak activation occurred on addition of CoA or adenosine 3',5'-bisphosphate, but carboxyacyl-CoA species and derivatives containing a modified phosphoadenosyl group were inhibitory. Thioesters of CoA with non-carboxylic acids, e.g. methanesulphonyl-CoA, serve as activators of the thermophilic Bacillus and Saccharomyces cerevisiae pyruvate carboxylases, but as inhibitors of pyruvate carboxylases obtained from chicken and rat liver. 6. alpha-Oxoglutarate mimics the effect of l-aspartate as a regulatory inhibitor of the pyruvate carboxylases from both the thermophilic Bacillus and Saccharomyces cerevisiae. l-Glutamate was ineffective in both cases.", "contents": "Pyruvate carboxylase from a thermophilic Bacillus. Studies on the specificity of activation by acyl derivatives of coenzyme A and on the properties of catalysis in the absence of activator. 1. Oxaloacetate synthesis catalysed by pyruvate carboxylase from a thermophilic Bacillus in the absence of acetyl-CoA required addition of high concentrations of pyruvate, MgATP(2-) and HCO(3) (-), and at 45 degrees C occurred at a maximum rate approx. 20% of that in the presence of a saturating concentration of acetyl-CoA. The apparent K(m) for HCO(3) (-) at pH7.8 was 400mm without acetyl-CoA, and 16mm with a saturating activator concentration. The relationship between reciprocal initial rate and reciprocal MgATP(2-) concentration was non-linear (convex-down) in the absence of acetyl-CoA, but the extent of deviation decreased as the activator concentration was increased. The relationship between reciprocal initial rate and reciprocal pyruvate concentration was non-linear (convex-down) in the presence or absence of acetyl-CoA. 2. The optimum pH for catalysis of oxaloacetate synthesis was similar in the presence or absence of acetyl-CoA. The variation with pH of apparent K(m) for HCO(3) (-) implicated residue(s) with pK(a) 8.6 in catalysis of the activator-independent oxaloacetate synthesis. 3. Linear Arrhenius and van't Hoff plots were observed for the temperature-dependence of oxaloacetate synthesis in the absence of acetyl-CoA over the range 25-55 degrees C. E(a) (activation energy) was 56.3kJ/mol and DeltaH(double dagger) (HCO(3) (-)) (enthalpy of activation) was -38.6kJ/mol. In the presence of acetyl-CoA, biphasic Arrhenius and van't Hoff plots are observed with a change of slope at 30 degrees C in each case. E(a) was 43.7 and 106.3kJ/mol above and below 30 degrees C respectively. 4. Incubation of Bacillus pyruvate carboxylase with trinitrobenzenesulphonate caused specific inactivation of acetyl-CoA-dependent catalytic activity associated with the incorporation of 1.3+/-0.2 trinitrophenyl residues per subunit. Activator-independent catalysis and regulatory inhibition by l-aspartate were unaffected. The rate of inactivation of acetyl-CoA-dependent catalysis by trinitrobenzenesulphonate was specifically decreased by addition of acetyl-CoA and other acetyl-CoA and other acyl-CoA species, but complete protection was not obtained. 5. All alkylacyl derivatives of CoA tested activated Bacillus pyruvate carboxylase; acetyl-CoA was the most effective. The apparent K(a) exhibited a biphasic relationship with acyl-chain length for the straight-chain homologues. Certain long-chain acyl-CoA species showed additional activation at a high concentration. Weak activation occurred on addition of CoA or adenosine 3',5'-bisphosphate, but carboxyacyl-CoA species and derivatives containing a modified phosphoadenosyl group were inhibitory. Thioesters of CoA with non-carboxylic acids, e.g. methanesulphonyl-CoA, serve as activators of the thermophilic Bacillus and Saccharomyces cerevisiae pyruvate carboxylases, but as inhibitors of pyruvate carboxylases obtained from chicken and rat liver. 6. alpha-Oxoglutarate mimics the effect of l-aspartate as a regulatory inhibitor of the pyruvate carboxylases from both the thermophilic Bacillus and Saccharomyces cerevisiae. l-Glutamate was ineffective in both cases."}
{"id": "PMID:25649", "title": "The isolation and properties of a non-pepsin proteinase from human gastric mucosa.", "content": "1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D.", "contents": "The isolation and properties of a non-pepsin proteinase from human gastric mucosa. 1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D."}
{"id": "PMID:25650", "title": "The biochemical pathway for the breakdown of N4-ethyl-L-asparagine in the bacterium Pseudomonas stutzeri.", "content": "N4-Ethyl-L-[u-14C]asparagine and L-[U-14C]aspartate give identical metabolites, mainly intermediates of the tricarboxylic acid cycle and related amino acids, in whole cells of Pseudomonas stutzeri. The labelled asparagine derivative is converted into [14C]-aspartate by cell-free extracts, and this reaction, which has an optimum pH of 8.8 +/- 0.2, is neither inhibited by unlabelled asparagine nor enhanced by unlabelled 2-oxoglutarate. No labelled keto acid corresponding to N4-ethylasparagine was detected in either whole cells or cell-free extracts. Thus N4-ethyl-L-asparagine, like asparagine, must be broken down by hydrolysis, at least in this bacterium.", "contents": "The biochemical pathway for the breakdown of N4-ethyl-L-asparagine in the bacterium Pseudomonas stutzeri. N4-Ethyl-L-[u-14C]asparagine and L-[U-14C]aspartate give identical metabolites, mainly intermediates of the tricarboxylic acid cycle and related amino acids, in whole cells of Pseudomonas stutzeri. The labelled asparagine derivative is converted into [14C]-aspartate by cell-free extracts, and this reaction, which has an optimum pH of 8.8 +/- 0.2, is neither inhibited by unlabelled asparagine nor enhanced by unlabelled 2-oxoglutarate. No labelled keto acid corresponding to N4-ethylasparagine was detected in either whole cells or cell-free extracts. Thus N4-ethyl-L-asparagine, like asparagine, must be broken down by hydrolysis, at least in this bacterium."}
{"id": "PMID:25651", "title": "The microbial metabolism of Cl compounds. The stoicheiometry of respiration-driven proton translocation in Pseudomonas AM1 and in a mutant lacking cytochrome c.", "content": "This paper clarifies the role of cytochrome c in Pseudomonas AM1 by measuring the stoicheiometry of proton translocation driven by respiration of endogenous or added substrates in wild-type bacteria and in a mutant lacking cytochrome c (mutant PCT76). The maximum -->H(+)/O ratio (protons translocated out of the bacteria per atom of oxygen consumed during respiration) was about 4 and, except when respiration was markedly affected, this ratio was similar in mutant and wild-type bacteria. The -->H(+)/O ratios were unaltered when the usual oxidase (cytochrome a(3)) was inhibited by 300mum-KCN and respiration involved the single cytochrome b functioning as an alternative oxidase. Ratios measured in cells respiring endogenous substrate and in cells loaded with malate or 3-hydroxybutyrate suggest that there are two proton-translocating segments operating during the oxidation of NADH. By contrast, during oxidation of formaldehyde or methylamine only one pair of protons is translocated. Proton translocation could not be measured with methanol as substrate, because its oxidation was inhibited (90-95%) by 5mm-KSCN. It is tentatively proposed that the electron-transport chain for NADH oxidation in Pseudomonas AM1 is arranged such that the NADH-ubiquinone oxidoreductase forms one proton-translocating segment and the second segment consists of ubiquinone and cytochromes b and a/a(3). The cytochrome c appears to be essential only for respiration and proton translocation from methanol (and possibly from methylamine); there is no conclusive evidence that cytochrome c ever mediates between cytochromes b and a/a(3) in Pseudomonas AM1.", "contents": "The microbial metabolism of Cl compounds. The stoicheiometry of respiration-driven proton translocation in Pseudomonas AM1 and in a mutant lacking cytochrome c. This paper clarifies the role of cytochrome c in Pseudomonas AM1 by measuring the stoicheiometry of proton translocation driven by respiration of endogenous or added substrates in wild-type bacteria and in a mutant lacking cytochrome c (mutant PCT76). The maximum -->H(+)/O ratio (protons translocated out of the bacteria per atom of oxygen consumed during respiration) was about 4 and, except when respiration was markedly affected, this ratio was similar in mutant and wild-type bacteria. The -->H(+)/O ratios were unaltered when the usual oxidase (cytochrome a(3)) was inhibited by 300mum-KCN and respiration involved the single cytochrome b functioning as an alternative oxidase. Ratios measured in cells respiring endogenous substrate and in cells loaded with malate or 3-hydroxybutyrate suggest that there are two proton-translocating segments operating during the oxidation of NADH. By contrast, during oxidation of formaldehyde or methylamine only one pair of protons is translocated. Proton translocation could not be measured with methanol as substrate, because its oxidation was inhibited (90-95%) by 5mm-KSCN. It is tentatively proposed that the electron-transport chain for NADH oxidation in Pseudomonas AM1 is arranged such that the NADH-ubiquinone oxidoreductase forms one proton-translocating segment and the second segment consists of ubiquinone and cytochromes b and a/a(3). The cytochrome c appears to be essential only for respiration and proton translocation from methanol (and possibly from methylamine); there is no conclusive evidence that cytochrome c ever mediates between cytochromes b and a/a(3) in Pseudomonas AM1."}
{"id": "PMID:25652", "title": "Regulation of the oxidative phase of the pentose phosphate cycle in mussels.", "content": "1. The mechanisms that control the oxidative phase of the pentose phosphate cycle in mussel hepatopancreas were investigated. 2. The effects of GSSG (oxidized glutathione) on the inhibition of glucose 6-phosphate dehydrogenase by NADPH [Eggleston & Krebs (1974) Biochem. J. 138, 425-435] extend to 6-phosphogluconate dehydrogenase. 3. The effect of GSSG on both enzymes increases as the [NADP+1]/[NADPH] ratio decreases; greater percentage deinhibition always was obtained for 6-phosphogluconate dehydrogenase. 4. Increasing concentration of GSSG increased the percentage deinhibition. This effect is more pronounced with 6-phosphogluconate dehydrogenase. 5. We confirmed the apparent imbalance between the activities of the two enzymes [sapag-Hagar, Lagunas & Sols (1973) Biochem. Biophys. Res. Commun, 50, 179-185] in the presence of 10mM-Mg2+. 6. The imbalance practically disappears when the substrate concentrations are less than saturating and Mg2+ approaches physiological concentrations. 7. The addition of GSSG at physiological concentrations allows the activities of both enzymes to be measured at high [NADPH]/[NADP+] ratios ratios and the co-operative action of GSSG and Mg2+ on the imbalance between the two enzymes to be verified. 8. The control of the activity of the two enzymes of the pentose cycle could be carried out by deinhibition of the two dehydrogenases and by the intracellular concentrations of substrates and inorganic ions.", "contents": "Regulation of the oxidative phase of the pentose phosphate cycle in mussels. 1. The mechanisms that control the oxidative phase of the pentose phosphate cycle in mussel hepatopancreas were investigated. 2. The effects of GSSG (oxidized glutathione) on the inhibition of glucose 6-phosphate dehydrogenase by NADPH [Eggleston & Krebs (1974) Biochem. J. 138, 425-435] extend to 6-phosphogluconate dehydrogenase. 3. The effect of GSSG on both enzymes increases as the [NADP+1]/[NADPH] ratio decreases; greater percentage deinhibition always was obtained for 6-phosphogluconate dehydrogenase. 4. Increasing concentration of GSSG increased the percentage deinhibition. This effect is more pronounced with 6-phosphogluconate dehydrogenase. 5. We confirmed the apparent imbalance between the activities of the two enzymes [sapag-Hagar, Lagunas & Sols (1973) Biochem. Biophys. Res. Commun, 50, 179-185] in the presence of 10mM-Mg2+. 6. The imbalance practically disappears when the substrate concentrations are less than saturating and Mg2+ approaches physiological concentrations. 7. The addition of GSSG at physiological concentrations allows the activities of both enzymes to be measured at high [NADPH]/[NADP+] ratios ratios and the co-operative action of GSSG and Mg2+ on the imbalance between the two enzymes to be verified. 8. The control of the activity of the two enzymes of the pentose cycle could be carried out by deinhibition of the two dehydrogenases and by the intracellular concentrations of substrates and inorganic ions."}
{"id": "PMID:25653", "title": "Proton translocation of the bovine chromaffin-granule membrane.", "content": "Bovine chromaffin granules were lysed and their membranes resealed to give osmotically sensitive 'ghosts'. These swell in the presence of salts and MgATP. It is shown that this is due to proton entry accompanied by anions. The rate of swelling depends on the anion present, but swelling is not limited to media containing permeant anions. It is quite marked in solutions of sulphates, phosphates and acetates. It is not uncoupler-sensitive, suggesting that at least one component of swelling is due to coupled proton and anion entry (non-electrogenic proton translocation). Direct measurements of transmembrane pH and potential gradients generated in the presence of MgATP shows that these are rapidly established in sucrose media, and are rather little affected by the presence of salts. They contribute roughly equally to the total protonmotive force. The potential gradient is establihsed very rapidly, but the pH gradient is generated over several minutes. The gradients are not completely dissipated by uncoupler, and it is shown that, in media containing sulphate but no permeant anion, sulphate can be taken up by the 'ghosts'. There thus appear to be two mechanisms of proton translocation across the membrane, both dependent on ATP hydrolysis: an electrogenic transfer of protons, and proton movement linked to an anion transporter of broad specificity.", "contents": "Proton translocation of the bovine chromaffin-granule membrane. Bovine chromaffin granules were lysed and their membranes resealed to give osmotically sensitive 'ghosts'. These swell in the presence of salts and MgATP. It is shown that this is due to proton entry accompanied by anions. The rate of swelling depends on the anion present, but swelling is not limited to media containing permeant anions. It is quite marked in solutions of sulphates, phosphates and acetates. It is not uncoupler-sensitive, suggesting that at least one component of swelling is due to coupled proton and anion entry (non-electrogenic proton translocation). Direct measurements of transmembrane pH and potential gradients generated in the presence of MgATP shows that these are rapidly established in sucrose media, and are rather little affected by the presence of salts. They contribute roughly equally to the total protonmotive force. The potential gradient is establihsed very rapidly, but the pH gradient is generated over several minutes. The gradients are not completely dissipated by uncoupler, and it is shown that, in media containing sulphate but no permeant anion, sulphate can be taken up by the 'ghosts'. There thus appear to be two mechanisms of proton translocation across the membrane, both dependent on ATP hydrolysis: an electrogenic transfer of protons, and proton movement linked to an anion transporter of broad specificity."}
{"id": "PMID:25654", "title": "Hydroxytryptamine transport by the bovine chromaffin-granule membrane.", "content": "5-Hydroxytryptamine is accumulated by resealed chromaffin-granule 'ghosts' if a pH gradient (acid inside) is imposed across their membranes by preincubating them at low pH. This uptake, like that driven by MgATP, is reserpine- and uncoupler-sensitive. This strongly suggests that catecholamines are taken up by intact granules in response to a pH gradient. In line with this, it is shown that 5-hydroxytryptamine decreases the pH gradient generated in the presence of MgATP, an effect that is inhibited by reserpine; nigericin, which discharges the pH gradient in the presence of K+, inhibits uptake. Permeant anions, however, also inhibit uptake. It is suggested that this may be because they permit equilibration of amine cations directly across the membrane, down concentration gradients.", "contents": "Hydroxytryptamine transport by the bovine chromaffin-granule membrane. 5-Hydroxytryptamine is accumulated by resealed chromaffin-granule 'ghosts' if a pH gradient (acid inside) is imposed across their membranes by preincubating them at low pH. This uptake, like that driven by MgATP, is reserpine- and uncoupler-sensitive. This strongly suggests that catecholamines are taken up by intact granules in response to a pH gradient. In line with this, it is shown that 5-hydroxytryptamine decreases the pH gradient generated in the presence of MgATP, an effect that is inhibited by reserpine; nigericin, which discharges the pH gradient in the presence of K+, inhibits uptake. Permeant anions, however, also inhibit uptake. It is suggested that this may be because they permit equilibration of amine cations directly across the membrane, down concentration gradients."}
{"id": "PMID:25655", "title": "Contribution of cytochromes and proteins to the effect of ascorbic acid on artificial and microsomal hydroxylation systems containing oxygen and hydrogen peroxide.", "content": "Hydroxylation systems containing cytochromes, proteins and ascorbic acid were studied at physiological pH (7.4) under O2 or N2 with added H2O2. Proteins inhibited aromatic hydroxylation of p-nitrophenol or oxidative demethylation of ethylmorphine in ascorbic acid-containing systems incubated under O2, but strongly activated the systems containing H2O2. Cytochrome c and partially purified cytochrome P-450 from rat liver microsomal preparations activated the system in either O2 or H2O2. The systems needed ascorbic acid (or other enol structures) for activation. Cytochrome iron participated probably in the activation of O2, whereas cytochrome protein participated in a free radical activation of H2O2 (or of O2).", "contents": "Contribution of cytochromes and proteins to the effect of ascorbic acid on artificial and microsomal hydroxylation systems containing oxygen and hydrogen peroxide. Hydroxylation systems containing cytochromes, proteins and ascorbic acid were studied at physiological pH (7.4) under O2 or N2 with added H2O2. Proteins inhibited aromatic hydroxylation of p-nitrophenol or oxidative demethylation of ethylmorphine in ascorbic acid-containing systems incubated under O2, but strongly activated the systems containing H2O2. Cytochrome c and partially purified cytochrome P-450 from rat liver microsomal preparations activated the system in either O2 or H2O2. The systems needed ascorbic acid (or other enol structures) for activation. Cytochrome iron participated probably in the activation of O2, whereas cytochrome protein participated in a free radical activation of H2O2 (or of O2)."}
{"id": "PMID:25656", "title": "Evidence for a pH-dependent irreversible formation of a stable conformation of phenacyl-alpha-chymotrypsin.", "content": "A reinvestigation of the modification reactions of alpha-chymotrypsin with phenacyl bromide was carried out. Results conclusively demonstrate that the chemically and physically different modified enzymes prepared at pH 4 and at pH 7 both contain the phenacyl group at methionine-192 in the sulphonium salt form. Evidence to suppoort this conclusion derives from 13C nuclear-magnetic-resonance spectroscopic observations on [methylene-13C]phenacyl-enriched enzymes. More conclusively, the methionine-192-containing C-chain, derived by performic acid oxidative cleavage of radioactively-labelled enzyme prepared at pH 7, was shown to contain the phenacyl moiety and to undergo dealkylation by 2-mercaptoethanol with loss of this moiety. In addition, thermolytic cleavage of the high-pH enzyme results in fragmentation of the polypeptide chain in a fashion analogous to model reactions of phenacylmethionyl dipeptides and other methionine-192 sulphonium salts. A rationalization of the unusual nature of the high-pH phenacyl-modified enzyme based on the irreversible formation of stable conformation in which the phenacyl moiety is rigidly located in interior regions of the enzyme is presented and discussed.", "contents": "Evidence for a pH-dependent irreversible formation of a stable conformation of phenacyl-alpha-chymotrypsin. A reinvestigation of the modification reactions of alpha-chymotrypsin with phenacyl bromide was carried out. Results conclusively demonstrate that the chemically and physically different modified enzymes prepared at pH 4 and at pH 7 both contain the phenacyl group at methionine-192 in the sulphonium salt form. Evidence to suppoort this conclusion derives from 13C nuclear-magnetic-resonance spectroscopic observations on [methylene-13C]phenacyl-enriched enzymes. More conclusively, the methionine-192-containing C-chain, derived by performic acid oxidative cleavage of radioactively-labelled enzyme prepared at pH 7, was shown to contain the phenacyl moiety and to undergo dealkylation by 2-mercaptoethanol with loss of this moiety. In addition, thermolytic cleavage of the high-pH enzyme results in fragmentation of the polypeptide chain in a fashion analogous to model reactions of phenacylmethionyl dipeptides and other methionine-192 sulphonium salts. A rationalization of the unusual nature of the high-pH phenacyl-modified enzyme based on the irreversible formation of stable conformation in which the phenacyl moiety is rigidly located in interior regions of the enzyme is presented and discussed."}
{"id": "PMID:25657", "title": "Pressure relaxation of the equilibrium of the pig heart lactate dehydrogenase system.", "content": "The relaxation behaviour of a system of reactants equilibrated in the presence of pig heart lactate dehydrogenase was studied after pressure perturbation. Two relaxations were observed when protein fluorescence was recorded, but only the slower relaxation was apparent in observations of A340. The faster relaxation therefore involves transfer between free and enzyme-bound NADH, whereas the slower relaxation represents the reduction of NAD+. Both relaxations were observed in Tris buffer, where there is little effect of pressure on pH, and in phosphate buffer, where pH changes are significant; however, the amplitudes depended on the buffer used. The slower reciprocal relaxation time increases with increasing total enzyme concentration and decreases slightly with increasing NAD+ concentration. Computer simulations, based on a proposed mechanism, were compared with the experimentally determined amplitudes and relaxation times as a test of the mechanism.", "contents": "Pressure relaxation of the equilibrium of the pig heart lactate dehydrogenase system. The relaxation behaviour of a system of reactants equilibrated in the presence of pig heart lactate dehydrogenase was studied after pressure perturbation. Two relaxations were observed when protein fluorescence was recorded, but only the slower relaxation was apparent in observations of A340. The faster relaxation therefore involves transfer between free and enzyme-bound NADH, whereas the slower relaxation represents the reduction of NAD+. Both relaxations were observed in Tris buffer, where there is little effect of pressure on pH, and in phosphate buffer, where pH changes are significant; however, the amplitudes depended on the buffer used. The slower reciprocal relaxation time increases with increasing total enzyme concentration and decreases slightly with increasing NAD+ concentration. Computer simulations, based on a proposed mechanism, were compared with the experimentally determined amplitudes and relaxation times as a test of the mechanism."}
{"id": "PMID:25658", "title": "Pyruvate-to-ethanol pathway in Entamoeba histolytica.", "content": "The pyruvate-to-ethanol pathway in Entamoeba histolytica is unusual when compared with most investigated organisms. Pyruvate decarboxylase (EC 4.1.1.1), a key enzyme for ethanol production, is not found. Pyruvate is converted into acetyl-CoA and CO2 by the enzyme pyruvate synthase (EC 1.2.7.1), which has been demonstrated previously in this parasitic amoeba. Acetyl-CoA is reduced to acetaldehyde and CoA by the enzyme aldehyde dehydrogenase (acylating) (EC 1.2.1.10) at an enzyme activity of 9 units per g of fresh cells with NADH as a reductant. Acetaldehyde is further reduced by either a previously identified NADP+-linked alcohol dehydrogenase or by a newly found NAD+-linked alcohol dehydrogenase at an enzyme activity of 136 units per g of fresh cells. Ethanol is identified as the product of soluble enzymes of amoeba acting on pyruvate or acetyl-CoA. This result is confirmed by radioactive isotopic, spectrophotometric and gas-chromatographic methods.", "contents": "Pyruvate-to-ethanol pathway in Entamoeba histolytica. The pyruvate-to-ethanol pathway in Entamoeba histolytica is unusual when compared with most investigated organisms. Pyruvate decarboxylase (EC 4.1.1.1), a key enzyme for ethanol production, is not found. Pyruvate is converted into acetyl-CoA and CO2 by the enzyme pyruvate synthase (EC 1.2.7.1), which has been demonstrated previously in this parasitic amoeba. Acetyl-CoA is reduced to acetaldehyde and CoA by the enzyme aldehyde dehydrogenase (acylating) (EC 1.2.1.10) at an enzyme activity of 9 units per g of fresh cells with NADH as a reductant. Acetaldehyde is further reduced by either a previously identified NADP+-linked alcohol dehydrogenase or by a newly found NAD+-linked alcohol dehydrogenase at an enzyme activity of 136 units per g of fresh cells. Ethanol is identified as the product of soluble enzymes of amoeba acting on pyruvate or acetyl-CoA. This result is confirmed by radioactive isotopic, spectrophotometric and gas-chromatographic methods."}
{"id": "PMID:25659", "title": "DNA polymerases from Chlamydomonas reinhardii. Purification and properties.", "content": "Three DNA polymerase activities, A, B and C, were identified in extracts of exponentially growing synchronous cultures of Chlamydomonas reinhardii, and DNA polymerases A and B were characterized in detail. Both enzymes have the same binding affinity for DEAE-cellulose at pH 7.8, but can be distinguished from each other by their behaviour on phosphocellulose and DNA-agarose. 'Activated' calf thymus DNA was used as template, and the pH, K+ and bivalent-cation optima were measured. DNA polymerase A sediments at 5.3 S in glycerol gradients, with an apparent mol.wt. of 90000-100000. Polymerase B sediments between 8S and 10S in 100mM-KCl, the predominant species having an apparent mol.wt. of 200000. In 200mM-KCl, polymerase B dissociates to a single species, which sediments at 5.8S. A 3S species was found in aged preparations of both enzymes. The activity of polymerase B from cells harvested during nuclear DNA synthesis is twice that found in Chlamydomonas at other times during the cell cycle.", "contents": "DNA polymerases from Chlamydomonas reinhardii. Purification and properties. Three DNA polymerase activities, A, B and C, were identified in extracts of exponentially growing synchronous cultures of Chlamydomonas reinhardii, and DNA polymerases A and B were characterized in detail. Both enzymes have the same binding affinity for DEAE-cellulose at pH 7.8, but can be distinguished from each other by their behaviour on phosphocellulose and DNA-agarose. 'Activated' calf thymus DNA was used as template, and the pH, K+ and bivalent-cation optima were measured. DNA polymerase A sediments at 5.3 S in glycerol gradients, with an apparent mol.wt. of 90000-100000. Polymerase B sediments between 8S and 10S in 100mM-KCl, the predominant species having an apparent mol.wt. of 200000. In 200mM-KCl, polymerase B dissociates to a single species, which sediments at 5.8S. A 3S species was found in aged preparations of both enzymes. The activity of polymerase B from cells harvested during nuclear DNA synthesis is twice that found in Chlamydomonas at other times during the cell cycle."}
{"id": "PMID:25660", "title": "The purification and properties of urocanase from Pseudomonas testosteroni.", "content": "Urocanase (urocanate hydratase, EC 4.2.1.49) purified from Pseudomonas testosteroni has a mol.wt. of 118000 determined by sedimentation-equilibrium analysis. Ultracentrifugation in 6M-guanidine hydrochloride and polyacrylamide-gel electrophoresis in sodium dodecyl sulphate show that the enzyme consists of two identical or very similar subunits. It is, like urocanase isolated from other sources, inhibited by reagents that react with carbonyl groups. Although urocanase from Ps. testosteroni is strongly inhibited by NaBH4, no evidence could be obtained for the presence of covalently bound 2-oxobutyrate as a prosthetic group; this is in contrast with findings elsewhere for urocanase from Pseudomonas putida. Urocanase from Ps. testosteroni does not contain pyridoxal 5'-phosphate as a coenzyme and in this respect is similar to all urocanases studied in purified form.", "contents": "The purification and properties of urocanase from Pseudomonas testosteroni. Urocanase (urocanate hydratase, EC 4.2.1.49) purified from Pseudomonas testosteroni has a mol.wt. of 118000 determined by sedimentation-equilibrium analysis. Ultracentrifugation in 6M-guanidine hydrochloride and polyacrylamide-gel electrophoresis in sodium dodecyl sulphate show that the enzyme consists of two identical or very similar subunits. It is, like urocanase isolated from other sources, inhibited by reagents that react with carbonyl groups. Although urocanase from Ps. testosteroni is strongly inhibited by NaBH4, no evidence could be obtained for the presence of covalently bound 2-oxobutyrate as a prosthetic group; this is in contrast with findings elsewhere for urocanase from Pseudomonas putida. Urocanase from Ps. testosteroni does not contain pyridoxal 5'-phosphate as a coenzyme and in this respect is similar to all urocanases studied in purified form."}
{"id": "PMID:25661", "title": "A reappraisal of the reaction of butyryl-coenzyme A dehydrogenase with phenylmercuric acetate. Evidence that de-greening involves a reaction of the tightly bound thioester.", "content": "Phenylmercuric acetate reversibly de-greens butyryl-CoA dehydrogenase from Megasphaera elsdenii, abolishing the absorption band at 710nm. The view that this is a result of modification of a protein thiol group is re-examined in the light of the following new observations. (i) After treatment with phenylmercuric acetate, the enzyme's ability to be re-greened by addition of thiols was not decreased by gel filtration or precipitation with (NH(4))(2)SO(4). (ii) Phenylmercuric acetate caused the same extent of de-greening whether added in a few large amounts or many small ones. The overall time taken for de-greening was, however, greatly extended when many small additions were made. (iii) In Tris/acetate buffer, pH7.5, 3.5mol of phenylmercuric acetate/mol of enzyme subunit was required for complete de-greening, compared with only 2.5mol/mol in phosphate buffer, pH7. (iv) None of the groups that react with phenylmercuric acetate is accessible to iodoacetate or iodoacetamide. (v) On a molar basis dithiothreitol, mercaptoethanol and CoA are equally effective in re-greening the enzyme. (vi) Provided that phenylmercuric acetate is not present in excess, the de-greened enzyme forms normal and stable complexes with crotonyl-CoA and acetoacetyl-CoA. (vii) When a small excess of phenylmercuric acetate is present, full stable development of the enzyme-acetoacetyl-CoA complex requires addition of several mol of acetoacetyl-CoA/mol of enzyme subunit. (viii) The ability of de-greened enzyme to be immediately re-greened by an excess of thiol declines with time, more rapidly at pH6 than at pH7 or 8, but at all three pH values the instantaneous re-greening was followed by a slow phase of further increase in A(710). This further recovery was most extensive and most rapid at pH8. These findings are reminiscent of the previously described reversible decline in the re-greening capacity of a protein-free acid extract of green butyryl-CoA dehydrogenase. It is concluded that the likely cause of de-greening is chemical modification of the tightly bound thioester rather than a protein thiol group. The reversibility would be explained if the thioester exists on the surface of the enzyme in equilibrium with free CoA and a lactone, or if the acyl group is readily and reversibly transferred from the thiol of CoA to a protein side chain.", "contents": "A reappraisal of the reaction of butyryl-coenzyme A dehydrogenase with phenylmercuric acetate. Evidence that de-greening involves a reaction of the tightly bound thioester. Phenylmercuric acetate reversibly de-greens butyryl-CoA dehydrogenase from Megasphaera elsdenii, abolishing the absorption band at 710nm. The view that this is a result of modification of a protein thiol group is re-examined in the light of the following new observations. (i) After treatment with phenylmercuric acetate, the enzyme's ability to be re-greened by addition of thiols was not decreased by gel filtration or precipitation with (NH(4))(2)SO(4). (ii) Phenylmercuric acetate caused the same extent of de-greening whether added in a few large amounts or many small ones. The overall time taken for de-greening was, however, greatly extended when many small additions were made. (iii) In Tris/acetate buffer, pH7.5, 3.5mol of phenylmercuric acetate/mol of enzyme subunit was required for complete de-greening, compared with only 2.5mol/mol in phosphate buffer, pH7. (iv) None of the groups that react with phenylmercuric acetate is accessible to iodoacetate or iodoacetamide. (v) On a molar basis dithiothreitol, mercaptoethanol and CoA are equally effective in re-greening the enzyme. (vi) Provided that phenylmercuric acetate is not present in excess, the de-greened enzyme forms normal and stable complexes with crotonyl-CoA and acetoacetyl-CoA. (vii) When a small excess of phenylmercuric acetate is present, full stable development of the enzyme-acetoacetyl-CoA complex requires addition of several mol of acetoacetyl-CoA/mol of enzyme subunit. (viii) The ability of de-greened enzyme to be immediately re-greened by an excess of thiol declines with time, more rapidly at pH6 than at pH7 or 8, but at all three pH values the instantaneous re-greening was followed by a slow phase of further increase in A(710). This further recovery was most extensive and most rapid at pH8. These findings are reminiscent of the previously described reversible decline in the re-greening capacity of a protein-free acid extract of green butyryl-CoA dehydrogenase. It is concluded that the likely cause of de-greening is chemical modification of the tightly bound thioester rather than a protein thiol group. The reversibility would be explained if the thioester exists on the surface of the enzyme in equilibrium with free CoA and a lactone, or if the acyl group is readily and reversibly transferred from the thiol of CoA to a protein side chain."}
{"id": "PMID:25662", "title": "A study of the enhanced toxicity of doxapram in rodents treated with narcotic analgesics.", "content": "It has been shown in both mice and rats that the LD50 value for doxapram is reduced in rodents treated with narcotic analgesics. In both species the site of the toxic interaction appears to be the cardiovascular system. Doxapram alone, in sub-lethal doses, appears to cause conduction defects in the heart and this action of doxapram is increased in rodents treated with morphine. The enhancement of the toxicity of doxapram by morphine appears to involve an action in the central nervous system probably not related to respiratory depression.", "contents": "A study of the enhanced toxicity of doxapram in rodents treated with narcotic analgesics. It has been shown in both mice and rats that the LD50 value for doxapram is reduced in rodents treated with narcotic analgesics. In both species the site of the toxic interaction appears to be the cardiovascular system. Doxapram alone, in sub-lethal doses, appears to cause conduction defects in the heart and this action of doxapram is increased in rodents treated with morphine. The enhancement of the toxicity of doxapram by morphine appears to involve an action in the central nervous system probably not related to respiratory depression."}
{"id": "PMID:25663", "title": "Lorazepam, hyoscine and atropine as i.v. surgical premedicants.", "content": "Lorazepam 2 and 4 mg alone and in combination with atropine 0.4 mg and hyoscine 0.4 mg were studied as i.v. surgical premedicants in 150 patients. Relief of anxiety, sedation, patient acceptance, lack of recall and side-effects were evaluated. Hyoscine was found to improve the relief of anxiety and sedation associated with lorazepam, but did not significantly increase lack of recall or patient acceptance. The addition of atropine to lorazepam did not significantly alter its effects. A high frequency of agitation and restlessness in patients receiving lorazepam and hyoscine make this combination undesirable for surgical premedication.", "contents": "Lorazepam, hyoscine and atropine as i.v. surgical premedicants. Lorazepam 2 and 4 mg alone and in combination with atropine 0.4 mg and hyoscine 0.4 mg were studied as i.v. surgical premedicants in 150 patients. Relief of anxiety, sedation, patient acceptance, lack of recall and side-effects were evaluated. Hyoscine was found to improve the relief of anxiety and sedation associated with lorazepam, but did not significantly increase lack of recall or patient acceptance. The addition of atropine to lorazepam did not significantly alter its effects. A high frequency of agitation and restlessness in patients receiving lorazepam and hyoscine make this combination undesirable for surgical premedication."}
{"id": "PMID:25664", "title": "Exacerbations of chronic bronchitis: exogenous or endogenous infection?", "content": "Six male patients with chronic bronchitis, who were known previously to have excreted Streptococcus pneumoniae and/or Haemophilus influenzae, both at the times of exacerbations and during remission, were studied for 43 to 52 months. Sputum was examined fortnightly and at the time of exacerbations. Strains of Strep. pneumoniae were serotyped and those of Haemophilus species were typed by antibiograms along with other supporting methods. Sera collected before or at the time of an exacerbation and seven and 30 days afterwards were examined by complement fixation tests against respiratory viruses and Mycoplasma pneumoniae. In 18 out of 25 exacerbations there was evidence of a new type of Strep. pneumoniae and/or Haemophilus spp. or of a current virus infection, suggesting exogenous infection in the majority of these cases. There was a possible reason for failure to detect a new pathogen in three of the seven cases in which none was found. In five further exacerbations adequate investigation was not possible.", "contents": "Exacerbations of chronic bronchitis: exogenous or endogenous infection? Six male patients with chronic bronchitis, who were known previously to have excreted Streptococcus pneumoniae and/or Haemophilus influenzae, both at the times of exacerbations and during remission, were studied for 43 to 52 months. Sputum was examined fortnightly and at the time of exacerbations. Strains of Strep. pneumoniae were serotyped and those of Haemophilus species were typed by antibiograms along with other supporting methods. Sera collected before or at the time of an exacerbation and seven and 30 days afterwards were examined by complement fixation tests against respiratory viruses and Mycoplasma pneumoniae. In 18 out of 25 exacerbations there was evidence of a new type of Strep. pneumoniae and/or Haemophilus spp. or of a current virus infection, suggesting exogenous infection in the majority of these cases. There was a possible reason for failure to detect a new pathogen in three of the seven cases in which none was found. In five further exacerbations adequate investigation was not possible."}
{"id": "PMID:25665", "title": "Cell membrane enzymes: L-gamma-glutamyl transpeptidase, leucine aminopeptidase, maltase and trehalase in normal and leukaemic lymphocytes.", "content": "Several cell-membrane enzymes, which serve functions in amino acid and sugar transport, were measured in peripheral blood lymphocytes from chronic B and T lymphocytic disorders, blast cells in acute leukaemias, and in normal lymphocytes from cord blood, peripheral blood of adults, tonsils and bone-marrow plasma cells in myelomatosis. The specific activities of L-gamma-glutamyl transpeptidase, maltase and trehalase were low, as compared with those measured in normal blood lymphocytes, in the acute leukaemias and in the chronic B-cell disorders. In myelomatosis and in the chronic T-cell disorders, the specific activity of these three enzymes was in the normal range or above normal. The specific activity of leucine aminopeptidase was low in all the chronic B-cell disorders and in some of the lymphoblastic leukaemias. It was elevated in S\u00e9zary syndrome cells but low in T-chronic lymphocytic leukaemia. All four enzymes were lower than normal in cord blood lymphocytes and higher than normal in tonsils. These findings are discussed in relation to the patterns of lymphoid cell differentiation and maturation in normal tissues and in leukaemic states.", "contents": "Cell membrane enzymes: L-gamma-glutamyl transpeptidase, leucine aminopeptidase, maltase and trehalase in normal and leukaemic lymphocytes. Several cell-membrane enzymes, which serve functions in amino acid and sugar transport, were measured in peripheral blood lymphocytes from chronic B and T lymphocytic disorders, blast cells in acute leukaemias, and in normal lymphocytes from cord blood, peripheral blood of adults, tonsils and bone-marrow plasma cells in myelomatosis. The specific activities of L-gamma-glutamyl transpeptidase, maltase and trehalase were low, as compared with those measured in normal blood lymphocytes, in the acute leukaemias and in the chronic B-cell disorders. In myelomatosis and in the chronic T-cell disorders, the specific activity of these three enzymes was in the normal range or above normal. The specific activity of leucine aminopeptidase was low in all the chronic B-cell disorders and in some of the lymphoblastic leukaemias. It was elevated in S\u00e9zary syndrome cells but low in T-chronic lymphocytic leukaemia. All four enzymes were lower than normal in cord blood lymphocytes and higher than normal in tonsils. These findings are discussed in relation to the patterns of lymphoid cell differentiation and maturation in normal tissues and in leukaemic states."}
{"id": "PMID:25666", "title": "Characterization of marrow granulocyte development: enzyme-specific activity profiles in response to inflammatory reactions.", "content": "Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose-6-phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals.", "contents": "Characterization of marrow granulocyte development: enzyme-specific activity profiles in response to inflammatory reactions. Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose-6-phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals."}
{"id": "PMID:25668", "title": "Fluorescence-quenching study of glucose binding by yeast hexokinase isoenzymes.", "content": "A study of the effect of varying ionic strength on the glucose-induced quenching of tryptophan fluorescence of hexokinase isoenzymes A(P-I) and B(P-II) was carried out at pH 8.3 and pH 5.5. At p/ 8.3 both isoenzymes gave apparently linear Scatchard-type data plots even with protein concentrations and ionic strengths for which both dimeric and monomeric forms of hexokinase coexist in signiciant amounts. Taking inco account a 1% accuracy in the experimental measurements, we concluded that the intrinsic dissociation constants K(M) and K(D), for the binding of glucose to the monomeric and dimeric forms of HkB, are within a factor of two of each other, i.e. K(D)/K(M) less than or equal to 2. The values of K(M), estimated from the apparent K, were so greatly influenced by ionic strength that it is clear that it is meaningless to compare K(M) and K(D) values measured at different ionic strengths as has been done in the literature. Curvature in the pH 5.5. fluorescence-quenching plots for relatively low ionic strengths demonstrates cooperativity for glucose-binding to the dimer, positive for HkA but negative for HkB. In contrast, the binding is relatively non-cooperative at high ionic strength at this pH. These results were attributed to the well known effect of salt-neutralization of side chain electrical charges on the flexibility and compactness of proteins.", "contents": "Fluorescence-quenching study of glucose binding by yeast hexokinase isoenzymes. A study of the effect of varying ionic strength on the glucose-induced quenching of tryptophan fluorescence of hexokinase isoenzymes A(P-I) and B(P-II) was carried out at pH 8.3 and pH 5.5. At p/ 8.3 both isoenzymes gave apparently linear Scatchard-type data plots even with protein concentrations and ionic strengths for which both dimeric and monomeric forms of hexokinase coexist in signiciant amounts. Taking inco account a 1% accuracy in the experimental measurements, we concluded that the intrinsic dissociation constants K(M) and K(D), for the binding of glucose to the monomeric and dimeric forms of HkB, are within a factor of two of each other, i.e. K(D)/K(M) less than or equal to 2. The values of K(M), estimated from the apparent K, were so greatly influenced by ionic strength that it is clear that it is meaningless to compare K(M) and K(D) values measured at different ionic strengths as has been done in the literature. Curvature in the pH 5.5. fluorescence-quenching plots for relatively low ionic strengths demonstrates cooperativity for glucose-binding to the dimer, positive for HkA but negative for HkB. In contrast, the binding is relatively non-cooperative at high ionic strength at this pH. These results were attributed to the well known effect of salt-neutralization of side chain electrical charges on the flexibility and compactness of proteins."}
{"id": "PMID:25670", "title": "Use of salicylic acid to measure the apparent intracellular pH in the Ehrlich ascites-tumor cell and Escherichia coli.", "content": "The distribution of salicylic acid between the intracellular and extracellular phases has been used to estimate the intracellular pH in the Ehrlich cell and Escherichia coli. The validity of the method was established by: (i) comparison of the results obtained with salicylic acid with those obtained with 5,5-dimethyloxazolidine-2,4-dione; (ii) by following changes of the apparent intracellular pH under circumstances in which such changes are predictable, e.g., the addition of weak acids or proton conductors to the incubation medium during incubation at acidic pH; (iii) by comparison of the apparent intracellular pH changes with the uptake of H+ by the cells estimated from the changes of the medium pH. Optimal results are obtained with this indicator when the extracellular pH is below 5.5, because in this case the indicator is to a sufficient extent in its penetrating form, so that its movement can reflect intracellular pH changes occurring in less than 30 s. When the intracellular pH falls below 5.2 measurable binding of salicylic acid to the intracellular material of the Ehrlich cell takes place, but above this pH no binding has been found. The Ehrlich cell and cells of Escherichia coli behaved similarly under various experimental circumstances tested, but striking difference were found in the inherent permeability of the membrane to H+ and in the changes in this parameter by lowering the temperature to 2 degrees C.", "contents": "Use of salicylic acid to measure the apparent intracellular pH in the Ehrlich ascites-tumor cell and Escherichia coli. The distribution of salicylic acid between the intracellular and extracellular phases has been used to estimate the intracellular pH in the Ehrlich cell and Escherichia coli. The validity of the method was established by: (i) comparison of the results obtained with salicylic acid with those obtained with 5,5-dimethyloxazolidine-2,4-dione; (ii) by following changes of the apparent intracellular pH under circumstances in which such changes are predictable, e.g., the addition of weak acids or proton conductors to the incubation medium during incubation at acidic pH; (iii) by comparison of the apparent intracellular pH changes with the uptake of H+ by the cells estimated from the changes of the medium pH. Optimal results are obtained with this indicator when the extracellular pH is below 5.5, because in this case the indicator is to a sufficient extent in its penetrating form, so that its movement can reflect intracellular pH changes occurring in less than 30 s. When the intracellular pH falls below 5.2 measurable binding of salicylic acid to the intracellular material of the Ehrlich cell takes place, but above this pH no binding has been found. The Ehrlich cell and cells of Escherichia coli behaved similarly under various experimental circumstances tested, but striking difference were found in the inherent permeability of the membrane to H+ and in the changes in this parameter by lowering the temperature to 2 degrees C."}
{"id": "PMID:25674", "title": "Complexes of cobalt (II) and manganese (II) with adenosine 5'-diphosphate and adenosine 5'-triphosphate. A circular dichroism study.", "content": "For studies of interactions between Co2+ and adenosine 5'-diphosphate or adenosine 5'-triphosphate (ADPH4+ and ATPH5+ in strongly acidic medium) visible circular dichroism (d-d transitions of Co2+) and ultraviolet circular dichroism (adenine transitions) have proven to be very sensitive to structural changes. Drastic variation of spectra as a function of pH and concentration enabled us to show the existence of various species, to state their stoichiometry and eventually, their self-association. With ATPH22-, C.D. results are in agreement with recent N.M.R. results. With ligands bearing three negative charges, complexes (1 metal:2 nucleotides)n are formed in which bases of the two nucleotides of the molecule are self-associated. With ADP3-, the visible C.D. spectrum of this complex is intense and hides the spectra of the complexes formed with other protonated species of ADP; this self-associated complex is detected up to a lower limit of 5 X 10(-4) M concentration. With ATPH3-, a complex exhibiting the same characteristics as the one with ADP3- is formed but in about twenty times less amount which explains why it was not detected by potentiometry. With 0.1 M ATP4-, dimeric (or polymeric) complexes, of 1:2 and 1:1 stoichiometry are observed. With 0.01 M ATP4-, 1:1 monomeric and 2:1 dimeric (or polymeric) complexes are detected. The interactions between Mn2+ ions and ADP or ATP have been studied by C.D. on the UV range. The same species as with Co2+ ions have been found but the 1:2 complex formation with ADP3- was shown to occur to a lesser extent and was not observed below a 10(-2) M ADP concentration.", "contents": "Complexes of cobalt (II) and manganese (II) with adenosine 5'-diphosphate and adenosine 5'-triphosphate. A circular dichroism study. For studies of interactions between Co2+ and adenosine 5'-diphosphate or adenosine 5'-triphosphate (ADPH4+ and ATPH5+ in strongly acidic medium) visible circular dichroism (d-d transitions of Co2+) and ultraviolet circular dichroism (adenine transitions) have proven to be very sensitive to structural changes. Drastic variation of spectra as a function of pH and concentration enabled us to show the existence of various species, to state their stoichiometry and eventually, their self-association. With ATPH22-, C.D. results are in agreement with recent N.M.R. results. With ligands bearing three negative charges, complexes (1 metal:2 nucleotides)n are formed in which bases of the two nucleotides of the molecule are self-associated. With ADP3-, the visible C.D. spectrum of this complex is intense and hides the spectra of the complexes formed with other protonated species of ADP; this self-associated complex is detected up to a lower limit of 5 X 10(-4) M concentration. With ATPH3-, a complex exhibiting the same characteristics as the one with ADP3- is formed but in about twenty times less amount which explains why it was not detected by potentiometry. With 0.1 M ATP4-, dimeric (or polymeric) complexes, of 1:2 and 1:1 stoichiometry are observed. With 0.01 M ATP4-, 1:1 monomeric and 2:1 dimeric (or polymeric) complexes are detected. The interactions between Mn2+ ions and ADP or ATP have been studied by C.D. on the UV range. The same species as with Co2+ ions have been found but the 1:2 complex formation with ADP3- was shown to occur to a lesser extent and was not observed below a 10(-2) M ADP concentration."}
{"id": "PMID:25671", "title": "[Reaction between polycytidylic acid and guanosine-5'-triphosphate at neural pH].", "content": "The effect of changing the solution acidity in the interval of pH 7--8 on complex formation between polycytidilyc acid (polyC) and guanosine-5'-triphosphate (GTP) has been studied by the equilibrium dialysis and hydrogen ion titration methods. It is shown that in 1 M NaCl at 3 degrees C the complex stoichiometry undergoes changes in a narrow pH interval being equal to 2 poly C: 1 GTP at pH 7,0--7,3 and to 1 poly C:1 GTP at pH 7,6--8,0. In the presence of GTP the apparent pK of poly C protonation increases by 1,4 PK units and becomes equal to 7,1 in 1 M NaCl at 3 degrees C. Thus, the protonated poly-C takes part in the three-stranded poly-C--GTP complex formation. According to Hill's model of cooperative linear adsorption it is shown that the cooperativity of the three-stranded complex formation is greater than of the two-stranded one. The possibility of drastic changes in the structure of biopolymers with small pH changes in neutral region we have found for the poly-C--GTP system as an example may play an essential role in matrix synthesis and other intracellular processes.", "contents": "[Reaction between polycytidylic acid and guanosine-5'-triphosphate at neural pH]. The effect of changing the solution acidity in the interval of pH 7--8 on complex formation between polycytidilyc acid (polyC) and guanosine-5'-triphosphate (GTP) has been studied by the equilibrium dialysis and hydrogen ion titration methods. It is shown that in 1 M NaCl at 3 degrees C the complex stoichiometry undergoes changes in a narrow pH interval being equal to 2 poly C: 1 GTP at pH 7,0--7,3 and to 1 poly C:1 GTP at pH 7,6--8,0. In the presence of GTP the apparent pK of poly C protonation increases by 1,4 PK units and becomes equal to 7,1 in 1 M NaCl at 3 degrees C. Thus, the protonated poly-C takes part in the three-stranded poly-C--GTP complex formation. According to Hill's model of cooperative linear adsorption it is shown that the cooperativity of the three-stranded complex formation is greater than of the two-stranded one. The possibility of drastic changes in the structure of biopolymers with small pH changes in neutral region we have found for the poly-C--GTP system as an example may play an essential role in matrix synthesis and other intracellular processes."}
{"id": "PMID:25675", "title": "Nonenzymatic hydrolysis reactions of adenosine 5'-triphosphate and its related compounds. III: Catalytic aspects of some cobalt(III) complexes in ATP-hydrolysis.", "content": "Trichlorodiethylenetriaminecobalt (III), [CoCl3dien], which is provided with three good leaving ligands and, hence, capable of binding ATP in a characteristic mode, accelerated effectively and specifically hydrolysis of ATP to ADP and Pi. A kinetic study of the reaction indicated that the rate of hydrolysis was first order with respect to the concentration of ATP in the presence of an excess of [CoCl3dien]. The rate constant was calculated to be 1.05 X 10(-2) min-1 at pH 4.0 (50 degrees C), corresponding to a catalysis of the hydrolysis of ATP by a factor of 150. The complex possessing one good leaving ligand, chlorotetraethylenepentaminecobalt(III), and that having two of them in trans-position, dichlorobis(dimethylglyoximato)cobalt(III) only slightly enhanced the hydrolysis of ATP. Dichloro-cis-alpha- and dichloro-cis-beta-triethylenetetraminecobalt(III) complexes, which have two good leaving ligands and allow chelation of ATP in their coordination sphere, exhibited fairly good activities, although the hydrolysis reactions of ATP occurred in two modes as ATP leads to ADP + Pi and ATP leads to AMP + PPi. The mechanism of ATP-hydrolysis reaction with [CoCl3dien] was also discussed on the basis of the kinetic data.", "contents": "Nonenzymatic hydrolysis reactions of adenosine 5'-triphosphate and its related compounds. III: Catalytic aspects of some cobalt(III) complexes in ATP-hydrolysis. Trichlorodiethylenetriaminecobalt (III), [CoCl3dien], which is provided with three good leaving ligands and, hence, capable of binding ATP in a characteristic mode, accelerated effectively and specifically hydrolysis of ATP to ADP and Pi. A kinetic study of the reaction indicated that the rate of hydrolysis was first order with respect to the concentration of ATP in the presence of an excess of [CoCl3dien]. The rate constant was calculated to be 1.05 X 10(-2) min-1 at pH 4.0 (50 degrees C), corresponding to a catalysis of the hydrolysis of ATP by a factor of 150. The complex possessing one good leaving ligand, chlorotetraethylenepentaminecobalt(III), and that having two of them in trans-position, dichlorobis(dimethylglyoximato)cobalt(III) only slightly enhanced the hydrolysis of ATP. Dichloro-cis-alpha- and dichloro-cis-beta-triethylenetetraminecobalt(III) complexes, which have two good leaving ligands and allow chelation of ATP in their coordination sphere, exhibited fairly good activities, although the hydrolysis reactions of ATP occurred in two modes as ATP leads to ADP + Pi and ATP leads to AMP + PPi. The mechanism of ATP-hydrolysis reaction with [CoCl3dien] was also discussed on the basis of the kinetic data."}
{"id": "PMID:25672", "title": "[Coupled transport of K+, Cl-, H+ and OH- ions in a liposome suspension].", "content": "By means of the system of ion-selective electrodes the coupling transport of K+, H+ and Cl- ions in liposome suspension was studied. Nigericin and tributyl tin (TBT) were used as inductors of cation and anion exchange. Effect of pH gradient created on the membrane on ionic transport was studied. The latter was shown to control the antiport exchange of both, cations and anions. At the joint effect of nigericin and TBT the yield of K+ and Cl- ions from liposomes independent of the pH gradient was observed.", "contents": "[Coupled transport of K+, Cl-, H+ and OH- ions in a liposome suspension]. By means of the system of ion-selective electrodes the coupling transport of K+, H+ and Cl- ions in liposome suspension was studied. Nigericin and tributyl tin (TBT) were used as inductors of cation and anion exchange. Effect of pH gradient created on the membrane on ionic transport was studied. The latter was shown to control the antiport exchange of both, cations and anions. At the joint effect of nigericin and TBT the yield of K+ and Cl- ions from liposomes independent of the pH gradient was observed."}
{"id": "PMID:25676", "title": "Stacking interactions between aromatic amino acids and adenine ring of ATP in zinc mediated ternary complexes.", "content": "Spectrophotometric studies have provided evidence for zinc-mediated ternary complexes between ATP and aromatic amino acids. The hypochromicity observed in the 260 nm band of ATP increased in the order phenylalanine less than tyrosine less than tryptophan. Adding alanine did not produce any change of the ATP spectrum. The association constant was four fold higher for the ATP-Zinc-Tryptophan complex than for that of the ATP-Zinc-Alanine. The increased stability of the former complex was ascribed to the stacking interaction between indole and adenine rings. The maximum concentration of the ATP-Zinc-Tryptophan complex occurred at about pH 8.0. For these ternary complexes several possible stacked structures involving or not involving N(7) of adenine are discussed.", "contents": "Stacking interactions between aromatic amino acids and adenine ring of ATP in zinc mediated ternary complexes. Spectrophotometric studies have provided evidence for zinc-mediated ternary complexes between ATP and aromatic amino acids. The hypochromicity observed in the 260 nm band of ATP increased in the order phenylalanine less than tyrosine less than tryptophan. Adding alanine did not produce any change of the ATP spectrum. The association constant was four fold higher for the ATP-Zinc-Tryptophan complex than for that of the ATP-Zinc-Alanine. The increased stability of the former complex was ascribed to the stacking interaction between indole and adenine rings. The maximum concentration of the ATP-Zinc-Tryptophan complex occurred at about pH 8.0. For these ternary complexes several possible stacked structures involving or not involving N(7) of adenine are discussed."}
{"id": "PMID:25673", "title": "[Neuron membrane depolarization under the influence of cyclic-3',5'-adenosine monophosphate and its possible role in the neuronal molecular computer (MC)].", "content": "The separate fourth intracellular microelectrode was used for controlling the conditions of cyclic nucleotide injection in neurons of Helix pomatia. Ionoforetic increase in intracellular cyclic AMP concentration elicits membrane depolarization in many neurons. Phosphodiesterase inhibitors 3-isobutyl-1-methylxantine and SQ-20009 prolong this depolarization and raise its level. In cell F-1 of helix brain sometimes cAMP induces weak hyperpolarization, but this response turns to usual depolarization after 3-isobutyl-1-methylxantine application. It is suggested that cell molecular computer has an analog input, where diffusion of cAMP, cGMP and Ca++ being a modelling process. Adenylate cyclase and guanylate cyclase and ionic channels of membrane are regulated sources. Phosphodiesterases with Ca2+-binding activator proteins are molecular out flowers and protein kinases--detectors that transform the data about the concentrations of cAMP and cGMP into codes for MCC. Protein kinases control over the activity of proteins directly. The depolarization effect on neuron membrane seems to be associated with protein kinase activation or with direct action of cAMP on phospholipase.", "contents": "[Neuron membrane depolarization under the influence of cyclic-3',5'-adenosine monophosphate and its possible role in the neuronal molecular computer (MC)]. The separate fourth intracellular microelectrode was used for controlling the conditions of cyclic nucleotide injection in neurons of Helix pomatia. Ionoforetic increase in intracellular cyclic AMP concentration elicits membrane depolarization in many neurons. Phosphodiesterase inhibitors 3-isobutyl-1-methylxantine and SQ-20009 prolong this depolarization and raise its level. In cell F-1 of helix brain sometimes cAMP induces weak hyperpolarization, but this response turns to usual depolarization after 3-isobutyl-1-methylxantine application. It is suggested that cell molecular computer has an analog input, where diffusion of cAMP, cGMP and Ca++ being a modelling process. Adenylate cyclase and guanylate cyclase and ionic channels of membrane are regulated sources. Phosphodiesterases with Ca2+-binding activator proteins are molecular out flowers and protein kinases--detectors that transform the data about the concentrations of cAMP and cGMP into codes for MCC. Protein kinases control over the activity of proteins directly. The depolarization effect on neuron membrane seems to be associated with protein kinase activation or with direct action of cAMP on phospholipase."}
{"id": "PMID:25678", "title": "[Activity of gamma-glutamyl transferase of sheep cerebral cortex with respect to amino acids and glutathione].", "content": "gamma-glutamyl Transferase fron Sheep brain cortex capillaries was studied from the point of view of transport of aminoacids across blood brain barrier. Excess substrate inhibition was competitive and observed both with donor (glutathione) and various acceptors (methionine, alanine, tryptophan) but not with arginine. Excess glutathione inhibition of transfer reaction is concomitant with an increase of total reaction (transfer + hydrolysis + autotranspeptidation). With regard to aminoacids, the greater the K'm the stronger the inhibition. This inhibition is the result of formation of a dead complex. Lineweaver-Burk plots 1/v versus 1/[acceptor] give straight lines meeting at the same point, whereas 1/v verus 1/[donor] plots are roughly parallel for high aminoacid concentrations and become secant for the low ones. Replots of slopes vs. 1/[acceptor] are not linear: the lower the aminoacid affinity the more pronounced the slope replot curvature. Thus kinetic patterns are consistent with a branched ping-pong mechanism including a ternary complex (Enzyme-acceptor-H2O) at high or low relative concentration, which balances the two branches. The estimated value of kinetic parameters does not support the hypothesis of major implication of the enzyme in brain uptake of aminoacids.", "contents": "[Activity of gamma-glutamyl transferase of sheep cerebral cortex with respect to amino acids and glutathione]. gamma-glutamyl Transferase fron Sheep brain cortex capillaries was studied from the point of view of transport of aminoacids across blood brain barrier. Excess substrate inhibition was competitive and observed both with donor (glutathione) and various acceptors (methionine, alanine, tryptophan) but not with arginine. Excess glutathione inhibition of transfer reaction is concomitant with an increase of total reaction (transfer + hydrolysis + autotranspeptidation). With regard to aminoacids, the greater the K'm the stronger the inhibition. This inhibition is the result of formation of a dead complex. Lineweaver-Burk plots 1/v versus 1/[acceptor] give straight lines meeting at the same point, whereas 1/v verus 1/[donor] plots are roughly parallel for high aminoacid concentrations and become secant for the low ones. Replots of slopes vs. 1/[acceptor] are not linear: the lower the aminoacid affinity the more pronounced the slope replot curvature. Thus kinetic patterns are consistent with a branched ping-pong mechanism including a ternary complex (Enzyme-acceptor-H2O) at high or low relative concentration, which balances the two branches. The estimated value of kinetic parameters does not support the hypothesis of major implication of the enzyme in brain uptake of aminoacids."}
{"id": "PMID:25679", "title": "[Glutamate dehydrogenases of unicellular green algae: effects of nitrate and ammonium in vivo].", "content": "The constitution and control by the inorganic nitrogen source of glutamate dehydrogenases of some unicellular green algae have been studied. The Ankistrodesmus braunii and Scenedesmus obliquus cells contain two different glutamate dehydrogenases, one of which is NADP-specific, the other is active with both NAD and NADP. Their synthesis does not depend on the nitrogen source. The activity of NADP-specific glutamate dehydrogenase increases sharply during nitrogen starvation. In Chlorella pyrenoidosa 82 and Ch. ellipsoidea only one constitutive double specific glutamate dehydrogenase is observed. Its activity does not change depending on the nitrogen nutrition conditions. In the cells of the thermophylic Chlorella strain Chlorella sp. K. ammomium induces a de novo synthesis of NADP-specific glutamate dehydrogenase in addition to the constitutive double specific glutamate dehydrogenase. Thus, the algae tested contain constitutive double specific glutamate dehydrogenase. The NADP-specific enzyme is absent in two Chlorella strains, is constitutive in A. braunii and S. obliquus, and is ammonium-inducible in three thermophylic Chlorella strains.", "contents": "[Glutamate dehydrogenases of unicellular green algae: effects of nitrate and ammonium in vivo]. The constitution and control by the inorganic nitrogen source of glutamate dehydrogenases of some unicellular green algae have been studied. The Ankistrodesmus braunii and Scenedesmus obliquus cells contain two different glutamate dehydrogenases, one of which is NADP-specific, the other is active with both NAD and NADP. Their synthesis does not depend on the nitrogen source. The activity of NADP-specific glutamate dehydrogenase increases sharply during nitrogen starvation. In Chlorella pyrenoidosa 82 and Ch. ellipsoidea only one constitutive double specific glutamate dehydrogenase is observed. Its activity does not change depending on the nitrogen nutrition conditions. In the cells of the thermophylic Chlorella strain Chlorella sp. K. ammomium induces a de novo synthesis of NADP-specific glutamate dehydrogenase in addition to the constitutive double specific glutamate dehydrogenase. Thus, the algae tested contain constitutive double specific glutamate dehydrogenase. The NADP-specific enzyme is absent in two Chlorella strains, is constitutive in A. braunii and S. obliquus, and is ammonium-inducible in three thermophylic Chlorella strains."}
{"id": "PMID:25680", "title": "[Role of pyruvate kinase in non-specific changes of carbon photosynthetic metabolism, caused by the photophosphorylation inhibition].", "content": "The decrease in the level of NADP reduction in chloroplasts under injections of cofactors of pseudocyclic FMN photophosphorylation (vitamin K3 and methylviologen) into pea, tomato and cucumber leaves resulted in the decrease of 14CO2 autotrophic accumulation rate and in the change of distribution of assimilated carbon among the assimilation products. The inhibition of synthesis of labelled sugars and the increase of the content of 3-phosphoglyceric and glyceric acids in the labelled low molecular fraction were observed in all the experiments. Similar changes in the distribution of synthesized in Kalvin cycle labelled products, associated with the inhibition of its reduction unit, were observed under the effect of photophosphorylation uncoupling agents. However, the decrease of ATP/NADP ratio in chloroplasts resulted in the simultaneous increase of fixed 14CO2 incorporation into alanine. The role of pyruvate kinase in \"alanine\" effect, characteristic of non-specific changes of carbon photosynthetic metabolism, is discussed on the basis of the authors' previous data on the effect of phosphorylation on glycolysis reactions and on the basis of results of ADP introduction into leaf cuts.", "contents": "[Role of pyruvate kinase in non-specific changes of carbon photosynthetic metabolism, caused by the photophosphorylation inhibition]. The decrease in the level of NADP reduction in chloroplasts under injections of cofactors of pseudocyclic FMN photophosphorylation (vitamin K3 and methylviologen) into pea, tomato and cucumber leaves resulted in the decrease of 14CO2 autotrophic accumulation rate and in the change of distribution of assimilated carbon among the assimilation products. The inhibition of synthesis of labelled sugars and the increase of the content of 3-phosphoglyceric and glyceric acids in the labelled low molecular fraction were observed in all the experiments. Similar changes in the distribution of synthesized in Kalvin cycle labelled products, associated with the inhibition of its reduction unit, were observed under the effect of photophosphorylation uncoupling agents. However, the decrease of ATP/NADP ratio in chloroplasts resulted in the simultaneous increase of fixed 14CO2 incorporation into alanine. The role of pyruvate kinase in \"alanine\" effect, characteristic of non-specific changes of carbon photosynthetic metabolism, is discussed on the basis of the authors' previous data on the effect of phosphorylation on glycolysis reactions and on the basis of results of ADP introduction into leaf cuts."}
{"id": "PMID:25681", "title": "[Accessibility of sulfhydryl groups to 5,5'-dithiobis-2-nitrobenzoic acid and acid-base properties of bovine and walleye pollock rhodopsin preparations].", "content": "Both the number of exposed SH-groups and the rate of reaction with 5,5'dithiobis-2-nitrobenzoic acid (DTNB) in walleye pollock and bovine rhodopsin depend on a degree of native structure of the preparation to be investigated. The preparations studied can be arranged in the order of increase of these parameters as follows: ROS less than rhodopsin extracted by digitonin less than triton X-100 less than cetyltrimethylammonium bromide (CTAB) less than sodium dodecylsulphate (SDS). After illumination of ROS and digitonin, triton X-100 and CTAB-solubilized rhodopsin, and increase was observed in the number of modified SH-groups. Dark and bleached samples of walleye pollock rhodopsin exhibited a faster rate reaction and a more number of modified SH-groups as compared to bovine preparation. The differences between bovine and walleye pollock preparation disappeared after complete opsin unfolding as a result ROS solubilization in SDS. Six SH-groups per molecule of rhodopsin were modified in both preparation under these conditions. No differences in the number of cysteine residues (10--11), disulfide groups (2), acid (35--40) and base (25--30) titratable groups per rhodopsin molecule were found between bovine and walleye pollock ROS membranes. The isoelectric point of both rhodopsin preparations was within the pH range 5.2--5.6. After proteolysis of ROS with papain, a fragment with molecular weight 24500 +/- 1000 was detected, which contained the same number of SH-groups and cysteine residues as in the case of intact rhodopsin. The results obtained suggest that, in spite of a similar primary structure, the walleye pollock visual pigment has more \"loose\" and \"fluid\" space packing in the ROS membrane than the bovine pigment.", "contents": "[Accessibility of sulfhydryl groups to 5,5'-dithiobis-2-nitrobenzoic acid and acid-base properties of bovine and walleye pollock rhodopsin preparations]. Both the number of exposed SH-groups and the rate of reaction with 5,5'dithiobis-2-nitrobenzoic acid (DTNB) in walleye pollock and bovine rhodopsin depend on a degree of native structure of the preparation to be investigated. The preparations studied can be arranged in the order of increase of these parameters as follows: ROS less than rhodopsin extracted by digitonin less than triton X-100 less than cetyltrimethylammonium bromide (CTAB) less than sodium dodecylsulphate (SDS). After illumination of ROS and digitonin, triton X-100 and CTAB-solubilized rhodopsin, and increase was observed in the number of modified SH-groups. Dark and bleached samples of walleye pollock rhodopsin exhibited a faster rate reaction and a more number of modified SH-groups as compared to bovine preparation. The differences between bovine and walleye pollock preparation disappeared after complete opsin unfolding as a result ROS solubilization in SDS. Six SH-groups per molecule of rhodopsin were modified in both preparation under these conditions. No differences in the number of cysteine residues (10--11), disulfide groups (2), acid (35--40) and base (25--30) titratable groups per rhodopsin molecule were found between bovine and walleye pollock ROS membranes. The isoelectric point of both rhodopsin preparations was within the pH range 5.2--5.6. After proteolysis of ROS with papain, a fragment with molecular weight 24500 +/- 1000 was detected, which contained the same number of SH-groups and cysteine residues as in the case of intact rhodopsin. The results obtained suggest that, in spite of a similar primary structure, the walleye pollock visual pigment has more \"loose\" and \"fluid\" space packing in the ROS membrane than the bovine pigment."}
{"id": "PMID:25682", "title": "Magnetic circular dichroism studies of myoglobin, hemoglobin and peroxidase at room and low temperatures. Ferrous high spin derivatives.", "content": "The magnetic circular dichroism spectra (MCD) recorded for the visible and near-UV regions of high-spin ferrous derivatives of myoglobin, hemoglobin, hemoglobin dimers and isolated chains as well as of horseradish peroxidase at pH 6.8 and 11.4 have been compared at the room and liquid nitrogen temperatures. The MCD of the Q00- and QV-bands have been shown to be sensitive to structural differences in the heme environment of these hemoproteins. The room temperature visible MCD of native hemoglobin differs from that of myoglobin, hemoglobin dimers and isolated chains as well as from that of model pentacoordinated complex. The MCD of hemoglobin is characterized by the greater value of the MCD intensity ratio of derivative shape A-term in the Q00-band to the A-term in the QV-band. The evidneces are presented for the existence of two pH-dependent forms of ferroperoxidase, the neutral peroxidase shows the \"hemoglobin-like\" MCD, while the alkaline ferroperoxidase is characterized by the \"myoglobin-like\" MCD spectrum in the visible region. The differences in the MCD of deoxyhemoglobin and neutral ferroperoxidase as compared with other high-spin ferrous hemoproteins are considered to result from the constraints on heme group imposed by quaternary and/or tertiary protein structure. The differences between hemoporteins which are seen at the room temperature become more pronounced at liquid nitrogen temperature. Except the peak at approximately 580 nm in the MCD of deoxymyoglobin and reduced peroxidase at pH 11.4 the visible MCD does not show appreciable temperature dependent C-terms. The nature of the temperature dependent effect at approximately 580 nm is not clear. The Soret MCD of all hemoproteins studied are similar and are predominantly composed of the derivative-shaped C-terms as revealed by the increase of the MCD peaks approximately in accordance with Boltzmann distribution. The interpretation of temperature-dependent MCD observed for the Soret band has been made in terms of porphyrin to Fe-iron charge-transfer electronic transition which may be assigned as b( pi) leads to 3d. This charge-transfer band is strongly overlapped with usual B(pi --pi*) band resulting in diffuse Soret band. Adopting that only two normal vibrations are sinphase with charge-transfer transition the extracted C-terms of the Soret MCD have been fitted by theoretical dispersion curves.", "contents": "Magnetic circular dichroism studies of myoglobin, hemoglobin and peroxidase at room and low temperatures. Ferrous high spin derivatives. The magnetic circular dichroism spectra (MCD) recorded for the visible and near-UV regions of high-spin ferrous derivatives of myoglobin, hemoglobin, hemoglobin dimers and isolated chains as well as of horseradish peroxidase at pH 6.8 and 11.4 have been compared at the room and liquid nitrogen temperatures. The MCD of the Q00- and QV-bands have been shown to be sensitive to structural differences in the heme environment of these hemoproteins. The room temperature visible MCD of native hemoglobin differs from that of myoglobin, hemoglobin dimers and isolated chains as well as from that of model pentacoordinated complex. The MCD of hemoglobin is characterized by the greater value of the MCD intensity ratio of derivative shape A-term in the Q00-band to the A-term in the QV-band. The evidneces are presented for the existence of two pH-dependent forms of ferroperoxidase, the neutral peroxidase shows the \"hemoglobin-like\" MCD, while the alkaline ferroperoxidase is characterized by the \"myoglobin-like\" MCD spectrum in the visible region. The differences in the MCD of deoxyhemoglobin and neutral ferroperoxidase as compared with other high-spin ferrous hemoproteins are considered to result from the constraints on heme group imposed by quaternary and/or tertiary protein structure. The differences between hemoporteins which are seen at the room temperature become more pronounced at liquid nitrogen temperature. Except the peak at approximately 580 nm in the MCD of deoxymyoglobin and reduced peroxidase at pH 11.4 the visible MCD does not show appreciable temperature dependent C-terms. The nature of the temperature dependent effect at approximately 580 nm is not clear. The Soret MCD of all hemoproteins studied are similar and are predominantly composed of the derivative-shaped C-terms as revealed by the increase of the MCD peaks approximately in accordance with Boltzmann distribution. The interpretation of temperature-dependent MCD observed for the Soret band has been made in terms of porphyrin to Fe-iron charge-transfer electronic transition which may be assigned as b( pi) leads to 3d. This charge-transfer band is strongly overlapped with usual B(pi --pi*) band resulting in diffuse Soret band. Adopting that only two normal vibrations are sinphase with charge-transfer transition the extracted C-terms of the Soret MCD have been fitted by theoretical dispersion curves."}
{"id": "PMID:25683", "title": "Immobilization of Streptomyces flavochromogenes pullulanase on tannic acid and TEAE--cellulose.", "content": "Pullulanase was immobilized successfully by simple, inexpensive methods that may be useful for industrial application of this enzyme. A tannin--pullulanase(TP) complex was obtained by addition of tannic acid to the culture filtrate of thermophilic Streptomyces flavochromogenes. TP could be bound to TEAE--cellulose (TTCP). Immobilization in this manner took place with quantitative retention of activity. The immobilized enzymes were stable for more than six months. The optimum temperatures of the native enzyme and TP were both 50 degrees C; that of TTCP was 45 degrees C. In the presence of 5mM Ca2+, the activity of TTCP was increased approximately twofold and the optimum temperature was raised to 50--60 degrees C. Pullulanase was not significantly eluted from TP or TTCP by NaCl solution (0.1--0.5M).", "contents": "Immobilization of Streptomyces flavochromogenes pullulanase on tannic acid and TEAE--cellulose. Pullulanase was immobilized successfully by simple, inexpensive methods that may be useful for industrial application of this enzyme. A tannin--pullulanase(TP) complex was obtained by addition of tannic acid to the culture filtrate of thermophilic Streptomyces flavochromogenes. TP could be bound to TEAE--cellulose (TTCP). Immobilization in this manner took place with quantitative retention of activity. The immobilized enzymes were stable for more than six months. The optimum temperatures of the native enzyme and TP were both 50 degrees C; that of TTCP was 45 degrees C. In the presence of 5mM Ca2+, the activity of TTCP was increased approximately twofold and the optimum temperature was raised to 50--60 degrees C. Pullulanase was not significantly eluted from TP or TTCP by NaCl solution (0.1--0.5M)."}
{"id": "PMID:25686", "title": "Purinergic innervation of the guinea-pig urinary bladder.", "content": "1 A number of criteria for considering adenosine 5'-triphosphate (ATP) as a neurotransmitter in the guinea-pig urinary bladder have been examined. In addition, the effect of tachyphylaxis to ATP on the response to non-adrenergic, non-cholinergic nerve stimulation has been re-examined.2 Quinacrine fluorescence histochemistry revealed a population of nerve fibres, ganglion cells, and nerve bundles in the bladder which were not seen in either the iris or vas deferens, where adrenergic and cholinergic nerves predominate. The distribution and morphology of the quinacrine-positive nerves in the bladder were different from those observed with catecholamine fluorescence and cholinesterase histochemistry, and were unaffected by chemical sympathectomy.3 Release of ATP from the bladder during stimulation of intramural excitatory nerves, in the presence of atropine and guanethidine increased to 3-12 times prestimulation levels. Tetrodotoxin abolished both the contractile response and the increase in ATP release resulting from intramural nerve stimulation. There was no increase in ATP release during contraction resulting from direct muscle stimulation following nerve paralysis with tetrodotoxin.4 Sympathectomy with 6-hydroxydopamine did not affect release of ATP in response to intramural nerve stimulation.5 Release of ATP was dependent on the concentration of calcium ion in the medium.6 Contractions in response to non-adrenergic, non-cholinergic intramural nerve stimulation were closely mimicked by ATP, but not by acetylcholine or histamine.7 Adenosine and dipyridamole reduced the contractions to both ATP and non-cholinergic nerve stimulation.8 2-2'-Pyridylisatogen was not a specific blocker of either ATP or intramural nerve stimulation in the guinea-pig bladder. 2-Substituted imidazolines initiated spontaneous activity making it impossible to assess any blocking action that they may have had.9 Prostaglandins (E(1), E(2) and F(2alpha)) gave weak, slow contractions and an increase in spontaneous activity. Both the response to ATP and non-adrenergic, non-cholinergic nerve stimulation were greatly potentiated in the presence of prostaglandins.10 In the presence of indomethacin the response to non-adrenergic, non-cholinergic nerve stimulation was virtually abolished following desensitization to ATP.", "contents": "Purinergic innervation of the guinea-pig urinary bladder. 1 A number of criteria for considering adenosine 5'-triphosphate (ATP) as a neurotransmitter in the guinea-pig urinary bladder have been examined. In addition, the effect of tachyphylaxis to ATP on the response to non-adrenergic, non-cholinergic nerve stimulation has been re-examined.2 Quinacrine fluorescence histochemistry revealed a population of nerve fibres, ganglion cells, and nerve bundles in the bladder which were not seen in either the iris or vas deferens, where adrenergic and cholinergic nerves predominate. The distribution and morphology of the quinacrine-positive nerves in the bladder were different from those observed with catecholamine fluorescence and cholinesterase histochemistry, and were unaffected by chemical sympathectomy.3 Release of ATP from the bladder during stimulation of intramural excitatory nerves, in the presence of atropine and guanethidine increased to 3-12 times prestimulation levels. Tetrodotoxin abolished both the contractile response and the increase in ATP release resulting from intramural nerve stimulation. There was no increase in ATP release during contraction resulting from direct muscle stimulation following nerve paralysis with tetrodotoxin.4 Sympathectomy with 6-hydroxydopamine did not affect release of ATP in response to intramural nerve stimulation.5 Release of ATP was dependent on the concentration of calcium ion in the medium.6 Contractions in response to non-adrenergic, non-cholinergic intramural nerve stimulation were closely mimicked by ATP, but not by acetylcholine or histamine.7 Adenosine and dipyridamole reduced the contractions to both ATP and non-cholinergic nerve stimulation.8 2-2'-Pyridylisatogen was not a specific blocker of either ATP or intramural nerve stimulation in the guinea-pig bladder. 2-Substituted imidazolines initiated spontaneous activity making it impossible to assess any blocking action that they may have had.9 Prostaglandins (E(1), E(2) and F(2alpha)) gave weak, slow contractions and an increase in spontaneous activity. Both the response to ATP and non-adrenergic, non-cholinergic nerve stimulation were greatly potentiated in the presence of prostaglandins.10 In the presence of indomethacin the response to non-adrenergic, non-cholinergic nerve stimulation was virtually abolished following desensitization to ATP."}
{"id": "PMID:25687", "title": "Inhibition of [3H]-dihydroalprenolol binding to rat cardiac membranes of various beta-blocking agents.", "content": "Binding of [3-H]-dihydroalprenolol ([3-H]-DHA) to rat cardiac membranes was rapid and reversible (k1 = 0.633-0.701 x 10(6) M(-1) S(-1) And k(-1) = 0.0017-0.0043 s(-1). 2 [3-H]-DHA bound to a single class of binding sites with an equilibrium dissociation constant (Kd25degreesc) of 5.7+/-1.1 x 10(-9) M. 3 This binding was specific and the order of potency of adrenoceptor agonists in competing for the binding sites was (-)-isoproterenol greater than (+/-)-isoproternol greater than (+)-isoproterenol greater than (-)-adrenaline greater than (-)-noradrenaline. This was in agreement with the beta1 nature of the cardiac beta-receptors. 4 Cardioselective beta-blockers (i.e. metoprolol, acebutolol and practolol) were shown to have lower binding site affinities, when compared to other blockers. This may be related to steric hindrance by the side-chain at the aromatic end of these molecules.", "contents": "Inhibition of [3H]-dihydroalprenolol binding to rat cardiac membranes of various beta-blocking agents. Binding of [3-H]-dihydroalprenolol ([3-H]-DHA) to rat cardiac membranes was rapid and reversible (k1 = 0.633-0.701 x 10(6) M(-1) S(-1) And k(-1) = 0.0017-0.0043 s(-1). 2 [3-H]-DHA bound to a single class of binding sites with an equilibrium dissociation constant (Kd25degreesc) of 5.7+/-1.1 x 10(-9) M. 3 This binding was specific and the order of potency of adrenoceptor agonists in competing for the binding sites was (-)-isoproterenol greater than (+/-)-isoproternol greater than (+)-isoproterenol greater than (-)-adrenaline greater than (-)-noradrenaline. This was in agreement with the beta1 nature of the cardiac beta-receptors. 4 Cardioselective beta-blockers (i.e. metoprolol, acebutolol and practolol) were shown to have lower binding site affinities, when compared to other blockers. This may be related to steric hindrance by the side-chain at the aromatic end of these molecules."}
{"id": "PMID:25692", "title": "Glycine high affinity uptake and strychnine binding associated with glycine receptors in the frog central nervous system.", "content": "Accumulation of [3H]glycine into synaptosomal fractions occurs by high affinity systems in cerebral cortex, optic tectum, brain stem and spinal cord of the frog. Specific [3H]strychnine binding which appears associated with postsynaptic glycine receptors is also demonstrable in these regions. By contrast, only very low levels of strychnine binding and high affinity glycine uptake occur in higher centers of the rat central nervous system. The relative potencies of small neutral amino acids in competing for [3H]strychnine binding are similar in frog brain and spinal cord. No evidence for a high affinity accumulation of [3H]taurine by synaptosomal fractions of frog spinal cord can be demonstrated. These observations favor glycine rather than taurine as an inhibitory transmitter in frog spinal cord. Moreover, these findings suggest that glycine may have a synaptic role in higher brain centers in the frog.", "contents": "Glycine high affinity uptake and strychnine binding associated with glycine receptors in the frog central nervous system. Accumulation of [3H]glycine into synaptosomal fractions occurs by high affinity systems in cerebral cortex, optic tectum, brain stem and spinal cord of the frog. Specific [3H]strychnine binding which appears associated with postsynaptic glycine receptors is also demonstrable in these regions. By contrast, only very low levels of strychnine binding and high affinity glycine uptake occur in higher centers of the rat central nervous system. The relative potencies of small neutral amino acids in competing for [3H]strychnine binding are similar in frog brain and spinal cord. No evidence for a high affinity accumulation of [3H]taurine by synaptosomal fractions of frog spinal cord can be demonstrated. These observations favor glycine rather than taurine as an inhibitory transmitter in frog spinal cord. Moreover, these findings suggest that glycine may have a synaptic role in higher brain centers in the frog."}
{"id": "PMID:25696", "title": "The effect of castration, thyroidectomy and haloperidol upon the turnover rates of dopamine and norepinephrine and the kinetic properties of tyrosine hydroxylase in discrete hypothalamic nuclei of the male rat.", "content": "Adult male rats were either castrated, thyroidectomized, or treated with haloperidol and the rates of turnover of dopamine (DA) and norepinephrine (NE) in the median eminence (ME), the arcuate and dorsomedial nuclei of the hypothalamus were estimated from the rate of decay of DA and NE concentrations as determined by radioenzymatic assay following blockade of catecholamine synthesis by alpha-methyl-p-tyrosine. The ME of animals similarly prepared was also examined for changes in the total activity and kinetic properties of tyrosine hydroxylase (TH). Four days following the administration of haloperidol (400 microgram/kg) or 10 days after castration, there was a significant increase in the rate of turnover of DA but not NE in the ME accompanied by an increase in the Vmax but not Km for the substrate or cofactor of TH. Furthermore, the administration of haloperidol to hypophysectomized rats also significantly increased the TH activity in the ME, indicating that such changes may occur independently of any changes in serum prolactin levels. Ten days after thyroidectomy, or three weeks after treatment with prophylthiouracil, there was a significant increase in the turnover rate of DA in both the ME and dorsomedial nucleus but not in the arcuate nucleus. No changes in the turnover rates of NE in any of the three areas were observed following thyroidectomy. In the ME, the increase in turnover of DA was accompanied by an increase in the total TH activity (Vmax) as welll as a decrease in Km for tetrahydrobiopterin but not tyrosine. From these results 4 conclusions were drawn: (1) following halperidol, castration, and thyroidectomy there are increases in the activity of dopaminergic terminals within the ME; (2) castration, haloperidol and thyroidectomy may influence the activity of dopaminergic terminals within the ME by different mechanisms; (3) changes in tyrosine hydroxylase and turnover of catecholamines within the ME may occur independently of changes in prolactin levels; and (4) local recurrent afferent circuits may exist in the arcuate nucleus region of the hypothalamus.", "contents": "The effect of castration, thyroidectomy and haloperidol upon the turnover rates of dopamine and norepinephrine and the kinetic properties of tyrosine hydroxylase in discrete hypothalamic nuclei of the male rat. Adult male rats were either castrated, thyroidectomized, or treated with haloperidol and the rates of turnover of dopamine (DA) and norepinephrine (NE) in the median eminence (ME), the arcuate and dorsomedial nuclei of the hypothalamus were estimated from the rate of decay of DA and NE concentrations as determined by radioenzymatic assay following blockade of catecholamine synthesis by alpha-methyl-p-tyrosine. The ME of animals similarly prepared was also examined for changes in the total activity and kinetic properties of tyrosine hydroxylase (TH). Four days following the administration of haloperidol (400 microgram/kg) or 10 days after castration, there was a significant increase in the rate of turnover of DA but not NE in the ME accompanied by an increase in the Vmax but not Km for the substrate or cofactor of TH. Furthermore, the administration of haloperidol to hypophysectomized rats also significantly increased the TH activity in the ME, indicating that such changes may occur independently of any changes in serum prolactin levels. Ten days after thyroidectomy, or three weeks after treatment with prophylthiouracil, there was a significant increase in the turnover rate of DA in both the ME and dorsomedial nucleus but not in the arcuate nucleus. No changes in the turnover rates of NE in any of the three areas were observed following thyroidectomy. In the ME, the increase in turnover of DA was accompanied by an increase in the total TH activity (Vmax) as welll as a decrease in Km for tetrahydrobiopterin but not tyrosine. From these results 4 conclusions were drawn: (1) following halperidol, castration, and thyroidectomy there are increases in the activity of dopaminergic terminals within the ME; (2) castration, haloperidol and thyroidectomy may influence the activity of dopaminergic terminals within the ME by different mechanisms; (3) changes in tyrosine hydroxylase and turnover of catecholamines within the ME may occur independently of changes in prolactin levels; and (4) local recurrent afferent circuits may exist in the arcuate nucleus region of the hypothalamus."}
{"id": "PMID:25697", "title": "Pharmacologic responses of cells of a neuroblastoma X glioma hybrid clone and modulation of synapses between hybrid cells and mouse myotubes.", "content": "Cells of the hybrid clone NG108-15 responded to 5-hydroxytryptamine (5-HT), dopamine or acetylcholine with graded depolarizations involving membrane conductance increases. Responses desensitized during continuous application of the neurotransmitters, and responses to 5-HT and dopamine cross-desensitized: a desensitizing application of one neurotransmitter also desensitized the hybrd cell to the other neurotransmitter. 5-HT and acetylcholine did not cross-desensitize. The hybrid cell 5-HT response was not attenuated by D-LSD, and was blocked by 10(-5) M morphine, although not via binding to naloxone-sensitive opiate receptors. 5-HT or the prostaglandin PGF2alpha caused the release of acetylcholine at the synapses of hybrid cells with mouse myotubes. Application of 5-HT or PGF2alpha also facilitated the synaptic release elicited by hybrid cell action potentials. Following treatment with the antimitotic agent cytosine arabinoside, co-cultures of hybrid cells and mouse myotubes exhibited plentiful synaptic connections only if maintained in medium containing 1 mM dibutyryl cAMP (dBcAMP). After X-irradiation, co-cultures were synaptically active even in the absence of dBcAMP. Thus, methods have been found to regulate both the short-term and long-term synaptic activity of NG108-15 hybrid cells.", "contents": "Pharmacologic responses of cells of a neuroblastoma X glioma hybrid clone and modulation of synapses between hybrid cells and mouse myotubes. Cells of the hybrid clone NG108-15 responded to 5-hydroxytryptamine (5-HT), dopamine or acetylcholine with graded depolarizations involving membrane conductance increases. Responses desensitized during continuous application of the neurotransmitters, and responses to 5-HT and dopamine cross-desensitized: a desensitizing application of one neurotransmitter also desensitized the hybrd cell to the other neurotransmitter. 5-HT and acetylcholine did not cross-desensitize. The hybrid cell 5-HT response was not attenuated by D-LSD, and was blocked by 10(-5) M morphine, although not via binding to naloxone-sensitive opiate receptors. 5-HT or the prostaglandin PGF2alpha caused the release of acetylcholine at the synapses of hybrid cells with mouse myotubes. Application of 5-HT or PGF2alpha also facilitated the synaptic release elicited by hybrid cell action potentials. Following treatment with the antimitotic agent cytosine arabinoside, co-cultures of hybrid cells and mouse myotubes exhibited plentiful synaptic connections only if maintained in medium containing 1 mM dibutyryl cAMP (dBcAMP). After X-irradiation, co-cultures were synaptically active even in the absence of dBcAMP. Thus, methods have been found to regulate both the short-term and long-term synaptic activity of NG108-15 hybrid cells."}
{"id": "PMID:25699", "title": "A thermodynamic analysis of the amorphous to crystalline calcium phosphate transformation.", "content": "A thermodynamic analysis of the precipitation of amorphous calcium phosphate (ACP) and its transformation to crystalline apatite had been made. A nearly constant ion product, over a wide variety of conditions, was obtained for a tricalcium phosphate (TCP)-like phase suggesting that the molecular unit which governs the solubility of ACP may be similar in composition to TCP. The introduction of 10% acid phosphate into the formula for the TCP ion product improves the fit of experimental data and results in an invariant ion product. The stability of ACP in solution was found to be dependent upon its thermodynamic instability with respect to an octacalcium phosphate (OCP)-like phase. The dependence of the induction period for the amorphous to crystalline transformation upon the pH and the Ca/P ratio of the solution is best explained by the assumption that an OCP-like phase is initially nucleated on the surfaces of the ACP particles. The events that occur in the immediate post-transition period suggest the hydrolysis of this OCP-like material to an apatitic phase.", "contents": "A thermodynamic analysis of the amorphous to crystalline calcium phosphate transformation. A thermodynamic analysis of the precipitation of amorphous calcium phosphate (ACP) and its transformation to crystalline apatite had been made. A nearly constant ion product, over a wide variety of conditions, was obtained for a tricalcium phosphate (TCP)-like phase suggesting that the molecular unit which governs the solubility of ACP may be similar in composition to TCP. The introduction of 10% acid phosphate into the formula for the TCP ion product improves the fit of experimental data and results in an invariant ion product. The stability of ACP in solution was found to be dependent upon its thermodynamic instability with respect to an octacalcium phosphate (OCP)-like phase. The dependence of the induction period for the amorphous to crystalline transformation upon the pH and the Ca/P ratio of the solution is best explained by the assumption that an OCP-like phase is initially nucleated on the surfaces of the ACP particles. The events that occur in the immediate post-transition period suggest the hydrolysis of this OCP-like material to an apatitic phase."}
{"id": "PMID:25701", "title": "Complement activating factor(s) of Trypanosoma lewisi: some physiochemical characteristics of the active components.", "content": "Of the complement activating factors present in Trypanosoma lewisi, the major component, a carbohydrate containing substance was further investigated. This component was found to have a lag time of complete activation of 2 CH50 units of bovine complement of approximately 15 minutes while 1% trypsin (a known activator of complement, used as a control system) was capable of instant consumption of a similar quantity of complement. In addition, the complement activating factor of trypanosomes was observed to be stable at 100 degrees C for 15 minutes and over a pH range of 3.0 to 11.0. Thin layer chromatography studies suggested that at least part of the active component contained lipid, perhaps indicating that it may be glycolipid in nature.", "contents": "Complement activating factor(s) of Trypanosoma lewisi: some physiochemical characteristics of the active components. Of the complement activating factors present in Trypanosoma lewisi, the major component, a carbohydrate containing substance was further investigated. This component was found to have a lag time of complete activation of 2 CH50 units of bovine complement of approximately 15 minutes while 1% trypsin (a known activator of complement, used as a control system) was capable of instant consumption of a similar quantity of complement. In addition, the complement activating factor of trypanosomes was observed to be stable at 100 degrees C for 15 minutes and over a pH range of 3.0 to 11.0. Thin layer chromatography studies suggested that at least part of the active component contained lipid, perhaps indicating that it may be glycolipid in nature."}
{"id": "PMID:25702", "title": "Blood flow in rabbit eyes after keratectomy and corneal transplantation.", "content": "We used radio-labelled microspheres to study the distribution of blood flow in different regions of rabbit eyes with inflamed corneas resulting from trauma or allograft reaction. The blood flow in the cornea, the anterior uvea and the regional lymph nodes draining it was increased, but total flow in the eye did not increase. More blood went to the anterior uvea at the expense of the rest of the eye. Blood flow at the limbus was higher in the inflamed corneas than in the controls.", "contents": "Blood flow in rabbit eyes after keratectomy and corneal transplantation. We used radio-labelled microspheres to study the distribution of blood flow in different regions of rabbit eyes with inflamed corneas resulting from trauma or allograft reaction. The blood flow in the cornea, the anterior uvea and the regional lymph nodes draining it was increased, but total flow in the eye did not increase. More blood went to the anterior uvea at the expense of the rest of the eye. Blood flow at the limbus was higher in the inflamed corneas than in the controls."}
{"id": "PMID:25703", "title": "Phosphate metabolism in blue-green bacteria. V. Factors affecting phosphate uptake in Plectonema boryanum.", "content": "Plectonema boryanum requires approximately 5 days of exposure to a culture medium lacking phosphorus to induce the \"polyphosphate overplus\" phenomenon. At pH9, phosphate uptake is greatest both from normal culture medium and from dilute salt solutions. Phosphate uptake from dilute salt solutions was greatest when Na+ or K+ are combined with Ca2+ or Ca2+ and Mg2+. Cells starved of phosphorus in the presence of a high concentration of K+ or Ca2+ in the medium, and then allowed to take up phosphorus under the same conditions, assimilate more phosphorus than with other major ions.", "contents": "Phosphate metabolism in blue-green bacteria. V. Factors affecting phosphate uptake in Plectonema boryanum. Plectonema boryanum requires approximately 5 days of exposure to a culture medium lacking phosphorus to induce the \"polyphosphate overplus\" phenomenon. At pH9, phosphate uptake is greatest both from normal culture medium and from dilute salt solutions. Phosphate uptake from dilute salt solutions was greatest when Na+ or K+ are combined with Ca2+ or Ca2+ and Mg2+. Cells starved of phosphorus in the presence of a high concentration of K+ or Ca2+ in the medium, and then allowed to take up phosphorus under the same conditions, assimilate more phosphorus than with other major ions."}
{"id": "PMID:25704", "title": "Effect of osmotic potential, pH, and temperature on the growth of a helical, motile mycoplasma causing corn stunt disease.", "content": "Growth characteristics of corn stunt spiroplasma, a helical, motile mycoplasma, were studied over a range of osmolality, pH, and temperature in a simple medium containing 20% (v/v) agamma horse serum, 1.5% (w/v) PPLO broth, and various concentrations of sucrose. The spiroplasma was able to grow in a wide spectrum of osmolalities from 360 to 1120 mosm. Optimal growth was observed in media that contained 0.25-0.35 M sucrose. The organism became longer and thinner in media adjusted to 0.65 M sucrose or more. The spiroplasma lost helicity and motility immediately after transfer to media at pH 5.4 or lower. Optimal pH for growth was 7.2. No growth was observed at pH lower than 5.4 or higher than 8.0. Optimal temperature for growth was 32 degrees C. Very little or no growth was observed at temperatures lower than 15 degrees C or higher than 35 degrees C.", "contents": "Effect of osmotic potential, pH, and temperature on the growth of a helical, motile mycoplasma causing corn stunt disease. Growth characteristics of corn stunt spiroplasma, a helical, motile mycoplasma, were studied over a range of osmolality, pH, and temperature in a simple medium containing 20% (v/v) agamma horse serum, 1.5% (w/v) PPLO broth, and various concentrations of sucrose. The spiroplasma was able to grow in a wide spectrum of osmolalities from 360 to 1120 mosm. Optimal growth was observed in media that contained 0.25-0.35 M sucrose. The organism became longer and thinner in media adjusted to 0.65 M sucrose or more. The spiroplasma lost helicity and motility immediately after transfer to media at pH 5.4 or lower. Optimal pH for growth was 7.2. No growth was observed at pH lower than 5.4 or higher than 8.0. Optimal temperature for growth was 32 degrees C. Very little or no growth was observed at temperatures lower than 15 degrees C or higher than 35 degrees C."}
{"id": "PMID:25705", "title": "Brain metabolism and arterial acid-base balance following bilateral carotid occlusion in normotensive and experimental hypertensive rats.", "content": "The effects of bilateral common carotid artery occlusion on brain metabolism and arterial acid-base balance were studied in normotensive and experimental renovascular hypertensive rats. One hour after carotid occlusion in hypertensive rats, supratentorial lactate increased to 383% and lactate-pyruvate ratio to 280% of the controls, while adenosine triphosphate (ATP) decreased to 69%. These metabolic changes were thought to be due to cerebral ischemia. Arterial pCO2 was lowered and the pH was raised in the hypertensive animals due to cerebral ischemia induced hyperventilation. In the normotensive rats, carotid occlusion had minimal effects on cerebral metabolism and arterial acid-base balance. These results suggest that hypertensive rats are more susceptible to cerebral ischemia caused by carotid occlusion than normotensive rats. Increased cerebrovascular resistance in hypertension is discussed as a causal factor in cerebral ischemia.", "contents": "Brain metabolism and arterial acid-base balance following bilateral carotid occlusion in normotensive and experimental hypertensive rats. The effects of bilateral common carotid artery occlusion on brain metabolism and arterial acid-base balance were studied in normotensive and experimental renovascular hypertensive rats. One hour after carotid occlusion in hypertensive rats, supratentorial lactate increased to 383% and lactate-pyruvate ratio to 280% of the controls, while adenosine triphosphate (ATP) decreased to 69%. These metabolic changes were thought to be due to cerebral ischemia. Arterial pCO2 was lowered and the pH was raised in the hypertensive animals due to cerebral ischemia induced hyperventilation. In the normotensive rats, carotid occlusion had minimal effects on cerebral metabolism and arterial acid-base balance. These results suggest that hypertensive rats are more susceptible to cerebral ischemia caused by carotid occlusion than normotensive rats. Increased cerebrovascular resistance in hypertension is discussed as a causal factor in cerebral ischemia."}
{"id": "PMID:25706", "title": "Cardiac pharmacology and cardiomyopathy in Friedreich's ataxia.", "content": "Friedreich's ataxia is almost always associated with a cardiomyopathy. The cardiomyopathy and its attendant cardiopulmonary sequelae is the usual cause of death in this disease. The author reviews the known pharmacology of the heart, particularly as it applies to hypertrophic cardiomyopathy. The important role played by calcium and the possible role of taurine is stressed. Therapeutic possibilities are mentioned.", "contents": "Cardiac pharmacology and cardiomyopathy in Friedreich's ataxia. Friedreich's ataxia is almost always associated with a cardiomyopathy. The cardiomyopathy and its attendant cardiopulmonary sequelae is the usual cause of death in this disease. The author reviews the known pharmacology of the heart, particularly as it applies to hypertrophic cardiomyopathy. The important role played by calcium and the possible role of taurine is stressed. Therapeutic possibilities are mentioned."}
{"id": "PMID:25707", "title": "Treatment of arterial hypertension with tienilic acid, a new diuretic with uricosuric properties.", "content": "Tienilic acid--2,3-dichloro-4-(2-thienyl-carbonyl)phenoxyacetic acid--is a new diuretic with uricosuric properties. Nineteen patients with moderate arterial hypertension were treated for 5 consecutive weeks in a randomized fashion in a double-blind study with either tienilic acid or hydrochlorothiazide. Blood pressure was significantly reduced and to the same degree with both drugs. In 7 of the 11 patients receiving tienilic acid the daily dose was increased from 250 to 500 mg after 2 weeks, and in 2 of the 8 patients taking hydrochlorothiazide the daily dose was increased from 50 to 100 mg. Because of the potent uricosuric action of tienilic acid the mean serum urate concentration decreased from 6.3 to 3.3 mg/dL in the patients taking the drug. In contrast, the patients receiving hydrochlorothiazide the mean serum urate concentration increased from 6.1 to 7.8 mg/dL. Moderate hypokalemia of almost identical degree (mean serum potassium values 3.6 and 3.5 mmol/L) and mild metabolic alkalosis were observed in both groups. Tienilic acid had a marked hypocalciuric effect, which was of the same magnitude as the observed with hydrochlorothiazide. During the 5 weeks of treatment no significant change in renal or liver function was observed in either group. There were no hematologic complications and the drug was remarkably well tolerated. Tienilic acid, because of its unique character as a diuretic, hypouricemic and antihypertensive agent, should become the preferred drug for the treatment of arterial hypertension.", "contents": "Treatment of arterial hypertension with tienilic acid, a new diuretic with uricosuric properties. Tienilic acid--2,3-dichloro-4-(2-thienyl-carbonyl)phenoxyacetic acid--is a new diuretic with uricosuric properties. Nineteen patients with moderate arterial hypertension were treated for 5 consecutive weeks in a randomized fashion in a double-blind study with either tienilic acid or hydrochlorothiazide. Blood pressure was significantly reduced and to the same degree with both drugs. In 7 of the 11 patients receiving tienilic acid the daily dose was increased from 250 to 500 mg after 2 weeks, and in 2 of the 8 patients taking hydrochlorothiazide the daily dose was increased from 50 to 100 mg. Because of the potent uricosuric action of tienilic acid the mean serum urate concentration decreased from 6.3 to 3.3 mg/dL in the patients taking the drug. In contrast, the patients receiving hydrochlorothiazide the mean serum urate concentration increased from 6.1 to 7.8 mg/dL. Moderate hypokalemia of almost identical degree (mean serum potassium values 3.6 and 3.5 mmol/L) and mild metabolic alkalosis were observed in both groups. Tienilic acid had a marked hypocalciuric effect, which was of the same magnitude as the observed with hydrochlorothiazide. During the 5 weeks of treatment no significant change in renal or liver function was observed in either group. There were no hematologic complications and the drug was remarkably well tolerated. Tienilic acid, because of its unique character as a diuretic, hypouricemic and antihypertensive agent, should become the preferred drug for the treatment of arterial hypertension."}
{"id": "PMID:25708", "title": "Minor tranquillizers in somatic disorders.", "content": "Conclusive evidence of improved outcome due to adjunctive anxiolytic therapy in some somatic conditions is lacking. However, such therapy may facilitate patient management without being \"curative\". The resulting improved feeling of well-being may be of value in the management of gastrointestinal disorders, migraine and myocardial infarction. Negative effects may be observed in acute respiratory conditions, especially during acute exacerbations of chronic conditions, with the administration of benzodiazepines; hence they should be used with caution. The use of these agents in treating persons with hypertension seems to be of no value and may even be detrimental. Careful evaluation of each case is desirable, and treatment should be planned with its termination in mind.", "contents": "Minor tranquillizers in somatic disorders. Conclusive evidence of improved outcome due to adjunctive anxiolytic therapy in some somatic conditions is lacking. However, such therapy may facilitate patient management without being \"curative\". The resulting improved feeling of well-being may be of value in the management of gastrointestinal disorders, migraine and myocardial infarction. Negative effects may be observed in acute respiratory conditions, especially during acute exacerbations of chronic conditions, with the administration of benzodiazepines; hence they should be used with caution. The use of these agents in treating persons with hypertension seems to be of no value and may even be detrimental. Careful evaluation of each case is desirable, and treatment should be planned with its termination in mind."}
{"id": "PMID:25709", "title": "Hormonal regulation and the effects of glucose on tyrosine aminotransferase activity in adult rat hepatocytes cultured on floating collagen membranes.", "content": "Adult rat parenchymal hepatocytes can be maintained in primary culture on floating collagen membranes of prolonged periods of time. In this system the enzyme tyrosine aminotransferase is induced by glucagon, (10(-6) to 10(-8) M) hydrocortisone (10(-5) to 10(-8) M), and cyclic adenosine 3':5'-monophosphate (cAMP) (10(-4) to 10(-5) M). Epinephrine (10(-4) M) induces the enzyme only in the presence of hydrocortisone. Addition of actinomycin D inhibited the induction of tyrosine aminotransferase by hydrocortisone and cAMP. Maintenance of the cultured hepatocytes in the presence of glucose (3g/liter) results in partial suppression of the inducing effects of glucagon and cAMP. Cyclic quanosine 3':5'-monophosphate does not mimic the effects of glucose. These results demonstrate that the phenomenon of glucose repression of enzyme induction, demonstrated in vivo in mammalian liver, is independent of changes in levels of serum hormones, which occur in vivo as a result of glucose administration. This study also demonstrates that glucose repression is not mediated by changes in intracellular levels of cAMP and cyclic quanosine 3':5'-monophosphate.", "contents": "Hormonal regulation and the effects of glucose on tyrosine aminotransferase activity in adult rat hepatocytes cultured on floating collagen membranes. Adult rat parenchymal hepatocytes can be maintained in primary culture on floating collagen membranes of prolonged periods of time. In this system the enzyme tyrosine aminotransferase is induced by glucagon, (10(-6) to 10(-8) M) hydrocortisone (10(-5) to 10(-8) M), and cyclic adenosine 3':5'-monophosphate (cAMP) (10(-4) to 10(-5) M). Epinephrine (10(-4) M) induces the enzyme only in the presence of hydrocortisone. Addition of actinomycin D inhibited the induction of tyrosine aminotransferase by hydrocortisone and cAMP. Maintenance of the cultured hepatocytes in the presence of glucose (3g/liter) results in partial suppression of the inducing effects of glucagon and cAMP. Cyclic quanosine 3':5'-monophosphate does not mimic the effects of glucose. These results demonstrate that the phenomenon of glucose repression of enzyme induction, demonstrated in vivo in mammalian liver, is independent of changes in levels of serum hormones, which occur in vivo as a result of glucose administration. This study also demonstrates that glucose repression is not mediated by changes in intracellular levels of cAMP and cyclic quanosine 3':5'-monophosphate."}
{"id": "PMID:25712", "title": "Purification and some properties of Bacillus macerans cycloamylose (cyclodextrin) glucanotransferase.", "content": "Bacillus macerans cycloamylose (cyclodextrin) glucanotransferase (EC 2.4.1.19) was purified by the technique of starch adsorption and DEAE-cellulose column chromatography, and then crystallized from an ammonium sulfate solution containing mM calcium chloride. The crystals of the enzyme were rod-shaped and showed a single band by disc-gel electrophorsis. The purified enzyme was dissociated into two subunits by sodium dodecyl sulfate-disc electrophoresis. The subunits had no enzyme activity. Details of each purification step and some properties of the enzyme are described in this paper.", "contents": "Purification and some properties of Bacillus macerans cycloamylose (cyclodextrin) glucanotransferase. Bacillus macerans cycloamylose (cyclodextrin) glucanotransferase (EC 2.4.1.19) was purified by the technique of starch adsorption and DEAE-cellulose column chromatography, and then crystallized from an ammonium sulfate solution containing mM calcium chloride. The crystals of the enzyme were rod-shaped and showed a single band by disc-gel electrophorsis. The purified enzyme was dissociated into two subunits by sodium dodecyl sulfate-disc electrophoresis. The subunits had no enzyme activity. Details of each purification step and some properties of the enzyme are described in this paper."}
{"id": "PMID:25714", "title": "Evidence for the detrimental effect of adrenaline infused to healthy dogs in doses imitating spontaneous secretion after coronary occlusion.", "content": "We have previously shown that acute coronary occlusion in the dog is often accompanied by increased adrenaline release into the blood. In the present study the consequences of this humoral reaction were studied in anaesthetised healthy mongrel dogs subjected to adrenaline infusion administered at a rate relevant to spontaneous release of this amine in coronary occlusion. Adrenaline was infused in a dose of 1.2 microgram.kg-1.min-1 for 4 h. Dogs receiving saline served as the control. Adrenaline administration led to the decrease in insulin/glucose ratio, to a significant fall in serum triiodothyronine and in blood pH. Free fatty acid levels doubled. Histochemically, a diminution in succinic dehydrogenase and ATPase activity in adrenaline-treated hearts was found. A significant fall in the activity of mitochondrial hexokinase in these hearts was detected spectrophotometrically. Electron microscopic study revealed alterations in the mitochondrial structure. These findings indicate that an excess of adrenaline in ammounts similar to that seen in experimental infarction leads to profound metabolic and hormonal disturbances and exerts a detrimental effect upon myocardium.", "contents": "Evidence for the detrimental effect of adrenaline infused to healthy dogs in doses imitating spontaneous secretion after coronary occlusion. We have previously shown that acute coronary occlusion in the dog is often accompanied by increased adrenaline release into the blood. In the present study the consequences of this humoral reaction were studied in anaesthetised healthy mongrel dogs subjected to adrenaline infusion administered at a rate relevant to spontaneous release of this amine in coronary occlusion. Adrenaline was infused in a dose of 1.2 microgram.kg-1.min-1 for 4 h. Dogs receiving saline served as the control. Adrenaline administration led to the decrease in insulin/glucose ratio, to a significant fall in serum triiodothyronine and in blood pH. Free fatty acid levels doubled. Histochemically, a diminution in succinic dehydrogenase and ATPase activity in adrenaline-treated hearts was found. A significant fall in the activity of mitochondrial hexokinase in these hearts was detected spectrophotometrically. Electron microscopic study revealed alterations in the mitochondrial structure. These findings indicate that an excess of adrenaline in ammounts similar to that seen in experimental infarction leads to profound metabolic and hormonal disturbances and exerts a detrimental effect upon myocardium."}
{"id": "PMID:25715", "title": "Locomotion and neuromuscular system of Aglantha digitale.", "content": "Aglantha digitale swims in two ways: a slow rhythmical swim typical of hydromedusae in general and a sudden rapid movement that appears to be an escape response. The swimming musculature is an extremely well developed striated circular muscle layer that possesses a sarcoplasmic reticulum. The nervous system of this species can be divided into three units: an inner nerve ring and an outer nerve ring, which are joined by unusually large transmesogleal pathways, a group of giant axons that extends over the surface of the swimming muscle, and the radial canal. Well developed ciliated sensory cells are located on the exumbrellar surface of the margin. Consideration of these properties of the organisation of this species suggests that normal slow swimming is controlled by a mechanism similar to that found in other medusae, while the escape response is the result of the action of the giant axons.", "contents": "Locomotion and neuromuscular system of Aglantha digitale. Aglantha digitale swims in two ways: a slow rhythmical swim typical of hydromedusae in general and a sudden rapid movement that appears to be an escape response. The swimming musculature is an extremely well developed striated circular muscle layer that possesses a sarcoplasmic reticulum. The nervous system of this species can be divided into three units: an inner nerve ring and an outer nerve ring, which are joined by unusually large transmesogleal pathways, a group of giant axons that extends over the surface of the swimming muscle, and the radial canal. Well developed ciliated sensory cells are located on the exumbrellar surface of the margin. Consideration of these properties of the organisation of this species suggests that normal slow swimming is controlled by a mechanism similar to that found in other medusae, while the escape response is the result of the action of the giant axons."}
{"id": "PMID:25719", "title": "Takayasu's disease in twin sisters. Possible genetic factors.", "content": "Takayasu's disease is well-known for its characteristic clinical features and its elusive etiology. Recently, we encountered twin Japanese sisters, both of whom were diagnosed as having Takayasu's disease. The parents, two sisters, and one brother are healthy. Family history revealed the parents are first cousins. Analyses of serveral blood types and HLA typing were performed on all members of the family, and it was confirmed that these twins are monozygotic. Moreover, HLA typing analyses revealed that one haplotype found in the father was passed only to these twins. The history of consanguinity of the parents, the occurrence in twins, and the results of HLA typing suggest a genetic factor in the etiology of Takayasu's disease.", "contents": "Takayasu's disease in twin sisters. Possible genetic factors. Takayasu's disease is well-known for its characteristic clinical features and its elusive etiology. Recently, we encountered twin Japanese sisters, both of whom were diagnosed as having Takayasu's disease. The parents, two sisters, and one brother are healthy. Family history revealed the parents are first cousins. Analyses of serveral blood types and HLA typing were performed on all members of the family, and it was confirmed that these twins are monozygotic. Moreover, HLA typing analyses revealed that one haplotype found in the father was passed only to these twins. The history of consanguinity of the parents, the occurrence in twins, and the results of HLA typing suggest a genetic factor in the etiology of Takayasu's disease."}
{"id": "PMID:25720", "title": "Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion.", "content": "Vigorous hyperventilation was induced for five minutes immediately after a five-minute infusion of 100 ml of Tris-buffer (pH 10) in nine patients with Prinzmetal's variant angina. In eight of the patients, chest pain with ischemic changes in the electrocardiogram occurred during this procedure or within five minutes after it ended. Coronary arterial spasm appeared after the procedure and disappeared after the administration of nitroglycerin in all four patients in whom coronary cinearteriography was performed. This was evident both before and after the procedure and after sublingual administration of nitroglycerin (0.6 mg). The oral administration of 90 mg of diltiazem, a calcium antagonistic drug, two hours before, completely suppressed the attack induced by the procedure in all of the five patients who received this drug. We conclude that hyperventilation plus Tris-buffer infusion induces coronary arterial spasm and anginal attack in patients with Prinzmetal's variant angina and that diltiazem suppresses these reactions.", "contents": "Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion. Vigorous hyperventilation was induced for five minutes immediately after a five-minute infusion of 100 ml of Tris-buffer (pH 10) in nine patients with Prinzmetal's variant angina. In eight of the patients, chest pain with ischemic changes in the electrocardiogram occurred during this procedure or within five minutes after it ended. Coronary arterial spasm appeared after the procedure and disappeared after the administration of nitroglycerin in all four patients in whom coronary cinearteriography was performed. This was evident both before and after the procedure and after sublingual administration of nitroglycerin (0.6 mg). The oral administration of 90 mg of diltiazem, a calcium antagonistic drug, two hours before, completely suppressed the attack induced by the procedure in all of the five patients who received this drug. We conclude that hyperventilation plus Tris-buffer infusion induces coronary arterial spasm and anginal attack in patients with Prinzmetal's variant angina and that diltiazem suppresses these reactions."}
{"id": "PMID:25721", "title": "Characteristics of the inhibition of serum alkaline phosphatase by theophylline.", "content": "1. The effect of various parameters on the inhibition of alkaline phosphatase activity by theophylline was studied. The influence of pH is great, being optimum for a value of 9.4. The temperature and the magnesium ion concentration have no to low effect. 2. The nature of the substrate and the nature of the buffer in which the enzymatic activity is measured have an effect:by measuring the activity of alkaline phosphatase in serum by a method with phenolphthaleinphosphate in Tris buffer, a negligible interference by therapeutic or toxic levels of theophylline is observed. 3. The inhibition by theophylline varies greatly with the origin of alkaline phosphatase: the liver isoenzyme is strongly inhibited, the intestinal one to a lesser degree and the placental isoenzyme almost not inhibited. 4. The inhibition of the liver and intestinal isoenzymes are uncompetitive and the inhibition constants were measured.", "contents": "Characteristics of the inhibition of serum alkaline phosphatase by theophylline. 1. The effect of various parameters on the inhibition of alkaline phosphatase activity by theophylline was studied. The influence of pH is great, being optimum for a value of 9.4. The temperature and the magnesium ion concentration have no to low effect. 2. The nature of the substrate and the nature of the buffer in which the enzymatic activity is measured have an effect:by measuring the activity of alkaline phosphatase in serum by a method with phenolphthaleinphosphate in Tris buffer, a negligible interference by therapeutic or toxic levels of theophylline is observed. 3. The inhibition by theophylline varies greatly with the origin of alkaline phosphatase: the liver isoenzyme is strongly inhibited, the intestinal one to a lesser degree and the placental isoenzyme almost not inhibited. 4. The inhibition of the liver and intestinal isoenzymes are uncompetitive and the inhibition constants were measured."}
{"id": "PMID:25722", "title": "A stable blood product for pH-blood-gas quality control.", "content": "We describe how to prepare, store, and use a hemolyzed blood product for simultaneous pH, pCO2, and pO2 quality control. Tonometry of the blood product with two oxygen and two carbon dioxide concentrations resulted in consistent and reproducible values during 38 weeks. The resulting pH values were consistent and reproducible, demonstrating the metabolic acid-base stability of the blood product. We conclude that the proper preparation, storage, and use of the product results in consistent, reproducible, and economical quality control for pH, pCO2 and pO2 blood measurements.", "contents": "A stable blood product for pH-blood-gas quality control. We describe how to prepare, store, and use a hemolyzed blood product for simultaneous pH, pCO2, and pO2 quality control. Tonometry of the blood product with two oxygen and two carbon dioxide concentrations resulted in consistent and reproducible values during 38 weeks. The resulting pH values were consistent and reproducible, demonstrating the metabolic acid-base stability of the blood product. We conclude that the proper preparation, storage, and use of the product results in consistent, reproducible, and economical quality control for pH, pCO2 and pO2 blood measurements."}
{"id": "PMID:25723", "title": "Simultaneous detection and quantitation of drugs commonly involved in self-administered overdoses.", "content": "The system described here is designed for ease of detection and quantitation of tricyclic antidepressants, benzodiazepines, and other tranquilizers now commonly found in self poisoning. An ether extract of serum is purified by acid transfer, back-extracted into ether, dried, and evaporated. The residue is run on a thin-layer plate against standards and inspected under 254-nm light. Depending on requirements, the amount of unknown may then be estimated or further chromatography performed in a different solvent. Quantitation and further confirmation of identity by staining follow. The equipment needed is very simple and many samples can be handled simultaneously and completed within a working day.", "contents": "Simultaneous detection and quantitation of drugs commonly involved in self-administered overdoses. The system described here is designed for ease of detection and quantitation of tricyclic antidepressants, benzodiazepines, and other tranquilizers now commonly found in self poisoning. An ether extract of serum is purified by acid transfer, back-extracted into ether, dried, and evaporated. The residue is run on a thin-layer plate against standards and inspected under 254-nm light. Depending on requirements, the amount of unknown may then be estimated or further chromatography performed in a different solvent. Quantitation and further confirmation of identity by staining follow. The equipment needed is very simple and many samples can be handled simultaneously and completed within a working day."}
{"id": "PMID:25724", "title": "Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C.", "content": "We report optimal conditions for assaying highly purified human lactate dehydrogenase isoenzymes with the lactate-to-pyruvate and pyruvate-to-lactate reactions, as they apply to human serum. Interconversion of results between reactions is not practicable. Measurements of lactate dehydrogenase in either reaction direction at 25, 30, or 37 degrees C can be equally reliable if the volume fraction and the resulting deltaA/min is small. However, for interinstrument and interlaboratory comparisons, results from the lactate-to-pyruvate reaction are more reliable.", "contents": "Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C. We report optimal conditions for assaying highly purified human lactate dehydrogenase isoenzymes with the lactate-to-pyruvate and pyruvate-to-lactate reactions, as they apply to human serum. Interconversion of results between reactions is not practicable. Measurements of lactate dehydrogenase in either reaction direction at 25, 30, or 37 degrees C can be equally reliable if the volume fraction and the resulting deltaA/min is small. However, for interinstrument and interlaboratory comparisons, results from the lactate-to-pyruvate reaction are more reliable."}
{"id": "PMID:25726", "title": "Liquid chromatographic determination of urinary dopamine and norepinephrine as fluorescamine derivatives.", "content": "Dopamine (DM) and norepinephrine (NE) with 3,4-dihydroxybenzylamine as internal standard in normal human urine were extracted with alumina, labeled with fluorescamine and determined fluorometrically by liquid chromatography. The method is simple and in the case of excretion of DM in urines of subjects receiving 1-dopa, even the alumina treatment was unnecessary. The C.V. of method was 4.3% and 4.5% for DM and NE, respectively. The mean contents of DM and NE in 7 normal urines were 182 and 35.5 ng/mg creatinine, respectively.", "contents": "Liquid chromatographic determination of urinary dopamine and norepinephrine as fluorescamine derivatives. Dopamine (DM) and norepinephrine (NE) with 3,4-dihydroxybenzylamine as internal standard in normal human urine were extracted with alumina, labeled with fluorescamine and determined fluorometrically by liquid chromatography. The method is simple and in the case of excretion of DM in urines of subjects receiving 1-dopa, even the alumina treatment was unnecessary. The C.V. of method was 4.3% and 4.5% for DM and NE, respectively. The mean contents of DM and NE in 7 normal urines were 182 and 35.5 ng/mg creatinine, respectively."}
{"id": "PMID:25727", "title": "Characterization of the acid beta-D-galactosidases from human urine.", "content": "Acid beta-D-galactosidases (EC 3.2.1.23) from human urine samples have been characterized using GM1-ganglioside, asialofetuin, and 4-MU-beta-D galactopyranoside. Sepharose 6-B column chromatography of crude urine supernatant fluids resolved three forms of acid beta-D-galactosidase activity with apparent molecular weights of 500 X 10(3)--700 X 10(3) (I), 90 X 10(3)--120 X 10(3) (II), and 20 X 10(3)--27 X 10(3) (III), which hydrolyzed 4-MU-beta-D-galactopyranoside, GM1-ganglioside and asialofetuin. The crude urine supernatant fluids and the separated forms of acid beta-D-galactosidase exhibited similar apparent KM values for the respective substrates. Starch gel electrophoresis of urine samples at pH 7.0 revealed a slow anodally migrating form of acid beta-D-galactosidase which electrophoretically corresponded to form I and a faster anodally migrating form corresponding to form II. Form III migrated as a composite of forms I and II suggesting that aggregation to the larger molecular weight activity forms occurred during starch gel electrophoresis. This report represents the first characterization of urinary acid beta-D-galactosidase with respect to naturally occurring glycolipid and glycoprotein substrates. In addition, data is presented to indicate that the enzyme may be composed of an enzymatically active form with an apparent molecular weight of 20 X 10(3)--27 X10(3), which is also capable of hydrolyzing the glycolipid and glycoprotein substrates.", "contents": "Characterization of the acid beta-D-galactosidases from human urine. Acid beta-D-galactosidases (EC 3.2.1.23) from human urine samples have been characterized using GM1-ganglioside, asialofetuin, and 4-MU-beta-D galactopyranoside. Sepharose 6-B column chromatography of crude urine supernatant fluids resolved three forms of acid beta-D-galactosidase activity with apparent molecular weights of 500 X 10(3)--700 X 10(3) (I), 90 X 10(3)--120 X 10(3) (II), and 20 X 10(3)--27 X 10(3) (III), which hydrolyzed 4-MU-beta-D-galactopyranoside, GM1-ganglioside and asialofetuin. The crude urine supernatant fluids and the separated forms of acid beta-D-galactosidase exhibited similar apparent KM values for the respective substrates. Starch gel electrophoresis of urine samples at pH 7.0 revealed a slow anodally migrating form of acid beta-D-galactosidase which electrophoretically corresponded to form I and a faster anodally migrating form corresponding to form II. Form III migrated as a composite of forms I and II suggesting that aggregation to the larger molecular weight activity forms occurred during starch gel electrophoresis. This report represents the first characterization of urinary acid beta-D-galactosidase with respect to naturally occurring glycolipid and glycoprotein substrates. In addition, data is presented to indicate that the enzyme may be composed of an enzymatically active form with an apparent molecular weight of 20 X 10(3)--27 X10(3), which is also capable of hydrolyzing the glycolipid and glycoprotein substrates."}
{"id": "PMID:25728", "title": "Lipoprotein-X and diagnosis of cholestasis: comparison with other biochemical parameters and liver biopsy.", "content": "The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in gamma-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-X formation and the possible relationships between LP-X and gamma-glutamyl transpeptidase.", "contents": "Lipoprotein-X and diagnosis of cholestasis: comparison with other biochemical parameters and liver biopsy. The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in gamma-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-X formation and the possible relationships between LP-X and gamma-glutamyl transpeptidase."}
{"id": "PMID:25729", "title": "Studies on alkaline phosphatase isoenzymes in hepatic diseases. Relation to gamma-glutamyltransferase.", "content": "Isoenzymes of alkaline phosphatase (ALP) and total gamma-glutamyltransferase (gamma GT) have been studied in patients with increased total ALP. Fractionation of alkaline phosphatase yielded clinical information which could not be obtained by determination ALP and gamma GT alone. 1. There was a high degree of correlation between isoALP 1 (biliary band) and total gamma GT. 2. The ALP2 fraction increases after cytolysis in acute and chronic hepatitis. 3. A new ALP4 fraction appears, probably due to fibroblastic activity, in some histological types of cirrhosis.", "contents": "Studies on alkaline phosphatase isoenzymes in hepatic diseases. Relation to gamma-glutamyltransferase. Isoenzymes of alkaline phosphatase (ALP) and total gamma-glutamyltransferase (gamma GT) have been studied in patients with increased total ALP. Fractionation of alkaline phosphatase yielded clinical information which could not be obtained by determination ALP and gamma GT alone. 1. There was a high degree of correlation between isoALP 1 (biliary band) and total gamma GT. 2. The ALP2 fraction increases after cytolysis in acute and chronic hepatitis. 3. A new ALP4 fraction appears, probably due to fibroblastic activity, in some histological types of cirrhosis."}
{"id": "PMID:25730", "title": "A new variant of methylmalonic acidemia-defective coenzyme-apoenzyme binding in cultured fibroblasts.", "content": "Cultured fibroblasts from a patient with methylmalonic acidemia, clinically responsive to vitamin B-12, were studied in vitro. Kinetic analysis revealed abnormal binding of the coenzyme, 5'-deoxyadenosylcobalamin, for its methylmalonyl-CoA carbonylmutase apoenzyme, i.e., KM of 3.8 X 10(-5) M versus control KM of 1.5 X 10(-8) M. These data are interpreted as indicating a structural defect of the apoenzyme at the coenzyme binding site, and represent another variant of this genetic disorder.", "contents": "A new variant of methylmalonic acidemia-defective coenzyme-apoenzyme binding in cultured fibroblasts. Cultured fibroblasts from a patient with methylmalonic acidemia, clinically responsive to vitamin B-12, were studied in vitro. Kinetic analysis revealed abnormal binding of the coenzyme, 5'-deoxyadenosylcobalamin, for its methylmalonyl-CoA carbonylmutase apoenzyme, i.e., KM of 3.8 X 10(-5) M versus control KM of 1.5 X 10(-8) M. These data are interpreted as indicating a structural defect of the apoenzyme at the coenzyme binding site, and represent another variant of this genetic disorder."}
{"id": "PMID:25731", "title": "Immunoreactive properties of anti-thyroglobulin autoantibodies isolated by affinity chromatography from human thyroiditis serum.", "content": "A Sepharose-coupled 19S human thyroglobulin has been used as an immunoadsorbent to isolate anti-thyroglobulin autoantibodies and to evaluate the antigen-antibody interactions. With the system proposed a high yield of active antibody molecules was obtained. It is possible to evaluate both the soluble and precipitating 'immunological interactions', thus avoiding the use of the double antibody technique.", "contents": "Immunoreactive properties of anti-thyroglobulin autoantibodies isolated by affinity chromatography from human thyroiditis serum. A Sepharose-coupled 19S human thyroglobulin has been used as an immunoadsorbent to isolate anti-thyroglobulin autoantibodies and to evaluate the antigen-antibody interactions. With the system proposed a high yield of active antibody molecules was obtained. It is possible to evaluate both the soluble and precipitating 'immunological interactions', thus avoiding the use of the double antibody technique."}
{"id": "PMID:25732", "title": "Increased biliary excretion of ouabain induced by bucolome in the rat.", "content": "1. Following the intravenous injection of 3H-ouabain (0.4 or 0.6 mg/100 g body weight) the plasma concentration and biliary excretion of ouabain were compared for control male Wistar rats and rats given bucolome (BC, 1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydroxypyrimidine, 20 mg/100 g) 40 min before the ouabain injection. In bucolome treated rats, the bile flow rate was 80-90% higher than in control rats and the biliary excretion rate of ouabain for the 40 min post-injection period was significantly higher in bucolome treated rat groups. The increase was due to an approximately two-fold increase in the excretion rate in the first 10 min period. On the other hand, plasma concentration of ouabain was significantly higher in bucolome treated rats compared with control rats at corresponding time intervals. Plasma volume as determined by 131I-labelled albumin dilution was not decreased in bucolome treated rats. 2. The results indicated that the significant increase in biliary excretion of ouabain administration was due to the enhancement of the hepatic transport and/or biliary excretion process and not due to an increase in hepatic uptake.", "contents": "Increased biliary excretion of ouabain induced by bucolome in the rat. 1. Following the intravenous injection of 3H-ouabain (0.4 or 0.6 mg/100 g body weight) the plasma concentration and biliary excretion of ouabain were compared for control male Wistar rats and rats given bucolome (BC, 1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydroxypyrimidine, 20 mg/100 g) 40 min before the ouabain injection. In bucolome treated rats, the bile flow rate was 80-90% higher than in control rats and the biliary excretion rate of ouabain for the 40 min post-injection period was significantly higher in bucolome treated rat groups. The increase was due to an approximately two-fold increase in the excretion rate in the first 10 min period. On the other hand, plasma concentration of ouabain was significantly higher in bucolome treated rats compared with control rats at corresponding time intervals. Plasma volume as determined by 131I-labelled albumin dilution was not decreased in bucolome treated rats. 2. The results indicated that the significant increase in biliary excretion of ouabain administration was due to the enhancement of the hepatic transport and/or biliary excretion process and not due to an increase in hepatic uptake."}
{"id": "PMID:25745", "title": "Bullous papular urticaria.", "content": "A bullous type of papular urticaria is seen commonly in Iraq. The eruption can be extensive, simulating some of the more serious bullous skin diseases. This paper describes the condition clinically and histologically.", "contents": "Bullous papular urticaria. A bullous type of papular urticaria is seen commonly in Iraq. The eruption can be extensive, simulating some of the more serious bullous skin diseases. This paper describes the condition clinically and histologically."}
{"id": "PMID:25749", "title": "Streptococcus pneumoniae isolates relatively insensitive to penicillin G recovered from patients in Switzerland.", "content": "The sensitivity to penicillin G of pneumococci isolated in Switzerland has been determined by the quantitative tube dilution method. 3 out of 100 strains were relatively insensitive to this antibiotic (minimum inhibitory concentration greater than 0.1 microgram/ml), thus confirming observations already made in other countries. These results underline the necessity of routinely testing the sensitivity of pneumococci to penicillin G.", "contents": "Streptococcus pneumoniae isolates relatively insensitive to penicillin G recovered from patients in Switzerland. The sensitivity to penicillin G of pneumococci isolated in Switzerland has been determined by the quantitative tube dilution method. 3 out of 100 strains were relatively insensitive to this antibiotic (minimum inhibitory concentration greater than 0.1 microgram/ml), thus confirming observations already made in other countries. These results underline the necessity of routinely testing the sensitivity of pneumococci to penicillin G."}
{"id": "PMID:25754", "title": "[Surgery of pancreatic endocrine tumours in the German Federal Republic: results of a survey (author's transl)].", "content": "Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumors, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice.", "contents": "[Surgery of pancreatic endocrine tumours in the German Federal Republic: results of a survey (author's transl)]. Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumors, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice."}
{"id": "PMID:25757", "title": "Labetalol: a review of its pharmacology and therapeutic use in hypertension.", "content": "Labetalol is an orally active adrenoceptor blocking drug which is a competitive antagonist at both alpha- and beta-adrenoceptor sites. Its beta-blocking effects resemble those of propranolol, but its overall haemodynamic effects are akin to those of a comination of propranolol and an alpha-adrenoceptor blocking drugs such as phenoxybenzamine. Unlike with conventional beta-adrenoceptor blocking drugs, acute administration of labetalol reduces peripheral vascular resistance and blood pressure and has little effect on cardiac output. Theoretically, labetalol has advantages over beta-adrenoceptor blocking drugs alone in the treatment of hypertension, but any real advantage, particulary in mild or moderate hypertension, has yet to be conclusively demonstrated in therapeutic trials. Labetalol may be particularly useful in some patients whose blood pressure is not adequately controlled by beta-adrenoceptor blocking drugs alone or combined with a diuretic, but possibly at the expense of a postural hypotensive effect. Postural hypotension is the most troublesome side-effect, occasionally necessitating withdrawal of therapy, but severe side-effects such as are seen with effective antihypertensive dosages of phenoxybenzamine do not occur with labetalol.", "contents": "Labetalol: a review of its pharmacology and therapeutic use in hypertension. Labetalol is an orally active adrenoceptor blocking drug which is a competitive antagonist at both alpha- and beta-adrenoceptor sites. Its beta-blocking effects resemble those of propranolol, but its overall haemodynamic effects are akin to those of a comination of propranolol and an alpha-adrenoceptor blocking drugs such as phenoxybenzamine. Unlike with conventional beta-adrenoceptor blocking drugs, acute administration of labetalol reduces peripheral vascular resistance and blood pressure and has little effect on cardiac output. Theoretically, labetalol has advantages over beta-adrenoceptor blocking drugs alone in the treatment of hypertension, but any real advantage, particulary in mild or moderate hypertension, has yet to be conclusively demonstrated in therapeutic trials. Labetalol may be particularly useful in some patients whose blood pressure is not adequately controlled by beta-adrenoceptor blocking drugs alone or combined with a diuretic, but possibly at the expense of a postural hypotensive effect. Postural hypotension is the most troublesome side-effect, occasionally necessitating withdrawal of therapy, but severe side-effects such as are seen with effective antihypertensive dosages of phenoxybenzamine do not occur with labetalol."}
{"id": "PMID:25760", "title": "[Tear resistance of laser-welded dental alloys].", "content": "The investigation was undertaken to establish the place of lasers as tools in the dental technical laboratory. Tests were undertaken to study resistance to tears in laser welded dental metal alloys. (Degudent U, Degulor M of Fa. Degussa.) Availabel as laser apparatus were a cw Nd:YAG-laser (400 Watt capacity) and a pulse Nd:YAG-laser (max. 45 pulse energy, 9.2 pulse length). Welding tests on models with both lasers resulted in higher resistance to tears than was achievable by conventional soldering processes. Furthermore it could be shown that in certain alloy compositions, used in our experiments, welding by the cw process resulted in greater resistance to fissuring than by the pulse process. By adopting the alloy as well as the preparation of appliances to the laser process we feel that markedly superior results can be achieved as we describe in this first communication.", "contents": "[Tear resistance of laser-welded dental alloys]. The investigation was undertaken to establish the place of lasers as tools in the dental technical laboratory. Tests were undertaken to study resistance to tears in laser welded dental metal alloys. (Degudent U, Degulor M of Fa. Degussa.) Availabel as laser apparatus were a cw Nd:YAG-laser (400 Watt capacity) and a pulse Nd:YAG-laser (max. 45 pulse energy, 9.2 pulse length). Welding tests on models with both lasers resulted in higher resistance to tears than was achievable by conventional soldering processes. Furthermore it could be shown that in certain alloy compositions, used in our experiments, welding by the cw process resulted in greater resistance to fissuring than by the pulse process. By adopting the alloy as well as the preparation of appliances to the laser process we feel that markedly superior results can be achieved as we describe in this first communication."}
{"id": "PMID:25762", "title": "Effects of subanesthetic concentrations of enflurane on rat pregnancy and early development.", "content": "Anesthetic pollutants in the operating room have been implicated in producing spontaneous abortion in exposed personnel and congenital malformations among their offspring. To test the effects of trace concentrations of enflurane on pregnancy, rats were exposed to two levels (10.7 and 63.7 ppm) of the anesthetic for 8 hr daily from days 1 to 19 of pregnancy. Litter sizes were not affected but birth weights of exposed offspring were slightly higher than controls. During lactation, cross-fostering studies were performed. Exposed offspring were housed with nonexposed mothers and vice versa to determine if exposure during pregnancy affected early development. Weights at 7, 14, and 21 days of age did not differ among the offspring in the lower dose experiment. Weights of the cross-fostered groups in the high dose experiment were decreased at day seven compared to controls. In the same experiment, exposed offspring housed with exposed mothers were heavier than controls on day 21 of lactation. The modest nature of these alterations suggests that enflurane has little or no gross effect on rat pregnancy and postnatal development.", "contents": "Effects of subanesthetic concentrations of enflurane on rat pregnancy and early development. Anesthetic pollutants in the operating room have been implicated in producing spontaneous abortion in exposed personnel and congenital malformations among their offspring. To test the effects of trace concentrations of enflurane on pregnancy, rats were exposed to two levels (10.7 and 63.7 ppm) of the anesthetic for 8 hr daily from days 1 to 19 of pregnancy. Litter sizes were not affected but birth weights of exposed offspring were slightly higher than controls. During lactation, cross-fostering studies were performed. Exposed offspring were housed with nonexposed mothers and vice versa to determine if exposure during pregnancy affected early development. Weights at 7, 14, and 21 days of age did not differ among the offspring in the lower dose experiment. Weights of the cross-fostered groups in the high dose experiment were decreased at day seven compared to controls. In the same experiment, exposed offspring housed with exposed mothers were heavier than controls on day 21 of lactation. The modest nature of these alterations suggests that enflurane has little or no gross effect on rat pregnancy and postnatal development."}
{"id": "PMID:25763", "title": "Metabolism and toxicity of 2,2,2-trifluoroethyl vinyl ether.", "content": "A review on metabolism and toxicity of the fluorinated anesthetic agent, fluroxene, is presented. Fluroxene anesthesia is nontoxic to man but fatal to many experimental animals. The fluroxene molecule (2,2,2-trifluroethyl vinyl ether) is composed of two moieties; both are toxic as a result of their metabolism: the vinyl moiety destroys heme of cytochrome P-450 while being metabolized to the final product, CO2. The trifluoroethyl moiety is oxidized to trifluoroethanol (TFE) and trifluoroacetic acid (TFAA), and the acute toxicity of fluroxene is related to this pathway. The ratio of metabolities (TFAA to TFE) excreted by different species exposed to fluroxene varies; whenever highly toxic TFE is the major metabolite, fluroxene toxicity is high (rodents, dogs, phenobarbital pretreated monkeys), whenever TFAA is the major metabolite (man, monkey) fluroxene is not toxic. Toxicity in different species also correlates with the extent of glutathione depletion following fluroxene exposure. Fluroxene metabolism and toxicity are modified by drugs metabolized by or affecting the activity of the microsomal cytochrome P-450-system or enzymes involved in ethanol metabolism. The susceptibility of fluroxene to two enzymatic systems which are modified by environmental and genetic factors may explain the large differences in fluroxene toxicity to various species. The fate of one-third of fluroxene administered to man remains unknown.", "contents": "Metabolism and toxicity of 2,2,2-trifluoroethyl vinyl ether. A review on metabolism and toxicity of the fluorinated anesthetic agent, fluroxene, is presented. Fluroxene anesthesia is nontoxic to man but fatal to many experimental animals. The fluroxene molecule (2,2,2-trifluroethyl vinyl ether) is composed of two moieties; both are toxic as a result of their metabolism: the vinyl moiety destroys heme of cytochrome P-450 while being metabolized to the final product, CO2. The trifluoroethyl moiety is oxidized to trifluoroethanol (TFE) and trifluoroacetic acid (TFAA), and the acute toxicity of fluroxene is related to this pathway. The ratio of metabolities (TFAA to TFE) excreted by different species exposed to fluroxene varies; whenever highly toxic TFE is the major metabolite, fluroxene toxicity is high (rodents, dogs, phenobarbital pretreated monkeys), whenever TFAA is the major metabolite (man, monkey) fluroxene is not toxic. Toxicity in different species also correlates with the extent of glutathione depletion following fluroxene exposure. Fluroxene metabolism and toxicity are modified by drugs metabolized by or affecting the activity of the microsomal cytochrome P-450-system or enzymes involved in ethanol metabolism. The susceptibility of fluroxene to two enzymatic systems which are modified by environmental and genetic factors may explain the large differences in fluroxene toxicity to various species. The fate of one-third of fluroxene administered to man remains unknown."}
{"id": "PMID:25764", "title": "A case of spermatic arteriovenous anastomosis in the horse.", "content": "A large anastomosis of the spermatic artery and vein is described. This was found while surgically removing an abdominal testis. Before surgery the animal wanted to rear after exercise and could not stand on 3 legs for any length of time while being shod. This unusual behaviour disappeared after removal of the mass. The performance and conformation of the horse has also greatly improved.", "contents": "A case of spermatic arteriovenous anastomosis in the horse. A large anastomosis of the spermatic artery and vein is described. This was found while surgically removing an abdominal testis. Before surgery the animal wanted to rear after exercise and could not stand on 3 legs for any length of time while being shod. This unusual behaviour disappeared after removal of the mass. The performance and conformation of the horse has also greatly improved."}
{"id": "PMID:25765", "title": "Studies on the purification and properties of a 6.8-S DNA polymerase activity found in calf-thymus DNA polymerase-alpha fraction.", "content": "The heterogeneity of calf thymus DNA polymerase-alpha has been further investigated. In particular, an enzyme (enzyme D) which exhibits higher activity on poly(dA) . (dT)10 (A:T = 20:1) compared with that on activated DNA, has been further purified and its properties compared with two other activities of the DNA polymerase-alpha fraction (enzymes A1 and C) which do not show a preference for poly(dA) . (dT)10 over activated DNA. As with A1 and C, enzyme D was shown to have many of the characteristic properties of DNA polymerase-alpha in that it is an acidic protein as judged by its binding to DEAE-cellulose, has a molecular weight of about 140000, does not use a poly (A) . (dT)10 template-initiator complex and is inhibited by N-ethylmaleimide. It exhibits anomalous gel filtration behaviour on Sepharose 6B and it binds relatively weakly to DNA-cellulose compared with DNA polymerase-beta. The extreme sensitivity of enzyme D to inhibtion by N-ethylmaleimide distinguishes it from A1 and C, as does its elution position from a DEAE-cellulose column. On the other hand enzymes C and D are readily inactivated by heating at 45 degrees C unlike enzyme A1. The possible interrelationships of the multiple activities of calf thymus DNA polymerase-alpha are discussed.", "contents": "Studies on the purification and properties of a 6.8-S DNA polymerase activity found in calf-thymus DNA polymerase-alpha fraction. The heterogeneity of calf thymus DNA polymerase-alpha has been further investigated. In particular, an enzyme (enzyme D) which exhibits higher activity on poly(dA) . (dT)10 (A:T = 20:1) compared with that on activated DNA, has been further purified and its properties compared with two other activities of the DNA polymerase-alpha fraction (enzymes A1 and C) which do not show a preference for poly(dA) . (dT)10 over activated DNA. As with A1 and C, enzyme D was shown to have many of the characteristic properties of DNA polymerase-alpha in that it is an acidic protein as judged by its binding to DEAE-cellulose, has a molecular weight of about 140000, does not use a poly (A) . (dT)10 template-initiator complex and is inhibited by N-ethylmaleimide. It exhibits anomalous gel filtration behaviour on Sepharose 6B and it binds relatively weakly to DNA-cellulose compared with DNA polymerase-beta. The extreme sensitivity of enzyme D to inhibtion by N-ethylmaleimide distinguishes it from A1 and C, as does its elution position from a DEAE-cellulose column. On the other hand enzymes C and D are readily inactivated by heating at 45 degrees C unlike enzyme A1. The possible interrelationships of the multiple activities of calf thymus DNA polymerase-alpha are discussed."}
{"id": "PMID:25766", "title": "Sulfate-mediated affinity chromatography on NADP+-Sepharose of glutamate dehydrogenase from halophilic bacteria and of glucose-6-phosphate dehydrogenase from Escherichia coli.", "content": "An improved synthesis of the 8-(6-aminohexyl)amino derivative of NADP+ is described for use in affinity chromatography. The binding of glutamate dehydrogenase isolated from halobacterium of the Dead Sea on a column of Sepharose linked to this NADP+ derivative could be drastically enhanced by addition of sulfate (1M) and provided a tool for partially purifying the enzyme from a crude extract. A similar finding is reported for glucose-6-phosphate dehydrogenase in crude extracts of Escherichia coli. The effects are shown to be biospecific, suggesting that the strength of the interaction between protein and immobilized coenzymes is a function of the sulfate concentration.", "contents": "Sulfate-mediated affinity chromatography on NADP+-Sepharose of glutamate dehydrogenase from halophilic bacteria and of glucose-6-phosphate dehydrogenase from Escherichia coli. An improved synthesis of the 8-(6-aminohexyl)amino derivative of NADP+ is described for use in affinity chromatography. The binding of glutamate dehydrogenase isolated from halobacterium of the Dead Sea on a column of Sepharose linked to this NADP+ derivative could be drastically enhanced by addition of sulfate (1M) and provided a tool for partially purifying the enzyme from a crude extract. A similar finding is reported for glucose-6-phosphate dehydrogenase in crude extracts of Escherichia coli. The effects are shown to be biospecific, suggesting that the strength of the interaction between protein and immobilized coenzymes is a function of the sulfate concentration."}
{"id": "PMID:25768", "title": "Affinity labelling of the estrogen binding site of glutamate dehydrogenase with iodoacetyldiethylstilbestrol. Selective alkylation of cysteine-89.", "content": "Iodoacetyldiethylstilbestrol was used as an affinity label to alkylate the estrogen binding site of bovine liver glutamate dehydrogenase. This reagent induced inactivation and alkylation of the enzyme. The non-alkylating analogues diethylstilbestrol and estradiol protected the enzyme towards alkylation. The apparent constant of alkylation was of the order of magnitude of I50 for the allosteric inhibition by diethylstilbestrol. These two results suggest that alkylation occurred at the estrogen binding site. The stoichiometry of alkylation was between one and two, depending on the experimental conditions. When the stoichiometry was found to be less than or equal to 1, 90% of the label was bound on cystein residues, 70% of which was carried by cysteine-89, a cysteine residue which is known to be inacessible to iodoacetamide in phosphate buffer in the same conditions of temperature and pH.", "contents": "Affinity labelling of the estrogen binding site of glutamate dehydrogenase with iodoacetyldiethylstilbestrol. Selective alkylation of cysteine-89. Iodoacetyldiethylstilbestrol was used as an affinity label to alkylate the estrogen binding site of bovine liver glutamate dehydrogenase. This reagent induced inactivation and alkylation of the enzyme. The non-alkylating analogues diethylstilbestrol and estradiol protected the enzyme towards alkylation. The apparent constant of alkylation was of the order of magnitude of I50 for the allosteric inhibition by diethylstilbestrol. These two results suggest that alkylation occurred at the estrogen binding site. The stoichiometry of alkylation was between one and two, depending on the experimental conditions. When the stoichiometry was found to be less than or equal to 1, 90% of the label was bound on cystein residues, 70% of which was carried by cysteine-89, a cysteine residue which is known to be inacessible to iodoacetamide in phosphate buffer in the same conditions of temperature and pH."}
{"id": "PMID:25769", "title": "Purification, biochemical and immunological characterisation of hexosaminidase A from variant AB of infantile GM2 gangliosidosis.", "content": "Variant AB of infantile GM2 gangliosidosis is a fatal disease leading invariably to death within the first few years of life, due to the excessive storage of the glycolipids GM2 and GA2 which occurs in the nervous tissue of the patient. Unlike other variants of this hereditary disease, where a deficiency of hexosaminidase A, the ganglioside-GM2-degrading enzyme, could be demonstrated, the variant AB is characterized by a normal or even elevated level of this enzyme. To examine the possibility of a mutant hexosaminidase A, well capable of hydrolyzing the fluorogenic synthetic substrates but unable to attack the ganglioside, the enzyme was isolated from a patients tissue and characterized biochemically and immunologically in comparison with an enzyme preparation from normal control tissue. No differences between hexosaminidase A from normal and variant AB tissue could be detected indicating that the defect involved in this disease is not at the genetic level of production of either alpha or beta chains of hexosaminidase A.", "contents": "Purification, biochemical and immunological characterisation of hexosaminidase A from variant AB of infantile GM2 gangliosidosis. Variant AB of infantile GM2 gangliosidosis is a fatal disease leading invariably to death within the first few years of life, due to the excessive storage of the glycolipids GM2 and GA2 which occurs in the nervous tissue of the patient. Unlike other variants of this hereditary disease, where a deficiency of hexosaminidase A, the ganglioside-GM2-degrading enzyme, could be demonstrated, the variant AB is characterized by a normal or even elevated level of this enzyme. To examine the possibility of a mutant hexosaminidase A, well capable of hydrolyzing the fluorogenic synthetic substrates but unable to attack the ganglioside, the enzyme was isolated from a patients tissue and characterized biochemically and immunologically in comparison with an enzyme preparation from normal control tissue. No differences between hexosaminidase A from normal and variant AB tissue could be detected indicating that the defect involved in this disease is not at the genetic level of production of either alpha or beta chains of hexosaminidase A."}
{"id": "PMID:25772", "title": "Conversion of the active-site cysteine residue of papain into a dehydro-serine, a serine and a glycine residue.", "content": "Photolysis of papain which had been inhibited with 2-bromo-2',4'-dimethoxyacetophenone regenerated papain, but also formed [deltaSer25]-papain (i.e. papain in which the active-site cysteine residue 25 was replaced by dehydroserine) via the intermediate dehydrocysteine analogue, [deltaCys25]-papain. Reduction with sodium borohydride gave [Ser25]papain. Both [Ser25]papain and [deltaSer25]-papain had binding properties similar to those of papain, but were devoid of enzymic activity. Their fluorescence properties were also investigated. Incubation of [deltaSer25]papain at pH 9.0 gave [Gly25]papain.", "contents": "Conversion of the active-site cysteine residue of papain into a dehydro-serine, a serine and a glycine residue. Photolysis of papain which had been inhibited with 2-bromo-2',4'-dimethoxyacetophenone regenerated papain, but also formed [deltaSer25]-papain (i.e. papain in which the active-site cysteine residue 25 was replaced by dehydroserine) via the intermediate dehydrocysteine analogue, [deltaCys25]-papain. Reduction with sodium borohydride gave [Ser25]papain. Both [Ser25]papain and [deltaSer25]-papain had binding properties similar to those of papain, but were devoid of enzymic activity. Their fluorescence properties were also investigated. Incubation of [deltaSer25]papain at pH 9.0 gave [Gly25]papain."}
{"id": "PMID:25775", "title": "Bovine lenticular gamma-glutamylcysteine synthetase: reaction sequence.", "content": "The sequence of substrate addition and product release during the reaction catalyzed by gamma-glutamylcysteine synthetase was investigated with purified enzyme from bovine lens. Thermal inactivation and kinetic studies suggest that L-glutamate is the first substrate to bind to the enzyme. L-beta-Chloroalanine was used as the L-cysteine analogue. Utilizing substrate activation and product inhibition studies, the following reaction sequence was determined: L-glutamate binding. ATP binding, ADP release, L-beta-chloroalanine binding, followed by inorganic phosphate and then dipeptide release. The implications of this mechanism with regard to control of the enzyme in situ and its importance in glutathione synthesis are discussed.", "contents": "Bovine lenticular gamma-glutamylcysteine synthetase: reaction sequence. The sequence of substrate addition and product release during the reaction catalyzed by gamma-glutamylcysteine synthetase was investigated with purified enzyme from bovine lens. Thermal inactivation and kinetic studies suggest that L-glutamate is the first substrate to bind to the enzyme. L-beta-Chloroalanine was used as the L-cysteine analogue. Utilizing substrate activation and product inhibition studies, the following reaction sequence was determined: L-glutamate binding. ATP binding, ADP release, L-beta-chloroalanine binding, followed by inorganic phosphate and then dipeptide release. The implications of this mechanism with regard to control of the enzyme in situ and its importance in glutathione synthesis are discussed."}
{"id": "PMID:25777", "title": "Acid-base and gas tension of cerebrospinal fluid in Nigerians and tetanus patients.", "content": "The acid-base balance and gas tension of the cerebrospinal fluid of eight tetanus patients and twelve control subjects were studied. Tetanus patients had metabolic acidosis which was severely reflected in the cerebrospinal fluid. While the cerebrospinal fluid pH is lower than that of the arterial blood there was no difference between the acid-base and gas tension of the cerebrospinal fluid of Nigerians and the causasians. The severe metabolic acidosis of the cerebrospinal fluid of tetanus patients might be one of the causes of sudden deaths seen in these patients.", "contents": "Acid-base and gas tension of cerebrospinal fluid in Nigerians and tetanus patients. The acid-base balance and gas tension of the cerebrospinal fluid of eight tetanus patients and twelve control subjects were studied. Tetanus patients had metabolic acidosis which was severely reflected in the cerebrospinal fluid. While the cerebrospinal fluid pH is lower than that of the arterial blood there was no difference between the acid-base and gas tension of the cerebrospinal fluid of Nigerians and the causasians. The severe metabolic acidosis of the cerebrospinal fluid of tetanus patients might be one of the causes of sudden deaths seen in these patients."}
{"id": "PMID:25778", "title": "Stereoselective interaction of tetrahydroisoquinolines in beta-adrenoceptor systems.", "content": "In selected beta1- (heart, lipolysis) and beta2-adrenoceptor (trachea) systems, the interaction of racemic-trimetoquinol (TMQ) and the erythro- and threo-diastereomers of 1-(3',4',5'-trimethoxy-alpha-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (alpha-hydroxy TMQ) was investigated. Each tetrahydroisoquinoline possessed agonist activity in these beta-adrenoceptor systems. The rank order of potency observed for these compounds was racemic-TMQ greater than erythro-alpha-hydroxy TMQ greater than threo-alpha-hydroxy TMQ. Using isolated fat adipocytes, a favorable correlation was observed between the elevation in c-AMP and pharmacological response for the TMQ stereoisomers and diastereomers of alpha-hydroxy TMQ. The rise in intracellular c-AMP produced by (-)- and (+)-TMQ in fat cells was blocked by the presence of propranolol, and not in the presence of phentolamine. Since considerably higher concentrations (greater 10(-4) M) of these compounds were required to produce a significant inhibition of c-AMP phosphodiesterase activity in adipose tissue, it is proposed that the lipolytic response is a result of stereoselective interaction of these tetrahydroisoquinolines at the level of membrane-bound adenylate cyclase.", "contents": "Stereoselective interaction of tetrahydroisoquinolines in beta-adrenoceptor systems. In selected beta1- (heart, lipolysis) and beta2-adrenoceptor (trachea) systems, the interaction of racemic-trimetoquinol (TMQ) and the erythro- and threo-diastereomers of 1-(3',4',5'-trimethoxy-alpha-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (alpha-hydroxy TMQ) was investigated. Each tetrahydroisoquinoline possessed agonist activity in these beta-adrenoceptor systems. The rank order of potency observed for these compounds was racemic-TMQ greater than erythro-alpha-hydroxy TMQ greater than threo-alpha-hydroxy TMQ. Using isolated fat adipocytes, a favorable correlation was observed between the elevation in c-AMP and pharmacological response for the TMQ stereoisomers and diastereomers of alpha-hydroxy TMQ. The rise in intracellular c-AMP produced by (-)- and (+)-TMQ in fat cells was blocked by the presence of propranolol, and not in the presence of phentolamine. Since considerably higher concentrations (greater 10(-4) M) of these compounds were required to produce a significant inhibition of c-AMP phosphodiesterase activity in adipose tissue, it is proposed that the lipolytic response is a result of stereoselective interaction of these tetrahydroisoquinolines at the level of membrane-bound adenylate cyclase."}
{"id": "PMID:25779", "title": "Effect of progesterone on adrenoceptors in the isthmus of the rabbit oviduct.", "content": "The effect of adrenergic agonists on the contractility of circular muscle of the isthmus of the oviduct was studied in isolated tissues from rabbits in estrus and after progesterone pretreatment. alpha-Adrenoceptor sensitivity was not altered by progesterone, and the order of potencies of alpha-agonists was similar to that for alpha-adrenoceptors in other rabbit tissues. Progesterone pretreatment increased the maximal inhibitory effect of isoprenaline on beta-adrenoceptors, but did not alter sensitivity to the agonist, suggesting that there had been an increase in the number of beta-adrenoceptors rather than a change in their affinity. The order of potencies of beta-agonists was similar to that for the beta1-adrenoceptor in other rabbit tissues.", "contents": "Effect of progesterone on adrenoceptors in the isthmus of the rabbit oviduct. The effect of adrenergic agonists on the contractility of circular muscle of the isthmus of the oviduct was studied in isolated tissues from rabbits in estrus and after progesterone pretreatment. alpha-Adrenoceptor sensitivity was not altered by progesterone, and the order of potencies of alpha-agonists was similar to that for alpha-adrenoceptors in other rabbit tissues. Progesterone pretreatment increased the maximal inhibitory effect of isoprenaline on beta-adrenoceptors, but did not alter sensitivity to the agonist, suggesting that there had been an increase in the number of beta-adrenoceptors rather than a change in their affinity. The order of potencies of beta-agonists was similar to that for the beta1-adrenoceptor in other rabbit tissues."}
{"id": "PMID:25782", "title": "Does cytoplasmic alkalinization trigger mitochondrial energy dissipation in the brown adipocyte?", "content": "Indirect calorimetry measurements showed that brown fat thermogenesis was very sensitive to modifications of intra-cellular pH induced by extracellular acid-base perturbations. Specific blockage of active Na-K transport by ouabain inhibited the thermogenic response only in acidosis and more efficiently when the glycoside was administered before the catecholamine stimulus than when it was added after the full calorigenic response had developed. It is suggested that the catecholamine stimulus might initiate a positive feed-back alkalinization of the cytoplasm, concomitant with activation of Na-K transport.", "contents": "Does cytoplasmic alkalinization trigger mitochondrial energy dissipation in the brown adipocyte? Indirect calorimetry measurements showed that brown fat thermogenesis was very sensitive to modifications of intra-cellular pH induced by extracellular acid-base perturbations. Specific blockage of active Na-K transport by ouabain inhibited the thermogenic response only in acidosis and more efficiently when the glycoside was administered before the catecholamine stimulus than when it was added after the full calorigenic response had developed. It is suggested that the catecholamine stimulus might initiate a positive feed-back alkalinization of the cytoplasm, concomitant with activation of Na-K transport."}
{"id": "PMID:25783", "title": "Control of non-shivering thermogenesis in a hibernator.", "content": "Present experiments indicate that in hedgehogs two different control mechanisms of non-shivering thermogenesis (NST) exist. During arousal from hibernation catecholamines control heat production in the interscapular brown adipose tissue. In a non-hibernating state, cold-induced NST is controlled by a desoxycorticosterone-like acting compound. The effector system of this second mode of NST is obviously not the interscapular brown fat but a layer of brown adipose tissue which covers the whole back of the hedgehog.", "contents": "Control of non-shivering thermogenesis in a hibernator. Present experiments indicate that in hedgehogs two different control mechanisms of non-shivering thermogenesis (NST) exist. During arousal from hibernation catecholamines control heat production in the interscapular brown adipose tissue. In a non-hibernating state, cold-induced NST is controlled by a desoxycorticosterone-like acting compound. The effector system of this second mode of NST is obviously not the interscapular brown fat but a layer of brown adipose tissue which covers the whole back of the hedgehog."}
{"id": "PMID:25784", "title": "The \"second messenger\" system in brown adipose tissue of developing rats. Its molecular composition and mechanism of function.", "content": "Our studies of the hormonal receptor system and of the sequence of enzymatic events interconnecting the initial hormonal stimulus to the brown adipocyte with its final subcellular effect are summarized here. The hormone-mediated regulatory pathway consists of the adenyl cyclase and the protein kinase systems; the former is composed of the receptor and catalytic sites, the latter of regulatory and catalytic subunits. Emphasis is given currently to the diversity and characteristics of the individual components of the protein kinase system, since it seems to carry out the ultimate unifying mechanism involved in a variety of hormone-mediated functions, i.e. the phosphorylation of a protein molecule.", "contents": "The \"second messenger\" system in brown adipose tissue of developing rats. Its molecular composition and mechanism of function. Our studies of the hormonal receptor system and of the sequence of enzymatic events interconnecting the initial hormonal stimulus to the brown adipocyte with its final subcellular effect are summarized here. The hormone-mediated regulatory pathway consists of the adenyl cyclase and the protein kinase systems; the former is composed of the receptor and catalytic sites, the latter of regulatory and catalytic subunits. Emphasis is given currently to the diversity and characteristics of the individual components of the protein kinase system, since it seems to carry out the ultimate unifying mechanism involved in a variety of hormone-mediated functions, i.e. the phosphorylation of a protein molecule."}
{"id": "PMID:25790", "title": "[Analysis of the mechanism of action of carbonic acid on tissue chemoreceptors].", "content": "Perfusion of the small intestine of anesthetized cats with a solution imitating metabolic acidosis (pH = 7.3; [HCO-3] = =20.2 mM; PCO2 = 38 mm Hg) produced a threshold reflex increase in the blood pressure. The subsequent decrease of [HCO-3] to 3.2 mM and pH to 6.5 evoked a gradual raise of the blood pressure followed by a sharp increase of pressor reflexes amplitude within the range of pH 6.5--6.3. Solutions imitating metabolic acidosis (pH = 7.1; [HCO-3] = 12.7 mM) were found to increase the concentration of H+ ions in the outflow perfusate and blood pressure to larger extent than solutions imitating respiratory acidosis (pH = 7.1; PCO2 = 75 mm Hg). If the solution pH was held constantly at 7.4 by simultaneous decreasing PCO2 and [HCO-3] by a factor of two, a reflex increase in the blood pressure and decrease of perfusate pH had no effect either on blood pressure or perfusate pH. The data obtained suggest that one of the primary determinants of different responses of the tissue chemoreceptors to CO2 is the interstitial pH.", "contents": "[Analysis of the mechanism of action of carbonic acid on tissue chemoreceptors]. Perfusion of the small intestine of anesthetized cats with a solution imitating metabolic acidosis (pH = 7.3; [HCO-3] = =20.2 mM; PCO2 = 38 mm Hg) produced a threshold reflex increase in the blood pressure. The subsequent decrease of [HCO-3] to 3.2 mM and pH to 6.5 evoked a gradual raise of the blood pressure followed by a sharp increase of pressor reflexes amplitude within the range of pH 6.5--6.3. Solutions imitating metabolic acidosis (pH = 7.1; [HCO-3] = 12.7 mM) were found to increase the concentration of H+ ions in the outflow perfusate and blood pressure to larger extent than solutions imitating respiratory acidosis (pH = 7.1; PCO2 = 75 mm Hg). If the solution pH was held constantly at 7.4 by simultaneous decreasing PCO2 and [HCO-3] by a factor of two, a reflex increase in the blood pressure and decrease of perfusate pH had no effect either on blood pressure or perfusate pH. The data obtained suggest that one of the primary determinants of different responses of the tissue chemoreceptors to CO2 is the interstitial pH."}
{"id": "PMID:25791", "title": "[Excretory function of the kidney after denervation and the administration of a beta-blockader].", "content": "Osmotic diuresis (15% mannitol, 4.5 ml/hr) was in duced in anesthetized rats. At the end of each of 10 consecutive 10-min clearance periods the following parameters were determined: diuresis, sodium, chlorine and osmotic excretion, GFR (inulin clearance). The animals were divided into three groups: a) controls, b) with bilateral renal denervation (performed one week earlier) and c) with application of beta-adrenergic blocking agent propranolol (Obsidan, Germed DDR) introduced intravenously 0.1 mg/100 g initially and 0.12 mg/100 g sustaining dose during 2 hrs. The experimental results showed an increased sodium excretion in denervated and obsidan--treated animals with no change of the total excreted osmotically active substances. In denervated animals the chlorine excretion was increased as well. The data suggest that, in osmotic diuresis, the renal denervation and beta-adrenergic blocking agents inhibit the tubular sodium transport. The kidney osmoregulatory functions remains unchanged.", "contents": "[Excretory function of the kidney after denervation and the administration of a beta-blockader]. Osmotic diuresis (15% mannitol, 4.5 ml/hr) was in duced in anesthetized rats. At the end of each of 10 consecutive 10-min clearance periods the following parameters were determined: diuresis, sodium, chlorine and osmotic excretion, GFR (inulin clearance). The animals were divided into three groups: a) controls, b) with bilateral renal denervation (performed one week earlier) and c) with application of beta-adrenergic blocking agent propranolol (Obsidan, Germed DDR) introduced intravenously 0.1 mg/100 g initially and 0.12 mg/100 g sustaining dose during 2 hrs. The experimental results showed an increased sodium excretion in denervated and obsidan--treated animals with no change of the total excreted osmotically active substances. In denervated animals the chlorine excretion was increased as well. The data suggest that, in osmotic diuresis, the renal denervation and beta-adrenergic blocking agents inhibit the tubular sodium transport. The kidney osmoregulatory functions remains unchanged."}
{"id": "PMID:25799", "title": "Rapid assays of urinary estriol in pregnant women.", "content": "Two devices designed for rapid assay of urinary estriol, the E3 KIT and E3 HAIR KIT, were evaluated using urine samples taken from pregnant women. Additionally, the clinical application of these devices in pregnancy management was examined. Correlations were high between an established method and the E3 KIT method (r = 0.819, p less than 0.001) and between the E3 HAIR KIT method and the E3 KIT method ( r = 0.936, p less than 0.01). E3 HAIR KIT assays showing E3 values of less than 20 microgram/ml (positive at 100-fold dilution of the urine) after the 36th week of pregnancy suggested fetoplacental dysfunction and indicated that more detailed tests were required. The E3 KIT, which provided rapid quantitative assay of urinary estriol, was capable of measuring 10 samples in approximately 3 hours. The E3 HAIR KIT provided semiquantitative assays of 10 samples in 2 hours. The speed, simplicity, and accuracy of the E3 HAIR KIT indicates its high clinical value as a prospective large-scale screening method for fetoplacental function.", "contents": "Rapid assays of urinary estriol in pregnant women. Two devices designed for rapid assay of urinary estriol, the E3 KIT and E3 HAIR KIT, were evaluated using urine samples taken from pregnant women. Additionally, the clinical application of these devices in pregnancy management was examined. Correlations were high between an established method and the E3 KIT method (r = 0.819, p less than 0.001) and between the E3 HAIR KIT method and the E3 KIT method ( r = 0.936, p less than 0.01). E3 HAIR KIT assays showing E3 values of less than 20 microgram/ml (positive at 100-fold dilution of the urine) after the 36th week of pregnancy suggested fetoplacental dysfunction and indicated that more detailed tests were required. The E3 KIT, which provided rapid quantitative assay of urinary estriol, was capable of measuring 10 samples in approximately 3 hours. The E3 HAIR KIT provided semiquantitative assays of 10 samples in 2 hours. The speed, simplicity, and accuracy of the E3 HAIR KIT indicates its high clinical value as a prospective large-scale screening method for fetoplacental function."}
{"id": "PMID:25800", "title": "Total serum cholesterol, triglycerides and phospholipids during the normal menstrual cycle.", "content": "Ten healthy women (mean age, 29 years) with regular menstrual cycles of 26 to 29 days were tested for levels of total serum cholesterol, triglycerides, phospholipids, and estradiol three times during one menstrual cycle-during menstruation, at ovulation, and in the luteal phase. All studies were performed simultaneously. Lipid variations during the menstrual cycle were minimal. Total serum cholesterol, triglycerides, and phospholipids did not correlate with changes in the serum estradiol levels.", "contents": "Total serum cholesterol, triglycerides and phospholipids during the normal menstrual cycle. Ten healthy women (mean age, 29 years) with regular menstrual cycles of 26 to 29 days were tested for levels of total serum cholesterol, triglycerides, phospholipids, and estradiol three times during one menstrual cycle-during menstruation, at ovulation, and in the luteal phase. All studies were performed simultaneously. Lipid variations during the menstrual cycle were minimal. Total serum cholesterol, triglycerides, and phospholipids did not correlate with changes in the serum estradiol levels."}
{"id": "PMID:25801", "title": "Toxoplasma antibodies and spontaneous abortion.", "content": "One hundred and fifty-two women with spontaneous abortion were investigated by hemagglutination (HA) and immunofluorescence antibody (IFA) tests for toxoplasmosis. In 48 cases, quantitive immunoglobulin (Ig) studies and mouse inoculation with gestational material were performed. Positive toxoplasma antibody titers were observed in 62 cases (40.8%) using HA and in 52 cases (38.2%) using IFA. This prevalence was significantly higher than that observed in 80 normal women who served as controls. Toxoplasma gondii was isolated in two cases. No correlation was found between antibody titers and IgG, IgM or IgA levels. We conclude that toxoplasmosis should be considered as the cause of abortion when a patient's antibody titer exceeds 1:256.", "contents": "Toxoplasma antibodies and spontaneous abortion. One hundred and fifty-two women with spontaneous abortion were investigated by hemagglutination (HA) and immunofluorescence antibody (IFA) tests for toxoplasmosis. In 48 cases, quantitive immunoglobulin (Ig) studies and mouse inoculation with gestational material were performed. Positive toxoplasma antibody titers were observed in 62 cases (40.8%) using HA and in 52 cases (38.2%) using IFA. This prevalence was significantly higher than that observed in 80 normal women who served as controls. Toxoplasma gondii was isolated in two cases. No correlation was found between antibody titers and IgG, IgM or IgA levels. We conclude that toxoplasmosis should be considered as the cause of abortion when a patient's antibody titer exceeds 1:256."}
{"id": "PMID:25802", "title": "Training: an integral adjunct to the introduction of newer methods of fertility regulation.", "content": "The provision of new technologies of fertility control that are known to be safer, simpler, and more effective may at first result in higher complication rates, particularly if training in the new techniques is inadequate. This was illustrated by analysis of data on several fertility control methods collected by the International Fertility Research Program. Various studies showed significantly higher complication rates earlier in the series than later, including one study in which complication rates fell dramatically after clinical training was provided. Another study showed the highest complication rate among the physicians performing the fewer number of cases. Finally, one analysis documented greater variability in several clinical criteria among the participating physicians than between the two pieces of equipment being compared. These data document that it is essential to train physicians and other staff members in the proper use of new equipment and techniques if the potential improvements offered by new technologies in fertility regulation are to be realized.", "contents": "Training: an integral adjunct to the introduction of newer methods of fertility regulation. The provision of new technologies of fertility control that are known to be safer, simpler, and more effective may at first result in higher complication rates, particularly if training in the new techniques is inadequate. This was illustrated by analysis of data on several fertility control methods collected by the International Fertility Research Program. Various studies showed significantly higher complication rates earlier in the series than later, including one study in which complication rates fell dramatically after clinical training was provided. Another study showed the highest complication rate among the physicians performing the fewer number of cases. Finally, one analysis documented greater variability in several clinical criteria among the participating physicians than between the two pieces of equipment being compared. These data document that it is essential to train physicians and other staff members in the proper use of new equipment and techniques if the potential improvements offered by new technologies in fertility regulation are to be realized."}
{"id": "PMID:25803", "title": "Laparoscopy for the confirmation and prognostic evaluation of pelvic inflammatory disease.", "content": "A presumptive diagnosis of pelvic inflammatory disease (PID) is usually made in our gynecologic clinics when obscure, acute lower abdominal pain is accompained by fever and abnormal vaginal discharge, urinary and rectal discomfort, marked tenderness of the pelvic organs to palpation, or pelvic masses. In the present study, during a 2-year period, 223 women underwent laparoscopy to confirm this diagnosis. PID was confirmed in 103 (46.2%) of the cases; other serious conditions were diagnosed in 69 (30.9%) of the cases; and no evidence of disease was found in 51 (22.9%) of the cases. The authors conclude that laparoscopy is a valuable tool in the diagnosis of PID.", "contents": "Laparoscopy for the confirmation and prognostic evaluation of pelvic inflammatory disease. A presumptive diagnosis of pelvic inflammatory disease (PID) is usually made in our gynecologic clinics when obscure, acute lower abdominal pain is accompained by fever and abnormal vaginal discharge, urinary and rectal discomfort, marked tenderness of the pelvic organs to palpation, or pelvic masses. In the present study, during a 2-year period, 223 women underwent laparoscopy to confirm this diagnosis. PID was confirmed in 103 (46.2%) of the cases; other serious conditions were diagnosed in 69 (30.9%) of the cases; and no evidence of disease was found in 51 (22.9%) of the cases. The authors conclude that laparoscopy is a valuable tool in the diagnosis of PID."}
{"id": "PMID:25804", "title": "Difficult obstetric vesicovaginal fistula: a report on 12 cases.", "content": "In each of the 12 cases presented, the fistula was the result of obstructed labor. Common features to each case were: (a) a large retropubic defect involving the anterior vaginal wall, bladder and urethra, (b) total or partial urethral rupture, and (c) marked vaginal wall scarring with vaginal stenosis. Primary repair was performed by the vaginal route, and two patients were cured by the first operation. Six patients required two or more vaginal procedures for successful closure. Following repeated failure of vaginal closure, two patients had a successful transvesical closure and two require ureterosigmoidostomy.", "contents": "Difficult obstetric vesicovaginal fistula: a report on 12 cases. In each of the 12 cases presented, the fistula was the result of obstructed labor. Common features to each case were: (a) a large retropubic defect involving the anterior vaginal wall, bladder and urethra, (b) total or partial urethral rupture, and (c) marked vaginal wall scarring with vaginal stenosis. Primary repair was performed by the vaginal route, and two patients were cured by the first operation. Six patients required two or more vaginal procedures for successful closure. Following repeated failure of vaginal closure, two patients had a successful transvesical closure and two require ureterosigmoidostomy."}
{"id": "PMID:25805", "title": "The successful treatment of a case of primary sterility resulting from Fredrickson's Type V hyperlipemia and panhypopituitarism.", "content": "Successful treatment of primary sterility in a woman having the rare association of panhypopituitarism with Fredrickson's Type V hyperlipemia is described. Replacement therapy with l-thyroxine, prednisone and a low fat diet cleared the patient's blood of the excessive chylomicrons and very low density lipoproteins. Ovulation was induced with human gonadotrophins, and triplets (two normal girls and a boy) were born.", "contents": "The successful treatment of a case of primary sterility resulting from Fredrickson's Type V hyperlipemia and panhypopituitarism. Successful treatment of primary sterility in a woman having the rare association of panhypopituitarism with Fredrickson's Type V hyperlipemia is described. Replacement therapy with l-thyroxine, prednisone and a low fat diet cleared the patient's blood of the excessive chylomicrons and very low density lipoproteins. Ovulation was induced with human gonadotrophins, and triplets (two normal girls and a boy) were born."}
{"id": "PMID:25806", "title": "Progesterone metabolism in cultured amniotic fluid cells.", "content": "Amniotic fluid cells obtained by amnicentesis at 16-20 weeks' gestation were grown in culture until a confluent monolayer of cell had been formed. Radiolabeled pregnenolone, progesterone and 20 alpha-dihydroprogesterone were added to the cell cultures; steroid metabolites which formed after 24 and 48 hours of incubation were identified. Incubation of the cell cultures with pregnenolone-3H resulted in the formation of progesterone, 17alpha-progesterone and 20 alpha-dihydroprogesterone. A significant amount of progesterone was identified after incubating the cell cultures with 20 alpha-dihydroprogesterone. The results indicate that 3 beta-ol-dehydrogenase, 17 alpha-hydroxylase and 20 alpha-hydroxysteroid dehydrogenase enzymes are present in cultured amniotic fluid cells obtained at 16-20 weeks' gestation.", "contents": "Progesterone metabolism in cultured amniotic fluid cells. Amniotic fluid cells obtained by amnicentesis at 16-20 weeks' gestation were grown in culture until a confluent monolayer of cell had been formed. Radiolabeled pregnenolone, progesterone and 20 alpha-dihydroprogesterone were added to the cell cultures; steroid metabolites which formed after 24 and 48 hours of incubation were identified. Incubation of the cell cultures with pregnenolone-3H resulted in the formation of progesterone, 17alpha-progesterone and 20 alpha-dihydroprogesterone. A significant amount of progesterone was identified after incubating the cell cultures with 20 alpha-dihydroprogesterone. The results indicate that 3 beta-ol-dehydrogenase, 17 alpha-hydroxylase and 20 alpha-hydroxysteroid dehydrogenase enzymes are present in cultured amniotic fluid cells obtained at 16-20 weeks' gestation."}
{"id": "PMID:25807", "title": "Clostridial sepsis after abortion with PGF2alpha and intracervical laminaria tents--a case report.", "content": "A case of clostridial endomyometritis and sepsis necessitating total abdominal hysterectomy which occurred 12 hours following abortion induced with intraamniotic administration of prostaglandin F2 alpha and laminaria tent insertion is discussed. Cultures from cervical, blood, and surgical specimens all yielded Clostridium perfringens. Intrauterine contamination with this microorganism most likely followed the insertion of laminaria tents through the cervical os, which was colonized with C. perfringens. Since C. perfringens may be present in the microflora of the lower female genital tract, great care must be taken to cleanse this area prior to intracervical laminaria tent insertion.", "contents": "Clostridial sepsis after abortion with PGF2alpha and intracervical laminaria tents--a case report. A case of clostridial endomyometritis and sepsis necessitating total abdominal hysterectomy which occurred 12 hours following abortion induced with intraamniotic administration of prostaglandin F2 alpha and laminaria tent insertion is discussed. Cultures from cervical, blood, and surgical specimens all yielded Clostridium perfringens. Intrauterine contamination with this microorganism most likely followed the insertion of laminaria tents through the cervical os, which was colonized with C. perfringens. Since C. perfringens may be present in the microflora of the lower female genital tract, great care must be taken to cleanse this area prior to intracervical laminaria tent insertion."}
{"id": "PMID:25808", "title": "Experience with minilaparotomy in the Philippines.", "content": "This paper presents the socio-demographic characteristics, medical histories, and clinical data on 651 women sterilized by interval minilaparotomy procedures in Manila, Philippines. About two thirds of the procedures were performed with local anesthesia; the Pomeroy technique was used for tubal ligation. In 2.8% of the patients, salpingectomy or fimbriectomy was performed on one side because of surgical difficulties and complications. Surgical difficulties were encountered in 19.8% of the procedures; adhesions (4.3%) and bowel interference (4.0%) were the most frequent causes of surgical difficulty. Complications occurred during surgery in 1.7% of the procedures. Early postoperative complications were noted in 9.1% of the cases. None of the patients required readmission to the hospital. While 612 women were followed up at 6 months, 299 were followed up at 12 months. One women (0.2%) became pregnant after sterilization; at repeat minilaparotomy, ligation of the left round ligament rather than the tube was observed. Pelvic surgery, other than pregnancy-related surgery, during the year following sterilization was reported for one patient who underwent exploratory laparotomy with appendectomy and oophorocystectomy. Menstrual pattern changes were minimal. The results of this study suggest that tubal ligation via minilaparotomy is practical, safe, and effective.", "contents": "Experience with minilaparotomy in the Philippines. This paper presents the socio-demographic characteristics, medical histories, and clinical data on 651 women sterilized by interval minilaparotomy procedures in Manila, Philippines. About two thirds of the procedures were performed with local anesthesia; the Pomeroy technique was used for tubal ligation. In 2.8% of the patients, salpingectomy or fimbriectomy was performed on one side because of surgical difficulties and complications. Surgical difficulties were encountered in 19.8% of the procedures; adhesions (4.3%) and bowel interference (4.0%) were the most frequent causes of surgical difficulty. Complications occurred during surgery in 1.7% of the procedures. Early postoperative complications were noted in 9.1% of the cases. None of the patients required readmission to the hospital. While 612 women were followed up at 6 months, 299 were followed up at 12 months. One women (0.2%) became pregnant after sterilization; at repeat minilaparotomy, ligation of the left round ligament rather than the tube was observed. Pelvic surgery, other than pregnancy-related surgery, during the year following sterilization was reported for one patient who underwent exploratory laparotomy with appendectomy and oophorocystectomy. Menstrual pattern changes were minimal. The results of this study suggest that tubal ligation via minilaparotomy is practical, safe, and effective."}
{"id": "PMID:25810", "title": "The potential reduction of medical complications from induced abortion.", "content": "Reducing medical complications resulting from induced abortion by identifying the safest and most appropriate procedures(s) for each gestational age is the purpose of this study. Data on all women who had induced abortions at all hospitals in the State of Hawaii where such procedures were performed between March 11, 1970, when the new abortion law went into effect, and June 30, 1974 were analyzed. Study findings show that if the abortion procedure with the least risk of complications at each length of gestation were selected a reduction in the complication rate of nearly 30% could result.", "contents": "The potential reduction of medical complications from induced abortion. Reducing medical complications resulting from induced abortion by identifying the safest and most appropriate procedures(s) for each gestational age is the purpose of this study. Data on all women who had induced abortions at all hospitals in the State of Hawaii where such procedures were performed between March 11, 1970, when the new abortion law went into effect, and June 30, 1974 were analyzed. Study findings show that if the abortion procedure with the least risk of complications at each length of gestation were selected a reduction in the complication rate of nearly 30% could result."}
{"id": "PMID:25811", "title": "Some demographic aspects of pregnancy histories of sterilized women in the Mission Hospitals of Karnataka.", "content": "This study deals with the pregnancy histories of 534 women whow were sterilized in the Mission Hospitals in Karnataka State (India) during 1974 and 1975. Fertility differentials prevailing in various sociocultural groups are indicated. The study highlights the prevalence of adolescent sterility and also emphasizes the need for spacing pregnancies to avoid fetal wastage. The differentials in the sex ratio at each birth order are described. the need for further investigation in this field of demography is emphasized.", "contents": "Some demographic aspects of pregnancy histories of sterilized women in the Mission Hospitals of Karnataka. This study deals with the pregnancy histories of 534 women whow were sterilized in the Mission Hospitals in Karnataka State (India) during 1974 and 1975. Fertility differentials prevailing in various sociocultural groups are indicated. The study highlights the prevalence of adolescent sterility and also emphasizes the need for spacing pregnancies to avoid fetal wastage. The differentials in the sex ratio at each birth order are described. the need for further investigation in this field of demography is emphasized."}
{"id": "PMID:25813", "title": "A new modification of colpocleisis for treatment of total procidentia in old age.", "content": "A new approach for treating uterine prolapse in old age is presented. Fiftten patients underwent this operation during our 5-year study. The procedure is simple and brief and can be performed, using a local anesthetic, on patients whose general condition is poor. The patients in our series had no immediate postoperative complications, and those who attended our follow-up clinic had no recurrence of the disease.", "contents": "A new modification of colpocleisis for treatment of total procidentia in old age. A new approach for treating uterine prolapse in old age is presented. Fiftten patients underwent this operation during our 5-year study. The procedure is simple and brief and can be performed, using a local anesthetic, on patients whose general condition is poor. The patients in our series had no immediate postoperative complications, and those who attended our follow-up clinic had no recurrence of the disease."}
{"id": "PMID:25814", "title": "Study of \"spontaneous\" abortion in Thailand.", "content": "This analysis includes data on 3 530 patients with septic or incomplete, inevitable or threatened abortions who were treated at the Siriraj Hospital in Bangkok between January 1972 and December 1973. Data on the patients' socio-demographic characteristics; their reproductive, abortion, and medical histories; their pre- and postabortion contraceptive acceptance; and a clinical profile of their abortion treatment, including procedure time, length of hospitalization, and immediate and delayed postoperative complications are analyzed.", "contents": "Study of \"spontaneous\" abortion in Thailand. This analysis includes data on 3 530 patients with septic or incomplete, inevitable or threatened abortions who were treated at the Siriraj Hospital in Bangkok between January 1972 and December 1973. Data on the patients' socio-demographic characteristics; their reproductive, abortion, and medical histories; their pre- and postabortion contraceptive acceptance; and a clinical profile of their abortion treatment, including procedure time, length of hospitalization, and immediate and delayed postoperative complications are analyzed."}
{"id": "PMID:25815", "title": "The cold sterilization of abortion cannulae.", "content": "The purpose of this study was to determine if cold sterilization is a feasible method for sterilizing abortion cannulae and, if so, to find the appropriate solutions and time intervals for this sterilization process. Study findings show that abortion cannulae can be cold sterilized by soaking them for a minimum of 10 minutes in a solution of Cidex or 95% ethanol. Soaking the cannulae for 20 minutes in a 2% tincture of iodine solution also appears to be useful for decontamination purposes.", "contents": "The cold sterilization of abortion cannulae. The purpose of this study was to determine if cold sterilization is a feasible method for sterilizing abortion cannulae and, if so, to find the appropriate solutions and time intervals for this sterilization process. Study findings show that abortion cannulae can be cold sterilized by soaking them for a minimum of 10 minutes in a solution of Cidex or 95% ethanol. Soaking the cannulae for 20 minutes in a 2% tincture of iodine solution also appears to be useful for decontamination purposes."}
{"id": "PMID:25816", "title": "Extramembranous pregnancy: a case report.", "content": "A rare case of extramembranous pregnancy is reported. It was associated with intermittent loss of liquor and bloody discharge beginning at about the 25th week of gestation. An anencephalic infant was delivered alive from a breech presentation during the 31st week of gestation. The placenta was markedly circumvallate, with short, thick membranes which did not cover more than 10% of the infant. The course of the pregnancy and the examination of the infant and placenta are discussed, and the pertinent literature is reviewed.", "contents": "Extramembranous pregnancy: a case report. A rare case of extramembranous pregnancy is reported. It was associated with intermittent loss of liquor and bloody discharge beginning at about the 25th week of gestation. An anencephalic infant was delivered alive from a breech presentation during the 31st week of gestation. The placenta was markedly circumvallate, with short, thick membranes which did not cover more than 10% of the infant. The course of the pregnancy and the examination of the infant and placenta are discussed, and the pertinent literature is reviewed."}
{"id": "PMID:25820", "title": "Management of acute anxiety syndrome with parenterally administered lorazepam.", "content": "After the preliminary successful use of injectable lorazepam in calming 20 patients who presented with acute anxiety crises, a formal study of 115 other such patients was carried out. All were seen either in a hospital emergency room or on an emergency out-patient basis in private practice. Treatment consisted of an initial intravenous injection of lorazepam (3mg) followed, if necessary, by up to three further injections within a 24-hour period. The result was usually dramatic: complete abolition or reasonable control of symptoms within 30 minutes in all but 2 patients. The major effect was relaxant and sedative; 62 patients slept following the injections. although 55 could be easily aroused, 7 could not. Of the other patients, 49 remained awake but relaxed; only 4 remained tense and were regarded as treatment failures. No significant side-effects or changes in vital signs were noted. The results support and extend those reported by other invesigators in a recent controlled, double-blind (but otherwise similarly conducted) trial.", "contents": "Management of acute anxiety syndrome with parenterally administered lorazepam. After the preliminary successful use of injectable lorazepam in calming 20 patients who presented with acute anxiety crises, a formal study of 115 other such patients was carried out. All were seen either in a hospital emergency room or on an emergency out-patient basis in private practice. Treatment consisted of an initial intravenous injection of lorazepam (3mg) followed, if necessary, by up to three further injections within a 24-hour period. The result was usually dramatic: complete abolition or reasonable control of symptoms within 30 minutes in all but 2 patients. The major effect was relaxant and sedative; 62 patients slept following the injections. although 55 could be easily aroused, 7 could not. Of the other patients, 49 remained awake but relaxed; only 4 remained tense and were regarded as treatment failures. No significant side-effects or changes in vital signs were noted. The results support and extend those reported by other invesigators in a recent controlled, double-blind (but otherwise similarly conducted) trial."}
{"id": "PMID:25824", "title": "[Pregnancy and labor in twins. II. Determination of twin pregnancy and avoidance of premature birth (author's transl)].", "content": "In about 65% of the 258 twin births which occurred at the University Gynaecological Hospital, Z\u00fcrich, from 1966 to 1976, it was possible to diagnose the twin pregnancy before the birth of the first twin. Twin pregnancy could be diagnosed in 96.2% of all the cases before the birth of the first twin, after routine ultrasound diagnosis of pregnancy had been introduced. Prerequisite of optimal treatment of pregnancy is a very early diagnosis which is only possible by widest use of ultrasound investigation technique. The rate of premature births was reduced from 48.0% to 27.3% by means of complete rest in bed and prophylactic tocolysis with a betamimetic from the 32nd to the 37th week of pregnancy. At the same time, the number of underweight children below 2.500 g was reduced by means of this treatment from 60.1% to 34.1%. It seems to be an undisputable fact that prolonged hospitalization in the last three months of pregnancy will improve the prognosis.", "contents": "[Pregnancy and labor in twins. II. Determination of twin pregnancy and avoidance of premature birth (author's transl)]. In about 65% of the 258 twin births which occurred at the University Gynaecological Hospital, Z\u00fcrich, from 1966 to 1976, it was possible to diagnose the twin pregnancy before the birth of the first twin. Twin pregnancy could be diagnosed in 96.2% of all the cases before the birth of the first twin, after routine ultrasound diagnosis of pregnancy had been introduced. Prerequisite of optimal treatment of pregnancy is a very early diagnosis which is only possible by widest use of ultrasound investigation technique. The rate of premature births was reduced from 48.0% to 27.3% by means of complete rest in bed and prophylactic tocolysis with a betamimetic from the 32nd to the 37th week of pregnancy. At the same time, the number of underweight children below 2.500 g was reduced by means of this treatment from 60.1% to 34.1%. It seems to be an undisputable fact that prolonged hospitalization in the last three months of pregnancy will improve the prognosis."}
{"id": "PMID:25825", "title": "[Study of H-2 mutations in mice. VII. The defectiveness of the H-2ba mutant in the hemagglutination and graft vs host reactions].", "content": "Three mutants of the H-2K gene within the mouse major histocompatibility complex were studied. Antisera anti-H-2.5 + 39 were unable to agglutinate H-2ba and H-2bf mutant red blood cells. The same sera moderately agglutinated H-2b red blood cells. The H-2ba red blood cells did not absorb in vitro the activity from an anti-H-2.5 serum, while the H-2b cells did. Thus, these results indicate the existence of qualitative SD antigenic differences among H-2Kb derived mutants. In the proliferative graft versus host test the H-2ba spleen cells did not induce spleen enlargement in the H-2bd recipients, while pronounced reaction was recovered in bd-ba combination. The (baXb) F1 hybrid cells were as efficient as b/b homozygous cells. The data suggest that the H-2K gene product may be involved in the antigen recognition process by T cells.", "contents": "[Study of H-2 mutations in mice. VII. The defectiveness of the H-2ba mutant in the hemagglutination and graft vs host reactions]. Three mutants of the H-2K gene within the mouse major histocompatibility complex were studied. Antisera anti-H-2.5 + 39 were unable to agglutinate H-2ba and H-2bf mutant red blood cells. The same sera moderately agglutinated H-2b red blood cells. The H-2ba red blood cells did not absorb in vitro the activity from an anti-H-2.5 serum, while the H-2b cells did. Thus, these results indicate the existence of qualitative SD antigenic differences among H-2Kb derived mutants. In the proliferative graft versus host test the H-2ba spleen cells did not induce spleen enlargement in the H-2bd recipients, while pronounced reaction was recovered in bd-ba combination. The (baXb) F1 hybrid cells were as efficient as b/b homozygous cells. The data suggest that the H-2K gene product may be involved in the antigen recognition process by T cells."}
{"id": "PMID:25826", "title": "Vitamin D-3 intestinal absorption in vivo: influence of fatty acids, bile salts, and perfusate pH on absorption.", "content": "Intestinal absorption of vitamin D-3 in physiological concentrations was studied in the live unanesthetised rat. In both the jejunum and the ileum a linear relationship was found between the absorption rate of the vitamin and its intraluminal concentration. Increasing the sodium taurocholate concentation in the perfusate above 5mM did not change ileal absorption rate but did decrease jejunal absorption rate. The vitamin's rate of absorption was raised by increases in either the hydrogen ion concentration in vivo is mediated by passive diffusion. The rate of absorption of ttion or the perfusate's flow rate. Addition of 2.5 mM fatty acids of varying chain length and degrees of saturation resulted in a decrease in the rate of vitamin D-3 absorption. These experiments indicate that vitamin D-3 absorption in vivo is mediated by passive diffusion. The rate of absorption of the vitamin is influenced by the composition of the perfusate and the thickness of the unstirred layer.", "contents": "Vitamin D-3 intestinal absorption in vivo: influence of fatty acids, bile salts, and perfusate pH on absorption. Intestinal absorption of vitamin D-3 in physiological concentrations was studied in the live unanesthetised rat. In both the jejunum and the ileum a linear relationship was found between the absorption rate of the vitamin and its intraluminal concentration. Increasing the sodium taurocholate concentation in the perfusate above 5mM did not change ileal absorption rate but did decrease jejunal absorption rate. The vitamin's rate of absorption was raised by increases in either the hydrogen ion concentration in vivo is mediated by passive diffusion. The rate of absorption of ttion or the perfusate's flow rate. Addition of 2.5 mM fatty acids of varying chain length and degrees of saturation resulted in a decrease in the rate of vitamin D-3 absorption. These experiments indicate that vitamin D-3 absorption in vivo is mediated by passive diffusion. The rate of absorption of the vitamin is influenced by the composition of the perfusate and the thickness of the unstirred layer."}
{"id": "PMID:25827", "title": "Effects of a protein meal, intraduodenal HCl, and oleic acid on portal and peripheral venous secretin and on pancreatic bicarbonate secretion.", "content": "We have studied the effect of a protein meal on secretin (IRS) concentration in dogs and humans using a radioimmunoassay of improved sensitivity (8 pg/ml). After a meal, pancreatic bicarbonate secretion (PBS) increased markedly and proximal duodenal pH decreased from 6.2 to 4.3. Portal and peripheral IRS concentrations, however, remained unchanged in eight dogs and five patients with cirrhosis of the liver. Similarly, an alkaline solution of sodium oleate (pH 9.2) stimulated PBS but not IRS. Intraduodenal administration of various amounts of HCl in dogs demonstrated that acid-stimulated PBS was invariably accompanied by rises in peripheral venous IRS concentration. We conclude that the postprandial stimulation of PBS involves mechanisms more complex than acid-stimulated secretin release.", "contents": "Effects of a protein meal, intraduodenal HCl, and oleic acid on portal and peripheral venous secretin and on pancreatic bicarbonate secretion. We have studied the effect of a protein meal on secretin (IRS) concentration in dogs and humans using a radioimmunoassay of improved sensitivity (8 pg/ml). After a meal, pancreatic bicarbonate secretion (PBS) increased markedly and proximal duodenal pH decreased from 6.2 to 4.3. Portal and peripheral IRS concentrations, however, remained unchanged in eight dogs and five patients with cirrhosis of the liver. Similarly, an alkaline solution of sodium oleate (pH 9.2) stimulated PBS but not IRS. Intraduodenal administration of various amounts of HCl in dogs demonstrated that acid-stimulated PBS was invariably accompanied by rises in peripheral venous IRS concentration. We conclude that the postprandial stimulation of PBS involves mechanisms more complex than acid-stimulated secretin release."}
{"id": "PMID:25828", "title": "Pathophysiological responses to meals in the Zollinger-Ellison syndrome: I. Paradoxical postprandial inhibition of gastric secretion.", "content": "The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia.", "contents": "Pathophysiological responses to meals in the Zollinger-Ellison syndrome: I. Paradoxical postprandial inhibition of gastric secretion. The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia."}
{"id": "PMID:25829", "title": "Intestinal phase of gastric secretion in patients with duodenal ulcer.", "content": "In 10 healthy subjects and 10 duodenal ulcer patients the intestinal phase of gastric acid secretion was studied by intraduodenal infusion of a 10% liver extract meal (pH 7) at 400 ml/h for three hours. A gastroduodenal double lumen tube with two balloons was used to block the pylorus and to prevent duodenogastric reflux. Gastric acid response to a duodenal meal of liver extract reached a peak at the end of the first hour of infusion of the extract and was then followed by a relatively well-sustained plateau. When the figure was normalised as a percentage of peak response to pentagastrin it was about 45% in healthy subjects and 63% in duodenal ulcer patients. Serum gastrin concentration increased significantly during a duodenal meal of liver extract only in duodenal ulcer patients and not in healthy subjects. The combination of the duodenal meal of liver extract with pentagastrin infusion resulted in a significantly greater increase in acid output in duodenal ulcer patients than in healthy controls. Duodenal perfusion with a liver extract meal in which the pH was gradually decreased caused a pH-dependent reduction in acid output, but not in serum gastrin, both in the duodenal ulcer patients and in healthy subjects. This study shows that the intestinal phase in man results in a potent gastric acid stimulation which is pH-dependent, greatly augmented by pentagastrin, and more vigorous in duodenal ulcer patients than in healthy controls.", "contents": "Intestinal phase of gastric secretion in patients with duodenal ulcer. In 10 healthy subjects and 10 duodenal ulcer patients the intestinal phase of gastric acid secretion was studied by intraduodenal infusion of a 10% liver extract meal (pH 7) at 400 ml/h for three hours. A gastroduodenal double lumen tube with two balloons was used to block the pylorus and to prevent duodenogastric reflux. Gastric acid response to a duodenal meal of liver extract reached a peak at the end of the first hour of infusion of the extract and was then followed by a relatively well-sustained plateau. When the figure was normalised as a percentage of peak response to pentagastrin it was about 45% in healthy subjects and 63% in duodenal ulcer patients. Serum gastrin concentration increased significantly during a duodenal meal of liver extract only in duodenal ulcer patients and not in healthy subjects. The combination of the duodenal meal of liver extract with pentagastrin infusion resulted in a significantly greater increase in acid output in duodenal ulcer patients than in healthy controls. Duodenal perfusion with a liver extract meal in which the pH was gradually decreased caused a pH-dependent reduction in acid output, but not in serum gastrin, both in the duodenal ulcer patients and in healthy subjects. This study shows that the intestinal phase in man results in a potent gastric acid stimulation which is pH-dependent, greatly augmented by pentagastrin, and more vigorous in duodenal ulcer patients than in healthy controls."}
{"id": "PMID:25830", "title": "Induction of gastro-oesophageal reflux by alcohol.", "content": "In order to establish whether alcohol in amounts in amounts customarily imbibed during social drinking causes gastro-oesophageal reflux, 12 healthy young individuals, without symptoms of gastro-oesophageal reflux, were studied twice. Each time, distal oesophageal pH was monitored continuously for three hours after a standard meal which included either 180 ml 100 proof vodka or 180 ml water. The order of studies with and without alcohol was random. Peak blood alcohol concentrations ranged between 0.63 and 1.29 g/l. Eleven of the 12 subjects refluxed more after alcohol; and the difference in mean reflux scores for studies with and without alcohol was highly significant. We conclude that relatively modest quanttities of alcohol induce gastro-oesophageal reflux in healthy people.", "contents": "Induction of gastro-oesophageal reflux by alcohol. In order to establish whether alcohol in amounts in amounts customarily imbibed during social drinking causes gastro-oesophageal reflux, 12 healthy young individuals, without symptoms of gastro-oesophageal reflux, were studied twice. Each time, distal oesophageal pH was monitored continuously for three hours after a standard meal which included either 180 ml 100 proof vodka or 180 ml water. The order of studies with and without alcohol was random. Peak blood alcohol concentrations ranged between 0.63 and 1.29 g/l. Eleven of the 12 subjects refluxed more after alcohol; and the difference in mean reflux scores for studies with and without alcohol was highly significant. We conclude that relatively modest quanttities of alcohol induce gastro-oesophageal reflux in healthy people."}
{"id": "PMID:25831", "title": "24-hour rhythms in uterine and umbilical blood flows of conscious pregnant sheep.", "content": "The possibility that 24-hour rhythms exist in uterine blood flow (UtBF) and umbilical blood (UmBF) was investigated in 5 days postoperative chronically instrumented near-term pregnant sheep acclimated to a controlled environment. UtBF, UmBF and pressure measurements were made at 15-min intervals over 24 h beginning at 0800 h. Each data series was examined for the presence of significant rhythms of a 24-hour period using a method of Fourier analysis. UtBF 24-hour rhythms were found in all ewes; UmBF 24-hour rhythms were found in 4 of 5 lambs. A consistent reciprocal phase relationship between UtBF and UmBF was evident within animals. There were no associated rhythms in maternal arterial, fetal arterial, or amniotic fluid pressures. These results indicate that the presence of circadian rhythms must be considered as a possible variable when long-term uteroplacental hemodynamic studies are planned.", "contents": "24-hour rhythms in uterine and umbilical blood flows of conscious pregnant sheep. The possibility that 24-hour rhythms exist in uterine blood flow (UtBF) and umbilical blood (UmBF) was investigated in 5 days postoperative chronically instrumented near-term pregnant sheep acclimated to a controlled environment. UtBF, UmBF and pressure measurements were made at 15-min intervals over 24 h beginning at 0800 h. Each data series was examined for the presence of significant rhythms of a 24-hour period using a method of Fourier analysis. UtBF 24-hour rhythms were found in all ewes; UmBF 24-hour rhythms were found in 4 of 5 lambs. A consistent reciprocal phase relationship between UtBF and UmBF was evident within animals. There were no associated rhythms in maternal arterial, fetal arterial, or amniotic fluid pressures. These results indicate that the presence of circadian rhythms must be considered as a possible variable when long-term uteroplacental hemodynamic studies are planned."}
{"id": "PMID:25832", "title": "[The hypertensive effect of adyston and etilefrin. Comparative animal experimental studies].", "content": "According to the results obtained under the described conditions it can be stated that after i.v. administration Adyston induces a dose-dependent rise in systolic and diastolic blood pressure, in comparison with etilefrin the new product Adyston shows a greater potency in rising the systolic and diastolic blood pressure; Adyston induced rise of blood pressure is in general of longer duration in comparison with that induced by etilefrin, it is interesting that in the dose of 0.01 mg/kg Adyston increases the arterial blood pressure but at the same time slightly decreases the heart rate; this is not the case after administration of etilefrin which at the same dose increases both arterial blood pressure and heart rate.", "contents": "[The hypertensive effect of adyston and etilefrin. Comparative animal experimental studies]. According to the results obtained under the described conditions it can be stated that after i.v. administration Adyston induces a dose-dependent rise in systolic and diastolic blood pressure, in comparison with etilefrin the new product Adyston shows a greater potency in rising the systolic and diastolic blood pressure; Adyston induced rise of blood pressure is in general of longer duration in comparison with that induced by etilefrin, it is interesting that in the dose of 0.01 mg/kg Adyston increases the arterial blood pressure but at the same time slightly decreases the heart rate; this is not the case after administration of etilefrin which at the same dose increases both arterial blood pressure and heart rate."}
{"id": "PMID:25833", "title": "[Treatment of parkinson's syndrome. New developments].", "content": "The treatment of Parkinson's syndrome with newly developed drugs has to be planned within the entire therapeutic concept. Besides the anticholinergics, levodopa, amantadines and beta-blockers should be taken into consideration. When necessary, hypnotics, ataractics and antidepressant drugs should be applied.", "contents": "[Treatment of parkinson's syndrome. New developments]. The treatment of Parkinson's syndrome with newly developed drugs has to be planned within the entire therapeutic concept. Besides the anticholinergics, levodopa, amantadines and beta-blockers should be taken into consideration. When necessary, hypnotics, ataractics and antidepressant drugs should be applied."}
{"id": "PMID:25834", "title": "Insulin effect on proteolytic activities in rat skeletal muscle.", "content": "Proteolytic activity has been measure in rat skeletal muscle by use of [14C]-hemoglobin as substrate. The activity of the alkaline proteinases increases during starvation and in diabetic state. In streptozotocin-diabetic animals the activity of alkaline proteases increases to 300% over a time of 21 days. Insulin treatment reverses the enhanced enzyme activity to normal level.", "contents": "Insulin effect on proteolytic activities in rat skeletal muscle. Proteolytic activity has been measure in rat skeletal muscle by use of [14C]-hemoglobin as substrate. The activity of the alkaline proteinases increases during starvation and in diabetic state. In streptozotocin-diabetic animals the activity of alkaline proteases increases to 300% over a time of 21 days. Insulin treatment reverses the enhanced enzyme activity to normal level."}
{"id": "PMID:25835", "title": "The effect of stress or glucose feeding on hepatic tyrosine aminotransferase activity and liver and plasma tyrosine level of intact and adrenalectomized rats.", "content": "The increase of hepatic tyrosine aminotransferase and the fall of plasma tyrosine in rats subjected to immobilization is reconfirmed. Moreover, the same effects three hrs after exposuing the animals to 400 revolutions in Noble-Collip drums are described. However, in bilaterally adrenalectomized rats both hepatic tyrosine aminotransferase and plasma tyrosine remain unchanged after injury and the liver tyrosine level increase. Finally, in animals fed overnight exclusively with 15% glucose solution the well-known decrease of hepatic tyrosine aminotransferase was found paralleled by increased plasma tyrosine levels. A regulatory role of tyrosine aminotransferase in establishing the level of tyrosine in plasma is suggested.", "contents": "The effect of stress or glucose feeding on hepatic tyrosine aminotransferase activity and liver and plasma tyrosine level of intact and adrenalectomized rats. The increase of hepatic tyrosine aminotransferase and the fall of plasma tyrosine in rats subjected to immobilization is reconfirmed. Moreover, the same effects three hrs after exposuing the animals to 400 revolutions in Noble-Collip drums are described. However, in bilaterally adrenalectomized rats both hepatic tyrosine aminotransferase and plasma tyrosine remain unchanged after injury and the liver tyrosine level increase. Finally, in animals fed overnight exclusively with 15% glucose solution the well-known decrease of hepatic tyrosine aminotransferase was found paralleled by increased plasma tyrosine levels. A regulatory role of tyrosine aminotransferase in establishing the level of tyrosine in plasma is suggested."}
{"id": "PMID:25836", "title": "Liver cell heterogeneity. The distribution of fructose-bisphosphatase in fed and fasted rats and in man.", "content": "Periportal and perivenous hepatocytes were isolated by microdissection from lyophilized liver slices (16 micrometer) from fed and fasted rats and from a human patient. NADP/NADPH cycling was used to determine fructose-1,6-bisphosphatase activity in the isolated hepatocytes (10 ng dry weight). The periportal hepatocytes contain 3 times as much fructose-1,6-bisphosphatase activity as the perivenous hepatocytes. A 24 h fast led to two-fold increase in the activity in the periportal hepatocytes and a four-fold increase in the perivenous hepatocytes. Fructose-1,6-bisphosphatase parallels closely with the key enzyme phosphoenolpyruvate carboxykinase, and therefore can be considered a suitable marker for gluconeogenic capacity.", "contents": "Liver cell heterogeneity. The distribution of fructose-bisphosphatase in fed and fasted rats and in man. Periportal and perivenous hepatocytes were isolated by microdissection from lyophilized liver slices (16 micrometer) from fed and fasted rats and from a human patient. NADP/NADPH cycling was used to determine fructose-1,6-bisphosphatase activity in the isolated hepatocytes (10 ng dry weight). The periportal hepatocytes contain 3 times as much fructose-1,6-bisphosphatase activity as the perivenous hepatocytes. A 24 h fast led to two-fold increase in the activity in the periportal hepatocytes and a four-fold increase in the perivenous hepatocytes. Fructose-1,6-bisphosphatase parallels closely with the key enzyme phosphoenolpyruvate carboxykinase, and therefore can be considered a suitable marker for gluconeogenic capacity."}
{"id": "PMID:25837", "title": "Purification and characterization of aromatic-amino-acid-glyoxylate aminotransferase from monkey and rat liver.", "content": "Aromatic-amino-acid-glyoxylate aminotransferase was highly purified from the mitochondrial fraction of livers from monkey and glucagon-injected rats. The two enzyme preparations showed physical and enzymic properties different from a kynurenine aminotransferase previously described. The two enzymes had nearly identical molecular weights (approximate 80 000), isoelectric points (pH 8.0) and pH optima (pH 8.0 - 8.5). However, a difference in substrate specificity was observed between the two enzymes. Both enzymes utilized glyoxylate, pyruvate, hydroxypyruvate and 2-oxo-4-methyl-thiobutyrate as effective amino acceptors. 2-Oxoglutarate was active for rat enzyme but not for monkey enzyme. With glyoxylate, amino donors were effective in the following order of activity; phenylalanine greater than histidine greater than tyrosine greater than tryptophan greater than 5-hydroxytrypotphan greater than kynurenine for the rat enzyme, and phenylalanine greater than kynurenine greater than histidine greater than tryptophan greater than 5-hydroxy-tryptophan for the monkey enzyme.", "contents": "Purification and characterization of aromatic-amino-acid-glyoxylate aminotransferase from monkey and rat liver. Aromatic-amino-acid-glyoxylate aminotransferase was highly purified from the mitochondrial fraction of livers from monkey and glucagon-injected rats. The two enzyme preparations showed physical and enzymic properties different from a kynurenine aminotransferase previously described. The two enzymes had nearly identical molecular weights (approximate 80 000), isoelectric points (pH 8.0) and pH optima (pH 8.0 - 8.5). However, a difference in substrate specificity was observed between the two enzymes. Both enzymes utilized glyoxylate, pyruvate, hydroxypyruvate and 2-oxo-4-methyl-thiobutyrate as effective amino acceptors. 2-Oxoglutarate was active for rat enzyme but not for monkey enzyme. With glyoxylate, amino donors were effective in the following order of activity; phenylalanine greater than histidine greater than tyrosine greater than tryptophan greater than 5-hydroxytrypotphan greater than kynurenine for the rat enzyme, and phenylalanine greater than kynurenine greater than histidine greater than tryptophan greater than 5-hydroxy-tryptophan for the monkey enzyme."}
{"id": "PMID:25838", "title": "Studies on the involvement of lysosomes in estrogen action, I. Isolation and enzymatic properties of pig endometrial lysosomes.", "content": "Pig endometrium cells, collected by curettage and homogenized in an all-glass Potter Elvehjem homogenizer, gave a considerably higher yield of intact mitochondria and lysosomes than homogenates of whole uterus obtained with the Ultraturrax or the Parr bomb. After homogenization of the cells and subfractionation in the presence of Mg2, mitochondria and lysosomes equilibrated at the same modal density in isopycnic centrifugation. Homogenization and subfractionation in buffers devoid of divalent cations and containing EDTA resulted in a decrease in the buoyant density of mitochondria, allowing for a separation from lysosomes. The pH optima and the specific activities of two mitochondrial enzymes and eight hydrolyases used as marker enzymes were determined. The morphological characteristics of fractions were established by electron microscopy. Preliminary results indicate an involvement of lysosomes in steroid metabolism rather than in steroid and receptor translocation into the nucleus.", "contents": "Studies on the involvement of lysosomes in estrogen action, I. Isolation and enzymatic properties of pig endometrial lysosomes. Pig endometrium cells, collected by curettage and homogenized in an all-glass Potter Elvehjem homogenizer, gave a considerably higher yield of intact mitochondria and lysosomes than homogenates of whole uterus obtained with the Ultraturrax or the Parr bomb. After homogenization of the cells and subfractionation in the presence of Mg2, mitochondria and lysosomes equilibrated at the same modal density in isopycnic centrifugation. Homogenization and subfractionation in buffers devoid of divalent cations and containing EDTA resulted in a decrease in the buoyant density of mitochondria, allowing for a separation from lysosomes. The pH optima and the specific activities of two mitochondrial enzymes and eight hydrolyases used as marker enzymes were determined. The morphological characteristics of fractions were established by electron microscopy. Preliminary results indicate an involvement of lysosomes in steroid metabolism rather than in steroid and receptor translocation into the nucleus."}
{"id": "PMID:25845", "title": "Bacteriological findings in the transtracheal aspirate from patients with acute exacerbation of chronic bronchitis.", "content": "Transtracheal aspirates from 87 patients with acute exacerbations of chronic bronchitis who had received no recent antibiotic treatment were examined. A single bacterial species was found in 83% of positive cultures. Predominant pathogens were Haemophilus influenzae and Streptococcus pneumoniae which occurred jointly or separately in 50% of positive cultures. Bacteria traditionally considered as non-pathogenic for the lower respiratory tract also appeared to play an aetiological role. Enterobacteriaceae and anaerobes were infrequent. No bacterial growth was found in 11 cases.", "contents": "Bacteriological findings in the transtracheal aspirate from patients with acute exacerbation of chronic bronchitis. Transtracheal aspirates from 87 patients with acute exacerbations of chronic bronchitis who had received no recent antibiotic treatment were examined. A single bacterial species was found in 83% of positive cultures. Predominant pathogens were Haemophilus influenzae and Streptococcus pneumoniae which occurred jointly or separately in 50% of positive cultures. Bacteria traditionally considered as non-pathogenic for the lower respiratory tract also appeared to play an aetiological role. Enterobacteriaceae and anaerobes were infrequent. No bacterial growth was found in 11 cases."}
{"id": "PMID:25847", "title": "Antihypertensive effect of trimepranol, a new beta-blocking agent.", "content": "Trimepranol (TMP) is a new propranolol-like, non-selective beta-adrenoreceptor blocking drug. Its antihypertensive effect versus placebo was evaluated in a double-blind corss-over study in 25 ambulatory patients, whose supine diastolic blood pressure (BP) was at least 95 mm Hg. After four weeks treatment with placebo, the dose of TMP was titrated weekly until the supine diastolic BP was below 95 mm Hg or intolerable side effects occurred. The trimepranol dose thus determined was 10 mg bid for three patients, 20 mg bid for twelve patients and 40 mg bid for ten patients. The subsequent double-blind cross-over study consisted of two six weeks treatment periods, either with trimepranol followed by placebo (Group I) or in reverse order (Group II). BP and heart rate at the end of these periods were compared. Supine BP fell from 156 +/- 3/105 +/- 2 mm Hg at the end of placebo periods to 140 +/- 2/93 +/- 1 mm Hg (p less than 0.001) for systolic and diastolic BP at the end of trimepranol periods, when the data of Groups I and II are pooled. In 19 out of 25 patients, supine diastolic BP declined below 95 mmHg during the trimepranol period. A statistically significant correlation was found between the antihypertensive and bradycardic effects of trimepranol. Mild side effects occurred in the heart volumes of the patients. We conclude that bid trimepranol is an effective antihypertensive agent.", "contents": "Antihypertensive effect of trimepranol, a new beta-blocking agent. Trimepranol (TMP) is a new propranolol-like, non-selective beta-adrenoreceptor blocking drug. Its antihypertensive effect versus placebo was evaluated in a double-blind corss-over study in 25 ambulatory patients, whose supine diastolic blood pressure (BP) was at least 95 mm Hg. After four weeks treatment with placebo, the dose of TMP was titrated weekly until the supine diastolic BP was below 95 mm Hg or intolerable side effects occurred. The trimepranol dose thus determined was 10 mg bid for three patients, 20 mg bid for twelve patients and 40 mg bid for ten patients. The subsequent double-blind cross-over study consisted of two six weeks treatment periods, either with trimepranol followed by placebo (Group I) or in reverse order (Group II). BP and heart rate at the end of these periods were compared. Supine BP fell from 156 +/- 3/105 +/- 2 mm Hg at the end of placebo periods to 140 +/- 2/93 +/- 1 mm Hg (p less than 0.001) for systolic and diastolic BP at the end of trimepranol periods, when the data of Groups I and II are pooled. In 19 out of 25 patients, supine diastolic BP declined below 95 mmHg during the trimepranol period. A statistically significant correlation was found between the antihypertensive and bradycardic effects of trimepranol. Mild side effects occurred in the heart volumes of the patients. We conclude that bid trimepranol is an effective antihypertensive agent."}
{"id": "PMID:25851", "title": "Ultrafiltration evidence of ion binding by macromolecules in urine.", "content": "In an effort to rationalize the difference between computed estimates of urinary calcium oxalate supersaturation and estimates obtained by equilibrating urine with solid calcium oxalate, we examined ultrasfiltered urine for the binding of urinary ions. Urine was passed through a filter with a nominal passage cutoff of 1000 Daltons. The average reduction in concentration of the ultrafiltrate was 12.7 per cent for oxalate, 11.9 per cent for phosphate, 9.4 percent for calcium, 7.6 per cent for magnesium, and 6.9 per cent for sodium. From these results we conclude that calculations of urinary ion equilibrium will give better estimates if the composition of ultrafiltered urine is used.", "contents": "Ultrafiltration evidence of ion binding by macromolecules in urine. In an effort to rationalize the difference between computed estimates of urinary calcium oxalate supersaturation and estimates obtained by equilibrating urine with solid calcium oxalate, we examined ultrasfiltered urine for the binding of urinary ions. Urine was passed through a filter with a nominal passage cutoff of 1000 Daltons. The average reduction in concentration of the ultrafiltrate was 12.7 per cent for oxalate, 11.9 per cent for phosphate, 9.4 percent for calcium, 7.6 per cent for magnesium, and 6.9 per cent for sodium. From these results we conclude that calculations of urinary ion equilibrium will give better estimates if the composition of ultrafiltered urine is used."}
{"id": "PMID:25848", "title": "A behavioral approach to post-catastrophic illness work phobias.", "content": "Two patients developed work phobias following major catastrophic physical illness. A combined approach to addressing their specific fears of returning to premorbid levels of work function utilized deep muscle relaxation, imagery based desensitization, social reinforcement, and shaping techniques. A significant increase in adaptive function and decrease in depressive symptomatology resulted in both cases within six weeks after initiation of treatment.", "contents": "A behavioral approach to post-catastrophic illness work phobias. Two patients developed work phobias following major catastrophic physical illness. A combined approach to addressing their specific fears of returning to premorbid levels of work function utilized deep muscle relaxation, imagery based desensitization, social reinforcement, and shaping techniques. A significant increase in adaptive function and decrease in depressive symptomatology resulted in both cases within six weeks after initiation of treatment."}
{"id": "PMID:25852", "title": "Oxalate transport by the human small intestine.", "content": "Oxalate was transported in vitro by intestinal brush border cells from rabbit and human by a non-energy-dependent diffusion mechanism. An oxalate-binding protein that had an approximate molecular weight of 73,000 was identified in the human intestine (ileum), was localized in the cytosol cell fraction, and was affected by calcium and magnesium, which increased the oxalate binding.", "contents": "Oxalate transport by the human small intestine. Oxalate was transported in vitro by intestinal brush border cells from rabbit and human by a non-energy-dependent diffusion mechanism. An oxalate-binding protein that had an approximate molecular weight of 73,000 was identified in the human intestine (ileum), was localized in the cytosol cell fraction, and was affected by calcium and magnesium, which increased the oxalate binding."}
{"id": "PMID:25856", "title": "A quantitative cytochemical method for measuring carbonic anhydrase activity.", "content": "Components of a histochemical method for demonstrating carbonic anhydrase activity have been investigated quantitatively. It was found that it is not necessary to use free-floating sections provided the reaction is done in a reaction medium of controlled depth. This permits the use of normal cryostat sections on glass slides, so making this technique applicable to the cytochemical bioassay of gastrin. The better control of the pH of the reaction, and changes in the concentration of phosphate and of cobalt, have resulted in a quantitatively reproducible reaction in the parietal cells of guinea-pig fundus. The reaction product is measured by microdensitometry. The specificity of the carbonic anhydrase reaction has been tested by the response elicited by gastrin acting on the parietal cells in vitro and by the use of acetazolamide.", "contents": "A quantitative cytochemical method for measuring carbonic anhydrase activity. Components of a histochemical method for demonstrating carbonic anhydrase activity have been investigated quantitatively. It was found that it is not necessary to use free-floating sections provided the reaction is done in a reaction medium of controlled depth. This permits the use of normal cryostat sections on glass slides, so making this technique applicable to the cytochemical bioassay of gastrin. The better control of the pH of the reaction, and changes in the concentration of phosphate and of cobalt, have resulted in a quantitatively reproducible reaction in the parietal cells of guinea-pig fundus. The reaction product is measured by microdensitometry. The specificity of the carbonic anhydrase reaction has been tested by the response elicited by gastrin acting on the parietal cells in vitro and by the use of acetazolamide."}
{"id": "PMID:25859", "title": "Anemia as a stimulus to aortic and carotid chemoreceptors in the cat.", "content": "In cats anesthetized with alpha-chloralose, the activities of aortic and carotid chemoreceptor nerves were measured during a control period and during anemia where the hematocrit was lowered in steps by dextran-for-blood exchange. With anemia there was a sustained nonlinear increase in firing of aortic chemoreceptors. There was a greater firing of aortic chemoreceptors for a given lowering of hematocrit from an initial low blood hematocrit than for a similar decrease in hematocrit from an initial high blood hematocrit. Tonic carotid chemoreceptor firing was independent of blood hematocrit and was only transiently increased at the time of dextran-for-blood exchange. The lack of effect of anemia on carotid chemoreceptor activity appeared to be due to sympathetic nerve activity. Section of the sympathetic nerves to the carotid chemoreceptors resulted in an increase in carotid chemoreceptor afferent activity during anemia in a manner similar to the increase in aortic chemoreceptor activity.", "contents": "Anemia as a stimulus to aortic and carotid chemoreceptors in the cat. In cats anesthetized with alpha-chloralose, the activities of aortic and carotid chemoreceptor nerves were measured during a control period and during anemia where the hematocrit was lowered in steps by dextran-for-blood exchange. With anemia there was a sustained nonlinear increase in firing of aortic chemoreceptors. There was a greater firing of aortic chemoreceptors for a given lowering of hematocrit from an initial low blood hematocrit than for a similar decrease in hematocrit from an initial high blood hematocrit. Tonic carotid chemoreceptor firing was independent of blood hematocrit and was only transiently increased at the time of dextran-for-blood exchange. The lack of effect of anemia on carotid chemoreceptor activity appeared to be due to sympathetic nerve activity. Section of the sympathetic nerves to the carotid chemoreceptors resulted in an increase in carotid chemoreceptor afferent activity during anemia in a manner similar to the increase in aortic chemoreceptor activity."}
{"id": "PMID:25860", "title": "Analysis of postcapillary pH changes in blood in vivo after gas exchange.", "content": "A quantitative description of the reaction and transport processes that take place in blood during and after gas exchange in capillaries is developed and used to interpret recently reported experimental results. Included in the computation are 1) CO2-H2CO3 hydration-dehydration reactions in plasma and erythrocytes, 2) CO2 reactions with hemoglobin, 3) O2 binding to hemoglobin, 4) buffering of H+ intra- and extracellularly, 5) HCO3- Cl- exchange across the red cell membrane, 6) diffusion of gases between alveolar gas and blood, and 7) transcellular movement of water. Ion and water fluxes are described assuming passive diffusion down their electrochemical potential gradients. Recent data on the magnitude of the Bohr and Haldane shifts and on carbamate formation in the presence of 2,3-diphosphoglycerate are used. The analysis is used to examine the direction, magnitude, and time course of plasma pH changes in blood leaving the pulmonary capillaries and is shown to preduct results that agree very closely with recently reported experimental measurements in vivo. The time computed for plasma pH equilibration after gas exchange when carbonic anhydrase activity is absent from plasma is so great that blood may never be in complete electrochemical equilibrium as it travels around the circulation in normal man.", "contents": "Analysis of postcapillary pH changes in blood in vivo after gas exchange. A quantitative description of the reaction and transport processes that take place in blood during and after gas exchange in capillaries is developed and used to interpret recently reported experimental results. Included in the computation are 1) CO2-H2CO3 hydration-dehydration reactions in plasma and erythrocytes, 2) CO2 reactions with hemoglobin, 3) O2 binding to hemoglobin, 4) buffering of H+ intra- and extracellularly, 5) HCO3- Cl- exchange across the red cell membrane, 6) diffusion of gases between alveolar gas and blood, and 7) transcellular movement of water. Ion and water fluxes are described assuming passive diffusion down their electrochemical potential gradients. Recent data on the magnitude of the Bohr and Haldane shifts and on carbamate formation in the presence of 2,3-diphosphoglycerate are used. The analysis is used to examine the direction, magnitude, and time course of plasma pH changes in blood leaving the pulmonary capillaries and is shown to preduct results that agree very closely with recently reported experimental measurements in vivo. The time computed for plasma pH equilibration after gas exchange when carbonic anhydrase activity is absent from plasma is so great that blood may never be in complete electrochemical equilibrium as it travels around the circulation in normal man."}
{"id": "PMID:25875", "title": "Neutral cleanup procedure for 2,3,7,8-tetrachlorodibenzo-p-dioxin residues in bovine fat and milk.", "content": "A neutral cleanup method for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in milk and animal tissue was developed involving solvent extraction and liquid adsorption chromatography on magnesia-Celite 545, alumina, and Florisil. Cleaned up extracts were subjected to dual-ion analysis in a direct probe high resolution mass spectrometer, interfaced to a multi-channel analyzer for signal averaging. Calibration experiments were carried out with bovine milk and beef fat samples containing added TCDD. The 37CI isotopic isomer of TCDD was added as an internal standard. The response was linear for concentrations in the ppt range, with recoveries about 80%. Milk from a cow fed TCDD was cleaned up by the neutral procedure or, alternatively, a base-acid extraction procedure. The TCDD recoveries for both procedures were essentially the same. Recoveries of TCDD from liver samples of a rat given 14C-TCDD intraperitoneally, subjected to neutral cleanup and radioactive counting, were about 70%.", "contents": "Neutral cleanup procedure for 2,3,7,8-tetrachlorodibenzo-p-dioxin residues in bovine fat and milk. A neutral cleanup method for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in milk and animal tissue was developed involving solvent extraction and liquid adsorption chromatography on magnesia-Celite 545, alumina, and Florisil. Cleaned up extracts were subjected to dual-ion analysis in a direct probe high resolution mass spectrometer, interfaced to a multi-channel analyzer for signal averaging. Calibration experiments were carried out with bovine milk and beef fat samples containing added TCDD. The 37CI isotopic isomer of TCDD was added as an internal standard. The response was linear for concentrations in the ppt range, with recoveries about 80%. Milk from a cow fed TCDD was cleaned up by the neutral procedure or, alternatively, a base-acid extraction procedure. The TCDD recoveries for both procedures were essentially the same. Recoveries of TCDD from liver samples of a rat given 14C-TCDD intraperitoneally, subjected to neutral cleanup and radioactive counting, were about 70%."}
{"id": "PMID:25876", "title": "Atomic absorption spectroscopic determination of lead extracted from acid-solubilized tissues.", "content": "A method is presented for determining lead in a variety of tissues. Lyophilized samples are solubilized with nitric acid at room temperature in glass screw-cap culture tubes. Following neutralization with sodium hydroxide and sodium bicarbonate, the lead is extracted into methyl isobutyl ketone as the pyrrolidine dithiocarbamate complex and analyzed by flame atomic absorption spectrophotometry. Brain, heart, liver, lung, and spleen gave recoveries ranging from 92 to 102% with standard deviations of less than 8%. Aorta, kidney, and rib were unsuitable for analysis by this method. A large number of samples can be analyzed without specialized equipment or intricate experimental steps. The detection limit is 35 ng/g tissue (wet weight) and sensitivity is approximately 140 ng/g tissue (wet weight).", "contents": "Atomic absorption spectroscopic determination of lead extracted from acid-solubilized tissues. A method is presented for determining lead in a variety of tissues. Lyophilized samples are solubilized with nitric acid at room temperature in glass screw-cap culture tubes. Following neutralization with sodium hydroxide and sodium bicarbonate, the lead is extracted into methyl isobutyl ketone as the pyrrolidine dithiocarbamate complex and analyzed by flame atomic absorption spectrophotometry. Brain, heart, liver, lung, and spleen gave recoveries ranging from 92 to 102% with standard deviations of less than 8%. Aorta, kidney, and rib were unsuitable for analysis by this method. A large number of samples can be analyzed without specialized equipment or intricate experimental steps. The detection limit is 35 ng/g tissue (wet weight) and sensitivity is approximately 140 ng/g tissue (wet weight)."}
{"id": "PMID:25877", "title": "pH-induced difference spectrophotometric assay of acetazolamide, hydrochlorothiazide, and furosemide.", "content": "On the basis of pH-induced spectral changes for acetazolamide, hydrochlorothiazide, and furosemide, 3 different spectrophotometric methods are described. The methods were successfully applied to the assay of these drugs in different pharmaceutical formulations (tablets and ampoules). The accuracy of the analysis is increased by using the suggested methods as compared with conventional spectrophotometry.", "contents": "pH-induced difference spectrophotometric assay of acetazolamide, hydrochlorothiazide, and furosemide. On the basis of pH-induced spectral changes for acetazolamide, hydrochlorothiazide, and furosemide, 3 different spectrophotometric methods are described. The methods were successfully applied to the assay of these drugs in different pharmaceutical formulations (tablets and ampoules). The accuracy of the analysis is increased by using the suggested methods as compared with conventional spectrophotometry."}
{"id": "PMID:25878", "title": "Purification and characterization of extracellular soluble and membrane-bound insoluble alkaline phosphatases possessing phosphodiesterase activities in Bacillus subtilis.", "content": "A membrane-bound insoluble alkaline phosphatase (APase) and an extracellular soluble APase were purified, respectively, from a membrane preparation of Bacillus subtilis 6160-BC6, which carries a mutation to produce APase constitutively, and from a culture fluid of a mutant strain. RAN 1, isolated from strain 6160-BC6, which produces an extracellular soluble APase. The two preparations were homogeneous, as judged by sodium dodecyl sulfate discontinuous gel electrophoresis and by gel electrophoreses in the presence of 8 M urea at pH 9.3 and 4.3. RAN 1 APase was crystallized. Both preparations possessed phosphatase and phosphodiesterase activities, and their pH optima were both at 9.5. They were competitively inhibited by phosphate or arsenate and were activated by the addition of Ca2+ but not by Zn2+. The APase and alkaline phosphodiesterase activities seemed to be contained in the same protein molecule. The molecular weight of 6160-BC6 APase was estimated to be 46,000 +/- 1,000, and that of RAN 1 APase was estimated to be 45,000 +/- 1,000. The largest difference between the 6160-BC6 and RAN 1 APase's was in solubility in low-ionic-strength solutions. Present results suggest that each enzyme is composed of a single polypeptide chain and that 6160-BC6 APase aggregates in solutions of low ionic strength.", "contents": "Purification and characterization of extracellular soluble and membrane-bound insoluble alkaline phosphatases possessing phosphodiesterase activities in Bacillus subtilis. A membrane-bound insoluble alkaline phosphatase (APase) and an extracellular soluble APase were purified, respectively, from a membrane preparation of Bacillus subtilis 6160-BC6, which carries a mutation to produce APase constitutively, and from a culture fluid of a mutant strain. RAN 1, isolated from strain 6160-BC6, which produces an extracellular soluble APase. The two preparations were homogeneous, as judged by sodium dodecyl sulfate discontinuous gel electrophoresis and by gel electrophoreses in the presence of 8 M urea at pH 9.3 and 4.3. RAN 1 APase was crystallized. Both preparations possessed phosphatase and phosphodiesterase activities, and their pH optima were both at 9.5. They were competitively inhibited by phosphate or arsenate and were activated by the addition of Ca2+ but not by Zn2+. The APase and alkaline phosphodiesterase activities seemed to be contained in the same protein molecule. The molecular weight of 6160-BC6 APase was estimated to be 46,000 +/- 1,000, and that of RAN 1 APase was estimated to be 45,000 +/- 1,000. The largest difference between the 6160-BC6 and RAN 1 APase's was in solubility in low-ionic-strength solutions. Present results suggest that each enzyme is composed of a single polypeptide chain and that 6160-BC6 APase aggregates in solutions of low ionic strength."}
{"id": "PMID:25879", "title": "Oxygen-limited continuous culture and respiratory energy conservation in Escherichia coli.", "content": "Escherichia coli B was cultured continuously in succinate-minimal medium under conditions of oxygen limitation in the phauxostat. With decreasing oxygenation and consequent decreasing growth rates, the complement of terminal cytochrome oxidases changed as follows: high growth rates, cytochrome o; intermediate growth rates, cytochromes o and d; lowest growth rates, cytochromes o, d, and a1. Respiratory kinetics exhibited by nongrowing cell suspensions obtained from continuous cultures indicated that terminal oxidase activity was exhibited by cytochrome o (Km for O2 = 0.2 micron; Vmax = 1.1 to 1.5 mumol of O2 per nmol of cytochrome o per min) and cytochrome d (Km for O2 = 0.024 micron; Vmax = 0.7 mumol of O2 per nmol of cytochrome d per min). During oxygen-limited growth, the molar growth yield referred to respiration, and corrected for maintenance respiration [Yo(max)], was 12.6 g (dry weight) per g-atom of oxygen, not significantly different from the succinate-limited value of 12.0 g (dry weight) per g-atom of oxygen. The rate of maintenance respiration of the oxygen-limited culture was only 3.4 mg-atoms of O per g (dry weight) per h, some threefold less than that of the succinate-limited culture. Respiration-driven proton extrusion did not vary with the growth rate or with the complement of terminal oxidases (H+/O = 3.7; standard deviation, 0.07). We conclude that the content of terminal oxidases is without effect on the efficiency of respiratory energy conservation.", "contents": "Oxygen-limited continuous culture and respiratory energy conservation in Escherichia coli. Escherichia coli B was cultured continuously in succinate-minimal medium under conditions of oxygen limitation in the phauxostat. With decreasing oxygenation and consequent decreasing growth rates, the complement of terminal cytochrome oxidases changed as follows: high growth rates, cytochrome o; intermediate growth rates, cytochromes o and d; lowest growth rates, cytochromes o, d, and a1. Respiratory kinetics exhibited by nongrowing cell suspensions obtained from continuous cultures indicated that terminal oxidase activity was exhibited by cytochrome o (Km for O2 = 0.2 micron; Vmax = 1.1 to 1.5 mumol of O2 per nmol of cytochrome o per min) and cytochrome d (Km for O2 = 0.024 micron; Vmax = 0.7 mumol of O2 per nmol of cytochrome d per min). During oxygen-limited growth, the molar growth yield referred to respiration, and corrected for maintenance respiration [Yo(max)], was 12.6 g (dry weight) per g-atom of oxygen, not significantly different from the succinate-limited value of 12.0 g (dry weight) per g-atom of oxygen. The rate of maintenance respiration of the oxygen-limited culture was only 3.4 mg-atoms of O per g (dry weight) per h, some threefold less than that of the succinate-limited culture. Respiration-driven proton extrusion did not vary with the growth rate or with the complement of terminal oxidases (H+/O = 3.7; standard deviation, 0.07). We conclude that the content of terminal oxidases is without effect on the efficiency of respiratory energy conservation."}
{"id": "PMID:25880", "title": "Assimilatory sulfate reduction in an Escherichia coli mutant lacking thioredoxin activity.", "content": "An investigation of sulfate reduction in B tsnC*7004, a mutant of Escherichia coli lacking thioredoxin, is reported. Although thioredoxin is indispensable for the adenosine 3'-phosphate 5'-phosphosulfate (PAPS) sulfotransferase reaction under the usual conditions of assay in extracts of wild-type cells, the mutant grew as well as the wild type on sulfate, indicating that sulfate reduction is not rate limiting for growth. Another cofactor for the PAPS sulfotransferase reaction was found in extracts of the mutant that is absent from wild type cells. This cofactor was indistinguishable from thioredoxin in molecular weight but had a slightly different isoelectric point, allowing a separation of the two types of molecules by isoelectric focusing. Whereas electrons from nicotinamide adenine dinucleotide phosphate, reduced form, could be transferred via thioredoxin reductase or via glutathione and glutathione reductase to reduce thioredoxin in extracts of wild-type cells, electrons from nicotinamide adenine dinucleotide, reduced form, could only be transferred to the cofactor of the mutant via glutathione and glutathione reductase. All of the other available mutants blocked in sulfate reduction in E. coli contained normal levels of thioredoxin. The \"PAPS reductase\" mutant is shown to be blocked in the PAPS sulfotransferase reaction. We conclude that the cofactor found in mutant B tsnC*7004 is probably a mutated thioredoxin with an amino acid substitution that alters the isoelectric point and the reactivity with thioredoxin reductase.", "contents": "Assimilatory sulfate reduction in an Escherichia coli mutant lacking thioredoxin activity. An investigation of sulfate reduction in B tsnC*7004, a mutant of Escherichia coli lacking thioredoxin, is reported. Although thioredoxin is indispensable for the adenosine 3'-phosphate 5'-phosphosulfate (PAPS) sulfotransferase reaction under the usual conditions of assay in extracts of wild-type cells, the mutant grew as well as the wild type on sulfate, indicating that sulfate reduction is not rate limiting for growth. Another cofactor for the PAPS sulfotransferase reaction was found in extracts of the mutant that is absent from wild type cells. This cofactor was indistinguishable from thioredoxin in molecular weight but had a slightly different isoelectric point, allowing a separation of the two types of molecules by isoelectric focusing. Whereas electrons from nicotinamide adenine dinucleotide phosphate, reduced form, could be transferred via thioredoxin reductase or via glutathione and glutathione reductase to reduce thioredoxin in extracts of wild-type cells, electrons from nicotinamide adenine dinucleotide, reduced form, could only be transferred to the cofactor of the mutant via glutathione and glutathione reductase. All of the other available mutants blocked in sulfate reduction in E. coli contained normal levels of thioredoxin. The \"PAPS reductase\" mutant is shown to be blocked in the PAPS sulfotransferase reaction. We conclude that the cofactor found in mutant B tsnC*7004 is probably a mutated thioredoxin with an amino acid substitution that alters the isoelectric point and the reactivity with thioredoxin reductase."}
{"id": "PMID:25881", "title": "Identity of proline dehydrogenase and delta1-pyrroline-5-carboxylic acid reductase in Clostridium sporogenes.", "content": "Proline dehydrogenase and delta1-pyrroline-5-carboxylic acid (PCA) reductase activities were copurified 60- and 130-fold, respectively, from extracts of Clostridium sporogenes. The primary change in the ratio of activites was the result of a loss of proline dehydrogenase activity during dialysis. Both activities were eluted in single peaks from diethylaminoethyl-cellulose, hydroxylapatite, and Sephadex G-200 columns. They had identical sedimentation coefficients (10.3S), as determined in linear sucrose gradients, and identical isoelectric points (4.95 to 5.12) based on isoelectric focusing. The proline dehydrogenase activity was dependent on nicotinamide adenine dinucleotide and L-proline, and the PCA reductase required L-PCA and reduced nicotinamide adenine dinucleotide. The optimum pH for the assay of proline dehydrogenase was approximately 10.2, whereas that for PCA reductase was 6.5 to 7.5. An increase in pH from 8.0 to 10.2 greatly decreased the apparent Michaelis constant observed for L-proline, and an increase from pH 8.3 to 8.6 resulted in a large shift in the reaction equilibrium toward PCA. Both the dehydrogenase and reductase activities were stabilized to heating at 65 degrees C for 5 min by solutes of high ionic strength and were inactivated in a similar fashion when dissolved in low-ionic-strength buffer. The specific activities for both were reduced by about 50% when glucose was added to the growth medium. The data support the conclusion that L-proline and L-PCA are interconverted by either a single enzyme or an enzyme complex in extracts of C. sporogenes cells.", "contents": "Identity of proline dehydrogenase and delta1-pyrroline-5-carboxylic acid reductase in Clostridium sporogenes. Proline dehydrogenase and delta1-pyrroline-5-carboxylic acid (PCA) reductase activities were copurified 60- and 130-fold, respectively, from extracts of Clostridium sporogenes. The primary change in the ratio of activites was the result of a loss of proline dehydrogenase activity during dialysis. Both activities were eluted in single peaks from diethylaminoethyl-cellulose, hydroxylapatite, and Sephadex G-200 columns. They had identical sedimentation coefficients (10.3S), as determined in linear sucrose gradients, and identical isoelectric points (4.95 to 5.12) based on isoelectric focusing. The proline dehydrogenase activity was dependent on nicotinamide adenine dinucleotide and L-proline, and the PCA reductase required L-PCA and reduced nicotinamide adenine dinucleotide. The optimum pH for the assay of proline dehydrogenase was approximately 10.2, whereas that for PCA reductase was 6.5 to 7.5. An increase in pH from 8.0 to 10.2 greatly decreased the apparent Michaelis constant observed for L-proline, and an increase from pH 8.3 to 8.6 resulted in a large shift in the reaction equilibrium toward PCA. Both the dehydrogenase and reductase activities were stabilized to heating at 65 degrees C for 5 min by solutes of high ionic strength and were inactivated in a similar fashion when dissolved in low-ionic-strength buffer. The specific activities for both were reduced by about 50% when glucose was added to the growth medium. The data support the conclusion that L-proline and L-PCA are interconverted by either a single enzyme or an enzyme complex in extracts of C. sporogenes cells."}
{"id": "PMID:25882", "title": "Role of Na+ and Li+ in thiomethylgalactoside transport by the melibiose transport system of Escherichia coli.", "content": "Thiomethyl-beta-galactoside (TMG) accumulation via the melibiose transport system was studied in lactose transport-negative strains of Escherichia coli. TMG uptake by either intact cells or membrane vesicles was markedly stimulated by Na+ or Li+ between pH 5.5 and 8. The Km for uptake of TMG was approximately 0.2 mM at an external Na+ concentration of 5 mM (pH 7). The alpha-galactosides, melibiose, methyl-alpha-galactoside, and o-nitrophenyl-alpha-galactoside had a high affinity for this system whereas lactose, maltose and glucose had none. Evidence is presented for Li+-TMG or Na+-TMG cotransport.", "contents": "Role of Na+ and Li+ in thiomethylgalactoside transport by the melibiose transport system of Escherichia coli. Thiomethyl-beta-galactoside (TMG) accumulation via the melibiose transport system was studied in lactose transport-negative strains of Escherichia coli. TMG uptake by either intact cells or membrane vesicles was markedly stimulated by Na+ or Li+ between pH 5.5 and 8. The Km for uptake of TMG was approximately 0.2 mM at an external Na+ concentration of 5 mM (pH 7). The alpha-galactosides, melibiose, methyl-alpha-galactoside, and o-nitrophenyl-alpha-galactoside had a high affinity for this system whereas lactose, maltose and glucose had none. Evidence is presented for Li+-TMG or Na+-TMG cotransport."}
{"id": "PMID:25883", "title": "Purification and characterization of a secondary alcohol dehydrogenase from a pseudomonad.", "content": "Growth of Pseudomonas sp. NRRL B3266 in the presence of oleic acid resulted in the induction of two enzymes: oleate hydratase, which produced 10(R)hydroxyoctadecanoate, and hydroxyoctadecanoate dehydrogenase, which catalyzed the oxidized nicotinamide adenine dinucleotide-dependent production of 10-oxooctadecanoate. This latter enzyme was purified to homogeneity and shown to consist of two polypeptide chains of about 29,000 daltons each. The enzyme had a broad substrate specificity, catalyzing the dehydrogenation of a number of 18-carbon hydroxy fatty acids. The kinetic parameters for various 10- and 12-hydroxy fatty acids were similar (Km ca. 5 micron and Vmax ca. 50 to 200 mumol/min per mg of protein). The enzyme also catalyzed the dehydrogenation of unsubstituted secondary alcohols. The effectiveness of these alcohols as substrates was highly dependent on their hydrophobicity, the Km decreasing from 9 mM for 4-heptanol to 7 micron for 6-dodecanol. Inhibition of the enzyme by primary alcohols also showed a dependence on hydrophobicity, the Ki decreasing from 350 mM for methanol to 90 micron for decanol.", "contents": "Purification and characterization of a secondary alcohol dehydrogenase from a pseudomonad. Growth of Pseudomonas sp. NRRL B3266 in the presence of oleic acid resulted in the induction of two enzymes: oleate hydratase, which produced 10(R)hydroxyoctadecanoate, and hydroxyoctadecanoate dehydrogenase, which catalyzed the oxidized nicotinamide adenine dinucleotide-dependent production of 10-oxooctadecanoate. This latter enzyme was purified to homogeneity and shown to consist of two polypeptide chains of about 29,000 daltons each. The enzyme had a broad substrate specificity, catalyzing the dehydrogenation of a number of 18-carbon hydroxy fatty acids. The kinetic parameters for various 10- and 12-hydroxy fatty acids were similar (Km ca. 5 micron and Vmax ca. 50 to 200 mumol/min per mg of protein). The enzyme also catalyzed the dehydrogenation of unsubstituted secondary alcohols. The effectiveness of these alcohols as substrates was highly dependent on their hydrophobicity, the Km decreasing from 9 mM for 4-heptanol to 7 micron for 6-dodecanol. Inhibition of the enzyme by primary alcohols also showed a dependence on hydrophobicity, the Ki decreasing from 350 mM for methanol to 90 micron for decanol."}
{"id": "PMID:25884", "title": "Purification and characterization of a hyaluronidase associated with a temperate bacteriophage of group A, type 49 streptococci.", "content": "Urea treatment of a temperate bacteriophage from a type 49 strain of group A streptococcus (Streptococcus pyogenes) followed by ammonium sulfate fractionation, ion exchange, and affinity chromatography of solubilized proteins provided for the recovery (12%) and purification (44-fold) of the phage-associated hyaluronidase. The molecular weight of the homogeneous, purified enzyme was estimated to be 71,000 by polyacrylamide gel electrophoresis (in the presence of sodium dodecyl sulfate) and 75,000 by gel filtration with Sephacryl S-200. The enzyme has a pH optimum of 5.5, a Vmax of 0.1 absorbance unit/min per microgram of protein, and a Km of 4.8 X 10(-2) mg/ml with umbilical cord hyaluronic acid as substrate. Of the cations tested, calcium and magnesium were the only effectors of the enzyme. The enzyme is a glycoprotein (7.25% carbohydrate) containing glucose, galactose, and glucosamine. Analysis of the amino acid composition revealed a predominance of acidic amino acids and a relatively high content of cysteine. The partial specific volume, estimated from the amino acid and sugar analyses, was 0.725 cm3/g.", "contents": "Purification and characterization of a hyaluronidase associated with a temperate bacteriophage of group A, type 49 streptococci. Urea treatment of a temperate bacteriophage from a type 49 strain of group A streptococcus (Streptococcus pyogenes) followed by ammonium sulfate fractionation, ion exchange, and affinity chromatography of solubilized proteins provided for the recovery (12%) and purification (44-fold) of the phage-associated hyaluronidase. The molecular weight of the homogeneous, purified enzyme was estimated to be 71,000 by polyacrylamide gel electrophoresis (in the presence of sodium dodecyl sulfate) and 75,000 by gel filtration with Sephacryl S-200. The enzyme has a pH optimum of 5.5, a Vmax of 0.1 absorbance unit/min per microgram of protein, and a Km of 4.8 X 10(-2) mg/ml with umbilical cord hyaluronic acid as substrate. Of the cations tested, calcium and magnesium were the only effectors of the enzyme. The enzyme is a glycoprotein (7.25% carbohydrate) containing glucose, galactose, and glucosamine. Analysis of the amino acid composition revealed a predominance of acidic amino acids and a relatively high content of cysteine. The partial specific volume, estimated from the amino acid and sugar analyses, was 0.725 cm3/g."}
{"id": "PMID:25885", "title": "Enolase from spores and cells of Bacillus megaterium: two-step purification of the enzyme and some of its properties.", "content": "A simple two-step procedure for purification of enolase from germinated spores or vegetative cells of Bacillus megaterium is described. The procedure resulted in a 1,200-fold purification with production of homogeneous enzyme in approximately 75% yield; the enzymes from spores and cells seemed identical. The molecular weight of the native enzyme was 335,000, with a subunit molecular weight of 42,000. The enzyme required Mg2+ and was inhibited by ethylenediaminetetraacetic acid and fluoride ions. The Michaelis constants for 2-phosphoglyceric acid and Mg2+ were 7.1 X 10(-4) and 4.7 X 10(-4) M, respectively.", "contents": "Enolase from spores and cells of Bacillus megaterium: two-step purification of the enzyme and some of its properties. A simple two-step procedure for purification of enolase from germinated spores or vegetative cells of Bacillus megaterium is described. The procedure resulted in a 1,200-fold purification with production of homogeneous enzyme in approximately 75% yield; the enzymes from spores and cells seemed identical. The molecular weight of the native enzyme was 335,000, with a subunit molecular weight of 42,000. The enzyme required Mg2+ and was inhibited by ethylenediaminetetraacetic acid and fluoride ions. The Michaelis constants for 2-phosphoglyceric acid and Mg2+ were 7.1 X 10(-4) and 4.7 X 10(-4) M, respectively."}
{"id": "PMID:25886", "title": "Differences between agonist and antagonist binding following beta-adrenergic receptor desensitization.", "content": "The specific beta-adrenergic agonist radioligand (+/-)-[3H]hydroxybenzylisoproterenol ([3H]HBI) was used to investigate alterations in the beta-adrenergic receptors of frog erythrocytes occurring during the process of agonist-induced, receptor-specific desensitization. There was close agreement between the percentage fall in [3H]HBI binding and that in catecholamine-stimulated adenylate cyclase activity following periods of preincubation of up to 7 h with 0.1 mM (-)-isoproterenol. Desensitization was maximal by 5 h, resulting in a 69% reduction in [3H]HBI binding and a 67% reduction in isoproterenol-stimulated adenylate cyclase activity. In contrast, binding of the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol was significantly less affected by desensitization (p is less than 0.05 at 2 1/2, 5, and 7 h), showing a maximum reduction in binding of only 35% in these experiments. The consistent close agreement of reduction in agonist binding with that in hormone-stimulated adenylate cyclase activity, together with the significant difference observed between agonist and antagonist binding, implies that an alteration occurs during desensitization which preferentially interferes with agonist binding, while antagonist binding is less affected. The locus of this agonist-specific alteration may be the receptor binding site or a site involved in receptor-enzyme coupling. Agonist binding studies may now be used to assess more completely the desensitized state of beta-adrenergic receptors in systems in which marked desensitization of beta-adrenergic responses is associated with little or no reduction in antagonist binding.", "contents": "Differences between agonist and antagonist binding following beta-adrenergic receptor desensitization. The specific beta-adrenergic agonist radioligand (+/-)-[3H]hydroxybenzylisoproterenol ([3H]HBI) was used to investigate alterations in the beta-adrenergic receptors of frog erythrocytes occurring during the process of agonist-induced, receptor-specific desensitization. There was close agreement between the percentage fall in [3H]HBI binding and that in catecholamine-stimulated adenylate cyclase activity following periods of preincubation of up to 7 h with 0.1 mM (-)-isoproterenol. Desensitization was maximal by 5 h, resulting in a 69% reduction in [3H]HBI binding and a 67% reduction in isoproterenol-stimulated adenylate cyclase activity. In contrast, binding of the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol was significantly less affected by desensitization (p is less than 0.05 at 2 1/2, 5, and 7 h), showing a maximum reduction in binding of only 35% in these experiments. The consistent close agreement of reduction in agonist binding with that in hormone-stimulated adenylate cyclase activity, together with the significant difference observed between agonist and antagonist binding, implies that an alteration occurs during desensitization which preferentially interferes with agonist binding, while antagonist binding is less affected. The locus of this agonist-specific alteration may be the receptor binding site or a site involved in receptor-enzyme coupling. Agonist binding studies may now be used to assess more completely the desensitized state of beta-adrenergic receptors in systems in which marked desensitization of beta-adrenergic responses is associated with little or no reduction in antagonist binding."}
{"id": "PMID:25887", "title": "Acetyl-CoA carboxylase. Evidence for polymeric filament to protomer transition in the intact avian liver cell.", "content": "Digitonin treatment of chick liver cells in monolayer culture perforates the plasma membrane, causing release of acetyl-CoA carboxylase and other cytosolic enzymes. The rate of carboxylase release is affected by conditions known to alter the position of the protomer-polymer (filament) equilibrium of the enzyme. Citrate, an allosteric activator of the carboxylase, induces polymerization of the protomeric avidin-sensitive form giving rise to the avidin-insensitive polymeric filamentous form. When cells are exposed to N6,O2-dibutyryl cyclic adenosine 3':5'-monophosphate which lowers intracellular citrate levels, the rate of carboxylase release from digitonin-treated cells is greatly accelerated. The presence of avidin, which rapidly enters the cell during digitonin treatment, inactivates carboxylase under conditions that promote depolymerization and rapid release, but not under conditions which promote polymerization and slow release. These findings indicate that carboxylase filaments exist in the intact chick liver cell when the cytoplasmic citrate level is high and undergo depolymerization when citrate levels fall.", "contents": "Acetyl-CoA carboxylase. Evidence for polymeric filament to protomer transition in the intact avian liver cell. Digitonin treatment of chick liver cells in monolayer culture perforates the plasma membrane, causing release of acetyl-CoA carboxylase and other cytosolic enzymes. The rate of carboxylase release is affected by conditions known to alter the position of the protomer-polymer (filament) equilibrium of the enzyme. Citrate, an allosteric activator of the carboxylase, induces polymerization of the protomeric avidin-sensitive form giving rise to the avidin-insensitive polymeric filamentous form. When cells are exposed to N6,O2-dibutyryl cyclic adenosine 3':5'-monophosphate which lowers intracellular citrate levels, the rate of carboxylase release from digitonin-treated cells is greatly accelerated. The presence of avidin, which rapidly enters the cell during digitonin treatment, inactivates carboxylase under conditions that promote depolymerization and rapid release, but not under conditions which promote polymerization and slow release. These findings indicate that carboxylase filaments exist in the intact chick liver cell when the cytoplasmic citrate level is high and undergo depolymerization when citrate levels fall."}
{"id": "PMID:25889", "title": "Hemoglobins of the killifish Fundulus heteroclitus. Separation, characterization, and a model for the subunit compositions.", "content": "Polyacrylamide and starch gel electrophoresis of the hemoglobin of the killifish Fundulus heteroclitus reveal the presence of four clearly distinguishable components. These isohemoglobins, each tetramers consisting of alpha and beta chains, can be preparatively separated by ion exchange chromatography on DEAE-cellulose and are homogeneous according to isoelectric focusing in polyacrylamide gels. Oxygen equilibria of the isolated hemoglobin components (Hb I, Hb II, Hb III, and Hb IV) show only minor differences in the magnitude of the Bohr effect and in the effect of ATP on the binding of oxygen. Four different globin chains, alphaa, alphab, betaa, and betab, can be separated by ion exchange on CM-cellulose. Hb I is a homotetramer of alphab and betab chains, Hb IV consists of alphaa and betaa subunits, and components II and III are heterotetramers consisting of all four chains. The alpha and beta chains differ significantly in amino acid composition. A model suggesting the existence of 10 different isohemoglobins, 6 of which have stable intersubunit contacts, has been proposed to account for the qualitative and quantitative aspects of the electrophoretic behavior of the components. Separations of the isohemoglobins on DEAE-cellulose under slightly modified conditions provide additional support for the model.", "contents": "Hemoglobins of the killifish Fundulus heteroclitus. Separation, characterization, and a model for the subunit compositions. Polyacrylamide and starch gel electrophoresis of the hemoglobin of the killifish Fundulus heteroclitus reveal the presence of four clearly distinguishable components. These isohemoglobins, each tetramers consisting of alpha and beta chains, can be preparatively separated by ion exchange chromatography on DEAE-cellulose and are homogeneous according to isoelectric focusing in polyacrylamide gels. Oxygen equilibria of the isolated hemoglobin components (Hb I, Hb II, Hb III, and Hb IV) show only minor differences in the magnitude of the Bohr effect and in the effect of ATP on the binding of oxygen. Four different globin chains, alphaa, alphab, betaa, and betab, can be separated by ion exchange on CM-cellulose. Hb I is a homotetramer of alphab and betab chains, Hb IV consists of alphaa and betaa subunits, and components II and III are heterotetramers consisting of all four chains. The alpha and beta chains differ significantly in amino acid composition. A model suggesting the existence of 10 different isohemoglobins, 6 of which have stable intersubunit contacts, has been proposed to account for the qualitative and quantitative aspects of the electrophoretic behavior of the components. Separations of the isohemoglobins on DEAE-cellulose under slightly modified conditions provide additional support for the model."}
{"id": "PMID:25890", "title": "Hydrogen exchange kinetics of human hemoglobins. The pH dependence of solvent accessibility in cyanomet-, oxy-, and deoxyhemoglobin.", "content": "The hydrogen exchange kinetics of human oxy-, deoxy-, and cyanomethemoglobin have been measured as a function of pH by the tritium tracer method. At 5 degrees C and in phosphate buffer both liganded and unliganded forms of ferrohemoglobin exhibit deviations from the regular pH dependence of exchange that is characteristic of cyanomethemoglobin. In oxyhemoglobin, the deviation from the normal exchange pattern is centered at pH 7.4 and is in the direction of increased exchange or solvent accessibility. The effect in deoxyhemogloin, while occurring at the same pH and being of the same order of magnitude, is in the opposite direction, thus suggesting a pH-induced conformational transition leading to a less accessible structure. The width of these pH-induced deviations in solvent accessibility is approximately 1 pH unit in both cases. We propose a model in which specific interactions between charged groups in both froms of ferrohemoglobin account for these deviations.", "contents": "Hydrogen exchange kinetics of human hemoglobins. The pH dependence of solvent accessibility in cyanomet-, oxy-, and deoxyhemoglobin. The hydrogen exchange kinetics of human oxy-, deoxy-, and cyanomethemoglobin have been measured as a function of pH by the tritium tracer method. At 5 degrees C and in phosphate buffer both liganded and unliganded forms of ferrohemoglobin exhibit deviations from the regular pH dependence of exchange that is characteristic of cyanomethemoglobin. In oxyhemoglobin, the deviation from the normal exchange pattern is centered at pH 7.4 and is in the direction of increased exchange or solvent accessibility. The effect in deoxyhemogloin, while occurring at the same pH and being of the same order of magnitude, is in the opposite direction, thus suggesting a pH-induced conformational transition leading to a less accessible structure. The width of these pH-induced deviations in solvent accessibility is approximately 1 pH unit in both cases. We propose a model in which specific interactions between charged groups in both froms of ferrohemoglobin account for these deviations."}
{"id": "PMID:25891", "title": "Enzymatic methylation of carboxyl groups of chromaffin granule membrane proteins.", "content": "Carboxyl groups of membrane and soluble proteins from bovine adrenal medulla chromaffin granules were enzymatically methylated. The methylated peptides were resolved using gel electrophoresis under acidic conditions in the presence of N-cetylpyridinium chloride. There was a selective methylation of two groups of membrane peptides which did not correspond to any of the chromaffin granule soluble proteins. Dopamine beta-hydroxylase, an acidic protein accounting for up to 25% of the membrane proteins, was a poor substrate for protein carboxylmethylase. The methyl esters of membrane proteins were more labile than those of the chromaffin granule soluble proteins. At all pH values tested, membrane protein-methyl esters were hydrolyzed three times more rapidly than the soluble protein-methyl esters.", "contents": "Enzymatic methylation of carboxyl groups of chromaffin granule membrane proteins. Carboxyl groups of membrane and soluble proteins from bovine adrenal medulla chromaffin granules were enzymatically methylated. The methylated peptides were resolved using gel electrophoresis under acidic conditions in the presence of N-cetylpyridinium chloride. There was a selective methylation of two groups of membrane peptides which did not correspond to any of the chromaffin granule soluble proteins. Dopamine beta-hydroxylase, an acidic protein accounting for up to 25% of the membrane proteins, was a poor substrate for protein carboxylmethylase. The methyl esters of membrane proteins were more labile than those of the chromaffin granule soluble proteins. At all pH values tested, membrane protein-methyl esters were hydrolyzed three times more rapidly than the soluble protein-methyl esters."}
{"id": "PMID:25894", "title": "Characterization of the low density lipoprotein receptor in membranes prepared from human fibroblasts.", "content": "An ultracentrifugation assay has been developed to measure low density lipoprotein (LDL) receptor activity in membranes prepared from cultured human fibroblasts. The binding site for 125I-labeled LDL in isolated membranes reflected the properties of the LDL receptor previously demonstrated in intact fibroblasts. It exhibited high affinity (Kd approximately 4 microgram of LDL protein/ml), specificity (LDL approximately 400-fold more effective than high density lipoprotein in competing with 125I-LDL for the binding site), dependence on calcium, and susceptibility to destruction by pronase. The number of LDL receptors detected in the in vitro membrane binding assay was similar to the number detected in intact cells. The number of receptors was reduced in membranes from fibroblasts that were grown in the presence of 25-hydroxycholesterol plus cholesterol and in fibroblast membranes from a subject with homozygous familial hypercholesterolemia, two situations in which the number of LDL receptors in intact fibroblasts is known to be reduced. The availability of a membrane binding assay that faithfully reflects the properties of the physiologic LDL receptor of intact cells should permit the characterization of this receptor in organs from intact humans and animals.", "contents": "Characterization of the low density lipoprotein receptor in membranes prepared from human fibroblasts. An ultracentrifugation assay has been developed to measure low density lipoprotein (LDL) receptor activity in membranes prepared from cultured human fibroblasts. The binding site for 125I-labeled LDL in isolated membranes reflected the properties of the LDL receptor previously demonstrated in intact fibroblasts. It exhibited high affinity (Kd approximately 4 microgram of LDL protein/ml), specificity (LDL approximately 400-fold more effective than high density lipoprotein in competing with 125I-LDL for the binding site), dependence on calcium, and susceptibility to destruction by pronase. The number of LDL receptors detected in the in vitro membrane binding assay was similar to the number detected in intact cells. The number of receptors was reduced in membranes from fibroblasts that were grown in the presence of 25-hydroxycholesterol plus cholesterol and in fibroblast membranes from a subject with homozygous familial hypercholesterolemia, two situations in which the number of LDL receptors in intact fibroblasts is known to be reduced. The availability of a membrane binding assay that faithfully reflects the properties of the physiologic LDL receptor of intact cells should permit the characterization of this receptor in organs from intact humans and animals."}
{"id": "PMID:25896", "title": "Isolation and characterization of ornithine transcarbamylase from normal human liver.", "content": "We report experiments describing the isolation and characterization of ornithine transcarbamylase from normal human liver. Our preparative procedure employs initial centrifugation and heat steps, intermediate batch-wise adsorption and desorption from ion exchange resins and column chromatographic elution from hydroxylapatite, and final purification by gel filtration chromatography and glycerol density gradient centrifugation. The enzyme, purified 580-fold in this way, is homogeneous as judged by native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human ornithine transcarbamylase has a molecular weight of 114,000 and is a trimer of identical 38,000 molecular weight subunits. It focuses at pH 6.8 as a single band on polyacrylamide gel, has a COOH-terminal phenylalanine, an NH2-terminal glycine, an apparent Km for L-ornithine of 0.4 mM and for carbamyl phosphate of 0.16 mM, and a pH optimum of 7.7. The enzyme is quite stable over a temperature range from -50 degrees to +60 degrees C and over the pH range from 5.8 to 8.2. The quaternary structure and amino acid composition of the human enzyme are very similar to those of its bovine homologue.", "contents": "Isolation and characterization of ornithine transcarbamylase from normal human liver. We report experiments describing the isolation and characterization of ornithine transcarbamylase from normal human liver. Our preparative procedure employs initial centrifugation and heat steps, intermediate batch-wise adsorption and desorption from ion exchange resins and column chromatographic elution from hydroxylapatite, and final purification by gel filtration chromatography and glycerol density gradient centrifugation. The enzyme, purified 580-fold in this way, is homogeneous as judged by native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human ornithine transcarbamylase has a molecular weight of 114,000 and is a trimer of identical 38,000 molecular weight subunits. It focuses at pH 6.8 as a single band on polyacrylamide gel, has a COOH-terminal phenylalanine, an NH2-terminal glycine, an apparent Km for L-ornithine of 0.4 mM and for carbamyl phosphate of 0.16 mM, and a pH optimum of 7.7. The enzyme is quite stable over a temperature range from -50 degrees to +60 degrees C and over the pH range from 5.8 to 8.2. The quaternary structure and amino acid composition of the human enzyme are very similar to those of its bovine homologue."}
{"id": "PMID:25898", "title": "Changes in hepatic levels of tyrosine aminotransferase messenger RNA during induction by hydrocortisone.", "content": "Messenger RNA specific for tyrosine aminotransferase was quantitated by microinjection into oocytes of Xenopus laevis. The heterologously translated enzyme was identified by specific immunoprecipitation and found to be identical with authentic aminotransferase by several criteria. The level of functional message present in rat liver increases during hydrocortisone induction, and this increase is directly proportional to the increased rate of synthesis of the enzyme. Kinetic analysis of the changes in tyrosine aminotransferase mRNA levels during induction and withdrawal indicates that the steroid does not affect the stability of the message, which has a half-life of approximately 1.2 h. Hydrocortisone, therefore, acts to increase the rate of synthesis of the specific messenger by stimulating either its transcription or processing to functional mRNA.", "contents": "Changes in hepatic levels of tyrosine aminotransferase messenger RNA during induction by hydrocortisone. Messenger RNA specific for tyrosine aminotransferase was quantitated by microinjection into oocytes of Xenopus laevis. The heterologously translated enzyme was identified by specific immunoprecipitation and found to be identical with authentic aminotransferase by several criteria. The level of functional message present in rat liver increases during hydrocortisone induction, and this increase is directly proportional to the increased rate of synthesis of the enzyme. Kinetic analysis of the changes in tyrosine aminotransferase mRNA levels during induction and withdrawal indicates that the steroid does not affect the stability of the message, which has a half-life of approximately 1.2 h. Hydrocortisone, therefore, acts to increase the rate of synthesis of the specific messenger by stimulating either its transcription or processing to functional mRNA."}
{"id": "PMID:25900", "title": "Magnesium-induced inner membrane aggregation in heart mitochondria.", "content": "Mg(2+) at an optimal concentration of 2mM (ph 6.5) induces large increases (up to 30 percent) in the optical density of bovine heart mitochondria incubated under conditions of low ionic strength (< approx. 0.01). The increases are associated with aggregation (sticking together) of the inner membranes and are little affected by changes in the energy status of the mitochondria. Virtually all of a number of other polyvalent cations tested and Ag(+) induce increases in mitochondrial optical density similar to those induced by Mg(2+), their approximate order of concentration effectiveness in respect to Mg(2+) being: La(3+) > Pb(2+) = Cu(2+) > Cd(2+) > Zn(2+) > Ag(+) > Mn(2+) > Ca(2+) > Mg(2+). With the exception of Mg(2+), all of these cations appear to induce swelling of the mitochondria concomitant with inner membrane aggregation. The inhibitors of the adenine nucleotide transport reaction carboxyatratyloside and bongkrekic acid are capable of preventing and reversing Mg(2+)-induced aggregation at the same low concentration required for complete inhibition of phosphorylating respiration, suggesting that they inhibit the aggregation by binding to the adenine nucleotide carrier. The findings are interpreted to indicate (a) that the inner mitochondrial membrane is normally prevented from aggregating by virtue of its net negative outer surface change, (b) that the cations induce the membrane to aggregate by binding at its outer surface, decreasing the net negative charge, and (c) that carboxyatractyloside and bongkrekic acid inhibit the aggregation by binding to the outer surface of the membrane, increasing the net negative charge.", "contents": "Magnesium-induced inner membrane aggregation in heart mitochondria. Mg(2+) at an optimal concentration of 2mM (ph 6.5) induces large increases (up to 30 percent) in the optical density of bovine heart mitochondria incubated under conditions of low ionic strength (< approx. 0.01). The increases are associated with aggregation (sticking together) of the inner membranes and are little affected by changes in the energy status of the mitochondria. Virtually all of a number of other polyvalent cations tested and Ag(+) induce increases in mitochondrial optical density similar to those induced by Mg(2+), their approximate order of concentration effectiveness in respect to Mg(2+) being: La(3+) > Pb(2+) = Cu(2+) > Cd(2+) > Zn(2+) > Ag(+) > Mn(2+) > Ca(2+) > Mg(2+). With the exception of Mg(2+), all of these cations appear to induce swelling of the mitochondria concomitant with inner membrane aggregation. The inhibitors of the adenine nucleotide transport reaction carboxyatratyloside and bongkrekic acid are capable of preventing and reversing Mg(2+)-induced aggregation at the same low concentration required for complete inhibition of phosphorylating respiration, suggesting that they inhibit the aggregation by binding to the adenine nucleotide carrier. The findings are interpreted to indicate (a) that the inner mitochondrial membrane is normally prevented from aggregating by virtue of its net negative outer surface change, (b) that the cations induce the membrane to aggregate by binding at its outer surface, decreasing the net negative charge, and (c) that carboxyatractyloside and bongkrekic acid inhibit the aggregation by binding to the outer surface of the membrane, increasing the net negative charge."}
{"id": "PMID:25901", "title": "Polymerization of actin. IV. Role of Ca++ and H+ in the assembly of actin and in membrane fusion in the acrosomal reaction of echinoderm sperm.", "content": "When Pisaster, Asterias, or Thyone sperm are treated with the ionophore A23187 or X537A, an acrosomal reaction similar but not identical to a normal acrosomal reaction is induced in all the sperm. Based upon the response of the sperm, the acrosomal reaction consists of a series of temporally related steps. These include the fusion of the acrosomal vacuole with the cell surface, the polymerization of the actin, the alignment of the actin filaments, an increase in volume, an increase in the limiting membrane, and changes in the shape of the nucleus. In this report, we have concentrated on the first two steps in this sequence. Although fusion of the acrosomal vacuole with the cell surface requires Ca++, we found that the polymerization of actin instead appears to be dependent upon an increase in intracellular pH. This conclusion was reached by applying to sperm A23187, X537A, or nigericin, ionophores which all carry H+ at high affinity, yet vary in their affinity for other cations. When sperm are suspended in isotonic NaCl, isotonic KCl, calcium-free seawater, or seawater, all at pH 8.0, and the ionophore is added, the actin polymerizes explosively and an efflux of H+ from the cell occurs. However, if the pH, of the external medium is maintained at 6.5, the presumed intracellular pH, no effect is observed. And, finally, if egg jelly is added to sperm (the natural stimulus for the acrosomal reaction) at pH 8.0, H+ is also released. On the basis of these observations and those presented in earlier papers in this series, we conclude that a rise in intracellular pH induces the actin to disassociate from its binding proteins. Now it can polymerize.", "contents": "Polymerization of actin. IV. Role of Ca++ and H+ in the assembly of actin and in membrane fusion in the acrosomal reaction of echinoderm sperm. When Pisaster, Asterias, or Thyone sperm are treated with the ionophore A23187 or X537A, an acrosomal reaction similar but not identical to a normal acrosomal reaction is induced in all the sperm. Based upon the response of the sperm, the acrosomal reaction consists of a series of temporally related steps. These include the fusion of the acrosomal vacuole with the cell surface, the polymerization of the actin, the alignment of the actin filaments, an increase in volume, an increase in the limiting membrane, and changes in the shape of the nucleus. In this report, we have concentrated on the first two steps in this sequence. Although fusion of the acrosomal vacuole with the cell surface requires Ca++, we found that the polymerization of actin instead appears to be dependent upon an increase in intracellular pH. This conclusion was reached by applying to sperm A23187, X537A, or nigericin, ionophores which all carry H+ at high affinity, yet vary in their affinity for other cations. When sperm are suspended in isotonic NaCl, isotonic KCl, calcium-free seawater, or seawater, all at pH 8.0, and the ionophore is added, the actin polymerizes explosively and an efflux of H+ from the cell occurs. However, if the pH, of the external medium is maintained at 6.5, the presumed intracellular pH, no effect is observed. And, finally, if egg jelly is added to sperm (the natural stimulus for the acrosomal reaction) at pH 8.0, H+ is also released. On the basis of these observations and those presented in earlier papers in this series, we conclude that a rise in intracellular pH induces the actin to disassociate from its binding proteins. Now it can polymerize."}
{"id": "PMID:25902", "title": "Polymerization of actin. V. A new organelle, the actomere, that initates the assembly of actin filaments in Thyone sperm.", "content": "Between the acrosomal vacuole and the nucleus is a cup of amorphous material (profilactin) which is transformed into filaments during the acrosomal reaction. In the center of this cup in untreated Thyone sperm is a dense material which I refer to as the actomere; it is composed of 20-25 filaments embedded in a dense matrix. To visualize the substructure of the actomere, the profilactin around it must be removed. This is achieved either by demembranating the sperm with Triton X-100 and then raising the pH to 8.0, or by adding inophores to intact sperm at pH 8.0. Under these conditions, the actomere remains as a unit while the rest of the profilactin is solubilized or polymerized. When demembranated sperm are incubated under conditions in which the actin should polymerize, filaments grow from the end of the actomere: the actomere thus appears to behave as a nucleating body. This observation is strengthened by experiments in which untreated sperm are incubated in seawater or isotonic NaCl at pH 7.0 and the ionophore X537A is added; in this case, only a partial polymerization of the actin occurs and the acrosomal vacuole does not fuse with the cell surface. The actin filaments that do form, however, are attached to the apical end of the actomere. In fact, the elongating filaments push their way into and frequently through the acrosomal vacuole. Thus, it appears that the sperm organizes the actin filaments by controlling their nucleation. My model is that the cell controls the ammount of unbound actin such that it is slightly above the critical concentration for polymerization. Then, spontaneous nucleation is unfavored and polymerization would proceed from existing nuclei such as the actomer.", "contents": "Polymerization of actin. V. A new organelle, the actomere, that initates the assembly of actin filaments in Thyone sperm. Between the acrosomal vacuole and the nucleus is a cup of amorphous material (profilactin) which is transformed into filaments during the acrosomal reaction. In the center of this cup in untreated Thyone sperm is a dense material which I refer to as the actomere; it is composed of 20-25 filaments embedded in a dense matrix. To visualize the substructure of the actomere, the profilactin around it must be removed. This is achieved either by demembranating the sperm with Triton X-100 and then raising the pH to 8.0, or by adding inophores to intact sperm at pH 8.0. Under these conditions, the actomere remains as a unit while the rest of the profilactin is solubilized or polymerized. When demembranated sperm are incubated under conditions in which the actin should polymerize, filaments grow from the end of the actomere: the actomere thus appears to behave as a nucleating body. This observation is strengthened by experiments in which untreated sperm are incubated in seawater or isotonic NaCl at pH 7.0 and the ionophore X537A is added; in this case, only a partial polymerization of the actin occurs and the acrosomal vacuole does not fuse with the cell surface. The actin filaments that do form, however, are attached to the apical end of the actomere. In fact, the elongating filaments push their way into and frequently through the acrosomal vacuole. Thus, it appears that the sperm organizes the actin filaments by controlling their nucleation. My model is that the cell controls the ammount of unbound actin such that it is slightly above the critical concentration for polymerization. Then, spontaneous nucleation is unfavored and polymerization would proceed from existing nuclei such as the actomer."}
{"id": "PMID:25903", "title": "The development of lysosomal apparatus. I. Lysosomal enzyme activities in the liver of mice at perinatal stages and those of their mothers.", "content": "The enzymatic activity of five acid hydrolases: acid phosphatase, arylsulfatase A, deoxyribonuclease, beta-glucuronidase, and cathepsin D, was assayed in fetal (fifteenth and eighteenth days of pregnancy) and neonatal (Days 0, 5, 10, and 15 post-partum) mouse liver. With the exception of cathepsin D, the activity increased around birth to levels varying according to the enzyme. Histochemical observations of other authors appear to justify, at least in part, the present results, which indicate that late days of fetal development and early neonatal life may constitute a transitional stage to full lysosomal enzyme functionality of the adult organ. The livers of the mothers were also assayed for the same enzymes. Each activity showed a peculiar pattern which was, in turn, different from that found in the liver of the litter for the same enzyme, probably as a cause of the metabolic requirement of the gland. The hypothesis that the lysosomes are heterogeneous in their enzyme composition is suggested by the variety of enzymatic patterns found in the liver of the litters and their mothers.", "contents": "The development of lysosomal apparatus. I. Lysosomal enzyme activities in the liver of mice at perinatal stages and those of their mothers. The enzymatic activity of five acid hydrolases: acid phosphatase, arylsulfatase A, deoxyribonuclease, beta-glucuronidase, and cathepsin D, was assayed in fetal (fifteenth and eighteenth days of pregnancy) and neonatal (Days 0, 5, 10, and 15 post-partum) mouse liver. With the exception of cathepsin D, the activity increased around birth to levels varying according to the enzyme. Histochemical observations of other authors appear to justify, at least in part, the present results, which indicate that late days of fetal development and early neonatal life may constitute a transitional stage to full lysosomal enzyme functionality of the adult organ. The livers of the mothers were also assayed for the same enzymes. Each activity showed a peculiar pattern which was, in turn, different from that found in the liver of the litter for the same enzyme, probably as a cause of the metabolic requirement of the gland. The hypothesis that the lysosomes are heterogeneous in their enzyme composition is suggested by the variety of enzymatic patterns found in the liver of the litters and their mothers."}
{"id": "PMID:25904", "title": "PH oscillations in cell suspensions of Dictyostelium discoideum: their relation to cyclic-amp signals.", "content": "Cells of Dictyostelium discoideum known to release cyclic AMP (cAMP) rhythmically in the form of pulses, change with the same period of about 8 min the pH of their medium. The pH is used here as an indicator to investigate the effect of externally added cAMP pulses on the oscillations. Both a temporary increase in amplitude and a permanent phase shift can be induced. The phase-response curve indicates that the period can be increased and decreased by rhythmic stimulation with cAMP pulses.", "contents": "PH oscillations in cell suspensions of Dictyostelium discoideum: their relation to cyclic-amp signals. Cells of Dictyostelium discoideum known to release cyclic AMP (cAMP) rhythmically in the form of pulses, change with the same period of about 8 min the pH of their medium. The pH is used here as an indicator to investigate the effect of externally added cAMP pulses on the oscillations. Both a temporary increase in amplitude and a permanent phase shift can be induced. The phase-response curve indicates that the period can be increased and decreased by rhythmic stimulation with cAMP pulses."}
{"id": "PMID:25909", "title": "Interpatient microbiological cross-contamination after dental radiographic examination.", "content": "Pairs of patients were evaluated for microbiological cross-contamination after radiographic examination. In 30 of these pairs of patients there was the possibility of transference of S pyogenes, S aureus, or D pneumoniae. Such transference was observed in 23 (77%) of these 30 pairs of patients. The vectors for such transfer include the hands of the X-ray technician and the radiographic equipment. Further, it was found that each of these organisms would survive for at least 48 hours after being placed on an X-ray tube. Since interpatient microbiological cross-contamination can occur after routine radiographic examination, in some cases, disinfection of the radiographic equipment is indicated.", "contents": "Interpatient microbiological cross-contamination after dental radiographic examination. Pairs of patients were evaluated for microbiological cross-contamination after radiographic examination. In 30 of these pairs of patients there was the possibility of transference of S pyogenes, S aureus, or D pneumoniae. Such transference was observed in 23 (77%) of these 30 pairs of patients. The vectors for such transfer include the hands of the X-ray technician and the radiographic equipment. Further, it was found that each of these organisms would survive for at least 48 hours after being placed on an X-ray tube. Since interpatient microbiological cross-contamination can occur after routine radiographic examination, in some cases, disinfection of the radiographic equipment is indicated."}
{"id": "PMID:25910", "title": "Tear pH: how predictable?", "content": "While the tear pH of a patient is now known to be continually shifting throughout the waking day, such variations were found to be contained within fairly narrow limits (a range here of about 0.6 of a pH unit). Further, sufficient repetition of these shifts occurred over 10 days observed that patterns distinctive of the individual patient often emerged.", "contents": "Tear pH: how predictable? While the tear pH of a patient is now known to be continually shifting throughout the waking day, such variations were found to be contained within fairly narrow limits (a range here of about 0.6 of a pH unit). Further, sufficient repetition of these shifts occurred over 10 days observed that patterns distinctive of the individual patient often emerged."}
{"id": "PMID:25934", "title": "A novel immunoadsorbent: use for the preparation of monospecific antibodies to the hepatitis B antigen.", "content": "Controlled pore glass (CPG) adsorbs hepatitis B surface antigen (HBsAg) from whole plasma with a high degree of specificity. The resultant complex is stable at acid pH and in the presence of high concentrations of sodium thiocyanate. The adsorbed HBsAg is qualitatively and quantitatively similar to the soluble material in its ability to bind antibodies to HBsAg (anti-HBs). The HBsAg in 1 ml of strongly reactive plasma is adsorbed by 100 mg of CPG, which can then specifically bind 32,000 passive hemagglutination units of anti-HBs. Bound antibody can be eluted in 77% yield by acid or by chaotropic ions and the CPG-HBsAg complex can be reused in further adsorption-elution cycles. Antibody to HBsAg can be purified 144-fold in a single step by using this technique. The preparation of monospecific subtyping reagents for HBsAg and of immunochemically purified anti-HBs is described.", "contents": "A novel immunoadsorbent: use for the preparation of monospecific antibodies to the hepatitis B antigen. Controlled pore glass (CPG) adsorbs hepatitis B surface antigen (HBsAg) from whole plasma with a high degree of specificity. The resultant complex is stable at acid pH and in the presence of high concentrations of sodium thiocyanate. The adsorbed HBsAg is qualitatively and quantitatively similar to the soluble material in its ability to bind antibodies to HBsAg (anti-HBs). The HBsAg in 1 ml of strongly reactive plasma is adsorbed by 100 mg of CPG, which can then specifically bind 32,000 passive hemagglutination units of anti-HBs. Bound antibody can be eluted in 77% yield by acid or by chaotropic ions and the CPG-HBsAg complex can be reused in further adsorption-elution cycles. Antibody to HBsAg can be purified 144-fold in a single step by using this technique. The preparation of monospecific subtyping reagents for HBsAg and of immunochemically purified anti-HBs is described."}
{"id": "PMID:25935", "title": "Sphingomyelinase in pig and human epidermis.", "content": "The enzyme sphingomyelinase (sphingomyelin phosphorylcholine phosphohydrolase E.C.3.1.4.12) which hydrolyzes sphingomyelin to ceramide (N-acylsphingosine) and phosphorylcholine was identified in the subcellular fractions of pig and human epidermis. The enzyme has an optimum pH of 4.5 to 5 and is activated by Triton X-100 (0.1% w/v). Approximately two-thirds of the enzyme activity in both the pig and human epidermal homogenates was in the soluble subcellular fraction and more than half of the enzyme activity in the subcellular particulate fraction was solubilized by freeze-thawing. The pH optimum suggests that epidermal sphingomyelinase is probably a lysozomal enzyme. The enzymes in both pig and human epidermis exhibited Michaelis-Menten kinetics. The soluble sphingomyelinase in pig epidermis had an apparent Km, 4.5 X 10(-5) M and that in human epidermis an apparent Km 7.7 X 10(-5) M. The pig epidermal sphingomyelinase had no special requirement for either divalent or heavy metal ions and was not inhibited by sulfydryl group-blocking agents but it was moderately inhibited by dithiothreitol. No evidence was found in either pig or human epidermis for the presence of a phospholipase C (E.C.3.1.4.3) which hydrolyzes phosphatidylcholine to diglyceride and phosphorylcholine but there was suggestive evidence of another catabolic pathway for phosphatidylcholine.", "contents": "Sphingomyelinase in pig and human epidermis. The enzyme sphingomyelinase (sphingomyelin phosphorylcholine phosphohydrolase E.C.3.1.4.12) which hydrolyzes sphingomyelin to ceramide (N-acylsphingosine) and phosphorylcholine was identified in the subcellular fractions of pig and human epidermis. The enzyme has an optimum pH of 4.5 to 5 and is activated by Triton X-100 (0.1% w/v). Approximately two-thirds of the enzyme activity in both the pig and human epidermal homogenates was in the soluble subcellular fraction and more than half of the enzyme activity in the subcellular particulate fraction was solubilized by freeze-thawing. The pH optimum suggests that epidermal sphingomyelinase is probably a lysozomal enzyme. The enzymes in both pig and human epidermis exhibited Michaelis-Menten kinetics. The soluble sphingomyelinase in pig epidermis had an apparent Km, 4.5 X 10(-5) M and that in human epidermis an apparent Km 7.7 X 10(-5) M. The pig epidermal sphingomyelinase had no special requirement for either divalent or heavy metal ions and was not inhibited by sulfydryl group-blocking agents but it was moderately inhibited by dithiothreitol. No evidence was found in either pig or human epidermis for the presence of a phospholipase C (E.C.3.1.4.3) which hydrolyzes phosphatidylcholine to diglyceride and phosphorylcholine but there was suggestive evidence of another catabolic pathway for phosphatidylcholine."}
{"id": "PMID:25938", "title": "Collecting duct hydrogen ion secretion in the rabbit: role of potassium.", "content": "The purpose of this study was to investigate distal nephron hydrogen ion secretion in the intact animal. The rabbit was chosen as the experimental model because it produces acid urine containing little ammonium. Upon replacement of the usual rabbit diet with milk, plus administration of an acid load (10 mEq/kg), the urine pH fell consistently from very alkaline values (PH greater than 7.4) to 4.8 +/- 0.2. Despite the ability to achieve high urine-to-blood hydrogen ion concentration gradients, the U-B PCO2, an index of collecting duct hydrogen ion secretion, was virtually zero. In these studies, the urine bicarbonate and buffer concentration were comparable to those observed in dog, rat, and man in which a high U-B PCO2 gradient was achieved. The rabbits studied had low plasma potassium concentrations (less than 3 mEq/L). Since potassium deficiency has been implicated in impaired urine acidification, potassium was administered, and it resulted in an increase in collecting duct hydrogen ion secretion as evidenced by a further fall in minimum urine pH during acidemia and a prompt rise in the U-B PCO2 during alkali administration. In summary, rabbits had a very low but not absent rate of collecting duct hydrogen ion secretion. Potassium administration increased the rate of hydrogen ion secretion in a segment of the collecting duct in which hydrogen ion secretion is reflected by an increase U-B PCO2.", "contents": "Collecting duct hydrogen ion secretion in the rabbit: role of potassium. The purpose of this study was to investigate distal nephron hydrogen ion secretion in the intact animal. The rabbit was chosen as the experimental model because it produces acid urine containing little ammonium. Upon replacement of the usual rabbit diet with milk, plus administration of an acid load (10 mEq/kg), the urine pH fell consistently from very alkaline values (PH greater than 7.4) to 4.8 +/- 0.2. Despite the ability to achieve high urine-to-blood hydrogen ion concentration gradients, the U-B PCO2, an index of collecting duct hydrogen ion secretion, was virtually zero. In these studies, the urine bicarbonate and buffer concentration were comparable to those observed in dog, rat, and man in which a high U-B PCO2 gradient was achieved. The rabbits studied had low plasma potassium concentrations (less than 3 mEq/L). Since potassium deficiency has been implicated in impaired urine acidification, potassium was administered, and it resulted in an increase in collecting duct hydrogen ion secretion as evidenced by a further fall in minimum urine pH during acidemia and a prompt rise in the U-B PCO2 during alkali administration. In summary, rabbits had a very low but not absent rate of collecting duct hydrogen ion secretion. Potassium administration increased the rate of hydrogen ion secretion in a segment of the collecting duct in which hydrogen ion secretion is reflected by an increase U-B PCO2."}
{"id": "PMID:25939", "title": "The distribution of bumps in the tail of the locust photoreceptor afterpotential.", "content": "An extended tail or prolonged depolarizing afterpotential (PDA) follows the receptor potential of a locust retinula cell when the stimulating light is in the intensity range that saturates the receptor potential. The amplitude and duration of this afterpotential depend on the intensity and duration of the stimulus. As the afterpotential decays, apparently exponentially, it becomes resolved into bumps, which we call light-induced dark bumps (LID bumps). The intervals between light-induced dark bumps are distributed in a way that is indistinguishable from a random (Poisson) distribution. As previously demonstrated, LID bumps are indistinguishable from bumps directly induced by low intensity light in light-adapted cells, which in turn grade into the slightly larger bumps produced, each by a single photon, in dark-adapted cells. The light-induced dark bumps continue for up to an hour in darkness, slowly becoming like dark-adapted bumps in amplitude and shape. To account for the random occurrence and discrete features of bumps after so long a latency, we propose that intense light generates a significant amount of an intermediate molecule or packet which decays slowly to start the same process that normally generates bumps with a short delay.", "contents": "The distribution of bumps in the tail of the locust photoreceptor afterpotential. An extended tail or prolonged depolarizing afterpotential (PDA) follows the receptor potential of a locust retinula cell when the stimulating light is in the intensity range that saturates the receptor potential. The amplitude and duration of this afterpotential depend on the intensity and duration of the stimulus. As the afterpotential decays, apparently exponentially, it becomes resolved into bumps, which we call light-induced dark bumps (LID bumps). The intervals between light-induced dark bumps are distributed in a way that is indistinguishable from a random (Poisson) distribution. As previously demonstrated, LID bumps are indistinguishable from bumps directly induced by low intensity light in light-adapted cells, which in turn grade into the slightly larger bumps produced, each by a single photon, in dark-adapted cells. The light-induced dark bumps continue for up to an hour in darkness, slowly becoming like dark-adapted bumps in amplitude and shape. To account for the random occurrence and discrete features of bumps after so long a latency, we propose that intense light generates a significant amount of an intermediate molecule or packet which decays slowly to start the same process that normally generates bumps with a short delay."}
{"id": "PMID:25940", "title": "Some responses of the electric ray (Torpedo marmorata) to low ambient oxygen tensions.", "content": "I. Blood samples were taken during prolonged hypoxia experiments in which the inspired water oxygen tension was less than 10 mmHg. The oxygen tension of the post-branchial blood was about 5 mmHg and its pH shows a significant lowering from normoxic levels. 2. The decrease in blood pH is correlated with increases in levels of lactate and pyruvate. The lactate/pyruvate ratio increases during hypoxia. 3. An increase in blood succinate was also found, and strongly suggests the accumulation of multiple anaerobic end-products within the tissues. 4. Recovery of normoxic levels of succinate takes place almost immediately following the restart of ventilation whereas the decrease in lactate concentration is slower. 5. It is concluded that these adaptations may be related to the habitat of the fish at low tide in pools where the Po2 may fall very markedly.", "contents": "Some responses of the electric ray (Torpedo marmorata) to low ambient oxygen tensions. I. Blood samples were taken during prolonged hypoxia experiments in which the inspired water oxygen tension was less than 10 mmHg. The oxygen tension of the post-branchial blood was about 5 mmHg and its pH shows a significant lowering from normoxic levels. 2. The decrease in blood pH is correlated with increases in levels of lactate and pyruvate. The lactate/pyruvate ratio increases during hypoxia. 3. An increase in blood succinate was also found, and strongly suggests the accumulation of multiple anaerobic end-products within the tissues. 4. Recovery of normoxic levels of succinate takes place almost immediately following the restart of ventilation whereas the decrease in lactate concentration is slower. 5. It is concluded that these adaptations may be related to the habitat of the fish at low tide in pools where the Po2 may fall very markedly."}
{"id": "PMID:25941", "title": "The identification of an octopaminergic neurone and the modulation of a myogenic rhythm in the locust.", "content": "An octopaminergic neurone in an insect is demonstrated. This cell (DUMETi) is the dorsal unpaired median neurone which projects to the extensor tibiae muscle of the locust metathoracic leg. Its soma was physiologically identified, isolated and shown to contain about 0.1 pmol of octopamine. Octopamine is about four times more concentrated in the axon than in the soma. The concentration in the soma is at least 800 times more than that in the soma of an identified motoneurone (which controls the fast extensor of the tibia). The effects of DUMETi on a myogenic rhythm in the extensor muscle of the locust metathoracic leg can be mimicked by superfusion with low concentrations of octopamine. The myogenic bundle possesses at least two types of aminergic receptor: one which slows the rhythm (and has a high-affinity for octopamine) and a second which accelerates the rhythm (and has a low-affinity for octopamine but a high-affinity for the indolalkylamine, 5-hydroxytryptamine). The roles of the two receptor types in modulating the rhythm are discussed in relation to the function of the rhythm.", "contents": "The identification of an octopaminergic neurone and the modulation of a myogenic rhythm in the locust. An octopaminergic neurone in an insect is demonstrated. This cell (DUMETi) is the dorsal unpaired median neurone which projects to the extensor tibiae muscle of the locust metathoracic leg. Its soma was physiologically identified, isolated and shown to contain about 0.1 pmol of octopamine. Octopamine is about four times more concentrated in the axon than in the soma. The concentration in the soma is at least 800 times more than that in the soma of an identified motoneurone (which controls the fast extensor of the tibia). The effects of DUMETi on a myogenic rhythm in the extensor muscle of the locust metathoracic leg can be mimicked by superfusion with low concentrations of octopamine. The myogenic bundle possesses at least two types of aminergic receptor: one which slows the rhythm (and has a high-affinity for octopamine) and a second which accelerates the rhythm (and has a low-affinity for octopamine but a high-affinity for the indolalkylamine, 5-hydroxytryptamine). The roles of the two receptor types in modulating the rhythm are discussed in relation to the function of the rhythm."}
{"id": "PMID:25942", "title": "Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.", "content": "Bone marrow (BM) and skin allografts from C57BL/Ka (H-2b/b) mice were transplanted to BALB/c (H-2d/d) recipients treated with total lymphoid irradiation (TLI), whole-body irradiation (WBI), or fractionated thymic irradiation TLI prolonged skin allograft survival about five times as long as that in untreated controls, and allowed for permanent engraftment of BM cells in approximately equal to 90% of recipients. None of the BM recipients showed clinical signs of graft-versus-host disease (GVHD) (diarrhea, weight loss, hunched back, etc.). On the other hand, recipients given WBI and allogeneic BM cells developed severe clinical GVHD. The majority of the latter recipients died within 12 days after BM transplantation, and 95% died within 61 days. Although TLI protected BALB/c mice against GVHD induced by BM cells, all recipients given TLI and allogeneic spleen cells developed lethal GVHD. Thymic irradiation alone marginally prolonged skin allograft survival, and did not allow for allogeneic BM engraftment. These results suggest that TLI may be a useful regimen in clinical BM transplantation, since this form of radiotherapy is used extensively in humans and has few severe side effects.", "contents": "Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation. Bone marrow (BM) and skin allografts from C57BL/Ka (H-2b/b) mice were transplanted to BALB/c (H-2d/d) recipients treated with total lymphoid irradiation (TLI), whole-body irradiation (WBI), or fractionated thymic irradiation TLI prolonged skin allograft survival about five times as long as that in untreated controls, and allowed for permanent engraftment of BM cells in approximately equal to 90% of recipients. None of the BM recipients showed clinical signs of graft-versus-host disease (GVHD) (diarrhea, weight loss, hunched back, etc.). On the other hand, recipients given WBI and allogeneic BM cells developed severe clinical GVHD. The majority of the latter recipients died within 12 days after BM transplantation, and 95% died within 61 days. Although TLI protected BALB/c mice against GVHD induced by BM cells, all recipients given TLI and allogeneic spleen cells developed lethal GVHD. Thymic irradiation alone marginally prolonged skin allograft survival, and did not allow for allogeneic BM engraftment. These results suggest that TLI may be a useful regimen in clinical BM transplantation, since this form of radiotherapy is used extensively in humans and has few severe side effects."}
{"id": "PMID:25943", "title": "Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.", "content": "Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.", "contents": "Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging. Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function."}
{"id": "PMID:25944", "title": "A comparative study of the electrode systems of three pH and blood gas apparatus.", "content": "We present a comparative evaluation of the electrode systems of three modern blood gas analysers: IL-413, ABL-1 and AVL-937C. The response curves, accuracy and precision of the pH-, pCO2- and pO2-electrodes were established with tonometered blood and buffer solutions. pH values (range 6.8-7.8) measured on the AVL deviate (-0.03 pH for blood and +0.03 pH for buffer) from those of BMS2 Mk2; whereas on the IL and ABL analysers the pH values deviate by not more than 0.01 pH. The standard deviation was better than 0.005 pH. pCO2 values of blood and buffer (range 14-106 mm Hg) deviate from the calculated tonometer values by quantities ranging from 3 to 10 mm Hg. The average precision (CV)1) of the pCO2 measurement on each analyser was better than 1.8%. pO2 values of blood (range 0-130 mm Hg) did not differ by more than 3 mm Hg from the calculated values. Above 130 mm Hg a linear negative increasing difference was seen. For buffer solutions a linear relationship between pO2 difference and pO2 value was found over the whole range from zero up to 642 mm Hg: a positive difference below and a negative difference above the pO2 of the previous calibration; if the calibration pO2 is higher, the sample pO2 is shifted to a higher value. The average precision of the pO2 measurements was better than 3%. In the (patho)-physiological range the three instruments may provide suitable results for the clinician. Suggestions are made for standardization and improvement of the electrode systems.", "contents": "A comparative study of the electrode systems of three pH and blood gas apparatus. We present a comparative evaluation of the electrode systems of three modern blood gas analysers: IL-413, ABL-1 and AVL-937C. The response curves, accuracy and precision of the pH-, pCO2- and pO2-electrodes were established with tonometered blood and buffer solutions. pH values (range 6.8-7.8) measured on the AVL deviate (-0.03 pH for blood and +0.03 pH for buffer) from those of BMS2 Mk2; whereas on the IL and ABL analysers the pH values deviate by not more than 0.01 pH. The standard deviation was better than 0.005 pH. pCO2 values of blood and buffer (range 14-106 mm Hg) deviate from the calculated tonometer values by quantities ranging from 3 to 10 mm Hg. The average precision (CV)1) of the pCO2 measurement on each analyser was better than 1.8%. pO2 values of blood (range 0-130 mm Hg) did not differ by more than 3 mm Hg from the calculated values. Above 130 mm Hg a linear negative increasing difference was seen. For buffer solutions a linear relationship between pO2 difference and pO2 value was found over the whole range from zero up to 642 mm Hg: a positive difference below and a negative difference above the pO2 of the previous calibration; if the calibration pO2 is higher, the sample pO2 is shifted to a higher value. The average precision of the pO2 measurements was better than 3%. In the (patho)-physiological range the three instruments may provide suitable results for the clinician. Suggestions are made for standardization and improvement of the electrode systems."}
{"id": "PMID:25946", "title": "Activation of rat pheochromocytoma tyrosine hydroxylase by a cyclic AMP-dependent protein kinase in a cell-free system.", "content": "Short term exposure of PC-12 cells to dibutyryl cyclic AMP (dB-cAMP) results in an activation of tyrosine hydroxylase. In the cell-free system the PC-12 tyrosine hydroxylase activity is stimulated by addition of c-AMP, Mg+2 and ATP. Exogenous c-AMP dependent protein kinase further stumulates tyrosine hydroxylase activity. The kinetic data suggests that the PC-12 tyrosine hydroxylase in the basal state is in a non-phosphorylated form but under phosphorylating conditions the enzyme is activated and its kinetics properties are altered.", "contents": "Activation of rat pheochromocytoma tyrosine hydroxylase by a cyclic AMP-dependent protein kinase in a cell-free system. Short term exposure of PC-12 cells to dibutyryl cyclic AMP (dB-cAMP) results in an activation of tyrosine hydroxylase. In the cell-free system the PC-12 tyrosine hydroxylase activity is stimulated by addition of c-AMP, Mg+2 and ATP. Exogenous c-AMP dependent protein kinase further stumulates tyrosine hydroxylase activity. The kinetic data suggests that the PC-12 tyrosine hydroxylase in the basal state is in a non-phosphorylated form but under phosphorylating conditions the enzyme is activated and its kinetics properties are altered."}
{"id": "PMID:25945", "title": "Intestinal transport of weak electrolytes: Determinants of influx at the luminal surface.", "content": "The determinants of weak electrolyte influx into everted segments of rat small intestine have been studied. Preliminary experiments showed that the observed influxes could be described as unidirectional, diffusional fluxes of the nonionized compound uncomplicated by a parallel ionic component. It is shown that the determinants of weak electrolyte influx in this situation may be described in terms of the resistance of the unstirred layer to movement from the bulk phase to the cell surface, the degree of ionization of the weak electrolyte at the cell surface, and the cellular permeability to the nonionized weak electrolyte. Quantitative considerations indicated that the unstirred layer was totally rate-limiting in the cases of some poorly ionized, or highly permeant compounds, but the unstirred layer was not totally rate limiting for most of the compounds studied. Calculation of cellular permeabilities for the nonionized forms of weak electrolytes required assumptions to be made concerning the pH value in the surface fluid layer. A uniform set of permeability data including both weak acids and weak bases was obtained only when it was assumed that the pH in the surface fluid layer was equal to that in the bulk phase, and it was concluded that these studies do not support the concept of a microclimate of distinctive pH at the epithelial surface as a determinant of weak electrolyte transport.", "contents": "Intestinal transport of weak electrolytes: Determinants of influx at the luminal surface. The determinants of weak electrolyte influx into everted segments of rat small intestine have been studied. Preliminary experiments showed that the observed influxes could be described as unidirectional, diffusional fluxes of the nonionized compound uncomplicated by a parallel ionic component. It is shown that the determinants of weak electrolyte influx in this situation may be described in terms of the resistance of the unstirred layer to movement from the bulk phase to the cell surface, the degree of ionization of the weak electrolyte at the cell surface, and the cellular permeability to the nonionized weak electrolyte. Quantitative considerations indicated that the unstirred layer was totally rate-limiting in the cases of some poorly ionized, or highly permeant compounds, but the unstirred layer was not totally rate limiting for most of the compounds studied. Calculation of cellular permeabilities for the nonionized forms of weak electrolytes required assumptions to be made concerning the pH value in the surface fluid layer. A uniform set of permeability data including both weak acids and weak bases was obtained only when it was assumed that the pH in the surface fluid layer was equal to that in the bulk phase, and it was concluded that these studies do not support the concept of a microclimate of distinctive pH at the epithelial surface as a determinant of weak electrolyte transport."}
{"id": "PMID:25951", "title": "Double mode of action of black widow spider venom on frog neuromuscular junction.", "content": "Black widow spider venom (BWSV) contains a toxin, alpha-latrotoxin, which is capable of stimulating vesicle release, resulting eventually in depletion of vesicles and block of neuromuscular transmission at the frog neuromuscular junction. Since it has been shown that alpha-latrotoxin very markedly increases the cation conductance of artificial lipid bilayers, it was postulated that BWSV stimulates release by opening channels permeable to Ca2+ and, in the case of Ca2+-free Ringer's, to Na+ which would release Ca2+ from intracellular stores. To test this hypothesis we chose as a sodium substitute, glucosamine, which is impermeable to the venom-induced channels in the lipid bilayers and to the postsynaptic membrane of the frog neuromuscular junction. Electron microscopical analysis showed that up to 75 min perfusion in Na+ and Ca2+-free medium did not alter the ultrastructure of the nerve terminals. However when BWSV was applied in this medium a significant depletion was noticeable within 15 min and after 60 min the terminals were depleted of vesicles whereas the mitochondria were unchanged in number and structure. If BWSV is applied for 60 min in glucosamine Ringer's containing 1.8 mM Ca2+, most of the nerve terminals still have synaptic vesicles scattered in the cytoplasm or clustered around amorphous structures and the mitochondria are swollen. Application of large doses of BWSV in low Ca2+ Ringer's leads to damage of the mitochondria and to very pronounced swelling of the nerve endings, whereas this is not observed if the dose of venom is applied in Na+-free and Ca2+-free Ringer's. Electrophysiological recording showed that neuromuscular transmission is already blocked after 15 min treatment with BWSV in glucosamine-Ringer's. From these results we conclude that BWSV increases the conductance of the nerve terminal membrane to cations such as Na+ and Ca2+ and stimulates release by a mechanism which may not involve its ionophore property.", "contents": "Double mode of action of black widow spider venom on frog neuromuscular junction. Black widow spider venom (BWSV) contains a toxin, alpha-latrotoxin, which is capable of stimulating vesicle release, resulting eventually in depletion of vesicles and block of neuromuscular transmission at the frog neuromuscular junction. Since it has been shown that alpha-latrotoxin very markedly increases the cation conductance of artificial lipid bilayers, it was postulated that BWSV stimulates release by opening channels permeable to Ca2+ and, in the case of Ca2+-free Ringer's, to Na+ which would release Ca2+ from intracellular stores. To test this hypothesis we chose as a sodium substitute, glucosamine, which is impermeable to the venom-induced channels in the lipid bilayers and to the postsynaptic membrane of the frog neuromuscular junction. Electron microscopical analysis showed that up to 75 min perfusion in Na+ and Ca2+-free medium did not alter the ultrastructure of the nerve terminals. However when BWSV was applied in this medium a significant depletion was noticeable within 15 min and after 60 min the terminals were depleted of vesicles whereas the mitochondria were unchanged in number and structure. If BWSV is applied for 60 min in glucosamine Ringer's containing 1.8 mM Ca2+, most of the nerve terminals still have synaptic vesicles scattered in the cytoplasm or clustered around amorphous structures and the mitochondria are swollen. Application of large doses of BWSV in low Ca2+ Ringer's leads to damage of the mitochondria and to very pronounced swelling of the nerve endings, whereas this is not observed if the dose of venom is applied in Na+-free and Ca2+-free Ringer's. Electrophysiological recording showed that neuromuscular transmission is already blocked after 15 min treatment with BWSV in glucosamine-Ringer's. From these results we conclude that BWSV increases the conductance of the nerve terminal membrane to cations such as Na+ and Ca2+ and stimulates release by a mechanism which may not involve its ionophore property."}
{"id": "PMID:25954", "title": "N-Halo derivatives V: Comparative antimicrobial activity of soft N-chloramine systems.", "content": "Comparative antimicrobial activity studies for certain new classes of soft N-chloramines derived from alpha-aminiisobutyric acid and 2-amino-2-methyl-1-propanol were examined using the minimum inhibitory concentration (MIC) and/or the contact germicidal efficiency (CGE) procedures. Several factors significantly aliphatic chain length in a homologous series, (b) the degree of chlorination of thenitrogen atom, (c) the solution pH, (d) the presence of a denaturant, and (e) the nature of a positive charge.", "contents": "N-Halo derivatives V: Comparative antimicrobial activity of soft N-chloramine systems. Comparative antimicrobial activity studies for certain new classes of soft N-chloramines derived from alpha-aminiisobutyric acid and 2-amino-2-methyl-1-propanol were examined using the minimum inhibitory concentration (MIC) and/or the contact germicidal efficiency (CGE) procedures. Several factors significantly aliphatic chain length in a homologous series, (b) the degree of chlorination of thenitrogen atom, (c) the solution pH, (d) the presence of a denaturant, and (e) the nature of a positive charge."}
{"id": "PMID:25955", "title": "Stability of aqueous solutions of mibolerone.", "content": "The kinetics and mechanism of degradation of mibolerone were studied in aqueous buffered solutions in the pH range of 1-8 at 67.5 degrees. Mibolerone showed maximum stability between pH 5.5 and 6.4. At pH 1-2, the major degradative pathway was dehydration followed by migration of the 18-methyl group to form 7alpha,17,17-trimethylgona-4,13-dien-3-one. While there was only one degradation product at pH 1-2, the degradation at pH 7-8 was complex. As many as 12 degradation products were detected by GLC. Mass spectral data indicated that the majority of these products were either oxidation products or isomers. At pH 7.6, the apparent first-order rate constants exhibited marked dependency on buffer concentration. Incorporation of a sequestering agent into the solutions eliminated this dependency, suggesting that trace metal impurities from the buffer reagents were catalyzing the degradation. This was confirmed by degradation studies of solutions in water for injection containing 5 ppm of trace metal ions. Sn+2, Cu\"2, and Fe+2 accelerated the degradation, with Fe+2 having the most catalytic effect. The temperature dependence of the rate of degradation was studied in 0.05 M phosphate buffer at pH 6.4. The activation energy was 19.6 +/- 1.63 kcal/mole.", "contents": "Stability of aqueous solutions of mibolerone. The kinetics and mechanism of degradation of mibolerone were studied in aqueous buffered solutions in the pH range of 1-8 at 67.5 degrees. Mibolerone showed maximum stability between pH 5.5 and 6.4. At pH 1-2, the major degradative pathway was dehydration followed by migration of the 18-methyl group to form 7alpha,17,17-trimethylgona-4,13-dien-3-one. While there was only one degradation product at pH 1-2, the degradation at pH 7-8 was complex. As many as 12 degradation products were detected by GLC. Mass spectral data indicated that the majority of these products were either oxidation products or isomers. At pH 7.6, the apparent first-order rate constants exhibited marked dependency on buffer concentration. Incorporation of a sequestering agent into the solutions eliminated this dependency, suggesting that trace metal impurities from the buffer reagents were catalyzing the degradation. This was confirmed by degradation studies of solutions in water for injection containing 5 ppm of trace metal ions. Sn+2, Cu\"2, and Fe+2 accelerated the degradation, with Fe+2 having the most catalytic effect. The temperature dependence of the rate of degradation was studied in 0.05 M phosphate buffer at pH 6.4. The activation energy was 19.6 +/- 1.63 kcal/mole."}
{"id": "PMID:25957", "title": "Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles.", "content": "1. The effects of decreasing pH from 7.40 to 6.20 on the tension developed by direct activation of the myofilaments and by Ca2+ release from the sarcoplasmic reticulum were studied comparatively in segments of single cells of skeletal muscle (frog semitendinosus) and cardiac muscle (rat ventricle) from which the sarcolemma had been removed by micro-dissection (skinned muscle cells). 2. The concentration of free Ca2+ in the solutions was buffered with ethylene glycol-bis (beta-aminoethylether N,N'-tetraacetic acid (EGTA). The change of the buffer capacity of a given [total EGTA] caused by varying pH and the uncertainty about the value of the equilibrium constant for Ca-EGTA have been taken into account in the interpretation of the results. 3. Decreasing pH from 7.40 to 6.20 produced an increase in the [free Ca2+] required for the myofilaments to develop 50% of the maximum tension by a factor of about 5 in skinned cardiac cells but of only 3 in skeletal muscle fibres. In addition, acidosis depressed the maximum tension developed in the presence of a saturating [free Ca2+] by approximately the same amount in the two tissues. 4. The pH optimum for loading the sarcoplasmic reticulum of skinned fibres from skeletal muscle decreased when the pCa (-log [free Ca2+]) in the loading solution decreased. The optimum was pH 7.40-7.00 for a loading at pCa 7.75, pH 7.00-6.60 at pCa 7.00 and pH 6.60-6.20 at pCa 6.00. 5. The pH optimum for loading the sarcoplasmic reticulum of skinned cardiac cells with a solution at pCa 7.75 was about pH 7.40 as in skeletal muscle fibres. But the cardiac sarcoplasmic reticulum could not be loaded with a [free Ca2+] much higher than pCa 7.75 because a higher [free Ca2+] triggered a Ca2+-induced release of Ca2+ from the sarcoplasmic reticulum. 6. The pH optimum of about 7.40 for the loading of the cardiac sarcoplasmic reticulum was also optimum for the Ca2+-induced release of Ca2+ from it. 7. It was concluded that the effects of acidosis on the cardiac sarcoplasmic reticulum accentuate the depressive action of decreasing pH on the myofilaments. This may explain the pronounced depression of contractility observed during acidosis in cardiac muscle. In contrast, a moderate acidosis causes an effect on skeletal muscle sarcoplasmic reticulum that could compensate for the depressive action on the myofilaments, which is, in addition, less pronounced than in cardiac muscle.", "contents": "Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. 1. The effects of decreasing pH from 7.40 to 6.20 on the tension developed by direct activation of the myofilaments and by Ca2+ release from the sarcoplasmic reticulum were studied comparatively in segments of single cells of skeletal muscle (frog semitendinosus) and cardiac muscle (rat ventricle) from which the sarcolemma had been removed by micro-dissection (skinned muscle cells). 2. The concentration of free Ca2+ in the solutions was buffered with ethylene glycol-bis (beta-aminoethylether N,N'-tetraacetic acid (EGTA). The change of the buffer capacity of a given [total EGTA] caused by varying pH and the uncertainty about the value of the equilibrium constant for Ca-EGTA have been taken into account in the interpretation of the results. 3. Decreasing pH from 7.40 to 6.20 produced an increase in the [free Ca2+] required for the myofilaments to develop 50% of the maximum tension by a factor of about 5 in skinned cardiac cells but of only 3 in skeletal muscle fibres. In addition, acidosis depressed the maximum tension developed in the presence of a saturating [free Ca2+] by approximately the same amount in the two tissues. 4. The pH optimum for loading the sarcoplasmic reticulum of skinned fibres from skeletal muscle decreased when the pCa (-log [free Ca2+]) in the loading solution decreased. The optimum was pH 7.40-7.00 for a loading at pCa 7.75, pH 7.00-6.60 at pCa 7.00 and pH 6.60-6.20 at pCa 6.00. 5. The pH optimum for loading the sarcoplasmic reticulum of skinned cardiac cells with a solution at pCa 7.75 was about pH 7.40 as in skeletal muscle fibres. But the cardiac sarcoplasmic reticulum could not be loaded with a [free Ca2+] much higher than pCa 7.75 because a higher [free Ca2+] triggered a Ca2+-induced release of Ca2+ from the sarcoplasmic reticulum. 6. The pH optimum of about 7.40 for the loading of the cardiac sarcoplasmic reticulum was also optimum for the Ca2+-induced release of Ca2+ from it. 7. It was concluded that the effects of acidosis on the cardiac sarcoplasmic reticulum accentuate the depressive action of decreasing pH on the myofilaments. This may explain the pronounced depression of contractility observed during acidosis in cardiac muscle. In contrast, a moderate acidosis causes an effect on skeletal muscle sarcoplasmic reticulum that could compensate for the depressive action on the myofilaments, which is, in addition, less pronounced than in cardiac muscle."}
{"id": "PMID:25959", "title": "The effects of pH and curare on the time course of end-plate currents at the neuromuscular junction of the frog.", "content": "1. The effect of pH changes on synaptic currents has been analysed by external recording of the miniature end-plate currents (m.e.p.c.s) or by recording in voltage-clamped end-plates the current elicited by nerve stimulation (e.p.c.). 2. Changes in pH do not appreciably effect the peak amplitude of the current produced by a single quantum or by short ionophoretic pulses of acetylcholine. 3. The time constant of decay of the m.e.p.c.s is prolonged by about 50% in acid pH and shortened by about the same amount in alkaline pH. This effect is independent of the cholinesterase activity of the end-plate. 4. In curarized preparations the decay of the e.p.c. is shorter than in Mg-blocked end-plate even in the absence of cholinesterase blocking agents. 5. The action of pH on the decays can be explained by a titration of the surface charges of the membrane which effects the voltage dependent reaction that controls the rate of closing of the synaptic channels.", "contents": "The effects of pH and curare on the time course of end-plate currents at the neuromuscular junction of the frog. 1. The effect of pH changes on synaptic currents has been analysed by external recording of the miniature end-plate currents (m.e.p.c.s) or by recording in voltage-clamped end-plates the current elicited by nerve stimulation (e.p.c.). 2. Changes in pH do not appreciably effect the peak amplitude of the current produced by a single quantum or by short ionophoretic pulses of acetylcholine. 3. The time constant of decay of the m.e.p.c.s is prolonged by about 50% in acid pH and shortened by about the same amount in alkaline pH. This effect is independent of the cholinesterase activity of the end-plate. 4. In curarized preparations the decay of the e.p.c. is shorter than in Mg-blocked end-plate even in the absence of cholinesterase blocking agents. 5. The action of pH on the decays can be explained by a titration of the surface charges of the membrane which effects the voltage dependent reaction that controls the rate of closing of the synaptic channels."}
{"id": "PMID:25960", "title": "Effects of dithiothreitol on end-plate currents.", "content": "1. End-plate currents have been studied in frog cutaneus pectoris nerve-muscle preparations mounted in continuously flowing solution, using the voltage clamp technique. 2. Exposure of the muscle to 1 mM-dithiothreitol reduced the amplitude of end-plate currents by a factor of 2.7 (mean; range 1.6-3.4; twelve fibres). 3. 1 mM-dithiothreitol also caused a 2.7-fold (2.3-3.1) increase in the rate of decay, and a 1.4-fold (1.3-1.6) decrease in the time to peak of end-plate currents. During the onset of action of dithiothreitol, there was little or no indication of departure of end-plate current decay from a simple exponential. 4. Dithiothreitol actions on amplitude and decay of end-plate currents developed with similar time courses and both effects were slower in onset at pH 7.2 than at pH 8.5. 5. The actions of dithiothreitol were reversed by exposure of the muscle to 1 mM-5,5'-dithio-bis-(2-nitrobenzoic acid). 6. Following dithiothreitol treatment, the rates of decay of end-plate currents continued to depend on membrane potential; there was little or no change in the slope of the relation between in (rate of decay) and membrane potential, consistent with little or no change in the dipole moment of a gating molecule for ion channels. 7. Dithiothreitol changed the relation between peak end-plate current and membrane potential, so that peak conductance increased at more negative membrane potentials; this finding could be accounted for in terms of the closure of ion-channel gates becoming faster though remaining voltage-sensitive after exposure to dithiothreitol. 8. It is concluded that dithiothreitol causes changes in the kinetics of gating of ion channels associated with receptors and that these changes accompany changes in the binding of ACh to receptors.", "contents": "Effects of dithiothreitol on end-plate currents. 1. End-plate currents have been studied in frog cutaneus pectoris nerve-muscle preparations mounted in continuously flowing solution, using the voltage clamp technique. 2. Exposure of the muscle to 1 mM-dithiothreitol reduced the amplitude of end-plate currents by a factor of 2.7 (mean; range 1.6-3.4; twelve fibres). 3. 1 mM-dithiothreitol also caused a 2.7-fold (2.3-3.1) increase in the rate of decay, and a 1.4-fold (1.3-1.6) decrease in the time to peak of end-plate currents. During the onset of action of dithiothreitol, there was little or no indication of departure of end-plate current decay from a simple exponential. 4. Dithiothreitol actions on amplitude and decay of end-plate currents developed with similar time courses and both effects were slower in onset at pH 7.2 than at pH 8.5. 5. The actions of dithiothreitol were reversed by exposure of the muscle to 1 mM-5,5'-dithio-bis-(2-nitrobenzoic acid). 6. Following dithiothreitol treatment, the rates of decay of end-plate currents continued to depend on membrane potential; there was little or no change in the slope of the relation between in (rate of decay) and membrane potential, consistent with little or no change in the dipole moment of a gating molecule for ion channels. 7. Dithiothreitol changed the relation between peak end-plate current and membrane potential, so that peak conductance increased at more negative membrane potentials; this finding could be accounted for in terms of the closure of ion-channel gates becoming faster though remaining voltage-sensitive after exposure to dithiothreitol. 8. It is concluded that dithiothreitol causes changes in the kinetics of gating of ion channels associated with receptors and that these changes accompany changes in the binding of ACh to receptors."}
{"id": "PMID:25961", "title": "Anion transport of the red cell under non-equilibrium conditions.", "content": "1. The exchange of sulphate for chloride across the human red cell membrane was measured in both directions, i.e. by sulphate influx and sulphate efflux. The influence of the concomitant transient pH changes was minimized by phosphate buffer and by choosing experimental conditions of moderate pH sensitivity (pH 6.4 and 7.8). Sulphate self exchange was determined in chloride-free erythrocyte suspensions. 2. The transport of external sulphate into red cells proceeded at a 15-fold greater rate if its initial concentration was raised from 5 to 95 mM. In contrast the velocity constant of sulphate efflux into sodium chloride medium increased only twofold when the intracellular sulphate concentration was increased. To explain this asymmetry it is proposed that external sulphate ions are more able to complete with chloride for the anion transport sites that those present in the cell interior. 3. The transient membrane potential due to the uneven distribution of sulphate and chloride was shown by the rapid introduction of chromate into the cells. When the  erythrocytes contained chloride and the external anion was sulphate, the cells took up chromate 50 times (16.5 degrees C) faster than with equilibrium chloride distribution. 4. Chloride efflux into sodium sulphate media was measured by a chloride-sensitive electrode. Under buffered conditions in neutral and alkaline media two kinetic components were observed as the result of chloride exchange against hydroxyl and sulphate ions. At pH 6.4, chloride efflux was characterized by a single velocity constant identical to that of sulphate movement in the opposite direction. The results show that under appropriate circumstances net chloride efflux measurements can provide comparative data on the anion permeability of the red cell membrane.", "contents": "Anion transport of the red cell under non-equilibrium conditions. 1. The exchange of sulphate for chloride across the human red cell membrane was measured in both directions, i.e. by sulphate influx and sulphate efflux. The influence of the concomitant transient pH changes was minimized by phosphate buffer and by choosing experimental conditions of moderate pH sensitivity (pH 6.4 and 7.8). Sulphate self exchange was determined in chloride-free erythrocyte suspensions. 2. The transport of external sulphate into red cells proceeded at a 15-fold greater rate if its initial concentration was raised from 5 to 95 mM. In contrast the velocity constant of sulphate efflux into sodium chloride medium increased only twofold when the intracellular sulphate concentration was increased. To explain this asymmetry it is proposed that external sulphate ions are more able to complete with chloride for the anion transport sites that those present in the cell interior. 3. The transient membrane potential due to the uneven distribution of sulphate and chloride was shown by the rapid introduction of chromate into the cells. When the  erythrocytes contained chloride and the external anion was sulphate, the cells took up chromate 50 times (16.5 degrees C) faster than with equilibrium chloride distribution. 4. Chloride efflux into sodium sulphate media was measured by a chloride-sensitive electrode. Under buffered conditions in neutral and alkaline media two kinetic components were observed as the result of chloride exchange against hydroxyl and sulphate ions. At pH 6.4, chloride efflux was characterized by a single velocity constant identical to that of sulphate movement in the opposite direction. The results show that under appropriate circumstances net chloride efflux measurements can provide comparative data on the anion permeability of the red cell membrane."}
{"id": "PMID:25967", "title": "5-Chloro-2-phenyl-1-benzo[b]thiophene-3-alkanimines, potential antipsychotic agents.", "content": "The title compounds (most notably 2a) were synthesized on the basis of the N-methylation hypothesis of schizophrenia. They were evaluated in dopamine and haloperidol receptor assays. The binding characteristics were comparable in some cases to known neuroleptics.", "contents": "5-Chloro-2-phenyl-1-benzo[b]thiophene-3-alkanimines, potential antipsychotic agents. The title compounds (most notably 2a) were synthesized on the basis of the N-methylation hypothesis of schizophrenia. They were evaluated in dopamine and haloperidol receptor assays. The binding characteristics were comparable in some cases to known neuroleptics."}
{"id": "PMID:25968", "title": "Chemical and electrochemical oxidation of 7-hydroxychlorpromazine.", "content": "The oxidation of 7-hydroxychlorpromazine, a process associated with several side effects of chlorpromazine therapy, was examined in vitro by electrochemistry and rapid-scanning spectrophotometry. At pH 2, the oxidation results in a quantitative yield of 7,8-dioxochlorpromazine, but several intermediates are observable during the course of the reaction. These include a quinone imine with a half-life of 0.1 s, a monosubstituted benzoquinone with a half-life of approximately 50 s, and a disubstituted benzoquinone with a half-life of approximately 5 min. The concentrations of each intermediate were determined quantitatively as a function of time, and a complete oxidation mechanism is proposed. At pH 7, the yield of 7,8-dioxochlorpromazine is less than at pH 2, and an additional reaction pathway involving direct hydroxylation of the quinone imine is observed. The relationship of these reactions to the pharmacology of the hydroxylated chlorpromazine metabolites is discussed.", "contents": "Chemical and electrochemical oxidation of 7-hydroxychlorpromazine. The oxidation of 7-hydroxychlorpromazine, a process associated with several side effects of chlorpromazine therapy, was examined in vitro by electrochemistry and rapid-scanning spectrophotometry. At pH 2, the oxidation results in a quantitative yield of 7,8-dioxochlorpromazine, but several intermediates are observable during the course of the reaction. These include a quinone imine with a half-life of 0.1 s, a monosubstituted benzoquinone with a half-life of approximately 50 s, and a disubstituted benzoquinone with a half-life of approximately 5 min. The concentrations of each intermediate were determined quantitatively as a function of time, and a complete oxidation mechanism is proposed. At pH 7, the yield of 7,8-dioxochlorpromazine is less than at pH 2, and an additional reaction pathway involving direct hydroxylation of the quinone imine is observed. The relationship of these reactions to the pharmacology of the hydroxylated chlorpromazine metabolites is discussed."}
{"id": "PMID:25970", "title": "The incidence of mosquitoes feeding on mothers and babies at Kisumu, Kenya.", "content": "Blood fed mosquitoes were collected inside four bed nets in which mother/child pairs, having different haptoglobin types, slept. The bloodmeals were analysed by gradient gel electrophoresis to determine on which person the mosquitoes had fed. The results suggest that the mothers are fed on much more than babies by both Anopheles gambiae s.l. and Culex fatigans. In one hut at least 15.2 per cent of the mosquitoes had taken all or part of their bloodmeal elsewhere. A greater number of double feeds were detected from engorged Cx. fatigans (12.6%) than An. gambiae s.l. (2.7%).", "contents": "The incidence of mosquitoes feeding on mothers and babies at Kisumu, Kenya. Blood fed mosquitoes were collected inside four bed nets in which mother/child pairs, having different haptoglobin types, slept. The bloodmeals were analysed by gradient gel electrophoresis to determine on which person the mosquitoes had fed. The results suggest that the mothers are fed on much more than babies by both Anopheles gambiae s.l. and Culex fatigans. In one hut at least 15.2 per cent of the mosquitoes had taken all or part of their bloodmeal elsewhere. A greater number of double feeds were detected from engorged Cx. fatigans (12.6%) than An. gambiae s.l. (2.7%)."}
{"id": "PMID:25971", "title": "Experience with 425 subfertile male patients.", "content": "Subfertility was evaluated in 425 men. Varicocele were diagnosed in 37.4 per cent of these patients and surgical correction of the varicocele in 68 men resulted in a 65 per cent improvement in semen quality. Idiopathic abnormalities were found in 25.4 per cent of the patients. Since the study group was heterogenous setereotyped or empirical treatment cannot hope to be successful if uniformly applied. Other specific causes of male subfertility are identified and therapeutic options are discussed.", "contents": "Experience with 425 subfertile male patients. Subfertility was evaluated in 425 men. Varicocele were diagnosed in 37.4 per cent of these patients and surgical correction of the varicocele in 68 men resulted in a 65 per cent improvement in semen quality. Idiopathic abnormalities were found in 25.4 per cent of the patients. Since the study group was heterogenous setereotyped or empirical treatment cannot hope to be successful if uniformly applied. Other specific causes of male subfertility are identified and therapeutic options are discussed."}
{"id": "PMID:25973", "title": "Effects of K\u00f6 1366 on the hemodynamics of the normotensive and hypertensive elderly subjects.", "content": "The hemodynamic effects of a new adrenergic beta-receptor blocking agent, K\u00f6 1366 were investigated in normotensive and hypertensive elderly subjects. This study, in its important part, was carried out to clarify whether the intrinsic sympathomimetic activity of K\u00f6 1366 modified the hemodynamic changes due to beta-adrenergic blocking action or not. Hemodynamic changes elicited by intravenously administered K\u00f6 1366 (0.05 mg/Kg) were correlated with age, cardiac index, and electrocardiographic findings, respectively. With reference to age in normotensive subjects, K\u00f6 1366 caused no significant differences in rate of changes of various hemodynamic items between 3 age groups. Normotensive elderly subjects were divided into 3 groups according to cardic index. Cardiac index decreased greatly in high cardiac index group, slightly in normal cardiac index group, whereas it increased greatly in low cardiac index group. Stroke volume index showed the same tendency as cardiac index. Hypertensive elderly subjects were, also divided into 2 groups according to cardiac index. Again, cardiac index decreased in higher cardiac index group, while it increased in lower cardiac index group, though a statistical evaluation showed only a tendency of significant difference between 2 groups. In the next, hypertensive elderly subjects were divided into 2 groups according to electrocardiographic findings of left ventricular hypertrophy. Cardiac index decreased in the subjects without electrocardiographic changes, while it increased in the subjects with electrocardiographic changes. Stroke volume index of both groups increased: a greater increase in the subjects with electrocardiographic changes and a tendency of significant difference between 2 groups was recognized. These results suggested that K\u00f6 1366 exhibited the intrinsic symathomimetic activity on the inotropism in the hearts with depressed contractile function of both normotensive and hypertensive subjects, thereby canceling the negative chronotropic action of this agent. This could be a more advantageous point of K\u00f6 1366 in the treatment of elderly subjects with cardiac diseases than other agents without the intrinsic sympathomimetic activity.", "contents": "Effects of K\u00f6 1366 on the hemodynamics of the normotensive and hypertensive elderly subjects. The hemodynamic effects of a new adrenergic beta-receptor blocking agent, K\u00f6 1366 were investigated in normotensive and hypertensive elderly subjects. This study, in its important part, was carried out to clarify whether the intrinsic sympathomimetic activity of K\u00f6 1366 modified the hemodynamic changes due to beta-adrenergic blocking action or not. Hemodynamic changes elicited by intravenously administered K\u00f6 1366 (0.05 mg/Kg) were correlated with age, cardiac index, and electrocardiographic findings, respectively. With reference to age in normotensive subjects, K\u00f6 1366 caused no significant differences in rate of changes of various hemodynamic items between 3 age groups. Normotensive elderly subjects were divided into 3 groups according to cardic index. Cardiac index decreased greatly in high cardiac index group, slightly in normal cardiac index group, whereas it increased greatly in low cardiac index group. Stroke volume index showed the same tendency as cardiac index. Hypertensive elderly subjects were, also divided into 2 groups according to cardiac index. Again, cardiac index decreased in higher cardiac index group, while it increased in lower cardiac index group, though a statistical evaluation showed only a tendency of significant difference between 2 groups. In the next, hypertensive elderly subjects were divided into 2 groups according to electrocardiographic findings of left ventricular hypertrophy. Cardiac index decreased in the subjects without electrocardiographic changes, while it increased in the subjects with electrocardiographic changes. Stroke volume index of both groups increased: a greater increase in the subjects with electrocardiographic changes and a tendency of significant difference between 2 groups was recognized. These results suggested that K\u00f6 1366 exhibited the intrinsic symathomimetic activity on the inotropism in the hearts with depressed contractile function of both normotensive and hypertensive subjects, thereby canceling the negative chronotropic action of this agent. This could be a more advantageous point of K\u00f6 1366 in the treatment of elderly subjects with cardiac diseases than other agents without the intrinsic sympathomimetic activity."}
{"id": "PMID:25987", "title": "[Metabolic changes in the retina after experimental microembolism in the miniature pig (author's transl)].", "content": "Experimental microembolisation provokes hemodynamics and metabolic changes in the inner retina. The metabolic modifications are the consequence of focal tissue ischaemia and have as a main feature, the activation of anaerobic glycolysis. This activation produces an increase in the production of lactic acid which, in turn, causes a drop of tissular pH. Choroidal circulation maintains photoreceptors in a physiological state.", "contents": "[Metabolic changes in the retina after experimental microembolism in the miniature pig (author's transl)]. Experimental microembolisation provokes hemodynamics and metabolic changes in the inner retina. The metabolic modifications are the consequence of focal tissue ischaemia and have as a main feature, the activation of anaerobic glycolysis. This activation produces an increase in the production of lactic acid which, in turn, causes a drop of tissular pH. Choroidal circulation maintains photoreceptors in a physiological state."}
{"id": "PMID:26006", "title": "[Apparatus for the multichannel pH measurement of the upper section of the gastrointestinal tract].", "content": "To study simultaneously the acid-base processes in the esophagus, stomach and duodenum a procedure involving the use of multichannel pH measurements is proposed and a setup designed whose basic elements are a 6-channel pH-probe and a registering device. A visual and graphic registration of the investigation results is envisaged.", "contents": "[Apparatus for the multichannel pH measurement of the upper section of the gastrointestinal tract]. To study simultaneously the acid-base processes in the esophagus, stomach and duodenum a procedure involving the use of multichannel pH measurements is proposed and a setup designed whose basic elements are a 6-channel pH-probe and a registering device. A visual and graphic registration of the investigation results is envisaged."}
{"id": "PMID:26014", "title": "Tardive dyskinesia and antihistamines.", "content": "A case of tardive dyskinesia due to the prolonged administration of antihistamines is reported. Clinical features are discussed, as well as the alleviation of these by haloperidol.", "contents": "Tardive dyskinesia and antihistamines. A case of tardive dyskinesia due to the prolonged administration of antihistamines is reported. Clinical features are discussed, as well as the alleviation of these by haloperidol."}
{"id": "PMID:26015", "title": "Labetalol in the treatment of hypertensive renal patients.", "content": "The efficacy of labetalol in lowering blood pressure was assessed in 18 patients with chronic renal failure and hypertension. Before the start of labetalol therapy, all patients were receiving combined antihypertensive therapy, the most common being a beta-blocker and hydrallazine. Over the period of about four weeks labetalol was substituted for the prior therapy. 51Cr edetic acid (EDTA) estimations of glomerular filtration rate were performed before labetalol therapy, and then again after one and six months. Before the therapy with labetalol, 12 of the 18 patients had supine diastolic blood pressures of 100 mm Hg or more. At six months, 14 patients remained in the trial and, of these, only four had a supine diastolic blood pressure of 100 mm Hg or more. In the supine position there was a significant reduction of systolic, but not of diastolic, blood pressure. However, in the erect position there was a significant reduction both in systolic and in diastolic blood presure. Pulse rate did not vary significantly. Few side effects were encountered, transient postural dizziness being the most common side effect. Labetalol seems to be an effective substitute for the beta-blocker plus hydrallazine therapy. However, it is not as potent as minoxidil.", "contents": "Labetalol in the treatment of hypertensive renal patients. The efficacy of labetalol in lowering blood pressure was assessed in 18 patients with chronic renal failure and hypertension. Before the start of labetalol therapy, all patients were receiving combined antihypertensive therapy, the most common being a beta-blocker and hydrallazine. Over the period of about four weeks labetalol was substituted for the prior therapy. 51Cr edetic acid (EDTA) estimations of glomerular filtration rate were performed before labetalol therapy, and then again after one and six months. Before the therapy with labetalol, 12 of the 18 patients had supine diastolic blood pressures of 100 mm Hg or more. At six months, 14 patients remained in the trial and, of these, only four had a supine diastolic blood pressure of 100 mm Hg or more. In the supine position there was a significant reduction of systolic, but not of diastolic, blood pressure. However, in the erect position there was a significant reduction both in systolic and in diastolic blood presure. Pulse rate did not vary significantly. Few side effects were encountered, transient postural dizziness being the most common side effect. Labetalol seems to be an effective substitute for the beta-blocker plus hydrallazine therapy. However, it is not as potent as minoxidil."}
{"id": "PMID:26012", "title": "[Acidophilic thermotolerant Candida utilis yeast strain obtained by continuous cultivation].", "content": "An acidophilic thermotolerant strain of Candida utilis 1668-3-37 was produced under conditions of continuous cultivation during 128 days. The optimum pH is 3.0-4.5 at 32 degrees C. The strain grows with mumax=0.30 hr(-1) at 37-38 degrees C and the same pH values if dry yeast autolysate (0.05%) is added to the medium.", "contents": "[Acidophilic thermotolerant Candida utilis yeast strain obtained by continuous cultivation]. An acidophilic thermotolerant strain of Candida utilis 1668-3-37 was produced under conditions of continuous cultivation during 128 days. The optimum pH is 3.0-4.5 at 32 degrees C. The strain grows with mumax=0.30 hr(-1) at 37-38 degrees C and the same pH values if dry yeast autolysate (0.05%) is added to the medium."}
{"id": "PMID:26013", "title": "[Metal content in Bacillus megaterium cells under different cultivation conditions].", "content": "The content of K, Na, Mg, Fe, Al, Ba, Sr and Cu was studied in the cells of a chemostal culture of Bacillus megaterium whose growth was limited with citrate, the growth rates being D=mu=0.2, 0.4 and 0.7 hr(-1). The growth was affected also by acid and alkaline values of pH. The content of metals in the cells could change tenfold, depending on their physiological state. The content of Ca, Mg and Fe increased with the growth rate while that of K remained constant. The content of metals changed even more sharply, depending on pH. In the alkaline medium, the content of K, Na, Mg, Ca and Fe decreased, in contrast to that of Al, Ba, Sr and Cu, probably as a result of damaged transport.", "contents": "[Metal content in Bacillus megaterium cells under different cultivation conditions]. The content of K, Na, Mg, Fe, Al, Ba, Sr and Cu was studied in the cells of a chemostal culture of Bacillus megaterium whose growth was limited with citrate, the growth rates being D=mu=0.2, 0.4 and 0.7 hr(-1). The growth was affected also by acid and alkaline values of pH. The content of metals in the cells could change tenfold, depending on their physiological state. The content of Ca, Mg and Fe increased with the growth rate while that of K remained constant. The content of metals changed even more sharply, depending on pH. In the alkaline medium, the content of K, Na, Mg, Ca and Fe decreased, in contrast to that of Al, Ba, Sr and Cu, probably as a result of damaged transport."}
{"id": "PMID:26019", "title": "Specific inactivation of heterospecific transforming DNA by a factor derived from Streptococcus sanguis lysates.", "content": "A heat-sensitive factor obtained from lysates of competent Streptococcus sanguis cells reacts specifically with native DNA of heterospecific (S. pneumoniae or calf thymus) origin. In vitro it does not alter the double or single strand length of the DNA, nor does it affect uptake of the DNA by compentent S. pneumoniae cells in DNase I-resistant form. Following uptake, however, DNA previously exposed to the factor loses over 90% of its biological activity. Reaction of heterospecific DNA with the factor is competitive, suggesting a competition for binding to the factor. Heating treated DNA prior to its reaction with recipient cells, apparently by irreversibly dissociating the factor, restores to the DNA its original potential transforming activity. Specific activity of the factor can be increased in cells grown under certain conditions; this increase is blocked by erythromycin.", "contents": "Specific inactivation of heterospecific transforming DNA by a factor derived from Streptococcus sanguis lysates. A heat-sensitive factor obtained from lysates of competent Streptococcus sanguis cells reacts specifically with native DNA of heterospecific (S. pneumoniae or calf thymus) origin. In vitro it does not alter the double or single strand length of the DNA, nor does it affect uptake of the DNA by compentent S. pneumoniae cells in DNase I-resistant form. Following uptake, however, DNA previously exposed to the factor loses over 90% of its biological activity. Reaction of heterospecific DNA with the factor is competitive, suggesting a competition for binding to the factor. Heating treated DNA prior to its reaction with recipient cells, apparently by irreversibly dissociating the factor, restores to the DNA its original potential transforming activity. Specific activity of the factor can be increased in cells grown under certain conditions; this increase is blocked by erythromycin."}
{"id": "PMID:26020", "title": "The properties of mnemiopsin, a bioluminescent and light sensitive protein purified by hollow fiber techniques.", "content": "A calcium activated photoprotein, termed mnemiopsin, which emits bioluminescence upon the addition of calcium ion, has been isolated from the Ctenophore, Memiopsis leidyi, and purified by hollow fiber techniques. The system is similar to aequorin, from the jellyfish Aequorea, except that mnemiopsin can be light-inactivated. Separation of mnemiopsin from the dilute and large volume animal homogenate proved difficult with conventional biochemical techniques. A continuous flow process utilizing large surface area hollow fibers for filtration, concentration, and dialysis was developed which may also be applicable to the purification of other proteins. The resulting mnemiopsin concentrate, after further purification, was judged to be about 90% pure by its gel electrophoretic profile. Estimates by molecular sieve chromatography and SDS gel electrophoresis gave a molecular weight of about 23,000 daltons. A calcium specificity for triggering light emission was studied by comparison of triggering with a variety of cations and anions and by investigating the effects of calcium ionophores and antagonists. The activity of mnemiospin was characterized with respect to pH, temperature and ionic strength. The stability of mnemiopsin activity after exposure to proteases, denaturants, protein group specific reagents, detergents, elevated temperatures and light was determined. Some years ago our laboratory reported that the bioluminescence reaction in the ctenophores which had long eluded definition involved a calcium activated photoprotein similar in many respects to that found in other coelenterates, notably Aequorea. We found, moreover, that the systems differed in that the bioluminescent activity of the isolated protein was lost following exposure to light. The purification and characterization of this biochemical system was undertaken both in our laboratory and by Ward and Seliger. These latter reports provide a detailed and firm foundation for the understanding of the components and mechanisms involved. While many of our results are in agreement with theirs, our approaches, inquiries, and results differed in several significant ways, the description of which forms the basis for this report. In particular, we took a different approach in the purification of the Mnemiopsis photoprotein which in itself is rather a formidable task. The technique was successful and may point the way to other applications where large volume dilute solutions prove cumbersome. Secondly, our study of the effects of salts, proteases, detergents, and other agents indicate that the protein, though sensitive to calcium and visible light inactivation, is relatively resistant to some agents which commonly inactivate proteins.", "contents": "The properties of mnemiopsin, a bioluminescent and light sensitive protein purified by hollow fiber techniques. A calcium activated photoprotein, termed mnemiopsin, which emits bioluminescence upon the addition of calcium ion, has been isolated from the Ctenophore, Memiopsis leidyi, and purified by hollow fiber techniques. The system is similar to aequorin, from the jellyfish Aequorea, except that mnemiopsin can be light-inactivated. Separation of mnemiopsin from the dilute and large volume animal homogenate proved difficult with conventional biochemical techniques. A continuous flow process utilizing large surface area hollow fibers for filtration, concentration, and dialysis was developed which may also be applicable to the purification of other proteins. The resulting mnemiopsin concentrate, after further purification, was judged to be about 90% pure by its gel electrophoretic profile. Estimates by molecular sieve chromatography and SDS gel electrophoresis gave a molecular weight of about 23,000 daltons. A calcium specificity for triggering light emission was studied by comparison of triggering with a variety of cations and anions and by investigating the effects of calcium ionophores and antagonists. The activity of mnemiospin was characterized with respect to pH, temperature and ionic strength. The stability of mnemiopsin activity after exposure to proteases, denaturants, protein group specific reagents, detergents, elevated temperatures and light was determined. Some years ago our laboratory reported that the bioluminescence reaction in the ctenophores which had long eluded definition involved a calcium activated photoprotein similar in many respects to that found in other coelenterates, notably Aequorea. We found, moreover, that the systems differed in that the bioluminescent activity of the isolated protein was lost following exposure to light. The purification and characterization of this biochemical system was undertaken both in our laboratory and by Ward and Seliger. These latter reports provide a detailed and firm foundation for the understanding of the components and mechanisms involved. While many of our results are in agreement with theirs, our approaches, inquiries, and results differed in several significant ways, the description of which forms the basis for this report. In particular, we took a different approach in the purification of the Mnemiopsis photoprotein which in itself is rather a formidable task. The technique was successful and may point the way to other applications where large volume dilute solutions prove cumbersome. Secondly, our study of the effects of salts, proteases, detergents, and other agents indicate that the protein, though sensitive to calcium and visible light inactivation, is relatively resistant to some agents which commonly inactivate proteins."}
{"id": "PMID:26021", "title": "Extraction of tyrosine aminotransferase mRNA by polyribosome immunosorption on sepharose 4B.", "content": "Sepharose 4B column with antibody to tyrosine aminotransferase (E.C. 2.6.1.5) (TAT) covalently bound can selectively remove a specific fraction of TAT polysomes from rat liver homogenates. From the polysomes which was adsorbed by immunosorbent one may obtain mRNA containing a segment of poly-adenilate-rich residues, having sedimentation constant of 11--16S. This mRNA may program synthesis of the specific protein in a cell free system. Near 70% of the protein was synthesized in such a system, may react with the antibody to TAT.", "contents": "Extraction of tyrosine aminotransferase mRNA by polyribosome immunosorption on sepharose 4B. Sepharose 4B column with antibody to tyrosine aminotransferase (E.C. 2.6.1.5) (TAT) covalently bound can selectively remove a specific fraction of TAT polysomes from rat liver homogenates. From the polysomes which was adsorbed by immunosorbent one may obtain mRNA containing a segment of poly-adenilate-rich residues, having sedimentation constant of 11--16S. This mRNA may program synthesis of the specific protein in a cell free system. Near 70% of the protein was synthesized in such a system, may react with the antibody to TAT."}
{"id": "PMID:26028", "title": "The binding of intravenous and oral biliary contrast agents to human and bovine serum albumin.", "content": "The binding of two homologous series of oral and intravenous biliary contrast agents to human and bovine serum albumin was investigated using the gel filtration technique. All intravenous compounds are bound to human serum albumin via one high affinity and several low affinity binding sites. Within the concentration range investigated, about 3--5 high affinity binding sites for the oral compounds were found on human serum albumin. In general, the intravenous compounds have a greater affinity for human serum albumin than the oral compounds. No significant differences were found for the binding of the oral compounds to human or bovine serum albumin, while the intravenous compounds have a higher affinity for bovine than for human serum albumin. The significance of the plasma protein binding of the biliary contrast agents for the hepatic uptake is discussed.", "contents": "The binding of intravenous and oral biliary contrast agents to human and bovine serum albumin. The binding of two homologous series of oral and intravenous biliary contrast agents to human and bovine serum albumin was investigated using the gel filtration technique. All intravenous compounds are bound to human serum albumin via one high affinity and several low affinity binding sites. Within the concentration range investigated, about 3--5 high affinity binding sites for the oral compounds were found on human serum albumin. In general, the intravenous compounds have a greater affinity for human serum albumin than the oral compounds. No significant differences were found for the binding of the oral compounds to human or bovine serum albumin, while the intravenous compounds have a higher affinity for bovine than for human serum albumin. The significance of the plasma protein binding of the biliary contrast agents for the hepatic uptake is discussed."}
{"id": "PMID:26036", "title": "[Hemorrhagic rectocolitis. Attempt at programmed therapy].", "content": "Planned treatment of 30 cases of haemorrhagic colitis is reported. Its protocol included salazopyrine and benzodiazepine per os, salazopyrine and prednisone per rectum, and parenteral ACTH depot. Administration for 60 days brought good results in cases of slight or average severity. Recurrences, albeit less severe, were not prevented, however. Attention is drawn to the need to follow up this  group of patients for a longer period. Even so, it is felt that the effect of this form of treatment is primarily symptomatic.", "contents": "[Hemorrhagic rectocolitis. Attempt at programmed therapy]. Planned treatment of 30 cases of haemorrhagic colitis is reported. Its protocol included salazopyrine and benzodiazepine per os, salazopyrine and prednisone per rectum, and parenteral ACTH depot. Administration for 60 days brought good results in cases of slight or average severity. Recurrences, albeit less severe, were not prevented, however. Attention is drawn to the need to follow up this  group of patients for a longer period. Even so, it is felt that the effect of this form of treatment is primarily symptomatic."}
{"id": "PMID:26038", "title": "Expression of hormonally induced tyrosine aminotransferase in host liver and Morris hepatoma No. 7777 during cofactor depletion.", "content": "Cytoplasmic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC2.6.1.5) was partially purified from host liver and Morris hepatoma No. 7777 grown in pyridoxine depleted rats. The animals were sacrificed six hours following the intraperitoneal administration of hydrocortisone hemisuccinate. Enzyme preparations were subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Six and at least three enzymatically active protein peaks were detected in host liver and the hepatoma, respectively, by this method.", "contents": "Expression of hormonally induced tyrosine aminotransferase in host liver and Morris hepatoma No. 7777 during cofactor depletion. Cytoplasmic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase, EC2.6.1.5) was partially purified from host liver and Morris hepatoma No. 7777 grown in pyridoxine depleted rats. The animals were sacrificed six hours following the intraperitoneal administration of hydrocortisone hemisuccinate. Enzyme preparations were subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Six and at least three enzymatically active protein peaks were detected in host liver and the hepatoma, respectively, by this method."}
{"id": "PMID:26041", "title": "[The detection of bacterial antigens by counter-immunoelectrophoresis in N. meningitidis, H. influenzae serotype b, S. pneumoniae infections. Diagnostic value and evolutive aspect (in 216 cases) (author's transl)].", "content": "Using counterimmunoelectrophoresis (CIE) the authors have assayed for soluble bacterial S. pneumoniae, N meningitidis group A, B, C. H. influenzae type b antigens, biological fluids in 216 patients (meningitis: 136; pneumonia: 76; miscellaneous: 4) during 16 months. Because of heterogeneous recruiting (the bacteriology was carried out by different laboratories) the increase in aetiological diagnosis given by CIE is only statistically valid for the bacteriologic negative group when blind antibiotic therapy had already been given. In this group, CIE makes a notable increase in diagnosis of 22,1 % +/- 10,1 in meningitis and 25,5% +/- 12,7 in pneumonia. Various physiopathological aspects are considered concerning soluble bacterial antigens detection during the course of the disease. This method seems very useful and accurate; and therefore should be used in every microbiologic laboratory.", "contents": "[The detection of bacterial antigens by counter-immunoelectrophoresis in N. meningitidis, H. influenzae serotype b, S. pneumoniae infections. Diagnostic value and evolutive aspect (in 216 cases) (author's transl)]. Using counterimmunoelectrophoresis (CIE) the authors have assayed for soluble bacterial S. pneumoniae, N meningitidis group A, B, C. H. influenzae type b antigens, biological fluids in 216 patients (meningitis: 136; pneumonia: 76; miscellaneous: 4) during 16 months. Because of heterogeneous recruiting (the bacteriology was carried out by different laboratories) the increase in aetiological diagnosis given by CIE is only statistically valid for the bacteriologic negative group when blind antibiotic therapy had already been given. In this group, CIE makes a notable increase in diagnosis of 22,1 % +/- 10,1 in meningitis and 25,5% +/- 12,7 in pneumonia. Various physiopathological aspects are considered concerning soluble bacterial antigens detection during the course of the disease. This method seems very useful and accurate; and therefore should be used in every microbiologic laboratory."}
{"id": "PMID:26042", "title": "A new method for the purification and identification of covalently closed circular DNA molcules.", "content": "A new technique has been developed for the rapid isolation of covalently closed circular DNA molecules. The procedure is a selective extraction based on differences in the partitioning of covalently closed circular DNA molecules and noncovalently closed species between phenol and water at acid pH and low ionic strength. Under the conditions described, linear as well as nicked circular DNA is extracted into phenol, while covalently closed circular DNA molecules remain in the water phase. The method permits the quantitative isolation of covalently closed circular DNA from either total cellular DNA or partially purified preparations, to a degree of purity comparable with buoyant density procedures.", "contents": "A new method for the purification and identification of covalently closed circular DNA molcules. A new technique has been developed for the rapid isolation of covalently closed circular DNA molecules. The procedure is a selective extraction based on differences in the partitioning of covalently closed circular DNA molecules and noncovalently closed species between phenol and water at acid pH and low ionic strength. Under the conditions described, linear as well as nicked circular DNA is extracted into phenol, while covalently closed circular DNA molecules remain in the water phase. The method permits the quantitative isolation of covalently closed circular DNA from either total cellular DNA or partially purified preparations, to a degree of purity comparable with buoyant density procedures."}
{"id": "PMID:26043", "title": "Synthesis and properties of 8-azido-1, N6-etheno adenosine triphosphate--a fluorescent and photosensitive ATP analog.", "content": "8-Azido-1,N6-etheno-ATP--a fluorescent and photoreactive ATP analog has been synthesized and characterized by elementary analysis, thin layer chromatography, infrared spectroscopy, proton resonance spectroscopy, UV absorption spectroscopy, and fluorescence spectroscopy. The photolytical decomposition upon irradiation at different pH values is tested.", "contents": "Synthesis and properties of 8-azido-1, N6-etheno adenosine triphosphate--a fluorescent and photosensitive ATP analog. 8-Azido-1,N6-etheno-ATP--a fluorescent and photoreactive ATP analog has been synthesized and characterized by elementary analysis, thin layer chromatography, infrared spectroscopy, proton resonance spectroscopy, UV absorption spectroscopy, and fluorescence spectroscopy. The photolytical decomposition upon irradiation at different pH values is tested."}
{"id": "PMID:26044", "title": "Short RNA chains synthesized at low pH are initiated at promoter sites.", "content": "Under non optimal conditions- either with limiting substrate concentrations (1) or at low pH (2)- RNA polymerase of Escherichia coli synthesizes very short RNA chains. By sequencing one RNA species synthesized at pH 5.8 upon T7 DNA we were able to demonstrate that under these conditions transcription is initiated at a normal promoter site (here A1) but however is terminated soon afterwards at specific artificial sites not used in vivo.", "contents": "Short RNA chains synthesized at low pH are initiated at promoter sites. Under non optimal conditions- either with limiting substrate concentrations (1) or at low pH (2)- RNA polymerase of Escherichia coli synthesizes very short RNA chains. By sequencing one RNA species synthesized at pH 5.8 upon T7 DNA we were able to demonstrate that under these conditions transcription is initiated at a normal promoter site (here A1) but however is terminated soon afterwards at specific artificial sites not used in vivo."}
{"id": "PMID:26050", "title": "[Polarographic method of determining phenol in the air].", "content": "A specific, highly sensitive and exact polarographic method of phenol determination in the air is developed. The conditions of sample taking are outlined, and the effect of polarographic solution pH on the height of step and semi-wave potential is verified. The suggested method is readily applicable simple for execution, and provides for a good reproducibility and promptness of determination during productional tests.", "contents": "[Polarographic method of determining phenol in the air]. A specific, highly sensitive and exact polarographic method of phenol determination in the air is developed. The conditions of sample taking are outlined, and the effect of polarographic solution pH on the height of step and semi-wave potential is verified. The suggested method is readily applicable simple for execution, and provides for a good reproducibility and promptness of determination during productional tests."}
{"id": "PMID:26051", "title": "Minichromosome from BK virus as a template for transcription in vitro.", "content": "BK virus DNA can be extracted from virions as a nucleoprotein complex containing about 20 nucleosomes. Transcription of this \"minichromosome\" with Escherichia coli RNA polymerase indicates that both initiation and elongation of RNA chains are reduced by the presence of nucleosomes. Hybridization analysis of RNA made on the complex shows preferential transcription of one region of BK virus genome. No increase in strand selection is observed with respect to transcription of purified superhelical BK virus DNA.", "contents": "Minichromosome from BK virus as a template for transcription in vitro. BK virus DNA can be extracted from virions as a nucleoprotein complex containing about 20 nucleosomes. Transcription of this \"minichromosome\" with Escherichia coli RNA polymerase indicates that both initiation and elongation of RNA chains are reduced by the presence of nucleosomes. Hybridization analysis of RNA made on the complex shows preferential transcription of one region of BK virus genome. No increase in strand selection is observed with respect to transcription of purified superhelical BK virus DNA."}
{"id": "PMID:26052", "title": "Transglutaminase activity in human lymphocytes: early activation by phytomitogens.", "content": "Transglutaminase activity is present in human peripheral lymphocytes and is enhanced up to 15-fold within 10-30 min after treatment of the cells with concanavalin A. Phytohemagglutinin has a similar effect. The enzyme is not detected when intact cells are assayed; it is detected only in cell lysates. Concanavalin A enhances transglutaminase activity only when it is incubated with intact cells; concanavalin A treatment of cell lysates has no effect, alpha-Methyl-D-mannoside specifically inhibits the enhancement of transglutaminase activity in cells treated with concanavalin A results from the specific interaction of the lectin with its saccharide binding site on the cell surface, rather than by direct interaction with the enzyme itself. The increased activity of transglutaminase in cells treated with concanavalin A, as compared to unstimulated cells, is maintained under assay conditions in which saturating levels of Ca2+ are present. Transglutaminase may be involved in early cellular events leading to lymphocyte blastogenesis.", "contents": "Transglutaminase activity in human lymphocytes: early activation by phytomitogens. Transglutaminase activity is present in human peripheral lymphocytes and is enhanced up to 15-fold within 10-30 min after treatment of the cells with concanavalin A. Phytohemagglutinin has a similar effect. The enzyme is not detected when intact cells are assayed; it is detected only in cell lysates. Concanavalin A enhances transglutaminase activity only when it is incubated with intact cells; concanavalin A treatment of cell lysates has no effect, alpha-Methyl-D-mannoside specifically inhibits the enhancement of transglutaminase activity in cells treated with concanavalin A results from the specific interaction of the lectin with its saccharide binding site on the cell surface, rather than by direct interaction with the enzyme itself. The increased activity of transglutaminase in cells treated with concanavalin A, as compared to unstimulated cells, is maintained under assay conditions in which saturating levels of Ca2+ are present. Transglutaminase may be involved in early cellular events leading to lymphocyte blastogenesis."}
{"id": "PMID:26053", "title": "Topographical analysis of regulatory and metal ion binding sites on glutamine synthetase from Escherichia coli: 13C and 31P nuclear magnetic resonance and fluorescence energy transfer study.", "content": "The paramagnetic effect of Mn(II) on (13)C and (31)P nuclear magnetic resonance signals from the [2-(13)C]ATP adenylylated glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming); EC 6.3.1.2] from Escherichia coli was measured. This effect permitted the determination of distances from the 2-C position and the phosphorus of covalently bound AMP to the two Mn(II) binding sites, n(1) and n(2). Binding of Mn(II) to the n(1) site converts an inactive apo-enzyme to its active form, while the metal ion bound at n(2) occupies the metal-nucleotide substrate site. The distances from Mn(II) at the n(1) and n(2) sites to phosphorus are approximately 10 and approximately 7 A and to the 2-C position of the adenine ring are approximately 12 and approximately 11 A, respectively. The fluorescence energy transfer method was used to determine distances between Co(II) at n(1) and n(2) and the adenylyl site. For this experiment the enzyme was adenylylated with epsilon-ATP. The distances between epsilon-adenine and Co(II) at n(1) and n(2) are approximately 13 and approximately 11 A, respectively. Quantitation of the paramagnetic effect due to Co(II) on the (31)P nuclear magnetic resonance signal yielded values of 8 and 6 A for the distances between the phosphorus of the covalently bound AMP and the n(1) and n(2) sites, respectively. The results reveal that the covalent modification site is very close to the catalytic center of the enzyme. In this study both nuclear magnetic resonance and fluorescence energy transfer techniques have been used to determine distances between the same set of sites on an enzyme surface.", "contents": "Topographical analysis of regulatory and metal ion binding sites on glutamine synthetase from Escherichia coli: 13C and 31P nuclear magnetic resonance and fluorescence energy transfer study. The paramagnetic effect of Mn(II) on (13)C and (31)P nuclear magnetic resonance signals from the [2-(13)C]ATP adenylylated glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming); EC 6.3.1.2] from Escherichia coli was measured. This effect permitted the determination of distances from the 2-C position and the phosphorus of covalently bound AMP to the two Mn(II) binding sites, n(1) and n(2). Binding of Mn(II) to the n(1) site converts an inactive apo-enzyme to its active form, while the metal ion bound at n(2) occupies the metal-nucleotide substrate site. The distances from Mn(II) at the n(1) and n(2) sites to phosphorus are approximately 10 and approximately 7 A and to the 2-C position of the adenine ring are approximately 12 and approximately 11 A, respectively. The fluorescence energy transfer method was used to determine distances between Co(II) at n(1) and n(2) and the adenylyl site. For this experiment the enzyme was adenylylated with epsilon-ATP. The distances between epsilon-adenine and Co(II) at n(1) and n(2) are approximately 13 and approximately 11 A, respectively. Quantitation of the paramagnetic effect due to Co(II) on the (31)P nuclear magnetic resonance signal yielded values of 8 and 6 A for the distances between the phosphorus of the covalently bound AMP and the n(1) and n(2) sites, respectively. The results reveal that the covalent modification site is very close to the catalytic center of the enzyme. In this study both nuclear magnetic resonance and fluorescence energy transfer techniques have been used to determine distances between the same set of sites on an enzyme surface."}
{"id": "PMID:26054", "title": "Composition of vacuoles and sarcoplasmic reticulum in fatigued muscle: electron probe analysis.", "content": "Electron probe analysis, cryo-ultramicrotomy, and freeze-substitution were used to determine the nature of vacuolation and the subcellular composition in fatigued frog skeletal muscle fibers. The vacuoles caused by fatigue were part of the T-tubule system and contained high concentrations of NaCl. The calcium concentration in the terminal cisternae was higher than previously measured normal resting values. Mitochondrial calcium content was relatively low (mean +/- SEM, 2 +/- 2 mmol/kg dry weight). Fiber NaCl was increased. It is concluded that fatigue is not due to the depletion of calcium stores from the terminal cisternae or to uncoupling of mitochondria due to calcium loading but may be caused by multiple mechanisms including failure of the T-tubule action potential.", "contents": "Composition of vacuoles and sarcoplasmic reticulum in fatigued muscle: electron probe analysis. Electron probe analysis, cryo-ultramicrotomy, and freeze-substitution were used to determine the nature of vacuolation and the subcellular composition in fatigued frog skeletal muscle fibers. The vacuoles caused by fatigue were part of the T-tubule system and contained high concentrations of NaCl. The calcium concentration in the terminal cisternae was higher than previously measured normal resting values. Mitochondrial calcium content was relatively low (mean +/- SEM, 2 +/- 2 mmol/kg dry weight). Fiber NaCl was increased. It is concluded that fatigue is not due to the depletion of calcium stores from the terminal cisternae or to uncoupling of mitochondria due to calcium loading but may be caused by multiple mechanisms including failure of the T-tubule action potential."}
{"id": "PMID:26055", "title": "Regulation of glutamine synthetase in cultured 3T3-L1 cells by insulin, hydrocortisone, and dibutyryl cyclic AMP.", "content": "The 3T3-L1 mouse fibroblast cell line develops morphological and biochemical characteristics of adipocytes when maintained at confluence. This conversion to adipocytes is accelerated by addition of insulin to the culture medium [Green, H. & Kehinde, O. (1975) Cell 5, 19-27]. During the course of the insulin-mediated adipocyte conversion, the specific activity (units/mg of protein) of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] increases more than 100-fold. The specific activities of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) and glucose-6-P dehydrogenase (D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49) also increase but less dramatically (1.5- to 3-fold). In contrast, confluent cells maintained in the absence of insulin for the same time (12-20 days after confluence) display only minimal increases in the activity of these enzymes. Maintenance of confluent cells in culture medium lacking added L-glutamine has little, if any, effect on glutamine synthetase activity in either control or insulin-treated cultures. Treatment of confluent 3T3-L1 cultures with hydrocortisone (1 mug/ml) for 3 days prior to harvesting results in an increase in glutamine synthetase specific activity of 12-fold for control cultures maintained for 13 days in the absence of insulin and 1.4-fold for adipocyte cultures maintained for 13 days in the presence of insulin (10 mug/ml). Treatment of 3T3-L1 control cells and adipocytes with dibutyryl cyclic AMP (1 mM) plus theophylline (1 mM) decreases the glutamine synthetase specific activity and almost completely reverses the insulin- and hydrocortisone-mediated increases in enzyme activity. In contrast, treatment with dibutyryl cyclic AMP plus theophylline has relatively little effect on the specific activities of hexokinase or glucose-6-P dehydrogenase or on the protein content of the cultures. These data indicate that glutamine synthetase activity is hormonally regulated in 3T3-L1 cells.", "contents": "Regulation of glutamine synthetase in cultured 3T3-L1 cells by insulin, hydrocortisone, and dibutyryl cyclic AMP. The 3T3-L1 mouse fibroblast cell line develops morphological and biochemical characteristics of adipocytes when maintained at confluence. This conversion to adipocytes is accelerated by addition of insulin to the culture medium [Green, H. & Kehinde, O. (1975) Cell 5, 19-27]. During the course of the insulin-mediated adipocyte conversion, the specific activity (units/mg of protein) of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] increases more than 100-fold. The specific activities of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) and glucose-6-P dehydrogenase (D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49) also increase but less dramatically (1.5- to 3-fold). In contrast, confluent cells maintained in the absence of insulin for the same time (12-20 days after confluence) display only minimal increases in the activity of these enzymes. Maintenance of confluent cells in culture medium lacking added L-glutamine has little, if any, effect on glutamine synthetase activity in either control or insulin-treated cultures. Treatment of confluent 3T3-L1 cultures with hydrocortisone (1 mug/ml) for 3 days prior to harvesting results in an increase in glutamine synthetase specific activity of 12-fold for control cultures maintained for 13 days in the absence of insulin and 1.4-fold for adipocyte cultures maintained for 13 days in the presence of insulin (10 mug/ml). Treatment of 3T3-L1 control cells and adipocytes with dibutyryl cyclic AMP (1 mM) plus theophylline (1 mM) decreases the glutamine synthetase specific activity and almost completely reverses the insulin- and hydrocortisone-mediated increases in enzyme activity. In contrast, treatment with dibutyryl cyclic AMP plus theophylline has relatively little effect on the specific activities of hexokinase or glucose-6-P dehydrogenase or on the protein content of the cultures. These data indicate that glutamine synthetase activity is hormonally regulated in 3T3-L1 cells."}
{"id": "PMID:26062", "title": "Crosslinking of the nearest membrane protein neighbors in ATP depleted, calcium enriched and irreversibly sickled red cells.", "content": "ATP depleted or Ca2+ (0.1 mM) enriched normal red cells (greater than 80% echinocytes III) subjected to crosslinking by catalytic oxidation contain a greater than 1,000,000 daltons spectrin rich polymer cleavable by dithiothreitol (DTT) reduction. Similar complex is seen after glutaraldehyde crosslinking suggesting spectrin rearrangement into closer contacts or aggregation. In addition, a non-reducible greater than 1,000,000 daltons polymer is produced in fresh rbc or ghosts by high (greater than 0.5 mM) Ca2+ conc. and ionophore A23187. This complex is attributed to endogenous membrane protein crosslinking, catalyzed by a Ca2+ stimulated rbc transglutamidase. ISCs exhibiting a 4 fold increase in Ca2+ and a decrease in ATP do not exhibit these polymers. However, ISCs have an increased propensity to form the spectrin rich polymer during a subsequent ATP depletion and this is associated with a transformation of greater than 60% ISCs into spheroechinocytes. Similar cells are occasionally noted (greater than 4%) in the densest ISC rich fractions separated from fresh blood. We conclude that neither Ca2+, ATP dependent spectrin aggregation nor a spontaneous irreversible crosslinking underlie the membrane lesion of ISCs. Accelerated calcium gain and ATP depletion in ISCs leads to spectrin rearrangement and transformation of ISCs into spheroechinocytes which may represent an end stage ISC lesion resulting in an ISC removal from circulation.", "contents": "Crosslinking of the nearest membrane protein neighbors in ATP depleted, calcium enriched and irreversibly sickled red cells. ATP depleted or Ca2+ (0.1 mM) enriched normal red cells (greater than 80% echinocytes III) subjected to crosslinking by catalytic oxidation contain a greater than 1,000,000 daltons spectrin rich polymer cleavable by dithiothreitol (DTT) reduction. Similar complex is seen after glutaraldehyde crosslinking suggesting spectrin rearrangement into closer contacts or aggregation. In addition, a non-reducible greater than 1,000,000 daltons polymer is produced in fresh rbc or ghosts by high (greater than 0.5 mM) Ca2+ conc. and ionophore A23187. This complex is attributed to endogenous membrane protein crosslinking, catalyzed by a Ca2+ stimulated rbc transglutamidase. ISCs exhibiting a 4 fold increase in Ca2+ and a decrease in ATP do not exhibit these polymers. However, ISCs have an increased propensity to form the spectrin rich polymer during a subsequent ATP depletion and this is associated with a transformation of greater than 60% ISCs into spheroechinocytes. Similar cells are occasionally noted (greater than 4%) in the densest ISC rich fractions separated from fresh blood. We conclude that neither Ca2+, ATP dependent spectrin aggregation nor a spontaneous irreversible crosslinking underlie the membrane lesion of ISCs. Accelerated calcium gain and ATP depletion in ISCs leads to spectrin rearrangement and transformation of ISCs into spheroechinocytes which may represent an end stage ISC lesion resulting in an ISC removal from circulation."}
{"id": "PMID:26063", "title": "Pipradrol enhances reinforcing properties of stimuli paired with brain stimulation.", "content": "The hypothesis that a psychomotor stimulant drug (pipradrol) enhances the reinforcing effects of stimuli paired with reinforcing brain stimulation was tested using a conditioned reinforcement paradigm. Rats were trained to discriminate between two stimuli (S+ and S-) to obtain ICS in the lateral hypothalamus by pushing a panel in the presence of S+. In a subsequent preference test, ICS was no longer available, but responding on one of two novel levers now produced S+, whereas responding on the other lever produced S-. Four groups of four rats received 0, 5, 10 or 15 mg/kg pipradrol. Doses of 5 and 10 mg/kg significantly enhanced the preference for S+ over S-. These doses increased responding for S+, but had no effect on responding for S-. These results support the hypothesis tested, and suggest that pipradrol potentiates the effects of conditioned reinforcement.", "contents": "Pipradrol enhances reinforcing properties of stimuli paired with brain stimulation. The hypothesis that a psychomotor stimulant drug (pipradrol) enhances the reinforcing effects of stimuli paired with reinforcing brain stimulation was tested using a conditioned reinforcement paradigm. Rats were trained to discriminate between two stimuli (S+ and S-) to obtain ICS in the lateral hypothalamus by pushing a panel in the presence of S+. In a subsequent preference test, ICS was no longer available, but responding on one of two novel levers now produced S+, whereas responding on the other lever produced S-. Four groups of four rats received 0, 5, 10 or 15 mg/kg pipradrol. Doses of 5 and 10 mg/kg significantly enhanced the preference for S+ over S-. These doses increased responding for S+, but had no effect on responding for S-. These results support the hypothesis tested, and suggest that pipradrol potentiates the effects of conditioned reinforcement."}
{"id": "PMID:26066", "title": "Nucleosome structure.", "content": "Electron microscopic and biochemical results are presented supporting the following conclusions: (1) Two molecules of each histone H2A, H2B, H3 and H4 are necessary and sufficient to form a nucleosome with a diameter of 12.5 +/- 1 nm and containing about 200 base pairs of DNA. (2) H3 plus H4 alone can compact 129 +/- 8 DNA base pairs into a sub-nucleosomal particle with a diameter of 8 +/- 1 nm. In such a particle the DNA duplex is under a constraint equivalent to negative superhelicity. (3) Chromatin should be viewed as a dynamic structure, oscillating between a compact structure (the nucleosome) and more open structures, depending on the environmental conditions.", "contents": "Nucleosome structure. Electron microscopic and biochemical results are presented supporting the following conclusions: (1) Two molecules of each histone H2A, H2B, H3 and H4 are necessary and sufficient to form a nucleosome with a diameter of 12.5 +/- 1 nm and containing about 200 base pairs of DNA. (2) H3 plus H4 alone can compact 129 +/- 8 DNA base pairs into a sub-nucleosomal particle with a diameter of 8 +/- 1 nm. In such a particle the DNA duplex is under a constraint equivalent to negative superhelicity. (3) Chromatin should be viewed as a dynamic structure, oscillating between a compact structure (the nucleosome) and more open structures, depending on the environmental conditions."}
{"id": "PMID:26068", "title": "Relation of nucleosomes to nucleotide sequences in the rat.", "content": "The relation of nucleosomes to nucleotide sequences is random for most single copy sequences in rat liver. This could be due to variation in the DNA content of nucleosomes, and a procedure for detecting such variation is described.", "contents": "Relation of nucleosomes to nucleotide sequences in the rat. The relation of nucleosomes to nucleotide sequences is random for most single copy sequences in rat liver. This could be due to variation in the DNA content of nucleosomes, and a procedure for detecting such variation is described."}
{"id": "PMID:26072", "title": "Conformational flexibility in DNA structure and its implications in understanding the organization of DNA in chromatin.", "content": "X-ray crystallographic studies of drug-nucleic acid crystalline complexes have suggested that DNA first bends or 'kinks' before accepting an intercalative drug or dye. This flexibility in DNA structure is made possible by altering the normal C2' endo deoxyribose sugar puckering in B DNA to a mixed sugar puckering pattern of the type C3' endo (3'-5') C2' endo and partially unstacking base pairs. A kinking scheme such as this would require minimal sterochemical rearrangement and would also involve small energies. This has prompted us to ask more generally if a conformational change such as this could be used by proteins in their interactions with DNA. Here we describe an interesting superhelical DNA structure formed by kinking DNA every ten base pairs. This structure may be used in the organization of DNA within the nucleosome structure in chromatin.", "contents": "Conformational flexibility in DNA structure and its implications in understanding the organization of DNA in chromatin. X-ray crystallographic studies of drug-nucleic acid crystalline complexes have suggested that DNA first bends or 'kinks' before accepting an intercalative drug or dye. This flexibility in DNA structure is made possible by altering the normal C2' endo deoxyribose sugar puckering in B DNA to a mixed sugar puckering pattern of the type C3' endo (3'-5') C2' endo and partially unstacking base pairs. A kinking scheme such as this would require minimal sterochemical rearrangement and would also involve small energies. This has prompted us to ask more generally if a conformational change such as this could be used by proteins in their interactions with DNA. Here we describe an interesting superhelical DNA structure formed by kinking DNA every ten base pairs. This structure may be used in the organization of DNA within the nucleosome structure in chromatin."}
{"id": "PMID:26073", "title": "The structure of SV 40 chromatin.", "content": "Simian virus 40 (SV40) nucleoprotein complexes were studied with the electron microscope. Depending on the isolation procedure, SV40 chromatin has two different conformations: complexes isolated in the presence of 0.15 M NaCl appeared as very compact globular structures, while those isolated in the presence of 0.6 M NaCl had the typical 'beads-on-a-string' appearance of the primary nucleofilament. Concomitant with this structural change was a variation in the histone pattern and sedimentation behaviour of the complexes: with NaCl at 0.15 mol 1(-1) the isolated complexes contained both the nucleosomal histones and histone H1, and sedimented in sucrose gradients at 70S. Increasing the ionic strength to 0.6 M NaCl resulted in the removal of histone H1 from the complexes and in a decrease of the sedimentation coefficient to 40S. DNA relaxing enzyme is associated with the SV40 nucleoprotein complexes. The numbers of superhelical turns in DNA from compact and open types of complexes were found to be the same. Therefore the transition from the condensed to the open structure of viral chromatin does not require a change in the topological winding number of its DNA.", "contents": "The structure of SV 40 chromatin. Simian virus 40 (SV40) nucleoprotein complexes were studied with the electron microscope. Depending on the isolation procedure, SV40 chromatin has two different conformations: complexes isolated in the presence of 0.15 M NaCl appeared as very compact globular structures, while those isolated in the presence of 0.6 M NaCl had the typical 'beads-on-a-string' appearance of the primary nucleofilament. Concomitant with this structural change was a variation in the histone pattern and sedimentation behaviour of the complexes: with NaCl at 0.15 mol 1(-1) the isolated complexes contained both the nucleosomal histones and histone H1, and sedimented in sucrose gradients at 70S. Increasing the ionic strength to 0.6 M NaCl resulted in the removal of histone H1 from the complexes and in a decrease of the sedimentation coefficient to 40S. DNA relaxing enzyme is associated with the SV40 nucleoprotein complexes. The numbers of superhelical turns in DNA from compact and open types of complexes were found to be the same. Therefore the transition from the condensed to the open structure of viral chromatin does not require a change in the topological winding number of its DNA."}
{"id": "PMID:26076", "title": "Aspects of the regulation of histone genes.", "content": "Sequencing of cloned histone DNA of the sea urchin Psammechinus miliaris has confirmed the map of the histone genes obtained earlier by rather less refined techniques. Sequencing of spacer has revealed that it is unlikely to code for protein. Some interesting sequences in the prelude regions to the structural genes have been found. The technique of injecting DNA into the germinal vesicle of the Xenopus oocyte has been greatly simplified, so that now many of the parameters governing the transcription of the injected genes can be investigated. Some mRNA-like molecules appear when circular histone DNA is inserted into the oocyte nucleus. We are cautiously optimistic that the technique can be further developed and will provide a useful tool for the study of the molecular mechanisms governing the expression of structural genes coding for proteins.", "contents": "Aspects of the regulation of histone genes. Sequencing of cloned histone DNA of the sea urchin Psammechinus miliaris has confirmed the map of the histone genes obtained earlier by rather less refined techniques. Sequencing of spacer has revealed that it is unlikely to code for protein. Some interesting sequences in the prelude regions to the structural genes have been found. The technique of injecting DNA into the germinal vesicle of the Xenopus oocyte has been greatly simplified, so that now many of the parameters governing the transcription of the injected genes can be investigated. Some mRNA-like molecules appear when circular histone DNA is inserted into the oocyte nucleus. We are cautiously optimistic that the technique can be further developed and will provide a useful tool for the study of the molecular mechanisms governing the expression of structural genes coding for proteins."}
{"id": "PMID:26080", "title": "Organization of transcribed regions of chromatin.", "content": "The endonuclease DNase II preferentially attacks a limited and tissue-specific portion of chromosomal DNA. This material may be separated from the bulk of chromatin DNA by virtue of its solubility in 2 mM MgCl2. The Mg2+ soluble fraction forms a specific subset of DNA sequences and is enriched four to sevenfold in sequences coding for cytoplasmic poly(A)-containing RNA and globin messenger RNA (in globin-producing cells). The bulk (70--90%) of rapidly labelled RNA is found associated with the Mg2+-soluble fraction. Transcriptionally active, Mc2+-soluble chromatin is organized into repeating subunits of DNA (200 +/- 5 base pairs) and histone. Mc2+-soluble active subunits differ from the subunits or nucleosomes of non-transcribed regions in many respects: namely, chemical composition (non-histone protein and RNA), sedimentation properties, differential sensitivity to DNase I and the single-strand-specific nuclease S1, and optical melting behaviour. These results suggest that chromatin subunits adopt a new configuration during the process of transcription.", "contents": "Organization of transcribed regions of chromatin. The endonuclease DNase II preferentially attacks a limited and tissue-specific portion of chromosomal DNA. This material may be separated from the bulk of chromatin DNA by virtue of its solubility in 2 mM MgCl2. The Mg2+ soluble fraction forms a specific subset of DNA sequences and is enriched four to sevenfold in sequences coding for cytoplasmic poly(A)-containing RNA and globin messenger RNA (in globin-producing cells). The bulk (70--90%) of rapidly labelled RNA is found associated with the Mg2+-soluble fraction. Transcriptionally active, Mc2+-soluble chromatin is organized into repeating subunits of DNA (200 +/- 5 base pairs) and histone. Mc2+-soluble active subunits differ from the subunits or nucleosomes of non-transcribed regions in many respects: namely, chemical composition (non-histone protein and RNA), sedimentation properties, differential sensitivity to DNase I and the single-strand-specific nuclease S1, and optical melting behaviour. These results suggest that chromatin subunits adopt a new configuration during the process of transcription."}
{"id": "PMID:26081", "title": "The organization of transcription on lampbrush chromosomes.", "content": "The meiotic lampbrush chromosomes of amphibian oocytes display readily distinguishable regions of transcription (lateral loops) which extend from axial condensates of chromatin (chromomeres). The chromomeres contain most of the chromosomal ENA which, along with histone, is tightly compacted as regular arrays of DNP. Many RNA transcripts are generated on the lateral loops, and heterogeneous non-histone proteins associate with these transcripts, forming periodic condensates of 20--30 nm ribonucleoprotein (RNP) particles. These unit particles aggregate in various ways and to varying degrees and thereby confer distinctive gross morphologies to particular loops. There are about 10(4) lateral loops per haploid complement of newt chromosomes and this figure is similar to the experimentally derived number of different messenger RNA sequences found in oocytes. From cytological and biochemical studies it is now possible to consider individual lateral loops from various aspects: as morphologically distinct units; as units of inheritance; as units of functional activity; as units of transcription; as units of transcribed repetitive sequences; and as units containing one coding sequence. The difficulties in arriving at a simple explanation of the organization of transcription in lampbrush chromosomes are discussed.", "contents": "The organization of transcription on lampbrush chromosomes. The meiotic lampbrush chromosomes of amphibian oocytes display readily distinguishable regions of transcription (lateral loops) which extend from axial condensates of chromatin (chromomeres). The chromomeres contain most of the chromosomal ENA which, along with histone, is tightly compacted as regular arrays of DNP. Many RNA transcripts are generated on the lateral loops, and heterogeneous non-histone proteins associate with these transcripts, forming periodic condensates of 20--30 nm ribonucleoprotein (RNP) particles. These unit particles aggregate in various ways and to varying degrees and thereby confer distinctive gross morphologies to particular loops. There are about 10(4) lateral loops per haploid complement of newt chromosomes and this figure is similar to the experimentally derived number of different messenger RNA sequences found in oocytes. From cytological and biochemical studies it is now possible to consider individual lateral loops from various aspects: as morphologically distinct units; as units of inheritance; as units of functional activity; as units of transcription; as units of transcribed repetitive sequences; and as units containing one coding sequence. The difficulties in arriving at a simple explanation of the organization of transcription in lampbrush chromosomes are discussed."}
{"id": "PMID:26087", "title": "The 75 S RNA transcription unit in Balbiani ring 2 and its relation to chromosome structure.", "content": "A defined transcription unit in the Balbiani ring 2 (BR 2) region of chromosome IV in the salivary glands of Chironomus tentans has been characterized on the basis of analysis of the corresponding primary transcript, 75S RNA, and its functional significance. The available information on the transcription unit and its relations to chromosome structure can be summarized in the following way: 1. The size of the 75S RNA transcription unit in BR 2 is on the order of 30 000 base pairs. 2. The unit is likely to contain a long coding segment (at least 6000 base pairs), probably corresponding to information for salivary polypeptides. 3. The sequences are distributed in more than one chromomere (probably in 3--5 chromomeres). Further studies are needed before it can be stated whether or not there is a simple one-to-one relation between chromomeres and transcription units in the BR 2 region.", "contents": "The 75 S RNA transcription unit in Balbiani ring 2 and its relation to chromosome structure. A defined transcription unit in the Balbiani ring 2 (BR 2) region of chromosome IV in the salivary glands of Chironomus tentans has been characterized on the basis of analysis of the corresponding primary transcript, 75S RNA, and its functional significance. The available information on the transcription unit and its relations to chromosome structure can be summarized in the following way: 1. The size of the 75S RNA transcription unit in BR 2 is on the order of 30 000 base pairs. 2. The unit is likely to contain a long coding segment (at least 6000 base pairs), probably corresponding to information for salivary polypeptides. 3. The sequences are distributed in more than one chromomere (probably in 3--5 chromomeres). Further studies are needed before it can be stated whether or not there is a simple one-to-one relation between chromomeres and transcription units in the BR 2 region."}
{"id": "PMID:26088", "title": "Heat shock of Drosophila melanogaster induces the synthesis of new messenger RNAs and proteins.", "content": "The heat shock proteins, labelled in vivo with [35S]methionine, were separated by sodium dodecylsulphate-polyacrylamide gel electrophoresis and fingerprinted after tryptic digestion. Eight distinct heat shock polypeptides are characterized in this way. Heat shock messenger RNAs were isolated and partially purified. Assayed in vitro for protein synthesis, they were found to code for heat shock polypeptides. Some parameters of the kinetics of in vivo synthesis of the heat shock proteins are presented.", "contents": "Heat shock of Drosophila melanogaster induces the synthesis of new messenger RNAs and proteins. The heat shock proteins, labelled in vivo with [35S]methionine, were separated by sodium dodecylsulphate-polyacrylamide gel electrophoresis and fingerprinted after tryptic digestion. Eight distinct heat shock polypeptides are characterized in this way. Heat shock messenger RNAs were isolated and partially purified. Assayed in vitro for protein synthesis, they were found to code for heat shock polypeptides. Some parameters of the kinetics of in vivo synthesis of the heat shock proteins are presented."}
{"id": "PMID:26090", "title": "Transcription in the interbands of Drosophila.", "content": "Many interbands of Drosophila contain morphological evidence for transcription. Decondensed band material makes no detectable contribution to certain transcriptionally active interbands.", "contents": "Transcription in the interbands of Drosophila. Many interbands of Drosophila contain morphological evidence for transcription. Decondensed band material makes no detectable contribution to certain transcriptionally active interbands."}
{"id": "PMID:26094", "title": "Antihypertensive drugs and depression: a reappraisal.", "content": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "contents": "Antihypertensive drugs and depression: a reappraisal. Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories."}
{"id": "PMID:26095", "title": "The behavioural actions of the hypothalamic peptides: a review.", "content": "Recent work has shown that the hypothalamic peptides commonly associated with the control of pituitary function have important behavioural actions of possible psychiatric significance. Thus, vasopressin, ACTH and like peptides may influence memory processes, and ACTH and MSH given intracranially induce a peculiar stretching and yawning syndrome accompanied by penile erection and ejaculation. Thyrotrophic hormone-releasing factor potentiates behavioural excitation, somatostatin is depressive, while luteinizing hormone-releasing hormone facilitates sexual behaviour and the newly identified endorphins are markedly opioid in character. These and other activities of the hypothalamic peptides are reviewed and assessed alongside the clinical information available.", "contents": "The behavioural actions of the hypothalamic peptides: a review. Recent work has shown that the hypothalamic peptides commonly associated with the control of pituitary function have important behavioural actions of possible psychiatric significance. Thus, vasopressin, ACTH and like peptides may influence memory processes, and ACTH and MSH given intracranially induce a peculiar stretching and yawning syndrome accompanied by penile erection and ejaculation. Thyrotrophic hormone-releasing factor potentiates behavioural excitation, somatostatin is depressive, while luteinizing hormone-releasing hormone facilitates sexual behaviour and the newly identified endorphins are markedly opioid in character. These and other activities of the hypothalamic peptides are reviewed and assessed alongside the clinical information available."}
{"id": "PMID:26096", "title": "Factor analysis of a sleep evaluation questionnaire.", "content": "A self-completion sleep evaluation questionnaire (SEQ), consisting of 10 cm line analogue rating scale questions, was constructed to investigate subjects' responses to aspects of sleep and early morning behaviour. The questions were grouped into 4 chronological areas: the ease of getting to sleep (GTS), the perceived quality of sleep (QOS), the ease of awakening from sleep (AFS), and the integrity of early morning behaviour following wakefulness (BFW). Five hundred and one SEQs were completed during several investigations into the comparative effectiveness of hypnotic drugs. The classical factor analysis produced 4 factors which corresponded to the 4 aspects of sleep and early morning behaviour listed above. The GTS and QOS factors were positively correlated (+0.57), as were the AFS and BFW factors (+0.48). The 2 sleeping state factors (GTS and QOS) were orthogonal to the 2 waking state factors (AFS and BFW).", "contents": "Factor analysis of a sleep evaluation questionnaire. A self-completion sleep evaluation questionnaire (SEQ), consisting of 10 cm line analogue rating scale questions, was constructed to investigate subjects' responses to aspects of sleep and early morning behaviour. The questions were grouped into 4 chronological areas: the ease of getting to sleep (GTS), the perceived quality of sleep (QOS), the ease of awakening from sleep (AFS), and the integrity of early morning behaviour following wakefulness (BFW). Five hundred and one SEQs were completed during several investigations into the comparative effectiveness of hypnotic drugs. The classical factor analysis produced 4 factors which corresponded to the 4 aspects of sleep and early morning behaviour listed above. The GTS and QOS factors were positively correlated (+0.57), as were the AFS and BFW factors (+0.48). The 2 sleeping state factors (GTS and QOS) were orthogonal to the 2 waking state factors (AFS and BFW)."}
{"id": "PMID:26098", "title": "Some altered responses in rats formerly dependent on morphine.", "content": "The investigation examined whether or not physical dependence or other abnormalities were detectable 1--3 months after withdrawal in dependent rats that had been treated with the morphine (amintenance dose of 100 X 2 mg/kg/day, s.c.) for 7 weeks. When narcotic antagonists were administered on the 32nd day after withdrawal, nalorphine caused a dose-dependent increase in spontaneous locomotor activity and a complete inhibition of wet-dog shakes and the writhing syndrome. Naloxone was ineffective. A remarkable increase in spontaneous locomotor activity on the 67th day and a significant increase in body weight on the 69th and 92nd day after withdrawal occurred after an acute injection of morphine (10 mg/kg, s.c.). When morphine (10 mg/kg) was administered for 3 days from the 92nd day after withdrawal, withdrawal from morphine produced a significant decrease in body weight. When morphine (10 mg/kg) was administered for 3 days from the 102nd day after withdrawal, a levallorphan injection caused a significant decrease in spontaneous locomotor activity and an increase in the frequency of the diarrheal syndrome. These abnormal responses, not observed in the naive rats, suggest the remains of some behavioral and biochemical abnormalities 3 months after morphine withdrawal.", "contents": "Some altered responses in rats formerly dependent on morphine. The investigation examined whether or not physical dependence or other abnormalities were detectable 1--3 months after withdrawal in dependent rats that had been treated with the morphine (amintenance dose of 100 X 2 mg/kg/day, s.c.) for 7 weeks. When narcotic antagonists were administered on the 32nd day after withdrawal, nalorphine caused a dose-dependent increase in spontaneous locomotor activity and a complete inhibition of wet-dog shakes and the writhing syndrome. Naloxone was ineffective. A remarkable increase in spontaneous locomotor activity on the 67th day and a significant increase in body weight on the 69th and 92nd day after withdrawal occurred after an acute injection of morphine (10 mg/kg, s.c.). When morphine (10 mg/kg) was administered for 3 days from the 92nd day after withdrawal, withdrawal from morphine produced a significant decrease in body weight. When morphine (10 mg/kg) was administered for 3 days from the 102nd day after withdrawal, a levallorphan injection caused a significant decrease in spontaneous locomotor activity and an increase in the frequency of the diarrheal syndrome. These abnormal responses, not observed in the naive rats, suggest the remains of some behavioral and biochemical abnormalities 3 months after morphine withdrawal."}
{"id": "PMID:26099", "title": "Comparison studies of chlorazepate administered as a divided daily dose and as a single dose at night.", "content": "The residual effects of dipotassium chlorazepate administered as either a single daily dose of 20 mg at bedtime or a divided daily dose (5 + 5 + 10 mg) were studied in a placebo-controlled, double-blind trial comprising 12 out-patients. The following tests were used to determine changes in perceptual wakefulness, performance ability, fine motor skills, and coordination: critical flicker fusion test, car driving in a simulator, and the \"bead and needle tests.\" In addition, the patients underwent a clinical assessment and also filled out a self-rating scale for judging factors related to the tests. No significant differences were found between the dosage schedules or between the active medication and the placebo. The clinical results were not dependent on the dosage schedule.", "contents": "Comparison studies of chlorazepate administered as a divided daily dose and as a single dose at night. The residual effects of dipotassium chlorazepate administered as either a single daily dose of 20 mg at bedtime or a divided daily dose (5 + 5 + 10 mg) were studied in a placebo-controlled, double-blind trial comprising 12 out-patients. The following tests were used to determine changes in perceptual wakefulness, performance ability, fine motor skills, and coordination: critical flicker fusion test, car driving in a simulator, and the \"bead and needle tests.\" In addition, the patients underwent a clinical assessment and also filled out a self-rating scale for judging factors related to the tests. No significant differences were found between the dosage schedules or between the active medication and the placebo. The clinical results were not dependent on the dosage schedule."}
{"id": "PMID:26100", "title": "A survey study of the use of electropupillogram in predicting response to psychostimulants.", "content": "To confirm the conclusions from a previous study supporting the usefullness of electropupillogram (E.P.G.) in predicting clinical response, data from three separate studies with hyperkinetic and learning disabled (L.D.) children treated with stimulants were surveyed. Change in extent of pupillary contraction (E.C.) after a test dose of stimulant as measured by E.P.G. did not correlate significantly with actual clinical rating change (with one exception out of 14 correlations calculated). These negative results are reported with a reservation regarding their validity because of technical difficulties in data collection.", "contents": "A survey study of the use of electropupillogram in predicting response to psychostimulants. To confirm the conclusions from a previous study supporting the usefullness of electropupillogram (E.P.G.) in predicting clinical response, data from three separate studies with hyperkinetic and learning disabled (L.D.) children treated with stimulants were surveyed. Change in extent of pupillary contraction (E.C.) after a test dose of stimulant as measured by E.P.G. did not correlate significantly with actual clinical rating change (with one exception out of 14 correlations calculated). These negative results are reported with a reservation regarding their validity because of technical difficulties in data collection."}
{"id": "PMID:26101", "title": "Neuroleptic drugs block both the hyperactivity and the increase in caudate nucleus cyclic AMP concentration produced by the administration of tranylcypromine and L-dopa to rats.", "content": "Injection of rats with tranylcypromine and L-dopa increased brain dopamine concentrations and produced a behavioural syndrome that includes hyperactivity. It also elevated caudate nucleus cyclic AMP concentrations by approximately 50% in vivo, probably by stimulating dopamine receptors. Pretreatment with chlorpromazine inhibited both the tranylcypromine/L-dopa-induced behaviour and elevated cyclic AMP concentrations in a dose-dependent manner. Haloperidol and alpha-flupenthixol also inhibited both effects, while beta-flupenthixol and pimozide were without effect. Since none of these drugs altered the tranylcypromine/L-dopa-induced rise of brain dopamine, it is likely that they produced their effect by inhibiting dopamine-sensitive adenylate cyclase. A good correlation was found to exist between the neuroleptic inhibition of both the increased behavioural activity and the increased caudate nucleus cyclic AMP concentrations produced by tranylcypromine and L-dopa.", "contents": "Neuroleptic drugs block both the hyperactivity and the increase in caudate nucleus cyclic AMP concentration produced by the administration of tranylcypromine and L-dopa to rats. Injection of rats with tranylcypromine and L-dopa increased brain dopamine concentrations and produced a behavioural syndrome that includes hyperactivity. It also elevated caudate nucleus cyclic AMP concentrations by approximately 50% in vivo, probably by stimulating dopamine receptors. Pretreatment with chlorpromazine inhibited both the tranylcypromine/L-dopa-induced behaviour and elevated cyclic AMP concentrations in a dose-dependent manner. Haloperidol and alpha-flupenthixol also inhibited both effects, while beta-flupenthixol and pimozide were without effect. Since none of these drugs altered the tranylcypromine/L-dopa-induced rise of brain dopamine, it is likely that they produced their effect by inhibiting dopamine-sensitive adenylate cyclase. A good correlation was found to exist between the neuroleptic inhibition of both the increased behavioural activity and the increased caudate nucleus cyclic AMP concentrations produced by tranylcypromine and L-dopa."}
{"id": "PMID:26109", "title": "Labilization of brain lysosomes by trichloroethylene metabolites and peroxide anion in vitro.", "content": "Lysosomes were isolated from adult male Wistar rat brain and incubated in vitro with 10 micron trichloroethylene and microsomes or postmicrosomal supernatant with added NADPH. Freezing and incubation with the solvent alone served as controls. The results were compared with the effect of peroxide anion from the xanthine-xanthine oxidase reaction. Mere solvent did not cause an appearance of acid proteinase activity in the incubation medium whereas other treatments induced lysosomal labilization.", "contents": "Labilization of brain lysosomes by trichloroethylene metabolites and peroxide anion in vitro. Lysosomes were isolated from adult male Wistar rat brain and incubated in vitro with 10 micron trichloroethylene and microsomes or postmicrosomal supernatant with added NADPH. Freezing and incubation with the solvent alone served as controls. The results were compared with the effect of peroxide anion from the xanthine-xanthine oxidase reaction. Mere solvent did not cause an appearance of acid proteinase activity in the incubation medium whereas other treatments induced lysosomal labilization."}
{"id": "PMID:26110", "title": "Changes in plasma high density lipoproteins in chronic male alcoholics during and after abuse.", "content": "Alterations in plasma high density lipoproteins (HDL) were studied in thirty-eight male chronic alcoholics. Twenty-four (63%) of the patients had increased HDL protein (measured immunochemically) and twenty-five (66%) had increased HDL cholesterol (determined after polyanion precipitation of very low density lipoproteins (VLDL) and low density lipoproteins (LDL)). A statistically significant correlation was found between HDL protein and HDL cholesterol (r = 0.39). gamma-Glutamyltransferase (GT) was elevated in eighteen (47%) of the alcoholics. No significant correlations were found between GT and HDL protein or HDL cholesterol. The increase in HDL, as studied by rate zonal ultracentrifugation, was heterogeneous with changes in the HDL2 as well as HDL3 subfractions. It is suggested that determination of HDL total cholesterol, in combination with GT, may represent a valuable and sensitive test for detection of alcoholism.", "contents": "Changes in plasma high density lipoproteins in chronic male alcoholics during and after abuse. Alterations in plasma high density lipoproteins (HDL) were studied in thirty-eight male chronic alcoholics. Twenty-four (63%) of the patients had increased HDL protein (measured immunochemically) and twenty-five (66%) had increased HDL cholesterol (determined after polyanion precipitation of very low density lipoproteins (VLDL) and low density lipoproteins (LDL)). A statistically significant correlation was found between HDL protein and HDL cholesterol (r = 0.39). gamma-Glutamyltransferase (GT) was elevated in eighteen (47%) of the alcoholics. No significant correlations were found between GT and HDL protein or HDL cholesterol. The increase in HDL, as studied by rate zonal ultracentrifugation, was heterogeneous with changes in the HDL2 as well as HDL3 subfractions. It is suggested that determination of HDL total cholesterol, in combination with GT, may represent a valuable and sensitive test for detection of alcoholism."}
{"id": "PMID:26111", "title": "Evidence for two types of non-specific suppressor cells activated by the graft-versus-host reaction in mice.", "content": "In vitro experiments were carried out to investigate the immunosuppressive efect of different populations of spleen cells obtained from animal experiencing a graft-versus-host reaction (GVHR). To induce the GVHR, parental lymphoid cells were injected into adult F1 hybrid mice. GVHR-activated spleen cells (GVH-sc) taken at different times post-GVHR induction were separated into adherent and non-adherent fractions and treated with anti-theta serum plus complement. The different types of GVH-SC were added to either parental (donor-type) of F1 (host-type) normal spleen cells and cultured with sheep erythrocytes in a modified Marbrook chamber. It was found that both adherent and non-adherent 10-day GVH-SC significantly inhibited the plaque-forming cell response of F1 normal spleen cells but not that of parental normal spleen cells. Significant suppression of the parental response was observed following the addition of 15-day GVH-SC or anti-theta treated adherent and non-adherent 7-day GVH-SC. The results suggest that the non-specific immunosuppressive effect of GVH-SC is mediated by GVHR-activated macrophages and B lymphocytes found in the anti-theta treated adherent and non-adherent fractions of the GVH-SC suspensions respectively.", "contents": "Evidence for two types of non-specific suppressor cells activated by the graft-versus-host reaction in mice. In vitro experiments were carried out to investigate the immunosuppressive efect of different populations of spleen cells obtained from animal experiencing a graft-versus-host reaction (GVHR). To induce the GVHR, parental lymphoid cells were injected into adult F1 hybrid mice. GVHR-activated spleen cells (GVH-sc) taken at different times post-GVHR induction were separated into adherent and non-adherent fractions and treated with anti-theta serum plus complement. The different types of GVH-SC were added to either parental (donor-type) of F1 (host-type) normal spleen cells and cultured with sheep erythrocytes in a modified Marbrook chamber. It was found that both adherent and non-adherent 10-day GVH-SC significantly inhibited the plaque-forming cell response of F1 normal spleen cells but not that of parental normal spleen cells. Significant suppression of the parental response was observed following the addition of 15-day GVH-SC or anti-theta treated adherent and non-adherent 7-day GVH-SC. The results suggest that the non-specific immunosuppressive effect of GVH-SC is mediated by GVHR-activated macrophages and B lymphocytes found in the anti-theta treated adherent and non-adherent fractions of the GVH-SC suspensions respectively."}
{"id": "PMID:26113", "title": "The rapidity of bronchodilatation. A comparison of isoprenaline, terbutaline and rimiterol.", "content": "The onset of action of three sympathomimetic drugs (rimiterol 0.2 mg, terbutaline 0.25 mg and isoprenaline 0.08 mg) administered by metered dose inhaler was compared in 12 asthmatics. In order to evaluate side effects of the drugs, a second dose of the aerosols, 8-10 times higher than the first one, was given after 30 min. The effects were measured in terms of VC, FEV1.0, PEF and heart rate. All the substances caused a significant increase in spirometric values within 1.5 min, the results with isoprenaline being slightly better than those with terbutaline. An increased heart rate was observed after the first dose of isoprenaline whereas no further increase was found after the higher dose. Two patients complained of palpitations, one after isoprenaline and one after rimiterol. No other side effects were recorded. It is concluded that there is a small, clinically insignificant, difference in the onset of action of isoprenaline compared with that of the selective beta2-stimulating aerosol, terbutaline.", "contents": "The rapidity of bronchodilatation. A comparison of isoprenaline, terbutaline and rimiterol. The onset of action of three sympathomimetic drugs (rimiterol 0.2 mg, terbutaline 0.25 mg and isoprenaline 0.08 mg) administered by metered dose inhaler was compared in 12 asthmatics. In order to evaluate side effects of the drugs, a second dose of the aerosols, 8-10 times higher than the first one, was given after 30 min. The effects were measured in terms of VC, FEV1.0, PEF and heart rate. All the substances caused a significant increase in spirometric values within 1.5 min, the results with isoprenaline being slightly better than those with terbutaline. An increased heart rate was observed after the first dose of isoprenaline whereas no further increase was found after the higher dose. Two patients complained of palpitations, one after isoprenaline and one after rimiterol. No other side effects were recorded. It is concluded that there is a small, clinically insignificant, difference in the onset of action of isoprenaline compared with that of the selective beta2-stimulating aerosol, terbutaline."}
{"id": "PMID:26114", "title": "[Role of metabolites in the relationship between pharmacokinetics and the effect of beta blockers. Studies on tolamolol and bufuralol].", "content": "Plasma concentrations of tolamolol and bufuralol (beta-blocking agents) were measured after oral and intravenous administration to healthy volunteers. The plasma levels of their main metabolite was also determined. Simultaneously, the effect of the drugs on the heart rate and blood pressure was monitored under various stimuli (isoproterenol, exercise or orthostatism) and Valsalva maneuver. When given orally, the two drugs are extensively metabolized by a hepatic first-pass effect. After reaching the systemic circulation, they are metabolized in the liver to hydroxylated derivatives with similar pharmacologic activity as the parent molecule. For tolamolol it is possible to demonstrate a good correlation between parent drug blood levels and the pharmacodynamic effect; this relation is less evident for bufuralol. The pharmacokinetic analysis of the behaviour of the two beta-blocking agents and their main metabolite makes it possible to explain this difference in part. The results of the present study emphasize the importance of measuring metabolites when dose-action relationships are investigated.", "contents": "[Role of metabolites in the relationship between pharmacokinetics and the effect of beta blockers. Studies on tolamolol and bufuralol]. Plasma concentrations of tolamolol and bufuralol (beta-blocking agents) were measured after oral and intravenous administration to healthy volunteers. The plasma levels of their main metabolite was also determined. Simultaneously, the effect of the drugs on the heart rate and blood pressure was monitored under various stimuli (isoproterenol, exercise or orthostatism) and Valsalva maneuver. When given orally, the two drugs are extensively metabolized by a hepatic first-pass effect. After reaching the systemic circulation, they are metabolized in the liver to hydroxylated derivatives with similar pharmacologic activity as the parent molecule. For tolamolol it is possible to demonstrate a good correlation between parent drug blood levels and the pharmacodynamic effect; this relation is less evident for bufuralol. The pharmacokinetic analysis of the behaviour of the two beta-blocking agents and their main metabolite makes it possible to explain this difference in part. The results of the present study emphasize the importance of measuring metabolites when dose-action relationships are investigated."}
{"id": "PMID:26130", "title": "Graft-versus-host reactions within the thyroid gland may evoke pari passu autoimmune thyroiditis.", "content": "Unilateral, intraorganal injection of parental lymph node cells into thyroid lobes of F1 hybrid rats elicited an intense, local graft-versus-host reaction within the injected lobes containing massive numbers of lymphocytes. Surprisingly, significant mononuclear cell infiltration was also seen within the contralateral (noninjected) thyroid lobes, even when the isthmus had been divided. The local graft-versus-host reaction spread from the injected gland to involve the regional lymph nodes and spleen. Migration of 51-cr-labeled donor lymph node cells was documented in these same tissue sites; lesser numbers of labeled cells were found in distant lymph nodes, including the contralateral cervical nodes. However, no significant label was found in the contralateral thyroid lobes. Microscopic evaluation of noninjected glands revealed intense infiltration of mononuclear cells around and within follicles, reminiscent of lesions induced by immunization with thyroid extract in Freund's complete adjuvant. The absence of donor cells in the inflammatory reactions within noninjected thyroid lobes raises the possibility of an autoimmune rather than graft-versus-host pathogenesis.", "contents": "Graft-versus-host reactions within the thyroid gland may evoke pari passu autoimmune thyroiditis. Unilateral, intraorganal injection of parental lymph node cells into thyroid lobes of F1 hybrid rats elicited an intense, local graft-versus-host reaction within the injected lobes containing massive numbers of lymphocytes. Surprisingly, significant mononuclear cell infiltration was also seen within the contralateral (noninjected) thyroid lobes, even when the isthmus had been divided. The local graft-versus-host reaction spread from the injected gland to involve the regional lymph nodes and spleen. Migration of 51-cr-labeled donor lymph node cells was documented in these same tissue sites; lesser numbers of labeled cells were found in distant lymph nodes, including the contralateral cervical nodes. However, no significant label was found in the contralateral thyroid lobes. Microscopic evaluation of noninjected glands revealed intense infiltration of mononuclear cells around and within follicles, reminiscent of lesions induced by immunization with thyroid extract in Freund's complete adjuvant. The absence of donor cells in the inflammatory reactions within noninjected thyroid lobes raises the possibility of an autoimmune rather than graft-versus-host pathogenesis."}
{"id": "PMID:26136", "title": "[Risk of surgery at the height of a gastroduodenal hemorrhage].", "content": "The authors believe that the decrease of mortality in operations for gastroduodenal bleeding does not depend on the time interval between the start of bleeding and surgical interventions, but it depends upon the conditions under which these interventions are carried out. The conditions should approximate the conditions existing in planned gastric surgery as much as possible. In this regard the results of the treatment of 188 cases with massive gastroduodenal bleeding (69 cases aged over 60) are analyzed. The applied method permitted to ensure a sufficient volume of the examination of a case and of his preparation to the operation to avoid \"desperate operations\" and to decrease considerably the mortality in gastroduodenal bleeding. Among patients under 65 there were no fatal cases.", "contents": "[Risk of surgery at the height of a gastroduodenal hemorrhage]. The authors believe that the decrease of mortality in operations for gastroduodenal bleeding does not depend on the time interval between the start of bleeding and surgical interventions, but it depends upon the conditions under which these interventions are carried out. The conditions should approximate the conditions existing in planned gastric surgery as much as possible. In this regard the results of the treatment of 188 cases with massive gastroduodenal bleeding (69 cases aged over 60) are analyzed. The applied method permitted to ensure a sufficient volume of the examination of a case and of his preparation to the operation to avoid \"desperate operations\" and to decrease considerably the mortality in gastroduodenal bleeding. Among patients under 65 there were no fatal cases."}
{"id": "PMID:26139", "title": "[Haemodynamic characterization of a new beta-receptor blocker celiprolol (st1396) at rest and during ergometer exercise compared with propranolol (inderal) (author's transl)].", "content": "A new beta-receptor blocker (Celiprolol) was characterized in man by haemodynamic studies carried out on a random cross-over basis in 6 volunteers before and after intravenous administration of the drug or propranolol. The studies were performed at rest and in response to ergometer exercise. The studies showed that: 1. Celiprolol is a cardio-selective beta-receptor blocker with pronounced intrinsic sympathomimetic activity. Hence, Celiprolol increases the heart rate and cardiac output at rest. 2. The heart rate was reduced by Celiprolol during pronounced physical exercise. 3. Celiprolol probably has only a very slight blocking effect on those, beta1-receptors which mediate a positive inotropic effect. 4. The increase in blood pressure during exercise was less pronounced during Celiprolol medication than with propranolol.", "contents": "[Haemodynamic characterization of a new beta-receptor blocker celiprolol (st1396) at rest and during ergometer exercise compared with propranolol (inderal) (author's transl)]. A new beta-receptor blocker (Celiprolol) was characterized in man by haemodynamic studies carried out on a random cross-over basis in 6 volunteers before and after intravenous administration of the drug or propranolol. The studies were performed at rest and in response to ergometer exercise. The studies showed that: 1. Celiprolol is a cardio-selective beta-receptor blocker with pronounced intrinsic sympathomimetic activity. Hence, Celiprolol increases the heart rate and cardiac output at rest. 2. The heart rate was reduced by Celiprolol during pronounced physical exercise. 3. Celiprolol probably has only a very slight blocking effect on those, beta1-receptors which mediate a positive inotropic effect. 4. The increase in blood pressure during exercise was less pronounced during Celiprolol medication than with propranolol."}
{"id": "PMID:26142", "title": "[Experimental study concerning the psychological preparation to parturition (author's transl)].", "content": "The following study reports an application to primae gravidae of two different psychological treatments aiming at reducing the fear of childbearing and facilitating the delivery. The treatments under comparison were systematic desensitization and modification of self instruction, a more cognitive approach. The effects of the two treatments proved to be identical; nevertheless there were significant differences between the results of the women who underwent treatment and those of the control group. Moreover, in our study a certain  number of socioeconomic factors turned out to be correlated with the treatment effects.", "contents": "[Experimental study concerning the psychological preparation to parturition (author's transl)]. The following study reports an application to primae gravidae of two different psychological treatments aiming at reducing the fear of childbearing and facilitating the delivery. The treatments under comparison were systematic desensitization and modification of self instruction, a more cognitive approach. The effects of the two treatments proved to be identical; nevertheless there were significant differences between the results of the women who underwent treatment and those of the control group. Moreover, in our study a certain  number of socioeconomic factors turned out to be correlated with the treatment effects."}
{"id": "PMID:26155", "title": "[The influence on efficacy of formaldehyd and phenol against bacterial cells I. Effect of drying, cations and pH-value (author's transl)].", "content": "1. When cells of E. coli and Staph. aureus are dried, the efficacy of phenol is reduced but the efficacy of formaldehyde is increased. 2. A change of the aw-value by addition of salts changes the efficacy of formaldehyde as well as that of phenol. For these tests the chlorides of various alkali and alkaline earth metals were used in different concentrations. 3. The optimal efficacy of phenol and formaldehyde within the tested concentration gradientis caused by different concentrations of the ions: In low concentrations the efficacy of formaldehyde is optimally increased, the efficacy of phenol, however, attains a minimum at this concentration range. By higher concentrations of ions the efficacy of phenol is increased, that of formaldehyde is reduced. 4. The position of the cations in the periodic system also plays a role in the influence on the efficacy of the phenol and formaldehyde respectively. The cations of the lower periods from the main groups I and II favour the damage to the cells by phenol, the cations of the higher periods favour the damage by formaldehyde.", "contents": "[The influence on efficacy of formaldehyd and phenol against bacterial cells I. Effect of drying, cations and pH-value (author's transl)]. 1. When cells of E. coli and Staph. aureus are dried, the efficacy of phenol is reduced but the efficacy of formaldehyde is increased. 2. A change of the aw-value by addition of salts changes the efficacy of formaldehyde as well as that of phenol. For these tests the chlorides of various alkali and alkaline earth metals were used in different concentrations. 3. The optimal efficacy of phenol and formaldehyde within the tested concentration gradientis caused by different concentrations of the ions: In low concentrations the efficacy of formaldehyde is optimally increased, the efficacy of phenol, however, attains a minimum at this concentration range. By higher concentrations of ions the efficacy of phenol is increased, that of formaldehyde is reduced. 4. The position of the cations in the periodic system also plays a role in the influence on the efficacy of the phenol and formaldehyde respectively. The cations of the lower periods from the main groups I and II favour the damage to the cells by phenol, the cations of the higher periods favour the damage by formaldehyde."}
{"id": "PMID:26158", "title": "Changes in gastric secretion following administration of preparations affecting the parasympathetic and sympathetic nervous system.", "content": "The changes in gastric secretion following administration of different preparations have been studied in  a group of 180 patients with duodenal ulcer and chronic gastritis. In patients with hypersecretion the medication with bishpan and inderal as compared with atropine caused considerable shifts in the indices of gastric secretion. Isoproterenol exerted a stimulating influence both on initial hyper- and hyposecretion, while the other preparations studied were shown not to cause any essential rise in gastric secretion in patients with secretory deficiency. Reliable changes of the stimulated gastric secretion were observed only after inderal. The data obtained can be useful when choosing a rational method for the therapy of gastric scretory disorders.", "contents": "Changes in gastric secretion following administration of preparations affecting the parasympathetic and sympathetic nervous system. The changes in gastric secretion following administration of different preparations have been studied in  a group of 180 patients with duodenal ulcer and chronic gastritis. In patients with hypersecretion the medication with bishpan and inderal as compared with atropine caused considerable shifts in the indices of gastric secretion. Isoproterenol exerted a stimulating influence both on initial hyper- and hyposecretion, while the other preparations studied were shown not to cause any essential rise in gastric secretion in patients with secretory deficiency. Reliable changes of the stimulated gastric secretion were observed only after inderal. The data obtained can be useful when choosing a rational method for the therapy of gastric scretory disorders."}
{"id": "PMID:26159", "title": "Cardiovascular effects of local adrenaline infiltration during halothane anaesthesia and adrenergic beta-receptor blockade in man.", "content": "Adrenergic beta-receptor blocking agents, alprenolol, propranolol and practolol were given as a prophylactic measure to patients undergoing middle-ear microsurgery where adrenaline was deliberately infiltrated during halothane-N2O/O2 anaesthesia. These three beta blockers did not differ in their action on heart rate, arterial blood pressure, right ventricular pressure, CVP or peripheral pulse wave in equipotent doses, which were 0.04 mg/kg for alprenolol and propranolol and 0.4 mg/kg for practolol in this study. Atropine caused a highly significant increase in heart rate in the spontaneously ventilating group and maintained blood pressure at higher levels, although the latter difference was not significant. Alprenolol and propranolol offered partial protection for over 40 min against adrenaline-induced arrhythmias. Occasionally occuring tachyarrhythmias were easily terminated with a further dose of a beta blocker. The effective half-life of practolol was less than 15 min and doses up to 0.4 mg/kg were unable to prevent arrhythmias during adrenaline challenge.", "contents": "Cardiovascular effects of local adrenaline infiltration during halothane anaesthesia and adrenergic beta-receptor blockade in man. Adrenergic beta-receptor blocking agents, alprenolol, propranolol and practolol were given as a prophylactic measure to patients undergoing middle-ear microsurgery where adrenaline was deliberately infiltrated during halothane-N2O/O2 anaesthesia. These three beta blockers did not differ in their action on heart rate, arterial blood pressure, right ventricular pressure, CVP or peripheral pulse wave in equipotent doses, which were 0.04 mg/kg for alprenolol and propranolol and 0.4 mg/kg for practolol in this study. Atropine caused a highly significant increase in heart rate in the spontaneously ventilating group and maintained blood pressure at higher levels, although the latter difference was not significant. Alprenolol and propranolol offered partial protection for over 40 min against adrenaline-induced arrhythmias. Occasionally occuring tachyarrhythmias were easily terminated with a further dose of a beta blocker. The effective half-life of practolol was less than 15 min and doses up to 0.4 mg/kg were unable to prevent arrhythmias during adrenaline challenge."}
{"id": "PMID:26160", "title": "Cardiovascular effects of local adrenaline infiltration during neurolept analgesia and adrenergic beta-receptor blockade in man.", "content": "The adrenergic beta-receptor blocking drug, alprenolol, was given together with atropine to 15 patients during neurolept analgesia (NLA) in order to prevent adrenaline-induced cardiac arrhythmias. Four patients operated on without adrenergic beta-receptor blockade formed the control group. Three of them developed tachyarrhythmias, ventricular tachycardia, multifocal ventricular extrasystoles and supraventricular tachycardia. All these arrhythmias were terminated by the adrenergic beta-receptor blocking drug, propranolol. The fourth patient developed a temporary sinus tachycardia which did not require any treatment. The adrenergic beta-receptor blockade induced a slight increase in pulse rate with almost no change in arterial blood pressure. The incidence of arrhythmias due to adrenaline infiltration was much less in this group. There was one supraventricular tachycardia and scattered ventricular extrasystoles in two other patients. NLA alone does not protect the heart against adrenaline-induced arrhythmias. It does, however, seem to be compatible with an adrenergic beta-receptor blockade, which in turn provides partial protection against adrenaline-induced arrhythmias. The occasionally developing arrhythmias can then be terminated with specific adrenergic beta blockers.", "contents": "Cardiovascular effects of local adrenaline infiltration during neurolept analgesia and adrenergic beta-receptor blockade in man. The adrenergic beta-receptor blocking drug, alprenolol, was given together with atropine to 15 patients during neurolept analgesia (NLA) in order to prevent adrenaline-induced cardiac arrhythmias. Four patients operated on without adrenergic beta-receptor blockade formed the control group. Three of them developed tachyarrhythmias, ventricular tachycardia, multifocal ventricular extrasystoles and supraventricular tachycardia. All these arrhythmias were terminated by the adrenergic beta-receptor blocking drug, propranolol. The fourth patient developed a temporary sinus tachycardia which did not require any treatment. The adrenergic beta-receptor blockade induced a slight increase in pulse rate with almost no change in arterial blood pressure. The incidence of arrhythmias due to adrenaline infiltration was much less in this group. There was one supraventricular tachycardia and scattered ventricular extrasystoles in two other patients. NLA alone does not protect the heart against adrenaline-induced arrhythmias. It does, however, seem to be compatible with an adrenergic beta-receptor blockade, which in turn provides partial protection against adrenaline-induced arrhythmias. The occasionally developing arrhythmias can then be terminated with specific adrenergic beta blockers."}
{"id": "PMID:26162", "title": "Qualitative differences between beta-adrenergic and alpha-adrenergic inotropic effects in rat heart muscle.", "content": "If beta- and alpha-adrenergic inotropic effects are cyclic AMP dependent and cyclic AMP independent, respectively, they may be qualitatively different. The inotropic effects of beta-receptor stimulation (isoprenaline) and alpha-receptor stimulation (phenylephrine combined with propranolol) were characterized in isolated perfused rat hearts, rat atria and rat papillary muscles. The beta-effect reached its maximum before the alpha-effect. The alpha-effect followed a three-phasic time-course indicating both stimulatory and inhibitory components. The aortic pressure wave (perfused heart) indicated a shorter contraction phase after beta-stimulation than after alpha-stimulation. The time to peak tension (atrium, papillary muscle) was relatively shorter after isoprenaline than after alpha-stimulation, which tended to prolong it. The contraction-relaxation cycles (atrium, papillary muscle) were examined by recording the isometric tension (T), its first (T') and second (T'') deri derivatives. alpha and beta-stimulation both increased Tmax, T'max (maximal rate of tension rise), T'min (maximal rate of tension decline) and T''min (maximal rate of transition from rise to decline of tension). Isoprenaline increased T'min (papillary muscle) and T''min (atrium, papillary muscle) relatively more than did alpha-stimulation, i.e. the relaxing processes were activated relatively more by beta-stimulation. The results indicate different mechanisms for the two adrenergic inotropic effects. The relatively larger activation of relaxation by beta-stimulation is assumed to be caused by clic AMP.", "contents": "Qualitative differences between beta-adrenergic and alpha-adrenergic inotropic effects in rat heart muscle. If beta- and alpha-adrenergic inotropic effects are cyclic AMP dependent and cyclic AMP independent, respectively, they may be qualitatively different. The inotropic effects of beta-receptor stimulation (isoprenaline) and alpha-receptor stimulation (phenylephrine combined with propranolol) were characterized in isolated perfused rat hearts, rat atria and rat papillary muscles. The beta-effect reached its maximum before the alpha-effect. The alpha-effect followed a three-phasic time-course indicating both stimulatory and inhibitory components. The aortic pressure wave (perfused heart) indicated a shorter contraction phase after beta-stimulation than after alpha-stimulation. The time to peak tension (atrium, papillary muscle) was relatively shorter after isoprenaline than after alpha-stimulation, which tended to prolong it. The contraction-relaxation cycles (atrium, papillary muscle) were examined by recording the isometric tension (T), its first (T') and second (T'') deri derivatives. alpha and beta-stimulation both increased Tmax, T'max (maximal rate of tension rise), T'min (maximal rate of tension decline) and T''min (maximal rate of transition from rise to decline of tension). Isoprenaline increased T'min (papillary muscle) and T''min (atrium, papillary muscle) relatively more than did alpha-stimulation, i.e. the relaxing processes were activated relatively more by beta-stimulation. The results indicate different mechanisms for the two adrenergic inotropic effects. The relatively larger activation of relaxation by beta-stimulation is assumed to be caused by clic AMP."}
{"id": "PMID:26163", "title": "The effect of nifedipine on the sinus and atrioventricular node of the dog heart after beta-adrenergic receptor blockade.", "content": "The effect of nifedipine (BAY 1040), a calcium-antagonistic inhibitor of the electromechanical coupling process was tested on atrioventricular conduction and refractoriness of the dog heart in situ by means of His-bundle electrography and programmed electrical stimulation. The animals were anaesthetized with sodium pentobarbital. As the basic effects of the compound can be altered by release of catecholamines from sympathetic nerves of heart and vessels, the dogs were pretreated with acebutolol, a beta-adrenergic receptor blocking agent, which decreased heart rate and prolonged atrioventricular conduction and refractoriness. Nifedipine 1,6 and particularly 30 microgram/kg body weight increased the heart rate and decreased atrioventricular conduction time during atrial pacing, whereas atrioventricular conduction time during sinus rhythm and atrioventricular refractoriness were only affected by nifedipine 30 microgram/kg. In this respect, nifedipine differs distinctly from another calcium antagonistic compound, verapamil.", "contents": "The effect of nifedipine on the sinus and atrioventricular node of the dog heart after beta-adrenergic receptor blockade. The effect of nifedipine (BAY 1040), a calcium-antagonistic inhibitor of the electromechanical coupling process was tested on atrioventricular conduction and refractoriness of the dog heart in situ by means of His-bundle electrography and programmed electrical stimulation. The animals were anaesthetized with sodium pentobarbital. As the basic effects of the compound can be altered by release of catecholamines from sympathetic nerves of heart and vessels, the dogs were pretreated with acebutolol, a beta-adrenergic receptor blocking agent, which decreased heart rate and prolonged atrioventricular conduction and refractoriness. Nifedipine 1,6 and particularly 30 microgram/kg body weight increased the heart rate and decreased atrioventricular conduction time during atrial pacing, whereas atrioventricular conduction time during sinus rhythm and atrioventricular refractoriness were only affected by nifedipine 30 microgram/kg. In this respect, nifedipine differs distinctly from another calcium antagonistic compound, verapamil."}
{"id": "PMID:26164", "title": "Myocardial effects of lithium in vitro.", "content": "The myocardial effects of increasing concentrations of ionic lithium were investigated in isolated, spontaneously beating rabbit hearts, which were retrogradely perfused with a modified Krebs-Henseleit solution containing lithium in concentration of 1, 5 or 10 mM. The following functional parameters were continuously recorded: heart rate, amplitude and rate of contraction, coronary flow, myocardial oxygen consumption and ECG. The lowest concentration of 1 mM lithium did not cause any measurable changes in these parameters. A concentration of 5 mM lithium produced a rather slowly developed increase in amplitude and rate of contraction of about 22% without any concomitant increase of oxygen consumption. A delayed increase in the oxygen consumption of about 21%, but accompanied by a significant decrease in contractility however, occurred much later in the experiments, probably as an expression of a decrease in myocardial efficiency. The highest lithium concentration produced similar effects. None of the other parameters measured were markedly influenced by lithium. The positive inotropic effect of lithium on myocardial contractility was very convincingly verified in isolated electrically stimulated rabbit papillary muscles by isometric measurements of the maximum tension produced and the rate of its development. An inhibitory influence of lithium on the positive inotropic effect of increasing frequency of stimulation was observed. Adrenergic beta-receptor blockade did not abolish the positive inotropic effect of lithium. A possible causative influence of lithium on the cellular calcium metabolism is discussed.", "contents": "Myocardial effects of lithium in vitro. The myocardial effects of increasing concentrations of ionic lithium were investigated in isolated, spontaneously beating rabbit hearts, which were retrogradely perfused with a modified Krebs-Henseleit solution containing lithium in concentration of 1, 5 or 10 mM. The following functional parameters were continuously recorded: heart rate, amplitude and rate of contraction, coronary flow, myocardial oxygen consumption and ECG. The lowest concentration of 1 mM lithium did not cause any measurable changes in these parameters. A concentration of 5 mM lithium produced a rather slowly developed increase in amplitude and rate of contraction of about 22% without any concomitant increase of oxygen consumption. A delayed increase in the oxygen consumption of about 21%, but accompanied by a significant decrease in contractility however, occurred much later in the experiments, probably as an expression of a decrease in myocardial efficiency. The highest lithium concentration produced similar effects. None of the other parameters measured were markedly influenced by lithium. The positive inotropic effect of lithium on myocardial contractility was very convincingly verified in isolated electrically stimulated rabbit papillary muscles by isometric measurements of the maximum tension produced and the rate of its development. An inhibitory influence of lithium on the positive inotropic effect of increasing frequency of stimulation was observed. Adrenergic beta-receptor blockade did not abolish the positive inotropic effect of lithium. A possible causative influence of lithium on the cellular calcium metabolism is discussed."}
{"id": "PMID:26161", "title": "[Quantitative hyperpnea in EEG (author's transl)].", "content": "After summarizing the phenomena of respiratory physiology involved in the hyperpnea test, the author studies the quantitative relation between the drop in PECO2 (pressure of CO2 in expired air) and changes in the EEG during hyperpnea. Normal subjects are divided into two groups of a hundred (6 to 19 1/2 years of age; 20 to 59 1/2 years of age). The PECO2 at rest is higher among the young subjects than among the adults, and its decline during hyperpnea is sharper. Thus, children show discrete respiratory acidosis in comparison with adults. The EEG of normal adults is practically unchanged during hyperpnea whereas, in the young group, moderate changes in the profile were observed in 45 out of 100 cases (classified empirically as normal). The PECO2 reaches a lower level in subjects showing EEG changes than in those showing none. All the reported differences are statistically significant (p less than 0.01). The probability of hyperpnea modifying the EEG profile becomes progressively less with age, and may be related to the reduced production of CO2 in older subjects. Epileptic subjects (primary generalized epilepsy) produce more CO2 than normal subjects during the hyperpnea test. The statistical data reported in the study show the importance of the size of the drop in ventilatory CO2 in the determination of EEG changes. The rest of hyperpnea in EEG can therefore be validly interpreted only if capnographic variations are measured. A standard quantitative hyperpnea test of this type should be devised, with specification of the hypocapnia level to be achieved.", "contents": "[Quantitative hyperpnea in EEG (author's transl)]. After summarizing the phenomena of respiratory physiology involved in the hyperpnea test, the author studies the quantitative relation between the drop in PECO2 (pressure of CO2 in expired air) and changes in the EEG during hyperpnea. Normal subjects are divided into two groups of a hundred (6 to 19 1/2 years of age; 20 to 59 1/2 years of age). The PECO2 at rest is higher among the young subjects than among the adults, and its decline during hyperpnea is sharper. Thus, children show discrete respiratory acidosis in comparison with adults. The EEG of normal adults is practically unchanged during hyperpnea whereas, in the young group, moderate changes in the profile were observed in 45 out of 100 cases (classified empirically as normal). The PECO2 reaches a lower level in subjects showing EEG changes than in those showing none. All the reported differences are statistically significant (p less than 0.01). The probability of hyperpnea modifying the EEG profile becomes progressively less with age, and may be related to the reduced production of CO2 in older subjects. Epileptic subjects (primary generalized epilepsy) produce more CO2 than normal subjects during the hyperpnea test. The statistical data reported in the study show the importance of the size of the drop in ventilatory CO2 in the determination of EEG changes. The rest of hyperpnea in EEG can therefore be validly interpreted only if capnographic variations are measured. A standard quantitative hyperpnea test of this type should be devised, with specification of the hypocapnia level to be achieved."}
{"id": "PMID:26166", "title": "Comparison of beta-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle.", "content": "Blood flow changes in response to various drugs in simulataneously autoperfused canine subcutaneous adipose tissue and gracilis muscle were compared to study the vascular beta-adrenoceptors. Compared to isoprenaline the beta 2-selective agonist salbutamol was 4--6 times more potent as a vasodilator in the muscle than in adipose tissue. Furthermore two beta 1-selective agonists (Tazolol and H80/62) caused vasodilatation in adipose tissue but not in the gracilis muscle. When given by close i.a. injection after beta-adrenoceptor blockade, adrenaline was a more potent vasoconstrictor than noradrenaline in both tissues. Before beta-blockade, however, noradrenaline was the more potent vasoconstrictor in the gracilis muscle whereas adrenaline was more potent in adipose tissue. Intravenous infusion of adrenaline in doses causing vasodilatation in the muscle caused vasoconstriction in adipose tissue whereas intravenous infusion of noradrenaline caused vasoconstriction in both tissues. The present findings suggest that the beta-adrenoceptors mediating vasodilatation in skeletal muscle are mainly ose tissue. Since adrenaline is a much more potent beta2- than beta1-agonist, these differences point to different roles of intravascular adrenaline in the two sites. In skeletal muscle circulating adrenaline is mainly a vasodilator whereas in subcutaneous adipose tissue it mainly acts as a vasoconstrictor.", "contents": "Comparison of beta-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle. Blood flow changes in response to various drugs in simulataneously autoperfused canine subcutaneous adipose tissue and gracilis muscle were compared to study the vascular beta-adrenoceptors. Compared to isoprenaline the beta 2-selective agonist salbutamol was 4--6 times more potent as a vasodilator in the muscle than in adipose tissue. Furthermore two beta 1-selective agonists (Tazolol and H80/62) caused vasodilatation in adipose tissue but not in the gracilis muscle. When given by close i.a. injection after beta-adrenoceptor blockade, adrenaline was a more potent vasoconstrictor than noradrenaline in both tissues. Before beta-blockade, however, noradrenaline was the more potent vasoconstrictor in the gracilis muscle whereas adrenaline was more potent in adipose tissue. Intravenous infusion of adrenaline in doses causing vasodilatation in the muscle caused vasoconstriction in adipose tissue whereas intravenous infusion of noradrenaline caused vasoconstriction in both tissues. The present findings suggest that the beta-adrenoceptors mediating vasodilatation in skeletal muscle are mainly ose tissue. Since adrenaline is a much more potent beta2- than beta1-agonist, these differences point to different roles of intravascular adrenaline in the two sites. In skeletal muscle circulating adrenaline is mainly a vasodilator whereas in subcutaneous adipose tissue it mainly acts as a vasoconstrictor."}
{"id": "PMID:26168", "title": "Proton translocating ATPase: its pump, gate, and channel.", "content": "Proton translocating ATPase of oxidative phosphorylation was divided into three functional units: pump, channel, and gate. This was achieved by the use of highly stable pure ATPase obtained from a thermophilic bacterium PS3. The pump and gate were found in a catalytic moiety of the ATPase called TF1, and the channel was in the remaining hydrophobic moiety of the ATPase called TF0 which rendered TF1 sensitive to energy transfer inhibitor such as DCCD. TF1 was composed of five subunits (alpha, 56,000; beta, 53,000; gamma, 32,000; delta, 15,500; epsilon, 11,000 daltons). The essential component of the pump was beta-subunit, since beta gamma-complex or alpha beta delta-complex showed ATPase activity. The gate which blocked passive leakage of protons through TF0 in the proteoliposomes was shown to be gamma delta epsilon-complex in TF1. Both delta- and epsilon-subunits were required to connect alpha beta gamma-complex to TF0. TF0 was identical to the channel and was composed of three kinds of subunits (19,000, 13,500, and 5,400 daltons) and the smallest one was [14C]-DCCD binding protein. When the ATPase was incorporated into vesicles containing highly stable saturated branched phospholipids, ATP-driven electrochemical potential of proton (delta mu H+ = 253mV) and proton gradient driven net synthesis of ATP were demonstrated. For these activities, pump, channel, and gate of proton translocating ATPase were all required.", "contents": "Proton translocating ATPase: its pump, gate, and channel. Proton translocating ATPase of oxidative phosphorylation was divided into three functional units: pump, channel, and gate. This was achieved by the use of highly stable pure ATPase obtained from a thermophilic bacterium PS3. The pump and gate were found in a catalytic moiety of the ATPase called TF1, and the channel was in the remaining hydrophobic moiety of the ATPase called TF0 which rendered TF1 sensitive to energy transfer inhibitor such as DCCD. TF1 was composed of five subunits (alpha, 56,000; beta, 53,000; gamma, 32,000; delta, 15,500; epsilon, 11,000 daltons). The essential component of the pump was beta-subunit, since beta gamma-complex or alpha beta delta-complex showed ATPase activity. The gate which blocked passive leakage of protons through TF0 in the proteoliposomes was shown to be gamma delta epsilon-complex in TF1. Both delta- and epsilon-subunits were required to connect alpha beta gamma-complex to TF0. TF0 was identical to the channel and was composed of three kinds of subunits (19,000, 13,500, and 5,400 daltons) and the smallest one was [14C]-DCCD binding protein. When the ATPase was incorporated into vesicles containing highly stable saturated branched phospholipids, ATP-driven electrochemical potential of proton (delta mu H+ = 253mV) and proton gradient driven net synthesis of ATP were demonstrated. For these activities, pump, channel, and gate of proton translocating ATPase were all required."}
{"id": "PMID:26165", "title": "Role of serotonin in the regulation of respiratory system function.", "content": "Role of serotonin in the regulation of respiratory system function. Acta Physiol. Pol., 1978, 29 (2): 131--138. This study examined respiratory centre reflector excitability, the electrical activity of respiratory muscles, outer breathing, pH and arterial blood gas composition under conditions of experimentally induced serotonin excess or deficiency in 48 dogs. It was found that excess of serotonin in the animals leads a strenghthening of respiratory action in terms of increased respiratory centre bioelectrical excitability, muscular electrical activity and outer respiratory indices, such as frequence, volume and lung ventilation per min. In addition the pH of blood shifted to alkalic and oxygen tension of the blood increased while CO2 tension of the blood decreased.", "contents": "Role of serotonin in the regulation of respiratory system function. Role of serotonin in the regulation of respiratory system function. Acta Physiol. Pol., 1978, 29 (2): 131--138. This study examined respiratory centre reflector excitability, the electrical activity of respiratory muscles, outer breathing, pH and arterial blood gas composition under conditions of experimentally induced serotonin excess or deficiency in 48 dogs. It was found that excess of serotonin in the animals leads a strenghthening of respiratory action in terms of increased respiratory centre bioelectrical excitability, muscular electrical activity and outer respiratory indices, such as frequence, volume and lung ventilation per min. In addition the pH of blood shifted to alkalic and oxygen tension of the blood increased while CO2 tension of the blood decreased."}
{"id": "PMID:26174", "title": "Increased hemoglobin-oxygen affinity in patients with pancreatitis associated with type I and V hyperlipoproteinemia.", "content": "Oxyhemoglobin dissociation curves were performed from blood of subjects with pancreatitis associated with Type V and Type I hyperlipoproteinemia. The hemoglobin-oxygen affininty was markedly increased with P50 varying from 22.3 to 17.7 mmHg. As the hyperlipoproteinemia subsided the clinical and laboratory signs of pancreatic affection disappeared. The increased hemoglobin-oxygen affinity and decreased flow of red cells due to hyperchylomicronemia in the microcirculation may lead to tissue hypoxia, which may act as a precipitating injurious factor leading to pancreatitis during severe hyperlipemia.", "contents": "Increased hemoglobin-oxygen affinity in patients with pancreatitis associated with type I and V hyperlipoproteinemia. Oxyhemoglobin dissociation curves were performed from blood of subjects with pancreatitis associated with Type V and Type I hyperlipoproteinemia. The hemoglobin-oxygen affininty was markedly increased with P50 varying from 22.3 to 17.7 mmHg. As the hyperlipoproteinemia subsided the clinical and laboratory signs of pancreatic affection disappeared. The increased hemoglobin-oxygen affinity and decreased flow of red cells due to hyperchylomicronemia in the microcirculation may lead to tissue hypoxia, which may act as a precipitating injurious factor leading to pancreatitis during severe hyperlipemia."}
{"id": "PMID:26182", "title": "Disturbances of extracellular pK, pNa and pH during no-flow anoxia.", "content": "The initial period of no-flow anoxia can be divided in at least two parts. During the first period lasting approximately 1 min., the O2 available in tissue gives rise to CO2 which increases hydrogen ion activity and may lead to Na+ influx2 (presumably due to increased  membrane permeability to Na+). In the second period, starting after the first minute, the increase in lactate content leads to further decrease in pH and is accompanied by extensive sodium influx and a distinct potassium efflux. However, it is striking that the isolated perfused rat liver is able to tolerate 1 hour of norm-flow anoxia without severe cellular damage, whereas two minutes of no-flow anoxia lead to a decrease in cellular ATP content by 28%.", "contents": "Disturbances of extracellular pK, pNa and pH during no-flow anoxia. The initial period of no-flow anoxia can be divided in at least two parts. During the first period lasting approximately 1 min., the O2 available in tissue gives rise to CO2 which increases hydrogen ion activity and may lead to Na+ influx2 (presumably due to increased  membrane permeability to Na+). In the second period, starting after the first minute, the increase in lactate content leads to further decrease in pH and is accompanied by extensive sodium influx and a distinct potassium efflux. However, it is striking that the isolated perfused rat liver is able to tolerate 1 hour of norm-flow anoxia without severe cellular damage, whereas two minutes of no-flow anoxia lead to a decrease in cellular ATP content by 28%."}
{"id": "PMID:26185", "title": "Skeletal muscle PO2: indicator of peripheral tissue perfusion in haemorrhagic shock.", "content": "The following conclusions can be made on the basis of this work: 1) Measurements of skeletal muscle oxygen tension provide an excellent index of tissue perfusion in haemorrhagic shock. 2) Correction of cardiac output and arterial blood oxygen tension in haemorrhagic shock does not necessarily ensure normal tissue oxygenation. 3) In haemorrhagic shock adequate replacement of blood loss using a balanced salt solution in addition to blood replacement is an integral part of the fluid management. 4) Correction of hypovolemia with an equivalent volume of a plasma expander and subsequent reinfusion of shed blood also returns tissue perfusion to normal. However, this treatment results in marked haemodilution and correction of extracellular fluid loss remains inadequate.", "contents": "Skeletal muscle PO2: indicator of peripheral tissue perfusion in haemorrhagic shock. The following conclusions can be made on the basis of this work: 1) Measurements of skeletal muscle oxygen tension provide an excellent index of tissue perfusion in haemorrhagic shock. 2) Correction of cardiac output and arterial blood oxygen tension in haemorrhagic shock does not necessarily ensure normal tissue oxygenation. 3) In haemorrhagic shock adequate replacement of blood loss using a balanced salt solution in addition to blood replacement is an integral part of the fluid management. 4) Correction of hypovolemia with an equivalent volume of a plasma expander and subsequent reinfusion of shed blood also returns tissue perfusion to normal. However, this treatment results in marked haemodilution and correction of extracellular fluid loss remains inadequate."}
{"id": "PMID:26195", "title": "Pyrimidine nucleotide synthesis in rat embryo cells infected with X14 or H-1 parvovirus.", "content": "The activity of some enzymes involved in pyrimidine nucleotide synthesis was studied in rat embryo cell (REC) cultures infected with X14 or H-1 parvovirus. dCMP aminohydrolase activity of the infected cells was 64--121% greater than that of the mock-infected cells. dTMP synthetase activity was 18% greater in X14 virus-infected cells and 34% lower in H-1 virus-infected cells. These results suggest some differences in the infected cells, as regards the biosynthesis of dTMP. Orotate phosphoribosyltransferase and orotidylate decarboxylase activities appeared nearly unmodified compared to the mock-infected cells. The addition of phosphoribosylpyrophosphate (PRPP) to the cell suspension incubated with [6-14C] orotate increased the specific radioactivity of acid-soluble uracil, 5-fold in the mock-infected cells and 15- --24-fold in the X14 or H-1 virus-infected cells (72 hr p.i.). This result suggests that the lowered pyrimidine nucleotide synthesis in infected cells depends to a large extent on the diminished PRPP pool.", "contents": "Pyrimidine nucleotide synthesis in rat embryo cells infected with X14 or H-1 parvovirus. The activity of some enzymes involved in pyrimidine nucleotide synthesis was studied in rat embryo cell (REC) cultures infected with X14 or H-1 parvovirus. dCMP aminohydrolase activity of the infected cells was 64--121% greater than that of the mock-infected cells. dTMP synthetase activity was 18% greater in X14 virus-infected cells and 34% lower in H-1 virus-infected cells. These results suggest some differences in the infected cells, as regards the biosynthesis of dTMP. Orotate phosphoribosyltransferase and orotidylate decarboxylase activities appeared nearly unmodified compared to the mock-infected cells. The addition of phosphoribosylpyrophosphate (PRPP) to the cell suspension incubated with [6-14C] orotate increased the specific radioactivity of acid-soluble uracil, 5-fold in the mock-infected cells and 15- --24-fold in the X14 or H-1 virus-infected cells (72 hr p.i.). This result suggests that the lowered pyrimidine nucleotide synthesis in infected cells depends to a large extent on the diminished PRPP pool."}
{"id": "PMID:26196", "title": "Increased susceptibility to infection with herpes simplex virus types 1 and 2 of cold-adapted L cells.", "content": "L cells (L-As subline) have been adapted to a temperature of 4 degrees C. In the cold-adapted cells, designated LC3, greater amounts of infectious herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) were synthesized than in the original L-As cells or in another control L-cell line. Two strains of HSV-1 reached higher infectious titres in LC3 cells grown at 36 degrees C than in those grown at 32 degrees C. The HSV-2 strain tested replicated in LC-3 cells grown at 32 degrees C better than at higher temperature. Increased reproduction of HSV in LC3 cells was not due to enhanced adsorption of virions on the cells as compared with control L cells. The multiplication of cold-adapted LC3 cells was and was not more intensive than of L-As and control L cells, respectively. The virological results are confronted with known physiological properties of cold-adapted cells.", "contents": "Increased susceptibility to infection with herpes simplex virus types 1 and 2 of cold-adapted L cells. L cells (L-As subline) have been adapted to a temperature of 4 degrees C. In the cold-adapted cells, designated LC3, greater amounts of infectious herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) were synthesized than in the original L-As cells or in another control L-cell line. Two strains of HSV-1 reached higher infectious titres in LC3 cells grown at 36 degrees C than in those grown at 32 degrees C. The HSV-2 strain tested replicated in LC-3 cells grown at 32 degrees C better than at higher temperature. Increased reproduction of HSV in LC3 cells was not due to enhanced adsorption of virions on the cells as compared with control L cells. The multiplication of cold-adapted LC3 cells was and was not more intensive than of L-As and control L cells, respectively. The virological results are confronted with known physiological properties of cold-adapted cells."}
{"id": "PMID:26197", "title": "CV-1 monkey kidney cell line -- a highly susceptible substrate for diagnosis and study of arboviruses.", "content": "The CV-1 cell line, derived from Cercopithecus aethiops monkey kidneys, acquired in the course of serial passaging an epitheloid morphology and heteroploid karyotype. As compared with Vero and GMK cell lines, the CV-1 line proved to be more susceptible to a broad spectrum of arboviruses belonging to the families Togaviridae and Bunyaviridae. Most of them reached high titres and were markedly cytopathic in CV-1 cells so that all tests based on the cytopathic effect could be carried out. The CV-1 cell line can thus be recommended as an extra-ordinarily suitable substrate for the diagnosis and study of arboviruses.", "contents": "CV-1 monkey kidney cell line -- a highly susceptible substrate for diagnosis and study of arboviruses. The CV-1 cell line, derived from Cercopithecus aethiops monkey kidneys, acquired in the course of serial passaging an epitheloid morphology and heteroploid karyotype. As compared with Vero and GMK cell lines, the CV-1 line proved to be more susceptible to a broad spectrum of arboviruses belonging to the families Togaviridae and Bunyaviridae. Most of them reached high titres and were markedly cytopathic in CV-1 cells so that all tests based on the cytopathic effect could be carried out. The CV-1 cell line can thus be recommended as an extra-ordinarily suitable substrate for the diagnosis and study of arboviruses."}
{"id": "PMID:26198", "title": "Long-term persistence of cell-mediated and humoral immune response in specifically resistant mice given live attenuated langat (E5 \"14\") virus.", "content": "In a long-term experiment, the features of humoral and cell-mediated immunity (CMI) were investigated in mice given intravenously (i.v.) a single dose of live attenuated Langat (E5 \"14\") virus of the tick-borne encephalitis (TBE) complex. The inapparent infection induced in mice specific resistance against challenge with virulent TBE virus, CMI was assayed by the capillary method of murine splenic lymphocyte migrarion inhibition (LMI) in the presence of partially purified TBE vurus. Significant LMI values were observed as early as 4 days after inoculation (p.i.), persisting for at least 15 months. Specific virus neutralizing (VN) antibodies were detected in the pooled serum of mice on the 4th day p.i. by a VN test potentiated with monospecific anti-mouse IgG serum. For the whole experimental period, significant antibody levels were found in the immunized mice which also displayed a complete resistance against 1000 s.c. LD50 of the virulent virus. Organ cultures of brain and spleen from these mice did not yield infections virus.", "contents": "Long-term persistence of cell-mediated and humoral immune response in specifically resistant mice given live attenuated langat (E5 \"14\") virus. In a long-term experiment, the features of humoral and cell-mediated immunity (CMI) were investigated in mice given intravenously (i.v.) a single dose of live attenuated Langat (E5 \"14\") virus of the tick-borne encephalitis (TBE) complex. The inapparent infection induced in mice specific resistance against challenge with virulent TBE virus, CMI was assayed by the capillary method of murine splenic lymphocyte migrarion inhibition (LMI) in the presence of partially purified TBE vurus. Significant LMI values were observed as early as 4 days after inoculation (p.i.), persisting for at least 15 months. Specific virus neutralizing (VN) antibodies were detected in the pooled serum of mice on the 4th day p.i. by a VN test potentiated with monospecific anti-mouse IgG serum. For the whole experimental period, significant antibody levels were found in the immunized mice which also displayed a complete resistance against 1000 s.c. LD50 of the virulent virus. Organ cultures of brain and spleen from these mice did not yield infections virus."}
{"id": "PMID:26199", "title": "Attenuated variants of eastern equine encephalomyelitis virus: pathomorphological, immunofluorescence and virological studies of infection in Syrian hamsters.", "content": "A virulent strain of eastern equine encephalomyelitis virus produced in hamsters a lethal infection with severe lesions of nerve cells predominatly in the anterior parts of the brain. Parenchyma necroses occurred in the liver and lymphoid organs. Infectious virus and viral antigen were found in all the organs examined with the greatest accumulation in the brain. Attenuated variants of the virus produced in most hamsters an inapparent infection. In some animals without clinical signs, focal inflammatory-dystrophic lesions were found in the central nervous system (CNS) and the liver, as were immunomorphological changes in the lymphoid tissue. In the latter infectious virus could be detected for 6 days after inoculation (p.i.), whereas in the brain only viral antigen could be found up to 14 days. At 3 and 6 months p.i., no persistence of attenuated virus in the brain and lymphoid tissues could be established by organ culture and co-cultivation methods. Nor was virus antigen detected. No pathomorphological changes or proliferative-hypertrophic astrocyte reaction were found.", "contents": "Attenuated variants of eastern equine encephalomyelitis virus: pathomorphological, immunofluorescence and virological studies of infection in Syrian hamsters. A virulent strain of eastern equine encephalomyelitis virus produced in hamsters a lethal infection with severe lesions of nerve cells predominatly in the anterior parts of the brain. Parenchyma necroses occurred in the liver and lymphoid organs. Infectious virus and viral antigen were found in all the organs examined with the greatest accumulation in the brain. Attenuated variants of the virus produced in most hamsters an inapparent infection. In some animals without clinical signs, focal inflammatory-dystrophic lesions were found in the central nervous system (CNS) and the liver, as were immunomorphological changes in the lymphoid tissue. In the latter infectious virus could be detected for 6 days after inoculation (p.i.), whereas in the brain only viral antigen could be found up to 14 days. At 3 and 6 months p.i., no persistence of attenuated virus in the brain and lymphoid tissues could be established by organ culture and co-cultivation methods. Nor was virus antigen detected. No pathomorphological changes or proliferative-hypertrophic astrocyte reaction were found."}
{"id": "PMID:26200", "title": "Transmissible virus dementia. I. An unusual space and time clustering of Creutzfeldt-Jakob disease and of other organic presenile dementia cases.", "content": "A peculiar grouping of Creutzfeldt-Jacob disease (CJD) and of other organic presenile dementia (OPD) cases in a small, prevalently rural area in Czechoslovakia to the east of 19 degrees 35' E and to the north of 48 degrees 15' N was studied. Between August, 1972 and November, 1976, three histologically proven CJD cases, bearing no sporadic of familial patterns, were observed. The distance between their dwellings was 13--17 km. In addition, seven cases of OPD were detected in the same area, two of them being suspected as possible CJD according to clinical evidence.", "contents": "Transmissible virus dementia. I. An unusual space and time clustering of Creutzfeldt-Jakob disease and of other organic presenile dementia cases. A peculiar grouping of Creutzfeldt-Jacob disease (CJD) and of other organic presenile dementia (OPD) cases in a small, prevalently rural area in Czechoslovakia to the east of 19 degrees 35' E and to the north of 48 degrees 15' N was studied. Between August, 1972 and November, 1976, three histologically proven CJD cases, bearing no sporadic of familial patterns, were observed. The distance between their dwellings was 13--17 km. In addition, seven cases of OPD were detected in the same area, two of them being suspected as possible CJD according to clinical evidence."}
{"id": "PMID:26201", "title": "Transmissible virus dementia. II. Neurohistology of three, geographically clustered cases of Creutzfeldt-Jakob disease.", "content": "Histopathological findings in three temporo-spatially linked cases of Creutzfeldt-Jakob disease (CJD) are reported. The patients were males, unrelated and without positive family history. Their mean age at the onset of the disease was 52.3 years. The mean duration of the illness was 6.6 months; the clinical symptomatology differed considerably. Neurohistology revealed in all patients a neuronal loss, intracyoplasmic vacuolation, spongiosis and astrocytosis. Besides the cortical regions, basal ganglia and cerebella were severely affected. All cases were pathologically suggestive of the cortico-striato-cerebella variant of CJD. Attention is drawn to this apparent topical similarity of most pronounced lesions. The possible significance of the pathoanatomical consistency, observed in the cases studied, for the unusual pattern of natural occurrence of CJD is considered.", "contents": "Transmissible virus dementia. II. Neurohistology of three, geographically clustered cases of Creutzfeldt-Jakob disease. Histopathological findings in three temporo-spatially linked cases of Creutzfeldt-Jakob disease (CJD) are reported. The patients were males, unrelated and without positive family history. Their mean age at the onset of the disease was 52.3 years. The mean duration of the illness was 6.6 months; the clinical symptomatology differed considerably. Neurohistology revealed in all patients a neuronal loss, intracyoplasmic vacuolation, spongiosis and astrocytosis. Besides the cortical regions, basal ganglia and cerebella were severely affected. All cases were pathologically suggestive of the cortico-striato-cerebella variant of CJD. Attention is drawn to this apparent topical similarity of most pronounced lesions. The possible significance of the pathoanatomical consistency, observed in the cases studied, for the unusual pattern of natural occurrence of CJD is considered."}
{"id": "PMID:26202", "title": "Comparative studies on sindbis virus strains isolated in Slovakia.", "content": "Two variants of Sindbis virus strains were distinguished according to the dextran sulphate (DS) marker. Large-plague strains freshly isolated from Cricetus cricetus and Rana ridibunda produced exclusively small plaques after DS treatment. The prototype Sindbis virus strain produced both large and small plaques after DS treatment. Kinetic haemagglutination-inhibition tests revealed a higher reactivity of freshly isolated strains than of the prototype strain. For differentiation of newly isolated strains of Sindbis virus, their sensitivity to sodium deoxycholate is recommended: a freshly isolated strain proved to be resistant to sodium deoxycholate.", "contents": "Comparative studies on sindbis virus strains isolated in Slovakia. Two variants of Sindbis virus strains were distinguished according to the dextran sulphate (DS) marker. Large-plague strains freshly isolated from Cricetus cricetus and Rana ridibunda produced exclusively small plaques after DS treatment. The prototype Sindbis virus strain produced both large and small plaques after DS treatment. Kinetic haemagglutination-inhibition tests revealed a higher reactivity of freshly isolated strains than of the prototype strain. For differentiation of newly isolated strains of Sindbis virus, their sensitivity to sodium deoxycholate is recommended: a freshly isolated strain proved to be resistant to sodium deoxycholate."}
{"id": "PMID:26203", "title": "T lymphocytes as an indicator in influenza vaccination, influenza and acute respiratory diseases.", "content": "Significant differences in T-lymphocyte counts in the peripheral blood of normal subject and volunteers vaccinated with live and inactivated influenza vaccines as well as patients with influenza and viral acute respiratory diseases (ARD) were demonstrated. A laboratory test using T lymphocytes was proposed for the evaluation of the safety of live influenza vaccine.", "contents": "T lymphocytes as an indicator in influenza vaccination, influenza and acute respiratory diseases. Significant differences in T-lymphocyte counts in the peripheral blood of normal subject and volunteers vaccinated with live and inactivated influenza vaccines as well as patients with influenza and viral acute respiratory diseases (ARD) were demonstrated. A laboratory test using T lymphocytes was proposed for the evaluation of the safety of live influenza vaccine."}
{"id": "PMID:26208", "title": "Temperature-sensitive mutants of vaccinia virus. I. Isolation and preliminary characterization.", "content": "Fifty-seven temperature-sensitive (ts) mutants of a neurotropic variant of vaccinia virus were obtained. A comparison of the effectiveness of 6 different mutagens showed that in in vivo experiments nitrosomethylurea induced 10%, nitrosoguanidine 8%, and bromodeoxyuridine 2.5% ts mutants. In vitro, at the same degree of inactivation, UV irradiation, hydroxylamine and nitrous acid induced 2.5% ts mutants. Out of 49 mutants studied, 27 had a DNA+ phenotype, 19 a DNA+/-and 3 a DNA- phenotype. Under permissive conditions, two thirds of all the mutants tested formed thermolabile virions. In experiments on genetic recombination, the recombination frequency between different pairs was from 2.8 to 57%. Seven of the mutants were plotted on the virus genetic map in a certain sequence.", "contents": "Temperature-sensitive mutants of vaccinia virus. I. Isolation and preliminary characterization. Fifty-seven temperature-sensitive (ts) mutants of a neurotropic variant of vaccinia virus were obtained. A comparison of the effectiveness of 6 different mutagens showed that in in vivo experiments nitrosomethylurea induced 10%, nitrosoguanidine 8%, and bromodeoxyuridine 2.5% ts mutants. In vitro, at the same degree of inactivation, UV irradiation, hydroxylamine and nitrous acid induced 2.5% ts mutants. Out of 49 mutants studied, 27 had a DNA+ phenotype, 19 a DNA+/-and 3 a DNA- phenotype. Under permissive conditions, two thirds of all the mutants tested formed thermolabile virions. In experiments on genetic recombination, the recombination frequency between different pairs was from 2.8 to 57%. Seven of the mutants were plotted on the virus genetic map in a certain sequence."}
{"id": "PMID:26209", "title": "Pseudotype particles of vesicular stomatitis virus with surface antigens of bovine leukaemia virus--VSV (BLV) -- as a sensitive probe for detecting antibodies in the sera of spontaneously infected cattle.", "content": "Phenotypically mixed particles containing the genome of vesicular stomatitis virus (VSV) and envelope antigen corresponding to bovine leukaemia virus (BLV) -- the VSV (BLV) pseudotypes -- can be employed as a rapid, specific and sensitive probe for detecting BLV-neutralizing antibodies in bovine sera.", "contents": "Pseudotype particles of vesicular stomatitis virus with surface antigens of bovine leukaemia virus--VSV (BLV) -- as a sensitive probe for detecting antibodies in the sera of spontaneously infected cattle. Phenotypically mixed particles containing the genome of vesicular stomatitis virus (VSV) and envelope antigen corresponding to bovine leukaemia virus (BLV) -- the VSV (BLV) pseudotypes -- can be employed as a rapid, specific and sensitive probe for detecting BLV-neutralizing antibodies in bovine sera."}
{"id": "PMID:26210", "title": "Comparative study of virion transcriptase of some influenza virus strains.", "content": "The activities, the temperature and pH optima of in vitro functioning and stability upon heating of virion transcriptase of 10 human influenza virus A strains differing in reactogenicity and isolated in different epidemiological situations, and of fowl plague virus (FVP) were compared. As compared with virion transcriptase of human influenza virus strains studied, that of FPV had a higher pH optimum, was capable of functioning in vitro at a higher temperature and was more stable on heating. Freshly isolated and vaccine influenza virus strains on the one hand and strains isolated at the peak and in the end of an epidemic did not differ in the virion transcriptase properties. The virion transcriptase of a strain isolated from a local influenza outbreak was much less active than transcriptase of a highly epiedmic strain.", "contents": "Comparative study of virion transcriptase of some influenza virus strains. The activities, the temperature and pH optima of in vitro functioning and stability upon heating of virion transcriptase of 10 human influenza virus A strains differing in reactogenicity and isolated in different epidemiological situations, and of fowl plague virus (FVP) were compared. As compared with virion transcriptase of human influenza virus strains studied, that of FPV had a higher pH optimum, was capable of functioning in vitro at a higher temperature and was more stable on heating. Freshly isolated and vaccine influenza virus strains on the one hand and strains isolated at the peak and in the end of an epidemic did not differ in the virion transcriptase properties. The virion transcriptase of a strain isolated from a local influenza outbreak was much less active than transcriptase of a highly epiedmic strain."}
{"id": "PMID:26212", "title": "The benzodiazepines.", "content": "The benzodiazepines are remarkably effective anxiolytic drugs. However, they are prone to misuse by both physicians and patients. They should be used in clearly defined clinical situations for short periods, at the lowest possible dosages. Although rare, toxicity can be severe. These agents should be used with caution in persons likely to abuse medication, in the elderly, in patients with glaucoma and in patiens with known hepatic impairment. Sudden cessation may be followed by a withdrawal state.", "contents": "The benzodiazepines. The benzodiazepines are remarkably effective anxiolytic drugs. However, they are prone to misuse by both physicians and patients. They should be used in clearly defined clinical situations for short periods, at the lowest possible dosages. Although rare, toxicity can be severe. These agents should be used with caution in persons likely to abuse medication, in the elderly, in patients with glaucoma and in patiens with known hepatic impairment. Sudden cessation may be followed by a withdrawal state."}
{"id": "PMID:26213", "title": "Non-specific aorto-arteritis in Singapore with special reference to hypertension.", "content": "Aorto-arteritis has recently emerged as a distinct disease entity with involvement of aorta and its major branches by a non-specific inflammation of unknown etiology. Though the distribution of this disease is worldwide, it is more prevalent in Japan, India, and South-east Asia. This paper describes a series of 48 cases seen in Singapore and emphasizes the protean nature of this disease. Though modes of clinical presentation were many, hypertension appeared to be the commonest as it occurred in 33 patients, giving an incidence of 69 per cent. This incidence was much higher than the 48 per cent reported among Europeans and 42 per cent reported among South Africans. It would therefore appear that hypertension was a far more common manifestation of aorto-arteritis among Asians. The commonest cause of hypertension in aorto-arteritis in this series was renovascular, with renal artery stenosis or occlusion occurring in 27 cases (85 per cent). The frequency of involvement of the renal artery is much greater than the 34 per cent reported by the Japanese. Therefore renovascular hypertension should be regarded as a predominant feature of aorto-arteritis in Singapore.", "contents": "Non-specific aorto-arteritis in Singapore with special reference to hypertension. Aorto-arteritis has recently emerged as a distinct disease entity with involvement of aorta and its major branches by a non-specific inflammation of unknown etiology. Though the distribution of this disease is worldwide, it is more prevalent in Japan, India, and South-east Asia. This paper describes a series of 48 cases seen in Singapore and emphasizes the protean nature of this disease. Though modes of clinical presentation were many, hypertension appeared to be the commonest as it occurred in 33 patients, giving an incidence of 69 per cent. This incidence was much higher than the 48 per cent reported among Europeans and 42 per cent reported among South Africans. It would therefore appear that hypertension was a far more common manifestation of aorto-arteritis among Asians. The commonest cause of hypertension in aorto-arteritis in this series was renovascular, with renal artery stenosis or occlusion occurring in 27 cases (85 per cent). The frequency of involvement of the renal artery is much greater than the 34 per cent reported by the Japanese. Therefore renovascular hypertension should be regarded as a predominant feature of aorto-arteritis in Singapore."}
{"id": "PMID:26214", "title": "Involvement of the cardiac conducting system in panarteritis nodosa.", "content": "Histopathological observations on the conduction system of the heart were carried out in three cases of panarteritis nodosa. This specialized tissue was involved in each case secondary to ischemia and/or periarterial extension of the inflammatory process affecting the nutrient arteries of the conducting system. The high risk of disturbances in impulse formation and conduction in patients with panarteritis is emphasized as well as the need for appropriate clinical investigation (protracted cardiac monitoring and control by catheter recording and stimulation) in order to secure early detection and prevention of life-threatening arrhythmias.", "contents": "Involvement of the cardiac conducting system in panarteritis nodosa. Histopathological observations on the conduction system of the heart were carried out in three cases of panarteritis nodosa. This specialized tissue was involved in each case secondary to ischemia and/or periarterial extension of the inflammatory process affecting the nutrient arteries of the conducting system. The high risk of disturbances in impulse formation and conduction in patients with panarteritis is emphasized as well as the need for appropriate clinical investigation (protracted cardiac monitoring and control by catheter recording and stimulation) in order to secure early detection and prevention of life-threatening arrhythmias."}
{"id": "PMID:26219", "title": "Drug therapy in the treatment of minimal brain dysfunction.", "content": "The pharmacotherapy of minimal brain dysfunction (MBD) is reviewed. Studies using central nervous system (CNS) stimulants (amphetamines and methylphenidate, deanol, pemoline, caffeine), antidepressants (imipramine and desipramine), anticonvulsants (phenytoin and primidone), antianxiety agents (chlordiazepoxide, hydroxyzine, meprobamate), antipsychotic agents (phenothiazines, thioxanthenes, butyrophenones) and miscellaneous agents (benztropine, thyrotropin-releasing hormone, megavitamins) are discussed. When drugs are indicated, the CNS stimulants are the agents of choice in the treatment of MBD. The use of tricyclic antidepressants in MBD is regarded as investigational and warrants careful monitoring to minimize toxicities. Anticonvulsants have been ineffective in controlling behavior problems; however, phenytoin may be helpful in auditory perception problems. Anti-anxiety and antipsychotic agents are not as desirable as the CNS stimulants for treatment since they do not decrease distractibility or increase attention spans.", "contents": "Drug therapy in the treatment of minimal brain dysfunction. The pharmacotherapy of minimal brain dysfunction (MBD) is reviewed. Studies using central nervous system (CNS) stimulants (amphetamines and methylphenidate, deanol, pemoline, caffeine), antidepressants (imipramine and desipramine), anticonvulsants (phenytoin and primidone), antianxiety agents (chlordiazepoxide, hydroxyzine, meprobamate), antipsychotic agents (phenothiazines, thioxanthenes, butyrophenones) and miscellaneous agents (benztropine, thyrotropin-releasing hormone, megavitamins) are discussed. When drugs are indicated, the CNS stimulants are the agents of choice in the treatment of MBD. The use of tricyclic antidepressants in MBD is regarded as investigational and warrants careful monitoring to minimize toxicities. Anticonvulsants have been ineffective in controlling behavior problems; however, phenytoin may be helpful in auditory perception problems. Anti-anxiety and antipsychotic agents are not as desirable as the CNS stimulants for treatment since they do not decrease distractibility or increase attention spans."}
{"id": "PMID:26220", "title": "Acidosis of synovial fluid correlates with synovial fluid leukocytosis.", "content": "The antibacterial activity of aminoglycoside antibiotics is significantly reduced by lowering the pH of the incubation medium. Since gram-negative septic arthritis responds poorly to aminoglycoside antibiotic therapy, we sought to determine whether synovial fluid acidosis contributes to this poor outcome. Synovial fluid samples from 22 patients with various forms of acute and chronic arthritis were examined for white blood cell count and pH. A close correlation (r = -0.92, p is less than 0.001) between an increasing white blood cell count and a decreasing pH was demonstrated. Since septic arthritis is associated with high white blood cell counts, in synovial fluid, the resultant low pH may contribute to the poor response to gram-negative septic arthritis treated with aminoglycoside antibiotics.", "contents": "Acidosis of synovial fluid correlates with synovial fluid leukocytosis. The antibacterial activity of aminoglycoside antibiotics is significantly reduced by lowering the pH of the incubation medium. Since gram-negative septic arthritis responds poorly to aminoglycoside antibiotic therapy, we sought to determine whether synovial fluid acidosis contributes to this poor outcome. Synovial fluid samples from 22 patients with various forms of acute and chronic arthritis were examined for white blood cell count and pH. A close correlation (r = -0.92, p is less than 0.001) between an increasing white blood cell count and a decreasing pH was demonstrated. Since septic arthritis is associated with high white blood cell counts, in synovial fluid, the resultant low pH may contribute to the poor response to gram-negative septic arthritis treated with aminoglycoside antibiotics."}
{"id": "PMID:26221", "title": "Chronic cutaneous graft-versus-host disease in man.", "content": "This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.", "contents": "Chronic cutaneous graft-versus-host disease in man. This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed."}
{"id": "PMID:26222", "title": "Hypnosis and related clinical behavior.", "content": "The essential aspect in the experience of the hypnotized person is the altered or distorted perception that is suggested to him. Not all people are capable of the experience, but it is possible that spontaneous distortions occur in those with high hypnotizability. These distortions are frequently experienced as frightening symptoms. The author draws attention to the similarity between hysterical symptoms and events in hypnosis and to the high hypnotic responsivity in hysterical subjects reported in the clinical literature of the nineteenth century. Phobic patients have relatively high hypnotic responsivity. The author believes that it is sometimes possible to predict hypnotizability from clinical behavior, and that hypnotic responsivity can be utilized in psychodynamically sensitive therapy to teach such patients that they can learn to gain control of their symptoms.", "contents": "Hypnosis and related clinical behavior. The essential aspect in the experience of the hypnotized person is the altered or distorted perception that is suggested to him. Not all people are capable of the experience, but it is possible that spontaneous distortions occur in those with high hypnotizability. These distortions are frequently experienced as frightening symptoms. The author draws attention to the similarity between hysterical symptoms and events in hypnosis and to the high hypnotic responsivity in hysterical subjects reported in the clinical literature of the nineteenth century. Phobic patients have relatively high hypnotic responsivity. The author believes that it is sometimes possible to predict hypnotizability from clinical behavior, and that hypnotic responsivity can be utilized in psychodynamically sensitive therapy to teach such patients that they can learn to gain control of their symptoms."}
{"id": "PMID:26223", "title": "Drug use by the polysurgical patient.", "content": "The authors compared the drug use of 23 patients with 5 or more major surgeries (mean number of surgeries = 9.8) with that of a matched control group (mean number of surgeries = 1). Total drug use of the polysurgical patients was 3.7 times greater than that of the controls and involved narcotics, analgesics, barbiturates, and minor tranquilizers. The authors describe the characteristics of polysurgical patients, one of which is chronic pain, and propose a treatment plan that involves psychological intervention for the patient and his or her family.", "contents": "Drug use by the polysurgical patient. The authors compared the drug use of 23 patients with 5 or more major surgeries (mean number of surgeries = 9.8) with that of a matched control group (mean number of surgeries = 1). Total drug use of the polysurgical patients was 3.7 times greater than that of the controls and involved narcotics, analgesics, barbiturates, and minor tranquilizers. The authors describe the characteristics of polysurgical patients, one of which is chronic pain, and propose a treatment plan that involves psychological intervention for the patient and his or her family."}
{"id": "PMID:26224", "title": "The treatment of severely depressed schizophrenic patients.", "content": "The diagnosis and treatment of severe masked depression in schizophrenia is discussed, and the difficulties in management are stressed, with particular reference to drug therapy, E.C.T., and psychotherapy.", "contents": "The treatment of severely depressed schizophrenic patients. The diagnosis and treatment of severe masked depression in schizophrenia is discussed, and the difficulties in management are stressed, with particular reference to drug therapy, E.C.T., and psychotherapy."}
{"id": "PMID:26225", "title": "[Investigations on the plasm amino acids of old patients with rheumatoid arthritis (author's transl)].", "content": "The amino acids of blood plasma of 43 patients with rheumatoid arthritis (RA) and 19 controls were investigated by ion exchange chromatography. It was proofed simultaneously whether human more than 60 years old exhibit significantly different amino acid concentrations from younger individuals. It was found that RA patients more than 60 years differ significantly in 23 out of 30 amino acids. Only Asparagine was decreased, all other amino acids were increased. The controls did not show the same uniform direction of results. Older individuals exhibited differences in only 14 amino acids. Phosphoserine, Cystathionine and Arginine were increased to a great extent while Threonine, 1-Methylhistidine and Tryptophane were apparently diminished in this group of age.", "contents": "[Investigations on the plasm amino acids of old patients with rheumatoid arthritis (author's transl)]. The amino acids of blood plasma of 43 patients with rheumatoid arthritis (RA) and 19 controls were investigated by ion exchange chromatography. It was proofed simultaneously whether human more than 60 years old exhibit significantly different amino acid concentrations from younger individuals. It was found that RA patients more than 60 years differ significantly in 23 out of 30 amino acids. Only Asparagine was decreased, all other amino acids were increased. The controls did not show the same uniform direction of results. Older individuals exhibited differences in only 14 amino acids. Phosphoserine, Cystathionine and Arginine were increased to a great extent while Threonine, 1-Methylhistidine and Tryptophane were apparently diminished in this group of age."}
{"id": "PMID:26226", "title": "[DNA--\"rejoining\" in lymphycytes of patients with a minifestation of rheumatoid arthritis in older age (author's transl)].", "content": "Relations between the time of manifestation of the disease and the course of the rheumatoid arthritis were found from the clinic frequently. Patients with later first manifestation of rheumatoid arthritis show clear differences against patients with earlier manifestation of the disease at which the late first manifestation a high activity of the process of the disease exhibit. In males first manifestation of rheumatoid arthritis in middle age of 54,5 years was observed, while in a first manifestation of rheumatoid arthritis in middle age of 47 years a normal course of the disease was found. The difference between the both courses was proved as significantly. In former investigations we could prove that in patients with rheumatoid arthritis the 3H-Thymidin-build in the course of not programmed DNA-synthesis in the DNA of lymphocytes after damage with ionizing was retarded. The rate of not programmed DNA synthesis seems to be in old persons equal. The ligase reaction is possibly diminished because the number of DNA-strand breakes with the age is strong increasing.", "contents": "[DNA--\"rejoining\" in lymphycytes of patients with a minifestation of rheumatoid arthritis in older age (author's transl)]. Relations between the time of manifestation of the disease and the course of the rheumatoid arthritis were found from the clinic frequently. Patients with later first manifestation of rheumatoid arthritis show clear differences against patients with earlier manifestation of the disease at which the late first manifestation a high activity of the process of the disease exhibit. In males first manifestation of rheumatoid arthritis in middle age of 54,5 years was observed, while in a first manifestation of rheumatoid arthritis in middle age of 47 years a normal course of the disease was found. The difference between the both courses was proved as significantly. In former investigations we could prove that in patients with rheumatoid arthritis the 3H-Thymidin-build in the course of not programmed DNA-synthesis in the DNA of lymphocytes after damage with ionizing was retarded. The rate of not programmed DNA synthesis seems to be in old persons equal. The ligase reaction is possibly diminished because the number of DNA-strand breakes with the age is strong increasing."}
{"id": "PMID:26227", "title": "[Unexplained accelerated blood cells sedimentation rate in the aged (author's transl)].", "content": "There is one reason for unexplained accelerated blood cells sedimentation rate in the aged, which is often neglected:Polymyalgia arteriitica or Arteriitis temporalis. Long-term therapy with cortison normalizes pains and sedimentation rate. Nevertheless, short-term treatment is a way to diagnose the disease \"ex juvantibus\".", "contents": "[Unexplained accelerated blood cells sedimentation rate in the aged (author's transl)]. There is one reason for unexplained accelerated blood cells sedimentation rate in the aged, which is often neglected:Polymyalgia arteriitica or Arteriitis temporalis. Long-term therapy with cortison normalizes pains and sedimentation rate. Nevertheless, short-term treatment is a way to diagnose the disease \"ex juvantibus\"."}
{"id": "PMID:26228", "title": "[Interactions of drugs, used in the treatment of rheumatism in the elderly (author's transl)].", "content": "This paper reviews the possibilities of interactions of drugs, used in the treatment of rheumatism in the elderly. Exspecially glycosides, antikoagulants, diuretics, uricosurics, salicylates, barbiturates and corticosteroides are discussed.", "contents": "[Interactions of drugs, used in the treatment of rheumatism in the elderly (author's transl)]. This paper reviews the possibilities of interactions of drugs, used in the treatment of rheumatism in the elderly. Exspecially glycosides, antikoagulants, diuretics, uricosurics, salicylates, barbiturates and corticosteroides are discussed."}
{"id": "PMID:26229", "title": "[Scleroderma, an ageing process? I. Clinical and immunological aspects (author's transl)].", "content": "Scleroderma with its different manifestations is mainly a disease of connective tissue and of vascular system. Next the alteration to collagen, which is demonstrable in lesions by decrease of embryonale collagen type III, there are also humoral and cellular phenomens of autoimmunity. In more than 70% of our patients we found antinuclear antibodies, and in most of them, we found with the leukocytemigration--inhibition-test cellular immunphenomenons to RNA, collagen and muscle. There is a small connection between ageing and immunological defense and repair, accordingly of immunocytes and fibroblasts. Further more precise characterization of this cell-compartments under the aspect of a premature ageing could bring a new understanding in the largely unknown etiopathogenese of scleroderma.", "contents": "[Scleroderma, an ageing process? I. Clinical and immunological aspects (author's transl)]. Scleroderma with its different manifestations is mainly a disease of connective tissue and of vascular system. Next the alteration to collagen, which is demonstrable in lesions by decrease of embryonale collagen type III, there are also humoral and cellular phenomens of autoimmunity. In more than 70% of our patients we found antinuclear antibodies, and in most of them, we found with the leukocytemigration--inhibition-test cellular immunphenomenons to RNA, collagen and muscle. There is a small connection between ageing and immunological defense and repair, accordingly of immunocytes and fibroblasts. Further more precise characterization of this cell-compartments under the aspect of a premature ageing could bring a new understanding in the largely unknown etiopathogenese of scleroderma."}
{"id": "PMID:26230", "title": "[The total alloplasty of the hip in very aged people (author's transl)].", "content": "By means of a short follow-up study about all patients of more than eighty years of age, who had done a total alloplasty of the hip in the BG-Unfallklinik Ludwigshafen/Rhein, this is a report of the problems of surgery in the very aged people, the indication of surgery, the pre- and postoperative management and furthermore on complications and long-time results.", "contents": "[The total alloplasty of the hip in very aged people (author's transl)]. By means of a short follow-up study about all patients of more than eighty years of age, who had done a total alloplasty of the hip in the BG-Unfallklinik Ludwigshafen/Rhein, this is a report of the problems of surgery in the very aged people, the indication of surgery, the pre- and postoperative management and furthermore on complications and long-time results."}
{"id": "PMID:26231", "title": "[Age and time of hospitalization (author's transl)].", "content": "A reduction of the time of hospitalization has been repeatedly considered as a cost-saving possibility in the projects of reforming the hospital system. The time of hospitalization of older patients is longer than that of younger patients. Every plan to reduce it fails for lack of flanking institutions, such as geriatric hospitals, nursing homes, etc. However, all age groups include a small number of patients staying in hospital for long periods of time and taking therfore a disproportionately large share in the nursing day total. This fact is proved by statistic data on 11,875 internal cases admitted to the Nuremberg hospitals. The transformation of the complex acute-case hospital into a graded ward system could create a possibility of accommodating, and attending to, this small group of people in better medical conditions and on better financial terms.", "contents": "[Age and time of hospitalization (author's transl)]. A reduction of the time of hospitalization has been repeatedly considered as a cost-saving possibility in the projects of reforming the hospital system. The time of hospitalization of older patients is longer than that of younger patients. Every plan to reduce it fails for lack of flanking institutions, such as geriatric hospitals, nursing homes, etc. However, all age groups include a small number of patients staying in hospital for long periods of time and taking therfore a disproportionately large share in the nursing day total. This fact is proved by statistic data on 11,875 internal cases admitted to the Nuremberg hospitals. The transformation of the complex acute-case hospital into a graded ward system could create a possibility of accommodating, and attending to, this small group of people in better medical conditions and on better financial terms."}
{"id": "PMID:26232", "title": "[Suicides in patients of a geriatric hospital (author's transl)].", "content": "Problems of suicide during treatment in an internal geriatric hospital are discussed. Particular attention is given to possibilities of preventation.", "contents": "[Suicides in patients of a geriatric hospital (author's transl)]. Problems of suicide during treatment in an internal geriatric hospital are discussed. Particular attention is given to possibilities of preventation."}
{"id": "PMID:26233", "title": "[Cause and incidence of suicides and attempted suicides by patients over 65 years old in psychiatric hospitals (author's transl)].", "content": "Case reports of 184 suicides and attempted suicides in the six hospitals of the Landschaftsverband Rheinland from 1964-1974 were analyzed. 25 patients were over 65 years old. The combination of almost 30 variables revealed no significant constellation caused by old age. Furthermore no criterias could be found to assess increased suicidal tendency of hospitalized patients. Two conclusions are of importance. 1. The risk of suicides in hospitals does not increase by loosening of restrictions and open environment. 2. The concept of hospital suicide should include the time after being discharged and enlarge on other institutions which are involved in the psychiatric care system. A center of crisis intervention is disucssed which offers its services to different institutions for the purpose of suicide prophylaxis.", "contents": "[Cause and incidence of suicides and attempted suicides by patients over 65 years old in psychiatric hospitals (author's transl)]. Case reports of 184 suicides and attempted suicides in the six hospitals of the Landschaftsverband Rheinland from 1964-1974 were analyzed. 25 patients were over 65 years old. The combination of almost 30 variables revealed no significant constellation caused by old age. Furthermore no criterias could be found to assess increased suicidal tendency of hospitalized patients. Two conclusions are of importance. 1. The risk of suicides in hospitals does not increase by loosening of restrictions and open environment. 2. The concept of hospital suicide should include the time after being discharged and enlarge on other institutions which are involved in the psychiatric care system. A center of crisis intervention is disucssed which offers its services to different institutions for the purpose of suicide prophylaxis."}
{"id": "PMID:26234", "title": "[Historical aspects of suicide in the old age (author's transl)].", "content": "Beginning with a very different attitude of the antiquity taken up to suicide, which was normally not regarded as a self-murdering but as a voluntary departing this life and as such as a philosophically based act of liberty especially by members of the stoic system who not seldom commited suicide themselves, another estimation is discussed which was exercised by the Pythagoreans and the members of the Aristotele's doctrine. They rejected suicide as immoral. The suicide in the old age was regarded under the different aspects of old age  and his positive and negative evaluation. As predecessor of the absolute refusal of suicide in the Christian era can be mentioned Cicero, who had regarded suicide in a special paper on the old age as the desertion without order of the commander-in-chief. However with the renaissance this attitude against the suicide changed and now the first time in the Christian era the possibility was discussed that very dangerously ill patients could end their pains by suicide. In the time of enlightenment more and more people thought, that very much cases of suicide were committed in severe illness. Especially suicide in the old age was regarded more and more as a psychiatric problem. There were new aspects contributed by medical statistics which could shown clearly the increase of tendency to suicide in the higher age of men. Today the question is vividly discussed if suicide in the old age is more the result of special environmental factors in the sense of isolation or economic instability or is produced by pathological processes in the brain such as cerebral sclerosis.", "contents": "[Historical aspects of suicide in the old age (author's transl)]. Beginning with a very different attitude of the antiquity taken up to suicide, which was normally not regarded as a self-murdering but as a voluntary departing this life and as such as a philosophically based act of liberty especially by members of the stoic system who not seldom commited suicide themselves, another estimation is discussed which was exercised by the Pythagoreans and the members of the Aristotele's doctrine. They rejected suicide as immoral. The suicide in the old age was regarded under the different aspects of old age  and his positive and negative evaluation. As predecessor of the absolute refusal of suicide in the Christian era can be mentioned Cicero, who had regarded suicide in a special paper on the old age as the desertion without order of the commander-in-chief. However with the renaissance this attitude against the suicide changed and now the first time in the Christian era the possibility was discussed that very dangerously ill patients could end their pains by suicide. In the time of enlightenment more and more people thought, that very much cases of suicide were committed in severe illness. Especially suicide in the old age was regarded more and more as a psychiatric problem. There were new aspects contributed by medical statistics which could shown clearly the increase of tendency to suicide in the higher age of men. Today the question is vividly discussed if suicide in the old age is more the result of special environmental factors in the sense of isolation or economic instability or is produced by pathological processes in the brain such as cerebral sclerosis."}
{"id": "PMID:26235", "title": "[Causes, motivations and tendencies of suicidal acts in old age (author's transl)].", "content": "The conditioning problems of suicidal acts of aged people were described by demonstrating the results of investigations in 125 patients (over 65 years). The control group consisted of 3004 suicidal patients below 65 years. Depression has been the prevailing psychiatric diagnosis (50% in contrast to 33% in the control group). 24% of the patients alleged conflicts with partners or other relatives as a motivation for the suicidal act. Fear of somatic illness or social isolation follows next. It is remarkable that vocational or economical conflicts were not mentioned. At last prevention problems were discussed. The need for modifying the attitude toward the aged was stressed.", "contents": "[Causes, motivations and tendencies of suicidal acts in old age (author's transl)]. The conditioning problems of suicidal acts of aged people were described by demonstrating the results of investigations in 125 patients (over 65 years). The control group consisted of 3004 suicidal patients below 65 years. Depression has been the prevailing psychiatric diagnosis (50% in contrast to 33% in the control group). 24% of the patients alleged conflicts with partners or other relatives as a motivation for the suicidal act. Fear of somatic illness or social isolation follows next. It is remarkable that vocational or economical conflicts were not mentioned. At last prevention problems were discussed. The need for modifying the attitude toward the aged was stressed."}
{"id": "PMID:26236", "title": "[Social psychological aspects of suicide in the old age (author's transl)].", "content": "Referring to Emile Durkheim's classical appraoch the normative aspects of suicide are emphasized, regarding suicidal behavior not as a purely individual phenomenon but as always co-determined by the normative expectations of a person's social environment. Starting from the dramatic increase of suicide rates with age combined with a marked decrease in non-letal suicide attempts it is argued that normally suicide-inhibiting social norms become less effective as a person appraoches old age, thus weakening the appellative motivation components of suicidal behavior and strengthening evasive strivings. Results of 2 representative studies are reported which tend to support these as well as a number of more specific hypotheses. Moreover, some aspects in the attitude to younger persons to suicidal acts of old people seem even compatible with the assumption of latent suicide-facilitating expectations.", "contents": "[Social psychological aspects of suicide in the old age (author's transl)]. Referring to Emile Durkheim's classical appraoch the normative aspects of suicide are emphasized, regarding suicidal behavior not as a purely individual phenomenon but as always co-determined by the normative expectations of a person's social environment. Starting from the dramatic increase of suicide rates with age combined with a marked decrease in non-letal suicide attempts it is argued that normally suicide-inhibiting social norms become less effective as a person appraoches old age, thus weakening the appellative motivation components of suicidal behavior and strengthening evasive strivings. Results of 2 representative studies are reported which tend to support these as well as a number of more specific hypotheses. Moreover, some aspects in the attitude to younger persons to suicidal acts of old people seem even compatible with the assumption of latent suicide-facilitating expectations."}
{"id": "PMID:26237", "title": "[Isolation, loneliness and suicidal ideas in the aged (author's transl)].", "content": "The relationship between various dimensions of social isolation, loneliness and suicidal ideas among a group of 406 respondents over 65 years of age were analyzed. The survey findings show that suicidal ideas emerge as a result of both, a loss of or a social denial to intimate and highly valued personal relationships. Generally, these suicidal ideas are connected to feelings of loneliness which are unrelated to the quantity of other social contacts. It seems to be of particular relevance whether the disengagement occurred voluntarily and whether the personal life style showed consistency of persistency resp. Based on these findings the fundamental problems of a social psychological approach to gerontology are discussed. These problems arise out of the more or less perfect correspondence between objective indicators of a social situation and its subjective correlates.", "contents": "[Isolation, loneliness and suicidal ideas in the aged (author's transl)]. The relationship between various dimensions of social isolation, loneliness and suicidal ideas among a group of 406 respondents over 65 years of age were analyzed. The survey findings show that suicidal ideas emerge as a result of both, a loss of or a social denial to intimate and highly valued personal relationships. Generally, these suicidal ideas are connected to feelings of loneliness which are unrelated to the quantity of other social contacts. It seems to be of particular relevance whether the disengagement occurred voluntarily and whether the personal life style showed consistency of persistency resp. Based on these findings the fundamental problems of a social psychological approach to gerontology are discussed. These problems arise out of the more or less perfect correspondence between objective indicators of a social situation and its subjective correlates."}
{"id": "PMID:26239", "title": "[Trends in modern international gerontological research. Experimental aspects].", "content": "In a personal statement the author takes the view that gerontology and geriatrics deal with the same fundamental biological phenomenon, namely loss of adaptability and of the capacity to maintain the parameters of homeostasis. Two focal points of recent research in gerontology are cell cultures and the central nervous system. Work with cell cultures has so far been unexpectedly disappointing as far as basic understanding of the ageing process in vivo is concerned. Biochemical, morphological, physiological and pharmacological investigations into the ageing brain have on the other hand provided a wealth of new data which promise major insights into basic mechanisms of the ageing process. Aim of all gerontologocal research must be an \"old age worth living\" rather than a speculative search for a prolongation of lifespan.", "contents": "[Trends in modern international gerontological research. Experimental aspects]. In a personal statement the author takes the view that gerontology and geriatrics deal with the same fundamental biological phenomenon, namely loss of adaptability and of the capacity to maintain the parameters of homeostasis. Two focal points of recent research in gerontology are cell cultures and the central nervous system. Work with cell cultures has so far been unexpectedly disappointing as far as basic understanding of the ageing process in vivo is concerned. Biochemical, morphological, physiological and pharmacological investigations into the ageing brain have on the other hand provided a wealth of new data which promise major insights into basic mechanisms of the ageing process. Aim of all gerontologocal research must be an \"old age worth living\" rather than a speculative search for a prolongation of lifespan."}
{"id": "PMID:26240", "title": "[Trends in modern international gerontological research. Epidemiological aspects].", "content": "Using the methods of comparing statistical data from the population in different countries on should have in mind that the age distribution could differ very much according to her biological and social structure. As example serves the system of social indicators applied by several supranational bodies in order to develop an instrument for measure the \"quality of life\". Life expectancy and and disability rates in different age groups are among those methods. National statistics do not use only mortability rates and to some extend also morbidity rates but also scaled values about the amount of activities in daily living. Sociomedical figures like the number of restricted-activity, bed-disability, school-loss, and workloss days per person per year seem to give more appropriate data for this purpose than the biomedical counts of the past. On would recognize--at least in the angloamerican countries--that there is a newer trend to find indicators for epidemiological studies and statistics applicable by non-medical personnel as disability components for an index of health in age.", "contents": "[Trends in modern international gerontological research. Epidemiological aspects]. Using the methods of comparing statistical data from the population in different countries on should have in mind that the age distribution could differ very much according to her biological and social structure. As example serves the system of social indicators applied by several supranational bodies in order to develop an instrument for measure the \"quality of life\". Life expectancy and and disability rates in different age groups are among those methods. National statistics do not use only mortability rates and to some extend also morbidity rates but also scaled values about the amount of activities in daily living. Sociomedical figures like the number of restricted-activity, bed-disability, school-loss, and workloss days per person per year seem to give more appropriate data for this purpose than the biomedical counts of the past. On would recognize--at least in the angloamerican countries--that there is a newer trend to find indicators for epidemiological studies and statistics applicable by non-medical personnel as disability components for an index of health in age."}
{"id": "PMID:26241", "title": "[Trends in modern international gerontological research. Psychological aspects].", "content": "The present paper is based on the analysis of congress reports and gerontological journals and points up new trends in gerontological research. Quantitatively, there was an increase in the number of psycho-gerontological publications. However, relatively seen, they represent an almost unchanged percentage of the contributions to gerontological literature on the whole. Predominant themes in USA and West Germany are discussed. There is, on the one hand, an increasing differentiation and specialization of methodical contribution and, on the other hand, an increasing number of contributions which neglect the methodical aspect. A trend toward practically oriented research is shown, as can be seen in intervention gerontology. Aging is seen as a phanomena with biological, social, and ecological determinants. In conclusion the universality and generality of aging is questioned, the concept of a differential gerontology is proposed and so a greater consideration of the individuality of the aging process is found to be necessary.", "contents": "[Trends in modern international gerontological research. Psychological aspects]. The present paper is based on the analysis of congress reports and gerontological journals and points up new trends in gerontological research. Quantitatively, there was an increase in the number of psycho-gerontological publications. However, relatively seen, they represent an almost unchanged percentage of the contributions to gerontological literature on the whole. Predominant themes in USA and West Germany are discussed. There is, on the one hand, an increasing differentiation and specialization of methodical contribution and, on the other hand, an increasing number of contributions which neglect the methodical aspect. A trend toward practically oriented research is shown, as can be seen in intervention gerontology. Aging is seen as a phanomena with biological, social, and ecological determinants. In conclusion the universality and generality of aging is questioned, the concept of a differential gerontology is proposed and so a greater consideration of the individuality of the aging process is found to be necessary."}
{"id": "PMID:26242", "title": "[Trends in modern international gerontological research. Sociological aspects].", "content": "Some new trends of the following theoretical models of the sociology of aging are discussed: 1. Models of life cycle which allow a clearer differentiation between the age groupings. 2. The logic of the scientific analysis and the lack of further analysis of the specific sociological content of the disengagement theory. 3. Quantitative and qualitative aspects of roles in the old age and age cohorts. 4. The significance of exchange-theory to analyse the special social situation of the elderly. 5. New results discussing the situation of the elderly as a minority group or subculture. 6. Organisational analysis of the welfare programs of the elderly.", "contents": "[Trends in modern international gerontological research. Sociological aspects]. Some new trends of the following theoretical models of the sociology of aging are discussed: 1. Models of life cycle which allow a clearer differentiation between the age groupings. 2. The logic of the scientific analysis and the lack of further analysis of the specific sociological content of the disengagement theory. 3. Quantitative and qualitative aspects of roles in the old age and age cohorts. 4. The significance of exchange-theory to analyse the special social situation of the elderly. 5. New results discussing the situation of the elderly as a minority group or subculture. 6. Organisational analysis of the welfare programs of the elderly."}
{"id": "PMID:26243", "title": "[Trends in modern international gerontological research. Psychiatric aspects].", "content": "The author puts a survey of new books, book's contributions, and recurrent publications of Geropsychiatry in last years. Special extracts are engaged with epidemiological investigations, clinical and diagnostical factors of presenile and senile dementia, and longitudinal studies of depressive disorders and schizophrenia. Sexual deviations, problems of therapy (Lithium, psychotherapy), and problems of expert opinion in older age are reported.", "contents": "[Trends in modern international gerontological research. Psychiatric aspects]. The author puts a survey of new books, book's contributions, and recurrent publications of Geropsychiatry in last years. Special extracts are engaged with epidemiological investigations, clinical and diagnostical factors of presenile and senile dementia, and longitudinal studies of depressive disorders and schizophrenia. Sexual deviations, problems of therapy (Lithium, psychotherapy), and problems of expert opinion in older age are reported."}
{"id": "PMID:26244", "title": "[Trends in modern international gerontological research. Morphological aspects].", "content": "Ageing develops during the whole life with differences on cells, tissues and organs, and begins if their capacities for adaptations and compensations decrease. Theories about ageing are insufficiently. That results from the further development of ageing research in morphology also. Parenchymal cells are reduced in all organs, in favour of an enhanced connective tissue content, the function of the single parenchymal and mesenchymal cell is not diminished coincidently in ageing. In the most organs are young and old cells in every age stage (but more old cells in senile age). The most cells don't live endless, but they can be regenerated. Their organelles possess own biological half life times, which are very shorter than their cell life times. Ageing-typical increase of the total content of connective tissue, esp. of collagen in many organs is combined with alterations of the proteoglycan and collagen metaoblism rates and patterns (collagen types included), and are thereby connected with age dependent changes of the several functions of the cells, tissues and organs. Everybody, and esp. the physician has to know that the mean age of the population (and of the patients) becomes higher. So we need the morphological research in gerontology also, as demonstrated and summarized in this review.", "contents": "[Trends in modern international gerontological research. Morphological aspects]. Ageing develops during the whole life with differences on cells, tissues and organs, and begins if their capacities for adaptations and compensations decrease. Theories about ageing are insufficiently. That results from the further development of ageing research in morphology also. Parenchymal cells are reduced in all organs, in favour of an enhanced connective tissue content, the function of the single parenchymal and mesenchymal cell is not diminished coincidently in ageing. In the most organs are young and old cells in every age stage (but more old cells in senile age). The most cells don't live endless, but they can be regenerated. Their organelles possess own biological half life times, which are very shorter than their cell life times. Ageing-typical increase of the total content of connective tissue, esp. of collagen in many organs is combined with alterations of the proteoglycan and collagen metaoblism rates and patterns (collagen types included), and are thereby connected with age dependent changes of the several functions of the cells, tissues and organs. Everybody, and esp. the physician has to know that the mean age of the population (and of the patients) becomes higher. So we need the morphological research in gerontology also, as demonstrated and summarized in this review."}
{"id": "PMID:26245", "title": "[Glucose absorption from the small intestine in rats of different ages (authors transl)].", "content": "Glucose absorption from the ageing rat's small intestine was studied \"in vivo\" using the recirculation-perfusion method of Sheff and Smyth. Different initial concentrations were used and animals of various ages (6 mo., 12 mo. and more than 27 mo. old) tested for their glucose uptake from the total small intestine (including duodenum) in the course of a twenty-minute period. Glucose was estimated by the modified o-toluidine method of Hultman. The (reciprocal) absorption data, reduced on dried intestine weight units were plotted by the Lineweaver -- Burk (regression) equations and the Km and Vmax indices derived. The results show that there is an apparent increase of the Km value in case of the old rats. Regarding the Km as an apparent affinity constant of the glucose for the carrier transport, ageing induces a considerable loss in affinity and a concomitant increase of the maximum absorptive capacity (Vmax) possible by the transfer capacity of the ageing small gut. The interpretation of the data suggest that the role of the probable age-dependent changes of diffusion-components cannot be ruled out.", "contents": "[Glucose absorption from the small intestine in rats of different ages (authors transl)]. Glucose absorption from the ageing rat's small intestine was studied \"in vivo\" using the recirculation-perfusion method of Sheff and Smyth. Different initial concentrations were used and animals of various ages (6 mo., 12 mo. and more than 27 mo. old) tested for their glucose uptake from the total small intestine (including duodenum) in the course of a twenty-minute period. Glucose was estimated by the modified o-toluidine method of Hultman. The (reciprocal) absorption data, reduced on dried intestine weight units were plotted by the Lineweaver -- Burk (regression) equations and the Km and Vmax indices derived. The results show that there is an apparent increase of the Km value in case of the old rats. Regarding the Km as an apparent affinity constant of the glucose for the carrier transport, ageing induces a considerable loss in affinity and a concomitant increase of the maximum absorptive capacity (Vmax) possible by the transfer capacity of the ageing small gut. The interpretation of the data suggest that the role of the probable age-dependent changes of diffusion-components cannot be ruled out."}
{"id": "PMID:26246", "title": "Bone mineral content of the healthy aged.", "content": "Using Norland-Cameron photon-absorption technique, bone mineral content of 436 healthy aged was measured and compared with that of 198 healthy, aged 21-50. Bone mineral content of postmenopausal females decreased continuously with age and bone mineral content of males began to decrease at age over 70. Bone width and menopausal age seemed to be important factors influencing bone mineral content, but previous physical activity seemed to have no effect on the bone mineral content of the aged.", "contents": "Bone mineral content of the healthy aged. Using Norland-Cameron photon-absorption technique, bone mineral content of 436 healthy aged was measured and compared with that of 198 healthy, aged 21-50. Bone mineral content of postmenopausal females decreased continuously with age and bone mineral content of males began to decrease at age over 70. Bone width and menopausal age seemed to be important factors influencing bone mineral content, but previous physical activity seemed to have no effect on the bone mineral content of the aged."}
{"id": "PMID:26247", "title": "Gerontological aspects of hyperostosis frontalis interna.", "content": "Authors discuss hyperostosis frontalis interna observed in a large number of aged persons, on the basis of age and sex distribution as well as its clinical and roentgenomorphological analysis. In various forms of the ossification of the frontal bone no significant difference was found between the localisation of hyperostosis and the clinical symptoms. On other hand, there is a direct correlation between the extension and severity of hyperostosis and the frequency of occurence of the associated symptoms (obesity, hypertension). They found the aetiological classification more adequate than the morphological categorization of Moore. Their cases are discussed 1. as partial phenomenon of the Morgagni's syndrome; 2. as independent alteration, showing no other symptoms; 3. as transitionary forms inserted between the two groups mentioned above. They discuss also the question of senile, compensatory hyperostosis frontalis interna. On the basis of the study of a large autopsy material they support the opinion that there is a direct connection of this form with old age.", "contents": "Gerontological aspects of hyperostosis frontalis interna. Authors discuss hyperostosis frontalis interna observed in a large number of aged persons, on the basis of age and sex distribution as well as its clinical and roentgenomorphological analysis. In various forms of the ossification of the frontal bone no significant difference was found between the localisation of hyperostosis and the clinical symptoms. On other hand, there is a direct correlation between the extension and severity of hyperostosis and the frequency of occurence of the associated symptoms (obesity, hypertension). They found the aetiological classification more adequate than the morphological categorization of Moore. Their cases are discussed 1. as partial phenomenon of the Morgagni's syndrome; 2. as independent alteration, showing no other symptoms; 3. as transitionary forms inserted between the two groups mentioned above. They discuss also the question of senile, compensatory hyperostosis frontalis interna. On the basis of the study of a large autopsy material they support the opinion that there is a direct connection of this form with old age."}
{"id": "PMID:26248", "title": "[Further data on the isolation of the aged (authors transl)].", "content": "Author's studies performed on 100 aged persons over sixty revealed the factors which play a role in the decline of the interpersonal connections. From his results, he suggests two forms of the communication-decrease during senessence. One form is a factor of exogen origin, which comes into existence as a result of deprivation effects, respectively. On the other hand, the second one is of intra-individual origin, whose nature formed by special characteristics of personality. These are typical of the individual during whole life. Both forms verify that in certain cases favourable, compensating components must be taken into account, however, sometimes this effect could be inauspicious. Separating the two forms is of great importance from the point of geriatrics, as well.", "contents": "[Further data on the isolation of the aged (authors transl)]. Author's studies performed on 100 aged persons over sixty revealed the factors which play a role in the decline of the interpersonal connections. From his results, he suggests two forms of the communication-decrease during senessence. One form is a factor of exogen origin, which comes into existence as a result of deprivation effects, respectively. On the other hand, the second one is of intra-individual origin, whose nature formed by special characteristics of personality. These are typical of the individual during whole life. Both forms verify that in certain cases favourable, compensating components must be taken into account, however, sometimes this effect could be inauspicious. Separating the two forms is of great importance from the point of geriatrics, as well."}
{"id": "PMID:26249", "title": "Immuno-electronmicroscopic studies after influenza vaccination of young and old individuals.", "content": "Authors examined the lymphocytes of young and old individuals after influenza vaccination. They stated that membrane bound surface IgG and IgM were detectable on the lymphocytes and occasionally on lymphoblasts in both the old and young age groups. In both age-groups intracytoplasmic tubulo-reticular structures (TRS) were seen in the lymphocytes and lymphoblasts. In young individuals TRS was present in the peroxidase positive cells, in the contrary in old persons TRS was never found in cells with surface immunoglobulins. In the TRS themselves peroxidase positive IgG and IgM could be detected.", "contents": "Immuno-electronmicroscopic studies after influenza vaccination of young and old individuals. Authors examined the lymphocytes of young and old individuals after influenza vaccination. They stated that membrane bound surface IgG and IgM were detectable on the lymphocytes and occasionally on lymphoblasts in both the old and young age groups. In both age-groups intracytoplasmic tubulo-reticular structures (TRS) were seen in the lymphocytes and lymphoblasts. In young individuals TRS was present in the peroxidase positive cells, in the contrary in old persons TRS was never found in cells with surface immunoglobulins. In the TRS themselves peroxidase positive IgG and IgM could be detected."}
{"id": "PMID:26250", "title": "Autoantibodies in aged individuals.", "content": "Authors determined in 282 individuals autoantibodies in 132 T and B lymphozytes. Theirs results were as follows: 1. The frequency of the presence of autoantibodies increases with age. 2. In the presence of autoantibodies the absolute T and B lymphocyte counts of aged persons markedly decrease; the absolute T and B lymphozyte counts of young adult people do not change by existing autoantibodies. 3. There is a significant difference between the absolute T cell counts of aged and young adult age groups, both age-groups having autoantibodies. 4. Comparing the frequency of occurence of autoantibodies in aged healthy persons and in aged ones with cardiovascular changes and being in the habit of smoking and consuming alcohole, respectively, a significant difference could be demonstrated; in the latter group the frequency was much higher.", "contents": "Autoantibodies in aged individuals. Authors determined in 282 individuals autoantibodies in 132 T and B lymphozytes. Theirs results were as follows: 1. The frequency of the presence of autoantibodies increases with age. 2. In the presence of autoantibodies the absolute T and B lymphocyte counts of aged persons markedly decrease; the absolute T and B lymphozyte counts of young adult people do not change by existing autoantibodies. 3. There is a significant difference between the absolute T cell counts of aged and young adult age groups, both age-groups having autoantibodies. 4. Comparing the frequency of occurence of autoantibodies in aged healthy persons and in aged ones with cardiovascular changes and being in the habit of smoking and consuming alcohole, respectively, a significant difference could be demonstrated; in the latter group the frequency was much higher."}
{"id": "PMID:26251", "title": "Age-related change of the absolute number of IgG-, and IgM-bearing B-lymphocytes and T-lymphocytes in human peripheral blood following influenza vaccination.", "content": "The absolute number of IgG-, and IgM-bearing B lymphocytes and of T lymphocytes was determined in the peripheral blood of 12 old (over 60 years) and 11 young (20 to 40 years) healthy persons before vaccination and 6 days and 6 weeks, respectively after vaccination. It has been found that as opposed to an approximately fivefold increase of IgG bearing cells in young persons, the increase did hardly reach double of the original value in old individuals. The absolute number of T lymphocytes participating in the immune reaction showed a transitory increase in young persons, while a gradual decrease has been observed in old individuals. In healthy elderly persons the administration of 10 U Honkong 5/72-B killed influenza virus as in vivo antigen stimulus resulted in a reduced proliferation of IgG carrier lymphocytes participating in antibody production.", "contents": "Age-related change of the absolute number of IgG-, and IgM-bearing B-lymphocytes and T-lymphocytes in human peripheral blood following influenza vaccination. The absolute number of IgG-, and IgM-bearing B lymphocytes and of T lymphocytes was determined in the peripheral blood of 12 old (over 60 years) and 11 young (20 to 40 years) healthy persons before vaccination and 6 days and 6 weeks, respectively after vaccination. It has been found that as opposed to an approximately fivefold increase of IgG bearing cells in young persons, the increase did hardly reach double of the original value in old individuals. The absolute number of T lymphocytes participating in the immune reaction showed a transitory increase in young persons, while a gradual decrease has been observed in old individuals. In healthy elderly persons the administration of 10 U Honkong 5/72-B killed influenza virus as in vivo antigen stimulus resulted in a reduced proliferation of IgG carrier lymphocytes participating in antibody production."}
{"id": "PMID:26252", "title": "Natural antibody level in old age.", "content": "Antibacterial antibodies were determined with a passive hemagglutination micromethod using the Boivin extract of eight different strains of bacteria. Correlation between antibody values of different specificities and between the summarized titer values and individual antibody titers were found. A significant decrease in the average of the summarized titer values was observed especially for persons over 70. The possibility of genetic regulation of normal antibody levels is suggested. The question whether the decrease in agglutinating antibody level in old age is due to the decreased activity of the corresponding immunocompetent cells or is secondary to other changes occuring in old age, is discussed.", "contents": "Natural antibody level in old age. Antibacterial antibodies were determined with a passive hemagglutination micromethod using the Boivin extract of eight different strains of bacteria. Correlation between antibody values of different specificities and between the summarized titer values and individual antibody titers were found. A significant decrease in the average of the summarized titer values was observed especially for persons over 70. The possibility of genetic regulation of normal antibody levels is suggested. The question whether the decrease in agglutinating antibody level in old age is due to the decreased activity of the corresponding immunocompetent cells or is secondary to other changes occuring in old age, is discussed."}
{"id": "PMID:26253", "title": "Influence of methyl xanthine treatment on calcitonin effect.", "content": "The presented results clearly demonstrate that theophylline, caffeine and theobromine have a blocking action on calcitonin effect as determined by the elevation of serum calcium level, although different degree of potency was found with each drugs. There is no difference in respect of the serum calcium elevation after a single dose of methyl xanthines or after a 9-10 day lasting treatment. The castration had no additional enhancing effect of the calcitonin resistance of methyl xanthine treated animals. The administration of androgens simultaneously with the methyl xanthine treatment failed to produce improvement of calcitonin sensitivty preventing the elevation of serum calcium after calcitonin injection. So the calcitonin resistance of methyl xanthine treated animals appears to be different to the calcitonin resistance of sex hormone deprived conditions because the latter could be abolished by androgen administration. Theophylline treatment resulted in a slightly but significantly elevated serum calcium comparing to controls without exogeneous calcitonin. This magnitude of elevation remains between the normocalcaemic limits.", "contents": "Influence of methyl xanthine treatment on calcitonin effect. The presented results clearly demonstrate that theophylline, caffeine and theobromine have a blocking action on calcitonin effect as determined by the elevation of serum calcium level, although different degree of potency was found with each drugs. There is no difference in respect of the serum calcium elevation after a single dose of methyl xanthines or after a 9-10 day lasting treatment. The castration had no additional enhancing effect of the calcitonin resistance of methyl xanthine treated animals. The administration of androgens simultaneously with the methyl xanthine treatment failed to produce improvement of calcitonin sensitivty preventing the elevation of serum calcium after calcitonin injection. So the calcitonin resistance of methyl xanthine treated animals appears to be different to the calcitonin resistance of sex hormone deprived conditions because the latter could be abolished by androgen administration. Theophylline treatment resulted in a slightly but significantly elevated serum calcium comparing to controls without exogeneous calcitonin. This magnitude of elevation remains between the normocalcaemic limits."}
{"id": "PMID:26254", "title": "[Survived brain infarction in old age - clinical and morphological findings. part I: extracranial stenoses of carotis arteries (author's transl)].", "content": "By clinical and post mortem findings we searched for the risk factors, important for brain infarctions in people of nearly 80 years. We were especially interested in the conditions of the extracranial vessels such as the carotid arteries and the murmurs at this point. The number of arterial stenoses in this region, ascertained in younger people is similar in old age. Besides of others factors, caused by old age, the many cases of multiple extracranial stenoses are probably responsible for the overproportional big brain infarctions in this series. In nearly 50% of all stenoses we heard vascular murmurs, mostly in both of the carotid arteries. Despite of some uncertainly of the clinical importance - just in old age many cardiac murmurs of the ejection type with tendency to transmission have been heard - they should give rise to investigate carefully the region of the neck in symptomatic patients.", "contents": "[Survived brain infarction in old age - clinical and morphological findings. part I: extracranial stenoses of carotis arteries (author's transl)]. By clinical and post mortem findings we searched for the risk factors, important for brain infarctions in people of nearly 80 years. We were especially interested in the conditions of the extracranial vessels such as the carotid arteries and the murmurs at this point. The number of arterial stenoses in this region, ascertained in younger people is similar in old age. Besides of others factors, caused by old age, the many cases of multiple extracranial stenoses are probably responsible for the overproportional big brain infarctions in this series. In nearly 50% of all stenoses we heard vascular murmurs, mostly in both of the carotid arteries. Despite of some uncertainly of the clinical importance - just in old age many cardiac murmurs of the ejection type with tendency to transmission have been heard - they should give rise to investigate carefully the region of the neck in symptomatic patients."}
{"id": "PMID:26255", "title": "[Iatrogenic depression in the aged (author's transl)].", "content": "The increasing number of depressions, especially in old patients, is alarming. Partly these depressions, however, are avoidable since they are of iatrogenic origin. By the example of hormones, antihypertensives, antihistaminics, antirheumatics and even the psychotropic drugs themselves the attention of physicians shall be called to substances which are a potential danger of depression.", "contents": "[Iatrogenic depression in the aged (author's transl)]. The increasing number of depressions, especially in old patients, is alarming. Partly these depressions, however, are avoidable since they are of iatrogenic origin. By the example of hormones, antihypertensives, antihistaminics, antirheumatics and even the psychotropic drugs themselves the attention of physicians shall be called to substances which are a potential danger of depression."}
{"id": "PMID:26256", "title": "[Laparoscopic findings in aged patients (author's transl)].", "content": "A group of 165 geriatric patients is compared with a control group of 114 younger patients concerning different frequency of laparoscopic diagnoses. As it was suspected from the clinical view aged patients predominently suffered from posthepatic cirrhosis and from cirrhosis of unknown origin, from recurrent cholecystitis, obstructive jaundice, metastases and carcinosis of peritoneal cavity. Younger patients much more frequently showed toxic liver damage starting from fatty liver and ending up with fatty liver cirrhosis. Persistent acute hepatitis non associated with HBSAg was scarcely seen with the aged group. It was a frequent diagnosis with the younger control group. There are explanations given for the differing endoscopic results concerning aged persons and younger control persons.", "contents": "[Laparoscopic findings in aged patients (author's transl)]. A group of 165 geriatric patients is compared with a control group of 114 younger patients concerning different frequency of laparoscopic diagnoses. As it was suspected from the clinical view aged patients predominently suffered from posthepatic cirrhosis and from cirrhosis of unknown origin, from recurrent cholecystitis, obstructive jaundice, metastases and carcinosis of peritoneal cavity. Younger patients much more frequently showed toxic liver damage starting from fatty liver and ending up with fatty liver cirrhosis. Persistent acute hepatitis non associated with HBSAg was scarcely seen with the aged group. It was a frequent diagnosis with the younger control group. There are explanations given for the differing endoscopic results concerning aged persons and younger control persons."}
{"id": "PMID:26257", "title": "[Results of a comparing study concerning men under 40 years old and above 60 years, affected by myocardial infarction (author's transl)].", "content": "We examined a group of 300 men in the age of under 40 and a comparing group of 300 men in the age of 60 and more years, with clinically or histologically ascertained heart infarct (according to criterions of (WHO). Our work brought the proof that clinically unambiguous heart-infarct in the group of men under 40 years was always connected with the following main risk-factors: 1. hear-infarct of sudden death under 60 years in the family anamnesis. 2. increased hypercholesterinaemy (6.708 mol/1), hypertriglyceridenaemy (2.0g/1) and hyperuricaemy (416.5 u mol/1). 3. Increased smoking of cigarettes (a day 20 cigarettes). Time since the beginning of the attack until ringing up the physician was found out to be longer in the group of men more than 60 years old. Noteworthy is also the age-dependence of the time of out-living after myocard-infarct.", "contents": "[Results of a comparing study concerning men under 40 years old and above 60 years, affected by myocardial infarction (author's transl)]. We examined a group of 300 men in the age of under 40 and a comparing group of 300 men in the age of 60 and more years, with clinically or histologically ascertained heart infarct (according to criterions of (WHO). Our work brought the proof that clinically unambiguous heart-infarct in the group of men under 40 years was always connected with the following main risk-factors: 1. hear-infarct of sudden death under 60 years in the family anamnesis. 2. increased hypercholesterinaemy (6.708 mol/1), hypertriglyceridenaemy (2.0g/1) and hyperuricaemy (416.5 u mol/1). 3. Increased smoking of cigarettes (a day 20 cigarettes). Time since the beginning of the attack until ringing up the physician was found out to be longer in the group of men more than 60 years old. Noteworthy is also the age-dependence of the time of out-living after myocard-infarct."}
{"id": "PMID:26258", "title": "Infectious mononucleosis in the case of two elderly (80 and 57 years old age) patients.", "content": "There are reported two cases of infectious mononucleosis in elderly. In the first case (80 years; probably the oldest in the geriatric literature) the infection provoked a very serious illness and the patient deceased three months after dimission, because of diminished resistance. In the second case the mononucleosis induced an autoimmune haemolytic anemia. The patient's daughter and granddaughter must be treated for complications of an infectious mononucleosis too.", "contents": "Infectious mononucleosis in the case of two elderly (80 and 57 years old age) patients. There are reported two cases of infectious mononucleosis in elderly. In the first case (80 years; probably the oldest in the geriatric literature) the infection provoked a very serious illness and the patient deceased three months after dimission, because of diminished resistance. In the second case the mononucleosis induced an autoimmune haemolytic anemia. The patient's daughter and granddaughter must be treated for complications of an infectious mononucleosis too."}
{"id": "PMID:26259", "title": "[Results concerning the sensitivity of old patients against digitalis (author's transl)].", "content": "It could be demonstrated that there was an age-dependent increase of digitalisintoxications in correlation with digitalisconcentrations in blood. This phenomenon can be explained with the frequently observed underweight in the senium. Some patients older than 70 years showed symptoms of intoxication in spite of a normal digitalisconcentration in serum. But the presented results did not demonstrate a significant difference between young and old patients concerning the sensitivity against digitalis. Therefore it is necessary to consider the bodyweight for digitalis therapy in older patients.", "contents": "[Results concerning the sensitivity of old patients against digitalis (author's transl)]. It could be demonstrated that there was an age-dependent increase of digitalisintoxications in correlation with digitalisconcentrations in blood. This phenomenon can be explained with the frequently observed underweight in the senium. Some patients older than 70 years showed symptoms of intoxication in spite of a normal digitalisconcentration in serum. But the presented results did not demonstrate a significant difference between young and old patients concerning the sensitivity against digitalis. Therefore it is necessary to consider the bodyweight for digitalis therapy in older patients."}
{"id": "PMID:26260", "title": "Treatment of painful osteoporosis with fluoride, calcium, and calciferol.", "content": "Fourteen women averaging 69.5 years of age with painful osteoporosis of the spine were treated with sodium fluoride, calcium salts and calciferol. At assessment after 5-19 months of therapy 8 patients were free of pains while in 5 women pains had decreased and mobility improved. One patient had unaltered pains. Side effects were few and mild.", "contents": "Treatment of painful osteoporosis with fluoride, calcium, and calciferol. Fourteen women averaging 69.5 years of age with painful osteoporosis of the spine were treated with sodium fluoride, calcium salts and calciferol. At assessment after 5-19 months of therapy 8 patients were free of pains while in 5 women pains had decreased and mobility improved. One patient had unaltered pains. Side effects were few and mild."}
{"id": "PMID:26261", "title": "[Age-related problems in the procedure of fibrinolytic treatment with streptokinase (author's transl)].", "content": "600 patients aged 24 to 78 were treated by streptokinase infusions. 38 patients were older and 562 patients younger than 65 years. Most indications of fibrinolytic therapy were chronic arterial occlusions and stenoses. The outcome of lytic treatment was dependent upon the occlusion's age, e.g., occlusions of 0--2 weeks standing were dissolvable in 75%, of 2--6 weeks standing in 57%, and of 6 weeks to 3 months standing in 38%. Very similar results were seen in iliac and aortic occlusions. Stenoses displaying crumbly irregular patterns in the angiogram responded as well to streptokinase infusion. No correlation between lytic success rate and patient's age was seen. Cerebral accidents occurring during fibrinolytic treatment amounted to 1.42% in the age group above 65 years and to 5.26% in the group under 65 years. This difference was significant at p less than 0.036.", "contents": "[Age-related problems in the procedure of fibrinolytic treatment with streptokinase (author's transl)]. 600 patients aged 24 to 78 were treated by streptokinase infusions. 38 patients were older and 562 patients younger than 65 years. Most indications of fibrinolytic therapy were chronic arterial occlusions and stenoses. The outcome of lytic treatment was dependent upon the occlusion's age, e.g., occlusions of 0--2 weeks standing were dissolvable in 75%, of 2--6 weeks standing in 57%, and of 6 weeks to 3 months standing in 38%. Very similar results were seen in iliac and aortic occlusions. Stenoses displaying crumbly irregular patterns in the angiogram responded as well to streptokinase infusion. No correlation between lytic success rate and patient's age was seen. Cerebral accidents occurring during fibrinolytic treatment amounted to 1.42% in the age group above 65 years and to 5.26% in the group under 65 years. This difference was significant at p less than 0.036."}
{"id": "PMID:26263", "title": "[Problems in teaching gerontological facts to medical students (author's transl)].", "content": "During the medical training the geriatric problems are still not observed enough, and they are not taken into consideration yet in the medical indexes for the different sections of the medical examination either. Geriatrics though, which have to be more extensive because of the multiplicity of the disease, can counteract to the necessary specialicing in the medical schools.", "contents": "[Problems in teaching gerontological facts to medical students (author's transl)]. During the medical training the geriatric problems are still not observed enough, and they are not taken into consideration yet in the medical indexes for the different sections of the medical examination either. Geriatrics though, which have to be more extensive because of the multiplicity of the disease, can counteract to the necessary specialicing in the medical schools."}
{"id": "PMID:26264", "title": "[Expectations of participants in gerontological in-service courses as a didactic problem (author's transl)].", "content": "In planning and teaching gerontological inservice courses one has to take into account the fact that the participants are adult learners who have certain expectations and interests. In the present article typical expectations are discussed and didactic conclusions for the future organization of in-service courses are drawn.", "contents": "[Expectations of participants in gerontological in-service courses as a didactic problem (author's transl)]. In planning and teaching gerontological inservice courses one has to take into account the fact that the participants are adult learners who have certain expectations and interests. In the present article typical expectations are discussed and didactic conclusions for the future organization of in-service courses are drawn."}
{"id": "PMID:26265", "title": "[Psychological determinants of motivation in adult education (author's transl)].", "content": "The psychology of motivation in adult education has been mostly confined to the assessment of superficial causes for attending courses and seminars. The findings were not integrated in a ced in a conclusive theory of motivation elaborated for instance by American and German psychologists. Besides that the verbalized \"motives\" to attend courses were hardly correlated with other psychological and social context variables. An investigation of the relationship between verbalized \"motives\" to attend courses, certain personality dimensions (Freiburg Personality Inventory) and some aspects of the \"life space\" (occupational and non-occupatoinal) revealed that the motivation to participate in adult education is embedded in the context of psychological and socio-demographic factors and that the motive structure depends on the relevance of life-long learning, for example, to keep or improve the occupational status or to meet people involved in creative activities.", "contents": "[Psychological determinants of motivation in adult education (author's transl)]. The psychology of motivation in adult education has been mostly confined to the assessment of superficial causes for attending courses and seminars. The findings were not integrated in a ced in a conclusive theory of motivation elaborated for instance by American and German psychologists. Besides that the verbalized \"motives\" to attend courses were hardly correlated with other psychological and social context variables. An investigation of the relationship between verbalized \"motives\" to attend courses, certain personality dimensions (Freiburg Personality Inventory) and some aspects of the \"life space\" (occupational and non-occupatoinal) revealed that the motivation to participate in adult education is embedded in the context of psychological and socio-demographic factors and that the motive structure depends on the relevance of life-long learning, for example, to keep or improve the occupational status or to meet people involved in creative activities."}
{"id": "PMID:26266", "title": "[Vocational training courses for personell in old age work--a problem- and participants-oriented education approach (author's transl)].", "content": "Working definitions of problem-oriented and participants-oriented approach in adult education. Planning problems in terms of needs and expectations of participants as central foci of approach; in terms of new role requirements requirements of learners and teachers; in terms of new objectives of learning such as behavioral changes as compared to information gathering. Report on three examples of courses for social workers and nursing personnell.", "contents": "[Vocational training courses for personell in old age work--a problem- and participants-oriented education approach (author's transl)]. Working definitions of problem-oriented and participants-oriented approach in adult education. Planning problems in terms of needs and expectations of participants as central foci of approach; in terms of new role requirements requirements of learners and teachers; in terms of new objectives of learning such as behavioral changes as compared to information gathering. Report on three examples of courses for social workers and nursing personnell."}
{"id": "PMID:26267", "title": "[Continuous education for people who work with the aged, especially for people who run homes for the aged (author's transl)].", "content": "In accordance with Paolo Freire learning is not only an intake of knowledge, but it is reflection of one's own life situation and finding of new solutions. The consequence for continuous education of people who run homes for the aged is that the process of learning has to be connected with the practical experience of the participants. The long termed course of continuous education for directors of homes for the aged therefore always starts with a definition of their tasks. That leads to a definition of learning goals, which will be approached by working out and following a planned schedule for the whole course.", "contents": "[Continuous education for people who work with the aged, especially for people who run homes for the aged (author's transl)]. In accordance with Paolo Freire learning is not only an intake of knowledge, but it is reflection of one's own life situation and finding of new solutions. The consequence for continuous education of people who run homes for the aged is that the process of learning has to be connected with the practical experience of the participants. The long termed course of continuous education for directors of homes for the aged therefore always starts with a definition of their tasks. That leads to a definition of learning goals, which will be approached by working out and following a planned schedule for the whole course."}
{"id": "PMID:26268", "title": "[Continuing education for social workers in the field of gerontology (author's transl)].", "content": "This article reports on a first attempt to integrate advanced training programs for social workers in the field of psycho-social gerontology into university curricula. The report concentrates on experience and problems to transmit and translate gerontological research results for the use of practitioners. Especially effective proved the integration of social workers as \"experts-in-practice\" into open-curricular-learning and their participation in application oriented research.", "contents": "[Continuing education for social workers in the field of gerontology (author's transl)]. This article reports on a first attempt to integrate advanced training programs for social workers in the field of psycho-social gerontology into university curricula. The report concentrates on experience and problems to transmit and translate gerontological research results for the use of practitioners. Especially effective proved the integration of social workers as \"experts-in-practice\" into open-curricular-learning and their participation in application oriented research."}
{"id": "PMID:26269", "title": "[Activating help--aims and limits (author's transl)].", "content": "The publication attempts to analyze current work directed at aiding and encouraging aged people in the Federal Republic of Germany, seen from the viewpoint of the various welfare associations, and hense from a practical angle. The considerable contrast between aims, available knowledge, and realization, is made clear by discussing individual problem fields while presenting a catalog of relevant and necessary measures. The paper also describes the requirements training and continuing education, as well as the need for research based on practice and yielding results which are relevant in the everyday life of the aged.", "contents": "[Activating help--aims and limits (author's transl)]. The publication attempts to analyze current work directed at aiding and encouraging aged people in the Federal Republic of Germany, seen from the viewpoint of the various welfare associations, and hense from a practical angle. The considerable contrast between aims, available knowledge, and realization, is made clear by discussing individual problem fields while presenting a catalog of relevant and necessary measures. The paper also describes the requirements training and continuing education, as well as the need for research based on practice and yielding results which are relevant in the everyday life of the aged."}
{"id": "PMID:26271", "title": "[Ageing and geriatric agents in the view of experimental gerontology (authors transl)].", "content": "Applying the research methods used in natural sciences and medicine and the concept of bionomy, it has been attempted to make basic statements about the process of aging. 140 geriatric agents have been examined with reference to the medications for their use, their connection with the aging process and particularly their effect on vitality. Finally it has been pointed out that test procedures for age parameters in experimental and clinical gerontology, which can be used in assessing geriatric agents, are in existence.", "contents": "[Ageing and geriatric agents in the view of experimental gerontology (authors transl)]. Applying the research methods used in natural sciences and medicine and the concept of bionomy, it has been attempted to make basic statements about the process of aging. 140 geriatric agents have been examined with reference to the medications for their use, their connection with the aging process and particularly their effect on vitality. Finally it has been pointed out that test procedures for age parameters in experimental and clinical gerontology, which can be used in assessing geriatric agents, are in existence."}
{"id": "PMID:26272", "title": "[Gerontological investigations of the nucleic acid metabolism in the rat. II. DNA repair capacity in different ages (authors transl)].", "content": "We tried to develop a model of in-vivo investigations into the DNA repair capacity of rats and, by means of this model, to determine the effect of age. To this end the DNA repair capacity was determined after gamma-irradiation with 3 groups of male white Sprague-Dawley rats aged 6, 18-20 and 32-34 months. The organs liver, kidney, heart and spleen were used for this investigation. The relative repair (RR) showed a discontinuous course both in the 4 organs, and in the 3 different age groups. We define \"relative repair\" as the relationship between the specific activity of DNA decomposition products and the specific activity of DNA in an irradiated test group, as compared with an unirradiated control group. In all age groups the course was similar in the liver and the spleen, especially in the young rats, as well as in the heart and the kidney. Age differences were seen to be significant in all 4 organs at particular intervals after the irradiation, which means that the maximum relative repair occurs at different times. The integration over the whole course of the investigation shows a distinct reduction in the relative repair with increasing age in all the investigated organs except the spleen, where we could not see a difference between the 2 older groups.", "contents": "[Gerontological investigations of the nucleic acid metabolism in the rat. II. DNA repair capacity in different ages (authors transl)]. We tried to develop a model of in-vivo investigations into the DNA repair capacity of rats and, by means of this model, to determine the effect of age. To this end the DNA repair capacity was determined after gamma-irradiation with 3 groups of male white Sprague-Dawley rats aged 6, 18-20 and 32-34 months. The organs liver, kidney, heart and spleen were used for this investigation. The relative repair (RR) showed a discontinuous course both in the 4 organs, and in the 3 different age groups. We define \"relative repair\" as the relationship between the specific activity of DNA decomposition products and the specific activity of DNA in an irradiated test group, as compared with an unirradiated control group. In all age groups the course was similar in the liver and the spleen, especially in the young rats, as well as in the heart and the kidney. Age differences were seen to be significant in all 4 organs at particular intervals after the irradiation, which means that the maximum relative repair occurs at different times. The integration over the whole course of the investigation shows a distinct reduction in the relative repair with increasing age in all the investigated organs except the spleen, where we could not see a difference between the 2 older groups."}
{"id": "PMID:26273", "title": "[Tensibility measurements on the rat's aorta III. Analysis of longitudinal and transversal extension as related to age (authors transl)].", "content": "Stress-strain diagrams of standardizised longitudinal and transversal stripes of the thoracic aorta of 125 male Sprague-Dawley rats aged 9, 15, 24 and 30 months were recorded by an electromechanical instrument. The stripes were subjected to three successive extension-relaxation cycles. The relaxation curves of the third cycle were approximated to the functions y = a + bx and y = cxd (longitudinal stripes) and y = mxf and y = gxh (transversal stripes) respectively. The parameters could be interpreted as measures for structural and functional properties of elastic and collagenous fibers. The age changes of the curve parameters led to the following conclusions concerning age-dependent functional alterations of the aorta: The emphasis can be placed upon the increasing resistance counteracting the extension occuring with great stroke volumes. This may lead to the reduction of the capacity of the air chamber with great stroke volumes. These phenomena seem to be mainly caused by an increase of the pitch of the spiral of the collagenic fiber and the increase of the amount and/or the stability of the collagen. Age-related alterations of the elastin and of the net structure formed by the fibers influence also the distensibility at smaller extensions but seem to be less important. Therefore, the structural alterations of the aorta with age will affect the function in the first place at large stroke volumes and not be very obvious at a basic heart performance.", "contents": "[Tensibility measurements on the rat's aorta III. Analysis of longitudinal and transversal extension as related to age (authors transl)]. Stress-strain diagrams of standardizised longitudinal and transversal stripes of the thoracic aorta of 125 male Sprague-Dawley rats aged 9, 15, 24 and 30 months were recorded by an electromechanical instrument. The stripes were subjected to three successive extension-relaxation cycles. The relaxation curves of the third cycle were approximated to the functions y = a + bx and y = cxd (longitudinal stripes) and y = mxf and y = gxh (transversal stripes) respectively. The parameters could be interpreted as measures for structural and functional properties of elastic and collagenous fibers. The age changes of the curve parameters led to the following conclusions concerning age-dependent functional alterations of the aorta: The emphasis can be placed upon the increasing resistance counteracting the extension occuring with great stroke volumes. This may lead to the reduction of the capacity of the air chamber with great stroke volumes. These phenomena seem to be mainly caused by an increase of the pitch of the spiral of the collagenic fiber and the increase of the amount and/or the stability of the collagen. Age-related alterations of the elastin and of the net structure formed by the fibers influence also the distensibility at smaller extensions but seem to be less important. Therefore, the structural alterations of the aorta with age will affect the function in the first place at large stroke volumes and not be very obvious at a basic heart performance."}
{"id": "PMID:26274", "title": "[The motor activity as an age parameter of the rat (authors transl)].", "content": "The motor activity as an behavioural parameter provides information about the functional state of the organism as a whole. Therefore it is an important age parameter. The results of activity measurements, however, depend strongly on the method of registration. Using 3 groups of male Sprague-Dawley rats aged 9, 15 and 29 months two methods have been tested: 1) An electronic recording: the rats were registrated in their normal cages on the Animex-Activity-Meter during the dark-phase in complete darkness. The activity measured by this method has been regarded as spontaneous activity. 2) A kinematographic method: the rats were registrated in a changed environment at constant light during the dark-phase. The activity assessed by this method has been regarded as reactive activity. Spontaneous and reactive activity show a different age dependence. For the use of the motor activity as an age parameter, both, spontaneous and reactive activity, should be assessed to get a better information about the ageing of the different functional levels of the systems governing the animal's behaviour.", "contents": "[The motor activity as an age parameter of the rat (authors transl)]. The motor activity as an behavioural parameter provides information about the functional state of the organism as a whole. Therefore it is an important age parameter. The results of activity measurements, however, depend strongly on the method of registration. Using 3 groups of male Sprague-Dawley rats aged 9, 15 and 29 months two methods have been tested: 1) An electronic recording: the rats were registrated in their normal cages on the Animex-Activity-Meter during the dark-phase in complete darkness. The activity measured by this method has been regarded as spontaneous activity. 2) A kinematographic method: the rats were registrated in a changed environment at constant light during the dark-phase. The activity assessed by this method has been regarded as reactive activity. Spontaneous and reactive activity show a different age dependence. For the use of the motor activity as an age parameter, both, spontaneous and reactive activity, should be assessed to get a better information about the ageing of the different functional levels of the systems governing the animal's behaviour."}
{"id": "PMID:26275", "title": "[Time-dependent functions of the age course of age parameters of the rat (authors transl)].", "content": "Using 136 male Sprague-Dawley rats of various ages, the ageing functions of parameters originating from different organisation levels of the organism were determined. The parameters which were investigated on different levels show a non linear time dependence which can be approximated by simple or composed exponential decay-functions or by rising logarithmic functions. The results suggest a logarithmic relation between biological and chronological age.", "contents": "[Time-dependent functions of the age course of age parameters of the rat (authors transl)]. Using 136 male Sprague-Dawley rats of various ages, the ageing functions of parameters originating from different organisation levels of the organism were determined. The parameters which were investigated on different levels show a non linear time dependence which can be approximated by simple or composed exponential decay-functions or by rising logarithmic functions. The results suggest a logarithmic relation between biological and chronological age."}
{"id": "PMID:26276", "title": "The age-dependent effect of caffeine on the plasma noradrenaline content in white mice.", "content": "The level of noradrenaline (NA) in the plasma of white mice, determined radioenzymatically as described by Henry et al. changes with age. In 45 days old animals NA in plasma is 10.3 +/- 4.4 ng/ml, whereas in 220 days old animals it was found to be 22.7 +/- 8.8 ng/ml. In 45 days old animals NA in plasma is increased 30 min after caffeine (45 microgram/g) significantly to 109% of control level, whereas in the older animals it is raised insignificantly (14%). The observed NA increase in plasma with increasing age might be a compensatory reaction due to diminished sensibility of the postsynaptic adrenergic receptors to NA. The explanation for the missing raise in NA plasma level after caffeine in adult mice might be the following: Calcium ions are indispensable for the release of NA by nerve impulses and the stimulation of presynaptic beta-receptors of noradrenergic neurons by NA contributes to facilitations of NA release. As in older animals under physiological conditions the release of NA is higher than in young animals it can be assumed that in the older ones the NA release from sympathetic neurons stimulated by caffeine cannot be further enhanced since the calcium receptors are fully occupied by released calcium ions and the presynaptic beta-receptors by released NA molecules.", "contents": "The age-dependent effect of caffeine on the plasma noradrenaline content in white mice. The level of noradrenaline (NA) in the plasma of white mice, determined radioenzymatically as described by Henry et al. changes with age. In 45 days old animals NA in plasma is 10.3 +/- 4.4 ng/ml, whereas in 220 days old animals it was found to be 22.7 +/- 8.8 ng/ml. In 45 days old animals NA in plasma is increased 30 min after caffeine (45 microgram/g) significantly to 109% of control level, whereas in the older animals it is raised insignificantly (14%). The observed NA increase in plasma with increasing age might be a compensatory reaction due to diminished sensibility of the postsynaptic adrenergic receptors to NA. The explanation for the missing raise in NA plasma level after caffeine in adult mice might be the following: Calcium ions are indispensable for the release of NA by nerve impulses and the stimulation of presynaptic beta-receptors of noradrenergic neurons by NA contributes to facilitations of NA release. As in older animals under physiological conditions the release of NA is higher than in young animals it can be assumed that in the older ones the NA release from sympathetic neurons stimulated by caffeine cannot be further enhanced since the calcium receptors are fully occupied by released calcium ions and the presynaptic beta-receptors by released NA molecules."}
{"id": "PMID:26299", "title": "Advantages and disadvantages of beta-adrenergic blocking drugs in hypertension.", "content": "This paper reviews the role of beta-adrenergic blocking drugs in the treatment of hypertension. A significant proportion of patients presenting with mild or moderate hypertension will respond to general measures and do not require specific drug therapy. Of the remaining patients, some will respond to treatment with a thiazide diuretic alone, and those with severe grades of hypertension will require the addition of a beta-adrenergic blocking drug, occasionally together with a vasodilator. The advantages of beta-adrenergic lbocking drugs alone or in combination and the problems associated with therapy are discussed.", "contents": "Advantages and disadvantages of beta-adrenergic blocking drugs in hypertension. This paper reviews the role of beta-adrenergic blocking drugs in the treatment of hypertension. A significant proportion of patients presenting with mild or moderate hypertension will respond to general measures and do not require specific drug therapy. Of the remaining patients, some will respond to treatment with a thiazide diuretic alone, and those with severe grades of hypertension will require the addition of a beta-adrenergic blocking drug, occasionally together with a vasodilator. The advantages of beta-adrenergic lbocking drugs alone or in combination and the problems associated with therapy are discussed."}
{"id": "PMID:26300", "title": "[Fluorometric determination of free and total tryptophan in blood plasma].", "content": "Free and total tryptophan is estimated in the plasma by a spectrofluorimetric method using an amplification reaction and fluorescence by transformation of tryptophan into norharman using formalin and perhydrol (fluorescence is amplified about 15 times). Free tryptophan in the plasma is separated by ultrafiltration under pressure. We verified the analytical characteristics of the method in order to obtain optimal conditions. Values frequently found in 16 blood donors in good health were 10.4 +/- 3.3 micronmol/l. for free tryptophan (average +/- ts for a risk of 5%) and 54.6 +/- 18.6 micronmol/l. for total tryptophan.", "contents": "[Fluorometric determination of free and total tryptophan in blood plasma]. Free and total tryptophan is estimated in the plasma by a spectrofluorimetric method using an amplification reaction and fluorescence by transformation of tryptophan into norharman using formalin and perhydrol (fluorescence is amplified about 15 times). Free tryptophan in the plasma is separated by ultrafiltration under pressure. We verified the analytical characteristics of the method in order to obtain optimal conditions. Values frequently found in 16 blood donors in good health were 10.4 +/- 3.3 micronmol/l. for free tryptophan (average +/- ts for a risk of 5%) and 54.6 +/- 18.6 micronmol/l. for total tryptophan."}
{"id": "PMID:26302", "title": "Control of lung surfactant by ventilation, adrenergic mediators, and prostaglandins in the rabbit.", "content": "In a previous study, we showed that increasing minute ventilation (VE) in rabbit lung by adding a dead space augmented pulmonary surfactant in the airspaces by a cholinergically mediated mechanism. Using the same model in the present study of 148 rabbits, we found that increasing VE augmented airspace phospholipid, the main component of surfactant, from 2.50 +/- 0.61 (mean +/- SD) mg per g of lung during normal VE to 3.15 +/- 1.22 (mean +/- SD) mg per g of lung during increased VE (P = 0.02). Both blocking beta-adrenergic receptors with propranolol or sotalol and inhibiting prostaglandin synthetase with indomethacin or sodium meclofenamate prevented the expected increase in phospholipid during increased VE (P is less than 0.05). The beta-2 agonist, terbutaline, increased phospholipid by 43 per cent during normal VE (P is less than 0.01), and propranolol blocked this increase (P is less than 0.05). Isoproterenol, arachidonic acid, prostaglandins E1, E2, F2alpha, and a cyclic endoperoxide analog of prostaglandin H2 (U-46619) injected during normal VE failed to increase phospholipid. We concluded that acetylcholine (previous study), beta-adrenergic mediators, and prostaglandins are involved in controlling alveolar surfactant during increased VE.", "contents": "Control of lung surfactant by ventilation, adrenergic mediators, and prostaglandins in the rabbit. In a previous study, we showed that increasing minute ventilation (VE) in rabbit lung by adding a dead space augmented pulmonary surfactant in the airspaces by a cholinergically mediated mechanism. Using the same model in the present study of 148 rabbits, we found that increasing VE augmented airspace phospholipid, the main component of surfactant, from 2.50 +/- 0.61 (mean +/- SD) mg per g of lung during normal VE to 3.15 +/- 1.22 (mean +/- SD) mg per g of lung during increased VE (P = 0.02). Both blocking beta-adrenergic receptors with propranolol or sotalol and inhibiting prostaglandin synthetase with indomethacin or sodium meclofenamate prevented the expected increase in phospholipid during increased VE (P is less than 0.05). The beta-2 agonist, terbutaline, increased phospholipid by 43 per cent during normal VE (P is less than 0.01), and propranolol blocked this increase (P is less than 0.05). Isoproterenol, arachidonic acid, prostaglandins E1, E2, F2alpha, and a cyclic endoperoxide analog of prostaglandin H2 (U-46619) injected during normal VE failed to increase phospholipid. We concluded that acetylcholine (previous study), beta-adrenergic mediators, and prostaglandins are involved in controlling alveolar surfactant during increased VE."}
{"id": "PMID:26303", "title": "[A short loading acidificacion test with calcium chloride in infants (author's transl)].", "content": "The response of blood and kidney to orally administered CaCl2 (4.1 mEq. X Kg.) in a short acid loading was compared to that attained with standard agent NH4Cl (3.9 mEq. X Kg) in two groups of normal infants through a 6 hrs. period. Plasma pH and bicarbonate decreased significantly. Minimum urine pH was 5.0 o lesser in all infants. Decrease of urine pH was greater to CaCl2 than to NH4Cl group but the net hydrogen ion excretion by the kidney was minor. Accordingly this experience CaCl2 can replace NH4Cl as acidifying substance in a short acid loading test. Indication will be diffuse hepatic lesions rendering dangerous NH4Cl administration.", "contents": "[A short loading acidificacion test with calcium chloride in infants (author's transl)]. The response of blood and kidney to orally administered CaCl2 (4.1 mEq. X Kg.) in a short acid loading was compared to that attained with standard agent NH4Cl (3.9 mEq. X Kg) in two groups of normal infants through a 6 hrs. period. Plasma pH and bicarbonate decreased significantly. Minimum urine pH was 5.0 o lesser in all infants. Decrease of urine pH was greater to CaCl2 than to NH4Cl group but the net hydrogen ion excretion by the kidney was minor. Accordingly this experience CaCl2 can replace NH4Cl as acidifying substance in a short acid loading test. Indication will be diffuse hepatic lesions rendering dangerous NH4Cl administration."}
{"id": "PMID:26307", "title": "[Extraction and polarimetric method of determining phenacetyl-D(-)-alpha-aminophenylacetic acid].", "content": "Equilibrium distribution of phenacetyl-D-(--)-alpha-aminophenylacetic acid obtained on fermentative hydrolysis of D,L-aminophenylacetic acid in a two-phase system (chloroform-water) was studied within a wide range of the substance concentration in the organic phase. It was shown than in the organic phase the distributing substance formed associates. The empirical equation: y = A + Bx describing the dependence of the effective distribution of the non-dissociated form of phenylacetyl-D-(--)-alpha-aminophenylacetic acid on its concentration in the organic phase was suggested. Coefficients A and B of the equation were determined and an equation for evaluating equilibrium concentrations in the equeous phase was suggested. On the basis of the studies an extraction-polarometric method for quantitative determination of phenacetyl-D-(--)-alpha-aminophenylacetic acid concentration was developed. The method consists of extraction of the non-dissociated form of phenylacetyl-D-(--)-alpha-aminophenylacetic acid with chloroform, determination of the equilibrium concentration of the distributing substance in the organic phase by the polarimetric method and subsequent estimation of the equilibrium and initial concentrations of the electrolyte in the aqueous phase.", "contents": "[Extraction and polarimetric method of determining phenacetyl-D(-)-alpha-aminophenylacetic acid]. Equilibrium distribution of phenacetyl-D-(--)-alpha-aminophenylacetic acid obtained on fermentative hydrolysis of D,L-aminophenylacetic acid in a two-phase system (chloroform-water) was studied within a wide range of the substance concentration in the organic phase. It was shown than in the organic phase the distributing substance formed associates. The empirical equation: y = A + Bx describing the dependence of the effective distribution of the non-dissociated form of phenylacetyl-D-(--)-alpha-aminophenylacetic acid on its concentration in the organic phase was suggested. Coefficients A and B of the equation were determined and an equation for evaluating equilibrium concentrations in the equeous phase was suggested. On the basis of the studies an extraction-polarometric method for quantitative determination of phenacetyl-D-(--)-alpha-aminophenylacetic acid concentration was developed. The method consists of extraction of the non-dissociated form of phenylacetyl-D-(--)-alpha-aminophenylacetic acid with chloroform, determination of the equilibrium concentration of the distributing substance in the organic phase by the polarimetric method and subsequent estimation of the equilibrium and initial concentrations of the electrolyte in the aqueous phase."}
{"id": "PMID:26308", "title": "Reisolation and growth conditions of bacillus agar-exedens.", "content": "Several agarolytic Bacillus strains have been isolated. The properties agree with those described by Wieringa (1941) for Bacillus agar-exedens. These strains are the first reisolates since the original cultures were lost. A second group of isolates is related to the agarolytic B. palustris var. gelaticus of Sickles and Shaw (1934). B. agar-exedens requires carbohydrates for growth. In mineral-glucose media growth is inhibited by peptone at pH values of about 7 or less. Under alkaline conditions no inhibition by peptone is observed. A method for the enrichment of B. agar-exedens is described.", "contents": "Reisolation and growth conditions of bacillus agar-exedens. Several agarolytic Bacillus strains have been isolated. The properties agree with those described by Wieringa (1941) for Bacillus agar-exedens. These strains are the first reisolates since the original cultures were lost. A second group of isolates is related to the agarolytic B. palustris var. gelaticus of Sickles and Shaw (1934). B. agar-exedens requires carbohydrates for growth. In mineral-glucose media growth is inhibited by peptone at pH values of about 7 or less. Under alkaline conditions no inhibition by peptone is observed. A method for the enrichment of B. agar-exedens is described."}
{"id": "PMID:26309", "title": "Inhibition of light-induced pH increase and O2 evolution of marine microalgae by water-soluble components of crude and refined oils.", "content": "Light-induced alkalinization of the extracellular medium was found to be a common feature of the primary photosynthetic process of several marine microalgae. The light-induce PH increase of suspensions of whole cells was immediately and severely inhibited by a single dose of water-soluble components from crude and fuel oils. Differential effects on the rates of microalgal photosynthetic O2 evolution and cell suspension pH increase suggest different toxicity mechanisms of the water-soluble components of no. 2 fuel oil as compared with Southern Louisiana and Jay Crude oils. These short-term studies on the nature of sublethal petroleum toxicity to microalgae indicate that the primary effect may be through direct action on the energy-yielding electron transport systems.", "contents": "Inhibition of light-induced pH increase and O2 evolution of marine microalgae by water-soluble components of crude and refined oils. Light-induced alkalinization of the extracellular medium was found to be a common feature of the primary photosynthetic process of several marine microalgae. The light-induce PH increase of suspensions of whole cells was immediately and severely inhibited by a single dose of water-soluble components from crude and fuel oils. Differential effects on the rates of microalgal photosynthetic O2 evolution and cell suspension pH increase suggest different toxicity mechanisms of the water-soluble components of no. 2 fuel oil as compared with Southern Louisiana and Jay Crude oils. These short-term studies on the nature of sublethal petroleum toxicity to microalgae indicate that the primary effect may be through direct action on the energy-yielding electron transport systems."}
{"id": "PMID:26310", "title": "Anaerobic utilization of phosphite and hypophosphite by Bacillus sp.", "content": "A Bacillus sp. capable of utilizing phosphite and hypophosphite under anaerobic conditions was isolated from Cape Canerval soil samples. The organism was isolated on a glucose-mineral salts medium with phosphate deleted. Anaerobic cultivation of this isolate resulted in decreases in the hypophosphite or phosphite concentration, increases in turbidity, cell count, and dry-cell weight, and decreases in pH and glucose concentration. The optimum hypophosphite concentration for this isolate was 60 microgram/ml, whereas the optimum phosphate concentration was greater than 1,000 microgram/ml, suggesting that higher concentrations of hypophosphite may be toxic to this isolate. Hypophosphite or phosphite utilization was accompanied by little or no detectable accumulation of phosphate in the medium, and 32P-labeled hypophosphite was incorporated into the cell as organic phosphate. When phosphate was present in the medium, the isolate failed to metabolize phosphite. In the presence of phosphite and hypophosphite, the isolate first utilized phosphite and then hypophosphite.", "contents": "Anaerobic utilization of phosphite and hypophosphite by Bacillus sp. A Bacillus sp. capable of utilizing phosphite and hypophosphite under anaerobic conditions was isolated from Cape Canerval soil samples. The organism was isolated on a glucose-mineral salts medium with phosphate deleted. Anaerobic cultivation of this isolate resulted in decreases in the hypophosphite or phosphite concentration, increases in turbidity, cell count, and dry-cell weight, and decreases in pH and glucose concentration. The optimum hypophosphite concentration for this isolate was 60 microgram/ml, whereas the optimum phosphate concentration was greater than 1,000 microgram/ml, suggesting that higher concentrations of hypophosphite may be toxic to this isolate. Hypophosphite or phosphite utilization was accompanied by little or no detectable accumulation of phosphate in the medium, and 32P-labeled hypophosphite was incorporated into the cell as organic phosphate. When phosphate was present in the medium, the isolate failed to metabolize phosphite. In the presence of phosphite and hypophosphite, the isolate first utilized phosphite and then hypophosphite."}
{"id": "PMID:26318", "title": "Factors influencing intraoperative gastric regurgitation: a prospective random study of nasogastric tube drainage.", "content": "A prospective study was conducted to determine the incidence of \"silent\" gastric regurgitation and aspiration during general anesthesia in 146 patients randomized with respect to presence of a nasogastric tube. A bland dye was instilled in the stomach to serve as the determinant marker. The overall incidence of regugitation was 8.9% and of aspiration, 2.1% in spite of the uniform use of an endotracheal tube. The incidence of regurgitation was twice as high when anesthesia was given by an inexperienced anesthetist (11% vs 5.6%) and in patients without nasogastric tubes (12% vs 6%), although such differences were not statistically significant. The primary agent used, difficulty of endotracheal intubation, location of surgical incision, and duration of anesthesia did not alter the incidence of regurgitation or aspiration. No correlation was found between the detection of subclinical aspiration and the development of postoperative pulmonary complications.", "contents": "Factors influencing intraoperative gastric regurgitation: a prospective random study of nasogastric tube drainage. A prospective study was conducted to determine the incidence of \"silent\" gastric regurgitation and aspiration during general anesthesia in 146 patients randomized with respect to presence of a nasogastric tube. A bland dye was instilled in the stomach to serve as the determinant marker. The overall incidence of regugitation was 8.9% and of aspiration, 2.1% in spite of the uniform use of an endotracheal tube. The incidence of regurgitation was twice as high when anesthesia was given by an inexperienced anesthetist (11% vs 5.6%) and in patients without nasogastric tubes (12% vs 6%), although such differences were not statistically significant. The primary agent used, difficulty of endotracheal intubation, location of surgical incision, and duration of anesthesia did not alter the incidence of regurgitation or aspiration. No correlation was found between the detection of subclinical aspiration and the development of postoperative pulmonary complications."}
{"id": "PMID:26319", "title": "[2-Br-2-ethyl-4-hydroxybutyramide and 2-Br-2-ethyl-4-butyrolactam as carbromal metabolites (author's transl)].", "content": "2-Brom-2-ethyl-4-hydroxybutyramide and 2-Brom-2-ethyl-4-butyrolactam have been isolated from the urine of patients with carbromal intoxications as well as from the urine of rat, mouse and dog after the application of either carbromal or bromdiethylacetamide and identified by means of mass-, NMR- and IR spectroscopy.", "contents": "[2-Br-2-ethyl-4-hydroxybutyramide and 2-Br-2-ethyl-4-butyrolactam as carbromal metabolites (author's transl)]. 2-Brom-2-ethyl-4-hydroxybutyramide and 2-Brom-2-ethyl-4-butyrolactam have been isolated from the urine of patients with carbromal intoxications as well as from the urine of rat, mouse and dog after the application of either carbromal or bromdiethylacetamide and identified by means of mass-, NMR- and IR spectroscopy."}
{"id": "PMID:26320", "title": "[Cardiotoxicity of bromethylbutyramide (carbromide) (author's transl)].", "content": "Bromethylbutyramide (Carbromide), a quantitatively important metabolite of carbromal, diminished the contractility of electrically driven and the frequency of spontaneously beating guinea-pig atria. The negative inotropic action of bromethylbutyramide occurred at concentrations which are reached in human carbromal poisoning. The cardiodepressive actions of bromethylbutyramide and carbromal may be important for the course and the ending of severe carbromal intoxications.", "contents": "[Cardiotoxicity of bromethylbutyramide (carbromide) (author's transl)]. Bromethylbutyramide (Carbromide), a quantitatively important metabolite of carbromal, diminished the contractility of electrically driven and the frequency of spontaneously beating guinea-pig atria. The negative inotropic action of bromethylbutyramide occurred at concentrations which are reached in human carbromal poisoning. The cardiodepressive actions of bromethylbutyramide and carbromal may be important for the course and the ending of severe carbromal intoxications."}
{"id": "PMID:26322", "title": "[Re-evaluation of barbexaclone in 20 epileptic patients].", "content": "The clinically observed results in 20 patients treated with barbexaclone for a period of 2 1/2 years are reported. Therapeutic efficiency as well as side effects are discussed. The authors draw attention to the fact that there was a concomitant improvement in the behaviour of some patients and a diminution of maintainence dosage in relation to a previously published trial.", "contents": "[Re-evaluation of barbexaclone in 20 epileptic patients]. The clinically observed results in 20 patients treated with barbexaclone for a period of 2 1/2 years are reported. Therapeutic efficiency as well as side effects are discussed. The authors draw attention to the fact that there was a concomitant improvement in the behaviour of some patients and a diminution of maintainence dosage in relation to a previously published trial."}
{"id": "PMID:26326", "title": "Effect of orthophosphate and oxalate on the cold-induced release of calcium from sarcoplasmic reticulum preparations from rabbit skeletal muscle.", "content": "The cold-induced release of calcium from sarcoplasmic reticulum preparations from both white and red muscles of the rabbit was studied. Part of the release was due to the increase in pH of the reaction mixture with cooling. Calcium release was greatly reduced or completely prevented by the inclusion of oxalate or inorganic orthophosphate in the medium. No release occurred in 5 mM oxalate. With phosphate, the proportion of the calcium previously taken up at 23 degrees C that was released at 0 degrees C became progressively smaller as the phosphate concentration was increased. When the pH was adjusted to be the same at 0 degrees C as at 23 degrees C there was little release from white muscle preparations in 10 mM phosphate and no release when the phosphate concentration was 20 mM or more. With red muscle preparations calcium was released at higher phosphate concentrations, 8% of the amount previously taken up still being released at 50 mM phosphate and a smaller amount at 100 mM phosphate. The effects of oxalate and phosphate can be explained in terms of the reduction in free calcium concentration inside the vesicles by calcium precipitants, and a difference in the temperature coefficients of calcium inflow and outflow.", "contents": "Effect of orthophosphate and oxalate on the cold-induced release of calcium from sarcoplasmic reticulum preparations from rabbit skeletal muscle. The cold-induced release of calcium from sarcoplasmic reticulum preparations from both white and red muscles of the rabbit was studied. Part of the release was due to the increase in pH of the reaction mixture with cooling. Calcium release was greatly reduced or completely prevented by the inclusion of oxalate or inorganic orthophosphate in the medium. No release occurred in 5 mM oxalate. With phosphate, the proportion of the calcium previously taken up at 23 degrees C that was released at 0 degrees C became progressively smaller as the phosphate concentration was increased. When the pH was adjusted to be the same at 0 degrees C as at 23 degrees C there was little release from white muscle preparations in 10 mM phosphate and no release when the phosphate concentration was 20 mM or more. With red muscle preparations calcium was released at higher phosphate concentrations, 8% of the amount previously taken up still being released at 50 mM phosphate and a smaller amount at 100 mM phosphate. The effects of oxalate and phosphate can be explained in terms of the reduction in free calcium concentration inside the vesicles by calcium precipitants, and a difference in the temperature coefficients of calcium inflow and outflow."}
{"id": "PMID:26327", "title": "Purification and properties of the pyrrolidonecarboxylate peptidase of Streptococcus faecium.", "content": "Pyrrolidonecarboxylate peptidase (EC 3.4.11.8) from Streptococcus faecium was purified by fractionation with streptomycin sulphate and ammonium sulphate, by chromatography on Sephadex G200 and DEAE-cellulose, and by preparative electrophoresis on Sephadex G25. The purified enzyme on acrylamide gel showed a strong protein band which contained enzyme activity and a very faint band which had no activity.  The subunit molecular weight of the purified enzyme was estimated by acrylamide gel electrophoresis in sodium dodecyl sulphate to be 42,000 +/- 1,000. The enzyme showed optimum activity at pH 7.6 and was unstable in the absence of 2-mercaptoethanol. The sensitivity of the enzyme to alkylating agents (N-ethylmaleimide and iodoacetamide) suggested that free sulphydryl groups were essential for enzyme activity. The enzyme was rapidly inactivated above 45 degrees C. The values of the Michaelis constants (Km) obtained with various L-pyrrolidonecarboxylyl dipeptides were similar although there was a 10-fold range in the maximal rates of hydrolysis of these substrates. Inhibition studies showed that the substrate analogues 2-pyrrolidone and pyrrolidonecarboxylate are competitive inhibitors of the enzyme. The binding of substrates and inhibitors to the active site of the enzyme is discussed.", "contents": "Purification and properties of the pyrrolidonecarboxylate peptidase of Streptococcus faecium. Pyrrolidonecarboxylate peptidase (EC 3.4.11.8) from Streptococcus faecium was purified by fractionation with streptomycin sulphate and ammonium sulphate, by chromatography on Sephadex G200 and DEAE-cellulose, and by preparative electrophoresis on Sephadex G25. The purified enzyme on acrylamide gel showed a strong protein band which contained enzyme activity and a very faint band which had no activity.  The subunit molecular weight of the purified enzyme was estimated by acrylamide gel electrophoresis in sodium dodecyl sulphate to be 42,000 +/- 1,000. The enzyme showed optimum activity at pH 7.6 and was unstable in the absence of 2-mercaptoethanol. The sensitivity of the enzyme to alkylating agents (N-ethylmaleimide and iodoacetamide) suggested that free sulphydryl groups were essential for enzyme activity. The enzyme was rapidly inactivated above 45 degrees C. The values of the Michaelis constants (Km) obtained with various L-pyrrolidonecarboxylyl dipeptides were similar although there was a 10-fold range in the maximal rates of hydrolysis of these substrates. Inhibition studies showed that the substrate analogues 2-pyrrolidone and pyrrolidonecarboxylate are competitive inhibitors of the enzyme. The binding of substrates and inhibitors to the active site of the enzyme is discussed."}
{"id": "PMID:26328", "title": "Congenital and developmental anomalies of the genitalia of slaughtered bulls.", "content": "The genital tracts of 968 slaughtered bulls (46% of which were young post-puberal animals) were examined for defects of a congenital or developmental nature. The overall occurrence of such lesions was 7%. These comprised persistent penile frenulum (0.5%), hypospadias (0.3%), detached urethral process (0.4%), testicular hypoplasia (0.2%), cryptorchidism (0.6%), mesonephric duct abnormalities (1.1%) and bulbourethral cysts, fusion and aplasia (3.6%). Segmental aplasia of the mesonephric duct, not previously recorded in the study area, was found in 4 Shorthorn bulls (0.4%); 2 affected animals were from one herd. In 3 cases of hypospadias (2 from one herd), the urethra communicated with the ventral surface of the penis at the junction of the body and glans through a slit-like orifice. The occurrence of defects observed was generally comparable to that found in bull populations elsewhere but elevated occurrence of several defects in particular herds emphasized the need for further study.", "contents": "Congenital and developmental anomalies of the genitalia of slaughtered bulls. The genital tracts of 968 slaughtered bulls (46% of which were young post-puberal animals) were examined for defects of a congenital or developmental nature. The overall occurrence of such lesions was 7%. These comprised persistent penile frenulum (0.5%), hypospadias (0.3%), detached urethral process (0.4%), testicular hypoplasia (0.2%), cryptorchidism (0.6%), mesonephric duct abnormalities (1.1%) and bulbourethral cysts, fusion and aplasia (3.6%). Segmental aplasia of the mesonephric duct, not previously recorded in the study area, was found in 4 Shorthorn bulls (0.4%); 2 affected animals were from one herd. In 3 cases of hypospadias (2 from one herd), the urethra communicated with the ventral surface of the penis at the junction of the body and glans through a slit-like orifice. The occurrence of defects observed was generally comparable to that found in bull populations elsewhere but elevated occurrence of several defects in particular herds emphasized the need for further study."}
{"id": "PMID:26332", "title": "Biochemical aspects of cardiac muscle differentiation.", "content": "Experiments were designed to determine whether DNA synthesis ceases in terminally differentiating cardiac muscle of the rat because the activity of the putative replicative DNA polymerase (DNA polymerase alpha) is lost or whether the activity of this enzyme is lost because DNA synthesis ceases. DNA-template availability and 3'-hydroxyl termini in nuclei and chromatin, isolated from cardiac muscle at various times during the developmental period in which DNA synthesis and the activity of DNA polymerase alpha are decreasing, were measured by using Escherichia coli DNA polymerase I, Micrococcus luteus DNA polymerase and DNA polymerase alpha under optimal conditions. Density-shift experiments with bromodeoxyuridine triphosphate and isopycnic analysis indicate that DNA chains being replicated semi-conservatively in vivo continue to be elongated in isolated nuclei by exogenous DNA polymerases. DNA template and 3'-hydroxyl termini available to exogenously added DNA polymerases do not change as cardiac muscle differentiates and the rate of DNA synthesis decreases and ceases in vivo. Template availability and 3'-hydroxyl termini are also not changed in nuclei isolated from cardiac muscle in which DNA synthesis had been inhibited by administration of isoproterenol and theophylline to newborn rats. DNA-template availability and 3'-hydroxyl termini, however, were substantially increased in nuclei and chromatin from cardiac muscle of adult rats. This increase is not due to elevated deoxyribonuclease activity in nuclei and chromatin of the adult. Electron microscopy indicates that this increase is also not due to dispersal of the chromatin or disruption of nuclear morphology. Density-shift experiments and isopycnic analysis of DNA from cardiac muscle of the adult show that it is more fragmented than DNA from cardiac-muscle cells that are, or have recently ceased, dividing. These studies indicate that DNA synthesis ceases in terminally differentiating cardiac muscle because the activity of a replicative DNA polymerase is lost, rather than the activity of this enzyme being lost because DNA synthesis ceases.", "contents": "Biochemical aspects of cardiac muscle differentiation. Experiments were designed to determine whether DNA synthesis ceases in terminally differentiating cardiac muscle of the rat because the activity of the putative replicative DNA polymerase (DNA polymerase alpha) is lost or whether the activity of this enzyme is lost because DNA synthesis ceases. DNA-template availability and 3'-hydroxyl termini in nuclei and chromatin, isolated from cardiac muscle at various times during the developmental period in which DNA synthesis and the activity of DNA polymerase alpha are decreasing, were measured by using Escherichia coli DNA polymerase I, Micrococcus luteus DNA polymerase and DNA polymerase alpha under optimal conditions. Density-shift experiments with bromodeoxyuridine triphosphate and isopycnic analysis indicate that DNA chains being replicated semi-conservatively in vivo continue to be elongated in isolated nuclei by exogenous DNA polymerases. DNA template and 3'-hydroxyl termini available to exogenously added DNA polymerases do not change as cardiac muscle differentiates and the rate of DNA synthesis decreases and ceases in vivo. Template availability and 3'-hydroxyl termini are also not changed in nuclei isolated from cardiac muscle in which DNA synthesis had been inhibited by administration of isoproterenol and theophylline to newborn rats. DNA-template availability and 3'-hydroxyl termini, however, were substantially increased in nuclei and chromatin from cardiac muscle of adult rats. This increase is not due to elevated deoxyribonuclease activity in nuclei and chromatin of the adult. Electron microscopy indicates that this increase is also not due to dispersal of the chromatin or disruption of nuclear morphology. Density-shift experiments and isopycnic analysis of DNA from cardiac muscle of the adult show that it is more fragmented than DNA from cardiac-muscle cells that are, or have recently ceased, dividing. These studies indicate that DNA synthesis ceases in terminally differentiating cardiac muscle because the activity of a replicative DNA polymerase is lost, rather than the activity of this enzyme being lost because DNA synthesis ceases."}
{"id": "PMID:26329", "title": "On the mode of action of antianginal drugs.", "content": "The antianginal action of coronary dilating drugs seems to be related at least partly to their effect of improving the blood supply of the ischemic myocardium. No correlation was found between coronary dilating action of these drugs in the normal myocardium and in the ischemic area, however. It has been shown that coronary dilator drugs are able to produce a further dilatation of the vascular bed which is already in maximum hypoxic dilatation. The antianginal effect of adrenergic beta receptor blockade cannot be explained solely by its negative chronotropic and inotropic action. It involves a favourable redistribution of the coronary flow which is increased in the ischemic area. In addition, there is evidence for a direct cardiac metabolic effect of beta blockade which reduces the myocardial oxygen requirement and moderates the ischemic diminution of the myocardial lactate uptake independently of its action on the autonomic nervous control and other extracardiac factors as well as on contractility, heart rate and myocardial blood supply.", "contents": "On the mode of action of antianginal drugs. The antianginal action of coronary dilating drugs seems to be related at least partly to their effect of improving the blood supply of the ischemic myocardium. No correlation was found between coronary dilating action of these drugs in the normal myocardium and in the ischemic area, however. It has been shown that coronary dilator drugs are able to produce a further dilatation of the vascular bed which is already in maximum hypoxic dilatation. The antianginal effect of adrenergic beta receptor blockade cannot be explained solely by its negative chronotropic and inotropic action. It involves a favourable redistribution of the coronary flow which is increased in the ischemic area. In addition, there is evidence for a direct cardiac metabolic effect of beta blockade which reduces the myocardial oxygen requirement and moderates the ischemic diminution of the myocardial lactate uptake independently of its action on the autonomic nervous control and other extracardiac factors as well as on contractility, heart rate and myocardial blood supply."}
{"id": "PMID:26333", "title": "Deacylation of acetyl-coenzyme A and acetylcarnitine by liver preparations.", "content": "The breakdown of acetylcarnitine catalysed by extracts of rat and sheep liver was completely abolished by Sephadex G-25 gel filtration, whereas the hydrolysis of acetyl-CoA was unaffected. Acetyl-CoA and CoA acted catalytically in restoring the ability of Sephadex-treated extracts to break down acetylcarnitine, which was therefore not due to an acetylcarnitine hydrolase but to the sequential action of carnitine acetyltransferase and acetyl-CoA hydrolase. Some 75% of the acetyl-CoA hydrolase activity of sheep liver was localized in the mitochondrial fraction. Two distinct acetyl-CoA hydrolases were partially purified from extracts of sheep liver mitochondria. Both enzymes hydrolysed other short-chain acyl-CoA compounds and succinyl-CoA (3-carboxypropionyl-CoA), but with one acetyl-CoA was the preferred substrate.", "contents": "Deacylation of acetyl-coenzyme A and acetylcarnitine by liver preparations. The breakdown of acetylcarnitine catalysed by extracts of rat and sheep liver was completely abolished by Sephadex G-25 gel filtration, whereas the hydrolysis of acetyl-CoA was unaffected. Acetyl-CoA and CoA acted catalytically in restoring the ability of Sephadex-treated extracts to break down acetylcarnitine, which was therefore not due to an acetylcarnitine hydrolase but to the sequential action of carnitine acetyltransferase and acetyl-CoA hydrolase. Some 75% of the acetyl-CoA hydrolase activity of sheep liver was localized in the mitochondrial fraction. Two distinct acetyl-CoA hydrolases were partially purified from extracts of sheep liver mitochondria. Both enzymes hydrolysed other short-chain acyl-CoA compounds and succinyl-CoA (3-carboxypropionyl-CoA), but with one acetyl-CoA was the preferred substrate."}
{"id": "PMID:26334", "title": "Ultraviolet difference-spectroscopic studies of substrate and inhibitor binding to Lactobacillus casei dihydrofolate reductase.", "content": "The u.v. difference spectra generated when methotrexate, trimethoprim or folate bind to Lactobacillus casei dihydrofolate reductase were analysed. The difference spectrum producted by methotrexate binding is shown to consist of three components: (a) one closely resembling that observed on protonation of methotrexate, reflecting an increased degree of protonation on binding; (b) a pH-independent contribution corresponding to a 40 nm shift to longer wavelengths of a single absorption band of methotrexate: (c) a component arising from perturbation of tryptophan residue(s) of the enzyme. Quantitative analysis of the pH-dependence of component (a) shows that pK of methotrexate is increased from 5.35 to 8.55 (+/-0.10) on binding. In contrast, folate is not protonated when bound to the enzyme at neutral pH. At pH7.5, where methotrexate is bound 2000 times more tightly than folate, one-third of the difference in binding energy between the two compounds arises from the difference in chaarge stage. A similar analysis of the difference spectra generated on trimethoprim binding demonstrates that this compound, too, shows an increase in pK on binding but only from 7.22 to 7.90 (+/-0.10), suggesting that its 2,4-diaminopyrimidine ring does not bind to the enzyme in precisely the same way as the corresponding moiety of methotrexate.", "contents": "Ultraviolet difference-spectroscopic studies of substrate and inhibitor binding to Lactobacillus casei dihydrofolate reductase. The u.v. difference spectra generated when methotrexate, trimethoprim or folate bind to Lactobacillus casei dihydrofolate reductase were analysed. The difference spectrum producted by methotrexate binding is shown to consist of three components: (a) one closely resembling that observed on protonation of methotrexate, reflecting an increased degree of protonation on binding; (b) a pH-independent contribution corresponding to a 40 nm shift to longer wavelengths of a single absorption band of methotrexate: (c) a component arising from perturbation of tryptophan residue(s) of the enzyme. Quantitative analysis of the pH-dependence of component (a) shows that pK of methotrexate is increased from 5.35 to 8.55 (+/-0.10) on binding. In contrast, folate is not protonated when bound to the enzyme at neutral pH. At pH7.5, where methotrexate is bound 2000 times more tightly than folate, one-third of the difference in binding energy between the two compounds arises from the difference in chaarge stage. A similar analysis of the difference spectra generated on trimethoprim binding demonstrates that this compound, too, shows an increase in pK on binding but only from 7.22 to 7.90 (+/-0.10), suggesting that its 2,4-diaminopyrimidine ring does not bind to the enzyme in precisely the same way as the corresponding moiety of methotrexate."}
{"id": "PMID:26335", "title": "Characterization of the papain active centre by using two-protonic-state electrophiles as reactivity probes. Evidence for nucleophilic reactivity in the un-interrupted cysteine-25-histidine-159 interactive system.", "content": "1.2,2'-Dipyridyl disulphide (2-Py-S-S-2-Py) and n-propyl 2-pyridyl disulphide (propyl-S-S-2-Py) were used as two-protonic-state reactivity probes to investigate the active centre of papain (EC 3.4.22.2).2. The existence of a striking rate optimum at pH approx. 4 in the reaction of papain not only with the symmetrical probe but also with the unsymmetrical probe is shown to constitute compelling evidence that the thiolate ion component of the cysteine-25-histidine-159 interactive system of papain possesses appreciable nucleophilic character. It is not a necessary requirement that the probe reagent should engage the imidazolium ion of histidine-159 in hydrogen-bonding for the sulphur atom of the interactive system to display nucleophilic character. The single proton-binding site of propyl-S-S-2-Py cannot simultaneously interrupt the active-centre ion pair and provide for rate enhancement as the pH is lowered towards 4. The possible implication of this for the mechanism of papain-catalysed hydrolysis is discussed. 3. The suspected difference in the active centres of papain and ficin (EC 3.4.22.3), which could be a lack in ficin of a carboxy group conformationally equivalent to that of aspartic acid-158 of papain is confirmed. The reactivity of the papain thiol group towards both probe reagents is controlled by two ionizations with pKa close to 4 that are positively co-operative. 4. In the reaction of papain with 2-Py-S-S-2-Py. the reactivity appears to be controlled also by an addition ionization with pKa approx. 5. Possible origins of this additional ionization are discussed. K. The spectral and ionization characteristics of propyl-S-S-2-Py are reported. 6. The reagent reacts rapidly with thiol groups at the sulphur atom distal from the pyridyl ring to provide, at pH values below 9, stoicheiometric release of 2-thiopyridone. This property, together with the ability of the reagent markedly to increase its electrophilicity consequent on protonation, suggests alkyl-2-pyridyl disulphides in general as valuable two-protonic-state reactivity probes with exceptional specificity for thiol groups.", "contents": "Characterization of the papain active centre by using two-protonic-state electrophiles as reactivity probes. Evidence for nucleophilic reactivity in the un-interrupted cysteine-25-histidine-159 interactive system. 1.2,2'-Dipyridyl disulphide (2-Py-S-S-2-Py) and n-propyl 2-pyridyl disulphide (propyl-S-S-2-Py) were used as two-protonic-state reactivity probes to investigate the active centre of papain (EC 3.4.22.2).2. The existence of a striking rate optimum at pH approx. 4 in the reaction of papain not only with the symmetrical probe but also with the unsymmetrical probe is shown to constitute compelling evidence that the thiolate ion component of the cysteine-25-histidine-159 interactive system of papain possesses appreciable nucleophilic character. It is not a necessary requirement that the probe reagent should engage the imidazolium ion of histidine-159 in hydrogen-bonding for the sulphur atom of the interactive system to display nucleophilic character. The single proton-binding site of propyl-S-S-2-Py cannot simultaneously interrupt the active-centre ion pair and provide for rate enhancement as the pH is lowered towards 4. The possible implication of this for the mechanism of papain-catalysed hydrolysis is discussed. 3. The suspected difference in the active centres of papain and ficin (EC 3.4.22.3), which could be a lack in ficin of a carboxy group conformationally equivalent to that of aspartic acid-158 of papain is confirmed. The reactivity of the papain thiol group towards both probe reagents is controlled by two ionizations with pKa close to 4 that are positively co-operative. 4. In the reaction of papain with 2-Py-S-S-2-Py. the reactivity appears to be controlled also by an addition ionization with pKa approx. 5. Possible origins of this additional ionization are discussed. K. The spectral and ionization characteristics of propyl-S-S-2-Py are reported. 6. The reagent reacts rapidly with thiol groups at the sulphur atom distal from the pyridyl ring to provide, at pH values below 9, stoicheiometric release of 2-thiopyridone. This property, together with the ability of the reagent markedly to increase its electrophilicity consequent on protonation, suggests alkyl-2-pyridyl disulphides in general as valuable two-protonic-state reactivity probes with exceptional specificity for thiol groups."}
{"id": "PMID:26336", "title": "Purification of plasminogen activators from human seminal plasma.", "content": "Two plasminogen activators (1 and 2) were isolated from human seminal plasma by hiigh-speed centrifugation, Sephadex-gel filtration and ion-exchange chromatography. The activators were shown to be homogeneous by polyacrylamide-disc -gel electrophoresis at pH 8.3 and 4.5, and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The molecular weights of activators 1 and 2 were estimated as 69 000 and 74 000. Their amino acid compositions are very similar, both being high in aspartic acid, glutamic acid, serine, glycine and leucine, and low in methionine, tryptophan, tyrosine, isoleucine and histidine. Activators 1 and 2 each possess 16 cysteine residues. Both activators have isoelectric points of approx. 7.0, are stable over a wide pH range at temperatures up to 60 degrees C, but lose activity at higher temperatures, particularly under very basic or acidic conditions. They are not inhibited by EDTA, Mg2+ and Ca2+ at 10 mM concentrations, but their activity decreases on addition of 10 mM-cysteine or Fe2+ and 6-aminohexanoate or sera from pregnant women. The precipitin band formed between urokinase and its antiserum is continuous with the precipitin bands formed between the seminal plasminogen activators and the urokinase antiserum. Antisera to urokinase inhibit both the activity of urokinase and the seminal plasminogen activators.", "contents": "Purification of plasminogen activators from human seminal plasma. Two plasminogen activators (1 and 2) were isolated from human seminal plasma by hiigh-speed centrifugation, Sephadex-gel filtration and ion-exchange chromatography. The activators were shown to be homogeneous by polyacrylamide-disc -gel electrophoresis at pH 8.3 and 4.5, and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The molecular weights of activators 1 and 2 were estimated as 69 000 and 74 000. Their amino acid compositions are very similar, both being high in aspartic acid, glutamic acid, serine, glycine and leucine, and low in methionine, tryptophan, tyrosine, isoleucine and histidine. Activators 1 and 2 each possess 16 cysteine residues. Both activators have isoelectric points of approx. 7.0, are stable over a wide pH range at temperatures up to 60 degrees C, but lose activity at higher temperatures, particularly under very basic or acidic conditions. They are not inhibited by EDTA, Mg2+ and Ca2+ at 10 mM concentrations, but their activity decreases on addition of 10 mM-cysteine or Fe2+ and 6-aminohexanoate or sera from pregnant women. The precipitin band formed between urokinase and its antiserum is continuous with the precipitin bands formed between the seminal plasminogen activators and the urokinase antiserum. Antisera to urokinase inhibit both the activity of urokinase and the seminal plasminogen activators."}
{"id": "PMID:26337", "title": "Studies of an acid-induced species of purple membrane from Halobacterium halobium.", "content": "A new spectral species of the purple membrane of Halobacterium halobium has been observed below pH 3.2. The formation of this new species is temperature-dependent and is favoured by increasing temperature up to the physiological range of the organism. The rate of formation at pH 3.0 and 22 degrees C is 7.9 x 10-3s-1. The spectral distribution and temperature-dependence of the new species suggest that it may be phototransiet O, stabilized by low pH. Flash-photolytic experiments in the pH range 7.2-2.7 show a pH-dependence corresponding to the static events and are consistent with a single protonation of bacteriorhodopsin below pH 3.22. These results can also be interpreted in terms of the stabilization of phototransient O at low pH. The temperature-dependence of the formation of the acid-induced species may reflect a relationship with the phase transition of the membrane.", "contents": "Studies of an acid-induced species of purple membrane from Halobacterium halobium. A new spectral species of the purple membrane of Halobacterium halobium has been observed below pH 3.2. The formation of this new species is temperature-dependent and is favoured by increasing temperature up to the physiological range of the organism. The rate of formation at pH 3.0 and 22 degrees C is 7.9 x 10-3s-1. The spectral distribution and temperature-dependence of the new species suggest that it may be phototransiet O, stabilized by low pH. Flash-photolytic experiments in the pH range 7.2-2.7 show a pH-dependence corresponding to the static events and are consistent with a single protonation of bacteriorhodopsin below pH 3.22. These results can also be interpreted in terms of the stabilization of phototransient O at low pH. The temperature-dependence of the formation of the acid-induced species may reflect a relationship with the phase transition of the membrane."}
{"id": "PMID:26338", "title": "Evidence for a proton/sugar symport in the yeast Rhodotorula gracilis (glutinis).", "content": "1. The uptake of monosaccharides and polyols in the obligatory aerobic yeast Rhodotorula gracilis (glutinis) was accompanied by proton uptake. 2. The half-saturation constant of transport, KT, depended on pH, changing from about 2mM at pH 4.5 to 80mM at pH8.5 for D-xylose; this change of the effective carrier affinity was reversible. 3. The apparent dissociation constant of the monosaccharide carrier was estimated at pKa 6.75. 4. At pH8.5, when the pH gradient across the cell membrane vanished, no sugar accumulation was demonstrable. 5. The half-saturation constants of sugar uptake and H+ co-transport were very similar to each other, the latter obviously being controlled by the former. 6. The H+/sugar stoicheiometry remained constant under various physiological conditions; it amounted to one H+ ion per sugar molecule taken up. 7. The data are interpreted as a strong piece of evidence in favour of the active monosaccharide transport in R. gracilis (glutinis) being an H+-symport energized by the electrochemical gradient of H+ across the plasma membrane of the yeast.", "contents": "Evidence for a proton/sugar symport in the yeast Rhodotorula gracilis (glutinis). 1. The uptake of monosaccharides and polyols in the obligatory aerobic yeast Rhodotorula gracilis (glutinis) was accompanied by proton uptake. 2. The half-saturation constant of transport, KT, depended on pH, changing from about 2mM at pH 4.5 to 80mM at pH8.5 for D-xylose; this change of the effective carrier affinity was reversible. 3. The apparent dissociation constant of the monosaccharide carrier was estimated at pKa 6.75. 4. At pH8.5, when the pH gradient across the cell membrane vanished, no sugar accumulation was demonstrable. 5. The half-saturation constants of sugar uptake and H+ co-transport were very similar to each other, the latter obviously being controlled by the former. 6. The H+/sugar stoicheiometry remained constant under various physiological conditions; it amounted to one H+ ion per sugar molecule taken up. 7. The data are interpreted as a strong piece of evidence in favour of the active monosaccharide transport in R. gracilis (glutinis) being an H+-symport energized by the electrochemical gradient of H+ across the plasma membrane of the yeast."}
{"id": "PMID:26339", "title": "Purification and properties of a manganese-stimulated deoxyribonuclease produced during sporulation of Bacillus subtilis.", "content": "A DNAase (deoxyribonuclease) was isolated from culture supernatants of sporulating Bacillus subtilis 168. The purified enzyme migrated as a single band during polyacrylamide-gel electrophoresis. The enzyme differs from other DNAases of B. subtilis in molecular weight, metal-ion requirement and mode of action. The enzyme was inactive in the absence of metal ions, and exhibited optimum activity with 10 mM-Mn2+, although Mg2+, Cd2+ and Co2+ could also permit some activity. The pH optimum for the enzyme was pH 7.5, and it degraded linear-duplex DNA or closed-circular-duplex DNA to acid-soluble material. There was little or no activity on single-stranded DNA or rRNA. Sucrose-gradient analysis of the products of DNAase action on bacteriophage T7 DNA showed that endonucleolytic cleavage had occurred by the introduction of single-strand breaks in both strands of the duplex. The molecular weight of the enzyme was determined, by gel filtration on Sephadex G-75, to be 12000.", "contents": "Purification and properties of a manganese-stimulated deoxyribonuclease produced during sporulation of Bacillus subtilis. A DNAase (deoxyribonuclease) was isolated from culture supernatants of sporulating Bacillus subtilis 168. The purified enzyme migrated as a single band during polyacrylamide-gel electrophoresis. The enzyme differs from other DNAases of B. subtilis in molecular weight, metal-ion requirement and mode of action. The enzyme was inactive in the absence of metal ions, and exhibited optimum activity with 10 mM-Mn2+, although Mg2+, Cd2+ and Co2+ could also permit some activity. The pH optimum for the enzyme was pH 7.5, and it degraded linear-duplex DNA or closed-circular-duplex DNA to acid-soluble material. There was little or no activity on single-stranded DNA or rRNA. Sucrose-gradient analysis of the products of DNAase action on bacteriophage T7 DNA showed that endonucleolytic cleavage had occurred by the introduction of single-strand breaks in both strands of the duplex. The molecular weight of the enzyme was determined, by gel filtration on Sephadex G-75, to be 12000."}
{"id": "PMID:26340", "title": "Collagenolytic cathepsin activity in rabbit peritoneal polymorphonuclear leucocyte granules.", "content": "Collagenolytic cathepsin activity was detected in lysed rabbit peritoneal polymorphonuclear leucocytes. The pH optimum was around 3, and activity was greatly enhanced by the presence of cysteine and EDTA. Digestion of polymeric collagen resulted in the release of alpha, beta, and gamma-chains. Collagenolytic cathepsin activity was associated mainly with the granule fraction isolated from homogenates by differential centrifugation. The granule fraction was further fractionated by isopycnic density-gradient centrifugation, and the collagenolytic cathepsin activity was shown to be associated with the azurophil and tertiary granules, both lysosome-like organelles.", "contents": "Collagenolytic cathepsin activity in rabbit peritoneal polymorphonuclear leucocyte granules. Collagenolytic cathepsin activity was detected in lysed rabbit peritoneal polymorphonuclear leucocytes. The pH optimum was around 3, and activity was greatly enhanced by the presence of cysteine and EDTA. Digestion of polymeric collagen resulted in the release of alpha, beta, and gamma-chains. Collagenolytic cathepsin activity was associated mainly with the granule fraction isolated from homogenates by differential centrifugation. The granule fraction was further fractionated by isopycnic density-gradient centrifugation, and the collagenolytic cathepsin activity was shown to be associated with the azurophil and tertiary granules, both lysosome-like organelles."}
{"id": "PMID:26358", "title": "Inorganic pyrophosphatase activity of the synovial fluid. Kinetic and clinical study.", "content": "Inorganic pyrophosphatase activity has been partially characterized in joint fluid and determined in patients with sporadic and familial chondrocalcinosis and their controls. Optimal pH was established at 3.5 and Km values were estimated. Ca-2 and Mg-2 did not affect this activity whereas orthophosphate (Pi) strongly inhibited it. In the clinical study no significant differences were found among groups. This suggests that if a pyrophosphatase defect is present it might be localized in joint tissue and not be reflected in synovial fluid.", "contents": "Inorganic pyrophosphatase activity of the synovial fluid. Kinetic and clinical study. Inorganic pyrophosphatase activity has been partially characterized in joint fluid and determined in patients with sporadic and familial chondrocalcinosis and their controls. Optimal pH was established at 3.5 and Km values were estimated. Ca-2 and Mg-2 did not affect this activity whereas orthophosphate (Pi) strongly inhibited it. In the clinical study no significant differences were found among groups. This suggests that if a pyrophosphatase defect is present it might be localized in joint tissue and not be reflected in synovial fluid."}
{"id": "PMID:26359", "title": "The psychopharmacological properties of pinazepam, a new benzodiazepine derivative.", "content": "The pharmacological differences between the behavioural effects of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) and diazepam were investigated in rats. Pinazepam was more than twice as active as diazepam at a dose range between 1.25--10 mg/kg in reducing the conditioned emotional response (CER). Only at doses of 2.5 and 5 mg/kg prevented pinazepam the disruption of the avoidance responses induced by inverting the conditioned stimulus (CS). On the other hand pinazepam was less active than diazepam in reducing the number of avoidance responses in a conditioned avoidance situation. Neither pinazepam nor diazepam disrupted the conditioned responses in a fixed-interval operant behaviour.", "contents": "The psychopharmacological properties of pinazepam, a new benzodiazepine derivative. The pharmacological differences between the behavioural effects of 7-chloro-1-propargyl-5-phenyl-3H-1,4-benzodiazepin-2-one (pinazepam) and diazepam were investigated in rats. Pinazepam was more than twice as active as diazepam at a dose range between 1.25--10 mg/kg in reducing the conditioned emotional response (CER). Only at doses of 2.5 and 5 mg/kg prevented pinazepam the disruption of the avoidance responses induced by inverting the conditioned stimulus (CS). On the other hand pinazepam was less active than diazepam in reducing the number of avoidance responses in a conditioned avoidance situation. Neither pinazepam nor diazepam disrupted the conditioned responses in a fixed-interval operant behaviour."}
{"id": "PMID:26360", "title": "[Comparative experimental studies in animals and humans on gastrointestinal blood loss following antirheumatic pharmacotherapy (author's transl)].", "content": "The gastrointestinal blood loss caused by the two antirheumatic drugs acetyl salicylic acid (ASA) and 4-acetamidophenyl-2-acetoxybenzoate (benorilate, Benortan) was compared in experimental animals and humans by measuring the total body iron retention. In Wistar rats and humans the results indicate that the daily iron loss under ASA is significantly higher (almost by the factor 2) than that under benorilate.", "contents": "[Comparative experimental studies in animals and humans on gastrointestinal blood loss following antirheumatic pharmacotherapy (author's transl)]. The gastrointestinal blood loss caused by the two antirheumatic drugs acetyl salicylic acid (ASA) and 4-acetamidophenyl-2-acetoxybenzoate (benorilate, Benortan) was compared in experimental animals and humans by measuring the total body iron retention. In Wistar rats and humans the results indicate that the daily iron loss under ASA is significantly higher (almost by the factor 2) than that under benorilate."}
{"id": "PMID:26361", "title": "A repeated dose comparison of the side effects of five antihistamines on objective assessments of psychomotor performance, central nervous system arousal and subjective appraisals of sleep and early morning behaviour.", "content": "The side effects of five antihistamines (chlorpheniramine maleate, mebhydrolin, clemastine hydrogen fumarate, Tavegil; ketotifen, and promethazine hydrochloride) were measured on subjective assessments of sleep and the integrity of early morning behaviour and objective assessments of complex psychomotor behaviour and central nervous system arousal. Fifty consenting volunteers each received one of the five preparations for a period of four days with the subjective effects being reported on a set of 10 cm line visual analogue scales and the objective assessments being made via a computer assisted reaction time task and critical flicker fusion thresholds. Chlorpheniramine, 4 mg t.d.s. for four days, produces a significant impairment in critical flicker fusion thresholds with respect to pretreatment baselines but none of the preparations showed any significant impairment in complex reaction time assessments. The subjective assessments of sleep and early morning hangover showed mebhydrolin and clemastine to be free from detrimental side effects, but promethazine and chlorpheniramine produce significant impairments in the integrity of early morning behaviour.", "contents": "A repeated dose comparison of the side effects of five antihistamines on objective assessments of psychomotor performance, central nervous system arousal and subjective appraisals of sleep and early morning behaviour. The side effects of five antihistamines (chlorpheniramine maleate, mebhydrolin, clemastine hydrogen fumarate, Tavegil; ketotifen, and promethazine hydrochloride) were measured on subjective assessments of sleep and the integrity of early morning behaviour and objective assessments of complex psychomotor behaviour and central nervous system arousal. Fifty consenting volunteers each received one of the five preparations for a period of four days with the subjective effects being reported on a set of 10 cm line visual analogue scales and the objective assessments being made via a computer assisted reaction time task and critical flicker fusion thresholds. Chlorpheniramine, 4 mg t.d.s. for four days, produces a significant impairment in critical flicker fusion thresholds with respect to pretreatment baselines but none of the preparations showed any significant impairment in complex reaction time assessments. The subjective assessments of sleep and early morning hangover showed mebhydrolin and clemastine to be free from detrimental side effects, but promethazine and chlorpheniramine produce significant impairments in the integrity of early morning behaviour."}
{"id": "PMID:26362", "title": "[Capacity of clones of vaccinia virus to multiply at different temperatures and pH values].", "content": "The study of the biological characteristics of ten clones, isolated from plaque, of vaccinia virus has made evident that two of these characteristics--the capacity to multiply at 40 degrees C and the type of CPE in animal cell cultures--can be used as genetic markers of neuropathogenicity, valued in relationship to the property to induce demyelinating encephalitis in mice injected intracerebrally or intravenously. The most neurovirulent clones demonstrated high capacity to multiply at 40 degrees C and lytic CPE; the clones, that did not have (or had at a very low level) encephalitogenic activity in mice, presented poor capacity to multiply at 40 degrees C and CPE of syncytial type. The variation of the pH of the cell culture medium enhances the difference of CPE induced by clones that had different levels of neuropathogenicity. The results are discussed in relation to their use in improving the smallpox vaccine.", "contents": "[Capacity of clones of vaccinia virus to multiply at different temperatures and pH values]. The study of the biological characteristics of ten clones, isolated from plaque, of vaccinia virus has made evident that two of these characteristics--the capacity to multiply at 40 degrees C and the type of CPE in animal cell cultures--can be used as genetic markers of neuropathogenicity, valued in relationship to the property to induce demyelinating encephalitis in mice injected intracerebrally or intravenously. The most neurovirulent clones demonstrated high capacity to multiply at 40 degrees C and lytic CPE; the clones, that did not have (or had at a very low level) encephalitogenic activity in mice, presented poor capacity to multiply at 40 degrees C and CPE of syncytial type. The variation of the pH of the cell culture medium enhances the difference of CPE induced by clones that had different levels of neuropathogenicity. The results are discussed in relation to their use in improving the smallpox vaccine."}
{"id": "PMID:26369", "title": "Comparison of speed of onset of fazadinium, pancuronium, tubocurarine and suxamethonium.", "content": "Under light general anaesthesia the speed of onset of action of fazadinium, pancuronium, tubocurarine and suxamethonium has been assessed by measuring the decrease in the twitch height of the adductor pollicis muscle following administration of the drugs. Suxamethonium produced 95% depression of the twitch height significantly faster than any of the other drugs, while the onset of fazadinium was significantly more rapid than that of the other non-depolarizing neuromuscular blocking drugs.", "contents": "Comparison of speed of onset of fazadinium, pancuronium, tubocurarine and suxamethonium. Under light general anaesthesia the speed of onset of action of fazadinium, pancuronium, tubocurarine and suxamethonium has been assessed by measuring the decrease in the twitch height of the adductor pollicis muscle following administration of the drugs. Suxamethonium produced 95% depression of the twitch height significantly faster than any of the other drugs, while the onset of fazadinium was significantly more rapid than that of the other non-depolarizing neuromuscular blocking drugs."}
{"id": "PMID:26371", "title": "A comparison of four beta-adrenoceptor antagonists in patients with asthma.", "content": "1 Cardiovascular and airways response to two non-cardioselective beta-adrenoceptor blocking drugs, propranolol and pindolol (with partial agonist activity) and two cardioselective beta-adrenoceptor blocking drugs, acebutolol (with partial agonist activity) and atenolol, were compared in twelve patients with asthma. 2 All four drugs produced a significant reduction in resting pulse rate and prevented the increase in heart rate following inhaled isoprenaline (1,500 microgram). 3 Seven patients in clinical remission showed no significant bronchoconstrictor response to any of the drugs. In the remaining five patients, bronchoconstriction was greatest following propranolol (mean reduction in FEV1 26.6%) and least following atenolol (mean reduction in FEV1 6.5%). 4 The bronchodilator response to inhaled isoprenaline was blocked by propranolol and pindolol but not by acebutolol and atenolol. 5 Partial agonist activity did not appear to be clinically useful.", "contents": "A comparison of four beta-adrenoceptor antagonists in patients with asthma. 1 Cardiovascular and airways response to two non-cardioselective beta-adrenoceptor blocking drugs, propranolol and pindolol (with partial agonist activity) and two cardioselective beta-adrenoceptor blocking drugs, acebutolol (with partial agonist activity) and atenolol, were compared in twelve patients with asthma. 2 All four drugs produced a significant reduction in resting pulse rate and prevented the increase in heart rate following inhaled isoprenaline (1,500 microgram). 3 Seven patients in clinical remission showed no significant bronchoconstrictor response to any of the drugs. In the remaining five patients, bronchoconstriction was greatest following propranolol (mean reduction in FEV1 26.6%) and least following atenolol (mean reduction in FEV1 6.5%). 4 The bronchodilator response to inhaled isoprenaline was blocked by propranolol and pindolol but not by acebutolol and atenolol. 5 Partial agonist activity did not appear to be clinically useful."}
{"id": "PMID:26372", "title": "Circulatory and alpha-adrenoceptor blocking effects of phentolamine.", "content": "1 Intravenously administered phentolamine provoked immediate decreases in diastolic blood pressure but increases in heart rate and cardiac output. 2 These immediate circulatory effects had largely disappeared twenty minutes after administration and at this time phentolamine did not inhibit increases in blood pressure which were provoked during hand immersion in ice-cold water. 3 Log dose-response curves of noradrenaline induced increases in systolic and diastolic pressure 20 min after intravenous phentolamine were shifted to the right in a parallel manner compared with the curves before phentolamine administration. 4 It was concluded that the immediate and short acting effects induced by phentolamine are due to a non-specific vasodilator effect but in addition phentolamine causes a longer acting alpha-adrenoceptor blockade at vascular adrenoceptor sites. However, by producing both pre- and post-synaptic alpha-adrenoceptor blockade this may explain why this drug exerts only a weak antihypertensive effect.", "contents": "Circulatory and alpha-adrenoceptor blocking effects of phentolamine. 1 Intravenously administered phentolamine provoked immediate decreases in diastolic blood pressure but increases in heart rate and cardiac output. 2 These immediate circulatory effects had largely disappeared twenty minutes after administration and at this time phentolamine did not inhibit increases in blood pressure which were provoked during hand immersion in ice-cold water. 3 Log dose-response curves of noradrenaline induced increases in systolic and diastolic pressure 20 min after intravenous phentolamine were shifted to the right in a parallel manner compared with the curves before phentolamine administration. 4 It was concluded that the immediate and short acting effects induced by phentolamine are due to a non-specific vasodilator effect but in addition phentolamine causes a longer acting alpha-adrenoceptor blockade at vascular adrenoceptor sites. However, by producing both pre- and post-synaptic alpha-adrenoceptor blockade this may explain why this drug exerts only a weak antihypertensive effect."}
{"id": "PMID:26370", "title": "The second Lilly Prize Lecture, University of Newcastle, July 1977. beta-Adrenergic receptor blockade in hypertension, past, present and future.", "content": "All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs have been reported which also possess alpha-adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta-adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta-adrenoceptor blocking drugs. The non-selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I-IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta-adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub-divided into groups I-IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta-adrenergic receptor blocking drugs which in addition have alpha- adrenergic receptor blocking properties (Division III).", "contents": "The second Lilly Prize Lecture, University of Newcastle, July 1977. beta-Adrenergic receptor blockade in hypertension, past, present and future. All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs have been reported which also possess alpha-adrenoceptor blocking activity. The associated properties have been used as a basis for classifying beta-adrenoceptor blocking drugs (Fitzgerald, 1969, 1972). The presence or absence of cardioselectivity is most useful for dividing beta-adrenoceptor blocking drugs. The non-selective drugs (Division I) can be further divided according to the presence or absence of intrinsic sympathomimetic activity (ISA) and membrane stabilizing activity (Fitzgerald's groups I-IV). Group I possess both membrane activity and ISA, e.g. alprenolol, oxprenolol, group II just membrane action, e.g. propanolol, group III ISA but no membrane action, e.g. pindolol. Fitzgerald placed pindolol in group I but should be placed in group III as it possesses a high degree of beta-adrenoceptor blocking potency in relation to its membrane activity (Prichard, 1974). Finally drugs in group IV have neither ISA nor membrane action, e.g. sotalol, timolol. The cardioselective drugs (Division II) can be similarly sub-divided into groups I-IV according to the presence or absence of ISA or membrane action (Fitzgerald grouped all these together as group V). Lastly there are new beta-adrenergic receptor blocking drugs which in addition have alpha- adrenergic receptor blocking properties (Division III)."}
{"id": "PMID:26374", "title": "Prevention and treatment of premature labour by drugs: review of controlled clinical trials.", "content": "This review sought evidence from 18 controlled clinical trials about the benefits of drugs (hormones, ethanol or beta-sympathomimetic agents) used to prevent premature birth. Of the 16 trials comparing drug with placebo, 13 were judged to be methodologically adequate. In eight trials, drugs were given prophylactically and in five they were given therapeutically. Two of the therapeutic trials found the drug more effective than placebo in postponing delivery. However, only one therapeutic trial and one prophylactic trial found the drug to affect favourably the outcome for the infant. The side effects of the drugs were not systematically studied. Additional clinical trials are needed to justify the use of drugs to inhibit labour.", "contents": "Prevention and treatment of premature labour by drugs: review of controlled clinical trials. This review sought evidence from 18 controlled clinical trials about the benefits of drugs (hormones, ethanol or beta-sympathomimetic agents) used to prevent premature birth. Of the 16 trials comparing drug with placebo, 13 were judged to be methodologically adequate. In eight trials, drugs were given prophylactically and in five they were given therapeutically. Two of the therapeutic trials found the drug more effective than placebo in postponing delivery. However, only one therapeutic trial and one prophylactic trial found the drug to affect favourably the outcome for the infant. The side effects of the drugs were not systematically studied. Additional clinical trials are needed to justify the use of drugs to inhibit labour."}
{"id": "PMID:26375", "title": "Influence of pH on the efficacy of pilocarpine.", "content": "Pilocarpine 4% solutions at pH 4.1 and 5.8 were compared in a double-blind clinical trial on 24 eyes of patients with primary open-angle glaucoma. Each drug was used over a period of 1 week. No significant difference in the lowering of intraocular pressure was found, and the near-neutral solution of pilocarpine was found to be equally stable when compared to the acid solution over a 6-month period.", "contents": "Influence of pH on the efficacy of pilocarpine. Pilocarpine 4% solutions at pH 4.1 and 5.8 were compared in a double-blind clinical trial on 24 eyes of patients with primary open-angle glaucoma. Each drug was used over a period of 1 week. No significant difference in the lowering of intraocular pressure was found, and the near-neutral solution of pilocarpine was found to be equally stable when compared to the acid solution over a 6-month period."}
{"id": "PMID:26378", "title": "Properties of trout hemoglobins reconstituted with unnatural hemes.", "content": "Native globins isolated from trout hemoglobin compoents I and IV have been reconstituted with proto-, meso-, and deuteroheme, and the spectral and functional properties of the reconstituted hemoglobins have been investigated. Equilibrium and kinetic studies allow the following conclusions. (a) The properties of the proto-reconstituted hemoglobins are very similar, or indistinguishable, from those of the native Hb's I and IV. (B) The CO binding kinetics for both proteins were found to be consistent with the equilibrium data: the overall association rate constant increases (and the autocatalytic character of the reaction decreases) in the order proto, meso, deutero. (c) A marked pH dependence of both ligand affinity and cooperativity is maintained in the reconstituted Hb's IV: at pH 6 the fractional saturation with oxygen in air (Root effect) is lower for proto- than for meso- and deutero-Hb IV. The results obtained, including partial photodissociation experiments at different pH values, can be considered, to a first approximation, consistent with the basic features of a simple two-states model.", "contents": "Properties of trout hemoglobins reconstituted with unnatural hemes. Native globins isolated from trout hemoglobin compoents I and IV have been reconstituted with proto-, meso-, and deuteroheme, and the spectral and functional properties of the reconstituted hemoglobins have been investigated. Equilibrium and kinetic studies allow the following conclusions. (a) The properties of the proto-reconstituted hemoglobins are very similar, or indistinguishable, from those of the native Hb's I and IV. (B) The CO binding kinetics for both proteins were found to be consistent with the equilibrium data: the overall association rate constant increases (and the autocatalytic character of the reaction decreases) in the order proto, meso, deutero. (c) A marked pH dependence of both ligand affinity and cooperativity is maintained in the reconstituted Hb's IV: at pH 6 the fractional saturation with oxygen in air (Root effect) is lower for proto- than for meso- and deutero-Hb IV. The results obtained, including partial photodissociation experiments at different pH values, can be considered, to a first approximation, consistent with the basic features of a simple two-states model."}
{"id": "PMID:26379", "title": "Effect of pH on the cross-bridge arrangement in synthetic myosin filaments.", "content": "Synthetic thick filaments were cross-linked with dimethyl suberimidate at various pH values over the range pH 6.8---8.3. The rate of cross-linking myosin heads to the thick filament surface decreases significantly over a narrow pH range (7.4--8.0) despite the fact that the rate of the chemical reaction (amidination of lysine side chains) shows a positive pH dependence. The fall in rate cannot be ascribed to dissociation of the filament during the cross-linking reaction since the sedimentation boundary of the cross-linked filament (pH 8.3) remains unaltered in the presence of high salt (0.5 M). The decreased rate of cross-linking is also not caused by a shift in reactivity of a small number of highly reactive lysine groups, since the time course of cross-linking (pH 7.2) is unaffected by preincubation with a monofunctional imidate ester. Our results suggest that the heads of the myosin molecules move away from the thick filament surface at alkaline pH but are held close to the surface at neutral pH.", "contents": "Effect of pH on the cross-bridge arrangement in synthetic myosin filaments. Synthetic thick filaments were cross-linked with dimethyl suberimidate at various pH values over the range pH 6.8---8.3. The rate of cross-linking myosin heads to the thick filament surface decreases significantly over a narrow pH range (7.4--8.0) despite the fact that the rate of the chemical reaction (amidination of lysine side chains) shows a positive pH dependence. The fall in rate cannot be ascribed to dissociation of the filament during the cross-linking reaction since the sedimentation boundary of the cross-linked filament (pH 8.3) remains unaltered in the presence of high salt (0.5 M). The decreased rate of cross-linking is also not caused by a shift in reactivity of a small number of highly reactive lysine groups, since the time course of cross-linking (pH 7.2) is unaffected by preincubation with a monofunctional imidate ester. Our results suggest that the heads of the myosin molecules move away from the thick filament surface at alkaline pH but are held close to the surface at neutral pH."}
{"id": "PMID:26381", "title": "Modification of Rhodospirillum rubrum ribulose bisphosphate carboxylase with pyridoxal phosphate. 1. Identification of a lysyl residue at the active site.", "content": "Ribulose 1,5-bisphosphate carboxylase isolated from Rhodospirillum rubrum was strongly inhibited by low concentrations of pyridoxal 5'-phosphate. Activity was protected by the substrate ribulose bisphosphate and to a lesser extent by other phosphorylated compounds. Pyridoxal phosphate inhibition was enhanced in the presence of magnesium and bicarbonate, but not in the presence of either compound alone. Concomitant with inhibition of enzyme activity, pyridoxal phosphate forms a Schiff base with the enzyme which is reversible upon dialysis and reducible with sodium borohydride. Subsequent to reduction of the Schiff base with tritiated sodium borohydride, tritiated N6-pyridoxyllysine could be identified in the acid hydrolysate of the enzyme. Only small amounts of this compound were present when the reduction was performed in the presence of carboxyribitol bisphosphate, an analogue of the intermediate formed during the carboxylation reaction. Therefore, it is concluded that pyridoxal phosphate modifies a lysyl residue close to or at the active site of ribulose bisphosphate carboxylase.", "contents": "Modification of Rhodospirillum rubrum ribulose bisphosphate carboxylase with pyridoxal phosphate. 1. Identification of a lysyl residue at the active site. Ribulose 1,5-bisphosphate carboxylase isolated from Rhodospirillum rubrum was strongly inhibited by low concentrations of pyridoxal 5'-phosphate. Activity was protected by the substrate ribulose bisphosphate and to a lesser extent by other phosphorylated compounds. Pyridoxal phosphate inhibition was enhanced in the presence of magnesium and bicarbonate, but not in the presence of either compound alone. Concomitant with inhibition of enzyme activity, pyridoxal phosphate forms a Schiff base with the enzyme which is reversible upon dialysis and reducible with sodium borohydride. Subsequent to reduction of the Schiff base with tritiated sodium borohydride, tritiated N6-pyridoxyllysine could be identified in the acid hydrolysate of the enzyme. Only small amounts of this compound were present when the reduction was performed in the presence of carboxyribitol bisphosphate, an analogue of the intermediate formed during the carboxylation reaction. Therefore, it is concluded that pyridoxal phosphate modifies a lysyl residue close to or at the active site of ribulose bisphosphate carboxylase."}
{"id": "PMID:26382", "title": "Carbon-13 magnetic resonance of carboxymethylated human carbonic anhydrase B. Chemical shift and spin--lattice relaxation studies.", "content": "We have previously prepared Ntau-carbosymethylhistidine-200 human carbonic anhydrase B using 90% [1-13C]bromoacetate and have observed the 13C NMR resonance of the enriched carboxylate now covalently attached in the active site. We report here chemical shift studies of the zinc-free carboxymethylated enzyme and its Co2+-substituted form, as well as relaxation studies of the resonance in the zinc enzyme at three frequencies (15.04, 25.15, and 90.5 MHz). The chemical shift and relaxation data are both consistent with the immobilization of the carboxylate at pH 8 and its approach or coordination to the zinc. The relaxation data indicate that lowering the pH to 5.5 leads to internal motion of the carboxymethyl moiety, consistent with the chemical shift evidence for the disruption of the proposed zinc--carboxylate coordination. Inhibitor binding at either pH 5.5 or 8.0 eliminates whatever internal motion might be present. The relaxation data have been interpreted using theoretical calculations on dipolar and chemical shift anisotropy contributions. The combined results indicate that the catalytic consequences of the carboxymethylation may be due to the proposed zinc--carboxylate coordination and need not result from the disruption of any role that histidine-200 might play in the catalytic mechanism.", "contents": "Carbon-13 magnetic resonance of carboxymethylated human carbonic anhydrase B. Chemical shift and spin--lattice relaxation studies. We have previously prepared Ntau-carbosymethylhistidine-200 human carbonic anhydrase B using 90% [1-13C]bromoacetate and have observed the 13C NMR resonance of the enriched carboxylate now covalently attached in the active site. We report here chemical shift studies of the zinc-free carboxymethylated enzyme and its Co2+-substituted form, as well as relaxation studies of the resonance in the zinc enzyme at three frequencies (15.04, 25.15, and 90.5 MHz). The chemical shift and relaxation data are both consistent with the immobilization of the carboxylate at pH 8 and its approach or coordination to the zinc. The relaxation data indicate that lowering the pH to 5.5 leads to internal motion of the carboxymethyl moiety, consistent with the chemical shift evidence for the disruption of the proposed zinc--carboxylate coordination. Inhibitor binding at either pH 5.5 or 8.0 eliminates whatever internal motion might be present. The relaxation data have been interpreted using theoretical calculations on dipolar and chemical shift anisotropy contributions. The combined results indicate that the catalytic consequences of the carboxymethylation may be due to the proposed zinc--carboxylate coordination and need not result from the disruption of any role that histidine-200 might play in the catalytic mechanism."}
{"id": "PMID:26386", "title": "Analogous effect of protons and inositol hexaphosphate on the alteration of structure of nitrosyl fetal human hemoglobin.", "content": "We have determined the low temperature EPR spectra and room temperature ligand dissociation rate constants of human NO-hemoglobins F and A as a function of pH and inositol hexaphosphate levels in order to assess the contribution of a quaternary structural equilibrium in the two proteins to their spectral and functional properties. Our results are consistent with an increased stability of a ligated low affinity structure in the fetal protein; the functional properties of this structure appear to be essentially the same in the two hemoglobins, even though its stability relative to a high affinity conformation is different. The pH dependence of the NO dissociation constant in both adult and fetal hemoglobin can be assigned primarily to the pH-dependent equilibria of high and low affinity forms as monitored by EPR.", "contents": "Analogous effect of protons and inositol hexaphosphate on the alteration of structure of nitrosyl fetal human hemoglobin. We have determined the low temperature EPR spectra and room temperature ligand dissociation rate constants of human NO-hemoglobins F and A as a function of pH and inositol hexaphosphate levels in order to assess the contribution of a quaternary structural equilibrium in the two proteins to their spectral and functional properties. Our results are consistent with an increased stability of a ligated low affinity structure in the fetal protein; the functional properties of this structure appear to be essentially the same in the two hemoglobins, even though its stability relative to a high affinity conformation is different. The pH dependence of the NO dissociation constant in both adult and fetal hemoglobin can be assigned primarily to the pH-dependent equilibria of high and low affinity forms as monitored by EPR."}
{"id": "PMID:26387", "title": "Spin-label studies of the sulfhydryl environment in bovine plasma albumin. 1. The N--F transition and acid expansion.", "content": "The environment of the sulfhydryl group in plasma albumin was previously characterized by employing spin-labels of varying chain lengths (Hull, H. H., Chang, R., & Kaplan, L. J. (1975) Biochim. Biophys. Acta 400, 132). It was established that the sulfhydryl is in a crevice approximately 10 A deep but this crevice was not identified further. We now report the results of titrating albumin through the acidic conformational transitions while monitoring the electron-spin resonance of the bound nitroxide. With short spin-labels a general change is observed as the pH is lowered but the N--F transition is not discernible. However, with a spin label previously shown to project to the lip on the crevice a clear N--F transition as well as the subsequent acid expansion are observed. These results indicate that the sulfhydryl is in the crevice, formed by the domains of albumin, which opens during the N--F transition. Further results indicate that bound fatty acids do not influence the integrity of the sulfhydryl environment at neutral pH.", "contents": "Spin-label studies of the sulfhydryl environment in bovine plasma albumin. 1. The N--F transition and acid expansion. The environment of the sulfhydryl group in plasma albumin was previously characterized by employing spin-labels of varying chain lengths (Hull, H. H., Chang, R., & Kaplan, L. J. (1975) Biochim. Biophys. Acta 400, 132). It was established that the sulfhydryl is in a crevice approximately 10 A deep but this crevice was not identified further. We now report the results of titrating albumin through the acidic conformational transitions while monitoring the electron-spin resonance of the bound nitroxide. With short spin-labels a general change is observed as the pH is lowered but the N--F transition is not discernible. However, with a spin label previously shown to project to the lip on the crevice a clear N--F transition as well as the subsequent acid expansion are observed. These results indicate that the sulfhydryl is in the crevice, formed by the domains of albumin, which opens during the N--F transition. Further results indicate that bound fatty acids do not influence the integrity of the sulfhydryl environment at neutral pH."}
{"id": "PMID:26388", "title": "Spin-label studies on the sulfhydryl environment in bovine plasma albumin. 2. The neutral transition and the A isomer.", "content": "Since we were able to demonstrate that the sulfhydryl group is located in the crevice which opens during the N--F transition (Cornell, C. N., & Kaplan, L. J. (1978) Biochemistry 17 (preceding paper in this issue), the investigation was extended by characterizing the environment during the N--B transition and in the A isomer. The results indicate that the N--B and N--F transitions are very similar in that the sulfhydryl group moves from a restricted to unhindered environment during both. The use of molecular dipstick technique further demonstrated the similarity between the F and A forms. However, since A is a covalently stabilized form of albumin after a pH dependent transition, it retains its properties during subsequent pH changes rather than reverting to the N form. We were thus able to titrate spin-labeled A through the pH range of the acidic transitions without detecting the N--F transition. Isoelectric focusing analysis of A generated during alkaline aging and purified by SP-Sephadex chromatography indicates that it is a mixture of a small number of albumin forms rather than the large number of components once thought to be formed during aging.", "contents": "Spin-label studies on the sulfhydryl environment in bovine plasma albumin. 2. The neutral transition and the A isomer. Since we were able to demonstrate that the sulfhydryl group is located in the crevice which opens during the N--F transition (Cornell, C. N., & Kaplan, L. J. (1978) Biochemistry 17 (preceding paper in this issue), the investigation was extended by characterizing the environment during the N--B transition and in the A isomer. The results indicate that the N--B and N--F transitions are very similar in that the sulfhydryl group moves from a restricted to unhindered environment during both. The use of molecular dipstick technique further demonstrated the similarity between the F and A forms. However, since A is a covalently stabilized form of albumin after a pH dependent transition, it retains its properties during subsequent pH changes rather than reverting to the N form. We were thus able to titrate spin-labeled A through the pH range of the acidic transitions without detecting the N--F transition. Isoelectric focusing analysis of A generated during alkaline aging and purified by SP-Sephadex chromatography indicates that it is a mixture of a small number of albumin forms rather than the large number of components once thought to be formed during aging."}
{"id": "PMID:26389", "title": "Lipoxygenation activity of purified prostaglandin-forming cyclooxygenase.", "content": "Purified cyclooxygenase, a single enzyme which catalyzes the formation of endoperoxide from arachidonic acid (20:4) in a bis(dioxygenase) reaction, is capable of oxygenating eicosadienoic acid (20:2) at C-11 in a single dioxygenase reaction. The partial oxygenation of 20:2 resembles the formation of prostaglandin from 20:4, with both oxygenation reactions exhibiting similar pH optima, substrate Km values, and cofactor effects including a need for peroxide and an absolute requirement for heme. In addition, those processes known to destroy 20:4 oxygenase activity, such as heat inactivation, inactivation with anti-inflammatory drugs, and turnover-mediated inactivation, have equally destructive effects on 20:2 oxygenase activity. Thus, both oxygenations are catalyzed by one enzyme. All of the above similarities for 20:2 and 20:4 oxygenation demonstrate that C-11 oxygenation is an integral rate-limiting step of cyclooxygenase action rather than a separate reaction resembling that of plant lipoxygenase.", "contents": "Lipoxygenation activity of purified prostaglandin-forming cyclooxygenase. Purified cyclooxygenase, a single enzyme which catalyzes the formation of endoperoxide from arachidonic acid (20:4) in a bis(dioxygenase) reaction, is capable of oxygenating eicosadienoic acid (20:2) at C-11 in a single dioxygenase reaction. The partial oxygenation of 20:2 resembles the formation of prostaglandin from 20:4, with both oxygenation reactions exhibiting similar pH optima, substrate Km values, and cofactor effects including a need for peroxide and an absolute requirement for heme. In addition, those processes known to destroy 20:4 oxygenase activity, such as heat inactivation, inactivation with anti-inflammatory drugs, and turnover-mediated inactivation, have equally destructive effects on 20:2 oxygenase activity. Thus, both oxygenations are catalyzed by one enzyme. All of the above similarities for 20:2 and 20:4 oxygenation demonstrate that C-11 oxygenation is an integral rate-limiting step of cyclooxygenase action rather than a separate reaction resembling that of plant lipoxygenase."}
{"id": "PMID:26390", "title": "The role of chloride ion in photosystem II. I. Effects of chloride ion on photosystem II electron transport and on hydroxylamine inhibition.", "content": "1. Chloroplasts washed with Cl--free, low-salt media (pH 8) containing EDTA, show virtually no DCMU-insensitive silicomolybdate reduction. The activity is readily restored when 10 mM Cl- is added to the reaction mixture. Very similar results were obtained with the other Photosystem II electron acceptor 2,5-dimethylquinone (with dibromothymoquinone), with the Photosystem I electron acceptor FMN, and also with ferricyanide which accepts electrons from both photosystems. 2. Strong Cl--dependence of Hill activity was observed invariably at all pH values tested (5.5--8.3) and in chloroplasts from three different plants: spinach, tobacco and corn (mesophyll). 3. In the absence of added Cl- the functionally Cl--depleted chloroplasts are able to oxidize, through Photosystem II, artificial reductants such as catechol, diphenylcarbazide, ascorbate and H2O2 at rates which are 4--12 times faster than the rate of the residual Hill reaction. 4. The Cl--concentration dependence of Hill activity with dimethylquinone as an electron acceptor is kinetically consistent with the typical enzyme activation mechanism: E(inactive) + Cl- in equilibrium E . Cl- (active), and the apparent activation constant (0.9 mM at pH 7.2) is unchanged by chloroplast fragmentation. 5. The initial phase of the development of inhibition of water oxidation in Cl--depleted chloroplasts during the dark incubation with NH2OH (1/2 H2SO4) is 5 times slower when the incubation medium contains Cl- than when the medium contains NH2OH alone or NH2OH plus acetate ion. (Acetate is shown to be ineffective in stimulating O2 evolution).", "contents": "The role of chloride ion in photosystem II. I. Effects of chloride ion on photosystem II electron transport and on hydroxylamine inhibition. 1. Chloroplasts washed with Cl--free, low-salt media (pH 8) containing EDTA, show virtually no DCMU-insensitive silicomolybdate reduction. The activity is readily restored when 10 mM Cl- is added to the reaction mixture. Very similar results were obtained with the other Photosystem II electron acceptor 2,5-dimethylquinone (with dibromothymoquinone), with the Photosystem I electron acceptor FMN, and also with ferricyanide which accepts electrons from both photosystems. 2. Strong Cl--dependence of Hill activity was observed invariably at all pH values tested (5.5--8.3) and in chloroplasts from three different plants: spinach, tobacco and corn (mesophyll). 3. In the absence of added Cl- the functionally Cl--depleted chloroplasts are able to oxidize, through Photosystem II, artificial reductants such as catechol, diphenylcarbazide, ascorbate and H2O2 at rates which are 4--12 times faster than the rate of the residual Hill reaction. 4. The Cl--concentration dependence of Hill activity with dimethylquinone as an electron acceptor is kinetically consistent with the typical enzyme activation mechanism: E(inactive) + Cl- in equilibrium E . Cl- (active), and the apparent activation constant (0.9 mM at pH 7.2) is unchanged by chloroplast fragmentation. 5. The initial phase of the development of inhibition of water oxidation in Cl--depleted chloroplasts during the dark incubation with NH2OH (1/2 H2SO4) is 5 times slower when the incubation medium contains Cl- than when the medium contains NH2OH alone or NH2OH plus acetate ion. (Acetate is shown to be ineffective in stimulating O2 evolution)."}
{"id": "PMID:26391", "title": "The effect of calcium on the respiratory responses of corn mitochondria.", "content": "Tightly coupled respiring corn mitochondria (Zea mays L.) respond to calcium addition with a transitory respiratory increase, proton extrusion, and Ca2+ binding. The extent of response is dependent upon the level of endogenous phosphate, and a large sustained respiratory increase can be obtained with addition of phosphate. However, calcium does not act as a permeant cation in that it will not penetrate with acetate. It appears that the transitory respiratory increase must be linked to the uptake of a calcium phosphate complex, but there is no evidence that transport of the complex serves to produce an electrophoretic calcium uniport. It is believed that calcium phosphate transport in corn is a constitutive property, and not produced by membrane damage.", "contents": "The effect of calcium on the respiratory responses of corn mitochondria. Tightly coupled respiring corn mitochondria (Zea mays L.) respond to calcium addition with a transitory respiratory increase, proton extrusion, and Ca2+ binding. The extent of response is dependent upon the level of endogenous phosphate, and a large sustained respiratory increase can be obtained with addition of phosphate. However, calcium does not act as a permeant cation in that it will not penetrate with acetate. It appears that the transitory respiratory increase must be linked to the uptake of a calcium phosphate complex, but there is no evidence that transport of the complex serves to produce an electrophoretic calcium uniport. It is believed that calcium phosphate transport in corn is a constitutive property, and not produced by membrane damage."}
{"id": "PMID:26392", "title": "Modes of reduction of nitrogen in heterocysts isolated from Anabaena species.", "content": "N2 fixation (acetylene reduction) has been studied with heterocysts isolated from Anabaena cylindrica and Anabaena 7120. In the presence of ATP and at very low concentrations of sodium dithionite, reducing equivalents for activity of nitrogenase in these cells can be derived from several compounds. In the dark, D-glucose 6-phosphate, 6-phosphogluconate and DL-isocitrate support acetylene reduction via NADPH. In the light, reductant can be generated by Photosystem I.", "contents": "Modes of reduction of nitrogen in heterocysts isolated from Anabaena species. N2 fixation (acetylene reduction) has been studied with heterocysts isolated from Anabaena cylindrica and Anabaena 7120. In the presence of ATP and at very low concentrations of sodium dithionite, reducing equivalents for activity of nitrogenase in these cells can be derived from several compounds. In the dark, D-glucose 6-phosphate, 6-phosphogluconate and DL-isocitrate support acetylene reduction via NADPH. In the light, reductant can be generated by Photosystem I."}
{"id": "PMID:26393", "title": "The involvement of the electrical double layer in the quenching of 9-aminoacridine fluorescence by negatively charged surfaces.", "content": "The addition of 9-aminoacridine monohydrochloride to carboxymethyl-cellulose particles or azolectin liposomes suspended in a low cation medium results in a quenching of its fluorescence. This quenching can be released on the addition of cations. The effectiveness of cations is related only to their valency in the series of salts tested, being monovalent less than divalent less than trivalent, and is independent of the associated anions. These results indicate an electrical rather than a chemical effect, and the relative effectiveness of the various cations can be predicted by the application of classical electrical double layer theory. Fluorescence quenching can also be released on protonation of the fixed negatively charged ionisable groups, and the quenching release curve follows the ionisation curve of these groups. We postulate that when 9-aminoacridine molecules are in the electrical diffuse layer adjacent to the charged surface their fluorescence is quenched, probably due to aggregate formation. As cations are added the 9-aminoacridine concentration at the surface falls as it is displaced into the bulk solution, where it shows a high fluorescence yield with a fluorescence lifetime of 16.3 ns. The fluorescence quenching is associated with an absorbance decrease, which is pronounced with carboxymethyl-cellulose particles and can probably be attributed to self-shielding. The negative charges carried by lipoprotein membranes are primarily due to carboxyl and phosphate groups. Therefore these results with carboxymethyl-cellulose (carboxyl) and azolectin (phosphate) support our earlier suggestion that 9-aminoacridine may be used to probe the electrical double layer associated with negatively charged biological membranes.", "contents": "The involvement of the electrical double layer in the quenching of 9-aminoacridine fluorescence by negatively charged surfaces. The addition of 9-aminoacridine monohydrochloride to carboxymethyl-cellulose particles or azolectin liposomes suspended in a low cation medium results in a quenching of its fluorescence. This quenching can be released on the addition of cations. The effectiveness of cations is related only to their valency in the series of salts tested, being monovalent less than divalent less than trivalent, and is independent of the associated anions. These results indicate an electrical rather than a chemical effect, and the relative effectiveness of the various cations can be predicted by the application of classical electrical double layer theory. Fluorescence quenching can also be released on protonation of the fixed negatively charged ionisable groups, and the quenching release curve follows the ionisation curve of these groups. We postulate that when 9-aminoacridine molecules are in the electrical diffuse layer adjacent to the charged surface their fluorescence is quenched, probably due to aggregate formation. As cations are added the 9-aminoacridine concentration at the surface falls as it is displaced into the bulk solution, where it shows a high fluorescence yield with a fluorescence lifetime of 16.3 ns. The fluorescence quenching is associated with an absorbance decrease, which is pronounced with carboxymethyl-cellulose particles and can probably be attributed to self-shielding. The negative charges carried by lipoprotein membranes are primarily due to carboxyl and phosphate groups. Therefore these results with carboxymethyl-cellulose (carboxyl) and azolectin (phosphate) support our earlier suggestion that 9-aminoacridine may be used to probe the electrical double layer associated with negatively charged biological membranes."}
{"id": "PMID:26394", "title": "Effect of nucleotides on potential and pH changes across the thylakoid membrane of spinach chloroplasts.", "content": "With appropriate preparations of spinish chloroplasts we observe three distinct effects of the nucleotides: 1. An accelaration of the dark decay of the light induced 520 nm absorbance change after ATP addition. 2. An acidification of the internal space of the thylakoids after ATP addition in darkness. 3. A dark ATPase activity which is regulated by the deltapH across the membrane. We conclude that the effect of the nucleoside triphosphates on the 520 nm signal is linked to a change of the proton conductivity of the membrane, induced by the formation of a deltapH across the membrane in consequence of the dark ATPase activity. The mode of action of the nucleoside diphosphates in the presence of inorganic phosphate on the 520 nm signal is discussed. It is proposed that the effects observed are linked to the hydrolysis of the newly formed nucleoside triphosphates.", "contents": "Effect of nucleotides on potential and pH changes across the thylakoid membrane of spinach chloroplasts. With appropriate preparations of spinish chloroplasts we observe three distinct effects of the nucleotides: 1. An accelaration of the dark decay of the light induced 520 nm absorbance change after ATP addition. 2. An acidification of the internal space of the thylakoids after ATP addition in darkness. 3. A dark ATPase activity which is regulated by the deltapH across the membrane. We conclude that the effect of the nucleoside triphosphates on the 520 nm signal is linked to a change of the proton conductivity of the membrane, induced by the formation of a deltapH across the membrane in consequence of the dark ATPase activity. The mode of action of the nucleoside diphosphates in the presence of inorganic phosphate on the 520 nm signal is discussed. It is proposed that the effects observed are linked to the hydrolysis of the newly formed nucleoside triphosphates."}
{"id": "PMID:26396", "title": "Photosynthetic electron transport and phosphorylation reactions in thylakoid membranes from the blue-green alga Anacystis nidulans.", "content": "Thylakoid membranes were prepared from the blue-green alga, Anacystis nidulans with lysozyme treatment and a short period of sonic oscillation. The thylakoid membrane preparation was highly active in the electron transport reactions such as the Hill reactions with ferricyanide and with 2,6-dichlorophenolindophenol, the Mehler reaction mediated by methyl viologen and the system 1 reaction with methyl viologen as an electron acceptor and 2,6-dichlorophenolindophenol and ascorbate as an electron donor system. The Hill reaction with ferricyanide and the system 1 reaction was stimulated by the phosphorylating conditions. The cyclic and non-cyclic phosphorylation was also active. These findings suggest that the preparation of thylakoid membranes retained the electron transport system from H2O to reaction center 1, and that the phosphorylation reaction was coupled to the Hill reaction and the system 1 reaction.", "contents": "Photosynthetic electron transport and phosphorylation reactions in thylakoid membranes from the blue-green alga Anacystis nidulans. Thylakoid membranes were prepared from the blue-green alga, Anacystis nidulans with lysozyme treatment and a short period of sonic oscillation. The thylakoid membrane preparation was highly active in the electron transport reactions such as the Hill reactions with ferricyanide and with 2,6-dichlorophenolindophenol, the Mehler reaction mediated by methyl viologen and the system 1 reaction with methyl viologen as an electron acceptor and 2,6-dichlorophenolindophenol and ascorbate as an electron donor system. The Hill reaction with ferricyanide and the system 1 reaction was stimulated by the phosphorylating conditions. The cyclic and non-cyclic phosphorylation was also active. These findings suggest that the preparation of thylakoid membranes retained the electron transport system from H2O to reaction center 1, and that the phosphorylation reaction was coupled to the Hill reaction and the system 1 reaction."}
{"id": "PMID:26397", "title": "Kinetic study of photoregeneration process of digitonin-solubilized squid rhodopsin.", "content": "In the photoregeneration process of squid rhodopsin, an intermediate has been found at neutral pH values (phosphate buffer) with a flash light (lambda greater than 540 nm). An intermediate R430, with the 11-cis retinal as chromophore, is produced from metarhodopsin in light and is converted to rhodopsin through the processes R430 leads to P380 and P380 leads to rhodopsin. The pH dependence of the velocity of the conversions suggests that processes R430 leads to P380 and P380 leads to rhodopsin involve a protolytic reaction and that the ionized group is a histidine residue of opsin. Kinetic parameters show that the largest conformational change in opsin occurs in the conversion of R430 leads to P380.", "contents": "Kinetic study of photoregeneration process of digitonin-solubilized squid rhodopsin. In the photoregeneration process of squid rhodopsin, an intermediate has been found at neutral pH values (phosphate buffer) with a flash light (lambda greater than 540 nm). An intermediate R430, with the 11-cis retinal as chromophore, is produced from metarhodopsin in light and is converted to rhodopsin through the processes R430 leads to P380 and P380 leads to rhodopsin. The pH dependence of the velocity of the conversions suggests that processes R430 leads to P380 and P380 leads to rhodopsin involve a protolytic reaction and that the ionized group is a histidine residue of opsin. Kinetic parameters show that the largest conformational change in opsin occurs in the conversion of R430 leads to P380."}
{"id": "PMID:26398", "title": "The stimulation of Na+ uptake in frog skin by uranyl ions.", "content": "1. The Na+ uptake in the isolated from skin of Rana esculenta was measured by the short-circuit current (Isc). Uranyl ions increase at pH 5.5 the Isc up to 200% at concentrations of 10 mM. The half-maximal value for this effect is at about 1 mM uranyl salt. 2. The effect is (a) specific for the Na+-selective membrane, (b) fully reversible. No stimulation can be seen in presence of 1 mM H+ or 0.1 mM amiloride. 3. The decrease of the sodium permeability of the apical membrane (PNa), normally induced by increasing concentrations of Na+ in the mucosal solution, %Na]o, is partially prevented by uranyl ions. The apparent Michaelis constant of the saturable Na+ uptake is shifted to much higher values. 4. A comparison between the uranyl effect and similar effects of the other drugs leads to the conclusion that uranyl ions might act in a polar hydrophobic environment, possibly by combining with phosphate groups (of phospholipids), and, thus, enhancing Na+ permeability by changes in tertiary structure near each Na channel. The interaction of mucosal Na+ with their receptor, normally triggering the [Na]o-dependent decrease of PNa, is thought to be diminished by uranyl association in a neighbouring region, causing a noncompetitive stimulation of the Na+ translocation though the apical frog skin membrane.", "contents": "The stimulation of Na+ uptake in frog skin by uranyl ions. 1. The Na+ uptake in the isolated from skin of Rana esculenta was measured by the short-circuit current (Isc). Uranyl ions increase at pH 5.5 the Isc up to 200% at concentrations of 10 mM. The half-maximal value for this effect is at about 1 mM uranyl salt. 2. The effect is (a) specific for the Na+-selective membrane, (b) fully reversible. No stimulation can be seen in presence of 1 mM H+ or 0.1 mM amiloride. 3. The decrease of the sodium permeability of the apical membrane (PNa), normally induced by increasing concentrations of Na+ in the mucosal solution, %Na]o, is partially prevented by uranyl ions. The apparent Michaelis constant of the saturable Na+ uptake is shifted to much higher values. 4. A comparison between the uranyl effect and similar effects of the other drugs leads to the conclusion that uranyl ions might act in a polar hydrophobic environment, possibly by combining with phosphate groups (of phospholipids), and, thus, enhancing Na+ permeability by changes in tertiary structure near each Na channel. The interaction of mucosal Na+ with their receptor, normally triggering the [Na]o-dependent decrease of PNa, is thought to be diminished by uranyl association in a neighbouring region, causing a noncompetitive stimulation of the Na+ translocation though the apical frog skin membrane."}
{"id": "PMID:26400", "title": "Pyranine as a sensitive pH probe for liposome interiors and surfaces. pH gradients across phospholipid vesicles.", "content": "Pyranine is shown to be a convenient and sensitive probe for reporting pH values, pHi, at the interior of anionic and at the outer surface of cationic liposomes. It is well shielded from the phospholipid headgroups by water molecules in the interior of anionic liposomes, but it is bound to the surface of cationic liposomes. Hydrogen ion concentrations outside the liposomes, 'bulk pH values', pHo, were measured by a combination electrode. While pHi = pHo for neutral, pHi less than pHo for anionic and pHi greater than pHo for cationic liposomes prepared in 5.0 . 10(-3) M phosphate buffers. pKa values for the ionization of pyranine were 7.22 +/- 0.04 and 6.00 +/- 0.05 in water and at the external surface of cationic liposomes. The surface potential for cationic liposomes containing dipalmitoyl-DL-alpha-phosphatidylcholine, cholesterol and octadecylamine in the molar ratio of 1.00 : 0.634 : 1.01, were calcuated to be +72.2 mV. Proton permeabilities were measured for single and multicompartment anionic liposomes. Transfer of anionic liposomes prepared at a given pH to a solution of different pH resulted in a pH gradient if sodium phosphate or borate were used as buffers. In the presence of sodium acetate proton equilibration is promptly established.", "contents": "Pyranine as a sensitive pH probe for liposome interiors and surfaces. pH gradients across phospholipid vesicles. Pyranine is shown to be a convenient and sensitive probe for reporting pH values, pHi, at the interior of anionic and at the outer surface of cationic liposomes. It is well shielded from the phospholipid headgroups by water molecules in the interior of anionic liposomes, but it is bound to the surface of cationic liposomes. Hydrogen ion concentrations outside the liposomes, 'bulk pH values', pHo, were measured by a combination electrode. While pHi = pHo for neutral, pHi less than pHo for anionic and pHi greater than pHo for cationic liposomes prepared in 5.0 . 10(-3) M phosphate buffers. pKa values for the ionization of pyranine were 7.22 +/- 0.04 and 6.00 +/- 0.05 in water and at the external surface of cationic liposomes. The surface potential for cationic liposomes containing dipalmitoyl-DL-alpha-phosphatidylcholine, cholesterol and octadecylamine in the molar ratio of 1.00 : 0.634 : 1.01, were calcuated to be +72.2 mV. Proton permeabilities were measured for single and multicompartment anionic liposomes. Transfer of anionic liposomes prepared at a given pH to a solution of different pH resulted in a pH gradient if sodium phosphate or borate were used as buffers. In the presence of sodium acetate proton equilibration is promptly established."}
{"id": "PMID:26401", "title": "Interaction between NADPH-cytochrome P-450 reductase and hepatic microsomes.", "content": "Solubilized NADPH-cytochrome P-450 reductase has been purified from liver microsomes of phenobarbital-treated rats. When added to microsomes, the reductase enhances the monoxygenase, such as aryl hydrocarbon hydroxylase, ethoxycoumarin O-dealkylase, and benzphetamine N-demethylase, activities. The enhancement can be observed with microsomes prepared from phenobarbital- or 3-methylcholanthrene-treated, or non-treated rats. The added reductase is believed to be incorporated into the microsomal membrane, and the rate of the incorporation can be assayed by measuring the enhancement in ethoxycoumarin dealkylase activity. It requires a 30 min incubation at 37 degrees C for maximal incorporation and the process is much slower at lower temperatures. The temperature affects the rate but not the extent of the incorporation. After the incorporation, the enriched microsomes can be separated from the unbound reductase by gel filtration with a Sepharose 4B column. The relationship among the reductase added, reductase bound and the enhancement in hydroxylase activity has been examined. The relationship between the reductase level and the aryl hydrocarbon hydroxylase activity has also been studied with trypsin-treated microsomes. The trypsin treatment removes the reductase from the microsomes, and the decrease in reductase activity is accompanied by a parallel decrease in aryl hydrocarbon hydroxylase activity. When purified reductase is added, the treated microsomes are able to gain aryl hydrocarbon hydroxylase activity to a level comparable to that which can be obtained with normal microsomes. The present study demonstrates that purified NADPH-cytochrome P-450 reductase can be incorporated into the microsomal membrane and the incorporated reductase can interact with the cytochrome P-450 molecules in the membrane, possibly in the same mode as the endogenous reductase molecules. The result is consistent with a non-rigid model for the organization of cytochrome P-450 and NADPH-cytochrome P-450 reductase in the microsomal membrane.", "contents": "Interaction between NADPH-cytochrome P-450 reductase and hepatic microsomes. Solubilized NADPH-cytochrome P-450 reductase has been purified from liver microsomes of phenobarbital-treated rats. When added to microsomes, the reductase enhances the monoxygenase, such as aryl hydrocarbon hydroxylase, ethoxycoumarin O-dealkylase, and benzphetamine N-demethylase, activities. The enhancement can be observed with microsomes prepared from phenobarbital- or 3-methylcholanthrene-treated, or non-treated rats. The added reductase is believed to be incorporated into the microsomal membrane, and the rate of the incorporation can be assayed by measuring the enhancement in ethoxycoumarin dealkylase activity. It requires a 30 min incubation at 37 degrees C for maximal incorporation and the process is much slower at lower temperatures. The temperature affects the rate but not the extent of the incorporation. After the incorporation, the enriched microsomes can be separated from the unbound reductase by gel filtration with a Sepharose 4B column. The relationship among the reductase added, reductase bound and the enhancement in hydroxylase activity has been examined. The relationship between the reductase level and the aryl hydrocarbon hydroxylase activity has also been studied with trypsin-treated microsomes. The trypsin treatment removes the reductase from the microsomes, and the decrease in reductase activity is accompanied by a parallel decrease in aryl hydrocarbon hydroxylase activity. When purified reductase is added, the treated microsomes are able to gain aryl hydrocarbon hydroxylase activity to a level comparable to that which can be obtained with normal microsomes. The present study demonstrates that purified NADPH-cytochrome P-450 reductase can be incorporated into the microsomal membrane and the incorporated reductase can interact with the cytochrome P-450 molecules in the membrane, possibly in the same mode as the endogenous reductase molecules. The result is consistent with a non-rigid model for the organization of cytochrome P-450 and NADPH-cytochrome P-450 reductase in the microsomal membrane."}
{"id": "PMID:26402", "title": "Influence of (DL)-propranolol and Ca2+ on membrane potential and amino acid transport in Ehrlich ascites tumor cells.", "content": "(1) (DL)-Propranolol and Ca2+ are shown to alter the transmembrane potential difference of Ehrlich ascites tumor cells as measured by means of the cyanine dye, 3,3'-dipropyl-2,2'-thiodicarbocyanine iodide, whose fluorescent intensity changes as a function of membrane potential. (2) The changes in membrane potential elicited by these agents are dependent of the external K+ concentration in a manner which suggest that the potential changes result from a specific increase in the permeability of the plasma membrane to K+. (3) Na+-dependent amino acid transport in the presence of propranolol can be modulated by varying the external K+ concentration (K+o). The initial rate of uptake is stimulated by propranolol at low K+o and inhibited at high K+o. The change in transport rate is nearly directly proportional to the natural logarithm of [K+]o in the presence of propranolol. (4) ATP depletion of the cells by preincubation with rotenone abolishes the changes in fluorescence and amino acid uptake seen with propranolol as a function of K+o. Restoration of cellular ATP with glucose in presence of Ca2+ restores both fluorescence and amino acid transport changes which occur in response to propranolol. (5) The fluorescence changes and amino acid transport changes in response to propranolol are pH dependent, with little effect seen at pH6. (6) It is concluded that the rate of Na+-dependent amino acid uptake is a function of membrane potential and is dependent on the electrochemical potential difference for Na+.", "contents": "Influence of (DL)-propranolol and Ca2+ on membrane potential and amino acid transport in Ehrlich ascites tumor cells. (1) (DL)-Propranolol and Ca2+ are shown to alter the transmembrane potential difference of Ehrlich ascites tumor cells as measured by means of the cyanine dye, 3,3'-dipropyl-2,2'-thiodicarbocyanine iodide, whose fluorescent intensity changes as a function of membrane potential. (2) The changes in membrane potential elicited by these agents are dependent of the external K+ concentration in a manner which suggest that the potential changes result from a specific increase in the permeability of the plasma membrane to K+. (3) Na+-dependent amino acid transport in the presence of propranolol can be modulated by varying the external K+ concentration (K+o). The initial rate of uptake is stimulated by propranolol at low K+o and inhibited at high K+o. The change in transport rate is nearly directly proportional to the natural logarithm of [K+]o in the presence of propranolol. (4) ATP depletion of the cells by preincubation with rotenone abolishes the changes in fluorescence and amino acid uptake seen with propranolol as a function of K+o. Restoration of cellular ATP with glucose in presence of Ca2+ restores both fluorescence and amino acid transport changes which occur in response to propranolol. (5) The fluorescence changes and amino acid transport changes in response to propranolol are pH dependent, with little effect seen at pH6. (6) It is concluded that the rate of Na+-dependent amino acid uptake is a function of membrane potential and is dependent on the electrochemical potential difference for Na+."}
{"id": "PMID:26404", "title": "Transport of alpha-aminoisobutyrate by cells and membrane vesicles of Pseudomonas fluorescens.", "content": "The transport of alpha-aminoisobutyrate into Pseudomonas fluorescens NCIB 8865 and membrane vesicles prepared from this organism has been studied. Uptake by cells was mediated by two active transport systems with different apparent Km values, while transport into membrane vesicles was mediated by a single component. The effect of inhibitors on the energy-coupling mechanism for alpha-aminoisobutyrate transport in these systems suggests that a membrane potential may play a significant role in supporting alpha-aminoisobutyrate transport. The magnitude of the membrane potential in the vesicle system, and the sensitivity of its generation to inhibitors, has been measured using 137Cs in the presence of valinomycin. Direct attempts to demonstrate a protonsymport mechanism for alpha-aminoisobutyrate transport were negative.", "contents": "Transport of alpha-aminoisobutyrate by cells and membrane vesicles of Pseudomonas fluorescens. The transport of alpha-aminoisobutyrate into Pseudomonas fluorescens NCIB 8865 and membrane vesicles prepared from this organism has been studied. Uptake by cells was mediated by two active transport systems with different apparent Km values, while transport into membrane vesicles was mediated by a single component. The effect of inhibitors on the energy-coupling mechanism for alpha-aminoisobutyrate transport in these systems suggests that a membrane potential may play a significant role in supporting alpha-aminoisobutyrate transport. The magnitude of the membrane potential in the vesicle system, and the sensitivity of its generation to inhibitors, has been measured using 137Cs in the presence of valinomycin. Direct attempts to demonstrate a protonsymport mechanism for alpha-aminoisobutyrate transport were negative."}
{"id": "PMID:26405", "title": "How much is secondary structure responsible for resistance  of double-stranded RNA to pancreatic ribonuclease A?", "content": "1. Double-stranded f2 sus11 or Qbeta RNAs, resistant to bovine pancreatic RNAase A in 0.15 M NaCl/0.015 M sodium citrate (SSC), are quickly and completely degraded at 10-fold lower ionic strength (0.1 X SSC) under otherwise similar conditions. At this ionic strength the secondary structure of double-stranded RNA is maintained, as judged by the following: (a) the unchanged resistance of double-stranded RNA and DNA, under similar low ionic strength conditions, to nuclease S1 from Aspergillus oryzae, in contrast with the sensitivity of the corresponding denatured nucleic acids to this enzyme, specific for single-stranded RNA and DNA; (b) the co-operative pattern of the thermal-transition profile of double-stranded RNA (with a Tm of 89 degrees C) in 0.1 X SSC. 2. Whereas in SSC bovine seminal RNAase (RNAase BS-1) and whale pancreatic RNAase show an activity on double-stranded RNA significantly higher than that of RNAase A, in 0.1 X SSC the activity of the latter enzyme on this substrate becomes distinctly higher than that of RNAase BS-1, and similar to that of whale RNAase. 3. From these results it is deduced that the secondary structure is probably not the only nor the most important variable in determining the susceptibility double-stranded RNA to ribonuclease. Other factors, such as the effect of ionic strength on the enzyme and/or the binding of enzyme to nucleic acids, may play an important role in the process of double-stranded RNA degradation by ribonucleases specific for single-stranded RNA.", "contents": "How much is secondary structure responsible for resistance  of double-stranded RNA to pancreatic ribonuclease A? 1. Double-stranded f2 sus11 or Qbeta RNAs, resistant to bovine pancreatic RNAase A in 0.15 M NaCl/0.015 M sodium citrate (SSC), are quickly and completely degraded at 10-fold lower ionic strength (0.1 X SSC) under otherwise similar conditions. At this ionic strength the secondary structure of double-stranded RNA is maintained, as judged by the following: (a) the unchanged resistance of double-stranded RNA and DNA, under similar low ionic strength conditions, to nuclease S1 from Aspergillus oryzae, in contrast with the sensitivity of the corresponding denatured nucleic acids to this enzyme, specific for single-stranded RNA and DNA; (b) the co-operative pattern of the thermal-transition profile of double-stranded RNA (with a Tm of 89 degrees C) in 0.1 X SSC. 2. Whereas in SSC bovine seminal RNAase (RNAase BS-1) and whale pancreatic RNAase show an activity on double-stranded RNA significantly higher than that of RNAase A, in 0.1 X SSC the activity of the latter enzyme on this substrate becomes distinctly higher than that of RNAase BS-1, and similar to that of whale RNAase. 3. From these results it is deduced that the secondary structure is probably not the only nor the most important variable in determining the susceptibility double-stranded RNA to ribonuclease. Other factors, such as the effect of ionic strength on the enzyme and/or the binding of enzyme to nucleic acids, may play an important role in the process of double-stranded RNA degradation by ribonucleases specific for single-stranded RNA."}
{"id": "PMID:26406", "title": "Incomplete aminoacylation of tRNALeu catalyzed in vitro by leucyl-tRNA synthetase from Escherichia coli B.", "content": "The extent of esterification of [14C] leucine into Escherichia coli B tRNALeu apparently depends on the concentration of leucyl-tRNA synthetase. The effect is more pronounced at pH 9.0 than at pH 7.4. When reciprocals of leucyl-tRNA concentration at plateau [aa-tRNA]-1 are plotted against reciprocals of initial velocities vo-1 of aminoacylations a straight line is obtained with a slope equal to the rate constant of non-enzymatic deacylation of leucyl-tRNA. Factors which change the stability of leucyl-tRNA, e.g. pH and temperature, also change the shape of the function [aa-tRNA]-1 vs. vo-1. The data are consistent with the idea that the rate constant of spontaneous deacylation of aminoacyl-tRNA is the factor which accounts for the dependence of the level of aminoacylation on initial velocity of aminoacylation.", "contents": "Incomplete aminoacylation of tRNALeu catalyzed in vitro by leucyl-tRNA synthetase from Escherichia coli B. The extent of esterification of [14C] leucine into Escherichia coli B tRNALeu apparently depends on the concentration of leucyl-tRNA synthetase. The effect is more pronounced at pH 9.0 than at pH 7.4. When reciprocals of leucyl-tRNA concentration at plateau [aa-tRNA]-1 are plotted against reciprocals of initial velocities vo-1 of aminoacylations a straight line is obtained with a slope equal to the rate constant of non-enzymatic deacylation of leucyl-tRNA. Factors which change the stability of leucyl-tRNA, e.g. pH and temperature, also change the shape of the function [aa-tRNA]-1 vs. vo-1. The data are consistent with the idea that the rate constant of spontaneous deacylation of aminoacyl-tRNA is the factor which accounts for the dependence of the level of aminoacylation on initial velocity of aminoacylation."}
{"id": "PMID:26407", "title": "Hydroxymethylglutaryl-coenzyme A reductase. Purification and properties of the enzyme from Fusarium oxysporum.", "content": "The hydroxymethylglutaryl-coenzyme A reductase (mevalonate:NADP+ oxidoreductase, EC 1.1.1.34) system in Fusarium oxysporum, a soil inhabiting plant pathogen, has been examined. Two forms of the enzyme catalyzing the conversion of hydroxymethylglutaryl-coenzyme A were obtained in the supernatant after precipitation at 75% (NH4)2SO4 saturation of the soluble culture extract which was previously separated from cell wall, mitochondria and microsomes. The two forms of the enzyme were separated electrophoretically. A third form, contained in the precipitate obtained at 35--75% (NH4)2SO4 saturation of the same extract, was further purified by Sephadex G-50 column chromatography. This purified form moved as a single band in sodium dodecyl sulphate electrophoresis and in immunological tests and has a molecular weight of 11 000. The apparent Michaelis constant for the substrate hydroxymethylglutaryl-coenzyme A is 21 micron at 2 micron NADP. NADPH is a more efficient reductant on a molar basis than NADH for the deacylation of the hydroxymethylglutaryl-coenzyme A substrate. Optimum activity of the enzyme was obtained at pH 7.4 and 37 degrees C. The enzyme demonstrated no cold sensitivity but rather was more stable at 4 degrees C than at 25 degrees C. The protection with dithiothreitol, though minimal compared to other systems, was more effective at the higher temperature.", "contents": "Hydroxymethylglutaryl-coenzyme A reductase. Purification and properties of the enzyme from Fusarium oxysporum. The hydroxymethylglutaryl-coenzyme A reductase (mevalonate:NADP+ oxidoreductase, EC 1.1.1.34) system in Fusarium oxysporum, a soil inhabiting plant pathogen, has been examined. Two forms of the enzyme catalyzing the conversion of hydroxymethylglutaryl-coenzyme A were obtained in the supernatant after precipitation at 75% (NH4)2SO4 saturation of the soluble culture extract which was previously separated from cell wall, mitochondria and microsomes. The two forms of the enzyme were separated electrophoretically. A third form, contained in the precipitate obtained at 35--75% (NH4)2SO4 saturation of the same extract, was further purified by Sephadex G-50 column chromatography. This purified form moved as a single band in sodium dodecyl sulphate electrophoresis and in immunological tests and has a molecular weight of 11 000. The apparent Michaelis constant for the substrate hydroxymethylglutaryl-coenzyme A is 21 micron at 2 micron NADP. NADPH is a more efficient reductant on a molar basis than NADH for the deacylation of the hydroxymethylglutaryl-coenzyme A substrate. Optimum activity of the enzyme was obtained at pH 7.4 and 37 degrees C. The enzyme demonstrated no cold sensitivity but rather was more stable at 4 degrees C than at 25 degrees C. The protection with dithiothreitol, though minimal compared to other systems, was more effective at the higher temperature."}
{"id": "PMID:26408", "title": "Purification and characterization of homogeneous assimilatory reduced nicotinamide adenine dinucleotide phosphate-nitrate reductase from Neurospora crassa.", "content": "Neurospora crassa wild type STA4 NADPH-nitrate reductase (NADPH : nitrate oxidoreductase, EC 1.6.6.3) has been purified 5000-fold with an overall yield of 25--50%. The final purified enzyme contained 4 associated enzymatic activities: NADPH-nitrate reductase, FADH2-nitrate reductase, reduced methyl viologen-nitrate reductase and NADPH-cytochrome c reductase. Polyacrylamide gel electrophoresis yielded 1 major and 1 minor protein band and both bands exhibited NADPH-nitrate and reduced methyl viologen-nitrate reductase activities. SDS gel electrophoresis yielded 2 protein bands corresponding to molecular weights of 115 000 and 130 000. A single N-terminal amino acid (glutamic acid) was found and proteolytic mapping for the two separated subunits appeared similar. Purified NADPH-nitrate reductase contained 1 mol of molybdenum and 2 mol of cytochrome b557 per mol protein. Non-heme iron, zinc and copper were not detectable. It is proposed that the Neurospora assimilatory NADPH-nitrate reductase consists of 2 similar cytochrome b557-containing 4.5-S subunits linked together by one molybdenum cofactor. A revised electron flow scheme is presented. p-Hydroxymercuribenzoate inhibition was reversed by sulfhydryl reagents. Inhibitory pattern of p-hydroxymercuribenzoate and phenylglyoxal revealed accessible sulfhydryl and arginyl residue(s) as functional group(s) in the earlier part of electron transport chain as possibly the binding site of NADPH or FAD.", "contents": "Purification and characterization of homogeneous assimilatory reduced nicotinamide adenine dinucleotide phosphate-nitrate reductase from Neurospora crassa. Neurospora crassa wild type STA4 NADPH-nitrate reductase (NADPH : nitrate oxidoreductase, EC 1.6.6.3) has been purified 5000-fold with an overall yield of 25--50%. The final purified enzyme contained 4 associated enzymatic activities: NADPH-nitrate reductase, FADH2-nitrate reductase, reduced methyl viologen-nitrate reductase and NADPH-cytochrome c reductase. Polyacrylamide gel electrophoresis yielded 1 major and 1 minor protein band and both bands exhibited NADPH-nitrate and reduced methyl viologen-nitrate reductase activities. SDS gel electrophoresis yielded 2 protein bands corresponding to molecular weights of 115 000 and 130 000. A single N-terminal amino acid (glutamic acid) was found and proteolytic mapping for the two separated subunits appeared similar. Purified NADPH-nitrate reductase contained 1 mol of molybdenum and 2 mol of cytochrome b557 per mol protein. Non-heme iron, zinc and copper were not detectable. It is proposed that the Neurospora assimilatory NADPH-nitrate reductase consists of 2 similar cytochrome b557-containing 4.5-S subunits linked together by one molybdenum cofactor. A revised electron flow scheme is presented. p-Hydroxymercuribenzoate inhibition was reversed by sulfhydryl reagents. Inhibitory pattern of p-hydroxymercuribenzoate and phenylglyoxal revealed accessible sulfhydryl and arginyl residue(s) as functional group(s) in the earlier part of electron transport chain as possibly the binding site of NADPH or FAD."}
{"id": "PMID:26409", "title": "Characterization of guanylate cyclase of rod outer segments of the bovine retina.", "content": "Guanylate cyclase (GTP pyrophosphate-lyse (cyclizing), EC 4.6.1.2.) of bovine retinal rod outer segments is almost completely particulate, i.e. associated with rod outer segment membranes. In contrast to particulate guanylate cyclase in other tissues, treatment of rod outer segments with Triton X-100 does not solublize the enzyme but inhibits it. Enzyme activity is dependent on the presence of divalent cation, especially Mn2+ with only poor activation by Mg2+ (10-fold lower) and no activation seen with other cation. Ezpression of maximal activity required Nm2+ and GTP in equimolar concentrations with an apparent Km of 8 . 10(-4) M and V of 10 nmol/min per mg protein. Excess of Mn2+ over that required for the formation of the Mn . GTP complex was inhibitory. Ca2+, Ba2+ and Co2+ inhibited enzyme activity when assayed with the Mn . GTP substrate complex. In the presence of a fixed concentration of 1mM Mn2+, the enzyme exhibited strong negative cooperative interactions with GTP, characterized by an intermediary plateau region in the substrate vs. enzyme activity curve, a curve of downward concavity in the double reciprocal plot and a Hill coefficient of 0.5. Nucleotides such as ITP, ATP and UTP at higher concentrations (1 mM) stimulates activity by 40%. NaN3 has no effect on the guanylate cyclase. It is thus possible that the guanylate cyclase may be regulated in vivo by both the metal : GTP substrate ratio and the free divalent cation concentration as well as by the ATP concentration and thus play an important but yet undefined role in the visual process.", "contents": "Characterization of guanylate cyclase of rod outer segments of the bovine retina. Guanylate cyclase (GTP pyrophosphate-lyse (cyclizing), EC 4.6.1.2.) of bovine retinal rod outer segments is almost completely particulate, i.e. associated with rod outer segment membranes. In contrast to particulate guanylate cyclase in other tissues, treatment of rod outer segments with Triton X-100 does not solublize the enzyme but inhibits it. Enzyme activity is dependent on the presence of divalent cation, especially Mn2+ with only poor activation by Mg2+ (10-fold lower) and no activation seen with other cation. Ezpression of maximal activity required Nm2+ and GTP in equimolar concentrations with an apparent Km of 8 . 10(-4) M and V of 10 nmol/min per mg protein. Excess of Mn2+ over that required for the formation of the Mn . GTP complex was inhibitory. Ca2+, Ba2+ and Co2+ inhibited enzyme activity when assayed with the Mn . GTP substrate complex. In the presence of a fixed concentration of 1mM Mn2+, the enzyme exhibited strong negative cooperative interactions with GTP, characterized by an intermediary plateau region in the substrate vs. enzyme activity curve, a curve of downward concavity in the double reciprocal plot and a Hill coefficient of 0.5. Nucleotides such as ITP, ATP and UTP at higher concentrations (1 mM) stimulates activity by 40%. NaN3 has no effect on the guanylate cyclase. It is thus possible that the guanylate cyclase may be regulated in vivo by both the metal : GTP substrate ratio and the free divalent cation concentration as well as by the ATP concentration and thus play an important but yet undefined role in the visual process."}
{"id": "PMID:26410", "title": "Isoelectric focusing of carboxypeptidase N.", "content": "Carboxypeptidase N was partially purified on a TEAE-cellulose column and subjected to isoelectric focusing in sucrose gradient columns containing ampholine gradients of pH range 3-10 and 4-8. Activity separated into two major peaks with pI values of pH 3.8 and 4.3. Both peaks were totally converted to an active desialated enzyme with isoelectric point of pH 5.2 to 5.4. These results indicate that carboxypeptidase N is a sialoprotein with at least two forms, differing in sialic acid content, in serum. Catalytic activity is not dependent upon sialic acid but the latter may possibly influence stability since loss of activity occurred in the desialated enzyme with repeat focusing.", "contents": "Isoelectric focusing of carboxypeptidase N. Carboxypeptidase N was partially purified on a TEAE-cellulose column and subjected to isoelectric focusing in sucrose gradient columns containing ampholine gradients of pH range 3-10 and 4-8. Activity separated into two major peaks with pI values of pH 3.8 and 4.3. Both peaks were totally converted to an active desialated enzyme with isoelectric point of pH 5.2 to 5.4. These results indicate that carboxypeptidase N is a sialoprotein with at least two forms, differing in sialic acid content, in serum. Catalytic activity is not dependent upon sialic acid but the latter may possibly influence stability since loss of activity occurred in the desialated enzyme with repeat focusing."}
{"id": "PMID:26411", "title": "Methacrylate gels with epoxide groups as supports for immobilization of enzymes in pH range 3-12.", "content": "Glycidyl methacrylate gels are carriers suitable for attachment of enzymes and for use in affinity chromatography. Experiments on the coupling of glycyl-L-leucine and acetyl-L-leucine to these gels have shown a high pH-dependence of the bond formation between the support and the alpha-amino group (pH optimum 9.7); the coupling reaction between the epoxide group and the carboxyl group is practically pH-independent. Serum albumin and trypsin were attached to a greater extent in acidic than in alkaline media. The effects of time and temperature were also studied. The catalytic action of immobilized trypsin, as well as its use for affinity chromatography of trypsin inhibitor, were studied.", "contents": "Methacrylate gels with epoxide groups as supports for immobilization of enzymes in pH range 3-12. Glycidyl methacrylate gels are carriers suitable for attachment of enzymes and for use in affinity chromatography. Experiments on the coupling of glycyl-L-leucine and acetyl-L-leucine to these gels have shown a high pH-dependence of the bond formation between the support and the alpha-amino group (pH optimum 9.7); the coupling reaction between the epoxide group and the carboxyl group is practically pH-independent. Serum albumin and trypsin were attached to a greater extent in acidic than in alkaline media. The effects of time and temperature were also studied. The catalytic action of immobilized trypsin, as well as its use for affinity chromatography of trypsin inhibitor, were studied."}
{"id": "PMID:26412", "title": "Effects of thiol inhibitors on hepatic guanylate cylase activity.", "content": "Several thiol blocking agents inhibit basal guanylate cyclase activity of 100 000 X g hepatic supernatant fractions and the stimulation of enzyme activity by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), NaN3, NaNO2 and nitroprusside. The relative potency of the thiol blockers as inhibitors was CdCl2 greater than p-hydroxymercuribenzoate greater than N-ethylmaleimide greater than arsenite greater than iodoacetamide. Inhibition of basal and MNNG-responsive soluble guanylate cyclase activities by arsenite was markedly potentiated by an equimolar concentration of 2,3-dimercaprol, but not by mercaptoethanol. Inhibition of soluble guanylate cyclase by either arsenite or CdCl2 was completely reversed by excess 2,3-dimercaprol. Qualitatively similar effects were observed with DE-52 cellulose purified soluble hepatic guanylate cyclase, and suggested an involvement of closely juxtaposed thiol groups in the regulation of enzyme activity. For several reasons inhibition by thiol blockers appeared to be mediated through multiple mechanisms and/or sites of interaction: (1) Concentrations of the thiol inhibitors which had no effect on basal activity strikingly inhibited the responsiveness of the enzyme to a submaximal concentration of MNNG. (2) CdCl2 abolished the action of excess MnCl2 to stimulate purified guanylate cyclase, but was a relatively ineffective inhibitor when MnCl2 and GTP were present in equimolar concentrations. By contrast, arsenite-2,3-dimercaprol was uniformly effective in inhibiting guanylate cyclase activity in the presence or absence of excess MnCl2. (3) Arsenite-2,3-dimercaprol increased the Km for MnGTP (control, 0.13 +/- 0.02 mM; 0.2 mM arsenite-2,3-dimercaprol, 0.31 +/- 0.03 mM), whereas CdCl2 had no effect on this parameter. (4) Hepatic particulate guanylate cyclase activity was significantly inhibited by arsenite 2,3-dimercaprol but not by CdCl2. Thus, the data not only indicate that vicinal dithiol groups are required for expression of basal guanylate cyclase activity and enzyme responses to agonists, but strongly suggest the involvement of more than one interacting site containing free thiol residues.", "contents": "Effects of thiol inhibitors on hepatic guanylate cylase activity. Several thiol blocking agents inhibit basal guanylate cyclase activity of 100 000 X g hepatic supernatant fractions and the stimulation of enzyme activity by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), NaN3, NaNO2 and nitroprusside. The relative potency of the thiol blockers as inhibitors was CdCl2 greater than p-hydroxymercuribenzoate greater than N-ethylmaleimide greater than arsenite greater than iodoacetamide. Inhibition of basal and MNNG-responsive soluble guanylate cyclase activities by arsenite was markedly potentiated by an equimolar concentration of 2,3-dimercaprol, but not by mercaptoethanol. Inhibition of soluble guanylate cyclase by either arsenite or CdCl2 was completely reversed by excess 2,3-dimercaprol. Qualitatively similar effects were observed with DE-52 cellulose purified soluble hepatic guanylate cyclase, and suggested an involvement of closely juxtaposed thiol groups in the regulation of enzyme activity. For several reasons inhibition by thiol blockers appeared to be mediated through multiple mechanisms and/or sites of interaction: (1) Concentrations of the thiol inhibitors which had no effect on basal activity strikingly inhibited the responsiveness of the enzyme to a submaximal concentration of MNNG. (2) CdCl2 abolished the action of excess MnCl2 to stimulate purified guanylate cyclase, but was a relatively ineffective inhibitor when MnCl2 and GTP were present in equimolar concentrations. By contrast, arsenite-2,3-dimercaprol was uniformly effective in inhibiting guanylate cyclase activity in the presence or absence of excess MnCl2. (3) Arsenite-2,3-dimercaprol increased the Km for MnGTP (control, 0.13 +/- 0.02 mM; 0.2 mM arsenite-2,3-dimercaprol, 0.31 +/- 0.03 mM), whereas CdCl2 had no effect on this parameter. (4) Hepatic particulate guanylate cyclase activity was significantly inhibited by arsenite 2,3-dimercaprol but not by CdCl2. Thus, the data not only indicate that vicinal dithiol groups are required for expression of basal guanylate cyclase activity and enzyme responses to agonists, but strongly suggest the involvement of more than one interacting site containing free thiol residues."}
{"id": "PMID:26413", "title": "Lipoxygenase-like enzyme in rat testis microsomes.", "content": "Microsomes, separated from rat testes, were found capable of oxidizing linoleate and arachidonate. The enzyme activity was solubilized with 1% Triton X-100 in acetate buffer (pH 5.0) and purified by affinity chromatography. The overall purification from the starting preparation was approx. 40-fold. The affinity-purified enzyme was almost homogeneous as determined by electrophoresis in polyacrylamide gel. The enzyme was characterized as lipoxygenase-like from its spectrum, specificity, effect of linoleate on its fluorescence and linoleate oxidation products. Three types of compounds separated by thin-layer chromatography were generally present in the lipoxygenase-like enzyme reaction on linoleic acid: substrate fatty acid, polar by-products and hydroperoxides. The hydroperoxides were analyzed by infrared spectra and mass spectrometry and showed the presence of both 9- and 13-hydroxy isomers.", "contents": "Lipoxygenase-like enzyme in rat testis microsomes. Microsomes, separated from rat testes, were found capable of oxidizing linoleate and arachidonate. The enzyme activity was solubilized with 1% Triton X-100 in acetate buffer (pH 5.0) and purified by affinity chromatography. The overall purification from the starting preparation was approx. 40-fold. The affinity-purified enzyme was almost homogeneous as determined by electrophoresis in polyacrylamide gel. The enzyme was characterized as lipoxygenase-like from its spectrum, specificity, effect of linoleate on its fluorescence and linoleate oxidation products. Three types of compounds separated by thin-layer chromatography were generally present in the lipoxygenase-like enzyme reaction on linoleic acid: substrate fatty acid, polar by-products and hydroperoxides. The hydroperoxides were analyzed by infrared spectra and mass spectrometry and showed the presence of both 9- and 13-hydroxy isomers."}
{"id": "PMID:26414", "title": "Properties of hemoglobin G. Ferrara (beta57(E1) Asn replaced by Lys).", "content": "Hemoglobin G. Ferrara is an abnormal human hemoglobin in which an asparagine residue is replaced by a lysyl residue at position beta57 (beta57 Asn replaced by Lys). Oxygen equilibria show that cooperativity and alkaline Bohr effect are maintained to normal levels while the acid Bohr effect appears increased; in addition, a smaller effect of diphosphoglycerate is also observed. Flash photolysis experiments performed as a function of protein concentration show that the fraction of quickly reacting form is always higher than that of human hemoglobin A. This fact, together with the increase of the oxygen affinity observed at acid pH values, may be related to an enhanced dissociation of the molecule into dimers. Several attempts to isolate the native chains by treatment of the protein with p-chloromercuribenzoate were unsuccessful due to the great instability of the isolated variant beta-chains, which precipitated completely during incubation with p-chloromercuribenzoate. Therefore, although the substitution is on the surface of the molecule, there are several properties of hemoglobin G. beta Ferrara which are clearly different from hemoglobin A.", "contents": "Properties of hemoglobin G. Ferrara (beta57(E1) Asn replaced by Lys). Hemoglobin G. Ferrara is an abnormal human hemoglobin in which an asparagine residue is replaced by a lysyl residue at position beta57 (beta57 Asn replaced by Lys). Oxygen equilibria show that cooperativity and alkaline Bohr effect are maintained to normal levels while the acid Bohr effect appears increased; in addition, a smaller effect of diphosphoglycerate is also observed. Flash photolysis experiments performed as a function of protein concentration show that the fraction of quickly reacting form is always higher than that of human hemoglobin A. This fact, together with the increase of the oxygen affinity observed at acid pH values, may be related to an enhanced dissociation of the molecule into dimers. Several attempts to isolate the native chains by treatment of the protein with p-chloromercuribenzoate were unsuccessful due to the great instability of the isolated variant beta-chains, which precipitated completely during incubation with p-chloromercuribenzoate. Therefore, although the substitution is on the surface of the molecule, there are several properties of hemoglobin G. beta Ferrara which are clearly different from hemoglobin A."}
{"id": "PMID:26415", "title": "A proton NMR investigation of proline-24 cis-trans isomerism in corticotropin 1-32 and related peptides.", "content": "250 MHz 1H-NMR studies performed on aqueous solutions of corticotropin1-32, corticotropin1-24, corticotropin15-32, corticotropin20-32 and corticotropin15-24 have allowed the location and the subsequent assignment of the signals of Tyrosine-23 aromatic protons and valine-22 methyl protons. These signals are sensitive to the geometry of proline-24, clearly transcribe its isomerism and yield the ratio of the cis-trans conformers. It is concluded that for large peptides in specific cases, the proton signals of side chains can be used to probe the backbone conformation.", "contents": "A proton NMR investigation of proline-24 cis-trans isomerism in corticotropin 1-32 and related peptides. 250 MHz 1H-NMR studies performed on aqueous solutions of corticotropin1-32, corticotropin1-24, corticotropin15-32, corticotropin20-32 and corticotropin15-24 have allowed the location and the subsequent assignment of the signals of Tyrosine-23 aromatic protons and valine-22 methyl protons. These signals are sensitive to the geometry of proline-24, clearly transcribe its isomerism and yield the ratio of the cis-trans conformers. It is concluded that for large peptides in specific cases, the proton signals of side chains can be used to probe the backbone conformation."}
{"id": "PMID:26416", "title": "Role of Bohr group salt bridges in cooperativity in hemoglobin.", "content": "Possible problems in measuring the first Adair constant, K1, from accurate oxygen equilibrium curves have been investigated. Of these only the presence of small amounts of CO-hemoglobin or hemoglobin dimers had a significant effect. The former can be eliminated by treatment with oxygen, the latter by measuring the concentration-dependence of K1 or working at high protein concentrations. K1 values have been measured for normal hemoglobin at pH 7 and 9, hemoglobin specifically reacted with cyanate at Val 1alpha (alphac2beta2) and des(His 146beta) hemoglobin at pH 7. K1 is equal to KT, the oxygen affinity of the T state of hemoglobin, for all these hemoglobins and was increased in all of them when compared to normal hemoglobin at pH 7. This shows that the breakage of the Bohr group salt bridges by increasing pH or specific modification changes KT. Hence the Bohr group salt bridges break on ligation of the T state and are partially responsible for the free energy of cooperativity.", "contents": "Role of Bohr group salt bridges in cooperativity in hemoglobin. Possible problems in measuring the first Adair constant, K1, from accurate oxygen equilibrium curves have been investigated. Of these only the presence of small amounts of CO-hemoglobin or hemoglobin dimers had a significant effect. The former can be eliminated by treatment with oxygen, the latter by measuring the concentration-dependence of K1 or working at high protein concentrations. K1 values have been measured for normal hemoglobin at pH 7 and 9, hemoglobin specifically reacted with cyanate at Val 1alpha (alphac2beta2) and des(His 146beta) hemoglobin at pH 7. K1 is equal to KT, the oxygen affinity of the T state of hemoglobin, for all these hemoglobins and was increased in all of them when compared to normal hemoglobin at pH 7. This shows that the breakage of the Bohr group salt bridges by increasing pH or specific modification changes KT. Hence the Bohr group salt bridges break on ligation of the T state and are partially responsible for the free energy of cooperativity."}
{"id": "PMID:26417", "title": "Effect of temperature on fluorescence and circular dichroism of Escherichia coli dihydrofolate reductase and its complexes.", "content": "Dihydrofolate reductase and its complexes have been studied by fluorescence and circular dichroism. NADPH, trimethoprim, pyrimethamine, or Methotrexate binding causes small changes in the enzyme far ultraviolet CD which possibly arise from alterations in polypeptide backbone of the enzyme; however, their effects on enzyme far ultraviolet CD are also explained as the result of ligand interactions with enzyme aromatic groups. In ternary complexes of the enzyme, fluorescence properties of bound NADPH are surprisingly sensitive to the type of inhibitor bound nearby. The effect of temperature on the enzyme and its complexes is clearly shown by changes in enzyme fluorescence and CD. At temperatures near 45 degrees C, the enzyme undergoes an irreversible denaturation, as shown by major alterations in enzyme far ultraviolet CD and by an increased rate of fluorescence quenching. Binary complexes with NADPH or Methotrexate stabilize the enzyme towards this heat denaturation, whereas bound trimethoprim and pyrimethamine do not. Ternary complexes with NADPH and any of the ligands are more stable than the enzyme itself toward heat denaturation. Fluorescence-temperature and fluorescence polarization studies show that near 30 degrees C the enzyme undergoes a reversible transition that is modified by NADPH or methotrexate.", "contents": "Effect of temperature on fluorescence and circular dichroism of Escherichia coli dihydrofolate reductase and its complexes. Dihydrofolate reductase and its complexes have been studied by fluorescence and circular dichroism. NADPH, trimethoprim, pyrimethamine, or Methotrexate binding causes small changes in the enzyme far ultraviolet CD which possibly arise from alterations in polypeptide backbone of the enzyme; however, their effects on enzyme far ultraviolet CD are also explained as the result of ligand interactions with enzyme aromatic groups. In ternary complexes of the enzyme, fluorescence properties of bound NADPH are surprisingly sensitive to the type of inhibitor bound nearby. The effect of temperature on the enzyme and its complexes is clearly shown by changes in enzyme fluorescence and CD. At temperatures near 45 degrees C, the enzyme undergoes an irreversible denaturation, as shown by major alterations in enzyme far ultraviolet CD and by an increased rate of fluorescence quenching. Binary complexes with NADPH or Methotrexate stabilize the enzyme towards this heat denaturation, whereas bound trimethoprim and pyrimethamine do not. Ternary complexes with NADPH and any of the ligands are more stable than the enzyme itself toward heat denaturation. Fluorescence-temperature and fluorescence polarization studies show that near 30 degrees C the enzyme undergoes a reversible transition that is modified by NADPH or methotrexate."}
{"id": "PMID:26418", "title": "Proton NMR study of the thermodynamics and kinetics of the acid in equilibrium base transitions in reconstituted metmyoglobins.", "content": "Optical and proton NMR pH titrations of sperm whale metmyoglobin (metMb) in its native form and reconstituted with chemically modified hemes reveal that the pKa for the acid in equilibrium base transition decreases as the heme 2,4-substituents are made more electron withdrawing. The proton NMR spectra yields resonances which are averaged over the acidic and basic forms of the protein, but still exhibit significant exchange line broadening. Analysis of this exchange contribution to the linewidth is consistent with the simple kinetic scheme metMb+H2O + OH- k2 in equilibrium k1 metMbOH + H2O with k2 = 1.3 +/- 0.5 . 10(10) M-1 . s-1 and k1 = 1.6 +/- 0.6 . 10(5) s-1 for the native protein. The effect of electron-withdrawing substituents on the heme increase k2 and decrease k1.", "contents": "Proton NMR study of the thermodynamics and kinetics of the acid in equilibrium base transitions in reconstituted metmyoglobins. Optical and proton NMR pH titrations of sperm whale metmyoglobin (metMb) in its native form and reconstituted with chemically modified hemes reveal that the pKa for the acid in equilibrium base transition decreases as the heme 2,4-substituents are made more electron withdrawing. The proton NMR spectra yields resonances which are averaged over the acidic and basic forms of the protein, but still exhibit significant exchange line broadening. Analysis of this exchange contribution to the linewidth is consistent with the simple kinetic scheme metMb+H2O + OH- k2 in equilibrium k1 metMbOH + H2O with k2 = 1.3 +/- 0.5 . 10(10) M-1 . s-1 and k1 = 1.6 +/- 0.6 . 10(5) s-1 for the native protein. The effect of electron-withdrawing substituents on the heme increase k2 and decrease k1."}
{"id": "PMID:26419", "title": "The fluctuation of various enzyme activities due to myo-inositol deficiency in Saccharomyces carlsbergensis.", "content": "The neutral lipid accumulation in myo-inositol deficient Saccharomyces carlsbergensis results at least partly from an enhancement of acetyl CoA carboxylase activity due to the high level of fructose 1,6-biphosphate which activates acetyl CoA carboxylase, and due to the low level of citrate which counteracts the activation [4]. In an attempt to explore the effect of myo-inositol deficiency on the metabolic fluxes, various enzyme activities were compared between the myo-inositol supplemented and deficient cells. The activities of phosphofructokinase and ATP-citrate lyase increased by 74 and 83%, respectively. The activity of glucose-6-phosphate dehydrogenase was unchanged. Unlike acetyl CoA carboxylase, elimination of low molecular effectors had no influence on their activities. The thermostability of phosphofructokinase (at 53 degrees C) increased, while that of aldolase (at 48 degrees C) greatly decreased due to the deficiency. The thermostability of glucose-6-phosphate dehydrogenase (at 52 degrees C) was also unchanged.", "contents": "The fluctuation of various enzyme activities due to myo-inositol deficiency in Saccharomyces carlsbergensis. The neutral lipid accumulation in myo-inositol deficient Saccharomyces carlsbergensis results at least partly from an enhancement of acetyl CoA carboxylase activity due to the high level of fructose 1,6-biphosphate which activates acetyl CoA carboxylase, and due to the low level of citrate which counteracts the activation [4]. In an attempt to explore the effect of myo-inositol deficiency on the metabolic fluxes, various enzyme activities were compared between the myo-inositol supplemented and deficient cells. The activities of phosphofructokinase and ATP-citrate lyase increased by 74 and 83%, respectively. The activity of glucose-6-phosphate dehydrogenase was unchanged. Unlike acetyl CoA carboxylase, elimination of low molecular effectors had no influence on their activities. The thermostability of phosphofructokinase (at 53 degrees C) increased, while that of aldolase (at 48 degrees C) greatly decreased due to the deficiency. The thermostability of glucose-6-phosphate dehydrogenase (at 52 degrees C) was also unchanged."}
{"id": "PMID:26420", "title": "Effects of pH changes and charge characteristics in the uptake of norepinephrine by synaptosomes of rat brain.", "content": "The pH dependence of the initial uptake of norepinephrine by rat whole brain synaptosomes was studied using short incubation times at 37 degrees C in order to examine the possible involvement of the phenolic OH group. The pH vs. uptake profile exhibits a maximum near pH 8.2 in H2O medium. When the medium was changed to 2H2O, the profile showed a shift of maximum corresponding to the pKa change of the phenolic OH group. The pH vs. uptake profile of tyramine was quite different from that of norepinephrine. These pH effects on uptake were explained as manifestations of the involvement of the phenolic OH group in the process. The amine and phenolic hydroxyl groups in norepinephrine were studied separately by employing two series of compounds structurally related to catecholamines, amphetamine-like and catechol-like, for their inhibitory effects on the uptake. The inhibitions were affected by changes in pH with changes in opposite directions found for the two series indicating the need for a positive charge in the side chain and suggesting an effect of the negative charge on the ring. These charge characteristics agreed with the pH profile observed in uptake. Consequently, the two groups with opposite charge characteristics in norepinephrine both appear to function in the uptake process.", "contents": "Effects of pH changes and charge characteristics in the uptake of norepinephrine by synaptosomes of rat brain. The pH dependence of the initial uptake of norepinephrine by rat whole brain synaptosomes was studied using short incubation times at 37 degrees C in order to examine the possible involvement of the phenolic OH group. The pH vs. uptake profile exhibits a maximum near pH 8.2 in H2O medium. When the medium was changed to 2H2O, the profile showed a shift of maximum corresponding to the pKa change of the phenolic OH group. The pH vs. uptake profile of tyramine was quite different from that of norepinephrine. These pH effects on uptake were explained as manifestations of the involvement of the phenolic OH group in the process. The amine and phenolic hydroxyl groups in norepinephrine were studied separately by employing two series of compounds structurally related to catecholamines, amphetamine-like and catechol-like, for their inhibitory effects on the uptake. The inhibitions were affected by changes in pH with changes in opposite directions found for the two series indicating the need for a positive charge in the side chain and suggesting an effect of the negative charge on the ring. These charge characteristics agreed with the pH profile observed in uptake. Consequently, the two groups with opposite charge characteristics in norepinephrine both appear to function in the uptake process."}
{"id": "PMID:26421", "title": "Binding of polyanions to carrier ampholytes in isoelectric focusing.", "content": "The binding of carrier ampholytes to polyanions is markedly pH-dependent: it is very strong at pH 3, rather weak at pH 5 and abolished at pH 7. Binding is affected by the type of negative charge, its density and spatial orientation on the polyanion. On the basis of the type of negative charge, the binding strength decreases in the following order: polyphosphate greater than polysulphate greater than polycarboxylate. Given the same type of negative charge, the binding is dependent on charge density and its space orientation: thus polyglutamic acid forms stronger complexes than polygalacturonic acid. The minimum length of the polyanion eliciting a measurable binding appears to be of the order of about six negative charges, as demonstrated with hexametaphosphate.", "contents": "Binding of polyanions to carrier ampholytes in isoelectric focusing. The binding of carrier ampholytes to polyanions is markedly pH-dependent: it is very strong at pH 3, rather weak at pH 5 and abolished at pH 7. Binding is affected by the type of negative charge, its density and spatial orientation on the polyanion. On the basis of the type of negative charge, the binding strength decreases in the following order: polyphosphate greater than polysulphate greater than polycarboxylate. Given the same type of negative charge, the binding is dependent on charge density and its space orientation: thus polyglutamic acid forms stronger complexes than polygalacturonic acid. The minimum length of the polyanion eliciting a measurable binding appears to be of the order of about six negative charges, as demonstrated with hexametaphosphate."}
{"id": "PMID:26422", "title": "[Acetate kinase chromatography on agarose derivatives].", "content": "Acetate kinase from E. coli K-12 was studied chromatographically on omega-aminoalkyl polysacharide sorbents. The dependence of the protein sorption-desorption on ionic strength and the effect of pH on the acetate kinase sorption were studied. The increase in the ionic strength caused a decrease in the amount of protein sorbed on the hexamethylenediamine- and chlorotriasinehexamethylenediamine sepharoses. On hexamethylenediamine-, octamethylenediamine- and dimethylhexamethylenediamine agaroses acetate kinase was adsorbed within the pH range of 6.5-9.0, whereas on the chlorotriasinehexamethylenediamine sepharose--at pH 6.5-8.0. The active protein was eluted at ionic strength of 0.14-0.17 M. Acetate kinase was not adsorbed on the carboxypropyonylaminohexyl sepharose within the pH range studied, i.e. 5.0-9.0 and was not adsorbed on hexamethylenediamine agarose at pH 4.0 and on chlorotriasinehexamethylenediamine sepharose--at pH 9.0. The mechanism of the enzyme-adsorbent interaction is discussed.", "contents": "[Acetate kinase chromatography on agarose derivatives]. Acetate kinase from E. coli K-12 was studied chromatographically on omega-aminoalkyl polysacharide sorbents. The dependence of the protein sorption-desorption on ionic strength and the effect of pH on the acetate kinase sorption were studied. The increase in the ionic strength caused a decrease in the amount of protein sorbed on the hexamethylenediamine- and chlorotriasinehexamethylenediamine sepharoses. On hexamethylenediamine-, octamethylenediamine- and dimethylhexamethylenediamine agaroses acetate kinase was adsorbed within the pH range of 6.5-9.0, whereas on the chlorotriasinehexamethylenediamine sepharose--at pH 6.5-8.0. The active protein was eluted at ionic strength of 0.14-0.17 M. Acetate kinase was not adsorbed on the carboxypropyonylaminohexyl sepharose within the pH range studied, i.e. 5.0-9.0 and was not adsorbed on hexamethylenediamine agarose at pH 4.0 and on chlorotriasinehexamethylenediamine sepharose--at pH 9.0. The mechanism of the enzyme-adsorbent interaction is discussed."}
{"id": "PMID:26423", "title": "[Molecular weight and tertiary structure of transketolase from baker's yeast].", "content": "Molecular weight of native apotransketolase from baker's yeast is found to be 159000 +/- 6000 by means of sedimentation equilibrium and sedimentation-diffusion rate. The enzyme in a relatively low concentration reversibly dissociates into two subunits with molecular weight of about 80 000 at pH 7.6 and 20 degrees C. The equilibrium constant of the reaction monomer-dimer is 4.4 . 10(3) M-1. A decrease of the temperature stimulates the association of monomers into dimer, while the shift of pH 7.6 into acid or alkaline region stimulates the dissociation process. Dissociation becames irreversible at pH less than 5 and greater than 10.5.", "contents": "[Molecular weight and tertiary structure of transketolase from baker's yeast]. Molecular weight of native apotransketolase from baker's yeast is found to be 159000 +/- 6000 by means of sedimentation equilibrium and sedimentation-diffusion rate. The enzyme in a relatively low concentration reversibly dissociates into two subunits with molecular weight of about 80 000 at pH 7.6 and 20 degrees C. The equilibrium constant of the reaction monomer-dimer is 4.4 . 10(3) M-1. A decrease of the temperature stimulates the association of monomers into dimer, while the shift of pH 7.6 into acid or alkaline region stimulates the dissociation process. Dissociation becames irreversible at pH less than 5 and greater than 10.5."}
{"id": "PMID:26424", "title": "[Properties of the high energy phosphate bonds of triphosphoinositide].", "content": "High heat of enzymatic hydrolysis of triphosphoinositide phosphate bonds and of high-energy phosphates is observed using microcalorimetry. Heats of hydrolysis of triphosphoinositide, ADP and ATP sharply increase with increasing pH values from 6.6 to 7.4. Heat of hydrolysis of diphosphoinositide correlates with that of low-energy phosphates, pK4 and pK5 values for triphosphoinositide are found to be 7.4 and 9.3 respectively by means of potentiometric titration deltaGo' values for diphosphoinositide and triphosphoinositide are -3.5 and -7.1 kcal/mole respectively, taking into consideration the correction for heat neutralization-ionization during hydrolysis. Rapid triphosphoinositide hydrolysis takes place in 1% aqueous pyridine solution at 100 degrees C. In contrast to diphosphoinositide and monophosphoinositide, infrared spectra of triphosphoinositide have an additional absorption band at 930 cm(-1). 31P NMR method has revealed the presence of one diester and two monoester groups in the molecule of triphosphoinositide. The differences described between triphosphoinositide and other compounds with phosphomonoester groups are suggested to be due to electrostatic nonbounded interaction of vicinal diequatorial phosphate groups.", "contents": "[Properties of the high energy phosphate bonds of triphosphoinositide]. High heat of enzymatic hydrolysis of triphosphoinositide phosphate bonds and of high-energy phosphates is observed using microcalorimetry. Heats of hydrolysis of triphosphoinositide, ADP and ATP sharply increase with increasing pH values from 6.6 to 7.4. Heat of hydrolysis of diphosphoinositide correlates with that of low-energy phosphates, pK4 and pK5 values for triphosphoinositide are found to be 7.4 and 9.3 respectively by means of potentiometric titration deltaGo' values for diphosphoinositide and triphosphoinositide are -3.5 and -7.1 kcal/mole respectively, taking into consideration the correction for heat neutralization-ionization during hydrolysis. Rapid triphosphoinositide hydrolysis takes place in 1% aqueous pyridine solution at 100 degrees C. In contrast to diphosphoinositide and monophosphoinositide, infrared spectra of triphosphoinositide have an additional absorption band at 930 cm(-1). 31P NMR method has revealed the presence of one diester and two monoester groups in the molecule of triphosphoinositide. The differences described between triphosphoinositide and other compounds with phosphomonoester groups are suggested to be due to electrostatic nonbounded interaction of vicinal diequatorial phosphate groups."}
{"id": "PMID:26425", "title": "[Indirect immunoprecipitation by rat liver polyribosomes using antibodies to tyrosine aminotransferase].", "content": "A fraction of rat liver polyribosomes is isolated, which in its immunochemical characteristics considerably enriched with polyribosomes capable to synthesize hydrocortisone-induced liver tyrosine aminotransferase isoenzyme. This specific polyribosome fraction was purified by immunochemical fractionation of total liver polyribosomes using indirect precipitation. The content of polyribosomes in immunoprecipitates comprise 0.4-0.8% of its initial amount (before immunochemical fractionation). The ratio of specific polyribosomes in immunoprecipitates varies from 20 to 45%, which corresponds to 25-100-fold purification. The data obtained suggest that the method of indirect precipitation can be an efficient step in the isolation procedure of individual mRNA.", "contents": "[Indirect immunoprecipitation by rat liver polyribosomes using antibodies to tyrosine aminotransferase]. A fraction of rat liver polyribosomes is isolated, which in its immunochemical characteristics considerably enriched with polyribosomes capable to synthesize hydrocortisone-induced liver tyrosine aminotransferase isoenzyme. This specific polyribosome fraction was purified by immunochemical fractionation of total liver polyribosomes using indirect precipitation. The content of polyribosomes in immunoprecipitates comprise 0.4-0.8% of its initial amount (before immunochemical fractionation). The ratio of specific polyribosomes in immunoprecipitates varies from 20 to 45%, which corresponds to 25-100-fold purification. The data obtained suggest that the method of indirect precipitation can be an efficient step in the isolation procedure of individual mRNA."}
{"id": "PMID:26426", "title": "[Light activation of NADH and NADPH].", "content": "Illumination of NADH and NADPH by UV-light in the absence of oxygen resulted in the reduction of ferredoxin or methyl-viologen to cation-radical and under prolonged illumination to dihydrodipyridyl. The reaction may by accompanied by triplet and singlet exitation of NADH. It was shown that hematoporphyrin in aqueous solution photosensitized the reaction of NADH oxidation by ferredoxin and methylviologen to the visible region of the spectrum. Under light excitation the redox potentials of NADH and NADPH were increased up to the level exceeding the potential of hydrogen electrode. Illumination of NADH and NADPH by UV-light in the presence of bacterial hydrogenase resulted in hydrogen evolution. The reaction of hydrogen evolution could be sensitised towards the visible region of the spectrum by chlorophyll or chloroplasts.", "contents": "[Light activation of NADH and NADPH]. Illumination of NADH and NADPH by UV-light in the absence of oxygen resulted in the reduction of ferredoxin or methyl-viologen to cation-radical and under prolonged illumination to dihydrodipyridyl. The reaction may by accompanied by triplet and singlet exitation of NADH. It was shown that hematoporphyrin in aqueous solution photosensitized the reaction of NADH oxidation by ferredoxin and methylviologen to the visible region of the spectrum. Under light excitation the redox potentials of NADH and NADPH were increased up to the level exceeding the potential of hydrogen electrode. Illumination of NADH and NADPH by UV-light in the presence of bacterial hydrogenase resulted in hydrogen evolution. The reaction of hydrogen evolution could be sensitised towards the visible region of the spectrum by chlorophyll or chloroplasts."}
{"id": "PMID:26427", "title": "[Ribosomal proteins of pea seeds behaving like anions at pH 8.6].", "content": "A group of proteins migrating to the anode at pH 8.6 under polyacrylamide gel electrophoresis was revealed in the total protein of non-dissociated KCl-washed pea seed ribosomes. No proteins with an isoelectric point below pH 4.2 Were found. The presence of acidic proteins in 80 S ribosomes is due to the presence of a specific set of relatively acidic proteins in the total protein of large (5 major and 10 minor components) and small (2 major and 4 minor components) subunits. The mostly acidic proteins are located in the large subunit. The acidic proteins of 60S and 40S subunits are represented by the polypeptide chains with molecular weights from 48 000 to 13 000. The acidic proteins are present in the ribosomes studied in considerably less number than the basic proteins, and the former produce a very weak staining under electrophoretic analysis as compared with the latter. The data obtained suggest that 80S ribosomes of higher plants differ from animal ribosomes by a higher content of relatively acidic proteins.", "contents": "[Ribosomal proteins of pea seeds behaving like anions at pH 8.6]. A group of proteins migrating to the anode at pH 8.6 under polyacrylamide gel electrophoresis was revealed in the total protein of non-dissociated KCl-washed pea seed ribosomes. No proteins with an isoelectric point below pH 4.2 Were found. The presence of acidic proteins in 80 S ribosomes is due to the presence of a specific set of relatively acidic proteins in the total protein of large (5 major and 10 minor components) and small (2 major and 4 minor components) subunits. The mostly acidic proteins are located in the large subunit. The acidic proteins of 60S and 40S subunits are represented by the polypeptide chains with molecular weights from 48 000 to 13 000. The acidic proteins are present in the ribosomes studied in considerably less number than the basic proteins, and the former produce a very weak staining under electrophoretic analysis as compared with the latter. The data obtained suggest that 80S ribosomes of higher plants differ from animal ribosomes by a higher content of relatively acidic proteins."}
{"id": "PMID:26428", "title": "[Effect of N-alkylimidazoles on oxidation of o-dianizidine catalyzed by horseradish peroxidase].", "content": "Effect of a number of N-alkylimidazoles (from N-methyl to N-octylimidazole) on peroxidase oxidation of o-dianizidine at pH 8.0 is studied. Alkylimidazoles studied are found to activate the reaction under given conditions, the activation type being non-competitive KA and (alpha) values are similar for all the activators, which suggests a similar mechanism of their action. Similar KA values suppose an insignificant role of hydrophobic interactions in the binding of N-alkylimidazoles with the enzyme.", "contents": "[Effect of N-alkylimidazoles on oxidation of o-dianizidine catalyzed by horseradish peroxidase]. Effect of a number of N-alkylimidazoles (from N-methyl to N-octylimidazole) on peroxidase oxidation of o-dianizidine at pH 8.0 is studied. Alkylimidazoles studied are found to activate the reaction under given conditions, the activation type being non-competitive KA and (alpha) values are similar for all the activators, which suggests a similar mechanism of their action. Similar KA values suppose an insignificant role of hydrophobic interactions in the binding of N-alkylimidazoles with the enzyme."}
{"id": "PMID:26429", "title": "[Interaction of intracellular RNAase from Aspergillus clavatus with derivatives of its substrates].", "content": "Using spectrophotometric and kinetic methods and also the methods of protection of Aspergillus clavatus RNAse (EC 3.1.4.23) by adenine nucleotides and their components against inactivation by means of acylation or heating, it was found that RNAse-nucleotide complex was formed by association of one enzyme molecule with one nucleotide molecule. It was also shown that all components of nucleotides (base, ribose and phosphate) take part in the formation of such complex and the removal of one of them (base or phosphate) lead to loosening of bindings of remaining fragments (ribose-5'-monophosphate, adenine) with the active site of RNAse, and to disappearance of bends within the pH range of 3.0-4.0 on the plot of pKi (5'-MP) versus pH, within the pH range of 5.5-7.0 on the plot of oKi (Ado) versus pH. The possibility of participation of associative pair RNAse imidasole groups - nucleotide phosphate groups and RNAse carboxylic group - nucleotide base in the mechanism of formation of enzyme-nucleotide (enzyme-substrate) complexes is postulated.", "contents": "[Interaction of intracellular RNAase from Aspergillus clavatus with derivatives of its substrates]. Using spectrophotometric and kinetic methods and also the methods of protection of Aspergillus clavatus RNAse (EC 3.1.4.23) by adenine nucleotides and their components against inactivation by means of acylation or heating, it was found that RNAse-nucleotide complex was formed by association of one enzyme molecule with one nucleotide molecule. It was also shown that all components of nucleotides (base, ribose and phosphate) take part in the formation of such complex and the removal of one of them (base or phosphate) lead to loosening of bindings of remaining fragments (ribose-5'-monophosphate, adenine) with the active site of RNAse, and to disappearance of bends within the pH range of 3.0-4.0 on the plot of pKi (5'-MP) versus pH, within the pH range of 5.5-7.0 on the plot of oKi (Ado) versus pH. The possibility of participation of associative pair RNAse imidasole groups - nucleotide phosphate groups and RNAse carboxylic group - nucleotide base in the mechanism of formation of enzyme-nucleotide (enzyme-substrate) complexes is postulated."}
{"id": "PMID:26430", "title": "[Subcellular distribution and several properties of the cAMP enzyme system of phototrophic bacteria].", "content": "In the cells of the phototrophic bacteria Rhodospirillum rubrum and Rhodopseudomonas palustris the two enzymes of the cAMP system enzymes - adenylate cyclase and cAMP phosphodiesterase (PDE) exist in a soluble and membrane-bound forms. After mild disruption of the cells (sonication up to 3 min) the activity of both enzymes is found in the chromatophores. In the cells of the two types of bacteria grown under anaerobic conditions soluble adenylate cyclase is predominant. In the cells of R. rubrum the soluble form of PDE posesses higher activity, whereas in the cells of Rh. palustris a higher activity is observed in the membrane-bound form. In addition to their different localization in the cells, the PDE forms of Rh. rubrum differ in their ratios to the concentrations of hydrogen ions and bivalent metals; the latter difference, however, may be accounted for by the effect of a protein modulator of PDE. The pH optimum of membrane-bound PDE is 9.15. Soluble PDE has two activity maxima at pH 7.5 and 8.7. It is probable that similar to the animal tissue enzyme, PDE from Rh. rubrum exists in the soluble phase in at least tw forms. Close pH optima for soluble adenylate cyclase and for one of the soluble PDE forms (about 8.5) may indicate the unidirectional control of these enzymes by hydrogen ion concentration.", "contents": "[Subcellular distribution and several properties of the cAMP enzyme system of phototrophic bacteria]. In the cells of the phototrophic bacteria Rhodospirillum rubrum and Rhodopseudomonas palustris the two enzymes of the cAMP system enzymes - adenylate cyclase and cAMP phosphodiesterase (PDE) exist in a soluble and membrane-bound forms. After mild disruption of the cells (sonication up to 3 min) the activity of both enzymes is found in the chromatophores. In the cells of the two types of bacteria grown under anaerobic conditions soluble adenylate cyclase is predominant. In the cells of R. rubrum the soluble form of PDE posesses higher activity, whereas in the cells of Rh. palustris a higher activity is observed in the membrane-bound form. In addition to their different localization in the cells, the PDE forms of Rh. rubrum differ in their ratios to the concentrations of hydrogen ions and bivalent metals; the latter difference, however, may be accounted for by the effect of a protein modulator of PDE. The pH optimum of membrane-bound PDE is 9.15. Soluble PDE has two activity maxima at pH 7.5 and 8.7. It is probable that similar to the animal tissue enzyme, PDE from Rh. rubrum exists in the soluble phase in at least tw forms. Close pH optima for soluble adenylate cyclase and for one of the soluble PDE forms (about 8.5) may indicate the unidirectional control of these enzymes by hydrogen ion concentration."}
{"id": "PMID:26431", "title": "[Irreversible inactivation of Chlorella glutamine synthetase by urea].", "content": "The effect of urea on Chlorella glutamine synthetase (E. C. 6.3.1.2) activity and tertiary structure is investigated. Urea is found to inhibit the activity of glutamine synthetase, the inhibitory effect being independent on the time. The enzyme molecule relax and changes its affinity to ammonium under the effect of urea at concentrations of 1.0-4.0 M. Higher concentrations of urea (5,0 M and more) produce a dissociation of the enzyme molecule into monomers without any intermediate forms. Monomers do not possess any synthetase and transferase activities. Substrates and cofactors do not protect the enzyme from the effect of urea and do not stimulate the emzyme reactivation and reaggregation after its dissotiation. The data obtained are discussed from the viewpoint of the regulation of Chlorella glutamine synthetase activity in vivo.", "contents": "[Irreversible inactivation of Chlorella glutamine synthetase by urea]. The effect of urea on Chlorella glutamine synthetase (E. C. 6.3.1.2) activity and tertiary structure is investigated. Urea is found to inhibit the activity of glutamine synthetase, the inhibitory effect being independent on the time. The enzyme molecule relax and changes its affinity to ammonium under the effect of urea at concentrations of 1.0-4.0 M. Higher concentrations of urea (5,0 M and more) produce a dissociation of the enzyme molecule into monomers without any intermediate forms. Monomers do not possess any synthetase and transferase activities. Substrates and cofactors do not protect the enzyme from the effect of urea and do not stimulate the emzyme reactivation and reaggregation after its dissotiation. The data obtained are discussed from the viewpoint of the regulation of Chlorella glutamine synthetase activity in vivo."}
{"id": "PMID:26432", "title": "Influence of pH and temperature on behaviour of surfactant from human neonatal lungs.", "content": "The surface pressures of human surfactant films were measured under static conditions and under dynamic (expansion-compression) conditions. The results from both methods showed that the maximum surface pressures generated by surfactant films in vitro were strongly dependent on temperature throughout the range 29-41 degrees C, higher pressures being achieved at the lower temperatures. In contrast, increasing the pH of the subphase stepwise over the range 7.1-7.7 produced a modest fall in the maximum pressures exerted by the films. The possibility that surfactant films may behave in a similar manner in vivo is discussed.", "contents": "Influence of pH and temperature on behaviour of surfactant from human neonatal lungs. The surface pressures of human surfactant films were measured under static conditions and under dynamic (expansion-compression) conditions. The results from both methods showed that the maximum surface pressures generated by surfactant films in vitro were strongly dependent on temperature throughout the range 29-41 degrees C, higher pressures being achieved at the lower temperatures. In contrast, increasing the pH of the subphase stepwise over the range 7.1-7.7 produced a modest fall in the maximum pressures exerted by the films. The possibility that surfactant films may behave in a similar manner in vivo is discussed."}
{"id": "PMID:26433", "title": "In vitro effects of inosine-pyruvate-phosphate on P50 values and DPG contents of fresh and stored blood from healthy neonates, symptom-free premature infants and premature infants with respiratory distress syndrome.", "content": "A study was made of the effect of a 3-hour incubation with inosine-pyruvate-phosphate (IPP) on the P50 values and 2,3-DPG contents of fresh blood and blood which had stood for 96 h, from healthy adults, term neonates, 1-2-week-old symptom-free premature infants and RDS premature infants. It was found that the P50 value and the 2,3-DPG content could be increased considerably by IPP treatment in both the fresh and the stood blood in the various groups of neonates. The question remains open as to whether the effect of IPP, in significantly improving the O2 transport in neonates, is a consequence of the 2,3-DPG alone or of some other metabolite. In RDS the stimulating effect of the IPP mixture is appreciably lower.", "contents": "In vitro effects of inosine-pyruvate-phosphate on P50 values and DPG contents of fresh and stored blood from healthy neonates, symptom-free premature infants and premature infants with respiratory distress syndrome. A study was made of the effect of a 3-hour incubation with inosine-pyruvate-phosphate (IPP) on the P50 values and 2,3-DPG contents of fresh blood and blood which had stood for 96 h, from healthy adults, term neonates, 1-2-week-old symptom-free premature infants and RDS premature infants. It was found that the P50 value and the 2,3-DPG content could be increased considerably by IPP treatment in both the fresh and the stood blood in the various groups of neonates. The question remains open as to whether the effect of IPP, in significantly improving the O2 transport in neonates, is a consequence of the 2,3-DPG alone or of some other metabolite. In RDS the stimulating effect of the IPP mixture is appreciably lower."}
{"id": "PMID:26436", "title": "[Effect of heparin polyanion on chromatin preparations obtained in solutions of low ionic strength].", "content": "DNP obtained in low ionic strength solutions (0.7 mM Na-phosphate buffer, pH 7.0) was found to be dissociated under the effect of heparin. The dissociation order of the three histone fractions was established: H2a, H1, H4. The following order of histones is assumed: H2a, H2b, H1, H3, H4. Activation of the DNA and RNA synthesis in the eucaryotic cells, their nuclei and chromatin under the effect of low heparin doses should be associated not with the H1 histone dissociation, but with the dissociation of histones moderately rich in lysine--H2a, and, probably, H2b.", "contents": "[Effect of heparin polyanion on chromatin preparations obtained in solutions of low ionic strength]. DNP obtained in low ionic strength solutions (0.7 mM Na-phosphate buffer, pH 7.0) was found to be dissociated under the effect of heparin. The dissociation order of the three histone fractions was established: H2a, H1, H4. The following order of histones is assumed: H2a, H2b, H1, H3, H4. Activation of the DNA and RNA synthesis in the eucaryotic cells, their nuclei and chromatin under the effect of low heparin doses should be associated not with the H1 histone dissociation, but with the dissociation of histones moderately rich in lysine--H2a, and, probably, H2b."}
{"id": "PMID:26437", "title": "[Property of a heat- and acid-stable inhibitor of serine proteinases from the blood serum to inhibit lymphcyte transformation stimulated by mitogens].", "content": "Thermo- and acid-stable serine proteases inhibitor from the rabbit blood serum (TASPI) was shown to inhibit the human peripheral blood lymphocytes transformation stimulated by phytohemagglutinin (PHA) or concanavalin A. The extent of inhibition depended on the concentration of the preparation and its specific activity. The maximal inhibition of lymphocytes proliferation constituted 50 to 70%. TASPI displayed no cytotoxic activity. Considerably more effective inhibition was demonstrated by TASPI addition to the culture medium 24 hours after the addition of PHA. The antiprotease activity of crude human serum and that inactivated under different conditions is described. The results obtained suggest the participation of TASPI in the control of biological activity of the lymphoid tissue cells.", "contents": "[Property of a heat- and acid-stable inhibitor of serine proteinases from the blood serum to inhibit lymphcyte transformation stimulated by mitogens]. Thermo- and acid-stable serine proteases inhibitor from the rabbit blood serum (TASPI) was shown to inhibit the human peripheral blood lymphocytes transformation stimulated by phytohemagglutinin (PHA) or concanavalin A. The extent of inhibition depended on the concentration of the preparation and its specific activity. The maximal inhibition of lymphocytes proliferation constituted 50 to 70%. TASPI displayed no cytotoxic activity. Considerably more effective inhibition was demonstrated by TASPI addition to the culture medium 24 hours after the addition of PHA. The antiprotease activity of crude human serum and that inactivated under different conditions is described. The results obtained suggest the participation of TASPI in the control of biological activity of the lymphoid tissue cells."}
{"id": "PMID:26443", "title": "Effects of oxypertine on the isolated vas deferens of the rat.", "content": "1 The isolated vas deferens of the rat was used to examine the peripheral action of oxypertine, a psychotropic-anxiolytic drug. 2 Oxypertine (4.4 X 10(-10) M to 2.6 X 10(-5) M) antagonized competitively the effects of noradrenaline (pA2 = 7.2), 5-hydroxytryptamine (pA2 = 8.6) and dopamine (pA2 = 9.8). 3 Oxypertine (8.8 X 10(-9) M to 2.6 X 10(-5) M) antagonized the effects of low concentrations of acetylcholine and enhanced the contractions elicited by high concentrations of acetylcholine. 4 The contractions evoked by transmural stimulation of the vas deferens were reduced by oxypertine. 5 Oxypertine failed to antagonize the responses to potassium chloride. 6 These findings are compared with the effects of other antidepressant drugs.", "contents": "Effects of oxypertine on the isolated vas deferens of the rat. 1 The isolated vas deferens of the rat was used to examine the peripheral action of oxypertine, a psychotropic-anxiolytic drug. 2 Oxypertine (4.4 X 10(-10) M to 2.6 X 10(-5) M) antagonized competitively the effects of noradrenaline (pA2 = 7.2), 5-hydroxytryptamine (pA2 = 8.6) and dopamine (pA2 = 9.8). 3 Oxypertine (8.8 X 10(-9) M to 2.6 X 10(-5) M) antagonized the effects of low concentrations of acetylcholine and enhanced the contractions elicited by high concentrations of acetylcholine. 4 The contractions evoked by transmural stimulation of the vas deferens were reduced by oxypertine. 5 Oxypertine failed to antagonize the responses to potassium chloride. 6 These findings are compared with the effects of other antidepressant drugs."}
{"id": "PMID:26444", "title": "Investigation of the role of histamine in antigen-induced bronchoconstriction in the ascaris-hypersensitive dog.", "content": "1 Aerosol administration of ascaris antigen to the airways of ascaris-hypersensitive dogs provoked increases in pulmonary resistance (Rp) and decreases in dynamic lung compliance (Cdyn). These changes in pulmonary mechanics were not inhibited by the histamine H1-receptor antagonists, diphenhydramine or mepyramine. 2 Increases in Rp and decreases in Cdyn induced by a histamine aerosol were markedly or totally inhibited by comparable doses of these H1-antihistamines. 3 Doses of antigen which produced pathophysiological pulmonary responses failed to produce a detectable histamine release from the cardiopulmonary system in vivo. Aerosol antigen provocation, equivalent to 5 to 9 times greater than that which produced substantial pathophysiological pulmonary responses, did cause histamine release in vivo. 4 The canine cardiopulmonary system showed only a modest ability to remove and/or degrade circulating histamine. 5 It is concluded that histamine may not play a major role in mediating the acute antigen-induced bronchoconstriction in the ascaris-hypersensitive dog.", "contents": "Investigation of the role of histamine in antigen-induced bronchoconstriction in the ascaris-hypersensitive dog. 1 Aerosol administration of ascaris antigen to the airways of ascaris-hypersensitive dogs provoked increases in pulmonary resistance (Rp) and decreases in dynamic lung compliance (Cdyn). These changes in pulmonary mechanics were not inhibited by the histamine H1-receptor antagonists, diphenhydramine or mepyramine. 2 Increases in Rp and decreases in Cdyn induced by a histamine aerosol were markedly or totally inhibited by comparable doses of these H1-antihistamines. 3 Doses of antigen which produced pathophysiological pulmonary responses failed to produce a detectable histamine release from the cardiopulmonary system in vivo. Aerosol antigen provocation, equivalent to 5 to 9 times greater than that which produced substantial pathophysiological pulmonary responses, did cause histamine release in vivo. 4 The canine cardiopulmonary system showed only a modest ability to remove and/or degrade circulating histamine. 5 It is concluded that histamine may not play a major role in mediating the acute antigen-induced bronchoconstriction in the ascaris-hypersensitive dog."}
{"id": "PMID:26445", "title": "Characterization of receptors mediating 5-hydroxytryptamine- and catecholamine-induced platelet aggregation, assessed by the actions of alpha- and beta-blockers, butyrophenones, 5-HT antagonists and chlorpromazine.", "content": "1 Blood platelets from normal human volunteers were isolated and aggregated in vitro with 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine and N-dimethyldopamine (DMDA). 2 The effects of 5-HT antagonists, alpha- and beta-adrenoceptor blocking agents, butyrophenones and chlorpromazine upon aggregation induced by the four amines were investigated. 3 Only the the 5-HT antagonists, chlorpromazine and spiroperidol were potent inhibitors of 5-HT-induced aggregation, and only phentolamine was a potent inhibitor of the catecholamine-induced aggregation. 4 Evidence was obtained for two populations of receptors, one for 5-HT and one for the three catecholamines.", "contents": "Characterization of receptors mediating 5-hydroxytryptamine- and catecholamine-induced platelet aggregation, assessed by the actions of alpha- and beta-blockers, butyrophenones, 5-HT antagonists and chlorpromazine. 1 Blood platelets from normal human volunteers were isolated and aggregated in vitro with 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine and N-dimethyldopamine (DMDA). 2 The effects of 5-HT antagonists, alpha- and beta-adrenoceptor blocking agents, butyrophenones and chlorpromazine upon aggregation induced by the four amines were investigated. 3 Only the the 5-HT antagonists, chlorpromazine and spiroperidol were potent inhibitors of 5-HT-induced aggregation, and only phentolamine was a potent inhibitor of the catecholamine-induced aggregation. 4 Evidence was obtained for two populations of receptors, one for 5-HT and one for the three catecholamines."}
{"id": "PMID:26446", "title": "Biochemical evidence for the dual action of labetalol on alpha- and beta-adrenoceptors.", "content": "1 Labetalol (AH 5158A) inhibited the adrenaline-stimulated adenylate cyclase activity of rat liver and heart. This drug had no effect on basal or guanosine triphosphate (GTP)-activated adenylate cyclase activities. 2 Labetalol displaced the binding of the specific ligands [3H]-dihydroergocryptine and (-)-[3H]-dihydroalprenolol from their respective alpha and beta-adrenoceptors in rat heart and liver. The affinity of labetalol was 10 fold higher for the beta- than for the alpha-adrenoceptor. It appeared to be 10 to 100 times less potent than phentolamine in blocking alpha-adrenoceptors and 5 to 10 times less potent than propranolol in blocking beta-receptors. 3 It is concluded that labetalol exerts its dual alpha- and beta-antagonism by acting directly on the plasma membranes, where it binds competitively to alpha- and beta-adrenoceptors.", "contents": "Biochemical evidence for the dual action of labetalol on alpha- and beta-adrenoceptors. 1 Labetalol (AH 5158A) inhibited the adrenaline-stimulated adenylate cyclase activity of rat liver and heart. This drug had no effect on basal or guanosine triphosphate (GTP)-activated adenylate cyclase activities. 2 Labetalol displaced the binding of the specific ligands [3H]-dihydroergocryptine and (-)-[3H]-dihydroalprenolol from their respective alpha and beta-adrenoceptors in rat heart and liver. The affinity of labetalol was 10 fold higher for the beta- than for the alpha-adrenoceptor. It appeared to be 10 to 100 times less potent than phentolamine in blocking alpha-adrenoceptors and 5 to 10 times less potent than propranolol in blocking beta-receptors. 3 It is concluded that labetalol exerts its dual alpha- and beta-antagonism by acting directly on the plasma membranes, where it binds competitively to alpha- and beta-adrenoceptors."}
{"id": "PMID:26447", "title": "The treatment of frigidity: a comparative study of group and individual desensitization.", "content": "Forty patients took part in this study. Twenty patients treated by group desensitization were compared with twenty treated by individual desensitization. Group desensitization appeared the more effective treatment if outcome was measured on the patients' self-rating scale, but the less effective if outcome was measured by the sexual interest questionnaire. Of the two, the group method took longer to administer, but more patients treated in this way completed the course of treatment.", "contents": "The treatment of frigidity: a comparative study of group and individual desensitization. Forty patients took part in this study. Twenty patients treated by group desensitization were compared with twenty treated by individual desensitization. Group desensitization appeared the more effective treatment if outcome was measured on the patients' self-rating scale, but the less effective if outcome was measured by the sexual interest questionnaire. Of the two, the group method took longer to administer, but more patients treated in this way completed the course of treatment."}
{"id": "PMID:26450", "title": "Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. Report of a study group on bacterial resistance.", "content": "Twenty laboratories in England and Scotland took part in 1977 in a survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. In Str pneumoniae 59 (6.8%) of the 866 strains studied were resistant to tetracycline and three to chloramphenicol, and one strain showed a decreased susceptibility to penicillin. The prevalence of resistance to tetracycline was lower than that found in a similar study performed in 1975. Nine hundred and fifty-two strains of H influenzae were examined: 15 (1.6%) were resistant to ampicillin (all were beta-lactamase producers) and 26 (2.7%) to tetracycline. Only two strains were resistant to chloramphenicol and two to trimethoprim. Sixty-three H influenzae strains were capsulated. Thirty-four of these were of Pittman type b, and antibiotic resistance, particularly to ampicillin, was more common in these than in other serotypes or non-typable strains. Some variation was seen in the resistance rate of both H influenzae and Str pneumoniae to tetracycline in strains from different centres, but too few were isolated to assess whether this represented a true geographical difference.", "contents": "Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. Report of a study group on bacterial resistance. Twenty laboratories in England and Scotland took part in 1977 in a survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. In Str pneumoniae 59 (6.8%) of the 866 strains studied were resistant to tetracycline and three to chloramphenicol, and one strain showed a decreased susceptibility to penicillin. The prevalence of resistance to tetracycline was lower than that found in a similar study performed in 1975. Nine hundred and fifty-two strains of H influenzae were examined: 15 (1.6%) were resistant to ampicillin (all were beta-lactamase producers) and 26 (2.7%) to tetracycline. Only two strains were resistant to chloramphenicol and two to trimethoprim. Sixty-three H influenzae strains were capsulated. Thirty-four of these were of Pittman type b, and antibiotic resistance, particularly to ampicillin, was more common in these than in other serotypes or non-typable strains. Some variation was seen in the resistance rate of both H influenzae and Str pneumoniae to tetracycline in strains from different centres, but too few were isolated to assess whether this represented a true geographical difference."}
{"id": "PMID:26452", "title": "Recurrent genital candidosis in women and the effect of intermittent prophylactic treatment.", "content": "A study of clotrimazole for the treatment of recurrent genital candidosis unexpectedly showed that symptoms and infection can be dissociated. The aim of the study was to see if intermittent antifungal treatment would reduce symptoms in women constantly distressed by recurrent genital candidosis. Forty women seriously affected by the condition were initially given oral and local antifungal treatment. When the patients were symptom-free and the vagina was free of yeasts, they were entered into a double-blind clinical trial and were treated prophylactically for four months with either intermittent clotrimazole pessaries and cream or a placebo. The prophylactic treatment kept symptoms below a critical level but did not affect the return of the yeasts to the vagina. This dissociation between symptoms and vaginal yeasts was unexpected. Rectal yeast carriage was unaffected by prophylactic vaginal treatment. Male contacts and patients both showed a high incidence of non-specific genital infection. This association has seldom been reported. A few patients cultured yeasts from their homes but this environment was not considered a major source of reinfection. The vaginal pH did not appear to be altered by the presence of yeasts. The results of the study suggested that symptoms in women with recurrent genital candidosis were not caused by yeasts alone, and possibly the reason for recurrences might lie not in constant reinfection by yeasts, but in failure to recognise and remove a primary underlying factor, perhaps infection with other sexually transmitted agents. The question of a synergistic action between yeasts and other organisms is discussed.", "contents": "Recurrent genital candidosis in women and the effect of intermittent prophylactic treatment. A study of clotrimazole for the treatment of recurrent genital candidosis unexpectedly showed that symptoms and infection can be dissociated. The aim of the study was to see if intermittent antifungal treatment would reduce symptoms in women constantly distressed by recurrent genital candidosis. Forty women seriously affected by the condition were initially given oral and local antifungal treatment. When the patients were symptom-free and the vagina was free of yeasts, they were entered into a double-blind clinical trial and were treated prophylactically for four months with either intermittent clotrimazole pessaries and cream or a placebo. The prophylactic treatment kept symptoms below a critical level but did not affect the return of the yeasts to the vagina. This dissociation between symptoms and vaginal yeasts was unexpected. Rectal yeast carriage was unaffected by prophylactic vaginal treatment. Male contacts and patients both showed a high incidence of non-specific genital infection. This association has seldom been reported. A few patients cultured yeasts from their homes but this environment was not considered a major source of reinfection. The vaginal pH did not appear to be altered by the presence of yeasts. The results of the study suggested that symptoms in women with recurrent genital candidosis were not caused by yeasts alone, and possibly the reason for recurrences might lie not in constant reinfection by yeasts, but in failure to recognise and remove a primary underlying factor, perhaps infection with other sexually transmitted agents. The question of a synergistic action between yeasts and other organisms is discussed."}
{"id": "PMID:26455", "title": "[Nycthemeral plasma and testicular androgen contents in guinea pigs at puberty].", "content": "A study based upon transversal sampling involving 13 series of 7 animals each does not show a significant circadian rhythm of testosterone and delta4 androstenedione concentrations in the plasma and testis of the guinea-pig at the age of puberty.", "contents": "[Nycthemeral plasma and testicular androgen contents in guinea pigs at puberty]. A study based upon transversal sampling involving 13 series of 7 animals each does not show a significant circadian rhythm of testosterone and delta4 androstenedione concentrations in the plasma and testis of the guinea-pig at the age of puberty."}
{"id": "PMID:26456", "title": "Energy-driven uptake of humic acids by Aspergillus niger.", "content": "The uptake of humic acids by mycelia of Aspergillus niger was demonstrated to be energy-dependent with a sensitivity to sodium azide and to 2,4-dinitrophenol. Greater uptake of humic acids by submerged mycelium occurred at pH 3.0 and at 32 degrees C. The rate of uptake was influenced by the concentration of humic acids with an apparent Km of 0.2 grams/ml and with a Vmax of 0.13 mg humic acids per gram mycelial dry weight.10 min-1. In the absence of added energy source, Vmax of 0.05 mg humic acids per gram mycelial dry wt.10 min-1 was obtained; however, the affinity for humic acids by this uptake system was the same as for the energy-driven process. Apparent binding of humic acids to cell structures was indicated because only 41.8% of the humic acids taken up by the energy-dependent system could be recovered.", "contents": "Energy-driven uptake of humic acids by Aspergillus niger. The uptake of humic acids by mycelia of Aspergillus niger was demonstrated to be energy-dependent with a sensitivity to sodium azide and to 2,4-dinitrophenol. Greater uptake of humic acids by submerged mycelium occurred at pH 3.0 and at 32 degrees C. The rate of uptake was influenced by the concentration of humic acids with an apparent Km of 0.2 grams/ml and with a Vmax of 0.13 mg humic acids per gram mycelial dry weight.10 min-1. In the absence of added energy source, Vmax of 0.05 mg humic acids per gram mycelial dry wt.10 min-1 was obtained; however, the affinity for humic acids by this uptake system was the same as for the energy-driven process. Apparent binding of humic acids to cell structures was indicated because only 41.8% of the humic acids taken up by the energy-dependent system could be recovered."}
{"id": "PMID:26457", "title": "Induction of autolysis in Bacillus subtilis by ochratoxin A.", "content": "Ochratoxin A (OTA) added during the exponential growth phase at a concentration higher than 12 microgram/ml caused autolysis of Bacillus subtilis. Optical density of cultures decreased, and at higher concentrations the cultures became sterile. Optimum OTA-induced lysis was about pH 5. At concentrations below 10 microgram/ml, protein synthesis was inhibited more strongly than RNA synthesis. Cell wall synthesis was also strongly inhibited. A fraction extracted from the lysates had the property of a lysis inhibitor. The relevance of this fraction in respect to autolysis is discussed.", "contents": "Induction of autolysis in Bacillus subtilis by ochratoxin A. Ochratoxin A (OTA) added during the exponential growth phase at a concentration higher than 12 microgram/ml caused autolysis of Bacillus subtilis. Optical density of cultures decreased, and at higher concentrations the cultures became sterile. Optimum OTA-induced lysis was about pH 5. At concentrations below 10 microgram/ml, protein synthesis was inhibited more strongly than RNA synthesis. Cell wall synthesis was also strongly inhibited. A fraction extracted from the lysates had the property of a lysis inhibitor. The relevance of this fraction in respect to autolysis is discussed."}
{"id": "PMID:26458", "title": "Antifungal properties of 2-alkynoic acids and their methyl esters.", "content": "Thirteen 2-alkynoic acids and their methyl esters (C3--C12, C14, C16, and C18) were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabouraud dextrose agar at pH 4.0 and 5.6. Toxicity to Candida albicans, Trichophyton mentagrophytes, and Mucro mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The fungitoxicity of the acids was influenced by chain length, pH of the medium, and absence or presence of adsorbents. The toxicity of the esters was influenced primarily by chain length and to a lesser extent by the pH of the medium and the presence of beef serum. The order of activity of the 2-alkynoic acids is C10=C11=C12 greater than C14=C16 greater than C9 greater than C8 greater than C7. When compared with other fatty acid analogs, the order of fungitoxicity on a weight basis is 2-alkynoic acids greater than 2-alkenoic acids greater than alkanoic acids greater than 2-bromoalkanoic acids greater than 2-fluoroalkanoic acids. There is an inverse relationship between chain length and pKa of the acids, suggesting that partition behavior is a fundamental determinant of fungitoxicity along with the effect of adsorbents.", "contents": "Antifungal properties of 2-alkynoic acids and their methyl esters. Thirteen 2-alkynoic acids and their methyl esters (C3--C12, C14, C16, and C18) were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabouraud dextrose agar at pH 4.0 and 5.6. Toxicity to Candida albicans, Trichophyton mentagrophytes, and Mucro mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The fungitoxicity of the acids was influenced by chain length, pH of the medium, and absence or presence of adsorbents. The toxicity of the esters was influenced primarily by chain length and to a lesser extent by the pH of the medium and the presence of beef serum. The order of activity of the 2-alkynoic acids is C10=C11=C12 greater than C14=C16 greater than C9 greater than C8 greater than C7. When compared with other fatty acid analogs, the order of fungitoxicity on a weight basis is 2-alkynoic acids greater than 2-alkenoic acids greater than alkanoic acids greater than 2-bromoalkanoic acids greater than 2-fluoroalkanoic acids. There is an inverse relationship between chain length and pKa of the acids, suggesting that partition behavior is a fundamental determinant of fungitoxicity along with the effect of adsorbents."}
{"id": "PMID:26459", "title": "Prescribing of psychoactive drugs for chronically ill elderly patients.", "content": "The prescribing of psychoactive drugs for 1431 chronically ill elderly patients being assessed for long-term institutional or community care was surveyed. Psychoactive drugs had been prescribed for about one quarter of the patients; benzodiazepines were the most frequently prescribed group. Judging from the extensive prescribing of flurazepam and chloral hydrate, commonly used hypnotics, the main reason psychoactive drugs were prescribed was to provide night-time sedation. Antidepressants and drugs promoted as useful in improving cognitive function were infrequently prescribed. Commendable prescribing practices included the infrequent use of \"cerebral vasodilators\" and barbiturates. Questionable prescribing practices included the infrequent use of tricyclic antidepressants in severely depressed patients and the use of tranquilizers in patients described by their attending physician as markedly or extremely withdrawn.", "contents": "Prescribing of psychoactive drugs for chronically ill elderly patients. The prescribing of psychoactive drugs for 1431 chronically ill elderly patients being assessed for long-term institutional or community care was surveyed. Psychoactive drugs had been prescribed for about one quarter of the patients; benzodiazepines were the most frequently prescribed group. Judging from the extensive prescribing of flurazepam and chloral hydrate, commonly used hypnotics, the main reason psychoactive drugs were prescribed was to provide night-time sedation. Antidepressants and drugs promoted as useful in improving cognitive function were infrequently prescribed. Commendable prescribing practices included the infrequent use of \"cerebral vasodilators\" and barbiturates. Questionable prescribing practices included the infrequent use of tricyclic antidepressants in severely depressed patients and the use of tranquilizers in patients described by their attending physician as markedly or extremely withdrawn."}
{"id": "PMID:26460", "title": "Clinical pharmacology and therapeutics of benzodiazepines.", "content": "Benzodiazepines are among the most commonly prescribed drugs in the world. In contrast to their extensive use, the therapeutic indications and potential of benzodiazepines are limited. All benzodiazepine derivatives available in Canada are similar structurally and in their pharmacologic actions. Few have specific advantages over any others. For example, no benzodiazepine has been shown to be superior to chlordiazepoxide in the treatment of acute anxiety, chronic anxiety neurosis or insomnia. Barbiturates should not be prescribed for these problems since benzodiazepines are just as effective and are safer. Persons more than 70 years old should receive initial doses of benzodiazepines 50% less than those prescribed for younger persons, and individuals with cirrhosis should receive chlordiazepoxide or diazepam in one third the usual dose; oxazepam or lorazepam should be considered for these two groups of patients. Diazepam and chlordiazepoxide should not be given intramuscularly. Benzodiazepines should be prescribed only when clearly indicated and only for the necessary length of time.", "contents": "Clinical pharmacology and therapeutics of benzodiazepines. Benzodiazepines are among the most commonly prescribed drugs in the world. In contrast to their extensive use, the therapeutic indications and potential of benzodiazepines are limited. All benzodiazepine derivatives available in Canada are similar structurally and in their pharmacologic actions. Few have specific advantages over any others. For example, no benzodiazepine has been shown to be superior to chlordiazepoxide in the treatment of acute anxiety, chronic anxiety neurosis or insomnia. Barbiturates should not be prescribed for these problems since benzodiazepines are just as effective and are safer. Persons more than 70 years old should receive initial doses of benzodiazepines 50% less than those prescribed for younger persons, and individuals with cirrhosis should receive chlordiazepoxide or diazepam in one third the usual dose; oxazepam or lorazepam should be considered for these two groups of patients. Diazepam and chlordiazepoxide should not be given intramuscularly. Benzodiazepines should be prescribed only when clearly indicated and only for the necessary length of time."}
{"id": "PMID:26462", "title": "Heat fractionation and thermotolerance: a review.", "content": "A rational approach to the design of clinical protocols combining fractionated hyperthermia plus X-irradiation or hyperthermia plus chemotherapy requires an understanding of the biology of fractionated heat alone. Mammalian cells growing in vitro can dramatically increase their tolerance to thermal damage (i.e., reduce the cellular inactivation rate) after prior heat conditioning. Although the mechanism(s) for this cellular thermotolerance is still unknown, it is apparent that the thermal history, the heat fractionation interval, and the recovery conditions all modify significantly the degree of thermotolerance subsequently exhibited. At the tissue level, the role of cellular thermotolerance is further complicated by host physiological mechanisms. Few data are available on heat fractionation in vivo, and the relative importance of physiological versus cellular effects remains to be defined.", "contents": "Heat fractionation and thermotolerance: a review. A rational approach to the design of clinical protocols combining fractionated hyperthermia plus X-irradiation or hyperthermia plus chemotherapy requires an understanding of the biology of fractionated heat alone. Mammalian cells growing in vitro can dramatically increase their tolerance to thermal damage (i.e., reduce the cellular inactivation rate) after prior heat conditioning. Although the mechanism(s) for this cellular thermotolerance is still unknown, it is apparent that the thermal history, the heat fractionation interval, and the recovery conditions all modify significantly the degree of thermotolerance subsequently exhibited. At the tissue level, the role of cellular thermotolerance is further complicated by host physiological mechanisms. Few data are available on heat fractionation in vivo, and the relative importance of physiological versus cellular effects remains to be defined."}
{"id": "PMID:26464", "title": "Purification and properties of acid ribonucleases in human serum and leukocytes.", "content": "Acid RNase was purified from normal human serum about 2400-fold by chromatography on phosphocellulose and Sephadex G-75 and rechromatography on Sephadex G-75. Assayed with yeast RNA as substrate, the enzyme showed the maximal activity at about pH 6.5 with sodium phosphate buffer. The reaction was activated by Na+, K+, and spermine, but it was not affected greatly by Mg2+, Co2+, and EDTA. Ca2+, Fe2+, Zn2+, and Cu2+ inhibited the reaction. Among the synthetic substrates examined, the enzyme preferentially hydrolyzed pyrimidine nucleotides, with a higher affinity for polycytidylate than for polyuridylate. The enzyme was thermolabile, but it stabilized with bovine plasma albumin. The molecular weight was approximately 15,000, estimated gel filtration on Sephadex G-75, and its isoelectric pH was above 11.0. From normal human leukocytes, acid RNase was purified about 400-fold by the same procedure described previously except that rechromatography on Sephadex G-75 was omitted. The properties of leukocytic RNase were found to be similar to those of serum acid RNase, but the latter enzyme differed in substrate specificity substantially from leukocytic RNase, preferring polyuridylate to polycytidylate. This evidence shows that serum RNase is not of leukocytic origin under normal physiological conditions.", "contents": "Purification and properties of acid ribonucleases in human serum and leukocytes. Acid RNase was purified from normal human serum about 2400-fold by chromatography on phosphocellulose and Sephadex G-75 and rechromatography on Sephadex G-75. Assayed with yeast RNA as substrate, the enzyme showed the maximal activity at about pH 6.5 with sodium phosphate buffer. The reaction was activated by Na+, K+, and spermine, but it was not affected greatly by Mg2+, Co2+, and EDTA. Ca2+, Fe2+, Zn2+, and Cu2+ inhibited the reaction. Among the synthetic substrates examined, the enzyme preferentially hydrolyzed pyrimidine nucleotides, with a higher affinity for polycytidylate than for polyuridylate. The enzyme was thermolabile, but it stabilized with bovine plasma albumin. The molecular weight was approximately 15,000, estimated gel filtration on Sephadex G-75, and its isoelectric pH was above 11.0. From normal human leukocytes, acid RNase was purified about 400-fold by the same procedure described previously except that rechromatography on Sephadex G-75 was omitted. The properties of leukocytic RNase were found to be similar to those of serum acid RNase, but the latter enzyme differed in substrate specificity substantially from leukocytic RNase, preferring polyuridylate to polycytidylate. This evidence shows that serum RNase is not of leukocytic origin under normal physiological conditions."}
{"id": "PMID:26465", "title": "Serum acid ribonuclease in myelogenous leukemia.", "content": "Acid and alkaline RNase activities in serum were measured with yeast RNA as the substrate in normal subjects and in leukemic patients pretreatment and posttreatment, and the acid/alkaline ratios of activities were 0.63 +/- 0.08 (S.D.) (N, 12), 2.28 +/- 0.82 (N, 8), and 0.60 +/- 0.13 (N, 9), respectively. The mean value for the ratio in the pretreated leukemia was significantly higher than that in the other 2 groups (p less than 0.01). By separating these acid and alkaline RNases from normal and leukemic sera by phosphocellulose chromatography, it was further confirmed that acid RNase alone increased markedly in leukemic serum. From serum and leukocytes of leukemic patients, acid RNases were purified about 2000-fold and 300-fold, respectively, by phosphocellulose and Sephadex G-75 chromatography. Both enzymes displayed properties nearly identical with those of normal serum and leukocytes, except that leukemic serum acid RNase had about a 2.4-fold greater affinity for polyuridylate than for polycytidylate as substrate, in contrast to normal serum acid RNase that degraded polycytidylate exclusively. On the other hand acid RNases from serum leukocytes of leukemia showed a similar substrate preference. These results suggest that the high RNase levels of leukemic sera are due to an excessive leakage of acid RNase into the blood stream from abnormal leukocytes.", "contents": "Serum acid ribonuclease in myelogenous leukemia. Acid and alkaline RNase activities in serum were measured with yeast RNA as the substrate in normal subjects and in leukemic patients pretreatment and posttreatment, and the acid/alkaline ratios of activities were 0.63 +/- 0.08 (S.D.) (N, 12), 2.28 +/- 0.82 (N, 8), and 0.60 +/- 0.13 (N, 9), respectively. The mean value for the ratio in the pretreated leukemia was significantly higher than that in the other 2 groups (p less than 0.01). By separating these acid and alkaline RNases from normal and leukemic sera by phosphocellulose chromatography, it was further confirmed that acid RNase alone increased markedly in leukemic serum. From serum and leukocytes of leukemic patients, acid RNases were purified about 2000-fold and 300-fold, respectively, by phosphocellulose and Sephadex G-75 chromatography. Both enzymes displayed properties nearly identical with those of normal serum and leukocytes, except that leukemic serum acid RNase had about a 2.4-fold greater affinity for polyuridylate than for polycytidylate as substrate, in contrast to normal serum acid RNase that degraded polycytidylate exclusively. On the other hand acid RNases from serum leukocytes of leukemia showed a similar substrate preference. These results suggest that the high RNase levels of leukemic sera are due to an excessive leakage of acid RNase into the blood stream from abnormal leukocytes."}
{"id": "PMID:26467", "title": "Changes in small vessel blood content of the rat heart induced by hypercapnic, hyperoxic or asphyxic conditions.", "content": "The small vessel blood content (SVBC) of the ventricular walls of the heart of anesthetized closed chest rats was determined using 59FeC13 to label the plasma siderophilin. SVBC was measured breathing air, 100% O2, 5% CO2 in 21% O2 and during asphyxia. The average SVBC could be ranked: air less than 100% O2 less than 5% CO2 less than asphyxia. Only the '100% O2' values were not significantly above the 'air' values. Under control conditions, SVBC of the rat heart averaged 6.77 +/-(SE) 0.23 ml blood/100 g tissue. Inhalation of 5% CO2 increased this to 8.68 +/- 0.34, while asphyxia produced a maximal response to 14.40 +/- 0.77. Comparison of SVBC were made between various regions of the ventricular walls. The only significant difference was that the right side of the septum had a lower SVBC than the left ventricular subepicardium under all conditions except CO2. These differences in SVBC are related to the number of open capillaries in the myocardium. Thus inhalation of CO2 decreases intercapillary distance while 100% O2 has no effect.", "contents": "Changes in small vessel blood content of the rat heart induced by hypercapnic, hyperoxic or asphyxic conditions. The small vessel blood content (SVBC) of the ventricular walls of the heart of anesthetized closed chest rats was determined using 59FeC13 to label the plasma siderophilin. SVBC was measured breathing air, 100% O2, 5% CO2 in 21% O2 and during asphyxia. The average SVBC could be ranked: air less than 100% O2 less than 5% CO2 less than asphyxia. Only the '100% O2' values were not significantly above the 'air' values. Under control conditions, SVBC of the rat heart averaged 6.77 +/-(SE) 0.23 ml blood/100 g tissue. Inhalation of 5% CO2 increased this to 8.68 +/- 0.34, while asphyxia produced a maximal response to 14.40 +/- 0.77. Comparison of SVBC were made between various regions of the ventricular walls. The only significant difference was that the right side of the septum had a lower SVBC than the left ventricular subepicardium under all conditions except CO2. These differences in SVBC are related to the number of open capillaries in the myocardium. Thus inhalation of CO2 decreases intercapillary distance while 100% O2 has no effect."}
{"id": "PMID:26479", "title": "[Purification of rat brain guanylate cyclase].", "content": "The purification of guanylate cyclase has been achieved. After electrophoresis on polyacrylamide gel only one protein band was observed. The low factor of purification must therefore be ascribed to the loss of an activator of guanylate cyclase. Stimulation of the activity by nitroprusside is also lost during purification. The purified enzyme follows Michaelis--Menten kinetics, it is activated by Mn++ ions and inhibited by triphospho nucleotides.", "contents": "[Purification of rat brain guanylate cyclase]. The purification of guanylate cyclase has been achieved. After electrophoresis on polyacrylamide gel only one protein band was observed. The low factor of purification must therefore be ascribed to the loss of an activator of guanylate cyclase. Stimulation of the activity by nitroprusside is also lost during purification. The purified enzyme follows Michaelis--Menten kinetics, it is activated by Mn++ ions and inhibited by triphospho nucleotides."}
{"id": "PMID:26481", "title": "Isolation of gamma-glutamyltransferase from human liver, and comparison with the enzyme from human kidney.", "content": "We isolated gamma-glutamyltransferase [(gamma-glutamyl)-peptide:amino acid gamma-glutamyltransferase, EC 2.3.2.2] from human liver and compared some of its properties with the same enzyme prepared from human kidney. The enzymes from these two sources are very similar with respect to initial velocity kinetic constants, pH optima of the transpeptidation and autotransfer reactions, heat stability, competitive inhibition by glutathione of the colorimetric assay in which gamma-glutamyl-4-nitroanilide is substrate, stability of catalytic activity to trypsinization, and relative rates of transfer of the gamma-glutamyl moiety from gamma-glutamyl-4-nitroanilide and L-[glycine-2-3/]glutathione to some amino acids and small peptides. The kidney enzyme is inhibited more by the gamma-glutamyl acceptor substrate, glycylglycine, as reflected in a sevenfold lower value for the inhibition constant KiA. Major differences were observed in the lectin-binding properties of liver gamma-glutamyltransferase compared to the kidney enzyme. Lectin-binding property differences are retained for the trypsinized form of the liver and kidney enzymes, although the degree of precipitation was less for certain lectins as compared to the untreated enzyme. Lectin-binding properties were reversed by carbohydrates specific for each lectin. We adapted the histochemical staining technique of Rutenberg et al. [J. Histochem. Cytochem. 17, 517 (1969)] to the detection of gamma-glutamyltransferase activity in acrylamide gels; diffusion artifacts are minimized and the color produced is stable for several days. Untreated and trypsinized forms of the liver enzyme both migrated faster in acrylamide gels (as single bands) than did the corresponding forms of the kidney enzyme.", "contents": "Isolation of gamma-glutamyltransferase from human liver, and comparison with the enzyme from human kidney. We isolated gamma-glutamyltransferase [(gamma-glutamyl)-peptide:amino acid gamma-glutamyltransferase, EC 2.3.2.2] from human liver and compared some of its properties with the same enzyme prepared from human kidney. The enzymes from these two sources are very similar with respect to initial velocity kinetic constants, pH optima of the transpeptidation and autotransfer reactions, heat stability, competitive inhibition by glutathione of the colorimetric assay in which gamma-glutamyl-4-nitroanilide is substrate, stability of catalytic activity to trypsinization, and relative rates of transfer of the gamma-glutamyl moiety from gamma-glutamyl-4-nitroanilide and L-[glycine-2-3/]glutathione to some amino acids and small peptides. The kidney enzyme is inhibited more by the gamma-glutamyl acceptor substrate, glycylglycine, as reflected in a sevenfold lower value for the inhibition constant KiA. Major differences were observed in the lectin-binding properties of liver gamma-glutamyltransferase compared to the kidney enzyme. Lectin-binding property differences are retained for the trypsinized form of the liver and kidney enzymes, although the degree of precipitation was less for certain lectins as compared to the untreated enzyme. Lectin-binding properties were reversed by carbohydrates specific for each lectin. We adapted the histochemical staining technique of Rutenberg et al. [J. Histochem. Cytochem. 17, 517 (1969)] to the detection of gamma-glutamyltransferase activity in acrylamide gels; diffusion artifacts are minimized and the color produced is stable for several days. Untreated and trypsinized forms of the liver enzyme both migrated faster in acrylamide gels (as single bands) than did the corresponding forms of the kidney enzyme."}
{"id": "PMID:26483", "title": "Biochemical characterization of an aryl acetic ester hydrolase isolated from human monocytes.", "content": "A carboxylic-ester hydrolase was isolated from the leukocytes of a patient with myelomonocytic leukemia. Its relative molecular mass as estimated by sucrose density-gradient sedimentation is about 70 000. The purified enzyme is specific for acetyl esters of aromatic alcohols. It is inhibited by fluoride, but insensitive to eserine or p-chloromercuriphenylsulfonate. Hydrolysis of 1-naphthyl acetate was optimal above pH 6.0; of o-nitrophenyl acetate, above 8.0. The common catalytic site for the two types of substrates on the enzyme was confirmed by competitive inhibition data.", "contents": "Biochemical characterization of an aryl acetic ester hydrolase isolated from human monocytes. A carboxylic-ester hydrolase was isolated from the leukocytes of a patient with myelomonocytic leukemia. Its relative molecular mass as estimated by sucrose density-gradient sedimentation is about 70 000. The purified enzyme is specific for acetyl esters of aromatic alcohols. It is inhibited by fluoride, but insensitive to eserine or p-chloromercuriphenylsulfonate. Hydrolysis of 1-naphthyl acetate was optimal above pH 6.0; of o-nitrophenyl acetate, above 8.0. The common catalytic site for the two types of substrates on the enzyme was confirmed by competitive inhibition data."}
{"id": "PMID:26484", "title": "A novel gamma-glutamyl transpeptidase in renal carcinoma in comparison with normal kidney enzyme.", "content": "A novel gamma-glutamyl transpeptidase was found in a renal carcinoma tissue. This enzyme electrophoresed more quickly than that of normal kidney, but more slowly than normal liver enzyme. Their Rf values are 0.46, 0.33, and 0.52 for the renal carcinoma, normal kidney and normal liver enzyme, respectively. After treatment of the renal carcinoma and normal kidney enzyme with neuraminidase, the renal carcinoma gamma-glutamyl transpeptidase still electrophoresed slightly faster than that of normal kidney. The catalytic properties of the renal carcinoma gamma-glutamyl transpeptidase were almost the same as those of normal kidney except for molecular weight; the molecular weight for the renal carcinoma was estimated to be about 130 000, while that of normal kidney was about 90 000. These results may mean that the enzyme of the renal carcinoma is different from that of normal kidney in chemical constituents other than sialic acid. Of 10 patients with renal carcinoma examined electrophoretically, 5 posessed this novel enzyme in their renal carcinoma tissues.", "contents": "A novel gamma-glutamyl transpeptidase in renal carcinoma in comparison with normal kidney enzyme. A novel gamma-glutamyl transpeptidase was found in a renal carcinoma tissue. This enzyme electrophoresed more quickly than that of normal kidney, but more slowly than normal liver enzyme. Their Rf values are 0.46, 0.33, and 0.52 for the renal carcinoma, normal kidney and normal liver enzyme, respectively. After treatment of the renal carcinoma and normal kidney enzyme with neuraminidase, the renal carcinoma gamma-glutamyl transpeptidase still electrophoresed slightly faster than that of normal kidney. The catalytic properties of the renal carcinoma gamma-glutamyl transpeptidase were almost the same as those of normal kidney except for molecular weight; the molecular weight for the renal carcinoma was estimated to be about 130 000, while that of normal kidney was about 90 000. These results may mean that the enzyme of the renal carcinoma is different from that of normal kidney in chemical constituents other than sialic acid. Of 10 patients with renal carcinoma examined electrophoretically, 5 posessed this novel enzyme in their renal carcinoma tissues."}
{"id": "PMID:26485", "title": "A simple radioimmunoassay for plasma cortisol.", "content": "A simple radioimmunoassay (RIA) for plasma cortisol is described which combines the advantages of (i) direct analysis of untreated plasma samples, (ii) use of solid-coupled anti-cortisol antibodies and (iii) use of a gamma-labelled radioligand. The reagents are relatively easily prepared and stable, and the analysis can be completed in 4 h. Inter-assay precision (C.V.) is 8-11%. Critical examination of specificity using high pressure liquid chromatography showed that 23-35% of the immunoassayable material in plasma was not cortisol. RIA results on samples collected under basal conditions were on average 40 nmol/l lower than fluorimetric results, while in insulin hypoglycaemia and synacthen (ACTH) stimulation tests, this difference increased to over 100 nmol/l. The RIA is technically more simple than fluorimetric, competitive-protein-binding, and many RIA methods, and can be used with advantage in the routine investigation of adrenocortical function. However, using the present antiserum, the RIA is not applicable to investigations on patients receiving metyrapone, nor in suspected cases of congenital adrenal hyperplasia.", "contents": "A simple radioimmunoassay for plasma cortisol. A simple radioimmunoassay (RIA) for plasma cortisol is described which combines the advantages of (i) direct analysis of untreated plasma samples, (ii) use of solid-coupled anti-cortisol antibodies and (iii) use of a gamma-labelled radioligand. The reagents are relatively easily prepared and stable, and the analysis can be completed in 4 h. Inter-assay precision (C.V.) is 8-11%. Critical examination of specificity using high pressure liquid chromatography showed that 23-35% of the immunoassayable material in plasma was not cortisol. RIA results on samples collected under basal conditions were on average 40 nmol/l lower than fluorimetric results, while in insulin hypoglycaemia and synacthen (ACTH) stimulation tests, this difference increased to over 100 nmol/l. The RIA is technically more simple than fluorimetric, competitive-protein-binding, and many RIA methods, and can be used with advantage in the routine investigation of adrenocortical function. However, using the present antiserum, the RIA is not applicable to investigations on patients receiving metyrapone, nor in suspected cases of congenital adrenal hyperplasia."}
{"id": "PMID:26486", "title": "Purification and serological studies of human alpha-L-fucosidase in the normal and fucosidosis states.", "content": "An antiserum has been raised to purified alpha-L-fucosidase. Levels of cross-reaction with serum of two unrelated fucosidosis patients and normal individuals with low activity are consistent with the presence of very low amounts of normal enzyme. Similarly no cross-reacting material could be found in cultured fibroblasts from fucosidosis patients. It is deduced that in these cases there is no production of mutant enzyme in quantities comparable to normal levels. Some observations on the interrelations of fucosidases I and II are reported.", "contents": "Purification and serological studies of human alpha-L-fucosidase in the normal and fucosidosis states. An antiserum has been raised to purified alpha-L-fucosidase. Levels of cross-reaction with serum of two unrelated fucosidosis patients and normal individuals with low activity are consistent with the presence of very low amounts of normal enzyme. Similarly no cross-reacting material could be found in cultured fibroblasts from fucosidosis patients. It is deduced that in these cases there is no production of mutant enzyme in quantities comparable to normal levels. Some observations on the interrelations of fucosidases I and II are reported."}
{"id": "PMID:26487", "title": "Sphingomyelinase activity levels in human peripheral blood leukocytes, using [3H]sphingomyelin as substrate: study of heterozygotes and homozygotes for Niemann-Pick disease variants.", "content": "Patients and heterozygous carriers of Niemann-Pick disease types A and B as well as the primary (genetic) sea-blue histiocyte syndrome were investigated for their leukocyte sphingomyelinase activity. In parallel, glucocerebrosidase activity was determined in all cases studied. [3H]Sphingomyelin and [14C]glucocerebroside served as substrates for sphingomyelinase and glucocerebrosidase activity measurements, respectively. Conditions for these enzymes' assays are discussed. Sphingomyelinase activity was completely absent in three cases of Niemann-Pick disease type A and significantly diminished in one patient with Niemann-Pick disease type B and two with the sea-blue histiocyte syndrome. Sphingomyelinase activity in obligatory heterozygotes of all variants investigated represented about 40 to 70% of normal activity. Nevertheless, some overlapping with normal values occasionally occurred. Interestingly, glucocerbrosidase activity was elevated in patients with Niemann-Pick disease variants.", "contents": "Sphingomyelinase activity levels in human peripheral blood leukocytes, using [3H]sphingomyelin as substrate: study of heterozygotes and homozygotes for Niemann-Pick disease variants. Patients and heterozygous carriers of Niemann-Pick disease types A and B as well as the primary (genetic) sea-blue histiocyte syndrome were investigated for their leukocyte sphingomyelinase activity. In parallel, glucocerebrosidase activity was determined in all cases studied. [3H]Sphingomyelin and [14C]glucocerebroside served as substrates for sphingomyelinase and glucocerebrosidase activity measurements, respectively. Conditions for these enzymes' assays are discussed. Sphingomyelinase activity was completely absent in three cases of Niemann-Pick disease type A and significantly diminished in one patient with Niemann-Pick disease type B and two with the sea-blue histiocyte syndrome. Sphingomyelinase activity in obligatory heterozygotes of all variants investigated represented about 40 to 70% of normal activity. Nevertheless, some overlapping with normal values occasionally occurred. Interestingly, glucocerbrosidase activity was elevated in patients with Niemann-Pick disease variants."}
{"id": "PMID:26488", "title": "Serum alanine assay with an enzymic micromethod (L-alanine dehydrogenase).", "content": "L-Alanine was measured by an enzymic micromethod in serum after treatment with perchloric acid, as well as after ultrafiltration through collodium membrane filters. Serum L-alanine was also determined by an automated column chromatographic technique. Using the enzymic method, spuriously increased L-alanine levels could be obtained due to the absorbent reaction between hydrazine and NAD-containing reagents. It could be shown that this absorbent reaction depends on the pH value of the test solution. In contrast to supernatant diluted by perchloric acid, ultrafiltrates gave L-alanine data equivalent to those by column chromatography, since conditions of reaction time and pH value could be kept identical for blank, standard and ultrafiltrate solutions.", "contents": "Serum alanine assay with an enzymic micromethod (L-alanine dehydrogenase). L-Alanine was measured by an enzymic micromethod in serum after treatment with perchloric acid, as well as after ultrafiltration through collodium membrane filters. Serum L-alanine was also determined by an automated column chromatographic technique. Using the enzymic method, spuriously increased L-alanine levels could be obtained due to the absorbent reaction between hydrazine and NAD-containing reagents. It could be shown that this absorbent reaction depends on the pH value of the test solution. In contrast to supernatant diluted by perchloric acid, ultrafiltrates gave L-alanine data equivalent to those by column chromatography, since conditions of reaction time and pH value could be kept identical for blank, standard and ultrafiltrate solutions."}
{"id": "PMID:26489", "title": "Interaction of [14C]acetylsalicylic acid with normal human peripheral blood lymphocytes.", "content": "Therapeutic concentrations of acetylsalicylic acid (ASA) have strikingly inhibited in vitro and in vivo mitogen- and antigen-induced blastogenesis by human lymphocytes. These observations may be pertinent to the anti-inflammatory actions of ASA. To investigate further the possible effects of ASA on cellular responses, we studied the in vitro interaction of [14C]ASA with lymphocytes. Results indicated that the [14C]ASA association with cells was (a) proportional to ASA concentrations, (b) non-saturable at high concentrations of ASA, (c) dependent on pH, (d) independent of temperature, (e) dependent on cell concentration, (f) not consistently displaced by unlabelled ASA or other drugs, (g) rapid and unchanged over 1 min to 72 hr incubations and (h) reversed by repeated cell washing. These data confirmed that ASA indeed interacted with lymphocytes. The association was rapid, reversible, pH-dependent and not demonstrably specific under these experimental conditions.", "contents": "Interaction of [14C]acetylsalicylic acid with normal human peripheral blood lymphocytes. Therapeutic concentrations of acetylsalicylic acid (ASA) have strikingly inhibited in vitro and in vivo mitogen- and antigen-induced blastogenesis by human lymphocytes. These observations may be pertinent to the anti-inflammatory actions of ASA. To investigate further the possible effects of ASA on cellular responses, we studied the in vitro interaction of [14C]ASA with lymphocytes. Results indicated that the [14C]ASA association with cells was (a) proportional to ASA concentrations, (b) non-saturable at high concentrations of ASA, (c) dependent on pH, (d) independent of temperature, (e) dependent on cell concentration, (f) not consistently displaced by unlabelled ASA or other drugs, (g) rapid and unchanged over 1 min to 72 hr incubations and (h) reversed by repeated cell washing. These data confirmed that ASA indeed interacted with lymphocytes. The association was rapid, reversible, pH-dependent and not demonstrably specific under these experimental conditions."}
{"id": "PMID:26493", "title": "Clorazepate kinetics in treated epileptics.", "content": "Clorazepate is decarboxylated to form desmethyldiazepam and is a convenient way of administering it. Its kinetics were investigated in epileptic patients after single oral and multiple oral doses. Peak serum concentrations of demethyldiazepam occurred in 0.5 to 1 hr. There appeared to be a brief lag before rapid absorption. Because of the rapid absorption with resulting high serum levels, daily doses should be divided. Serum concentration/time curves were best fitted by the two-compartment open model. The apparent t1/2 of the distribution phase was 1.28 +/- 0.44 hr and the t1/2 of the disposition phase was 40.8 +/- 9.96 hr. Serum concentrations rose after meals. Whole body apparent volume of distribution (VB/F) was 1.63 +/- 0.24 L/kg. Total plasma clearance was 34.4 +/- 7.2 ml/min, which is greater than clearance levels for desmethyldiazepam in normals and reflects the greater hepatic metabolism which occurs in treated epileptics. The discrepancy illustrates the hazards of extrapolating data collected in normals to patients with multiple drug exposures.", "contents": "Clorazepate kinetics in treated epileptics. Clorazepate is decarboxylated to form desmethyldiazepam and is a convenient way of administering it. Its kinetics were investigated in epileptic patients after single oral and multiple oral doses. Peak serum concentrations of demethyldiazepam occurred in 0.5 to 1 hr. There appeared to be a brief lag before rapid absorption. Because of the rapid absorption with resulting high serum levels, daily doses should be divided. Serum concentration/time curves were best fitted by the two-compartment open model. The apparent t1/2 of the distribution phase was 1.28 +/- 0.44 hr and the t1/2 of the disposition phase was 40.8 +/- 9.96 hr. Serum concentrations rose after meals. Whole body apparent volume of distribution (VB/F) was 1.63 +/- 0.24 L/kg. Total plasma clearance was 34.4 +/- 7.2 ml/min, which is greater than clearance levels for desmethyldiazepam in normals and reflects the greater hepatic metabolism which occurs in treated epileptics. The discrepancy illustrates the hazards of extrapolating data collected in normals to patients with multiple drug exposures."}
{"id": "PMID:26494", "title": "Barbiturate physical dependence in mice: effects of neuroleptics and diazepam on the withdrawal syndrome.", "content": "Diazepam (8 mg/kg) quickly and effectively reduced the incidence of withdrawal symptoms in phenobarbital dependent C57BL/6J male mice. In contrast, the neuroleptic agents employed (chlorpormazine, haloperidol, or reserpine) or alpha-methyl-p-tyrosine tended to exacerbate the withdrawal syndrome. Chlorpromazine and haloperidol were approximately equally potent in their effects; this would suggest that their antidopaminergic effects were not the primary mechanism of action for the increased incidence of withdrawal symptoms.", "contents": "Barbiturate physical dependence in mice: effects of neuroleptics and diazepam on the withdrawal syndrome. Diazepam (8 mg/kg) quickly and effectively reduced the incidence of withdrawal symptoms in phenobarbital dependent C57BL/6J male mice. In contrast, the neuroleptic agents employed (chlorpormazine, haloperidol, or reserpine) or alpha-methyl-p-tyrosine tended to exacerbate the withdrawal syndrome. Chlorpromazine and haloperidol were approximately equally potent in their effects; this would suggest that their antidopaminergic effects were not the primary mechanism of action for the increased incidence of withdrawal symptoms."}
{"id": "PMID:26490", "title": "The cardiovascular effects of intraventricular 5,6-dihydroxytryptamine in conscious hypertensive rats.", "content": "1. Conscious experimental hypertensive rats injected intraventricularly with 5,6-dihydroxytryptamine (50 microgram) responded with a rapid and long-lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration. 2. The acute actions of 5,6-dihydroxytryptamine on the cardiovascular system were not modified by pretreatment with bromolysergide (0.5 mg/kg, i.p.), methysergide (2.5 mg/kg, i.p.) or intraventricular phentolamine (200 microgram). 3. The results suggest that central serotonergic neurones play an important role in the regulation of blood pressure. However, the site of action remains to be investigated.", "contents": "The cardiovascular effects of intraventricular 5,6-dihydroxytryptamine in conscious hypertensive rats. 1. Conscious experimental hypertensive rats injected intraventricularly with 5,6-dihydroxytryptamine (50 microgram) responded with a rapid and long-lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration. 2. The acute actions of 5,6-dihydroxytryptamine on the cardiovascular system were not modified by pretreatment with bromolysergide (0.5 mg/kg, i.p.), methysergide (2.5 mg/kg, i.p.) or intraventricular phentolamine (200 microgram). 3. The results suggest that central serotonergic neurones play an important role in the regulation of blood pressure. However, the site of action remains to be investigated."}
{"id": "PMID:26516", "title": "Comparative trial of two antihistamines, mequitazine and brompheniramine.", "content": "A double-blind trial was carried out in 48 patients with allergic disorders to compare the efficacy and tolerance of mequitazine and brompheniramine. Patients received either 10 mg mequitazine or 24 mg brompheniramine daily, divided into 2 doses, for 14 days. The results, analyzed from patients' answers to a questionnaire recorded on a daily basis, showed that mequitazine was at least as effective as brompheniramine and caused significantly less drowsiness throughout the trial period. Few other side-effects were reported.", "contents": "Comparative trial of two antihistamines, mequitazine and brompheniramine. A double-blind trial was carried out in 48 patients with allergic disorders to compare the efficacy and tolerance of mequitazine and brompheniramine. Patients received either 10 mg mequitazine or 24 mg brompheniramine daily, divided into 2 doses, for 14 days. The results, analyzed from patients' answers to a questionnaire recorded on a daily basis, showed that mequitazine was at least as effective as brompheniramine and caused significantly less drowsiness throughout the trial period. Few other side-effects were reported."}
{"id": "PMID:26517", "title": "Comparative trial of an antihistamine, mequitazine, and placebo.", "content": "Forty patients suffering from a dermatological condition suitable for treatment with an antihistamine were studied in a double-blind randomized trial to compare the effectiveness and tolerance of mequitazine and placebo. Over a period of 2 weeks, patients received either 5 mg mequitazine twice daily or placebo. Where justified, patients were also given concomitant topical treatment but only with a hydrating cream or ichthyol paste. Patients' overall response to treatment was significantly better in the mequitazine group, whether the results were analyzed for all patients or those receiving just the trial drugs without topical treatment. Few side-effects were reported and there was no significant difference between the levels of drowsiness experienced with mequitazine compared with placebo.", "contents": "Comparative trial of an antihistamine, mequitazine, and placebo. Forty patients suffering from a dermatological condition suitable for treatment with an antihistamine were studied in a double-blind randomized trial to compare the effectiveness and tolerance of mequitazine and placebo. Over a period of 2 weeks, patients received either 5 mg mequitazine twice daily or placebo. Where justified, patients were also given concomitant topical treatment but only with a hydrating cream or ichthyol paste. Patients' overall response to treatment was significantly better in the mequitazine group, whether the results were analyzed for all patients or those receiving just the trial drugs without topical treatment. Few side-effects were reported and there was no significant difference between the levels of drowsiness experienced with mequitazine compared with placebo."}
{"id": "PMID:26518", "title": "Double-blind clinical comparison between a gastrin-receptor antagonist, proglumide, and a histamine H2-blocker, cimetidine.", "content": "A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine. Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.", "contents": "Double-blind clinical comparison between a gastrin-receptor antagonist, proglumide, and a histamine H2-blocker, cimetidine. A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine. Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide."}
{"id": "PMID:26519", "title": "Dose-ranging study of the new beta-adrenergic antagonist nadolol in the treatment of essential hypertension.", "content": "A preliminary, single-blind, dose-ranging study was carried out in 30 patients with essential hypertension to assess the efficacy of nadolol, a new beta-adrenoceptor blocking agent without intrinsic sympathomimetic action and with an extremely long plasma half-life. After a 2-week period on placebo, patients were treated for 14 weeks with daily doses of 40 mg nadolol (20 mg twice daily). Dosage was increased every second week up to a maximum of 560 mg daily or until the patient was stabilized at an effective normotensive dose level. The results showed that at the end of the trial period there was a significant reduction in both systolic and diastolic blood pressure (approximately 34/21 mmHg) at an average daily dose of 110 mg nadolol. Apart from a tendency to bradycardia, explained by the drug's lack of sympathomimetic action, no other side-effects attributable to treatment were reported and no patient complained of sleep disturbance.", "contents": "Dose-ranging study of the new beta-adrenergic antagonist nadolol in the treatment of essential hypertension. A preliminary, single-blind, dose-ranging study was carried out in 30 patients with essential hypertension to assess the efficacy of nadolol, a new beta-adrenoceptor blocking agent without intrinsic sympathomimetic action and with an extremely long plasma half-life. After a 2-week period on placebo, patients were treated for 14 weeks with daily doses of 40 mg nadolol (20 mg twice daily). Dosage was increased every second week up to a maximum of 560 mg daily or until the patient was stabilized at an effective normotensive dose level. The results showed that at the end of the trial period there was a significant reduction in both systolic and diastolic blood pressure (approximately 34/21 mmHg) at an average daily dose of 110 mg nadolol. Apart from a tendency to bradycardia, explained by the drug's lack of sympathomimetic action, no other side-effects attributable to treatment were reported and no patient complained of sleep disturbance."}
{"id": "PMID:26520", "title": "Comparison of the new beta-adrenoceptor antagonist, nadolol, and propranolol in the treatment of angina pectoris.", "content": "A randomized, double-blind study was carried out in 24 patients with stable angina pectoris to compare the efficacy of nadolol, a new beta-adrenoceptor antagonist, and propranolol. After a period on placebo, 14 patients received nadolol once daily and 10 patients propranolol 4-times daily over a 10-week dose-ranging period followed by a maintenance period of 4 weeks. Optimal daily dosage for nadolol was 100 mg, and 112 mg for propranolol. Parameters used for evaluation of therapeutic effects included the number of anginal attacks, number of nitroglycerine tablets needed, time before onset of chest pain during exercise test, exercise time, and overall clinical impression of response. The results indicated that nadolol given once daily was equally as effective as propranolol 4-times daily in treating angina pectoris.", "contents": "Comparison of the new beta-adrenoceptor antagonist, nadolol, and propranolol in the treatment of angina pectoris. A randomized, double-blind study was carried out in 24 patients with stable angina pectoris to compare the efficacy of nadolol, a new beta-adrenoceptor antagonist, and propranolol. After a period on placebo, 14 patients received nadolol once daily and 10 patients propranolol 4-times daily over a 10-week dose-ranging period followed by a maintenance period of 4 weeks. Optimal daily dosage for nadolol was 100 mg, and 112 mg for propranolol. Parameters used for evaluation of therapeutic effects included the number of anginal attacks, number of nitroglycerine tablets needed, time before onset of chest pain during exercise test, exercise time, and overall clinical impression of response. The results indicated that nadolol given once daily was equally as effective as propranolol 4-times daily in treating angina pectoris."}
{"id": "PMID:26522", "title": "Cutaneous vasculitis.", "content": "Cutaneous vasculitis is a common but confusing clinical syndrome. We report three illustrative cases demonstrating the variable nature of the process. Renal disease is generally a poor prognostic sign; therefore, the renal status should be evaluated early. The process probably represents an immune complex disorder. Although various therapies have been used, an aggressive corticosteroid regimen is the preferred mode of treatment at the current time.", "contents": "Cutaneous vasculitis. Cutaneous vasculitis is a common but confusing clinical syndrome. We report three illustrative cases demonstrating the variable nature of the process. Renal disease is generally a poor prognostic sign; therefore, the renal status should be evaluated early. The process probably represents an immune complex disorder. Although various therapies have been used, an aggressive corticosteroid regimen is the preferred mode of treatment at the current time."}
{"id": "PMID:26523", "title": "Metabolism of 5-isopropyl-1-methyl-2-nitro-1H-imidazole. Identification of some urinary metabolites in the dog.", "content": "The metabolism of 5-isopropyl-1-methyl-2-nitro-1H-[2-14C] imidazole in dogs has been investigated after oral administration of 50 mg/kg. Three main metabolites, still containing the nitro group and accounting for about 50% of the total radiocarbon, together with a small amount of the unchanged drug, were isolated from the urine within 48 hr. The structures were determined by mass, infrared, and nuclear magnetic resonance spectroscopy. The biotransformations giving rise to the metabolites isolated involve the isopropyl chain of the molecule, either at the tertiary carbon atom or at one of the two methyl groups, or both. Thus, the metabolic behavior of this 2-nitroimidazole derivative appears to be similar to that previously demonstrated for the class of the isomeric 5-nitroimidazoles.", "contents": "Metabolism of 5-isopropyl-1-methyl-2-nitro-1H-imidazole. Identification of some urinary metabolites in the dog. The metabolism of 5-isopropyl-1-methyl-2-nitro-1H-[2-14C] imidazole in dogs has been investigated after oral administration of 50 mg/kg. Three main metabolites, still containing the nitro group and accounting for about 50% of the total radiocarbon, together with a small amount of the unchanged drug, were isolated from the urine within 48 hr. The structures were determined by mass, infrared, and nuclear magnetic resonance spectroscopy. The biotransformations giving rise to the metabolites isolated involve the isopropyl chain of the molecule, either at the tertiary carbon atom or at one of the two methyl groups, or both. Thus, the metabolic behavior of this 2-nitroimidazole derivative appears to be similar to that previously demonstrated for the class of the isomeric 5-nitroimidazoles."}
{"id": "PMID:26524", "title": "Formation of sulfone metabolites from chlorpromazine and perazine in man.", "content": "Didesmethylchlorpromazine sulfone [gamma-(2-chlorophenothiazinyl-10)-propylamine sulfone] has been isolated from the urine of a patient under continuous chlorpromazine therapy and identified by mass spectrometry. The same compound was present in organs of rats after injection of the corresponding sulfide. The Cl-free analogue, gamma-(phenothiazinyl-10)-propylamine sulfone, was excreted by patients receiving perazine and by a volunteer after ingestion of the primary amine sulfoxide.", "contents": "Formation of sulfone metabolites from chlorpromazine and perazine in man. Didesmethylchlorpromazine sulfone [gamma-(2-chlorophenothiazinyl-10)-propylamine sulfone] has been isolated from the urine of a patient under continuous chlorpromazine therapy and identified by mass spectrometry. The same compound was present in organs of rats after injection of the corresponding sulfide. The Cl-free analogue, gamma-(phenothiazinyl-10)-propylamine sulfone, was excreted by patients receiving perazine and by a volunteer after ingestion of the primary amine sulfoxide."}
{"id": "PMID:26525", "title": "Comparison of biliary excretory function and bile composition in male, female, and lactating female rats.", "content": "The rates of excretion of phenol-3,6-dibromphthalein disulfonate, ouabain, indocyanine green, and amaranth into the bile of male and female rats were found to be similar. The rates of bile production in male and female rats were also similar whereas that of lactating rats was 50% greater. The increase in bile production occurred during pregnancy and decreased rapidly after removal of the pups from the dam. The increased bile production was of canalicular origin and was due to an increase in both the bile salt-dependent and independent fractions. The lactating rats tended to excrete some xenobiotics more rapidly than did the other rats, but no difference in the biliary excretion was observed in male and female rats.", "contents": "Comparison of biliary excretory function and bile composition in male, female, and lactating female rats. The rates of excretion of phenol-3,6-dibromphthalein disulfonate, ouabain, indocyanine green, and amaranth into the bile of male and female rats were found to be similar. The rates of bile production in male and female rats were also similar whereas that of lactating rats was 50% greater. The increase in bile production occurred during pregnancy and decreased rapidly after removal of the pups from the dam. The increased bile production was of canalicular origin and was due to an increase in both the bile salt-dependent and independent fractions. The lactating rats tended to excrete some xenobiotics more rapidly than did the other rats, but no difference in the biliary excretion was observed in male and female rats."}
{"id": "PMID:26527", "title": "Dihydropyrimidinase. Stereochemistry of the metabolism of some 5-alkylhydantoins.", "content": "The (R)- and (S)-isomers of 5-methylhydantoin (5-MH) and of 5-isopropylhydantoin (5-IPH) were synthesized, and incubations of the individual isomers with a rat liver dihydropyrimidinase preparation (100,000g supernatant fraction) were carried out. Only the (R)-isomer of 5-MH or 5-IPH was ring-opened by the enzyme. Reversibility of the enzymatic ring-opening reaction could be demonstrated with only the (R)-isomer of 2-methylhydantoic acid (2-MHA) or 2-isopropylhydantoic acid (2-IPHA). The results of the present investigation show that the replacement in 5-phenylhydantoin of the phenyl group with an alkyl group does not alter the stereospecificity of the hydantoin substrates in the ring-opening reaction. The results are used to form the concept that (R)-dihydrothymine, the optical isomer previously postulated as the natural substrate to the enzyme, may have a different type of binding at the active site of the enzyme.", "contents": "Dihydropyrimidinase. Stereochemistry of the metabolism of some 5-alkylhydantoins. The (R)- and (S)-isomers of 5-methylhydantoin (5-MH) and of 5-isopropylhydantoin (5-IPH) were synthesized, and incubations of the individual isomers with a rat liver dihydropyrimidinase preparation (100,000g supernatant fraction) were carried out. Only the (R)-isomer of 5-MH or 5-IPH was ring-opened by the enzyme. Reversibility of the enzymatic ring-opening reaction could be demonstrated with only the (R)-isomer of 2-methylhydantoic acid (2-MHA) or 2-isopropylhydantoic acid (2-IPHA). The results of the present investigation show that the replacement in 5-phenylhydantoin of the phenyl group with an alkyl group does not alter the stereospecificity of the hydantoin substrates in the ring-opening reaction. The results are used to form the concept that (R)-dihydrothymine, the optical isomer previously postulated as the natural substrate to the enzyme, may have a different type of binding at the active site of the enzyme."}
{"id": "PMID:26528", "title": "Dihydropyrimidinase. Metabolism of some cyclic imides of different ring size.", "content": "The ability of dihydropyrimidinase (EC 3.5.2.2) to hydrolyze cyclic imides of different ring size was investigated. Succinimide, glutarimide, and adipimide are five-, six-, and seven-membered cyclic imides, respectively. The ring-opened compounds that correspond to these cyclic imides are, respectively, succinamic, glutaramic, and adipamic acid. In incubations of cyclic imides (pH 8, 1 hr) with a rat liver dihydropyrimidinase preparation from which omega-amidase had been removed, adipimide was classed as a good substrate and succinimide and glutarimide were classed as very poor but definite substrates. alpha-Phenylsuccinimide, the N-demethylated metabolite of phensuximide, was a much better substrate than succinimide. alpha-Phenylglutarimide was not a substrate. The in vitro studies of the present investigation were in agreement with observations made in previous in vivo studies.", "contents": "Dihydropyrimidinase. Metabolism of some cyclic imides of different ring size. The ability of dihydropyrimidinase (EC 3.5.2.2) to hydrolyze cyclic imides of different ring size was investigated. Succinimide, glutarimide, and adipimide are five-, six-, and seven-membered cyclic imides, respectively. The ring-opened compounds that correspond to these cyclic imides are, respectively, succinamic, glutaramic, and adipamic acid. In incubations of cyclic imides (pH 8, 1 hr) with a rat liver dihydropyrimidinase preparation from which omega-amidase had been removed, adipimide was classed as a good substrate and succinimide and glutarimide were classed as very poor but definite substrates. alpha-Phenylsuccinimide, the N-demethylated metabolite of phensuximide, was a much better substrate than succinimide. alpha-Phenylglutarimide was not a substrate. The in vitro studies of the present investigation were in agreement with observations made in previous in vivo studies."}
{"id": "PMID:26529", "title": "Metabolism and tissue distribution of mono-2-ethylhexyl phthalate in the rat.", "content": "The absorption, distribution and metabolic excretion of mono-2-ethylhexyl [7-14C]phthalate (MEHP) were studied in the rat. This compound was readily absorbed from the gastrointestinal tract. Radioactivity following intravenous administration of 14C-MEHP was rapidly distributed in all tissues, with the highest levels occurring in the liver, kidney, and urinary bladder. Excretion of radioactivity was rapid and approximately 80% of the dose was eliminated 24 hr after oral administration, 72% in the urine and 8% in feces. MEHP was extensively metabolized after oral administration, and the major urinary metabolites were identified as an alcohol, a ketone, and an acid resulting from the side-chain oxidation of MEHP. A trace of o-phthalic acid was also identified.", "contents": "Metabolism and tissue distribution of mono-2-ethylhexyl phthalate in the rat. The absorption, distribution and metabolic excretion of mono-2-ethylhexyl [7-14C]phthalate (MEHP) were studied in the rat. This compound was readily absorbed from the gastrointestinal tract. Radioactivity following intravenous administration of 14C-MEHP was rapidly distributed in all tissues, with the highest levels occurring in the liver, kidney, and urinary bladder. Excretion of radioactivity was rapid and approximately 80% of the dose was eliminated 24 hr after oral administration, 72% in the urine and 8% in feces. MEHP was extensively metabolized after oral administration, and the major urinary metabolites were identified as an alcohol, a ketone, and an acid resulting from the side-chain oxidation of MEHP. A trace of o-phthalic acid was also identified."}
{"id": "PMID:26530", "title": "Species, sex, and developmental differences in the O- and N-dealkylation of ethylmorphine by hepatic microsomes.", "content": "3-O-[1'-14C]Ethylmorphine and ethylmorphine, respectively, were used to measure O- and N-dealkylase activities of hepatic microsomes. The well-known sex difference in the rate of N-delakylation in mature rats was not observed with O-dealkylation, nor did O-dealkylase activity increase as male rats reached maturity, as is the case with N-dealkylase activity. Accordingly, O-dealkylation represents only about 20% of the total dealkylase activity (O- + N-) in mature male rats, but about 50% in mature female rats. A comparison of the O- and N-dealkylating activities of hepatic microsomes from rats, mice, guinea pigs, and rabbits showed that both the rates of O- and N-dealkylation and the ratio of the two reactions vary greatly among animal species. These studies contribute to the evidence that different cytochrome P-450-dependent mono-oxygenase systems are involved in the O- and N-dealkylation of opium alkaloids.", "contents": "Species, sex, and developmental differences in the O- and N-dealkylation of ethylmorphine by hepatic microsomes. 3-O-[1'-14C]Ethylmorphine and ethylmorphine, respectively, were used to measure O- and N-dealkylase activities of hepatic microsomes. The well-known sex difference in the rate of N-delakylation in mature rats was not observed with O-dealkylation, nor did O-dealkylase activity increase as male rats reached maturity, as is the case with N-dealkylase activity. Accordingly, O-dealkylation represents only about 20% of the total dealkylase activity (O- + N-) in mature male rats, but about 50% in mature female rats. A comparison of the O- and N-dealkylating activities of hepatic microsomes from rats, mice, guinea pigs, and rabbits showed that both the rates of O- and N-dealkylation and the ratio of the two reactions vary greatly among animal species. These studies contribute to the evidence that different cytochrome P-450-dependent mono-oxygenase systems are involved in the O- and N-dealkylation of opium alkaloids."}
{"id": "PMID:26532", "title": "Levodopa pharmacokinetics. Alterations after benserazide, a decarboxylase inhibitor.", "content": "Plasma levodopa decay curves appeared to be triexponential up to 6 hr after single intravenous injections of levodopa in rats, rabbits, and dogs. After pretreatment of each of these three species with benserazide (Ro-4-4602), a decarboxylase inhibitor, plasma levodopa concentrations declined biexponentially. Administration of benserazide decreased both total plasma clearance and apparent volume of distribution of levodopa, but did not change the rate constant of the terminal phase of the plasma levodopa decay curve. Thus, decarboxylase inhibition failed to alter the plasma half-life of levodopa.", "contents": "Levodopa pharmacokinetics. Alterations after benserazide, a decarboxylase inhibitor. Plasma levodopa decay curves appeared to be triexponential up to 6 hr after single intravenous injections of levodopa in rats, rabbits, and dogs. After pretreatment of each of these three species with benserazide (Ro-4-4602), a decarboxylase inhibitor, plasma levodopa concentrations declined biexponentially. Administration of benserazide decreased both total plasma clearance and apparent volume of distribution of levodopa, but did not change the rate constant of the terminal phase of the plasma levodopa decay curve. Thus, decarboxylase inhibition failed to alter the plasma half-life of levodopa."}
{"id": "PMID:26533", "title": "Biotransformation products of 3,4,4'-trichlorocarbanilide in rat, monkey, and man.", "content": "3,4,4'-Trichlorocarbanilide (TCC), uniformly labeled with 14C in the monochloro ring, was administered to rats, rhesus monkeys, and humans. Radioactive materials in the plasma and urine of all three species and in the bile of rats and monkeys were separated by high performance liquid chromatography. The chromatography showed great similarity between the monkey and the human. Principal metabolites common to all species were the sulfate and glucuronide conjugates of 2'-, 3'-, and 6-hydroxy-TCC. The rat also produced the glucuronide and sulfate conjugates of 2',6-dihydroxy-TCC. The major urinary excretion products found in humans and monkeys were the N- and N'-TCC glucuronides.", "contents": "Biotransformation products of 3,4,4'-trichlorocarbanilide in rat, monkey, and man. 3,4,4'-Trichlorocarbanilide (TCC), uniformly labeled with 14C in the monochloro ring, was administered to rats, rhesus monkeys, and humans. Radioactive materials in the plasma and urine of all three species and in the bile of rats and monkeys were separated by high performance liquid chromatography. The chromatography showed great similarity between the monkey and the human. Principal metabolites common to all species were the sulfate and glucuronide conjugates of 2'-, 3'-, and 6-hydroxy-TCC. The rat also produced the glucuronide and sulfate conjugates of 2',6-dihydroxy-TCC. The major urinary excretion products found in humans and monkeys were the N- and N'-TCC glucuronides."}
{"id": "PMID:26534", "title": "The absorption, excretion, and biotransformation of 3,4,4'-trichlorocarbanilide in humans.", "content": "The metabolism and disposition of 14C-TCC (3,4,4'-trichlorocarbanilide) have been evaluated in humans following oral exposure to 2.2 mumol/kg body wt. Fecal elimination (70% of dose) was complete 120 hr after dosing and the urinary excretion (27% of dose) was completed in 80 hr. The maximum plasma level occurred 2.8 hr after dosing and was 3.7 nmol-equivalents of TCC per g of plasma (approximately 1.2 ppm). Biotransformation of TCC was rapid but did not appear to involve splitting of the basic TCC structure. The major plasma metabolites were N- and N'-glucuronides of TCC which were eliminated with t1/2 approximately 2 hr to the urine and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (the o-hydroxy-TCC sulfates) which were removed with t1/2 approximately 20 hr (presumably into the bile). It is concluded that a nonradioactive analytical method based on the urinary excretion of the N-glucuronides would be suitable for the determination of TCC absorption in humans.", "contents": "The absorption, excretion, and biotransformation of 3,4,4'-trichlorocarbanilide in humans. The metabolism and disposition of 14C-TCC (3,4,4'-trichlorocarbanilide) have been evaluated in humans following oral exposure to 2.2 mumol/kg body wt. Fecal elimination (70% of dose) was complete 120 hr after dosing and the urinary excretion (27% of dose) was completed in 80 hr. The maximum plasma level occurred 2.8 hr after dosing and was 3.7 nmol-equivalents of TCC per g of plasma (approximately 1.2 ppm). Biotransformation of TCC was rapid but did not appear to involve splitting of the basic TCC structure. The major plasma metabolites were N- and N'-glucuronides of TCC which were eliminated with t1/2 approximately 2 hr to the urine and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (the o-hydroxy-TCC sulfates) which were removed with t1/2 approximately 20 hr (presumably into the bile). It is concluded that a nonradioactive analytical method based on the urinary excretion of the N-glucuronides would be suitable for the determination of TCC absorption in humans."}
{"id": "PMID:26535", "title": "Metabolism of cyclobenzaprine in the dog.", "content": "Ten metabolites of cyclobenzaprine, accounting for approximately 50% of the urinary radioactivity, were identified in the urine of dogs to which the labeled drug had been given orally. These included the 1,2-dihydrodiol, three phenolic derivatives, the N-oxide, the 10,11-epoxide, the 10,11-glycol, desmethylcyclobenzaprine, and the glucuronide conjugates of desmethylcyclobenzaprine and cyclobenzaprine. The metabolites were excreted in both the free and conjugated states. Unchanged cyclobenzaprine was present in only minor amounts.", "contents": "Metabolism of cyclobenzaprine in the dog. Ten metabolites of cyclobenzaprine, accounting for approximately 50% of the urinary radioactivity, were identified in the urine of dogs to which the labeled drug had been given orally. These included the 1,2-dihydrodiol, three phenolic derivatives, the N-oxide, the 10,11-epoxide, the 10,11-glycol, desmethylcyclobenzaprine, and the glucuronide conjugates of desmethylcyclobenzaprine and cyclobenzaprine. The metabolites were excreted in both the free and conjugated states. Unchanged cyclobenzaprine was present in only minor amounts."}
{"id": "PMID:26536", "title": "Pharmacokinetic model of presystemic metabolism.", "content": "A pharmacokinetic perfusion model is presented that describes the disposition of drugs that are subject to both first-pass hepatic and intestinal epithelial metabolism. Equations are developed to estimate hepatic and intestinal epithelial clearances by determining drug concentrations as a function of time in both portal and peripheral vein blood after oral and iv administration, and by determining or estimating the flow rate of blood perfusing the gastrointestinal tissues. A method that can be used, under the stated conditions, to approximate the systemic availability after oral administration of drugs subject to presystemic metabolism is also developed.", "contents": "Pharmacokinetic model of presystemic metabolism. A pharmacokinetic perfusion model is presented that describes the disposition of drugs that are subject to both first-pass hepatic and intestinal epithelial metabolism. Equations are developed to estimate hepatic and intestinal epithelial clearances by determining drug concentrations as a function of time in both portal and peripheral vein blood after oral and iv administration, and by determining or estimating the flow rate of blood perfusing the gastrointestinal tissues. A method that can be used, under the stated conditions, to approximate the systemic availability after oral administration of drugs subject to presystemic metabolism is also developed."}
{"id": "PMID:26538", "title": "Studies on metabolism of bromazepam. VI. Reduction of 2-(2-amino-5-bromobenzoyl)pyridine, a metabolite of bromazepam, in the rabbit, rat, and guinea pig.", "content": "Three urinary metabolites that were formed by cleavage of the benzodiazepine ring of bromazepam, 2-(2-amino-5-bromobenzoyl)pyridine (ABBP), 2-(2-amino-5-bromo-3-hydroxybenzoyl)pyridine (3-OH-ABBP), and 2-amino-5-bromo-2'-azabenzhydrol (ABAB), were measured in urine of rabbits, rats, and guinea pigs. The major metabolite was 3-OH-ABBP in all animals given bromazepam orally. ABAB was also excreted in major amounts in the guinea pig, but was excreted in minor amounts in the rabbit and rat. Moreover, ABAB was excreted in the urine of all animals given ABBP orally. It may be concluded that ABAB was formed by reduction of the carbonyl group of ABBP. ABBP reduction was catalyzed by NADPH-dependent enzymes occurring in rabbit liver cytoplasm, and rat liver microsomes, and guinea pig liver cytoplasm and microsomes. The reductases were inhibited by sulfhydryl group reagents. The optimum pH of the cytoplasmic enzyme ranged from 7.2 to 7.8, and that of the microsomal enzyme was 6.5. The apparent KM value for the reduction of ABBP by guinea pig liver microsomes was the lowest among all of the liver preparations.", "contents": "Studies on metabolism of bromazepam. VI. Reduction of 2-(2-amino-5-bromobenzoyl)pyridine, a metabolite of bromazepam, in the rabbit, rat, and guinea pig. Three urinary metabolites that were formed by cleavage of the benzodiazepine ring of bromazepam, 2-(2-amino-5-bromobenzoyl)pyridine (ABBP), 2-(2-amino-5-bromo-3-hydroxybenzoyl)pyridine (3-OH-ABBP), and 2-amino-5-bromo-2'-azabenzhydrol (ABAB), were measured in urine of rabbits, rats, and guinea pigs. The major metabolite was 3-OH-ABBP in all animals given bromazepam orally. ABAB was also excreted in major amounts in the guinea pig, but was excreted in minor amounts in the rabbit and rat. Moreover, ABAB was excreted in the urine of all animals given ABBP orally. It may be concluded that ABAB was formed by reduction of the carbonyl group of ABBP. ABBP reduction was catalyzed by NADPH-dependent enzymes occurring in rabbit liver cytoplasm, and rat liver microsomes, and guinea pig liver cytoplasm and microsomes. The reductases were inhibited by sulfhydryl group reagents. The optimum pH of the cytoplasmic enzyme ranged from 7.2 to 7.8, and that of the microsomal enzyme was 6.5. The apparent KM value for the reduction of ABBP by guinea pig liver microsomes was the lowest among all of the liver preparations."}
{"id": "PMID:26539", "title": "Metabolism of levorotary 4,5-dihydrodiazepam in the rat.", "content": "The metabolism of (-)-4,5-dihydrodiazepam (7-chloro-1,3,4,5-tetrahydro-1-methyl-5-phenyl-2H-1,4-benzo[2-14C]diazepin-2-one) (I) was investigated in rats. Metabolites from urine and bile extracts purified by thin-layer chromatography were identified by mass spectrometry. Diazepam and its main metabolites were found among the biotransformation products of I. Based on these findings, the most important identified metabolic route of the compound studied appears to be the formation of an unsaturated bond between the N4 and C5 atoms, and further transformation of the diazepam formed.", "contents": "Metabolism of levorotary 4,5-dihydrodiazepam in the rat. The metabolism of (-)-4,5-dihydrodiazepam (7-chloro-1,3,4,5-tetrahydro-1-methyl-5-phenyl-2H-1,4-benzo[2-14C]diazepin-2-one) (I) was investigated in rats. Metabolites from urine and bile extracts purified by thin-layer chromatography were identified by mass spectrometry. Diazepam and its main metabolites were found among the biotransformation products of I. Based on these findings, the most important identified metabolic route of the compound studied appears to be the formation of an unsaturated bond between the N4 and C5 atoms, and further transformation of the diazepam formed."}
{"id": "PMID:26541", "title": "Microsomal N-hydroxylation of trans-4'-alkoxy-4-acetamidostilbenes.", "content": "Hamster liver microsomes catalyze the N-hydroxylation of the 4'-OCH3, 4'-OCH2CH3, 4'-O(CH2)2CH3, and 4'-O(CH2)3CH3 analogs of trans-4-acetamidostilbene. Other metabolites which were identified were the O-deethylation product of the 4'-OCH2CH3 analog as well as the alpha,beta-epoxides of the 4'-OCH2CH3 and 4'-O(CH2)2CH3 compounds and the (omega-1)-hydroxylation product of trans-4'-n-butoxy-4-acetamidostilbene. The kinetics of metabolism of the 4'-O(CH2)3CH3 analog were determined, but the rates of formation of the metabolites of the other members of the series were not linearly related to substrate concentration.", "contents": "Microsomal N-hydroxylation of trans-4'-alkoxy-4-acetamidostilbenes. Hamster liver microsomes catalyze the N-hydroxylation of the 4'-OCH3, 4'-OCH2CH3, 4'-O(CH2)2CH3, and 4'-O(CH2)3CH3 analogs of trans-4-acetamidostilbene. Other metabolites which were identified were the O-deethylation product of the 4'-OCH2CH3 analog as well as the alpha,beta-epoxides of the 4'-OCH2CH3 and 4'-O(CH2)2CH3 compounds and the (omega-1)-hydroxylation product of trans-4'-n-butoxy-4-acetamidostilbene. The kinetics of metabolism of the 4'-O(CH2)3CH3 analog were determined, but the rates of formation of the metabolites of the other members of the series were not linearly related to substrate concentration."}
{"id": "PMID:26542", "title": "Microsomal mixed-function amine oxidase. Oxidation products of piperazine-substituted phenothiazine drugs.", "content": "Oxidation products of fluphenazide, thioproperazine, and trifluoperazine obtained in reactions catalyzed by homogeneous preparations of the microsomal mixed-function amine oxidase have been isolated and identified. Approximately 0.5 g of metabolite of each piperazine-substituted phenothiazine drug was prepared in reactors containing, as catalyst, the purified oxidase covalently attached to glass beads. Nuclear magnetic resonance spectra of the isolated products indicated that with all three substrates the enzyme preferentially catalyzes N-oxidation of the piperazine nitrogen furthest from the phenothiazine nitrogen atom. The enzyme-catalyzed oxidation is quite specific and oxidation of the sulfur or nitrogen atoms in the phenothiazine ring could not be detected. Concentrations of piperazine-substituted phenothiazines required to half-saturate the amine oxidase were in the micromolar range and at pH 8.3 and 37 degrees C, all those tested were oxidized at approximately 2 mumol/min/mg of enzyme. Kinetic constants for the piperazine-substituted phenothiazines were very similar to those obtained with phenothiazines containing a dimethylaminopropyl sidechain.", "contents": "Microsomal mixed-function amine oxidase. Oxidation products of piperazine-substituted phenothiazine drugs. Oxidation products of fluphenazide, thioproperazine, and trifluoperazine obtained in reactions catalyzed by homogeneous preparations of the microsomal mixed-function amine oxidase have been isolated and identified. Approximately 0.5 g of metabolite of each piperazine-substituted phenothiazine drug was prepared in reactors containing, as catalyst, the purified oxidase covalently attached to glass beads. Nuclear magnetic resonance spectra of the isolated products indicated that with all three substrates the enzyme preferentially catalyzes N-oxidation of the piperazine nitrogen furthest from the phenothiazine nitrogen atom. The enzyme-catalyzed oxidation is quite specific and oxidation of the sulfur or nitrogen atoms in the phenothiazine ring could not be detected. Concentrations of piperazine-substituted phenothiazines required to half-saturate the amine oxidase were in the micromolar range and at pH 8.3 and 37 degrees C, all those tested were oxidized at approximately 2 mumol/min/mg of enzyme. Kinetic constants for the piperazine-substituted phenothiazines were very similar to those obtained with phenothiazines containing a dimethylaminopropyl sidechain."}
{"id": "PMID:26544", "title": "Influence of pregnancy and folic acid on phenytoin metabolism by rat liver microsomes.", "content": "Liver microsomal suspensions from pregnant and nonpregnant Sprague-Dawley rats were assayed for NADPH-dependent metabolism of phenytoin to the hydroxylated products, 5-(rho-hydroxyphenyl)-5-phenylhydantoin (rhoHPPH) and 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)5-phenylhydantoin (H2DIOL). UDP-glucuronic acid-dependent glucuronyltransferase activity for conjugating rhoHPPH was also measured. The specific activity for formation of rhoHPPH decreased by 35% in 21-day pregnant rats compared with nonpregnant rats, whereas specific activity for production of H2DIOL was increased approximately 2-fold on the 7th and 14th but not the 21st day of pregnancy. Because of a 25% increase in liver weight during pregnancy, the total hepatic phenytoin hydroxylase activity in pregnant rats (day 21) was not significantly different from that of nonpregnant controls. Folic acid treatment during pregnancy prevented the decrease in phenytoin hydroxylase specific activity. The KM for production of either rhoHPPH or H2DIOL was similar (90 micrometer) in pregnant (day 21) and nonpregnant animals. Thus, overall hepatic microsomal enzyme activity for metabolizing phenytoin was not significantly reduced during pregnancy in rats, although the ratio of H2DIOL to rhoHPPH was increased during the first two weeks. Folic acid may play a role in pregnancy-associated changes in phenytoin hydroxylase activity.", "contents": "Influence of pregnancy and folic acid on phenytoin metabolism by rat liver microsomes. Liver microsomal suspensions from pregnant and nonpregnant Sprague-Dawley rats were assayed for NADPH-dependent metabolism of phenytoin to the hydroxylated products, 5-(rho-hydroxyphenyl)-5-phenylhydantoin (rhoHPPH) and 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)5-phenylhydantoin (H2DIOL). UDP-glucuronic acid-dependent glucuronyltransferase activity for conjugating rhoHPPH was also measured. The specific activity for formation of rhoHPPH decreased by 35% in 21-day pregnant rats compared with nonpregnant rats, whereas specific activity for production of H2DIOL was increased approximately 2-fold on the 7th and 14th but not the 21st day of pregnancy. Because of a 25% increase in liver weight during pregnancy, the total hepatic phenytoin hydroxylase activity in pregnant rats (day 21) was not significantly different from that of nonpregnant controls. Folic acid treatment during pregnancy prevented the decrease in phenytoin hydroxylase specific activity. The KM for production of either rhoHPPH or H2DIOL was similar (90 micrometer) in pregnant (day 21) and nonpregnant animals. Thus, overall hepatic microsomal enzyme activity for metabolizing phenytoin was not significantly reduced during pregnancy in rats, although the ratio of H2DIOL to rhoHPPH was increased during the first two weeks. Folic acid may play a role in pregnancy-associated changes in phenytoin hydroxylase activity."}
{"id": "PMID:26550", "title": "Quantitation of N-demethylantipyrine in biological samples and isolation and characterization of its glucuronic acid conjugate.", "content": "An improved method for quantitating N-demethylantipyrine (N-DEM-AP) in urine by gas chromatography or gas chromatography-mass spectrometry has been developed. Recovery of greater than 90% of N-DEM-AP was achieved by extraction of the sample at pH 1 after addition of 3-amino-1-phenyl-2-pyrazolin-5-one. The coefficient of variation of replicate analyses was 8%. N-DEM-AP was excreted in the urine as a glucuronic acid conjugate. This conjugate was isolated from the urine of an individual receiving antipyrine and purified. The NMR and mass-spectral data are consistent with the conjugate being an O-glucuronide of N-DEM-AP in its enol form.", "contents": "Quantitation of N-demethylantipyrine in biological samples and isolation and characterization of its glucuronic acid conjugate. An improved method for quantitating N-demethylantipyrine (N-DEM-AP) in urine by gas chromatography or gas chromatography-mass spectrometry has been developed. Recovery of greater than 90% of N-DEM-AP was achieved by extraction of the sample at pH 1 after addition of 3-amino-1-phenyl-2-pyrazolin-5-one. The coefficient of variation of replicate analyses was 8%. N-DEM-AP was excreted in the urine as a glucuronic acid conjugate. This conjugate was isolated from the urine of an individual receiving antipyrine and purified. The NMR and mass-spectral data are consistent with the conjugate being an O-glucuronide of N-DEM-AP in its enol form."}
{"id": "PMID:26549", "title": "Alterations in the pharmacokinetics of 3H-delta9-tetrahydrocannabinol in mice by bacterial endotoxin.", "content": "Mice were pretreated with either bacterial endotoxin (3 mg/kg, ip) or saline 3 hr prior to an ip injection of 100 mg of 3H-delta9-tetrahydrocannabinol (3H-delta9-THC) per kg, a combination that results in synergistic lethality. Five hours after the injection of 3H-delta9-THC, the endotoxin-pretreated mice contained a significantly greater amount of radioactivity in kidney, liver, heart, plasma, urine, and brain than those without pretreatment. However, the plasma and brain levels of the animals tested with both endotoxin and 3H-delta9-THC (100 mg/kg) were significantly less than those in mice treated only with 200 mg of 3H-delta9-THC per kg, a sublethal dose. The percentage of radioactivity corresponding to unchanged 3H-delta9-THC in extracts of livers and brains was significantly greater in the endotoxin-pretreatment group than in controls. The brain level of 3H-delta9-THC in the endotoxin-pretreated mice was 50% higher than that in the saline-pretreated mice 5 hr after 3H-delta9-THC (100 mg/kg) administration. However, the brain levels of 3H-delta9-THC in the mice treated with endotoxin and 3H-delta9-THC (100 mg/kg) was one-third of that in brains of mice receiving the LD50 of 3H-delta9-THC (300 mg/kg).", "contents": "Alterations in the pharmacokinetics of 3H-delta9-tetrahydrocannabinol in mice by bacterial endotoxin. Mice were pretreated with either bacterial endotoxin (3 mg/kg, ip) or saline 3 hr prior to an ip injection of 100 mg of 3H-delta9-tetrahydrocannabinol (3H-delta9-THC) per kg, a combination that results in synergistic lethality. Five hours after the injection of 3H-delta9-THC, the endotoxin-pretreated mice contained a significantly greater amount of radioactivity in kidney, liver, heart, plasma, urine, and brain than those without pretreatment. However, the plasma and brain levels of the animals tested with both endotoxin and 3H-delta9-THC (100 mg/kg) were significantly less than those in mice treated only with 200 mg of 3H-delta9-THC per kg, a sublethal dose. The percentage of radioactivity corresponding to unchanged 3H-delta9-THC in extracts of livers and brains was significantly greater in the endotoxin-pretreatment group than in controls. The brain level of 3H-delta9-THC in the endotoxin-pretreated mice was 50% higher than that in the saline-pretreated mice 5 hr after 3H-delta9-THC (100 mg/kg) administration. However, the brain levels of 3H-delta9-THC in the mice treated with endotoxin and 3H-delta9-THC (100 mg/kg) was one-third of that in brains of mice receiving the LD50 of 3H-delta9-THC (300 mg/kg)."}
{"id": "PMID:26552", "title": "The metabolism of (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid in chimpanzee and man.", "content": "The metabolism of the polyvalent saluretic agent (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid was studied in chimpanzee and man. The drug was well absorbed and extensively metabolized by man. Peak levels of drug (5--8 microgram/ml) occurred within 1.5--4.5 hr of drug administration. The plasma half-life was estimated to be 2 hr; a similar half-life was observed in the chimpanzee. Little unchanged drug (less than 10%) was excreted in the urine of either species. Similar metabolic profiles were obtained for man and chimpanzee. The major urinary metabolites resulted from hydroxylation of the cyclopentyl moiety, giving rise to a number of diastereomers. The alcohol metabolites were subsequently oxidized to the ketone. The excretion of the metabolites coincided with maximal excretion of sodium and chloride ions. The hydroxylated metabolites have intrinsic pharmacological activity.", "contents": "The metabolism of (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid in chimpanzee and man. The metabolism of the polyvalent saluretic agent (2-cyclopentyl-6,7-dichloro-2-methyl-1-oxo-5-indanyloxy)acetic acid was studied in chimpanzee and man. The drug was well absorbed and extensively metabolized by man. Peak levels of drug (5--8 microgram/ml) occurred within 1.5--4.5 hr of drug administration. The plasma half-life was estimated to be 2 hr; a similar half-life was observed in the chimpanzee. Little unchanged drug (less than 10%) was excreted in the urine of either species. Similar metabolic profiles were obtained for man and chimpanzee. The major urinary metabolites resulted from hydroxylation of the cyclopentyl moiety, giving rise to a number of diastereomers. The alcohol metabolites were subsequently oxidized to the ketone. The excretion of the metabolites coincided with maximal excretion of sodium and chloride ions. The hydroxylated metabolites have intrinsic pharmacological activity."}
{"id": "PMID:26551", "title": "Urinary metabolites of 3,5-di-(1-[13C]methyl-1-methylethyl)4-hydroxytoluene (BHT-13C) in man.", "content": "Butylated hydroxytoluene (BHT) containing the stable isotope 13C was synthesized from 2-[13C]methylpropan-2-ol. A minor constituent of urine following ingestion of BHT-13C by a human volunteer was identified as 3,5-di-(1-[13C]methyl-1-methylethyl)-4-hydroxybenzoic acid, The major metabolite detected was 13C-labeled 5-carboxy-7-(1-carboxy-1-methylethyl)-3,3-dimethyl-2-hydroxy-2,3-dihydrobenzofuran. Detailed spectral analysis provided the basis for structural assignment. No evidence was found for intermediate metabolites leading from BHT-13C to the above compounds. Analysis of one fraction indicated the presence of traces of S-(3,5-di-(1-[13C]methyl-1-methylethyl-4-hydroxy-benzyl)-N-acetylcysteine. Analysis of serum samples by gas chromatography detected only trace quantities of unchanged BHT. No evidence was found for the presence of other nonpolar or unconjugated metabolites.", "contents": "Urinary metabolites of 3,5-di-(1-[13C]methyl-1-methylethyl)4-hydroxytoluene (BHT-13C) in man. Butylated hydroxytoluene (BHT) containing the stable isotope 13C was synthesized from 2-[13C]methylpropan-2-ol. A minor constituent of urine following ingestion of BHT-13C by a human volunteer was identified as 3,5-di-(1-[13C]methyl-1-methylethyl)-4-hydroxybenzoic acid, The major metabolite detected was 13C-labeled 5-carboxy-7-(1-carboxy-1-methylethyl)-3,3-dimethyl-2-hydroxy-2,3-dihydrobenzofuran. Detailed spectral analysis provided the basis for structural assignment. No evidence was found for intermediate metabolites leading from BHT-13C to the above compounds. Analysis of one fraction indicated the presence of traces of S-(3,5-di-(1-[13C]methyl-1-methylethyl-4-hydroxy-benzyl)-N-acetylcysteine. Analysis of serum samples by gas chromatography detected only trace quantities of unchanged BHT. No evidence was found for the presence of other nonpolar or unconjugated metabolites."}
{"id": "PMID:26554", "title": "Elimination of radioactivity following administration of [15,16-3H]naltrexone to rats and guinea pigs.", "content": "The elimination of radioactivity after [15,16-3H]naltrexone administration was studied in rats and guinea pigs. An average of 42% of the dose was eliminated in urine and 55% in feces following administration of 1 mg/kg iv to each of three rats. Analysis of radioactivity in the excreta of one rat that received the same dose im yielded similar results. On the other hand, four guinea pigs that received 1 mg/kg iv excreted only 14% of the dose in feces and 84% in urine. Similar results were obtained following im administration to guinea pigs at 1 and 20 mg/kg doses. In guinea pig excreta, an average of 64% of the dose corresponded to naltrexone and conjugates, 19% to beta-naltrexol and conjugates, and 2% to alpha-naltrexol and conjugates. In urine, the radioactivity corresponding to alpha-naltrexol and naltrexone was present mainly in conjugated form, whereas apparent beta-naltrexol was mainly unconjugated. The radioactivity in feces corresponded principally to unconjugated naltrexone and beta-naltrexol.", "contents": "Elimination of radioactivity following administration of [15,16-3H]naltrexone to rats and guinea pigs. The elimination of radioactivity after [15,16-3H]naltrexone administration was studied in rats and guinea pigs. An average of 42% of the dose was eliminated in urine and 55% in feces following administration of 1 mg/kg iv to each of three rats. Analysis of radioactivity in the excreta of one rat that received the same dose im yielded similar results. On the other hand, four guinea pigs that received 1 mg/kg iv excreted only 14% of the dose in feces and 84% in urine. Similar results were obtained following im administration to guinea pigs at 1 and 20 mg/kg doses. In guinea pig excreta, an average of 64% of the dose corresponded to naltrexone and conjugates, 19% to beta-naltrexol and conjugates, and 2% to alpha-naltrexol and conjugates. In urine, the radioactivity corresponding to alpha-naltrexol and naltrexone was present mainly in conjugated form, whereas apparent beta-naltrexol was mainly unconjugated. The radioactivity in feces corresponded principally to unconjugated naltrexone and beta-naltrexol."}
{"id": "PMID:26555", "title": "Lipid-soluble inhibitors of dihydrofolate reductase. I. Kinetics, tissue distribution, and extent of metabolism of pyrimethamine, metoprine, and etoprine in the rat, dog, and man.", "content": "With the aim of developing anticancer compounds which overcome some of the clinical limitations of the polar dihydrofolate reductase inhibitor, methotrexate, the physicochemical properties, kinetics, and metabolism of a series of lipid-soluble 2,4-diamino-5-phenylpyrimidine folate antagonists have been studied. Metoprine and etoprine, potent inhibitors of mammalian dihydrofolate reductase, were compared with pyrimethamine, a widely used antimalarial drug. The development of assay procedures in our laboratory and the synthesis of radiolabeled compounds have enabled a comparison of the kinetic characteristics and tissue distribution of these compounds in several species. The relative lipophilicities as indicated by the octanol/water partition coefficient are: etoprine (log P = 3.19) greater than metoprine (log P = 2.82) greater than pyrimethamine (log P = 2.69). Etoprine has the greatest affinity for plasma proteins, but all three compounds are bound to human plasma protein by 87% or more at therapeutic concentrations. Pharmacokinetic studies in the mouse, rat, dog, and man indicate that metoprine has the longest plasma half-life in all four species. The mean plasma half-lives in man are: pyrimethamine, 85 hr; metoprine, 216 hr; etoprine, 176 hr.", "contents": "Lipid-soluble inhibitors of dihydrofolate reductase. I. Kinetics, tissue distribution, and extent of metabolism of pyrimethamine, metoprine, and etoprine in the rat, dog, and man. With the aim of developing anticancer compounds which overcome some of the clinical limitations of the polar dihydrofolate reductase inhibitor, methotrexate, the physicochemical properties, kinetics, and metabolism of a series of lipid-soluble 2,4-diamino-5-phenylpyrimidine folate antagonists have been studied. Metoprine and etoprine, potent inhibitors of mammalian dihydrofolate reductase, were compared with pyrimethamine, a widely used antimalarial drug. The development of assay procedures in our laboratory and the synthesis of radiolabeled compounds have enabled a comparison of the kinetic characteristics and tissue distribution of these compounds in several species. The relative lipophilicities as indicated by the octanol/water partition coefficient are: etoprine (log P = 3.19) greater than metoprine (log P = 2.82) greater than pyrimethamine (log P = 2.69). Etoprine has the greatest affinity for plasma proteins, but all three compounds are bound to human plasma protein by 87% or more at therapeutic concentrations. Pharmacokinetic studies in the mouse, rat, dog, and man indicate that metoprine has the longest plasma half-life in all four species. The mean plasma half-lives in man are: pyrimethamine, 85 hr; metoprine, 216 hr; etoprine, 176 hr."}
{"id": "PMID:26559", "title": "[Assessment of vigilance].", "content": "Two aspects of vigilance are to be distinguished: the quantitative one refers to sleep-wakefulness dimension and the qualitative one refers to focusing of attention. Their combination leads to a curvilinear relationship between activation and performances. After describing the psychometric characteristics of vigilance tests, some examples are given of simple paper-pencil or more sophisticated methods. Physiological indices are also approached. The sources of variation influencing vigilance measurement are presented and also some useful experimental designs. At last some remarks are made on statistical exploitation and interpretation of results.", "contents": "[Assessment of vigilance]. Two aspects of vigilance are to be distinguished: the quantitative one refers to sleep-wakefulness dimension and the qualitative one refers to focusing of attention. Their combination leads to a curvilinear relationship between activation and performances. After describing the psychometric characteristics of vigilance tests, some examples are given of simple paper-pencil or more sophisticated methods. Physiological indices are also approached. The sources of variation influencing vigilance measurement are presented and also some useful experimental designs. At last some remarks are made on statistical exploitation and interpretation of results."}
{"id": "PMID:26556", "title": "Pharmacokinetics and steady-state myocardial uptake of disopyramide in the dog.", "content": "The pharmacokinetics and steady-state myocardial uptake of the antiarrhythmic drug disopyramide (DP) were determined in dogs after oral or intravenous administration of [14C]disopyramide phosphate. DP was absorbed rapidly and its absolute oral bioavailability was about 70%. Significant dose-dependent kinetics were not apparent after 7.5- to 30-mg/kg po doses. Plasma half-lives of DP were about 2.9 and 1.2 hr after the po and iv doses, respectively. DP and its N-dealkylated metabolites were largely excreted in the urine and their composition was qualitatively similar after the po and iv doses. Marked differences in the protein binding of DP in human and dog plasma were found. In the papillary muscle, ventricular septum, and ventricles of one dog, the steady-state concentrations of DP and its less active mono-N-dealkylated metabolite were about twice those in plasma, whereas in the atria and tricuspid and mitral valves they were similar to those in plasma.", "contents": "Pharmacokinetics and steady-state myocardial uptake of disopyramide in the dog. The pharmacokinetics and steady-state myocardial uptake of the antiarrhythmic drug disopyramide (DP) were determined in dogs after oral or intravenous administration of [14C]disopyramide phosphate. DP was absorbed rapidly and its absolute oral bioavailability was about 70%. Significant dose-dependent kinetics were not apparent after 7.5- to 30-mg/kg po doses. Plasma half-lives of DP were about 2.9 and 1.2 hr after the po and iv doses, respectively. DP and its N-dealkylated metabolites were largely excreted in the urine and their composition was qualitatively similar after the po and iv doses. Marked differences in the protein binding of DP in human and dog plasma were found. In the papillary muscle, ventricular septum, and ventricles of one dog, the steady-state concentrations of DP and its less active mono-N-dealkylated metabolite were about twice those in plasma, whereas in the atria and tricuspid and mitral valves they were similar to those in plasma."}
{"id": "PMID:26560", "title": "[Influence of pipotiazine on schizophrenia].", "content": "This study is an account of thirty cases of schizophrenia treated experimentally in open with Pipotiazine (19366 R.P.), these cases, of the Kraepelin's Dementia Praecox type, in serious or complicated forms necessitating important measures of hospital care. The quantitative and qualitative therapeutic results, very favourable and original, consist in the transformation of these serious forms into simple or latent forms of schizophrenia. The undesirable effects, rare and always regressive, were all the smaller in the measure as the favourable effects were greater, which indicates a precise impact on certain determinants (central control of affectivity and the representation of the autonomous body). Pipotiazine develops a curative process in the personality characterized mainly by the emergence of lucidity, narcissistic euphoria (anti-persecutory and anti-splintering) and by the apprehension of intrapsychic splitting, setting in motion the necessary psychological task of reconstruction.", "contents": "[Influence of pipotiazine on schizophrenia]. This study is an account of thirty cases of schizophrenia treated experimentally in open with Pipotiazine (19366 R.P.), these cases, of the Kraepelin's Dementia Praecox type, in serious or complicated forms necessitating important measures of hospital care. The quantitative and qualitative therapeutic results, very favourable and original, consist in the transformation of these serious forms into simple or latent forms of schizophrenia. The undesirable effects, rare and always regressive, were all the smaller in the measure as the favourable effects were greater, which indicates a precise impact on certain determinants (central control of affectivity and the representation of the autonomous body). Pipotiazine develops a curative process in the personality characterized mainly by the emergence of lucidity, narcissistic euphoria (anti-persecutory and anti-splintering) and by the apprehension of intrapsychic splitting, setting in motion the necessary psychological task of reconstruction."}
{"id": "PMID:26561", "title": "Chorismate mutase/prephenate dehydratase from Escherichia coli K12. Effect of phenylalanine, NaCl and pH on the protein conformation.", "content": "The effects of phenylalanine, NaCl and pH on the conformation of chorismate mutase/prephenate dehydratase have been investigated, using measurements of far and near-ultraviolet circular dichroic spectra and ultraviolet difference spectra. At pH 8.2 in 20 mM Tris-Cl buffer the enzyme was found to contain 10-20% helix and 40-50% beta-structure. There was little or no change in these values on the addition of 1 mM phenylalanine (the allosteric effector) or 0.4 M NaCl or by decreasing the pH to 7.4. Both phenylalanine and NaCl caused significant changes in the conformation of the enzyme. The most prominent of these was the movement of a tryptophan residue into a more hydrophobic environment. There was also a slight perturbation of this tryptophan when the pH was decreased to 7.4. The conformational changes can explain sigmoidal kinetic behaviour observed previously [Gething et al. (1976) Eur. J. Biochem. 71, 317-325].", "contents": "Chorismate mutase/prephenate dehydratase from Escherichia coli K12. Effect of phenylalanine, NaCl and pH on the protein conformation. The effects of phenylalanine, NaCl and pH on the conformation of chorismate mutase/prephenate dehydratase have been investigated, using measurements of far and near-ultraviolet circular dichroic spectra and ultraviolet difference spectra. At pH 8.2 in 20 mM Tris-Cl buffer the enzyme was found to contain 10-20% helix and 40-50% beta-structure. There was little or no change in these values on the addition of 1 mM phenylalanine (the allosteric effector) or 0.4 M NaCl or by decreasing the pH to 7.4. Both phenylalanine and NaCl caused significant changes in the conformation of the enzyme. The most prominent of these was the movement of a tryptophan residue into a more hydrophobic environment. There was also a slight perturbation of this tryptophan when the pH was decreased to 7.4. The conformational changes can explain sigmoidal kinetic behaviour observed previously [Gething et al. (1976) Eur. J. Biochem. 71, 317-325]."}
{"id": "PMID:26562", "title": "Chorismate mutase/prephenate dehydratase from Escherichia coli K12. Binding studies with the allosteric effector phenylalanine.", "content": "The binding of phenylalanine to the allosteric site of chorismate mutase/prephenate dehydratase has been studied by steady-state dialysis. Under most of the experimental conditions examined positive co-operativity was observed for the binding of ligand up to 50% saturation and negative co-operativity above 50% saturation. In the presence of 0.4 M NaCl at pH 8.2 the co-operativity was positive at all phenylalanine concentrations and the maximal stoichiometry of 1 mol of phenylalanine/mol of enzyme subunit was observed. It was concluded that there is a single phenylalanine-binding site per subunit which is associated with the regulation of each of the mutase and dehydratase activities. The effects of enzyme concentration, NaCl, temperature and pH on the binding of phenylalanine have been investigated. Neither tyrosine nor tryptophan bound to the allosteric site of the enzyme. Enzyme that was desensitized to inhibition by phenylalanine following modification of three sulphydryl groups with 5,5'-dithio-bis (2-nitrobenzoic acid) did not bind phenylalanine. The mechanism of co-operativity, the binding of the enzyme to Sepharosyl-phenylalanine and the physiological significance of the inhibition of the enzyme by phenylalanine are discussed in terms of the results obtained.", "contents": "Chorismate mutase/prephenate dehydratase from Escherichia coli K12. Binding studies with the allosteric effector phenylalanine. The binding of phenylalanine to the allosteric site of chorismate mutase/prephenate dehydratase has been studied by steady-state dialysis. Under most of the experimental conditions examined positive co-operativity was observed for the binding of ligand up to 50% saturation and negative co-operativity above 50% saturation. In the presence of 0.4 M NaCl at pH 8.2 the co-operativity was positive at all phenylalanine concentrations and the maximal stoichiometry of 1 mol of phenylalanine/mol of enzyme subunit was observed. It was concluded that there is a single phenylalanine-binding site per subunit which is associated with the regulation of each of the mutase and dehydratase activities. The effects of enzyme concentration, NaCl, temperature and pH on the binding of phenylalanine have been investigated. Neither tyrosine nor tryptophan bound to the allosteric site of the enzyme. Enzyme that was desensitized to inhibition by phenylalanine following modification of three sulphydryl groups with 5,5'-dithio-bis (2-nitrobenzoic acid) did not bind phenylalanine. The mechanism of co-operativity, the binding of the enzyme to Sepharosyl-phenylalanine and the physiological significance of the inhibition of the enzyme by phenylalanine are discussed in terms of the results obtained."}
{"id": "PMID:26564", "title": "Kinetics of the interaction of alpha-chymotrypsin with trypsin kallikrein inhibitor (Kunitz) in which the reactive-site peptide bond Lys-15--Ala-16 is split.", "content": "Modified trypsin kallikrein inhibitor (I*), with the reactive-site peptide bond Lys-15--Ala-16 split, reacts with alpha-chymotrypsin (E) via an intermediate X to the stable tetrahedral complex C:E + I  in equilibrium X leads to C. Formation X constitutes a fast pre-equilibrium (equilibrium constant Kx = 7 X 10(-5) M, association rate constant kx = 4 X 10(3)M-1s-1) to the slow reaction X leads to C (rate constant kc = 2 X 10(-3) s-1), all values at pH 7.5. No intermediate X is observed when alpha-chymotrypsin reacts with I*-OMe in which the carboxyl group of Lys-15 is esterified by methanol. This observation as well as the different pH dependence of the overall association rate constants in the case of I* and I*-OMe indicate tha formation of X precedes formation of the acyl enzyme in the catalytic pathway. The data are compared to the similar results obtained with beta-trypsin and I* or I*-OMe.", "contents": "Kinetics of the interaction of alpha-chymotrypsin with trypsin kallikrein inhibitor (Kunitz) in which the reactive-site peptide bond Lys-15--Ala-16 is split. Modified trypsin kallikrein inhibitor (I*), with the reactive-site peptide bond Lys-15--Ala-16 split, reacts with alpha-chymotrypsin (E) via an intermediate X to the stable tetrahedral complex C:E + I  in equilibrium X leads to C. Formation X constitutes a fast pre-equilibrium (equilibrium constant Kx = 7 X 10(-5) M, association rate constant kx = 4 X 10(3)M-1s-1) to the slow reaction X leads to C (rate constant kc = 2 X 10(-3) s-1), all values at pH 7.5. No intermediate X is observed when alpha-chymotrypsin reacts with I*-OMe in which the carboxyl group of Lys-15 is esterified by methanol. This observation as well as the different pH dependence of the overall association rate constants in the case of I* and I*-OMe indicate tha formation of X precedes formation of the acyl enzyme in the catalytic pathway. The data are compared to the similar results obtained with beta-trypsin and I* or I*-OMe."}
{"id": "PMID:26567", "title": "Cycloheximide causes increased accumulation of translatable mRNA for tyrosine aminotransferase and tryptophan oxygenase in livers of cortisol-treated rats.", "content": "Messenger RNA activities for two cortisol-inducible enzymes, tyrosine aminotransferase and tryptophan oxygenase, have been determined by translation in a wheat germ system. The effects of cycloheximide on the two mRNA activities have been evaluated. Cortisol leads to an increase of the translatable mRNAs for tyrosine aminotransferase and tryptophan oxygenase with a maximum at approximately 6 h. Cycloheximide was administered 4 h after treatment with cortisol; 2 h later, the activities of tyrosine aminotransferase and tryptophan oxygenase mRNA had increased five-fold and two-fold, respectively, compared to the activities reached with cortisol alone. Thereafter the amount of the two translatable mRNAs declined, though 14 h after cortisol administration the mRNA activities were still several fold higher than in control animals. Application of alpha-amanitin together with cycloheximide did not prevent an increased accumulation of specific translatable mRNAs. The increase in tyrosine aminotransferase and tryptophan oxygenase activity by cortisol was immediately blocked by cycloheximide. Whereas tryptophan oxygenase activity rapidly declined after cycloheximide application, tyrosine aminotransferase activity remained at the same level. Approximately 4 h thereafter, both enzyme activities increased again.", "contents": "Cycloheximide causes increased accumulation of translatable mRNA for tyrosine aminotransferase and tryptophan oxygenase in livers of cortisol-treated rats. Messenger RNA activities for two cortisol-inducible enzymes, tyrosine aminotransferase and tryptophan oxygenase, have been determined by translation in a wheat germ system. The effects of cycloheximide on the two mRNA activities have been evaluated. Cortisol leads to an increase of the translatable mRNAs for tyrosine aminotransferase and tryptophan oxygenase with a maximum at approximately 6 h. Cycloheximide was administered 4 h after treatment with cortisol; 2 h later, the activities of tyrosine aminotransferase and tryptophan oxygenase mRNA had increased five-fold and two-fold, respectively, compared to the activities reached with cortisol alone. Thereafter the amount of the two translatable mRNAs declined, though 14 h after cortisol administration the mRNA activities were still several fold higher than in control animals. Application of alpha-amanitin together with cycloheximide did not prevent an increased accumulation of specific translatable mRNAs. The increase in tyrosine aminotransferase and tryptophan oxygenase activity by cortisol was immediately blocked by cycloheximide. Whereas tryptophan oxygenase activity rapidly declined after cycloheximide application, tyrosine aminotransferase activity remained at the same level. Approximately 4 h thereafter, both enzyme activities increased again."}
{"id": "PMID:26570", "title": "Formation of complexes between microsomal cytochrome P-450-Fe(II) and nitrosoarenes obtained by oxidation of arylhydroxylamines or reduction of nitroarenes in situ.", "content": "A cytochrome P-450 complex exhibiting a Soret peak at 454 nm is formed by direct interaction of nitrosobenzene with NADPH-reduced rat liver microsomes in anaerobic conditions, by reaction of phenylhydroxylamine with aerobic microsomes or during nitrobenzene reduction by NADPH-reduced or dithionite-reduced microsomes. In the latter conditions, the complex formation is only transient as it is unstable to dithionite. Analogous reactions with myoglobin lead to the previously described myoglobin-Fe(II)-nitrosobenzene complex which has similar properties to those of the 454-nm-absorbing cytochrome P-450 complex. This analogy, together with the various conditions of its formation, strongly indicates that it is a cytochrome-P-450-Fe(II)-nitrosobenzene complex. The corresponding complex with the 4-chloro-nitrosobenzene ligand is formed in similar conditions. Cytochrome P-450-Fe(II) complexes with nitrosoarenes seem less stable than the previously described complexes with nitrosoalkanes.", "contents": "Formation of complexes between microsomal cytochrome P-450-Fe(II) and nitrosoarenes obtained by oxidation of arylhydroxylamines or reduction of nitroarenes in situ. A cytochrome P-450 complex exhibiting a Soret peak at 454 nm is formed by direct interaction of nitrosobenzene with NADPH-reduced rat liver microsomes in anaerobic conditions, by reaction of phenylhydroxylamine with aerobic microsomes or during nitrobenzene reduction by NADPH-reduced or dithionite-reduced microsomes. In the latter conditions, the complex formation is only transient as it is unstable to dithionite. Analogous reactions with myoglobin lead to the previously described myoglobin-Fe(II)-nitrosobenzene complex which has similar properties to those of the 454-nm-absorbing cytochrome P-450 complex. This analogy, together with the various conditions of its formation, strongly indicates that it is a cytochrome-P-450-Fe(II)-nitrosobenzene complex. The corresponding complex with the 4-chloro-nitrosobenzene ligand is formed in similar conditions. Cytochrome P-450-Fe(II) complexes with nitrosoarenes seem less stable than the previously described complexes with nitrosoalkanes."}
{"id": "PMID:26572", "title": "Neurotransmittor changes in the rat brain after portacaval anastomosis.", "content": "Portacaval anastomosis in rats elevated the brain serotonin content by about 30%, the greatest increase being noted in the brain stem. A minor increase in norepinephrine content but no change in dopamine concentration was also noted. Low dose L-dopa treatment reversed the serotonin changes but did not affect catecholamine concentrations. Protein load tended to lower most transmittor concentrations without clinically affecting the animals. The formation of 5-HT from tryptophane in vitro in rat cortical slices was reduced by about 35% whereas the formation of 5-HIAA in the same slices was increased with about 60%. This in vitro study indicates a change in the activity of serotonin neurons caused by the protacaval shunt. The findings suggest that changes in brain serotonin metabolism and brain serotonin neurons may be an explanation of hepatic encephalopathy.", "contents": "Neurotransmittor changes in the rat brain after portacaval anastomosis. Portacaval anastomosis in rats elevated the brain serotonin content by about 30%, the greatest increase being noted in the brain stem. A minor increase in norepinephrine content but no change in dopamine concentration was also noted. Low dose L-dopa treatment reversed the serotonin changes but did not affect catecholamine concentrations. Protein load tended to lower most transmittor concentrations without clinically affecting the animals. The formation of 5-HT from tryptophane in vitro in rat cortical slices was reduced by about 35% whereas the formation of 5-HIAA in the same slices was increased with about 60%. This in vitro study indicates a change in the activity of serotonin neurons caused by the protacaval shunt. The findings suggest that changes in brain serotonin metabolism and brain serotonin neurons may be an explanation of hepatic encephalopathy."}
{"id": "PMID:26573", "title": "Effect of capsule colour and order of administration of hypnotic treatments.", "content": "Ninety-six hospitalized insomniac patients were asked to compare by a daily questionnaire the effect on sleep of the colour of the capsules and the order of administration of two treatments--heptabarbital and placebo. A balanced incomplete-block design was used; sleep onset time and sleep duration time were the main criteria of assessment. There was a significant interaction of colour and order of administration with sex. The placebo response was positive in 36% of instances.", "contents": "Effect of capsule colour and order of administration of hypnotic treatments. Ninety-six hospitalized insomniac patients were asked to compare by a daily questionnaire the effect on sleep of the colour of the capsules and the order of administration of two treatments--heptabarbital and placebo. A balanced incomplete-block design was used; sleep onset time and sleep duration time were the main criteria of assessment. There was a significant interaction of colour and order of administration with sex. The placebo response was positive in 36% of instances."}
{"id": "PMID:26575", "title": "Subpopulations of mouse T lymphocytes. II. Suppression of graft-vs.-host reactions by naturally proliferating splenic T cells.", "content": "The immunological role of a naturally proliferating subpopulation of splenic T cells was investigated using the graft-vs.-host (GvH) reaction on the mouse. Normal parental spleen cells, purified splenic T cells or lymph node cells were pulse-treated for one hour in vitro with tritiated thymidine of high specific activity ([3H]dThd, \"thymidine suicide\"). The treatment specifically and selectively kills proliferating cells which are actively synthesizing DNA, i.e. cells in S phase. Following treatment, the cells were transferred to F1 recipients and the GvH reaction measured by the splenomegaly assay. The results showed that the GvH effector cells in the donor spleen and lymph node are nonproliferating T cells. Furthermore, donor spleen cells treated with [3H]dThd consistently had enhanced GvH reactivity when compared to the controls, while the phytohemagglutinin response of these same treated cell suspensions was significantly inhibited. When purified splenic T cells were used, treatment with [3H]dThd also caused an increase in the GvH reaction, showing that a T cell population was being affected by the cycleactive agent. These results indicated that some naturally proliferating T cells have suppressor functions, and their specific inactivation allows nonproliferating effector T cells to mount a more vigourous GvH reaction.", "contents": "Subpopulations of mouse T lymphocytes. II. Suppression of graft-vs.-host reactions by naturally proliferating splenic T cells. The immunological role of a naturally proliferating subpopulation of splenic T cells was investigated using the graft-vs.-host (GvH) reaction on the mouse. Normal parental spleen cells, purified splenic T cells or lymph node cells were pulse-treated for one hour in vitro with tritiated thymidine of high specific activity ([3H]dThd, \"thymidine suicide\"). The treatment specifically and selectively kills proliferating cells which are actively synthesizing DNA, i.e. cells in S phase. Following treatment, the cells were transferred to F1 recipients and the GvH reaction measured by the splenomegaly assay. The results showed that the GvH effector cells in the donor spleen and lymph node are nonproliferating T cells. Furthermore, donor spleen cells treated with [3H]dThd consistently had enhanced GvH reactivity when compared to the controls, while the phytohemagglutinin response of these same treated cell suspensions was significantly inhibited. When purified splenic T cells were used, treatment with [3H]dThd also caused an increase in the GvH reaction, showing that a T cell population was being affected by the cycleactive agent. These results indicated that some naturally proliferating T cells have suppressor functions, and their specific inactivation allows nonproliferating effector T cells to mount a more vigourous GvH reaction."}
{"id": "PMID:26576", "title": "Investigation of cardiac beta-adrenoceptors using 125I-labelled 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol.", "content": "1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol (IIP) is a potent beta-adrenergic antagonist which has been labelled to high specific activity with 125I and used to bind to rat myocardial membranes. The characteristics of binding were consistent with the known properties of beta-receptors. Thus, binding was highly stereospecific for the L-stereoisomer since L-propranolol was two orders of magnitude more potent than the D-isomer in competing for these sites. The beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine competed for binding with potencies paralleling their pharmacological potencies as beta-adrenergic effectors. The dissociation constant for binding of IIP was 4--5 nM as measured either by direct binding studies or by its inhibition of isoproterenol stimulated adenylate cyclase. Binding was saturable with 0.06 pmoles of IIP per mg of membrane protein binding at saturation. 125IIP is a high affinity, high specific activity ligand suitable for use as a selective probe for the detection and quantitation of cardiac beta-receptors. Its introduction should help solve the problems involved in the investigation of myocardial beta-adrenergic receptors.", "contents": "Investigation of cardiac beta-adrenoceptors using 125I-labelled 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol. 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol (IIP) is a potent beta-adrenergic antagonist which has been labelled to high specific activity with 125I and used to bind to rat myocardial membranes. The characteristics of binding were consistent with the known properties of beta-receptors. Thus, binding was highly stereospecific for the L-stereoisomer since L-propranolol was two orders of magnitude more potent than the D-isomer in competing for these sites. The beta-adrenergic agonists isoproterenol, epinephrine and norepinephrine competed for binding with potencies paralleling their pharmacological potencies as beta-adrenergic effectors. The dissociation constant for binding of IIP was 4--5 nM as measured either by direct binding studies or by its inhibition of isoproterenol stimulated adenylate cyclase. Binding was saturable with 0.06 pmoles of IIP per mg of membrane protein binding at saturation. 125IIP is a high affinity, high specific activity ligand suitable for use as a selective probe for the detection and quantitation of cardiac beta-receptors. Its introduction should help solve the problems involved in the investigation of myocardial beta-adrenergic receptors."}
{"id": "PMID:26577", "title": "Benzodiazepines: potentiation of a GABA inhibitory response in the dorsal raphe nucleus.", "content": "Based on evidence that the dorsal raphe nucleus (DR) has specific and independent receptors for 5HT, GABA and glycine (Gallager and Aghajanian, 1976; Wang and Aghajanian, 1977), alterations in the firing rate of DR neurons following the administration of benzodiazepines (BZ) were evaluated to determine whether they were the result of a direct interaction with 5HT receptors or due to interactions of these drugs with GABA and/or glycine. The effects of BZs after both direct and systemic application were tested in rats using microiotophoretic and single-cell recording techniques. Although the BZs did not alter the spontaneous firing rate of the DR, both the systemic and iontophoretic administration of these drugs were found to potentiate the inhibitory response produced by GABA. The data suggest that this potentiation is mediated postsynaptically. Since the effects of BZs on the spontaneous activity of the DR are only apparent following pretreatments with AOAA, it is speculated that these drugs may only have pronounced effects when GABAergic input is prominent.", "contents": "Benzodiazepines: potentiation of a GABA inhibitory response in the dorsal raphe nucleus. Based on evidence that the dorsal raphe nucleus (DR) has specific and independent receptors for 5HT, GABA and glycine (Gallager and Aghajanian, 1976; Wang and Aghajanian, 1977), alterations in the firing rate of DR neurons following the administration of benzodiazepines (BZ) were evaluated to determine whether they were the result of a direct interaction with 5HT receptors or due to interactions of these drugs with GABA and/or glycine. The effects of BZs after both direct and systemic application were tested in rats using microiotophoretic and single-cell recording techniques. Although the BZs did not alter the spontaneous firing rate of the DR, both the systemic and iontophoretic administration of these drugs were found to potentiate the inhibitory response produced by GABA. The data suggest that this potentiation is mediated postsynaptically. Since the effects of BZs on the spontaneous activity of the DR are only apparent following pretreatments with AOAA, it is speculated that these drugs may only have pronounced effects when GABAergic input is prominent."}
{"id": "PMID:26578", "title": "2,5-Dimethoxy-4-methylamphetamine (DOM)- a central component of its cardiovascular effects in rats; involvement of serotonin.", "content": "The hallucinogen DOM produces a rise in blood pressure and heart rate when injected into the cerebral ventricles of anesthetized rats. These effects are abolished in rats with transected spinal cords but are unaffected by prior treatment with hexamethonium. Central but not peripheral administration of the serotonin antagonist BOL reduces the response. Tachyphylaxis to the response develops rapidly and is accompanied by a decrease in the ability of 5-HT to induce a centrally mediated cardiovascular change. It is concluded that the response is mediated by direct stimulation of central 5HT receptors. Tachyphylaxis may be the result of irreversible binding of DOM to 5-HT receptors or to 5-HT receptor densensitization.", "contents": "2,5-Dimethoxy-4-methylamphetamine (DOM)- a central component of its cardiovascular effects in rats; involvement of serotonin. The hallucinogen DOM produces a rise in blood pressure and heart rate when injected into the cerebral ventricles of anesthetized rats. These effects are abolished in rats with transected spinal cords but are unaffected by prior treatment with hexamethonium. Central but not peripheral administration of the serotonin antagonist BOL reduces the response. Tachyphylaxis to the response develops rapidly and is accompanied by a decrease in the ability of 5-HT to induce a centrally mediated cardiovascular change. It is concluded that the response is mediated by direct stimulation of central 5HT receptors. Tachyphylaxis may be the result of irreversible binding of DOM to 5-HT receptors or to 5-HT receptor densensitization."}
{"id": "PMID:26579", "title": "Biphasic effect of chlorpromazine on rat paradoxical sleep: a study of dose-related mechanisms.", "content": "The experiments reported here investigated the effect of chlorpromazine (CPZ) alone or after inhibition of catecholamine (CA) synthesis on paradoxical sleep (PS) in the rat. The dose--response curve for CPZ was biphasic with enhancement of PS after low doses, and depression of PS after higher doses. In contrast, low doses of CPZ after inhibition of CA synthesis markedly decreased PS. This decrease was greater after tyrosine hydroxylase inhibition than after dopamine-beta-hydroxylase inhibition. These results support the view that low doses of CPZ produce increased activity in brain CA synapses, and that both dopamine and noradrenaline participate in the control of PS in the rat.", "contents": "Biphasic effect of chlorpromazine on rat paradoxical sleep: a study of dose-related mechanisms. The experiments reported here investigated the effect of chlorpromazine (CPZ) alone or after inhibition of catecholamine (CA) synthesis on paradoxical sleep (PS) in the rat. The dose--response curve for CPZ was biphasic with enhancement of PS after low doses, and depression of PS after higher doses. In contrast, low doses of CPZ after inhibition of CA synthesis markedly decreased PS. This decrease was greater after tyrosine hydroxylase inhibition than after dopamine-beta-hydroxylase inhibition. These results support the view that low doses of CPZ produce increased activity in brain CA synapses, and that both dopamine and noradrenaline participate in the control of PS in the rat."}
{"id": "PMID:26580", "title": "Studies on the mechanism of the vasodilator effects of prazosin in dogs and rabbits.", "content": "In pentobarbital (35.0 mg/kg) anaesthetised dogs, bolus injections of prazosin into the femoral artery (3.0--300.0 microgram) provoked a dose-related fall in the vascular resistance of the innervated hind limb. In contrast to papaverine, prazosin failed to produce the same effect in dogs under spinal anaesthesia even when the intrinsic femoral vascular tone was increased with vasopressin. However, vasodilator effects of prazosin were again observed when the tone of the limb was elevated by either stimulating the sympathetic lumbar chain or by infusing alpha-adrenoceptor agonists. A significant reduction of both aortic blood pressure and pressor response to bilateral carotid artery occlusion was noted in a group of normotensive dogs anaesthetised 12 h after the last dose of prazosin given twice daily at 0.5 mg/kg, p.o., for 3 day period. This short-term treatment modified neither the resting heart rate nor the positive chronotropic effect induced by either intravenous noradrenaline or electrical stimulation of pre- and post-ganglionic nerve fibres of the right stellate ganglion. However, it prevented the larger increase in heart rate in response to bilateral carotid occlusion in placebo-treated dogs after section of the vagi. A decrease in baseline sympathetic tone of the perfused hind limb as well as vasoconstrictor effects produced by i.a. injections of several alpha-adrenoceptor agonists and electrical stimulation of the lumbar sympathetic chain was observed in prazosin-treated animals. The dose--pressor response profiles to these alpha-adrenoceptor stimulants after prazosin were not parallel to those obtained in the control group. The vasoconstrictor response to angiotensin II was not changed by prazosin. In rabbit aortic strips, prazosin (0.1--3.0 micrometer) produced competitive antagonism of the contractile responses induced by cirazoline, noradrenaline and phenylephrine. In contrast to papaverine, prazosin in concentrations up to 100.0 micrometer neither relaxed the aortic strips contracted by potassium ions nor modified the concentration-response curve to calcium ions. These studies indicate that blood pressure lowering effects of prazosin given acutely or for three days can be accounted for by a clear-cut functional impairment of vascular postsynaptic alpha-adrenoceptors. No evidence for a direct myorelaxant property of prazosin could be obtained in these studies.", "contents": "Studies on the mechanism of the vasodilator effects of prazosin in dogs and rabbits. In pentobarbital (35.0 mg/kg) anaesthetised dogs, bolus injections of prazosin into the femoral artery (3.0--300.0 microgram) provoked a dose-related fall in the vascular resistance of the innervated hind limb. In contrast to papaverine, prazosin failed to produce the same effect in dogs under spinal anaesthesia even when the intrinsic femoral vascular tone was increased with vasopressin. However, vasodilator effects of prazosin were again observed when the tone of the limb was elevated by either stimulating the sympathetic lumbar chain or by infusing alpha-adrenoceptor agonists. A significant reduction of both aortic blood pressure and pressor response to bilateral carotid artery occlusion was noted in a group of normotensive dogs anaesthetised 12 h after the last dose of prazosin given twice daily at 0.5 mg/kg, p.o., for 3 day period. This short-term treatment modified neither the resting heart rate nor the positive chronotropic effect induced by either intravenous noradrenaline or electrical stimulation of pre- and post-ganglionic nerve fibres of the right stellate ganglion. However, it prevented the larger increase in heart rate in response to bilateral carotid occlusion in placebo-treated dogs after section of the vagi. A decrease in baseline sympathetic tone of the perfused hind limb as well as vasoconstrictor effects produced by i.a. injections of several alpha-adrenoceptor agonists and electrical stimulation of the lumbar sympathetic chain was observed in prazosin-treated animals. The dose--pressor response profiles to these alpha-adrenoceptor stimulants after prazosin were not parallel to those obtained in the control group. The vasoconstrictor response to angiotensin II was not changed by prazosin. In rabbit aortic strips, prazosin (0.1--3.0 micrometer) produced competitive antagonism of the contractile responses induced by cirazoline, noradrenaline and phenylephrine. In contrast to papaverine, prazosin in concentrations up to 100.0 micrometer neither relaxed the aortic strips contracted by potassium ions nor modified the concentration-response curve to calcium ions. These studies indicate that blood pressure lowering effects of prazosin given acutely or for three days can be accounted for by a clear-cut functional impairment of vascular postsynaptic alpha-adrenoceptors. No evidence for a direct myorelaxant property of prazosin could be obtained in these studies."}
{"id": "PMID:26581", "title": "Positive chronotropic and inotropic responses to guanosine in the isolated dog atrium.", "content": "The effects of guanosine on chronotropism and inotropism in isolated dog atria were studied in spontaneously beating preparations which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized support dog. Guanosine administered into the cannulated sinus node artery in a dose range of 30 microgram to 3 mg produced a dose-related positive inotropic and chronotropic effect. The positive responses to guanosine were not inhibited by treatment with propranolol or a non-depressant beta-blocker, carteolol, in doses which blocked responses to norepinephrine. From these results, it is concluded that guanosine has a direct effect on atrial rate and contractility.", "contents": "Positive chronotropic and inotropic responses to guanosine in the isolated dog atrium. The effects of guanosine on chronotropism and inotropism in isolated dog atria were studied in spontaneously beating preparations which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized support dog. Guanosine administered into the cannulated sinus node artery in a dose range of 30 microgram to 3 mg produced a dose-related positive inotropic and chronotropic effect. The positive responses to guanosine were not inhibited by treatment with propranolol or a non-depressant beta-blocker, carteolol, in doses which blocked responses to norepinephrine. From these results, it is concluded that guanosine has a direct effect on atrial rate and contractility."}
{"id": "PMID:26584", "title": "Graft versus leukemia. VIII. Selective reduction in antihost reactivity without loss of antileukemic reactivity by treatment of donor mice with lipopolysaccharide.", "content": "Spleen and lymph node cells from DBA/2 (H-2d) donor mice treated with multiple injections of bacterial lipopolysaccharide (LPS) were tested in vivo for reactivity against normal tissues of host AKR (H-2k) mice against an AKR long-passage, acute lymphoblastic leukemia (BW5147). LPS treatment of donor mice resulted in a reduction in graft-versus-host (GVH) reactivity without loss of graft-versus-leukemia (GVL) reactivity. Immunocompetent cells from LPS treated DBA/2 donors were effective when used for adoptive immunotherapy (in combination with chemoradiotherapy) of BW5147 leukemia. GVH associated mortality decreased as the dose of spleen cells from LPS treated histoincompatible donors was increased as much as four times the number necessary to eliminate leukemia. The mechanism by which LPS reduced GVH reactivity without eliminating GVL reactivity is unclear; however, it does not appear to be the result of a dilution in the number of GVH reactive cells by nonlymphoid elements in the donor spleen nor of the adjuvant effects of LPS on resistance to bacterial infections.", "contents": "Graft versus leukemia. VIII. Selective reduction in antihost reactivity without loss of antileukemic reactivity by treatment of donor mice with lipopolysaccharide. Spleen and lymph node cells from DBA/2 (H-2d) donor mice treated with multiple injections of bacterial lipopolysaccharide (LPS) were tested in vivo for reactivity against normal tissues of host AKR (H-2k) mice against an AKR long-passage, acute lymphoblastic leukemia (BW5147). LPS treatment of donor mice resulted in a reduction in graft-versus-host (GVH) reactivity without loss of graft-versus-leukemia (GVL) reactivity. Immunocompetent cells from LPS treated DBA/2 donors were effective when used for adoptive immunotherapy (in combination with chemoradiotherapy) of BW5147 leukemia. GVH associated mortality decreased as the dose of spleen cells from LPS treated histoincompatible donors was increased as much as four times the number necessary to eliminate leukemia. The mechanism by which LPS reduced GVH reactivity without eliminating GVL reactivity is unclear; however, it does not appear to be the result of a dilution in the number of GVH reactive cells by nonlymphoid elements in the donor spleen nor of the adjuvant effects of LPS on resistance to bacterial infections."}
{"id": "PMID:26587", "title": "Acid release at meiotic maturation of oocytes in the polychaete annelid Sabellaria alveolata.", "content": "ABout 1 pmole of acid per egg is released when prophasic oocytes undergo maturation under the action of sperm, proteases or ionophore A 23187. No similar acid release occurs at fertilization of matured oocytes. These findings are compared with data on Urechis and sea urchin.", "contents": "Acid release at meiotic maturation of oocytes in the polychaete annelid Sabellaria alveolata. ABout 1 pmole of acid per egg is released when prophasic oocytes undergo maturation under the action of sperm, proteases or ionophore A 23187. No similar acid release occurs at fertilization of matured oocytes. These findings are compared with data on Urechis and sea urchin."}
{"id": "PMID:26588", "title": "[Effect of tropaphene and fentolamin on the spasmogenic effects of adrenaline, noradrenaline, serotonin and other biologically active substances].", "content": "Tests conducted in vitro and in vivo demonstrated that tropaphen, tropine ether of alpha-phenyl-beta-(p-acetoxyphenyl)-propionic acid, an original alpha-adrenoblocking agent, display a marked antiserotonin activity exceeding that of phentolamine. Moreover, tropaphen is more active that phenolamine by its inhibiting influence on the spasmogenous effects of histamine, angiotensin, bradykinine and prostaglandin E2. In doses of 0.1 and 0.25 mg/kg both drugs had no effect on changes of the arterial pressure in anesthetized rats, caused by the above mentioned biologically active substances.", "contents": "[Effect of tropaphene and fentolamin on the spasmogenic effects of adrenaline, noradrenaline, serotonin and other biologically active substances]. Tests conducted in vitro and in vivo demonstrated that tropaphen, tropine ether of alpha-phenyl-beta-(p-acetoxyphenyl)-propionic acid, an original alpha-adrenoblocking agent, display a marked antiserotonin activity exceeding that of phentolamine. Moreover, tropaphen is more active that phenolamine by its inhibiting influence on the spasmogenous effects of histamine, angiotensin, bradykinine and prostaglandin E2. In doses of 0.1 and 0.25 mg/kg both drugs had no effect on changes of the arterial pressure in anesthetized rats, caused by the above mentioned biologically active substances."}
{"id": "PMID:26589", "title": "[Comparative assessment of the effect of sympatholytics and beta-adrenoblockaders on carbohydrate-phosphorus metabolic indices in the myocardium of growing rats].", "content": "The sympatholyitic ornide and beta-adrenoblocking agent alpheprol were introduced intraperitoneally in single doses of 5 and 1 mg/kg, respectively to 7--30 day and 3--5-month old adult rats. The content of ATP, ADP, AMP, inorganic phosphorus glycogen and also active P32 incorporation were determined. The 7-day old rattlings are shown to be more sensitive to ornide than to alpheprol by comparison with older animals.", "contents": "[Comparative assessment of the effect of sympatholytics and beta-adrenoblockaders on carbohydrate-phosphorus metabolic indices in the myocardium of growing rats]. The sympatholyitic ornide and beta-adrenoblocking agent alpheprol were introduced intraperitoneally in single doses of 5 and 1 mg/kg, respectively to 7--30 day and 3--5-month old adult rats. The content of ATP, ADP, AMP, inorganic phosphorus glycogen and also active P32 incorporation were determined. The 7-day old rattlings are shown to be more sensitive to ornide than to alpheprol by comparison with older animals."}
{"id": "PMID:26591", "title": "[Metabolic effects of ethyl alcohol the ways to correct them].", "content": "Tests conducted on albino male-rats demonstrated that with its intragastric administration in a dose of 3 g/kg ethanol produces a hypoxy-like situation in the organism, i.e. the oxygen tension in the liver and skeletal muscles decreases and the redox potential is activation during the 1st hour with succinate-cytochrome-c-oxidase of the liver mitochondria with concomitantly activated oxidation of succinic acid. The activity of NAD-dependent dehydrogenases goes down and in the blood occur acidotic shifts in the acid-base equilibrium (ABE). Twenty four hours after a single administration of ethanol the activity of all the study liver enzymes declines with the acidotic ABE shifts remaining unchanged. The used mixture of glutamate and sodium succinate appreciably decreases the blood ethanol level, corrects metabolic effects of ethanol and increases the survival of rats receiving lethal doses of ethanol.", "contents": "[Metabolic effects of ethyl alcohol the ways to correct them]. Tests conducted on albino male-rats demonstrated that with its intragastric administration in a dose of 3 g/kg ethanol produces a hypoxy-like situation in the organism, i.e. the oxygen tension in the liver and skeletal muscles decreases and the redox potential is activation during the 1st hour with succinate-cytochrome-c-oxidase of the liver mitochondria with concomitantly activated oxidation of succinic acid. The activity of NAD-dependent dehydrogenases goes down and in the blood occur acidotic shifts in the acid-base equilibrium (ABE). Twenty four hours after a single administration of ethanol the activity of all the study liver enzymes declines with the acidotic ABE shifts remaining unchanged. The used mixture of glutamate and sodium succinate appreciably decreases the blood ethanol level, corrects metabolic effects of ethanol and increases the survival of rats receiving lethal doses of ethanol."}
{"id": "PMID:26594", "title": "[Ethological analysis of the action of medazepam and diazepam on the zoosocial behavior of isolated mice].", "content": "Tests set up with isolated mice of two groups (aggressive and \"fearful\") evidenced that diazepam and medazepam weaken the behavioral manifestations of the partner's avoidance, increase sociability in \"fearful\" mice and help to regain the ability for elementary intraspecies contacts. These drugs have a biphasic action on the behavior of aggressive mice, small doses (medazepam 0.1 mg/kg) facilitating aggression and large one (medazepam, diazepam--5 mg/kg) suppressing it.", "contents": "[Ethological analysis of the action of medazepam and diazepam on the zoosocial behavior of isolated mice]. Tests set up with isolated mice of two groups (aggressive and \"fearful\") evidenced that diazepam and medazepam weaken the behavioral manifestations of the partner's avoidance, increase sociability in \"fearful\" mice and help to regain the ability for elementary intraspecies contacts. These drugs have a biphasic action on the behavior of aggressive mice, small doses (medazepam 0.1 mg/kg) facilitating aggression and large one (medazepam, diazepam--5 mg/kg) suppressing it."}
{"id": "PMID:26590", "title": "[Effect of a new central adrenolytic on cardiac metabolic indices in neurogenic damage].", "content": "It is shown that in rabbits subjected to an electric stimulation of the aortic arch there developed concurrently with depletion of tissular norepinephrine reserves in the myocardium also gross metabolic disorders. A preliminary introduction of the drug izm-611 by blocking central alpha-adrenoreseptors at the same time prevented depletion of the tissular norepinephrine reserves and development of disturbances of the energy exchange in the myocardium caused by its neurogenic damage.", "contents": "[Effect of a new central adrenolytic on cardiac metabolic indices in neurogenic damage]. It is shown that in rabbits subjected to an electric stimulation of the aortic arch there developed concurrently with depletion of tissular norepinephrine reserves in the myocardium also gross metabolic disorders. A preliminary introduction of the drug izm-611 by blocking central alpha-adrenoreseptors at the same time prevented depletion of the tissular norepinephrine reserves and development of disturbances of the energy exchange in the myocardium caused by its neurogenic damage."}
{"id": "PMID:26595", "title": "[Action of analeptics in acute alcoholic intoxication].", "content": "Tests conducted on rabbits in a state of acute ethanol poisoning (2.5 g/kg per os) of a medium degree demonstrated that caffein (10 mg/kg) and bemegride (5 mg/kg) introduced one time intravenously at the height of alcoholic intoxication raise the activity of aerobic oxidative processes, but fail to eliminate metabolic acidosis and do not accelerate the excretion of ethanol. Unlike caffein, bemegride shows a tendency toward respiratory compensation of metabolic acidosis and lowers the activity of the alcohol-dehydrogenase.", "contents": "[Action of analeptics in acute alcoholic intoxication]. Tests conducted on rabbits in a state of acute ethanol poisoning (2.5 g/kg per os) of a medium degree demonstrated that caffein (10 mg/kg) and bemegride (5 mg/kg) introduced one time intravenously at the height of alcoholic intoxication raise the activity of aerobic oxidative processes, but fail to eliminate metabolic acidosis and do not accelerate the excretion of ethanol. Unlike caffein, bemegride shows a tendency toward respiratory compensation of metabolic acidosis and lowers the activity of the alcohol-dehydrogenase."}
{"id": "PMID:26596", "title": "[Pharmacokinetics of the new Soviet, tritium-labelled, antihistamine preparation, phencarol].", "content": "As evidenced no less than 45 per cent of tritium-labelled antihistaminic drug phencarol (quinuclidine-3-diphenylcarbinol hydrochloride) introduced intragastrically to rats is absorbed. The maximal radioactivity in various organs is reached in 1--3 hours, with high specific radioactivity being recorded in the lungs and liver and low--in the brain. The drug or radioactive products of its tranformation are eliminated largely via the gastrointestinal tract and kidneys.", "contents": "[Pharmacokinetics of the new Soviet, tritium-labelled, antihistamine preparation, phencarol]. As evidenced no less than 45 per cent of tritium-labelled antihistaminic drug phencarol (quinuclidine-3-diphenylcarbinol hydrochloride) introduced intragastrically to rats is absorbed. The maximal radioactivity in various organs is reached in 1--3 hours, with high specific radioactivity being recorded in the lungs and liver and low--in the brain. The drug or radioactive products of its tranformation are eliminated largely via the gastrointestinal tract and kidneys."}
{"id": "PMID:26597", "title": "[Effect of amisyl and spasmolytin on the blood supply and oxygen metabolism of the brain].", "content": "The effect of benactyzine and spasmolytin adiphenine on the blood circulation in the oxygen consumption by the brain were investigated in experiments on dogs. The resulting data point to a biphasic action of benacyzine and spasmolytin on the blood supply of the brain (after a short-lived increase of the blood flow a clearcut decline of it is noted). The oxygen intake from the blood varies irregularly. In chlorophos-poisoned dogs the oxygen absorption by the brain changes under the effect of benactyzine and rises after administration of spasmolytin. The cerebral circulation then changes non-uniformly under the effect of benactyzine, while following spasmolytin injections it dicreases in the majority of experiments.", "contents": "[Effect of amisyl and spasmolytin on the blood supply and oxygen metabolism of the brain]. The effect of benactyzine and spasmolytin adiphenine on the blood circulation in the oxygen consumption by the brain were investigated in experiments on dogs. The resulting data point to a biphasic action of benacyzine and spasmolytin on the blood supply of the brain (after a short-lived increase of the blood flow a clearcut decline of it is noted). The oxygen intake from the blood varies irregularly. In chlorophos-poisoned dogs the oxygen absorption by the brain changes under the effect of benactyzine and rises after administration of spasmolytin. The cerebral circulation then changes non-uniformly under the effect of benactyzine, while following spasmolytin injections it dicreases in the majority of experiments."}
{"id": "PMID:26598", "title": "[Possible neuropharmacological regulation of chemical carcinogenesis caused by diethylnitrosamine].", "content": "The effect of a number of neurotropic drugs on diethylnitrosoamine (DENA)-induced chemical carcinogenesis was studied by applying pharmacological, morphological and biochemical techniques. Atropine stimulated significantly the rat liver and esophagus carcinogenesis, whereas the alpha-adrenoblocking agent, a pyrrhoxane analogue, and, particularly, proserine inhibited these processes. All animals treated with DENA demonstrated a significant increase of liver mitochondrial monoaminoxidase activity. These findings as well as the evidence of a stimulating effect of exogenous norepinephrine on carcionogenesis, together with the literature sources on carcinogenic and modifying carcinogenesis action of neurotropics allow the authors to formulate a concet of the trigger role played by catecholamines in the DENA-induced cell transformation and carcinogenesis.", "contents": "[Possible neuropharmacological regulation of chemical carcinogenesis caused by diethylnitrosamine]. The effect of a number of neurotropic drugs on diethylnitrosoamine (DENA)-induced chemical carcinogenesis was studied by applying pharmacological, morphological and biochemical techniques. Atropine stimulated significantly the rat liver and esophagus carcinogenesis, whereas the alpha-adrenoblocking agent, a pyrrhoxane analogue, and, particularly, proserine inhibited these processes. All animals treated with DENA demonstrated a significant increase of liver mitochondrial monoaminoxidase activity. These findings as well as the evidence of a stimulating effect of exogenous norepinephrine on carcionogenesis, together with the literature sources on carcinogenic and modifying carcinogenesis action of neurotropics allow the authors to formulate a concet of the trigger role played by catecholamines in the DENA-induced cell transformation and carcinogenesis."}
{"id": "PMID:26606", "title": "The pathophysiology of hyperprolactinemic states and the role of newer ergot compounds in their treatment.", "content": "Studies of prolactin secretion in humans have confirmed the concept, derived originally from animal investigations, that prolactin is predominantly controlled by tonic inhibition from the hypothalamus. The locus of action of dopamine and dopaminergic agents such as the ergot alkaloids inhibiting prolactin secretion appears to be primarily at the pituitary level, though a hypothalamic action to increase secretion of prolactin inhibitory factor may also contribute. Prolactin hypersecretion, through any of several possible mechanisms, is frequently but not always found in patients with galactorrhea. Recent studies have shown that hyperprolactinemia is considerably more common than was previously appreciated among patients without galactorrhea. It is present in at least two-thirds of all patients with pituitary tumors and in a significant minority of patients with secondary amenorrhea. Its clinical measurement in these conditions is therefore of considerable diagnostic importance. Whatever the pathophysiology of its production, hyperprolactinemia of all forms is responsive to treatment with the newer ergot alkaloids. The potential use of these agents for therapeutic purposes, particularly in the treatment of infertility, appears to be wider than was originally anticipated.", "contents": "The pathophysiology of hyperprolactinemic states and the role of newer ergot compounds in their treatment. Studies of prolactin secretion in humans have confirmed the concept, derived originally from animal investigations, that prolactin is predominantly controlled by tonic inhibition from the hypothalamus. The locus of action of dopamine and dopaminergic agents such as the ergot alkaloids inhibiting prolactin secretion appears to be primarily at the pituitary level, though a hypothalamic action to increase secretion of prolactin inhibitory factor may also contribute. Prolactin hypersecretion, through any of several possible mechanisms, is frequently but not always found in patients with galactorrhea. Recent studies have shown that hyperprolactinemia is considerably more common than was previously appreciated among patients without galactorrhea. It is present in at least two-thirds of all patients with pituitary tumors and in a significant minority of patients with secondary amenorrhea. Its clinical measurement in these conditions is therefore of considerable diagnostic importance. Whatever the pathophysiology of its production, hyperprolactinemia of all forms is responsive to treatment with the newer ergot alkaloids. The potential use of these agents for therapeutic purposes, particularly in the treatment of infertility, appears to be wider than was originally anticipated."}
{"id": "PMID:26609", "title": "Evaluation of testicular function in prepubertal boys by means of the luteinizing hormone-releasing hormone test.", "content": "Luteinizing hormone (LH)-releasing hormone (LH-RH) tests (50 microgram/sq m intravenously) were performed in 112 prepubertal boys ages 13/12 to 11 years (mean +/- standard deviation, 75/12 +/- 16/12 years) suspected of having a testicular disorder because of improperly located testes (77 boys) or hypogonadism (35 boys). Four of the patients were retested within a period ranging from 6 to 16 months. Of the 112 boys tested, 17% were found to have high basal levels of follicle-stimulating hormone (FSH) and 23% were found to have an abnormally high release of FSH after LH-RH administration. Only three patients had abnormally high basal levels of LH and/or elevated LH responses to LH-RH. The basal plasma testosterone levels were found to be normal in all 112 bosy. The fact that plasma FSH levels were elevated more often than LH levels suggests that the tubular elements are damaged more frequently than are the Leydig cells. The surprisingly high incidence of an abnormal response of plasma FSH to LH-RH in boys with mobile testes calls for an increased awareness of the importance of regular examination of these patients until full puberty has been achieved. It is concluded that determination of basal plasma FSH levels and the response to LH-RH stimulation is a useful diagnostic tool for evaluating testicular function in prepubertal boys with suspected pathology of the testes.", "contents": "Evaluation of testicular function in prepubertal boys by means of the luteinizing hormone-releasing hormone test. Luteinizing hormone (LH)-releasing hormone (LH-RH) tests (50 microgram/sq m intravenously) were performed in 112 prepubertal boys ages 13/12 to 11 years (mean +/- standard deviation, 75/12 +/- 16/12 years) suspected of having a testicular disorder because of improperly located testes (77 boys) or hypogonadism (35 boys). Four of the patients were retested within a period ranging from 6 to 16 months. Of the 112 boys tested, 17% were found to have high basal levels of follicle-stimulating hormone (FSH) and 23% were found to have an abnormally high release of FSH after LH-RH administration. Only three patients had abnormally high basal levels of LH and/or elevated LH responses to LH-RH. The basal plasma testosterone levels were found to be normal in all 112 bosy. The fact that plasma FSH levels were elevated more often than LH levels suggests that the tubular elements are damaged more frequently than are the Leydig cells. The surprisingly high incidence of an abnormal response of plasma FSH to LH-RH in boys with mobile testes calls for an increased awareness of the importance of regular examination of these patients until full puberty has been achieved. It is concluded that determination of basal plasma FSH levels and the response to LH-RH stimulation is a useful diagnostic tool for evaluating testicular function in prepubertal boys with suspected pathology of the testes."}
{"id": "PMID:26611", "title": "[Modulation of autonomic correlates of emotional stress and adaptive responses].", "content": "The character and dynamics of the cardio-vascular response to psychogenic stress (confrontation of cat and dog) depends on active or passive type of behavioral response. Tranquilizers inhibit long-lasting hypertension otherwise occurring after the stress stimulus. Adaptive cardio-vascular responses and baroreceptor reflexes did not alter after tranquilizers administration. Effects of psychotropic drugs correspond to the type of individual behavioral response.", "contents": "[Modulation of autonomic correlates of emotional stress and adaptive responses]. The character and dynamics of the cardio-vascular response to psychogenic stress (confrontation of cat and dog) depends on active or passive type of behavioral response. Tranquilizers inhibit long-lasting hypertension otherwise occurring after the stress stimulus. Adaptive cardio-vascular responses and baroreceptor reflexes did not alter after tranquilizers administration. Effects of psychotropic drugs correspond to the type of individual behavioral response."}
{"id": "PMID:26612", "title": "Local graft-versus-host reaction in mice evoked by Peyer's patch and other lymphoid tissue cells tested in a lymphocyte-induced angiogenesis assay.", "content": "The competence of murine Peyer's patch cells to evoke a local GVH reaction was compared with that displayed by lymphoid cells of spleen, lymph nodes, thymus, bone marrow, peritoneal cavity and peripheral blood. The local GVH reaction was assessed in a lymphocyte-induced angiogenesis assay in which an intradermal injection of lymphoid cells results in a new blood vessel formation at the injection site, and the number of vessels corresponds to the number of the immunocompetent cells injected. Peyer's patch cells were capable of mounting a local GVH reaction of intensity comparable to that evoked by the corresponding number of thymus cells or a four times lower number of spleen cells. The highest activity was exhibited by lymph node and peripheral blood cells while bone marrow cells were the least active. A striking increase in angiogenic response was observed after X-irradiation of the recipients with 700R.", "contents": "Local graft-versus-host reaction in mice evoked by Peyer's patch and other lymphoid tissue cells tested in a lymphocyte-induced angiogenesis assay. The competence of murine Peyer's patch cells to evoke a local GVH reaction was compared with that displayed by lymphoid cells of spleen, lymph nodes, thymus, bone marrow, peritoneal cavity and peripheral blood. The local GVH reaction was assessed in a lymphocyte-induced angiogenesis assay in which an intradermal injection of lymphoid cells results in a new blood vessel formation at the injection site, and the number of vessels corresponds to the number of the immunocompetent cells injected. Peyer's patch cells were capable of mounting a local GVH reaction of intensity comparable to that evoked by the corresponding number of thymus cells or a four times lower number of spleen cells. The highest activity was exhibited by lymph node and peripheral blood cells while bone marrow cells were the least active. A striking increase in angiogenic response was observed after X-irradiation of the recipients with 700R."}
{"id": "PMID:26613", "title": "Serum polyphenol oxidase activity (ceruloplasmin) in conventional laboratory animals and man.", "content": "The optimum pH for ceruloplasmin as polyphenol oxidase (EC 1.10.3.2) activity was determined in human serum (pH 5.4) and the serum of conventional laboratory animals--the rat (pH 5.2), mouse (pH 5.2), hamster (pH 5.3), guinea pig (pH 5.4), multimammate mouse (pH 5.2) and rabbit (pH 5.4). Determined at the optimum pH in 0.1M acetate buffer polyphenol oxidase activity fell in the sequence: rat--man--rabbit--mouse--multimammate mouse--hamster--guinea pig. Ceruloplasmin polyphenol oxidase activity was inhibited by 0.1M phosphate buffer in the mouse, rat and multimammate mouse, but not in the other species. It was inhibited by 0.05M citrate and 0.1M phthalate buffer in all the species tested.", "contents": "Serum polyphenol oxidase activity (ceruloplasmin) in conventional laboratory animals and man. The optimum pH for ceruloplasmin as polyphenol oxidase (EC 1.10.3.2) activity was determined in human serum (pH 5.4) and the serum of conventional laboratory animals--the rat (pH 5.2), mouse (pH 5.2), hamster (pH 5.3), guinea pig (pH 5.4), multimammate mouse (pH 5.2) and rabbit (pH 5.4). Determined at the optimum pH in 0.1M acetate buffer polyphenol oxidase activity fell in the sequence: rat--man--rabbit--mouse--multimammate mouse--hamster--guinea pig. Ceruloplasmin polyphenol oxidase activity was inhibited by 0.1M phosphate buffer in the mouse, rat and multimammate mouse, but not in the other species. It was inhibited by 0.05M citrate and 0.1M phthalate buffer in all the species tested."}
{"id": "PMID:26614", "title": "Evaluation of in vitro and in vivo activities of isoantibodies directed against idiotypes and recognition structures for transplantation antigens.", "content": "Anti-idiotype sera were prepared by injection of CBA anti-A/JAX serum with or without adjuvant into CBA mice. These sera were tested in allocluster inhibition and passive enhancement-facilitation. While the anti-idiotype sera inhibited allocluster formation, particularly when prepared with complete Freund's adjuvant, they had virtually no effect on enhancement of Sa I grafted in CBA mice except for a marginal prolongation of graft survival in one out of three experiments. Anti-RS serum was prepared by immunizing (CBA X A)F1 mice with CBA thymus or spleen cells. The sera were tested in local graft-versus-host inhibition and passive enhancement. F1 anti-CBA thymus serum inhibited the local graft-versus-host reaction but had no enhancing effect. F1 anti-CBA spleen serum was virtually ineffective in both tests although a slight tendency to graft-versus-host inhibition was noted. The relative contribution of anti-idiotype and/or anti-RS antibodies to transplantation reactions is discussed.", "contents": "Evaluation of in vitro and in vivo activities of isoantibodies directed against idiotypes and recognition structures for transplantation antigens. Anti-idiotype sera were prepared by injection of CBA anti-A/JAX serum with or without adjuvant into CBA mice. These sera were tested in allocluster inhibition and passive enhancement-facilitation. While the anti-idiotype sera inhibited allocluster formation, particularly when prepared with complete Freund's adjuvant, they had virtually no effect on enhancement of Sa I grafted in CBA mice except for a marginal prolongation of graft survival in one out of three experiments. Anti-RS serum was prepared by immunizing (CBA X A)F1 mice with CBA thymus or spleen cells. The sera were tested in local graft-versus-host inhibition and passive enhancement. F1 anti-CBA thymus serum inhibited the local graft-versus-host reaction but had no enhancing effect. F1 anti-CBA spleen serum was virtually ineffective in both tests although a slight tendency to graft-versus-host inhibition was noted. The relative contribution of anti-idiotype and/or anti-RS antibodies to transplantation reactions is discussed."}
{"id": "PMID:26620", "title": "Interaction of glucocorticoid receptors from lymphoid cell lines with their nuclear acceptor sites.", "content": "Procedures have been developed which provide simple means of determining binding constants of steroid receptors for glucocorticoids in mouse lymphoid cell lines and of characterizing the interaction of the steroid--receptor complex with the nucleus. An average of 70% of the steroid--receptor complexes is found associated with the nuclear fraction in three investigated cell lines, whereas 30% of the steroid--receptor complexes is found in the cytosol fraction. This distribution of the steroid-receptor complex within the cell is independent of whether steroid uptake of the cells is performed at low or at high steroid concentration. Part of the binding of the steroid receptor to the nuclear fraction is sensitive to high ionic strength and to high pH. A larger fraction of the steroid--receptor complex binding to the nuclear fraction is insensitive to high ionic strength and pH when the steroid uptake is performed at low steroid concentrations than when performed at high steroid concentrations. Steroid--receptor complex is released from the nuclear fraction by DNAase treatment but not by RNAase treatment. The possible correlation between the sensitivity to ionic strength and pH and the specificity of the binding is discussed.", "contents": "Interaction of glucocorticoid receptors from lymphoid cell lines with their nuclear acceptor sites. Procedures have been developed which provide simple means of determining binding constants of steroid receptors for glucocorticoids in mouse lymphoid cell lines and of characterizing the interaction of the steroid--receptor complex with the nucleus. An average of 70% of the steroid--receptor complexes is found associated with the nuclear fraction in three investigated cell lines, whereas 30% of the steroid--receptor complexes is found in the cytosol fraction. This distribution of the steroid-receptor complex within the cell is independent of whether steroid uptake of the cells is performed at low or at high steroid concentration. Part of the binding of the steroid receptor to the nuclear fraction is sensitive to high ionic strength and to high pH. A larger fraction of the steroid--receptor complex binding to the nuclear fraction is insensitive to high ionic strength and pH when the steroid uptake is performed at low steroid concentrations than when performed at high steroid concentrations. Steroid--receptor complex is released from the nuclear fraction by DNAase treatment but not by RNAase treatment. The possible correlation between the sensitivity to ionic strength and pH and the specificity of the binding is discussed."}
{"id": "PMID:26626", "title": "Effect of cimetidine on ion fluxes and potential difference across the human stomach.", "content": "The H(2)-receptor antagonist, cimetidine, reduces acid output regardless of the means of stimulation. It is not known in man whether this is due entirely to a reduction in acid secretion or whether increased back diffusion of hydrogen ions is also occurring. We studied fluxes of H(+), Na(+), K(+), and Cl(-) ions after acid instillation into the human stomach in six healthy subjects with and without prior administration of 300 mg cimetidine orally. Potential difference across gastric mucosa was measured continuously throughout each study. Cimetidine caused a significant reduction in hydrogen ion secretion (5.05 mEq per 15 minutes controls versus 2.70 cimetidine, p < 0.05), and consequently a significant reduction in net hydrogen flux into the gastric lumen (2.01 mEq per 15 minutes versus 0.02, p < 0.05). There were no significant differences between sodium ion fluxes in control and cimetidine studies, suggesting that the gastric mucosal barrier remained intact. Cimetidine alone caused a highly significant rise in intragastric pH (to 7) and of potential difference (p < 0.001). Addition of intragastric acid (pH < 1.0) did not reverse the rise in potential difference caused by cimetidine, suggesting that factors other than change in intragastric pH were involved. In conclusion, our studies support the concept that reduction in acid output by cimetidine is due to inhibition of acid secretion, and not to increased permeability to hydrogen ion.", "contents": "Effect of cimetidine on ion fluxes and potential difference across the human stomach. The H(2)-receptor antagonist, cimetidine, reduces acid output regardless of the means of stimulation. It is not known in man whether this is due entirely to a reduction in acid secretion or whether increased back diffusion of hydrogen ions is also occurring. We studied fluxes of H(+), Na(+), K(+), and Cl(-) ions after acid instillation into the human stomach in six healthy subjects with and without prior administration of 300 mg cimetidine orally. Potential difference across gastric mucosa was measured continuously throughout each study. Cimetidine caused a significant reduction in hydrogen ion secretion (5.05 mEq per 15 minutes controls versus 2.70 cimetidine, p < 0.05), and consequently a significant reduction in net hydrogen flux into the gastric lumen (2.01 mEq per 15 minutes versus 0.02, p < 0.05). There were no significant differences between sodium ion fluxes in control and cimetidine studies, suggesting that the gastric mucosal barrier remained intact. Cimetidine alone caused a highly significant rise in intragastric pH (to 7) and of potential difference (p < 0.001). Addition of intragastric acid (pH < 1.0) did not reverse the rise in potential difference caused by cimetidine, suggesting that factors other than change in intragastric pH were involved. In conclusion, our studies support the concept that reduction in acid output by cimetidine is due to inhibition of acid secretion, and not to increased permeability to hydrogen ion."}
{"id": "PMID:26627", "title": "p-Nitrobenzyl p-toluenesulfonyl-L-arginine: a chromogenic substrate for thrombin, plasmin and trypsin.", "content": "p-Nitrobenzyl p-toluenesulfonyl-L-arginine is hydrolyzed by thrombin, plasmin, and trypsin to p-nitrobenzyl alcohol and tosyl-L-arginine. The absorption of p-nitrobenzyl alcohol formed is measured at 271 nm (AmM 8.89). With 0.10 mM of the ester in 0.1 M Tris-HCl at pH 8.4 and 30 degrees C, the hydrolysis catalyzed by thrombin, plasmin, and trypsin is linearly proportional to time up to consumption of 60% of the substrate. Km is 14 micron and Vmax is 0.037 mumol/min/NIH unit for bovine thrombin, Km is 78 micron and Vmax is 0.31 mumol/min/CTA unit/ml for human plasmin, and Km is 12 micron and Vmax is 138 mumol/min/mg protein/ml for bovine trypsin. Samples of bovine and human thrombin ranging in specific clotting activity from 59 to 2,133 NIH units/mg protein showed esterase activities ranging from 0.15 to 0.4 mumol p-nitrobenzyl alcohol formed/10 min/NIH unit. Useful ranges for assay of enzymes were (per milliliter): 0.05-0.2 NIH units (thrombin), 0.005-0.02 CTA units (plasmin), and 0.01-0.04 microgram (trypsin).", "contents": "p-Nitrobenzyl p-toluenesulfonyl-L-arginine: a chromogenic substrate for thrombin, plasmin and trypsin. p-Nitrobenzyl p-toluenesulfonyl-L-arginine is hydrolyzed by thrombin, plasmin, and trypsin to p-nitrobenzyl alcohol and tosyl-L-arginine. The absorption of p-nitrobenzyl alcohol formed is measured at 271 nm (AmM 8.89). With 0.10 mM of the ester in 0.1 M Tris-HCl at pH 8.4 and 30 degrees C, the hydrolysis catalyzed by thrombin, plasmin, and trypsin is linearly proportional to time up to consumption of 60% of the substrate. Km is 14 micron and Vmax is 0.037 mumol/min/NIH unit for bovine thrombin, Km is 78 micron and Vmax is 0.31 mumol/min/CTA unit/ml for human plasmin, and Km is 12 micron and Vmax is 138 mumol/min/mg protein/ml for bovine trypsin. Samples of bovine and human thrombin ranging in specific clotting activity from 59 to 2,133 NIH units/mg protein showed esterase activities ranging from 0.15 to 0.4 mumol p-nitrobenzyl alcohol formed/10 min/NIH unit. Useful ranges for assay of enzymes were (per milliliter): 0.05-0.2 NIH units (thrombin), 0.005-0.02 CTA units (plasmin), and 0.01-0.04 microgram (trypsin)."}
{"id": "PMID:26628", "title": "Chromogenic substrate assay of plasma prekallikrein. With a note on its site of biosynthesis.", "content": "A method for assaying plasma prekallikrein has been developed applying the chromogenic substrate Chromozym PK. Different variables have been investigated, and the final assay system was found to give a reproducible and reliable assay procedure. A normal value of 99.0 +/- 18% was found, the coefficient of variation being 7.9. Studies on material from patients with various liver diseases indicated that the main site of prekallikrein biosynthesis is the liver.", "contents": "Chromogenic substrate assay of plasma prekallikrein. With a note on its site of biosynthesis. A method for assaying plasma prekallikrein has been developed applying the chromogenic substrate Chromozym PK. Different variables have been investigated, and the final assay system was found to give a reproducible and reliable assay procedure. A normal value of 99.0 +/- 18% was found, the coefficient of variation being 7.9. Studies on material from patients with various liver diseases indicated that the main site of prekallikrein biosynthesis is the liver."}
{"id": "PMID:26629", "title": "Methods for determination of prekallikrein in plasma, glandular kallikrein and urokinase.", "content": "New chromogenic tripeptide substrates have been used for the determination of kallikreins and urokinase. The conditions have been optimized. It is possible to determine prekallikrein in plasma after activation with Cephotest. No significant loss in activity caused by plasma kallikrein inhibitors is observed at the dilutions used.", "contents": "Methods for determination of prekallikrein in plasma, glandular kallikrein and urokinase. New chromogenic tripeptide substrates have been used for the determination of kallikreins and urokinase. The conditions have been optimized. It is possible to determine prekallikrein in plasma after activation with Cephotest. No significant loss in activity caused by plasma kallikrein inhibitors is observed at the dilutions used."}
{"id": "PMID:26631", "title": "[Regional myocardial blood supply in coronary disease].", "content": "1. Value and limitations of the precordial Xenon-clearance technique are analyzed. The results of this technique are compared to the scintigraphic display of the initial Xenon distribution and to microsphere scintigraphy (Engel et al. 1976a). 2. The effects of coronary obstructions and of segmental LV dysfunction on regional myocardial blood flow are analyzed (Engel et al. 1977). Independent of coronary obstructions, a clear reduction of regional myocardial blood flow in areas of hypokinesis and akinesis was observed. Thus in coronary disease a decrease of regional myocardial blood flow may represent either a cause or a result of abnormal segmental wall motion. 3. The effects of nitroglycerin, beta-blockade (Atenolol), calcium-antagonists (Nifedipine) and coronary dilatation (Dipyridamole) on regional myocardial blood flow were investigated (Engel et al. 1976b). Regional flow at rest decreased after nitroglycerin and beta-blockade, increased mildly after Nifedipine and markedly after Dipyridamole.", "contents": "[Regional myocardial blood supply in coronary disease]. 1. Value and limitations of the precordial Xenon-clearance technique are analyzed. The results of this technique are compared to the scintigraphic display of the initial Xenon distribution and to microsphere scintigraphy (Engel et al. 1976a). 2. The effects of coronary obstructions and of segmental LV dysfunction on regional myocardial blood flow are analyzed (Engel et al. 1977). Independent of coronary obstructions, a clear reduction of regional myocardial blood flow in areas of hypokinesis and akinesis was observed. Thus in coronary disease a decrease of regional myocardial blood flow may represent either a cause or a result of abnormal segmental wall motion. 3. The effects of nitroglycerin, beta-blockade (Atenolol), calcium-antagonists (Nifedipine) and coronary dilatation (Dipyridamole) on regional myocardial blood flow were investigated (Engel et al. 1976b). Regional flow at rest decreased after nitroglycerin and beta-blockade, increased mildly after Nifedipine and markedly after Dipyridamole."}
{"id": "PMID:26632", "title": "[On the acute toxicity of labetalol (AH-5158), a combined alpha-and-beta-adrenoceptor-blocking agent (author's transl)].", "content": "Acute toxicity studies in labetalol were performed using mice, rats and rabbits, An oral administration of labetalol produced an increase in salivary secretion due to local irritation. Death followed convulsions by large doses of labetalol. Pathological examinations suggested that the cause of death by labetalol was circulatory disturbances due to the damage of heart muscles and a subsequent respiratory paralysis. Parenteral LD50 showed almost the same values among mice (50 mg/kg iv, 117 mg/kg ip), rats (66 mg/kg iv, 115 mg/kg ip) and rabbits (43 mg/kg iv). However, species difference was seen in oral LD50 values which were enormously large as compared with iv LD50 values.", "contents": "[On the acute toxicity of labetalol (AH-5158), a combined alpha-and-beta-adrenoceptor-blocking agent (author's transl)]. Acute toxicity studies in labetalol were performed using mice, rats and rabbits, An oral administration of labetalol produced an increase in salivary secretion due to local irritation. Death followed convulsions by large doses of labetalol. Pathological examinations suggested that the cause of death by labetalol was circulatory disturbances due to the damage of heart muscles and a subsequent respiratory paralysis. Parenteral LD50 showed almost the same values among mice (50 mg/kg iv, 117 mg/kg ip), rats (66 mg/kg iv, 115 mg/kg ip) and rabbits (43 mg/kg iv). However, species difference was seen in oral LD50 values which were enormously large as compared with iv LD50 values."}
{"id": "PMID:26633", "title": "Gastric lesions in familial adenomatosis coli: their incidence and histologic analysis.", "content": "In order to detect accompanying gastric lesions, we examined 22 patients with familial adenomatosis of the colon belonging to 14 families. Various gastric lesions were confirmed in 15 patients (68.2 per cent) belonging to 13 families. The lesions were found histologically to be adenoma in nine cases, fundic gland polyposis in six, carcinoma in three, and microcarcinoid in two. Fundic gland polyposis consisting of simple hyperplasia of the fundic glands seems to be the gastric lesion specific to familial adenomatosis of the colon and rectum. Familial adenomatosis coli not only affects the colon and rectum, but is also capable of inducing tumorigenicity in other organs. The stomach is one of the organs in which extracolonic lesions occur.", "contents": "Gastric lesions in familial adenomatosis coli: their incidence and histologic analysis. In order to detect accompanying gastric lesions, we examined 22 patients with familial adenomatosis of the colon belonging to 14 families. Various gastric lesions were confirmed in 15 patients (68.2 per cent) belonging to 13 families. The lesions were found histologically to be adenoma in nine cases, fundic gland polyposis in six, carcinoma in three, and microcarcinoid in two. Fundic gland polyposis consisting of simple hyperplasia of the fundic glands seems to be the gastric lesion specific to familial adenomatosis of the colon and rectum. Familial adenomatosis coli not only affects the colon and rectum, but is also capable of inducing tumorigenicity in other organs. The stomach is one of the organs in which extracolonic lesions occur."}
{"id": "PMID:26634", "title": "Morphologic aspects of bone marrow transplantation in patients with aplastic anemia.", "content": "Pre- and post-transplant bone marrow samples from 20 patients with aplastic anemia were studied. Morphologic evidence of marrow reconstitution was noted in 18 patients one to three weeks following transplantation. In most instances the engrafted marrow elements in early weeks appeared as small clusters of erythroid or myeloid precursors. Bone marrow biopsy or clot sections obtained four to eight weeks after transplantation were more cellular with larger clusters of hematopoietic cells, which were most often composed of mixed cellular elements, including megakaryocytes. Two patients with morphologic evidence of engraftment died shortly after transplantation and were excluded from further analysis. In four of the remaining 16 patients grafts were \"rejected\" three to eight weeks after transplant. A fifth patient who received a marrow graft from his identical twin showed a transient increase in marrow cellularity without clinical improvement. However, the second marrow transplantation in this patient using the same donor after conditioning with cyclophosphamide resulted in moderate clinical improvement. In four of the five patients developing graft \"rejection\" or failure there was an increase in marrow mast cells in pre- and post-transplant marrow samples. In contrast, only two of 11 patients with successful engraftment had an increase in mast cells. Although the pathophysiologic role of mast cells in marrow transplantation is unclear, the present study suggests a possible inverse correlation between the numbers of marrow mast cells and the likelihood of successful engraftment. Bone marrow samples in patients with graft versus host disease displayed a slight increase in the number of eosinophils, lymphocytes, and plasma cells.", "contents": "Morphologic aspects of bone marrow transplantation in patients with aplastic anemia. Pre- and post-transplant bone marrow samples from 20 patients with aplastic anemia were studied. Morphologic evidence of marrow reconstitution was noted in 18 patients one to three weeks following transplantation. In most instances the engrafted marrow elements in early weeks appeared as small clusters of erythroid or myeloid precursors. Bone marrow biopsy or clot sections obtained four to eight weeks after transplantation were more cellular with larger clusters of hematopoietic cells, which were most often composed of mixed cellular elements, including megakaryocytes. Two patients with morphologic evidence of engraftment died shortly after transplantation and were excluded from further analysis. In four of the remaining 16 patients grafts were \"rejected\" three to eight weeks after transplant. A fifth patient who received a marrow graft from his identical twin showed a transient increase in marrow cellularity without clinical improvement. However, the second marrow transplantation in this patient using the same donor after conditioning with cyclophosphamide resulted in moderate clinical improvement. In four of the five patients developing graft \"rejection\" or failure there was an increase in marrow mast cells in pre- and post-transplant marrow samples. In contrast, only two of 11 patients with successful engraftment had an increase in mast cells. Although the pathophysiologic role of mast cells in marrow transplantation is unclear, the present study suggests a possible inverse correlation between the numbers of marrow mast cells and the likelihood of successful engraftment. Bone marrow samples in patients with graft versus host disease displayed a slight increase in the number of eosinophils, lymphocytes, and plasma cells."}
{"id": "PMID:26636", "title": "Mice bearing the ob/ob mutation have impaired immunity.", "content": "The obese mutant mouse C57BL/6J ob/ob showed impaired ability to reject skin grafts or react to a contact-sensitising agent in comparison with littermate controls (either +/ob or +/+). Ability of spleen cells from mice bearing the ob/ob mutation to produce a graft-versus-host reaction in C57BL/6J X DBA/2J F1 hybrid mice was not impaired.", "contents": "Mice bearing the ob/ob mutation have impaired immunity. The obese mutant mouse C57BL/6J ob/ob showed impaired ability to reject skin grafts or react to a contact-sensitising agent in comparison with littermate controls (either +/ob or +/+). Ability of spleen cells from mice bearing the ob/ob mutation to produce a graft-versus-host reaction in C57BL/6J X DBA/2J F1 hybrid mice was not impaired."}
{"id": "PMID:26637", "title": "Interaction of cholera toxin and toxin derivatives with lymphocytes. III. Modulating effects in vivo by cholera toxin on the graft-versus-host reactivity of lymphoid cells: suggested inhibition of suppressor cells.", "content": "The influence of cholera toxin (CT), and thus probably of cyclic AMP, on the capacity of parental lymphoid cells to elicit a graft-versus-host reaction (GVHR) was studied. Toxin-treated DBA/1 mice were used as cell donors and untreated DBA/1xC57B1/6 F1 hybrid mice as recipients, and the GVHR reactivity of the transferred cells was estimated by their ability to induce spleen enlargement or stimulation of antibody formation ('allogenic effect') in the recipients. Spleen cells from donors intravenously injected with 1 microgram CT 1-3 days earlier, gave a significantly stronger GVHR than did spleen cells of untreated mice. Choleragenoid, a toxin analog devoid of the toxin's ability to activate plasma membrane adenylate cyclase even though it binds efficiently to cells, had no effect on the GVHR-inducing capacity of the spleen cells. The enhanced GVHR by spleen cells from toxin-treated DBA/1 animals was reduced to the normal level when the donor cells were transferred along with lymphoid cells from untreated animals of the same strain. Spleen was the most powerful source of the suppressive influence. No evidence for a redistribution of suppressor cells following administration of CT was found. Spleen cells from mice syngeneic with the recipients had no suppressive effect. The results suggest that parenterally administered CT, directly or indirectly, can inhibit a cell population in spleen which normally exerts an antigen-specific suppressive regulatory influence on the development of GVHR.", "contents": "Interaction of cholera toxin and toxin derivatives with lymphocytes. III. Modulating effects in vivo by cholera toxin on the graft-versus-host reactivity of lymphoid cells: suggested inhibition of suppressor cells. The influence of cholera toxin (CT), and thus probably of cyclic AMP, on the capacity of parental lymphoid cells to elicit a graft-versus-host reaction (GVHR) was studied. Toxin-treated DBA/1 mice were used as cell donors and untreated DBA/1xC57B1/6 F1 hybrid mice as recipients, and the GVHR reactivity of the transferred cells was estimated by their ability to induce spleen enlargement or stimulation of antibody formation ('allogenic effect') in the recipients. Spleen cells from donors intravenously injected with 1 microgram CT 1-3 days earlier, gave a significantly stronger GVHR than did spleen cells of untreated mice. Choleragenoid, a toxin analog devoid of the toxin's ability to activate plasma membrane adenylate cyclase even though it binds efficiently to cells, had no effect on the GVHR-inducing capacity of the spleen cells. The enhanced GVHR by spleen cells from toxin-treated DBA/1 animals was reduced to the normal level when the donor cells were transferred along with lymphoid cells from untreated animals of the same strain. Spleen was the most powerful source of the suppressive influence. No evidence for a redistribution of suppressor cells following administration of CT was found. Spleen cells from mice syngeneic with the recipients had no suppressive effect. The results suggest that parenterally administered CT, directly or indirectly, can inhibit a cell population in spleen which normally exerts an antigen-specific suppressive regulatory influence on the development of GVHR."}
{"id": "PMID:26640", "title": "[Acute mucocutaneous lymph node syndrome (Kawasaki-syndrome) with fatal periarteritis nodosa of the coronary arteries. Another case from Europe].", "content": "Case report of a 1 8/12-year-old boy suffering from an acute febrile disease with phlegmonous cervical lymphadenopathy, skin rash and other septic symptoms. Bacterial cultures were sterile, and antibiotics had no effect, whereas prednisone made an immediate improvement. On the 23rd day of illness the patient died unexpectedly. Autopsy revealed a ruptured coronary aneurysm due to periarteritis nodosa. This curious disease of yet unknown cause is quite frequent in Japan, but very rare in Europe.", "contents": "[Acute mucocutaneous lymph node syndrome (Kawasaki-syndrome) with fatal periarteritis nodosa of the coronary arteries. Another case from Europe]. Case report of a 1 8/12-year-old boy suffering from an acute febrile disease with phlegmonous cervical lymphadenopathy, skin rash and other septic symptoms. Bacterial cultures were sterile, and antibiotics had no effect, whereas prednisone made an immediate improvement. On the 23rd day of illness the patient died unexpectedly. Autopsy revealed a ruptured coronary aneurysm due to periarteritis nodosa. This curious disease of yet unknown cause is quite frequent in Japan, but very rare in Europe."}
{"id": "PMID:26641", "title": "Light and electron microscopic study of adenosine triphosphatase activity of anuran tadpole musculature.", "content": "The histochemical activities of succinic dehydrogenase (SDH) and Ca++-activated ATPase (pHs 7.4 and 9.4) were studied in the larval tail musculature of Rana japonica, Rana catesbeiana and Rana ornativentris. The ATPase reaction product was detected by both light and electron microscopy. 'Red' and 'white' muscle fibres, as distinguished by SDH, showed high and low Ca++-ATPase reaction, respectively, at pHs 7.4, 9.4 and following preincubation in cold K2-EDTA solution. The ultrastructural investigation of Ca++-ATPase reaction at pH 7.4 by the Ca++-citrophosphate technique demonstrated electron-dense reaction product in association with A, I and 'Z' bands, intermyofibrillar (SR) compartment and the mitochondrial inner chamber. However, Pb++ precipitation technique demonstrated Mg++-activated myosin ATPase activity at pH 9.2 ultrastructurally. The present histochemical data suggest that the anuran larval tail 'red' muscle fibres are possible 'slow,' and emphasize a possible lack of correlation between the speed of contraction with their ATPase activity. Moreover, 'red' muscle fibres of the anuran tai- musculature are not equivalent to 'Type I' fibres of higher chordates.", "contents": "Light and electron microscopic study of adenosine triphosphatase activity of anuran tadpole musculature. The histochemical activities of succinic dehydrogenase (SDH) and Ca++-activated ATPase (pHs 7.4 and 9.4) were studied in the larval tail musculature of Rana japonica, Rana catesbeiana and Rana ornativentris. The ATPase reaction product was detected by both light and electron microscopy. 'Red' and 'white' muscle fibres, as distinguished by SDH, showed high and low Ca++-ATPase reaction, respectively, at pHs 7.4, 9.4 and following preincubation in cold K2-EDTA solution. The ultrastructural investigation of Ca++-ATPase reaction at pH 7.4 by the Ca++-citrophosphate technique demonstrated electron-dense reaction product in association with A, I and 'Z' bands, intermyofibrillar (SR) compartment and the mitochondrial inner chamber. However, Pb++ precipitation technique demonstrated Mg++-activated myosin ATPase activity at pH 9.2 ultrastructurally. The present histochemical data suggest that the anuran larval tail 'red' muscle fibres are possible 'slow,' and emphasize a possible lack of correlation between the speed of contraction with their ATPase activity. Moreover, 'red' muscle fibres of the anuran tai- musculature are not equivalent to 'Type I' fibres of higher chordates."}
{"id": "PMID:26650", "title": "Microbial metabolism of anthracycline antibiotics daunomycin and adriamycin.", "content": "It has been shown that the antitumor antibiotics daunomycin (1) and adriamycin (4) are metabolized by microorganisms in a fashion similar to their metabolism by mammalian cells. Both the fungus Mucor spinosus and its cell-free extracts reduce the 13-keto group of daunomycin to give daunomycinol (2) by a TPNH-dependent process. Cell-free extracts of Streptomyces steffisburgensis convert adriamycin and daunomycinol to their 7-deoxyaglycones (5) and (3) by DPNH-linked reductive glycosidic cleavage. Cell-free extracts of the latter organism convert 7-deoxyadriamycinone (5) to 7-deoxyadriamycinol aglycone (6) by TPNH-linked 13-keto reduction.", "contents": "Microbial metabolism of anthracycline antibiotics daunomycin and adriamycin. It has been shown that the antitumor antibiotics daunomycin (1) and adriamycin (4) are metabolized by microorganisms in a fashion similar to their metabolism by mammalian cells. Both the fungus Mucor spinosus and its cell-free extracts reduce the 13-keto group of daunomycin to give daunomycinol (2) by a TPNH-dependent process. Cell-free extracts of Streptomyces steffisburgensis convert adriamycin and daunomycinol to their 7-deoxyaglycones (5) and (3) by DPNH-linked reductive glycosidic cleavage. Cell-free extracts of the latter organism convert 7-deoxyadriamycinone (5) to 7-deoxyadriamycinol aglycone (6) by TPNH-linked 13-keto reduction."}
{"id": "PMID:26651", "title": "Semiautomated turbidimetric microbiological assay for cefazaflur.", "content": "A quantitative semi-automated turbidimetric bioassay for cefazaflur, using Streptococcus faecium as the indicator, is described. Assays were run at pH 6.5 approximately 7 for 3.75 hours at 37 degrees C using 2 approximately 12 microgram cefazaflur per ml assay broth for standards. The dose response line was plotted point to point using the natural log of the absorbance vs natural log of the concentration. This assay is both accurate and precise and is more rapid than traditional plate assays for antibiotics.", "contents": "Semiautomated turbidimetric microbiological assay for cefazaflur. A quantitative semi-automated turbidimetric bioassay for cefazaflur, using Streptococcus faecium as the indicator, is described. Assays were run at pH 6.5 approximately 7 for 3.75 hours at 37 degrees C using 2 approximately 12 microgram cefazaflur per ml assay broth for standards. The dose response line was plotted point to point using the natural log of the absorbance vs natural log of the concentration. This assay is both accurate and precise and is more rapid than traditional plate assays for antibiotics."}
{"id": "PMID:26655", "title": "Salmonella typhimurium peptidase active on carnosine.", "content": "Wild-type Salmonella typhimurium can use carnosine (beta-alanyl-L-histidine) as a source of histidine, but carnosine utilization is blocked in particular mutants defective in the constitutive enzyme peptidase D, the product of the pepD gene. Biochemical evidence for assigning carnosinase activity to peptidase D (a broad-specificity dipeptidase) includes: (i) coelution of carnosinase and dipeptidase activity from diethylaminoethyl-cellulose and Bio-Gel P-300 columns; (ii) coelectrophoresis of carnosinase and dipeptidase on polyacrylamide gels; and (iii) inactivation of carnosinase and dipeptidase activities at identical rates at both 4 and 42 degrees C. Genetic evidence indicates that mutations leading to loss of carnosinase activity map at pepD. Several independent pepD mutants have been isolated by different selection procedures, and the patterns of peptide utilization of strains carrying various pepD alleles have been studied. Many pepD mutations lead to the production of partially active peptidase D enzymes with substrate specificities that differ strikingly from those of the wild-type enzyme. The growth yields of carnosinase-deficient strains growing in Difco nutrient broth indicate that carnosine is the major utilizable source of histidine in this medium.", "contents": "Salmonella typhimurium peptidase active on carnosine. Wild-type Salmonella typhimurium can use carnosine (beta-alanyl-L-histidine) as a source of histidine, but carnosine utilization is blocked in particular mutants defective in the constitutive enzyme peptidase D, the product of the pepD gene. Biochemical evidence for assigning carnosinase activity to peptidase D (a broad-specificity dipeptidase) includes: (i) coelution of carnosinase and dipeptidase activity from diethylaminoethyl-cellulose and Bio-Gel P-300 columns; (ii) coelectrophoresis of carnosinase and dipeptidase on polyacrylamide gels; and (iii) inactivation of carnosinase and dipeptidase activities at identical rates at both 4 and 42 degrees C. Genetic evidence indicates that mutations leading to loss of carnosinase activity map at pepD. Several independent pepD mutants have been isolated by different selection procedures, and the patterns of peptide utilization of strains carrying various pepD alleles have been studied. Many pepD mutations lead to the production of partially active peptidase D enzymes with substrate specificities that differ strikingly from those of the wild-type enzyme. The growth yields of carnosinase-deficient strains growing in Difco nutrient broth indicate that carnosine is the major utilizable source of histidine in this medium."}
{"id": "PMID:26656", "title": "Aspartokinase of Streptococcus mutans: purification, properties, and regulation.", "content": "Aspartokinase from Streptococcus mutans BHT was purified to homogeneity and characterized. The molecular weight of the native enzyme was estimated to be 242,000 by gel filtration. Cross-linking of aspartokinase with dimethyl suberimidate and polyacrylamide gel electrophoresis of the amidinated enzyme in the presence of sodium dodecyl sulfate showed the enzyme to be composed of six identical subunits with a molecular wieght of 40,000. The optimal pH range for enzyme activity was 6.5 to 8.5. The apparent Michaelis-Menten constants for aspartate and ATP were 5.5 and 2.2 mM, respectively. The enzyme was stable within the temperature range of 10 to 35 degrees C. Aspartokinase was not feedback inhibited by individual amino acids, but was concertedly inhibited by L-lysine and L-threonine (93.5% inhibition at 10 mM each). The inhibition was noncompetitive with respect to aspartate (Ki = 10 mM) and mixed with respect to ATP. L-Threonine methyl ester and L-threonine amide were able to substitute for L-threonine in feedback inhibition, but the requirement for L-lysine uas strict. The feedback inhibitor pair protected the enzyme against heat denaturation. Aspartokinase synthesis was repressed by L-threonine; this repression was enhanced by L-lysine, but was slightly attenuated by L-methionine.", "contents": "Aspartokinase of Streptococcus mutans: purification, properties, and regulation. Aspartokinase from Streptococcus mutans BHT was purified to homogeneity and characterized. The molecular weight of the native enzyme was estimated to be 242,000 by gel filtration. Cross-linking of aspartokinase with dimethyl suberimidate and polyacrylamide gel electrophoresis of the amidinated enzyme in the presence of sodium dodecyl sulfate showed the enzyme to be composed of six identical subunits with a molecular wieght of 40,000. The optimal pH range for enzyme activity was 6.5 to 8.5. The apparent Michaelis-Menten constants for aspartate and ATP were 5.5 and 2.2 mM, respectively. The enzyme was stable within the temperature range of 10 to 35 degrees C. Aspartokinase was not feedback inhibited by individual amino acids, but was concertedly inhibited by L-lysine and L-threonine (93.5% inhibition at 10 mM each). The inhibition was noncompetitive with respect to aspartate (Ki = 10 mM) and mixed with respect to ATP. L-Threonine methyl ester and L-threonine amide were able to substitute for L-threonine in feedback inhibition, but the requirement for L-lysine uas strict. The feedback inhibitor pair protected the enzyme against heat denaturation. Aspartokinase synthesis was repressed by L-threonine; this repression was enhanced by L-lysine, but was slightly attenuated by L-methionine."}
{"id": "PMID:26657", "title": "Carboxypeptidase displaying differential velocity in hydrolysis of methotrexate, 5-methyltetrahydrofolic acid, and leucovorin.", "content": "An enzyme that catalyzes the hydrolysis of folic acid and the antifolate methotrexate nearly 20 times more rapidly than the hydrolysis of 5-methyltetrahydrofolate was extraced from a gram-negative bacterium tentatively identified as a Flavobacterium sp. The enzyme was purified 500-fold and found to have a molecular weight of about 53,000. Apparently a metallo-enzyme, it is inhibited by citrate and ethylenediaminetetraacetic acid (EDTA). Ca2+, Co2+, Mg2+, and Zn2+ reverse inhibition by EDTA, whereas Ca2+ and Zn2+ are weak activators in the absence of EDTA. The enzymatic reaction releases the carboxy-terminal glutamyl moiety of derivatives of pteroyl-mono-L-glutamic acid. Substituents on N5 of the pteridine ring decrease the velocity of hydrolysis. Some non-specificity for the terminal amino acid is expressed. The strikingly different rates of hydrolysis of methotrexate and 5-methyltetrahydrofolate have stimulated interest in this enzyme for its potential clinical value in improving the therapeutic index of methotrexate.", "contents": "Carboxypeptidase displaying differential velocity in hydrolysis of methotrexate, 5-methyltetrahydrofolic acid, and leucovorin. An enzyme that catalyzes the hydrolysis of folic acid and the antifolate methotrexate nearly 20 times more rapidly than the hydrolysis of 5-methyltetrahydrofolate was extraced from a gram-negative bacterium tentatively identified as a Flavobacterium sp. The enzyme was purified 500-fold and found to have a molecular weight of about 53,000. Apparently a metallo-enzyme, it is inhibited by citrate and ethylenediaminetetraacetic acid (EDTA). Ca2+, Co2+, Mg2+, and Zn2+ reverse inhibition by EDTA, whereas Ca2+ and Zn2+ are weak activators in the absence of EDTA. The enzymatic reaction releases the carboxy-terminal glutamyl moiety of derivatives of pteroyl-mono-L-glutamic acid. Substituents on N5 of the pteridine ring decrease the velocity of hydrolysis. Some non-specificity for the terminal amino acid is expressed. The strikingly different rates of hydrolysis of methotrexate and 5-methyltetrahydrofolate have stimulated interest in this enzyme for its potential clinical value in improving the therapeutic index of methotrexate."}
{"id": "PMID:26658", "title": "Glutamate-induced uptake of proline by Streptomyces antibioticus.", "content": "Streptomyces antibioticus possesses an energy-dependent, carrier mediated transport system for the uptake of L-glutamate and L-proline. Amino acid transport was found to have a temperature optimum of 35 degrees C and a pH optimum from 7.0 to 8.0 for glutamate and 6.5 to 7.5 for proline uptake. Uptake did not depend upon Mg2+, Ca2+, Zn2+, Na+, or Fe2+ ions. Reversible p-hydroxymercuribenzoate inhibition of uptake indicated the involvement of an active sulfhydryl group. L-Glutamate uptake was mediated by a glutamate-inducible, nonspecific transport system, which was extremely stable and was not subject to substrate inhibition by L-proline. On the other hand, L-proline transport was mediated by at least two systems. The L-glutamate-inducible nonspecific system can account for uptake of proline by the mycelium grown in glutamate. In addition, a proline-specific, constitutive transport system was found to be present in the mycelium grown in organic and inorganic nitrogen sources other than L-glutamate. Shift experiments revealed that proline transport is not as stable as glutamate transport when the glutamate-inducible nonspecific system is utilized.", "contents": "Glutamate-induced uptake of proline by Streptomyces antibioticus. Streptomyces antibioticus possesses an energy-dependent, carrier mediated transport system for the uptake of L-glutamate and L-proline. Amino acid transport was found to have a temperature optimum of 35 degrees C and a pH optimum from 7.0 to 8.0 for glutamate and 6.5 to 7.5 for proline uptake. Uptake did not depend upon Mg2+, Ca2+, Zn2+, Na+, or Fe2+ ions. Reversible p-hydroxymercuribenzoate inhibition of uptake indicated the involvement of an active sulfhydryl group. L-Glutamate uptake was mediated by a glutamate-inducible, nonspecific transport system, which was extremely stable and was not subject to substrate inhibition by L-proline. On the other hand, L-proline transport was mediated by at least two systems. The L-glutamate-inducible nonspecific system can account for uptake of proline by the mycelium grown in glutamate. In addition, a proline-specific, constitutive transport system was found to be present in the mycelium grown in organic and inorganic nitrogen sources other than L-glutamate. Shift experiments revealed that proline transport is not as stable as glutamate transport when the glutamate-inducible nonspecific system is utilized."}
{"id": "PMID:26659", "title": "Glutamine synthetase of Klebsiella aerogenes: properties of glnD mutants lacking uridylyltransferase.", "content": "The glnD mutation of Klebsiella aerogenes is cotransducible by phage P1 with pan (requirement for pantothenate) and leads to a loss of uridylytransferase and uridylyl-removing enzyme, components of the glutamine synthetase adenylylation system. This defect results in an inability to deadenylylate glutamine synthetase rapidly and in a requirement for glutamine for normal growth. Suppression of the glnD mutation are located at the glutamine synthetase structural gene glnA.", "contents": "Glutamine synthetase of Klebsiella aerogenes: properties of glnD mutants lacking uridylyltransferase. The glnD mutation of Klebsiella aerogenes is cotransducible by phage P1 with pan (requirement for pantothenate) and leads to a loss of uridylytransferase and uridylyl-removing enzyme, components of the glutamine synthetase adenylylation system. This defect results in an inability to deadenylylate glutamine synthetase rapidly and in a requirement for glutamine for normal growth. Suppression of the glnD mutation are located at the glutamine synthetase structural gene glnA."}
{"id": "PMID:26660", "title": "Regulation of glutamine synthetase formation in Escherichia coli: characterization of mutants lacking the uridylyltransferase.", "content": "A lambda phage (lambdaNK55) carrying the translocatable element Tn10, conferring tetracycline resistance (Tetr), has been utilized to isolate glutamine auxotrophs of Escherichia coli K-12. Such strains lack uridylyltransferase as a result of an insertion of the TN10 element in the glnD gene. The glnD::Tn10 insertion has been mapped at min 4 on the E. coli chromosome and 98% contransducible by phage P1 with dapD. A lambda transducing phage carrying the glnD gene has been identified. A glnD::Tn10 strain synthesizes highly adenylylated glutamine synthetase under all conditions of growth and fails to accumulate high levels of glutamine synthetase in response to nitrogen limitation. However, this strain, under nitrogen-limiting conditions, allows synthesis of 10 to 20 milliunits of biosynthetically active glutamine synthetase per mg of protein, which is sufficient to allow slow growth in the absence of glutamine. The GlnD phenotype in E. coli can be suppressed by the presence of mutations which increase the quantity of biosynthetically active glutamine synthetase.", "contents": "Regulation of glutamine synthetase formation in Escherichia coli: characterization of mutants lacking the uridylyltransferase. A lambda phage (lambdaNK55) carrying the translocatable element Tn10, conferring tetracycline resistance (Tetr), has been utilized to isolate glutamine auxotrophs of Escherichia coli K-12. Such strains lack uridylyltransferase as a result of an insertion of the TN10 element in the glnD gene. The glnD::Tn10 insertion has been mapped at min 4 on the E. coli chromosome and 98% contransducible by phage P1 with dapD. A lambda transducing phage carrying the glnD gene has been identified. A glnD::Tn10 strain synthesizes highly adenylylated glutamine synthetase under all conditions of growth and fails to accumulate high levels of glutamine synthetase in response to nitrogen limitation. However, this strain, under nitrogen-limiting conditions, allows synthesis of 10 to 20 milliunits of biosynthetically active glutamine synthetase per mg of protein, which is sufficient to allow slow growth in the absence of glutamine. The GlnD phenotype in E. coli can be suppressed by the presence of mutations which increase the quantity of biosynthetically active glutamine synthetase."}
{"id": "PMID:26661", "title": "Purification and properties of the inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase from Chlorella sorokiniana.", "content": "The nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH) of Chlorella sorokiniana was purified 260-fold to electrophoretic homogeneity in six steps. Depending on the techniques used, the native enzyme appeared to have a molecular weight of 290,000 or 410,000 and to be composed of five to seven identical subunits with a molecular weight of 58,000. The amino acid composition of this enzyme was shown to differ considerably from that of the NAD-GDH in this organism. The NH2-terminal amino acid was unavailable to dansylation. All six cysteines in the native enzyme were in the free sulfhydryl form. The pH optima for the aminating and deaminating reactions were 7.2 and 9.2, respectively. The Km values for NH4+, alpha-ketoglutarate, NADPH, L-glutamate, and NADP+ were 68, 12, 0.13, and 0.038 mM, respectively. At low substrate concentrations, no cooperativity was seen; however, severe inhibition of enzyme activity was observed at high alpha-ketoglutarate concentrations. Nucleotides did not affect enzyme activity. Antiserum produced in rabbits to the subunits of the enzyme yielded a single precipitin band with the purified enzyme in Ouchterlony double-diffusion analysis. Immunoelectrophoresis was used to confirm the purity of the enzyme and also to quantify the amount of enzyme antigen. These studies indicate that the NADPH-GDH and NAD-GDH isozymes are distinct molecular species in this organism.", "contents": "Purification and properties of the inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase from Chlorella sorokiniana. The nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH) of Chlorella sorokiniana was purified 260-fold to electrophoretic homogeneity in six steps. Depending on the techniques used, the native enzyme appeared to have a molecular weight of 290,000 or 410,000 and to be composed of five to seven identical subunits with a molecular weight of 58,000. The amino acid composition of this enzyme was shown to differ considerably from that of the NAD-GDH in this organism. The NH2-terminal amino acid was unavailable to dansylation. All six cysteines in the native enzyme were in the free sulfhydryl form. The pH optima for the aminating and deaminating reactions were 7.2 and 9.2, respectively. The Km values for NH4+, alpha-ketoglutarate, NADPH, L-glutamate, and NADP+ were 68, 12, 0.13, and 0.038 mM, respectively. At low substrate concentrations, no cooperativity was seen; however, severe inhibition of enzyme activity was observed at high alpha-ketoglutarate concentrations. Nucleotides did not affect enzyme activity. Antiserum produced in rabbits to the subunits of the enzyme yielded a single precipitin band with the purified enzyme in Ouchterlony double-diffusion analysis. Immunoelectrophoresis was used to confirm the purity of the enzyme and also to quantify the amount of enzyme antigen. These studies indicate that the NADPH-GDH and NAD-GDH isozymes are distinct molecular species in this organism."}
{"id": "PMID:26662", "title": "Regulation of initial rate of induction of nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase during the cell cycle of synchronous Chlorella.", "content": "When synchronous cells of the eucaryotic microorganism Chlorella sorokiniana growing in nitrate medium were challenged to synthesize an ammonium-inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH) at frequent intervals during the cell cycle the initial rate of induction (i.e., enzyme potential) of this enzyme increased in an approximately linear manner until the period of DNA replication (i.e., S phase). During the S phase, NADP-GDH potential exhibited a positive rate change proportional to the step increase in DNA level. The timing of this rate change was insensitive to large changes in cellular growth rate. This rate change could be blocked within the first cell cycle by specific inhibition of DNA replication with 2'-deoxyadenosine. The approximately linear increase in NADP-GDH potential and also of total cellular protein observed before and after the S phase is proposed to be a result of the increasing photosynthetic capacity of the cell during the cell cycle.", "contents": "Regulation of initial rate of induction of nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase during the cell cycle of synchronous Chlorella. When synchronous cells of the eucaryotic microorganism Chlorella sorokiniana growing in nitrate medium were challenged to synthesize an ammonium-inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH) at frequent intervals during the cell cycle the initial rate of induction (i.e., enzyme potential) of this enzyme increased in an approximately linear manner until the period of DNA replication (i.e., S phase). During the S phase, NADP-GDH potential exhibited a positive rate change proportional to the step increase in DNA level. The timing of this rate change was insensitive to large changes in cellular growth rate. This rate change could be blocked within the first cell cycle by specific inhibition of DNA replication with 2'-deoxyadenosine. The approximately linear increase in NADP-GDH potential and also of total cellular protein observed before and after the S phase is proposed to be a result of the increasing photosynthetic capacity of the cell during the cell cycle."}
{"id": "PMID:26663", "title": "Mutations that alter the covalent modification of glutamine synthetase in Salmonella typhimurium.", "content": "glnD and glnE mutant strains of Salmonella typhimurium lack three of the four activities required for reversible covalent modification of glutamine synthetase (GS; EC 6.3.1.2). The glnD strains, which are unable to deadenylylate GS and therefore accumulate the adenylylated or less active form of the enzyme, were isolated as glutamine bradytrophs. They lack the activity of PIIA uridylyl-transferase, one of the proteins required for deadenylylation of GS; in addition, they lack PIID uridylyl-removing activity. Mutations in glnD are suppressed by second-site mutations in glnE that eliminate the activity of GS adenylyltransferase (EC 2.7.7.42) and thus prevent adenylylation of GS. The glnD and glnE strains have one-third to one-half as much total GS as the wild-type strain when they are grown in a medium containing a high concentration of NH4+. The wild-type strain derepresses synthesis of GS fourfold in response to nitrogen limitation; glnD and glnE strains derepress synthesis of the enzyme fourfold and sevenfold, respectively. Thus, mutations that alter covalent modification of GS in Salmonella do not significantly affect derepression of its synthesis. The glnD gene lies at 7 min on the Salmonella chromosome and is 50% linked to pyrH by P22-mediated transduction.", "contents": "Mutations that alter the covalent modification of glutamine synthetase in Salmonella typhimurium. glnD and glnE mutant strains of Salmonella typhimurium lack three of the four activities required for reversible covalent modification of glutamine synthetase (GS; EC 6.3.1.2). The glnD strains, which are unable to deadenylylate GS and therefore accumulate the adenylylated or less active form of the enzyme, were isolated as glutamine bradytrophs. They lack the activity of PIIA uridylyl-transferase, one of the proteins required for deadenylylation of GS; in addition, they lack PIID uridylyl-removing activity. Mutations in glnD are suppressed by second-site mutations in glnE that eliminate the activity of GS adenylyltransferase (EC 2.7.7.42) and thus prevent adenylylation of GS. The glnD and glnE strains have one-third to one-half as much total GS as the wild-type strain when they are grown in a medium containing a high concentration of NH4+. The wild-type strain derepresses synthesis of GS fourfold in response to nitrogen limitation; glnD and glnE strains derepress synthesis of the enzyme fourfold and sevenfold, respectively. Thus, mutations that alter covalent modification of GS in Salmonella do not significantly affect derepression of its synthesis. The glnD gene lies at 7 min on the Salmonella chromosome and is 50% linked to pyrH by P22-mediated transduction."}
{"id": "PMID:26664", "title": "Genetics and physiology of Neurospora crassa glutamine auxotrophs.", "content": "This work reports on the isolation and characterization of two glutamine auxotrophs in Neurospora crassa. The mutations responsible for the glutamine-requiring phenotype were very closely linked, and one of them proved to be recessive to wild type. The mutations impaired the conversion of glutamic acid to glutamine and resulted in changes of both the activity and oligomeric structure of the enzyme glutamine synthetase.", "contents": "Genetics and physiology of Neurospora crassa glutamine auxotrophs. This work reports on the isolation and characterization of two glutamine auxotrophs in Neurospora crassa. The mutations responsible for the glutamine-requiring phenotype were very closely linked, and one of them proved to be recessive to wild type. The mutations impaired the conversion of glutamic acid to glutamine and resulted in changes of both the activity and oligomeric structure of the enzyme glutamine synthetase."}
{"id": "PMID:26665", "title": "Oxidation kinetics and chemostat growth kinetics of Thiobacillus ferrooxidans on tetrathionate and thiosulfate.", "content": "Growth of Thiobacillus ferrooxidans in batch culture on 10 mM potassium tetrathionate was optimal at pH 2.5 (specific growth rate, 0.092 h-1). Oxygen electrode studies on resting cell suspensions showed that the apparent Km for tetrathionate oxidation (0.13 to 8.33 mM) was pH dependent, suggesting higher substrate affinity at higher pH. Conversely, oxidation rates were greatest at low pH. High substrate concentrations (7.7 to 77 mM) did not affect maximum oxidation rates at pH 3.0, but produced substrate inhibition at other pH values. Tetrathionate-grown cell suspensions also oxidized thiosulfate at pH 2.0 to 4.0. Apparent Km values (1.2 to 25 mM) were of the same order as for tetrathionate, but kinetics were complex. Continuous culture on growth-limiting tetrathionate at pH 2.5, followed by continuous culture on growth-limiting thiosulfate at pH 2.5, indicated true growth yield values (grams [dry weight] per gram-molecule of substrate) of 12.2 and 7.5, and maintenance coefficient values (millimoles of substrate per gram [dry weight) of organisms per hour) of 1.01 and 0.97 for tetrathionate and thiosulfate, respectively. Yield was increased on both media at low dilution rates by increase in CO2 supply. The apparent maintenance coefficient was lowered without affecting YG, suggesting better energy coupling in CO2-rich environments. Prolonged continuous cultivation on tetrathionate or thiosulfate did not affect the ability of the organism to grow subsequently in ferrous iron medium.", "contents": "Oxidation kinetics and chemostat growth kinetics of Thiobacillus ferrooxidans on tetrathionate and thiosulfate. Growth of Thiobacillus ferrooxidans in batch culture on 10 mM potassium tetrathionate was optimal at pH 2.5 (specific growth rate, 0.092 h-1). Oxygen electrode studies on resting cell suspensions showed that the apparent Km for tetrathionate oxidation (0.13 to 8.33 mM) was pH dependent, suggesting higher substrate affinity at higher pH. Conversely, oxidation rates were greatest at low pH. High substrate concentrations (7.7 to 77 mM) did not affect maximum oxidation rates at pH 3.0, but produced substrate inhibition at other pH values. Tetrathionate-grown cell suspensions also oxidized thiosulfate at pH 2.0 to 4.0. Apparent Km values (1.2 to 25 mM) were of the same order as for tetrathionate, but kinetics were complex. Continuous culture on growth-limiting tetrathionate at pH 2.5, followed by continuous culture on growth-limiting thiosulfate at pH 2.5, indicated true growth yield values (grams [dry weight] per gram-molecule of substrate) of 12.2 and 7.5, and maintenance coefficient values (millimoles of substrate per gram [dry weight) of organisms per hour) of 1.01 and 0.97 for tetrathionate and thiosulfate, respectively. Yield was increased on both media at low dilution rates by increase in CO2 supply. The apparent maintenance coefficient was lowered without affecting YG, suggesting better energy coupling in CO2-rich environments. Prolonged continuous cultivation on tetrathionate or thiosulfate did not affect the ability of the organism to grow subsequently in ferrous iron medium."}
{"id": "PMID:26666", "title": "Sodium ion-proton antiport in a marine bacterium.", "content": "Alteromonas haloplanktis ejected protons in response to a brief respiratory pulse; the rate of decay of the resulting pH change was accelerated when Na+ was present in the suspension medium. The addition of an anaerobic NaCl solution to an essentially Na+-free anaerobic bacterial suspension induced the acidification of the suspension medium. These results and others discussed provide substantial evidence for the existence of an Na+-H+ antiporter in this organism.", "contents": "Sodium ion-proton antiport in a marine bacterium. Alteromonas haloplanktis ejected protons in response to a brief respiratory pulse; the rate of decay of the resulting pH change was accelerated when Na+ was present in the suspension medium. The addition of an anaerobic NaCl solution to an essentially Na+-free anaerobic bacterial suspension induced the acidification of the suspension medium. These results and others discussed provide substantial evidence for the existence of an Na+-H+ antiporter in this organism."}
{"id": "PMID:26668", "title": "Effect of ammonium ion concentration and osmotic pressure on growth of Ureaplasma urealyticum (T-strain mycoplasma).", "content": "The effect of ammonium ion concentration and osmotic pressure on growth of Ureaplasma urealyticum type VIII was determined by using a well-buffered broth medium containing 10 mM urea. The addition of NH4Cl to the medium at concentrations up to 10 mM did not affect growth; however, addition of larger quantities progressively decreased both the specific growth rate (mu) and the maximum yield of the culture, with concentrations of 80 mM completely inhibiting growth. Addition of either 150 mM KCl or NaCl to the medium did not inhibit growth, indicating that the growth-inhibitory effect was specific to NH4+ and was neither a result of increased Cl- concentration nor increased osmotic pressure. Concentrations of NH4Cl as high as 100 mM did not affect growth of either Acholeplasma laidlawii or Mycoplasma hominis. U. urealyticum was more sensitive to osmotic pressure: osmotic pressures of 710 to 780 mosmol/kg (with KCl, NaCl, or sucrose) resulted in both a substantially lower growth rate and a 5- to 10-fold lower peak yield of organisms. Both A laidlawii and M. hominis were less sensitive to increased osmotic pressure.", "contents": "Effect of ammonium ion concentration and osmotic pressure on growth of Ureaplasma urealyticum (T-strain mycoplasma). The effect of ammonium ion concentration and osmotic pressure on growth of Ureaplasma urealyticum type VIII was determined by using a well-buffered broth medium containing 10 mM urea. The addition of NH4Cl to the medium at concentrations up to 10 mM did not affect growth; however, addition of larger quantities progressively decreased both the specific growth rate (mu) and the maximum yield of the culture, with concentrations of 80 mM completely inhibiting growth. Addition of either 150 mM KCl or NaCl to the medium did not inhibit growth, indicating that the growth-inhibitory effect was specific to NH4+ and was neither a result of increased Cl- concentration nor increased osmotic pressure. Concentrations of NH4Cl as high as 100 mM did not affect growth of either Acholeplasma laidlawii or Mycoplasma hominis. U. urealyticum was more sensitive to osmotic pressure: osmotic pressures of 710 to 780 mosmol/kg (with KCl, NaCl, or sucrose) resulted in both a substantially lower growth rate and a 5- to 10-fold lower peak yield of organisms. Both A laidlawii and M. hominis were less sensitive to increased osmotic pressure."}
{"id": "PMID:26667", "title": "Purification and characterization of a heme-containing amine dehydrogenase from Pseudomonas putida.", "content": "The primary amine dehydrogenase of Pseudomonas putida NP was purified to homogeneity as judged by polyacrylamide gel electrophoresis. Cytochrome c or an artificial electron acceptor was required for amine dehydrogenase activity. The enzyme was nonspecific, readily oxidizing primary monoamines, benzylamine, and tyramine; little or no measurable activity was detected with isoamines, L-ornithine, L-lysine, and certain diamines or polyamines. The pH optima for n-butylamine, benzylamine, and n-propylamine were 7.0, 6.5, and 7.0, respectively. The molecular weight of the enzyme was 112,000 as determined by gel filtration and 95,300 as analyzed by sedimentation equilibrium. Subunit analysis by sodium dodecyl sulfate gel electrophoresis suggested that the enzyme was composed of two nonidentical subunits with molecular weights of 58,000 and 42,000. The absorption spectrum of the purified enzyme was indicative of a hemoprotein, exhibiting absorption maxima at 277, 355, and 408 nm. Reduction with sodium dithionite or amine substrates resulted in absorption maxima at 523 and 552 nm and a shift in the Soret peak to 416 nm. These results suggested that the enzyme is a hemoprotein of the type c cytochrome. There was no evidence that flavins were present.", "contents": "Purification and characterization of a heme-containing amine dehydrogenase from Pseudomonas putida. The primary amine dehydrogenase of Pseudomonas putida NP was purified to homogeneity as judged by polyacrylamide gel electrophoresis. Cytochrome c or an artificial electron acceptor was required for amine dehydrogenase activity. The enzyme was nonspecific, readily oxidizing primary monoamines, benzylamine, and tyramine; little or no measurable activity was detected with isoamines, L-ornithine, L-lysine, and certain diamines or polyamines. The pH optima for n-butylamine, benzylamine, and n-propylamine were 7.0, 6.5, and 7.0, respectively. The molecular weight of the enzyme was 112,000 as determined by gel filtration and 95,300 as analyzed by sedimentation equilibrium. Subunit analysis by sodium dodecyl sulfate gel electrophoresis suggested that the enzyme was composed of two nonidentical subunits with molecular weights of 58,000 and 42,000. The absorption spectrum of the purified enzyme was indicative of a hemoprotein, exhibiting absorption maxima at 277, 355, and 408 nm. Reduction with sodium dithionite or amine substrates resulted in absorption maxima at 523 and 552 nm and a shift in the Soret peak to 416 nm. These results suggested that the enzyme is a hemoprotein of the type c cytochrome. There was no evidence that flavins were present."}
{"id": "PMID:26669", "title": "Organic fluorides: implications for psychiatry.", "content": "The widespread use of synthetic organic fluorides has recently received attention as a potential health hazard. There are a number of organic fluorides which have become important considerations in psychiatry. Therapeutically the organic fluorides include the neuroleptics trifluoperazine, fluphenazine, triflupromazine, and haloperidol, the benzodiazepine flurazepam and the polyfluorinated inhalant convulsant indoklon. On the negative side, deliberate inhalation of fluorocarbon aerosol propellants has become a modern form of drug abuse among the young. A review is presented on the biochemistry and toxicology of organic fluorides with special emphasis on implications to the field of psychiatry.", "contents": "Organic fluorides: implications for psychiatry. The widespread use of synthetic organic fluorides has recently received attention as a potential health hazard. There are a number of organic fluorides which have become important considerations in psychiatry. Therapeutically the organic fluorides include the neuroleptics trifluoperazine, fluphenazine, triflupromazine, and haloperidol, the benzodiazepine flurazepam and the polyfluorinated inhalant convulsant indoklon. On the negative side, deliberate inhalation of fluorocarbon aerosol propellants has become a modern form of drug abuse among the young. A review is presented on the biochemistry and toxicology of organic fluorides with special emphasis on implications to the field of psychiatry."}
{"id": "PMID:26670", "title": "Enzymatic oxidation of disulfides and thiolsulfinates by both rabbit liver microsomes and a reconstituted system with purified cytochrome P-450.", "content": "Both rabbit liver microsomes and reconstituted system with purified cytochrome P-450 and cofactors enzymatically oxidized o-dithiane (1, 2-dithiane), 3-methyl-o-dithiane, thiane and 2-methylthiane to the corresponding mono-oxygenated products; sulfides or disulfides were oxidized to the corresponding sulfoxides or thiosulfinates, while thiosulfinate was oxidized to thiolsulfonate. The reconstituted systems required oxygen and NADPH and were not affected by the catalase which decomposes H2O2, or by 1,4-diazabicyclo-[2,2,2]octane (DABCO), which is a good quencher of singlet oxygen. The differences in the binding of substrates such as sulfides and disulfides with the enzyme system are discussed in connection with differences in the spectra of the substrates in the reconstituted system with pure cytochrome P-450. A correlation was found between the rates of oxidation of the substrates and the rates of oxidation of NADPH.", "contents": "Enzymatic oxidation of disulfides and thiolsulfinates by both rabbit liver microsomes and a reconstituted system with purified cytochrome P-450. Both rabbit liver microsomes and reconstituted system with purified cytochrome P-450 and cofactors enzymatically oxidized o-dithiane (1, 2-dithiane), 3-methyl-o-dithiane, thiane and 2-methylthiane to the corresponding mono-oxygenated products; sulfides or disulfides were oxidized to the corresponding sulfoxides or thiosulfinates, while thiosulfinate was oxidized to thiolsulfonate. The reconstituted systems required oxygen and NADPH and were not affected by the catalase which decomposes H2O2, or by 1,4-diazabicyclo-[2,2,2]octane (DABCO), which is a good quencher of singlet oxygen. The differences in the binding of substrates such as sulfides and disulfides with the enzyme system are discussed in connection with differences in the spectra of the substrates in the reconstituted system with pure cytochrome P-450. A correlation was found between the rates of oxidation of the substrates and the rates of oxidation of NADPH."}
{"id": "PMID:26673", "title": "New chromogenic and fluorogenic substrates  for pyrrolidonyl peptidase.", "content": "L-Pyroglutamyl derivatives of p-nitroaniline and 7-amino-4-methylcoumarin were synthesized as new sensitive substrates for pyrrolidonyl peptidase (pyrrolidonecarboxylyl peptidase) from Bacillus amyloliquefaciens. Their hydrolyses could be followed by conventional colorimetric and fluorometric procedures; i.e., in terms of the increase in absorbance at 410 nm caused by the liberation of p-nitroaniline and the emission at 440 nm after excitation at 370 nm depending on the liberation of 7-amino-4-methylcoumarin. Values of Km were estimated to be 0.69 mM for anilide substrate and 0.33 mM for methylcoumarin substrate in the pyrrolidonyl peptidase reaction at pH 8.0. The methylcoumarin compound was about one thousand fold more sensitive than the anilide substrate.", "contents": "New chromogenic and fluorogenic substrates  for pyrrolidonyl peptidase. L-Pyroglutamyl derivatives of p-nitroaniline and 7-amino-4-methylcoumarin were synthesized as new sensitive substrates for pyrrolidonyl peptidase (pyrrolidonecarboxylyl peptidase) from Bacillus amyloliquefaciens. Their hydrolyses could be followed by conventional colorimetric and fluorometric procedures; i.e., in terms of the increase in absorbance at 410 nm caused by the liberation of p-nitroaniline and the emission at 440 nm after excitation at 370 nm depending on the liberation of 7-amino-4-methylcoumarin. Values of Km were estimated to be 0.69 mM for anilide substrate and 0.33 mM for methylcoumarin substrate in the pyrrolidonyl peptidase reaction at pH 8.0. The methylcoumarin compound was about one thousand fold more sensitive than the anilide substrate."}
{"id": "PMID:26674", "title": "Acceptor specificity of ATP:nucleoside-5'-phosphate pyrophosphotransferase from Streptomyces adephospholyticus. Synthesis of the 3'-pyrophosphates of pyrimidine nucleotides, some oligoribonucleotides, 5'-diphosphonucleosidic coenzymes and mG-5'-ppp-5'-Am.", "content": "ATP: nucleoside-5'-phosphate pyrophosphotransferase [EC 2.7.6.4] of Streptomyces adephospholyticus synthesizes not only 3'-pyrophosphates of 5'-purine ribomononucleotides but also those of pyrimidine mononucleotides, some short oligonucleotides, a variety of 5'-diphosphonucleosidic coenzymes and mG-5'-ppp-5'-Am.", "contents": "Acceptor specificity of ATP:nucleoside-5'-phosphate pyrophosphotransferase from Streptomyces adephospholyticus. Synthesis of the 3'-pyrophosphates of pyrimidine nucleotides, some oligoribonucleotides, 5'-diphosphonucleosidic coenzymes and mG-5'-ppp-5'-Am. ATP: nucleoside-5'-phosphate pyrophosphotransferase [EC 2.7.6.4] of Streptomyces adephospholyticus synthesizes not only 3'-pyrophosphates of 5'-purine ribomononucleotides but also those of pyrimidine mononucleotides, some short oligonucleotides, a variety of 5'-diphosphonucleosidic coenzymes and mG-5'-ppp-5'-Am."}
{"id": "PMID:26675", "title": "Purification and characterization of alkaline phosphatase in cultured rat liver cells.", "content": "Alkaline phosphatase has been purified from cultured rat liver cells by butanol extraction, column chromatography on DEAE-cellulose and on Sephadex G-200, and preparative polyacrylamide gel electrophoresis. By electrophoresis on polyacrylamide, the purified enzyme was resolved into two active forms. Both forms have similar molecular weights of around 200,000. The subunit size was found to be 50,000 by SDS-polyacrylamide gel electrophoresis. These results suggest that alkaline phosphatase purified from cultured rat liver cells has a tetrameric structure. The optimum pH was found to be approximately 10.4, using p-nitrophenylphosphate as a substrate in a carbonate buffer system. The apparent Km was estimated to be 2.4 mM, using p-nitrophenylphosphate in carbonate buffer, pH 10.4.", "contents": "Purification and characterization of alkaline phosphatase in cultured rat liver cells. Alkaline phosphatase has been purified from cultured rat liver cells by butanol extraction, column chromatography on DEAE-cellulose and on Sephadex G-200, and preparative polyacrylamide gel electrophoresis. By electrophoresis on polyacrylamide, the purified enzyme was resolved into two active forms. Both forms have similar molecular weights of around 200,000. The subunit size was found to be 50,000 by SDS-polyacrylamide gel electrophoresis. These results suggest that alkaline phosphatase purified from cultured rat liver cells has a tetrameric structure. The optimum pH was found to be approximately 10.4, using p-nitrophenylphosphate as a substrate in a carbonate buffer system. The apparent Km was estimated to be 2.4 mM, using p-nitrophenylphosphate in carbonate buffer, pH 10.4."}
{"id": "PMID:26676", "title": "Purification of lysophospholipase of Vibrio parahaemolyticus and its properties.", "content": "Lysophospholipase [EC 3.1.1.5] was solubilized from the cells of Vibrio parahaemolyticus with Triton X-100 and purified by the following procedure; precipitation with ammonium sulfate, acid treatment and ion exchange column chromatography using DEAE-cellulose, DEAE-Sephadex A-50, and CM-cellulose, successively. The purified preparation was shown to be homogeneous by polyacrylamide gel disk electrophoresis. The isoelectric point of the enzyme was found to be around pH 3.64 by isoelectric focusing electrophoresis, and its molecular weight was estimated to be 89,000 at pH 7.6 by gel filtration on Sephadex G-200. The minimal molecular weight (15,000) was found at pH 3 by gel filtration on Sephadex G-100 and also by SDS-polyacrylamide disk electrophoresis. The enzyme hydrolyzed 1-acyl-GPC, 1-acyl-GPE, 2-acyl-GPE, and lysocardiolipin but did not attack monoacylglycerol, triacylglycerol, or phosphatidylcholine at all. The enzyme activity required no bivalent cations, and was unaffected by reagents specific to SH-groups, although it was inhibited by Hg2+. The enzyme activity was completely inhibited by preincubation with diisopropylfluorophosphate. The enzyme lost its activity on preincubation with either 1% SDS or 8 M urea at 37 degrees C for 30 min, but the activity lost with urea was recovered by dialysis against distilled water.", "contents": "Purification of lysophospholipase of Vibrio parahaemolyticus and its properties. Lysophospholipase [EC 3.1.1.5] was solubilized from the cells of Vibrio parahaemolyticus with Triton X-100 and purified by the following procedure; precipitation with ammonium sulfate, acid treatment and ion exchange column chromatography using DEAE-cellulose, DEAE-Sephadex A-50, and CM-cellulose, successively. The purified preparation was shown to be homogeneous by polyacrylamide gel disk electrophoresis. The isoelectric point of the enzyme was found to be around pH 3.64 by isoelectric focusing electrophoresis, and its molecular weight was estimated to be 89,000 at pH 7.6 by gel filtration on Sephadex G-200. The minimal molecular weight (15,000) was found at pH 3 by gel filtration on Sephadex G-100 and also by SDS-polyacrylamide disk electrophoresis. The enzyme hydrolyzed 1-acyl-GPC, 1-acyl-GPE, 2-acyl-GPE, and lysocardiolipin but did not attack monoacylglycerol, triacylglycerol, or phosphatidylcholine at all. The enzyme activity required no bivalent cations, and was unaffected by reagents specific to SH-groups, although it was inhibited by Hg2+. The enzyme activity was completely inhibited by preincubation with diisopropylfluorophosphate. The enzyme lost its activity on preincubation with either 1% SDS or 8 M urea at 37 degrees C for 30 min, but the activity lost with urea was recovered by dialysis against distilled water."}
{"id": "PMID:26677", "title": "Studies on the formation of gamma-aminobutyric acid from putrescine in rat organs and purification of its synthetic enzyme from rat intestine.", "content": "The formation of gamma-aminobutyric acid (GABA) from putrescine was examined in organs of rats using radioactive putrescine. Radioactive GABA was detected in all the organs of a rat injected intraperitoneally with radioactive putrescine, and the highest radioactivity of GABA was observed in the small intestine. The enzyme involved in this formation was purified from small intestine and identified as a diamine oxidase, histaminase, from the properties of the enzyme. Activity of the enzyme was found in all the organs of rat, and the highest activity was observed in the small intestine.", "contents": "Studies on the formation of gamma-aminobutyric acid from putrescine in rat organs and purification of its synthetic enzyme from rat intestine. The formation of gamma-aminobutyric acid (GABA) from putrescine was examined in organs of rats using radioactive putrescine. Radioactive GABA was detected in all the organs of a rat injected intraperitoneally with radioactive putrescine, and the highest radioactivity of GABA was observed in the small intestine. The enzyme involved in this formation was purified from small intestine and identified as a diamine oxidase, histaminase, from the properties of the enzyme. Activity of the enzyme was found in all the organs of rat, and the highest activity was observed in the small intestine."}
{"id": "PMID:26678", "title": "Purification and characterization of alkaline phosphatase from plasma membranes of rat ascites hepatoma.", "content": "Alkaline phosphatase was purified from plasma membranes of rat ascites hepatoma AH-130, the homogenate of which had 50-fold higher specific activity than that found in the liver homogenate. The presence of Triton X-100, 0.5%, was essential to avoid its aggregation and to stabilize its activity. The purified enzyme, a glycoprotien, was homogeneous in polyacrylamide gel electrophoresis. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate indicated a protein molecular weight of 140,000. The addition of beta-mercaptoethanol caused the dissociation of the alkaline phosphatase into two subunits of identical molecular weight, 72,000. Isoelectric focusing revealed that the pI of this enzyme is 4.7. The pH optimum for the purified enzyme was 10.5 or higher with p-nitrophenylphosphate, and slightly lower pH values (pH 9.5--10.2) were obtained when other substrates were used. Of the substrates tested, p-nitrophenylphosphate (Km-0.3 mM) was most rapidly hydrolyzed. Vmax values of other substrates relative to that of p-nitrophenylphosphate were as follows; beta-glycerophosphate, 76%; 5'-TMP, 82%; 5'-AMP, 62%; 5'-IMP, 43%; glucose-6-phosphate, 39%; ADP, 36% and ATP, 15%. More than 90% of the activity of the purified enzyme was irreversibly lost when it was heated at 55 degrees C for 30 min, or exposed either to 10 mM beta-mercaptoethanol for 10 min to 3 M urea for 30 min, or to an acidic pH below pH 5.0 for 2 h. Of the effects by divalent cations, Mg2+ activated the enzyme by 20% whereas Zn2+ strongly inhibited it by 95% at 0.5 mM. EDTA at higher than 1 mM inactivated the enzyme irreversibly, although the effect of EDTA at lower than 0.1 mM was reversible by the addition of divalent cations, particularly by Mg2+. The enzyme was most strongly inhibited by L-histidine among the amino acids tested, and also strongly inhibited by imidazole. These results suggest that alkaline phosphatase of rat hepatoma AH-130 is very similar to that of rat liver in most of the properties reported so far.", "contents": "Purification and characterization of alkaline phosphatase from plasma membranes of rat ascites hepatoma. Alkaline phosphatase was purified from plasma membranes of rat ascites hepatoma AH-130, the homogenate of which had 50-fold higher specific activity than that found in the liver homogenate. The presence of Triton X-100, 0.5%, was essential to avoid its aggregation and to stabilize its activity. The purified enzyme, a glycoprotien, was homogeneous in polyacrylamide gel electrophoresis. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate indicated a protein molecular weight of 140,000. The addition of beta-mercaptoethanol caused the dissociation of the alkaline phosphatase into two subunits of identical molecular weight, 72,000. Isoelectric focusing revealed that the pI of this enzyme is 4.7. The pH optimum for the purified enzyme was 10.5 or higher with p-nitrophenylphosphate, and slightly lower pH values (pH 9.5--10.2) were obtained when other substrates were used. Of the substrates tested, p-nitrophenylphosphate (Km-0.3 mM) was most rapidly hydrolyzed. Vmax values of other substrates relative to that of p-nitrophenylphosphate were as follows; beta-glycerophosphate, 76%; 5'-TMP, 82%; 5'-AMP, 62%; 5'-IMP, 43%; glucose-6-phosphate, 39%; ADP, 36% and ATP, 15%. More than 90% of the activity of the purified enzyme was irreversibly lost when it was heated at 55 degrees C for 30 min, or exposed either to 10 mM beta-mercaptoethanol for 10 min to 3 M urea for 30 min, or to an acidic pH below pH 5.0 for 2 h. Of the effects by divalent cations, Mg2+ activated the enzyme by 20% whereas Zn2+ strongly inhibited it by 95% at 0.5 mM. EDTA at higher than 1 mM inactivated the enzyme irreversibly, although the effect of EDTA at lower than 0.1 mM was reversible by the addition of divalent cations, particularly by Mg2+. The enzyme was most strongly inhibited by L-histidine among the amino acids tested, and also strongly inhibited by imidazole. These results suggest that alkaline phosphatase of rat hepatoma AH-130 is very similar to that of rat liver in most of the properties reported so far."}
{"id": "PMID:26679", "title": "Monomer-dimer equilibria of a Bence Jones protein and its variable fragment.", "content": "The circular dichroic (CD) spectra of a type lambda Bence Jones protein (Tod), its variable (VL) fragment, and the constant (CL) fragment of a type lambda protein (Nag) were measured under various conditions. In the pH region from 5.5 to 7.5, the CD spectra of Tod protein with intact interchain disulfide bond (L(SS)) and and CL did not change with pH, while the spectra of Tod protein in which the interchain disulfide bond had been reduced and alkylated (L(RA)) and VL did not change with pH. The dimerization reactions of L(RA) and VL were studied by following the CD change with protein concentration. The CD spectrum of CL did not change with the protein concentration. The dimerization constant for L(RA) was 4 X 10(4) M-1 at at pH 7.5 and 25 degrees C, which was smaller than that for VL (1 X 10(5) M-1). The ellipticity at 278 nm for the L(RA) dimer was different from that for the L(SS) dimer and changed with pH. These findings indicate that the L(RA) dimer and L(SS) dimer have different conformations. The differences in the conformation and L-L interaction between the L(RA) dimer and L(SS) dimer are discussed on the basis of the conformations of VL and CL and the interactions between the paired domains.", "contents": "Monomer-dimer equilibria of a Bence Jones protein and its variable fragment. The circular dichroic (CD) spectra of a type lambda Bence Jones protein (Tod), its variable (VL) fragment, and the constant (CL) fragment of a type lambda protein (Nag) were measured under various conditions. In the pH region from 5.5 to 7.5, the CD spectra of Tod protein with intact interchain disulfide bond (L(SS)) and and CL did not change with pH, while the spectra of Tod protein in which the interchain disulfide bond had been reduced and alkylated (L(RA)) and VL did not change with pH. The dimerization reactions of L(RA) and VL were studied by following the CD change with protein concentration. The CD spectrum of CL did not change with the protein concentration. The dimerization constant for L(RA) was 4 X 10(4) M-1 at at pH 7.5 and 25 degrees C, which was smaller than that for VL (1 X 10(5) M-1). The ellipticity at 278 nm for the L(RA) dimer was different from that for the L(SS) dimer and changed with pH. These findings indicate that the L(RA) dimer and L(SS) dimer have different conformations. The differences in the conformation and L-L interaction between the L(RA) dimer and L(SS) dimer are discussed on the basis of the conformations of VL and CL and the interactions between the paired domains."}
{"id": "PMID:26680", "title": "A novel magnesium-independent neutral sphingomyelinase associated with rat central nervous system meylin.", "content": "Purified myelin fractions prepared from young adult rat brain contain a novel sphingomyelinase which has a pH optimum of 7.0 and does not require divalent cations. This sphingomyelinase is different from the two previously known sphingomyelinases in the brain--the acidic sphingomyelinase and the magnesium-dependent neutral sphingomyelinase. When the distributions of the sphingomyelinases among the purified myelin, the total subcellular fractions heavier than myelin (greater than 0.85 M sucrose), and the microsomes were examined, the magnesium-independent sphingomyelinase was detected only in myelin, while the magnesium-dependent sphingomyelinase was present in the other two fractions but not in myelin. Therefore, this new sphingomyelinase appears to be specifically localized in the myelin sheath.", "contents": "A novel magnesium-independent neutral sphingomyelinase associated with rat central nervous system meylin. Purified myelin fractions prepared from young adult rat brain contain a novel sphingomyelinase which has a pH optimum of 7.0 and does not require divalent cations. This sphingomyelinase is different from the two previously known sphingomyelinases in the brain--the acidic sphingomyelinase and the magnesium-dependent neutral sphingomyelinase. When the distributions of the sphingomyelinases among the purified myelin, the total subcellular fractions heavier than myelin (greater than 0.85 M sucrose), and the microsomes were examined, the magnesium-independent sphingomyelinase was detected only in myelin, while the magnesium-dependent sphingomyelinase was present in the other two fractions but not in myelin. Therefore, this new sphingomyelinase appears to be specifically localized in the myelin sheath."}
{"id": "PMID:26682", "title": "3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase. Purification and molecular characterization of the phenylalanine-sensitive isoenzyme from Escherichia coli.", "content": "The phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate lyase (pyruvate phosphorylating), EC 4.2.1.15) was purified to apparent homogeneity from extracts of Escherichia coli K12. The enzyme has a molecular weight of 140,000 as judged by gel filtration and sedimentation equilibrium analysis. The enzyme has a subunit molecular weight of 35,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, suggesting that the native form of the enzyme is a tetramer. This was confirmed by cross-linking the enzyme with dimethylsuberimidate and by analyzing the cross-linked material by gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme shows a narrow pH optimum between pH 6.5 and 7.0. The enzyme is stable for several months when stored at -20 degrees C in buffers containing phosphoenolpyruvate. Removal of phosphoenolpyruvate causes an irreversible inactivation of the enzyme. The enzyme is strongly inhibited by L-phenylalanine and to a lesser degree by dihydrophenylalanine. Molecular parameters of the previously isolated tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from E. coli (Schoner, R., and Herrmann, K.M. (1976) J. Biol. Chem. 251, 5440-5447) are compared with those of the phenylalanine-sensitive isoenzyme from the same organism.", "contents": "3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase. Purification and molecular characterization of the phenylalanine-sensitive isoenzyme from Escherichia coli. The phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (7-phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose-4-phosphate lyase (pyruvate phosphorylating), EC 4.2.1.15) was purified to apparent homogeneity from extracts of Escherichia coli K12. The enzyme has a molecular weight of 140,000 as judged by gel filtration and sedimentation equilibrium analysis. The enzyme has a subunit molecular weight of 35,000 as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, suggesting that the native form of the enzyme is a tetramer. This was confirmed by cross-linking the enzyme with dimethylsuberimidate and by analyzing the cross-linked material by gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme shows a narrow pH optimum between pH 6.5 and 7.0. The enzyme is stable for several months when stored at -20 degrees C in buffers containing phosphoenolpyruvate. Removal of phosphoenolpyruvate causes an irreversible inactivation of the enzyme. The enzyme is strongly inhibited by L-phenylalanine and to a lesser degree by dihydrophenylalanine. Molecular parameters of the previously isolated tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from E. coli (Schoner, R., and Herrmann, K.M. (1976) J. Biol. Chem. 251, 5440-5447) are compared with those of the phenylalanine-sensitive isoenzyme from the same organism."}
{"id": "PMID:26685", "title": "The protonmotive force and beta-galactoside transport in Bacillus acidocaldarius.", "content": "The acidophilic and thermophilic bacterium, Bacillus acidocaldarius maintains a cytoplasmic pH between 5.85 and 6.31 over a range of external pH from 2.0 to 4.5. Consistently, the pH optimum of beta-galactosidase, as assayed in cell extracts, is between pH 6.0 and 6.5. An electrical potential (delta-psi), interior positive, is also maintained across the membrane. A delta-psi of approximately 34 mV was calculated from determinations of thiocyanate uptake by cells at pH 3.5. Addition of the proton conductor carbonyl cyanide m-chlorophenylhydrazone increased the delta-psi. Treatment of cells with valinomycin (in the absence of external potassium ions) or high concentrations of thiocyanate, to abolish the delta psi, resulted in collapse of the transmembrane proton gradient (delta pH). Active transport of methylthio-beta, D-galactoside occurred optimally at pH 3.5. Transport of the galactoside was inhibited by various compounds which could dissipate the transmembrane delta pH and by respiratory inhibitors. A decrease in the delta pH and an increase in the delta psi occurred upon addition of methylthio-beta, D-galactoside to cells of B. acidocaldarius. Thus the transport of this solute appears to involve an electrogenic symport with protons. The transport system is most active at 50 degrees C and shows little activity at 25 degrees C, although the delta pH is the same at the two temperatures. Gramicidin inhibits methylthio-beta, D-galactoside transport equally effectively at 50 degrees C and 25 degrees C, while nigericin inhibits only after a lag at 25 degrees C.", "contents": "The protonmotive force and beta-galactoside transport in Bacillus acidocaldarius. The acidophilic and thermophilic bacterium, Bacillus acidocaldarius maintains a cytoplasmic pH between 5.85 and 6.31 over a range of external pH from 2.0 to 4.5. Consistently, the pH optimum of beta-galactosidase, as assayed in cell extracts, is between pH 6.0 and 6.5. An electrical potential (delta-psi), interior positive, is also maintained across the membrane. A delta-psi of approximately 34 mV was calculated from determinations of thiocyanate uptake by cells at pH 3.5. Addition of the proton conductor carbonyl cyanide m-chlorophenylhydrazone increased the delta-psi. Treatment of cells with valinomycin (in the absence of external potassium ions) or high concentrations of thiocyanate, to abolish the delta psi, resulted in collapse of the transmembrane proton gradient (delta pH). Active transport of methylthio-beta, D-galactoside occurred optimally at pH 3.5. Transport of the galactoside was inhibited by various compounds which could dissipate the transmembrane delta pH and by respiratory inhibitors. A decrease in the delta pH and an increase in the delta psi occurred upon addition of methylthio-beta, D-galactoside to cells of B. acidocaldarius. Thus the transport of this solute appears to involve an electrogenic symport with protons. The transport system is most active at 50 degrees C and shows little activity at 25 degrees C, although the delta pH is the same at the two temperatures. Gramicidin inhibits methylthio-beta, D-galactoside transport equally effectively at 50 degrees C and 25 degrees C, while nigericin inhibits only after a lag at 25 degrees C."}
{"id": "PMID:26686", "title": "The effect of pH on the cooperative behavior of aspartate transcarbamylase from Escherichia coli.", "content": "Saturation curves of activity versus concentration were determined for aspartate transcarbamylase from Escherichia coli (EC 2.1.3.2) for the substrate L-aspartate at saturating carbamyl phosphate (4.8 mM) in buffered solution at pH values from 6.0 to 12.0. Hill coefficients were obtained from the sigmoidal curves. At pH values from 7.8 to 9.1, where substrate inhibition causes difficulties in the Hill approximation, our kinetic scheme includes substrate inhibition and residual activity in the abortive enzyme-substrate complex. The plot of Hill coefficient versus pH has pKalpha values of 7.4 and 9.8 at the half-maximum positions of the curve which has a plateau from pH 8.1 to 9.1. These pKalpha values may be associated with functional groups involved in the allosteric transition which activates the enzyme. A plot of [S]0.5 versus pH shows a pKalpha of 8.5, which may belong to a residue either at or near the aspartate binding site. At 50 mM aspartate concentration the pH-rate profile shows maxima at pH values of 8.8 and 10.0 (cf. Weitzman, P.D.J., and Wilson, I.B.(1966)J. Biol. Chem. 2418 5481-5488, who used 100 mM aspartate). However, when the pH-dependent substrate inhibition is included, the calculated Vmax--H curve is bell-shaped like that of the isolated catalytic subunit.", "contents": "The effect of pH on the cooperative behavior of aspartate transcarbamylase from Escherichia coli. Saturation curves of activity versus concentration were determined for aspartate transcarbamylase from Escherichia coli (EC 2.1.3.2) for the substrate L-aspartate at saturating carbamyl phosphate (4.8 mM) in buffered solution at pH values from 6.0 to 12.0. Hill coefficients were obtained from the sigmoidal curves. At pH values from 7.8 to 9.1, where substrate inhibition causes difficulties in the Hill approximation, our kinetic scheme includes substrate inhibition and residual activity in the abortive enzyme-substrate complex. The plot of Hill coefficient versus pH has pKalpha values of 7.4 and 9.8 at the half-maximum positions of the curve which has a plateau from pH 8.1 to 9.1. These pKalpha values may be associated with functional groups involved in the allosteric transition which activates the enzyme. A plot of [S]0.5 versus pH shows a pKalpha of 8.5, which may belong to a residue either at or near the aspartate binding site. At 50 mM aspartate concentration the pH-rate profile shows maxima at pH values of 8.8 and 10.0 (cf. Weitzman, P.D.J., and Wilson, I.B.(1966)J. Biol. Chem. 2418 5481-5488, who used 100 mM aspartate). However, when the pH-dependent substrate inhibition is included, the calculated Vmax--H curve is bell-shaped like that of the isolated catalytic subunit."}
{"id": "PMID:26687", "title": "Indoleamine 2,3-dioxygenase. Purification and some properties.", "content": "Indoleamine 2,3-dioxygenase was purified from rabbit small intestine to apparent homogeneity as judged by polyacrylamide gel electrophoresis and analytical ultracentrifugation. The native enzyme was a monomeric protein of a molecular weight of 41,000 +/- 1,000 with an s020,w value of 3.45 S. It had a relative abundance of hydrophobic amino acids such as valine, leucine, and isoleucine, and contained approximately 5% carbohydrate by weight. The estimated content of sugar residues per mol of enzyme was: galactose, 1.2; mannose, 2.6; N-acetylglucosamine, 5.2; and sialic acid, 0.8. One mole of enzyme had 0.8 mol of protoheme IX as a prosthetic group. However, copper was not detected in a significant amount and the ratio of copper to heme was less than 0.03. EPR spectra of the nitric oxide complex of the ferrous enzyme indicated that a nitrogen atom, possibly in an imidazole group, might be coordinated as the fifth ligand of the heme coenzyme. The anisotropic g values were gx = 2.08, gy = 1.98, and gz = 2.01. A single enzyme protein catalyzed the oxygenative ring cleavage of D- and L-tryptophan, D- and L-5-hydroxytryptophan, tryptamine, and serotonin. In addition, the purified enzyme had a peroxidase activity with guaiacol and potassium iodide as hydrogen donors, but not a catalase activity.", "contents": "Indoleamine 2,3-dioxygenase. Purification and some properties. Indoleamine 2,3-dioxygenase was purified from rabbit small intestine to apparent homogeneity as judged by polyacrylamide gel electrophoresis and analytical ultracentrifugation. The native enzyme was a monomeric protein of a molecular weight of 41,000 +/- 1,000 with an s020,w value of 3.45 S. It had a relative abundance of hydrophobic amino acids such as valine, leucine, and isoleucine, and contained approximately 5% carbohydrate by weight. The estimated content of sugar residues per mol of enzyme was: galactose, 1.2; mannose, 2.6; N-acetylglucosamine, 5.2; and sialic acid, 0.8. One mole of enzyme had 0.8 mol of protoheme IX as a prosthetic group. However, copper was not detected in a significant amount and the ratio of copper to heme was less than 0.03. EPR spectra of the nitric oxide complex of the ferrous enzyme indicated that a nitrogen atom, possibly in an imidazole group, might be coordinated as the fifth ligand of the heme coenzyme. The anisotropic g values were gx = 2.08, gy = 1.98, and gz = 2.01. A single enzyme protein catalyzed the oxygenative ring cleavage of D- and L-tryptophan, D- and L-5-hydroxytryptophan, tryptamine, and serotonin. In addition, the purified enzyme had a peroxidase activity with guaiacol and potassium iodide as hydrogen donors, but not a catalase activity."}
{"id": "PMID:26689", "title": "Isolation of plasma and nuclear membranes of thymocytes. I. Enzymatic composition and ultrastructure.", "content": "The purpose of this work was to isolate thymocyte plasma membranes at high yield and purity to study specific surface molecules in their structural context. A procedure was developed in which 92-95% of the cells were disrupted by homogenization in a dense viscous medium, while nuclei remained intact. Differential centrifugation of the homogenate was avoided; instead, only a brief (2 h) centrifugation at equilibrium-density of membrane components was used. Five fractions were obtained, three by flotation. Membrane-bound enzymatic activities indicated a 60-80% yield of plasma membranes in the three floated membrane fractions, which comprised 1.6% of the homogenate protein. Enrichment factors for three ectoenzymes, alkaline phosphatase, gamma-glutamyltransferase, and ouabain-sensitive adenosine triphosphatase were respectively, 70-74, and 40-50 in the two lightest fractions. Nuclear membranes were then isolated from the remaining whole nuclei and were found to be enriched in esterase and NADH-cytochrome c reductase. Plasma membranes and light nuclear membranes appeared as pure unit-membrane vesicles in thin sections and freeze-etching electron microscopy. Some aggregation of intramembranous particles occurred in plasma membrane vesicles.", "contents": "Isolation of plasma and nuclear membranes of thymocytes. I. Enzymatic composition and ultrastructure. The purpose of this work was to isolate thymocyte plasma membranes at high yield and purity to study specific surface molecules in their structural context. A procedure was developed in which 92-95% of the cells were disrupted by homogenization in a dense viscous medium, while nuclei remained intact. Differential centrifugation of the homogenate was avoided; instead, only a brief (2 h) centrifugation at equilibrium-density of membrane components was used. Five fractions were obtained, three by flotation. Membrane-bound enzymatic activities indicated a 60-80% yield of plasma membranes in the three floated membrane fractions, which comprised 1.6% of the homogenate protein. Enrichment factors for three ectoenzymes, alkaline phosphatase, gamma-glutamyltransferase, and ouabain-sensitive adenosine triphosphatase were respectively, 70-74, and 40-50 in the two lightest fractions. Nuclear membranes were then isolated from the remaining whole nuclei and were found to be enriched in esterase and NADH-cytochrome c reductase. Plasma membranes and light nuclear membranes appeared as pure unit-membrane vesicles in thin sections and freeze-etching electron microscopy. Some aggregation of intramembranous particles occurred in plasma membrane vesicles."}
{"id": "PMID:26690", "title": "Localization of D-amino acid oxidase on the cell surface of human polymorphonuclear leukocytes.", "content": "The ultrastructural localization of D-amino acid oxidase (DAO) was studied cytochemically by detecting sites of hydrogen peroxide production in human polymorphonuclear leukocytes (PMNs). Reaction product, which forms when cerous ions react with H2O2 to form an electron-dense precipitate, was demonstrated on the cell surface and within the phagosomes of phagocytically stimulated cells when D-amino acids were provided as substrate. Resting cells showed only slight activity. The competitive inhibitor D,L-2-hydroxybutyrate greatly reduced the D-amino acid-stimulated reaction while KCN did not. The cell surface reaction was abolished by nonpenetrating inhibitors of enzyme activity while that within the phagosome was not eliminated. Dense accumulations of reaction product were formed in cells which phagocytosed Staphylococcus aureus in the absence of exogenous substrate. No reaction product formed with Proteus vulgaris while an intermediate amount formed when Escherichia coli were phagocytosed. Variation in the amount of reaction product with the different bacteria correlated with the levels of D-amino acids in the bacterial cell walls which are available for the DAO of PMNs. An alternative approach utilizing ferricyanide as an electron acceptor was also used. This technique verified the results obtained with the cerium reaction, i.e., the DAO is located in the cell surface and is internalized during phagocytosis and is capable of H2O2 production within the phagosome. The present finding that DAO is localized on the cell surface further supports the concept that the plasma membrane is involved in peroxide formation in PMNs.", "contents": "Localization of D-amino acid oxidase on the cell surface of human polymorphonuclear leukocytes. The ultrastructural localization of D-amino acid oxidase (DAO) was studied cytochemically by detecting sites of hydrogen peroxide production in human polymorphonuclear leukocytes (PMNs). Reaction product, which forms when cerous ions react with H2O2 to form an electron-dense precipitate, was demonstrated on the cell surface and within the phagosomes of phagocytically stimulated cells when D-amino acids were provided as substrate. Resting cells showed only slight activity. The competitive inhibitor D,L-2-hydroxybutyrate greatly reduced the D-amino acid-stimulated reaction while KCN did not. The cell surface reaction was abolished by nonpenetrating inhibitors of enzyme activity while that within the phagosome was not eliminated. Dense accumulations of reaction product were formed in cells which phagocytosed Staphylococcus aureus in the absence of exogenous substrate. No reaction product formed with Proteus vulgaris while an intermediate amount formed when Escherichia coli were phagocytosed. Variation in the amount of reaction product with the different bacteria correlated with the levels of D-amino acids in the bacterial cell walls which are available for the DAO of PMNs. An alternative approach utilizing ferricyanide as an electron acceptor was also used. This technique verified the results obtained with the cerium reaction, i.e., the DAO is located in the cell surface and is internalized during phagocytosis and is capable of H2O2 production within the phagosome. The present finding that DAO is localized on the cell surface further supports the concept that the plasma membrane is involved in peroxide formation in PMNs."}
{"id": "PMID:26691", "title": "A simplified assay of furosemide in plasma and urine by high-pressure liquid chromatography.", "content": "A simplified high-pressure liquid chromatograhic method for determination of furosemide in plasma and urine has been developed using a fluorometric detector directly coupled to the column effluent. The method includes an ether extraction from acidified biologic samples. The mobile phase used for chromatography on a reversed-phase column (C15 hydrocarbon permanently bonded to silica particles) is sufficiently acidic to induce fluorescence of furosemide. The methylester of furosemide is employed as an internal standard. The sensitivity is 0.1 and 0.25 microgram per ml plasma and urine, respectively. The applicability to pharmacokinetic studies of furosemide is shown.", "contents": "A simplified assay of furosemide in plasma and urine by high-pressure liquid chromatography. A simplified high-pressure liquid chromatograhic method for determination of furosemide in plasma and urine has been developed using a fluorometric detector directly coupled to the column effluent. The method includes an ether extraction from acidified biologic samples. The mobile phase used for chromatography on a reversed-phase column (C15 hydrocarbon permanently bonded to silica particles) is sufficiently acidic to induce fluorescence of furosemide. The methylester of furosemide is employed as an internal standard. The sensitivity is 0.1 and 0.25 microgram per ml plasma and urine, respectively. The applicability to pharmacokinetic studies of furosemide is shown."}
{"id": "PMID:26692", "title": "High-voltage paper electrophoretic assay for guanyl cyclase.", "content": "A simple, sensitive and rapid technique is described, permitting separation of cGMP from GMP, GDP and GTP by the use of unidirectional high-voltage paper electrophoresis. The recovery of labeled cGMP in the assay of guanyl cyclase, by this procedure is 85-90%; the blank values (no enzyme) are negligible.", "contents": "High-voltage paper electrophoretic assay for guanyl cyclase. A simple, sensitive and rapid technique is described, permitting separation of cGMP from GMP, GDP and GTP by the use of unidirectional high-voltage paper electrophoresis. The recovery of labeled cGMP in the assay of guanyl cyclase, by this procedure is 85-90%; the blank values (no enzyme) are negligible."}
{"id": "PMID:26693", "title": "Gentamicin-blood agar for isolation of Streptococcus pneumoniae from respiratory secretions.", "content": "Previous studies have suggested that the yield of Streptococcus pneumoniae from respiratory secretions can be increased by using a 5% sheep blood agar plate supplemented with 5 microgram of gentamicin (GBA) per ml. We report our experience with 245 lower respiratory specimens in which this method was compared with 5% sheep blood agar (SBA) alone. Of 35 specimens with growth of S. pneumoniae on either plate, 21 were detected exclusively on SBA, whereas only 3 were detected on GBA alone (P less than 0.01). By subculturing representative alpha-hemolytic colonies from the final 169 specimens, the yield of S. pneumoniae was increased by 27% compared with the number of identifications that could be made directly from the primary culture. Minimal inhibitory concentrations of gentamicin for the last 25 isolates were greater than or equal to 8 microgram/ml. Our results do not substantiate the previous observations that S. pneumoniae from respiratory secretions gives an increased yield in cultures on GBA.", "contents": "Gentamicin-blood agar for isolation of Streptococcus pneumoniae from respiratory secretions. Previous studies have suggested that the yield of Streptococcus pneumoniae from respiratory secretions can be increased by using a 5% sheep blood agar plate supplemented with 5 microgram of gentamicin (GBA) per ml. We report our experience with 245 lower respiratory specimens in which this method was compared with 5% sheep blood agar (SBA) alone. Of 35 specimens with growth of S. pneumoniae on either plate, 21 were detected exclusively on SBA, whereas only 3 were detected on GBA alone (P less than 0.01). By subculturing representative alpha-hemolytic colonies from the final 169 specimens, the yield of S. pneumoniae was increased by 27% compared with the number of identifications that could be made directly from the primary culture. Minimal inhibitory concentrations of gentamicin for the last 25 isolates were greater than or equal to 8 microgram/ml. Our results do not substantiate the previous observations that S. pneumoniae from respiratory secretions gives an increased yield in cultures on GBA."}
{"id": "PMID:26694", "title": "Diagnosis of pneumococcal pneumonia by antigen detection in sputum.", "content": "Pneumococcal polysaccharide was detected by counterimmunoelectrophoresis in the sputum of 20 of 26 (77%) adults with community-acquired pneumonia and a positive sputum culture for Streptococcus pneumoniae. The test was negative in 29 pneumonia patients with negative sputum culture for S. pneumoniae. Pneumococcal antigen was also detected in the sputum of six of nine adults with chronic bronchitis and a positive sputum culture, but was not detected in expectorated respiratory secretions of 22 pneumococcal carriers with colds. Pneumococcal antigen could also be detected in sputum by immunodiffusion; antigen titers varied from 1:2 to 1:256. These results strongly suggest that the detection of pneumococcal antigen in respiratory tract secretions indicates infection caused by S. pneumoniae.", "contents": "Diagnosis of pneumococcal pneumonia by antigen detection in sputum. Pneumococcal polysaccharide was detected by counterimmunoelectrophoresis in the sputum of 20 of 26 (77%) adults with community-acquired pneumonia and a positive sputum culture for Streptococcus pneumoniae. The test was negative in 29 pneumonia patients with negative sputum culture for S. pneumoniae. Pneumococcal antigen was also detected in the sputum of six of nine adults with chronic bronchitis and a positive sputum culture, but was not detected in expectorated respiratory secretions of 22 pneumococcal carriers with colds. Pneumococcal antigen could also be detected in sputum by immunodiffusion; antigen titers varied from 1:2 to 1:256. These results strongly suggest that the detection of pneumococcal antigen in respiratory tract secretions indicates infection caused by S. pneumoniae."}
{"id": "PMID:26695", "title": "Superoxide generation by digitonin-stimulated guinea pig granulocytes. A basis for a continuous assay for monitoring superoxide production and for the study of the activation of the generating system.", "content": "Stimulation of guinea pig granolocytes by digitonin results in superoxide (O-2) generation. A continuous assay shows that there is a lag between the addition of digitonin and the onset of O-2 production. The rate of activation of the O-2 generating system is dependent upon the concentration of digitonin and the temperature. The final linear rate of O-2 production is affected by the concentration of digitonin, temperature, pH, and the presence of exogenous reduced pyridine nucleotides. Thus, factors which alter either the activation process or the activity of the O-2 generating system can affect O-2 production by stimulated granolocytes.", "contents": "Superoxide generation by digitonin-stimulated guinea pig granulocytes. A basis for a continuous assay for monitoring superoxide production and for the study of the activation of the generating system. Stimulation of guinea pig granolocytes by digitonin results in superoxide (O-2) generation. A continuous assay shows that there is a lag between the addition of digitonin and the onset of O-2 production. The rate of activation of the O-2 generating system is dependent upon the concentration of digitonin and the temperature. The final linear rate of O-2 production is affected by the concentration of digitonin, temperature, pH, and the presence of exogenous reduced pyridine nucleotides. Thus, factors which alter either the activation process or the activity of the O-2 generating system can affect O-2 production by stimulated granolocytes."}
{"id": "PMID:26696", "title": "Inhibition of the bicarbonate exit step in urinary acidification by a disulfonic stilbene.", "content": "Acidification of the luminal solution by the isolated turtle bladder involves H(+) secretion by a pump at the luminal membrane. The OH(-) dissociated in this process reacts with CO(2) and forms HCO(3) (-) which moves passively out of the cell across the serosal cell membrane. In the present study, this exit step for HCO(3) (-) was inhibited by serosal addition of the disulfonic stilbene, SITS, an agent which is thought to bind to a transport protein at the serosal cell membrane. 90 min after serosal addition of 0.5 mM SITS, H(+) secretion decreased by > 80%. In contrast, luminal addition of SITS had no effect. During inhibition of H(+) secretion by serosal SITS, overall cell pH, measured by the 5, 5-dimethyl-2, 3-oxazolidinedione method, increased from 7.48+/-0.03 to 7.61+/-0.02. This increase of 0.13+/-0.02 pH U was associated with a much larger regional pH increase as judged from the decrement in the attainable pH gradient across the epithelium. After serosal SITS, this gradient was reduced from 2.88+/-0.06 to 2.09+/-0.11 pH U. In the absence of evidence for increased H(+) permeability or a change in the force of the H(+) pump, the gradient decrement of 0.79+/-0.08 U reflects a similar pH increment on the cytoplasmic side of the pump.SITS inhibits the exit of bicarbonate across the serosal cell membrane and, thereby, creates a compartment of high alkalinity in series with the pump. The increased electrochemical gradient across the active transport pathway is the primary factor in the inhibition of urinary acidification.", "contents": "Inhibition of the bicarbonate exit step in urinary acidification by a disulfonic stilbene. Acidification of the luminal solution by the isolated turtle bladder involves H(+) secretion by a pump at the luminal membrane. The OH(-) dissociated in this process reacts with CO(2) and forms HCO(3) (-) which moves passively out of the cell across the serosal cell membrane. In the present study, this exit step for HCO(3) (-) was inhibited by serosal addition of the disulfonic stilbene, SITS, an agent which is thought to bind to a transport protein at the serosal cell membrane. 90 min after serosal addition of 0.5 mM SITS, H(+) secretion decreased by > 80%. In contrast, luminal addition of SITS had no effect. During inhibition of H(+) secretion by serosal SITS, overall cell pH, measured by the 5, 5-dimethyl-2, 3-oxazolidinedione method, increased from 7.48+/-0.03 to 7.61+/-0.02. This increase of 0.13+/-0.02 pH U was associated with a much larger regional pH increase as judged from the decrement in the attainable pH gradient across the epithelium. After serosal SITS, this gradient was reduced from 2.88+/-0.06 to 2.09+/-0.11 pH U. In the absence of evidence for increased H(+) permeability or a change in the force of the H(+) pump, the gradient decrement of 0.79+/-0.08 U reflects a similar pH increment on the cytoplasmic side of the pump.SITS inhibits the exit of bicarbonate across the serosal cell membrane and, thereby, creates a compartment of high alkalinity in series with the pump. The increased electrochemical gradient across the active transport pathway is the primary factor in the inhibition of urinary acidification."}
{"id": "PMID:26697", "title": "An androgen binding protein in the testicular cytosol of human testis. Comparison with human plasma testosterone-estrogen binding globulin.", "content": "After removal of plasma contamination, an androgen binding protein (hABP) was detected in a 105,000-g supernate of human testicular homogenate. The physicochemical properties of hABP have been compared with a similar androgen binding protein in human plasma, testosterone-estrogen binding globulin (TeBG). hABP had high affinity (K(d) = 7.8 nM) and low capacity (0.27 pmol/mg protein) for 5alpha-dihydrotestosterone (DHT). Binding affinity of human TeBG for DHT was greater (K(d) = 0.66 nM, binding capacity 0.68 pmol/mg protein). On the basis of sedimentation rates and Einstein Stokes radii of hABP and TeBG, the mol wt of the two proteins were similar in the range of 87,000-92,000. The ligand specificities of hABP and TeBG were the same. The binding of [(3)H]DHT to hABP and TeBG were reversible processes at 0 degrees C. The half-lives for the dissociation of [(3)H]DHT from hABP and TeBG were 100-120 min and 67-70 min, respectively. Heat sensitivity of hABP and TeBG were similar. hABP had a sharp pH binding curve with an optimum at 8, whereas TeBG had a stable pH optimum between 6.5 and 9. hABP and TeBG were eluted from an ion exchange column at 100 mM and 80 mM sodium chloride concentrations, respectively. Concanavalin A and ricin Sepharose affinity chromatography showed that TeBG is bound to the columns nearly quantitatively, whereas hABP is bound to the columns only partially. Differences between hABP and TeBG, plus the reduction of plasma contamination as marked by albumin, suggest that the human mature testis contains an androgen binding protein separate from that circulating in plasma.", "contents": "An androgen binding protein in the testicular cytosol of human testis. Comparison with human plasma testosterone-estrogen binding globulin. After removal of plasma contamination, an androgen binding protein (hABP) was detected in a 105,000-g supernate of human testicular homogenate. The physicochemical properties of hABP have been compared with a similar androgen binding protein in human plasma, testosterone-estrogen binding globulin (TeBG). hABP had high affinity (K(d) = 7.8 nM) and low capacity (0.27 pmol/mg protein) for 5alpha-dihydrotestosterone (DHT). Binding affinity of human TeBG for DHT was greater (K(d) = 0.66 nM, binding capacity 0.68 pmol/mg protein). On the basis of sedimentation rates and Einstein Stokes radii of hABP and TeBG, the mol wt of the two proteins were similar in the range of 87,000-92,000. The ligand specificities of hABP and TeBG were the same. The binding of [(3)H]DHT to hABP and TeBG were reversible processes at 0 degrees C. The half-lives for the dissociation of [(3)H]DHT from hABP and TeBG were 100-120 min and 67-70 min, respectively. Heat sensitivity of hABP and TeBG were similar. hABP had a sharp pH binding curve with an optimum at 8, whereas TeBG had a stable pH optimum between 6.5 and 9. hABP and TeBG were eluted from an ion exchange column at 100 mM and 80 mM sodium chloride concentrations, respectively. Concanavalin A and ricin Sepharose affinity chromatography showed that TeBG is bound to the columns nearly quantitatively, whereas hABP is bound to the columns only partially. Differences between hABP and TeBG, plus the reduction of plasma contamination as marked by albumin, suggest that the human mature testis contains an androgen binding protein separate from that circulating in plasma."}
{"id": "PMID:26702", "title": "Relationship between phosphorylation of tyrosine aminotransferase and regulation of its synthesis by cyclic AMP and hormones.", "content": "Tyrosine adminotransferase (EC 2.6.1.5) has been found to be phosphorylated in intact rat hepatoma cells in culture. Incorporation of [32p]i into the enzyme is rapid and is exclusively found as phosphoserine. Cycloheximide treatment reduced phosphorylation of the aminotransferase only slightly and in the presence of three different inducers of this enzyme, dexamethasone, insulin, and dibutyryl cyclic AMP, [32P]I incorporation was increased. It is concluded that [32p]i incorporation into this enzyme probably reflects turnover of phosphate groups associated with pre-existing enzyme molecules catalyzed by a cyclic AMP-independent protein kinase.", "contents": "Relationship between phosphorylation of tyrosine aminotransferase and regulation of its synthesis by cyclic AMP and hormones. Tyrosine adminotransferase (EC 2.6.1.5) has been found to be phosphorylated in intact rat hepatoma cells in culture. Incorporation of [32p]i into the enzyme is rapid and is exclusively found as phosphoserine. Cycloheximide treatment reduced phosphorylation of the aminotransferase only slightly and in the presence of three different inducers of this enzyme, dexamethasone, insulin, and dibutyryl cyclic AMP, [32P]I incorporation was increased. It is concluded that [32p]i incorporation into this enzyme probably reflects turnover of phosphate groups associated with pre-existing enzyme molecules catalyzed by a cyclic AMP-independent protein kinase."}
{"id": "PMID:26703", "title": "The stimulation by catecholamines of guanylate cyclase activity in a cell-free system.", "content": "Cytosolic guanylate cylase activity in cell-free preparations of the rabbit renal cortex was increased 3- to 5-fold by catecholamines. The plasma membrane-bound enzyme was not activated, although hormone receptors were present. Stimulation was augmented by NaN3, which by itself had little effect on the soluble enzyme activity. With a partially purified enzyme, activity was enhanced by 0.1 muM 1-epinephrine and activated half-maximally by about 1 muM. In decreasing potency, epinephrine greater than isoproterenol greater than norepinephrine greater than dopamine greater than catechol. Phenylephrine and metanephrine did not stimulate. 1-Epinephrine-stimulation of the enzyme was reversed by dialysis and the deactivated enzyme was reactivatable by a second exposure to the catecholamine. Activation by catecholamines was not stereospecific. Epinephrine-stimulated guanylate cyclase activity in the crude cytosolic fraction was partially inhibited by alpha-adrenergic antagonists, but neither alpha- nor beta-blockers inhibited when the partially purified enzyme was used; thus, leaving open the question of a role for typical alpha- or beta-adrenergic mechanisms in this regulation of the soluble enzyme. Adrenochrome was the most potent activator of the partially purified guanylate cyclase, being approximately 10-times more effective than epinephrine. Epinephrine and adrenochrome activated in the presence of reducing agents, i.e., ascorbate, DTT and N2, although the enzyme in a more SH-reduced form and in an oxygen-deficient medium had a decreased sensitivity to both effectors. Epinephrine activated soluble guanylate cyclase in several tissues, including cerebrum, cerebellum, brain stem, lung, heart, liver, ductus deferens and colon. Although the precise mechanism by which low concentrations of catecholamines stimulated guanylate cyclase activity is unknown and the physiological significance of the activation remains to be established, these findings direct attention to an interesting interaction of catecholamines with the cytosolic enzyme system and stress the need for further studies.", "contents": "The stimulation by catecholamines of guanylate cyclase activity in a cell-free system. Cytosolic guanylate cylase activity in cell-free preparations of the rabbit renal cortex was increased 3- to 5-fold by catecholamines. The plasma membrane-bound enzyme was not activated, although hormone receptors were present. Stimulation was augmented by NaN3, which by itself had little effect on the soluble enzyme activity. With a partially purified enzyme, activity was enhanced by 0.1 muM 1-epinephrine and activated half-maximally by about 1 muM. In decreasing potency, epinephrine greater than isoproterenol greater than norepinephrine greater than dopamine greater than catechol. Phenylephrine and metanephrine did not stimulate. 1-Epinephrine-stimulation of the enzyme was reversed by dialysis and the deactivated enzyme was reactivatable by a second exposure to the catecholamine. Activation by catecholamines was not stereospecific. Epinephrine-stimulated guanylate cyclase activity in the crude cytosolic fraction was partially inhibited by alpha-adrenergic antagonists, but neither alpha- nor beta-blockers inhibited when the partially purified enzyme was used; thus, leaving open the question of a role for typical alpha- or beta-adrenergic mechanisms in this regulation of the soluble enzyme. Adrenochrome was the most potent activator of the partially purified guanylate cyclase, being approximately 10-times more effective than epinephrine. Epinephrine and adrenochrome activated in the presence of reducing agents, i.e., ascorbate, DTT and N2, although the enzyme in a more SH-reduced form and in an oxygen-deficient medium had a decreased sensitivity to both effectors. Epinephrine activated soluble guanylate cyclase in several tissues, including cerebrum, cerebellum, brain stem, lung, heart, liver, ductus deferens and colon. Although the precise mechanism by which low concentrations of catecholamines stimulated guanylate cyclase activity is unknown and the physiological significance of the activation remains to be established, these findings direct attention to an interesting interaction of catecholamines with the cytosolic enzyme system and stress the need for further studies."}
{"id": "PMID:26704", "title": "gamma-Glutamyl transpeptidase in lactating mammary secretory tissue of cow and rat.", "content": "Lactating cow and rat tissues were examined for gamma-glutamyl transpeptidase. The specificity of the enzyme for various amino acid acceptors was determined for mammary tissue. The relative specific activity of gamma-glutamyl transpeptidase was high in cow mammary tissue and lower in rat mammary tissue in relation to the activity in kidney of the respective mammals. However, activity per gram wet weight of mammary tissues appeared equivalent. gamma-Glutamyl transpeptidase activity towards specific amino acids agreed with the percent extractions of these amino acids by the mammary gland of the lactating cow in vivo. We believe this is the first evidence of a possible system of amino acid transport by mammary tissues.", "contents": "gamma-Glutamyl transpeptidase in lactating mammary secretory tissue of cow and rat. Lactating cow and rat tissues were examined for gamma-glutamyl transpeptidase. The specificity of the enzyme for various amino acid acceptors was determined for mammary tissue. The relative specific activity of gamma-glutamyl transpeptidase was high in cow mammary tissue and lower in rat mammary tissue in relation to the activity in kidney of the respective mammals. However, activity per gram wet weight of mammary tissues appeared equivalent. gamma-Glutamyl transpeptidase activity towards specific amino acids agreed with the percent extractions of these amino acids by the mammary gland of the lactating cow in vivo. We believe this is the first evidence of a possible system of amino acid transport by mammary tissues."}
{"id": "PMID:26707", "title": "Effect of endosulfan on drug metabolizing enzymes and lipid peroxidation in rat.", "content": "The influence of endosulfan, a chlorinated hydrocarbon insecticide, on rat hepatic drug metabolizing enzymes and lipid peroxidation has been explored in the present study. Total liver weight was significantly increased after endosulfan administration at both dose levels (2.5 and 5.0 mg/kg body weight) without affecting body weight or 9000 x g supernatant protein content. There was a marked increase in the activity of aminopyrine-N-demethylase, aniline hydroxylase, tyrosine amino-transferase and spontaneous lipid peroxidation. In all cases the increase was dose dependent.", "contents": "Effect of endosulfan on drug metabolizing enzymes and lipid peroxidation in rat. The influence of endosulfan, a chlorinated hydrocarbon insecticide, on rat hepatic drug metabolizing enzymes and lipid peroxidation has been explored in the present study. Total liver weight was significantly increased after endosulfan administration at both dose levels (2.5 and 5.0 mg/kg body weight) without affecting body weight or 9000 x g supernatant protein content. There was a marked increase in the activity of aminopyrine-N-demethylase, aniline hydroxylase, tyrosine amino-transferase and spontaneous lipid peroxidation. In all cases the increase was dose dependent."}
{"id": "PMID:26709", "title": "Onchocerca sweetae (Nematoda: Filarioidea): notes on the intermediate host.", "content": "Microfilariae of Onchocerca sweetae are broadly distributed in the superficial layers of the dermis of the water buffalo (Bubalus bubalis). A total of 2855 insects representing 20 species were collected from O. sweetae-infected bait buffaloes. Only one species, Culicoides sp. \"M\", ingested microfilariae from buffalo skin. Larval development of O. sweetae was observed in the thorax of this species. Atotal of 829 insects, representing 7 species and including 749 parous Culicoides spp. were collected from light and Manitoba traps. Developing filarioid larvae were observed only in Culicoides sp. \"M\". It is concluded that Culicoides sp. \"M\" is a natural intermediate host of O. sweetae in the Northern Territory of Australia.", "contents": "Onchocerca sweetae (Nematoda: Filarioidea): notes on the intermediate host. Microfilariae of Onchocerca sweetae are broadly distributed in the superficial layers of the dermis of the water buffalo (Bubalus bubalis). A total of 2855 insects representing 20 species were collected from O. sweetae-infected bait buffaloes. Only one species, Culicoides sp. \"M\", ingested microfilariae from buffalo skin. Larval development of O. sweetae was observed in the thorax of this species. Atotal of 829 insects, representing 7 species and including 749 parous Culicoides spp. were collected from light and Manitoba traps. Developing filarioid larvae were observed only in Culicoides sp. \"M\". It is concluded that Culicoides sp. \"M\" is a natural intermediate host of O. sweetae in the Northern Territory of Australia."}
{"id": "PMID:26717", "title": "Ultrastructural localization of alkaline phosphatases in rat incisor odontoblasts.", "content": "The localization of alkaline phosphatases in dentinogenically active rat incisor odontoblasts was studied by means of subcellular fractionation and electron microscopical histochemistry. Subcellular fractionation revealed the predominant phosphatase activity to be present in the microsome fraction and to a lesser extent in the mitochondrial fraction. Adenosine triphosphate degrading enzyme activity was determined in the presence or absence of (+/-)-6(m-bromophenyl)-5, 6-dihydroimidazo(le) (2,1-b) thiazole oxalate (R 8231). Before the histochemical study, the effects on phosphatase activities by aldehyde fixation were studied by biochemical assay. A method of fixation for optimal preservation of phosphatase activity is presented. Phosphatase electron microscopic histochemistry was performed by using ATP as a substrate and with or without addition of the inhibitor R 82319 Precipitates were seen in the membranes of vesicles present in the odontoblast process and the Golgi region. When there were signs of insufficient fixation, precipitates were also seen in the outer membranes of mitochondria. No phosphatase activity was seen in the cell membrane. ATP degrading enzyme activities mediated by nonspecific alkaline phosphatase (APase) and Ca2+ -adenosine triphosphatase thus have the same morphological localization. This close association is consistent with earlier biochemical studies.", "contents": "Ultrastructural localization of alkaline phosphatases in rat incisor odontoblasts. The localization of alkaline phosphatases in dentinogenically active rat incisor odontoblasts was studied by means of subcellular fractionation and electron microscopical histochemistry. Subcellular fractionation revealed the predominant phosphatase activity to be present in the microsome fraction and to a lesser extent in the mitochondrial fraction. Adenosine triphosphate degrading enzyme activity was determined in the presence or absence of (+/-)-6(m-bromophenyl)-5, 6-dihydroimidazo(le) (2,1-b) thiazole oxalate (R 8231). Before the histochemical study, the effects on phosphatase activities by aldehyde fixation were studied by biochemical assay. A method of fixation for optimal preservation of phosphatase activity is presented. Phosphatase electron microscopic histochemistry was performed by using ATP as a substrate and with or without addition of the inhibitor R 82319 Precipitates were seen in the membranes of vesicles present in the odontoblast process and the Golgi region. When there were signs of insufficient fixation, precipitates were also seen in the outer membranes of mitochondria. No phosphatase activity was seen in the cell membrane. ATP degrading enzyme activities mediated by nonspecific alkaline phosphatase (APase) and Ca2+ -adenosine triphosphatase thus have the same morphological localization. This close association is consistent with earlier biochemical studies."}
{"id": "PMID:26718", "title": "Deposition of IgM and complement at the dermoepidermal junction in acute and chronic cutaneous graft-vs-host disease in man.", "content": "The presence of cutaneous immunoglobulin and complement was investigated in 88 patients with and without graft-vs-host disease (GVHD) after transplantation of bone marrow from HLA identical siblings for the treatment of acute leukemia or aplastic anemia. For comparison, skin biopsies from the patients obtained before transplantation, from 58 healthy individuals (mostly marrow donors) and from four syngeneic marrow recipients were studied. A direct immunfluorescent staining technique was used. Dermo-epidermal IgM deposits were found in 11% of healthy individuals and patients before grafting but were present in 86% of patients with chronic and 39% of patients with acute GVHD. Patients with allogeneic grafts who never had GVHD or who had recovered from it and patients with syngeneic grafts showed findings not different from those in healthy individuals. Findings similar to those with IgM, although less striking, were made for C3, i.e., patients who had chronic or acute GVHD had a high incidence and intensity of C3 deposits at the dermo-epidermal junction. This observation raises the possibility that humoral immunity is involved in the development of GVHD.", "contents": "Deposition of IgM and complement at the dermoepidermal junction in acute and chronic cutaneous graft-vs-host disease in man. The presence of cutaneous immunoglobulin and complement was investigated in 88 patients with and without graft-vs-host disease (GVHD) after transplantation of bone marrow from HLA identical siblings for the treatment of acute leukemia or aplastic anemia. For comparison, skin biopsies from the patients obtained before transplantation, from 58 healthy individuals (mostly marrow donors) and from four syngeneic marrow recipients were studied. A direct immunfluorescent staining technique was used. Dermo-epidermal IgM deposits were found in 11% of healthy individuals and patients before grafting but were present in 86% of patients with chronic and 39% of patients with acute GVHD. Patients with allogeneic grafts who never had GVHD or who had recovered from it and patients with syngeneic grafts showed findings not different from those in healthy individuals. Findings similar to those with IgM, although less striking, were made for C3, i.e., patients who had chronic or acute GVHD had a high incidence and intensity of C3 deposits at the dermo-epidermal junction. This observation raises the possibility that humoral immunity is involved in the development of GVHD."}
{"id": "PMID:26719", "title": "Pharmacologic control of the hormonally modulated immune response. III. Prolongation of allogeneic skin graft rejection and prevention of runt disease by a combination of drugs acting on neuroendocrine functions.", "content": "A recently developed pharmacologic means for suppressing acquired immunity by drugs acting on neuroendocrine regulation has been applied to transplantation immune reactions. A number of drugs have been tested singly and in combination for their capacity to suppress the immune response of mice grafted with allogeneic skin. Another model involved newborn F1 hybrid recipients inoculated with spleen cells from donors of parental strains that had been made specifically \"unresponsive\" by drug and alloantigen treatment. These procedures led to the identification of a combination of four drugs that induced a remarkable delay in allograft rejection and a prolonged unresponsiveness to alloantigens. This combination of drugs also abrogated the graft-vs-host-runting syndrome in newborn hybrid recipients.", "contents": "Pharmacologic control of the hormonally modulated immune response. III. Prolongation of allogeneic skin graft rejection and prevention of runt disease by a combination of drugs acting on neuroendocrine functions. A recently developed pharmacologic means for suppressing acquired immunity by drugs acting on neuroendocrine regulation has been applied to transplantation immune reactions. A number of drugs have been tested singly and in combination for their capacity to suppress the immune response of mice grafted with allogeneic skin. Another model involved newborn F1 hybrid recipients inoculated with spleen cells from donors of parental strains that had been made specifically \"unresponsive\" by drug and alloantigen treatment. These procedures led to the identification of a combination of four drugs that induced a remarkable delay in allograft rejection and a prolonged unresponsiveness to alloantigens. This combination of drugs also abrogated the graft-vs-host-runting syndrome in newborn hybrid recipients."}
{"id": "PMID:26723", "title": "Antibody response to capsular polysaccharide vaccine of Streptococcus pneumoniae in patients with nephrotic syndrome.", "content": "Twenty-three normal subjects and 19 patients with nephrotic syndrome were vaccinated with tridecavalent pneumococcal capsular polysaccharide vaccine of Streptococcus pneumoniae. The antibody response of the nephrotic patients to pneumococcal capsular antigens was equal to that of the control subjects. These findings indicate that patients with nephrotic syndrome, despite hypogammaglobulinemia, can mount an adequate antibody response to pneumococcal polysaccharides and that there is no evidence of suppressor thymus-derived (T) cells of dysfunctioning bone marrow-derived (B) cells in these patients.", "contents": "Antibody response to capsular polysaccharide vaccine of Streptococcus pneumoniae in patients with nephrotic syndrome. Twenty-three normal subjects and 19 patients with nephrotic syndrome were vaccinated with tridecavalent pneumococcal capsular polysaccharide vaccine of Streptococcus pneumoniae. The antibody response of the nephrotic patients to pneumococcal capsular antigens was equal to that of the control subjects. These findings indicate that patients with nephrotic syndrome, despite hypogammaglobulinemia, can mount an adequate antibody response to pneumococcal polysaccharides and that there is no evidence of suppressor thymus-derived (T) cells of dysfunctioning bone marrow-derived (B) cells in these patients."}
{"id": "PMID:26727", "title": "Vulnerability of keto bile acids to alkaline hydrolysis.", "content": "Rigorous alkaline hydrolysis of the two primary (cholic and chenodeoxycholic) and of the two preponderant secondary (deoxycholic and lithocholic) bile acids found in bile led to excellent recoveries. Such was not the case with 11 different keto bile acid standards. Recoveries for a number of standards were unacceptably low and a variety of artefactural products were tentatively identified by gas-liquid chromatography. Keto bile acids bearing a keto gropu on C-3 were particularly vulnerable. In view of thee findings, quantitative and qualitative data reported on biological specimens submitted to saponification in ethanol, methanol, or even in water are of questionable significance.", "contents": "Vulnerability of keto bile acids to alkaline hydrolysis. Rigorous alkaline hydrolysis of the two primary (cholic and chenodeoxycholic) and of the two preponderant secondary (deoxycholic and lithocholic) bile acids found in bile led to excellent recoveries. Such was not the case with 11 different keto bile acid standards. Recoveries for a number of standards were unacceptably low and a variety of artefactural products were tentatively identified by gas-liquid chromatography. Keto bile acids bearing a keto gropu on C-3 were particularly vulnerable. In view of thee findings, quantitative and qualitative data reported on biological specimens submitted to saponification in ethanol, methanol, or even in water are of questionable significance."}
{"id": "PMID:26728", "title": "Binding of [3H]ouabain to split frog skin: the role of the Na,K-ATPase in the generation of short circuit current.", "content": "The binding of [3H]ouabain to the serosal side was studied in a chambered preparation of frog skin, free of connective tissue, while the short circuit (Isc) was concurrently monitored. Both ouabain binding and Isc inhibition proceeded as hyperbolic functions of time. A plot of the number of ouabain molecules bound vs. the corresponding values of Isc inhibition (percent) yielded a straight line, yet showed that one-third of the binding occurred before any inhibition of Isc. Upon separation of the skins into two groups based upon initial Isc(Isci)--high, greater than 20 microamperemeter/cm2 and low, less than 10 microamperemeter/cm2, we observed two distinct populations. The high Isci skins bound very little ouabain before inhibition of Isc whereas low Isci skins bound one-half of the total number of sites before exhibiting any inhibition of Isc. These observations strongly suggest that (a) the Na,K-ATPase is directly involved in the generation of Isc, and (b) at low Isc, inhibition of some pumps by ouabain causes a \"recruitment\" of other pumps to increase their turnover rate and maintain Isc relatively unaffected. In addition, the binding of ouabain also displayed various characteristics that were consistent with known properties of the Na,K-ATPase: (a) increased intracellular K/Na concentrations, whether achieved through the addition of amiloride or removal of Na from the outside medium, led to a significant decrease in ouabain binding rate relative to paired controls; and (b) ouabain binding, either with normal or decreased intracellular Na, was significantly reduced in the presence of elevated K in the serosal bathing medium. Finally, the number of ouabain molecules bound to the frog skins was not correlated with their initial Isc values, indicating that the spontaneous skin-to-skin variation in Isc was not related to the number of functional pump sites but, rather, to their turnover rate.", "contents": "Binding of [3H]ouabain to split frog skin: the role of the Na,K-ATPase in the generation of short circuit current. The binding of [3H]ouabain to the serosal side was studied in a chambered preparation of frog skin, free of connective tissue, while the short circuit (Isc) was concurrently monitored. Both ouabain binding and Isc inhibition proceeded as hyperbolic functions of time. A plot of the number of ouabain molecules bound vs. the corresponding values of Isc inhibition (percent) yielded a straight line, yet showed that one-third of the binding occurred before any inhibition of Isc. Upon separation of the skins into two groups based upon initial Isc(Isci)--high, greater than 20 microamperemeter/cm2 and low, less than 10 microamperemeter/cm2, we observed two distinct populations. The high Isci skins bound very little ouabain before inhibition of Isc whereas low Isci skins bound one-half of the total number of sites before exhibiting any inhibition of Isc. These observations strongly suggest that (a) the Na,K-ATPase is directly involved in the generation of Isc, and (b) at low Isc, inhibition of some pumps by ouabain causes a \"recruitment\" of other pumps to increase their turnover rate and maintain Isc relatively unaffected. In addition, the binding of ouabain also displayed various characteristics that were consistent with known properties of the Na,K-ATPase: (a) increased intracellular K/Na concentrations, whether achieved through the addition of amiloride or removal of Na from the outside medium, led to a significant decrease in ouabain binding rate relative to paired controls; and (b) ouabain binding, either with normal or decreased intracellular Na, was significantly reduced in the presence of elevated K in the serosal bathing medium. Finally, the number of ouabain molecules bound to the frog skins was not correlated with their initial Isc values, indicating that the spontaneous skin-to-skin variation in Isc was not related to the number of functional pump sites but, rather, to their turnover rate."}
{"id": "PMID:26730", "title": "Preferences by deer mice for solutions of sugars, salts, and acids in Richter-type drinking tests.", "content": "Deer mice (Peromyscus maniculatus) were tested for taste preferences in 48-hour, Richter-type drinking tests (sapid solution versus distilled water). The Ss, which were seven male and seven female wild adults, were individually housed within an environmental chamber. Test solutions were concentrations of five sugars and three salts (.005 M to 1.0 M) and of two acids (4.0 pH to 1.5 pH). The molar range was too limited to identify the most preferred concentration of glucose, but peak preferences for the other common sugars fell within the range. Preference was shown for hypotonic NaCl concentrations, but other salts and both acids were nonpreferred in all tests. Comparisons were made between these findings and results from Richter-type tests with other murine rodents.", "contents": "Preferences by deer mice for solutions of sugars, salts, and acids in Richter-type drinking tests. Deer mice (Peromyscus maniculatus) were tested for taste preferences in 48-hour, Richter-type drinking tests (sapid solution versus distilled water). The Ss, which were seven male and seven female wild adults, were individually housed within an environmental chamber. Test solutions were concentrations of five sugars and three salts (.005 M to 1.0 M) and of two acids (4.0 pH to 1.5 pH). The molar range was too limited to identify the most preferred concentration of glucose, but peak preferences for the other common sugars fell within the range. Preference was shown for hypotonic NaCl concentrations, but other salts and both acids were nonpreferred in all tests. Comparisons were made between these findings and results from Richter-type tests with other murine rodents."}
{"id": "PMID:26734", "title": "Effect on the Cushing response of different rates of expansion of a supratentorial mass.", "content": "The effects on the three components (respiration, blood pressure, and heart rate) of the Cushing response (CR) were studied in cats by the continuous expansion of a supratentorial balloon. The rate of expansion was varied over the range of 0.006 to 0.6 ml/min, during whic systemic arterial pressure, heart rate, respiratory rate, and blood gases were monitored. For the different rates the time the CR took to develop, and the balloon volume required for that development were measured. The final volume (\"critical volume\") for eliciting the CR was more or less constant over the full range of rates of infusion (balloon expansion), a fact that supports that Monro-Kellie doctrine. This constancy of critical volume (CCV) gives rise to a highly statistically significant relationship between the rate of infusion and the latency to the production of the CR, and it is described by a power curve. Thus the development of cerebral dysfunction under these experimental conditions is independent of the rate of expansion and only dependent upon this critical volume. Exceptions to this concept of a critical volume, at the extreme of rates of expansion of lesions in patients, are predicted.", "contents": "Effect on the Cushing response of different rates of expansion of a supratentorial mass. The effects on the three components (respiration, blood pressure, and heart rate) of the Cushing response (CR) were studied in cats by the continuous expansion of a supratentorial balloon. The rate of expansion was varied over the range of 0.006 to 0.6 ml/min, during whic systemic arterial pressure, heart rate, respiratory rate, and blood gases were monitored. For the different rates the time the CR took to develop, and the balloon volume required for that development were measured. The final volume (\"critical volume\") for eliciting the CR was more or less constant over the full range of rates of infusion (balloon expansion), a fact that supports that Monro-Kellie doctrine. This constancy of critical volume (CCV) gives rise to a highly statistically significant relationship between the rate of infusion and the latency to the production of the CR, and it is described by a power curve. Thus the development of cerebral dysfunction under these experimental conditions is independent of the rate of expansion and only dependent upon this critical volume. Exceptions to this concept of a critical volume, at the extreme of rates of expansion of lesions in patients, are predicted."}
{"id": "PMID:26735", "title": "Bacterial etiology of otitis media during the first six weeks of life.", "content": "Tympanocentesis was performed on 70 infants who had otitis media during the first six weeks of life. The bacteria isolated from their middle-ear effusions were Streptococcus pneumoniae (13 patients), Neisseria catarrhalis (11 patients), Hemophilus influenzae (ten patients), Enterobacteriaceae (four patients), Staphylococcus aureus (four patients), streptococci (groups A and B) (three patients), and Pseudomonas aeruginosa (two patients). Thirty patients (42.9%) had middle-ear effusions which did not contain pathogenic bacteria. Twenty-seven infants were followed for at least 12 months and 12 (44.4%) of these infants had six or more episodes of otitis media during the observation period. Further studies will be needed to establish the significance of middle-ear disease at this age and the role of therapy in improving its outcome.", "contents": "Bacterial etiology of otitis media during the first six weeks of life. Tympanocentesis was performed on 70 infants who had otitis media during the first six weeks of life. The bacteria isolated from their middle-ear effusions were Streptococcus pneumoniae (13 patients), Neisseria catarrhalis (11 patients), Hemophilus influenzae (ten patients), Enterobacteriaceae (four patients), Staphylococcus aureus (four patients), streptococci (groups A and B) (three patients), and Pseudomonas aeruginosa (two patients). Thirty patients (42.9%) had middle-ear effusions which did not contain pathogenic bacteria. Twenty-seven infants were followed for at least 12 months and 12 (44.4%) of these infants had six or more episodes of otitis media during the observation period. Further studies will be needed to establish the significance of middle-ear disease at this age and the role of therapy in improving its outcome."}
{"id": "PMID:26736", "title": "In vivo and in vitro excystation of Zygocotyle lunata (Trematoda) metacercariae and histochemical observations on the cyst.", "content": "Encysted metacercariae of Zygocotyle lunata (Trematoda) excyst within 2 hr postexposure in the lower ileum of the domestic chick. Optimal in vitro excystation of this species occurs following pretreatment of the cyst for 15 min in 1% acidified pepsin, treatment in 0.02 M sodium dithionite (a reductant) for 1 to 2 min and then 2 hr treatment in an excystation medium containing 1% sodium glycocholate plus 1% trypsin in Earle's BSS adjusted to pH 8.8 with tris and maintained at 41 C. The cyst of this species is a dome-shaped hemisphere containing an inner and outer wall. The outer wall contains mainly acid mucopolysaccharides, whereas the inner wall is mainly proteinaceous. The cyst contains a ventral lid which only was visualized during excystation.", "contents": "In vivo and in vitro excystation of Zygocotyle lunata (Trematoda) metacercariae and histochemical observations on the cyst. Encysted metacercariae of Zygocotyle lunata (Trematoda) excyst within 2 hr postexposure in the lower ileum of the domestic chick. Optimal in vitro excystation of this species occurs following pretreatment of the cyst for 15 min in 1% acidified pepsin, treatment in 0.02 M sodium dithionite (a reductant) for 1 to 2 min and then 2 hr treatment in an excystation medium containing 1% sodium glycocholate plus 1% trypsin in Earle's BSS adjusted to pH 8.8 with tris and maintained at 41 C. The cyst of this species is a dome-shaped hemisphere containing an inner and outer wall. The outer wall contains mainly acid mucopolysaccharides, whereas the inner wall is mainly proteinaceous. The cyst contains a ventral lid which only was visualized during excystation."}
{"id": "PMID:26737", "title": "Studies with Brugia pahangi 17. The anthelmintic effects of diethylcarbamazine.", "content": "Diethylcarbamazine (DEC) was active in vitro against infective larvae and microfilariae of Brugia pahangi but only at high concentrations. When fed to mosquitoes which were infected with B. pahangi it had little or no activity. In jirds it was inactive against B. pahangi microfilariae and adults when administered at 300 mg/kg for 5 days either by the intraperitoneal or oral route. In cats given 25 or 50 mg DEC/kg intraperitoneally on 3 or 5 occasions it was not microfilaricidal, but most of the adult worms died within 30 days of the end of treatment. Although most microfilariae disappeared from the blood of cats immediately (i.e., within an hour) after treatment, they reappeared within a few hours in the same numbers. Microfilarial levels were reduced after treatment but there was no precipitate decline as occurs in human B. malayi patients.", "contents": "Studies with Brugia pahangi 17. The anthelmintic effects of diethylcarbamazine. Diethylcarbamazine (DEC) was active in vitro against infective larvae and microfilariae of Brugia pahangi but only at high concentrations. When fed to mosquitoes which were infected with B. pahangi it had little or no activity. In jirds it was inactive against B. pahangi microfilariae and adults when administered at 300 mg/kg for 5 days either by the intraperitoneal or oral route. In cats given 25 or 50 mg DEC/kg intraperitoneally on 3 or 5 occasions it was not microfilaricidal, but most of the adult worms died within 30 days of the end of treatment. Although most microfilariae disappeared from the blood of cats immediately (i.e., within an hour) after treatment, they reappeared within a few hours in the same numbers. Microfilarial levels were reduced after treatment but there was no precipitate decline as occurs in human B. malayi patients."}
{"id": "PMID:26739", "title": "Tryptamine-induced drug effects insensitive to serotoninergic antagonists: evidence of specific tryptaminergic receptor stimulation?", "content": "The drug effects of tryptamine and 5-hydroxytryptopham (5-HTP) in the rabbit were compared following monoamine oxidase inhibition and various drug pretreatments. Both agents evoked hyperthermia and behavioural excitation; tryptamine but not 5-HTP also produced forepaw clonic activity. Serotoninergic receptor blockers abolished the effects of 5-HTP but only weakly influenced tryptamine responses. Both tryptamine and 5-HTP effects were potentiated by fluoxetine. Methergoline, a putative tryptaminergic receptor blocker, antagonized tryptamine-induced hyperthermia and forepaw clonus but did not influence 5-HTP responses. It is postulated that while 5-HTP produces its effects through a serotoninergic mechanism, some of the responses to tryptamine result from activation of a specific tryptamine-sensitive mechanism.", "contents": "Tryptamine-induced drug effects insensitive to serotoninergic antagonists: evidence of specific tryptaminergic receptor stimulation? The drug effects of tryptamine and 5-hydroxytryptopham (5-HTP) in the rabbit were compared following monoamine oxidase inhibition and various drug pretreatments. Both agents evoked hyperthermia and behavioural excitation; tryptamine but not 5-HTP also produced forepaw clonic activity. Serotoninergic receptor blockers abolished the effects of 5-HTP but only weakly influenced tryptamine responses. Both tryptamine and 5-HTP effects were potentiated by fluoxetine. Methergoline, a putative tryptaminergic receptor blocker, antagonized tryptamine-induced hyperthermia and forepaw clonus but did not influence 5-HTP responses. It is postulated that while 5-HTP produces its effects through a serotoninergic mechanism, some of the responses to tryptamine result from activation of a specific tryptamine-sensitive mechanism."}
{"id": "PMID:26740", "title": "Rectal absorption of homatropine [14C]methylbromide in the rat.", "content": "Homatropine[14C]methylbromide (HMB-14C) was administered to rats by intramuscular injection, oral gavage and rectal suppository. Plasma concentration of 14C were measured over the subsequent 12 h. Peak plasma concentrations were higher and achieved more rapidly after rectal administration than by the other routes whether HMB-14C was administered in a water-soluble suppository base or in aqueous solution. Twelve h after the suppositories were inserted and retained 28% of the 14C had been excreted in the urine while 56% remained in the large intestine. Unlabelled HMB, given in rectal suppositories to anaesthetized rats, caused prompt blockade of the effects of vagal stimulation on pulse rate and of intravenous acetylcholine on blood pressure. These results confirm the rapid rectal absorption of the drug.", "contents": "Rectal absorption of homatropine [14C]methylbromide in the rat. Homatropine[14C]methylbromide (HMB-14C) was administered to rats by intramuscular injection, oral gavage and rectal suppository. Plasma concentration of 14C were measured over the subsequent 12 h. Peak plasma concentrations were higher and achieved more rapidly after rectal administration than by the other routes whether HMB-14C was administered in a water-soluble suppository base or in aqueous solution. Twelve h after the suppositories were inserted and retained 28% of the 14C had been excreted in the urine while 56% remained in the large intestine. Unlabelled HMB, given in rectal suppositories to anaesthetized rats, caused prompt blockade of the effects of vagal stimulation on pulse rate and of intravenous acetylcholine on blood pressure. These results confirm the rapid rectal absorption of the drug."}
{"id": "PMID:26741", "title": "The mechanism of the hypothermic effect of amantadine in rats and mice.", "content": "Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors.", "contents": "The mechanism of the hypothermic effect of amantadine in rats and mice. Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors."}
{"id": "PMID:26742", "title": "Some pharmacological actions of acetylsecohemicholinium.", "content": "The effects of the acetylated derivative of HC-3 (acetylsecohemicholinium; AcHC-3) have been studied at cholinergic nerve terminals and compared with the effects of the parent compound. AcHC-3 blocked neuromuscular transmission in nerve-muscle preparations; it was shown to be less effective than HC-3 in producing a pre-junctional block in the rat diaphragm but was more effective than HC-3 in eliciting a post-junctional blocking effect in the chick biventer muscle. On the frog rectus abdominis muscle AcHC-3 caused a substantial potentiation of the contractures elicited by acetylcholine but did not by itself cause a contracture of the muscle. AcHC-3 inhibited the synthesis of acetylcholine by cholinergic nerve ending particles and inhibited the uptake of [14C]choline into brain synaptosomal fractions to a similar extent to HC-3. AcHC-3 was shown to be a substrate for cholinesterase enzymes although the rate of hydrolysis was much less than the rate of hydrolysis of acetylcholine. It is concluded that AcHC-3 is effective in inhibiting cholinergic transmission and this action is exerted by the open chain (seco) compound and is not due to the hydrolysis of the AcHC-3 by cholinesterases to form the active HC-3 molecule.", "contents": "Some pharmacological actions of acetylsecohemicholinium. The effects of the acetylated derivative of HC-3 (acetylsecohemicholinium; AcHC-3) have been studied at cholinergic nerve terminals and compared with the effects of the parent compound. AcHC-3 blocked neuromuscular transmission in nerve-muscle preparations; it was shown to be less effective than HC-3 in producing a pre-junctional block in the rat diaphragm but was more effective than HC-3 in eliciting a post-junctional blocking effect in the chick biventer muscle. On the frog rectus abdominis muscle AcHC-3 caused a substantial potentiation of the contractures elicited by acetylcholine but did not by itself cause a contracture of the muscle. AcHC-3 inhibited the synthesis of acetylcholine by cholinergic nerve ending particles and inhibited the uptake of [14C]choline into brain synaptosomal fractions to a similar extent to HC-3. AcHC-3 was shown to be a substrate for cholinesterase enzymes although the rate of hydrolysis was much less than the rate of hydrolysis of acetylcholine. It is concluded that AcHC-3 is effective in inhibiting cholinergic transmission and this action is exerted by the open chain (seco) compound and is not due to the hydrolysis of the AcHC-3 by cholinesterases to form the active HC-3 molecule."}
{"id": "PMID:26743", "title": "A mammalian muscle with the pharmacological characteristics of slow tonic muscle.", "content": "The guinea-pig isolated cremaster muscle gave tetrodotoxin-resistant dose-related contractures with acetylcholine, carbachol and the depolarizing neuromuscular blocking agents. The dose-response curve to suxamethonium in tetrodotoxin 2 X 10(-7)M could be shifted to the right with tubocurarine 10(-6)M. KCl, 0.1M, produced slow sustained contractures of the muscle. With the cremaster nerve-muscle preparation tetanic contractions at 20 Hz were maintained over several minutes. Tetrodotoxin eliminated the twitch response to single shock nerve stimulation but not the sustained increase in tension produced by suxamethonium. The results suggest either that there is a component of slow tonic muscle in the guinea-pig cremaster or that the cremaster consists of a type of focally innervated muscle which has pharmacological responses qualitatively different from those of most focally innervated muscles so far described.", "contents": "A mammalian muscle with the pharmacological characteristics of slow tonic muscle. The guinea-pig isolated cremaster muscle gave tetrodotoxin-resistant dose-related contractures with acetylcholine, carbachol and the depolarizing neuromuscular blocking agents. The dose-response curve to suxamethonium in tetrodotoxin 2 X 10(-7)M could be shifted to the right with tubocurarine 10(-6)M. KCl, 0.1M, produced slow sustained contractures of the muscle. With the cremaster nerve-muscle preparation tetanic contractions at 20 Hz were maintained over several minutes. Tetrodotoxin eliminated the twitch response to single shock nerve stimulation but not the sustained increase in tension produced by suxamethonium. The results suggest either that there is a component of slow tonic muscle in the guinea-pig cremaster or that the cremaster consists of a type of focally innervated muscle which has pharmacological responses qualitatively different from those of most focally innervated muscles so far described."}
{"id": "PMID:26744", "title": "Effect of carbenoxolone on lipolysis in rat adipose tissue.", "content": "Carbenoxolone slightly but significantly decreased the release of FFA from rat epididymal fat pads. The antilipolytic action of carbenoxolone was not blocked by 10(-3)M 3-isobutyl-1-methylxanthine, a potent inhibitor of phosphodiesterase. The findings suggest that carbenoxolone exerts its antilipolytic activity by acting on adenylate cyclase, thereby decreasing cyclic AMP concentrations and the activity of the hormone-sensitive lipase in adipose tissue.", "contents": "Effect of carbenoxolone on lipolysis in rat adipose tissue. Carbenoxolone slightly but significantly decreased the release of FFA from rat epididymal fat pads. The antilipolytic action of carbenoxolone was not blocked by 10(-3)M 3-isobutyl-1-methylxanthine, a potent inhibitor of phosphodiesterase. The findings suggest that carbenoxolone exerts its antilipolytic activity by acting on adenylate cyclase, thereby decreasing cyclic AMP concentrations and the activity of the hormone-sensitive lipase in adipose tissue."}
{"id": "PMID:26745", "title": "The inhibition by clorgyline of 5-hydroxytryptamine deamination by the rat liver.", "content": "The inhibition of the monoamine oxidase activity in the rat liver by the substrate selective inhibitor clorgyline has been investigated with 5-hydroxytryptamine as substrate. The results obtained are consistent with a theoretical model whereby the inhibition of enzyme activity by clorgyline follows a reversible association phase leading to an irreversible 'suicide' reaction. The relative concentrations of enzyme and inhibitor are of the same order, and can account both for the failure of the reaction to go to completion, and for the differences in the apparent sensitivity of enzyme preparations to inhibition by clorgyline. The possible value of this type of inhibition as a means of assay for monoamine oxidase active centres is discussed.", "contents": "The inhibition by clorgyline of 5-hydroxytryptamine deamination by the rat liver. The inhibition of the monoamine oxidase activity in the rat liver by the substrate selective inhibitor clorgyline has been investigated with 5-hydroxytryptamine as substrate. The results obtained are consistent with a theoretical model whereby the inhibition of enzyme activity by clorgyline follows a reversible association phase leading to an irreversible 'suicide' reaction. The relative concentrations of enzyme and inhibitor are of the same order, and can account both for the failure of the reaction to go to completion, and for the differences in the apparent sensitivity of enzyme preparations to inhibition by clorgyline. The possible value of this type of inhibition as a means of assay for monoamine oxidase active centres is discussed."}
{"id": "PMID:26761", "title": "Interaction of cortisol-21-palmitate with liposomes examined by differential scanning calorimetry.", "content": "Liposomes have been suggested as carriers for corticosteroids in the local treatment of arthritis by intra-articular injection. The long chain 21-esters of cortisol such as the palmitate or octanoate are taken up and retained by liposomes in higher concentration than cortisol itself. Differential scanning calorimetry has been used to show that the cortisol ester is anchored in the liposome phospholipid bilayer by the acyl side chain. In addition, the limiting concentration of cortisol-21-palmitate which can be incorporated into dipalmitolyl phosphatidylcholine liposomes has been measured by observing changes in the DSC spectrum at different steroid concentrations. Steroid in excess of this concentration limit forms a separate phase which can be identified by nuclear magnetic resonance. For optimum effect, the treatment of arthritis with liposomes must be carried out with liposomes containing steroid below the limiting concentration.", "contents": "Interaction of cortisol-21-palmitate with liposomes examined by differential scanning calorimetry. Liposomes have been suggested as carriers for corticosteroids in the local treatment of arthritis by intra-articular injection. The long chain 21-esters of cortisol such as the palmitate or octanoate are taken up and retained by liposomes in higher concentration than cortisol itself. Differential scanning calorimetry has been used to show that the cortisol ester is anchored in the liposome phospholipid bilayer by the acyl side chain. In addition, the limiting concentration of cortisol-21-palmitate which can be incorporated into dipalmitolyl phosphatidylcholine liposomes has been measured by observing changes in the DSC spectrum at different steroid concentrations. Steroid in excess of this concentration limit forms a separate phase which can be identified by nuclear magnetic resonance. For optimum effect, the treatment of arthritis with liposomes must be carried out with liposomes containing steroid below the limiting concentration."}
{"id": "PMID:26762", "title": "The measurement of the adhesion of film coatings to tablet surfaces: the effect of tablet porosity, surface roughness and film thickness.", "content": "The effect of tablet porosity, surface roughness and film thickness on the adhesion of hydroxypropyl methyl cellulose films to placebo tablet substrates have been studied using a specially designed tensile tester (Fisher & Rowe, 4976). There were direct relations between measured adhesion and tablet porosity and also surface roughness and tablet porosity. The effect of film thickness on the measured adhesion is complex with an initial decrease with thicknesses up to 35 micron and then a gradual increase with thicknesses up to 140 micron dut to differences in the strees distribution within the film during testing. A knowledge of these effects is necessary if results from various sources are to be compared. The findings illustrate the potential capability of the extrapolation of measured adhesion results to zero porosity and zero thickness values in order to obtain a measure of the true or intrinsic adhesion at any film/tablet interface without the confusing elements of tablet porosity, surface roughness and residual stresses in the film.", "contents": "The measurement of the adhesion of film coatings to tablet surfaces: the effect of tablet porosity, surface roughness and film thickness. The effect of tablet porosity, surface roughness and film thickness on the adhesion of hydroxypropyl methyl cellulose films to placebo tablet substrates have been studied using a specially designed tensile tester (Fisher & Rowe, 4976). There were direct relations between measured adhesion and tablet porosity and also surface roughness and tablet porosity. The effect of film thickness on the measured adhesion is complex with an initial decrease with thicknesses up to 35 micron and then a gradual increase with thicknesses up to 140 micron dut to differences in the strees distribution within the film during testing. A knowledge of these effects is necessary if results from various sources are to be compared. The findings illustrate the potential capability of the extrapolation of measured adhesion results to zero porosity and zero thickness values in order to obtain a measure of the true or intrinsic adhesion at any film/tablet interface without the confusing elements of tablet porosity, surface roughness and residual stresses in the film."}
{"id": "PMID:26763", "title": "On methods of expressing dissolution rate data.", "content": "The value of the Weibull, logarithmic-logistic, and logarithmic-normal plots in expressing dissolution rate data is considered for the combinations of zero and first-order release with sink and non-sink conditions, and for actual dissolution rate data of diazepam from tablets in a medium of pH2.", "contents": "On methods of expressing dissolution rate data. The value of the Weibull, logarithmic-logistic, and logarithmic-normal plots in expressing dissolution rate data is considered for the combinations of zero and first-order release with sink and non-sink conditions, and for actual dissolution rate data of diazepam from tablets in a medium of pH2."}
{"id": "PMID:26765", "title": "Correlation of physicochemical properties with absorption and metabolism of some tricyclic drugs.", "content": "Octanol and dodecane partition coefficients, surface activity and adsorbability to activated charcoal were determined for six tricyclic psychotropic drugs with N-dimethylalkyl side chains. Surface activity correlated well with the partition coefficients, and all drugs obeyed the Langmuir adsorption isotherm. A correlation between the reciprocal of the death time of gold fish exposed to drugs and partition coefficients was observed. The extent to which the drugs were N-demethylated as measured by formaldehyde formed in rat liver homogenate incubations correlated with their adsorbability to activated charcoal but not with their ability to inhibit aniline-p-hydroxylase, nor was there a linear correspondence between N-DEMETHYLATION AND DRUG LIPOPHILICITY AS INDICATed by partition coefficients or surface activity.", "contents": "Correlation of physicochemical properties with absorption and metabolism of some tricyclic drugs. Octanol and dodecane partition coefficients, surface activity and adsorbability to activated charcoal were determined for six tricyclic psychotropic drugs with N-dimethylalkyl side chains. Surface activity correlated well with the partition coefficients, and all drugs obeyed the Langmuir adsorption isotherm. A correlation between the reciprocal of the death time of gold fish exposed to drugs and partition coefficients was observed. The extent to which the drugs were N-demethylated as measured by formaldehyde formed in rat liver homogenate incubations correlated with their adsorbability to activated charcoal but not with their ability to inhibit aniline-p-hydroxylase, nor was there a linear correspondence between N-DEMETHYLATION AND DRUG LIPOPHILICITY AS INDICATed by partition coefficients or surface activity."}
{"id": "PMID:26766", "title": "Investigation of possible interactions between substance P and transmitter mechanisms in the substantia nigra and corpus striatum of the rat.", "content": "The effect of substnace P (SP) on the uptake and release of radiolabelled dopamine (3H-DA), 5-hydroxytryptamine (3H-5-HT) and y-aminobutyric acid (3H-GABA) was studied in slices of rat substantia nigra and corpus triatum. SP, 10(-9) to 10(-5) m, failed to modify the uptakes of these compounds during incubations (10-90 min) with slices of either brain region. SP, 10(-6)M, had no apparent effect on the spontaneous output of any of these compounds in either substantia nigra or corpus striatum. In the corpus striatum, SP seemed to potentiate the potassium-stimulated outflow of 3H-DA and 3H-5-HT, but not 3H-GABA, while the realeases from substantia nigra were unaffected. Morphine (10(-3)M), but not met-enkephalin (5 X 10(-6)M), weakly antagonized K+- EVOKED RELEASE OF 3/-DA in the corpus striatum. These results are discussed with reference to the possible interaction of SP with transmitter mechanisms at presynaptic sites in the central nervous system.", "contents": "Investigation of possible interactions between substance P and transmitter mechanisms in the substantia nigra and corpus striatum of the rat. The effect of substnace P (SP) on the uptake and release of radiolabelled dopamine (3H-DA), 5-hydroxytryptamine (3H-5-HT) and y-aminobutyric acid (3H-GABA) was studied in slices of rat substantia nigra and corpus triatum. SP, 10(-9) to 10(-5) m, failed to modify the uptakes of these compounds during incubations (10-90 min) with slices of either brain region. SP, 10(-6)M, had no apparent effect on the spontaneous output of any of these compounds in either substantia nigra or corpus striatum. In the corpus striatum, SP seemed to potentiate the potassium-stimulated outflow of 3H-DA and 3H-5-HT, but not 3H-GABA, while the realeases from substantia nigra were unaffected. Morphine (10(-3)M), but not met-enkephalin (5 X 10(-6)M), weakly antagonized K+- EVOKED RELEASE OF 3/-DA in the corpus striatum. These results are discussed with reference to the possible interaction of SP with transmitter mechanisms at presynaptic sites in the central nervous system."}
{"id": "PMID:26767", "title": "Quisqualamine, a novel gamma-aminobutyric acid (GABA) related depressant amino acid.", "content": "A new substnace, quisqualamine, the decarboxylated analogue of quisqualic acid, predictably depressed electrical activity of neurons of the frog and rat spinal cord in vitro and of the mouse spinal cord in vivo. In the in vitro preparations, the action of quisqualamine was associated with a prolonged depolarization of primary afferent terminals which was sensitive to blockade by picrotoxin and bicuculline and which was also depressed by strychnine. This suggests an interaction of quisqualamine with presynaptic receptors for both GABA and beta-alanine. Post-synaptic actions of quisqualamine, which were less marked than those at presynaptic sites, also appeared to be predominantly GABA-mimetic in vitro, though a sensitivity to the GABA-antagonist bicuculline could not be demonstrated in vitro.", "contents": "Quisqualamine, a novel gamma-aminobutyric acid (GABA) related depressant amino acid. A new substnace, quisqualamine, the decarboxylated analogue of quisqualic acid, predictably depressed electrical activity of neurons of the frog and rat spinal cord in vitro and of the mouse spinal cord in vivo. In the in vitro preparations, the action of quisqualamine was associated with a prolonged depolarization of primary afferent terminals which was sensitive to blockade by picrotoxin and bicuculline and which was also depressed by strychnine. This suggests an interaction of quisqualamine with presynaptic receptors for both GABA and beta-alanine. Post-synaptic actions of quisqualamine, which were less marked than those at presynaptic sites, also appeared to be predominantly GABA-mimetic in vitro, though a sensitivity to the GABA-antagonist bicuculline could not be demonstrated in vitro."}
{"id": "PMID:26768", "title": "Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate.", "content": "Eight hours after intraperitoneal injections of 1.0, 2.0, and 4.0m equiv Li kg-1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2.0 m equiv kg-1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.", "contents": "Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. Eight hours after intraperitoneal injections of 1.0, 2.0, and 4.0m equiv Li kg-1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2.0 m equiv kg-1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations."}
{"id": "PMID:26769", "title": "Corticosterone concentrations in mice during ethanol drinking and withdrawal.", "content": "Consumption of an ethanol-containing diet by mice resulted in a significant increase in circulating concentrations of corticosterone which was maintained for 8 days. There were no changes in the concentrations of plasma corticosterone binding globulin. Ethanol withdrawal symptoms followed the removal of ethanol from the diet and circulating corticosterone concentrations were further increased. There was no correlation between blood ethanol and glucocorticoid concentrations during the chronic ethanol treatment. Stress related to ethanol consumption may be of greater importance than the circulating ethanol concentrations in producing the elevation in plasma glucocorticoids.", "contents": "Corticosterone concentrations in mice during ethanol drinking and withdrawal. Consumption of an ethanol-containing diet by mice resulted in a significant increase in circulating concentrations of corticosterone which was maintained for 8 days. There were no changes in the concentrations of plasma corticosterone binding globulin. Ethanol withdrawal symptoms followed the removal of ethanol from the diet and circulating corticosterone concentrations were further increased. There was no correlation between blood ethanol and glucocorticoid concentrations during the chronic ethanol treatment. Stress related to ethanol consumption may be of greater importance than the circulating ethanol concentrations in producing the elevation in plasma glucocorticoids."}
{"id": "PMID:26770", "title": "Antidotal effects of dimethyl sulphoxide against paracetamol-, bromobenzene-, and thioacetamide-induced hepatotoxicity.", "content": "In mice the hepatotoxic effects of paracetamol (0.5-1.0 g kg-1, orally) as evidenced by increased serum enzyme activities of the aminotransferases and sorbitol dehydrogenase were dose-dependently inhibited by simultaneous treatment with dimethyl sulphoxide (DMSO 0,25-1.0 g kg-1, i.p.). DMSO was also active against bromobenzene- and thioacetamide-induced hepatotoxicity, but failed to protect mice against carbon tetrachloride-induced liver damage. Hepatic glutathione depletion in mice amounting to 94% after paracetamol (0.5 g kg-1, orally) and to 60% after bromobezene (0.25 ml kg-1, orally) was dose-dependently reduced by the simultaneous administration of DMSO(0.25--1.0 G KG-1, I.P.). This indicates less conjugation of the toxic metabolites of paracetamol and bromobenzene to liver glutathione (G-SH) in the presence of DMSO.", "contents": "Antidotal effects of dimethyl sulphoxide against paracetamol-, bromobenzene-, and thioacetamide-induced hepatotoxicity. In mice the hepatotoxic effects of paracetamol (0.5-1.0 g kg-1, orally) as evidenced by increased serum enzyme activities of the aminotransferases and sorbitol dehydrogenase were dose-dependently inhibited by simultaneous treatment with dimethyl sulphoxide (DMSO 0,25-1.0 g kg-1, i.p.). DMSO was also active against bromobenzene- and thioacetamide-induced hepatotoxicity, but failed to protect mice against carbon tetrachloride-induced liver damage. Hepatic glutathione depletion in mice amounting to 94% after paracetamol (0.5 g kg-1, orally) and to 60% after bromobezene (0.25 ml kg-1, orally) was dose-dependently reduced by the simultaneous administration of DMSO(0.25--1.0 G KG-1, I.P.). This indicates less conjugation of the toxic metabolites of paracetamol and bromobenzene to liver glutathione (G-SH) in the presence of DMSO."}
{"id": "PMID:26786", "title": "Rearrangement of N-benzyl-2-cyano-2-(hydroxyimino)acetamide.", "content": "The reduction of N-benzyl-2-cyano-2-(hydroxyimino)acetamide resulted in the formation of N-benzyl-1,2-ethanediamine and N-benzyl-N'-methyl-1,2-ethanediamine in approximately an equimolar ratio. The formation of the two unexpected products is explained by the migration of a cyano group in a Beckmann-type rearrangement.", "contents": "Rearrangement of N-benzyl-2-cyano-2-(hydroxyimino)acetamide. The reduction of N-benzyl-2-cyano-2-(hydroxyimino)acetamide resulted in the formation of N-benzyl-1,2-ethanediamine and N-benzyl-N'-methyl-1,2-ethanediamine in approximately an equimolar ratio. The formation of the two unexpected products is explained by the migration of a cyano group in a Beckmann-type rearrangement."}
{"id": "PMID:26787", "title": "Interaction of tricyclic antipsychotic and antidepressant drugs with 1-anilino-8-naphthalenesulfonic acid.", "content": "The binding of 1-anilino-8-naphthalenesulfonic acid to selected tricyclic antipsychotic and antidepressant drugs was studied by fluorescence spectroscopy. The acid exhibited an increase in fluorescence intensity accompanied by a hypsochromic shift of the emission lambdamax in the presence of these drugs. These fluorescence characteristics, in addition to those of acid-drug complexes after addition of potassium chloride or urea, suggested that binding was hydrophobic. The spectra also provided evidence regarding the importance of certain structural features of drugs in determining the nature of binding.", "contents": "Interaction of tricyclic antipsychotic and antidepressant drugs with 1-anilino-8-naphthalenesulfonic acid. The binding of 1-anilino-8-naphthalenesulfonic acid to selected tricyclic antipsychotic and antidepressant drugs was studied by fluorescence spectroscopy. The acid exhibited an increase in fluorescence intensity accompanied by a hypsochromic shift of the emission lambdamax in the presence of these drugs. These fluorescence characteristics, in addition to those of acid-drug complexes after addition of potassium chloride or urea, suggested that binding was hydrophobic. The spectra also provided evidence regarding the importance of certain structural features of drugs in determining the nature of binding."}
{"id": "PMID:26788", "title": "Solubility studies of silver sulfonamides.", "content": "The solubilities of silver sulfapyridine, silver sulfamethazine, and silver sulfamethizole as a function of pH were determined in nitric acid-potassium nitrate, acetate, and sulfonic acid buffers. All silver sulfonamides showed an increase in solubility with increasing hydrogen-ion concentration, a behavior which closely paralleled the protonation of the p-amino function of the sulfonamide. A silver-ion selective electrode was used to measure silver-ion concentration in solution and the methods of known subtraction and known addition were used to measure total silver. Both silver sulfamethizole and silver sulfamethazine were ionized completely in solution. Silver sulfapyridine was ionized completely only in the more acidic pH 2-3 range. A comparison of the physical properties of the silver salts for which mortality studies were available revealed a unique set of properties for silver sulfadiazine.", "contents": "Solubility studies of silver sulfonamides. The solubilities of silver sulfapyridine, silver sulfamethazine, and silver sulfamethizole as a function of pH were determined in nitric acid-potassium nitrate, acetate, and sulfonic acid buffers. All silver sulfonamides showed an increase in solubility with increasing hydrogen-ion concentration, a behavior which closely paralleled the protonation of the p-amino function of the sulfonamide. A silver-ion selective electrode was used to measure silver-ion concentration in solution and the methods of known subtraction and known addition were used to measure total silver. Both silver sulfamethizole and silver sulfamethazine were ionized completely in solution. Silver sulfapyridine was ionized completely only in the more acidic pH 2-3 range. A comparison of the physical properties of the silver salts for which mortality studies were available revealed a unique set of properties for silver sulfadiazine."}
{"id": "PMID:26789", "title": "Ketonic oxidation products of cyclobarbital.", "content": "Chemical or biochemical oxidation of cyclobarbital yielded 5-(3-oxo-1-cyclohexen-1-yl)-5-ethyl -2,4,6,- (1H,3H,5H)-pyrimidinetrione, and photochemical oxidation gave 5-(6-oxo-1-cyclohexen-1-yl)-5-ethyl-2,4,6-(1H,3H,3H)-pyrimidinetrione. These compounds were isolated and purified by TLC, and their structures were determined by UV, IR, NMR, and mass spectral data; the crystalline structure was determined by X-ray diffraction.", "contents": "Ketonic oxidation products of cyclobarbital. Chemical or biochemical oxidation of cyclobarbital yielded 5-(3-oxo-1-cyclohexen-1-yl)-5-ethyl -2,4,6,- (1H,3H,5H)-pyrimidinetrione, and photochemical oxidation gave 5-(6-oxo-1-cyclohexen-1-yl)-5-ethyl-2,4,6-(1H,3H,3H)-pyrimidinetrione. These compounds were isolated and purified by TLC, and their structures were determined by UV, IR, NMR, and mass spectral data; the crystalline structure was determined by X-ray diffraction."}
{"id": "PMID:26790", "title": "Colorimetric determination of nadolol in tablets.", "content": "Nadolol was extracted from tablet excipients with an acidic potassium chloride solution. The drug was oxidized with periodic acid, and the resulting aldehyde was reacted with 2,4-dinitrophenylhydrazine to form the corresponding hydrazone. Excess reagent was removed with a cupric chloride solution. The hydrazone was extracted into chloroform, and its absorbance was measured at the 352-nm maximum.", "contents": "Colorimetric determination of nadolol in tablets. Nadolol was extracted from tablet excipients with an acidic potassium chloride solution. The drug was oxidized with periodic acid, and the resulting aldehyde was reacted with 2,4-dinitrophenylhydrazine to form the corresponding hydrazone. Excess reagent was removed with a cupric chloride solution. The hydrazone was extracted into chloroform, and its absorbance was measured at the 352-nm maximum."}
{"id": "PMID:26791", "title": "Possible ion-pair-mediated absorption of mixidine I: partitioning and lethality studies.", "content": "Mixidine, a very soluble base which is completely ionized in all physiological fluids, was found to form ion-pairs as demonstrated by its ability to partition into 1-butanol from acidic solutions. A similar relationship was observed for the effect of acids on the absorption of intraduodenally and orally administered solutions of mixidine in rats (as determined by lethality). Studies also demonstrated that the pH-lethality effects were not specific for a particular counterion. Mixidine was more lethal when administered intraduodenally than when administered orally, and the counterions per se were not lethal in the doses used.", "contents": "Possible ion-pair-mediated absorption of mixidine I: partitioning and lethality studies. Mixidine, a very soluble base which is completely ionized in all physiological fluids, was found to form ion-pairs as demonstrated by its ability to partition into 1-butanol from acidic solutions. A similar relationship was observed for the effect of acids on the absorption of intraduodenally and orally administered solutions of mixidine in rats (as determined by lethality). Studies also demonstrated that the pH-lethality effects were not specific for a particular counterion. Mixidine was more lethal when administered intraduodenally than when administered orally, and the counterions per se were not lethal in the doses used."}
{"id": "PMID:26792", "title": "Possible ion-pair-mediated absorption of mixidine II: plasma levels and histology.", "content": "Plasma intact 14C-mixidine levels in rats increased when the drug was administered intraduodenally with 1:3 and 1:5 molar ratios of 2-naphthalenesulfonic acid. Upon histological examination of the duodenums, similar doses of mixidine combined with 2-naphthalenesulfonic acid produced no dose-related lesions. These and previous observations demonstrate that mixidine absorption may be enhanced by ion-pair formation.", "contents": "Possible ion-pair-mediated absorption of mixidine II: plasma levels and histology. Plasma intact 14C-mixidine levels in rats increased when the drug was administered intraduodenally with 1:3 and 1:5 molar ratios of 2-naphthalenesulfonic acid. Upon histological examination of the duodenums, similar doses of mixidine combined with 2-naphthalenesulfonic acid produced no dose-related lesions. These and previous observations demonstrate that mixidine absorption may be enhanced by ion-pair formation."}
{"id": "PMID:26793", "title": "Simple GLC analysis of anticonvulsant drugs in commercial dosage forms.", "content": "A simple, specific GLC procedure is described for the analysis of one sedative and six anticonvulsant drugs in pharmaceutical dosage forms. Sample aliquots of ethotoin, glutethimide, mephenytoin, methsuximide, and phensuximide were shaken with or extracted into ethyl acetate, diluted with the internal standard (diphenyl phthalate) solution, injected into a gas chromatograph, and eluted from a methylsilicon column. Primidone and phenytoin samples (extracted as the free acid) required derivatization with N,O-bis(trimethylsilyl)acetamide prior to chromatography. The same temperature programming conditions and flow rate settings were used for all seven drugs. The GLC results agreed well with those obtained using the pharmacopeial methods.", "contents": "Simple GLC analysis of anticonvulsant drugs in commercial dosage forms. A simple, specific GLC procedure is described for the analysis of one sedative and six anticonvulsant drugs in pharmaceutical dosage forms. Sample aliquots of ethotoin, glutethimide, mephenytoin, methsuximide, and phensuximide were shaken with or extracted into ethyl acetate, diluted with the internal standard (diphenyl phthalate) solution, injected into a gas chromatograph, and eluted from a methylsilicon column. Primidone and phenytoin samples (extracted as the free acid) required derivatization with N,O-bis(trimethylsilyl)acetamide prior to chromatography. The same temperature programming conditions and flow rate settings were used for all seven drugs. The GLC results agreed well with those obtained using the pharmacopeial methods."}
{"id": "PMID:26794", "title": "Effects of patulin on the kinetics of substrate and cationic ligand activation of adenosine triphosphatase in mouse brain.", "content": "Patulin (4-hydroxy-4H-furo[3,2-c]pyran-2(6H)-one), a carcinogenic lactone produced as a major metabolite by several fungi, inhibited the Mg++-dependent Na+-K+ activated adenosine triphosphatase (ATPase) activity of mouse brain microsomal fractions with an estimated IC50 of 3.0 X 10(-4) M. Inhibition was concentration dependent. Hydrolysis of ATP was linear with both time and enzyme concentration either with or without patulin in reaction mixtures. Altered pH and activity curves for Na+-K+ ATPase demonstrated comparable inhibition by patulin in buffered acidic ranges through an optimum of 7.5, followed by a reduction of toxicity to this system at higher alkaline pH. Kinetic studies of cationic-substrate activation of Na+-K+ ATPase indicated noncompetitive inhibition with respect to ATP (at low affinity nucleotide-directed sites) and Na+ (in the presence of low, noninterfering concentrations of K+). Competitive inhibition with respect to activation of the Na+-k+-stimulated activity and K+-stimulated p-nitrophenyl phosphatase activity of the enzyme system was indicated by altered binding site parameters without change in apparent Vmax in the presence of patulin. Activity was partially restored by washing. Preincubation of patulin with dithiothreitol or glutathione protected the enzyme from inhibition. Results suggest that patulin exerted its effect on Na+-K+ ATPase either directly by interfering with K+ binding or indirectly by inducing a conformational change in the enzyme.", "contents": "Effects of patulin on the kinetics of substrate and cationic ligand activation of adenosine triphosphatase in mouse brain. Patulin (4-hydroxy-4H-furo[3,2-c]pyran-2(6H)-one), a carcinogenic lactone produced as a major metabolite by several fungi, inhibited the Mg++-dependent Na+-K+ activated adenosine triphosphatase (ATPase) activity of mouse brain microsomal fractions with an estimated IC50 of 3.0 X 10(-4) M. Inhibition was concentration dependent. Hydrolysis of ATP was linear with both time and enzyme concentration either with or without patulin in reaction mixtures. Altered pH and activity curves for Na+-K+ ATPase demonstrated comparable inhibition by patulin in buffered acidic ranges through an optimum of 7.5, followed by a reduction of toxicity to this system at higher alkaline pH. Kinetic studies of cationic-substrate activation of Na+-K+ ATPase indicated noncompetitive inhibition with respect to ATP (at low affinity nucleotide-directed sites) and Na+ (in the presence of low, noninterfering concentrations of K+). Competitive inhibition with respect to activation of the Na+-k+-stimulated activity and K+-stimulated p-nitrophenyl phosphatase activity of the enzyme system was indicated by altered binding site parameters without change in apparent Vmax in the presence of patulin. Activity was partially restored by washing. Preincubation of patulin with dithiothreitol or glutathione protected the enzyme from inhibition. Results suggest that patulin exerted its effect on Na+-K+ ATPase either directly by interfering with K+ binding or indirectly by inducing a conformational change in the enzyme."}
{"id": "PMID:26795", "title": "Beta adrenergic blockade, regional left ventricular blood flow and ST-segment elevation in canine experimental myocardial ischemia.", "content": "The effects of dl-propranolol, d-propranolol, dl-pindolol and dl-practolol on regional myocardial blood flow (assessed by means of tracer microspheres) and on ST-segment elevation in ischemic and nonischemic areas of the canine left ventricle have been investigated. dl-Propranolol and dl-pindolol, but not dl-practolol and d-propranolol, induced blood flow redistribution from the epicardium to the endocardium both in ischemic and nonischemic areas. dl-Propranolol-induced redistribution was abolished by atrial pacing at the control heart rate value. These results indicate that the redistribution phenomenon only occurs if both a bradycardia-inducing beta1 adrenoreceptor blockade and a coronary vessels beta2 adrenoceptor blockade are simultaneously achieved. All four drugs significantly decreased ST-segment elevation in ischemic areas. Under atrial pacing, this effect was abolished with dl-practolol but only reduced with dl- and d-propranol, suggesting that, besides bradycardia, membrane stabilization might be involved in protection against ST-segment elevation in ischemic areas.", "contents": "Beta adrenergic blockade, regional left ventricular blood flow and ST-segment elevation in canine experimental myocardial ischemia. The effects of dl-propranolol, d-propranolol, dl-pindolol and dl-practolol on regional myocardial blood flow (assessed by means of tracer microspheres) and on ST-segment elevation in ischemic and nonischemic areas of the canine left ventricle have been investigated. dl-Propranolol and dl-pindolol, but not dl-practolol and d-propranolol, induced blood flow redistribution from the epicardium to the endocardium both in ischemic and nonischemic areas. dl-Propranolol-induced redistribution was abolished by atrial pacing at the control heart rate value. These results indicate that the redistribution phenomenon only occurs if both a bradycardia-inducing beta1 adrenoreceptor blockade and a coronary vessels beta2 adrenoceptor blockade are simultaneously achieved. All four drugs significantly decreased ST-segment elevation in ischemic areas. Under atrial pacing, this effect was abolished with dl-practolol but only reduced with dl- and d-propranol, suggesting that, besides bradycardia, membrane stabilization might be involved in protection against ST-segment elevation in ischemic areas."}
{"id": "PMID:26797", "title": "Liberation of cyanide from alpha-aminonitriles relative to amygdalin.", "content": "A series of aminoitriles have been synthesized and studied whose nonenzymatic dissociation with release of cyanide may be varied by modest alteration of their molecular structure from that obtained with nonenzymatic dissociation of amygdalin to that obtained from enzymatic dissociation of amygdalin by substantial quantities of beta-glucosidase. The relationship between such alterations in molecular structure and nonenzymatic dissociation is discussed. A combination of the results of these studies and studies relating molecular structure to physical localization propensity in tumors has potential in the design of chemotherapeutic agents.", "contents": "Liberation of cyanide from alpha-aminonitriles relative to amygdalin. A series of aminoitriles have been synthesized and studied whose nonenzymatic dissociation with release of cyanide may be varied by modest alteration of their molecular structure from that obtained with nonenzymatic dissociation of amygdalin to that obtained from enzymatic dissociation of amygdalin by substantial quantities of beta-glucosidase. The relationship between such alterations in molecular structure and nonenzymatic dissociation is discussed. A combination of the results of these studies and studies relating molecular structure to physical localization propensity in tumors has potential in the design of chemotherapeutic agents."}
{"id": "PMID:26798", "title": "Inhibition of sympathetic nervous system by histamine:studies with H1- and H2-receptor antagonists.", "content": "A study was designed to investigate the effect of histamine on sympathetic transmission to the myocardium in pentobarbital-anesthetized dogs. Intravenous infusion of histamine (1.0 and 2.0 microgram/kg/min) produced dose-related decreases in blood pressure and caused significant impairment of cardioacceleration observed during stimulation of the right postganglionic cardiac sympathetic nerve fibers. Positive chronotropic effects of intravenously administered norepinephrine as well as tyramine were not altered during histamine infusion. Blockade of neuronal reuptake with desipramine did not modify the inhibitory action of histamine on sympathetic nerve function. Prior administration of mepyramine (pyrilamine), a histamine type H1-receptor antagonist caused partial attenuation of the depressor action of histamine, but did not prevent histamine-induced inhibition of neurogenic function. Further treatment with metiamide, a histamine type H2-receptor antagonist caused nearly complete attenuation of the depressor response to histamine and also significantly antagonized the inhibitory action of histamine on sympathetic transmission to the myocardium. It is concluded that while the depressor action of histamine is due to the activation of both H1- as well as H2-receptors, histamine causes impairment of sympathetic nerve function to the myocardium by acting on H2-receptors which may be located on sympathetic nerve terminals.", "contents": "Inhibition of sympathetic nervous system by histamine:studies with H1- and H2-receptor antagonists. A study was designed to investigate the effect of histamine on sympathetic transmission to the myocardium in pentobarbital-anesthetized dogs. Intravenous infusion of histamine (1.0 and 2.0 microgram/kg/min) produced dose-related decreases in blood pressure and caused significant impairment of cardioacceleration observed during stimulation of the right postganglionic cardiac sympathetic nerve fibers. Positive chronotropic effects of intravenously administered norepinephrine as well as tyramine were not altered during histamine infusion. Blockade of neuronal reuptake with desipramine did not modify the inhibitory action of histamine on sympathetic nerve function. Prior administration of mepyramine (pyrilamine), a histamine type H1-receptor antagonist caused partial attenuation of the depressor action of histamine, but did not prevent histamine-induced inhibition of neurogenic function. Further treatment with metiamide, a histamine type H2-receptor antagonist caused nearly complete attenuation of the depressor response to histamine and also significantly antagonized the inhibitory action of histamine on sympathetic transmission to the myocardium. It is concluded that while the depressor action of histamine is due to the activation of both H1- as well as H2-receptors, histamine causes impairment of sympathetic nerve function to the myocardium by acting on H2-receptors which may be located on sympathetic nerve terminals."}
{"id": "PMID:26800", "title": "The role of peripheral catecholamines in oxotremorine tremor in the rat and its antagonism by beta adrenoceptor blocking agents.", "content": "Oxotremorine, 0.25 mg/kg, produces marked tremor in the rat, which is abolished by scopolamine, 0.5 mg/kg, and is substantially reduced in intensity and duration both by adrenalmedullectomy and by chemical sympathectomy with 6-hydroxydopamine. Oxotremorine increases plasma norepinephrine from 0.62 +/- 0.07 to 3.01 +/- 0.47 ng/ml and plasma epinephrine, from 0.82 +/- 0.14 to 3.42 +/- 0.48 ng/ml, in conscious unrestrained rats. l-Propranolol (0.5-2.5 mg/kg) reduces tremor, and at 2.5 mg/kg is more effective than either chemical sympathectomy or adrenal demedullation. d-Propranolol and sotalol are also active at 4 and 10 times the dose of l-propranolol, respectively. l-Propranolol does not prevent the rise in catecholamines induced by oxotremorine. It is suggested that stimulation of central muscarinic receptors causes tremor by a combination of two effects. There is an increase in cholinergic influence to motor efferents accompanied by an activation of the sympathoadrenal system to release catecholamines which augment tremor by stimulation of beta2 adrenoceptors.", "contents": "The role of peripheral catecholamines in oxotremorine tremor in the rat and its antagonism by beta adrenoceptor blocking agents. Oxotremorine, 0.25 mg/kg, produces marked tremor in the rat, which is abolished by scopolamine, 0.5 mg/kg, and is substantially reduced in intensity and duration both by adrenalmedullectomy and by chemical sympathectomy with 6-hydroxydopamine. Oxotremorine increases plasma norepinephrine from 0.62 +/- 0.07 to 3.01 +/- 0.47 ng/ml and plasma epinephrine, from 0.82 +/- 0.14 to 3.42 +/- 0.48 ng/ml, in conscious unrestrained rats. l-Propranolol (0.5-2.5 mg/kg) reduces tremor, and at 2.5 mg/kg is more effective than either chemical sympathectomy or adrenal demedullation. d-Propranolol and sotalol are also active at 4 and 10 times the dose of l-propranolol, respectively. l-Propranolol does not prevent the rise in catecholamines induced by oxotremorine. It is suggested that stimulation of central muscarinic receptors causes tremor by a combination of two effects. There is an increase in cholinergic influence to motor efferents accompanied by an activation of the sympathoadrenal system to release catecholamines which augment tremor by stimulation of beta2 adrenoceptors."}
{"id": "PMID:26804", "title": "Synthesis and pharmacological activity and some derivatives of 1-phenyl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one.", "content": "4-N-Alkylamino derivatives and corresponding ammonium quaternary salts of tetrahydro-1,4-benzodiazepin-5-one were synthesized and evaluated for psychotropic activity in mice by ip via. This study was also extended to some nitro and amino derivatives of tetrahydro-1,4-benzodiazepin-5-one. Compounds were devoid of tranquilizing activity and in comparison with two classical benzodiazepines, chlordiazepoxide and diazepam, they showed high toxicity and little or no effect on motor coordination, motor activity, and maximal electroshock. On some \"in vitro\" tests the compounds exhibited pharmacological properties when they were used at high concentrations.", "contents": "Synthesis and pharmacological activity and some derivatives of 1-phenyl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one. 4-N-Alkylamino derivatives and corresponding ammonium quaternary salts of tetrahydro-1,4-benzodiazepin-5-one were synthesized and evaluated for psychotropic activity in mice by ip via. This study was also extended to some nitro and amino derivatives of tetrahydro-1,4-benzodiazepin-5-one. Compounds were devoid of tranquilizing activity and in comparison with two classical benzodiazepines, chlordiazepoxide and diazepam, they showed high toxicity and little or no effect on motor coordination, motor activity, and maximal electroshock. On some \"in vitro\" tests the compounds exhibited pharmacological properties when they were used at high concentrations."}
{"id": "PMID:26805", "title": "A method for the isolation of Bacteroides melaninogenicus from the human mouth.", "content": "Isolation procedures involving the direct plating of specimens and the use of selective, non-selective, transport and enrichment media were compared in respect of their value for the recovery of Bacteroides melaninogenicus from the gingival sulcus. A selective medium containing kanamycin and vancomycin enhanced the recovery rate of B. melaninogenicus. VMGII transport medium was convenient to use and gave as good a recovery rate as that obtained with plates directly inoculated in the clinic.", "contents": "A method for the isolation of Bacteroides melaninogenicus from the human mouth. Isolation procedures involving the direct plating of specimens and the use of selective, non-selective, transport and enrichment media were compared in respect of their value for the recovery of Bacteroides melaninogenicus from the gingival sulcus. A selective medium containing kanamycin and vancomycin enhanced the recovery rate of B. melaninogenicus. VMGII transport medium was convenient to use and gave as good a recovery rate as that obtained with plates directly inoculated in the clinic."}
{"id": "PMID:26807", "title": "Amino acid activation with adenosine 5'-phosphorimidazolide.", "content": "Amino acids are activated by reaction with adenosine 5'-phosphorimidazolide in aqueous imidazole buffers. If adenosine 5'-(O-methylphosphate), an analogue of the 3'-terminus of t-RNA is present, 2'(3')-O-aminoacyladenosine 5'-(O-methylphosphate) is formed. Fifteen percent of this compound accumulated at pH 5.8, but less was formed at higher pHs. The highest efficiency of utilization if ImpA attained in our experiments was about 24%. Analogous reactions occured with several other amino acids, including a number that have functional side-chains.", "contents": "Amino acid activation with adenosine 5'-phosphorimidazolide. Amino acids are activated by reaction with adenosine 5'-phosphorimidazolide in aqueous imidazole buffers. If adenosine 5'-(O-methylphosphate), an analogue of the 3'-terminus of t-RNA is present, 2'(3')-O-aminoacyladenosine 5'-(O-methylphosphate) is formed. Fifteen percent of this compound accumulated at pH 5.8, but less was formed at higher pHs. The highest efficiency of utilization if ImpA attained in our experiments was about 24%. Analogous reactions occured with several other amino acids, including a number that have functional side-chains."}
{"id": "PMID:26808", "title": "Intracellular electrolytes in erythrocytes during and after shock: relation to impaired consciousness.", "content": "Of 32 patients in shock and catabolic state following shock with impaired consciousness 31 exhibited raised sodium content in their erythrocytes. On the assumption that the erythrocyte membrane acts the same as nerve cell membrane, the hypofunction of erythrocyte membrane may result in impaired consciousness. The hypofunction of erythrocyte membrane is assumed by its increased permeability in shock. A positive osmotic discrepancy between measured and calculated levels denotes altered membranous permeability. Subjectively, impaired consciousness was evaluated by clinical grading. Meanwhile, as a trial of quantification of conscious levels, we applied a new technique of analysis of power spectrum obtained by computer on the autocorrelogram of the EEG during intermittent photic stimulation. This new analytic method was useful in evaluating objective changes of cerebral function. There was a good correlation between raised sodium content in erythrocytes and depressed power spectrum. The degree of increased sodium in erythrocytes seems to correlate with patients' clinical prognosis.", "contents": "Intracellular electrolytes in erythrocytes during and after shock: relation to impaired consciousness. Of 32 patients in shock and catabolic state following shock with impaired consciousness 31 exhibited raised sodium content in their erythrocytes. On the assumption that the erythrocyte membrane acts the same as nerve cell membrane, the hypofunction of erythrocyte membrane may result in impaired consciousness. The hypofunction of erythrocyte membrane is assumed by its increased permeability in shock. A positive osmotic discrepancy between measured and calculated levels denotes altered membranous permeability. Subjectively, impaired consciousness was evaluated by clinical grading. Meanwhile, as a trial of quantification of conscious levels, we applied a new technique of analysis of power spectrum obtained by computer on the autocorrelogram of the EEG during intermittent photic stimulation. This new analytic method was useful in evaluating objective changes of cerebral function. There was a good correlation between raised sodium content in erythrocytes and depressed power spectrum. The degree of increased sodium in erythrocytes seems to correlate with patients' clinical prognosis."}
{"id": "PMID:26809", "title": "Transfection of Streptococcus pneumoniae with bacteriophage DNA.", "content": "It was possible to transfect Streptococcus pneumoniae with DNA obtained from a newly isolated bacteriophage, diplophage-4 (Dp-4). Optimal frequency of transfection (0.9%) required the use of a nuclease-defective mutant; with wild-type bacteria, the transfection frequency was about 100-fold lower. Transfection requires physiological conditions that appear to be similar to the competent state needed for genetic transformation (A. Tomasz, J. Bacteriol. 91:1050--1061, 1966).", "contents": "Transfection of Streptococcus pneumoniae with bacteriophage DNA. It was possible to transfect Streptococcus pneumoniae with DNA obtained from a newly isolated bacteriophage, diplophage-4 (Dp-4). Optimal frequency of transfection (0.9%) required the use of a nuclease-defective mutant; with wild-type bacteria, the transfection frequency was about 100-fold lower. Transfection requires physiological conditions that appear to be similar to the competent state needed for genetic transformation (A. Tomasz, J. Bacteriol. 91:1050--1061, 1966)."}
{"id": "PMID:26810", "title": "Helper-independent transformation by unintegrated Harvey sarcoma virus DNA.", "content": "We have studied the unintegrated infectious DNA of Harvey sarcoma virus (Ha-SV) and Moloney leukemia virus (Mo-MuLV). The source of infectious viral DNA was the Hirt supernatant fraction from cells acutely infected with Ha-SV and Mo-MuLV. To obtain a direct quantitative assay for infectious viral DNA, recipient mouse cells were first exposed to calcium phosphate-precipitated viral DNA and then treated with dimethyl sulfoxide. Infectivity was monitored by focus formation for Ha-SV and XC plaque formation for Mo-MuLV. The viral DNA titration pattern followed single-hit kinetics for both foci and plaques, indicating that a single molecule carried information for each function. Focus-forming and plaque-forming activity were present in different molecules, since these two biological activities could be separated from each other by agarose gel electrophoresis. The focus-forming molecule was linear DNA with a molecular weight of about 4 x 10(6) daltons. The focus-forming activity of the viral DNA was sensitive to EcoRI and resistant to XhoI restriction endonucleases, whereas the plaque-forming activity was resistant to EcoRI and sensitive to XhoI. The generation of helper-independent foci indicates that Ha-SV DNA can transform mouse cells in the absence of helper virus or its proteins.", "contents": "Helper-independent transformation by unintegrated Harvey sarcoma virus DNA. We have studied the unintegrated infectious DNA of Harvey sarcoma virus (Ha-SV) and Moloney leukemia virus (Mo-MuLV). The source of infectious viral DNA was the Hirt supernatant fraction from cells acutely infected with Ha-SV and Mo-MuLV. To obtain a direct quantitative assay for infectious viral DNA, recipient mouse cells were first exposed to calcium phosphate-precipitated viral DNA and then treated with dimethyl sulfoxide. Infectivity was monitored by focus formation for Ha-SV and XC plaque formation for Mo-MuLV. The viral DNA titration pattern followed single-hit kinetics for both foci and plaques, indicating that a single molecule carried information for each function. Focus-forming and plaque-forming activity were present in different molecules, since these two biological activities could be separated from each other by agarose gel electrophoresis. The focus-forming molecule was linear DNA with a molecular weight of about 4 x 10(6) daltons. The focus-forming activity of the viral DNA was sensitive to EcoRI and resistant to XhoI restriction endonucleases, whereas the plaque-forming activity was resistant to EcoRI and sensitive to XhoI. The generation of helper-independent foci indicates that Ha-SV DNA can transform mouse cells in the absence of helper virus or its proteins."}
{"id": "PMID:26811", "title": "Lymphangiography in patients with malignancy in a non-descended testicle.", "content": "Lymphangiography was performed on 23 patients with malignancy in non-descended testicles, 14 of whom had seminomatous and 9 non-seminomatous tumors. Lymph node metastases were shown by lymphangiography in 8 patients: 3 in lumbar nodes, 1 in iliac nodes alone and 4 in lumbar and iliac lymph nodes. Microscopic metastases were shown in lumbar nodes at retroperitoneal lymph node dissection in 2 patients when the lymphangiograms were negative. Iliac lymph node metastases are rare in testicular tumors but may be seen in tumors of non-descended testicles, alone or in combination with lumbar metastatic disease. This information is extremely important for the radiologist as well as the clinician in the management of patients.", "contents": "Lymphangiography in patients with malignancy in a non-descended testicle. Lymphangiography was performed on 23 patients with malignancy in non-descended testicles, 14 of whom had seminomatous and 9 non-seminomatous tumors. Lymph node metastases were shown by lymphangiography in 8 patients: 3 in lumbar nodes, 1 in iliac nodes alone and 4 in lumbar and iliac lymph nodes. Microscopic metastases were shown in lumbar nodes at retroperitoneal lymph node dissection in 2 patients when the lymphangiograms were negative. Iliac lymph node metastases are rare in testicular tumors but may be seen in tumors of non-descended testicles, alone or in combination with lumbar metastatic disease. This information is extremely important for the radiologist as well as the clinician in the management of patients."}
{"id": "PMID:26812", "title": "Screening urography in asymptomatic cryptorchid patients.", "content": "Excretory urograms in 140 cryptorchid patients free of associated urologic symptoms are reviewed. Our findings are presented and compared to those of previously reported series. Our results do not indicate a specific indication for the routine use of excretory urography in asymptomatic male subjects with cryptorchidism.", "contents": "Screening urography in asymptomatic cryptorchid patients. Excretory urograms in 140 cryptorchid patients free of associated urologic symptoms are reviewed. Our findings are presented and compared to those of previously reported series. Our results do not indicate a specific indication for the routine use of excretory urography in asymptomatic male subjects with cryptorchidism."}
{"id": "PMID:26813", "title": "Anorchism versus cryptorchidism: the importance of a diligent search for intra-abdominal testes.", "content": "We reviewed 13 cases of testicular tumors arising in cryptorchid, intra-abdominal testes. All types of germinal neoplasms were found, seminoma being the most common. Of the 13 patients 5 had undergone limited exploration previously, with no testis being identified and, thus, were thought to have had unilateral anorchism. The importance of a thorough exploration of the peritoneal cavity is emphasized.", "contents": "Anorchism versus cryptorchidism: the importance of a diligent search for intra-abdominal testes. We reviewed 13 cases of testicular tumors arising in cryptorchid, intra-abdominal testes. All types of germinal neoplasms were found, seminoma being the most common. Of the 13 patients 5 had undergone limited exploration previously, with no testis being identified and, thus, were thought to have had unilateral anorchism. The importance of a thorough exploration of the peritoneal cavity is emphasized."}
{"id": "PMID:26814", "title": "Prostatic utricle cysts (m\u00fcllerian duct cysts).", "content": "A series of 88 male patients with prostatic utricle cysts (m\u00fcllerian duct) has been compiled by adding our 3 patients to 85 cases reported. Irritative lower urinary tract symptoms were the most common presenting complaint (42 per cent), while lower obstructive symptoms were noted in 29 per cent. Of the 20 clinical case reports in boys 25 per cent presented with epididymitis often in an undescended gonad. A cystic rectal mass found in half of the patients represents the most common presenting sign, while hypospadias occurred in a fourth. Unilateral renal dysgenesis or agenesis was associated in 10 per cent of the reports. While the suprapubic surgical approach to excision has been used most commonly it has proved unsatisfactory in two-thirds of the cases. The posterior approach was used successfully in 2 boys with preservation of erectile potency in both. The wide spectrum of histopathology of these cysts prevents clear characterization. A 3% incidence of malignancy in prostatic utricle cysts is noted.", "contents": "Prostatic utricle cysts (m\u00fcllerian duct cysts). A series of 88 male patients with prostatic utricle cysts (m\u00fcllerian duct) has been compiled by adding our 3 patients to 85 cases reported. Irritative lower urinary tract symptoms were the most common presenting complaint (42 per cent), while lower obstructive symptoms were noted in 29 per cent. Of the 20 clinical case reports in boys 25 per cent presented with epididymitis often in an undescended gonad. A cystic rectal mass found in half of the patients represents the most common presenting sign, while hypospadias occurred in a fourth. Unilateral renal dysgenesis or agenesis was associated in 10 per cent of the reports. While the suprapubic surgical approach to excision has been used most commonly it has proved unsatisfactory in two-thirds of the cases. The posterior approach was used successfully in 2 boys with preservation of erectile potency in both. The wide spectrum of histopathology of these cysts prevents clear characterization. A 3% incidence of malignancy in prostatic utricle cysts is noted."}
{"id": "PMID:26815", "title": "Reconstruction of the urinary tract in prune belly uropathy.", "content": "Ten patients with prune bell uropathy, including 7 neonates, were treated with extensive surgical tailoring of the upper urinary tracts using primarily the upper ureteral segment. Simultaneous transabdominal orchiopexy, particularly in the neonate, is described as a useful adjunct. Our early results in these patients justify this aggressive approach.", "contents": "Reconstruction of the urinary tract in prune belly uropathy. Ten patients with prune bell uropathy, including 7 neonates, were treated with extensive surgical tailoring of the upper urinary tracts using primarily the upper ureteral segment. Simultaneous transabdominal orchiopexy, particularly in the neonate, is described as a useful adjunct. Our early results in these patients justify this aggressive approach."}
{"id": "PMID:26818", "title": "Treatment of the agitated patient with an organic brain disorder.", "content": "Agitated patients with organic brain disorders represent relatively common diagnostic and management problems. Therapeutic failures usually result from a failure to understand the patient's disturbed behavior, the staff's emotional response to the patient's behavior, or neglect of the biological cause and ineffective use of medication. Effective management depends on continued monitoring of the patient's mental status and physical condition.", "contents": "Treatment of the agitated patient with an organic brain disorder. Agitated patients with organic brain disorders represent relatively common diagnostic and management problems. Therapeutic failures usually result from a failure to understand the patient's disturbed behavior, the staff's emotional response to the patient's behavior, or neglect of the biological cause and ineffective use of medication. Effective management depends on continued monitoring of the patient's mental status and physical condition."}
{"id": "PMID:26821", "title": "[Comparative examinations of gastric juice in healthy infants and in infants suffering from enteritis (author's transl)].", "content": "There are significant differences between the shapes of curves of gastric juice volume, acid quantity, pH levels, and peptic activity, in the three age groups of healthy infants under examination. Significant differences are also seen in all three age groups with regard to the quantity of acid calculated in relation to 1 ml gastric juice, as well as the relative peptic activity (volume activity). The amount of gastric juice is proportional to the bodyweight and body surface of the infants, whereas acid concentration and peptic volume activity show a relatively steeper increase.", "contents": "[Comparative examinations of gastric juice in healthy infants and in infants suffering from enteritis (author's transl)]. There are significant differences between the shapes of curves of gastric juice volume, acid quantity, pH levels, and peptic activity, in the three age groups of healthy infants under examination. Significant differences are also seen in all three age groups with regard to the quantity of acid calculated in relation to 1 ml gastric juice, as well as the relative peptic activity (volume activity). The amount of gastric juice is proportional to the bodyweight and body surface of the infants, whereas acid concentration and peptic volume activity show a relatively steeper increase."}
{"id": "PMID:26823", "title": "[Possibility of using higher plants in a life-support system on the moon].", "content": "The paper discusses the possibility of repeated termination of plant vegetation by prolonged darkness approximating the lunar night. This may be helpful for the incorporation of higher plants into the life support system of lunar bases, the solar light being used for illumination. In this connection vegetables (beet Bordeaux, turnip Petrovskaya, carrot Chantanet, dill, radish Virovsky white) and wheat (variety Sonora) were cultivated during the lunar light-dark cycle (i. e. 15 day light: 15 day dark). The experiments demonstrated that traditional plant products can be obtained under the conditions of lunar photoperiod. Grain of wheat grown during the lunar photoperiod were tested as seed material for further cultivation under similar conditions.", "contents": "[Possibility of using higher plants in a life-support system on the moon]. The paper discusses the possibility of repeated termination of plant vegetation by prolonged darkness approximating the lunar night. This may be helpful for the incorporation of higher plants into the life support system of lunar bases, the solar light being used for illumination. In this connection vegetables (beet Bordeaux, turnip Petrovskaya, carrot Chantanet, dill, radish Virovsky white) and wheat (variety Sonora) were cultivated during the lunar light-dark cycle (i. e. 15 day light: 15 day dark). The experiments demonstrated that traditional plant products can be obtained under the conditions of lunar photoperiod. Grain of wheat grown during the lunar photoperiod were tested as seed material for further cultivation under similar conditions."}
{"id": "PMID:26831", "title": "The effect of phospholipase D on the function of fragmented sarcoplasmic reticulum.", "content": "Incubations of fresh preparations of fragmented sarcoplasmic reticulum (FSR) were carried out at pH 5.7. This pH was necessary for hydrolysis of phospholipids by phospholipase D. The pH did not influence calcium uptake or the activity of calcium-stimulated ATPase of FSR. Treatment of FSR with phospholipase D caused hydrolysis of the membrane phospholipids. The phosphatidic acid produced remained bound to the membrane. Increasing phospholipid cleavage was paralleled by loss of calcium uptake, which was complete when about two-thirds of the membrane phospholipids were hydrolyzed.", "contents": "The effect of phospholipase D on the function of fragmented sarcoplasmic reticulum. Incubations of fresh preparations of fragmented sarcoplasmic reticulum (FSR) were carried out at pH 5.7. This pH was necessary for hydrolysis of phospholipids by phospholipase D. The pH did not influence calcium uptake or the activity of calcium-stimulated ATPase of FSR. Treatment of FSR with phospholipase D caused hydrolysis of the membrane phospholipids. The phosphatidic acid produced remained bound to the membrane. Increasing phospholipid cleavage was paralleled by loss of calcium uptake, which was complete when about two-thirds of the membrane phospholipids were hydrolyzed."}
{"id": "PMID:26832", "title": "Multiple forms of acid phosphatase activity in Gaucher's disease.", "content": "Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to those of the major acid phosphatase activity observed to be present in serum of patients with Gaucher's disease. These data indicate that simple spleen spillage cannot account for the increased levels of serum acid phosphatase in patients with Gaucher's disease.", "contents": "Multiple forms of acid phosphatase activity in Gaucher's disease. Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to those of the major acid phosphatase activity observed to be present in serum of patients with Gaucher's disease. These data indicate that simple spleen spillage cannot account for the increased levels of serum acid phosphatase in patients with Gaucher's disease."}
{"id": "PMID:26851", "title": "[Thermostability of glutamine synthetase in Candida tropicalis feed yeasts in Mg-, Mn- and Co-activated systems].", "content": "The thermostability of glutamine synthetase of Candida tropicalis was studied in systems activated by Mg, Mn and Co. The enzyme was found to be very thermolabile. Its thermostability depended on the nature of a bivalent cation used in the reaction mixture. Metals stabilized the enzyme since preincubation with metal cations increased the thermostability of glutamine synthetase. Purification of the enzyme preparation increased the stabilizing action of bivalent cations (Mg2+, Mn2+, Co2+).", "contents": "[Thermostability of glutamine synthetase in Candida tropicalis feed yeasts in Mg-, Mn- and Co-activated systems]. The thermostability of glutamine synthetase of Candida tropicalis was studied in systems activated by Mg, Mn and Co. The enzyme was found to be very thermolabile. Its thermostability depended on the nature of a bivalent cation used in the reaction mixture. Metals stabilized the enzyme since preincubation with metal cations increased the thermostability of glutamine synthetase. Purification of the enzyme preparation increased the stabilizing action of bivalent cations (Mg2+, Mn2+, Co2+)."}
{"id": "PMID:26852", "title": "[Effect of the composition of the medium and the conditions of Aspergillus foetidus cultivation on the biosynthesis of glucoamylase].", "content": "The optimal conditions for biosynthesis of exocellular glucoamylase were found in the course of submerged cultivation of Aspergillus foetidus ATCC 14916: pH 4.5 at the beginning of cultivation, cultivation for four days, a temperature of 30 degrees C, and an aeration in the fermenter of 1.5 volumes of the air per 1 volume of the medium with a stirring of 280 rpm. The material can be inoculated either as spores (1 X 10(7) spores per 100 ml of the medium) or a material germinated from spores (5% by volume). The composition of the medium was improved by using waste products of the agricultural industry (wheat and rice bran, yellow maize, etc.). The maximum biosynthesis of glucoamylase under the optimum conditions of cultivation was observed on crushed yellow maize (10--15%): up to 6.8--8.0 units of GIA (g of glucose per hour) per 1 ml of the cultural filtrate which was 3.4--4.0 times higher than on the original medium and 5--10 times higher than for Endomycopsis bispora, Endomycopsis sp. 20--9, Aspergillus niger and other cultures producing glucoamylase.", "contents": "[Effect of the composition of the medium and the conditions of Aspergillus foetidus cultivation on the biosynthesis of glucoamylase]. The optimal conditions for biosynthesis of exocellular glucoamylase were found in the course of submerged cultivation of Aspergillus foetidus ATCC 14916: pH 4.5 at the beginning of cultivation, cultivation for four days, a temperature of 30 degrees C, and an aeration in the fermenter of 1.5 volumes of the air per 1 volume of the medium with a stirring of 280 rpm. The material can be inoculated either as spores (1 X 10(7) spores per 100 ml of the medium) or a material germinated from spores (5% by volume). The composition of the medium was improved by using waste products of the agricultural industry (wheat and rice bran, yellow maize, etc.). The maximum biosynthesis of glucoamylase under the optimum conditions of cultivation was observed on crushed yellow maize (10--15%): up to 6.8--8.0 units of GIA (g of glucose per hour) per 1 ml of the cultural filtrate which was 3.4--4.0 times higher than on the original medium and 5--10 times higher than for Endomycopsis bispora, Endomycopsis sp. 20--9, Aspergillus niger and other cultures producing glucoamylase."}
{"id": "PMID:26853", "title": "[Cellulase formation by soil yeasts of the genus Trichosporon and by microscopic fungi].", "content": "The production of celulases by a soil yeast belonging to the genus Trichosporon and by microscopic fungi of various systematic groups was studied. The yeast synthesized relatively small amounts of cellulases in contrast to microscopic fungi. The active culture producing cellulases was the fungus Trichoderma longibrachiatum 7-26.", "contents": "[Cellulase formation by soil yeasts of the genus Trichosporon and by microscopic fungi]. The production of celulases by a soil yeast belonging to the genus Trichosporon and by microscopic fungi of various systematic groups was studied. The yeast synthesized relatively small amounts of cellulases in contrast to microscopic fungi. The active culture producing cellulases was the fungus Trichoderma longibrachiatum 7-26."}
{"id": "PMID:26855", "title": "[Cultivation of feed yeasts on media with carbohydrates].", "content": "The different culture of yeasts oxidizing hydrocarbons and the accompanying microflora are, under certain physico-chemical conditions, in metabiotic relationships which provide stability of the system. These relationships were studied with yeast cultures belonging to the Candida genus and oxidizing hydrocarbons. The relationships between the hydrocarbon oxidizing yeast Candida guilliermondii and other species of the genus Candida were determined by a combination of active and passive antogonism, as the result of which strains of this species completely dominated in the cenosis of fermenters.", "contents": "[Cultivation of feed yeasts on media with carbohydrates]. The different culture of yeasts oxidizing hydrocarbons and the accompanying microflora are, under certain physico-chemical conditions, in metabiotic relationships which provide stability of the system. These relationships were studied with yeast cultures belonging to the Candida genus and oxidizing hydrocarbons. The relationships between the hydrocarbon oxidizing yeast Candida guilliermondii and other species of the genus Candida were determined by a combination of active and passive antogonism, as the result of which strains of this species completely dominated in the cenosis of fermenters."}
{"id": "PMID:26856", "title": "[Origin of adifferentiated variants of Streptomyces roseoflavus in submerged culture].", "content": "Adifferentiated Nocardia-like variants (Nv) of Streptomyces roseoflavus var. roseofungini, similar in their cultural characteristics with the variant 1-68 described elsewhere (Nikitina, 1968; Kalakoutskii a. Nikitina, 1976), can be obtained not only in the course of growth of the parent culture on a solid medium containing fructose in the form of secondary colonies, but also during submerged cultivation with stirring. Interruptions in aeration do not affect accumulation of the cells of such variants in the medium. A direct correlation has been established between the amount of biomass and the number of Nv colonies when submerged mycelium is inoculated into a solid medium.", "contents": "[Origin of adifferentiated variants of Streptomyces roseoflavus in submerged culture]. Adifferentiated Nocardia-like variants (Nv) of Streptomyces roseoflavus var. roseofungini, similar in their cultural characteristics with the variant 1-68 described elsewhere (Nikitina, 1968; Kalakoutskii a. Nikitina, 1976), can be obtained not only in the course of growth of the parent culture on a solid medium containing fructose in the form of secondary colonies, but also during submerged cultivation with stirring. Interruptions in aeration do not affect accumulation of the cells of such variants in the medium. A direct correlation has been established between the amount of biomass and the number of Nv colonies when submerged mycelium is inoculated into a solid medium."}
{"id": "PMID:26857", "title": "[Effectiveness of strains of clover nodule bacteria adapted to the acid reaction of the soil].", "content": "The effectiveness and virulence of clover nodule bacterial strains of different origin was studied as they were adapted to acid pH (4.8) of soil in the course of seven years. In spite of their ecological adaptation (strains from acid and neutral soils), the majority of strains (10 among 20) grew well enough upon numerous transfers onto acid media under new conditions. However, only some adapted strains were more effective, than non-adapted ones on acid soil Storage of the strains on acid media for a prolonged time had a positive effect on their virulence, when clover was inoculated on calcareous soil.", "contents": "[Effectiveness of strains of clover nodule bacteria adapted to the acid reaction of the soil]. The effectiveness and virulence of clover nodule bacterial strains of different origin was studied as they were adapted to acid pH (4.8) of soil in the course of seven years. In spite of their ecological adaptation (strains from acid and neutral soils), the majority of strains (10 among 20) grew well enough upon numerous transfers onto acid media under new conditions. However, only some adapted strains were more effective, than non-adapted ones on acid soil Storage of the strains on acid media for a prolonged time had a positive effect on their virulence, when clover was inoculated on calcareous soil."}
{"id": "PMID:26863", "title": "Isoenzymes of human liver alpha-L-fucosidase: chemical relationship, kinetic studies, and immunochemical characterization.", "content": "The chemical relationship of the seven forms of human liver alpha-L fucosidase has been studied by isoelectric focusing of neuraminidase- and sialytransferase-treated preparations of alpha-L-fucosidase. Neuraminidase treatment leads to a decrease in the activity of the more acidic forms (IV-VII) and a concimitant increase in the activity of the more neutral forms (I-II). Incubation of the neuraminidase-treated fucosidase (forms I-III) with radiolabelled cytidine monophosphate-N-3H-acetylneuraminic acid and an enriched preparation of sialytransferase devoid of fucosidase activity led to regeneration of the more acidic fucosidase isoenzymes (IV-VII) with the same isoelectric points and in nearly the same proportion as before neuraminidase treatment. These experiments suggest that the isoenzymes of human liver alpha-L-fucosidase are related, at least in part, by sialic acid residues. The seven isoenzymes of purified human liver alpha-L-fucosidase have been separated by preparative isoelectric focusing and characterized kinetically and immunochemically. Differences in Michaelis constants (Km's) and pH optimum curves were found for some of the isoenzymes. All seven isoenzymes were immunoprecipitated using the IgG fraction of anti-alpha-L-fucosidase antiserum suggesting that the presence of sialic acid residues does not affect the antigenicity of the forms of alpha-L-fucosidase.", "contents": "Isoenzymes of human liver alpha-L-fucosidase: chemical relationship, kinetic studies, and immunochemical characterization. The chemical relationship of the seven forms of human liver alpha-L fucosidase has been studied by isoelectric focusing of neuraminidase- and sialytransferase-treated preparations of alpha-L-fucosidase. Neuraminidase treatment leads to a decrease in the activity of the more acidic forms (IV-VII) and a concimitant increase in the activity of the more neutral forms (I-II). Incubation of the neuraminidase-treated fucosidase (forms I-III) with radiolabelled cytidine monophosphate-N-3H-acetylneuraminic acid and an enriched preparation of sialytransferase devoid of fucosidase activity led to regeneration of the more acidic fucosidase isoenzymes (IV-VII) with the same isoelectric points and in nearly the same proportion as before neuraminidase treatment. These experiments suggest that the isoenzymes of human liver alpha-L-fucosidase are related, at least in part, by sialic acid residues. The seven isoenzymes of purified human liver alpha-L-fucosidase have been separated by preparative isoelectric focusing and characterized kinetically and immunochemically. Differences in Michaelis constants (Km's) and pH optimum curves were found for some of the isoenzymes. All seven isoenzymes were immunoprecipitated using the IgG fraction of anti-alpha-L-fucosidase antiserum suggesting that the presence of sialic acid residues does not affect the antigenicity of the forms of alpha-L-fucosidase."}
{"id": "PMID:26866", "title": "[On the pharmacological treatment of acute spasmodic laryngitis (Pseudo-Croup) (author's transl)].", "content": "Three aspects of the pharmacological treatment of pseudo-croup are discussed in this article. Sedatives should be given only when close clinical supervision is guaranteed. Otherwise the apparent drowsiness observed in patients passing from stage III to stage IV of the disease may be masked or misinterpreted due to these sedatives. Emetics used occasionally in the USA, and also frequently administered in Europe to the turn of the present century, are no longer used for treatment in Germany. There are no controlled studies showing their effectiveness. In contrast to the common practice in Germany, glucocorticosteroids are less frequently used in the USA. Theoretical considerations suggest their usefulness, but to data there is still no convincing proof of their clinical effectiveness.", "contents": "[On the pharmacological treatment of acute spasmodic laryngitis (Pseudo-Croup) (author's transl)]. Three aspects of the pharmacological treatment of pseudo-croup are discussed in this article. Sedatives should be given only when close clinical supervision is guaranteed. Otherwise the apparent drowsiness observed in patients passing from stage III to stage IV of the disease may be masked or misinterpreted due to these sedatives. Emetics used occasionally in the USA, and also frequently administered in Europe to the turn of the present century, are no longer used for treatment in Germany. There are no controlled studies showing their effectiveness. In contrast to the common practice in Germany, glucocorticosteroids are less frequently used in the USA. Theoretical considerations suggest their usefulness, but to data there is still no convincing proof of their clinical effectiveness."}
{"id": "PMID:26867", "title": "[Atrial tachycardia with atrio-ventricular block in infancy and childhood (author's transl)].", "content": "Atrial tachycardia with atrio-ventricular block is a very rare arrhythmia in infancy and childhood. We saw ten patients between 3 days and fifteen years old. Six of them had a congenital heart disease, in four cases we could'nt find any cardiac or extracardiac illness. In every case digitalis intoxication was excluded. Clinical findings, electrocardiographic features, therapy and prognosis are reported.", "contents": "[Atrial tachycardia with atrio-ventricular block in infancy and childhood (author's transl)]. Atrial tachycardia with atrio-ventricular block is a very rare arrhythmia in infancy and childhood. We saw ten patients between 3 days and fifteen years old. Six of them had a congenital heart disease, in four cases we could'nt find any cardiac or extracardiac illness. In every case digitalis intoxication was excluded. Clinical findings, electrocardiographic features, therapy and prognosis are reported."}
{"id": "PMID:26865", "title": "[Electrical conductivity of isoionic DNA solutions].", "content": "Conductance of the DNA isoionic solutions obtained from aqueous solutions of its sodium salt using a column with mixed bed ionexchangers has been investigated. It has been found that in Kohlrausch's plots equivalent conductance slightly decreased with polymer concentration. Comparison of the degree of ionization (alpha) calculated from conductance measurements with those calculated from experimental pH values of isoionic solutions at different polymer concentrations revealed that the mobility of dissociating counterations decreases significantly under the influence of the electrostatic potential of the macroion.", "contents": "[Electrical conductivity of isoionic DNA solutions]. Conductance of the DNA isoionic solutions obtained from aqueous solutions of its sodium salt using a column with mixed bed ionexchangers has been investigated. It has been found that in Kohlrausch's plots equivalent conductance slightly decreased with polymer concentration. Comparison of the degree of ionization (alpha) calculated from conductance measurements with those calculated from experimental pH values of isoionic solutions at different polymer concentrations revealed that the mobility of dissociating counterations decreases significantly under the influence of the electrostatic potential of the macroion."}
{"id": "PMID:26870", "title": "[Treatment of hypertension with a combination of pyridopyridazine derivative with a beta-receptor blocker. Studies on the hemodynamic course (author's transl)].", "content": "22 pateints with a fixed, sometimes therapy-resistant (N = 18) hypertension were treated with a new antihypertensive agent, the pyridopyridazine derivative BQ 22-708 and hemodynamically investigated. 14 hypertensives received single oral doses of between 5 and 15 mg, 8 other patients also received additional treatment with a beta-receptor blocker (0.8 mg pindolol i.v.) or calcium antagonist (10 mg verapamil i.v.). In hypertension which is only poorly controllable or resistant, therapy with BQ 22-708 combined with beta-receptor offers a genuine alternative medication.", "contents": "[Treatment of hypertension with a combination of pyridopyridazine derivative with a beta-receptor blocker. Studies on the hemodynamic course (author's transl)]. 22 pateints with a fixed, sometimes therapy-resistant (N = 18) hypertension were treated with a new antihypertensive agent, the pyridopyridazine derivative BQ 22-708 and hemodynamically investigated. 14 hypertensives received single oral doses of between 5 and 15 mg, 8 other patients also received additional treatment with a beta-receptor blocker (0.8 mg pindolol i.v.) or calcium antagonist (10 mg verapamil i.v.). In hypertension which is only poorly controllable or resistant, therapy with BQ 22-708 combined with beta-receptor offers a genuine alternative medication."}
{"id": "PMID:26871", "title": "[Cardiac neurosis in everyday general medical practice (author's transl)].", "content": "From results of the study of 37 patients with cardiac neurosis, new conceptual relationships to explain this condition are developed. Cardiac neurosis is explained as a disturbance of the \"psycho-neurovegetative self-regulation mechanism\" (servomechanisms). The authors show how such a conception, which has been borrowed from the servomechanism technique, may favourably influence the diagnosis and therapy of this condition. It has been tried in that way to link the two opposites: organic and functional causes. Some therapeutic approaches adapted to the structure of everyday general medical practice are suggested.", "contents": "[Cardiac neurosis in everyday general medical practice (author's transl)]. From results of the study of 37 patients with cardiac neurosis, new conceptual relationships to explain this condition are developed. Cardiac neurosis is explained as a disturbance of the \"psycho-neurovegetative self-regulation mechanism\" (servomechanisms). The authors show how such a conception, which has been borrowed from the servomechanism technique, may favourably influence the diagnosis and therapy of this condition. It has been tried in that way to link the two opposites: organic and functional causes. Some therapeutic approaches adapted to the structure of everyday general medical practice are suggested."}
{"id": "PMID:26872", "title": "Variable content of histaminase, L-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung. Biologic and clinical implications.", "content": "To ascertain whether the content of endocrine markers is constant in small-cell carcinoma of the lung, levels of three markers of medullary thyroid carcinoma were studied in this tumor. Histaminase was increased in six of six primary tumors (three to 14,000 times), L-dopa decarboxylase in four of six (six to 30 times), and calcitonin in one of one (eight times) over levels in adjacent lung. Marker levels in mediastinal metastases reflected those in primary tumors in four of five patients. However, in four of seven, multiple hepatic metastases contained low to absent levels despite simultaneously high values in chest lesions. Immunohistochemical studies of histaminase revealed that within each primary tumor different cells contained different amounts of the enzyme. Since marker content varied between tumor cells, between primary tumors and between metastases in individual patients we conclude that circulating levels of these three markers cannot be expected necessarily to mirror tumor burden in patients with small-cell lung tumors.", "contents": "Variable content of histaminase, L-dopa decarboxylase and calcitonin in small-cell carcinoma of the lung. Biologic and clinical implications. To ascertain whether the content of endocrine markers is constant in small-cell carcinoma of the lung, levels of three markers of medullary thyroid carcinoma were studied in this tumor. Histaminase was increased in six of six primary tumors (three to 14,000 times), L-dopa decarboxylase in four of six (six to 30 times), and calcitonin in one of one (eight times) over levels in adjacent lung. Marker levels in mediastinal metastases reflected those in primary tumors in four of five patients. However, in four of seven, multiple hepatic metastases contained low to absent levels despite simultaneously high values in chest lesions. Immunohistochemical studies of histaminase revealed that within each primary tumor different cells contained different amounts of the enzyme. Since marker content varied between tumor cells, between primary tumors and between metastases in individual patients we conclude that circulating levels of these three markers cannot be expected necessarily to mirror tumor burden in patients with small-cell lung tumors."}
{"id": "PMID:26878", "title": "Current problems in the control of mosquitoes.", "content": "Since the incidence of mosquito-borne disease was drastically reduced by the use of DDT in the 1950s, the problem has again worsened and no single method of eradication seems likely to achieve lasting success. It now seems that the best hope lies in the combination of various methods of chemical control and perhaps genetic control to rid the Third World of its most important disease sector.", "contents": "Current problems in the control of mosquitoes. Since the incidence of mosquito-borne disease was drastically reduced by the use of DDT in the 1950s, the problem has again worsened and no single method of eradication seems likely to achieve lasting success. It now seems that the best hope lies in the combination of various methods of chemical control and perhaps genetic control to rid the Third World of its most important disease sector."}
{"id": "PMID:26888", "title": "[Value of brain metabolic studies in post-traumatic coma].", "content": "In 34 comatose patients in the acute phase, the mean hemispheric CBF is lowered as well as the CMRO2, with a quite good relation between these values and the coma level and prognostic so. The cerebral response to a PaCO2 range indicates a quite good relation with the coma level (the lowest value in the most severe comas). The cerebral autoregulation study, using Aramine induced hypertension, can separate the cases with a present autoregulation and the cases with a loss of autoregulation (the most severe and the poorest prognosis). In dynamic conditions (variation of the PaCO2 or Aramine induced hypertension), the change in CMRO2 is interesting : rather good prognosis among the patients with a normal metabolic autoregulation - poor prognosis among those whose metabolic autoregulation is lost.", "contents": "[Value of brain metabolic studies in post-traumatic coma]. In 34 comatose patients in the acute phase, the mean hemispheric CBF is lowered as well as the CMRO2, with a quite good relation between these values and the coma level and prognostic so. The cerebral response to a PaCO2 range indicates a quite good relation with the coma level (the lowest value in the most severe comas). The cerebral autoregulation study, using Aramine induced hypertension, can separate the cases with a present autoregulation and the cases with a loss of autoregulation (the most severe and the poorest prognosis). In dynamic conditions (variation of the PaCO2 or Aramine induced hypertension), the change in CMRO2 is interesting : rather good prognosis among the patients with a normal metabolic autoregulation - poor prognosis among those whose metabolic autoregulation is lost."}
{"id": "PMID:26891", "title": "[Alkaline urine in the aged].", "content": "Considering the frequent finding of alkalinity in the urines of elderly people of both sexes, we can propose many hypothesis among which the most probable seems a latent renal failure with secondary hyperparathyroidism and consequent alkalinization of the urines. We can presume that such a frequent alkalinity of the urines in old subjects has an important role in the frequent infectious of the urinary tract of elderly people.", "contents": "[Alkaline urine in the aged]. Considering the frequent finding of alkalinity in the urines of elderly people of both sexes, we can propose many hypothesis among which the most probable seems a latent renal failure with secondary hyperparathyroidism and consequent alkalinization of the urines. We can presume that such a frequent alkalinity of the urines in old subjects has an important role in the frequent infectious of the urinary tract of elderly people."}
{"id": "PMID:26893", "title": "[Hemodynamic effects of antihypertensive drugs].", "content": "The physiopathology of hypertension is not fully understood, though the haemodynamic pictures accompanying the various arterial forms have been established. Clinical employment of antihypertensive drugs should tend to correct these pictures and the extent to which this is true is examined in the light of the latest evidence with respect to the drugs most commonly used.", "contents": "[Hemodynamic effects of antihypertensive drugs]. The physiopathology of hypertension is not fully understood, though the haemodynamic pictures accompanying the various arterial forms have been established. Clinical employment of antihypertensive drugs should tend to correct these pictures and the extent to which this is true is examined in the light of the latest evidence with respect to the drugs most commonly used."}
{"id": "PMID:26895", "title": "Urinary sulfate excretion in children with classic renal tubular acidosis.", "content": "These studies quantitat the significantly elevated sulfate excretion in the urine of children with classic renal tubular acidosis as compared to six weight-matched controls (1.4 +/-0.5 vs. 0.7 +/- 0.2 mEq/kg/day;p less than 0.05). This sulfate loss may result in a subclinical sulfate deficiency which may contribute to a chondroitin sulfate metabolic disorder.,and thus contribute to the growth failure in children with real tubular acidosis. Futhermore, elevated urinary sulfate excretion may be an early diagnostic finding in infancy prior to the manifestation of renal acidification defects. It is not known whether the sulfate loss is related to a primary renal tubular defect or secondary to metabolic acidosis, although the increased sulfate excretion persisting after correction of metabolic acidosis would tend to suggest a primary defect. However, the normal plasma sulfate concentration and the relatively short period of study permit no definitive answer at this time.", "contents": "Urinary sulfate excretion in children with classic renal tubular acidosis. These studies quantitat the significantly elevated sulfate excretion in the urine of children with classic renal tubular acidosis as compared to six weight-matched controls (1.4 +/-0.5 vs. 0.7 +/- 0.2 mEq/kg/day;p less than 0.05). This sulfate loss may result in a subclinical sulfate deficiency which may contribute to a chondroitin sulfate metabolic disorder.,and thus contribute to the growth failure in children with real tubular acidosis. Futhermore, elevated urinary sulfate excretion may be an early diagnostic finding in infancy prior to the manifestation of renal acidification defects. It is not known whether the sulfate loss is related to a primary renal tubular defect or secondary to metabolic acidosis, although the increased sulfate excretion persisting after correction of metabolic acidosis would tend to suggest a primary defect. However, the normal plasma sulfate concentration and the relatively short period of study permit no definitive answer at this time."}
{"id": "PMID:26896", "title": "Hydrogen ion production secondary to metabolism of sulfur-amino acids and organic acids.", "content": "The rate of acid production in infants and young children was quoted to be 1-2 mEq/kg/day but in fact, the sole reference used in all these instances did not permit such quantitation. In order to evaluate the rate of endogenous acid production, we applied the quantitative technique of Lennon et al. in the following normal subjects, where column A represents hydrogen ion released from metabolism of sulfur-containing amion acids; column B represents hydrogen ion released from incomplete oxidation of organic acids; the sum A and B gives an estimation of endogenous net acid production (NAP).", "contents": "Hydrogen ion production secondary to metabolism of sulfur-amino acids and organic acids. The rate of acid production in infants and young children was quoted to be 1-2 mEq/kg/day but in fact, the sole reference used in all these instances did not permit such quantitation. In order to evaluate the rate of endogenous acid production, we applied the quantitative technique of Lennon et al. in the following normal subjects, where column A represents hydrogen ion released from metabolism of sulfur-containing amion acids; column B represents hydrogen ion released from incomplete oxidation of organic acids; the sum A and B gives an estimation of endogenous net acid production (NAP)."}
{"id": "PMID:26899", "title": "The effect of atropine on the lower esophageal sphincter in late pregnancy.", "content": "Intraluminal gastroesophageal pressure and pH studies have been performed on 8 nonpregnant women, 10 pregnant women with heartburn, and 10 pregnant women without heartburn. Each patient was tested under resting conditions and after intravenous injection of 0.6 mg atropine. In both groups of pregnant patients the intragastric pressure was found to be higher than that of the nonpregnant subjects. The stomach to lower esophageal sphincter pressure (LESP) gradient under resting conditions was least in the pregnant patients with heartburn. After the administration of atropine, a fall in the LESP occurred in all 3 groups of patients which was most profound in the nonpregnant subjects and in the pregnant patients without heartburn. These changes and the pH recordings of the lower esophagus indicate the adverse effect that atropine has on the competency of the LESP both in pregnancy and in the nonpregnant state. Atropine should therefore be used with caution as a premedicant and preferably combined with metoclopramide (Maxolon).", "contents": "The effect of atropine on the lower esophageal sphincter in late pregnancy. Intraluminal gastroesophageal pressure and pH studies have been performed on 8 nonpregnant women, 10 pregnant women with heartburn, and 10 pregnant women without heartburn. Each patient was tested under resting conditions and after intravenous injection of 0.6 mg atropine. In both groups of pregnant patients the intragastric pressure was found to be higher than that of the nonpregnant subjects. The stomach to lower esophageal sphincter pressure (LESP) gradient under resting conditions was least in the pregnant patients with heartburn. After the administration of atropine, a fall in the LESP occurred in all 3 groups of patients which was most profound in the nonpregnant subjects and in the pregnant patients without heartburn. These changes and the pH recordings of the lower esophagus indicate the adverse effect that atropine has on the competency of the LESP both in pregnancy and in the nonpregnant state. Atropine should therefore be used with caution as a premedicant and preferably combined with metoclopramide (Maxolon)."}
{"id": "PMID:26900", "title": "Deceleration/contraction ratios as an index of fetal health during labor.", "content": "Internal FHR tracings of 259 patients with variable decelerations and 49 with late decelerations were analyzed for frequency and severity of the pattern in an attempt to correlate with fetal pH or Apgar score at 1 minute. A significant increase in the risk of fetal acidosis was associated with a frequency of greater than 30% variable decelerations and 20% late decelerations. It also increased with the increase of severity of the pattern. Variable decelerations are not good predictors of Apgar scores less than or equal to 6 at 1 minute, but late decelerations are predictive when they occur more than 20% of the time. The fetus with variable decelerations a normal pH can be observed through the first stage of labor with a high degree of confidence. However, when a 20% or more moderate-to-severe late deceleration/contraction ratio is present, intervention is necessary even if scalp blood pH is normal. The FHR deceleration/uterine contraction (UC) ratio is a simple bedside technique for assessing fetal outcome.", "contents": "Deceleration/contraction ratios as an index of fetal health during labor. Internal FHR tracings of 259 patients with variable decelerations and 49 with late decelerations were analyzed for frequency and severity of the pattern in an attempt to correlate with fetal pH or Apgar score at 1 minute. A significant increase in the risk of fetal acidosis was associated with a frequency of greater than 30% variable decelerations and 20% late decelerations. It also increased with the increase of severity of the pattern. Variable decelerations are not good predictors of Apgar scores less than or equal to 6 at 1 minute, but late decelerations are predictive when they occur more than 20% of the time. The fetus with variable decelerations a normal pH can be observed through the first stage of labor with a high degree of confidence. However, when a 20% or more moderate-to-severe late deceleration/contraction ratio is present, intervention is necessary even if scalp blood pH is normal. The FHR deceleration/uterine contraction (UC) ratio is a simple bedside technique for assessing fetal outcome."}
{"id": "PMID:26901", "title": "gamma-Glutamyl transpeptidase activity in sheep serum: normal values and an evaluation of its potential for detecting liver involvement in experimental lupinosis.", "content": "A brief survey of the literature on gamma-glutamyl transpeptidase (gamma-GT) activity is included in this study. The levels of activity in the serum of normal Merino sheep (13,6-32,4 mI.U/ml) were ascertained as a preliminary to following the activity through the entire course of experimentally induced ovine lupinosis, a hepatotoxicosis caused by Phomopsis leptostromiformis (K\u00fchn) Bub\u00e1k. The response of the serum level of gamma-GT activity to the course of the disease was compared with that of glutamate oxaloacetic transaminase (GOT) and 2 liver function tests for the purpose of assessing its potential application in the study of this mycotoxicosis. Because the levels of activity of gamma-GT were more valuable for the early diagnosis of low grade acute intoxication and the detection of chronic liver involvement while those of GOT gave better information on the development of severe acute hepato-cellular damage, these 2 enzymes, considered together, were found to give the best information on the course of the toxicosis. The changes in gamma-GT activity during various stages of intoxication were also related to the histopathological lesions in the liver.", "contents": "gamma-Glutamyl transpeptidase activity in sheep serum: normal values and an evaluation of its potential for detecting liver involvement in experimental lupinosis. A brief survey of the literature on gamma-glutamyl transpeptidase (gamma-GT) activity is included in this study. The levels of activity in the serum of normal Merino sheep (13,6-32,4 mI.U/ml) were ascertained as a preliminary to following the activity through the entire course of experimentally induced ovine lupinosis, a hepatotoxicosis caused by Phomopsis leptostromiformis (K\u00fchn) Bub\u00e1k. The response of the serum level of gamma-GT activity to the course of the disease was compared with that of glutamate oxaloacetic transaminase (GOT) and 2 liver function tests for the purpose of assessing its potential application in the study of this mycotoxicosis. Because the levels of activity of gamma-GT were more valuable for the early diagnosis of low grade acute intoxication and the detection of chronic liver involvement while those of GOT gave better information on the development of severe acute hepato-cellular damage, these 2 enzymes, considered together, were found to give the best information on the course of the toxicosis. The changes in gamma-GT activity during various stages of intoxication were also related to the histopathological lesions in the liver."}
{"id": "PMID:26902", "title": "The metabolic profile of adult Fasciola hepatica obtained from rafoxanide-treated sheep.", "content": "Sheep infected with adult Fasciola hepatica were drenched with rafoxanide. At 4, 8, 16 and 24 h after drenching the sheep were killed and the flukes removed, washed and rapidly frozen in liquid nitrogen. The content of key metabolites in the fermentation pathway were determined and compared with those in control F. hepatica, whose hosts were not treated with rafoxanide. Rafoxanide decreased glycogen, malate, NADH and ATP levels. The level of other metabolites in the pathway increased for the first 8-16 h after rafoxanide treatment. The marked decrease in ATP and glycogen, and the increase in total [NAD+]/[NADH] and [oxaloacetate]/[malate], together with the changed content of other metabolites, led to the conclusion that the mode of action of rafoxanide against F. hepatica in vivo is by uncoupling oxidative phosphorylation.", "contents": "The metabolic profile of adult Fasciola hepatica obtained from rafoxanide-treated sheep. Sheep infected with adult Fasciola hepatica were drenched with rafoxanide. At 4, 8, 16 and 24 h after drenching the sheep were killed and the flukes removed, washed and rapidly frozen in liquid nitrogen. The content of key metabolites in the fermentation pathway were determined and compared with those in control F. hepatica, whose hosts were not treated with rafoxanide. Rafoxanide decreased glycogen, malate, NADH and ATP levels. The level of other metabolites in the pathway increased for the first 8-16 h after rafoxanide treatment. The marked decrease in ATP and glycogen, and the increase in total [NAD+]/[NADH] and [oxaloacetate]/[malate], together with the changed content of other metabolites, led to the conclusion that the mode of action of rafoxanide against F. hepatica in vivo is by uncoupling oxidative phosphorylation."}
{"id": "PMID:26908", "title": "A basis for migraine therapy- the autonomic theory reappraised.", "content": "The concept that migraine results from an initial vasoconstriction due to increased release of noradrenaline from the sympathetic nerves to cranial blood vessels has been reappraised in the light of recently acquired knowledge of the mechanisms of action of drugs used in the treatment of migraine, physiological and pharmacological evidence implicating noradrenaline, and the observations by others that several migraine variants may be associated with some degree of sympathetic overactivity. If the theory is correct, it suggests that both prophylaxis and management of the acute condition should be possible by means of selective alpha-adrenoceptor antagonism. The use of drugs with potentially dangerous vasoconstrictor properties appears to be unnecessary. The suggestion is made that the increased adrenergic activity might result from changes within the hypothalamus.", "contents": "A basis for migraine therapy- the autonomic theory reappraised. The concept that migraine results from an initial vasoconstriction due to increased release of noradrenaline from the sympathetic nerves to cranial blood vessels has been reappraised in the light of recently acquired knowledge of the mechanisms of action of drugs used in the treatment of migraine, physiological and pharmacological evidence implicating noradrenaline, and the observations by others that several migraine variants may be associated with some degree of sympathetic overactivity. If the theory is correct, it suggests that both prophylaxis and management of the acute condition should be possible by means of selective alpha-adrenoceptor antagonism. The use of drugs with potentially dangerous vasoconstrictor properties appears to be unnecessary. The suggestion is made that the increased adrenergic activity might result from changes within the hypothalamus."}
{"id": "PMID:26910", "title": "[Changes in the urinary excretion of gamma-glutamyltranspeptidase, leucine aminopeptidas and alkaline phosphatase in the combined action of ethylene glycol and high temperature].", "content": "Gamma-glutamyl transpeptidase (gamma--GTP), leucine aminopeptidase (LAP) and alkaline phosphatase (AP) excretion in rats is followed in dynamics (2, 8, 15, 30 and 90 days) upon isolated and combined treatment with ethylene glycol (EG) at dose 1/8 LD50 and temperature of the environment 35 degrees C. Under the effect of high temperature an increase in the excretion of enzymes in the early observation terms is noted. The independent application of the noxa causes a reduction in gamma--GTR and LAP excretion, and an increase in AP. The temperature factor attenuates the toxic effect of EG relative to the enzymes under study at the end of the observation period. Changes in gamma--GTP excretion are considered as the earliest and most sensitive sign of tubular lesions.", "contents": "[Changes in the urinary excretion of gamma-glutamyltranspeptidase, leucine aminopeptidas and alkaline phosphatase in the combined action of ethylene glycol and high temperature]. Gamma-glutamyl transpeptidase (gamma--GTP), leucine aminopeptidase (LAP) and alkaline phosphatase (AP) excretion in rats is followed in dynamics (2, 8, 15, 30 and 90 days) upon isolated and combined treatment with ethylene glycol (EG) at dose 1/8 LD50 and temperature of the environment 35 degrees C. Under the effect of high temperature an increase in the excretion of enzymes in the early observation terms is noted. The independent application of the noxa causes a reduction in gamma--GTR and LAP excretion, and an increase in AP. The temperature factor attenuates the toxic effect of EG relative to the enzymes under study at the end of the observation period. Changes in gamma--GTP excretion are considered as the earliest and most sensitive sign of tubular lesions."}
{"id": "PMID:26912", "title": "Mode of action of colicin Ia: effect of colicin on the Escherichia coli proton electrochemical gradient.", "content": "By use of the technique of flow dialysis, the membrane potential (deltapsi) and pH gradient (deltapH) have been measured in colicin Ia-treated Escherichia coli K-12 cells and in membrane vesicles prepared from such cells. Although such cells and vesicles are able to generate a transmembrane deltapH at pH 5.5, they do not generate a transmembrane deltapsi. Glucose-6-phospate uptake by cells is shown to be stimulated at pH 5.5 and inhibited at pH 7.5 by colicin Ia treatment. On the other hand, proline uptake is demonstrated to be inhibited progressively at pH 5.5, 6.6, and 7.5 in colicin Ia-treated cells. These data provide strong evidence for a colicin Ia-induced membrane deplorization and indicate that the membrane becomes permeable to ion(s) other than protons after treatment with colicin Ia.", "contents": "Mode of action of colicin Ia: effect of colicin on the Escherichia coli proton electrochemical gradient. By use of the technique of flow dialysis, the membrane potential (deltapsi) and pH gradient (deltapH) have been measured in colicin Ia-treated Escherichia coli K-12 cells and in membrane vesicles prepared from such cells. Although such cells and vesicles are able to generate a transmembrane deltapH at pH 5.5, they do not generate a transmembrane deltapsi. Glucose-6-phospate uptake by cells is shown to be stimulated at pH 5.5 and inhibited at pH 7.5 by colicin Ia treatment. On the other hand, proline uptake is demonstrated to be inhibited progressively at pH 5.5, 6.6, and 7.5 in colicin Ia-treated cells. These data provide strong evidence for a colicin Ia-induced membrane deplorization and indicate that the membrane becomes permeable to ion(s) other than protons after treatment with colicin Ia."}
{"id": "PMID:26913", "title": "Proposed temperature-dependent conformational transition in D-amino acid oxidase: a differential scanning microcalorimetric study.", "content": "A number of authors have reported observations on D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3.] that they have interpreted in terms of a temperature-dependent conformational transition having a van't Hoff enthalpy amounting to more than 1 cal per g of protein (1 cal = 4.184J). No indication of this transition is obtained by using a differential scanning calorimeter having a sensitivity considerably in excess of that required to detect such a transition. The implications of this discrepancy are discussed.", "contents": "Proposed temperature-dependent conformational transition in D-amino acid oxidase: a differential scanning microcalorimetric study. A number of authors have reported observations on D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3.] that they have interpreted in terms of a temperature-dependent conformational transition having a van't Hoff enthalpy amounting to more than 1 cal per g of protein (1 cal = 4.184J). No indication of this transition is obtained by using a differential scanning calorimeter having a sensitivity considerably in excess of that required to detect such a transition. The implications of this discrepancy are discussed."}
{"id": "PMID:26914", "title": "Elimination of cooperativity in aspartate transcarbamylase by nitration of a single tyrosine residue.", "content": "In a previous report [Landfear, S. M., Lipscomb, W. N. & Evans, D.R. (1978) J. Biol. Chem. 253, 3988--3996] we demonstrated that tetranitromethane can be employed to nitrate a limited number of tyrosine residues in aspartate transcarbamylase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2); such modification eliminates cooperativity, feedback inhibition, and enzymatic activity, and reduces binding of the feedback inhibitor cytidine triphosphate. Cooperativity is lost more rapidly than other properties, and this loss correlates with the nitration of a single tyrosine residue. In this paper, we describe the saturation kinetics of hybrid species constructed from nitrated subunits of one type (either catalytic or regulatory) and native subunits of the other type. We conclude that the modification responsible for loss of cooperativity is on the catalytic subunit. The tryptic peptide containing this modification has been isolated and identified.", "contents": "Elimination of cooperativity in aspartate transcarbamylase by nitration of a single tyrosine residue. In a previous report [Landfear, S. M., Lipscomb, W. N. & Evans, D.R. (1978) J. Biol. Chem. 253, 3988--3996] we demonstrated that tetranitromethane can be employed to nitrate a limited number of tyrosine residues in aspartate transcarbamylase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2); such modification eliminates cooperativity, feedback inhibition, and enzymatic activity, and reduces binding of the feedback inhibitor cytidine triphosphate. Cooperativity is lost more rapidly than other properties, and this loss correlates with the nitration of a single tyrosine residue. In this paper, we describe the saturation kinetics of hybrid species constructed from nitrated subunits of one type (either catalytic or regulatory) and native subunits of the other type. We conclude that the modification responsible for loss of cooperativity is on the catalytic subunit. The tryptic peptide containing this modification has been isolated and identified."}
{"id": "PMID:26915", "title": "Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine.", "content": "A partially purified preparation of the heat-stable enterotoxin of Escherichia coli caused a rapid and persistent increase in electric potential difference and short-circuit current when added in vitro to the luminal surface of isolated rabbit ileal mucosa. As little as 1 ng/ml produced an easily detectable response. Under short-circuit condition, the enterotoxin abolished net Cl- absorption; this change was half that produced by theophylline, which stimulated net secretion. The enterotoxin did not change cyclic AMP concentration but caused large and persistent increases in cyclic GMP concentration. The electrical and nucleotide responses exhibited similar and unusually broad concentration-dependences and maximal effects could not be demonstrated. Theophylline elevated cyclic GMP concentration 3-fold both in the presence and absense of the enterotoxin, suggesting no effect of the toxin on cyclic GMP phosphodiesterase. Guanylate cyclase [GTP pyrophosphatelyase(cyclizing); EC 4.6.1.2] activity in a crude membrane fraction from intestinal epithelial cells was stimulated 7-fold by the enterotoxin. These results suggest that guanylate cyclase stimulation is the basis for the toxin's diarrheagenic effect.", "contents": "Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. A partially purified preparation of the heat-stable enterotoxin of Escherichia coli caused a rapid and persistent increase in electric potential difference and short-circuit current when added in vitro to the luminal surface of isolated rabbit ileal mucosa. As little as 1 ng/ml produced an easily detectable response. Under short-circuit condition, the enterotoxin abolished net Cl- absorption; this change was half that produced by theophylline, which stimulated net secretion. The enterotoxin did not change cyclic AMP concentration but caused large and persistent increases in cyclic GMP concentration. The electrical and nucleotide responses exhibited similar and unusually broad concentration-dependences and maximal effects could not be demonstrated. Theophylline elevated cyclic GMP concentration 3-fold both in the presence and absense of the enterotoxin, suggesting no effect of the toxin on cyclic GMP phosphodiesterase. Guanylate cyclase [GTP pyrophosphatelyase(cyclizing); EC 4.6.1.2] activity in a crude membrane fraction from intestinal epithelial cells was stimulated 7-fold by the enterotoxin. These results suggest that guanylate cyclase stimulation is the basis for the toxin's diarrheagenic effect."}
{"id": "PMID:26916", "title": "Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins.", "content": "Mouse bone marrow and spleen cells were fractionated with the aid of soybean agglutinin and peanut agglutinin. A test for spleen colony-forming units in the isolated fractions showed that the hemopoietic stem cells are agglutinated by both of these lectins. The capacity of the agglutinated fractions to reconstitute lethally irradiated allogeneic mice was investigated. A sequential fractionation of splenocytes from SWR donors by soybean agglutinin and peanut agglutinin, or a single fractionation by soybean agglutinin of splenocytes from BALB/c donors, afforded a cell fraction that successfully reconstituted lethally irradiated (BALB/c X C57BL/6)F1 mice, without complications due to graft-versus-host reaction.", "contents": "Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins. Mouse bone marrow and spleen cells were fractionated with the aid of soybean agglutinin and peanut agglutinin. A test for spleen colony-forming units in the isolated fractions showed that the hemopoietic stem cells are agglutinated by both of these lectins. The capacity of the agglutinated fractions to reconstitute lethally irradiated allogeneic mice was investigated. A sequential fractionation of splenocytes from SWR donors by soybean agglutinin and peanut agglutinin, or a single fractionation by soybean agglutinin of splenocytes from BALB/c donors, afforded a cell fraction that successfully reconstituted lethally irradiated (BALB/c X C57BL/6)F1 mice, without complications due to graft-versus-host reaction."}
{"id": "PMID:26917", "title": "Beneficial and detrimental actions of histamine H1- and H2-receptor antagonists in circulatory shock.", "content": "This study explores the use of both histamine H(1)- and H(2)-receptor antagonists in two different forms of circulatory shock and suggests that histamine may be involved in more than one way in the pathophysiology of circulatory shock. Various single doses of diphenhydramine, chlorpheniramine, promethazine, and burimamide were administered intravenously to Wistar rats subjected to hemorrhagic or bowel ischemia shock. Cumulative survival and mortality, as well as arterial blood pressures and microhematocrits, were monitored. Pretreatment of the animals with the three different H(1)-receptor antagonists exerted significant protection against both forms of shock. Rats pretreated with the H(2)-receptor antagonist, burimamide, demonstrated an exacerbated mortality after induction of shock. Animals pretreated with H(1)-receptor antagonists showed significantly higher mean arterial blood pressure, greater compensatory rebound of blood pressure after induction of shock, and greater responses to transfusion after hemorrhage than control, shocked animals. Similarly, rats pretreated with the H(1)-receptor blockers demonstrated significantly greater compensatory hemodilution which continued late in shock. In marked contrast, rats pretreated with burimamide exhibited opposite effects after hemorrhage and bowel ischemia, i.e., significant falls in blood pressure, lack of compensatory rebound and response to transfusion of shed blood, and a progressive hemoconcentration. This report clearly demonstrates beneficial actions of histamine H(1)-receptor antagonists and detrimental effects of H(2)-receptor antagonists on survival and other parameters in these forms of circulatory shock.", "contents": "Beneficial and detrimental actions of histamine H1- and H2-receptor antagonists in circulatory shock. This study explores the use of both histamine H(1)- and H(2)-receptor antagonists in two different forms of circulatory shock and suggests that histamine may be involved in more than one way in the pathophysiology of circulatory shock. Various single doses of diphenhydramine, chlorpheniramine, promethazine, and burimamide were administered intravenously to Wistar rats subjected to hemorrhagic or bowel ischemia shock. Cumulative survival and mortality, as well as arterial blood pressures and microhematocrits, were monitored. Pretreatment of the animals with the three different H(1)-receptor antagonists exerted significant protection against both forms of shock. Rats pretreated with the H(2)-receptor antagonist, burimamide, demonstrated an exacerbated mortality after induction of shock. Animals pretreated with H(1)-receptor antagonists showed significantly higher mean arterial blood pressure, greater compensatory rebound of blood pressure after induction of shock, and greater responses to transfusion after hemorrhage than control, shocked animals. Similarly, rats pretreated with the H(1)-receptor blockers demonstrated significantly greater compensatory hemodilution which continued late in shock. In marked contrast, rats pretreated with burimamide exhibited opposite effects after hemorrhage and bowel ischemia, i.e., significant falls in blood pressure, lack of compensatory rebound and response to transfusion of shed blood, and a progressive hemoconcentration. This report clearly demonstrates beneficial actions of histamine H(1)-receptor antagonists and detrimental effects of H(2)-receptor antagonists on survival and other parameters in these forms of circulatory shock."}
{"id": "PMID:26918", "title": "Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat.", "content": "Lysyl oxidase catalyzes the crosslinking of collagen and elastin. Lysyl oxidase activity was measured and localized in rat liver during the evolution of hepatic fibrosis induced by CCl4. Enzyme activity measured with DL-[6-3H]-lysine-labeled collagen substrates in liver and plasma increased sharply after approximately 3 wk of injection, reached a maximum at 6 wk, and then decreased. The increase in activity correlated histologically with early connective tissue septa formation, and the magnitude of increase was significantly greater than that found for the intracellular collagen biosynthetic enzymes protocollagen prolyl hydroxylase and lysyl hydroxylase. Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space. However, it was not possible to correlate the distribution pattern with a particular liver cell type. These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition.", "contents": "Biochemical and immunochemical study of lysyl oxidase in experimental hepatic fibrosis in the rat. Lysyl oxidase catalyzes the crosslinking of collagen and elastin. Lysyl oxidase activity was measured and localized in rat liver during the evolution of hepatic fibrosis induced by CCl4. Enzyme activity measured with DL-[6-3H]-lysine-labeled collagen substrates in liver and plasma increased sharply after approximately 3 wk of injection, reached a maximum at 6 wk, and then decreased. The increase in activity correlated histologically with early connective tissue septa formation, and the magnitude of increase was significantly greater than that found for the intracellular collagen biosynthetic enzymes protocollagen prolyl hydroxylase and lysyl hydroxylase. Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space. However, it was not possible to correlate the distribution pattern with a particular liver cell type. These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition."}
{"id": "PMID:26919", "title": "Ontogenetic appearance and disappearance of tyrosine hydroxylase and catecholamines in the rat embryo.", "content": "The ontogenetic pattern of noradrenergic differentiation in rat embryonic autonomic neuroblasts was defined in vivo. Noradrenergic specialization was examined by documenting the immunohistochemical appearance of tyrosine hydroxylase [Tyr-OH; tyrosine 3-monooxygenase; L-tyrosine,-tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the development of histofluorescence due to catecholamine (CA). Tyr-OH and CA were undetectable in the dorsal neural crest or the ventrally migrating crest cells and first appeared at 12.5 days of gestation (36--37 somite stage) in sympathoblasts that had formed sympathetic ganglion primordia. Fluorescence intensity and the number of fluorescent cells increased progressively thereafter. In addition, Tyr-OH and CA transiently appeared in scattered presumptive neuroblasts in the gut. The enzyme and transmitter were first detectable at 11.5 days of gestation and thereafter decreased progressively so that, by 14.5 days, only rare cells were encountered. There was remarkable synchrony in the appearance and disappearance of Tyr-OH and CA. These observations suggest that a number of noradrenergic transmitter mechanisms develop simultaneously in the differentiating neuroblast. The relevance of these results to the elucidation of developmental regulatory mechanisms is discussed.", "contents": "Ontogenetic appearance and disappearance of tyrosine hydroxylase and catecholamines in the rat embryo. The ontogenetic pattern of noradrenergic differentiation in rat embryonic autonomic neuroblasts was defined in vivo. Noradrenergic specialization was examined by documenting the immunohistochemical appearance of tyrosine hydroxylase [Tyr-OH; tyrosine 3-monooxygenase; L-tyrosine,-tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the development of histofluorescence due to catecholamine (CA). Tyr-OH and CA were undetectable in the dorsal neural crest or the ventrally migrating crest cells and first appeared at 12.5 days of gestation (36--37 somite stage) in sympathoblasts that had formed sympathetic ganglion primordia. Fluorescence intensity and the number of fluorescent cells increased progressively thereafter. In addition, Tyr-OH and CA transiently appeared in scattered presumptive neuroblasts in the gut. The enzyme and transmitter were first detectable at 11.5 days of gestation and thereafter decreased progressively so that, by 14.5 days, only rare cells were encountered. There was remarkable synchrony in the appearance and disappearance of Tyr-OH and CA. These observations suggest that a number of noradrenergic transmitter mechanisms develop simultaneously in the differentiating neuroblast. The relevance of these results to the elucidation of developmental regulatory mechanisms is discussed."}
{"id": "PMID:26925", "title": "Bacteriorhodopsin: lipid environment and conformational changes.", "content": "The polar lipids of the purple membrane were exchanged for different phosphatidylcholine species. The resulting complexes had the same protein to lipid-phosphorus ratio as the natural membrane, but only about 0.5-1.0 mole of original lipid was still present per mole of bacteriorhodopsin. In such complexes the bacteriorhodopsin photocycle is slowed down 10-20 times, but the strong protein-protein interaction is not abolished. Due to the slow rate of the photocycle we were able to measure in the light the ratio between net proton release and net accumulation of the last intermediate of the photocycle, the unprotonated M412. This ratio was not constant and equal to 1.0, as expected for a single deprotonation reaction, but varied with pH from 1.5 to 0.4. The variable ratio suggests that light-induced conformational changes occur in the nonchromophore part of the protein, which shift the pKa values of unidentified groups so as to cause binding or release of additional protons. A similar conclusion was drawn from experiments on the kinetics of proton transfer by bacteriorhodopsin in subbacterial particles of Halobacterium halobium and in reconstituted bacteriorhodopsin proteoliposomes. However, in this case light-induced association and dissociation of additional protons occurs simultaneously on different sides of the membrane.", "contents": "Bacteriorhodopsin: lipid environment and conformational changes. The polar lipids of the purple membrane were exchanged for different phosphatidylcholine species. The resulting complexes had the same protein to lipid-phosphorus ratio as the natural membrane, but only about 0.5-1.0 mole of original lipid was still present per mole of bacteriorhodopsin. In such complexes the bacteriorhodopsin photocycle is slowed down 10-20 times, but the strong protein-protein interaction is not abolished. Due to the slow rate of the photocycle we were able to measure in the light the ratio between net proton release and net accumulation of the last intermediate of the photocycle, the unprotonated M412. This ratio was not constant and equal to 1.0, as expected for a single deprotonation reaction, but varied with pH from 1.5 to 0.4. The variable ratio suggests that light-induced conformational changes occur in the nonchromophore part of the protein, which shift the pKa values of unidentified groups so as to cause binding or release of additional protons. A similar conclusion was drawn from experiments on the kinetics of proton transfer by bacteriorhodopsin in subbacterial particles of Halobacterium halobium and in reconstituted bacteriorhodopsin proteoliposomes. However, in this case light-induced association and dissociation of additional protons occurs simultaneously on different sides of the membrane."}
{"id": "PMID:26926", "title": "Proteins containing reductively aminated disaccharides: chemical and immunochemical characterization.", "content": "Synthetic glycoproteins can be prepared by reductive amination of proteins and reducing carbohydrates in the presence of sodium cyanoborohydride. The reaction proceeds readily in aqueous solution at pH 6--9 to give high degrees of substitution. The degree of substitution can be determined by amino acid analysis, as the 2 degrees amine linkage formed with the epsilon-amino groups of lysine is stable to acid-catalyzed protein hydrolysis conditions. Antisera have been obtained to bovine serum albumin conjugates containing reductively aminated cellobiose, lactose, and maltose. Preliminary experiments demonstrate that antiserum to the cellobiose-BSA conjugate is hapten-specific, and the structural features of the hapten recognized by the antibodies were established by hapten inhibition experiments. These studies demonstrate that antibodies recognize both the terminal beta-glucosyl and acyclic reduced glucosyl residues.", "contents": "Proteins containing reductively aminated disaccharides: chemical and immunochemical characterization. Synthetic glycoproteins can be prepared by reductive amination of proteins and reducing carbohydrates in the presence of sodium cyanoborohydride. The reaction proceeds readily in aqueous solution at pH 6--9 to give high degrees of substitution. The degree of substitution can be determined by amino acid analysis, as the 2 degrees amine linkage formed with the epsilon-amino groups of lysine is stable to acid-catalyzed protein hydrolysis conditions. Antisera have been obtained to bovine serum albumin conjugates containing reductively aminated cellobiose, lactose, and maltose. Preliminary experiments demonstrate that antiserum to the cellobiose-BSA conjugate is hapten-specific, and the structural features of the hapten recognized by the antibodies were established by hapten inhibition experiments. These studies demonstrate that antibodies recognize both the terminal beta-glucosyl and acyclic reduced glucosyl residues."}
{"id": "PMID:26933", "title": "Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa.", "content": "Adult male Swiss-Webster mice were housed either singly (isolated) or with a female (nonisolated). Aggressive behavior was evoked by introducing a group-housed male mouse (intruder) into the home cage of the isolated or nonisolated mouse (resident).d-Amphetamine, methamphetamine, methylphenidate, cocaine, and L-dopa decreased attack and threat behavior by resident mice, the isolates requiring 2--4 times higher drug doses for the antiaggressive effects than the nonisolates, d-Amphetamine, methamphetamine, and methylphenidate caused intruder mice to be more frequently attacked by their non-treated resident opponents, to escape more often, to assume the defensive upright posture less, and to move about more often. L-Dopa nonspecifically de creased all elements of agonistic and nonagonistic behavior, while the amphetamines and methylphenidate suppressed attacks, increased escapes, decreased upright postures, and increased nonagonistic locomotion. By contrast, cocaine's antiaggressive effects were remarkably specific, i.e., not accompanied by changes in other behavioral elements.", "contents": "Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa. Adult male Swiss-Webster mice were housed either singly (isolated) or with a female (nonisolated). Aggressive behavior was evoked by introducing a group-housed male mouse (intruder) into the home cage of the isolated or nonisolated mouse (resident).d-Amphetamine, methamphetamine, methylphenidate, cocaine, and L-dopa decreased attack and threat behavior by resident mice, the isolates requiring 2--4 times higher drug doses for the antiaggressive effects than the nonisolates, d-Amphetamine, methamphetamine, and methylphenidate caused intruder mice to be more frequently attacked by their non-treated resident opponents, to escape more often, to assume the defensive upright posture less, and to move about more often. L-Dopa nonspecifically de creased all elements of agonistic and nonagonistic behavior, while the amphetamines and methylphenidate suppressed attacks, increased escapes, decreased upright postures, and increased nonagonistic locomotion. By contrast, cocaine's antiaggressive effects were remarkably specific, i.e., not accompanied by changes in other behavioral elements."}
{"id": "PMID:26942", "title": "Effect of thoracentesis on arterial oxygen tension.", "content": "The acute effects of thoracentesis on arterial oxygenation were observed in 19 studies on 17 patients. Arterial blood samples were obtained prior to, immediately after, and 1 h after thoracentesis. Unpredictable changes in the arterial oxygen tension, ranging from -22 to +19 mm Hg were found immediately following thoracentesis. It was concluded that significant hypoxemia may result from thoracentesis due to aberration of ventilation-perfusion relationships. It is further suggested that oxygen therapy be routinely administered during and immediately after the procedure.", "contents": "Effect of thoracentesis on arterial oxygen tension. The acute effects of thoracentesis on arterial oxygenation were observed in 19 studies on 17 patients. Arterial blood samples were obtained prior to, immediately after, and 1 h after thoracentesis. Unpredictable changes in the arterial oxygen tension, ranging from -22 to +19 mm Hg were found immediately following thoracentesis. It was concluded that significant hypoxemia may result from thoracentesis due to aberration of ventilation-perfusion relationships. It is further suggested that oxygen therapy be routinely administered during and immediately after the procedure."}
{"id": "PMID:26943", "title": "Mean whole body intracellular pH in unanesthetized dogs: a revised method.", "content": "An improved method of calculating the mean whole body intracellular pH (pHi) by means of DMO in unanesthetized dogs is described. The elemination of DMO from the body fluid is assumed to follow a simple exponential decay with a time constant k1. The distribution of DMO into the extracellular and intracellular water is described by an exponential function (1-exp(-k2t)). From experiments in 9 unanesthetized dogs it was found that k1 = 0.008 h-1 and k2 = 1.325 h-1. Mean pHi was 7.08 +/- 0.05 at Pa(c02) = 4.1 kPa (31 mm Hg). The average difference between arterial blood and pHi was 0.35. No statistically different pHi values were found with data from arterial or mixed venous blood. Even after 24 h the method still yields reasonable values for pHi.", "contents": "Mean whole body intracellular pH in unanesthetized dogs: a revised method. An improved method of calculating the mean whole body intracellular pH (pHi) by means of DMO in unanesthetized dogs is described. The elemination of DMO from the body fluid is assumed to follow a simple exponential decay with a time constant k1. The distribution of DMO into the extracellular and intracellular water is described by an exponential function (1-exp(-k2t)). From experiments in 9 unanesthetized dogs it was found that k1 = 0.008 h-1 and k2 = 1.325 h-1. Mean pHi was 7.08 +/- 0.05 at Pa(c02) = 4.1 kPa (31 mm Hg). The average difference between arterial blood and pHi was 0.35. No statistically different pHi values were found with data from arterial or mixed venous blood. Even after 24 h the method still yields reasonable values for pHi."}
{"id": "PMID:26944", "title": "The influence of low, normal and high Pa(O2) on the respiratory effects of Pa(CO2) oscillations in anaesthetised cats.", "content": "The present study examines the influence of oxygen tension on the recurrent tidal volume changes caused by oscillations in arterial P(CO2). The oscillations have a period equal to two respiratory cycles, and are produced by giving alternately CO2 -enriched and CO2 -free gas mixtures. The results show alternation of the tidal volume with the same incidence (is greater than 50%) at low, normal and high oxygen tensions. However, the magnitudes of the breath-by-breath changes are significantly greater at low oxygen tension than at normal oxygen tension. Under high oxygen tension breath-by-breath tidal volume changes are indistinguishable from those at normal oxygen tension.", "contents": "The influence of low, normal and high Pa(O2) on the respiratory effects of Pa(CO2) oscillations in anaesthetised cats. The present study examines the influence of oxygen tension on the recurrent tidal volume changes caused by oscillations in arterial P(CO2). The oscillations have a period equal to two respiratory cycles, and are produced by giving alternately CO2 -enriched and CO2 -free gas mixtures. The results show alternation of the tidal volume with the same incidence (is greater than 50%) at low, normal and high oxygen tensions. However, the magnitudes of the breath-by-breath changes are significantly greater at low oxygen tension than at normal oxygen tension. Under high oxygen tension breath-by-breath tidal volume changes are indistinguishable from those at normal oxygen tension."}
{"id": "PMID:26945", "title": "Respiratory characteristics of opossum (Didelphis virginiana) blood during chronic anemia.", "content": "In five adult opossums (Didelphis virginiana), blood hemoglobin concentration was lowered from 12.3g% to 6.4g% by daily bleeding. Blood P50 rose significantly (P is less than 0.05) from 44.5 mm Hg to 47.4 mm Hg and the concentration of 2, 3-diphosphoglycerate (DPG) increased from 14.17 mumol/g Hb to 20.90 mumol/g Hb. The observed shift in blood oxygen affinity was of similar magnitude to that recorded in humans with a similar degree of anemia, but the concomitant rise in DPG concentration was greater in opossums than in humans. In the opossum the shift in P50 with anemia can be attributed entirely to the action of DPG as a non diffusible intraerythrocytic anion.", "contents": "Respiratory characteristics of opossum (Didelphis virginiana) blood during chronic anemia. In five adult opossums (Didelphis virginiana), blood hemoglobin concentration was lowered from 12.3g% to 6.4g% by daily bleeding. Blood P50 rose significantly (P is less than 0.05) from 44.5 mm Hg to 47.4 mm Hg and the concentration of 2, 3-diphosphoglycerate (DPG) increased from 14.17 mumol/g Hb to 20.90 mumol/g Hb. The observed shift in blood oxygen affinity was of similar magnitude to that recorded in humans with a similar degree of anemia, but the concomitant rise in DPG concentration was greater in opossums than in humans. In the opossum the shift in P50 with anemia can be attributed entirely to the action of DPG as a non diffusible intraerythrocytic anion."}
{"id": "PMID:26946", "title": "Oxygen transport in chicken embryos under hypothermal exposure.", "content": "Fertile hens' eggs incubated for 16 days at 38 degrees C were abruptly exposed to a temperature of 30 degrees C for 2 h and then determinations of blood gas parameters and the O2 dissociation curve were performed. In addition, O2 uptake was measured. Under hypothermal exposure the O2 dissociation curve showed a marked leftward shift in accordance with the increase in pH. The O2 saturation in arterialized blood of the allantoic vein reached almost 100%, and the blood S(O2) of the allantoic artery also increased up to about 50% in contrast with about 20% in normothermal controls. The blood flow rate through the chorioallantoic capillary plexus seemed to be almost identical with that of normothermal embryos. Because of the increased O2 affinity and the decreased O2 consumption, the systemic venous O2 reserve should be raised by hypothermal exposure. In connection with this conjecture, the redistribution of blood flow and O2 quantity by hypothermal exposure were calculated using the same circulation model as used in normothermal embryos. The result came closer to fetal lambs than to normothermal embryos.", "contents": "Oxygen transport in chicken embryos under hypothermal exposure. Fertile hens' eggs incubated for 16 days at 38 degrees C were abruptly exposed to a temperature of 30 degrees C for 2 h and then determinations of blood gas parameters and the O2 dissociation curve were performed. In addition, O2 uptake was measured. Under hypothermal exposure the O2 dissociation curve showed a marked leftward shift in accordance with the increase in pH. The O2 saturation in arterialized blood of the allantoic vein reached almost 100%, and the blood S(O2) of the allantoic artery also increased up to about 50% in contrast with about 20% in normothermal controls. The blood flow rate through the chorioallantoic capillary plexus seemed to be almost identical with that of normothermal embryos. Because of the increased O2 affinity and the decreased O2 consumption, the systemic venous O2 reserve should be raised by hypothermal exposure. In connection with this conjecture, the redistribution of blood flow and O2 quantity by hypothermal exposure were calculated using the same circulation model as used in normothermal embryos. The result came closer to fetal lambs than to normothermal embryos."}
{"id": "PMID:26947", "title": "Comparison of efflux rates of hydrogen and lactate ions from isolated muscles in vitro.", "content": "Relative rates of efflux of hydrogen and lactate ions from skeletal muscle in vitro were determined on isolated rat diaphragms and frog satorius muscles. After a period of lacate accumulation by stimulation in vitro, muscles were suspended in a small volume of Ringer solution for different time periods lasting up to 60 min. The pH change in the solution was monitored continuously. After the predetermined time period, samples of the muscle and the Ringer solution were analysed for lactate content. Results showed that in both types of muscles the rate of efflux of hydrogen ions exceeded that of lactate ions by factors of about 14 and 50 in the case of diaphragm and sartorius muscles respectively. Because of this difference observed in the efflux kinetics of hydrogen and lactate ions, it is evident that the lactate content of a body compartment does not represent the absolute hydrogen ion load of the same compartment, particularly during the early phase of the efflux process.", "contents": "Comparison of efflux rates of hydrogen and lactate ions from isolated muscles in vitro. Relative rates of efflux of hydrogen and lactate ions from skeletal muscle in vitro were determined on isolated rat diaphragms and frog satorius muscles. After a period of lacate accumulation by stimulation in vitro, muscles were suspended in a small volume of Ringer solution for different time periods lasting up to 60 min. The pH change in the solution was monitored continuously. After the predetermined time period, samples of the muscle and the Ringer solution were analysed for lactate content. Results showed that in both types of muscles the rate of efflux of hydrogen ions exceeded that of lactate ions by factors of about 14 and 50 in the case of diaphragm and sartorius muscles respectively. Because of this difference observed in the efflux kinetics of hydrogen and lactate ions, it is evident that the lactate content of a body compartment does not represent the absolute hydrogen ion load of the same compartment, particularly during the early phase of the efflux process."}
{"id": "PMID:26965", "title": "[D\u00e9termination of salivary pH by contact pH metry. Study of ph on the tongue and of the orifices of Wharton's and Stenon's ducts].", "content": "The authors describe an electrochemical technique for the measurement of salivary pH by contact. They present a critical study fo 167 cases. The values obtained are characteristic in terms of age and the site of determination (dorsal surface of the tongue, orifice of Wharton's or Stenon's ducts).", "contents": "[D\u00e9termination of salivary pH by contact pH metry. Study of ph on the tongue and of the orifices of Wharton's and Stenon's ducts]. The authors describe an electrochemical technique for the measurement of salivary pH by contact. They present a critical study fo 167 cases. The values obtained are characteristic in terms of age and the site of determination (dorsal surface of the tongue, orifice of Wharton's or Stenon's ducts)."}
{"id": "PMID:26966", "title": "The electrical potential difference and impedance between CSF and blood in unanesthetized man.", "content": "The electrical potential difference (PD) between cerebrospinal fluid (CSF) and blood has been studied extensively in animals. To obtain data from man the PD and impedance were recorded from the lumbar subarachnoid space of thirteen unanaesthetized patients with a presumably normal blood--brain barrier. The spontaneous PD ranged from 1 mV to 5 mV, CSF positive to blood. Hyperventilation and CO2-inhalation changed the PD with a mean slope of deltaPD/deltapHa of --4.16 mV/pH. The CSF-blood PD in unanaesthetized man is similar in direction to that found in dogs, goats and rats, but its sensitivity to change in arterial pH may be less.", "contents": "The electrical potential difference and impedance between CSF and blood in unanesthetized man. The electrical potential difference (PD) between cerebrospinal fluid (CSF) and blood has been studied extensively in animals. To obtain data from man the PD and impedance were recorded from the lumbar subarachnoid space of thirteen unanaesthetized patients with a presumably normal blood--brain barrier. The spontaneous PD ranged from 1 mV to 5 mV, CSF positive to blood. Hyperventilation and CO2-inhalation changed the PD with a mean slope of deltaPD/deltapHa of --4.16 mV/pH. The CSF-blood PD in unanaesthetized man is similar in direction to that found in dogs, goats and rats, but its sensitivity to change in arterial pH may be less."}
{"id": "PMID:26968", "title": "A short duration renal acidification test.", "content": "As earlier investigations of renal acidification capacity were poorly standardized it was considered important to develop a clinically useful method. The ability of the kidneys to acidify urine was studied in 19 normal persons by short ammonium chloride loading. Ammonium chloride was given in a dose of 150 mmol/m2 body surface in one of four different ways: whole tablets, crushed tablets, capsules and in solution. The degree of acidosis developed in each subject was measured in arterialized capillary blood samples. Urine was analysed for pH, titratable acid, ammonium ions (TA and NH4+) and phosphate. The excretion of TA, NH4+ and phosphate increased with the degree of acidosis in blood whilst urine pH decreased. The critical level appeared to lie around a base excess of -6 mmol/l below which all subjects could acidify their urine to a pH below 5.0. For clinical applications a frame of reference with tolerance limits is given for acidification capacity related to the degree of acidosis expressed as base excess.", "contents": "A short duration renal acidification test. As earlier investigations of renal acidification capacity were poorly standardized it was considered important to develop a clinically useful method. The ability of the kidneys to acidify urine was studied in 19 normal persons by short ammonium chloride loading. Ammonium chloride was given in a dose of 150 mmol/m2 body surface in one of four different ways: whole tablets, crushed tablets, capsules and in solution. The degree of acidosis developed in each subject was measured in arterialized capillary blood samples. Urine was analysed for pH, titratable acid, ammonium ions (TA and NH4+) and phosphate. The excretion of TA, NH4+ and phosphate increased with the degree of acidosis in blood whilst urine pH decreased. The critical level appeared to lie around a base excess of -6 mmol/l below which all subjects could acidify their urine to a pH below 5.0. For clinical applications a frame of reference with tolerance limits is given for acidification capacity related to the degree of acidosis expressed as base excess."}
{"id": "PMID:26969", "title": "Urine acidification capacity in renal stone formers.", "content": "A short ammonium chloride loading test was used in the investigation of renal acidification capacity of 51 patients with idiopathic recurrent renal stones containing calcium. Many of these patients had suffered from prolonged and severe stone disease. In 31% of the patients an impaired acidification with varying degrees of severity was found. Eight patients had defects suggesting distal renal tubular acidosis (RTA). One case with the complete and two cases with the incomplete form of RTA were found. A further five patients, who were all able to acidify their urine to an acid pH, had milder defects in the excretion of titratable acid and/or ammonium ions which may indicate an early stage of distal tubular acidosis. Six patients were suspected of having a proximal acidification defect, as they showed delayed responses to the ammonium chloride induced acidosis.", "contents": "Urine acidification capacity in renal stone formers. A short ammonium chloride loading test was used in the investigation of renal acidification capacity of 51 patients with idiopathic recurrent renal stones containing calcium. Many of these patients had suffered from prolonged and severe stone disease. In 31% of the patients an impaired acidification with varying degrees of severity was found. Eight patients had defects suggesting distal renal tubular acidosis (RTA). One case with the complete and two cases with the incomplete form of RTA were found. A further five patients, who were all able to acidify their urine to an acid pH, had milder defects in the excretion of titratable acid and/or ammonium ions which may indicate an early stage of distal tubular acidosis. Six patients were suspected of having a proximal acidification defect, as they showed delayed responses to the ammonium chloride induced acidosis."}
{"id": "PMID:26970", "title": "Bicarbonate re-absorption in renal stone patients with acidification defects.", "content": "A pathological renal response to ammonium chloride loading was found to be common in renal stone formers. In order to elicit further information about the impaired acidification capacity eight patients were investigated by bicarbonate loading. One patient with a mild acidification defect had normal tubular re-absorption of bicarbonate. Five of these eight patients with suspected proximal acidification defect and two patients with impaired distal acidification were found to have a low bicarbonate threshold and an increased, fractionated, bicarbonate excretion at a normal plasma bicarbonate level. Four of the patients with suspected, proximal, acidification defect reached a maximal re-absorption of bicarbonate (Tm) that was low, while three patients did not reach a Tm. These three factors indicate increased bicarbonate wastage from the kidneys. A constantly alkaline urine, such as exists in patients with proximal acidification defect may give rise to an increased risk of the precipitation of renal stones - primarily calcium-phosphate stones.", "contents": "Bicarbonate re-absorption in renal stone patients with acidification defects. A pathological renal response to ammonium chloride loading was found to be common in renal stone formers. In order to elicit further information about the impaired acidification capacity eight patients were investigated by bicarbonate loading. One patient with a mild acidification defect had normal tubular re-absorption of bicarbonate. Five of these eight patients with suspected proximal acidification defect and two patients with impaired distal acidification were found to have a low bicarbonate threshold and an increased, fractionated, bicarbonate excretion at a normal plasma bicarbonate level. Four of the patients with suspected, proximal, acidification defect reached a maximal re-absorption of bicarbonate (Tm) that was low, while three patients did not reach a Tm. These three factors indicate increased bicarbonate wastage from the kidneys. A constantly alkaline urine, such as exists in patients with proximal acidification defect may give rise to an increased risk of the precipitation of renal stones - primarily calcium-phosphate stones."}
{"id": "PMID:26972", "title": "Immunofluorescent detection of nuclear double-stranded RNA in situ in Vero and mosquito cells.", "content": "Double-stranded RNA (dsRNA) was detected in situ by indirect immunofluorescence with antibodies to dsRNA. It was seen in nuclei of Vero and Aedes albopictus cells, but not in BHK cells, KB cells, chick embryo fibroblasts, or HeLa cells. Reactive dsRNA was present in the nucleoplasm, but not in nucleoli or cytoplasm. Extracted RNA from the whole cell contained from 0.08 percent (BHK) to 0.46 percent (HeLa) dsRNA, as estimated by serological methods. This dsRNA, found in molecules having the size distribution of heterogeneous nuclear RNA, did not renature rapidly after denaturation. The quantity of dsRNA in total extracted RNA did not correlate with the presence or absence of nuclear staining in situ.", "contents": "Immunofluorescent detection of nuclear double-stranded RNA in situ in Vero and mosquito cells. Double-stranded RNA (dsRNA) was detected in situ by indirect immunofluorescence with antibodies to dsRNA. It was seen in nuclei of Vero and Aedes albopictus cells, but not in BHK cells, KB cells, chick embryo fibroblasts, or HeLa cells. Reactive dsRNA was present in the nucleoplasm, but not in nucleoli or cytoplasm. Extracted RNA from the whole cell contained from 0.08 percent (BHK) to 0.46 percent (HeLa) dsRNA, as estimated by serological methods. This dsRNA, found in molecules having the size distribution of heterogeneous nuclear RNA, did not renature rapidly after denaturation. The quantity of dsRNA in total extracted RNA did not correlate with the presence or absence of nuclear staining in situ."}
{"id": "PMID:26973", "title": "Sodium channel inactivation in squid axon is removed by high internal pH or tyrosine-specific reagents.", "content": "In squid axon, internal alkalinization from pH 7.1 to pH 10.2 results in a reversible decrease of the maximum inward current and the steady state sodium channel inactivation. Similar effects were observed after treatment of the axon with tetranitromethane or after iodination with lactoperoxidase. These results suggest that a tyrosine residue is an essential component of the inactivation process in this nerve.", "contents": "Sodium channel inactivation in squid axon is removed by high internal pH or tyrosine-specific reagents. In squid axon, internal alkalinization from pH 7.1 to pH 10.2 results in a reversible decrease of the maximum inward current and the steady state sodium channel inactivation. Similar effects were observed after treatment of the axon with tetranitromethane or after iodination with lactoperoxidase. These results suggest that a tyrosine residue is an essential component of the inactivation process in this nerve."}
{"id": "PMID:26974", "title": "Histamine H1 receptor-mediated guanosine 3',5'-monophosphate formation by cultured mouse neuroblastoma cells.", "content": "Incubation of cultured mouse neuroblastoma cells with histamine caused a rapid and marked increase in the formation of guanosine 3',5'-monophosphate (cyclic GMP) by these cells. Receptor agonists for H1, but not H2, caused this effect which was reduced by H1 but not by H2 or muscarinic acetylcholine receptor antagonists. These results indicate that activation of H1 receptors in these cultured nerve cells stimulated cyclic GMP formation.", "contents": "Histamine H1 receptor-mediated guanosine 3',5'-monophosphate formation by cultured mouse neuroblastoma cells. Incubation of cultured mouse neuroblastoma cells with histamine caused a rapid and marked increase in the formation of guanosine 3',5'-monophosphate (cyclic GMP) by these cells. Receptor agonists for H1, but not H2, caused this effect which was reduced by H1 but not by H2 or muscarinic acetylcholine receptor antagonists. These results indicate that activation of H1 receptors in these cultured nerve cells stimulated cyclic GMP formation."}
{"id": "PMID:26975", "title": "Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration.", "content": "Silicone pellets containing d-amphetamine base were implanted subcutaneously in rats. These pellets release amphetamine continuously for at least 10 days. Several days after implantation, swollen dopamine axons concomitant with large decreases in tyrosine hydroxylase activity were observed in the caudate nucleus. Decreased tyrosine hydroxylase activity was still present 110 days after pellet removal in the caudate but not in several other brain regions, nor in the caudate of rats injected with an equivalent amount of amphetamine in daily injections. This implies that continuous amphetamine administration has a selective neurotoxic effect on dopamine terminals in the caudate.", "contents": "Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Silicone pellets containing d-amphetamine base were implanted subcutaneously in rats. These pellets release amphetamine continuously for at least 10 days. Several days after implantation, swollen dopamine axons concomitant with large decreases in tyrosine hydroxylase activity were observed in the caudate nucleus. Decreased tyrosine hydroxylase activity was still present 110 days after pellet removal in the caudate but not in several other brain regions, nor in the caudate of rats injected with an equivalent amount of amphetamine in daily injections. This implies that continuous amphetamine administration has a selective neurotoxic effect on dopamine terminals in the caudate."}
{"id": "PMID:26976", "title": "Kainic acid lesions of the striatum dissociate amphetamine and apomorphine stereotypy: similarities to Huntingdon's chorea.", "content": "Kainic acid lesion of cell bodies in the dorsal striatum enhanced the stereotypy-producing effects of d-amphetamine without affecting the sterotypy produced by the direct receptor agonist apomorphine. This pattern of results parallels that found in patients suffering from Hungtington's chorea, thus strengthening the parallels between the kainic acid animal model and the human disease state initially suggested on biochemical gounds. The present results further suggest a dissociation of the mechanisms involved in the production of stereotypy by these two drugs, perhaps in terms of differential involvement of the striato-nigral negative feedback loop.", "contents": "Kainic acid lesions of the striatum dissociate amphetamine and apomorphine stereotypy: similarities to Huntingdon's chorea. Kainic acid lesion of cell bodies in the dorsal striatum enhanced the stereotypy-producing effects of d-amphetamine without affecting the sterotypy produced by the direct receptor agonist apomorphine. This pattern of results parallels that found in patients suffering from Hungtington's chorea, thus strengthening the parallels between the kainic acid animal model and the human disease state initially suggested on biochemical gounds. The present results further suggest a dissociation of the mechanisms involved in the production of stereotypy by these two drugs, perhaps in terms of differential involvement of the striato-nigral negative feedback loop."}
{"id": "PMID:26978", "title": "Posterior spinal fusion with Harrington instrumentation using \"balanced\" anesthesia.", "content": "In our experience nitrous oxide-oxygen-morphine-curare anesthesia has proved preferable because of the need for swifly awakening patients after instrumentation to ascertain neurologic status. Adjunctively, doxapram has been used to awaken patients in a predictably short time span. To prevent massive blood loss, hypotension has been attained by pentolinium, trimethaphan camsylate, and sodium nitroprusside.", "contents": "Posterior spinal fusion with Harrington instrumentation using \"balanced\" anesthesia. In our experience nitrous oxide-oxygen-morphine-curare anesthesia has proved preferable because of the need for swifly awakening patients after instrumentation to ascertain neurologic status. Adjunctively, doxapram has been used to awaken patients in a predictably short time span. To prevent massive blood loss, hypotension has been attained by pentolinium, trimethaphan camsylate, and sodium nitroprusside."}
{"id": "PMID:26980", "title": "Filariasis in West Kalimantan (Borneo), Indonesia.", "content": "A survey was carried out among persons residing in 8 villages in the Province of West Kalimantan, Indonesia to determine the prevalence of filariasis. Finger tip blood smears were obtained at night from over 3,000 people and microfilariae of Brugia malayi were found in 108 (3.5%) and Wuchereria bancrofti in 10 (0.3%). Most B. malayi (96 carriers) was found in Kakap, a village near the coast, 20 km from the provincial capital of Pontianak. Nine of 10 cases of W. bancrofti were located in Pahauman, a village 130 km northeast of the provincial capital. Periodicity studies indicate the strain of B. malayi to be subperiodic. In Kakap 18% of 226 persons examined had a clinical history of filariasis and elephantiasis was seen in 13%. This is the first report of rural bancroftian filariasis in the area. A few Mansonia species of mosquitoes were examined but none were infected with filarial larvae.", "contents": "Filariasis in West Kalimantan (Borneo), Indonesia. A survey was carried out among persons residing in 8 villages in the Province of West Kalimantan, Indonesia to determine the prevalence of filariasis. Finger tip blood smears were obtained at night from over 3,000 people and microfilariae of Brugia malayi were found in 108 (3.5%) and Wuchereria bancrofti in 10 (0.3%). Most B. malayi (96 carriers) was found in Kakap, a village near the coast, 20 km from the provincial capital of Pontianak. Nine of 10 cases of W. bancrofti were located in Pahauman, a village 130 km northeast of the provincial capital. Periodicity studies indicate the strain of B. malayi to be subperiodic. In Kakap 18% of 226 persons examined had a clinical history of filariasis and elephantiasis was seen in 13%. This is the first report of rural bancroftian filariasis in the area. A few Mansonia species of mosquitoes were examined but none were infected with filarial larvae."}
{"id": "PMID:26982", "title": "Cation and hydrogen ion effect on canine acid and gastrin output.", "content": "Differential stimulating effects on the parietal cell of dogs by calcium, magnesium and sodium were noted only at an alkaline pH. Acid inhibited the parietal cell, and antral perfusion did not cause gastrin stimulation at any pH level. The pH of the milieu of the parietal cell appears to be a more critical regulator of acid secretion than physiologic antral gastrin variation.", "contents": "Cation and hydrogen ion effect on canine acid and gastrin output. Differential stimulating effects on the parietal cell of dogs by calcium, magnesium and sodium were noted only at an alkaline pH. Acid inhibited the parietal cell, and antral perfusion did not cause gastrin stimulation at any pH level. The pH of the milieu of the parietal cell appears to be a more critical regulator of acid secretion than physiologic antral gastrin variation."}
{"id": "PMID:26983", "title": "A new model for the study of septic shock.", "content": "Septic shock was produced in 28 healthy mongrel dogs by injecting 10(8) Escherichia coli organisms per kilogram into the gallbladder following division of the cystic artery and duct. Based upon the circulatory responses and the mortality, two distinct groups emerged. In one, the cardiac index decreased significantly, and the total peripheral resistance was elevated. In the other, the cardiac index increased significantly, and the total peripheral resistance was significantly lower. The average survival time in the former group was three days and, in the latter, five days. The physiopathology of this model is remarkably similar to that of human septic shock. Studies are planned to further describe this model to increase its utility in the study of septic shock.", "contents": "A new model for the study of septic shock. Septic shock was produced in 28 healthy mongrel dogs by injecting 10(8) Escherichia coli organisms per kilogram into the gallbladder following division of the cystic artery and duct. Based upon the circulatory responses and the mortality, two distinct groups emerged. In one, the cardiac index decreased significantly, and the total peripheral resistance was elevated. In the other, the cardiac index increased significantly, and the total peripheral resistance was significantly lower. The average survival time in the former group was three days and, in the latter, five days. The physiopathology of this model is remarkably similar to that of human septic shock. Studies are planned to further describe this model to increase its utility in the study of septic shock."}
{"id": "PMID:26989", "title": "Pus, deoxyribonucleic acid, and sputum viscosity.", "content": "On 100 sputum specimens selected from patients suffering  from chronic bronchitis, bronchiectasis, asthma, and cystic fibrosis total deoxyribonucleic acid (DNA) content has been related to macroscopic type, to total dry weight yield, and to the apparent viscosity of the secretion at 1350 s-1: since DNA may be present, either as fibres or within cells, in one-third of the specimens the contribution of each form to the apparent viscosity was assessed. The effect on sputum viscosity of the addition of DNA in vitro has also been studied. Whereas between mucoid, mucopurulent, and purulent macroscopic types a significant difference in total DNA and dry weight yield has been found, viscosity was not significantly correlated with purulence. Similarly, the concentration of either cells or fibres correlated significantly with total DNA but not with viscosity. The in vitro addition of DNA to sputum caused a significant increase in its viscosity, and reasons for the differences between the iv vivo and in vitro effect are discussed. Certain constituents of purulent sputum tend to increase viscosity and others to reduce it, and the influence of these varies in the several diseases studied.", "contents": "Pus, deoxyribonucleic acid, and sputum viscosity. On 100 sputum specimens selected from patients suffering  from chronic bronchitis, bronchiectasis, asthma, and cystic fibrosis total deoxyribonucleic acid (DNA) content has been related to macroscopic type, to total dry weight yield, and to the apparent viscosity of the secretion at 1350 s-1: since DNA may be present, either as fibres or within cells, in one-third of the specimens the contribution of each form to the apparent viscosity was assessed. The effect on sputum viscosity of the addition of DNA in vitro has also been studied. Whereas between mucoid, mucopurulent, and purulent macroscopic types a significant difference in total DNA and dry weight yield has been found, viscosity was not significantly correlated with purulence. Similarly, the concentration of either cells or fibres correlated significantly with total DNA but not with viscosity. The in vitro addition of DNA to sputum caused a significant increase in its viscosity, and reasons for the differences between the iv vivo and in vitro effect are discussed. Certain constituents of purulent sputum tend to increase viscosity and others to reduce it, and the influence of these varies in the several diseases studied."}
{"id": "PMID:26992", "title": "Androgen concentration and partial characterization of 5alpha reductase in the epididymis of the rhesus monkey.", "content": "The 5alpha reductase activity ofthe monkey epididymis was studied. The enzyme was found in particulate subcellular fractions, its distribution closely resembling that of the microsomal marker enzyme NADPH: cytochrome c reductase, suggesting an association of 5alpha reductase with membranes of the endoplasmic reticulum. Maximal enzyme activity was found at pH 5.4 and at 32--37 C. The crude nuclear preparation had a Km: 0.315 x 10(-6)M and Vmax: 168 pmoles/mg protein/h. The microsomal enzyme had a Km: 0.243 x 10(-6)M and Vmax: 828 pmoles/mg protein/h. Neither enzyme preparation was affected by addition to the incubation media of dihydrotestosterone (DHT) or 5alpha-androstane-3alpha,17beta-diol. The endogenous androgen concentration in the epididymides of 2 different monkeys, in ng/g wet weight was: DHT 20.81 +/- 1.98; T: 9.0L +/- 2.83; diol: 3.03 +/- 0.41.", "contents": "Androgen concentration and partial characterization of 5alpha reductase in the epididymis of the rhesus monkey. The 5alpha reductase activity ofthe monkey epididymis was studied. The enzyme was found in particulate subcellular fractions, its distribution closely resembling that of the microsomal marker enzyme NADPH: cytochrome c reductase, suggesting an association of 5alpha reductase with membranes of the endoplasmic reticulum. Maximal enzyme activity was found at pH 5.4 and at 32--37 C. The crude nuclear preparation had a Km: 0.315 x 10(-6)M and Vmax: 168 pmoles/mg protein/h. The microsomal enzyme had a Km: 0.243 x 10(-6)M and Vmax: 828 pmoles/mg protein/h. Neither enzyme preparation was affected by addition to the incubation media of dihydrotestosterone (DHT) or 5alpha-androstane-3alpha,17beta-diol. The endogenous androgen concentration in the epididymides of 2 different monkeys, in ng/g wet weight was: DHT 20.81 +/- 1.98; T: 9.0L +/- 2.83; diol: 3.03 +/- 0.41."}
{"id": "PMID:26993", "title": "Study of complex marine sterol mixtures by mass-analyzed ion kinetic energy spectrometry.", "content": "Mass-analyzed ion kinetic energy spectrometry (MIKE) is shown to be an efficient and rapid method for the analysis of complex sterol mixtures. The method has been applied to the study of the free sterol fractions of five marine and one freshwater invertebrates.", "contents": "Study of complex marine sterol mixtures by mass-analyzed ion kinetic energy spectrometry. Mass-analyzed ion kinetic energy spectrometry (MIKE) is shown to be an efficient and rapid method for the analysis of complex sterol mixtures. The method has been applied to the study of the free sterol fractions of five marine and one freshwater invertebrates."}
{"id": "PMID:26994", "title": "Influence of experimental cryptorchidism on cholesterol side-chain cleavage enzyme and delta5-3beta-hydroxysteroid dehydrogenase activities in rat testes.", "content": "Testicular cholesterol side-chain cleavage enzyme (CSCCE) and delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activities were assessed 12 hours and 2, 4, 8, 16, and 32 days after surgical induction of bilateral cryptorchidism in adult rats. Within 12 hours after surgery CSCCE activity (expressed as dpm of isocaproic acid-14C formed from cholesterol-26-14C/3 hours/testis) was significantly reduced (P less than 0.01) in cryptorchid testes to approximately 55% of sham-operated control values and remained depressed at less than 50% of control activities 2, 4, 16, and 32 days after surgery. Cryptorchid testis delta5-3beta-HSD activity (measured by a pregnenolone substrate-depletion assay and expressed as mumoles of products/30 minutes/testis) did not differ from controls (P greater than 0.05) 1/2, 2, or 4 days after translocation of testes to the abdominal cavity. By day 8 of cryptorchidism, however, delta5-3beta-HSD activity was reduced to 60% of control values (P less than 0.05) and continued to decline to approximately 30% of controls during the remainder of the experimental period. These observed alterations in enzyme activities suggest an impairment in the ability of cryptorchid rat testes to synthesize androgens and further indicate that testicular CSCCE is more acutely sensitive to the cryptorchid milieu than delta5-3beta-HSD.", "contents": "Influence of experimental cryptorchidism on cholesterol side-chain cleavage enzyme and delta5-3beta-hydroxysteroid dehydrogenase activities in rat testes. Testicular cholesterol side-chain cleavage enzyme (CSCCE) and delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activities were assessed 12 hours and 2, 4, 8, 16, and 32 days after surgical induction of bilateral cryptorchidism in adult rats. Within 12 hours after surgery CSCCE activity (expressed as dpm of isocaproic acid-14C formed from cholesterol-26-14C/3 hours/testis) was significantly reduced (P less than 0.01) in cryptorchid testes to approximately 55% of sham-operated control values and remained depressed at less than 50% of control activities 2, 4, 16, and 32 days after surgery. Cryptorchid testis delta5-3beta-HSD activity (measured by a pregnenolone substrate-depletion assay and expressed as mumoles of products/30 minutes/testis) did not differ from controls (P greater than 0.05) 1/2, 2, or 4 days after translocation of testes to the abdominal cavity. By day 8 of cryptorchidism, however, delta5-3beta-HSD activity was reduced to 60% of control values (P less than 0.05) and continued to decline to approximately 30% of controls during the remainder of the experimental period. These observed alterations in enzyme activities suggest an impairment in the ability of cryptorchid rat testes to synthesize androgens and further indicate that testicular CSCCE is more acutely sensitive to the cryptorchid milieu than delta5-3beta-HSD."}
{"id": "PMID:26995", "title": "Lack of correlation between splenic and marrow hematopoiesis following irradiation or irradiation and transplantation in mice.", "content": "Differences were seen in the relative importance of spleen and marrow in early erythroid regeneration of lethally irradiated mice given spleen or marrow cell transplants compared with that in sublethally irradiated mice with surviving endogenous hematopoietic cells. Radioactive iron uptake was predominantly in the spleen of mice with transplants and in the marrow of endogenously recovering mice. Visable spleen colony counts increased from day 4 to day 7 and plateaued through day 10 in the transplant system, but shoed a small abortive rise with a 5-day peak, followed by a steady increase from days 6 to 10 in the endogenous system. Comparisons of peroxidase-positive cells (granulocytes) in the marrow of femurs and humeri and iron uptake in marrow and spleen suggested that repopulation of the marrow and spleen were independent, while that of different areas of the marrow was interrelated. The interrelationship of the rate of marrow regeneration was closer in the endogenous than in the transplant system.", "contents": "Lack of correlation between splenic and marrow hematopoiesis following irradiation or irradiation and transplantation in mice. Differences were seen in the relative importance of spleen and marrow in early erythroid regeneration of lethally irradiated mice given spleen or marrow cell transplants compared with that in sublethally irradiated mice with surviving endogenous hematopoietic cells. Radioactive iron uptake was predominantly in the spleen of mice with transplants and in the marrow of endogenously recovering mice. Visable spleen colony counts increased from day 4 to day 7 and plateaued through day 10 in the transplant system, but shoed a small abortive rise with a 5-day peak, followed by a steady increase from days 6 to 10 in the endogenous system. Comparisons of peroxidase-positive cells (granulocytes) in the marrow of femurs and humeri and iron uptake in marrow and spleen suggested that repopulation of the marrow and spleen were independent, while that of different areas of the marrow was interrelated. The interrelationship of the rate of marrow regeneration was closer in the endogenous than in the transplant system."}
{"id": "PMID:26998", "title": "Human red cell content of cyclic nucleotides and cations upon beta-adrenergic blockade.", "content": "The content of cyclic nucleotides (cAMP, cGMP) and Mg2+, Zn2+,Na+ and  K+ was determined in human erythrocytes and after beta-adrenergic blockade in healthy individuals. The figures for cAMP and cGMP were 4.20 and 3.36 nmoles/ l intracellular volume, respectively. Only slight effects on the cyclic nucleotide content as well as on cation content were seen upon beta-blockade in the erythrocytes. It is concluded that the single determination of red cell cAMP is not a sufficient indicator of beta-adrenergic blockade. The determination of cAMP in combination with cGMP, Zn2+ and Na+ might reflect a beta-adrenergic blockade.", "contents": "Human red cell content of cyclic nucleotides and cations upon beta-adrenergic blockade. The content of cyclic nucleotides (cAMP, cGMP) and Mg2+, Zn2+,Na+ and  K+ was determined in human erythrocytes and after beta-adrenergic blockade in healthy individuals. The figures for cAMP and cGMP were 4.20 and 3.36 nmoles/ l intracellular volume, respectively. Only slight effects on the cyclic nucleotide content as well as on cation content were seen upon beta-blockade in the erythrocytes. It is concluded that the single determination of red cell cAMP is not a sufficient indicator of beta-adrenergic blockade. The determination of cAMP in combination with cGMP, Zn2+ and Na+ might reflect a beta-adrenergic blockade."}
{"id": "PMID:26999", "title": "Denervation supersensitivity of the urethra to alpha-adrenergics in the chronic neurogenic bladder.", "content": "The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholineR and a group of 10 control subjects. A supersensitive response to the administration of an alpha-stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of alpha-adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of alpha-adrenergic predominance in the urethra which is now believed to be dually innervated.", "contents": "Denervation supersensitivity of the urethra to alpha-adrenergics in the chronic neurogenic bladder. The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholineR and a group of 10 control subjects. A supersensitive response to the administration of an alpha-stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of alpha-adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of alpha-adrenergic predominance in the urethra which is now believed to be dually innervated."}
{"id": "PMID:26996", "title": "[Content of adenine nucleotides and creatinephosphate in brain, myocardium, liver and skeletal muscle under combined action of hypercapnia, hypoxia and cooling].", "content": "Cooling of rats under conditions of hypercapina and hypoxia induced no changes in the content of adenine nucleotides in the brain and skeletal muscles and decreased their concentration in the liver and myocardium. The content of creatine phosphate increased in the brain, but had no changes in the other tissues. 48 hours after cooling the amount of adenine nucleotides in the brain was higher as compared with the initial values, that was due to an increase in the ATP concentration; in the other tissues the contents of adenine nucleotides did not differ from that of the intact rats. The repeated action (48 hours after the first influences) caused no changes in the contents of adenine nucleotides in skeletal muscles and decreased them in the myocardium and liver. In the brain their amount and the content of creatinephosphate were increased as related to the intact rats. In the brain and myocardium the level of NADPH decreased after the first action and 48 hours after impact it restored up to the inital values. After repeated impact the level of NADPH in the brain restored up to initial values, in the myocardium it was increased.", "contents": "[Content of adenine nucleotides and creatinephosphate in brain, myocardium, liver and skeletal muscle under combined action of hypercapnia, hypoxia and cooling]. Cooling of rats under conditions of hypercapina and hypoxia induced no changes in the content of adenine nucleotides in the brain and skeletal muscles and decreased their concentration in the liver and myocardium. The content of creatine phosphate increased in the brain, but had no changes in the other tissues. 48 hours after cooling the amount of adenine nucleotides in the brain was higher as compared with the initial values, that was due to an increase in the ATP concentration; in the other tissues the contents of adenine nucleotides did not differ from that of the intact rats. The repeated action (48 hours after the first influences) caused no changes in the contents of adenine nucleotides in skeletal muscles and decreased them in the myocardium and liver. In the brain their amount and the content of creatinephosphate were increased as related to the intact rats. In the brain and myocardium the level of NADPH decreased after the first action and 48 hours after impact it restored up to the inital values. After repeated impact the level of NADPH in the brain restored up to initial values, in the myocardium it was increased."}
{"id": "PMID:27000", "title": "Uropharmacology: VII. Ganglionic stimulating and blocking agents.", "content": "A classification of the various ganglionic stimulants and blockers is presented, and their pharmacologic effects on the urinary bladder and urethra are discussed. Ganglionic stimulating drugs are of considerable interest in investigational work but are not presently used therapeutically. Ganglionic blockers include hexamethonium, tetraethylammonium, mecamylamine emepronium, pentolinium, chlorisondamine, and pemipidine. Of the numerous ganglionic blocking drugs that have appeared on the therapeutic scene, only mecamylamine, pentolinium, and trimethaphan are currently official.", "contents": "Uropharmacology: VII. Ganglionic stimulating and blocking agents. A classification of the various ganglionic stimulants and blockers is presented, and their pharmacologic effects on the urinary bladder and urethra are discussed. Ganglionic stimulating drugs are of considerable interest in investigational work but are not presently used therapeutically. Ganglionic blockers include hexamethonium, tetraethylammonium, mecamylamine emepronium, pentolinium, chlorisondamine, and pemipidine. Of the numerous ganglionic blocking drugs that have appeared on the therapeutic scene, only mecamylamine, pentolinium, and trimethaphan are currently official."}
{"id": "PMID:26997", "title": "[Immobilized form of Streptomyces griseus proteases complex].", "content": "The immobilized form of proteases complex of Str. griseus actinomycete is obtained by means of glutaric aldehyde with aminoethyl cellulose. Hydrolysis of synthetic substrates showed that the system of peptide hydrolases is bound, but the ratio of activities as compared to the initial proteolytic complex changes, pH-optimum of the total proteolytic activity, pH- and temperature optima of stability are not changed with immobilization. On the whole no essential stabilization of the complex was observed. After five repeated cycles of the immobilized form utilization of the activity loss accounts for 40-60%.", "contents": "[Immobilized form of Streptomyces griseus proteases complex]. The immobilized form of proteases complex of Str. griseus actinomycete is obtained by means of glutaric aldehyde with aminoethyl cellulose. Hydrolysis of synthetic substrates showed that the system of peptide hydrolases is bound, but the ratio of activities as compared to the initial proteolytic complex changes, pH-optimum of the total proteolytic activity, pH- and temperature optima of stability are not changed with immobilization. On the whole no essential stabilization of the complex was observed. After five repeated cycles of the immobilized form utilization of the activity loss accounts for 40-60%."}
{"id": "PMID:27001", "title": "[Biochemical and hematological changes in the blood of horses after the \"Velk\u00e1 Pardubick\u00e1\" steeple chase].", "content": "Blood parameters were studied in two groups of horses in the \"Velk\u00e1 Pardubick\u00e1\" steeple-chase in 1974, 1975 and 1976. After the race, the levels of lactate showed a manifold increase; an increase was also ascertained in the levels of glucose, sodium, potassium, haemoglobin, in the haematocrit value and in the number of erythrocytes. The following parameters significantly dropped: the levels of acid-base balance - pH, base excess, bicarbonate levels. It was proved that the values of the same parameters in horses during training were incomparably lower. It is advisable to examine horses thoroughly during training and to use the results of training for the evaluation of their condition before difficult races.", "contents": "[Biochemical and hematological changes in the blood of horses after the \"Velk\u00e1 Pardubick\u00e1\" steeple chase]. Blood parameters were studied in two groups of horses in the \"Velk\u00e1 Pardubick\u00e1\" steeple-chase in 1974, 1975 and 1976. After the race, the levels of lactate showed a manifold increase; an increase was also ascertained in the levels of glucose, sodium, potassium, haemoglobin, in the haematocrit value and in the number of erythrocytes. The following parameters significantly dropped: the levels of acid-base balance - pH, base excess, bicarbonate levels. It was proved that the values of the same parameters in horses during training were incomparably lower. It is advisable to examine horses thoroughly during training and to use the results of training for the evaluation of their condition before difficult races."}
{"id": "PMID:27011", "title": "Automated antibody detection in a low ionic strength (glycine) medium.", "content": "Modifications were introduced into the low ionic strength system of Lalezari. Glycine was added in place of acidified glucose and the sensitisation and aggregation phases were segregated. In the automated glycine system a stable baseline is readily obtained as strong cell aggregation, with risk of cell adhesion to coil walls, is restricted to the last few turns of the aggregation phase. The automated glycine system is sensitive to a concentration of 0.0015 microgram/ml of anti-D diluted in saline and to 0.006 microgram/ml of anti-D in serum. Antibodies of a broad range of specificity are detectable.", "contents": "Automated antibody detection in a low ionic strength (glycine) medium. Modifications were introduced into the low ionic strength system of Lalezari. Glycine was added in place of acidified glucose and the sensitisation and aggregation phases were segregated. In the automated glycine system a stable baseline is readily obtained as strong cell aggregation, with risk of cell adhesion to coil walls, is restricted to the last few turns of the aggregation phase. The automated glycine system is sensitive to a concentration of 0.0015 microgram/ml of anti-D diluted in saline and to 0.006 microgram/ml of anti-D in serum. Antibodies of a broad range of specificity are detectable."}
{"id": "PMID:27006", "title": "[Protein inhibitor of cyclic nucleotide phosphodiesterase in the retina in hereditary degeneration].", "content": "Thermostable protein fraction from retina of rats with hereditary retinal dystrophy (Hunter and Campbell strains) did not inhibit cyclic nucleotide phosphodiesterase. At the same time an inhibitory component, found in retina of Wistar rat, rabbit, frog and lamprey, was similar to the component from bovine retina. Quantity of the inhibitory component in normal rat retina decreased considerably within postnatal period (12 days--3 months). Thermostable proteins, isolated from Campbell rat retina, differed from that of Hunters' one by electrophoretic properties while both preparations were dissimilar to the protein of normal rat. Protein bands, containing inhibitory component from dystrophic rat retina, appear to be less distinct as compared to those of normal rat. These proteins, eluated from the bands of Campbell rats, activated phosphodiesterase but the preparations from Hunter rats did not influence on it.", "contents": "[Protein inhibitor of cyclic nucleotide phosphodiesterase in the retina in hereditary degeneration]. Thermostable protein fraction from retina of rats with hereditary retinal dystrophy (Hunter and Campbell strains) did not inhibit cyclic nucleotide phosphodiesterase. At the same time an inhibitory component, found in retina of Wistar rat, rabbit, frog and lamprey, was similar to the component from bovine retina. Quantity of the inhibitory component in normal rat retina decreased considerably within postnatal period (12 days--3 months). Thermostable proteins, isolated from Campbell rat retina, differed from that of Hunters' one by electrophoretic properties while both preparations were dissimilar to the protein of normal rat. Protein bands, containing inhibitory component from dystrophic rat retina, appear to be less distinct as compared to those of normal rat. These proteins, eluated from the bands of Campbell rats, activated phosphodiesterase but the preparations from Hunter rats did not influence on it."}
{"id": "PMID:27010", "title": "[Increase in tryptic digestibility of dietary proteins in the stomach].", "content": "The trypsin assailability of food proteins (bread, dried milk and egg powder pastes) subjected for different periods of time to the action of the gastric juice directly in the stomach was studied by taking account of the specific topography of its content. It is shown that foodstuffs proteins can be increasingly assailable with trypsin as a result of the action exerted upon them in the stomach by the secretion of its glands. For different food proteins and at different time after feeding the animals as well as in different layers of the gastric contents this effect manifests itself dissimilarly. The trypsin assailability of food proteins increases in the layer near the mucosa and in the antral layers of the gastric contents. A higher trypsin assailability of food proteins is directly related to the level of the proteins hydrolysis in the stomach, to the acidity of the gastric contents and, especially, to its proteolytic activity.", "contents": "[Increase in tryptic digestibility of dietary proteins in the stomach]. The trypsin assailability of food proteins (bread, dried milk and egg powder pastes) subjected for different periods of time to the action of the gastric juice directly in the stomach was studied by taking account of the specific topography of its content. It is shown that foodstuffs proteins can be increasingly assailable with trypsin as a result of the action exerted upon them in the stomach by the secretion of its glands. For different food proteins and at different time after feeding the animals as well as in different layers of the gastric contents this effect manifests itself dissimilarly. The trypsin assailability of food proteins increases in the layer near the mucosa and in the antral layers of the gastric contents. A higher trypsin assailability of food proteins is directly related to the level of the proteins hydrolysis in the stomach, to the acidity of the gastric contents and, especially, to its proteolytic activity."}
{"id": "PMID:27009", "title": "[Dynamics and mechanism of mineral metabolic disorders in excessive phosphorus content in the diet].", "content": "Keeping rats on a ration with a 1:3 proportion of calcium and phosphorus for 2 weeks results in hyperprosphatemia, hypocalcemia and renal calcinosis with uremia. When putting these animals on a food ration with the calcium and phosphorus ratio of 1:1 the concentration of these elements in the blood quickly returns back to normal, while renal calcinosis continues for the whole period of observation (7 months). The growing animals are more sensitive to a phosphorus excess than are the adult ones. An excessive consumption of phosphorus leads to its increased excretion with the urine with concurrent diminution of the calcium excretion. The blood and urine pH then experiences no change, whereas the ability of the turned inside out segments of the small intestine to absorb calcium as against the concentration gradient (active transport) in vitro not only does not diminish, but initially even goes up. It is suggested that the excess phosphorus content in the food ration tends to directly derange absorption of calcium in the intestines, this resulting in the development of hypocalciemia, hyperparathyroidism and calcinosis of the viscera and tissues.", "contents": "[Dynamics and mechanism of mineral metabolic disorders in excessive phosphorus content in the diet]. Keeping rats on a ration with a 1:3 proportion of calcium and phosphorus for 2 weeks results in hyperprosphatemia, hypocalcemia and renal calcinosis with uremia. When putting these animals on a food ration with the calcium and phosphorus ratio of 1:1 the concentration of these elements in the blood quickly returns back to normal, while renal calcinosis continues for the whole period of observation (7 months). The growing animals are more sensitive to a phosphorus excess than are the adult ones. An excessive consumption of phosphorus leads to its increased excretion with the urine with concurrent diminution of the calcium excretion. The blood and urine pH then experiences no change, whereas the ability of the turned inside out segments of the small intestine to absorb calcium as against the concentration gradient (active transport) in vitro not only does not diminish, but initially even goes up. It is suggested that the excess phosphorus content in the food ration tends to directly derange absorption of calcium in the intestines, this resulting in the development of hypocalciemia, hyperparathyroidism and calcinosis of the viscera and tissues."}
{"id": "PMID:27019", "title": "Metabolism of atenolol in man.", "content": "1. The disposition and metabolism of 1-(4-carbamoyl[14C]methylphenoxy)-3-isopropylaminopan-2-ol (atenolol, Tenormin) has been studied in man following oral and intravenous doses. 2. Approx. 50% of an oral dose was eliminated in urine; the major radiolabelled component was atenolol (approx. 90%). Faecal extracts also contained largely unchanged atenolol, with small amounts of more polar metabolites. Biliary excretion of atenolol and its metabolites is not a major route of elimination in man. Metabolism of the compound is not extensive and route-dependent modes of metabolism do not appear to complicate the position. 3. Atenolol appeared to be the only major radiolabelled component in blood. 4. Oral doses of atenolol are incompletely absorbed (range 46-62%), even when formulated as a solution. 5. 1-[4-(C-Carbamoylhydroxymethyl)phenoxy]-3-isopropylaminopropan-2-ol was a minor urinary metabolite, which has only one tenth the activity of the parent compound as a beta-adrenergic blocking agent in the rat. 6. Pharmacological activity in man appears to be due to atenolol alone.", "contents": "Metabolism of atenolol in man. 1. The disposition and metabolism of 1-(4-carbamoyl[14C]methylphenoxy)-3-isopropylaminopan-2-ol (atenolol, Tenormin) has been studied in man following oral and intravenous doses. 2. Approx. 50% of an oral dose was eliminated in urine; the major radiolabelled component was atenolol (approx. 90%). Faecal extracts also contained largely unchanged atenolol, with small amounts of more polar metabolites. Biliary excretion of atenolol and its metabolites is not a major route of elimination in man. Metabolism of the compound is not extensive and route-dependent modes of metabolism do not appear to complicate the position. 3. Atenolol appeared to be the only major radiolabelled component in blood. 4. Oral doses of atenolol are incompletely absorbed (range 46-62%), even when formulated as a solution. 5. 1-[4-(C-Carbamoylhydroxymethyl)phenoxy]-3-isopropylaminopropan-2-ol was a minor urinary metabolite, which has only one tenth the activity of the parent compound as a beta-adrenergic blocking agent in the rat. 6. Pharmacological activity in man appears to be due to atenolol alone."}
{"id": "PMID:27022", "title": "On the evolution of an oligocephalic enzyme. glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains of Salmonella typhimurium.", "content": "(1) A procedure has been described for the purification of two glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains TAX6trpR782 and trpAB1653trpR782 of Salmonella typhimurium. (2) The native enzymes tend to aggregate forming polymers of molecular weights 333,000 in the case of TAXtrpR782 and 220,000 and larger than 1X10(6) in the case of trpAB1653trpR782. In the presence of sodium dodecyl sulfate the polymer of trpAB1653trpR782 dissociates into a single component with molecular weight of 72,000. (3) In contrast to anthranilate phosphoribosyltransferase of the wild type component II, the glutamine-chorismate-amidotransferase-free proteins do not complex with component I. They do however show catalytical similarities with the wild type with respect to anthranilate phosphoribosyltransferase activity.", "contents": "On the evolution of an oligocephalic enzyme. glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains of Salmonella typhimurium. (1) A procedure has been described for the purification of two glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains TAX6trpR782 and trpAB1653trpR782 of Salmonella typhimurium. (2) The native enzymes tend to aggregate forming polymers of molecular weights 333,000 in the case of TAXtrpR782 and 220,000 and larger than 1X10(6) in the case of trpAB1653trpR782. In the presence of sodium dodecyl sulfate the polymer of trpAB1653trpR782 dissociates into a single component with molecular weight of 72,000. (3) In contrast to anthranilate phosphoribosyltransferase of the wild type component II, the glutamine-chorismate-amidotransferase-free proteins do not complex with component I. They do however show catalytical similarities with the wild type with respect to anthranilate phosphoribosyltransferase activity."}
{"id": "PMID:27028", "title": "[Analytical data of flunitrazepam (rohypnol), a new benzodiazepine-derivative, in special consideration of its metabolites (author's transl)].", "content": "The article describes analytical data (TLC, GLC, IR, UV and MS) of flunitrazepam, 7-amino-flunitrazepam, desmethylflunitrazepam, 3-hydroxyflunitrazepam, 7-amino-desmethyl-flunitrazepam and many other benzodiazepine-derivatives, especially aminobenzophenones. Also extraction from biological specimen is reported.", "contents": "[Analytical data of flunitrazepam (rohypnol), a new benzodiazepine-derivative, in special consideration of its metabolites (author's transl)]. The article describes analytical data (TLC, GLC, IR, UV and MS) of flunitrazepam, 7-amino-flunitrazepam, desmethylflunitrazepam, 3-hydroxyflunitrazepam, 7-amino-desmethyl-flunitrazepam and many other benzodiazepine-derivatives, especially aminobenzophenones. Also extraction from biological specimen is reported."}
{"id": "PMID:27046", "title": "[On the distribution of myxobacteria in the temperate South America (author's transl)].", "content": "60 soil samples from Southern Chile, mainly from forests and grassland, yielded six species of myxobacteria. In forest soils Myxococcus coralloides and Myxococcus fulvus occur frequently, in grassland soils Myxococcus coralloides and Archangium gephyra are predominating. Myxococcus virescens, Melittangium lichenicola, and Cytobacter fuscus have been observed rarely. It is pointed out that due to climate factors a high soil acidity causes the low nuber of myxobacter species. A comparison with the number of species in substrates from important plant formations over various climates is given.", "contents": "[On the distribution of myxobacteria in the temperate South America (author's transl)]. 60 soil samples from Southern Chile, mainly from forests and grassland, yielded six species of myxobacteria. In forest soils Myxococcus coralloides and Myxococcus fulvus occur frequently, in grassland soils Myxococcus coralloides and Archangium gephyra are predominating. Myxococcus virescens, Melittangium lichenicola, and Cytobacter fuscus have been observed rarely. It is pointed out that due to climate factors a high soil acidity causes the low nuber of myxobacter species. A comparison with the number of species in substrates from important plant formations over various climates is given."}
{"id": "PMID:27047", "title": "[Neuraminidase activity of nonpathogenic Neisseria].", "content": "It was revealed earlier by the authors that N. meningitidis of the principal serological groups A, B, and C possessed neuraminidase activity. In the present work it was shown that this sign was genus-specific, and that this property was also possessed by the representatives of nonpathogenic neisseria habituating in the nasopharynx, However, the enzymatic activity in nonpathogenic neisseria was less pronounced than in meningococci, and required more prolonged contact of the enzymatic-substrate mixture for its detection. There was revealed a direct relationship between the neuraminidase activity and the growth phase of the microorganisms, whose maximum coincided with the exponential phase of bacterial growth, this apparently being associated with the extracellular character of its origin.", "contents": "[Neuraminidase activity of nonpathogenic Neisseria]. It was revealed earlier by the authors that N. meningitidis of the principal serological groups A, B, and C possessed neuraminidase activity. In the present work it was shown that this sign was genus-specific, and that this property was also possessed by the representatives of nonpathogenic neisseria habituating in the nasopharynx, However, the enzymatic activity in nonpathogenic neisseria was less pronounced than in meningococci, and required more prolonged contact of the enzymatic-substrate mixture for its detection. There was revealed a direct relationship between the neuraminidase activity and the growth phase of the microorganisms, whose maximum coincided with the exponential phase of bacterial growth, this apparently being associated with the extracellular character of its origin."}
{"id": "PMID:27048", "title": "[Study of hemosensitization characteristics for the purpose of standardizing erythrocyte flagellin diagnostica].", "content": "The work is devoted to the study of conditions required for the purpose of creation of standard and the most active preparations of erythrocytic H-diagnostic agents. The dependence of binding of the H-antigen by erythrocytes on the pH and the ionic power of the medium was investigated. It was demonstrated that in the process of erythrocyte sensitization with flagellin of great importance were electrostatic, hydrogen, and hydrophobic powers.", "contents": "[Study of hemosensitization characteristics for the purpose of standardizing erythrocyte flagellin diagnostica]. The work is devoted to the study of conditions required for the purpose of creation of standard and the most active preparations of erythrocytic H-diagnostic agents. The dependence of binding of the H-antigen by erythrocytes on the pH and the ionic power of the medium was investigated. It was demonstrated that in the process of erythrocyte sensitization with flagellin of great importance were electrostatic, hydrogen, and hydrophobic powers."}
{"id": "PMID:27049", "title": "[Method of culturing typhoid microorganisms with automatic regulation of glucose feed].", "content": "A system of oxygen-glucose inverse relationship is not acceptable for cultivation of typhoid bacilli with a high reproductive rate and glucose utilization. The elaborated method of automatic glucose supply during typhoid bacilli cultivation permits to lead the process under the optimal conditions by pH and the residual glucose concentration.", "contents": "[Method of culturing typhoid microorganisms with automatic regulation of glucose feed]. A system of oxygen-glucose inverse relationship is not acceptable for cultivation of typhoid bacilli with a high reproductive rate and glucose utilization. The elaborated method of automatic glucose supply during typhoid bacilli cultivation permits to lead the process under the optimal conditions by pH and the residual glucose concentration."}
{"id": "PMID:27050", "title": "[Acid-base balance during dosed fasting of schizophrenic patients with residual manifestations of organic lesions of the central nervous system].", "content": "The indices of acid-alkaline blood balance was studied in the dynamics of dosed hungering in 29 patients with sluggish schizophrenia and 16 patients with residual signs oforganic lesions of the CNS. There were differences in the pH index, standard and buffer bicarbonates alkaline deficiency which indicated to different degrees of acidosis in this group of patients. Significant differences in the acid-alkaline indices during hunger were seen in the different groups of patients depending upon the existence or absence of hypothalamic disorders (without consideration of their nosological affinity). The existence of hypothalamic disorders requires a more careful consideration when prescribing hunger therapy (the first session should not exceed 10-14 days).", "contents": "[Acid-base balance during dosed fasting of schizophrenic patients with residual manifestations of organic lesions of the central nervous system]. The indices of acid-alkaline blood balance was studied in the dynamics of dosed hungering in 29 patients with sluggish schizophrenia and 16 patients with residual signs oforganic lesions of the CNS. There were differences in the pH index, standard and buffer bicarbonates alkaline deficiency which indicated to different degrees of acidosis in this group of patients. Significant differences in the acid-alkaline indices during hunger were seen in the different groups of patients depending upon the existence or absence of hypothalamic disorders (without consideration of their nosological affinity). The existence of hypothalamic disorders requires a more careful consideration when prescribing hunger therapy (the first session should not exceed 10-14 days)."}
{"id": "PMID:27051", "title": "Polymorphism of the cobalt-activated acylase in human tissues.", "content": "A method was elaborated for obtaining polyacrylamide gel zymograms of the cobalt-activated acylase after electrophoresis. Two fractions of the acylase showing activity towards N-chloroacetyl-gamma-L-glutamyl-beta-naphthylamide were found in human kidney, liver and intestine. The two fractions isolated from liver differ in substrate specificity, heat resistance, response to metal ions, inhibition by deaminated dipeptides, and in molecular weight. They differ also from other N-acylamino acid amidohydrolases: aminoacylase (EC 3.5.1.14) and aspartoacylase (EC 3.5.1.15).", "contents": "Polymorphism of the cobalt-activated acylase in human tissues. A method was elaborated for obtaining polyacrylamide gel zymograms of the cobalt-activated acylase after electrophoresis. Two fractions of the acylase showing activity towards N-chloroacetyl-gamma-L-glutamyl-beta-naphthylamide were found in human kidney, liver and intestine. The two fractions isolated from liver differ in substrate specificity, heat resistance, response to metal ions, inhibition by deaminated dipeptides, and in molecular weight. They differ also from other N-acylamino acid amidohydrolases: aminoacylase (EC 3.5.1.14) and aspartoacylase (EC 3.5.1.15)."}
{"id": "PMID:27052", "title": "[Measurements and calculations on aglycon liberation from highly masked CMT selectines with beta-glucuronidase at pH 6. Realization of the principle of transport form-activity in anti-cancer drugs: theory of selectivity].", "content": "The authors describe methods and results on the aglycon liberation from several glucuronides using beta-flucuronidase in vitro. The glucuronides examined are prototypes of new potent anticancer drugs (so-called CMT selectines). Basing on the knowledge of the values and parameters involved theoretical considerations result in evaluation of the anticipated selective action of CMT selectines in artificially hyperacidified cancer tissues compared to normal tissues. The equations derived from certain mathematical simplifications are presented. The calculated high selectivity S approximately 20 can only be realized in vivo if the \"masking index\" s as to toxic action and renal clearance of a chosen CMT selectine is greater than 20. In fact, the hitherto known CMT selectines exhibit sufficiently high masking indices that the realization of a true transportation form/active form principle using different cancerotoxic agents as aglycones can be assumed.", "contents": "[Measurements and calculations on aglycon liberation from highly masked CMT selectines with beta-glucuronidase at pH 6. Realization of the principle of transport form-activity in anti-cancer drugs: theory of selectivity]. The authors describe methods and results on the aglycon liberation from several glucuronides using beta-flucuronidase in vitro. The glucuronides examined are prototypes of new potent anticancer drugs (so-called CMT selectines). Basing on the knowledge of the values and parameters involved theoretical considerations result in evaluation of the anticipated selective action of CMT selectines in artificially hyperacidified cancer tissues compared to normal tissues. The equations derived from certain mathematical simplifications are presented. The calculated high selectivity S approximately 20 can only be realized in vivo if the \"masking index\" s as to toxic action and renal clearance of a chosen CMT selectine is greater than 20. In fact, the hitherto known CMT selectines exhibit sufficiently high masking indices that the realization of a true transportation form/active form principle using different cancerotoxic agents as aglycones can be assumed."}
{"id": "PMID:27053", "title": "[Effect of rapid changes of the oxygenation state and other external parameters on the long-term behavior of the energy metabolism in the erythrocyte].", "content": "The red blood cell when transported through the circulatory system is exposed to a steady (approximately periodical) change of environmental conditions causing a permanent fluctuation of its important metabolic parameters. In a simple theoretical model it is demonstrated that a rapid oscillation of such parameters may stabilize a metabolic state which will collapse when this oscillation breaks off. The hypothesis is advanced that parameter oscillations caused by the physiological function of the red blood cell may be of importance for the maintenance of its energy metabolism and that the break-off of these oscillations may be a potential cause for the metabolic collapse, e.g. in stored blood.", "contents": "[Effect of rapid changes of the oxygenation state and other external parameters on the long-term behavior of the energy metabolism in the erythrocyte]. The red blood cell when transported through the circulatory system is exposed to a steady (approximately periodical) change of environmental conditions causing a permanent fluctuation of its important metabolic parameters. In a simple theoretical model it is demonstrated that a rapid oscillation of such parameters may stabilize a metabolic state which will collapse when this oscillation breaks off. The hypothesis is advanced that parameter oscillations caused by the physiological function of the red blood cell may be of importance for the maintenance of its energy metabolism and that the break-off of these oscillations may be a potential cause for the metabolic collapse, e.g. in stored blood."}
{"id": "PMID:27056", "title": "Reversibility of the blood-brain barrier dysfunction induced by acute hypertension.", "content": "An acute hypertensive episode of short duration (less than 3 min) induced by i.v. injection of angiotensin in rats resulted in a blood-brain barrier dysfunction that was rapidly reversible. Thus, no macroscopic extravasation was seen when Evans blue was given 10 or 20 min after angiotensin. A faint fluorescence (Evans blue-albumin) was seen in the walls of some intracerebral arterioles in a few rats given the tracer 10 min after angiotensin.", "contents": "Reversibility of the blood-brain barrier dysfunction induced by acute hypertension. An acute hypertensive episode of short duration (less than 3 min) induced by i.v. injection of angiotensin in rats resulted in a blood-brain barrier dysfunction that was rapidly reversible. Thus, no macroscopic extravasation was seen when Evans blue was given 10 or 20 min after angiotensin. A faint fluorescence (Evans blue-albumin) was seen in the walls of some intracerebral arterioles in a few rats given the tracer 10 min after angiotensin."}
{"id": "PMID:27055", "title": "[Adult metachromatic leucodystrophy (author's transl)].", "content": "A new adult case of metachromatic leucodystrophy (MLD) is reported. The earliest clinical signs are psychiatric in contra-distinction with the prevalent neurological signs observed in infantile or juvenile MLD. Although the occurrence of psychiatric features in adolescents or adults does not at first suggest MLD, it is easy to ascertain the diagnosis by combining the enzymatic assay of arylsulfatase A on leucocytes or cultured fibroblasts with the morphological study of nerve bundles. Such a discovery has of course a major importance in genetic counselling.", "contents": "[Adult metachromatic leucodystrophy (author's transl)]. A new adult case of metachromatic leucodystrophy (MLD) is reported. The earliest clinical signs are psychiatric in contra-distinction with the prevalent neurological signs observed in infantile or juvenile MLD. Although the occurrence of psychiatric features in adolescents or adults does not at first suggest MLD, it is easy to ascertain the diagnosis by combining the enzymatic assay of arylsulfatase A on leucocytes or cultured fibroblasts with the morphological study of nerve bundles. Such a discovery has of course a major importance in genetic counselling."}
{"id": "PMID:27060", "title": "Measurement of cerebral blood flow in the fetal lamb with a note on the flow-distribution.", "content": "The cerebral blood flow was measured in the acutely exteriorized fetal lamb by 133Xenon washout and microsphere distribution techniques. The measurements were performed at different blood gas levels. Regional cerebral blood flow was calculated from the microsphere distribution for five different parts of the brain. This gave estimates for blood flow in both the grey and white matter of the hemispheres, which were in close agreement with the cerebral blood flow estimated by the 133Xe washout technique. The microsphere distribution shows that the fetal cerebral hemisphere has a low blood flow compared to the basel parts of the brain and that this difference is increased during hypoxia and hypercarbia.", "contents": "Measurement of cerebral blood flow in the fetal lamb with a note on the flow-distribution. The cerebral blood flow was measured in the acutely exteriorized fetal lamb by 133Xenon washout and microsphere distribution techniques. The measurements were performed at different blood gas levels. Regional cerebral blood flow was calculated from the microsphere distribution for five different parts of the brain. This gave estimates for blood flow in both the grey and white matter of the hemispheres, which were in close agreement with the cerebral blood flow estimated by the 133Xe washout technique. The microsphere distribution shows that the fetal cerebral hemisphere has a low blood flow compared to the basel parts of the brain and that this difference is increased during hypoxia and hypercarbia."}
{"id": "PMID:27057", "title": "Identification of beta-adrenoceptors and histamine receptors in the cat nasal vasculature.", "content": "The responses of the nasal capacitance vessels of the cat were recorded following intra-arterial injections of beta-adrenoceptor agonists and histamine H1-and H2-receptor agonists. Isoprenaline evoked vasodilation and propranolol (beta-adrenoceptor antagonist) caused a parallel shift to the right of the isoprenaline log dose-response curve. Histamine, 2-(2-aminoethyl)pyridine (H1-agonist) and 4-methylhistamine (predominantly H2-agonist) all evoked vasodilation. Metiamide (H2-antagonist) produced a further small parallel shift to the right of the histamine log dose-response curve after the administration of mepyramine (H1-antagonist). It is concluded that the nasal capacitance vessels of the cat contain beta 2-adrenoceptors and H1-and H2-histamine receptors.", "contents": "Identification of beta-adrenoceptors and histamine receptors in the cat nasal vasculature. The responses of the nasal capacitance vessels of the cat were recorded following intra-arterial injections of beta-adrenoceptor agonists and histamine H1-and H2-receptor agonists. Isoprenaline evoked vasodilation and propranolol (beta-adrenoceptor antagonist) caused a parallel shift to the right of the isoprenaline log dose-response curve. Histamine, 2-(2-aminoethyl)pyridine (H1-agonist) and 4-methylhistamine (predominantly H2-agonist) all evoked vasodilation. Metiamide (H2-antagonist) produced a further small parallel shift to the right of the histamine log dose-response curve after the administration of mepyramine (H1-antagonist). It is concluded that the nasal capacitance vessels of the cat contain beta 2-adrenoceptors and H1-and H2-histamine receptors."}
{"id": "PMID:27061", "title": "Alprenolol fails to antagonize the metabolic changes following repeated thyroxine injections in the rat.", "content": "Repeated injections of rat with 1-thyroxine (50 microgram/kg daily for 5 five-day weeks) retarded the weight gain of the animals and increased the absolute and relative size of the heart, adrenals and interscapular brown adipose tissue. In the myocardium and thigh muscle, thyroxine treatment resulted in elevated activity of oxidative enzymes, succinate dehydrogenase, malate dehydrogenase and citrate synthase, while the activities of glycolytic enzymes remained unchanged. Glycogen content of the heart was decreased following thyroxine regime. In the brown fat, on the other hand, thyroxine injections resulted in a reduction of the activity of oxidative enzymes. This reduction can be accounted for by the decreased protein (enzyme) content of the tissue due to deposition of fat. Furthermore, thyroxine treatment delayed the body cooling of the rats swimming in water at 25 degrees C and enhanced hyperthermic response to injected noradrenaline. All these changes, which were not observable in rats treated with daily alprenolol (20 mg/kg) injections, were as pronounced in rats injected with alprenolol together with thyroxine as in rats injected with thyroxine only. It is concluded that beta blockers do not antagonize the metabolic changes due to hyperthyroidism.", "contents": "Alprenolol fails to antagonize the metabolic changes following repeated thyroxine injections in the rat. Repeated injections of rat with 1-thyroxine (50 microgram/kg daily for 5 five-day weeks) retarded the weight gain of the animals and increased the absolute and relative size of the heart, adrenals and interscapular brown adipose tissue. In the myocardium and thigh muscle, thyroxine treatment resulted in elevated activity of oxidative enzymes, succinate dehydrogenase, malate dehydrogenase and citrate synthase, while the activities of glycolytic enzymes remained unchanged. Glycogen content of the heart was decreased following thyroxine regime. In the brown fat, on the other hand, thyroxine injections resulted in a reduction of the activity of oxidative enzymes. This reduction can be accounted for by the decreased protein (enzyme) content of the tissue due to deposition of fat. Furthermore, thyroxine treatment delayed the body cooling of the rats swimming in water at 25 degrees C and enhanced hyperthermic response to injected noradrenaline. All these changes, which were not observable in rats treated with daily alprenolol (20 mg/kg) injections, were as pronounced in rats injected with alprenolol together with thyroxine as in rats injected with thyroxine only. It is concluded that beta blockers do not antagonize the metabolic changes due to hyperthyroidism."}
{"id": "PMID:27064", "title": "Acute and long-term salt depletion and beta-blockade: plasma renin activity response and its relation to blood pressure reduction in long-term treatment.", "content": "The changes in plasma renin activity (PRA) during short-term salt depletion (and peroral furosemide on the first day) and after bolus injection of propranolol were compared to the change during long-term treatment with diuretic and with propranolol in 19 patients with benign primary hypertension. A highly significant correlation was found between PRA on short-term and long-term salt depletion (r=0.02). A highly significant correlation was likewise found between initial PRA and decrement of PRA after bolus injection of or long-term treatment with propranolol. Only a weak inverse correlation was found between PRA reached during short-term salt depletion or long-term diuretic treatment and the fall in diastolic BP during long-term treatment (r=0.60). No significant correlation was found between decrease in PRA on propranolol (bolus/long-term) and diastolic BP reduction. It is concluded that the short-term PRA response to salt depletion and propranolol in the individual patient gives a good prediction of the PRA level on long-term diuretic or propranolol treatment, but is of no value in predicting the BP reduction during treatment.", "contents": "Acute and long-term salt depletion and beta-blockade: plasma renin activity response and its relation to blood pressure reduction in long-term treatment. The changes in plasma renin activity (PRA) during short-term salt depletion (and peroral furosemide on the first day) and after bolus injection of propranolol were compared to the change during long-term treatment with diuretic and with propranolol in 19 patients with benign primary hypertension. A highly significant correlation was found between PRA on short-term and long-term salt depletion (r=0.02). A highly significant correlation was likewise found between initial PRA and decrement of PRA after bolus injection of or long-term treatment with propranolol. Only a weak inverse correlation was found between PRA reached during short-term salt depletion or long-term diuretic treatment and the fall in diastolic BP during long-term treatment (r=0.60). No significant correlation was found between decrease in PRA on propranolol (bolus/long-term) and diastolic BP reduction. It is concluded that the short-term PRA response to salt depletion and propranolol in the individual patient gives a good prediction of the PRA level on long-term diuretic or propranolol treatment, but is of no value in predicting the BP reduction during treatment."}
{"id": "PMID:27069", "title": "Stereochemical studies of hydrogen incorporation from nucleotides with fatty acid synthetase from Brevibacterium ammoniagenes.", "content": "The biosynthesis of fatty acids from malonyl-CoA and acetyl-CoA was investigated with an enzyme preparation which was purified 100-fold from Brevibacterium ammoniagenes. Fatty acids synthesized in the presence of D2O and stereospecifically deuterated NADPH and NADH were isolated and analyzed by mass chromatography to examine the localization of deuterium in the molecule. The following results were obtained: 1) HB hydrogen of NADPH was used for beta-ketoacyl reductase. 2) HB hydrogen of NADH was used for enoyl reductase. 3) Hydrogen atoms from water were found on the even-numbered methylene carbon atoms (2-hydrogen atoms per carbon atom) and some were also found on the odd-numbered methylene carbon. 4) Hydrogen atoms from NADPH were found on odd-numbered methylene carbon atoms (1-hydrogen per carbon). 5) Hydrogen atoms from NADH were also found on the odd-numbered methylene carbon atoms, but the number of incorporated hydrogen atoms was less than expected. The exchange of HB hydrogen of NADH with water catalyzed by enoyl reductase was suspected. 6) The exchange of methylene hydrogen atoms of malonyl-CoA with proton of water was suggested by 13C NMR analysis.", "contents": "Stereochemical studies of hydrogen incorporation from nucleotides with fatty acid synthetase from Brevibacterium ammoniagenes. The biosynthesis of fatty acids from malonyl-CoA and acetyl-CoA was investigated with an enzyme preparation which was purified 100-fold from Brevibacterium ammoniagenes. Fatty acids synthesized in the presence of D2O and stereospecifically deuterated NADPH and NADH were isolated and analyzed by mass chromatography to examine the localization of deuterium in the molecule. The following results were obtained: 1) HB hydrogen of NADPH was used for beta-ketoacyl reductase. 2) HB hydrogen of NADH was used for enoyl reductase. 3) Hydrogen atoms from water were found on the even-numbered methylene carbon atoms (2-hydrogen atoms per carbon atom) and some were also found on the odd-numbered methylene carbon. 4) Hydrogen atoms from NADPH were found on odd-numbered methylene carbon atoms (1-hydrogen per carbon). 5) Hydrogen atoms from NADH were also found on the odd-numbered methylene carbon atoms, but the number of incorporated hydrogen atoms was less than expected. The exchange of HB hydrogen of NADH with water catalyzed by enoyl reductase was suspected. 6) The exchange of methylene hydrogen atoms of malonyl-CoA with proton of water was suggested by 13C NMR analysis."}
{"id": "PMID:27072", "title": "Studies on the function of the activator of sulphatase A.", "content": "The activator of sulphatase A is necessary for the enzymic degradation of sulphatides to cerebrosides at ionic concentrations in the physiological range (1). Activation is probably due to the reversible formation of a one-to-one complex between activator and sulphatides (1,2). Formation of this complex is partly inhibited by cerebrosides due to competitive binding (2), as well as by phospholipids (e.g. lecithin or phosphatidylserine). Inhibition of the complex formation between activator and sulphatides by cerebrosides and phosphatidyl-serine depends on the concentration of the lipids and is of the same order of magnitude as the inhibition (by these lipids) of the enzymic degradation of sulphatides in the presence of activator (1). Moreover the degradation rate of sulphatides increases with the concentration of activator-sulphatide complex in the reaction mixture (1) indicating that the activator-sulphatide complex is the substrate for the enzyme in the degradation of sulphatides by sulphatase A.", "contents": "Studies on the function of the activator of sulphatase A. The activator of sulphatase A is necessary for the enzymic degradation of sulphatides to cerebrosides at ionic concentrations in the physiological range (1). Activation is probably due to the reversible formation of a one-to-one complex between activator and sulphatides (1,2). Formation of this complex is partly inhibited by cerebrosides due to competitive binding (2), as well as by phospholipids (e.g. lecithin or phosphatidylserine). Inhibition of the complex formation between activator and sulphatides by cerebrosides and phosphatidyl-serine depends on the concentration of the lipids and is of the same order of magnitude as the inhibition (by these lipids) of the enzymic degradation of sulphatides in the presence of activator (1). Moreover the degradation rate of sulphatides increases with the concentration of activator-sulphatide complex in the reaction mixture (1) indicating that the activator-sulphatide complex is the substrate for the enzyme in the degradation of sulphatides by sulphatase A."}
{"id": "PMID:27085", "title": "Renal consequences of narcotic abuse.", "content": "Heroin addiction is associated with several severe and occasionally fatal renal complications. Acute renal failure consequent to rhabdomyolysis and myoglobinuria, when treated supportively, carries a good prognosis. Staphylococcal or other bacterial septicemia may in itself prove fatal and is associated with a proliferative immune complex, acute glomerulonephritis, which generally follows the course and prognosis of septicemia. The necrotizing angiitis reported in heroin addicts still is largely undefined. Focal and segmental glomerular sclerosis is the most common pathologic finding in the syndrome of heroin-associated nephropathy (HAN). Typically, HAN presents with massive proteinuria and progresses rapidly to renal failure. Presumptive evidence supports the premise that heroin or its vehicles elicits immunologically mediated renal damage. The antigen still is unidentified. Removing the antigenic challenge by stopping heroin injection apparently interdicts the progression of renal disease. Renal transplantation can be effectively accomplished in patients with HAN without early recurrence if patients discontinue the use of heroin.", "contents": "Renal consequences of narcotic abuse. Heroin addiction is associated with several severe and occasionally fatal renal complications. Acute renal failure consequent to rhabdomyolysis and myoglobinuria, when treated supportively, carries a good prognosis. Staphylococcal or other bacterial septicemia may in itself prove fatal and is associated with a proliferative immune complex, acute glomerulonephritis, which generally follows the course and prognosis of septicemia. The necrotizing angiitis reported in heroin addicts still is largely undefined. Focal and segmental glomerular sclerosis is the most common pathologic finding in the syndrome of heroin-associated nephropathy (HAN). Typically, HAN presents with massive proteinuria and progresses rapidly to renal failure. Presumptive evidence supports the premise that heroin or its vehicles elicits immunologically mediated renal damage. The antigen still is unidentified. Removing the antigenic challenge by stopping heroin injection apparently interdicts the progression of renal disease. Renal transplantation can be effectively accomplished in patients with HAN without early recurrence if patients discontinue the use of heroin."}
{"id": "PMID:27086", "title": "The effect of cyclophosphamide and methotrexate on the 'field effect' or unresponsiveness observed in the rat and mouse GvHR.", "content": "The Field effect is the decreased biological response to a second challenge in the graft versus host reaction (GvHR). Treatment of recipeint rats or mice during the initial GvHR by methotrexate or cyclophosphamide effected the secondary unresponsivienss. Methotrexate and cyclophosphamide demonstrated different temporal responses indicating different mechanisms of their immunosuppresdive activities.", "contents": "The effect of cyclophosphamide and methotrexate on the 'field effect' or unresponsiveness observed in the rat and mouse GvHR. The Field effect is the decreased biological response to a second challenge in the graft versus host reaction (GvHR). Treatment of recipeint rats or mice during the initial GvHR by methotrexate or cyclophosphamide effected the secondary unresponsivienss. Methotrexate and cyclophosphamide demonstrated different temporal responses indicating different mechanisms of their immunosuppresdive activities."}
{"id": "PMID:27087", "title": "Conditions for the formation of cyclic compounds between pyridoxal phosphate and 5-hydroxytryptamine or 5-hydroxytryptophan.", "content": "5-Hydroxytryptamine (5HT) and 5-hydroxytryptophan (5HTP) form cyclic compounds (probably of the tetrahydro-beta-carboline type) with pyridoxal phosphate (PLP). In the first step of reaction a Schiff's base is formed; during incubation it is transformed into a cyclic compound with a maximum absorption spectrum at 330 nm. The degree of cyclization depends on pH and substrate concentrations. One mole of 5HT or 5HTP reacts with one mole of coenzyme. The velocity of cyclization increased with an excess of either 5HT (5HTP) or PLP, without any change in the mole to mole ratio. The formation of cyclic compounds was confirmed by the use of isotopes, separation from substrates being achieved by high-voltage electrophoresis.", "contents": "Conditions for the formation of cyclic compounds between pyridoxal phosphate and 5-hydroxytryptamine or 5-hydroxytryptophan. 5-Hydroxytryptamine (5HT) and 5-hydroxytryptophan (5HTP) form cyclic compounds (probably of the tetrahydro-beta-carboline type) with pyridoxal phosphate (PLP). In the first step of reaction a Schiff's base is formed; during incubation it is transformed into a cyclic compound with a maximum absorption spectrum at 330 nm. The degree of cyclization depends on pH and substrate concentrations. One mole of 5HT or 5HTP reacts with one mole of coenzyme. The velocity of cyclization increased with an excess of either 5HT (5HTP) or PLP, without any change in the mole to mole ratio. The formation of cyclic compounds was confirmed by the use of isotopes, separation from substrates being achieved by high-voltage electrophoresis."}
{"id": "PMID:27090", "title": "Effect of prior antibiotic therapy on concentrations of bacteria in CSF.", "content": "A prospective study was done to determine the effect of prior antibiotic therapy on concentrations of bacteria in CSF at the time of diagnosis. Concentrations of Haemophilus influenzae type b in CSF of partially treated patients were significantly smaller than in CSF of untreated patients. This was also true of patients with meningococcal meningitis, but no difference was observed between patients with pneumococcal meningitis. The identification of H influenzae by Gram stain of CSF was significantly decreased by prior antibiotic therapy. Measurable levels of antibiotic (penicillins, aminoglycosides) were present in CSF of ten of 23 patients. Two partially treated patients were diagnosed by detection of meningococcal antigen in CSF by counterimmunoelectrophoresis although cultures of CSF were sterile. Both of these patients had measurable levels of penicillin in CSF. These data indicate that prior antibiotic therapy significantly decreases the concentration of H influenzae type b and meningococcus in CSF and therefore decreases the usefulness of CSF Gram stain. Partial therapy may sterilize the CSF of some patients.", "contents": "Effect of prior antibiotic therapy on concentrations of bacteria in CSF. A prospective study was done to determine the effect of prior antibiotic therapy on concentrations of bacteria in CSF at the time of diagnosis. Concentrations of Haemophilus influenzae type b in CSF of partially treated patients were significantly smaller than in CSF of untreated patients. This was also true of patients with meningococcal meningitis, but no difference was observed between patients with pneumococcal meningitis. The identification of H influenzae by Gram stain of CSF was significantly decreased by prior antibiotic therapy. Measurable levels of antibiotic (penicillins, aminoglycosides) were present in CSF of ten of 23 patients. Two partially treated patients were diagnosed by detection of meningococcal antigen in CSF by counterimmunoelectrophoresis although cultures of CSF were sterile. Both of these patients had measurable levels of penicillin in CSF. These data indicate that prior antibiotic therapy significantly decreases the concentration of H influenzae type b and meningococcus in CSF and therefore decreases the usefulness of CSF Gram stain. Partial therapy may sterilize the CSF of some patients."}
{"id": "PMID:27091", "title": "Effect of bile acids and pH on the release of enteropeptidase in man.", "content": "Bile acids increase the release of human enteropeptidase as well as other brush-border enzymes (alkaline phosphatase, leucine aminopeptidase) from duodenal mucosa, as had been shown earlier in experimental animals. The action of bile acids is independent of their known enhancing effect on enteropeptidase activity. The pH of duodenal juice is an important, hitherto unrecognized, factor in the release mechanism of brush-border enzymes. All of the above enzymes tested were released to a markedly greater extent at pH 8.2 than 6.3, regardless of the presence or absence of bile acid. Contrary to some results obtained with animal tissue, by other investigators, our experiments with human duodenal mucosa indicate that enteropeptidase, under all conditions tested, is released at a rate considerably greater than that for alkaline phosphatase or leucine aminopeptidase. The looser association of enteropeptidase with cellular components relative to that of other brush-border enzymes, as indicated by our observations, may be related to the unique function of enteropeptidase as the trigger enzyme of protein digestion.", "contents": "Effect of bile acids and pH on the release of enteropeptidase in man. Bile acids increase the release of human enteropeptidase as well as other brush-border enzymes (alkaline phosphatase, leucine aminopeptidase) from duodenal mucosa, as had been shown earlier in experimental animals. The action of bile acids is independent of their known enhancing effect on enteropeptidase activity. The pH of duodenal juice is an important, hitherto unrecognized, factor in the release mechanism of brush-border enzymes. All of the above enzymes tested were released to a markedly greater extent at pH 8.2 than 6.3, regardless of the presence or absence of bile acid. Contrary to some results obtained with animal tissue, by other investigators, our experiments with human duodenal mucosa indicate that enteropeptidase, under all conditions tested, is released at a rate considerably greater than that for alkaline phosphatase or leucine aminopeptidase. The looser association of enteropeptidase with cellular components relative to that of other brush-border enzymes, as indicated by our observations, may be related to the unique function of enteropeptidase as the trigger enzyme of protein digestion."}
{"id": "PMID:27092", "title": "The pediatric corner: the varied manifestations of Crohn's disease in children and adolescents.", "content": "Thirty children less than 15 years of age with Crohn's disease are reported. The mean age of onset was nine years and five months. Delay in diagnosis may stem from the varying modes of presentation. The mean delay in diagnosis was two years. Chronic diarrhea and/or recurrent abdominal pain associated with extraintestinal manifestations, particularly abnormalities of growth and development suggests the possibility of Crohn's disease in the pediatric age group. Involvement of the terminal ileum occurred in 29 of the 30 patients. In addition, colonic disease occurred in 13 and jejunal involvement in one. Four patients presented with an acute onset of their disease. A favorable response to either medical or surgical therapy occurred in all four. Twenty-six patients had an insidious onset and tended to have a chronic course despite either medical and/or surgical therapy. Thirteen patients had an intestinal resection, with recurrence occurring in three from 1-4 years postoperatively. To date there has been one death.", "contents": "The pediatric corner: the varied manifestations of Crohn's disease in children and adolescents. Thirty children less than 15 years of age with Crohn's disease are reported. The mean age of onset was nine years and five months. Delay in diagnosis may stem from the varying modes of presentation. The mean delay in diagnosis was two years. Chronic diarrhea and/or recurrent abdominal pain associated with extraintestinal manifestations, particularly abnormalities of growth and development suggests the possibility of Crohn's disease in the pediatric age group. Involvement of the terminal ileum occurred in 29 of the 30 patients. In addition, colonic disease occurred in 13 and jejunal involvement in one. Four patients presented with an acute onset of their disease. A favorable response to either medical or surgical therapy occurred in all four. Twenty-six patients had an insidious onset and tended to have a chronic course despite either medical and/or surgical therapy. Thirteen patients had an intestinal resection, with recurrence occurring in three from 1-4 years postoperatively. To date there has been one death."}
{"id": "PMID:27093", "title": "Effect of a new antacid on basal and meal-stimulated gastric secretion.", "content": "Our study of the comparative neutralizing effectiveness of four antacids on the acidity and pH of the basal gastric secretion in 32 patients showed that using the conventional doses of two tablets of Rolaids, two tablets of Di-Gel, 15 ml. of Maalox liquid or two tablets of Conquel, they are equal in their acid neutralizing capacity. The duration of action for 45-60 minutes. Conquel, in a dose of two tablets, was a potent buffer for the peptone-meal stimulated secretion. The duration of action lasted for longer than two hours.", "contents": "Effect of a new antacid on basal and meal-stimulated gastric secretion. Our study of the comparative neutralizing effectiveness of four antacids on the acidity and pH of the basal gastric secretion in 32 patients showed that using the conventional doses of two tablets of Rolaids, two tablets of Di-Gel, 15 ml. of Maalox liquid or two tablets of Conquel, they are equal in their acid neutralizing capacity. The duration of action for 45-60 minutes. Conquel, in a dose of two tablets, was a potent buffer for the peptone-meal stimulated secretion. The duration of action lasted for longer than two hours."}
{"id": "PMID:27094", "title": "Granulomatous ileocolitis preceded by three years of pauciarticular arthritis.", "content": "The case of a 12-year old male is presented in whom pauciarticular arthritis preceded the clinical onset of granulomatous ileocolitis by three years. Before the onset of gastrointestinal symptoms, the patients' clinical diagnosis was juvenile rheumatoid arthritis. This case stresses the importance of including inflammatory bowel disease in the differential diagnosis of pauciarticular arthritis in children.", "contents": "Granulomatous ileocolitis preceded by three years of pauciarticular arthritis. The case of a 12-year old male is presented in whom pauciarticular arthritis preceded the clinical onset of granulomatous ileocolitis by three years. Before the onset of gastrointestinal symptoms, the patients' clinical diagnosis was juvenile rheumatoid arthritis. This case stresses the importance of including inflammatory bowel disease in the differential diagnosis of pauciarticular arthritis in children."}
{"id": "PMID:27097", "title": "The influence of maternal psychological stress on the fetus.", "content": "The effects of maternal agitation, induced by exposure to bright light, upon fetal well-being were studied in pregnant rhesus monkeys at 139 to 148 days of gestation. Fetuses were classified as \"healthy\" or \"asphyxiated\" according to their initial acid-base state. Following variable periods of maternal excitement, a decrease in heart rate and arterial oxygenation was seen in all fetuses. Recovery occurred more rapidly in the healthy group, after maternal sedation was achieved, either by removing the stimulus or by additional administration of pentobarbital, 5 to 20 mg. intravenously. The beneficial effects of meternal sedation on the fetus have thus been demonstrated.", "contents": "The influence of maternal psychological stress on the fetus. The effects of maternal agitation, induced by exposure to bright light, upon fetal well-being were studied in pregnant rhesus monkeys at 139 to 148 days of gestation. Fetuses were classified as \"healthy\" or \"asphyxiated\" according to their initial acid-base state. Following variable periods of maternal excitement, a decrease in heart rate and arterial oxygenation was seen in all fetuses. Recovery occurred more rapidly in the healthy group, after maternal sedation was achieved, either by removing the stimulus or by additional administration of pentobarbital, 5 to 20 mg. intravenously. The beneficial effects of meternal sedation on the fetus have thus been demonstrated."}
{"id": "PMID:27099", "title": "Gastric HCO3--secretion in the guinea pig.", "content": "Measurement of gastric intraluminal PCO2 and pH in the anesthetized guinea pig enabled simultaneous determination of total H+ and HCO3- gastric secretions. There was quantitative agreement between the release of CO2 and decrease in HCO3- after intragastric instillation of HCl. The basal rate of HCO3- secretion (approximately 40 mueq-h-1) was, in most cases, smaller than spontaneous H+ secretion, but gastric net secretory output was alkaline (HCO3- greater than H+) after inhibition of acid secretion with histamine H2-receptor antagonists (cimetidine 20 mg-kg-1 or metiamide 35 mg-kg-1). Carbachol (1-2 microgram-kg-1) stimulated secretion of both HCO3- and H+; only the latter response was sensitive to the histamine antagonists. Atropin (100 microgram-kg-1) blocked stimulation of HCO3- secretion but did not affect the basal output of HCO3-. An increase in HCO3- secretion was associated with an equivalent increase in net Na+ influx and an increase in the net influx of Cl- with H+ plus K+. Intragastric neutralization of H+ by HCO3- is likely to occur at the mucosal surface and may protect the mucosa from the damaging effects of intraluminal acid.", "contents": "Gastric HCO3--secretion in the guinea pig. Measurement of gastric intraluminal PCO2 and pH in the anesthetized guinea pig enabled simultaneous determination of total H+ and HCO3- gastric secretions. There was quantitative agreement between the release of CO2 and decrease in HCO3- after intragastric instillation of HCl. The basal rate of HCO3- secretion (approximately 40 mueq-h-1) was, in most cases, smaller than spontaneous H+ secretion, but gastric net secretory output was alkaline (HCO3- greater than H+) after inhibition of acid secretion with histamine H2-receptor antagonists (cimetidine 20 mg-kg-1 or metiamide 35 mg-kg-1). Carbachol (1-2 microgram-kg-1) stimulated secretion of both HCO3- and H+; only the latter response was sensitive to the histamine antagonists. Atropin (100 microgram-kg-1) blocked stimulation of HCO3- secretion but did not affect the basal output of HCO3-. An increase in HCO3- secretion was associated with an equivalent increase in net Na+ influx and an increase in the net influx of Cl- with H+ plus K+. Intragastric neutralization of H+ by HCO3- is likely to occur at the mucosal surface and may protect the mucosa from the damaging effects of intraluminal acid."}
{"id": "PMID:27100", "title": "Acetylsalicylic acid hydrolase of gastric mucosa.", "content": "Acetylsalicylic acid hydrolase activity of rabbit fundic gastric mucosa has been isolated from the soluble 100,000 X g supernate. The enzymatic activity was partially purified by ammonium sulfate precipitation. The Km for acetylsalicylate was 2 mM and pH optimum was 8.6. The activity was insensitive to ionic strength, slightly inhibited by inclusion of 100 mM Cl-, and demonstrated no requirement for Ca2+ or Mg2+. Acetylsalicylic acid esterase was markedly inhibited by sodium cholate and sodium dodecyl sulfate. The enzyme was insensitive to sulfhydryl reagents with the exception of p-chloromercuribenzenesulfonic acid, which markedly inhibited the enzyme. Diisopropyl fluorophosphate (DFP) inhibited enzymatic activity with a Ki of 9 X 10(-9)M. Eserine was also inhibitory with a Ki of 0.25 mM. Inhibition by DFP at low concentration and by eserine at millimolar concentrations suggests that this enzyme is related to the group of aliphatic esterases. Identification of potent inhibitors will enable studies to define the role of this enzyme with the use of experimental preparations in which systemic toxicity can be avoided.", "contents": "Acetylsalicylic acid hydrolase of gastric mucosa. Acetylsalicylic acid hydrolase activity of rabbit fundic gastric mucosa has been isolated from the soluble 100,000 X g supernate. The enzymatic activity was partially purified by ammonium sulfate precipitation. The Km for acetylsalicylate was 2 mM and pH optimum was 8.6. The activity was insensitive to ionic strength, slightly inhibited by inclusion of 100 mM Cl-, and demonstrated no requirement for Ca2+ or Mg2+. Acetylsalicylic acid esterase was markedly inhibited by sodium cholate and sodium dodecyl sulfate. The enzyme was insensitive to sulfhydryl reagents with the exception of p-chloromercuribenzenesulfonic acid, which markedly inhibited the enzyme. Diisopropyl fluorophosphate (DFP) inhibited enzymatic activity with a Ki of 9 X 10(-9)M. Eserine was also inhibitory with a Ki of 0.25 mM. Inhibition by DFP at low concentration and by eserine at millimolar concentrations suggests that this enzyme is related to the group of aliphatic esterases. Identification of potent inhibitors will enable studies to define the role of this enzyme with the use of experimental preparations in which systemic toxicity can be avoided."}
{"id": "PMID:27101", "title": "Alterations of glucose metabolism during perfusion of rat lung with paraquat.", "content": "Isolated perfused rat lungs were used to investigate effects of paraquat on lung glucose metabolism. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate buffer, pH 7.4, containing albumin and 5.5 mM radiolabeled D-glucose. Control lung glucose utilization, estimated from rate of 3H2O production from [5-3H]glucose, was 44 mumol/h-g dry wt. Pentose cycle activity, based on 14CO2 specific yields at the end of perfusions with [1-14C]- and [6-14C]glucose, was 14% of glucose utilization. During perfusion with 1.5 mM paraquat, glucose utilization increased 28%, 14CO2 production via the pentose cycle increased 182% (P less than 0.005), CO2 production via mitochondrial metabolism increased 39% (P less than 0.02), and the rate of lactate production increased 28% (P less than 0.05). Pyruvate production and the lactate-to-pyruvate ratio were not significantly altered. The data indicate that interaction of paraquat with the lung results in increased turnover of cytoplasmic NADPH and increased mitochondrial metabolism, but no significant change in cytoplasmic redox state. The findings are compatible with intracellular enzymatic reduction of paraquat by an NADPH-requiring reductase.", "contents": "Alterations of glucose metabolism during perfusion of rat lung with paraquat. Isolated perfused rat lungs were used to investigate effects of paraquat on lung glucose metabolism. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate buffer, pH 7.4, containing albumin and 5.5 mM radiolabeled D-glucose. Control lung glucose utilization, estimated from rate of 3H2O production from [5-3H]glucose, was 44 mumol/h-g dry wt. Pentose cycle activity, based on 14CO2 specific yields at the end of perfusions with [1-14C]- and [6-14C]glucose, was 14% of glucose utilization. During perfusion with 1.5 mM paraquat, glucose utilization increased 28%, 14CO2 production via the pentose cycle increased 182% (P less than 0.005), CO2 production via mitochondrial metabolism increased 39% (P less than 0.02), and the rate of lactate production increased 28% (P less than 0.05). Pyruvate production and the lactate-to-pyruvate ratio were not significantly altered. The data indicate that interaction of paraquat with the lung results in increased turnover of cytoplasmic NADPH and increased mitochondrial metabolism, but no significant change in cytoplasmic redox state. The findings are compatible with intracellular enzymatic reduction of paraquat by an NADPH-requiring reductase."}
{"id": "PMID:27104", "title": "Human platelet MAO in drug-free and medicated schizophrenic patients.", "content": "The authors compared platelet monoamine oxidase activity in drug-free chronic and acute schizophrenic patients, medicated chronic schizophrenic patients, and normal controls. A significant decrement in MAO activity was found only in medicated chronic schizophrenic patients. The possible mechanism for this finding is discussed.", "contents": "Human platelet MAO in drug-free and medicated schizophrenic patients. The authors compared platelet monoamine oxidase activity in drug-free chronic and acute schizophrenic patients, medicated chronic schizophrenic patients, and normal controls. A significant decrement in MAO activity was found only in medicated chronic schizophrenic patients. The possible mechanism for this finding is discussed."}
{"id": "PMID:27107", "title": "[The importance of age dependent changes of the organism for therapy (author's transl)].", "content": "Molecular and supramolecular mechanisms of ageing involve biochemical, physiological and morphological alterations of organs. Furthermore physiological disturbances are superimposed by pathological mechanisms of ageing. As a result the number of diseases in higher age increases as well as there are a lot of therapeutical problems. The following paper tries to reveal that physiological and pathological changes of different organs (heart, kidney, lung, brain) influence the therapy of older man. The results demonstrate that it is necessary to stimulate the research of pharmacodynamics and kinetics in the higher age.", "contents": "[The importance of age dependent changes of the organism for therapy (author's transl)]. Molecular and supramolecular mechanisms of ageing involve biochemical, physiological and morphological alterations of organs. Furthermore physiological disturbances are superimposed by pathological mechanisms of ageing. As a result the number of diseases in higher age increases as well as there are a lot of therapeutical problems. The following paper tries to reveal that physiological and pathological changes of different organs (heart, kidney, lung, brain) influence the therapy of older man. The results demonstrate that it is necessary to stimulate the research of pharmacodynamics and kinetics in the higher age."}
{"id": "PMID:27108", "title": "[Contribution to wet and dry weights of mesenchymal and parenchymatous organs of humans and rats during the course of life (author's transl)].", "content": "The wet and dry weights of parenchymatous (lung, heart, liver, kidney) and of mesenchymal organs (aorta, skin, xiphoid cartilage) of humans and rats (both sexes) were investigated during the course of life. Furthermore, these investigations were done on the following rat organs: brain (divided in cerebrum as well as in cerebellum plus pons), spleen, rib cartilage, testis and ovar. The water content of these tissues and organs of both species was calculated by means of their wet and dry weights. The dry weights of the investigated parenchymal and mesenchymal organs of both species remain constant during the whole course of life (pastly until the high senile age)--using freeze-drying. The same is true for the water content: constancy without significant decrease during the investigated life periods and without sex dependent differences.", "contents": "[Contribution to wet and dry weights of mesenchymal and parenchymatous organs of humans and rats during the course of life (author's transl)]. The wet and dry weights of parenchymatous (lung, heart, liver, kidney) and of mesenchymal organs (aorta, skin, xiphoid cartilage) of humans and rats (both sexes) were investigated during the course of life. Furthermore, these investigations were done on the following rat organs: brain (divided in cerebrum as well as in cerebellum plus pons), spleen, rib cartilage, testis and ovar. The water content of these tissues and organs of both species was calculated by means of their wet and dry weights. The dry weights of the investigated parenchymal and mesenchymal organs of both species remain constant during the whole course of life (pastly until the high senile age)--using freeze-drying. The same is true for the water content: constancy without significant decrease during the investigated life periods and without sex dependent differences."}
{"id": "PMID:27109", "title": "[Correlations between age, risk factors for arteriosclerosis and endocrine functions (author's transl)].", "content": "In 377 males and 528 female factory workers basal serum levels of glucose, neutralfat, cholesterol, Na, K, Ca and LH, FSH, TSH, Prolactin, GH, Insulin, total corticoids and testosteron were determined. Mean values and standard deviations as well as correlations between mean basal hormone levels and other serum parameters, blood pressure and relative body weight (Broca Index) and partial correlations excluding age and relative body weight were calculated. Basal serum levels of LH, FSH, GH and prolactin show age and sex dependent secretion patterns. In men serum insulin-, GH- and total corticoid levels correlate positive significant with glucose and cholesterol levels, relative body weight and blood pressure, which possibly shows, that these hormones may play a role in the development of degenerative heart and blood vessel diseases. Testosteron levels and parameters of fat metabolism, relative body weight and diastolic blood pressure correlate negative significant. Obviously testosteron has a protective effect against arterioslcerotic lesions. In women insulin and GH do not have the same importance as in men. Prolactin serum and cholesterol level correlate negative significant. In postmenopausal women LH and FSH serum levels correlate positive significant with glucose and cholesterol levels, blood pressure and relative body weight, the so called risk factors for arteriosclerosis.", "contents": "[Correlations between age, risk factors for arteriosclerosis and endocrine functions (author's transl)]. In 377 males and 528 female factory workers basal serum levels of glucose, neutralfat, cholesterol, Na, K, Ca and LH, FSH, TSH, Prolactin, GH, Insulin, total corticoids and testosteron were determined. Mean values and standard deviations as well as correlations between mean basal hormone levels and other serum parameters, blood pressure and relative body weight (Broca Index) and partial correlations excluding age and relative body weight were calculated. Basal serum levels of LH, FSH, GH and prolactin show age and sex dependent secretion patterns. In men serum insulin-, GH- and total corticoid levels correlate positive significant with glucose and cholesterol levels, relative body weight and blood pressure, which possibly shows, that these hormones may play a role in the development of degenerative heart and blood vessel diseases. Testosteron levels and parameters of fat metabolism, relative body weight and diastolic blood pressure correlate negative significant. Obviously testosteron has a protective effect against arterioslcerotic lesions. In women insulin and GH do not have the same importance as in men. Prolactin serum and cholesterol level correlate negative significant. In postmenopausal women LH and FSH serum levels correlate positive significant with glucose and cholesterol levels, blood pressure and relative body weight, the so called risk factors for arteriosclerosis."}
{"id": "PMID:27110", "title": "[Linguistics of ageing, linguistic Gerontology--Why? (author's transl)].", "content": "Intercourse between the young and the old is accompanied by difficulties in finding the right word. Authentic observations will be presented. These every-day experiences have prompted the search for the felicity conditions of verbal interaction between members of different age groups. This concern is called linguistics of ageing (or, etatolinguistics). It is called linguistic gerontology (or, gerontolinguistics) if older people are involved in the verbal interactions to be investigated. Papers from the fields of intelligence psychology, language psychology, and language sociology have indeed reported differences in verbal scores between groups of different ages. What has not been answered as yet, however, is the question whether these differences are, or may be, responsible for the difficulties arising in verbal interaction between different age groups. A review of hypotheses as to why verbal scores differ between different age groups in the way they do will reveal that this problem has not as yet been solved either. In conclusion, a programme for further research will be outlined.", "contents": "[Linguistics of ageing, linguistic Gerontology--Why? (author's transl)]. Intercourse between the young and the old is accompanied by difficulties in finding the right word. Authentic observations will be presented. These every-day experiences have prompted the search for the felicity conditions of verbal interaction between members of different age groups. This concern is called linguistics of ageing (or, etatolinguistics). It is called linguistic gerontology (or, gerontolinguistics) if older people are involved in the verbal interactions to be investigated. Papers from the fields of intelligence psychology, language psychology, and language sociology have indeed reported differences in verbal scores between groups of different ages. What has not been answered as yet, however, is the question whether these differences are, or may be, responsible for the difficulties arising in verbal interaction between different age groups. A review of hypotheses as to why verbal scores differ between different age groups in the way they do will reveal that this problem has not as yet been solved either. In conclusion, a programme for further research will be outlined."}
{"id": "PMID:27111", "title": "[On the social situation of sick old women (author's transl)].", "content": "By explaining the social situation of the patients in a Berlin hospital for chronic and geriatric diseases, it is demonstrated that financial security and social status of old woman patients are much worse than those of old men. Examples are mentioned to demonstrate which were--and still are--the main causes--that in their earlier years women were paid less for their work and were discriminated because of their sex. If for the future the situation of old women is to be improved, the emancipation of women must advance today.", "contents": "[On the social situation of sick old women (author's transl)]. By explaining the social situation of the patients in a Berlin hospital for chronic and geriatric diseases, it is demonstrated that financial security and social status of old woman patients are much worse than those of old men. Examples are mentioned to demonstrate which were--and still are--the main causes--that in their earlier years women were paid less for their work and were discriminated because of their sex. If for the future the situation of old women is to be improved, the emancipation of women must advance today."}
{"id": "PMID:27112", "title": "[Analyses of space available in homes and day centers for the aged, as well as nursing homes for elderly people, in the FRG. Booking and occupation rate in homes and nursing homes for the aged (author's transl)].", "content": "Further intention of the survey having been conducted to show the consequences of the \"Heimmindestverordnung\" (draft dated Nov. 1974) was to obtain a review of the density of occupancy related to housing for the elderly. In homes for the old the rate of one-bed-rooms significantly increased during the last 15 years, whereas the respective quota for rooms with two, three, or more beds showed a decreasing tendency. In nursing homes density also decreased: the rate of one- and two-bed-rooms increased and the respective frequency of rooms equipped with four and more beds decreased from 55% to 13%. Regarding the density of occupancy also the other data collected such as related to variables as association the investigation-unit belongs to, commencement of operation, federal state, size of community led to some striking findings.", "contents": "[Analyses of space available in homes and day centers for the aged, as well as nursing homes for elderly people, in the FRG. Booking and occupation rate in homes and nursing homes for the aged (author's transl)]. Further intention of the survey having been conducted to show the consequences of the \"Heimmindestverordnung\" (draft dated Nov. 1974) was to obtain a review of the density of occupancy related to housing for the elderly. In homes for the old the rate of one-bed-rooms significantly increased during the last 15 years, whereas the respective quota for rooms with two, three, or more beds showed a decreasing tendency. In nursing homes density also decreased: the rate of one- and two-bed-rooms increased and the respective frequency of rooms equipped with four and more beds decreased from 55% to 13%. Regarding the density of occupancy also the other data collected such as related to variables as association the investigation-unit belongs to, commencement of operation, federal state, size of community led to some striking findings."}
{"id": "PMID:27113", "title": "[Consumer information activities in old age (author's transl)].", "content": "The following feature occupies with consumer information activities in old age. These informations are partial results of a study that was carried out in the Institut f\u00fcr Sozialforschung und Gesellschaftspolitik in Cologne by order of the Arbeitsgemeinschaft der Verbraucher and which deals with chances of consumer policy for people in old age (Naegele 1977). The paper's major elements are, first, essential sources of information of old people (source of supply itself, communication with relatives and friends before buying, written informations), and second, favourite sources of consumer informations to protect and to acquaint old consumers.", "contents": "[Consumer information activities in old age (author's transl)]. The following feature occupies with consumer information activities in old age. These informations are partial results of a study that was carried out in the Institut f\u00fcr Sozialforschung und Gesellschaftspolitik in Cologne by order of the Arbeitsgemeinschaft der Verbraucher and which deals with chances of consumer policy for people in old age (Naegele 1977). The paper's major elements are, first, essential sources of information of old people (source of supply itself, communication with relatives and friends before buying, written informations), and second, favourite sources of consumer informations to protect and to acquaint old consumers."}
{"id": "PMID:27114", "title": "[Working conditions and job-requirement of older industrial blue collar workers and the consequences in employment problems (author's transl)].", "content": "In the following passage the reduced vocational capacity of older workers will be discussed as a consequence of the intended high-capacity of workers as well as the non--human working--conditions in industry. The reduced personal sanity and working capacity of older workers point out the high rate of handicaps and the incapacity of vocational engagement. Problems of employment--and this could be pointed out by the high rates of unemployment amongst older workers--does not signify prejudice but indicates the low profitableness of older workers in the capitalistic production system. Finally discussed will be the contribution of a monetary--conpensatoric against a more prophylactic social policy for a better solution of the vocational problems of older blue-collar workers.", "contents": "[Working conditions and job-requirement of older industrial blue collar workers and the consequences in employment problems (author's transl)]. In the following passage the reduced vocational capacity of older workers will be discussed as a consequence of the intended high-capacity of workers as well as the non--human working--conditions in industry. The reduced personal sanity and working capacity of older workers point out the high rate of handicaps and the incapacity of vocational engagement. Problems of employment--and this could be pointed out by the high rates of unemployment amongst older workers--does not signify prejudice but indicates the low profitableness of older workers in the capitalistic production system. Finally discussed will be the contribution of a monetary--conpensatoric against a more prophylactic social policy for a better solution of the vocational problems of older blue-collar workers."}
{"id": "PMID:27115", "title": "[The effects of the social security system on the life situation of old people (author's transl)].", "content": "The situation of old people is determined by the system of Social Security in a various way. A point of most importance are effects of pensions etc. on the distribution of income. It is shown, that distribution of old-age pensions follows the same scheme, which is dominating in the distribution of primary income. This is due to the basic principles of the Social Security System, which intensify inequality.", "contents": "[The effects of the social security system on the life situation of old people (author's transl)]. The situation of old people is determined by the system of Social Security in a various way. A point of most importance are effects of pensions etc. on the distribution of income. It is shown, that distribution of old-age pensions follows the same scheme, which is dominating in the distribution of primary income. This is due to the basic principles of the Social Security System, which intensify inequality."}
{"id": "PMID:27116", "title": "[Maintenance payments to the elderly (author's transl)].", "content": "The question of the extent older people sustain their livelihood through financial contribution from their children is important sociopolitically inasmuch as claims for payments under the Federal Social Welfare Scheme (Bundessozialhilfegesetz) can only be made where no such private financial support can be given by those next of kin responsible in law. It has been established that in approximately every 14th household in the Federal Republic such maintenance payments are made to at least one member of the older generation (either parents and/or parents-in-law). Seen together with the findings of other inquiries it appears justifiable to assume that these payments are more often remunerations recompensed either materially or otherwise by the older generation rather than a genuine alternative to (necessary) public welfare support. It must therefore be assumed that onesided private financial support carries the odium of \"private relief\" for the recipients, in which case it would run contrary to the intentions of social legislation.", "contents": "[Maintenance payments to the elderly (author's transl)]. The question of the extent older people sustain their livelihood through financial contribution from their children is important sociopolitically inasmuch as claims for payments under the Federal Social Welfare Scheme (Bundessozialhilfegesetz) can only be made where no such private financial support can be given by those next of kin responsible in law. It has been established that in approximately every 14th household in the Federal Republic such maintenance payments are made to at least one member of the older generation (either parents and/or parents-in-law). Seen together with the findings of other inquiries it appears justifiable to assume that these payments are more often remunerations recompensed either materially or otherwise by the older generation rather than a genuine alternative to (necessary) public welfare support. It must therefore be assumed that onesided private financial support carries the odium of \"private relief\" for the recipients, in which case it would run contrary to the intentions of social legislation."}
{"id": "PMID:27117", "title": "[Measuring nursing needs of older people related to actual nursing time in institutions for the aged (author's transl)].", "content": "A great many of the elderly people are in need of care. In offering services accordingly it is necessary to acquire relevant data. The following article gives results of a study which determined 1) the real amount of given nursing care and 2) the measured amount of nursing needs of these patients. The research was done at 10 nursing stations with 210 persons. The results make clear 1) that need of care must be seen in a multidemensional perspective and 2) that much of the psychological and social needs of the patients are not yet satisfied.", "contents": "[Measuring nursing needs of older people related to actual nursing time in institutions for the aged (author's transl)]. A great many of the elderly people are in need of care. In offering services accordingly it is necessary to acquire relevant data. The following article gives results of a study which determined 1) the real amount of given nursing care and 2) the measured amount of nursing needs of these patients. The research was done at 10 nursing stations with 210 persons. The results make clear 1) that need of care must be seen in a multidemensional perspective and 2) that much of the psychological and social needs of the patients are not yet satisfied."}
{"id": "PMID:27118", "title": "[Environment and selfsufficiency of elder man (author's transl)].", "content": "The problems of environment of elderly people are concentrated in social area and in the intimate living space, which can not be maintained sufficiently because of increasing age and decreasing performance. The consequences of mobility in industrial revolution scattered families and also deprived old men of their helpers. Inadequate living rooms and absence of technical comfort especially in the houses of the very aged men produce intense dependence of the own individual performance. Medical data of the spontaneous elected performance informe about the amount of the requirements of daily working capacity. They show low requirements of stress. Spontaneous working load was below of the level of medical well tolerated effort. In healthy men no signs of overloading have been registrated. Seldom removal in old age pensions before the age of eighty is indicated by illness but frequently social motivation predominates. On the contrary considerable insufficiency in social and medical providing exist after acut illness, what is to improve by special hospitals for rehabilitation of older people and by a grid of social stations. By this method it might be possible to save a great amount of money by governments that now has to be payed for exorbitant expansive assistance which is medical not indicated.", "contents": "[Environment and selfsufficiency of elder man (author's transl)]. The problems of environment of elderly people are concentrated in social area and in the intimate living space, which can not be maintained sufficiently because of increasing age and decreasing performance. The consequences of mobility in industrial revolution scattered families and also deprived old men of their helpers. Inadequate living rooms and absence of technical comfort especially in the houses of the very aged men produce intense dependence of the own individual performance. Medical data of the spontaneous elected performance informe about the amount of the requirements of daily working capacity. They show low requirements of stress. Spontaneous working load was below of the level of medical well tolerated effort. In healthy men no signs of overloading have been registrated. Seldom removal in old age pensions before the age of eighty is indicated by illness but frequently social motivation predominates. On the contrary considerable insufficiency in social and medical providing exist after acut illness, what is to improve by special hospitals for rehabilitation of older people and by a grid of social stations. By this method it might be possible to save a great amount of money by governments that now has to be payed for exorbitant expansive assistance which is medical not indicated."}
{"id": "PMID:27119", "title": "[On postoperative azotemia in geriatric surgery: significance, risk groups, possibilities of prophylaxis (author's transl)].", "content": "1032 Interventions on geriatric patients beeing more than 70 years old between 1966 and 1975 demonstrate the significance of azotemia in the postoperativ stage of the disease appears as well as its dependence upon prehospital factors, type and localisation also on the extension and duration on the intervention in each single case. Since it is hardly possible to exert an influence on the preliminary stress due to the old age and on the dysfunction determined by involution of the parenchymatose organs important for the course of the postoperative stage, a particular emphasis should be laid upon the prophylactic aspekt to the purpose of an appropriate screening against vegetativ-visceral, renally effective shock reflexes (hepatorenal syndrome) and on the other, usually extra-renal factors (PH 203R, splanchnic block). Further possibilities: considerate elimination of pain and general anesthesia, purpuseful and quick operative technique, improvement of the apparatus and instruments, after-treatment specific for the given case so as one consisting of a prophylaxis against pneumonia through a rapid reactivation of the operated person. However, regardless to all the professional advance made in this field, the primary human approach to the aged patient and to his life expectancy should be made due allowance for.", "contents": "[On postoperative azotemia in geriatric surgery: significance, risk groups, possibilities of prophylaxis (author's transl)]. 1032 Interventions on geriatric patients beeing more than 70 years old between 1966 and 1975 demonstrate the significance of azotemia in the postoperativ stage of the disease appears as well as its dependence upon prehospital factors, type and localisation also on the extension and duration on the intervention in each single case. Since it is hardly possible to exert an influence on the preliminary stress due to the old age and on the dysfunction determined by involution of the parenchymatose organs important for the course of the postoperative stage, a particular emphasis should be laid upon the prophylactic aspekt to the purpose of an appropriate screening against vegetativ-visceral, renally effective shock reflexes (hepatorenal syndrome) and on the other, usually extra-renal factors (PH 203R, splanchnic block). Further possibilities: considerate elimination of pain and general anesthesia, purpuseful and quick operative technique, improvement of the apparatus and instruments, after-treatment specific for the given case so as one consisting of a prophylaxis against pneumonia through a rapid reactivation of the operated person. However, regardless to all the professional advance made in this field, the primary human approach to the aged patient and to his life expectancy should be made due allowance for."}
{"id": "PMID:27120", "title": "Ketamine sequelae. Evaluation of the ability of various premedicants to attenuate its psychic actions.", "content": "The ability of a number of drugs to abolish the emergence delirium and unpleasant dreams which follow anaesthesia induced with 2 mg/kg ketamine was studied. These included three benzodiazepines, droperidol and 'neurolept' combinations and four commonly-used premedicants. When given intravenously 10 min before induction of anaesthesia flunitrazepam and lorazepam gave best results. In a subsequent study, these two benzodiazepines and diazepam were given intravenously 30-40 min before induction of anaesthesia. There was no doubt that 4 mg lorazepam gave the greatest protection and is worthy of further study in this respect.", "contents": "Ketamine sequelae. Evaluation of the ability of various premedicants to attenuate its psychic actions. The ability of a number of drugs to abolish the emergence delirium and unpleasant dreams which follow anaesthesia induced with 2 mg/kg ketamine was studied. These included three benzodiazepines, droperidol and 'neurolept' combinations and four commonly-used premedicants. When given intravenously 10 min before induction of anaesthesia flunitrazepam and lorazepam gave best results. In a subsequent study, these two benzodiazepines and diazepam were given intravenously 30-40 min before induction of anaesthesia. There was no doubt that 4 mg lorazepam gave the greatest protection and is worthy of further study in this respect."}
{"id": "PMID:27121", "title": "Ketamine-iorazepam. Attenuation of psychic sequelae of ketamine by lorazepam.", "content": "The intravenous, intramuscular and oral administration of 4 mg lorazepam given to adults will effectively reduce the psychic sequelae of ketamine to acceptable limits.", "contents": "Ketamine-iorazepam. Attenuation of psychic sequelae of ketamine by lorazepam. The intravenous, intramuscular and oral administration of 4 mg lorazepam given to adults will effectively reduce the psychic sequelae of ketamine to acceptable limits."}
{"id": "PMID:27123", "title": "[The solutibility of local anaesthetics in cerebrospinal fluid and the dependency of the process on the hydrogene ion concentration (author's transl)].", "content": "Reports on in vitro precipitation of local anesthetics suggested the possibility of a damaging effect on nervous tissue with spinal anesthesia. The present assays showed that the solubility of local anesthetics in aqueous media decreases with rising pH-levels. The partial pressure of CO2 determines the pH-level of the cerebrospinal fluid, the level ranging at about 7.35 + 0.011 (95% range: 7.327-7.371). The solubilities calculated for a pH of 7.371 (at 37 degrees C) are as follows: Bupivacaine.HCl 0.83+/-0.10 mh/ml Carticaine.HCl 27 +/-2.8 mg/ml Lidocaine.HCl 24 +/-1.3 mg/ml Mepivacaine.HCl 14.8 +/- 0.2 mg/ml Tetracaine.HCl 1.4 +/- 0.12 mg/ml.", "contents": "[The solutibility of local anaesthetics in cerebrospinal fluid and the dependency of the process on the hydrogene ion concentration (author's transl)]. Reports on in vitro precipitation of local anesthetics suggested the possibility of a damaging effect on nervous tissue with spinal anesthesia. The present assays showed that the solubility of local anesthetics in aqueous media decreases with rising pH-levels. The partial pressure of CO2 determines the pH-level of the cerebrospinal fluid, the level ranging at about 7.35 + 0.011 (95% range: 7.327-7.371). The solubilities calculated for a pH of 7.371 (at 37 degrees C) are as follows: Bupivacaine.HCl 0.83+/-0.10 mh/ml Carticaine.HCl 27 +/-2.8 mg/ml Lidocaine.HCl 24 +/-1.3 mg/ml Mepivacaine.HCl 14.8 +/- 0.2 mg/ml Tetracaine.HCl 1.4 +/- 0.12 mg/ml."}
{"id": "PMID:27124", "title": "[pH of the cerebro spinal fluid during subdural block (author's transl)].", "content": "This study was initiated by other authors who found that bupivacaine precipitated together with spinal fluid in vitro and who assumed that during spinal anaesthesia complications might be possible. Under the influence of several local anaesthetic agents the pH of the spinal fluid and in 160 cases the precipitation was examined. There was no precipitation. The experimental conditions were nearly in vivo conditions. The results differed clearly from those in vitro. While in vitro bupivacaine precipitated from a pH higher than 7.37 in concentrations higher than 0.8 mg/ml [2], the pH of the spinal fluid in vivo was lower than 7.35 continually and the concentration of bupivacaine not higher than 0.3 mg/ml. This means that the border of bupivacaine precipitation is by far not reached in vivo and that complications therefore are not possible.", "contents": "[pH of the cerebro spinal fluid during subdural block (author's transl)]. This study was initiated by other authors who found that bupivacaine precipitated together with spinal fluid in vitro and who assumed that during spinal anaesthesia complications might be possible. Under the influence of several local anaesthetic agents the pH of the spinal fluid and in 160 cases the precipitation was examined. There was no precipitation. The experimental conditions were nearly in vivo conditions. The results differed clearly from those in vitro. While in vitro bupivacaine precipitated from a pH higher than 7.37 in concentrations higher than 0.8 mg/ml [2], the pH of the spinal fluid in vivo was lower than 7.35 continually and the concentration of bupivacaine not higher than 0.3 mg/ml. This means that the border of bupivacaine precipitation is by far not reached in vivo and that complications therefore are not possible."}
{"id": "PMID:27127", "title": "[Changes of circulation, blood gases, acid-base-and metabolism during neurolept-analgesia with and without beta-receptor blockers in electro coagulation of Gasser's ganglion (author's transl)].", "content": "The cardiovascular, blood gas, acid-base and metabolic changes occurring during operative stress were studied in 10 elderly, metabolically healthy patients, suffering from idiopathic trigeminal neuralgia, who underwent electrocoagulation of the gasserian ganglion under neuroleptanalgesia. In a group of 12 patients undergoing the same operative procedure and anesthesthetic management, we investigated the effects of administration of a beta blocking agent on these parameters. Intraoperative rises of blood pressure and tachycardia were prevented by intravenous administration of 0.4 mg Pindolol (Visken), whereas increases in the blood glucose levels at the end of the operation were the same. The increase of glycerol, free fatty acids and ketone bodies was markedly reduced after pretreatment with the beta blocker compared with the controlgroup. In the patients without beta blocker treatment pH and standard bicarbonate at the end of the operation were lower as the result of the stimulation of ketogenesis.", "contents": "[Changes of circulation, blood gases, acid-base-and metabolism during neurolept-analgesia with and without beta-receptor blockers in electro coagulation of Gasser's ganglion (author's transl)]. The cardiovascular, blood gas, acid-base and metabolic changes occurring during operative stress were studied in 10 elderly, metabolically healthy patients, suffering from idiopathic trigeminal neuralgia, who underwent electrocoagulation of the gasserian ganglion under neuroleptanalgesia. In a group of 12 patients undergoing the same operative procedure and anesthesthetic management, we investigated the effects of administration of a beta blocking agent on these parameters. Intraoperative rises of blood pressure and tachycardia were prevented by intravenous administration of 0.4 mg Pindolol (Visken), whereas increases in the blood glucose levels at the end of the operation were the same. The increase of glycerol, free fatty acids and ketone bodies was markedly reduced after pretreatment with the beta blocker compared with the controlgroup. In the patients without beta blocker treatment pH and standard bicarbonate at the end of the operation were lower as the result of the stimulation of ketogenesis."}
{"id": "PMID:27129", "title": "Acid aspiration during laparoscopy.", "content": "The prophylactic efficacy of pre-operative antacid administration was shown by comparing the pH and volumes of gastric contents in 50 female patients treated with 10 ml of Mist. Magnesium Trisilicate B.P.C. with that of 50 controls. Routine antacid prophylaxis was advocated for all patients undergoing pelvic laparoscopy as intra-operative conditions increase the risk of pulmonary acid aspiration.", "contents": "Acid aspiration during laparoscopy. The prophylactic efficacy of pre-operative antacid administration was shown by comparing the pH and volumes of gastric contents in 50 female patients treated with 10 ml of Mist. Magnesium Trisilicate B.P.C. with that of 50 controls. Routine antacid prophylaxis was advocated for all patients undergoing pelvic laparoscopy as intra-operative conditions increase the risk of pulmonary acid aspiration."}
{"id": "PMID:27131", "title": "Placental transfer of lidocaine: effects of fetal acidosis.", "content": "To investigate whether fetal acidosis increases the placental transfer of lidocaine, resulting in higher fetal blood levels of the drug, lidocaine was infused intravenously into ten pregnant ewes to maintain plasma levels of 2-4 microgram/ml. After maternal-fetal equilibrium was reached, the fetus was made acidotic by infusing lactic acid intravenously. Fetal blood pH decreased from 7.35 to 7.10. With fetal acidemia, fetal blood lidocaine levels increased significantly from 1.60 +/- 0.11 microgram/ml to 2.72 +/- 0.26 microgram/ml. The fetal-maternal lidocaine ratio increased from 0.76 to 1.21. Correction of the acidosis by bicarbonate infusion returned the fetal-maternal ratios to control values. It is concluded that acidosis in the fetus may result in trapping of ionized lidocaine in the fetal circulation and increase the transfer of lidocaine across the placenta.", "contents": "Placental transfer of lidocaine: effects of fetal acidosis. To investigate whether fetal acidosis increases the placental transfer of lidocaine, resulting in higher fetal blood levels of the drug, lidocaine was infused intravenously into ten pregnant ewes to maintain plasma levels of 2-4 microgram/ml. After maternal-fetal equilibrium was reached, the fetus was made acidotic by infusing lactic acid intravenously. Fetal blood pH decreased from 7.35 to 7.10. With fetal acidemia, fetal blood lidocaine levels increased significantly from 1.60 +/- 0.11 microgram/ml to 2.72 +/- 0.26 microgram/ml. The fetal-maternal lidocaine ratio increased from 0.76 to 1.21. Correction of the acidosis by bicarbonate infusion returned the fetal-maternal ratios to control values. It is concluded that acidosis in the fetus may result in trapping of ionized lidocaine in the fetal circulation and increase the transfer of lidocaine across the placenta."}
{"id": "PMID:27132", "title": "Hemoglobin Creteil: oxygen transport by erythrocytes. In-vitro and in-vivo studies in a high oxygen-affinity mutant hemoglobin.", "content": "Hemoglobin Hb) Creteil alpha2beta(2)89 (F5) Ser leads to Asn is a high oxygen-affinity variant that has a low cooperativity, a decreased Bohr effect, and does not interact with diphosphoglycerate (DPG) (1). This hemoglobin variant was silent by routine electrophoresis. Careful analyses of the oxygen dissociation curves of erythrocytes, determined at varying pH and Pco2 in fresh and DPG-depleted cells, gave extensive information on the abnormal function of the mutant hemoglobin. From the O2 dissociation curves of the erythrocytes of the heterozygous subject it appeared that Hb Creteil is inappropriate for O2 transport to the tissues because it remained completely saturated with O2 at normal physiologic levels of Po2. In-vivo measurements showed that only one half of the total hemoglobin present actually participated in oxygen transport. Polycythemia should therefore be maintained within clinically tolerable limits because it helps to keep arterial Po2 and Pvo2 close to their normal values and thus protects the individual from a permanent increase in blood flow.", "contents": "Hemoglobin Creteil: oxygen transport by erythrocytes. In-vitro and in-vivo studies in a high oxygen-affinity mutant hemoglobin. Hemoglobin Hb) Creteil alpha2beta(2)89 (F5) Ser leads to Asn is a high oxygen-affinity variant that has a low cooperativity, a decreased Bohr effect, and does not interact with diphosphoglycerate (DPG) (1). This hemoglobin variant was silent by routine electrophoresis. Careful analyses of the oxygen dissociation curves of erythrocytes, determined at varying pH and Pco2 in fresh and DPG-depleted cells, gave extensive information on the abnormal function of the mutant hemoglobin. From the O2 dissociation curves of the erythrocytes of the heterozygous subject it appeared that Hb Creteil is inappropriate for O2 transport to the tissues because it remained completely saturated with O2 at normal physiologic levels of Po2. In-vivo measurements showed that only one half of the total hemoglobin present actually participated in oxygen transport. Polycythemia should therefore be maintained within clinically tolerable limits because it helps to keep arterial Po2 and Pvo2 close to their normal values and thus protects the individual from a permanent increase in blood flow."}
{"id": "PMID:27134", "title": "Cold injuries in Kashmir, December 1971.", "content": "A total of 847 cases of cold injury occurred within the short space of 2 weeks during the Indo-Pakistan conflict in Kashmir in December 1971. The management of these cases and their end results are described. A combination of drugs consisting of low-molecular-weight dextran, an anti-inflammatory agent, and a vasodilator was tried with encouraging results. A conservative attitude towards ablation of necrosed tissues paid good dividends.", "contents": "Cold injuries in Kashmir, December 1971. A total of 847 cases of cold injury occurred within the short space of 2 weeks during the Indo-Pakistan conflict in Kashmir in December 1971. The management of these cases and their end results are described. A combination of drugs consisting of low-molecular-weight dextran, an anti-inflammatory agent, and a vasodilator was tried with encouraging results. A conservative attitude towards ablation of necrosed tissues paid good dividends."}
{"id": "PMID:27135", "title": "A disorder of biogenic amines in dihydropteridine reductase deficiency.", "content": "A severe deficiency of dihydropteridine reductase (DHPR) in liver, brain, and cultured skin fibroblasts was demonstrated in a child with hyperphenylalaninemia and an atypical form of phenylketonuria. DHPR is required for regeneration of the cofactor, tetrahydrobiopterin. The cofactor is essential in hydroxylation of aromatic amino acid precursors in the biosynthesis of neurotransmitters, serotonin, dopamine, and norepinephrine. In gray tissue at brain biopsy, dopamine was low at 3 ng per gram of tissue, serotonin was barely detected, and norepinephrine appeared high at 1600 ng per gram. In cerebrospinal fluid, homovanillic acid (HVA) was low normal at 33 ng/ml, 5-hydroxyindoleacetic acid (5-HIAA) was low at 4.2 ng/ml, and after a high dose of oral probenecid there was impaired accumulation of HVA to 128 ng/ml and 5-HIAA to 22.4 ng/ml. When the patient was 22 months of age, treatment with hydroxylated aromatic amino acid precursors was initiated, and after three months HVA and 5-HIAA levels were increased in CSF. The apparent restoration of biogenic amines in brain appears to have delayed the rate of neurological deterioration. DHPR activity in cultured skin fibroblasts of children with persistent hyperphenylalaninemia should permit early diagnosis and early treatment of this disorder.", "contents": "A disorder of biogenic amines in dihydropteridine reductase deficiency. A severe deficiency of dihydropteridine reductase (DHPR) in liver, brain, and cultured skin fibroblasts was demonstrated in a child with hyperphenylalaninemia and an atypical form of phenylketonuria. DHPR is required for regeneration of the cofactor, tetrahydrobiopterin. The cofactor is essential in hydroxylation of aromatic amino acid precursors in the biosynthesis of neurotransmitters, serotonin, dopamine, and norepinephrine. In gray tissue at brain biopsy, dopamine was low at 3 ng per gram of tissue, serotonin was barely detected, and norepinephrine appeared high at 1600 ng per gram. In cerebrospinal fluid, homovanillic acid (HVA) was low normal at 33 ng/ml, 5-hydroxyindoleacetic acid (5-HIAA) was low at 4.2 ng/ml, and after a high dose of oral probenecid there was impaired accumulation of HVA to 128 ng/ml and 5-HIAA to 22.4 ng/ml. When the patient was 22 months of age, treatment with hydroxylated aromatic amino acid precursors was initiated, and after three months HVA and 5-HIAA levels were increased in CSF. The apparent restoration of biogenic amines in brain appears to have delayed the rate of neurological deterioration. DHPR activity in cultured skin fibroblasts of children with persistent hyperphenylalaninemia should permit early diagnosis and early treatment of this disorder."}
{"id": "PMID:27137", "title": "Stability of antibiotics and amino acids in two synthetic L-amino acid solutions commonly used for total parenteral nutrition in children.", "content": "The stability and interaction at 29 degrees C of ampicillin, carbenicillin, gentamicin, and polymyxin B were examined in a common electrolyte solution, invertose darrow, and in two synthetic l-amino acid solutions, one commercial (vamin with fructose; Vitrum) and the other a neonatal preparation modified for use in newborn infants. The concentration of amino acids was measured before and after the addition of these antibiotics. The concentration of antibiotics was measured over a 24-h period with a microbiological method. The concentration of ampicillin in invertose darrow fell 52%, and in vamin with fructose it fell 69%, whereas in the neonatal preparation the fall was only 22%. The concentration of carbenicillin in vamin with fructose fell 37%, and in the neonatal preparation it fell 31%. The combination of ampicillin or carbenicillin with gentamicin or polymyxin B did not influence the activity of the penicillins. The concentration of gentamicin and polymyxin B was unchanged in all solutions over a 24-h period. With the exception of cystine, the concentration of all amino acids remained constant after 24 h in the neonatal preparation with and without the different combinations of antibiotics. For cystine there was a fall of 20 to 30%.", "contents": "Stability of antibiotics and amino acids in two synthetic L-amino acid solutions commonly used for total parenteral nutrition in children. The stability and interaction at 29 degrees C of ampicillin, carbenicillin, gentamicin, and polymyxin B were examined in a common electrolyte solution, invertose darrow, and in two synthetic l-amino acid solutions, one commercial (vamin with fructose; Vitrum) and the other a neonatal preparation modified for use in newborn infants. The concentration of amino acids was measured before and after the addition of these antibiotics. The concentration of antibiotics was measured over a 24-h period with a microbiological method. The concentration of ampicillin in invertose darrow fell 52%, and in vamin with fructose it fell 69%, whereas in the neonatal preparation the fall was only 22%. The concentration of carbenicillin in vamin with fructose fell 37%, and in the neonatal preparation it fell 31%. The combination of ampicillin or carbenicillin with gentamicin or polymyxin B did not influence the activity of the penicillins. The concentration of gentamicin and polymyxin B was unchanged in all solutions over a 24-h period. With the exception of cystine, the concentration of all amino acids remained constant after 24 h in the neonatal preparation with and without the different combinations of antibiotics. For cystine there was a fall of 20 to 30%."}
{"id": "PMID:27138", "title": "Chloramphenicol resistance in Streptococcus pneumoniae: enzymatic acetylation and possible plasmid linkage.", "content": "Clinical isolates of Streptococcus pneumoniae resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of S. pneumoniae in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be O-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a \"cured\" clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in S. pneumoniae.", "contents": "Chloramphenicol resistance in Streptococcus pneumoniae: enzymatic acetylation and possible plasmid linkage. Clinical isolates of Streptococcus pneumoniae resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of S. pneumoniae in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be O-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a \"cured\" clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in S. pneumoniae."}
{"id": "PMID:27139", "title": "Irreversible effects of serum proteins on beta-lactam antibiotics.", "content": "The chromogenic cephalosporin nitrocefin (87/312) demonstrates rapid and visible instability to serum from many species. This phenomenon was distinct from serum binding, being significantly slower. Destruction of another cephalosporin, 10485, by serum appeared to account for some anomalous results during investigation into its human pharmacokinetics. Many cephalosporins of very different structures also showed serum instability, unrelated to their degrees of serum binding as measured by plate assay. Extrapolation could not be made from one species to another with regard to either binding or instability. Small changes in the chemical structures of the 3- and 7-substituents of the cephalosporins made profound changes in their susceptibility to serum attack. The decomposition is pH dependent, occurring more slowly at acid pH, and is due to a high-molecular-weight component of serum that resists boiling for several minutes. Isoelectric focusing of serum from several animal species gave various species-specific bands that decomposed nitrocefin. The inactivation of nitrocefin was not entirely parallel with that of 10485 and was inhibited by it. All other beta-lactam compounds tested also inhibited the reaction, much greater concentrations usually being necessary when the inhibitor was stable to serum. The complex that causes breakdown of the beta-lactam compounds is not necessarily the same as the one causing serum binding. It is postulated that serum may affect most other beta-lactam antibiotics in a similar way, although in most cases, this only occurs to a very slight extent.", "contents": "Irreversible effects of serum proteins on beta-lactam antibiotics. The chromogenic cephalosporin nitrocefin (87/312) demonstrates rapid and visible instability to serum from many species. This phenomenon was distinct from serum binding, being significantly slower. Destruction of another cephalosporin, 10485, by serum appeared to account for some anomalous results during investigation into its human pharmacokinetics. Many cephalosporins of very different structures also showed serum instability, unrelated to their degrees of serum binding as measured by plate assay. Extrapolation could not be made from one species to another with regard to either binding or instability. Small changes in the chemical structures of the 3- and 7-substituents of the cephalosporins made profound changes in their susceptibility to serum attack. The decomposition is pH dependent, occurring more slowly at acid pH, and is due to a high-molecular-weight component of serum that resists boiling for several minutes. Isoelectric focusing of serum from several animal species gave various species-specific bands that decomposed nitrocefin. The inactivation of nitrocefin was not entirely parallel with that of 10485 and was inhibited by it. All other beta-lactam compounds tested also inhibited the reaction, much greater concentrations usually being necessary when the inhibitor was stable to serum. The complex that causes breakdown of the beta-lactam compounds is not necessarily the same as the one causing serum binding. It is postulated that serum may affect most other beta-lactam antibiotics in a similar way, although in most cases, this only occurs to a very slight extent."}
{"id": "PMID:27140", "title": "Antimicrobial susceptibility patterns of Streptococcus pneumoniae.", "content": "Fifty clinical isolates of Streptococcus pneumoniae received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests. No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin. This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin. An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance. Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms. Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade. However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy.", "contents": "Antimicrobial susceptibility patterns of Streptococcus pneumoniae. Fifty clinical isolates of Streptococcus pneumoniae received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests. No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin. This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin. An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance. Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms. Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade. However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy."}
{"id": "PMID:27141", "title": "Susceptibility of skin and throat strains of group A streptococci to rosamicin and erythromycin.", "content": "The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 mug of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 mug of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.", "contents": "Susceptibility of skin and throat strains of group A streptococci to rosamicin and erythromycin. The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 mug of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 mug of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin."}
{"id": "PMID:27146", "title": "The action of lecithin monolayers on mosquitoes I. General observations.", "content": "Monolayers of pure egg-lecithin at maximum equilibrium pressure were tested against eight species of mosquito in the laboratory, Anopheline larvae were prevented from surfacing and died in water of low dissolved oxygen content, but culicine larvae survived. The pupae of all species except Culex p. fatigans were killed. Effects on floating eggs, pupal-adult eclosion and adult behaviour are also reported.", "contents": "The action of lecithin monolayers on mosquitoes I. General observations. Monolayers of pure egg-lecithin at maximum equilibrium pressure were tested against eight species of mosquito in the laboratory, Anopheline larvae were prevented from surfacing and died in water of low dissolved oxygen content, but culicine larvae survived. The pupae of all species except Culex p. fatigans were killed. Effects on floating eggs, pupal-adult eclosion and adult behaviour are also reported."}
{"id": "PMID:27147", "title": "The action of lecithin monolayers on mosquitoes. II. Action on the respiratory structures.", "content": "Experiments on the interaction between the water surface and the respiratory structures of larvae and pupae of five species of mosquitoes showed that in the presence of a lecithin monolayer, a stable, soap-bubble type film is formed which prevents the insect from surfacing. Subsequently, wetting of the hydrophobic areas takes place. In pupae, buoyancy is lost through flooding of the ventral air space.", "contents": "The action of lecithin monolayers on mosquitoes. II. Action on the respiratory structures. Experiments on the interaction between the water surface and the respiratory structures of larvae and pupae of five species of mosquitoes showed that in the presence of a lecithin monolayer, a stable, soap-bubble type film is formed which prevents the insect from surfacing. Subsequently, wetting of the hydrophobic areas takes place. In pupae, buoyancy is lost through flooding of the ventral air space."}
{"id": "PMID:27151", "title": "Hypotensive action of beta-blocking drugs injected into the cerebral ventricle of the rat.", "content": "Pindolol, propranolol, practolol, N-isopropyl-p-nitrophenyl-ethanolamine (INPEA), d and l-alprenolol were injected into the lateral cerebral ventricle of the anaesthetized rat. Except for INPEA, which has no action at the doses used, these various beta-blocking agents produce a dose-related fall in blood pressure. D-alprenolol and practolol seem to be the least active of the hypotensive agents. Our results show some relationship between the beta-blocking potency of the drugs studied and the hypotension induced when they were injected in the lateral ventricle.", "contents": "Hypotensive action of beta-blocking drugs injected into the cerebral ventricle of the rat. Pindolol, propranolol, practolol, N-isopropyl-p-nitrophenyl-ethanolamine (INPEA), d and l-alprenolol were injected into the lateral cerebral ventricle of the anaesthetized rat. Except for INPEA, which has no action at the doses used, these various beta-blocking agents produce a dose-related fall in blood pressure. D-alprenolol and practolol seem to be the least active of the hypotensive agents. Our results show some relationship between the beta-blocking potency of the drugs studied and the hypotension induced when they were injected in the lateral ventricle."}
{"id": "PMID:27152", "title": "Ganglion blocking effects of streptomycin.", "content": "The effects of streptomycin on the postganglionic compound action potential, presynaptic nerve terminal spike and preganglionic nerve action potnetial were studied in rabbit and rat superior cervical gnaglia. Streptomycin had a dose-dependent, blocking effect on the postganglionic action potential. The drug was found to have a preferential blocking effect on the first spike, S1, of the compound postganglionic action potential, but the second, S2, major spike was depressed at higher concentrations. At 1 mg/ml, streptomycin reduced the amplitude of the presynaptic nerve terminal action potential, but had no significant effect on the action potential recorded from the cervical sympathetic preganglionic nerve. Increasing the concentrations of Ca++ in the bathing solution antagonized the blocking effect of the antibiotic on the postganglionic action potential. The results are interpreted as indicating that ganglionic blockade by streptomycin is due, mainly, to a presynaptic effect which results in a decreased release of acetylcholine.", "contents": "Ganglion blocking effects of streptomycin. The effects of streptomycin on the postganglionic compound action potential, presynaptic nerve terminal spike and preganglionic nerve action potnetial were studied in rabbit and rat superior cervical gnaglia. Streptomycin had a dose-dependent, blocking effect on the postganglionic action potential. The drug was found to have a preferential blocking effect on the first spike, S1, of the compound postganglionic action potential, but the second, S2, major spike was depressed at higher concentrations. At 1 mg/ml, streptomycin reduced the amplitude of the presynaptic nerve terminal action potential, but had no significant effect on the action potential recorded from the cervical sympathetic preganglionic nerve. Increasing the concentrations of Ca++ in the bathing solution antagonized the blocking effect of the antibiotic on the postganglionic action potential. The results are interpreted as indicating that ganglionic blockade by streptomycin is due, mainly, to a presynaptic effect which results in a decreased release of acetylcholine."}
{"id": "PMID:27153", "title": "An experimental non-invasive animal technique for measuring nasal airway resistance: I. Adrenergic and antihistaminic agents.", "content": "A non-invasive technically simple and sensitive method is described for the determination of nasal airway resistance (NAR). Aerosolized saline elicited a +/- 7% change in baseline NAR, duration 2 minutes, whereas aerosolized histamine increased NAR, duration is greater than 30 minutes. Aerosolized phenylephrine, norepinephrine, and oxymetrazoline elicited dose related decongestive response in a naris subjected to prior congestion (aerosolized histamine). Both H1 and H2 receptors are involved in the congestive response to intranasal histamine.", "contents": "An experimental non-invasive animal technique for measuring nasal airway resistance: I. Adrenergic and antihistaminic agents. A non-invasive technically simple and sensitive method is described for the determination of nasal airway resistance (NAR). Aerosolized saline elicited a +/- 7% change in baseline NAR, duration 2 minutes, whereas aerosolized histamine increased NAR, duration is greater than 30 minutes. Aerosolized phenylephrine, norepinephrine, and oxymetrazoline elicited dose related decongestive response in a naris subjected to prior congestion (aerosolized histamine). Both H1 and H2 receptors are involved in the congestive response to intranasal histamine."}
{"id": "PMID:27149", "title": "[Nonspecific aorto-arteritis. Anatomo-pathological study of 18 cases].", "content": "The present study comprises a pathological review of 18 necropsy cases with nonspecific aorto-arteritis (Takayasu's disease), autopsied at the Instituto Nacional de Cardiolog\u00eda of Mexico up to 1976. There were 11 females and 7 males with an average age at the time of death of 21.5 years. A comparison according to the distribution and extention of arterial lesions disclosed that our cases are often less classical than those described from Japan. The principal arterial changes were stenosis, occlusion, dilatation and aneurysm formation in the aorta, its branches and main pulmonary artery. More often than not the aorta was extensively involved. The aortic arch syndrome and renovascular hypertension were almost equally present in this serie and an unusual high incidence of coronary artery involvement (33%) leading to myocardial infarction (50%) also was observed. The significance of the intrapulmonary vascular changes in Takayasu's arteritis is discussed.", "contents": "[Nonspecific aorto-arteritis. Anatomo-pathological study of 18 cases]. The present study comprises a pathological review of 18 necropsy cases with nonspecific aorto-arteritis (Takayasu's disease), autopsied at the Instituto Nacional de Cardiolog\u00eda of Mexico up to 1976. There were 11 females and 7 males with an average age at the time of death of 21.5 years. A comparison according to the distribution and extention of arterial lesions disclosed that our cases are often less classical than those described from Japan. The principal arterial changes were stenosis, occlusion, dilatation and aneurysm formation in the aorta, its branches and main pulmonary artery. More often than not the aorta was extensively involved. The aortic arch syndrome and renovascular hypertension were almost equally present in this serie and an unusual high incidence of coronary artery involvement (33%) leading to myocardial infarction (50%) also was observed. The significance of the intrapulmonary vascular changes in Takayasu's arteritis is discussed."}
{"id": "PMID:27154", "title": "Age-dependence of renal tubular reabsorption of nitrofurantoin.", "content": "Nitrofurantoin is rapidly excreted in adult rats. However, in 5 to 15 days old rats the renal excretion of nitrofurantoin is diminshed by a high rate of reabsorption. Because nitrofurantoin has a pKa of 7.2 its tubular reabsorption is influenced by the urine pH but is independent of urine flow. About 50% of an administered dose of nitrofurantoin is recovered as metabolites in the urine of both young and adult rats. Probenecid blocks the active tubular secretion of nitrofurantoin independently of age and reduces its rate of renal clearance. Induction of drug metabolizing enzymes by pretreatment with phenobarbital was without effect either on the metabolism or renal excretion of nitrofurantoin nor could the renal excretion of this drug be diminished by repeated administration. The age-dependent difference in the rate of renal excretion of nitrofurantion is due to the high rate of tubular reabsorption in the young animals. This study provides experimental support for the therapeutic use of nitrofurantoin in the neonatal period.", "contents": "Age-dependence of renal tubular reabsorption of nitrofurantoin. Nitrofurantoin is rapidly excreted in adult rats. However, in 5 to 15 days old rats the renal excretion of nitrofurantoin is diminshed by a high rate of reabsorption. Because nitrofurantoin has a pKa of 7.2 its tubular reabsorption is influenced by the urine pH but is independent of urine flow. About 50% of an administered dose of nitrofurantoin is recovered as metabolites in the urine of both young and adult rats. Probenecid blocks the active tubular secretion of nitrofurantoin independently of age and reduces its rate of renal clearance. Induction of drug metabolizing enzymes by pretreatment with phenobarbital was without effect either on the metabolism or renal excretion of nitrofurantoin nor could the renal excretion of this drug be diminished by repeated administration. The age-dependent difference in the rate of renal excretion of nitrofurantion is due to the high rate of tubular reabsorption in the young animals. This study provides experimental support for the therapeutic use of nitrofurantoin in the neonatal period."}
{"id": "PMID:27155", "title": "Hypersensitivity to salicylazosulfapyridine: renal and hepatic toxic reactions.", "content": "Salicylazosulfapyridine has been used for a number of years as therapy for ulcerative colitis. Reported toxicities are usually minor. This case report represents an acute allergic reaction to the drug. Characterized by fever, rash, eosinophilia, nephritis, and hepatitis. Resolution occurred with discontinuation of salicylazosulfapyridine. Although similar reactions have been reported with the antimicrobial sulfonamides, none has been fully described with salicylazosulfapyridine, a combination of a sulfonamide and salicylate.", "contents": "Hypersensitivity to salicylazosulfapyridine: renal and hepatic toxic reactions. Salicylazosulfapyridine has been used for a number of years as therapy for ulcerative colitis. Reported toxicities are usually minor. This case report represents an acute allergic reaction to the drug. Characterized by fever, rash, eosinophilia, nephritis, and hepatitis. Resolution occurred with discontinuation of salicylazosulfapyridine. Although similar reactions have been reported with the antimicrobial sulfonamides, none has been fully described with salicylazosulfapyridine, a combination of a sulfonamide and salicylate."}
{"id": "PMID:27156", "title": "[The myocardiopathies of dermatomyositis and periarteritis nodosa].", "content": "Myocardial involvement was indicated by isolated findings (especially on the ECG) without corresponding functional disorders in one third of cases of dermatomyositis. Rapidly fatal heart failure occurred rarely in this disease, and was noteworthy for a QS complex in the central precordial leads, and for the presence of intracardiac thromboses which could give rise to emboli. Terminal cardiac failure was the rule in cases of periarteritis nodosa, which is a much rarer disease; this occurrence was secondary to hypertension. The most characteristic lesions were nodular coronary arteritis and disseminated myocarditis due to the arteriolar lesions.", "contents": "[The myocardiopathies of dermatomyositis and periarteritis nodosa]. Myocardial involvement was indicated by isolated findings (especially on the ECG) without corresponding functional disorders in one third of cases of dermatomyositis. Rapidly fatal heart failure occurred rarely in this disease, and was noteworthy for a QS complex in the central precordial leads, and for the presence of intracardiac thromboses which could give rise to emboli. Terminal cardiac failure was the rule in cases of periarteritis nodosa, which is a much rarer disease; this occurrence was secondary to hypertension. The most characteristic lesions were nodular coronary arteritis and disseminated myocarditis due to the arteriolar lesions."}
{"id": "PMID:27158", "title": "Experiments on the preparations and testing of associated vaccine against foot and mouth disease and vesicular disease in swine.", "content": "Tests for associated immunization of swine against Foot and Mouth Disease (FMD) and Vesicular Disease (SVD) of swine were carried out. As a result of this investigation, it was established that the prepared and tested inactivated oil vaccine is harmless and immunogenic in sensitive animals. In investigating the course of immunity, the presence of antibody against both antigens was demonstrated in vaccinated animals. All once-vaccinated animals were defended against the virus of SVD during challenge, and 75% of them were defended against FMD. After revaccination, all immunized swine were defended against infection with both viruses. The question of the quality of the associated vaccine and the possibilities of its massive use in industrial swine rearing was discussed.", "contents": "Experiments on the preparations and testing of associated vaccine against foot and mouth disease and vesicular disease in swine. Tests for associated immunization of swine against Foot and Mouth Disease (FMD) and Vesicular Disease (SVD) of swine were carried out. As a result of this investigation, it was established that the prepared and tested inactivated oil vaccine is harmless and immunogenic in sensitive animals. In investigating the course of immunity, the presence of antibody against both antigens was demonstrated in vaccinated animals. All once-vaccinated animals were defended against the virus of SVD during challenge, and 75% of them were defended against FMD. After revaccination, all immunized swine were defended against infection with both viruses. The question of the quality of the associated vaccine and the possibilities of its massive use in industrial swine rearing was discussed."}
{"id": "PMID:27159", "title": "[Properties and isozymes of acid and alkaline phosphatase in cattle testes and endometrium].", "content": "The activity of acid phosphatase in the testicular parenchyma of cattle was found to be higher than that in the endometrium. The acid phosphatase of either tissue broke up p-nitrophenylphosphate at a rate twice as high as that reached for di-sodium phenylphosphate. Hydrolysis of phenolphthalein diphosphate was slower and that of beta-glycerophosphate very slow. Two optimum pH values and two isozymes were recordable from acid phosphatase in testicular supernatant and three optimum pH values as well as three isozymes from that in endometrial supernatant. Even concentrations pf 0.2 mM of copper and mercury ions were strongly inhibiting the acid phosphatase, whereas lead and cadmium ions proved less effective. The activity of acid phosphatase from testes dropped by 24 per cent and that from the endometrium by 16 per cent over eight weeks of storage at -20 degrees C. The average activity of alkaline phosphatase in the endometrium was much higher than that in testicular parenchyma. Alkaline phosphatase from testes exhibited the shortest break-up time for p-nitrophenylphosphate, whereas disodium-phenylphosphate was broken up at the highest rate by endometrial alkaline phosphatase. Two isozymes of alkaline phosphatase were recordable each from the testes and endometrium.", "contents": "[Properties and isozymes of acid and alkaline phosphatase in cattle testes and endometrium]. The activity of acid phosphatase in the testicular parenchyma of cattle was found to be higher than that in the endometrium. The acid phosphatase of either tissue broke up p-nitrophenylphosphate at a rate twice as high as that reached for di-sodium phenylphosphate. Hydrolysis of phenolphthalein diphosphate was slower and that of beta-glycerophosphate very slow. Two optimum pH values and two isozymes were recordable from acid phosphatase in testicular supernatant and three optimum pH values as well as three isozymes from that in endometrial supernatant. Even concentrations pf 0.2 mM of copper and mercury ions were strongly inhibiting the acid phosphatase, whereas lead and cadmium ions proved less effective. The activity of acid phosphatase from testes dropped by 24 per cent and that from the endometrium by 16 per cent over eight weeks of storage at -20 degrees C. The average activity of alkaline phosphatase in the endometrium was much higher than that in testicular parenchyma. Alkaline phosphatase from testes exhibited the shortest break-up time for p-nitrophenylphosphate, whereas disodium-phenylphosphate was broken up at the highest rate by endometrial alkaline phosphatase. Two isozymes of alkaline phosphatase were recordable each from the testes and endometrium."}
{"id": "PMID:27160", "title": "[Relationship between the limbic system and gonadal function. 3. Quantifiable prepuberal morphokinesis of the basolateral amygdaloid body and the ventral hippocampus formation].", "content": "In juvenile female rats the neurons of the limbic system which are attached to the basolateral amygdaloid nucleus and to a circumscribed area of ventral hippocampal formation are characterised by markedly quantifiable morphokinesis between the 21st day of age and onset of the first oestrus. This morphokinesis will take the form of consecutively occurring highly significant volume alterations of the cell nuclei which, in turn, reflect variation in neuronal activity. Some of such variation represents a expression of the general maturation and differentiation of central nervous neurons. The time of occurrence of such variation as well as its peculiar nature also appear to suggest the existence of some special relationship to sexual maturation. This seems to support the conclusion that the basolateral amygdaloid nucleus and the ventral hippocampal formation are attached to the extrahypothalamic central nervous structures of the cerebro-hypophyseal-gonadal axis, in addition to the medial and cortical amygdaloid nuclei. However, the very nature of relationships that may exist between the two investigated components of the limbic system, on the one hand, and sexual maturation as well as gonadal function, on the other, cannot be derived from the results reported in this paper.", "contents": "[Relationship between the limbic system and gonadal function. 3. Quantifiable prepuberal morphokinesis of the basolateral amygdaloid body and the ventral hippocampus formation]. In juvenile female rats the neurons of the limbic system which are attached to the basolateral amygdaloid nucleus and to a circumscribed area of ventral hippocampal formation are characterised by markedly quantifiable morphokinesis between the 21st day of age and onset of the first oestrus. This morphokinesis will take the form of consecutively occurring highly significant volume alterations of the cell nuclei which, in turn, reflect variation in neuronal activity. Some of such variation represents a expression of the general maturation and differentiation of central nervous neurons. The time of occurrence of such variation as well as its peculiar nature also appear to suggest the existence of some special relationship to sexual maturation. This seems to support the conclusion that the basolateral amygdaloid nucleus and the ventral hippocampal formation are attached to the extrahypothalamic central nervous structures of the cerebro-hypophyseal-gonadal axis, in addition to the medial and cortical amygdaloid nuclei. However, the very nature of relationships that may exist between the two investigated components of the limbic system, on the one hand, and sexual maturation as well as gonadal function, on the other, cannot be derived from the results reported in this paper."}
{"id": "PMID:27161", "title": "[Blood acid-base status in fattening pigs in exhausting physical stress of high intensity].", "content": "Reported in this paper are changes in the acid-base state and lactic concentration of blood and muscle samples taken from 28 pigs prior to, during, and after high-intensity exhausting stress applied at ambient temperatures between 17 degrees C and 21 degrees C and at 35 degrees C. Close correlations were found to exist between acid-base states, on the one hand, and lactic acid concentrations, on the other. The lactic acid concentrations reached in blood plasma were between 30 and 40 mHol/1, pH being below 7.0 and BE values being smaller than -22 mHol/1. Close relationships were established between the lactic acid concentration of venous blood plasma, blood pH, and the pH of the musculus longissimus dorsi. Respiratory compensation was of minor importance with ambient temperatures between 17 degrees C and 21 degrees C, but it was of considerable effectiveness at 35 degrees C.", "contents": "[Blood acid-base status in fattening pigs in exhausting physical stress of high intensity]. Reported in this paper are changes in the acid-base state and lactic concentration of blood and muscle samples taken from 28 pigs prior to, during, and after high-intensity exhausting stress applied at ambient temperatures between 17 degrees C and 21 degrees C and at 35 degrees C. Close correlations were found to exist between acid-base states, on the one hand, and lactic acid concentrations, on the other. The lactic acid concentrations reached in blood plasma were between 30 and 40 mHol/1, pH being below 7.0 and BE values being smaller than -22 mHol/1. Close relationships were established between the lactic acid concentration of venous blood plasma, blood pH, and the pH of the musculus longissimus dorsi. Respiratory compensation was of minor importance with ambient temperatures between 17 degrees C and 21 degrees C, but it was of considerable effectiveness at 35 degrees C."}
{"id": "PMID:27162", "title": "[Studies on diarrhea of young calves. 1. Quantitative analysis of the gastrointestinal flora in clinically healthy calves and in calves with diarrhea].", "content": "Quantitative composition of gastro-intestinal-flora was determined in 23 clinically healthy calves and the course of germ spreading was followed up. In comparison with these healthy animals in 25 diarrhoea affected calves at the age of 4 to 17 days there could be observed signigicant differences only in few parts of the gastro-intestinal-tract concerning the quantitative composition of germ flora. Only in 3 animals enterotoxin producing E coli strains could be detected.", "contents": "[Studies on diarrhea of young calves. 1. Quantitative analysis of the gastrointestinal flora in clinically healthy calves and in calves with diarrhea]. Quantitative composition of gastro-intestinal-flora was determined in 23 clinically healthy calves and the course of germ spreading was followed up. In comparison with these healthy animals in 25 diarrhoea affected calves at the age of 4 to 17 days there could be observed signigicant differences only in few parts of the gastro-intestinal-tract concerning the quantitative composition of germ flora. Only in 3 animals enterotoxin producing E coli strains could be detected."}
{"id": "PMID:27163", "title": "Stabilization of human fibroblast interferon purified on concanavalin A-agarose.", "content": "Human fibroblast interferon, obtained by chromatography on concanavalin A-agarose, was stable for at least a month in 30--50 per cent ethylene glycol at 4 degrees, --20 degrees, and --70 degrees C. The succinct point of the present finding is that human fibroblast interferon may be stabilized by ethylene glycol alone without the addition of bovine serum albumin and 'back-contamination' of the interferon preparation.", "contents": "Stabilization of human fibroblast interferon purified on concanavalin A-agarose. Human fibroblast interferon, obtained by chromatography on concanavalin A-agarose, was stable for at least a month in 30--50 per cent ethylene glycol at 4 degrees, --20 degrees, and --70 degrees C. The succinct point of the present finding is that human fibroblast interferon may be stabilized by ethylene glycol alone without the addition of bovine serum albumin and 'back-contamination' of the interferon preparation."}
{"id": "PMID:27164", "title": "Inhibition of thermogenic drinking by beta-adrenergic antagonists.", "content": "The thirst induced by transfer of rats from air at 5 degrees C to air at 25 degrees C (thermogenic drink) was inhibited by d,1-, but not d-propranolol (6 mg/kg body weight) administered 0.5 h prior to removal from cold. The thermogenic drink was not inhibited by a similar administration of the beta1-adrenergic antagonist, practolol (50 and 150 mg/kg body weight), but was inhibited by the beta2-adrenergic antagonist, butoxamine (35 mg/kg body weight). The results are consistent with the suggestion that beta2-adrenergic receptors play a role in mediation of the thermogenic drink in rats.", "contents": "Inhibition of thermogenic drinking by beta-adrenergic antagonists. The thirst induced by transfer of rats from air at 5 degrees C to air at 25 degrees C (thermogenic drink) was inhibited by d,1-, but not d-propranolol (6 mg/kg body weight) administered 0.5 h prior to removal from cold. The thermogenic drink was not inhibited by a similar administration of the beta1-adrenergic antagonist, practolol (50 and 150 mg/kg body weight), but was inhibited by the beta2-adrenergic antagonist, butoxamine (35 mg/kg body weight). The results are consistent with the suggestion that beta2-adrenergic receptors play a role in mediation of the thermogenic drink in rats."}
{"id": "PMID:27167", "title": "The effects of acridine orange on deoxyribonucleic acid in Escherichia coli.", "content": "1. Acridine Orange inhibits growth of Escherichia coli K12 when incubated at pH 7.9, but not at pH 7.4.2. At a non-permissive temperature for DNA polymerase I, Acridine Orange inhibits growth of a temperature-sensitive strain and also increases the rate of elimination of the F'-Lac plasmid. 3. DNA isolated from cells treated with Acridine Orange under conditions that inhibit growth contains material of low molecular weight, which is absent from DNA isolated from cells treated under conditions in which growth is not impaired. 4. Cells incubated with Acridine Orange at both pH 7.4 and 7.9 suffer degradation of DNA, as shown by loss of labelled DNA from the acid-insoluble fraction, which is not observed with untreated cells at either pH. 5. The results suggest that elimination of the F'-Lac plasmid by Acridine Orange requires inactivation of repair processes.", "contents": "The effects of acridine orange on deoxyribonucleic acid in Escherichia coli. 1. Acridine Orange inhibits growth of Escherichia coli K12 when incubated at pH 7.9, but not at pH 7.4.2. At a non-permissive temperature for DNA polymerase I, Acridine Orange inhibits growth of a temperature-sensitive strain and also increases the rate of elimination of the F'-Lac plasmid. 3. DNA isolated from cells treated with Acridine Orange under conditions that inhibit growth contains material of low molecular weight, which is absent from DNA isolated from cells treated under conditions in which growth is not impaired. 4. Cells incubated with Acridine Orange at both pH 7.4 and 7.9 suffer degradation of DNA, as shown by loss of labelled DNA from the acid-insoluble fraction, which is not observed with untreated cells at either pH. 5. The results suggest that elimination of the F'-Lac plasmid by Acridine Orange requires inactivation of repair processes."}
{"id": "PMID:27168", "title": "Electron-paramagnetic-resonance studies on nitrate reductase from Escherichia coli K12.", "content": "Nitrate reductase was purified from anaerobically grown Escherichia coli K12 by a method based on the Triton X-100 extraction procedure of Clegg[(1976) Biochem. J.153, 533-541], but hydrophobic interaction chromatography was used in the final stage. E.p.r. spectra obtained from the enzyme under a variety of conditions are well resolved and were interpreted with the help of the computer-simulation procedures of Lowe [(1978) Biochem. J.171, 649-651]. Parameters for five molybdenum(V) species from the enzyme are given. The low-pH species (g(av.) 1.9827) is in pH-dependent equilibrium with the high-pH species (g(av.) 1.9762), the pK for interconversion of the species being 8.26. Of a variety of anions tested, only nitrate and nitrite formed complexes with the enzyme (in the low-pH form), giving modified molybdenum(V) e.p.r. spectra. These complexes, as well as the low-pH form of the free enzyme, showed interaction of molybdenum with a single exchangeable proton. The fifth molybdenum(V) species, sometimes detected in small amounts, appears not to be due to functional nitrate reductase. After full reduction of the enzyme with dithionite, addition of nitrate caused reoxidation of molybdenum to the quinquivalent state, in a time less than the enzyme turnover. Activity of the enzyme in the pH range 6-10 is controlled by a pK of 8.2. It is suggested that the low-pH signal-giving species is the form of the enzyme involved in the catalytic cycle. Iron-sulphur and other e.p.r. signals from the enzyme are briefly described and the enzymic reaction mechanism is discussed.", "contents": "Electron-paramagnetic-resonance studies on nitrate reductase from Escherichia coli K12. Nitrate reductase was purified from anaerobically grown Escherichia coli K12 by a method based on the Triton X-100 extraction procedure of Clegg[(1976) Biochem. J.153, 533-541], but hydrophobic interaction chromatography was used in the final stage. E.p.r. spectra obtained from the enzyme under a variety of conditions are well resolved and were interpreted with the help of the computer-simulation procedures of Lowe [(1978) Biochem. J.171, 649-651]. Parameters for five molybdenum(V) species from the enzyme are given. The low-pH species (g(av.) 1.9827) is in pH-dependent equilibrium with the high-pH species (g(av.) 1.9762), the pK for interconversion of the species being 8.26. Of a variety of anions tested, only nitrate and nitrite formed complexes with the enzyme (in the low-pH form), giving modified molybdenum(V) e.p.r. spectra. These complexes, as well as the low-pH form of the free enzyme, showed interaction of molybdenum with a single exchangeable proton. The fifth molybdenum(V) species, sometimes detected in small amounts, appears not to be due to functional nitrate reductase. After full reduction of the enzyme with dithionite, addition of nitrate caused reoxidation of molybdenum to the quinquivalent state, in a time less than the enzyme turnover. Activity of the enzyme in the pH range 6-10 is controlled by a pK of 8.2. It is suggested that the low-pH signal-giving species is the form of the enzyme involved in the catalytic cycle. Iron-sulphur and other e.p.r. signals from the enzyme are briefly described and the enzymic reaction mechanism is discussed."}
{"id": "PMID:27169", "title": "Oxygen-binding characteristics of three extracellular haemoglobins of Artemia salina.", "content": "The oxygen-binding characteristics of the three extracellular haemoglobins of brine shrimp (Artemia salina) were studied in vitro by using highly purified preparations. Haemoglobin I is induced last in the development of brine shrimps when functional gills are formed. It has the lowest oxygen affinity (p(50) 5.34mmHg), an intermediate Bohr effect (\u00f8 -0.09 at 20 degrees C) above pH8 and a temperature-sensitivity (DeltaH -44.8 to -45.6kJ/mol at pH8-9) comparable with those observed with other invertebrate haemoglobins [Weber & Heidemann (1977) Comp. Biochem. Physiol. A57, 151-155]. Haemoglobin II, which is the first to be induced, soon after hatching of nauplius larvae, persists generally throughout the whole adult life. It has an intermediate oxygen affinity (p(50) 3.7mmHg), the highest Bohr effect (\u00f8 -0.21 at 20 degrees C) above pH8 and a similar temperature-sensitivity (DeltaH -46.0 to -54.8kJ/mol at pH8-9) as haemoglobin I. However, haemoglobin III, which is induced second several hours after the induction of haemoglobin II but disappearing from the haemolymph in the middle of adult life, has the highest oxygen affinity (p(50) 1.8mmHg), the lowest Bohr effect (\u00f8 -0.03 at 20 degrees C) above pH8.5 and a high resistance against temperature variation between 10 and 25 degrees C at pH8.5-9 (DeltaH -22.6 to -23.0kJ/mol). At pH7.5-8, haemoglobin III exhibits a similar temperature-sensitivity under 30 degrees C as do other haemoglobins. All three haemoglobins have a rather low co-operativity, with Hill coefficients (h 1.6-1.9 at pH8.5), which are dependent on both pH and temperature. The highest co-operativity was observed at 20 degrees C and pH9 for haemoglobins I and II, whereas it was at 27 degrees C and pH8.5 for haemoglobin III. Thus the oxygen-binding behaviour of haemoglobin III in vitro is significantly different from those of haemoglobins I and II and indicates possibly its specific physiological role in vivo in the adaptive process in the natural environment.", "contents": "Oxygen-binding characteristics of three extracellular haemoglobins of Artemia salina. The oxygen-binding characteristics of the three extracellular haemoglobins of brine shrimp (Artemia salina) were studied in vitro by using highly purified preparations. Haemoglobin I is induced last in the development of brine shrimps when functional gills are formed. It has the lowest oxygen affinity (p(50) 5.34mmHg), an intermediate Bohr effect (\u00f8 -0.09 at 20 degrees C) above pH8 and a temperature-sensitivity (DeltaH -44.8 to -45.6kJ/mol at pH8-9) comparable with those observed with other invertebrate haemoglobins [Weber & Heidemann (1977) Comp. Biochem. Physiol. A57, 151-155]. Haemoglobin II, which is the first to be induced, soon after hatching of nauplius larvae, persists generally throughout the whole adult life. It has an intermediate oxygen affinity (p(50) 3.7mmHg), the highest Bohr effect (\u00f8 -0.21 at 20 degrees C) above pH8 and a similar temperature-sensitivity (DeltaH -46.0 to -54.8kJ/mol at pH8-9) as haemoglobin I. However, haemoglobin III, which is induced second several hours after the induction of haemoglobin II but disappearing from the haemolymph in the middle of adult life, has the highest oxygen affinity (p(50) 1.8mmHg), the lowest Bohr effect (\u00f8 -0.03 at 20 degrees C) above pH8.5 and a high resistance against temperature variation between 10 and 25 degrees C at pH8.5-9 (DeltaH -22.6 to -23.0kJ/mol). At pH7.5-8, haemoglobin III exhibits a similar temperature-sensitivity under 30 degrees C as do other haemoglobins. All three haemoglobins have a rather low co-operativity, with Hill coefficients (h 1.6-1.9 at pH8.5), which are dependent on both pH and temperature. The highest co-operativity was observed at 20 degrees C and pH9 for haemoglobins I and II, whereas it was at 27 degrees C and pH8.5 for haemoglobin III. Thus the oxygen-binding behaviour of haemoglobin III in vitro is significantly different from those of haemoglobins I and II and indicates possibly its specific physiological role in vivo in the adaptive process in the natural environment."}
{"id": "PMID:27170", "title": "Equilibrium binding of coenzymes and substrates to nicotinamide-adenine dinucleotide phosphate-linked isocitrate dehydrogenase from bovine heart mitochondria.", "content": "1. The stoicheiometries and affinities of ligand binding to isocitrate dehydrogenase were studied at pH 7.0, mainly by measuring changes in NADPH and protein fluorescence. 2. The affinity of the enzyme for NADPH is about 100-fold greater than it is for NADP+ in various buffer/salt solutions, and the affinities for both coenzymes are decreased by Mg2+, phosphate and increase in ionic strength. 3. The maximum binding capacity of the dimeric enzyme for NADPH, from coenzyme fluorescence and protein-fluorescence measurements, and also for NADP+, by ultrafiltration, is 2 mol/mol of enzyme. Protein-fluorescence titrations of the enzyme with NADP+ are apparently inconsistent with this conclusion, indicating that the increase in protein fluorescence caused by NADP+ binding is not proportional to fractional saturation of the binding sites. 4. Changes in protein fluorescence caused by changes in ionic strength and by the binding of substrates, Mg2+ or NADP+ (but not NADPH) are relatively slow, suggesting conformation changes. 5. In the presence of Mg2+, the enzyme binds isocitrate very strongly, and 2-oxoglutarate rather weakly. 6. Evidence is presented for the formation of an abortive complex of enzyme-Mg2+-isocitrate-NADPH in which isocitrate and NADPH are bound much more weakly than in their complexes with enzyme and Mg2+ alone. 7. The results are discussed in relation to the interpretation of the kinetic properties of the enzyme and its behaviour in the mitochondrion.", "contents": "Equilibrium binding of coenzymes and substrates to nicotinamide-adenine dinucleotide phosphate-linked isocitrate dehydrogenase from bovine heart mitochondria. 1. The stoicheiometries and affinities of ligand binding to isocitrate dehydrogenase were studied at pH 7.0, mainly by measuring changes in NADPH and protein fluorescence. 2. The affinity of the enzyme for NADPH is about 100-fold greater than it is for NADP+ in various buffer/salt solutions, and the affinities for both coenzymes are decreased by Mg2+, phosphate and increase in ionic strength. 3. The maximum binding capacity of the dimeric enzyme for NADPH, from coenzyme fluorescence and protein-fluorescence measurements, and also for NADP+, by ultrafiltration, is 2 mol/mol of enzyme. Protein-fluorescence titrations of the enzyme with NADP+ are apparently inconsistent with this conclusion, indicating that the increase in protein fluorescence caused by NADP+ binding is not proportional to fractional saturation of the binding sites. 4. Changes in protein fluorescence caused by changes in ionic strength and by the binding of substrates, Mg2+ or NADP+ (but not NADPH) are relatively slow, suggesting conformation changes. 5. In the presence of Mg2+, the enzyme binds isocitrate very strongly, and 2-oxoglutarate rather weakly. 6. Evidence is presented for the formation of an abortive complex of enzyme-Mg2+-isocitrate-NADPH in which isocitrate and NADPH are bound much more weakly than in their complexes with enzyme and Mg2+ alone. 7. The results are discussed in relation to the interpretation of the kinetic properties of the enzyme and its behaviour in the mitochondrion."}
{"id": "PMID:27171", "title": "Transient kinetics of nicotinamide-adenine dinucleotide phosphate-linked isocitrate dehydrogenase from bovine heart mitochondria.", "content": "Pre-steady-state studies of the isocitrate dehydrogenase reaction show that the rate constant for the hydride-transfer step is above 990s-1, and that both subunits of the enzyme are simulataneously active. After the fast formation of NADPH in amounts equivalent to the enzyme subunit concentration, the rate of NADPH formation is equal to the steady-state rate if the enzyme has been preincubated with isocitrate and Mg2+. If the enzyme has been preincubated with NADP+ and Mg2+, in 0.05 M-triethanolamine chloride buffer, pH 7.0, with the addition of 0.1 M-NaCl, the amount of NADPH formed in the fast phase is only 60% of the enzyme subunit concentration, and the turnover rate is at first lower than the steady-state rate. In 0.05 M-triethanolamine chloride buffer, pH 7.0, if the enzyme is preincubated with NADP+ or NADPH, the turnover rate increases 3-fold to reach the steady-state rate after about 5 s. Preincubation of the enzyme with isocitrate and Mg2+ abolishes this lag phase, the steady-state rate being reached at once. It is suggested that the enzyme exists in at least two conformational forms with different activities, and that the lag phase represents the transition (k = 0.4s-1) from a form with low activity to the fully active enzyme, induced by the binding of isocitrate and Mg2+.", "contents": "Transient kinetics of nicotinamide-adenine dinucleotide phosphate-linked isocitrate dehydrogenase from bovine heart mitochondria. Pre-steady-state studies of the isocitrate dehydrogenase reaction show that the rate constant for the hydride-transfer step is above 990s-1, and that both subunits of the enzyme are simulataneously active. After the fast formation of NADPH in amounts equivalent to the enzyme subunit concentration, the rate of NADPH formation is equal to the steady-state rate if the enzyme has been preincubated with isocitrate and Mg2+. If the enzyme has been preincubated with NADP+ and Mg2+, in 0.05 M-triethanolamine chloride buffer, pH 7.0, with the addition of 0.1 M-NaCl, the amount of NADPH formed in the fast phase is only 60% of the enzyme subunit concentration, and the turnover rate is at first lower than the steady-state rate. In 0.05 M-triethanolamine chloride buffer, pH 7.0, if the enzyme is preincubated with NADP+ or NADPH, the turnover rate increases 3-fold to reach the steady-state rate after about 5 s. Preincubation of the enzyme with isocitrate and Mg2+ abolishes this lag phase, the steady-state rate being reached at once. It is suggested that the enzyme exists in at least two conformational forms with different activities, and that the lag phase represents the transition (k = 0.4s-1) from a form with low activity to the fully active enzyme, induced by the binding of isocitrate and Mg2+."}
{"id": "PMID:27172", "title": "Purification and some properties of an alkaline proteinase from rat skeletal muscle.", "content": "1. Rat skeletal muscle was homogenized in 0.05M-Tris/HCl, pH 8.5, containing 1M-KCl. Myofibrillar proteins were precipitated by addition of (NH4)2SO4 (33% saturation). 2. The alkaline proteolytic activity that was precipitated with the myofibrillar proteins was solubilized with trypsin (conjugated to Sepharose) and further purified by affinity chromatography, ion-exchange chromatography and gel filtration. 3. The purified enzyme migrates as a single band in polyacrylamide-disc electrophoresis, and has optimum hydrolytic activity with azocasein and [14C]haemoglobin as substrates at pH 9.4 and 9.6 respectively. Its apparent molecular weight, as determined by gel filtration on Sephadex G-75, is 30800. 4. The purified alkaline proteinase is strongly inhibited by equimolar amounts of soya-bean trypsin inhibitor and ovomucoid, whereas di-isopropyl phosphorofluoidate and alpha-toluenesulphonyl fluoride have no effect. On the other hand N-ethylmaleimide and p-chloromercuribenzoate have inhibitory effects on the enzyme activity. 5. Bivalent metal ions (Fe2+, Co2+, Zn2+, Mg2+, Mn2+) diminish the proteolytic activity, at 1mM concentrations. Ca2+ ions and the metal-ion-chelating agent EDTA are without effect on enzyme activity. 6. The enzyme is part of the alkaline proteolytic activity that appears to be associated with myofibrillar proteins.", "contents": "Purification and some properties of an alkaline proteinase from rat skeletal muscle. 1. Rat skeletal muscle was homogenized in 0.05M-Tris/HCl, pH 8.5, containing 1M-KCl. Myofibrillar proteins were precipitated by addition of (NH4)2SO4 (33% saturation). 2. The alkaline proteolytic activity that was precipitated with the myofibrillar proteins was solubilized with trypsin (conjugated to Sepharose) and further purified by affinity chromatography, ion-exchange chromatography and gel filtration. 3. The purified enzyme migrates as a single band in polyacrylamide-disc electrophoresis, and has optimum hydrolytic activity with azocasein and [14C]haemoglobin as substrates at pH 9.4 and 9.6 respectively. Its apparent molecular weight, as determined by gel filtration on Sephadex G-75, is 30800. 4. The purified alkaline proteinase is strongly inhibited by equimolar amounts of soya-bean trypsin inhibitor and ovomucoid, whereas di-isopropyl phosphorofluoidate and alpha-toluenesulphonyl fluoride have no effect. On the other hand N-ethylmaleimide and p-chloromercuribenzoate have inhibitory effects on the enzyme activity. 5. Bivalent metal ions (Fe2+, Co2+, Zn2+, Mg2+, Mn2+) diminish the proteolytic activity, at 1mM concentrations. Ca2+ ions and the metal-ion-chelating agent EDTA are without effect on enzyme activity. 6. The enzyme is part of the alkaline proteolytic activity that appears to be associated with myofibrillar proteins."}
{"id": "PMID:27198", "title": "Association of defective feedback suppressor T cell activity with autoimmunity in NZB mice.", "content": "A \"feedback suppressor T cell\" highly dependent on signals from Ly 1 T helper cells for activation is described. The signal from the Ly 1 cell binds to Fc-like receptors on macrophage membranes. The feedback suppressor cell expresses all three Ly antigens as well as the Qa 1 antigen on its surface, is very sensitive to low doses of cyclophosphamide, disappears relatively rapidly after adult thymectomy, and cannot be demonstrated in NZB mice 6 weeks or older.", "contents": "Association of defective feedback suppressor T cell activity with autoimmunity in NZB mice. A \"feedback suppressor T cell\" highly dependent on signals from Ly 1 T helper cells for activation is described. The signal from the Ly 1 cell binds to Fc-like receptors on macrophage membranes. The feedback suppressor cell expresses all three Ly antigens as well as the Qa 1 antigen on its surface, is very sensitive to low doses of cyclophosphamide, disappears relatively rapidly after adult thymectomy, and cannot be demonstrated in NZB mice 6 weeks or older."}
{"id": "PMID:27203", "title": "Some clinical pharmacological studies with terfenadine, a new antihistamine drug.", "content": "1 A double-blind cross-over trial between placebo, chlorpheniramine, and terfenadine, a new antihistamine drug, was performed in healthy male volunteers to determine and compare their CNS and autonomic effects. 2 Terfenadine and chlorpheniramine were administered orally in therapeutic doses. 3 In objective tests of critical flicker frequency, pursuit rotor, reaction time, salivary volume and pupillary diameter, no statistically significant difference was observed between the treatments. 4 On analogue rating scales, chlorpheniramine produced a statistically significant (P less than 0.05) degree of sedation and impaired concentration as compared to placebo and terfenadine. 5 The results obtained in analogue rating scales were not normally distributed and, therefore, use of non-parametric statistical methods for analysis of such data is strongly advocated.", "contents": "Some clinical pharmacological studies with terfenadine, a new antihistamine drug. 1 A double-blind cross-over trial between placebo, chlorpheniramine, and terfenadine, a new antihistamine drug, was performed in healthy male volunteers to determine and compare their CNS and autonomic effects. 2 Terfenadine and chlorpheniramine were administered orally in therapeutic doses. 3 In objective tests of critical flicker frequency, pursuit rotor, reaction time, salivary volume and pupillary diameter, no statistically significant difference was observed between the treatments. 4 On analogue rating scales, chlorpheniramine produced a statistically significant (P less than 0.05) degree of sedation and impaired concentration as compared to placebo and terfenadine. 5 The results obtained in analogue rating scales were not normally distributed and, therefore, use of non-parametric statistical methods for analysis of such data is strongly advocated."}
{"id": "PMID:27204", "title": "Performance studies with antihistamines.", "content": "1 Effect of four antihistamines, chlorpheniramine (4 mg), clemastine (1 mg), promethazine (10 mg) and terfenadine (60 mg), on visuo-motor coordination and on subjective assessments of performance and well-being were compared with placebo in six healthy females from 0.5--7.0 h after morning ingestion of each drug. The study was double-blind, and the doses used were believed to be equally potent in their antihistaminic activity. 2 There was impaired performance 1.5 h (P less than 0.01) after chlorpheniramine, 3.0 h (P less than 0.05) and 5.0 h (P less than 0.01) after clemastine, and 3.0 h (P less than 0.01) and 5.0 h (P less than 0.001) after promethazine. It was not possible to establish effects on performance after ingestion of terfenadine. Subjective assessments of performance were not altered. 3 The subjects as a group reported improved alertness (P less than 0.05) and improved wakefulness (P less than 0.05) 0.5 h and 3.5 h respectively after ingestion of terfenadine, and were less energetic (P less than 0.05) 7.0 h after ingestion of chlorpheniramine. There were not other consistent changes in assessments of well-being.", "contents": "Performance studies with antihistamines. 1 Effect of four antihistamines, chlorpheniramine (4 mg), clemastine (1 mg), promethazine (10 mg) and terfenadine (60 mg), on visuo-motor coordination and on subjective assessments of performance and well-being were compared with placebo in six healthy females from 0.5--7.0 h after morning ingestion of each drug. The study was double-blind, and the doses used were believed to be equally potent in their antihistaminic activity. 2 There was impaired performance 1.5 h (P less than 0.01) after chlorpheniramine, 3.0 h (P less than 0.05) and 5.0 h (P less than 0.01) after clemastine, and 3.0 h (P less than 0.01) and 5.0 h (P less than 0.001) after promethazine. It was not possible to establish effects on performance after ingestion of terfenadine. Subjective assessments of performance were not altered. 3 The subjects as a group reported improved alertness (P less than 0.05) and improved wakefulness (P less than 0.05) 0.5 h and 3.5 h respectively after ingestion of terfenadine, and were less energetic (P less than 0.05) 7.0 h after ingestion of chlorpheniramine. There were not other consistent changes in assessments of well-being."}
{"id": "PMID:27205", "title": "The acute effects of the administration of rimiterol aerosol in asthmatic children.", "content": "1 Ten asthmatic children received on two separate occasions rimiterol (500 microgram) and orciprenaline (1.5 mg) as aerosols in a double-blind, crossover design trial. Respiratory parameters (FEV1, FVC and PEFR) and pulse rate were recorded for 60 min after each administration. 2 Rimiterol produced effective bronchodilation in children with negligible cardiac stimulation. It differed from orciprenaline in that the peak bronchodilator effect was not maintained during the 60 min observation period. 3 Rimiterol is a selective, short-acting, sympathomimetic bronchodilator in children.", "contents": "The acute effects of the administration of rimiterol aerosol in asthmatic children. 1 Ten asthmatic children received on two separate occasions rimiterol (500 microgram) and orciprenaline (1.5 mg) as aerosols in a double-blind, crossover design trial. Respiratory parameters (FEV1, FVC and PEFR) and pulse rate were recorded for 60 min after each administration. 2 Rimiterol produced effective bronchodilation in children with negligible cardiac stimulation. It differed from orciprenaline in that the peak bronchodilator effect was not maintained during the 60 min observation period. 3 Rimiterol is a selective, short-acting, sympathomimetic bronchodilator in children."}
{"id": "PMID:27206", "title": "Periarteritis nodosa and thrombotic thrombocytopenic purpura with serous retinal detachment in siblings.", "content": "Periarteritis nodosa and thrombotic thrombocytopenic purpura in siblings is reported. In both patients a localised serous retinal detachment and lesions of the retinal pigment epithelium had developed owing to choroidal vascular obstruction. These cases support the suggested possible relationship between the two conditions.", "contents": "Periarteritis nodosa and thrombotic thrombocytopenic purpura with serous retinal detachment in siblings. Periarteritis nodosa and thrombotic thrombocytopenic purpura in siblings is reported. In both patients a localised serous retinal detachment and lesions of the retinal pigment epithelium had developed owing to choroidal vascular obstruction. These cases support the suggested possible relationship between the two conditions."}
{"id": "PMID:27207", "title": "Gastric secretion in suckling pigs and early-weaned pigs given a dry cow's-mild formula ad lib.", "content": "1. Twelve gastric-cannulated litter-mate pigs were used to study secretion and proteolytic activity in the stomach of suckling and early-weaned pigs in relation to age and food intake. 2. Results demonstrate that from the first observation at day 8, piglets were able to secrete acid. pH and acid concentration did not change during the first 4 weeks of life. 3. Proteolytic activity was low during the first 2--3 weeks of life and rapidly increased thereafter. 4. Two phenomena differentiated suckling pigs from pigs given dry cow's milk: (1) a low buffering capacity the gastric contents, beginning 1 hr after feeding the dry cow's-milk formula, results in a low total acid concentration in the weaned pigs and (2) the increase in proteolytic activity in relation to the age is much more pronounced in the artificially-reared pigs. 5. These two phenomena are discussed and related to the formation of a hard casein clot in the stomach of the cow's-milk-fed pigs, which has a long retention time and stimulates gastrin release.", "contents": "Gastric secretion in suckling pigs and early-weaned pigs given a dry cow's-mild formula ad lib. 1. Twelve gastric-cannulated litter-mate pigs were used to study secretion and proteolytic activity in the stomach of suckling and early-weaned pigs in relation to age and food intake. 2. Results demonstrate that from the first observation at day 8, piglets were able to secrete acid. pH and acid concentration did not change during the first 4 weeks of life. 3. Proteolytic activity was low during the first 2--3 weeks of life and rapidly increased thereafter. 4. Two phenomena differentiated suckling pigs from pigs given dry cow's milk: (1) a low buffering capacity the gastric contents, beginning 1 hr after feeding the dry cow's-milk formula, results in a low total acid concentration in the weaned pigs and (2) the increase in proteolytic activity in relation to the age is much more pronounced in the artificially-reared pigs. 5. These two phenomena are discussed and related to the formation of a hard casein clot in the stomach of the cow's-milk-fed pigs, which has a long retention time and stimulates gastrin release."}
{"id": "PMID:27210", "title": "Studies on the microsomal mixed function oxidase system: redox properties of detergent-solubilized NADPH-cytochrome P-450 reductase.", "content": "Hepatic microsomal NADPH-cytochrome P-450 reductase was solubilized from rabbit liver microsomes in the presence of detergents and purified to homogeneity by column chromatography. The purified reductase had a molecular weight of 78 000 and contained 1 mol each of FAD and FMN per mol of enzyme. On reduction with NADPH in the presence of molecular oxygen, an 02-stable semiquinone containing one flavin free radical per two flavins was formed, in agreement with previous work on purified trypsin-solubilized reductase. The reduction of oxidized enzyme by NADPH, and autoxidation of NADPH-reduced enzyme by air, proceeded by both one-electron equivalent and two-electron equivalent mechanisms. The reductase reduced cytochrome P-450 (from phenobarbital-treated rabbits) and cytochrome P-448 (from 3-methylcholanthrene-treated rabbits). The rate of reduction of cytochrome P-450 increased in the presence of a substrate, benzphetamine, but that of cytochrome P-448 did not.", "contents": "Studies on the microsomal mixed function oxidase system: redox properties of detergent-solubilized NADPH-cytochrome P-450 reductase. Hepatic microsomal NADPH-cytochrome P-450 reductase was solubilized from rabbit liver microsomes in the presence of detergents and purified to homogeneity by column chromatography. The purified reductase had a molecular weight of 78 000 and contained 1 mol each of FAD and FMN per mol of enzyme. On reduction with NADPH in the presence of molecular oxygen, an 02-stable semiquinone containing one flavin free radical per two flavins was formed, in agreement with previous work on purified trypsin-solubilized reductase. The reduction of oxidized enzyme by NADPH, and autoxidation of NADPH-reduced enzyme by air, proceeded by both one-electron equivalent and two-electron equivalent mechanisms. The reductase reduced cytochrome P-450 (from phenobarbital-treated rabbits) and cytochrome P-448 (from 3-methylcholanthrene-treated rabbits). The rate of reduction of cytochrome P-450 increased in the presence of a substrate, benzphetamine, but that of cytochrome P-448 did not."}
{"id": "PMID:27211", "title": "Reactions of reduced nicotinamide adenine dinucleotide in acid: studies by reversed-phase high-pressure liquid chromatography.", "content": "Reversed-phase high-pressure liquid chromatography was used to isolate acid breakdown products of reduced nicotinamide adenine dinucleotide (NADH) and products produced when NADH breakdown is catalyzed by glyceraldehyde-3-phosphate dehydrogenase (G-3-PD). Chromatographic and UV spectral data on these and related products support a mechanism for NADH acid degradation involving hydroxy addition at the nicotinamide C-6 followed by cyclization of the ring and the adjacent ribose moiety. G-3-PD is shown to catalyze a reaction in which two products are formed which are also intermediates in the acid degradation of NADH (alpha- and beta-6-hydroxynicotinamide products). Formation of the major acid products fits a three-step, first-order mechanism curve, making it possible to calculate the rate constants k2 and k3 as well as the previously determined k1.", "contents": "Reactions of reduced nicotinamide adenine dinucleotide in acid: studies by reversed-phase high-pressure liquid chromatography. Reversed-phase high-pressure liquid chromatography was used to isolate acid breakdown products of reduced nicotinamide adenine dinucleotide (NADH) and products produced when NADH breakdown is catalyzed by glyceraldehyde-3-phosphate dehydrogenase (G-3-PD). Chromatographic and UV spectral data on these and related products support a mechanism for NADH acid degradation involving hydroxy addition at the nicotinamide C-6 followed by cyclization of the ring and the adjacent ribose moiety. G-3-PD is shown to catalyze a reaction in which two products are formed which are also intermediates in the acid degradation of NADH (alpha- and beta-6-hydroxynicotinamide products). Formation of the major acid products fits a three-step, first-order mechanism curve, making it possible to calculate the rate constants k2 and k3 as well as the previously determined k1."}
{"id": "PMID:27212", "title": "Affinity chromatography of H+-translocating adenosine triphosphatase isolated by chloroform extraction of Rhodospirillum rubrum chromatophores. Modification of binding affinity by divalent cations and activating anions.", "content": "1. ATPase isolated from Rhodospirillum rubrum by chloroform extraction and purified by gel filtration or affinity chromatography shows three bands (alpha, beta and gamma) upon electrophoresis in sodium dodecyl sulphate. 2. Ca2+-ATPase activity of the preparation is inhibited by aurovertin and efrapeptin but not by oligomycin. Activity may be inhibited by treatment with 4-chloro-7-nitrobenzofurazan and subsequently restored by dithiothreitol. 3. The enzyme fails to reconstitute photophosphorylation in chromatophores depleted of ATPase by sonic irradiation. 4. Most of the active protein from the crude chloroform extract binds to an affinity chromatography column bearing an immobilised ADP analogue but not to a column bearing immobilised pyrophosphate. 5. In the absence of divalent cations, a component with a very high specific activity for Ca2+-ATPase is eluted from the column by 1.6 mM ATP. This protein migrates asa single band on 5% polyacrylamide gel electrophoresis and only possesses three subunits. At 12 mM ATP an inactive protein is eluted which does not run on acid or alkali polyacrylamide gels and shows a complex subunit structure. 6. ATPase preparations prepared by acetone extraction or by sonic irradiation of chromatophores may also be purified 10-fold by affinity chromatography. 7. The inclusion of 5 mM MgCl2 or CaCl2 during affinity chromatography of chloroform ATPase increases the capacity of the column for the enzyme and demands a higher eluting concentration of ATP. 8. When the enzyme is more than 90% inhibited by efrapeptin or 4-chloro-7-nitrobenzofurazan, the binding characteristics of the enzyme are not affected. 9. 10 mM Na2SO3, which greatly stimulates the Ca2+- and Mg2+-dependent ATPase activity of the enzyme and increases Ki (ADP) for Ca2+-ATPase from 50 to 850 micron, prevents binding to the affinity column. Binding may be restored by the addition of divalent cations. 10. Na2SO3 increases the rate of ATP hydrolysis, ATP-driven H+ translocation and ATP-driven transhydrogenase in chromatophores. 11. It is proposed that anions such as sulphite convert the chromatophore ATPase into a form which is a more efficient energy transducer.", "contents": "Affinity chromatography of H+-translocating adenosine triphosphatase isolated by chloroform extraction of Rhodospirillum rubrum chromatophores. Modification of binding affinity by divalent cations and activating anions. 1. ATPase isolated from Rhodospirillum rubrum by chloroform extraction and purified by gel filtration or affinity chromatography shows three bands (alpha, beta and gamma) upon electrophoresis in sodium dodecyl sulphate. 2. Ca2+-ATPase activity of the preparation is inhibited by aurovertin and efrapeptin but not by oligomycin. Activity may be inhibited by treatment with 4-chloro-7-nitrobenzofurazan and subsequently restored by dithiothreitol. 3. The enzyme fails to reconstitute photophosphorylation in chromatophores depleted of ATPase by sonic irradiation. 4. Most of the active protein from the crude chloroform extract binds to an affinity chromatography column bearing an immobilised ADP analogue but not to a column bearing immobilised pyrophosphate. 5. In the absence of divalent cations, a component with a very high specific activity for Ca2+-ATPase is eluted from the column by 1.6 mM ATP. This protein migrates asa single band on 5% polyacrylamide gel electrophoresis and only possesses three subunits. At 12 mM ATP an inactive protein is eluted which does not run on acid or alkali polyacrylamide gels and shows a complex subunit structure. 6. ATPase preparations prepared by acetone extraction or by sonic irradiation of chromatophores may also be purified 10-fold by affinity chromatography. 7. The inclusion of 5 mM MgCl2 or CaCl2 during affinity chromatography of chloroform ATPase increases the capacity of the column for the enzyme and demands a higher eluting concentration of ATP. 8. When the enzyme is more than 90% inhibited by efrapeptin or 4-chloro-7-nitrobenzofurazan, the binding characteristics of the enzyme are not affected. 9. 10 mM Na2SO3, which greatly stimulates the Ca2+- and Mg2+-dependent ATPase activity of the enzyme and increases Ki (ADP) for Ca2+-ATPase from 50 to 850 micron, prevents binding to the affinity column. Binding may be restored by the addition of divalent cations. 10. Na2SO3 increases the rate of ATP hydrolysis, ATP-driven H+ translocation and ATP-driven transhydrogenase in chromatophores. 11. It is proposed that anions such as sulphite convert the chromatophore ATPase into a form which is a more efficient energy transducer."}
{"id": "PMID:27213", "title": "Synergism of triggered luminescence by simultaneous treatment of pH transition and potassium addition in chloroplasts.", "content": "KCL-induced luminescence in relation to slow delayed light emission (greater than 3 s) and pH shift-triggered luminescence was studied in preilluminated chloroplasts. An activation pathway for KCl-induced luminescence similar to that for acidbase-triggered luminescence but different from that for delayed light emission is suggested. When the chloroplasts were subjected to a small amount of pH transition together with a simultaneous addition of KCl, a synergistic enhancement of triggered luminescence was observed. The synergism was not observed when the pH transition was increased. The results are interpreted according to the protonation model for stimulated luminescence.", "contents": "Synergism of triggered luminescence by simultaneous treatment of pH transition and potassium addition in chloroplasts. KCL-induced luminescence in relation to slow delayed light emission (greater than 3 s) and pH shift-triggered luminescence was studied in preilluminated chloroplasts. An activation pathway for KCl-induced luminescence similar to that for acidbase-triggered luminescence but different from that for delayed light emission is suggested. When the chloroplasts were subjected to a small amount of pH transition together with a simultaneous addition of KCl, a synergistic enhancement of triggered luminescence was observed. The synergism was not observed when the pH transition was increased. The results are interpreted according to the protonation model for stimulated luminescence."}
{"id": "PMID:27214", "title": "Interaction of fluorinated ether anesthetics with artificial membranes.", "content": "Fluorine-19 nuclear magnetic resonance spectroscopy is applied to the study of the environment of dipalmitoyl phosphatidylcholine-bound fluorinated ether anesthetics (enflurane, fluoroxene and methoxyflurane) both below and above the lipid gel to liquid crystal phase transition temperature. Line widths and spin-lattice relaxation time (T1) measurements are consistent with substantial immobilization of the lipid-bound anesethetic molecules. Heating anesthetic/lipid mixtures above the lipid transition temperature leads to narrowing of the lipid-bound anesthetic fluorine resonances accompanied by little or no change in anesthetic fluorine-19 chemical shifts, suggesting that although the mobility of the bound anesthetic increases at the higher temperature, the nature of the anesthetic-lipid interaction changes little as a result of this phase change. Differential scanning calorimetric studies of the effects of these anesthetics on the phase transition behavior of the phospholipid indicate that the regions of the bilayer in which volatile anesthetics partition at lower concentrations are different from the regions in which they partition at higher concentrations.", "contents": "Interaction of fluorinated ether anesthetics with artificial membranes. Fluorine-19 nuclear magnetic resonance spectroscopy is applied to the study of the environment of dipalmitoyl phosphatidylcholine-bound fluorinated ether anesthetics (enflurane, fluoroxene and methoxyflurane) both below and above the lipid gel to liquid crystal phase transition temperature. Line widths and spin-lattice relaxation time (T1) measurements are consistent with substantial immobilization of the lipid-bound anesethetic molecules. Heating anesthetic/lipid mixtures above the lipid transition temperature leads to narrowing of the lipid-bound anesthetic fluorine resonances accompanied by little or no change in anesthetic fluorine-19 chemical shifts, suggesting that although the mobility of the bound anesthetic increases at the higher temperature, the nature of the anesthetic-lipid interaction changes little as a result of this phase change. Differential scanning calorimetric studies of the effects of these anesthetics on the phase transition behavior of the phospholipid indicate that the regions of the bilayer in which volatile anesthetics partition at lower concentrations are different from the regions in which they partition at higher concentrations."}
{"id": "PMID:27216", "title": "Characterization of two poly(A) polymerases from cultured hamster fibroblasts.", "content": "The enzymatic and physiochemical properties of poly(A) polymerases IIA and IIB from cultured hamster fibroblasts were investigated. The enzymes show an absolute requirement for Mn2+ as the divalent ion. Although Mg2+ alone is inactive, maximum activity is observed in the presence of both Mn2+ and Mg2+. An optimal pH of approx. 8 is found for polymerases IIA and IIB. The enzymes, however, differ somewhat in the pH curves as well as in the Mn2+ and Mg2+ concentration curves. Poly(A) polymerases IIA and IIB have an isoelectric point of about 6 and a sedimentation coefficient of 3.5--4 S. The molecular weights, obtained by gel filtration chromatography, are 145 000 and 155 000 for enzymes IIA and IIB, respectively. Poly(A) polymerases IIA and IIB can utilize a variety of natural and synthetic RNAs as well as DNA as primers. Poly(A) polymerase IIA is saturated at much lower concentrations of primer than enzyme IIB. On the other hand, the chain length of the product synthesized by polymerase IIA is independent of the primer concentration, whereas, with polymerase IIB, the length of the product decreases when the concentration of RNA is increased.", "contents": "Characterization of two poly(A) polymerases from cultured hamster fibroblasts. The enzymatic and physiochemical properties of poly(A) polymerases IIA and IIB from cultured hamster fibroblasts were investigated. The enzymes show an absolute requirement for Mn2+ as the divalent ion. Although Mg2+ alone is inactive, maximum activity is observed in the presence of both Mn2+ and Mg2+. An optimal pH of approx. 8 is found for polymerases IIA and IIB. The enzymes, however, differ somewhat in the pH curves as well as in the Mn2+ and Mg2+ concentration curves. Poly(A) polymerases IIA and IIB have an isoelectric point of about 6 and a sedimentation coefficient of 3.5--4 S. The molecular weights, obtained by gel filtration chromatography, are 145 000 and 155 000 for enzymes IIA and IIB, respectively. Poly(A) polymerases IIA and IIB can utilize a variety of natural and synthetic RNAs as well as DNA as primers. Poly(A) polymerase IIA is saturated at much lower concentrations of primer than enzyme IIB. On the other hand, the chain length of the product synthesized by polymerase IIA is independent of the primer concentration, whereas, with polymerase IIB, the length of the product decreases when the concentration of RNA is increased."}
{"id": "PMID:27217", "title": "The phosphorylation of ribosomal proteins L14 and S3 in Krebs II ascites cells.", "content": "Krebs II ascites cells incubated in Earle's saline (lacking glucose and amino acids) contain ribosomes with proteins S6 and Lgamma phosphorylated, as do ascites cells grown in the peritonea of mice or hamster fibroblasts grown in Eagle's medium. When ascites cells were incubated in Eagle's medium (containing glucose and amino acids) there was extensive glycolysis, producing very acidic conditions, and ribosomal proteins S3 and L14 became phosphorylated whereas Lgamma became dephosphorylated. This altered pattern of phosphorylation could not be produced merely by incubating ascites cells in Earle's saline at a decreased pH, but a rather similar pattern was produced when Earle's saline was supplemented with amino acids (but with glucose still omitted). These results suggest that depriving ascites cells of glucose may induce the synthesis of a protein (or proteins), necessary for alteration of the pattern of phosphorylation of the ribosomal proteins.", "contents": "The phosphorylation of ribosomal proteins L14 and S3 in Krebs II ascites cells. Krebs II ascites cells incubated in Earle's saline (lacking glucose and amino acids) contain ribosomes with proteins S6 and Lgamma phosphorylated, as do ascites cells grown in the peritonea of mice or hamster fibroblasts grown in Eagle's medium. When ascites cells were incubated in Eagle's medium (containing glucose and amino acids) there was extensive glycolysis, producing very acidic conditions, and ribosomal proteins S3 and L14 became phosphorylated whereas Lgamma became dephosphorylated. This altered pattern of phosphorylation could not be produced merely by incubating ascites cells in Earle's saline at a decreased pH, but a rather similar pattern was produced when Earle's saline was supplemented with amino acids (but with glucose still omitted). These results suggest that depriving ascites cells of glucose may induce the synthesis of a protein (or proteins), necessary for alteration of the pattern of phosphorylation of the ribosomal proteins."}
{"id": "PMID:27218", "title": "Protein methylation in animal cells. I. Purification and properties of S-adenosyl-L-methionine:protein (arginine) N-methyltransferase from Krebs II ascites cells.", "content": "1. A protein methylase which specifically transfers methyl groups from S-adenosyl-L-methionine to arginine residues of histones has been substantially purified from Krebs II ascites cells. The purified enzyme was obtained free of contamination by other protein methyl transferases specific for carboxyl and lysine residues. This latter activity copurified with the present enzyme until advanced stages of purification. 2. The purified enzyme does not require any divalent cation for maximum activity. It is inhibited by ionic strength, N-ethylmaleimide and S-adenosyl-L-homocysteine. It has an apparent molecular weight on gel filtration of approx. 5 . 10(5). A Km value for S-adenosyl-L-methionine of 2.5 . 10(-6) M was determined, while the dissociation constant Ki for S-adenosyl-L-homocysteine, which acts as a competitor, was 1.4 . 10(-6) M.", "contents": "Protein methylation in animal cells. I. Purification and properties of S-adenosyl-L-methionine:protein (arginine) N-methyltransferase from Krebs II ascites cells. 1. A protein methylase which specifically transfers methyl groups from S-adenosyl-L-methionine to arginine residues of histones has been substantially purified from Krebs II ascites cells. The purified enzyme was obtained free of contamination by other protein methyl transferases specific for carboxyl and lysine residues. This latter activity copurified with the present enzyme until advanced stages of purification. 2. The purified enzyme does not require any divalent cation for maximum activity. It is inhibited by ionic strength, N-ethylmaleimide and S-adenosyl-L-homocysteine. It has an apparent molecular weight on gel filtration of approx. 5 . 10(5). A Km value for S-adenosyl-L-methionine of 2.5 . 10(-6) M was determined, while the dissociation constant Ki for S-adenosyl-L-homocysteine, which acts as a competitor, was 1.4 . 10(-6) M."}
{"id": "PMID:27219", "title": "Poly(A) polymerases of rat liver nuclei. Purification and specificity.", "content": "Two poly(A) polymerases were isolated from rat liver nuclei and purified more than one thousand times by ion exchange chromatography on DEAE-Sephadex and phosphocellulose columns as well as affinity chromatography on a chromosomal RNA-Sepharose column. One of the two enzymes is bound to chromatin and uses as primer chromosomal RNA, while the second one is localized in the nucleoplasm and uses as primer poly(A) and hnRNA isolated from chromatin. The two enzymes seem to participate in the polyadenylation of chromosomal RNA in vitro, by a coupled mechanism. According to this mechanism, the chromatin bound enzyme adds 120-130 adenosine nucleotides to chromosomal RNA and consequently the nucleoplasmic enzyme completes the poly-adenylation by adding 80-90 more AMP units to the polyadenylated end of chromosomal RNA.", "contents": "Poly(A) polymerases of rat liver nuclei. Purification and specificity. Two poly(A) polymerases were isolated from rat liver nuclei and purified more than one thousand times by ion exchange chromatography on DEAE-Sephadex and phosphocellulose columns as well as affinity chromatography on a chromosomal RNA-Sepharose column. One of the two enzymes is bound to chromatin and uses as primer chromosomal RNA, while the second one is localized in the nucleoplasm and uses as primer poly(A) and hnRNA isolated from chromatin. The two enzymes seem to participate in the polyadenylation of chromosomal RNA in vitro, by a coupled mechanism. According to this mechanism, the chromatin bound enzyme adds 120-130 adenosine nucleotides to chromosomal RNA and consequently the nucleoplasmic enzyme completes the poly-adenylation by adding 80-90 more AMP units to the polyadenylated end of chromosomal RNA."}
{"id": "PMID:27220", "title": "Inhibition of ribonuclease. Efficacy of sodium dodecyl sulfate, diethyl pyrocarbonate, protein ase K and heparin using a sensitive ribonuclease assay.", "content": "The effectiveness of several commonly used inhibitors of ribonuclease (RNAase) has been studied using the removal of radio-labelled leucine from leucyl-tRNA as a sensitive assay for RNAase activity. The inhibitors were tested under a variety of conditions, varying the temperature, the pH, and the source of RNAase. When each inhibitor is udes separately in the presence of pancreatic RNAase, sodium dodecyl sulfate (SDS) is the most effective; but during long exposures to temperatures above 0 degrees C considerable amounts of RNA  are still degraded. Combination of inhibitors are more effective in preserving RNA; with this assay, a combination of SDS with diethyl pyrocarbonate is the most effective. Proteinase K acts as an inhibitor when used in combination with SDS; however, it has RNAase activity when used by itself. Diethyl pyrocarbonate, when used at the high range of concentrations employed by others for RNAase inhibition, reacts with RNA changing its charge. However, when diethyl pyrocarbonate is used in smaller amounts the effects on RNA are minimal, and when used in combination with SDS it effectively inhibits RNAase.", "contents": "Inhibition of ribonuclease. Efficacy of sodium dodecyl sulfate, diethyl pyrocarbonate, protein ase K and heparin using a sensitive ribonuclease assay. The effectiveness of several commonly used inhibitors of ribonuclease (RNAase) has been studied using the removal of radio-labelled leucine from leucyl-tRNA as a sensitive assay for RNAase activity. The inhibitors were tested under a variety of conditions, varying the temperature, the pH, and the source of RNAase. When each inhibitor is udes separately in the presence of pancreatic RNAase, sodium dodecyl sulfate (SDS) is the most effective; but during long exposures to temperatures above 0 degrees C considerable amounts of RNA  are still degraded. Combination of inhibitors are more effective in preserving RNA; with this assay, a combination of SDS with diethyl pyrocarbonate is the most effective. Proteinase K acts as an inhibitor when used in combination with SDS; however, it has RNAase activity when used by itself. Diethyl pyrocarbonate, when used at the high range of concentrations employed by others for RNAase inhibition, reacts with RNA changing its charge. However, when diethyl pyrocarbonate is used in smaller amounts the effects on RNA are minimal, and when used in combination with SDS it effectively inhibits RNAase."}
{"id": "PMID:27221", "title": "Intramembraneous localization of rat liver microsomal hexose-6-phosphate dehydrogenase and membrane permeability to its substrates.", "content": "A method for purifying hexose-6-phosphate dehydrogenase (beta-D-glucose: NAD(P) -oxidoreductase, EC 1.1.1.47) from rat liver microsomes is described. The purified enzyme was shown to be homogeneous by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. It is shown that the enzyme is bound to the inner surface of microsomal membranes, and that glucose 6-phosphate, but not NADP, penetrates almost freely into the membranes at 37 degrees C.", "contents": "Intramembraneous localization of rat liver microsomal hexose-6-phosphate dehydrogenase and membrane permeability to its substrates. A method for purifying hexose-6-phosphate dehydrogenase (beta-D-glucose: NAD(P) -oxidoreductase, EC 1.1.1.47) from rat liver microsomes is described. The purified enzyme was shown to be homogeneous by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. It is shown that the enzyme is bound to the inner surface of microsomal membranes, and that glucose 6-phosphate, but not NADP, penetrates almost freely into the membranes at 37 degrees C."}
{"id": "PMID:27223", "title": "Binding of m-nitrobenzeneboronic acid to the active site of subtilisin BPN.", "content": "m-Nitrobenzeneboronic acid as a possible transition-state analog for serine proteases was found to cause absorption spectral change from 250 nm 350 nm upon binding with subtilisin BPN' (EC 3.4.21.14) at pH 6.5. Similar difference spectral changes of m-nitrobenzeneboronic acid were also observed at alkaline pH or upon addition of N-methylimidazole at pH 6.5. A characteristic circular dichroism spectrum of m-nitrobenezeneboronic acid was induced upon binding with subtilisin BPN' not only at pH 6.5, but also at alkaline pH. Circular dichroism spectral titration confirmed the stoichiometry of 1 : 1 for the m-nitrobenzeneboronic acid - subtilisin complex. m-Nitrobenzeneboronic acid was shown to be useful as a reversible chromophoric probe for the catalytic site of serine proteases.", "contents": "Binding of m-nitrobenzeneboronic acid to the active site of subtilisin BPN. m-Nitrobenzeneboronic acid as a possible transition-state analog for serine proteases was found to cause absorption spectral change from 250 nm 350 nm upon binding with subtilisin BPN' (EC 3.4.21.14) at pH 6.5. Similar difference spectral changes of m-nitrobenzeneboronic acid were also observed at alkaline pH or upon addition of N-methylimidazole at pH 6.5. A characteristic circular dichroism spectrum of m-nitrobenezeneboronic acid was induced upon binding with subtilisin BPN' not only at pH 6.5, but also at alkaline pH. Circular dichroism spectral titration confirmed the stoichiometry of 1 : 1 for the m-nitrobenzeneboronic acid - subtilisin complex. m-Nitrobenzeneboronic acid was shown to be useful as a reversible chromophoric probe for the catalytic site of serine proteases."}
{"id": "PMID:27224", "title": "Excitation of indole-3-acetic acid (an auxin) in a linoleate-lipoxygenase system.", "content": "The weak luminescence that accompanies the linoleate-lipoxygenase reaction was greatly enhanced by the addition of indole analogues, and especially indole acetic acid. The main emitting species in the indole acetic acid-linoleate-lipoxygenase system was analysed spectrophotometrically in the visible region and ascribed to the transition of excited indole acetate in triplet state to its ground state. Such an excited indole acetate could be generated by transfer of energy from the excited CO2 and excited carbonyl (generated by the linoleate-lipoxygenase reaction) to indole acetate in the ground state, but not by cleavage of the dioxetane analog (positions 2 and 3 on the indole ring).", "contents": "Excitation of indole-3-acetic acid (an auxin) in a linoleate-lipoxygenase system. The weak luminescence that accompanies the linoleate-lipoxygenase reaction was greatly enhanced by the addition of indole analogues, and especially indole acetic acid. The main emitting species in the indole acetic acid-linoleate-lipoxygenase system was analysed spectrophotometrically in the visible region and ascribed to the transition of excited indole acetate in triplet state to its ground state. Such an excited indole acetate could be generated by transfer of energy from the excited CO2 and excited carbonyl (generated by the linoleate-lipoxygenase reaction) to indole acetate in the ground state, but not by cleavage of the dioxetane analog (positions 2 and 3 on the indole ring)."}
{"id": "PMID:27225", "title": "Lipid metabolism by The gall-bladder. II. The in vitro conversion of lysophosphatidylcholine to phosphatidylcholine.", "content": "Lysophosphatidylcholine acyltransferase, which catalyzes the acylation of lysophosphatidylcholine with fatty acid coenzyme A to form phosphatidylcholine, was assayed in gall-bladder mucosa. In guinea pig gall-bladder the activity parallels that of the microsomal enzyme, glucose-6-phosphatase with 3--4-fold enrichment of the activity in the microsomes. Studies with saturated and unsaturated substrates demonstrated highest activity when oleoyl coenzyme A and palmitoyl lysophosphatidylcholine were used and the lowest activity when palmitoyl coenzyme A and palmitoyl lysophosphatidylcholine were used. This activity was demonstrated in the dog, rabbit, cat, calf and human gall-bladder mucosa; however, a wide variation in the amount was observed. Lysophospholipase, which catalyzes the hydrolysis of lysophosphatidylcholine to glycerophosphorylcholine and fatty acid, was also demonstrated in gall-bladder mucosa.", "contents": "Lipid metabolism by The gall-bladder. II. The in vitro conversion of lysophosphatidylcholine to phosphatidylcholine. Lysophosphatidylcholine acyltransferase, which catalyzes the acylation of lysophosphatidylcholine with fatty acid coenzyme A to form phosphatidylcholine, was assayed in gall-bladder mucosa. In guinea pig gall-bladder the activity parallels that of the microsomal enzyme, glucose-6-phosphatase with 3--4-fold enrichment of the activity in the microsomes. Studies with saturated and unsaturated substrates demonstrated highest activity when oleoyl coenzyme A and palmitoyl lysophosphatidylcholine were used and the lowest activity when palmitoyl coenzyme A and palmitoyl lysophosphatidylcholine were used. This activity was demonstrated in the dog, rabbit, cat, calf and human gall-bladder mucosa; however, a wide variation in the amount was observed. Lysophospholipase, which catalyzes the hydrolysis of lysophosphatidylcholine to glycerophosphorylcholine and fatty acid, was also demonstrated in gall-bladder mucosa."}
{"id": "PMID:27226", "title": "Sites of direct and indirect halogenation of albumin.", "content": "The sites of radiohalogenation in proteins vary with the labeling method and the pH of the labeling reaciton. We have directly halogenated albumin with carrier-free radioiodide by three methods (pH range 2.2--9.3), and with carrier-free radiobromide by the chloroperoxidase method (pH range 2.2--4.6). Albumin was also indirectly halogenated by attaching a radioiodinated acylating agent, N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP). The labeled proteins were proteolyzed enzymatically at neutral pH and the labeled amino acids produced were analyzed by liquid chromatography. Iodination at pH 7 yielded predominantly monoiodotyrosine, but at lower pH, fewer tyrosyl residues are labeled and a greater number of unstable sulfur-iodine bonds are formed at cysteinyl residues. Bromination with chloroperoxidase resulted in a high degree of labeling of cysteinyl residues at pH 2.8, the condition for optimum activity of this halogenating enzyme. Indirect halogenation with SHPP resulted in labeling of mid-chain lysyl, histidyl and tyrosyl residues.", "contents": "Sites of direct and indirect halogenation of albumin. The sites of radiohalogenation in proteins vary with the labeling method and the pH of the labeling reaciton. We have directly halogenated albumin with carrier-free radioiodide by three methods (pH range 2.2--9.3), and with carrier-free radiobromide by the chloroperoxidase method (pH range 2.2--4.6). Albumin was also indirectly halogenated by attaching a radioiodinated acylating agent, N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP). The labeled proteins were proteolyzed enzymatically at neutral pH and the labeled amino acids produced were analyzed by liquid chromatography. Iodination at pH 7 yielded predominantly monoiodotyrosine, but at lower pH, fewer tyrosyl residues are labeled and a greater number of unstable sulfur-iodine bonds are formed at cysteinyl residues. Bromination with chloroperoxidase resulted in a high degree of labeling of cysteinyl residues at pH 2.8, the condition for optimum activity of this halogenating enzyme. Indirect halogenation with SHPP resulted in labeling of mid-chain lysyl, histidyl and tyrosyl residues."}
{"id": "PMID:27227", "title": "Characteristics and conversion of high molecular weight forms of renin in plasma and their incomplete activation by the current acid treatment.", "content": "Two distinctly different high molecular weight forms of renin are present in mouse plasma in addition to the well-recognized active 40 000 dalton form. The biggest form has a molecular weight of about 800 000, and is stable in 4 M urea, but can be converted to the active 40 000 dalton form, by storage, exposure to acid and limited proteolysis. The 70 000 dalton form can be activated by acid and limited proteolysis. However, the 70 000 dalton form does not change molecular weight with activation. By measuring renin, not only by its enzymatic activity, but also by the direct radioimmunoassay for the renin molecule, which measures enzymatically active as well as inactive renin, it was found that both forms were activated but neither of them completely. The validity of the currently used term \"total\" renin as the enzymatic renin activity after acid activation, is, therefore, questionable. The quantitative significance of this must await methods which can ensure complete conversion or activation of the high molecular weight forms of renin in plasma.", "contents": "Characteristics and conversion of high molecular weight forms of renin in plasma and their incomplete activation by the current acid treatment. Two distinctly different high molecular weight forms of renin are present in mouse plasma in addition to the well-recognized active 40 000 dalton form. The biggest form has a molecular weight of about 800 000, and is stable in 4 M urea, but can be converted to the active 40 000 dalton form, by storage, exposure to acid and limited proteolysis. The 70 000 dalton form can be activated by acid and limited proteolysis. However, the 70 000 dalton form does not change molecular weight with activation. By measuring renin, not only by its enzymatic activity, but also by the direct radioimmunoassay for the renin molecule, which measures enzymatically active as well as inactive renin, it was found that both forms were activated but neither of them completely. The validity of the currently used term \"total\" renin as the enzymatic renin activity after acid activation, is, therefore, questionable. The quantitative significance of this must await methods which can ensure complete conversion or activation of the high molecular weight forms of renin in plasma."}
{"id": "PMID:27228", "title": "Effect of pH on bovine liver catalase as determined by electron paramagnetic resonance.", "content": "Two major rhombic high-spin ferric heme signals are observed during the pH titration of bovine liver catalase. The less rhombic signal if dominant above pH 6.0 and the more rhombic signal below pH 6.0. Ethanol in high concentration enhances the relative intensity of the less rhombic signal. These data demonstrate the sensitivitiy of the ligand field to changes in catalase solvent and, furthermore, suggest that both rhombic configuration posses identical spectral and catalytic properties.", "contents": "Effect of pH on bovine liver catalase as determined by electron paramagnetic resonance. Two major rhombic high-spin ferric heme signals are observed during the pH titration of bovine liver catalase. The less rhombic signal if dominant above pH 6.0 and the more rhombic signal below pH 6.0. Ethanol in high concentration enhances the relative intensity of the less rhombic signal. These data demonstrate the sensitivitiy of the ligand field to changes in catalase solvent and, furthermore, suggest that both rhombic configuration posses identical spectral and catalytic properties."}
{"id": "PMID:27229", "title": "Studies on erythrocruorin. VII. Reconstitution of earthworm erythrocruorin from the apoprotein.", "content": "Apoerythrocruorin prepared from the giant respiratory hemoprotein of the earthworm (60 S, Mr = 3 X 10(-6)) is an electrophoretically homogeneous molecule which sediments as a single peak of low molecular weight (3.5 S) and has a lower alpha-helical content (approx. 30%) than the native protein. Titration of globin with ferric heme indicates the presence of different binding sites; however, after purification by ion exchange chromatography, the reconstitution product contains 1 haem/23 000 g of protein as the native molecule. Reconstituted ferric erythrocruorin is a low molecular weight hemichrome with the same optical and physicochemical properties of the hemichrome formed by natural ferric erythrocruorin. Reconstituted ferrous erythrocruorin reacquires the alpha-helical content and the quaternary structure of the native molecule. Reassociation into 10-S speices (1/12 of the whole molecules) is fast and easy, while that into whole molecules is slow and somewhat erratic. The functional properties of reconstituted ferrous erythrocruorin (oxygen affinity, cooperativity in oxygen binding, magnitude of Bohr effect) are very similar to those of the \"stable\" low cooperativity form of the undissociated protein.", "contents": "Studies on erythrocruorin. VII. Reconstitution of earthworm erythrocruorin from the apoprotein. Apoerythrocruorin prepared from the giant respiratory hemoprotein of the earthworm (60 S, Mr = 3 X 10(-6)) is an electrophoretically homogeneous molecule which sediments as a single peak of low molecular weight (3.5 S) and has a lower alpha-helical content (approx. 30%) than the native protein. Titration of globin with ferric heme indicates the presence of different binding sites; however, after purification by ion exchange chromatography, the reconstitution product contains 1 haem/23 000 g of protein as the native molecule. Reconstituted ferric erythrocruorin is a low molecular weight hemichrome with the same optical and physicochemical properties of the hemichrome formed by natural ferric erythrocruorin. Reconstituted ferrous erythrocruorin reacquires the alpha-helical content and the quaternary structure of the native molecule. Reassociation into 10-S speices (1/12 of the whole molecules) is fast and easy, while that into whole molecules is slow and somewhat erratic. The functional properties of reconstituted ferrous erythrocruorin (oxygen affinity, cooperativity in oxygen binding, magnitude of Bohr effect) are very similar to those of the \"stable\" low cooperativity form of the undissociated protein."}
{"id": "PMID:27230", "title": "Oxygen equilibrium analyses of isolated hemoglobins A2, Lepore-Washington and P-nilotic.", "content": "Oxygen equilibrium studies have been carried out on hemoglobins A2 (alpha2delta2), Lepore-Washington (alpha2(deltabeta)2) and P-Nilotic (alpha2(beta2delta)2) using the beta chain containing hemoglobins A and S as controls. This investigation was initiated mainly because of controversial data that have been published on the oxygen affinity of hemoglobin (Hb) A2 and because samples containing the rare Hb P-Nilotic became available. Each hemoglobin was isolated in pure form by anion  exchange chromatography; the samples used in the equilibrium analyses contained 100 mg Hb/dl with less than 5% ferrihemoglobin and no 2,3--diphosphoglycerate. Oxygen equilibrium analyses were made at 37 degrees C with the method of Benesch et al. (1965) Anal. Biochem. 11, 81--87; Anal. Biochem. 55, 245--248 (1973). A slight, but definite increase in oxygen affinity was observed for Hb A2 as well as for Hb P-Nilotic while the increase for the Hb Lepore-Washington was somewhat greater. The values for n, the Hill coefficient, and the Bohr effects were the same for all hemoglobin types. The differences in oxygen affinity of these hemoglobins apparently result from the differences in primary structure that are characteristic for those proteins.", "contents": "Oxygen equilibrium analyses of isolated hemoglobins A2, Lepore-Washington and P-nilotic. Oxygen equilibrium studies have been carried out on hemoglobins A2 (alpha2delta2), Lepore-Washington (alpha2(deltabeta)2) and P-Nilotic (alpha2(beta2delta)2) using the beta chain containing hemoglobins A and S as controls. This investigation was initiated mainly because of controversial data that have been published on the oxygen affinity of hemoglobin (Hb) A2 and because samples containing the rare Hb P-Nilotic became available. Each hemoglobin was isolated in pure form by anion  exchange chromatography; the samples used in the equilibrium analyses contained 100 mg Hb/dl with less than 5% ferrihemoglobin and no 2,3--diphosphoglycerate. Oxygen equilibrium analyses were made at 37 degrees C with the method of Benesch et al. (1965) Anal. Biochem. 11, 81--87; Anal. Biochem. 55, 245--248 (1973). A slight, but definite increase in oxygen affinity was observed for Hb A2 as well as for Hb P-Nilotic while the increase for the Hb Lepore-Washington was somewhat greater. The values for n, the Hill coefficient, and the Bohr effects were the same for all hemoglobin types. The differences in oxygen affinity of these hemoglobins apparently result from the differences in primary structure that are characteristic for those proteins."}
{"id": "PMID:27231", "title": "The cleavage and adsorption of parathyroid hormone at high dilution: implications for receptor binding studies.", "content": "Like other polypeptide hormones, purified intact parathyroid hormone (1-84)parathyroid hormone is notoriously unstable and is subject to large adsorptive losses in routine laboratory manipulation. The present studies were undertaken with 125I-labeled hormone to quantitate the problem and to develop preventative measures, particularly with concentrations of physiological interest, 1 . 10(-10) M. It was found that spontaneous cleavage of the hormone takes place upon its incubation in air or oxygen. This can be prevented by the presence of mercaptoethanol or by plasma levels of cysteine and ascorbate. Under non-cleavage conditions, adsorption was found to be extensive on all materials tested. This adsorption increased with time up to 2 h, was independent of ionic strength, increased with increasing temperature and was presumed to involve hydrophobic interactions. Under given conditions, adsorption was proportional to concentration (constant percentage). However, at very high concentrations, 1 . 10(-6) M, adsorption was markedly reduced. Adsorption was minimized at low pH (2). Bovine serum albumin reduced adsorption under all conditions when present at concentrations of 2 mg/ml or more. Coating laboratory ware with cetyl alcohol also was helpful. Using optimal conditions, cleavage is prevented and losses are less than 5% at neutral pH, and under 2% at pH 2.", "contents": "The cleavage and adsorption of parathyroid hormone at high dilution: implications for receptor binding studies. Like other polypeptide hormones, purified intact parathyroid hormone (1-84)parathyroid hormone is notoriously unstable and is subject to large adsorptive losses in routine laboratory manipulation. The present studies were undertaken with 125I-labeled hormone to quantitate the problem and to develop preventative measures, particularly with concentrations of physiological interest, 1 . 10(-10) M. It was found that spontaneous cleavage of the hormone takes place upon its incubation in air or oxygen. This can be prevented by the presence of mercaptoethanol or by plasma levels of cysteine and ascorbate. Under non-cleavage conditions, adsorption was found to be extensive on all materials tested. This adsorption increased with time up to 2 h, was independent of ionic strength, increased with increasing temperature and was presumed to involve hydrophobic interactions. Under given conditions, adsorption was proportional to concentration (constant percentage). However, at very high concentrations, 1 . 10(-6) M, adsorption was markedly reduced. Adsorption was minimized at low pH (2). Bovine serum albumin reduced adsorption under all conditions when present at concentrations of 2 mg/ml or more. Coating laboratory ware with cetyl alcohol also was helpful. Using optimal conditions, cleavage is prevented and losses are less than 5% at neutral pH, and under 2% at pH 2."}
{"id": "PMID:27232", "title": "An evaluation of respiration chain-associated functions during initiation of germination of Bacillus megaterium spores.", "content": "In Bacillus megaterium QM B1551, spore germination could be initiated by glucose in the absence of detectable oxygen consumption, ATP synthesis or a pH decrease in the external media, suggesting that none of those reactions were mandatory. In addition, initiation of germination was insensitive to a variety of inhibitors of energy production or protonmotive force uncouplers. Therefore the respiratory chain-associated functions are not prerequisites for initiation of germination but these functions may be necessary to drive energy-dependent transport systems and other biosynthetic reactions during outgrowth.", "contents": "An evaluation of respiration chain-associated functions during initiation of germination of Bacillus megaterium spores. In Bacillus megaterium QM B1551, spore germination could be initiated by glucose in the absence of detectable oxygen consumption, ATP synthesis or a pH decrease in the external media, suggesting that none of those reactions were mandatory. In addition, initiation of germination was insensitive to a variety of inhibitors of energy production or protonmotive force uncouplers. Therefore the respiratory chain-associated functions are not prerequisites for initiation of germination but these functions may be necessary to drive energy-dependent transport systems and other biosynthetic reactions during outgrowth."}
{"id": "PMID:27233", "title": "Mediated transport and metabolism of lactate in rat aorta.", "content": "1. Under appropriate conditions L- and D-lactate enter the cells of rat aorta and are metabolized. Oxidation of lactate to CO2 occurs under aerobic conditions. 2. L- and D-lactate are taken up into the cells when oxygen, glucose, or both oxygen and glucose are present in the incubation medium. Both L- and D-lactate are excluded from the cells when neither oxygen nor glucose is present. 3. D,L-Glyceraldehyde prevents the uptake of L-lactate. The effect is apparently not due to the inhibition of glucose metabolism by L-glyceraldehyde. 4. L-lactate (20 mM) markedly inhibits the uptake of 5 mM D-lactate, but 20 mM D-lactate fails to inhibit the uptake of 5 mM L-lactate. 5. Raising the pH of the incubation medium markedly depresses the uptake of L-lactate. 6. The results provide evidence that L- and D-lactate enter the cells of rat aorta by a mediated transport system.", "contents": "Mediated transport and metabolism of lactate in rat aorta. 1. Under appropriate conditions L- and D-lactate enter the cells of rat aorta and are metabolized. Oxidation of lactate to CO2 occurs under aerobic conditions. 2. L- and D-lactate are taken up into the cells when oxygen, glucose, or both oxygen and glucose are present in the incubation medium. Both L- and D-lactate are excluded from the cells when neither oxygen nor glucose is present. 3. D,L-Glyceraldehyde prevents the uptake of L-lactate. The effect is apparently not due to the inhibition of glucose metabolism by L-glyceraldehyde. 4. L-lactate (20 mM) markedly inhibits the uptake of 5 mM D-lactate, but 20 mM D-lactate fails to inhibit the uptake of 5 mM L-lactate. 5. Raising the pH of the incubation medium markedly depresses the uptake of L-lactate. 6. The results provide evidence that L- and D-lactate enter the cells of rat aorta by a mediated transport system."}
{"id": "PMID:27234", "title": "Changes in collagen cross-linking and lysyl oxidase by estrogen.", "content": "Dermal collagen solubility and lysyl oxidase activity of bones were measured in DDD mice of advancing age. Insoluble fractions of the dermal collagen increased more rapidly in females than in males after 5 weeks of age. Activity of the lysyl oxidase extracted from bones was higher in females than in males after 4 weeks of age. After sexual maturation, such sex differences were always observed in skin as well as in bone tissue. In other experimental animals, dermal collagen solubility was markedly decreased by estrogen treatment and lysyl oxidase was remarkably activated by estrogen in both skin and bone. Thus it is clear that estrogen stimulates the enzyme activity and accelerates the maturation of collagen and elastin in extracellular space.", "contents": "Changes in collagen cross-linking and lysyl oxidase by estrogen. Dermal collagen solubility and lysyl oxidase activity of bones were measured in DDD mice of advancing age. Insoluble fractions of the dermal collagen increased more rapidly in females than in males after 5 weeks of age. Activity of the lysyl oxidase extracted from bones was higher in females than in males after 4 weeks of age. After sexual maturation, such sex differences were always observed in skin as well as in bone tissue. In other experimental animals, dermal collagen solubility was markedly decreased by estrogen treatment and lysyl oxidase was remarkably activated by estrogen in both skin and bone. Thus it is clear that estrogen stimulates the enzyme activity and accelerates the maturation of collagen and elastin in extracellular space."}
{"id": "PMID:27235", "title": "Effects of catecholamines and glucagon on glycogen metabolism in human polymorphonuclear leukocytes.", "content": "Addition of 10 micron of the alpha-adrenergic agonist phenylephrine to polymorphonuclear leukocytes suspended in glucose-free Krebs-Ringer bicarbonate buffer (pH 6.7) activated phosphorylase, inactivated glycogen synthase R maximally within 30 s, and resulted in glycogen breakdown. Phenylephrine increased 45Ca efflux relative to control of 45Ca prelabelled cells, but did not affect cyclic adenosine 3',5'-monophosphate (cAMP) concentration. The effects of phenylephrine were blocked by 20 micron phentolamine and were absent in cells incubated at pH 7.4. The same unexplained dependency of extracellular pH was observed with 2.5 nM--2.5 micron glucagon, which activated phosphorylase and inactivated synthase-R, but in addition caused a 30-s burst in cAMP formation. 25 nM glucagon also increased 45Ca efflux. The activation of phosphorylase by phenylephrine and possibly also by glucagon are thought mediated by an increased concentration of cytosolic Ca2+ activating phosphorylase kinase. The effects of 5 micron isoproterenol or 5 micron epinephrine were independent of extracellular pH 6.7 and 7.4 and resulted in a sustained increase in cAMP, an activation of phosphorylase and inactivation of synthase-R within 15 s, and in glycogenolysis. The effects of both compounds were blocked by 10 micron propranolol, whereas 10 micron phentolamine had no effect on the epinephrine action. The efflux of 45Ca was not affected by either isoproterenol or epinephrine. The beta-adrenergic activation of phosphorylase is consistent with the assumption of a covalent modification of phosphorylase kinase by the cAMP dependent protein kinase. Phosphorylation of synthase-R to synthase-D can thus occur independently of increase in cAMP, but the evidence is inconclusive with respect to the cAMP dependent protein kinase also being active in this phosphorylation.", "contents": "Effects of catecholamines and glucagon on glycogen metabolism in human polymorphonuclear leukocytes. Addition of 10 micron of the alpha-adrenergic agonist phenylephrine to polymorphonuclear leukocytes suspended in glucose-free Krebs-Ringer bicarbonate buffer (pH 6.7) activated phosphorylase, inactivated glycogen synthase R maximally within 30 s, and resulted in glycogen breakdown. Phenylephrine increased 45Ca efflux relative to control of 45Ca prelabelled cells, but did not affect cyclic adenosine 3',5'-monophosphate (cAMP) concentration. The effects of phenylephrine were blocked by 20 micron phentolamine and were absent in cells incubated at pH 7.4. The same unexplained dependency of extracellular pH was observed with 2.5 nM--2.5 micron glucagon, which activated phosphorylase and inactivated synthase-R, but in addition caused a 30-s burst in cAMP formation. 25 nM glucagon also increased 45Ca efflux. The activation of phosphorylase by phenylephrine and possibly also by glucagon are thought mediated by an increased concentration of cytosolic Ca2+ activating phosphorylase kinase. The effects of 5 micron isoproterenol or 5 micron epinephrine were independent of extracellular pH 6.7 and 7.4 and resulted in a sustained increase in cAMP, an activation of phosphorylase and inactivation of synthase-R within 15 s, and in glycogenolysis. The effects of both compounds were blocked by 10 micron propranolol, whereas 10 micron phentolamine had no effect on the epinephrine action. The efflux of 45Ca was not affected by either isoproterenol or epinephrine. The beta-adrenergic activation of phosphorylase is consistent with the assumption of a covalent modification of phosphorylase kinase by the cAMP dependent protein kinase. Phosphorylation of synthase-R to synthase-D can thus occur independently of increase in cAMP, but the evidence is inconclusive with respect to the cAMP dependent protein kinase also being active in this phosphorylation."}
{"id": "PMID:27236", "title": "Properties and partial purification of the detergent-solubilized insulin receptor: a demonstration of negative cooperativity in micellar solution.", "content": "Turkey erythrocytes possess insulin receptors with binding properties very similar to those of mammalian insulin receptors. In the present study, the insulin receptor of the avian erythrocyte has been solubilized in Triton X-100, extensively characterized and partially purified, and its properties compared to those of the membrane-bound receptor. The solubilized insulin receptor has a Stokes radius of 70 A and an apparent molecular weight of 300 000 in 0.05% Triton. The binding of insulin to the soluble receptor was very similar to the binding observed with the membrane-bound receptor. Thus, binding was markedly temperature dependent for both the soluble and membrane-bound forms, although the kinetics of binding were slower with the soluble receptor. Both forms of the receptor also showed a sharp pH optimum; however, solubilization produced a shift from maximal binding at pH 7.8 to pH 7.3. The soluble receptor also retained insulin analog specificity, ion sensitivity and negative cooperativity. The soluble receptor did not appear to degrade either bound or free insulin. On DEAE-cellulose chromatography the receptor eluted as a single peak. The specific activity of this partially purified preparation was 25--30 pmol/mg protein (about 500-fold enrichment over crude extract and 5-fold over highly purified membranes). Extensive attempts to purify further the receptor by gel filtration, carboxymethyl-cellulose chromatography and affinity chromatography resulted in either a very low yield or only modest enrichment. Purification was also complicated because the receptor was easily denatured; about 40% of the activity was lost after a 90-min exposure to 3 M urea or pH 4.5. These data suggest that the insulin receptor retains its properties in the absence of the lipid bilayer of the membrane. Complete purification will be difficult due to a lack of stability under a number of conditions.", "contents": "Properties and partial purification of the detergent-solubilized insulin receptor: a demonstration of negative cooperativity in micellar solution. Turkey erythrocytes possess insulin receptors with binding properties very similar to those of mammalian insulin receptors. In the present study, the insulin receptor of the avian erythrocyte has been solubilized in Triton X-100, extensively characterized and partially purified, and its properties compared to those of the membrane-bound receptor. The solubilized insulin receptor has a Stokes radius of 70 A and an apparent molecular weight of 300 000 in 0.05% Triton. The binding of insulin to the soluble receptor was very similar to the binding observed with the membrane-bound receptor. Thus, binding was markedly temperature dependent for both the soluble and membrane-bound forms, although the kinetics of binding were slower with the soluble receptor. Both forms of the receptor also showed a sharp pH optimum; however, solubilization produced a shift from maximal binding at pH 7.8 to pH 7.3. The soluble receptor also retained insulin analog specificity, ion sensitivity and negative cooperativity. The soluble receptor did not appear to degrade either bound or free insulin. On DEAE-cellulose chromatography the receptor eluted as a single peak. The specific activity of this partially purified preparation was 25--30 pmol/mg protein (about 500-fold enrichment over crude extract and 5-fold over highly purified membranes). Extensive attempts to purify further the receptor by gel filtration, carboxymethyl-cellulose chromatography and affinity chromatography resulted in either a very low yield or only modest enrichment. Purification was also complicated because the receptor was easily denatured; about 40% of the activity was lost after a 90-min exposure to 3 M urea or pH 4.5. These data suggest that the insulin receptor retains its properties in the absence of the lipid bilayer of the membrane. Complete purification will be difficult due to a lack of stability under a number of conditions."}
{"id": "PMID:27241", "title": "Properties of partially purified bovine brain dopamine beta-hydroxylase.", "content": "Dopamine beta-hydroxylase has been partially purified from bovine brain. A 140-fold purification factor was achieved using solubilization with Triton X-100, ammonium sulphate fractionation between 20-50 per cent saturation, affinity chromatography on concanavalin A-Sepharose 4 B and then filtration through Sephadex G200. The specific activity at the end was 51 nmoles/h/mg protein. The majority of endogenous inhibitors were lost. Immunological studies, kinetic studies, studies on the interaction with lectins and the effect of carboxylic acids on enzyme activity were carried out. Our data are in favour of the close similarity between the bovine brain and adrenal enzymes. No major differences could be found, at least with the characterization experiments using in the present study.", "contents": "Properties of partially purified bovine brain dopamine beta-hydroxylase. Dopamine beta-hydroxylase has been partially purified from bovine brain. A 140-fold purification factor was achieved using solubilization with Triton X-100, ammonium sulphate fractionation between 20-50 per cent saturation, affinity chromatography on concanavalin A-Sepharose 4 B and then filtration through Sephadex G200. The specific activity at the end was 51 nmoles/h/mg protein. The majority of endogenous inhibitors were lost. Immunological studies, kinetic studies, studies on the interaction with lectins and the effect of carboxylic acids on enzyme activity were carried out. Our data are in favour of the close similarity between the bovine brain and adrenal enzymes. No major differences could be found, at least with the characterization experiments using in the present study."}
{"id": "PMID:27238", "title": "[Effect of pH on the permeability and mechanical properties of intercellular contacts in the small intestinal epithelium].", "content": "It is shown that acid site population controlling ion permeation through cell contacts is localized in the region of tight junction. The isoelectric point of cell surface in the region to tight junction changed from mean pH = 2.37 +/- 0.1 for duodenum to pH =2.80 +/-  +/- 0.1 for ileum. The maximum of cell adhesion in the tissue reached at mean pH that corresponding the isoelectric point. It seems possible, that this acid site population take part in interaction of plasma membranes of neighbouring cells.", "contents": "[Effect of pH on the permeability and mechanical properties of intercellular contacts in the small intestinal epithelium]. It is shown that acid site population controlling ion permeation through cell contacts is localized in the region of tight junction. The isoelectric point of cell surface in the region to tight junction changed from mean pH = 2.37 +/- 0.1 for duodenum to pH =2.80 +/-  +/- 0.1 for ileum. The maximum of cell adhesion in the tissue reached at mean pH that corresponding the isoelectric point. It seems possible, that this acid site population take part in interaction of plasma membranes of neighbouring cells."}
{"id": "PMID:27242", "title": "New trends in cryoenzymology: I.-Supercooled aqueous solutions.", "content": "A water in oil emulsion technique is proposed to investigate enzyme catalyzed reactions at sub-zero temperatures in the supercooled liquid state to avoid some reversible effects of the usual cosolvents on kinetics. Some results are listed: potentialities and technical problems of the procedure are discussed.", "contents": "New trends in cryoenzymology: I.-Supercooled aqueous solutions. A water in oil emulsion technique is proposed to investigate enzyme catalyzed reactions at sub-zero temperatures in the supercooled liquid state to avoid some reversible effects of the usual cosolvents on kinetics. Some results are listed: potentialities and technical problems of the procedure are discussed."}
{"id": "PMID:27239", "title": "[Phosphorylation in acid shocked chloroplasts].", "content": "ADP phosphorylation up to 2.5 nmol per mg of chlorphyll has been found in chloroplasts from Vicia faba plants when the suspension was sharply acidified from pH 8 to pH 1.6 with excess of HC1/KC1 solution. This fact appears to be due to confromation relaxation of the coupling factor under acid-induced denaturation. Heat pretreatment inhibits this effect.", "contents": "[Phosphorylation in acid shocked chloroplasts]. ADP phosphorylation up to 2.5 nmol per mg of chlorphyll has been found in chloroplasts from Vicia faba plants when the suspension was sharply acidified from pH 8 to pH 1.6 with excess of HC1/KC1 solution. This fact appears to be due to confromation relaxation of the coupling factor under acid-induced denaturation. Heat pretreatment inhibits this effect."}
{"id": "PMID:27244", "title": "Capacity for biosynthesis of prostaglandin-related compounds: distribution and properties of the rate-limiting enzyme in hydrocorals, gorgoniants, and other coelenterates of the Caribbean and Pacific.", "content": "A convenient and reliable assay is described for PGEP synthetase, the rate-limiting enzyme determining the total capacity for biosynthesis of prostaglandin-related compounds. Results of such assays, performed withe fresh specimens under both field and laboratory conditions, newly identify several marine coelenterate species as potentially important resources of PGRCs for research and possible development. Properties of the typical marine coelenterate PGEP synthetase, and the reaction which this enzyme catalyzes, have been further characterized.", "contents": "Capacity for biosynthesis of prostaglandin-related compounds: distribution and properties of the rate-limiting enzyme in hydrocorals, gorgoniants, and other coelenterates of the Caribbean and Pacific. A convenient and reliable assay is described for PGEP synthetase, the rate-limiting enzyme determining the total capacity for biosynthesis of prostaglandin-related compounds. Results of such assays, performed withe fresh specimens under both field and laboratory conditions, newly identify several marine coelenterate species as potentially important resources of PGRCs for research and possible development. Properties of the typical marine coelenterate PGEP synthetase, and the reaction which this enzyme catalyzes, have been further characterized."}
{"id": "PMID:27245", "title": "[Kinetics and mechanism of nucleophilic effect on the oxidation of o-dianisidine catalyzed by horseradish peroxidase].", "content": "The effects of benzimidazole and 4-nitroimidazole on the reaction of o-dianisidine peroxidase oxidation within the pH range of 3.7--9.0 were studied. Both substituted imidazoles activate the reaction at less than 0.6. In the presence of 4-nitroimidazole the activation is non-competitive, whereas in the presence of benzimidazole it is of a mixed type, which is close to the non-competitive one. The kinetic parameters (kAcat, alpha, KA) for the reaction activated by both imidazoles were determined. It was assumed that the activators interact with the protein group (pK approximately to 6.5), which limits the enzyme activity. This results in the increase of pKapp of the protein group in question, resulting in the appearance of the maximal peroxidase activity in the alkaline region of pH. It was shown that the intermolecular interactions involved in the peroxidase-induced oxidative catalysis are largely due to electrostatic rather than to hydrophobic factors.", "contents": "[Kinetics and mechanism of nucleophilic effect on the oxidation of o-dianisidine catalyzed by horseradish peroxidase]. The effects of benzimidazole and 4-nitroimidazole on the reaction of o-dianisidine peroxidase oxidation within the pH range of 3.7--9.0 were studied. Both substituted imidazoles activate the reaction at less than 0.6. In the presence of 4-nitroimidazole the activation is non-competitive, whereas in the presence of benzimidazole it is of a mixed type, which is close to the non-competitive one. The kinetic parameters (kAcat, alpha, KA) for the reaction activated by both imidazoles were determined. It was assumed that the activators interact with the protein group (pK approximately to 6.5), which limits the enzyme activity. This results in the increase of pKapp of the protein group in question, resulting in the appearance of the maximal peroxidase activity in the alkaline region of pH. It was shown that the intermolecular interactions involved in the peroxidase-induced oxidative catalysis are largely due to electrostatic rather than to hydrophobic factors."}
{"id": "PMID:27246", "title": "[Properties of cyclic nucleotide phosphodiesterase from lingual taste papillae].", "content": "Phosphodiesterase activity is estimated in extracts and partially purified preparations from functionally different parts of bovine tongue. The enzyme activity varied from 4.0 to 10.4 nmole/mg of protein/min. Properties of phosphodiesterase from circumvallate papillae are studied, the pH optimum being 8.0--8.5, Km for cAMP--1.5.10(-4) M and for cGMP--6.5.10(-5) M. The enzyme activity did not change after the treatment with trypsin, protamine sulphate (0.01--1.0%), heparin (0.01--1.0) and taste agents: L-leucine (from 1.10(-2) M to 1.10(-5) M), quinine (from 4.10(-3) M to 4.10(-8) M) and D-glucose (from 1.10(-1) M to 1.10(-4) M). The protein inhibitor of the enzyme, isolated from retina external rod-cell segments considerably suppressed phosphodiesterase activity, and the protein activator from brain tissue stimulated it insignificantly. Thermostable protein modulators, which inhibit or activate (depending on experimental conditions) phosphodiesterase activity, are isolated from circumvallate papillae.", "contents": "[Properties of cyclic nucleotide phosphodiesterase from lingual taste papillae]. Phosphodiesterase activity is estimated in extracts and partially purified preparations from functionally different parts of bovine tongue. The enzyme activity varied from 4.0 to 10.4 nmole/mg of protein/min. Properties of phosphodiesterase from circumvallate papillae are studied, the pH optimum being 8.0--8.5, Km for cAMP--1.5.10(-4) M and for cGMP--6.5.10(-5) M. The enzyme activity did not change after the treatment with trypsin, protamine sulphate (0.01--1.0%), heparin (0.01--1.0) and taste agents: L-leucine (from 1.10(-2) M to 1.10(-5) M), quinine (from 4.10(-3) M to 4.10(-8) M) and D-glucose (from 1.10(-1) M to 1.10(-4) M). The protein inhibitor of the enzyme, isolated from retina external rod-cell segments considerably suppressed phosphodiesterase activity, and the protein activator from brain tissue stimulated it insignificantly. Thermostable protein modulators, which inhibit or activate (depending on experimental conditions) phosphodiesterase activity, are isolated from circumvallate papillae."}
{"id": "PMID:27247", "title": "[Coenzyme-induced slow transitions of NADP-sorbitol dehydrogenase from Gluconobacter oxydans].", "content": "The kinetic properties of NADP-dependent sorbitol dehydrogenase from G. oxydans cell extract were studied at pH 8.8 and 9.3 in the direction of D-sorbitol oxydation. It was shown that the shape of the kinetic curves of NADPH accumulation in time is characterised by initial burst whose magnitude depends on the concentration of the enzyme extract used. Preincubation of the enzyme with NADP or D-sorbitol eliminated the initial burst on these curves and transformed them into straight lines coming from the start of co-ordinates. The dependence of the stationary reaction rate on the enzyme extract concentration is not a linear one. The kinetic dependences of stationary rate of the reaction catalysed by the enzyme on the concentration of D-sorbitol and NADP at pH 8.8 and 9.3 were examined under all conditions studied; the shape of these kinetic curves altered to considerable extent with the alteration of the enzyme extract concentration in the reaction mixture and pH. At pH 9.3 several intermiediate plateaux were found on the curves of the D-sorbitol concentration dependent stationary rate of the reaction. The preincubation of the enzyme extract with NADP during 1.5 h removed the intermediate plateau on these curves and made them hyperbolic. Disk-electrophoresis of the enzyme extract in PAAG concentration gradient showed that at pH 8.8 the enzyme exists in one active form, while at pH 9.3 it exists in three major and three minor active forms of the enzyme differing in their molecular weights are found. It is assumed that the enzyme from G. oxydans cell extract can exist in a great number of molecular equilibrium forms, the rate of quilibrium being comparable or significantly less than that of the enzymatic reaction. NADP significantly influences on the equilibrium of the molecular forms of the enzyme.", "contents": "[Coenzyme-induced slow transitions of NADP-sorbitol dehydrogenase from Gluconobacter oxydans]. The kinetic properties of NADP-dependent sorbitol dehydrogenase from G. oxydans cell extract were studied at pH 8.8 and 9.3 in the direction of D-sorbitol oxydation. It was shown that the shape of the kinetic curves of NADPH accumulation in time is characterised by initial burst whose magnitude depends on the concentration of the enzyme extract used. Preincubation of the enzyme with NADP or D-sorbitol eliminated the initial burst on these curves and transformed them into straight lines coming from the start of co-ordinates. The dependence of the stationary reaction rate on the enzyme extract concentration is not a linear one. The kinetic dependences of stationary rate of the reaction catalysed by the enzyme on the concentration of D-sorbitol and NADP at pH 8.8 and 9.3 were examined under all conditions studied; the shape of these kinetic curves altered to considerable extent with the alteration of the enzyme extract concentration in the reaction mixture and pH. At pH 9.3 several intermiediate plateaux were found on the curves of the D-sorbitol concentration dependent stationary rate of the reaction. The preincubation of the enzyme extract with NADP during 1.5 h removed the intermediate plateau on these curves and made them hyperbolic. Disk-electrophoresis of the enzyme extract in PAAG concentration gradient showed that at pH 8.8 the enzyme exists in one active form, while at pH 9.3 it exists in three major and three minor active forms of the enzyme differing in their molecular weights are found. It is assumed that the enzyme from G. oxydans cell extract can exist in a great number of molecular equilibrium forms, the rate of quilibrium being comparable or significantly less than that of the enzymatic reaction. NADP significantly influences on the equilibrium of the molecular forms of the enzyme."}
{"id": "PMID:27248", "title": "[Presence of SH-groups and histidine in the active site of Chlorella glutamine synthetase].", "content": "The presence of two cysteine residues per each six monomers comprising the oligomer of Chlorella glutamine synthetase (E.C.6.3.1.2) is demonstrated using homogenous enzyme preparation. p-Chloromercuribenzoate (p-CMB) is found to inhibit glutamine synthetase activity, the degree of inhibition depending on the inhibitor concentration. The following enzyme reactivation by dithiotreitol (10(-2) M) was observed only when the enzyme was inactivated with 10(-5) M p-CMB under 15 min. preincubation. Preincubation of the enzyme with 10(-4) M p-CMB for 45 min. did not result in its reactivation. Gel filtration of glutamine synthetase treated with 10(-4) M p-CMB has revealed the dissociation of the enzyme into inactive monomers. Incubation of glutamine synthetase with p-CMB at various pH values, incubation after pre-treatment with urea and experiments with HgCl2 indicate the presence of free and masked inside the globula SH-groups in the enzyme molecule. Competitive character of the enzyme inhibition with p-CMB with respect to ATP indicates that SH-groups of the active site participate in the ATP binding, probably, as Mg-ATP or Mn-ATP complexes. Data on the estimation of ionization constant of glutamate-binding group and experiments on the effect of histidine photooxidation on the enzyme activity indicate the presence of histidine residue in the enzyme active site, which participates in glutamate binding.", "contents": "[Presence of SH-groups and histidine in the active site of Chlorella glutamine synthetase]. The presence of two cysteine residues per each six monomers comprising the oligomer of Chlorella glutamine synthetase (E.C.6.3.1.2) is demonstrated using homogenous enzyme preparation. p-Chloromercuribenzoate (p-CMB) is found to inhibit glutamine synthetase activity, the degree of inhibition depending on the inhibitor concentration. The following enzyme reactivation by dithiotreitol (10(-2) M) was observed only when the enzyme was inactivated with 10(-5) M p-CMB under 15 min. preincubation. Preincubation of the enzyme with 10(-4) M p-CMB for 45 min. did not result in its reactivation. Gel filtration of glutamine synthetase treated with 10(-4) M p-CMB has revealed the dissociation of the enzyme into inactive monomers. Incubation of glutamine synthetase with p-CMB at various pH values, incubation after pre-treatment with urea and experiments with HgCl2 indicate the presence of free and masked inside the globula SH-groups in the enzyme molecule. Competitive character of the enzyme inhibition with p-CMB with respect to ATP indicates that SH-groups of the active site participate in the ATP binding, probably, as Mg-ATP or Mn-ATP complexes. Data on the estimation of ionization constant of glutamate-binding group and experiments on the effect of histidine photooxidation on the enzyme activity indicate the presence of histidine residue in the enzyme active site, which participates in glutamate binding."}
{"id": "PMID:27249", "title": "[Isolation, purification and characterization of regulatory properties of adenylate cyclase from rabbit heart].", "content": "Rabbit heart membranes possessing the adenylate cyclase activity were isolated and purified by extraction with high ionic strength solutions and centrifugation in the sucrose density gradient. It was shown that the membranes are characterized by a high percentage of cholesterol (molar ratio cholesterol/phospholipids is 0.24) and an increased activity of Na, K-ATPase, which suggests the localization of adenylate cyclase in the sarcolemma. During centrifugation in the sucrose density gradient the activities of andenylate cyclase and Na,K-ATPase are not separated. Treatment of heart sarcolemma with a 0.3% solution of lubrol WX results in 10--20% solubilization of adenylate cyclase. Purification of the enzyme in the membrane fraction is accompanied by a decrease in the activity of phosphodiesterase; however, about 2% of the heart diesterase total activity cannot be removed from the sarcolemma even after its treatment with 0.3% lubrol WX. Epinephrine and NaF activate adenylate cyclase without changing the pH dependence of the enzyme. The alpha-adrenergic antagonist phentolamine has no effect on the adenylate cyclase activation by catecholamines, glucagon and histamine; the beta-adrenergic antagonist alprenolol competitively inhibits the effects of isoproterenol, epinephrine and norepinephrine, having no effect on the enzyme activation by glucagon and histamine. There is no competition between epinephrine, glucagon and histamine for the binding site of the hormone; however, there may occur a competition between the hormone receptors for the binding to the enzyme. A combined action of several hormones on the membranes results in the averaging of their individual activating effects. When the hormones were added one after another, the extent of adenylate cyclase activation corresponded to that induced by the first hormone; the activation was insensitive to the effect of the second hormone added. It is assumed that the outer membrane of myocardium cells contains a adenylate cyclase and three types of receptors, each being capable to interact with the same form of enzyme. The activity of adenylate cyclase is determined by the type of the receptor, to which it is bound and by the amount of the enzyme-receptor complex.", "contents": "[Isolation, purification and characterization of regulatory properties of adenylate cyclase from rabbit heart]. Rabbit heart membranes possessing the adenylate cyclase activity were isolated and purified by extraction with high ionic strength solutions and centrifugation in the sucrose density gradient. It was shown that the membranes are characterized by a high percentage of cholesterol (molar ratio cholesterol/phospholipids is 0.24) and an increased activity of Na, K-ATPase, which suggests the localization of adenylate cyclase in the sarcolemma. During centrifugation in the sucrose density gradient the activities of andenylate cyclase and Na,K-ATPase are not separated. Treatment of heart sarcolemma with a 0.3% solution of lubrol WX results in 10--20% solubilization of adenylate cyclase. Purification of the enzyme in the membrane fraction is accompanied by a decrease in the activity of phosphodiesterase; however, about 2% of the heart diesterase total activity cannot be removed from the sarcolemma even after its treatment with 0.3% lubrol WX. Epinephrine and NaF activate adenylate cyclase without changing the pH dependence of the enzyme. The alpha-adrenergic antagonist phentolamine has no effect on the adenylate cyclase activation by catecholamines, glucagon and histamine; the beta-adrenergic antagonist alprenolol competitively inhibits the effects of isoproterenol, epinephrine and norepinephrine, having no effect on the enzyme activation by glucagon and histamine. There is no competition between epinephrine, glucagon and histamine for the binding site of the hormone; however, there may occur a competition between the hormone receptors for the binding to the enzyme. A combined action of several hormones on the membranes results in the averaging of their individual activating effects. When the hormones were added one after another, the extent of adenylate cyclase activation corresponded to that induced by the first hormone; the activation was insensitive to the effect of the second hormone added. It is assumed that the outer membrane of myocardium cells contains a adenylate cyclase and three types of receptors, each being capable to interact with the same form of enzyme. The activity of adenylate cyclase is determined by the type of the receptor, to which it is bound and by the amount of the enzyme-receptor complex."}
{"id": "PMID:27250", "title": "[Properties of DNA-methylase reaction in isolated nuclei of normal and regenerating rat liver].", "content": "Evidence from comparative determination of DNA radioactivity methylation degree of acidic extraction and chlorophormic deproteination of the samples suggest that the former technique is a more efficient one. The properties of the DNA-methylase reaction in isolated rat liver nuclei were studied. The DNA-methylase activity is found to be considerably stable during incubation of the nuclei at 37 degrees C; a broad pH-optimum in the alkaline region is observed (pH 8.6--9.8); this activity is inhibited by Mn2+, nucleotides, actynomycin and S-adenosyl methionine analogs and is activated by Mg2+; the incorporation of methyl groups into DNA is reversible. The data suggest that the DNA-methylase activities of the nuclei isolated at different stages of regeneration do not show substantial variations. No differences in DNA methylation before and after DNA synthesis in the regenerating nuclei were observed. Inhibition of DNA synthesis in the course of regeneration does not decrease the level of DNA methylation. The interrelationship between methylation and replication of DNA is discussed.", "contents": "[Properties of DNA-methylase reaction in isolated nuclei of normal and regenerating rat liver]. Evidence from comparative determination of DNA radioactivity methylation degree of acidic extraction and chlorophormic deproteination of the samples suggest that the former technique is a more efficient one. The properties of the DNA-methylase reaction in isolated rat liver nuclei were studied. The DNA-methylase activity is found to be considerably stable during incubation of the nuclei at 37 degrees C; a broad pH-optimum in the alkaline region is observed (pH 8.6--9.8); this activity is inhibited by Mn2+, nucleotides, actynomycin and S-adenosyl methionine analogs and is activated by Mg2+; the incorporation of methyl groups into DNA is reversible. The data suggest that the DNA-methylase activities of the nuclei isolated at different stages of regeneration do not show substantial variations. No differences in DNA methylation before and after DNA synthesis in the regenerating nuclei were observed. Inhibition of DNA synthesis in the course of regeneration does not decrease the level of DNA methylation. The interrelationship between methylation and replication of DNA is discussed."}
{"id": "PMID:27251", "title": "[Effect of cortisol on the content of mRNA coding inducible tyrosine aminotransferase isoenzyme in rat liver].", "content": "In vitro estimation of synthesis of inducible tyrosine aminotransferase isoenzyme, directed by poly-A-containing RNA from liver of intact and corticol treated rats, is carried out. Total poly-A-containing RNA from liver polyribosomes of intact and induced rats was translated in cell-free system from wheat germs. Two antibodies immunoprecipitation was used to identify the translocation product (tyrosine aminotransferase). It was found that a synthesis of a specific protein product, precipitated by antibodies to tyrosine aminotransferase, takes place in cell-free system under translation of polysomic poly-A-containing liver RNA. The amount of immunoprecipitated product indicates, that the content of individual poly-A-containing mRNA for inducible tyrosine aminotransferase isoenzyme in liver of cortisol-induced rats is considerably higher than in intact animals.", "contents": "[Effect of cortisol on the content of mRNA coding inducible tyrosine aminotransferase isoenzyme in rat liver]. In vitro estimation of synthesis of inducible tyrosine aminotransferase isoenzyme, directed by poly-A-containing RNA from liver of intact and corticol treated rats, is carried out. Total poly-A-containing RNA from liver polyribosomes of intact and induced rats was translated in cell-free system from wheat germs. Two antibodies immunoprecipitation was used to identify the translocation product (tyrosine aminotransferase). It was found that a synthesis of a specific protein product, precipitated by antibodies to tyrosine aminotransferase, takes place in cell-free system under translation of polysomic poly-A-containing liver RNA. The amount of immunoprecipitated product indicates, that the content of individual poly-A-containing mRNA for inducible tyrosine aminotransferase isoenzyme in liver of cortisol-induced rats is considerably higher than in intact animals."}
{"id": "PMID:27252", "title": "Evaluating clustering methods for psychiatric diagnosis.", "content": "This report represents an empirical evaluation of the major clustering approaches on psychiatric diagnostic data. Experienced psychiatrists, using 17 psychopathological variables, developed 88 archetypal psychiatric patients to represent four diagnostic categories (manic-depressive depressed, manic-depressive manic, simple schizophrenic, and paranoid schizophrenic). Ten computerized methods representative of the major clustering approaches and using various measures of similarity between patients were applied to this data set to develop de novo patient groupings. Evaluative criteria included the concordance of clustering output to the structure of the original data, and clustering replicability. Considerable differences were obtained among clustering methods. The best-ranked procedures were nearest centroid sorting methods and complete and centroid linkage hierarchical methods. The overall poorest ranking were obtained for multivariate normal mixture analysis and facial representation of multidimensional points. Further evaluation of cluster analytic methods on real biological and psychosocial data sets yielded similar rankings.", "contents": "Evaluating clustering methods for psychiatric diagnosis. This report represents an empirical evaluation of the major clustering approaches on psychiatric diagnostic data. Experienced psychiatrists, using 17 psychopathological variables, developed 88 archetypal psychiatric patients to represent four diagnostic categories (manic-depressive depressed, manic-depressive manic, simple schizophrenic, and paranoid schizophrenic). Ten computerized methods representative of the major clustering approaches and using various measures of similarity between patients were applied to this data set to develop de novo patient groupings. Evaluative criteria included the concordance of clustering output to the structure of the original data, and clustering replicability. Considerable differences were obtained among clustering methods. The best-ranked procedures were nearest centroid sorting methods and complete and centroid linkage hierarchical methods. The overall poorest ranking were obtained for multivariate normal mixture analysis and facial representation of multidimensional points. Further evaluation of cluster analytic methods on real biological and psychosocial data sets yielded similar rankings."}
{"id": "PMID:27253", "title": "Difficulties in comparing catecholamine-related enzymes from the brains of schizophrenics and controls.", "content": "The catecholamine-forming and metabolizing enzyme tyrosine hydroxylase, dopa decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine N-methyltransferase, and catecholamine-O-methyltransferase, as well as the endogenous inhibitor of dopamine-beta-hydroxylase were compared in the brains of schizophrenics and controls. While there were no statistically significant differences in the enzyme or inhibitor activity between groups, tbre was a decided trend toward a decreased enzyme activity in the brains of the schizophrenics. From another set of control brains it was found that changes in human enzyme activity following death are variable and may be dependent on how the brains were handled. Thus, it is unclear whether the apparent differences between schizophrenics and controls were present when they were alive or occurred after death.", "contents": "Difficulties in comparing catecholamine-related enzymes from the brains of schizophrenics and controls. The catecholamine-forming and metabolizing enzyme tyrosine hydroxylase, dopa decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine N-methyltransferase, and catecholamine-O-methyltransferase, as well as the endogenous inhibitor of dopamine-beta-hydroxylase were compared in the brains of schizophrenics and controls. While there were no statistically significant differences in the enzyme or inhibitor activity between groups, tbre was a decided trend toward a decreased enzyme activity in the brains of the schizophrenics. From another set of control brains it was found that changes in human enzyme activity following death are variable and may be dependent on how the brains were handled. Thus, it is unclear whether the apparent differences between schizophrenics and controls were present when they were alive or occurred after death."}
{"id": "PMID:27258", "title": "Effect of anticonvulsant drugs on alkaline phosphatase and gamma-glutamyltransferase activity in human leukocytes.", "content": "The authors compared the alkaline phosphatase and gamma-glutamyl-transferase activities in leukocytes from presumably healthy subjects and from epileptic patients treated with anticonvulsants, matched for age and sex. Intraleukocyte alkaline phosphatase activity was higher in women than in men and was greatly reduced by the anticonvulsant drugs. Intraleukocyte gammaglutamyltransferase activity did not vary with sex and was unaffected by the anticonvulsant drugs contrary to findings for the activity of this enzyme in plasma and liver.", "contents": "Effect of anticonvulsant drugs on alkaline phosphatase and gamma-glutamyltransferase activity in human leukocytes. The authors compared the alkaline phosphatase and gamma-glutamyl-transferase activities in leukocytes from presumably healthy subjects and from epileptic patients treated with anticonvulsants, matched for age and sex. Intraleukocyte alkaline phosphatase activity was higher in women than in men and was greatly reduced by the anticonvulsant drugs. Intraleukocyte gammaglutamyltransferase activity did not vary with sex and was unaffected by the anticonvulsant drugs contrary to findings for the activity of this enzyme in plasma and liver."}
{"id": "PMID:27259", "title": "Thermodynamic investigations of proteins. IV. Calcium binding protein parvalbumin.", "content": "The conformational transitions of calcium binding protein parvalbumin III from carp muscle were studied by scanning calorimetry, potentiometric titration and isothermal calorimetric titration. Changes of Gibbs energy, enthalpy and partial heat capacity were determined. The removal of calcium ions by EDTA is accompanied by 1) a heat absorption of 75 +/- 10 kJ per mole of the protein, 2) a decrease in the Gibbs energy of protein structure stabilisation of about 42 kJ mol-1 and 3) a decrease in thermostability by more than 50 K. The protonation of the acidic groups leads to a loss of calcium followed by denaturation, while the pH of the transition strongly depends on calcium activity. The enthalpy and heat capacity changes at denaturation are comparable with the values observed for other compact globular proteins.", "contents": "Thermodynamic investigations of proteins. IV. Calcium binding protein parvalbumin. The conformational transitions of calcium binding protein parvalbumin III from carp muscle were studied by scanning calorimetry, potentiometric titration and isothermal calorimetric titration. Changes of Gibbs energy, enthalpy and partial heat capacity were determined. The removal of calcium ions by EDTA is accompanied by 1) a heat absorption of 75 +/- 10 kJ per mole of the protein, 2) a decrease in the Gibbs energy of protein structure stabilisation of about 42 kJ mol-1 and 3) a decrease in thermostability by more than 50 K. The protonation of the acidic groups leads to a loss of calcium followed by denaturation, while the pH of the transition strongly depends on calcium activity. The enthalpy and heat capacity changes at denaturation are comparable with the values observed for other compact globular proteins."}
{"id": "PMID:27256", "title": "Immunosuppressive activity of two plant steroidal lactones withaferin A and withanolide E.", "content": "Withaferin A and withanolide E, two steroidal lactones of plant origin were demonstrated to have specific immunosuppressive effects on human B and T lymphocytes as well as on mice thymocytes. E rosettes and EAC rosette formation by normal human T and B lymphocytes were inhibited by the two compounds at very low concentrations. The formation of mouse red blood rosettes by chronic lymphatic leukemic cells were only inhibited by withaferin A. The functional activity of normal human T lymphocytes as assessed by a local xenogeneic graft versus host reaction was also affected by these two plant steroidal lactones. These experiments demonstrate a specific action of the compound on antigen recognition as well as proliferative capacity of T lymphocytes as well as B lymphocytes.", "contents": "Immunosuppressive activity of two plant steroidal lactones withaferin A and withanolide E. Withaferin A and withanolide E, two steroidal lactones of plant origin were demonstrated to have specific immunosuppressive effects on human B and T lymphocytes as well as on mice thymocytes. E rosettes and EAC rosette formation by normal human T and B lymphocytes were inhibited by the two compounds at very low concentrations. The formation of mouse red blood rosettes by chronic lymphatic leukemic cells were only inhibited by withaferin A. The functional activity of normal human T lymphocytes as assessed by a local xenogeneic graft versus host reaction was also affected by these two plant steroidal lactones. These experiments demonstrate a specific action of the compound on antigen recognition as well as proliferative capacity of T lymphocytes as well as B lymphocytes."}
{"id": "PMID:27260", "title": "Temperature dependence of the interfacial behavior of uracil derivatives.", "content": "The effect of temperature on the interfacial behavior of uracil, thymine and 1,5-dimethyluracil has been used to characterize the thermodynamics of adsorption of these compounds at a mercury electrode-aqueous electrolyte interface. Between 4.5 degrees C and 40 degrees C all three compounds exhibit two adsorption regions. The first, a dilute layer where the molecules adsorb in a flat orientation on the electrode surface. The second, a compact layer where the molecules adsorb in a perpendicular orientation. The thermodynamic constants characterizing formation of these surface layers have been deduced.", "contents": "Temperature dependence of the interfacial behavior of uracil derivatives. The effect of temperature on the interfacial behavior of uracil, thymine and 1,5-dimethyluracil has been used to characterize the thermodynamics of adsorption of these compounds at a mercury electrode-aqueous electrolyte interface. Between 4.5 degrees C and 40 degrees C all three compounds exhibit two adsorption regions. The first, a dilute layer where the molecules adsorb in a flat orientation on the electrode surface. The second, a compact layer where the molecules adsorb in a perpendicular orientation. The thermodynamic constants characterizing formation of these surface layers have been deduced."}
{"id": "PMID:27257", "title": "Action of beta-adrenoceptor blocking agents on hemodynamic variables and on baroreceptor and postganglionic sympathetic activities in rabbits.", "content": "Fifty-six experiments were performed in rabbits anesthetized by urethane or sodium pentobarbital. Baroreceptor (aortic nerve) and post-ganglionic sympathetic (renal nerve) activities were recorded, and peripheral resistances were determined after infusion of beta-adrenoceptor blocking agents (propranolol, pindolol, timolol). A progressive vasodilation was observed after the onset of infusion of the 3 drugs; at the same time arterial pressure decreased, but aortic flow did not vary significantly. Baroreceptor activity was enhanced, whereas efferent renal nerve activity was decreased.", "contents": "Action of beta-adrenoceptor blocking agents on hemodynamic variables and on baroreceptor and postganglionic sympathetic activities in rabbits. Fifty-six experiments were performed in rabbits anesthetized by urethane or sodium pentobarbital. Baroreceptor (aortic nerve) and post-ganglionic sympathetic (renal nerve) activities were recorded, and peripheral resistances were determined after infusion of beta-adrenoceptor blocking agents (propranolol, pindolol, timolol). A progressive vasodilation was observed after the onset of infusion of the 3 drugs; at the same time arterial pressure decreased, but aortic flow did not vary significantly. Baroreceptor activity was enhanced, whereas efferent renal nerve activity was decreased."}
{"id": "PMID:27261", "title": "Volume changes during enzyme reactions. The influence of pressure on the action of invertase, dextranase and dextransucrase.", "content": "The pressure dependence of the maximum velocities and the Michaelis constants for the enzymes invertase and dextranase was measured up to 1400 bar. The corresponding activation volumes deltaV not equal to c and deltaV not equal to Km proved to be independent of pressure. Together with data from other sources the meaning of deltaV not equal to c and deltaV not equal to Km is established and the volume profiles of the reactions are constructed. These profiles are similar in contour to the volume profile of the dextran formation catalyzed by the enzyme dextransucrase, but the amount of the volume changes is very much larger for dextransucrase. The evaluation of salt effects shows, that for all three enzymes solvent interactions are not important in explaining the results. The reaction mechanisms seem to be governed by conformation changes of the enzymes. The larger effects in dextransucrase are explained by the produced dextran chain remaining tightly bound to the enzyme and being transported relative to the enzymes position in each reaction cycle.", "contents": "Volume changes during enzyme reactions. The influence of pressure on the action of invertase, dextranase and dextransucrase. The pressure dependence of the maximum velocities and the Michaelis constants for the enzymes invertase and dextranase was measured up to 1400 bar. The corresponding activation volumes deltaV not equal to c and deltaV not equal to Km proved to be independent of pressure. Together with data from other sources the meaning of deltaV not equal to c and deltaV not equal to Km is established and the volume profiles of the reactions are constructed. These profiles are similar in contour to the volume profile of the dextran formation catalyzed by the enzyme dextransucrase, but the amount of the volume changes is very much larger for dextransucrase. The evaluation of salt effects shows, that for all three enzymes solvent interactions are not important in explaining the results. The reaction mechanisms seem to be governed by conformation changes of the enzymes. The larger effects in dextransucrase are explained by the produced dextran chain remaining tightly bound to the enzyme and being transported relative to the enzymes position in each reaction cycle."}
{"id": "PMID:27262", "title": "[Effect of the alpha-adrenoblocker pyrroxan on systemic hemodynamics in puppies and dogs with vasorenal hypertension].", "content": "Vasorenal hypertension was induced in 2--3-month-old puppies and adult dogs by stricture of both renal arteries. 1.5 mg/kg of pyrroxan was injected intravenously 3 and 14 days later. A reduction of increased arterial pressure was noted both in adult dogs and in puppies, to the subnormal level in the latter. Hypotensive effect of the preparation was connected in adult animals with diminution of the general peripheral vascular resistance and in puppies, besides, with reduction of cardiac output. Pyrroxan injection was accompanied in all the animals with tachycardia, reduction of the phase of isometric contraction and activation of myocardial contractility.", "contents": "[Effect of the alpha-adrenoblocker pyrroxan on systemic hemodynamics in puppies and dogs with vasorenal hypertension]. Vasorenal hypertension was induced in 2--3-month-old puppies and adult dogs by stricture of both renal arteries. 1.5 mg/kg of pyrroxan was injected intravenously 3 and 14 days later. A reduction of increased arterial pressure was noted both in adult dogs and in puppies, to the subnormal level in the latter. Hypotensive effect of the preparation was connected in adult animals with diminution of the general peripheral vascular resistance and in puppies, besides, with reduction of cardiac output. Pyrroxan injection was accompanied in all the animals with tachycardia, reduction of the phase of isometric contraction and activation of myocardial contractility."}
{"id": "PMID:27263", "title": "[Pharmacology of azidomorphine].", "content": "As revealed, in acute experiments on rabbits, cats, and rats, a new morphine-like synthetic analgesic drug azidomorphine exceeded 20--100-fold the morphine ability to inhibit synaptic transmission in the thalamic structures, cerebral cortex, and the spinal cord during the nociceptive stimulation, and also by its analgesic activity.", "contents": "[Pharmacology of azidomorphine]. As revealed, in acute experiments on rabbits, cats, and rats, a new morphine-like synthetic analgesic drug azidomorphine exceeded 20--100-fold the morphine ability to inhibit synaptic transmission in the thalamic structures, cerebral cortex, and the spinal cord during the nociceptive stimulation, and also by its analgesic activity."}
{"id": "PMID:27264", "title": "Platelet storage at 22 degrees C: effect of type of agitation on morphology, viability, and function in vitro.", "content": "Recovery in vivo after 51Cr labeling, platelet morphology, and platelet aggregation were studied with platelet concentrates (PC) stored for transfusion under carefully controlled conditions. PC were prepared to a final volume of 50 ml from whole blood anticoagulated with citrate-phosphate-dextrose (CPD). The platelet count was kept between 0.8 and 1.6 X 10(12) platelets/liter. The PC were stored in bags constructed of polyvinylchloride (PVC) or polyethylene (PE) at 22 degrees C for 72 hr. The bags were placed on a horizontal shaker or a ferris wheel for agitation during storage. No significant changes in pH or platelet count were observed during storage. PC stored on the wheel showed moderate loss of viability and a marked deterioration of platelet morphology and aggregation compared to the shaker. PC stored on the shaker in bags made of PE showed better aggregation with ADP and thrombin but had the same viability and morphology as PC in bags constructed of PVC. Maintenance of normal platelet morphology as determined by phase-contrast microscopy, extent of shape change response, and the size distribution according to the Coulter Counter correlated with recovery in vivo.", "contents": "Platelet storage at 22 degrees C: effect of type of agitation on morphology, viability, and function in vitro. Recovery in vivo after 51Cr labeling, platelet morphology, and platelet aggregation were studied with platelet concentrates (PC) stored for transfusion under carefully controlled conditions. PC were prepared to a final volume of 50 ml from whole blood anticoagulated with citrate-phosphate-dextrose (CPD). The platelet count was kept between 0.8 and 1.6 X 10(12) platelets/liter. The PC were stored in bags constructed of polyvinylchloride (PVC) or polyethylene (PE) at 22 degrees C for 72 hr. The bags were placed on a horizontal shaker or a ferris wheel for agitation during storage. No significant changes in pH or platelet count were observed during storage. PC stored on the wheel showed moderate loss of viability and a marked deterioration of platelet morphology and aggregation compared to the shaker. PC stored on the shaker in bags made of PE showed better aggregation with ADP and thrombin but had the same viability and morphology as PC in bags constructed of PVC. Maintenance of normal platelet morphology as determined by phase-contrast microscopy, extent of shape change response, and the size distribution according to the Coulter Counter correlated with recovery in vivo."}
{"id": "PMID:27266", "title": "Neurochemical anatomy of the neuroendocrine hypothalamus. Neurochemical anatomy of the hypothalamus.", "content": "Microdissection techniques for isolated removal of the various regions of the hypothalamus as well as the individual hypothalamic nuclei are detailed. Recent development of biochemical microassays have made it possible that the concentrations of neurohormones, neuropeptides, neurotransmitters and their related enzymes could be detected in such a small volume of brain tissue than the hypothalamic nuclei. Data available of the hypothalamic distribution of above substances are summarized. The possible role and origin of intra- and extrahypothalamic neurohormones as well as the existence of the so-called \"hypophysiotrophic area\" are discussed.", "contents": "Neurochemical anatomy of the neuroendocrine hypothalamus. Neurochemical anatomy of the hypothalamus. Microdissection techniques for isolated removal of the various regions of the hypothalamus as well as the individual hypothalamic nuclei are detailed. Recent development of biochemical microassays have made it possible that the concentrations of neurohormones, neuropeptides, neurotransmitters and their related enzymes could be detected in such a small volume of brain tissue than the hypothalamic nuclei. Data available of the hypothalamic distribution of above substances are summarized. The possible role and origin of intra- and extrahypothalamic neurohormones as well as the existence of the so-called \"hypophysiotrophic area\" are discussed."}
{"id": "PMID:27267", "title": "Dopaminergic control of prolactin secretion.", "content": "A brief summary is given about present-day knowledge and views on the control of prolactin secretion in mammals. This is followed by the presentation of the evidence that dopamine is the inhibitory hypothalamic transducer controlling hormone release by prolactin cells. Most of the evidence is pharmacological in nature. It is only very recently that dopamine has been found in a meaningful concentration in the blood flowing from the median eminence to the pituitary. Although the dopamine concept of an inhibitory control of prolactin secretion seems quite satisfactory, the possibility of another unrelated inhibitory control system is not excluded.", "contents": "Dopaminergic control of prolactin secretion. A brief summary is given about present-day knowledge and views on the control of prolactin secretion in mammals. This is followed by the presentation of the evidence that dopamine is the inhibitory hypothalamic transducer controlling hormone release by prolactin cells. Most of the evidence is pharmacological in nature. It is only very recently that dopamine has been found in a meaningful concentration in the blood flowing from the median eminence to the pituitary. Although the dopamine concept of an inhibitory control of prolactin secretion seems quite satisfactory, the possibility of another unrelated inhibitory control system is not excluded."}
{"id": "PMID:27268", "title": "Hypothalamic regulatory hormones: physiological and clinical implications.", "content": "The hypothalamic regulatory hormones used for clinical studies are TRH, Gn-RH and somatostatin. In addition, as dopamine appears to be a physiological PIF, the dopamine agonists such as bromocriptine, could be considered as functional analogues of PIF. Gn-RH can be used to study the hypothalamic-pituitary gonadal relationship and to test the secretory reserve capacity of the gonadotrophs in disease states. Unfortunately Gn-RH testing discrimulates between pituitary and hypothalamic diseases only poorly. However gonadotrophin deficient men or women may be successfully treated with long-term Gn-RH with induction of puberty, potency, spermatogenesis and ovulation. Somatostatin has multiple actions in inhibiting endocrine and exocrine secretion but its actions are still being explored in diabetes. Bromocriptine, a long acting dopamine agonist (a functional analogue of PIF), suppresses prolactin and is highly effective in treating many hypogonadal states since hyperprolactinaemia is common. It also lowers growth hormone in acromegaly. TRH has provided a major, accurate, sensitive and safe test of thyroid function.", "contents": "Hypothalamic regulatory hormones: physiological and clinical implications. The hypothalamic regulatory hormones used for clinical studies are TRH, Gn-RH and somatostatin. In addition, as dopamine appears to be a physiological PIF, the dopamine agonists such as bromocriptine, could be considered as functional analogues of PIF. Gn-RH can be used to study the hypothalamic-pituitary gonadal relationship and to test the secretory reserve capacity of the gonadotrophs in disease states. Unfortunately Gn-RH testing discrimulates between pituitary and hypothalamic diseases only poorly. However gonadotrophin deficient men or women may be successfully treated with long-term Gn-RH with induction of puberty, potency, spermatogenesis and ovulation. Somatostatin has multiple actions in inhibiting endocrine and exocrine secretion but its actions are still being explored in diabetes. Bromocriptine, a long acting dopamine agonist (a functional analogue of PIF), suppresses prolactin and is highly effective in treating many hypogonadal states since hyperprolactinaemia is common. It also lowers growth hormone in acromegaly. TRH has provided a major, accurate, sensitive and safe test of thyroid function."}
{"id": "PMID:27269", "title": "[Pathophysiology of sulfatide metabolism in metachromatic leukodystrophy].", "content": "Metachromatic leucodystrophies (MLD) comprise a small group of heredodegenerative disorders of the nervous system. Deficiency of sulfatide-sulfatase or arylsulfatase A is the common defect in all forms of MLD leading to lysosomal sulfatide storage in the nervous tissue and in the kidney. On the basis of animal experiments, experiments with cultured fibroblasts of the patients as well as ultrastructural studies in a case of prenatal MLD, the following pathomechanism is proposed: 1. Lysosomal degradation of a large portion newly synthetised sulfatide normally regulating the net synthesis and incorporation of sulfatide into myelin, causes early accumulation of sulfatide in lysosomes of myelinating cells and in neurons in the genetic deficiency of arylsulfatase A. 2. Early accumulation of sulfatide does not lead to disturbance in myelination. Demyelination occurs possibly by storage of a cytotoxic compound, psychosin sulfate, also a substrate for the missing enzyme. Prevention of MLD is possible by prenatal diagnosis of arylsulfatase A deficiency in cultured amniotic cells. Enzyme substitution of the missing arylsulfatase A is possible by exogenous uptake of the enzyme in cultured fibroblasts. Thereby the defect of sulfatide degradation can be corrected. Although principles of enzyme substitution have been demonstrated, the problems of treating patients with MLD with arylsulfatase A infusions have yet to be overcome.", "contents": "[Pathophysiology of sulfatide metabolism in metachromatic leukodystrophy]. Metachromatic leucodystrophies (MLD) comprise a small group of heredodegenerative disorders of the nervous system. Deficiency of sulfatide-sulfatase or arylsulfatase A is the common defect in all forms of MLD leading to lysosomal sulfatide storage in the nervous tissue and in the kidney. On the basis of animal experiments, experiments with cultured fibroblasts of the patients as well as ultrastructural studies in a case of prenatal MLD, the following pathomechanism is proposed: 1. Lysosomal degradation of a large portion newly synthetised sulfatide normally regulating the net synthesis and incorporation of sulfatide into myelin, causes early accumulation of sulfatide in lysosomes of myelinating cells and in neurons in the genetic deficiency of arylsulfatase A. 2. Early accumulation of sulfatide does not lead to disturbance in myelination. Demyelination occurs possibly by storage of a cytotoxic compound, psychosin sulfate, also a substrate for the missing enzyme. Prevention of MLD is possible by prenatal diagnosis of arylsulfatase A deficiency in cultured amniotic cells. Enzyme substitution of the missing arylsulfatase A is possible by exogenous uptake of the enzyme in cultured fibroblasts. Thereby the defect of sulfatide degradation can be corrected. Although principles of enzyme substitution have been demonstrated, the problems of treating patients with MLD with arylsulfatase A infusions have yet to be overcome."}
{"id": "PMID:27271", "title": "Alteration of medullary respiratory unit discharge by iontophoretic application of putative neurotransmitters.", "content": "1 Cats with midcollicular decerebration were vagotomized, paralyzed and artificially ventilated. Phrenic nerve activity was recorded as an index of central respiratory rhythm. Medullary respiratory neurones and non-respiratory cells located in approximation to the ventral respiratory nucleus were tested for their responsiveness to iontophoretically applied gamma-aminobutyric acid (GABA), acetylcholine (ACh) and glutamate. 2 GABA tended to inhibit, whereas ACh and glutamate excited activity both of respiratory and non-respiratory units. Some phase-spanning respiratory unit activities were converted to phasic discharge patterns linked to either inspiration or expiration concomitant with application of low GABA doses. Appropriate applications of GABA also resulted in a complete cessation of the respiratory or non-respiratory neuronal activities. 3 While application of ACh or glutamate induced continuous firing in phasic, phase-spanning respiratory neurones, the periodic discharge patterns of inspiratory or expiratory units was not altered by ACh or, in many instances, by glutamate. Only at high doses of glutamate was the phasic discharge of some inspiratory or expiratory units converted to tonic activity. 4 These observations suggest that strong inhibitory processes serve to maintain the phasic firing pattern of respiratory units. These data also support the concept that active-inhibitory phase-switching mechanisms serve to define respiratory rhythmicity.", "contents": "Alteration of medullary respiratory unit discharge by iontophoretic application of putative neurotransmitters. 1 Cats with midcollicular decerebration were vagotomized, paralyzed and artificially ventilated. Phrenic nerve activity was recorded as an index of central respiratory rhythm. Medullary respiratory neurones and non-respiratory cells located in approximation to the ventral respiratory nucleus were tested for their responsiveness to iontophoretically applied gamma-aminobutyric acid (GABA), acetylcholine (ACh) and glutamate. 2 GABA tended to inhibit, whereas ACh and glutamate excited activity both of respiratory and non-respiratory units. Some phase-spanning respiratory unit activities were converted to phasic discharge patterns linked to either inspiration or expiration concomitant with application of low GABA doses. Appropriate applications of GABA also resulted in a complete cessation of the respiratory or non-respiratory neuronal activities. 3 While application of ACh or glutamate induced continuous firing in phasic, phase-spanning respiratory neurones, the periodic discharge patterns of inspiratory or expiratory units was not altered by ACh or, in many instances, by glutamate. Only at high doses of glutamate was the phasic discharge of some inspiratory or expiratory units converted to tonic activity. 4 These observations suggest that strong inhibitory processes serve to maintain the phasic firing pattern of respiratory units. These data also support the concept that active-inhibitory phase-switching mechanisms serve to define respiratory rhythmicity."}
{"id": "PMID:27272", "title": "Factors limiting the rate of termination of the neuromuscular blocking action of fazadinium dibromide.", "content": "1 Reasons for the termination of the neuromuscular blocking action of fazadinium dibromide have been investigated. 2 In the anaesthetized cat, maximum neuromuscular block of tibialis anterior muscle twitches following rapid intravenous injection of fazadinium was obtained as the injection bolus passed through the muscle, indicating the fazadinium very readily crosses capillary membranes. 3. The half-life of plasma clearance of fazadinium was about 1 min in both cat and man, despite a 10 fold difference in duration of action in these species. Plasma samples were bioassayed for neuromuscular blocking activity on an isolated, superfused phrenic nerve-diaphragm preparation of the rat. 4 In the anaesthetized cat, occlusion of the renal or hepatic circulations did not prolong the neuromuscular blocking action of single doses of fazadinium. Repeated doses accumulated slowly when the hepatic circulation was occluded but not when the renal circulation was occluded. 5 Fazadinium is eliminated from the body by both the liver and kidneys but the rates of these processes are insufficient to account for the initial rapid plasma clearance. 6 The rate-limiting step for the termination of the neuromuscular blocking action of fazadinium is most likely to be the rate of drug-receptor dissociation", "contents": "Factors limiting the rate of termination of the neuromuscular blocking action of fazadinium dibromide. 1 Reasons for the termination of the neuromuscular blocking action of fazadinium dibromide have been investigated. 2 In the anaesthetized cat, maximum neuromuscular block of tibialis anterior muscle twitches following rapid intravenous injection of fazadinium was obtained as the injection bolus passed through the muscle, indicating the fazadinium very readily crosses capillary membranes. 3. The half-life of plasma clearance of fazadinium was about 1 min in both cat and man, despite a 10 fold difference in duration of action in these species. Plasma samples were bioassayed for neuromuscular blocking activity on an isolated, superfused phrenic nerve-diaphragm preparation of the rat. 4 In the anaesthetized cat, occlusion of the renal or hepatic circulations did not prolong the neuromuscular blocking action of single doses of fazadinium. Repeated doses accumulated slowly when the hepatic circulation was occluded but not when the renal circulation was occluded. 5 Fazadinium is eliminated from the body by both the liver and kidneys but the rates of these processes are insufficient to account for the initial rapid plasma clearance. 6 The rate-limiting step for the termination of the neuromuscular blocking action of fazadinium is most likely to be the rate of drug-receptor dissociation"}
{"id": "PMID:27279", "title": "Evidence for the participation of beta1-adrenoceptors in isoprenaline-induced renin release from rat kidny slices in vitro.", "content": "1. The inhibitory effects were studied of 4 beta-adrenoceptor antagonists against renin release induced by isoprenaline (0.5 mumol/1) in rat kidney slices. Additionally the pA2 values of these 4 drugs were measured against isoprenaline in guinea-pig isolated atria and trachea (against beta1- and beta2-adrenoceptors respectively). 2 When employed at a concentration of 2 mumol/1 propranolol and atenolol significantly inhibited renin release (P less than 0.001 and P less than 0.01) whereas practolol and IPS 339 [t-butyl-amino-3 ol-2 propyl) oximino-9 fluorene] had little effect. 2 A positive correlation was shown between the degree of inhibition of renin release and the pA2 of the antagonists at the beta1-adrenoceptors. 4 When practolol and IPS 339 were used in equipotent molar concentrations to propranolol for the beta1-adrenoceptors they inhibited renin release. 5 The results suggest that the adrenoceptor involved in the renin release induced by isoprenaline in the rat kidney is of the beta1-type.", "contents": "Evidence for the participation of beta1-adrenoceptors in isoprenaline-induced renin release from rat kidny slices in vitro. 1. The inhibitory effects were studied of 4 beta-adrenoceptor antagonists against renin release induced by isoprenaline (0.5 mumol/1) in rat kidney slices. Additionally the pA2 values of these 4 drugs were measured against isoprenaline in guinea-pig isolated atria and trachea (against beta1- and beta2-adrenoceptors respectively). 2 When employed at a concentration of 2 mumol/1 propranolol and atenolol significantly inhibited renin release (P less than 0.001 and P less than 0.01) whereas practolol and IPS 339 [t-butyl-amino-3 ol-2 propyl) oximino-9 fluorene] had little effect. 2 A positive correlation was shown between the degree of inhibition of renin release and the pA2 of the antagonists at the beta1-adrenoceptors. 4 When practolol and IPS 339 were used in equipotent molar concentrations to propranolol for the beta1-adrenoceptors they inhibited renin release. 5 The results suggest that the adrenoceptor involved in the renin release induced by isoprenaline in the rat kidney is of the beta1-type."}
{"id": "PMID:27280", "title": "The effects of isoprenaline and a new beta-sympathomimetic amine upon spontaneous activity, diastolic depolarization and plateau height in cardiac Purkinje fibres.", "content": "1 In spontaneously active Purkinje fibres of young cows the dose-response curves of the action of isoprenaline upon different electrophysiological parameters were measured.2 The increase in slope of diastolic depolarization could roughly be described by a one-for-one binding curve with a half maximum effect near 10(-8) M and the increase in the height of the plateau level by a two-for-one binding curve with a half maximum effect near 10(-7) M (-)-isoprenaline.3 These dose-response curves were similar to those of two parameters measured under voltage clamp conditions by other authors. The increase in slope of diastolic depolarization behaved like the shift of the activation curve for the pacemaker potassium current towards positive potentials and the growth in plateau height like the increase in the slow inward current mainly carried by Ca ions. From this conformity we propose that the parameters evaluated by us from action potential records could be used for a qualitative analysis of the action of catecholamines on pacemaker potassium current and Ca influx.4 The effects of the isomers of a new drug, 1-isopropylamino-3(4'hydroxyphenoxy)-propan-2-ol (IHP), were evaluated in the same way as those of isoprenaline. The (-)-isomer was at optimal concentrations (10(-5) M) nearly half as effective as isoprenaline in increasing frequency and slope of diastolic depolarization but caused no increase in plateau height. An identical relationship, but at 5 to 10 times higher concentrations, was obtained with the (+)-isomer.5 When 10(-4) M(-)-IHP was added to a preparation equilibrated with a maximum dose of (-)-isoprenaline (10(-6) M), frequency and plateau height declined. This result together with the observation that the effects of IHP could be blocked by the specific beta-antagonist propranolol, revealed the beta-agonistic nature of the new drug. Its inefficiency in increasing the plateau height and thus the slow (Ca) inward current was explained by its relatively low potency and intrinsic activity.", "contents": "The effects of isoprenaline and a new beta-sympathomimetic amine upon spontaneous activity, diastolic depolarization and plateau height in cardiac Purkinje fibres. 1 In spontaneously active Purkinje fibres of young cows the dose-response curves of the action of isoprenaline upon different electrophysiological parameters were measured.2 The increase in slope of diastolic depolarization could roughly be described by a one-for-one binding curve with a half maximum effect near 10(-8) M and the increase in the height of the plateau level by a two-for-one binding curve with a half maximum effect near 10(-7) M (-)-isoprenaline.3 These dose-response curves were similar to those of two parameters measured under voltage clamp conditions by other authors. The increase in slope of diastolic depolarization behaved like the shift of the activation curve for the pacemaker potassium current towards positive potentials and the growth in plateau height like the increase in the slow inward current mainly carried by Ca ions. From this conformity we propose that the parameters evaluated by us from action potential records could be used for a qualitative analysis of the action of catecholamines on pacemaker potassium current and Ca influx.4 The effects of the isomers of a new drug, 1-isopropylamino-3(4'hydroxyphenoxy)-propan-2-ol (IHP), were evaluated in the same way as those of isoprenaline. The (-)-isomer was at optimal concentrations (10(-5) M) nearly half as effective as isoprenaline in increasing frequency and slope of diastolic depolarization but caused no increase in plateau height. An identical relationship, but at 5 to 10 times higher concentrations, was obtained with the (+)-isomer.5 When 10(-4) M(-)-IHP was added to a preparation equilibrated with a maximum dose of (-)-isoprenaline (10(-6) M), frequency and plateau height declined. This result together with the observation that the effects of IHP could be blocked by the specific beta-antagonist propranolol, revealed the beta-agonistic nature of the new drug. Its inefficiency in increasing the plateau height and thus the slow (Ca) inward current was explained by its relatively low potency and intrinsic activity."}
{"id": "PMID:27281", "title": "Enhancement by an antagonist of transmitter release from frog motor nerve terminals.", "content": "1 The effect of Ba2+ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques. 2 When Ca2+ and Ba2+ were the only divalent cations in the bathing fluid, Ba2+ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca2+ concentration. 3 The affinity constant (KA) for Ba2+, calculated on the assumption that Ba2+ is a competitive inhibitor of the agonist, Ca2+, was 1.1 +/- 0.4 mM-1 (mean +/- s.e. mean, n = 8). 4 When e.p.ps were depressed by the addition of 1 mM Mg2+, addition of Ba2+ (1 to 3 mM) caused either a further presynaptic depression of moderate magnitude or had no additional effect. 5 When e.p.p.s were depressed with [Mg2+] greater than or equal to 2 mM, addition of Ba2+ greater than or equal to 0.9 mM enhanced the e.p.p. amplitude by a presynaptic mechanism. 6 The interaction of the divalent cation antagonists Mg2+ and Ba2+ with the agonist, Ca2+ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending.", "contents": "Enhancement by an antagonist of transmitter release from frog motor nerve terminals. 1 The effect of Ba2+ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques. 2 When Ca2+ and Ba2+ were the only divalent cations in the bathing fluid, Ba2+ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca2+ concentration. 3 The affinity constant (KA) for Ba2+, calculated on the assumption that Ba2+ is a competitive inhibitor of the agonist, Ca2+, was 1.1 +/- 0.4 mM-1 (mean +/- s.e. mean, n = 8). 4 When e.p.ps were depressed by the addition of 1 mM Mg2+, addition of Ba2+ (1 to 3 mM) caused either a further presynaptic depression of moderate magnitude or had no additional effect. 5 When e.p.p.s were depressed with [Mg2+] greater than or equal to 2 mM, addition of Ba2+ greater than or equal to 0.9 mM enhanced the e.p.p. amplitude by a presynaptic mechanism. 6 The interaction of the divalent cation antagonists Mg2+ and Ba2+ with the agonist, Ca2+ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending."}
{"id": "PMID:27283", "title": "Rat cortical neurons in cell culture: culture methods, cell morphology, electrophysiology, and synapse formation.", "content": "Rat cortical neurons from 15 day embryos are grown in dissociated cell culture and maintained in vitro for 8--12 weeks. The neurons develop into forms which resemble mature cortical neurons in situ, stain with silver and exhibit passive and active electrophysiological properties similar to those of cortical neurons. Extensive chemical excitatory and inhibitory synapses develop de novo. These cultures can provide a model for future studies of mammalian CNS neuronal physiology, transmitter pharmacology, pathophysiology and mechanisms of drug action.", "contents": "Rat cortical neurons in cell culture: culture methods, cell morphology, electrophysiology, and synapse formation. Rat cortical neurons from 15 day embryos are grown in dissociated cell culture and maintained in vitro for 8--12 weeks. The neurons develop into forms which resemble mature cortical neurons in situ, stain with silver and exhibit passive and active electrophysiological properties similar to those of cortical neurons. Extensive chemical excitatory and inhibitory synapses develop de novo. These cultures can provide a model for future studies of mammalian CNS neuronal physiology, transmitter pharmacology, pathophysiology and mechanisms of drug action."}
{"id": "PMID:27284", "title": "The use of kainic acid in the localization of enzymes in the substantia nigra.", "content": "The selective destruction of neuronal perikarya via intracerebral injections of kainic acid was used to elucidate the cellular location of four neurotransmitter-related enzymes in the substantia nigra (SN). Two weeks after intranigral injections of kainic acid, dopamine-sensitive adenylate cyclase, glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in the SN. Histological examination of the SN, and a reduction of striatal tyrosine hydroxylase (TH) activity by 94%, confirmed the extensive loss of neuronal cell bodies in the SN. Dopamine stimulation of adenylate cyclase was not reduced in the lesioned SN, supporting the view that dendritically-released dopamine can regulate cyclic AMP synthesis in afferent terminals to these dendrites. Nigral GAD activity was significantly reduced by the lesions, suggesting that there are GAD-containing perikarya in the SN. CAT activity was not affected by the kainic injections, indicating the absence of cholinergic perikarya in the SN. Nigral AChE activity was significantly decreased after kainic injections, thus confirming the presence of AChE within the nigral perikarya. The results suggest that dopamine-sensitive adenylate cyclase and CAT are located within afferents to the SN, while GAD and AChE are found, to some extent at least, in neuronal soma of the SN. The differentail effects of kainic acid on these enzymes suggest that this compound may be a useful neurochemical tool with which to determine the cellular distribution of enzyme systems in the central nervous system.", "contents": "The use of kainic acid in the localization of enzymes in the substantia nigra. The selective destruction of neuronal perikarya via intracerebral injections of kainic acid was used to elucidate the cellular location of four neurotransmitter-related enzymes in the substantia nigra (SN). Two weeks after intranigral injections of kainic acid, dopamine-sensitive adenylate cyclase, glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in the SN. Histological examination of the SN, and a reduction of striatal tyrosine hydroxylase (TH) activity by 94%, confirmed the extensive loss of neuronal cell bodies in the SN. Dopamine stimulation of adenylate cyclase was not reduced in the lesioned SN, supporting the view that dendritically-released dopamine can regulate cyclic AMP synthesis in afferent terminals to these dendrites. Nigral GAD activity was significantly reduced by the lesions, suggesting that there are GAD-containing perikarya in the SN. CAT activity was not affected by the kainic injections, indicating the absence of cholinergic perikarya in the SN. Nigral AChE activity was significantly decreased after kainic injections, thus confirming the presence of AChE within the nigral perikarya. The results suggest that dopamine-sensitive adenylate cyclase and CAT are located within afferents to the SN, while GAD and AChE are found, to some extent at least, in neuronal soma of the SN. The differentail effects of kainic acid on these enzymes suggest that this compound may be a useful neurochemical tool with which to determine the cellular distribution of enzyme systems in the central nervous system."}
{"id": "PMID:27286", "title": "Evidence for glutamate as a neurotransmitter in the corticofugal fibres to the dorsal lateral geniculate body and the superior colliculus in rats.", "content": "The high-affinity uptake of L-glutamate, D-aspartate and GABA were examined in homogenates from the dorsal lateral geniculate body and the superior colliculus after removal of the right visual cortex of adult rats. The high-affinity uptake of D-aspartate and L-glutamate were reduced by 53 to 75% respectively in the dorsal lateral geniculate body and by 46 and 53% respectively in the superior colliculus ipsilateral to the lesion. The uptake on the contralateral side was unaffected. The reductions were detected 3 days after the lesion and were maximally developed after 7 days. Subcellular fractionation showed that the main part of the uptake was confined to the synaptosomal fraction of both regions and that the reductions were most prominent in this fraction. The lesion was not accompanied by significant changes in high-affinity uptake of GABA nor in changes of choline acetyltransferase and glutamate decarboxylase activities. The high-affinity L-glutamate uptake on the contralateral visual cortex was unchanged from control values. After ablation of the visual cortex the level of L-glutamate was reduced by 32 and 17% in the ipsilateral dorsal lateral geniculate body and superior colliculus, respectively. The levels of the other amino acids examined, including L-aspartate, were unchanged. Enucleation had no effect on the uptake of L-glutamate and of GABA in the dorsal lateral geniculate body or in the superior colliculus.", "contents": "Evidence for glutamate as a neurotransmitter in the corticofugal fibres to the dorsal lateral geniculate body and the superior colliculus in rats. The high-affinity uptake of L-glutamate, D-aspartate and GABA were examined in homogenates from the dorsal lateral geniculate body and the superior colliculus after removal of the right visual cortex of adult rats. The high-affinity uptake of D-aspartate and L-glutamate were reduced by 53 to 75% respectively in the dorsal lateral geniculate body and by 46 and 53% respectively in the superior colliculus ipsilateral to the lesion. The uptake on the contralateral side was unaffected. The reductions were detected 3 days after the lesion and were maximally developed after 7 days. Subcellular fractionation showed that the main part of the uptake was confined to the synaptosomal fraction of both regions and that the reductions were most prominent in this fraction. The lesion was not accompanied by significant changes in high-affinity uptake of GABA nor in changes of choline acetyltransferase and glutamate decarboxylase activities. The high-affinity L-glutamate uptake on the contralateral visual cortex was unchanged from control values. After ablation of the visual cortex the level of L-glutamate was reduced by 32 and 17% in the ipsilateral dorsal lateral geniculate body and superior colliculus, respectively. The levels of the other amino acids examined, including L-aspartate, were unchanged. Enucleation had no effect on the uptake of L-glutamate and of GABA in the dorsal lateral geniculate body or in the superior colliculus."}
{"id": "PMID:27287", "title": "Receptor-linked cyclic AMP systems in rat neostriatum: differential localization revealed by kainic acid injection.", "content": "Various receptor-linked cyclic AMP systems were measured in rat neostriatum 2--14 days after selective destruction of neuronal cell bodies and dendrites by micro-injection of 3 microgram of kainic acid. Basal adenylate cyclase activity was reduced by up to 56% in the injected side and the sensitivity to dopamine was abolished. Up to 84% of cyclic nucleotide phosphodiesterase activity, hydrolyzing either cyclic AMP or cyclic GMP, was destroyed by kainic acid injection. Specific binding of [3H]etorphine and [3H]spiroperidol was reduced by up to 62% in the injected side, while non-specific binding was unchanged. All of these changes were time-dependent, and were greatest 7--14 days after kainic acid treatment. On the other hand, intrastriatal kainic acid injection caused no change in the steady-state concentration of cyclic AMP in striatal slices, or in the in vivo cyclic AMP content in the striatum of rats killed by microwave irradiation. Receptor-mediated increases in cyclic AMP accumulation in striatal slices were either unchanged or markedly potentiated by kainic acid treatment. The maximum response to adenosine was unchanged, while the response to isoprenaline was increased up to 3.7-fold, the response to dopamine increased up to 6.7-fold, and the response to PGE1 increased up to 30-fold. The effect of dopamine in kainic acid-treated striatal slices was no longer blocked by fluphenazine, but was blocked by propranolol, suggesting an interaction of dopamine with a beta-adrenoceptor in kainic acid-treated slices. The results suggest differential cellular localizations of the various receptor-linked cyclic AMP systems in rat neostriatum. Some dopamine and opiate receptors, as well as most of the phosphodiesterase activity, are associated with local neuronal elements, while beta-adrenoceptor, adenosine and PGE1 alterations in cyclic AMP are not. The potentiation of the beta-adrenoceptor and PGE1 responses suggests that they may occur in glial cells. In addition, the pool of adenylate cyclase destroyed by kainic acid appears to make little contribution to normal levels of cyclic AMP in the tissue.", "contents": "Receptor-linked cyclic AMP systems in rat neostriatum: differential localization revealed by kainic acid injection. Various receptor-linked cyclic AMP systems were measured in rat neostriatum 2--14 days after selective destruction of neuronal cell bodies and dendrites by micro-injection of 3 microgram of kainic acid. Basal adenylate cyclase activity was reduced by up to 56% in the injected side and the sensitivity to dopamine was abolished. Up to 84% of cyclic nucleotide phosphodiesterase activity, hydrolyzing either cyclic AMP or cyclic GMP, was destroyed by kainic acid injection. Specific binding of [3H]etorphine and [3H]spiroperidol was reduced by up to 62% in the injected side, while non-specific binding was unchanged. All of these changes were time-dependent, and were greatest 7--14 days after kainic acid treatment. On the other hand, intrastriatal kainic acid injection caused no change in the steady-state concentration of cyclic AMP in striatal slices, or in the in vivo cyclic AMP content in the striatum of rats killed by microwave irradiation. Receptor-mediated increases in cyclic AMP accumulation in striatal slices were either unchanged or markedly potentiated by kainic acid treatment. The maximum response to adenosine was unchanged, while the response to isoprenaline was increased up to 3.7-fold, the response to dopamine increased up to 6.7-fold, and the response to PGE1 increased up to 30-fold. The effect of dopamine in kainic acid-treated striatal slices was no longer blocked by fluphenazine, but was blocked by propranolol, suggesting an interaction of dopamine with a beta-adrenoceptor in kainic acid-treated slices. The results suggest differential cellular localizations of the various receptor-linked cyclic AMP systems in rat neostriatum. Some dopamine and opiate receptors, as well as most of the phosphodiesterase activity, are associated with local neuronal elements, while beta-adrenoceptor, adenosine and PGE1 alterations in cyclic AMP are not. The potentiation of the beta-adrenoceptor and PGE1 responses suggests that they may occur in glial cells. In addition, the pool of adenylate cyclase destroyed by kainic acid appears to make little contribution to normal levels of cyclic AMP in the tissue."}
{"id": "PMID:27288", "title": "Effects of estrogen and aminergic drugs on thresholds of medial basal hypothalamic axons in the median eminence of the rat.", "content": "Antidromic responses were induced in the medial basal hypothalamus (MBH) of female rats by median eminence (ME) stimulation, and thresholds were measured under various endocrine conditions. Two different types of antidromic response were recognized. In 83 out of 97 responses, repetitive shocks to the ME at 20--40 Hz induced a fractionation of antidromically-driven spikes into A- and B-components. In the remainder, the antidromically activated spikes were stable to stimulation at high frequency. The threshold tended to show higher values in proestrus than in diestrus-I in both types of response. However, only in the former type of response, application of conditioning electrical shocks to the ME was effective in decreasing the threshold for successive test pulses. A decrease in the threshold lasted for 150--200 msec following the conditioning, with the lowest threshold at about 60 msec after the shock. Effects of the conditioning persisted in animals with chronic complete deafferentation of the MBH but were abolished in intact rats by reserpine treatment. Dopamine, but not norepinephrine or serotonin, mimicked the threshold-decreasing effect of the conditioning when applied to the ME. The results suggest the possibility of a depolarizing effect of some dopaminergic neural mechanism projecting from the MBH to the ME and acting on the axons of a particular type of MBH neuron characterized by fractionating spikes.", "contents": "Effects of estrogen and aminergic drugs on thresholds of medial basal hypothalamic axons in the median eminence of the rat. Antidromic responses were induced in the medial basal hypothalamus (MBH) of female rats by median eminence (ME) stimulation, and thresholds were measured under various endocrine conditions. Two different types of antidromic response were recognized. In 83 out of 97 responses, repetitive shocks to the ME at 20--40 Hz induced a fractionation of antidromically-driven spikes into A- and B-components. In the remainder, the antidromically activated spikes were stable to stimulation at high frequency. The threshold tended to show higher values in proestrus than in diestrus-I in both types of response. However, only in the former type of response, application of conditioning electrical shocks to the ME was effective in decreasing the threshold for successive test pulses. A decrease in the threshold lasted for 150--200 msec following the conditioning, with the lowest threshold at about 60 msec after the shock. Effects of the conditioning persisted in animals with chronic complete deafferentation of the MBH but were abolished in intact rats by reserpine treatment. Dopamine, but not norepinephrine or serotonin, mimicked the threshold-decreasing effect of the conditioning when applied to the ME. The results suggest the possibility of a depolarizing effect of some dopaminergic neural mechanism projecting from the MBH to the ME and acting on the axons of a particular type of MBH neuron characterized by fractionating spikes."}
{"id": "PMID:27291", "title": "Calcium-binding properties of cardiac and skeletal troponin C as determined by circular dichroism and ultraviolet difference spectroscopy.", "content": "Calcium titration of the conformational change in cardiac and skeletal troponin C (TN-C) was followed by circular dichroism (CD) at pH values in the range from 5.2 to 7.4. Computer analysis was used to resolve the contributions from the different classes of Ca2+ -binding sites. At pH 6.94 in skeletal TN-C, apparent affinity constants for calcium of 1.8 x 10(7) and 4.5 x 10(5) M-1 were determined for the two classes of binding sites. The more sophisticated computer analysis of the data has revealed a substantial CD contribution from the low-affinity sites (approximately 30% of the high affinity contribution at pH 6.94) and suggests that skeletal TN-C with Ca2+ bound at the low-affinity sites is in a different conformation from that when just the high-affinity sites are occupied, in agreement with a recent nuclear magnetic resonance (NMR) study on this system (Seaman, K. B., Hartshorne, D. J. & Bothener-By, A. A. (1977) Biochemistry 16,4039-4046). With the cardiac protein at pH 7.07, an apparent affinity constant for calcium of 2.0 x 10(7) M-1 was calculated while no low-affinity site at this pH was detected by CD. On the other hand, at lower pH values, such as 6.05, a CD contribution from the cardiac low-affinity Ca2+ -binding site is detected with an apparent binding constant of 3.7 +/- 0.7 x 10(4) M-1. At the lower pH values, protonation of a class of carboxyl groups in each protein which possesses a high pKa (6.2-6.3) elicits the conformational change at the high-affinity sites with a corresponding decrease in the overall magnitude of the Ca2+  -evoked changes. The expression of a conformational change upon Ca2+ binding at the level of the low-affinity sites is enchanced by protonation of a class of carboxyls with a pKa of 6.3 in cardiac TN-C and 6.7-6.8 with the skeletal homologue. In both cases, this contribution is reduced upon protonation of carboxyls with pKa less than or equal to 5.5. It was also observed that the low-affinity sites of skeletal TN-C have a much larger role to play in the total conformational change than the low-affinity sites of cardiac TN-C, a finding probably related to the inability of site 1 in the cardiac protein to bind calcium. In the cardiac protein, the Ca2+ -induced tyrosine difference-spectrum maximum is reduced from deltaepsilonM,287nm =330M-1.cm-1 to 20M-1.cm-1 by protonation of a class of groups with a pKa of 6.4, presumably the same carboxyl groups as those invoved in the CD conformational contribution from the high-affinity binding sites. No such effect was observed for the skeletal protein where deltaepsilonM,287nm was constant at 110M-1 .cm-1 over the pH range studied. The dramatic alterations in the tyrosine environment of cardiac TN-C with pH are attributed to either or both of the tyrosines located in the two high-affinity Ca2+ -binding sites (sites 3 and 4)...", "contents": "Calcium-binding properties of cardiac and skeletal troponin C as determined by circular dichroism and ultraviolet difference spectroscopy. Calcium titration of the conformational change in cardiac and skeletal troponin C (TN-C) was followed by circular dichroism (CD) at pH values in the range from 5.2 to 7.4. Computer analysis was used to resolve the contributions from the different classes of Ca2+ -binding sites. At pH 6.94 in skeletal TN-C, apparent affinity constants for calcium of 1.8 x 10(7) and 4.5 x 10(5) M-1 were determined for the two classes of binding sites. The more sophisticated computer analysis of the data has revealed a substantial CD contribution from the low-affinity sites (approximately 30% of the high affinity contribution at pH 6.94) and suggests that skeletal TN-C with Ca2+ bound at the low-affinity sites is in a different conformation from that when just the high-affinity sites are occupied, in agreement with a recent nuclear magnetic resonance (NMR) study on this system (Seaman, K. B., Hartshorne, D. J. & Bothener-By, A. A. (1977) Biochemistry 16,4039-4046). With the cardiac protein at pH 7.07, an apparent affinity constant for calcium of 2.0 x 10(7) M-1 was calculated while no low-affinity site at this pH was detected by CD. On the other hand, at lower pH values, such as 6.05, a CD contribution from the cardiac low-affinity Ca2+ -binding site is detected with an apparent binding constant of 3.7 +/- 0.7 x 10(4) M-1. At the lower pH values, protonation of a class of carboxyl groups in each protein which possesses a high pKa (6.2-6.3) elicits the conformational change at the high-affinity sites with a corresponding decrease in the overall magnitude of the Ca2+  -evoked changes. The expression of a conformational change upon Ca2+ binding at the level of the low-affinity sites is enchanced by protonation of a class of carboxyls with a pKa of 6.3 in cardiac TN-C and 6.7-6.8 with the skeletal homologue. In both cases, this contribution is reduced upon protonation of carboxyls with pKa less than or equal to 5.5. It was also observed that the low-affinity sites of skeletal TN-C have a much larger role to play in the total conformational change than the low-affinity sites of cardiac TN-C, a finding probably related to the inability of site 1 in the cardiac protein to bind calcium. In the cardiac protein, the Ca2+ -induced tyrosine difference-spectrum maximum is reduced from deltaepsilonM,287nm =330M-1.cm-1 to 20M-1.cm-1 by protonation of a class of groups with a pKa of 6.4, presumably the same carboxyl groups as those invoved in the CD conformational contribution from the high-affinity binding sites. No such effect was observed for the skeletal protein where deltaepsilonM,287nm was constant at 110M-1 .cm-1 over the pH range studied. The dramatic alterations in the tyrosine environment of cardiac TN-C with pH are attributed to either or both of the tyrosines located in the two high-affinity Ca2+ -binding sites (sites 3 and 4)..."}
{"id": "PMID:27292", "title": "Guanosine triphosphate catabolism in human and rabbit erythrocytes: role of reductive deamination of guanylate to inosinate.", "content": "The reductive deamination of guanylate to inosinate was demonstrable but occurred at low rates in human and rabbit erythrocytes incubated in vitro with or without glucose. However, the process was considerably accelerated in erythrocytes incubated with deoxyglucose. In human erythrocytes incubated with deoxyglucose, deamination was the major pathway of catabolism of guanylate; little or no guanylate was dephosphorylated. In rabbit erythrocytes, guanylate was both deaminated and dephosphorylated. Inosinate formed from guanylate was metabolized only by dephosphorylation in human erythrocytes, but in rabbit erythrocytes, it was also converted to xanthylate.", "contents": "Guanosine triphosphate catabolism in human and rabbit erythrocytes: role of reductive deamination of guanylate to inosinate. The reductive deamination of guanylate to inosinate was demonstrable but occurred at low rates in human and rabbit erythrocytes incubated in vitro with or without glucose. However, the process was considerably accelerated in erythrocytes incubated with deoxyglucose. In human erythrocytes incubated with deoxyglucose, deamination was the major pathway of catabolism of guanylate; little or no guanylate was dephosphorylated. In rabbit erythrocytes, guanylate was both deaminated and dephosphorylated. Inosinate formed from guanylate was metabolized only by dephosphorylation in human erythrocytes, but in rabbit erythrocytes, it was also converted to xanthylate."}
{"id": "PMID:27293", "title": "Some properties of a Ca2+- and (or) Mg2+-requiring nucleoside di- and tri-phosphatase(s) associated with the membranes of rat pancreatic zymogen granules.", "content": "Membranes of rat pancreatic zymogen granules have been purified and found to be essentially free of contamination by mitochondria, microsomes, and plasma membranes. They possessed an acid phosphatase activity which derived probably from lysed lysosomes contaminating the purified zymogen granules from which the membranes were prepared. These membranes were found to contain a strong Ca2+- and (or) Mg2+-requiring activity toward all nucleoside di- and tri-phosphates. Various data support the tentative conclusion that a single protein catalyzes the hydrolysis of the nucleoside di- and tri-phosphates. This protein appears to be intrinsic with its active site localized on the internal face of the membranes.", "contents": "Some properties of a Ca2+- and (or) Mg2+-requiring nucleoside di- and tri-phosphatase(s) associated with the membranes of rat pancreatic zymogen granules. Membranes of rat pancreatic zymogen granules have been purified and found to be essentially free of contamination by mitochondria, microsomes, and plasma membranes. They possessed an acid phosphatase activity which derived probably from lysed lysosomes contaminating the purified zymogen granules from which the membranes were prepared. These membranes were found to contain a strong Ca2+- and (or) Mg2+-requiring activity toward all nucleoside di- and tri-phosphates. Various data support the tentative conclusion that a single protein catalyzes the hydrolysis of the nucleoside di- and tri-phosphates. This protein appears to be intrinsic with its active site localized on the internal face of the membranes."}
{"id": "PMID:27294", "title": "The control of pyruvate kinases of Escherichia coli: further studies of the enzyme activated by ribose-5-phosphate.", "content": "The pyruvate kinase activated by ribose-5-phosphate from Escherichia coli has been purified to homogeneity, taking advantage of the stabilization of the enzyme by its inhibitor phosphate and by thiol reagents. The native enzyme has a tetrameric quaternary structure which, while prone to dissociation under many conditions, remains intact in the presence of the above reagents. The enzyme was found to reactivate on dilution out of 8 M urea. Interestingly, the recovery of activity is greatly increased by phosphate, an allosteric inhibitor, but markedly reduced by the allosteric activator, ribose-5-phosphate, implying that it is harder for the enzyme to refold to a 'relaxed state.' Proteolysis studies indicate a more open structure in the presence of the activator.", "contents": "The control of pyruvate kinases of Escherichia coli: further studies of the enzyme activated by ribose-5-phosphate. The pyruvate kinase activated by ribose-5-phosphate from Escherichia coli has been purified to homogeneity, taking advantage of the stabilization of the enzyme by its inhibitor phosphate and by thiol reagents. The native enzyme has a tetrameric quaternary structure which, while prone to dissociation under many conditions, remains intact in the presence of the above reagents. The enzyme was found to reactivate on dilution out of 8 M urea. Interestingly, the recovery of activity is greatly increased by phosphate, an allosteric inhibitor, but markedly reduced by the allosteric activator, ribose-5-phosphate, implying that it is harder for the enzyme to refold to a 'relaxed state.' Proteolysis studies indicate a more open structure in the presence of the activator."}
{"id": "PMID:27297", "title": "Effect of pH on the antimicrobial activity of some triphenylmethane dyes.", "content": "Four common dyes were tested as inhibitors of four types of bacteria over the pH range 5.0-9.0. Inhibition of the gram-negative types, Salmonella anatum and Enterobacter aerogenes, was markedly affected by the pH of the medium. These organisms tolerated concentrations of crystal violet and ethyl violet about 100-fold higher at pH 5.0 than at pH 9.0. Above pH 7.0 brilliant green (BG) and malachite green (MG) were precipitated as their respective carbinols and lost their inhibitory properties with these two organisms. Two gram-positive types, Staphylococcus aureus and Bacillus cereus, were more sensitive to dyes and results were less affected by pH. The carbinol forms of MG and BG were nearly as inhibitory to these organisms as the ionized forms.", "contents": "Effect of pH on the antimicrobial activity of some triphenylmethane dyes. Four common dyes were tested as inhibitors of four types of bacteria over the pH range 5.0-9.0. Inhibition of the gram-negative types, Salmonella anatum and Enterobacter aerogenes, was markedly affected by the pH of the medium. These organisms tolerated concentrations of crystal violet and ethyl violet about 100-fold higher at pH 5.0 than at pH 9.0. Above pH 7.0 brilliant green (BG) and malachite green (MG) were precipitated as their respective carbinols and lost their inhibitory properties with these two organisms. Two gram-positive types, Staphylococcus aureus and Bacillus cereus, were more sensitive to dyes and results were less affected by pH. The carbinol forms of MG and BG were nearly as inhibitory to these organisms as the ionized forms."}
{"id": "PMID:27299", "title": "Reduced nicotinamide adenine dinucleotide phosphate-dependent formation of 2,3-dihydro-2,3-dihydroxyaflatoxin B1 from aflatoxin B1 by hepatic microsomes.", "content": "2,3-Dihydro-2,3-dihydroxyaflatoxin B1 (dihydrodiol) was formed as a major metabolite in the incubation of aflatoxin B1 with rat and hamster liver microsomes. The yield of the dihydrodiol was maximal at pH 6.5, was reduced nicotinmide adenine dinucleotide phosphate- and cytochrome P-450-dependent, and was increased 2- to 4-fold by pretreatment of the animals with phenobarbital; pretreatment with 3-methylcholanthrene did not alter the activity of rat hepatic microsomes. Inhibitors of epoxide hydrase did not lower the yield of the dihydrodiol in these systems. Negligible yields of the dihydrodiol were formed from aflatoxin B1 and rat liver microsomes in the presence of DNA. Little or no formation of the dihydrodiol was noted with microsomes from rat intestinal mucosa, kidney, or lung. These results further support the formation of aflatoxin B1 2,3-oxide as a major electrophilic metabolite of aflatoxin B1 in rat and hamster liver microsomal systems, since this highly reactive epoxide would be expected to hydrolyze readily to form the dihydrodiol.", "contents": "Reduced nicotinamide adenine dinucleotide phosphate-dependent formation of 2,3-dihydro-2,3-dihydroxyaflatoxin B1 from aflatoxin B1 by hepatic microsomes. 2,3-Dihydro-2,3-dihydroxyaflatoxin B1 (dihydrodiol) was formed as a major metabolite in the incubation of aflatoxin B1 with rat and hamster liver microsomes. The yield of the dihydrodiol was maximal at pH 6.5, was reduced nicotinmide adenine dinucleotide phosphate- and cytochrome P-450-dependent, and was increased 2- to 4-fold by pretreatment of the animals with phenobarbital; pretreatment with 3-methylcholanthrene did not alter the activity of rat hepatic microsomes. Inhibitors of epoxide hydrase did not lower the yield of the dihydrodiol in these systems. Negligible yields of the dihydrodiol were formed from aflatoxin B1 and rat liver microsomes in the presence of DNA. Little or no formation of the dihydrodiol was noted with microsomes from rat intestinal mucosa, kidney, or lung. These results further support the formation of aflatoxin B1 2,3-oxide as a major electrophilic metabolite of aflatoxin B1 in rat and hamster liver microsomal systems, since this highly reactive epoxide would be expected to hydrolyze readily to form the dihydrodiol."}
{"id": "PMID:27304", "title": "Quantitative characteristics of the Feyrter cells and neuroepithelial bodies of the fetal rabbit lung in normoxia and short term chronic hypoxia.", "content": "We report here quantitative data on the Feyrter (single) cells (APUD cells) and neuroepithelial bodies (grouped Feyrter cells), in the lungs of rabbit fetuses at 26, 27.5 and 29 days gestational age, during normoxia and short term chronic hypoxia. The apparent number of these cells declines during this period; we suggest that this might be due to increased hypoxemia. Moreover, the number of cells in the lungs of fetuses from short term chronically hypoxic mothers is lower than in the normoxic animals. These findings are in agreement with our previous studies in short term chronically hypoxic neonatal rabbits, and suggest that the increased hypoxemia in the fetus, caused by the induction of hypoxia in the mother, constitutes a stimulus for secretory activity of the Feyrter cells and neuroepithelial bodies (NEBs). This in turn could be part of the mechanism responsible for maintaining the pulmonary vasoconstriction due to hypoxemia. Our results from fetuses of normoxic does provide base line data on the chronological importance of the Feyrter cells and NEBs.", "contents": "Quantitative characteristics of the Feyrter cells and neuroepithelial bodies of the fetal rabbit lung in normoxia and short term chronic hypoxia. We report here quantitative data on the Feyrter (single) cells (APUD cells) and neuroepithelial bodies (grouped Feyrter cells), in the lungs of rabbit fetuses at 26, 27.5 and 29 days gestational age, during normoxia and short term chronic hypoxia. The apparent number of these cells declines during this period; we suggest that this might be due to increased hypoxemia. Moreover, the number of cells in the lungs of fetuses from short term chronically hypoxic mothers is lower than in the normoxic animals. These findings are in agreement with our previous studies in short term chronically hypoxic neonatal rabbits, and suggest that the increased hypoxemia in the fetus, caused by the induction of hypoxia in the mother, constitutes a stimulus for secretory activity of the Feyrter cells and neuroepithelial bodies (NEBs). This in turn could be part of the mechanism responsible for maintaining the pulmonary vasoconstriction due to hypoxemia. Our results from fetuses of normoxic does provide base line data on the chronological importance of the Feyrter cells and NEBs."}
{"id": "PMID:27305", "title": "pH-dependent behaviour of erythrocyte membrane elevations.", "content": "Freeze-etch electron microscopy of human erythrocytes from heparinized normal blood reveals membrane elevations. These elevations disappear at low pH values and reappear under normal pH conditions in vitro, both in the absence and the presence of plasma. This pH-dependent behaviour is discussed as an intrinsic membrane event.", "contents": "pH-dependent behaviour of erythrocyte membrane elevations. Freeze-etch electron microscopy of human erythrocytes from heparinized normal blood reveals membrane elevations. These elevations disappear at low pH values and reappear under normal pH conditions in vitro, both in the absence and the presence of plasma. This pH-dependent behaviour is discussed as an intrinsic membrane event."}
{"id": "PMID:27306", "title": "Kinetic studies on the interaction of gold (III) with nucleic acids. IV. RNA-Au (III) system.", "content": "The kinetics of the interaction of Au(III) with whole yeast RNA has been studied using UV-spectrophotometry. The reaction is second order with respect to the nucleotide unit of RNA and first order with respect to Au(III) in the respective stoichiometry of 2 : 1. The effects of initial composition, temperature, ionic strength, pH and chloride ion on the kinetics have been studied. Activation energy is found to be 11.5 kcal/mol. Effect of ionic strength indicates that both the positively charged and neutral species of Au(III) take part in the rate limiting step, the former being dominant at low ionic strength. A plausible mechanism has been proposed which involves the interaction of two nucleotide units of RNA with one species of Au(III) in the rate limiting step.", "contents": "Kinetic studies on the interaction of gold (III) with nucleic acids. IV. RNA-Au (III) system. The kinetics of the interaction of Au(III) with whole yeast RNA has been studied using UV-spectrophotometry. The reaction is second order with respect to the nucleotide unit of RNA and first order with respect to Au(III) in the respective stoichiometry of 2 : 1. The effects of initial composition, temperature, ionic strength, pH and chloride ion on the kinetics have been studied. Activation energy is found to be 11.5 kcal/mol. Effect of ionic strength indicates that both the positively charged and neutral species of Au(III) take part in the rate limiting step, the former being dominant at low ionic strength. A plausible mechanism has been proposed which involves the interaction of two nucleotide units of RNA with one species of Au(III) in the rate limiting step."}
{"id": "PMID:27308", "title": "[Culicidae of the French Territory of Afars and Issas. The genera Aedes, Culiseta, Uranotaenia and Mimomyia].", "content": "During an entomological survey conducted in French Territory of Afars and Issas from november 1973 to june 1975, the following species were collected: Aedes caspius, A. vittatus, Culiseta longeareolata, Uranotaenia balfouri, Mimomyia mimomyiaformis, M. mediolineata. To these mosquitoes, we must add the record of A. aegypti larvae on a dhow berthing in Djibuti while this mosquito does not exist actually in the Territory. The epidemiological importance of these culicids is discussed.", "contents": "[Culicidae of the French Territory of Afars and Issas. The genera Aedes, Culiseta, Uranotaenia and Mimomyia]. During an entomological survey conducted in French Territory of Afars and Issas from november 1973 to june 1975, the following species were collected: Aedes caspius, A. vittatus, Culiseta longeareolata, Uranotaenia balfouri, Mimomyia mimomyiaformis, M. mediolineata. To these mosquitoes, we must add the record of A. aegypti larvae on a dhow berthing in Djibuti while this mosquito does not exist actually in the Territory. The epidemiological importance of these culicids is discussed."}
{"id": "PMID:27313", "title": "[Pharmacological study of para-aminoclonidine, an alpha sympathomimetic].", "content": "Para-aminoclonidine is a more potent alpha-adrenergic agent than clonidine; in vitro on Rat aorta it is 150 times more active than NE, in vivo on pithed Rat it is still twice as active. The hypotensive action of paraaminoclondine is only manifested when given intraventricularly. In the conscious Rat, it has a diuretic action when given per os. Following IV injection in the anaesthetized Dog, the para-aminoclonidine induces an essentially hydric diuresis which is independet of its hypertensive action.", "contents": "[Pharmacological study of para-aminoclonidine, an alpha sympathomimetic]. Para-aminoclonidine is a more potent alpha-adrenergic agent than clonidine; in vitro on Rat aorta it is 150 times more active than NE, in vivo on pithed Rat it is still twice as active. The hypotensive action of paraaminoclondine is only manifested when given intraventricularly. In the conscious Rat, it has a diuretic action when given per os. Following IV injection in the anaesthetized Dog, the para-aminoclonidine induces an essentially hydric diuresis which is independet of its hypertensive action."}
{"id": "PMID:27309", "title": "[Significance of the various toxins present on dead coral substrata in the origin of ciguatera].", "content": "The authors look directly on the coral reefs the toxins carried by poisonous fish. Pointing out two major toxic substances, they discuss their respective role in ciguatera physiopathology and suggest a new hypothesis for the origin of the phenomenon.", "contents": "[Significance of the various toxins present on dead coral substrata in the origin of ciguatera]. The authors look directly on the coral reefs the toxins carried by poisonous fish. Pointing out two major toxic substances, they discuss their respective role in ciguatera physiopathology and suggest a new hypothesis for the origin of the phenomenon."}
{"id": "PMID:27314", "title": "[Respiratory function of blood and relative weight of certain organs in two species of shrew: Crocidura russula and Suncus etruscus (Soricidae mammals)].", "content": "A high oxygen capacity combined with a low oxygen affinity and a large Bohr effect achieve a high oxygen transport capacity in small shrews. The high metabolic rate (Suncus estruscus: 100 to 350 ml O2/kg. min) can be explained by the combination of the favorable blood parameters with a high relative heart weight (1,2% of body weight) and heart frequencies of 1,000 to 1,350 per minute.", "contents": "[Respiratory function of blood and relative weight of certain organs in two species of shrew: Crocidura russula and Suncus etruscus (Soricidae mammals)]. A high oxygen capacity combined with a low oxygen affinity and a large Bohr effect achieve a high oxygen transport capacity in small shrews. The high metabolic rate (Suncus estruscus: 100 to 350 ml O2/kg. min) can be explained by the combination of the favorable blood parameters with a high relative heart weight (1,2% of body weight) and heart frequencies of 1,000 to 1,350 per minute."}
{"id": "PMID:27310", "title": "[Examination of the enzymatic functions of the normal liver in black Africans (Apropos of 50 Senegalese cases)].", "content": "In order to establish the hepatic enzymogram in healthy African black people, four enzymes have been studied in 50 apparently healthy male Africans: transaminases (GOT, GPT), alcaline phosphatases, ornithine carbamoyltransferase (OCT) and gamma-glutamyl transpeptidase (GGT). The findings do not show any difference with the usually admitted levels in European countries, except for alcaline phosphatases which are situated at the upper limit of the normal.", "contents": "[Examination of the enzymatic functions of the normal liver in black Africans (Apropos of 50 Senegalese cases)]. In order to establish the hepatic enzymogram in healthy African black people, four enzymes have been studied in 50 apparently healthy male Africans: transaminases (GOT, GPT), alcaline phosphatases, ornithine carbamoyltransferase (OCT) and gamma-glutamyl transpeptidase (GGT). The findings do not show any difference with the usually admitted levels in European countries, except for alcaline phosphatases which are situated at the upper limit of the normal."}
{"id": "PMID:27315", "title": "[Effect of total and prolonged starvation on the acid soluble nucleotides in carp liver].", "content": "The composition of the acid soluble nucleotide pool of Carp liver was determined by column chromatography, and its changes were followed during prolonged total fast. Total prolonged starvation caused substantial changes in the distribution of hepatocyte free nucleotides. Eleven months of starvation caused a reduction in the concentration of di- and triphosphate nucleosides as well as a diminution of the oxido-reduction of the hepatocyte. Only pyrimidine nucleoside monophosphates remained at concentration approaching those found in regularly fed Carp.", "contents": "[Effect of total and prolonged starvation on the acid soluble nucleotides in carp liver]. The composition of the acid soluble nucleotide pool of Carp liver was determined by column chromatography, and its changes were followed during prolonged total fast. Total prolonged starvation caused substantial changes in the distribution of hepatocyte free nucleotides. Eleven months of starvation caused a reduction in the concentration of di- and triphosphate nucleosides as well as a diminution of the oxido-reduction of the hepatocyte. Only pyrimidine nucleoside monophosphates remained at concentration approaching those found in regularly fed Carp."}
{"id": "PMID:27316", "title": "[Modification of the effect of cardio-accelerator nerve stimulation in dogs by clonidine and several alpha-adrenolytics].", "content": "In dogs anaesthetized with pentobarbital (30 mg. kg -1 i.v.), clonidine (0,01 mg.kg-1 i.v.) reduced the tachycardia induced at low frequencies by stimulation of the cardiac nerve. The effects of some alpha-adrenoceptor blocking agents on this effect have been studied. Small doses of yohimbine (0.3 mg. kg-1 i.v.) or piperoxan (0.3 mg. kg-1 i.v.) increased the effects of the stimulation and in addition antagonized the inhibitory effects of clonidine and reversed the pressor response to adrenaline. Thymoxamine (1 mg.kg-1 i.v.) and prazosin (1 mg.kg-1 i.v.) did not increase the effect of the stimulation of the cardiac nerve, but reduced the effect of clonidine. ARC239 (0.05 mg.kg-1) reversed the pressor response to adrenaline but even at high doses did not increase the effects of the stimulation of the cardiac nerve or the effects of clonidine. These observations afford further evidence for a dissimilarity between pre and post-synaptic alpha-adrenoceptors.", "contents": "[Modification of the effect of cardio-accelerator nerve stimulation in dogs by clonidine and several alpha-adrenolytics]. In dogs anaesthetized with pentobarbital (30 mg. kg -1 i.v.), clonidine (0,01 mg.kg-1 i.v.) reduced the tachycardia induced at low frequencies by stimulation of the cardiac nerve. The effects of some alpha-adrenoceptor blocking agents on this effect have been studied. Small doses of yohimbine (0.3 mg. kg-1 i.v.) or piperoxan (0.3 mg. kg-1 i.v.) increased the effects of the stimulation and in addition antagonized the inhibitory effects of clonidine and reversed the pressor response to adrenaline. Thymoxamine (1 mg.kg-1 i.v.) and prazosin (1 mg.kg-1 i.v.) did not increase the effect of the stimulation of the cardiac nerve, but reduced the effect of clonidine. ARC239 (0.05 mg.kg-1) reversed the pressor response to adrenaline but even at high doses did not increase the effects of the stimulation of the cardiac nerve or the effects of clonidine. These observations afford further evidence for a dissimilarity between pre and post-synaptic alpha-adrenoceptors."}
{"id": "PMID:27317", "title": "[Changes in the distribution of gamma-glutamyl transferase in the organs of the mouse as a function of development].", "content": "In the Mouse, gamma-glutamyl transferase distribution changes with development in the kidney and the liver; on the contrary, its activity remains almost equal and low in other organs. In the liver, a low activity is observed in the fetus and the new-born up to the 3rd day of life; then it is no more measurable. In the kidney, the low enzyme activity of the fetus is multiplied by 10 in the 10 first days of life and by 50 in the 6 first weeks.", "contents": "[Changes in the distribution of gamma-glutamyl transferase in the organs of the mouse as a function of development]. In the Mouse, gamma-glutamyl transferase distribution changes with development in the kidney and the liver; on the contrary, its activity remains almost equal and low in other organs. In the liver, a low activity is observed in the fetus and the new-born up to the 3rd day of life; then it is no more measurable. In the kidney, the low enzyme activity of the fetus is multiplied by 10 in the 10 first days of life and by 50 in the 6 first weeks."}
{"id": "PMID:27318", "title": "[Comparative action of toxins isolated from the venom of the scorpion (Androctonus australis) and the tentacles of the sea anemone (Anemonia Sulcata) on an isolated frog neuromuscular preparation].", "content": "We have shown that, if Scorpion venom is acting a skeletal muscle indirectly by releasing Acetycholine and directly by inducing an increase in intracellular free calcium, the main action of toxin II isolated from Anemonia Sulcata tentacles is presynaptic.", "contents": "[Comparative action of toxins isolated from the venom of the scorpion (Androctonus australis) and the tentacles of the sea anemone (Anemonia Sulcata) on an isolated frog neuromuscular preparation]. We have shown that, if Scorpion venom is acting a skeletal muscle indirectly by releasing Acetycholine and directly by inducing an increase in intracellular free calcium, the main action of toxin II isolated from Anemonia Sulcata tentacles is presynaptic."}
{"id": "PMID:27319", "title": "[Action of toxin II isolated from the tentacles of sea anemones on the neuromuscular transmission on normal and botulin toxin inhibited frogs].", "content": "In our experimental conditions, toxin II from Anemonia sulcata restored Frog neuromuscular transmission blocked by botulinum toxin, type A.", "contents": "[Action of toxin II isolated from the tentacles of sea anemones on the neuromuscular transmission on normal and botulin toxin inhibited frogs]. In our experimental conditions, toxin II from Anemonia sulcata restored Frog neuromuscular transmission blocked by botulinum toxin, type A."}
{"id": "PMID:27322", "title": "Observations on serum and urine alkaline ribonuclease activity and urate after burn injury in man.", "content": "In an investigation into the disturbances of body function associated with burn injury we have measured the activity of alkaline ribonuclease (EC 3.1.4.22) and the level of urate in the serum and urine of patients sustaining burn injury. Ribonuclease activity was elevated in all patients. The degree of elevation can be related to the percentage of the body surface area burned and to a predictive index of burn mortality. Increased serum ribonuclease activity was accompanied by increased urine ribonuclease output. The relationship between serum urea and ribonuclease activity has been investigated. A significant correlation between these two parameters was observed during the first week post burn. We suggest that this correlation shows as a result of increased protein catabolism and renal dysfunction. After the first week a significant correlation between serum urea and ribonuclease activity was not observed. It is possible that, at this stage, increased ribonuclease activity is perhaps a result of tissue repair. Serum urate was found to be decreased in all patients after burn injury. Serum urate decrease expressed as a percentage of initial value, correlated very strongly with the predictive index of burn mortality. In severely burned patients the decrease in serum urate was accompanied by increased urine urate output and may indicate a change in renal handling of urate after burn injury.", "contents": "Observations on serum and urine alkaline ribonuclease activity and urate after burn injury in man. In an investigation into the disturbances of body function associated with burn injury we have measured the activity of alkaline ribonuclease (EC 3.1.4.22) and the level of urate in the serum and urine of patients sustaining burn injury. Ribonuclease activity was elevated in all patients. The degree of elevation can be related to the percentage of the body surface area burned and to a predictive index of burn mortality. Increased serum ribonuclease activity was accompanied by increased urine ribonuclease output. The relationship between serum urea and ribonuclease activity has been investigated. A significant correlation between these two parameters was observed during the first week post burn. We suggest that this correlation shows as a result of increased protein catabolism and renal dysfunction. After the first week a significant correlation between serum urea and ribonuclease activity was not observed. It is possible that, at this stage, increased ribonuclease activity is perhaps a result of tissue repair. Serum urate was found to be decreased in all patients after burn injury. Serum urate decrease expressed as a percentage of initial value, correlated very strongly with the predictive index of burn mortality. In severely burned patients the decrease in serum urate was accompanied by increased urine urate output and may indicate a change in renal handling of urate after burn injury."}
{"id": "PMID:27323", "title": "Some pitfalls in the quality control of alkaline phosphatase activity.", "content": "A study of the pH optimum of alkaline phosphatase activity in calibration and control serum preparations reveals a wide variation in pH optima. It is shown that as small an error of +/- 0.05 pH units in preparation of the buffered substrate results in an error in the order of +/- 5% in the response between the calibrating serum and patient specimens. It is recommended that a calibration serum should closely parallel the pH optimum of alkaline phosphatase in human sera and that a quality control serum containing alkaline phosphatase of alternative source to that present in the calibration serum be included with patient samples as a sensitive means of monitoring pH changes in the buffered substrate.", "contents": "Some pitfalls in the quality control of alkaline phosphatase activity. A study of the pH optimum of alkaline phosphatase activity in calibration and control serum preparations reveals a wide variation in pH optima. It is shown that as small an error of +/- 0.05 pH units in preparation of the buffered substrate results in an error in the order of +/- 5% in the response between the calibrating serum and patient specimens. It is recommended that a calibration serum should closely parallel the pH optimum of alkaline phosphatase in human sera and that a quality control serum containing alkaline phosphatase of alternative source to that present in the calibration serum be included with patient samples as a sensitive means of monitoring pH changes in the buffered substrate."}
{"id": "PMID:27327", "title": "Characterization of beta-adrenergic receptor linked to adenylate cyclase in a human cancer cell line (COLO 16).", "content": "1. A human cancer cell line (COLO 16) derived originally from an epidermal squamous cell carcinoma was found to possess adenylate cyclase responsiveness to beta-adrenergic agonists. 2. The adenylate cyclase response was characterized with respect to activation constants (KA) for various beta-adrenergic agonists and inhibition constants (Ki) for antagonists. 3. Intact cells responded with dose-dependent increases in production of cyclic adenosine 3':5'-monophosphate. 4. Properties of the beta-adrenergic receptor were evaluated by using the specific binding of [3H]propranolol to cell membranes. Specific binding was saturable, with KD 5.79 nmol/l and binding sites 0.68 pmol/mg of protein. 5. Competition for binding to cell membranes was shown by beta-adrenergic agonists and antagonists and was stereospecific. There was close agreement between the affinity of these various agents on adenylate cyclase and receptor binding. 6. It is likely that the beta-adrenergic receptor-linked adenylate cyclase in COLO 16 cells represents persistence in a cancer cell line of a receptor present normally in epidermal cells.", "contents": "Characterization of beta-adrenergic receptor linked to adenylate cyclase in a human cancer cell line (COLO 16). 1. A human cancer cell line (COLO 16) derived originally from an epidermal squamous cell carcinoma was found to possess adenylate cyclase responsiveness to beta-adrenergic agonists. 2. The adenylate cyclase response was characterized with respect to activation constants (KA) for various beta-adrenergic agonists and inhibition constants (Ki) for antagonists. 3. Intact cells responded with dose-dependent increases in production of cyclic adenosine 3':5'-monophosphate. 4. Properties of the beta-adrenergic receptor were evaluated by using the specific binding of [3H]propranolol to cell membranes. Specific binding was saturable, with KD 5.79 nmol/l and binding sites 0.68 pmol/mg of protein. 5. Competition for binding to cell membranes was shown by beta-adrenergic agonists and antagonists and was stereospecific. There was close agreement between the affinity of these various agents on adenylate cyclase and receptor binding. 6. It is likely that the beta-adrenergic receptor-linked adenylate cyclase in COLO 16 cells represents persistence in a cancer cell line of a receptor present normally in epidermal cells."}
{"id": "PMID:27328", "title": "The nature of inactive renin in human plasma and amniotic fluid.", "content": "1. The properties of inactive and active renin in human plasma and amniotic fluid were studied chromatographically. Activation was achieved at pH 3.3 with and without added pepsin. 2. Acid activation of renin was time- and temperature-dependent but was inhibited by dilution of the sample. The dilution effect was corrected by adding pepsin. Such characteristics indicate that activation at low pH is catalysed by intrinsic enzymes. 3. Separation and/or dilution of the activating enzyme during ion-exchange chromatography concealed the eluted position of inactive renin and reduced the amount recovered. Only after full activation of the eluted renin was achieved with added pepsin was a distinct peak of inactive renin exposed. 4. At pH 7.5 inactive renin carried a lower negative charge than the active enzyme. This charge difference was lost after activation. 5. No molecular-weight differences between active, inactive renin or the International Renin Standard were detected by gel filtration. No renin of larger molecular weight was present. 6. These findings will be helpful in purification studies of human inactive renin.", "contents": "The nature of inactive renin in human plasma and amniotic fluid. 1. The properties of inactive and active renin in human plasma and amniotic fluid were studied chromatographically. Activation was achieved at pH 3.3 with and without added pepsin. 2. Acid activation of renin was time- and temperature-dependent but was inhibited by dilution of the sample. The dilution effect was corrected by adding pepsin. Such characteristics indicate that activation at low pH is catalysed by intrinsic enzymes. 3. Separation and/or dilution of the activating enzyme during ion-exchange chromatography concealed the eluted position of inactive renin and reduced the amount recovered. Only after full activation of the eluted renin was achieved with added pepsin was a distinct peak of inactive renin exposed. 4. At pH 7.5 inactive renin carried a lower negative charge than the active enzyme. This charge difference was lost after activation. 5. No molecular-weight differences between active, inactive renin or the International Renin Standard were detected by gel filtration. No renin of larger molecular weight was present. 6. These findings will be helpful in purification studies of human inactive renin."}
{"id": "PMID:27331", "title": "Immunologically mediated drug-induced acute renal failure.", "content": "(1) AIN is the most frequent pattern of drug-induced immunologically mediated renal injury. A number of drugs may be responsible for AIN, namely methicillin and other penicillin derivatives, rifampicin, phenindione and sulfonamides. Particular clinical and pathological features often suggest an immune pathogenetic mechanism. IgG anti-TBM and IgE antibodies have been found in only a few cases and it is likely that antibody-mediated and cell-mediated injury may operate in the same patient. (2) Only few examples of drug-induced vasculitis and glomerulonephritis are known, and the pathophysiology of this kind of renal damage is poorly understood.", "contents": "Immunologically mediated drug-induced acute renal failure. (1) AIN is the most frequent pattern of drug-induced immunologically mediated renal injury. A number of drugs may be responsible for AIN, namely methicillin and other penicillin derivatives, rifampicin, phenindione and sulfonamides. Particular clinical and pathological features often suggest an immune pathogenetic mechanism. IgG anti-TBM and IgE antibodies have been found in only a few cases and it is likely that antibody-mediated and cell-mediated injury may operate in the same patient. (2) Only few examples of drug-induced vasculitis and glomerulonephritis are known, and the pathophysiology of this kind of renal damage is poorly understood."}
{"id": "PMID:27337", "title": "Coupling of cerebral metabolism and blood flow in epileptic seizures, hypoxia and hypoglycaemia.", "content": "This study examines the possibility that changes of cerebral extracellular pH (PH e) or adenosine concentration may provide coupling mechanisms of a general nautre, adjusting cerebral blood flow (CBF) to metabolic demands. Although there is considerable indirect evidence that CBF varies inversely with pHe, results obtained during the last few years indicate that large increases in flow may occur in the absence of a fall in pHe. Thus, induction of hypoxia or epileptic seizures leads to maximal increase in CBF before pHe falls or even when there is initial alkalosis due to concomitant hypocapnia. Furthermore, CBF increases in hypoglycaemia and after administration of amphetamine, two conditions unassociated with tissue acidosis. The possibility that adenosine may be a coupling factor was examined in hypoxia and during epileptic seizures in rats. In both conditions a four- to fivefold increase in CBF occurs in spite of the fact that tissue adenosine concentrations remain at or below 1 mumolkg-u. It is concluded that adenosine accumulates first when there is a perturbation of cerebral energy state with a rise in AMP concentration. It seems unlikely that adenosine, formed by breakdown of AMP, acts as a general coupling factor.", "contents": "Coupling of cerebral metabolism and blood flow in epileptic seizures, hypoxia and hypoglycaemia. This study examines the possibility that changes of cerebral extracellular pH (PH e) or adenosine concentration may provide coupling mechanisms of a general nautre, adjusting cerebral blood flow (CBF) to metabolic demands. Although there is considerable indirect evidence that CBF varies inversely with pHe, results obtained during the last few years indicate that large increases in flow may occur in the absence of a fall in pHe. Thus, induction of hypoxia or epileptic seizures leads to maximal increase in CBF before pHe falls or even when there is initial alkalosis due to concomitant hypocapnia. Furthermore, CBF increases in hypoglycaemia and after administration of amphetamine, two conditions unassociated with tissue acidosis. The possibility that adenosine may be a coupling factor was examined in hypoxia and during epileptic seizures in rats. In both conditions a four- to fivefold increase in CBF occurs in spite of the fact that tissue adenosine concentrations remain at or below 1 mumolkg-u. It is concluded that adenosine accumulates first when there is a perturbation of cerebral energy state with a rise in AMP concentration. It seems unlikely that adenosine, formed by breakdown of AMP, acts as a general coupling factor."}
{"id": "PMID:27339", "title": "Control of cerebral vascular smooth muscle during general anaesthesia.", "content": "The effects of some general anaesthetics, for example thiopentone, Althesin (alphaxalone + alphadolone) and ketamine, on cerebral vascular smooth muscle are those which would be expected from their metabolic actions. With other anaesthetics, mainly those administered by inhalation, and especially the volatile agents, cerebral blood flow increases in excess of the metabolic activity, which is usually depressed to varying degrees. During general anaesthesia with any of these agents, responses to changes in arterial Pco2 or blood pressure are maintained. Furthermore, when seizure activity occurs during enflurane administration, there is a flow response to the associated metabolic stimulation. The time course of the flow response to the metabolically depressant drug Althesin has been measured in baboons and shown to be very rapid. Wtih this drug cerebrovascular resistance begins to increase within 2 s of its arrival in the brain. This rapid flow change occurs also after sympathetic denervation. Extracellular fluid pH of the cortex does not alter until after the initiation of the vascular smooth muscle response.", "contents": "Control of cerebral vascular smooth muscle during general anaesthesia. The effects of some general anaesthetics, for example thiopentone, Althesin (alphaxalone + alphadolone) and ketamine, on cerebral vascular smooth muscle are those which would be expected from their metabolic actions. With other anaesthetics, mainly those administered by inhalation, and especially the volatile agents, cerebral blood flow increases in excess of the metabolic activity, which is usually depressed to varying degrees. During general anaesthesia with any of these agents, responses to changes in arterial Pco2 or blood pressure are maintained. Furthermore, when seizure activity occurs during enflurane administration, there is a flow response to the associated metabolic stimulation. The time course of the flow response to the metabolically depressant drug Althesin has been measured in baboons and shown to be very rapid. Wtih this drug cerebrovascular resistance begins to increase within 2 s of its arrival in the brain. This rapid flow change occurs also after sympathetic denervation. Extracellular fluid pH of the cortex does not alter until after the initiation of the vascular smooth muscle response."}
{"id": "PMID:27343", "title": "Production, metabolism and possible functions of adenosine in brain tissue in situ.", "content": "Adenosine and H+ may act synergistically to regulate cerebral blood flow because adenosine production is enhanced under various experimental conditions associated with an imbalance between oxygen supply and oxygen need. Direct application of adenosine dilates the pial vessels, but changes in cerebral vascular resistance are not observed when adenosine is infused intraarterially. This is because adenosine does not readily cross the blood-brain barrier. The studies reported here show that in dogs the adenosine released into the interstitium is partly reincorporated into adenine nucleotides via an adenosine kinase (EC 2.7.1.20) reaction (salvage pathway) and partly degraded to inosine and hypoxanthine. However, in contrast to other tissues, the accumulation of iosine and hypoxanthine in brain tissue proceeds at a rate slower than that of adenosine because one of the degradative enzymes, namely purine-nucleoside phosphorylase (EC 2.4.2.1) is located only in the vessel wall, which is not readily permeable to adenosine. Thus, the slow access of adenosine to its degradative enzymes delays the appearance of its products, inosine and hypoxanthine.", "contents": "Production, metabolism and possible functions of adenosine in brain tissue in situ. Adenosine and H+ may act synergistically to regulate cerebral blood flow because adenosine production is enhanced under various experimental conditions associated with an imbalance between oxygen supply and oxygen need. Direct application of adenosine dilates the pial vessels, but changes in cerebral vascular resistance are not observed when adenosine is infused intraarterially. This is because adenosine does not readily cross the blood-brain barrier. The studies reported here show that in dogs the adenosine released into the interstitium is partly reincorporated into adenine nucleotides via an adenosine kinase (EC 2.7.1.20) reaction (salvage pathway) and partly degraded to inosine and hypoxanthine. However, in contrast to other tissues, the accumulation of iosine and hypoxanthine in brain tissue proceeds at a rate slower than that of adenosine because one of the degradative enzymes, namely purine-nucleoside phosphorylase (EC 2.4.2.1) is located only in the vessel wall, which is not readily permeable to adenosine. Thus, the slow access of adenosine to its degradative enzymes delays the appearance of its products, inosine and hypoxanthine."}
{"id": "PMID:27344", "title": "Cellular microenvironment in relation to local blood flow.", "content": "The investigation was designed to identify microenvironmental factors that might be important in the regulation of local blood flow. Cellular microenvironment in terms of Po2, pH, [K+], [Cl-], [Ca2+] and lactate was measured in rat brain by means of specific microelectrodes. Vascular endothelium was stained in vivo with Thioflavine S. Local blood flow was measured with micro hydrogen electrodes. Some intracellular measurements of pH were made in conjunction with extracellular measurements. The main findings were that local autoregulation responses and blood flow changes in response to imposed hypoxic changes were very rapid (1-1.5 s). Microflow responses to changes in local cell activity were limited to a region not more than 250 micron in diameter. Increased blood flow in acute hypoxia occurred within 1-2 s of the fall in tissue Po2 and was much more rapid than changes in either pH or potassium. Intracellular pH changed within 10 s of the onset of severe hypoxia but in all cases the blood flow followed the Po2 much more closely than any other parameter. It is suggested that changes in capillary endothelium and local membrane transmission may play a part in autoregulatory mechanisms.", "contents": "Cellular microenvironment in relation to local blood flow. The investigation was designed to identify microenvironmental factors that might be important in the regulation of local blood flow. Cellular microenvironment in terms of Po2, pH, [K+], [Cl-], [Ca2+] and lactate was measured in rat brain by means of specific microelectrodes. Vascular endothelium was stained in vivo with Thioflavine S. Local blood flow was measured with micro hydrogen electrodes. Some intracellular measurements of pH were made in conjunction with extracellular measurements. The main findings were that local autoregulation responses and blood flow changes in response to imposed hypoxic changes were very rapid (1-1.5 s). Microflow responses to changes in local cell activity were limited to a region not more than 250 micron in diameter. Increased blood flow in acute hypoxia occurred within 1-2 s of the fall in tissue Po2 and was much more rapid than changes in either pH or potassium. Intracellular pH changed within 10 s of the onset of severe hypoxia but in all cases the blood flow followed the Po2 much more closely than any other parameter. It is suggested that changes in capillary endothelium and local membrane transmission may play a part in autoregulatory mechanisms."}
{"id": "PMID:27346", "title": "[Diethylpentenamide, a substitute for carbromal? (author's transl)].", "content": "Bromcarbamide-containing sleeping pills are frequently used in suicide attempts and cause severe, often fatal, intoxication. Since 1975, the chemically related drug diethylpentenamide had been available (in the German Federal Republic) without prescription. The authors report four cases of attempted suicide with the drug. The signs were similar to those after carbromal intoxication. There was severe respiratory depression, successfully treated by extracorporeal detoxication with combined haemoperfusion and haemodialysis. One patient developed acute pancreatitis as a complication.", "contents": "[Diethylpentenamide, a substitute for carbromal? (author's transl)]. Bromcarbamide-containing sleeping pills are frequently used in suicide attempts and cause severe, often fatal, intoxication. Since 1975, the chemically related drug diethylpentenamide had been available (in the German Federal Republic) without prescription. The authors report four cases of attempted suicide with the drug. The signs were similar to those after carbromal intoxication. There was severe respiratory depression, successfully treated by extracorporeal detoxication with combined haemoperfusion and haemodialysis. One patient developed acute pancreatitis as a complication."}
{"id": "PMID:27347", "title": "[Salazosulfapyridine-induced lupus erythematosus syndrome in ulcerative colitis (author's transl)].", "content": "In a 25-year old woman with ulcerative colitis a lupus erythematosus syndrome occurred during treatment with salazosulfapyridine. The connection with medication was ascertained by reexposition. Some of the systemic complications of ulcerative colitis may possibly be due to the salazosulfapyridine medication.", "contents": "[Salazosulfapyridine-induced lupus erythematosus syndrome in ulcerative colitis (author's transl)]. In a 25-year old woman with ulcerative colitis a lupus erythematosus syndrome occurred during treatment with salazosulfapyridine. The connection with medication was ascertained by reexposition. Some of the systemic complications of ulcerative colitis may possibly be due to the salazosulfapyridine medication."}
{"id": "PMID:27348", "title": "Pharmacological study of cholinergic mechanisms of compensatory ovarian hypertrophy in rats.", "content": "Treatment of hemicastrated adult female rats with nicotine increased the compensatory ovarian hypertrophy (COH) while central n-cholinolytic IEM-506 decreased COH and prevented the estrogen-induced suppression of COH. Administration of L-DOPA abolished the effect of IEM-506, and disulfiram blocked gonadotropic action of nicotine. Elevation of the dose of arecoline decreased COH and the sensitivity of hypothalamo-gonadotropic complex to estrogen suppression. Treatment of rats with L-DOPA and disulfiram abolished the late effect of arecoline. Central m-cholinolytic metamizyl decreased COH, potentiated the effect of estrogen and prevented the gonadotropic effect of L-DOPA. The regulatory role of m-cholinergic systems in noradrenaline mediation of gonadotropic function and n-cholinergic system in dopamine ones are suggested.", "contents": "Pharmacological study of cholinergic mechanisms of compensatory ovarian hypertrophy in rats. Treatment of hemicastrated adult female rats with nicotine increased the compensatory ovarian hypertrophy (COH) while central n-cholinolytic IEM-506 decreased COH and prevented the estrogen-induced suppression of COH. Administration of L-DOPA abolished the effect of IEM-506, and disulfiram blocked gonadotropic action of nicotine. Elevation of the dose of arecoline decreased COH and the sensitivity of hypothalamo-gonadotropic complex to estrogen suppression. Treatment of rats with L-DOPA and disulfiram abolished the late effect of arecoline. Central m-cholinolytic metamizyl decreased COH, potentiated the effect of estrogen and prevented the gonadotropic effect of L-DOPA. The regulatory role of m-cholinergic systems in noradrenaline mediation of gonadotropic function and n-cholinergic system in dopamine ones are suggested."}
{"id": "PMID:27353", "title": "The stimulus-secretion coupling of glucose-induced insulin release. Metabolic effects of menadione in isolated islets.", "content": "Pancreatic islets contain an enzyme system which catalyzes the donation of hydrogen from NAD(P)H to menadione (2-methyl-1,4-naphthoquinone). In high concentrations (20 to 50 micrometer), menadione, in addition to lowering the concentration of reduced pyridine nucleotides in the islets, also impairs glycolysis and glucose oxidation, decreases ATP concentration, and inhibits proinsulin biosynthesis. However, at a 10 micrometer concentration, menadione fails to affect the concentration of adenine nucleotides, the utilization of glucose, the production of lactate and pyruvate, the oxidation of [6-14C]glucose and the synthesis of proinsulin; whereas the metabolism of glucose through the pentose shunt is markedly increased. The sole inhibitory effect of menadione 10 micrometer upon metabolic parameters is to reduce the concentration of both NADH and NADPH, such an effect being noticed in islets exposed to glucose 11.1 mM but not in those incubated at a higher glucose level (27.8 mM). Since, in the presence of glucose 11.1 mM, menadione 10 micrometer also severely decreases glucose-stimulated45 calcium net uptake and subsequent insulin release, it is concluded that the availability of reduced pyridine nucleotides may play an essential role in the secretory sequence by coupling metabolic to cationic events. Thus, when insulinotropic nutrients are oxidized in the B-cell, the increased availability of reduced pyridine nucleotides could modify the affinity for cations of native ionophoretic systems, eventually leading to the accumulation of calcium up to a level sufficient to trigger insulin release.", "contents": "The stimulus-secretion coupling of glucose-induced insulin release. Metabolic effects of menadione in isolated islets. Pancreatic islets contain an enzyme system which catalyzes the donation of hydrogen from NAD(P)H to menadione (2-methyl-1,4-naphthoquinone). In high concentrations (20 to 50 micrometer), menadione, in addition to lowering the concentration of reduced pyridine nucleotides in the islets, also impairs glycolysis and glucose oxidation, decreases ATP concentration, and inhibits proinsulin biosynthesis. However, at a 10 micrometer concentration, menadione fails to affect the concentration of adenine nucleotides, the utilization of glucose, the production of lactate and pyruvate, the oxidation of [6-14C]glucose and the synthesis of proinsulin; whereas the metabolism of glucose through the pentose shunt is markedly increased. The sole inhibitory effect of menadione 10 micrometer upon metabolic parameters is to reduce the concentration of both NADH and NADPH, such an effect being noticed in islets exposed to glucose 11.1 mM but not in those incubated at a higher glucose level (27.8 mM). Since, in the presence of glucose 11.1 mM, menadione 10 micrometer also severely decreases glucose-stimulated45 calcium net uptake and subsequent insulin release, it is concluded that the availability of reduced pyridine nucleotides may play an essential role in the secretory sequence by coupling metabolic to cationic events. Thus, when insulinotropic nutrients are oxidized in the B-cell, the increased availability of reduced pyridine nucleotides could modify the affinity for cations of native ionophoretic systems, eventually leading to the accumulation of calcium up to a level sufficient to trigger insulin release."}
{"id": "PMID:27354", "title": "Characterization of deoxycytidylate methyltransferase in Xanthomonas oryzae infected with bacteriophage Xp12.", "content": "Three methods, chromatographic, spectrophotometric and tritium-release assay, were used and compared for the assay of deoxycytidylate methyltransferase. All three methods can be used for assay of this enzyme but the tritium-release assay appears to be the most simple and convenient. With the help of this assay the deoxycytidylate methyltransferase has been isolated and purified from sonically disrupted cells of Xp12-infected Xanthomonas oryzae. Using a procedure that involves fractionation with streptomycin sulfate and ammonium sulfate, filtration through Sephadex G-100 and chromatography on DEAE-cellulose, a 214-fold increase in specific activity was obtained. The enzyme displays a narrow pH optimum at 6.0 Among the buffers tested, 6-morpholinoethane sulfonate with the addition of Mg2 is the best. The enzyme can utilize dCMP as a substrate. The enzyme can also convert tetrahydrofolic acid into dihydrofolic acid. The Km value for dCMP is 31.3 micrometer and the Km value for tetrahydrofolic acid is 71.4 micrometer. There is no absolute requirement of ions for the activity of the enzyme; however, the presence of ions causes stimulating or inhibiting effects on enzyme activity that are dependent on the variety and concentration of ions used.", "contents": "Characterization of deoxycytidylate methyltransferase in Xanthomonas oryzae infected with bacteriophage Xp12. Three methods, chromatographic, spectrophotometric and tritium-release assay, were used and compared for the assay of deoxycytidylate methyltransferase. All three methods can be used for assay of this enzyme but the tritium-release assay appears to be the most simple and convenient. With the help of this assay the deoxycytidylate methyltransferase has been isolated and purified from sonically disrupted cells of Xp12-infected Xanthomonas oryzae. Using a procedure that involves fractionation with streptomycin sulfate and ammonium sulfate, filtration through Sephadex G-100 and chromatography on DEAE-cellulose, a 214-fold increase in specific activity was obtained. The enzyme displays a narrow pH optimum at 6.0 Among the buffers tested, 6-morpholinoethane sulfonate with the addition of Mg2 is the best. The enzyme can utilize dCMP as a substrate. The enzyme can also convert tetrahydrofolic acid into dihydrofolic acid. The Km value for dCMP is 31.3 micrometer and the Km value for tetrahydrofolic acid is 71.4 micrometer. There is no absolute requirement of ions for the activity of the enzyme; however, the presence of ions causes stimulating or inhibiting effects on enzyme activity that are dependent on the variety and concentration of ions used."}
{"id": "PMID:27358", "title": "Dependence upon pH of steady-state parameters for the beta-galactosidase-catalysed hydrolyses of beta-D-galactopyranosyl derivatives of different chemical types.", "content": "The effect of pH upon the beta-galactosidase-catalyzed hydrolyses of aryl galactosides is essentially similar for each of the three steps of their hydrolysis. It differs markedly from that on the hydrolysis of galactosyl pyridinium salts; these proceed through a 'non-bottleneck' pathway. While pH increase abolishes the rate of every step of the reaction for aryl galactosides, it favors the first step of hydrolysis of the galactosyl pyridinium salts, which supports the hypothesis that catalysis of these compounds originates largely in non-covalent interactions.", "contents": "Dependence upon pH of steady-state parameters for the beta-galactosidase-catalysed hydrolyses of beta-D-galactopyranosyl derivatives of different chemical types. The effect of pH upon the beta-galactosidase-catalyzed hydrolyses of aryl galactosides is essentially similar for each of the three steps of their hydrolysis. It differs markedly from that on the hydrolysis of galactosyl pyridinium salts; these proceed through a 'non-bottleneck' pathway. While pH increase abolishes the rate of every step of the reaction for aryl galactosides, it favors the first step of hydrolysis of the galactosyl pyridinium salts, which supports the hypothesis that catalysis of these compounds originates largely in non-covalent interactions."}
{"id": "PMID:27359", "title": "Effect of pH on the process of ternary-complex interconversion in the liver-alcohol-dehydrogenase reaction.", "content": "1. Kinetic relationships referring to multiple-turnover conditions have been derived for the slowest exponential transient appearing in two-substrate enzyme reactions proceeding by an ordered ternary-complex mechanism. The validity of these and previously derived theoretical relationships for this mechanism has been tested by application to the liver alcohol dehydrogenase reaction. 2. All essential features of the transient-state kinetics of alcohol oxidation by NAD+ in the liver alcohol dehydrogenase system can be qualitatively and quantitatively explained in view of the compulsory-order mechanism in the proposed scheme. There is no kinetic evidence for any half-of-the-sites reactivity of the enzyme. A consistent set of rate constants is reported for the enzymic oxidation of benzyl alcohol at pH 8.75. 3. Transient-state rate parameters for benzyl alcohol/benzaldehyde catalysis by liver alcohol dehydrogenase have been determined at different pH. The interpretation of such rate parameters is critically discussed with reference to their informative value for the purpose of determination of rate constants (k and k') for the process of ternary-complex interconversion in the proposed scheme. It is concluded that the apparent rate constant (k') for hydride transfer from benzyl alcohol to NAD+ is dependent on a proton dissociation step with a pKa of 6.4, whereas the rate constant (k) for hydride transfer from NADH to benzaldehyde exhibits no corresponding dependence on proton association. 4. The asymmetric pH dependence of the forward and reverse rate of ternary-complex interconversion during liver alcohol dehydrogenase catalysis appears to reflect an obligatory step of alcohol/alcoholate ion equilibration occurring at the ternary-complex level. It is suggested that the observed pKa 6.4 dependence of the transient rate of alcohol oxidation can be attributed to a coupled acid-base system involving minimally the enzyme-bound alcohol and the protein residues Ser-48 and His-51.", "contents": "Effect of pH on the process of ternary-complex interconversion in the liver-alcohol-dehydrogenase reaction. 1. Kinetic relationships referring to multiple-turnover conditions have been derived for the slowest exponential transient appearing in two-substrate enzyme reactions proceeding by an ordered ternary-complex mechanism. The validity of these and previously derived theoretical relationships for this mechanism has been tested by application to the liver alcohol dehydrogenase reaction. 2. All essential features of the transient-state kinetics of alcohol oxidation by NAD+ in the liver alcohol dehydrogenase system can be qualitatively and quantitatively explained in view of the compulsory-order mechanism in the proposed scheme. There is no kinetic evidence for any half-of-the-sites reactivity of the enzyme. A consistent set of rate constants is reported for the enzymic oxidation of benzyl alcohol at pH 8.75. 3. Transient-state rate parameters for benzyl alcohol/benzaldehyde catalysis by liver alcohol dehydrogenase have been determined at different pH. The interpretation of such rate parameters is critically discussed with reference to their informative value for the purpose of determination of rate constants (k and k') for the process of ternary-complex interconversion in the proposed scheme. It is concluded that the apparent rate constant (k') for hydride transfer from benzyl alcohol to NAD+ is dependent on a proton dissociation step with a pKa of 6.4, whereas the rate constant (k) for hydride transfer from NADH to benzaldehyde exhibits no corresponding dependence on proton association. 4. The asymmetric pH dependence of the forward and reverse rate of ternary-complex interconversion during liver alcohol dehydrogenase catalysis appears to reflect an obligatory step of alcohol/alcoholate ion equilibration occurring at the ternary-complex level. It is suggested that the observed pKa 6.4 dependence of the transient rate of alcohol oxidation can be attributed to a coupled acid-base system involving minimally the enzyme-bound alcohol and the protein residues Ser-48 and His-51."}
{"id": "PMID:27360", "title": "Isolation of a multiprotein complex containing cytochrome b and c1 from Neurospora crassa mitochondria by affinity chromatography on immobilized cytochrome c. Difference in the binding between ferricytochrome c and ferrocytochrome c to the multiprotein complex.", "content": "A multiprotein complex which contains in equimolar amounts two cytochromes b (Mr each about 27,000), one cytochrome c1 (Mr 31,000) and six subunits without known prosthetic groups (Mr 8000, 12,000, 14,000, 45,000, 45,000, and 50,000) has been isolated from the mitochondrial membranes of Neurospora crassa by affinity chromatography on immobilized cytochrome c. The chromatographic separation was based upon the specific binding of the complex to ferricytochrome c coupled to Sepharose and its specific release upon conversion of the coupled ferricytochrome c into ferrocytochrome c using ascorbate as a reductant. The chromatography was performed in the presence of the nonionic detergent Triton X-100 at low ionic strengths. A monodisperse preparation of the multiprotein complex was obtained which was used for binding studies with cytochrome c from Neurospora crassa, horse heart and Saccaromyces cerevisiae. At low ionic strength (20 mM Trisacetate) and slightly alkaline pH (pH 7 to 8), more than one molecule of ferricytochrome c were bound to the isolated multiprotein complex with dissociation constants below 1 x 10(-7) M. One of these bindings appeared different from the others, since its high affinity was preserved at an ionic strength at which the affinities of the other bindings decreased. Furthermore, the affinity of only this binding decreased upon reduction of cytochrome c. It is suggested that this binding is at or near the functionally active site(s) of the mulipprotein complex.", "contents": "Isolation of a multiprotein complex containing cytochrome b and c1 from Neurospora crassa mitochondria by affinity chromatography on immobilized cytochrome c. Difference in the binding between ferricytochrome c and ferrocytochrome c to the multiprotein complex. A multiprotein complex which contains in equimolar amounts two cytochromes b (Mr each about 27,000), one cytochrome c1 (Mr 31,000) and six subunits without known prosthetic groups (Mr 8000, 12,000, 14,000, 45,000, 45,000, and 50,000) has been isolated from the mitochondrial membranes of Neurospora crassa by affinity chromatography on immobilized cytochrome c. The chromatographic separation was based upon the specific binding of the complex to ferricytochrome c coupled to Sepharose and its specific release upon conversion of the coupled ferricytochrome c into ferrocytochrome c using ascorbate as a reductant. The chromatography was performed in the presence of the nonionic detergent Triton X-100 at low ionic strengths. A monodisperse preparation of the multiprotein complex was obtained which was used for binding studies with cytochrome c from Neurospora crassa, horse heart and Saccaromyces cerevisiae. At low ionic strength (20 mM Trisacetate) and slightly alkaline pH (pH 7 to 8), more than one molecule of ferricytochrome c were bound to the isolated multiprotein complex with dissociation constants below 1 x 10(-7) M. One of these bindings appeared different from the others, since its high affinity was preserved at an ionic strength at which the affinities of the other bindings decreased. Furthermore, the affinity of only this binding decreased upon reduction of cytochrome c. It is suggested that this binding is at or near the functionally active site(s) of the mulipprotein complex."}
{"id": "PMID:27361", "title": "Reduction of methemoglobin by cobaltocytochrome c catalyzed by mediators.", "content": "The reduction of methemoglobin by cobaltocytochrome c (Cocyt c) has been measured using nine mediators of different half-reduction potentials, Em, 7. The rate increases with the increase of Em, 7 for the mediator but dropped precipitously when it becomes more positive than the Em, 7 for the methemoglobin/hemoglobin couple. The reaction is most efficient with phenzaine methosulfate, therefore it was studied in detail. The reaction is first order in the concentrations of Cocyt c and phenazine methosulfate. The average second-order rate constant for Cocyt c + phenazine methosulfate (M) k1 leads to Cocyt c+ M-. is 2.9 x 10(4) M-1 s-1 at 25 degrees C, 0.1 M phosphate pH 7.0. There is a slight negative temperature dependence of k1 at low temperature; at higher temperatures the process has deltaH not equal to approximately 27 kJ mol-1 and deltaS not equal to approxmately - 75 J mol-1 K-1. The effect of anions reflects the dependence of Em, 7 for the methemoglobin/hemoglobin couple with various anions. There is no significant effect on k1 by the addition of inositol hexakisphosphate. The variation of k1 with pH is complicated. The experimental rate constants are compared with values calculated with the theory of nonadiabatic multiphonon process of electron tunneling.", "contents": "Reduction of methemoglobin by cobaltocytochrome c catalyzed by mediators. The reduction of methemoglobin by cobaltocytochrome c (Cocyt c) has been measured using nine mediators of different half-reduction potentials, Em, 7. The rate increases with the increase of Em, 7 for the mediator but dropped precipitously when it becomes more positive than the Em, 7 for the methemoglobin/hemoglobin couple. The reaction is most efficient with phenzaine methosulfate, therefore it was studied in detail. The reaction is first order in the concentrations of Cocyt c and phenazine methosulfate. The average second-order rate constant for Cocyt c + phenazine methosulfate (M) k1 leads to Cocyt c+ M-. is 2.9 x 10(4) M-1 s-1 at 25 degrees C, 0.1 M phosphate pH 7.0. There is a slight negative temperature dependence of k1 at low temperature; at higher temperatures the process has deltaH not equal to approximately 27 kJ mol-1 and deltaS not equal to approxmately - 75 J mol-1 K-1. The effect of anions reflects the dependence of Em, 7 for the methemoglobin/hemoglobin couple with various anions. There is no significant effect on k1 by the addition of inositol hexakisphosphate. The variation of k1 with pH is complicated. The experimental rate constants are compared with values calculated with the theory of nonadiabatic multiphonon process of electron tunneling."}
{"id": "PMID:27362", "title": "Nuclear-magnetic-resonance studies of 5'-ribonucleotide and 5'-deoxyribonucleotide conformations in solution using the lanthanide probe method.", "content": "The conformations of the metal-bound 5'-ribonucleotides and 5'-deoxyribonucleotides in aqueous solution at different pH values have been studied using the lanthanide probe method. The conformational analysis, based on mixing different conformations in fast exchange within the nuclear magnetic resonance time scale, agrees well with the results from coupling constants, nuclear Over-hauser effects and spin-lattice relaxation times, obtained for the metal-fixed systems. The equilibrium between the two basic conformational combinations for the 5'-nucleotides, anti-(N in equalibrium S)-gg-g'g' and syn-(N in equalibrium S)-gt-g'g' depends on the nature of the furanose ring, the base and also on the state of base protonation and phosphate ionization. The effect of base protonation is particularly strong for the guanine nucleotides.", "contents": "Nuclear-magnetic-resonance studies of 5'-ribonucleotide and 5'-deoxyribonucleotide conformations in solution using the lanthanide probe method. The conformations of the metal-bound 5'-ribonucleotides and 5'-deoxyribonucleotides in aqueous solution at different pH values have been studied using the lanthanide probe method. The conformational analysis, based on mixing different conformations in fast exchange within the nuclear magnetic resonance time scale, agrees well with the results from coupling constants, nuclear Over-hauser effects and spin-lattice relaxation times, obtained for the metal-fixed systems. The equilibrium between the two basic conformational combinations for the 5'-nucleotides, anti-(N in equalibrium S)-gg-g'g' and syn-(N in equalibrium S)-gt-g'g' depends on the nature of the furanose ring, the base and also on the state of base protonation and phosphate ionization. The effect of base protonation is particularly strong for the guanine nucleotides."}
{"id": "PMID:27363", "title": "Ecdysterone biosynthesis: a microsomal cytochrome-P-450-linked ecdysone 20-monooxygenase from tissues of the African migratory locust.", "content": "Ecdysone 20-monooxygenase, an enzyme which converts ecdysone to ecdysterone (the major moulting hormone of insects) has been characterized in cell-free preparations of tissues from African migratory locust. The product of the reaction has been identified as ecdysterone on the basis of several microchemical derivatization and chromatographic methods. Ecdysone 20-monooxygenase activity is located primarily in the microsomal fraction which also carries NADPH cytochrome c reductase and cytochrome P-450, as shown by sucrose density gradient centrifugation. Optimal conditions for the ecdysone 20-monooxygenase assay have been determined. The enzyme has a Km for ecdysone of 2.7 x 10(-7) M and is competitvely inhibited by ecdysterone (Ki = 7.5 x 10(-7) M). Ecdysone 20-monooxygenase is a typical cytochrome P-450 linked monooxygenase: the reaction requires O2 and is inhibited by CO, an effect partially reversed by white light. The enzyme is effectively inhibited by several specific monooxygenase inhibitors and by sulfhydryl reagents, but not by cyanide ions. Ecdysone elicits a type I difference spectrum when added to oxidized microsomes. NADPH acts as preferential electron donor. The transfer of reducing equivalents proceeds through NADPH cytochrome c (P-450) reductase: ecdysone 20-monooxygenase is inhibited by cytochrome c. Both NADPH cytochrome c reductase and ecdysone 20-monooxygenase are inhibited by NADP+ and show a similar Km for NADPH. The Malpighian tubules have the highest specific activity of ecdysone 20-monooxygenase, while fat body contain most of the cytochrome P-450 and NADPH cytochrome c reductase.", "contents": "Ecdysterone biosynthesis: a microsomal cytochrome-P-450-linked ecdysone 20-monooxygenase from tissues of the African migratory locust. Ecdysone 20-monooxygenase, an enzyme which converts ecdysone to ecdysterone (the major moulting hormone of insects) has been characterized in cell-free preparations of tissues from African migratory locust. The product of the reaction has been identified as ecdysterone on the basis of several microchemical derivatization and chromatographic methods. Ecdysone 20-monooxygenase activity is located primarily in the microsomal fraction which also carries NADPH cytochrome c reductase and cytochrome P-450, as shown by sucrose density gradient centrifugation. Optimal conditions for the ecdysone 20-monooxygenase assay have been determined. The enzyme has a Km for ecdysone of 2.7 x 10(-7) M and is competitvely inhibited by ecdysterone (Ki = 7.5 x 10(-7) M). Ecdysone 20-monooxygenase is a typical cytochrome P-450 linked monooxygenase: the reaction requires O2 and is inhibited by CO, an effect partially reversed by white light. The enzyme is effectively inhibited by several specific monooxygenase inhibitors and by sulfhydryl reagents, but not by cyanide ions. Ecdysone elicits a type I difference spectrum when added to oxidized microsomes. NADPH acts as preferential electron donor. The transfer of reducing equivalents proceeds through NADPH cytochrome c (P-450) reductase: ecdysone 20-monooxygenase is inhibited by cytochrome c. Both NADPH cytochrome c reductase and ecdysone 20-monooxygenase are inhibited by NADP+ and show a similar Km for NADPH. The Malpighian tubules have the highest specific activity of ecdysone 20-monooxygenase, while fat body contain most of the cytochrome P-450 and NADPH cytochrome c reductase."}
{"id": "PMID:27365", "title": "Ultramicro-electrophoresis of protein in sweat from patients with cystic fibrosis of the pancreas and controls.", "content": "46 sweat-samples from 32 children with cystic fibrosis of the pancreas (C.F.) and 35 samples from 23 control-children were collected with glass micro-capillaries. Protein was determined by ultramicro-electrophoresis. 1. Protein was detected in 48% of the samples (C.F. and controls). 2. At pH 2.3, C.F.-sweat showed at least one more band than control-sweat. 3. At pH 8.9, C.F.-sweat occasionally showed one more band than the control-group. 4. At pH 2.3, more protein was found at the electrophoresis start point using C.F.-sweat, whereas at pH 8.9 the opposite was found. 5. At pH 2.3, protein was found in fewer samples than at pH 8.9. The \"C.F.-factor\" is postulated to represent a basic polyelectrolyte which induces the following pathogenic mechanisms: a) Aggregation of proteins giving rise to a high viscosity of secretions, such as saliva. b) Binding to the cell-membrane of the glandular epithelium, thus inducing a disturbance of active NaCl-reabsorption (e.g. by reduction of luminal passive Na+-influx).", "contents": "Ultramicro-electrophoresis of protein in sweat from patients with cystic fibrosis of the pancreas and controls. 46 sweat-samples from 32 children with cystic fibrosis of the pancreas (C.F.) and 35 samples from 23 control-children were collected with glass micro-capillaries. Protein was determined by ultramicro-electrophoresis. 1. Protein was detected in 48% of the samples (C.F. and controls). 2. At pH 2.3, C.F.-sweat showed at least one more band than control-sweat. 3. At pH 8.9, C.F.-sweat occasionally showed one more band than the control-group. 4. At pH 2.3, more protein was found at the electrophoresis start point using C.F.-sweat, whereas at pH 8.9 the opposite was found. 5. At pH 2.3, protein was found in fewer samples than at pH 8.9. The \"C.F.-factor\" is postulated to represent a basic polyelectrolyte which induces the following pathogenic mechanisms: a) Aggregation of proteins giving rise to a high viscosity of secretions, such as saliva. b) Binding to the cell-membrane of the glandular epithelium, thus inducing a disturbance of active NaCl-reabsorption (e.g. by reduction of luminal passive Na+-influx)."}
{"id": "PMID:27366", "title": "Erythrocyte organic phosphates in the anemia of renal failure in childhood.", "content": "Erythrocyte 2,3-diphosphoglycerate (2,3-DPG ) and adenosinetriphosphate (ATP) levels were determined in 43 children with chronic renal failure on conservative treatment (CT), and 12 children on regular hemodialysis (HD) immediately before and after a HD session. The results were compared to non-anemic and anemic controls. In spite of anemia, erythrocyte 2,3-DPG in renal failure was similar to non-anemic controls at normal blood pH, but rose during dialysis as a result of alkalosis. In contrast, ATP levels were high already at a normal blood pH. 2,3-DPG correlated with packed cell volume (PCV) in children with renal failure but at lower concentrations compared to controls. Both organic phosphates in the erythrocytes showed a significant correlation with blood pH. The poor increase of 2,3-DPG, in combination with elevated ATP levels, suggests uremia-induced inhibition of 2,3-DPG synthesis.", "contents": "Erythrocyte organic phosphates in the anemia of renal failure in childhood. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG ) and adenosinetriphosphate (ATP) levels were determined in 43 children with chronic renal failure on conservative treatment (CT), and 12 children on regular hemodialysis (HD) immediately before and after a HD session. The results were compared to non-anemic and anemic controls. In spite of anemia, erythrocyte 2,3-DPG in renal failure was similar to non-anemic controls at normal blood pH, but rose during dialysis as a result of alkalosis. In contrast, ATP levels were high already at a normal blood pH. 2,3-DPG correlated with packed cell volume (PCV) in children with renal failure but at lower concentrations compared to controls. Both organic phosphates in the erythrocytes showed a significant correlation with blood pH. The poor increase of 2,3-DPG, in combination with elevated ATP levels, suggests uremia-induced inhibition of 2,3-DPG synthesis."}
{"id": "PMID:27367", "title": "Methylmalonic acidemia.", "content": "A patient presenting with severe metabolic acidosis accompanied by hyperglycinemia, hyperuricemia, hypoglycemia and hypertammonemia is described. Metabolic acidosis was found to be due to accumulated methylmalonic acid and did not respond to vitamin B12 administration. The patient showed favorable growth and development when kept on a low isoleucine, methionine, threonine and valine diet. In vitro studies using a lymphoid cell line derived from the patient showed a deficiency of methylmalonyl-CoA carbonyl-mutase.", "contents": "Methylmalonic acidemia. A patient presenting with severe metabolic acidosis accompanied by hyperglycinemia, hyperuricemia, hypoglycemia and hypertammonemia is described. Metabolic acidosis was found to be due to accumulated methylmalonic acid and did not respond to vitamin B12 administration. The patient showed favorable growth and development when kept on a low isoleucine, methionine, threonine and valine diet. In vitro studies using a lymphoid cell line derived from the patient showed a deficiency of methylmalonyl-CoA carbonyl-mutase."}
{"id": "PMID:27372", "title": "Controlled double-blind trial of camazepam, a new benzodiazepine derivative, versus chlordiazepoxide.", "content": "31 in-patients with anxiety entered at random in a double-blind clinical trial of chlordiazepoxide and camazepam, a benzodiazepine derivative. They were assessed by three different rating scales. Statistical evaluation of the results showed similar psychopharmacological activity of both drugs. It is concluded that camazepam is suitable for treatment of mild and severe anxiety states.", "contents": "Controlled double-blind trial of camazepam, a new benzodiazepine derivative, versus chlordiazepoxide. 31 in-patients with anxiety entered at random in a double-blind clinical trial of chlordiazepoxide and camazepam, a benzodiazepine derivative. They were assessed by three different rating scales. Statistical evaluation of the results showed similar psychopharmacological activity of both drugs. It is concluded that camazepam is suitable for treatment of mild and severe anxiety states."}
{"id": "PMID:27373", "title": "Phenprocoumon requirement, whole blood coagulation time, bleeding time and plasma gamma-GT in patients receiving mianserin.", "content": "A possible interaction between the tetracyclic antidepressant mianserin and a coumarin derivative has been investigated. Sixty-three subjects, 61 of whom required anticoagulant therapy for a variety of medical conditions, were treated for 5 consecutive weeks with phenprocoumon, in a dose adjusted to reduce the prothrombin time to 15%-25%. After an initial control period of one week, subjects were randomly treated under double-blind conditions with mianserin 3 X 10 mg daily or 3 X 20 mg daily, or with a matching placebo. The dose of mianserin was gradually increased to reach the maximum by the 6th day. Three subjects dropped out and 60 completed the trial. The dose of phenprocoumon and the prothrombin, bleeding, and coagulation times were not significantly affected by administration of mianserin. It can be concluded that there is no clinically important interaction between phenprocoumon and doses of mianserin effective in depression. Sedation was more frequent in patients taking mianserin than in those given placebo.", "contents": "Phenprocoumon requirement, whole blood coagulation time, bleeding time and plasma gamma-GT in patients receiving mianserin. A possible interaction between the tetracyclic antidepressant mianserin and a coumarin derivative has been investigated. Sixty-three subjects, 61 of whom required anticoagulant therapy for a variety of medical conditions, were treated for 5 consecutive weeks with phenprocoumon, in a dose adjusted to reduce the prothrombin time to 15%-25%. After an initial control period of one week, subjects were randomly treated under double-blind conditions with mianserin 3 X 10 mg daily or 3 X 20 mg daily, or with a matching placebo. The dose of mianserin was gradually increased to reach the maximum by the 6th day. Three subjects dropped out and 60 completed the trial. The dose of phenprocoumon and the prothrombin, bleeding, and coagulation times were not significantly affected by administration of mianserin. It can be concluded that there is no clinically important interaction between phenprocoumon and doses of mianserin effective in depression. Sedation was more frequent in patients taking mianserin than in those given placebo."}
{"id": "PMID:27369", "title": "Long-term blood pressure control with pindolol given once daily.", "content": "The antihypertensive effect of beta-adrenoceptor blocking drugs has been documented in a number of papers [10--13] and over the last 10 yr beta-receptor blockade has become a more and more frequent primary therapy for hypertension. During this time, a number of different beta-blockers with various degrees of selectivity, potency and intrinsic sympathomimetic effect have come into use. There have also been attempts to reduce the number of daily doses in beta-adrenoceptor blocking therapy while maintaining the antihypertensive effect [5]. Pindolol (Visk\u00e9n) is a beta-adrenoceptor blocking agent with intrinsic sympathomimetic effect and is characterized by high potency and long duration.", "contents": "Long-term blood pressure control with pindolol given once daily. The antihypertensive effect of beta-adrenoceptor blocking drugs has been documented in a number of papers [10--13] and over the last 10 yr beta-receptor blockade has become a more and more frequent primary therapy for hypertension. During this time, a number of different beta-blockers with various degrees of selectivity, potency and intrinsic sympathomimetic effect have come into use. There have also been attempts to reduce the number of daily doses in beta-adrenoceptor blocking therapy while maintaining the antihypertensive effect [5]. Pindolol (Visk\u00e9n) is a beta-adrenoceptor blocking agent with intrinsic sympathomimetic effect and is characterized by high potency and long duration."}
{"id": "PMID:27375", "title": "Participation of the sympathetic and the renin--angiotensin systems in blood pressure control during hypercapnia in the anaesthetized dog.", "content": "The effects of hypercapnia on plasma renin concentration and blood pressure were studied in anaesthetized dogs, untreated and after pretreatment with guanethidine, propranolol or prazosin. An increase in plasma renin concentration which accompanied hypercapnia in untreated dogs was completely suppressed by pretreatment with guanethidine or propranolol. Prazosin significantly reduced but did not abolish renin release during hypercapnia. The pressor response normally occurring during hypercapnia was abolished by propranolol and reversed by guanethidine and prazosin.", "contents": "Participation of the sympathetic and the renin--angiotensin systems in blood pressure control during hypercapnia in the anaesthetized dog. The effects of hypercapnia on plasma renin concentration and blood pressure were studied in anaesthetized dogs, untreated and after pretreatment with guanethidine, propranolol or prazosin. An increase in plasma renin concentration which accompanied hypercapnia in untreated dogs was completely suppressed by pretreatment with guanethidine or propranolol. Prazosin significantly reduced but did not abolish renin release during hypercapnia. The pressor response normally occurring during hypercapnia was abolished by propranolol and reversed by guanethidine and prazosin."}
{"id": "PMID:27376", "title": "Isoelectric focusing study of radiation damage to dry conalbumin.", "content": "The effect of gamma-rays on iron-free conalbumin was studied by isoelectric focusing technique. The results obtained can be interpreted on the basis of radiation-induced conformational changes of the macromolecules through a cleavage of disulphide bridges. Treatments with reagents acting on disulphide bridges lead to isoelectric focusing patterns that confirm this hypothesis.", "contents": "Isoelectric focusing study of radiation damage to dry conalbumin. The effect of gamma-rays on iron-free conalbumin was studied by isoelectric focusing technique. The results obtained can be interpreted on the basis of radiation-induced conformational changes of the macromolecules through a cleavage of disulphide bridges. Treatments with reagents acting on disulphide bridges lead to isoelectric focusing patterns that confirm this hypothesis."}
{"id": "PMID:27378", "title": "[Influence of isolanide and trasicor on the content of nicotinamide coenzymes in the myocardium of growing rats in hemic hypoxia].", "content": "Hemic hypoxia was produced in 7,30-day and 3--5-month old (adult) rats through introduction of sodium nitrite (100 mg/kg) with subsequent determination of the nicotinamide co-enzymes content in the myocardium. The effect of combined and separate application of the cardiac glycoside isolanide and beta-adrenoblocking agent trasicor under hypoxia at early stages of post-natal ontogenesis is shown.", "contents": "[Influence of isolanide and trasicor on the content of nicotinamide coenzymes in the myocardium of growing rats in hemic hypoxia]. Hemic hypoxia was produced in 7,30-day and 3--5-month old (adult) rats through introduction of sodium nitrite (100 mg/kg) with subsequent determination of the nicotinamide co-enzymes content in the myocardium. The effect of combined and separate application of the cardiac glycoside isolanide and beta-adrenoblocking agent trasicor under hypoxia at early stages of post-natal ontogenesis is shown."}
{"id": "PMID:27390", "title": "The cation composition of the seminal plasma and prostatic fluid and its correlation to semen quality.", "content": "The concentrations of calcium, magnesium, and zinc were measured by atomic absorption spectrometry. The concentrations of all three cations were found to be strongly correlated with one another and with acidity (pH). Analysis of the relative concentrations in prostatic fluid, split ejaculates, and whole seminal plasma confirmed an almost exclusively prostatic origin of these cations. Semen quality, as judged by motility, vitality, concentration, and morphology of spermatozoa, was inversely related to cation concentrations. Therefore, we recommend adoption of the measurement of seminal divalent cations as part of the routine andrologic examination.", "contents": "The cation composition of the seminal plasma and prostatic fluid and its correlation to semen quality. The concentrations of calcium, magnesium, and zinc were measured by atomic absorption spectrometry. The concentrations of all three cations were found to be strongly correlated with one another and with acidity (pH). Analysis of the relative concentrations in prostatic fluid, split ejaculates, and whole seminal plasma confirmed an almost exclusively prostatic origin of these cations. Semen quality, as judged by motility, vitality, concentration, and morphology of spermatozoa, was inversely related to cation concentrations. Therefore, we recommend adoption of the measurement of seminal divalent cations as part of the routine andrologic examination."}
{"id": "PMID:27391", "title": "Treatment of cryptorchidism with pernasal gonadotropin-releasing hormone therapy.", "content": "Twenty-five boys between 1 and 10 years of age with unilateral or bilateral cryptorchidism were treated with 200 microgram of gonadotropin-releasing hormone (GnRH) pernasally six times daily until descensus was completed, or for 10 weeks at most. Complete descent of the tests occurred in 16 patients, usually after 2 to 5 weeks of treatment. No adverse side effects have been observed. Radioimmunologic measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and prolactin, carried out before treatment, at the end of treatment, and 6 months after treatment, showed a transitory increase of the LH responsiveness to GnRH in only four of the patients and in the group as a whole a slight but significant decrease of FSH responsiveness. There were no signs of precocious puberty. GnRH antibodies were not found.", "contents": "Treatment of cryptorchidism with pernasal gonadotropin-releasing hormone therapy. Twenty-five boys between 1 and 10 years of age with unilateral or bilateral cryptorchidism were treated with 200 microgram of gonadotropin-releasing hormone (GnRH) pernasally six times daily until descensus was completed, or for 10 weeks at most. Complete descent of the tests occurred in 16 patients, usually after 2 to 5 weeks of treatment. No adverse side effects have been observed. Radioimmunologic measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and prolactin, carried out before treatment, at the end of treatment, and 6 months after treatment, showed a transitory increase of the LH responsiveness to GnRH in only four of the patients and in the group as a whole a slight but significant decrease of FSH responsiveness. There were no signs of precocious puberty. GnRH antibodies were not found."}
{"id": "PMID:27392", "title": "Treatment of cryptorchidism with a potent analog of gonadotropin-releasing hormone.", "content": "Pernasal therapy of cryptorchidism with D-Leu6-des-Gly10-gonadotropin-releasing hormone ethylamide (D-Leu6-des-Gly10-GnRH-EA), a potent, long-acting GnRH analog, was attempted. Eleven prepubertal cryptorchid boys received between 25 microgram once daily and 25 to 50 microgram twice daily for 5 to 12 weeks. Complete testicular descent was achieved in 4 of the 11 boys. GnRH tests (1.5 microgram/kg intravenously), conducted in six boys before treatment, after 4 weeks of treatment, and in 2 boys 3 months after treatment, did not reveal changes in gonadotropin secretion indicative of precocious puberty or of decreased hypophyseal sensitivity to GnRH. Antibodies to the GnRH analog or to GnRH could not be detected.", "contents": "Treatment of cryptorchidism with a potent analog of gonadotropin-releasing hormone. Pernasal therapy of cryptorchidism with D-Leu6-des-Gly10-gonadotropin-releasing hormone ethylamide (D-Leu6-des-Gly10-GnRH-EA), a potent, long-acting GnRH analog, was attempted. Eleven prepubertal cryptorchid boys received between 25 microgram once daily and 25 to 50 microgram twice daily for 5 to 12 weeks. Complete testicular descent was achieved in 4 of the 11 boys. GnRH tests (1.5 microgram/kg intravenously), conducted in six boys before treatment, after 4 weeks of treatment, and in 2 boys 3 months after treatment, did not reveal changes in gonadotropin secretion indicative of precocious puberty or of decreased hypophyseal sensitivity to GnRH. Antibodies to the GnRH analog or to GnRH could not be detected."}
{"id": "PMID:27393", "title": "Histochemical demonstration of glucose-6-phosphate dehydrogenase, D-sorbitol dehydrogenase, and alkaline phosphatase in human ampulla ductus deferentis.", "content": "A cytochemical study on the localization of the enzymes glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase, and alkaline phosphatase was carried out in human ampullary glands. Although the former two enzymes showed a marked reactivity, alkaline phosphatase was absent from epithelial cells. On the basis of these results it is concluded that, as in the human seminal vesicle, in the ampullary gland fructose is probably secreted via the oxidative mechanism proposed by Hers (Le Metabolisme du Fructose. Bruxelles, Arscia, 1957).", "contents": "Histochemical demonstration of glucose-6-phosphate dehydrogenase, D-sorbitol dehydrogenase, and alkaline phosphatase in human ampulla ductus deferentis. A cytochemical study on the localization of the enzymes glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase, and alkaline phosphatase was carried out in human ampullary glands. Although the former two enzymes showed a marked reactivity, alkaline phosphatase was absent from epithelial cells. On the basis of these results it is concluded that, as in the human seminal vesicle, in the ampullary gland fructose is probably secreted via the oxidative mechanism proposed by Hers (Le Metabolisme du Fructose. Bruxelles, Arscia, 1957)."}
{"id": "PMID:27396", "title": "Cytological analysis of bone marrow present in the bone nodules induced by human FL cells in mice.", "content": "Bone marrow cells recovered from bone nodules induced in mice by intramuscular transplantation of human FL cells were compared with the host femoral bone marrow. The precursors and mature forms of all types of blood cells were found in the induced bone marrow. The concentration of lymphocytes was significantly higher, and that of erythropoietic cells significantly lower in the induced bone marrow as compared with heterotopic femoral bone marrow.", "contents": "Cytological analysis of bone marrow present in the bone nodules induced by human FL cells in mice. Bone marrow cells recovered from bone nodules induced in mice by intramuscular transplantation of human FL cells were compared with the host femoral bone marrow. The precursors and mature forms of all types of blood cells were found in the induced bone marrow. The concentration of lymphocytes was significantly higher, and that of erythropoietic cells significantly lower in the induced bone marrow as compared with heterotopic femoral bone marrow."}
{"id": "PMID:27397", "title": "Evaluation of the local antihistaminic activity of dimetindene maleate by a quantitative method.", "content": "The topical application of a 0.1% dimetindene maleate gel on the forearms of 11 subjects reduces the areas of both erythema and wheal produced by the intradermal injection of 0.025 mg of histamine hydrochloride to a statistically greater degree than 1% d-chlorpheniramine maleate cream (p less than 0.005 and p less than 0.0005, respectively). The quantitative method employed in this study has proved to be an excellent means for the evaluation of the antihistaminic activity of topical preparations.", "contents": "Evaluation of the local antihistaminic activity of dimetindene maleate by a quantitative method. The topical application of a 0.1% dimetindene maleate gel on the forearms of 11 subjects reduces the areas of both erythema and wheal produced by the intradermal injection of 0.025 mg of histamine hydrochloride to a statistically greater degree than 1% d-chlorpheniramine maleate cream (p less than 0.005 and p less than 0.0005, respectively). The quantitative method employed in this study has proved to be an excellent means for the evaluation of the antihistaminic activity of topical preparations."}
{"id": "PMID:27398", "title": "[Sodium dichloracetate: its application to the therapeutics of experimental hyperiactatemia (author's transl)].", "content": "Different types of experimental hyperlactatemia and hyperpyruvicemia with or without lowering of blood pH were induced in anesthetized dogs. The initially studied experimental model was the hyperlactatemia and hyperpyruvicemia with lowering of blood pH induced by the intraduodenal administration of high doses of phenformin. Intravenous perfusion of sodium dichloroacetate (150 mg/kg infused during 20 minutes), which acts on the enzymatic complex of pyruvate dehydrogenase, reduced the hyperiactatemia and hyperpyruvicemia with or without acidosis provoked by phenformin injected intraduodenally (30 mg/kg), by intense muscular work, by hypoxia or by continous perfusion or adrenaline. Exogenous or endogenous insulin combined with sodium dichloracetate reduced the hyperlactatemia and hyperpyruvicemia as well as the changes in blood pH provoked by phenformin, more strongly than did sodium dichloroacetate alone. These findings have been confirmed in the conscious dog.", "contents": "[Sodium dichloracetate: its application to the therapeutics of experimental hyperiactatemia (author's transl)]. Different types of experimental hyperlactatemia and hyperpyruvicemia with or without lowering of blood pH were induced in anesthetized dogs. The initially studied experimental model was the hyperlactatemia and hyperpyruvicemia with lowering of blood pH induced by the intraduodenal administration of high doses of phenformin. Intravenous perfusion of sodium dichloroacetate (150 mg/kg infused during 20 minutes), which acts on the enzymatic complex of pyruvate dehydrogenase, reduced the hyperiactatemia and hyperpyruvicemia with or without acidosis provoked by phenformin injected intraduodenally (30 mg/kg), by intense muscular work, by hypoxia or by continous perfusion or adrenaline. Exogenous or endogenous insulin combined with sodium dichloracetate reduced the hyperlactatemia and hyperpyruvicemia as well as the changes in blood pH provoked by phenformin, more strongly than did sodium dichloroacetate alone. These findings have been confirmed in the conscious dog."}
{"id": "PMID:27399", "title": "Increased trypsin sensitivity of cell surface macromolecules after malignant transformation.", "content": "The effect of treatment with 0.04% (w/v) trypsin (EC 3.4.4.4) for 3 h on the electrophoretic mobility (EPM) of polyoma-virus malignantly transformed BHK21 cells (Py6) and their normal counterparts has been investigated. These particular conditions were chosen because an earlier study had shown that such treatment released material from the Py6 cells which was not obtained from the BHK21 cells. The negative EPM of the Py6 cells at pH 7.5 was greatly increased by this treatment; whereas the EPM of the BHK21 cells remained unchanged. Active enzyme was required to produce the change. No evidence was obtained for cytolysis, cytotoxicity or uptake of the enzyme by the treated Py6 cells. Measurement of the EPM of the Py6 cells at different pH levels before and after trypsin treatment suggested that the enzyme was removing cationic groupings from the cell surface.", "contents": "Increased trypsin sensitivity of cell surface macromolecules after malignant transformation. The effect of treatment with 0.04% (w/v) trypsin (EC 3.4.4.4) for 3 h on the electrophoretic mobility (EPM) of polyoma-virus malignantly transformed BHK21 cells (Py6) and their normal counterparts has been investigated. These particular conditions were chosen because an earlier study had shown that such treatment released material from the Py6 cells which was not obtained from the BHK21 cells. The negative EPM of the Py6 cells at pH 7.5 was greatly increased by this treatment; whereas the EPM of the BHK21 cells remained unchanged. Active enzyme was required to produce the change. No evidence was obtained for cytolysis, cytotoxicity or uptake of the enzyme by the treated Py6 cells. Measurement of the EPM of the Py6 cells at different pH levels before and after trypsin treatment suggested that the enzyme was removing cationic groupings from the cell surface."}
{"id": "PMID:27412", "title": "Relationship between site of peptic ulceration and gastric acid-peptic activity: new evaluation of gastric analysis in patients with acute gastric bleeding and chronic peptic ulcer.", "content": "In an attempt to elucidate the etiology of acute gastric bleeding and/or erosion and chronic peptic ulcer, a measurement of gastric juice and mucosal pepsin was carried out in surgically-treated patients. Patients with massive gastric mucosal bleeding in the fundic gland area showed high levels of fundic mucosal pepsin without acid-pepsin appearance in the gastric contents. In these patients, a significantly high value of the peptic activity ratio of gastric mucosa to gastric juice (MJPR, 36.4 +/- 6.7) was observed. It can be suggested that transient blockage of pepsin output from peptic cells with occur in the course of the acute mucosal bleeding, while acid-peptic digestion could be carried out within the fundic gland mucosa. On the other hand, a close correlation between relatively high acid-and-pepsin concentration of the gastric contents and a low level of MJPR (5.6 +/- 1.2) was observed in patients with chronic gastric ulcer. Patients who had a gastric ulcer within the pyloric gland mucosa had a highest acid-peptic activity among three groups with ulcers in fundic gland area, border zone and pyloric gland area. There is a rule that acid-peptic activity becomes low when the site of gastric ulcer moves from pylorus to fundus. A marked increase in acid-and-pepsin secretion into the gastric cavity was observed in patients suffering from chronic duodenal ulcer showing the lowest level of MJPR (3.40 +/- 0.50).", "contents": "Relationship between site of peptic ulceration and gastric acid-peptic activity: new evaluation of gastric analysis in patients with acute gastric bleeding and chronic peptic ulcer. In an attempt to elucidate the etiology of acute gastric bleeding and/or erosion and chronic peptic ulcer, a measurement of gastric juice and mucosal pepsin was carried out in surgically-treated patients. Patients with massive gastric mucosal bleeding in the fundic gland area showed high levels of fundic mucosal pepsin without acid-pepsin appearance in the gastric contents. In these patients, a significantly high value of the peptic activity ratio of gastric mucosa to gastric juice (MJPR, 36.4 +/- 6.7) was observed. It can be suggested that transient blockage of pepsin output from peptic cells with occur in the course of the acute mucosal bleeding, while acid-peptic digestion could be carried out within the fundic gland mucosa. On the other hand, a close correlation between relatively high acid-and-pepsin concentration of the gastric contents and a low level of MJPR (5.6 +/- 1.2) was observed in patients with chronic gastric ulcer. Patients who had a gastric ulcer within the pyloric gland mucosa had a highest acid-peptic activity among three groups with ulcers in fundic gland area, border zone and pyloric gland area. There is a rule that acid-peptic activity becomes low when the site of gastric ulcer moves from pylorus to fundus. A marked increase in acid-and-pepsin secretion into the gastric cavity was observed in patients suffering from chronic duodenal ulcer showing the lowest level of MJPR (3.40 +/- 0.50)."}
{"id": "PMID:27413", "title": "In vitro studies on mechanism for concentrating function of gallbladder.", "content": "The mechanism for concentrating function of gallbladder was studied in vitro, turning and attention to changes in the gallbladder bile composition, especially a marked increase of Na+ and a marked decrease of Cl- in the concentrating process of hepatic bile to gallbladder one. The following results were obtained by the present investigations: 1) bile acids present in bile regulate the rate of Na+ and Cl- transport: 2) the epithelial membrane of the gallbladder can be regarded as being a simple semi-permeable membrane.", "contents": "In vitro studies on mechanism for concentrating function of gallbladder. The mechanism for concentrating function of gallbladder was studied in vitro, turning and attention to changes in the gallbladder bile composition, especially a marked increase of Na+ and a marked decrease of Cl- in the concentrating process of hepatic bile to gallbladder one. The following results were obtained by the present investigations: 1) bile acids present in bile regulate the rate of Na+ and Cl- transport: 2) the epithelial membrane of the gallbladder can be regarded as being a simple semi-permeable membrane."}
{"id": "PMID:27414", "title": "Food sensitivity in reflux esophagitis.", "content": "We examined 66 patients with pain of possible esophageal origin for sensitivity to intraesophageal infusions of coffee, orange juice, spicy tomato drink, or HCl of varying concentrations as an addendum to their acid infusion (Bernstein) tests. Compared to Berstein-negative subjects, acid-sensitive patients were sensitive to infusion of coffee (P less than 0.01), orange juice (P less than 0.001), and tomato drink (P less than 0.001). Patients were largely insensitive to HCl solutions with a titratable acidity of 1 mEq per liter or less, less than the least acidic food solution tested. However, Berstein-positive patients were still highly sensitive to infusions of coffee, orange juice, and tomato drink adjusted to pH 7 (P less than 0.001). Patients were unable to differentiate symptoms caused by acid or food infusions, and solutions did not differ in the duration of infusion needed either to cause symptoms or to relieve them by saline. We conclude that the pain of esophagitis is nonspecific and can be precipitated by variety of seemingly unrelated substances.", "contents": "Food sensitivity in reflux esophagitis. We examined 66 patients with pain of possible esophageal origin for sensitivity to intraesophageal infusions of coffee, orange juice, spicy tomato drink, or HCl of varying concentrations as an addendum to their acid infusion (Bernstein) tests. Compared to Berstein-negative subjects, acid-sensitive patients were sensitive to infusion of coffee (P less than 0.01), orange juice (P less than 0.001), and tomato drink (P less than 0.001). Patients were largely insensitive to HCl solutions with a titratable acidity of 1 mEq per liter or less, less than the least acidic food solution tested. However, Berstein-positive patients were still highly sensitive to infusions of coffee, orange juice, and tomato drink adjusted to pH 7 (P less than 0.001). Patients were unable to differentiate symptoms caused by acid or food infusions, and solutions did not differ in the duration of infusion needed either to cause symptoms or to relieve them by saline. We conclude that the pain of esophagitis is nonspecific and can be precipitated by variety of seemingly unrelated substances."}
{"id": "PMID:27416", "title": "Intraluminal pH esophageal motility.", "content": "The aim of the present study was to investigate the effect of intraluminal pH on motor activity of the lower esophageal body. Liquid boluses of different pH values (7 to 2) were infused in the esophagus of 14 normal subjects during manometric recording of motor activity. Each test infusion elicited an esophageal motor response, either secondary peristalsis or simultaneous contractions. Secondary peristalsis was elicited by similar volumes of perfusates at pH 7, 6, 5, but significantly less volumes were needed with perfusates pH 4, 3, and 2. Simultaneous motor activity was not affected by intraesophageal pH value in the range investigated.", "contents": "Intraluminal pH esophageal motility. The aim of the present study was to investigate the effect of intraluminal pH on motor activity of the lower esophageal body. Liquid boluses of different pH values (7 to 2) were infused in the esophagus of 14 normal subjects during manometric recording of motor activity. Each test infusion elicited an esophageal motor response, either secondary peristalsis or simultaneous contractions. Secondary peristalsis was elicited by similar volumes of perfusates at pH 7, 6, 5, but significantly less volumes were needed with perfusates pH 4, 3, and 2. Simultaneous motor activity was not affected by intraesophageal pH value in the range investigated."}
{"id": "PMID:27418", "title": "[Riboflavin biosynthesis operon of Bacillus subtilis. XIII. Genetic and biochemical study of mutants with regard to intermediate stages of biosynthesis].", "content": "New riboflavin dependent mutants of Bacillus subtilis accumulating different pteridines were studied. The data obtained show that the formation of ribityl side chain proceeds in a few steps at least on a part of riboflavin precursors. The oxidation of connected ribosyl into ribulose with subsequent restoration of it into ribityl proceeds at first. The corresponding genes are located on terminal part of riboflavin operon, as show the results of two-factor transformational crosses with different donors and recipients.", "contents": "[Riboflavin biosynthesis operon of Bacillus subtilis. XIII. Genetic and biochemical study of mutants with regard to intermediate stages of biosynthesis]. New riboflavin dependent mutants of Bacillus subtilis accumulating different pteridines were studied. The data obtained show that the formation of ribityl side chain proceeds in a few steps at least on a part of riboflavin precursors. The oxidation of connected ribosyl into ribulose with subsequent restoration of it into ribityl proceeds at first. The corresponding genes are located on terminal part of riboflavin operon, as show the results of two-factor transformational crosses with different donors and recipients."}
{"id": "PMID:27425", "title": "Experimental and clinical investigations on stem cell take and colony formation.", "content": "First, lymphocyte transplantation into total body-irradiated rats is discussed. The effect on spleen colony formation caused by the transplantation of untreated lymphocytes, as well as of lymphocytes previously incubated with PHA, or with PHA plus L-asparaginase, or with lymphokines, was studied. Then the effect of the urinary colony-stimulating factor in vitro, and the in vitro feeder-layer activity of leucocytes on colony formation of human and mice bone marrow cells in haematological diseases is dealth with. The injection of rat lymphocytes previously incubated for 24 hours with PHA resulted in a higher number and a larger size of colonies in the spleen of the recipient rats. Lymphocytes preincubated with lymphokines gave rise to the formation of spleen colonies which were larger than those developing after the injection of untreated lymphocytes. When the lymphocytes were previously incubated with PHA plus L-asparaginase, PHA failed to stimulate colony formation in the spleen. The phenomenon is explained by assuming that PHA, as an aspecific stimulator of cell division, initiated the division of CFUs, thus the CFUs content of the preincubated samples increased, resulting in an increase in the number of colonies formed after the transplantation of lymphocytes pretreated with PHA. Another possible explanation is that CFUs division, or their spleen take is enhanced by the immunocompetent lymphocytes activated by PHA, either directly or via soluble mediators produced or released by immunocompetent lymphocytes such as lymphokines. The study of colony-forming cells and colony-stimulating activity in primary myelofibrosis (PM) showed an increase in the number of circulating CFUc in this condition, and an abnormal density of these cells reaching a peak below 1.062. The lowering of CSA in the first two peripheral blood gradient fractions agrees with the observation in the same fractions of a high percentage of CFUc at the expense of the CSC population. Thus, double cell population seems to exist in PM. One is greatly abnormal with a low specific density and high plating efficiency, whereas the other population is almost normal, showing a higher specific density and a lower plating efficiency.", "contents": "Experimental and clinical investigations on stem cell take and colony formation. First, lymphocyte transplantation into total body-irradiated rats is discussed. The effect on spleen colony formation caused by the transplantation of untreated lymphocytes, as well as of lymphocytes previously incubated with PHA, or with PHA plus L-asparaginase, or with lymphokines, was studied. Then the effect of the urinary colony-stimulating factor in vitro, and the in vitro feeder-layer activity of leucocytes on colony formation of human and mice bone marrow cells in haematological diseases is dealth with. The injection of rat lymphocytes previously incubated for 24 hours with PHA resulted in a higher number and a larger size of colonies in the spleen of the recipient rats. Lymphocytes preincubated with lymphokines gave rise to the formation of spleen colonies which were larger than those developing after the injection of untreated lymphocytes. When the lymphocytes were previously incubated with PHA plus L-asparaginase, PHA failed to stimulate colony formation in the spleen. The phenomenon is explained by assuming that PHA, as an aspecific stimulator of cell division, initiated the division of CFUs, thus the CFUs content of the preincubated samples increased, resulting in an increase in the number of colonies formed after the transplantation of lymphocytes pretreated with PHA. Another possible explanation is that CFUs division, or their spleen take is enhanced by the immunocompetent lymphocytes activated by PHA, either directly or via soluble mediators produced or released by immunocompetent lymphocytes such as lymphokines. The study of colony-forming cells and colony-stimulating activity in primary myelofibrosis (PM) showed an increase in the number of circulating CFUc in this condition, and an abnormal density of these cells reaching a peak below 1.062. The lowering of CSA in the first two peripheral blood gradient fractions agrees with the observation in the same fractions of a high percentage of CFUc at the expense of the CSC population. Thus, double cell population seems to exist in PM. One is greatly abnormal with a low specific density and high plating efficiency, whereas the other population is almost normal, showing a higher specific density and a lower plating efficiency."}
{"id": "PMID:27426", "title": "Effect of lanthanum ion on platelet electrophoretic mobility.", "content": "The effect of trivalent La ions on the elctrophoretic mobility of washed human platelets has been studied. The mobility of the human platelet in 0.145 M sodium chloride at pH 7.2 was -0.84 +/- 0.06 micron per sec per volt per cm with an isoelectric point approximately at pH 3.4 La3+ at a concentration corresponding to the physiological level of Ca2+ changed the sign of the electrophoretic mobility of the platelets at pH 5.5 and pH 4.0, but had only a faint or practically no effect at pH 3.0 and pH 2.0. It is assumed that La 3+ exerts its effect when bound to the phosphate groups on the surface.", "contents": "Effect of lanthanum ion on platelet electrophoretic mobility. The effect of trivalent La ions on the elctrophoretic mobility of washed human platelets has been studied. The mobility of the human platelet in 0.145 M sodium chloride at pH 7.2 was -0.84 +/- 0.06 micron per sec per volt per cm with an isoelectric point approximately at pH 3.4 La3+ at a concentration corresponding to the physiological level of Ca2+ changed the sign of the electrophoretic mobility of the platelets at pH 5.5 and pH 4.0, but had only a faint or practically no effect at pH 3.0 and pH 2.0. It is assumed that La 3+ exerts its effect when bound to the phosphate groups on the surface."}
{"id": "PMID:27427", "title": "Antihaemophilic factor (factor VIII) from human granulocytes.", "content": "Factor VIII has been isolated and purified from human granulocytes using chromatography on Sephadex G-200 AND DEAE-Sephadex A-50. The final preparation was purified 60-fold. Some properties of this partly purified factor VIII were compared with the human plasma AHF preparation. Optimum pH activity and the highest activity after incubation at different pH values was found in buffer at pH 7.0. The preparation was thermolabile and had a molecular weight of about 214,000. Absorption curves indicated that it is a protein exhibiting four fractions in polyacrylamide gel disk electrophoresis. AHF preparations from plasma and granulocytes were almost identical in the characteristics tested.", "contents": "Antihaemophilic factor (factor VIII) from human granulocytes. Factor VIII has been isolated and purified from human granulocytes using chromatography on Sephadex G-200 AND DEAE-Sephadex A-50. The final preparation was purified 60-fold. Some properties of this partly purified factor VIII were compared with the human plasma AHF preparation. Optimum pH activity and the highest activity after incubation at different pH values was found in buffer at pH 7.0. The preparation was thermolabile and had a molecular weight of about 214,000. Absorption curves indicated that it is a protein exhibiting four fractions in polyacrylamide gel disk electrophoresis. AHF preparations from plasma and granulocytes were almost identical in the characteristics tested."}
{"id": "PMID:27428", "title": "Some properties of an endo-1,4-beta-D-xylanase from the ligniperdous fungus Trametes hirsuta.", "content": "Some properties of purified endo-1,4-beta-D-xylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) from the ligniperdous fungus Trametes hirsuta were investigated. The enzyme was stable between pH 4.0 and 8.0 were optimum activity at pH 5.0--5.5. The temperature optimum was 50 degrees C and the enzyme was stable for up to 30 min at 45 degrees C; however, it was denatured at higher temperatures. The Km for 4-O-methylglucurono-D-xylan was 6.36.10(-3) equivalents of D-xylose per litre, the activation energy was 28 kJ mol-1. The molecular weight determined by means of gel chromatography was 22000--24000. The enzyme was activated by Ca2+ and inhibited by Ag+ and Hg2+. On the basis of the effect of 2-hydroxy-5-nitrobenzyl bromide. N-bromosuccinimide and N-acetylimidazole it may be assumed that trytophan and possibly tyrosine residues influence the enzyme catalysis.", "contents": "Some properties of an endo-1,4-beta-D-xylanase from the ligniperdous fungus Trametes hirsuta. Some properties of purified endo-1,4-beta-D-xylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) from the ligniperdous fungus Trametes hirsuta were investigated. The enzyme was stable between pH 4.0 and 8.0 were optimum activity at pH 5.0--5.5. The temperature optimum was 50 degrees C and the enzyme was stable for up to 30 min at 45 degrees C; however, it was denatured at higher temperatures. The Km for 4-O-methylglucurono-D-xylan was 6.36.10(-3) equivalents of D-xylose per litre, the activation energy was 28 kJ mol-1. The molecular weight determined by means of gel chromatography was 22000--24000. The enzyme was activated by Ca2+ and inhibited by Ag+ and Hg2+. On the basis of the effect of 2-hydroxy-5-nitrobenzyl bromide. N-bromosuccinimide and N-acetylimidazole it may be assumed that trytophan and possibly tyrosine residues influence the enzyme catalysis."}
{"id": "PMID:27430", "title": "[Psychopharmacologic drugs in the rehabilitation after myocardial infarct].", "content": "The specific use of psychotropic agents in myocardial infarction has become possible due to interdisciplinary cooperation. Especially the differentiated therapeutic application of benzodiazepine derivatives will take into better account the different psychopathologic states in the various phases. The medicamentous facilities are extended by using the central and peripheral effects of the beta-blockers. After a myocardial infarction there are various somatic and mental symptoms. This requires precise medical and psychological management with reference to a diagnostic and combined-therapeutic schedule of treatment. An intensive co-operation with all medical departments is a conditio sine qua non.", "contents": "[Psychopharmacologic drugs in the rehabilitation after myocardial infarct]. The specific use of psychotropic agents in myocardial infarction has become possible due to interdisciplinary cooperation. Especially the differentiated therapeutic application of benzodiazepine derivatives will take into better account the different psychopathologic states in the various phases. The medicamentous facilities are extended by using the central and peripheral effects of the beta-blockers. After a myocardial infarction there are various somatic and mental symptoms. This requires precise medical and psychological management with reference to a diagnostic and combined-therapeutic schedule of treatment. An intensive co-operation with all medical departments is a conditio sine qua non."}
{"id": "PMID:27437", "title": "[Insect bite allergy. Acute therapy and hyposensitization by means of insect venom].", "content": "Systemic reactions after an insect bite necessitate an allergologic investigation. In addition to taking the patient's history a skin test and an estimation of allergenspecific IgE should be performed. If insect bite allergy is confirmed immediate pharmacological treatment is necessary and hyposensitization therapy is recommended. Purified venom extracts are available.", "contents": "[Insect bite allergy. Acute therapy and hyposensitization by means of insect venom]. Systemic reactions after an insect bite necessitate an allergologic investigation. In addition to taking the patient's history a skin test and an estimation of allergenspecific IgE should be performed. If insect bite allergy is confirmed immediate pharmacological treatment is necessary and hyposensitization therapy is recommended. Purified venom extracts are available."}
{"id": "PMID:27438", "title": "[Acid-base equilibrium in the cerebrospinal fluid in diseases of the central nervous parenchyma].", "content": "A number of case studies reveal and dynamic changes of the acid-base balance in the blood and cerebrospinal fluid, such as the increasing decompensation of the metabolic lactate acidosis in the cerebrospinal fluid in lethal cases or the gradual regression in patients who were cured. Individual metabolic cerebrospinal parameters are correlated with the disturbance of consciousness. The cerebrospinal fluid parameters of patients with clouded consiciousness constitute prognostically critical values: lactate 3.6 mmol/l, pyruvate 0.19 mmol/l, pH 7.249 and bicarbonate 18.1 mmol/l. Affections of the central nervous parenchyma are better reflected in the cerebrospinal fluid than in the blood. The determination of the CSF/blood relationship of individual parameters shows a significant increase of the lactate quotient as well as a decrease of the pH quotient and of bicarbonate quotient. Respiratory parameters do not show any statistically significant changes. Statistically significant correlations show that, in the case of primary central nervous diseases, the increased hydrogen ion supply in the cerebrospinal fluid is quickly intercepted by the bicarbonate buffer and that, with a corresponding pH decrease, there is a rapid decompensation of the acid-base balance.", "contents": "[Acid-base equilibrium in the cerebrospinal fluid in diseases of the central nervous parenchyma]. A number of case studies reveal and dynamic changes of the acid-base balance in the blood and cerebrospinal fluid, such as the increasing decompensation of the metabolic lactate acidosis in the cerebrospinal fluid in lethal cases or the gradual regression in patients who were cured. Individual metabolic cerebrospinal parameters are correlated with the disturbance of consciousness. The cerebrospinal fluid parameters of patients with clouded consiciousness constitute prognostically critical values: lactate 3.6 mmol/l, pyruvate 0.19 mmol/l, pH 7.249 and bicarbonate 18.1 mmol/l. Affections of the central nervous parenchyma are better reflected in the cerebrospinal fluid than in the blood. The determination of the CSF/blood relationship of individual parameters shows a significant increase of the lactate quotient as well as a decrease of the pH quotient and of bicarbonate quotient. Respiratory parameters do not show any statistically significant changes. Statistically significant correlations show that, in the case of primary central nervous diseases, the increased hydrogen ion supply in the cerebrospinal fluid is quickly intercepted by the bicarbonate buffer and that, with a corresponding pH decrease, there is a rapid decompensation of the acid-base balance."}
{"id": "PMID:27440", "title": "Unilateral cryptorchidism with compensatory hypertrophy of descended testicle in prepubertal boys.", "content": "5 prepubertal boys with unilateral cryptorchidism and compensatory hypertrophy of the descended testicle, 22 prepubertal boys with unilateral cryptorchidism and without CTH, and 14 prepubertal normal boys were submitted to LH-RH and to HCG tests in order to study the hormonal behaviour in CTH phenomenon before puberty. High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation. On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones.", "contents": "Unilateral cryptorchidism with compensatory hypertrophy of descended testicle in prepubertal boys. 5 prepubertal boys with unilateral cryptorchidism and compensatory hypertrophy of the descended testicle, 22 prepubertal boys with unilateral cryptorchidism and without CTH, and 14 prepubertal normal boys were submitted to LH-RH and to HCG tests in order to study the hormonal behaviour in CTH phenomenon before puberty. High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation. On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones."}
{"id": "PMID:27442", "title": "Carcinoma in situ of the testis: frequency and relationship to invasive germ cell tumours in infertile men.", "content": "A light microscopical study on a total of 812 consecutive testicular biopsies from 555 infertile men revealed intratubular changes in germ cells compatible with a carcinoma in situ pattern in six oligospermic patients (I.I%); the changes were found in both testes in two of these men. Four of the six patients developed an invasive germ cell tumour within follow-up period of 1.3 to 4.5 years. The results confirm the malignant nature of these intratubular atypical germ cells. It is concluded that testicular biopsy may be useful for early detection and cure of germ cell carcinoma in patients at risk, i.e. patients with cryptorchidism, infertile men or patients with previous cancer of one testis.", "contents": "Carcinoma in situ of the testis: frequency and relationship to invasive germ cell tumours in infertile men. A light microscopical study on a total of 812 consecutive testicular biopsies from 555 infertile men revealed intratubular changes in germ cells compatible with a carcinoma in situ pattern in six oligospermic patients (I.I%); the changes were found in both testes in two of these men. Four of the six patients developed an invasive germ cell tumour within follow-up period of 1.3 to 4.5 years. The results confirm the malignant nature of these intratubular atypical germ cells. It is concluded that testicular biopsy may be useful for early detection and cure of germ cell carcinoma in patients at risk, i.e. patients with cryptorchidism, infertile men or patients with previous cancer of one testis."}
{"id": "PMID:27443", "title": "G6PD Vientiane: a new glucose-6-phosphate dehydrogenase variant with increased stability.", "content": "A new G6PD variant, called G6PD Vientiane, has been discovered in a patient from Laos. The characteristics of this variant are: mild enzyme deficiency (about 50% of the normal activity) in the granulocytes and the red cells, with normal G6PD-related antigen concentration; increased stability; normal Km glucose 6-phosphate and NADP+; increased inhibition constant by NADPH; decreased inhibition by ATP; slightly increased utilization of the substrate analogue; abnormal pH curve, with maximum activity at pH 9.5; slightly reduced starch gel electrophoretic migration. The implications of the molecular stability of a deficient mutant variant are discussed.", "contents": "G6PD Vientiane: a new glucose-6-phosphate dehydrogenase variant with increased stability. A new G6PD variant, called G6PD Vientiane, has been discovered in a patient from Laos. The characteristics of this variant are: mild enzyme deficiency (about 50% of the normal activity) in the granulocytes and the red cells, with normal G6PD-related antigen concentration; increased stability; normal Km glucose 6-phosphate and NADP+; increased inhibition constant by NADPH; decreased inhibition by ATP; slightly increased utilization of the substrate analogue; abnormal pH curve, with maximum activity at pH 9.5; slightly reduced starch gel electrophoretic migration. The implications of the molecular stability of a deficient mutant variant are discussed."}
{"id": "PMID:27444", "title": "Growth and embryo formation in wild-carrot suspension cultures with ammonium ion as a sole nitrogen source.", "content": "Wild-carrot (Daucus carota L.) suspension cultures grew and produced embryos on ammonium ion as a sole source of nitrogen in the absence of any exogenous Kreb's cycle acid when the pH of the medium was controlled by continuous titration with with KOH or KHCO3.", "contents": "Growth and embryo formation in wild-carrot suspension cultures with ammonium ion as a sole nitrogen source. Wild-carrot (Daucus carota L.) suspension cultures grew and produced embryos on ammonium ion as a sole source of nitrogen in the absence of any exogenous Kreb's cycle acid when the pH of the medium was controlled by continuous titration with with KOH or KHCO3."}
{"id": "PMID:27445", "title": "Initiation and characterization of a diploid cell line from larval tissues of Aedes dorsalis (Meigen).", "content": "Mosquito cell cultures were initiated from the minced tissues of newly hatched Aedes dorsalis (Meigen) larvae. Continuous cell division occurred only after an adaptive period of approximately 6 months. Optimal growth of the cells required a relatively low pH of 6.5. Karyological studies showed that the cells have remained diploid (2n = 6) for 60 serial passages and that the cultures are free of contaminating cells. The cultures also were shown to be free of bacteria (including Mycoplasma), fungi and virions. Subpopulations (strains) of the original parental cultures have been selected and characterized on the basis of morphology, karyology, growth rate and monolayer formation.", "contents": "Initiation and characterization of a diploid cell line from larval tissues of Aedes dorsalis (Meigen). Mosquito cell cultures were initiated from the minced tissues of newly hatched Aedes dorsalis (Meigen) larvae. Continuous cell division occurred only after an adaptive period of approximately 6 months. Optimal growth of the cells required a relatively low pH of 6.5. Karyological studies showed that the cells have remained diploid (2n = 6) for 60 serial passages and that the cultures are free of contaminating cells. The cultures also were shown to be free of bacteria (including Mycoplasma), fungi and virions. Subpopulations (strains) of the original parental cultures have been selected and characterized on the basis of morphology, karyology, growth rate and monolayer formation."}
{"id": "PMID:27446", "title": "gamma-Glutamyltransferase in human diploid fibroblasts and other mammalian cells.", "content": "gamma-Glutamyltransferase was determined in WI-38 human diploid fibroblasts and compared to enzyme levels determined in several other mammalian cell lines including: fibroblast-like cells from human skin, tibia and foreskin; epithelial-like cells from human, bovine and monkey kidney; and transformed cells (Chinese hamster ovary, HeLa S3 and SV-40 transformed WI-38). Transformed cells had the lowest activity found followed in increasing order by fibroblasts, human and bovine epithelial cells and monkey kidney epithelial cells. The enzyme isolated from the plasma membrane of WI-38 cells, like the enzyme from kidney and brain, was found to be irreversibly inhibited by iodoacetamide, reversibly by serine-borate, and had a strong specificity for certain amino acids. The possibility exists that gamma-glutamyltransferase could be involved in transport of amino acids into cells in culture; and glutamine, used in media, is an excellent substrate for the enzyme.", "contents": "gamma-Glutamyltransferase in human diploid fibroblasts and other mammalian cells. gamma-Glutamyltransferase was determined in WI-38 human diploid fibroblasts and compared to enzyme levels determined in several other mammalian cell lines including: fibroblast-like cells from human skin, tibia and foreskin; epithelial-like cells from human, bovine and monkey kidney; and transformed cells (Chinese hamster ovary, HeLa S3 and SV-40 transformed WI-38). Transformed cells had the lowest activity found followed in increasing order by fibroblasts, human and bovine epithelial cells and monkey kidney epithelial cells. The enzyme isolated from the plasma membrane of WI-38 cells, like the enzyme from kidney and brain, was found to be irreversibly inhibited by iodoacetamide, reversibly by serine-borate, and had a strong specificity for certain amino acids. The possibility exists that gamma-glutamyltransferase could be involved in transport of amino acids into cells in culture; and glutamine, used in media, is an excellent substrate for the enzyme."}
{"id": "PMID:27454", "title": "Filamentous capsulated streptococci from the human respiratory tract: chemical and immunochemical characterization of a glycoprotein capsular antigen of provisional binary capsular type 87.", "content": "A filamentous alpha-hemolytic streptococcus of provisional capsular type 87 isolated from the human respiratory tract has been shown to be binary capsulated. One of the capsular antigens appears to be a glycoprotein; the other appears to be a polysaccharide. Transformation reactions with deoxyribonucleic acid from streptococcus type 87 and a number of noncapsulated pneumococci yielded transformed pneumococci with either a glycoprotein capsule or a polysaccharide capsule, but not with both. Capsular precipitin (quellung) reactions were observed when streptococcus type 87 was treated with homologous antiserum or with antisera to either of the two distinct capsular transformants. Each of the transformed pneumococci gave a quellung reaction with its homologous antiserum or with antiserum to streptococcus type 87, but neither reacted with antiserum to the heterologous transformant. Chemical analysis showed the glycoprotein antigen of streptococcus type 87 to contain, in addition to amino acids, glucose, galactose, glucosamine, and phosphate. The amino acid composition of the glycoprotein capsular antigens from streptococcus type 87 and of those from transformed pneumococci were similar, showing only minor differences. The glycoprotein capsular antigen from streptococcus type 87 gave two closely associated precipitin bands with homologous antiserum or antisera to transformed pneumococci with the glycoprotein capsule. That the two precipitin bands represent two unrelated proteins is precluded largely on the basis of the unlikely probability of 100% cotransformation of the genes coding for both proteins in the pneumococcal transformants that were isolated. Chemical analyses of the various fractions of the glycoprotein indicate that the two precipitin bands may represent a glycoprotein and its corresponding apoprotein.", "contents": "Filamentous capsulated streptococci from the human respiratory tract: chemical and immunochemical characterization of a glycoprotein capsular antigen of provisional binary capsular type 87. A filamentous alpha-hemolytic streptococcus of provisional capsular type 87 isolated from the human respiratory tract has been shown to be binary capsulated. One of the capsular antigens appears to be a glycoprotein; the other appears to be a polysaccharide. Transformation reactions with deoxyribonucleic acid from streptococcus type 87 and a number of noncapsulated pneumococci yielded transformed pneumococci with either a glycoprotein capsule or a polysaccharide capsule, but not with both. Capsular precipitin (quellung) reactions were observed when streptococcus type 87 was treated with homologous antiserum or with antisera to either of the two distinct capsular transformants. Each of the transformed pneumococci gave a quellung reaction with its homologous antiserum or with antiserum to streptococcus type 87, but neither reacted with antiserum to the heterologous transformant. Chemical analysis showed the glycoprotein antigen of streptococcus type 87 to contain, in addition to amino acids, glucose, galactose, glucosamine, and phosphate. The amino acid composition of the glycoprotein capsular antigens from streptococcus type 87 and of those from transformed pneumococci were similar, showing only minor differences. The glycoprotein capsular antigen from streptococcus type 87 gave two closely associated precipitin bands with homologous antiserum or antisera to transformed pneumococci with the glycoprotein capsule. That the two precipitin bands represent two unrelated proteins is precluded largely on the basis of the unlikely probability of 100% cotransformation of the genes coding for both proteins in the pneumococcal transformants that were isolated. Chemical analyses of the various fractions of the glycoprotein indicate that the two precipitin bands may represent a glycoprotein and its corresponding apoprotein."}
{"id": "PMID:27455", "title": "Filamentous capsulated streptococci from the human respiratory tract: chemical and immunochemical characterization of the polysaccharide capsular antigen of provisional binary capsular type 87.", "content": "The polysaccharide capsular antigen of the filamentous binary capsulated streptococcus of provisional type 87 and the polysaccharide capsular antigens of two pneumoccal strains transformed with deoxyribonucleic acid of streptococus type 87 have been purified and analyzed with regard to their component monosaccharides. The purified polysaccharides from the three strains were immunochemically identical. Each was found to contain rhamnose, glucose, galactose, galactosamine, and phosphate. Rhamnose was the immunodominant sugar.", "contents": "Filamentous capsulated streptococci from the human respiratory tract: chemical and immunochemical characterization of the polysaccharide capsular antigen of provisional binary capsular type 87. The polysaccharide capsular antigen of the filamentous binary capsulated streptococcus of provisional type 87 and the polysaccharide capsular antigens of two pneumoccal strains transformed with deoxyribonucleic acid of streptococus type 87 have been purified and analyzed with regard to their component monosaccharides. The purified polysaccharides from the three strains were immunochemically identical. Each was found to contain rhamnose, glucose, galactose, galactosamine, and phosphate. Rhamnose was the immunodominant sugar."}
{"id": "PMID:27456", "title": "Heat-stable enterotoxin from Escherichia coli: factors involved in growth and toxin production.", "content": "Six enterotoxigenic strains of Escherichia coli produced variable levels of heat-stable enterotoxin (ST) when grown under pH control at 8.5 in a simple synthetic medium containing neither amino acids nor vitamins. Bacterial growth and ST production were at levels as high as or higher than those observed in complex media. ST elaboration was detectable in the early logarithmic phase of growth and appeared to be related to disappearance of glucose in the growth medium. The results of this study did not suggest pH-dependent release of ST. Imposition of pH control in complex media resulted in increased growth rates, earlier detectable ST synthesis, and elevated levels of ST. In synthetic medium, attainment of the stationary growth phase was followed by a significant decrease in culture density and a concomitant increase in ST. Cellular autolysis experiments revealed that as much as 20% of the total ST activity was present in a cell-associated form.", "contents": "Heat-stable enterotoxin from Escherichia coli: factors involved in growth and toxin production. Six enterotoxigenic strains of Escherichia coli produced variable levels of heat-stable enterotoxin (ST) when grown under pH control at 8.5 in a simple synthetic medium containing neither amino acids nor vitamins. Bacterial growth and ST production were at levels as high as or higher than those observed in complex media. ST elaboration was detectable in the early logarithmic phase of growth and appeared to be related to disappearance of glucose in the growth medium. The results of this study did not suggest pH-dependent release of ST. Imposition of pH control in complex media resulted in increased growth rates, earlier detectable ST synthesis, and elevated levels of ST. In synthetic medium, attainment of the stationary growth phase was followed by a significant decrease in culture density and a concomitant increase in ST. Cellular autolysis experiments revealed that as much as 20% of the total ST activity was present in a cell-associated form."}
{"id": "PMID:27457", "title": "Allosteric transformation of reduced nicotinamide adenine dinucleotide (phosphate) oxidase induced by phagocytosis in human polymorphonuclear leukocytes.", "content": "We used sensitive isotopic and fluorometric assay procedures to investigate reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]oxidation in a particulate fraction derived from normal and chronic granulomatous disease leukocytes. Granules isolated from normal resting cells showed allosteric kinetics with regard to oxidation of either NADH or NADPH, so that no enzyme activity was observed at physiological concentrations of substrate. If the granules were isolated from cells that had previously phagocytized zymosan, normal hyperbolic kinetics were obtained, so that activity could now be observed at low levels of substrate. The activity towards NADPH was always substantially greater than that towards NADH at any given concentration of substrate. This alteration in kinetics with phagocytosis was not observed with the other granule enzymes, acid phosphatase or beta-glucuronidase, and thus appeared to be specific for the reduced pyridine nucleotide oxidase(s). In contrast, granules isolated from cells of patients with chronic granulomatous disease showed allosteric kinetics regardless of whether they were obtained from resting or phagocytizing cells, so that NADPH oxidation was not measurable at physiological concentrations of substrate. This defect in the oxidation of NADPH by granules isolated from phagocytizing chronic granulomatous disease cells was observed over the pH range of 4.0 to 7.0. These data suggest that initiation of the respiratory burst by pahgocytosis normally requires an allosteric transformation in a reduced pyridine nucleotide oxidase, which in turn allows expression of enzymatic activity at physiological concentrations of substrate. The defect in chronic granulomatous disease appears to lie in an inability to achieve this transformation, and the enzyme remains in the inactive, allosteric form.", "contents": "Allosteric transformation of reduced nicotinamide adenine dinucleotide (phosphate) oxidase induced by phagocytosis in human polymorphonuclear leukocytes. We used sensitive isotopic and fluorometric assay procedures to investigate reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]oxidation in a particulate fraction derived from normal and chronic granulomatous disease leukocytes. Granules isolated from normal resting cells showed allosteric kinetics with regard to oxidation of either NADH or NADPH, so that no enzyme activity was observed at physiological concentrations of substrate. If the granules were isolated from cells that had previously phagocytized zymosan, normal hyperbolic kinetics were obtained, so that activity could now be observed at low levels of substrate. The activity towards NADPH was always substantially greater than that towards NADH at any given concentration of substrate. This alteration in kinetics with phagocytosis was not observed with the other granule enzymes, acid phosphatase or beta-glucuronidase, and thus appeared to be specific for the reduced pyridine nucleotide oxidase(s). In contrast, granules isolated from cells of patients with chronic granulomatous disease showed allosteric kinetics regardless of whether they were obtained from resting or phagocytizing cells, so that NADPH oxidation was not measurable at physiological concentrations of substrate. This defect in the oxidation of NADPH by granules isolated from phagocytizing chronic granulomatous disease cells was observed over the pH range of 4.0 to 7.0. These data suggest that initiation of the respiratory burst by pahgocytosis normally requires an allosteric transformation in a reduced pyridine nucleotide oxidase, which in turn allows expression of enzymatic activity at physiological concentrations of substrate. The defect in chronic granulomatous disease appears to lie in an inability to achieve this transformation, and the enzyme remains in the inactive, allosteric form."}
{"id": "PMID:27458", "title": "Cell envelope of Neisseria gonorrhoeae: phospholipase activity and its relationship to autolysis.", "content": "The relationship between conditions which permit or inhibit cell lysis and those which promote phospholipid hydrolysis in Neisseria gonorrhoeae was investigated. Suspension of exponential-phase gonococci in buffer in the absence of divalent cations resulted in autolysis but not in phosphlipid hydrolysis. The addition of Ca2+ or Mg2+ to the buffer inhibited autolysis and markedly stimulated the hydrolysis of phosphatidylethanolamine. Incubation of cells in buffer at pH 6 inhibited both autolysis and phospholipid hydrolysis.", "contents": "Cell envelope of Neisseria gonorrhoeae: phospholipase activity and its relationship to autolysis. The relationship between conditions which permit or inhibit cell lysis and those which promote phospholipid hydrolysis in Neisseria gonorrhoeae was investigated. Suspension of exponential-phase gonococci in buffer in the absence of divalent cations resulted in autolysis but not in phosphlipid hydrolysis. The addition of Ca2+ or Mg2+ to the buffer inhibited autolysis and markedly stimulated the hydrolysis of phosphatidylethanolamine. Incubation of cells in buffer at pH 6 inhibited both autolysis and phospholipid hydrolysis."}
{"id": "PMID:27459", "title": "Immunochemical studies on a Mycoplasma pneumoniae polysaccharide fraction: cross-reactions with type 23 and 32 antipneumococcal rabbit sera.", "content": "Lipid-free polysaccharide fraction 2 extracted from Mycoplasma pneumoniae strain FH by Prescott et al. (J. Bacteriol. 91:2117-2115, 1966) was examined for its ability to cross-precipitate antibody from type-specific rabbit antipneumococcal sera types 1 to 34 inclusive. Cross-precipitation in type-specific pneumococcal anti-type 23 and anti-type 32 sera was examined in detail and could be attributed to a rhamnose-galactose-rich component of crude M. pneumoniae polysaccharide fraction 2 recovered from immunoprecipitates formed with anti-type 23 serum. Immunochemically isolated mycoplasma polysaccharide was found to contain glucose, galactose, rhamnose, and mannose in 1:14:5:4 molar proportions. Comparison of the ability of 6-O-alpha-L-rhamnosyl-D-glucose and free L-rhamnose to inhibit precepitation by homologous pneumococcal and heterologous mycoplasma polysaccharide antigens indicates a combining site specificity for anti-type 23 and anti-type 32 antibodies directed largely against the alpha-linked L-rhamnosyl determinants and the occurrence of alpha-L-rhamnosyl units in type 32 and M. pneumoniae polysaccharides. Hapten inhibition of the cross-precipitation of pneumococcal type 23 capsular polysaccharide in anti-type 32 serum helps to establish that cross-reactivity can be attributed to interaction of recurrent, alpha-L-rhamnosyl units of type 23 with anit-alpha-L-rhamnoside combining sites of anti-type 32 antibodies.", "contents": "Immunochemical studies on a Mycoplasma pneumoniae polysaccharide fraction: cross-reactions with type 23 and 32 antipneumococcal rabbit sera. Lipid-free polysaccharide fraction 2 extracted from Mycoplasma pneumoniae strain FH by Prescott et al. (J. Bacteriol. 91:2117-2115, 1966) was examined for its ability to cross-precipitate antibody from type-specific rabbit antipneumococcal sera types 1 to 34 inclusive. Cross-precipitation in type-specific pneumococcal anti-type 23 and anti-type 32 sera was examined in detail and could be attributed to a rhamnose-galactose-rich component of crude M. pneumoniae polysaccharide fraction 2 recovered from immunoprecipitates formed with anti-type 23 serum. Immunochemically isolated mycoplasma polysaccharide was found to contain glucose, galactose, rhamnose, and mannose in 1:14:5:4 molar proportions. Comparison of the ability of 6-O-alpha-L-rhamnosyl-D-glucose and free L-rhamnose to inhibit precepitation by homologous pneumococcal and heterologous mycoplasma polysaccharide antigens indicates a combining site specificity for anti-type 23 and anti-type 32 antibodies directed largely against the alpha-linked L-rhamnosyl determinants and the occurrence of alpha-L-rhamnosyl units in type 32 and M. pneumoniae polysaccharides. Hapten inhibition of the cross-precipitation of pneumococcal type 23 capsular polysaccharide in anti-type 32 serum helps to establish that cross-reactivity can be attributed to interaction of recurrent, alpha-L-rhamnosyl units of type 23 with anit-alpha-L-rhamnoside combining sites of anti-type 32 antibodies."}
{"id": "PMID:27460", "title": "Activation of alveolar macrophages exposed to lavage-procured immunoglobulin G obtained from normal rabbit lungs.", "content": "Pulmonary washings from rabbits were freed of cells and added to the monolayers of homologous alveolar macrophages (AM). At 1 h after incubation with the pulmonary washings, many more cells adhered to glass, spread out, and showed enhanced Nitro Blue Tetrazolium reduction. The maximal effect of the pulmonary washings on AM activation was obtained 12 h after incubation. The AM activated by the pulmonary washings showed a higher capacity to inhibit the growth of intracellular BCG, and that capacity was correlated with the intensity of Nitro Blue Tetrazolium reduction by the AM. Gel filtration of the pulmonary washings through Sepharose 4B yielded five fractions. The factor that activated the AM functions was in fraction 4. When the immunoglobulin G in the fraction was removed by an immunoadsorbent column, AM activity was abolished. The effect of the immunoglobulin G was dose dependent, and minimal responses to 10(6) cells per ml were obtained at a protein concentration of 20 mug/ml. Lymphokines had no effect on AM activation with respect to the morphological alterations and Nitro Blue Tetrazolium reduction during the 24-h observation time. In summary, AM from normal rabbits were soon activated markedly by lavage-procured immunoglobulin G, but not by lymphokines.", "contents": "Activation of alveolar macrophages exposed to lavage-procured immunoglobulin G obtained from normal rabbit lungs. Pulmonary washings from rabbits were freed of cells and added to the monolayers of homologous alveolar macrophages (AM). At 1 h after incubation with the pulmonary washings, many more cells adhered to glass, spread out, and showed enhanced Nitro Blue Tetrazolium reduction. The maximal effect of the pulmonary washings on AM activation was obtained 12 h after incubation. The AM activated by the pulmonary washings showed a higher capacity to inhibit the growth of intracellular BCG, and that capacity was correlated with the intensity of Nitro Blue Tetrazolium reduction by the AM. Gel filtration of the pulmonary washings through Sepharose 4B yielded five fractions. The factor that activated the AM functions was in fraction 4. When the immunoglobulin G in the fraction was removed by an immunoadsorbent column, AM activity was abolished. The effect of the immunoglobulin G was dose dependent, and minimal responses to 10(6) cells per ml were obtained at a protein concentration of 20 mug/ml. Lymphokines had no effect on AM activation with respect to the morphological alterations and Nitro Blue Tetrazolium reduction during the 24-h observation time. In summary, AM from normal rabbits were soon activated markedly by lavage-procured immunoglobulin G, but not by lymphokines."}
{"id": "PMID:27461", "title": "Immuno-stimulation by a ribosomal vaccine associated with a bacterial cell wall adjuvant in humans.", "content": "We have studied a new vaccine of ribosomal nature associated with glycoprotein cell walls from Klebsiella pneumoniae which served as an immunoadjuvant. Thus vaccine was administered by the aerosol route to working men free of any important disease, especially of respiratory disease. A total of 104 men working for the Commissariat \u00e0 l'Energie Atomique, all volunteers, were randomly placed into two groups. During the first period, 51 patients (group I) were vaccinated three times a week during 5 weeks, and the second group was used as control. During the second period, which started on day 225, the control group received the vaccine, and the first group was revaccinated. Results of this experience show a significant difference in the immunity of the two groups. The specific antibodies increased with vaccination as illustrated by chi-square test (Yates correction), which corresponds to an independent probability equal to 0 (P = 0.5 X 10-4).", "contents": "Immuno-stimulation by a ribosomal vaccine associated with a bacterial cell wall adjuvant in humans. We have studied a new vaccine of ribosomal nature associated with glycoprotein cell walls from Klebsiella pneumoniae which served as an immunoadjuvant. Thus vaccine was administered by the aerosol route to working men free of any important disease, especially of respiratory disease. A total of 104 men working for the Commissariat \u00e0 l'Energie Atomique, all volunteers, were randomly placed into two groups. During the first period, 51 patients (group I) were vaccinated three times a week during 5 weeks, and the second group was used as control. During the second period, which started on day 225, the control group received the vaccine, and the first group was revaccinated. Results of this experience show a significant difference in the immunity of the two groups. The specific antibodies increased with vaccination as illustrated by chi-square test (Yates correction), which corresponds to an independent probability equal to 0 (P = 0.5 X 10-4)."}
{"id": "PMID:27463", "title": "Comparative investigation of the respiratory and cardiovascular effect of mepindolol, propranolol and pindolol in asthmatic patients.", "content": "In a controlled double-blind crossover trial of 5 mg mepindolol versus 80 mg propranolol, 15 mg pindolol or placebo given as single oral doses in 16 asthmatic patients, respiratory function and cardiovascular parameters were measured simultaneously. The doses chosen of the 3 active drugs were almost equipotent as shown by the similarity in the percentage fall in pulse rates at 2 hr after ingestion, although it was observed that propranolol had a different time course of effect from the 2 other beta blockers. The effect on respiratory function was marked for propranolol, with statistically significant falls in FEV1 and FEV3 at all times; mild for pindolol with lesser falls which were statistically significant only at nearly 3 hr post-ingestion; and intermediate for mepindolol. Mepindolol gave rise to a rapid and statistically significant fall in lying diastolic blood pressure compared to control values; the reductions in diastolic B. P. for propranolol or pindolol were not statistically significant compared to pretreatment control values.", "contents": "Comparative investigation of the respiratory and cardiovascular effect of mepindolol, propranolol and pindolol in asthmatic patients. In a controlled double-blind crossover trial of 5 mg mepindolol versus 80 mg propranolol, 15 mg pindolol or placebo given as single oral doses in 16 asthmatic patients, respiratory function and cardiovascular parameters were measured simultaneously. The doses chosen of the 3 active drugs were almost equipotent as shown by the similarity in the percentage fall in pulse rates at 2 hr after ingestion, although it was observed that propranolol had a different time course of effect from the 2 other beta blockers. The effect on respiratory function was marked for propranolol, with statistically significant falls in FEV1 and FEV3 at all times; mild for pindolol with lesser falls which were statistically significant only at nearly 3 hr post-ingestion; and intermediate for mepindolol. Mepindolol gave rise to a rapid and statistically significant fall in lying diastolic blood pressure compared to control values; the reductions in diastolic B. P. for propranolol or pindolol were not statistically significant compared to pretreatment control values."}
{"id": "PMID:27464", "title": "Assessment of beta-blocking activity of trimepranol in man.", "content": "The beta-blocking potency and the duration of action of trimepranol were measured in healthy volunteers using isoprenaline antagonism and reduction in exercise tachycardia. Based on isoprenaline antagonism, trimepranol was four times as potent as propranolol on a weight basis. The degree of beta blockade increased linearly with dose from 5 mg to 20 mg, excluding a dose-dependent first-pass metabolism in this dose range. There was a significnat correlation between plasma concentration and the effect of 14C-trimepranol on isoprenaline and exercise tests. The elimination half-life of trimepranol, calculated both on the basis of its effects and plasma concentrations, was approximately three to four hours. The beta blockade due to 10 or 20 mg of trimepranol was extended at least up to 12 hours following p.o. administration, based both on isoprenaline and exercise tests and on the effect of resting heart rate. Twice-a-day administration thus seems sufficient to provide a continuous beta blockade in the clinical use of trimepranol.", "contents": "Assessment of beta-blocking activity of trimepranol in man. The beta-blocking potency and the duration of action of trimepranol were measured in healthy volunteers using isoprenaline antagonism and reduction in exercise tachycardia. Based on isoprenaline antagonism, trimepranol was four times as potent as propranolol on a weight basis. The degree of beta blockade increased linearly with dose from 5 mg to 20 mg, excluding a dose-dependent first-pass metabolism in this dose range. There was a significnat correlation between plasma concentration and the effect of 14C-trimepranol on isoprenaline and exercise tests. The elimination half-life of trimepranol, calculated both on the basis of its effects and plasma concentrations, was approximately three to four hours. The beta blockade due to 10 or 20 mg of trimepranol was extended at least up to 12 hours following p.o. administration, based both on isoprenaline and exercise tests and on the effect of resting heart rate. Twice-a-day administration thus seems sufficient to provide a continuous beta blockade in the clinical use of trimepranol."}
{"id": "PMID:27465", "title": "Diazepam and halazepam in anxiety: some prognostic indicators.", "content": "A multiple step-search regression procedure was applied to data obtained with 37 diazepam and 42 halazepam treated anxious outpatients. Good treatment outcome was predicted for those patients who reported a more adequate family adjustment, the presence of precipitating stress, and who either had no prior psychotropic drug treatment, or if they had received such treatment, had experienced a good response. Probably of greatest interest to the practicing clinician was the observation that patients high in initial anxiety but low in initial interpersonal problems improved the most with both medications. Differential drug effects indicated halazepam to do particularly poorly in less anxious patients and in those patients given a good prognosis by the doctor. Diazepam response was much less affected by these variables. It is speculated that the excessive sedating effect of the daily halazepam dosage (160 mg/d) used in this study may explain these differential drug effects. In the dosages employed, namely, diazepam 20 mg/d and halazepam 160 mg/d, diazepam produced the more consistent anti-anxiety effects. The indication that halazepam 160 mg/d was more effective than diazepam 20 mg/d in the initially sicker patients, while of interest, is probably simply a dose-related phenomenon, indicating that diazepam 20 mg/d was too low a daily dosage for severely anxious patients, a fact well known by most clinicians.", "contents": "Diazepam and halazepam in anxiety: some prognostic indicators. A multiple step-search regression procedure was applied to data obtained with 37 diazepam and 42 halazepam treated anxious outpatients. Good treatment outcome was predicted for those patients who reported a more adequate family adjustment, the presence of precipitating stress, and who either had no prior psychotropic drug treatment, or if they had received such treatment, had experienced a good response. Probably of greatest interest to the practicing clinician was the observation that patients high in initial anxiety but low in initial interpersonal problems improved the most with both medications. Differential drug effects indicated halazepam to do particularly poorly in less anxious patients and in those patients given a good prognosis by the doctor. Diazepam response was much less affected by these variables. It is speculated that the excessive sedating effect of the daily halazepam dosage (160 mg/d) used in this study may explain these differential drug effects. In the dosages employed, namely, diazepam 20 mg/d and halazepam 160 mg/d, diazepam produced the more consistent anti-anxiety effects. The indication that halazepam 160 mg/d was more effective than diazepam 20 mg/d in the initially sicker patients, while of interest, is probably simply a dose-related phenomenon, indicating that diazepam 20 mg/d was too low a daily dosage for severely anxious patients, a fact well known by most clinicians."}
{"id": "PMID:27466", "title": "Drug interactions in psychiatry.", "content": "Since maintenance therapy with neuroleptics, lithium and tricyclic antidepressants may have to continue over extended periods of time, drug interactions between these psychotherapeutic agents and non-psychotropic treatments have become of practical clinical significance. In this paper some of the more common or important drug interactions between psychotherapeutic and non-psychotherapeutic agents are discussed.", "contents": "Drug interactions in psychiatry. Since maintenance therapy with neuroleptics, lithium and tricyclic antidepressants may have to continue over extended periods of time, drug interactions between these psychotherapeutic agents and non-psychotropic treatments have become of practical clinical significance. In this paper some of the more common or important drug interactions between psychotherapeutic and non-psychotherapeutic agents are discussed."}
{"id": "PMID:27468", "title": "Localization of beta receptors in the anterior segment of the rat eye by a fluorescent analogue of propranolol.", "content": "A fluorescent analogue of propranolol, 9-AAP, was injected intravenously in order to detect beta-adrenergic receptors in the anterior segment of the albino rat eye. Specific 9-AAP fluorescence was noted along cell membranes of the ciliary epithelium and to lesser extent in the walls of blood vessels in the ciliary processes and episclera at the limbus. The iris showed maximum 9-AAP binding in the region of the sphincter muscle. These data suggest that 9-AAP may label beta receptors in the anterior segment of the rat eye.", "contents": "Localization of beta receptors in the anterior segment of the rat eye by a fluorescent analogue of propranolol. A fluorescent analogue of propranolol, 9-AAP, was injected intravenously in order to detect beta-adrenergic receptors in the anterior segment of the albino rat eye. Specific 9-AAP fluorescence was noted along cell membranes of the ciliary epithelium and to lesser extent in the walls of blood vessels in the ciliary processes and episclera at the limbus. The iris showed maximum 9-AAP binding in the region of the sphincter muscle. These data suggest that 9-AAP may label beta receptors in the anterior segment of the rat eye."}
{"id": "PMID:27469", "title": "Light-evoked release of endogenous glycine into the perfused vitreous of the intact rat eye.", "content": "Glycine, a putative neurotransmitter, is released into the perfused vitreous of anesthetized pigmented rats when the eye is stimulated by intermittent flashes of bright light. Other amino acids do not show stimulated release. This result provides further evidence for the role of glycine as a neural transmitter in the retina.", "contents": "Light-evoked release of endogenous glycine into the perfused vitreous of the intact rat eye. Glycine, a putative neurotransmitter, is released into the perfused vitreous of anesthetized pigmented rats when the eye is stimulated by intermittent flashes of bright light. Other amino acids do not show stimulated release. This result provides further evidence for the role of glycine as a neural transmitter in the retina."}
{"id": "PMID:27471", "title": "Proximal renal tubular acidosis in metachromatic leukodystrophy.", "content": "A 2-year-old girl affected with the late infantile form of metachromatic leukodystrophy had a persistent and moderate metabolic acidosis. Renal functional studies demonstrated the presence of decreased tubular reabsorption of sodium, bicarbonate and some amino acids. Other tubular functions, including distal urinary acidification and concentrating mechanism were normal. Glomerular filtration rate was moderately decreased. Metachromatic inclusions were demonstrated along the nephron by histochemistry and electron microscopy. Tubular dysfunction in metachromatic leukodystrophy could have been overlooked until now given the severity of the neurological picture.", "contents": "Proximal renal tubular acidosis in metachromatic leukodystrophy. A 2-year-old girl affected with the late infantile form of metachromatic leukodystrophy had a persistent and moderate metabolic acidosis. Renal functional studies demonstrated the presence of decreased tubular reabsorption of sodium, bicarbonate and some amino acids. Other tubular functions, including distal urinary acidification and concentrating mechanism were normal. Glomerular filtration rate was moderately decreased. Metachromatic inclusions were demonstrated along the nephron by histochemistry and electron microscopy. Tubular dysfunction in metachromatic leukodystrophy could have been overlooked until now given the severity of the neurological picture."}
{"id": "PMID:27484", "title": "In vitro evaluations of monopolar intravascular oxygen sensors.", "content": "Intravascular PO2 electrodes of a commercially available design were tested in vitro to establish their characteristics and to further elucidate on their clinical usability. In addition, four different cathode-anode combinations, utilizing the same geometrical design, were evaluated to establich the best combination. Au-Ag/AgCl exhibited the best characteristics as verified by the evaluation of stabilization time, sensitivity and reproducibility of the response, response time, linearity, drift, effects of temperature, flow, and pH, and the useful life of the sensors. Even though the Au-Ag/AgCl combination exhibited the best characteristics, it fell far below clinically recommended criteria for continuous monitoring of less than 10 Torr/24 h.", "contents": "In vitro evaluations of monopolar intravascular oxygen sensors. Intravascular PO2 electrodes of a commercially available design were tested in vitro to establish their characteristics and to further elucidate on their clinical usability. In addition, four different cathode-anode combinations, utilizing the same geometrical design, were evaluated to establich the best combination. Au-Ag/AgCl exhibited the best characteristics as verified by the evaluation of stabilization time, sensitivity and reproducibility of the response, response time, linearity, drift, effects of temperature, flow, and pH, and the useful life of the sensors. Even though the Au-Ag/AgCl combination exhibited the best characteristics, it fell far below clinically recommended criteria for continuous monitoring of less than 10 Torr/24 h."}
{"id": "PMID:27485", "title": "Regulation of intracellular pH in lungs and other tissues during hypercapnia.", "content": "Using a 14C-labeled DMO, 36Cl and 3H method, we have determined the in vivo buffering capacity of lung, kidney, heart, skeletal muscle, and extracellular fluid (ECF) of guinea pigs during hypercapnia (FICO2 = 0.15). After 1 days' exposureto 15% CO2, both the relative CO2 buffer values (delta HCO3/deltapH) and the \"%pH regulation\" were lung greater than kidney greater than heart greater than ECF greater than skeletal muscle. For lung tissue the intracellular pH was significantly decreased only during acute (8 h) hypercapnia and had completely returned to control values after 7 days with arterial PCO2 congruent to 122 Torr. Kidney and cardiac muscle also showed ca. 100% regulation of pH at 7 days, whereas skeletal muscle and ECF showed only 80 and 70% pH regulation, respectively. The results are discussed with respect to the important (and pH-dependent) metabolic functions of the lung and kidney.", "contents": "Regulation of intracellular pH in lungs and other tissues during hypercapnia. Using a 14C-labeled DMO, 36Cl and 3H method, we have determined the in vivo buffering capacity of lung, kidney, heart, skeletal muscle, and extracellular fluid (ECF) of guinea pigs during hypercapnia (FICO2 = 0.15). After 1 days' exposureto 15% CO2, both the relative CO2 buffer values (delta HCO3/deltapH) and the \"%pH regulation\" were lung greater than kidney greater than heart greater than ECF greater than skeletal muscle. For lung tissue the intracellular pH was significantly decreased only during acute (8 h) hypercapnia and had completely returned to control values after 7 days with arterial PCO2 congruent to 122 Torr. Kidney and cardiac muscle also showed ca. 100% regulation of pH at 7 days, whereas skeletal muscle and ECF showed only 80 and 70% pH regulation, respectively. The results are discussed with respect to the important (and pH-dependent) metabolic functions of the lung and kidney."}
{"id": "PMID:27486", "title": "Red cell oxygen affinity in fetal sheep: role of 2,3-DPG and adult hemoglobin.", "content": "Studies were carried out during fetal life in sheep to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the switchover to adult hemoglobin synthesis in regulating the position of the fetal red cell oxygen-affinity curve in utero. Adult hemoglobin first appeared near 120 days of gestation. The mean oxygen tension at which hemoglobin is half saturated (P50) prior to 120 days of gestation remained constant at 13.9 +/- 0.3 (SD) Torr and then increased gradually as gestation continued, reaching 19 Torr at term. During the interval of fetal life studied, the level of DPG was 4.43 +/- 1.63 (SD) micromol/g Hb and the deltapH between plasma and red blood cells was 0.227 +/- 0.038 (SD); neither was affected by gestational age. The decrease in the red cell oxygen affinity after 120 days of gestation ocrrelated with the amount of adult hemoglobin present in the fetus (r = 0.78; P less than 0.001). This decrease can be attributed only to the amount of the adult-type hemoglobin present, and not to DPG, or to changes in the deltapH between plasma and red blood cells, because both remained stable during the last trimester.", "contents": "Red cell oxygen affinity in fetal sheep: role of 2,3-DPG and adult hemoglobin. Studies were carried out during fetal life in sheep to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the switchover to adult hemoglobin synthesis in regulating the position of the fetal red cell oxygen-affinity curve in utero. Adult hemoglobin first appeared near 120 days of gestation. The mean oxygen tension at which hemoglobin is half saturated (P50) prior to 120 days of gestation remained constant at 13.9 +/- 0.3 (SD) Torr and then increased gradually as gestation continued, reaching 19 Torr at term. During the interval of fetal life studied, the level of DPG was 4.43 +/- 1.63 (SD) micromol/g Hb and the deltapH between plasma and red blood cells was 0.227 +/- 0.038 (SD); neither was affected by gestational age. The decrease in the red cell oxygen affinity after 120 days of gestation ocrrelated with the amount of adult hemoglobin present in the fetus (r = 0.78; P less than 0.001). This decrease can be attributed only to the amount of the adult-type hemoglobin present, and not to DPG, or to changes in the deltapH between plasma and red blood cells, because both remained stable during the last trimester."}
{"id": "PMID:27489", "title": "Management an experimental approach.", "content": "An experimental teaching procedure was devised and tested for integrating the nursing process, nursing care plans, the research process and management principals. The integration defined as the problem oriented process (POP) was tested with 16 students over two semesters. The results indicated that the POP was a successful integration that aided the student in \"getting it all together.\" As one of the students put it: This experience will give future students, as it did me, a better understanding of how research is best utilized. The students can use almost all their past learning experiences, bringing it all together in one situation. He (the student) can use his communication skills to detect a problem, his research skills to design  planned intervention and evaluation and his interpersonal skills to measure his effectiveness as a change agent. Finally, he can use his nursing skills and knowledge of pathophysiology in a setting most like what he will find upon graduation.", "contents": "Management an experimental approach. An experimental teaching procedure was devised and tested for integrating the nursing process, nursing care plans, the research process and management principals. The integration defined as the problem oriented process (POP) was tested with 16 students over two semesters. The results indicated that the POP was a successful integration that aided the student in \"getting it all together.\" As one of the students put it: This experience will give future students, as it did me, a better understanding of how research is best utilized. The students can use almost all their past learning experiences, bringing it all together in one situation. He (the student) can use his communication skills to detect a problem, his research skills to design  planned intervention and evaluation and his interpersonal skills to measure his effectiveness as a change agent. Finally, he can use his nursing skills and knowledge of pathophysiology in a setting most like what he will find upon graduation."}
{"id": "PMID:27490", "title": "On \"problems\" with integrated curricula in nursing.", "content": "Curriculum development is many things; it is the study of impact on students, a process through which faculty are moving. It usually does not represent a final decision- like all issues in higher education it is altered as different people and issues arise. The integrated curriculum movement in nursing, while a seminal change, has in a way been like a shadow- incompletely described with lack of clarity about base for comparison. It seems to have become the mode for many schools to develop their own conceptual frameworks and curricular plans. While adaptation to the local setting is expected, one must question how much of the total development effort is necessary and due in part to lack of fully developed curriculum models and dissemination and not building systematically toward improvement in the field. In such a situation we all may be making the same mistakes. If these identified \"problems\" are indeed just that, they all are amenable to correction. Each solution will require hard conceptual work.", "contents": "On \"problems\" with integrated curricula in nursing. Curriculum development is many things; it is the study of impact on students, a process through which faculty are moving. It usually does not represent a final decision- like all issues in higher education it is altered as different people and issues arise. The integrated curriculum movement in nursing, while a seminal change, has in a way been like a shadow- incompletely described with lack of clarity about base for comparison. It seems to have become the mode for many schools to develop their own conceptual frameworks and curricular plans. While adaptation to the local setting is expected, one must question how much of the total development effort is necessary and due in part to lack of fully developed curriculum models and dissemination and not building systematically toward improvement in the field. In such a situation we all may be making the same mistakes. If these identified \"problems\" are indeed just that, they all are amenable to correction. Each solution will require hard conceptual work."}
{"id": "PMID:27492", "title": "Seduction and the hospitalized person.", "content": "Seductive behavior seen in the convalescent individual is generally a signal that the patient is in the process of assessment. It is not a social invitation to sexual activity. The patient is merely trying to reassess his situation after having experienced an illness, injury or surgery. Nurses have an obligation to be informed regarding the effects of illness on sexuality, and an obligation to recognize the patient's seductive signals. Nurses need to recognize the mechanics of seductive behavior and be able to qualify the behavior in order to help the patient express his/her concerns during convalescence. Finally, nurses have an obligation to discover or create referral sources in their local area where patients may seek help with their altered sexual function, should that be warranted.", "contents": "Seduction and the hospitalized person. Seductive behavior seen in the convalescent individual is generally a signal that the patient is in the process of assessment. It is not a social invitation to sexual activity. The patient is merely trying to reassess his situation after having experienced an illness, injury or surgery. Nurses have an obligation to be informed regarding the effects of illness on sexuality, and an obligation to recognize the patient's seductive signals. Nurses need to recognize the mechanics of seductive behavior and be able to qualify the behavior in order to help the patient express his/her concerns during convalescence. Finally, nurses have an obligation to discover or create referral sources in their local area where patients may seek help with their altered sexual function, should that be warranted."}
{"id": "PMID:27494", "title": "1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides.", "content": "1-N HAPA gentamicin B is a new aminoglycoside active against most Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. Among 504 clinical isolates at a concentration of 12.5 microgram/ml all Staph. aureus, Escherichia coli, Klebsiella, Enterobacter, Proteus rettgeri, Providencia and 78% of Pseudomonas, 86% of Proteus morganii were inhibited. Like other aminoglycosides, the activity was greatest at an alkaline ph and reduced by high cations concentrations. 1-N HAPA gentamicin B was equal in activity to amikacin against both gentamicin-sensitive and resistant isolates. It inhibited bacteria containing many of the aminoglycoside inactivating enzymes. When combined with carbenicillin it inhibited in a synergistic manner many Gram-negative bacteria, particularly Pseudomonas and Serratia.", "contents": "1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides. 1-N HAPA gentamicin B is a new aminoglycoside active against most Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. Among 504 clinical isolates at a concentration of 12.5 microgram/ml all Staph. aureus, Escherichia coli, Klebsiella, Enterobacter, Proteus rettgeri, Providencia and 78% of Pseudomonas, 86% of Proteus morganii were inhibited. Like other aminoglycosides, the activity was greatest at an alkaline ph and reduced by high cations concentrations. 1-N HAPA gentamicin B was equal in activity to amikacin against both gentamicin-sensitive and resistant isolates. It inhibited bacteria containing many of the aminoglycoside inactivating enzymes. When combined with carbenicillin it inhibited in a synergistic manner many Gram-negative bacteria, particularly Pseudomonas and Serratia."}
{"id": "PMID:27495", "title": "Macrolide antibiotics M-4365 produced by Micromonospora. III. In vitro antimicrobial activity of antibiotic M-4365G2 (de-epoxy rosamicin).", "content": "Antibiotic M-4365G2 (de-epoxy rosamicin) produced by Micromonospora capillata MCRL 0940 is a new basic 16-membered macrolide antibiotic with activity equal to or superior to erythromycin and josamycin against Gram-positive bacteria. Of interest are the high degree of activity against Gram-negative bacilli and mycoplasmas, and striking inhibitory effects against indole-producing Proteus spp. Bactericidal activity of M-4365G2 is also to be noticed.", "contents": "Macrolide antibiotics M-4365 produced by Micromonospora. III. In vitro antimicrobial activity of antibiotic M-4365G2 (de-epoxy rosamicin). Antibiotic M-4365G2 (de-epoxy rosamicin) produced by Micromonospora capillata MCRL 0940 is a new basic 16-membered macrolide antibiotic with activity equal to or superior to erythromycin and josamycin against Gram-positive bacteria. Of interest are the high degree of activity against Gram-negative bacilli and mycoplasmas, and striking inhibitory effects against indole-producing Proteus spp. Bactericidal activity of M-4365G2 is also to be noticed."}
{"id": "PMID:27498", "title": "Control of ammonium assimilation in Rhizobium 32H1.", "content": "The symbiotic, nitrogen-fixing bacterium Rhizobium sp. 32H1 is a specialized ammonium producer during symbiosis. However, during free-living growth, Rhizobium 32H1 assimilates ammonium very poorly. Two pathways of ammonium assimilation exist in enteric bacteria. One is mediated by glutamate dehydrogenase, and the other is mediated by glutamine synthetase-glutamate synthase. The former pathway is altogether inoperative in Rhizobium 32H1; the latter pathway operates at a slow rate and is under strict negative control by ammonium itself. Rhizobium 32H1 glutamine synthetase activity is modulated by both repression-derepression and reversible adenylylation. For a biochemical process lacking an alternative pathway, such a regulatory pattern exacerbates the very process. This suggests that Rhizobium 32H1 restricts its own ammonium assimilation to maximize the contribution of fixed nitrogen to the host plant during symbiosis.", "contents": "Control of ammonium assimilation in Rhizobium 32H1. The symbiotic, nitrogen-fixing bacterium Rhizobium sp. 32H1 is a specialized ammonium producer during symbiosis. However, during free-living growth, Rhizobium 32H1 assimilates ammonium very poorly. Two pathways of ammonium assimilation exist in enteric bacteria. One is mediated by glutamate dehydrogenase, and the other is mediated by glutamine synthetase-glutamate synthase. The former pathway is altogether inoperative in Rhizobium 32H1; the latter pathway operates at a slow rate and is under strict negative control by ammonium itself. Rhizobium 32H1 glutamine synthetase activity is modulated by both repression-derepression and reversible adenylylation. For a biochemical process lacking an alternative pathway, such a regulatory pattern exacerbates the very process. This suggests that Rhizobium 32H1 restricts its own ammonium assimilation to maximize the contribution of fixed nitrogen to the host plant during symbiosis."}
{"id": "PMID:27499", "title": "Purification and properties of a second enzyme catalyzing the splitting of carbon-mercury linkages from mercury-resistant Pseudomonas K-62.", "content": "An enzyme (splitting enzyme 2) which catalyzes the splitting of carbon-mercury linkage of arylmercury compounds was found in extracts of mercury-resistant Pseudomonas K-62. This enzyme was purified about 725-fold by treatment with streptomycin, precipitation with ammonium sulfate, and successive chromatography on Sephadex G-75 and diethylaminoethyl-cellulose. A purified preparation of the enzyme showed a single band in electrophoresis either on polyacrylamide or sodium dodecyl sulfate-containing polyacrylamide gels. The molecular weight of the enzyme was estimated to be 20,000 (determined by Sephadex G-75 gel filtration) 17,000 (determined by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis). The enzyme showed a Km of 180 micron and a Vmax of 3.1 mumol/min per mg for p-chloromercuribenzoic acid and a Km of 250 micron and a Vmax of 20 mumol/min per mg for phenylmercuric acetate. The optimum temperature and pH for the reaction were 40 degrees C and 5.0, respectively.", "contents": "Purification and properties of a second enzyme catalyzing the splitting of carbon-mercury linkages from mercury-resistant Pseudomonas K-62. An enzyme (splitting enzyme 2) which catalyzes the splitting of carbon-mercury linkage of arylmercury compounds was found in extracts of mercury-resistant Pseudomonas K-62. This enzyme was purified about 725-fold by treatment with streptomycin, precipitation with ammonium sulfate, and successive chromatography on Sephadex G-75 and diethylaminoethyl-cellulose. A purified preparation of the enzyme showed a single band in electrophoresis either on polyacrylamide or sodium dodecyl sulfate-containing polyacrylamide gels. The molecular weight of the enzyme was estimated to be 20,000 (determined by Sephadex G-75 gel filtration) 17,000 (determined by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis). The enzyme showed a Km of 180 micron and a Vmax of 3.1 mumol/min per mg for p-chloromercuribenzoic acid and a Km of 250 micron and a Vmax of 20 mumol/min per mg for phenylmercuric acetate. The optimum temperature and pH for the reaction were 40 degrees C and 5.0, respectively."}
{"id": "PMID:27500", "title": "Alcohol dehydrogenases from a facultative methylotrophic bacterium.", "content": "Alcohol-oxidizing enzymes of the facultative methylotroph PAR were investigated after growth of the bacteria on methanol and ethanol. During methanol growth only a phenazine methosulfate-linked alcohol dehydrogenase was detected. This enzyme had broad specificity for primary alcohols and was also capable of oxidation of secondary alcohols. It had a molecular weight of 112,000, was composed of two subunits of equal molecular weight, and showed an absolute requirement for ammonium ion for activation. During ethanol growth this enzyme was absent and was replaced by a typical nicotinamide adenine dinucleotide-linked alcohol dehydrogenase of molecular weight 150,000. The latter enzyme also had broad specificity but could not oxidize methanol. This enzyme was not found during methanol growth. These data show that the organism has two distinctly separate mechanisms for oxidation of alcohols.", "contents": "Alcohol dehydrogenases from a facultative methylotrophic bacterium. Alcohol-oxidizing enzymes of the facultative methylotroph PAR were investigated after growth of the bacteria on methanol and ethanol. During methanol growth only a phenazine methosulfate-linked alcohol dehydrogenase was detected. This enzyme had broad specificity for primary alcohols and was also capable of oxidation of secondary alcohols. It had a molecular weight of 112,000, was composed of two subunits of equal molecular weight, and showed an absolute requirement for ammonium ion for activation. During ethanol growth this enzyme was absent and was replaced by a typical nicotinamide adenine dinucleotide-linked alcohol dehydrogenase of molecular weight 150,000. The latter enzyme also had broad specificity but could not oxidize methanol. This enzyme was not found during methanol growth. These data show that the organism has two distinctly separate mechanisms for oxidation of alcohols."}
{"id": "PMID:27501", "title": "Glycolipids stimulate DNA polymerase activity in a DNA-membrane fraction and in a partially purified polymerase system extracted from pneumococci.", "content": "We have assayed the ability of various lipids to affect DNA polymerases activity in a DNA-membrane complex extracted from Streptococcus pneumoniae by the Sarkosyl-M-band technique. In addition, to determine which DNA polymerases were affected by the lipids, we partially purified three DNA polymerase activities from cell lysates, the first such demonstration outside of Escherichia coli and Bacillus subtilis. Glycolipids are unique among polar lipids in stimulating the rate and extent of DNA polymerase activity in M-bands and in Sarkosyl lysates from which the M-band is derived. It appears that they exert this stimulatory effect, in part, by removing (neutralizing) detergent molecules which act as inhibitors, as well as by substituting for the detergent, thereby creating a favorable environment for the polymerases involved in DNA synthesis. That the stimulatory effect is not simply a detoxification of the detergent was shown by two observations. One, phospholipids, although interacting with Sarkosyl and therefore \"potentially\" capable of detoxifying the system, did not stimulate DNA polymerase activity in vitro. Two, glycolipids were capable of stimulating the activity of at least two DNA polymerases partially purified from cell lysates in the absence of any Sarkosyl. The stimulatory effect was greater for a polymerase that had four characteristics similar to those observed with polymerase III in other organisms.", "contents": "Glycolipids stimulate DNA polymerase activity in a DNA-membrane fraction and in a partially purified polymerase system extracted from pneumococci. We have assayed the ability of various lipids to affect DNA polymerases activity in a DNA-membrane complex extracted from Streptococcus pneumoniae by the Sarkosyl-M-band technique. In addition, to determine which DNA polymerases were affected by the lipids, we partially purified three DNA polymerase activities from cell lysates, the first such demonstration outside of Escherichia coli and Bacillus subtilis. Glycolipids are unique among polar lipids in stimulating the rate and extent of DNA polymerase activity in M-bands and in Sarkosyl lysates from which the M-band is derived. It appears that they exert this stimulatory effect, in part, by removing (neutralizing) detergent molecules which act as inhibitors, as well as by substituting for the detergent, thereby creating a favorable environment for the polymerases involved in DNA synthesis. That the stimulatory effect is not simply a detoxification of the detergent was shown by two observations. One, phospholipids, although interacting with Sarkosyl and therefore \"potentially\" capable of detoxifying the system, did not stimulate DNA polymerase activity in vitro. Two, glycolipids were capable of stimulating the activity of at least two DNA polymerases partially purified from cell lysates in the absence of any Sarkosyl. The stimulatory effect was greater for a polymerase that had four characteristics similar to those observed with polymerase III in other organisms."}
{"id": "PMID:27503", "title": "EPR investigation of the Mn(II) binding sites in glutamine synthetase (Escherichia coli W). II. Intermediate-affinity binding sites.", "content": "The nature of the intermediate-affinity (n2) Mn(II) binding sites in glutamine synthetase [EC 6.3.1.2] has been studied as a function of adenylylation in a variety of enzyme-metal complexes by EPR. In the absence of nucleotide the n2 Mn(II) environment is nearly isotropic, the Mn(II) bonds are highly ionic, and the interaction distance R greater than or equal to 12-14 A. Nucleotide binding at the n2 Mn(II) site renders the n2 Mn(II) signal unobservable and causes a reduction in signal amplitude (approximately 30%) and line broadening (approximately 6 G) at the high-affinity (n1) Mn(II) site. This behavior indicates that nucleotide binding induces a conformational change in the enzyme which brings the previously distant n1 and n2 sites into closer proximity (R less than or equal to 8-11 A), possibly for the purpose of activating the nucleotide for direct phosphoryl transfer to L-glutamate. In line with this suggestion, the broad, unresolved resonances in complexes containing both L-methionine SR-sulfoximine (MSOX) and nucleotide may result from the phosphorylation of MSOX. The n2 Mn(II) site is not affected by adenylylation in all the enzyme-metal complexes studied, which suggests that the regulatory effects of adenylylation may only act at the n1 Mn(II) sites.", "contents": "EPR investigation of the Mn(II) binding sites in glutamine synthetase (Escherichia coli W). II. Intermediate-affinity binding sites. The nature of the intermediate-affinity (n2) Mn(II) binding sites in glutamine synthetase [EC 6.3.1.2] has been studied as a function of adenylylation in a variety of enzyme-metal complexes by EPR. In the absence of nucleotide the n2 Mn(II) environment is nearly isotropic, the Mn(II) bonds are highly ionic, and the interaction distance R greater than or equal to 12-14 A. Nucleotide binding at the n2 Mn(II) site renders the n2 Mn(II) signal unobservable and causes a reduction in signal amplitude (approximately 30%) and line broadening (approximately 6 G) at the high-affinity (n1) Mn(II) site. This behavior indicates that nucleotide binding induces a conformational change in the enzyme which brings the previously distant n1 and n2 sites into closer proximity (R less than or equal to 8-11 A), possibly for the purpose of activating the nucleotide for direct phosphoryl transfer to L-glutamate. In line with this suggestion, the broad, unresolved resonances in complexes containing both L-methionine SR-sulfoximine (MSOX) and nucleotide may result from the phosphorylation of MSOX. The n2 Mn(II) site is not affected by adenylylation in all the enzyme-metal complexes studied, which suggests that the regulatory effects of adenylylation may only act at the n1 Mn(II) sites."}
{"id": "PMID:27504", "title": "Use of fluorescamine-labeled casein as a substrate for assay of proteinases.", "content": "Conditions have been investigated for the use of fluorescamine-labeled casein as a substrate for fluorometric assay of proteinases. Fluorescamine-labeled casein can be prepared simply by mixing solutions of casein and fluorescamine at pH 8.0 and used without removal of the excess reagent or its hydrolysis product. The fluorescence of the labeled casein and its enzymatic digest is moderately stable in the range of pH 7.0 to 10.0. Activities can be determined by measuring the fluorescence of the hydrolysis products soluble in 0.1 M trichloro acetic acid solution at pH 4.0 after adjusting the pH of the acid-soluble fraction to 7.7. This method is suited for assay of proteinases active at neutral to slightly alkaline pH values, and is capable of quantitating about 0.05 microgram of trypsin or 0.5 microgram of alpha-chymotrypsin or papain. The assay can be done in the presence of large amounts of contaminating amino acid, protein and/or exopeptidases which may interfere with the ordinary assay of proteinases.", "contents": "Use of fluorescamine-labeled casein as a substrate for assay of proteinases. Conditions have been investigated for the use of fluorescamine-labeled casein as a substrate for fluorometric assay of proteinases. Fluorescamine-labeled casein can be prepared simply by mixing solutions of casein and fluorescamine at pH 8.0 and used without removal of the excess reagent or its hydrolysis product. The fluorescence of the labeled casein and its enzymatic digest is moderately stable in the range of pH 7.0 to 10.0. Activities can be determined by measuring the fluorescence of the hydrolysis products soluble in 0.1 M trichloro acetic acid solution at pH 4.0 after adjusting the pH of the acid-soluble fraction to 7.7. This method is suited for assay of proteinases active at neutral to slightly alkaline pH values, and is capable of quantitating about 0.05 microgram of trypsin or 0.5 microgram of alpha-chymotrypsin or papain. The assay can be done in the presence of large amounts of contaminating amino acid, protein and/or exopeptidases which may interfere with the ordinary assay of proteinases."}
{"id": "PMID:27506", "title": "Heat activation of rat liver acetyl-CoA carboxylase in vitro.", "content": "Acetyl-CoA carboxylase in rat liver homogenates was activated in vitro in a time- and temperature-dependent manner. The activity of acetyl-CoA carboxylase in rat liver preparations was determined in a 1-min assay to preclude the possibility of citrate activation of the enzyme during the assay period. Activation of the enzyme occurred more rapidly in liver preparations continuously maintained at ambient or greater temperatures than in homogenates of liver which had been chilled. High speed supernatant (105,000 X g, 60 min) did not heat-activate, and reconstitution of the heat-activatable 27,000 X g, 20-min, fraction by recombining the high speed pellet with the high speed supernatant only partially restored the heat activatability. Elution of the 105,000 X g supernatant from Sephadex G-25 resulted in an enzyme preparation which was heat-activatable. Addition of boiled 105,000 X g supernatant to the Sephadex G-25-treated enzyme again prevented heat activation. Dilution of the enzyme 5-fold did not prevent heat activation.", "contents": "Heat activation of rat liver acetyl-CoA carboxylase in vitro. Acetyl-CoA carboxylase in rat liver homogenates was activated in vitro in a time- and temperature-dependent manner. The activity of acetyl-CoA carboxylase in rat liver preparations was determined in a 1-min assay to preclude the possibility of citrate activation of the enzyme during the assay period. Activation of the enzyme occurred more rapidly in liver preparations continuously maintained at ambient or greater temperatures than in homogenates of liver which had been chilled. High speed supernatant (105,000 X g, 60 min) did not heat-activate, and reconstitution of the heat-activatable 27,000 X g, 20-min, fraction by recombining the high speed pellet with the high speed supernatant only partially restored the heat activatability. Elution of the 105,000 X g supernatant from Sephadex G-25 resulted in an enzyme preparation which was heat-activatable. Addition of boiled 105,000 X g supernatant to the Sephadex G-25-treated enzyme again prevented heat activation. Dilution of the enzyme 5-fold did not prevent heat activation."}
{"id": "PMID:27507", "title": "Transglutaminase-catalyzed cross-linking through diamines and polyamines.", "content": "Transglutaminases were found to catalyze the formation of cross-links between peptide chains by means of a transfer reaction between the carboxamide group of a glutamine residue in each chain and both primary amino groups of a diamine or a polyamine. Production of this heretofore undescribed linkage by guinea pig liver transglutaminase was demonstrated by the use of high performance liquid chromatography in a model system using glutamine peptide derivatives and a variety of diamines and polyamines. Evidence for intermolecular cross-linking through polyamines with both the liver enzyme and thrombin-activated human plasma blood coagulation factor XIII was obtained by the use of a guanidinated derivative of beta-casein.", "contents": "Transglutaminase-catalyzed cross-linking through diamines and polyamines. Transglutaminases were found to catalyze the formation of cross-links between peptide chains by means of a transfer reaction between the carboxamide group of a glutamine residue in each chain and both primary amino groups of a diamine or a polyamine. Production of this heretofore undescribed linkage by guinea pig liver transglutaminase was demonstrated by the use of high performance liquid chromatography in a model system using glutamine peptide derivatives and a variety of diamines and polyamines. Evidence for intermolecular cross-linking through polyamines with both the liver enzyme and thrombin-activated human plasma blood coagulation factor XIII was obtained by the use of a guanidinated derivative of beta-casein."}
{"id": "PMID:27508", "title": "Direct inhibition of tyrosine hydroxylase activity by catechol estrogens.", "content": "Catechol estrogens, the 2-hydroxylated metabolites of estrogens, recently shown to be formed in brain, inhibit tyrosine hydroxylase, the enzyme that catalyzes the pivotal step in the biosynthesis of the neurotransmitters dopamine and norepinephrine. The nature of the inhibition is by competition with the pterin cofactor and thus resembles feedback inhibition of the enzyme by catecholamines.", "contents": "Direct inhibition of tyrosine hydroxylase activity by catechol estrogens. Catechol estrogens, the 2-hydroxylated metabolites of estrogens, recently shown to be formed in brain, inhibit tyrosine hydroxylase, the enzyme that catalyzes the pivotal step in the biosynthesis of the neurotransmitters dopamine and norepinephrine. The nature of the inhibition is by competition with the pterin cofactor and thus resembles feedback inhibition of the enzyme by catecholamines."}
{"id": "PMID:27511", "title": "Determination of glucose oxidase oxidation-reduction potentials and the oxygen reactivity of fully reduced and semiquinoid forms.", "content": "The oxidation-reduction potential values for the two electron transfers to glucose oxidase were obtained at pH 5.3, where the neutral radical is the stable form, and at pH 9.3, where the anion radical is the stable form. The midpoint potentials at 25 degrees were: pH 5.3 EFl1ox + e- H+ equilibrium EFlH. Em1 = -0.063 +/- 0.011 V EFlH. + e- + H+ equilibrium EFlredH2 Em2 = -0.065 +/- 0.007 V pH 9.3 EFlox + e- EFi- Em1 = -0.200 +/- 0.010 V EFi- + e- + H+ equilibrium EFlredH- Em2 = -0.240 +/- 0.005 V All potentials were measured versus the standard hydrogen electrode (SHE). The potentials indicated that glucose oxidase radicals are stabilized by kinetic factors and not by thermodynamic energy barriers. The pK for the glucose oxidase radical was 7.28 from dead time stopped flow measurements and the extinction coefficient of the neutral semiquinone was 4140 M-1 cm-1 at 570 nm. Both radical forms reacted with oxygen in a second order fashion. The rate at 25 degrees for the neutral semiquinone was 1.4 X 10(4) M-1 s-1; that for the anion radical was 3.5 X 10(4) M-1 s-1. The rate of oxidation of the neutral radical changed by a factor of 9 for a temperature difference of 22 degrees. For the anion radical, the oxidation rate changed by a factor of 6 for a 22 degrees change in temperature. We studied the oxygen reactivity of the 2-electron reduced form of the enzyme over a wide wavelength range and failed to detect either oxygenated flavin derivatives or semiquinoid forms as intermediates. The rate of reoxidation of fully reduced glucose oxidase at pH 9.3 was dependent on ionic strength.", "contents": "Determination of glucose oxidase oxidation-reduction potentials and the oxygen reactivity of fully reduced and semiquinoid forms. The oxidation-reduction potential values for the two electron transfers to glucose oxidase were obtained at pH 5.3, where the neutral radical is the stable form, and at pH 9.3, where the anion radical is the stable form. The midpoint potentials at 25 degrees were: pH 5.3 EFl1ox + e- H+ equilibrium EFlH. Em1 = -0.063 +/- 0.011 V EFlH. + e- + H+ equilibrium EFlredH2 Em2 = -0.065 +/- 0.007 V pH 9.3 EFlox + e- EFi- Em1 = -0.200 +/- 0.010 V EFi- + e- + H+ equilibrium EFlredH- Em2 = -0.240 +/- 0.005 V All potentials were measured versus the standard hydrogen electrode (SHE). The potentials indicated that glucose oxidase radicals are stabilized by kinetic factors and not by thermodynamic energy barriers. The pK for the glucose oxidase radical was 7.28 from dead time stopped flow measurements and the extinction coefficient of the neutral semiquinone was 4140 M-1 cm-1 at 570 nm. Both radical forms reacted with oxygen in a second order fashion. The rate at 25 degrees for the neutral semiquinone was 1.4 X 10(4) M-1 s-1; that for the anion radical was 3.5 X 10(4) M-1 s-1. The rate of oxidation of the neutral radical changed by a factor of 9 for a temperature difference of 22 degrees. For the anion radical, the oxidation rate changed by a factor of 6 for a 22 degrees change in temperature. We studied the oxygen reactivity of the 2-electron reduced form of the enzyme over a wide wavelength range and failed to detect either oxygenated flavin derivatives or semiquinoid forms as intermediates. The rate of reoxidation of fully reduced glucose oxidase at pH 9.3 was dependent on ionic strength."}
{"id": "PMID:27512", "title": "Dependence of the catalytic activity of papain on the ionization of two acidic groups.", "content": "The pH dependence of kcat/Km for the papain-catalyzed hydrolysis of ethyl hippurate, N-alpha-benzoyl-L-citrulline methyl ester, and the p-nitroanilide, amide, and ethyl ester derivatives of N-alpha-benzoyl-L-arginine was determined below pH 6.4. The value of kcat/Km was observed to be modulated by two acid ionizations rather than a single ionization as previously believed. For the five substrates studied, the average pK values for the two ionizations are 3.78 +/- 0.2 and 3.95 +/- 0.1 at T/2 0.3, 25 degrees C. The observation that similar pK values were obtained with different substrates was taken as evidence that the kinetically determined pK values are close in value to true macroscopic ionization constants for ionization of groups on the free enzyme.", "contents": "Dependence of the catalytic activity of papain on the ionization of two acidic groups. The pH dependence of kcat/Km for the papain-catalyzed hydrolysis of ethyl hippurate, N-alpha-benzoyl-L-citrulline methyl ester, and the p-nitroanilide, amide, and ethyl ester derivatives of N-alpha-benzoyl-L-arginine was determined below pH 6.4. The value of kcat/Km was observed to be modulated by two acid ionizations rather than a single ionization as previously believed. For the five substrates studied, the average pK values for the two ionizations are 3.78 +/- 0.2 and 3.95 +/- 0.1 at T/2 0.3, 25 degrees C. The observation that similar pK values were obtained with different substrates was taken as evidence that the kinetically determined pK values are close in value to true macroscopic ionization constants for ionization of groups on the free enzyme."}
{"id": "PMID:27515", "title": "Multiple phosphorylation of acetyl-CoA carboxylase in chick liver cells. A cyclic AMP-independent process.", "content": "When chick liver cells in monolayer culture were incubated with 32Pi in the presence of insulin, acetyl-CoA carboxylase became extensively labeled with 32Pi reaching a stoichiometry of 9 to 10 mol of phosphoryl group per mol of 240,000-dalton enzyme subunit. The covalently bound phosphate was found to be metabolically labile, turning over with a t1/2 of approximately 2 h (enzyme t1/2 approximately equal to 24 h). Addition of Bt2cAMP altered neither the rate nor extent of phosphorylation. Contrary to other reports, the fully phosphorylated acetyl-CoA carboxylase appears to be catalytically active.", "contents": "Multiple phosphorylation of acetyl-CoA carboxylase in chick liver cells. A cyclic AMP-independent process. When chick liver cells in monolayer culture were incubated with 32Pi in the presence of insulin, acetyl-CoA carboxylase became extensively labeled with 32Pi reaching a stoichiometry of 9 to 10 mol of phosphoryl group per mol of 240,000-dalton enzyme subunit. The covalently bound phosphate was found to be metabolically labile, turning over with a t1/2 of approximately 2 h (enzyme t1/2 approximately equal to 24 h). Addition of Bt2cAMP altered neither the rate nor extent of phosphorylation. Contrary to other reports, the fully phosphorylated acetyl-CoA carboxylase appears to be catalytically active."}
{"id": "PMID:27516", "title": "Metabolism of prostacyclin in blood vessels.", "content": "The activity of 15-hydroxyprostaglandin dehydrogenase has been shown to be high in both mesenteric arteries and veins; the present study suggests that it may be responsible for the inactivation of prostacyclin (PGI2). The cytoplasmic fractions of bovine mesenteric arteries and veins were incubated with radiolabeled PGI2 in the presence of NAD+ or NADP+. The substrate was rapidly converted to a product, which was isolated and identified as 6,15-diketo prostaglandin F1alpha, (6,15-diketo-PGF1alpha) by thin layer chromatography and gas chromatography-mass spectrometry. The initial reaction rate began to level off after less than 1 min of incubation at 37 degrees C. When radiolabeled 6-keto-PGF1alpha, the stable hydrolysis product of PGI2, was used as substrate under the same conditions, 97% was recovered unmetabolized after 2 min of incubation. Catabolism of PGI2 may be a major determinant of its levels in blood vessels and, therefore, may be of crucial importance to regulating the action of PGI2. Further, estimation of PGI2 generation by either tissues or organs may be misleading if only 6-keto-PGF1alpha is measured.", "contents": "Metabolism of prostacyclin in blood vessels. The activity of 15-hydroxyprostaglandin dehydrogenase has been shown to be high in both mesenteric arteries and veins; the present study suggests that it may be responsible for the inactivation of prostacyclin (PGI2). The cytoplasmic fractions of bovine mesenteric arteries and veins were incubated with radiolabeled PGI2 in the presence of NAD+ or NADP+. The substrate was rapidly converted to a product, which was isolated and identified as 6,15-diketo prostaglandin F1alpha, (6,15-diketo-PGF1alpha) by thin layer chromatography and gas chromatography-mass spectrometry. The initial reaction rate began to level off after less than 1 min of incubation at 37 degrees C. When radiolabeled 6-keto-PGF1alpha, the stable hydrolysis product of PGI2, was used as substrate under the same conditions, 97% was recovered unmetabolized after 2 min of incubation. Catabolism of PGI2 may be a major determinant of its levels in blood vessels and, therefore, may be of crucial importance to regulating the action of PGI2. Further, estimation of PGI2 generation by either tissues or organs may be misleading if only 6-keto-PGF1alpha is measured."}
{"id": "PMID:27518", "title": "Effects of pH and temperature on the interaction of an impermeant probe with surface proteins of the human red blood cell.", "content": "The conformation of the outer surface of the human red cell membrane has been studied under various conditions using the impermeant probe [125I]diazodiiodosulfanilic acid. At least seven polypeptides were labeled by the reagent, including the three extractable glycoproteins separable by the electrophoretic method employed. The Mr = 43,000 protein band was shown to contain two labeled species, one a glycoprotein, in addition to its major constituent, red cell actin. The extent and pattern of labeling were very sensitive to changes in pH and temperature. Total labeling increased with increasing pH and was greater at 4 degrees C than 37 degrees C. Binding of the probe to the Mr = 90,000 polypeptide and the major glycoprotein were relatively increased with increasing pH and temperature while opposite effects were observed for the Mr = 43,000 peptide(s). The pH effects on external membrane labeling were rapidly reversible. Results were similar in cells of different densities, suggesting that the pH and temperature effects were not related to cell age. The data presented emphasize the lability of membrane conformation and reactivity and thus the necessity to consider carefully the conditions of labeling in interpretation of studies using impermeant probes.", "contents": "Effects of pH and temperature on the interaction of an impermeant probe with surface proteins of the human red blood cell. The conformation of the outer surface of the human red cell membrane has been studied under various conditions using the impermeant probe [125I]diazodiiodosulfanilic acid. At least seven polypeptides were labeled by the reagent, including the three extractable glycoproteins separable by the electrophoretic method employed. The Mr = 43,000 protein band was shown to contain two labeled species, one a glycoprotein, in addition to its major constituent, red cell actin. The extent and pattern of labeling were very sensitive to changes in pH and temperature. Total labeling increased with increasing pH and was greater at 4 degrees C than 37 degrees C. Binding of the probe to the Mr = 90,000 polypeptide and the major glycoprotein were relatively increased with increasing pH and temperature while opposite effects were observed for the Mr = 43,000 peptide(s). The pH effects on external membrane labeling were rapidly reversible. Results were similar in cells of different densities, suggesting that the pH and temperature effects were not related to cell age. The data presented emphasize the lability of membrane conformation and reactivity and thus the necessity to consider carefully the conditions of labeling in interpretation of studies using impermeant probes."}
{"id": "PMID:27519", "title": "Solvent effects on the structure of rabbit Clq, a subcomponent of the first component of complement.", "content": "The effect of solvent conditions on the conformation of rabbit Clq was studied by both spectroscopic and nonspectroscopic methods. The conformation of Clq in buffered saline solutions at pH 7.4 or 6.0 did not differ significantly from Clq at twice the saline concentration as determined with circular dichroism, difference spectroscopy, and tritium-hydrogen exchange techniques. Addition of calcium to the buffers had no structural effects in any of the conditions examined. Hydrogen exchange experiments performed at pH 7.4 were also unaffected by magnesium, manganese, or ethylenediaminetetraacetic acid. With all the methods used a pH effect was observable between 5.1 and 8.3. From solvent perturbation difference spectroscopy results it was calculated that the equivalent of 10 +/- 2 and 6 +/- 1 mol of tyrosine and tryptophan/mol of Clq, respectively, became exposed at the lower pH. A small positive CD band in the 231 to 235 nm region decreased in wavelength and increased in magnitude as a function of decreasing pH, indicating tyrosine exposure at the lower pH and possibly changes in the collagen-like structure of Clq. Hydrogen exchange experiments indicate a small, but significant, conformation transition occurring in the pH 5 region and a stabilization of conformation between pH 6 to 8. From these results the conformational pH dependence was interpreted as an acid expansion of Clq with a minor conformational transition occurring between pH 5 AND 6. These effects may in part be associated with decreased Clq-Ig interactions which have been observed at the lower pH.", "contents": "Solvent effects on the structure of rabbit Clq, a subcomponent of the first component of complement. The effect of solvent conditions on the conformation of rabbit Clq was studied by both spectroscopic and nonspectroscopic methods. The conformation of Clq in buffered saline solutions at pH 7.4 or 6.0 did not differ significantly from Clq at twice the saline concentration as determined with circular dichroism, difference spectroscopy, and tritium-hydrogen exchange techniques. Addition of calcium to the buffers had no structural effects in any of the conditions examined. Hydrogen exchange experiments performed at pH 7.4 were also unaffected by magnesium, manganese, or ethylenediaminetetraacetic acid. With all the methods used a pH effect was observable between 5.1 and 8.3. From solvent perturbation difference spectroscopy results it was calculated that the equivalent of 10 +/- 2 and 6 +/- 1 mol of tyrosine and tryptophan/mol of Clq, respectively, became exposed at the lower pH. A small positive CD band in the 231 to 235 nm region decreased in wavelength and increased in magnitude as a function of decreasing pH, indicating tyrosine exposure at the lower pH and possibly changes in the collagen-like structure of Clq. Hydrogen exchange experiments indicate a small, but significant, conformation transition occurring in the pH 5 region and a stabilization of conformation between pH 6 to 8. From these results the conformational pH dependence was interpreted as an acid expansion of Clq with a minor conformational transition occurring between pH 5 AND 6. These effects may in part be associated with decreased Clq-Ig interactions which have been observed at the lower pH."}
{"id": "PMID:27520", "title": "Leghemoglobin. Low temperature optical spectra of acid and alkaline forms of leghemoglobin(IV). Configuration of the heme.", "content": "Leghemoglobin(IV), the derivative of leghemoglobin at the formal oxidation state IV, when cooled to liquid nitrogen temperature exhibits radically different spectra at acid and alkaline pH. The acid and alkaline forms are freely interconvertible. The optical spectrum of the acid form is closely similar to optical spectra of the red higher oxidation states of horseradish and cytochrome c peroxidases, showing that the configuration of the heme iron is the same throughout this family of compounds. That configuration is believed to be Fe(IV) in a porphyrin environment. The optical spectrum of the alkaline form of leghemoglobin(IV) recalls that of alkaline low spin ferric leghemoglobin. Near infrared spectra of leghemoglobin(IV), myoglobin(IV), and the higher oxidation states of the peroxidases are featureless to 1300 nm, suggesting a common structural feature. The acid form of leghemoglobin(IV), seen in fluid buffer as a transient species at pH 5 or less, is conveniently generated by cooling a solution of the more stable alkaline form in borate buffer to liquid nitrogen temperature. At this temperature borate buffers become acid.", "contents": "Leghemoglobin. Low temperature optical spectra of acid and alkaline forms of leghemoglobin(IV). Configuration of the heme. Leghemoglobin(IV), the derivative of leghemoglobin at the formal oxidation state IV, when cooled to liquid nitrogen temperature exhibits radically different spectra at acid and alkaline pH. The acid and alkaline forms are freely interconvertible. The optical spectrum of the acid form is closely similar to optical spectra of the red higher oxidation states of horseradish and cytochrome c peroxidases, showing that the configuration of the heme iron is the same throughout this family of compounds. That configuration is believed to be Fe(IV) in a porphyrin environment. The optical spectrum of the alkaline form of leghemoglobin(IV) recalls that of alkaline low spin ferric leghemoglobin. Near infrared spectra of leghemoglobin(IV), myoglobin(IV), and the higher oxidation states of the peroxidases are featureless to 1300 nm, suggesting a common structural feature. The acid form of leghemoglobin(IV), seen in fluid buffer as a transient species at pH 5 or less, is conveniently generated by cooling a solution of the more stable alkaline form in borate buffer to liquid nitrogen temperature. At this temperature borate buffers become acid."}
{"id": "PMID:27521", "title": "Acid and alkaline forms of the higher oxidation state of kangaroo, horse, and sperm whale myoglobin.", "content": "Myoglobin(IV), the derivative of myoglobin at the formal oxidation state IV, prepared from kangaroo (Megaleia rufa), horse, or sperm whale myoglobin, when cooled to liquid nitrogen temperature, assumes acid and alkaline forms with different optical spectra. The essential features of the optical spectra of the acid forms are the same as those of leghemoglobin(IV) and are very similar to those of optical spectra of the red higher oxidation states of catalases and peroxidases. This shows that the configuration of the heme iron is the same throughout these compounds. That configuration is believed to be Fe(IV) in a porphyrin environment. The optical spectra of alkaline mammalian myoglobin(IV), like that of alkaline leghemoglobin(IV), resemble those of the alkaline low spin ferric proteins. Kangaroo myoglobin(IV) may be prepared by reaction of ferrous myoglobin with hydrogen peroxide. The acid forms of myoglobin(IV) are conveniently prepared by cooling solutions in borate buffers, initially pH 8.3, to liquid nitrogen temperature. At this temperature borate buffers become acidic.", "contents": "Acid and alkaline forms of the higher oxidation state of kangaroo, horse, and sperm whale myoglobin. Myoglobin(IV), the derivative of myoglobin at the formal oxidation state IV, prepared from kangaroo (Megaleia rufa), horse, or sperm whale myoglobin, when cooled to liquid nitrogen temperature, assumes acid and alkaline forms with different optical spectra. The essential features of the optical spectra of the acid forms are the same as those of leghemoglobin(IV) and are very similar to those of optical spectra of the red higher oxidation states of catalases and peroxidases. This shows that the configuration of the heme iron is the same throughout these compounds. That configuration is believed to be Fe(IV) in a porphyrin environment. The optical spectra of alkaline mammalian myoglobin(IV), like that of alkaline leghemoglobin(IV), resemble those of the alkaline low spin ferric proteins. Kangaroo myoglobin(IV) may be prepared by reaction of ferrous myoglobin with hydrogen peroxide. The acid forms of myoglobin(IV) are conveniently prepared by cooling solutions in borate buffers, initially pH 8.3, to liquid nitrogen temperature. At this temperature borate buffers become acidic."}
{"id": "PMID:27523", "title": "Molecular properties of a major cell surface protein from chick embryo fibroblasts.", "content": "The molecular structure of chick embryo fibroblast cell surface protein has been investigated by ultracentrifugation, circular dichroism, and fluorescence. Most measurements were restricted to alkaline solutions because of the limited solubility of this protein at more neutral pH values. A very high frictional ratio for the protein suggests an asymmetric structure. However, there are elements of organized structure since typical thermal transition curves were found by several methods. Consequently, a model in which ordered domains are connected by flexible polypeptide chains seems to account for all the hydrodynamic and optical data.", "contents": "Molecular properties of a major cell surface protein from chick embryo fibroblasts. The molecular structure of chick embryo fibroblast cell surface protein has been investigated by ultracentrifugation, circular dichroism, and fluorescence. Most measurements were restricted to alkaline solutions because of the limited solubility of this protein at more neutral pH values. A very high frictional ratio for the protein suggests an asymmetric structure. However, there are elements of organized structure since typical thermal transition curves were found by several methods. Consequently, a model in which ordered domains are connected by flexible polypeptide chains seems to account for all the hydrodynamic and optical data."}
{"id": "PMID:27524", "title": "Rupture of the plantar fascia in athletes.", "content": "Symptoms resembling those of plantar fasciitis were seen in six athletes who were thought to have a partial rupture of the plantar fascia. Treatment, which included the use of crutches, anti-inflammatory agents, strapping of the arch, and ice packs, was successful in all but one patient who had a painful mass in the area of the previous rupture. After surgical excision of the painful mass and release of the fascia, he recovered. Five of the six athletes had been previously treated with repeated local injections of steroid.", "contents": "Rupture of the plantar fascia in athletes. Symptoms resembling those of plantar fasciitis were seen in six athletes who were thought to have a partial rupture of the plantar fascia. Treatment, which included the use of crutches, anti-inflammatory agents, strapping of the arch, and ice packs, was successful in all but one patient who had a painful mass in the area of the previous rupture. After surgical excision of the painful mass and release of the fascia, he recovered. Five of the six athletes had been previously treated with repeated local injections of steroid."}
{"id": "PMID:27525", "title": "Glucocorticoid induction of tyrosine hydroxylase in a continous cell line of rat pheochromocytoma.", "content": "We have established a continous cell line (G1) in which the tyrosine hydroxylase specific activity is increased as much as 50-100-fold in response to dexamethasone. This response is specific for the glucocorticoid class of steroid hormones; it is elicited by dexamethasone, corticosterone, and triamcinolone, but not by estradiol, testosterone, progesterone, or deoxycorticosterone acetate. The increase in tyrosine hydroxylase specific activity is likely to be due to the increased synthesis of new enzyme protein rather than an activation of existing protein molecules, inasmuch as this increase is completely blocked by cycloheximide.", "contents": "Glucocorticoid induction of tyrosine hydroxylase in a continous cell line of rat pheochromocytoma. We have established a continous cell line (G1) in which the tyrosine hydroxylase specific activity is increased as much as 50-100-fold in response to dexamethasone. This response is specific for the glucocorticoid class of steroid hormones; it is elicited by dexamethasone, corticosterone, and triamcinolone, but not by estradiol, testosterone, progesterone, or deoxycorticosterone acetate. The increase in tyrosine hydroxylase specific activity is likely to be due to the increased synthesis of new enzyme protein rather than an activation of existing protein molecules, inasmuch as this increase is completely blocked by cycloheximide."}
{"id": "PMID:27526", "title": "Inhibition of glucose transport in human erythrocytes by benzylalcohol.", "content": "The inhibition of glucose transport by the non-ionizable local-anesthetic denzylalcohol is of the mixed type and independent of pH. The affinity of benzylalcohol to the free carrier is about three times larger than that to the carrier-glucose complex.", "contents": "Inhibition of glucose transport in human erythrocytes by benzylalcohol. The inhibition of glucose transport by the non-ionizable local-anesthetic denzylalcohol is of the mixed type and independent of pH. The affinity of benzylalcohol to the free carrier is about three times larger than that to the carrier-glucose complex."}
{"id": "PMID:27527", "title": "Culture pH, CO2 tension, and cell division in Euglena gracilis Z.", "content": "Growth characteristics of Euglena gracilis Z as functions of culture pH, CO2 tension, temperature, and lighting regime were investigated. The results are consistent with the possibility that cell division is preceded by a lowered intracellular pH. Also consistent with this possibility is the finding that division rhythmicity can be induced by periodic changes in CO2 tension. It is suggested that the rhythmicity is induced by changes in intracellular pH produced by carbonic acid.", "contents": "Culture pH, CO2 tension, and cell division in Euglena gracilis Z. Growth characteristics of Euglena gracilis Z as functions of culture pH, CO2 tension, temperature, and lighting regime were investigated. The results are consistent with the possibility that cell division is preceded by a lowered intracellular pH. Also consistent with this possibility is the finding that division rhythmicity can be induced by periodic changes in CO2 tension. It is suggested that the rhythmicity is induced by changes in intracellular pH produced by carbonic acid."}
{"id": "PMID:27528", "title": "Effects of acidified fetal bovine serum on the fibrinolytic activity and growth of cells in culture.", "content": "The fibrinolytic activity of cells in culture varied with the type of serum employed in the growth medium. Degradation of iodinated fibrin occurred slowly when Rous sarcoma virus-transformed chick embryo fibroblasts were grown in medium containing fetal bovine serum (FBS), and rapidly when chicken serum was employed. This difference reflected the low plasminogen and high inhibitor content of FBS. The inhibitors were found to be serum macromolecules that were precipitated with ammonium sulfate or polyethylene glycol, and were inactivated by boiling or upon exposure to acidic conditions. No inhibitor activity was detected in fetuin, one of the major proteins present in FBS. Acidified FBS was similar to chicken serum in that both supported high rates of cell-mediated fibrinolytic activity. Although virally transformed hamster, mouse and chicken cells grew well in acid-treated FBS, their normal counterparts did not. Apparently, acifification resulted in the formation of materials that were toxic to normal cells. These agents rapidly blocked cellular DNA synthesis.", "contents": "Effects of acidified fetal bovine serum on the fibrinolytic activity and growth of cells in culture. The fibrinolytic activity of cells in culture varied with the type of serum employed in the growth medium. Degradation of iodinated fibrin occurred slowly when Rous sarcoma virus-transformed chick embryo fibroblasts were grown in medium containing fetal bovine serum (FBS), and rapidly when chicken serum was employed. This difference reflected the low plasminogen and high inhibitor content of FBS. The inhibitors were found to be serum macromolecules that were precipitated with ammonium sulfate or polyethylene glycol, and were inactivated by boiling or upon exposure to acidic conditions. No inhibitor activity was detected in fetuin, one of the major proteins present in FBS. Acidified FBS was similar to chicken serum in that both supported high rates of cell-mediated fibrinolytic activity. Although virally transformed hamster, mouse and chicken cells grew well in acid-treated FBS, their normal counterparts did not. Apparently, acifification resulted in the formation of materials that were toxic to normal cells. These agents rapidly blocked cellular DNA synthesis."}
{"id": "PMID:27530", "title": "Effects of methylprednisolone on hydrogen ion absorption in the canine stomach.", "content": "The effect of methylprednisolone (2 mg/kg per day given parenterally for 3 doses, 2 wk or 12 wk) on the permeability of mammalian gastric mucosa to hydrogen ion (H(+)) was examined with denervated fundic pouches in dogs with antrectomies. Transmucosal electric potential difference (PD) and net fluxes of H(+) and Na(+) were determined for luminal [H(+)] from 20 to 160 mM and [Na(+)] from 1 to 140 mM ([H(+)] and [Na(+)] were varied reciprocally). The PD was 50-60 mV lumen negative and was constant over the entire range of Na(+) and H(+) concentration tested. Net H(+) flux varied linearly with [H(+)]. Extrapolation indicated apparent H(+) loss at zero luminal concentration, suggesting a basal HCO(3) (-) secretion. Addition of acetylsalicylic acid (ASA) or taurocholate decreased the PD to 30-40 mV and increased threefold the slope of the relation between net H(+) flux and [H(+)] (k(H)). Calculation of PD-independent permeability constants for H(+) (P(H)) with the Goldman constant field equation indicated that this increase in k(H) could not be attributed solely to the associated decrease in PD. Prednisolone administered for 3 doses had no effect on either the basal mucosal permeability to H(+) or the altered permeability induced by ASA or taurocholate. Chronic administration induced a low rate of basal acid secretion (at 12 wk) but had no effect on either PD or k(H). However, the increase in k(H) and P(H) that developed upon addition of ASA or taurocholate in chronically treated dogs was more than one and a half times that of controls. These data suggest that prolonged treatment with glucocorticoids increases susceptibility of the gastric mucosa to damage by agents that increase permeability to H(+).", "contents": "Effects of methylprednisolone on hydrogen ion absorption in the canine stomach. The effect of methylprednisolone (2 mg/kg per day given parenterally for 3 doses, 2 wk or 12 wk) on the permeability of mammalian gastric mucosa to hydrogen ion (H(+)) was examined with denervated fundic pouches in dogs with antrectomies. Transmucosal electric potential difference (PD) and net fluxes of H(+) and Na(+) were determined for luminal [H(+)] from 20 to 160 mM and [Na(+)] from 1 to 140 mM ([H(+)] and [Na(+)] were varied reciprocally). The PD was 50-60 mV lumen negative and was constant over the entire range of Na(+) and H(+) concentration tested. Net H(+) flux varied linearly with [H(+)]. Extrapolation indicated apparent H(+) loss at zero luminal concentration, suggesting a basal HCO(3) (-) secretion. Addition of acetylsalicylic acid (ASA) or taurocholate decreased the PD to 30-40 mV and increased threefold the slope of the relation between net H(+) flux and [H(+)] (k(H)). Calculation of PD-independent permeability constants for H(+) (P(H)) with the Goldman constant field equation indicated that this increase in k(H) could not be attributed solely to the associated decrease in PD. Prednisolone administered for 3 doses had no effect on either the basal mucosal permeability to H(+) or the altered permeability induced by ASA or taurocholate. Chronic administration induced a low rate of basal acid secretion (at 12 wk) but had no effect on either PD or k(H). However, the increase in k(H) and P(H) that developed upon addition of ASA or taurocholate in chronically treated dogs was more than one and a half times that of controls. These data suggest that prolonged treatment with glucocorticoids increases susceptibility of the gastric mucosa to damage by agents that increase permeability to H(+)."}
{"id": "PMID:27531", "title": "The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism.", "content": "Previous studies in vivo and with isolated perfused rat livers have suggested that the deleterious effect of ethanol on hepatic pyridoxal 5'-phosphate metabolism is mediated by acetaldehyde. Inasmuch as acetaldehyde has no effect on the synthesis of pyridoxal phosphate, it has also been postulated that acetaldehyde accelerates pyridoxal phosphate degradation by displacing this coenzyme from binding proteins, which protect it against hydrolysis. To test these hypotheses, studies have been performed with isolated rat hepatocytes, subcellular fractions of rat liver, and human erythrocytes. Ethanol oxidation lowered the pyridoxal phosphate content of isolated liver cells when acetaldehyde oxidation was inhibited by either disulfiram or prior treatment of rats with cyanamide. Additions of 7.5 mM acetaldehyde alone at 40-min intervals to cell suspensions decreased hepatic pyridoxal phosphate content only slightly because acetaldehyde was rapidly metabolized. However, when acetaldehyde oxidation and reduction were inhibited by cyanamide treatment and by 4-methyl-pyrazole and isobutyramide, respectively, a 40% decrease in hepatic pyridoxal phosphate content was observed in 80 min of incubation. In equilibrium dialysis experiments, acetaldehyde, 7.5 and 15 mM, displaced protein-bound pyridoxal phosphate in undialyzed hepatic cytosol and in hemolysate supernate containing added pyridoxal phosphate. In the presence of alkaline phosphatase, acetaldehyde accelerated the degradation of pyridoxal phosphate in dialyzed hemolysate supernate and hepatic cytosol with added pyridoxal phosphate. Acetaldehyde also inhibits tyrosine aminotransferase. The kinetics of inhibition were mixed competitive-noncompetitive with respect to pyridoxal phosphate. These observations support the hypothesis that the deleterious effect of ethanol oxidation on pyridoxal phosphate metabolism is mediated at least in part by acetaldehyde which displaces this coenzyme from protein binding, thereby enhancing its degradation.", "contents": "The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism. Previous studies in vivo and with isolated perfused rat livers have suggested that the deleterious effect of ethanol on hepatic pyridoxal 5'-phosphate metabolism is mediated by acetaldehyde. Inasmuch as acetaldehyde has no effect on the synthesis of pyridoxal phosphate, it has also been postulated that acetaldehyde accelerates pyridoxal phosphate degradation by displacing this coenzyme from binding proteins, which protect it against hydrolysis. To test these hypotheses, studies have been performed with isolated rat hepatocytes, subcellular fractions of rat liver, and human erythrocytes. Ethanol oxidation lowered the pyridoxal phosphate content of isolated liver cells when acetaldehyde oxidation was inhibited by either disulfiram or prior treatment of rats with cyanamide. Additions of 7.5 mM acetaldehyde alone at 40-min intervals to cell suspensions decreased hepatic pyridoxal phosphate content only slightly because acetaldehyde was rapidly metabolized. However, when acetaldehyde oxidation and reduction were inhibited by cyanamide treatment and by 4-methyl-pyrazole and isobutyramide, respectively, a 40% decrease in hepatic pyridoxal phosphate content was observed in 80 min of incubation. In equilibrium dialysis experiments, acetaldehyde, 7.5 and 15 mM, displaced protein-bound pyridoxal phosphate in undialyzed hepatic cytosol and in hemolysate supernate containing added pyridoxal phosphate. In the presence of alkaline phosphatase, acetaldehyde accelerated the degradation of pyridoxal phosphate in dialyzed hemolysate supernate and hepatic cytosol with added pyridoxal phosphate. Acetaldehyde also inhibits tyrosine aminotransferase. The kinetics of inhibition were mixed competitive-noncompetitive with respect to pyridoxal phosphate. These observations support the hypothesis that the deleterious effect of ethanol oxidation on pyridoxal phosphate metabolism is mediated at least in part by acetaldehyde which displaces this coenzyme from protein binding, thereby enhancing its degradation."}
{"id": "PMID:27532", "title": "Human erythrocyte hexokinase deficiency. Characterization of a mutant enzyme with abnormal regulatory properties.", "content": "In the erythrocytes of a patient with hereditary nonspherocytic hemolytic anemia, a homozygous expression of hexokinase deficiency was detected. The mutant enzyme was characterized by normal kinetic parameters with respect to its substrates, glucose and MgATP2-, normal pH optimum, normal heat stability at 40 degrees C, but abnormal behavior with respect to its regulation by glucose-1,6-diphosphate and inorganic phosphate, and an altered electrophoretic pattern. Interpretation of the results revealed the presence of two different hexokinases type I in normal human erythrocytes: one enzyme with a high affinity for glucose-1,6-diphosphate, the inhibition of which is regulated by inorganic phosphate; and another enzyme with a lower affinity for the inhibitor, not regulated by inorganic phosphate. The former enzyme was not detectable in the erythrocytes of the patient, whereas the presence of the latter enzyme could be demonstrated.", "contents": "Human erythrocyte hexokinase deficiency. Characterization of a mutant enzyme with abnormal regulatory properties. In the erythrocytes of a patient with hereditary nonspherocytic hemolytic anemia, a homozygous expression of hexokinase deficiency was detected. The mutant enzyme was characterized by normal kinetic parameters with respect to its substrates, glucose and MgATP2-, normal pH optimum, normal heat stability at 40 degrees C, but abnormal behavior with respect to its regulation by glucose-1,6-diphosphate and inorganic phosphate, and an altered electrophoretic pattern. Interpretation of the results revealed the presence of two different hexokinases type I in normal human erythrocytes: one enzyme with a high affinity for glucose-1,6-diphosphate, the inhibition of which is regulated by inorganic phosphate; and another enzyme with a lower affinity for the inhibitor, not regulated by inorganic phosphate. The former enzyme was not detectable in the erythrocytes of the patient, whereas the presence of the latter enzyme could be demonstrated."}
{"id": "PMID:27533", "title": "Passive transfer by cells of type II collagen-induced arthritis in rats.", "content": "To investigate the role of immunologic hypersensitivity to collagen in the causation of type II collagen-induced arthritis in rats, passive transfer experiments were performed. Wistar/Lewis rats used in these experiments were demonstrated to be histocompatible by prolonged skin graft survival and mixed lymphocyte cultures. Popliteal lymph node weight assays excluded a potential for graft-vs.-host reactivity in this strain. 9 of 32 naive rats developed arthritis after intravenous receipt of pooled spleen and lymph node cells from donors that had been injected intradermally with type II collagen emulsified in incomplete Freund's adjuvant. This passively transferred synovitis was evident clinically as well as histologically. In control cell transfer experiments involving a total of 97 recipients, transfer of arthritis was shown to require viable cells sensitized to type II collagen. These controls included 17 rats receiving cells from unimmunized donors, 20 recipients of cells from donors injected with incomplete Freund's adjuvant alone, and 24 recipients of cells from rats injected with type I collagen in adjuvant. Deliberate addition of solubilized type II collagen to unsensitized cells at the time of transfer or injection of heat-killed sensitized cells also did not cause arthritis in a total of 36 recipients. These latter two control groups indicate that disease transfer was not the result of antigen carry-over. Intravenous injection of sera from arthritic donors was incapable of passively transferring clinical or histologic synovitis in 30 recipients. Thus, these studies directly implicate immunologic sensitivity to the cartilage type of collagen in the etiology of this autoimmune disease.", "contents": "Passive transfer by cells of type II collagen-induced arthritis in rats. To investigate the role of immunologic hypersensitivity to collagen in the causation of type II collagen-induced arthritis in rats, passive transfer experiments were performed. Wistar/Lewis rats used in these experiments were demonstrated to be histocompatible by prolonged skin graft survival and mixed lymphocyte cultures. Popliteal lymph node weight assays excluded a potential for graft-vs.-host reactivity in this strain. 9 of 32 naive rats developed arthritis after intravenous receipt of pooled spleen and lymph node cells from donors that had been injected intradermally with type II collagen emulsified in incomplete Freund's adjuvant. This passively transferred synovitis was evident clinically as well as histologically. In control cell transfer experiments involving a total of 97 recipients, transfer of arthritis was shown to require viable cells sensitized to type II collagen. These controls included 17 rats receiving cells from unimmunized donors, 20 recipients of cells from donors injected with incomplete Freund's adjuvant alone, and 24 recipients of cells from rats injected with type I collagen in adjuvant. Deliberate addition of solubilized type II collagen to unsensitized cells at the time of transfer or injection of heat-killed sensitized cells also did not cause arthritis in a total of 36 recipients. These latter two control groups indicate that disease transfer was not the result of antigen carry-over. Intravenous injection of sera from arthritic donors was incapable of passively transferring clinical or histologic synovitis in 30 recipients. Thus, these studies directly implicate immunologic sensitivity to the cartilage type of collagen in the etiology of this autoimmune disease."}
{"id": "PMID:27534", "title": "The effect of complement depletion on lung clearance of bacteria.", "content": "We have investigated the effect of hypocomplementemia on early pulmonary clearance of four species of bacteria. The experiments were performed in an inbred animal model to minimize immunologic variability. Complement was depleted by cobra venom factor, and activity in serum was monitored with a phagocytic assay. Bacterial specific antibodies were examined by an indirect radioimmunoassay, and animals with high levels of activity were excluded from anaysis. 4 h after aerosolization with Streptococcus pneumoniae, complement-depleted animals had cleared only 75% of the initial number of organisms, whereas saline-treated controls cleared 91% (P less than 0.01). Aerosolization with Pseudomonas aeruginosa was followed at 4 h by a twofold greater growth of organisms in the complement-depleted animals (446% of original deposition) as compared to the saline-treated controls (211% of original deposition) (P less than 0.02). Clearance of Klebsiella pneumoniae and Staphylococcus aureus were similar in complement-depleted animals and saline-treated controls. These experiments suggest that hypocomplementemia predisposes to bacterial pneumonia and may explain the high incidence of pulmonary infections in patients having impaired complement activity. Our results further indicate that varying defense mechanisms may be involved with clearing the lung of differing bacterial species.", "contents": "The effect of complement depletion on lung clearance of bacteria. We have investigated the effect of hypocomplementemia on early pulmonary clearance of four species of bacteria. The experiments were performed in an inbred animal model to minimize immunologic variability. Complement was depleted by cobra venom factor, and activity in serum was monitored with a phagocytic assay. Bacterial specific antibodies were examined by an indirect radioimmunoassay, and animals with high levels of activity were excluded from anaysis. 4 h after aerosolization with Streptococcus pneumoniae, complement-depleted animals had cleared only 75% of the initial number of organisms, whereas saline-treated controls cleared 91% (P less than 0.01). Aerosolization with Pseudomonas aeruginosa was followed at 4 h by a twofold greater growth of organisms in the complement-depleted animals (446% of original deposition) as compared to the saline-treated controls (211% of original deposition) (P less than 0.02). Clearance of Klebsiella pneumoniae and Staphylococcus aureus were similar in complement-depleted animals and saline-treated controls. These experiments suggest that hypocomplementemia predisposes to bacterial pneumonia and may explain the high incidence of pulmonary infections in patients having impaired complement activity. Our results further indicate that varying defense mechanisms may be involved with clearing the lung of differing bacterial species."}
{"id": "PMID:27535", "title": "Effects of alpha adrenergic blockade upon coronary hemodynamics.", "content": "The effect of alpha adrenergic block-ade on coronary blood flow regulation at rest was studied in 11 normally innervated patients and 8 cardiac allograft recipients by measuring arterial pressure and coronary sinus blood flow by thermodilution before and after alpha adrenergic blockade with phentolamine. Coronary vascular resistance was calculated by using coronary sinus blood flow and mean arterial pressure, and metabolic demand was estimated by the product of systolic arterial pressure and heart rate. In addition, the coronary sinus blood flow response to tachycardia was examined in 9 innervated patients and 12 denervated patients, with measurements repeated after phentolamine in 8 of the 9 innvervated patients and 6 of the 12 denervated patients. There was a 7.3+/-4.4% increase in coronary sinus blood flow in the innervated patients in response to alpha blockade, whereas the transplanted patients had an 8.2+/-1.8% fall in coronary sinus blood flow, despite equivalent changes in rate pressure product. The innervated patients also demonstrated a significantly greater increase in coronary sinus blood flow than did the transplanted patients during the first 5 s of an abrupt increase in heart rate (26+/-4 vs. 8+/-2.5 ml/min, P <0.001). This early response was blunted after alpha adrenergic blockade. We conclude that there is basal alpha adrenergic tone present on the coronary vasculature in man that is withdrawn by a sudden increase in heart rate.", "contents": "Effects of alpha adrenergic blockade upon coronary hemodynamics. The effect of alpha adrenergic block-ade on coronary blood flow regulation at rest was studied in 11 normally innervated patients and 8 cardiac allograft recipients by measuring arterial pressure and coronary sinus blood flow by thermodilution before and after alpha adrenergic blockade with phentolamine. Coronary vascular resistance was calculated by using coronary sinus blood flow and mean arterial pressure, and metabolic demand was estimated by the product of systolic arterial pressure and heart rate. In addition, the coronary sinus blood flow response to tachycardia was examined in 9 innervated patients and 12 denervated patients, with measurements repeated after phentolamine in 8 of the 9 innvervated patients and 6 of the 12 denervated patients. There was a 7.3+/-4.4% increase in coronary sinus blood flow in the innervated patients in response to alpha blockade, whereas the transplanted patients had an 8.2+/-1.8% fall in coronary sinus blood flow, despite equivalent changes in rate pressure product. The innervated patients also demonstrated a significantly greater increase in coronary sinus blood flow than did the transplanted patients during the first 5 s of an abrupt increase in heart rate (26+/-4 vs. 8+/-2.5 ml/min, P <0.001). This early response was blunted after alpha adrenergic blockade. We conclude that there is basal alpha adrenergic tone present on the coronary vasculature in man that is withdrawn by a sudden increase in heart rate."}
{"id": "PMID:27536", "title": "gamma-Glutamyl transferase isoenzymes in human bile.", "content": "The gamma-glutamyl transferase isoenzymes of bile were studied using electrophoretic, gel filtration, and ultracentrifugation techniques. In view of the known association of other biliary enzymes with lipids the effects of butanol extraction were investigated. The results show the presence of four isoenzymes of gamma-glutamyl transferase in bile, differing in electrophoretic mobilities, molecular size, and density. The correlation between the properties of biliary gamma-glutamyl transferase and of alkaline phosphatase is discussed.", "contents": "gamma-Glutamyl transferase isoenzymes in human bile. The gamma-glutamyl transferase isoenzymes of bile were studied using electrophoretic, gel filtration, and ultracentrifugation techniques. In view of the known association of other biliary enzymes with lipids the effects of butanol extraction were investigated. The results show the presence of four isoenzymes of gamma-glutamyl transferase in bile, differing in electrophoretic mobilities, molecular size, and density. The correlation between the properties of biliary gamma-glutamyl transferase and of alkaline phosphatase is discussed."}
{"id": "PMID:27537", "title": "Plasma levels of clobazam after three oral dosage forms in health subjects.", "content": "As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement.", "contents": "Plasma levels of clobazam after three oral dosage forms in health subjects. As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement."}
{"id": "PMID:27539", "title": "Clobazam versus diazepam--a double-blind study in anxiety neurosis.", "content": "Clobazam, a new antianxiety compound, was compared in a double-blind study  with diazepam in 40 neurotic outpatients. Twenty-three patients completed the trial under clobazam conditions while 17 patients completed the trial under diazepam conditions. The trial was conducted for a period of four weeks of active drug administration followed by a one-week period of placebo administration. Clobazam was administered in three divided doses of 30 to 40 mg/day, while diazepam was administered in three divided doses of 15 to 20 mg/day, following a fixed dosage schedule. No significant differences were noted between the two treatment conditions during the drug trial period. The patients on clobazam maintained greater improvement during the placebo trial period for the variables \"somatic anxiety\" and \"nights of sleep disturbance.\" Simultaneous motor coordination tests (hand steadiness test) showed greater improvement on clobazam throughout the trial period in patients with an initial error score greater than 50 points. This difference was significant during the second week of the trial.", "contents": "Clobazam versus diazepam--a double-blind study in anxiety neurosis. Clobazam, a new antianxiety compound, was compared in a double-blind study  with diazepam in 40 neurotic outpatients. Twenty-three patients completed the trial under clobazam conditions while 17 patients completed the trial under diazepam conditions. The trial was conducted for a period of four weeks of active drug administration followed by a one-week period of placebo administration. Clobazam was administered in three divided doses of 30 to 40 mg/day, while diazepam was administered in three divided doses of 15 to 20 mg/day, following a fixed dosage schedule. No significant differences were noted between the two treatment conditions during the drug trial period. The patients on clobazam maintained greater improvement during the placebo trial period for the variables \"somatic anxiety\" and \"nights of sleep disturbance.\" Simultaneous motor coordination tests (hand steadiness test) showed greater improvement on clobazam throughout the trial period in patients with an initial error score greater than 50 points. This difference was significant during the second week of the trial."}
{"id": "PMID:27542", "title": "Lactostrepcins--acid bacteriocins produced by lactic streptococci.", "content": "All 47 non-nisin producing strains of Streptococcus lactis and 12/13 strains of Str. lactis subsp. diacetylactis examined produced bacteriocins, for which the term lactostrepcins is suggested. Seven strains of Str. cremoris examined produced no bacteriocins active against 3 lactic streptococci strains used as indicators. The strains examined were divided into 3 groups: I, those producing lactostrepcins active against only one streptomycin resistant mutant of Str. lactis 60 indicator strain; II, those producing lactostrepcins active against all 3 indicator strains; III, those not producing lactostrepcins active against the indicator strains employed. The lactostrepcins were sensitive to various proteolytic enzymes and to phospholipase D, but retained full or partial activity after dialysis. Most of the bacteriocins studied were fully active only within the pH range 4.2--5.0 and were reversibly inactivated at pH 7.0 or 8.0. Results suggested occurrence of 4 different lactostrepcins. The lactostrepcins produced by all group I strains were the same, but there were differences among the lactostrepcins produced by group II strains. Lactostrepcins killed some beta-haemolytic streptococci and some strains of Lactobacillus helveticus. One of the lactostrepcins was also active against certain Leuconostoc strains, but not against other Leuconostoc strains, nor against L. helveticus or other Gram-positive bacteria.", "contents": "Lactostrepcins--acid bacteriocins produced by lactic streptococci. All 47 non-nisin producing strains of Streptococcus lactis and 12/13 strains of Str. lactis subsp. diacetylactis examined produced bacteriocins, for which the term lactostrepcins is suggested. Seven strains of Str. cremoris examined produced no bacteriocins active against 3 lactic streptococci strains used as indicators. The strains examined were divided into 3 groups: I, those producing lactostrepcins active against only one streptomycin resistant mutant of Str. lactis 60 indicator strain; II, those producing lactostrepcins active against all 3 indicator strains; III, those not producing lactostrepcins active against the indicator strains employed. The lactostrepcins were sensitive to various proteolytic enzymes and to phospholipase D, but retained full or partial activity after dialysis. Most of the bacteriocins studied were fully active only within the pH range 4.2--5.0 and were reversibly inactivated at pH 7.0 or 8.0. Results suggested occurrence of 4 different lactostrepcins. The lactostrepcins produced by all group I strains were the same, but there were differences among the lactostrepcins produced by group II strains. Lactostrepcins killed some beta-haemolytic streptococci and some strains of Lactobacillus helveticus. One of the lactostrepcins was also active against certain Leuconostoc strains, but not against other Leuconostoc strains, nor against L. helveticus or other Gram-positive bacteria."}
{"id": "PMID:27544", "title": "Blood and tissue distribution of gamma glutamyl transferase in calves.", "content": "In five male and five female calves, we studied the tissue distribution of gamma-glutamyl transferase. The enzyme was mainly in kidney, pancreas, and liver; there was no sex-related difference. The relative hepatic and pancreatic specificity of the enzyme indicated that the measure of its activity in serum could be a test of hepatic or pancreatic damage in the calf. Serum activity measured within 159 samples of apparently healthy calves was 15.3 +/- 3.7 U/liter, not differing significantly from that of adult cow.", "contents": "Blood and tissue distribution of gamma glutamyl transferase in calves. In five male and five female calves, we studied the tissue distribution of gamma-glutamyl transferase. The enzyme was mainly in kidney, pancreas, and liver; there was no sex-related difference. The relative hepatic and pancreatic specificity of the enzyme indicated that the measure of its activity in serum could be a test of hepatic or pancreatic damage in the calf. Serum activity measured within 159 samples of apparently healthy calves was 15.3 +/- 3.7 U/liter, not differing significantly from that of adult cow."}
{"id": "PMID:27545", "title": "Nutrition policy--from neglect and uncertainty to debate and action.", "content": "Until recent years, nutrition has received little attention in U.S. agriculture, food, and health policies. This circumstance is changing. In the late sixties and early seventies, reports of hunger and malnutrition sparked public reaction and a shift in policy. The White House Conference on Food, Nutrition and Health in 1971 prompted the Senate select Committee on Nutrition and Human Needs to address itself to this problem, with the result that the Food Stamp, child nutrition, WIC, and Nutrition for the Elderly programs were initiated or expanded. Then, in the mid-seventies, the Select Committee turned its attention to broader issues of nutrition and health and declared that the goal of any food system is the maintenance and improvement of nutritional health of the population. This objective emerged as public policy in the Food and Agriculture Act of 1977. As the Select Committee continued its work, problems of overnutrition became more apparent. The culmination of its studies was the issuance early in 1977 of the \"Dietary Goals for the United States,\" designed to improve the nutrition and reduce health problems of the population. To that same end, the Select Committee has also made recommendations regarding food labeling and nutrition education.", "contents": "Nutrition policy--from neglect and uncertainty to debate and action. Until recent years, nutrition has received little attention in U.S. agriculture, food, and health policies. This circumstance is changing. In the late sixties and early seventies, reports of hunger and malnutrition sparked public reaction and a shift in policy. The White House Conference on Food, Nutrition and Health in 1971 prompted the Senate select Committee on Nutrition and Human Needs to address itself to this problem, with the result that the Food Stamp, child nutrition, WIC, and Nutrition for the Elderly programs were initiated or expanded. Then, in the mid-seventies, the Select Committee turned its attention to broader issues of nutrition and health and declared that the goal of any food system is the maintenance and improvement of nutritional health of the population. This objective emerged as public policy in the Food and Agriculture Act of 1977. As the Select Committee continued its work, problems of overnutrition became more apparent. The culmination of its studies was the issuance early in 1977 of the \"Dietary Goals for the United States,\" designed to improve the nutrition and reduce health problems of the population. To that same end, the Select Committee has also made recommendations regarding food labeling and nutrition education."}
{"id": "PMID:27546", "title": "Comparison of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in geriatric patients.", "content": "In a four-week study, a comparison was made of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in 17 geriatric patients. Each drug was given alone for six nights, with a two-night placebo interval following each phase. Each patient completed an additional placebo phase (up to six nights) before each drug phase. The number of awakenings per night and the sleep latency (time required to fall asleep) were determined from the patients' reports and from the reports of a nurse-observer. Only for oxazepam was the number of patient-reported awakenings per night significantly less than for placebo, although with both oxazepam and flurazepam the awakenings were fewer than with chloral hydrate. According to the patient-reports, sleep latency was significantly lower with flurazepam than with placebo; for oxazepam and chloral hydrate the latencies were not significantly different from those for flurazepam or placebo. Only for oxazepam were the patients' ratings of sleep quality significantly greater than for placebo. The objective assessment of sleep by the nurse-observer usually confirmed the patients' assessments. Morning drowsiness was the most common side effect, reported equally for placebo and for the active drugs. Drowsiness during the day was reported less frequently for oxazepam than for flurazepam, chloral hydrate or placebo. It is concluded that oxazepam is safe and efficacious for the short-term management of insomnia in the elderly.", "contents": "Comparison of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in geriatric patients. In a four-week study, a comparison was made of oxazepam, flurazepam and chloral hydrate as hypnotic sedatives in 17 geriatric patients. Each drug was given alone for six nights, with a two-night placebo interval following each phase. Each patient completed an additional placebo phase (up to six nights) before each drug phase. The number of awakenings per night and the sleep latency (time required to fall asleep) were determined from the patients' reports and from the reports of a nurse-observer. Only for oxazepam was the number of patient-reported awakenings per night significantly less than for placebo, although with both oxazepam and flurazepam the awakenings were fewer than with chloral hydrate. According to the patient-reports, sleep latency was significantly lower with flurazepam than with placebo; for oxazepam and chloral hydrate the latencies were not significantly different from those for flurazepam or placebo. Only for oxazepam were the patients' ratings of sleep quality significantly greater than for placebo. The objective assessment of sleep by the nurse-observer usually confirmed the patients' assessments. Morning drowsiness was the most common side effect, reported equally for placebo and for the active drugs. Drowsiness during the day was reported less frequently for oxazepam than for flurazepam, chloral hydrate or placebo. It is concluded that oxazepam is safe and efficacious for the short-term management of insomnia in the elderly."}
{"id": "PMID:27558", "title": "Antibodies of restricted heterogeneity directed against the cardiac glycoside digoxin.", "content": "Intravenous injection of New Zealand White rabbits with type III pneumococcal polysaccharide vaccine conjugated with the cardiac glycoside digoxin resulted in the production of both antidigoxin and anti-type III pneumococcal polysacharide antibodies. Among antisera of 12 rabbits examined during their peak antibody production periods, 1 to 20 mg (mean, 5.4 mg) of antidigoxin antibody could be recovered from 1 ml of serum. Antisera from five of these 12 rabbits contained antidigoxin antibodies of restricted heterogeneity as demonstrated by urea-polyacrylamide disc gel electrophoresis of fully reduced and alkylated antibodies. From the antisera of four of these five rabbits, electrophoretically homogeneous antibodies (1 to 5 mg/ml antiserum) could be isolated by affinity chromatography on ouabain-amine-Sepharose columns. The structural homogeneity of two of these antidigoxin antibodies was confirmed by amino acid sequence analysis of purified light chains through the first hypervariable region. These data suggest that the conjugation of small molecules to bacterial polysaccharide vaccines may provide a general method for synthesis of immunogens that can regularly elicit antihapten antibodies of restricted heterogeneity.", "contents": "Antibodies of restricted heterogeneity directed against the cardiac glycoside digoxin. Intravenous injection of New Zealand White rabbits with type III pneumococcal polysaccharide vaccine conjugated with the cardiac glycoside digoxin resulted in the production of both antidigoxin and anti-type III pneumococcal polysacharide antibodies. Among antisera of 12 rabbits examined during their peak antibody production periods, 1 to 20 mg (mean, 5.4 mg) of antidigoxin antibody could be recovered from 1 ml of serum. Antisera from five of these 12 rabbits contained antidigoxin antibodies of restricted heterogeneity as demonstrated by urea-polyacrylamide disc gel electrophoresis of fully reduced and alkylated antibodies. From the antisera of four of these five rabbits, electrophoretically homogeneous antibodies (1 to 5 mg/ml antiserum) could be isolated by affinity chromatography on ouabain-amine-Sepharose columns. The structural homogeneity of two of these antidigoxin antibodies was confirmed by amino acid sequence analysis of purified light chains through the first hypervariable region. These data suggest that the conjugation of small molecules to bacterial polysaccharide vaccines may provide a general method for synthesis of immunogens that can regularly elicit antihapten antibodies of restricted heterogeneity."}
{"id": "PMID:27560", "title": "Toxicity of Na251CrO4 when used to label rat lymphocytes.", "content": "Lymphocytes preincubated with various activities of Na251CrO4 were tested for their ability to induce a local, popliteal lymph node graft-versus-host (GVH) reaction. Incubation with 100 micronCi of the isotope per ml of cell suspension impaired the GVH activity, 25 micronCi gave a reduced response in 1 out of 3 experiments, whereas 10 micronCi had no effect. The reduced GVH response was due to radiation rather than chemical damage of the cells. Preincubation of the cells with either cold Na2CrO4 or outdated Na251CrO4 with concentrations of Cr identical to the ones used to label cells with 100 micronCi/ml cells did not impair the GVH reactivity. The cellular uptake of Na251CrO4 showed first-order kinetics over wide concentration ranges. Mitomycin C-treated lymphocytes showed a more heavily depressed GVH reactivity than would be expected from their moderately reduced ability to accumulate in the lymph nodes. It is recommended that doses of Na251CrO4 in excess of 10 micronCi/ml cells should not be used for functional studies of lymphocytes.", "contents": "Toxicity of Na251CrO4 when used to label rat lymphocytes. Lymphocytes preincubated with various activities of Na251CrO4 were tested for their ability to induce a local, popliteal lymph node graft-versus-host (GVH) reaction. Incubation with 100 micronCi of the isotope per ml of cell suspension impaired the GVH activity, 25 micronCi gave a reduced response in 1 out of 3 experiments, whereas 10 micronCi had no effect. The reduced GVH response was due to radiation rather than chemical damage of the cells. Preincubation of the cells with either cold Na2CrO4 or outdated Na251CrO4 with concentrations of Cr identical to the ones used to label cells with 100 micronCi/ml cells did not impair the GVH reactivity. The cellular uptake of Na251CrO4 showed first-order kinetics over wide concentration ranges. Mitomycin C-treated lymphocytes showed a more heavily depressed GVH reactivity than would be expected from their moderately reduced ability to accumulate in the lymph nodes. It is recommended that doses of Na251CrO4 in excess of 10 micronCi/ml cells should not be used for functional studies of lymphocytes."}
{"id": "PMID:27561", "title": "Separation and characterization of anti-benzylpenicilloyl (BPO) antibodies. I. Biochemical and biophysical properties of anti-BPO-IgG obtained by affinity and subsequent ion-exchange chromatography.", "content": "Anti-BPO antibodies were purified by means of affinity chromatography using AH-Sepharose 4B coated with covalently bound BPO groups. Specific elution was achieved by the hapten analogue BPO-epsilon-aminocaproic acid (BPO-EACA); desorption of the remaining antibody was performed thereafter by 0.1 M acetic acid. The resulting antibody fractions--hapten-eluted antibody (H-Ab) and acid eluted antibody (A-Ab), respectively--were further separated by ion-exchange chromatography which led to the appearance of 3 subfractions in the case of H-Ab (H1, H2, H3) and 2 subfractions in the case of A-Ab (A1 and A2). In liquid isoelectrofocusing an inhomogeneous pattern resulted. The bulk of antibodies focused between pH 6.5 and 7.0. The average avidity of H-Ab was found to be higher than that of A-Ab suggesting that avidity may influence the elution pattern in affinity chromatography. The hydrophobic influence of the \"spacer\" and/or interactions of antibodies directed against the hydrophobic regions of the BPO group may explain why a considerable part of the antibodies could be recovered from the immunosorbent only by acid elution.", "contents": "Separation and characterization of anti-benzylpenicilloyl (BPO) antibodies. I. Biochemical and biophysical properties of anti-BPO-IgG obtained by affinity and subsequent ion-exchange chromatography. Anti-BPO antibodies were purified by means of affinity chromatography using AH-Sepharose 4B coated with covalently bound BPO groups. Specific elution was achieved by the hapten analogue BPO-epsilon-aminocaproic acid (BPO-EACA); desorption of the remaining antibody was performed thereafter by 0.1 M acetic acid. The resulting antibody fractions--hapten-eluted antibody (H-Ab) and acid eluted antibody (A-Ab), respectively--were further separated by ion-exchange chromatography which led to the appearance of 3 subfractions in the case of H-Ab (H1, H2, H3) and 2 subfractions in the case of A-Ab (A1 and A2). In liquid isoelectrofocusing an inhomogeneous pattern resulted. The bulk of antibodies focused between pH 6.5 and 7.0. The average avidity of H-Ab was found to be higher than that of A-Ab suggesting that avidity may influence the elution pattern in affinity chromatography. The hydrophobic influence of the \"spacer\" and/or interactions of antibodies directed against the hydrophobic regions of the BPO group may explain why a considerable part of the antibodies could be recovered from the immunosorbent only by acid elution."}
{"id": "PMID:27562", "title": "The indirect assay for leukocyte migration inhibitory factor (LIF)--standardization and the effect of pH.", "content": "In the indirect assay for leukocyte migration inhibitory factor (LIF), lymphokine-rich supernatants were obtained by culture of stimulated lymphocytes and then tested for LIF activity in agarose plates using purified granulocytes as target cells. Studies on the standardization of the conditions under which LIF acts on the target cells are described, with emphasis on the use of \"standard\" supernatants of known LIF activity and the influence of pH on the action of LIF and the sensitivity of the assay. The observation that LIF activity is reduced when the ambient pH falls below 7.2 is suggested as an explanation firstly for the \"escape\" phenomenon seen particularly in capillary tube assays for LIF, and secondly for the reduced sensitivity of the capillarly tube assay in comparison with the corresponding agarose plate assay.", "contents": "The indirect assay for leukocyte migration inhibitory factor (LIF)--standardization and the effect of pH. In the indirect assay for leukocyte migration inhibitory factor (LIF), lymphokine-rich supernatants were obtained by culture of stimulated lymphocytes and then tested for LIF activity in agarose plates using purified granulocytes as target cells. Studies on the standardization of the conditions under which LIF acts on the target cells are described, with emphasis on the use of \"standard\" supernatants of known LIF activity and the influence of pH on the action of LIF and the sensitivity of the assay. The observation that LIF activity is reduced when the ambient pH falls below 7.2 is suggested as an explanation firstly for the \"escape\" phenomenon seen particularly in capillary tube assays for LIF, and secondly for the reduced sensitivity of the capillarly tube assay in comparison with the corresponding agarose plate assay."}
{"id": "PMID:27565", "title": "Studies on the characterization of isolated renin-containing granules: the storage form of renin.", "content": "Renin-containing granules isolated by isopycnic zonal centrifugation were partially characterized biochemically. Extracts of the granules were found to have a dual pH optimum at 5.5-6.0 and 7.0-7.5 and possess linear time-dependence of product formation when reacted with homologous renin substrate. Extracts also possessed a first order reaction constant of 0.713 X 10(-2). Treatment of the extracts with ammonium sulfate increased the velocity of the renin/renin substrate reaction though it continued to be linear with respect to time. This partially purified renin preparation was found to have a Km=3.9 X 10(3) ng/ml. Gel filtration of this preparation of renin demonstrated the presence of an active protein with renin activity and a molecular weight of 59,000 daltons in addition to an inactive protein of molecular weight 13, 750 daltons which may be a potential inhibitor of the renin/renin substrate reaction. The former protein or \"big renin\" may be the storage form or porhormone state of renin within the renin-containing granules of the juxtaglomerular cells.", "contents": "Studies on the characterization of isolated renin-containing granules: the storage form of renin. Renin-containing granules isolated by isopycnic zonal centrifugation were partially characterized biochemically. Extracts of the granules were found to have a dual pH optimum at 5.5-6.0 and 7.0-7.5 and possess linear time-dependence of product formation when reacted with homologous renin substrate. Extracts also possessed a first order reaction constant of 0.713 X 10(-2). Treatment of the extracts with ammonium sulfate increased the velocity of the renin/renin substrate reaction though it continued to be linear with respect to time. This partially purified renin preparation was found to have a Km=3.9 X 10(3) ng/ml. Gel filtration of this preparation of renin demonstrated the presence of an active protein with renin activity and a molecular weight of 59,000 daltons in addition to an inactive protein of molecular weight 13, 750 daltons which may be a potential inhibitor of the renin/renin substrate reaction. The former protein or \"big renin\" may be the storage form or porhormone state of renin within the renin-containing granules of the juxtaglomerular cells."}
{"id": "PMID:27568", "title": "Enrichment of in vitro and in vivo immunologic activity of purified fractions of calf thymic hormone.", "content": "Thymus humoral factor (THF), a thymus hormone which participates in the processes leading to acquisition of immunocompetence of lymphoid cells has been isolated in our laboratory by a stepwise gel filtration through various Sephadex columns. THF so isolated appears to be a polypeptide of 3,000 mol wt which contains approximately 30 amino acid residues. Here we have tested the biological activity of THF fractions of successive degrees of purity upon lymphoid cells from both intact and neonatally thymectomized mice. The lymphoid cell populations were treated with the various THF fractions by in vitro incubation for a short time and by repeated injection in vivo. The treated cells evidenced increased ability to react in the graft-versus-host assay in vivo and in mixed lymphocyte cultures in vitro concomitantly with the rise of intracellular cAMP. On the other hand no activity whatsoever was shown by any of the control materials tested. These bioassays permitted isolation of fractions progressively more active than the original crude dialyzate of thymus extract tested. Thus the active peptide component of THF eluted from DEAE Sephadex A-25 column was estimated to be 2 X 10(4)-fold more active than the crude dialyzate of thymus extract which served as a starting material.", "contents": "Enrichment of in vitro and in vivo immunologic activity of purified fractions of calf thymic hormone. Thymus humoral factor (THF), a thymus hormone which participates in the processes leading to acquisition of immunocompetence of lymphoid cells has been isolated in our laboratory by a stepwise gel filtration through various Sephadex columns. THF so isolated appears to be a polypeptide of 3,000 mol wt which contains approximately 30 amino acid residues. Here we have tested the biological activity of THF fractions of successive degrees of purity upon lymphoid cells from both intact and neonatally thymectomized mice. The lymphoid cell populations were treated with the various THF fractions by in vitro incubation for a short time and by repeated injection in vivo. The treated cells evidenced increased ability to react in the graft-versus-host assay in vivo and in mixed lymphocyte cultures in vitro concomitantly with the rise of intracellular cAMP. On the other hand no activity whatsoever was shown by any of the control materials tested. These bioassays permitted isolation of fractions progressively more active than the original crude dialyzate of thymus extract tested. Thus the active peptide component of THF eluted from DEAE Sephadex A-25 column was estimated to be 2 X 10(4)-fold more active than the crude dialyzate of thymus extract which served as a starting material."}
{"id": "PMID:27569", "title": "Determination of perazine serum levels by gas liquid chromatography under clinical routine conditions.", "content": "A quantitative gas liquid chromatographic method for the determination of serum levels of perazine (10-[3'-(1''-methyl-4''-piperazinyl)-propyl]-phenothiazine) is described. Perazine is used as a neuroleptic drug. The main problem consists in optimizing the chromatographic system. A sensitivity of appr. 60--150 nmol/1 (20--50 microgram/1) serum is achieved. Examples of optimization, analyses with patient samples, and the reproducibility of the results are presented.", "contents": "Determination of perazine serum levels by gas liquid chromatography under clinical routine conditions. A quantitative gas liquid chromatographic method for the determination of serum levels of perazine (10-[3'-(1''-methyl-4''-piperazinyl)-propyl]-phenothiazine) is described. Perazine is used as a neuroleptic drug. The main problem consists in optimizing the chromatographic system. A sensitivity of appr. 60--150 nmol/1 (20--50 microgram/1) serum is achieved. Examples of optimization, analyses with patient samples, and the reproducibility of the results are presented."}
{"id": "PMID:27570", "title": "Increased urinary excretion of keratan sulfate in fucosidosis.", "content": "In two children exhibiting the clinical symptoms of fucosidosis, the diagnosis was biochemically ascertained by the demonstration of a profound altpha-L-fucosidase deficiency in cultured skin fibroblasts. The non-dialysed urines of these fucosidosis patients were separated into two fractions by chromatography on Biogel P-2. The first fraction containing the glycosaminoglycans was further fractionated on Dowex 1 X 2 by stepwise elution with increasing NaCl concentrations. Keratan sulfate-chondroitin sulfates attached to the same peptide core were assayed and characterised mainly in the fractions eluted with 1.25, 1.5, 2.0 and 3.0 mol/1 NaCl. Whereas the excretion of normal children of the same age was found to be 0.77 mumol glucosamine equivalents per day in the 2 mol/1 and 3 mol/1 NaCl fraction, the two patients excreted 6.7 (M. C.) and 3.5 (M. S.) mumol glucosamine equivalents per day, respectively. Since keratan sulfate contains alpha-fucose at the non-reducing terminal, this increase in excretion of long chain keratan sulfate in fucosidosis could result from impaired degradation of keratan sulfate, due to the alpha-fucosidase deficiency.", "contents": "Increased urinary excretion of keratan sulfate in fucosidosis. In two children exhibiting the clinical symptoms of fucosidosis, the diagnosis was biochemically ascertained by the demonstration of a profound altpha-L-fucosidase deficiency in cultured skin fibroblasts. The non-dialysed urines of these fucosidosis patients were separated into two fractions by chromatography on Biogel P-2. The first fraction containing the glycosaminoglycans was further fractionated on Dowex 1 X 2 by stepwise elution with increasing NaCl concentrations. Keratan sulfate-chondroitin sulfates attached to the same peptide core were assayed and characterised mainly in the fractions eluted with 1.25, 1.5, 2.0 and 3.0 mol/1 NaCl. Whereas the excretion of normal children of the same age was found to be 0.77 mumol glucosamine equivalents per day in the 2 mol/1 and 3 mol/1 NaCl fraction, the two patients excreted 6.7 (M. C.) and 3.5 (M. S.) mumol glucosamine equivalents per day, respectively. Since keratan sulfate contains alpha-fucose at the non-reducing terminal, this increase in excretion of long chain keratan sulfate in fucosidosis could result from impaired degradation of keratan sulfate, due to the alpha-fucosidase deficiency."}
{"id": "PMID:27571", "title": "Comments on \"Studies of the interaction of psychological and pharmacological determinants of smoking\" by Schachter et al.", "content": "The work by Schachter and his colleagues on the psychological and pharmacological determinants of smoking is reviewed. The experiemental procedures are critically examined, and some are judged to be in violation of ethical standards for the conduct of research with human participants. Questions are raised concerning matters of informed consent, the description of debriefing procedures, and use of the college classroom as a psychological laboratory.", "contents": "Comments on \"Studies of the interaction of psychological and pharmacological determinants of smoking\" by Schachter et al. The work by Schachter and his colleagues on the psychological and pharmacological determinants of smoking is reviewed. The experiemental procedures are critically examined, and some are judged to be in violation of ethical standards for the conduct of research with human participants. Questions are raised concerning matters of informed consent, the description of debriefing procedures, and use of the college classroom as a psychological laboratory."}
{"id": "PMID:27572", "title": "Purification and properties of glutamate dehydrogenase from the mantle muscle of the squid, Loligo pealeii. Role of the enzyme in energy production from amino acids.", "content": "1. The activity of glutamate dehydrogenase was measured in the tissues of the squid, Loligo pealeii. The enzyme occurs in high activity in digestive pouch, systemic heart, and all muscle tissues. 2. Glutamate dehydrogenase from mantle muscle is located intra-mitochondrially, has a molecular weight of 310,000, and is electrophoretically similar to the enzyme from all other squid tissues. 3. The enzyme from mantle muscle  was purified 40-fold by elution from DEAE-cellulose and used for kinetic studies. The enzyme is NAD+-specific, activated by ADP, AMP, and leucine, and inhibited by GTP, GDP, ATP, and reaction products (in particular NADH). 4. Squid glutamate dehydrogenase shows an almost absolute dependence on ADP. The purified enzyme is activated over 100-fold by saturating concentrations of ADP (Ka = 0,75 7M); The pH optima are also altered significantly by ADP. 5. The enzyme appears to be kinetically adapted to favour glutamate oxidation in comparison to glutamate dehydrogenase from other resources. The evidence indicates that the primary role of glutamate dehydrogenase in squid mantle muscle is in regulating the catabolism of amino acids for energy production.", "contents": "Purification and properties of glutamate dehydrogenase from the mantle muscle of the squid, Loligo pealeii. Role of the enzyme in energy production from amino acids. 1. The activity of glutamate dehydrogenase was measured in the tissues of the squid, Loligo pealeii. The enzyme occurs in high activity in digestive pouch, systemic heart, and all muscle tissues. 2. Glutamate dehydrogenase from mantle muscle is located intra-mitochondrially, has a molecular weight of 310,000, and is electrophoretically similar to the enzyme from all other squid tissues. 3. The enzyme from mantle muscle  was purified 40-fold by elution from DEAE-cellulose and used for kinetic studies. The enzyme is NAD+-specific, activated by ADP, AMP, and leucine, and inhibited by GTP, GDP, ATP, and reaction products (in particular NADH). 4. Squid glutamate dehydrogenase shows an almost absolute dependence on ADP. The purified enzyme is activated over 100-fold by saturating concentrations of ADP (Ka = 0,75 7M); The pH optima are also altered significantly by ADP. 5. The enzyme appears to be kinetically adapted to favour glutamate oxidation in comparison to glutamate dehydrogenase from other resources. The evidence indicates that the primary role of glutamate dehydrogenase in squid mantle muscle is in regulating the catabolism of amino acids for energy production."}
{"id": "PMID:27574", "title": "Ionic blockage of the light-regulated sodium channels in isolated rod outer segments.", "content": "We have investigated, with osmotic techniques, the light-regulated Na+ channels in rod outer segments (ROS) and ROS fragments freshly isolated from the frog retina. Values of Na+ permeability (PNa) similar to those observed electrophysiologically in the retina were observed using the osmotic technique (continuous flow) described by Korenbrot and Cone. In the other osmotic techniques that we explored, PNa was greatly diminished, if not completely suppressed; however, we found with these techniques that antioxidant conditions (N2 atmosphere or EDTA) significantly increased PNa, suggesting that the Na+ channels are highly sensitivive to membrane oxidation. Using the continuous flow technique, we investigated the H+ and Ca++ dependence of the Na+ channels and found that both of these ions, at micromolar activities, can block the channels. Raising the external H+ activity decreases PNa (reversibly) in a single \"sigmoidal\" response with an apparent pKa of 5.8. Similarly, in the presence of the ionophores X537A or A23187 which allow equilibration of Ca++ across membranes, the Na+ channels are blocked when the external Ca++ activity is increased from 10(-7) to 10(-5) M. This high sensitivity to both H+ and Ca++ ions suggests that high field strength anionic sites may exist in or near the Na+ channels and that the channels are blocked when these sites bind H+ or Ca++ ions.", "contents": "Ionic blockage of the light-regulated sodium channels in isolated rod outer segments. We have investigated, with osmotic techniques, the light-regulated Na+ channels in rod outer segments (ROS) and ROS fragments freshly isolated from the frog retina. Values of Na+ permeability (PNa) similar to those observed electrophysiologically in the retina were observed using the osmotic technique (continuous flow) described by Korenbrot and Cone. In the other osmotic techniques that we explored, PNa was greatly diminished, if not completely suppressed; however, we found with these techniques that antioxidant conditions (N2 atmosphere or EDTA) significantly increased PNa, suggesting that the Na+ channels are highly sensitivive to membrane oxidation. Using the continuous flow technique, we investigated the H+ and Ca++ dependence of the Na+ channels and found that both of these ions, at micromolar activities, can block the channels. Raising the external H+ activity decreases PNa (reversibly) in a single \"sigmoidal\" response with an apparent pKa of 5.8. Similarly, in the presence of the ionophores X537A or A23187 which allow equilibration of Ca++ across membranes, the Na+ channels are blocked when the external Ca++ activity is increased from 10(-7) to 10(-5) M. This high sensitivity to both H+ and Ca++ ions suggests that high field strength anionic sites may exist in or near the Na+ channels and that the channels are blocked when these sites bind H+ or Ca++ ions."}
{"id": "PMID:27575", "title": "Nitrogen regulation of glutamine synthetase in Neurospora crassa.", "content": "A higher activity of glutamine synthetase (EC 6.3.1.2) was found in Neurospora crassa when NH4+ was limiting as nitrogen source than when glutamate was limiting. When glutamate, glutamine or NH4+ were in excess, a lower activity was found. Immunological titration and sucrose gradient sedimentation of the enzyme established that under all these conditions enzyme activity corresponded to enzyme concentration and that the octamer was the predominant oligomeric form. When N. crassa was shifted from nitrogen-limiting substrates to excess product as nitrogen source, the concentration of glutamine synthetase was adjusted with kinetics that closely followed dilution by growth. When grown on limiting amounts of glutamate, a lower oligomer was present in addition to the octameric form of the enzyme. When the culture was shifted to excess NH4+, glutamine accululated at a high rate; nevertheless, there was only a slow decrease in enzyme activity and no modification of the oligomeric pattern.", "contents": "Nitrogen regulation of glutamine synthetase in Neurospora crassa. A higher activity of glutamine synthetase (EC 6.3.1.2) was found in Neurospora crassa when NH4+ was limiting as nitrogen source than when glutamate was limiting. When glutamate, glutamine or NH4+ were in excess, a lower activity was found. Immunological titration and sucrose gradient sedimentation of the enzyme established that under all these conditions enzyme activity corresponded to enzyme concentration and that the octamer was the predominant oligomeric form. When N. crassa was shifted from nitrogen-limiting substrates to excess product as nitrogen source, the concentration of glutamine synthetase was adjusted with kinetics that closely followed dilution by growth. When grown on limiting amounts of glutamate, a lower oligomer was present in addition to the octameric form of the enzyme. When the culture was shifted to excess NH4+, glutamine accululated at a high rate; nevertheless, there was only a slow decrease in enzyme activity and no modification of the oligomeric pattern."}
{"id": "PMID:27576", "title": "Biochemical and biophysical characterization of light and heavy density hepatitis A virus particles: evidence HAV is an RNA virus.", "content": "Heavy density HAV was also shown to be sensitive to low concentrations of RNase. The results of these biophysical and biochemical studies strongly support the notion HAV is an enterovirus.", "contents": "Biochemical and biophysical characterization of light and heavy density hepatitis A virus particles: evidence HAV is an RNA virus. Heavy density HAV was also shown to be sensitive to low concentrations of RNase. The results of these biophysical and biochemical studies strongly support the notion HAV is an enterovirus."}
{"id": "PMID:27577", "title": "Behavioral rhythms in schizophrenia.", "content": "Daily behavioral observations were made for several years on 10 male schizophrenic patients and on three male patients with organic brain disorders. Analysis of these data showed strong cyclic components in the five schizophrenic patients with predominantly hebephrenic symptomatology. Period lengths noted were about 2 days, 5 to 6 days, 30 days, and a longer cycle of 40 to 100 days duration. Antipsychotic medications appear to have a suppressant effect, but tricyclic antidepressants may enhance pre-existing rhythms.", "contents": "Behavioral rhythms in schizophrenia. Daily behavioral observations were made for several years on 10 male schizophrenic patients and on three male patients with organic brain disorders. Analysis of these data showed strong cyclic components in the five schizophrenic patients with predominantly hebephrenic symptomatology. Period lengths noted were about 2 days, 5 to 6 days, 30 days, and a longer cycle of 40 to 100 days duration. Antipsychotic medications appear to have a suppressant effect, but tricyclic antidepressants may enhance pre-existing rhythms."}
{"id": "PMID:27578", "title": "Clinical course of adult metachromatic leukodystrophy presenting as schizophrenia. A report of two living cases in siblings.", "content": "Adult metachromatic leukodystrophy is a demyelinating disease due to an inherited lack of arylsulfatase A activity. The purpose of this paper is to present the characteristics of this disorder as they occurred chronologically in two siblings, prior to and subsequent to the appearance of gross neurological deficits. A deficit in spatial relationships, as contrasted with verbal abilities, was observed initially in both cases at age 13. Initial psychiatric symptoms were noted at age 16 and 18, with both patients being diagnosed subsequently as schizophrenic. Gross neurological deficits were observed 2 and 13 years, respectively, after the appearance of psychiatric symptoms. A deficit in spatial relationships may be a very sensitive early indicator of adult metachromatic leukodystrophy.", "contents": "Clinical course of adult metachromatic leukodystrophy presenting as schizophrenia. A report of two living cases in siblings. Adult metachromatic leukodystrophy is a demyelinating disease due to an inherited lack of arylsulfatase A activity. The purpose of this paper is to present the characteristics of this disorder as they occurred chronologically in two siblings, prior to and subsequent to the appearance of gross neurological deficits. A deficit in spatial relationships, as contrasted with verbal abilities, was observed initially in both cases at age 13. Initial psychiatric symptoms were noted at age 16 and 18, with both patients being diagnosed subsequently as schizophrenic. Gross neurological deficits were observed 2 and 13 years, respectively, after the appearance of psychiatric symptoms. A deficit in spatial relationships may be a very sensitive early indicator of adult metachromatic leukodystrophy."}
{"id": "PMID:27579", "title": "Neurobiology of Polyorchis. I. Function of effector systems.", "content": "The electrical correlates of activity in the effector systems responsible for swimming, crumpling and postural changes have been recorded in the anthomedusan Polyorchis penicillatus. Motor spikes (pre-swim pulses), that initiate swimming contractions, appear without delay at distant sites on the inner nerve-ring in unstimulated preparations. Levels of Mg++ anaesthesia which block the neuromuscular junctions between PSP giant neurons and swimming muscle do not affect PSP activity. Swimming muscle potentials can be recorded from subumbrella and velar muscle sheets using extra- and intracellular electrodes. These action potentials have a distinct plateau and are propagated in a myoid fashion. Resting potentials average -70 mV with spikes overshooting zero by some 62 mV. The effects of repetitive stimulation are described. Extracellular recordings indicate that neuronal pathways may play a major role in mediating crumpling, unlike many other species where epithelial pathways are more important. Endodermal spikes recorded intracellularly from the radial and ring canals have amplitudes of some 92 mV arising from resting potentials that average -55 mV. Repetitive stimulation causes a decrease in amplitude and increase in duration of epithelial action potentials. Tentacle length is controlled by a pacemaker system located in both nerve rings. The frequency of spikes (PTPs) generated by this system determines the length and tonus of tentacles. The neuromuscular junctions between the motor neurons and tentacle muscle are Mg++ sensitive and show facilitating properties.", "contents": "Neurobiology of Polyorchis. I. Function of effector systems. The electrical correlates of activity in the effector systems responsible for swimming, crumpling and postural changes have been recorded in the anthomedusan Polyorchis penicillatus. Motor spikes (pre-swim pulses), that initiate swimming contractions, appear without delay at distant sites on the inner nerve-ring in unstimulated preparations. Levels of Mg++ anaesthesia which block the neuromuscular junctions between PSP giant neurons and swimming muscle do not affect PSP activity. Swimming muscle potentials can be recorded from subumbrella and velar muscle sheets using extra- and intracellular electrodes. These action potentials have a distinct plateau and are propagated in a myoid fashion. Resting potentials average -70 mV with spikes overshooting zero by some 62 mV. The effects of repetitive stimulation are described. Extracellular recordings indicate that neuronal pathways may play a major role in mediating crumpling, unlike many other species where epithelial pathways are more important. Endodermal spikes recorded intracellularly from the radial and ring canals have amplitudes of some 92 mV arising from resting potentials that average -55 mV. Repetitive stimulation causes a decrease in amplitude and increase in duration of epithelial action potentials. Tentacle length is controlled by a pacemaker system located in both nerve rings. The frequency of spikes (PTPs) generated by this system determines the length and tonus of tentacles. The neuromuscular junctions between the motor neurons and tentacle muscle are Mg++ sensitive and show facilitating properties."}
{"id": "PMID:27590", "title": "Cytochemical demonstration of adenylate and guanylate cyclases in vascular smooth muscle of circle of Willis.", "content": "The cytochemical localization of adenylate cyclase and guanylate cyclase was studied in the arteries of the circle of Willis in dogs. The reaction products of both adenylate and guanylate cyclases were similarly distributed and selectively localized predominantly adjacent to sarcoplasmic reticulum and sparsely to mitochondria and outer nuclear membranes of vascular smooth muscles. The observations could suggest a close association of the intracellular localizations of both cyclases and the intracellular calcium storage sites, and ultimately contribute to our complete understanding of regulation of cerebral blood flow and vasospasm.", "contents": "Cytochemical demonstration of adenylate and guanylate cyclases in vascular smooth muscle of circle of Willis. The cytochemical localization of adenylate cyclase and guanylate cyclase was studied in the arteries of the circle of Willis in dogs. The reaction products of both adenylate and guanylate cyclases were similarly distributed and selectively localized predominantly adjacent to sarcoplasmic reticulum and sparsely to mitochondria and outer nuclear membranes of vascular smooth muscles. The observations could suggest a close association of the intracellular localizations of both cyclases and the intracellular calcium storage sites, and ultimately contribute to our complete understanding of regulation of cerebral blood flow and vasospasm."}
{"id": "PMID:27591", "title": "Abnormal cellular copper metabolism in the blotchy mouse.", "content": "Defective copper metabolism was demonstrated in male mice bearing the blotchy (Moblo/y) allele at the mottled locus on the X-chromosome. Copper absorption from the gut was only 64% of that found in normal mice and hepatic copper levels were only 56% of the controls. Ceruloplasmin and heart cytochrome c oxidase activities were normal, yet lysyl oxidase activity from cultured fibroblasts was only 45% of control levels. Copper accumulated in fibroblasts cultured from these mutants to values that were five times normal. The accumulation of copper in the fibroblasts was associated with a protein of approximately 12,000 molecular weight.", "contents": "Abnormal cellular copper metabolism in the blotchy mouse. Defective copper metabolism was demonstrated in male mice bearing the blotchy (Moblo/y) allele at the mottled locus on the X-chromosome. Copper absorption from the gut was only 64% of that found in normal mice and hepatic copper levels were only 56% of the controls. Ceruloplasmin and heart cytochrome c oxidase activities were normal, yet lysyl oxidase activity from cultured fibroblasts was only 45% of control levels. Copper accumulated in fibroblasts cultured from these mutants to values that were five times normal. The accumulation of copper in the fibroblasts was associated with a protein of approximately 12,000 molecular weight."}
{"id": "PMID:27592", "title": "Loss of in vitro inactivation of rat liver tyrosine aminotransferase with dietary vitamin B6 restriction.", "content": "Tyrosine aminotransferase, in the presence of 8 mM L-cysteine, is inactivated in incubated liver homogenates prepared from normal rats, but not in those from rats deprived of vitamin B6. In this study we fed rats a diet deficient in vitamin B6 to determine the length of time required for in vitro inactivating activity to be lost from liver homogenates. After 2 weeks, the half-life of tyrosine aminotransferase in liver homogenates from vitamin B6-deficient rats was 5.9 hours, and from control rats, 1.8 hours. After 3 weeks, tyrosine aminotransferase was no longer inactivated in homogenates prepared from livers of deficient rats. The pyridoxal phosphate (PLP) concentration of plasma from rats fed the vitamin B6-deficient diet dropped from 89 ng/ml to 14 ng/ml after 1 week and to 7 ng/ml after 2 weeks. In 5 weeks the PLP concentration of liver from vitamin B6-adequate rats increased from 2.9 microgram/g to 6.6 microgram/g while in deficient rats it dropped to 2 microgram/g. The loss of tyrosine aminotransferase inactivating activity in the livers of vitamin B6-deficient rats occurred at approximately the same time that the concentration of PLP in the livers of rats fed the two diets began to show marked differences.", "contents": "Loss of in vitro inactivation of rat liver tyrosine aminotransferase with dietary vitamin B6 restriction. Tyrosine aminotransferase, in the presence of 8 mM L-cysteine, is inactivated in incubated liver homogenates prepared from normal rats, but not in those from rats deprived of vitamin B6. In this study we fed rats a diet deficient in vitamin B6 to determine the length of time required for in vitro inactivating activity to be lost from liver homogenates. After 2 weeks, the half-life of tyrosine aminotransferase in liver homogenates from vitamin B6-deficient rats was 5.9 hours, and from control rats, 1.8 hours. After 3 weeks, tyrosine aminotransferase was no longer inactivated in homogenates prepared from livers of deficient rats. The pyridoxal phosphate (PLP) concentration of plasma from rats fed the vitamin B6-deficient diet dropped from 89 ng/ml to 14 ng/ml after 1 week and to 7 ng/ml after 2 weeks. In 5 weeks the PLP concentration of liver from vitamin B6-adequate rats increased from 2.9 microgram/g to 6.6 microgram/g while in deficient rats it dropped to 2 microgram/g. The loss of tyrosine aminotransferase inactivating activity in the livers of vitamin B6-deficient rats occurred at approximately the same time that the concentration of PLP in the livers of rats fed the two diets began to show marked differences."}
{"id": "PMID:27593", "title": "Characterization of thiamine diphosphatase in rat small intestine.", "content": "The properties of thiamine diphosphatase (TDPase) and p-nitrophenylphosphatase (p-NPPase) in rat small intestine were investigated. TDPase activity, like p-NPPase activity, was high in the mucosa and in the proximal region. Both activities were high in the membrane-associated fractions of the duodenal mucosa. Furthermore, TDPase had the same properties as intestinal alkaline phosphatase (al-Pase). These results suggest that thiamine diphosphate (TDP) and p-nitrophenylphosphate (p-NPP) are hydrolyzed by a single enzyme, al-Pase, in the intestine.", "contents": "Characterization of thiamine diphosphatase in rat small intestine. The properties of thiamine diphosphatase (TDPase) and p-nitrophenylphosphatase (p-NPPase) in rat small intestine were investigated. TDPase activity, like p-NPPase activity, was high in the mucosa and in the proximal region. Both activities were high in the membrane-associated fractions of the duodenal mucosa. Furthermore, TDPase had the same properties as intestinal alkaline phosphatase (al-Pase). These results suggest that thiamine diphosphate (TDP) and p-nitrophenylphosphate (p-NPP) are hydrolyzed by a single enzyme, al-Pase, in the intestine."}
{"id": "PMID:27595", "title": "The isolation and characterization of a trypsin inhibitor from Kintoki bean (Phaseolus vulgaris).", "content": "A trypsin inhibitor was isolated from beans of Phaseolus vulgaris, cultivar. Kintoki, and the specific activity increased 200 times as high as that of the crude extract. It was homogeneous on several electrophoreses and the molecular weight was about 13,000. The amino acid composition was characterized by high ratios of cystine, aspartic acid, and serine. It inhibited trypsin in a molar ratio of 1 : 1 and alpha-chymotrypsin in a molar ratio of 2 : 1. It, however, inhibited neither pepsin nor pronase. It was relatively stable to heat treatment in the acidic medium, but not in the alkaline medium. Neither pepsin nor pronase destroyed the inhibitory function.", "contents": "The isolation and characterization of a trypsin inhibitor from Kintoki bean (Phaseolus vulgaris). A trypsin inhibitor was isolated from beans of Phaseolus vulgaris, cultivar. Kintoki, and the specific activity increased 200 times as high as that of the crude extract. It was homogeneous on several electrophoreses and the molecular weight was about 13,000. The amino acid composition was characterized by high ratios of cystine, aspartic acid, and serine. It inhibited trypsin in a molar ratio of 1 : 1 and alpha-chymotrypsin in a molar ratio of 2 : 1. It, however, inhibited neither pepsin nor pronase. It was relatively stable to heat treatment in the acidic medium, but not in the alkaline medium. Neither pepsin nor pronase destroyed the inhibitory function."}
{"id": "PMID:27596", "title": "Effects of various metabolites (sugars, carboxylic acids and alcohols) on riboflavin formation in non-growing cells of Ashbya gossypii.", "content": "The effects of various sugars and sugar derivatives on flavinogenesis were examined using non-growing cells of a high flavinogenic mold, Ashbya gossypii. Glucose, fructose and galactose were found to be the most stimulative. Glycerol and glucono-delta-lactone were less stimulative; next in order were n-propanol, n-butanol, glycols and butanediols, which were likewise effective; acetate, lactate and pyruvate were slightly stimulative. In contrast, ribose, xylose, arabinose, ribitol, citrate, succinate, oxaloacetate, glyoxylate and malate were rather inhibitory, in additions at 1.0%. Among these compounds, ethanol (1%) greatly stimulated  riboflavin formation. Maximum flavinogenesis with the above stimulants was attained by the additions of 1% ethanol, 1.25--3.0% glucose, 1.25% glycerol, 4.0--6.0% propane and butanediols, 1.0% pyruvate and 0.9% acetate after 37 hr incubation, respectively. These compounds inhibited flavinogenesis with increasing concentrations above their optimum concentrations. The stimulation effect of ethanol far exceeded those of other stimulants but ethanol had almost no effect on growth and pH values during incubation. With the addition of ethanol (1%) during incubation, maximum formation (1,776 microgram/g wet mycelia) of riboflavin was achieved when added at the start of incubation and the most effective utilization was observed when added at the logarithmic phase of flavinogenesis, although the maximum formation of riboflavin in the latter case was much lower than in the former case. The relation of sugar metabolism, especially ethanol metabolism, to flavinogenesis was discussed with the flavinogenic activities of these additives.", "contents": "Effects of various metabolites (sugars, carboxylic acids and alcohols) on riboflavin formation in non-growing cells of Ashbya gossypii. The effects of various sugars and sugar derivatives on flavinogenesis were examined using non-growing cells of a high flavinogenic mold, Ashbya gossypii. Glucose, fructose and galactose were found to be the most stimulative. Glycerol and glucono-delta-lactone were less stimulative; next in order were n-propanol, n-butanol, glycols and butanediols, which were likewise effective; acetate, lactate and pyruvate were slightly stimulative. In contrast, ribose, xylose, arabinose, ribitol, citrate, succinate, oxaloacetate, glyoxylate and malate were rather inhibitory, in additions at 1.0%. Among these compounds, ethanol (1%) greatly stimulated  riboflavin formation. Maximum flavinogenesis with the above stimulants was attained by the additions of 1% ethanol, 1.25--3.0% glucose, 1.25% glycerol, 4.0--6.0% propane and butanediols, 1.0% pyruvate and 0.9% acetate after 37 hr incubation, respectively. These compounds inhibited flavinogenesis with increasing concentrations above their optimum concentrations. The stimulation effect of ethanol far exceeded those of other stimulants but ethanol had almost no effect on growth and pH values during incubation. With the addition of ethanol (1%) during incubation, maximum formation (1,776 microgram/g wet mycelia) of riboflavin was achieved when added at the start of incubation and the most effective utilization was observed when added at the logarithmic phase of flavinogenesis, although the maximum formation of riboflavin in the latter case was much lower than in the former case. The relation of sugar metabolism, especially ethanol metabolism, to flavinogenesis was discussed with the flavinogenic activities of these additives."}
{"id": "PMID:27603", "title": "Multiple-scored tablets. Weight and content uniformity of subdivisions and distribution of active constituent within and between tablets.", "content": "Using three brands of multiple-scored levodopa tablets, B.P. (500 mg) and one brand of sulphamethoxypyridazine tablets B.P. (500 mg) the weight and content uniformity of the subdivisions has been examined. It is shown that quartering of such tablets can result in subunits which do not conform to recognized standards of weight uniformity, and in some instances content uniformity may be questionable. The homogeneity of distribution of active constituent between tablets has been determined and compared with that within tablets (between quarters of individual tablets). Statistical evaluation of the results is presented.", "contents": "Multiple-scored tablets. Weight and content uniformity of subdivisions and distribution of active constituent within and between tablets. Using three brands of multiple-scored levodopa tablets, B.P. (500 mg) and one brand of sulphamethoxypyridazine tablets B.P. (500 mg) the weight and content uniformity of the subdivisions has been examined. It is shown that quartering of such tablets can result in subunits which do not conform to recognized standards of weight uniformity, and in some instances content uniformity may be questionable. The homogeneity of distribution of active constituent between tablets has been determined and compared with that within tablets (between quarters of individual tablets). Statistical evaluation of the results is presented."}
{"id": "PMID:27604", "title": "The effect of repeated administration of diftalone on enzyme induction.", "content": "Plasma concentrations of diftalone have been examined in normal volunteers after a single dose (500 mg) and after 500 mg doses given twice daily for one week. An increase in post dosing urinary excretion of D-glucaric acid showed a correlation with the ratio of calculated to observed areas under the plasma concentration, time curve following the final dose in the multiple dosing studies, indicating that hepatic microsomal enzymes are induced after repeated administration of the drug. Single dose studies in the presence of aluminium hydroxide and sodium bicarbonate showed that the antacids had no significant effect on the absorption of diftalone.", "contents": "The effect of repeated administration of diftalone on enzyme induction. Plasma concentrations of diftalone have been examined in normal volunteers after a single dose (500 mg) and after 500 mg doses given twice daily for one week. An increase in post dosing urinary excretion of D-glucaric acid showed a correlation with the ratio of calculated to observed areas under the plasma concentration, time curve following the final dose in the multiple dosing studies, indicating that hepatic microsomal enzymes are induced after repeated administration of the drug. Single dose studies in the presence of aluminium hydroxide and sodium bicarbonate showed that the antacids had no significant effect on the absorption of diftalone."}
{"id": "PMID:27605", "title": "The determination of sulphoxide in degraded phenothiazine formulations by difference spectrophotometry.", "content": "A method is described for the assay of phenothiazine sulphoxides which may be formed in phenothiazine formulations during storage under unfavourable conditions. The assay is based upon the measurement of difference absorbance of the sulphoxide solution in 0.2 M hydrochloric acid relative to an equimolar solution reduced with zinc dust. A solvent extraction procedure avoids interference from colouring agents and coloured photolytic breakdown products of the phenothiazines. The assay is specific in the presence of intact drug, sulphone and co-formulated drugs for the formulations examined and is sensitive to 0.5% of the total phenothiazine present as sulphoxide. Many aqueous formulations stored in partially filled containers have been shown to contain up to 31.5% of the total phenothiazine as sulphoxide.", "contents": "The determination of sulphoxide in degraded phenothiazine formulations by difference spectrophotometry. A method is described for the assay of phenothiazine sulphoxides which may be formed in phenothiazine formulations during storage under unfavourable conditions. The assay is based upon the measurement of difference absorbance of the sulphoxide solution in 0.2 M hydrochloric acid relative to an equimolar solution reduced with zinc dust. A solvent extraction procedure avoids interference from colouring agents and coloured photolytic breakdown products of the phenothiazines. The assay is specific in the presence of intact drug, sulphone and co-formulated drugs for the formulations examined and is sensitive to 0.5% of the total phenothiazine present as sulphoxide. Many aqueous formulations stored in partially filled containers have been shown to contain up to 31.5% of the total phenothiazine as sulphoxide."}
{"id": "PMID:27606", "title": "Species differences in the in vitro metabolic reduction of the amphetamine metabolite, 1-phenyl-2-propanone.", "content": "Marked differences were observed, in the ability of fortified 9000 g liver homogenate supernatants from three species to reduce 1-phenyl-2-propanone to the corresponding alcohol. This metabolic keto-reduction was negligible in homogenates from the rat and extensive in the rabbit; guinea-pig liver homogenates had intermediate ability. Metabolic oxidation of 1-phenyl-2-propanol was negligible in all three species. The amount of deamination of amphetamine and of N-n-propylamphetamine was approximately equal, in vitro, in rats and guinea-pigs but two to three times greater in liver homogenates from rabbits. Approximately three times more deaminated products were formed from the in vitro metabolism of N-n-propylamphetamine than from amphetamine metabolism by all three species.", "contents": "Species differences in the in vitro metabolic reduction of the amphetamine metabolite, 1-phenyl-2-propanone. Marked differences were observed, in the ability of fortified 9000 g liver homogenate supernatants from three species to reduce 1-phenyl-2-propanone to the corresponding alcohol. This metabolic keto-reduction was negligible in homogenates from the rat and extensive in the rabbit; guinea-pig liver homogenates had intermediate ability. Metabolic oxidation of 1-phenyl-2-propanol was negligible in all three species. The amount of deamination of amphetamine and of N-n-propylamphetamine was approximately equal, in vitro, in rats and guinea-pigs but two to three times greater in liver homogenates from rabbits. Approximately three times more deaminated products were formed from the in vitro metabolism of N-n-propylamphetamine than from amphetamine metabolism by all three species."}
{"id": "PMID:27607", "title": "Effectiveness of pyridostigmine in reversing neuromuscular blockade produced by soman.", "content": "The effects of pyridostigmine pretreatment on the neuromuscular blockade produced by soman in anaesthetized, atropinized animals have been studied on the soleus and anterior tibialis muscle (rhesus monkeys, cats and rabbits) and the gastrocnemius muscle (guinea-pigs and rats). Pyridostigmine pretreatment produced a complete recovery of neuromuscular function following blockade by soman; the rate of recovery was similar in all the species, suggesting a common mechanism of action. In the absence of pyridostigmine or if pyridostigmine was delayed until after blockade by soman, there was no recovery of neuromuscular function. Detailed studies in the guinea-pig showed that the recovery of neuromuscular function was related to the dose of soman and to the degree of carbamoylation of blood cholinesterase at the time of nerve agent challenge, i.e. to the dose of pyridostigmine and the time interval between the administration of pyridostigmine and soman. It is suggested that the effectiveness of pyridostigmine pretreatment is due to the carbamoylation of a portion of the tissue acetylcholinesterase, which protects it against irreversible inhibition by soman: after poisoning spontaneous decarbamoylation produces sufficient free acetylcholinesterase to restore normal function.", "contents": "Effectiveness of pyridostigmine in reversing neuromuscular blockade produced by soman. The effects of pyridostigmine pretreatment on the neuromuscular blockade produced by soman in anaesthetized, atropinized animals have been studied on the soleus and anterior tibialis muscle (rhesus monkeys, cats and rabbits) and the gastrocnemius muscle (guinea-pigs and rats). Pyridostigmine pretreatment produced a complete recovery of neuromuscular function following blockade by soman; the rate of recovery was similar in all the species, suggesting a common mechanism of action. In the absence of pyridostigmine or if pyridostigmine was delayed until after blockade by soman, there was no recovery of neuromuscular function. Detailed studies in the guinea-pig showed that the recovery of neuromuscular function was related to the dose of soman and to the degree of carbamoylation of blood cholinesterase at the time of nerve agent challenge, i.e. to the dose of pyridostigmine and the time interval between the administration of pyridostigmine and soman. It is suggested that the effectiveness of pyridostigmine pretreatment is due to the carbamoylation of a portion of the tissue acetylcholinesterase, which protects it against irreversible inhibition by soman: after poisoning spontaneous decarbamoylation produces sufficient free acetylcholinesterase to restore normal function."}
{"id": "PMID:27608", "title": "The relationship between cholinesterase inhibition in the chick biventer cervicis muscle and its sensitivity to exogenous acetylcholine.", "content": "The effect of physostigmine has been studied on cholinesterase in homogenates of chick biventer cervicis muscles and on the contractile responses of the intact muscles to acetylcholine and carbachol. The concentration of physostigmine required to produce the maximum increase in sensitivity to acetylcholine almost completely inhibited the cholinesterase in muscle homogenates. This concentration of physostigmine had no effect on muscle contractures elicited by carbachol. By taking account of the combined effects of acetylcholine diffusion and enzymic hydrolysis, a quantitative theoretical relationship has been derived between the level of cholinesterase activity in cylindrical muscles and the fractional occupancy of the acetylcholine receptors in these muscles in the presence of different concentrations of exogenous acetylcholine. This theory attributes the thousand-fold increase in sensitivity to exogenous acetylcholine produced by anticholinesterases in chick biventer cervicis muscles largely to an alteration in acetylcholine concentration gradient within the muscle and accounts satisfactorily for the shift in the dose-response curve for acetylcholine which occurs after treatment of the muscles with various concentrations of physostigmine.", "contents": "The relationship between cholinesterase inhibition in the chick biventer cervicis muscle and its sensitivity to exogenous acetylcholine. The effect of physostigmine has been studied on cholinesterase in homogenates of chick biventer cervicis muscles and on the contractile responses of the intact muscles to acetylcholine and carbachol. The concentration of physostigmine required to produce the maximum increase in sensitivity to acetylcholine almost completely inhibited the cholinesterase in muscle homogenates. This concentration of physostigmine had no effect on muscle contractures elicited by carbachol. By taking account of the combined effects of acetylcholine diffusion and enzymic hydrolysis, a quantitative theoretical relationship has been derived between the level of cholinesterase activity in cylindrical muscles and the fractional occupancy of the acetylcholine receptors in these muscles in the presence of different concentrations of exogenous acetylcholine. This theory attributes the thousand-fold increase in sensitivity to exogenous acetylcholine produced by anticholinesterases in chick biventer cervicis muscles largely to an alteration in acetylcholine concentration gradient within the muscle and accounts satisfactorily for the shift in the dose-response curve for acetylcholine which occurs after treatment of the muscles with various concentrations of physostigmine."}
{"id": "PMID:27609", "title": "Pharmacological study of chicken airway smooth muscle.", "content": "Isolated chicken bronchus contracts to carbachol, PGF2alpha, histamine, 5-HT, bradykinin and phenylephrine. The bronchial strips from the horse plasma sensitized domestic fowl contracted to specific sensitizing antigen in vitro (Schultz-Dale anaphylactic reaction) and were 5 to 10 fold more reactive to PGF2alpha, histamine and 5-HT compared with the bronchi from normal chickens. Second antigen challenge was inactive or produced a weak response (desensitization). Allowing the bronchi to rest for 1 h resulted in partial recovery of anaphylactic response. Bronchi which had partially contracted submaximally to carbachol, antigen or PGF2alpha, relaxed to isoprenaline, adrenaline and PGE1 and E2.", "contents": "Pharmacological study of chicken airway smooth muscle. Isolated chicken bronchus contracts to carbachol, PGF2alpha, histamine, 5-HT, bradykinin and phenylephrine. The bronchial strips from the horse plasma sensitized domestic fowl contracted to specific sensitizing antigen in vitro (Schultz-Dale anaphylactic reaction) and were 5 to 10 fold more reactive to PGF2alpha, histamine and 5-HT compared with the bronchi from normal chickens. Second antigen challenge was inactive or produced a weak response (desensitization). Allowing the bronchi to rest for 1 h resulted in partial recovery of anaphylactic response. Bronchi which had partially contracted submaximally to carbachol, antigen or PGF2alpha, relaxed to isoprenaline, adrenaline and PGE1 and E2."}
{"id": "PMID:27610", "title": "The evaluation of cardiovascular drugs in the anaesthetized, unrestrained rat.", "content": "A method is reported which allows continuous long-term drug administration and simultaneous blood pressure measurement in the unanaesthetized unrestrained rat. The external jugular vein and abdominal aorta were cannulated and the opposite ends of the cannulae were passed subcutaneously and exteriorized at the back of the head. They were then passed through a spring attached at the lower end to the skull and, at the upper end, to a counter-weighted cantilever. In rats so prepared, infusion of angiotensin amide 200 ng kg-1 min-1 caused a rise of blood pressure which lasted the 48 h infusion period. Heart rate decreased initially but recovered within 6 h. Angiotensin amde 30 ng kg-1 min-1, infused up to seven days, was without effect on blood pressure or heart rate, and both doses of angiotensin amide failed to alter cardiac catecholamine turnover. Hydralazine, mecamylamine and clonidine reduced blood pressure to 63, 62 and 84% of control respectively while clonidine induced a transient increase before its depressor effect. Heart rate was increased by hydralazine to 138%, and decrease by clonidine to 74% of control, and was unaffected by mecamylamine. The magnitude of pressor response to noradrenaline, tyramine and angiotensin was reduced by hydralazine and increased by mecamylamine. Clonidine increased the pressor response to angiotensin but had no effect on that to noradrenaline or tyramine.", "contents": "The evaluation of cardiovascular drugs in the anaesthetized, unrestrained rat. A method is reported which allows continuous long-term drug administration and simultaneous blood pressure measurement in the unanaesthetized unrestrained rat. The external jugular vein and abdominal aorta were cannulated and the opposite ends of the cannulae were passed subcutaneously and exteriorized at the back of the head. They were then passed through a spring attached at the lower end to the skull and, at the upper end, to a counter-weighted cantilever. In rats so prepared, infusion of angiotensin amide 200 ng kg-1 min-1 caused a rise of blood pressure which lasted the 48 h infusion period. Heart rate decreased initially but recovered within 6 h. Angiotensin amde 30 ng kg-1 min-1, infused up to seven days, was without effect on blood pressure or heart rate, and both doses of angiotensin amide failed to alter cardiac catecholamine turnover. Hydralazine, mecamylamine and clonidine reduced blood pressure to 63, 62 and 84% of control respectively while clonidine induced a transient increase before its depressor effect. Heart rate was increased by hydralazine to 138%, and decrease by clonidine to 74% of control, and was unaffected by mecamylamine. The magnitude of pressor response to noradrenaline, tyramine and angiotensin was reduced by hydralazine and increased by mecamylamine. Clonidine increased the pressor response to angiotensin but had no effect on that to noradrenaline or tyramine."}
{"id": "PMID:27624", "title": "Physicochemical properties of amphoteric beta-lactam antibiotics I: Stability, solubility, and dissolution behavior of amino penicillins as a function of pH.", "content": "The degradation rate, solubility, and dissolution rate of amino penicillins, amoxicillin, ampicillin, epicillin, and cyclacillin, were determined quantitatively as a function of pH. In the pH range studied, 0.30-10.50, the degradation of amoxicillin and epicillin followed pseudo-first-order kinetics to give the same type of pH-rate profiles as those of ampicillin and cyclacillin. Cyclacillin anhydrate was the most soluble, followed in order by ampicillin anhydrate, ampicillin trihydrate, amoxicillin trihydrate, and epicillin anhydrate. These pH-solubility profiles showed showed U-shaped curves. The dissolution rate constants from the rotating disk were analyzed by the simultaneous chemical reaction and diffusion models. Their relative bioavailability after a single oral administration was assessed from their physicochemical properties determined in vitro.", "contents": "Physicochemical properties of amphoteric beta-lactam antibiotics I: Stability, solubility, and dissolution behavior of amino penicillins as a function of pH. The degradation rate, solubility, and dissolution rate of amino penicillins, amoxicillin, ampicillin, epicillin, and cyclacillin, were determined quantitatively as a function of pH. In the pH range studied, 0.30-10.50, the degradation of amoxicillin and epicillin followed pseudo-first-order kinetics to give the same type of pH-rate profiles as those of ampicillin and cyclacillin. Cyclacillin anhydrate was the most soluble, followed in order by ampicillin anhydrate, ampicillin trihydrate, amoxicillin trihydrate, and epicillin anhydrate. These pH-solubility profiles showed showed U-shaped curves. The dissolution rate constants from the rotating disk were analyzed by the simultaneous chemical reaction and diffusion models. Their relative bioavailability after a single oral administration was assessed from their physicochemical properties determined in vitro."}
{"id": "PMID:27625", "title": "Mechanism of adsorption of clindamycin and tetracycline by montmorillonite.", "content": "IR and X-ray analyses of the interaction of clindamycin with montmorillonite indicate that clindamycin is adsorbed by a cation-exchange mechanism under pH conditions favoring the cationic form of the drug and by physical adsorption when the unionized drug is present. This physical adsorption is relatively weak since the drug is readily desorbed by alkaline washing. Tetracycline is adsorbed by cation exchange at low pH values where the +00 species predominates. Complexation with divalent interlayer cations contributes significantly to adsorption at higher pH values where the +-0 and +-- species exist. In a strongly alkaline solution, the 0-- species was not adsorbed in the interlayer space of montmorillonite but rather produced an external calcium-tetracycline complex. This study illustrates the utility of X-ray and IR analyses in elucidating the mechanisms responsible for clay-drug interactions.", "contents": "Mechanism of adsorption of clindamycin and tetracycline by montmorillonite. IR and X-ray analyses of the interaction of clindamycin with montmorillonite indicate that clindamycin is adsorbed by a cation-exchange mechanism under pH conditions favoring the cationic form of the drug and by physical adsorption when the unionized drug is present. This physical adsorption is relatively weak since the drug is readily desorbed by alkaline washing. Tetracycline is adsorbed by cation exchange at low pH values where the +00 species predominates. Complexation with divalent interlayer cations contributes significantly to adsorption at higher pH values where the +-0 and +-- species exist. In a strongly alkaline solution, the 0-- species was not adsorbed in the interlayer space of montmorillonite but rather produced an external calcium-tetracycline complex. This study illustrates the utility of X-ray and IR analyses in elucidating the mechanisms responsible for clay-drug interactions."}
{"id": "PMID:27627", "title": "Oxidative degradation of pharmaceutically important phenothiazines III: Kinetics and mechanism of promethazine oxidation.", "content": "The kinetics of the thermal degradation of promethazine in an acidic medium under various conditions were investigated. The degradation of promethazine and the formation of some degradation products were studied under aerobic and anaerobic conditions. The influence of pH, metal ions such as copper(II) and iron (III), and antioxidants was investigated. In an oxygen-saturated medium, promethazine generally followed first-order kinetics. Increasing the pH increased the degradation rate to a limiting value at pH 5. Addition copper (II) increased the degradation rate over the whole process, while iron (III) caused an increase for only a short time. Ascorbic acid sometimes increased the degradation rate, while higher concentrations of hydroquinone also accelerated the degradation. Pyrosulfite did not have any influence. Under anaerobic conditions, promethazine degraded only in the presence of copper (II) and iorn (III) ions. As a result of the studies on the qualitative and quantitative aspects of the oxidation process, a mechanism for the oxidative degradation of promethazine is suggested. Promethazine 5-oxide and a number of degradation products without intact side chains are formed via a semiquinone free radical. The influence of several factors on the degradation process is discussed.", "contents": "Oxidative degradation of pharmaceutically important phenothiazines III: Kinetics and mechanism of promethazine oxidation. The kinetics of the thermal degradation of promethazine in an acidic medium under various conditions were investigated. The degradation of promethazine and the formation of some degradation products were studied under aerobic and anaerobic conditions. The influence of pH, metal ions such as copper(II) and iron (III), and antioxidants was investigated. In an oxygen-saturated medium, promethazine generally followed first-order kinetics. Increasing the pH increased the degradation rate to a limiting value at pH 5. Addition copper (II) increased the degradation rate over the whole process, while iron (III) caused an increase for only a short time. Ascorbic acid sometimes increased the degradation rate, while higher concentrations of hydroquinone also accelerated the degradation. Pyrosulfite did not have any influence. Under anaerobic conditions, promethazine degraded only in the presence of copper (II) and iorn (III) ions. As a result of the studies on the qualitative and quantitative aspects of the oxidation process, a mechanism for the oxidative degradation of promethazine is suggested. Promethazine 5-oxide and a number of degradation products without intact side chains are formed via a semiquinone free radical. The influence of several factors on the degradation process is discussed."}
{"id": "PMID:27628", "title": "Nature of amorphous aluminum hydroxycarbonate.", "content": "The titration of sodium carbonate with aluminum nitrate is shown to produce amorphous aluminum hydroxycarbonate. This compound is not stoichiometric, although the maximum carbonate to aluminum ratio appears to be 0.5. The pH conditions for achieving the maximum carbonate content are concentration dependent. A model for the particle surface at the solution interface is proposed. This model accounts for the presence of carbonate directly coordinated to the aluminum and carbonate adsorbed by electrostatic forces. Sodium is present in the diffuse layer and is, therefore, not an integral part of the structure.", "contents": "Nature of amorphous aluminum hydroxycarbonate. The titration of sodium carbonate with aluminum nitrate is shown to produce amorphous aluminum hydroxycarbonate. This compound is not stoichiometric, although the maximum carbonate to aluminum ratio appears to be 0.5. The pH conditions for achieving the maximum carbonate content are concentration dependent. A model for the particle surface at the solution interface is proposed. This model accounts for the presence of carbonate directly coordinated to the aluminum and carbonate adsorbed by electrostatic forces. Sodium is present in the diffuse layer and is, therefore, not an integral part of the structure."}
{"id": "PMID:27629", "title": "Interference in assays for hydralazine in humans by a major plasma metabolite, hydralazine pyruvic acid hydrazone.", "content": "The present study showed that published spectrophotometric and GLC methods for hydralazine in plasma do not distinguish between the drug and a major plasma metabolite, hydralazine pyruvic acid hydrazone. These methods involve the acid treatment of the sample, which hydrolyzes that hydrazone back to hydralazine. A specific GLC assay for the hydrazone was developed and involves its selective extraction from plasma and transformation to 3-trifluoromethyl-s-triazolo[3,4-a]phthalazine. This derivative could be sensitively measured by GLC using an electron-capture detector. With this procedure, it was shown that most \"apparent hydralazine\" in plasma is the hydrazone, which forms rapidly from hydralazine and endogenous pyruvic acid. Previous work indicated that the hydrazone was inactive when administered intravenously to rabbits.", "contents": "Interference in assays for hydralazine in humans by a major plasma metabolite, hydralazine pyruvic acid hydrazone. The present study showed that published spectrophotometric and GLC methods for hydralazine in plasma do not distinguish between the drug and a major plasma metabolite, hydralazine pyruvic acid hydrazone. These methods involve the acid treatment of the sample, which hydrolyzes that hydrazone back to hydralazine. A specific GLC assay for the hydrazone was developed and involves its selective extraction from plasma and transformation to 3-trifluoromethyl-s-triazolo[3,4-a]phthalazine. This derivative could be sensitively measured by GLC using an electron-capture detector. With this procedure, it was shown that most \"apparent hydralazine\" in plasma is the hydrazone, which forms rapidly from hydralazine and endogenous pyruvic acid. Previous work indicated that the hydrazone was inactive when administered intravenously to rabbits."}
{"id": "PMID:27630", "title": "Automated potentiometric procedure for studying dissolution kinetics acidic drugs under sink conditions.", "content": "An automated potentiometric procedure was used for studying in vitro dissolution kinetics of acidic drugs. Theoretical considerations indicated that the pH-stat method could be used to establish approximate sink conditions or, possibly, a perfect sink. Data obtained from dissolution studies using the pH-stat method were compared with data obtained from known sink and nonsink conditions. These comparisons indicated that the pH-stat method can be used to establish a sink condition for dissolution studies. The effective diffusion layer thicknesses for benzoic and salicylic acids dissolving in water were determined, and a theoretical dissolution rate was calculated utilizing these values. The close agreement between the experimental dissolution rates obtained under pH-stat conditions and theoretical dissolution rates indicated that perfect sink conditions were established under the experimental conditions used.", "contents": "Automated potentiometric procedure for studying dissolution kinetics acidic drugs under sink conditions. An automated potentiometric procedure was used for studying in vitro dissolution kinetics of acidic drugs. Theoretical considerations indicated that the pH-stat method could be used to establish approximate sink conditions or, possibly, a perfect sink. Data obtained from dissolution studies using the pH-stat method were compared with data obtained from known sink and nonsink conditions. These comparisons indicated that the pH-stat method can be used to establish a sink condition for dissolution studies. The effective diffusion layer thicknesses for benzoic and salicylic acids dissolving in water were determined, and a theoretical dissolution rate was calculated utilizing these values. The close agreement between the experimental dissolution rates obtained under pH-stat conditions and theoretical dissolution rates indicated that perfect sink conditions were established under the experimental conditions used."}
{"id": "PMID:27633", "title": "A controlled trial of antiemetics in abortion by PGF2alpha and laminaria.", "content": "Women undergoing abortion by intraamniotic prostaglandin F2alpha were randomized to receive either prochlorperazine edisylate 10mg, hydroxyzine hydrochloride 100mg, or a placebo every four hours by intramuscular injection in a double-blind fashion. Vomiting was significantly more frequent in the placebo-treated group [0.2 +/- 1.5 SD episodes per patient, n=21]  than in the groups treated with prochlorperazine [1.2 +/- 0.5 episodes per patient, n=21] or hydroxyzine [0.3 +/- 0.8 episodes per patient, n=19]. The mean number of merperidine injections in the antiemetic-treated groups was lower than in the control group, but this effect was not statistically significant. There was no significant difference between the treated and the control groups in the interval from prostaglandin treatment to abortion.", "contents": "A controlled trial of antiemetics in abortion by PGF2alpha and laminaria. Women undergoing abortion by intraamniotic prostaglandin F2alpha were randomized to receive either prochlorperazine edisylate 10mg, hydroxyzine hydrochloride 100mg, or a placebo every four hours by intramuscular injection in a double-blind fashion. Vomiting was significantly more frequent in the placebo-treated group [0.2 +/- 1.5 SD episodes per patient, n=21]  than in the groups treated with prochlorperazine [1.2 +/- 0.5 episodes per patient, n=21] or hydroxyzine [0.3 +/- 0.8 episodes per patient, n=19]. The mean number of merperidine injections in the antiemetic-treated groups was lower than in the control group, but this effect was not statistically significant. There was no significant difference between the treated and the control groups in the interval from prostaglandin treatment to abortion."}
{"id": "PMID:27634", "title": "Novel anxiolytic agents derived from alpha-amino-alpha-phenyl-o-tolyl-4H-triazoles and -imidazoles.", "content": "Several new alpha-amino-alpha-phenyl-o-tolytriazoles and -imidazoles have been prepared in one step by means of a novel reductive rearrangement of the corresponding benzodiazepines with hydrazine hydrate. These new triazoles were found to have moderate sedative and muscle relaxing activity in mice (i.e., these compounds depressed the traction and dish reflexes at higher doses than did diazepam) but were very potent antagonists of the clonic convulsions induced in mice by the administration of pentylenetetrazole. Furthermore, they antagonized the lethality induced by thiosemicarbazide. While these new compounds were very active in mice, most were inactive in rats. These results are discussed with reference to the metabolism of compound 13.", "contents": "Novel anxiolytic agents derived from alpha-amino-alpha-phenyl-o-tolyl-4H-triazoles and -imidazoles. Several new alpha-amino-alpha-phenyl-o-tolytriazoles and -imidazoles have been prepared in one step by means of a novel reductive rearrangement of the corresponding benzodiazepines with hydrazine hydrate. These new triazoles were found to have moderate sedative and muscle relaxing activity in mice (i.e., these compounds depressed the traction and dish reflexes at higher doses than did diazepam) but were very potent antagonists of the clonic convulsions induced in mice by the administration of pentylenetetrazole. Furthermore, they antagonized the lethality induced by thiosemicarbazide. While these new compounds were very active in mice, most were inactive in rats. These results are discussed with reference to the metabolism of compound 13."}
{"id": "PMID:27635", "title": "Synthesis of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen, and its phenolic sulfate conjugate.", "content": "The synthesis of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 4), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 3), and its phenolic sulfate conjugate (potassium N-acetyl-N-hydroxy-p-aminophenyl sulfate) (13) is described. Potassium p-nitrophenyl sulfate was reduced to the hydroxylamine, acetylated, and treated with sulfatase to yield N-hydroxyacetaminophen. The structures assigned are supported by the spectral data (IR, UV, MS, 1H NMR, and 13C NMR). N-Hydroxyacetaminophen was found to be moderately unstable at physiological pH and temperature, whereas it phenolic sulfate conjugate was stable.", "contents": "Synthesis of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen, and its phenolic sulfate conjugate. The synthesis of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 4), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 3), and its phenolic sulfate conjugate (potassium N-acetyl-N-hydroxy-p-aminophenyl sulfate) (13) is described. Potassium p-nitrophenyl sulfate was reduced to the hydroxylamine, acetylated, and treated with sulfatase to yield N-hydroxyacetaminophen. The structures assigned are supported by the spectral data (IR, UV, MS, 1H NMR, and 13C NMR). N-Hydroxyacetaminophen was found to be moderately unstable at physiological pH and temperature, whereas it phenolic sulfate conjugate was stable."}
{"id": "PMID:27637", "title": "Neuroleptics related to butaclamol. Synthesis and some psychopharmacological effects of a series of 3-aryl analogues.", "content": "The synthesis and some pharmacological effects of 16 3-aryl analogues of butaclamol, a new antipsychotic drug, are described. The animal models were predictive of neuroleptic activity as well as side effects commonly associated with neuroleptic therapy. The results indicate that the 3-substituent plays a critical role with regard to the potency of the compounds as well as to their tendencies to induce extrapyramidal side effects and/or hypotension.", "contents": "Neuroleptics related to butaclamol. Synthesis and some psychopharmacological effects of a series of 3-aryl analogues. The synthesis and some pharmacological effects of 16 3-aryl analogues of butaclamol, a new antipsychotic drug, are described. The animal models were predictive of neuroleptic activity as well as side effects commonly associated with neuroleptic therapy. The results indicate that the 3-substituent plays a critical role with regard to the potency of the compounds as well as to their tendencies to induce extrapyramidal side effects and/or hypotension."}
{"id": "PMID:27638", "title": "5-Carboxamido-4-amino-3-isoxazolidone, and asparagine analogue.", "content": "trans-Aziridine-2,3-dicarboxylic ester was used to prepare the required beta-chlorohydroxamic acid used in the synthesis of the title compound. The trans configuration of the asparagine analogue was established by hydrogenolysis to erythro-beta-hydroxyasparagine amide. Neither the title compound nor the intermediate aziridinehydroxamic acid (8) showed significant activity against the L1210 and P-388 tumors. The title compound was inactive as an inhibitor of asparagine synthetase from Novikoff hepatoma and did not inhibit the growth of some 25 bacteria and fungi.", "contents": "5-Carboxamido-4-amino-3-isoxazolidone, and asparagine analogue. trans-Aziridine-2,3-dicarboxylic ester was used to prepare the required beta-chlorohydroxamic acid used in the synthesis of the title compound. The trans configuration of the asparagine analogue was established by hydrogenolysis to erythro-beta-hydroxyasparagine amide. Neither the title compound nor the intermediate aziridinehydroxamic acid (8) showed significant activity against the L1210 and P-388 tumors. The title compound was inactive as an inhibitor of asparagine synthetase from Novikoff hepatoma and did not inhibit the growth of some 25 bacteria and fungi."}
{"id": "PMID:27639", "title": "Autosomal recessive postaxial polydactyly type A in a Sicilian family.", "content": "Postaxial polydactyly type A was present in several members of a Sicilian family. The anomaly was probably transmitted as an autosomal recessive character. Two polydactylous subjects were also beta-thalassaemia carriers, but a linkage between the two mutant genes could be excluded. Two patients with hexadactyly had a fifth digital triradius.", "contents": "Autosomal recessive postaxial polydactyly type A in a Sicilian family. Postaxial polydactyly type A was present in several members of a Sicilian family. The anomaly was probably transmitted as an autosomal recessive character. Two polydactylous subjects were also beta-thalassaemia carriers, but a linkage between the two mutant genes could be excluded. Two patients with hexadactyly had a fifth digital triradius."}
{"id": "PMID:27641", "title": "The influence of various cations on the catalytic properties of clays.", "content": "Polymerization of alanine adenylate in the presence of various clays in their Na form gave increasing degrees of polymerization in the following order: montmorillonite less than nontronite less than hectorite. With montmorillonite, presaturated with different cations the order was: Mg less Ca less than Fe less than Al less than Na. From all these clays, hectorite was the only one to enable also some polymerization of lysine.", "contents": "The influence of various cations on the catalytic properties of clays. Polymerization of alanine adenylate in the presence of various clays in their Na form gave increasing degrees of polymerization in the following order: montmorillonite less than nontronite less than hectorite. With montmorillonite, presaturated with different cations the order was: Mg less Ca less than Fe less than Al less than Na. From all these clays, hectorite was the only one to enable also some polymerization of lysine."}
{"id": "PMID:27642", "title": "Biotin. Its place in evolution.", "content": "In the previous article we try to give an explanation for the success of models of enzymatic reactions in which coenzymes play a role. However, one vital cofactor that has thus far not yielded appreciably to this approach is biotin. We attempt to show that biotin presents a fundamentally new sort of problem to bioorganic chemistry; this problem requires consideration both of the origin of life and subsequent evolution in any attempt to understand the anomalies offered by this cofactor.", "contents": "Biotin. Its place in evolution. In the previous article we try to give an explanation for the success of models of enzymatic reactions in which coenzymes play a role. However, one vital cofactor that has thus far not yielded appreciably to this approach is biotin. We attempt to show that biotin presents a fundamentally new sort of problem to bioorganic chemistry; this problem requires consideration both of the origin of life and subsequent evolution in any attempt to understand the anomalies offered by this cofactor."}
{"id": "PMID:27644", "title": "Covalent coupling of calf brain prolidase.", "content": "Calf brain prolidase covalently bound to CNBr-Sepharose 4B, retained about 32% of the activity of the uncoupled enzyme. The free enzyme showed slightly greater stability than the bound preparation when stored at 20 degrees C or at 0 degrees C. However, in either case the free and bound enzymes were more stable at the lower temperature. Greater thermal stability was shown by the free enzyme than by the bound preparation over a temperature range of 25 degrees C-60 degrees C. The free and bound prolidase, with and without Mn+2, had maximal activity at pH 4.0. Although the bound enzyme showed a single maximum, the free preparation exhibited three pH maxima of 4.0, 9.0, and 6.5, in decreasing order of activity. The ions Ag+, Cu+, Hg+2, and Zn+2 were strongly inhibitory on the free enzyme, whereas inhibition of the bound enzyme, with the exception of Zn+2 , was less. Unlike the coupled enzyme, a stimulatory effect was obtained on the free preparation with Co+3, Mg+2, and Mn+2. Various other compounds were studied and their effects were noted.", "contents": "Covalent coupling of calf brain prolidase. Calf brain prolidase covalently bound to CNBr-Sepharose 4B, retained about 32% of the activity of the uncoupled enzyme. The free enzyme showed slightly greater stability than the bound preparation when stored at 20 degrees C or at 0 degrees C. However, in either case the free and bound enzymes were more stable at the lower temperature. Greater thermal stability was shown by the free enzyme than by the bound preparation over a temperature range of 25 degrees C-60 degrees C. The free and bound prolidase, with and without Mn+2, had maximal activity at pH 4.0. Although the bound enzyme showed a single maximum, the free preparation exhibited three pH maxima of 4.0, 9.0, and 6.5, in decreasing order of activity. The ions Ag+, Cu+, Hg+2, and Zn+2 were strongly inhibitory on the free enzyme, whereas inhibition of the bound enzyme, with the exception of Zn+2 , was less. Unlike the coupled enzyme, a stimulatory effect was obtained on the free preparation with Co+3, Mg+2, and Mn+2. Various other compounds were studied and their effects were noted."}
{"id": "PMID:27645", "title": "Characterization of an alkaline protease associated with a granulosis virus of Plodia interpunctella.", "content": "An alkaline protease was found to be associated with the granulosis virus of the Indian meal moth. Plodia interpunctella. The protease was located within the protein matrix of the occluded virus and hydrolyzed the major constituent of this matrix, a 28,000-dalton protein (granulin), to a mixture of polypeptides ranging in molecular weight from 10,000 to 27,000. A rapid, sensitive assay for the protease was developed using radioactively labeled granulosis virus as substrate. With this assay, the proteolytic activity could be detected by measuring the release of acid-soluble peptides from the labeled virus. The protease had a pH optimum of 10.5 and a temperature optimum of 40 degrees C and was inhibited by diisopropyl phosphorofluoridate, phenylmethylsulfonyl fluoride, and L-(1-tosylamido-2-phenyl) ethyl chloromethyl ketone. Purification of the protease from matrix protein was achieved by anion-exchange and gel permeation chromatography. The molecular weight of the isolated protease, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, was approximately 14,000.", "contents": "Characterization of an alkaline protease associated with a granulosis virus of Plodia interpunctella. An alkaline protease was found to be associated with the granulosis virus of the Indian meal moth. Plodia interpunctella. The protease was located within the protein matrix of the occluded virus and hydrolyzed the major constituent of this matrix, a 28,000-dalton protein (granulin), to a mixture of polypeptides ranging in molecular weight from 10,000 to 27,000. A rapid, sensitive assay for the protease was developed using radioactively labeled granulosis virus as substrate. With this assay, the proteolytic activity could be detected by measuring the release of acid-soluble peptides from the labeled virus. The protease had a pH optimum of 10.5 and a temperature optimum of 40 degrees C and was inhibited by diisopropyl phosphorofluoridate, phenylmethylsulfonyl fluoride, and L-(1-tosylamido-2-phenyl) ethyl chloromethyl ketone. Purification of the protease from matrix protein was achieved by anion-exchange and gel permeation chromatography. The molecular weight of the isolated protease, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, was approximately 14,000."}
{"id": "PMID:27646", "title": "The urologic manifestations of XO/XY mosaicism.", "content": "The mosaic karyotype XO/XY is expressed by a spectrum of genital phenotypes, ranging from normal male through ambiguous genitalia to normal female. The urologist may see some of these patients because of the following clinical presentations: 1) ambiguous genitalia with a chromatin-negative buccal smear, 2) hypospadias with cryptorchidism or 3) cryptorchidism with m\u00fcllerian remnants, discovered unexpectedly during inguinal operations. Reliable karyotyping is mandatory for diagnosis of XO/XY patients. Management should include laparotomy with excision of any intra-abdominal gonads (testis and/or streak gonad) because these are prone to develop malignancies that may occur before puberty. Female sex assignment and a reconstructive operation are advised in cases with severely deficient virilization of the genitalia.", "contents": "The urologic manifestations of XO/XY mosaicism. The mosaic karyotype XO/XY is expressed by a spectrum of genital phenotypes, ranging from normal male through ambiguous genitalia to normal female. The urologist may see some of these patients because of the following clinical presentations: 1) ambiguous genitalia with a chromatin-negative buccal smear, 2) hypospadias with cryptorchidism or 3) cryptorchidism with m\u00fcllerian remnants, discovered unexpectedly during inguinal operations. Reliable karyotyping is mandatory for diagnosis of XO/XY patients. Management should include laparotomy with excision of any intra-abdominal gonads (testis and/or streak gonad) because these are prone to develop malignancies that may occur before puberty. Female sex assignment and a reconstructive operation are advised in cases with severely deficient virilization of the genitalia."}
{"id": "PMID:27648", "title": "Bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, left cryptorchidism and angioma of the bladder.", "content": "The first case of bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, a left undescended testicle and angioma of the bladder is reported. Bilateral ureteroneocystostomy and left orchiopexy were done. The patient is well 3 months postoperatively with no urinary tract infection and stable renal function.", "contents": "Bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, left cryptorchidism and angioma of the bladder. The first case of bilateral trifid ureters associated with fused kidney, ureterovesical stenosis, a left undescended testicle and angioma of the bladder is reported. Bilateral ureteroneocystostomy and left orchiopexy were done. The patient is well 3 months postoperatively with no urinary tract infection and stable renal function."}
{"id": "PMID:27659", "title": "[The determination of a small amount of chlorine in the atmosphere by using 4-nitroaniline (author's transl)].", "content": "The determination of small amount of chlorine in the atmosphere is carried on ordinarily by omicron-toluidine method at present. However, this method is not recommended because the issued colour is unstable and omicron-toluidine itself belongs in the first group member of the Ordinance on Prevention of Particular Chemical Hazards Substances. Authors recommend 4-nitroaniline method, reported by J. Gabbay etc., because this method is stable and more practical. Although the colour that issued from the reaction of chlorine with 4-nitroaniline is affected by the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed by introducing the sample gas into the layer of H2SO4-52Cr2O7 mixture immersed in glassfiber filter for micro-analysis. In this paper, influence of pH of the issued colour, stability, stream velocity of samplegas and effect of reducing substance are discussed.", "contents": "[The determination of a small amount of chlorine in the atmosphere by using 4-nitroaniline (author's transl)]. The determination of small amount of chlorine in the atmosphere is carried on ordinarily by omicron-toluidine method at present. However, this method is not recommended because the issued colour is unstable and omicron-toluidine itself belongs in the first group member of the Ordinance on Prevention of Particular Chemical Hazards Substances. Authors recommend 4-nitroaniline method, reported by J. Gabbay etc., because this method is stable and more practical. Although the colour that issued from the reaction of chlorine with 4-nitroaniline is affected by the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed the co-existence of reducing gas, e.g. SO2, H2S or organic gas, but this effect may be removed by introducing the sample gas into the layer of H2SO4-52Cr2O7 mixture immersed in glassfiber filter for micro-analysis. In this paper, influence of pH of the issued colour, stability, stream velocity of samplegas and effect of reducing substance are discussed."}
{"id": "PMID:27664", "title": "[Effect of adrenergic beta receptor blockaders on bronchial patency in ischemic heart disease].", "content": "The effect of beta-adrenergic blocking agents inderal, trazicor, visken, benzoral and aptin on the bronchial patency was studied by means of four ventilation indices in 85 patients, 62 of whome had various diseases of the lungs; 44 of these patients had bronchial obstruction. It was established that all beta-blocking agents are detrimental to bronchial patency in patients with concomitant bronchial obstruction. In exacerbation of bronchial asthma, beta-blocking agents are contraindictaed. When it is necessary to prescribe beta-blocking agents for other patients with concomitant bronchial obstruction visken is the drug of choice. It should be given per os, with preliminary control of the function of external respiration.", "contents": "[Effect of adrenergic beta receptor blockaders on bronchial patency in ischemic heart disease]. The effect of beta-adrenergic blocking agents inderal, trazicor, visken, benzoral and aptin on the bronchial patency was studied by means of four ventilation indices in 85 patients, 62 of whome had various diseases of the lungs; 44 of these patients had bronchial obstruction. It was established that all beta-blocking agents are detrimental to bronchial patency in patients with concomitant bronchial obstruction. In exacerbation of bronchial asthma, beta-blocking agents are contraindictaed. When it is necessary to prescribe beta-blocking agents for other patients with concomitant bronchial obstruction visken is the drug of choice. It should be given per os, with preliminary control of the function of external respiration."}
{"id": "PMID:27665", "title": "[Transient myopia with angle closure glaucoma. Case report and biometric findings (author's transl)].", "content": "A 36-year-old man suffered from diarrhoea for some weeks and was treated with Salazosulphapyridie and Fluocortulon when he developed a transient myopia combined with an angle closure glaucoma. The refraction of his mild hyperopic eyes (+0,5 dpt) changed to -5,5 dpt and the intraocular pressure increased to 40 mm Hg in the right and 42 mm Hg in the left eye. Accommodation and pupillary reflexes were normal. Ultrasonic examination showed an increased axial diameter and a forward shifting of the lens. The resulting flattening of the anterior chamber induced the angle closure glaucoma. All symptoms disappeared within a week after the administration of Fluocortulon had been discontinued.", "contents": "[Transient myopia with angle closure glaucoma. Case report and biometric findings (author's transl)]. A 36-year-old man suffered from diarrhoea for some weeks and was treated with Salazosulphapyridie and Fluocortulon when he developed a transient myopia combined with an angle closure glaucoma. The refraction of his mild hyperopic eyes (+0,5 dpt) changed to -5,5 dpt and the intraocular pressure increased to 40 mm Hg in the right and 42 mm Hg in the left eye. Accommodation and pupillary reflexes were normal. Ultrasonic examination showed an increased axial diameter and a forward shifting of the lens. The resulting flattening of the anterior chamber induced the angle closure glaucoma. All symptoms disappeared within a week after the administration of Fluocortulon had been discontinued."}
{"id": "PMID:27691", "title": "Semisynthetic derivatives of pyrrolizidine alkaloids of pharmacodynamic importance: a review.", "content": "Pyrrolizidine alkaloids occur in more than 40 genera. Among these are two important genera, Senecio and Crotalaria, which have been responsible for heavy losses of livestock and poisoning in man due to their hepatotoxicity. Pyrrolizidine alkaloids are also reported to possess a number of other biological activities. Attempts have been made to convert the pyrrolizidine alkaloids to new structures by synthetic modifications. One hundred and twenty semisynthetic compounds were developed and investigated pharmacologically. The range of activity exhibited was hypotensive, local anesthetic, ganglion blocking, neuromuscular blocking and antispasmodic. The five most promising compounds of these series were subjected to detailed pharmacological investigations.", "contents": "Semisynthetic derivatives of pyrrolizidine alkaloids of pharmacodynamic importance: a review. Pyrrolizidine alkaloids occur in more than 40 genera. Among these are two important genera, Senecio and Crotalaria, which have been responsible for heavy losses of livestock and poisoning in man due to their hepatotoxicity. Pyrrolizidine alkaloids are also reported to possess a number of other biological activities. Attempts have been made to convert the pyrrolizidine alkaloids to new structures by synthetic modifications. One hundred and twenty semisynthetic compounds were developed and investigated pharmacologically. The range of activity exhibited was hypotensive, local anesthetic, ganglion blocking, neuromuscular blocking and antispasmodic. The five most promising compounds of these series were subjected to detailed pharmacological investigations."}
{"id": "PMID:27696", "title": "An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics.", "content": "Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells.", "contents": "An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics. Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells."}
{"id": "PMID:27701", "title": "Kinetic properties of pyruvate kinase of Neurospora crassa at physiological pH.", "content": "The kinetic properties of pyruvate kinase (EC 2.7.1.40) extracted from the mycelia of Neurospora crassa were examined at physiological pH to determine the role of the enzyme in the regulation of glycolysis. The velocity curve with the substrates, phosphoenolpyruvate and adenosine diphosphate, are hyperbolic. The effect of magnesium, potassium, or calcium on the enzyme is influenced by the pH but not to the extent that would change their role as cofactor or inhibitor. Adenosine triphosphate and citrate remain strong inhibitors even with changes in pH. Fructose-1,6-diphosphate and glucose-6-phosphate are the dual positive effectors at physiological pH. Valine is the only amino acid that inhibits the enzyme at a concentration range of valine found in the mycelial juice. Thus, the properties of the enzyme at physiological pH are significantly different from those observed at neutral pH of the usual assay conditions, but its role as a key regulator of glycolysis is unchanged.", "contents": "Kinetic properties of pyruvate kinase of Neurospora crassa at physiological pH. The kinetic properties of pyruvate kinase (EC 2.7.1.40) extracted from the mycelia of Neurospora crassa were examined at physiological pH to determine the role of the enzyme in the regulation of glycolysis. The velocity curve with the substrates, phosphoenolpyruvate and adenosine diphosphate, are hyperbolic. The effect of magnesium, potassium, or calcium on the enzyme is influenced by the pH but not to the extent that would change their role as cofactor or inhibitor. Adenosine triphosphate and citrate remain strong inhibitors even with changes in pH. Fructose-1,6-diphosphate and glucose-6-phosphate are the dual positive effectors at physiological pH. Valine is the only amino acid that inhibits the enzyme at a concentration range of valine found in the mycelial juice. Thus, the properties of the enzyme at physiological pH are significantly different from those observed at neutral pH of the usual assay conditions, but its role as a key regulator of glycolysis is unchanged."}
{"id": "PMID:27702", "title": "The influence of pH on the growth rate and viability of neutrophilic and acidophilic streptomycetes.", "content": "The influence of pH on the specific growth rates of two acidophilic and two neutrophilic soil streptomycetes was studied. The acidophiles had maximum growth rates over a broad range from pH 4.5 to 5.5, while the neutrophiles had clearly defined optima at pH 7.0. Mycelium of neutrophiles was less tolerant of acidity than that of acidophiles; both showed decreased viability at pH levels below those which allowed growth. Spores of neutrophiles and acidophiles were equally tolerant of acidity and this may allow the former to survive in acid soils. Both spores and mycelium of acidophiles remained viable at pH levels above those allowing growth.", "contents": "The influence of pH on the growth rate and viability of neutrophilic and acidophilic streptomycetes. The influence of pH on the specific growth rates of two acidophilic and two neutrophilic soil streptomycetes was studied. The acidophiles had maximum growth rates over a broad range from pH 4.5 to 5.5, while the neutrophiles had clearly defined optima at pH 7.0. Mycelium of neutrophiles was less tolerant of acidity than that of acidophiles; both showed decreased viability at pH levels below those which allowed growth. Spores of neutrophiles and acidophiles were equally tolerant of acidity and this may allow the former to survive in acid soils. Both spores and mycelium of acidophiles remained viable at pH levels above those allowing growth."}
{"id": "PMID:27703", "title": "Cell wall autolysis in log phase cells of Micrococcus lysodeikticus (luteus).", "content": "Log phase cells of Micrococcus lysodeikticus (luteus) IFO 3333 autolyzed when incubated at 37 C in 0.01 M sodium-phosphate buffer pH 7.5. The enzyme involved in the autolysis was recovered mainly in an aqueous phase from cytoplasmic membranes and cytoplasmic materials treated with n-butanol, and proved to be an N-acetylmuramyl-L-alanine amidase. The autolysis of log phase cells suspended in autolyzing buffer was depressed by the addition of trypsin to the buffer.", "contents": "Cell wall autolysis in log phase cells of Micrococcus lysodeikticus (luteus). Log phase cells of Micrococcus lysodeikticus (luteus) IFO 3333 autolyzed when incubated at 37 C in 0.01 M sodium-phosphate buffer pH 7.5. The enzyme involved in the autolysis was recovered mainly in an aqueous phase from cytoplasmic membranes and cytoplasmic materials treated with n-butanol, and proved to be an N-acetylmuramyl-L-alanine amidase. The autolysis of log phase cells suspended in autolyzing buffer was depressed by the addition of trypsin to the buffer."}
{"id": "PMID:27704", "title": "A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats.", "content": "A method for quantitative extraction of extravasated dye from the skin was studied in guinea pigs and rats. A simple method with a low cost and good recovery was established as follows; A piece of the skin containing extravasated dye was soaked overnight in a stoppered glass tube containing 1 ml of 1 N KOH at 37 C. Then, 9 ml of mixed solution of 0.6 N H3PO4 and acetone (5:13) was added to the tube. The tube was shaken vigorously for a few seconds and centrifuged at 3,000 rpm for 15 min. Absorbance of supernatant was measured at 620 nm. The recovery rate of the dye was about 95 per cent both in guinea pigs and rats. Using this method we observed that fasting stress significantly reduced the intensity of skin reaction induced by chemical mediators, heterologous PCA and especially homologous PCA in guinea pigs.", "contents": "A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats. A method for quantitative extraction of extravasated dye from the skin was studied in guinea pigs and rats. A simple method with a low cost and good recovery was established as follows; A piece of the skin containing extravasated dye was soaked overnight in a stoppered glass tube containing 1 ml of 1 N KOH at 37 C. Then, 9 ml of mixed solution of 0.6 N H3PO4 and acetone (5:13) was added to the tube. The tube was shaken vigorously for a few seconds and centrifuged at 3,000 rpm for 15 min. Absorbance of supernatant was measured at 620 nm. The recovery rate of the dye was about 95 per cent both in guinea pigs and rats. Using this method we observed that fasting stress significantly reduced the intensity of skin reaction induced by chemical mediators, heterologous PCA and especially homologous PCA in guinea pigs."}
{"id": "PMID:27709", "title": "[Provocative gamma GT test in chronic pancreatitis? (author's transl)].", "content": "The increase of serum gamma-GT after hormonal stimulation has been reported as a new provocative test in the diagnosis of chronic pancreatitis. The test was suggested to be more sensitive than the serum amylase provocation test. In a clinical study of both tests in 83 consecutive patients the unsensitivity and the high rate of false positive results were demonstrated. Thus these provocation tests do not seem to be valuable in the diagnosis of chronic pancreatitis.", "contents": "[Provocative gamma GT test in chronic pancreatitis? (author's transl)]. The increase of serum gamma-GT after hormonal stimulation has been reported as a new provocative test in the diagnosis of chronic pancreatitis. The test was suggested to be more sensitive than the serum amylase provocation test. In a clinical study of both tests in 83 consecutive patients the unsensitivity and the high rate of false positive results were demonstrated. Thus these provocation tests do not seem to be valuable in the diagnosis of chronic pancreatitis."}
{"id": "PMID:27705", "title": "[Acetic acid, a catabolite repressor of cholinesterase synthesis by an Arthrobacter simplex culture].", "content": "Acetic acid was found to repress cholinesterase synthesis in the cells of Arthrobacter simplex var. cholinesterasus even at very low concentrations (0.1%). The repression is very stable. It is not eliminated by glucose or an organic acid of the Krebs cycle being added to the medium with acetic acid. The combination of acetic and butyric acids decreases the repression but does not eliminate it. The kinetics of cholinesterase synthesis was different in the cells grown on the medium with acetic acid and the cells cultivated on the medium with acetic acid and glucose, then washed and transferred to a fresh growth medium with glucose and acetylcholine as the sources of carbon.", "contents": "[Acetic acid, a catabolite repressor of cholinesterase synthesis by an Arthrobacter simplex culture]. Acetic acid was found to repress cholinesterase synthesis in the cells of Arthrobacter simplex var. cholinesterasus even at very low concentrations (0.1%). The repression is very stable. It is not eliminated by glucose or an organic acid of the Krebs cycle being added to the medium with acetic acid. The combination of acetic and butyric acids decreases the repression but does not eliminate it. The kinetics of cholinesterase synthesis was different in the cells grown on the medium with acetic acid and the cells cultivated on the medium with acetic acid and glucose, then washed and transferred to a fresh growth medium with glucose and acetylcholine as the sources of carbon."}
{"id": "PMID:27710", "title": "[Disorder of porphyrin metabolism in thallium intoxication (author's transl)].", "content": "A 19-year old male ingested in suicidal attempt 750 mg of thallium. He developed the characteristic symptoms of thallium intoxication. During the acute phase the urinary excretion of porphyrins and porphyrin precursors was largely increased. The percentage distribution of the individual metabolites of heme synthesis revealed a preponderance of kopro- and uroporphyrin. This constellation (kopro- greater than uro- greater than tricarboxylic porphyrin) differs appreciably from that one in lead intoxication. The observation of increased urinary excretion of porphyrins and their precursors in a possibly particular spectrum in thallium intoxication is of special interest for differential-diagnostic reasoning. In each case of a toxic disorder of porphyrin metabolism thallium intoxication ought to be considered a possible cause.", "contents": "[Disorder of porphyrin metabolism in thallium intoxication (author's transl)]. A 19-year old male ingested in suicidal attempt 750 mg of thallium. He developed the characteristic symptoms of thallium intoxication. During the acute phase the urinary excretion of porphyrins and porphyrin precursors was largely increased. The percentage distribution of the individual metabolites of heme synthesis revealed a preponderance of kopro- and uroporphyrin. This constellation (kopro- greater than uro- greater than tricarboxylic porphyrin) differs appreciably from that one in lead intoxication. The observation of increased urinary excretion of porphyrins and their precursors in a possibly particular spectrum in thallium intoxication is of special interest for differential-diagnostic reasoning. In each case of a toxic disorder of porphyrin metabolism thallium intoxication ought to be considered a possible cause."}
{"id": "PMID:27706", "title": "[Effect of pH values of the medium unfavorable for growth on the physiological, morphological and cytological characteristics of a chemostat culture of Candida utilis].", "content": "The effect of growth inhibiting values of pH of the medium (pH 2.3 and 7.8) on physiological, morphological and cytological characteristics was studied with the chemostat culture of Candida utilis. Changes in the pH of the medium were accompanied with a decrease in the economic coefficient of the yeast cells, an increase in the respiratory quotient and the activity of phosphohydrolase. Phase-contrast micriscopy has shown that, at acid pH values, the cells were smaller than in the control (in the cells grown under optimal conditions) and rather uniform, oval or rounded, and contained large lipid granules. The presence of large lipid granules was confirmed by electron microscopy; vacuoles were smaller than in the control cells, but their number was greater than one; mitochondria stuck together and had one general outer membrane; the cell wall was 3--4 times thicker. At alkaline pH values of the medium, the whole cellular organization of C. utilis was disordered: the cells were larger, the size of vacuoles increased too much, and the structure became heterogeneous.", "contents": "[Effect of pH values of the medium unfavorable for growth on the physiological, morphological and cytological characteristics of a chemostat culture of Candida utilis]. The effect of growth inhibiting values of pH of the medium (pH 2.3 and 7.8) on physiological, morphological and cytological characteristics was studied with the chemostat culture of Candida utilis. Changes in the pH of the medium were accompanied with a decrease in the economic coefficient of the yeast cells, an increase in the respiratory quotient and the activity of phosphohydrolase. Phase-contrast micriscopy has shown that, at acid pH values, the cells were smaller than in the control (in the cells grown under optimal conditions) and rather uniform, oval or rounded, and contained large lipid granules. The presence of large lipid granules was confirmed by electron microscopy; vacuoles were smaller than in the control cells, but their number was greater than one; mitochondria stuck together and had one general outer membrane; the cell wall was 3--4 times thicker. At alkaline pH values of the medium, the whole cellular organization of C. utilis was disordered: the cells were larger, the size of vacuoles increased too much, and the structure became heterogeneous."}
{"id": "PMID:27707", "title": "[Action of copper ions and of unfavorable medium pH values on protein and RNA synthesis by Candida utilis cells].", "content": "The effect of copper ions and unfavourable pH values of the medium on the incorporation of labelled precursors of protein and RNA was studied in Candida utilis. Specific inhibition of protein synthesis by copper ions and alkaline conditions was found. No specific inhibition of protein or RNA was detected at low pH values of the medium.", "contents": "[Action of copper ions and of unfavorable medium pH values on protein and RNA synthesis by Candida utilis cells]. The effect of copper ions and unfavourable pH values of the medium on the incorporation of labelled precursors of protein and RNA was studied in Candida utilis. Specific inhibition of protein synthesis by copper ions and alkaline conditions was found. No specific inhibition of protein or RNA was detected at low pH values of the medium."}
{"id": "PMID:27713", "title": "Enlarged acid-base and blood gas calculations by electronical data computing in the blood gas laboratory.", "content": "A rapid anaysis of parameters of the acid-base equilibrium and blood gases during open heart surgery and emergency therapy is absolutely necessary. Computing of the several parameters of the acid-base status by slide rules or nomograms is time consuming and can be shortened by computer applications. The central blood gas laboratory consists of a blood gas analyzer for PO2, PCO2 and pH, an electronic desktop calculator, a four color X-Y-plotter and two data lines to the cardiac surgery unit and to the intensive care unit. The time needed for computing and feedback of the parameters could be decreased to one quarter. In addition to numerical data printout, a graphical representation of the several parameters is possible on a X-Y-plotter and includes the Rahn-Fenn-O2-CO2-Diagram with venous admixture, ventilation perfusion ratio, alveolar dead space ventilation and the standard and actual oxygen dissociation curve as well as the pH/HCO3- Acid-Base nomogram. Furthermore, a computer diagnosis of the actual disturbances can be plotted.", "contents": "Enlarged acid-base and blood gas calculations by electronical data computing in the blood gas laboratory. A rapid anaysis of parameters of the acid-base equilibrium and blood gases during open heart surgery and emergency therapy is absolutely necessary. Computing of the several parameters of the acid-base status by slide rules or nomograms is time consuming and can be shortened by computer applications. The central blood gas laboratory consists of a blood gas analyzer for PO2, PCO2 and pH, an electronic desktop calculator, a four color X-Y-plotter and two data lines to the cardiac surgery unit and to the intensive care unit. The time needed for computing and feedback of the parameters could be decreased to one quarter. In addition to numerical data printout, a graphical representation of the several parameters is possible on a X-Y-plotter and includes the Rahn-Fenn-O2-CO2-Diagram with venous admixture, ventilation perfusion ratio, alveolar dead space ventilation and the standard and actual oxygen dissociation curve as well as the pH/HCO3- Acid-Base nomogram. Furthermore, a computer diagnosis of the actual disturbances can be plotted."}
{"id": "PMID:27716", "title": "Characterisation of ribosomal proteins from HeLa and Krebs II mouse ascites tumor cells by different two-dimensional polyacrylamide gel electrophoresis techniques.", "content": "Electrophoresis of ribosomal proteins according to Kaltschmidt and Wittmann, 1970a, b (pH 8.6/pH 4.5 urea system) yielded 29 proteins for the small subunits and 35 and 37 proteins for the large subunits of Krebs II ascites and HeLa ribosomes, respectively. Analysis of the proteins according to a modified technique by Mets and Bogorad (1974) (pH 4.5/pH 8.6 SDS system) revealed 28 and 29 proteins in the small subunits and 37 and 38 proteins in the large subunits of Krebs II ascites and HeLa ribosomes. The molecular weights of the individual proteins were determined by: 1. \"three-dimensional\" gel electrophoresis; 2. two-dimensional gel electrophoresis at pH 4.K/pH 8.6 in SDS. The molecular weights for 40S proteins ranged from 10,000 to 39,000 dalton (number average molecular weight: 21,000). The molecular weights for the 60S proteins ranged from 14,000 to 44,000 dalton (number average molecular weight: 23,000) using the \"three-dimensional\" technique. A molecular weight range from 10,000 to 38,000 dalton (number average molecular weight: 21,000) was obtained for the 40S subunits, whereas the molecular weights for the 60S ribosomal proteins (average molecular weight: 26,000) ranged from 12,000 to 69,000 dalton using the pH 4.5/pH 8.6 SDS system. The molecular weights Krebs II ascites and HeLa ribosomal proteins are compared with those obtained by other authors for different mammalian species.", "contents": "Characterisation of ribosomal proteins from HeLa and Krebs II mouse ascites tumor cells by different two-dimensional polyacrylamide gel electrophoresis techniques. Electrophoresis of ribosomal proteins according to Kaltschmidt and Wittmann, 1970a, b (pH 8.6/pH 4.5 urea system) yielded 29 proteins for the small subunits and 35 and 37 proteins for the large subunits of Krebs II ascites and HeLa ribosomes, respectively. Analysis of the proteins according to a modified technique by Mets and Bogorad (1974) (pH 4.5/pH 8.6 SDS system) revealed 28 and 29 proteins in the small subunits and 37 and 38 proteins in the large subunits of Krebs II ascites and HeLa ribosomes. The molecular weights of the individual proteins were determined by: 1. \"three-dimensional\" gel electrophoresis; 2. two-dimensional gel electrophoresis at pH 4.K/pH 8.6 in SDS. The molecular weights for 40S proteins ranged from 10,000 to 39,000 dalton (number average molecular weight: 21,000). The molecular weights for the 60S proteins ranged from 14,000 to 44,000 dalton (number average molecular weight: 23,000) using the \"three-dimensional\" technique. A molecular weight range from 10,000 to 38,000 dalton (number average molecular weight: 21,000) was obtained for the 40S subunits, whereas the molecular weights for the 60S ribosomal proteins (average molecular weight: 26,000) ranged from 12,000 to 69,000 dalton using the pH 4.5/pH 8.6 SDS system. The molecular weights Krebs II ascites and HeLa ribosomal proteins are compared with those obtained by other authors for different mammalian species."}
{"id": "PMID:27718", "title": "Fidelity of conjugation in Saccharomyces cerevisiae.", "content": "An efficient method for the production of synchronous zygotes in Saccharomyces cerevisiae is described. Cells were synchronised under defined conditions in either an a, alpha mixed culture or by incubation of each mating type in cell-free medium in which cells of the opposite mating type had been grown. Synchronised cells were allowed to fuse under defined conditions on filter membranes. This method was used to test the fidelity of conjugation in S. cerevisiae. Under conditions where cells of a or alpha mating type were in contact with up to 6 cells of each of two strains of opposite mating type, less than 1 multiple mating in 10(4) diploid matings occurred. It is concluded that is sexual conjugation in S. cerevisiae some process distinct from cell contact restricts cell fusion to paired combinations of conjugant cells.", "contents": "Fidelity of conjugation in Saccharomyces cerevisiae. An efficient method for the production of synchronous zygotes in Saccharomyces cerevisiae is described. Cells were synchronised under defined conditions in either an a, alpha mixed culture or by incubation of each mating type in cell-free medium in which cells of the opposite mating type had been grown. Synchronised cells were allowed to fuse under defined conditions on filter membranes. This method was used to test the fidelity of conjugation in S. cerevisiae. Under conditions where cells of a or alpha mating type were in contact with up to 6 cells of each of two strains of opposite mating type, less than 1 multiple mating in 10(4) diploid matings occurred. It is concluded that is sexual conjugation in S. cerevisiae some process distinct from cell contact restricts cell fusion to paired combinations of conjugant cells."}
{"id": "PMID:27717", "title": "Disturbance of the machinery for the gene expression by acidic pH in the repressible acid phosphatase system of Saccharomyces cerevisiae.", "content": "When the pH of growth medium containing a limited amount of inorganic phosphate is kept below 3.0, cells of Saccharomyces cerevisiae produce repressible alkaline phosphatase but no repressible acid phosphatase. The same cells produce acid phosphatase immediately on shifting the medium pH to 4.0 or above. Like intact cells, spheroplasts prepared from cells grown at pH 3.0 or 4.5 in medium with a limited amount of inorganic phosphate in suspension begin production of acid phosphatase immediately after pH shift from below 3.0 to 4.0 whereas sheroplasts from cells grown in inorganic phosphate-rich medium showed a prolonged lag period (3 h). The enzyme formation on the pH shift was sensitive to cycloheximide. No significant differences could be detected in cellular growth or in incorporation of 3H-L-lysine or 14C-adenine between cells cultivated at pH 3.0 and 4.5. These results along with the fact that the expression of structural genes of repressible acid and alkaline phosphatases is controlled by a common genetic regulatory system, at least in part, indicate that the genetic regulatory system operates to express the structural genes even at low pH, though the expression of repressible acid phosphatase is interrupted. Coupled experiments of temperature and pH shifts with the temperature-sensitive mutants of the regulatory genes suggest that the acidic pH affects the function of the cytoplasmic products of those genes in the expression of the structural gene. Based on these observations, a revised model involving the simultaneous functioning of the regulatory factors was suggested for the genetic regulation of repressible acid phosphatase synthesis.", "contents": "Disturbance of the machinery for the gene expression by acidic pH in the repressible acid phosphatase system of Saccharomyces cerevisiae. When the pH of growth medium containing a limited amount of inorganic phosphate is kept below 3.0, cells of Saccharomyces cerevisiae produce repressible alkaline phosphatase but no repressible acid phosphatase. The same cells produce acid phosphatase immediately on shifting the medium pH to 4.0 or above. Like intact cells, spheroplasts prepared from cells grown at pH 3.0 or 4.5 in medium with a limited amount of inorganic phosphate in suspension begin production of acid phosphatase immediately after pH shift from below 3.0 to 4.0 whereas sheroplasts from cells grown in inorganic phosphate-rich medium showed a prolonged lag period (3 h). The enzyme formation on the pH shift was sensitive to cycloheximide. No significant differences could be detected in cellular growth or in incorporation of 3H-L-lysine or 14C-adenine between cells cultivated at pH 3.0 and 4.5. These results along with the fact that the expression of structural genes of repressible acid and alkaline phosphatases is controlled by a common genetic regulatory system, at least in part, indicate that the genetic regulatory system operates to express the structural genes even at low pH, though the expression of repressible acid phosphatase is interrupted. Coupled experiments of temperature and pH shifts with the temperature-sensitive mutants of the regulatory genes suggest that the acidic pH affects the function of the cytoplasmic products of those genes in the expression of the structural gene. Based on these observations, a revised model involving the simultaneous functioning of the regulatory factors was suggested for the genetic regulation of repressible acid phosphatase synthesis."}
{"id": "PMID:27721", "title": "Differential mutagenicity of reaction products of various pyrazolones with nitrite.", "content": "Four pyrazolones in frequent use, i.e. antipyrine (AP), aminopyrine (AMP), sulpyrine (SP) and isopropylantipyrine (IPA), were compared for their reactivity with nitrite and for the in vitro mutagenicity of their reaction products by Ames' reversion tests. In various acidic solutions at 37 degrees C, AP, AMP and SP were found to react easily with nitrite and yield various products including dimethylnitrosamine (DMNA) and 4-nitrosoantipyrine (4-NAP) in the cases of AMP and AP, respectively. When tested with Salmonella typhimurium TA100 and TA98 after lyophilization, the reaction products of AP (AP-N) were found to be mutagenic in both strains, while products of AMP and SP (AMP-N and SP-N) were mutagenic only in TA100. The presence of unknown ultimate mutagens, other than DMNA and 4-NAP, were evidenced in AP-N, AMP-N and SP-N. Incubation with S-9 mixture did not affect the mutagenicity of SP-N and decreased that of AP-N and AMP-N. In clear contrast to AP, AMP and SP, it was found that IPA remained essentially intact upon reaction with nitrite. No mutagenicity was detected with the reaction mixture (IPA-N) in either strain.", "contents": "Differential mutagenicity of reaction products of various pyrazolones with nitrite. Four pyrazolones in frequent use, i.e. antipyrine (AP), aminopyrine (AMP), sulpyrine (SP) and isopropylantipyrine (IPA), were compared for their reactivity with nitrite and for the in vitro mutagenicity of their reaction products by Ames' reversion tests. In various acidic solutions at 37 degrees C, AP, AMP and SP were found to react easily with nitrite and yield various products including dimethylnitrosamine (DMNA) and 4-nitrosoantipyrine (4-NAP) in the cases of AMP and AP, respectively. When tested with Salmonella typhimurium TA100 and TA98 after lyophilization, the reaction products of AP (AP-N) were found to be mutagenic in both strains, while products of AMP and SP (AMP-N and SP-N) were mutagenic only in TA100. The presence of unknown ultimate mutagens, other than DMNA and 4-NAP, were evidenced in AP-N, AMP-N and SP-N. Incubation with S-9 mixture did not affect the mutagenicity of SP-N and decreased that of AP-N and AMP-N. In clear contrast to AP, AMP and SP, it was found that IPA remained essentially intact upon reaction with nitrite. No mutagenicity was detected with the reaction mixture (IPA-N) in either strain."}
{"id": "PMID:27728", "title": "Substance P: binding to lipids in the brain.", "content": "1. Substance P (SP) could be extracted from brain homogenates with chloroform-methanol by a method which extracts all lipids. 2. SP could be transferred form this total lipid extract (TLE) into an aqueous solution at low pH values (2.0--3.0). 3. At higher pH values (5.5) SP could be transferred from an aqueous phase into an organic phase (chloroform:methanol, 2:1) and recombined with TLE (which was previously freed from endogenous SP) contained in this phase. The binding capacity of TLE for SP exceeded by far the amount of endogenous SP bound originally in the brain extracts. 4. Among the lipids present in TLE, phosphatidylserine was able to bind and release SP in a pH dependent manner. 5. It is suggested that SP bound to phosphatidylserine is the storage form of SP in the brain. The mechanisms by which it is released are still unknown. The possibility that the SP-receptor is also a phospholipid is considered.", "contents": "Substance P: binding to lipids in the brain. 1. Substance P (SP) could be extracted from brain homogenates with chloroform-methanol by a method which extracts all lipids. 2. SP could be transferred form this total lipid extract (TLE) into an aqueous solution at low pH values (2.0--3.0). 3. At higher pH values (5.5) SP could be transferred from an aqueous phase into an organic phase (chloroform:methanol, 2:1) and recombined with TLE (which was previously freed from endogenous SP) contained in this phase. The binding capacity of TLE for SP exceeded by far the amount of endogenous SP bound originally in the brain extracts. 4. Among the lipids present in TLE, phosphatidylserine was able to bind and release SP in a pH dependent manner. 5. It is suggested that SP bound to phosphatidylserine is the storage form of SP in the brain. The mechanisms by which it is released are still unknown. The possibility that the SP-receptor is also a phospholipid is considered."}
{"id": "PMID:27729", "title": "The effect of some neuroleptics on the interaction of cortically and nigrally evoked potentials in the rat striatum.", "content": "The interaction of cortico- and nigrofugal inputs to the striatum of the rat was investigated using the technique of evoked potentials. Repetitive, unilateral stimulation of the substantia nigra inhibited potentials which were evoked from the ipsilateral rostral cortex and recorded from the ipsilateral striatum. The inhibition was antagonized by low doses of various intraperitoneally administered neuroleptics such as: pimozide (0.1 - 0.2 mg/kg), haloperidol (0.1 - 0.5 mg/kg), chlorpromazine (0.5 - 2.0 mg/kg) and thioridazine (0.5 - 4.0 mg/kg). These findings are discussed in view of the existing controversy regarding the mode of action of dopamine in the striatum.", "contents": "The effect of some neuroleptics on the interaction of cortically and nigrally evoked potentials in the rat striatum. The interaction of cortico- and nigrofugal inputs to the striatum of the rat was investigated using the technique of evoked potentials. Repetitive, unilateral stimulation of the substantia nigra inhibited potentials which were evoked from the ipsilateral rostral cortex and recorded from the ipsilateral striatum. The inhibition was antagonized by low doses of various intraperitoneally administered neuroleptics such as: pimozide (0.1 - 0.2 mg/kg), haloperidol (0.1 - 0.5 mg/kg), chlorpromazine (0.5 - 2.0 mg/kg) and thioridazine (0.5 - 4.0 mg/kg). These findings are discussed in view of the existing controversy regarding the mode of action of dopamine in the striatum."}
{"id": "PMID:27734", "title": "The treatment of anxiety with a polyfluorinated benzodiazepine derivative.", "content": "Following 4 weeks of treatment with ORF-8063 a polyfluorinated benzodiazepine derivative, 8 hospitalized patients manifesting a primary pathology of anxiety showed marked general improvement. 2 other persons were treated, but for shorter periods: 9 and 14 days. Both are included in the pre-post analysis. Mean optimal dosage was 66.5 mg. The five instruments used to measure therapeutic effect showed pre- to posttreatment change with high level of statistical significance in serveral of the pathological factors. When measures of change are considered, patients showed more improvement related to psychic than somatic components of anxiety. Change data also indicates more patients improvement in anxiety than depression. Side effects reported more were dizziness, faintness and insomnia; these were reported in 8 patients. 6 patients noted drowsiness, and 4 noted excitement. 5 persons tolerated optimum dosages with no extreme reactions; 5 others (including the 2 subjects who terminated treatment early) were unable to maintain optimum dosages because of side effects.", "contents": "The treatment of anxiety with a polyfluorinated benzodiazepine derivative. Following 4 weeks of treatment with ORF-8063 a polyfluorinated benzodiazepine derivative, 8 hospitalized patients manifesting a primary pathology of anxiety showed marked general improvement. 2 other persons were treated, but for shorter periods: 9 and 14 days. Both are included in the pre-post analysis. Mean optimal dosage was 66.5 mg. The five instruments used to measure therapeutic effect showed pre- to posttreatment change with high level of statistical significance in serveral of the pathological factors. When measures of change are considered, patients showed more improvement related to psychic than somatic components of anxiety. Change data also indicates more patients improvement in anxiety than depression. Side effects reported more were dizziness, faintness and insomnia; these were reported in 8 patients. 6 patients noted drowsiness, and 4 noted excitement. 5 persons tolerated optimum dosages with no extreme reactions; 5 others (including the 2 subjects who terminated treatment early) were unable to maintain optimum dosages because of side effects."}
{"id": "PMID:27735", "title": "Duration of apnea needed to confirm brain death.", "content": "To determine the duration of respiratory arrest needed to attain a PaCO2 level high enough to provide maximal stimulation of respiration, we evaluated changes in PaCO2, PaO2 and apH during periods of apnea lasting as long as 10 minutes in 10 apparently brain-dead subjects. Before apnea, mean PaCO2 was 33 mm Hg. In seven subjects who did not breathe for 10 minutes, the mean rate of rise of PaCO2 was 3.2 mm Hg per minute. PaCO2 at 4 minutes was 50 mm Hg and at 10 minutes was 67 mm Hg. Three subjects breathed, two after less than 2 minutes of apnea, when PaCO2 was 47 and 54 mm Hg, and one after 4.5 minutes, when PaCO2 was 47 mm Hg. These data indicate: (1) that the threshold for respiratory stimulation may approach a PaCO2 of 60 mm Hg in patients with brain damage; (2) that the rate of increase in PaCO2 is such that, even in a normocapnic subject after 3 minutes of apnea, the PaCO2 may not be sufficiently high to stimulate respiration; and (3) if a patient is hypocapnic prior to the onset of apnea, PaCO2 may not reach 60 mm Hg even after 15 minutes. To confirm absolute apnea, then, blood gas monitoring is necessary for verification of normocapnia prior to the beginning of apnea. In the absence of blood gas determinations, no fixed period of apnea, sufficient in all cases to establish absolute apnea, can be ascertained.", "contents": "Duration of apnea needed to confirm brain death. To determine the duration of respiratory arrest needed to attain a PaCO2 level high enough to provide maximal stimulation of respiration, we evaluated changes in PaCO2, PaO2 and apH during periods of apnea lasting as long as 10 minutes in 10 apparently brain-dead subjects. Before apnea, mean PaCO2 was 33 mm Hg. In seven subjects who did not breathe for 10 minutes, the mean rate of rise of PaCO2 was 3.2 mm Hg per minute. PaCO2 at 4 minutes was 50 mm Hg and at 10 minutes was 67 mm Hg. Three subjects breathed, two after less than 2 minutes of apnea, when PaCO2 was 47 and 54 mm Hg, and one after 4.5 minutes, when PaCO2 was 47 mm Hg. These data indicate: (1) that the threshold for respiratory stimulation may approach a PaCO2 of 60 mm Hg in patients with brain damage; (2) that the rate of increase in PaCO2 is such that, even in a normocapnic subject after 3 minutes of apnea, the PaCO2 may not be sufficiently high to stimulate respiration; and (3) if a patient is hypocapnic prior to the onset of apnea, PaCO2 may not reach 60 mm Hg even after 15 minutes. To confirm absolute apnea, then, blood gas monitoring is necessary for verification of normocapnia prior to the beginning of apnea. In the absence of blood gas determinations, no fixed period of apnea, sufficient in all cases to establish absolute apnea, can be ascertained."}
{"id": "PMID:27736", "title": "Thiamine deficiency: selective impairment of the cerebellar serotonergic system.", "content": "To explore the role of thiamine deficiency in synaptic transmission, the high-affinity uptake and release systems for putative neurotransmitters were studied in synaptosomal preparations isolated from the telencephalon, hypothalamus, and cerebellum of rats made thiamine deficient by diet or pyrithiamine. There was significant decrease in the uptake of serotonin by the synaptosomal preparations of the cerebellum. Although thiamine and its phosphorylated forms added in vitro did not restore the decreased serotonin uptake, the administration of the vitamin in vivo resulted in a significant reversibility of the inhibition of serotonin uptake, coinciding with dramatic clinical improvement. The study supports the possibility of an important serotonergic innervation of the cerebellum and suggests a selective involvement of this system in the pathogenesis of some of the neurologic manifestations of thiamine deficiency.", "contents": "Thiamine deficiency: selective impairment of the cerebellar serotonergic system. To explore the role of thiamine deficiency in synaptic transmission, the high-affinity uptake and release systems for putative neurotransmitters were studied in synaptosomal preparations isolated from the telencephalon, hypothalamus, and cerebellum of rats made thiamine deficient by diet or pyrithiamine. There was significant decrease in the uptake of serotonin by the synaptosomal preparations of the cerebellum. Although thiamine and its phosphorylated forms added in vitro did not restore the decreased serotonin uptake, the administration of the vitamin in vivo resulted in a significant reversibility of the inhibition of serotonin uptake, coinciding with dramatic clinical improvement. The study supports the possibility of an important serotonergic innervation of the cerebellum and suggests a selective involvement of this system in the pathogenesis of some of the neurologic manifestations of thiamine deficiency."}
{"id": "PMID:27745", "title": "[Infestation of mosquitoes from the Maritime Territory by the entomopathogenic fungus, Coelomomyces iliensis, under laboratory conditions].", "content": "The infection of larvae of Culex pipiens molestus, C. vagans and C. tritaeniorhynchus (the vector of the virus of Japanese encephalitis) with the entomopathogenic fungus Coelomomyces iliensis from Kazakhstan was carried out in the Primorje Territory in 1973--1974. At the infection of larvae of C. tritaeniorhynchus with the suspension of infected larvae the mortality was recorded only from 60% of individuals, while at the infection with a content of sporangia--from 36.6% of larvae. Somewhat less mortality (27.5%) was observed among larvae of C. pipiens molestus and C. pipiens. In control the mortali larvae did not exceed 5%.", "contents": "[Infestation of mosquitoes from the Maritime Territory by the entomopathogenic fungus, Coelomomyces iliensis, under laboratory conditions]. The infection of larvae of Culex pipiens molestus, C. vagans and C. tritaeniorhynchus (the vector of the virus of Japanese encephalitis) with the entomopathogenic fungus Coelomomyces iliensis from Kazakhstan was carried out in the Primorje Territory in 1973--1974. At the infection of larvae of C. tritaeniorhynchus with the suspension of infected larvae the mortality was recorded only from 60% of individuals, while at the infection with a content of sporangia--from 36.6% of larvae. Somewhat less mortality (27.5%) was observed among larvae of C. pipiens molestus and C. pipiens. In control the mortali larvae did not exceed 5%."}
{"id": "PMID:27752", "title": "Interaction of peripheral and central respiratory drives in cats. I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH.", "content": "In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.02, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 microgram sodium cyanide in 200 microliter Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated that the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of VT and V to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors.", "contents": "Interaction of peripheral and central respiratory drives in cats. I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH. In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.02, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 microgram sodium cyanide in 200 microliter Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated that the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of VT and V to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors."}
{"id": "PMID:27756", "title": "[Gastric acid secretion by vagal electrostimulation (author's transl)].", "content": "In the operative verification of vagotomy, electrical stimulation of the vagus nerves with the study of pH should seem to be a reliable method. On the basis of an experiment in the cat, the authors emphasise the effectiveness of electrical stimulation of gastric acid secretion, confirmed by 16 clinical cases. Stimulation of the proximal end of the divided right nerve may be used to detect a nervous strand arising above the level of the section and to confirm the completeness of left vagotomy.", "contents": "[Gastric acid secretion by vagal electrostimulation (author's transl)]. In the operative verification of vagotomy, electrical stimulation of the vagus nerves with the study of pH should seem to be a reliable method. On the basis of an experiment in the cat, the authors emphasise the effectiveness of electrical stimulation of gastric acid secretion, confirmed by 16 clinical cases. Stimulation of the proximal end of the divided right nerve may be used to detect a nervous strand arising above the level of the section and to confirm the completeness of left vagotomy."}
{"id": "PMID:27761", "title": "Protonated polynucleotides structures - 22.CD study of the acid-base titration of poly(dG).poly(dC).", "content": "The acid-base titration (pH 8 --> pH 2.5 --> pH 8) of eleven mixing curve samples of the poly(dG) plus poly(dC) system has been performed in 0.15 M NaCl. Upon protonation, poly(dG).poly(dC) gives rise to an acid complex, in various amounts according to the origin of the sample. We have established that the hysteresis of the acid-base titration is due to the non-reversible formation of an acid complex, and the liberation of the homopolymers at the end of the acid titration and during the base titration: the homopolymer mixtures remain stable up to pH 7. A 1G:1C stoichiometry appears to be the most probable for the acid complex, a 1G:2C stoichiometry, as found in poly(C(+)).poly(I).poly(C) or poly(C(+)).poly(G).poly(C), cannot be rejected. In the course of this study, evidence has been found that the structural consequences of protonation could be similar for both double stranded poly(dG).poly(dC) and G-C rich DNA's: 1) protonation starts near pH 6, dissociation of the acid complex of poly(dG).poly(dC) and of protonated DNA take place at pH 3; 2) the CD spectrum computed for the acid polymer complex displays a positive peak at 255 nm as found in the acid spectra of DNA's; 3) double stranded poly(dG).poly(dC) embedded in triple-stranded poly(dG).poly(dG).poly(dC) should be in the A-form and appears to be prevented from the proton induced conformational change. The neutral triple stranded poly(dG).poly(dG).poly(dC) appears therefore responsible, although indirectly, for the complexity and variability of the acid titration of poly(dG).poly(dC) samples.", "contents": "Protonated polynucleotides structures - 22.CD study of the acid-base titration of poly(dG).poly(dC). The acid-base titration (pH 8 --> pH 2.5 --> pH 8) of eleven mixing curve samples of the poly(dG) plus poly(dC) system has been performed in 0.15 M NaCl. Upon protonation, poly(dG).poly(dC) gives rise to an acid complex, in various amounts according to the origin of the sample. We have established that the hysteresis of the acid-base titration is due to the non-reversible formation of an acid complex, and the liberation of the homopolymers at the end of the acid titration and during the base titration: the homopolymer mixtures remain stable up to pH 7. A 1G:1C stoichiometry appears to be the most probable for the acid complex, a 1G:2C stoichiometry, as found in poly(C(+)).poly(I).poly(C) or poly(C(+)).poly(G).poly(C), cannot be rejected. In the course of this study, evidence has been found that the structural consequences of protonation could be similar for both double stranded poly(dG).poly(dC) and G-C rich DNA's: 1) protonation starts near pH 6, dissociation of the acid complex of poly(dG).poly(dC) and of protonated DNA take place at pH 3; 2) the CD spectrum computed for the acid polymer complex displays a positive peak at 255 nm as found in the acid spectra of DNA's; 3) double stranded poly(dG).poly(dC) embedded in triple-stranded poly(dG).poly(dG).poly(dC) should be in the A-form and appears to be prevented from the proton induced conformational change. The neutral triple stranded poly(dG).poly(dG).poly(dC) appears therefore responsible, although indirectly, for the complexity and variability of the acid titration of poly(dG).poly(dC) samples."}
{"id": "PMID:27762", "title": "Protonated polynucleotides structures - 23. The acid-base hysteresis of poly(dG).poly(dC).", "content": "The large hysteresis observed during the acid-base titration of poly(dG). poly (dC) was studied by CD and potentiometric scanning curves. Intermediate scanning loops as well as the equilibrium and metastable branches of the hysteresis loop have been determined. The potentiometric titrations showed, however, that the various complexes were not discrete entities, but were linked in \"polycomplexes\" as had been already suggested. This prevented a thermodynamic study of the system. The acid-base titration was further investigated as a function of ionic strength and temperature. The pK's showed considerably lower ionic strength dependence than observed for polyribonucleotide complexes. The thermal transitions permitted to establish the relative stabilities of the various complexes between pH 2.5 and pH 12.0.", "contents": "Protonated polynucleotides structures - 23. The acid-base hysteresis of poly(dG).poly(dC). The large hysteresis observed during the acid-base titration of poly(dG). poly (dC) was studied by CD and potentiometric scanning curves. Intermediate scanning loops as well as the equilibrium and metastable branches of the hysteresis loop have been determined. The potentiometric titrations showed, however, that the various complexes were not discrete entities, but were linked in \"polycomplexes\" as had been already suggested. This prevented a thermodynamic study of the system. The acid-base titration was further investigated as a function of ionic strength and temperature. The pK's showed considerably lower ionic strength dependence than observed for polyribonucleotide complexes. The thermal transitions permitted to establish the relative stabilities of the various complexes between pH 2.5 and pH 12.0."}
{"id": "PMID:27763", "title": "Cross-linking of nucleosomal histones with monofunctional imidoesters.", "content": "Cross-linking experiments with the MONOfunctional imidoester methyl-acetimidate, in the pH range 7.0 - 8.0, on rat liver nucleosomes generate a cross-linking pattern almost identical with the one observed for much longer BIfunctional reagents (e.g. dimethylsuberimidate). Combined cross-linking and trypsin digestion experiments suggest that all or at least the great majority of this cross-linking occurs on trypsin digestible segments (or \"tails\") of the histones. The formation of oligomers over such extremely short distances and especially the observation of an H3 homodimer suggests a very close proximity of half-nucleosomes.", "contents": "Cross-linking of nucleosomal histones with monofunctional imidoesters. Cross-linking experiments with the MONOfunctional imidoester methyl-acetimidate, in the pH range 7.0 - 8.0, on rat liver nucleosomes generate a cross-linking pattern almost identical with the one observed for much longer BIfunctional reagents (e.g. dimethylsuberimidate). Combined cross-linking and trypsin digestion experiments suggest that all or at least the great majority of this cross-linking occurs on trypsin digestible segments (or \"tails\") of the histones. The formation of oligomers over such extremely short distances and especially the observation of an H3 homodimer suggests a very close proximity of half-nucleosomes."}
{"id": "PMID:27764", "title": "An efficient in vitro total reconstitution of the Escherichia coli 50S ribosomal subunit.", "content": "A new, relatively simple technique for the total invitro reconstitution of E. coli 50S ribosomes has been developed. It is a two-step procedure like that previously reported by Nierhaus and Dohme [Proc. Natl. Acad. Sci. 71, 4713 (1974)], but it differs in a number of important aspects. Ribosomal RNA is prepared by direct phenol extraction of 70S particles to minimize nuclease fragmentation. A mixture of 50S proteins is prepared by acetic acid extraction and immediate removal of the acetic acid by thin film dialysis. The resulting protein mixture is soluble and stable. Separate RNA and protein fractions are mixed, incubated first at 44 degrees C in 7.5 mM Mg(2+), and then at 50 degrees C in 20 mM Mg(2+). The resulting 50S particles comigrate with native 50S particles in analytical gradients. They range from 50 to 100% active in five different functional assays. This is a fairly stringent test of the effectiveness of reconstitution since 50S particles derived from highly active vacant couples were used as a control.Images", "contents": "An efficient in vitro total reconstitution of the Escherichia coli 50S ribosomal subunit. A new, relatively simple technique for the total invitro reconstitution of E. coli 50S ribosomes has been developed. It is a two-step procedure like that previously reported by Nierhaus and Dohme [Proc. Natl. Acad. Sci. 71, 4713 (1974)], but it differs in a number of important aspects. Ribosomal RNA is prepared by direct phenol extraction of 70S particles to minimize nuclease fragmentation. A mixture of 50S proteins is prepared by acetic acid extraction and immediate removal of the acetic acid by thin film dialysis. The resulting protein mixture is soluble and stable. Separate RNA and protein fractions are mixed, incubated first at 44 degrees C in 7.5 mM Mg(2+), and then at 50 degrees C in 20 mM Mg(2+). The resulting 50S particles comigrate with native 50S particles in analytical gradients. They range from 50 to 100% active in five different functional assays. This is a fairly stringent test of the effectiveness of reconstitution since 50S particles derived from highly active vacant couples were used as a control.Images"}
{"id": "PMID:27765", "title": "The isolation of duplex DNA fragments containing (dG.dC) clusters by chromatography on poly(rC)-Sephadex.", "content": "Duplex DNA containing oligo(dG.dC)-rich clusters can be isolated by specific binding to poly(rC)-Sephadex. This binding, probably mediated by the formation of an oligo(dG.dC)rC+ triple helix, is optimal at pH 5 in 50% formamide, 2 M LiCl; the bound DNA is recovered by elution at pH 7.5. Using this method we find that the viral DNAs PM2, lambda and SV40 contain at least 1, 1 and 2 sites for binding to poly(rC)-Sephadex, respectively. These binding sites have been mapped in the case of SV40; the binding sites can in turn be used for physical mapping studies of DNAs containing (dG.dC) clusters. Inspection of the sequence of the bound fragments of SV40 DNA shows that a (dG.dC)6-7 tract is required for the binding of duplex DNA to poly(rC)-Sephadex. Although about 60% of rabbit DNA cleaved with restriction endonuclease KpnI binds to poly(rC)-Sephadex, no binding is observed for the 5.1 kb DNA fragment generated by KpnI digestion, which contains the rabbit beta-globin gene. This indicates that oligo(dG.dC) clusters are not found close to the rabbit beta-globin gene.", "contents": "The isolation of duplex DNA fragments containing (dG.dC) clusters by chromatography on poly(rC)-Sephadex. Duplex DNA containing oligo(dG.dC)-rich clusters can be isolated by specific binding to poly(rC)-Sephadex. This binding, probably mediated by the formation of an oligo(dG.dC)rC+ triple helix, is optimal at pH 5 in 50% formamide, 2 M LiCl; the bound DNA is recovered by elution at pH 7.5. Using this method we find that the viral DNAs PM2, lambda and SV40 contain at least 1, 1 and 2 sites for binding to poly(rC)-Sephadex, respectively. These binding sites have been mapped in the case of SV40; the binding sites can in turn be used for physical mapping studies of DNAs containing (dG.dC) clusters. Inspection of the sequence of the bound fragments of SV40 DNA shows that a (dG.dC)6-7 tract is required for the binding of duplex DNA to poly(rC)-Sephadex. Although about 60% of rabbit DNA cleaved with restriction endonuclease KpnI binds to poly(rC)-Sephadex, no binding is observed for the 5.1 kb DNA fragment generated by KpnI digestion, which contains the rabbit beta-globin gene. This indicates that oligo(dG.dC) clusters are not found close to the rabbit beta-globin gene."}
{"id": "PMID:27766", "title": "Histone H1--DNA interaction. On the mechanism of DNA strands crosslinking by histone H1.", "content": "Crosslinking of DNA fibers by histone H1 or phosphorylated on Ser-37 histone H1, and by the individual fragments of the H1 polypeptide chain was studied by the method of turbidimetry. The dependence of the turbidity of DNA-protein complexes on the ionic strength in solution suggests that the condensation of H1.DNA complexes in vitro is apparently due to both specific histone-DNA interactions with the contribution of hydrogen and/or hydrophobic bonds and the formation of polycationic \"bridges\" fastening the DNA fibers. The effectiveness of the condensation is postulated to be a function of a proportion between the two mechanisms which in turn can be controlled by slight changes in ionic surroundings. The sharp dependence of shrinkage of H1.DNA complexes on ionic strength at \"physiological\" salt concentrations could provide a mechanism to regulate density and consequently the total activity of chromatin in the cell nuclei. The phosphorylation of histone H1 on Ser-37 by a specific histone kinase does not noticeably affect the pattern of DNA crosslinking by the H1.", "contents": "Histone H1--DNA interaction. On the mechanism of DNA strands crosslinking by histone H1. Crosslinking of DNA fibers by histone H1 or phosphorylated on Ser-37 histone H1, and by the individual fragments of the H1 polypeptide chain was studied by the method of turbidimetry. The dependence of the turbidity of DNA-protein complexes on the ionic strength in solution suggests that the condensation of H1.DNA complexes in vitro is apparently due to both specific histone-DNA interactions with the contribution of hydrogen and/or hydrophobic bonds and the formation of polycationic \"bridges\" fastening the DNA fibers. The effectiveness of the condensation is postulated to be a function of a proportion between the two mechanisms which in turn can be controlled by slight changes in ionic surroundings. The sharp dependence of shrinkage of H1.DNA complexes on ionic strength at \"physiological\" salt concentrations could provide a mechanism to regulate density and consequently the total activity of chromatin in the cell nuclei. The phosphorylation of histone H1 on Ser-37 by a specific histone kinase does not noticeably affect the pattern of DNA crosslinking by the H1."}
{"id": "PMID:27767", "title": "In vitro transcription in E. coli crude lysates prepared on cellophane discs.", "content": "An in vitro RNA-synthesizing system consisting of gently lysed E. coli cells on cellophane discs is described. The system has been optimalized with respect to total RNA synthesis. Under certain standard conditions DNA dependent RNA polymerase (EC 2.7.7.6) is responsible for the majority of the RNA synthesis. The extensive rifampicin sensitivity of the synthesis indicates that most of the transcripts are initiated in vitro. The RNA synthesizing system described here has been developed with the aim of studying phage transcription in vitro. We show here that lysates of a P4 infected P2 lysogen support initiation and propagation of transcription from the P2 prophage.", "contents": "In vitro transcription in E. coli crude lysates prepared on cellophane discs. An in vitro RNA-synthesizing system consisting of gently lysed E. coli cells on cellophane discs is described. The system has been optimalized with respect to total RNA synthesis. Under certain standard conditions DNA dependent RNA polymerase (EC 2.7.7.6) is responsible for the majority of the RNA synthesis. The extensive rifampicin sensitivity of the synthesis indicates that most of the transcripts are initiated in vitro. The RNA synthesizing system described here has been developed with the aim of studying phage transcription in vitro. We show here that lysates of a P4 infected P2 lysogen support initiation and propagation of transcription from the P2 prophage."}
{"id": "PMID:27775", "title": "Hospital phobia: a rapid desensitization technique.", "content": "The less disabling phobias do not normally present a problem in that the stimulus may be avoided. This would also apply to hospital phobia until an acute medical or surgical problem might arise, when avoidance could constitute a direct threat to life. Although phobic illness is a common problem the small number of cases of hospital phobia recorded may represent the tip of the iceberg beneath which could be many phobic patients who deny their symptoms and risk their health because of their irrational fear. A case of hopsital phobia in a pregnant patient with suspected disproportion was treated by a rapid desensitization technique using hypnosis. After five sessions of 30 min each, the patient was symptom free. This simple method of desensitization, if more widely known would considerably minimize the risk caused by concealment of the phobic problem.", "contents": "Hospital phobia: a rapid desensitization technique. The less disabling phobias do not normally present a problem in that the stimulus may be avoided. This would also apply to hospital phobia until an acute medical or surgical problem might arise, when avoidance could constitute a direct threat to life. Although phobic illness is a common problem the small number of cases of hospital phobia recorded may represent the tip of the iceberg beneath which could be many phobic patients who deny their symptoms and risk their health because of their irrational fear. A case of hopsital phobia in a pregnant patient with suspected disproportion was treated by a rapid desensitization technique using hypnosis. After five sessions of 30 min each, the patient was symptom free. This simple method of desensitization, if more widely known would considerably minimize the risk caused by concealment of the phobic problem."}
{"id": "PMID:27779", "title": "[Effect of cultivation temperature and pH on the biosynthesis of extracellular phosphohydrolases by the culture Penicillium brevi-compactum].", "content": "The effect of cultivation temperature and pH on growth of the culture Penicillium brevi-compactum and biosynthesis of extracellular phosphohydrolases (acid and alkaline RNases and acid PMEase) involved in RNA degradation was studied. The maximum growth of the culture was seen at 30 degrees and pA-7.0 and its maximum physiological activity with respect to the above enzymes was noted at 24 degrees and pH = 3.0, i.e. optimal conditions for the biosynthesis of phosphohydrolases did not coincide with those for the culture growth. The cultivation temperature and pH produced an effect on the oxygen consumption and synthesis of extracellular phosphohydrolases by the culture.", "contents": "[Effect of cultivation temperature and pH on the biosynthesis of extracellular phosphohydrolases by the culture Penicillium brevi-compactum]. The effect of cultivation temperature and pH on growth of the culture Penicillium brevi-compactum and biosynthesis of extracellular phosphohydrolases (acid and alkaline RNases and acid PMEase) involved in RNA degradation was studied. The maximum growth of the culture was seen at 30 degrees and pA-7.0 and its maximum physiological activity with respect to the above enzymes was noted at 24 degrees and pH = 3.0, i.e. optimal conditions for the biosynthesis of phosphohydrolases did not coincide with those for the culture growth. The cultivation temperature and pH produced an effect on the oxygen consumption and synthesis of extracellular phosphohydrolases by the culture."}
{"id": "PMID:27783", "title": "Hydrolysis of poly (A) to adenine nucleotides by purified poly (A) polymerase.", "content": "Highly purified poly(A) polymerase (polynucleotide adenylyltransferase, EC 2.7.7.19), which synthesizes poly(A) from ATP substrate, can also catalyze hydrolysis of poly(A). The enzyme, designated as poly(A) hydrolase, requires either Mn2+ or Mg2+ for activity. Although AMP is the predominant product of the reaction, ADP and ATP are also formed. The enzyme is a 3'-exonuclease that does not degrade poly(A) associated with poly(A) poly(U) helical structure. AMP, ADP, and ATP inhibit the hydrolytic reaction. These data suggest that (i) the levels of adenine nucleotides regulate synthesis and degradation of poly(A), (ii) poly(A) itself is a storage form of adenine nucleotides, (iii) the hydrolytic reaction is responsible for poly(A) shortening or turnover observed in vivo, and (iv) the synthetic and hydrolytic activities are functions of the same protein molecule.", "contents": "Hydrolysis of poly (A) to adenine nucleotides by purified poly (A) polymerase. Highly purified poly(A) polymerase (polynucleotide adenylyltransferase, EC 2.7.7.19), which synthesizes poly(A) from ATP substrate, can also catalyze hydrolysis of poly(A). The enzyme, designated as poly(A) hydrolase, requires either Mn2+ or Mg2+ for activity. Although AMP is the predominant product of the reaction, ADP and ATP are also formed. The enzyme is a 3'-exonuclease that does not degrade poly(A) associated with poly(A) poly(U) helical structure. AMP, ADP, and ATP inhibit the hydrolytic reaction. These data suggest that (i) the levels of adenine nucleotides regulate synthesis and degradation of poly(A), (ii) poly(A) itself is a storage form of adenine nucleotides, (iii) the hydrolytic reaction is responsible for poly(A) shortening or turnover observed in vivo, and (iv) the synthetic and hydrolytic activities are functions of the same protein molecule."}
{"id": "PMID:27780", "title": "[Examination of the action of effectors after storing glutamine synthetase from the fodder yeast Candida tropicalis at room temperature].", "content": "The pattern of action of effectors (AMP, IMP, CMP, anthranilic acid, tryptophane, alanine, glutamine, glycine, histidine) and glutamine synthetase (GS) extracted from the fodder yeast Candida tropicalis and stored at room temperature for 1.5-2 hrs was examined. As regards the action of effectors on GS after its exposure at room temperature, they can be subdivided into four groups: 1) the effector loses completely its inhibitory effect (glutamine, CMP, anthranilic acid in the synthetase reaction); 2) the inhibitory effect on the enzyme increases (AMP, IMP, anthranilic acid in the transferase reaction); 3) at low concentrations of the effector the peak of activation appears (tryptophane, GMP, alanine, glycine); 4) at low concentrations of the enzyme two peaks of activation appear (histidine). Similar results were obtained with the purified preparation of GS.", "contents": "[Examination of the action of effectors after storing glutamine synthetase from the fodder yeast Candida tropicalis at room temperature]. The pattern of action of effectors (AMP, IMP, CMP, anthranilic acid, tryptophane, alanine, glutamine, glycine, histidine) and glutamine synthetase (GS) extracted from the fodder yeast Candida tropicalis and stored at room temperature for 1.5-2 hrs was examined. As regards the action of effectors on GS after its exposure at room temperature, they can be subdivided into four groups: 1) the effector loses completely its inhibitory effect (glutamine, CMP, anthranilic acid in the synthetase reaction); 2) the inhibitory effect on the enzyme increases (AMP, IMP, anthranilic acid in the transferase reaction); 3) at low concentrations of the effector the peak of activation appears (tryptophane, GMP, alanine, glycine); 4) at low concentrations of the enzyme two peaks of activation appear (histidine). Similar results were obtained with the purified preparation of GS."}
{"id": "PMID:27781", "title": "[Kinetics and stability of glucooxidase from Penicillium vitale].", "content": "The kinetics, thermal stability and ultrasonic resistance of glucosoxidase from Penicillium vitale have been investigated. Its oxidative constant is close to, catalytic constant is 1.7 times less and the reductive constant is 5.4 times more than the respective constants of the enzyme from Aspergillus niger. The relationship between the thermal inactivation constant (k(i)=2.1 pT 15.3. The same relationship is true of the ultrasonic inactivation constant and pH in the pH range of 6.5-8.0. In a more acidic medium the rate of ultrasonic inactivation shows an insignificant dependence on pH. The mechanism of enzyme inactivation is discussed.", "contents": "[Kinetics and stability of glucooxidase from Penicillium vitale]. The kinetics, thermal stability and ultrasonic resistance of glucosoxidase from Penicillium vitale have been investigated. Its oxidative constant is close to, catalytic constant is 1.7 times less and the reductive constant is 5.4 times more than the respective constants of the enzyme from Aspergillus niger. The relationship between the thermal inactivation constant (k(i)=2.1 pT 15.3. The same relationship is true of the ultrasonic inactivation constant and pH in the pH range of 6.5-8.0. In a more acidic medium the rate of ultrasonic inactivation shows an insignificant dependence on pH. The mechanism of enzyme inactivation is discussed."}
{"id": "PMID:27784", "title": "Isolation of a low molecular weight Ca2+ carrier from calf heart inner mitochondrial membrane.", "content": "A protein was isolated from calf heart inner mitochondrial membrane with the aid of an electron paramagnetic resonance assay based on the relative binding properties of Ca2+, Mn2+, and Mg2+ to the protein. The molecular weight of this protein has been estimated to be about 3000 by urea/sodium dodecyl sulfate gel electrophoresis and amino acid analysis. The protein is shown to have two classes of binding sites for Ca2+ by flow dialysis studies and can extract Ca2+ into an organic phase. The selectivity sequence of this protein determined from the organic solvent extraction experiments shows that it favors divalent cations over monovalent cations. Also, the relative selectivity sequence for divalent cations is Ca2+, Sr2+ greater than Mn2+ greater than Mg2+. Ruthenium red and La3+ are shown to inhibit the protein-mediated extraction of Ca2+ into the organic solvent. The calcium translocation in a Pressman cell by this protein is selectively driven by a hydrogen ion gradient. Control experiments indicate that the Ca2+ trnsport properties of the protein are not due to the contaminating phospholipids. It appears that we have isolated from the inner mitochondrial membrane a calcium carrier, which we have named \"calciphorin.\"", "contents": "Isolation of a low molecular weight Ca2+ carrier from calf heart inner mitochondrial membrane. A protein was isolated from calf heart inner mitochondrial membrane with the aid of an electron paramagnetic resonance assay based on the relative binding properties of Ca2+, Mn2+, and Mg2+ to the protein. The molecular weight of this protein has been estimated to be about 3000 by urea/sodium dodecyl sulfate gel electrophoresis and amino acid analysis. The protein is shown to have two classes of binding sites for Ca2+ by flow dialysis studies and can extract Ca2+ into an organic phase. The selectivity sequence of this protein determined from the organic solvent extraction experiments shows that it favors divalent cations over monovalent cations. Also, the relative selectivity sequence for divalent cations is Ca2+, Sr2+ greater than Mn2+ greater than Mg2+. Ruthenium red and La3+ are shown to inhibit the protein-mediated extraction of Ca2+ into the organic solvent. The calcium translocation in a Pressman cell by this protein is selectively driven by a hydrogen ion gradient. Control experiments indicate that the Ca2+ trnsport properties of the protein are not due to the contaminating phospholipids. It appears that we have isolated from the inner mitochondrial membrane a calcium carrier, which we have named \"calciphorin.\""}
{"id": "PMID:27785", "title": "31P nuclear magnetic resonance studies of bioenergetics and glycolysis in anaerobic Escherichia coli cells.", "content": "31P nuclear magnetic resonance spectra of glycolyzing, anaerobic Escherichia coli cells and their perchloric acid extracts were obtained at 145.7 MHz. Time-dependent intracellular concentrations of nucleoside di- and triphosphates, Pi, and sugar phosphates were measured during glycolysis with 2-min resolution, while intracellular and extra-cellular pH values were monitored simultaneously. Upon glucose addition, anaerobic E. coli cells rapidly produce acids and develop a transmembrane pH gradient (delta pH). Glycolysis rates were calculated from the changes in the external pH. It was found that glycolysis rates are strongly dependent on internal pH, sharply decreasing when the pH drops below approximately 7.2. The ATPase inhibitor, dicyclohexylcarbodiimide (DCCD), prevented NTP hydrolysis and inhibited delta pH formation. The uncoupler, carbonyl cyanide p-triflouromethoxyphenyl hydrazone (FCCP), drastically reduced both the delta pH and the NTP level. When the cells were previously treated with DCCD, FCCP collapsed the delta pH while the NTP levels remained high. It is concluded that ATP produced by glycolysis is hydrolyzed by the membrane ATPase to generate a delta pH and that FCCP stimulates ATP hydrolysis by ATPase and collapses the proton gradient.", "contents": "31P nuclear magnetic resonance studies of bioenergetics and glycolysis in anaerobic Escherichia coli cells. 31P nuclear magnetic resonance spectra of glycolyzing, anaerobic Escherichia coli cells and their perchloric acid extracts were obtained at 145.7 MHz. Time-dependent intracellular concentrations of nucleoside di- and triphosphates, Pi, and sugar phosphates were measured during glycolysis with 2-min resolution, while intracellular and extra-cellular pH values were monitored simultaneously. Upon glucose addition, anaerobic E. coli cells rapidly produce acids and develop a transmembrane pH gradient (delta pH). Glycolysis rates were calculated from the changes in the external pH. It was found that glycolysis rates are strongly dependent on internal pH, sharply decreasing when the pH drops below approximately 7.2. The ATPase inhibitor, dicyclohexylcarbodiimide (DCCD), prevented NTP hydrolysis and inhibited delta pH formation. The uncoupler, carbonyl cyanide p-triflouromethoxyphenyl hydrazone (FCCP), drastically reduced both the delta pH and the NTP level. When the cells were previously treated with DCCD, FCCP collapsed the delta pH while the NTP levels remained high. It is concluded that ATP produced by glycolysis is hydrolyzed by the membrane ATPase to generate a delta pH and that FCCP stimulates ATP hydrolysis by ATPase and collapses the proton gradient."}
{"id": "PMID:27786", "title": "Selective labeling of alpha-adrenergic receptors in caudate nucleus by [3H] dihydroergocryptine in the presence of spiperone-blocked dopamine receptors.", "content": "Because it was known that [(3)H]dihydroergocryptine can label alpha-adrenergic receptors as well as dopamine receptors, this study was done to establish the conditions under which [(3)H]dihydroergocryptine would be a reliable ligand for selective labeling of alpha-adrenergic receptors. The calf caudate was chosen because it contains both dopamine and adrenergic receptors, and 5 nM spiperone (spiroperidol) was used to block the neuroleptic/dopamine receptors. Thus, in the presence of spiperone, [(3)H]dihydroergocryptine exhibited saturable binding with a K(d) of 0.73 nM and a total number of sites of 150 fmol/mg of protein. The catechol neurotransmitters competed for [(3)H]dihydroergocryptine binding in the potencies order epinephrine > (-)-norepinephrine > dopamine, indicating that [(3)H]dihydroergocryptine (in the presence of 5 nM spiperone) was revealing alpha receptors. The alpha-adrenergic antagonists also competed for binding in the appropriate order: phentolamine > phenoxybenzamine > dibenamine. Finally, chlorpromazine was more potent than haloperidol in competing for [(3)H]dihydroergocryptine, also in accord with the properties of alpha receptors. These results with [(3)H]dihydroergocryptine as an alpha-adrenergic receptor ligand correlate well with those published by others for [(3)H]WB-4101.", "contents": "Selective labeling of alpha-adrenergic receptors in caudate nucleus by [3H] dihydroergocryptine in the presence of spiperone-blocked dopamine receptors. Because it was known that [(3)H]dihydroergocryptine can label alpha-adrenergic receptors as well as dopamine receptors, this study was done to establish the conditions under which [(3)H]dihydroergocryptine would be a reliable ligand for selective labeling of alpha-adrenergic receptors. The calf caudate was chosen because it contains both dopamine and adrenergic receptors, and 5 nM spiperone (spiroperidol) was used to block the neuroleptic/dopamine receptors. Thus, in the presence of spiperone, [(3)H]dihydroergocryptine exhibited saturable binding with a K(d) of 0.73 nM and a total number of sites of 150 fmol/mg of protein. The catechol neurotransmitters competed for [(3)H]dihydroergocryptine binding in the potencies order epinephrine > (-)-norepinephrine > dopamine, indicating that [(3)H]dihydroergocryptine (in the presence of 5 nM spiperone) was revealing alpha receptors. The alpha-adrenergic antagonists also competed for binding in the appropriate order: phentolamine > phenoxybenzamine > dibenamine. Finally, chlorpromazine was more potent than haloperidol in competing for [(3)H]dihydroergocryptine, also in accord with the properties of alpha receptors. These results with [(3)H]dihydroergocryptine as an alpha-adrenergic receptor ligand correlate well with those published by others for [(3)H]WB-4101."}
{"id": "PMID:27787", "title": "Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease.", "content": "Biochemical investigations were performed on autopsy tissues obtained from an 11-year-old girl who died with the juvenile, subacute neuropathic form of Gaucher disease. In addition to the expected deficiency of glucocerebrosidase activity, extracts of both liver and kidney from this individual displayed a profound (greater than or equal to 90%) deficiency of \"soluble\" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities. Fibroblasts obtained from this individual also contained markedly reduced levels of beta-xylosidase activity but normal levels of beta-D-fucosidase and beta-galactosidase activity. Because the soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed on a gel filtration column of Sephadex G-200, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of multiple glycosidase deficiencies in addition to the deficiency of glucocerebrosidase in a case of subacute neuropathic Gaucher disease suggests that other biochemical aberrations, in addition to a deficiency of glucocerebrosidase, might contribute to pathology in some cases of Gaucher disease.", "contents": "Multiple glycosidase deficiencies in a case of juvenile (type 3) Gaucher disease. Biochemical investigations were performed on autopsy tissues obtained from an 11-year-old girl who died with the juvenile, subacute neuropathic form of Gaucher disease. In addition to the expected deficiency of glucocerebrosidase activity, extracts of both liver and kidney from this individual displayed a profound (greater than or equal to 90%) deficiency of \"soluble\" beta-glucosidase, beta-xylosidase, and beta-galactosidase activities. Fibroblasts obtained from this individual also contained markedly reduced levels of beta-xylosidase activity but normal levels of beta-D-fucosidase and beta-galactosidase activity. Because the soluble beta-glucosidase, beta-xylosidase, and a portion of the beta-galactosidase activities from control human liver all cochromatographed on a gel filtration column of Sephadex G-200, it is suggested that these activities all reside in a single enzyme, analogous to the situation described in a number of nonhuman, mammalian tissues. This demonstration of multiple glycosidase deficiencies in addition to the deficiency of glucocerebrosidase in a case of subacute neuropathic Gaucher disease suggests that other biochemical aberrations, in addition to a deficiency of glucocerebrosidase, might contribute to pathology in some cases of Gaucher disease."}
{"id": "PMID:27788", "title": "Reduction of membrane potential, an immediate effect of colicin K.", "content": "Colicin K causes a rapid and drastic reduction of the membrane potential of Escherichia coli cells, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium. The colicin causes no major changes in the pH gradient, as measured by the uptake of butyric acid. The decrease in membrane potential following addition of colicin K to the cells is a prompt response that parallels or precedes known physiological effects such as efflux of accumulated substrates. Hence the loss of membrane potential qualifies as the primary action by which the colicin uncouples membrane-associated function from respiration. Certain peculiarities of bacterial cells pretreated with EDTA in their response to uncoupling agents and lipophilic ions are described.", "contents": "Reduction of membrane potential, an immediate effect of colicin K. Colicin K causes a rapid and drastic reduction of the membrane potential of Escherichia coli cells, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium. The colicin causes no major changes in the pH gradient, as measured by the uptake of butyric acid. The decrease in membrane potential following addition of colicin K to the cells is a prompt response that parallels or precedes known physiological effects such as efflux of accumulated substrates. Hence the loss of membrane potential qualifies as the primary action by which the colicin uncouples membrane-associated function from respiration. Certain peculiarities of bacterial cells pretreated with EDTA in their response to uncoupling agents and lipophilic ions are described."}
{"id": "PMID:27820", "title": "Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats.", "content": "The levels of serotonin (5-HT), 5-hydroxyindoleacetic acid, tyrosine (TYR), norepinephrine (NE), acetylcholine, GABA, glutamate (GLU), aspartate (ASP), alanine, glycine (GLY) and taurine were measured in the CNS of adult male rats selectively inbred to the F8 generation for alcohol preference (P) and non-preference (NP). With respect to the values found in the NP group, higher levels of 5-HT, GABA, GLU and GLY and lower levels of ASP were found in the diencephalon-mesencephalon (D-M) and higher levels of NE were found in the telencephalon (TEL) of the P group. The animals in the P and NP strains were further subdivided into two additional groups, one given only H2O (W) and the second given 10% ethanol (A) during a one week period, thereby producing four groups (NP-W, NP-A, P-W and P-A). With these conditions, the level of (a) TYR in the D-M was higher in the P-A and NP-A animals than in the P-W and NP-W groups respectively; (b) 5-HT in the TEL was higher in the NP-A group than NP-W group; and (c) GABA in the TEL was higher in the P-A than P-W animals. No differences were observed in the cerebellum between the two strains or between the subgroups within each strain. The present study also demonstrated that the P animals will work in an operant situation to obtain 10% ethanol, even when H2O is freely available, and will voluntarily bar-press up to 6-7 times for each ethanol reinforcement.", "contents": "Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats. The levels of serotonin (5-HT), 5-hydroxyindoleacetic acid, tyrosine (TYR), norepinephrine (NE), acetylcholine, GABA, glutamate (GLU), aspartate (ASP), alanine, glycine (GLY) and taurine were measured in the CNS of adult male rats selectively inbred to the F8 generation for alcohol preference (P) and non-preference (NP). With respect to the values found in the NP group, higher levels of 5-HT, GABA, GLU and GLY and lower levels of ASP were found in the diencephalon-mesencephalon (D-M) and higher levels of NE were found in the telencephalon (TEL) of the P group. The animals in the P and NP strains were further subdivided into two additional groups, one given only H2O (W) and the second given 10% ethanol (A) during a one week period, thereby producing four groups (NP-W, NP-A, P-W and P-A). With these conditions, the level of (a) TYR in the D-M was higher in the P-A and NP-A animals than in the P-W and NP-W groups respectively; (b) 5-HT in the TEL was higher in the NP-A group than NP-W group; and (c) GABA in the TEL was higher in the P-A than P-W animals. No differences were observed in the cerebellum between the two strains or between the subgroups within each strain. The present study also demonstrated that the P animals will work in an operant situation to obtain 10% ethanol, even when H2O is freely available, and will voluntarily bar-press up to 6-7 times for each ethanol reinforcement."}
{"id": "PMID:27827", "title": "[Anxiety- an approach to defining terms and formulating a methodological concept for measuring anxiety states within the framework of clinical trials with anxiolytic substances (author's transl)].", "content": "A methodological concept for measuring anxiety states and changes in anxiety states in clinical studies with anxiolytic substances is presented: Effectivity should be evaluated on several levels which include emotions, objects of anxiety, psychophysiology, biochemistry, and observed behavior. This test concept is based on new knowledge from behavior psychology, learning theory, psychology of testing, psychophysiology, biochemistry, neuroendocrinology, and psychiatry. In diagrams, important mechanisms of thr origin of experimental, stress-induced and pathological anxiety states are depicted. The point is stressed that anxiety is situational and fluctuates.", "contents": "[Anxiety- an approach to defining terms and formulating a methodological concept for measuring anxiety states within the framework of clinical trials with anxiolytic substances (author's transl)]. A methodological concept for measuring anxiety states and changes in anxiety states in clinical studies with anxiolytic substances is presented: Effectivity should be evaluated on several levels which include emotions, objects of anxiety, psychophysiology, biochemistry, and observed behavior. This test concept is based on new knowledge from behavior psychology, learning theory, psychology of testing, psychophysiology, biochemistry, neuroendocrinology, and psychiatry. In diagrams, important mechanisms of thr origin of experimental, stress-induced and pathological anxiety states are depicted. The point is stressed that anxiety is situational and fluctuates."}
{"id": "PMID:27823", "title": "Determination of mepyramine, aminophenazone, nialamide and chloroquine using the deltapj method.", "content": "Mepyramine maleate, aminophenazone, nialamide and chloroquine phosphate are examples of compounds which do not fulfil the requirements of the delta A method. By the proper choice of polynomial and wavelengths, the deltapj method has been successfully applied to their determination. The mean percentage recoveries were found to be 100.2 +/- 0.8, 99.6 +/- 0.6, 99.1 +/- 1.7 and 100.4 +/- 1.3, respectively.", "contents": "Determination of mepyramine, aminophenazone, nialamide and chloroquine using the deltapj method. Mepyramine maleate, aminophenazone, nialamide and chloroquine phosphate are examples of compounds which do not fulfil the requirements of the delta A method. By the proper choice of polynomial and wavelengths, the deltapj method has been successfully applied to their determination. The mean percentage recoveries were found to be 100.2 +/- 0.8, 99.6 +/- 0.6, 99.1 +/- 1.7 and 100.4 +/- 1.3, respectively."}
{"id": "PMID:27828", "title": "Autonomic perception and responses in anxiety-inducing situations.", "content": "The anxiolytic and sedative properties of a thienodiazepine (clotiazepam) were investigated in 40 healthy subjects with varying degrees of arousal and with the aid of specific anxiety-inducing conditions. A cross-over design with a double blind technique was used. EEG, heart and respiratory rate, peripheral pulse volume and skin resistance were measured during the anxiety-inducing conditions with the visualization of neutral and fearful situations as well as with the threat of shock. The mood, physical sensations and behaviour tendencies of the test subjects were determined by self-rating questionnaires. The anxiolytic and sedative effects of the thienodiazepine under study were able to be differentiated as far as subjective perception and autonomic responses were concerned. The development of sedative and anxiolytic effects is dependent on the subject's state of arousal. Situations involving the anticipation of anxiety are sufficient as proof of pharmacogenic anxiolysis. The tranquilizer reduces anxiety and physical tension, but does not influence the timing of autonomic readiness responses, and thus does not affect the coping strategies.", "contents": "Autonomic perception and responses in anxiety-inducing situations. The anxiolytic and sedative properties of a thienodiazepine (clotiazepam) were investigated in 40 healthy subjects with varying degrees of arousal and with the aid of specific anxiety-inducing conditions. A cross-over design with a double blind technique was used. EEG, heart and respiratory rate, peripheral pulse volume and skin resistance were measured during the anxiety-inducing conditions with the visualization of neutral and fearful situations as well as with the threat of shock. The mood, physical sensations and behaviour tendencies of the test subjects were determined by self-rating questionnaires. The anxiolytic and sedative effects of the thienodiazepine under study were able to be differentiated as far as subjective perception and autonomic responses were concerned. The development of sedative and anxiolytic effects is dependent on the subject's state of arousal. Situations involving the anticipation of anxiety are sufficient as proof of pharmacogenic anxiolysis. The tranquilizer reduces anxiety and physical tension, but does not influence the timing of autonomic readiness responses, and thus does not affect the coping strategies."}
{"id": "PMID:27829", "title": "[Treatment of pain with psychotropic drugs (author's transl)].", "content": "30 patients suffering from therapy-resistant chronic pain were divided into three groups according to drive and mood: I. psychomotor inhibition combined with depressive mood, II. agitation and depressive mood, III. agitation combined normal mood. The psychopharmacological treatment of pain showed sufficient results, when the drugs were directed to the target symptoms \"agitation\", \"lack of drive\", and \"depression\". The differentiated administration of activating or sedative antidepressants and neuroleptics caused reduction or absence of pain while the routine administration of neuroleptics (i.e. chlorpromazine) was less effective.", "contents": "[Treatment of pain with psychotropic drugs (author's transl)]. 30 patients suffering from therapy-resistant chronic pain were divided into three groups according to drive and mood: I. psychomotor inhibition combined with depressive mood, II. agitation and depressive mood, III. agitation combined normal mood. The psychopharmacological treatment of pain showed sufficient results, when the drugs were directed to the target symptoms \"agitation\", \"lack of drive\", and \"depression\". The differentiated administration of activating or sedative antidepressants and neuroleptics caused reduction or absence of pain while the routine administration of neuroleptics (i.e. chlorpromazine) was less effective."}
{"id": "PMID:27832", "title": "Early diagnosis of crepitant gangrene caused by Bacteroides melaninogenicus.", "content": "A rapid non-invasive test for the presence of B. melaninogenicus in the wounds of crepitant non-clostridial gangrene is described. The wounds are viewed under an ultraviolet light, and the presence of bright red fluorescene indicates the probable presence of B. melaninogenicus.", "contents": "Early diagnosis of crepitant gangrene caused by Bacteroides melaninogenicus. A rapid non-invasive test for the presence of B. melaninogenicus in the wounds of crepitant non-clostridial gangrene is described. The wounds are viewed under an ultraviolet light, and the presence of bright red fluorescene indicates the probable presence of B. melaninogenicus."}
{"id": "PMID:27830", "title": "The effects of TAB and of adrenergic blocking drugs on the course of the experimental irradiation disease.", "content": "The experiment is aimed at establishing the consequences of the endotoxic stress (TAB) associated with alpha- or beta-adrenergic selective blocking drugs on the course of the acute irradiation disease in rats (700R, gamma rad Co60). TAB administered before or after irradiation, alone or associated with propranolol, increases the surviving rate at 30 and 60 days from exposure as compared to the controls (LD 95/30 days). Generally, dibenzyline has unfavourable effects on mortality and survival rate at the mentioned intervals. Based on the data obtained, an adrenergic component is analysed in achieving the survival increase by TAB and beta-adrenergic blocking substances; a hypothesis about the mechanisms involved is advanced.", "contents": "The effects of TAB and of adrenergic blocking drugs on the course of the experimental irradiation disease. The experiment is aimed at establishing the consequences of the endotoxic stress (TAB) associated with alpha- or beta-adrenergic selective blocking drugs on the course of the acute irradiation disease in rats (700R, gamma rad Co60). TAB administered before or after irradiation, alone or associated with propranolol, increases the surviving rate at 30 and 60 days from exposure as compared to the controls (LD 95/30 days). Generally, dibenzyline has unfavourable effects on mortality and survival rate at the mentioned intervals. Based on the data obtained, an adrenergic component is analysed in achieving the survival increase by TAB and beta-adrenergic blocking substances; a hypothesis about the mechanisms involved is advanced."}
{"id": "PMID:27831", "title": "Some neural effects of adenosin.", "content": "The possible neural effects of adenosine were investigated by using electrophysiological techniques at the level of some central and peripheral synapses. The evoked potentials in the somatosensorial cerebral cortex are influenced according to both the type of administration and the level of the electrical stimulation. While the local application does not induce significant alterations, the intrathalamic injections and the perfusion of the IIIrd cerebral ventricle do change the distribution of activated units at the level of different cortical layers especially during the peripheral stimulation. The frequency of spontaneous miniature discharges intracellularly recorded in the neuromuscular junction (mepp) is significantly depressed by adenosine. This effect is calcium- and dose-dependent. The end plate potentials (EPP) were also depressed. The statistical binomial analysis of the phenomenon indicated that adenosine induces a decrease if the presynaptic pool of the available transmitter. The data obtained demonstrate a presynaptic inhibitory action of adenosine beside its known vascular and metaholic effects.", "contents": "Some neural effects of adenosin. The possible neural effects of adenosine were investigated by using electrophysiological techniques at the level of some central and peripheral synapses. The evoked potentials in the somatosensorial cerebral cortex are influenced according to both the type of administration and the level of the electrical stimulation. While the local application does not induce significant alterations, the intrathalamic injections and the perfusion of the IIIrd cerebral ventricle do change the distribution of activated units at the level of different cortical layers especially during the peripheral stimulation. The frequency of spontaneous miniature discharges intracellularly recorded in the neuromuscular junction (mepp) is significantly depressed by adenosine. This effect is calcium- and dose-dependent. The end plate potentials (EPP) were also depressed. The statistical binomial analysis of the phenomenon indicated that adenosine induces a decrease if the presynaptic pool of the available transmitter. The data obtained demonstrate a presynaptic inhibitory action of adenosine beside its known vascular and metaholic effects."}
{"id": "PMID:27835", "title": "Use of antianxiety agents in anxious outpatients.", "content": "The present paper reviews the role of antianxiety agents in the treatment of nonpsychotic anxious patients. Major emphasis is placed on findings from clinical trials conducted by this research group. Consideration is given to the relative efficacy of available antianxiety agents, to patients response in relation to patterns of symptomatology, and to the degree of symptom relief experienced by drug-treated anxious patients. Also discussed are some of the many nonspecific factors that affect improvement with drug treatment in general and with the benzodiazepines in particular. It is concluded that many anxious patients are not currently receiving adequate drug treatment, and may require longer periods of drug therapy or supplemental nondrug intervention.", "contents": "Use of antianxiety agents in anxious outpatients. The present paper reviews the role of antianxiety agents in the treatment of nonpsychotic anxious patients. Major emphasis is placed on findings from clinical trials conducted by this research group. Consideration is given to the relative efficacy of available antianxiety agents, to patients response in relation to patterns of symptomatology, and to the degree of symptom relief experienced by drug-treated anxious patients. Also discussed are some of the many nonspecific factors that affect improvement with drug treatment in general and with the benzodiazepines in particular. It is concluded that many anxious patients are not currently receiving adequate drug treatment, and may require longer periods of drug therapy or supplemental nondrug intervention."}
{"id": "PMID:27836", "title": "Neuropharmacological profile of clobazam, a new 1',5'-benzodiazepine.", "content": "The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam. Clobazam was half as potent as diazepam in depressing the amplitude of visual evoked potentials in the nonanaesthetized rabbit, whereas the depressing effect on spinal polysynaptic reflexes in the decerebrated cat was only 1/7 --1/30 of the diazepam effect. The action of clobazam and diazepam on VEP also showed differences in time course, i.e., the peak effect of clobazam lasted from 1 to 6 h after application, whereas the effect of diazepam appeared after 10 min and declined already after 1 h. Both compounds had similar effects on computer-analyzed spontaneous EEG in the rabbit (power spectrum analysis), with an increase of power in the beta-band (13-39Hz) and a decrease in the alpha (8-13 Hz) and theta (4-8Hz) bands.", "contents": "Neuropharmacological profile of clobazam, a new 1',5'-benzodiazepine. The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam. Clobazam was half as potent as diazepam in depressing the amplitude of visual evoked potentials in the nonanaesthetized rabbit, whereas the depressing effect on spinal polysynaptic reflexes in the decerebrated cat was only 1/7 --1/30 of the diazepam effect. The action of clobazam and diazepam on VEP also showed differences in time course, i.e., the peak effect of clobazam lasted from 1 to 6 h after application, whereas the effect of diazepam appeared after 10 min and declined already after 1 h. Both compounds had similar effects on computer-analyzed spontaneous EEG in the rabbit (power spectrum analysis), with an increase of power in the beta-band (13-39Hz) and a decrease in the alpha (8-13 Hz) and theta (4-8Hz) bands."}
{"id": "PMID:27846", "title": "Studies on cholesterol esterification in human tissues.", "content": "In vitro cholesteryl synthesis from oleic acid [1-14C] was studied with enzyme preparations from human thoracic aorta and liver. Results from studies on the properties of the esterifying system provide good evidence that the mechanism involves fatty acyl-CoA-cholesterol acyl transferase. In studies on human thoracic aorta with varying degrees of atherosclerotic disease, and pairs of normal and diseased aorta from the same subject, there was no obvious relationship between aortic cholesteryl esterifying activity and severity of atheroma. Normal aorta from two young males, presumably free of atherosclerosis, had relatively very low esterifying activity. In the six liver samples tested, there was negligible esterifying activity, in contrast to the high activity seen in the case of rat liver. For the thin layer chromatographic isolation of the labeled cholesteryl oleate a solvent system of isooctane:diethyl ether (100:6) was found to give a better separation of the ester than the petroleum ether: diethylether:acetic acid system generally used.", "contents": "Studies on cholesterol esterification in human tissues. In vitro cholesteryl synthesis from oleic acid [1-14C] was studied with enzyme preparations from human thoracic aorta and liver. Results from studies on the properties of the esterifying system provide good evidence that the mechanism involves fatty acyl-CoA-cholesterol acyl transferase. In studies on human thoracic aorta with varying degrees of atherosclerotic disease, and pairs of normal and diseased aorta from the same subject, there was no obvious relationship between aortic cholesteryl esterifying activity and severity of atheroma. Normal aorta from two young males, presumably free of atherosclerosis, had relatively very low esterifying activity. In the six liver samples tested, there was negligible esterifying activity, in contrast to the high activity seen in the case of rat liver. For the thin layer chromatographic isolation of the labeled cholesteryl oleate a solvent system of isooctane:diethyl ether (100:6) was found to give a better separation of the ester than the petroleum ether: diethylether:acetic acid system generally used."}
{"id": "PMID:27847", "title": "Inhibition of acute anaphylaxis in the chicken by anti-allergic drugs.", "content": "The anti-anaphylactic effects of four potential anti-allergic agents (DSCG: disodium cromoglycate, PRD-92-EA, M&B 22,948 and DECC: diethylcarbamazine citrate) were studied on cardiovascular responses of acute systemic anaphylaxis and chemical mediators of immediate hypersensitivity in chickens. Compounds M&B 22,948, PRD-92-EA, DSCG and DECC all inhibited cardiovascular manifestations of systemic anaphylaxis in domestic fowl. High doses of Compounds PRD-92 EA, M&B 22,948 and DECC also exhibited a nonspecific receptor blocking activity towards exogenously administered chemical mediators of anaphylaxis.", "contents": "Inhibition of acute anaphylaxis in the chicken by anti-allergic drugs. The anti-anaphylactic effects of four potential anti-allergic agents (DSCG: disodium cromoglycate, PRD-92-EA, M&B 22,948 and DECC: diethylcarbamazine citrate) were studied on cardiovascular responses of acute systemic anaphylaxis and chemical mediators of immediate hypersensitivity in chickens. Compounds M&B 22,948, PRD-92-EA, DSCG and DECC all inhibited cardiovascular manifestations of systemic anaphylaxis in domestic fowl. High doses of Compounds PRD-92 EA, M&B 22,948 and DECC also exhibited a nonspecific receptor blocking activity towards exogenously administered chemical mediators of anaphylaxis."}
{"id": "PMID:27848", "title": "Comparison of the mechanisms controlling intracellular pH and sodium in snail neurones.", "content": "Ion-sensitive microelectrodes were used to record intracellular pH, Na+ and Cl- in snail neurones. NaCl or HCl was injected iontophoretically to compare the Na pump with the pHi regulating system. The Na pump was inhibited by ouabain, carbonyl cyanide m-chlorophenyl hydrazone and increasing the membrane potential, whereas the pHi regulating system was relatively unaffected. Activation of the Na pump had no effect on pHi whereas activation of the pHi recovery process increased internal Na+. Activation of the pHi recovery process by CO2 application increased internal Na+ and also decreased internal Cl-. The results show that there is no direct connexion between the Na pump and the pHi recovery process, and that the pHi recovery process is electroneutral, and appears not to require metabolic energy. The results also confirm that the pHi recovery process involves the influx of Na+ ions and the efflux of Cl- ions.", "contents": "Comparison of the mechanisms controlling intracellular pH and sodium in snail neurones. Ion-sensitive microelectrodes were used to record intracellular pH, Na+ and Cl- in snail neurones. NaCl or HCl was injected iontophoretically to compare the Na pump with the pHi regulating system. The Na pump was inhibited by ouabain, carbonyl cyanide m-chlorophenyl hydrazone and increasing the membrane potential, whereas the pHi regulating system was relatively unaffected. Activation of the Na pump had no effect on pHi whereas activation of the pHi recovery process increased internal Na+. Activation of the pHi recovery process by CO2 application increased internal Na+ and also decreased internal Cl-. The results show that there is no direct connexion between the Na pump and the pHi recovery process, and that the pHi recovery process is electroneutral, and appears not to require metabolic energy. The results also confirm that the pHi recovery process involves the influx of Na+ ions and the efflux of Cl- ions."}
{"id": "PMID:27849", "title": "Intracellular acid-base state at a variable temperature in air-breathing vertebrates and its representation.", "content": "When temperature changes are superimposed on changes in the control variables of acid-base state (PCO2, strong ion difference), the understanding of acid-base changes becomes difficult. A solution has recently been proposed for blood (Malan, 1977); it was based on the assumption that closed system conditions correspond to a minimal change in the overall acid-base state when temperature varies. The feasibility of extending these concepts to muscle intracellular acid-base vs temperature relationships is evaluated on the basis of a model study; the errors made by replacing closed conditions (which require knowledge of chemical composition) by more convenient approximations are estimated. A representation of both extracellular and intracellular acid-base data on a temperature-corrected bicarbonate-pH diagram is derived. It allows the interpretation of variable-temperature intracellular acid-base changes in terms of changes in control variables, 'respiratory (PCO2) or 'metabolic' (strong ion difference).", "contents": "Intracellular acid-base state at a variable temperature in air-breathing vertebrates and its representation. When temperature changes are superimposed on changes in the control variables of acid-base state (PCO2, strong ion difference), the understanding of acid-base changes becomes difficult. A solution has recently been proposed for blood (Malan, 1977); it was based on the assumption that closed system conditions correspond to a minimal change in the overall acid-base state when temperature varies. The feasibility of extending these concepts to muscle intracellular acid-base vs temperature relationships is evaluated on the basis of a model study; the errors made by replacing closed conditions (which require knowledge of chemical composition) by more convenient approximations are estimated. A representation of both extracellular and intracellular acid-base data on a temperature-corrected bicarbonate-pH diagram is derived. It allows the interpretation of variable-temperature intracellular acid-base changes in terms of changes in control variables, 'respiratory (PCO2) or 'metabolic' (strong ion difference)."}
{"id": "PMID:27850", "title": "Regulation of blood pH in teleost fish.", "content": "The nature of pH changes with temperature is similar in both air-breathing and water-breathing poikilotherms having a pH-temperature slope of -0.015 to 0.020 U/degrees C. The means by which this is accomplished are quite different in the two groups. The air-breather behaves in vivo as a Rosenthal, or constant CO2 content system, with PaCO2 increasing at higher temperatures. The increase in PaCO2 is brought about by a reduction in the ration VE/MCO2. The water-breather, on the other hand, does not change VG/MO2, so as not to sacrifice oxygen delivery, and consequently does not control PaCO2 by ventilation and perhaps does not control it at all. Instead, the ratio of CT/SCO2 is controlled by altering blood bicarbonate concentration. Since alteraction of Na+ and Cl- uptake rates affects blood pH, and alterations of blood pH affect uptake of Na+ and Cl- at the gills, the carrier-mediated Na+/H+(NH4+) and Cl-/HCO3-(OH-) mechanisms now known to occur in gills appear to be the primary pH-regulating mechanism in water-breathers. Our knowledge of the role of gut and kidney in pH regulation is incomplete, but on the basis of preliminary information the kidney does not appear to respond to acid challenge.", "contents": "Regulation of blood pH in teleost fish. The nature of pH changes with temperature is similar in both air-breathing and water-breathing poikilotherms having a pH-temperature slope of -0.015 to 0.020 U/degrees C. The means by which this is accomplished are quite different in the two groups. The air-breather behaves in vivo as a Rosenthal, or constant CO2 content system, with PaCO2 increasing at higher temperatures. The increase in PaCO2 is brought about by a reduction in the ration VE/MCO2. The water-breather, on the other hand, does not change VG/MO2, so as not to sacrifice oxygen delivery, and consequently does not control PaCO2 by ventilation and perhaps does not control it at all. Instead, the ratio of CT/SCO2 is controlled by altering blood bicarbonate concentration. Since alteraction of Na+ and Cl- uptake rates affects blood pH, and alterations of blood pH affect uptake of Na+ and Cl- at the gills, the carrier-mediated Na+/H+(NH4+) and Cl-/HCO3-(OH-) mechanisms now known to occur in gills appear to be the primary pH-regulating mechanism in water-breathers. Our knowledge of the role of gut and kidney in pH regulation is incomplete, but on the basis of preliminary information the kidney does not appear to respond to acid challenge."}
{"id": "PMID:27851", "title": "Weak acids, weak bases and intracellular pH.", "content": "Against the background of classical observations made 50 years ago, a brief review is offered of some of the work performed in the author's laboratory on the behavior of weak acids and bases towards living animal cells. The significance of membrane permeability of the charged partner of these electrolytes is pointed out, and the existence of an active process of H+ extrusion (or its equivalent) in response to acid loading is demonstrated. The effect of intracellular inhomogeneity on weak acid and base transmembrane distribution is examined. The significance of these variables for weak acid- or base-derived intracellular pH is discussed.", "contents": "Weak acids, weak bases and intracellular pH. Against the background of classical observations made 50 years ago, a brief review is offered of some of the work performed in the author's laboratory on the behavior of weak acids and bases towards living animal cells. The significance of membrane permeability of the charged partner of these electrolytes is pointed out, and the existence of an active process of H+ extrusion (or its equivalent) in response to acid loading is demonstrated. The effect of intracellular inhomogeneity on weak acid and base transmembrane distribution is examined. The significance of these variables for weak acid- or base-derived intracellular pH is discussed."}
{"id": "PMID:27852", "title": "Evaluation of the DMO method for measuring intracellular pH.", "content": "Intracellular pH in single muscle fibres from Balanus nubilus was determined, both by the weak acid distribution method (using 5,5-dimethyl-2,4-oxazolidine dione) and by means of a glass pH microelectrode, following prolonged equilibrations in normal, acid or alkaline Ringer solutions. In the DMO method [3H]inulin was combined with [14C]DMO so that an extracellular space could be calculated for each 'DMO space' on each fibre. Less than ideal uptake curves were obtained both for [14C]DMO and [3H]inulin, yet the calculated pHi compared favourably with the microelectrode pHi, especially when the DMO-pHi was calculated from [14C]DMO and [3H]inulin values obtained by extrapolating the 'plateaus' of the uptake curves to time zero. The Waddell and Butler equation was examined to determine why acceptable pHi values should be forthcoming from less than ideal uptake data.", "contents": "Evaluation of the DMO method for measuring intracellular pH. Intracellular pH in single muscle fibres from Balanus nubilus was determined, both by the weak acid distribution method (using 5,5-dimethyl-2,4-oxazolidine dione) and by means of a glass pH microelectrode, following prolonged equilibrations in normal, acid or alkaline Ringer solutions. In the DMO method [3H]inulin was combined with [14C]DMO so that an extracellular space could be calculated for each 'DMO space' on each fibre. Less than ideal uptake curves were obtained both for [14C]DMO and [3H]inulin, yet the calculated pHi compared favourably with the microelectrode pHi, especially when the DMO-pHi was calculated from [14C]DMO and [3H]inulin values obtained by extrapolating the 'plateaus' of the uptake curves to time zero. The Waddell and Butler equation was examined to determine why acceptable pHi values should be forthcoming from less than ideal uptake data."}
{"id": "PMID:27853", "title": "Intracellular pH transients induced by Co2 or NH3.", "content": "Experiments are reviewed in which intracellular pH (pHi), during exposure of a cell to CO2- or NH3-containing solutions, not only undergoes an acidification of alkalinization, respectively, but tends to return toward its original value and, upon removal of the test solution, rebounds to a value more alkaline or acid, respectively, than the initial one. A simple physiochemical model is discussed which interprets these observations both qualitatively and quantitatively. In the case of NH3-induced transients, only passive movements seem to take place; in the CO2-induced transients one must postulate an active 'proton pump'. Experimentally verifiable predictions can be made from these models. It is suggested that many physiological effects follow exposure to CO2 or NH3 may be subject to similar transients and rebounds.", "contents": "Intracellular pH transients induced by Co2 or NH3. Experiments are reviewed in which intracellular pH (pHi), during exposure of a cell to CO2- or NH3-containing solutions, not only undergoes an acidification of alkalinization, respectively, but tends to return toward its original value and, upon removal of the test solution, rebounds to a value more alkaline or acid, respectively, than the initial one. A simple physiochemical model is discussed which interprets these observations both qualitatively and quantitatively. In the case of NH3-induced transients, only passive movements seem to take place; in the CO2-induced transients one must postulate an active 'proton pump'. Experimentally verifiable predictions can be made from these models. It is suggested that many physiological effects follow exposure to CO2 or NH3 may be subject to similar transients and rebounds."}
{"id": "PMID:27854", "title": "Intracellular buffering.", "content": "In the quantification of buffering the distinct roles of bicarbonate and of other buffers must be taken into account. The determination of the total non-bicarbonate buffer value, betaa, in intact tissues is complicated by active pH regulation and by heterogeneity of cytoplasm with respect to betaa, while heterogeneity with respect to pH in vivo could cause errors in estimates made with homogenates. Available estimates of betaa are discussed, as are the individual contributions of proteins, dipeptides and phosphates. A high betaa is appropriate in cells which sometimes have high rates of glycolysis, or which buffer extracellular fluid, but non-protein buffer concentrations can be well below the limits imposed by osmolarity, perhaps because buffering can upset ionic gradients.", "contents": "Intracellular buffering. In the quantification of buffering the distinct roles of bicarbonate and of other buffers must be taken into account. The determination of the total non-bicarbonate buffer value, betaa, in intact tissues is complicated by active pH regulation and by heterogeneity of cytoplasm with respect to betaa, while heterogeneity with respect to pH in vivo could cause errors in estimates made with homogenates. Available estimates of betaa are discussed, as are the individual contributions of proteins, dipeptides and phosphates. A high betaa is appropriate in cells which sometimes have high rates of glycolysis, or which buffer extracellular fluid, but non-protein buffer concentrations can be well below the limits imposed by osmolarity, perhaps because buffering can upset ionic gradients."}
{"id": "PMID:27855", "title": "Active control of intracellular pH.", "content": "When the interior of a squid giant axon is loaded with acid, the cell responds by extruding that acid in an energy-requiring process. Our results indicate that this acid extrusion is accomplished by exchanging external HCO3- for internal Cl- at the expense of ATP.", "contents": "Active control of intracellular pH. When the interior of a squid giant axon is loaded with acid, the cell responds by extruding that acid in an energy-requiring process. Our results indicate that this acid extrusion is accomplished by exchanging external HCO3- for internal Cl- at the expense of ATP."}
{"id": "PMID:27856", "title": "Measurement of intracellular pH and aspects of its control in higher plant cells cultivated in liquid medium.", "content": "The 5,5-dimethyloxazolidine-2,4-dione (DMO) method for the determination of intracellular pH has been adapted to Acer pseudoplatanus cells cultivated in liquid medium. DMO is metabolized by these cells and this parameter has to be taken into account in the measurement of the intracellular concentration of free DMO. As the cells contain a large acidic vacuolar compartment, the intracellular pH estimated from the DMO technique is an overall pHi', the dependence of which on various cytoplasmic and vacuolar characteristics has been discussed. Important modifications of these overall pHi values under the influence of CO2 or NH4+ have been measured. These pHi modifications strongly affect the regulation of cell division through the control of the intracellular concentration of hormones of the auxin type.", "contents": "Measurement of intracellular pH and aspects of its control in higher plant cells cultivated in liquid medium. The 5,5-dimethyloxazolidine-2,4-dione (DMO) method for the determination of intracellular pH has been adapted to Acer pseudoplatanus cells cultivated in liquid medium. DMO is metabolized by these cells and this parameter has to be taken into account in the measurement of the intracellular concentration of free DMO. As the cells contain a large acidic vacuolar compartment, the intracellular pH estimated from the DMO technique is an overall pHi', the dependence of which on various cytoplasmic and vacuolar characteristics has been discussed. Important modifications of these overall pHi values under the influence of CO2 or NH4+ have been measured. These pHi modifications strongly affect the regulation of cell division through the control of the intracellular concentration of hormones of the auxin type."}
{"id": "PMID:27857", "title": "Independent and dependent variables of acid-base control.", "content": "Basic physical principles and concepts plus computer-implemented numberical techniques now make possible a thorough quantitative analysis of acid-base systems. Some important conclusions from that analysis are presented: 1. Acid-base balance for physiological solutions hould be defined as the value of [OH-]/[H+]. 2. pH is a dangerously misleading indirect representation of [H+]. 3. Strong electrolytes affect [H+] and other deendent acid-base variables primarily through their resultant, the strong ion difference. 4 Hydrogen ion concentration in biological solutions is determined by the strong ion difference, the carbon dioxide partial pressure, and the total weak acid present. Changes in hydrogen ion concentration can be broght about only by changing one or more of these three independent variables. The same statements apply to all the other dependent variables, notably bicarbonate ion concentration. None of the dependent variables determines any other dependent variable, although their quantitative behaviors are necessarily correlected. 5. Solutions separated by membranes can interact in acid-base terms only by processes which alter the values of their independent variables. Interaction of intra- and extracellular acid-base balance can only occur by the cell membrane altering these independent variables in the extracellular fluid and in the cytosol.", "contents": "Independent and dependent variables of acid-base control. Basic physical principles and concepts plus computer-implemented numberical techniques now make possible a thorough quantitative analysis of acid-base systems. Some important conclusions from that analysis are presented: 1. Acid-base balance for physiological solutions hould be defined as the value of [OH-]/[H+]. 2. pH is a dangerously misleading indirect representation of [H+]. 3. Strong electrolytes affect [H+] and other deendent acid-base variables primarily through their resultant, the strong ion difference. 4 Hydrogen ion concentration in biological solutions is determined by the strong ion difference, the carbon dioxide partial pressure, and the total weak acid present. Changes in hydrogen ion concentration can be broght about only by changing one or more of these three independent variables. The same statements apply to all the other dependent variables, notably bicarbonate ion concentration. None of the dependent variables determines any other dependent variable, although their quantitative behaviors are necessarily correlected. 5. Solutions separated by membranes can interact in acid-base terms only by processes which alter the values of their independent variables. Interaction of intra- and extracellular acid-base balance can only occur by the cell membrane altering these independent variables in the extracellular fluid and in the cytosol."}
{"id": "PMID:27860", "title": "[Pathological and compensatory processes in the cerebral circulation during blood transfusion shock].", "content": "In experiments on dogs the intravenous injection of heterogenous blood resulted in a decrease of total arterial pressure, weakening of the brain blood flow, fall of Po2 and pH in the brain cortex. A simultaneous constriction if inner carotid arteries is depending on direct action on the vascular wall of heterogenous proteins and on a release in it of physiologically active substances, such as serotonin. Fine pial arteries were dilated by the compensatory mechanism that was not associated with a decrease of intravascular and with direct action of hypoxia or acid metabolites on vascular walls. It was proposed that the trigger mechanism of this vasodilatation is hypoxic changes of metabolism in the nervous tissue.", "contents": "[Pathological and compensatory processes in the cerebral circulation during blood transfusion shock]. In experiments on dogs the intravenous injection of heterogenous blood resulted in a decrease of total arterial pressure, weakening of the brain blood flow, fall of Po2 and pH in the brain cortex. A simultaneous constriction if inner carotid arteries is depending on direct action on the vascular wall of heterogenous proteins and on a release in it of physiologically active substances, such as serotonin. Fine pial arteries were dilated by the compensatory mechanism that was not associated with a decrease of intravascular and with direct action of hypoxia or acid metabolites on vascular walls. It was proposed that the trigger mechanism of this vasodilatation is hypoxic changes of metabolism in the nervous tissue."}
{"id": "PMID:27862", "title": "[Gastric secretion and gastrin values following portocaval and splenocaval shunts in the rat].", "content": "The basal and gastrin-stimulated gastric acid output was measured in rats with a distal splenocaval shunt. In addition, serum gastrin levels were determined in rats with splenocaval and portacaval shunts. The rise in gastric acid output with increasing gastrin dosage was the same in rats with splenocaval shunt as in the controls. Serum gastrin levels were not influenced by portocaval or splenocaval shunting.", "contents": "[Gastric secretion and gastrin values following portocaval and splenocaval shunts in the rat]. The basal and gastrin-stimulated gastric acid output was measured in rats with a distal splenocaval shunt. In addition, serum gastrin levels were determined in rats with splenocaval and portacaval shunts. The rise in gastric acid output with increasing gastrin dosage was the same in rats with splenocaval shunt as in the controls. Serum gastrin levels were not influenced by portocaval or splenocaval shunting."}
{"id": "PMID:27863", "title": "[Preventive practice in dentistry and its current meaning].", "content": "Improvements in the field of sealants and of adhesive restorations based thereon represent the most important new development in preventive dentistry. Caries prevention by means of better nutritional habits is greatly enhanced by newly developed and marketed sugar-free and tooth sparing products. Statistical mortality studies have again demonstrated that prevention by means of fluorides constitutes no danger to public health. Considerable advances have been made in the field of fluoridation of domestic salt. Newer Scandinavian studies revealed that intensive care programs with children including dental hygiene sessions every 3-5 weeks resulted in moderate decreases of caries incidence. By contrast, intensive care programs with adults were extremely successful. By means of 4-6 recall sessions with dental hygienists it was possible to completely stop periodontal destruction for 4, even for 7 years. Apart from initial restorative and conservative dental work, the success of periodontal treatment may be guaranteed only by prevention of recurring gingivitis. Extensive dental statistics from Switzerland reveal a marked success of applied preventive dental medicine. The work of dental practitioners is by now greatly influenced by the new scientific insight gained from research in the prevention of dental disease.", "contents": "[Preventive practice in dentistry and its current meaning]. Improvements in the field of sealants and of adhesive restorations based thereon represent the most important new development in preventive dentistry. Caries prevention by means of better nutritional habits is greatly enhanced by newly developed and marketed sugar-free and tooth sparing products. Statistical mortality studies have again demonstrated that prevention by means of fluorides constitutes no danger to public health. Considerable advances have been made in the field of fluoridation of domestic salt. Newer Scandinavian studies revealed that intensive care programs with children including dental hygiene sessions every 3-5 weeks resulted in moderate decreases of caries incidence. By contrast, intensive care programs with adults were extremely successful. By means of 4-6 recall sessions with dental hygienists it was possible to completely stop periodontal destruction for 4, even for 7 years. Apart from initial restorative and conservative dental work, the success of periodontal treatment may be guaranteed only by prevention of recurring gingivitis. Extensive dental statistics from Switzerland reveal a marked success of applied preventive dental medicine. The work of dental practitioners is by now greatly influenced by the new scientific insight gained from research in the prevention of dental disease."}
{"id": "PMID:27864", "title": "Lymphocyte ecto-5'-nucleotidase deficiency in agammaglobulinemia.", "content": "Fresh peripheral blood lymphocytes from eight patients with congenital agammaglobulinemia demonstrate reduced ecto-5'-nucleotidase activity when compared to the mean activity of normal subjects and patients with other forms of immunoglobulin deficiency. A specific defect of ecto-5'-nucleotidase is further suggested by normal values for lymphocyte ecto-adenosinetriphosphatase and ecto-nonspecific phosphatase. The data provide evidence for an enzyme deficiency in this X-linked, B lymphocyte deficiency syndrome.", "contents": "Lymphocyte ecto-5'-nucleotidase deficiency in agammaglobulinemia. Fresh peripheral blood lymphocytes from eight patients with congenital agammaglobulinemia demonstrate reduced ecto-5'-nucleotidase activity when compared to the mean activity of normal subjects and patients with other forms of immunoglobulin deficiency. A specific defect of ecto-5'-nucleotidase is further suggested by normal values for lymphocyte ecto-adenosinetriphosphatase and ecto-nonspecific phosphatase. The data provide evidence for an enzyme deficiency in this X-linked, B lymphocyte deficiency syndrome."}
{"id": "PMID:27879", "title": "The abnormalities of beta-galactosidase in GM1-gangliosidoses.", "content": "The activity of GM1 beta-galactosidase in the brain and liver of patients with GM1-gangliosidosis was assayed using GM1-ganglioside tritiated in the terminal galactose. In the cases of GM1-gangliosidosis Types 1 and 2A the activity was less than 0.5% of the control. In the liver of GM1-gangliosidosis Type 2B the activity was observed to be much higher than that of Types 1 and 2A. On Sephadex G-150 gel filtration, three active fractions (I, II and III) for 4-methylumbelliferyl beta-galactopyranoside (4MU) and two active fractions (I and II) for GM1-ganglioside were obtained in the control liver. There was no active fraction for GM1-ganglioside in spite of the preserved fraction I for 4MU in the liver of GM1-gangliosidosis Type 1 or Type 2A. In any of the three cases fraction II for both 4MU and G71-ganglioside was not detected.", "contents": "The abnormalities of beta-galactosidase in GM1-gangliosidoses. The activity of GM1 beta-galactosidase in the brain and liver of patients with GM1-gangliosidosis was assayed using GM1-ganglioside tritiated in the terminal galactose. In the cases of GM1-gangliosidosis Types 1 and 2A the activity was less than 0.5% of the control. In the liver of GM1-gangliosidosis Type 2B the activity was observed to be much higher than that of Types 1 and 2A. On Sephadex G-150 gel filtration, three active fractions (I, II and III) for 4-methylumbelliferyl beta-galactopyranoside (4MU) and two active fractions (I and II) for GM1-ganglioside were obtained in the control liver. There was no active fraction for GM1-ganglioside in spite of the preserved fraction I for 4MU in the liver of GM1-gangliosidosis Type 1 or Type 2A. In any of the three cases fraction II for both 4MU and G71-ganglioside was not detected."}
{"id": "PMID:27884", "title": "Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia.", "content": "Changes in cerebral cortex concentrations of high-energy phosphates, glycolytic metabolites, citric acid cycle intermediates, associated amino acids, and ammonia, were studied after 5, 15 and 30 min of incomplete ischemia in rats anesthetized with 70% N2O or 150 mg.kg-1 of phenobartibal. Previous results have shown that with this type of ischemia (bilateral carotid artery occlusion combined with reduction in blood pressure to 50 mm Hg) cortical blood flow is reduced to below 10% of nitrous oxide values, whether animals are anesthetized with 70% N2O or 150 mg.kg-1 of phenobarbital. In animals under 70% N2O, changes in tissue concentrations of phosphocreatine, ATP, ADP and AMP were similar to those previously obtained in complete ischemia. However, some glucose remained in the tissue, and the lactate concentrations gradually rose to reach excessive values. Changes occuring in glycolytic and citric acid cycle intermediates were similar to those seen in complete ischemia but, after 30 min, there was some reduction in the pool size of amino acids. In those animals given phenobarbital and which lost all EEG activity during ischemia, changes in cerebral metabolites were virtually identical to those observed in nitrous oxide-anesthetized animals. However, some animals exposed to 5 or 15 min of ischemia had some remaining EEG activity. In these, cerebral energy state was significantly less deranged, and levels of glycogen, glucose and pyruvate were higher.", "contents": "Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. Changes in cerebral cortex concentrations of high-energy phosphates, glycolytic metabolites, citric acid cycle intermediates, associated amino acids, and ammonia, were studied after 5, 15 and 30 min of incomplete ischemia in rats anesthetized with 70% N2O or 150 mg.kg-1 of phenobartibal. Previous results have shown that with this type of ischemia (bilateral carotid artery occlusion combined with reduction in blood pressure to 50 mm Hg) cortical blood flow is reduced to below 10% of nitrous oxide values, whether animals are anesthetized with 70% N2O or 150 mg.kg-1 of phenobarbital. In animals under 70% N2O, changes in tissue concentrations of phosphocreatine, ATP, ADP and AMP were similar to those previously obtained in complete ischemia. However, some glucose remained in the tissue, and the lactate concentrations gradually rose to reach excessive values. Changes occuring in glycolytic and citric acid cycle intermediates were similar to those seen in complete ischemia but, after 30 min, there was some reduction in the pool size of amino acids. In those animals given phenobarbital and which lost all EEG activity during ischemia, changes in cerebral metabolites were virtually identical to those observed in nitrous oxide-anesthetized animals. However, some animals exposed to 5 or 15 min of ischemia had some remaining EEG activity. In these, cerebral energy state was significantly less deranged, and levels of glycogen, glucose and pyruvate were higher."}
{"id": "PMID:27891", "title": "Inhibition of 3'-methyl-4-dimethylaminoazobenezene-induced hepatocarcinogenesis by portacaval shunt.", "content": "Adult male Sprague Dalwey rats on which end-to-side portacaval shunt (PCS) operation was performed did not hyperplastic nodules and hepatoms when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controsl. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24-48 h, compared to the increase of 50-100% in non-operated rats. No clear tendency to a gradual increase in the activity of gamma-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5 1/2 months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibibiton of GT-ase increase induced by 3'Me-DAB in PCS-operated rats contrasted with an increase of GI-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'Me-DAB-induced hepatocarcinogenesis, manifested by lack preneoplastic morphologic changes and the absecnce of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen.", "contents": "Inhibition of 3'-methyl-4-dimethylaminoazobenezene-induced hepatocarcinogenesis by portacaval shunt. Adult male Sprague Dalwey rats on which end-to-side portacaval shunt (PCS) operation was performed did not hyperplastic nodules and hepatoms when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controsl. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24-48 h, compared to the increase of 50-100% in non-operated rats. No clear tendency to a gradual increase in the activity of gamma-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5 1/2 months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibibiton of GT-ase increase induced by 3'Me-DAB in PCS-operated rats contrasted with an increase of GI-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'Me-DAB-induced hepatocarcinogenesis, manifested by lack preneoplastic morphologic changes and the absecnce of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen."}
{"id": "PMID:27892", "title": "[Neurohumoral correlations and the effect of hydrocortisone on respiratory function in experimental pancreatitis].", "content": "From the observations on 18 patients and the experiments on 77 dogs with experimental pancreatitis neuro-humoral interrelations and hydrocortisone effect upon the respiratory function have been studied. Both in the clinic and in the experiment the authors have found the intermediate metabolism disturbed: adrenaline-like substances blood level rises, while the cholinergic complex blood level drops dramatically. The conclusion on a vital importance of a consecutive neuro-humoral correction with the use of cholinomimetics and corticosteroids in pancreatitis is drawn.", "contents": "[Neurohumoral correlations and the effect of hydrocortisone on respiratory function in experimental pancreatitis]. From the observations on 18 patients and the experiments on 77 dogs with experimental pancreatitis neuro-humoral interrelations and hydrocortisone effect upon the respiratory function have been studied. Both in the clinic and in the experiment the authors have found the intermediate metabolism disturbed: adrenaline-like substances blood level rises, while the cholinergic complex blood level drops dramatically. The conclusion on a vital importance of a consecutive neuro-humoral correction with the use of cholinomimetics and corticosteroids in pancreatitis is drawn."}
{"id": "PMID:27893", "title": "[Comparative assessment of the methods for surgical treatment of cryptorchism].", "content": "The experience with the surgical treatment of 305 cases of cryptorchism is presented. 108 Keetly and Torek's operations and 22 Mixter's operations have proved that in surgical technic the main emphasis should be transferred to the mobilization of the spermatic cord elements, but the orchoifixation should be simple and atraumatic. The Fowler's method of the descent of the testicles (107) in superficial inguinal ectopy and various modifications of the Petriwalsky's method of the descent of the testicles (43) in high inguinal retention and abdominal cryptorchism have made a favorable impression.", "contents": "[Comparative assessment of the methods for surgical treatment of cryptorchism]. The experience with the surgical treatment of 305 cases of cryptorchism is presented. 108 Keetly and Torek's operations and 22 Mixter's operations have proved that in surgical technic the main emphasis should be transferred to the mobilization of the spermatic cord elements, but the orchoifixation should be simple and atraumatic. The Fowler's method of the descent of the testicles (107) in superficial inguinal ectopy and various modifications of the Petriwalsky's method of the descent of the testicles (43) in high inguinal retention and abdominal cryptorchism have made a favorable impression."}
{"id": "PMID:27895", "title": "[The localisation of endocrine cells in the distal esophagus (author's transl)].", "content": "At the esophago-cardiac junction squamous epithelium is intermingled with gastric epithelium. Within the lamina propria of the distal 3 cm of the esophagus we found cardiac glands with many argyrophil cells in 60% of cases. Electron microscopy revealed seven well knonwn types and two further forms which we could not identify: EC, ECL, D, D1, AL, I eg. M, S. It is supposed that these cells are modified neurotransmitters with a local activity. Their function is local regulation of the lower esophageal sphincter (LES).", "contents": "[The localisation of endocrine cells in the distal esophagus (author's transl)]. At the esophago-cardiac junction squamous epithelium is intermingled with gastric epithelium. Within the lamina propria of the distal 3 cm of the esophagus we found cardiac glands with many argyrophil cells in 60% of cases. Electron microscopy revealed seven well knonwn types and two further forms which we could not identify: EC, ECL, D, D1, AL, I eg. M, S. It is supposed that these cells are modified neurotransmitters with a local activity. Their function is local regulation of the lower esophageal sphincter (LES)."}
{"id": "PMID:27901", "title": "Maintenance of 2,3-DPG and ATP levels in blood stored for 30 days at a constant pH obtained by variation of CO2.", "content": "A novel procedure for storing blood at a controlled pH consists in collecting blood in a pH 8.20, Tris-CPD solution and storing it in a special recipient including a gas permeable membrane under a CO2 atmosphere. The recipient is placed in an atmosphere of variable CO2 content, so that the initial alkalinity of the preservative is balanced by dissolved CO2, the proportion of which is diminished when lactate production increases with storage. 2,3-DPG and ATP were studied at three different pH levels of approximately 7.25, 7.45, and 7.65 at 4 degrees C. The best pH for the simultaneous maintenance of 2,3-DPG and ATP was 7.65. Under these conditions, 2,3-DPG is maintained at its initial level and ATP at 55% of its initial level at the 30th day. Lactate production is linear and hemolysis moderate.", "contents": "Maintenance of 2,3-DPG and ATP levels in blood stored for 30 days at a constant pH obtained by variation of CO2. A novel procedure for storing blood at a controlled pH consists in collecting blood in a pH 8.20, Tris-CPD solution and storing it in a special recipient including a gas permeable membrane under a CO2 atmosphere. The recipient is placed in an atmosphere of variable CO2 content, so that the initial alkalinity of the preservative is balanced by dissolved CO2, the proportion of which is diminished when lactate production increases with storage. 2,3-DPG and ATP were studied at three different pH levels of approximately 7.25, 7.45, and 7.65 at 4 degrees C. The best pH for the simultaneous maintenance of 2,3-DPG and ATP was 7.65. Under these conditions, 2,3-DPG is maintained at its initial level and ATP at 55% of its initial level at the 30th day. Lactate production is linear and hemolysis moderate."}
{"id": "PMID:27903", "title": "Production of valine by a Bacillus sp.", "content": "A bacterium isolated from Burdwan (India) soil was found to accumulate L-valine in the growth medium and identified to be a strain of Bacillus subtilis. The strain is able to grow and accumulate valine in a purely synthetic medium, but supplementation of the synthetic medium with either Casamino acids or yeast extract or with both, significantly improves the yield. The entire fermentation period can be divided into a growth phase and a production phase, which can be prolonged by adjustment of pH to the neutral range. Among the different carbon and nitrogen sources tested glucose at 8.5% and L-glutamic acid at 0.8%, respectively, were found most suitable. Cane sugar molasses tested as a substitute for glucose significantly stimulated growth but valine production was less. Different vitamins tested stimulated growth and valine yield and an inoculum level of 10% (v/v) of the medium was found to be optimal. The yield of valine under optimal conditions was found to be 4.53 g per litre of the medium. Valine has been isolated in crystalline form from the fermented broth by ion exchange resin chromatography and found to be a pure sample of the L-isomer.", "contents": "Production of valine by a Bacillus sp. A bacterium isolated from Burdwan (India) soil was found to accumulate L-valine in the growth medium and identified to be a strain of Bacillus subtilis. The strain is able to grow and accumulate valine in a purely synthetic medium, but supplementation of the synthetic medium with either Casamino acids or yeast extract or with both, significantly improves the yield. The entire fermentation period can be divided into a growth phase and a production phase, which can be prolonged by adjustment of pH to the neutral range. Among the different carbon and nitrogen sources tested glucose at 8.5% and L-glutamic acid at 0.8%, respectively, were found most suitable. Cane sugar molasses tested as a substitute for glucose significantly stimulated growth but valine production was less. Different vitamins tested stimulated growth and valine yield and an inoculum level of 10% (v/v) of the medium was found to be optimal. The yield of valine under optimal conditions was found to be 4.53 g per litre of the medium. Valine has been isolated in crystalline form from the fermented broth by ion exchange resin chromatography and found to be a pure sample of the L-isomer."}
{"id": "PMID:27909", "title": "[Circulating immune complexes in acute viral hepatitis, chronic active hepatitis, and periarteritis nodosa (author's transl)].", "content": "Circulating immune complexes were determined in patients with acute viral hepatitis, chronic active hepatitis and periarteriitis nodosa with the Raji cell technique. Circulating immune complexes were found in 11/18 HBsAg positive and HBsAg negative cases of acute viral hepatitis. In HBsAg positive chronic active hepatitis immune complexes were detectable in 42/43 cases but only in 1/27 HBsAg negative cases. Ten healthy HBsAg carriers demonstrated no detectable immune complexes. Using FITC conjugated antisera against HBs, HBc, and e antigen, immune complexes could not be found in any case of acute viral hepatitis or chronic active hepatitis. Elution of immune complexes from Raji demonstrated IgG, C'3 and a lack of HBsAg, HBc or e antigen. Immune complexes were present in 4/8 cases with periarteriitis nodosa. Viral components were detectable in one case.", "contents": "[Circulating immune complexes in acute viral hepatitis, chronic active hepatitis, and periarteritis nodosa (author's transl)]. Circulating immune complexes were determined in patients with acute viral hepatitis, chronic active hepatitis and periarteriitis nodosa with the Raji cell technique. Circulating immune complexes were found in 11/18 HBsAg positive and HBsAg negative cases of acute viral hepatitis. In HBsAg positive chronic active hepatitis immune complexes were detectable in 42/43 cases but only in 1/27 HBsAg negative cases. Ten healthy HBsAg carriers demonstrated no detectable immune complexes. Using FITC conjugated antisera against HBs, HBc, and e antigen, immune complexes could not be found in any case of acute viral hepatitis or chronic active hepatitis. Elution of immune complexes from Raji demonstrated IgG, C'3 and a lack of HBsAg, HBc or e antigen. Immune complexes were present in 4/8 cases with periarteriitis nodosa. Viral components were detectable in one case."}
{"id": "PMID:27927", "title": "[Psychophysiologic characteristics of the individual psychotropic activity of benzodiazepine derivatives under experimental conditions].", "content": "In 156 experiments performed on 41 cats with adequate experimental models of pseudoneurotic conditions, states of anxiety due to an electrostimulation of the hypothalamus through implanted electrodes and an emotional stress due to a conflict situation the authors compared the individual traits of the psychotropic activity of lorazepam, diazepam, chlordiazepoxide, oxazepam, nirazepam. These experiments permitted to display significant differences of psychophysiological structures in the tranquilizing effect of 5 benzodiazepine derivatives.", "contents": "[Psychophysiologic characteristics of the individual psychotropic activity of benzodiazepine derivatives under experimental conditions]. In 156 experiments performed on 41 cats with adequate experimental models of pseudoneurotic conditions, states of anxiety due to an electrostimulation of the hypothalamus through implanted electrodes and an emotional stress due to a conflict situation the authors compared the individual traits of the psychotropic activity of lorazepam, diazepam, chlordiazepoxide, oxazepam, nirazepam. These experiments permitted to display significant differences of psychophysiological structures in the tranquilizing effect of 5 benzodiazepine derivatives."}
{"id": "PMID:27929", "title": "A direct lead technique for histochemical demonstration of leucocyte alkaline phosphatase activity in blood smears.", "content": "A histochemical technique for demonstrating leucocyte alkaline phosphatase activity (LAP), based on direct precipitation of lead phosphate at pH 9.5, is described. The effect of fixative, temperature and stability of the medium on the activity of the enzyme and stability of the colour reaction was thoroughly studied. Peripheral blood smears obtained from both normal humans and pathological cases were studied and the results were compared with these obtained by the azo-dye method.", "contents": "A direct lead technique for histochemical demonstration of leucocyte alkaline phosphatase activity in blood smears. A histochemical technique for demonstrating leucocyte alkaline phosphatase activity (LAP), based on direct precipitation of lead phosphate at pH 9.5, is described. The effect of fixative, temperature and stability of the medium on the activity of the enzyme and stability of the colour reaction was thoroughly studied. Peripheral blood smears obtained from both normal humans and pathological cases were studied and the results were compared with these obtained by the azo-dye method."}
{"id": "PMID:27930", "title": "Effect of beta-sympatholytic agents on vascular responses to noradrenaline and potassium chloride.", "content": "Vasoconstrictory responses to noradrenaline (NA) or high potassium chloride (130 mM) usually show a biphasic behaviour: an initial peak is followed by a lower steady state level. The influence of three beta-sympatholytic agents (propranolol, pindolol, practolol) and a \"Ca-antagonist\" (verapamil) on this particular behaviour of KCl-induced vasoconstrictions was compared with responses to NA. Studies were performed on the intact vascular bed of an isolated intestinal preparation of the rat. 1. Increases in the concentration of propranolol and pindolol from 10(-10) to 10(-6) M attenuated the vascular responses to high KCl. Practolol, however, distinctly enhanced the KCl-responses. NA (1.3 microgram/ml)-elicited vasoconstriction was found to be influenced in a similar manner by the beta-receptor antagonists used, though lower concentrations of pindolol had an enhancing, higher concentrations a reducing effect on the constrictory responses to NA. 2. The extent to which the biphasic response adjusted to the steady state level was concentration-dependently increased KCl-responses and significantly decreased to a monophasic response to NA, in the presence of the beta-sympatholytic agents. 3. By using a quotient of deltaPs (steady-state phase) to deltaPi (initial vasoconstriction) and by comparing the effect of the three beta-sympatholytic agents with that of verapamil on this quotient showed a concentration-dependent decrease in presence of the beta-sympatholytic as well as of the Ca-antagonistic agents. These myotropic actions, i.e. negative influences on the mechanism of vascular smooth muscle activation ranged in the following sequence: Verapamil greater than propranolol greater than pindolol greater than practolol. 4. The mechanism underlying the biphasic responses to high potassium chloride are concluded to be basically different from the NA-responses because they are inversely affected by beta-sympatholytic agents. The steady-state response to KCl was found to be very sensitive to non-specific pharmacological actions of beta-sympatholytic substances. The myotropic action of the beta-receptor antagonists is compared with that of the Ca-antagonist verapamil and the role of calcium in the mechanism of activation of vascular smooth muscle is discussed.", "contents": "Effect of beta-sympatholytic agents on vascular responses to noradrenaline and potassium chloride. Vasoconstrictory responses to noradrenaline (NA) or high potassium chloride (130 mM) usually show a biphasic behaviour: an initial peak is followed by a lower steady state level. The influence of three beta-sympatholytic agents (propranolol, pindolol, practolol) and a \"Ca-antagonist\" (verapamil) on this particular behaviour of KCl-induced vasoconstrictions was compared with responses to NA. Studies were performed on the intact vascular bed of an isolated intestinal preparation of the rat. 1. Increases in the concentration of propranolol and pindolol from 10(-10) to 10(-6) M attenuated the vascular responses to high KCl. Practolol, however, distinctly enhanced the KCl-responses. NA (1.3 microgram/ml)-elicited vasoconstriction was found to be influenced in a similar manner by the beta-receptor antagonists used, though lower concentrations of pindolol had an enhancing, higher concentrations a reducing effect on the constrictory responses to NA. 2. The extent to which the biphasic response adjusted to the steady state level was concentration-dependently increased KCl-responses and significantly decreased to a monophasic response to NA, in the presence of the beta-sympatholytic agents. 3. By using a quotient of deltaPs (steady-state phase) to deltaPi (initial vasoconstriction) and by comparing the effect of the three beta-sympatholytic agents with that of verapamil on this quotient showed a concentration-dependent decrease in presence of the beta-sympatholytic as well as of the Ca-antagonistic agents. These myotropic actions, i.e. negative influences on the mechanism of vascular smooth muscle activation ranged in the following sequence: Verapamil greater than propranolol greater than pindolol greater than practolol. 4. The mechanism underlying the biphasic responses to high potassium chloride are concluded to be basically different from the NA-responses because they are inversely affected by beta-sympatholytic agents. The steady-state response to KCl was found to be very sensitive to non-specific pharmacological actions of beta-sympatholytic substances. The myotropic action of the beta-receptor antagonists is compared with that of the Ca-antagonist verapamil and the role of calcium in the mechanism of activation of vascular smooth muscle is discussed."}
{"id": "PMID:27932", "title": "Effects of alpha-adrenergic stimulation and blockade of plasma parathyroid hormone concentrations in cows.", "content": "Experiments were designed to investigate responses of immunoreactive parathyroid hormone (PTH) during alpha-adrenergic stimulation and blockade in cows. Alpha-adrenergic agonists (methoxamine, phenylephrine and noradrenaline, the beta-adrenergic action of which was blocked by propranolol) did not change PTH and free fatty acid levels, whereas they characteristically increased the blood pressure and decreased the heart rate. In contrast, alpha-adrenergic blockade by phentolamine progressively increased PTH levels. The elevated PTH concentrations, associated with increased plasma noradrenaline and free fatty acid levels, rising heart rate and decreasing blood pressure, indicated that all these changes can be related to a beta-adrenergic stimulatory mechanism. Beta-adrenergic stimulation was presumably responsible for the initial elevation of PTH concentrations, whereas, during the later phase of the phentolamine infusions, a concomitant hypocalcaemia probably also produced a stimulatory effect.", "contents": "Effects of alpha-adrenergic stimulation and blockade of plasma parathyroid hormone concentrations in cows. Experiments were designed to investigate responses of immunoreactive parathyroid hormone (PTH) during alpha-adrenergic stimulation and blockade in cows. Alpha-adrenergic agonists (methoxamine, phenylephrine and noradrenaline, the beta-adrenergic action of which was blocked by propranolol) did not change PTH and free fatty acid levels, whereas they characteristically increased the blood pressure and decreased the heart rate. In contrast, alpha-adrenergic blockade by phentolamine progressively increased PTH levels. The elevated PTH concentrations, associated with increased plasma noradrenaline and free fatty acid levels, rising heart rate and decreasing blood pressure, indicated that all these changes can be related to a beta-adrenergic stimulatory mechanism. Beta-adrenergic stimulation was presumably responsible for the initial elevation of PTH concentrations, whereas, during the later phase of the phentolamine infusions, a concomitant hypocalcaemia probably also produced a stimulatory effect."}
{"id": "PMID:27933", "title": "Testicular blood flow and testosterone concentrations in the spermatic venous blood in rats with experimental cryptorchidism.", "content": "Testicular blood flow and testosterone concentrations in the spermatic venous plasma were measured on unilaterally cryptorchid rats. Blood flow to the cryptorchid testis was 31.4 +/- 11.7 (SD) ml/100 g X min which was significantly higher thant that of the scrotal testis (17.7 +/- 4.4 ml/100 g X min). Stereological analysis showed a relative increase of blood vessel containing interstitial tissue in the cryptorchid testis, which was probably the main factor responsible for the relative increase of blood flow to the cryptorchid testis. The increase of interstitial tissue was greater than the increase of blood vessels and thus, the interstitium in the cryptorchid testis contained a number of vessels which was smaller than that of the interstitium in the scrotally located testis. The concentration of testosterone in the spermatic vein of the abdominal testis was 18.0 +/- 5.5 (SD) ng/ml and the corresponding value for the scrotal testis was 41.2 +/- 7.0 ng/ml. Calculations based on functional and morphological data indicate that the function of the Leydig cells in the abdominal testis was impaired. It was concluded that the outflow of testosterone from the cryptorchid testis was highly reduced.", "contents": "Testicular blood flow and testosterone concentrations in the spermatic venous blood in rats with experimental cryptorchidism. Testicular blood flow and testosterone concentrations in the spermatic venous plasma were measured on unilaterally cryptorchid rats. Blood flow to the cryptorchid testis was 31.4 +/- 11.7 (SD) ml/100 g X min which was significantly higher thant that of the scrotal testis (17.7 +/- 4.4 ml/100 g X min). Stereological analysis showed a relative increase of blood vessel containing interstitial tissue in the cryptorchid testis, which was probably the main factor responsible for the relative increase of blood flow to the cryptorchid testis. The increase of interstitial tissue was greater than the increase of blood vessels and thus, the interstitium in the cryptorchid testis contained a number of vessels which was smaller than that of the interstitium in the scrotally located testis. The concentration of testosterone in the spermatic vein of the abdominal testis was 18.0 +/- 5.5 (SD) ng/ml and the corresponding value for the scrotal testis was 41.2 +/- 7.0 ng/ml. Calculations based on functional and morphological data indicate that the function of the Leydig cells in the abdominal testis was impaired. It was concluded that the outflow of testosterone from the cryptorchid testis was highly reduced."}
{"id": "PMID:27934", "title": "Erythrocyte acetylcholinesterase activity changes in the early stages of anemic and hypobaric hypoxia or after CoCl2 treatment in rabbits.", "content": "The authors studied the changes of erythrocyte acetylcholinesterase (AChE) activity in rabbits respectively subjected to bleeding, hypobaric hypoxia and CoCl2 treatment; in such conditions a rise of the enzyme activity was observed. Similar increases take place also as a consequence of intravenous infusions carried out by using lactic or hydrochloric acid. The authors suggest that these increases in the erythrocyte AChE activity are connected with the decrease of the pCO2 that occurs in the various experimental conditions achieved.", "contents": "Erythrocyte acetylcholinesterase activity changes in the early stages of anemic and hypobaric hypoxia or after CoCl2 treatment in rabbits. The authors studied the changes of erythrocyte acetylcholinesterase (AChE) activity in rabbits respectively subjected to bleeding, hypobaric hypoxia and CoCl2 treatment; in such conditions a rise of the enzyme activity was observed. Similar increases take place also as a consequence of intravenous infusions carried out by using lactic or hydrochloric acid. The authors suggest that these increases in the erythrocyte AChE activity are connected with the decrease of the pCO2 that occurs in the various experimental conditions achieved."}
{"id": "PMID:27935", "title": "The adrenergic mechanism of the haemodynamic effects of massive doses of hydrocortisone in controlled haemorrhagic shock in the dog.", "content": "Haemorrhagic shock was induced in anaesthetized dogs by bleeding them into a blood reservoir system. By adjusting the blood level of the reservoir at a certain distance over the heart level the mean arterial blood pressure was kept at 6.7 kPa (50 mmHg). As has been found earlier, massive doses of hydrocortisone (80-560 mg.kg-1 body weight) caused a dose-dependent decrease in the total peripheral resistance. The degree of vasodilation distinctly increased during concomitant alpha-receptor blockade induced by phenoxybenzamine. The beta-receptor blocking drug propranolol efficiently inhibited the vasodilation caused by hydrocortisone and phenoxybenzamine. The findings fit with the hypothesis that massive doses of hydrocortisone induce an increased stimulation of the adrenergic beta2-receptors of the vascular smooth muscles.", "contents": "The adrenergic mechanism of the haemodynamic effects of massive doses of hydrocortisone in controlled haemorrhagic shock in the dog. Haemorrhagic shock was induced in anaesthetized dogs by bleeding them into a blood reservoir system. By adjusting the blood level of the reservoir at a certain distance over the heart level the mean arterial blood pressure was kept at 6.7 kPa (50 mmHg). As has been found earlier, massive doses of hydrocortisone (80-560 mg.kg-1 body weight) caused a dose-dependent decrease in the total peripheral resistance. The degree of vasodilation distinctly increased during concomitant alpha-receptor blockade induced by phenoxybenzamine. The beta-receptor blocking drug propranolol efficiently inhibited the vasodilation caused by hydrocortisone and phenoxybenzamine. The findings fit with the hypothesis that massive doses of hydrocortisone induce an increased stimulation of the adrenergic beta2-receptors of the vascular smooth muscles."}
{"id": "PMID:27936", "title": "Neuromuscular blockade of fazadinium bromide (AH 8165) in renal failure patients.", "content": "Fazadinium bromide (AH 8165) is a new non-depolarizing neuromuscular blocking agent with rapid onset of action and intermediate duration of effect. The characteristics of the neuromuscular blockade induced were compared in normal and renal failure patients by monitoring the mechanical responses of thumb adductor muscle to ulnar nerve stimulation. The data suggest that renal failure, even in anephric patients, does not influence the depth of neuromuscular relaxation when judged from the identical dose-effect curves in both groups of patients. Moreover, the duration of the neuromuscular block was not significantly increased in end-stage kidney failure patients, whether the initial or late phases of the spontaneous recovery of neuromuscular transmission were considered, and this occurred over the entire therapeutic range. However, additional incremental injections of fazadinium bromide should be used cautiously, as evidence appeared of prolonged duration of action. This agent, fazadinium bromide, may therefore present useful advantages to other non-depolarizing neuromuscular blocking agents as to clinical safety and effects in patients with renal insufficiency.", "contents": "Neuromuscular blockade of fazadinium bromide (AH 8165) in renal failure patients. Fazadinium bromide (AH 8165) is a new non-depolarizing neuromuscular blocking agent with rapid onset of action and intermediate duration of effect. The characteristics of the neuromuscular blockade induced were compared in normal and renal failure patients by monitoring the mechanical responses of thumb adductor muscle to ulnar nerve stimulation. The data suggest that renal failure, even in anephric patients, does not influence the depth of neuromuscular relaxation when judged from the identical dose-effect curves in both groups of patients. Moreover, the duration of the neuromuscular block was not significantly increased in end-stage kidney failure patients, whether the initial or late phases of the spontaneous recovery of neuromuscular transmission were considered, and this occurred over the entire therapeutic range. However, additional incremental injections of fazadinium bromide should be used cautiously, as evidence appeared of prolonged duration of action. This agent, fazadinium bromide, may therefore present useful advantages to other non-depolarizing neuromuscular blocking agents as to clinical safety and effects in patients with renal insufficiency."}
{"id": "PMID:27937", "title": "Cerebral metabolic rate of oxygen (CMRO2) in the acute phase of brain injury.", "content": "In 22 comatose patients with acute brain injury, the cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of the hemispheric cerebral blood flow (CBF) and the arteriovenous oxygen content difference. All patients were subjected to moderate sedation without barbiturates, normothermia and respiratory treatment. The CBF was calculated by the 133xenon washout method as the average of 16 regions. The results indicate high jugular venous oxygen tension and, in some studies, very low oxygen consumption. A critical, low CMRO2 was not found, and values of about 0.4 ml/100 g/min were compatible with restitution of intellectual function. The CMRO2 was unrelated to the clinical outcome and to the time after the trauma. In bilateral studies, the lowest values were measured in the most severely injured hemisphere.", "contents": "Cerebral metabolic rate of oxygen (CMRO2) in the acute phase of brain injury. In 22 comatose patients with acute brain injury, the cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of the hemispheric cerebral blood flow (CBF) and the arteriovenous oxygen content difference. All patients were subjected to moderate sedation without barbiturates, normothermia and respiratory treatment. The CBF was calculated by the 133xenon washout method as the average of 16 regions. The results indicate high jugular venous oxygen tension and, in some studies, very low oxygen consumption. A critical, low CMRO2 was not found, and values of about 0.4 ml/100 g/min were compatible with restitution of intellectual function. The CMRO2 was unrelated to the clinical outcome and to the time after the trauma. In bilateral studies, the lowest values were measured in the most severely injured hemisphere."}
{"id": "PMID:27938", "title": "Cerebral autoregulation in unconscious patients with brain injury.", "content": "In 18 unconscious patients with traumatic brain injury, the cerebral autoregulation was tested during the first 2-3 weeks after the acute trauma. Regional cerebral blood flow (rCBF) was measured by the intra-arterial 133xenon washout method before and after an increase of about 20% in the mean arterial blood pressure (MABP) by angiotensin. The difference between MABP and intraventricular pressure (IVP) was used as cerebral perfusion pressure (PP). Simultaneously, ventricular fluid pH, lactate and pyruvate were measured. Regional loss of autoregulation indicated by a 20% flow increase was observed in 29 out of 35 studies (83%), while hemispheric loss of autoregulation was observed in only one study. The results of the autoregulation tests were unrelated to the clinical outcome, the presence of brain-stem lesion, and the ventricular fluid pH, lactate and lactate/pyruvate ratio. In repeated studies, a gradual normalization of the autoregulation was observed about 5 days after the acute trauma.", "contents": "Cerebral autoregulation in unconscious patients with brain injury. In 18 unconscious patients with traumatic brain injury, the cerebral autoregulation was tested during the first 2-3 weeks after the acute trauma. Regional cerebral blood flow (rCBF) was measured by the intra-arterial 133xenon washout method before and after an increase of about 20% in the mean arterial blood pressure (MABP) by angiotensin. The difference between MABP and intraventricular pressure (IVP) was used as cerebral perfusion pressure (PP). Simultaneously, ventricular fluid pH, lactate and pyruvate were measured. Regional loss of autoregulation indicated by a 20% flow increase was observed in 29 out of 35 studies (83%), while hemispheric loss of autoregulation was observed in only one study. The results of the autoregulation tests were unrelated to the clinical outcome, the presence of brain-stem lesion, and the ventricular fluid pH, lactate and lactate/pyruvate ratio. In repeated studies, a gradual normalization of the autoregulation was observed about 5 days after the acute trauma."}
{"id": "PMID:27939", "title": "Haemodynamic effects of different corticosteroids in controlled haemorrhagic shock in the dog.", "content": "The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle.", "contents": "Haemodynamic effects of different corticosteroids in controlled haemorrhagic shock in the dog. The haemodynamic effects of massive doses of hydrocortisone (80-320 mg.kg-1), methylprednisolone (4-32 mg.kg-1), betamethasone (1.6-12.8 mg.kg-1) and aldosterone (0.1-0.8 mg.kg-1) and the interaction with phenoxybenzamine and propranolol have been studied during controlled haemorrhagic shock in the anaesthetized dog. Hydrocortisone was the only steroid which showed any significant vasodilating ability when given alone. The alpha-receptor blocking agent phenoxybenzamine distinctly decreased the total peripheral resistance. The effect of the phenoxybenzamine was increased in combination with hydrocortisone or methylprednisolone, especially if the steroid was given as the first drug. The vasodilation found was efficiently abolished by the beta-receptor blocking agent propranolol. The ability of hydrocortisone or methylprednisolone to potentiate phenoxybenzamine was not shared by betamethasone or aldosterone. Thus, the haemodynamic effect of the steroid does not seem to be correlated to either a glucocorticoid nor a mineralocorticoid effect. It is suggested that the steroid effect studied is related to the ability of hydrocortisone or methylprednisolone to block the extra neuronal amine uptake which decreases the rate of elimination of the sympathetic transmitter from the vicinity of the adrenergic receptor of the vascular smooth muscle."}
{"id": "PMID:27942", "title": "Effects of isoprenaline and dibutyryl-C-AMP on the electrical and mechanical activity of the rabbit myometrium.", "content": "Mechanical and electrical responses of spontaneously contracting muscle strips from oestrogen dominated rabbit uterus were investigated by the sucrose gap method. The effects of isoprenaline and dibutyryl-c-AMP in the presence and absence of propranolol were tested. It has been shown previously that the beta-adrenoceptor agonist isoprenaline inhibits the spontaneously contracting uterus even in the presence of the beta-blocker propranolol. The rise in c-amp which is caused by isoprenaline, is, however, blocked by propranolol. The aim of this investigation was to study further the role of c-AMP in the isoprenaline-induced relaxation of the uterus. Isoprenaline (10(-6) M) consistently abolished spikes and mechanical contractions, usually accompanied by hyperpolarization. Propranolol (3 X 10(-6) M) markedly reduced the incidence of hyperpolarization, but did not affect the other actions of isoprenaline. Hyperpolarization does not seem to be a prerequisite for inhibition of uterine contraction. Dibutyryl-c-AMP mimicked the actions of isoprenaline. No positive evidence to support a hypothesis of a c-AMP-independent mechanism was found. Therefore a possible explanation of the results could be that isoprenaline increases c-AMP in a small intracellular pool, mediating electrical and mechanical responses but not influenced by propranolol.", "contents": "Effects of isoprenaline and dibutyryl-C-AMP on the electrical and mechanical activity of the rabbit myometrium. Mechanical and electrical responses of spontaneously contracting muscle strips from oestrogen dominated rabbit uterus were investigated by the sucrose gap method. The effects of isoprenaline and dibutyryl-c-AMP in the presence and absence of propranolol were tested. It has been shown previously that the beta-adrenoceptor agonist isoprenaline inhibits the spontaneously contracting uterus even in the presence of the beta-blocker propranolol. The rise in c-amp which is caused by isoprenaline, is, however, blocked by propranolol. The aim of this investigation was to study further the role of c-AMP in the isoprenaline-induced relaxation of the uterus. Isoprenaline (10(-6) M) consistently abolished spikes and mechanical contractions, usually accompanied by hyperpolarization. Propranolol (3 X 10(-6) M) markedly reduced the incidence of hyperpolarization, but did not affect the other actions of isoprenaline. Hyperpolarization does not seem to be a prerequisite for inhibition of uterine contraction. Dibutyryl-c-AMP mimicked the actions of isoprenaline. No positive evidence to support a hypothesis of a c-AMP-independent mechanism was found. Therefore a possible explanation of the results could be that isoprenaline increases c-AMP in a small intracellular pool, mediating electrical and mechanical responses but not influenced by propranolol."}
{"id": "PMID:27945", "title": "The release of serotonin from rat duodenal enterochromaffin cells by adrenoceptor agonists studied in vitro.", "content": "The serotonin (5-HT) content of enterochromaffin cells (EC) was studied by a cytofluorimetric method in biopsies from rat duodenal mucosa after in vitro incubation with different adrenoceptor agonists and antagonists and acetylcholine (ACh). Noradrenaline (NA), Adrenaline (A) and Isoprenaline (IP) caused a decrease of 5-HT in EC down to 40--60% and for NA and A this effect was concentration-dependent. The effect was antagonized by d,1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine indicating that the 5-HT release from EC is probably mediated via a true beta-adrenoceptor mechanism possibly of the beta2 type. ACh also decreased the 5-HT content of EC but was much less potent than the adrenergic substances. Dopamine (DA) had no effect.", "contents": "The release of serotonin from rat duodenal enterochromaffin cells by adrenoceptor agonists studied in vitro. The serotonin (5-HT) content of enterochromaffin cells (EC) was studied by a cytofluorimetric method in biopsies from rat duodenal mucosa after in vitro incubation with different adrenoceptor agonists and antagonists and acetylcholine (ACh). Noradrenaline (NA), Adrenaline (A) and Isoprenaline (IP) caused a decrease of 5-HT in EC down to 40--60% and for NA and A this effect was concentration-dependent. The effect was antagonized by d,1-propranolol but not by d-propranolol, metoprolol, phentolamine or phenoxybenzamine indicating that the 5-HT release from EC is probably mediated via a true beta-adrenoceptor mechanism possibly of the beta2 type. ACh also decreased the 5-HT content of EC but was much less potent than the adrenergic substances. Dopamine (DA) had no effect."}
{"id": "PMID:27948", "title": "Comparative evaluation of hypnotic efficacy of flunitrazepam in psychiatric in-patients.", "content": "Flunitrazepam in 2-mg and 4-mg doses was compared with flurazepam 30 mg and nitrazepam 10 mg for hypnotic efficacy in a double-blind, multiple cross-over trial involving 41 psychiatric in-patients. In the vast majority of comparisons involving a number of sleep parameters differences did not reach significance level. Flunitrazepam 4 mg tended to produce the shortest latency time and the longest duration of sleep but also the most side-effects. Nitrazepam 10 mg appeared to have a slight advantage over the other drugs in terms of patient preference. For severe sleep disturbance flunitrazepam 2 mg tended to be the most satisfactory drug in terms of efficacy and paucity of side-effects.", "contents": "Comparative evaluation of hypnotic efficacy of flunitrazepam in psychiatric in-patients. Flunitrazepam in 2-mg and 4-mg doses was compared with flurazepam 30 mg and nitrazepam 10 mg for hypnotic efficacy in a double-blind, multiple cross-over trial involving 41 psychiatric in-patients. In the vast majority of comparisons involving a number of sleep parameters differences did not reach significance level. Flunitrazepam 4 mg tended to produce the shortest latency time and the longest duration of sleep but also the most side-effects. Nitrazepam 10 mg appeared to have a slight advantage over the other drugs in terms of patient preference. For severe sleep disturbance flunitrazepam 2 mg tended to be the most satisfactory drug in terms of efficacy and paucity of side-effects."}
{"id": "PMID:27949", "title": "Neuroendocrine disorders in depressions and their significance for the monoamine hypothesis of depression.", "content": "This article discusses the results of recent neuroendocrinological research in depressions. The abnormalities found in a given category of vital depressive patients--cortisol hypersecretion, decreased growth hormone response to insulin hypoglycaemia and decreased luteinizing hormone secretion in menopause--are believed to be due to deficient noradrenalin-(NA)-ergic activity in the hypothalmus. Thus explained, they support the so-called MA (monoamine) hypothesis, which postulates that a functional NA deficiency in the brain plays a role in the pathogenesis of certain types of vital depression. Disorders in certain central MA-ergic systems are predictive of disorders in the hormone secretion of the anterior pituitary. Inversely, disorders in the hormone secretion of the anterior pituitary can be indicative of disorders in the MA-ergic transmission in the hypothalamus. Consequently we can expect a convergence of transmitter research and neuroendocrinological research--two lines of research which have so far been largely separated in studies of human individuals.", "contents": "Neuroendocrine disorders in depressions and their significance for the monoamine hypothesis of depression. This article discusses the results of recent neuroendocrinological research in depressions. The abnormalities found in a given category of vital depressive patients--cortisol hypersecretion, decreased growth hormone response to insulin hypoglycaemia and decreased luteinizing hormone secretion in menopause--are believed to be due to deficient noradrenalin-(NA)-ergic activity in the hypothalmus. Thus explained, they support the so-called MA (monoamine) hypothesis, which postulates that a functional NA deficiency in the brain plays a role in the pathogenesis of certain types of vital depression. Disorders in certain central MA-ergic systems are predictive of disorders in the hormone secretion of the anterior pituitary. Inversely, disorders in the hormone secretion of the anterior pituitary can be indicative of disorders in the MA-ergic transmission in the hypothalamus. Consequently we can expect a convergence of transmitter research and neuroendocrinological research--two lines of research which have so far been largely separated in studies of human individuals."}
{"id": "PMID:27950", "title": "Primary culture of adult rat liver cells. III. Hormonal effects on cytological and biochemical properties of primary cultured cells.", "content": "The effect of various hormones on cytological and biochemical properties of cultured hepatic cells were investigated in order to obtain long-term survival of the hepatocytes with adult liver functions in primary culture. Insulin supplementation of the culture medium enhanced the attachemnt efficiency of cells in primary culture without affecting either maintenance of morphological characters of epithelial cells or retention of liver-specific functions in cultured cells. A combination of dexamethasone and insulin was apparently effective in stimulating the formation of a monolayer of polygonal cells with granular cytoplasm and in maintenance of liver-specific functions for relatively longer periods. Supplementation with either dexamethasone or hydrocortisone alone enhanced tyrosine aminotransferase activities in cultured cells for at least 4 days postinoculation. These steroid hormones also allowed growth of small epithelial cells with clear cytoplasm and maintenance of increased albumin production for 8 days after inoculation. The roles of these hormones in the primary culture of isolated hepatic cells are discussed in the present paper.", "contents": "Primary culture of adult rat liver cells. III. Hormonal effects on cytological and biochemical properties of primary cultured cells. The effect of various hormones on cytological and biochemical properties of cultured hepatic cells were investigated in order to obtain long-term survival of the hepatocytes with adult liver functions in primary culture. Insulin supplementation of the culture medium enhanced the attachemnt efficiency of cells in primary culture without affecting either maintenance of morphological characters of epithelial cells or retention of liver-specific functions in cultured cells. A combination of dexamethasone and insulin was apparently effective in stimulating the formation of a monolayer of polygonal cells with granular cytoplasm and in maintenance of liver-specific functions for relatively longer periods. Supplementation with either dexamethasone or hydrocortisone alone enhanced tyrosine aminotransferase activities in cultured cells for at least 4 days postinoculation. These steroid hormones also allowed growth of small epithelial cells with clear cytoplasm and maintenance of increased albumin production for 8 days after inoculation. The roles of these hormones in the primary culture of isolated hepatic cells are discussed in the present paper."}
{"id": "PMID:27946", "title": "[Actual knowledge on beta blocking agents in psychiatry (author's transl)].", "content": "A new group of substances blocking central beta receptors, ie beta blocking agents among which oxprenol and pindolol, have been used in psychiatry, mainly in anxious or depressive-anxious patients. The anxiolytic effect, particularly on somatic anxiety, is interesting, and is present in double blind studies with benzodiazepines, where it is superior to these classical agents. The author has observed this therapeutic activity in series of one hundred patients and also a dynamising effect in some of these patients. Without having observed by himself and possibly because of the low doses experimented, the author states that these drugs have an antipsychotic activity.", "contents": "[Actual knowledge on beta blocking agents in psychiatry (author's transl)]. A new group of substances blocking central beta receptors, ie beta blocking agents among which oxprenol and pindolol, have been used in psychiatry, mainly in anxious or depressive-anxious patients. The anxiolytic effect, particularly on somatic anxiety, is interesting, and is present in double blind studies with benzodiazepines, where it is superior to these classical agents. The author has observed this therapeutic activity in series of one hundred patients and also a dynamising effect in some of these patients. Without having observed by himself and possibly because of the low doses experimented, the author states that these drugs have an antipsychotic activity."}
{"id": "PMID:27953", "title": "Resonance Raman studies on the ligand-iron interactions in hemoproteins and metallo-porphyrins.", "content": "The resonance Raman spectra (RRS) were measured for various hemoproteins, as well as for free hemes, and analysed in terms of the interactions between the porphyrin ring and the heme iron and between the axial ligand and the heme iron. To establish vibrational assignments, the RRS of metallo-octae-thylporphyrin (M(OEP)), its 15N substituted and meso-deuterated derivatives were measured. It was found that the Raman line corresponding to the oxidation state marker of hemoproteins involves appreciable displacement of the pyrrolic nitrogen atoms toward metal ion but not that of methine bridges and that the frequencies of methine-bridge CC stretching vibrations are altered by the conjugation interaction between the porphyrin ring and the metal ion present. The prominent Raman lines of Ni(OEP) were assigned on the basis of the normal coordinate analysis. The Raman spectra of heme a bis-imidazole complex (Fe(A)(Im)2) in the presence of cyanide changed when pH was reduced to neutral. It implied formation of cyanhydrin at the peripheral formyl group of heme a. The Fe(A)(Im)2 formed an addition compound with NaHSO3 in a neutral solution but the added NaHSO3 was eliminated when the heme iron was reduced. The Raman spectra of hemoproteins were classified into four groups on the basis of the relative intensities and frequencies of the four key bands. It demonstrated the existence of two kinds of ferrous low-spin states. The difference between the two species was attributed to the difference in the nature of chemical bond between the heme iron and its sixth ligand (L). The Fe-L bonds of ferrous low-spin molecules in Groups A and C are mainly associated with the dz2(Fe)-lone pair and dz(Fe)-II(L) interactions, respectively. This interpretation of the Raman spectra appears consistent with the experimental facts that the ferrous low-spin molecules in Group C photodissociate upon illumination of light at the Soret band and also that the internal stretching frequencies of the sixth ligand are shifted to lower frequency upon coordination to the heme iron. The frequency of the oxidation state marker of reduced cytochrome P-450 (P-450cam) was unusually low in comparison with those of other hemoproteins. It was ascribed to delocalization of electrons from the thiolate anion to the porphyrin II*(ring) orbital through the pi-type molecular orbital (Eq.3). The RRS of reduced P-450cam.metyrapone adduct was quite close to that of reduced cytochrome b5. In conclusion, the Raman frequencies of hemoproteins may depend primarily upon the amount of electrons delocalized to the II* orbital of the porphyrin ring. The coordination of lone-pair electrons of the axial ligand to the iron dz2 orbital yields bond energy but scarcely affects the Raman frequencies. If the pi orbital of the axial ligand interacts with the iron dpi orbital, it perturbs the delocalization of the dpi(Fe) electrons to the II*(ring) orbital of porphyrin ring and thus affects the Raman frequencies.", "contents": "Resonance Raman studies on the ligand-iron interactions in hemoproteins and metallo-porphyrins. The resonance Raman spectra (RRS) were measured for various hemoproteins, as well as for free hemes, and analysed in terms of the interactions between the porphyrin ring and the heme iron and between the axial ligand and the heme iron. To establish vibrational assignments, the RRS of metallo-octae-thylporphyrin (M(OEP)), its 15N substituted and meso-deuterated derivatives were measured. It was found that the Raman line corresponding to the oxidation state marker of hemoproteins involves appreciable displacement of the pyrrolic nitrogen atoms toward metal ion but not that of methine bridges and that the frequencies of methine-bridge CC stretching vibrations are altered by the conjugation interaction between the porphyrin ring and the metal ion present. The prominent Raman lines of Ni(OEP) were assigned on the basis of the normal coordinate analysis. The Raman spectra of heme a bis-imidazole complex (Fe(A)(Im)2) in the presence of cyanide changed when pH was reduced to neutral. It implied formation of cyanhydrin at the peripheral formyl group of heme a. The Fe(A)(Im)2 formed an addition compound with NaHSO3 in a neutral solution but the added NaHSO3 was eliminated when the heme iron was reduced. The Raman spectra of hemoproteins were classified into four groups on the basis of the relative intensities and frequencies of the four key bands. It demonstrated the existence of two kinds of ferrous low-spin states. The difference between the two species was attributed to the difference in the nature of chemical bond between the heme iron and its sixth ligand (L). The Fe-L bonds of ferrous low-spin molecules in Groups A and C are mainly associated with the dz2(Fe)-lone pair and dz(Fe)-II(L) interactions, respectively. This interpretation of the Raman spectra appears consistent with the experimental facts that the ferrous low-spin molecules in Group C photodissociate upon illumination of light at the Soret band and also that the internal stretching frequencies of the sixth ligand are shifted to lower frequency upon coordination to the heme iron. The frequency of the oxidation state marker of reduced cytochrome P-450 (P-450cam) was unusually low in comparison with those of other hemoproteins. It was ascribed to delocalization of electrons from the thiolate anion to the porphyrin II*(ring) orbital through the pi-type molecular orbital (Eq.3). The RRS of reduced P-450cam.metyrapone adduct was quite close to that of reduced cytochrome b5. In conclusion, the Raman frequencies of hemoproteins may depend primarily upon the amount of electrons delocalized to the II* orbital of the porphyrin ring. The coordination of lone-pair electrons of the axial ligand to the iron dz2 orbital yields bond energy but scarcely affects the Raman frequencies. If the pi orbital of the axial ligand interacts with the iron dpi orbital, it perturbs the delocalization of the dpi(Fe) electrons to the II*(ring) orbital of porphyrin ring and thus affects the Raman frequencies."}
{"id": "PMID:27947", "title": "[Flunitrazepam and memory (author's transl)].", "content": "This work is based on the observation of memory troubles before sleep in patients with sleep problems treated with flunitrazepam. Eight subjects are tested in two sessions, flunitrazepam and placebo, in double blind, with memory tests given the evening after medication and controlled the next morning. One additional test is controlling vigilance. The results show that memory is significantly disturbed by flunitrazepam, both for direct and delayed memory, the next day. On the contrary, recognition is not altered, neither vigilance.", "contents": "[Flunitrazepam and memory (author's transl)]. This work is based on the observation of memory troubles before sleep in patients with sleep problems treated with flunitrazepam. Eight subjects are tested in two sessions, flunitrazepam and placebo, in double blind, with memory tests given the evening after medication and controlled the next morning. One additional test is controlling vigilance. The results show that memory is significantly disturbed by flunitrazepam, both for direct and delayed memory, the next day. On the contrary, recognition is not altered, neither vigilance."}
{"id": "PMID:27954", "title": "Nuclear magnetic resonance studies of high-spin ferric hemoproteins.", "content": "220 MHz proton Fourier transform (FT) NMR with quadrature phase detection (QPD) technique is applied to observe largely hyperfine-shifted signals of various hemoproteins and hemoenzymes in ferric high-spin state. The binding of F-, OCN-, SCN-, and CH3OH to the ferric heme iron in high-spin state in various hemoproteins has been studied by the use of FT/QPD technique at 220 MHz. The binding of formate ion to metmyoglobin (metMb) has also been studied. The spectrum of the formate complex was compared with that of hemoglobin M Milwaukee where carboxylate groups are bound to the hemes of the beta subunits. The acid-base transition of ferric myoglobin (Mb) was confirmed by monitoring the pH-dependent shift of the heme side methyl signals with the reflection point at pH 9.1. This finding is analyzed on the basis of rapid exchange between alkaline (low spin) and acidic (high spin) forms accompanied by the dissociation and association of one proton in the ferric Mb. The structure of the heme environment of ferric horseradish peroxidase (HRP) was studied. The pH-dependent features of NMR spectra of the ferric enzyme and its complexes with cyanide and azide were discussed in terms of heme environmental structures, comparing with the case of metMb. The results were interpreted as follows: There exists an ionizable amino group near the heme responsible for the ligand binding reactions of the enzyme, which modulates the entry of external azide to the heme iron through protolytic equilibrium of this group. The pK value of this group was determined to be 5.9 by monitoring the pH-dependent shift of the heme peripheral methyl signals of the native enzyme, indicating that the group is probably a histidyl residue. Acid-alkaline transition of metMb was confirmed to associate with the proton dissociation of an iron-bound water molecule, whereas in HRP, pH-dependent spin state change characterized by pK 11 is attributed not to the simple protolytic reaction of the iron-bound water but to the direct coordination of an amino acid residue of the polypeptide chain to the ferric heme iron. Histidyl imidazole is a possible candidate for the new sixth iron ligand in alkaline peroxidase above pH 11. Interaction of HRP with electron donor(indolepropionic acid, IPA) was also studied. The hyperfine-shifted proton signals of the heme peripheral groups of the enzyme showed a small but significant shift with stepwise additions of IPA, indicating that the donor binds at a specific site of HRP. There results are interpreted in terms of the interaction between the enzyme and the donor at the heme edge site.", "contents": "Nuclear magnetic resonance studies of high-spin ferric hemoproteins. 220 MHz proton Fourier transform (FT) NMR with quadrature phase detection (QPD) technique is applied to observe largely hyperfine-shifted signals of various hemoproteins and hemoenzymes in ferric high-spin state. The binding of F-, OCN-, SCN-, and CH3OH to the ferric heme iron in high-spin state in various hemoproteins has been studied by the use of FT/QPD technique at 220 MHz. The binding of formate ion to metmyoglobin (metMb) has also been studied. The spectrum of the formate complex was compared with that of hemoglobin M Milwaukee where carboxylate groups are bound to the hemes of the beta subunits. The acid-base transition of ferric myoglobin (Mb) was confirmed by monitoring the pH-dependent shift of the heme side methyl signals with the reflection point at pH 9.1. This finding is analyzed on the basis of rapid exchange between alkaline (low spin) and acidic (high spin) forms accompanied by the dissociation and association of one proton in the ferric Mb. The structure of the heme environment of ferric horseradish peroxidase (HRP) was studied. The pH-dependent features of NMR spectra of the ferric enzyme and its complexes with cyanide and azide were discussed in terms of heme environmental structures, comparing with the case of metMb. The results were interpreted as follows: There exists an ionizable amino group near the heme responsible for the ligand binding reactions of the enzyme, which modulates the entry of external azide to the heme iron through protolytic equilibrium of this group. The pK value of this group was determined to be 5.9 by monitoring the pH-dependent shift of the heme peripheral methyl signals of the native enzyme, indicating that the group is probably a histidyl residue. Acid-alkaline transition of metMb was confirmed to associate with the proton dissociation of an iron-bound water molecule, whereas in HRP, pH-dependent spin state change characterized by pK 11 is attributed not to the simple protolytic reaction of the iron-bound water but to the direct coordination of an amino acid residue of the polypeptide chain to the ferric heme iron. Histidyl imidazole is a possible candidate for the new sixth iron ligand in alkaline peroxidase above pH 11. Interaction of HRP with electron donor(indolepropionic acid, IPA) was also studied. The hyperfine-shifted proton signals of the heme peripheral groups of the enzyme showed a small but significant shift with stepwise additions of IPA, indicating that the donor binds at a specific site of HRP. There results are interpreted in terms of the interaction between the enzyme and the donor at the heme edge site."}
{"id": "PMID:27955", "title": "Analysis of acid-base properties of peroxidase and myoglobin.", "content": "Two heme-linked groups of horseradish peroxidases, characterized by pKa = 5.8 (isoenzyme A) and 7.3 (isoenzyme C), are believed to be distal amino acid residues and, judging by their acid-base properties in various derivatives, influence the functions of these isoenzymes. In contrast, in myoglobin ionization of the distal histidine does not influence its reactivity. Accordingly, we conclude that the interaction of the distal base with a 6th ligand is weak in myoglobin but very strong in peroxidases.", "contents": "Analysis of acid-base properties of peroxidase and myoglobin. Two heme-linked groups of horseradish peroxidases, characterized by pKa = 5.8 (isoenzyme A) and 7.3 (isoenzyme C), are believed to be distal amino acid residues and, judging by their acid-base properties in various derivatives, influence the functions of these isoenzymes. In contrast, in myoglobin ionization of the distal histidine does not influence its reactivity. Accordingly, we conclude that the interaction of the distal base with a 6th ligand is weak in myoglobin but very strong in peroxidases."}
{"id": "PMID:27956", "title": "Conformational change and cooperative ligand binding in hemoglobin.", "content": "Although many studies have been carried out on the cooperativityly of ligand binding to hemoglobin, its molecular mechanism is not yet completely confirmed. Various models have been proposed on one hand, but on the other hand the direct judgement of the validity of each model is confronted with experimental difficulties. With this situation in mind, we re-examine carefully various kinds of experimental data, with the intention of finding any hints for future studies on the molecular mechanism of the cooperativity of ligand binding not only to hemoglobin but also to other allosteric proteins composed of subunits. As a result of these re-examinations most of the experimental data can be consistently explained from the viewpoint that the strain due to ligation is transmitted to the interfaces of the subunits and the degree of the strain stored in the interfaces between the subunits controls the cooperativity of of ligand binding. The subjects selected to the present study are molecular structural differences between the deoxy- and oxy-hemoglobin, temperature dependence of oxygen equilibrium constants, and recombination curves of carbon monoxide in flash photolysis experiments. In the first section, the difference of the interfaces of the subunits between deoxy- and oxy-hemoglobin is investigated on the basis of the atomic coordinates determined by Perutz et al. and we examine energetically which of the segment's pairs contributes mainly to the difference in the molecular structure between the two forms. On the basis of this investigation, it is shown in the next section that the oxygen equilibrium constants of human adult hemoglobin under normal physiological conditions are well explained by the following sequence of the conformational changes. The local changes in the interfaces of the subunits are reflected directly on the small differences among the first three Adair constants and the succeeding rearrangement to the four subunits causes the outstandingly larger value of the fourth Adair constant. In more alkaline pH, this rearrangement begins to occur at the earlier stages of ligation. In the succeeding section, it is pointed out that the property of this rearrangement can be studied in more detail through the recombination curves followed by flash photolysis under special conditions.", "contents": "Conformational change and cooperative ligand binding in hemoglobin. Although many studies have been carried out on the cooperativityly of ligand binding to hemoglobin, its molecular mechanism is not yet completely confirmed. Various models have been proposed on one hand, but on the other hand the direct judgement of the validity of each model is confronted with experimental difficulties. With this situation in mind, we re-examine carefully various kinds of experimental data, with the intention of finding any hints for future studies on the molecular mechanism of the cooperativity of ligand binding not only to hemoglobin but also to other allosteric proteins composed of subunits. As a result of these re-examinations most of the experimental data can be consistently explained from the viewpoint that the strain due to ligation is transmitted to the interfaces of the subunits and the degree of the strain stored in the interfaces between the subunits controls the cooperativity of of ligand binding. The subjects selected to the present study are molecular structural differences between the deoxy- and oxy-hemoglobin, temperature dependence of oxygen equilibrium constants, and recombination curves of carbon monoxide in flash photolysis experiments. In the first section, the difference of the interfaces of the subunits between deoxy- and oxy-hemoglobin is investigated on the basis of the atomic coordinates determined by Perutz et al. and we examine energetically which of the segment's pairs contributes mainly to the difference in the molecular structure between the two forms. On the basis of this investigation, it is shown in the next section that the oxygen equilibrium constants of human adult hemoglobin under normal physiological conditions are well explained by the following sequence of the conformational changes. The local changes in the interfaces of the subunits are reflected directly on the small differences among the first three Adair constants and the succeeding rearrangement to the four subunits causes the outstandingly larger value of the fourth Adair constant. In more alkaline pH, this rearrangement begins to occur at the earlier stages of ligation. In the succeeding section, it is pointed out that the property of this rearrangement can be studied in more detail through the recombination curves followed by flash photolysis under special conditions."}
{"id": "PMID:27964", "title": "The effect of inhibitors of cellular RNA synthesis on stimulation of mouse encephalomyocarditis virus reproduction by poliovirus in HeLa and MIO cells.", "content": "Inoculation of HeLa and MIO cells with a guanidine-dependent mutant of poliovirus (gd-polio) in the absence of guanidine resulted in stimulation of mouse encephalomyocarditis (EMC) virus reproduction. No stimulation was found to occur in the presence of actinomycin D, on pre-treatment of the cells with cordycepin, or on their UV irradiation or enucleation. In contrast to HeLa cells, the enhancement of EMC virus reproduction by gd-polio in MIO cells required no current synthesis of cellular RNAs: it occurred in the presence of actinomycin D, upon UV irradiation of the cells or their enucleation. The possible mechanisms of the stimulating effect of poliovirus in HeLa and MIO cells are discussed.", "contents": "The effect of inhibitors of cellular RNA synthesis on stimulation of mouse encephalomyocarditis virus reproduction by poliovirus in HeLa and MIO cells. Inoculation of HeLa and MIO cells with a guanidine-dependent mutant of poliovirus (gd-polio) in the absence of guanidine resulted in stimulation of mouse encephalomyocarditis (EMC) virus reproduction. No stimulation was found to occur in the presence of actinomycin D, on pre-treatment of the cells with cordycepin, or on their UV irradiation or enucleation. In contrast to HeLa cells, the enhancement of EMC virus reproduction by gd-polio in MIO cells required no current synthesis of cellular RNAs: it occurred in the presence of actinomycin D, upon UV irradiation of the cells or their enucleation. The possible mechanisms of the stimulating effect of poliovirus in HeLa and MIO cells are discussed."}
{"id": "PMID:27965", "title": "Marked difference in electrophoretic migration rates between two influenza A viruses.", "content": "Comparative moving boundary electrophoresis revealed that influenza virus A/PR/8/34 (H0N1) has a 2.5 times higher electrophoretic migration rate at pH 7 than influenza virus A/Singpore/1/57 (H2N2). This difference was the same whether the compared viruses were purified first by either ammonium sulphate precipitation or adsorption onto and elution from red blood cells and then by density gradient centrifugation. The same electrophoretic methods was used for testing the homogeneity of influenza virus preparations purified by either method.", "contents": "Marked difference in electrophoretic migration rates between two influenza A viruses. Comparative moving boundary electrophoresis revealed that influenza virus A/PR/8/34 (H0N1) has a 2.5 times higher electrophoretic migration rate at pH 7 than influenza virus A/Singpore/1/57 (H2N2). This difference was the same whether the compared viruses were purified first by either ammonium sulphate precipitation or adsorption onto and elution from red blood cells and then by density gradient centrifugation. The same electrophoretic methods was used for testing the homogeneity of influenza virus preparations purified by either method."}
{"id": "PMID:27966", "title": "Multiplication of herpes simplex virus types 1 and 2 in macrophages of NMRI and C57/BL mice.", "content": "The multiplication of 8 strains of herpes simplex virus of type 1 and 2 in normal and stimulated macrophages of NMRI and C57/bl mice was tested. Only 3 strains multiplied in normal NMRI macrophages, whereas all strains multiplied in stimulated cells. No multiplication except of one strain was observed in C57/bl macrophages. The multiplication rates of the virus strains correlated well with the determination of the acid-soluble and acid-insoluble thymidine (dTR) radioactivity and autoradiographic studies of infected (normal and stimulated) NMRI and C57/bl macrophages. The influence of the age of mice used for obtaining the macrophages was also studied. In stimulated macrophages more viral DNA was synthesised than in non-stimulated cells.", "contents": "Multiplication of herpes simplex virus types 1 and 2 in macrophages of NMRI and C57/BL mice. The multiplication of 8 strains of herpes simplex virus of type 1 and 2 in normal and stimulated macrophages of NMRI and C57/bl mice was tested. Only 3 strains multiplied in normal NMRI macrophages, whereas all strains multiplied in stimulated cells. No multiplication except of one strain was observed in C57/bl macrophages. The multiplication rates of the virus strains correlated well with the determination of the acid-soluble and acid-insoluble thymidine (dTR) radioactivity and autoradiographic studies of infected (normal and stimulated) NMRI and C57/bl macrophages. The influence of the age of mice used for obtaining the macrophages was also studied. In stimulated macrophages more viral DNA was synthesised than in non-stimulated cells."}
{"id": "PMID:27967", "title": "Haemagglutination inhibition antibodies in nasal secretions of persons after natural parainfluenza virus infection.", "content": "In 7 adults and 7 children with upper respiratory illness of parainfluenza aetiology, the virus was isolated in the acute phase from nasal washings or nasal smears in spite of high titres of haemagglutination inhibition (HI) antibodies in serum. By contrast, secretory HI antibodies were not demonstrated at the onset of illness in any of the patients, but their formation started early and the antibodies reached maximal levels about 10 days after onset of illness. The individual patients showed considerable differences in the dynamics of secretory antibody formation and especially in their persistence. In some of the patients, secretory antibodies were demonstrated as late as 12 months after the illness.", "contents": "Haemagglutination inhibition antibodies in nasal secretions of persons after natural parainfluenza virus infection. In 7 adults and 7 children with upper respiratory illness of parainfluenza aetiology, the virus was isolated in the acute phase from nasal washings or nasal smears in spite of high titres of haemagglutination inhibition (HI) antibodies in serum. By contrast, secretory HI antibodies were not demonstrated at the onset of illness in any of the patients, but their formation started early and the antibodies reached maximal levels about 10 days after onset of illness. The individual patients showed considerable differences in the dynamics of secretory antibody formation and especially in their persistence. In some of the patients, secretory antibodies were demonstrated as late as 12 months after the illness."}
{"id": "PMID:27968", "title": "Cell- and antibody-mediated responses to measles and mumps viruses in experimental animals.", "content": "Monkeys and guinea pigs were immunized with various doses of measles and mumps viruses. A cell-mediated response measured by leukocyte migration inhibition occured during the first two weeks after immunization. In case of measles virus, marked migration inhibition occurred already on the 7th day in monkeys and guinea pigs immunized with high virus doses. The response declined as early as 14 days after immunization in contrast to the group of guinea pigs inoculated with a lower virus dose. In these animals the response sustained for up to 50 days. Immunization of animals with various doses of mumps virus was similar and positive responses were obtained in the absence of detectable antibodies. Even 2.5 TCID50 of mumps virus induced the response although more irregularly than 250 or 2500 TCID50 virus.", "contents": "Cell- and antibody-mediated responses to measles and mumps viruses in experimental animals. Monkeys and guinea pigs were immunized with various doses of measles and mumps viruses. A cell-mediated response measured by leukocyte migration inhibition occured during the first two weeks after immunization. In case of measles virus, marked migration inhibition occurred already on the 7th day in monkeys and guinea pigs immunized with high virus doses. The response declined as early as 14 days after immunization in contrast to the group of guinea pigs inoculated with a lower virus dose. In these animals the response sustained for up to 50 days. Immunization of animals with various doses of mumps virus was similar and positive responses were obtained in the absence of detectable antibodies. Even 2.5 TCID50 of mumps virus induced the response although more irregularly than 250 or 2500 TCID50 virus."}
{"id": "PMID:27969", "title": "Morphological characteristics of the infection of animals with tick-borne encephalitis virus persisting for a long time in cell cultures.", "content": "The pathogenicity of the Soph-K strain of tick-borne encephalitis (TBE) virus produced by the persistently infected HEp-2-Soph cell culture was investigated in monkeys, white mice and hamsters. The persistent infection of this culture with TBE virus has been maintained for 17 years. The Soph-K strain was shown to retain its pathogenic properties for mice of different ages and hamsters. Morphological examinations of the brains and spinal cords of these animals infected with the Soph-K strain revealed acute and subacute forms of encephalitis. Monkeys inoculated with the Soph-K strain intracerebrally showed an asymptomatic infection with the pathomorphological picture of subacute disseminated meningoencephalitis with a progredient course for 3 months of observation. This chronic TBE infection in monkeys offers an interesting model for investigations on progressive degenerative disease of the nervous system.", "contents": "Morphological characteristics of the infection of animals with tick-borne encephalitis virus persisting for a long time in cell cultures. The pathogenicity of the Soph-K strain of tick-borne encephalitis (TBE) virus produced by the persistently infected HEp-2-Soph cell culture was investigated in monkeys, white mice and hamsters. The persistent infection of this culture with TBE virus has been maintained for 17 years. The Soph-K strain was shown to retain its pathogenic properties for mice of different ages and hamsters. Morphological examinations of the brains and spinal cords of these animals infected with the Soph-K strain revealed acute and subacute forms of encephalitis. Monkeys inoculated with the Soph-K strain intracerebrally showed an asymptomatic infection with the pathomorphological picture of subacute disseminated meningoencephalitis with a progredient course for 3 months of observation. This chronic TBE infection in monkeys offers an interesting model for investigations on progressive degenerative disease of the nervous system."}
{"id": "PMID:27970", "title": "Sepcific immunofluorescent IgG, IgM, and IgA antibodies in lymphocytic choriomeningitis.", "content": "In postnatally acquired lymphocytic choriomeningitis (LCM), specific immunofluorescent (IF) IgM antibody was found nearly in all the examined sera from 23 patients for 6-8 months after onset of the disease, IgA antibody in two-thirds of the patients and only during the first 5 weeks of the disease. In the first weeks, the titres of IF IgG and IgM antibodies reached values from 256-512 in some patients; IgA antibody titres were considerably lower. No specific IF IgM and IgA antibody was found in sera from 5 infants with prenatal LCM virus infection (3 infants with congenital hydrocephalus and chorioretinitis, 1 with cerebral palsy and chorioretinitis, and 1 with asymptomatic infection). IF IgM antibody in a titre of 4 was detected only in 2 specimens of the cerebrospinal fluid from one of the infants with hydrocephalus. It is suggested that in prenatal LCM virus infection the production of specific IgM antibody is more or less inhibited.", "contents": "Sepcific immunofluorescent IgG, IgM, and IgA antibodies in lymphocytic choriomeningitis. In postnatally acquired lymphocytic choriomeningitis (LCM), specific immunofluorescent (IF) IgM antibody was found nearly in all the examined sera from 23 patients for 6-8 months after onset of the disease, IgA antibody in two-thirds of the patients and only during the first 5 weeks of the disease. In the first weeks, the titres of IF IgG and IgM antibodies reached values from 256-512 in some patients; IgA antibody titres were considerably lower. No specific IF IgM and IgA antibody was found in sera from 5 infants with prenatal LCM virus infection (3 infants with congenital hydrocephalus and chorioretinitis, 1 with cerebral palsy and chorioretinitis, and 1 with asymptomatic infection). IF IgM antibody in a titre of 4 was detected only in 2 specimens of the cerebrospinal fluid from one of the infants with hydrocephalus. It is suggested that in prenatal LCM virus infection the production of specific IgM antibody is more or less inhibited."}
{"id": "PMID:27972", "title": "Accurate determination of volumes injected intracerebrally into suckling mice.", "content": "Inoculum with 125I added as a marker was used to determine the volume actually administered to suckling mice on intracerebral (i.c.) inoculation. In 1-2 days old animals, this volume corresponded to approximately 75% of a 20 microliter dose.", "contents": "Accurate determination of volumes injected intracerebrally into suckling mice. Inoculum with 125I added as a marker was used to determine the volume actually administered to suckling mice on intracerebral (i.c.) inoculation. In 1-2 days old animals, this volume corresponded to approximately 75% of a 20 microliter dose."}
{"id": "PMID:27973", "title": "Effect of interferon and poly I:C on replication of influenza virus in organ cultures of human origin.", "content": "Interferon and poly I : C inhibited the growth of influenza virus in organ cultures of foetal nasal mucosa, trachea, oesophagus and adult nasal mucosa. No antiviral effect was observed in decidua organ cultures. The combined use of interferon and poly I : C resulted in the enhancement of the antiviral effect.", "contents": "Effect of interferon and poly I:C on replication of influenza virus in organ cultures of human origin. Interferon and poly I : C inhibited the growth of influenza virus in organ cultures of foetal nasal mucosa, trachea, oesophagus and adult nasal mucosa. No antiviral effect was observed in decidua organ cultures. The combined use of interferon and poly I : C resulted in the enhancement of the antiviral effect."}
{"id": "PMID:27974", "title": "Quantitative immunoelectrophoresis of human interferon. A new approach to characterization of interferon preparations.", "content": "The electroimmunoassay (quantitative \"rocket\" immunoelectrophoresis) method was adopted for analysis and characterization of interferon preparations. Ammonium sulphate-precipitated anti-interferon globulin also containing unknown antibodies against antigens that contaminate interferon preparations was used in the tests. By comparing the results of the electroimmunoassay of fractions obtained by polyacrylamide gel electrophoresis of human leukocyte interferon with the antiviral activity of the fractions, an excellent dissociation of molecules with interferon activity from the bulk of contaminating antigens was achieved. The method is extremely sensitive and requires very small volumes for assay.", "contents": "Quantitative immunoelectrophoresis of human interferon. A new approach to characterization of interferon preparations. The electroimmunoassay (quantitative \"rocket\" immunoelectrophoresis) method was adopted for analysis and characterization of interferon preparations. Ammonium sulphate-precipitated anti-interferon globulin also containing unknown antibodies against antigens that contaminate interferon preparations was used in the tests. By comparing the results of the electroimmunoassay of fractions obtained by polyacrylamide gel electrophoresis of human leukocyte interferon with the antiviral activity of the fractions, an excellent dissociation of molecules with interferon activity from the bulk of contaminating antigens was achieved. The method is extremely sensitive and requires very small volumes for assay."}
{"id": "PMID:27975", "title": "Transmission of Kyasanur Forest disease virus by Rhipicephalus haemaphysaloides ticks.", "content": "Larvae of Rhipicephalus haemaphysaloides were infected with Kaysanur Forest disease (KFD) virus by feeding on viraemic rodents and reared into next generation larvae. Fed larvae, nymphs, unfed adults, fed adult males, and females after oviposition were found infected, while the larvae were found free from infection. Nymphs and adults transmitted the infection by bite to rodents and rabbits respectively. The virus was also passed through a second rodent-tick cycle. Adult ticks showed a titre of 3.1 to 4.5 dex mouse LD50/0.03 ml, and the virus was also detected 245 days after infection.", "contents": "Transmission of Kyasanur Forest disease virus by Rhipicephalus haemaphysaloides ticks. Larvae of Rhipicephalus haemaphysaloides were infected with Kaysanur Forest disease (KFD) virus by feeding on viraemic rodents and reared into next generation larvae. Fed larvae, nymphs, unfed adults, fed adult males, and females after oviposition were found infected, while the larvae were found free from infection. Nymphs and adults transmitted the infection by bite to rodents and rabbits respectively. The virus was also passed through a second rodent-tick cycle. Adult ticks showed a titre of 3.1 to 4.5 dex mouse LD50/0.03 ml, and the virus was also detected 245 days after infection."}
{"id": "PMID:27976", "title": "Failure of 5-bromodeoxyuridine to influence the activation of latent herpex simplex virus infection in explants of the rabbit regional sensory ganglia.", "content": "The occurence of virus-specific antigens in explants of the Gasserian ganglia of rabbits with healed keratitis induced by the Kupka strain of human herpesvirus type 1 was tested by indirect immunofluorescence. In explants, the neurons and satellite cells revealed specific fluorescence from the 3rd day of culturing. The pattern of virus activation in the ganglion tissue was similar irrespective of whether the explants were cultured in the presence or absence of 5-bromo-2'-deoxyuridine.", "contents": "Failure of 5-bromodeoxyuridine to influence the activation of latent herpex simplex virus infection in explants of the rabbit regional sensory ganglia. The occurence of virus-specific antigens in explants of the Gasserian ganglia of rabbits with healed keratitis induced by the Kupka strain of human herpesvirus type 1 was tested by indirect immunofluorescence. In explants, the neurons and satellite cells revealed specific fluorescence from the 3rd day of culturing. The pattern of virus activation in the ganglion tissue was similar irrespective of whether the explants were cultured in the presence or absence of 5-bromo-2'-deoxyuridine."}
{"id": "PMID:27977", "title": "Khasan virus, a new ungrouped bunyavirus isolated from Haemaphysalis longicornis ticks in the Primorie region.", "content": "Strain LEIV-776P, possessing no haemagglutinating activity was isolated in 1971 in the Primorie region (U.S.S.R.) from Haemaphysalis longicornis Neumann 1091 tick. Complement fixation (CF) tests revealed no antigenic relationship with 24 antigenic groups of arboviruses or 21 ungrouped viruses isolated from ticks. The virus isolate contains RNA and is relatively sensitive to ether and sodium deoxycholate; it is pathogenic for suckling mice and two-week-old white mice by the intracerebral route, and replicates in primary cultures of chick and duck fibroblasts and green monkey kidneys and in a continuous line of pig embryo kidney cells without any cytopathic effect. According to electron microscopy, its size is 90-110 nm. Its morphological properties permit to classify it as a member of the family Bunyaviridae.", "contents": "Khasan virus, a new ungrouped bunyavirus isolated from Haemaphysalis longicornis ticks in the Primorie region. Strain LEIV-776P, possessing no haemagglutinating activity was isolated in 1971 in the Primorie region (U.S.S.R.) from Haemaphysalis longicornis Neumann 1091 tick. Complement fixation (CF) tests revealed no antigenic relationship with 24 antigenic groups of arboviruses or 21 ungrouped viruses isolated from ticks. The virus isolate contains RNA and is relatively sensitive to ether and sodium deoxycholate; it is pathogenic for suckling mice and two-week-old white mice by the intracerebral route, and replicates in primary cultures of chick and duck fibroblasts and green monkey kidneys and in a continuous line of pig embryo kidney cells without any cytopathic effect. According to electron microscopy, its size is 90-110 nm. Its morphological properties permit to classify it as a member of the family Bunyaviridae."}
{"id": "PMID:27980", "title": "Correlation between foetal pH, cord blood glucose level and Apgar score in a foetal intensive care unit--preliminary report.", "content": "The foetal pH (the term 'foetal pH' is used for the pH of foetal capillary blood obtained by making a small incision in the foetal scalp or buttocks) and the umbilical cord blood glucose levels in pregnant women with foetal distress were estimated in 19 babies as a prospective study in Ile-Ife, Nigeria. The Apgar Scores on delivery were also estimated. There was a significant correlation coefficient between foetal pH and Apgar Score r = 0.38 and the coefficient of correlation between umbilical artery blood glucose and foetal pH was 0.08. Estimation of the pH of blood taken from the foetal scalp is now well established as a diagnostic measure in the early diagnosis of foetal distress due to hypoxia. The results obtained from this small series of nineteen patients highlights the importance of the estimation of foetal pH, blood glucose and the Apgar Score. This is the first account in Ile-Ife, Nigeria.", "contents": "Correlation between foetal pH, cord blood glucose level and Apgar score in a foetal intensive care unit--preliminary report. The foetal pH (the term 'foetal pH' is used for the pH of foetal capillary blood obtained by making a small incision in the foetal scalp or buttocks) and the umbilical cord blood glucose levels in pregnant women with foetal distress were estimated in 19 babies as a prospective study in Ile-Ife, Nigeria. The Apgar Scores on delivery were also estimated. There was a significant correlation coefficient between foetal pH and Apgar Score r = 0.38 and the coefficient of correlation between umbilical artery blood glucose and foetal pH was 0.08. Estimation of the pH of blood taken from the foetal scalp is now well established as a diagnostic measure in the early diagnosis of foetal distress due to hypoxia. The results obtained from this small series of nineteen patients highlights the importance of the estimation of foetal pH, blood glucose and the Apgar Score. This is the first account in Ile-Ife, Nigeria."}
{"id": "PMID:27982", "title": "Adjunctive drug use by methadone patients.", "content": "Clinical impressions, reinforced by reports in both professional journals and the lay press, suggested that use and abuse of minor tranquilizers and sedative-hypnotics was extensive among patients in our drug treatment clinics and required some change in our policies. We surveyed a randomly selected national sample of methadone program physicians and found they shared our assumptions concerning the use of these drugs. A pilot program of urine screening for the presence of adjunctive drugs was completed, and we found the incidence of use to be below expected levels, except for opiates and alcohol. These results suggest we should reconsider plans to alter clinic policies concerning the regulation of these substances. A rigorous examination of serum and/or urine in a national research program to determine both the incidence of adjunctive drug use by clients in drug treatment programs and correlations of such data with national surveys would be an expensive undertaking, but would provide a more rational basis for policy making at both local and national levels.", "contents": "Adjunctive drug use by methadone patients. Clinical impressions, reinforced by reports in both professional journals and the lay press, suggested that use and abuse of minor tranquilizers and sedative-hypnotics was extensive among patients in our drug treatment clinics and required some change in our policies. We surveyed a randomly selected national sample of methadone program physicians and found they shared our assumptions concerning the use of these drugs. A pilot program of urine screening for the presence of adjunctive drugs was completed, and we found the incidence of use to be below expected levels, except for opiates and alcohol. These results suggest we should reconsider plans to alter clinic policies concerning the regulation of these substances. A rigorous examination of serum and/or urine in a national research program to determine both the incidence of adjunctive drug use by clients in drug treatment programs and correlations of such data with national surveys would be an expensive undertaking, but would provide a more rational basis for policy making at both local and national levels."}
{"id": "PMID:27983", "title": "Esophageal epithelial response to gastroesophageal reflux. A quantitative study.", "content": "Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papillae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux.", "contents": "Esophageal epithelial response to gastroesophageal reflux. A quantitative study. Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papillae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux."}
{"id": "PMID:27984", "title": "NADPH-oxidation activities in subcellular fractions isolated from resting or phagocytozing human polymorphonuclears.", "content": "Using a fluorometric assay for the determination of oxidized pyridine nucleotides (NAD[P]+), total and cyanide-resistant NADPH-oxidative activities have been measured in subcellular fractions isolated from resting and phagocytosing human polymorphonuclears. Enzymatic activies responsible for the oxidation of the NADPH have been recovered in the heavy particles (15,000g/15 min), the low-density particles (100,000g/30 min), and the cytosolic fraction. Stimulation of the cells with opsonized zymosan had a different effect on the NADPH-oxidative activities of these subcellular fractions, which suggests the involvement of various types of enzymatic systems in the oxidation of NADPH. The cytosolic fraction interacted strongly with the enzymatic activities occurring in the sedimentable fractions and is therefore thought to play a central role in the regulation of the activation of the oxidative metabolism associated with phagocytosis.", "contents": "NADPH-oxidation activities in subcellular fractions isolated from resting or phagocytozing human polymorphonuclears. Using a fluorometric assay for the determination of oxidized pyridine nucleotides (NAD[P]+), total and cyanide-resistant NADPH-oxidative activities have been measured in subcellular fractions isolated from resting and phagocytosing human polymorphonuclears. Enzymatic activies responsible for the oxidation of the NADPH have been recovered in the heavy particles (15,000g/15 min), the low-density particles (100,000g/30 min), and the cytosolic fraction. Stimulation of the cells with opsonized zymosan had a different effect on the NADPH-oxidative activities of these subcellular fractions, which suggests the involvement of various types of enzymatic systems in the oxidation of NADPH. The cytosolic fraction interacted strongly with the enzymatic activities occurring in the sedimentable fractions and is therefore thought to play a central role in the regulation of the activation of the oxidative metabolism associated with phagocytosis."}
{"id": "PMID:27985", "title": "Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts.", "content": "Multiple deficiency disorder fibroblasts cultured in MEM-CO2 showed deficiencies of arylsulfatase A(ARS A) comparable to the deficiency in metachromatic leukodystrophy fibroblasts. However, the MSDD fibroblasts cultured in MEM-HEPES contained near normal levels of ARS A. Moreover, the enzyme from the latter fibroblasts was indistinguishable from ARS A of control fibroblasts on DEAE-cellulose chromatography, ratio of activity with several substrates, thermal inactivation, sensitivity to inhibitors, and precipitation by antiserum to human ARS A. These data support the conclusion that the ARS A genome is intact in MSDD fibroblasts and, by extension, in MSDD patients. Other sulfatases were present at levels ranging from mildly deficient to near normal but never as low as seen in the corresponding specific sulfatase deficient disorders.", "contents": "Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts. Multiple deficiency disorder fibroblasts cultured in MEM-CO2 showed deficiencies of arylsulfatase A(ARS A) comparable to the deficiency in metachromatic leukodystrophy fibroblasts. However, the MSDD fibroblasts cultured in MEM-HEPES contained near normal levels of ARS A. Moreover, the enzyme from the latter fibroblasts was indistinguishable from ARS A of control fibroblasts on DEAE-cellulose chromatography, ratio of activity with several substrates, thermal inactivation, sensitivity to inhibitors, and precipitation by antiserum to human ARS A. These data support the conclusion that the ARS A genome is intact in MSDD fibroblasts and, by extension, in MSDD patients. Other sulfatases were present at levels ranging from mildly deficient to near normal but never as low as seen in the corresponding specific sulfatase deficient disorders."}
{"id": "PMID:27986", "title": "Renal response of fetal lamb to complete occlusion of umbilical cord.", "content": "The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure.", "contents": "Renal response of fetal lamb to complete occlusion of umbilical cord. The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure."}
{"id": "PMID:27988", "title": "Effects of pH, Ca, ADH, and theophylline on kinetics of Na entry in frog skin.", "content": "The short circuit current as a function of Na concentration in both solutions was found to obey Michaelis-Menten kinetics under a variety of experimental conditions. Values of maximal transport rate (Im) and half-maximal Na concentrations (Kt) were determined from these experiments. Three type of results were obtained: 1) Im and Kt both decreased by approximately the same fraction when the pH of both solutions was reduced by increasing PCO2, 2) Im decreased and Kt increased when the external pH was decreased, and 3) Im increased with ADH and theophylline, decreased with external Ca, and Kt remained unchanged. Various criteria were utilized to determine that these were properties of the entry barrier for Na into the \"transport pool.\" The results are explained in terms of a model that separates three different types of actions on the entry barrier: 1) competition of Na with other ions in the external solution for entry, 2) modulation of the number of sites available for Na translocation by changing the cytoplasmic pH, and 3) alterations in the rate of Na translocation caused by changes in the Na permeability or the electrochemical gradient across the entry barrier.", "contents": "Effects of pH, Ca, ADH, and theophylline on kinetics of Na entry in frog skin. The short circuit current as a function of Na concentration in both solutions was found to obey Michaelis-Menten kinetics under a variety of experimental conditions. Values of maximal transport rate (Im) and half-maximal Na concentrations (Kt) were determined from these experiments. Three type of results were obtained: 1) Im and Kt both decreased by approximately the same fraction when the pH of both solutions was reduced by increasing PCO2, 2) Im decreased and Kt increased when the external pH was decreased, and 3) Im increased with ADH and theophylline, decreased with external Ca, and Kt remained unchanged. Various criteria were utilized to determine that these were properties of the entry barrier for Na into the \"transport pool.\" The results are explained in terms of a model that separates three different types of actions on the entry barrier: 1) competition of Na with other ions in the external solution for entry, 2) modulation of the number of sites available for Na translocation by changing the cytoplasmic pH, and 3) alterations in the rate of Na translocation caused by changes in the Na permeability or the electrochemical gradient across the entry barrier."}
{"id": "PMID:27989", "title": "Intracellular pH transients in rat diaphragm muscle measured with DMO.", "content": "Changes of the intracellular pH of rat diaphragm muscle were monitored at 30-min intervals with the weak acid DMO (5,5-dimethyl-2,4-oxazolidinedione). Transferring the muscle from a CO2-containing to a CO2-free solution caused intracellular pH (pHi) to rise by an average of 0.18 during the first 30 min and then to level off at a slightly lower value over the next 60-90 min. Transferring the muscle from a CO2-free to a CO2-containing solution caused pHi to fall by 0.18 during the first 30 min and then to recover by 0.05 over the next 90 min. Subsequent return to the CO2-free solution caused pHi to overshoot the control value by 0.10. Both the recovery and the overshoot can be accounted for by an acid-extruding pump. Intracellular acid loading with 118 mM DMO similarly caused pHi to fall initially, to recover slowly during the acid loading, and then to overshoot the control pHi on removal of the acid load. In the absence of HCO3-/CO2, acid extrusion was reduced by about a fifth. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) had no effect. The absence of either Na+ or Cl- from HCO3-/CO2- free solution reduced acid extrusion by about a half.", "contents": "Intracellular pH transients in rat diaphragm muscle measured with DMO. Changes of the intracellular pH of rat diaphragm muscle were monitored at 30-min intervals with the weak acid DMO (5,5-dimethyl-2,4-oxazolidinedione). Transferring the muscle from a CO2-containing to a CO2-free solution caused intracellular pH (pHi) to rise by an average of 0.18 during the first 30 min and then to level off at a slightly lower value over the next 60-90 min. Transferring the muscle from a CO2-free to a CO2-containing solution caused pHi to fall by 0.18 during the first 30 min and then to recover by 0.05 over the next 90 min. Subsequent return to the CO2-free solution caused pHi to overshoot the control value by 0.10. Both the recovery and the overshoot can be accounted for by an acid-extruding pump. Intracellular acid loading with 118 mM DMO similarly caused pHi to fall initially, to recover slowly during the acid loading, and then to overshoot the control pHi on removal of the acid load. In the absence of HCO3-/CO2, acid extrusion was reduced by about a fifth. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) had no effect. The absence of either Na+ or Cl- from HCO3-/CO2- free solution reduced acid extrusion by about a half."}
{"id": "PMID:27990", "title": "Infection rates of Aedes triseriatus following ingestion of La Crosse virus by the larvae.", "content": "Infection rates ranged from 0-2.1% in adults of Aedes triseriaus reared from groups of larvae that had ingested La Crosse (LAC) virus (Clifornia encephalitis group) at dosages of 7.0-8.3 log 10 SMICLD50/ml. Females form orally infected larvae transmitted the virus to suckling mice. Larvae that devoured carcasses of transovarially infected larvae containing 3.0 log 10 SMICLD 50/ml failed to become infected. Ingestion by larvae of infected carcasses appears, therefore, to be unimportant as a method of horizontal amplification of LAC virus.", "contents": "Infection rates of Aedes triseriatus following ingestion of La Crosse virus by the larvae. Infection rates ranged from 0-2.1% in adults of Aedes triseriaus reared from groups of larvae that had ingested La Crosse (LAC) virus (Clifornia encephalitis group) at dosages of 7.0-8.3 log 10 SMICLD50/ml. Females form orally infected larvae transmitted the virus to suckling mice. Larvae that devoured carcasses of transovarially infected larvae containing 3.0 log 10 SMICLD 50/ml failed to become infected. Ingestion by larvae of infected carcasses appears, therefore, to be unimportant as a method of horizontal amplification of LAC virus."}
{"id": "PMID:27993", "title": "[Effects of diazepam and flunitrazepam on the undesired postoperative side-effects of ketamine anaesthesia (author's transl)].", "content": "150 patients undergoing minor gynaecological procedures (curretages) were anesthetized with ketamine and either diazepam flunitrazepam or placebo in order to establish the best combination for the prevention of postoperative psychotomimetic effects. From observations, up to 24 h after operation, it was found and statistically proven that the combination of ketamine/flunitrazepam as compared to the combinations ketamine/diazepam and ketamine/placebo led to a remarkable reduction of psychotomimetic side reactions.", "contents": "[Effects of diazepam and flunitrazepam on the undesired postoperative side-effects of ketamine anaesthesia (author's transl)]. 150 patients undergoing minor gynaecological procedures (curretages) were anesthetized with ketamine and either diazepam flunitrazepam or placebo in order to establish the best combination for the prevention of postoperative psychotomimetic effects. From observations, up to 24 h after operation, it was found and statistically proven that the combination of ketamine/flunitrazepam as compared to the combinations ketamine/diazepam and ketamine/placebo led to a remarkable reduction of psychotomimetic side reactions."}
{"id": "PMID:28036", "title": "[The use of naloxone in neuroleptoanalgesia].", "content": "Naloxone was used in 20 patients divided into two series: series A consisted of 10 adults with an average age of 50.6 years (+/- 12.03) and series B 10 children with an average age of 8.5 years (+/- 5.16). Naloxone was given in the treatment of postoperative respiratory depression related to persistence of morphine impregnation, the patients having received either fentanyl (mean dose 0.04 mg/kg/h) or dextromoramide (mean dose 1.15 mg/kg/h). The mean dose of naloxone was 0.26 mg +/- 0.10, i.e. 3.9 microgram/kg in series A, and 0.13 mg +/- 0.11, i.e. 5.3 microgram/kg in series B. In both series, study of ventilatory function showed correction and stabilisation of the various parameters (F/min, Vt and V) up to 180 minutes after the injection. Recovery was rapid in both groups (7 to 10 min) and of good quality. Whilst it was accompanied in a number of cases by the recurrence of pain, the latter never required specific relief. The administration of naloxone was associated with an increase in heart rate (non-significant) at 10 min in series A and 30 min in series B. Apart an episode of nausea in one case of series A, no disagreeable side effects were observed.", "contents": "[The use of naloxone in neuroleptoanalgesia]. Naloxone was used in 20 patients divided into two series: series A consisted of 10 adults with an average age of 50.6 years (+/- 12.03) and series B 10 children with an average age of 8.5 years (+/- 5.16). Naloxone was given in the treatment of postoperative respiratory depression related to persistence of morphine impregnation, the patients having received either fentanyl (mean dose 0.04 mg/kg/h) or dextromoramide (mean dose 1.15 mg/kg/h). The mean dose of naloxone was 0.26 mg +/- 0.10, i.e. 3.9 microgram/kg in series A, and 0.13 mg +/- 0.11, i.e. 5.3 microgram/kg in series B. In both series, study of ventilatory function showed correction and stabilisation of the various parameters (F/min, Vt and V) up to 180 minutes after the injection. Recovery was rapid in both groups (7 to 10 min) and of good quality. Whilst it was accompanied in a number of cases by the recurrence of pain, the latter never required specific relief. The administration of naloxone was associated with an increase in heart rate (non-significant) at 10 min in series A and 30 min in series B. Apart an episode of nausea in one case of series A, no disagreeable side effects were observed."}
{"id": "PMID:28037", "title": "[Antagonistic effects of naloxone against morphinomimetic agents. Apropos of 10 cases in gynecologic surgery].", "content": "The object of this study was the use of naloxone to correct hypoventilation related to the use of morphinomimetics without suppressing the analgesic effect of these agents. The study involved ten patients undergoing gynaecological surgery under neuroleptanalgesia and who at the end of surgery had hypoventilation due to the use of fentanyl (average dose : 4.87 microgram/kg/h) or phenoperidine (average dose : 48.7 microgram/kg/h). Naloxone was administered intravenously in an average dose of 1.37 microgram/kg (in one or two injections) followed by an intramuscular injection of an average of 0.73 microgram/kg. Under these conditions, respiratory depression was completely corrected in all cases, the effect being durable. Good analgesia was retained and there was a normal return to consciousness without undesirable effects.", "contents": "[Antagonistic effects of naloxone against morphinomimetic agents. Apropos of 10 cases in gynecologic surgery]. The object of this study was the use of naloxone to correct hypoventilation related to the use of morphinomimetics without suppressing the analgesic effect of these agents. The study involved ten patients undergoing gynaecological surgery under neuroleptanalgesia and who at the end of surgery had hypoventilation due to the use of fentanyl (average dose : 4.87 microgram/kg/h) or phenoperidine (average dose : 48.7 microgram/kg/h). Naloxone was administered intravenously in an average dose of 1.37 microgram/kg (in one or two injections) followed by an intramuscular injection of an average of 0.73 microgram/kg. Under these conditions, respiratory depression was completely corrected in all cases, the effect being durable. Good analgesia was retained and there was a normal return to consciousness without undesirable effects."}
{"id": "PMID:28039", "title": "[Electrophysiologic aspects of the effects of etomidate in man].", "content": "Recordings were electroencephalographical (EEG with spectral analysis), polygraphical (EMG, EKG, breathing). Visual and Auditory Cerebral Evoked Responses were also recorded. The depth of narcosis was quantified upon EEG data. The reactivity during the narcosis and the mechanisms of action of Etomidate on the \"non specific structures\" are discussed. Cautions should be taken with the use of tomidate in anesthesiology with epileptic and arteriopathic patients.", "contents": "[Electrophysiologic aspects of the effects of etomidate in man]. Recordings were electroencephalographical (EEG with spectral analysis), polygraphical (EMG, EKG, breathing). Visual and Auditory Cerebral Evoked Responses were also recorded. The depth of narcosis was quantified upon EEG data. The reactivity during the narcosis and the mechanisms of action of Etomidate on the \"non specific structures\" are discussed. Cautions should be taken with the use of tomidate in anesthesiology with epileptic and arteriopathic patients."}
{"id": "PMID:28040", "title": "[Effect of etomidate on cerebral blood flow and oxygen metabolism in man].", "content": "The effects of Etomidate on cerebral blood flow (C.B.F.) and cerebral oxygen consumption (C.02 C.) were studied in 13 patients in a neuroradiology department. Induction of anaesthesia was ensured using a standard dose of 15 mg of Etomidate, followed by a constant rate infusion (2.8 mg/kg/hour). Seven subjects were considered to be normal whilst six were suffering from tumour pathology. Under the influence of Etomidate, C.B.F. in the normal subjects decreased by 34 p. 100 and C.02 C. by 46.7 p. 100. The relationship between C.B.F. and arterial PC01 was studied under the influence of Etomidate: cerebral vasoactivity to C02 was maintained. A special study was made of focal changes in flow in patients with tumour pathology. Under the influence of Etomidate, there were zones of adaptation of flow, indicative of vasoparalysis situated opposite the tumour.", "contents": "[Effect of etomidate on cerebral blood flow and oxygen metabolism in man]. The effects of Etomidate on cerebral blood flow (C.B.F.) and cerebral oxygen consumption (C.02 C.) were studied in 13 patients in a neuroradiology department. Induction of anaesthesia was ensured using a standard dose of 15 mg of Etomidate, followed by a constant rate infusion (2.8 mg/kg/hour). Seven subjects were considered to be normal whilst six were suffering from tumour pathology. Under the influence of Etomidate, C.B.F. in the normal subjects decreased by 34 p. 100 and C.02 C. by 46.7 p. 100. The relationship between C.B.F. and arterial PC01 was studied under the influence of Etomidate: cerebral vasoactivity to C02 was maintained. A special study was made of focal changes in flow in patients with tumour pathology. Under the influence of Etomidate, there were zones of adaptation of flow, indicative of vasoparalysis situated opposite the tumour."}
{"id": "PMID:28041", "title": "[Hemodynamic effects of etomidate].", "content": "A study of the haemodynamic effects of an injection of 0.3 mg/kg of Etomidate was carried out in 11 multiple trauma patients under constant controlled ventilation. At the 3 rd minute after injection there was a slight, but significant, increase in cardiac output and in the systolic index of the left ventricle, persisting at the 20th minute. It may be concluded that the injection of a dose of 0.3 mg/kg has no harmful haemodynamic effects in this type of patient.", "contents": "[Hemodynamic effects of etomidate]. A study of the haemodynamic effects of an injection of 0.3 mg/kg of Etomidate was carried out in 11 multiple trauma patients under constant controlled ventilation. At the 3 rd minute after injection there was a slight, but significant, increase in cardiac output and in the systolic index of the left ventricle, persisting at the 20th minute. It may be concluded that the injection of a dose of 0.3 mg/kg has no harmful haemodynamic effects in this type of patient."}
{"id": "PMID:28042", "title": "[Constant flow anesthesia using a combination of etomidate and fentanyl].", "content": "In 35 orthopaedic surgery patients (33 adults and 2 children), anaesthesia was obtained using an association of etomidate and fentanyl. Induction was obtained by injection from a syringe of a mixture of etomidate and fentanyl in an average dose of 21 mg for etomidate and 0,08 mg for fentanyl. Anaesthesia was maintained by constant dose of etomidate was 1.29 mg/kg/h and 4.96 microgram/kg/h for fentanyl. The mixture used for both induction and maintenance contained 1.3 mg of etomidate and 5 mg of fentanyl per ml. The results, value, indications and contraindications of this technique are described.", "contents": "[Constant flow anesthesia using a combination of etomidate and fentanyl]. In 35 orthopaedic surgery patients (33 adults and 2 children), anaesthesia was obtained using an association of etomidate and fentanyl. Induction was obtained by injection from a syringe of a mixture of etomidate and fentanyl in an average dose of 21 mg for etomidate and 0,08 mg for fentanyl. Anaesthesia was maintained by constant dose of etomidate was 1.29 mg/kg/h and 4.96 microgram/kg/h for fentanyl. The mixture used for both induction and maintenance contained 1.3 mg of etomidate and 5 mg of fentanyl per ml. The results, value, indications and contraindications of this technique are described."}
{"id": "PMID:28045", "title": "[Choice of a local anesthetic in obstetrical analgesia].", "content": "A local anaesthetic may be selected from amongst the two major groups of drugs of this type: amino-alcoyl-esters and amino-acylamides. In practice, three substances are available or will shortly be available in France: lignocaine, etidocaine and bupivacaine, thus limiting the choice. This choice is guided by the toxicity of the substance, its clinical effects and 1st side effects. 1-Toxicity depends upon the nature of the substance, the dose necessary to obtain analgesia and to prolong it for a sufficient time. 2-Amongst the clinical effects which should be noted in the choice of a local anaesthetic are the latent period before analgesia is obtained, the degree of sensory block, the degree of motor block and the duration of action. The three substances available are compared in relations to these parameters and in the light of the specific requirements of obstetric analgesia. The value of the addiction of adrenalin is discussed. 3-The side effects are those of the local anesthetic itself and of its possible association with adrenalin. On the basis of the various criteria mentioned, it would seem that the analgesic of choice for obstetric analgesia is bupivacaine used with or without adrenalin.", "contents": "[Choice of a local anesthetic in obstetrical analgesia]. A local anaesthetic may be selected from amongst the two major groups of drugs of this type: amino-alcoyl-esters and amino-acylamides. In practice, three substances are available or will shortly be available in France: lignocaine, etidocaine and bupivacaine, thus limiting the choice. This choice is guided by the toxicity of the substance, its clinical effects and 1st side effects. 1-Toxicity depends upon the nature of the substance, the dose necessary to obtain analgesia and to prolong it for a sufficient time. 2-Amongst the clinical effects which should be noted in the choice of a local anaesthetic are the latent period before analgesia is obtained, the degree of sensory block, the degree of motor block and the duration of action. The three substances available are compared in relations to these parameters and in the light of the specific requirements of obstetric analgesia. The value of the addiction of adrenalin is discussed. 3-The side effects are those of the local anesthetic itself and of its possible association with adrenalin. On the basis of the various criteria mentioned, it would seem that the analgesic of choice for obstetric analgesia is bupivacaine used with or without adrenalin."}
{"id": "PMID:28046", "title": "[Effects of peridural analgesia on labor].", "content": "A review of the effects during labour of epidural analgesia on dilatation, expulsion and delivery of the placenta. Uncertainties in knowledge of the precise organisation of uterine innervation and of the intrinsic innervation of the organ render the study of changes in uterine contraction and in cervical resistances difficult. At circulating levels higher than those found in clinical practice, local anaesthetics have a definite oxytocic e-fect, local anaesthetics have a definite oxytoci effect, whilst adrenalin is a powerfult tocolytic. By contrast, the indirect effects related to neurolysis in extradural analgesia are negligeable. Cervico-segmentary resistances are decreased. In practice, there is no increase in the period of dilatation in the absence of any haemodynamic disturbances and if mixtures containing adrenalin are avoided. Expulsion is favourised by muscular relaxation but impaired by the lack of voluntary expulsive effort, hence the choice of a local anaesthetic with the lowest possible motor effect. Delivery of the placenta, which involves only uterine contraction, which is not affected, may be accelerated by oxytocics.", "contents": "[Effects of peridural analgesia on labor]. A review of the effects during labour of epidural analgesia on dilatation, expulsion and delivery of the placenta. Uncertainties in knowledge of the precise organisation of uterine innervation and of the intrinsic innervation of the organ render the study of changes in uterine contraction and in cervical resistances difficult. At circulating levels higher than those found in clinical practice, local anaesthetics have a definite oxytocic e-fect, local anaesthetics have a definite oxytoci effect, whilst adrenalin is a powerfult tocolytic. By contrast, the indirect effects related to neurolysis in extradural analgesia are negligeable. Cervico-segmentary resistances are decreased. In practice, there is no increase in the period of dilatation in the absence of any haemodynamic disturbances and if mixtures containing adrenalin are avoided. Expulsion is favourised by muscular relaxation but impaired by the lack of voluntary expulsive effort, hence the choice of a local anaesthetic with the lowest possible motor effect. Delivery of the placenta, which involves only uterine contraction, which is not affected, may be accelerated by oxytocics."}
{"id": "PMID:28048", "title": "[The use of Marcaine in obstetrical analgesia].", "content": "Bupivacaine (Marcaine) is being used increasingly in obstetrics for epidural analgesia, by virtue of the good sensory block obtained and the minimum of side-effects on the mother and newborn infant. At a concentration of less than 0.5 p. 100, analgesia is excellent with a minimal effect on motor fibres. Side-effects and toxicity are limited by the use of fractionated doses from the beginning of labour or of a single dose during or at the end of labour calculated in relation to the effect sought. Any action on the newborn infant would appear to be exceptional, if dose recommendations are respected, the high percentage of Marcaine bound to proteins limiting its transplacental passage.", "contents": "[The use of Marcaine in obstetrical analgesia]. Bupivacaine (Marcaine) is being used increasingly in obstetrics for epidural analgesia, by virtue of the good sensory block obtained and the minimum of side-effects on the mother and newborn infant. At a concentration of less than 0.5 p. 100, analgesia is excellent with a minimal effect on motor fibres. Side-effects and toxicity are limited by the use of fractionated doses from the beginning of labour or of a single dose during or at the end of labour calculated in relation to the effect sought. Any action on the newborn infant would appear to be exceptional, if dose recommendations are respected, the high percentage of Marcaine bound to proteins limiting its transplacental passage."}
{"id": "PMID:28049", "title": "[Experience of labor and obstetrical analgesia].", "content": "A prospective study was undertaken at Strasbourg of the assessment of the patients of the techniques used by the obstetric team and of the general atmosphere in which labour and delivery took place. A questionnair of 115 items was analysed by computer using a Pastis-Pascal programme (see attached). The first results, concerning the analysis of 100 cases and taking into account approximately ten variables, gave the following findings: -the intolerable pain factor is related to the period of dilatation; -the analgesic or amnesic factor in the mother influences the satisfaction she experiences in relation to her child; -demand for epidural anaesthesia appeared the same, whether the woman had been prepared by a psychoprophylactic method or not; -psychoprophylactic preparation would not appear to influence the assessment of pain; -women having an epidural anaesthetic never considered their labour to have been intolerable. Discriminant analysis with study of correlations is not possible at present. Given the number of variables to be considered, the population analysed is inadequate. A multicentre study would improve the performance of this research. Our questionnaire is available to any teams who might wish to use it.", "contents": "[Experience of labor and obstetrical analgesia]. A prospective study was undertaken at Strasbourg of the assessment of the patients of the techniques used by the obstetric team and of the general atmosphere in which labour and delivery took place. A questionnair of 115 items was analysed by computer using a Pastis-Pascal programme (see attached). The first results, concerning the analysis of 100 cases and taking into account approximately ten variables, gave the following findings: -the intolerable pain factor is related to the period of dilatation; -the analgesic or amnesic factor in the mother influences the satisfaction she experiences in relation to her child; -demand for epidural anaesthesia appeared the same, whether the woman had been prepared by a psychoprophylactic method or not; -psychoprophylactic preparation would not appear to influence the assessment of pain; -women having an epidural anaesthetic never considered their labour to have been intolerable. Discriminant analysis with study of correlations is not possible at present. Given the number of variables to be considered, the population analysed is inadequate. A multicentre study would improve the performance of this research. Our questionnaire is available to any teams who might wish to use it."}
{"id": "PMID:28050", "title": "[The organization of an obstetric center in relation to obstetrical analgesia].", "content": "In order that continous epidural anaesthesia may be given safely in an obstetric centre, the permanent presence of an anaesthetist is necessary. Obstetricians and midwives must be familiar with the management of labour using this method and team spirit involving continous cooperation between the anaesthetist, obstetrician and midwives is essential. Training related to epidural anaesthesia is necessary  for the members of the obsteric centre, as well as education of the patients.", "contents": "[The organization of an obstetric center in relation to obstetrical analgesia]. In order that continous epidural anaesthesia may be given safely in an obstetric centre, the permanent presence of an anaesthetist is necessary. Obstetricians and midwives must be familiar with the management of labour using this method and team spirit involving continous cooperation between the anaesthetist, obstetrician and midwives is essential. Training related to epidural anaesthesia is necessary  for the members of the obsteric centre, as well as education of the patients."}
{"id": "PMID:28051", "title": "[Economic and social problems posed by peridural anesthesia and obstetrical analgesia].", "content": "It is impossible not to note the small number of epidural anaesthetics given for obstetrics in France. The rarity of centres where it is offered by a team of specially trained anaesthetists and obstetricians contrasts with the increase in demand from the patients themselves. Study of the number of epidural anaesthetics predictable in obstetrics according to the criteria of indication indicates that the procedure could be used in as many as 30 to 50 per cent of deliveries. This implies a need for an increase in the number of anaesthetists, i.e. an increase not so much in the total number as in those trained in obstetrics with experience of epidural anaesthesia. Similar changes are necessary in hospital organisation, in such a way that the place of the anaesthetist in the maternity unit is recognised officially, this recognition being strengthened by routine out-patient consultation with all patients during their pregnancy. The economic aspect of a possible increase in the number of epidural anaesthetics carried out in France and in the number of anaesthetists performing the procedure is envisaged in terms of salaries in the public hospital system, costing of the procedure by the Social Security and the true cost of epidural anaesthesia.", "contents": "[Economic and social problems posed by peridural anesthesia and obstetrical analgesia]. It is impossible not to note the small number of epidural anaesthetics given for obstetrics in France. The rarity of centres where it is offered by a team of specially trained anaesthetists and obstetricians contrasts with the increase in demand from the patients themselves. Study of the number of epidural anaesthetics predictable in obstetrics according to the criteria of indication indicates that the procedure could be used in as many as 30 to 50 per cent of deliveries. This implies a need for an increase in the number of anaesthetists, i.e. an increase not so much in the total number as in those trained in obstetrics with experience of epidural anaesthesia. Similar changes are necessary in hospital organisation, in such a way that the place of the anaesthetist in the maternity unit is recognised officially, this recognition being strengthened by routine out-patient consultation with all patients during their pregnancy. The economic aspect of a possible increase in the number of epidural anaesthetics carried out in France and in the number of anaesthetists performing the procedure is envisaged in terms of salaries in the public hospital system, costing of the procedure by the Social Security and the true cost of epidural anaesthesia."}
{"id": "PMID:28052", "title": "[Study of a new respiratory analeptic: injectable almatrine. Apropos of 22 cases of acute hypoventilation: respiratory activity and electroencephalographic control].", "content": "2620 is a respiratory analeptic which acts by stimulation of peripheral chemoreceptors. It was administered intravenously in 22 patients in acute respiratory insufficiency. Doses during the first hour varied between 0.7 and 3 mg/kg. A careful study of the effects on respiration showed a significant increase in minute ventilation without any proportional increase in frequency for doses of between 1.7 and 3 mg/kg. Continuous recording of the electroencephalogram over a period of one hour revealed no convulsant effect even in particularly vulnerable patients. In seven patients, tracings showed a change in the sense of increased consciousness which corresponded with the clinical course of the diseases responsible for the state of hypoventilation.", "contents": "[Study of a new respiratory analeptic: injectable almatrine. Apropos of 22 cases of acute hypoventilation: respiratory activity and electroencephalographic control]. 2620 is a respiratory analeptic which acts by stimulation of peripheral chemoreceptors. It was administered intravenously in 22 patients in acute respiratory insufficiency. Doses during the first hour varied between 0.7 and 3 mg/kg. A careful study of the effects on respiration showed a significant increase in minute ventilation without any proportional increase in frequency for doses of between 1.7 and 3 mg/kg. Continuous recording of the electroencephalogram over a period of one hour revealed no convulsant effect even in particularly vulnerable patients. In seven patients, tracings showed a change in the sense of increased consciousness which corresponded with the clinical course of the diseases responsible for the state of hypoventilation."}
{"id": "PMID:28053", "title": "[Apropos of complications following the use of methylmethacrylate. Possible prevention by betamethasone].", "content": "The aim of this study was to determine whether the prior injection of betamethasone was capable of preventing blood pressure changes and the fall in arterial pO2 when following the fixation of total hip protheses with methyl metacrylate. It involved 54 patients in whom systolic, diastolic and mean blood pressure (BP), arterial pO2, pCO2 and heart rate were noted at different times: T1, 15 minutes after the beginning of the operation; T2 and T3, one minute and five minutes after application of the cement; T4, at the end of the operation. There was no significant difference between the various measurements at times T1, T2, and T3 as far as blood pressure and heart rate were concerned. By contrast, there was a fall in pO2 at times T2 and T2 in relation to times T1 and T4. This fall was significant (p is less than 0.01) but never theless remained moderate. The possible influence of betamethasone is discussed.", "contents": "[Apropos of complications following the use of methylmethacrylate. Possible prevention by betamethasone]. The aim of this study was to determine whether the prior injection of betamethasone was capable of preventing blood pressure changes and the fall in arterial pO2 when following the fixation of total hip protheses with methyl metacrylate. It involved 54 patients in whom systolic, diastolic and mean blood pressure (BP), arterial pO2, pCO2 and heart rate were noted at different times: T1, 15 minutes after the beginning of the operation; T2 and T3, one minute and five minutes after application of the cement; T4, at the end of the operation. There was no significant difference between the various measurements at times T1, T2, and T3 as far as blood pressure and heart rate were concerned. By contrast, there was a fall in pO2 at times T2 and T2 in relation to times T1 and T4. This fall was significant (p is less than 0.01) but never theless remained moderate. The possible influence of betamethasone is discussed."}
{"id": "PMID:28054", "title": "[Comparative study of venous contamination with low FiO2 and with pure oxygen in disease-induced pulmonary edema].", "content": "A comparative study of the venous contamination (Qs/Qt = (Cc'O2 - CaO2) / (Cc'O2 - C-vO2) under FIO2 = 0.45 - 0.6 and under FIO2 = 1, was realised in 9 patients with lesions of pulmonary oedema. Increasing the FIO2 lead to an increase in the venous contamination three times (average increase was 36 p. 100 of the initial value), to no change two times and a decrease four times (average decrease of 34 p. 100). The values of the venous contamination under average FIO2 are statistically lower in the group where it rises on increasing the FIO2 than in that in which it falls or remains unchanged (p is less than 0.005).", "contents": "[Comparative study of venous contamination with low FiO2 and with pure oxygen in disease-induced pulmonary edema]. A comparative study of the venous contamination (Qs/Qt = (Cc'O2 - CaO2) / (Cc'O2 - C-vO2) under FIO2 = 0.45 - 0.6 and under FIO2 = 1, was realised in 9 patients with lesions of pulmonary oedema. Increasing the FIO2 lead to an increase in the venous contamination three times (average increase was 36 p. 100 of the initial value), to no change two times and a decrease four times (average decrease of 34 p. 100). The values of the venous contamination under average FIO2 are statistically lower in the group where it rises on increasing the FIO2 than in that in which it falls or remains unchanged (p is less than 0.005)."}
{"id": "PMID:28055", "title": "[Biological tests as indirect indicators of the activity of drug metabolizing enzymes. Use of glucaric acid and gamma-glutamyltransferase].", "content": "Laboratory tests are increasingly important in the surveillance of drug treatments. People in charge of clinical laboratory science must now become aware of a new development, the use of as indicators of the activity of drug-metabolizing enzymes, especially of the induction of such enzymes. Ideally, the activity of such enzymes should be measured in the tissues. In man, however, easier indirect methods of application are now most often used : measurement of antipyrine half-life, urinary and plasma drug metabolites, protein and specific enzyme levels in palsma, changes in endogenous substrates and endogenous metabolites, and enzymes in circulating blood cells. Of all these, two examinations are now widely performed, those for urinary glucaric acid and gamma-glutamyltrasferase. The value and limitations of these two tests are discussed.", "contents": "[Biological tests as indirect indicators of the activity of drug metabolizing enzymes. Use of glucaric acid and gamma-glutamyltransferase]. Laboratory tests are increasingly important in the surveillance of drug treatments. People in charge of clinical laboratory science must now become aware of a new development, the use of as indicators of the activity of drug-metabolizing enzymes, especially of the induction of such enzymes. Ideally, the activity of such enzymes should be measured in the tissues. In man, however, easier indirect methods of application are now most often used : measurement of antipyrine half-life, urinary and plasma drug metabolites, protein and specific enzyme levels in palsma, changes in endogenous substrates and endogenous metabolites, and enzymes in circulating blood cells. Of all these, two examinations are now widely performed, those for urinary glucaric acid and gamma-glutamyltrasferase. The value and limitations of these two tests are discussed."}
{"id": "PMID:28056", "title": "[Gamma-glutamyltransferase. Human pathology and animal biology].", "content": "Gamma-glutamyltransferase (GGT, EC 2.3.2.2) is in man and animals mainly a renal enzyme. It is also present in non-negligeable quantities in the liver except in certain rodents such as the rat. In the cells, the cytosoluble fraction of the enzyme is very low and most of the enzyme is linked to the microsomal fraction in vitro. This fraction permits its use in the diagnosis of liver and biliary disease by measurement of its serum activity and that of renal disease by measurement of its urinary activity. In biological research, the prospects offered by GGT both in human and animal cancers, and in pharmacology and toxicology makes it probably one of the most appreciated biological tests in the exploration of liver, biliary and renal function.", "contents": "[Gamma-glutamyltransferase. Human pathology and animal biology]. Gamma-glutamyltransferase (GGT, EC 2.3.2.2) is in man and animals mainly a renal enzyme. It is also present in non-negligeable quantities in the liver except in certain rodents such as the rat. In the cells, the cytosoluble fraction of the enzyme is very low and most of the enzyme is linked to the microsomal fraction in vitro. This fraction permits its use in the diagnosis of liver and biliary disease by measurement of its serum activity and that of renal disease by measurement of its urinary activity. In biological research, the prospects offered by GGT both in human and animal cancers, and in pharmacology and toxicology makes it probably one of the most appreciated biological tests in the exploration of liver, biliary and renal function."}
{"id": "PMID:28057", "title": "[Neutral leucinamidasic activity of human serum. Semiautomatic method of analysis].", "content": "Half automated method for determining a L-leucinamide splitting enzymatic activity in human sera. In normal and pathological human sera, two distinct L-leucinamide splitting enzymatic activities have been demonstrated. One of them has an optimal activity at pH 9 (alcaline leucine amidase activity) and shows the most properties of a classic leucinaminopeptidase (E.C. 3.4.11.1). The other (neutral leucine amidase activity) has an optimal activity at pH : 7,5--7,8 and is not activated by Mg2+ ions. In the present work a semi-automated method permitting the determination of the \"neutral leucine amidase activity\" is presented. The mean of the reference values for normal human sera are established to 31,54 mUI/ml, and the upper normal limit is 48 mUI/ml. The neutral leucine amidase activity is studied in pathological sera comparatively with two other aminopeptidase activities : \"alcaline leucine amidase activity\", and \"leucine-arylamidase\". Our study shows that in pathological sera, the neutral leucine amidase activity\" varies often without any correlation with those parameters.", "contents": "[Neutral leucinamidasic activity of human serum. Semiautomatic method of analysis]. Half automated method for determining a L-leucinamide splitting enzymatic activity in human sera. In normal and pathological human sera, two distinct L-leucinamide splitting enzymatic activities have been demonstrated. One of them has an optimal activity at pH 9 (alcaline leucine amidase activity) and shows the most properties of a classic leucinaminopeptidase (E.C. 3.4.11.1). The other (neutral leucine amidase activity) has an optimal activity at pH : 7,5--7,8 and is not activated by Mg2+ ions. In the present work a semi-automated method permitting the determination of the \"neutral leucine amidase activity\" is presented. The mean of the reference values for normal human sera are established to 31,54 mUI/ml, and the upper normal limit is 48 mUI/ml. The neutral leucine amidase activity is studied in pathological sera comparatively with two other aminopeptidase activities : \"alcaline leucine amidase activity\", and \"leucine-arylamidase\". Our study shows that in pathological sera, the neutral leucine amidase activity\" varies often without any correlation with those parameters."}
{"id": "PMID:28058", "title": "Safety of therapy for allergic symptoms during pregnancy.", "content": "We undertook a literature review to document whether certain therapeutic measures could be considered safe during pregnancy in the allergic patient. With the possible exception of brompheniramine, the commonly used antihistamine drugs appear to be safe during pregnancy. The bronchodilators ephedrine and theophylline also appear to be safe, as does cromolyn. Corticosteroids do not appear to have adverse effects in pregnancy beyond those well recognized in nonpregnant patients. Because side effects are reduced when steroids are administered as aerosols in the nose or lung, these preparations seem well suited for use in pregnancy. The safety of allergic immunotherapy has been confirmed. For asthma, annual influenza vaccination is indicated.", "contents": "Safety of therapy for allergic symptoms during pregnancy. We undertook a literature review to document whether certain therapeutic measures could be considered safe during pregnancy in the allergic patient. With the possible exception of brompheniramine, the commonly used antihistamine drugs appear to be safe during pregnancy. The bronchodilators ephedrine and theophylline also appear to be safe, as does cromolyn. Corticosteroids do not appear to have adverse effects in pregnancy beyond those well recognized in nonpregnant patients. Because side effects are reduced when steroids are administered as aerosols in the nose or lung, these preparations seem well suited for use in pregnancy. The safety of allergic immunotherapy has been confirmed. For asthma, annual influenza vaccination is indicated."}
{"id": "PMID:28059", "title": "Bilateral central retinal artery occlusions in polyarteritis nodosa.", "content": "The third reported case of bilateral central retinal artery occlusion associated with polyarteritis nodosa is presented. An alternative etiology of the frequently observed association of polyarteritis nodosa with optic atrophy is suggested. A plan of therapy is recommended.", "contents": "Bilateral central retinal artery occlusions in polyarteritis nodosa. The third reported case of bilateral central retinal artery occlusion associated with polyarteritis nodosa is presented. An alternative etiology of the frequently observed association of polyarteritis nodosa with optic atrophy is suggested. A plan of therapy is recommended."}
{"id": "PMID:28061", "title": "beta-Blockers and the eye: an overview.", "content": "Some beta-adrenoceptor blocking drugs are exciting new ocular hypotensive compounds. Unlike pilocarpine, the mainstay of glaucoma treatment for the last 100 years, beta-blocking agents do not contract the pupil nor interfere with vision even in patients with central lens opacities. They also do not cause spasm of the ciliary muscle producing transient myopia and disturbance of accommodation. Paradoxically, one of these agents, timolol, causes a fall in intraocular pressure when administered locally even in patients responding to beta-agonists with a reduction in intraocular pressure. Concomitant administration of timolol with epinephrine seems to enhance its ocular hypotensive effect in many patients. The exact mode of action of beta-blockers in reducing intraocular pressure is unknown but appears to primarily reduce aqueous production. This new class of drugs seems destined to play an important role in the treatment as well as in the understanding of glaucoma.", "contents": "beta-Blockers and the eye: an overview. Some beta-adrenoceptor blocking drugs are exciting new ocular hypotensive compounds. Unlike pilocarpine, the mainstay of glaucoma treatment for the last 100 years, beta-blocking agents do not contract the pupil nor interfere with vision even in patients with central lens opacities. They also do not cause spasm of the ciliary muscle producing transient myopia and disturbance of accommodation. Paradoxically, one of these agents, timolol, causes a fall in intraocular pressure when administered locally even in patients responding to beta-agonists with a reduction in intraocular pressure. Concomitant administration of timolol with epinephrine seems to enhance its ocular hypotensive effect in many patients. The exact mode of action of beta-blockers in reducing intraocular pressure is unknown but appears to primarily reduce aqueous production. This new class of drugs seems destined to play an important role in the treatment as well as in the understanding of glaucoma."}
{"id": "PMID:28065", "title": "Athlete exertion injuries.", "content": "Over a period of three years 829 cases of greater than or equal to 16-year-old athlete exertion injuries and syndromes were collected. There were 75 women and 754 men in the series. About 90% of the athletes had been training regularly for more than two years, and 75% of them trained 6 times a week or more. Approximately 52% of the injuries occurred in track and field athletics, about 17% in ball events, 13.6% in skiing, 7.4% in orienteering, and 4.7% in power events. Other sports were associated with fewer exertion injuries. 28.7% of the conditions occurred in the knee, 17% in the ankle, foot and heel, 14.8% in the leg, 8.2% in the back and trunk, 8.1% in the thigh, 7.4% in the achilles tendon. The rest were in the shoulder, neck and upper extremities. In 92% of the patients conservative treatment and rest were used. Only 8% of the cases were treated surgically.", "contents": "Athlete exertion injuries. Over a period of three years 829 cases of greater than or equal to 16-year-old athlete exertion injuries and syndromes were collected. There were 75 women and 754 men in the series. About 90% of the athletes had been training regularly for more than two years, and 75% of them trained 6 times a week or more. Approximately 52% of the injuries occurred in track and field athletics, about 17% in ball events, 13.6% in skiing, 7.4% in orienteering, and 4.7% in power events. Other sports were associated with fewer exertion injuries. 28.7% of the conditions occurred in the knee, 17% in the ankle, foot and heel, 14.8% in the leg, 8.2% in the back and trunk, 8.1% in the thigh, 7.4% in the achilles tendon. The rest were in the shoulder, neck and upper extremities. In 92% of the patients conservative treatment and rest were used. Only 8% of the cases were treated surgically."}
{"id": "PMID:28066", "title": "A short review of techniques for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis.", "content": "The development of a sensitive method for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis on various media is described. Recommendations on final conditions are given for optimal concentrations of substrate, acceptor and buffer, and for pH of the reaction mixture. The reaction conditions are compared with other isoenzyme localisation techniques previously reported.", "contents": "A short review of techniques for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis. The development of a sensitive method for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis on various media is described. Recommendations on final conditions are given for optimal concentrations of substrate, acceptor and buffer, and for pH of the reaction mixture. The reaction conditions are compared with other isoenzyme localisation techniques previously reported."}
{"id": "PMID:28067", "title": "Butanol extraction of serum and urinary gamma-glutamyltransferase and its application in clinical diagnosis.", "content": "Gamma-glutamyltransferase (gamma-GT) activity was measured in serum and urine before and after extraction with n-butanol. Residual gamma-GT activity after extraction of normal serum with butanol was more than 75%, whereas for normal urine the figure was less than 68%. The loss of activity from urine was not affected by prior dialysis, and the stabilisation which resulted from adding bovine serum albumin at a concentration of 40 g/l did not approach the residual activity with normal serum. In patients with a variety of renal diseases, residual gamma-GT activity in the urine after butanol extraction was inversely correlated with the creatinine clearance. Butanol extraction was performed on serum samples from 182 patients with a variety of diseases. Eighty-one per cent of patients with elevated gamma-GT activities caused by hepatobiliary disease had an increased loss of activity after butanol extraction. By contrast, only 34% of patients with increases gamma-GT activities in whom there was no clinical or other biochemical evidence of hepatic disease, had increased loss of gamma-GT activity after butanol. The reasons for differences between urinary and serum gamma-GT in response to butanol, and the implications in interpreting serum gamma-GT activities are discussed.", "contents": "Butanol extraction of serum and urinary gamma-glutamyltransferase and its application in clinical diagnosis. Gamma-glutamyltransferase (gamma-GT) activity was measured in serum and urine before and after extraction with n-butanol. Residual gamma-GT activity after extraction of normal serum with butanol was more than 75%, whereas for normal urine the figure was less than 68%. The loss of activity from urine was not affected by prior dialysis, and the stabilisation which resulted from adding bovine serum albumin at a concentration of 40 g/l did not approach the residual activity with normal serum. In patients with a variety of renal diseases, residual gamma-GT activity in the urine after butanol extraction was inversely correlated with the creatinine clearance. Butanol extraction was performed on serum samples from 182 patients with a variety of diseases. Eighty-one per cent of patients with elevated gamma-GT activities caused by hepatobiliary disease had an increased loss of activity after butanol extraction. By contrast, only 34% of patients with increases gamma-GT activities in whom there was no clinical or other biochemical evidence of hepatic disease, had increased loss of gamma-GT activity after butanol. The reasons for differences between urinary and serum gamma-GT in response to butanol, and the implications in interpreting serum gamma-GT activities are discussed."}
{"id": "PMID:28068", "title": "Anomalous behaviour of control sera in automated versions of the Kind and King alkaline phosphatase method.", "content": "Differences in alkaline phosphatase activity of some commerical control sera were observed when comparing manual with AutoAnalyzer versions of the Kind and King procedure. This phenomenon was found to be associated with sera boosted with exogenous alkaline phosphatase and to be owing mainly to inadequate provision of buffer in some automated methods. It is suggested that a modification to the SMA procedure may lessen the problem, but the constraints of the system necessitate a compromise. There was better precision after the modification had been introduced. Awareness of this phenomenon is of paramount importance if commerical sera are to be used in any way in the calibration of automated systems for alkaline phosphatase assay.", "contents": "Anomalous behaviour of control sera in automated versions of the Kind and King alkaline phosphatase method. Differences in alkaline phosphatase activity of some commerical control sera were observed when comparing manual with AutoAnalyzer versions of the Kind and King procedure. This phenomenon was found to be associated with sera boosted with exogenous alkaline phosphatase and to be owing mainly to inadequate provision of buffer in some automated methods. It is suggested that a modification to the SMA procedure may lessen the problem, but the constraints of the system necessitate a compromise. There was better precision after the modification had been introduced. Awareness of this phenomenon is of paramount importance if commerical sera are to be used in any way in the calibration of automated systems for alkaline phosphatase assay."}
{"id": "PMID:28069", "title": "A comparison of two methods of quality control of pH, Pco2, and Po2 measurements.", "content": "pH, Pco2, and Po2 measurements have been made over a three-week period on General Diagnostics Blood GAS Control Ampoules and on a tonometered buffer system. The latter seems adequate as a precision and accuracy control of pH, Pco2, and Po2 measurements in a single solution. The former seems adequate as a precision control of these measurements, but, on the particular batch provided, mean values need to be determined within the customer's laboratory.", "contents": "A comparison of two methods of quality control of pH, Pco2, and Po2 measurements. pH, Pco2, and Po2 measurements have been made over a three-week period on General Diagnostics Blood GAS Control Ampoules and on a tonometered buffer system. The latter seems adequate as a precision and accuracy control of pH, Pco2, and Po2 measurements in a single solution. The former seems adequate as a precision control of these measurements, but, on the particular batch provided, mean values need to be determined within the customer's laboratory."}
{"id": "PMID:28070", "title": "A comparison between metoprolol and pindolol in the treatment of essential hypertension.", "content": "The antihypertensive effects on metoprolol and pindolol were compared in 50 patients with essential hypertension belonging to WHO stage 1 or 2. After four weeks of placebo treatment the patients were randomly allocated to treatment with metoprolol or pindolol. During the initial dose-titration period of six weeks the dose was individually adjusted, aiming at a diastolic blood pressure in the seated position less than 95 mm Hg. The maximum possible dosage for metoprolol was 50, 100 and 150 mg b.i.d. and for pindolol 5, 10 and 15 mg b.i.d. Thereafter followed a fixed-dose period of 20 weeks. Six patients did not complete the study. At the end of the study satisfactory blood pressure control, defined as a diastolic blood pressure in the seated position less than 95 mm Hg, was achieved in 15 of the 20 patients (75%) in the metroprolol group and in 13 out of 24 patients (54%) in the pindolol group. The average reduction in diastolic blood pressure was more pronounced with metoprolol than with pindolol, while no difference was found between the two beta-blockers with regard to the reduction of the systolic blood pressure. Generally, metoprolol and pindolol were both well tolerated by the patients.", "contents": "A comparison between metoprolol and pindolol in the treatment of essential hypertension. The antihypertensive effects on metoprolol and pindolol were compared in 50 patients with essential hypertension belonging to WHO stage 1 or 2. After four weeks of placebo treatment the patients were randomly allocated to treatment with metoprolol or pindolol. During the initial dose-titration period of six weeks the dose was individually adjusted, aiming at a diastolic blood pressure in the seated position less than 95 mm Hg. The maximum possible dosage for metoprolol was 50, 100 and 150 mg b.i.d. and for pindolol 5, 10 and 15 mg b.i.d. Thereafter followed a fixed-dose period of 20 weeks. Six patients did not complete the study. At the end of the study satisfactory blood pressure control, defined as a diastolic blood pressure in the seated position less than 95 mm Hg, was achieved in 15 of the 20 patients (75%) in the metroprolol group and in 13 out of 24 patients (54%) in the pindolol group. The average reduction in diastolic blood pressure was more pronounced with metoprolol than with pindolol, while no difference was found between the two beta-blockers with regard to the reduction of the systolic blood pressure. Generally, metoprolol and pindolol were both well tolerated by the patients."}
{"id": "PMID:28071", "title": "Penbutolol, a new non-selective beta-adrenergic blocking compound in the treatment of hypertension. A comparision with propranolol.", "content": "The antihypertensive effect of a new non-selective beta-adrenergic blocking compound, penbutolol (40 mg b.i.d.), was compared with propranolol (160 mg b.i.d.) in a series of 20 hypertensive patients using a double-blind cross-over scheme. Both compounds reduced both the supine and the standing blood pressure significantly. The magnitude of the responses did not differ significantly and both compounds evoked a commensurate decrease in heart rate. No significant side-effects were noted and a series of laboratory tests did not disclose any biochemical changes.", "contents": "Penbutolol, a new non-selective beta-adrenergic blocking compound in the treatment of hypertension. A comparision with propranolol. The antihypertensive effect of a new non-selective beta-adrenergic blocking compound, penbutolol (40 mg b.i.d.), was compared with propranolol (160 mg b.i.d.) in a series of 20 hypertensive patients using a double-blind cross-over scheme. Both compounds reduced both the supine and the standing blood pressure significantly. The magnitude of the responses did not differ significantly and both compounds evoked a commensurate decrease in heart rate. No significant side-effects were noted and a series of laboratory tests did not disclose any biochemical changes."}
{"id": "PMID:28072", "title": "Response of left ventricular myocardial perfusion and cavity size to beta-blockade by acebutolol.", "content": "The effect of beta-blockade by acebutolol on global and regional myocardial perfusion (133Xenon wash-out) was studied in 10 patients with coronary artery disease. Another group of 10 similar patients was used to study the effect of acebutolol on left ventricular cavity size (metal markers--spot film camera). Global perfusion responses roughly paralleled the changes in rate-pressure variable which decreased in 8 patients and increased in 2 who had spontaneous angina pectoris. Regional perfusion decreased more in areas distal to less than 75% stenoses than in those distal to less than 75% stenoses (29 vs 12%; p = 0.10 less than 0.20). Left ventricular asynergy did not modify the response, nor did the presence or absence of collateral vessels. No evidence was found to support the thesis that beta-blockade may evoke a redistribution in perfusion which favours the potentially ischaemic areas of myocardium. Left ventricular cavity size remained unchanged after acebutolol, a cardioselective beta-blocking compound with some degree of agonist activity.", "contents": "Response of left ventricular myocardial perfusion and cavity size to beta-blockade by acebutolol. The effect of beta-blockade by acebutolol on global and regional myocardial perfusion (133Xenon wash-out) was studied in 10 patients with coronary artery disease. Another group of 10 similar patients was used to study the effect of acebutolol on left ventricular cavity size (metal markers--spot film camera). Global perfusion responses roughly paralleled the changes in rate-pressure variable which decreased in 8 patients and increased in 2 who had spontaneous angina pectoris. Regional perfusion decreased more in areas distal to less than 75% stenoses than in those distal to less than 75% stenoses (29 vs 12%; p = 0.10 less than 0.20). Left ventricular asynergy did not modify the response, nor did the presence or absence of collateral vessels. No evidence was found to support the thesis that beta-blockade may evoke a redistribution in perfusion which favours the potentially ischaemic areas of myocardium. Left ventricular cavity size remained unchanged after acebutolol, a cardioselective beta-blocking compound with some degree of agonist activity."}
{"id": "PMID:28073", "title": "Further characterization of bound measles-specific IgG eluted from SSPE brains.", "content": "Tissue residues from 3 SSPE brains extracted at neutral pH were thoroughly washed with phosphate-buffered saline and further extracted at acidic pH. The low-pH extracts had significant measles antibody titers, and their measles-specific IgG content ranged from 40 to 60% of total IgG. Agarose-gel electrophoretic analysis of the extracts showed oligoclonal IgG bands, most of which disappeared after suitable absorption with measles virus, demonstrating the presence of restricted measles antibody population. Ouchterlony analysis showed a reaction of identity between bound IgG and IgG extracted at neutral pH. Thus IgG extracted at low and neutral pHs is remarkably similar.", "contents": "Further characterization of bound measles-specific IgG eluted from SSPE brains. Tissue residues from 3 SSPE brains extracted at neutral pH were thoroughly washed with phosphate-buffered saline and further extracted at acidic pH. The low-pH extracts had significant measles antibody titers, and their measles-specific IgG content ranged from 40 to 60% of total IgG. Agarose-gel electrophoretic analysis of the extracts showed oligoclonal IgG bands, most of which disappeared after suitable absorption with measles virus, demonstrating the presence of restricted measles antibody population. Ouchterlony analysis showed a reaction of identity between bound IgG and IgG extracted at neutral pH. Thus IgG extracted at low and neutral pHs is remarkably similar."}
{"id": "PMID:28076", "title": "Extracellular accumulation of a new amino acid, O-2-hydroxypropylhomoserine, from 1,2-propanediol by flavobacterium rigense.", "content": "During an investigation of microorganisms utilizing petrochemicals, a strain identified as Flavobacterium rigense was found to accumulate a new amino acid in a medium containing 1,2-propanediol as the sole carbon source. Cultural conditions for the accumulation of the product were investigated, and as a result, the yield was increased to 2.8 mg/ml after a 5-day incubation in a medium containing 8% 1,2-propanediol. The pure amino acid was isolated, and its structure was investigated. Elemental analysis and infrared, nuclear magnetic resonance, and mass spectral analyses indicated that the amino acids is O-2-hydroxypropylhomoserine.", "contents": "Extracellular accumulation of a new amino acid, O-2-hydroxypropylhomoserine, from 1,2-propanediol by flavobacterium rigense. During an investigation of microorganisms utilizing petrochemicals, a strain identified as Flavobacterium rigense was found to accumulate a new amino acid in a medium containing 1,2-propanediol as the sole carbon source. Cultural conditions for the accumulation of the product were investigated, and as a result, the yield was increased to 2.8 mg/ml after a 5-day incubation in a medium containing 8% 1,2-propanediol. The pure amino acid was isolated, and its structure was investigated. Elemental analysis and infrared, nuclear magnetic resonance, and mass spectral analyses indicated that the amino acids is O-2-hydroxypropylhomoserine."}
{"id": "PMID:28077", "title": "Viral aggregation: quantitation and kinetics of the aggregation of poliovirus and reovirus.", "content": "The aggregation of poliovirus and reovirus was followed in buffers at various pH values by means of a single particle analysis (SPA) test. The SPA test used here was modified from the original test reported earlier to prevent disaggregation of virus clumps from invalidating the results. The modified SPA test demonstrated that the efficiency of aggregation, which is a measure of the percentage of collisions which are effective in producing an aggregate, may vary widely depending on the conditions in which the virus is placed. The modified SPA test was also used to demonstrate that the kinetic features of viral aggregation follow the classical laws of colloid particle aggregation, which in turn are solely dependent upon diffusion of the particles as caused by brownian motion.", "contents": "Viral aggregation: quantitation and kinetics of the aggregation of poliovirus and reovirus. The aggregation of poliovirus and reovirus was followed in buffers at various pH values by means of a single particle analysis (SPA) test. The SPA test used here was modified from the original test reported earlier to prevent disaggregation of virus clumps from invalidating the results. The modified SPA test demonstrated that the efficiency of aggregation, which is a measure of the percentage of collisions which are effective in producing an aggregate, may vary widely depending on the conditions in which the virus is placed. The modified SPA test was also used to demonstrate that the kinetic features of viral aggregation follow the classical laws of colloid particle aggregation, which in turn are solely dependent upon diffusion of the particles as caused by brownian motion."}
{"id": "PMID:28078", "title": "Viral aggregation: effects of salts on the aggregation of poliovirus and reovirus at low pH.", "content": "As a first step toward the understanding of virus particle interactions in water, we have used the modified single particle analysis test to follow the aggregation of poliovirus and reovirus as induced by low pH in suspensions containing varying amounts of dissolved salts. Salts composed of mono-, di-, and trivalent cations and mono- and divalent anions were tested for their ability to reduce or increase the aggregation of these viruses in relation to that obtained by low pH alone. Mono- and divalent cations in concentrations covering those in natural waters were generally found to cause a decrease in aggregation, with the divalent cations having a much greater effectiveness than the monovalent cations. Trivalent ions (Al3+), in micromolar concentrations, were found to cause aggregation over that at low pH alone. Anions, whether monovalent or divalent, had little ability to produce inhibition of viral aggregation, and thus the overall effects were due almost exclusively to the cation. This was true regardless of whether the overall charge on the virus particle was positive or negative, as determined by the relation between the isoelectric point and the pH at which the tests were carried out. Thus, whereas virus particles conform to classical colloid theory in many respects, there are specific exceptions which must be taken into account in the design of any experiment in which viral aggregation is a factor.", "contents": "Viral aggregation: effects of salts on the aggregation of poliovirus and reovirus at low pH. As a first step toward the understanding of virus particle interactions in water, we have used the modified single particle analysis test to follow the aggregation of poliovirus and reovirus as induced by low pH in suspensions containing varying amounts of dissolved salts. Salts composed of mono-, di-, and trivalent cations and mono- and divalent anions were tested for their ability to reduce or increase the aggregation of these viruses in relation to that obtained by low pH alone. Mono- and divalent cations in concentrations covering those in natural waters were generally found to cause a decrease in aggregation, with the divalent cations having a much greater effectiveness than the monovalent cations. Trivalent ions (Al3+), in micromolar concentrations, were found to cause aggregation over that at low pH alone. Anions, whether monovalent or divalent, had little ability to produce inhibition of viral aggregation, and thus the overall effects were due almost exclusively to the cation. This was true regardless of whether the overall charge on the virus particle was positive or negative, as determined by the relation between the isoelectric point and the pH at which the tests were carried out. Thus, whereas virus particles conform to classical colloid theory in many respects, there are specific exceptions which must be taken into account in the design of any experiment in which viral aggregation is a factor."}
{"id": "PMID:28079", "title": "Simple method for the isolation of astaxanthin from the basidiomycetous yeast Phaffia rhodozyma.", "content": "A method is described for the quantitative and, possibly, large-scale extraction of astaxanthin from the yeast Phaffia rhodozyma. The method utilizes extracellular enzymes produced by the bacterium Bacillus circulans WL-12, which partially digests the yeast cell wall and renders the carotenoid pigments extractable by acetone or ethanol. Complete recovery of astaxanthin from heat-killed P. rhodozyma cells was obtained after growing B. circulans WL-12 on these yeast cells for 26 h and then extracting the yeast-bacterium mixture with acetone. A bacteria-free lytic system, which gave quantitative extraction of astaxanthin from P. rhodozyma, was obtained by concentrating the culture broth from the growth of B. circulans WL-12 on P. rhodozyma cells. Hydrolytic enzyme activities detected in this concentrate included beta-(1 leads to 3)-glucanase, beta-(1 leads to 6)-glucanase, alpha-(1 leads to 3)-glucanase, xylanase, and chitinase. The lytic system was found to work most efficiently at pH 6.5 and with low concentrations of yeast.", "contents": "Simple method for the isolation of astaxanthin from the basidiomycetous yeast Phaffia rhodozyma. A method is described for the quantitative and, possibly, large-scale extraction of astaxanthin from the yeast Phaffia rhodozyma. The method utilizes extracellular enzymes produced by the bacterium Bacillus circulans WL-12, which partially digests the yeast cell wall and renders the carotenoid pigments extractable by acetone or ethanol. Complete recovery of astaxanthin from heat-killed P. rhodozyma cells was obtained after growing B. circulans WL-12 on these yeast cells for 26 h and then extracting the yeast-bacterium mixture with acetone. A bacteria-free lytic system, which gave quantitative extraction of astaxanthin from P. rhodozyma, was obtained by concentrating the culture broth from the growth of B. circulans WL-12 on P. rhodozyma cells. Hydrolytic enzyme activities detected in this concentrate included beta-(1 leads to 3)-glucanase, beta-(1 leads to 6)-glucanase, alpha-(1 leads to 3)-glucanase, xylanase, and chitinase. The lytic system was found to work most efficiently at pH 6.5 and with low concentrations of yeast."}
{"id": "PMID:28080", "title": "Sulfide oxidation by spheroplasts of Thiobacillus ferrooxidans.", "content": "Thiobacillus ferrooxidans is an acidophilic organism important to metal leaching of low-grade ores. The aforementioned importance is related to the ability of the bacterium to oxidize reduced iron and sulfur, principally found in nature as pyrite (FeS2). The present study dealt with sulfide oxidation at low pH values and the involvement of the cell envelope in the process of the inorganic oxidations. Sulfide oxidation was noted in spheroplasts of T. ferrooxidans prepared by enzymatic and chemical treatments and partially purified by differential centrifugation. No enzyme activities were noted in membrane fractions containing enrichments of lipopolysaccharide symbolic of outer membrane material or in membrane vesicles containing (or associated with) higher levels of proteins. Results to date indicate that in an acid milieu the envelope structure containing both the outer membrane and the intact inner cytoplasmic membrane is required for sulfide oxidation.", "contents": "Sulfide oxidation by spheroplasts of Thiobacillus ferrooxidans. Thiobacillus ferrooxidans is an acidophilic organism important to metal leaching of low-grade ores. The aforementioned importance is related to the ability of the bacterium to oxidize reduced iron and sulfur, principally found in nature as pyrite (FeS2). The present study dealt with sulfide oxidation at low pH values and the involvement of the cell envelope in the process of the inorganic oxidations. Sulfide oxidation was noted in spheroplasts of T. ferrooxidans prepared by enzymatic and chemical treatments and partially purified by differential centrifugation. No enzyme activities were noted in membrane fractions containing enrichments of lipopolysaccharide symbolic of outer membrane material or in membrane vesicles containing (or associated with) higher levels of proteins. Results to date indicate that in an acid milieu the envelope structure containing both the outer membrane and the intact inner cytoplasmic membrane is required for sulfide oxidation."}
{"id": "PMID:28081", "title": "Induction of colonial growth and replica plating of the white rot basidiomycete Phanaerochaete chrysosporium.", "content": "A medium containing L-sorbose and sodium deoxycholate was devised which induces colonial growth of Phanaerochaete chrysosporium in the presence of a variety of supplements. The restricted size and heavy conidial production of the colonies permits high plating densities and the use of a replica-plating technique for copying the pattern of colony growth.", "contents": "Induction of colonial growth and replica plating of the white rot basidiomycete Phanaerochaete chrysosporium. A medium containing L-sorbose and sodium deoxycholate was devised which induces colonial growth of Phanaerochaete chrysosporium in the presence of a variety of supplements. The restricted size and heavy conidial production of the colonies permits high plating densities and the use of a replica-plating technique for copying the pattern of colony growth."}
{"id": "PMID:28094", "title": "Preliminary data on antiserotonin effects of oxatomide, a novel anti-allergic compound.", "content": "Oxatomide or R 35443, 1-(3-[4-(diphenylmethyl)-1-piperazinyl]propyl)-1,3-dihydro--2H-benzimidazol-2-one, a compound with potent antihistaminic and anti-anaphylactic activities, shows specific antiserotonin effects on isolated caudal arteries of the rat. In vivo it is a powerful antagonist of bronchospasm induced by serotonin and by histamine; it has no anticholinergic effects and does not affect blood pressure in spontaneously hypertensive rats. These antiserotonin properties of oxatomide may contribute significantly to its anti-allergic activity.", "contents": "Preliminary data on antiserotonin effects of oxatomide, a novel anti-allergic compound. Oxatomide or R 35443, 1-(3-[4-(diphenylmethyl)-1-piperazinyl]propyl)-1,3-dihydro--2H-benzimidazol-2-one, a compound with potent antihistaminic and anti-anaphylactic activities, shows specific antiserotonin effects on isolated caudal arteries of the rat. In vivo it is a powerful antagonist of bronchospasm induced by serotonin and by histamine; it has no anticholinergic effects and does not affect blood pressure in spontaneously hypertensive rats. These antiserotonin properties of oxatomide may contribute significantly to its anti-allergic activity."}
{"id": "PMID:28095", "title": "Discriminable effects of antihistamine drugs.", "content": "Rats were trained to discriminate drug vs. no-drug in a shock-escape T-maze task; a right turn was required when rats were drugged and a left turn when undrugged. The three antihistamine drugs pyrilamine, dimenhydrinate (Dramamine) and diphenhydramine (Benadryl) were discriminated after an average of 20 training sessions indicating that their effects were only moderately discriminable. After criterion performance was achieved under the training conditions, substitution tests were conducted during which rats received a novel drug and were then run in the maze with both goals accessible. Rats trained with antihistamine drugs made drug choices during tests with other antihistamines. Rats trained with other types of drugs made no-drug choices during tests with antihistamines. The results suggest that the antihistamines share a discriminable effect which is relatively unique to that class of drugs.", "contents": "Discriminable effects of antihistamine drugs. Rats were trained to discriminate drug vs. no-drug in a shock-escape T-maze task; a right turn was required when rats were drugged and a left turn when undrugged. The three antihistamine drugs pyrilamine, dimenhydrinate (Dramamine) and diphenhydramine (Benadryl) were discriminated after an average of 20 training sessions indicating that their effects were only moderately discriminable. After criterion performance was achieved under the training conditions, substitution tests were conducted during which rats received a novel drug and were then run in the maze with both goals accessible. Rats trained with antihistamine drugs made drug choices during tests with other antihistamines. Rats trained with other types of drugs made no-drug choices during tests with antihistamines. The results suggest that the antihistamines share a discriminable effect which is relatively unique to that class of drugs."}
{"id": "PMID:28096", "title": "Clobazam. A 1.5 benzodiazepine derivative: effects upon human psychomotor performance under different levels of task reinforcement.", "content": "Two dose levels of clobazam, a benzodiazepine derivative, were compared to placebo for their effects upon psychomotor performance in an acute dose daytime study with normals. An acute dose of 10 mg clobazam significantly reduced response latencies in the low reinforcement condition of a psychomotor performance task but not in the high reinforcement condition. However 20 mg clobazam did not produce any significant changes in performance under either low or high reinforcement. Response speed changes generally correlated positively with trait anziety and neuroticism scores at both doses of clobazam.", "contents": "Clobazam. A 1.5 benzodiazepine derivative: effects upon human psychomotor performance under different levels of task reinforcement. Two dose levels of clobazam, a benzodiazepine derivative, were compared to placebo for their effects upon psychomotor performance in an acute dose daytime study with normals. An acute dose of 10 mg clobazam significantly reduced response latencies in the low reinforcement condition of a psychomotor performance task but not in the high reinforcement condition. However 20 mg clobazam did not produce any significant changes in performance under either low or high reinforcement. Response speed changes generally correlated positively with trait anziety and neuroticism scores at both doses of clobazam."}
{"id": "PMID:28097", "title": "Studies on the inhibition by beta adrenergic receptor agonists of cyclic AMP phosphodiesterase activity of rat heart.", "content": "Isoproterenol (10(-5) and 10(-4)M) inhibited a low affinity but not a high affinity form of rat heart cyclic AMP phosphodiesterase. The concentrations of isoproterenol required to produce inhibition of the isolated enzyme were 10,000 to 100,000 fold larger than those required to produce a positive chronotropic response in the isolated atria. Another beta adrenergic receptor agonist, soterenol, had no effect on any of the isolated forms of the enzyme. Theophylline produced inhibition of low and high affinity forms of phosphodiesterase at the same concentrations required to produce a positive chronotropic response in the isolated atria. Results from two experimental models failed to reveal any circumstances under which a contribution to the positive chronotropic response could result from isoproterenol-induced inhibition of cyclic AMP phosphodiesterase.", "contents": "Studies on the inhibition by beta adrenergic receptor agonists of cyclic AMP phosphodiesterase activity of rat heart. Isoproterenol (10(-5) and 10(-4)M) inhibited a low affinity but not a high affinity form of rat heart cyclic AMP phosphodiesterase. The concentrations of isoproterenol required to produce inhibition of the isolated enzyme were 10,000 to 100,000 fold larger than those required to produce a positive chronotropic response in the isolated atria. Another beta adrenergic receptor agonist, soterenol, had no effect on any of the isolated forms of the enzyme. Theophylline produced inhibition of low and high affinity forms of phosphodiesterase at the same concentrations required to produce a positive chronotropic response in the isolated atria. Results from two experimental models failed to reveal any circumstances under which a contribution to the positive chronotropic response could result from isoproterenol-induced inhibition of cyclic AMP phosphodiesterase."}
{"id": "PMID:28098", "title": "The role of vanadium in green plants. IV. Influence on the formation of delta-aminolevulinic acid in Chlorella.", "content": "In a series of experiments, it is demonstrated that the trace element vanadium (4.10(-7) g-at/1 as NH4VO3) has a considerable positive influence on the synthesis of delta-aminolevulinic acid(delta-ALA) in the autotrophically growing green alga Chlorella pyrenoidosa, the effect being visible by an enhanced output of the amino acid into the culture medium in presence of levulinic acid (LA). The level of intracellularly accumulated delta-ALA, however, is not changed in presence of the metal. The V-effect on exogenous found delta-ALA is suppressed, when LA is added to the nutrient medium at low pH (pH5), although V-uptake into the algal cells is not disturbed by LA. As demonstrated in culture media with various nitrogen sources (urea, partially hydrolized urea, ammonium salts), the development of the pH during the cultivation time is important for the presentation of the V-effect on delta-ALA. It is suggested that vanadium acts as a catalyst in the conversion of 4,5-dioxovaleric acid to delta-ALA by transamination.", "contents": "The role of vanadium in green plants. IV. Influence on the formation of delta-aminolevulinic acid in Chlorella. In a series of experiments, it is demonstrated that the trace element vanadium (4.10(-7) g-at/1 as NH4VO3) has a considerable positive influence on the synthesis of delta-aminolevulinic acid(delta-ALA) in the autotrophically growing green alga Chlorella pyrenoidosa, the effect being visible by an enhanced output of the amino acid into the culture medium in presence of levulinic acid (LA). The level of intracellularly accumulated delta-ALA, however, is not changed in presence of the metal. The V-effect on exogenous found delta-ALA is suppressed, when LA is added to the nutrient medium at low pH (pH5), although V-uptake into the algal cells is not disturbed by LA. As demonstrated in culture media with various nitrogen sources (urea, partially hydrolized urea, ammonium salts), the development of the pH during the cultivation time is important for the presentation of the V-effect on delta-ALA. It is suggested that vanadium acts as a catalyst in the conversion of 4,5-dioxovaleric acid to delta-ALA by transamination."}
{"id": "PMID:28100", "title": "[Endocrine data in cryptorchism].", "content": "Endocrine evaluation with LH-RH (0.1 mg/m2) and chorionic gonadotrophin (HCG 3 X 1,500 I.U.) in 154 cryptorchid boys aged 1 month to 15 years showed a decrease of LH pituitary secretion and Leydig-cells response to HCG in prepubertal and early pubertal patients. These deficiencies were positively correlated. Partial and at least transient descent of cryptorchid testis or testes has been obtained in 87 of 265 patients treated with HCG (3 to 9 X 1,500 I.U.). Plasma testosterone after HCG 3 X 1,500 I.U. was less increased in patients whose cryptorchid testis or testes descended after 9 X 1,500 I.U. than in those whose testes remained undescended. These data suggest that a partial, early and transient deficiency of pituitary LH secretion may be responsible for testicular maldescent in part of cryptorchid boys.", "contents": "[Endocrine data in cryptorchism]. Endocrine evaluation with LH-RH (0.1 mg/m2) and chorionic gonadotrophin (HCG 3 X 1,500 I.U.) in 154 cryptorchid boys aged 1 month to 15 years showed a decrease of LH pituitary secretion and Leydig-cells response to HCG in prepubertal and early pubertal patients. These deficiencies were positively correlated. Partial and at least transient descent of cryptorchid testis or testes has been obtained in 87 of 265 patients treated with HCG (3 to 9 X 1,500 I.U.). Plasma testosterone after HCG 3 X 1,500 I.U. was less increased in patients whose cryptorchid testis or testes descended after 9 X 1,500 I.U. than in those whose testes remained undescended. These data suggest that a partial, early and transient deficiency of pituitary LH secretion may be responsible for testicular maldescent in part of cryptorchid boys."}
{"id": "PMID:28102", "title": "Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study.", "content": "The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance.", "contents": "Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study. The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance."}
{"id": "PMID:28103", "title": "Vestibular responses in schizophrenia.", "content": "In a study of vestibular responses to caloric stimulation that controlled opportunity for fixation and state of alertness, we evaluated previous findings of diminished nystagmus in schizophrenia. We failed to replicate earlier reports in these respects: (1) None of the psychotic patient groups, when compared with normal controls, showed lower response intensity, latency, or culmination time of the nystagmic response. (2) The schizophrenic groups did not manifest a prevalence of clinically significant asymmetry. We did, however, observe that chronic deteriorated schizophrenics and recent schizophrenics have significantly greater dysrhythmic responses. This diminished orderliness of nystagmus may explain previous reports of absent or diminished nystagmus in the schizophrenics. The results are not compatible with peripheral vestibular disease in schizophrenia, but they may reflect state-related phenomena consistent with disturbances in alertness, which are not necessarily voluntary or motivational in origin.", "contents": "Vestibular responses in schizophrenia. In a study of vestibular responses to caloric stimulation that controlled opportunity for fixation and state of alertness, we evaluated previous findings of diminished nystagmus in schizophrenia. We failed to replicate earlier reports in these respects: (1) None of the psychotic patient groups, when compared with normal controls, showed lower response intensity, latency, or culmination time of the nystagmic response. (2) The schizophrenic groups did not manifest a prevalence of clinically significant asymmetry. We did, however, observe that chronic deteriorated schizophrenics and recent schizophrenics have significantly greater dysrhythmic responses. This diminished orderliness of nystagmus may explain previous reports of absent or diminished nystagmus in the schizophrenics. The results are not compatible with peripheral vestibular disease in schizophrenia, but they may reflect state-related phenomena consistent with disturbances in alertness, which are not necessarily voluntary or motivational in origin."}
{"id": "PMID:28104", "title": "[Proteolytic activities in mature human placenta. II. Neutral peptidases and PZ-peptidase (author's transl)].", "content": "Continuing our contributions on proteases of human placenta we enriched some unidentified neutral peptidases by chromatographying freeze dried placenta extracts on CM-Sephadex, followed by preparative isoelectric focusing and chromatography on Ultrogel. By this procedure two Acetyl-aminoacyl-p-nitranilidases, three Ala-Ala-p-nitranilidases, one Benzyloxycarbonyl-Ala-Ala-p-nitranilidase, one Carbobenzoxy-Gly-Pro-Arg-p-nitranilidase and one PZ-peptidase could be characterized in greater detail. Here molecular weights, isoelectric points and pH-optima of these enzymes are reported.", "contents": "[Proteolytic activities in mature human placenta. II. Neutral peptidases and PZ-peptidase (author's transl)]. Continuing our contributions on proteases of human placenta we enriched some unidentified neutral peptidases by chromatographying freeze dried placenta extracts on CM-Sephadex, followed by preparative isoelectric focusing and chromatography on Ultrogel. By this procedure two Acetyl-aminoacyl-p-nitranilidases, three Ala-Ala-p-nitranilidases, one Benzyloxycarbonyl-Ala-Ala-p-nitranilidase, one Carbobenzoxy-Gly-Pro-Arg-p-nitranilidase and one PZ-peptidase could be characterized in greater detail. Here molecular weights, isoelectric points and pH-optima of these enzymes are reported."}
{"id": "PMID:28105", "title": "Concept of paraneurons.", "content": "Paraneurons are those cells which have not been designated as neurons but are recognized as closely related to neurons on the basis of their fine structure (possession of neurosecretion-like and synaptic vesicle-like granules/vacuoles), metabolism (production of neurosecretion- and neurotransmitter-like substances) and origin (evidenced or proposed neuroectodermal). Some paraneurons are mainly endocrine in function, while others are sensory. Some should be called interneurons. There are graduations between these types of paraneurons; also a definite boundary between neurons and paraneurons can not be determined. Different types of paraneurons (together with some related neurons) are shown in Figure 1. Comments and discussions were given on the neuron-like characteristics of the individual paraneurons.", "contents": "Concept of paraneurons. Paraneurons are those cells which have not been designated as neurons but are recognized as closely related to neurons on the basis of their fine structure (possession of neurosecretion-like and synaptic vesicle-like granules/vacuoles), metabolism (production of neurosecretion- and neurotransmitter-like substances) and origin (evidenced or proposed neuroectodermal). Some paraneurons are mainly endocrine in function, while others are sensory. Some should be called interneurons. There are graduations between these types of paraneurons; also a definite boundary between neurons and paraneurons can not be determined. Different types of paraneurons (together with some related neurons) are shown in Figure 1. Comments and discussions were given on the neuron-like characteristics of the individual paraneurons."}
{"id": "PMID:28107", "title": "Neuro-epithelial bodies in the lung of the rat and the mouse.", "content": "Histochemical and ultrastructural examinations were performed on neuroepithelial bodies (N. E. B.) in the lung of the mouse and rat. The N. E. B. were identified as specialized groups of pale, columnar cells. They were located throughout the intrapulmonary airway. These cells displayed some special cytochemical properties also seen in the APUD (Amine Precursors Uptake and Decarboxylation) endocrine system, such as cytoplasmic argyrophilia and the capability of selective uptake of amine precursors. Ultrastructrally the N. E. B. were composed of a kind of granulated cell which had concentrations of specific cored vesicles in the basal cytoplasm. It seemed likely that the cells released the contents of the cored vesicles into the extracellular space by exocytosis. These cells made extensive and intimate contact with the mitochondria-rich nerve terminals which occurred mainly at the level of the supranuclear portions of the granulated cells. In this contact area, the membrane of the nerve terminals were apposed to that of the granulated cells with a consistent gap of about 20 nm. Among these membrane appositions, some membrane thickenings were observed in which cored vesicles were closely associated in the granulated cell cytoplasm. From these observations, it was conceived that the lung N. E. B. function both as receptor and endocrine organs and that their specific cored vesicles may have an intimate correlation with these dual functions.", "contents": "Neuro-epithelial bodies in the lung of the rat and the mouse. Histochemical and ultrastructural examinations were performed on neuroepithelial bodies (N. E. B.) in the lung of the mouse and rat. The N. E. B. were identified as specialized groups of pale, columnar cells. They were located throughout the intrapulmonary airway. These cells displayed some special cytochemical properties also seen in the APUD (Amine Precursors Uptake and Decarboxylation) endocrine system, such as cytoplasmic argyrophilia and the capability of selective uptake of amine precursors. Ultrastructrally the N. E. B. were composed of a kind of granulated cell which had concentrations of specific cored vesicles in the basal cytoplasm. It seemed likely that the cells released the contents of the cored vesicles into the extracellular space by exocytosis. These cells made extensive and intimate contact with the mitochondria-rich nerve terminals which occurred mainly at the level of the supranuclear portions of the granulated cells. In this contact area, the membrane of the nerve terminals were apposed to that of the granulated cells with a consistent gap of about 20 nm. Among these membrane appositions, some membrane thickenings were observed in which cored vesicles were closely associated in the granulated cell cytoplasm. From these observations, it was conceived that the lung N. E. B. function both as receptor and endocrine organs and that their specific cored vesicles may have an intimate correlation with these dual functions."}
{"id": "PMID:28108", "title": "Cimetidine, carbenoxolone sodium, and antacids for the prevention of experimental stress ulcers.", "content": "Cimetidine, an H2-receptor, antagonist, and carbenoxolone sodium, a drug used to stimulate gastric mucus synthesis and increase the life span of gastric epithelial cells, were studied to determine their possible prophylactic effect on the formation of stress ulcers, gastric transmucosal potential difference and  gastric pH in rats, using a restraint stress model. The number of ulcers substantially decreased in the rat groups receiving either cimetidine or carbenoxolone pretreatment for two or more days before stress. When the drugs were used in combination, there was an additive effect, since there was a significant decrease in ulcer formation even after half a day of pretreatment. When antacids were used, there was also decreased ulcer formation with half a day of pretreatment. Gastric pH was significantly increased from control levels in all the groups treated with antacid, cimetidine and carbenoxolone. Both cimetidine and carbenoxolone, either alone or in combination, prevented the decrease in potential difference that was produced in the untreated stressed rats. This study suggests that either cimetidine or carbenoxolone, and particularly their combination, may be a useful prophylactic regimen for the prevention of stress ulceration in patients subjected to severe stress.", "contents": "Cimetidine, carbenoxolone sodium, and antacids for the prevention of experimental stress ulcers. Cimetidine, an H2-receptor, antagonist, and carbenoxolone sodium, a drug used to stimulate gastric mucus synthesis and increase the life span of gastric epithelial cells, were studied to determine their possible prophylactic effect on the formation of stress ulcers, gastric transmucosal potential difference and  gastric pH in rats, using a restraint stress model. The number of ulcers substantially decreased in the rat groups receiving either cimetidine or carbenoxolone pretreatment for two or more days before stress. When the drugs were used in combination, there was an additive effect, since there was a significant decrease in ulcer formation even after half a day of pretreatment. When antacids were used, there was also decreased ulcer formation with half a day of pretreatment. Gastric pH was significantly increased from control levels in all the groups treated with antacid, cimetidine and carbenoxolone. Both cimetidine and carbenoxolone, either alone or in combination, prevented the decrease in potential difference that was produced in the untreated stressed rats. This study suggests that either cimetidine or carbenoxolone, and particularly their combination, may be a useful prophylactic regimen for the prevention of stress ulceration in patients subjected to severe stress."}
{"id": "PMID:28109", "title": "[The effect of pelleting cereal straw with NaOH-addition on rumen fermentation in cows].", "content": "Experiments with rumen-fistulated dairy cows were performed to study the effect of NaOH-addition to cereal pellets. Compared to straw-concentrate rations in which the straw pellets were free of NaOH, cereal straw pellets containing 2.4 kg NaOH per 100 kg straw caused the rumenal pH to go up from 6.21 to 6.47, the cellulotlytic activity to rise by some 20%, and the passage turnover rate of dry matter to increase from 0,039 to 0,056. The concentrations of volatile fatty acids and the fermentation patterns were not influenced by the NaOH-content of the pellets. It is concluded that NaOH-addition during straw pelleting has a favourable effect on digestion in the bovine rumen.", "contents": "[The effect of pelleting cereal straw with NaOH-addition on rumen fermentation in cows]. Experiments with rumen-fistulated dairy cows were performed to study the effect of NaOH-addition to cereal pellets. Compared to straw-concentrate rations in which the straw pellets were free of NaOH, cereal straw pellets containing 2.4 kg NaOH per 100 kg straw caused the rumenal pH to go up from 6.21 to 6.47, the cellulotlytic activity to rise by some 20%, and the passage turnover rate of dry matter to increase from 0,039 to 0,056. The concentrations of volatile fatty acids and the fermentation patterns were not influenced by the NaOH-content of the pellets. It is concluded that NaOH-addition during straw pelleting has a favourable effect on digestion in the bovine rumen."}
{"id": "PMID:28110", "title": "[On the toxicology of carbromal. III. Role of active metabolites in humans acutely poisoned with carbromal-containing sedatives (author's transl)].", "content": "Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumoles/l, for bromoethylbutyramide up to 20 mumoles/l and for ethylbutyrylurea 2--3 mumoles/l. In patients acutely poisoned by carbromal-containing sedatives serum concentrations measured were in the range of 200 mumoles/l carbromal, 350 mumoles/l bromoethylbutyramide and 50 mumoles/l ethylbutyrylurea. These patients were comatose, apneic, had isoelectric encephalographic records and decreased body temperature. The degree of central nervous depression as judged by clinical signs was found to correlate with the serum concentrations of carbromal and of bromoethylbutyramide. Pharmacological activity and acute toxicity of carbromal and its two metabolites were examined in rats and compared with the activity of phenobarbitone. For intraperitoneal injection LD-50 values were found to be for carbromal 1.8 mmoles/kg, for bromoethylbutyramide 1.5 mmoles/kg, for ethylbutyrylurea 5.0 mmoles/kg and for phenobarbitone 0.9 mmoles/kg. Carbromal and bromoethylbutyramide severely decreased body temperature. The relative narcotic activity was estimated to be for carbromal = 100; bromoethylbutyramide = 66; ethylbutyrylurea = 33; phenobarbitone = 100. The anticonvulsive activity against pentetrazol-induced generalized seizures was nearly identical for carbromal, bromoethylbutyramide and phenobarbitone. Anticonvulsant activity of ethylbutyrylurea was two to three times less than that of carbromal. Inorganic bromide was found to increase the narcotic activity of carbromal and of bromoethylbutyramide. The findings show that the clinical signs of central nervous system depression seen in patients acutely poisoned with carbromal are caused mainly by unchanged carbromal and by its metabolite bromoethylbutyramide.", "contents": "[On the toxicology of carbromal. III. Role of active metabolites in humans acutely poisoned with carbromal-containing sedatives (author's transl)]. Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumoles/l, for bromoethylbutyramide up to 20 mumoles/l and for ethylbutyrylurea 2--3 mumoles/l. In patients acutely poisoned by carbromal-containing sedatives serum concentrations measured were in the range of 200 mumoles/l carbromal, 350 mumoles/l bromoethylbutyramide and 50 mumoles/l ethylbutyrylurea. These patients were comatose, apneic, had isoelectric encephalographic records and decreased body temperature. The degree of central nervous depression as judged by clinical signs was found to correlate with the serum concentrations of carbromal and of bromoethylbutyramide. Pharmacological activity and acute toxicity of carbromal and its two metabolites were examined in rats and compared with the activity of phenobarbitone. For intraperitoneal injection LD-50 values were found to be for carbromal 1.8 mmoles/kg, for bromoethylbutyramide 1.5 mmoles/kg, for ethylbutyrylurea 5.0 mmoles/kg and for phenobarbitone 0.9 mmoles/kg. Carbromal and bromoethylbutyramide severely decreased body temperature. The relative narcotic activity was estimated to be for carbromal = 100; bromoethylbutyramide = 66; ethylbutyrylurea = 33; phenobarbitone = 100. The anticonvulsive activity against pentetrazol-induced generalized seizures was nearly identical for carbromal, bromoethylbutyramide and phenobarbitone. Anticonvulsant activity of ethylbutyrylurea was two to three times less than that of carbromal. Inorganic bromide was found to increase the narcotic activity of carbromal and of bromoethylbutyramide. The findings show that the clinical signs of central nervous system depression seen in patients acutely poisoned with carbromal are caused mainly by unchanged carbromal and by its metabolite bromoethylbutyramide."}
{"id": "PMID:28111", "title": "Hepatotoxic effect of thioacetamide (TAM) on NADP-linked enzymes, aminotransferases and glutamate dehydrogenase.", "content": "NADP-linked dehydrogenases, glucose-6-P dehydrogenase (G 6PDH) 6-P gluconate dehydrogenase (6 PGDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase decarboxylating (ME) and aminotransferases GOT and GPT were analyzed in the soluble fraction of blood free homogenates. Glutmate dehydrogenase (GDH) was assayed in the mitochondrial fraction. TAM was i.p. administered to male albino rats (50 mg/kg/day) for 28 days. enzyme activities were determined as described by Bermeyer 1965 (Methods Enzymatic Analysis. Verlag Chemie. Acad. Press).", "contents": "Hepatotoxic effect of thioacetamide (TAM) on NADP-linked enzymes, aminotransferases and glutamate dehydrogenase. NADP-linked dehydrogenases, glucose-6-P dehydrogenase (G 6PDH) 6-P gluconate dehydrogenase (6 PGDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase decarboxylating (ME) and aminotransferases GOT and GPT were analyzed in the soluble fraction of blood free homogenates. Glutmate dehydrogenase (GDH) was assayed in the mitochondrial fraction. TAM was i.p. administered to male albino rats (50 mg/kg/day) for 28 days. enzyme activities were determined as described by Bermeyer 1965 (Methods Enzymatic Analysis. Verlag Chemie. Acad. Press)."}
{"id": "PMID:28112", "title": "Changes in liver tyrosine aminotransferase after acute and chronic administration of morphine in the rat.", "content": "Acute administration of Morphine (20 mg/kg/s.c.) in the rat results in a rise of liver tyrosine aminotransferase (TAT) expressed as mumoles of p-hydroxyphenylpyruvate/100 mg/h. With chronic administration, a tolerance develops to this enzymatic effect. TAT induction is not evident in pregnant rats, given the narcotic, in which enzyme levels are already initially high. After delivery TAT returns to normal levels and it is possible to show both induction and tolerance developing to morphine. Enzyme activity in fetal livers is much lower than that of adult animals: after maternal administration of morphine only a modest TAT increase is seen which is not, however, statistically significant. TAT activity is fully evident in livers of offspring, with much higher mean levels in newborn rats from morphine-treated animals, as a possible consequence of morphine deprivation. In this latter group of newborn rats narcotic administration causes TAT activity to return to levels as high as those of naive animals. On the other hand, morphine administration to the prole of naive rats results in an induction of liver TAT.", "contents": "Changes in liver tyrosine aminotransferase after acute and chronic administration of morphine in the rat. Acute administration of Morphine (20 mg/kg/s.c.) in the rat results in a rise of liver tyrosine aminotransferase (TAT) expressed as mumoles of p-hydroxyphenylpyruvate/100 mg/h. With chronic administration, a tolerance develops to this enzymatic effect. TAT induction is not evident in pregnant rats, given the narcotic, in which enzyme levels are already initially high. After delivery TAT returns to normal levels and it is possible to show both induction and tolerance developing to morphine. Enzyme activity in fetal livers is much lower than that of adult animals: after maternal administration of morphine only a modest TAT increase is seen which is not, however, statistically significant. TAT activity is fully evident in livers of offspring, with much higher mean levels in newborn rats from morphine-treated animals, as a possible consequence of morphine deprivation. In this latter group of newborn rats narcotic administration causes TAT activity to return to levels as high as those of naive animals. On the other hand, morphine administration to the prole of naive rats results in an induction of liver TAT."}
{"id": "PMID:28113", "title": "[Morphometric and electron microscopic study of the small intestine following total orthotopical auto- and allotransplantation].", "content": "Total orthotopic autotransplantation of the small intestine was performed in 22 dogs, allotransplantation--in 13 dogs. Changes in the wall of the graft resulted from the effect of both nonspecific (ischaemia, blockage of lymph outflow, denervation) and specific factors connected with the reaction of tissue incompatibility. Changes caused by the nonspecific factors are demonstrated as lymphostasis, edema of the wall in the graft, atrophy of the villi with epithelial flattening, hyperplasy of the intestinal gland, macrophagal and plasmocytic reaction in the mucous lamina propria, drop in villous-cryptic coefficient and reduction of the absorbing surface of the villi. At autotransplantation, structural-functional changes in the intestine undergo three stages: the stage of acute morphological changes and pronounced functional disturbances (up to 1,5 months); the stage of relative structural stabilization and gradual functional restoration (up to 6 months); the stage of atrophic-hyperplastic changes in the wall and decrease in functional activity of the intestinal graft (followed-up for 15 months). At allotransplantation, depending on the degree of cellular reaction and vascular changes, as well as on the localization of the process in the wall of the graft, a \"graft versus host\" reaction and a \"recipient versus graft\" reaction is demonstrated. Peculiar rosettes of plasmocytes have been described as a possible index of the reaction \"graft versus host\".", "contents": "[Morphometric and electron microscopic study of the small intestine following total orthotopical auto- and allotransplantation]. Total orthotopic autotransplantation of the small intestine was performed in 22 dogs, allotransplantation--in 13 dogs. Changes in the wall of the graft resulted from the effect of both nonspecific (ischaemia, blockage of lymph outflow, denervation) and specific factors connected with the reaction of tissue incompatibility. Changes caused by the nonspecific factors are demonstrated as lymphostasis, edema of the wall in the graft, atrophy of the villi with epithelial flattening, hyperplasy of the intestinal gland, macrophagal and plasmocytic reaction in the mucous lamina propria, drop in villous-cryptic coefficient and reduction of the absorbing surface of the villi. At autotransplantation, structural-functional changes in the intestine undergo three stages: the stage of acute morphological changes and pronounced functional disturbances (up to 1,5 months); the stage of relative structural stabilization and gradual functional restoration (up to 6 months); the stage of atrophic-hyperplastic changes in the wall and decrease in functional activity of the intestinal graft (followed-up for 15 months). At allotransplantation, depending on the degree of cellular reaction and vascular changes, as well as on the localization of the process in the wall of the graft, a \"graft versus host\" reaction and a \"recipient versus graft\" reaction is demonstrated. Peculiar rosettes of plasmocytes have been described as a possible index of the reaction \"graft versus host\"."}
{"id": "PMID:28114", "title": "[Morphological characteristics of acute respiratory tract diseases of mixed etiology in children].", "content": "The analysis of 30 etiologically deciphered (by the direct Coons method) autopsy observations of acute respiratory diseases in children under 8 is presented. Monoinfections were established only in 6 cases. Morphological examinations of respiratory organs in 24 cases of mixed acute respiratory diseases (associations of virus-bacteria and virus-Mycoplasma pneumoniae-diplostreptococcus) revealed marked circulatory disorders and desquamative, dystrophic, and inflammatory processes in segmental bronchi, bronchioles and alveoles. Morphometric studies demonstrated statistically significant differences in the cell composition of infiltrates of interalveolar septa in monoinfections and associated infections.", "contents": "[Morphological characteristics of acute respiratory tract diseases of mixed etiology in children]. The analysis of 30 etiologically deciphered (by the direct Coons method) autopsy observations of acute respiratory diseases in children under 8 is presented. Monoinfections were established only in 6 cases. Morphological examinations of respiratory organs in 24 cases of mixed acute respiratory diseases (associations of virus-bacteria and virus-Mycoplasma pneumoniae-diplostreptococcus) revealed marked circulatory disorders and desquamative, dystrophic, and inflammatory processes in segmental bronchi, bronchioles and alveoles. Morphometric studies demonstrated statistically significant differences in the cell composition of infiltrates of interalveolar septa in monoinfections and associated infections."}
{"id": "PMID:28115", "title": "The effect of cryptorchidism on the quantitative histology, histochemistry and hydrolytic enzyme activity of the rat testis.", "content": "Cryptorchidism of the mature rat testis led to degeneration of the seminiferous tubules and changes in enzyme patterns and activities. Spermatogenic stages 1-4, containing pachytene primary spermatocytes in late meiotic prophase, and stage 5, containing recently formed round spermatids, were damaged by 48 h. Within 96 h stages showed a loss of germinal cells into the lumen and this was almost complete by 192 h. Acid phosphatase showed increased histochemical activity in the basal area of the seminiferous tubule up to 96 h of cryptorchidism, and at 192 h much of the activity was located in large lipidcontaining bodies within the remaining seminiferous epithelium. Total and free biochemical acid phosphatase decreased during cryptorchidism in parallel with cell loss; there were no significant changes in total cathepsin D activity but free enzyme activity was increased throughout the experimental period indicating increased lability of lysosomes in the Sertoli cell. Lactate dehydrogenase activity was mainly tubular but  succinate dehydrogenase also showed interstitial activity. Lipoamide dehydrogenase (NADH) was found mainly in the interstitium. During cryptorchidism both lactate and succinate dehydrogenase activity decreased in the tubules parallel to the loss of germinal cells, whereas lipoamide dehydrogenase (NADH) activity increased in both interstitial and tubular areas. It is suggested that the initial lesion in the seminiferous epithelium, produced by cryptorchidism is in the Sertoli cell and that germ cell damage may result from reduced function of the Sertoli cell.", "contents": "The effect of cryptorchidism on the quantitative histology, histochemistry and hydrolytic enzyme activity of the rat testis. Cryptorchidism of the mature rat testis led to degeneration of the seminiferous tubules and changes in enzyme patterns and activities. Spermatogenic stages 1-4, containing pachytene primary spermatocytes in late meiotic prophase, and stage 5, containing recently formed round spermatids, were damaged by 48 h. Within 96 h stages showed a loss of germinal cells into the lumen and this was almost complete by 192 h. Acid phosphatase showed increased histochemical activity in the basal area of the seminiferous tubule up to 96 h of cryptorchidism, and at 192 h much of the activity was located in large lipidcontaining bodies within the remaining seminiferous epithelium. Total and free biochemical acid phosphatase decreased during cryptorchidism in parallel with cell loss; there were no significant changes in total cathepsin D activity but free enzyme activity was increased throughout the experimental period indicating increased lability of lysosomes in the Sertoli cell. Lactate dehydrogenase activity was mainly tubular but  succinate dehydrogenase also showed interstitial activity. Lipoamide dehydrogenase (NADH) was found mainly in the interstitium. During cryptorchidism both lactate and succinate dehydrogenase activity decreased in the tubules parallel to the loss of germinal cells, whereas lipoamide dehydrogenase (NADH) activity increased in both interstitial and tubular areas. It is suggested that the initial lesion in the seminiferous epithelium, produced by cryptorchidism is in the Sertoli cell and that germ cell damage may result from reduced function of the Sertoli cell."}
{"id": "PMID:28118", "title": "Rudimentary locus of Drosophila melanogaster: partial purification of a carbamylphosphate synthase--aspartate transcarbamylase--dihydroorotase complex.", "content": "Glutamine-dependent CPSase, ATCase, and DHOase from Drosophila, the first three enzymes in pyrimidine biosynthesis, show coordinate variation in activity throughout development. The three activities were highest in first instar larvae and decreased as development proceeded. The three activities cosediment in sucrose gradients as a single peak with a relative sedimentation coefficient of approximately 30S. CPSase, ATCase, and DHOase copurify during (NH4)2SO4 fractionation and during DEAE-cellulose and hydroxylapatite chromatography.", "contents": "Rudimentary locus of Drosophila melanogaster: partial purification of a carbamylphosphate synthase--aspartate transcarbamylase--dihydroorotase complex. Glutamine-dependent CPSase, ATCase, and DHOase from Drosophila, the first three enzymes in pyrimidine biosynthesis, show coordinate variation in activity throughout development. The three activities were highest in first instar larvae and decreased as development proceeded. The three activities cosediment in sucrose gradients as a single peak with a relative sedimentation coefficient of approximately 30S. CPSase, ATCase, and DHOase copurify during (NH4)2SO4 fractionation and during DEAE-cellulose and hydroxylapatite chromatography."}
{"id": "PMID:28119", "title": "Genetics and physiological expression of beta-hydroxy acid dehydrogenase in Drosophila.", "content": "A mutant Hadnl was induced in Drosophila melanogaster and found to be deficient in beta-hydroxy acid dehydrogenase. This mutation was utilized to study the genetics and physiological expression of Had+ . Had+ was mapped to the X chromosome at 54.4 and seems to be the structural gene for the enzyme. Enzyme activity in male and female flies indicates that the gene shows both dosage compensation independent from dose effect and differential activity during ontogeny. Electrophoretic mobility data indicate that the enzyme is a dimer which forms by random association of subunits. The fact that the mutant shows no detrimental effect implies that the enzyme is dispensable, at least under laboratory conditions. The biological and technical implications of this gene--enzyme system are discussed.", "contents": "Genetics and physiological expression of beta-hydroxy acid dehydrogenase in Drosophila. A mutant Hadnl was induced in Drosophila melanogaster and found to be deficient in beta-hydroxy acid dehydrogenase. This mutation was utilized to study the genetics and physiological expression of Had+ . Had+ was mapped to the X chromosome at 54.4 and seems to be the structural gene for the enzyme. Enzyme activity in male and female flies indicates that the gene shows both dosage compensation independent from dose effect and differential activity during ontogeny. Electrophoretic mobility data indicate that the enzyme is a dimer which forms by random association of subunits. The fact that the mutant shows no detrimental effect implies that the enzyme is dispensable, at least under laboratory conditions. The biological and technical implications of this gene--enzyme system are discussed."}
{"id": "PMID:28133", "title": "Pharmacokinetics of fazadinium in man.", "content": "The disposition of fazadinium was studied in 10 patients with normal hepatic and renal function undergoing abdominal surgery. The serum and urinary concentrations were determined fluorimetrically. A single dose of fazadinium 1.5 mg kg-1 was administered i.v. The plasma decay curve for fazadinium was found to be diphasic and the data were interpreted according to a two-compartment open model. The half-lives of the distribution and elimination phases were 12.3 and 76.4 min respectively. The total apparent volume of distribution averaged 234 ml kg-1 and the plasma clearance 132 ml min-1. From these results it is suggested that fazadinium should have a shorter duration of action than other non-depolarizing agents because of the more rapid decline of the serum concentration corresponding mainly to the short half-life of the beta phase. This rapid elimination phase of fazadinium did not correspond to an extensive biotransformation because fazadinium was excreted almost unchanged in the urine and this excretion accounted for 50% of the injected dose within 24 h.", "contents": "Pharmacokinetics of fazadinium in man. The disposition of fazadinium was studied in 10 patients with normal hepatic and renal function undergoing abdominal surgery. The serum and urinary concentrations were determined fluorimetrically. A single dose of fazadinium 1.5 mg kg-1 was administered i.v. The plasma decay curve for fazadinium was found to be diphasic and the data were interpreted according to a two-compartment open model. The half-lives of the distribution and elimination phases were 12.3 and 76.4 min respectively. The total apparent volume of distribution averaged 234 ml kg-1 and the plasma clearance 132 ml min-1. From these results it is suggested that fazadinium should have a shorter duration of action than other non-depolarizing agents because of the more rapid decline of the serum concentration corresponding mainly to the short half-life of the beta phase. This rapid elimination phase of fazadinium did not correspond to an extensive biotransformation because fazadinium was excreted almost unchanged in the urine and this excretion accounted for 50% of the injected dose within 24 h."}
{"id": "PMID:28128", "title": "Pharmacokinetics of sulphamethoxazole in man: effects of urinary pH and urine flow on metabolism and renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole.", "content": "A high performance liquid chromatography method for the determination of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole is described. The renal excretion rate and cumulative renal excretion of sulphamethoxazole is markedly influenced by urinary pH. With constant urinary pH, the renal excretion rate and the renal clearance of sulphamethoxazole is dependent on the urine flow. The renal clearance of the metabolite N4-acetylsulphamethoxazole is not influenced by urinary pH or urine flow. No clear acetylator phenotype could be detected in the group of volunteers studied. The extent of acetylation depends on the amount of sulphamethoxazole available for acetylation, thus indirectly on the urine pH and flow.", "contents": "Pharmacokinetics of sulphamethoxazole in man: effects of urinary pH and urine flow on metabolism and renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole. A high performance liquid chromatography method for the determination of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole is described. The renal excretion rate and cumulative renal excretion of sulphamethoxazole is markedly influenced by urinary pH. With constant urinary pH, the renal excretion rate and the renal clearance of sulphamethoxazole is dependent on the urine flow. The renal clearance of the metabolite N4-acetylsulphamethoxazole is not influenced by urinary pH or urine flow. No clear acetylator phenotype could be detected in the group of volunteers studied. The extent of acetylation depends on the amount of sulphamethoxazole available for acetylation, thus indirectly on the urine pH and flow."}
{"id": "PMID:28134", "title": "The use of chlorazepate for premedication on the night before surgery.", "content": "Chlorazepate, a long-acting benzodiazepine, allayed anxiety before operation, being superior to placebo in a double-blind study in which the drug was given the night before surgery. Long-term relief of apprehension before surgery by the administration of chlorazepate, combined with a narcotic analgesic when indicated, is advocated.", "contents": "The use of chlorazepate for premedication on the night before surgery. Chlorazepate, a long-acting benzodiazepine, allayed anxiety before operation, being superior to placebo in a double-blind study in which the drug was given the night before surgery. Long-term relief of apprehension before surgery by the administration of chlorazepate, combined with a narcotic analgesic when indicated, is advocated."}
{"id": "PMID:28135", "title": "Comparative peripheral and coronary haemodynamic effects of rimiterol and isoprenaline.", "content": "1. Rimiterol and isoprenaline produced significant dose-related increases in cardiac output. 2. These changes in cardiac output were accompanied by increases in heart rate and myocardial oxygen consumption which were similar for each drug and dose-related. 3. Isoprenaline in contrast with rimiterol produced direct coronary vasodilation, i.e. coronary vasodilation in excess of that required to meet increases in myocardial oxygen demands. 4. It is suggested that the beta-adrenergic receptors in the human coronary vasculature are mainly of the beta1 type. 5. Rimiterol, because it does not produce direct coronary vasodilation may be preferable to isoprenaline in the treatment of low-cardiac output syndrome where there is regional myocardial ischaemia, since it would be less likely to produce a \"coronary steal\" effect.", "contents": "Comparative peripheral and coronary haemodynamic effects of rimiterol and isoprenaline. 1. Rimiterol and isoprenaline produced significant dose-related increases in cardiac output. 2. These changes in cardiac output were accompanied by increases in heart rate and myocardial oxygen consumption which were similar for each drug and dose-related. 3. Isoprenaline in contrast with rimiterol produced direct coronary vasodilation, i.e. coronary vasodilation in excess of that required to meet increases in myocardial oxygen demands. 4. It is suggested that the beta-adrenergic receptors in the human coronary vasculature are mainly of the beta1 type. 5. Rimiterol, because it does not produce direct coronary vasodilation may be preferable to isoprenaline in the treatment of low-cardiac output syndrome where there is regional myocardial ischaemia, since it would be less likely to produce a \"coronary steal\" effect."}
{"id": "PMID:28142", "title": "13C nuclear magnetic resonance study of the cis-trans isomerism in X-Pro-Pro tripeptides.", "content": "13C nuclear magnetic resonance has been used to characterize quantitatively the cis-trans isomerism about both peptide bonds in the tripeptides Ser-Pro-Pro and Arg-Pro-Pro. Detailed pH titration data indicate that the configuration about both peptide bonds is closely linked to titration of the terminal carboxyl group and, to a lesser extent, to titration of the terminal amino group. The Pro2 C-3 resonance has been found particularly useful for interpretation due to its sensitivity to the isomerization about both peptide bonds. Analysis of the probabilities of the trans-trans, cic-cis, cis-trans, and trans-cis isomers in aqueous solution indicates a stability decrease in the order given. Similarities in the isomerization behavior of the two peptides indicate that side chain interactions involving the first residue have very little effect on the observed cis/trans ratios. The sensitivity of the cis/trans ratio to titration of the terminal amino group is most readily explained on the basis of an indirect effect on carbonyl-carbonyl repulsion.", "contents": "13C nuclear magnetic resonance study of the cis-trans isomerism in X-Pro-Pro tripeptides. 13C nuclear magnetic resonance has been used to characterize quantitatively the cis-trans isomerism about both peptide bonds in the tripeptides Ser-Pro-Pro and Arg-Pro-Pro. Detailed pH titration data indicate that the configuration about both peptide bonds is closely linked to titration of the terminal carboxyl group and, to a lesser extent, to titration of the terminal amino group. The Pro2 C-3 resonance has been found particularly useful for interpretation due to its sensitivity to the isomerization about both peptide bonds. Analysis of the probabilities of the trans-trans, cic-cis, cis-trans, and trans-cis isomers in aqueous solution indicates a stability decrease in the order given. Similarities in the isomerization behavior of the two peptides indicate that side chain interactions involving the first residue have very little effect on the observed cis/trans ratios. The sensitivity of the cis/trans ratio to titration of the terminal amino group is most readily explained on the basis of an indirect effect on carbonyl-carbonyl repulsion."}
{"id": "PMID:28146", "title": "Enzymatic basis for the Ca2+-induced cross-linking of membrane proteins in intact human erythrocytes.", "content": "The accumulation of Ca2+ ions in intact human erythrocytes leads to the production of membrane protein polymers larger than spectrin. The polymer has a heterogeneous size distribution and is rich in gamma-glutamyl-epsilon-lysine cross-links. Isolation of this isodipeptide, in amounts as high as 6 mol/10(5) g of protein, confirms the idea [Lorand L., Weissmann, L.B., Epel, D.L., and Bruner-Lorand, J. (1976), Proc. Natl. Acad. Sci. U.S.A. 73, 4479] that the Ca2+-induced membrane protein polymerization is mediated by transglutaminase. Formation of the polymer in the intact cells is inhibited by the addition of small, water-soluble primary amines. Inasmuch as these amines are known to prevent the Ca2+-dependent loss of deformability of the membrane, it is suggested that transglutaminase-catalyzed cross-linking may be a biochemical cause of irreversible membrane stiffening.", "contents": "Enzymatic basis for the Ca2+-induced cross-linking of membrane proteins in intact human erythrocytes. The accumulation of Ca2+ ions in intact human erythrocytes leads to the production of membrane protein polymers larger than spectrin. The polymer has a heterogeneous size distribution and is rich in gamma-glutamyl-epsilon-lysine cross-links. Isolation of this isodipeptide, in amounts as high as 6 mol/10(5) g of protein, confirms the idea [Lorand L., Weissmann, L.B., Epel, D.L., and Bruner-Lorand, J. (1976), Proc. Natl. Acad. Sci. U.S.A. 73, 4479] that the Ca2+-induced membrane protein polymerization is mediated by transglutaminase. Formation of the polymer in the intact cells is inhibited by the addition of small, water-soluble primary amines. Inasmuch as these amines are known to prevent the Ca2+-dependent loss of deformability of the membrane, it is suggested that transglutaminase-catalyzed cross-linking may be a biochemical cause of irreversible membrane stiffening."}
{"id": "PMID:28148", "title": "Effects of substituents on the rates of deacylation of substituted benzoyl papains. Role of a carboxylate residue in the catalytic mechanism.", "content": "The effect of ring substituents on the rates of deacylation of 8 meta- and para-substituted benzoyl papains was evaluated. The rate constants were found to depend upon a single ionizing group of pKa = 4.2--4.3, and to decrease by a factor of approximately 2.2 when measured in 94% D2O/H2O. The rates of deacylation are increased greatly by electron-withdrawing groups on the benzene ring. The Hammett rho value is 2.74 +/- 0.32. A plot of the rate constants for deacylation of the benzoyl papains against the corresponding constants for substituted benzoyl chymotrypsins generates a straight line of slope 1.0. This result suggests a very similar distribution of charge on the benzoyl moiety in the transition state for the two enzymes, which is interpreted in terms of the net charge of the transition state for the deacylation of nonspecific acyl papains being equal to--1 with the general base catalyzed assistance to the attack of water on the acyl enzyme being provided by the negatively charged Asp-158 rather than by the neutral Asn-175-His-159 hydrogen bond network. This result together with a survey of literature data suggests that the role of Asp-158 in papain catalysis has been underestimated. The evidence advanced to date in support of the proposition that an imidazolium-159-cysteine-25 thiolate ion pair exists in native papain is evaluated and considered to be insufficient to decide the issue.", "contents": "Effects of substituents on the rates of deacylation of substituted benzoyl papains. Role of a carboxylate residue in the catalytic mechanism. The effect of ring substituents on the rates of deacylation of 8 meta- and para-substituted benzoyl papains was evaluated. The rate constants were found to depend upon a single ionizing group of pKa = 4.2--4.3, and to decrease by a factor of approximately 2.2 when measured in 94% D2O/H2O. The rates of deacylation are increased greatly by electron-withdrawing groups on the benzene ring. The Hammett rho value is 2.74 +/- 0.32. A plot of the rate constants for deacylation of the benzoyl papains against the corresponding constants for substituted benzoyl chymotrypsins generates a straight line of slope 1.0. This result suggests a very similar distribution of charge on the benzoyl moiety in the transition state for the two enzymes, which is interpreted in terms of the net charge of the transition state for the deacylation of nonspecific acyl papains being equal to--1 with the general base catalyzed assistance to the attack of water on the acyl enzyme being provided by the negatively charged Asp-158 rather than by the neutral Asn-175-His-159 hydrogen bond network. This result together with a survey of literature data suggests that the role of Asp-158 in papain catalysis has been underestimated. The evidence advanced to date in support of the proposition that an imidazolium-159-cysteine-25 thiolate ion pair exists in native papain is evaluated and considered to be insufficient to decide the issue."}
{"id": "PMID:28149", "title": "The status of tyrosyl residues in a Formosan cobra cardiotoxin.", "content": "Spectrophotometric titration of Formosan cobra cardiotoxin showed that two of the three tyrosyl residues were titrated freely with a normal apparent pKa of 9.6 whereas the remaining one ionized at pH above 11.0. Nitration of cardiotoxin in Tris . HCl buffer with tetranitromethane resulted in the selective nitration of tyrosine 11 and tyrosine 22. It also revealed that tyrosine 51 was the abnormal one in the spectrophotometric titration. Complete nitration occurred in the presence of 6.0 M guanidine hydrochloride. Compared with the conformation of native cardiotoxin, the peptide conformation of the partially nitrated cardiotoxin did not change significantly but the conformation of the completely nitrated cardiotoxin changed remarkably. The biological activity of cardiotoxin was indeed affected by nitration, but the immunological activity was nearly intact even when all the tyrosine residues were nitrated.", "contents": "The status of tyrosyl residues in a Formosan cobra cardiotoxin. Spectrophotometric titration of Formosan cobra cardiotoxin showed that two of the three tyrosyl residues were titrated freely with a normal apparent pKa of 9.6 whereas the remaining one ionized at pH above 11.0. Nitration of cardiotoxin in Tris . HCl buffer with tetranitromethane resulted in the selective nitration of tyrosine 11 and tyrosine 22. It also revealed that tyrosine 51 was the abnormal one in the spectrophotometric titration. Complete nitration occurred in the presence of 6.0 M guanidine hydrochloride. Compared with the conformation of native cardiotoxin, the peptide conformation of the partially nitrated cardiotoxin did not change significantly but the conformation of the completely nitrated cardiotoxin changed remarkably. The biological activity of cardiotoxin was indeed affected by nitration, but the immunological activity was nearly intact even when all the tyrosine residues were nitrated."}
{"id": "PMID:28150", "title": "Spectroscopic studies on the tyrosine residues of canavalin.", "content": "Canavalin is a tetramer with 6 tyrosines per subunit. In the work presented here, we have classified these tyrosines by their spectrophotometric and fluorometric pH titration and their ability to be quenched I-. Of the 6 residues, 2 were found to be exposed to the solvent. One (pK = 10.2) contributes 28% of the total fluorescence intensity; the second has a pK of 11.50, and a lower quantum yield, contributing only 16% of the total intensity. The remaining 4 residues (pK = 12.5, contributing 54% of fluorescence intensity) are buried; their titration is irreversible, requiring protein denaturation.", "contents": "Spectroscopic studies on the tyrosine residues of canavalin. Canavalin is a tetramer with 6 tyrosines per subunit. In the work presented here, we have classified these tyrosines by their spectrophotometric and fluorometric pH titration and their ability to be quenched I-. Of the 6 residues, 2 were found to be exposed to the solvent. One (pK = 10.2) contributes 28% of the total fluorescence intensity; the second has a pK of 11.50, and a lower quantum yield, contributing only 16% of the total intensity. The remaining 4 residues (pK = 12.5, contributing 54% of fluorescence intensity) are buried; their titration is irreversible, requiring protein denaturation."}
{"id": "PMID:28152", "title": "Proton NMR studies on soya bean lipoxygenase-1.", "content": "The 270 MHz 1H-NMR spectrum of soya bean lipoxygenase-1 (linoleate: oxygen oxidoreductase, EC 1.13.11.12) was investigated at 298 K and at several pH values. A large fraction of the protein (50%) was found to be effectively random coil.", "contents": "Proton NMR studies on soya bean lipoxygenase-1. The 270 MHz 1H-NMR spectrum of soya bean lipoxygenase-1 (linoleate: oxygen oxidoreductase, EC 1.13.11.12) was investigated at 298 K and at several pH values. A large fraction of the protein (50%) was found to be effectively random coil."}
{"id": "PMID:28153", "title": "[Role of the electron acceptor properties of lysozyme and its substrate inhibitors in photosensitized electron transport in their complexes by the EPR method].", "content": "The nature of electron-acceptor groups in the system of lysozyme with its substrate-inhibitors has been studied in a wide range of pH values by the method of photosensitized electron transfer. In the lysozyme molecule disulphide bonds and peptide groups are the electron--acceptor groups. The nature of radicals in irradiated lysozyme depends on pH. At complex-formation of lysozyme with oligomeres of N-acetylglucosamine the electron transfer from the enzyme molecule to N-acetyl group of the substrate-inhibitor molecule is realized. Under conditions ruling out complex-formation of lysozyme with the inhibitors (N-acetylglucosamine and its dimer) the electrons are localized on disulphide bonds of the protein molecules at alkaline pH and at pH less than or equal to 3 the radicals are observed which are due to the remove of hydrogen atom from the Calpha-atom of the protein polypeptide chain.", "contents": "[Role of the electron acceptor properties of lysozyme and its substrate inhibitors in photosensitized electron transport in their complexes by the EPR method]. The nature of electron-acceptor groups in the system of lysozyme with its substrate-inhibitors has been studied in a wide range of pH values by the method of photosensitized electron transfer. In the lysozyme molecule disulphide bonds and peptide groups are the electron--acceptor groups. The nature of radicals in irradiated lysozyme depends on pH. At complex-formation of lysozyme with oligomeres of N-acetylglucosamine the electron transfer from the enzyme molecule to N-acetyl group of the substrate-inhibitor molecule is realized. Under conditions ruling out complex-formation of lysozyme with the inhibitors (N-acetylglucosamine and its dimer) the electrons are localized on disulphide bonds of the protein molecules at alkaline pH and at pH less than or equal to 3 the radicals are observed which are due to the remove of hydrogen atom from the Calpha-atom of the protein polypeptide chain."}
{"id": "PMID:28158", "title": "Sympathetic and parasympathetic control of heart rate in unanaesthetized fetal and newborn lambs.", "content": "Development of autonomic nervous control of basal heart rate was studied in unanesthetized fetal lambs (93 days to term) and newborn lambs (2--29 days), using atropine and/or propranolol blockade. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate; vagal influence in the newborn lamb was similar to the term fetus. Sympathetic stimulation of fetal heart rate declined toward term, possibly due to the strongly increasing parasympathetic influence. Sympathetic influence in the newborn was similar to the early-gestation fetus. Intrinsic heart rate was about 185 beats/min throughout the fetal and newborn life span studied. Thus changes in basal heart rate resulted from a different balance of the sympathetic and parasympathetic components of the autonomic nervous outflow.", "contents": "Sympathetic and parasympathetic control of heart rate in unanaesthetized fetal and newborn lambs. Development of autonomic nervous control of basal heart rate was studied in unanesthetized fetal lambs (93 days to term) and newborn lambs (2--29 days), using atropine and/or propranolol blockade. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate; vagal influence in the newborn lamb was similar to the term fetus. Sympathetic stimulation of fetal heart rate declined toward term, possibly due to the strongly increasing parasympathetic influence. Sympathetic influence in the newborn was similar to the early-gestation fetus. Intrinsic heart rate was about 185 beats/min throughout the fetal and newborn life span studied. Thus changes in basal heart rate resulted from a different balance of the sympathetic and parasympathetic components of the autonomic nervous outflow."}
{"id": "PMID:28154", "title": "[Structural changes in cell nuclei in the physiologic pH range].", "content": "Fluorescence of the suspension of cell nuclei from rat liver was investigated under neutral pH range. The pH decrease from 7 to 5 causes the quenching of protein fluorescence of nuclei and leads to an increase of the polarization degree of the fluorescence. Buffering properties of the nuclei in this range were detected. The use of 1-anilino-8-naphthalenesulfonate as the fluorescent probe permits to find the changes of nuclei surface properties with increasing the proton concentration in the solution. Circular dichroism spectra of nuclei were shown to depend on the pH solution too. It was suggested that structure state of the nuclei depends on the pH solution. The structural changes are reversible in the physiological pH range and were concluded to be in the envelope and chromatin of the nuclei. The role of histidine residues of nuclear proteins in the initiation of the structure changes was discussed. It was supposed that structure changes of the nuclei in the physiological pH range have an essential functional role.", "contents": "[Structural changes in cell nuclei in the physiologic pH range]. Fluorescence of the suspension of cell nuclei from rat liver was investigated under neutral pH range. The pH decrease from 7 to 5 causes the quenching of protein fluorescence of nuclei and leads to an increase of the polarization degree of the fluorescence. Buffering properties of the nuclei in this range were detected. The use of 1-anilino-8-naphthalenesulfonate as the fluorescent probe permits to find the changes of nuclei surface properties with increasing the proton concentration in the solution. Circular dichroism spectra of nuclei were shown to depend on the pH solution too. It was suggested that structure state of the nuclei depends on the pH solution. The structural changes are reversible in the physiological pH range and were concluded to be in the envelope and chromatin of the nuclei. The role of histidine residues of nuclear proteins in the initiation of the structure changes was discussed. It was supposed that structure changes of the nuclei in the physiological pH range have an essential functional role."}
{"id": "PMID:28159", "title": "Fundamental aspects of antimony thin film electrodes for pH measurement.", "content": "This report concerns the investigation of the sensitivity, temperature dependence, accuracy, and the standard electrode potential EO of an antimony thin film pH electrode which was prepared with electron beam evaporation techniques. The air-formed oxide film on antimony thin film electrodes has been proved by both the cathodic reduction method and electron spectroscopy for chemical analysis (ESCA). The antimony thin film electrode responded rapidly to pH changes and its sensitivity was slightly changed depending on the buffer composition. The accuracy of this electrode was compared with that of the glass electrode. Temperature had some influence on the function of this electrode. The standard electrode potential of this electrode was discussed together with that of other forms of antimony electrodes. The structure and thickness of the surface oxide on antimony thin film electrodes was confirmed by cathodic reduction and ESCA. It was clear that the surface oxide governs the electrode reactions. Possible applications of the antimony thin film electrode are discussed stating some limitations in the use.", "contents": "Fundamental aspects of antimony thin film electrodes for pH measurement. This report concerns the investigation of the sensitivity, temperature dependence, accuracy, and the standard electrode potential EO of an antimony thin film pH electrode which was prepared with electron beam evaporation techniques. The air-formed oxide film on antimony thin film electrodes has been proved by both the cathodic reduction method and electron spectroscopy for chemical analysis (ESCA). The antimony thin film electrode responded rapidly to pH changes and its sensitivity was slightly changed depending on the buffer composition. The accuracy of this electrode was compared with that of the glass electrode. Temperature had some influence on the function of this electrode. The standard electrode potential of this electrode was discussed together with that of other forms of antimony electrodes. The structure and thickness of the surface oxide on antimony thin film electrodes was confirmed by cathodic reduction and ESCA. It was clear that the surface oxide governs the electrode reactions. Possible applications of the antimony thin film electrode are discussed stating some limitations in the use."}
{"id": "PMID:28162", "title": "[Use of acetylcholinesterase reactivators and central cholinolytics in the treatment of experimental tetanus poisoning].", "content": "Experiments were conducted on rabbits with tetanus intoxication induced by the intravenous injection of a lethal dose of the toxin; a study was made of the therapeutic efficacy of the acetylcholinesterase reactivators--dipyroxim and isonitrosine, and also of the central cholinolytics--amizyl and diphacyl. In dose of 25 mg/kg dipyroxim produced no therapeutic effect, and in doses of 30--40 mg/kg caused the animal death. Amizyl and diphacil in a dose of 3--4 mg/kg caused elimination of tonic convulsions for 1 1/2--2 hours. As to isonitrosin--it produced the same effect for 4--5 hours. In case of combined administration of reactivators and cholinolytics convulsions were eliminated for 4--5 hours.", "contents": "[Use of acetylcholinesterase reactivators and central cholinolytics in the treatment of experimental tetanus poisoning]. Experiments were conducted on rabbits with tetanus intoxication induced by the intravenous injection of a lethal dose of the toxin; a study was made of the therapeutic efficacy of the acetylcholinesterase reactivators--dipyroxim and isonitrosine, and also of the central cholinolytics--amizyl and diphacyl. In dose of 25 mg/kg dipyroxim produced no therapeutic effect, and in doses of 30--40 mg/kg caused the animal death. Amizyl and diphacil in a dose of 3--4 mg/kg caused elimination of tonic convulsions for 1 1/2--2 hours. As to isonitrosin--it produced the same effect for 4--5 hours. In case of combined administration of reactivators and cholinolytics convulsions were eliminated for 4--5 hours."}
{"id": "PMID:28166", "title": "Prediction of wound sepsis following gastric operations.", "content": "Gastric aspirates were obtained from 12 healthy volunteers, 49 patients with duodenal ulcer, 14 with gastric ulcer and 35 with gastric carcinoma. The mean total viable bacterial counts in these groups were as follows: volunteers 0, duodenal ulcer 3.8 X 10(1), gastric ulcer 6.95 X 10(4), carcinoma 1.9 X 10(7) organisms/ml. The incidence of wound sepsis in patients without antibiotic cover was; duodenal ulcer 17 per cent, gastric ulcer 38 per cent, carcinoma 56 per cent. Regardless of the underlying pathology, patients with counts greater than 5 X 10(6) organisms/ml in the gastric aspirate had a 93 per cent incidence of wound sepsis, compared with 16 per cent in patients with counts of less than 5 X 10(6) organisms/ml (P less than 0.001). In the group with high counts all except one of the wound infections were caused by organisms present in the stomach at the time of operation. There was a good correlation in the bacteriology of apirates obtained during preoperative endoscopy compared with operative nasogastric samples (n = 31) both for viable counts (r = 0.93) and for the counts of individual organisms. Therefore, preoperative endoscopy can be used to identify patients who are at risk of developing wound sepsis after gastric surgery.", "contents": "Prediction of wound sepsis following gastric operations. Gastric aspirates were obtained from 12 healthy volunteers, 49 patients with duodenal ulcer, 14 with gastric ulcer and 35 with gastric carcinoma. The mean total viable bacterial counts in these groups were as follows: volunteers 0, duodenal ulcer 3.8 X 10(1), gastric ulcer 6.95 X 10(4), carcinoma 1.9 X 10(7) organisms/ml. The incidence of wound sepsis in patients without antibiotic cover was; duodenal ulcer 17 per cent, gastric ulcer 38 per cent, carcinoma 56 per cent. Regardless of the underlying pathology, patients with counts greater than 5 X 10(6) organisms/ml in the gastric aspirate had a 93 per cent incidence of wound sepsis, compared with 16 per cent in patients with counts of less than 5 X 10(6) organisms/ml (P less than 0.001). In the group with high counts all except one of the wound infections were caused by organisms present in the stomach at the time of operation. There was a good correlation in the bacteriology of apirates obtained during preoperative endoscopy compared with operative nasogastric samples (n = 31) both for viable counts (r = 0.93) and for the counts of individual organisms. Therefore, preoperative endoscopy can be used to identify patients who are at risk of developing wound sepsis after gastric surgery."}
{"id": "PMID:28174", "title": "Characteristics of Thiobacillus thioparus and its thiocyanate assimilation.", "content": "Thiocyanate-assimilatig bacterium, TK 21, was isolated from activated sludge used for the treatment of thiocyanate contained in coke-oven liquor. This organism oxidized thiosulfate and elemental sulfur, causing a decrease of pH of the medium. These facts indicated that it belongs to the genus Thiobacillus. Potassium thiocyanate (0.5 g/l) was completely assimilated during 60 h. Thiosulfate inhibited the assimilation of thiocyanate but elemental sulfur did not. This bacterium did not evolve cyanide as its oxidation product after the decomposition of thiocyanate. The isoalted bacterium was identified as Thiobacillus thioparus. Examination of the composition of cellular fatty acid of three strains of T. thioparus showed that they prossessed 3-hydroxy fatty acid of C10 and C12; saturated straight chains of C10, C12, C15, C16, C17, and C18; monounsaturated straight chains of C16 and C18; and cyclopropane acid of C17.", "contents": "Characteristics of Thiobacillus thioparus and its thiocyanate assimilation. Thiocyanate-assimilatig bacterium, TK 21, was isolated from activated sludge used for the treatment of thiocyanate contained in coke-oven liquor. This organism oxidized thiosulfate and elemental sulfur, causing a decrease of pH of the medium. These facts indicated that it belongs to the genus Thiobacillus. Potassium thiocyanate (0.5 g/l) was completely assimilated during 60 h. Thiosulfate inhibited the assimilation of thiocyanate but elemental sulfur did not. This bacterium did not evolve cyanide as its oxidation product after the decomposition of thiocyanate. The isoalted bacterium was identified as Thiobacillus thioparus. Examination of the composition of cellular fatty acid of three strains of T. thioparus showed that they prossessed 3-hydroxy fatty acid of C10 and C12; saturated straight chains of C10, C12, C15, C16, C17, and C18; monounsaturated straight chains of C16 and C18; and cyclopropane acid of C17."}
{"id": "PMID:28175", "title": "Oxidation of gallium sulfides by Thiobacillus ferrooxidans.", "content": "The bacterial oxidation of naturally occurring gallium-bearing chalcopyrite concentrate and a pure synthetic gallium (III) sulfide has been investigated at pH 1.8 and 35 degree C, using an active culture of Thiobacillus ferrooxidans. This oxidation process may proceed by direct or by indirect bacterial action. The highest dissolved gallium and copper concentrations were about 2.2 and 40.2 g/l, respectively. The order of the specific rate of oxygen uptake by T. ferrooxidans in approximately CuFES2 greater than or equal to gallium-bearing CuFeS2 greater than FeS2 greater than Cu2S greater than Cu2S greater than Ga2S3.", "contents": "Oxidation of gallium sulfides by Thiobacillus ferrooxidans. The bacterial oxidation of naturally occurring gallium-bearing chalcopyrite concentrate and a pure synthetic gallium (III) sulfide has been investigated at pH 1.8 and 35 degree C, using an active culture of Thiobacillus ferrooxidans. This oxidation process may proceed by direct or by indirect bacterial action. The highest dissolved gallium and copper concentrations were about 2.2 and 40.2 g/l, respectively. The order of the specific rate of oxygen uptake by T. ferrooxidans in approximately CuFES2 greater than or equal to gallium-bearing CuFeS2 greater than FeS2 greater than Cu2S greater than Cu2S greater than Ga2S3."}
{"id": "PMID:28178", "title": "Cyclophosphamide-induced oncogenic transformation, chromosomal breakage, and sister chromatid exchange following microsomal activation.", "content": "Cyclophosphamide, an extensively used cancer chemotherapeutic agent, requires metabolic activation through a mixed-function oxygenase system. The capacity of this agent to produce oncogenic transformation and chromosomal damage, including increases in sister chromatid exchanges, was investigated in cell culture with or without an exogenous liver metabolic activation system. No oncogenic transformation or chromosomal aberrations were produced by cyclophosphamide in the absence of metabolic activation, whereas significant transformation, chromosomal breaks, and increases in sister chromatid exchanges were observed when the activation system was incorporated into the assays. The oncogenic transformation and chromosomal changes were completely eliminated by removing glucose 6-phosphate and nicotinamide adenine dinucleotide phosphate from the metabolic generating system. These studies emphasize the necessity to incorporate some activation procedure into short-term assays used for evaluating the mutagenic and/or oncogenic potential of various chemicals.", "contents": "Cyclophosphamide-induced oncogenic transformation, chromosomal breakage, and sister chromatid exchange following microsomal activation. Cyclophosphamide, an extensively used cancer chemotherapeutic agent, requires metabolic activation through a mixed-function oxygenase system. The capacity of this agent to produce oncogenic transformation and chromosomal damage, including increases in sister chromatid exchanges, was investigated in cell culture with or without an exogenous liver metabolic activation system. No oncogenic transformation or chromosomal aberrations were produced by cyclophosphamide in the absence of metabolic activation, whereas significant transformation, chromosomal breaks, and increases in sister chromatid exchanges were observed when the activation system was incorporated into the assays. The oncogenic transformation and chromosomal changes were completely eliminated by removing glucose 6-phosphate and nicotinamide adenine dinucleotide phosphate from the metabolic generating system. These studies emphasize the necessity to incorporate some activation procedure into short-term assays used for evaluating the mutagenic and/or oncogenic potential of various chemicals."}
{"id": "PMID:28181", "title": "Complexes of trivalent oxygenated phosphorus compounds with cytochrome P-450 and cytochrome P-420: the origin of double Soret spectra.", "content": "Trivalent oxygenated phosphorus ligands include alkyl and aryl phosphites, (RO)3P, phosphonites, (RO)2PR, and phosphinites, ROPR2. All such compounds tested, with the exception of triphenyl phosphite, interact with ferrous cytochrome P-450 and its denatured form, cytochrome P-420, to produce complexes having two peaks in the Soret region of their optical difference spectra. Careful evaluation of these spectra indicate that they arise for different reasons for each of the two cytochromes. Clear evidence shows that cytochrome P-450 is not denatured by these ligands. The high affinity of these ligands for heme iron is indicated by small Ks values. The experimental results are used to substantiate a theory of the origin of microsomal double Soret spectra and the nature of the environments available for microsomal cytochromes P-450 and P-420.", "contents": "Complexes of trivalent oxygenated phosphorus compounds with cytochrome P-450 and cytochrome P-420: the origin of double Soret spectra. Trivalent oxygenated phosphorus ligands include alkyl and aryl phosphites, (RO)3P, phosphonites, (RO)2PR, and phosphinites, ROPR2. All such compounds tested, with the exception of triphenyl phosphite, interact with ferrous cytochrome P-450 and its denatured form, cytochrome P-420, to produce complexes having two peaks in the Soret region of their optical difference spectra. Careful evaluation of these spectra indicate that they arise for different reasons for each of the two cytochromes. Clear evidence shows that cytochrome P-450 is not denatured by these ligands. The high affinity of these ligands for heme iron is indicated by small Ks values. The experimental results are used to substantiate a theory of the origin of microsomal double Soret spectra and the nature of the environments available for microsomal cytochromes P-450 and P-420."}
{"id": "PMID:28182", "title": "The anaerobic dechlorination of trichlorofluoromethane by rat liver preparations in vitro.", "content": "Incubation of trichlorofluoromethane with a liver microsomal fraction and an NADPH generating system under anaerobic conditions produced a metabolite dichlorofluoromethane, characterised by gas chromatography and mass spectrometry. The metabolic reaction was carried out by liver microsomes from the mouse, rabbit, hamster and rat and was increased by phenobarbitone pre-treatment. The formation of dichlorofluoromethane in vitro was enhanced by the addition of FMN, but partially inhibited by the presence of air, oxygen, SK&F 525-A, metyrapone and carbon tetrachloride and totally inhibited by carbon monoxide. The consumption of NADPH in the reaction was greater than could be accounted for by the production of dichlorofluoromethane indicating the possible formation of other metabolic products. It is suggested that trichlorofluoromethane interacts with the reduced form of cytochrome P-450 at the oxygen binding site and a possible mechanism for its subsequent reductive dechlorination is proposed.", "contents": "The anaerobic dechlorination of trichlorofluoromethane by rat liver preparations in vitro. Incubation of trichlorofluoromethane with a liver microsomal fraction and an NADPH generating system under anaerobic conditions produced a metabolite dichlorofluoromethane, characterised by gas chromatography and mass spectrometry. The metabolic reaction was carried out by liver microsomes from the mouse, rabbit, hamster and rat and was increased by phenobarbitone pre-treatment. The formation of dichlorofluoromethane in vitro was enhanced by the addition of FMN, but partially inhibited by the presence of air, oxygen, SK&F 525-A, metyrapone and carbon tetrachloride and totally inhibited by carbon monoxide. The consumption of NADPH in the reaction was greater than could be accounted for by the production of dichlorofluoromethane indicating the possible formation of other metabolic products. It is suggested that trichlorofluoromethane interacts with the reduced form of cytochrome P-450 at the oxygen binding site and a possible mechanism for its subsequent reductive dechlorination is proposed."}
{"id": "PMID:28184", "title": "A comparison of the effects of 5- and 6-hydroxydopamine on the isolated canine saphenous vein.", "content": "We studied and compared the effects of 5- and 6-hydroxydopamine (5- or 6-OHDA) on venous tone and on adrenergic and nonadrenergic responses of the isolated canine saphenous vein. In the tissue bath, both 5- and 6-OHDA caused increases in tone and abolished adrenergic responses to transmural nerve stimulation. Effects of 6-OHDA were blocked by desmethylimipramine. 6-OHDA reduced norepinephrine levels of venous strips to 15% of those in control strips. Neither 5- nor 6-OHDA markedly altered peak contractile responses to norepinephrine but 6-OHDA prolonged the response to norepinephrine. Both compounds reduced responses to tyramine, with 6-OHDA producing a greater reduction than 5-OHDA. Large contractile responses to 5-OHDA were blocked only partially by treatment of strips with 6-OHDA, suggesting that contractile responses to 5-OHDA were mediated by direct and indirect actions. These results suggest differences in the actions of 5- and 6-OHDA on adrenergic terminals and smooth muscle in saphenous veins. The results of the experiments suggest that both 5- and 6-OHDA may be useful pharmacological interventions for the study of adrenergic mechanisms in isolated blood vessels.", "contents": "A comparison of the effects of 5- and 6-hydroxydopamine on the isolated canine saphenous vein. We studied and compared the effects of 5- and 6-hydroxydopamine (5- or 6-OHDA) on venous tone and on adrenergic and nonadrenergic responses of the isolated canine saphenous vein. In the tissue bath, both 5- and 6-OHDA caused increases in tone and abolished adrenergic responses to transmural nerve stimulation. Effects of 6-OHDA were blocked by desmethylimipramine. 6-OHDA reduced norepinephrine levels of venous strips to 15% of those in control strips. Neither 5- nor 6-OHDA markedly altered peak contractile responses to norepinephrine but 6-OHDA prolonged the response to norepinephrine. Both compounds reduced responses to tyramine, with 6-OHDA producing a greater reduction than 5-OHDA. Large contractile responses to 5-OHDA were blocked only partially by treatment of strips with 6-OHDA, suggesting that contractile responses to 5-OHDA were mediated by direct and indirect actions. These results suggest differences in the actions of 5- and 6-OHDA on adrenergic terminals and smooth muscle in saphenous veins. The results of the experiments suggest that both 5- and 6-OHDA may be useful pharmacological interventions for the study of adrenergic mechanisms in isolated blood vessels."}
{"id": "PMID:28185", "title": "Separation and analysis of arylsulfatase isoenzymes in body fluids of man.", "content": "Soluble arylsulfatase (EC 3.1.6.1) is present in the body fluids of man in the form of two isoenzymes, arylsulfatase A and B, which reportedly are useful biochemical markers for certain types of malignancy. However, rapid assay of the individual isoenzymes is extremely difficult; procedures based on differential inhibition or activation of the isoenzymes in a mixture yield only semiquantitative results. A feature of these isoenzymes is their inhibition by some common anions (notably phosphate) at physiologic concentrations. The isoenzymes can be separated by anion-exchange chromatography, the B isoenzyme being eluted in the void volume and the A isoenzyme and the anionic inhibitors retarded. Lead is used to sequester phosphate, enabling measurement of A in the salt-eluted fraction. Using this technique, we have found significant elevations of B in the sera of patients with colorectal cancer. The potential of rapid, chromatographic separation coupled with continuous monitoring for arylsulfatase activity is discussed.", "contents": "Separation and analysis of arylsulfatase isoenzymes in body fluids of man. Soluble arylsulfatase (EC 3.1.6.1) is present in the body fluids of man in the form of two isoenzymes, arylsulfatase A and B, which reportedly are useful biochemical markers for certain types of malignancy. However, rapid assay of the individual isoenzymes is extremely difficult; procedures based on differential inhibition or activation of the isoenzymes in a mixture yield only semiquantitative results. A feature of these isoenzymes is their inhibition by some common anions (notably phosphate) at physiologic concentrations. The isoenzymes can be separated by anion-exchange chromatography, the B isoenzyme being eluted in the void volume and the A isoenzyme and the anionic inhibitors retarded. Lead is used to sequester phosphate, enabling measurement of A in the salt-eluted fraction. Using this technique, we have found significant elevations of B in the sera of patients with colorectal cancer. The potential of rapid, chromatographic separation coupled with continuous monitoring for arylsulfatase activity is discussed."}
{"id": "PMID:28186", "title": "Acid beta-glucosidase and the diagnosis of Gaucher's disease in liver and spleen.", "content": "Variable amounts of residual 4-methylumbelliferyl-beta-glucosidase activity gave rise to difficulties in the diagnosis of Gaucher's disease using spleen and particularly liver. Soluble and particulate components of beta-glucosidase, which interfere with the diagnosis, may be eliminated by preincubation of homogenates at pH 3.0 or with 100 mM sodium chloride at pH 4.0. After either of these treatments the optimum of acid beta-glucosidase was pH 4.5 and diagnosis of Gaucher's disease could be more easily made using homogenates of spleen and liver. There was residual acid beta-glucosidase activity in one of the Gaucher livers.", "contents": "Acid beta-glucosidase and the diagnosis of Gaucher's disease in liver and spleen. Variable amounts of residual 4-methylumbelliferyl-beta-glucosidase activity gave rise to difficulties in the diagnosis of Gaucher's disease using spleen and particularly liver. Soluble and particulate components of beta-glucosidase, which interfere with the diagnosis, may be eliminated by preincubation of homogenates at pH 3.0 or with 100 mM sodium chloride at pH 4.0. After either of these treatments the optimum of acid beta-glucosidase was pH 4.5 and diagnosis of Gaucher's disease could be more easily made using homogenates of spleen and liver. There was residual acid beta-glucosidase activity in one of the Gaucher livers."}
{"id": "PMID:28187", "title": "Methylmalonic/beta-hydroxy-n-valeric aciduria due to methylmalonyl-CoA mutase deficiency.", "content": "A patient with methylmalonic and beta-hydroxy-n-valeric aciduria, apparently due to deficiency of methylmalonyl-CoA mutase, is described. The excretion of beta-hydroxy-n-valerate did not parallel that of beta-hydroxypropionate and methylmalonate but was observed, together with beta-keto-n-valerate, only during ketosis. beta-Hydroxy-n-valerate excretion thus correlates primarily not with the pool size of propionyl-CoA but with that of acetyl-CoA, and may occur during ketosis in any disorder causing accumulation of propionyl-CoA.", "contents": "Methylmalonic/beta-hydroxy-n-valeric aciduria due to methylmalonyl-CoA mutase deficiency. A patient with methylmalonic and beta-hydroxy-n-valeric aciduria, apparently due to deficiency of methylmalonyl-CoA mutase, is described. The excretion of beta-hydroxy-n-valerate did not parallel that of beta-hydroxypropionate and methylmalonate but was observed, together with beta-keto-n-valerate, only during ketosis. beta-Hydroxy-n-valerate excretion thus correlates primarily not with the pool size of propionyl-CoA but with that of acetyl-CoA, and may occur during ketosis in any disorder causing accumulation of propionyl-CoA."}
{"id": "PMID:28188", "title": "Glycogenosis type II: the infantile- and late-onset acid maltase deficiency observed in one family.", "content": "The concurrence of the infantile and adult form of acid maltase deficiency in one family is presented. The muscle of both cases possesses residual activity. The glycogen amount in the infantile form is increased tremendously, while in the late-onset the amount of glycogen is normal.", "contents": "Glycogenosis type II: the infantile- and late-onset acid maltase deficiency observed in one family. The concurrence of the infantile and adult form of acid maltase deficiency in one family is presented. The muscle of both cases possesses residual activity. The glycogen amount in the infantile form is increased tremendously, while in the late-onset the amount of glycogen is normal."}
{"id": "PMID:28189", "title": "Considerations on physiopathological approaches to the treatment of hypertension.", "content": "1. Two main physiopathological approaches to the treatment of hypertension are discussed, the first based on renin profiling and the second on haemodynamic measurements. 2. Reduction in plasma renin activity does not appear to be a clinically important mechanism in the hypotensive effect of beta-adrenergic blockers and of alpha-methyldopa. In particular, alpha-methyldopa has been found equally effective as a hypotensive agent both in normal renin and in low renin hypertensive patients. 3. Diuretics are certainly possessed of a renin-stimulating action, but in most patients this action does not obscure the hypotensive effect of these drugs. 4. Responders and non-responders to the hypotensive activity of beta-adrenergic blockers do not differ among them in their control haemodynamics.", "contents": "Considerations on physiopathological approaches to the treatment of hypertension. 1. Two main physiopathological approaches to the treatment of hypertension are discussed, the first based on renin profiling and the second on haemodynamic measurements. 2. Reduction in plasma renin activity does not appear to be a clinically important mechanism in the hypotensive effect of beta-adrenergic blockers and of alpha-methyldopa. In particular, alpha-methyldopa has been found equally effective as a hypotensive agent both in normal renin and in low renin hypertensive patients. 3. Diuretics are certainly possessed of a renin-stimulating action, but in most patients this action does not obscure the hypotensive effect of these drugs. 4. Responders and non-responders to the hypotensive activity of beta-adrenergic blockers do not differ among them in their control haemodynamics."}
{"id": "PMID:28190", "title": "alpha-Methyldopa and beta-blockers in hypertension--a comparison of their haemodynamic effects.", "content": "1. During acute injection of alpha-methyldopa there is a reduction in the blood pressure within a period of a few hours and a modest reduction in the cardiac output, sometimes due to a modest decrease in heart rate. Frequently the total peripheral resistance is decreased. In contrast, acute injection of beta-blockers induces a marked decrease in heart rate and cardiac output, a compensatory increase in the total peripheral resistance and no decrease in the blood pressure. 2. During long-term use alpha-methyldopa frequently reduces the total peripheral resistance and the reduction in cardiac output is usually modest, at rest as well as during exercise. The beta-blockers reduce the blood pressure, but induce a marked decrease in cardiac output and heart rate. The total peripheral resistance is little affected compared to the pre-treatment level.", "contents": "alpha-Methyldopa and beta-blockers in hypertension--a comparison of their haemodynamic effects. 1. During acute injection of alpha-methyldopa there is a reduction in the blood pressure within a period of a few hours and a modest reduction in the cardiac output, sometimes due to a modest decrease in heart rate. Frequently the total peripheral resistance is decreased. In contrast, acute injection of beta-blockers induces a marked decrease in heart rate and cardiac output, a compensatory increase in the total peripheral resistance and no decrease in the blood pressure. 2. During long-term use alpha-methyldopa frequently reduces the total peripheral resistance and the reduction in cardiac output is usually modest, at rest as well as during exercise. The beta-blockers reduce the blood pressure, but induce a marked decrease in cardiac output and heart rate. The total peripheral resistance is little affected compared to the pre-treatment level."}
{"id": "PMID:28191", "title": "Immunotherapy of human acute leukaemia.", "content": "Conclusions are difficult to draw. In the six studies of immunotherapy of AML discussed, all the three employing BCG and cells showed a prolongation of survival and the major contributing factor to this prolongation of survival was extension of life after relapse. In the three studies using BCG alone only one shows a beneficial effect, but some more time must be allowed to elapse before this can be concluded with confidence.", "contents": "Immunotherapy of human acute leukaemia. Conclusions are difficult to draw. In the six studies of immunotherapy of AML discussed, all the three employing BCG and cells showed a prolongation of survival and the major contributing factor to this prolongation of survival was extension of life after relapse. In the three studies using BCG alone only one shows a beneficial effect, but some more time must be allowed to elapse before this can be concluded with confidence."}
{"id": "PMID:28193", "title": "Pamatolol: phase I evaluation of the pharmacodynamics of a cardioselective beta adrenoceptor blocking drug.", "content": "A Phase I evaluation of a new adrenoceptor blocker, pamatolol, was performed in 10 healthy male volunteers. Minor reductions in standing and exercise and isoproterenol-induced increases in heart rate were observed with the 10-mg oral dose and appeared maximal with the 400-600 mg dose. The rate of decline of effect averaged 1.5% of the exercise heart rate/hr. Neither resting systolic time intervals nor post-exercise pulmonary function was affected by this dose range of pamatolol. Based on the latter responses and the isoproterenol dose response curve, we tentatively conclude that pamatolol is relatively cardioselective in man.", "contents": "Pamatolol: phase I evaluation of the pharmacodynamics of a cardioselective beta adrenoceptor blocking drug. A Phase I evaluation of a new adrenoceptor blocker, pamatolol, was performed in 10 healthy male volunteers. Minor reductions in standing and exercise and isoproterenol-induced increases in heart rate were observed with the 10-mg oral dose and appeared maximal with the 400-600 mg dose. The rate of decline of effect averaged 1.5% of the exercise heart rate/hr. Neither resting systolic time intervals nor post-exercise pulmonary function was affected by this dose range of pamatolol. Based on the latter responses and the isoproterenol dose response curve, we tentatively conclude that pamatolol is relatively cardioselective in man."}
{"id": "PMID:28194", "title": "Assessing the subjective effects of stimulants in casual users. A methodology and preliminary results.", "content": "In order to assess the subjective effects of nefopam, a new non-opiate analgesic, a study was designed using highly educated, young, middle-to-upper class subjects in a naturalistic setting. Results suggest that the design is capable of differentiating variations in subjective drug effects. On a number of measures, 10 mg of d-amphetamine, a modest dosage, could be distinguished from placebo, showing changes in the direction expected for stimulant drugs. Nefopam (90 mg), on the other hand, showed few differences from placebo or caffeine (300 mg). Nefopam appeared mildly dysphoric, rather than stimulant, in subjective effects.", "contents": "Assessing the subjective effects of stimulants in casual users. A methodology and preliminary results. In order to assess the subjective effects of nefopam, a new non-opiate analgesic, a study was designed using highly educated, young, middle-to-upper class subjects in a naturalistic setting. Results suggest that the design is capable of differentiating variations in subjective drug effects. On a number of measures, 10 mg of d-amphetamine, a modest dosage, could be distinguished from placebo, showing changes in the direction expected for stimulant drugs. Nefopam (90 mg), on the other hand, showed few differences from placebo or caffeine (300 mg). Nefopam appeared mildly dysphoric, rather than stimulant, in subjective effects."}
{"id": "PMID:28195", "title": "Analytical subcellular fractionation studies on enterocytes from the jejunum and ileum of the rat and some properties of brush-border alkaline phosphatase.", "content": "1. Enterocytes, isolated from the proximal jejinum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per entercocyte. 2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). The values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes. 3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell. 4. Isolated jejunal brush-border preprations showed latent activities of both alkaline phosphatase and gamma-glutamyltransferase whereas the activities of alpha-glucosidase and leucyl-beta-naphylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility.", "contents": "Analytical subcellular fractionation studies on enterocytes from the jejunum and ileum of the rat and some properties of brush-border alkaline phosphatase. 1. Enterocytes, isolated from the proximal jejinum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per entercocyte. 2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). The values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes. 3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell. 4. Isolated jejunal brush-border preprations showed latent activities of both alkaline phosphatase and gamma-glutamyltransferase whereas the activities of alpha-glucosidase and leucyl-beta-naphylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility."}
{"id": "PMID:28196", "title": "Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion.", "content": "1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion.", "contents": "Urinary dopamine in man and rat: effects of inorganic salts on dopamine excretion. 1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion."}
{"id": "PMID:28197", "title": "Effect of varying PCO2 on intracellular pH and lactate consumption in the isolated perfused rat liver.", "content": "1. The effects of varying PCO2 on lactate uptake and intracellular pH (pHi) were studied in the isolated rat liver perfused with differing concentration of lactate. 2. In general, pHi and lactate uptake are inversely related to PCO2, and pHi and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation. 3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues. 4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure.", "contents": "Effect of varying PCO2 on intracellular pH and lactate consumption in the isolated perfused rat liver. 1. The effects of varying PCO2 on lactate uptake and intracellular pH (pHi) were studied in the isolated rat liver perfused with differing concentration of lactate. 2. In general, pHi and lactate uptake are inversely related to PCO2, and pHi and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation. 3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues. 4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure."}
{"id": "PMID:28198", "title": "Mechanism of the effect of varying PCO2 on gluconeogenesis from lactate in the perfused rat liver.", "content": "1. The effects of varying PCO2 on glucose output and the intracellular concentrations of lactate, pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate were studied in the isolated rat liver perfused with differing concentrations of lactate. 2. When the perfusate lactate concentration is above 1.5 mmol/l respiratory acidosis (simulated by high perfusate PCO2) inhibits gluconeogenesis from lactate, whereas respiratory alkalosis stimulates gluconeogenesis. 3. In general there were significant positive correlations between intracellular pH (pHi) and hepatocyte phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate concentrations, and negative correlations between pHi and lactate and pyruvate concentrations; there were usually significant correlations in the opposite  sense between these metabolites and log PCO2. 4. The results suggest that CO2 exerts an inhibitory effect on gluconeogenesis at a step between pyruvate and phosphoenolypruvate; however, this is not the only effect of CO2 on the gluconeogenic sequence. CO2 probably acts by changing pHi, but direct effects of CO2 and HCO-3 cannot be excluded. 5. Except at low lactate concentrations, nonionic diffusion probably does not play a major role in the entry of lactate into the hepatocyte.", "contents": "Mechanism of the effect of varying PCO2 on gluconeogenesis from lactate in the perfused rat liver. 1. The effects of varying PCO2 on glucose output and the intracellular concentrations of lactate, pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate were studied in the isolated rat liver perfused with differing concentrations of lactate. 2. When the perfusate lactate concentration is above 1.5 mmol/l respiratory acidosis (simulated by high perfusate PCO2) inhibits gluconeogenesis from lactate, whereas respiratory alkalosis stimulates gluconeogenesis. 3. In general there were significant positive correlations between intracellular pH (pHi) and hepatocyte phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate concentrations, and negative correlations between pHi and lactate and pyruvate concentrations; there were usually significant correlations in the opposite  sense between these metabolites and log PCO2. 4. The results suggest that CO2 exerts an inhibitory effect on gluconeogenesis at a step between pyruvate and phosphoenolypruvate; however, this is not the only effect of CO2 on the gluconeogenic sequence. CO2 probably acts by changing pHi, but direct effects of CO2 and HCO-3 cannot be excluded. 5. Except at low lactate concentrations, nonionic diffusion probably does not play a major role in the entry of lactate into the hepatocyte."}
{"id": "PMID:28219", "title": "[Crohn's disease: course and prognosis in 169 patients (author's transl)].", "content": "The most common initial symptoms in 169 patients with Crohn's disease, followed from 1956 to 1973, were diffuse abdominal pain, diarrhoea without any blood admixture, loss of weight, and fever. At the onset of the disease 84% of patients were aged 10-39 years. The most important complications (in descending order of frequency) were fistulae and abscesses, ileus, anaemia, and malabsorption. A breakdown into active and passive phases indicated that the younger the patient at onset of the disease, the more severe its course. The disease seemed to take a more favourable course when only the colon, but not the terminal ileum, was involved. Recurrence occurred more frequently after a short than after a long preoperative history. Recurrences were more frequent in patients under than over 31 years of age at their first operation.", "contents": "[Crohn's disease: course and prognosis in 169 patients (author's transl)]. The most common initial symptoms in 169 patients with Crohn's disease, followed from 1956 to 1973, were diffuse abdominal pain, diarrhoea without any blood admixture, loss of weight, and fever. At the onset of the disease 84% of patients were aged 10-39 years. The most important complications (in descending order of frequency) were fistulae and abscesses, ileus, anaemia, and malabsorption. A breakdown into active and passive phases indicated that the younger the patient at onset of the disease, the more severe its course. The disease seemed to take a more favourable course when only the colon, but not the terminal ileum, was involved. Recurrence occurred more frequently after a short than after a long preoperative history. Recurrences were more frequent in patients under than over 31 years of age at their first operation."}
{"id": "PMID:28220", "title": "Studies on the microsomal metabolism and binding of polybrominated biphenyls (PBBs).", "content": "The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric O2. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of only peaks 1 (2,4,5,2',5'-pentabromobiphenyl) and 3 (a hexabromobiphenyl) were observed following incubations with microsomes from phenobarbital (PB)- or PBBS- pretreated rats. Of seven structurally identified PBB components, only peak 1 has a bromine-free para position. Peaks 1, 2, and 5 all have two adjacent unsubstituted carbons, yet only peak 1 is metabolized. Of two dibromobiphenyl model compounds studied, the 2,2'-congener was very rapidly metabolized by PB-induced microsomes whereas its 4,4'-isomer was not. These results suggest that the presence of a free para position is required for the metabolism of brominated biphenyls. Of lesser importance appears to be the number of bromines or the availability of two adjacent unsubstituted carbons. In vivo evidence for the metabolism of peaks 1 and 3 was also provided by their drastically diminished levels in liver and milk extracts. When a 14C-PBB mixture consisting almost exclusively of peaks 4 (2,4,5,2',4',5'-hexabromobiphenyl) and 8 (2,3,4,5,2',4',5'-heptabromobiphenyl) was incubated with PB- or PBBs- induced microsomes and NADPH, only traces of radioactivity remained with the microsomes after extensive extraction. However, less radioactivity was bound to microsomes from MC pretreated or especially control rats. No radioactivity was bound to exogenous DNA included in similar microsomal incubations, regardless of the type of microsomes used. Under the same conditions, [3H]-benzo[a]pyrene metabolites were bound to DNA, and PBB-induced microsomes enhanced this binding more than six-fold.", "contents": "Studies on the microsomal metabolism and binding of polybrominated biphenyls (PBBs). The metabolism of polybrominated biphenyls (PBBs) was studied in vitro by using rat liver microsomes in the presence of NADPH and atmospheric O2. Quantitative recoveries of all PBBs were obtained after incubations with control or 3-methylcholanthrene (MC) induced microsomes. Of the twelve major components, losses of only peaks 1 (2,4,5,2',5'-pentabromobiphenyl) and 3 (a hexabromobiphenyl) were observed following incubations with microsomes from phenobarbital (PB)- or PBBS- pretreated rats. Of seven structurally identified PBB components, only peak 1 has a bromine-free para position. Peaks 1, 2, and 5 all have two adjacent unsubstituted carbons, yet only peak 1 is metabolized. Of two dibromobiphenyl model compounds studied, the 2,2'-congener was very rapidly metabolized by PB-induced microsomes whereas its 4,4'-isomer was not. These results suggest that the presence of a free para position is required for the metabolism of brominated biphenyls. Of lesser importance appears to be the number of bromines or the availability of two adjacent unsubstituted carbons. In vivo evidence for the metabolism of peaks 1 and 3 was also provided by their drastically diminished levels in liver and milk extracts. When a 14C-PBB mixture consisting almost exclusively of peaks 4 (2,4,5,2',4',5'-hexabromobiphenyl) and 8 (2,3,4,5,2',4',5'-heptabromobiphenyl) was incubated with PB- or PBBs- induced microsomes and NADPH, only traces of radioactivity remained with the microsomes after extensive extraction. However, less radioactivity was bound to microsomes from MC pretreated or especially control rats. No radioactivity was bound to exogenous DNA included in similar microsomal incubations, regardless of the type of microsomes used. Under the same conditions, [3H]-benzo[a]pyrene metabolites were bound to DNA, and PBB-induced microsomes enhanced this binding more than six-fold."}
{"id": "PMID:28225", "title": "Purification and properties of 5'-nucleotidase from lymphocyte plasma membranes.", "content": "5'-Nucleotidase is purified from lymphocyte plasma membranes by two affinity chromatographies. The first one, on Lens culinaris lectin-Sepharose 4B yields a fraction of twelve lectin-binding glycoproteins (lectin-receptor fraction). The second one on 5'-AMP-Sepharose 4B leads to pure enzyme. This enzyme is a glycoprotein with a molecular weight of 130 000; it gives a single band in polyacrylamide/dodecylsulfate electrophoresis and displays a very high specific activity (2500-3000 mumol Pih-1mg-1). Some properties of purified 5'-nucleotidase are similar to those of membrane-bound enzyme: substrate specificity, temperature dependence, effects of ions and SH-blocking reagents. Others are completely different for the two systems and these differences result from an interaction between the enzyme molecule and other Lens culinaris lectin binding proteins.", "contents": "Purification and properties of 5'-nucleotidase from lymphocyte plasma membranes. 5'-Nucleotidase is purified from lymphocyte plasma membranes by two affinity chromatographies. The first one, on Lens culinaris lectin-Sepharose 4B yields a fraction of twelve lectin-binding glycoproteins (lectin-receptor fraction). The second one on 5'-AMP-Sepharose 4B leads to pure enzyme. This enzyme is a glycoprotein with a molecular weight of 130 000; it gives a single band in polyacrylamide/dodecylsulfate electrophoresis and displays a very high specific activity (2500-3000 mumol Pih-1mg-1). Some properties of purified 5'-nucleotidase are similar to those of membrane-bound enzyme: substrate specificity, temperature dependence, effects of ions and SH-blocking reagents. Others are completely different for the two systems and these differences result from an interaction between the enzyme molecule and other Lens culinaris lectin binding proteins."}
{"id": "PMID:28227", "title": "Purification of aspartate transcarbamylase from Drosophila melanogaster.", "content": "A purification procedure is described by which aspartate transcarbamylase was obtained from cultured cells of Drosophila melanogaster as part of a high-molecular-weight enzyme complex. The complex is shown to contain several polypeptides. An antiserum directed against the complex enzyme inhibited in vitro the activity of aspartate transcarbamylase, carbamylphosphate synthetase and dihydro-orotase which were shown to copurify on a sucrose gradient and by gel electrophoresis. A fast preparation procedure using this antiserum yielded a 220 000-molecular-weight protein in addition to the polypeptides present in the complex. A purification procedure is also described to obtain aspartate transcarbamylase from second instar larvae of Drosophila. At this stage, the enzyme is not complexed with carbamylphosphate synthetase and dihydro-orotase but exhibits the same molecular weight as the aspartate transcarbamylase moiety found in the high-molecular-weight complex of cultured cells.", "contents": "Purification of aspartate transcarbamylase from Drosophila melanogaster. A purification procedure is described by which aspartate transcarbamylase was obtained from cultured cells of Drosophila melanogaster as part of a high-molecular-weight enzyme complex. The complex is shown to contain several polypeptides. An antiserum directed against the complex enzyme inhibited in vitro the activity of aspartate transcarbamylase, carbamylphosphate synthetase and dihydro-orotase which were shown to copurify on a sucrose gradient and by gel electrophoresis. A fast preparation procedure using this antiserum yielded a 220 000-molecular-weight protein in addition to the polypeptides present in the complex. A purification procedure is also described to obtain aspartate transcarbamylase from second instar larvae of Drosophila. At this stage, the enzyme is not complexed with carbamylphosphate synthetase and dihydro-orotase but exhibits the same molecular weight as the aspartate transcarbamylase moiety found in the high-molecular-weight complex of cultured cells."}
{"id": "PMID:28228", "title": "Identification of the functional ionic groups of papain by pH/rate profile analysis.", "content": "The pH dependence of papain catalysis was analyzed by a scheme which evaluates the kinetic contribution of both protonated and unprotonated species of functional groups involved in catalysis. Kinetic measurements were made at constant pH, without buffers, by automatic titration. The rate-determining step for papain-catalyzed hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester, determined by nucleophile competition, changed from acylation below pH 6.5 to mixed acylation-deacylation above pH 6.5. Kinetic analysis indicated that three prototropic groups governed the pH-specificity of alpha-N-benzoyl-L-arginine ethyl ester hydrolysis. These prototropic groups had pKa values of 4.8, 6.5 to 6.7, and 8.7. Theoretical treatment of the kinetics provided an excellent fit with the experimentally found profile when the contribution of all three prototropic groups was considered. Analysis showed that, in acid, the pathways of papain catalysis were functional with either two or three active-site protons. In base, a single functional ionic pathway is associated with an active site with only one proton. Pathways involving an unprotonated active site are catalytically inoperative in both acid and base. These results indicate that papain exhibits several catalytically functional ionic pathways. The results are discussed in terms of pKa assignments, and the mechanism of papain catalysis.", "contents": "Identification of the functional ionic groups of papain by pH/rate profile analysis. The pH dependence of papain catalysis was analyzed by a scheme which evaluates the kinetic contribution of both protonated and unprotonated species of functional groups involved in catalysis. Kinetic measurements were made at constant pH, without buffers, by automatic titration. The rate-determining step for papain-catalyzed hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester, determined by nucleophile competition, changed from acylation below pH 6.5 to mixed acylation-deacylation above pH 6.5. Kinetic analysis indicated that three prototropic groups governed the pH-specificity of alpha-N-benzoyl-L-arginine ethyl ester hydrolysis. These prototropic groups had pKa values of 4.8, 6.5 to 6.7, and 8.7. Theoretical treatment of the kinetics provided an excellent fit with the experimentally found profile when the contribution of all three prototropic groups was considered. Analysis showed that, in acid, the pathways of papain catalysis were functional with either two or three active-site protons. In base, a single functional ionic pathway is associated with an active site with only one proton. Pathways involving an unprotonated active site are catalytically inoperative in both acid and base. These results indicate that papain exhibits several catalytically functional ionic pathways. The results are discussed in terms of pKa assignments, and the mechanism of papain catalysis."}
{"id": "PMID:28230", "title": "Hyperphenylalaninaemia due to dihydropteridine reductase deficiency.", "content": "Two siblings with increased levels of serum phenylalanine were detected by newborn screening. The older sibling deteriorated neurologically and mentally, despite early dietary control, and died at the age of 6 1/2 years. In the younger sibling phenylalanine hydroxylase activity in liver tissue was normal. Further investigations revealed increased concentrations of biopterin derivatives in the blood, a low excretion of 5-hydroxyindole acetic acid in the urine, and a dihydropteridine reductase deficiency as the cause of hyperphenylalaninaemia. The parents of the siblings showed 50% of the normal dihydropteridine reductase activity in their fibroblasts grown in culture. Neurotransmitter therapy was started in the second child at the age of 6 months and this was followed by distinct neurological and mental improvement.", "contents": "Hyperphenylalaninaemia due to dihydropteridine reductase deficiency. Two siblings with increased levels of serum phenylalanine were detected by newborn screening. The older sibling deteriorated neurologically and mentally, despite early dietary control, and died at the age of 6 1/2 years. In the younger sibling phenylalanine hydroxylase activity in liver tissue was normal. Further investigations revealed increased concentrations of biopterin derivatives in the blood, a low excretion of 5-hydroxyindole acetic acid in the urine, and a dihydropteridine reductase deficiency as the cause of hyperphenylalaninaemia. The parents of the siblings showed 50% of the normal dihydropteridine reductase activity in their fibroblasts grown in culture. Neurotransmitter therapy was started in the second child at the age of 6 months and this was followed by distinct neurological and mental improvement."}
{"id": "PMID:28231", "title": "Effects of stored and fresh blood transfusions on postoperative pulmonary function. A clinical study on patients following extracorporeal circulation in association with aortic valve surgery.", "content": "The effects on postoperative pulmonary function of fresh versus stored blood when priming the heart-lung machine were studied in 49 patients subjected to aortic valvular replacement. The onset of extracorporeal circulation was considered to mimic the conditions of massive blood transfusion. The patients receiving heparinized fresh blood required more oxygen in the respirator than those receiving stored blood, but still had a significantly lower arterial oxygen tension during the first and second postoperative days. The fresh blood patients also showed a tendency to require a larger amount of diuretics to maintain adequate urine output. Pre- and postoperative bleeding and changes in postoperative hematological variables did not differ in the two groups. The results imply that stored blood should be preferable when substituting blood losses.", "contents": "Effects of stored and fresh blood transfusions on postoperative pulmonary function. A clinical study on patients following extracorporeal circulation in association with aortic valve surgery. The effects on postoperative pulmonary function of fresh versus stored blood when priming the heart-lung machine were studied in 49 patients subjected to aortic valvular replacement. The onset of extracorporeal circulation was considered to mimic the conditions of massive blood transfusion. The patients receiving heparinized fresh blood required more oxygen in the respirator than those receiving stored blood, but still had a significantly lower arterial oxygen tension during the first and second postoperative days. The fresh blood patients also showed a tendency to require a larger amount of diuretics to maintain adequate urine output. Pre- and postoperative bleeding and changes in postoperative hematological variables did not differ in the two groups. The results imply that stored blood should be preferable when substituting blood losses."}
{"id": "PMID:28232", "title": "Hemodynamic and metabolic changes induced by temporary clamping of the thoracic aorta.", "content": "Numerous authors reported a significant deterioration of heart function induced by aortic cross-clamping. Nevertheless, the aorta has been clamped during various surgical procedures without any complication. We studied the hemodynamic and metabolic variations induced by 20 min thoracic aorta cross-clamping in 6 open-chest dogs. During clamping the most striking modifications were an increase in coronary blood flow of over 65%, an increase in cardiac work of over 77% and an increase in total peripheral resistances of over 68% compared to base values. No significant variations were found in the heart rate and cardiac index. Metabolic parameters, such as O2 consumption and lactate consumption increased significantly during the clamping period. The increase in lactate consumption and the progressive and continuous improvement in oxygenation indexes (lactate/pyruvate, redox potential, excess of lactate) proved the absence of any myocardial anoxia during this period. Within 15--30 min after declamping all hemodynamic and metabolic parameters reverted to values close to basal values. These data strongly suggest that the mammalian heart can tolerate this procedure satisfactorily for a limited period of time. In clinical settings, one should consider the base conditions of the cardiovascular system before transposing these conclusions.", "contents": "Hemodynamic and metabolic changes induced by temporary clamping of the thoracic aorta. Numerous authors reported a significant deterioration of heart function induced by aortic cross-clamping. Nevertheless, the aorta has been clamped during various surgical procedures without any complication. We studied the hemodynamic and metabolic variations induced by 20 min thoracic aorta cross-clamping in 6 open-chest dogs. During clamping the most striking modifications were an increase in coronary blood flow of over 65%, an increase in cardiac work of over 77% and an increase in total peripheral resistances of over 68% compared to base values. No significant variations were found in the heart rate and cardiac index. Metabolic parameters, such as O2 consumption and lactate consumption increased significantly during the clamping period. The increase in lactate consumption and the progressive and continuous improvement in oxygenation indexes (lactate/pyruvate, redox potential, excess of lactate) proved the absence of any myocardial anoxia during this period. Within 15--30 min after declamping all hemodynamic and metabolic parameters reverted to values close to basal values. These data strongly suggest that the mammalian heart can tolerate this procedure satisfactorily for a limited period of time. In clinical settings, one should consider the base conditions of the cardiovascular system before transposing these conclusions."}
{"id": "PMID:28233", "title": "Climbing behaviour induced by apomorphine in mice: a potential model for the detection of neuroleptic activity.", "content": "Apomorphine and the putative dopamine agonist, 2-(N, N-dipropyl)-amino-5, 6-dihydroxytetralin induced dose-dependent climbing behaviour in the mouse which was measured in wire mesh lined cages as the percentage of time spent climbing in the 30 min period following the first climb and as the maximum time spent in a single climb throughout the drug effect. These These two measures were generally found to parallel excepting when the interacting agent caused muscular hypotonia. All potential interacting agents were given as pretreatments to determine changes in motor function which may interfere with the climbing induced by 1.0 mg/kg s.c. apomorphine. The possibility of a change in the apomorphine response to a sterotyped biting, which would also interfere with climbing, was also considered. Excluding these non-specific changes, climbing behaviour was shown to be antagonised, dose-dependently, by low doses of typical and atypical neuroleptic agents (haloperidol, fluphenazine, loxapine, pimozide, oxiperomide, clozapin, thioridazine, sulpiride, tiapride and metoclopramide) but not specifically by other psychoactive agents. Climbing behaviour was modified by serotonergic agents; the agonist quipazine reduced or abolished, whilst the antagonists, methysergide and cyproheptadine, enhanced the response. Picrotoxin specifically reduced climbing behaviour but sodium valproate exerted non-specific effects, precluding conclusions as to a GABA involvement. Cholinergic and noradrenergic involvements with climbing were also apparently eliminated by the ineffectiveness of atropine, aceperone, piperoxan and propranolol. The involvement of serotonin with climbing was extended to the actions of the neuroleptics: the antagonistic effects of typical neuroleptics (haloperidol, fluphenazine, loxapine) were markedly enhanced by combination with methysergide or cyproheptadine whilst the effects of clozapine, sulpiride and thioridazine were significantly reduced. The actions of metoclopramide, oxiperomide, pimozide and tiapride were not generally modified by such combinations. These differences are discussed in terms of differential abilities to induce extrapyramidal disturbances and the mouse climbing model is forwarded as a test with potential to detect antipsychotic agents of different activity spectra.", "contents": "Climbing behaviour induced by apomorphine in mice: a potential model for the detection of neuroleptic activity. Apomorphine and the putative dopamine agonist, 2-(N, N-dipropyl)-amino-5, 6-dihydroxytetralin induced dose-dependent climbing behaviour in the mouse which was measured in wire mesh lined cages as the percentage of time spent climbing in the 30 min period following the first climb and as the maximum time spent in a single climb throughout the drug effect. These These two measures were generally found to parallel excepting when the interacting agent caused muscular hypotonia. All potential interacting agents were given as pretreatments to determine changes in motor function which may interfere with the climbing induced by 1.0 mg/kg s.c. apomorphine. The possibility of a change in the apomorphine response to a sterotyped biting, which would also interfere with climbing, was also considered. Excluding these non-specific changes, climbing behaviour was shown to be antagonised, dose-dependently, by low doses of typical and atypical neuroleptic agents (haloperidol, fluphenazine, loxapine, pimozide, oxiperomide, clozapin, thioridazine, sulpiride, tiapride and metoclopramide) but not specifically by other psychoactive agents. Climbing behaviour was modified by serotonergic agents; the agonist quipazine reduced or abolished, whilst the antagonists, methysergide and cyproheptadine, enhanced the response. Picrotoxin specifically reduced climbing behaviour but sodium valproate exerted non-specific effects, precluding conclusions as to a GABA involvement. Cholinergic and noradrenergic involvements with climbing were also apparently eliminated by the ineffectiveness of atropine, aceperone, piperoxan and propranolol. The involvement of serotonin with climbing was extended to the actions of the neuroleptics: the antagonistic effects of typical neuroleptics (haloperidol, fluphenazine, loxapine) were markedly enhanced by combination with methysergide or cyproheptadine whilst the effects of clozapine, sulpiride and thioridazine were significantly reduced. The actions of metoclopramide, oxiperomide, pimozide and tiapride were not generally modified by such combinations. These differences are discussed in terms of differential abilities to induce extrapyramidal disturbances and the mouse climbing model is forwarded as a test with potential to detect antipsychotic agents of different activity spectra."}
{"id": "PMID:28234", "title": "The influence of heart rate on ouabain cardiotoxicity in cats with spinal cord transection.", "content": "The dose, serum level and ventricular content of ouabain needed to produce cardiotoxicity were examined in control cats, cats with transected spinal cords and cats with transected spinal cords whose heart rates were restored to control values by artificial pacing. The lethal dose of ouabain was higher in cats with transected spinal cords and not paced than it was in the control group. However, the lethal dose of ouabain in spinal-sectioned cats with ventricular pacing was no different from that in controls. However, in both groups of spinal-sectioned cats, death was associated with higher ventricular and serum levels of ouabain than in controls. The ventricular ouabain content of paced animals with transected spinal cords was higher than that of controls and lower than that of unpaced spinal cats. Thus, restoration of heart rate to control levels in spinal animals appeared to accelerate myocardial ouabain uptake. The lower myocardial ouabain content in the spinal-sectioned animals which were paced suggests that pacing sensitizes the heart to cardiotoxicity. Spinal section itself appears to decrease the sensitivity to ouabain partly through a decrease in cardiac rate and partly through a loss of neurogenic influence.", "contents": "The influence of heart rate on ouabain cardiotoxicity in cats with spinal cord transection. The dose, serum level and ventricular content of ouabain needed to produce cardiotoxicity were examined in control cats, cats with transected spinal cords and cats with transected spinal cords whose heart rates were restored to control values by artificial pacing. The lethal dose of ouabain was higher in cats with transected spinal cords and not paced than it was in the control group. However, the lethal dose of ouabain in spinal-sectioned cats with ventricular pacing was no different from that in controls. However, in both groups of spinal-sectioned cats, death was associated with higher ventricular and serum levels of ouabain than in controls. The ventricular ouabain content of paced animals with transected spinal cords was higher than that of controls and lower than that of unpaced spinal cats. Thus, restoration of heart rate to control levels in spinal animals appeared to accelerate myocardial ouabain uptake. The lower myocardial ouabain content in the spinal-sectioned animals which were paced suggests that pacing sensitizes the heart to cardiotoxicity. Spinal section itself appears to decrease the sensitivity to ouabain partly through a decrease in cardiac rate and partly through a loss of neurogenic influence."}
{"id": "PMID:28236", "title": "Halothane-induced sleeping time in the mouse: its modification by benzodiazepines.", "content": "The conditions under which prolongation of halothane-induced sleeping time in the mouse may be used as a test for centrally acting drugs are described. The test can be recommended for its practical advantages over methods using barbiturates to induce hypnosis; due cognizance must be taken of a diurnal variation in the response of mice to halothane. To assess the usefulness of the test the effects of amphetamine, chlorpromazine, histamine, morphine, nikethamide, pentobarbitone and SKF 525A have been investigated. The interaction between 5 benzodiazepines and halothane has been studied in particular. Results from sleeping time experiments, measurements of body temperature and of brain halothane concentrations suggest that the halothane-benzodiazepine interaction is due to additive CNS depressant effects. It was found that nitrazepam and diazepam were clearly more potent than chlorodiazepoxide, medazepam and oxazepam in respect of their interactions with halothane.", "contents": "Halothane-induced sleeping time in the mouse: its modification by benzodiazepines. The conditions under which prolongation of halothane-induced sleeping time in the mouse may be used as a test for centrally acting drugs are described. The test can be recommended for its practical advantages over methods using barbiturates to induce hypnosis; due cognizance must be taken of a diurnal variation in the response of mice to halothane. To assess the usefulness of the test the effects of amphetamine, chlorpromazine, histamine, morphine, nikethamide, pentobarbitone and SKF 525A have been investigated. The interaction between 5 benzodiazepines and halothane has been studied in particular. Results from sleeping time experiments, measurements of body temperature and of brain halothane concentrations suggest that the halothane-benzodiazepine interaction is due to additive CNS depressant effects. It was found that nitrazepam and diazepam were clearly more potent than chlorodiazepoxide, medazepam and oxazepam in respect of their interactions with halothane."}
{"id": "PMID:28237", "title": "Relaxation of depolarized guinea pig taenia caecum induced by some antispasmodics.", "content": "Taenia isolated from the guinea pig caecum were used for the experiments. No inhibitory response of the depolarized taenia to isoprenaline was observed during the significant increase of cyclic AMP level. These observations suggest that the total tissue level of cyclic AMP is not an important determinant of relaxation in the depolarized taenia. Antispasmodics, such as papaverine, benactyzine and Aspaminol (1,1-diphenyl-3-piperidino-butanol hydrochloride) relaxed the depolarized taenia, while the depolarized taenia was not relaxed by concentrations of dibutyryl cyclic AMP sufficient to relax the polarized taenia. Ca uptake by the depolarized taenia was inhibited by papaverine, benactyzine and Aspaminol but not by isoprenaline and dibutyryl cyclic AMP. These results indicate that relaxation of the depolarized taenia induced by the antispasmodics used was mainly due to inhibition of Ca uptake.", "contents": "Relaxation of depolarized guinea pig taenia caecum induced by some antispasmodics. Taenia isolated from the guinea pig caecum were used for the experiments. No inhibitory response of the depolarized taenia to isoprenaline was observed during the significant increase of cyclic AMP level. These observations suggest that the total tissue level of cyclic AMP is not an important determinant of relaxation in the depolarized taenia. Antispasmodics, such as papaverine, benactyzine and Aspaminol (1,1-diphenyl-3-piperidino-butanol hydrochloride) relaxed the depolarized taenia, while the depolarized taenia was not relaxed by concentrations of dibutyryl cyclic AMP sufficient to relax the polarized taenia. Ca uptake by the depolarized taenia was inhibited by papaverine, benactyzine and Aspaminol but not by isoprenaline and dibutyryl cyclic AMP. These results indicate that relaxation of the depolarized taenia induced by the antispasmodics used was mainly due to inhibition of Ca uptake."}
{"id": "PMID:28250", "title": "Steric aspects of dopaminergic drugs.", "content": "There are a variety of molecule species of dopamine avaialable at physiological pH. The predominant form available at physiological pH is the phenolic ammonium salt. However, at the present time the molecular form that is optimum for producing dopaminergic activity is unknown. In attempting to delineate the conformational requirements of dopaminergic agonists, a variety of conformationally restricted analogs and complex molecules possessing a dopaminergic segment have been investigated. It appears at this time that the trans extended form of dopamine is the optimum form for binding to dopamine receptors. The rotameric forms of dopamine are also important considerations when examining a molecule for dopaminergic agonist activity. A high degree of stereospecificity has been shown in different dopaminergic systems.", "contents": "Steric aspects of dopaminergic drugs. There are a variety of molecule species of dopamine avaialable at physiological pH. The predominant form available at physiological pH is the phenolic ammonium salt. However, at the present time the molecular form that is optimum for producing dopaminergic activity is unknown. In attempting to delineate the conformational requirements of dopaminergic agonists, a variety of conformationally restricted analogs and complex molecules possessing a dopaminergic segment have been investigated. It appears at this time that the trans extended form of dopamine is the optimum form for binding to dopamine receptors. The rotameric forms of dopamine are also important considerations when examining a molecule for dopaminergic agonist activity. A high degree of stereospecificity has been shown in different dopaminergic systems."}
{"id": "PMID:28254", "title": "[Several new inhibitors of gastric secretion].", "content": "In experiments on dogs, milid (proglymid) entailed a weak inhibition of the 2nd phase of the gastric secretion leaving intact the 1st phase. The action of LS-519 was obvious in the 1st phase, having entailed a significant inhibition. The glycomacropeptid exerted a strong inhibiting effect both on the 1st and the 2nd phases, the effect lasting longer than that of the first two drugs. All the three drugs not only inhibited the gastric secretion but increased pH, reduced the gastric juice acidity while exerting no significan effect on concentration of common proteinases.", "contents": "[Several new inhibitors of gastric secretion]. In experiments on dogs, milid (proglymid) entailed a weak inhibition of the 2nd phase of the gastric secretion leaving intact the 1st phase. The action of LS-519 was obvious in the 1st phase, having entailed a significant inhibition. The glycomacropeptid exerted a strong inhibiting effect both on the 1st and the 2nd phases, the effect lasting longer than that of the first two drugs. All the three drugs not only inhibited the gastric secretion but increased pH, reduced the gastric juice acidity while exerting no significan effect on concentration of common proteinases."}
{"id": "PMID:28255", "title": "Ergonomics. Reducing mental and physical fatigue in the dental operatory.", "content": "The work output and the mental and physical fatigue generated by a dental procedure is affected by the length and type of operation, physical facilities, the amount of cooperation given by the patient, operating techniques, and the effective teamwork and rapport of the operatory dental team. Fatigue is also generated by stresses that arise outside of the office and which, when superimposed over the normal operating stresses of the office, can have a cumulative effect of decreasing output and increasing mental and physical fatigue for the dentist, the assistant, and the patient. Probably the three most important means to compensate for both routine and nonroutine physical and mental stresses of any type or origin are: (1) learn to cope with or resolve the origin of the stress; (2) develop a pattern of healthy living; (3) cultivate job satisfaction.", "contents": "Ergonomics. Reducing mental and physical fatigue in the dental operatory. The work output and the mental and physical fatigue generated by a dental procedure is affected by the length and type of operation, physical facilities, the amount of cooperation given by the patient, operating techniques, and the effective teamwork and rapport of the operatory dental team. Fatigue is also generated by stresses that arise outside of the office and which, when superimposed over the normal operating stresses of the office, can have a cumulative effect of decreasing output and increasing mental and physical fatigue for the dentist, the assistant, and the patient. Probably the three most important means to compensate for both routine and nonroutine physical and mental stresses of any type or origin are: (1) learn to cope with or resolve the origin of the stress; (2) develop a pattern of healthy living; (3) cultivate job satisfaction."}
{"id": "PMID:28260", "title": "Adenylate cyclase of human gastric mucosa. Stimulation of enzyme activity by histamine and catecholamines.", "content": "Human gastric mucosal adenylate cyclase has been shown to be sensitive to histamine and catecholamines. Stimulation of enzyme activity by histamine and catecholamines were selectively blocked by cimetidine and propranolol, respectively. Combination of both hormones at maximally effective concentrations were additive, indicating that human gastric mucosa contains at least two separate hormone-sensitive adenylate cyclases.", "contents": "Adenylate cyclase of human gastric mucosa. Stimulation of enzyme activity by histamine and catecholamines. Human gastric mucosal adenylate cyclase has been shown to be sensitive to histamine and catecholamines. Stimulation of enzyme activity by histamine and catecholamines were selectively blocked by cimetidine and propranolol, respectively. Combination of both hormones at maximally effective concentrations were additive, indicating that human gastric mucosa contains at least two separate hormone-sensitive adenylate cyclases."}
{"id": "PMID:28261", "title": "Fecal chymotrypsin: study on some characteristics of the enzyme.", "content": "A Lineweaver-Burk plot demonstrated that the apparent Michaelis constants are identical for chymotrypsin (CT) in duodenal juice and in feces of the same patient. CT in fecal homogenates exhibits exhibits a remarkable stability and is bound to particles to a considerable but variable extent. The pH optimum of CT in human feces is somewhat higher as compared to pure bovine pancreatic CT. All measurements of fecal CT activity should, therefore, be performed at pH 9.0. The distribution of CT among the fecal mass has been investigated. There were considerable differences between CT activities in random fecal specimens and in the corresponding stool collections. However, if the results were expressed in terms of 'normal' and 'abnormal', 113 out of 120 random fecal specimens gave the same results as the corresponding stool collections. It is concluded that the risk of 'false-normal' values cannot be effectively reduced by determination of CT outputs in stool collections (or by using continuous markers) instead of CT activities in random stool specimens.", "contents": "Fecal chymotrypsin: study on some characteristics of the enzyme. A Lineweaver-Burk plot demonstrated that the apparent Michaelis constants are identical for chymotrypsin (CT) in duodenal juice and in feces of the same patient. CT in fecal homogenates exhibits exhibits a remarkable stability and is bound to particles to a considerable but variable extent. The pH optimum of CT in human feces is somewhat higher as compared to pure bovine pancreatic CT. All measurements of fecal CT activity should, therefore, be performed at pH 9.0. The distribution of CT among the fecal mass has been investigated. There were considerable differences between CT activities in random fecal specimens and in the corresponding stool collections. However, if the results were expressed in terms of 'normal' and 'abnormal', 113 out of 120 random fecal specimens gave the same results as the corresponding stool collections. It is concluded that the risk of 'false-normal' values cannot be effectively reduced by determination of CT outputs in stool collections (or by using continuous markers) instead of CT activities in random stool specimens."}
{"id": "PMID:28263", "title": "Polyarteritis nodosa causing severe intestinal bleeding.", "content": "Rupture of an aneurysm of the mesentergic artery caused severe intestinal hemorrhage in a 50-year-old woman with polyarteritis nodosa. Abdominal angiography not only established diagnosis of polyarteritis nodosa by demonstrating multiple visceral aneurysms but also localized the site of bleeding.", "contents": "Polyarteritis nodosa causing severe intestinal bleeding. Rupture of an aneurysm of the mesentergic artery caused severe intestinal hemorrhage in a 50-year-old woman with polyarteritis nodosa. Abdominal angiography not only established diagnosis of polyarteritis nodosa by demonstrating multiple visceral aneurysms but also localized the site of bleeding."}
{"id": "PMID:28264", "title": "Non-beta islet cell tumor calcification assoicated with Zollinger-Ellison syndrome and multiple endocrine adenomatosis.", "content": "The radiographic triad of a calcified pancreatic mass, duodenal ulcers, and nephrocalcinosis should suggest the Zollinger-Ellison syndrome, as part of the multiple endocrine adenomatosis complex. The clinical and radiographic features of the entity are described in this case report.", "contents": "Non-beta islet cell tumor calcification assoicated with Zollinger-Ellison syndrome and multiple endocrine adenomatosis. The radiographic triad of a calcified pancreatic mass, duodenal ulcers, and nephrocalcinosis should suggest the Zollinger-Ellison syndrome, as part of the multiple endocrine adenomatosis complex. The clinical and radiographic features of the entity are described in this case report."}
{"id": "PMID:28269", "title": "Recognition of alcoholic liver disease in a district general hospital.", "content": "Two-hundred-and-two patients with alcoholic liver disease whose investigations included a liver biopsy were seen in a district general hospital over a seven year period. Thirty-five percent presented with general gastrointestinal symptoms rather than with overt liver disease or previously recognised excess consumption of alcohol. Recognition of the alcohol problem was assisted by the finding of a raised mean corpuscular volume (MCV) and/or gammaglutamyl transpeptidase (GGTP). The use of these methods of detection is discussed in relation to the rapid rise in alcohol consumption in the United Kingdom, and the high mortality of cirrhosis reported from special centres. Twnety-two per cent of the patients were found to have an established cirrhosis, and there was some evidence that the women were more susceptible to some of the toxic effects of alcohol. Early detection can be enhanced by a high level of suspicion, wider recognition of the significance of a high MCV, and the greater use of GGTP estimations.", "contents": "Recognition of alcoholic liver disease in a district general hospital. Two-hundred-and-two patients with alcoholic liver disease whose investigations included a liver biopsy were seen in a district general hospital over a seven year period. Thirty-five percent presented with general gastrointestinal symptoms rather than with overt liver disease or previously recognised excess consumption of alcohol. Recognition of the alcohol problem was assisted by the finding of a raised mean corpuscular volume (MCV) and/or gammaglutamyl transpeptidase (GGTP). The use of these methods of detection is discussed in relation to the rapid rise in alcohol consumption in the United Kingdom, and the high mortality of cirrhosis reported from special centres. Twnety-two per cent of the patients were found to have an established cirrhosis, and there was some evidence that the women were more susceptible to some of the toxic effects of alcohol. Early detection can be enhanced by a high level of suspicion, wider recognition of the significance of a high MCV, and the greater use of GGTP estimations."}
{"id": "PMID:28270", "title": "Postprandial duodenal function in man.", "content": "Duodenal function was studied in 11 healthy volunteers after intragastric instillation of a mixed semi-elemental meal. The duodenum accepted chyme of varying pH, osmolality, and nutrient concentration; and, as a result of biliary, pancreatic, and enteric secretion as well as absorption, it delivered chyme with nearly constant pH, osmolality, and nutrient concentration to the jejunum. The flow rate and nutrient load of jejunal chyme varied. The duodenum absorbed more carbohydrate than lipid and less protein, taking up each nutrient at a constant rate during most of the postprandial period. The percentage of nutrient load absorbed was greatest in the late postprandial period, when flow rate, nutrient load, and concentrations were low.", "contents": "Postprandial duodenal function in man. Duodenal function was studied in 11 healthy volunteers after intragastric instillation of a mixed semi-elemental meal. The duodenum accepted chyme of varying pH, osmolality, and nutrient concentration; and, as a result of biliary, pancreatic, and enteric secretion as well as absorption, it delivered chyme with nearly constant pH, osmolality, and nutrient concentration to the jejunum. The flow rate and nutrient load of jejunal chyme varied. The duodenum absorbed more carbohydrate than lipid and less protein, taking up each nutrient at a constant rate during most of the postprandial period. The percentage of nutrient load absorbed was greatest in the late postprandial period, when flow rate, nutrient load, and concentrations were low."}
{"id": "PMID:28271", "title": "Acid microclimate in coeliac and Crohn's disease: a model for folate malabsorption.", "content": "The surface pH of human proximal jejunum was measured in biopsy samples and found to be more acid than the phosphate buffer in which they were incubated. The in vitro jejunal surface pH was 5.93 +/- 0.05 in control subjects and 6.19 +/- 0.09 in treated coeliac patients. A group of untreated coeliac patients with a surface pH of 6.56 +/- 0.14 had a significantly less acid surface pH compared to controls, as did a group of Crohn's patients with a surface pH of 6.21 +/- 0.04. These two groups with a significantly raised surface pH were subdivisible into 'high' and 'low'groups. Surface pH was found to remain low in the treated coeliac and control groups but became more acid over the incubation period reaching almost normal values in the Crohn's group and the untreated coelic initial surface pH. The raised surface pH in untreated coeliac disease and Crohn's disease would alter the amount of a weak acid available for non-ionic diffusion. Therefore the present results may help to explain the folate malabsorption known to occur in untreated coeliac disease and the frequently seen low serum folate levels in Crohn's disease.", "contents": "Acid microclimate in coeliac and Crohn's disease: a model for folate malabsorption. The surface pH of human proximal jejunum was measured in biopsy samples and found to be more acid than the phosphate buffer in which they were incubated. The in vitro jejunal surface pH was 5.93 +/- 0.05 in control subjects and 6.19 +/- 0.09 in treated coeliac patients. A group of untreated coeliac patients with a surface pH of 6.56 +/- 0.14 had a significantly less acid surface pH compared to controls, as did a group of Crohn's patients with a surface pH of 6.21 +/- 0.04. These two groups with a significantly raised surface pH were subdivisible into 'high' and 'low'groups. Surface pH was found to remain low in the treated coeliac and control groups but became more acid over the incubation period reaching almost normal values in the Crohn's group and the untreated coelic initial surface pH. The raised surface pH in untreated coeliac disease and Crohn's disease would alter the amount of a weak acid available for non-ionic diffusion. Therefore the present results may help to explain the folate malabsorption known to occur in untreated coeliac disease and the frequently seen low serum folate levels in Crohn's disease."}
{"id": "PMID:28272", "title": "Effects of phospholipase A and triton x-100 on guanylate cyclase activity in mammary gland homogenates from mice.", "content": "The effects of a variety of agents on guanylate cyclase activity were tested in broken cell preparations of mammary glands from midpregnant mice. Of the agents tested, only phospholipase A, triton X-100, and an impure egg lysolecithin preparation enhanced the activity of guanylate cyclase in mammary gland homogenates; other agents, including sodium azide and phospholipase C, and purified egg lysolecithin had no effect. Phospholipase A increased the activity of guanylate cyclase in the 150,000 g pellet fractions of mammary gland homogenates, bud did not consistently enhance guanylate cyclase in the 150,000 g supernatant fractions. Phospholipase A did not appear to enhance guanylate cyclase activity by solublizing the enzyme from the 150,000 g pellet. Triton X-100, in contrast, appeared to act by solubilizing guanylate cyclase from the material present in the 150,000 g pellet. Triton X-100 increased by several fold guanylate cyclase activity in the tissue homogenates and the 150,000 g pellets, but did not consistently enhance enzyme activity in the 150,000 g supernatant. Triton X-100 had no effect on the apparent Km of guanylate cyclase.", "contents": "Effects of phospholipase A and triton x-100 on guanylate cyclase activity in mammary gland homogenates from mice. The effects of a variety of agents on guanylate cyclase activity were tested in broken cell preparations of mammary glands from midpregnant mice. Of the agents tested, only phospholipase A, triton X-100, and an impure egg lysolecithin preparation enhanced the activity of guanylate cyclase in mammary gland homogenates; other agents, including sodium azide and phospholipase C, and purified egg lysolecithin had no effect. Phospholipase A increased the activity of guanylate cyclase in the 150,000 g pellet fractions of mammary gland homogenates, bud did not consistently enhance guanylate cyclase in the 150,000 g supernatant fractions. Phospholipase A did not appear to enhance guanylate cyclase activity by solublizing the enzyme from the 150,000 g pellet. Triton X-100, in contrast, appeared to act by solubilizing guanylate cyclase from the material present in the 150,000 g pellet. Triton X-100 increased by several fold guanylate cyclase activity in the tissue homogenates and the 150,000 g pellets, but did not consistently enhance enzyme activity in the 150,000 g supernatant. Triton X-100 had no effect on the apparent Km of guanylate cyclase."}
{"id": "PMID:28274", "title": "Rapid formation of N-nitrosamines from nitrogen oxides under neutral and alkaline conditions.", "content": "The formation of carcinogenic N-nitrosamines in neutral and alkaline aqueous solutions (pH 6-14) at 25 degrees C is reported using dissolved N2O3 and N2O4 gases. These reactions are very much faster than those with acidified nitrite: typically, 2 X 10(-3) M amine gives ca. 10-50% N-nitrosamine in a few seconds with 5-20 fold excess of nitrogen oxide. The N-nitrosamine yield in 0.1 M sodium hydroxide is independent of amine basicity from pKA 11.2-0.99, but decreases with decreasing pH of the reaction solution for the more basic amines. Significantly, N-nitrosamine yields are not lowered with diluted nitrogen oxides (1000 ppm) and moderately basic amines (eg. N-methylpiperazine) react readily at physiological pH. The mechanism by which these reactions occur is discussed, with particular reference to the existence of two reactive tautomeric forms of N2O3 and N2O4. The formation of carcinogenic N-nitrosamines from NO in ethanol at 25 degrees C is also reported. These reactions are slow in the absence of air (oxygen), I2 or metal salts. Oxygen accelerates nitrosation by converting NO via NO2 to either N2O3 or N2O4, but both I2 and metal salts are effective under anaerobic conditions, where reaction rates are virtually independent of amine basicity but depend on the nature of the added reagent. The most effective substance is I2, which gives quantitative yields of N-nitrosamine in a few minutes at 25 degrees C by forming the reactive nitrosyl iodide (NOI) reagent. Acceleration in ethanol at 25 degrees C is also observed with AgI, CuI, CuII, ZnII, FeIII and CoII salts, among others, with substantial amounts of N-nitrosamine being produced in ca. 30-300 min. Metal iodides intervene by way of the NOI reagent, as for I2, but other salts require a mechanism involving reaction between a metal-amine complex and NO, itself. The results show that carcinogenic N-nitrosamines may form under a much wider range of experimental conditions than suspected hitherto. Their relevance to human exposure is discussed, with particular reference to urban pollution and the effect of dietary antioxidants.", "contents": "Rapid formation of N-nitrosamines from nitrogen oxides under neutral and alkaline conditions. The formation of carcinogenic N-nitrosamines in neutral and alkaline aqueous solutions (pH 6-14) at 25 degrees C is reported using dissolved N2O3 and N2O4 gases. These reactions are very much faster than those with acidified nitrite: typically, 2 X 10(-3) M amine gives ca. 10-50% N-nitrosamine in a few seconds with 5-20 fold excess of nitrogen oxide. The N-nitrosamine yield in 0.1 M sodium hydroxide is independent of amine basicity from pKA 11.2-0.99, but decreases with decreasing pH of the reaction solution for the more basic amines. Significantly, N-nitrosamine yields are not lowered with diluted nitrogen oxides (1000 ppm) and moderately basic amines (eg. N-methylpiperazine) react readily at physiological pH. The mechanism by which these reactions occur is discussed, with particular reference to the existence of two reactive tautomeric forms of N2O3 and N2O4. The formation of carcinogenic N-nitrosamines from NO in ethanol at 25 degrees C is also reported. These reactions are slow in the absence of air (oxygen), I2 or metal salts. Oxygen accelerates nitrosation by converting NO via NO2 to either N2O3 or N2O4, but both I2 and metal salts are effective under anaerobic conditions, where reaction rates are virtually independent of amine basicity but depend on the nature of the added reagent. The most effective substance is I2, which gives quantitative yields of N-nitrosamine in a few minutes at 25 degrees C by forming the reactive nitrosyl iodide (NOI) reagent. Acceleration in ethanol at 25 degrees C is also observed with AgI, CuI, CuII, ZnII, FeIII and CoII salts, among others, with substantial amounts of N-nitrosamine being produced in ca. 30-300 min. Metal iodides intervene by way of the NOI reagent, as for I2, but other salts require a mechanism involving reaction between a metal-amine complex and NO, itself. The results show that carcinogenic N-nitrosamines may form under a much wider range of experimental conditions than suspected hitherto. Their relevance to human exposure is discussed, with particular reference to urban pollution and the effect of dietary antioxidants."}
{"id": "PMID:28275", "title": "Mechanism of N-nitrosodimethylamine formation from trimethylamine and trimethylaminoxide.", "content": "The kinetics of nitrosation of trimethylamine (TMA) and trimethylaminoxide (TMAO) to give N-nitrosodimethylamine (NDMA) have been studied. The nitrosation rates of TMA and TMAO, when determined at 100 degrees C in sealed tubes, showed maximum values at about pH 3, while at temperatures lower than 75 degrees C the pH dependence of the nitrosation of these compounds was similar to that observed with alkylamides. The initial rate of NDMA formation from TMAO determined at pH 3.0 and 25 degrees C was found to be proportional to the TMAO and nitrite concentrations, not to the square of the nitrite concentration. In contrast, the rates of NDMA formation from TMA and TMAO when reacted at pH 3.0 and 100 degrees C in sealed tubes were found to be proportional to the square and the cube, respectively, of the nitrite concentration. These results strongly suggest that the NDMA formation at higher temperatures involves the oxidative cleavage of tertiary amines to produce secondary amines (dimethylamine, DMA) which may react with nitrite to form NDMA. On the other hand, at lower temperatures, NDMA may be formed from TMA or TMAO by a pathway not involving DMA.", "contents": "Mechanism of N-nitrosodimethylamine formation from trimethylamine and trimethylaminoxide. The kinetics of nitrosation of trimethylamine (TMA) and trimethylaminoxide (TMAO) to give N-nitrosodimethylamine (NDMA) have been studied. The nitrosation rates of TMA and TMAO, when determined at 100 degrees C in sealed tubes, showed maximum values at about pH 3, while at temperatures lower than 75 degrees C the pH dependence of the nitrosation of these compounds was similar to that observed with alkylamides. The initial rate of NDMA formation from TMAO determined at pH 3.0 and 25 degrees C was found to be proportional to the TMAO and nitrite concentrations, not to the square of the nitrite concentration. In contrast, the rates of NDMA formation from TMA and TMAO when reacted at pH 3.0 and 100 degrees C in sealed tubes were found to be proportional to the square and the cube, respectively, of the nitrite concentration. These results strongly suggest that the NDMA formation at higher temperatures involves the oxidative cleavage of tertiary amines to produce secondary amines (dimethylamine, DMA) which may react with nitrite to form NDMA. On the other hand, at lower temperatures, NDMA may be formed from TMA or TMAO by a pathway not involving DMA."}
{"id": "PMID:28276", "title": "Some effects of phenol- and thiol-nitrosation reactions on N-nitrosamine formation.", "content": "C-Nitrosophenols, produced by the nitrosation of phenols, catalyse N-nitrosamine formation. The rate of N-nitrosation of pyrrolidine, catalysed by p-nitroso-o-cresol, is fastest at about pH 5. The catalytic species is thought to be the quinone monoxime tautomer of the nitrosophenol. A possible mechanism for the catalysis is proposed. A reaction of pyrrolidine with nitrite at pH 5.0 is described, which gives enhanced N-nitrosation in the presence of p-cresol. The yield of N-nitrosopyrrolidine (NPYR) is further enhanced when this reaction is carried out under anaerobic conditions. Nitrosocysteine hydrochloride reacts with N-methylaniline at pH 2.65, 5.5 and 9.75 in the absence of nitrite to give N-nitroso N-methylaniline. The N-nitrosation of morpholine and pyrrolidine at pH 9.75 is also effected by nitrosocysteine hydrochloride. The rate of N-nitrosation at this pH decreases with increasing amine basicity. The reaction of nitrosocysteine with N-methylaniline at pH 9.75 under anaerobic conditions leads to a significant reduction in the yield of N-nitroso-N-methylaniline.", "contents": "Some effects of phenol- and thiol-nitrosation reactions on N-nitrosamine formation. C-Nitrosophenols, produced by the nitrosation of phenols, catalyse N-nitrosamine formation. The rate of N-nitrosation of pyrrolidine, catalysed by p-nitroso-o-cresol, is fastest at about pH 5. The catalytic species is thought to be the quinone monoxime tautomer of the nitrosophenol. A possible mechanism for the catalysis is proposed. A reaction of pyrrolidine with nitrite at pH 5.0 is described, which gives enhanced N-nitrosation in the presence of p-cresol. The yield of N-nitrosopyrrolidine (NPYR) is further enhanced when this reaction is carried out under anaerobic conditions. Nitrosocysteine hydrochloride reacts with N-methylaniline at pH 2.65, 5.5 and 9.75 in the absence of nitrite to give N-nitroso N-methylaniline. The N-nitrosation of morpholine and pyrrolidine at pH 9.75 is also effected by nitrosocysteine hydrochloride. The rate of N-nitrosation at this pH decreases with increasing amine basicity. The reaction of nitrosocysteine with N-methylaniline at pH 9.75 under anaerobic conditions leads to a significant reduction in the yield of N-nitroso-N-methylaniline."}
{"id": "PMID:28277", "title": "Alpha-tocopherol: uses in preventing nitrosamine formation.", "content": "alpha-Tocopherol has been evaluated as a nitrite scavenger for the prevention of nitrosamine formation in a model system and under practical conditions. alpha-Tocopherol was found to react with nitrosating agents in both lipophilic and aqueous environments. The use of alpha-tocopherol was shown to inhibit aminopyrene-nitrite induced hepatotoxicity in rats and to reduce the amount of NDMA formed in cigarette smoke. Of primary interest is the finding of a significant reduction of NPYR formation in fried bacon. Nitrosamine inhibition was greater with alpha-tocopherol used in combination with sodium ascorbate than with sodium ascorbate alone.", "contents": "Alpha-tocopherol: uses in preventing nitrosamine formation. alpha-Tocopherol has been evaluated as a nitrite scavenger for the prevention of nitrosamine formation in a model system and under practical conditions. alpha-Tocopherol was found to react with nitrosating agents in both lipophilic and aqueous environments. The use of alpha-tocopherol was shown to inhibit aminopyrene-nitrite induced hepatotoxicity in rats and to reduce the amount of NDMA formed in cigarette smoke. Of primary interest is the finding of a significant reduction of NPYR formation in fried bacon. Nitrosamine inhibition was greater with alpha-tocopherol used in combination with sodium ascorbate than with sodium ascorbate alone."}
{"id": "PMID:28279", "title": "Acceleration of nitrosamine formation at pH 3.5 by microorganisms.", "content": "Rate enhancements of from 12 to 49-fold occurred when dihexylamine was nitrosated at pH 3.5 in the presence of bacteria and yeast cells at a concentration of 12 mg/ml. Rates were similar in the presence of either boiled or unheated cells. The magnitude of the rate enhancement for nitrosation of other amines depended on the alkyl chain length. A nonenzymatic mechanism involving hydrophobic interactions of the precursor amines and cellular constituents is proposed.", "contents": "Acceleration of nitrosamine formation at pH 3.5 by microorganisms. Rate enhancements of from 12 to 49-fold occurred when dihexylamine was nitrosated at pH 3.5 in the presence of bacteria and yeast cells at a concentration of 12 mg/ml. Rates were similar in the presence of either boiled or unheated cells. The magnitude of the rate enhancement for nitrosation of other amines depended on the alkyl chain length. A nonenzymatic mechanism involving hydrophobic interactions of the precursor amines and cellular constituents is proposed."}
{"id": "PMID:28282", "title": "Preliminary observations on amines and nitrosamines in non-normal human gastric contents.", "content": "Gastric contents from fasting humans were pooled and analysed for amines. Volatile amines present were dimethylamine, trimethylamine and histamine; non-volatile amines found were cadaverine, putrescine, ethanolamine and tryptamine. Gastric contents from 35 patients, some before and/or after gastric stimulation with histamine or pentagastrin, were analysed for nitrosamines. N-Nitrosodiethylamine (NDEA) (5-30 microgram/kg) was present in four samples, N-nitrosodimethylamine (NDMA) (2 microgram/kg) in two samples and N-nitrosopyrrolidine (NPYR) (6 microgram/kg) in one sample. pH, nitrite and nitrate determinations were made on some samples. Medical diagnosis of patients could not be correlated with the presence of nitrosamines in the gastric contents.", "contents": "Preliminary observations on amines and nitrosamines in non-normal human gastric contents. Gastric contents from fasting humans were pooled and analysed for amines. Volatile amines present were dimethylamine, trimethylamine and histamine; non-volatile amines found were cadaverine, putrescine, ethanolamine and tryptamine. Gastric contents from 35 patients, some before and/or after gastric stimulation with histamine or pentagastrin, were analysed for nitrosamines. N-Nitrosodiethylamine (NDEA) (5-30 microgram/kg) was present in four samples, N-nitrosodimethylamine (NDMA) (2 microgram/kg) in two samples and N-nitrosopyrrolidine (NPYR) (6 microgram/kg) in one sample. pH, nitrite and nitrate determinations were made on some samples. Medical diagnosis of patients could not be correlated with the presence of nitrosamines in the gastric contents."}
{"id": "PMID:28285", "title": "Homologous and cross-reactive precipitins in anti-pneumococcal sera raised in mules.", "content": "Serial bleedings were obtained from two mules during prolonged immunization, one with type XXV the other with type VIII pneumococcal vaccine. IgGa, IgGb, IgGc, IgB, IgG(T) and IgM present among purified Pn anti-XXV and Pn anti-VIII immunoglobulin isolated from various bleedings were identified by use of rabbit anti-equine heavy chain specific reagents. Radioimmunodiffusion with 14C-labelled type XXV pneumococcal capsular polysaccharide and horse and donkey reagents with species specificity directed against donkey or horse IgGa respectively, demonstrated both parental horse and donkey IgGa heavy chain isotypes among the anti-PnXXV antibodies of the interspecies hybrid. Qualtitative and quantitative examination of the cross-precipitation of mule anti-PnXXV sera with the capsular polysaccharides of pneumococcal types IV, X and XA, with birch sap, ketha gum, and with polysaccharides of E. coli, Klebsiella and Rhizobium was carried out and compared with data obtained with anti-PnXXV raised in a horse. Analysis of supernatants from the cross-reactions showed that distinct subfractions had reacted. indicating a marked heterogeneity of the antibodies.", "contents": "Homologous and cross-reactive precipitins in anti-pneumococcal sera raised in mules. Serial bleedings were obtained from two mules during prolonged immunization, one with type XXV the other with type VIII pneumococcal vaccine. IgGa, IgGb, IgGc, IgB, IgG(T) and IgM present among purified Pn anti-XXV and Pn anti-VIII immunoglobulin isolated from various bleedings were identified by use of rabbit anti-equine heavy chain specific reagents. Radioimmunodiffusion with 14C-labelled type XXV pneumococcal capsular polysaccharide and horse and donkey reagents with species specificity directed against donkey or horse IgGa respectively, demonstrated both parental horse and donkey IgGa heavy chain isotypes among the anti-PnXXV antibodies of the interspecies hybrid. Qualtitative and quantitative examination of the cross-precipitation of mule anti-PnXXV sera with the capsular polysaccharides of pneumococcal types IV, X and XA, with birch sap, ketha gum, and with polysaccharides of E. coli, Klebsiella and Rhizobium was carried out and compared with data obtained with anti-PnXXV raised in a horse. Analysis of supernatants from the cross-reactions showed that distinct subfractions had reacted. indicating a marked heterogeneity of the antibodies."}
{"id": "PMID:28293", "title": "Ionic binding of aminoglycosides to human serum albumin in the absence of divalent cations. IV. Effect of structure, ph and concentration.", "content": "The binding of sisomicin and streptomycin to human serum albumin was studied in the absence of divalent cations by means of the dialysis method. Hydrophobic bonds between albumin and sisomicin or streptomycin can be excluded by nuclear magnetic resonance measurements. The presence of hydrogen bonds is made unlikely according to the result that the binding of the aminoglycosides decreases with increasing number of OH groups in the aminoglycoside molecule. The pH dependence of protein binding suggests that ionic bonds are involved in the binding of aminoglycosides. On the basis of the concentration dependence of the albumin binding of sisomicin and streptomycin we determined the binding affinities delta F degrees, the binding constants K1, and the maximum number n of aminoglycoside molecules that can be bound by a molecule of albumin in the absence of Ca++ ions. The results were as follows: Sisomicin: delta F degrees = -4189 cal/mole, K1 = 900 1/mole, n = 12; Streptomycin: delta F degrees = 3512 cal/mole, K1 = 300 1/mole, n = 17.", "contents": "Ionic binding of aminoglycosides to human serum albumin in the absence of divalent cations. IV. Effect of structure, ph and concentration. The binding of sisomicin and streptomycin to human serum albumin was studied in the absence of divalent cations by means of the dialysis method. Hydrophobic bonds between albumin and sisomicin or streptomycin can be excluded by nuclear magnetic resonance measurements. The presence of hydrogen bonds is made unlikely according to the result that the binding of the aminoglycosides decreases with increasing number of OH groups in the aminoglycoside molecule. The pH dependence of protein binding suggests that ionic bonds are involved in the binding of aminoglycosides. On the basis of the concentration dependence of the albumin binding of sisomicin and streptomycin we determined the binding affinities delta F degrees, the binding constants K1, and the maximum number n of aminoglycoside molecules that can be bound by a molecule of albumin in the absence of Ca++ ions. The results were as follows: Sisomicin: delta F degrees = -4189 cal/mole, K1 = 900 1/mole, n = 12; Streptomycin: delta F degrees = 3512 cal/mole, K1 = 300 1/mole, n = 17."}
{"id": "PMID:28288", "title": "Factors affecting in vitro lipid peroxidation of rat brain homogenate.", "content": "Peroxidation of the unsaturated lipid of tissue homogenates is an established method to assess the antioxidant or vitamin E status of animals. In the present study the spontaneous lipid peroxidation in air of rat brain homogenates is reported. The effects of various factors like pH, time, concentration of tissues, temperature, ferrocompounds and catalysis by added tissues like liver are described. Rat brain homogenates appear to be a suitable preparation for in vitro studies of lipid peroxidation.", "contents": "Factors affecting in vitro lipid peroxidation of rat brain homogenate. Peroxidation of the unsaturated lipid of tissue homogenates is an established method to assess the antioxidant or vitamin E status of animals. In the present study the spontaneous lipid peroxidation in air of rat brain homogenates is reported. The effects of various factors like pH, time, concentration of tissues, temperature, ferrocompounds and catalysis by added tissues like liver are described. Rat brain homogenates appear to be a suitable preparation for in vitro studies of lipid peroxidation."}
{"id": "PMID:28289", "title": "Enhancement of insulin hypoglycaemia by beta adrenoceptor antagonists.", "content": "Interaction of insulin with beta-adrenoceptor antagonists was studied in conscious rabbits. Propranolol and metoprolol did not modify the peak of insulin hypoglycaemia but delayed its recovery. Practolol, sotalol and 1-INPEA enhanced the peak effect and delayed the recovery of insulin-induced hypoglycaemia. H 35/25 and d-INPEA did not modify insulin hypoglycaemia. The beta-blockers did not produce significant hypoglycaemia per se. Since sotalol, 1-INPEA (specific beta-adrenoceptor antagonists devoid of local anaesthetic activity); practolol and metoprolol (selective cardiac beta-1 adrenoceptor antagonists) enhanced hypoglycaemic action of insulin and H 35/25 (a selective beta-2 adrenoceptor antagonist) failed to affect it, it seems that selective beta-adrenoceptor blockade (similar to cardiac beta-1 adrenoceptors) mediates enhancement of insulin hypoglycaemia. Caution should, therefore, be exercised in administering beta-adrenoceptor antagonists and insulin together. A reduction in the dose of insulin may be necessary.", "contents": "Enhancement of insulin hypoglycaemia by beta adrenoceptor antagonists. Interaction of insulin with beta-adrenoceptor antagonists was studied in conscious rabbits. Propranolol and metoprolol did not modify the peak of insulin hypoglycaemia but delayed its recovery. Practolol, sotalol and 1-INPEA enhanced the peak effect and delayed the recovery of insulin-induced hypoglycaemia. H 35/25 and d-INPEA did not modify insulin hypoglycaemia. The beta-blockers did not produce significant hypoglycaemia per se. Since sotalol, 1-INPEA (specific beta-adrenoceptor antagonists devoid of local anaesthetic activity); practolol and metoprolol (selective cardiac beta-1 adrenoceptor antagonists) enhanced hypoglycaemic action of insulin and H 35/25 (a selective beta-2 adrenoceptor antagonist) failed to affect it, it seems that selective beta-adrenoceptor blockade (similar to cardiac beta-1 adrenoceptors) mediates enhancement of insulin hypoglycaemia. Caution should, therefore, be exercised in administering beta-adrenoceptor antagonists and insulin together. A reduction in the dose of insulin may be necessary."}
{"id": "PMID:28290", "title": "Acetylcholine: a possible neurotransmitter in Setaria cervi.", "content": "The total and free acetylcholine (Ach) and cholinesterase (CHE) content of adult Setaria cervi were estimated. The Ach was estimated by bioassay on rectus abdominis muscle of frog and the CHE by measuring the drop in pH following incubation of worm homogenate with Ach chloride. The free and total Ach contents (4.0 +/- 0.57 and 6.0 +/- 0.48 microgram/g wet weight of worms respectively) were as high as found in mammalian brain cortex. The cholinesterase activity was found to be 5.57 +/- 0.6 units/g wet weight of worms. It is possible that there may exist a well developed system responsible for the synthesis, storage, release and destruction of Ach and that Ach may be acting as an excitatory neurohormone in S. cervi.", "contents": "Acetylcholine: a possible neurotransmitter in Setaria cervi. The total and free acetylcholine (Ach) and cholinesterase (CHE) content of adult Setaria cervi were estimated. The Ach was estimated by bioassay on rectus abdominis muscle of frog and the CHE by measuring the drop in pH following incubation of worm homogenate with Ach chloride. The free and total Ach contents (4.0 +/- 0.57 and 6.0 +/- 0.48 microgram/g wet weight of worms respectively) were as high as found in mammalian brain cortex. The cholinesterase activity was found to be 5.57 +/- 0.6 units/g wet weight of worms. It is possible that there may exist a well developed system responsible for the synthesis, storage, release and destruction of Ach and that Ach may be acting as an excitatory neurohormone in S. cervi."}
{"id": "PMID:28295", "title": "Inhibition of allergic reactions by a new antiallergic drug, LC-6 (trans-2,3b,4,5,7,8b,9,10-octahydronaphthol[1,2-c:5,6-c'] dipyrazole). I. Inhibition of the rat reaginic passive cutaneous anaphylaxis.", "content": "A new synthetic compound, LC-6, has been shown to inhibit the passive cutaneous anaphylaxis reactions induced in rats by mouse reaginic antibody. In this system, the ED50 was 35 mg/kg body weight of LC-6 administered per os. LC-6 prevented neither histamine skin reactions nor the reactions to histamine and other chemical mediators released by 48/80. Therefore, its inhibitory activity is comparable to that of the model anti-allergic compound, disodium cromoglycate (DSCG). In contrast to DSCG, the new drug exhibits the distinct advantage of being active per os and over prolonged periods of time. Its activity has been shown to persist for at least 6 h when doses 4 times higher than the ED50 were administered. The duration of the drug effect was clearly dose-dependent. Predoses of the compound increased its effectiveness. The long-lasting association of LC-6 with mast cells, as indicated by its prolonged inhibitory activity, makes it a valuable tool in the search for receptors involved in anaphylactic reactions.", "contents": "Inhibition of allergic reactions by a new antiallergic drug, LC-6 (trans-2,3b,4,5,7,8b,9,10-octahydronaphthol[1,2-c:5,6-c'] dipyrazole). I. Inhibition of the rat reaginic passive cutaneous anaphylaxis. A new synthetic compound, LC-6, has been shown to inhibit the passive cutaneous anaphylaxis reactions induced in rats by mouse reaginic antibody. In this system, the ED50 was 35 mg/kg body weight of LC-6 administered per os. LC-6 prevented neither histamine skin reactions nor the reactions to histamine and other chemical mediators released by 48/80. Therefore, its inhibitory activity is comparable to that of the model anti-allergic compound, disodium cromoglycate (DSCG). In contrast to DSCG, the new drug exhibits the distinct advantage of being active per os and over prolonged periods of time. Its activity has been shown to persist for at least 6 h when doses 4 times higher than the ED50 were administered. The duration of the drug effect was clearly dose-dependent. Predoses of the compound increased its effectiveness. The long-lasting association of LC-6 with mast cells, as indicated by its prolonged inhibitory activity, makes it a valuable tool in the search for receptors involved in anaphylactic reactions."}
{"id": "PMID:28291", "title": "Effect of light and exhaustive ergometric exercise on blood sugar, total cholesterol and pH in untrained young human subjects.", "content": "Light and exhaustive ergometric exercise in untrained male and female medical students in the age group 18-21 years resulted in significant lowering of the blood sugar, cholesterol and pH. Females exhibited hypoglycemia of slightly greater magnitude as compared to male subjects and during both the exercises, however, such sex differences were not observed for changes in cholesterol and pH.", "contents": "Effect of light and exhaustive ergometric exercise on blood sugar, total cholesterol and pH in untrained young human subjects. Light and exhaustive ergometric exercise in untrained male and female medical students in the age group 18-21 years resulted in significant lowering of the blood sugar, cholesterol and pH. Females exhibited hypoglycemia of slightly greater magnitude as compared to male subjects and during both the exercises, however, such sex differences were not observed for changes in cholesterol and pH."}
{"id": "PMID:28296", "title": "Immunological nature of the inhibition of BLV-induced early polykaryocytosis by bovine sera.", "content": "A quantitative in vitro assay (EPI) was developed for the serological detection of bovine leukemia virus (BLV) infection in cattle. Positive sera inhibit early polykaryocytosis (EP) induced by BLV. We report herein experiments which demonstrate that BLV-induced antibodies are responsible for this inhibition. Serum fractionation by gel filtration and affinity chromatography indicate that EP-inhibiting activity is mediated only by immunoglobulins of the IgG class. Furthermore, on the basis of their ion-exchange chromatographic behaviour, these antibodies were classified as IgG1. We also ruled out the participation in the EP inhibition reaction of the other compounds such as polypeptides, including serum complement and interferon or DNA and RNA. These results demonstrate that EP inhibition by bovine sera is specific to BLV-induced antibodies.", "contents": "Immunological nature of the inhibition of BLV-induced early polykaryocytosis by bovine sera. A quantitative in vitro assay (EPI) was developed for the serological detection of bovine leukemia virus (BLV) infection in cattle. Positive sera inhibit early polykaryocytosis (EP) induced by BLV. We report herein experiments which demonstrate that BLV-induced antibodies are responsible for this inhibition. Serum fractionation by gel filtration and affinity chromatography indicate that EP-inhibiting activity is mediated only by immunoglobulins of the IgG class. Furthermore, on the basis of their ion-exchange chromatographic behaviour, these antibodies were classified as IgG1. We also ruled out the participation in the EP inhibition reaction of the other compounds such as polypeptides, including serum complement and interferon or DNA and RNA. These results demonstrate that EP inhibition by bovine sera is specific to BLV-induced antibodies."}
{"id": "PMID:28297", "title": "The dissociation of b-TSH. The effect of sodium dodecyl sulfate, pH, urea and temperature.", "content": "In the present study SDS polyacrylamide gel electrophoresis was used to reinvestigate the conditions under which b-TSH dissociates into its constituent subunits. The effects of SDS, itself, urea, acid pH and temperature were assessed by the decrease in the amount of undissociated TSH and the increase in the dissociated components as revealed by SDS gel electrophoresis. In SDS alone 25--30% dissociation occurred. Pre-treatment with increasing concentrations of urea up to 7.1 M increased the degree of dissociation to 70% after h at room temperature. Maximum dissociation was achieved by treatment at pH 2.5 and 37 degree C for 1 h. In 1 M propionic acid approximately 10% of the TSH was still undissociated after 18 h at 25 degree C.", "contents": "The dissociation of b-TSH. The effect of sodium dodecyl sulfate, pH, urea and temperature. In the present study SDS polyacrylamide gel electrophoresis was used to reinvestigate the conditions under which b-TSH dissociates into its constituent subunits. The effects of SDS, itself, urea, acid pH and temperature were assessed by the decrease in the amount of undissociated TSH and the increase in the dissociated components as revealed by SDS gel electrophoresis. In SDS alone 25--30% dissociation occurred. Pre-treatment with increasing concentrations of urea up to 7.1 M increased the degree of dissociation to 70% after h at room temperature. Maximum dissociation was achieved by treatment at pH 2.5 and 37 degree C for 1 h. In 1 M propionic acid approximately 10% of the TSH was still undissociated after 18 h at 25 degree C."}
{"id": "PMID:28300", "title": "Assessment of long-acting neuroleptics. Methods and problems.", "content": "Long-acting neuroleptics, without offering a therapeutic breakthrough in the treatment of schizophrenia, are nevertheless a definite step in the management of patients with this disorder. The adequate assessment of these agents necessitates methodological considerations to ensure first, just and adequate patient selection, secondly, adaptations to the drug's characteristics, thridly, sufficient duration of the study and finally, special precautions in the assessment of toxicity. Furthermore, the patient management in these studies must ensure continued and easy accessibility of the simultaneously investigating and treating team.", "contents": "Assessment of long-acting neuroleptics. Methods and problems. Long-acting neuroleptics, without offering a therapeutic breakthrough in the treatment of schizophrenia, are nevertheless a definite step in the management of patients with this disorder. The adequate assessment of these agents necessitates methodological considerations to ensure first, just and adequate patient selection, secondly, adaptations to the drug's characteristics, thridly, sufficient duration of the study and finally, special precautions in the assessment of toxicity. Furthermore, the patient management in these studies must ensure continued and easy accessibility of the simultaneously investigating and treating team."}
{"id": "PMID:28301", "title": "The pH dependency of sodium and chloride transport in the isolated human cornea.", "content": "Sodium and chloride net transport in isolated human cornea preparations were found to be pH dependent. Sodium net transport was directed from aqueous humor to tear side at pH 7.6 and 8.6. At pH 7.4, net sodium flux did not differ significantly from zero, and at pH 7.0, net sodium transport was directed toward the aqueous humor side. Chloride net flux at pH 8.6 and 7.6 was also directed from aqueous humor to tear side. Acidification of the bathing solution to pH 7.4 and 7.0 was followed by a decrease in chloride net fluxes to values not significantly different from zero.", "contents": "The pH dependency of sodium and chloride transport in the isolated human cornea. Sodium and chloride net transport in isolated human cornea preparations were found to be pH dependent. Sodium net transport was directed from aqueous humor to tear side at pH 7.6 and 8.6. At pH 7.4, net sodium flux did not differ significantly from zero, and at pH 7.0, net sodium transport was directed toward the aqueous humor side. Chloride net flux at pH 8.6 and 7.6 was also directed from aqueous humor to tear side. Acidification of the bathing solution to pH 7.4 and 7.0 was followed by a decrease in chloride net fluxes to values not significantly different from zero."}
{"id": "PMID:28307", "title": "Variability of oxygen affinity of normal blood: an automated method of measurement.", "content": "Oxygen equilibrium curves of 48 healthy adult subjects have been measured by the method of Rossi-Bernardi et al. (Clin. Chem. 21: 1747, 1975), in which H2O2 is gradually added to a sample of deoxygenated blood that contains an excess of catalase. The mean P50 for nonsmokers was 26.9 Torr and the distribution of values was slightly skewed to the right (range 24.2--29.9 Torr). The method differs from others previously available in that pH, PCO2, and HCO3-- are constant during oxygenation. The system for control of the experiment and data collection and processing has been automated by the use of a microprocessor so that the equilibrium curve can be obtained quickly, reproducibly, and relatively simply. With the aid of a digital computer, the parameters of the generalized Adair equation can also be estimated.", "contents": "Variability of oxygen affinity of normal blood: an automated method of measurement. Oxygen equilibrium curves of 48 healthy adult subjects have been measured by the method of Rossi-Bernardi et al. (Clin. Chem. 21: 1747, 1975), in which H2O2 is gradually added to a sample of deoxygenated blood that contains an excess of catalase. The mean P50 for nonsmokers was 26.9 Torr and the distribution of values was slightly skewed to the right (range 24.2--29.9 Torr). The method differs from others previously available in that pH, PCO2, and HCO3-- are constant during oxygenation. The system for control of the experiment and data collection and processing has been automated by the use of a microprocessor so that the equilibrium curve can be obtained quickly, reproducibly, and relatively simply. With the aid of a digital computer, the parameters of the generalized Adair equation can also be estimated."}
{"id": "PMID:28308", "title": "Alpha-adrenergic receptors in human and canine tracheal and bronchial smooth muscle.", "content": "We studied the reactions of human tracheal and bronchial smooth muscle and canine trachealis muscle to adrenergic agonists. Human tissue was obtained from recent autopsies of patients with normal lungs and patients with respiratory disorders, and canine tissue was obtained from animals used in other experiments. The muscle was mounted in tissue baths fitted with platinum wire electrodes and the mechanical activity was recorded. Norepinephrine added to the normal human or canine tissue in concentrations up to 10(-5) M caused no reaction. In the normal human and in the dog, pretreatment with histamine or KCl changed this response and when norepinephrine was added the tissue contracted. This contraction was blocked by phentolamine or N,N'-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC). In diseased tissue, the addition of norepinephrine resulted in a contraction that was blocked by phentolamine or BHC and no pretreatment with histamine or KCl was required. These findings demonstrate alpha-receptors in human and canine airway smooth muscle, and there is a difference between normal and diseased human tissue in the reaction of these tissues to alpha-adrenergic agonists.", "contents": "Alpha-adrenergic receptors in human and canine tracheal and bronchial smooth muscle. We studied the reactions of human tracheal and bronchial smooth muscle and canine trachealis muscle to adrenergic agonists. Human tissue was obtained from recent autopsies of patients with normal lungs and patients with respiratory disorders, and canine tissue was obtained from animals used in other experiments. The muscle was mounted in tissue baths fitted with platinum wire electrodes and the mechanical activity was recorded. Norepinephrine added to the normal human or canine tissue in concentrations up to 10(-5) M caused no reaction. In the normal human and in the dog, pretreatment with histamine or KCl changed this response and when norepinephrine was added the tissue contracted. This contraction was blocked by phentolamine or N,N'-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC). In diseased tissue, the addition of norepinephrine resulted in a contraction that was blocked by phentolamine or BHC and no pretreatment with histamine or KCl was required. These findings demonstrate alpha-receptors in human and canine airway smooth muscle, and there is a difference between normal and diseased human tissue in the reaction of these tissues to alpha-adrenergic agonists."}
{"id": "PMID:28309", "title": "Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation.", "content": "The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration. Rapamycin cured systemic candidosis in mice: PD50 s.c. was 9.5 mg/kg: PD50 p.o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment.", "contents": "Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation. The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration. Rapamycin cured systemic candidosis in mice: PD50 s.c. was 9.5 mg/kg: PD50 p.o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment."}
{"id": "PMID:28310", "title": "Specificity and regulation of gamma-aminobutyrate transport in Escherichia coli.", "content": "A specific gamma-aminobutyrate (GABA) transport system in Escherichia coli K-12 cells with a K(m) of 12 muM and a V(max) of 278 nmol/ml of intracellular water per min is described. Membrane vesicles contained d-lactate-dependent activity of the system. Mutants defective in GABA transport were isolated; they lost the ability to utilize GABA as a nitrogen source, although the activities of glutamate-succinylsemialdehyde transaminase (GSST) (EC 2.6.1.19) and succinylsemialdehyde dehydrogenase (SSDH) (EC 1.2.1.16), the enzymes that catalyze GABA utilization, remained as high as in the parental CS101B strain. The ability to utilize l-ornithine, l-arginine, putrescine, l-proline, and glycine as a nitrogen source was preserved in the mutants. The genetic lesions resulting in the loss of GABA transport, gabP5 and gabP9, mapped in the gab gene cluster in close linkage to gabT and gabD, the structural genes of GSST and SSDH, and to gabC, a gene controlling the utilization of GABA, arginine, putrescine, and ornithine. The synthesis of the GABA transport carrier is subject to dual physiological control by (i) catabolite repression and (ii) nitrogen availability. Experiments with glutamine synthetase (EC 6.3.1.2)-negative and with glutamine synthetase-constitutive strains strongly indicate that this enzyme is the effector in the regulation of GABA carrier synthesis by route (ii).", "contents": "Specificity and regulation of gamma-aminobutyrate transport in Escherichia coli. A specific gamma-aminobutyrate (GABA) transport system in Escherichia coli K-12 cells with a K(m) of 12 muM and a V(max) of 278 nmol/ml of intracellular water per min is described. Membrane vesicles contained d-lactate-dependent activity of the system. Mutants defective in GABA transport were isolated; they lost the ability to utilize GABA as a nitrogen source, although the activities of glutamate-succinylsemialdehyde transaminase (GSST) (EC 2.6.1.19) and succinylsemialdehyde dehydrogenase (SSDH) (EC 1.2.1.16), the enzymes that catalyze GABA utilization, remained as high as in the parental CS101B strain. The ability to utilize l-ornithine, l-arginine, putrescine, l-proline, and glycine as a nitrogen source was preserved in the mutants. The genetic lesions resulting in the loss of GABA transport, gabP5 and gabP9, mapped in the gab gene cluster in close linkage to gabT and gabD, the structural genes of GSST and SSDH, and to gabC, a gene controlling the utilization of GABA, arginine, putrescine, and ornithine. The synthesis of the GABA transport carrier is subject to dual physiological control by (i) catabolite repression and (ii) nitrogen availability. Experiments with glutamine synthetase (EC 6.3.1.2)-negative and with glutamine synthetase-constitutive strains strongly indicate that this enzyme is the effector in the regulation of GABA carrier synthesis by route (ii)."}
{"id": "PMID:28311", "title": "Structural basis of the thermostability of monomeric malate synthase from a thermophilic Bacillus.", "content": "Malate synthases from a thermophilic Bacillus and Escherichia coli have been isolated in a high state of purity. Molecular weights of these two proteins determined in the native state and after denaturation in sodium dodecyl sulfate-mercaptoethanol show that the enzymes are monomeric. This conclusion is supported, for the thermophile enzyme, by the result of an electrophoretic analysis of that protein after treatment with dimethylsuberimidate and denaturation. The thermophilic Bacillus malate synthase is considerably more thermostable than its mesophilic counterparts from E. coli, Bacillus licheniformis, and Pseudomonas indigofera. It is, however, markedly labilized by an increase in the ionic strength of the medium brought about by the addition of 0.2 M potassium chloride or in pH above 9. Increased ionic strength has little effect on the thermostability of the mesophilic bacterial malate synthases. These observations provide strong support for the idea that monomeric proteins in thermophiles owe their unusual heat stability to the presence of salt bridges in their tertiary structure.", "contents": "Structural basis of the thermostability of monomeric malate synthase from a thermophilic Bacillus. Malate synthases from a thermophilic Bacillus and Escherichia coli have been isolated in a high state of purity. Molecular weights of these two proteins determined in the native state and after denaturation in sodium dodecyl sulfate-mercaptoethanol show that the enzymes are monomeric. This conclusion is supported, for the thermophile enzyme, by the result of an electrophoretic analysis of that protein after treatment with dimethylsuberimidate and denaturation. The thermophilic Bacillus malate synthase is considerably more thermostable than its mesophilic counterparts from E. coli, Bacillus licheniformis, and Pseudomonas indigofera. It is, however, markedly labilized by an increase in the ionic strength of the medium brought about by the addition of 0.2 M potassium chloride or in pH above 9. Increased ionic strength has little effect on the thermostability of the mesophilic bacterial malate synthases. These observations provide strong support for the idea that monomeric proteins in thermophiles owe their unusual heat stability to the presence of salt bridges in their tertiary structure."}
{"id": "PMID:28312", "title": "High-dose benzodiazepines in the treatment of severe neurotic anxiety.", "content": "There has been a paucity of research in the use of high-dose benzodiazepines in the treatment of severe neurotic anxiety. The author presents five cases, three with excellent and two with poor outcomes. The English and Fench language literature is reviewed and reveals evidence that high-dose benzodiazepines may be useful in the treatment of certain neurotic patients. However, the lack of controlled studies is noted. The author poses several questions important to the future of research on benzodiazepines.", "contents": "High-dose benzodiazepines in the treatment of severe neurotic anxiety. There has been a paucity of research in the use of high-dose benzodiazepines in the treatment of severe neurotic anxiety. The author presents five cases, three with excellent and two with poor outcomes. The English and Fench language literature is reviewed and reveals evidence that high-dose benzodiazepines may be useful in the treatment of certain neurotic patients. However, the lack of controlled studies is noted. The author poses several questions important to the future of research on benzodiazepines."}
{"id": "PMID:28313", "title": "Multi-clinic double-blind comparison of triazolam (Halcion) and placebo administered for 14 consecutive nights in outpatients with insomnia.", "content": "In this multi-clinic double-blind study, patients suffering from insomnia were treated with triazolam 0.5 mg (Halcion) or placebo for 14 days. Four investigators treated 239 patients, 122 on triazolam and 117 on placebo. Thirty-nine patients, 10 on triazolam and 29 on placebo, dropped out for ineffectiveness of the medication and 32 patients, 16 in each group, dropped out for side effects. Analysis of pooled efficacy data showed that triazolam was significantly better than placebo on all efficacy parameters measured, including how much the medication helped the patients sleep, onset of sleep, duration of sleep, duration compared to usual, number of nocturnal awakenings, and feeling of restfulness in the morning. Triazolam did not produce evidence of tolerance development after 2 weeks of treatment. The same variety of side effects occurred on each treatment and primarily included drowsiness, grogginess, headaches, impaired coordination nausea, and dizziness.", "contents": "Multi-clinic double-blind comparison of triazolam (Halcion) and placebo administered for 14 consecutive nights in outpatients with insomnia. In this multi-clinic double-blind study, patients suffering from insomnia were treated with triazolam 0.5 mg (Halcion) or placebo for 14 days. Four investigators treated 239 patients, 122 on triazolam and 117 on placebo. Thirty-nine patients, 10 on triazolam and 29 on placebo, dropped out for ineffectiveness of the medication and 32 patients, 16 in each group, dropped out for side effects. Analysis of pooled efficacy data showed that triazolam was significantly better than placebo on all efficacy parameters measured, including how much the medication helped the patients sleep, onset of sleep, duration of sleep, duration compared to usual, number of nocturnal awakenings, and feeling of restfulness in the morning. Triazolam did not produce evidence of tolerance development after 2 weeks of treatment. The same variety of side effects occurred on each treatment and primarily included drowsiness, grogginess, headaches, impaired coordination nausea, and dizziness."}
{"id": "PMID:28314", "title": "A microelectronic pH sensor.", "content": "This paper presents preliminary data on a new integrated circuit microelectronic pH sensor. The device is extremely miniaturized by the use of integrated circuit technology, and uses the intrinsic hydrogen ion selective properties of the gate insulator material. In order to make the device compatible with aqueous solution monitoring, the silicon dioxide-silicon nitride gate insulator structure is used. The integrated circuit chip was designed, processed, and packaged by a variety of techniques which protect all metal parts from the aqueous solution. Test data are reported on leakage current, sensitivity, reproducibility, linearity, stability, response time, and life. The results indicate that this type of pH sensor may have many significant advantages for biomedical research and application.", "contents": "A microelectronic pH sensor. This paper presents preliminary data on a new integrated circuit microelectronic pH sensor. The device is extremely miniaturized by the use of integrated circuit technology, and uses the intrinsic hydrogen ion selective properties of the gate insulator material. In order to make the device compatible with aqueous solution monitoring, the silicon dioxide-silicon nitride gate insulator structure is used. The integrated circuit chip was designed, processed, and packaged by a variety of techniques which protect all metal parts from the aqueous solution. Test data are reported on leakage current, sensitivity, reproducibility, linearity, stability, response time, and life. The results indicate that this type of pH sensor may have many significant advantages for biomedical research and application."}
{"id": "PMID:28315", "title": "Fabrication of pH-sensitive implantable electrode by thick film hybrid technology.", "content": "We report preliminary results of our experiments directed at fabricating pH-sensitive electrodes suitable for in vivo use by means of thick film screening techniques. Our results show that glass membranes of suitable thickness and possessing nearly theoretical sensitivity to pH can be fabricated by this process. A hybrid electrode structure permits the incorporation of a source follower FET amplifier directly adjacent to the pH membrane, significantly reducing response time and noise pick-up. Extension of the basic electrode structure to accommodate membranes sensitive to other ions is discussed.", "contents": "Fabrication of pH-sensitive implantable electrode by thick film hybrid technology. We report preliminary results of our experiments directed at fabricating pH-sensitive electrodes suitable for in vivo use by means of thick film screening techniques. Our results show that glass membranes of suitable thickness and possessing nearly theoretical sensitivity to pH can be fabricated by this process. A hybrid electrode structure permits the incorporation of a source follower FET amplifier directly adjacent to the pH membrane, significantly reducing response time and noise pick-up. Extension of the basic electrode structure to accommodate membranes sensitive to other ions is discussed."}
{"id": "PMID:28317", "title": "Use of enzymolysis techniques in studying the mechanical properties of connective tissue components.", "content": "The optimum conditions for the selective removal of elastin from connective tissues are described. The process, elastolysis, consists of incubating small samples of connective tissue in buffered saline at ph=8.6 containing 300 microgram/me of a 50-50% mixture of elastase with trypsin inhibitor, for 5-6 hours at room temperature. This process, complimented with other processes for selective removal of lipids, or mucopolysaccharides, or collagen, enables one to examine the contribution of the various components of the connective tissue to its mechanical function. The elastolysis was tested with aortic, valvular and tendon tissues from human, bovine and canine species and it was found that in tensile stress experiments, collagen was unaffected while the low-stress contribution of elastin disappeared.", "contents": "Use of enzymolysis techniques in studying the mechanical properties of connective tissue components. The optimum conditions for the selective removal of elastin from connective tissues are described. The process, elastolysis, consists of incubating small samples of connective tissue in buffered saline at ph=8.6 containing 300 microgram/me of a 50-50% mixture of elastase with trypsin inhibitor, for 5-6 hours at room temperature. This process, complimented with other processes for selective removal of lipids, or mucopolysaccharides, or collagen, enables one to examine the contribution of the various components of the connective tissue to its mechanical function. The elastolysis was tested with aortic, valvular and tendon tissues from human, bovine and canine species and it was found that in tensile stress experiments, collagen was unaffected while the low-stress contribution of elastin disappeared."}
{"id": "PMID:28318", "title": "Diffusion of fluoride ions in dental enamel at pH 7.", "content": "The penetration and uptake of both radioactive (18F) and stable fluoride (19F) in bovine enamel were investigated. Buffered pH 7 NaF solutions were employed. Penetration profiles of both 18F and 19F in enamel were determined by using a sectioning technique. 18F and 19F concentrations decreased exponentially with increasing penetration distance. The uptake of 18F in enamel can be described by a power function of the immersion time, with an average power of 0.76. The results agree reasonably with our previously published theoretical model for the diffusion in enamel, based on simultaneous diffusion in enamel pores and in the hydroxyapatite crystallites. The diffusion coefficients of fluoride ions in enamel obtained from the application of the model to the results presented here, were: D = 0.9 x 10(-17) cm2/s in the crystallites and D' = 3.3 x 10(-10) cm2/s in the enamel pores. An average penetration depth of fluoride ions at pH 7.0 of 8 micron in 4 hours has been calculated.", "contents": "Diffusion of fluoride ions in dental enamel at pH 7. The penetration and uptake of both radioactive (18F) and stable fluoride (19F) in bovine enamel were investigated. Buffered pH 7 NaF solutions were employed. Penetration profiles of both 18F and 19F in enamel were determined by using a sectioning technique. 18F and 19F concentrations decreased exponentially with increasing penetration distance. The uptake of 18F in enamel can be described by a power function of the immersion time, with an average power of 0.76. The results agree reasonably with our previously published theoretical model for the diffusion in enamel, based on simultaneous diffusion in enamel pores and in the hydroxyapatite crystallites. The diffusion coefficients of fluoride ions in enamel obtained from the application of the model to the results presented here, were: D = 0.9 x 10(-17) cm2/s in the crystallites and D' = 3.3 x 10(-10) cm2/s in the enamel pores. An average penetration depth of fluoride ions at pH 7.0 of 8 micron in 4 hours has been calculated."}
{"id": "PMID:28319", "title": "Characterization of ionomycin as a calcium ionophore.", "content": "The ionophorous properties of a new antibiotic, ionomycin, have been studied. It was found that the antibiotic is capable of extracting calcium ion from the bulk of an aqueous phase into an organic phase. The antibiotic also acts as a mobile ion carrier to transport the cation across a solvent barrier. The divalent cation selectivity order for ionomycin as determined by ion competition experiments was found to be: Ca greater than Mg greater than Sr = Ba, where the binding of strontium and barium by the antibiotic is insignificant. The antibiotic also binds La3+ to some extent, but its complexation with monovalent alkali metal ions is negligible. Measurement of the binding of ionomycin with Ca2+ indicates that ionomycin complexes and transports calcium ion in a one to one stoichiometry.", "contents": "Characterization of ionomycin as a calcium ionophore. The ionophorous properties of a new antibiotic, ionomycin, have been studied. It was found that the antibiotic is capable of extracting calcium ion from the bulk of an aqueous phase into an organic phase. The antibiotic also acts as a mobile ion carrier to transport the cation across a solvent barrier. The divalent cation selectivity order for ionomycin as determined by ion competition experiments was found to be: Ca greater than Mg greater than Sr = Ba, where the binding of strontium and barium by the antibiotic is insignificant. The antibiotic also binds La3+ to some extent, but its complexation with monovalent alkali metal ions is negligible. Measurement of the binding of ionomycin with Ca2+ indicates that ionomycin complexes and transports calcium ion in a one to one stoichiometry."}
{"id": "PMID:28320", "title": "Evidence for thyroid hormone-dependent and independent glucocorticoid actions in cultured cells. Studies on the induction of growth hormone and glutamine synthetase in GH1 cells and tyrosine aminotransferase in Reuber H-35 cells.", "content": "The induction of growth hormone synthesis and mRNA by thyroid hormone in cultured GH1 cells is mediated by the thyroid hormone nuclear receptor. In addition, the regulation of the growth hormone response by glucocorticoid is highly dependent on the action of thyroid hormone. To clarify whether thyroid hormone has a general influence on glucocorticoid action in GH1 cells, the glucocorticoid induction of growth hormone and glutamine synthetase was simultaneously examined. In contrast to the growth hormone response, the induction of glutamine synthetase by glucocorticoid was not influenced by thyroid hormone. Both responses appear to be modulated by the glucocorticoid receptor, and thyroid hormone had no influence on nuclear-associated glucocorticoid receptor levels. These results suggest that the thyroid hormone control of glucocorticoid induction of growth hormone may be a selective process, and the nuclear associated receptors for both thyroid and glucocorticoid hormones interrelate to control the growth hormone response.", "contents": "Evidence for thyroid hormone-dependent and independent glucocorticoid actions in cultured cells. Studies on the induction of growth hormone and glutamine synthetase in GH1 cells and tyrosine aminotransferase in Reuber H-35 cells. The induction of growth hormone synthesis and mRNA by thyroid hormone in cultured GH1 cells is mediated by the thyroid hormone nuclear receptor. In addition, the regulation of the growth hormone response by glucocorticoid is highly dependent on the action of thyroid hormone. To clarify whether thyroid hormone has a general influence on glucocorticoid action in GH1 cells, the glucocorticoid induction of growth hormone and glutamine synthetase was simultaneously examined. In contrast to the growth hormone response, the induction of glutamine synthetase by glucocorticoid was not influenced by thyroid hormone. Both responses appear to be modulated by the glucocorticoid receptor, and thyroid hormone had no influence on nuclear-associated glucocorticoid receptor levels. These results suggest that the thyroid hormone control of glucocorticoid induction of growth hormone may be a selective process, and the nuclear associated receptors for both thyroid and glucocorticoid hormones interrelate to control the growth hormone response."}
{"id": "PMID:28321", "title": "Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney.", "content": "Prolylcarboxypeptidase was purified from human kidney 1200-fold with 18% yield. The enzyme had no cathepsin A activity and appeared to be homogeneous in gel electrophoresis. The molecular weight of prolylcarboxypeptidase was estimated to be 115,000 by gel filtration. Under denaturing conditions the enzyme dissociated into subunits of 45,000 and 66,500 molecular weight. The enzyme cleaved benzyloxycarbonyl (Cbz)-Pro-Phe, representing the COOH-terminal end of angiotensin II and des-Asp1-angiotensin II (angiotensin III), at a rate of 31 micronmol/h/mg of protein. The rate of hydrolysis increased when phenylalanine in the N-protected dipeptide was replaced with alanine, valine, or leucine or when the octapeptide angiotensin II or the heptapeptide angiotensin III were the substrates. The enzyme also cleaved the angiotensin II antagonist saralasin (Sar1-Ala8-angiotensin II). The Km values were 1 mM, 2mM, and 0.77 mM with Cbz-Pro-Phe, angiotensin II, and angiotensin III, respectively. The enzyme had an acid pH optimum (4.5 to 5.5), but hydrolyzed angiotensin III at pH 7 at 50% of the optimal rate. Prolylcarboxypeptidase was inhibited by diisopropyl phosphorofluoridate and pepstatin, but not by sequestering agents or -SH reagents.", "contents": "Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney. Prolylcarboxypeptidase was purified from human kidney 1200-fold with 18% yield. The enzyme had no cathepsin A activity and appeared to be homogeneous in gel electrophoresis. The molecular weight of prolylcarboxypeptidase was estimated to be 115,000 by gel filtration. Under denaturing conditions the enzyme dissociated into subunits of 45,000 and 66,500 molecular weight. The enzyme cleaved benzyloxycarbonyl (Cbz)-Pro-Phe, representing the COOH-terminal end of angiotensin II and des-Asp1-angiotensin II (angiotensin III), at a rate of 31 micronmol/h/mg of protein. The rate of hydrolysis increased when phenylalanine in the N-protected dipeptide was replaced with alanine, valine, or leucine or when the octapeptide angiotensin II or the heptapeptide angiotensin III were the substrates. The enzyme also cleaved the angiotensin II antagonist saralasin (Sar1-Ala8-angiotensin II). The Km values were 1 mM, 2mM, and 0.77 mM with Cbz-Pro-Phe, angiotensin II, and angiotensin III, respectively. The enzyme had an acid pH optimum (4.5 to 5.5), but hydrolyzed angiotensin III at pH 7 at 50% of the optimal rate. Prolylcarboxypeptidase was inhibited by diisopropyl phosphorofluoridate and pepstatin, but not by sequestering agents or -SH reagents."}
{"id": "PMID:28325", "title": "Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells.", "content": "In certain lines of hepatoma tissue culture (HTC) cells, glutamine synthetase (EC 6.3.1.2) specific activity is increased 2.5- to 3-fold by the addition of glucocorticoids to the growth media. Actinomycin D blocks both the induction and deinduction of glutamine synthetase by glucocorticoids, suggesting a requirement of RNA synthesis for both processes. Using an antiserum raised against purified rat liver glutamine synthetase, we have precipitated radiolabeled glutamine synthetase from HTC cells. Electrophoresis of the immunoprecipitates on sodium didecyl sulfate-acrylamide gels isolates the subunit of glutamine synthetase and permits the radioactivity in the glutamine synthetase band to be quantitated. Using this technique, we have investigated the effect of dexamethasone, a synthetic glucocorticoid, on the rates of synthesis and degradation of glutamine synthetase. Dexamethasone (10(-7) M) increases the rate of synthesis of glutamine synthetase 2- to 3-fold but has no effect on the rate of glutamine synthetase degradation. The rates of total cell protein synthesis and degradation are not significantly affected by dexamethasone. The presence of actinomycin D at the time of removal of dexamethasone from induced cells prevents the fall in the induced rate of synthesis of glutamine synthetase normally seen when the inhibitor is removed from the culture medium. The regulation of glutamine synthetase by dexamethasone has been compared to the regulation of another dexamethasone-inducible enzyme in HTC cells, tyrosine aminotransferase, and been found to be similar in all parameters studied.", "contents": "Regulation of glutamine synthetase by dexamethasone in hepatoma tissue culture cells. In certain lines of hepatoma tissue culture (HTC) cells, glutamine synthetase (EC 6.3.1.2) specific activity is increased 2.5- to 3-fold by the addition of glucocorticoids to the growth media. Actinomycin D blocks both the induction and deinduction of glutamine synthetase by glucocorticoids, suggesting a requirement of RNA synthesis for both processes. Using an antiserum raised against purified rat liver glutamine synthetase, we have precipitated radiolabeled glutamine synthetase from HTC cells. Electrophoresis of the immunoprecipitates on sodium didecyl sulfate-acrylamide gels isolates the subunit of glutamine synthetase and permits the radioactivity in the glutamine synthetase band to be quantitated. Using this technique, we have investigated the effect of dexamethasone, a synthetic glucocorticoid, on the rates of synthesis and degradation of glutamine synthetase. Dexamethasone (10(-7) M) increases the rate of synthesis of glutamine synthetase 2- to 3-fold but has no effect on the rate of glutamine synthetase degradation. The rates of total cell protein synthesis and degradation are not significantly affected by dexamethasone. The presence of actinomycin D at the time of removal of dexamethasone from induced cells prevents the fall in the induced rate of synthesis of glutamine synthetase normally seen when the inhibitor is removed from the culture medium. The regulation of glutamine synthetase by dexamethasone has been compared to the regulation of another dexamethasone-inducible enzyme in HTC cells, tyrosine aminotransferase, and been found to be similar in all parameters studied."}
{"id": "PMID:28326", "title": "Biosynthesis in Escherichia coli of sn-glycerol 3-phosphate, a precursor of phospholipid. Kinetic characterization of wild type and feedback-resistant forms of the biosynthetic sn-glycerol-3-phosphate dehydrogenase.", "content": "Homogeneous wild type and feedback-resistant forms of the biosynthetic sn-glycerol 3-phosphate (glycerol-P) dehydrogenase of Escherichia coli (EC1.1.1.8) were subjected to two-substrate kinetic analysis. The kinetics of the NADPH-dependent reduction of dihydroxyacetone phosphate (dihydroxyacetone-P) and of the NADP-dependent oxidation of glycerol-P indicate that these reactions proceed by a sequential mechanism. Glycerol-P was a competitive inhibitor with respect to dihydroxyacetone-P for both enzymes. The wild type and feedback-resistant glycerol-P dehydrogenases had Ki values for glycerol-P of 4.4 micrometer and 43 micrometer, respectively. Therefore, the sensitivity of the wild type activity and reduced sensitivity of the feedback-resistant activity, both noted previously in crude extracts, were inherent properties of the enzymes. The patterns of product inhibition for both enzymes were identical, and the difference in the inhibition constants for glycerol-P occurred without significant alteration of any other kinetic constant determined. Kinetic mechanisms consistent with the patterns of product inhibition violated Haldane relationships and other kinetic relationships. These discrepancies suggest that glycerol-P inhibition occurs at a site distinct from the active site. The pH dependencies of the Km for dihydroxyacetone-P and the Ki for glycerol-P were markedly different suggesting the existence of an allosteric site. The addition of glycerol-P in the presence of NADPH stabilized both enzymes against thermal inactivation. Half-maximal stabilization was provided by 5 micrometer and 50 micrometer glycerol-P for the wild type and feedback-resistant enzymes, respectively. These kinetic data, considered in conjunction with previous physiologic and genetic data, indicate that the synthesis of glycerol-P is regulated in vivo by glycerol-P inhibition of the glycerol-P dehydrogenase. The data suggest that glycerol-P inhibition occurs at an allosteric, regulatory site.", "contents": "Biosynthesis in Escherichia coli of sn-glycerol 3-phosphate, a precursor of phospholipid. Kinetic characterization of wild type and feedback-resistant forms of the biosynthetic sn-glycerol-3-phosphate dehydrogenase. Homogeneous wild type and feedback-resistant forms of the biosynthetic sn-glycerol 3-phosphate (glycerol-P) dehydrogenase of Escherichia coli (EC1.1.1.8) were subjected to two-substrate kinetic analysis. The kinetics of the NADPH-dependent reduction of dihydroxyacetone phosphate (dihydroxyacetone-P) and of the NADP-dependent oxidation of glycerol-P indicate that these reactions proceed by a sequential mechanism. Glycerol-P was a competitive inhibitor with respect to dihydroxyacetone-P for both enzymes. The wild type and feedback-resistant glycerol-P dehydrogenases had Ki values for glycerol-P of 4.4 micrometer and 43 micrometer, respectively. Therefore, the sensitivity of the wild type activity and reduced sensitivity of the feedback-resistant activity, both noted previously in crude extracts, were inherent properties of the enzymes. The patterns of product inhibition for both enzymes were identical, and the difference in the inhibition constants for glycerol-P occurred without significant alteration of any other kinetic constant determined. Kinetic mechanisms consistent with the patterns of product inhibition violated Haldane relationships and other kinetic relationships. These discrepancies suggest that glycerol-P inhibition occurs at a site distinct from the active site. The pH dependencies of the Km for dihydroxyacetone-P and the Ki for glycerol-P were markedly different suggesting the existence of an allosteric site. The addition of glycerol-P in the presence of NADPH stabilized both enzymes against thermal inactivation. Half-maximal stabilization was provided by 5 micrometer and 50 micrometer glycerol-P for the wild type and feedback-resistant enzymes, respectively. These kinetic data, considered in conjunction with previous physiologic and genetic data, indicate that the synthesis of glycerol-P is regulated in vivo by glycerol-P inhibition of the glycerol-P dehydrogenase. The data suggest that glycerol-P inhibition occurs at an allosteric, regulatory site."}
{"id": "PMID:28329", "title": "Bovine thymus poly(adenosine diphosphate ribose) polymerase.", "content": "About 1,300-fold purification of poly(adenosine diphosphate ribose) polymerase has been achieved from the extract of bovine thymus with a recovery of 10 to 20%. The final preparation has a purity of 99%, and the enzyme is composed of a single peptide with a molecular weight of 130,000. The purified enzyme required NAD+, Mg2+, a thiol compound, DNA, and histones for full activity. Whereas DNA is essential for activation of the enzyme, histones are not. The observed stimulation of the reaction by histones is shown to be due to masking of the inhibitory effect of contaminating denartured DNA in native DNA preparation. The concentration of DNA required for half-maximal enzyme activity (apparent Km for DNA) is proportional to the concentration of enzyme in the reaction mixture. The minimum estimation of the number of nucleotide pairs of DNA required for half-maximal activation of one enzyme molecule is 220 to 240 for bulk of calf thymus DNA, while the value is 10 for a calf thymus DNA fraction, \"active DNA,\" which was separated from the enzyme fraction in a stage of the purification. These results suggest that the enzyme is activated by binding to a specific site on calf thymus DNA. The apparent Km for NAD+ and the maximum velocity of the enzyme are estimated to be 60 micrometer and 0.91 mumolper min per mg, respectively.", "contents": "Bovine thymus poly(adenosine diphosphate ribose) polymerase. About 1,300-fold purification of poly(adenosine diphosphate ribose) polymerase has been achieved from the extract of bovine thymus with a recovery of 10 to 20%. The final preparation has a purity of 99%, and the enzyme is composed of a single peptide with a molecular weight of 130,000. The purified enzyme required NAD+, Mg2+, a thiol compound, DNA, and histones for full activity. Whereas DNA is essential for activation of the enzyme, histones are not. The observed stimulation of the reaction by histones is shown to be due to masking of the inhibitory effect of contaminating denartured DNA in native DNA preparation. The concentration of DNA required for half-maximal enzyme activity (apparent Km for DNA) is proportional to the concentration of enzyme in the reaction mixture. The minimum estimation of the number of nucleotide pairs of DNA required for half-maximal activation of one enzyme molecule is 220 to 240 for bulk of calf thymus DNA, while the value is 10 for a calf thymus DNA fraction, \"active DNA,\" which was separated from the enzyme fraction in a stage of the purification. These results suggest that the enzyme is activated by binding to a specific site on calf thymus DNA. The apparent Km for NAD+ and the maximum velocity of the enzyme are estimated to be 60 micrometer and 0.91 mumolper min per mg, respectively."}
{"id": "PMID:28332", "title": "Actin filament destruction by osmium tetroxide.", "content": "We have studied the destruction of purified muscle actin filaments by osmium tetroxide (OsO4) to develop methods to preserve actin filaments during preparation for electron microscopy. Actin filaments are fragmented during exposure to OsO4. This causes the viscosity of solutions of actin filaments to decrease, ultimately to zero, and provides a convenient quantitative assay to analyze the reaction. The rate of filament destruction is determined by the OsO4 concentration, temperature, buffer type and concentration, and pH. Filament destruction is minimized by treatment with a low concentration of OsO4 in sodium phosphate buffer, pH 6.0, at 0 degrees C. Under these conditions, the viscosity of actin filament solutions is stable and actin filaments retain their straight, unbranched structure, even after dehydration and embedding. Under more severe conditions, the straight actin filaments are converted into what look like the microfilament networks commonly observed in cells fixed with OsO4. Destruction of actin filaments can be inhibited by binding tropomyosin to the actin. Cross-linking the actin molecules within a filament with glutaraldehyde does not prevent their destruction by OsO4. The viscosity decrease requires the continued presence of free OsO4. During the time of the viscosity change, OsO4 is reduced and the sulfur-containing amino acids of actin are oxidized, but little of the osmium is bound to the actin. Over a much longer time span, the actin molecules are split into discrete peptides.", "contents": "Actin filament destruction by osmium tetroxide. We have studied the destruction of purified muscle actin filaments by osmium tetroxide (OsO4) to develop methods to preserve actin filaments during preparation for electron microscopy. Actin filaments are fragmented during exposure to OsO4. This causes the viscosity of solutions of actin filaments to decrease, ultimately to zero, and provides a convenient quantitative assay to analyze the reaction. The rate of filament destruction is determined by the OsO4 concentration, temperature, buffer type and concentration, and pH. Filament destruction is minimized by treatment with a low concentration of OsO4 in sodium phosphate buffer, pH 6.0, at 0 degrees C. Under these conditions, the viscosity of actin filament solutions is stable and actin filaments retain their straight, unbranched structure, even after dehydration and embedding. Under more severe conditions, the straight actin filaments are converted into what look like the microfilament networks commonly observed in cells fixed with OsO4. Destruction of actin filaments can be inhibited by binding tropomyosin to the actin. Cross-linking the actin molecules within a filament with glutaraldehyde does not prevent their destruction by OsO4. The viscosity decrease requires the continued presence of free OsO4. During the time of the viscosity change, OsO4 is reduced and the sulfur-containing amino acids of actin are oxidized, but little of the osmium is bound to the actin. Over a much longer time span, the actin molecules are split into discrete peptides."}
{"id": "PMID:28335", "title": "Interference in word associations in schizophrenia.", "content": "Assessed the effect of response interference on the word associations of male and female process and reactive schizophrenics in two studies that used the difference in associative disturbances between high and low interference (low and high commonality stimulus words) as the measure. The reactives showed a significantly greater increase in disturbances in the high interference condition than did process schizophrenics in both studies. These results occurred in process and reactive groups that did not differ in age, IQ, institutionalization, and current level of physiological arousal and symptom severity in Study I. Findings supported predictions from a qualitative differences theory of cognitive deficit in schizophrenia.", "contents": "Interference in word associations in schizophrenia. Assessed the effect of response interference on the word associations of male and female process and reactive schizophrenics in two studies that used the difference in associative disturbances between high and low interference (low and high commonality stimulus words) as the measure. The reactives showed a significantly greater increase in disturbances in the high interference condition than did process schizophrenics in both studies. These results occurred in process and reactive groups that did not differ in age, IQ, institutionalization, and current level of physiological arousal and symptom severity in Study I. Findings supported predictions from a qualitative differences theory of cognitive deficit in schizophrenia."}
{"id": "PMID:28336", "title": "Psychophysiological responses to presentation of a caged snake among behaviorally avoidant and non-avoidant college students.", "content": "Sixty-six coeds who reported fear of snakes on a paper-and-pencil fear inventory were exposed to a Physiological Response Test, during which their electrodermal and cardiac responses to a neutral stimulus and a caged snake were recorded. Half of these coeds then were exposed to a representative Behavioral Avoidance Test, on the basis of which they were classified as avoidant, as non-avoidant, or as neither. Those remaining were classified similarly with an Incentive Behavioral Avoidation Test, before which each was offered an incentive for displaying non-fearfulness. The electrodermal response data showed that students classifed as avoidant had not been more responsive to snake confrontation than the the students classified as non-avoidant. The cardiac response data showed that avoidant Ss had been relatively more responsive to the snake cue, but that differential responsiveness was not robust. These results held for both behavioral avoidance tests.", "contents": "Psychophysiological responses to presentation of a caged snake among behaviorally avoidant and non-avoidant college students. Sixty-six coeds who reported fear of snakes on a paper-and-pencil fear inventory were exposed to a Physiological Response Test, during which their electrodermal and cardiac responses to a neutral stimulus and a caged snake were recorded. Half of these coeds then were exposed to a representative Behavioral Avoidance Test, on the basis of which they were classified as avoidant, as non-avoidant, or as neither. Those remaining were classified similarly with an Incentive Behavioral Avoidation Test, before which each was offered an incentive for displaying non-fearfulness. The electrodermal response data showed that students classifed as avoidant had not been more responsive to snake confrontation than the the students classified as non-avoidant. The cardiac response data showed that avoidant Ss had been relatively more responsive to the snake cue, but that differential responsiveness was not robust. These results held for both behavioral avoidance tests."}
{"id": "PMID:28337", "title": "Facilitating and debilitating test anxiety among college students and volunteers for desensitization workshops.", "content": "Administered the Alpert-Haber Achievement Anxiety Test (AAT) to 54 students who expressed interest in participating in a test anxiety desensitization workshop. In addition, 182 students from the general college population were tested. Results indicated that both the debilitating and facilitating (AAT) scales were higher for the self-referred volunteer group. These data indicate that these scales are useful in distinguishing self-referred volunteers for behavior modification workshops from a general college population. In addition, the scales of the AAT were correlated with the number of sessions attended by those students who enrolled in the desensitization groups. Results indicated no relationship between attrition and debilitating anxiety. There was a correlation of r = .318 p less than .15 between facilitating anxiety scores and number of sessions attended. It is suggested that facilitating anxiety can function as a measure of S's ego strength in predicting workshop attendance.", "contents": "Facilitating and debilitating test anxiety among college students and volunteers for desensitization workshops. Administered the Alpert-Haber Achievement Anxiety Test (AAT) to 54 students who expressed interest in participating in a test anxiety desensitization workshop. In addition, 182 students from the general college population were tested. Results indicated that both the debilitating and facilitating (AAT) scales were higher for the self-referred volunteer group. These data indicate that these scales are useful in distinguishing self-referred volunteers for behavior modification workshops from a general college population. In addition, the scales of the AAT were correlated with the number of sessions attended by those students who enrolled in the desensitization groups. Results indicated no relationship between attrition and debilitating anxiety. There was a correlation of r = .318 p less than .15 between facilitating anxiety scores and number of sessions attended. It is suggested that facilitating anxiety can function as a measure of S's ego strength in predicting workshop attendance."}
{"id": "PMID:28339", "title": "Reduction in enamel dissolution by liquorice and glycyrrhizinic acid.", "content": "Liquorice extracts and confections reduced enamel dissolution in acidic buffers and saliva/glucose incubations by a direct effect on solubility, and by inhibiting the fall in pH on incubation. These actions may be attributed to the solubility-reducing, glycolysis-inhibiting, and buffering properties of glycyrrhizinic acid, a constituent of liquorice.", "contents": "Reduction in enamel dissolution by liquorice and glycyrrhizinic acid. Liquorice extracts and confections reduced enamel dissolution in acidic buffers and saliva/glucose incubations by a direct effect on solubility, and by inhibiting the fall in pH on incubation. These actions may be attributed to the solubility-reducing, glycolysis-inhibiting, and buffering properties of glycyrrhizinic acid, a constituent of liquorice."}
{"id": "PMID:28340", "title": "An electrochemical study on the human dental enamel with special reference to isoelectric point.", "content": "In an attempt to make a dynamic study of the isoelectric point and the chargeability of human dental enamel, an electrochemical approach was utilized. Zeta potential of three kinds of the enamel was measured by a streaming potential method. As a result, these isoelectric points could be decided.", "contents": "An electrochemical study on the human dental enamel with special reference to isoelectric point. In an attempt to make a dynamic study of the isoelectric point and the chargeability of human dental enamel, an electrochemical approach was utilized. Zeta potential of three kinds of the enamel was measured by a streaming potential method. As a result, these isoelectric points could be decided."}
{"id": "PMID:28341", "title": "Effect of 4.5--year use of xylitol and sorbitol on plaque.", "content": "The pH values of xylitol-containing plaque suspensions of persons who habitually used xylitol and sorbitol during 3.2 to 4.5 years did not significantly differ from those observed with suspensions containing no added carbohydrates. Sorbitol produced in 22-hour incubations pH values as low as 3.9 to 5.5. The activity of plaque xylitol dehydrogenase was almost nil, whereas sorbitol dehydrogenase activity was higher. The nonacidogenic nature of xylitol in relation to plaque did not change in prolonged use of xylitol.", "contents": "Effect of 4.5--year use of xylitol and sorbitol on plaque. The pH values of xylitol-containing plaque suspensions of persons who habitually used xylitol and sorbitol during 3.2 to 4.5 years did not significantly differ from those observed with suspensions containing no added carbohydrates. Sorbitol produced in 22-hour incubations pH values as low as 3.9 to 5.5. The activity of plaque xylitol dehydrogenase was almost nil, whereas sorbitol dehydrogenase activity was higher. The nonacidogenic nature of xylitol in relation to plaque did not change in prolonged use of xylitol."}
{"id": "PMID:28342", "title": "Effect of progestins on androgen delta4-3-ketosteroid-5alpha-A-ring reductase system in rat oral mucosa.", "content": "Rat oral mucosa microsomal delta4-3-ketosteroid-5alpha-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates.", "contents": "Effect of progestins on androgen delta4-3-ketosteroid-5alpha-A-ring reductase system in rat oral mucosa. Rat oral mucosa microsomal delta4-3-ketosteroid-5alpha-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates."}
{"id": "PMID:28343", "title": "Child abuse and dentistry: orofacial trauma and its recognition by dentists.", "content": "Orofacial trauma was found in 49% of 260 documented cases of child abuse seen during of five-year period at the Children's Hospital Medical Center, Boston. An additional 16% of the cases involved head trauma; the total percentage of head and facial trauma was 65%. Head or facial trauma was the principal reason for admission to the hospital in 45% of the cases. A survey of 537 dentists in Massachusetts showed that the majority were unaware of their legal and social responsibilities to report suspected cases of child abuse. Eleven percent of all dentists surveyed saw orofacial trauma cases that were of a suspicious nature, by only 22 confirmed cases of child abuse were noted by the dentists. Of these, only four were reported to social agencies. In general, oral surgeons and pedodontists saw a higher percentage of these cases and were more aware of their responsibilities than were general practitioners.", "contents": "Child abuse and dentistry: orofacial trauma and its recognition by dentists. Orofacial trauma was found in 49% of 260 documented cases of child abuse seen during of five-year period at the Children's Hospital Medical Center, Boston. An additional 16% of the cases involved head trauma; the total percentage of head and facial trauma was 65%. Head or facial trauma was the principal reason for admission to the hospital in 45% of the cases. A survey of 537 dentists in Massachusetts showed that the majority were unaware of their legal and social responsibilities to report suspected cases of child abuse. Eleven percent of all dentists surveyed saw orofacial trauma cases that were of a suspicious nature, by only 22 confirmed cases of child abuse were noted by the dentists. Of these, only four were reported to social agencies. In general, oral surgeons and pedodontists saw a higher percentage of these cases and were more aware of their responsibilities than were general practitioners."}
{"id": "PMID:28346", "title": "[A new instrument for measurement of actual instantaneous pH in obstetric (author's transl)].", "content": "The authors present a new instrument for measurement of actual instantaneous pH in obstetrics. It has been developped to avoid most errors of the usual scalp-blood sampling. Its advantages are:--Aspiration is manual and controlled.--Results are obtained within 10--15 seconds. A comparative study with two other pH-meters has demonstrated an excellent correlation and reliability of this new instrument. The authors consider the method as simple, functional and reliable, all favourable factors for routine use.", "contents": "[A new instrument for measurement of actual instantaneous pH in obstetric (author's transl)]. The authors present a new instrument for measurement of actual instantaneous pH in obstetrics. It has been developped to avoid most errors of the usual scalp-blood sampling. Its advantages are:--Aspiration is manual and controlled.--Results are obtained within 10--15 seconds. A comparative study with two other pH-meters has demonstrated an excellent correlation and reliability of this new instrument. The authors consider the method as simple, functional and reliable, all favourable factors for routine use."}
{"id": "PMID:28350", "title": "Polyarteritis: A cause of nerve palsy in the extremity.", "content": "The association between polyarteritis and peripheral neuropathy may be overlooked in the clinical assessment of nerve lesions in the extremity. Nerve palsy may be the initial presenting complaint in polyarteritis nodosa. A case is presented which demonstrates the pathological process. A method for early recognition and treatment is suggested.", "contents": "Polyarteritis: A cause of nerve palsy in the extremity. The association between polyarteritis and peripheral neuropathy may be overlooked in the clinical assessment of nerve lesions in the extremity. Nerve palsy may be the initial presenting complaint in polyarteritis nodosa. A case is presented which demonstrates the pathological process. A method for early recognition and treatment is suggested."}
{"id": "PMID:28369", "title": "Low molecular weight C1q-precipitins in hypocomplementemic vasculitis-urticaria syndrome: partial purification and characterization as immunoglobulin.", "content": "A lupus-like syndrome involving chronic urticaria with cutaneous vasculitis, systemic symptoms, hypocomplementemia with preferential depletion of C1q, and low m.w. (7S) C1q-precipitins has recently been defined. The C1q-precipitin activity (C1q-p) seems to represent a diagnostic marker of the disease, but its chemical nature is not yet clear. We have partially purified and characterized C1q-p from the serum of two patients with this syndrome and compared its activity with the C1q-precipitating activity of aggregated human gamma-globulin (AHGG) anti-C1q antibodies, and several polynucleotides including DNA and polyinosinic acid. C1q-p was found to partition with IgG during precipitation by ammonium sulfate and low ionic strength buffer as well as during column chromatography on DEAE-cellulose and G-200 Sephadex. Like AHGG, but in complete contrast to the polynucleotides, the C1q-precipitating activity of C1q-p was sensitive to pepsin, trypsin, and acidic conditions, but unaffected by DNAse or RNAse; the C1q-precipitating activity of anti-C1q antibody was not diminished by any of these procedures. Thus, C1q-p consists of gamma-migrating protein of low m.w., and its C1q-precipitating activity is indistinguishable from that of AHGG. These results are consistent with the concept that C1q-p is comprised, at least in part, of IgG that binds C1q via the Fc portion of the molecule.", "contents": "Low molecular weight C1q-precipitins in hypocomplementemic vasculitis-urticaria syndrome: partial purification and characterization as immunoglobulin. A lupus-like syndrome involving chronic urticaria with cutaneous vasculitis, systemic symptoms, hypocomplementemia with preferential depletion of C1q, and low m.w. (7S) C1q-precipitins has recently been defined. The C1q-precipitin activity (C1q-p) seems to represent a diagnostic marker of the disease, but its chemical nature is not yet clear. We have partially purified and characterized C1q-p from the serum of two patients with this syndrome and compared its activity with the C1q-precipitating activity of aggregated human gamma-globulin (AHGG) anti-C1q antibodies, and several polynucleotides including DNA and polyinosinic acid. C1q-p was found to partition with IgG during precipitation by ammonium sulfate and low ionic strength buffer as well as during column chromatography on DEAE-cellulose and G-200 Sephadex. Like AHGG, but in complete contrast to the polynucleotides, the C1q-precipitating activity of C1q-p was sensitive to pepsin, trypsin, and acidic conditions, but unaffected by DNAse or RNAse; the C1q-precipitating activity of anti-C1q antibody was not diminished by any of these procedures. Thus, C1q-p consists of gamma-migrating protein of low m.w., and its C1q-precipitating activity is indistinguishable from that of AHGG. These results are consistent with the concept that C1q-p is comprised, at least in part, of IgG that binds C1q via the Fc portion of the molecule."}
{"id": "PMID:28370", "title": "Characterization of human hairbulb tyrosinase: properties of normal and albino enzyme.", "content": "Human hairbulb tyrosinase from normally pigmented and tyrosinase-positive oculocutaneous albino (TPA) hairbulbs was studied by single hairbulb and by pooled hairbulb assay procedures. The response to temperature and pH was the same for TPA and normal enzyme. The Km for tyrosine as substrate and the Km or dopa as cofactor was the same for TPA and normal enzyme. These studies show that TPA tyrosinase is kinetically normal and that the defect with this form of albinism must be elsewhere in the melanin pathway.", "contents": "Characterization of human hairbulb tyrosinase: properties of normal and albino enzyme. Human hairbulb tyrosinase from normally pigmented and tyrosinase-positive oculocutaneous albino (TPA) hairbulbs was studied by single hairbulb and by pooled hairbulb assay procedures. The response to temperature and pH was the same for TPA and normal enzyme. The Km for tyrosine as substrate and the Km or dopa as cofactor was the same for TPA and normal enzyme. These studies show that TPA tyrosinase is kinetically normal and that the defect with this form of albinism must be elsewhere in the melanin pathway."}
{"id": "PMID:28372", "title": "Endogenous angiotensin I concentration in human plasma.", "content": "A reliable radioimmunoassay of endogenous angiotensin I concentration in plasma, extracted on a Dowex-resin at pH 7.4, is described. The concentration of angiotensin I in the pH 7.4-extracted plasma samples is significantly correlated with the angiotensin I concentration in the samples extracted at pH 5.5, the pH optimum of the in vitro reaction of human renin with human renin substrate. The presence of immunoreactive angiotensin I-like material in plasma and the relatively high cross-reaction of renin substrate with the anti-angiotensin I antiserum necessitates a chromatographic purification on a Dowex resin. The normal range found for angiotensin I in venous blood of apparently normal, male subjects was 25 to 143 pg/ml. A significant correlation (r = 0.78; p less than 0.001) between PA-I and PRA was found in normal subjects. No differences (p greater than 0.10) between arterial and venous angiotensin I concentration were observed in hypertensive patients.", "contents": "Endogenous angiotensin I concentration in human plasma. A reliable radioimmunoassay of endogenous angiotensin I concentration in plasma, extracted on a Dowex-resin at pH 7.4, is described. The concentration of angiotensin I in the pH 7.4-extracted plasma samples is significantly correlated with the angiotensin I concentration in the samples extracted at pH 5.5, the pH optimum of the in vitro reaction of human renin with human renin substrate. The presence of immunoreactive angiotensin I-like material in plasma and the relatively high cross-reaction of renin substrate with the anti-angiotensin I antiserum necessitates a chromatographic purification on a Dowex resin. The normal range found for angiotensin I in venous blood of apparently normal, male subjects was 25 to 143 pg/ml. A significant correlation (r = 0.78; p less than 0.001) between PA-I and PRA was found in normal subjects. No differences (p greater than 0.10) between arterial and venous angiotensin I concentration were observed in hypertensive patients."}
{"id": "PMID:28373", "title": "Supersaturation of urine with uric acid and urate: response to a uricosuric diuretic.", "content": "In order to assess the possibility that treatment with the uricosuric diuretic ticrynafen (tienilic acid) could lead to UA or MSU crystalluria, the degree of urinary supersaturation with respect to these crystalloids was assessed in persons receiving the diuretic for 1 week, and the results were compared with similar data generated from the use of probenecid. Initially, only probenecid significantly increased the degree of urinary suspersaturation with respect to MSU, and after adjustment of urine pH values to 5.5, probenecid also increased the degree of urinary supersaturation with respect to nonionized UA. At a pH of 5.5, the urine was significantly more supersaturated with nonionized UA after a single dose of probenecid than after ticrynafen (tienilic acid). Ticrynafen never significantly affected the degree of urinary supersaturation with respect to UA or MSU. Neither agent affected small amounts of \"colloidal\" or \"bound\" urinary urate. Insofar as the degree of urinary supersaturation with these crystalloids predisposes to crystalluria and calculus formation, ticrynafen (tienilic acid) appears to present no increased risk.", "contents": "Supersaturation of urine with uric acid and urate: response to a uricosuric diuretic. In order to assess the possibility that treatment with the uricosuric diuretic ticrynafen (tienilic acid) could lead to UA or MSU crystalluria, the degree of urinary supersaturation with respect to these crystalloids was assessed in persons receiving the diuretic for 1 week, and the results were compared with similar data generated from the use of probenecid. Initially, only probenecid significantly increased the degree of urinary suspersaturation with respect to MSU, and after adjustment of urine pH values to 5.5, probenecid also increased the degree of urinary supersaturation with respect to nonionized UA. At a pH of 5.5, the urine was significantly more supersaturated with nonionized UA after a single dose of probenecid than after ticrynafen (tienilic acid). Ticrynafen never significantly affected the degree of urinary supersaturation with respect to UA or MSU. Neither agent affected small amounts of \"colloidal\" or \"bound\" urinary urate. Insofar as the degree of urinary supersaturation with these crystalloids predisposes to crystalluria and calculus formation, ticrynafen (tienilic acid) appears to present no increased risk."}
{"id": "PMID:28376", "title": "Renal regulation of acid-base balance in a freshwater fish (1).", "content": "Intra-arterial injection of a fixed acid load caused only a short-lived (less than 2h) disturbance of blood pH but a long lived (2-3 days) elevation of urinary acid excretion in freshwater trout (Salmo gairdneri). The renal response comprised an immediate increase in acid output in the form of titratable acidity minus bicarbonate, and a slower rise in acid output in the form of ammonia. The total elevation in urinary acid efflux over 72h was such that no other mechanism besides renal function is needed to explain the ultimate compensation of this experimental acid-base disturbance.", "contents": "Renal regulation of acid-base balance in a freshwater fish (1). Intra-arterial injection of a fixed acid load caused only a short-lived (less than 2h) disturbance of blood pH but a long lived (2-3 days) elevation of urinary acid excretion in freshwater trout (Salmo gairdneri). The renal response comprised an immediate increase in acid output in the form of titratable acidity minus bicarbonate, and a slower rise in acid output in the form of ammonia. The total elevation in urinary acid efflux over 72h was such that no other mechanism besides renal function is needed to explain the ultimate compensation of this experimental acid-base disturbance."}
{"id": "PMID:28377", "title": "The isolation of a Bwamba virus variant from man in Western Kenya.", "content": "A bwamba group virus was isolated from the blood of a febrile child on the Kano Plain, Kenya. The isolate (NY-45), closely resembling Bwamba, established infection in both Anopheles gambiae and Mansonia uniformis. Neither the Bwamba nor the Pongola prototype strains grew in both species. In gel-diffusion tests NY-45 virus passaged through mosquitoes exhibited a line of identity with Pongola antiserum. In contrast no cross-reaction was observed with NY-45 virus which had not previously been passaged through mosquitoes.", "contents": "The isolation of a Bwamba virus variant from man in Western Kenya. A bwamba group virus was isolated from the blood of a febrile child on the Kano Plain, Kenya. The isolate (NY-45), closely resembling Bwamba, established infection in both Anopheles gambiae and Mansonia uniformis. Neither the Bwamba nor the Pongola prototype strains grew in both species. In gel-diffusion tests NY-45 virus passaged through mosquitoes exhibited a line of identity with Pongola antiserum. In contrast no cross-reaction was observed with NY-45 virus which had not previously been passaged through mosquitoes."}
{"id": "PMID:28378", "title": "Effect of a new benzodiazepine bromazepam on locomotor performance and brain monoamine metabolism.", "content": "Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in P2 pellet. Bromazepam failed to change 3H-norepinephrine and 3H-5-hydroxytryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to laterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindole-acetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turn over. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain.", "contents": "Effect of a new benzodiazepine bromazepam on locomotor performance and brain monoamine metabolism. Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in P2 pellet. Bromazepam failed to change 3H-norepinephrine and 3H-5-hydroxytryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to laterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindole-acetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turn over. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain."}
{"id": "PMID:28379", "title": "Biosynthesis and processing of presumed neurosecretory proteins in single identified neurons of Aplysia californica.", "content": "The biosynthesis and processing of low molecular weight protein (presumed neurosecretory protein) in cells R15, R14 and L11 of Aplysia californica was studied at high resolution by polyacrylamide slab gel electrophoresis in sodium dodecylsulfate. The number of low molecular weight proteins detected in each cell ranges from 3 in R14 and L11 to 5 to 6 in R15. In each of the cells studied, the low molecular weight protein consists of a primary precursor of ca. 12,000 daltons, and its proteolytic processing products. In each cell, the smallest protein, or in the case of R14, one of the two smallest proteins, accumulates to a significant extent, suggesting that it might correspond to a final processed neurohormone. In cell R15, the biosynthesis of the primary precursor and its subsequent processing to smaller peptides is largely unaffected by removal of extracellular calcium, by replacement of calcium with cobalt or by inhibition of spontaneous bursting via stimulation of the brachial nerve.", "contents": "Biosynthesis and processing of presumed neurosecretory proteins in single identified neurons of Aplysia californica. The biosynthesis and processing of low molecular weight protein (presumed neurosecretory protein) in cells R15, R14 and L11 of Aplysia californica was studied at high resolution by polyacrylamide slab gel electrophoresis in sodium dodecylsulfate. The number of low molecular weight proteins detected in each cell ranges from 3 in R14 and L11 to 5 to 6 in R15. In each of the cells studied, the low molecular weight protein consists of a primary precursor of ca. 12,000 daltons, and its proteolytic processing products. In each cell, the smallest protein, or in the case of R14, one of the two smallest proteins, accumulates to a significant extent, suggesting that it might correspond to a final processed neurohormone. In cell R15, the biosynthesis of the primary precursor and its subsequent processing to smaller peptides is largely unaffected by removal of extracellular calcium, by replacement of calcium with cobalt or by inhibition of spontaneous bursting via stimulation of the brachial nerve."}
{"id": "PMID:28387", "title": "Evidence for a change in neurotransmitter affecting oesophageal motility in Parkinson's disease.", "content": "In a study of oesophageal motility in 20 patients with Parkinson's disease, intravenous atropine produced marked disruption of co-ordination in response to swallows, when compared with control subjects. This suggests that cholinergic rather than dopaminergic mechanisms are more important in the control of swallowing in patients with Parkinsonism. No conclusive evidence of peripheral dopamine depletion or autonomic neuropathy was found, although minor changes suggestive of the former were found in severely affected patients.", "contents": "Evidence for a change in neurotransmitter affecting oesophageal motility in Parkinson's disease. In a study of oesophageal motility in 20 patients with Parkinson's disease, intravenous atropine produced marked disruption of co-ordination in response to swallows, when compared with control subjects. This suggests that cholinergic rather than dopaminergic mechanisms are more important in the control of swallowing in patients with Parkinsonism. No conclusive evidence of peripheral dopamine depletion or autonomic neuropathy was found, although minor changes suggestive of the former were found in severely affected patients."}
{"id": "PMID:28388", "title": "Radioiodinated derivatives of beta adrenoceptor blockers for myocardial imaging.", "content": "Four new beta-adrenoceptor blocking agents carrying tyramine as the amino moiety were synthesized and the distribution of their I-125-tagged derivatives evaluated in rats. This distribution was compared with the distribution of various agonists and antagonists labeled with H-3 and C-14, and with the in vitro binding affinity of the new derivatives. A radioiodinated derivative of a cardioselective blocker, alprenolol, showed poor blood clearance and no cardiac selectivity. A derivative of another cardioselective blocker, practolol, showed a promising heart-to-blood ratio (ca. 19) and cardioselectivity with a heart-to-lung ratio of ca. 2. Two additional practolol analogs showed no improvement over the practolol derivative; because of the increased lipophilicity of these derivatives, blood clearance and cardioselectivity were diminished. An inverse correlation is suggested between the dissociation constant for the beta adrenoceptor in the lung and the heart-to-blood and heart-to-lung values. We conclude that polarity plays an important role in the blood clearance and cardioselectivity of these beta-adrenoceptor derivatives.", "contents": "Radioiodinated derivatives of beta adrenoceptor blockers for myocardial imaging. Four new beta-adrenoceptor blocking agents carrying tyramine as the amino moiety were synthesized and the distribution of their I-125-tagged derivatives evaluated in rats. This distribution was compared with the distribution of various agonists and antagonists labeled with H-3 and C-14, and with the in vitro binding affinity of the new derivatives. A radioiodinated derivative of a cardioselective blocker, alprenolol, showed poor blood clearance and no cardiac selectivity. A derivative of another cardioselective blocker, practolol, showed a promising heart-to-blood ratio (ca. 19) and cardioselectivity with a heart-to-lung ratio of ca. 2. Two additional practolol analogs showed no improvement over the practolol derivative; because of the increased lipophilicity of these derivatives, blood clearance and cardioselectivity were diminished. An inverse correlation is suggested between the dissociation constant for the beta adrenoceptor in the lung and the heart-to-blood and heart-to-lung values. We conclude that polarity plays an important role in the blood clearance and cardioselectivity of these beta-adrenoceptor derivatives."}
{"id": "PMID:28389", "title": "Experimental cross infections of Fasciola hepatica in lambs and calves.", "content": "The effects of experimental infections with Fasciola hepatica of ovine and bovine origin in homologous and heterologous hosts and in uninfected controls were compared; groups comprised 5 animals each. The effects of the infections were monitored by biweekly determinations of packed cell volumes (PCV), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transpeptidase (GGT), serum iron, bilirubin levels, alkaline phosphatase (AlP) and total serum protein levels. Infected animals showed changes in SGOT, SGPT and GGT activity levels, and GGT activity levels, and infected lambs showed changes in PCV and AlP. However, no no significant differences in these serum levels between infected host groups were attributable to fluke strain. At necropsy, calves infected with ovine and bovine strains on an average had about the same number of flukes, but lambs infected with a high dose of the bovine strain on the average had nearly twice the number of flukes as those infected with ovine strain. Weight gains did not differ within host groups; liver damage was extensive in all infected animals. On the basis of these experiments, the pathogenicity of the ovine and the bovine strains of F. hepatica appears to be the same.", "contents": "Experimental cross infections of Fasciola hepatica in lambs and calves. The effects of experimental infections with Fasciola hepatica of ovine and bovine origin in homologous and heterologous hosts and in uninfected controls were compared; groups comprised 5 animals each. The effects of the infections were monitored by biweekly determinations of packed cell volumes (PCV), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transpeptidase (GGT), serum iron, bilirubin levels, alkaline phosphatase (AlP) and total serum protein levels. Infected animals showed changes in SGOT, SGPT and GGT activity levels, and GGT activity levels, and infected lambs showed changes in PCV and AlP. However, no no significant differences in these serum levels between infected host groups were attributable to fluke strain. At necropsy, calves infected with ovine and bovine strains on an average had about the same number of flukes, but lambs infected with a high dose of the bovine strain on the average had nearly twice the number of flukes as those infected with ovine strain. Weight gains did not differ within host groups; liver damage was extensive in all infected animals. On the basis of these experiments, the pathogenicity of the ovine and the bovine strains of F. hepatica appears to be the same."}
{"id": "PMID:28390", "title": "Isolation and partial characterization of trehalase from Ascaris muscle.", "content": "The tissues of female Ascaris suum were assayed for alpha,apha'-glucoside 1-D-glucohydrolase (trehalase) activity. A soluble from of the enzyme was isolated from muscle tissue and purified approximately 37-fold. The enzyme was specific for trehalose as substrate. The pH optimum for enzymatic activity was found to be 6.0, and the apparent Km for trehalose was estimated to be 2.1 x 10-4 M. The product of the reaction was identified as D-glucose by chemical, chromatographic and enzymatic methods.", "contents": "Isolation and partial characterization of trehalase from Ascaris muscle. The tissues of female Ascaris suum were assayed for alpha,apha'-glucoside 1-D-glucohydrolase (trehalase) activity. A soluble from of the enzyme was isolated from muscle tissue and purified approximately 37-fold. The enzyme was specific for trehalose as substrate. The pH optimum for enzymatic activity was found to be 6.0, and the apparent Km for trehalose was estimated to be 2.1 x 10-4 M. The product of the reaction was identified as D-glucose by chemical, chromatographic and enzymatic methods."}
{"id": "PMID:28391", "title": "The interaction of preservatives with polyhydroxyethylmethacrylate (polyHEMA).", "content": "The interaction of the four most commonly used preservatives in contact lens solutions (chlorbutol, thiomersal, chlorhexidine gluconate and benzalkonium chloride) with polyhydroxyethylmethacrylate (polyHEMA), has been examined. Benzalkonium chloride and chlorhexidine gluconate show typical high affinity type isotherms. The interaction of benzalkonium chloride with polyHEMA from aqueous solution was reversible whereas that of chlorhexidine was only reversible in the presence of electrolyte or surfactant. Chlorbutol showed a typical reversible linear isotherm. Thiomersal does not interact with polyHEMA above pH 5.0. The extent of chlorhexidine--polyHEMA interactions in increased by the presence of formulatory adjuvants such as electrolyte and hydrophilic polymers. PolyHEMA lenses that apparently have been equilibrated with chlorhexidine gluconate will, on the addition of fresh preservative solution, bind further quantities of chlorhexidine above that which would be predicted from the sorption isotherm.", "contents": "The interaction of preservatives with polyhydroxyethylmethacrylate (polyHEMA). The interaction of the four most commonly used preservatives in contact lens solutions (chlorbutol, thiomersal, chlorhexidine gluconate and benzalkonium chloride) with polyhydroxyethylmethacrylate (polyHEMA), has been examined. Benzalkonium chloride and chlorhexidine gluconate show typical high affinity type isotherms. The interaction of benzalkonium chloride with polyHEMA from aqueous solution was reversible whereas that of chlorhexidine was only reversible in the presence of electrolyte or surfactant. Chlorbutol showed a typical reversible linear isotherm. Thiomersal does not interact with polyHEMA above pH 5.0. The extent of chlorhexidine--polyHEMA interactions in increased by the presence of formulatory adjuvants such as electrolyte and hydrophilic polymers. PolyHEMA lenses that apparently have been equilibrated with chlorhexidine gluconate will, on the addition of fresh preservative solution, bind further quantities of chlorhexidine above that which would be predicted from the sorption isotherm."}
{"id": "PMID:28392", "title": "Theory of the mean absorption time, an adjunct to conventional bioavailability studies.", "content": "The theory is outlined of a procedure for characterizing the time-course of drug absorption by determining the mean absorption time. The procedure requires data of the type normally collected in bioavailability studies.", "contents": "Theory of the mean absorption time, an adjunct to conventional bioavailability studies. The theory is outlined of a procedure for characterizing the time-course of drug absorption by determining the mean absorption time. The procedure requires data of the type normally collected in bioavailability studies."}
{"id": "PMID:28393", "title": "Bioavailability of griseofulvin from a novel capsule formulation.", "content": "The in vivo availability of griseofulvin from a novel formulation has been compared with the micronized powder. The formulation technique involves the conversion of the hydrophobic surface of the drug to a hydrophilic one by treatment with a film forming polymer. This enhances the wettability of the power, and increases its dissolution rate. The results of the in vivo study show the formulation technique has increased the rate and extent of bioavailability of griseofulvin when compared with the non-treated powder.", "contents": "Bioavailability of griseofulvin from a novel capsule formulation. The in vivo availability of griseofulvin from a novel formulation has been compared with the micronized powder. The formulation technique involves the conversion of the hydrophobic surface of the drug to a hydrophilic one by treatment with a film forming polymer. This enhances the wettability of the power, and increases its dissolution rate. The results of the in vivo study show the formulation technique has increased the rate and extent of bioavailability of griseofulvin when compared with the non-treated powder."}
{"id": "PMID:28394", "title": "The relation between molecular connectivity and gas chromatographic retention data.", "content": "The recently developed topological index, molecular connectivity (chi), has been correlated using multiple regression analysis with gas chromatographic retention time (Rt) for various series of compounds. For saturated and unsaturated aliphatic hydrocarbons, and aliphatic aldehydes, good correlation with log Rt was achieved by one-parameter linear equations in terms of the first-order conncectivity index. (1chi). The equation for aliphatic alcohols required an additional parameter, the valence connectivity (vchi) for satisfactory correlation. One-parameter equations using 1chi also good correlation with log Rt for three series of drug molecules, amphetamines, barbiturates and phenothiazines. In all cases the equations generated gave good agreement between calculated and observed log Rt values.", "contents": "The relation between molecular connectivity and gas chromatographic retention data. The recently developed topological index, molecular connectivity (chi), has been correlated using multiple regression analysis with gas chromatographic retention time (Rt) for various series of compounds. For saturated and unsaturated aliphatic hydrocarbons, and aliphatic aldehydes, good correlation with log Rt was achieved by one-parameter linear equations in terms of the first-order conncectivity index. (1chi). The equation for aliphatic alcohols required an additional parameter, the valence connectivity (vchi) for satisfactory correlation. One-parameter equations using 1chi also good correlation with log Rt for three series of drug molecules, amphetamines, barbiturates and phenothiazines. In all cases the equations generated gave good agreement between calculated and observed log Rt values."}
{"id": "PMID:28395", "title": "The percutaneous absorption of phenolic compounds: the mechanism of diffusion across the stratum corneum.", "content": "The effect of temperature on the permeation of phenolic compounds from aqueous solution through excised human skin has been examined. From a thermodynamic analysis of the data, a mechanism is postulated by which these solutes penetrate through human skin. For the more polar solutes it is suggested that the main resistance to penetration is the lipid barriers in the stratum corneum. Diffusion of these substances through the stratum corneum appears to depend on the breaking of hydrogen bonds in the desolvation of the solute during this penetration process and by the overall 'viscosity' of the stratum corneum. With non-polar solutes, the aqueous boundary layers appear to provide an additional barrier to the penetration of phenolic compounds.", "contents": "The percutaneous absorption of phenolic compounds: the mechanism of diffusion across the stratum corneum. The effect of temperature on the permeation of phenolic compounds from aqueous solution through excised human skin has been examined. From a thermodynamic analysis of the data, a mechanism is postulated by which these solutes penetrate through human skin. For the more polar solutes it is suggested that the main resistance to penetration is the lipid barriers in the stratum corneum. Diffusion of these substances through the stratum corneum appears to depend on the breaking of hydrogen bonds in the desolvation of the solute during this penetration process and by the overall 'viscosity' of the stratum corneum. With non-polar solutes, the aqueous boundary layers appear to provide an additional barrier to the penetration of phenolic compounds."}
{"id": "PMID:28396", "title": "The character of the antagonism by polyphloretin phosphate of contractions to prostaglandins E1 and F 2alpha in guinea-pig ileum.", "content": "Polyphloretin phosphate (PPP) produced a dose-dependent decrease in the tone and reduction of the spontaneous phasic contactions of the longitudinal muscle of guinea-pig isolated ileum. PPP (100 microgram ml-1) after a 2 min contact with the ileum decreased the contractile effects of PGE1 0.1 micron by 40.6 +/- 7.4%, of PGE1 0.01 micron by 86.7 +/- 3.3% and of PGE2alpha 0.1 micron by 62.2 +/- 8.6%. After 10 min contact of PPP the contractile effect of PGE1 0.1 micron was decreased by 47.7 +/- 4.7% and that of PGE2alpha 0.1 micron by 89.6 +/- 1.7%. When the contact was longer, PPP showed a pronounced after-effect in respect to the effects of PGE1 and particularly of PGF2alpha. PPP signicantly reduced contractions to 5-HT and BaCL2, but not to acetylcholine, histamine or substance P. The type of antagonism of PGE1 by PPP was examined using cumulative concentration-effect curves for PGE1 in the presence of increasing concentrations of PPP. We conclude that on guinea-pig ileum PPP acts as a non-competitive antagonist of PGE1 and PGF2alpha.", "contents": "The character of the antagonism by polyphloretin phosphate of contractions to prostaglandins E1 and F 2alpha in guinea-pig ileum. Polyphloretin phosphate (PPP) produced a dose-dependent decrease in the tone and reduction of the spontaneous phasic contactions of the longitudinal muscle of guinea-pig isolated ileum. PPP (100 microgram ml-1) after a 2 min contact with the ileum decreased the contractile effects of PGE1 0.1 micron by 40.6 +/- 7.4%, of PGE1 0.01 micron by 86.7 +/- 3.3% and of PGE2alpha 0.1 micron by 62.2 +/- 8.6%. After 10 min contact of PPP the contractile effect of PGE1 0.1 micron was decreased by 47.7 +/- 4.7% and that of PGE2alpha 0.1 micron by 89.6 +/- 1.7%. When the contact was longer, PPP showed a pronounced after-effect in respect to the effects of PGE1 and particularly of PGF2alpha. PPP signicantly reduced contractions to 5-HT and BaCL2, but not to acetylcholine, histamine or substance P. The type of antagonism of PGE1 by PPP was examined using cumulative concentration-effect curves for PGE1 in the presence of increasing concentrations of PPP. We conclude that on guinea-pig ileum PPP acts as a non-competitive antagonist of PGE1 and PGF2alpha."}
{"id": "PMID:28397", "title": "Direct effect of a nomifensine derivative on dopamine receptors.", "content": "A study was made of the effects of nomifensine, 4'-hydroxynomifensine and 3',4'-dihydroxynomifensine on dopamine receptors in rat striatum and nucleus accumbens, using the dopamine-sensitive adenylate cyclase assay. Nomifensine and its 4'-hydroxy metabolite were both inactive as dopaminergic agonists. 3',4'-dihydroxynomifensine was, however, a potent agonist, being approximately 2 to 4 times less active than dopamine. The effects of dopamine and of 3',4'-dihydroxynomifensine were blocked by fluphenazine. It is concluded that the dopaminergic activity of 3',4'-dihydroxynomifensine is dependent upon the presence of the two hydroxyl groups.", "contents": "Direct effect of a nomifensine derivative on dopamine receptors. A study was made of the effects of nomifensine, 4'-hydroxynomifensine and 3',4'-dihydroxynomifensine on dopamine receptors in rat striatum and nucleus accumbens, using the dopamine-sensitive adenylate cyclase assay. Nomifensine and its 4'-hydroxy metabolite were both inactive as dopaminergic agonists. 3',4'-dihydroxynomifensine was, however, a potent agonist, being approximately 2 to 4 times less active than dopamine. The effects of dopamine and of 3',4'-dihydroxynomifensine were blocked by fluphenazine. It is concluded that the dopaminergic activity of 3',4'-dihydroxynomifensine is dependent upon the presence of the two hydroxyl groups."}
{"id": "PMID:28399", "title": "The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow.", "content": "Systemic and regional haemodynamic variables were measured at the baseline and after saline or 5-HT infusions (5 microgram kg-1 min-1, i.v.) or methysergide injections (0.5 mg kg-1, i.v.). Cardiac output and its complete distribution were measured by the radioactive microsphere (15 micrometer diam) technique. Although 5-HT did not change the systemic variables, methysergide caused a moderate increase in systolic and mean blood pressure and heart rate. 5-HT caused a substantial increase in gastric and a moderate increase in cerebral and myocardial blood flow at the expense of that to the lungs (arteriovenous shunt + bronchial flows), kidneys and skin. While methysergide was able to reduce the vascular responses to 5-HT in stomach, skin, kidneys, heart, lungs and brain, the drug itself, like 5-HT, decreased the number of microspheres reaching the lungs. Since a large number of 15 micron microspheres can escape through the arteriovenous anastomoses to lodge in the lungs it seems likely that both 5-HT and methysergide can reduce the 'non-nutrient' flow through these anastomoses.", "contents": "The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow. Systemic and regional haemodynamic variables were measured at the baseline and after saline or 5-HT infusions (5 microgram kg-1 min-1, i.v.) or methysergide injections (0.5 mg kg-1, i.v.). Cardiac output and its complete distribution were measured by the radioactive microsphere (15 micrometer diam) technique. Although 5-HT did not change the systemic variables, methysergide caused a moderate increase in systolic and mean blood pressure and heart rate. 5-HT caused a substantial increase in gastric and a moderate increase in cerebral and myocardial blood flow at the expense of that to the lungs (arteriovenous shunt + bronchial flows), kidneys and skin. While methysergide was able to reduce the vascular responses to 5-HT in stomach, skin, kidneys, heart, lungs and brain, the drug itself, like 5-HT, decreased the number of microspheres reaching the lungs. Since a large number of 15 micron microspheres can escape through the arteriovenous anastomoses to lodge in the lungs it seems likely that both 5-HT and methysergide can reduce the 'non-nutrient' flow through these anastomoses."}
{"id": "PMID:28414", "title": "Pharmacology of 6,7-dihydroxy-2-dimethylaminotetralin (TL-99). I. Cardiovascular activity in the dog and cat.", "content": "6,7-Dihydroxy-2-dimethylaminotetralin (TL-99), the 5,6-dihydroxy isomer (M-7) and dopamine were studied for cardiovascular activity in the cat and dog. TL-99 was found to be the most active of these compounds. Some of the more striking actions of TL-99 and M-7 were bradycardia, hypotension and complete blockade of norepinephrine-induced reflex activation. A detailed study of these compounds showed that they were most likely exerting their effects by inhibiting sympathetic nervous system activity. Whether these compounds were activating dopamine receptors or alpha adrenergic receptors is not entirely clear from this study.", "contents": "Pharmacology of 6,7-dihydroxy-2-dimethylaminotetralin (TL-99). I. Cardiovascular activity in the dog and cat. 6,7-Dihydroxy-2-dimethylaminotetralin (TL-99), the 5,6-dihydroxy isomer (M-7) and dopamine were studied for cardiovascular activity in the cat and dog. TL-99 was found to be the most active of these compounds. Some of the more striking actions of TL-99 and M-7 were bradycardia, hypotension and complete blockade of norepinephrine-induced reflex activation. A detailed study of these compounds showed that they were most likely exerting their effects by inhibiting sympathetic nervous system activity. Whether these compounds were activating dopamine receptors or alpha adrenergic receptors is not entirely clear from this study."}
{"id": "PMID:28415", "title": "Withdrawal of clonidine: effects of varying dosage or duration of treatment on subsequent blood pressure and heart rate responses.", "content": "The influence of the dosage or duration of treatment on the incidence and severity of clonidine withdrawal responses was examined in normotensive rats. Clonidine (0.01 or 0.1 mg/kg i.m.) was administered either in single doses, or twice daily for 3 days or 3 weeks. Rats were then anesthetized and arterial catheters were inserted. Significant overshoots in blood pressure and heart rate, reaching peak values 16 to 26 hr after the last injection, occurred in all clonidine-treated rats, but in no control rats. The overshoots after single injections of clonidine were as great as those after suspension of sustained treatment. Moreover, withdrawal responses were as great after the low dose as they were after the 10-fold greater dose. Only plasma renin activity showed a significantly greater elevation during withdrawal of the high dose of clonidine. Since ganglionic blockade reduced blood pressures and heart rates to the same levels in rats with clonidine withdrawal hypertension as in control rats, the withdrawal overshoots appear to be nervously mediated. Neither the dosage nor the duration of treatment could be shown to determine the magnitude of the response to withdrawal of clonidine.", "contents": "Withdrawal of clonidine: effects of varying dosage or duration of treatment on subsequent blood pressure and heart rate responses. The influence of the dosage or duration of treatment on the incidence and severity of clonidine withdrawal responses was examined in normotensive rats. Clonidine (0.01 or 0.1 mg/kg i.m.) was administered either in single doses, or twice daily for 3 days or 3 weeks. Rats were then anesthetized and arterial catheters were inserted. Significant overshoots in blood pressure and heart rate, reaching peak values 16 to 26 hr after the last injection, occurred in all clonidine-treated rats, but in no control rats. The overshoots after single injections of clonidine were as great as those after suspension of sustained treatment. Moreover, withdrawal responses were as great after the low dose as they were after the 10-fold greater dose. Only plasma renin activity showed a significantly greater elevation during withdrawal of the high dose of clonidine. Since ganglionic blockade reduced blood pressures and heart rates to the same levels in rats with clonidine withdrawal hypertension as in control rats, the withdrawal overshoots appear to be nervously mediated. Neither the dosage nor the duration of treatment could be shown to determine the magnitude of the response to withdrawal of clonidine."}
{"id": "PMID:28417", "title": "The black physician's assistant: problems and prospects.", "content": "This is a report on a study of the social origins, attitudes, and anticipated practice settings of black and white recruits to the physician's assistant occupation. Recruits are generally representative of the larger black and white communities in their values; however, black recruits are more likely than their white counterparts to value the status, income, and stability perceived to be associated with the occupation. At the same time, blacks are more likely to favor national health insurance and to look forward to servicing the poor. These liberal social attitudes and the finding that blacks are more likely than whites to desire to practice in ghetto areas provide some support for affirmative action policies in dealing with the health manpower needs of medically underserviced areas.", "contents": "The black physician's assistant: problems and prospects. This is a report on a study of the social origins, attitudes, and anticipated practice settings of black and white recruits to the physician's assistant occupation. Recruits are generally representative of the larger black and white communities in their values; however, black recruits are more likely than their white counterparts to value the status, income, and stability perceived to be associated with the occupation. At the same time, blacks are more likely to favor national health insurance and to look forward to servicing the poor. These liberal social attitudes and the finding that blacks are more likely than whites to desire to practice in ghetto areas provide some support for affirmative action policies in dealing with the health manpower needs of medically underserviced areas."}
{"id": "PMID:28421", "title": "Suppression of mitogen responses and graft-versus-host reaction by splenocytes from mice bearing Lewis lung carcinoma.", "content": "The presence of suppressor cells in the spleens of C57BL/6 mice bearing Lewis lung carcinoma was investigated with the use of the in vitro lymphoproliferative response to mitogens and the graft-versus-host reaction (GVHR) as test systems. Splenocytes from tumor-bearing mice showed a lower response to mitogens when obtained 15-27 days after tumor transplant. In parallel, these cells were capable of suppressing the response of normal spleen cells to mitogens and their capacity to mount a GVHR in allogeneic hosts. Treatments with procedures known to remove adherent phagocytes, but not treatments with anti-Thy 1.2 serum plus complement, removed the suppressive activity observed.", "contents": "Suppression of mitogen responses and graft-versus-host reaction by splenocytes from mice bearing Lewis lung carcinoma. The presence of suppressor cells in the spleens of C57BL/6 mice bearing Lewis lung carcinoma was investigated with the use of the in vitro lymphoproliferative response to mitogens and the graft-versus-host reaction (GVHR) as test systems. Splenocytes from tumor-bearing mice showed a lower response to mitogens when obtained 15-27 days after tumor transplant. In parallel, these cells were capable of suppressing the response of normal spleen cells to mitogens and their capacity to mount a GVHR in allogeneic hosts. Treatments with procedures known to remove adherent phagocytes, but not treatments with anti-Thy 1.2 serum plus complement, removed the suppressive activity observed."}
{"id": "PMID:28422", "title": "Transfer of viable putative preneoplastic hepatocytes to the livers of syngeneic host rats.", "content": "A new approach was developed by which freshly isolated, chemical carcinogen-altered hepatocytes with the positive marker gamma-glutamyl transpeptidase (gamma-GT) could be transferred from adult donor F344 rats to the livers of syngeneic, adult host rats. Selective proliferation of gamma-GT-positive hepatocytes was induced in host rat livers, such that large, macroscopic colonies of altered hepatocytes could be generated within 10 days of the cell transfer operation. Quantitation of the number of gamma-GT-positive hepatocyte colonies (foci) appearing per square centimeter of host liver section area on day 10 following cell transfer revealed that prior treatment of host rats with a low dose of 2-acetylaminofluorene was essential for the appearance of large numbers of foci. In addition, the appearance of foci on day 10 depended on the presence of intact, gamma-GT-positive hepatocytes in the infused (transferred) cell suspensions.", "contents": "Transfer of viable putative preneoplastic hepatocytes to the livers of syngeneic host rats. A new approach was developed by which freshly isolated, chemical carcinogen-altered hepatocytes with the positive marker gamma-glutamyl transpeptidase (gamma-GT) could be transferred from adult donor F344 rats to the livers of syngeneic, adult host rats. Selective proliferation of gamma-GT-positive hepatocytes was induced in host rat livers, such that large, macroscopic colonies of altered hepatocytes could be generated within 10 days of the cell transfer operation. Quantitation of the number of gamma-GT-positive hepatocyte colonies (foci) appearing per square centimeter of host liver section area on day 10 following cell transfer revealed that prior treatment of host rats with a low dose of 2-acetylaminofluorene was essential for the appearance of large numbers of foci. In addition, the appearance of foci on day 10 depended on the presence of intact, gamma-GT-positive hepatocytes in the infused (transferred) cell suspensions."}
{"id": "PMID:28424", "title": "Prostatic maldevelopment in the prune belly syndrome: a defect in prostatic stromal-epithelial interaction.", "content": "The prune belly syndrome consists of a triad of abdominal wall musculature deficiency, cryptorchidism and urinary tract anomalies. A rarely described but fairly constant component of the syndrome is the lack of development of the epithelial elements of the prostate. We wish to suggest that this is a further expression of a postulated arrest in mesenchymal development responsible for other features of the syndrome.", "contents": "Prostatic maldevelopment in the prune belly syndrome: a defect in prostatic stromal-epithelial interaction. The prune belly syndrome consists of a triad of abdominal wall musculature deficiency, cryptorchidism and urinary tract anomalies. A rarely described but fairly constant component of the syndrome is the lack of development of the epithelial elements of the prostate. We wish to suggest that this is a further expression of a postulated arrest in mesenchymal development responsible for other features of the syndrome."}
{"id": "PMID:28425", "title": "Bone marrow transplantation for acute myeloblastic leukemia.", "content": "Fifty-seven patients with end-stage acute myeloblastic leukemia (AML) received a total of 65 bone marrow transplants between 1968 and 1976. Marrow from HLA genotypically identical allogeneic donors was administered to 32 patients, 13 received marrow from HLA-incompatible donors, donor-recipient HLA compatibility was undetermined for eight patients, and identical twins were marrow donors for four patients. None of the patients  in the three latter groups survived beyond 9.4 months after transplantation. Two patients treated with marrow transplants from HLA-compatible donors currently are alive and free of leukemia with functioning grafts 13 and 38 months after transplantation. The 32 patients in the Registry series who received marrow from HLA-compatible donors were compared with a similar series of 46 patients in Seattle. Data for these 78 patients were pooled and analyzed for pretransplant factors that might have prognostic value. Patients with end-stage AML had approximately a 10% chance of surviving 20 months after high-dose chemoradiotherapy plus marrow transplantation. Patients younger than 21 years had a higher six-month survival rate than patients older than 30 years. Patients in the Registry series who received transplants with HLA-compatible marrow within eight months of diagnosis had a higher survival experience than patients who received transplants later.", "contents": "Bone marrow transplantation for acute myeloblastic leukemia. Fifty-seven patients with end-stage acute myeloblastic leukemia (AML) received a total of 65 bone marrow transplants between 1968 and 1976. Marrow from HLA genotypically identical allogeneic donors was administered to 32 patients, 13 received marrow from HLA-incompatible donors, donor-recipient HLA compatibility was undetermined for eight patients, and identical twins were marrow donors for four patients. None of the patients  in the three latter groups survived beyond 9.4 months after transplantation. Two patients treated with marrow transplants from HLA-compatible donors currently are alive and free of leukemia with functioning grafts 13 and 38 months after transplantation. The 32 patients in the Registry series who received marrow from HLA-compatible donors were compared with a similar series of 46 patients in Seattle. Data for these 78 patients were pooled and analyzed for pretransplant factors that might have prognostic value. Patients with end-stage AML had approximately a 10% chance of surviving 20 months after high-dose chemoradiotherapy plus marrow transplantation. Patients younger than 21 years had a higher six-month survival rate than patients older than 30 years. Patients in the Registry series who received transplants with HLA-compatible marrow within eight months of diagnosis had a higher survival experience than patients who received transplants later."}
{"id": "PMID:28449", "title": "Single-mouse urine collection and pH monitoring system.", "content": "A glass cage with minimal surface area was designed and used to house mice for 24-hour urine collections. An experiment was performed with a radio-labeled compound excreted in the urine to assess the collection efficiency of the cage. In this experiment 74.2 +/- 6.5% of the excreted radioactivity was recovered in the urine, with 25.8 +/- 6.5% found adhering to the cage surfaces. When a flow-through pH electrode, meter, and recorder were attached, the system provided a continuous pH versus time urination record.", "contents": "Single-mouse urine collection and pH monitoring system. A glass cage with minimal surface area was designed and used to house mice for 24-hour urine collections. An experiment was performed with a radio-labeled compound excreted in the urine to assess the collection efficiency of the cage. In this experiment 74.2 +/- 6.5% of the excreted radioactivity was recovered in the urine, with 25.8 +/- 6.5% found adhering to the cage surfaces. When a flow-through pH electrode, meter, and recorder were attached, the system provided a continuous pH versus time urination record."}
{"id": "PMID:28454", "title": "Effects of two adrenergic beta-receptor blockers on the sleep cycle of the cat.", "content": "Sixteen hour polygraphic recordings (EEG, EOG and EMG) were obtained from 14 adult cats after intraperitoneal injections of propranolol (5 mg/kg) or pindolol (0.1 or 0.5 mg/kg). All injections moderately increased waking, which consisted mainly of a sedated drowsy stage. Both drugs also decreased deep slow wave sleep, while light slow wave sleep remained at control levels. The changes were more marked after propranolol, which also significantly reduced paradoxical sleep (PS). The decrease in the deeper stages of sleep and PS is suggested as being due to blockade of the central adrenergic beta-receptors per se and/or antagonistic effects of the beta-blockers on 5-HT receptors. The results agree with the finding that beta-blockers cause insomnia in susceptible patients, but they do not suggest that intensified dreaming or nightmares reported by others are likely to be caused by increased PS.", "contents": "Effects of two adrenergic beta-receptor blockers on the sleep cycle of the cat. Sixteen hour polygraphic recordings (EEG, EOG and EMG) were obtained from 14 adult cats after intraperitoneal injections of propranolol (5 mg/kg) or pindolol (0.1 or 0.5 mg/kg). All injections moderately increased waking, which consisted mainly of a sedated drowsy stage. Both drugs also decreased deep slow wave sleep, while light slow wave sleep remained at control levels. The changes were more marked after propranolol, which also significantly reduced paradoxical sleep (PS). The decrease in the deeper stages of sleep and PS is suggested as being due to blockade of the central adrenergic beta-receptors per se and/or antagonistic effects of the beta-blockers on 5-HT receptors. The results agree with the finding that beta-blockers cause insomnia in susceptible patients, but they do not suggest that intensified dreaming or nightmares reported by others are likely to be caused by increased PS."}
{"id": "PMID:28456", "title": "[Sialographic findings in inflammations of the salivary glands (author's transl)].", "content": "The greatest part of all diseases of salivary glands are caused by inflammations. The differential diagnosis to other diseases, e.g. tumors, if of great importance. The sialography has hereby developed to an important diagnostic measurement. There is a discussion about the technique of the sialography and its simple performance as well as the high effectiveness of this X-ray examination. The X-ray morphology of different kinds of inflammations is various. The acute inflammations are characterized by narrowing of ducts, the subacute inflammations by the pathological staining of the parenchyma, and the chronic by the increased changes of the Stenon's or Wharton's duct, respectively of ducts with superior range.", "contents": "[Sialographic findings in inflammations of the salivary glands (author's transl)]. The greatest part of all diseases of salivary glands are caused by inflammations. The differential diagnosis to other diseases, e.g. tumors, if of great importance. The sialography has hereby developed to an important diagnostic measurement. There is a discussion about the technique of the sialography and its simple performance as well as the high effectiveness of this X-ray examination. The X-ray morphology of different kinds of inflammations is various. The acute inflammations are characterized by narrowing of ducts, the subacute inflammations by the pathological staining of the parenchyma, and the chronic by the increased changes of the Stenon's or Wharton's duct, respectively of ducts with superior range."}
{"id": "PMID:28457", "title": "[Disorders of motility of the stomach and pylorus: pathological significance (author's transl)].", "content": "Five different disorders of motility of the pyloric region may be distinguished if direction and velocity of chyme passing through the pylorus are taken into account: 1. Accelerated emptying of food and overacidification of the bulbus duodeni: 2. Bolus emptying of the stomach and rapid increasing hyperosmolarity in the small intestine: 3. Delayed emptying of the stomach and gastric retention: 4. Duodeno-gastric reflux and inflammatory lesions of the gastric mucosa: 5. Other disorders causing pain. Gastric disroders cannot yet be classified on the basis of abnormal motility patterns. It is well known, that the gastric and duodenal motility are regulated by two separate pacemakers located in the distal corpus area and in the bulbus duodeni. Thus it may be speculated that distrubed motility patterns may be due to abnormal pacemaker function.", "contents": "[Disorders of motility of the stomach and pylorus: pathological significance (author's transl)]. Five different disorders of motility of the pyloric region may be distinguished if direction and velocity of chyme passing through the pylorus are taken into account: 1. Accelerated emptying of food and overacidification of the bulbus duodeni: 2. Bolus emptying of the stomach and rapid increasing hyperosmolarity in the small intestine: 3. Delayed emptying of the stomach and gastric retention: 4. Duodeno-gastric reflux and inflammatory lesions of the gastric mucosa: 5. Other disorders causing pain. Gastric disroders cannot yet be classified on the basis of abnormal motility patterns. It is well known, that the gastric and duodenal motility are regulated by two separate pacemakers located in the distal corpus area and in the bulbus duodeni. Thus it may be speculated that distrubed motility patterns may be due to abnormal pacemaker function."}
{"id": "PMID:28480", "title": "[Methods and problems of investigation of psychopharmacological effect illustrated by the comparison of a novel pyridylbenzodiazepine with diazepam (author's transl)].", "content": "Comparison of two compounds being investigated should take into consideration the most comprehensive spectrum of all psychic variables affected. Consequently, besides 15 standardized investigational methods, three open methods, history, observation of behavior and in particular free exploration were used. The investigation was carried out in 18 ambulant patients who were given the preparations under investigation in a double-blind cross-over trial. Particular problems of the method were the interference of psychotherapeutic effect of the intensive exploration discussions on the action of the preparations, which could be controlled by comparison with a placebo phase, and the effects of learning and stereotype on repeated presentation.", "contents": "[Methods and problems of investigation of psychopharmacological effect illustrated by the comparison of a novel pyridylbenzodiazepine with diazepam (author's transl)]. Comparison of two compounds being investigated should take into consideration the most comprehensive spectrum of all psychic variables affected. Consequently, besides 15 standardized investigational methods, three open methods, history, observation of behavior and in particular free exploration were used. The investigation was carried out in 18 ambulant patients who were given the preparations under investigation in a double-blind cross-over trial. Particular problems of the method were the interference of psychotherapeutic effect of the intensive exploration discussions on the action of the preparations, which could be controlled by comparison with a placebo phase, and the effects of learning and stereotype on repeated presentation."}
{"id": "PMID:28475", "title": "[Effect of anions on inhibition of lactate dehydrogenase by pyruvate].", "content": "The effect of anions Cl- and I- on structural and kinetic properties of LDH was investigated. It was shown that anions are specific inhibitors of LDH competing with pyruvate in the active ternary complex, LDHNADHpyq. The following dissociation constants for the anions were obtained from inhibition data: 0.4 +/- 0.02 and 0.07 +/- 0.01 M for Cl- and I-, respectively. The slope of Hill plot are near 1.0. The anions abolished the inhibition of LDH at high pyruvate concentrations. The following dissociation constants were obtained from these data: 0.1 and 0.015 M for Cl- and I- respectively. The inhibition by anions and the abolishing of substrate inhibition by anions were studied also for the lactate oxidation reaction. The dissociation constants for anions obtained from these data are in good correlation with the constants obtained for the pyruvate reduction reaction. It was concluded that anions do not interact with the group at the catalytic site with pK approximately 7.8, presumably His-195. The degree of pyruvate inhibition does not depend on the buffer system. The differences in the degree of inhibition obtained previously in phosphate, imidazole and tris-buffer systems can be explained by the presence of Cl- anions in the last two buffer. The rate constants of hydroxy leads to keto pyruvate transition was obtained in various buffer systems. It was shown that the hydroxy-form of pyruvate does not cause the inhibition of LDH.", "contents": "[Effect of anions on inhibition of lactate dehydrogenase by pyruvate]. The effect of anions Cl- and I- on structural and kinetic properties of LDH was investigated. It was shown that anions are specific inhibitors of LDH competing with pyruvate in the active ternary complex, LDHNADHpyq. The following dissociation constants for the anions were obtained from inhibition data: 0.4 +/- 0.02 and 0.07 +/- 0.01 M for Cl- and I-, respectively. The slope of Hill plot are near 1.0. The anions abolished the inhibition of LDH at high pyruvate concentrations. The following dissociation constants were obtained from these data: 0.1 and 0.015 M for Cl- and I- respectively. The inhibition by anions and the abolishing of substrate inhibition by anions were studied also for the lactate oxidation reaction. The dissociation constants for anions obtained from these data are in good correlation with the constants obtained for the pyruvate reduction reaction. It was concluded that anions do not interact with the group at the catalytic site with pK approximately 7.8, presumably His-195. The degree of pyruvate inhibition does not depend on the buffer system. The differences in the degree of inhibition obtained previously in phosphate, imidazole and tris-buffer systems can be explained by the presence of Cl- anions in the last two buffer. The rate constants of hydroxy leads to keto pyruvate transition was obtained in various buffer systems. It was shown that the hydroxy-form of pyruvate does not cause the inhibition of LDH."}
{"id": "PMID:28476", "title": "[Acid-base properties and secondary structure of DNA in isoionic solutions].", "content": "Potentiometric titration of DNA in the isoionic solutions has been investigated at different concentrations of the polymer. The intrinsic constants pKo of titrable groups corresponding to the two inflections in the titration curves were calculated by taking into account the electrostatic potential of the macroion. The number of ionogenic groups was evaluated from curves of titration. It has been found that the constants of ionization of both ionogenic groups increased with DNA concentration. The number of ionogenic groups corresponding to the first inflection in titration curves is significantly decreased when the concentration of DNA increases. On the other hand, the number of groups corresponding to the second inflection is slightly increased. Spectrophotometric investigations of isoionic solutions of DNA showed that the molar extinction coefficient increases with the concentration of the polymer. The results are discussed in view of the change of the secondary structure of DNA caused by an increase of its concentration in isoionic solutions.", "contents": "[Acid-base properties and secondary structure of DNA in isoionic solutions]. Potentiometric titration of DNA in the isoionic solutions has been investigated at different concentrations of the polymer. The intrinsic constants pKo of titrable groups corresponding to the two inflections in the titration curves were calculated by taking into account the electrostatic potential of the macroion. The number of ionogenic groups was evaluated from curves of titration. It has been found that the constants of ionization of both ionogenic groups increased with DNA concentration. The number of ionogenic groups corresponding to the first inflection in titration curves is significantly decreased when the concentration of DNA increases. On the other hand, the number of groups corresponding to the second inflection is slightly increased. Spectrophotometric investigations of isoionic solutions of DNA showed that the molar extinction coefficient increases with the concentration of the polymer. The results are discussed in view of the change of the secondary structure of DNA caused by an increase of its concentration in isoionic solutions."}
{"id": "PMID:28477", "title": "[Isolation of matrix RNA coding a tyrosine aminotransferase isoenzyme induced by hydrocortisone from rat liver polyribosomes].", "content": "Messenger RNA (mRNA) capable of coding hydrocortisone induced isoenzyme of tyrosineaminotransferase (TAT) was isolated and purified approximately 5000 times. Highly specific rabbit antibodies to the isoenzyme were obtained. Using these antibodies a specific antibody immunoadsorbent with a high capacity for specific binding to TAT was prepared. From total rat liver polyribosomes induced by hydrocortisone a specific fraction synthesising TAT was isolated by fractionation on the antibody immunoadsorbent. Affinity chromatography using poly(U)--Sephadex 4B allowed to isolate a poly(A)-containing RNA from this polyribosome fraction. The mRNA (15-16S) acts as a matrix in a cell-free protein synthesising system. The extent of purification of the mRNA was estimated by the synthesis of specific protein TAT in the cell-free system.", "contents": "[Isolation of matrix RNA coding a tyrosine aminotransferase isoenzyme induced by hydrocortisone from rat liver polyribosomes]. Messenger RNA (mRNA) capable of coding hydrocortisone induced isoenzyme of tyrosineaminotransferase (TAT) was isolated and purified approximately 5000 times. Highly specific rabbit antibodies to the isoenzyme were obtained. Using these antibodies a specific antibody immunoadsorbent with a high capacity for specific binding to TAT was prepared. From total rat liver polyribosomes induced by hydrocortisone a specific fraction synthesising TAT was isolated by fractionation on the antibody immunoadsorbent. Affinity chromatography using poly(U)--Sephadex 4B allowed to isolate a poly(A)-containing RNA from this polyribosome fraction. The mRNA (15-16S) acts as a matrix in a cell-free protein synthesising system. The extent of purification of the mRNA was estimated by the synthesis of specific protein TAT in the cell-free system."}
{"id": "PMID:28478", "title": "[Acid-base equilibrium of yellow lupine ferrileghemoglobin. potentiometric studies].", "content": "Dissociation of ionizing groups in leghemoglobin from Lupinus Luteus in the wide pH range was studied by potentiometric titration. 16 + 8 groups were shown to the titrated at acid pH. One part of them are normally titrating groups and the other one is associated with some details of protein structure. At neutral pH 4 groups are titrated, the titration of 3 of the show histeresis. Five lysins are normally titrated at the alkaline pH. among them one is possibly responsible for an alkaline dissociation. 13 charged groups take part in the dissociation, 3-4 are titrated inreversibly. The experimental results are analyzed in terms of Linderstrom-Lang-Tanford representation and are discussed on the basis of primary and three-dimentional leghemoglobin structure.", "contents": "[Acid-base equilibrium of yellow lupine ferrileghemoglobin. potentiometric studies]. Dissociation of ionizing groups in leghemoglobin from Lupinus Luteus in the wide pH range was studied by potentiometric titration. 16 + 8 groups were shown to the titrated at acid pH. One part of them are normally titrating groups and the other one is associated with some details of protein structure. At neutral pH 4 groups are titrated, the titration of 3 of the show histeresis. Five lysins are normally titrated at the alkaline pH. among them one is possibly responsible for an alkaline dissociation. 13 charged groups take part in the dissociation, 3-4 are titrated inreversibly. The experimental results are analyzed in terms of Linderstrom-Lang-Tanford representation and are discussed on the basis of primary and three-dimentional leghemoglobin structure."}
{"id": "PMID:28479", "title": "[Nature of the easily melted portions of DNA with a quasi-random base sequence].", "content": "The influence of denaturation conditions upon the character of partial denaturation of DNA with random base distribution were thoroughly studied. Maps of partial DNA denaturation were obtained at T less than TAT for phage phiB DNA at pH 10.7 and 5.5; Tg9 DNA at pH 8.8; at T less than TAT for phiB DNA at pH 10.9 and Tg9 DNA at pH 8.8. The map quality was better when obtained at higher pH values; the peaks became sharper and higher against the background. We failed to obtain maps of partial denaturation at pH 5.5, T less than TAT. The improvement of the map quality and existence of the partial denaturation maps at T less than TAT at pH 10.9 were explained by the increase of primary melting probability of AT-rich DNA regions. At high pH the denaturation map quality was temperature independent. This was explained by a very weak temperature dependence of primary melting probability for all maps of equal quality. The map quality became worse, when the quantity of loops was increased.", "contents": "[Nature of the easily melted portions of DNA with a quasi-random base sequence]. The influence of denaturation conditions upon the character of partial denaturation of DNA with random base distribution were thoroughly studied. Maps of partial DNA denaturation were obtained at T less than TAT for phage phiB DNA at pH 10.7 and 5.5; Tg9 DNA at pH 8.8; at T less than TAT for phiB DNA at pH 10.9 and Tg9 DNA at pH 8.8. The map quality was better when obtained at higher pH values; the peaks became sharper and higher against the background. We failed to obtain maps of partial denaturation at pH 5.5, T less than TAT. The improvement of the map quality and existence of the partial denaturation maps at T less than TAT at pH 10.9 were explained by the increase of primary melting probability of AT-rich DNA regions. At high pH the denaturation map quality was temperature independent. This was explained by a very weak temperature dependence of primary melting probability for all maps of equal quality. The map quality became worse, when the quantity of loops was increased."}
{"id": "PMID:28483", "title": "Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease.", "content": "To determine if a normal antibody response can develop after therapy for Hodgkin's disease, we immunized 53 patients and 10 normal controls with dodecavalent pneumococcal vaccine. Antibody concentrations three weeks after immunization (geometric mean of 11 serotypes) were 1566 ng of protein nitrogen per milliliter in controls, 963 ng per milliliter after subtotal radiation (P less than 0.05 compared to controls), 658 ng per milliliter after chemotherapy (P less than 0.05), 377 ng per milliliter after subtotal radiation plus chemotherapy (P less than 0.01) and 283 ng per milliliter after total nodal radiation plus chemotherapy (P less 0.001). Low levels of antibody before immunization correlated with a poor response (r = +0.73, P less than 0.001). The ability to respond to immunization improved significantly but did not return to normal as long as four years after combined therapy. The antibody response to pneumococcal vaccine is profoundly impaired in patients who have received intensive treatment for Hodgkin's disease: the ability of this vaccine to protect them from overwhelming postsplenectomy infections remains in doubt.", "contents": "Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease. To determine if a normal antibody response can develop after therapy for Hodgkin's disease, we immunized 53 patients and 10 normal controls with dodecavalent pneumococcal vaccine. Antibody concentrations three weeks after immunization (geometric mean of 11 serotypes) were 1566 ng of protein nitrogen per milliliter in controls, 963 ng per milliliter after subtotal radiation (P less than 0.05 compared to controls), 658 ng per milliliter after chemotherapy (P less than 0.05), 377 ng per milliliter after subtotal radiation plus chemotherapy (P less than 0.01) and 283 ng per milliliter after total nodal radiation plus chemotherapy (P less 0.001). Low levels of antibody before immunization correlated with a poor response (r = +0.73, P less than 0.001). The ability to respond to immunization improved significantly but did not return to normal as long as four years after combined therapy. The antibody response to pneumococcal vaccine is profoundly impaired in patients who have received intensive treatment for Hodgkin's disease: the ability of this vaccine to protect them from overwhelming postsplenectomy infections remains in doubt."}
{"id": "PMID:28486", "title": "The positive inotropic effect of phenylephrine in the presence of propranolol. Increase in time to peak force and in relaxation time without increase in c-AMP.", "content": "The effects of phenylephrine on the shape of the contraction curve and on the cyclic adenosine 3',5'-monophosphate (c-AMP) content were studied in electrically driven (frequency 0.2 Hz) cat papillary muscles. All experiments were done in the presence of 1 micron propranolol in order to minimize interference from beta-adrenoceptors. 1. Phenylephrine increased the force of contraction in a concentration-dependent manner. Maximal effects (about 200% of control) occurred at 30 micron phenylephrine. 2. The positive inotropic effect (PIE) of phenylephrine was antagonized by phentolamine. Phentolamine, 5 micron, produced a parallel shift of the concentration-response curve for the PIE of phenylephrine by about two log units to the right. 3. The PIE of 30 micron phenylephrine occurred without any detectable increase in the c-AMP levels of the preparations. 4. The PIE of 30 micron phenylephrine developed about three times more slowly than the PIE of an equieffective concentration of isoprenaline. 5. The PIE of phenylephrine was accompanied by significant, concentration-dependent increases in both time to peak force and relaxation time. 6. It is concluded that the PIE of phenylephrine in the presence of propranolol is mediated mainly by a stimulation of alpha-adrenoceptors. It is unlikely to be related to an increase in c-AMP. With respect to time course and influence on the shape of the contraction curve it is qualitatively different from the effects of beta-adrenoceptor stimulation. These data are taken to support the hypothesis that the mechanical effects of alpha- and beta-adrenoceptor stimulating agents on the heart are produced by different mechanisms.", "contents": "The positive inotropic effect of phenylephrine in the presence of propranolol. Increase in time to peak force and in relaxation time without increase in c-AMP. The effects of phenylephrine on the shape of the contraction curve and on the cyclic adenosine 3',5'-monophosphate (c-AMP) content were studied in electrically driven (frequency 0.2 Hz) cat papillary muscles. All experiments were done in the presence of 1 micron propranolol in order to minimize interference from beta-adrenoceptors. 1. Phenylephrine increased the force of contraction in a concentration-dependent manner. Maximal effects (about 200% of control) occurred at 30 micron phenylephrine. 2. The positive inotropic effect (PIE) of phenylephrine was antagonized by phentolamine. Phentolamine, 5 micron, produced a parallel shift of the concentration-response curve for the PIE of phenylephrine by about two log units to the right. 3. The PIE of 30 micron phenylephrine occurred without any detectable increase in the c-AMP levels of the preparations. 4. The PIE of 30 micron phenylephrine developed about three times more slowly than the PIE of an equieffective concentration of isoprenaline. 5. The PIE of phenylephrine was accompanied by significant, concentration-dependent increases in both time to peak force and relaxation time. 6. It is concluded that the PIE of phenylephrine in the presence of propranolol is mediated mainly by a stimulation of alpha-adrenoceptors. It is unlikely to be related to an increase in c-AMP. With respect to time course and influence on the shape of the contraction curve it is qualitatively different from the effects of beta-adrenoceptor stimulation. These data are taken to support the hypothesis that the mechanical effects of alpha- and beta-adrenoceptor stimulating agents on the heart are produced by different mechanisms."}
{"id": "PMID:28488", "title": "Isolation and properties of gamma-glutamyltranspeptidase from Morris hepatoma 5123D.", "content": "gamma-Glutamyltranspeptidase was purified 600-fold from Morris hepatoma 5123D by six-step procedure. Its apparent molecular weight estimated by centrifugation in sucrose gradient with Triton X-100 amounts to 108 000. Some dipeptides particularly glycylglycine and several amino acids considerably increase the enzyme activity but L-serine with borate decreases it. Usually transfer activity of the enzyme towards gamma-L-glutamyl substrates was much higher than hydrolytic. The best substrate for the hepatoma enzyme is reduced glutathione.", "contents": "Isolation and properties of gamma-glutamyltranspeptidase from Morris hepatoma 5123D. gamma-Glutamyltranspeptidase was purified 600-fold from Morris hepatoma 5123D by six-step procedure. Its apparent molecular weight estimated by centrifugation in sucrose gradient with Triton X-100 amounts to 108 000. Some dipeptides particularly glycylglycine and several amino acids considerably increase the enzyme activity but L-serine with borate decreases it. Usually transfer activity of the enzyme towards gamma-L-glutamyl substrates was much higher than hydrolytic. The best substrate for the hepatoma enzyme is reduced glutathione."}
{"id": "PMID:28490", "title": "Comparative study of miscellaneous properties of cysteine sulfinate transaminase and glutamate oxaloacetate transaminase in chick retina homogenate.", "content": "The activity, properties, and developmental pattern of cysteine sulfinate transaminase (CSA-T) were studied in chick retina and compared with the activity, properties, and developmental pattern of glutamate oxaloacetate transaminase (GOT). Their optimum pH is identical whereas the effect of pyridoxal phosphate seems to be different. Developmental patterns are also different. The Km and Vm of CSA-T and GOT were determined in chick retina homogenate. These results suggest that two different enzymes are responsible for the transamination of cysteine sulfinate (CSA) and aspartate.", "contents": "Comparative study of miscellaneous properties of cysteine sulfinate transaminase and glutamate oxaloacetate transaminase in chick retina homogenate. The activity, properties, and developmental pattern of cysteine sulfinate transaminase (CSA-T) were studied in chick retina and compared with the activity, properties, and developmental pattern of glutamate oxaloacetate transaminase (GOT). Their optimum pH is identical whereas the effect of pyridoxal phosphate seems to be different. Developmental patterns are also different. The Km and Vm of CSA-T and GOT were determined in chick retina homogenate. These results suggest that two different enzymes are responsible for the transamination of cysteine sulfinate (CSA) and aspartate."}
{"id": "PMID:28491", "title": "Acid proteinase of hypothalamus. Purification, some properties, and action on somatostatin and substance P.", "content": "In a continuing study of the physiological role of protein breakdown in the hypothalamus, acid proteinase from bovine hypothalamus was purified about 1000-fold. The molecular weight of the enzyme was approximately 50,000. Masimal activity against hemoglobin was obtained at pH 3.2-3.5; serum albumin was split much more slowly. Hypothalamus acid proteinase was partially inhibited by beta-phenyl pyruvate, or benzethonium Cl, and was completely inhibited by low concentrations of pepstatin. This proteinase splits somatostatin, substance P, and analogs of substance P. The probable sites of enzyme action on these peptides were determined by the end group dansyl technique. The enzyme, most likely cathepsin D, may play an important role in the formation and breakdown of peptide hormones in the hypothalamus.", "contents": "Acid proteinase of hypothalamus. Purification, some properties, and action on somatostatin and substance P. In a continuing study of the physiological role of protein breakdown in the hypothalamus, acid proteinase from bovine hypothalamus was purified about 1000-fold. The molecular weight of the enzyme was approximately 50,000. Masimal activity against hemoglobin was obtained at pH 3.2-3.5; serum albumin was split much more slowly. Hypothalamus acid proteinase was partially inhibited by beta-phenyl pyruvate, or benzethonium Cl, and was completely inhibited by low concentrations of pepstatin. This proteinase splits somatostatin, substance P, and analogs of substance P. The probable sites of enzyme action on these peptides were determined by the end group dansyl technique. The enzyme, most likely cathepsin D, may play an important role in the formation and breakdown of peptide hormones in the hypothalamus."}
{"id": "PMID:28500", "title": "The pharmacologic inhibition of premature labor.", "content": "Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to be better than placebo in the inhibition of premature labor, and the beta adrenergic agents appear to be more effective than alcohol. Prostaglandin inhibitors such as indomethacin are currently under investigation. Success is correlated with early administration of the therapy, which requires treating some patients whose contractions might have stopped spontaneoulsy. As different factors may be involved in triggering premature labor, if one therapeutic approach fails another should be initiated promptly.", "contents": "The pharmacologic inhibition of premature labor. Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to be better than placebo in the inhibition of premature labor, and the beta adrenergic agents appear to be more effective than alcohol. Prostaglandin inhibitors such as indomethacin are currently under investigation. Success is correlated with early administration of the therapy, which requires treating some patients whose contractions might have stopped spontaneoulsy. As different factors may be involved in triggering premature labor, if one therapeutic approach fails another should be initiated promptly."}
{"id": "PMID:28501", "title": "Studies on vaginal malodor. I. Study in humans.", "content": "Forty-two percent of collagen sponges tested as an intravaginal barrier contraceptive method developed malodor when retained for 5 days. Only 4% developed odor when the sponge was removed within 24 hours after intercourse, rinsed, and reinserted. While sexually active volunteers found odor in 37% of the sponges, odor formed only in 4% of the sponges worn by sexually inactive users. No difference in the rate of odor formation was found when neutral pH (7.0) and acid pH (3.4) collagen sponges were tested, although we believe that a pH 3.4 is too acid and promotes odor formation. The optimal pH of the sponge should be 4.5 to 5.5. Malodor was efficiently extracted from sponges by washing in acid milieu of tap water and vinegar or 0.1 M acetate buffer, pH 4.0. Alkali extraction procedures were ineffective, and lukewarm water was slightly less effective than acid extraction of odor. At the time of malodor development, the high content of polyamines (putrescine, spermine, spermidine) in the ejaculate decreased to undetectable values. We conclude that the ejaculate is the major source of malodor formation in intravaginally worn collagen sponges. Removal, rinsing optimally in vinegar solution, and reinsertion within 24 hours after intercourse reduces the chance of malodor formation.", "contents": "Studies on vaginal malodor. I. Study in humans. Forty-two percent of collagen sponges tested as an intravaginal barrier contraceptive method developed malodor when retained for 5 days. Only 4% developed odor when the sponge was removed within 24 hours after intercourse, rinsed, and reinserted. While sexually active volunteers found odor in 37% of the sponges, odor formed only in 4% of the sponges worn by sexually inactive users. No difference in the rate of odor formation was found when neutral pH (7.0) and acid pH (3.4) collagen sponges were tested, although we believe that a pH 3.4 is too acid and promotes odor formation. The optimal pH of the sponge should be 4.5 to 5.5. Malodor was efficiently extracted from sponges by washing in acid milieu of tap water and vinegar or 0.1 M acetate buffer, pH 4.0. Alkali extraction procedures were ineffective, and lukewarm water was slightly less effective than acid extraction of odor. At the time of malodor development, the high content of polyamines (putrescine, spermine, spermidine) in the ejaculate decreased to undetectable values. We conclude that the ejaculate is the major source of malodor formation in intravaginally worn collagen sponges. Removal, rinsing optimally in vinegar solution, and reinsertion within 24 hours after intercourse reduces the chance of malodor formation."}
{"id": "PMID:28503", "title": "The uses of endodontic implant stabilizers in posttraumatic and periodontal disease.", "content": "Use of the endodontic implant stabilizer presents a sound physiologic procedure for stabilizing mobile teeth. It can increase root length, alter rootcrown ratios, immobilize fractured roots and periodontally compromised teeth, or supply combinations of these benefits. Case selection, operative technique, and case reports with follow-up are presented in order to demonstrate uses and versatility.", "contents": "The uses of endodontic implant stabilizers in posttraumatic and periodontal disease. Use of the endodontic implant stabilizer presents a sound physiologic procedure for stabilizing mobile teeth. It can increase root length, alter rootcrown ratios, immobilize fractured roots and periodontally compromised teeth, or supply combinations of these benefits. Case selection, operative technique, and case reports with follow-up are presented in order to demonstrate uses and versatility."}
{"id": "PMID:28507", "title": "Bromsulphthalein retention test and gamma-glutamyl transpeptidase activity in the investigation of liver disease.", "content": "The usefulness of serum gamma-glutamyl transpeptidase activity (gammaGT) was studied in 39 patients on whom a bromsulphthalein retention test (BSP) was performed. In most patients, the potentially hazardous BSP test did not give any further evidence of hepatic disease over conventional hepatic function tests and the gammaGT.", "contents": "Bromsulphthalein retention test and gamma-glutamyl transpeptidase activity in the investigation of liver disease. The usefulness of serum gamma-glutamyl transpeptidase activity (gammaGT) was studied in 39 patients on whom a bromsulphthalein retention test (BSP) was performed. In most patients, the potentially hazardous BSP test did not give any further evidence of hepatic disease over conventional hepatic function tests and the gammaGT."}
{"id": "PMID:28505", "title": "[Increased resistance of streptococcus pneumoniae to antibiotics and prevalence of their capsular serotypes (author's transl)].", "content": "From January 1970 to December 1976, 867 strains of Streptococcus pneumoniae isolated from clinical specimens were routinely typed and tested for sensitivity to 12 antibiotics. The prevalent serotypes were 19, 23, 6, 3, 7 and 14. Twenty seven p. cent of the strains were found resistant to tetracycline, and 4,2% were resistant to tetracycline and chloramphenicol. Two strains were resistant to erythromycin. The minimal inhibitory concentrations of penicillin G, cephalotin, chloramphenicol, tetracycline, minocycline and erythromycin were determined by the agar dilution method on 80 strains. The incidence of tetracycline resistant strains increased from 10% to 40%. These strains were less susceptible to minocycline when tested in vitro and they were clinically resistant. Chloramphenicol resistant strains are isolated since 1972 and represented in 1976 more than 6% of the isolates. They belong to 14 different serotypes. We have previously reported that resistance to chloramphenicol is due to a chloramphenicol-acetyl-transferase which is probably plasmid mediated. The epidemiological and clinical implications of these results are discussed.", "contents": "[Increased resistance of streptococcus pneumoniae to antibiotics and prevalence of their capsular serotypes (author's transl)]. From January 1970 to December 1976, 867 strains of Streptococcus pneumoniae isolated from clinical specimens were routinely typed and tested for sensitivity to 12 antibiotics. The prevalent serotypes were 19, 23, 6, 3, 7 and 14. Twenty seven p. cent of the strains were found resistant to tetracycline, and 4,2% were resistant to tetracycline and chloramphenicol. Two strains were resistant to erythromycin. The minimal inhibitory concentrations of penicillin G, cephalotin, chloramphenicol, tetracycline, minocycline and erythromycin were determined by the agar dilution method on 80 strains. The incidence of tetracycline resistant strains increased from 10% to 40%. These strains were less susceptible to minocycline when tested in vitro and they were clinically resistant. Chloramphenicol resistant strains are isolated since 1972 and represented in 1976 more than 6% of the isolates. They belong to 14 different serotypes. We have previously reported that resistance to chloramphenicol is due to a chloramphenicol-acetyl-transferase which is probably plasmid mediated. The epidemiological and clinical implications of these results are discussed."}
{"id": "PMID:28509", "title": "Increases of guanosine 3',5'-monophosphate-related enzymes in kidneys of developing rats.", "content": "Guanylate cyclase, cGMP phosphodiesterase and protein kinase activities were determined in kidneys of developing and adult rats. Guanylate cyclase activities of crude kidney homogenates, 100,000 x g supernatant and pellet of 7- and 21-day-old and adult rats were determined (Table I). In the kidneys of 7-day-old rats activity was 162% of adult controls in the homogenates (P less than .001), 144% in the soluble (P less than .005) and 308% in the particulate fraction (P less than .001). In 3-week-old rats activity was still significantly higher at 144% in the homogenate (P less than 0.02) and at 225% in the particulate (P less than .001). Phosphodiesterase activity for cGMP was 7488 +/- 831 pmol cGMP/mg protein . min in 1-week-old and 7674 +/- 1120 in 3-week-old rats vs. 4042 +/- 122 in the adults (P less than .025) (Table II). Chromatography on Sephadex G-200 showed two peaks of cGMP-stimulatable protein kinase in both the adult and newborn kidney and in addition a minor peak of cGMP-stimulatable kinase in the newborn kidny only (Fig. 2).", "contents": "Increases of guanosine 3',5'-monophosphate-related enzymes in kidneys of developing rats. Guanylate cyclase, cGMP phosphodiesterase and protein kinase activities were determined in kidneys of developing and adult rats. Guanylate cyclase activities of crude kidney homogenates, 100,000 x g supernatant and pellet of 7- and 21-day-old and adult rats were determined (Table I). In the kidneys of 7-day-old rats activity was 162% of adult controls in the homogenates (P less than .001), 144% in the soluble (P less than .005) and 308% in the particulate fraction (P less than .001). In 3-week-old rats activity was still significantly higher at 144% in the homogenate (P less than 0.02) and at 225% in the particulate (P less than .001). Phosphodiesterase activity for cGMP was 7488 +/- 831 pmol cGMP/mg protein . min in 1-week-old and 7674 +/- 1120 in 3-week-old rats vs. 4042 +/- 122 in the adults (P less than .025) (Table II). Chromatography on Sephadex G-200 showed two peaks of cGMP-stimulatable protein kinase in both the adult and newborn kidney and in addition a minor peak of cGMP-stimulatable kinase in the newborn kidny only (Fig. 2)."}
{"id": "PMID:28510", "title": "Fatal graft-versus-host disease after a small leukocyte transfusion in a patient with lymphoma and varicella.", "content": "A child with a poorly differentiated lymphoma developed varicella while being treated with maintenance chemotherapeutic agents. He received a transfusion of nonirradiated leukocytes from 1 unit of whole blood donated by a healthy volunteer who had recently recovered from varicella. The clinical course of varicella was aborted, but a classic graft-versus-host reaction developed and ultimately proved fatal. The host may have presented a large population of antigen-bearing cells to an infusion of presensitized immunocompetent donor cells, leading to an overwhelming aggressor lymphocyte reaction. We speculate that a modified approach using irradiated donor cells could be of benefit in the treatment of varicella infections in the immunosuppressed host.", "contents": "Fatal graft-versus-host disease after a small leukocyte transfusion in a patient with lymphoma and varicella. A child with a poorly differentiated lymphoma developed varicella while being treated with maintenance chemotherapeutic agents. He received a transfusion of nonirradiated leukocytes from 1 unit of whole blood donated by a healthy volunteer who had recently recovered from varicella. The clinical course of varicella was aborted, but a classic graft-versus-host reaction developed and ultimately proved fatal. The host may have presented a large population of antigen-bearing cells to an infusion of presensitized immunocompetent donor cells, leading to an overwhelming aggressor lymphocyte reaction. We speculate that a modified approach using irradiated donor cells could be of benefit in the treatment of varicella infections in the immunosuppressed host."}
{"id": "PMID:28512", "title": "Action and interaction of perivascular H+, K+ and Ca++ on pial arteries.", "content": "In cats the perivascular space of small pial arteries was perfused with mock CSF by means of micropipettes. Variations of K+, H+ and Ca++ activities in the perfusate cause changes of the diameters of the affected vessels. Increases of H+ and moderate increases of K+ lead to dilatations, Ca++ -increases elicit constrictions. The ions interact in such a way that perivascular Ca++ inhibits the K+ or H+ induced dilator response of the pial arteries. Alkalosis intensifies the constrictor action of Ca++. Perivascular microperfusion with Ca++ -free mock CSF causes dilatation which can be augmented by additional acidosis (pH 6.5). However, an increase of K+ to 10.8-10(-3) mol.1(-1) (4 times normal) does not change the diameters of the vessels already dilated, thus indicating differences in the action of K+ and H+ upon the membranes of the pial vascular smooth muscle cells. Small vessels (less than 80 micron diameter) respond with a significantly stronger dilatation when Ca++ is complexed with EGTA as compared with vessels of more than 80 micron diameter.", "contents": "Action and interaction of perivascular H+, K+ and Ca++ on pial arteries. In cats the perivascular space of small pial arteries was perfused with mock CSF by means of micropipettes. Variations of K+, H+ and Ca++ activities in the perfusate cause changes of the diameters of the affected vessels. Increases of H+ and moderate increases of K+ lead to dilatations, Ca++ -increases elicit constrictions. The ions interact in such a way that perivascular Ca++ inhibits the K+ or H+ induced dilator response of the pial arteries. Alkalosis intensifies the constrictor action of Ca++. Perivascular microperfusion with Ca++ -free mock CSF causes dilatation which can be augmented by additional acidosis (pH 6.5). However, an increase of K+ to 10.8-10(-3) mol.1(-1) (4 times normal) does not change the diameters of the vessels already dilated, thus indicating differences in the action of K+ and H+ upon the membranes of the pial vascular smooth muscle cells. Small vessels (less than 80 micron diameter) respond with a significantly stronger dilatation when Ca++ is complexed with EGTA as compared with vessels of more than 80 micron diameter."}
{"id": "PMID:28514", "title": "Effect of benzolamide on luminal pH in proximal convoluted tubules of the rat kidney.", "content": "Luminal pH in early and late proximal tubules was recorded continuously with antimony microelectrodes before and during carbonic anhydrase inhibition. Following i.v. application of benzolamide (25 mumol/kg BW), luminal pH decreased almost immediately in early proximal tubules (deltapH--0.42 +/- 0.06SEM), but increased in late proximal tubules (deltapH +0.27 +/- 0.06). Urinary pH increased (deltapH + 1.6 +/- 0.16) after a delay of some 30 s. Similar results, i.e. decrease of pH in early and increase of pH in late proximal tubules, were obtained, when benzolamide containing solutions were microinfused into early proximal tubules or superfused on the nephron surface. In contrast, luminal pH decreased in late proximal tubules, when benzolamide was microinfused into the same nephron segment. The decrease of luminal pH indicates inhibition of luminally active carbonic anhydrase, leading to delayed buffering  of secreted hydrogen ions. The increase of luminal pH in late proximal tubules may be attributed to several factors including increased delivery of bicarbonate, impaired bicarbonate exit at the antiluminal membrane and decreased hydrogen ion formation in the tubular cell due to inhibition of cellular carbonic anhydrase.", "contents": "Effect of benzolamide on luminal pH in proximal convoluted tubules of the rat kidney. Luminal pH in early and late proximal tubules was recorded continuously with antimony microelectrodes before and during carbonic anhydrase inhibition. Following i.v. application of benzolamide (25 mumol/kg BW), luminal pH decreased almost immediately in early proximal tubules (deltapH--0.42 +/- 0.06SEM), but increased in late proximal tubules (deltapH +0.27 +/- 0.06). Urinary pH increased (deltapH + 1.6 +/- 0.16) after a delay of some 30 s. Similar results, i.e. decrease of pH in early and increase of pH in late proximal tubules, were obtained, when benzolamide containing solutions were microinfused into early proximal tubules or superfused on the nephron surface. In contrast, luminal pH decreased in late proximal tubules, when benzolamide was microinfused into the same nephron segment. The decrease of luminal pH indicates inhibition of luminally active carbonic anhydrase, leading to delayed buffering  of secreted hydrogen ions. The increase of luminal pH in late proximal tubules may be attributed to several factors including increased delivery of bicarbonate, impaired bicarbonate exit at the antiluminal membrane and decreased hydrogen ion formation in the tubular cell due to inhibition of cellular carbonic anhydrase."}
{"id": "PMID:28516", "title": "Photodissociable dimer reduction products of 2-thiopyrimidine derivatives.", "content": "Both 4,6-dimethyl-2-thipyrimidine and its 1-methyl derivative undergo polarographic reduction in aqueous medium, via a 1e/1H+ reduction to a free radical which rapidly dimerizes to products isolates and identified as 4,4'-bis-(4,6-dimethyl-3,4-dihydropyrimidin-2-thione) and the corresponding 1-methyl dimer. The dimers may be oxidized electrolytically to regenerate the parent monomers. Both dimers also undergo photodissociation to quantitatively regenerate the parent monomers, in high quantum yield, 0.23 and 0.35 M/Einstein. The correlation between electrochemical and photochemical reductions of 2-thiopyrimidines are discussed, as well as the significance of the dimer photodissociation reactions in relation to nucleic acid photochemistry.", "contents": "Photodissociable dimer reduction products of 2-thiopyrimidine derivatives. Both 4,6-dimethyl-2-thipyrimidine and its 1-methyl derivative undergo polarographic reduction in aqueous medium, via a 1e/1H+ reduction to a free radical which rapidly dimerizes to products isolates and identified as 4,4'-bis-(4,6-dimethyl-3,4-dihydropyrimidin-2-thione) and the corresponding 1-methyl dimer. The dimers may be oxidized electrolytically to regenerate the parent monomers. Both dimers also undergo photodissociation to quantitatively regenerate the parent monomers, in high quantum yield, 0.23 and 0.35 M/Einstein. The correlation between electrochemical and photochemical reductions of 2-thiopyrimidines are discussed, as well as the significance of the dimer photodissociation reactions in relation to nucleic acid photochemistry."}
{"id": "PMID:28517", "title": "Skin closure with polyglycolic acid (Dexon).", "content": "Cosmetically satisfactory scars were achieved in 94.5% of skin crease orchidopexy wounds sutured with subcuticular polyglycolic acid. Of twenty-seven similar wounds closed with interrupted black silk sutures 18.5% developed hypertrophy at the medial end.", "contents": "Skin closure with polyglycolic acid (Dexon). Cosmetically satisfactory scars were achieved in 94.5% of skin crease orchidopexy wounds sutured with subcuticular polyglycolic acid. Of twenty-seven similar wounds closed with interrupted black silk sutures 18.5% developed hypertrophy at the medial end."}
{"id": "PMID:28520", "title": "Rat liver microsomal and lysosomal beta-glucuronidases differ in both carbohydrate and amino acid compositions.", "content": "To investigate the chemical relationships between rat liver lysosomal and microsomal beta-D-glucuronidases (EC 3.2.1.31), which are essentially identical catalytically and in reactivity with antibody and similar in molecular weight, the two enzymes were isolated by procedures in which modifications of the proteins were avoided. The purified enzymes were found to differ in both sugar and amino acid compositions. The microsomal enzyme contained much more mannose and, in contrast to the lysosomal enzyme, contained sialic acid but no glucose. Moreover, although the amino acid compositions generally agreed closely, the microsomal enzyme contained much more serine and somewhat less arginine than the lysosomal form. These findings of specific differences in composition should have a bearing on the consideration of intracellular glycoprotein synthesis, translocation, and compartmentalization.", "contents": "Rat liver microsomal and lysosomal beta-glucuronidases differ in both carbohydrate and amino acid compositions. To investigate the chemical relationships between rat liver lysosomal and microsomal beta-D-glucuronidases (EC 3.2.1.31), which are essentially identical catalytically and in reactivity with antibody and similar in molecular weight, the two enzymes were isolated by procedures in which modifications of the proteins were avoided. The purified enzymes were found to differ in both sugar and amino acid compositions. The microsomal enzyme contained much more mannose and, in contrast to the lysosomal enzyme, contained sialic acid but no glucose. Moreover, although the amino acid compositions generally agreed closely, the microsomal enzyme contained much more serine and somewhat less arginine than the lysosomal form. These findings of specific differences in composition should have a bearing on the consideration of intracellular glycoprotein synthesis, translocation, and compartmentalization."}
{"id": "PMID:28521", "title": "Demonstration of high-affinity folate binding activity associated with the brush border membranes of rat kidney.", "content": "Folate binding activity of high affinity was identified in the particulate fractions of rat kidney homogenates. This binding activity cofractionated with alkaline phosphatase and maltase, two brush border membranes markers. With an enriched preparation of brush border membranes, freed of endogenous folate by acid treatment, the binding of [3H]olate was found to be saturable (Kb = 4.2 X 10(-11)M) and rapid. Binding was optimal at pH 6.4-7.7. At neutral pH, competition for binding with [3H]folic acid required 1.45 equivalents of pteroylheptaglutamate, 6.25 equivalents of N5-methyltetrathydrofolate, 29 equivalents of methotrexate, and 125 equivalents of N5-formyltetrahydrofolate. At alkaline pH, N5-methyltetrahydrofolate was as effective a competitor as folic acid. In view of reports that renal tubular reabsorption of folate includes an initial tight binding step, the binding activity associated with the brush border membranes may participate in this process.", "contents": "Demonstration of high-affinity folate binding activity associated with the brush border membranes of rat kidney. Folate binding activity of high affinity was identified in the particulate fractions of rat kidney homogenates. This binding activity cofractionated with alkaline phosphatase and maltase, two brush border membranes markers. With an enriched preparation of brush border membranes, freed of endogenous folate by acid treatment, the binding of [3H]olate was found to be saturable (Kb = 4.2 X 10(-11)M) and rapid. Binding was optimal at pH 6.4-7.7. At neutral pH, competition for binding with [3H]folic acid required 1.45 equivalents of pteroylheptaglutamate, 6.25 equivalents of N5-methyltetrathydrofolate, 29 equivalents of methotrexate, and 125 equivalents of N5-formyltetrahydrofolate. At alkaline pH, N5-methyltetrahydrofolate was as effective a competitor as folic acid. In view of reports that renal tubular reabsorption of folate includes an initial tight binding step, the binding activity associated with the brush border membranes may participate in this process."}
{"id": "PMID:28522", "title": "Allosteric regulation of monocyclic interconvertible enzyme cascade systems: use of Escherichia coli glutamine synthetase as an experimental model.", "content": "The interconversion of Escherichia coli glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] between its adenylylated and unadenylylated forms has been used to verify the prediction derived from a theoretical analysis of the steady-state functions of a model for a monocyclic interconvertible enzyme cascade system [Stadtman, E. R. & Chock, P. B. (1977) Proc. Natl. Acad. Sci. USA 74, 2761-2770]. Because glutamine and alpha-ketoglutarate are multifunctional effectors and because three active enzyme complexes are involved in both adenylylation and deadenylylation of glutamine synthetase, at least 28 constants are required to describe the glutamine synthetase monocyclic cascade. Of these, 22 constants were determined experimentally and 6 were estimated via computer curve fitting. Despite the complexity, when both adenylylation and deadenylylation reactions are functioning, the number of adenylyl groups bound per mole of enzyme, n, assumes a steady-state level as is predicted by the model. This n value is determined by the mole fraction of P(IIA)-given by ([P(IIA)]/([P(IIA)] + [P(IID)])-and the ratio of glutamine to alpha-ketoglutarate (P(IID) and P(IID) are the unmodified and the uridylylated forms of the P(II) regulatory protein). In the presence of 0.5 mM glutamine and 2 mM alpha-ketoglutarate, the value of n increases as a nearly hyperbolic function in response to increasing mole fractions of P(IIA). When the constant level of alpha-ketoglutarate is gradually increased to 40 muM, the hyperbolic function converts slowly to a parabolic function. When the P(IIA) mole fraction was maintained at 0.6 and alpha-ketoglutarate levels were varied from 1 mM to 4 muM, an 800-fold increase in signal amplification was observed with respect to glutamine activation. In addition, because glutamine activates the adenylylation and inhibits the deadenylylation reaction, a sensitivity index of 2.1 (corresponding to a Hill number of 1.5) was obtained for the variation of n values in response to increasing glutamine concentration.", "contents": "Allosteric regulation of monocyclic interconvertible enzyme cascade systems: use of Escherichia coli glutamine synthetase as an experimental model. The interconversion of Escherichia coli glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] between its adenylylated and unadenylylated forms has been used to verify the prediction derived from a theoretical analysis of the steady-state functions of a model for a monocyclic interconvertible enzyme cascade system [Stadtman, E. R. & Chock, P. B. (1977) Proc. Natl. Acad. Sci. USA 74, 2761-2770]. Because glutamine and alpha-ketoglutarate are multifunctional effectors and because three active enzyme complexes are involved in both adenylylation and deadenylylation of glutamine synthetase, at least 28 constants are required to describe the glutamine synthetase monocyclic cascade. Of these, 22 constants were determined experimentally and 6 were estimated via computer curve fitting. Despite the complexity, when both adenylylation and deadenylylation reactions are functioning, the number of adenylyl groups bound per mole of enzyme, n, assumes a steady-state level as is predicted by the model. This n value is determined by the mole fraction of P(IIA)-given by ([P(IIA)]/([P(IIA)] + [P(IID)])-and the ratio of glutamine to alpha-ketoglutarate (P(IID) and P(IID) are the unmodified and the uridylylated forms of the P(II) regulatory protein). In the presence of 0.5 mM glutamine and 2 mM alpha-ketoglutarate, the value of n increases as a nearly hyperbolic function in response to increasing mole fractions of P(IIA). When the constant level of alpha-ketoglutarate is gradually increased to 40 muM, the hyperbolic function converts slowly to a parabolic function. When the P(IIA) mole fraction was maintained at 0.6 and alpha-ketoglutarate levels were varied from 1 mM to 4 muM, an 800-fold increase in signal amplification was observed with respect to glutamine activation. In addition, because glutamine activates the adenylylation and inhibits the deadenylylation reaction, a sensitivity index of 2.1 (corresponding to a Hill number of 1.5) was obtained for the variation of n values in response to increasing glutamine concentration."}
{"id": "PMID:28523", "title": "Interaction of methotrexate, folates, and pyridine nucleotides with dihydrofolate reductase: calorimetric and spectroscopic binding studies.", "content": "The thermodynamic parameters, deltaG, deltaH, and deltaS characterizing the tight binding of methotrexate, folates, and pyridine nucleotides to chicken liver dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) have been determined from calorimetric and fluorescence measurements. At 25 degrees the binding of NADPH and NADP+ is characterized by small negative enthalpies and large positive entropies whereas the binding of the folates and methotrexate is accompanied by large negative enthalpies and small negative entropies. In addition, the enthalpy of methotrexate-enzyme interaction demonstrates a proton transfer associated with binding; this is not the case with folate and dihydrofolate, thus confirming the conclusions drawn from the observed difference spectra characteristic of the interaction of methotrexate and substrates with the enzyme. The implications of these results are discussed in terms of the nature of the binding process, conformational changes in the enzyme, and the nature of the active site region.", "contents": "Interaction of methotrexate, folates, and pyridine nucleotides with dihydrofolate reductase: calorimetric and spectroscopic binding studies. The thermodynamic parameters, deltaG, deltaH, and deltaS characterizing the tight binding of methotrexate, folates, and pyridine nucleotides to chicken liver dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) have been determined from calorimetric and fluorescence measurements. At 25 degrees the binding of NADPH and NADP+ is characterized by small negative enthalpies and large positive entropies whereas the binding of the folates and methotrexate is accompanied by large negative enthalpies and small negative entropies. In addition, the enthalpy of methotrexate-enzyme interaction demonstrates a proton transfer associated with binding; this is not the case with folate and dihydrofolate, thus confirming the conclusions drawn from the observed difference spectra characteristic of the interaction of methotrexate and substrates with the enzyme. The implications of these results are discussed in terms of the nature of the binding process, conformational changes in the enzyme, and the nature of the active site region."}
{"id": "PMID:28524", "title": "Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents.", "content": "A quantitative method is described for the measurement of intralysosomal pH in living cells. Fluorescein isothiocyanate-labeled dextran (FD) is endocytized and accumulates in lysosomes where it remains without apparent degradation. The fluorescence spectrum of this compound changes with pH in the range 4-7 and is not seriously affected by FD concentration, ionic strength, or protein concentration. Living cells on coverslips are mounted in a spectrofluorometer cell and can be perfused with various media. The normal pH inside macrophage lysosomes seems to be 4.7-4.8, although it can drop transiently as low as 4.5. Exposure of the cells to various weak bases and to acidic potassium ionophores causes the pH to increase. The changes in pH are much more rapid than is the intralysosomal accumulation of the weak bases. Inhibitors of glycolysis (2-deoxyglucose) and of oxidative phosphorylation (cyanide or azide) added together, but not separately, cause the intralysosomal pH to increase. These results provide evidence for the existence of an active proton accumulation mechanism in the lysosomal membrane and support the theory of lysosomal accumulation of weak bases by proton trapping.", "contents": "Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. A quantitative method is described for the measurement of intralysosomal pH in living cells. Fluorescein isothiocyanate-labeled dextran (FD) is endocytized and accumulates in lysosomes where it remains without apparent degradation. The fluorescence spectrum of this compound changes with pH in the range 4-7 and is not seriously affected by FD concentration, ionic strength, or protein concentration. Living cells on coverslips are mounted in a spectrofluorometer cell and can be perfused with various media. The normal pH inside macrophage lysosomes seems to be 4.7-4.8, although it can drop transiently as low as 4.5. Exposure of the cells to various weak bases and to acidic potassium ionophores causes the pH to increase. The changes in pH are much more rapid than is the intralysosomal accumulation of the weak bases. Inhibitors of glycolysis (2-deoxyglucose) and of oxidative phosphorylation (cyanide or azide) added together, but not separately, cause the intralysosomal pH to increase. These results provide evidence for the existence of an active proton accumulation mechanism in the lysosomal membrane and support the theory of lysosomal accumulation of weak bases by proton trapping."}
{"id": "PMID:28525", "title": "Physicochemical characterization of six monoclonal cryoimmunoglobulins: possible basis for cold-dependent insolubility.", "content": "The physical and chemical properties of five human and one canine monoclonal cryoimmunoglobulin have been compared. By many criteria, the proteins cannot be distinguished from the noncryoglobulin reference proteins analyzed in parallel; however, certain hydrodynamic and spectroscopic properties of the proteins indicate that cryoimmunoglobulins differ in tertiary structure relative to their cold-soluble counterparts. These differences seem to favor low-temperature-induced association between cryoglobulin molecules as an immediate consequence of increased intermolecular ionic or van der Waals forces. No evidence was found for the formation of cold-dependent antigen-antibody complexes or the ubiquitous presence of low-temperature-dependent conformation changes as a component of cryoprecipitation. Rather, the anomalous solution behavior of monoclonal cryoimmunoglobulins can be considered a direct result of the individual solubility properties of these proteins.", "contents": "Physicochemical characterization of six monoclonal cryoimmunoglobulins: possible basis for cold-dependent insolubility. The physical and chemical properties of five human and one canine monoclonal cryoimmunoglobulin have been compared. By many criteria, the proteins cannot be distinguished from the noncryoglobulin reference proteins analyzed in parallel; however, certain hydrodynamic and spectroscopic properties of the proteins indicate that cryoimmunoglobulins differ in tertiary structure relative to their cold-soluble counterparts. These differences seem to favor low-temperature-induced association between cryoglobulin molecules as an immediate consequence of increased intermolecular ionic or van der Waals forces. No evidence was found for the formation of cold-dependent antigen-antibody complexes or the ubiquitous presence of low-temperature-dependent conformation changes as a component of cryoprecipitation. Rather, the anomalous solution behavior of monoclonal cryoimmunoglobulins can be considered a direct result of the individual solubility properties of these proteins."}
{"id": "PMID:28526", "title": "Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: impairment by glucocorticoids.", "content": "Addition of nerve growth factor to cultures of dissociated rat adrenal medullary cells caused fiber outgrowth from chromaffin cells. These fibers exhibited all the characteristics of neurites, particularly the formation of typical growth cones exhibiting intense catecholamine-specific fluorescence. Because this nerve growth factor-mediated neurite outgrowth could be abolished by physiological concentrations of glucocorticoids, it is concluded that the high glucocorticoid concentrations normally present in the adrenal medulla prevent the fiber outgrowth from medullary chromaffin cells in vivo. In dissociated sympathetic neurons the same concentrations of glucocorticoids markedly reduce but do not completely abolish neuronal fiber outgrowth.", "contents": "Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: impairment by glucocorticoids. Addition of nerve growth factor to cultures of dissociated rat adrenal medullary cells caused fiber outgrowth from chromaffin cells. These fibers exhibited all the characteristics of neurites, particularly the formation of typical growth cones exhibiting intense catecholamine-specific fluorescence. Because this nerve growth factor-mediated neurite outgrowth could be abolished by physiological concentrations of glucocorticoids, it is concluded that the high glucocorticoid concentrations normally present in the adrenal medulla prevent the fiber outgrowth from medullary chromaffin cells in vivo. In dissociated sympathetic neurons the same concentrations of glucocorticoids markedly reduce but do not completely abolish neuronal fiber outgrowth."}
{"id": "PMID:28527", "title": "Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica.", "content": "Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.", "contents": "Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica. Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions."}
{"id": "PMID:28534", "title": "Hydrolysis of cephalosporins in strongly acid medium.", "content": "The hydrolysis of cephalexin, cephalothin and cephaloridine in strongly acid medium (10--25% sulfuric acid) at high temperature (approximately 100 degrees C) was studied. The hydrolysis proceeds with a high rate (10--15 min are necessary for complete hydrolysis) and results in definite products with low mol.-wt. The hydrolysis under such hard conditions affects the side chain in 3-position, in some cases the C--N bond in the amido group in 7-position, and leads to a total cleavage of the beta-lactam ring, giving thiazine compounds. The reaction products were identified using IR and UV spectral data, thin-layer and gas chromatography, and some characteristic reactions of functional groups. The results of the investigation were used for development of photometric procedures for determination of cephalosporins.", "contents": "Hydrolysis of cephalosporins in strongly acid medium. The hydrolysis of cephalexin, cephalothin and cephaloridine in strongly acid medium (10--25% sulfuric acid) at high temperature (approximately 100 degrees C) was studied. The hydrolysis proceeds with a high rate (10--15 min are necessary for complete hydrolysis) and results in definite products with low mol.-wt. The hydrolysis under such hard conditions affects the side chain in 3-position, in some cases the C--N bond in the amido group in 7-position, and leads to a total cleavage of the beta-lactam ring, giving thiazine compounds. The reaction products were identified using IR and UV spectral data, thin-layer and gas chromatography, and some characteristic reactions of functional groups. The results of the investigation were used for development of photometric procedures for determination of cephalosporins."}
{"id": "PMID:28539", "title": "A study in mice of benzodiazephine-anticholinergic interaction: protection against restraint-immersion and forced exertion-induced gastric mucosal erosion.", "content": "The effectiveness of benzodiazepines and anticholinergics administered alone or in combination in preventing restraint-immersion and forced exertion-induced gastric mucosal erosion was investigated in mice. The benzodiazepines used were diazepam and chlordiazepoxide HCI and the anticholinergics were propantheline bromide and clidinium bromide. The administratio of a benzodiazepine with an anticholinergic resulted in additive or supra-additive protective effects in both systems. In the restraint-immersion system, diazepam combined with propantheline bromide at a ratio of 1 to 13.7 yielded a 4.53-fold supra-additive effect. At ratios of 4.6 or 1.5 parts of propantheline bromide to 1 part of diazepam an additive effect was observed. One part of diazepam, when combined with 1.4 to 12.0 parts of clidinium bromide resulted in supra-additive effects of about 1.5-fold. The co-administration of chlordiazepoxide HCI and clidinium bromide in ratios of 2 to 1 or 2.5 to 1 resulted in supra-additive effects of 2.4- and 1.85-fold, respectively. At higher and lower ratios additive effects were demonstrated. In the forced exertion system, diazepam combined with either anticholinergic resulted in supra-additive effects of 2- to 3-fold which occurred at ratios of diazepam to the anticholinergic varying over an 8-fold range. The co-administration of 2 parts of chlordiazepoxide HCI and 1 part of clidinium bromide resulted in a 2.84-fold supra-additive effect in the forced exertion system. These results are discussed in relation to the use of benzodiazepine anticholinergic combinations in the treatment of human gastric and duodenal ulcer disease.", "contents": "A study in mice of benzodiazephine-anticholinergic interaction: protection against restraint-immersion and forced exertion-induced gastric mucosal erosion. The effectiveness of benzodiazepines and anticholinergics administered alone or in combination in preventing restraint-immersion and forced exertion-induced gastric mucosal erosion was investigated in mice. The benzodiazepines used were diazepam and chlordiazepoxide HCI and the anticholinergics were propantheline bromide and clidinium bromide. The administratio of a benzodiazepine with an anticholinergic resulted in additive or supra-additive protective effects in both systems. In the restraint-immersion system, diazepam combined with propantheline bromide at a ratio of 1 to 13.7 yielded a 4.53-fold supra-additive effect. At ratios of 4.6 or 1.5 parts of propantheline bromide to 1 part of diazepam an additive effect was observed. One part of diazepam, when combined with 1.4 to 12.0 parts of clidinium bromide resulted in supra-additive effects of about 1.5-fold. The co-administration of chlordiazepoxide HCI and clidinium bromide in ratios of 2 to 1 or 2.5 to 1 resulted in supra-additive effects of 2.4- and 1.85-fold, respectively. At higher and lower ratios additive effects were demonstrated. In the forced exertion system, diazepam combined with either anticholinergic resulted in supra-additive effects of 2- to 3-fold which occurred at ratios of diazepam to the anticholinergic varying over an 8-fold range. The co-administration of 2 parts of chlordiazepoxide HCI and 1 part of clidinium bromide resulted in a 2.84-fold supra-additive effect in the forced exertion system. These results are discussed in relation to the use of benzodiazepine anticholinergic combinations in the treatment of human gastric and duodenal ulcer disease."}
{"id": "PMID:28544", "title": "Tardive dyskinesia and psychotropic drug history.", "content": "The adult population of a large mental hospital was screened for tardive dyskinesia (TD). Approximately 11% of the hospital population showed signs of TD; females and the elderly were over-represented in the TD group. A representative sample of those with TD was selected and a control (non-TD) patient was chosen to match each of the TD subjects in age, sex, length of hospitalization, diagnosis, and race. The charts of these subjects were searched for any indices of brain damage and the complete psychotropic medication history was recorded. There was no difference between the TD and controls in the amount of psychotropics ingested, in the duration of administration, in the kinds of drugs, or in the organicity history. Women as a group, however, tended to have more polypharmacy than men. The role of neuroleptics in TD is discussed as well as other possible etiological factors.", "contents": "Tardive dyskinesia and psychotropic drug history. The adult population of a large mental hospital was screened for tardive dyskinesia (TD). Approximately 11% of the hospital population showed signs of TD; females and the elderly were over-represented in the TD group. A representative sample of those with TD was selected and a control (non-TD) patient was chosen to match each of the TD subjects in age, sex, length of hospitalization, diagnosis, and race. The charts of these subjects were searched for any indices of brain damage and the complete psychotropic medication history was recorded. There was no difference between the TD and controls in the amount of psychotropics ingested, in the duration of administration, in the kinds of drugs, or in the organicity history. Women as a group, however, tended to have more polypharmacy than men. The role of neuroleptics in TD is discussed as well as other possible etiological factors."}
{"id": "PMID:28545", "title": "The effects of a new benzodiazepine derivative, ID-540, on the averaged photopalpebral reflex in man.", "content": "The effects of 7-chloro-5-(2-fluorophenyl)-1-methyl-1 H, 1.4-benzodiazepin-2(3H)-one (ID-540), a recently introduced benzodiazepine derivative, on the averaged photopalpebral reflex (PPR), subjective symptoms, and serum levels of ID-540 and its principal metabolite, N-desmethyl-ID-540, following an oral dose of 0.5 mg or placebo were investigated in six male Japanese students in a double-blind, crossover design. The peak latencies of PPR showed a statistically significant prolongation, with maximum level at 3 h after administration, which recovered to the initial level within 4 h. The amplitude of PPR failed to show a definite response to the drug. The serum concentration of ID-540 reached a peak level 2-3 h after administration, and then decreased at 4 h. N-Desmethyl-ID-540 exhibited a slow- gradual rise in serum. The latencies of PPR were positively correlated with the serum level of ID-540 but not with the N-desmethyl-ID-540. It is concluded that the PPR test may be a useful method for predicting the clinical effects of psychotropic drugs.", "contents": "The effects of a new benzodiazepine derivative, ID-540, on the averaged photopalpebral reflex in man. The effects of 7-chloro-5-(2-fluorophenyl)-1-methyl-1 H, 1.4-benzodiazepin-2(3H)-one (ID-540), a recently introduced benzodiazepine derivative, on the averaged photopalpebral reflex (PPR), subjective symptoms, and serum levels of ID-540 and its principal metabolite, N-desmethyl-ID-540, following an oral dose of 0.5 mg or placebo were investigated in six male Japanese students in a double-blind, crossover design. The peak latencies of PPR showed a statistically significant prolongation, with maximum level at 3 h after administration, which recovered to the initial level within 4 h. The amplitude of PPR failed to show a definite response to the drug. The serum concentration of ID-540 reached a peak level 2-3 h after administration, and then decreased at 4 h. N-Desmethyl-ID-540 exhibited a slow- gradual rise in serum. The latencies of PPR were positively correlated with the serum level of ID-540 but not with the N-desmethyl-ID-540. It is concluded that the PPR test may be a useful method for predicting the clinical effects of psychotropic drugs."}
{"id": "PMID:28546", "title": "Neuroleptic interference with the cocaine cue: internal stimulus control of behavior and psychosis.", "content": "The ability of cocaine to exert internal stimulus control of behavior was investigated by training rats to discriminate 10 mg/kg cocaine from saline in a discrete-trial, two-lever, food-reward procedure. Acquisition of response control by cocaine (1) succeeded in all animals tested, (2) proceeded rapidly, and (3) was associated with a high Commission Error: Omission Error ratio. These findings support the hypothesis that cocaine, a prototype of drugs inducing a psychotic condition in humans, can act as a powerful internal stimulus in rats. The cocaine cue was also responsive to the action of the dopamine-receptor-blocking agents spiperone (ED50: 0.06 mg/kg), haloperidol (0.24 mg/kg), and pimozide (1.90 mg/kg). d, l-Amphetamine (1.25 mg/kg) induced stimulus generalization with cocaine, and this generalization was blocked by dosages of the same neuroleptics comparable to those of cocaine antagonism. The results are discussed in terms of internal stimulus control of behavior and its relevance to the psychophysiology of schizophrenia.", "contents": "Neuroleptic interference with the cocaine cue: internal stimulus control of behavior and psychosis. The ability of cocaine to exert internal stimulus control of behavior was investigated by training rats to discriminate 10 mg/kg cocaine from saline in a discrete-trial, two-lever, food-reward procedure. Acquisition of response control by cocaine (1) succeeded in all animals tested, (2) proceeded rapidly, and (3) was associated with a high Commission Error: Omission Error ratio. These findings support the hypothesis that cocaine, a prototype of drugs inducing a psychotic condition in humans, can act as a powerful internal stimulus in rats. The cocaine cue was also responsive to the action of the dopamine-receptor-blocking agents spiperone (ED50: 0.06 mg/kg), haloperidol (0.24 mg/kg), and pimozide (1.90 mg/kg). d, l-Amphetamine (1.25 mg/kg) induced stimulus generalization with cocaine, and this generalization was blocked by dosages of the same neuroleptics comparable to those of cocaine antagonism. The results are discussed in terms of internal stimulus control of behavior and its relevance to the psychophysiology of schizophrenia."}
{"id": "PMID:28549", "title": "[The periarteritis nodosa--diagnosted by angiography. A case with multiple aneurysms (author's transl)].", "content": "Periarteritis nodosa is a severe systemic disease which is characterized by an inflammation of the vessel walls and a high incidence of renal involvement. Angiography should be performed immediately when clinical suspicion is aroused. Angiography is superior to the results of skin and muscles biopsy and gives information about the extension of the disease.", "contents": "[The periarteritis nodosa--diagnosted by angiography. A case with multiple aneurysms (author's transl)]. Periarteritis nodosa is a severe systemic disease which is characterized by an inflammation of the vessel walls and a high incidence of renal involvement. Angiography should be performed immediately when clinical suspicion is aroused. Angiography is superior to the results of skin and muscles biopsy and gives information about the extension of the disease."}
{"id": "PMID:28550", "title": "[Radiolytic decontamination of Di-n-butyl phthalate from water (author's transl)].", "content": "Recently, a considerable amount of phthalic acid esters (PAE), the most widely utilized plasticizer, has been released into and polluted the environment. Since their toxicity and teratogenicity, although fairly low, to experimental animals have recently been shown, the removal of them from the environment, especially from the drinking water, is desirable. As an attempt for the removal, the radiolytic degradation of 7-14C-di-n-butyl phthalate (14C-DBP) in water was investigated at several pHs. Approximately 50% of 14C-DBP (1 ppm aqueous solution) was decomposed by 60Co gamma-irradiation to a dose of 3 X 10(4) rad at pH 7 and the main product was mono-n-butyl phthalate (MBP). At pHs 3 and 11 14C-DBP was more easily radiolyzed and converted to ether-soluble compounds other than MBP or phthalic acid (PA). By irradiation to 10(6) rad 14C-DBP as well as 14C-MBP and 14C-PA, at pH value tested, was almost completely decomposed to volatile or water-soluble substances of possibly low molecular weight. These findings suggest that the gamma-irradiation is effective to make the PAE-polluted water clean.", "contents": "[Radiolytic decontamination of Di-n-butyl phthalate from water (author's transl)]. Recently, a considerable amount of phthalic acid esters (PAE), the most widely utilized plasticizer, has been released into and polluted the environment. Since their toxicity and teratogenicity, although fairly low, to experimental animals have recently been shown, the removal of them from the environment, especially from the drinking water, is desirable. As an attempt for the removal, the radiolytic degradation of 7-14C-di-n-butyl phthalate (14C-DBP) in water was investigated at several pHs. Approximately 50% of 14C-DBP (1 ppm aqueous solution) was decomposed by 60Co gamma-irradiation to a dose of 3 X 10(4) rad at pH 7 and the main product was mono-n-butyl phthalate (MBP). At pHs 3 and 11 14C-DBP was more easily radiolyzed and converted to ether-soluble compounds other than MBP or phthalic acid (PA). By irradiation to 10(6) rad 14C-DBP as well as 14C-MBP and 14C-PA, at pH value tested, was almost completely decomposed to volatile or water-soluble substances of possibly low molecular weight. These findings suggest that the gamma-irradiation is effective to make the PAE-polluted water clean."}
{"id": "PMID:28553", "title": "Rat brain gamma-glutamyl transpeptidase: effects of alcohol.", "content": "Adult rats were exposed to increasing air ethanol concentrations over a 12-day period without the use of pyrazole. Gamma-glutamyl transpeptidase levels were determined from various regions of rat brain. The enzyme levels in the pons-medulla, mid-brain and the striatum increased significantly during the 12-day exposure to ethanol. Other areas of the brain displayed a slight increase in enzyme activity, but not a significant level.", "contents": "Rat brain gamma-glutamyl transpeptidase: effects of alcohol. Adult rats were exposed to increasing air ethanol concentrations over a 12-day period without the use of pyrazole. Gamma-glutamyl transpeptidase levels were determined from various regions of rat brain. The enzyme levels in the pons-medulla, mid-brain and the striatum increased significantly during the 12-day exposure to ethanol. Other areas of the brain displayed a slight increase in enzyme activity, but not a significant level."}
{"id": "PMID:28554", "title": "Tyrosine hydroxylase activity in brain regions after intraventricular 6-hydroxydopamine in the neonatal rat.", "content": "Intraventricular 6-OHDA treatment to newborn rats produced a marked reduction in tyrosine hydroxylase activity in most brain regions at maturity which correlated moderately well with the catecholamine levels. However, those regions in which NE levels were increased did not show a corresponding increase in total tyrosine hydroxylase activity. There was a much better correlation between NE levels and the particulate form of tyrosine hydroxylase which has been suggested to be the more functionally active form of the enzyme.", "contents": "Tyrosine hydroxylase activity in brain regions after intraventricular 6-hydroxydopamine in the neonatal rat. Intraventricular 6-OHDA treatment to newborn rats produced a marked reduction in tyrosine hydroxylase activity in most brain regions at maturity which correlated moderately well with the catecholamine levels. However, those regions in which NE levels were increased did not show a corresponding increase in total tyrosine hydroxylase activity. There was a much better correlation between NE levels and the particulate form of tyrosine hydroxylase which has been suggested to be the more functionally active form of the enzyme."}
{"id": "PMID:28555", "title": "Effect of benzodiazepines on age of vaginal perforation and first estrus in mice.", "content": "Female mice which received chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, or nitrazepam prenatally and postnatally had delays in the age of vaginal perforation and first estrus concomitant with reduced postnatal growth. Females exposed prenatally showed no growth deficits, but in four treatments had delayed vaginal opening. However, the age of first estrus was generally less than the control.", "contents": "Effect of benzodiazepines on age of vaginal perforation and first estrus in mice. Female mice which received chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, or nitrazepam prenatally and postnatally had delays in the age of vaginal perforation and first estrus concomitant with reduced postnatal growth. Females exposed prenatally showed no growth deficits, but in four treatments had delayed vaginal opening. However, the age of first estrus was generally less than the control."}
{"id": "PMID:28556", "title": "Histamine receptors of airway smooth muscle of ferret and rat.", "content": "Ferret trachea and bronchus contract to carbachol greater than 5-HT greater than bradykinin (BK) greater than PGF2alpha greater than histamine greater than 2-methylhistamine (2-MeH: a specific H1-receptor agonist). Rat trachea is insensitive to the spasmogenic actions of histamine, 2-MeH, PGF2alpha, BK and 5-HT. Ferret trachea and bronchus and rat trachea (which were partially contracted to carbachol) relax to isoproterenol greater than PGE1 greater than E2 greater than 4-methyl-histamine (4-MeH: a specific H2-histamine receptor agonist). High doses of histamine also relax rat trachea. The contractions of ferret airways to 2-MeH coupled with the antagonism of histamine-induced contractions by mepyramine showed the presence of H1-histamine receptors in the trachea and bronchus of ferret. After H1-blockade, the relaxant responses to histamine on ferret bronchus and trachea, and rat trachea were not affecte by \"specific\" doses of burimamide, metiamide, and cimetidine (H2-receptor antagonists), indomethacin (PG-synthetase inhibitor) and propranolol (a beta-adrenoceptor blocker). These results appear to suggest the existence of an atypical histamine receptor subtype (i.e. not of the classical H1 or H2 type) in the airways of rat and ferret.", "contents": "Histamine receptors of airway smooth muscle of ferret and rat. Ferret trachea and bronchus contract to carbachol greater than 5-HT greater than bradykinin (BK) greater than PGF2alpha greater than histamine greater than 2-methylhistamine (2-MeH: a specific H1-receptor agonist). Rat trachea is insensitive to the spasmogenic actions of histamine, 2-MeH, PGF2alpha, BK and 5-HT. Ferret trachea and bronchus and rat trachea (which were partially contracted to carbachol) relax to isoproterenol greater than PGE1 greater than E2 greater than 4-methyl-histamine (4-MeH: a specific H2-histamine receptor agonist). High doses of histamine also relax rat trachea. The contractions of ferret airways to 2-MeH coupled with the antagonism of histamine-induced contractions by mepyramine showed the presence of H1-histamine receptors in the trachea and bronchus of ferret. After H1-blockade, the relaxant responses to histamine on ferret bronchus and trachea, and rat trachea were not affecte by \"specific\" doses of burimamide, metiamide, and cimetidine (H2-receptor antagonists), indomethacin (PG-synthetase inhibitor) and propranolol (a beta-adrenoceptor blocker). These results appear to suggest the existence of an atypical histamine receptor subtype (i.e. not of the classical H1 or H2 type) in the airways of rat and ferret."}
{"id": "PMID:28559", "title": "The heart production in energy-depleted human erythrocytes induced by glucose, inosine and adenine.", "content": "The heat production (HP) of glucose deprived human red blood cells was measured, using glucose, adenine and inosine as substrates. Inosine induced a significantly higher HP than glucose and adenine induced no significant HP. At low pH the HP of glucose decreased more than that of inosine, corresponding to an equally lowered lactate production. The results indicate that it should be possible to use the system developed to study the functional state both of the complete glycolytic system and the lower part of it in intact red blood cells during various clinical conditions.", "contents": "The heart production in energy-depleted human erythrocytes induced by glucose, inosine and adenine. The heat production (HP) of glucose deprived human red blood cells was measured, using glucose, adenine and inosine as substrates. Inosine induced a significantly higher HP than glucose and adenine induced no significant HP. At low pH the HP of glucose decreased more than that of inosine, corresponding to an equally lowered lactate production. The results indicate that it should be possible to use the system developed to study the functional state both of the complete glycolytic system and the lower part of it in intact red blood cells during various clinical conditions."}
{"id": "PMID:28561", "title": "beta-lactamases in bacteroides.", "content": "Bacteroides fragilis is responsible for most anaerobic infections in man. Most isolates of B. fragilis show resistance to beta-lactam antibiotics. This resistance might be due to beta-lactamase production or permeability barrier in the cell wall. B. fragilis produce beta-lactamase with mainly cephalosporinase activity. Other Bacteroides species such as B. clostridiformis, B. melaninogenicus and B. oralis also produce beta-lactamase but with different biochemical characteristics.", "contents": "beta-lactamases in bacteroides. Bacteroides fragilis is responsible for most anaerobic infections in man. Most isolates of B. fragilis show resistance to beta-lactam antibiotics. This resistance might be due to beta-lactamase production or permeability barrier in the cell wall. B. fragilis produce beta-lactamase with mainly cephalosporinase activity. Other Bacteroides species such as B. clostridiformis, B. melaninogenicus and B. oralis also produce beta-lactamase but with different biochemical characteristics."}
{"id": "PMID:28565", "title": "[The mucocutaneous and lymph node syndrome of Kawasaki. 1 case complicated by multiple aneurysms].", "content": "We report in a five month old baby a case of the cutaneomucosal and lymph node syndrome described by Kawasaki, remarkable for the onset of multiple aneurysms involving the coronary and the limb arteries. This syndrome has rarely been observed except in Japan where it seems frequent. Possibly is benign forms, without heart complications, producing a picture of febrile erythema of viral type, have not received sufficient attention. The relationship between Kawasaki's disease and periarteritis nodosa in infants is then discussed. The clinical and pathological existence of the fatal forms seems undoubted, but the generally benign course of Kawasaki's disease contrasts with the severe course of polyarteritis nodosa in infants. It is possible that the usually benign forms of Kawasaki's disease represent only the initial stage of periarteritis nodosa in infants, from which they may recover, and we have only identified until now the severe forms which are rapidly fatal. The etiology of Kawasaki's syndrome, like periateritis nodosa remains unknown.", "contents": "[The mucocutaneous and lymph node syndrome of Kawasaki. 1 case complicated by multiple aneurysms]. We report in a five month old baby a case of the cutaneomucosal and lymph node syndrome described by Kawasaki, remarkable for the onset of multiple aneurysms involving the coronary and the limb arteries. This syndrome has rarely been observed except in Japan where it seems frequent. Possibly is benign forms, without heart complications, producing a picture of febrile erythema of viral type, have not received sufficient attention. The relationship between Kawasaki's disease and periarteritis nodosa in infants is then discussed. The clinical and pathological existence of the fatal forms seems undoubted, but the generally benign course of Kawasaki's disease contrasts with the severe course of polyarteritis nodosa in infants. It is possible that the usually benign forms of Kawasaki's disease represent only the initial stage of periarteritis nodosa in infants, from which they may recover, and we have only identified until now the severe forms which are rapidly fatal. The etiology of Kawasaki's syndrome, like periateritis nodosa remains unknown."}
{"id": "PMID:28568", "title": "Granulomatous hepatitis associated with salicylazosulfapyridine therapy.", "content": "Granulomatous hepatitis has been associated with many conditions, including chronic ulcerative colitis and sulfonamide therapy. We report a patient with ulcerative colitis in whom hepatic granulomatosis was associated with salicylazosulfapyridine (Azulfidine). Sulfonamides should be considered a possible cause of hepatotoxicity when used therapeutically in inflammatory bowel disease.", "contents": "Granulomatous hepatitis associated with salicylazosulfapyridine therapy. Granulomatous hepatitis has been associated with many conditions, including chronic ulcerative colitis and sulfonamide therapy. We report a patient with ulcerative colitis in whom hepatic granulomatosis was associated with salicylazosulfapyridine (Azulfidine). Sulfonamides should be considered a possible cause of hepatotoxicity when used therapeutically in inflammatory bowel disease."}
{"id": "PMID:28592", "title": "Histopathology of hepatic acute graft-versus-host disease in the dog. A double blind study confirms the specificity of small bile duct lesions.", "content": "To test the association of small bile duct destructive lesions in the liver with acute graft-versus-host disease,  a blind (coded) histological study was done comparing liver tissue from three groups of dogs given 1,200 R of total-body irradiation: one not given marrow infusions after irradiation, another given autologous hemopoietic grafts, and a third given marrow grafts from DLA-nonidentical unrelated donors. The dogs with unrelated grafts all developed graft-versus-host disease, and their liver histology was distinguished from that of the dogs in the other two groups by three findings: (1) extensive small bile ductule necrosis and atypia; (2) infiltrates of mononuclear cells around and in ductules; and (3) individual hepatocyte necrosis scattered throughout the lobules. Thus, bile duct lesions appear to be a good marker for assessing the presence and severity of hepatic graft-versus-host disease in dogs.", "contents": "Histopathology of hepatic acute graft-versus-host disease in the dog. A double blind study confirms the specificity of small bile duct lesions. To test the association of small bile duct destructive lesions in the liver with acute graft-versus-host disease,  a blind (coded) histological study was done comparing liver tissue from three groups of dogs given 1,200 R of total-body irradiation: one not given marrow infusions after irradiation, another given autologous hemopoietic grafts, and a third given marrow grafts from DLA-nonidentical unrelated donors. The dogs with unrelated grafts all developed graft-versus-host disease, and their liver histology was distinguished from that of the dogs in the other two groups by three findings: (1) extensive small bile ductule necrosis and atypia; (2) infiltrates of mononuclear cells around and in ductules; and (3) individual hepatocyte necrosis scattered throughout the lobules. Thus, bile duct lesions appear to be a good marker for assessing the presence and severity of hepatic graft-versus-host disease in dogs."}
{"id": "PMID:28593", "title": "[Activity of NADP-dependent glycerol-3-phosphate dehydrogenase in skeletal muscles of animals].", "content": "The NADP-dependent glycerol-3-phosphate dehydrogenase activity was studied in sketetal muscles of the rat, rabbit and frog. The dehydrogenase activity in the skeletal muscles of the rat and rabbit was higher than that of the frog. The enzyme activity was found to depend upon the buffer, being higher in tris-HCl buffer than in triethanolamine buffer.", "contents": "[Activity of NADP-dependent glycerol-3-phosphate dehydrogenase in skeletal muscles of animals]. The NADP-dependent glycerol-3-phosphate dehydrogenase activity was studied in sketetal muscles of the rat, rabbit and frog. The dehydrogenase activity in the skeletal muscles of the rat and rabbit was higher than that of the frog. The enzyme activity was found to depend upon the buffer, being higher in tris-HCl buffer than in triethanolamine buffer."}
{"id": "PMID:28600", "title": "Megalourethra.", "content": "Two cases of megalourethra are presented, the ninth and tenth cases to be documented in the literature. Both patients exhibited mesodermal abnormalities which justify categorization among the minor forms of prune belly syndrome. One patient, the youngest to have undergone surgical correction, presented with azotemia, dilated posterior urethra, megacystis, and megaureters. The second patient with incomplete or scaphoid form of megalourethra also exhibited undescended testis, corrected by orchiopexy at the time of urethoplasty. In all instances the goal of treatment is preservation of renal function with subsequent functional and anatomic reconstruction of the urinary tract.", "contents": "Megalourethra. Two cases of megalourethra are presented, the ninth and tenth cases to be documented in the literature. Both patients exhibited mesodermal abnormalities which justify categorization among the minor forms of prune belly syndrome. One patient, the youngest to have undergone surgical correction, presented with azotemia, dilated posterior urethra, megacystis, and megaureters. The second patient with incomplete or scaphoid form of megalourethra also exhibited undescended testis, corrected by orchiopexy at the time of urethoplasty. In all instances the goal of treatment is preservation of renal function with subsequent functional and anatomic reconstruction of the urinary tract."}
{"id": "PMID:28601", "title": "Crossed renal ectopia with familial occurrence.", "content": "A familial occurrence of crossed renal ectopia is presented. No genetic factor has been determined in this congenital anomaly so this familial occurrence is believed to be incidental.", "contents": "Crossed renal ectopia with familial occurrence. A familial occurrence of crossed renal ectopia is presented. No genetic factor has been determined in this congenital anomaly so this familial occurrence is believed to be incidental."}
{"id": "PMID:28602", "title": "True prostatic tissue in 46,XX female with adrenogenital syndrome.", "content": "A case is presented of a seventeen-year-old phenotypic male with empty scrotum, hormonal studies consistent with adrenogenital syndrome, a 46,XX karyotype, and a normal prostate on rectal examination. Histochemical evidence of the true nature of the prostatic tissue is presented, and the developmental aspects of the case are discussed.", "contents": "True prostatic tissue in 46,XX female with adrenogenital syndrome. A case is presented of a seventeen-year-old phenotypic male with empty scrotum, hormonal studies consistent with adrenogenital syndrome, a 46,XX karyotype, and a normal prostate on rectal examination. Histochemical evidence of the true nature of the prostatic tissue is presented, and the developmental aspects of the case are discussed."}
{"id": "PMID:28610", "title": "[An inverse reaction of the ST-T complex in the elctrocardiogram due to beta receptor inhibition].", "content": "In this article shall be referred to a special form of reaction of the ST-T-complexes in the propranolol test. Instead of a normalisation of this section of the ECG an inverse reaction develops. It consists in the fact that after application of propranolol the negativities of the T-waves increase and the lowerings of the ST-distances deepen. They appear most frequently after an acute heart attack, such as after a spontaneous angina pectoris, and they can be reproduced only during some days. It is supposed that the cooperation of acute ischaemic myocardial processes with negative sequelae of the blockade of beta-receptors are responsible for this inverse reaction.", "contents": "[An inverse reaction of the ST-T complex in the elctrocardiogram due to beta receptor inhibition]. In this article shall be referred to a special form of reaction of the ST-T-complexes in the propranolol test. Instead of a normalisation of this section of the ECG an inverse reaction develops. It consists in the fact that after application of propranolol the negativities of the T-waves increase and the lowerings of the ST-distances deepen. They appear most frequently after an acute heart attack, such as after a spontaneous angina pectoris, and they can be reproduced only during some days. It is supposed that the cooperation of acute ischaemic myocardial processes with negative sequelae of the blockade of beta-receptors are responsible for this inverse reaction."}
{"id": "PMID:28611", "title": "[Empirical examination of training programs for the treatment of speech anxiety].", "content": "This study is the result of an attempt to get effective methods in order to reduce the students' speaking anxiety in seminars. In a prepost-design, two training programs are compared: systematic desensitization and assertive training. Success is controlled with the help of a subjective anxiety scale, the \"Freiburger Pers\u00f6nlichkeitsinventar\" (FPI), and by scanning how often and how long somebody is speaking in a seminar. The main results are: both of the training programs reduce speaking anxiety signficantly (perhaps with a little more success of SD), SD also reduces \"Gehemmtheit\" (FPI-Scale 8). There is a lot of difficulties with regard to the observation of the behavior variables but it seems to be that Ass increases speaking frequency in relation to the groups' mean, while this effect could not be supposed according to SD. At the end of the article, the results are discussed and some questions are raised with regard to the further research of training programs.", "contents": "[Empirical examination of training programs for the treatment of speech anxiety]. This study is the result of an attempt to get effective methods in order to reduce the students' speaking anxiety in seminars. In a prepost-design, two training programs are compared: systematic desensitization and assertive training. Success is controlled with the help of a subjective anxiety scale, the \"Freiburger Pers\u00f6nlichkeitsinventar\" (FPI), and by scanning how often and how long somebody is speaking in a seminar. The main results are: both of the training programs reduce speaking anxiety signficantly (perhaps with a little more success of SD), SD also reduces \"Gehemmtheit\" (FPI-Scale 8). There is a lot of difficulties with regard to the observation of the behavior variables but it seems to be that Ass increases speaking frequency in relation to the groups' mean, while this effect could not be supposed according to SD. At the end of the article, the results are discussed and some questions are raised with regard to the further research of training programs."}
{"id": "PMID:28607", "title": "[Pancreatic exocrine secretion to the introduction into the blood of amino acid mixtures of varying composition].", "content": "Tests conducted on dogs with a fistula of the pancreatic duct evidenced that various amino acids mixtures containing all the essential amino acids and differing mainly in the replaceable nitrogen dissimilarly act on the external secretion of the pancreas after their introduction into the blood. The most intensive secretion produces a mixture in which the replaceable nitrogen is represented by glycine alone. The mixture, one of its constituent is one of the dicarboxylic acids (glutamic) very poorly stimulates this function. At the same time, the action of all the studied amino acids mixtures is less pronounced than is the effect of the caseine hydrolysate. The commercial agent aminofusin L-600, containing all the essential amino acids with addition of polyols (xylitol and sorbitol) with no dicarboxylic amino acids in its composition, produces an intensive pancreatic secretion close to that caused by the caseine hydrolysate.", "contents": "[Pancreatic exocrine secretion to the introduction into the blood of amino acid mixtures of varying composition]. Tests conducted on dogs with a fistula of the pancreatic duct evidenced that various amino acids mixtures containing all the essential amino acids and differing mainly in the replaceable nitrogen dissimilarly act on the external secretion of the pancreas after their introduction into the blood. The most intensive secretion produces a mixture in which the replaceable nitrogen is represented by glycine alone. The mixture, one of its constituent is one of the dicarboxylic acids (glutamic) very poorly stimulates this function. At the same time, the action of all the studied amino acids mixtures is less pronounced than is the effect of the caseine hydrolysate. The commercial agent aminofusin L-600, containing all the essential amino acids with addition of polyols (xylitol and sorbitol) with no dicarboxylic amino acids in its composition, produces an intensive pancreatic secretion close to that caused by the caseine hydrolysate."}
{"id": "PMID:28609", "title": "Phenobarbital increases spontaneous transmitter release at the frog neuromuscular junction.", "content": "Phenobarbital (1-2 \u00d7 10(-4)M) markedly increases the frequency of miniature end-plate potentials at the neuromuscular synapse of the frog. This effect was seen in calcium free media containing EGTA. The drug probably acts presynaptically at an intracellular locus to increase the presynaptic free calcium concentration.", "contents": "Phenobarbital increases spontaneous transmitter release at the frog neuromuscular junction. Phenobarbital (1-2 \u00d7 10(-4)M) markedly increases the frequency of miniature end-plate potentials at the neuromuscular synapse of the frog. This effect was seen in calcium free media containing EGTA. The drug probably acts presynaptically at an intracellular locus to increase the presynaptic free calcium concentration."}
{"id": "PMID:28615", "title": "Influence of sodium tripolyphosphate and citric acid on the shelf life of thornback ray (Raja clavata L.).", "content": "Sodium tripolyphosphate dips (5 min in 12% solution) extended shelf life of thornback ray wings by about 2 days, improved the appearance and eliminated weight losses. With citric acid dips (5 min in 0.5% solution) a 3 day extension of storage life was obtained but the treatment had a slight bleaching effect and caused weight losses of about 5%. Both compounds were effective in retarding the breakdown of urea with formation of ammonia in thorback ray.", "contents": "Influence of sodium tripolyphosphate and citric acid on the shelf life of thornback ray (Raja clavata L.). Sodium tripolyphosphate dips (5 min in 12% solution) extended shelf life of thornback ray wings by about 2 days, improved the appearance and eliminated weight losses. With citric acid dips (5 min in 0.5% solution) a 3 day extension of storage life was obtained but the treatment had a slight bleaching effect and caused weight losses of about 5%. Both compounds were effective in retarding the breakdown of urea with formation of ammonia in thorback ray."}
{"id": "PMID:28618", "title": "[Post mortem determination of bromureides (author's transl)].", "content": "Concentrations of carbromal, carbromide and bromisoval are determined in blood, urine, brain, kidney and muscle taken at autopsy from 41 fatal cases after overdosage of bromureides. In addition values of total bromine in blood are presented. Contents of total bromine can only lead to the deduction that a chronical abuse of bromureides is existent or not. Concentrations of bromureides and carbromide show a wide range according to the different time between taking the drug and death particularly in cases of pure carbromal intoxications which sometimes cause death after several days. In such cases quantitative determination of carbromide, a pharmacologically active metabolite of carbromal, is the only way to prove an acute carbromal intoxication. Especially in cases of additional foreign substances death may occur in early the phase of poisoning. Bromureides decompose post mortem by putrefaction a high degree so that the condition of the cadaver is important. Brain tissue is the most usable material for examination but other organs, particularly muscle and kidney, can be analysed with success. For differential diagnosis fatal cases are presented which were not caused by drug intake.", "contents": "[Post mortem determination of bromureides (author's transl)]. Concentrations of carbromal, carbromide and bromisoval are determined in blood, urine, brain, kidney and muscle taken at autopsy from 41 fatal cases after overdosage of bromureides. In addition values of total bromine in blood are presented. Contents of total bromine can only lead to the deduction that a chronical abuse of bromureides is existent or not. Concentrations of bromureides and carbromide show a wide range according to the different time between taking the drug and death particularly in cases of pure carbromal intoxications which sometimes cause death after several days. In such cases quantitative determination of carbromide, a pharmacologically active metabolite of carbromal, is the only way to prove an acute carbromal intoxication. Especially in cases of additional foreign substances death may occur in early the phase of poisoning. Bromureides decompose post mortem by putrefaction a high degree so that the condition of the cadaver is important. Brain tissue is the most usable material for examination but other organs, particularly muscle and kidney, can be analysed with success. For differential diagnosis fatal cases are presented which were not caused by drug intake."}
{"id": "PMID:28620", "title": "Utilization of industrial and agricultural by-products for fungal amylase production.", "content": "Attempts were made for using industrial and agricultural by-products and wastes as carbon and nitrogen sources in fermentation medium for alpha-amylase production by Aspergillus niger NRRL-337. The original carbon source of the basal medium was replaced by one of the following materials: rice bran, wheat bran, corn bran, corn starch, cane molasses, and glucose syrup. Rice bran proved to be the best carbon source that secured the highest amylase activity. The nitrogen source of the basal medium was then replaced by different cheap materials, viz: dried yeast, corn steep liquor, gluten-30, gluten-50, and corn steep precipitate. Corn steep precipitate proved to be superior in amylase production. In consideration of these results an economical medium that secured high activity, containing the following ingredients, was suggested: 2.5% corn steep precipitate, 7.2% rice bran, 0.1% MgSO4, 0.1% KH2PO4, and 0.1% CaCO3. From this medium fungal amylase was precipitated and purified. The pure enzyme gave the highest activity at 40 degrees C and pH 4.3.", "contents": "Utilization of industrial and agricultural by-products for fungal amylase production. Attempts were made for using industrial and agricultural by-products and wastes as carbon and nitrogen sources in fermentation medium for alpha-amylase production by Aspergillus niger NRRL-337. The original carbon source of the basal medium was replaced by one of the following materials: rice bran, wheat bran, corn bran, corn starch, cane molasses, and glucose syrup. Rice bran proved to be the best carbon source that secured the highest amylase activity. The nitrogen source of the basal medium was then replaced by different cheap materials, viz: dried yeast, corn steep liquor, gluten-30, gluten-50, and corn steep precipitate. Corn steep precipitate proved to be superior in amylase production. In consideration of these results an economical medium that secured high activity, containing the following ingredients, was suggested: 2.5% corn steep precipitate, 7.2% rice bran, 0.1% MgSO4, 0.1% KH2PO4, and 0.1% CaCO3. From this medium fungal amylase was precipitated and purified. The pure enzyme gave the highest activity at 40 degrees C and pH 4.3."}
{"id": "PMID:28624", "title": "[Experiences with continuous fetal measurements during pregnancy].", "content": "Experiences by continuous ultrasonic measurements during pregnancy. The authors have published earlier a diagram for use to evaluate the fetal development. The aptitude in practice has been proved.--To evaluate normal fetal growth the percentiles curves of Lubchenco are less suitable than of the GDR. But also the last show the normal weight 100 to 150 g to small during the 30th to 36th gestation week in comparison to the calculated fetal weight of normal pregnancies. The intrauterine retardation and hypertrophy can well be diagnosed if the beginning of the measures occurs at the end of the first trimenon of the pregnancy. But it is necessary to know the possibilities of apparent \"abnormalities\" in normal pregnancy, as ceccation of the fetal growth for 3 or 4 weeks, the late flattening of the biparietal diameter in breech presentation etc.--Our effort to simulatae the fetal growth in intrauterine retardation by using beta-stimulating sympathicomimetics, was without of success.", "contents": "[Experiences with continuous fetal measurements during pregnancy]. Experiences by continuous ultrasonic measurements during pregnancy. The authors have published earlier a diagram for use to evaluate the fetal development. The aptitude in practice has been proved.--To evaluate normal fetal growth the percentiles curves of Lubchenco are less suitable than of the GDR. But also the last show the normal weight 100 to 150 g to small during the 30th to 36th gestation week in comparison to the calculated fetal weight of normal pregnancies. The intrauterine retardation and hypertrophy can well be diagnosed if the beginning of the measures occurs at the end of the first trimenon of the pregnancy. But it is necessary to know the possibilities of apparent \"abnormalities\" in normal pregnancy, as ceccation of the fetal growth for 3 or 4 weeks, the late flattening of the biparietal diameter in breech presentation etc.--Our effort to simulatae the fetal growth in intrauterine retardation by using beta-stimulating sympathicomimetics, was without of success."}
{"id": "PMID:28619", "title": "[Benorylate and indomethacin in cervical syndromes: a comparative double-blind study].", "content": "In a double-blind study the effectiveness of benorylate and indomethacin was compared in patients suffering from cervical spine syndromes. From a total of 60 patients, 30 individuals (group A) received 100 mg of indomethacin/day and 30 (group B) were treated with 6 g of benorylate per day. Clinical improvement as judged by several given criteria occurred in 80% of the patients in group A and in 76.7% of the patients in group B. If strict objective criteria (ie. increased mobility) were used, 53.3% improved in both groups, while subjective criteria revealed improvement in 76.7% in both groups. Neurological signs improved in 36.7% in group A and in 30% in group B. In two patients treatment with indomethacin was discontinued because of severe side effects. In the benorylate treated group 3 patients had to be taken off treatment for the same reason. Side effects were mainly gastro-intestinal. The study indicates that with regard to clinical effectiveness benorylate is comparable to indomethacin in patients suffering from cervical spine syndromes; the substance is cheap and relatively tolerable.", "contents": "[Benorylate and indomethacin in cervical syndromes: a comparative double-blind study]. In a double-blind study the effectiveness of benorylate and indomethacin was compared in patients suffering from cervical spine syndromes. From a total of 60 patients, 30 individuals (group A) received 100 mg of indomethacin/day and 30 (group B) were treated with 6 g of benorylate per day. Clinical improvement as judged by several given criteria occurred in 80% of the patients in group A and in 76.7% of the patients in group B. If strict objective criteria (ie. increased mobility) were used, 53.3% improved in both groups, while subjective criteria revealed improvement in 76.7% in both groups. Neurological signs improved in 36.7% in group A and in 30% in group B. In two patients treatment with indomethacin was discontinued because of severe side effects. In the benorylate treated group 3 patients had to be taken off treatment for the same reason. Side effects were mainly gastro-intestinal. The study indicates that with regard to clinical effectiveness benorylate is comparable to indomethacin in patients suffering from cervical spine syndromes; the substance is cheap and relatively tolerable."}
{"id": "PMID:28625", "title": "[Significance of a general umbilical-cord pH for the evaluation of acidosis morbidity].", "content": "The value of a general pH analysis of the artery umbilicalis as a parameter of the postnatal diagnostic of the newborns is shown. The classification of the values in different grades of acidity and the relation to the Apgar score show, that the light and middle-heavy acidoses are not determined sufficiently by the Apgar score. The CTG-monitoring and the stimulation of the Oxytocin had no influence on the frequency of the different grades of the acidity. The meaning of the general blood-gas analysis in the artery umbilicalis for the morbidity of acidity and the check of the obstetrical activity of the clinic is shown.", "contents": "[Significance of a general umbilical-cord pH for the evaluation of acidosis morbidity]. The value of a general pH analysis of the artery umbilicalis as a parameter of the postnatal diagnostic of the newborns is shown. The classification of the values in different grades of acidity and the relation to the Apgar score show, that the light and middle-heavy acidoses are not determined sufficiently by the Apgar score. The CTG-monitoring and the stimulation of the Oxytocin had no influence on the frequency of the different grades of the acidity. The meaning of the general blood-gas analysis in the artery umbilicalis for the morbidity of acidity and the check of the obstetrical activity of the clinic is shown."}
{"id": "PMID:28628", "title": "[In vitro effect of psychopharmacologic drugs on the embryonic brain tissue of the fetuses of schizophrenic mothers].", "content": "The author studied the influence on the adaptation of the nervous tissue explantations from 25 fetuses of schizophrenic mothers and a similar amount of fetuses from normal women (embryonal development--7-12 weeks) during the initial period of explantation in vitro (5-6 days) with 10 psychopharmacological preparations (aminasine, majeptile, stelasine, triphtasine, tesercin, theralen, haloperidol, eglonyl, mellipramin, seduxen). Their final concentration in a nourishing medium was approximately the same as in the blood of schizophrenic patients, treated by phenothiasine preparations. The adaptation of the fetus pervous tissue from schizophrenic mothers differed from the corresponding reaction of fetus brain explantation from normal women. There was a tendency to a higher stability of experimental cultures. However, there were differences depending upon the character of introduced drugs.", "contents": "[In vitro effect of psychopharmacologic drugs on the embryonic brain tissue of the fetuses of schizophrenic mothers]. The author studied the influence on the adaptation of the nervous tissue explantations from 25 fetuses of schizophrenic mothers and a similar amount of fetuses from normal women (embryonal development--7-12 weeks) during the initial period of explantation in vitro (5-6 days) with 10 psychopharmacological preparations (aminasine, majeptile, stelasine, triphtasine, tesercin, theralen, haloperidol, eglonyl, mellipramin, seduxen). Their final concentration in a nourishing medium was approximately the same as in the blood of schizophrenic patients, treated by phenothiasine preparations. The adaptation of the fetus pervous tissue from schizophrenic mothers differed from the corresponding reaction of fetus brain explantation from normal women. There was a tendency to a higher stability of experimental cultures. However, there were differences depending upon the character of introduced drugs."}
{"id": "PMID:28629", "title": "Regulation of anaerobic glycolysis in Ehrlich ascites tumour cells.", "content": "1) In intact Ehrlich ascites tumour cells the anaerobic glycolytic flux rate and pattern of intermediates have been investigated at different pH values of the extracellular medium. 2) As predicted from the dependence of the lactic acid dehydrogenase equilibrium on pH a strong negative correlation between log ([lactate]/[pyruvate]) and pH has been found. 3) The steady state fluxes of glycolysis at pH 8.0 and 7.4 are rather equal, despite significant differences in the intracellular concentrations of glycolytic intermediates. At pH 8.0 the concentrations of ATP, glucose 6-phosphate, and fructose 6-phosphate are lower, and the concentrations of ADP, AMP, fructose 1,6-bisphosphate, triose phosphates, phosphoglycerates, and phosphoenolpyruvate are higher than at pH 7.4. 4) From the analysis of the pH dependent changes of metabolites it follows that different mechanisms are responsible for maintaining equal actual activities of hexokinase, phosphofructokinase and pyruvate kinase at pH 7.4 and 8.0. 5) From an application of the linear theory of enzymatic chains and a calculation of the control strength of the regulatory important enzymes results that hexokinase is evidently rate-limiting for glycolysis, and phosphofructokinase is also significantly influencing the glycolytic flux. Pyruvate kinase and glyceraldehyde phosphate dehydrogenase, on the other hand, do not significantly affect the rate of the overall glycolytic flux in ascites.", "contents": "Regulation of anaerobic glycolysis in Ehrlich ascites tumour cells. 1) In intact Ehrlich ascites tumour cells the anaerobic glycolytic flux rate and pattern of intermediates have been investigated at different pH values of the extracellular medium. 2) As predicted from the dependence of the lactic acid dehydrogenase equilibrium on pH a strong negative correlation between log ([lactate]/[pyruvate]) and pH has been found. 3) The steady state fluxes of glycolysis at pH 8.0 and 7.4 are rather equal, despite significant differences in the intracellular concentrations of glycolytic intermediates. At pH 8.0 the concentrations of ATP, glucose 6-phosphate, and fructose 6-phosphate are lower, and the concentrations of ADP, AMP, fructose 1,6-bisphosphate, triose phosphates, phosphoglycerates, and phosphoenolpyruvate are higher than at pH 7.4. 4) From the analysis of the pH dependent changes of metabolites it follows that different mechanisms are responsible for maintaining equal actual activities of hexokinase, phosphofructokinase and pyruvate kinase at pH 7.4 and 8.0. 5) From an application of the linear theory of enzymatic chains and a calculation of the control strength of the regulatory important enzymes results that hexokinase is evidently rate-limiting for glycolysis, and phosphofructokinase is also significantly influencing the glycolytic flux. Pyruvate kinase and glyceraldehyde phosphate dehydrogenase, on the other hand, do not significantly affect the rate of the overall glycolytic flux in ascites."}
{"id": "PMID:28630", "title": "The haemodynamic effects of sodium nitroprusside-induced hypotension during beta-adrenergic blockade and anaesthesia. A case report.", "content": "We present the central haemodynamic data obtained during halothane/nitrous oxide anaesthesia in a patient under antihypertensive treatment with propranolol who underwent surgery for intracranial aneurysms in sodium nitroprusside-induced hypotension. Cardiac output remained unchanged when hypotension was induced. Pulmonary capillary wedge pressure decreased. There was a slight increase in heart rate, as well as a minor decrease in stroke volume. Systemic vascular resistance decreased, but pulmonary vascular resistance remained unchanged. The response observed is discussed.", "contents": "The haemodynamic effects of sodium nitroprusside-induced hypotension during beta-adrenergic blockade and anaesthesia. A case report. We present the central haemodynamic data obtained during halothane/nitrous oxide anaesthesia in a patient under antihypertensive treatment with propranolol who underwent surgery for intracranial aneurysms in sodium nitroprusside-induced hypotension. Cardiac output remained unchanged when hypotension was induced. Pulmonary capillary wedge pressure decreased. There was a slight increase in heart rate, as well as a minor decrease in stroke volume. Systemic vascular resistance decreased, but pulmonary vascular resistance remained unchanged. The response observed is discussed."}
{"id": "PMID:28631", "title": "Accuracy and reproducibility of arterial blood-gas and pH measurements.", "content": "In 30 patients blood samples were taken from both radial arteries and analysed for PCO2, PO2 and pH. The influence of sampling technique on the accuracy of blood-gas analysis was determined. The 95% confidence limits for PCO2 measurements were +/-0.32 kPa (2.4 mmHg), and for PO2 measurements were +/-1.16 kPa (8.8 mmHg) in the range below 20 kPa, and +/-2.94 kPa (22.0 mmHg) above 20 kPa. For pH, the 95% confidence limits were +/-0.014. Only the PO2 measurements were significantly influenced by the sampling procedure.", "contents": "Accuracy and reproducibility of arterial blood-gas and pH measurements. In 30 patients blood samples were taken from both radial arteries and analysed for PCO2, PO2 and pH. The influence of sampling technique on the accuracy of blood-gas analysis was determined. The 95% confidence limits for PCO2 measurements were +/-0.32 kPa (2.4 mmHg), and for PO2 measurements were +/-1.16 kPa (8.8 mmHg) in the range below 20 kPa, and +/-2.94 kPa (22.0 mmHg) above 20 kPa. For pH, the 95% confidence limits were +/-0.014. Only the PO2 measurements were significantly influenced by the sampling procedure."}
{"id": "PMID:28632", "title": "Porphyrin biosynthesis. Immobilized enzymes and ligands. VII. Studies on bovine liver porphobilinogenase.", "content": "Bovine liver porphobilinogenase (PBGase) has been covalently attached to Sepharose, and some of their properties have been studied. The optimal conditions for binding have been determined. The water-insoluble PBGase retained a high percentage of the activity of the soluble enzyme; the coupling yield was also high. Sepharose-PBGase could be stored at 4 C for periods up to 5 weeks with 40% loss of activity; however, both by storage and repeated use, isomerase was inactivated and the percentage of uroporphyrinogen I formed was increased. Attachment of PBGase to Sepharose has led to enhanced thermal stability. pH optima of the insolubilized enzyme was shifted 0.6 units towards the alkaline side as compared to that of the native enzyme.", "contents": "Porphyrin biosynthesis. Immobilized enzymes and ligands. VII. Studies on bovine liver porphobilinogenase. Bovine liver porphobilinogenase (PBGase) has been covalently attached to Sepharose, and some of their properties have been studied. The optimal conditions for binding have been determined. The water-insoluble PBGase retained a high percentage of the activity of the soluble enzyme; the coupling yield was also high. Sepharose-PBGase could be stored at 4 C for periods up to 5 weeks with 40% loss of activity; however, both by storage and repeated use, isomerase was inactivated and the percentage of uroporphyrinogen I formed was increased. Attachment of PBGase to Sepharose has led to enhanced thermal stability. pH optima of the insolubilized enzyme was shifted 0.6 units towards the alkaline side as compared to that of the native enzyme."}
{"id": "PMID:28633", "title": "Dependence of starch synthase activity from maize leaves on light, pH and redox state.", "content": "The starch synthase activity of bundle sheath cells of maize leaves is very low in darkened plants and increases on illumination. In order to find an explanation of these facts we subjected leaf strips, isolated bundle sheath cells and enzymic preparations to pH-changes and to oxidizing or reducing substances. We found that the increase of the activity produced by light could also be caused in the leaf strips by adding malate to the suspending fluid in the dark. On the contrary, with isolated bundle sheath cells no increase with light or with the addition of malate could be observed. There was a decrease of activity due to acidification or to the addition of dichlorophenol-indophenol (DCPIP). The same effect could be observed with enzymic preparations as with the isolated bundle sheath cells, whereas the decrease of activity was higher by acidification of samples coming from darkened plants than for those enzymes prepared from illuminated plants. Also other substances inhibited the synthase activity: benzoquinone, DOPA, caffeic acid, TMPD or Fe (CN6) 3- and PCMB, while only DTE could increase it. After preincubation with PCMB the enzyme activity could be restored with DTE, not so for the preincubation with DCPIP. With an enzymic preparation that contained intact organelles the increase of activity could also be produced by NADH. Thus we follow that the decrease of synthase activity in the darkened plants is due to acidification and to the presence of oxidizing substances, too.", "contents": "Dependence of starch synthase activity from maize leaves on light, pH and redox state. The starch synthase activity of bundle sheath cells of maize leaves is very low in darkened plants and increases on illumination. In order to find an explanation of these facts we subjected leaf strips, isolated bundle sheath cells and enzymic preparations to pH-changes and to oxidizing or reducing substances. We found that the increase of the activity produced by light could also be caused in the leaf strips by adding malate to the suspending fluid in the dark. On the contrary, with isolated bundle sheath cells no increase with light or with the addition of malate could be observed. There was a decrease of activity due to acidification or to the addition of dichlorophenol-indophenol (DCPIP). The same effect could be observed with enzymic preparations as with the isolated bundle sheath cells, whereas the decrease of activity was higher by acidification of samples coming from darkened plants than for those enzymes prepared from illuminated plants. Also other substances inhibited the synthase activity: benzoquinone, DOPA, caffeic acid, TMPD or Fe (CN6) 3- and PCMB, while only DTE could increase it. After preincubation with PCMB the enzyme activity could be restored with DTE, not so for the preincubation with DCPIP. With an enzymic preparation that contained intact organelles the increase of activity could also be produced by NADH. Thus we follow that the decrease of synthase activity in the darkened plants is due to acidification and to the presence of oxidizing substances, too."}
{"id": "PMID:28634", "title": "Correction of severe metabolic acidosis: a physiological approach.", "content": "1 - Five patients with severe metabolic acidosis secondary to methanol poisoning were studied before and after receiving 6.7 to 10 mEq NaHCO3/kg body weight. 2 - Two thirds of the infused HCO3- left the extracellular space and, since its apparent volume of distribution was much larger than under normal conditions, it largely overestimated HCO3- needs. On the contrary, the volume of distribution of the buffer base excess was found to be more stable and little affected by the acid-base status. 3 - Based on these observations, a simple method for estimating HCO3- needs in severe metabolic acidosis is proposed, requiring only the initial excess buffer base space which is calculated from body weight and blood buffer base excess values obtained before and after a first dose of bicarbonate.", "contents": "Correction of severe metabolic acidosis: a physiological approach. 1 - Five patients with severe metabolic acidosis secondary to methanol poisoning were studied before and after receiving 6.7 to 10 mEq NaHCO3/kg body weight. 2 - Two thirds of the infused HCO3- left the extracellular space and, since its apparent volume of distribution was much larger than under normal conditions, it largely overestimated HCO3- needs. On the contrary, the volume of distribution of the buffer base excess was found to be more stable and little affected by the acid-base status. 3 - Based on these observations, a simple method for estimating HCO3- needs in severe metabolic acidosis is proposed, requiring only the initial excess buffer base space which is calculated from body weight and blood buffer base excess values obtained before and after a first dose of bicarbonate."}
{"id": "PMID:28635", "title": "Effects of ethylephrine on the rat atrial pacemaker.", "content": "Ethylephrine, assayed in isolated rat atria, as a dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Yet, on the same basis, it was less powerful than epinephrine, norepinephrine or isoproterenol. Pretreatment with reserpine provoked supersensitivity and increase in the maximum. As well, previous administration of pargyline to the animals resulted in augmented accelerating effects, either in normal or reserpinized preparations. Cocaine or phentolamine shifted the dose-response curve to the left. On the contrary, propranolol, produced a marked action, decelerating the effects of ethylephrine and also decreased the maxima with higher doses. It is concluded that ethylephrine: a) is a direct-acting sympathomimetic amine; b) it brings beta-receptor stimulation; c) a certain degree of alpha-receptor decelerating effect is also involved; d) it is a good substrate of monoaminoxidase.", "contents": "Effects of ethylephrine on the rat atrial pacemaker. Ethylephrine, assayed in isolated rat atria, as a dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Yet, on the same basis, it was less powerful than epinephrine, norepinephrine or isoproterenol. Pretreatment with reserpine provoked supersensitivity and increase in the maximum. As well, previous administration of pargyline to the animals resulted in augmented accelerating effects, either in normal or reserpinized preparations. Cocaine or phentolamine shifted the dose-response curve to the left. On the contrary, propranolol, produced a marked action, decelerating the effects of ethylephrine and also decreased the maxima with higher doses. It is concluded that ethylephrine: a) is a direct-acting sympathomimetic amine; b) it brings beta-receptor stimulation; c) a certain degree of alpha-receptor decelerating effect is also involved; d) it is a good substrate of monoaminoxidase."}
{"id": "PMID:28636", "title": "[Effects of emetine and ipecacuana on dopamine central mechanisms. A pilot study].", "content": "The lack of any rotational behaviour in unilaterally dopamine lesioned animals after ipecacuana or emetine is a strong indication that these substances lack dopamine receptor stimulating properties when administered systematically. Our results thus support those of Lal et al. (1972). Our results do not allow any conclusions concerning the working mechanism of emetine. However, the lack of central dopamine receptor stimulating properties should probably not be explained by an inability to enter through the blood brain barrier but rather a lack of effect on dopamine receptors. This reasoning  would also exclude the dopamine receptors in the chemo-trigger zone as responsible for the emetic effect. In terms of the clinical usage of ipecacuana it seems highly improbable that this usage may cause adverse psychotic like side effects due to stimulation of central dopamine receptors.", "contents": "[Effects of emetine and ipecacuana on dopamine central mechanisms. A pilot study]. The lack of any rotational behaviour in unilaterally dopamine lesioned animals after ipecacuana or emetine is a strong indication that these substances lack dopamine receptor stimulating properties when administered systematically. Our results thus support those of Lal et al. (1972). Our results do not allow any conclusions concerning the working mechanism of emetine. However, the lack of central dopamine receptor stimulating properties should probably not be explained by an inability to enter through the blood brain barrier but rather a lack of effect on dopamine receptors. This reasoning  would also exclude the dopamine receptors in the chemo-trigger zone as responsible for the emetic effect. In terms of the clinical usage of ipecacuana it seems highly improbable that this usage may cause adverse psychotic like side effects due to stimulation of central dopamine receptors."}
{"id": "PMID:28650", "title": "Salazopyrin in rheumatoid arthritis.", "content": "After a 12-week preliminary period of observation 32 patients with consistently active rheumatoid arthritis (RA) were treated for up to 22 weeks with salazopyrin. Seven patients could not tolerate the drug. The remaining 25 patients had a marked improvement in subjective clinical state and significant falls in serum C-reactive protein and the erythrocyte sedimentation rate 6 weeks after treatment began. The improvement was maintained after 22 weeks. The results strongly suggest that further trials with this drug in RA are needed.", "contents": "Salazopyrin in rheumatoid arthritis. After a 12-week preliminary period of observation 32 patients with consistently active rheumatoid arthritis (RA) were treated for up to 22 weeks with salazopyrin. Seven patients could not tolerate the drug. The remaining 25 patients had a marked improvement in subjective clinical state and significant falls in serum C-reactive protein and the erythrocyte sedimentation rate 6 weeks after treatment began. The improvement was maintained after 22 weeks. The results strongly suggest that further trials with this drug in RA are needed."}
{"id": "PMID:28651", "title": "[Seroepidemiological investigations in domestic ruminants from Egypt, Somalia and Jordan for the demonstration of complement fixing antibodies against Rickettsia and Chlamydia (author's transl)].", "content": "1450 random serum samples of domestic ruminants from Egypt, Somalia and Jordan were investigated for complement fixing antibodies against Rickettsia and Chlamydia. Between 1.5 and 3.4% of the samples from the animals investigated had antibodies against the RMSF-group of Rickettsia, with exception of the sera from Somalian cattle and sheep from Jordan. Antibodies against Rickettsia of the Typhus-group were found in 4 cattle and 1 goat from Jordan and 2 sheep from Egypt; by agglutination test with type-specific antigen they were identified as antibodies against R. typhi. Using 2 different antigens, antibodies against Coxiella burnetii were found in every population tested. The prevalence was 2.0 to 12.2%, with the exception of cattle in Somalia, where only 1 positive serum (0.2%) was found. 27% of the serum samples from Jordan and 22% from Egypt but none of the 802 samples from Somalia had antibodies against Chlamydia. The results are discussed under an epidemiological point of view.", "contents": "[Seroepidemiological investigations in domestic ruminants from Egypt, Somalia and Jordan for the demonstration of complement fixing antibodies against Rickettsia and Chlamydia (author's transl)]. 1450 random serum samples of domestic ruminants from Egypt, Somalia and Jordan were investigated for complement fixing antibodies against Rickettsia and Chlamydia. Between 1.5 and 3.4% of the samples from the animals investigated had antibodies against the RMSF-group of Rickettsia, with exception of the sera from Somalian cattle and sheep from Jordan. Antibodies against Rickettsia of the Typhus-group were found in 4 cattle and 1 goat from Jordan and 2 sheep from Egypt; by agglutination test with type-specific antigen they were identified as antibodies against R. typhi. Using 2 different antigens, antibodies against Coxiella burnetii were found in every population tested. The prevalence was 2.0 to 12.2%, with the exception of cattle in Somalia, where only 1 positive serum (0.2%) was found. 27% of the serum samples from Jordan and 22% from Egypt but none of the 802 samples from Somalia had antibodies against Chlamydia. The results are discussed under an epidemiological point of view."}
{"id": "PMID:28652", "title": "Concanavalin a receptors on the cell membrane of Trypanosoma cruzi.", "content": "Epimastigotes and trypomastigotes of T. cruzi obtained from acellular culture as well as bloodstream trypomastigotes agglutinate with concanavalin A (Con A). Con A-binding sites were also localized on the cell membrane by using the Con A-horseradish peroxidase-diaminobenzidine method. Passage of epimastigotes and trypomastigotes from acellular culture through DEAE-cellulose column did not affect Con A-binding sites as detected by agglutination and electron miscroscopy.", "contents": "Concanavalin a receptors on the cell membrane of Trypanosoma cruzi. Epimastigotes and trypomastigotes of T. cruzi obtained from acellular culture as well as bloodstream trypomastigotes agglutinate with concanavalin A (Con A). Con A-binding sites were also localized on the cell membrane by using the Con A-horseradish peroxidase-diaminobenzidine method. Passage of epimastigotes and trypomastigotes from acellular culture through DEAE-cellulose column did not affect Con A-binding sites as detected by agglutination and electron miscroscopy."}
{"id": "PMID:28653", "title": "Electron microscopic studies on the development of kinetes of Theileria parva Theiler, 1904 in the gut of the vector ticks Rhipicephalus appendiculatus Neumann, 1901.", "content": "The development of motile stages, called kinetes, from a stationary stage (regarded as zygote) has been followed in Theileria parva by means of electron miscroscopy. This process started after moult of the tick nymphs which had sucked on highly infected calves, i.e. about 20 days after repletion (a.r.) of the ticks. The transformation took place by formation of a growing protrusion (= anlage) into an inner, enlarging vacuole. During this process the limiting membrane of the enlarging vacuole serves as the outer membrane of the developing motile stage, whereas the two inner ones as well as the subpellicular microtubules are newly formed. This transformation proceeds rapidly, so that on the 25th day a.r. most of the kinetes have already left the gut cells and started penetration into the salivary gland cells. On the way to the salivary glands nuclear divisions occurred within the kinetes. The steps of the transformation described were compared to those in T. annulata and to ookinete formation in haemosporidia.", "contents": "Electron microscopic studies on the development of kinetes of Theileria parva Theiler, 1904 in the gut of the vector ticks Rhipicephalus appendiculatus Neumann, 1901. The development of motile stages, called kinetes, from a stationary stage (regarded as zygote) has been followed in Theileria parva by means of electron miscroscopy. This process started after moult of the tick nymphs which had sucked on highly infected calves, i.e. about 20 days after repletion (a.r.) of the ticks. The transformation took place by formation of a growing protrusion (= anlage) into an inner, enlarging vacuole. During this process the limiting membrane of the enlarging vacuole serves as the outer membrane of the developing motile stage, whereas the two inner ones as well as the subpellicular microtubules are newly formed. This transformation proceeds rapidly, so that on the 25th day a.r. most of the kinetes have already left the gut cells and started penetration into the salivary gland cells. On the way to the salivary glands nuclear divisions occurred within the kinetes. The steps of the transformation described were compared to those in T. annulata and to ookinete formation in haemosporidia."}
{"id": "PMID:28654", "title": "Studies on Dipetalonema viteae (Filarioidea) I. Microfilaraemia in hamsters in relation to worm burden and humoral immune response.", "content": "The course of a primary infection with Dipetalonema viteae was studied in one randomly bred and in one inbred strain of hamster. Worm recovery and the duration and intensity of the microfilaraemia were analyzed and related to the humoral immune response of the host by using the indirect immunofluorescent antibody test on frozen sections of female worms, on eggs and on intact microfilariae. The inbred strain showed a greater susceptibility to the parasite. This was evidenced by high worm recovery and prolonged microfilaraemia. The duration of microfilaraemia did not depend on the number of recovered female worms. Most of the randomly bred hamsters suppressed microfilaraemia by week 30 post infection whereas some hamsters of the inbred strain were still microfilaraemic. Splenectomy prior to infection did not affect the duration of microfilaraemia. Antibodies to the cuticle of microfilariae always appeared in the sera after immunity to circulating microfilariae had been built up.", "contents": "Studies on Dipetalonema viteae (Filarioidea) I. Microfilaraemia in hamsters in relation to worm burden and humoral immune response. The course of a primary infection with Dipetalonema viteae was studied in one randomly bred and in one inbred strain of hamster. Worm recovery and the duration and intensity of the microfilaraemia were analyzed and related to the humoral immune response of the host by using the indirect immunofluorescent antibody test on frozen sections of female worms, on eggs and on intact microfilariae. The inbred strain showed a greater susceptibility to the parasite. This was evidenced by high worm recovery and prolonged microfilaraemia. The duration of microfilaraemia did not depend on the number of recovered female worms. Most of the randomly bred hamsters suppressed microfilaraemia by week 30 post infection whereas some hamsters of the inbred strain were still microfilaraemic. Splenectomy prior to infection did not affect the duration of microfilaraemia. Antibodies to the cuticle of microfilariae always appeared in the sera after immunity to circulating microfilariae had been built up."}
{"id": "PMID:28655", "title": "Studies on Dipetalonema vitae (Filarioidea). II. Antibody dependent adhesion of peritoneal exudate cells to microfilariae in vitro.", "content": "Peritoneal exudate cells from normal uninfected hamsters adhered in vitro to microfilariae in the presence of 19S antibody fractions from hamsters which had suppressed or were going to suppress their microfilaremia. The adhering cells were predominantly mononuclear, although eosinophils were occasionally found. Experiments with sensitized microfilariae and peritoneal exudate cells indicated that the macrophage probably recognizes the microfilariae/antibody complex. Macrophage cytophilic antibodies did not seem to be involved. This adhesion reaction may initiate the trapping of microfilariae in vivo, thus contributing to the observed acquired immunity to circulating microfilariae in the hamster.", "contents": "Studies on Dipetalonema vitae (Filarioidea). II. Antibody dependent adhesion of peritoneal exudate cells to microfilariae in vitro. Peritoneal exudate cells from normal uninfected hamsters adhered in vitro to microfilariae in the presence of 19S antibody fractions from hamsters which had suppressed or were going to suppress their microfilaremia. The adhering cells were predominantly mononuclear, although eosinophils were occasionally found. Experiments with sensitized microfilariae and peritoneal exudate cells indicated that the macrophage probably recognizes the microfilariae/antibody complex. Macrophage cytophilic antibodies did not seem to be involved. This adhesion reaction may initiate the trapping of microfilariae in vivo, thus contributing to the observed acquired immunity to circulating microfilariae in the hamster."}
{"id": "PMID:28656", "title": "[A contribution to the biology of Dicrocoelium hospes Looss, 1907 (Trematoda, Dicrocoeliidae)].", "content": "In this study, carried out in the Ivory Coast, Dicrocoelium hospes Looss, 1907 was shown for the first time to be a parasite of cattle and it was also detected in sheep by the presence of ova in the faeces. Up to 50% of the sheep in some flocks were found to shed eggs. The adults, sporocysts, \"slime balls\" and cercariae of D. hospes are described and compared to the respective stages of D. dendriticum. This comparison shows that essential morphological structures are very similar, especially the sensory papillae, which as so called chaetotaxis can serve to distinguish closely related species. The cercariae develop in terrestrial snails of the genus Limicolaria of which several species may play a role (L. flammea, L. felina, L. kambeul). The main habitat of D. hospes seems to be limited to savannah environment; only once could D. hospes be found in the borderzone between savannah and the rain forest. Infected Limicolaria-snails shed the cercariae in amorphous \"slime balls\" of liquid-jelly-like consistency and yellowish colour. Under the influence of sunlight these liquify; the cercariae, however, can survive for up to 26 h. According to our present knowledge the sunlight seems to be a factor which triggers the shedding of slime balls. This begins shortly after sunrise at a temperature of 22 degrees C and a relative humidity of 100%. Infected snails can shed cercariae on seven consecutive days. This kind of slime ball production might provide a clue to the 2nd intermediate host; efforts to identify this host have, however, so far been fruitless, despite the fact that almost 4000 arthropods, mainly ants, have been investigated.", "contents": "[A contribution to the biology of Dicrocoelium hospes Looss, 1907 (Trematoda, Dicrocoeliidae)]. In this study, carried out in the Ivory Coast, Dicrocoelium hospes Looss, 1907 was shown for the first time to be a parasite of cattle and it was also detected in sheep by the presence of ova in the faeces. Up to 50% of the sheep in some flocks were found to shed eggs. The adults, sporocysts, \"slime balls\" and cercariae of D. hospes are described and compared to the respective stages of D. dendriticum. This comparison shows that essential morphological structures are very similar, especially the sensory papillae, which as so called chaetotaxis can serve to distinguish closely related species. The cercariae develop in terrestrial snails of the genus Limicolaria of which several species may play a role (L. flammea, L. felina, L. kambeul). The main habitat of D. hospes seems to be limited to savannah environment; only once could D. hospes be found in the borderzone between savannah and the rain forest. Infected Limicolaria-snails shed the cercariae in amorphous \"slime balls\" of liquid-jelly-like consistency and yellowish colour. Under the influence of sunlight these liquify; the cercariae, however, can survive for up to 26 h. According to our present knowledge the sunlight seems to be a factor which triggers the shedding of slime balls. This begins shortly after sunrise at a temperature of 22 degrees C and a relative humidity of 100%. Infected snails can shed cercariae on seven consecutive days. This kind of slime ball production might provide a clue to the 2nd intermediate host; efforts to identify this host have, however, so far been fruitless, despite the fact that almost 4000 arthropods, mainly ants, have been investigated."}
{"id": "PMID:28657", "title": "Leukokinetic studies in Mediterranean kala azar.", "content": "Two patients with acute Kala Azar were studied with DF32P (diisopropylfluorophosphate) and three patients with 51Cr (chromate) in an attempt to delineate the mechanism producing neutropenia in this disease. The granulocyte life span was found to be reduced in all the patients with exception of one who was studied during Glucantim treatment. The surface radioactivity counts showed that the reduced granulocyte life span was due to pooling and probable destruction of granulocytes in the spleen and to a lesser degree in the liver. Bone marrow neutrophil reserve, evaluated by the response to the intravenous hydrocortisone hemisuccinate, was found to be markedly reduced in all patients. An enlarged marginal granulocyte pool indicated also that the neutropenia may be due to altered intravascular granulocyte distribution.", "contents": "Leukokinetic studies in Mediterranean kala azar. Two patients with acute Kala Azar were studied with DF32P (diisopropylfluorophosphate) and three patients with 51Cr (chromate) in an attempt to delineate the mechanism producing neutropenia in this disease. The granulocyte life span was found to be reduced in all the patients with exception of one who was studied during Glucantim treatment. The surface radioactivity counts showed that the reduced granulocyte life span was due to pooling and probable destruction of granulocytes in the spleen and to a lesser degree in the liver. Bone marrow neutrophil reserve, evaluated by the response to the intravenous hydrocortisone hemisuccinate, was found to be markedly reduced in all patients. An enlarged marginal granulocyte pool indicated also that the neutropenia may be due to altered intravascular granulocyte distribution."}
{"id": "PMID:28661", "title": "Non-invasive assessment of left internal mammary-coronary bypass patency using the external Doppler probe.", "content": "Non-directional blood velocity of left internal mammary bypass grafts was non-invasively studied with the Doppler ultrasonic probe. Thirteen of 14 subjects had angiographic evidence of bypass graft patency and their Doppler signals demonstrated high amplitude phasic blood velocities. A single patient with proximal left internal mammary arterial graft occlusion manifested marked attenuation of Doppler blood velocity signals. It is concluded that this technic offers a potential for ambulatory and in-office screening of internal mammary artery bypass graft function.", "contents": "Non-invasive assessment of left internal mammary-coronary bypass patency using the external Doppler probe. Non-directional blood velocity of left internal mammary bypass grafts was non-invasively studied with the Doppler ultrasonic probe. Thirteen of 14 subjects had angiographic evidence of bypass graft patency and their Doppler signals demonstrated high amplitude phasic blood velocities. A single patient with proximal left internal mammary arterial graft occlusion manifested marked attenuation of Doppler blood velocity signals. It is concluded that this technic offers a potential for ambulatory and in-office screening of internal mammary artery bypass graft function."}
{"id": "PMID:28664", "title": "Carbohydrate metabolism in renal failure.", "content": "Hyperglycemia and impaired glucose tolerance are well known phenomena occurring in patients with renal failure. In contrast to true diabetic subjects, an elevated ratio of insulin to glucose during the glucose tolerance test is consistently observed indicating a peripheral insulin insensitivity. Among the possible reasons, a disturbance at the cellular level seems to be most likely. There is some evidence of reduced peripheral glucose utilization on the one hand and increased hepatic glucose output--probably by stimulation of gluconeogenesis--on the other. Agents that have been suggested to be involved in these alterations of carbohydrate metabolism in uremia are hormones, electrolytes, pH, and \"toxic\" metabolic intermediates or end-products. Of these, an increase in insulin antagonistic hormones; among them growth hormone, catecholamines, and glucagon, seems to be of most significance. Although for the individual hormones no equivocal correlation with glucose intolerance has been proved, the interaction of all of them may result in a preponderance of insulin antagonism thus leading to an apparent insulin resistance.", "contents": "Carbohydrate metabolism in renal failure. Hyperglycemia and impaired glucose tolerance are well known phenomena occurring in patients with renal failure. In contrast to true diabetic subjects, an elevated ratio of insulin to glucose during the glucose tolerance test is consistently observed indicating a peripheral insulin insensitivity. Among the possible reasons, a disturbance at the cellular level seems to be most likely. There is some evidence of reduced peripheral glucose utilization on the one hand and increased hepatic glucose output--probably by stimulation of gluconeogenesis--on the other. Agents that have been suggested to be involved in these alterations of carbohydrate metabolism in uremia are hormones, electrolytes, pH, and \"toxic\" metabolic intermediates or end-products. Of these, an increase in insulin antagonistic hormones; among them growth hormone, catecholamines, and glucagon, seems to be of most significance. Although for the individual hormones no equivocal correlation with glucose intolerance has been proved, the interaction of all of them may result in a preponderance of insulin antagonism thus leading to an apparent insulin resistance."}
{"id": "PMID:28665", "title": "The role of the kidney in the removal of ketone bodies under different acid-base status of the rat.", "content": "Arterial blood concentrations of ketone bodies, pyruvate, lactate, citrate, and oxoglutarate were measured in normal and in nephrectomized rats. The rate of removal from the circulation of an infused acetoacetate load has been studied in both groups of animals. Blood oxoglutarate and ketone bodies remained unchanged in nephrectomized rats. Blood citrate level rose rapidly. In rats with normal blood pH the contribution of the kidneys to the removal of ketone bodies is 28%, whereas in metabolic alkalosis, it is less than 2%. In nephrectomized rats with normal blood pH and in rats with metabolic alkalosis the ratio between beta-hydroxybutyrate and acetoacetate is very high in comparison with rats having metabolic acidosis. These data suggest that in metabolic alkalosis the kidneys are not able to utilize ketone bodies.", "contents": "The role of the kidney in the removal of ketone bodies under different acid-base status of the rat. Arterial blood concentrations of ketone bodies, pyruvate, lactate, citrate, and oxoglutarate were measured in normal and in nephrectomized rats. The rate of removal from the circulation of an infused acetoacetate load has been studied in both groups of animals. Blood oxoglutarate and ketone bodies remained unchanged in nephrectomized rats. Blood citrate level rose rapidly. In rats with normal blood pH the contribution of the kidneys to the removal of ketone bodies is 28%, whereas in metabolic alkalosis, it is less than 2%. In nephrectomized rats with normal blood pH and in rats with metabolic alkalosis the ratio between beta-hydroxybutyrate and acetoacetate is very high in comparison with rats having metabolic acidosis. These data suggest that in metabolic alkalosis the kidneys are not able to utilize ketone bodies."}
{"id": "PMID:28666", "title": "Digestive-absorptive function of the intestinal brush border in uremia.", "content": "Amino acid absorption was studied in chronic uremic rats. Intestinal transport of L-leucine appears to be inhibited with mild uremic intoxication, whereas severe uremia enhances absorption. Brush border activity of intestinal maltase and disaccharidases is higher in rats with chronic renal insufficiency. The same holds for gamma-glutamyl-transpeptidase activity.", "contents": "Digestive-absorptive function of the intestinal brush border in uremia. Amino acid absorption was studied in chronic uremic rats. Intestinal transport of L-leucine appears to be inhibited with mild uremic intoxication, whereas severe uremia enhances absorption. Brush border activity of intestinal maltase and disaccharidases is higher in rats with chronic renal insufficiency. The same holds for gamma-glutamyl-transpeptidase activity."}
{"id": "PMID:28667", "title": "Ulcerative colitis in association with Takayasu's disease.", "content": "A case of total ulcerative colitis associated with large-vessel disease consistent with a diagnosis of Takayasu's disease is described in a 21-year-old Pakistani female. The possible relationship between the two disorders is discussed.", "contents": "Ulcerative colitis in association with Takayasu's disease. A case of total ulcerative colitis associated with large-vessel disease consistent with a diagnosis of Takayasu's disease is described in a 21-year-old Pakistani female. The possible relationship between the two disorders is discussed."}
{"id": "PMID:28670", "title": "Persistent pulmonary hypertension in the neonate: development of an animal model.", "content": "Chronic intrauterine hypoxia was induced in third-trimester lamb fetuses by daily embolization of the maternal side of the placenta with nonradioactive microspheres. After delivery at term, the chronically hypoxic fetuses had significantly increased pulmonary artery pressures when compared to nonhypoxic control measurements. This preparation appears to be a satisfactory model for experimental study of persistent pulmonary hypertension in the neonate.", "contents": "Persistent pulmonary hypertension in the neonate: development of an animal model. Chronic intrauterine hypoxia was induced in third-trimester lamb fetuses by daily embolization of the maternal side of the placenta with nonradioactive microspheres. After delivery at term, the chronically hypoxic fetuses had significantly increased pulmonary artery pressures when compared to nonhypoxic control measurements. This preparation appears to be a satisfactory model for experimental study of persistent pulmonary hypertension in the neonate."}
{"id": "PMID:28671", "title": "Evaluation of continuous monitoring of tissue pH in cats.", "content": "An improved continuous tissue pH monitoring system, designed for human subcutaneous fetal scalp tissue, was evaluated in 10 cats for total of 60 hours. Respiratory acidosis was induced with and without hypoxia to model the pathology of human clinical fetal distress. Arterial and venous pH were sampled every 15 minutes and the values were compared to those from the pH monitor system. The values paralleled arterial and venous blood pH, with correlation coefficients up to 0.98 under various pathologic acidotic conditions.", "contents": "Evaluation of continuous monitoring of tissue pH in cats. An improved continuous tissue pH monitoring system, designed for human subcutaneous fetal scalp tissue, was evaluated in 10 cats for total of 60 hours. Respiratory acidosis was induced with and without hypoxia to model the pathology of human clinical fetal distress. Arterial and venous pH were sampled every 15 minutes and the values were compared to those from the pH monitor system. The values paralleled arterial and venous blood pH, with correlation coefficients up to 0.98 under various pathologic acidotic conditions."}
{"id": "PMID:28672", "title": "Effects of endotoxin on the pregnant baboon and fetus.", "content": "Effects of E. coli endotoxin upon uterine activity and maternal and fetal condition were studied in four pregnant baboons and their fetuses. Uterine activity increased significantly following administration of endotoxin to the mother. Endotoxin also produced maternal circulatory collapse, severe acidosis, and profound fetal asphyxia resulting in death. Death also occurred in three of the four mothers within 24 hours without amelioration of their conditions.", "contents": "Effects of endotoxin on the pregnant baboon and fetus. Effects of E. coli endotoxin upon uterine activity and maternal and fetal condition were studied in four pregnant baboons and their fetuses. Uterine activity increased significantly following administration of endotoxin to the mother. Endotoxin also produced maternal circulatory collapse, severe acidosis, and profound fetal asphyxia resulting in death. Death also occurred in three of the four mothers within 24 hours without amelioration of their conditions."}
{"id": "PMID:28673", "title": "Electron microscopy of nephropathia epidemica. Renal tubular basement membrane.", "content": "Tubular basement membranes in kidney biopsies from 18 patients with nephropathia epidemica were studied by electron microscopy. Both in the cortex and in the medulla there was splitting of the basement membrane. Thickened basement membrane around occasional tubules contained membrane vesicles, usually empty but also with a core and a diameter of approximately 180 nm. Membranous convoluted structures and light finely fibrillar areas in the basement membranes were seen. Splitting of the basement membrane was most prominent in the medulla, and the membrane was filled with round to oval particles 55 to 470 nm in diameter. Of the possible mechanisms of damage at the basement membrane level in this disease, the findings suggest liberation of antigen from the tubular cells and reaction of circulating antibodies with the antigen in the basement membrane.", "contents": "Electron microscopy of nephropathia epidemica. Renal tubular basement membrane. Tubular basement membranes in kidney biopsies from 18 patients with nephropathia epidemica were studied by electron microscopy. Both in the cortex and in the medulla there was splitting of the basement membrane. Thickened basement membrane around occasional tubules contained membrane vesicles, usually empty but also with a core and a diameter of approximately 180 nm. Membranous convoluted structures and light finely fibrillar areas in the basement membranes were seen. Splitting of the basement membrane was most prominent in the medulla, and the membrane was filled with round to oval particles 55 to 470 nm in diameter. Of the possible mechanisms of damage at the basement membrane level in this disease, the findings suggest liberation of antigen from the tubular cells and reaction of circulating antibodies with the antigen in the basement membrane."}
{"id": "PMID:28674", "title": "Demethylation in erythrocytes: a reaction involving hemoglobin.", "content": "A reaction is described in erythrocytes of rat and of man whereby O-methylated metabolites of the catecholamines are demethylated to the corresponding catechols. The reaction was studied by incubating aliquots of erythrocyte lysates with radiolabeled O-methylated compounds and isolating the catechol product by alumina adsorption chromatography. The demethylating activity was located in the cytosol of the erythrocytes. Evidence was strong that oxyhemoglobin was responsible for the reaction: the demethylase activity was inseparable from oxyhemoglobin in several chromatographic separations. In addition, although commercially available hemoglobins were inactive in the reactions, after their conversion to oxyhemoglobin and purification, they did effect demethylation. Methemoglobin did not demethylate guaiacols and in fact inhibited demethylation by oxyhemoglobin. The reaction was inhibited by the addition of reduced pyridine nucleotides and of the methyl acceptor tetrahydrofolic acid.", "contents": "Demethylation in erythrocytes: a reaction involving hemoglobin. A reaction is described in erythrocytes of rat and of man whereby O-methylated metabolites of the catecholamines are demethylated to the corresponding catechols. The reaction was studied by incubating aliquots of erythrocyte lysates with radiolabeled O-methylated compounds and isolating the catechol product by alumina adsorption chromatography. The demethylating activity was located in the cytosol of the erythrocytes. Evidence was strong that oxyhemoglobin was responsible for the reaction: the demethylase activity was inseparable from oxyhemoglobin in several chromatographic separations. In addition, although commercially available hemoglobins were inactive in the reactions, after their conversion to oxyhemoglobin and purification, they did effect demethylation. Methemoglobin did not demethylate guaiacols and in fact inhibited demethylation by oxyhemoglobin. The reaction was inhibited by the addition of reduced pyridine nucleotides and of the methyl acceptor tetrahydrofolic acid."}
{"id": "PMID:28675", "title": "H + transport in urinary epithelia.", "content": "This review of urinary acidification is primarily based on studies in isolated epithelia such as the turtle bladder. Despite the lack of unambiguous proof, the wealth of indirect evidence suggests that the cause of bicarbonate absorption is H+ secretion into the lumen. The mechanisms that regulate H+ transport are discussed. The electrochemical gradient for protons across the membrane is found to be the most fundamental regulator not only of passive movement but also of active transport. CO2 and aldosterone stimulate H+ transport, the latter by a mechanism apparently separate from the effect of this hormone on sodium transport. Although carbonic anhydrase activity is important for optimal function of the H+ pump, the results with carbonic anhydrase inhibitors need to be interpreted with caution. The evidence for Na:H exchange is reviewed and found to be not very persuasive, The metabolic pathways that fuel H+ transport are found to be all the major energy-yielding reactions in the cell, but particular prominence is given to the new discovery of the role of the pentose shunt in energizing transport. Finally, I discuss the important role H+ transport in energy transduction in subcellular organelles.", "contents": "H + transport in urinary epithelia. This review of urinary acidification is primarily based on studies in isolated epithelia such as the turtle bladder. Despite the lack of unambiguous proof, the wealth of indirect evidence suggests that the cause of bicarbonate absorption is H+ secretion into the lumen. The mechanisms that regulate H+ transport are discussed. The electrochemical gradient for protons across the membrane is found to be the most fundamental regulator not only of passive movement but also of active transport. CO2 and aldosterone stimulate H+ transport, the latter by a mechanism apparently separate from the effect of this hormone on sodium transport. Although carbonic anhydrase activity is important for optimal function of the H+ pump, the results with carbonic anhydrase inhibitors need to be interpreted with caution. The evidence for Na:H exchange is reviewed and found to be not very persuasive, The metabolic pathways that fuel H+ transport are found to be all the major energy-yielding reactions in the cell, but particular prominence is given to the new discovery of the role of the pentose shunt in energizing transport. Finally, I discuss the important role H+ transport in energy transduction in subcellular organelles."}
{"id": "PMID:28676", "title": "Hemodynamic functions and blood viscosity in surface hypothermia.", "content": "Hemodynamic functions and blood viscosity changes in hypothermia (core approximately 25 degrees C) were studied in 14 pentobarbital-anesthetized dogs subjected to surface cooling. The viscosity of blood (eta B) increased progressively to 173% of that at 37 degrees C when body temperature was lowered to 25 degrees C. The increase in blood viscosity was caused by: a) the direct effect of low temperature on plasma viscosity, b) hemoconcentration as a result of plasma loss, and c) the low-flow (low-shear) state induced by hypothermia. A larger portion of the increased viscosity was caused by the low-flow state in hypothermia. The systemic flow resistance (SFR) increased to 271% of control, and this was attributable about equally to the increases in blood viscosity and systemic vascular hindrance (SFR/eta B). Similarly, the viscosity of blood contributed significantly to raising the pulmonary flow resistance. The relative constancy of mixed venous O2 saturation suggests that the cardiac output at low body temperature is generally adequate to meet the metabolic needs.", "contents": "Hemodynamic functions and blood viscosity in surface hypothermia. Hemodynamic functions and blood viscosity changes in hypothermia (core approximately 25 degrees C) were studied in 14 pentobarbital-anesthetized dogs subjected to surface cooling. The viscosity of blood (eta B) increased progressively to 173% of that at 37 degrees C when body temperature was lowered to 25 degrees C. The increase in blood viscosity was caused by: a) the direct effect of low temperature on plasma viscosity, b) hemoconcentration as a result of plasma loss, and c) the low-flow (low-shear) state induced by hypothermia. A larger portion of the increased viscosity was caused by the low-flow state in hypothermia. The systemic flow resistance (SFR) increased to 271% of control, and this was attributable about equally to the increases in blood viscosity and systemic vascular hindrance (SFR/eta B). Similarly, the viscosity of blood contributed significantly to raising the pulmonary flow resistance. The relative constancy of mixed venous O2 saturation suggests that the cardiac output at low body temperature is generally adequate to meet the metabolic needs."}
{"id": "PMID:28677", "title": "Field survey of enteric viruses in solid waste landfill leachates.", "content": "Because municipal solid waste may contain fecal material from a variety of sources, there is concern that the leachate discharged from some solid waste landfills may contain enteric pathogens, including enteric viruses. In this study, 22 leachate samples from 21 different landfills in the United States and Canada were examined for enteric viruses. The sites represented a broad range of conditions for solid waste landfills and the leachate samples ranged from 10.3 to 18 liters in volume. Enteric viruses were found in only one of the 22 leachate samples examined. Two viruses, identified as poliovirus types 1 and 3, were found in an 11.8 liter sample obtained from a site where solid waste landfill practice was deficient. The low levels of enteric viruses detected in field samples of raw leachate and the opportunities for further reductions in the virus concentration of leachates by such processes as thermal inactivation, removal by soil and dilution in ground and surface waters, suggest that leachates from properly operated solid waste landfills do not constitute an environmental or public health hazard due to enteric viruses.", "contents": "Field survey of enteric viruses in solid waste landfill leachates. Because municipal solid waste may contain fecal material from a variety of sources, there is concern that the leachate discharged from some solid waste landfills may contain enteric pathogens, including enteric viruses. In this study, 22 leachate samples from 21 different landfills in the United States and Canada were examined for enteric viruses. The sites represented a broad range of conditions for solid waste landfills and the leachate samples ranged from 10.3 to 18 liters in volume. Enteric viruses were found in only one of the 22 leachate samples examined. Two viruses, identified as poliovirus types 1 and 3, were found in an 11.8 liter sample obtained from a site where solid waste landfill practice was deficient. The low levels of enteric viruses detected in field samples of raw leachate and the opportunities for further reductions in the virus concentration of leachates by such processes as thermal inactivation, removal by soil and dilution in ground and surface waters, suggest that leachates from properly operated solid waste landfills do not constitute an environmental or public health hazard due to enteric viruses."}
{"id": "PMID:28678", "title": "The effect of pH on platelet and coagulation factor activities.", "content": "After observing that lavage of the stomach with alkaline solutions has a beneficial effect on the control of gastric hemorrhage, we examined the platelet and coagulation factor activities under conditions of lower and elevated pH. The results showed that change of the pH from acidosis to 7.0 and even to slight alkalosis induces platelet aggregation, platelet calcium and serotonin release, as well as platelet factor II availability. The prothrombin and partial thromboplastin times approached normal levels, whereas the fibrinogen level did not change significantly. The results obtained may serve as an explanation for the control of the intragastric bleeding in patients treated by maintenance of their gastric pH at 7.0.", "contents": "The effect of pH on platelet and coagulation factor activities. After observing that lavage of the stomach with alkaline solutions has a beneficial effect on the control of gastric hemorrhage, we examined the platelet and coagulation factor activities under conditions of lower and elevated pH. The results showed that change of the pH from acidosis to 7.0 and even to slight alkalosis induces platelet aggregation, platelet calcium and serotonin release, as well as platelet factor II availability. The prothrombin and partial thromboplastin times approached normal levels, whereas the fibrinogen level did not change significantly. The results obtained may serve as an explanation for the control of the intragastric bleeding in patients treated by maintenance of their gastric pH at 7.0."}
{"id": "PMID:28682", "title": "Glutathione depletion following inhalation anesthesia.", "content": "Glutathione depletion following inhalation of halogenated anesthetics was investigated as a possible mechanism of toxic reactions associated with anesthesia. Concentrations of reduced glutathione were measured in the blood, liver, lung and kidney of the mouse after anesthesia with enflurane, fluroxene, halothane, isoflurane, methoxyflurane, or trichloroethylene. The anesthetic had no effect on glutathione concentrations in tissues except when fluroxene was used. After two hours of fluroxene anesthesia, glutathione in liver, lung, kidney, and blood was depleted by 93, 85, 85, and 61 per cent, respectively. The depletion was dose-dependent and was more extensive in animals anesthetized after phenobarbital pretreatment. Glutathione was also depleted in livers and lungs of rats anesthetized with fluroxene (60 and 38 per cent, respectively). In blood of rhesus monkeys anesthetized with fluroxene, glutathione was depleted by only 13 per cent. Extents of glutathione depletion are related to fluroxene toxicities in the three species studied.", "contents": "Glutathione depletion following inhalation anesthesia. Glutathione depletion following inhalation of halogenated anesthetics was investigated as a possible mechanism of toxic reactions associated with anesthesia. Concentrations of reduced glutathione were measured in the blood, liver, lung and kidney of the mouse after anesthesia with enflurane, fluroxene, halothane, isoflurane, methoxyflurane, or trichloroethylene. The anesthetic had no effect on glutathione concentrations in tissues except when fluroxene was used. After two hours of fluroxene anesthesia, glutathione in liver, lung, kidney, and blood was depleted by 93, 85, 85, and 61 per cent, respectively. The depletion was dose-dependent and was more extensive in animals anesthetized after phenobarbital pretreatment. Glutathione was also depleted in livers and lungs of rats anesthetized with fluroxene (60 and 38 per cent, respectively). In blood of rhesus monkeys anesthetized with fluroxene, glutathione was depleted by only 13 per cent. Extents of glutathione depletion are related to fluroxene toxicities in the three species studied."}
{"id": "PMID:28683", "title": "Systemic arterial blood pH servocontrol of mechanical ventilation.", "content": "Servocontrol of mechanical ventilation using systemic arterial blood pH, measured by a dual-function pH/PCO2 intra-arterial sensor, as the controlled variable uas carried out in 30 dogs anesthetized with pentobarbital, 30 mg/kg. The control loop consisted of the animal, an intra-arterial dual-function pH/PCO2 sensor and sensor amplifier, a controller, and a Siemans-Elema 900 servoventilator. The system responded appropriately to changes in set-point pH from 7.30 to 7.50, as well as to infusions of lactic acid, which, with the control loop open, decreased systemic arterial blood pH 0.1 TO 0.2 PH units. Long-term (16 hr) ventilation of one dog with the systemic arterial blood pH servocontrol ventilator was shown to be feasible.", "contents": "Systemic arterial blood pH servocontrol of mechanical ventilation. Servocontrol of mechanical ventilation using systemic arterial blood pH, measured by a dual-function pH/PCO2 intra-arterial sensor, as the controlled variable uas carried out in 30 dogs anesthetized with pentobarbital, 30 mg/kg. The control loop consisted of the animal, an intra-arterial dual-function pH/PCO2 sensor and sensor amplifier, a controller, and a Siemans-Elema 900 servoventilator. The system responded appropriately to changes in set-point pH from 7.30 to 7.50, as well as to infusions of lactic acid, which, with the control loop open, decreased systemic arterial blood pH 0.1 TO 0.2 PH units. Long-term (16 hr) ventilation of one dog with the systemic arterial blood pH servocontrol ventilator was shown to be feasible."}
{"id": "PMID:28684", "title": "Inhibition of cutaneous and mucosal allergy with phenyltoloxamine.", "content": "A dose-and-time related-effect of oral phenyltoloxamine citrate, a Class I, H1 antihistamine compound, has been demonstrated against allergen-induced wheal-and-erythema skin reactions among 10 adults with a diagnosis of allergic rhinitis and seasonal pollinosis. Clinical improvement in the existing symptoms of rhinorrhea, nasal obstruction, pruritus and sneezing, showed a significant correlation with the inhibition of reagin-mediated skin reactivity caused by phenytoloxamine. No adverse side effects were observed. It can be concluded that oral phenyltoloxamine citrate possesses antihistaminic properties and a range of safety which make it a useful agent for the symptomatic management of upper respiratory allergy.", "contents": "Inhibition of cutaneous and mucosal allergy with phenyltoloxamine. A dose-and-time related-effect of oral phenyltoloxamine citrate, a Class I, H1 antihistamine compound, has been demonstrated against allergen-induced wheal-and-erythema skin reactions among 10 adults with a diagnosis of allergic rhinitis and seasonal pollinosis. Clinical improvement in the existing symptoms of rhinorrhea, nasal obstruction, pruritus and sneezing, showed a significant correlation with the inhibition of reagin-mediated skin reactivity caused by phenytoloxamine. No adverse side effects were observed. It can be concluded that oral phenyltoloxamine citrate possesses antihistaminic properties and a range of safety which make it a useful agent for the symptomatic management of upper respiratory allergy."}
{"id": "PMID:28686", "title": "Serum medazepam, diazepam, and N-desmethyldiazepam levels after single and multiple oral doses of medazepam.", "content": "20 mg of medazepam were taken by mouth by 9 healthy volunteers in an acute absorption study. About a 10-fold variation was found during the first 6 hours after the drug in individual serum medazepam, diazepam, and N-desmethyldiazepam levels. In a subacute study 10 mg of medazepam t.i.d. was given to 10 institutionalized mentally subnormal adults with emotional disorders. After 14 days' treatment serum N-desmethyldiazepam levels were generally above 800 ng/ml, 7 to 8 times higher than the serum medazepam or diazepam levels measured 12 hours after the last dose. No correlation was observed between the serum concentration and efficacy of medazepam.", "contents": "Serum medazepam, diazepam, and N-desmethyldiazepam levels after single and multiple oral doses of medazepam. 20 mg of medazepam were taken by mouth by 9 healthy volunteers in an acute absorption study. About a 10-fold variation was found during the first 6 hours after the drug in individual serum medazepam, diazepam, and N-desmethyldiazepam levels. In a subacute study 10 mg of medazepam t.i.d. was given to 10 institutionalized mentally subnormal adults with emotional disorders. After 14 days' treatment serum N-desmethyldiazepam levels were generally above 800 ng/ml, 7 to 8 times higher than the serum medazepam or diazepam levels measured 12 hours after the last dose. No correlation was observed between the serum concentration and efficacy of medazepam."}
{"id": "PMID:28687", "title": "Effects of a new beta1-selective beta-blocker H 87/07 in angina pectoris.", "content": "The efficacy and toleration of a new beta1-selective beta-blocker, H 87/07, was compared with placebo in 33 patients with angina pectoris. The efficacy was evaluated using subjective assessments of attack rate and nitroglycerin consumption as well as objective assessments of exercise tolerance on a bicycle ergometer. H 87/07 significantly reduced the attack rate and the nitroglycerin consumption compared with placebo. The mean reduction amounted to 13 and 36% respectively. No significant differences were found between H 87/07 and placebo with regard to exercise tolerance. Due to high intrinsic stimulating activity (I.S.A.) H 87/07 altered the heart rate and blood pressure only slightly at rest but during exercise significant reductions were seen. Except for one patient who had cardiac decompensation on H 87/07 no side-effects of clinical importance were seen. No significant changes were seen with regard to the laboratory tests performed.", "contents": "Effects of a new beta1-selective beta-blocker H 87/07 in angina pectoris. The efficacy and toleration of a new beta1-selective beta-blocker, H 87/07, was compared with placebo in 33 patients with angina pectoris. The efficacy was evaluated using subjective assessments of attack rate and nitroglycerin consumption as well as objective assessments of exercise tolerance on a bicycle ergometer. H 87/07 significantly reduced the attack rate and the nitroglycerin consumption compared with placebo. The mean reduction amounted to 13 and 36% respectively. No significant differences were found between H 87/07 and placebo with regard to exercise tolerance. Due to high intrinsic stimulating activity (I.S.A.) H 87/07 altered the heart rate and blood pressure only slightly at rest but during exercise significant reductions were seen. Except for one patient who had cardiac decompensation on H 87/07 no side-effects of clinical importance were seen. No significant changes were seen with regard to the laboratory tests performed."}
{"id": "PMID:28690", "title": "Chloramphenicol acetyltransferase of Bacteroides fragilis.", "content": "Chloramphenicol-resistant strains of Bacteroides fragilis (minimum inhibitory concentration, 12.5 mug/ml) were isolated from a stool specimen which contained multiply resistant Escherichia coli. The enzyme responsible for resistance, chloramphenicol acetyltransferase, was produced constitutively by these strains; the specific activity was 10-fold lower than that of the E. coli enzymes. Similar activity was not detected in susceptible B. fragilis strains, nor could it be induced by growth in the presence of chloramphenicol or by mutagenesis. The enzyme had a pH optimum of 7.8 and a molecular weight of approximately 89,000. The K(m) for chloramphenicol was 5.2 muM, and the enzyme was sensitive to inhibition by 5,5'-dithiobis-2-nitrobenzoic acid. The enzyme produced by an E. coli strain isolated from the same specimen had a similar K(m) and sensitivity to 5,5'-dithiobis-2-nitrobenzoic acid.", "contents": "Chloramphenicol acetyltransferase of Bacteroides fragilis. Chloramphenicol-resistant strains of Bacteroides fragilis (minimum inhibitory concentration, 12.5 mug/ml) were isolated from a stool specimen which contained multiply resistant Escherichia coli. The enzyme responsible for resistance, chloramphenicol acetyltransferase, was produced constitutively by these strains; the specific activity was 10-fold lower than that of the E. coli enzymes. Similar activity was not detected in susceptible B. fragilis strains, nor could it be induced by growth in the presence of chloramphenicol or by mutagenesis. The enzyme had a pH optimum of 7.8 and a molecular weight of approximately 89,000. The K(m) for chloramphenicol was 5.2 muM, and the enzyme was sensitive to inhibition by 5,5'-dithiobis-2-nitrobenzoic acid. The enzyme produced by an E. coli strain isolated from the same specimen had a similar K(m) and sensitivity to 5,5'-dithiobis-2-nitrobenzoic acid."}
{"id": "PMID:28691", "title": "Biological effects of 5-carboxy-2'-deoxyuridine: hydrolysis product of 5-trifluoromethyl-2'-deoxyuridine.", "content": "5-Carboxy-2'-deoxyuridine (5-COOH-2'-dUrd) is a product of the base-catalyzed hydrolysis of 5-trifluoromethyl-2'-deoxyuridine. Hydrolysis of 5-trifluoromethyl-2'-deoxyuridine to 5-COOH-2'-dUrd in phosphate-buffered saline was kinetically first order and was pH dependent. At 37 degrees C and pH 7.0, 7.5, and 8.0, hydrolysis occurred with rate constants of 4.19 x 10(-5), 9.30 x 10(-5), and 1.61 x 10(-4) s(-1), respectively, with corresponding half-lives of 45.7, 20.6, and 11.9 h. 5-COOH-2'-dUrd inhibited growth of HEp-2 cells by 21, 67, and 91% at 1.0, 10, and 100 muM, with no antiviral activity against herpes simplex virus type 1 or herpes simplex virus type 2 at 1.0 or 10 muM. Partial reversal of cytotoxicity in HEp-2 cells was achieved with orotidine, uridine, deoxythymidine, or deoxycytidine, whereas complete reversal of cytotoxic effects was achieved with simultaneous addition of deoxythymidine, deoxycytidine, and uridine. 5-COOH-2'-dUrd at 50 muM inhibited incorporation of [(14)C]orotate into RNA and DNA by 65 and 27%, respectively. 5-COOH-2'-dUrd had no effect on the incorporation of [(3)H]uridine into DNA or RNA. Because of the structural similarities to deoxythymidine, 5-COOH-2'-dUrd was tested as an inhibitor of deoxythymidine kinase. 5-COOH-2'-dUrd was neither a substrate nor an inhibitor of herpes simplex virus type 1 induced deoxythymidine kinase or HEp-2 cell deoxythymidine kinase. Based on these observations, the metabolic block induced by 5-COOH-2'-dUrd has been localized to the de novo pyrimidine biosynthetic pathway between orotate phosphoribosyl transferase and orotidine 5'-phosphate decarboxylase.", "contents": "Biological effects of 5-carboxy-2'-deoxyuridine: hydrolysis product of 5-trifluoromethyl-2'-deoxyuridine. 5-Carboxy-2'-deoxyuridine (5-COOH-2'-dUrd) is a product of the base-catalyzed hydrolysis of 5-trifluoromethyl-2'-deoxyuridine. Hydrolysis of 5-trifluoromethyl-2'-deoxyuridine to 5-COOH-2'-dUrd in phosphate-buffered saline was kinetically first order and was pH dependent. At 37 degrees C and pH 7.0, 7.5, and 8.0, hydrolysis occurred with rate constants of 4.19 x 10(-5), 9.30 x 10(-5), and 1.61 x 10(-4) s(-1), respectively, with corresponding half-lives of 45.7, 20.6, and 11.9 h. 5-COOH-2'-dUrd inhibited growth of HEp-2 cells by 21, 67, and 91% at 1.0, 10, and 100 muM, with no antiviral activity against herpes simplex virus type 1 or herpes simplex virus type 2 at 1.0 or 10 muM. Partial reversal of cytotoxicity in HEp-2 cells was achieved with orotidine, uridine, deoxythymidine, or deoxycytidine, whereas complete reversal of cytotoxic effects was achieved with simultaneous addition of deoxythymidine, deoxycytidine, and uridine. 5-COOH-2'-dUrd at 50 muM inhibited incorporation of [(14)C]orotate into RNA and DNA by 65 and 27%, respectively. 5-COOH-2'-dUrd had no effect on the incorporation of [(3)H]uridine into DNA or RNA. Because of the structural similarities to deoxythymidine, 5-COOH-2'-dUrd was tested as an inhibitor of deoxythymidine kinase. 5-COOH-2'-dUrd was neither a substrate nor an inhibitor of herpes simplex virus type 1 induced deoxythymidine kinase or HEp-2 cell deoxythymidine kinase. Based on these observations, the metabolic block induced by 5-COOH-2'-dUrd has been localized to the de novo pyrimidine biosynthetic pathway between orotate phosphoribosyl transferase and orotidine 5'-phosphate decarboxylase."}
{"id": "PMID:28692", "title": "Streptococcin A-FF22: nisin-like antibiotic substance produced by a group A streptococcus.", "content": "Streptococcin A-FF22 (SA) was shown to occur as both a cell-associated (SA-CA) and an extracellular (SA-EX) component of cultures of the producer bacterium, group A streptococcus strain FF22. SA-CA was solubilized by chemical, enzymatic, and mechanical procedures, similar to those used to release M protein. The independence of SA and M protein in strain FF22 was established by chromatographic separation of the two proteins on the basis of molecular weight and isoelectric point differences between the two substances. Media supporting optimal growth of strain FF22 did not necessarily favor SA production. SA was not produced either at elevated temperatures (39 degrees C) or if the culture was maintained at pH 7 or higher. The release of SA from producer cells was enhanced at lower culture pH values. Much of the SA-CA activity seemed associated with the cell walls of the producer strain, and the nature of the binding appeared to be largely nonspecific in nature and attributable to electrostatic interaction.", "contents": "Streptococcin A-FF22: nisin-like antibiotic substance produced by a group A streptococcus. Streptococcin A-FF22 (SA) was shown to occur as both a cell-associated (SA-CA) and an extracellular (SA-EX) component of cultures of the producer bacterium, group A streptococcus strain FF22. SA-CA was solubilized by chemical, enzymatic, and mechanical procedures, similar to those used to release M protein. The independence of SA and M protein in strain FF22 was established by chromatographic separation of the two proteins on the basis of molecular weight and isoelectric point differences between the two substances. Media supporting optimal growth of strain FF22 did not necessarily favor SA production. SA was not produced either at elevated temperatures (39 degrees C) or if the culture was maintained at pH 7 or higher. The release of SA from producer cells was enhanced at lower culture pH values. Much of the SA-CA activity seemed associated with the cell walls of the producer strain, and the nature of the binding appeared to be largely nonspecific in nature and attributable to electrostatic interaction."}
{"id": "PMID:28693", "title": "Mechanism of the antimicrobial action of pyrithione: effects on membrane transport, ATP levels, and protein synthesis.", "content": "Pyrithione is a general inhibitor of membrane transport processes in fungi. A brief preincubation of Penicillium mycelia with pyrithione resulted in a marked decrease in the activities of a variety of independently regulated transport systems, including those for inorganic sulfate, inorganic phosphate, methylamine (actually, the NH(4) (+) permease), choline-O-sulfate, glucose, l-methionine (a specific system), and several hydrophobic l-alpha-amino acids (the general amino acid permease). The degree of inhibition at any fixed pyrithione concentration and exposure time increased as the pH of the incubation medium was decreased. This result strongly suggests that the active species is the un-ionized molecule and that pyrithione acts by collapsing a transmembrane DeltapH driving force. The degree of transport inhibition caused by a given concentration of pyrithione increased with increasing time of exposure to the inhibitor. However, exposure time and pyrithione concentration were not reciprocally related. At \"low\" pyrithione concentrations, transport inhibition plateaued at some finite value. This observation suggests that the fungi can detoxify low levels of the inhibitor. The concentration of pyrithione required for a given degree of growth inhibition increased as the experimental mycelial density increased. This phenomenon was consistent with the suggestion that the fungi are capable of inactivating pyrithione.", "contents": "Mechanism of the antimicrobial action of pyrithione: effects on membrane transport, ATP levels, and protein synthesis. Pyrithione is a general inhibitor of membrane transport processes in fungi. A brief preincubation of Penicillium mycelia with pyrithione resulted in a marked decrease in the activities of a variety of independently regulated transport systems, including those for inorganic sulfate, inorganic phosphate, methylamine (actually, the NH(4) (+) permease), choline-O-sulfate, glucose, l-methionine (a specific system), and several hydrophobic l-alpha-amino acids (the general amino acid permease). The degree of inhibition at any fixed pyrithione concentration and exposure time increased as the pH of the incubation medium was decreased. This result strongly suggests that the active species is the un-ionized molecule and that pyrithione acts by collapsing a transmembrane DeltapH driving force. The degree of transport inhibition caused by a given concentration of pyrithione increased with increasing time of exposure to the inhibitor. However, exposure time and pyrithione concentration were not reciprocally related. At \"low\" pyrithione concentrations, transport inhibition plateaued at some finite value. This observation suggests that the fungi can detoxify low levels of the inhibitor. The concentration of pyrithione required for a given degree of growth inhibition increased as the experimental mycelial density increased. This phenomenon was consistent with the suggestion that the fungi are capable of inactivating pyrithione."}
{"id": "PMID:28694", "title": "Piperacillin: in vitro evaluation.", "content": "The in vitro activity of a new semisynthetic penicillin, piperacillin, was determined against 577 clinical isolates of gram-positive cocci and gram-negative bacilli. A concentration of 12.5 mug/ml inhibited 92% of isolates of Pseudomonas aeruginosa, 82% of Serratia marcescens, 73% of Escherichia coli, 61% of Klebsiella spp., and 42% of Enterobacter spp. Most Proteus spp. were extremely susceptible; over 85% were inhibited by 0.10 mug/ml. Piperacillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. The type of media and pH had variable effects on the activity of piperacillin, depending upon the organism. Piperacillin was generally less active than PC-904 against gram-negative bacilli, but was consistently more active than carbenicillin and ticarcillin.", "contents": "Piperacillin: in vitro evaluation. The in vitro activity of a new semisynthetic penicillin, piperacillin, was determined against 577 clinical isolates of gram-positive cocci and gram-negative bacilli. A concentration of 12.5 mug/ml inhibited 92% of isolates of Pseudomonas aeruginosa, 82% of Serratia marcescens, 73% of Escherichia coli, 61% of Klebsiella spp., and 42% of Enterobacter spp. Most Proteus spp. were extremely susceptible; over 85% were inhibited by 0.10 mug/ml. Piperacillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. The type of media and pH had variable effects on the activity of piperacillin, depending upon the organism. Piperacillin was generally less active than PC-904 against gram-negative bacilli, but was consistently more active than carbenicillin and ticarcillin."}
{"id": "PMID:28695", "title": "Danger of bucolome in infants with hyperbilirubinaemia. Experimental evidence.", "content": "Effects of bucolome on congenitally jaundiced Gunn rats were examined. Plasma total bilirubin level fell immediately after a single injection of bucolome and the lowered level persisted for more than 6 hours. Plasma unbound-bilirubin level and cerebellar bilirubin content increased simultaneously with the drop in total plasma bilirubin level. Kernicterus was observed in the brains of the treated rats 6 hours after the treatment. LD50 of the drug in jaundiced rats was about 37 mg/kg, about one-tenth of the value in nonjaundiced rats. It is suggested that bucolome displaces bilirubin from albumin, transferring bilirubin from blood into tissues including the brain, and resulting in kernicterus. The use of bucolome in infants with hyperbilirubinaemia is inadvisable.", "contents": "Danger of bucolome in infants with hyperbilirubinaemia. Experimental evidence. Effects of bucolome on congenitally jaundiced Gunn rats were examined. Plasma total bilirubin level fell immediately after a single injection of bucolome and the lowered level persisted for more than 6 hours. Plasma unbound-bilirubin level and cerebellar bilirubin content increased simultaneously with the drop in total plasma bilirubin level. Kernicterus was observed in the brains of the treated rats 6 hours after the treatment. LD50 of the drug in jaundiced rats was about 37 mg/kg, about one-tenth of the value in nonjaundiced rats. It is suggested that bucolome displaces bilirubin from albumin, transferring bilirubin from blood into tissues including the brain, and resulting in kernicterus. The use of bucolome in infants with hyperbilirubinaemia is inadvisable."}
{"id": "PMID:28696", "title": "[gamma-Glutamyl transpeptidase in human eccrine sweat (author's transl)].", "content": "The concentration of gamma-glutamyl transpeptidase was determined in eccrine, thermal sweat of 56 healthy men (ages 20--60 years) and 48 healthy women (ages 17--55 years). Samples of sweat were collected from the chest and back. The concentrations of gamma-glutamyl transpeptidase showed great individual variations. The sex specific comparison of the concentrations of gamma-glutamyl transpeptidase revealed that the women excreted in the sweat from the chest and the back nearly the double amount of this enzyme. The gamma-glutamyl transpeptidase concentrations determined in the sweat from the chest of the examined men and women were three times higher as compared with those excreted simultaneous from the back of the same persons. In the group of the women was this differences statistically significant.", "contents": "[gamma-Glutamyl transpeptidase in human eccrine sweat (author's transl)]. The concentration of gamma-glutamyl transpeptidase was determined in eccrine, thermal sweat of 56 healthy men (ages 20--60 years) and 48 healthy women (ages 17--55 years). Samples of sweat were collected from the chest and back. The concentrations of gamma-glutamyl transpeptidase showed great individual variations. The sex specific comparison of the concentrations of gamma-glutamyl transpeptidase revealed that the women excreted in the sweat from the chest and the back nearly the double amount of this enzyme. The gamma-glutamyl transpeptidase concentrations determined in the sweat from the chest of the examined men and women were three times higher as compared with those excreted simultaneous from the back of the same persons. In the group of the women was this differences statistically significant."}
{"id": "PMID:28698", "title": "Surgery for short esophagus with stricture: an experimental and clinical manometric study.", "content": "The surgical management of short esophagus with stricture has been simplified in recent years by the introduction of an esophageal lengthening procedure (Collis gastroplasty) combined with antireflux maneuvers, such as the Belsey and Nissen operations. This report compares the experimental and clinical manometric findings after these procedures. After myectomy of the lower esophageal sphincter (LES) in the cat, three experimental groups were developed including Collis gastroplasty, Collis-Belsey and Collis-Nissen. formation of a gastric tube did not provide protection against reflux while the Collis-Nissen procedure was more effective than the Collis-Belsey in raising pressures at the high pressure zone (HPZ) (26.0 +/- 3.5 cm H2O vs 15.0 +/- 2.7) and in preventing reflux (pH 6.3 +/- 0.5 vs 2.9 +/- 0.04). Of 20 patients with short esophagus and stricture, 11 underwent a Collis-Belsey procedure and nine a Collis-Nissen procedure. The latter procedure resulted in an HPZ of greater amplitude and length than the Collis-Belsey (18.7 +/- 2.3 mm Hg vs 11.6 +/- 1.7 and 3.9 +/- 0.4 cm vs 2.4 +/- 0.2). It also proved to be a more effective antireflux procedure, for no patient so treated had a positive pH reflux test after operation whereas after the Collis-Belsey procedure all but one patient had a positive pH reflux test. Short-term clinical results also support the superiority of the Collis-Nissen operation.", "contents": "Surgery for short esophagus with stricture: an experimental and clinical manometric study. The surgical management of short esophagus with stricture has been simplified in recent years by the introduction of an esophageal lengthening procedure (Collis gastroplasty) combined with antireflux maneuvers, such as the Belsey and Nissen operations. This report compares the experimental and clinical manometric findings after these procedures. After myectomy of the lower esophageal sphincter (LES) in the cat, three experimental groups were developed including Collis gastroplasty, Collis-Belsey and Collis-Nissen. formation of a gastric tube did not provide protection against reflux while the Collis-Nissen procedure was more effective than the Collis-Belsey in raising pressures at the high pressure zone (HPZ) (26.0 +/- 3.5 cm H2O vs 15.0 +/- 2.7) and in preventing reflux (pH 6.3 +/- 0.5 vs 2.9 +/- 0.04). Of 20 patients with short esophagus and stricture, 11 underwent a Collis-Belsey procedure and nine a Collis-Nissen procedure. The latter procedure resulted in an HPZ of greater amplitude and length than the Collis-Belsey (18.7 +/- 2.3 mm Hg vs 11.6 +/- 1.7 and 3.9 +/- 0.4 cm vs 2.4 +/- 0.2). It also proved to be a more effective antireflux procedure, for no patient so treated had a positive pH reflux test after operation whereas after the Collis-Belsey procedure all but one patient had a positive pH reflux test. Short-term clinical results also support the superiority of the Collis-Nissen operation."}
{"id": "PMID:28699", "title": "The neuropharmacological actions of amoxapine.", "content": "Amoxapine possesses a broad spectrum of psychotropic actions, including antidepressant and neuroleptic effects in animals. Antidepressant activity is characterized by its ability to inhibit tetrabenazine-induced depression, antagonize reserpine-induced hypothermia and enhance yohimbine lethality. Neuroleptic activity is demonstrated by the ability of amoxapine to decrease locomotor activity, induce ptosis and catalepsy, inhibit apomorphine gnawing and amphetamine stereotyped behavior and by characteristic changes in monkey discriminated avoidance behavior. The fact that punished responding in squirrel monkeys was present was present after repeated administration may indicate an anti-anxiety action of this drug. Evidence is offered that the conversion of the tertiary terminal nitrogen to a secondary amine may alter the pharmacologica properties of dibenzoxazepines in a similar way to the for the phenothiazines.", "contents": "The neuropharmacological actions of amoxapine. Amoxapine possesses a broad spectrum of psychotropic actions, including antidepressant and neuroleptic effects in animals. Antidepressant activity is characterized by its ability to inhibit tetrabenazine-induced depression, antagonize reserpine-induced hypothermia and enhance yohimbine lethality. Neuroleptic activity is demonstrated by the ability of amoxapine to decrease locomotor activity, induce ptosis and catalepsy, inhibit apomorphine gnawing and amphetamine stereotyped behavior and by characteristic changes in monkey discriminated avoidance behavior. The fact that punished responding in squirrel monkeys was present was present after repeated administration may indicate an anti-anxiety action of this drug. Evidence is offered that the conversion of the tertiary terminal nitrogen to a secondary amine may alter the pharmacologica properties of dibenzoxazepines in a similar way to the for the phenothiazines."}
{"id": "PMID:28700", "title": "Deoxycytidine: a morphine antagonist.", "content": "Deoxycytidine antagonizes the analgesic action of morphine in the rat, morphine-induced respiratory depression in the rabbit and mitigates withdrawal in the dependent mouse. Administration of deoxycytidine does not precipitate the abstinence syndrome in dependent mice, a property shared by certain other endogenous morphine antagonsits. Cytidine and thymidine closely related in structure to deoxycytidine, are interchangeable with saline as controls, indicating a high degree of specificity in the receptor involved in the \"action-effects\" sequence. The requirement for deoxycytidine in countering the effects of morphine parallels the requirement for certain other DNA pyrimidines in the antagonism of barbiturate and alcohol. The rapidity of antogonist action suggests that such a DNA species would presumably be localized in the synaptosome, at outer membrane or the synaptic junction.", "contents": "Deoxycytidine: a morphine antagonist. Deoxycytidine antagonizes the analgesic action of morphine in the rat, morphine-induced respiratory depression in the rabbit and mitigates withdrawal in the dependent mouse. Administration of deoxycytidine does not precipitate the abstinence syndrome in dependent mice, a property shared by certain other endogenous morphine antagonsits. Cytidine and thymidine closely related in structure to deoxycytidine, are interchangeable with saline as controls, indicating a high degree of specificity in the receptor involved in the \"action-effects\" sequence. The requirement for deoxycytidine in countering the effects of morphine parallels the requirement for certain other DNA pyrimidines in the antagonism of barbiturate and alcohol. The rapidity of antogonist action suggests that such a DNA species would presumably be localized in the synaptosome, at outer membrane or the synaptic junction."}
{"id": "PMID:28701", "title": "The effect of chronic administration of digitoxin on the activity of the myocardial (Na + K)-ATPase in guinea-pigs.", "content": "When guinea-pigs were treated for 24 days with digitoxin 0.3 mg/kg s.c., the activity of the (Na + K)-ATPase of the heart muscle increased by about 30% compared to controls, whereas the enzymes prepared from kidney and brain showed no significant alteration in their activity. In animal species treated with digitoxin for 1 to 5 days, no increase of enzyme activity was observed. Only after 10 to 15 days of treatment, a significant increase of the (Na + K)-ATPase activity was noted which increased no further with treatment up to 24 days. There was no significant difference in the kinetic properties of the (Na + K)-ATPase prepared from digitoxin-treated animals compared to those from control animals; the KM-values for ATP remained unchanged, and there was the same dependence of the activity on the K+-concentration and the same sensitivity towards digitoxin. As there appears to be no significant change in the specific properties of the enzyme, the increase in activity may possibly be caused by an increase in the amount of enzyme as a result of an adaptive enzyme regulation.", "contents": "The effect of chronic administration of digitoxin on the activity of the myocardial (Na + K)-ATPase in guinea-pigs. When guinea-pigs were treated for 24 days with digitoxin 0.3 mg/kg s.c., the activity of the (Na + K)-ATPase of the heart muscle increased by about 30% compared to controls, whereas the enzymes prepared from kidney and brain showed no significant alteration in their activity. In animal species treated with digitoxin for 1 to 5 days, no increase of enzyme activity was observed. Only after 10 to 15 days of treatment, a significant increase of the (Na + K)-ATPase activity was noted which increased no further with treatment up to 24 days. There was no significant difference in the kinetic properties of the (Na + K)-ATPase prepared from digitoxin-treated animals compared to those from control animals; the KM-values for ATP remained unchanged, and there was the same dependence of the activity on the K+-concentration and the same sensitivity towards digitoxin. As there appears to be no significant change in the specific properties of the enzyme, the increase in activity may possibly be caused by an increase in the amount of enzyme as a result of an adaptive enzyme regulation."}
{"id": "PMID:28697", "title": "[Research of the soluble microbial substances in organic fluids for the rapid diagnosis of some infections and particularly of bacterial meningitis (author's transl)].", "content": "A number of immunological and non-immunological techniques have been recently used to detect soluble microbial substances in body fluids of patients with acute meningitis, bacteremia, and lobar pneumonia. By the immunological methods capsular highly polymerized polisaccharide group- or type-specific antigens of the most common C. N. S. pathogens (N. meningitidis A, B, and C; Str. pneumoniae, H. influenzae type b, E. coli K1, mucoid Pseudomonas, Cryptococcus neoformans) can be detected and quantitated in spinal fluids, sera, urine and other fluids specimens from meningitic patients. Capsular type-specific antigens from pneumococcus, and likely from H. influenzae as well, can be detected in sputum from patients with lower respiratory infection. Among the various techniques, the radioimmunoassay appears as the most sensitive one, but high diagnostic sensitivity can be also achieved by using the latex agglutination, haemoagglutination inhibition and coagglutination tests. Counterimmunoelectrophoresis, however, is still the far most used technique for determining soluble microbial antigens, albeit its sensitivity is significantly less than the one of the above mentioned methods. High specificity and some advantages in serotyping the causal organisms are probably the main reasons of such preferential employment. Among the non-immunological techniques the evaluation of lactate and lactic dehydrogenase has been used by some Author for differentiating between bacterial and non bacterial meningitis, and the limulus test for detecting Gram-negative bacterial endotoxins with a high degree of sensitivity and specificity. Finally, the liquid gas chromatography has been evaluated in detection of some organic products (microbial?), such as acids, amines, neutral compounds, in spinal fluid, allowing the differential diagnosis between bacterial, tuberculous, viral, and cryptococcal meningitis. In the present review sensitivity, specificity, and other properties of each test alone and in comparison with the conventional microbiological methods (Gram and culture) are evaluated and the biological and pathogenic role and significance of the soluble microbial antigens and endotoxin are discussed.", "contents": "[Research of the soluble microbial substances in organic fluids for the rapid diagnosis of some infections and particularly of bacterial meningitis (author's transl)]. A number of immunological and non-immunological techniques have been recently used to detect soluble microbial substances in body fluids of patients with acute meningitis, bacteremia, and lobar pneumonia. By the immunological methods capsular highly polymerized polisaccharide group- or type-specific antigens of the most common C. N. S. pathogens (N. meningitidis A, B, and C; Str. pneumoniae, H. influenzae type b, E. coli K1, mucoid Pseudomonas, Cryptococcus neoformans) can be detected and quantitated in spinal fluids, sera, urine and other fluids specimens from meningitic patients. Capsular type-specific antigens from pneumococcus, and likely from H. influenzae as well, can be detected in sputum from patients with lower respiratory infection. Among the various techniques, the radioimmunoassay appears as the most sensitive one, but high diagnostic sensitivity can be also achieved by using the latex agglutination, haemoagglutination inhibition and coagglutination tests. Counterimmunoelectrophoresis, however, is still the far most used technique for determining soluble microbial antigens, albeit its sensitivity is significantly less than the one of the above mentioned methods. High specificity and some advantages in serotyping the causal organisms are probably the main reasons of such preferential employment. Among the non-immunological techniques the evaluation of lactate and lactic dehydrogenase has been used by some Author for differentiating between bacterial and non bacterial meningitis, and the limulus test for detecting Gram-negative bacterial endotoxins with a high degree of sensitivity and specificity. Finally, the liquid gas chromatography has been evaluated in detection of some organic products (microbial?), such as acids, amines, neutral compounds, in spinal fluid, allowing the differential diagnosis between bacterial, tuberculous, viral, and cryptococcal meningitis. In the present review sensitivity, specificity, and other properties of each test alone and in comparison with the conventional microbiological methods (Gram and culture) are evaluated and the biological and pathogenic role and significance of the soluble microbial antigens and endotoxin are discussed."}
{"id": "PMID:28702", "title": "A study of the mechanism of transport of benzylpenicillin in the rat submaxillary gland.", "content": "In vitro studies performed on slices of rat submaxillary gland to evaluate uptake and efflux of 14C-benzylpenicillin (10(-6)M, 10(-5)M) showed that uptake of 14C-benzylpenicillin was not significantly altered by aeration with N2, addition of 10(-5)M CN- or 10(-3) M probenecid, or substitution of K2SO4 in place of NaCl in the KRT buffer to produce a depolarizing solution. Lowering the extracellular pH (pHe) resulted in increases rates of uptake and efflux, whereas increasing the pHe resulted in decreased rates. The in vivo uptake of penicillin into whole glands excised from rates treated in vivo was very similar to that seen in the slice preparation. However, addition of probenecid to salivary gland slices in vitro decreased the rate of effux. These data suggest that the movement of penicillin in the rat salivary gland may occur by a two-step mechanism: (1) passive exchange of penicillin into the gland dependent on the degree of dissociation of penicillin, and (2) active excretion of the drug from the gland by a transport mechanism similar to that of the kidney densitive to probenecid.", "contents": "A study of the mechanism of transport of benzylpenicillin in the rat submaxillary gland. In vitro studies performed on slices of rat submaxillary gland to evaluate uptake and efflux of 14C-benzylpenicillin (10(-6)M, 10(-5)M) showed that uptake of 14C-benzylpenicillin was not significantly altered by aeration with N2, addition of 10(-5)M CN- or 10(-3) M probenecid, or substitution of K2SO4 in place of NaCl in the KRT buffer to produce a depolarizing solution. Lowering the extracellular pH (pHe) resulted in increases rates of uptake and efflux, whereas increasing the pHe resulted in decreased rates. The in vivo uptake of penicillin into whole glands excised from rates treated in vivo was very similar to that seen in the slice preparation. However, addition of probenecid to salivary gland slices in vitro decreased the rate of effux. These data suggest that the movement of penicillin in the rat salivary gland may occur by a two-step mechanism: (1) passive exchange of penicillin into the gland dependent on the degree of dissociation of penicillin, and (2) active excretion of the drug from the gland by a transport mechanism similar to that of the kidney densitive to probenecid."}
{"id": "PMID:28703", "title": "Adrenergic contribution to the motor transmission in the dog vas deferens.", "content": "Isolated vas deferens preparations from 9 dogs were subjected to electrical stimulation and chemical excitation under physiological conditions. The experimental smooth muscle cylinders were confined to the terminal 3 cm portions of either the distal 'urethral' segment or the proximal 'epididymal' segment. Intermittent field stimulation, at 60 sec intervals, was provided by a stimulator of low output impedance under constant parameters of frequency and voltage and an occasionally varied pulse width. Results from this examination completely confirmed the following: (i) a high degree of contractile sensitivity to minute doses of noradrenaline (0.03--0.03 micron; 10(-8)-10(-7) g/ml) and tyramine 0.58 micron (10(-7) g/ml; (ii) an apparent ease and rapidity of extinguishing the electrically-induced twitches by either small doses of phentolamine 0.25 micron (10(-7) g/ml) or phenoxybenzamine 5.8 micron (2 x 10(-6) g/ml); (iii) a complete absence of any inhibitory action by tyramine or noradrenaline on the electrically-induced twitches. The behavior of this motor transmission of the longitudinal muscle of the vas deferens to classical alpha-adrenoceptor blocking agents and the intense susceptibility to the motor actions of the putative neurotransmitter clearly fit in with a picture of an adrenergic implication in this mode of transmission.", "contents": "Adrenergic contribution to the motor transmission in the dog vas deferens. Isolated vas deferens preparations from 9 dogs were subjected to electrical stimulation and chemical excitation under physiological conditions. The experimental smooth muscle cylinders were confined to the terminal 3 cm portions of either the distal 'urethral' segment or the proximal 'epididymal' segment. Intermittent field stimulation, at 60 sec intervals, was provided by a stimulator of low output impedance under constant parameters of frequency and voltage and an occasionally varied pulse width. Results from this examination completely confirmed the following: (i) a high degree of contractile sensitivity to minute doses of noradrenaline (0.03--0.03 micron; 10(-8)-10(-7) g/ml) and tyramine 0.58 micron (10(-7) g/ml; (ii) an apparent ease and rapidity of extinguishing the electrically-induced twitches by either small doses of phentolamine 0.25 micron (10(-7) g/ml) or phenoxybenzamine 5.8 micron (2 x 10(-6) g/ml); (iii) a complete absence of any inhibitory action by tyramine or noradrenaline on the electrically-induced twitches. The behavior of this motor transmission of the longitudinal muscle of the vas deferens to classical alpha-adrenoceptor blocking agents and the intense susceptibility to the motor actions of the putative neurotransmitter clearly fit in with a picture of an adrenergic implication in this mode of transmission."}
{"id": "PMID:28704", "title": "In vitro measurement of the beta-adrenergic blocking properties of ORF 12592, the 5-hydroxy analog of propranolol.", "content": "ORF 12592 caused concentration-dependent inhibition of isoproterenol stimulated adenylate cyclase activity in sarcolemma-enriched membrane preparations of guinea-pig myocardium. Its potency was slightly less than that of d,l-propranolol. ORF 12592 did not stimulate basal enzyme activity, suggesting it to be devoid of intrinsic sympathomimetic activity. It produced no marked inhibition of basal activity, nor did it inhibit sodium fluoride stimulated enzyme activity, indicating that the compound acts at the receptor rather than the catalytic site of the beta-adrenergic receptor-adenylate cyclase complex. ORF 12592 competed for binding of 3H-dihydroalprenolol to specific beta1 and beta2-adrenergic binding sites on turkey and leopard frog erythrocyte membranes respectively. Concentration-binding inhibition curves indicated that ORF 12592 is a non-selective beta-blocker with slightly less affinity for each beta-adrenergic receptor than propranolol.", "contents": "In vitro measurement of the beta-adrenergic blocking properties of ORF 12592, the 5-hydroxy analog of propranolol. ORF 12592 caused concentration-dependent inhibition of isoproterenol stimulated adenylate cyclase activity in sarcolemma-enriched membrane preparations of guinea-pig myocardium. Its potency was slightly less than that of d,l-propranolol. ORF 12592 did not stimulate basal enzyme activity, suggesting it to be devoid of intrinsic sympathomimetic activity. It produced no marked inhibition of basal activity, nor did it inhibit sodium fluoride stimulated enzyme activity, indicating that the compound acts at the receptor rather than the catalytic site of the beta-adrenergic receptor-adenylate cyclase complex. ORF 12592 competed for binding of 3H-dihydroalprenolol to specific beta1 and beta2-adrenergic binding sites on turkey and leopard frog erythrocyte membranes respectively. Concentration-binding inhibition curves indicated that ORF 12592 is a non-selective beta-blocker with slightly less affinity for each beta-adrenergic receptor than propranolol."}
{"id": "PMID:28705", "title": "Bacteriologic flora of aspiration-induced pulmonary infections.", "content": "The role of anaerobic and aerobic microorganisms in the genesis of pneumonia or lung abscess in patients with historical, clinical, and radiologic findings suggestive of aspiration was compared to their role in similar patients without these findings. Bacterial specimens were obtained by transtracheal aspiration or thoracentesis. Anaerobes were isolated in 100% of the patients who were aspiration-prone as contrasted with only 20% of those who were not. Isolation of a single species or no growth was more common in the nonaspiration group, whereas multiple isolates were more common in the aspiration group. Patients with lung abscesses were treated with penicillin and all of them responded clinically, despite occasional recovery from the culture specimen of penicillin-resistant organisms. This suggests that lung abscess may be the result of a synergistic bacterial infection.", "contents": "Bacteriologic flora of aspiration-induced pulmonary infections. The role of anaerobic and aerobic microorganisms in the genesis of pneumonia or lung abscess in patients with historical, clinical, and radiologic findings suggestive of aspiration was compared to their role in similar patients without these findings. Bacterial specimens were obtained by transtracheal aspiration or thoracentesis. Anaerobes were isolated in 100% of the patients who were aspiration-prone as contrasted with only 20% of those who were not. Isolation of a single species or no growth was more common in the nonaspiration group, whereas multiple isolates were more common in the aspiration group. Patients with lung abscesses were treated with penicillin and all of them responded clinically, despite occasional recovery from the culture specimen of penicillin-resistant organisms. This suggests that lung abscess may be the result of a synergistic bacterial infection."}
{"id": "PMID:28706", "title": "Physician extenders in walk-in clinics: a prospective evaluation of the AMOSIST program.", "content": "The Automated Military Outpatient System (AMOS) Project was developed to improve the ambulatory care of patients with episodic and chronic illnesses. During the development of its episodic care component, the relative frequency of problems treated by the walk-in clinic staff was analyzed and showed a high volume of acute minor illnesses. A simple, conservative triage system run by non-professionals was developed to screen patients to a clinic for benign, self-limited illnesses run by physician-extenders. This group, the equivalent of civilian licensed practical nurses and nurses' aides, was trained in a task-oriented fashion to treat 44 common minor illnesses. Clinical algorithms for these illnesses were developed and used as training tools, memory aids, and auditing instruments. This program is now operating in 26 US Army hospitals and caring for some 44,000 patients a month in the continetal United States. We report the results of a prospective audit of the corpsmen and a study of the patient attitude and acceptance of the program.", "contents": "Physician extenders in walk-in clinics: a prospective evaluation of the AMOSIST program. The Automated Military Outpatient System (AMOS) Project was developed to improve the ambulatory care of patients with episodic and chronic illnesses. During the development of its episodic care component, the relative frequency of problems treated by the walk-in clinic staff was analyzed and showed a high volume of acute minor illnesses. A simple, conservative triage system run by non-professionals was developed to screen patients to a clinic for benign, self-limited illnesses run by physician-extenders. This group, the equivalent of civilian licensed practical nurses and nurses' aides, was trained in a task-oriented fashion to treat 44 common minor illnesses. Clinical algorithms for these illnesses were developed and used as training tools, memory aids, and auditing instruments. This program is now operating in 26 US Army hospitals and caring for some 44,000 patients a month in the continetal United States. We report the results of a prospective audit of the corpsmen and a study of the patient attitude and acceptance of the program."}
{"id": "PMID:28707", "title": "The glucose-pH relationship in parapneumonic effusions.", "content": "Both a low pleural fluid glucose concentration and pleural fluid acidosis are markers of severe pleural inflammation, but the relationship between these phenomena has not been defined clearly. Therefore, we measured simultaneous pleural fluid glucose concentrations and pH in 25 consecutive parapneumonic pleural fluids. Seventeen effusions had a glucose concentration greater than 60 mg/dl (group 1, 126 +/- 7 mg/dl, mean +/- SEM), while eight had a pleural fluid glucose less than 60 mg/dl (group 2, 15 +/- 3 mg/dl, P less than .01). Pleural fluid pH was 7.35 +/- 0.03 in group 1 compared with 6.83 +/- 0.09 in group 2 (P less than .01). A significant correlation between pleural fluid glucose and pH was found (r = .81, P less than .01). Low-glucose, low-pH effusions were complicated (either loculated or empyemas). Uncomplicated effusions had glucose concentrations greater than 60 mg/dl and a pleural fluid pH greater than 7.30. The concomitant occurrence of low pleural fluid glucose and pH suggests that the mechanisms leading to these phenomena are interrelated.", "contents": "The glucose-pH relationship in parapneumonic effusions. Both a low pleural fluid glucose concentration and pleural fluid acidosis are markers of severe pleural inflammation, but the relationship between these phenomena has not been defined clearly. Therefore, we measured simultaneous pleural fluid glucose concentrations and pH in 25 consecutive parapneumonic pleural fluids. Seventeen effusions had a glucose concentration greater than 60 mg/dl (group 1, 126 +/- 7 mg/dl, mean +/- SEM), while eight had a pleural fluid glucose less than 60 mg/dl (group 2, 15 +/- 3 mg/dl, P less than .01). Pleural fluid pH was 7.35 +/- 0.03 in group 1 compared with 6.83 +/- 0.09 in group 2 (P less than .01). A significant correlation between pleural fluid glucose and pH was found (r = .81, P less than .01). Low-glucose, low-pH effusions were complicated (either loculated or empyemas). Uncomplicated effusions had glucose concentrations greater than 60 mg/dl and a pleural fluid pH greater than 7.30. The concomitant occurrence of low pleural fluid glucose and pH suggests that the mechanisms leading to these phenomena are interrelated."}
{"id": "PMID:28708", "title": "Hyperparathyroidism, chemodectoma, thymoma, and myasthenia gravis.", "content": "Of two patients with hyperparathyroidism, one had an associated chemodectoma, and the other had a thymoma and myasthenia gravis. There is a possible relationship to the multiple endocrine neoplasia syndromes.", "contents": "Hyperparathyroidism, chemodectoma, thymoma, and myasthenia gravis. Of two patients with hyperparathyroidism, one had an associated chemodectoma, and the other had a thymoma and myasthenia gravis. There is a possible relationship to the multiple endocrine neoplasia syndromes."}
{"id": "PMID:28709", "title": "[The atrial arrhythmia syndrome of vagal origin].", "content": "Having observed 18 cases, the authors describe a syndrome of recurrent paroxysmal atrial arrhythmia which was very homogeneous from the clinical and ECG point of view. It was usually found in middle aged males, with no demonstrable underlying heart disease, whose disorder of intra-atrial conduction occurred during sinus rhythm. The condition developed slowly over the course of years towards a maximum incidence of several short daily attacks of an arrhythmia which alternated between an atrial fibrillation and atrial flutter. Vagal overactivity is the precipitating cause of these attacks which are usually not completely nocturnal. The condition never progressed to sino-atrial block nor to permanent fibrillation. The beginning of each attack, often heralded by atrial coupling with a long enough interval to cause re-entry, is accompanied by slowing of the sinus rate down to the threshold level. The vagal effect of shortening the action potential and refractory period is recognised to be non-homogeneous in the atrial wall, and suggests a re-entry mechanism rather than hyper-excitability. This would explain the usual resistance of atrial arrhythmias of vagal origin to digitalis, beta blockers and quinidine. Amiodarone alone is usually effective because of the prolongation of the action potential which it causes. In 5 particularly resistant cases a good clinical result was obtained by the insertion of an atrial pacemaker with a fairly rapid rate.", "contents": "[The atrial arrhythmia syndrome of vagal origin]. Having observed 18 cases, the authors describe a syndrome of recurrent paroxysmal atrial arrhythmia which was very homogeneous from the clinical and ECG point of view. It was usually found in middle aged males, with no demonstrable underlying heart disease, whose disorder of intra-atrial conduction occurred during sinus rhythm. The condition developed slowly over the course of years towards a maximum incidence of several short daily attacks of an arrhythmia which alternated between an atrial fibrillation and atrial flutter. Vagal overactivity is the precipitating cause of these attacks which are usually not completely nocturnal. The condition never progressed to sino-atrial block nor to permanent fibrillation. The beginning of each attack, often heralded by atrial coupling with a long enough interval to cause re-entry, is accompanied by slowing of the sinus rate down to the threshold level. The vagal effect of shortening the action potential and refractory period is recognised to be non-homogeneous in the atrial wall, and suggests a re-entry mechanism rather than hyper-excitability. This would explain the usual resistance of atrial arrhythmias of vagal origin to digitalis, beta blockers and quinidine. Amiodarone alone is usually effective because of the prolongation of the action potential which it causes. In 5 particularly resistant cases a good clinical result was obtained by the insertion of an atrial pacemaker with a fairly rapid rate."}
{"id": "PMID:28710", "title": "[Comparative study of acute poisonings in Belgian children and immigrant workers children].", "content": "This survey covers 786 children admitted with acute poisoning to the Saint-Pierre Hospital in Brussels between 1967 and 1976. The type and the frequency of products responsible for poisoning in the indigenous and immigrant children are compared. 45% of children admitted to hospital are immigrants but they constitute only 29% of the children admitted with poisoning. When compared with Belgian children, the immigrants more commonly ingest household products and ordinary drugs are taken more often than prescribed ones, but minor tranquillisers are particularly common. The socio-economic and psychologic factors responsible for these accidents are discussed and methods of prevention are suggested.", "contents": "[Comparative study of acute poisonings in Belgian children and immigrant workers children]. This survey covers 786 children admitted with acute poisoning to the Saint-Pierre Hospital in Brussels between 1967 and 1976. The type and the frequency of products responsible for poisoning in the indigenous and immigrant children are compared. 45% of children admitted to hospital are immigrants but they constitute only 29% of the children admitted with poisoning. When compared with Belgian children, the immigrants more commonly ingest household products and ordinary drugs are taken more often than prescribed ones, but minor tranquillisers are particularly common. The socio-economic and psychologic factors responsible for these accidents are discussed and methods of prevention are suggested."}
{"id": "PMID:28711", "title": "\"Akinetic depression\" in schizophrenia.", "content": "It is possible that some \"postpsychotic depressions\" may be a toxic effect of antipsychotic drugs. Out of a total of 94 schizophrenic patients, 28 developed a mild akinesia and 32 never developed extrapyramidal symptoms. Those who developed akinesia became less psychotic, but they also experienced a significant, although modest, increase in depression ratings. Successful treatment of the akinesia resulted in significant improvements in depression, somatic concern, anxiety, emotional withdrawal, blunted affect, and motor retardation on both physicians' and nurses' ratings. A high association between akinesia and both objectively rated and subjectively experienced sedative effect indicates that an 'akinetic depression' is not likely if the patient does not look or feel drowsy. The 32 nonakinetic patients also became less psychotic, but not more depressed.", "contents": "\"Akinetic depression\" in schizophrenia. It is possible that some \"postpsychotic depressions\" may be a toxic effect of antipsychotic drugs. Out of a total of 94 schizophrenic patients, 28 developed a mild akinesia and 32 never developed extrapyramidal symptoms. Those who developed akinesia became less psychotic, but they also experienced a significant, although modest, increase in depression ratings. Successful treatment of the akinesia resulted in significant improvements in depression, somatic concern, anxiety, emotional withdrawal, blunted affect, and motor retardation on both physicians' and nurses' ratings. A high association between akinesia and both objectively rated and subjectively experienced sedative effect indicates that an 'akinetic depression' is not likely if the patient does not look or feel drowsy. The 32 nonakinetic patients also became less psychotic, but not more depressed."}
{"id": "PMID:28716", "title": "[Barbexaclone in the treatment of cerebral dysrhythmia].", "content": "Forty two patients (22 adults and 20 children or adolescents) with cerebral dysrithmia were included in a therapeutic trial using barbexaclone: 28 patients suffered from grand mal crises, 2 had associated GM and petit mal and 12 showed disturbances of behaviour without clinical crises. The patients were observed from 6 to 13 months. Four patients failed to complete the trial due to various side effects; 25 patients with GM and 11 with behaviour disturbances showed a very good response; two patients with associated petit mal failed to show any improvement. Side effects such as insomnia and irritability were seen in 8 patients. The authors concluded that barbexaclone is an excellent therapeutic agent in the treatment of grand mal and in patients with behaviour disturbances without convulsive crises.", "contents": "[Barbexaclone in the treatment of cerebral dysrhythmia]. Forty two patients (22 adults and 20 children or adolescents) with cerebral dysrithmia were included in a therapeutic trial using barbexaclone: 28 patients suffered from grand mal crises, 2 had associated GM and petit mal and 12 showed disturbances of behaviour without clinical crises. The patients were observed from 6 to 13 months. Four patients failed to complete the trial due to various side effects; 25 patients with GM and 11 with behaviour disturbances showed a very good response; two patients with associated petit mal failed to show any improvement. Side effects such as insomnia and irritability were seen in 8 patients. The authors concluded that barbexaclone is an excellent therapeutic agent in the treatment of grand mal and in patients with behaviour disturbances without convulsive crises."}
{"id": "PMID:28713", "title": "[The in-vivo effect of dihydroergocristine on human platelet function].", "content": "An acute test was run on healthy volunteers to assess the effect of i.v. dihydroergocristine methansulphonate on platelet function. The number of platelets was virtually unaffected, whereas adhesion to glass was significantly reduced. A direct and specific effect was noted on the 1st, adrenaline aggregation wave, while the 2nd wave (expression of ADP) induced aggregation did not appear to have been significantly altered. It is felt that further examination of the alpha-adrenergic block induced by the drug should be under-taken in view of the recent literature data which explain the inability of commonly employed anti-aggreganting drugs, such as acetylsalicylic acid, to prevent and treat atherothrombosis, in spite of the encouraging experimental results.", "contents": "[The in-vivo effect of dihydroergocristine on human platelet function]. An acute test was run on healthy volunteers to assess the effect of i.v. dihydroergocristine methansulphonate on platelet function. The number of platelets was virtually unaffected, whereas adhesion to glass was significantly reduced. A direct and specific effect was noted on the 1st, adrenaline aggregation wave, while the 2nd wave (expression of ADP) induced aggregation did not appear to have been significantly altered. It is felt that further examination of the alpha-adrenergic block induced by the drug should be under-taken in view of the recent literature data which explain the inability of commonly employed anti-aggreganting drugs, such as acetylsalicylic acid, to prevent and treat atherothrombosis, in spite of the encouraging experimental results."}
{"id": "PMID:28721", "title": "Corrosive injury of the esophagus. Result of ingesting some denture cleanser tablets and powder.", "content": "Denture cleansers are ubiquitous compounds frequently found in the household. Experimental studies were carried out to investigate the caustic, chemical, and histopathological properties of Polident and Efferdent tablets and Ansodent powder. All products were found to have caused severe focal to diffuse caustic burns of the esophagus due to the concentration of hydrogen peroxide that was liberated by these compounds.", "contents": "Corrosive injury of the esophagus. Result of ingesting some denture cleanser tablets and powder. Denture cleansers are ubiquitous compounds frequently found in the household. Experimental studies were carried out to investigate the caustic, chemical, and histopathological properties of Polident and Efferdent tablets and Ansodent powder. All products were found to have caused severe focal to diffuse caustic burns of the esophagus due to the concentration of hydrogen peroxide that was liberated by these compounds."}
{"id": "PMID:28723", "title": "Effects of xylazine hydrochloride on urine in cattle.", "content": "Urine volume, urine pH, and urine glucose concentration were monitored for up to 24 hours after physiological saline or one of two dosage levels (0.22 mg/kg or 0.44 mg/kg) of xylazine was administered to cows. During the first 2 hours after xylazine was given, urine output was greatly increased (relative to the control animals), with the high dosage group having more output than the low dosage group. The influence of the drug on urine volume had ended by 5 hours after injection when urine output in both dosage groups had returned to that of the control group. Glucose was detected in the urine of xylazine treated animals, beginning at 15 to 30 minutes after injection, reached a maximum at 2 hours, and was undetectable at 5 to 6 hours. Urine pH decreased in control and treated animals, but in treated animals the pH began to increase 2 hr after treatment.", "contents": "Effects of xylazine hydrochloride on urine in cattle. Urine volume, urine pH, and urine glucose concentration were monitored for up to 24 hours after physiological saline or one of two dosage levels (0.22 mg/kg or 0.44 mg/kg) of xylazine was administered to cows. During the first 2 hours after xylazine was given, urine output was greatly increased (relative to the control animals), with the high dosage group having more output than the low dosage group. The influence of the drug on urine volume had ended by 5 hours after injection when urine output in both dosage groups had returned to that of the control group. Glucose was detected in the urine of xylazine treated animals, beginning at 15 to 30 minutes after injection, reached a maximum at 2 hours, and was undetectable at 5 to 6 hours. Urine pH decreased in control and treated animals, but in treated animals the pH began to increase 2 hr after treatment."}
{"id": "PMID:28725", "title": "A characterization of the nucleotide uptake of chromaffin granules of bovine adrenal medulla.", "content": "Chromaffin granules isolated from bovine adrenal gland were incubated with (3)H-labelled nucleotides and [(14)C]noradrenaline to study the uptake of these substances. [(3)H]ATP, [(3)H]ADP and [(3)H]AMP are taken up by these organelles by the same temperature-dependent mechanism. The apparent K(m) for ATP and ADP is 1.4mm, and for AMP it is 2.9mm. The uptake of ATP has a flat pH optimum, whereas the catecholamine uptake increases with more alkaline pH. Atractyloside and carboxyatractyloside are competitive and specific inhibitors of nucleotide uptake, whereas reserpine inhibits only that for catecholamines. Mg(2+) ions activate uptake of both catecholamine and nucleotides, whereas EDTA and N-ethylmaleimide inhibit these processes. Nucleotide and catecholamine uptakes are inhibited by uncouplers of oxidative phosphorylation and by two ATP analogues. NH(4) (+) ions and nigericin in the presence of KCl inhibit only catecholamine uptake. It is concluded that nucleotide uptake, as proposed previously for catecholamine uptake, depends on an electrochemical proton gradient produced by a proton-translocating adenosine triphosphatase localized in the membrane of chromaffin granules. Furthermore, as suggested by the effect of NH(4) (+) and nigericin, catecholamine uptake apparently depends on the chemical part of this gradient, whereas the results for nucleotide uptake are consistent with its dependence on the electrical component.", "contents": "A characterization of the nucleotide uptake of chromaffin granules of bovine adrenal medulla. Chromaffin granules isolated from bovine adrenal gland were incubated with (3)H-labelled nucleotides and [(14)C]noradrenaline to study the uptake of these substances. [(3)H]ATP, [(3)H]ADP and [(3)H]AMP are taken up by these organelles by the same temperature-dependent mechanism. The apparent K(m) for ATP and ADP is 1.4mm, and for AMP it is 2.9mm. The uptake of ATP has a flat pH optimum, whereas the catecholamine uptake increases with more alkaline pH. Atractyloside and carboxyatractyloside are competitive and specific inhibitors of nucleotide uptake, whereas reserpine inhibits only that for catecholamines. Mg(2+) ions activate uptake of both catecholamine and nucleotides, whereas EDTA and N-ethylmaleimide inhibit these processes. Nucleotide and catecholamine uptakes are inhibited by uncouplers of oxidative phosphorylation and by two ATP analogues. NH(4) (+) ions and nigericin in the presence of KCl inhibit only catecholamine uptake. It is concluded that nucleotide uptake, as proposed previously for catecholamine uptake, depends on an electrochemical proton gradient produced by a proton-translocating adenosine triphosphatase localized in the membrane of chromaffin granules. Furthermore, as suggested by the effect of NH(4) (+) and nigericin, catecholamine uptake apparently depends on the chemical part of this gradient, whereas the results for nucleotide uptake are consistent with its dependence on the electrical component."}
{"id": "PMID:28726", "title": "Pyruvate and ketone-body transport across the mitochondrial membrane. Exchange properties, pH-dependence and mechanism of the carrier.", "content": "The effects of exchangeable ions and pH on the efflux of pyruvate from preloaded mitochondria are reported. Efflux obeys first-order kinetics, and the stimulation of efflux by exchangeable ions such as acetoacetate and lactate obeys Michaelis--Menten kinetics. The apparent Km value +/- S.E. for acetoacetate was 0.56 +/- 0.14 mM (n = 5) and that for lactate 12.3 +/- 2.3 mM (n = 6). The Vmax. values +/- S.E. at 0 degrees C were 16.2 +/- 2.0 and 21.9 +/- 2.7 nmol/min per mg of protein. The exchange of a variety of other substituted monocarboxylates was also studied. Efflux was also stimulated by increasing the external pH. The data gave a pK for the transport process of 8.35 and a Vmax. of 3.31 +/- 0.14 nmol/min per mg. The similarity of the Vmax. values for various exchangeable ions but the difference of this from the Vmax. in the absence of exchangeable ions may indicate that transport of pyruvate occurs with H+ and not in exchange for an OH- ion. The inhibition of transport by alpha-cyano-4-hydroxycinnamate took several seconds to reach completion at 0 degrees C. It is proposed that inhibition occurs by binding to the substrate site and subsequent reaction with an -SH group on the inside of the membrane. The inhibitor can be displaced by substrates that can also enter the mitochondria independently of the carrier and so compete with the inhibitor for the substrate-binding site on the inside of the membrane. A mechanism for transport is proposed that invokes a transition state of pyruvate involving addition of an -SH group to the 2-carbon of pyruvate. Evidence is presented that suggests that ketone bodies may cross the mitochondrial membrane either on the carrier or by free diffusion. The physiological involvement of the carrier in ketone-body metabolism is discussed. The role of ketone bodies and pH in the physiological regulation of pyruvate transport is considered.", "contents": "Pyruvate and ketone-body transport across the mitochondrial membrane. Exchange properties, pH-dependence and mechanism of the carrier. The effects of exchangeable ions and pH on the efflux of pyruvate from preloaded mitochondria are reported. Efflux obeys first-order kinetics, and the stimulation of efflux by exchangeable ions such as acetoacetate and lactate obeys Michaelis--Menten kinetics. The apparent Km value +/- S.E. for acetoacetate was 0.56 +/- 0.14 mM (n = 5) and that for lactate 12.3 +/- 2.3 mM (n = 6). The Vmax. values +/- S.E. at 0 degrees C were 16.2 +/- 2.0 and 21.9 +/- 2.7 nmol/min per mg of protein. The exchange of a variety of other substituted monocarboxylates was also studied. Efflux was also stimulated by increasing the external pH. The data gave a pK for the transport process of 8.35 and a Vmax. of 3.31 +/- 0.14 nmol/min per mg. The similarity of the Vmax. values for various exchangeable ions but the difference of this from the Vmax. in the absence of exchangeable ions may indicate that transport of pyruvate occurs with H+ and not in exchange for an OH- ion. The inhibition of transport by alpha-cyano-4-hydroxycinnamate took several seconds to reach completion at 0 degrees C. It is proposed that inhibition occurs by binding to the substrate site and subsequent reaction with an -SH group on the inside of the membrane. The inhibitor can be displaced by substrates that can also enter the mitochondria independently of the carrier and so compete with the inhibitor for the substrate-binding site on the inside of the membrane. A mechanism for transport is proposed that invokes a transition state of pyruvate involving addition of an -SH group to the 2-carbon of pyruvate. Evidence is presented that suggests that ketone bodies may cross the mitochondrial membrane either on the carrier or by free diffusion. The physiological involvement of the carrier in ketone-body metabolism is discussed. The role of ketone bodies and pH in the physiological regulation of pyruvate transport is considered."}
{"id": "PMID:28727", "title": "Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats.", "content": "Glucagon treatment of rats allowed the isolation of liver mitochondria with enhanced rates of pyruvate metabolism measured in either sucrose or KCl media. No change in the activity of the pyruvate carrier itself was apparent, but under metabolizing conditions, use of the inhibitor of pyruvate transport, alpha-cyano-4-hydroxycinnamate, demonstrated that pyruvate transport limited the rate of pyruvate metabolism. The maximum rate of transport under metabolizing conditions was enhanced by glucagon treatment. Problems involved in measuring the transmembrane pH gradient under metabolizing conditions are discussed and a variety of techniques are used to estimate the matrix pH. From the distribution of methylamine, ammonia and D-lactate and the Ki for inhibition by alpha-cyano-4-hydroxycinnamate it is concluded that the matrix is more acid than the medium and that the pH of the matrix rises after glucagon treatment. The increase in matrix pH stimulates pyruvate transport. The membrane potential, ATP concentration and O2 uptake were also increased under metabolizing conditions in glucagon-treated mitochondria. These changes were correlated with a stimulation of the respiratory chain which can be observed in uncoupled mitochondria [Yamazaki (1975) J. Biol. Chem. 250, 7924--7930]. The mitochondrial Mg2+ content (mean +/- S.E.M.) was increased from 38.8 +/- 1.2 (n = 26) to 47.5 +/- 2.0 (n = 26) ng-atoms/mg by glucagon and the K+ content from 126.7 +/- 10.3 (n = 19) ng-atoms/mg. This may represent a change in membrane potential induced by glucagon in vivo. The physiological significance of these results in the control of gluconeogenesis is discussed.", "contents": "Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats. Glucagon treatment of rats allowed the isolation of liver mitochondria with enhanced rates of pyruvate metabolism measured in either sucrose or KCl media. No change in the activity of the pyruvate carrier itself was apparent, but under metabolizing conditions, use of the inhibitor of pyruvate transport, alpha-cyano-4-hydroxycinnamate, demonstrated that pyruvate transport limited the rate of pyruvate metabolism. The maximum rate of transport under metabolizing conditions was enhanced by glucagon treatment. Problems involved in measuring the transmembrane pH gradient under metabolizing conditions are discussed and a variety of techniques are used to estimate the matrix pH. From the distribution of methylamine, ammonia and D-lactate and the Ki for inhibition by alpha-cyano-4-hydroxycinnamate it is concluded that the matrix is more acid than the medium and that the pH of the matrix rises after glucagon treatment. The increase in matrix pH stimulates pyruvate transport. The membrane potential, ATP concentration and O2 uptake were also increased under metabolizing conditions in glucagon-treated mitochondria. These changes were correlated with a stimulation of the respiratory chain which can be observed in uncoupled mitochondria [Yamazaki (1975) J. Biol. Chem. 250, 7924--7930]. The mitochondrial Mg2+ content (mean +/- S.E.M.) was increased from 38.8 +/- 1.2 (n = 26) to 47.5 +/- 2.0 (n = 26) ng-atoms/mg by glucagon and the K+ content from 126.7 +/- 10.3 (n = 19) ng-atoms/mg. This may represent a change in membrane potential induced by glucagon in vivo. The physiological significance of these results in the control of gluconeogenesis is discussed."}
{"id": "PMID:28728", "title": "Kinetics of liver microsomal cholecalciferol 25-hydroxylase in vitamin D-depleted and -repleated rats.", "content": "Kinetics of vitamin D-depleted and -repleted rat liver microsomal cholecalciferol 25-hydroxylase were studied. Anaerobiosis, CO, omission of a NADPH-generating system and addition of detergents all decreased the activities, showing that the hydroxylase behaves like a cytochrome P-450-dependent enzyme. An apparent Km of 0.18 micrometer and Vmax. of 32pmol/min per g of tissue were found for vitamin D-deficient animals. Although both apparent Km and Vmax. were significantly altered in vitamin D-repleted animals no inhibition of the enzyme was elicited. These latter results show that at normal vitamin D intake, rat liver cholecalciferol 25-hydroxylase is not feedback-inhibited.", "contents": "Kinetics of liver microsomal cholecalciferol 25-hydroxylase in vitamin D-depleted and -repleated rats. Kinetics of vitamin D-depleted and -repleted rat liver microsomal cholecalciferol 25-hydroxylase were studied. Anaerobiosis, CO, omission of a NADPH-generating system and addition of detergents all decreased the activities, showing that the hydroxylase behaves like a cytochrome P-450-dependent enzyme. An apparent Km of 0.18 micrometer and Vmax. of 32pmol/min per g of tissue were found for vitamin D-deficient animals. Although both apparent Km and Vmax. were significantly altered in vitamin D-repleted animals no inhibition of the enzyme was elicited. These latter results show that at normal vitamin D intake, rat liver cholecalciferol 25-hydroxylase is not feedback-inhibited."}
{"id": "PMID:28729", "title": "The uptake of silicic acid by rat liver mitochondria.", "content": "1. To gain insight into a putative role for mitochondria in silicon metabolism, mitochondrial uptake (by which it is meant the removal from the medium) of silicic acid [Si(OH)4] was studied under conditions minimizing SI(OH)4 polymerization. 2. Measurements of mitochondrial respiration and swelling indicated indirectly a significant uptake of Si(OH)4 as a weak acid, but this was not confirmed when 31Si(OH)4 was used as a tracer. 31Si(OH)4 occupied a mitochondrial volume similar to that of 3H2O and was relatively unaffected by mitochondrial energy status and by the pH gradient across the mitochondrial inner membrane. 3. Uptake was directly proportional to Si(OH)4 concentration in the range 0-3 mM. 4. The uptake consisted of two components: under all conditions examined, the greater quantity, amounting to 1-2nmol of Si(OH)4/mg of mitochondrial protein, was bound, a major portion of it external to the inner membrane, with the lesser quantity free within the matrix space. 5. Equilibration of 31Si(OH)4 between medium and matrix was a slow process, having a half-time of approx. 10 min at 22 degrees C. 6. Mersalyl and N-ethylmaleimide inhibited the uptake by preferentially lowering the amount of Si(OH)4 bound. Their action was somewhat variable, depending on the precise nature of the suspending medium, and suggesting that the bound material may represent polymerized forms of Si(OH)4. 7. It is concluded that Si(OH)4 may penetrate the mitochondrial inner membrane by a simple diffusion mechanism.", "contents": "The uptake of silicic acid by rat liver mitochondria. 1. To gain insight into a putative role for mitochondria in silicon metabolism, mitochondrial uptake (by which it is meant the removal from the medium) of silicic acid [Si(OH)4] was studied under conditions minimizing SI(OH)4 polymerization. 2. Measurements of mitochondrial respiration and swelling indicated indirectly a significant uptake of Si(OH)4 as a weak acid, but this was not confirmed when 31Si(OH)4 was used as a tracer. 31Si(OH)4 occupied a mitochondrial volume similar to that of 3H2O and was relatively unaffected by mitochondrial energy status and by the pH gradient across the mitochondrial inner membrane. 3. Uptake was directly proportional to Si(OH)4 concentration in the range 0-3 mM. 4. The uptake consisted of two components: under all conditions examined, the greater quantity, amounting to 1-2nmol of Si(OH)4/mg of mitochondrial protein, was bound, a major portion of it external to the inner membrane, with the lesser quantity free within the matrix space. 5. Equilibration of 31Si(OH)4 between medium and matrix was a slow process, having a half-time of approx. 10 min at 22 degrees C. 6. Mersalyl and N-ethylmaleimide inhibited the uptake by preferentially lowering the amount of Si(OH)4 bound. Their action was somewhat variable, depending on the precise nature of the suspending medium, and suggesting that the bound material may represent polymerized forms of Si(OH)4. 7. It is concluded that Si(OH)4 may penetrate the mitochondrial inner membrane by a simple diffusion mechanism."}
{"id": "PMID:28730", "title": "The nature of the allosteric interactions of ribonuclease and its ligands.", "content": "The allosteric model for ribonuclease activity by Walker, Ralston & Darvey [(1975) Biochem.J. 147, 425--433; (1976) Biochem.J. 153, 329--337] involves the binding of a large number of molecules of substrate or substrate analogue to a series of allosteric sites on the enzyme. In the present paper, the nature of these allosteric interactions is investigated. The effects of ionic strength pH carbamoylation of lysine to homocitrulline and of deamidation of glutamine and asparagine on plots of velocity versus substrate concentration are examined and evidence is presented that the allosteric transition involves an electrostatic interaction between the negatively charged substrate molecules and the cationic groups on the enzyme.", "contents": "The nature of the allosteric interactions of ribonuclease and its ligands. The allosteric model for ribonuclease activity by Walker, Ralston & Darvey [(1975) Biochem.J. 147, 425--433; (1976) Biochem.J. 153, 329--337] involves the binding of a large number of molecules of substrate or substrate analogue to a series of allosteric sites on the enzyme. In the present paper, the nature of these allosteric interactions is investigated. The effects of ionic strength pH carbamoylation of lysine to homocitrulline and of deamidation of glutamine and asparagine on plots of velocity versus substrate concentration are examined and evidence is presented that the allosteric transition involves an electrostatic interaction between the negatively charged substrate molecules and the cationic groups on the enzyme."}
{"id": "PMID:28731", "title": "Periodate oxidation and the shapes of glycosaminoglycuronans in solution.", "content": "1. It is proposed that periodate oxidation of glycol groups in the repeating units of polysaccharide molecules can be used to probe differences in polymer shapes in solution. 2. Measurement of second-order rate constants (k2) of periodate-glycol reactions may be compared between polymers and relevant monomers, to assess perturbations due to polymer configuration. 3. Factors effecting the measurement and interpretation of k2 are discussed. Over-oxidation, free-radical side reactions, end-group effects, Donnan equilibria and polymer (or molecular-weight) effects are relevant, but their importance is either small or can be minimized in practice. 4. A small group of glycosaminoglycuronans (chondroitin 4- and 6-sulphates and hyaluronate) are oxidized 50--100 times more slowly than three other glycosaminoglycuronans of similar composition, relevant monomers or three homopolyuronides. 5. A stable configuration in solution is postulated for the periodate-resistant polymers, involving carboxylate, acetamido and hydroxy groups in hydrogen-bonded sequences on alternate sides of the molecule. The more easily oxidizable polyuronides are unable to form this configuration. 6. The effect of temperature on the postulated configuration is investigated through the Arrhenius plot of k2, measured to hyaluronate, chondroitin 6-sulphate and methyl 4-O-methyl-alpha-D-glucopyranoside. Probable transitions at high (around 90 degrees C) temperatures were observed for both polymers, with an additional transition at about 37 degrees C in the case of hyaluronate. 7. L-Iduronic acid can take up different conformations depending on the polymer environment.", "contents": "Periodate oxidation and the shapes of glycosaminoglycuronans in solution. 1. It is proposed that periodate oxidation of glycol groups in the repeating units of polysaccharide molecules can be used to probe differences in polymer shapes in solution. 2. Measurement of second-order rate constants (k2) of periodate-glycol reactions may be compared between polymers and relevant monomers, to assess perturbations due to polymer configuration. 3. Factors effecting the measurement and interpretation of k2 are discussed. Over-oxidation, free-radical side reactions, end-group effects, Donnan equilibria and polymer (or molecular-weight) effects are relevant, but their importance is either small or can be minimized in practice. 4. A small group of glycosaminoglycuronans (chondroitin 4- and 6-sulphates and hyaluronate) are oxidized 50--100 times more slowly than three other glycosaminoglycuronans of similar composition, relevant monomers or three homopolyuronides. 5. A stable configuration in solution is postulated for the periodate-resistant polymers, involving carboxylate, acetamido and hydroxy groups in hydrogen-bonded sequences on alternate sides of the molecule. The more easily oxidizable polyuronides are unable to form this configuration. 6. The effect of temperature on the postulated configuration is investigated through the Arrhenius plot of k2, measured to hyaluronate, chondroitin 6-sulphate and methyl 4-O-methyl-alpha-D-glucopyranoside. Probable transitions at high (around 90 degrees C) temperatures were observed for both polymers, with an additional transition at about 37 degrees C in the case of hyaluronate. 7. L-Iduronic acid can take up different conformations depending on the polymer environment."}
{"id": "PMID:28732", "title": "The enzymes of proline biosynthesis in Escherichia coli. Their molecular weights and the problem of enzyme aggregation.", "content": "1. By using Bio-Gel A1.5M and Sephadex G-150 columns, crude cell-free extracts of Escherichia coli were fractionated to demonstrate the existence of a proline-biosynthetic aggregate. 2. Sephadex G-150 resolves two glutamyl kinases that are inhibited by proline, with mol.wts. of 125000 and 38000, the reactions of which are Mg2+-dependent. The heavier species is more sensitive to inhibition by proline. 3. Gamma-Glutamyl phosphate reductase and 1-pyrroline-5-carboxylate reductase (EC 1.5.1.2) have mol.wts. of approx. 125000 and 190000 respectively, the specific activity of the latter being 5 X 10(3)-fold greater than either of the other two biosynthetic enzymes or of the total pathway in vivo. 4. Bio-Gel A1.5M chromatography gave a single glutamyl kinase of mol.wt. 250000, and the possibility of this being a constituent of an enzyme complex is discussed.", "contents": "The enzymes of proline biosynthesis in Escherichia coli. Their molecular weights and the problem of enzyme aggregation. 1. By using Bio-Gel A1.5M and Sephadex G-150 columns, crude cell-free extracts of Escherichia coli were fractionated to demonstrate the existence of a proline-biosynthetic aggregate. 2. Sephadex G-150 resolves two glutamyl kinases that are inhibited by proline, with mol.wts. of 125000 and 38000, the reactions of which are Mg2+-dependent. The heavier species is more sensitive to inhibition by proline. 3. Gamma-Glutamyl phosphate reductase and 1-pyrroline-5-carboxylate reductase (EC 1.5.1.2) have mol.wts. of approx. 125000 and 190000 respectively, the specific activity of the latter being 5 X 10(3)-fold greater than either of the other two biosynthetic enzymes or of the total pathway in vivo. 4. Bio-Gel A1.5M chromatography gave a single glutamyl kinase of mol.wt. 250000, and the possibility of this being a constituent of an enzyme complex is discussed."}
{"id": "PMID:28733", "title": "pH-dependent changes of intrinsic fluorescence of chemically modified liver alcohol dehydrogenases.", "content": "Horse liver alcohol dehydrogenase specifically carboxymethylated on cysteine-46 (a ligand to the zinc in the active site) or acetimidylated on 25 of the 30 lysine residues per subunit (including residue 228) was studied. The tryptophan fluorescence of these enzymes decreased by 35% as pH was increased, with an apparent pKa of 9.8 +/- 0.2, identical with that of native enzyme. Native enzyme in the presence of 30mM-imidazole, which displaces a water molecule ligated to the zinc, also had a pKa of 9.8. The ionoizable group is thus neither the water molecule nor one of the modified groups. Binding of NAD+ shifted the pKa for the fluorescence transition to 7.6 with native enzyme and to 9.0 with acetimidylated enzyme, but did not shift the pKa of carboxymethylated enzyme. Binding of NAD+ and trifluoroethanol, an unreactive alcohol, gave maximal fluorescence quenching at pH7 with all three enzymes. The acetimidylated enzyme--NAD+--trifluoroethanol complex had an apparent pKa of 5.0, but the pK of the native enzyme complex was experimentally inaccessible. The results are interpreted in terms of coupled equilibria between two different conformational states. On binding of NAD+, the modified enzymes apparently change conformation less readily than does native enzyme, but binding of alcohol can drive the change to completion.", "contents": "pH-dependent changes of intrinsic fluorescence of chemically modified liver alcohol dehydrogenases. Horse liver alcohol dehydrogenase specifically carboxymethylated on cysteine-46 (a ligand to the zinc in the active site) or acetimidylated on 25 of the 30 lysine residues per subunit (including residue 228) was studied. The tryptophan fluorescence of these enzymes decreased by 35% as pH was increased, with an apparent pKa of 9.8 +/- 0.2, identical with that of native enzyme. Native enzyme in the presence of 30mM-imidazole, which displaces a water molecule ligated to the zinc, also had a pKa of 9.8. The ionoizable group is thus neither the water molecule nor one of the modified groups. Binding of NAD+ shifted the pKa for the fluorescence transition to 7.6 with native enzyme and to 9.0 with acetimidylated enzyme, but did not shift the pKa of carboxymethylated enzyme. Binding of NAD+ and trifluoroethanol, an unreactive alcohol, gave maximal fluorescence quenching at pH7 with all three enzymes. The acetimidylated enzyme--NAD+--trifluoroethanol complex had an apparent pKa of 5.0, but the pK of the native enzyme complex was experimentally inaccessible. The results are interpreted in terms of coupled equilibria between two different conformational states. On binding of NAD+, the modified enzymes apparently change conformation less readily than does native enzyme, but binding of alcohol can drive the change to completion."}
{"id": "PMID:28734", "title": "The inactivation of native enzymes by a neutral proteinase from rat intestinal muscle.", "content": "1. The solubilization and partial purification of a proteinase from the intestinal smooth muscle of rats fed on protein-free diets are described. 2. It has a mol.wt. of about 33000 and it is stable over a narrow pH range. 3. From its susceptibility to known modifers of proteolytic enzymes, it appears to be a serine proteinase of a trypsin-like nature. Active-site titration with soya-bean trypsin inhibitor shows that the concentration of proteinase was about 3 microgram/g wet wt. of intestinal smooth muscle. However, the muscle proteinase demonstrates a marked ability for inactivating enzymes in their native conformation at neutral pH. It is about 100 times more efficient than pancreatic trypsin when the inactivating activities are compared on an approximately equimolar basis. 4. Inactivation of the substrate enzymes is accompanied by limited proteolysis, as demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 5. An endogenous inhibitor was separated from the proteinase by fractionation with (NH4)2SO4. 6. Contamination of the muscle tissue by lumen, mucosal or blood proteinases and inhibitors is shown to be unlikely. 7. A role for the neutral trypsin-like proteinase in initiating the degradation of intracellular enzymes is considered.", "contents": "The inactivation of native enzymes by a neutral proteinase from rat intestinal muscle. 1. The solubilization and partial purification of a proteinase from the intestinal smooth muscle of rats fed on protein-free diets are described. 2. It has a mol.wt. of about 33000 and it is stable over a narrow pH range. 3. From its susceptibility to known modifers of proteolytic enzymes, it appears to be a serine proteinase of a trypsin-like nature. Active-site titration with soya-bean trypsin inhibitor shows that the concentration of proteinase was about 3 microgram/g wet wt. of intestinal smooth muscle. However, the muscle proteinase demonstrates a marked ability for inactivating enzymes in their native conformation at neutral pH. It is about 100 times more efficient than pancreatic trypsin when the inactivating activities are compared on an approximately equimolar basis. 4. Inactivation of the substrate enzymes is accompanied by limited proteolysis, as demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 5. An endogenous inhibitor was separated from the proteinase by fractionation with (NH4)2SO4. 6. Contamination of the muscle tissue by lumen, mucosal or blood proteinases and inhibitors is shown to be unlikely. 7. A role for the neutral trypsin-like proteinase in initiating the degradation of intracellular enzymes is considered."}
{"id": "PMID:28735", "title": "Kinetics and mechanism of the rat brain phenol sulphotransferase reaction.", "content": "Some properties of rat brain phenol sulphotransferase were investigated in in vitro at pH7.4. The enzyme was purified 10-fold by chromatography on DEAE-Sephadex -50. It can be assayed with 4-hydroxy-3-methoxyphenylethylene glycol or 4-methylumbelliferone as the sulphate acceptor. The partially purified enzyme is stable for at least 1 week when stored at 4 degrees C. It is, however, additionally activated (10--20%) and stabilized by 1 mM-dithiothreitol. The activity of the enzyme does not depend on the addition of exogenous Mg2+. The pH optima for the sulphation of 4-hydroxy-3-methoxyphenylethylene glycol and 4-methylumbelliferone are 7.8 and 7.4 respectively. Substrate inhibition by the sulphate acceptor is apparent at concentrations over 0.05mM. Initial-velocity studies in the absence and presence of product and dead-end inhibitors suggested that the mechanism of the rat brain sulphotransferase reaction is sequential ordered Bi Bi with a dead-end complex of enzyme with adenosine 3',5'-biphosphate and sulphate acceptor. The sulphate donor adenosine 3'-phosphate 5'-sulphatophosphate is the first substrate that adds to the enzyme, and the sulphate acceptor is the second substrate. The dissociation constant for the complex of enzyme with sulphate donor is 21 micron. The sulphated substrate is the first product and adenosine 3',5'-biphosphate is the second product that leaves the enzyme.", "contents": "Kinetics and mechanism of the rat brain phenol sulphotransferase reaction. Some properties of rat brain phenol sulphotransferase were investigated in in vitro at pH7.4. The enzyme was purified 10-fold by chromatography on DEAE-Sephadex -50. It can be assayed with 4-hydroxy-3-methoxyphenylethylene glycol or 4-methylumbelliferone as the sulphate acceptor. The partially purified enzyme is stable for at least 1 week when stored at 4 degrees C. It is, however, additionally activated (10--20%) and stabilized by 1 mM-dithiothreitol. The activity of the enzyme does not depend on the addition of exogenous Mg2+. The pH optima for the sulphation of 4-hydroxy-3-methoxyphenylethylene glycol and 4-methylumbelliferone are 7.8 and 7.4 respectively. Substrate inhibition by the sulphate acceptor is apparent at concentrations over 0.05mM. Initial-velocity studies in the absence and presence of product and dead-end inhibitors suggested that the mechanism of the rat brain sulphotransferase reaction is sequential ordered Bi Bi with a dead-end complex of enzyme with adenosine 3',5'-biphosphate and sulphate acceptor. The sulphate donor adenosine 3'-phosphate 5'-sulphatophosphate is the first substrate that adds to the enzyme, and the sulphate acceptor is the second substrate. The dissociation constant for the complex of enzyme with sulphate donor is 21 micron. The sulphated substrate is the first product and adenosine 3',5'-biphosphate is the second product that leaves the enzyme."}
{"id": "PMID:28736", "title": "Inactivation of glutamate dehydrogenase and glutamate synthase from Bacillus megaterium by phenylglyoxal, butane-2,3-dione and pyridoxal 5'-phosphate.", "content": "Reaction of phenylglyoxal with glutamate dehydrogenase (EC 1.4.1.4), but not with glutamate synthase (EC 2.6.1.53), from Bacillus megaterium resulted in complete loss of enzyme activity. NADPH alone or together with 2-oxoglutarate provided substantial protection from inactivation by phenylglyoxal. Some 2mol of [14C]Phenylglyoxal was incorporated/mol of subunit of glutamate dehydrogenase. Addition of 1mM-NADPH decreased incorporation by 0.7mol. The Ki for phenylglyoxal was 6.7mM and Ks for competition with NADPH was 0.5mM. Complete inactivation of glutamate dehydrogenase by butane-2,3-dione was estimated by extrapolation to result from the loss of 3 of the 19 arginine residues/subunit. NADPH, but not NADH, provided almost complete protection against inactivation. Butane-2,3-dione had only a slight inactivating effect on glutamate synthase. The data suggest that an essential arginine residue may be involved in the binding of NADPH to glutamate dehydrogenase. The enzymes were inactivated by pyridoxal 5'-phosphate and this inactivation increased 3--4-fold in the borate buffer. NADPH completely prevented inactivation by pyridoxal 5'-phosphate.", "contents": "Inactivation of glutamate dehydrogenase and glutamate synthase from Bacillus megaterium by phenylglyoxal, butane-2,3-dione and pyridoxal 5'-phosphate. Reaction of phenylglyoxal with glutamate dehydrogenase (EC 1.4.1.4), but not with glutamate synthase (EC 2.6.1.53), from Bacillus megaterium resulted in complete loss of enzyme activity. NADPH alone or together with 2-oxoglutarate provided substantial protection from inactivation by phenylglyoxal. Some 2mol of [14C]Phenylglyoxal was incorporated/mol of subunit of glutamate dehydrogenase. Addition of 1mM-NADPH decreased incorporation by 0.7mol. The Ki for phenylglyoxal was 6.7mM and Ks for competition with NADPH was 0.5mM. Complete inactivation of glutamate dehydrogenase by butane-2,3-dione was estimated by extrapolation to result from the loss of 3 of the 19 arginine residues/subunit. NADPH, but not NADH, provided almost complete protection against inactivation. Butane-2,3-dione had only a slight inactivating effect on glutamate synthase. The data suggest that an essential arginine residue may be involved in the binding of NADPH to glutamate dehydrogenase. The enzymes were inactivated by pyridoxal 5'-phosphate and this inactivation increased 3--4-fold in the borate buffer. NADPH completely prevented inactivation by pyridoxal 5'-phosphate."}
{"id": "PMID:28737", "title": "Properties of matrix-bound dimer and monomer derivatives of immobilized creatine kinase from rabbit skeletal muscle.", "content": "Dimeric creatine kinase (EC 2.7.3.2) from rabbit skeletal muscle can be immobilized via a single subunit to CNBr-activated Sepharose 4B and subsequently treated with guanidine hydrochloride followed by renaturation to yield a catalytically active matrix-bound subunit derivative. The importance of the intact dimeric structure in the activation of the enzyme by acetate was demonstrated. Immobilization did not appear to alter the pH optimum of the enzyme, and the kinetic parameters fot the matrix-bound derivatives were generally similar to those for the soluble enzyme, but the matrix-bound derivatives showed higher thermal stability and greater resistance to denaturation than did the soluble enzyme. The rates of reaction of thiol groups of the matrix-bound derivatives with iodoacetamide in the absence and in the presence of combinations of substrates were similar to those of the soluble enzyme. Studies with 5,5'-dithiobis-(2-nitrobenzoic acid) and with iodoacetamide revealed the presence of an additional reactive thiol group in the matrix-bound subunit derivative, which is presumably masked in the dimeric derivatives.", "contents": "Properties of matrix-bound dimer and monomer derivatives of immobilized creatine kinase from rabbit skeletal muscle. Dimeric creatine kinase (EC 2.7.3.2) from rabbit skeletal muscle can be immobilized via a single subunit to CNBr-activated Sepharose 4B and subsequently treated with guanidine hydrochloride followed by renaturation to yield a catalytically active matrix-bound subunit derivative. The importance of the intact dimeric structure in the activation of the enzyme by acetate was demonstrated. Immobilization did not appear to alter the pH optimum of the enzyme, and the kinetic parameters fot the matrix-bound derivatives were generally similar to those for the soluble enzyme, but the matrix-bound derivatives showed higher thermal stability and greater resistance to denaturation than did the soluble enzyme. The rates of reaction of thiol groups of the matrix-bound derivatives with iodoacetamide in the absence and in the presence of combinations of substrates were similar to those of the soluble enzyme. Studies with 5,5'-dithiobis-(2-nitrobenzoic acid) and with iodoacetamide revealed the presence of an additional reactive thiol group in the matrix-bound subunit derivative, which is presumably masked in the dimeric derivatives."}
{"id": "PMID:28738", "title": "Purification and immunochemical characterization of malate synthase from Euglena gracilis.", "content": "Malate synthase (EC 4.1.3.2) from dark-grown Euglena gracilis was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis. The enzyme was released from acetate-grown cells by treatment with ultrasonic waves and purified from broken-cell suspensions by high-speed centrifugation and (NH4)2SO4 fractionation, followed by gel-filtration on Sepharose 6B. The final enzyme preparation was purified 190-fold compared with the crude extract. The mol.wt. of the enzyme was about 350000 as determined by gel filtration on Sepharose 6B. Treatment with sodium dodecyl sulphate and urea dissociated the enzyme into subunits of mol.wt. 175000. The pH optimum for the enzyme was 8.0 and the Km values for glyoxylate and acetyl-CoA were 50 and 80 micron respectively. Antibodies raised to the purified enzyme were shown to be monospecific by radiochemical immunoassay. Euglena anti-(malate synthase) tested on Ouchterlony double-diffusion gels gave a sharp precipitation band against acetate-grown Escherichia coli, but no immunological correspondence was observed with acetate-grown Chlorella fusca, Zea mays (maize) scutella or purified malate synthase from Ricinus communis.", "contents": "Purification and immunochemical characterization of malate synthase from Euglena gracilis. Malate synthase (EC 4.1.3.2) from dark-grown Euglena gracilis was purified to homogeneity by the criterion of polyacrylamide-gel electrophoresis. The enzyme was released from acetate-grown cells by treatment with ultrasonic waves and purified from broken-cell suspensions by high-speed centrifugation and (NH4)2SO4 fractionation, followed by gel-filtration on Sepharose 6B. The final enzyme preparation was purified 190-fold compared with the crude extract. The mol.wt. of the enzyme was about 350000 as determined by gel filtration on Sepharose 6B. Treatment with sodium dodecyl sulphate and urea dissociated the enzyme into subunits of mol.wt. 175000. The pH optimum for the enzyme was 8.0 and the Km values for glyoxylate and acetyl-CoA were 50 and 80 micron respectively. Antibodies raised to the purified enzyme were shown to be monospecific by radiochemical immunoassay. Euglena anti-(malate synthase) tested on Ouchterlony double-diffusion gels gave a sharp precipitation band against acetate-grown Escherichia coli, but no immunological correspondence was observed with acetate-grown Chlorella fusca, Zea mays (maize) scutella or purified malate synthase from Ricinus communis."}
{"id": "PMID:28739", "title": "Effects of prolonged administration of high molecular levan on arterial blood gases, oxygen transport and acid base balance in rabbits.", "content": "The effect of daily intraperitoneal injections of 100 mg of high molecular levan for 4-6 weeks on a number of physiological parameters was studied in rabbits. The parameters studied included whole blood pH, blood gases and acid-base balance. Control rabbits were similarly treated with physiological saline. In five rabbits T-50 was determined after levan treatment. None of the studied parameters was significantly affected by the levan treatment.", "contents": "Effects of prolonged administration of high molecular levan on arterial blood gases, oxygen transport and acid base balance in rabbits. The effect of daily intraperitoneal injections of 100 mg of high molecular levan for 4-6 weeks on a number of physiological parameters was studied in rabbits. The parameters studied included whole blood pH, blood gases and acid-base balance. Control rabbits were similarly treated with physiological saline. In five rabbits T-50 was determined after levan treatment. None of the studied parameters was significantly affected by the levan treatment."}
{"id": "PMID:28740", "title": "[Correlation of vasospasm and intracranial metabolism under experimental subarachnoid hemorrhage--Part 1. In reference with the acid-base-balance of cerebral blood and cerebrospinal fluid].", "content": "Cerebral vasospasm, cerebral metabolism and the acid-base-balance of blood and cerebrospinal fluid of dogs were studied during  and after the experimental subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by infusion of fresh blood into the basal cistern through a small sraniectomy in the base of the skull. Eighty adult mongrel dogs were used. Of these a complete recording was obtained in 32 cases under the constant controlled ventilation. The samples of the blood and cerebrospinal fluid (CSF) were obtained repeatedly at the inserted 1 to 3 hours from the Polyethylene tube inserted into the cisterna magna subarachnoid space, carotid artery and internal jugular vein. During these procedures, the luminal size of the intracranial basal artery was measured angiographically. Vasoconstriction of the cerebral arteries in response to experimental subarachnoid hemorrhage had a biphasic course, an acute phase (the vasoconstrictive phenomenon which lasts less than 6 hours) and chronic phase (the revasoconstriction occured and continued more than 24 hours after the hemorrhage). The former was named \"Released Group\" which consists of 16 dogs and the later was named \"Prolonged Group\" which consists of 20 dogs. In both group, pH and bicarbonate ion concentration of CSF were found to be reduced by twenty percent of the normal value on the aveaage about three hours after subarachnoid hemorrage, apparently reflecting occurence of early cerebral vasospasm. Remarkable metabolic acidosis was seen in CSF of the prolonged group as compared with in cerebral blood. The occurrence of A-V shunt was suggested in the cerebral circulation from the blood gas findings. The experimental results indicates that prolonged cerebral vasospams phenomenon causes persistent hypoxic state in the cerebral tissue. However, cellular metabolism of cerebral tissue will be probably maintained by oxygen supply necessary to cellular respiration through the blood-brain barrier from the cerebrospinal fluid.", "contents": "[Correlation of vasospasm and intracranial metabolism under experimental subarachnoid hemorrhage--Part 1. In reference with the acid-base-balance of cerebral blood and cerebrospinal fluid]. Cerebral vasospasm, cerebral metabolism and the acid-base-balance of blood and cerebrospinal fluid of dogs were studied during  and after the experimental subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by infusion of fresh blood into the basal cistern through a small sraniectomy in the base of the skull. Eighty adult mongrel dogs were used. Of these a complete recording was obtained in 32 cases under the constant controlled ventilation. The samples of the blood and cerebrospinal fluid (CSF) were obtained repeatedly at the inserted 1 to 3 hours from the Polyethylene tube inserted into the cisterna magna subarachnoid space, carotid artery and internal jugular vein. During these procedures, the luminal size of the intracranial basal artery was measured angiographically. Vasoconstriction of the cerebral arteries in response to experimental subarachnoid hemorrhage had a biphasic course, an acute phase (the vasoconstrictive phenomenon which lasts less than 6 hours) and chronic phase (the revasoconstriction occured and continued more than 24 hours after the hemorrhage). The former was named \"Released Group\" which consists of 16 dogs and the later was named \"Prolonged Group\" which consists of 20 dogs. In both group, pH and bicarbonate ion concentration of CSF were found to be reduced by twenty percent of the normal value on the aveaage about three hours after subarachnoid hemorrage, apparently reflecting occurence of early cerebral vasospasm. Remarkable metabolic acidosis was seen in CSF of the prolonged group as compared with in cerebral blood. The occurrence of A-V shunt was suggested in the cerebral circulation from the blood gas findings. The experimental results indicates that prolonged cerebral vasospams phenomenon causes persistent hypoxic state in the cerebral tissue. However, cellular metabolism of cerebral tissue will be probably maintained by oxygen supply necessary to cellular respiration through the blood-brain barrier from the cerebrospinal fluid."}
{"id": "PMID:28745", "title": "Characterization of the reaction of methyl acetimidate with sperm whale myoglobin.", "content": "The effects of pH, acetimidate concentration, temperature, and reaction time of methyl acetimidate with sperm whale myoglobulin have been assessed. Reaction at pH 9.8 and 15 degrees C for 30 min with a sixfold excess of methyl acetimidate relative to each amino group yielded six acetimidomyoglobin derivatives which were separated and purified. Reaction with tetrahydrophthalic anhydride revealed the number of amino groups that remained unreacted in each separated component and made possible further subractionation. Modification at the NH2 terminus was quantitated by automated stepwise Edman degradation. The acetimidyl and tetrahydrophthalyl groups, were readily removable. The potentiometric titration of three of the completely deprotected components showed identity with the parent untreated sperm whale myoglobin. The first of two major products was acetimidated at all 19 epsilon-amino groups but not at the NH2 terminus. The second major product bore a blocked NH2 terminus but retained one unmodified epsilon-amino group, identified after modification by trinitrobenzenesulfonate as lysine residue 77. Of the minor components, one was identified as completely acetimidated at all 20 amino groups. The other three minor components appeared to contain irreversible by-products.", "contents": "Characterization of the reaction of methyl acetimidate with sperm whale myoglobin. The effects of pH, acetimidate concentration, temperature, and reaction time of methyl acetimidate with sperm whale myoglobulin have been assessed. Reaction at pH 9.8 and 15 degrees C for 30 min with a sixfold excess of methyl acetimidate relative to each amino group yielded six acetimidomyoglobin derivatives which were separated and purified. Reaction with tetrahydrophthalic anhydride revealed the number of amino groups that remained unreacted in each separated component and made possible further subractionation. Modification at the NH2 terminus was quantitated by automated stepwise Edman degradation. The acetimidyl and tetrahydrophthalyl groups, were readily removable. The potentiometric titration of three of the completely deprotected components showed identity with the parent untreated sperm whale myoglobin. The first of two major products was acetimidated at all 19 epsilon-amino groups but not at the NH2 terminus. The second major product bore a blocked NH2 terminus but retained one unmodified epsilon-amino group, identified after modification by trinitrobenzenesulfonate as lysine residue 77. Of the minor components, one was identified as completely acetimidated at all 20 amino groups. The other three minor components appeared to contain irreversible by-products."}
{"id": "PMID:28746", "title": "Properties of D-amino acid oxidase covalently modified upon its oxidation of D-propargylglycine.", "content": "Upon oxidation of D-propargylglycine by D-amino acid oxidase, the enzyme is converted by covalent alkylation to catalytic species with different properties from those of native enzyme. At least five distinct modified enzyme species are present in the preparation, as determined by gel electro-focusing. Individual characterization of the components has not yet been attempted. The combined kinetic and spectral properties of the preparation have been studied. The modified enzymes have a marked preference for hydrophobic amino acids: the rates of oxidation decrease in the series D-phenylalanine, D-methionine, D-norleucine, D-norvaline, D-alpha-aminobutyrate, D-alanine. In addition, the observed Kms of the amino acids are increased, especially those of the smaller substrates (D-alanine and D-alpha-aminobutyrate). A primary kinetic isotope effect is observed upon oxidation of amino acids by the modified enzymes, evidence that this catalysis exhibits a different rate-determining step from catalysis by native enzyme. The modified apoenzyme exhibits intense absorbance at 318--320 nm, not present in native enzyme. This chromophore can be partially (75%) removed by treatment of the modified enzyme with hydrazine. However, the activity of native enzyme is not substantially restored by this process, suggesting the existence of superficial alkylations in addition to the modification responsible for the observed changes in kinetic parameters.", "contents": "Properties of D-amino acid oxidase covalently modified upon its oxidation of D-propargylglycine. Upon oxidation of D-propargylglycine by D-amino acid oxidase, the enzyme is converted by covalent alkylation to catalytic species with different properties from those of native enzyme. At least five distinct modified enzyme species are present in the preparation, as determined by gel electro-focusing. Individual characterization of the components has not yet been attempted. The combined kinetic and spectral properties of the preparation have been studied. The modified enzymes have a marked preference for hydrophobic amino acids: the rates of oxidation decrease in the series D-phenylalanine, D-methionine, D-norleucine, D-norvaline, D-alpha-aminobutyrate, D-alanine. In addition, the observed Kms of the amino acids are increased, especially those of the smaller substrates (D-alanine and D-alpha-aminobutyrate). A primary kinetic isotope effect is observed upon oxidation of amino acids by the modified enzymes, evidence that this catalysis exhibits a different rate-determining step from catalysis by native enzyme. The modified apoenzyme exhibits intense absorbance at 318--320 nm, not present in native enzyme. This chromophore can be partially (75%) removed by treatment of the modified enzyme with hydrazine. However, the activity of native enzyme is not substantially restored by this process, suggesting the existence of superficial alkylations in addition to the modification responsible for the observed changes in kinetic parameters."}
{"id": "PMID:28748", "title": "Quantitation of hydrogen ion and potential gradients in gastric plasma membrane vesicles.", "content": "The ATP-dependent uptake of H+ by hog gastric parietal cell vesicles was quantitated by using the pH indicator dyes bromcresol green and malachite green, the weak bases, aminopyrine and 9-aminoacridine, and the pH electrode. A K+-dependent H+ uptake was found, with a significant difference between the quantity of H+ disappearing from the medium (deltaHo) and the quantity appearing inside the vesicle (deltaHi). 9-Aminoacridine gave a lower value for the deltaHi than any of the other probes. Probes of potential such as diethyloxadicarbocyanine or oxonol dyes showed that only secondary diffusion potentials occurred during H+ uptake and that the cationic dyes in the presence of protonophores could also be used to quantitate H+ uptake. The potential in the presence of protonophore indicated a deltaHi greater than that found with the other probes. Binding sites for acridine orange were generated either by ATP or an artificial pH gradient and corresponded to the deltaHi indicated by aminopyrine. SCN- (30mM) only partially inhibited the H+ gradient, and this, coupled with the failure to detect the physiological deltapH of 6.6, indicated that these vesicles may be an incomplete model of gastric acid secretion.", "contents": "Quantitation of hydrogen ion and potential gradients in gastric plasma membrane vesicles. The ATP-dependent uptake of H+ by hog gastric parietal cell vesicles was quantitated by using the pH indicator dyes bromcresol green and malachite green, the weak bases, aminopyrine and 9-aminoacridine, and the pH electrode. A K+-dependent H+ uptake was found, with a significant difference between the quantity of H+ disappearing from the medium (deltaHo) and the quantity appearing inside the vesicle (deltaHi). 9-Aminoacridine gave a lower value for the deltaHi than any of the other probes. Probes of potential such as diethyloxadicarbocyanine or oxonol dyes showed that only secondary diffusion potentials occurred during H+ uptake and that the cationic dyes in the presence of protonophores could also be used to quantitate H+ uptake. The potential in the presence of protonophore indicated a deltaHi greater than that found with the other probes. Binding sites for acridine orange were generated either by ATP or an artificial pH gradient and corresponded to the deltaHi indicated by aminopyrine. SCN- (30mM) only partially inhibited the H+ gradient, and this, coupled with the failure to detect the physiological deltapH of 6.6, indicated that these vesicles may be an incomplete model of gastric acid secretion."}
{"id": "PMID:28750", "title": "Threonine inhibition of the aspartokinase--homoserine dehydrogenase I of Escherichia coli. Threonine binding studies.", "content": "Both activities of the aspartokinase--homoserine I (AK-HSD) of Escherichia coli are inhibited by threonine. Careful threonine binding studies have now been done which have allowed us to distinguish the various effects of threonine on the enzyme. The ultrafiltration technique of H. Paulus ((1969) Anal. Biochem. 32, 101) for measuring ligand binding was shown to be comparable with equilibrium dialysis techniques. Reduction in error by utilization of this procedure enabled us to obtain evidence for two different sets of threonine sites by direct binding studies. The binding data were mathematically consistent with two independent classes of threonine sites, each of which contained four sites per tetramer and had a Hill coefficient of about 2.3--2.5. KD for the second set of sites was five- to tenfold greater than the high affinity sites, depending upon conditions. The data now suggest that the sequential model for site--site interactions adequately describes the cooperativity of threonine binding to the high affinity set of sites.", "contents": "Threonine inhibition of the aspartokinase--homoserine dehydrogenase I of Escherichia coli. Threonine binding studies. Both activities of the aspartokinase--homoserine I (AK-HSD) of Escherichia coli are inhibited by threonine. Careful threonine binding studies have now been done which have allowed us to distinguish the various effects of threonine on the enzyme. The ultrafiltration technique of H. Paulus ((1969) Anal. Biochem. 32, 101) for measuring ligand binding was shown to be comparable with equilibrium dialysis techniques. Reduction in error by utilization of this procedure enabled us to obtain evidence for two different sets of threonine sites by direct binding studies. The binding data were mathematically consistent with two independent classes of threonine sites, each of which contained four sites per tetramer and had a Hill coefficient of about 2.3--2.5. KD for the second set of sites was five- to tenfold greater than the high affinity sites, depending upon conditions. The data now suggest that the sequential model for site--site interactions adequately describes the cooperativity of threonine binding to the high affinity set of sites."}
{"id": "PMID:28755", "title": "Sidedness of inhibition of energy transduction in oxidative phosphorylation in rat liver mitochondria by ethidium bromide.", "content": "Ethidium bromide, a new type of inhibitor of energy transduction in oxidative phosphorylation, inhibited ATP synthesis in intact mitochondria but not in submitochondrial particles, the latter being inside-out relative to the membranes of intact mitochondria. Ethidium bromide incorporated inside the submitochondrial particles inhibited ATP synthesis in the particles. The decrease of the membrane potential by valinomycin (plus KCl) inhibited only slightly the energy-dependent binding of ethidium bromide to the mitochondria. The present results show clearly that ethidium bromide inhibited energy transduction in oxidative phosphorylation by acting on the outer side (C-side) of the inner mitochondrial membrane, perhaps by neutralizing negative charges created on the surface of the C-side, and that it had no inhibitory activity on the inner side (M-side) of the membrane. Th present results show also that the energy-dependent binding of ethidium is not due to electrophoretic transport down the membrane potential; ethidium may bind to negative charges on the surface of the C-side. The present study suggest that an anisotropic distribution of electric charge in the inner mitochondrial membrane is an intermediary high energy state of oxidatvie phosphorylation.", "contents": "Sidedness of inhibition of energy transduction in oxidative phosphorylation in rat liver mitochondria by ethidium bromide. Ethidium bromide, a new type of inhibitor of energy transduction in oxidative phosphorylation, inhibited ATP synthesis in intact mitochondria but not in submitochondrial particles, the latter being inside-out relative to the membranes of intact mitochondria. Ethidium bromide incorporated inside the submitochondrial particles inhibited ATP synthesis in the particles. The decrease of the membrane potential by valinomycin (plus KCl) inhibited only slightly the energy-dependent binding of ethidium bromide to the mitochondria. The present results show clearly that ethidium bromide inhibited energy transduction in oxidative phosphorylation by acting on the outer side (C-side) of the inner mitochondrial membrane, perhaps by neutralizing negative charges created on the surface of the C-side, and that it had no inhibitory activity on the inner side (M-side) of the membrane. Th present results show also that the energy-dependent binding of ethidium is not due to electrophoretic transport down the membrane potential; ethidium may bind to negative charges on the surface of the C-side. The present study suggest that an anisotropic distribution of electric charge in the inner mitochondrial membrane is an intermediary high energy state of oxidatvie phosphorylation."}
{"id": "PMID:28756", "title": "Mechanism of generation and regulation of photopotential by bacteriorhodopsin in bimolecular lipid membrane.", "content": "Photoelectric properties of bacteriorhodopsin incorporated into a bimolecular lipid membrane were investigated with special regard to the mechanism of photoelectric field generation. It was shown that besides its proton pump and electric generator functions bacteriorhodopsin works as a possible molecular regulator of the light-induced membrane potential. When a bimolecular lipid membrane containing bacteriorhodopsin is continuously illuminated in its main visible absorption band, and afterwards by superimposed blue light matching the absorption band of the long-living photobleached bacteriorhodopsin (M412) as well, the latter either enhances or decreases the steady-state photoresponse, depending upon the intensity of the green light. Thus, the additional blue-light illumination tends to cause the resultant photoelectric membrane potential to become stabilized. Two alternative schemes are tentatively proposed for the photochemical cycle of bacteriorhodopsin whereby blue light can control photovoltage generation. A kinetic model of the proton pump and the regulation of the photoelectric membrane potential is presented. This model fits all the experimental findings, even quantitatively. From the model some kinetic and physical parameters of this light-driven pump could be determined.", "contents": "Mechanism of generation and regulation of photopotential by bacteriorhodopsin in bimolecular lipid membrane. Photoelectric properties of bacteriorhodopsin incorporated into a bimolecular lipid membrane were investigated with special regard to the mechanism of photoelectric field generation. It was shown that besides its proton pump and electric generator functions bacteriorhodopsin works as a possible molecular regulator of the light-induced membrane potential. When a bimolecular lipid membrane containing bacteriorhodopsin is continuously illuminated in its main visible absorption band, and afterwards by superimposed blue light matching the absorption band of the long-living photobleached bacteriorhodopsin (M412) as well, the latter either enhances or decreases the steady-state photoresponse, depending upon the intensity of the green light. Thus, the additional blue-light illumination tends to cause the resultant photoelectric membrane potential to become stabilized. Two alternative schemes are tentatively proposed for the photochemical cycle of bacteriorhodopsin whereby blue light can control photovoltage generation. A kinetic model of the proton pump and the regulation of the photoelectric membrane potential is presented. This model fits all the experimental findings, even quantitatively. From the model some kinetic and physical parameters of this light-driven pump could be determined."}
{"id": "PMID:28757", "title": "Two distinct rhodopsin molecules within the disc membrane of vertebrate rod outer segments.", "content": "The kinetics of the metarhodopsin I-II reaction have been measured over a wide range of temperatures (1-37C ) and pH values (4.5-8) with suspensions containing fragments of bovine rod outer segments. It was found that for all conditions the occurrence of metarhodopsin II could be described by two independent first-order processes. The fast component: slow component amplitude ratio depends upon pH and temperature. The kinetics of the lumi-metarhodopsin I reaction show the same pH dependence for the fast component: slow component amplitude ratio as the one observed for the metarhodopsin II signals. All the results observed could be described with the assumption that rhodopsin itself exists in two conformational states before bleaching which are in a pH and temperature-dependent equilibrium. This hypothesis is confirmed by its ability to explain some apparently anomalous observations in the literature.", "contents": "Two distinct rhodopsin molecules within the disc membrane of vertebrate rod outer segments. The kinetics of the metarhodopsin I-II reaction have been measured over a wide range of temperatures (1-37C ) and pH values (4.5-8) with suspensions containing fragments of bovine rod outer segments. It was found that for all conditions the occurrence of metarhodopsin II could be described by two independent first-order processes. The fast component: slow component amplitude ratio depends upon pH and temperature. The kinetics of the lumi-metarhodopsin I reaction show the same pH dependence for the fast component: slow component amplitude ratio as the one observed for the metarhodopsin II signals. All the results observed could be described with the assumption that rhodopsin itself exists in two conformational states before bleaching which are in a pH and temperature-dependent equilibrium. This hypothesis is confirmed by its ability to explain some apparently anomalous observations in the literature."}
{"id": "PMID:28758", "title": "Inside-out membrane vesicles isolated from spinach thylakoids.", "content": "Inside-out thylakoid vesicles have been separated from right-side-out material after press disruption of chloroplast lamellae. The sepration was obtained by partitionin an aqueous dextran-polyethylene glycol two-phase system, a method which utilizes differences in surface properties for separation of membrane particles. The isolated thylakoid vesicles showed the following inside-out properties: (1) light-induced reversible proton extrusion into the surrounding medium when supplied with the Photosystem II electron acceptor phenyl-p-benzoquinone; (2) a pH rise in the internal phase accompanying the external proton release, (3) sensitivity to trypsin treatment different from that of thylakoid membranes of normal orientation; (4) concave EF and convex PF freeze-fracture faces.", "contents": "Inside-out membrane vesicles isolated from spinach thylakoids. Inside-out thylakoid vesicles have been separated from right-side-out material after press disruption of chloroplast lamellae. The sepration was obtained by partitionin an aqueous dextran-polyethylene glycol two-phase system, a method which utilizes differences in surface properties for separation of membrane particles. The isolated thylakoid vesicles showed the following inside-out properties: (1) light-induced reversible proton extrusion into the surrounding medium when supplied with the Photosystem II electron acceptor phenyl-p-benzoquinone; (2) a pH rise in the internal phase accompanying the external proton release, (3) sensitivity to trypsin treatment different from that of thylakoid membranes of normal orientation; (4) concave EF and convex PF freeze-fracture faces."}
{"id": "PMID:28759", "title": "Effect of chemical modification of amino groups by fluorescamine on partial reactions of photosynthesis.", "content": "4-Phenylspiro [furan-2(3H),1-phtalan]3,3'-dione (fluorescamine) was used to covalently modify amino groups of thylakoids. Subsequently its effect on parameters of energy transfer and phosphorylating activity was assessed. While electron transport, the extent of proton uptake, 515 nm change and 9-aminoacridine quench were relatively resistant to such treatment, the functions connected to coupling factor 1, namely ATP formation by acid/base transition, ATPase activity and photophosphorylation were  affected much earlier. Photophosphorylation appears to be the most sensitive. The data are interpreted as indicating an involvement of free amino groups in energy transfer.", "contents": "Effect of chemical modification of amino groups by fluorescamine on partial reactions of photosynthesis. 4-Phenylspiro [furan-2(3H),1-phtalan]3,3'-dione (fluorescamine) was used to covalently modify amino groups of thylakoids. Subsequently its effect on parameters of energy transfer and phosphorylating activity was assessed. While electron transport, the extent of proton uptake, 515 nm change and 9-aminoacridine quench were relatively resistant to such treatment, the functions connected to coupling factor 1, namely ATP formation by acid/base transition, ATPase activity and photophosphorylation were  affected much earlier. Photophosphorylation appears to be the most sensitive. The data are interpreted as indicating an involvement of free amino groups in energy transfer."}
{"id": "PMID:28760", "title": "Redox potentials of the photosynthetic bacterial cytochromes c2 and the structural bases for variability.", "content": "The cytochromes c2 of the Rhodospirillaceae show a much greater variation in redox potential and its pH dependence than the mitochondrial cytochromes c that have been studied. It is proposed that the range of redox potential for cytochromes c2 functioning as the immediate electron donor to photo-oxidised bacteriochlorophyll may be 345-395 mV at pH 5. Closely related cytochromes c2 with different redox potentials show patterns of amino acid substitution which are consistent with changes in hydrophobicity near the haem being at least a partial determinant of redox potential. More distantly related cytochromes are difficult to compare because of the large number of amino acid substitutions and the probability that there are subtle changes in overall peptide chain folding. The redox potential versus pH curves can be analysed in terms of either one ionisation in the oxidised form or two in the oxidised form and one in the reduced. The pK in the oxidised form at higher pH values can be correlated with the pK for the disappearance or shift of the near infrared absorption band located near 695 nm. The structural bases of these ionisations are not known but the possible involvement of the haem propionate residues is discussed.", "contents": "Redox potentials of the photosynthetic bacterial cytochromes c2 and the structural bases for variability. The cytochromes c2 of the Rhodospirillaceae show a much greater variation in redox potential and its pH dependence than the mitochondrial cytochromes c that have been studied. It is proposed that the range of redox potential for cytochromes c2 functioning as the immediate electron donor to photo-oxidised bacteriochlorophyll may be 345-395 mV at pH 5. Closely related cytochromes c2 with different redox potentials show patterns of amino acid substitution which are consistent with changes in hydrophobicity near the haem being at least a partial determinant of redox potential. More distantly related cytochromes are difficult to compare because of the large number of amino acid substitutions and the probability that there are subtle changes in overall peptide chain folding. The redox potential versus pH curves can be analysed in terms of either one ionisation in the oxidised form or two in the oxidised form and one in the reduced. The pK in the oxidised form at higher pH values can be correlated with the pK for the disappearance or shift of the near infrared absorption band located near 695 nm. The structural bases of these ionisations are not known but the possible involvement of the haem propionate residues is discussed."}
{"id": "PMID:28761", "title": "The influence of pH on the conductance of lipid bimolecular membranes in relation to the alkaline ion transport induced by carboxylic carriers grisorixin, alborixin and monensin.", "content": "The influence of the pH on the stability and stoichiometry of the complexes formed by carboxylic-antibiotics such as grisorixin, alborixin and monensin with alkaline and alkaline earth cations has been investigated. The maximum values of bimolecular lipid membrane conductance are obtained with grisorixin and potassium ion. The conductance-pH curves show a very pronounced maximum in the neutral pH range. The results are analysed on the basis of a dimeric form of the ionophore in the complex and the possibility of having several charged complexes resulting from an heterogeneous reaction, the number of each complexed form depending on the pH of the bulk solutions.", "contents": "The influence of pH on the conductance of lipid bimolecular membranes in relation to the alkaline ion transport induced by carboxylic carriers grisorixin, alborixin and monensin. The influence of the pH on the stability and stoichiometry of the complexes formed by carboxylic-antibiotics such as grisorixin, alborixin and monensin with alkaline and alkaline earth cations has been investigated. The maximum values of bimolecular lipid membrane conductance are obtained with grisorixin and potassium ion. The conductance-pH curves show a very pronounced maximum in the neutral pH range. The results are analysed on the basis of a dimeric form of the ionophore in the complex and the possibility of having several charged complexes resulting from an heterogeneous reaction, the number of each complexed form depending on the pH of the bulk solutions."}
{"id": "PMID:28763", "title": "Purification and properties of an induced beta-D-glucosidase from stachybotrys atra.", "content": "We have purified an induced beta-D-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) from Stachybotrys atra to apparent homogeneity. The induced enzyme was clearly different from the constitutive beta-D-glucosidase. The molecular weight was 65 500-69 000, the pH optimum was at 6.7 and the isoelectric point at 4.8. Carbohydrate content (related to glucose) was 14.4%. The enzyme showed beta-D-glucosidase, beta-D-xylosidase and beta-D-thioglucosidase activity. These three activities sppear to be due to the same enzyme. The enzyme was strongly inhibited by D-glucono-(1 leads to 5)-lactone and nojirimycin and was very sensitive to sulfhydryl reagents.", "contents": "Purification and properties of an induced beta-D-glucosidase from stachybotrys atra. We have purified an induced beta-D-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) from Stachybotrys atra to apparent homogeneity. The induced enzyme was clearly different from the constitutive beta-D-glucosidase. The molecular weight was 65 500-69 000, the pH optimum was at 6.7 and the isoelectric point at 4.8. Carbohydrate content (related to glucose) was 14.4%. The enzyme showed beta-D-glucosidase, beta-D-xylosidase and beta-D-thioglucosidase activity. These three activities sppear to be due to the same enzyme. The enzyme was strongly inhibited by D-glucono-(1 leads to 5)-lactone and nojirimycin and was very sensitive to sulfhydryl reagents."}
{"id": "PMID:28765", "title": "The two human trypsinogens: catalytic properties of the corresponding trypsins.", "content": "The catalytic properties of the two human trypsins obtained from purified trypsinogens have been studied. The catalytic rate constant kcat and the pK of the ionisable residue implicated in the active site have been determined with Bz-Arg-OEt. The hydrolysis of Tos-Arg-OMe by human trypsins does not follow the simple Michaelis-Menten scheme and indicates a difference in the conformational flexibility of the active site-regions of the two enzymes. Both enzyme are readily autolyzed and calcium ion plays a fundamental role in stabilizing trypsin activity. However trypsin 2 self-digests more rapidly than trypsin 1. These results are a prerequisite to the elucidation of the fate of pancreatic enzymes in human digestive tract.", "contents": "The two human trypsinogens: catalytic properties of the corresponding trypsins. The catalytic properties of the two human trypsins obtained from purified trypsinogens have been studied. The catalytic rate constant kcat and the pK of the ionisable residue implicated in the active site have been determined with Bz-Arg-OEt. The hydrolysis of Tos-Arg-OMe by human trypsins does not follow the simple Michaelis-Menten scheme and indicates a difference in the conformational flexibility of the active site-regions of the two enzymes. Both enzyme are readily autolyzed and calcium ion plays a fundamental role in stabilizing trypsin activity. However trypsin 2 self-digests more rapidly than trypsin 1. These results are a prerequisite to the elucidation of the fate of pancreatic enzymes in human digestive tract."}
{"id": "PMID:28766", "title": "Purification and characterization of a myosin-cleaving protease from rat heart myofibrils.", "content": "A proteolytic enzyme, which causes the limited degradation of cardiac myosin, was purified from rat heart myofibrils. The purified enzyme (a myosin-cleaving protease) was apparently homogeneous by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. Autolysis of the purified enzyme was observed at neutral pH without high concentration of CaCl2. The molecular weight was estimated to be 26 000-27 000. The enzyme was active against casein, N-acetyl-L-tyrosine ethyl ester and N-glutaryl-L-phenylalanine-4-nitroanilide (Glu-Phe-NAn), but less active with N-benzoyl-DL-arginine-4-nitroanilide. Optimum pH values for the enzyme were 9.0 for casein and 8.4 for Glu-Phe-NAn. Caseinolytic activity of the enzyme was completely inhibited with phenylmethylsulfonyl fluoride and diisopropylphosphofluoride and partially inhibited with L-1-tosyl-L-phenylalanine chloromethyl ketone (Tos-PheCH2Cl) and soybean trypsin inhibitor. Tos-LysCH2Cl had no effect. Sulfhydryl reagents, metal-chelating agents and metal ions except for Zn2+ had little or no effect on the activity. Degradation of cardiac myosin with the enzyme produced two fragments having molecular weights of 130 000 and 94 000, accompanied by the disappearance of myosin heavy chain and light chain 2. Myosin degradation with the enzyme was more restrictive than with chymotrypsin.", "contents": "Purification and characterization of a myosin-cleaving protease from rat heart myofibrils. A proteolytic enzyme, which causes the limited degradation of cardiac myosin, was purified from rat heart myofibrils. The purified enzyme (a myosin-cleaving protease) was apparently homogeneous by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. Autolysis of the purified enzyme was observed at neutral pH without high concentration of CaCl2. The molecular weight was estimated to be 26 000-27 000. The enzyme was active against casein, N-acetyl-L-tyrosine ethyl ester and N-glutaryl-L-phenylalanine-4-nitroanilide (Glu-Phe-NAn), but less active with N-benzoyl-DL-arginine-4-nitroanilide. Optimum pH values for the enzyme were 9.0 for casein and 8.4 for Glu-Phe-NAn. Caseinolytic activity of the enzyme was completely inhibited with phenylmethylsulfonyl fluoride and diisopropylphosphofluoride and partially inhibited with L-1-tosyl-L-phenylalanine chloromethyl ketone (Tos-PheCH2Cl) and soybean trypsin inhibitor. Tos-LysCH2Cl had no effect. Sulfhydryl reagents, metal-chelating agents and metal ions except for Zn2+ had little or no effect on the activity. Degradation of cardiac myosin with the enzyme produced two fragments having molecular weights of 130 000 and 94 000, accompanied by the disappearance of myosin heavy chain and light chain 2. Myosin degradation with the enzyme was more restrictive than with chymotrypsin."}
{"id": "PMID:28767", "title": "Purification and properties of guanylate cyclase from the synaptosomal soluble fraction of rat brain.", "content": "Guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) was purified 2250-fold from the synaptosomal soluble fraction of rat brain. The specific activity of the purified enzyme reached 41 nmol cyclic GMP formed per min per mg protein at 37 degrees C. In the purified preparation, GTPase activity was not detected and cyclic GMP phosphodiesterase activity was less than 4% of guanylate cyclase activity. The molecular weight was approx. 480 000. Lubrol PX, hydroxylamine, or NaN3 activated the guanylate cyclase in crude preparations, but had no effect on the purified enzyme. In contrast, NaN3 plus catalase, N-methyl-N'-nitro-N-nitrosoguanidine or sodium nitroprusside activated the purified enzyme. The purified enzyme required Mn2+ for its activity; the maximum activity was observed at 3-5 mM. Cyclic GMP activated guanylate cyclase activity 1.4-fold at 2 mM, whereas inorganic pyrophosphate inhibited it by about 50% at 0.2 mM. Guanylyl-(beta,gamma-methylene)-diphosphonate and guanylyl-imidodiphosphate, analogues of GTP, served as substrates of guanylate cyclase in the purified enzyme preparation. NaN3 plus catalase or N-methyl-N'-nitro-N-nitrosoguanidine also remarkably activated guanylate cyclase activity when the analogues of GTP were used as substrates.", "contents": "Purification and properties of guanylate cyclase from the synaptosomal soluble fraction of rat brain. Guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) was purified 2250-fold from the synaptosomal soluble fraction of rat brain. The specific activity of the purified enzyme reached 41 nmol cyclic GMP formed per min per mg protein at 37 degrees C. In the purified preparation, GTPase activity was not detected and cyclic GMP phosphodiesterase activity was less than 4% of guanylate cyclase activity. The molecular weight was approx. 480 000. Lubrol PX, hydroxylamine, or NaN3 activated the guanylate cyclase in crude preparations, but had no effect on the purified enzyme. In contrast, NaN3 plus catalase, N-methyl-N'-nitro-N-nitrosoguanidine or sodium nitroprusside activated the purified enzyme. The purified enzyme required Mn2+ for its activity; the maximum activity was observed at 3-5 mM. Cyclic GMP activated guanylate cyclase activity 1.4-fold at 2 mM, whereas inorganic pyrophosphate inhibited it by about 50% at 0.2 mM. Guanylyl-(beta,gamma-methylene)-diphosphonate and guanylyl-imidodiphosphate, analogues of GTP, served as substrates of guanylate cyclase in the purified enzyme preparation. NaN3 plus catalase or N-methyl-N'-nitro-N-nitrosoguanidine also remarkably activated guanylate cyclase activity when the analogues of GTP were used as substrates."}
{"id": "PMID:28768", "title": "Immobilized hybrids of glyceraldehyde-3-phosphate dehydrogenase.", "content": "Yeast glyceraldehyde-3-phosphate dehydrogenase (glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) immobilized on CNBr-activated Sepharose 4-B has been subjected to dissociation to obtain matrix-bound dimeric species of the enzyme. Hybridization was then performed using soluble glyceraldehyde-3-phosphate dehydrogenase isolated from rat skeletal muscle. Immobilized hybrid tetramers thus obtained were demonstrated to exhibit two distinct pH-optima of activity characteristic of the yeast and muscle enzymes, respectively. The results indicate that under appropriate conditions the activity of each of the dimers composing the immobilized hybrid tetramer can be studied separately.", "contents": "Immobilized hybrids of glyceraldehyde-3-phosphate dehydrogenase. Yeast glyceraldehyde-3-phosphate dehydrogenase (glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) immobilized on CNBr-activated Sepharose 4-B has been subjected to dissociation to obtain matrix-bound dimeric species of the enzyme. Hybridization was then performed using soluble glyceraldehyde-3-phosphate dehydrogenase isolated from rat skeletal muscle. Immobilized hybrid tetramers thus obtained were demonstrated to exhibit two distinct pH-optima of activity characteristic of the yeast and muscle enzymes, respectively. The results indicate that under appropriate conditions the activity of each of the dimers composing the immobilized hybrid tetramer can be studied separately."}
{"id": "PMID:28770", "title": "The kinetics of methyl viologen oxidation and reduction by the hydrogenase from Clostridium pasteurianum.", "content": "A mechanism for the reduction and oxidation of methyl viologen by Clostridium pasteurianum hydrogenase (hydrogen:ferredoxin oxidoreductase, EC 1.12.7.1) is proposed. Double reciprocal plots for methyl viologen reduction and oxidation at pH values 7.0-9.85 are linear, and the plots for reduction and oxidation are intersecting. Such data are consistent with a mechanism in which the H2 and one methyl viologen bind (either in order or randomly) with subsequent reduction and release of the methyl viologen. A second methyl viologen then is bound, reduced and released. Comparison of the calculated Keq' with the Haldane expression in which both methyl viologens react at the same rate show a large difference. This difference indicates that the two methyl viologens react at different rates. Addition of oxidized electron carriers inhibits the hydrogen-deuterium exchange reaction (i.e., the exchange of protons between H2 and 2H2O). CO reversibly inhibits methyl viologen reduction and is competitive vs. H2. O2 acts as an irreversible inhibitor.", "contents": "The kinetics of methyl viologen oxidation and reduction by the hydrogenase from Clostridium pasteurianum. A mechanism for the reduction and oxidation of methyl viologen by Clostridium pasteurianum hydrogenase (hydrogen:ferredoxin oxidoreductase, EC 1.12.7.1) is proposed. Double reciprocal plots for methyl viologen reduction and oxidation at pH values 7.0-9.85 are linear, and the plots for reduction and oxidation are intersecting. Such data are consistent with a mechanism in which the H2 and one methyl viologen bind (either in order or randomly) with subsequent reduction and release of the methyl viologen. A second methyl viologen then is bound, reduced and released. Comparison of the calculated Keq' with the Haldane expression in which both methyl viologens react at the same rate show a large difference. This difference indicates that the two methyl viologens react at different rates. Addition of oxidized electron carriers inhibits the hydrogen-deuterium exchange reaction (i.e., the exchange of protons between H2 and 2H2O). CO reversibly inhibits methyl viologen reduction and is competitive vs. H2. O2 acts as an irreversible inhibitor."}
{"id": "PMID:28771", "title": "Esterase XXVII. Purification and characterization of esterase-9A of mouse kidney.", "content": "Esterase-9A, which appears electrophoretically as a triplet of the bands III-50, III-40 and III-30, was isolated from the kidneys of male NMRI-mice by isoelectrofocusing and refocusing followed by repeated molecular sieve chromography. The overall purification was approx. 250 fold and each of the three bands was isolated separately. The band of the triplet nearest to the cathode, III-50, changed in vitro into the satellite bands III-40 and III-30 and, further, into the band III-22 not observed before in the homogenate. It is assumed that the band III-50 represents the original gene product. The molecular weight (45 000) of the band III-50 is identical with those of III-40 and III-30, as measured by analytical electrophoresis, whereas the molecular weight obtained by thin-layer chromatography was 51 000. There were no obvious signs that esterase-9 was composed of subunits. The Km constant for 4-nitrophenyl proprionate was identical for each of three bands. The esterase-9A is the first testosterone-dependent isozyme of the mouse carboxylesterase (carboxylicester hydrolase, EC 3.1.1.1) system which has been isolated.", "contents": "Esterase XXVII. Purification and characterization of esterase-9A of mouse kidney. Esterase-9A, which appears electrophoretically as a triplet of the bands III-50, III-40 and III-30, was isolated from the kidneys of male NMRI-mice by isoelectrofocusing and refocusing followed by repeated molecular sieve chromography. The overall purification was approx. 250 fold and each of the three bands was isolated separately. The band of the triplet nearest to the cathode, III-50, changed in vitro into the satellite bands III-40 and III-30 and, further, into the band III-22 not observed before in the homogenate. It is assumed that the band III-50 represents the original gene product. The molecular weight (45 000) of the band III-50 is identical with those of III-40 and III-30, as measured by analytical electrophoresis, whereas the molecular weight obtained by thin-layer chromatography was 51 000. There were no obvious signs that esterase-9 was composed of subunits. The Km constant for 4-nitrophenyl proprionate was identical for each of three bands. The esterase-9A is the first testosterone-dependent isozyme of the mouse carboxylesterase (carboxylicester hydrolase, EC 3.1.1.1) system which has been isolated."}
{"id": "PMID:28772", "title": "Characterization of sterol-ester hydrolase in Saccharomyces cerevisiae.", "content": "A homgenate of Saccharomyces cerevisiae grown under semi-anaerobic as well as aerobic conditions was found to catalyze the hydrolysis of fatty acid esters of sterols in the presence of Triton X-100. The enzyme levels in cells grown under various conditions were similar and the enzyme had a broad substrate specificity for sterol esters. The enzyme was localized in the mitochondrial fraction for the aerobically grown cells and in the mitochondrial and cytosolic fractions for the semi-anaerobically grown cells.", "contents": "Characterization of sterol-ester hydrolase in Saccharomyces cerevisiae. A homgenate of Saccharomyces cerevisiae grown under semi-anaerobic as well as aerobic conditions was found to catalyze the hydrolysis of fatty acid esters of sterols in the presence of Triton X-100. The enzyme levels in cells grown under various conditions were similar and the enzyme had a broad substrate specificity for sterol esters. The enzyme was localized in the mitochondrial fraction for the aerobically grown cells and in the mitochondrial and cytosolic fractions for the semi-anaerobically grown cells."}
{"id": "PMID:28773", "title": "Temperature and pH effects with immobilized electric eel acetylcholinesterase.", "content": "Kinetic studies were made with 2 forms of immobilized acetylcholinesterase: enzyme trapped in polyacrylamide gel which was cut into slices; and enzyme attached to the inner surface of nylon tubing. Rates were measured at substrate concentrations which were low and high with reference to the Michaelis constant, and over the temperature range 16-40 degrees C. Low activation energies (1.7-2.7 kcal mol-1) were obtained at low substrate concentrations, indicating diffusion control. At high substrate concentrations the Arrhenius plots were non-linear and the activation energies substantially higher, and there is less diffusion control. With enzyme-polyacrylamide slices, there was a continuous increase in rate with increasing pH, in contrast to the bell-shaped behavior with free enzyme. A theoretical treatment suggests that this is due to the lowering of local pH as a result of the acid released in the hydrolysis.", "contents": "Temperature and pH effects with immobilized electric eel acetylcholinesterase. Kinetic studies were made with 2 forms of immobilized acetylcholinesterase: enzyme trapped in polyacrylamide gel which was cut into slices; and enzyme attached to the inner surface of nylon tubing. Rates were measured at substrate concentrations which were low and high with reference to the Michaelis constant, and over the temperature range 16-40 degrees C. Low activation energies (1.7-2.7 kcal mol-1) were obtained at low substrate concentrations, indicating diffusion control. At high substrate concentrations the Arrhenius plots were non-linear and the activation energies substantially higher, and there is less diffusion control. With enzyme-polyacrylamide slices, there was a continuous increase in rate with increasing pH, in contrast to the bell-shaped behavior with free enzyme. A theoretical treatment suggests that this is due to the lowering of local pH as a result of the acid released in the hydrolysis."}
{"id": "PMID:28774", "title": "Enzyme behaviour and molecular environment. The effects of ionic strength, detergents, linear polyanions and phospholipids on the pH profile of soluble cytochrome oxidase.", "content": "The activity vs. pH profile for the oxidation of ferrocytochrome c by purified cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) was investigated as a function of ionic strength (from 10 to 200 mM) in the absence and in the presence of various perturbants: Tween 20, linear polyanions (RNA, heparin, polyglutamic acid) and phospholipids (asolectin, phosphatidylcholine, phosphatidic acid and cardiolipin). The activation induced by Tween 20 and \"zero net charge\" phospholipid liposomes was not pH dependent. On the other hand, linear polyanions and polyanionic liposomes strongly perturbed the pH profile, mostly at low ionic strength, by shifting the pH optimum about 1.7 pH units towards alkaline pH values. This effect was reversed by increasing ionic strength. These observations are interpreted in the light of polyelectrolyte theory. Since these results show striking with membrane-bound enzyme, it is concluded that in vivo cytochrome oxidase is located within polyanionic sites of the micochondrial membrane. The activation broght about by phospholipids may result from two posible processes: creation of a hydrophobic environment by the non-polar tails, preventing autoaggregation; and creation of a suitable polyelectrolytic environment by the polar heads (of non zero net charge), increasing the intrinsic reaction rate.", "contents": "Enzyme behaviour and molecular environment. The effects of ionic strength, detergents, linear polyanions and phospholipids on the pH profile of soluble cytochrome oxidase. The activity vs. pH profile for the oxidation of ferrocytochrome c by purified cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) was investigated as a function of ionic strength (from 10 to 200 mM) in the absence and in the presence of various perturbants: Tween 20, linear polyanions (RNA, heparin, polyglutamic acid) and phospholipids (asolectin, phosphatidylcholine, phosphatidic acid and cardiolipin). The activation induced by Tween 20 and \"zero net charge\" phospholipid liposomes was not pH dependent. On the other hand, linear polyanions and polyanionic liposomes strongly perturbed the pH profile, mostly at low ionic strength, by shifting the pH optimum about 1.7 pH units towards alkaline pH values. This effect was reversed by increasing ionic strength. These observations are interpreted in the light of polyelectrolyte theory. Since these results show striking with membrane-bound enzyme, it is concluded that in vivo cytochrome oxidase is located within polyanionic sites of the micochondrial membrane. The activation broght about by phospholipids may result from two posible processes: creation of a hydrophobic environment by the non-polar tails, preventing autoaggregation; and creation of a suitable polyelectrolytic environment by the polar heads (of non zero net charge), increasing the intrinsic reaction rate."}
{"id": "PMID:28775", "title": "Zinc stoichiometry in Escherichia coli alkaline phosphatase. Studies by 31P NMR and ion-exchange chromatography.", "content": "31P nuclear magnetic resonance spectra and enzymatic activities are compared for alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1) species with different zinc contents. The enzyme containing two Zn2+ per protein dimer exists in two forms; one, prepared by dialysis of native enzyme, has full enzymatic activity and a 31P magnetic resonance spectrum similar to but distinguishable from that of the native enzyme containing four or more Zn2+. The other form, prepared by restoring two Zn2+ to apoenzyme, has low enzymatic activity and a 31P magnetic resonance spectrum that indicates stoichiometric binding of phosphate, but otherwise altered properties. Reconstituted enzyme with four Zn2+ is similar to but distinguishable from native enzyme with four Zn2+. Chromatography on DEAE-cellulose can separate apoenzyme and enzyme containing two Zn2+ and suggests that the binding of a pair of Zn2+ is cooperative.", "contents": "Zinc stoichiometry in Escherichia coli alkaline phosphatase. Studies by 31P NMR and ion-exchange chromatography. 31P nuclear magnetic resonance spectra and enzymatic activities are compared for alkaline phosphatase (orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1) species with different zinc contents. The enzyme containing two Zn2+ per protein dimer exists in two forms; one, prepared by dialysis of native enzyme, has full enzymatic activity and a 31P magnetic resonance spectrum similar to but distinguishable from that of the native enzyme containing four or more Zn2+. The other form, prepared by restoring two Zn2+ to apoenzyme, has low enzymatic activity and a 31P magnetic resonance spectrum that indicates stoichiometric binding of phosphate, but otherwise altered properties. Reconstituted enzyme with four Zn2+ is similar to but distinguishable from native enzyme with four Zn2+. Chromatography on DEAE-cellulose can separate apoenzyme and enzyme containing two Zn2+ and suggests that the binding of a pair of Zn2+ is cooperative."}
{"id": "PMID:28776", "title": "NMR and enzymatic investigation of the interaction between elastase and sodium trifluoroacetate.", "content": "At pH 5.5, sodium trifluoroacetate is a potent competitive inhibitor of porcine elastase (Ki = 2.6 mM) and human leukocyte elastase (Ki = 9.3 mM). For both enzymes the Ki increases strongly with pH. Sodium fluoride is inactive on pancreatic elastase and sodium acetate is a weak inhibitor of this enzyme. Trifluoroethanol inhibits both enzymes but is less active than trifluoroacetate in acidic pH conditions. Bovine trypsin and alpha-chymotrypsin are resistant to the action of sodium trifluoroacetate and trifluoroethanol. The interaction between sodium trifluoroacetate and pancreatic elastase is  also demonstrated by 19F NMR spectroscopy. Trifluoroacetyltrialanine is able to displace trifluoroacetate from its complex with pancreatic elastase. In addition, a method using turkey ovomucoid for the active site titration of leukocyte and pancreatic elastase is described.", "contents": "NMR and enzymatic investigation of the interaction between elastase and sodium trifluoroacetate. At pH 5.5, sodium trifluoroacetate is a potent competitive inhibitor of porcine elastase (Ki = 2.6 mM) and human leukocyte elastase (Ki = 9.3 mM). For both enzymes the Ki increases strongly with pH. Sodium fluoride is inactive on pancreatic elastase and sodium acetate is a weak inhibitor of this enzyme. Trifluoroethanol inhibits both enzymes but is less active than trifluoroacetate in acidic pH conditions. Bovine trypsin and alpha-chymotrypsin are resistant to the action of sodium trifluoroacetate and trifluoroethanol. The interaction between sodium trifluoroacetate and pancreatic elastase is  also demonstrated by 19F NMR spectroscopy. Trifluoroacetyltrialanine is able to displace trifluoroacetate from its complex with pancreatic elastase. In addition, a method using turkey ovomucoid for the active site titration of leukocyte and pancreatic elastase is described."}
{"id": "PMID:28777", "title": "Purification and properties of pig brain guanine deaminase.", "content": "Guanine deaminase (guanine aminohydrolase, EC 3.5.4.3) from pig brain was purified to homogeneity by column chromatography and ammonium sulphate fractionation. Homogeneity was established by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulphate (SDS). The molecular weight of 110 000 was determined by gel filtration and sucrose density gradient centrifugation. SDS polyacrylamide gel electrophoresis indicated subunits of a molecular weight of 50 000. The amino acid composition, the isoelectric point and the number of -SH groups were determined. 5.5'-Dithiobis-(2-nitrobenzoic acid) reacts with about seven -SH groups in the native enzyme, but upon denaturation with SDS, 10 -SH groups react with this former reagent. Using electrolytic reduction, 44 half-cystines were determined in accordance with the number of cysteic acid residues determined by amino acid analysis after performic acid oxidation. The Km values determined for substrates of the enzyme were 1.1 . 10(-5) M for guanine in 0.1 M Tris. HCl buffer (pH 8.0) and 3.3 . 10(-4) M for 8-azaguanine in 0.1 M phosphate buffer, pH 6.4. The pKa values determined for ionizable groups of the active site of the enzyme were near pH 6.2 and pH 8.2. The chemical and kinetic evidence suggests that cysteine and histidine may be essential for the catalysis.", "contents": "Purification and properties of pig brain guanine deaminase. Guanine deaminase (guanine aminohydrolase, EC 3.5.4.3) from pig brain was purified to homogeneity by column chromatography and ammonium sulphate fractionation. Homogeneity was established by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulphate (SDS). The molecular weight of 110 000 was determined by gel filtration and sucrose density gradient centrifugation. SDS polyacrylamide gel electrophoresis indicated subunits of a molecular weight of 50 000. The amino acid composition, the isoelectric point and the number of -SH groups were determined. 5.5'-Dithiobis-(2-nitrobenzoic acid) reacts with about seven -SH groups in the native enzyme, but upon denaturation with SDS, 10 -SH groups react with this former reagent. Using electrolytic reduction, 44 half-cystines were determined in accordance with the number of cysteic acid residues determined by amino acid analysis after performic acid oxidation. The Km values determined for substrates of the enzyme were 1.1 . 10(-5) M for guanine in 0.1 M Tris. HCl buffer (pH 8.0) and 3.3 . 10(-4) M for 8-azaguanine in 0.1 M phosphate buffer, pH 6.4. The pKa values determined for ionizable groups of the active site of the enzyme were near pH 6.2 and pH 8.2. The chemical and kinetic evidence suggests that cysteine and histidine may be essential for the catalysis."}
{"id": "PMID:28778", "title": "[Purification and detection of multiple forms of histidine decarboxylase in rat gastric mucosa (author's transl)].", "content": "A specific histidine decarboxylase from rat gastric mucosa has been obtained at high purity and good yield (purification about 600-fold). The purification procedure included double (NH4)2SO4 fractionation, ion-exchange chromatography, preparative isoelectric focusing in a granulated gel and gel filtration. Only the specific histidine enzyme was obtained by that procedure; DOPA decarboxylase, a non-specific enzyme, was absent in our final preparation. Each step of the purification was visualized by polyacrylamide gel electrophoresis and analytical isoelectric focusing. The purified enzyme was apparently homogenous by criteria of electrophoresis and gel filtration and has a molecular weight of 94 000. Several protein bands appeared after isoelectric focusing and the enzyme activity was localized in 3 distinct peaks. The gastric enzyme consists of 3 active forms which could be distinguished by their isoelectric points: 5.4, 5.75 and 6. Moleculare weights estimated by SDS polyacrylamide gel electrophoresis were 97 000, 93 000 and 90 000, and no subunits were observed. Pyridoxal phosphate was required as a coenzyme and resolution of the holoenzyme agreed with a portion of the coenzyme tightly bound to the apoenzyme. The purified enzyme was stable at low ionic strength, near neutral pH; concentrated reducing agents inhibit the enzyme.", "contents": "[Purification and detection of multiple forms of histidine decarboxylase in rat gastric mucosa (author's transl)]. A specific histidine decarboxylase from rat gastric mucosa has been obtained at high purity and good yield (purification about 600-fold). The purification procedure included double (NH4)2SO4 fractionation, ion-exchange chromatography, preparative isoelectric focusing in a granulated gel and gel filtration. Only the specific histidine enzyme was obtained by that procedure; DOPA decarboxylase, a non-specific enzyme, was absent in our final preparation. Each step of the purification was visualized by polyacrylamide gel electrophoresis and analytical isoelectric focusing. The purified enzyme was apparently homogenous by criteria of electrophoresis and gel filtration and has a molecular weight of 94 000. Several protein bands appeared after isoelectric focusing and the enzyme activity was localized in 3 distinct peaks. The gastric enzyme consists of 3 active forms which could be distinguished by their isoelectric points: 5.4, 5.75 and 6. Moleculare weights estimated by SDS polyacrylamide gel electrophoresis were 97 000, 93 000 and 90 000, and no subunits were observed. Pyridoxal phosphate was required as a coenzyme and resolution of the holoenzyme agreed with a portion of the coenzyme tightly bound to the apoenzyme. The purified enzyme was stable at low ionic strength, near neutral pH; concentrated reducing agents inhibit the enzyme."}
{"id": "PMID:28779", "title": "Hydrogen bonding of flavoprotein. I. Effect of hydrogen bonding on electronic spectra of flavoprotein.", "content": "The effect of hydrogen bonding on the transition energy and the oscillator strength of the isoalloxazine nucleus of flavins was studied by the molecular orbital method. Among the possible hydrogen bondings examined, characteristic spectral shifts were found for the hydrogen bondings at N(1) and N(5) of the nucleus. The hydrogen bonding at N(1) resulted in the shift of the first absorption band towards blue and that of the second one towards red. On the other hand, the hydrogen bonding at N(5) resulted in the shifts of both the first and the second band towards red. The spectral characteristics reported on Clostridium MP and Desulfovibrio vulgaris flavodoxin coincided with the calculated results. The application of the calculated results to D-amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating), EC 1.4.3.3) led to the conclusion that hydrogen bonding occurs at O(12), N(3)H, O(14) and N(5) of the isoalloxazine nucleus. The occurrence of hydrogen bondings at O(12), N(3)H, and O(14) is favorable for N(5) of the isoalloxazine nucleus to accept electron from an electron donor.", "contents": "Hydrogen bonding of flavoprotein. I. Effect of hydrogen bonding on electronic spectra of flavoprotein. The effect of hydrogen bonding on the transition energy and the oscillator strength of the isoalloxazine nucleus of flavins was studied by the molecular orbital method. Among the possible hydrogen bondings examined, characteristic spectral shifts were found for the hydrogen bondings at N(1) and N(5) of the nucleus. The hydrogen bonding at N(1) resulted in the shift of the first absorption band towards blue and that of the second one towards red. On the other hand, the hydrogen bonding at N(5) resulted in the shifts of both the first and the second band towards red. The spectral characteristics reported on Clostridium MP and Desulfovibrio vulgaris flavodoxin coincided with the calculated results. The application of the calculated results to D-amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating), EC 1.4.3.3) led to the conclusion that hydrogen bonding occurs at O(12), N(3)H, O(14) and N(5) of the isoalloxazine nucleus. The occurrence of hydrogen bondings at O(12), N(3)H, and O(14) is favorable for N(5) of the isoalloxazine nucleus to accept electron from an electron donor."}
{"id": "PMID:28780", "title": "Soluble NADH-cytochrome b5 reductase from rabbit liver cytosol: partial purification and characterization.", "content": "A soluble form of NADH-cytochrome b5 reductase (NADH: ferricytochrome b5 oxidoreductase, EC 1.6.2.2) was found in the cytosolic fraction of rabbit liver. The partially purified enzyme was strictly specific for NADH. It catalyzed the reduction of several substrates such as the methemoglobin-ferrocyanide complex (Hegesh, E. and Avron, M. (1967) Biochim. Biophys. Acta 146, 91-101) (apparent Km: 8 micrometer), potassium ferricyanide (apparent Km: 10 micrometer) and ferricytochrome b5 (apparent Km: 15 micrometer). Upon acrylamide gel isoelectro-focusing followed by specific staining, the enzyme was resolved into four bands (isoelectric pH: 7.05, 6.70, 6.50 and 6.30). The optimum pH of activity with ferricytochrome b5 as a substrate was 6.5. The estimated molecular weight was 25 000--30 000. The enzyme was unsensitive to cyanide. It was strongly inhibited by p-hydroxymercuribenzoate. The cytosolic liver cytochrome b5 reductase was immunologically related to the soluble cytochrome b5 reductase from human and rabbit red-cells, and to the microsomal cytochrome b5 reductase from rabbit liver.", "contents": "Soluble NADH-cytochrome b5 reductase from rabbit liver cytosol: partial purification and characterization. A soluble form of NADH-cytochrome b5 reductase (NADH: ferricytochrome b5 oxidoreductase, EC 1.6.2.2) was found in the cytosolic fraction of rabbit liver. The partially purified enzyme was strictly specific for NADH. It catalyzed the reduction of several substrates such as the methemoglobin-ferrocyanide complex (Hegesh, E. and Avron, M. (1967) Biochim. Biophys. Acta 146, 91-101) (apparent Km: 8 micrometer), potassium ferricyanide (apparent Km: 10 micrometer) and ferricytochrome b5 (apparent Km: 15 micrometer). Upon acrylamide gel isoelectro-focusing followed by specific staining, the enzyme was resolved into four bands (isoelectric pH: 7.05, 6.70, 6.50 and 6.30). The optimum pH of activity with ferricytochrome b5 as a substrate was 6.5. The estimated molecular weight was 25 000--30 000. The enzyme was unsensitive to cyanide. It was strongly inhibited by p-hydroxymercuribenzoate. The cytosolic liver cytochrome b5 reductase was immunologically related to the soluble cytochrome b5 reductase from human and rabbit red-cells, and to the microsomal cytochrome b5 reductase from rabbit liver."}
{"id": "PMID:28781", "title": "Purification and properties of rat liver mitochondrial glutathione peroxidase.", "content": "Glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) was purified from rat liver mitochondria. The enzyme was shown to be pure by polyacrylamide-gel electrophoresis and to contain multiple forms that differed in charge. Selenium was specifically associated with the enzyme. The enzyme was inhibited by iodoacetic acid and iodoacetamide in an unusual pattern of reduction by sulfhydryl compounds and pH dependency. The mitochondrial and cytoplasmic forms of the enzyme were compared, and an explanation of the inhibition patterns is offered.", "contents": "Purification and properties of rat liver mitochondrial glutathione peroxidase. Glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) was purified from rat liver mitochondria. The enzyme was shown to be pure by polyacrylamide-gel electrophoresis and to contain multiple forms that differed in charge. Selenium was specifically associated with the enzyme. The enzyme was inhibited by iodoacetic acid and iodoacetamide in an unusual pattern of reduction by sulfhydryl compounds and pH dependency. The mitochondrial and cytoplasmic forms of the enzyme were compared, and an explanation of the inhibition patterns is offered."}
{"id": "PMID:28782", "title": "N-Acetyltransferase activity of the rat Harderian gland.", "content": "Harderian gland extracts from male rats catalyze the conversion of serotonin to N-acetylserotonin and of tryptamine to N-acetyltryptamine. The reaction is linear up to 14 mg tissue and departs from linearity after 10 min. The pH otpimum with tryptamine as substrate is between 8 and 9. Enzymic activity of the gland in vivo does not show diurnal variations. Enzymic activity of tissue in organ culture is not stimulated by 10 micrometer isoproterenol or 100 micrometer dibutyryl cyclic AMP. Harderian gland tissue in culture can acetylate tryptamine and serotonin and can O-methylate the N-acetylserotonin to form melatonin.", "contents": "N-Acetyltransferase activity of the rat Harderian gland. Harderian gland extracts from male rats catalyze the conversion of serotonin to N-acetylserotonin and of tryptamine to N-acetyltryptamine. The reaction is linear up to 14 mg tissue and departs from linearity after 10 min. The pH otpimum with tryptamine as substrate is between 8 and 9. Enzymic activity of the gland in vivo does not show diurnal variations. Enzymic activity of tissue in organ culture is not stimulated by 10 micrometer isoproterenol or 100 micrometer dibutyryl cyclic AMP. Harderian gland tissue in culture can acetylate tryptamine and serotonin and can O-methylate the N-acetylserotonin to form melatonin."}
{"id": "PMID:28783", "title": "Cholesteryl ester and triglyceride hydrolysis by an acid lipase from rabbit aorta.", "content": "The properties of the triglyceride- and cholesteryl ester-hydrolyzing activity by an acid lipase from rabbit aortic tissue were compared under different experimental conditions. Radiolabeled cholesteryl oleate or triolein was incorporated into phospholipid vesicles by sonication and the resulting preparations were used for in vitro studies. No distinction was observed between triglyceride lipase and cholesterol esterase activity in the aortic cytosol fraction following either thermal inactivation, inhibition by a mercurial, fractionation by ammonium sulfate or acid precipitation, or DEAE-cellulose chromatography. Addition of rabbit lipoproteins to the assay system resulted in inhibition of both cholesterol esterase and triglyceride lipase activity. Parallel changes in the hydrolysis of both substrates also were observed when exogenously added lipids were added to the incubation system in various physical states. Specificities of the enzyme system towards different cholesteryl esters were examined. No differences in the rate of hydrolysis were observed between cholesteryl oleate, palmitate and linoleate. The data suggest that a single acid lipase, presumably of lysosomal origin, has broad specificity towards triglycerides and cholesteryl esters, and may play a role in the hydrolysis of these lipids during intralysosomal degradation of lipoproteins.", "contents": "Cholesteryl ester and triglyceride hydrolysis by an acid lipase from rabbit aorta. The properties of the triglyceride- and cholesteryl ester-hydrolyzing activity by an acid lipase from rabbit aortic tissue were compared under different experimental conditions. Radiolabeled cholesteryl oleate or triolein was incorporated into phospholipid vesicles by sonication and the resulting preparations were used for in vitro studies. No distinction was observed between triglyceride lipase and cholesterol esterase activity in the aortic cytosol fraction following either thermal inactivation, inhibition by a mercurial, fractionation by ammonium sulfate or acid precipitation, or DEAE-cellulose chromatography. Addition of rabbit lipoproteins to the assay system resulted in inhibition of both cholesterol esterase and triglyceride lipase activity. Parallel changes in the hydrolysis of both substrates also were observed when exogenously added lipids were added to the incubation system in various physical states. Specificities of the enzyme system towards different cholesteryl esters were examined. No differences in the rate of hydrolysis were observed between cholesteryl oleate, palmitate and linoleate. The data suggest that a single acid lipase, presumably of lysosomal origin, has broad specificity towards triglycerides and cholesteryl esters, and may play a role in the hydrolysis of these lipids during intralysosomal degradation of lipoproteins."}
{"id": "PMID:28784", "title": "A protease-like permeability factor in the guinea pig skin. 2. In vitro activation of the latent form permeability factor by weakly acidic phosphate buffer.", "content": "Conditions for the in vitro activation of the latent form of a protease-like permeability factor in the pseudoglobulin fraction from guinea pig skin were examined. (1) The factor was activated by dialysis against 67 mM phosphate buffer at pH 5.8--6.4, not at pH 7.0--8.0. (2) High salt concentration (200 mM or greater phosphate buffer or 67 mM phosphate buffer containing 200 mM or greater KCl or NaCl) prevented the activation at pH 6.2. (3) High osmotic pressure (sucrose at 1 M) did not affect activation at pH 6.2. (4) Reconversion of the activated permeability factor into an inactive form was not observed under high salt conditions, under which the latent permeability factor was stable in its own form. (5) The molecular size of the latent permeability factor was estimated as approx. 80 000 by Sephadex G-100 gel filtration at high salt concentration.", "contents": "A protease-like permeability factor in the guinea pig skin. 2. In vitro activation of the latent form permeability factor by weakly acidic phosphate buffer. Conditions for the in vitro activation of the latent form of a protease-like permeability factor in the pseudoglobulin fraction from guinea pig skin were examined. (1) The factor was activated by dialysis against 67 mM phosphate buffer at pH 5.8--6.4, not at pH 7.0--8.0. (2) High salt concentration (200 mM or greater phosphate buffer or 67 mM phosphate buffer containing 200 mM or greater KCl or NaCl) prevented the activation at pH 6.2. (3) High osmotic pressure (sucrose at 1 M) did not affect activation at pH 6.2. (4) Reconversion of the activated permeability factor into an inactive form was not observed under high salt conditions, under which the latent permeability factor was stable in its own form. (5) The molecular size of the latent permeability factor was estimated as approx. 80 000 by Sephadex G-100 gel filtration at high salt concentration."}
{"id": "PMID:28785", "title": "Aggregation of ampholine on heparin and other acidic polysaccharides in isoelectric focusing.", "content": "The mechanism of complexation of pI range 3.5--5 Ampholine to heparin in isoelectric focusing has been explored by the dye-binding technique at different pH values in solution. There is no significant interaction between heparin and Ampholine at pH 6.7. Weak, or selective, binding occurs at pH 5.1, and very strong interaction at pH 3.5. In the latter system, the Ampholine components appear to behave as polycations due to their ordered sequence of positive charges, each two methylene groups apart, which favors a strong binding to polyanions. In addition, there appear to be variable stoichiometries for the strong binding between heparin and Ampholine, depending on their relative amounts. It is proposed that at a low ratio of heparin to Ampholine (Ampholine excess), aggregation is perpendicular to the heparin chain, with the end ammonium charge of each Ampholine molecule neutralizing one negative charge along the heparin molecule; at higher ratios (heparin excess), the bound Ampholine segment is aligned parallel to the heparin molecule, so that on the average one Ampholine component neutralizes approx. three negative charges. The banding of heparin in isoelectric focusing in the pH range 3.0--4.5 can be explained by aggregation of the various components on heparin in amounts dependent upon the net charge on the Ampholine species at the given pH, and upon the changing stoichiometries as a function of the variation in ratio of heparin to Ampholine along the pH gradient. Binding of Ampholine to polygalacturonate was also demonstrated in excess Ampholine in a pH range dependent on the degree of protonation of the carboxyl groups of this acidic polysaccharide as well as on the net positive charge of the Ampholine. The aggregation seen at pH 4.2--4.5 led to the prediction and subsequent demonstration that polygalacturonate would also exhibit binding upon isoelectric focusing. This supports the hypothesis that aggregation of Ampholine on polyanions having sufficient charge density is a general phenomenon which can lead to spurious banding of certain polymers at appropriate pH ranges in isoelectric focusing. On the basis of their behavior in isoelectric focusing at pH 3.0--4.5, strength of aggregation of the polyanions studied appears to be heparin A = heparin B greather than polyglutamate greater than carboxyl-reduced heparin B greater than polygalacturonic acid.", "contents": "Aggregation of ampholine on heparin and other acidic polysaccharides in isoelectric focusing. The mechanism of complexation of pI range 3.5--5 Ampholine to heparin in isoelectric focusing has been explored by the dye-binding technique at different pH values in solution. There is no significant interaction between heparin and Ampholine at pH 6.7. Weak, or selective, binding occurs at pH 5.1, and very strong interaction at pH 3.5. In the latter system, the Ampholine components appear to behave as polycations due to their ordered sequence of positive charges, each two methylene groups apart, which favors a strong binding to polyanions. In addition, there appear to be variable stoichiometries for the strong binding between heparin and Ampholine, depending on their relative amounts. It is proposed that at a low ratio of heparin to Ampholine (Ampholine excess), aggregation is perpendicular to the heparin chain, with the end ammonium charge of each Ampholine molecule neutralizing one negative charge along the heparin molecule; at higher ratios (heparin excess), the bound Ampholine segment is aligned parallel to the heparin molecule, so that on the average one Ampholine component neutralizes approx. three negative charges. The banding of heparin in isoelectric focusing in the pH range 3.0--4.5 can be explained by aggregation of the various components on heparin in amounts dependent upon the net charge on the Ampholine species at the given pH, and upon the changing stoichiometries as a function of the variation in ratio of heparin to Ampholine along the pH gradient. Binding of Ampholine to polygalacturonate was also demonstrated in excess Ampholine in a pH range dependent on the degree of protonation of the carboxyl groups of this acidic polysaccharide as well as on the net positive charge of the Ampholine. The aggregation seen at pH 4.2--4.5 led to the prediction and subsequent demonstration that polygalacturonate would also exhibit binding upon isoelectric focusing. This supports the hypothesis that aggregation of Ampholine on polyanions having sufficient charge density is a general phenomenon which can lead to spurious banding of certain polymers at appropriate pH ranges in isoelectric focusing. On the basis of their behavior in isoelectric focusing at pH 3.0--4.5, strength of aggregation of the polyanions studied appears to be heparin A = heparin B greather than polyglutamate greater than carboxyl-reduced heparin B greater than polygalacturonic acid."}
{"id": "PMID:28786", "title": "Selective polyamine-binding proteins. Spermine binding by an androgen-sensitive phosphoprotein.", "content": "Rat ventral prostate contains an acidic protein which can bind spermine selectively. The relative binding affinities of various aliphatic amines for the protein are, in decreasing order, spermine greater than thermine greater than greater than putrecine greater than 1,10-diaminodecane, cadaverine and 1,12-diaminododecane. The binding protein has an isoelectric point at pH 4.3 and a sedimentation coefficient of 3 S. Its molecular weight is approx. 30 000. Histones and nuclear chromatin preparations of the prostate can interact with the binding protein. The spermine-binding activity of the purified prostate protein can be inactivated by treatment with intestinal alkaline phosphatases. The phosphatase treated preparation can then be reactivated by beef heart protein kinase in the presence of cyclic AMP and ATP. The spermine-binding activity of the prostate cytosol protein fraction decreases after castration, but increases very rapidly after the castrated rats are injected with 5alpha-dihydrotestosterone. This finding raises the possibility that, in the postate, certain androgen actions may be dependent on the androgen-induced increase in the acidic protein binding of polyamines and their translocation to a functional cellular site such as nuclear chromatin. In the prostate cytosol, spermine also binds to 4-S tRNAs and to a unique RNA which has a sedimentation coefficient of 1.5 S.", "contents": "Selective polyamine-binding proteins. Spermine binding by an androgen-sensitive phosphoprotein. Rat ventral prostate contains an acidic protein which can bind spermine selectively. The relative binding affinities of various aliphatic amines for the protein are, in decreasing order, spermine greater than thermine greater than greater than putrecine greater than 1,10-diaminodecane, cadaverine and 1,12-diaminododecane. The binding protein has an isoelectric point at pH 4.3 and a sedimentation coefficient of 3 S. Its molecular weight is approx. 30 000. Histones and nuclear chromatin preparations of the prostate can interact with the binding protein. The spermine-binding activity of the purified prostate protein can be inactivated by treatment with intestinal alkaline phosphatases. The phosphatase treated preparation can then be reactivated by beef heart protein kinase in the presence of cyclic AMP and ATP. The spermine-binding activity of the prostate cytosol protein fraction decreases after castration, but increases very rapidly after the castrated rats are injected with 5alpha-dihydrotestosterone. This finding raises the possibility that, in the postate, certain androgen actions may be dependent on the androgen-induced increase in the acidic protein binding of polyamines and their translocation to a functional cellular site such as nuclear chromatin. In the prostate cytosol, spermine also binds to 4-S tRNAs and to a unique RNA which has a sedimentation coefficient of 1.5 S."}
{"id": "PMID:28787", "title": "Apparent stability constants of H+ and Mg2\" complexes of 5-phosphoribosyl alpha-1-pyrophosphate.", "content": "Apparent Mg2+ and H+ stability constants of 5-phosphoribosyl alpha-1-pyrophosphate (ligand, L) complexes were determined from pH titration data at 25 degrees C with an average of 0.17 M NaCl or KCl and 0.20 M ionic strength. The logarithms of calculated macroscopic overall stability constants are: 3.2 (MgL3-), 4.8 (Mg2L-), 6.5 (HL4-), 12.4 H2L3-), 9.4 (Mg HL2-), and 11.0 (MgH2L). Comparison of the stepwise Mg2+ stability constants (log k = 3.2 and 1.6) with those of MgADP- and MgAMP or Mg-hexose-1-P suggests that the first and second Mg2+ bind to the 1-PP and 5-P groups of the ligand, respectively. Reasonable assumptions about relative microscopic constants indicate that several of the microscopic isomers do not achieve significant concentrations over a large range of conditions. Judging from other data on organophosphate complexes, it is likely that the constants of this study may be extrapolated with little error to other conditions of ionic strength 0.1--0.2 M) and temperature (e.g., 15--35 degrees C), and widely different monovalent ion concentrations.", "contents": "Apparent stability constants of H+ and Mg2\" complexes of 5-phosphoribosyl alpha-1-pyrophosphate. Apparent Mg2+ and H+ stability constants of 5-phosphoribosyl alpha-1-pyrophosphate (ligand, L) complexes were determined from pH titration data at 25 degrees C with an average of 0.17 M NaCl or KCl and 0.20 M ionic strength. The logarithms of calculated macroscopic overall stability constants are: 3.2 (MgL3-), 4.8 (Mg2L-), 6.5 (HL4-), 12.4 H2L3-), 9.4 (Mg HL2-), and 11.0 (MgH2L). Comparison of the stepwise Mg2+ stability constants (log k = 3.2 and 1.6) with those of MgADP- and MgAMP or Mg-hexose-1-P suggests that the first and second Mg2+ bind to the 1-PP and 5-P groups of the ligand, respectively. Reasonable assumptions about relative microscopic constants indicate that several of the microscopic isomers do not achieve significant concentrations over a large range of conditions. Judging from other data on organophosphate complexes, it is likely that the constants of this study may be extrapolated with little error to other conditions of ionic strength 0.1--0.2 M) and temperature (e.g., 15--35 degrees C), and widely different monovalent ion concentrations."}
{"id": "PMID:28788", "title": "3-Chloroacetylpyridine adenine dinucleotide phosphate, an alkylating analogue of NADP+.", "content": "An alkylating analogue of NADP+ the 3-chloroacetylpyridine adenine dinucleotide phosphate was prepared from 3-diazoacetylpyridine adenine dinucleotide phosphate which was obtained by enzymatic transglucosidation of NADP+. The 3-diazoacetylpyridine adenine dinucleotide phosphate proved to be more unstable when compared to the corresponding NAD+ analogue. The alkylation of several dehydrogenases using this alkylating analogue is mentioned.", "contents": "3-Chloroacetylpyridine adenine dinucleotide phosphate, an alkylating analogue of NADP+. An alkylating analogue of NADP+ the 3-chloroacetylpyridine adenine dinucleotide phosphate was prepared from 3-diazoacetylpyridine adenine dinucleotide phosphate which was obtained by enzymatic transglucosidation of NADP+. The 3-diazoacetylpyridine adenine dinucleotide phosphate proved to be more unstable when compared to the corresponding NAD+ analogue. The alkylation of several dehydrogenases using this alkylating analogue is mentioned."}
{"id": "PMID:28790", "title": "Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats.", "content": "Testosterone pretreatment (1.0-4.0 mg/kg) attenuated, in a dose-response fashion, the induction of stereotyped behavior and hyperactivity by pargyline (0.25, 4.0 mg/kg) and beta-phenylethylamine (8.0, 16.0 mg/kg) in preubertal, male rats. The dyskinetic movements induced by pargyline and beta-phenylethylamine were proposed as a possible animal model for tardive dyskinesias. Attenuation by testosterone of these effects suggested an hormonal involvement consistent with the reported predominant occurrence of tardive dyskinesias in women and in the elderly.", "contents": "Testosterone-attenuated stereotype and hyperactivity induced by beta-phenylethylamine in pargyline-pretreated rats. Testosterone pretreatment (1.0-4.0 mg/kg) attenuated, in a dose-response fashion, the induction of stereotyped behavior and hyperactivity by pargyline (0.25, 4.0 mg/kg) and beta-phenylethylamine (8.0, 16.0 mg/kg) in preubertal, male rats. The dyskinetic movements induced by pargyline and beta-phenylethylamine were proposed as a possible animal model for tardive dyskinesias. Attenuation by testosterone of these effects suggested an hormonal involvement consistent with the reported predominant occurrence of tardive dyskinesias in women and in the elderly."}
{"id": "PMID:28794", "title": "Bone marrow colony-forming cells in acute drug-induced agranulocytosis.", "content": "The capacity to differentiate and form colonies in vitro by bone marrow granulocytic precursor cells and its evolution were studied in eight cases of drug-induced acute agranulocytosis. In three cases colonies and clusters count were normal or high. These cases were probably immunological agranulocytosis. In the five other cases this number was very low and returned to normal from three to thirteen days. These were probably cases of marrow suppression by the drug.", "contents": "Bone marrow colony-forming cells in acute drug-induced agranulocytosis. The capacity to differentiate and form colonies in vitro by bone marrow granulocytic precursor cells and its evolution were studied in eight cases of drug-induced acute agranulocytosis. In three cases colonies and clusters count were normal or high. These cases were probably immunological agranulocytosis. In the five other cases this number was very low and returned to normal from three to thirteen days. These were probably cases of marrow suppression by the drug."}
{"id": "PMID:28795", "title": "Immunological profile in sarcoidosis patients. The in vitro and in vivo effect of thymic humoral factor.", "content": "A study was made of the lymphocytes obtained from 25 patients suffering from sarcoidosis as proved by the Kveim-Siltzbach test and/or organ biopsy. The number of T lymphocytes was determined by the E rosette technique and functional activity by a local xenogeneic graft-versus-host reaction (GVHR) as well as skin tests with PPD, SK-SD, Candida and Trichophyton. In most cases the absolute number of T cells was low and there was an evident impairment of their functional activity. There was also a clear correlation between the severity of impairment of cell-mediated immunity and the clinical stage and activity of the disease. In vitro incubation of the lymphocytes with thymic humoral factor resulted in recovery of the functional activity of the T lymphocytes of 4 of the 7 patients tested, with the previously negative GVHR becoming positive. One of these patients was treated with thymic humoral factor with a resulting restoration of the cell-mediated immune response although there was no evident clinical improvement.", "contents": "Immunological profile in sarcoidosis patients. The in vitro and in vivo effect of thymic humoral factor. A study was made of the lymphocytes obtained from 25 patients suffering from sarcoidosis as proved by the Kveim-Siltzbach test and/or organ biopsy. The number of T lymphocytes was determined by the E rosette technique and functional activity by a local xenogeneic graft-versus-host reaction (GVHR) as well as skin tests with PPD, SK-SD, Candida and Trichophyton. In most cases the absolute number of T cells was low and there was an evident impairment of their functional activity. There was also a clear correlation between the severity of impairment of cell-mediated immunity and the clinical stage and activity of the disease. In vitro incubation of the lymphocytes with thymic humoral factor resulted in recovery of the functional activity of the T lymphocytes of 4 of the 7 patients tested, with the previously negative GVHR becoming positive. One of these patients was treated with thymic humoral factor with a resulting restoration of the cell-mediated immune response although there was no evident clinical improvement."}
{"id": "PMID:28796", "title": "Hydrogen ion CO2 and buffer capacity in brain from water depleted rats.", "content": "pH, C02 and buffer capacity of the brain and blood acid-base status were studied in (C) control and in acutely water depleted (WD) rats. WD rats developed a greater metabolic [H+] increase in brain than in blood. The results suggest that brain [H+] change is a primary metabolic reply to acute dehydration.", "contents": "Hydrogen ion CO2 and buffer capacity in brain from water depleted rats. pH, C02 and buffer capacity of the brain and blood acid-base status were studied in (C) control and in acutely water depleted (WD) rats. WD rats developed a greater metabolic [H+] increase in brain than in blood. The results suggest that brain [H+] change is a primary metabolic reply to acute dehydration."}
{"id": "PMID:28797", "title": "Equilibrium and kinetics of the thermal unfolding of alpha-lactalbumin. The relation to its folding mechanism.", "content": "The thermal unfolding of alpha-lactalbumin has been studied by equilibrium measurements of aromatic difference spectra, and by kinetic measurements of the Joule heating temperature-jump. The unfolding at neutral pH is a reversible two-state transition. The equilibrium transition curves are analyzed by the nonlinear squares method, which gives correct values of thermodynamic parameters based on the data in a wide range of temperature. The results are discussed in relation to the previous studies on the unfolding by guanidine hydrochloride or by acid. The thermally unfolded state, a partially unfolded species, is shown to be thermodynamically similar to but not identical with the acid state. The folding pathway deduced from the kinetic results is essentially consistent with the folding model of alpha-lactalbumin proposed previously. Large decreases in entropy and in heat capacity during the reversed activation suggest the packing of the folded segments by hydrophobic interactions, while the forward activation shows a marked temperature dependence, probably caused by the disruption of specific long-range interactions.", "contents": "Equilibrium and kinetics of the thermal unfolding of alpha-lactalbumin. The relation to its folding mechanism. The thermal unfolding of alpha-lactalbumin has been studied by equilibrium measurements of aromatic difference spectra, and by kinetic measurements of the Joule heating temperature-jump. The unfolding at neutral pH is a reversible two-state transition. The equilibrium transition curves are analyzed by the nonlinear squares method, which gives correct values of thermodynamic parameters based on the data in a wide range of temperature. The results are discussed in relation to the previous studies on the unfolding by guanidine hydrochloride or by acid. The thermally unfolded state, a partially unfolded species, is shown to be thermodynamically similar to but not identical with the acid state. The folding pathway deduced from the kinetic results is essentially consistent with the folding model of alpha-lactalbumin proposed previously. Large decreases in entropy and in heat capacity during the reversed activation suggest the packing of the folded segments by hydrophobic interactions, while the forward activation shows a marked temperature dependence, probably caused by the disruption of specific long-range interactions."}
{"id": "PMID:28798", "title": "Continuous fractionation of human plasma.", "content": "Continuous processing has been applied to human plasma fractionation by the cold ethanol process. On-line pH control of +/- 0.05 pH units, flow control of +/- 1%, and temperature control of +/- 0.5 degree C have been achieved. Optimization of precipitation pHs has been carried out for purifying plasma protein fractions and albumin. During precipitation, the irreversible nature of the pH overshoots has been demonstrated. Compared to the batch processing mode, the continuous scheme produces an increased yield between 6 to 11%.", "contents": "Continuous fractionation of human plasma. Continuous processing has been applied to human plasma fractionation by the cold ethanol process. On-line pH control of +/- 0.05 pH units, flow control of +/- 1%, and temperature control of +/- 0.5 degree C have been achieved. Optimization of precipitation pHs has been carried out for purifying plasma protein fractions and albumin. During precipitation, the irreversible nature of the pH overshoots has been demonstrated. Compared to the batch processing mode, the continuous scheme produces an increased yield between 6 to 11%."}
{"id": "PMID:28799", "title": "Toxic effects of fatty acids on yeast cells: possible mechanisms of action.", "content": "As shown in a previous paper, threshold concentrations of lower and intermediate fatty acids inhibit the uptake of inorganic phosphate, growth, and cell division in yeast cells. This demonstrates that, apart from these effects, the acids cause an increase in the respiration quotient (RQ), inhibition of CO2 fixation, production of ethanol at the expense of anabolic processes, and inhibition of active amino acid transport in the yeast Candida utilis. On the other hand, the threshold concentrations have no effect on intracellular pH. The inhibition of the inorganic phosphate uptake cannot be the sole primary mode of action of fatty acids since the omission of inorganic phosphate in the incubation medium brings about an inhibition of anabolic processes that is lower than that brought about by fatty acids since the omission of inorganic phosphate in the incubation medium brings about an inhibition of anabolic processes that is lower than that brought by fatty acids at concentrations still premitting some phosphate uptake. Although 2,4-dinitrophenol and caproic acid at low concentrations cause an analogous decrease in biomass yield, their combination does not bring about any marked increase in the effect. Considering the physicochemical properties of fatty acids and their preferential action on energy-requiring processes, one of the key sites of action can be assumed to be the mitochondrial membrane. Fatty acids might inhibit the transport of anions, especially phosphate, across the membrane, and disturb the membrane potential by affecting the transport protons. The physiocochemical properties of fatty acids may also give rise to their binding to other intracellular membranes and to a subsequent interference with the function of the corresponding organelles.", "contents": "Toxic effects of fatty acids on yeast cells: possible mechanisms of action. As shown in a previous paper, threshold concentrations of lower and intermediate fatty acids inhibit the uptake of inorganic phosphate, growth, and cell division in yeast cells. This demonstrates that, apart from these effects, the acids cause an increase in the respiration quotient (RQ), inhibition of CO2 fixation, production of ethanol at the expense of anabolic processes, and inhibition of active amino acid transport in the yeast Candida utilis. On the other hand, the threshold concentrations have no effect on intracellular pH. The inhibition of the inorganic phosphate uptake cannot be the sole primary mode of action of fatty acids since the omission of inorganic phosphate in the incubation medium brings about an inhibition of anabolic processes that is lower than that brought about by fatty acids since the omission of inorganic phosphate in the incubation medium brings about an inhibition of anabolic processes that is lower than that brought by fatty acids at concentrations still premitting some phosphate uptake. Although 2,4-dinitrophenol and caproic acid at low concentrations cause an analogous decrease in biomass yield, their combination does not bring about any marked increase in the effect. Considering the physicochemical properties of fatty acids and their preferential action on energy-requiring processes, one of the key sites of action can be assumed to be the mitochondrial membrane. Fatty acids might inhibit the transport of anions, especially phosphate, across the membrane, and disturb the membrane potential by affecting the transport protons. The physiocochemical properties of fatty acids may also give rise to their binding to other intracellular membranes and to a subsequent interference with the function of the corresponding organelles."}
{"id": "PMID:28802", "title": "[Status of T- and B-lymphocytes in long living CBA--F1 (CBA X C57BL/6) chimeras].", "content": "Semiallogeneic chimeras were produced by injecting 3 X 10(7) spleen cells of mice CBA (H--2k, Mlsd) to lethally irradiated mice (CBA X C57BL/6)F1. Two days later recipients were given cyclophosphamide (CP), 2 mg per mouse, to prevent death of graft versus host reaction (GVHR). For 1.5--2 months after the creation of chimerism in 23 of 26 mice under study all cells producing antibodies to SRBC were represented by donor cells of H-2 phenotype; 3 mice were partial chimeras. Spontaneous blast transformation in the cultures of chimera spleen did not exceed the control level, and in the mixed lymphocyte culture chimera cells failed to proliferate on addition of irradiated lymphocytes (CBA X C57BL/6) F1. At the same time chimera gave intensive blast transformation to the irradiated lymphocytes of the third line of mice DBA/2 (H--2d, Mlsa). Among the chimera spleen cells no killers capable of destroying target cells of donor or recipient origin were revealed. Similar results were obtained in vivo: chimera cells gave no positive local GVHR after administration to mice (CBA X C57BL/6) F1. Prolonged chimerism was accompanied by a reactivity of donor T-lymphocytes to the recipient transplantation antigens. A blocking factor was revealed in the blood serum of chimeras. The substitution of donor lymphocytes for the recipient cells begins after 3 to 5 months. At the same period donor T-cell population reconstitutes partially the responsiveness to the recipient antigens and the blocking factor disappears from chimeras blood.", "contents": "[Status of T- and B-lymphocytes in long living CBA--F1 (CBA X C57BL/6) chimeras]. Semiallogeneic chimeras were produced by injecting 3 X 10(7) spleen cells of mice CBA (H--2k, Mlsd) to lethally irradiated mice (CBA X C57BL/6)F1. Two days later recipients were given cyclophosphamide (CP), 2 mg per mouse, to prevent death of graft versus host reaction (GVHR). For 1.5--2 months after the creation of chimerism in 23 of 26 mice under study all cells producing antibodies to SRBC were represented by donor cells of H-2 phenotype; 3 mice were partial chimeras. Spontaneous blast transformation in the cultures of chimera spleen did not exceed the control level, and in the mixed lymphocyte culture chimera cells failed to proliferate on addition of irradiated lymphocytes (CBA X C57BL/6) F1. At the same time chimera gave intensive blast transformation to the irradiated lymphocytes of the third line of mice DBA/2 (H--2d, Mlsa). Among the chimera spleen cells no killers capable of destroying target cells of donor or recipient origin were revealed. Similar results were obtained in vivo: chimera cells gave no positive local GVHR after administration to mice (CBA X C57BL/6) F1. Prolonged chimerism was accompanied by a reactivity of donor T-lymphocytes to the recipient transplantation antigens. A blocking factor was revealed in the blood serum of chimeras. The substitution of donor lymphocytes for the recipient cells begins after 3 to 5 months. At the same period donor T-cell population reconstitutes partially the responsiveness to the recipient antigens and the blocking factor disappears from chimeras blood."}
{"id": "PMID:28806", "title": "The effects of uptake1 on alpha-adrenoceptor antagonist potency in dog saphenous vein.", "content": "1 The effects of alpha-adrenoceptor antagonists on contractile responses to noradrenaline and methoxamine were examined in isolated saphenous vein strips of the dog. 2 Phentolamine, labetalol and thymoxamine antagonized responses to methoxamine to a greater extent than responses to noradrenaline. 3 Cocaine (3.0 x 10(-5) mol/l) increased the potency of noradrenaline by about eight fold, but had little or no effect on the potency of methoxamine. 4 In the presence of cocaine (3.0 x 10(-5) mol/l) the potency of the antagonists against noradrenaline was increased such that the pA2 values were then similar to those obtained against methoxamine. 5 It is concluded that the lower potency of phentolamine, labetalol and thymoxamine as antagonists of noradrenaline than of methoxamine is due to the presence of an avid saturable uptake1 process in the saphenous vein.", "contents": "The effects of uptake1 on alpha-adrenoceptor antagonist potency in dog saphenous vein. 1 The effects of alpha-adrenoceptor antagonists on contractile responses to noradrenaline and methoxamine were examined in isolated saphenous vein strips of the dog. 2 Phentolamine, labetalol and thymoxamine antagonized responses to methoxamine to a greater extent than responses to noradrenaline. 3 Cocaine (3.0 x 10(-5) mol/l) increased the potency of noradrenaline by about eight fold, but had little or no effect on the potency of methoxamine. 4 In the presence of cocaine (3.0 x 10(-5) mol/l) the potency of the antagonists against noradrenaline was increased such that the pA2 values were then similar to those obtained against methoxamine. 5 It is concluded that the lower potency of phentolamine, labetalol and thymoxamine as antagonists of noradrenaline than of methoxamine is due to the presence of an avid saturable uptake1 process in the saphenous vein."}
{"id": "PMID:28807", "title": "The effects of alpha-adrenoceptor antagonists on contractile responses to 5-hydroxytryptamine in dog saphenous vein.", "content": "1 5-Hydroxytryptamine (5-HT) contracted isolated saphenous vein strips of the dog, producing a biphasic concentration-effect curve. The first phase occurred with low concentrations of 5-HT (1.0 X 10(-8) TO 5.0 X 10(-6) mol/l) with a plateau between 1.0 x 10(-6) mol/l and 1.0 x 10(-5) mol/l. The second phase occurred with high concentrations of 5-HT (greater than 1.0 x 10(-5) mol/l). 2 The alpha-adrenoceptor antabonists, phentolamine (5.0 x 10(-8) to 5.0 x 10(-7) mol/l), labetalol (1.0 x 10(-6) to 1.0 x 10(-5) mol/l) and thymoxamine (1.0 x 10(-6) to 1.0 x 10(-5) mol/l), antagonized responses to high concentrations of 5-HT but responses to low concentrations of 5-HT were not antagonized. 3 The effects of high concentrations of 5-HT were antagonized by cocaine (1.0 x 10(-6) to 1.0 x 10(-5) mol/l) and were not evident in veins removed from dogs pretreated with syrosingopine. 5-HT receptors and that high concentrations of 5-HT also act indirectly on alpha-adrenoceptors by displacing noradrenaline from neuronal stores.", "contents": "The effects of alpha-adrenoceptor antagonists on contractile responses to 5-hydroxytryptamine in dog saphenous vein. 1 5-Hydroxytryptamine (5-HT) contracted isolated saphenous vein strips of the dog, producing a biphasic concentration-effect curve. The first phase occurred with low concentrations of 5-HT (1.0 X 10(-8) TO 5.0 X 10(-6) mol/l) with a plateau between 1.0 x 10(-6) mol/l and 1.0 x 10(-5) mol/l. The second phase occurred with high concentrations of 5-HT (greater than 1.0 x 10(-5) mol/l). 2 The alpha-adrenoceptor antabonists, phentolamine (5.0 x 10(-8) to 5.0 x 10(-7) mol/l), labetalol (1.0 x 10(-6) to 1.0 x 10(-5) mol/l) and thymoxamine (1.0 x 10(-6) to 1.0 x 10(-5) mol/l), antagonized responses to high concentrations of 5-HT but responses to low concentrations of 5-HT were not antagonized. 3 The effects of high concentrations of 5-HT were antagonized by cocaine (1.0 x 10(-6) to 1.0 x 10(-5) mol/l) and were not evident in veins removed from dogs pretreated with syrosingopine. 5-HT receptors and that high concentrations of 5-HT also act indirectly on alpha-adrenoceptors by displacing noradrenaline from neuronal stores."}
{"id": "PMID:28808", "title": "The effects of piperoxan on uptake of noradrenaline and overflow of transmitter in the isolated blood perfused spleen of the cat.", "content": "1 The competitive alpha-adrenoceptor blocking agent, piperoxan, in concentrations up to 2 x 10(-4) M, produced large dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz. 2 At concentrations greater than 2 x 10(-4) M, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose-dependent decrease in transmitter overflow. 3 Phenoxybenzamine (10(-4) M) and desmethylimipramine (3 x 10(-5) M) produced further increases in transmitter overflow when added after piperoxan. 4 Piperoxan (5.8 to 6.6 x 10(-6) M) had no effect on the recovery of 3H in the venous blood following the close arterial infusion or injection of (3H)-(--)-noradrenaline, indicating that the drug does not inhibit uptake of the amine. 5 Piperoxan produced dose-dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 microgram of (--)-noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 x 10(-6) M piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation. 6 In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose-response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens.", "contents": "The effects of piperoxan on uptake of noradrenaline and overflow of transmitter in the isolated blood perfused spleen of the cat. 1 The competitive alpha-adrenoceptor blocking agent, piperoxan, in concentrations up to 2 x 10(-4) M, produced large dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz. 2 At concentrations greater than 2 x 10(-4) M, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose-dependent decrease in transmitter overflow. 3 Phenoxybenzamine (10(-4) M) and desmethylimipramine (3 x 10(-5) M) produced further increases in transmitter overflow when added after piperoxan. 4 Piperoxan (5.8 to 6.6 x 10(-6) M) had no effect on the recovery of 3H in the venous blood following the close arterial infusion or injection of (3H)-(--)-noradrenaline, indicating that the drug does not inhibit uptake of the amine. 5 Piperoxan produced dose-dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 microgram of (--)-noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 x 10(-6) M piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation. 6 In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose-response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens."}
{"id": "PMID:28810", "title": "Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension.", "content": "Atenolol was compared with five other beta-blockers and a thiazide diuretic in a randomised cross-over trial of once-daily treatment of essential hypertension. Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects. Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects, suggesting that further increases in dosage might be effective and well tolerated. Labetalol proved ineffective when given once daily, and the high incidence of side effects, equalled only by pindolol, would probably prohibit further increases in dosage. Bendrofluazide was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure, and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension.", "contents": "Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension. Atenolol was compared with five other beta-blockers and a thiazide diuretic in a randomised cross-over trial of once-daily treatment of essential hypertension. Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects. Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects, suggesting that further increases in dosage might be effective and well tolerated. Labetalol proved ineffective when given once daily, and the high incidence of side effects, equalled only by pindolol, would probably prohibit further increases in dosage. Bendrofluazide was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure, and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension."}
{"id": "PMID:28811", "title": "Need for beta-blockade in hypertension reduced with long-term minoxidil.", "content": "Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients.", "contents": "Need for beta-blockade in hypertension reduced with long-term minoxidil. Sequential changes in plasma renin activity and urinary aldosterone and noradrenaline were assessed in eight patients with severe hypertension after minoxidil had been added to their treatment. Doses of 2.5--27.5 (mean 12.5) mg/day reduced the mean blood pressure from 166/113 +/-6/2 mm Hg to 124/88+/-4/2 mm Hg in one week. Plasma renin activity and urinary aldosterone and noradrenaline increased twofold to threefold initially but returned to baseline values within two to three weeks and remained unchanged during a mean follow-up of 5.1 months. Beta-blocking drugs were then withdrawn slowly in six patients without adverse effects, though blood pressure and heart rate increased in three patients, who required minimal doses of beta-blockers. Plasma renin activity and urinary aldosterone and noradrenaline did not change significantly after beta-blockade had been stopped. We conclude that the need for beta-blockade is greatly reduced with long-term minoxidil treatment and that it may be unnecessary in some patients."}
{"id": "PMID:28814", "title": "Transmitter histochemistry of the rat olfactory bulb. II. Fluorescence histochemical, autoradiographic and electron microscopic localization of monoamines.", "content": "The rat olfactory bulb was studied with the Falck-Hillarp formaldehyde fluorescence technique, including recent modifications, autoradiography and electron microscopic cytochemistry (permanganate fixation). Some periglomerular cells and few superficial tufted cells take up and accumulate catecholamines and precursors. They probably represent dopamine cells. In the glomeruli, probable 5-hydroxy-tryptamine nerve terminals could be identified. In the granular and external plexiform layers, noradrenaline axon terminals were present. At the ultrastructural level, monoamine boutons were in synaptic contact with dendritic spines of granule cells and in the glomeruli, probable 5-hydroxytryptamine boutons formed synapses with periglomerular cell dendrites. Therefore, monoamine afferents to the bulb may exert their influence via interneurons.", "contents": "Transmitter histochemistry of the rat olfactory bulb. II. Fluorescence histochemical, autoradiographic and electron microscopic localization of monoamines. The rat olfactory bulb was studied with the Falck-Hillarp formaldehyde fluorescence technique, including recent modifications, autoradiography and electron microscopic cytochemistry (permanganate fixation). Some periglomerular cells and few superficial tufted cells take up and accumulate catecholamines and precursors. They probably represent dopamine cells. In the glomeruli, probable 5-hydroxy-tryptamine nerve terminals could be identified. In the granular and external plexiform layers, noradrenaline axon terminals were present. At the ultrastructural level, monoamine boutons were in synaptic contact with dendritic spines of granule cells and in the glomeruli, probable 5-hydroxytryptamine boutons formed synapses with periglomerular cell dendrites. Therefore, monoamine afferents to the bulb may exert their influence via interneurons."}
{"id": "PMID:28817", "title": "Kainic acid lesions of the striatum: behavioural sequalae similar to Huntington's chorea.", "content": "Kainic acid (3 nmoles bilaterally) was injected into the dorsal striatum of the rat producing virtually complete destruction of cell bodies in this structure but without directly affecting the dopamine terminals ascending from the substantia nigra and terminating in the striatum. Other fibres of passage, such as the internal capsule, were also spared. The locomotor and stereotypy responses to doses of amphetamine, a dopamine releasing agent, were found to be consistently enhanced after this lesion. The stereotypy and locomotor activity in response to the direct receptor agonist, apomorphine, however were not consistently affected. The results are interpreted in terms of a functional dichotomy between dorsal and ventral striatum and in terms of previously demonstrated electrophysiological alterations in the striatonigral feedback loop after kainic acid injection. Similarities are noted with the effects of these two stimulant drugs in human patients with Huntington's disease, thus strengthening the kainic acid animal model of this disease, first proposed on biochemical grounds.", "contents": "Kainic acid lesions of the striatum: behavioural sequalae similar to Huntington's chorea. Kainic acid (3 nmoles bilaterally) was injected into the dorsal striatum of the rat producing virtually complete destruction of cell bodies in this structure but without directly affecting the dopamine terminals ascending from the substantia nigra and terminating in the striatum. Other fibres of passage, such as the internal capsule, were also spared. The locomotor and stereotypy responses to doses of amphetamine, a dopamine releasing agent, were found to be consistently enhanced after this lesion. The stereotypy and locomotor activity in response to the direct receptor agonist, apomorphine, however were not consistently affected. The results are interpreted in terms of a functional dichotomy between dorsal and ventral striatum and in terms of previously demonstrated electrophysiological alterations in the striatonigral feedback loop after kainic acid injection. Similarities are noted with the effects of these two stimulant drugs in human patients with Huntington's disease, thus strengthening the kainic acid animal model of this disease, first proposed on biochemical grounds."}
{"id": "PMID:28820", "title": "The isolation and identification of 2,4-diketones present in human and animal tissues and in urine.", "content": "The chemical isolation of 2,3-diketone fraction from hydrolysates of various mammalian tissues has been accomplished by the use of a modified Girard T procedure. This fraction, which constitutes a new lipid class, has been resolved by gas chromatography into a number of homologous 2,4-diketones, ranging in chain length from C13 to C25. After separation by preparative gas chromatography, the following compounds have been unequivocally identified: 2,4-heptadecanedione, 2,4-nonadecanedione, 2,4-heneicosanedione, 2,4-docosanedione, and delta12-2,4-heneicosenedione. The 2,4-diketones appear to exist in tissues in the free state or in labile combination. They are present also in human urine.", "contents": "The isolation and identification of 2,4-diketones present in human and animal tissues and in urine. The chemical isolation of 2,3-diketone fraction from hydrolysates of various mammalian tissues has been accomplished by the use of a modified Girard T procedure. This fraction, which constitutes a new lipid class, has been resolved by gas chromatography into a number of homologous 2,4-diketones, ranging in chain length from C13 to C25. After separation by preparative gas chromatography, the following compounds have been unequivocally identified: 2,4-heptadecanedione, 2,4-nonadecanedione, 2,4-heneicosanedione, 2,4-docosanedione, and delta12-2,4-heneicosenedione. The 2,4-diketones appear to exist in tissues in the free state or in labile combination. They are present also in human urine."}
{"id": "PMID:28821", "title": "Kinetics of formation of the primary compound (compound I) from hydrogen peroxide and turnip peroxidases.", "content": "A kinetic study of the reaction of two turnip peroxidases (P1 and P7) with hydrogen peroxide to form the primary oxidized compound (compound I) has been carried out over the pH range from 2.4 to 10.8. In the neutral and acidic pH regions, the rates depend linearly on hydrogen peroxide concentration whereas at alkaline pH values the rates display saturation kinetics. A compound is made with the cyanide binding reaction to peroxidases since the two reactions are influenced in the same manner by ionization of groups on the native enzymes. Two different ionization processes of peroxidase P1 with pKa values of 3.9 and 10 are required to explain the rate pH profile for the reaction with H2O2. Protonation of the former group and ionization of the latter causes a decrease in the rate of reaction of the enzyme with H2O2. In the case of peroxidase P7 a minimum model involves three ionizable groups with pKa values of 2.5, 4 and 9. Protonation of the former two groups and ionization of the latter lowers the reaction rate. In the pH-independent region, the rate of formation of compound I was measured as a function of temperature. From the Arhenius plots the activation energy for the reaction was calculated to be 2.9 +/- 0.1 kcal/mol for P1 and 5.4 +/- 0.3 kcal/mol for P7. However, the rates are independent of viscosity in glycerol-water mixtures up to 30% glycerol.", "contents": "Kinetics of formation of the primary compound (compound I) from hydrogen peroxide and turnip peroxidases. A kinetic study of the reaction of two turnip peroxidases (P1 and P7) with hydrogen peroxide to form the primary oxidized compound (compound I) has been carried out over the pH range from 2.4 to 10.8. In the neutral and acidic pH regions, the rates depend linearly on hydrogen peroxide concentration whereas at alkaline pH values the rates display saturation kinetics. A compound is made with the cyanide binding reaction to peroxidases since the two reactions are influenced in the same manner by ionization of groups on the native enzymes. Two different ionization processes of peroxidase P1 with pKa values of 3.9 and 10 are required to explain the rate pH profile for the reaction with H2O2. Protonation of the former group and ionization of the latter causes a decrease in the rate of reaction of the enzyme with H2O2. In the case of peroxidase P7 a minimum model involves three ionizable groups with pKa values of 2.5, 4 and 9. Protonation of the former two groups and ionization of the latter lowers the reaction rate. In the pH-independent region, the rate of formation of compound I was measured as a function of temperature. From the Arhenius plots the activation energy for the reaction was calculated to be 2.9 +/- 0.1 kcal/mol for P1 and 5.4 +/- 0.3 kcal/mol for P7. However, the rates are independent of viscosity in glycerol-water mixtures up to 30% glycerol."}
{"id": "PMID:28822", "title": "Properties of poly(ADP-ribose) synthetase from rat pancreas and poly(ADP-ribosylation) of basic nuclear proteins.", "content": "The isolated nuclei of rat pancreas contain an enzyme system that will incorporate 3H-labeled NAD into an acid-insoluble product, which is shown to be poly(ADP-ribose). The enzyme has an optimum pH of 7.8 and the optimum temperature is between 20 and 30 degrees C. Optimum Mg2+ concentration is 8 mM and dithiothreitol also stimulates the enzyme at a concentration of 8 mM. Under standard conditions, the Km value for the reaction is 0.25 mM and an inhibition by the substrate is observed at high substrate concentrations. It has also been found that only one basic nuclear protein, that is, histone H1, is modified by the synthetase. An average chain length of 5.0 is found in the nuclei and of 4.5 on histone H1. Radioautographic studies show that poly(ADP-ribose) is closely associated with chromatin.", "contents": "Properties of poly(ADP-ribose) synthetase from rat pancreas and poly(ADP-ribosylation) of basic nuclear proteins. The isolated nuclei of rat pancreas contain an enzyme system that will incorporate 3H-labeled NAD into an acid-insoluble product, which is shown to be poly(ADP-ribose). The enzyme has an optimum pH of 7.8 and the optimum temperature is between 20 and 30 degrees C. Optimum Mg2+ concentration is 8 mM and dithiothreitol also stimulates the enzyme at a concentration of 8 mM. Under standard conditions, the Km value for the reaction is 0.25 mM and an inhibition by the substrate is observed at high substrate concentrations. It has also been found that only one basic nuclear protein, that is, histone H1, is modified by the synthetase. An average chain length of 5.0 is found in the nuclei and of 4.5 on histone H1. Radioautographic studies show that poly(ADP-ribose) is closely associated with chromatin."}
{"id": "PMID:28823", "title": "The effect of acid--base changes on skeletal muscle twitch tension.", "content": "The effects of acid--base alterations produced by changing bicarbonate (metabolic type), carbon dioxide tension (respiratory type), or both bicarbonate and carbon dioxide tension (compensated type) on skeletal muscle twitch tension, intracellular pH, and intracellular potassium were studied in vitro. Hemidiaphragm muscles from normal rats and rats fed a potassium-deficient diet were used. Decreasing the extracellular pH by decreasing bicarbonate or increasing CO2 in the bathing fluid produced a decrease in intracellular pH, intracellular K+, and muscle twitch tension. However, at a constant extracellular pH, an increase in CO2 (compensated by an increase in bicarbonate) produced an increase in intracellular K+ and twitch tension in spite of a decrease in intracellular pH. The effect on twitch tension of the hemidiaphragms showed a rapid onset, was reversible, persisted until the buffer composition was changed, and was independent of synaptic transmission. It is concluded that the twitch tension of the skeletal muscle decrease with a decrease in intracellular K+. The muscle tension also decreases with an increase in the ratio of intracellular and extracellular H+ concentration. However, there is no consistent relationship between muscle tension and extracellular or intracellular pH. The muscle tension of the diaphragms taken from K+-deficient rats is more sensitive to variations in CO2, PH, and bicarbonate concentration of the medium than that of the control rat diaphragms.", "contents": "The effect of acid--base changes on skeletal muscle twitch tension. The effects of acid--base alterations produced by changing bicarbonate (metabolic type), carbon dioxide tension (respiratory type), or both bicarbonate and carbon dioxide tension (compensated type) on skeletal muscle twitch tension, intracellular pH, and intracellular potassium were studied in vitro. Hemidiaphragm muscles from normal rats and rats fed a potassium-deficient diet were used. Decreasing the extracellular pH by decreasing bicarbonate or increasing CO2 in the bathing fluid produced a decrease in intracellular pH, intracellular K+, and muscle twitch tension. However, at a constant extracellular pH, an increase in CO2 (compensated by an increase in bicarbonate) produced an increase in intracellular K+ and twitch tension in spite of a decrease in intracellular pH. The effect on twitch tension of the hemidiaphragms showed a rapid onset, was reversible, persisted until the buffer composition was changed, and was independent of synaptic transmission. It is concluded that the twitch tension of the skeletal muscle decrease with a decrease in intracellular K+. The muscle tension also decreases with an increase in the ratio of intracellular and extracellular H+ concentration. However, there is no consistent relationship between muscle tension and extracellular or intracellular pH. The muscle tension of the diaphragms taken from K+-deficient rats is more sensitive to variations in CO2, PH, and bicarbonate concentration of the medium than that of the control rat diaphragms."}
{"id": "PMID:28825", "title": "Effect of autonomic agents on the amount of androgen-dependent granules in convoluted tubular cells of the mouse submandibular gland.", "content": "The convoluted tubular cells of the male mouse submandibular gland contain many serous-like granules in their apical cytoplasm. The autonomic regulation of the secretory process of the contents of these granules was studied by the following two methods: (1) immunochemical method using an antiserum specific to the granular components; and (2) histometric observations using light and electron microscopes. The results obtained by these two methods were well in agreement. When male mice were administered either phenylephrine or norepinephrine, the amount of granules in the glands significantly decreased. These two adrenergic stimulators were very effective, whereas synephrine was less effective. When mice were injected with a beta-adrenergic agent(isoproterenol) or a parasympathomimetic agent (pilocarpine), the amount of granules in the glands did not change. The alpha-adrenergic blockers phenoxybenzamine and phentolamine almost completely neutralized the effect of alpha-adrenergic agents on the glands, whereas another alpha-blocker (ergotamine) was less effective. These facts suggest that the secretion of the granular components is mediated by way of alpha-adrenergic receptor sites in the glands.", "contents": "Effect of autonomic agents on the amount of androgen-dependent granules in convoluted tubular cells of the mouse submandibular gland. The convoluted tubular cells of the male mouse submandibular gland contain many serous-like granules in their apical cytoplasm. The autonomic regulation of the secretory process of the contents of these granules was studied by the following two methods: (1) immunochemical method using an antiserum specific to the granular components; and (2) histometric observations using light and electron microscopes. The results obtained by these two methods were well in agreement. When male mice were administered either phenylephrine or norepinephrine, the amount of granules in the glands significantly decreased. These two adrenergic stimulators were very effective, whereas synephrine was less effective. When mice were injected with a beta-adrenergic agent(isoproterenol) or a parasympathomimetic agent (pilocarpine), the amount of granules in the glands did not change. The alpha-adrenergic blockers phenoxybenzamine and phentolamine almost completely neutralized the effect of alpha-adrenergic agents on the glands, whereas another alpha-blocker (ergotamine) was less effective. These facts suggest that the secretion of the granular components is mediated by way of alpha-adrenergic receptor sites in the glands."}
{"id": "PMID:28827", "title": "Recent developments in the supportive therapy of acute myelogenous leukemia.", "content": "The prognosis for patients with AML is improving, but mortality due to bleeding and infection remains significant. HLA compatibility has been the cornerstone of matching for prophylactic platelet transfusion; while HLA matched platelets are often of benefit, we have observed that HLA matching does not reliably predict transfusion responses. The platelet migration inhibition assay is, however, consistently predictive. The matching problem may be circumvented by the use of frozen autologous platelets, which circulate and function hemostatically. In the granulocytopenic patient with de novo fever (frequently due to bacterial sepsis), the immediate empiric use of broad spectrum antibiotics is mandatory. If the marrow begins to recover from chemotherapy shortly after the onset of infection, such that the peripheral granulocyte count will approach normal within 10 days, the likelihood of survival from an episode of septicemia after antibiosis now approaches 80%. If the marrow does not recover shortly, however, the likelihood of survival with antibiosis alone is poor. In this setting, survival is improved if patients are given granulocyte transfusions in addition to antibiotics. Patients who receive chemotherapy in a laminar air-flow room (LAFR) experience fewer severe infections than do patients in a conventional ward. However, most patients who are unresponsive to initial chemotherapy remain so in spite of protection from infection. Thus, the available results do not suggest that the LAFR is likely to improve appreciably the rate or duration of remission. Using malignant lymphoma as a model, we have found that cryopreserved autologous marrow infusions can hasten hematopoietic recovery in man after high-dose chemotherapy, and earlier reconstitution may be of clinical benefit to the patient; techniques are at hand that might permit the application of this concept to AML.", "contents": "Recent developments in the supportive therapy of acute myelogenous leukemia. The prognosis for patients with AML is improving, but mortality due to bleeding and infection remains significant. HLA compatibility has been the cornerstone of matching for prophylactic platelet transfusion; while HLA matched platelets are often of benefit, we have observed that HLA matching does not reliably predict transfusion responses. The platelet migration inhibition assay is, however, consistently predictive. The matching problem may be circumvented by the use of frozen autologous platelets, which circulate and function hemostatically. In the granulocytopenic patient with de novo fever (frequently due to bacterial sepsis), the immediate empiric use of broad spectrum antibiotics is mandatory. If the marrow begins to recover from chemotherapy shortly after the onset of infection, such that the peripheral granulocyte count will approach normal within 10 days, the likelihood of survival from an episode of septicemia after antibiosis now approaches 80%. If the marrow does not recover shortly, however, the likelihood of survival with antibiosis alone is poor. In this setting, survival is improved if patients are given granulocyte transfusions in addition to antibiotics. Patients who receive chemotherapy in a laminar air-flow room (LAFR) experience fewer severe infections than do patients in a conventional ward. However, most patients who are unresponsive to initial chemotherapy remain so in spite of protection from infection. Thus, the available results do not suggest that the LAFR is likely to improve appreciably the rate or duration of remission. Using malignant lymphoma as a model, we have found that cryopreserved autologous marrow infusions can hasten hematopoietic recovery in man after high-dose chemotherapy, and earlier reconstitution may be of clinical benefit to the patient; techniques are at hand that might permit the application of this concept to AML."}
{"id": "PMID:28828", "title": "Marrow transplantation for acute leukemia.", "content": "Marrow transplantation enables the physician to ignore the complications of marrow toxicity which limit the chemotherapy of leukemia and makes it possible to explore new drugs and regimens. The results of marrow transplantation for 154 cases of end-stage acute leukemia carried out by the Seattle Marrow Transplant Team are summarized. Even with the use of an HLA matched sibling as a donor, allogeneic marrow transplantation is followed by graft-versus-host disease in about 2/3 of the patients which is of life-threatening severity in approximately 20%. An actuarial plot of the recurrence rate of leukemia following transplantation shows that about 2/3 of the recipients of either allogeneic or syngeneic (identical twin) marrow will relapse within 2 years. However, about 1/3 will not relapse and recurrence of leukemia has not been observed after 2 years. A Kaplan-Meier plot of the survival of 29 syngeneic marrow recipients and 110 recipients of allogeneic marrow shows an almost flat survival curve in the period f om 2 to 7 years after transplantation. The leukemia free survival of these patients on no maintenance chemotherapy constitutes an operational definition of cure in these patients.", "contents": "Marrow transplantation for acute leukemia. Marrow transplantation enables the physician to ignore the complications of marrow toxicity which limit the chemotherapy of leukemia and makes it possible to explore new drugs and regimens. The results of marrow transplantation for 154 cases of end-stage acute leukemia carried out by the Seattle Marrow Transplant Team are summarized. Even with the use of an HLA matched sibling as a donor, allogeneic marrow transplantation is followed by graft-versus-host disease in about 2/3 of the patients which is of life-threatening severity in approximately 20%. An actuarial plot of the recurrence rate of leukemia following transplantation shows that about 2/3 of the recipients of either allogeneic or syngeneic (identical twin) marrow will relapse within 2 years. However, about 1/3 will not relapse and recurrence of leukemia has not been observed after 2 years. A Kaplan-Meier plot of the survival of 29 syngeneic marrow recipients and 110 recipients of allogeneic marrow shows an almost flat survival curve in the period f om 2 to 7 years after transplantation. The leukemia free survival of these patients on no maintenance chemotherapy constitutes an operational definition of cure in these patients."}
{"id": "PMID:28829", "title": "Effects of cysteine upon tumor cells.", "content": "Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport.", "contents": "Effects of cysteine upon tumor cells. Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport."}
{"id": "PMID:28857", "title": "Polyvalent pneumococcal polysaccharide vaccines.", "content": "A 14-valent pneumococcal vaccine has recently been licensed for general use after extensive testing in human subjects. Antibody production was satisfactory in 92% of individuals and a highly significant (76-92%) reduction was found in the rates for pneumococcal pneumonias caused by the capsular types present in the vaccine. Children over 2 years of age respond well to the vaccine, but younger children may not respond satisfactorily to some capsular types. In adults, the duration of the protective effect is at present unknown, but no substantial booster response was seen after a second dose at 1 year. Such a booster dose, in fact, induced a marked increase in the degree of local reaction at the injection site.", "contents": "Polyvalent pneumococcal polysaccharide vaccines. A 14-valent pneumococcal vaccine has recently been licensed for general use after extensive testing in human subjects. Antibody production was satisfactory in 92% of individuals and a highly significant (76-92%) reduction was found in the rates for pneumococcal pneumonias caused by the capsular types present in the vaccine. Children over 2 years of age respond well to the vaccine, but younger children may not respond satisfactorily to some capsular types. In adults, the duration of the protective effect is at present unknown, but no substantial booster response was seen after a second dose at 1 year. Such a booster dose, in fact, induced a marked increase in the degree of local reaction at the injection site."}
{"id": "PMID:28858", "title": "Use of a sulfate: hydrogen sulfate buffer to preserve urine for steroid analysis.", "content": "1. HCI, commonly used to preserve urine for steroid analysis, cannot safely be supplied to out of town patients. 2. An equimolar mixture of Na2SO4 and NaHSO4 is a safe alternative which may be used to protect specimens en route to the laboratory. 3. Addition of bisulfate buffer to urine (20 g/l) reduced the pH to 2.0-3.5 (31 specimens; 24 hr urine volumes, 560-3320 ml). 4. Little change in pH was observed when buffered urine (12 specimens) was kept at 30 degrees for 14 days (initial pH 2.62 +/- 0.38 (mean +/- standard deviation); PH after 14 days, 2.59 +/- 0.48). 5. Analysis of the creatinine, 17-oxosteroids, 17-oxogenicsteroids, estrogens, pregnanediol, androsterone + etiocholanolone and estriol in urine samples acidified to pH 2-3 with HCl, and in the same samples acidified with buffer, gave results which were indistinguishable from each other. 6. Almost no change in steroid and creatinine concentrations was observed in samples of buffered urine kept for 10 days at room temperature (20-26 degrees).", "contents": "Use of a sulfate: hydrogen sulfate buffer to preserve urine for steroid analysis. 1. HCI, commonly used to preserve urine for steroid analysis, cannot safely be supplied to out of town patients. 2. An equimolar mixture of Na2SO4 and NaHSO4 is a safe alternative which may be used to protect specimens en route to the laboratory. 3. Addition of bisulfate buffer to urine (20 g/l) reduced the pH to 2.0-3.5 (31 specimens; 24 hr urine volumes, 560-3320 ml). 4. Little change in pH was observed when buffered urine (12 specimens) was kept at 30 degrees for 14 days (initial pH 2.62 +/- 0.38 (mean +/- standard deviation); PH after 14 days, 2.59 +/- 0.48). 5. Analysis of the creatinine, 17-oxosteroids, 17-oxogenicsteroids, estrogens, pregnanediol, androsterone + etiocholanolone and estriol in urine samples acidified to pH 2-3 with HCl, and in the same samples acidified with buffer, gave results which were indistinguishable from each other. 6. Almost no change in steroid and creatinine concentrations was observed in samples of buffered urine kept for 10 days at room temperature (20-26 degrees)."}
{"id": "PMID:28859", "title": "Measurement of free calcium ion in capillary blood and serum.", "content": "We describe a new calcium ion-selective electrode for measurement of the substance concentration of free calcium ion [Ca2+] in the plasma phase of whole blood and in serum at 37 degrees C. A sample volume of 50 microliter suffices to obtain simultaneous values of pH and [Ca2+]. We found the within-series analytical standard deviation for serum to be 0.013 mmol/litre (CV, 1.1%) and day-to-day precision to be 0.022 mmol/litre (CV, 1.7%). The reference interval for [Ca2+] (at pH 7.40) in serum was found to be 1.184 +/- 0.054 mmol/litre (2 SD) from measurements on sera from 121 healthy blood donors. Measurements on capillary blood from 29 healthy volunteers gave a mean (+/- 2 SD) value for [Ca2+] (at pH 7.40) of 1.22 +/- 0.072 mmol/litre.", "contents": "Measurement of free calcium ion in capillary blood and serum. We describe a new calcium ion-selective electrode for measurement of the substance concentration of free calcium ion [Ca2+] in the plasma phase of whole blood and in serum at 37 degrees C. A sample volume of 50 microliter suffices to obtain simultaneous values of pH and [Ca2+]. We found the within-series analytical standard deviation for serum to be 0.013 mmol/litre (CV, 1.1%) and day-to-day precision to be 0.022 mmol/litre (CV, 1.7%). The reference interval for [Ca2+] (at pH 7.40) in serum was found to be 1.184 +/- 0.054 mmol/litre (2 SD) from measurements on sera from 121 healthy blood donors. Measurements on capillary blood from 29 healthy volunteers gave a mean (+/- 2 SD) value for [Ca2+] (at pH 7.40) of 1.22 +/- 0.072 mmol/litre."}
{"id": "PMID:28860", "title": "An \"oncometer\" of clinical measurement of colloid osmotic pressure of plasma.", "content": "Measurement of colloid osmotic pressure complements measurements of pulmonary artery wedge pressure for assessing the risks of pulmonary edema and constitutes an increasingly important reference for purposes of guiding selection of colloid or crystalloid fluids in patients with acute cardiac disease. We describe a simple device for its routine clinical measurement. A membrane, selectively impermeable to molecules of relative molecular mass (Mr) greater than 30000, is rigidly mounted between a sample chamber and a reference chamber filled with isotonic saline. A pressure transducer measures the negative pressure developed in the reference chamber and displays it on a digital panel meter. The sensor chamber accommodates samples of 50 to 300 microliter. Equilibration is completed within 2 min. A control solution of human serum albumin (50 g/liter) is measured to confirm the accuracy of calibration of the system, with reproducible readings of 25.9 g/cm2 within one SD (equivalent to 0.4 g/cm2). Technical simplicity of operation and modest costs of disposables have made feasible the routine measurement of colloid osmotic pressure.", "contents": "An \"oncometer\" of clinical measurement of colloid osmotic pressure of plasma. Measurement of colloid osmotic pressure complements measurements of pulmonary artery wedge pressure for assessing the risks of pulmonary edema and constitutes an increasingly important reference for purposes of guiding selection of colloid or crystalloid fluids in patients with acute cardiac disease. We describe a simple device for its routine clinical measurement. A membrane, selectively impermeable to molecules of relative molecular mass (Mr) greater than 30000, is rigidly mounted between a sample chamber and a reference chamber filled with isotonic saline. A pressure transducer measures the negative pressure developed in the reference chamber and displays it on a digital panel meter. The sensor chamber accommodates samples of 50 to 300 microliter. Equilibration is completed within 2 min. A control solution of human serum albumin (50 g/liter) is measured to confirm the accuracy of calibration of the system, with reproducible readings of 25.9 g/cm2 within one SD (equivalent to 0.4 g/cm2). Technical simplicity of operation and modest costs of disposables have made feasible the routine measurement of colloid osmotic pressure."}
{"id": "PMID:28861", "title": "Quality control of measurements of pH, carbon dioxide tension, and total carbon dioxide in plasma.", "content": "We have measured total carbon dioxide in plasma with a new carbon dioxide analyzer, and compared the results with total carbon dioxide data derived from measurements of carbon dioxide tension and pH. The results agree sufficiently well to demonstrate that the new instrument provides a simple, efficient procedure for monitoring the precision and accuracy of pH, carbon dioxide tension, or total carbon dioxide in plasma.", "contents": "Quality control of measurements of pH, carbon dioxide tension, and total carbon dioxide in plasma. We have measured total carbon dioxide in plasma with a new carbon dioxide analyzer, and compared the results with total carbon dioxide data derived from measurements of carbon dioxide tension and pH. The results agree sufficiently well to demonstrate that the new instrument provides a simple, efficient procedure for monitoring the precision and accuracy of pH, carbon dioxide tension, or total carbon dioxide in plasma."}
{"id": "PMID:28865", "title": "Gaucher's disease. Factors affecting the 4-methylum-belliferyl-beta-D-glucosidase activity of cultured skin fibroblasts.", "content": "Phosphate-buffered saline was found to inhibit acid beta-glucosidase activity of cultured cells. This effect was attributable to both the pH and the chloride content of the phosphate-buffered saline. Washing the cells in sucrose (0.25M) to remove residual phosphate-buffered saline effectively eliminated this inhibition.", "contents": "Gaucher's disease. Factors affecting the 4-methylum-belliferyl-beta-D-glucosidase activity of cultured skin fibroblasts. Phosphate-buffered saline was found to inhibit acid beta-glucosidase activity of cultured cells. This effect was attributable to both the pH and the chloride content of the phosphate-buffered saline. Washing the cells in sucrose (0.25M) to remove residual phosphate-buffered saline effectively eliminated this inhibition."}
{"id": "PMID:28868", "title": "Doses and dosage intervals of drugs--clinical practice and pharmacokinetic principles.", "content": "Outpatient prescriptions dispensed to 17,000 individuals in the county of J\u00e4mtland, Sweden, have been analyzed with regard to doses and dosage schedules. Two groups of drugs were studied; one group with marked interindividual variability in metabolism (antidepressants, beta receptor blockers, and phenytoin), the other group excreted unchanged in the urine (digoxin, nitrofurantoin, sulfonamides, and tetracycline). A 25-fold-15-fold variability in daily doses was found for amitriptyline and nortiptyline, respectively. Four-fifths of the prescriptions were for doses between 30 and 75 mg, making the mean dose remarkably low-58 and 48 mg, respectively. The variability in doses was higher for the beta receptor blockers propranolol and alprenolol. Daily doses of phenytoin varied between 0.1 and 0.6 gm, 93% of the doses falling between 0.2 and 0.4 gm. Generally, doses of sulfonamides and nitrofurantoin prescribed to children were correctly reduced. In the elderly the doses of these drugs and tetracycline and digoxin were only moderately reduced in discrepancy with the physiologic impairment of kidney function. The clinical significance of these findings has not been evaluated. The effect of drug information programs on dosage intervals prescribed for procainamide, phenytoin, and beta receptor blocking drugs is demonstrated. It is suggested that more emphasis be given to general pharmacokinetic principles in drug information programs.", "contents": "Doses and dosage intervals of drugs--clinical practice and pharmacokinetic principles. Outpatient prescriptions dispensed to 17,000 individuals in the county of J\u00e4mtland, Sweden, have been analyzed with regard to doses and dosage schedules. Two groups of drugs were studied; one group with marked interindividual variability in metabolism (antidepressants, beta receptor blockers, and phenytoin), the other group excreted unchanged in the urine (digoxin, nitrofurantoin, sulfonamides, and tetracycline). A 25-fold-15-fold variability in daily doses was found for amitriptyline and nortiptyline, respectively. Four-fifths of the prescriptions were for doses between 30 and 75 mg, making the mean dose remarkably low-58 and 48 mg, respectively. The variability in doses was higher for the beta receptor blockers propranolol and alprenolol. Daily doses of phenytoin varied between 0.1 and 0.6 gm, 93% of the doses falling between 0.2 and 0.4 gm. Generally, doses of sulfonamides and nitrofurantoin prescribed to children were correctly reduced. In the elderly the doses of these drugs and tetracycline and digoxin were only moderately reduced in discrepancy with the physiologic impairment of kidney function. The clinical significance of these findings has not been evaluated. The effect of drug information programs on dosage intervals prescribed for procainamide, phenytoin, and beta receptor blocking drugs is demonstrated. It is suggested that more emphasis be given to general pharmacokinetic principles in drug information programs."}
{"id": "PMID:28870", "title": "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide.", "content": "Ten healthy volunteers ingested single 15-mg doses of clorazepate dipotassium (CZP) with 60 ml of water, or with 60 ml of magnesium aluminum hydroxide (Maalox), on two occasions in a randomized, two-way crossover study. Plasma concentrations of desmethyldiazepam (DMDZ) were determined in multiple samples drawn during 48 hr after each dose. Mean kinetic variables for DMDZ in CZP-water and CZP-magnesium aluminum hydroxide treatment conditions, respectively, were: peak measured concentration, 273 and 188 ng/ml (p 0.001); time of peak concentration, 1.8 and 2.8 hr after dose (p less than 0.01); apparent absorption half-life, 14.8 and 30.7 min (p less than 0.02); area under the 48-hr plasma concentration curve, 6,028 and 5,433 ng/ml X hr (p less than 0.02). Self-rated sensations of feedling \"spacey,\" \"thinking slowed down,\" and of generalized sedation, were reported with both treatment conditions, but these subjective effects occurred earlier and were more profound when CZP was taken with water as opposed to magnesium aluminum hydroxide. Thus administration of single doses of CZP with usual doses of a commonly prescribed antacid reduces the rate and extent of appearance in blood of DMDZ (the compound responsible for clinical activity) and attenuates self-rated clinical effects.", "contents": "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide. Ten healthy volunteers ingested single 15-mg doses of clorazepate dipotassium (CZP) with 60 ml of water, or with 60 ml of magnesium aluminum hydroxide (Maalox), on two occasions in a randomized, two-way crossover study. Plasma concentrations of desmethyldiazepam (DMDZ) were determined in multiple samples drawn during 48 hr after each dose. Mean kinetic variables for DMDZ in CZP-water and CZP-magnesium aluminum hydroxide treatment conditions, respectively, were: peak measured concentration, 273 and 188 ng/ml (p 0.001); time of peak concentration, 1.8 and 2.8 hr after dose (p less than 0.01); apparent absorption half-life, 14.8 and 30.7 min (p less than 0.02); area under the 48-hr plasma concentration curve, 6,028 and 5,433 ng/ml X hr (p less than 0.02). Self-rated sensations of feedling \"spacey,\" \"thinking slowed down,\" and of generalized sedation, were reported with both treatment conditions, but these subjective effects occurred earlier and were more profound when CZP was taken with water as opposed to magnesium aluminum hydroxide. Thus administration of single doses of CZP with usual doses of a commonly prescribed antacid reduces the rate and extent of appearance in blood of DMDZ (the compound responsible for clinical activity) and attenuates self-rated clinical effects."}
{"id": "PMID:28875", "title": "Abnormal sodium transport in leucocytes from patients with essential hypertension and the effect of treatment.", "content": "1. In seventeen patients with untreated essential hypertension the sodium and water contents of leucocytes were significantly increased, whereas the rate constant for ouabain-sensitive sodium efflux was significantly reduced. 2. These abnormalities were not found in fourteen other patients with well-controlled hypertension. 3. Preliminary observations in accelerated hypertension suggest a different pattern of abnormality in leucocyte sodium metabolism.", "contents": "Abnormal sodium transport in leucocytes from patients with essential hypertension and the effect of treatment. 1. In seventeen patients with untreated essential hypertension the sodium and water contents of leucocytes were significantly increased, whereas the rate constant for ouabain-sensitive sodium efflux was significantly reduced. 2. These abnormalities were not found in fourteen other patients with well-controlled hypertension. 3. Preliminary observations in accelerated hypertension suggest a different pattern of abnormality in leucocyte sodium metabolism."}
{"id": "PMID:28876", "title": "Effect of pyratrione (a tyrosine hydroxylase inhibitor) in essential hypertension.", "content": "1. A clinical study of pyratrione, a tyrosine hydroxylase inhibitor, has been carried out in essential hypertension. 2. Out of thirty-nine patients who received pyratrione, twenty-eight showed a significant decrease in blood pressure.", "contents": "Effect of pyratrione (a tyrosine hydroxylase inhibitor) in essential hypertension. 1. A clinical study of pyratrione, a tyrosine hydroxylase inhibitor, has been carried out in essential hypertension. 2. Out of thirty-nine patients who received pyratrione, twenty-eight showed a significant decrease in blood pressure."}
{"id": "PMID:28878", "title": "The brain as a possible site for the cardiovascular effects of beta-adrenoceptor blocking agents in cats.", "content": "1. DL-Propranolol, L-propranolol, DL-alprenolol, pindolol (LB46), practolol, ICI 66082, sotalol and oxprenolol all produced prolonged falls in blood pressure and heart rate after intracerebroventricular administration in conscious normotensive cats. 2. Transient initial pressor responses and tachycardias were observed after intracerebroventricular infusions of all the beta-adrenoceptor antagonists used, except ICI 66082. 3. D-Propranolol, D-alphrenolol, procaine and lignocaine all produced initial increases in blood pressure and heart rate but did not subsequently cause any reduction in either blood pressure or heart rate. 4. The time of maximum hypotension and bradycardia after intracerebroventricular infusion of beta-adrenoceptor antagonists coincided with the maximum inhibition of the centrally mediated tachycardia observed after intracerebroventricular isoprenaline.", "contents": "The brain as a possible site for the cardiovascular effects of beta-adrenoceptor blocking agents in cats. 1. DL-Propranolol, L-propranolol, DL-alprenolol, pindolol (LB46), practolol, ICI 66082, sotalol and oxprenolol all produced prolonged falls in blood pressure and heart rate after intracerebroventricular administration in conscious normotensive cats. 2. Transient initial pressor responses and tachycardias were observed after intracerebroventricular infusions of all the beta-adrenoceptor antagonists used, except ICI 66082. 3. D-Propranolol, D-alphrenolol, procaine and lignocaine all produced initial increases in blood pressure and heart rate but did not subsequently cause any reduction in either blood pressure or heart rate. 4. The time of maximum hypotension and bradycardia after intracerebroventricular infusion of beta-adrenoceptor antagonists coincided with the maximum inhibition of the centrally mediated tachycardia observed after intracerebroventricular isoprenaline."}
{"id": "PMID:28880", "title": "beta-Adrenergic receptors and renin release: studies with beta-adrenoreceptor-blocking agents in the conscious rabbit.", "content": "1. Plasma renin activity (PRA) and mean blood pressure were studied in conscious rabbits infused with beta-adrenoreceptor antagonists. 2. Oxprenolol and DL-propranolol each significantly reduced PRA and blood pressure, but prindolol, which had a strong blood pressure-lowering effect, increased PRA. 3. When prindolol was given to animals in which PRA and blood pressure had been reduced by DL-propranolol, PRA returned to control values but blood pressure remained low. Thus the increase in PRA caused by prindolol is not mediated by hypotension. These findings, together with the observation that compound H35/25 reduced PRA without altering blood pressure, suggest that the effects of the beta-adrenoreceptor-blocking drugs on blood pressure are unrelated to their effects on renin release. 4. Studies with D-propranolol and with blocking agents with either beta-1 or beta-2 specificity indicated that the effects of beta-adrenoreceptor blockade on renin are directly dependent upon their action on beta-adrenergic receptors, probably of the beta-2 type.", "contents": "beta-Adrenergic receptors and renin release: studies with beta-adrenoreceptor-blocking agents in the conscious rabbit. 1. Plasma renin activity (PRA) and mean blood pressure were studied in conscious rabbits infused with beta-adrenoreceptor antagonists. 2. Oxprenolol and DL-propranolol each significantly reduced PRA and blood pressure, but prindolol, which had a strong blood pressure-lowering effect, increased PRA. 3. When prindolol was given to animals in which PRA and blood pressure had been reduced by DL-propranolol, PRA returned to control values but blood pressure remained low. Thus the increase in PRA caused by prindolol is not mediated by hypotension. These findings, together with the observation that compound H35/25 reduced PRA without altering blood pressure, suggest that the effects of the beta-adrenoreceptor-blocking drugs on blood pressure are unrelated to their effects on renin release. 4. Studies with D-propranolol and with blocking agents with either beta-1 or beta-2 specificity indicated that the effects of beta-adrenoreceptor blockade on renin are directly dependent upon their action on beta-adrenergic receptors, probably of the beta-2 type."}
{"id": "PMID:28897", "title": "Effect of drugs on the stimulation threshold of the human heart.", "content": "Clinical measurements were made of the effects of various drugs on the stimulation threshold of human heart [right ventricle]. Of antiarrhythmic drugs, a marked and prolonged elevation of the stimulation threshold was produced by procainamide, quinidine, and aimaline. Relatively short-lasting elevation was elicited by local anaesthetics [trimecaine, lidocaine]. Beta-blockers were little effective. No detectable effect on the stimulation threshold was produced by phenytoin and digitalis glucosides from the group of antiarrhythmics. The deepest and most prolonged depression of the stimulation threshold was achieved with anabolics [nandrolone phenylpropionate, nandrolone decanoate] and with high doses of prednisone and of 6-methylprednisolone sodium succinate. Hydrocortisone was ineffective. A slight and brief depression was produced by atrophine. The effects of sympathomimetics were complicated: at stimulation with short pulses the threshold was always raised. At stimulation with long pulses the effects were variable, mostly biphasic [occasionally triphasic]: a transitory depression of the stimulation threshold was followed by a marked elevation. The I-t curve's slope altered. In exit block, sympathomimetics are indicated because of their chronotropic effect, not because of their questionable effect on the stimulation threshold. A number of drugs, often administered to stimulated patients, produced no effect on the stimulation threshold: antibiotics, nitrites, purine compounds, opiates, and others.", "contents": "Effect of drugs on the stimulation threshold of the human heart. Clinical measurements were made of the effects of various drugs on the stimulation threshold of human heart [right ventricle]. Of antiarrhythmic drugs, a marked and prolonged elevation of the stimulation threshold was produced by procainamide, quinidine, and aimaline. Relatively short-lasting elevation was elicited by local anaesthetics [trimecaine, lidocaine]. Beta-blockers were little effective. No detectable effect on the stimulation threshold was produced by phenytoin and digitalis glucosides from the group of antiarrhythmics. The deepest and most prolonged depression of the stimulation threshold was achieved with anabolics [nandrolone phenylpropionate, nandrolone decanoate] and with high doses of prednisone and of 6-methylprednisolone sodium succinate. Hydrocortisone was ineffective. A slight and brief depression was produced by atrophine. The effects of sympathomimetics were complicated: at stimulation with short pulses the threshold was always raised. At stimulation with long pulses the effects were variable, mostly biphasic [occasionally triphasic]: a transitory depression of the stimulation threshold was followed by a marked elevation. The I-t curve's slope altered. In exit block, sympathomimetics are indicated because of their chronotropic effect, not because of their questionable effect on the stimulation threshold. A number of drugs, often administered to stimulated patients, produced no effect on the stimulation threshold: antibiotics, nitrites, purine compounds, opiates, and others."}
{"id": "PMID:28898", "title": "What are the driving forces for the proximal tubular H+ and Ca++ transport? The electrochemical gradient for Na+ and/or ATP.", "content": "The H+ ion secretion in the proximal tubule as revealed by the reabsorption of the glycodiazine buffer vanishes when the ambient solutions are sodium-free. The same holds for other Na+-dependent transport processes such as Ca++, phosphate, glucose and amino acid reabsorption. If Na+ transport is blocked by ouabain the latter transport processes are abolished, the secretion of H+ ions, however, remains unchanged suggesting H+ to be not exclusively driven by active Na+ transport. These observations agree with electrical measurements which show an electrogenic component of H+ secretion to exist in rat proximal tubule. In experiments with isolated membrane vesicles an electroneutral Na+/H+-exchange mechanism could be demonstrated in the brush border membrane and an ATP-driven Ca++ pumpt as well as Na+-Ca++ countertransport in the baso-lateral cell membrane. These data suggest that both, the Na+ gradient and ATP, are used to drive H+ ion secretion across the luminal brush border and Ca++ reabsorption across the baso-lateral cell side. The biochemical nature of the various systems and their relative importance for the transepithelial ion movement remain to be elucidated.", "contents": "What are the driving forces for the proximal tubular H+ and Ca++ transport? The electrochemical gradient for Na+ and/or ATP. The H+ ion secretion in the proximal tubule as revealed by the reabsorption of the glycodiazine buffer vanishes when the ambient solutions are sodium-free. The same holds for other Na+-dependent transport processes such as Ca++, phosphate, glucose and amino acid reabsorption. If Na+ transport is blocked by ouabain the latter transport processes are abolished, the secretion of H+ ions, however, remains unchanged suggesting H+ to be not exclusively driven by active Na+ transport. These observations agree with electrical measurements which show an electrogenic component of H+ secretion to exist in rat proximal tubule. In experiments with isolated membrane vesicles an electroneutral Na+/H+-exchange mechanism could be demonstrated in the brush border membrane and an ATP-driven Ca++ pumpt as well as Na+-Ca++ countertransport in the baso-lateral cell membrane. These data suggest that both, the Na+ gradient and ATP, are used to drive H+ ion secretion across the luminal brush border and Ca++ reabsorption across the baso-lateral cell side. The biochemical nature of the various systems and their relative importance for the transepithelial ion movement remain to be elucidated."}
{"id": "PMID:28899", "title": "Cytoplasmic gamma-glutamyltransferase: isolation, product formation and physiological role.", "content": "These results establish the existence of a cytoplasmic glutaminase-gamma-glutamyltransferase enzyme as a distinct entity. Its products are ammonia and activated glutamate. Ammonia liberation is obligatory to the utilization of the amide bond energy in forming gamma-glutamyl-PO4. This activated glutamate can then be utilized in the gamma-glutamyl cycle for the synthesis of gamma-glutamylcysteine. The cytoplasmic glutamine utilizing pathway is closely coupled to gamma-glutamyl cycl activity: loading the cycle stimulates increased renal glutamine uptake into this pathway. Consequently, the pathway, stimulated by elevated ADP levels, appears to function as an auxilary source of gamma-glutamyl moieties for the gamma-glutamyl cycle. Although insignificant compared to the mitochondrial pathway's contribution to ammonia production in metabolic acidosis, it is highly significant from the perspective of the Unitary Hypothesis. The existence of this dual system allows the demonstration of a shift in glutamine utilization from predominant cytoplasmic to overwhelming mitochondrial glutamine utilization in metabolic acidosis corresponding to a rise in the NH3/gln ratio from 1.2 to 1.9 and a quantitative recovery of gln carbon as CO2 and glucose. The fact that this shift in pathways is induced by acidosis (through adrenosteroids) and that it represents a 10 to 20 fold activation of the mitochondrial pathway is completely consistent with a glucocorticoid mediated glutamine permeability increase of the inner mitochondrial membrane.", "contents": "Cytoplasmic gamma-glutamyltransferase: isolation, product formation and physiological role. These results establish the existence of a cytoplasmic glutaminase-gamma-glutamyltransferase enzyme as a distinct entity. Its products are ammonia and activated glutamate. Ammonia liberation is obligatory to the utilization of the amide bond energy in forming gamma-glutamyl-PO4. This activated glutamate can then be utilized in the gamma-glutamyl cycle for the synthesis of gamma-glutamylcysteine. The cytoplasmic glutamine utilizing pathway is closely coupled to gamma-glutamyl cycl activity: loading the cycle stimulates increased renal glutamine uptake into this pathway. Consequently, the pathway, stimulated by elevated ADP levels, appears to function as an auxilary source of gamma-glutamyl moieties for the gamma-glutamyl cycle. Although insignificant compared to the mitochondrial pathway's contribution to ammonia production in metabolic acidosis, it is highly significant from the perspective of the Unitary Hypothesis. The existence of this dual system allows the demonstration of a shift in glutamine utilization from predominant cytoplasmic to overwhelming mitochondrial glutamine utilization in metabolic acidosis corresponding to a rise in the NH3/gln ratio from 1.2 to 1.9 and a quantitative recovery of gln carbon as CO2 and glucose. The fact that this shift in pathways is induced by acidosis (through adrenosteroids) and that it represents a 10 to 20 fold activation of the mitochondrial pathway is completely consistent with a glucocorticoid mediated glutamine permeability increase of the inner mitochondrial membrane."}
{"id": "PMID:28902", "title": "alpha-Ketoglutarate regulation of glutamine transport and deamidation in renal mitochondria.", "content": "alpha-Ketoglutarate (KG) is a potent inhibitor of renal mitochondrial glutamine transport and deamidation at physiological concentrations. The concentration-inhibition relationship observed between KG and mitochondrial glutamine transport and deamidation indicates that changes in renal KG concentration occurring during alterations in acid-base balance would have significant effects on mitochondrial ammonia production in vivo. A rapid-mixing, rapid-filtration method was developed to measure the effects of KG on initial rates of mitochondrial glutamine transport. Transport was linear for only a few seconds and approached steady-state conditions by 30 seconds. KG (0.3 mM) raised the glutamine transport Km approximately two-fold. We propose that KG may play a major regulatory role in the early adaptation of renal ammonia production to acidosis.", "contents": "alpha-Ketoglutarate regulation of glutamine transport and deamidation in renal mitochondria. alpha-Ketoglutarate (KG) is a potent inhibitor of renal mitochondrial glutamine transport and deamidation at physiological concentrations. The concentration-inhibition relationship observed between KG and mitochondrial glutamine transport and deamidation indicates that changes in renal KG concentration occurring during alterations in acid-base balance would have significant effects on mitochondrial ammonia production in vivo. A rapid-mixing, rapid-filtration method was developed to measure the effects of KG on initial rates of mitochondrial glutamine transport. Transport was linear for only a few seconds and approached steady-state conditions by 30 seconds. KG (0.3 mM) raised the glutamine transport Km approximately two-fold. We propose that KG may play a major regulatory role in the early adaptation of renal ammonia production to acidosis."}
{"id": "PMID:28906", "title": "Neuropharmacological aspects of the neural control of prolactin secretion.", "content": "The use of neuropharmacological agents in neuroendocrine studies has had a significant impact on our knowledge about the neurotransmitter systems that are involved in the control of prolactin secretion. Selective drugs have played a key role in the identification of the dopaminergic inhibitory and serotonergic stimulatory influences. With the development of additional specific neuropharmacological agents in the future, we can expect to gain a better understanding of the complex neural interrelationships involved in the control of anterior pituitary hormone secretion. In view of what we already know about the neurotransmitters involved in the control of prolactin release, a tentative neuronal configuration can be proposed. The following neuronal network most probably does not include several components that may be shown by future studies to be involved in prolactin control, but it does represent a possible functional network based on what knowledge is at the present time (Fig. 4).", "contents": "Neuropharmacological aspects of the neural control of prolactin secretion. The use of neuropharmacological agents in neuroendocrine studies has had a significant impact on our knowledge about the neurotransmitter systems that are involved in the control of prolactin secretion. Selective drugs have played a key role in the identification of the dopaminergic inhibitory and serotonergic stimulatory influences. With the development of additional specific neuropharmacological agents in the future, we can expect to gain a better understanding of the complex neural interrelationships involved in the control of anterior pituitary hormone secretion. In view of what we already know about the neurotransmitters involved in the control of prolactin release, a tentative neuronal configuration can be proposed. The following neuronal network most probably does not include several components that may be shown by future studies to be involved in prolactin control, but it does represent a possible functional network based on what knowledge is at the present time (Fig. 4)."}
{"id": "PMID:28903", "title": "Effects of maleate on CoA metabolism in rat kidney.", "content": "CoA transfer from acetoacetyl-CoA to maleate catalyzed by purified CoA transferase was studied. The thioester product of the reaction undergoes further chemical transformations and the final product appeared to be stable CoA derivative showing neither free SH group nor hydrolyzable thio-acyl bond. Similar product was obtained as the result of the reaction of addition of CoA to the double bond of maleic anhydride. This was confirmed by DEAE-chromatography. The decrease of free CoA and acid soluble acyl-CoA in kidney mitochondria respiring in the presence of maleate or in the kidney of maleate-treated rats occured without appreciable changes in acid insoluble acyl-CoA derivatives. As the result substantial loss of total content of CoA was found. The data indicate that maleate binds and removes CoA in the form of stable and metabolically inert compound.", "contents": "Effects of maleate on CoA metabolism in rat kidney. CoA transfer from acetoacetyl-CoA to maleate catalyzed by purified CoA transferase was studied. The thioester product of the reaction undergoes further chemical transformations and the final product appeared to be stable CoA derivative showing neither free SH group nor hydrolyzable thio-acyl bond. Similar product was obtained as the result of the reaction of addition of CoA to the double bond of maleic anhydride. This was confirmed by DEAE-chromatography. The decrease of free CoA and acid soluble acyl-CoA in kidney mitochondria respiring in the presence of maleate or in the kidney of maleate-treated rats occured without appreciable changes in acid insoluble acyl-CoA derivatives. As the result substantial loss of total content of CoA was found. The data indicate that maleate binds and removes CoA in the form of stable and metabolically inert compound."}
{"id": "PMID:28904", "title": "Metabolic changes induced by acute phosphate loading in acutely thyroparathyroidectomized rats.", "content": "Phosphate loading in acutely thyroparathyroidectomized rats is followed by a decline of phosphate reabsorption. In addition, a mixed respiratory and metabolic alkalosis and hypocalcemia develop. Normalization of plasma calcium concentration, unlike the reversal of the alkalosis, prevents the fall in phosphate reabsorption.", "contents": "Metabolic changes induced by acute phosphate loading in acutely thyroparathyroidectomized rats. Phosphate loading in acutely thyroparathyroidectomized rats is followed by a decline of phosphate reabsorption. In addition, a mixed respiratory and metabolic alkalosis and hypocalcemia develop. Normalization of plasma calcium concentration, unlike the reversal of the alkalosis, prevents the fall in phosphate reabsorption."}
{"id": "PMID:28905", "title": "Biochemical, immunological and ultrastructural studies on brush-border membranes of human kidney.", "content": "Brush border (BB) membranes, isolated from human kidney cortex by density gradient centrifugation, revealed a distinct pattern of structural proteins as could be shown by bio- and immunochemical studies. Marker enzymes such as gamma-glutamyltranspeptidase (GGTP) and alanine-aminopeptidase (AAP) were characterized as extrinsic; alkaline phosphatase (AP) was characterized as an integral constituent of the BB membrane. The surface of the BB membranes exhibited numerous 5 nm particles bound through a linear component to the peripheral BB matrix (negative staining). Increase of AAP and GGTP (30%) activity in the supernatant after proteolytic treatment of BB fragments paralleled selective release of these constituents from the membranes. The surface components were found to be part of BB concanavalin A and wheat germ agglutinin receptor sites. Labelled antisera directed against surface glycoprotein fractions gave a specific immuno fluorescence staining of only the luminal plasma-membrane from the proximal tubule epithelia.", "contents": "Biochemical, immunological and ultrastructural studies on brush-border membranes of human kidney. Brush border (BB) membranes, isolated from human kidney cortex by density gradient centrifugation, revealed a distinct pattern of structural proteins as could be shown by bio- and immunochemical studies. Marker enzymes such as gamma-glutamyltranspeptidase (GGTP) and alanine-aminopeptidase (AAP) were characterized as extrinsic; alkaline phosphatase (AP) was characterized as an integral constituent of the BB membrane. The surface of the BB membranes exhibited numerous 5 nm particles bound through a linear component to the peripheral BB matrix (negative staining). Increase of AAP and GGTP (30%) activity in the supernatant after proteolytic treatment of BB fragments paralleled selective release of these constituents from the membranes. The surface components were found to be part of BB concanavalin A and wheat germ agglutinin receptor sites. Labelled antisera directed against surface glycoprotein fractions gave a specific immuno fluorescence staining of only the luminal plasma-membrane from the proximal tubule epithelia."}
{"id": "PMID:28913", "title": "[Successful therapy of a severe dextran incident using histamin H1- and H2-receptor blockaders].", "content": "A case of a severe systemic anaphylactoid reaction is reported in a patient treated with dextran 60 to prevent venous thrombosis. Significant improvement of clinical symptoms occurred after the usual treatment of such incidents with corticosteroids, histamine H1 receptor antagonists, and plasma substitutes was supplemented with a histamine H2 receptor antagonist. We would therefore like to recommend that for such cases a histamine H2 receptor antagonist should be given in addition to the usual medication with corticosteroids and histamine H1 receptor antagonists. However, the value of complete histamine antagonism in these rather rare occurrences, can only be determined after furtherexperience has been gained.", "contents": "[Successful therapy of a severe dextran incident using histamin H1- and H2-receptor blockaders]. A case of a severe systemic anaphylactoid reaction is reported in a patient treated with dextran 60 to prevent venous thrombosis. Significant improvement of clinical symptoms occurred after the usual treatment of such incidents with corticosteroids, histamine H1 receptor antagonists, and plasma substitutes was supplemented with a histamine H2 receptor antagonist. We would therefore like to recommend that for such cases a histamine H2 receptor antagonist should be given in addition to the usual medication with corticosteroids and histamine H1 receptor antagonists. However, the value of complete histamine antagonism in these rather rare occurrences, can only be determined after furtherexperience has been gained."}
{"id": "PMID:28915", "title": "The biotransformation of p-xylene to a toxic aldehyde.", "content": "Rats given a single ip injection of p-xylene suffered 65% loss of pulmonary microsomal p-xylene hydroxylase activity. The activity was protected by pretreating the rats with phenobarbital, which increased hepatic p-xylene hydroxylase and cytosolic aldehyde dehydrogenase activities, but had no effect on alcohol dehydrogenase activity in hepatic cytosol. Pretreatment of rats with pyrazole caused a 60% inhibition of liver alcohol dehydrogenase but had no effect on liver aldehyde dehydrogenase activity. This treatment partially protected the pulmonary microsomal p-xylene hydroxylase from inactivation by p-xylene. Experiments in vitro showed that inactivation of cytochrome P-450 by p-xylene required the metabolic conversion of p-xylene to p-tolualdehyde. The reactive intermediate (p-tolualdehyde) required the presence of NADPH to carry out the inactivation. Inasmuch as lung tissues cannot form p-tolualdehyde (because of the low activity of p-methylbenzyl alcohol dehydrogenase), it is assumed that the inactivation of lung enzymes in vivo following exposure to p-xylene was due to the aldehyde intermediate which is formed in the liver and transported to the lung.", "contents": "The biotransformation of p-xylene to a toxic aldehyde. Rats given a single ip injection of p-xylene suffered 65% loss of pulmonary microsomal p-xylene hydroxylase activity. The activity was protected by pretreating the rats with phenobarbital, which increased hepatic p-xylene hydroxylase and cytosolic aldehyde dehydrogenase activities, but had no effect on alcohol dehydrogenase activity in hepatic cytosol. Pretreatment of rats with pyrazole caused a 60% inhibition of liver alcohol dehydrogenase but had no effect on liver aldehyde dehydrogenase activity. This treatment partially protected the pulmonary microsomal p-xylene hydroxylase from inactivation by p-xylene. Experiments in vitro showed that inactivation of cytochrome P-450 by p-xylene required the metabolic conversion of p-xylene to p-tolualdehyde. The reactive intermediate (p-tolualdehyde) required the presence of NADPH to carry out the inactivation. Inasmuch as lung tissues cannot form p-tolualdehyde (because of the low activity of p-methylbenzyl alcohol dehydrogenase), it is assumed that the inactivation of lung enzymes in vivo following exposure to p-xylene was due to the aldehyde intermediate which is formed in the liver and transported to the lung."}
{"id": "PMID:28916", "title": "Microsomal metabolism of cyclohexene. Hydroxylation in the allylic position.", "content": "Hydroxylation of cyclohexene at the allylic position has been shown to occur in hepatic microsomes and 9000 g supernatant fractions of rats and rabbits. The formation of the product, 2-cyclohexen-1-ol, requires the presence of a NADPH-generating system, is inhibited by CO, metyrapone, and SKF 525-A, and is induced by pretreatment with phenobarbital. A small amount of 2-cyclohexen-1-one is also formed in preparations from phenobarbital-pretreated rats. No 2-cyclohexen-1-ol could be detected in the beta-glucuronidase-hydrolyzed urine of rats given cyclohexene orally; however, these rats excreted a small quantity of 2-cyclohexen-1-one.", "contents": "Microsomal metabolism of cyclohexene. Hydroxylation in the allylic position. Hydroxylation of cyclohexene at the allylic position has been shown to occur in hepatic microsomes and 9000 g supernatant fractions of rats and rabbits. The formation of the product, 2-cyclohexen-1-ol, requires the presence of a NADPH-generating system, is inhibited by CO, metyrapone, and SKF 525-A, and is induced by pretreatment with phenobarbital. A small amount of 2-cyclohexen-1-one is also formed in preparations from phenobarbital-pretreated rats. No 2-cyclohexen-1-ol could be detected in the beta-glucuronidase-hydrolyzed urine of rats given cyclohexene orally; however, these rats excreted a small quantity of 2-cyclohexen-1-one."}
{"id": "PMID:28918", "title": "Synthesis and characterization of glucuronides of 5'-hydroxy-delta9-tetrahydrocannabinol and 11-hydroxy-delta9-tetrahydrocannabinol.", "content": "Glucuronides of two metabolites of delta9-tetrahydrocannabinol, 11-hydroxy-delta9-THC and 5'-hydroxy-delta9-THC, have been synthesized and characterized. Two isomeric monoglucuronides were isolated from the incubation of each metabolite with UDP-glucuronyltransferase immobilized on beaded Sepharose. The structures of these conjugates were assigned primarily on the basis of combined gas chromatography-mass spectrometry.", "contents": "Synthesis and characterization of glucuronides of 5'-hydroxy-delta9-tetrahydrocannabinol and 11-hydroxy-delta9-tetrahydrocannabinol. Glucuronides of two metabolites of delta9-tetrahydrocannabinol, 11-hydroxy-delta9-THC and 5'-hydroxy-delta9-THC, have been synthesized and characterized. Two isomeric monoglucuronides were isolated from the incubation of each metabolite with UDP-glucuronyltransferase immobilized on beaded Sepharose. The structures of these conjugates were assigned primarily on the basis of combined gas chromatography-mass spectrometry."}
{"id": "PMID:28919", "title": "In vitro metabolism of phenylacetone, phenyl-2-butanone, and 3-methyl-1-phenyl-2-butanone by rabbit liver preparations.", "content": "Phenylacetone, phenyl-2-butanone, and 3-methyl-1-phenyl-2-butanone were incubated with rabbit liver 9000g supernatant fraction for 30 and 60 min to yield primarily the alcohols, plus small amounts of 1,2-glycols and ketols (2-one-1-ols). Phenylacetone incubations produced small amounts of benzoic acid, which was confirmed as a true metabolite by incubation of 2H5 (phenyl-labeled) phenylacetone and corresponding recovery of phenyl-labeled benzoic acid. No benzoic acid was detectable from incubations of phenyl-2-butanone and 3-methyl-1-phenyl-2-butanone. 3-Methyl-1-phenyl-2-butanone yielded eight metabolites in addition to the corresponding alcohol, and structures are proposed for some of these metabolic products.", "contents": "In vitro metabolism of phenylacetone, phenyl-2-butanone, and 3-methyl-1-phenyl-2-butanone by rabbit liver preparations. Phenylacetone, phenyl-2-butanone, and 3-methyl-1-phenyl-2-butanone were incubated with rabbit liver 9000g supernatant fraction for 30 and 60 min to yield primarily the alcohols, plus small amounts of 1,2-glycols and ketols (2-one-1-ols). Phenylacetone incubations produced small amounts of benzoic acid, which was confirmed as a true metabolite by incubation of 2H5 (phenyl-labeled) phenylacetone and corresponding recovery of phenyl-labeled benzoic acid. No benzoic acid was detectable from incubations of phenyl-2-butanone and 3-methyl-1-phenyl-2-butanone. 3-Methyl-1-phenyl-2-butanone yielded eight metabolites in addition to the corresponding alcohol, and structures are proposed for some of these metabolic products."}
{"id": "PMID:28920", "title": "Reductive metabolism of nitrofurantoin in the rat.", "content": "The reductive metabolism of nitrofurantoin under anaerobic conditions was characterized in various tissues from control, germ-free, and germ-free acclimatized rats. Nitrofurantoin metabolism was highest in homogenates of cecum and colon contents of germ-free acclimatized and control rats, but was absent from those of germ-free animals. Appreciable levels of activity were also present in homogenates of liver and of small intestine walls with lesser rates of metabolism observed in kidney homogenates. The major metabolite of nitrofurantoin, which was isolated and purified by high-pressure liquid chromatography, was identified as 1-[[(3-cyano-1-oxopropyl)-methylene]amino]-2,4-imidazolidinedione. A second, minor metabolite with high-pressure liquid chromatography and ultraviolet absorption characteristics similar to those of 1-[[(5-amino-2-furanyl)methylene]amino]-2,4-imidazolidinedione (aminofurantoin) was detected in cecum and colon contents.", "contents": "Reductive metabolism of nitrofurantoin in the rat. The reductive metabolism of nitrofurantoin under anaerobic conditions was characterized in various tissues from control, germ-free, and germ-free acclimatized rats. Nitrofurantoin metabolism was highest in homogenates of cecum and colon contents of germ-free acclimatized and control rats, but was absent from those of germ-free animals. Appreciable levels of activity were also present in homogenates of liver and of small intestine walls with lesser rates of metabolism observed in kidney homogenates. The major metabolite of nitrofurantoin, which was isolated and purified by high-pressure liquid chromatography, was identified as 1-[[(3-cyano-1-oxopropyl)-methylene]amino]-2,4-imidazolidinedione. A second, minor metabolite with high-pressure liquid chromatography and ultraviolet absorption characteristics similar to those of 1-[[(5-amino-2-furanyl)methylene]amino]-2,4-imidazolidinedione (aminofurantoin) was detected in cecum and colon contents."}
{"id": "PMID:28921", "title": "Differential effects of Walker 256 carcinosarcoma cells growing subcutaneously, intramuscularly, or intraperitoneally on hepatic microsomal mixed-function oxygenase activity.", "content": "Walker 256 rat carcinosarcoma cells growing as solid subcutaneous or intramuscular tumors depressed hepatic microsomal mixed-function oxygenase activity to less than 20% of control activity, but the same tumor cells growing as free ascites cells in the peritoneal cavity did not. Necrosis of the core area of solid tumors was observed. Tumor cells may release a substance that depresses hepatic microsomal mixed-function oxygenase activity only upon their death.", "contents": "Differential effects of Walker 256 carcinosarcoma cells growing subcutaneously, intramuscularly, or intraperitoneally on hepatic microsomal mixed-function oxygenase activity. Walker 256 rat carcinosarcoma cells growing as solid subcutaneous or intramuscular tumors depressed hepatic microsomal mixed-function oxygenase activity to less than 20% of control activity, but the same tumor cells growing as free ascites cells in the peritoneal cavity did not. Necrosis of the core area of solid tumors was observed. Tumor cells may release a substance that depresses hepatic microsomal mixed-function oxygenase activity only upon their death."}
{"id": "PMID:28922", "title": "The fate of a major biliary metabolite of digitoxin in the rat intestine.", "content": "In the rat, the major water-soluble biliary metabolite of digotoxin is digitoxigenin monodigitoxoside glucuronide (mono-gluc). Despite its preponderance in the bile, only small amounts of mono-gluc are found in the feces. The compound may be absorbed from the intestine as the glucuronide conjugate, or it may be hydrolyzed to the parent compound, digitoxigenin monodigitoxoside (mono); the parent compound might then be absorbed from the intestine. The purposes of this study were to determine the ability of closed duodenal and cecal strips in vivo to absorb the conjugate and the parent compound, to hydrolyze the glucuronide, and to conjugate the parent mono. Absorption of mono was found to be more rapid than mono-gluc in both intestinal locations. Absorption of mono in the cecal strip was slower than in the duodenal strip. Considerable hydrolysis of mono-gluc occurred in the cecal strip; in the duodenal strip, the net process was conjugated of the parent mono. Thus, the disappearance of mono-gluc between its appearance in the bile and excretion in the feces is explained mainly by hydrolysis in the lower intestinal tract. Paradoxically, absorption of the hydrolysis product, mono, proceeds more slowly in the lower intestine, where it is hydrolyzed, than in the duodenum, where hydrolysis does not occur.", "contents": "The fate of a major biliary metabolite of digitoxin in the rat intestine. In the rat, the major water-soluble biliary metabolite of digotoxin is digitoxigenin monodigitoxoside glucuronide (mono-gluc). Despite its preponderance in the bile, only small amounts of mono-gluc are found in the feces. The compound may be absorbed from the intestine as the glucuronide conjugate, or it may be hydrolyzed to the parent compound, digitoxigenin monodigitoxoside (mono); the parent compound might then be absorbed from the intestine. The purposes of this study were to determine the ability of closed duodenal and cecal strips in vivo to absorb the conjugate and the parent compound, to hydrolyze the glucuronide, and to conjugate the parent mono. Absorption of mono was found to be more rapid than mono-gluc in both intestinal locations. Absorption of mono in the cecal strip was slower than in the duodenal strip. Considerable hydrolysis of mono-gluc occurred in the cecal strip; in the duodenal strip, the net process was conjugated of the parent mono. Thus, the disappearance of mono-gluc between its appearance in the bile and excretion in the feces is explained mainly by hydrolysis in the lower intestinal tract. Paradoxically, absorption of the hydrolysis product, mono, proceeds more slowly in the lower intestine, where it is hydrolyzed, than in the duodenum, where hydrolysis does not occur."}
{"id": "PMID:28923", "title": "Metabolism of benzo[a]pyrene by the isolated perfused rabbit lung.", "content": "The metabolism of benzo[a]pyrene (BP) was studied in the isolated perfused rabbit lung and in rabbit pulmonary microsomes. Pretreatment of rabbits with 3-methylcholanthrene did not increase the metabolism of BP by microsomal preparations, and the pretreatment did not induce cytochrome P-448 in pulmonary microsomes. In the isolated perfused lung, BP was metabolized at a rate of about 6 nmol/min/g of lung. The intermediate arene oxides formed from BP in the isolated perfused lung were metabolized nonoxidatively by epoxide hydrase and glutathione S-transferases. The rates of the latter reactions were at least an order of magnitude less than the overall rate of metabolism. Pretreatment of the animals with 3-methylcholanthrene increased only the apparent rate of the epoxide hydrase reaction. In the isolated perfused lung, BP and some of its less polar metabolites (i.e., quinones and phenolic derivatives) were preferentially partitioned into lung tissue, precluding accurate measurement of metabolic rates by analysis of the perfusion medium alone. Covalent binding of BP-derived radioactivity to lung tissue occurred, but relatively high variability in this parameter in lungs from 3-methylcholanthrene-pretreated animals did not allow measurement of a significant difference from control lungs.", "contents": "Metabolism of benzo[a]pyrene by the isolated perfused rabbit lung. The metabolism of benzo[a]pyrene (BP) was studied in the isolated perfused rabbit lung and in rabbit pulmonary microsomes. Pretreatment of rabbits with 3-methylcholanthrene did not increase the metabolism of BP by microsomal preparations, and the pretreatment did not induce cytochrome P-448 in pulmonary microsomes. In the isolated perfused lung, BP was metabolized at a rate of about 6 nmol/min/g of lung. The intermediate arene oxides formed from BP in the isolated perfused lung were metabolized nonoxidatively by epoxide hydrase and glutathione S-transferases. The rates of the latter reactions were at least an order of magnitude less than the overall rate of metabolism. Pretreatment of the animals with 3-methylcholanthrene increased only the apparent rate of the epoxide hydrase reaction. In the isolated perfused lung, BP and some of its less polar metabolites (i.e., quinones and phenolic derivatives) were preferentially partitioned into lung tissue, precluding accurate measurement of metabolic rates by analysis of the perfusion medium alone. Covalent binding of BP-derived radioactivity to lung tissue occurred, but relatively high variability in this parameter in lungs from 3-methylcholanthrene-pretreated animals did not allow measurement of a significant difference from control lungs."}
{"id": "PMID:28924", "title": "Binding of iophenoxate and iopanoate to human serum albumin.", "content": "Determination of the binding affinities of 125I-labeled cholecystographic agents to human serum albumin by ultrafiltration techniques is complicated by the appearance of radiochemical impurities resulting from radiolysis of the parent compound. With labeled compounds purified daily by two extractions through chloroform, iophenoxic acid has an extremely high binding affinity. The dissociation constant (K) is 0.013 micronM for iophenoxate, compared to 0.15 micronM for iopanoate, its close analogue. However, at the weaker sites, iophenoxic acid is less strongly bound than iopanoate. The exceptionally high affinity of iophenoxate for a single site of serum albumin appears to underlie its unusual persistence in plasma. Binding in vivo is reversible and not covalent in nature. The choleretic compounds cinchophen and taurocholate have differential effects on the biliary excretion of iophenoxate and iopanoate. This cannot be attributed to selective inhibition of binding to plasma protein.", "contents": "Binding of iophenoxate and iopanoate to human serum albumin. Determination of the binding affinities of 125I-labeled cholecystographic agents to human serum albumin by ultrafiltration techniques is complicated by the appearance of radiochemical impurities resulting from radiolysis of the parent compound. With labeled compounds purified daily by two extractions through chloroform, iophenoxic acid has an extremely high binding affinity. The dissociation constant (K) is 0.013 micronM for iophenoxate, compared to 0.15 micronM for iopanoate, its close analogue. However, at the weaker sites, iophenoxic acid is less strongly bound than iopanoate. The exceptionally high affinity of iophenoxate for a single site of serum albumin appears to underlie its unusual persistence in plasma. Binding in vivo is reversible and not covalent in nature. The choleretic compounds cinchophen and taurocholate have differential effects on the biliary excretion of iophenoxate and iopanoate. This cannot be attributed to selective inhibition of binding to plasma protein."}
{"id": "PMID:28925", "title": "Competition for binding to multiple sites of human serum albumin for cholecystographic agents and sulfobromophthalein.", "content": "The binding of two cholecystographic agents, iophenoxate and iopanoate, to human serum albumin was studied with 11 putative competitors; the results were qualitatively consistent with competitive binding to common sites. A more precise analysis of competition was achieved with four pairs of compounds for which the free and bound concentration of each was determined. The results were analyzed by a computer program and the dissociation constants calculated for both binder and competitor at specified sites on albumin. With numbering based on the rank order of dissociation constants for iophenoxate, the highest binding of the four compounds occurs at different sites: iophenoxate at site I; iopanoate at site II, sulfobromophthalein at site III; and bromphenol blue at site II. For a given compound, there is close agreement in the calculated affinities at different sites regardless of the competitor.", "contents": "Competition for binding to multiple sites of human serum albumin for cholecystographic agents and sulfobromophthalein. The binding of two cholecystographic agents, iophenoxate and iopanoate, to human serum albumin was studied with 11 putative competitors; the results were qualitatively consistent with competitive binding to common sites. A more precise analysis of competition was achieved with four pairs of compounds for which the free and bound concentration of each was determined. The results were analyzed by a computer program and the dissociation constants calculated for both binder and competitor at specified sites on albumin. With numbering based on the rank order of dissociation constants for iophenoxate, the highest binding of the four compounds occurs at different sites: iophenoxate at site I; iopanoate at site II, sulfobromophthalein at site III; and bromphenol blue at site II. For a given compound, there is close agreement in the calculated affinities at different sites regardless of the competitor."}
{"id": "PMID:28926", "title": "Prolonged impairment of the plasma-protein binding of phenytoin in the rat after a single dose of sodium oleate.", "content": "The plasma-protein binding of phenytoin in rats was impaired for more than 14 days after a single injection of sodium oleate compared to that observed in saline-treated controls. A maximum free (unbound) phenytoin fraction value of about 0.30 was found between 30 and 120 min after oleate administration. The free fraction decreased to about 0.20 after 14 days. The free fraction of phenytoin in control rats was essentially constant over this period and averaged about 0.17. The impaired plasma-protein binding of phenytoin was unaffected by prolonged dialysis but was effectively reversed by charcoal treatment of the plasma. Comparison of the in vivo and in vitro effects of sodium oleate on phenytoin binding in plasma indicates that the reduction in binding is unrelated to the in vivo oleate concentration in plasma at the time of the binding determination. For example, 5 min after a bolus injection of oleate, the plasma free fraction of phenytoin was about 0.33. A comparable concentration of oleate in control plasma resulted in a free phenytoin fraction of only 0.21.", "contents": "Prolonged impairment of the plasma-protein binding of phenytoin in the rat after a single dose of sodium oleate. The plasma-protein binding of phenytoin in rats was impaired for more than 14 days after a single injection of sodium oleate compared to that observed in saline-treated controls. A maximum free (unbound) phenytoin fraction value of about 0.30 was found between 30 and 120 min after oleate administration. The free fraction decreased to about 0.20 after 14 days. The free fraction of phenytoin in control rats was essentially constant over this period and averaged about 0.17. The impaired plasma-protein binding of phenytoin was unaffected by prolonged dialysis but was effectively reversed by charcoal treatment of the plasma. Comparison of the in vivo and in vitro effects of sodium oleate on phenytoin binding in plasma indicates that the reduction in binding is unrelated to the in vivo oleate concentration in plasma at the time of the binding determination. For example, 5 min after a bolus injection of oleate, the plasma free fraction of phenytoin was about 0.33. A comparable concentration of oleate in control plasma resulted in a free phenytoin fraction of only 0.21."}
{"id": "PMID:28928", "title": "Disposition of 4,5-diphenyl-2-oxazolepropionic acid (oxaprozin) in beagle dogs and rhesus monkeys.", "content": "Following intragastric doses of 14C-oxaprozin to beagle dogs and rhesus monkeys, oxaprozin was rapidly absorbed and was essentially the only drug-related substance in the plasma for at least 24 hr. Recovery of radioactivity in the excreta was 87% in both species, with the fecal route accounting for almost all of the excretion by the dog, and the urinary route predominating in the monkey. The drug was slowly eliminated by both species. The concentrations in tissues of monkeys were generally less than those in plasma, and their decline with time paralleled that in plasma. High concentrations of 14C were found in the bile and urine. Qualitative and quantitative metabolite patterns of both fluids were similar. About 90% of the 14C in both bile and urine was recovered as identified compounds in the free, ester conjugate, and ether conjugate fractions. The ester conjugate fraction, mainly consisting of oxaprozin glucuronide, was quantitatively the most important in both fluids. Two phenolic metabolites were characterized by mass spectrometry and co-chromatography. They were present in free form and as ester and ether glucuronides.", "contents": "Disposition of 4,5-diphenyl-2-oxazolepropionic acid (oxaprozin) in beagle dogs and rhesus monkeys. Following intragastric doses of 14C-oxaprozin to beagle dogs and rhesus monkeys, oxaprozin was rapidly absorbed and was essentially the only drug-related substance in the plasma for at least 24 hr. Recovery of radioactivity in the excreta was 87% in both species, with the fecal route accounting for almost all of the excretion by the dog, and the urinary route predominating in the monkey. The drug was slowly eliminated by both species. The concentrations in tissues of monkeys were generally less than those in plasma, and their decline with time paralleled that in plasma. High concentrations of 14C were found in the bile and urine. Qualitative and quantitative metabolite patterns of both fluids were similar. About 90% of the 14C in both bile and urine was recovered as identified compounds in the free, ester conjugate, and ether conjugate fractions. The ester conjugate fraction, mainly consisting of oxaprozin glucuronide, was quantitatively the most important in both fluids. Two phenolic metabolites were characterized by mass spectrometry and co-chromatography. They were present in free form and as ester and ether glucuronides."}
{"id": "PMID:28929", "title": "The fate of [7-3H]isoproterenol in cats after intravenous administration.", "content": "The fate of intravenously administered [7-3H]isoproterenol was investigated in cats. Ten minutes after injection the concentration of 3H was highest in the heart, lungs, adrenals, and kidneys, but after 5 hr most of the radioactivity was found in the liver. The concentration of the unchanged drug in the serum declined in a biphasic manner with half-lives of 2.1--2.5 min for the first phase, and 58--77 min for the second phase. The drug was rapidly metabolized to 3-O-methylisoproterenol (MISP) and then conjugated. In 5 hr 44--55% of the administered 3H was excreted in the urine, 2--2.5% as unchanged drug, 21--41% as MISP, and 12--22% as conjugated MISP. Conjugated MISP was also found in the bile. The results indicate that the rate of formation of MISP in cats is much faster than its rate of conjugation and excretion.", "contents": "The fate of [7-3H]isoproterenol in cats after intravenous administration. The fate of intravenously administered [7-3H]isoproterenol was investigated in cats. Ten minutes after injection the concentration of 3H was highest in the heart, lungs, adrenals, and kidneys, but after 5 hr most of the radioactivity was found in the liver. The concentration of the unchanged drug in the serum declined in a biphasic manner with half-lives of 2.1--2.5 min for the first phase, and 58--77 min for the second phase. The drug was rapidly metabolized to 3-O-methylisoproterenol (MISP) and then conjugated. In 5 hr 44--55% of the administered 3H was excreted in the urine, 2--2.5% as unchanged drug, 21--41% as MISP, and 12--22% as conjugated MISP. Conjugated MISP was also found in the bile. The results indicate that the rate of formation of MISP in cats is much faster than its rate of conjugation and excretion."}
{"id": "PMID:28930", "title": "O-methylated catechol-like metabolites of propranolol in man.", "content": "Two isomeric methoxyhydroxy metabolites of propranolol have been identified in man during chronic antihypertensive propranolol therapy. The identification was based on the mass-spectral fragmentation pattern of their trifluoroacetylated derivatives. Both isomers were detected in urine as well as in plasma, mainly as glucuronic acid and/or sulfate conjugates. The amounts of these metabolites excreted in urine were linearly related (r = 0.84) to the oral propranolol dose, 10--320 mg per day. Plasma concentrations at the 320-mg daily dose ranged from 20 to 112 ng/ml. Similar isomeric methoxyhydroxy metabolites of propranolol containing a glycol or a lactic acid side-chain were also identified.", "contents": "O-methylated catechol-like metabolites of propranolol in man. Two isomeric methoxyhydroxy metabolites of propranolol have been identified in man during chronic antihypertensive propranolol therapy. The identification was based on the mass-spectral fragmentation pattern of their trifluoroacetylated derivatives. Both isomers were detected in urine as well as in plasma, mainly as glucuronic acid and/or sulfate conjugates. The amounts of these metabolites excreted in urine were linearly related (r = 0.84) to the oral propranolol dose, 10--320 mg per day. Plasma concentrations at the 320-mg daily dose ranged from 20 to 112 ng/ml. Similar isomeric methoxyhydroxy metabolites of propranolol containing a glycol or a lactic acid side-chain were also identified."}
{"id": "PMID:28931", "title": "Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog.", "content": "The metabolism of hydrocodone was studied in man, rat, guinea pig, rabbit, and dog. Routes of metabolism included O-demethylation, N-dealkylation, and 6-keto-reduction to the corresponding 6-alpha- and 6-beta-hydroxy metabolites, where each metabolic pathway produces an active metabolite. Mean total recovery of drug and metabolites as percentage of administered dose ranged from a low of 10.6% for the rabbit to a high of 46.8% for the guinea pig; man was intermediate at 25.7%. For man, approximately 70% of the total drug recovered was excreted in the first 24 hr, and the remainder by 72 hr. Considerable species differences were observed in the patterns of metabolism of hydrocodone. Also, stereoselectivity of 6-keto reduction to the beta-form was observed for all species in the reduction of hydrocodone and hydromorphone with the exception of the reduction of hydrocodone by man.", "contents": "Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog. The metabolism of hydrocodone was studied in man, rat, guinea pig, rabbit, and dog. Routes of metabolism included O-demethylation, N-dealkylation, and 6-keto-reduction to the corresponding 6-alpha- and 6-beta-hydroxy metabolites, where each metabolic pathway produces an active metabolite. Mean total recovery of drug and metabolites as percentage of administered dose ranged from a low of 10.6% for the rabbit to a high of 46.8% for the guinea pig; man was intermediate at 25.7%. For man, approximately 70% of the total drug recovered was excreted in the first 24 hr, and the remainder by 72 hr. Considerable species differences were observed in the patterns of metabolism of hydrocodone. Also, stereoselectivity of 6-keto reduction to the beta-form was observed for all species in the reduction of hydrocodone and hydromorphone with the exception of the reduction of hydrocodone by man."}
{"id": "PMID:28936", "title": "[The effect of etilefrine and dihydroergotamine on sympathetic nervous system activity when standing up (author's transl)].", "content": "Systolic blood pressure, heart rate and concentrations of adrenaline, noradrenaline and dopamine as well as plasma dopamine-beta-hydroxylase (DBH) were measured in 22 subjects in recumbency and on standing up. Six subjects each had previously been given intravenously dihydroergotamine (0.5 mg) or etilefrine (0.25 mg/min) or a placebo. It was demonstrated that orthostasis leads to an increased activity of the sympathetic nervous system and the adrenal system. After administration of dihydroergotamine there was a diminished reaction of the sympathetic nervous system with an increase of venous tone which counteracted the decrease in cardiac output. Etilefrine, on the other hand, inhibited the sympatho-adrenal reaction on orthostasis and decreased the liberation of adrenaline. It acts directly via stimulation of alpha-and beta-receptors and is thus predominantly indicated if there is insufficient response of the baroreceptor reflex at its efferent limb.", "contents": "[The effect of etilefrine and dihydroergotamine on sympathetic nervous system activity when standing up (author's transl)]. Systolic blood pressure, heart rate and concentrations of adrenaline, noradrenaline and dopamine as well as plasma dopamine-beta-hydroxylase (DBH) were measured in 22 subjects in recumbency and on standing up. Six subjects each had previously been given intravenously dihydroergotamine (0.5 mg) or etilefrine (0.25 mg/min) or a placebo. It was demonstrated that orthostasis leads to an increased activity of the sympathetic nervous system and the adrenal system. After administration of dihydroergotamine there was a diminished reaction of the sympathetic nervous system with an increase of venous tone which counteracted the decrease in cardiac output. Etilefrine, on the other hand, inhibited the sympatho-adrenal reaction on orthostasis and decreased the liberation of adrenaline. It acts directly via stimulation of alpha-and beta-receptors and is thus predominantly indicated if there is insufficient response of the baroreceptor reflex at its efferent limb."}
{"id": "PMID:28932", "title": "Characterization of glucuronide metabolites of carbamazepine in human urine by gas chromatography and mass spectrometry.", "content": "Glucuronide metabolites of carbamazepine (5 H-dibenz[b,f]azepine-5-carboxamide) were identified in human urine following chromatography on XAD-2 resin, permethylation, and combined gas chromatography and mass spectrometry with an SE-30 capillary column. Eight glucuronide metabolites, previously unidentified in man, were characterized as their permethylated derivatives. These included carbamazepine N-glucuronide (M+. 482), three isomers of dihydroxycarbamazepine O-glucuronide (M+. 542), three isomers of hydroxymethoxycarbamazepine O-glucuronide (M+. 542), and one isomer of hydroxycarbamazepine O-glucuronide (M+. 512). Other glucuronide metabolites, previously identified following enzymatic hydrolysis, were characterized as the unhydrolyzed, permethylated glucuronides, 10,11-dihydro-10,11-di--hydroxy carbamazepine O-glucuronide (M+. 544), and three isomers of monohydroxycarbamazepine O-glucuronide (M+. 512).", "contents": "Characterization of glucuronide metabolites of carbamazepine in human urine by gas chromatography and mass spectrometry. Glucuronide metabolites of carbamazepine (5 H-dibenz[b,f]azepine-5-carboxamide) were identified in human urine following chromatography on XAD-2 resin, permethylation, and combined gas chromatography and mass spectrometry with an SE-30 capillary column. Eight glucuronide metabolites, previously unidentified in man, were characterized as their permethylated derivatives. These included carbamazepine N-glucuronide (M+. 482), three isomers of dihydroxycarbamazepine O-glucuronide (M+. 542), three isomers of hydroxymethoxycarbamazepine O-glucuronide (M+. 542), and one isomer of hydroxycarbamazepine O-glucuronide (M+. 512). Other glucuronide metabolites, previously identified following enzymatic hydrolysis, were characterized as the unhydrolyzed, permethylated glucuronides, 10,11-dihydro-10,11-di--hydroxy carbamazepine O-glucuronide (M+. 544), and three isomers of monohydroxycarbamazepine O-glucuronide (M+. 512)."}
{"id": "PMID:28939", "title": "[Comparative trials on sultopride and fluanisone].", "content": "A therapeutic trial has been carried out on 50 patients, most of them being hospitalized, in order to compare the characteristics of a new benzamide, Sultopride, to those of a butyrophenone, Fluanisone, for the treatment of important and chronic agitation states. Clinically, they were essentially psychotic states, with dissociation. From this trial it appeared that sultopride is superior to fluanizone with regard to their sedative effects and that it has specific characteristics: a very powerful antipsychotic action, an increasing efficiency over time, as well as an improvement of incoercible agitation in children. Thus, the present trial has checked out the well-known sedative action of Fluanisone, and has revealed a new major antipsychotic drug, Sultopride, the superiority of which lies on a much wider therapeutic field.", "contents": "[Comparative trials on sultopride and fluanisone]. A therapeutic trial has been carried out on 50 patients, most of them being hospitalized, in order to compare the characteristics of a new benzamide, Sultopride, to those of a butyrophenone, Fluanisone, for the treatment of important and chronic agitation states. Clinically, they were essentially psychotic states, with dissociation. From this trial it appeared that sultopride is superior to fluanizone with regard to their sedative effects and that it has specific characteristics: a very powerful antipsychotic action, an increasing efficiency over time, as well as an improvement of incoercible agitation in children. Thus, the present trial has checked out the well-known sedative action of Fluanisone, and has revealed a new major antipsychotic drug, Sultopride, the superiority of which lies on a much wider therapeutic field."}
{"id": "PMID:28940", "title": "[Mental complications of neuroleptic drugs. Confusional oneiric states].", "content": "The author reports five cases of relatively young women, in good general health, except that one of them had alcoholic liver disease, who presented a confusional state on taking neuroleptics: a widely used butyrophenone, prescribed for a psychotic condition. Owing to the low incidence of this side effect, these clinical cases were worth reporting. Furthermore, a trial of interpretation led us to believe that these reductions in consciousness were due to resistance to treatment.", "contents": "[Mental complications of neuroleptic drugs. Confusional oneiric states]. The author reports five cases of relatively young women, in good general health, except that one of them had alcoholic liver disease, who presented a confusional state on taking neuroleptics: a widely used butyrophenone, prescribed for a psychotic condition. Owing to the low incidence of this side effect, these clinical cases were worth reporting. Furthermore, a trial of interpretation led us to believe that these reductions in consciousness were due to resistance to treatment."}
{"id": "PMID:28941", "title": "beta-adrenergic blocking drugs in psychiatry: present status, future approaches and research.", "content": "Clinical trials with propranolol were performed in 44 carefully selected psychiatric patients. Propranolol was administered in 8 equal doses over 24 hours and increased at a daily rate of 400 mg. Treatment was monitored by patient's reactions and by periodic examination of pulse rate and blood pressure. Results showed marked to moderate improvement, often within 24 to 48 hours, in two-thirds of the patients treated. Concurrent with stabilization of heart rate and blood pressure at about 60/min and 90/60 mm Hg respectively, improvement was noted in anxiety, psychomotor hyperactivity, thought process disturbance, hallucinations, and disturbances in affect. Our studies and those of other investigators indicate that propranolol and oxprenolol, and possibly other beta-adrenoceptor blocking drugs, may have a beneficial influence on psychotic syndromes. Further well-controlled clinical trials seem warranted. Indications for use, dosages, and combinations with other drugs, mainly phenothiazines, must be delineated. Laboratory investigations may add considerably in these respects ans may lead to safe treatment regimes with minimal side effects.", "contents": "beta-adrenergic blocking drugs in psychiatry: present status, future approaches and research. Clinical trials with propranolol were performed in 44 carefully selected psychiatric patients. Propranolol was administered in 8 equal doses over 24 hours and increased at a daily rate of 400 mg. Treatment was monitored by patient's reactions and by periodic examination of pulse rate and blood pressure. Results showed marked to moderate improvement, often within 24 to 48 hours, in two-thirds of the patients treated. Concurrent with stabilization of heart rate and blood pressure at about 60/min and 90/60 mm Hg respectively, improvement was noted in anxiety, psychomotor hyperactivity, thought process disturbance, hallucinations, and disturbances in affect. Our studies and those of other investigators indicate that propranolol and oxprenolol, and possibly other beta-adrenoceptor blocking drugs, may have a beneficial influence on psychotic syndromes. Further well-controlled clinical trials seem warranted. Indications for use, dosages, and combinations with other drugs, mainly phenothiazines, must be delineated. Laboratory investigations may add considerably in these respects ans may lead to safe treatment regimes with minimal side effects."}
{"id": "PMID:28945", "title": "Alkylation of 6-phosphogluconate dehydrogenase from Candida utilis with coenzyme analogues.", "content": "The mechanism of the inactivation of 6-phosphogluconate dehydrogenase from Candida utilis with two coenzyme analogues can be differentiated on the basis of kinetic studies and of the properties of the inactivated enzyme. 3-Chloroacetylpyridine--adenine dinucleotide phosphate is clearly an affinity label and 3-choloroacetylpyridine--adenine dinucleotide a second-order reagent. For 3-chloroacetylpyridine--adenine dinucleotide phosphate, there is a loss of one thiol per subunit at complete inactivation whereas for 3-chloroacetylpyridine--adenine dinucleotide 2.7 thiol groups are lost. The fluorescence of the protein is quenched after alkylation by 3-chloroacetylpyridine--adenine dinucleotide phosphate and there is no quenching after the inactivation with 3-chloroacetylpyridine--adenine dinucleotide.", "contents": "Alkylation of 6-phosphogluconate dehydrogenase from Candida utilis with coenzyme analogues. The mechanism of the inactivation of 6-phosphogluconate dehydrogenase from Candida utilis with two coenzyme analogues can be differentiated on the basis of kinetic studies and of the properties of the inactivated enzyme. 3-Chloroacetylpyridine--adenine dinucleotide phosphate is clearly an affinity label and 3-choloroacetylpyridine--adenine dinucleotide a second-order reagent. For 3-chloroacetylpyridine--adenine dinucleotide phosphate, there is a loss of one thiol per subunit at complete inactivation whereas for 3-chloroacetylpyridine--adenine dinucleotide 2.7 thiol groups are lost. The fluorescence of the protein is quenched after alkylation by 3-chloroacetylpyridine--adenine dinucleotide phosphate and there is no quenching after the inactivation with 3-chloroacetylpyridine--adenine dinucleotide."}
{"id": "PMID:28946", "title": "Cryoenzymologic studies on arginine kinase: solvent, temperature and pH effects on the overall reaction.", "content": "The overall reaction catalyzed by the phosphotransferase arginine kinase was studied at normal and subzero temperatures. Ethylene glycol was used as the antifreeze and its effects on the Km values of substances, kcat and pH profiles were investigated in detail. a) The Km values for the substrate (2 mM for ATP and 0.6 mM for arginine) were little affected by the solvent composition or temperature of the reaction mixture. b) At concentration of ethylene glycol higher than 40% there was a sharp drop of enzyme activity. c) Ethylene glycol induces a large shift in the enzymic pK D) At -5 degrees C in 40% of solvent there was a break in the Arrhenius plot suggesting a change of the rate-limiting step. The relevance of these results to the reaction pathway of arginine kinase is discussed. In addition, controlled perturbations induced by cosolvent and temperature appear as useful tools for further kinetic investigations.", "contents": "Cryoenzymologic studies on arginine kinase: solvent, temperature and pH effects on the overall reaction. The overall reaction catalyzed by the phosphotransferase arginine kinase was studied at normal and subzero temperatures. Ethylene glycol was used as the antifreeze and its effects on the Km values of substances, kcat and pH profiles were investigated in detail. a) The Km values for the substrate (2 mM for ATP and 0.6 mM for arginine) were little affected by the solvent composition or temperature of the reaction mixture. b) At concentration of ethylene glycol higher than 40% there was a sharp drop of enzyme activity. c) Ethylene glycol induces a large shift in the enzymic pK D) At -5 degrees C in 40% of solvent there was a break in the Arrhenius plot suggesting a change of the rate-limiting step. The relevance of these results to the reaction pathway of arginine kinase is discussed. In addition, controlled perturbations induced by cosolvent and temperature appear as useful tools for further kinetic investigations."}
{"id": "PMID:28947", "title": "Production of NADPH in the mannitol cycle and its relation to polyketide formation in Alternaria alternata.", "content": "The enzymes mannitol-1-phosphate dehydrogenase, mannitol-1-phosphatase, mannitol dehydrogenase and hexokinase participate in an enzymatic cycle in the fungus Alternaria alternata. One turn of the cycle gives the net result: NADH + NADP+ + ATP leads to NAD+ + NADPH + ADP + Pi. The cycle alone can meet the total need of NADPH formation for fat synthesis in the organism. A polyketide producing strain of A. alternata shows a lower mannitol oxidation as well as a lower fat synthesis than a nonproducing mutant, supporting the hypothesis that polyketide formation is favoured at limiting NADPH production. It is further suggested that the mannitol cycle is regulating the glycolytic flux by substrate withdrawal from phosphofructokinase.", "contents": "Production of NADPH in the mannitol cycle and its relation to polyketide formation in Alternaria alternata. The enzymes mannitol-1-phosphate dehydrogenase, mannitol-1-phosphatase, mannitol dehydrogenase and hexokinase participate in an enzymatic cycle in the fungus Alternaria alternata. One turn of the cycle gives the net result: NADH + NADP+ + ATP leads to NAD+ + NADPH + ADP + Pi. The cycle alone can meet the total need of NADPH formation for fat synthesis in the organism. A polyketide producing strain of A. alternata shows a lower mannitol oxidation as well as a lower fat synthesis than a nonproducing mutant, supporting the hypothesis that polyketide formation is favoured at limiting NADPH production. It is further suggested that the mannitol cycle is regulating the glycolytic flux by substrate withdrawal from phosphofructokinase."}
{"id": "PMID:28948", "title": "Factors modifying equilibrium between activated and non-activated forms of steroid-receptor complexes.", "content": "Steroid-receptor complexes formed in concentrated cytosol at low temperature, low ionic strength and neutral pH are unable to bind to nuclei. Various procedures are known to promote their 'activation'. In the present work it is shown that an increase in temperature only enhances the rate of the reaction whereas no change in the equilibrium between activated and non-activated complexes is observed. On the contrary an increase in ionic strength or pH, as well as a removal of a low-molecular-weight inhibitor, not only accelerate the reaction but also increase the concentration of activated complexes at equilibrium. Using two steroids differing 3-fold in their affinity for the receptor, no difference was seen in the effect of the bound steroid on receptor activation. When combining various activation procedures it was observed that they acted independently of each other and additively. In all cases they retained their property of either modifying only the rate of the reaction or both its rate and equilibrium. Using changes in pH, it was also possible to induce shifts in the equilibrium between activated and non-activated complexes. After activation at pH 6.5, a first equilibrium was attained. When the pH was increased to 8 the equilibrium was displaced towards higher concentrations of activated complexes. A lowering of the pH resulted in a reversal of steroid-receptor complexes from the activated to the non-activated state. To clearly establish that this was not due to irreversible damage of the receptor, which would render it unable to bind to nuclei, it was shown that the complexes which had reverted to the non-activated state were still susceptible to activation. Regulatory events may thus exist which, for a given level of hormone and receptor, modulate the concentration of activated steroid-receptor complexes.", "contents": "Factors modifying equilibrium between activated and non-activated forms of steroid-receptor complexes. Steroid-receptor complexes formed in concentrated cytosol at low temperature, low ionic strength and neutral pH are unable to bind to nuclei. Various procedures are known to promote their 'activation'. In the present work it is shown that an increase in temperature only enhances the rate of the reaction whereas no change in the equilibrium between activated and non-activated complexes is observed. On the contrary an increase in ionic strength or pH, as well as a removal of a low-molecular-weight inhibitor, not only accelerate the reaction but also increase the concentration of activated complexes at equilibrium. Using two steroids differing 3-fold in their affinity for the receptor, no difference was seen in the effect of the bound steroid on receptor activation. When combining various activation procedures it was observed that they acted independently of each other and additively. In all cases they retained their property of either modifying only the rate of the reaction or both its rate and equilibrium. Using changes in pH, it was also possible to induce shifts in the equilibrium between activated and non-activated complexes. After activation at pH 6.5, a first equilibrium was attained. When the pH was increased to 8 the equilibrium was displaced towards higher concentrations of activated complexes. A lowering of the pH resulted in a reversal of steroid-receptor complexes from the activated to the non-activated state. To clearly establish that this was not due to irreversible damage of the receptor, which would render it unable to bind to nuclei, it was shown that the complexes which had reverted to the non-activated state were still susceptible to activation. Regulatory events may thus exist which, for a given level of hormone and receptor, modulate the concentration of activated steroid-receptor complexes."}
{"id": "PMID:28952", "title": "Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction.", "content": "To investigate the initial potassium loss and development of hypokalaemia during the administration of an oral diuretic, metabolic balance studies were performed in ten patients with essential hypertension who had shown hypokalaemia under prior oral diuretic treatment. Chlorthalidone (50 mg daily) was given for 14 days. Six patients received a normal-sodium diet and four a low-sodium (17 mmol/day) diet. All patients had a normal initial total body potassium (40K). The electrolyte balances, weight, bromide space, plasma renin activity, and aldosterone secretion rate were measured. In both groups a potassium deficit developed, with proportionally larger losses from the extracellular than from the intracellular compartment. In the normal-sodium group the highest mean potassium deficit was 176 mmol on day 9, after which some potassium was regained; in the low-sodium group the highest deficit was 276 mmol on day 13. The normal-sodium group showed an immediate but temporary rise of the renin and aldosterone levels; in the low-sodium group renin and aldosterone increased more slowly but remained elevated. It is concluded that dietary sodium restriction increases diuretic-induced potassium loss, presumably by an increased activity of the renin-angiotensin-aldosterone system, while sodium delivery to the distal renal tubules remains sufficiently high to allow increased potassium secretion.", "contents": "Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction. To investigate the initial potassium loss and development of hypokalaemia during the administration of an oral diuretic, metabolic balance studies were performed in ten patients with essential hypertension who had shown hypokalaemia under prior oral diuretic treatment. Chlorthalidone (50 mg daily) was given for 14 days. Six patients received a normal-sodium diet and four a low-sodium (17 mmol/day) diet. All patients had a normal initial total body potassium (40K). The electrolyte balances, weight, bromide space, plasma renin activity, and aldosterone secretion rate were measured. In both groups a potassium deficit developed, with proportionally larger losses from the extracellular than from the intracellular compartment. In the normal-sodium group the highest mean potassium deficit was 176 mmol on day 9, after which some potassium was regained; in the low-sodium group the highest deficit was 276 mmol on day 13. The normal-sodium group showed an immediate but temporary rise of the renin and aldosterone levels; in the low-sodium group renin and aldosterone increased more slowly but remained elevated. It is concluded that dietary sodium restriction increases diuretic-induced potassium loss, presumably by an increased activity of the renin-angiotensin-aldosterone system, while sodium delivery to the distal renal tubules remains sufficiently high to allow increased potassium secretion."}
{"id": "PMID:28954", "title": "alpha- and beta-receptor blockade of isoproterenol- and norepinephrine-induced effects on regional blood flow and blood flow acceleration.", "content": "The effects of the beta-receptor blocking agent propranolol (100 microgram/kg i.v.) and of the alpha-receptor blocking agent dihydroergotamine (50 microgram/kg i.v.) on hemodynamic responses to isoproterenol and norepinephrine (both 1--1024 ng/kg) were investigated in anesthetized dogs. The effects studied were: (1) flow in the ascending aorta and the coronary, common hepatic, gastroduodenal, splenic, cranial mesenteric, renal and femoral arteries: (2) maximal flow acceleration in the splenic, cranial mesenteric and femoral arteries; (3) maximal rate of change of left ventricular pressure (LV dP/dt max). Propranolol shifted the dose-response curves for the isoproterenol-induced flow increases in the common hepatic, gastro-duodenal, and cranial mesenteric arteries to the right. It did not influence the flow responses to isoproterenol in the ascending aorta or the coronary, splenic, renal and femoral arteries. Propranolol prevented the decrease of arterial pressure evoked by isoproterenol. Propranolol shifted the isoproterenol-induced increase of LV dP/dt max and maximal blood flow to the same extent. Propranolol blocked the flow to the liver and gastrointestinal tract to a greater extent than the LV dP/dt max and maximal flow acceleration. Propranolol had no effect on the norepinephrine-induced increases in flow in the splenic, femoral and coronary arteries, but blocked the norepinephrine-evoked increases of flow accelerations and LV dP/dt max to the same extent. Dihydroergotamine inhibited the norepinephrine-induced increase in flow in the femoral artery and the decreases in flow in the hepatic, splenic, cranial mesenteric and renal arteries, and reversed the reduction of flow in the gastroduodenal artery. It is argued that dihydroergotamine may inhibit the increase in femoral flow through two mechanisms: (1) blocking the flow reduction to norepinephrine in the abdomen, and thereby passively shunting blood from the abdomen in preference to the femoral bed; (2) attenuating the norepinephrine-evoked reflexogenic femoral vasodilatation. It is concluded that: (1) propranolol is a beta-receptor blocking agent with a preference for blockade of isoproterenol-induced vascular effects; (2) norepinephrine-induced flow increases are not direct actions on vascular beta-receptors; (3) the increase of maximal blood flow accelerations after isoproterenol and norepinephrine is mediated by stimulation of cardiac beta-receptors; (4) dihydroergotamine is an alpha-receptor blocking agent particularly in the splanchnic vascular region.", "contents": "alpha- and beta-receptor blockade of isoproterenol- and norepinephrine-induced effects on regional blood flow and blood flow acceleration. The effects of the beta-receptor blocking agent propranolol (100 microgram/kg i.v.) and of the alpha-receptor blocking agent dihydroergotamine (50 microgram/kg i.v.) on hemodynamic responses to isoproterenol and norepinephrine (both 1--1024 ng/kg) were investigated in anesthetized dogs. The effects studied were: (1) flow in the ascending aorta and the coronary, common hepatic, gastroduodenal, splenic, cranial mesenteric, renal and femoral arteries: (2) maximal flow acceleration in the splenic, cranial mesenteric and femoral arteries; (3) maximal rate of change of left ventricular pressure (LV dP/dt max). Propranolol shifted the dose-response curves for the isoproterenol-induced flow increases in the common hepatic, gastro-duodenal, and cranial mesenteric arteries to the right. It did not influence the flow responses to isoproterenol in the ascending aorta or the coronary, splenic, renal and femoral arteries. Propranolol prevented the decrease of arterial pressure evoked by isoproterenol. Propranolol shifted the isoproterenol-induced increase of LV dP/dt max and maximal blood flow to the same extent. Propranolol blocked the flow to the liver and gastrointestinal tract to a greater extent than the LV dP/dt max and maximal flow acceleration. Propranolol had no effect on the norepinephrine-induced increases in flow in the splenic, femoral and coronary arteries, but blocked the norepinephrine-evoked increases of flow accelerations and LV dP/dt max to the same extent. Dihydroergotamine inhibited the norepinephrine-induced increase in flow in the femoral artery and the decreases in flow in the hepatic, splenic, cranial mesenteric and renal arteries, and reversed the reduction of flow in the gastroduodenal artery. It is argued that dihydroergotamine may inhibit the increase in femoral flow through two mechanisms: (1) blocking the flow reduction to norepinephrine in the abdomen, and thereby passively shunting blood from the abdomen in preference to the femoral bed; (2) attenuating the norepinephrine-evoked reflexogenic femoral vasodilatation. It is concluded that: (1) propranolol is a beta-receptor blocking agent with a preference for blockade of isoproterenol-induced vascular effects; (2) norepinephrine-induced flow increases are not direct actions on vascular beta-receptors; (3) the increase of maximal blood flow accelerations after isoproterenol and norepinephrine is mediated by stimulation of cardiac beta-receptors; (4) dihydroergotamine is an alpha-receptor blocking agent particularly in the splanchnic vascular region."}
{"id": "PMID:28955", "title": "The action of CNS drugs on an isolated sympathetic nerve preparation of rabbit.", "content": "The effect of some centrally active drugs on the transmission of nerve impulses through the isolated cervical sympathetic nerve and superior cervical ganglion of the rabbit has been studied by recording both preganglionic and ganglionic responses to single square wave stimuli. Chlorpromazine, trifluoperazine and haloperidol have a greater axonal depressant action than the known local anaesthetics procaine and xylocaine. Chlordiazepoxide and diazepam are similar in local anaesthetic potency to procaine while meprobamate and sodium pentobarbitone possess only slight axonal depressant properties. Meprobamate, sodium pentobarbitone and possibly diazepam have ganglion blocking properties while procaine, chlorpromazine, trifluoperazine, haloperidol and chlordiazepoxide reduce the ganglion potential by virtue of their preganglionic action.", "contents": "The action of CNS drugs on an isolated sympathetic nerve preparation of rabbit. The effect of some centrally active drugs on the transmission of nerve impulses through the isolated cervical sympathetic nerve and superior cervical ganglion of the rabbit has been studied by recording both preganglionic and ganglionic responses to single square wave stimuli. Chlorpromazine, trifluoperazine and haloperidol have a greater axonal depressant action than the known local anaesthetics procaine and xylocaine. Chlordiazepoxide and diazepam are similar in local anaesthetic potency to procaine while meprobamate and sodium pentobarbitone possess only slight axonal depressant properties. Meprobamate, sodium pentobarbitone and possibly diazepam have ganglion blocking properties while procaine, chlorpromazine, trifluoperazine, haloperidol and chlordiazepoxide reduce the ganglion potential by virtue of their preganglionic action."}
{"id": "PMID:28959", "title": "Micro-electrophoretic studies in the cat pulvinar region: effect of acetylcholine.", "content": "1. In the posterior half of the pulvinar of cats anaesthetized with halothane and nitrous oxide, the majority of neurons were fired by ACh released with small electrophoretic currents. In the anterior part of that nucleus, ACh had more variable effects: excitation, depression or none. 2. In comparison with L-glutamate, DL-homocysteic acid and DL-aspartic acid, ACh appeared to be the most potent excitant. 3. ACh-induced discharges were easily and reversibly blocked by low doses of atropine. In most cases, ACh effects could not be blocked selectively by mecamylamine or dihydro-beta-erythroidine. 4. Nicotine failed to mimic ACh, whereas carbachol was a potent excitant and was readily blocked by low doses of atropine. 5. The histochemical reaction to acetylcholinesterase was moderate in the pulvinar. 6. These observations support the view that pulvinar cells differ from other thalamic cells.", "contents": "Micro-electrophoretic studies in the cat pulvinar region: effect of acetylcholine. 1. In the posterior half of the pulvinar of cats anaesthetized with halothane and nitrous oxide, the majority of neurons were fired by ACh released with small electrophoretic currents. In the anterior part of that nucleus, ACh had more variable effects: excitation, depression or none. 2. In comparison with L-glutamate, DL-homocysteic acid and DL-aspartic acid, ACh appeared to be the most potent excitant. 3. ACh-induced discharges were easily and reversibly blocked by low doses of atropine. In most cases, ACh effects could not be blocked selectively by mecamylamine or dihydro-beta-erythroidine. 4. Nicotine failed to mimic ACh, whereas carbachol was a potent excitant and was readily blocked by low doses of atropine. 5. The histochemical reaction to acetylcholinesterase was moderate in the pulvinar. 6. These observations support the view that pulvinar cells differ from other thalamic cells."}
{"id": "PMID:28960", "title": "Response characteristics of semicircular canal and otolith systems in cat. I. Dynamic responses of primary vestibular fibers.", "content": "1. The activity of cat semicircular canal and otolith afferents was studied during yaw and roll rotations, respectively, to examine their dynamic behavior. 2. A sinusoidal analysis of the canal afferent activities showed that their dynamic characteristics are similar to those of second order vestibular neurons, except for a two to three-fold lower absolute gain. This agrees with earlier studies using angular acceleration steps. 3. Both divisions of the eighth nerve were sampled so as to examine afferents from both the utriculus and sacculus. Within the range of inputs used (+/- 25 degrees lateral tilt), the presumed sacular afferents (inferior division) showed either a gamma- or beta-response. However, the gain of their response was generally much less than for the afferents of the superior division (mostly utricular). This behavior is to be expected on the basis of receptor orientations and the components of gravity acting upon the macular receptors. 4. In response to ramp changes in angular position, some otolith units showed a phasic-tonic response pattern, i.e., an overshoot followed by an adaptation to a new steady state level of activity. The majority of units showed predominantly tonic responses proportional to displacement. 5. During sinusoidal rotations the predominantly tonic units showed small phase leads of 0 to 15 degrees at 0.025 Hz which remained constant or decreased to 0 to -15 degrees at 1.0 Hz. The gains were flat or increased by up to 2 fold. The phasic-tonic units showed greater phase leads, 10 to 50 degrees, and gains which increased from 2 to 8 fold. 6. This behavior of otolith afferents suggests that they can provide information about both the magnitude and the rate of change of linear acceleration stimuli.", "contents": "Response characteristics of semicircular canal and otolith systems in cat. I. Dynamic responses of primary vestibular fibers. 1. The activity of cat semicircular canal and otolith afferents was studied during yaw and roll rotations, respectively, to examine their dynamic behavior. 2. A sinusoidal analysis of the canal afferent activities showed that their dynamic characteristics are similar to those of second order vestibular neurons, except for a two to three-fold lower absolute gain. This agrees with earlier studies using angular acceleration steps. 3. Both divisions of the eighth nerve were sampled so as to examine afferents from both the utriculus and sacculus. Within the range of inputs used (+/- 25 degrees lateral tilt), the presumed sacular afferents (inferior division) showed either a gamma- or beta-response. However, the gain of their response was generally much less than for the afferents of the superior division (mostly utricular). This behavior is to be expected on the basis of receptor orientations and the components of gravity acting upon the macular receptors. 4. In response to ramp changes in angular position, some otolith units showed a phasic-tonic response pattern, i.e., an overshoot followed by an adaptation to a new steady state level of activity. The majority of units showed predominantly tonic responses proportional to displacement. 5. During sinusoidal rotations the predominantly tonic units showed small phase leads of 0 to 15 degrees at 0.025 Hz which remained constant or decreased to 0 to -15 degrees at 1.0 Hz. The gains were flat or increased by up to 2 fold. The phasic-tonic units showed greater phase leads, 10 to 50 degrees, and gains which increased from 2 to 8 fold. 6. This behavior of otolith afferents suggests that they can provide information about both the magnitude and the rate of change of linear acceleration stimuli."}
{"id": "PMID:28961", "title": "Biochemical and anatomical adaptation of the lung to oxygen-induced injury.", "content": "A review of anatomical and biochemical responses of the lung to high concentrations of oxygen leads us to postulate a biphasic adaptive response. The early phase entails a defense against life-threatening pulmonary edema engendered by destruction of oxygen susceptible cells forming most of the air-blood interface. This defense is brought about by type II alveolar cell replication to reform a continuous epithelial layer in the alveoli; its success would depend upon the rapidly with which this continuity can be reestablished. Factors favoring a successful defense would include an initial large population of type II cells or the ability of type II cells to divide fast enough to reestablish continuity before of oxygen-sensitive cells (type 1 alveolar epithelial and endothelial cells) proceeds to fatal pulmonary edema; both conditions probably exist in young animals, which are known to be more resistant to hyperoxia than old animals. The second phase of adaptation would require the development of increased tolerance of previously susceptible cells to continued exposure to high oxygen concentrations to prevent their total destruction. We postulate that here the development of new biochemical defenses or the augmentation of those previously present would play a major role.", "contents": "Biochemical and anatomical adaptation of the lung to oxygen-induced injury. A review of anatomical and biochemical responses of the lung to high concentrations of oxygen leads us to postulate a biphasic adaptive response. The early phase entails a defense against life-threatening pulmonary edema engendered by destruction of oxygen susceptible cells forming most of the air-blood interface. This defense is brought about by type II alveolar cell replication to reform a continuous epithelial layer in the alveoli; its success would depend upon the rapidly with which this continuity can be reestablished. Factors favoring a successful defense would include an initial large population of type II cells or the ability of type II cells to divide fast enough to reestablish continuity before of oxygen-sensitive cells (type 1 alveolar epithelial and endothelial cells) proceeds to fatal pulmonary edema; both conditions probably exist in young animals, which are known to be more resistant to hyperoxia than old animals. The second phase of adaptation would require the development of increased tolerance of previously susceptible cells to continued exposure to high oxygen concentrations to prevent their total destruction. We postulate that here the development of new biochemical defenses or the augmentation of those previously present would play a major role."}
{"id": "PMID:28965", "title": "Hemolytic assay of complement and its components from Syrian hamster (Mesocricetus auratus) and Mongolian gerbil (Mariones unguiculatus).", "content": "Syrian hamster sera may be assayed for hemolytic complement (C) activity by standard procedures with sensitized sheep erythrocytes as used for human sera, but mongolian gerbil sera had higher complement titers when tested with sensitized guinea pig erythrocytes as target cells. The optimal conditions for in vitro testing of hamster C were pH 7.3, ionic strength 0.15, and presence of 1 micrometer of Mg2+ and 0.3 micrometer Ca2+. For gerbil C the optimum pH was 8, ionic strength 0.074, and the same concentration of Mg2+ and Ca2+ as for hamster. Incubation at 37 degrees C for 60 minutes yielded optimal results. Complement components in the serum of both species could be tested with commercially prepared intermediates of sheep erythrocytes pretreated with guinea pig C1 and human C4 respectively, using purified human C2 through 9 and standard methods applied for testing human C components. Both species have all nine components of the complement system.", "contents": "Hemolytic assay of complement and its components from Syrian hamster (Mesocricetus auratus) and Mongolian gerbil (Mariones unguiculatus). Syrian hamster sera may be assayed for hemolytic complement (C) activity by standard procedures with sensitized sheep erythrocytes as used for human sera, but mongolian gerbil sera had higher complement titers when tested with sensitized guinea pig erythrocytes as target cells. The optimal conditions for in vitro testing of hamster C were pH 7.3, ionic strength 0.15, and presence of 1 micrometer of Mg2+ and 0.3 micrometer Ca2+. For gerbil C the optimum pH was 8, ionic strength 0.074, and the same concentration of Mg2+ and Ca2+ as for hamster. Incubation at 37 degrees C for 60 minutes yielded optimal results. Complement components in the serum of both species could be tested with commercially prepared intermediates of sheep erythrocytes pretreated with guinea pig C1 and human C4 respectively, using purified human C2 through 9 and standard methods applied for testing human C components. Both species have all nine components of the complement system."}
{"id": "PMID:28968", "title": "Benign hydatidiform mole in Ibadan, Nigeria.", "content": "A study was conducted to analyze 61 patients with benign hydatidiform mole (HM) who were admitted to the University College Hospital in Ibadan, Nigeria, during a 5-year period. The hospital incidence of HM was 1:205 pregnancies, and the condition was seen most commonly in young women, probably because early marriage is customary in our culture. Management of the condition generally was conservative because of the patients' youth. There was no correlation between HM and parity. Vaginal secondaries due to an embolic phenomenon were detected in 5% of the patients. Subsequent pregnancies followed within 6 months of treatment because the majority of the patients failed to heed medical advice to delay pregnancy for 2 years. No diagnostic problems were encountered in the patients who became pregnant during the follow-up period.", "contents": "Benign hydatidiform mole in Ibadan, Nigeria. A study was conducted to analyze 61 patients with benign hydatidiform mole (HM) who were admitted to the University College Hospital in Ibadan, Nigeria, during a 5-year period. The hospital incidence of HM was 1:205 pregnancies, and the condition was seen most commonly in young women, probably because early marriage is customary in our culture. Management of the condition generally was conservative because of the patients' youth. There was no correlation between HM and parity. Vaginal secondaries due to an embolic phenomenon were detected in 5% of the patients. Subsequent pregnancies followed within 6 months of treatment because the majority of the patients failed to heed medical advice to delay pregnancy for 2 years. No diagnostic problems were encountered in the patients who became pregnant during the follow-up period."}
{"id": "PMID:28969", "title": "Hydatidiform mole in southern Iran: a statistical survey of 113 cases.", "content": "A statistical review of 113 cases of hydatidiform mole (HM) seen at Pahlavi University Hospital from January 1970 to December 1975 is presented. The incidence of the disease was found to be 1:314 pregnancies. In this study, 73.5% of the patients presumably had acceptable socioeconomic circumstances. The highest incidence of the disease was found in patients 15-25 years old, and it increased with parity. All patients presented with a period of amenorrhea and vaginal spotting. More than 50% of the patients sought treatment after 1-2 weeks of uterine bleeding. Signs and symptoms of the disease are discussed. The management of patients with HM and coexisting difficulties are presented.", "contents": "Hydatidiform mole in southern Iran: a statistical survey of 113 cases. A statistical review of 113 cases of hydatidiform mole (HM) seen at Pahlavi University Hospital from January 1970 to December 1975 is presented. The incidence of the disease was found to be 1:314 pregnancies. In this study, 73.5% of the patients presumably had acceptable socioeconomic circumstances. The highest incidence of the disease was found in patients 15-25 years old, and it increased with parity. All patients presented with a period of amenorrhea and vaginal spotting. More than 50% of the patients sought treatment after 1-2 weeks of uterine bleeding. Signs and symptoms of the disease are discussed. The management of patients with HM and coexisting difficulties are presented."}
{"id": "PMID:28970", "title": "High frequency of hydatidiform mole in native Alaskans.", "content": "The frequency of hydatidiform mole per delivery in the native Alaskan for fiscal years 1969 through 1974 was 1:257. Nutritional studies do not support the suggestion of protein deficiency as an etiologic factor. It is suggested that genetic factors may be involved.", "contents": "High frequency of hydatidiform mole in native Alaskans. The frequency of hydatidiform mole per delivery in the native Alaskan for fiscal years 1969 through 1974 was 1:257. Nutritional studies do not support the suggestion of protein deficiency as an etiologic factor. It is suggested that genetic factors may be involved."}
{"id": "PMID:28971", "title": "Myomectomy in infertile Jamaican women.", "content": "One hundred nineteen Jamaican women who underwent myomectomy from 1964 to 1969 were followed up for 5 to 9 years. Infertility was the most common presenting complaint. Preoperative hysterosalpingograms were performed on 61 patients and were abnormal for the majority of these patients. Surgery revealed submucous fibroids in 41 patients and pelvic inflammatory disease in 51 patients. The pregnancy rate following myomectomy was 18.5%, but successful outcomes occurred in only 9.2% of the cases. Pregnancy was unsuccessful for all patients who underwent both myomectomy and tuboplasty. Twenty-three patients had a recurrence of myoma, and 13 of these underwent subsequent hysterectomy.", "contents": "Myomectomy in infertile Jamaican women. One hundred nineteen Jamaican women who underwent myomectomy from 1964 to 1969 were followed up for 5 to 9 years. Infertility was the most common presenting complaint. Preoperative hysterosalpingograms were performed on 61 patients and were abnormal for the majority of these patients. Surgery revealed submucous fibroids in 41 patients and pelvic inflammatory disease in 51 patients. The pregnancy rate following myomectomy was 18.5%, but successful outcomes occurred in only 9.2% of the cases. Pregnancy was unsuccessful for all patients who underwent both myomectomy and tuboplasty. Twenty-three patients had a recurrence of myoma, and 13 of these underwent subsequent hysterectomy."}
{"id": "PMID:28972", "title": "Unification of a septate uterus: Mahgoub's operation.", "content": "A simple surgical technique for unification of a septate uterus is described. The septum and a small strip of fundus are removed with scissors inserted through two small fundal stabs, and the opening is closed with one mattress suture, which forms an anteroposterior suture line no more than 1 cm long. At the end of the operation an intrauterine contraceptive device is inserted to prevent uterine adhesions. The operation has several advantages: (a) it leaves a capacious uterine cavity of normal appearance, (b) it avoids large uterine incisions, and thus the possibility of postoperative adhesions or weak uterine scars, and (c) it avoids possible injury to the cornual ends of the Fallopian tubes. This article reports favorable results in 17 women treated with this surgical technique.", "contents": "Unification of a septate uterus: Mahgoub's operation. A simple surgical technique for unification of a septate uterus is described. The septum and a small strip of fundus are removed with scissors inserted through two small fundal stabs, and the opening is closed with one mattress suture, which forms an anteroposterior suture line no more than 1 cm long. At the end of the operation an intrauterine contraceptive device is inserted to prevent uterine adhesions. The operation has several advantages: (a) it leaves a capacious uterine cavity of normal appearance, (b) it avoids large uterine incisions, and thus the possibility of postoperative adhesions or weak uterine scars, and (c) it avoids possible injury to the cornual ends of the Fallopian tubes. This article reports favorable results in 17 women treated with this surgical technique."}
{"id": "PMID:28973", "title": "Rupture of the uterus.", "content": "Sixty-four cases of rupture of the uterus were managed from March 1967 to March 1977. The maternal morbidity was 81.0%, and there were six maternal deaths (9.4%). Fifty-two patients (85.5%) had hysterectomies. The average hospital stay for patients who survived was 15.5 days. The fetal mortality rate was 89%. The etiology, diagnostic evaluation and the mode of prevention are discussed.", "contents": "Rupture of the uterus. Sixty-four cases of rupture of the uterus were managed from March 1967 to March 1977. The maternal morbidity was 81.0%, and there were six maternal deaths (9.4%). Fifty-two patients (85.5%) had hysterectomies. The average hospital stay for patients who survived was 15.5 days. The fetal mortality rate was 89%. The etiology, diagnostic evaluation and the mode of prevention are discussed."}
{"id": "PMID:28974", "title": "The present and future of immunologic approaches to contraception.", "content": "A vaccine capable of causing active immunity against one or more key elements of conception would have several advantages over currently available methods of fertility regulation. It would be amenable to mass use, would require only periodic follow-up, and would not require continuous user motivation. Although natural infertility attributable to immunologic factors has been amply documented, the natural mechanism has been only partially delineated. Consequently, researchers trying to develop a workable vaccine are taking various approaches. This report includes a discussion of autoimmune aspermatogenesis, anti-zona pellucida, anti-nonhormonal placenta-specific protein vaccines, and immunization against female and/or early embryonic antigens, including current approaches to the development of an anti-human chorionic gonadotrophin (HCG) vaccine. The potential advantages and disadvantages of the various immunologic methods are discussed, and the author concludes that although the problems associated with present methods of immunologic contraception are substantial they can be resolved.", "contents": "The present and future of immunologic approaches to contraception. A vaccine capable of causing active immunity against one or more key elements of conception would have several advantages over currently available methods of fertility regulation. It would be amenable to mass use, would require only periodic follow-up, and would not require continuous user motivation. Although natural infertility attributable to immunologic factors has been amply documented, the natural mechanism has been only partially delineated. Consequently, researchers trying to develop a workable vaccine are taking various approaches. This report includes a discussion of autoimmune aspermatogenesis, anti-zona pellucida, anti-nonhormonal placenta-specific protein vaccines, and immunization against female and/or early embryonic antigens, including current approaches to the development of an anti-human chorionic gonadotrophin (HCG) vaccine. The potential advantages and disadvantages of the various immunologic methods are discussed, and the author concludes that although the problems associated with present methods of immunologic contraception are substantial they can be resolved."}
{"id": "PMID:28975", "title": "Inducing labor with oral prostaglandin E2 tablets.", "content": "Labor was successfully induced by forewater amniotomy and oral administration of prostaglandin E2 tablets in 91.3% of 153 women with singleton pregnancies. Deliveries occurred within 12 hours for more than 90% of the successfully induced patients. Although not statistically significant, a higher pelvic score appeared to be associated with shorter induction-to-delivery intervals. There were no harmful side effects for either mother or baby; only 14.5% experienced minor side effects, primarily gastrointestinal upsets.", "contents": "Inducing labor with oral prostaglandin E2 tablets. Labor was successfully induced by forewater amniotomy and oral administration of prostaglandin E2 tablets in 91.3% of 153 women with singleton pregnancies. Deliveries occurred within 12 hours for more than 90% of the successfully induced patients. Although not statistically significant, a higher pelvic score appeared to be associated with shorter induction-to-delivery intervals. There were no harmful side effects for either mother or baby; only 14.5% experienced minor side effects, primarily gastrointestinal upsets."}
{"id": "PMID:28976", "title": "Preoperative cervical dilatation with 15(S)15-methyl PGF2alpha methyl ester pessaries.", "content": "A clinical trial comparing two vaginal dose schedules of 15(S)15-methyl prostaglandin F2alpha (PGF2alpha) methyl ester (4 or 6 mg) for preoperative dilatation of the cervix is described. The trial included 28 patients at 8-12 weeks' gestation. Vaginal pessaries containing either 1.0 mg (15 patients) or 1.5 mg (13 patients) of the prostaglandin analogue were administered every 3 hours (maximum, 4 doses). The success rates for the two groups were 93% and 100%, respectively. Sixty percent of the patients aborted before the planned vacuum aspiration. Minor side effects, primarily vomiting and diarrhea, occurred in approximately 80% of the cases and were more prominent with the higher dose pessary. It is concluded that the vaginal administration of 15(S)15-methyl PGF2alpha methyl ester is highly effective for preoperative dilatation of the cervix before suction curettage abortion.", "contents": "Preoperative cervical dilatation with 15(S)15-methyl PGF2alpha methyl ester pessaries. A clinical trial comparing two vaginal dose schedules of 15(S)15-methyl prostaglandin F2alpha (PGF2alpha) methyl ester (4 or 6 mg) for preoperative dilatation of the cervix is described. The trial included 28 patients at 8-12 weeks' gestation. Vaginal pessaries containing either 1.0 mg (15 patients) or 1.5 mg (13 patients) of the prostaglandin analogue were administered every 3 hours (maximum, 4 doses). The success rates for the two groups were 93% and 100%, respectively. Sixty percent of the patients aborted before the planned vacuum aspiration. Minor side effects, primarily vomiting and diarrhea, occurred in approximately 80% of the cases and were more prominent with the higher dose pessary. It is concluded that the vaginal administration of 15(S)15-methyl PGF2alpha methyl ester is highly effective for preoperative dilatation of the cervix before suction curettage abortion."}
{"id": "PMID:28977", "title": "Menstrual regulation in Ibadan, Nigeria.", "content": "Menstrual regulation (MR) (i.e., vacuum aspiration of the uterus with a small diameter, flexible cannula before pregnancy can be determined by a conventional pregnancy test) has been proven safe and effective in many clinics around the world. The present study, which we believe is the first such study of MR in Subsaharan Africa, shows that, for women in an urban African setting, MR is an acceptable backup for other contraceptive methods. Data on 507 MR patients treated at the University College Hospital in Ibadan, Nigeria, between January 1974 and April 1976, showed that the procedure was both safe and effective for 93.4% of the study subjects: there was an overall complication rate of 3.4% and MR failed in seven cases (3.2%). Data also showed that MR is an effective method of recruiting new contraceptive acceptors, as well as an effective back-up procedure in case of contraceptive failure.", "contents": "Menstrual regulation in Ibadan, Nigeria. Menstrual regulation (MR) (i.e., vacuum aspiration of the uterus with a small diameter, flexible cannula before pregnancy can be determined by a conventional pregnancy test) has been proven safe and effective in many clinics around the world. The present study, which we believe is the first such study of MR in Subsaharan Africa, shows that, for women in an urban African setting, MR is an acceptable backup for other contraceptive methods. Data on 507 MR patients treated at the University College Hospital in Ibadan, Nigeria, between January 1974 and April 1976, showed that the procedure was both safe and effective for 93.4% of the study subjects: there was an overall complication rate of 3.4% and MR failed in seven cases (3.2%). Data also showed that MR is an effective method of recruiting new contraceptive acceptors, as well as an effective back-up procedure in case of contraceptive failure."}
{"id": "PMID:28978", "title": "A comparison of metal and plastic cannulae for vacuum aspiration.", "content": "A comparative study of the safety and effectiveness of metal (Purandare) versus plastic (Karman) cannulae for first trimester abortion was conducted on 400 women. Two hundred vacuum aspiration procedures were performed using each type of cannula. All aspirations were performed by a single physician, and patient follow-up was performed by a second physician. The complication rates, amount of retained tissue, rates of cannula obstruction and procedure times of the two cannulae were compared. Our findings showed no significant difference in any of these evaluation criteria for the metal and plastic cannulae.", "contents": "A comparison of metal and plastic cannulae for vacuum aspiration. A comparative study of the safety and effectiveness of metal (Purandare) versus plastic (Karman) cannulae for first trimester abortion was conducted on 400 women. Two hundred vacuum aspiration procedures were performed using each type of cannula. All aspirations were performed by a single physician, and patient follow-up was performed by a second physician. The complication rates, amount of retained tissue, rates of cannula obstruction and procedure times of the two cannulae were compared. Our findings showed no significant difference in any of these evaluation criteria for the metal and plastic cannulae."}
{"id": "PMID:28979", "title": "Second trimester abortion with 5% intraamniotic saline--a pilot study.", "content": "The risk of hypernatremia and related postabortion complications resulting from the intraamniotic administration of a 20-25% hypertonic saline solution, a widely used procedure all over the world, prompted this trial of 5% saline. Midtrimester abortion was induced in 150 women with a 5% saline solution administered intraamniotically at the National Medical College, Calcutta, India, from August 1974 to October 1975. The abortion was complete within 48 hours in 90% of the cases. All the fetuses were delivered dead. In one case, hysterotomy was performed because of severe bleeding. The immediate complication rate was 36% (12% serious). The follow-up complication rate was 2%. One patient died on the seventh postabortal day due to severe, uncontrolled septicemia. The authors conclude that because this procedure is simple and low cost and because it reduces the risk of hypernatremia it should be a welcome addition to service programs in developing countries.", "contents": "Second trimester abortion with 5% intraamniotic saline--a pilot study. The risk of hypernatremia and related postabortion complications resulting from the intraamniotic administration of a 20-25% hypertonic saline solution, a widely used procedure all over the world, prompted this trial of 5% saline. Midtrimester abortion was induced in 150 women with a 5% saline solution administered intraamniotically at the National Medical College, Calcutta, India, from August 1974 to October 1975. The abortion was complete within 48 hours in 90% of the cases. All the fetuses were delivered dead. In one case, hysterotomy was performed because of severe bleeding. The immediate complication rate was 36% (12% serious). The follow-up complication rate was 2%. One patient died on the seventh postabortal day due to severe, uncontrolled septicemia. The authors conclude that because this procedure is simple and low cost and because it reduces the risk of hypernatremia it should be a welcome addition to service programs in developing countries."}
{"id": "PMID:28980", "title": "Hospital counseling in Khartoum: a study of factors affecting contraceptive acceptance after abortion.", "content": "This study examines the impact of contraceptive counseling on 3 263 women hospitalized in Khartoum for treatment of incomplete abortion. The analysis which focused on education and parity/child desire, revealed that the counseling program produced contraceptive acceptance among 47.0% of those followed up. In spite of the counseling efforts, half of the women in this study did not accept contraception following the abortion-regardless of education or parity/child desire. It is difficult to determine why 50% of those who had recently undergone an incomplete abortion were willing to put themselves at risk again. Apparently, future efforts to increase the impact of counseling programs must also examine patients' motivation to accept (or not to accept) contraception.", "contents": "Hospital counseling in Khartoum: a study of factors affecting contraceptive acceptance after abortion. This study examines the impact of contraceptive counseling on 3 263 women hospitalized in Khartoum for treatment of incomplete abortion. The analysis which focused on education and parity/child desire, revealed that the counseling program produced contraceptive acceptance among 47.0% of those followed up. In spite of the counseling efforts, half of the women in this study did not accept contraception following the abortion-regardless of education or parity/child desire. It is difficult to determine why 50% of those who had recently undergone an incomplete abortion were willing to put themselves at risk again. Apparently, future efforts to increase the impact of counseling programs must also examine patients' motivation to accept (or not to accept) contraception."}
{"id": "PMID:28981", "title": "Advances in sterilization equipment.", "content": "From the array of sterilization procedures that are safe, simple and effective, the service provider must select procedures that fit his or her logistical criteria, which include the cost and maintenance of equipment, availability of supplies, and training of the requisite personnel. In this paper, these criteria are discussed for each of the various sterilization procedures. Information about female sterilization equipment for conventional postpartum laparotomy, minilaparotomy, colpotomy, laparoscopy, and culdoscopy is presented, together with facts about the related tubal occlusion techniques. The standard ligation techniques for male sterilization are compared with the newer electrocoagulation and thermocoagulation methods. A variety of methods for both female and male sterilization that are in the research stage are also mentioned. It is concluded that, from a programmatic point of view, vasectomy and postpartum ligation via laparotomy are the optimal sterilization procedures. For women who have not recently been pregnant, minilaparotomy with a standard tubal ligation technique is recommended, except in large teaching hospitals where laparoscopy can be performed efficiently.", "contents": "Advances in sterilization equipment. From the array of sterilization procedures that are safe, simple and effective, the service provider must select procedures that fit his or her logistical criteria, which include the cost and maintenance of equipment, availability of supplies, and training of the requisite personnel. In this paper, these criteria are discussed for each of the various sterilization procedures. Information about female sterilization equipment for conventional postpartum laparotomy, minilaparotomy, colpotomy, laparoscopy, and culdoscopy is presented, together with facts about the related tubal occlusion techniques. The standard ligation techniques for male sterilization are compared with the newer electrocoagulation and thermocoagulation methods. A variety of methods for both female and male sterilization that are in the research stage are also mentioned. It is concluded that, from a programmatic point of view, vasectomy and postpartum ligation via laparotomy are the optimal sterilization procedures. For women who have not recently been pregnant, minilaparotomy with a standard tubal ligation technique is recommended, except in large teaching hospitals where laparoscopy can be performed efficiently."}
{"id": "PMID:28982", "title": "Laparoscopic electrocoagulation and tubal ring techniques for sterilization: a comparative study.", "content": "From August 1975 through May 1976, a comparative study was made of the effects of sterilization by standard electrocoagulation and tubal ring application techniques. The two techniques were randomly assigned to 300 patients. Results show that standard electrocoagulation and tubal ring procedures can easily and safely be performed on an outpatient basis, using local anesthetics and analgesics. Rates of surgical complications for both techniques were clinically acceptable, although tubal risk patients had a higher rate. Pain during the procedure and during the immediate recovery period was more severe for tubal ring patients. Despite the higher incidence of surgical complications and pain associated with the ring, many physicians prefer this method of sterilization because it eliminates the possibility, inherent in electrocoagulation, of inadvertent serious electrical burns.", "contents": "Laparoscopic electrocoagulation and tubal ring techniques for sterilization: a comparative study. From August 1975 through May 1976, a comparative study was made of the effects of sterilization by standard electrocoagulation and tubal ring application techniques. The two techniques were randomly assigned to 300 patients. Results show that standard electrocoagulation and tubal ring procedures can easily and safely be performed on an outpatient basis, using local anesthetics and analgesics. Rates of surgical complications for both techniques were clinically acceptable, although tubal risk patients had a higher rate. Pain during the procedure and during the immediate recovery period was more severe for tubal ring patients. Despite the higher incidence of surgical complications and pain associated with the ring, many physicians prefer this method of sterilization because it eliminates the possibility, inherent in electrocoagulation, of inadvertent serious electrical burns."}
{"id": "PMID:28983", "title": "Training physicians of developing nations in female surgical contraception.", "content": "The majority of developing nations in the Third World (including Thailand) face similar medicosocioeconomic situations arising from uncontrolled population growth which outstrips developmental planning. One of the most effective medical means of combating these problems is surgical contraception. This study describes how the Ramathibodi National Training Program was developed and implemented in Thailand to increase the availability of sterilization services by training local physicians to perform the necessary operations. The success of this program is measured by the increase in the number of service delivery stations (182) and in the number of sterilization procedures performed (24 436 in a 32-month period).", "contents": "Training physicians of developing nations in female surgical contraception. The majority of developing nations in the Third World (including Thailand) face similar medicosocioeconomic situations arising from uncontrolled population growth which outstrips developmental planning. One of the most effective medical means of combating these problems is surgical contraception. This study describes how the Ramathibodi National Training Program was developed and implemented in Thailand to increase the availability of sterilization services by training local physicians to perform the necessary operations. The success of this program is measured by the increase in the number of service delivery stations (182) and in the number of sterilization procedures performed (24 436 in a 32-month period)."}
{"id": "PMID:28984", "title": "The water and nitrogen composition of the placenta in anemic women.", "content": "A study was conducted to determine the water and nitrogen content of the placentae from anemic and nonanemic Nigerian women. The mean water content values were 84.9% and 85.3%, respectively, and this difference was not statistically significant. Placental nitrogen values were higher in anemic women than they were in nonanemic women, but the difference was not statistically significant. The results of this study indicate that placental hypertrophy which is associated with anemia is not due to water retention by the placenta.", "contents": "The water and nitrogen composition of the placenta in anemic women. A study was conducted to determine the water and nitrogen content of the placentae from anemic and nonanemic Nigerian women. The mean water content values were 84.9% and 85.3%, respectively, and this difference was not statistically significant. Placental nitrogen values were higher in anemic women than they were in nonanemic women, but the difference was not statistically significant. The results of this study indicate that placental hypertrophy which is associated with anemia is not due to water retention by the placenta."}
{"id": "PMID:28986", "title": "Effects of x-ray on a gravida with severe hemoconcentration: a case report.", "content": "A gravida with severe hemoconcentration was studied with intravenous urography because of right upper quadrant pain. She subsequently developed renal failure. The potential hazard of urography in the presence of a severe blood volume contraction state is noted.", "contents": "Effects of x-ray on a gravida with severe hemoconcentration: a case report. A gravida with severe hemoconcentration was studied with intravenous urography because of right upper quadrant pain. She subsequently developed renal failure. The potential hazard of urography in the presence of a severe blood volume contraction state is noted."}
{"id": "PMID:28987", "title": "Coarctation of the umbilical cord: a cause of intrauterine fetal death.", "content": "This article presents 16 cases of coarctation of the umbilical cord, resulting in fetal death in utero in pregnant women of more than 6 months' gestation. Coarctation of the umbilical cord can occur in any phase of the gestational period and is not related to parity. The stricture of the cord is usually accompanied by torsion and characterized by a fibrosis of the Wharton's jelly and a thickening of the vascular walls which obstructs the fetoplacental circulation, leading to anoxia and fetal death. Although this entity must occur frequently, it is not often reported by obstetricians because the umbilical cord is not carefully examined in all cases of stillbirth.", "contents": "Coarctation of the umbilical cord: a cause of intrauterine fetal death. This article presents 16 cases of coarctation of the umbilical cord, resulting in fetal death in utero in pregnant women of more than 6 months' gestation. Coarctation of the umbilical cord can occur in any phase of the gestational period and is not related to parity. The stricture of the cord is usually accompanied by torsion and characterized by a fibrosis of the Wharton's jelly and a thickening of the vascular walls which obstructs the fetoplacental circulation, leading to anoxia and fetal death. Although this entity must occur frequently, it is not often reported by obstetricians because the umbilical cord is not carefully examined in all cases of stillbirth."}
{"id": "PMID:28988", "title": "Controlled assessment of oral bronchodilators for asthmatic children.", "content": "Various pulmonary function changes were determined in twenty paediatric patients after a single oral dose of theophylline, ephedrine, or their combination in a double-blind crossover study. The possible contributions of guaifenesin and butabarbital, components of some formulations in clinical use, were also examined. Bronchodilatory efficacy in decreasing order, when compared to placebo, was observed for theophylline-ephedrine and theophylline (nearly comparable), and for ephedrine-butabarbital and ephedrine (nearly comparable). Butabarbital and guaifenesin did not enhance or decrease bronchodilatory effect. Adverse reactions appeared to be more frequently related to ephedrine intake, although no serious reactions were noted.", "contents": "Controlled assessment of oral bronchodilators for asthmatic children. Various pulmonary function changes were determined in twenty paediatric patients after a single oral dose of theophylline, ephedrine, or their combination in a double-blind crossover study. The possible contributions of guaifenesin and butabarbital, components of some formulations in clinical use, were also examined. Bronchodilatory efficacy in decreasing order, when compared to placebo, was observed for theophylline-ephedrine and theophylline (nearly comparable), and for ephedrine-butabarbital and ephedrine (nearly comparable). Butabarbital and guaifenesin did not enhance or decrease bronchodilatory effect. Adverse reactions appeared to be more frequently related to ephedrine intake, although no serious reactions were noted."}
{"id": "PMID:28989", "title": "Comparative efficacy of triazolam, flurazepam and placebo in out-patients insomniacs.", "content": "The short-term hypnotic efficacy of triazolam was compared to that of flurazepam and placebo in 120 out-patient insomniacs. Each patient was studied with a two-night, double-blind crossover trial. Triazolam (0.5 mg) was compared to placebo and flurazepam (30 mg). Triazolam (0.25 mg) was compared to flurazepam (15 mg and 30 mg). Triazolam (0.5 mg) was preferred to both placebo and flurazepam (30 mg). Triazolam (0.5 mg) was superior to placebo in improving quality of sleep, shortening sleep onset, increasing sleep duration, and reducing the number of night-time awakenings. Triazolam (0.5 mg) was superior to flurazepam (30 mg) in speeding sleep onset and increasing the quality of sleep. Triazolam (0.25 mg) was preferred to flurazepam (15 mg) and was significantly better than flurazepam on all sleep questions. Triazolam (0.25 mg) was preferred by more patients than flurazepam (30 mg) and was judged equally efficacious on individual sleep questions. Reports of side-effects were minimal for both drugs.", "contents": "Comparative efficacy of triazolam, flurazepam and placebo in out-patients insomniacs. The short-term hypnotic efficacy of triazolam was compared to that of flurazepam and placebo in 120 out-patient insomniacs. Each patient was studied with a two-night, double-blind crossover trial. Triazolam (0.5 mg) was compared to placebo and flurazepam (30 mg). Triazolam (0.25 mg) was compared to flurazepam (15 mg and 30 mg). Triazolam (0.5 mg) was preferred to both placebo and flurazepam (30 mg). Triazolam (0.5 mg) was superior to placebo in improving quality of sleep, shortening sleep onset, increasing sleep duration, and reducing the number of night-time awakenings. Triazolam (0.5 mg) was superior to flurazepam (30 mg) in speeding sleep onset and increasing the quality of sleep. Triazolam (0.25 mg) was preferred to flurazepam (15 mg) and was significantly better than flurazepam on all sleep questions. Triazolam (0.25 mg) was preferred by more patients than flurazepam (30 mg) and was judged equally efficacious on individual sleep questions. Reports of side-effects were minimal for both drugs."}
{"id": "PMID:28990", "title": "A clinical comparison of triazolam with placebo and with secobarbital in insomniac patients.", "content": "Seventy-six out-patient insomniacs participated in three different two-night, double-blind crossover trials investigating the hypnotic efficacy andsafety of triazolam. Triazolam 0.5 mg was compared to placebo in one trial conducted K Kay Okawa, MD, and triazolam 0.5 mg was compared to secobarbital 100 mg in trials conducted by K Kay Okawa, MD and George S Allen, MD. The results of the later two studies were combined and the data analyzed jointly. Triazolam 0.5 mg was found to be preferred and to be significantly better than both placebo and secobarbital 100 mg in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to either placebo or secobarbital on the following parameters: how much the medication helped the patients sleep; onset of sleep; duration of sleep; and number of nocturnal awakenings. No differences were observed between treatments in any trial with regard to the patient's feeling of alertness the next morning. The side-effects reported for all treatments did not significantly interfere with the patient's ability to function.", "contents": "A clinical comparison of triazolam with placebo and with secobarbital in insomniac patients. Seventy-six out-patient insomniacs participated in three different two-night, double-blind crossover trials investigating the hypnotic efficacy andsafety of triazolam. Triazolam 0.5 mg was compared to placebo in one trial conducted K Kay Okawa, MD, and triazolam 0.5 mg was compared to secobarbital 100 mg in trials conducted by K Kay Okawa, MD and George S Allen, MD. The results of the later two studies were combined and the data analyzed jointly. Triazolam 0.5 mg was found to be preferred and to be significantly better than both placebo and secobarbital 100 mg in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to either placebo or secobarbital on the following parameters: how much the medication helped the patients sleep; onset of sleep; duration of sleep; and number of nocturnal awakenings. No differences were observed between treatments in any trial with regard to the patient's feeling of alertness the next morning. The side-effects reported for all treatments did not significantly interfere with the patient's ability to function."}
{"id": "PMID:28998", "title": "Arbovirus isolations from mosquitoes in South Slovakia.", "content": "In the years 1973 and 1975 mosquitoes and some other Diptera (Tabanidae, Simuliidae, Hippoboscidae) were tested for virus. 13,924 mosquitoes, 75 horseflies and 60 blackflies were processed in 1973. Five strains of Tahyna virus were isolated from mosquito species Aedes vexans. 3,378 mosquitoes and 12 sheep keds were tested for virus in 1975. Twelve strains of Calovo virus were isolated from Anopheles maculipennis and one strain of Tahyna virus was obtained from Aedes vexans mosquitoes.", "contents": "Arbovirus isolations from mosquitoes in South Slovakia. In the years 1973 and 1975 mosquitoes and some other Diptera (Tabanidae, Simuliidae, Hippoboscidae) were tested for virus. 13,924 mosquitoes, 75 horseflies and 60 blackflies were processed in 1973. Five strains of Tahyna virus were isolated from mosquito species Aedes vexans. 3,378 mosquitoes and 12 sheep keds were tested for virus in 1975. Twelve strains of Calovo virus were isolated from Anopheles maculipennis and one strain of Tahyna virus was obtained from Aedes vexans mosquitoes."}
{"id": "PMID:29003", "title": "Chinese health system gets down to basics.", "content": "Preventive medicine and primary health care, rather than advanced medical technology, appear to be the focus of health care delivery in China. In fact, the author says, one could imagine a decision being made not to install a CT scanner so that more physician extenders could be trained to improve nutritional standards, help eliminate infectious diseases, and provide health education information to people who would not otherwise be exposed to these services.", "contents": "Chinese health system gets down to basics. Preventive medicine and primary health care, rather than advanced medical technology, appear to be the focus of health care delivery in China. In fact, the author says, one could imagine a decision being made not to install a CT scanner so that more physician extenders could be trained to improve nutritional standards, help eliminate infectious diseases, and provide health education information to people who would not otherwise be exposed to these services."}
{"id": "PMID:29004", "title": "Identification of a new serum protein polymorphism as transferrin.", "content": "By isoelectric focusing at pH 3.5--9.5, K\u00fchnl and Spielmann (1977) recently demonstrated a new genetically determined serum protein polymorphism designated 'Hpa' because of an apparently specific reaction with antihaptoglobin. In this study the polymorphism was reproduced, but the components were found to focus at pH 5.8, which is different from the pI of haptoglobin, and immunologic relation to haptoglobin could not be confirmed. Using pure transferrin as a reference, the results of isoelectric focusing, crossed immunoelectrophoresis, and immunofixation indicated that the polymorphic components were identical to transferrin. This polymorphism does not correspond to the already known transferrin polymorphism, as the two usual genes, tentatively designated Tf1 and Tf2, in my population sample (n = 132) were 0.19 and 0.81, and, further, all individuals except three in the sample belong to type Tf-C.", "contents": "Identification of a new serum protein polymorphism as transferrin. By isoelectric focusing at pH 3.5--9.5, K\u00fchnl and Spielmann (1977) recently demonstrated a new genetically determined serum protein polymorphism designated 'Hpa' because of an apparently specific reaction with antihaptoglobin. In this study the polymorphism was reproduced, but the components were found to focus at pH 5.8, which is different from the pI of haptoglobin, and immunologic relation to haptoglobin could not be confirmed. Using pure transferrin as a reference, the results of isoelectric focusing, crossed immunoelectrophoresis, and immunofixation indicated that the polymorphic components were identical to transferrin. This polymorphism does not correspond to the already known transferrin polymorphism, as the two usual genes, tentatively designated Tf1 and Tf2, in my population sample (n = 132) were 0.19 and 0.81, and, further, all individuals except three in the sample belong to type Tf-C."}
{"id": "PMID:29005", "title": "Preparation and long-term cultivation of porcine tracheal and lung organ cultures by alternate exposure to gaseous and liquid medium phases.", "content": "Conventional methods of organ culture have proved unsatisfactory for mammalian lung because of the rapid collapse of the tissue and the loss of its normal structure. In an effort to circumvent this problem and to provide a means for visualizing the cellular relationships throughout the culture period, respiratory organs consisting of trachea and lungs of fetal or hysterectomy-derived 1- to 4-week-old pigs were embedded in warm 3% Noble agar in phosphate buffer silicone solution and cooled to firmness. By use of a described cutting device, the respective organs were sliced into thin, 0.5- to 1.0-mm tracheal ring or lung explants. These organ sections then were cultured by exposure to alternate gaseous and liquid-medium phases by rotation (12 rev per hr) in sealed Leighton tubes fitted in a described rotator. In short-,erm culture experiments, explants were best maintained in a culture-support medium containing Eagle's minimal essential medium, 20% fetal bovine serum, 0.5% lactalbumin hydrolysate, and other supplements in a pH range of 6.5 to 8.2, and a NaCl concentration of 0.1 M or less. By bright-field and scanning-electron microscopy, tracheal ring and lung explant cultures incubated for 2 months showed intact, uniform and active ciliated epithelial surfaces which compared favorably with those of fresh preparations. The lung cultures showed alveoli that remained expanded, and the cellular integrity of the tissues remained normal in appearance. This new method provides respiratory organs as continuous records with exceptional cellular clarity and readily available for histological processing. The organ cultures lend themselves well to pathogenesis studies in which subtle cellualr changes or a sequence of changes induced in pulmonary tissues are difficult to observe in the host.", "contents": "Preparation and long-term cultivation of porcine tracheal and lung organ cultures by alternate exposure to gaseous and liquid medium phases. Conventional methods of organ culture have proved unsatisfactory for mammalian lung because of the rapid collapse of the tissue and the loss of its normal structure. In an effort to circumvent this problem and to provide a means for visualizing the cellular relationships throughout the culture period, respiratory organs consisting of trachea and lungs of fetal or hysterectomy-derived 1- to 4-week-old pigs were embedded in warm 3% Noble agar in phosphate buffer silicone solution and cooled to firmness. By use of a described cutting device, the respective organs were sliced into thin, 0.5- to 1.0-mm tracheal ring or lung explants. These organ sections then were cultured by exposure to alternate gaseous and liquid-medium phases by rotation (12 rev per hr) in sealed Leighton tubes fitted in a described rotator. In short-,erm culture experiments, explants were best maintained in a culture-support medium containing Eagle's minimal essential medium, 20% fetal bovine serum, 0.5% lactalbumin hydrolysate, and other supplements in a pH range of 6.5 to 8.2, and a NaCl concentration of 0.1 M or less. By bright-field and scanning-electron microscopy, tracheal ring and lung explant cultures incubated for 2 months showed intact, uniform and active ciliated epithelial surfaces which compared favorably with those of fresh preparations. The lung cultures showed alveoli that remained expanded, and the cellular integrity of the tissues remained normal in appearance. This new method provides respiratory organs as continuous records with exceptional cellular clarity and readily available for histological processing. The organ cultures lend themselves well to pathogenesis studies in which subtle cellualr changes or a sequence of changes induced in pulmonary tissues are difficult to observe in the host."}
{"id": "PMID:29007", "title": "Adherence of Mycoplasma gallisepticum to human erythrocytes.", "content": "Pathogenic mycoplasmas adhere to and colonize the epithelial lining of the respiratory and genital tracts of infected animals. An experimental system suitable for the quantitative study of mycoplasma adherence has been developed by us. The system consists of human erythrocytes (RBC) and the avian pathogen Mycoplasma gallisepticum, in which membrane lipids were labeled. The amount of mycoplasma cells attached to the RBC, which was determined according to radioactivity measurements, decreased on increasing the pH or ionic strength of the attachment mixture. Attachment followed first-order kinetics and depended on temperature. The mycoplasma cell population remaining in the supernatant fluid after exposure to RBC showed a much poorer ability to attach to RBC during a second attachment test, indicating an unequal distribution of binding sites among cells within a given population. The gradual removal of sialic acid residues from the RBC by neuraminidase was accompanied by a decrease in mycoplasma attachment. Isolated glycophorin, the RBC membrane glycoprotein carrying almost all the sialic acid moieties of the RBC, inhibited M. gallisepticum attachment, whereas asialoglycophorin and sialic acid itself were very poor inhibitors of attachment. Only part of the (125)I-labeled glycophorin bound to mycoplasmas could be removed by neuraminidase or by exchange with unlabeled glycophorin. It is suggested that glycophorin, representing the isolated major RBC receptor for M. gallisepticum, binds to the mycoplasmas both specifically, through its sialic acid moieties, and nonspecifically, through its exposed hydrophobic polypeptide moiety.", "contents": "Adherence of Mycoplasma gallisepticum to human erythrocytes. Pathogenic mycoplasmas adhere to and colonize the epithelial lining of the respiratory and genital tracts of infected animals. An experimental system suitable for the quantitative study of mycoplasma adherence has been developed by us. The system consists of human erythrocytes (RBC) and the avian pathogen Mycoplasma gallisepticum, in which membrane lipids were labeled. The amount of mycoplasma cells attached to the RBC, which was determined according to radioactivity measurements, decreased on increasing the pH or ionic strength of the attachment mixture. Attachment followed first-order kinetics and depended on temperature. The mycoplasma cell population remaining in the supernatant fluid after exposure to RBC showed a much poorer ability to attach to RBC during a second attachment test, indicating an unequal distribution of binding sites among cells within a given population. The gradual removal of sialic acid residues from the RBC by neuraminidase was accompanied by a decrease in mycoplasma attachment. Isolated glycophorin, the RBC membrane glycoprotein carrying almost all the sialic acid moieties of the RBC, inhibited M. gallisepticum attachment, whereas asialoglycophorin and sialic acid itself were very poor inhibitors of attachment. Only part of the (125)I-labeled glycophorin bound to mycoplasmas could be removed by neuraminidase or by exchange with unlabeled glycophorin. It is suggested that glycophorin, representing the isolated major RBC receptor for M. gallisepticum, binds to the mycoplasmas both specifically, through its sialic acid moieties, and nonspecifically, through its exposed hydrophobic polypeptide moiety."}
{"id": "PMID:29008", "title": "Increased susceptibility of splenectomized mice to infection after exposure to an aerosolized suspension of type III Streptococcus pneumoniae.", "content": "Most reported experimental studies concerning the effect of splenectomy in animals have shown enhanced mortality from pneumococci injected either intravenously or intraperitoneally. We have developed a laboratory model in which mice are exposed to type III Streptococcus pneumoniae via an aerosolized atmosphere, thus closely approximating the route of human infection with this organism. Ninety-one male Swiss mice (mean weight 26 g) were divided into three approximately equal groups of control, sham-operated, and splenectomized animals. Two weeks later they were exposed for 30 min in individualized compartments within a confined chamber to an aerosolized atmosphere producing a uniform challenge of 5.9 X 10(9) colony-forming units per ml of pneumococci. A statistically significant increase (P less than 0.01) in mortality was demonstrated in the splenectomized group over the pooled sham-operated and control groups. The animal model used in these investigations can be applied to the study of infections acquired by the respiratory route in numerous experimental designs.", "contents": "Increased susceptibility of splenectomized mice to infection after exposure to an aerosolized suspension of type III Streptococcus pneumoniae. Most reported experimental studies concerning the effect of splenectomy in animals have shown enhanced mortality from pneumococci injected either intravenously or intraperitoneally. We have developed a laboratory model in which mice are exposed to type III Streptococcus pneumoniae via an aerosolized atmosphere, thus closely approximating the route of human infection with this organism. Ninety-one male Swiss mice (mean weight 26 g) were divided into three approximately equal groups of control, sham-operated, and splenectomized animals. Two weeks later they were exposed for 30 min in individualized compartments within a confined chamber to an aerosolized atmosphere producing a uniform challenge of 5.9 X 10(9) colony-forming units per ml of pneumococci. A statistically significant increase (P less than 0.01) in mortality was demonstrated in the splenectomized group over the pooled sham-operated and control groups. The animal model used in these investigations can be applied to the study of infections acquired by the respiratory route in numerous experimental designs."}
{"id": "PMID:29009", "title": "Respiration and oxidative phosphorylation in Treponema pallidum.", "content": "Exogenous and endogenously generated reduced pyridine nucleotides caused marked stimulation of O(2) uptake when added to treponemal cell-free extracts, which indicated that terminal electron transport was coupled to the consumption of O(2). Oxidation of reduced nicotinamide adenine dinucleotide (NADH) was shown to correlate stoichiometrically with O(2) reduction, suggesting that NADH was being oxidized through a mainstream respiratory chain dehydrogenase. Oxygen evolution in treponemal extracts was observed after the completion of O(2) uptake which was stimulated by exogenous NADH and endogenously generated reduced NAD phosphate. Oxygen evolution was inhibited by both cyanide and pyruvate, which was consistent with O(2) release from H(2)O(2) by catalase. The addition of exogenous H(2)O(2) to treponemal extracts caused rapid O(2) evolution characteristic of a catalase reaction. A spectrophotometric assay was used to measure ATP formation in T. pallidum cell-free extracts that were stimulated with NADH. P/O ratios from 0.5 to 1.1 were calculated from the amounts of ATP formed versus NADH oxidized. Phosphorylating activity was dependent on P(i) concentration and was sensitive to cyanide, N, N'-dicyclohexylcarbodiimide, and carbonyl cyanide m-chlorophenyl hydrazone. Adenine nucleotide pools of T. pallidum were measured by the firefly luciferin-luciferase assay. Shifts in adenine nucleotide levels upon the addition of NADH to cell-free extracts were impossible to evaluate due to the presence of NAD(+) nucleosidase. However, when whole cells, previously incubated under an atmosphere of 95% N(2)-5% CO(2), were sparged with air, ATP and ADP levels increased, while AMP levels decreased. The shift was attributed to both oxidative phosphorylation and to the presence of an adenylate kinase activity. T. pallidum was also found to possess an Mg(2+) - and Ca(2+) -stimulated ATPase activity which was sensitive to N, N' -dicyclohexylcarbodiimide. These data indicated a capability for oxidative phosphorylation by T. pallidum.", "contents": "Respiration and oxidative phosphorylation in Treponema pallidum. Exogenous and endogenously generated reduced pyridine nucleotides caused marked stimulation of O(2) uptake when added to treponemal cell-free extracts, which indicated that terminal electron transport was coupled to the consumption of O(2). Oxidation of reduced nicotinamide adenine dinucleotide (NADH) was shown to correlate stoichiometrically with O(2) reduction, suggesting that NADH was being oxidized through a mainstream respiratory chain dehydrogenase. Oxygen evolution in treponemal extracts was observed after the completion of O(2) uptake which was stimulated by exogenous NADH and endogenously generated reduced NAD phosphate. Oxygen evolution was inhibited by both cyanide and pyruvate, which was consistent with O(2) release from H(2)O(2) by catalase. The addition of exogenous H(2)O(2) to treponemal extracts caused rapid O(2) evolution characteristic of a catalase reaction. A spectrophotometric assay was used to measure ATP formation in T. pallidum cell-free extracts that were stimulated with NADH. P/O ratios from 0.5 to 1.1 were calculated from the amounts of ATP formed versus NADH oxidized. Phosphorylating activity was dependent on P(i) concentration and was sensitive to cyanide, N, N'-dicyclohexylcarbodiimide, and carbonyl cyanide m-chlorophenyl hydrazone. Adenine nucleotide pools of T. pallidum were measured by the firefly luciferin-luciferase assay. Shifts in adenine nucleotide levels upon the addition of NADH to cell-free extracts were impossible to evaluate due to the presence of NAD(+) nucleosidase. However, when whole cells, previously incubated under an atmosphere of 95% N(2)-5% CO(2), were sparged with air, ATP and ADP levels increased, while AMP levels decreased. The shift was attributed to both oxidative phosphorylation and to the presence of an adenylate kinase activity. T. pallidum was also found to possess an Mg(2+) - and Ca(2+) -stimulated ATPase activity which was sensitive to N, N' -dicyclohexylcarbodiimide. These data indicated a capability for oxidative phosphorylation by T. pallidum."}
{"id": "PMID:29015", "title": "The application of covert conditioning procedures to the outpatient treatment of drug addicts: four case studies.", "content": "The purpose of this study was to determine the effectiveness of covert conditioning procedures in the outpatient treatment of drug addicts who wished to decrease or cease use of drugs. A desensitization design proved unsuccessful in reducing craving in an opiate user with a 2-year history of abuse. Three sensitization designs with addicts who had abused opiates from 2 to 13 years produced no more than a temporary decrease in drug craving or taking. Although there appeared to be some potency in the application of covert aversive counterconditioning and mixed aversive conditioning, the procedures were not capable of producing an enduring decrease in drug craving or taking in any of the subjects. Problems in the outpatient treatment of drug addicts using covert conditioning procedures are discussed. Recommendations for further study are made, with an emphasis on use of a multiform approach.", "contents": "The application of covert conditioning procedures to the outpatient treatment of drug addicts: four case studies. The purpose of this study was to determine the effectiveness of covert conditioning procedures in the outpatient treatment of drug addicts who wished to decrease or cease use of drugs. A desensitization design proved unsuccessful in reducing craving in an opiate user with a 2-year history of abuse. Three sensitization designs with addicts who had abused opiates from 2 to 13 years produced no more than a temporary decrease in drug craving or taking. Although there appeared to be some potency in the application of covert aversive counterconditioning and mixed aversive conditioning, the procedures were not capable of producing an enduring decrease in drug craving or taking in any of the subjects. Problems in the outpatient treatment of drug addicts using covert conditioning procedures are discussed. Recommendations for further study are made, with an emphasis on use of a multiform approach."}
{"id": "PMID:29016", "title": "A comparative study of three different citrate combinations of litholytic action.", "content": "Three different combinations--the Eisenberg solution, Uralyt-U and Magurlit--have been compared for their litholytic effect on urate calculi in a homogeneous patient material. Magurlit and Uralyt-U have been found superior to the Eisenberg solution, insofar as they are dispensed in a hygienic form easy to handle and require for the production of the litholytic pH levels a shorter time than does the Eisenberg solution. In opposition to other citrate combinations, Magurlit may be used with success even if the urate calculus contain an additional component, unless its distribution is unfavourable and its proportion exceeds 15 to 20%.", "contents": "A comparative study of three different citrate combinations of litholytic action. Three different combinations--the Eisenberg solution, Uralyt-U and Magurlit--have been compared for their litholytic effect on urate calculi in a homogeneous patient material. Magurlit and Uralyt-U have been found superior to the Eisenberg solution, insofar as they are dispensed in a hygienic form easy to handle and require for the production of the litholytic pH levels a shorter time than does the Eisenberg solution. In opposition to other citrate combinations, Magurlit may be used with success even if the urate calculus contain an additional component, unless its distribution is unfavourable and its proportion exceeds 15 to 20%."}
{"id": "PMID:29017", "title": "Antibiotics excretion in canine vaginal and urethral secretions.", "content": "Trimethroprim, erythromycin, ampicillin, and rosamicin, a new macrolide antibiotic, were administered to dogs by constant intravenous infusion. Their concentrations in plasma, urine, vaginal and urethral secretions, saliva, and tears were determined by bioassay. Trimethoprim, rosamicin, and, to a lower degree, erythromycin were concentrated in the secretions of the vagina and the urethra whereas the ampicillin concentrations in these secretions never exceeded the simultaneous plasma concentrations. Inasmuch as rosamicin and trimethoprim have antibacterial spectra well suited for the treatment of bacterial urethritis and vaginitis they should be investigated clinically in this respect.", "contents": "Antibiotics excretion in canine vaginal and urethral secretions. Trimethroprim, erythromycin, ampicillin, and rosamicin, a new macrolide antibiotic, were administered to dogs by constant intravenous infusion. Their concentrations in plasma, urine, vaginal and urethral secretions, saliva, and tears were determined by bioassay. Trimethoprim, rosamicin, and, to a lower degree, erythromycin were concentrated in the secretions of the vagina and the urethra whereas the ampicillin concentrations in these secretions never exceeded the simultaneous plasma concentrations. Inasmuch as rosamicin and trimethoprim have antibacterial spectra well suited for the treatment of bacterial urethritis and vaginitis they should be investigated clinically in this respect."}
{"id": "PMID:29020", "title": "NADP-dependent dehydrogenases in rat liver parenchyma. I. Methodological studies on the qualitative histochemistry of G6PDH, 6PGDH, malic enzyme and ICDH.", "content": "At present soluble NADP-dependent dehydrogenases are histochemically demonstrated in three different ways: according to the standard method incubation in aqueous media leads to the precipitation of formazan, the formation of which depends entirely on the presence of endogeneous NADPH2-tetrazolium reductases. With the two more recently established methods these reductases are by-passed with the use of intermediate electron acceptors incorporated in the medium. In addition, enzyme diffusion is inhibited either by an increased viscosity of the medium (PVA) or by a semipermeable membrane separating the medium from the section. Depending on the technique applied different distribution patterns have been described. By altering the concentrations of substrates, coenzyme, tetrazolium salt and cytochrome oxidase inhibitor, it was possible to improve both the PVA and membrane methods. Although similar results were obtained, because of its advantages the PVA method is recommended in this report and a detailed description is given. Using the latter for the demonstration of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDH), characteristic distribution patterns were obtained in the liver parenchyma of male and female rats. For the first time a high G6PDH activity could be demonstrated in nonparenchymal cells which are mainly found in zone 1 of the liver acinus.", "contents": "NADP-dependent dehydrogenases in rat liver parenchyma. I. Methodological studies on the qualitative histochemistry of G6PDH, 6PGDH, malic enzyme and ICDH. At present soluble NADP-dependent dehydrogenases are histochemically demonstrated in three different ways: according to the standard method incubation in aqueous media leads to the precipitation of formazan, the formation of which depends entirely on the presence of endogeneous NADPH2-tetrazolium reductases. With the two more recently established methods these reductases are by-passed with the use of intermediate electron acceptors incorporated in the medium. In addition, enzyme diffusion is inhibited either by an increased viscosity of the medium (PVA) or by a semipermeable membrane separating the medium from the section. Depending on the technique applied different distribution patterns have been described. By altering the concentrations of substrates, coenzyme, tetrazolium salt and cytochrome oxidase inhibitor, it was possible to improve both the PVA and membrane methods. Although similar results were obtained, because of its advantages the PVA method is recommended in this report and a detailed description is given. Using the latter for the demonstration of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDH), characteristic distribution patterns were obtained in the liver parenchyma of male and female rats. For the first time a high G6PDH activity could be demonstrated in nonparenchymal cells which are mainly found in zone 1 of the liver acinus."}
{"id": "PMID:29021", "title": "Isoelectric focusing studies on the neutral 5'-nucleotidase from Wistar rat hippocampus: evidence for the absence of isoenzymes.", "content": "The pattern and some substrates characteristic of the rat brain 5'-nucleotidase were studied using the isoelectric focusing technique, which revealed that the enzyme is present in a single form in hippocampus extracts. An alkaline phosphatase, which is also able to split nucleoside monophosphates, is not active at neutral pH values. The isoelectric points were found to be 6.4 +/- 0.1 for the specific 5'-nucleotidase and 6.8 +/- 0.1 for the phosphatase.", "contents": "Isoelectric focusing studies on the neutral 5'-nucleotidase from Wistar rat hippocampus: evidence for the absence of isoenzymes. The pattern and some substrates characteristic of the rat brain 5'-nucleotidase were studied using the isoelectric focusing technique, which revealed that the enzyme is present in a single form in hippocampus extracts. An alkaline phosphatase, which is also able to split nucleoside monophosphates, is not active at neutral pH values. The isoelectric points were found to be 6.4 +/- 0.1 for the specific 5'-nucleotidase and 6.8 +/- 0.1 for the phosphatase."}
{"id": "PMID:29022", "title": "Improved localization of thiamine pyrophosphatase activity in mounted cryostat sections using gel fixation and gel incubation media.", "content": "The presence of 1% agar in the fixation and substrate solutions for the histochemical demonstration of thiamine pyrophosphatase (4.4 mM TPP; 3.6 mM Pb2+; 0.025 Tris-maleate buffer, pH 7.2) clearly facilitates the localization of the enzyme in Golgi apparatus in cold microtome sections prepared from unfixed specimens.", "contents": "Improved localization of thiamine pyrophosphatase activity in mounted cryostat sections using gel fixation and gel incubation media. The presence of 1% agar in the fixation and substrate solutions for the histochemical demonstration of thiamine pyrophosphatase (4.4 mM TPP; 3.6 mM Pb2+; 0.025 Tris-maleate buffer, pH 7.2) clearly facilitates the localization of the enzyme in Golgi apparatus in cold microtome sections prepared from unfixed specimens."}
{"id": "PMID:29023", "title": "Differentiation of two types of endocrine cells which take up amine precursors using their capacity to take up the fluorescent dihydroisoquinoline derivative of dopamine.", "content": "A study was made of the accumulation of the strongly fluorescent 2-carboxymethyl-6,7-dihydroxy-3,4-dihydroisoquinolinium compound (2-Carb. Me-DIQ) derived from the condensation reaction of dopamine with glyoxylic acid in endocrine cells possessing the capacity to take up and store biogenic monoamine precursors. Thin-layer chromatographic studies of urine showed that 2-Carb. Me-DIQ was metabolized into two strongly fluorescent metabolites, possessing at least one hydroxyl group in the phenol moiety of the molecule, which were excreted in urine together with the parent compound. Histochemical observations, however, indicated that the tissue fluorescence showing maximal emission at 480 nm was due to 2-Carb. Me-DIQ. Generally, the injection of 2-Carb. Me-DIQ induced a strong fluorescence in those tissue components possessing the extraneuronal uptake mechanism of catecholamines. In the endocrine cells strong fluorescence was seen in the pineal glandular cells and in some cells of the pars distalis of the hypophysis, of which some cells also took up DL-5-HTP, as was seen following formaldehyde vapour treatment. No accumulation of 2-Carb. Me-DIQ was observed in the pancreatic islet cells, the C cells of the thyroid gland or the tracheal enterochromaffin-like cells. These findings lead to the conclusion that biogenic monoamines in the cells of the pars distalis of the hypophysis might use the phenolic moiety of the molecule to bind to some intracellular receptor. Thus, the pars distalis cells may have an intracellular binding mechanism for biogenic monoamines that is different from other endocrine cells showing the uptake and storage of biogenic monoamines. On the other hand, the findings gave further support to the suggestion that in the pancreatic islet cells, the thyroidal C cells and the tracheal enterochromaffin-like cells biogenic monoamines are stored by a mechanism in which the basic, positively charged amino group of biogenic monoamines is bound electrostatically to the anionic, negatively charged carboxyl group of a hormone storage granule. The pars distalis cells and the pineal glandular cells seemed to take up amines and amine derivatives in a similar manner. This suggests that in the pars distalis cells, too, biogenic monoamines have an active metabolism and possibly some regulative role in hormone synthesis and/or secretion.", "contents": "Differentiation of two types of endocrine cells which take up amine precursors using their capacity to take up the fluorescent dihydroisoquinoline derivative of dopamine. A study was made of the accumulation of the strongly fluorescent 2-carboxymethyl-6,7-dihydroxy-3,4-dihydroisoquinolinium compound (2-Carb. Me-DIQ) derived from the condensation reaction of dopamine with glyoxylic acid in endocrine cells possessing the capacity to take up and store biogenic monoamine precursors. Thin-layer chromatographic studies of urine showed that 2-Carb. Me-DIQ was metabolized into two strongly fluorescent metabolites, possessing at least one hydroxyl group in the phenol moiety of the molecule, which were excreted in urine together with the parent compound. Histochemical observations, however, indicated that the tissue fluorescence showing maximal emission at 480 nm was due to 2-Carb. Me-DIQ. Generally, the injection of 2-Carb. Me-DIQ induced a strong fluorescence in those tissue components possessing the extraneuronal uptake mechanism of catecholamines. In the endocrine cells strong fluorescence was seen in the pineal glandular cells and in some cells of the pars distalis of the hypophysis, of which some cells also took up DL-5-HTP, as was seen following formaldehyde vapour treatment. No accumulation of 2-Carb. Me-DIQ was observed in the pancreatic islet cells, the C cells of the thyroid gland or the tracheal enterochromaffin-like cells. These findings lead to the conclusion that biogenic monoamines in the cells of the pars distalis of the hypophysis might use the phenolic moiety of the molecule to bind to some intracellular receptor. Thus, the pars distalis cells may have an intracellular binding mechanism for biogenic monoamines that is different from other endocrine cells showing the uptake and storage of biogenic monoamines. On the other hand, the findings gave further support to the suggestion that in the pancreatic islet cells, the thyroidal C cells and the tracheal enterochromaffin-like cells biogenic monoamines are stored by a mechanism in which the basic, positively charged amino group of biogenic monoamines is bound electrostatically to the anionic, negatively charged carboxyl group of a hormone storage granule. The pars distalis cells and the pineal glandular cells seemed to take up amines and amine derivatives in a similar manner. This suggests that in the pars distalis cells, too, biogenic monoamines have an active metabolism and possibly some regulative role in hormone synthesis and/or secretion."}
{"id": "PMID:29024", "title": "Determination of the metabolites of bezitramide in urine. II. The basic metabolite.", "content": "A high-performance liquid chromatographic method for the determination of low levels (less than 1 microgram/ml) of the basic metabolite of bezitramide, 1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one, in human urine is described. Special attention is given to the separation from the basic metabolite of droperidol, a drug frequently co-administered with bezitramide.", "contents": "Determination of the metabolites of bezitramide in urine. II. The basic metabolite. A high-performance liquid chromatographic method for the determination of low levels (less than 1 microgram/ml) of the basic metabolite of bezitramide, 1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one, in human urine is described. Special attention is given to the separation from the basic metabolite of droperidol, a drug frequently co-administered with bezitramide."}
{"id": "PMID:29030", "title": "Prevalence of self-injurious behaviors in a large state facility for the retarded: a three-year follow-up study.", "content": "A combined informant questionnaire and interview survey of self-injurious behavior (SIB) at a large state facility for the retarded was conducted independently three times over a 3-year period. Prevalence consistently was about 10% of the population. SIB cases tended to be younger and institutionalized longer than the rest of the population. Severe cases had a longer history of chronic SIB. SIB cases had more seizure disorders, severe language handicaps, visual impairments, and severe or profound retardation than the rest of the population. They appeared to fulfill most of the Rutter (1966) criteria for autism. But unlike the severely autistic, there was little relation of sex to incidence of SIB. Over 90% of SIB cases changed status over 3 years, suggesting that SIB was amenable to behavior modification in most cases (94%). Psychotropic behavior control medications helped in some intervention programs (32%). SIB remitted spontaneously in 21% of SIB cases where there had been no behavioral or drug intervention.", "contents": "Prevalence of self-injurious behaviors in a large state facility for the retarded: a three-year follow-up study. A combined informant questionnaire and interview survey of self-injurious behavior (SIB) at a large state facility for the retarded was conducted independently three times over a 3-year period. Prevalence consistently was about 10% of the population. SIB cases tended to be younger and institutionalized longer than the rest of the population. Severe cases had a longer history of chronic SIB. SIB cases had more seizure disorders, severe language handicaps, visual impairments, and severe or profound retardation than the rest of the population. They appeared to fulfill most of the Rutter (1966) criteria for autism. But unlike the severely autistic, there was little relation of sex to incidence of SIB. Over 90% of SIB cases changed status over 3 years, suggesting that SIB was amenable to behavior modification in most cases (94%). Psychotropic behavior control medications helped in some intervention programs (32%). SIB remitted spontaneously in 21% of SIB cases where there had been no behavioral or drug intervention."}
{"id": "PMID:29031", "title": "Autolysins and shape change in rodA mutants of Bacillus subtilis.", "content": "The biochemical phenotype of rodA mutants was not affected by the simultaneous presence in double mutants of the lyt gene which makes them 90 to 95% deficient in autolysin action. The only morphological effect of this deficiency on the expression of the rod gene was that both the rod and the coccal forms of the mutant failed to separate and grew as long chains of cells. Inhibition of protein synthesis stopped the increase in peptidoglycan that occurred when the growth temperature for the mutants was raised to 45 degrees C. These observations support the idea that a derepression of peptidoglycan synthesis occurs at this temperature. The increased amount of cellular peptidoglycan at the higher growth temperature is not likely to be the result of the concomitant switching off of autolytic enzyme action.", "contents": "Autolysins and shape change in rodA mutants of Bacillus subtilis. The biochemical phenotype of rodA mutants was not affected by the simultaneous presence in double mutants of the lyt gene which makes them 90 to 95% deficient in autolysin action. The only morphological effect of this deficiency on the expression of the rod gene was that both the rod and the coccal forms of the mutant failed to separate and grew as long chains of cells. Inhibition of protein synthesis stopped the increase in peptidoglycan that occurred when the growth temperature for the mutants was raised to 45 degrees C. These observations support the idea that a derepression of peptidoglycan synthesis occurs at this temperature. The increased amount of cellular peptidoglycan at the higher growth temperature is not likely to be the result of the concomitant switching off of autolytic enzyme action."}
{"id": "PMID:29032", "title": "ATP activation and properties of the methyl coenzyme M reductase system in Methanobacterium thermoautotrophicum.", "content": "The requirement of ATP for the methyl coenzyme M methylreductase in extracts of Methanobacterium thermoautotrophicum was found to be catalytic; for each mol of ATP added, 15 mol of methane was produced from methyl coenzyme M [2-(methylthio)ethanesulfonic acid]. Other nucleotide triphosphates partially replaced ATP in activation of the reductase. All components of the reaction were found in the supernatant fraction of cell extracts after centrifugation at 100,000 X g for 1 h; optimal reaction rates occurred at 65 degrees C, at a pH range of 5.6 to 6.0, and at concentrations of ATP and MgCl2 of 1 mM and 40 mM, respectively. Chloral hydrate, chloroform, nitrite, 2,4-dinitrophenol, and viologen dyes (compounds known to inhibit methanogenesis from a variety of substrates) were found to inhibit the conversion of methyl coenzyme M to methane. Methyl coenzyme M methylreductase was shown to be present in a variety of methanogens.", "contents": "ATP activation and properties of the methyl coenzyme M reductase system in Methanobacterium thermoautotrophicum. The requirement of ATP for the methyl coenzyme M methylreductase in extracts of Methanobacterium thermoautotrophicum was found to be catalytic; for each mol of ATP added, 15 mol of methane was produced from methyl coenzyme M [2-(methylthio)ethanesulfonic acid]. Other nucleotide triphosphates partially replaced ATP in activation of the reductase. All components of the reaction were found in the supernatant fraction of cell extracts after centrifugation at 100,000 X g for 1 h; optimal reaction rates occurred at 65 degrees C, at a pH range of 5.6 to 6.0, and at concentrations of ATP and MgCl2 of 1 mM and 40 mM, respectively. Chloral hydrate, chloroform, nitrite, 2,4-dinitrophenol, and viologen dyes (compounds known to inhibit methanogenesis from a variety of substrates) were found to inhibit the conversion of methyl coenzyme M to methane. Methyl coenzyme M methylreductase was shown to be present in a variety of methanogens."}
{"id": "PMID:29033", "title": "Psychoactive drug interactions.", "content": "Interactions can arise from serial or simultaneous administration of 2 or more drugs. Interactions with other medications can enhance or diminish either the clinical usefulness of a drug, or its toxic effects. Interactions can arise from changes in absorption, protein binding, metabolism, excretion or activity at a common site of action. Drug interactions of clinical interest to psychiatrists are described. The drugs include: stimulants, neuroleptics, tricyclic antidepressants, monoamine oxidase inhibitors, lithium, anticonvulsants, and sedatives and hypnotics.", "contents": "Psychoactive drug interactions. Interactions can arise from serial or simultaneous administration of 2 or more drugs. Interactions with other medications can enhance or diminish either the clinical usefulness of a drug, or its toxic effects. Interactions can arise from changes in absorption, protein binding, metabolism, excretion or activity at a common site of action. Drug interactions of clinical interest to psychiatrists are described. The drugs include: stimulants, neuroleptics, tricyclic antidepressants, monoamine oxidase inhibitors, lithium, anticonvulsants, and sedatives and hypnotics."}
{"id": "PMID:29034", "title": "Phosphorus nuclear magnetic resonance studies of phosphorus metabolites in frog muscle.", "content": "31P-nuclear magnetic resonance was applied to living muscles of bullfrogs, and the time courses of metabolic changes of ATP, creatine phosphate, inorganic phosphate, and sugar phosphates were studied under anaerobic and aerobic conditions. A decrease in creatine phosphate was observed in the resting muscle under anaerobic conditions with a concomitant decrease in the intracellular pH, while the ATP level remained constant. With the use of 2,4-dinitro-1-fluorobenzene and iodoacetic acid, ATP disappeared quickly. When the resting muscle was perfused with oxygen-saturated glucose-Ringer's solution, the amount of creatine phosphate increased gradually. These findings indicate that anaerobic glycolysis is insufficient for even the resting energy consumption whereas oxidative phosphorylation is sufficient. The effects of tetanic stimulation on living muscles were also studied. When glycolysis and oxidative phosphorylation were suppressed, the intracellular energy store was depleted by the tetanic contraction. Anaerobic glycolysis produced rapid recovery of the energy store level, although it was insufficient to reach the initial level. Aerobic oxidative phosphorylation produced sufficient energy to reach the initial level, and this level was never exceeded. This finding suggests the existence of a regulatory mechanism for the energy store level.", "contents": "Phosphorus nuclear magnetic resonance studies of phosphorus metabolites in frog muscle. 31P-nuclear magnetic resonance was applied to living muscles of bullfrogs, and the time courses of metabolic changes of ATP, creatine phosphate, inorganic phosphate, and sugar phosphates were studied under anaerobic and aerobic conditions. A decrease in creatine phosphate was observed in the resting muscle under anaerobic conditions with a concomitant decrease in the intracellular pH, while the ATP level remained constant. With the use of 2,4-dinitro-1-fluorobenzene and iodoacetic acid, ATP disappeared quickly. When the resting muscle was perfused with oxygen-saturated glucose-Ringer's solution, the amount of creatine phosphate increased gradually. These findings indicate that anaerobic glycolysis is insufficient for even the resting energy consumption whereas oxidative phosphorylation is sufficient. The effects of tetanic stimulation on living muscles were also studied. When glycolysis and oxidative phosphorylation were suppressed, the intracellular energy store was depleted by the tetanic contraction. Anaerobic glycolysis produced rapid recovery of the energy store level, although it was insufficient to reach the initial level. Aerobic oxidative phosphorylation produced sufficient energy to reach the initial level, and this level was never exceeded. This finding suggests the existence of a regulatory mechanism for the energy store level."}
{"id": "PMID:29036", "title": "Purification and some properties of a specific nuclease which cleaves transfer RNA precursors from the posterior silk gland of Bombyx mori.", "content": "A specific endonuclease involved in the processing of tRNA precursors was isolated and partially purified from the posterior silk gland of Bombyx mori, and designated as RNase P.Bmo. This enzyme was shown to catalyze the conversion of 4.5 S precursor RNA to 4.1 S RNA by trimming the 5'-additional segment from the precursor RNA. RNase P.Bmo required divalent cations, Mg2+ or Mn2+. In the presence of these divalent cations, K+ or NH4+ activated the RNase P.Bmo reaction. Optimum pH was observed around 8.0. Ribosomal RNA's and mature tRNA from the silk gland were not cleaved by RNase P.Bmo. A 4.5 S precursor RNA fraction containing formycin, an adenosine analog, was less susceptible to RNase P.Bmo than the normal one. These results indicate that RNase P.Bmo has a high substrate specificity. An additional nuclease(s) was isolated. This activity was assumed to remove the extra 3'-segment of the 4.5 S precursor RNA.", "contents": "Purification and some properties of a specific nuclease which cleaves transfer RNA precursors from the posterior silk gland of Bombyx mori. A specific endonuclease involved in the processing of tRNA precursors was isolated and partially purified from the posterior silk gland of Bombyx mori, and designated as RNase P.Bmo. This enzyme was shown to catalyze the conversion of 4.5 S precursor RNA to 4.1 S RNA by trimming the 5'-additional segment from the precursor RNA. RNase P.Bmo required divalent cations, Mg2+ or Mn2+. In the presence of these divalent cations, K+ or NH4+ activated the RNase P.Bmo reaction. Optimum pH was observed around 8.0. Ribosomal RNA's and mature tRNA from the silk gland were not cleaved by RNase P.Bmo. A 4.5 S precursor RNA fraction containing formycin, an adenosine analog, was less susceptible to RNase P.Bmo than the normal one. These results indicate that RNase P.Bmo has a high substrate specificity. An additional nuclease(s) was isolated. This activity was assumed to remove the extra 3'-segment of the 4.5 S precursor RNA."}
{"id": "PMID:29037", "title": "Purification and properties of acetate kinase from Bacillus stearothermophilus.", "content": "1. Acetate kinase [EC 2.7.2.1] from an thermophile, B. stearothermophilus, was purified and crystalized. 2. This enzyme was shown to be a tetramer of identical subunits which had a molecular weight of about 40,000. Amino acid analysis showed no SH group. By analyzing the CD spectrum it was deduced that this enzyme is composed of 36% beta-structure, 21% alpha-helix and 43% unordered structure. 3. This enzyme shared many common enzymatic properties with the counterpart from mesophiles, i.e. pH optimum, substrate specificity, requirement of metal ions and essential amino acid residues necessary for the catalytic activity. However, this enzyme was remarkably thermostable. 4. A plot of the reaction velocity against the concentration of acetate, ADP or acetyl phosphate gave a curve of the Michaelis-Menten type. However, such a plot against ATP gave a sigmoid curve, suggesting a homotropic allosteric nature of the enzyme. 5. From the results of chemical modification it was deduced that an amino group and an imidazole group, at least, are involved in the active site of the enzyme.", "contents": "Purification and properties of acetate kinase from Bacillus stearothermophilus. 1. Acetate kinase [EC 2.7.2.1] from an thermophile, B. stearothermophilus, was purified and crystalized. 2. This enzyme was shown to be a tetramer of identical subunits which had a molecular weight of about 40,000. Amino acid analysis showed no SH group. By analyzing the CD spectrum it was deduced that this enzyme is composed of 36% beta-structure, 21% alpha-helix and 43% unordered structure. 3. This enzyme shared many common enzymatic properties with the counterpart from mesophiles, i.e. pH optimum, substrate specificity, requirement of metal ions and essential amino acid residues necessary for the catalytic activity. However, this enzyme was remarkably thermostable. 4. A plot of the reaction velocity against the concentration of acetate, ADP or acetyl phosphate gave a curve of the Michaelis-Menten type. However, such a plot against ATP gave a sigmoid curve, suggesting a homotropic allosteric nature of the enzyme. 5. From the results of chemical modification it was deduced that an amino group and an imidazole group, at least, are involved in the active site of the enzyme."}
{"id": "PMID:29038", "title": "Studies of a calcium-activated neutral protease from chicken skeletal muscle. I. Purification and characterization.", "content": "A calcium-activated neutral protease was purified 2,700-fold over the crude extract from chicken skeletal muscle. The purified protease migrated as a single band on polyacrylamide gel electrophoresis with or without SDS. Its molecular weight was 80,000 and pH optimum for activity was 7.7. The activity required strictly the presence of calcium (optimum concentration: 1.8 mM) or strontium (optimum concentration: 10 mM) ions. The protease was inhibited by leupeptin, which is known to be a strong inhibitor of papain, cathepsin B, trypsin, and plasmin.", "contents": "Studies of a calcium-activated neutral protease from chicken skeletal muscle. I. Purification and characterization. A calcium-activated neutral protease was purified 2,700-fold over the crude extract from chicken skeletal muscle. The purified protease migrated as a single band on polyacrylamide gel electrophoresis with or without SDS. Its molecular weight was 80,000 and pH optimum for activity was 7.7. The activity required strictly the presence of calcium (optimum concentration: 1.8 mM) or strontium (optimum concentration: 10 mM) ions. The protease was inhibited by leupeptin, which is known to be a strong inhibitor of papain, cathepsin B, trypsin, and plasmin."}
{"id": "PMID:29039", "title": "Studies on cellulases of a phytopathogenic fungus, Pyricularia oryzae cavara. II. Purification and properties of a beta-glucosidase.", "content": "Three components (GA, GB-1, and GB-2) of beta-glucosidase were detected in the culture filtrate of Pyricularia oryzae grown in a cellulose or cellulose derivative medium. Among them, GB-1 was induced most strongly. Purified GB-1 was homogeneous on polyacrylamide gel electrophoresis and showed an approximately 1,400-fold increase of specific activity over the starting material. The molecular weight was determined to be 240,000 by sodium dodecyl sulfate-gel electrophoresis. A similar value was also obtained by sucrose density gradient centrifugation. The enzyme contained a high proportion of acidic amino acids and mannose, and the isoelectric point of the enzyme was pH 4.15. The enzyme had a pH optimum of 5.5 and a temperature optimum at 55 degrees C. beta-Glucosidase activity was inhibited by Mn2+, Cu2+, Hg2+, p-chloromercuribenzoate, and glucono-delta-lactone. The enzyme split off glucose units one by one from the nonreducing ends of not only beta-glucooligosaccharides but also some beta-glucans, such as carboxymethylcellulose, laminaran, pustulan, and zeagallan. The affinity for cello- and laminari-oligosaccharides tended to increase in parallel with the chain length.", "contents": "Studies on cellulases of a phytopathogenic fungus, Pyricularia oryzae cavara. II. Purification and properties of a beta-glucosidase. Three components (GA, GB-1, and GB-2) of beta-glucosidase were detected in the culture filtrate of Pyricularia oryzae grown in a cellulose or cellulose derivative medium. Among them, GB-1 was induced most strongly. Purified GB-1 was homogeneous on polyacrylamide gel electrophoresis and showed an approximately 1,400-fold increase of specific activity over the starting material. The molecular weight was determined to be 240,000 by sodium dodecyl sulfate-gel electrophoresis. A similar value was also obtained by sucrose density gradient centrifugation. The enzyme contained a high proportion of acidic amino acids and mannose, and the isoelectric point of the enzyme was pH 4.15. The enzyme had a pH optimum of 5.5 and a temperature optimum at 55 degrees C. beta-Glucosidase activity was inhibited by Mn2+, Cu2+, Hg2+, p-chloromercuribenzoate, and glucono-delta-lactone. The enzyme split off glucose units one by one from the nonreducing ends of not only beta-glucooligosaccharides but also some beta-glucans, such as carboxymethylcellulose, laminaran, pustulan, and zeagallan. The affinity for cello- and laminari-oligosaccharides tended to increase in parallel with the chain length."}
{"id": "PMID:29040", "title": "Pyridine nucleotide interaction with rat liver dihydropteridine reductase.", "content": "The interactions of a homogeneous preparation of rat liver dihydropteridine reductase with NADH, NADPH, NAD+, NADP+, and the 1-N6-ethenoadenine derivative of NAD+ have been investigated by fluorescence titration, circular dichroism, equilibrium dialysis, Sephadex G-25 chromatography, and polyacrylamide gel electrophoresis. The procedures indicate that the dimeric enzyme has a definite preference for NADH, but binds only 1 mol of this nucleotide per mol of enzyme. The binary complex of enzyme with NADH is only partially stable to exhaustive dialysis and gel electrophoresis, where it shows greater mobility (0.26) than the free enzyme (0.21); however, the complex can be isolated by Sephadex G-25 chromatography, and characterized with respect to its absorbance spectrum. No ternary complexes are observed when samples of reductase, preincubated with excess NADH, and either the reaction product, 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, or the inhibitor, methotrexate, are subjected to polyacrylamide gel electrophoresis.", "contents": "Pyridine nucleotide interaction with rat liver dihydropteridine reductase. The interactions of a homogeneous preparation of rat liver dihydropteridine reductase with NADH, NADPH, NAD+, NADP+, and the 1-N6-ethenoadenine derivative of NAD+ have been investigated by fluorescence titration, circular dichroism, equilibrium dialysis, Sephadex G-25 chromatography, and polyacrylamide gel electrophoresis. The procedures indicate that the dimeric enzyme has a definite preference for NADH, but binds only 1 mol of this nucleotide per mol of enzyme. The binary complex of enzyme with NADH is only partially stable to exhaustive dialysis and gel electrophoresis, where it shows greater mobility (0.26) than the free enzyme (0.21); however, the complex can be isolated by Sephadex G-25 chromatography, and characterized with respect to its absorbance spectrum. No ternary complexes are observed when samples of reductase, preincubated with excess NADH, and either the reaction product, 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, or the inhibitor, methotrexate, are subjected to polyacrylamide gel electrophoresis."}
{"id": "PMID:29041", "title": "Membrane bioenergetic parameters in uncoupler-resistant mutants of Bacillus megaterium.", "content": "Mutants of Bacillus megaterium displaying malate-driven ATP synthesis resistant to uncouplers of oxidative posphorylation are further characterized. Both the pH gradient and electrical potential generated across the membrane by malate respiration are equally sensitive to uncouplers in the wild type and uncoupler-resistant mutants. The mutants possess 0 to 10% of the wild type ATPase activity which is not activated by pretreatment with heat or trypsin. Despite this inability to measure ATPase activity, the mutants demonstrate acid-pulse-driven ATPase synthesis which is sensitive to uncouplers as well as malate-driven ATP synthesis which becomes uncoupler sensitive at pH 5.5. N,N' -Dicyclohexylcarbodiimide and valinomycin plus potassium inhibition of ATP synthesis is reversed by uncouplers in the mutants but not in the wild type. The data support the existence of a specific site on the ATPase complex for uncoupler binding which, if altered by mutation, affects uncoupler binding to the complex. The retention of malate-driven ATP synthesis in the absence of a significant pH gradient or electrical potential suggests that an alternative intermediate is involved in coupling oxidation to phosphorylation.", "contents": "Membrane bioenergetic parameters in uncoupler-resistant mutants of Bacillus megaterium. Mutants of Bacillus megaterium displaying malate-driven ATP synthesis resistant to uncouplers of oxidative posphorylation are further characterized. Both the pH gradient and electrical potential generated across the membrane by malate respiration are equally sensitive to uncouplers in the wild type and uncoupler-resistant mutants. The mutants possess 0 to 10% of the wild type ATPase activity which is not activated by pretreatment with heat or trypsin. Despite this inability to measure ATPase activity, the mutants demonstrate acid-pulse-driven ATPase synthesis which is sensitive to uncouplers as well as malate-driven ATP synthesis which becomes uncoupler sensitive at pH 5.5. N,N' -Dicyclohexylcarbodiimide and valinomycin plus potassium inhibition of ATP synthesis is reversed by uncouplers in the mutants but not in the wild type. The data support the existence of a specific site on the ATPase complex for uncoupler binding which, if altered by mutation, affects uncoupler binding to the complex. The retention of malate-driven ATP synthesis in the absence of a significant pH gradient or electrical potential suggests that an alternative intermediate is involved in coupling oxidation to phosphorylation."}
{"id": "PMID:29042", "title": "Subunit interactions of Glycera dibranchiata hemoglobin.", "content": "The coelomic cells of the polychaete annelid Glycera dibranchiata contain two hemoglobins. The monomer hemoglobin fraction is composed of one major component and two minor components as determined by starch gel electrophoresis and isoelectrofocusing, but is homogeneous as to subunit size as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The polymer hemoglobin fraction has and initial molecular weight of Mn = 125,000 as determined by osmometry, but exhibits an increased state of aggregation upon storage. The quaternary structure of the polymer is constituted of monomeric subunits in a non-covalent state of aggregation as demonstrated by its subunit dissociation inthe presence of propyl urea. The oxygen affinity of the polymer is lower than the monomer but increases with deaggregation. The Bohr effect is present only in the polymer. Cooperativity is also characteristic of the polymer and is pH-dependent. Interestingly, cooperativity increases with intermediate states of polymer deaggregation. By far, the main organic phosphate component of the coelomic red cells is ATP accompanied by small amounts of ADP and GTP. No modulating effect of ATP on the oxygen equilibrium of either polymer or total hemolysate was found.", "contents": "Subunit interactions of Glycera dibranchiata hemoglobin. The coelomic cells of the polychaete annelid Glycera dibranchiata contain two hemoglobins. The monomer hemoglobin fraction is composed of one major component and two minor components as determined by starch gel electrophoresis and isoelectrofocusing, but is homogeneous as to subunit size as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The polymer hemoglobin fraction has and initial molecular weight of Mn = 125,000 as determined by osmometry, but exhibits an increased state of aggregation upon storage. The quaternary structure of the polymer is constituted of monomeric subunits in a non-covalent state of aggregation as demonstrated by its subunit dissociation inthe presence of propyl urea. The oxygen affinity of the polymer is lower than the monomer but increases with deaggregation. The Bohr effect is present only in the polymer. Cooperativity is also characteristic of the polymer and is pH-dependent. Interestingly, cooperativity increases with intermediate states of polymer deaggregation. By far, the main organic phosphate component of the coelomic red cells is ATP accompanied by small amounts of ADP and GTP. No modulating effect of ATP on the oxygen equilibrium of either polymer or total hemolysate was found."}
{"id": "PMID:29046", "title": "A spectral probe near the subunit catalytic site of glutamine synthetase from Escherichia coli. Reduced pyridoxal 5'-phosphate.enzyme complexes.", "content": "In order to label phosphate binding sites, unadenylylated glutamine synthetase from Escherichia coli has been pyridoxylated by reacting the enzyme with pyridoxal 5'-phosphate followed by reduction of the Schiff base with NaBH4. A complete loss in Mg2+-supported activity is associated with the incorporation of 3 eq of pyridoxal-P/subunit of the dodecamer. At this extent of modification, however, the pyridoxylated enzyme exhibits substantial Mn2+-supported activity (with increased Km values for ATP and ADP). The sites of pyridoxylation appear to have equal affinities for pyridoxal-P and to be at the enzyme surface, freely accessible to solvent. At least one of the three covalently bound pyridoxamine 5'-phosphate groups is near the subunit catalytic site and acts as a spectral probe for the interactions of the manganese.enzyme with substrates. A spectral perturbation of covalently attached pyridoxamine-P groups is caused also by specific divalent cations (Mn2+, Mg2+ or Ca2+) binding at the subunit catalytic site (but not while binding to the subunit high affinity, activating Me2+ site). In addition, the feedback inhibitors, AMP, CTP, L-tryptophan, L-alanine, and carbamyl phosphate, perturb protein-bound pyridoxamine-P groups. The spectral perturbations produced by substrate and inhibitor binding are pH-dependent and different in magnitude and maximum wavelength. Adenylylation sites are not major sites of pyridoxylation.", "contents": "A spectral probe near the subunit catalytic site of glutamine synthetase from Escherichia coli. Reduced pyridoxal 5'-phosphate.enzyme complexes. In order to label phosphate binding sites, unadenylylated glutamine synthetase from Escherichia coli has been pyridoxylated by reacting the enzyme with pyridoxal 5'-phosphate followed by reduction of the Schiff base with NaBH4. A complete loss in Mg2+-supported activity is associated with the incorporation of 3 eq of pyridoxal-P/subunit of the dodecamer. At this extent of modification, however, the pyridoxylated enzyme exhibits substantial Mn2+-supported activity (with increased Km values for ATP and ADP). The sites of pyridoxylation appear to have equal affinities for pyridoxal-P and to be at the enzyme surface, freely accessible to solvent. At least one of the three covalently bound pyridoxamine 5'-phosphate groups is near the subunit catalytic site and acts as a spectral probe for the interactions of the manganese.enzyme with substrates. A spectral perturbation of covalently attached pyridoxamine-P groups is caused also by specific divalent cations (Mn2+, Mg2+ or Ca2+) binding at the subunit catalytic site (but not while binding to the subunit high affinity, activating Me2+ site). In addition, the feedback inhibitors, AMP, CTP, L-tryptophan, L-alanine, and carbamyl phosphate, perturb protein-bound pyridoxamine-P groups. The spectral perturbations produced by substrate and inhibitor binding are pH-dependent and different in magnitude and maximum wavelength. Adenylylation sites are not major sites of pyridoxylation."}
{"id": "PMID:29047", "title": "The internal pH of isolated serotonin containing granules of pig platelets.", "content": "The [14C]methylamine distribution method was utilized to measure the internal pH of isolated serotonin containing granules of pig blood platelets under varying conditions. The granules used were isolated by a new protocol which stressed platelet rupture under controlled conditions and preservation of isotonicity throughout the isolation procedure, In a well buffered external medium, pH 6.85, The deltapH was measured as 1.11 with the internal pH being found acidic (pH 5.74). Increasing the external pH produced a corresponding increase in the deltaH. The pH gradient could be collapsed by the addition of ionophores and uncouplers which are known to transport protons across biological membranes. In addition, the deltapH was constant for granules suspended in various ionic media, thus suggesting that the deltaH did not arise secondarily due to the establishment of a Donnan equilibrium. The existence of the acidic intragranular space is discussed with respect to previous ancillary findings. Also, an explication of the possible physiological significance of the deltaH is presented.", "contents": "The internal pH of isolated serotonin containing granules of pig platelets. The [14C]methylamine distribution method was utilized to measure the internal pH of isolated serotonin containing granules of pig blood platelets under varying conditions. The granules used were isolated by a new protocol which stressed platelet rupture under controlled conditions and preservation of isotonicity throughout the isolation procedure, In a well buffered external medium, pH 6.85, The deltapH was measured as 1.11 with the internal pH being found acidic (pH 5.74). Increasing the external pH produced a corresponding increase in the deltaH. The pH gradient could be collapsed by the addition of ionophores and uncouplers which are known to transport protons across biological membranes. In addition, the deltapH was constant for granules suspended in various ionic media, thus suggesting that the deltaH did not arise secondarily due to the establishment of a Donnan equilibrium. The existence of the acidic intragranular space is discussed with respect to previous ancillary findings. Also, an explication of the possible physiological significance of the deltaH is presented."}
{"id": "PMID:29050", "title": "Nonrandom distribution of sialic acid over the cell surface of bristle-coated endocytic vesicles of the sinusoidal endothelium cells.", "content": "Previous studies with protein tracers have shown that the luminal surface of the vascular endothelium of the bone marrow is endocytic. The endocytosis occurs through the formation of large bristle-coated vesicles (LCV). The anionic charge distribution in this process was examined at the luminal surface of the endothelial cell, At pH 1.8, colloidal iron (CI), native ferritin, and polycationic ferritin (PCF) are bound by the luminal surface of the endothelial cell, but not at the sites of LCV formation. PCF used over a pH range of 1.8--7.2 (CI is unstable at higher pH levels) revealed LCV binding of this agent in increasing manner from pH 3.5 upwards. PCF binding at low pH (1.8) at the endothelial cell surface was markedly reduced by neuraminidase. Neuraminidase did not reduce PCF binding by the endothelial cell surface nor by the LCV at higher pH levels. It is concluded that the luminal surface of the endothelial cell has exposed sialic acid groups which are absent or significantly diminished at endocytic sites. The free surface of the endothelial cells as well as the sites of endocytosis have, in addition, anionic material with a pKa higher than that of sialic acid (pKa 2.6). These anionic materials may be different at the sites of endocytosis as compared to those present at the free cell surface.", "contents": "Nonrandom distribution of sialic acid over the cell surface of bristle-coated endocytic vesicles of the sinusoidal endothelium cells. Previous studies with protein tracers have shown that the luminal surface of the vascular endothelium of the bone marrow is endocytic. The endocytosis occurs through the formation of large bristle-coated vesicles (LCV). The anionic charge distribution in this process was examined at the luminal surface of the endothelial cell, At pH 1.8, colloidal iron (CI), native ferritin, and polycationic ferritin (PCF) are bound by the luminal surface of the endothelial cell, but not at the sites of LCV formation. PCF used over a pH range of 1.8--7.2 (CI is unstable at higher pH levels) revealed LCV binding of this agent in increasing manner from pH 3.5 upwards. PCF binding at low pH (1.8) at the endothelial cell surface was markedly reduced by neuraminidase. Neuraminidase did not reduce PCF binding by the endothelial cell surface nor by the LCV at higher pH levels. It is concluded that the luminal surface of the endothelial cell has exposed sialic acid groups which are absent or significantly diminished at endocytic sites. The free surface of the endothelial cells as well as the sites of endocytosis have, in addition, anionic material with a pKa higher than that of sialic acid (pKa 2.6). These anionic materials may be different at the sites of endocytosis as compared to those present at the free cell surface."}
{"id": "PMID:29051", "title": "Hemagglutination with simian papovavirus SA12.", "content": "Simian papovavirus SA12 agglutinated human, guinea pig, and chicken erythrocytes. SA12 hemagglutinin was most effectively released from debris of infected tissue culture cells at an alkaline pH.", "contents": "Hemagglutination with simian papovavirus SA12. Simian papovavirus SA12 agglutinated human, guinea pig, and chicken erythrocytes. SA12 hemagglutinin was most effectively released from debris of infected tissue culture cells at an alkaline pH."}
{"id": "PMID:29052", "title": "Relationship between the rate of H+ transport and pathways of glucose metabolism by turtle urinary bladder.", "content": "The urinary bladder of the fresh-water turtle acidifies its contents by actively transporting H(+) ions across the luminal membrane. It is known that the H(+) transport system is dependent upon oxidative metabolism and the substrate glucose; however, the specific biochemical events resulting in H(+) translocation have not been identified. This study examines the relationship between active H(+) transport and a specific oxidative pathway of glucose metabolism, the pentose phosphate shunt. To investigate this relationship the metabolic and transport rates were simultaneously measured under several well-defined conditions. When H(+) transport was inhibited by either the application of an opposing pH gradient or by acetazolamide, glucose metabolism by the pentose phosphate shunt declined. Conversely, stimulation of H(+) transport by either imposing a more favorable pH gradient or by CO(2) addition resulted in an increase in pentose phosphate shunt metabolism. Glycolytic activity, in contrast, was invariant with the maneuvers which altered the rate of H(+) transport. Additional experiments localized pentose phosphate shunt enzyme activity to the mucosal fraction of the bladder which is the cell layer responsible for acid secretion. The finding that the rate of glucose metabolism by the pentose phosphate shunt is related to the rate of H(+) transport suggests but does not prove that the pentose phosphate shunt may be an important metabolic pathway for H(+) transport by the turtle urinary bladder.", "contents": "Relationship between the rate of H+ transport and pathways of glucose metabolism by turtle urinary bladder. The urinary bladder of the fresh-water turtle acidifies its contents by actively transporting H(+) ions across the luminal membrane. It is known that the H(+) transport system is dependent upon oxidative metabolism and the substrate glucose; however, the specific biochemical events resulting in H(+) translocation have not been identified. This study examines the relationship between active H(+) transport and a specific oxidative pathway of glucose metabolism, the pentose phosphate shunt. To investigate this relationship the metabolic and transport rates were simultaneously measured under several well-defined conditions. When H(+) transport was inhibited by either the application of an opposing pH gradient or by acetazolamide, glucose metabolism by the pentose phosphate shunt declined. Conversely, stimulation of H(+) transport by either imposing a more favorable pH gradient or by CO(2) addition resulted in an increase in pentose phosphate shunt metabolism. Glycolytic activity, in contrast, was invariant with the maneuvers which altered the rate of H(+) transport. Additional experiments localized pentose phosphate shunt enzyme activity to the mucosal fraction of the bladder which is the cell layer responsible for acid secretion. The finding that the rate of glucose metabolism by the pentose phosphate shunt is related to the rate of H(+) transport suggests but does not prove that the pentose phosphate shunt may be an important metabolic pathway for H(+) transport by the turtle urinary bladder."}
{"id": "PMID:29053", "title": "Tissue guanosine-3',5'-cyclic monophosphate levels and soluble guanylate cyclase activity: a positive correlation during unilateral cryptorchidism in the rat testis.", "content": "The relationship between the subcellular distribution of guanylate cyclase and tissue guanosine-3',5'-cyclic monophosphate (cGMP) levels was investigated in rat testes after surgically induced unilateral cryptorchidism. Placement of one of a testis pair in the abdominal cavity results in loss of testicular weight and function in the abdominal testis whereas the remaining scrotal testis appears to be functionally normal. Within 5 days after surgery, tissue cGMP levels were increased by twofold in the abdominal testis. A fourfold elevation was noted from 10 to 30 days after surgery. Whereas the homogenate guanylate cyclase activity was only slightly elevated 10 and 20 days postoperatively, a 200% increase in the soluble guanylate cyclase activity was seen at 5 days. Between 10 and 30 days, the rise in activity was >250% (P < 0.01). An increase in soluble guanylate cyclase activity was noted when the data were expressed as per milligram protein, per milligram DNA or per whole testis. Conversely, particulate guanylate cyclase activity was reduced by 40% in the cryptorchid testis. Kinetic analysis of the soluble enzyme prepared from abdominal and scrotal testes yielded linear Line-weaver-Burke plots for both enzyme preparations with an identical K(m) for guanosine triphosphate, but a three-fold higher maximal velocity for the abdominal enzyme. When the soluble guanylate cyclases from both testes were mixed and assayed together, the activities were additive rather than exhibiting synergism or inhibition. These experiments indicate that the altered V(max) is not due to a transferable activator or inhibitor.An immunocytochemical technique was used to assess the cell type in which the alterations in cGMP metabolism occurred. Comparison of the scrotal and abdominal testes revealed that the abdominal testis exhibited enhanced cGMP immunofluorescence within the cells lining the inner aspect of the seminiferous tubule as well as tubular elements and interstitial cells. Thus, it is inferred that the correlated changes in soluble guanylate cyclase activity and cGMP levels occur in several of the cell types that remain viable within the cryptorchid testis.", "contents": "Tissue guanosine-3',5'-cyclic monophosphate levels and soluble guanylate cyclase activity: a positive correlation during unilateral cryptorchidism in the rat testis. The relationship between the subcellular distribution of guanylate cyclase and tissue guanosine-3',5'-cyclic monophosphate (cGMP) levels was investigated in rat testes after surgically induced unilateral cryptorchidism. Placement of one of a testis pair in the abdominal cavity results in loss of testicular weight and function in the abdominal testis whereas the remaining scrotal testis appears to be functionally normal. Within 5 days after surgery, tissue cGMP levels were increased by twofold in the abdominal testis. A fourfold elevation was noted from 10 to 30 days after surgery. Whereas the homogenate guanylate cyclase activity was only slightly elevated 10 and 20 days postoperatively, a 200% increase in the soluble guanylate cyclase activity was seen at 5 days. Between 10 and 30 days, the rise in activity was >250% (P < 0.01). An increase in soluble guanylate cyclase activity was noted when the data were expressed as per milligram protein, per milligram DNA or per whole testis. Conversely, particulate guanylate cyclase activity was reduced by 40% in the cryptorchid testis. Kinetic analysis of the soluble enzyme prepared from abdominal and scrotal testes yielded linear Line-weaver-Burke plots for both enzyme preparations with an identical K(m) for guanosine triphosphate, but a three-fold higher maximal velocity for the abdominal enzyme. When the soluble guanylate cyclases from both testes were mixed and assayed together, the activities were additive rather than exhibiting synergism or inhibition. These experiments indicate that the altered V(max) is not due to a transferable activator or inhibitor.An immunocytochemical technique was used to assess the cell type in which the alterations in cGMP metabolism occurred. Comparison of the scrotal and abdominal testes revealed that the abdominal testis exhibited enhanced cGMP immunofluorescence within the cells lining the inner aspect of the seminiferous tubule as well as tubular elements and interstitial cells. Thus, it is inferred that the correlated changes in soluble guanylate cyclase activity and cGMP levels occur in several of the cell types that remain viable within the cryptorchid testis."}
{"id": "PMID:29054", "title": "Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.", "content": "To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary  erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude.", "contents": "Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity. To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary  erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude."}
{"id": "PMID:29055", "title": "Direct evidence of participation of rat lung carbonic anhydrase in CO2 reactions.", "content": "Isolated rat lungs were ventilated with air and perfused with a blood-free Krebs-Ringer bicarbonate solution under conditions of net CO2 elimination in the lung. Some of the effluent perfusate was drawn through a stop-flow pH electrode apparatus, arriving at the electrode within 4 s after passing through the pulmonary capillaries. pH and temperature of the fluid in the electrode chamber were continuously monitored both before and after withdrawal was suddenly stopped. Little or no change was observed in the pH of the perfusate after flow was stopped, despite the fact that CO2 was eliminated in the lung, suggesting that the conversion of H2CO3 to CO2 in the blood-free perfusion fluid was markedly accelerated and the rise in pH was complete by the time the perfusate reached the electrode. Because the effluent perfusate was shown to be free of carbonic anhydrase activity, the catalysis must have occurred during transit through the isolated lung. When acetazolamide was added to the perfusate, a rise in the pH of the perfusate after stopping flow was consistently seen. These results suggest that the carbonic anhydrase of isolated lungs accelerates the conversion of H2CO3 to CO2 and enhances COW elimination as perfusate passes through the pulmonary capillaries, and that the enzyme may be present on the capillary endothelial surface.", "contents": "Direct evidence of participation of rat lung carbonic anhydrase in CO2 reactions. Isolated rat lungs were ventilated with air and perfused with a blood-free Krebs-Ringer bicarbonate solution under conditions of net CO2 elimination in the lung. Some of the effluent perfusate was drawn through a stop-flow pH electrode apparatus, arriving at the electrode within 4 s after passing through the pulmonary capillaries. pH and temperature of the fluid in the electrode chamber were continuously monitored both before and after withdrawal was suddenly stopped. Little or no change was observed in the pH of the perfusate after flow was stopped, despite the fact that CO2 was eliminated in the lung, suggesting that the conversion of H2CO3 to CO2 in the blood-free perfusion fluid was markedly accelerated and the rise in pH was complete by the time the perfusate reached the electrode. Because the effluent perfusate was shown to be free of carbonic anhydrase activity, the catalysis must have occurred during transit through the isolated lung. When acetazolamide was added to the perfusate, a rise in the pH of the perfusate after stopping flow was consistently seen. These results suggest that the carbonic anhydrase of isolated lungs accelerates the conversion of H2CO3 to CO2 and enhances COW elimination as perfusate passes through the pulmonary capillaries, and that the enzyme may be present on the capillary endothelial surface."}
{"id": "PMID:29056", "title": "Hereditary male pseudohermaphroditism associated with an unstable form of 5 alpha-reductase.", "content": "The properties of 5alpha-reductase have been compared in genital skin fibroblasts cultured from five patients from three families (Los Angeles, Dallas, and Dominican Republic) in which hereditary male pseudohermaphroditism has been established to result from deficient conversion of testosterone to dihydrotestosterone. Despite the fact that 5alpha-reductase was immeasurable in a homogenate of epididymis removed from one of the Los Angeles patients, 5alpha-reductase activity was normal in intact fibroblasts and fibroblast extracts from both patients from the Los Angeles family. Although the apparent K(m) for testosterone was also near normal, the apparent K(m) for NADPH in these mutants is elevated some 40-fold above normal. Furthermore, the enzyme is not protected against denaturation at 45 degrees C by concentrations of NADPH that stabilize normal 5alpha-reductase, and in intact fibroblasts from these patients (but not from controls), enzyme activity decreases promptly when protein synthesis is inhibited. We conclude that the mutation in this family results in an unstable enzyme. In contrast 5alpha-reductase activity in fibroblast extracts from a patient from the Dominican Republic family is similar to that previously described in two members of the Dallas family, namely total enzyme activity is low at the optimal pH for the normal reaction, and the apparent K(m) for testosterone is some 20-fold higher than that of the controls. We conclude that the mutations in the Dallas and Dominican Republic families are similar and result in low activity of the enzyme as the result of a decreased affinity for testosterone.Thus, two distinct types of mutations can produce male pseudohermaphroditism due to deficient dihydrotestosterone formation.", "contents": "Hereditary male pseudohermaphroditism associated with an unstable form of 5 alpha-reductase. The properties of 5alpha-reductase have been compared in genital skin fibroblasts cultured from five patients from three families (Los Angeles, Dallas, and Dominican Republic) in which hereditary male pseudohermaphroditism has been established to result from deficient conversion of testosterone to dihydrotestosterone. Despite the fact that 5alpha-reductase was immeasurable in a homogenate of epididymis removed from one of the Los Angeles patients, 5alpha-reductase activity was normal in intact fibroblasts and fibroblast extracts from both patients from the Los Angeles family. Although the apparent K(m) for testosterone was also near normal, the apparent K(m) for NADPH in these mutants is elevated some 40-fold above normal. Furthermore, the enzyme is not protected against denaturation at 45 degrees C by concentrations of NADPH that stabilize normal 5alpha-reductase, and in intact fibroblasts from these patients (but not from controls), enzyme activity decreases promptly when protein synthesis is inhibited. We conclude that the mutation in this family results in an unstable enzyme. In contrast 5alpha-reductase activity in fibroblast extracts from a patient from the Dominican Republic family is similar to that previously described in two members of the Dallas family, namely total enzyme activity is low at the optimal pH for the normal reaction, and the apparent K(m) for testosterone is some 20-fold higher than that of the controls. We conclude that the mutations in the Dallas and Dominican Republic families are similar and result in low activity of the enzyme as the result of a decreased affinity for testosterone.Thus, two distinct types of mutations can produce male pseudohermaphroditism due to deficient dihydrotestosterone formation."}
{"id": "PMID:29057", "title": "Taped vs. \"live\" desensitization and level of autonomic arousal.", "content": "Investigated whether variations in method of presentation of anxiety items (Es voice, E's taped voice, S's taped voice) will result in differences in autonomic arousal (as measured by self-report, galvanic skin responses, cardiac rate, blood pressure). Ss were 24 Naval Academy midshipmen. The procedure involved (1) training in deep muscle relaxation; and (2) measuring arousal after the presentation of anxiety-eliciting stimuli. Statistical analysis indicated that the influence of method of presentation was significant for galvanic skin response and self-reported anxiety. Comparison of cell means showed that verbal presentations were more effective in eliciting autonomic arousal than taped presentations. The results of this study provide partial evidence to support the conventional form of systematic desensitization as more effective than the newer automated or taped versions.", "contents": "Taped vs. \"live\" desensitization and level of autonomic arousal. Investigated whether variations in method of presentation of anxiety items (Es voice, E's taped voice, S's taped voice) will result in differences in autonomic arousal (as measured by self-report, galvanic skin responses, cardiac rate, blood pressure). Ss were 24 Naval Academy midshipmen. The procedure involved (1) training in deep muscle relaxation; and (2) measuring arousal after the presentation of anxiety-eliciting stimuli. Statistical analysis indicated that the influence of method of presentation was significant for galvanic skin response and self-reported anxiety. Comparison of cell means showed that verbal presentations were more effective in eliciting autonomic arousal than taped presentations. The results of this study provide partial evidence to support the conventional form of systematic desensitization as more effective than the newer automated or taped versions."}
{"id": "PMID:29060", "title": "Neuroleptic-induced attenuation of brain stimulation reward in rats.", "content": "In 30-min free-operant tests, the dopamine receptor blockers pimozide (.125, .25, and .50 mg/kg) and (+)-butaclamol (.1, .2, and .4 mg/kg) attenuated lever pressing for lateral hypothalamic brain stimulation. When discrete self-stimulation trials were offered in a straight alleyway, pimozide increased start box latencies, slowed running speeds, and reduced lever-pressing rates. However, performance early in both lever-pressing and runway sessions was normal; performance deteriorated as testing progressed, following patterns that paralleled those seen when animals were tested with reductions in the amplitude of stimulating current. Spontaneous recovery was obtained in both situations; experimenter-imposed 10-min time-outs caused renewed lever pressing and running. In contrast, alpha-noradrenergic receptor blockade by phenoxybenzamine (5, 10, and 20 mg/kg) failed to produce extinction-like response patterns. These data support the view that central dopaminergic systems are important components of the neural mechanisms mediating reward.", "contents": "Neuroleptic-induced attenuation of brain stimulation reward in rats. In 30-min free-operant tests, the dopamine receptor blockers pimozide (.125, .25, and .50 mg/kg) and (+)-butaclamol (.1, .2, and .4 mg/kg) attenuated lever pressing for lateral hypothalamic brain stimulation. When discrete self-stimulation trials were offered in a straight alleyway, pimozide increased start box latencies, slowed running speeds, and reduced lever-pressing rates. However, performance early in both lever-pressing and runway sessions was normal; performance deteriorated as testing progressed, following patterns that paralleled those seen when animals were tested with reductions in the amplitude of stimulating current. Spontaneous recovery was obtained in both situations; experimenter-imposed 10-min time-outs caused renewed lever pressing and running. In contrast, alpha-noradrenergic receptor blockade by phenoxybenzamine (5, 10, and 20 mg/kg) failed to produce extinction-like response patterns. These data support the view that central dopaminergic systems are important components of the neural mechanisms mediating reward."}
{"id": "PMID:29058", "title": "Effect of abdominal radiation therapy on drug absorption in humans.", "content": "The absorption of oral digoxin and of desmethyldiazepam, from its precursor clorazepate, was studied in seven patients who had received abdominal and/or pelvic radiation therapy for neoplastic disease. All patients were in remission and had normal renal function and no evidence of malabsorption. Single 0.5-mg doses of digoxin tablets and 15-mg doses of clorazepate were administered in the fasting state. Concentrations of digoxin (by radioimmunoassay) and desmethyldiazepam (by gas chromatography) were determined in multiple plasma samples and all urine collected during 24 hours after dosage. The mean (+/- S.E.) weight-normalized area under the 24-hour plasma digoxin concentration curve (WtN-AUC-24) in the patients (722 +/- 40 ng/ml-hr-kg) was similar to that in five normal controls (713 +/- 57 ng/ml-hr-kg), but 24-hour urinary excretion of digoxin in patients (54.5 +/- 4.4 microgram) was significantly less (P less than 0.025) than in controls (83.4 +/- 11.4 microgram). Neither age, sex, nor renal function explained the difference. In the clorazepate study, WtN-AUC-24 for desmethyldiazepam in the patients (187 +/- 19 microgram/ml-hr-kg) was significantly less (P less than 0.01) than in 15 normal control subjects (230 +/- 5 microgram/ml-hr-kg). Age and sex did not explain the difference. Thus, radiation therapy, or the underlying disease, is associated with malabsorption of these two drugs, possibly because of damage to gastric acid-secreting cells.", "contents": "Effect of abdominal radiation therapy on drug absorption in humans. The absorption of oral digoxin and of desmethyldiazepam, from its precursor clorazepate, was studied in seven patients who had received abdominal and/or pelvic radiation therapy for neoplastic disease. All patients were in remission and had normal renal function and no evidence of malabsorption. Single 0.5-mg doses of digoxin tablets and 15-mg doses of clorazepate were administered in the fasting state. Concentrations of digoxin (by radioimmunoassay) and desmethyldiazepam (by gas chromatography) were determined in multiple plasma samples and all urine collected during 24 hours after dosage. The mean (+/- S.E.) weight-normalized area under the 24-hour plasma digoxin concentration curve (WtN-AUC-24) in the patients (722 +/- 40 ng/ml-hr-kg) was similar to that in five normal controls (713 +/- 57 ng/ml-hr-kg), but 24-hour urinary excretion of digoxin in patients (54.5 +/- 4.4 microgram) was significantly less (P less than 0.025) than in controls (83.4 +/- 11.4 microgram). Neither age, sex, nor renal function explained the difference. In the clorazepate study, WtN-AUC-24 for desmethyldiazepam in the patients (187 +/- 19 microgram/ml-hr-kg) was significantly less (P less than 0.01) than in 15 normal control subjects (230 +/- 5 microgram/ml-hr-kg). Age and sex did not explain the difference. Thus, radiation therapy, or the underlying disease, is associated with malabsorption of these two drugs, possibly because of damage to gastric acid-secreting cells."}
{"id": "PMID:29068", "title": "Selective sensitivity to hydrocortisone of regulatory functions that determine the magnitude of the antibody response to type III pneumococcal polysaccharide.", "content": "Previous studies on the basis for the immunosuppressive potential of adrenal corticosteroids have stressed that the effects of these agents on immune functions depend on the animal species being considered, as well as the subpopulations of lymphocytes involved in the expression of immune functions examined. In the present work, we have evaluated the effect of a single dose of hydrocortisone on three different immunoregulatory functions that can influence the magnitude of an antibody response to Type III pneumococcal polysaccharide (SSS-III) in mice; these functions include suppressor, amplifier, and helper activity that are dependent upon the presence of distinct subpopulations of thymus-derived (T) cells. The results obtained show that a single injection of a relatively large dose of hydrocortisone, when given at the time of priming with carrier, eliminated all evidence of carrier-specific helper T cell activity; hydrocortisone was also found to eliminate a significant amount of helper T cell activity when given after such activity had been generated. But, under the same experimental conditions, suppressor and amplifier T cell activities were unaffected, even in this steroid-sensitive species. Such selective sensitivity may account for some of the immunosuppressive potency of steroids.", "contents": "Selective sensitivity to hydrocortisone of regulatory functions that determine the magnitude of the antibody response to type III pneumococcal polysaccharide. Previous studies on the basis for the immunosuppressive potential of adrenal corticosteroids have stressed that the effects of these agents on immune functions depend on the animal species being considered, as well as the subpopulations of lymphocytes involved in the expression of immune functions examined. In the present work, we have evaluated the effect of a single dose of hydrocortisone on three different immunoregulatory functions that can influence the magnitude of an antibody response to Type III pneumococcal polysaccharide (SSS-III) in mice; these functions include suppressor, amplifier, and helper activity that are dependent upon the presence of distinct subpopulations of thymus-derived (T) cells. The results obtained show that a single injection of a relatively large dose of hydrocortisone, when given at the time of priming with carrier, eliminated all evidence of carrier-specific helper T cell activity; hydrocortisone was also found to eliminate a significant amount of helper T cell activity when given after such activity had been generated. But, under the same experimental conditions, suppressor and amplifier T cell activities were unaffected, even in this steroid-sensitive species. Such selective sensitivity may account for some of the immunosuppressive potency of steroids."}
{"id": "PMID:29075", "title": "Hepatic lipid metabolism. Age-related changes in triglyceride metabolism.", "content": "Age-related changes in hepatic triglyceride formation have been described in developing rats. Triglyceride formation was measured in vitro in the presence of [14C]glycerol-3-phosphate, palmitate, ATP, CoA, and Mg2+ by using liver homogenates and microsomal fractions derived from various age groups of animals. Triglyceride formation was most active in one-day-old rats and then decrease with age. The increase in triglyceride formation following birth was prevented by the administration of puromycin or by denying suckling. In addition, changes in plasma and hepatic triglyceride concentrations, were also determined as functions of age. These studies suggest that the age of the animal significantly influences triglyceride metabolism.", "contents": "Hepatic lipid metabolism. Age-related changes in triglyceride metabolism. Age-related changes in hepatic triglyceride formation have been described in developing rats. Triglyceride formation was measured in vitro in the presence of [14C]glycerol-3-phosphate, palmitate, ATP, CoA, and Mg2+ by using liver homogenates and microsomal fractions derived from various age groups of animals. Triglyceride formation was most active in one-day-old rats and then decrease with age. The increase in triglyceride formation following birth was prevented by the administration of puromycin or by denying suckling. In addition, changes in plasma and hepatic triglyceride concentrations, were also determined as functions of age. These studies suggest that the age of the animal significantly influences triglyceride metabolism."}
{"id": "PMID:29076", "title": "R-factor mediated dihydrofolate reductases which confer trimethoprim resistance.", "content": "Six different R-factors conferring trimethoprim resistance had been isolated from a variety of sources. The trimethoprim-resistant dihydrofolate reductases (EC 1.5.1.3) from strains containing these R-factors were purified by ammonium sulphate precipitation and DEAE-cellulose ion-exchange chromatography. The enzymes showed no significant differences in molecular weight, pH profile, substrate profile, heat sensitivity, inhibition profile and Michaelis-Menten kinetics. There was, however, considerable variation in the specific activity of these enzymes in the same bacterial host. When two Escherichia coli trimethoprimsensitive dihydrofolate reductases were examined as controls, considerable differences between their properties and those of the enzymes mediated by R-factors were detected. The data suggest that one trimethoprim resistance gene could be spreading through the bacterial population, possibly situated on a transposon.", "contents": "R-factor mediated dihydrofolate reductases which confer trimethoprim resistance. Six different R-factors conferring trimethoprim resistance had been isolated from a variety of sources. The trimethoprim-resistant dihydrofolate reductases (EC 1.5.1.3) from strains containing these R-factors were purified by ammonium sulphate precipitation and DEAE-cellulose ion-exchange chromatography. The enzymes showed no significant differences in molecular weight, pH profile, substrate profile, heat sensitivity, inhibition profile and Michaelis-Menten kinetics. There was, however, considerable variation in the specific activity of these enzymes in the same bacterial host. When two Escherichia coli trimethoprimsensitive dihydrofolate reductases were examined as controls, considerable differences between their properties and those of the enzymes mediated by R-factors were detected. The data suggest that one trimethoprim resistance gene could be spreading through the bacterial population, possibly situated on a transposon."}
{"id": "PMID:29077", "title": "An RNA polymerase activity in purified rabies virions.", "content": "An RNA polymerase activity has been demonstrated in purified rabies virions. Efficiency of the reaction is low since the rate of incorporation was equal to 3 to 5 pmol of uridine per hour, per mg of protein. As with other mammalian rhabdoviruses the optimal temperature was 31 degrees C. Unlike vesicular stomatitis virus, manganese could be substituted for magnesium as a divalent cation, at an optimum concentration of 10 to 20 mM.", "contents": "An RNA polymerase activity in purified rabies virions. An RNA polymerase activity has been demonstrated in purified rabies virions. Efficiency of the reaction is low since the rate of incorporation was equal to 3 to 5 pmol of uridine per hour, per mg of protein. As with other mammalian rhabdoviruses the optimal temperature was 31 degrees C. Unlike vesicular stomatitis virus, manganese could be substituted for magnesium as a divalent cation, at an optimum concentration of 10 to 20 mM."}
{"id": "PMID:29078", "title": "Increase by calcium in production of interferon by L929 cells induced with polyriboinosinate-polyribocytidylate complex.", "content": "Calcium chloride (5 to 20 mM) potentiated interferon production induced by rIn:rCn in L929 mouse fibroblasts up to a thousand-fold. Higher concentrations of calcium (20 to 65 mM) mixed with rIn:rCn were associated with increased cytotoxicity and a more acidic medium, but were effective in enhancing interferon production if preparations were adjusted to a uniform pH. Although calcium increased cellular binding of 3H-rCn:rIn, only a partial correlation between binding and interferon production was observed.", "contents": "Increase by calcium in production of interferon by L929 cells induced with polyriboinosinate-polyribocytidylate complex. Calcium chloride (5 to 20 mM) potentiated interferon production induced by rIn:rCn in L929 mouse fibroblasts up to a thousand-fold. Higher concentrations of calcium (20 to 65 mM) mixed with rIn:rCn were associated with increased cytotoxicity and a more acidic medium, but were effective in enhancing interferon production if preparations were adjusted to a uniform pH. Although calcium increased cellular binding of 3H-rCn:rIn, only a partial correlation between binding and interferon production was observed."}
{"id": "PMID:29079", "title": "Poly (A) polymerase activity in L cells following encephalomyocarditis virus infection.", "content": "Poly (A) polymerase activity has been measured in crude cytoplasmic extracts of mouse L cells infected with encephalomyocarditis (EMC) virus. After infection there is first a decrease in enzyme activity followed by an increase which itself precedes detectable virus RNA and protein synthesis. The activity of the enzyme then declines before the release of mature virions and cell death take place. The early inhibition of poly (A) polymerase activity is correlated with the virus-induced shut-off of cellular protein synthesis but it is not due to inhibition of the synthesis of cellular enzyme and occurs in the absence of virus replication. The poly (A) polymerase is not synthesized after infection and modification of its activity can be reversed late in the virus cycle. These results indicate that host poly (A) polymerase activity can be regulated by the virus and further show that there is a correlation between the modification of poly (A) polymerase activity and the biosynthesis of poly (A).", "contents": "Poly (A) polymerase activity in L cells following encephalomyocarditis virus infection. Poly (A) polymerase activity has been measured in crude cytoplasmic extracts of mouse L cells infected with encephalomyocarditis (EMC) virus. After infection there is first a decrease in enzyme activity followed by an increase which itself precedes detectable virus RNA and protein synthesis. The activity of the enzyme then declines before the release of mature virions and cell death take place. The early inhibition of poly (A) polymerase activity is correlated with the virus-induced shut-off of cellular protein synthesis but it is not due to inhibition of the synthesis of cellular enzyme and occurs in the absence of virus replication. The poly (A) polymerase is not synthesized after infection and modification of its activity can be reversed late in the virus cycle. These results indicate that host poly (A) polymerase activity can be regulated by the virus and further show that there is a correlation between the modification of poly (A) polymerase activity and the biosynthesis of poly (A)."}
{"id": "PMID:29080", "title": "Cerebral transmitter precursors and metabolites in advanced renal disease.", "content": "Patients with chronic renal disease had low plasma total tryptophan but an abnormally high proportion of this was in the free state. The subjects with encephalopathy had raised plasma free tryptophan, CSF tryptophan, and CSF 5-hydroxyindoleacetic acid. CSF tryptophan correlated better with plasma free than with plasma total tryptophan. Plasma and CSF tyrosine concentrations were normal but CSF homovanillic acid was raised especially in subjects with encephalopathy. The possible significance of these changes in advanced renal disease is discussed.", "contents": "Cerebral transmitter precursors and metabolites in advanced renal disease. Patients with chronic renal disease had low plasma total tryptophan but an abnormally high proportion of this was in the free state. The subjects with encephalopathy had raised plasma free tryptophan, CSF tryptophan, and CSF 5-hydroxyindoleacetic acid. CSF tryptophan correlated better with plasma free than with plasma total tryptophan. Plasma and CSF tyrosine concentrations were normal but CSF homovanillic acid was raised especially in subjects with encephalopathy. The possible significance of these changes in advanced renal disease is discussed."}
{"id": "PMID:29081", "title": "Guanylate cyclase activity in normal and diseased human muscle.", "content": "Guanylate cyclase activity has been studied in muscle of normal subjects and of patients suffering from muscular and neuromuscular diseases. In normal tissue a guanylate cyclase activity was found in both soluble and particulate fractions of homogenate. We found also that the kinetic analysis of the enzyme of soluble differed from that of particulate fraction. A decrease of guanylate cyclase activity in crude homogenate was observed in muscular dystrophies, in neuromuscular atrophies, and in inflammatory forms of muscle disease.", "contents": "Guanylate cyclase activity in normal and diseased human muscle. Guanylate cyclase activity has been studied in muscle of normal subjects and of patients suffering from muscular and neuromuscular diseases. In normal tissue a guanylate cyclase activity was found in both soluble and particulate fractions of homogenate. We found also that the kinetic analysis of the enzyme of soluble differed from that of particulate fraction. A decrease of guanylate cyclase activity in crude homogenate was observed in muscular dystrophies, in neuromuscular atrophies, and in inflammatory forms of muscle disease."}
{"id": "PMID:29083", "title": "Neurosurgery: considerations for strength and quality. The 1978 AANS presidential address.", "content": "The President of the American Association of Neurological Surgeons reviews the organization of the Association designed to represent neurosurgery and neurosurgeons. He summarizes the pertinent problems that the specialty has faced and with which it continues to deal, in persistent pursuit of its objective: to assure the highest quality of neurosurgical care for all.", "contents": "Neurosurgery: considerations for strength and quality. The 1978 AANS presidential address. The President of the American Association of Neurological Surgeons reviews the organization of the Association designed to represent neurosurgery and neurosurgeons. He summarizes the pertinent problems that the specialty has faced and with which it continues to deal, in persistent pursuit of its objective: to assure the highest quality of neurosurgical care for all."}
{"id": "PMID:29085", "title": "Selective defect of precursor T cells associated with apparently normal B lymphocytes in severe combined immunodeficiency disease.", "content": "Two patients, one with an autosomal and the other a sex-linked form of severe combined immunodeficiency, had more than 95% B cells in their peripheral blood. Despite an increased absolute number of B lymphocytes, the patients were unable to produce serum antibodies. In each patient, geno- or pheno-identical bone marrow transplantation was followed by the visualization of a thymus shadow and the appearance of both cellular and humoral functions. Chromosome of allotype studies showed that the T cell originated from the donor whereas serum immunoglobulins were synthesized by host B cells. In these patients the pathogenesis appears to be a selective defect of bone marrow precursor T cells without concomitant intrinsic B cell defect. The successful outcome of the graft in these two patients, who are now, respectively, 5 years and 11 months of age and free of infections, indicates that the preferred form of therapy in such patients is transplantation of bone marrow stem cells, which populate the thymus and mature slowly into T cells that cooperate fully with host B cells in synthesis of antibody.", "contents": "Selective defect of precursor T cells associated with apparently normal B lymphocytes in severe combined immunodeficiency disease. Two patients, one with an autosomal and the other a sex-linked form of severe combined immunodeficiency, had more than 95% B cells in their peripheral blood. Despite an increased absolute number of B lymphocytes, the patients were unable to produce serum antibodies. In each patient, geno- or pheno-identical bone marrow transplantation was followed by the visualization of a thymus shadow and the appearance of both cellular and humoral functions. Chromosome of allotype studies showed that the T cell originated from the donor whereas serum immunoglobulins were synthesized by host B cells. In these patients the pathogenesis appears to be a selective defect of bone marrow precursor T cells without concomitant intrinsic B cell defect. The successful outcome of the graft in these two patients, who are now, respectively, 5 years and 11 months of age and free of infections, indicates that the preferred form of therapy in such patients is transplantation of bone marrow stem cells, which populate the thymus and mature slowly into T cells that cooperate fully with host B cells in synthesis of antibody."}
{"id": "PMID:29089", "title": "The effect of microcapsule size on the oxidative decomposition of core material.", "content": "The factors that affect the size of microcapsules and the oxidation of their benzaldehyde core have been examined. The pH of the preparation changed the overall size of the microcapsules which reached a maximum diameter at pH 4.1. The size of the core droplets also varied with the preparative pH and their oxidation rate depended on the bulk droplet size rather than their surface area. A rapid oxidation of benzaldehyde associated with the microcapsule wall resulted in a preliminary peak in the oxidation curve. Explanations for these phenomena are discussed.", "contents": "The effect of microcapsule size on the oxidative decomposition of core material. The factors that affect the size of microcapsules and the oxidation of their benzaldehyde core have been examined. The pH of the preparation changed the overall size of the microcapsules which reached a maximum diameter at pH 4.1. The size of the core droplets also varied with the preparative pH and their oxidation rate depended on the bulk droplet size rather than their surface area. A rapid oxidation of benzaldehyde associated with the microcapsule wall resulted in a preliminary peak in the oxidation curve. Explanations for these phenomena are discussed."}
{"id": "PMID:29090", "title": "The wetting of powders of acetylsalicylic acid, salicylic acid, phenacetin and paracetamol.", "content": "The wetting of powders of acetylsalicylic acid, salicylic acid, phenacetin and paracetamol has been assessed using methanol--water mixtures to give a range of surface tensions. The results have been interpreted in terms of the critical surface tension, adhesion tension and spreading coefficients. The critical surface tension values are surprisingly low which may be due to adsorption of the methanol at the solid surface, exposing its CH3 group to the liquid. The adhesion tension and spreading coefficient values could be useful guides in formulation.", "contents": "The wetting of powders of acetylsalicylic acid, salicylic acid, phenacetin and paracetamol. The wetting of powders of acetylsalicylic acid, salicylic acid, phenacetin and paracetamol has been assessed using methanol--water mixtures to give a range of surface tensions. The results have been interpreted in terms of the critical surface tension, adhesion tension and spreading coefficients. The critical surface tension values are surprisingly low which may be due to adsorption of the methanol at the solid surface, exposing its CH3 group to the liquid. The adhesion tension and spreading coefficient values could be useful guides in formulation."}
{"id": "PMID:29091", "title": "Structure activity relation for some 1,4-benzodiazepinones: correlation between rate constants for reduction by sodium borohydride and antileptazol ED50.", "content": "Significant correlation in 11 different 1,4-benzodiazepinones has been established between log k2 (the second order rate constant for the reduction of the \"azepinones\" by sodium borohydride) and their ED50 against leptazol-induced seizures in mice. The results suggest a possible involvement of the carobnyl group at the receptor site.", "contents": "Structure activity relation for some 1,4-benzodiazepinones: correlation between rate constants for reduction by sodium borohydride and antileptazol ED50. Significant correlation in 11 different 1,4-benzodiazepinones has been established between log k2 (the second order rate constant for the reduction of the \"azepinones\" by sodium borohydride) and their ED50 against leptazol-induced seizures in mice. The results suggest a possible involvement of the carobnyl group at the receptor site."}
{"id": "PMID:29092", "title": "The use of 13C-nmr spectroscopy for the detection and identification of metabolites of carbon-13 labelled amitriptyline.", "content": "The antidepressant drug amitriptyline and two of its metabolites, nortriptyline and desmethylnortriptyline, each containing two 13C atoms, have been used to determine the sensitivity and selectivity of 13C-nmr spectroscopy for the detection of unchanged amitriptyline and N-desmethyl metabolites in the urine of animals dosed orally with the labelled drug. The resonance signals from the 13C atoms detected in the 13C-nmr spectrum of entire extract from a control 12 h rat urine sample to which 1 mg of each labelled compound had been added were easily detected, using an instrument accumulation time of 1 h. The 13C-nmr spectrum of an extract of hydrolysed urine from a dog that had received an oral dose of  [13C2]amitriptyline (30mg) exhibited signals that could be assigned to metabolites resulting from N-dealkylation and N-oxidation, as well as those bearing the intact amitriptyline side-chain. These assignments were confirmed by analysis of the same extract by g.c.--ms and h.p.l.c.", "contents": "The use of 13C-nmr spectroscopy for the detection and identification of metabolites of carbon-13 labelled amitriptyline. The antidepressant drug amitriptyline and two of its metabolites, nortriptyline and desmethylnortriptyline, each containing two 13C atoms, have been used to determine the sensitivity and selectivity of 13C-nmr spectroscopy for the detection of unchanged amitriptyline and N-desmethyl metabolites in the urine of animals dosed orally with the labelled drug. The resonance signals from the 13C atoms detected in the 13C-nmr spectrum of entire extract from a control 12 h rat urine sample to which 1 mg of each labelled compound had been added were easily detected, using an instrument accumulation time of 1 h. The 13C-nmr spectrum of an extract of hydrolysed urine from a dog that had received an oral dose of  [13C2]amitriptyline (30mg) exhibited signals that could be assigned to metabolites resulting from N-dealkylation and N-oxidation, as well as those bearing the intact amitriptyline side-chain. These assignments were confirmed by analysis of the same extract by g.c.--ms and h.p.l.c."}
{"id": "PMID:29093", "title": "Acidic in vivo metabolites of cannabinol isolated from rat faeces.", "content": "Six acidic metabolites were isolated from rat faeces and identified by gas chromatographymass spectrometry and proton magnetic resonance. Cannabinol-7-oic acid was the most abundant acidic metabolite isolated. Others present in decreasing order of prominence were 1\"-hydroxy-, 4\"-hydroxy-, 3\"-hydroxycannabinol-7-oic acid, cannabinol-3\"-one-7-oic acid and 2\"-hydroxycannabinol-7-oic acid.", "contents": "Acidic in vivo metabolites of cannabinol isolated from rat faeces. Six acidic metabolites were isolated from rat faeces and identified by gas chromatographymass spectrometry and proton magnetic resonance. Cannabinol-7-oic acid was the most abundant acidic metabolite isolated. Others present in decreasing order of prominence were 1\"-hydroxy-, 4\"-hydroxy-, 3\"-hydroxycannabinol-7-oic acid, cannabinol-3\"-one-7-oic acid and 2\"-hydroxycannabinol-7-oic acid."}
{"id": "PMID:29094", "title": "Comparison between spontaneously beating atria from control and streptozocin-diabetic rats.", "content": "Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5.6 to 27 mM resulted in decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 mM 2-deoxyglucose, 10(-3) i.u. insulin ml-1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2-deoxyglucose but increased by insulin. 2-Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.", "contents": "Comparison between spontaneously beating atria from control and streptozocin-diabetic rats. Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5.6 to 27 mM resulted in decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 mM 2-deoxyglucose, 10(-3) i.u. insulin ml-1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2-deoxyglucose but increased by insulin. 2-Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed."}
{"id": "PMID:29095", "title": "The antitussive actions of the drug Ru 20201 given as an aerosol to cats.", "content": "The effect of the drug Ru 20201 (1,2,3,4,4a,9b-hexahydro,-8,9b-dimethyl-4-[3-(4-methylpiperazin-1-yl)propionamido]dibenzofuran-3-one upon mechanically-evoked cough from the laryngopharyngeal and tracheobronchial areas in nine unanaesthetized cats has been examined. Inhalation of 2 ml of an aerosol of a 10% solution in water suppressed coughing for 30 min. The effect was greatest on the number of cough efforts. The expiratory component of cough was suppressed more than was the inspiratory one. The effect was greater on cough from the laryngopharyngeal than from the tracheobronchial area.", "contents": "The antitussive actions of the drug Ru 20201 given as an aerosol to cats. The effect of the drug Ru 20201 (1,2,3,4,4a,9b-hexahydro,-8,9b-dimethyl-4-[3-(4-methylpiperazin-1-yl)propionamido]dibenzofuran-3-one upon mechanically-evoked cough from the laryngopharyngeal and tracheobronchial areas in nine unanaesthetized cats has been examined. Inhalation of 2 ml of an aerosol of a 10% solution in water suppressed coughing for 30 min. The effect was greatest on the number of cough efforts. The expiratory component of cough was suppressed more than was the inspiratory one. The effect was greater on cough from the laryngopharyngeal than from the tracheobronchial area."}
{"id": "PMID:29114", "title": "Characterization of pharmacologically important prototropic species derived from a pyridinemethanol antimalarial by electronic absorption and fluorescence spectroscopy.", "content": "Variations of the absorption and fluorescence spectra of the experimental antimalarial drug, alpha-dibutylaminomethyl-2,6-bis(p-trifluoromethylphenyl)-4-pyridinemethanol, were investigated throughout the pH region in concentrated sulfuric acid media and in n-hexane. The predominant prototropic species at physiological pH is the singly charged cation. In the pH 6--12 region, the structured fluorescence of the monocation is quenched with the concomitant appearance of a diffuse, long wavelength emission while the corresponding absorption spectra shift only slightly to longer wavelengths. Furthermore, the dibutylamino group exhibits an unusually low basicity. This behavior is explained as due to the formation of an intramolecular hydrogen bond in the neutral molecule in the ground and lowest excited singlet states. A similar intramolecular hydrogen bond in the monocation is not spectroscopically visible.", "contents": "Characterization of pharmacologically important prototropic species derived from a pyridinemethanol antimalarial by electronic absorption and fluorescence spectroscopy. Variations of the absorption and fluorescence spectra of the experimental antimalarial drug, alpha-dibutylaminomethyl-2,6-bis(p-trifluoromethylphenyl)-4-pyridinemethanol, were investigated throughout the pH region in concentrated sulfuric acid media and in n-hexane. The predominant prototropic species at physiological pH is the singly charged cation. In the pH 6--12 region, the structured fluorescence of the monocation is quenched with the concomitant appearance of a diffuse, long wavelength emission while the corresponding absorption spectra shift only slightly to longer wavelengths. Furthermore, the dibutylamino group exhibits an unusually low basicity. This behavior is explained as due to the formation of an intramolecular hydrogen bond in the neutral molecule in the ground and lowest excited singlet states. A similar intramolecular hydrogen bond in the monocation is not spectroscopically visible."}
{"id": "PMID:29115", "title": "pH-solubility profiles or organic carboxylic acids and their salts.", "content": "The solubilities of naproxen, 7-methylsulfinyl-2-xanthonecarboxylic acid, 7-methylthio-2-xanthonecarboxylic acid, and their sodium, potassium, calcium, and magnesium salts were determined as a function of pH. The results on the solubility of naproxen and its salts were in excellent agreement with the theoretical profiles describing the relationship between pH values of the solutions and the dissociation constant of the acid. The solubilities of the two xanthonecarboxylic acids were higher at higher pH values than the values calculated when complete dissociation in solution was assumed. The influence of the salt species on the solubility of organic carboxylic acids, at and above pH values of complete ionization, cannot be predicted even qualitatively from equations used for alkali and alkaline earth metal salts.", "contents": "pH-solubility profiles or organic carboxylic acids and their salts. The solubilities of naproxen, 7-methylsulfinyl-2-xanthonecarboxylic acid, 7-methylthio-2-xanthonecarboxylic acid, and their sodium, potassium, calcium, and magnesium salts were determined as a function of pH. The results on the solubility of naproxen and its salts were in excellent agreement with the theoretical profiles describing the relationship between pH values of the solutions and the dissociation constant of the acid. The solubilities of the two xanthonecarboxylic acids were higher at higher pH values than the values calculated when complete dissociation in solution was assumed. The influence of the salt species on the solubility of organic carboxylic acids, at and above pH values of complete ionization, cannot be predicted even qualitatively from equations used for alkali and alkaline earth metal salts."}
{"id": "PMID:29117", "title": "Synthesis and beta-adrenergic blocking action of a new thiazolylthiopropanolamine derivative.", "content": "The synthesis of (+/-)-2-(3'-tert-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'-thienyl)thiazole hydrochloride is described. The new compound antagonized the cardiovascular effects, such as positive chronotropic, positive inotropic, or depressor arterial blood pressure responses, elicited by intravenous isoproterenol; it was 9--14 times as potent as propranolol in anesthetized open chest dogs. The oral administration of the compound reduced isoproterenol tachycardia in conscious dogs. It was about five times as potent as propranolol in this test, with maximal action after 1 hr, and its duration was significantly longer than that of propranolol.", "contents": "Synthesis and beta-adrenergic blocking action of a new thiazolylthiopropanolamine derivative. The synthesis of (+/-)-2-(3'-tert-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'-thienyl)thiazole hydrochloride is described. The new compound antagonized the cardiovascular effects, such as positive chronotropic, positive inotropic, or depressor arterial blood pressure responses, elicited by intravenous isoproterenol; it was 9--14 times as potent as propranolol in anesthetized open chest dogs. The oral administration of the compound reduced isoproterenol tachycardia in conscious dogs. It was about five times as potent as propranolol in this test, with maximal action after 1 hr, and its duration was significantly longer than that of propranolol."}
{"id": "PMID:29118", "title": "GLC determination of atenolol and beta-blocking agents in biological fluids.", "content": "A rapid, sensitive, and specific method of analysis for atenolol is described. Metoprolol is used as the internal standard. Atenolol and metoprolol are extracted into 1-butanol--benzene. Interfering components present in palsma and urine, but not discolored saliva, are removed during an acid wash and reextraction into ether. Drug and internal standard are converted to the pentafluoropropionate derivatives, which are quantitated by GLC with electron-capture detection and characterized by chemical-ionization mass spectrometry. The method should be applicable to measurement of other beta-adrenergic blocking agents with similar structures.", "contents": "GLC determination of atenolol and beta-blocking agents in biological fluids. A rapid, sensitive, and specific method of analysis for atenolol is described. Metoprolol is used as the internal standard. Atenolol and metoprolol are extracted into 1-butanol--benzene. Interfering components present in palsma and urine, but not discolored saliva, are removed during an acid wash and reextraction into ether. Drug and internal standard are converted to the pentafluoropropionate derivatives, which are quantitated by GLC with electron-capture detection and characterized by chemical-ionization mass spectrometry. The method should be applicable to measurement of other beta-adrenergic blocking agents with similar structures."}
{"id": "PMID:29119", "title": "An ATPase dependent, radiosensitive acidic microclimate essential for intestinal folate absorption.", "content": "1. 5-Methyltetrahydrofolic acid transport was studied across everted sacs of rat jejunal segments from control and whole body X-irradiated (700 rad) rats at 10(-5)M concentrations (at which optimum transport occurs) at various pHs.2. The folate transport from mucosal to serosal compartment was inhibited by about 55% in irradiated rat at the pH of the intestinal chyme (6.5). Extraneous ATP in the incubation system could restore the defective transport of the irradiated intestine.3. The maximum folate transport which occurred at pH 4.0 was not adversely affected by whole body irradiation. An acidic, pH dependent, passive uptake of 5-methyltetrahydrofolic acid was observed.4. The normal absorption barrier of the small bowel was not disrupted by the acidification process as practically no uptake was observed with irradiated segments pretreated at pH 4.0 except in the presence of ATP.5. Leucine and serine transport at a zero concentration gradient indicated active transport mechanisms which were not affected by acidification. Their uptake was additively increased in the presence of glucose and ATP, further indicating that the normal physiology of the intestines was not affected by the acidification process.6. An intestinal mucosal cell surface ATPase was observed which was Mg(2+) dependent. It could hydrolyse solution phase ATP and thus generate the protons necessary for the acidification of a microenvironment where passive uptake of the neutral folate species could occur.7. The ATPase activity was inhibited about 90% by 50 mM-Na azide at pH 6.5. Below this concentration folate transport was also inhibited.8. Na azide did not inhibit folate transport at pH 4.0, suggesting that its inhibition of folate uptake at pH 6.5 is related to its inhibitory effect on ATPase, rather than on folate transport per se. ATPase activity was therefore essential for folate transport at the pH of the intestinal chyme.", "contents": "An ATPase dependent, radiosensitive acidic microclimate essential for intestinal folate absorption. 1. 5-Methyltetrahydrofolic acid transport was studied across everted sacs of rat jejunal segments from control and whole body X-irradiated (700 rad) rats at 10(-5)M concentrations (at which optimum transport occurs) at various pHs.2. The folate transport from mucosal to serosal compartment was inhibited by about 55% in irradiated rat at the pH of the intestinal chyme (6.5). Extraneous ATP in the incubation system could restore the defective transport of the irradiated intestine.3. The maximum folate transport which occurred at pH 4.0 was not adversely affected by whole body irradiation. An acidic, pH dependent, passive uptake of 5-methyltetrahydrofolic acid was observed.4. The normal absorption barrier of the small bowel was not disrupted by the acidification process as practically no uptake was observed with irradiated segments pretreated at pH 4.0 except in the presence of ATP.5. Leucine and serine transport at a zero concentration gradient indicated active transport mechanisms which were not affected by acidification. Their uptake was additively increased in the presence of glucose and ATP, further indicating that the normal physiology of the intestines was not affected by the acidification process.6. An intestinal mucosal cell surface ATPase was observed which was Mg(2+) dependent. It could hydrolyse solution phase ATP and thus generate the protons necessary for the acidification of a microenvironment where passive uptake of the neutral folate species could occur.7. The ATPase activity was inhibited about 90% by 50 mM-Na azide at pH 6.5. Below this concentration folate transport was also inhibited.8. Na azide did not inhibit folate transport at pH 4.0, suggesting that its inhibition of folate uptake at pH 6.5 is related to its inhibitory effect on ATPase, rather than on folate transport per se. ATPase activity was therefore essential for folate transport at the pH of the intestinal chyme."}
{"id": "PMID:29123", "title": "beta-Adrenergic blocking agents. 18. 1-(Aryloxy)-3-(arylthioalkylamino)propan-2-ols and 1-substituted alkylthioamino-3-(aryloxy)propan-2-ols.", "content": "The synthesis is described of a seris of derivaties of 1-(aryloxy)-3-(arylthioalkylamiho)propan-2-ols and 1-(alkylthioamino)- and 1-(aralkylamino)-3-(aryloxy)propan-2-ols. These compounds were investigated for their beta-adrenoreceptor blocking properties and their selectivity of action for the cardiac beta1 receptor. The structure-activity relationships are discussed with particular reference to the effects of the sulfur, sulfoxide, and sulfone groups on beta-adrenoreceptor blocking potency and selectivity.", "contents": "beta-Adrenergic blocking agents. 18. 1-(Aryloxy)-3-(arylthioalkylamino)propan-2-ols and 1-substituted alkylthioamino-3-(aryloxy)propan-2-ols. The synthesis is described of a seris of derivaties of 1-(aryloxy)-3-(arylthioalkylamiho)propan-2-ols and 1-(alkylthioamino)- and 1-(aralkylamino)-3-(aryloxy)propan-2-ols. These compounds were investigated for their beta-adrenoreceptor blocking properties and their selectivity of action for the cardiac beta1 receptor. The structure-activity relationships are discussed with particular reference to the effects of the sulfur, sulfoxide, and sulfone groups on beta-adrenoreceptor blocking potency and selectivity."}
{"id": "PMID:29124", "title": "A series of hexahydro[1,4]oxazino[3,4-a]isoquinolines as potential neuroleptics.", "content": "The synthesis and stereochemistry of trans-N,N-diethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro[1,4]oxazino[3,4-a]isoquinoline-3-carboxamide hydrochloride (16) and a series of analogues are described. 16 and its (+) isomer had neuroleptic properties in the Sidman avoidance test in gerbils. A few closely related amides of the trans series were active but cis amides were inactive as neuroleptics.", "contents": "A series of hexahydro[1,4]oxazino[3,4-a]isoquinolines as potential neuroleptics. The synthesis and stereochemistry of trans-N,N-diethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro[1,4]oxazino[3,4-a]isoquinoline-3-carboxamide hydrochloride (16) and a series of analogues are described. 16 and its (+) isomer had neuroleptic properties in the Sidman avoidance test in gerbils. A few closely related amides of the trans series were active but cis amides were inactive as neuroleptics."}
{"id": "PMID:29125", "title": "Facile syntheses of potent dopaminergic argonists and their effect on neurotransmitter release.", "content": "The facile syntheses of important intermediates used in the preparation of the two potent dopaminergic argonists, 2-amino-6,7-dihydroxytetrahydronaphthalene (11) (referred to by some authors as ADTN) and its 5,6-dihydroxyl isomer 12, are described. Thus 6,7-dimethyoxy-2-tetralone has been prepared in two steps and 5,6-dimethoxy-2-tetralone in three steps both from commercially available materials. The effects of 11, 12, and the noncatechol analogue, 2-aminotetrahydronaphthalene (ATN), on radioactive neurotransmitter release have been studied in vitro using rat brain slices. It has been shown that both 11 and 12, at a concentraiton of 2 micron, cause a release of [3H]-DA and NA, 11 being more potent than 12 in releasing [3H]-DA. ATN (2 micron) was found to be inactive in these experiments which shows the importance of the catechol function in this uptake--release process.", "contents": "Facile syntheses of potent dopaminergic argonists and their effect on neurotransmitter release. The facile syntheses of important intermediates used in the preparation of the two potent dopaminergic argonists, 2-amino-6,7-dihydroxytetrahydronaphthalene (11) (referred to by some authors as ADTN) and its 5,6-dihydroxyl isomer 12, are described. Thus 6,7-dimethyoxy-2-tetralone has been prepared in two steps and 5,6-dimethoxy-2-tetralone in three steps both from commercially available materials. The effects of 11, 12, and the noncatechol analogue, 2-aminotetrahydronaphthalene (ATN), on radioactive neurotransmitter release have been studied in vitro using rat brain slices. It has been shown that both 11 and 12, at a concentraiton of 2 micron, cause a release of [3H]-DA and NA, 11 being more potent than 12 in releasing [3H]-DA. ATN (2 micron) was found to be inactive in these experiments which shows the importance of the catechol function in this uptake--release process."}
{"id": "PMID:29126", "title": "Synthesis and biologic distribution of radioiodinated beta-adrenergic antagonists.", "content": "Iodinated analogues 2, 7, and 8 were prepared from propranolol, practolol, and acebutolol in 30--50% yields. Radioisotopic exchange between carrier-free Na125I and the molten iodinated beta-adrenergic antagonist yielded the corresponding 125I-labeled product. The biodistribution in rats, determined at 15 and 60 min postinjection, indicated that the radioiodinated analogues of the cardioselective drugs practolol and acebutolol localized to a greater degree in the liver and heart than the analogue of propranolol. Conversely, [125I]iodopropranolol (2) was concentrated to a greater extent in the lungs than [125I]iodopractolol (7) or [125I]iodoacebutolol (8). Therefore, 123I- or 131I-labeled cardioselective beta-adrenergic antagonists, such as 7 or 8, may prove useful as radiodiagnostic agents for the external imaging of the myocardium.", "contents": "Synthesis and biologic distribution of radioiodinated beta-adrenergic antagonists. Iodinated analogues 2, 7, and 8 were prepared from propranolol, practolol, and acebutolol in 30--50% yields. Radioisotopic exchange between carrier-free Na125I and the molten iodinated beta-adrenergic antagonist yielded the corresponding 125I-labeled product. The biodistribution in rats, determined at 15 and 60 min postinjection, indicated that the radioiodinated analogues of the cardioselective drugs practolol and acebutolol localized to a greater degree in the liver and heart than the analogue of propranolol. Conversely, [125I]iodopropranolol (2) was concentrated to a greater extent in the lungs than [125I]iodopractolol (7) or [125I]iodoacebutolol (8). Therefore, 123I- or 131I-labeled cardioselective beta-adrenergic antagonists, such as 7 or 8, may prove useful as radiodiagnostic agents for the external imaging of the myocardium."}
{"id": "PMID:29132", "title": "The formation of peptides from the 2'(3')-glycyl ester of a nucleotide.", "content": "We have synthesized 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate), an analogue of the 3'-terminus of aminoacylated tRNA. A 0.4M solution of this compound maintained at pH 8.2, yields 5.5% of diglycine and 11.5% of diketopiperazine, in addition to the hydrolysis products glycine and adenosine-5'-(O-methylphosphate). Under the same conditions, glycine ethyl ester reacts much more slowly, but ultimately gives similar yields of diglycine and diketopiperazine. The aminolysis of 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate) by free glycine is relatively inefficient, but serine reacts 20 times more rapidly and yields up to 50% of N-glycylserine. The prebiotic significance of these reactions is discussed.", "contents": "The formation of peptides from the 2'(3')-glycyl ester of a nucleotide. We have synthesized 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate), an analogue of the 3'-terminus of aminoacylated tRNA. A 0.4M solution of this compound maintained at pH 8.2, yields 5.5% of diglycine and 11.5% of diketopiperazine, in addition to the hydrolysis products glycine and adenosine-5'-(O-methylphosphate). Under the same conditions, glycine ethyl ester reacts much more slowly, but ultimately gives similar yields of diglycine and diketopiperazine. The aminolysis of 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate) by free glycine is relatively inefficient, but serine reacts 20 times more rapidly and yields up to 50% of N-glycylserine. The prebiotic significance of these reactions is discussed."}
{"id": "PMID:29133", "title": "Muscarinic cholinergic activation of mouse spleen cells cytotoxic to tumor cells in vitro.", "content": "Carbamylcholine, acting via a pharmacologically specific receptor, had the ability to activate effector populations of spleen cells from female BALB/cfC3H and BALB/c mice; those cell populations were then significantly reactive in vitro against syngeneic tumor target cells but were only minimally reactive to normal syngeneic target tissues. The induced reactivity was inhibited by the muscarinic cholinergic antagonists atropine, scopolamine, and isopropamide, but not by the nicotinic antagonist d-tubocurare, and it appeared to involve both T-cell and non-T-cell effectors.", "contents": "Muscarinic cholinergic activation of mouse spleen cells cytotoxic to tumor cells in vitro. Carbamylcholine, acting via a pharmacologically specific receptor, had the ability to activate effector populations of spleen cells from female BALB/cfC3H and BALB/c mice; those cell populations were then significantly reactive in vitro against syngeneic tumor target cells but were only minimally reactive to normal syngeneic target tissues. The induced reactivity was inhibited by the muscarinic cholinergic antagonists atropine, scopolamine, and isopropamide, but not by the nicotinic antagonist d-tubocurare, and it appeared to involve both T-cell and non-T-cell effectors."}
{"id": "PMID:29134", "title": "Marke's disease herpesviruses. III. Purification and characterization of Marek's disease herpesvirus B antigen.", "content": "Sera from chickens naturally infected with Marek's disease herpesvirus (MDHV) form preciptin lines with at least two immunologically distinct soluble antigens designated MDHV-A and MDHV-B. Partial purification and characterization of the glycoprotein MDHV-A antigen was previously reported. MDHV-B was found predominantly in the sonically treated extracts of infected cells, in contrast to the predominantly extracellular MDHV-A. Analysis of these extracts from [14C]glucosamine-labeled cells by immunodiffusion with chicken anti MDHV-B serum negative for MDHV-A followed by autoradiography confirmed that MDHV-B was a common antigen between MDHV and herpesvirus of turkeys and revealed that it was also a glycoprotein. Because of their glycoprotein nature, both MDHV-A and MDHV-B bound to concanavalin A affinity chromatography columns and could then be eluted by alpha-methyl-D-mannoside and recovered for further analysis. Concanavalin A affinity chromatography was an excellent technique for initial purification of MDHV-A and MDHV-B, since approximately 5- and 15- fold purification, respectively, was achieved in a single simple step. MDHV-B was resistant to trypsin under conditions where MDHV-A was sensitive, but was similar to MDHV-A in resistance to pH 2.0 and to 1.0 or 2.0 M urea and 0.05% Brij 35. Partially purified MDHV-B was analyzed by sucrose gradient sedimentation, isoelectric focusing, and gel filtration on Sephadex G-200 in the presence of 1.0 or 2.0 M urea and 0.05% Brij 35 to purify the antigen and to determine its physical and chemical properties in comparison with those already reported for MDHV-A. MDHV-B had a much lower isoelectric point in pH 4,54, a higher sedimentation coefficient of 4.4S, and a greater molecular weight of 58,250. These data indicate that MDHV-B is physically distinct from MDHV-A antigen, although the size difference is not sufficient to allow for effective separation. In contrast, the isoelectric point difference of greater than 2 pH units makes isoelectric focusing an effective means of purifying the antigens free of one another. The four-step purification procedure achieved greater than 200-fold purification of MDHV-B. Immunization of rabbits with this highly purified antigen results in the preparation of antisera that appeared monospecific for MDHV-B in immunodiffusion.", "contents": "Marke's disease herpesviruses. III. Purification and characterization of Marek's disease herpesvirus B antigen. Sera from chickens naturally infected with Marek's disease herpesvirus (MDHV) form preciptin lines with at least two immunologically distinct soluble antigens designated MDHV-A and MDHV-B. Partial purification and characterization of the glycoprotein MDHV-A antigen was previously reported. MDHV-B was found predominantly in the sonically treated extracts of infected cells, in contrast to the predominantly extracellular MDHV-A. Analysis of these extracts from [14C]glucosamine-labeled cells by immunodiffusion with chicken anti MDHV-B serum negative for MDHV-A followed by autoradiography confirmed that MDHV-B was a common antigen between MDHV and herpesvirus of turkeys and revealed that it was also a glycoprotein. Because of their glycoprotein nature, both MDHV-A and MDHV-B bound to concanavalin A affinity chromatography columns and could then be eluted by alpha-methyl-D-mannoside and recovered for further analysis. Concanavalin A affinity chromatography was an excellent technique for initial purification of MDHV-A and MDHV-B, since approximately 5- and 15- fold purification, respectively, was achieved in a single simple step. MDHV-B was resistant to trypsin under conditions where MDHV-A was sensitive, but was similar to MDHV-A in resistance to pH 2.0 and to 1.0 or 2.0 M urea and 0.05% Brij 35. Partially purified MDHV-B was analyzed by sucrose gradient sedimentation, isoelectric focusing, and gel filtration on Sephadex G-200 in the presence of 1.0 or 2.0 M urea and 0.05% Brij 35 to purify the antigen and to determine its physical and chemical properties in comparison with those already reported for MDHV-A. MDHV-B had a much lower isoelectric point in pH 4,54, a higher sedimentation coefficient of 4.4S, and a greater molecular weight of 58,250. These data indicate that MDHV-B is physically distinct from MDHV-A antigen, although the size difference is not sufficient to allow for effective separation. In contrast, the isoelectric point difference of greater than 2 pH units makes isoelectric focusing an effective means of purifying the antigens free of one another. The four-step purification procedure achieved greater than 200-fold purification of MDHV-B. Immunization of rabbits with this highly purified antigen results in the preparation of antisera that appeared monospecific for MDHV-B in immunodiffusion."}
{"id": "PMID:29135", "title": "Effects of phosphorylation and pH on the association of NS protein with vesicular stomatitis virus cores.", "content": "The proteins of vesicular stomatitis virus (VSV) were analyzed on the basis of charge as well as size in polyacrylamide gels containing urea and acetic acid. The phosphorprotein NS was resolved into two major species. The less phosphorylated NS1 species contained about 10% fewer phosphate residues than the second species, NS2. These two phosphorylated forms were compartmentalized both in the virus and in the infected cell cytoplasm. Cores from virions and the core-containing fraction of the infected cell cytoplasm contained only the NS1 form. All of the more highly phosphorylated NS2 form and some of the NS1 form were found to be free of cores, whether they were derived from virions or from the infected cell. Therefore, the degree of phosphorylation appeared to determine whether or not the NS protein became bound to VSV cores. Moreover, the amount of bound NS1 protein relative to nucleocapsids increased as the pH of the culture medium was raised from 6.6 to 7.4. Because an increased in pH increases VSV replication (Fiszman et al., J. Virol. 13:801-808, 1974; Palma and Huang, in W.S. Robinson and C.F. Fox, ed., Mechanisms of Virus Disease, ICN-UCLA Symposia, p. 87-100, 1974), the NS1 protein may either regulate overall VSV RNA synthesis or regulate the switch between transcription and replication.", "contents": "Effects of phosphorylation and pH on the association of NS protein with vesicular stomatitis virus cores. The proteins of vesicular stomatitis virus (VSV) were analyzed on the basis of charge as well as size in polyacrylamide gels containing urea and acetic acid. The phosphorprotein NS was resolved into two major species. The less phosphorylated NS1 species contained about 10% fewer phosphate residues than the second species, NS2. These two phosphorylated forms were compartmentalized both in the virus and in the infected cell cytoplasm. Cores from virions and the core-containing fraction of the infected cell cytoplasm contained only the NS1 form. All of the more highly phosphorylated NS2 form and some of the NS1 form were found to be free of cores, whether they were derived from virions or from the infected cell. Therefore, the degree of phosphorylation appeared to determine whether or not the NS protein became bound to VSV cores. Moreover, the amount of bound NS1 protein relative to nucleocapsids increased as the pH of the culture medium was raised from 6.6 to 7.4. Because an increased in pH increases VSV replication (Fiszman et al., J. Virol. 13:801-808, 1974; Palma and Huang, in W.S. Robinson and C.F. Fox, ed., Mechanisms of Virus Disease, ICN-UCLA Symposia, p. 87-100, 1974), the NS1 protein may either regulate overall VSV RNA synthesis or regulate the switch between transcription and replication."}
{"id": "PMID:29137", "title": "Methyprylon-induced bone marrow suppression in siblings. An inherited defect?", "content": "Transient bone marrow suppression in two sisters followed ingestion of the sedative-hypnotic drug methyprylon. No other pharmacologic or environmental inciting factor common to both patients was identified. The mechanisms responsible could not be defined; abnormal suppression fo granulocyte progenitors by the drug in vitro was not demonstrable. It is postulated that a pharmacogenetic interaction may have been responsible for methyprylon-related bone marrow suppression in these two siblings.", "contents": "Methyprylon-induced bone marrow suppression in siblings. An inherited defect? Transient bone marrow suppression in two sisters followed ingestion of the sedative-hypnotic drug methyprylon. No other pharmacologic or environmental inciting factor common to both patients was identified. The mechanisms responsible could not be defined; abnormal suppression fo granulocyte progenitors by the drug in vitro was not demonstrable. It is postulated that a pharmacogenetic interaction may have been responsible for methyprylon-related bone marrow suppression in these two siblings."}
{"id": "PMID:29142", "title": "Clinical evaluation of a new anticoagulant therapy in prosthetic valve replacement.", "content": "Thromboembolic complication was correlated with the methods of anticoagulant therapy used in the patients with Starr-Edwards non cloth-covered or cloth-covered ball valve. A new anticoagulant therapy combining Bucolome with Warfarin has been used for the patients who were unable to be maintained in a suitable range of thrombotest Owren with Warfarin alone. The results obtained in this new therapy showed that the incidence of thromboembolism was reduced to 0.02 per patient year or less in the patients with Starr-Edwards ball valve as well as Bj\u00f6rk-Shiley tilting disc valve.", "contents": "Clinical evaluation of a new anticoagulant therapy in prosthetic valve replacement. Thromboembolic complication was correlated with the methods of anticoagulant therapy used in the patients with Starr-Edwards non cloth-covered or cloth-covered ball valve. A new anticoagulant therapy combining Bucolome with Warfarin has been used for the patients who were unable to be maintained in a suitable range of thrombotest Owren with Warfarin alone. The results obtained in this new therapy showed that the incidence of thromboembolism was reduced to 0.02 per patient year or less in the patients with Starr-Edwards ball valve as well as Bj\u00f6rk-Shiley tilting disc valve."}
{"id": "PMID:29155", "title": "Antisecretory effect of imidazole and its derivatives in an isolated  gastric mucosa preparation and an anesthetized young chicken preparation; comparison with a histamine H2-receptor antagonist.", "content": "We invesigated the influences of imidazole on the basal and the secretagogue-stimulated gastric acid secretion in isolated bullfrog gastric mucosa preparations and in anesthetized young chickens. Imidazoles (1 x 10(-4) g/ml) readily depressed the basal acid secretion in gastric mucosa in vitro. The inhibitory effect of imidazole was diminished considerably after washing out of the drug. The maximum acid secretion elicited by tetragastrin or bethanechol was completely antagonized by imidazole (1 x 10(-4) g/ml). The stimulatory action of histamine or dibutyryl cyclic AMP was also remarkably depressed in the presence of imidazole (3 x 10(-4) g/ml). after dibenamine pretreatment (5 x 10(-5) g/ml) for 60 min, the isolated gastric mucosa preparation became refractory to tetragastrin, bethanechol and histamine, but responded to dibutyryl cyclic AMP. Imidazole protected the histamine sensitivity against dibenamine blockade in the concentration of 5 x 10(-4) g/ml. In anesthetized young chickens, imidazole (200 mg/kg, s.c.) depressed tetragastrin- and histamine-stimulated gastric acid secretion. The effects of the imidazole derivatives and several antagonists (metiamide, atropine, diphenhydramine, acetazolamide and 2,4-dinitrophenol) on acid production were compared with that of imidazole. From these results, it is concluded that imidazole has a potent antisecretory effect on the basal and the secretagogue-stimulated acid secretion.", "contents": "Antisecretory effect of imidazole and its derivatives in an isolated  gastric mucosa preparation and an anesthetized young chicken preparation; comparison with a histamine H2-receptor antagonist. We invesigated the influences of imidazole on the basal and the secretagogue-stimulated gastric acid secretion in isolated bullfrog gastric mucosa preparations and in anesthetized young chickens. Imidazoles (1 x 10(-4) g/ml) readily depressed the basal acid secretion in gastric mucosa in vitro. The inhibitory effect of imidazole was diminished considerably after washing out of the drug. The maximum acid secretion elicited by tetragastrin or bethanechol was completely antagonized by imidazole (1 x 10(-4) g/ml). The stimulatory action of histamine or dibutyryl cyclic AMP was also remarkably depressed in the presence of imidazole (3 x 10(-4) g/ml). after dibenamine pretreatment (5 x 10(-5) g/ml) for 60 min, the isolated gastric mucosa preparation became refractory to tetragastrin, bethanechol and histamine, but responded to dibutyryl cyclic AMP. Imidazole protected the histamine sensitivity against dibenamine blockade in the concentration of 5 x 10(-4) g/ml. In anesthetized young chickens, imidazole (200 mg/kg, s.c.) depressed tetragastrin- and histamine-stimulated gastric acid secretion. The effects of the imidazole derivatives and several antagonists (metiamide, atropine, diphenhydramine, acetazolamide and 2,4-dinitrophenol) on acid production were compared with that of imidazole. From these results, it is concluded that imidazole has a potent antisecretory effect on the basal and the secretagogue-stimulated acid secretion."}
{"id": "PMID:29161", "title": "Manufacture and utilization of antimony pH electrodes.", "content": "A new technique for manufacturing single-barreled and double-barreled antimony pH microelectrodes is described. The results of investigations into the accuracy of antimony as a pH sensor disclosed that the pH-voltage response is: 1) within the physiologic range, principally the result of the hydrogen ion activity of the solution in which the voltage is being developed, 2) in part, qualitatively anion-dependent, 3) modified by the presence of significant amounts of at least carbon dioxide, oxygen, and nitrogen gases, and 4) markedly offset by fluctuations in temperature. Our results further indicate that the accuracy of antimony as a pH sensor is determined by the quality of the calibration procedure. We conclude that if the antimony electrode is to accurately determine the pH of a biological fluid, the pH calibration solutions must closely resemble the unknown biological fluid with respect to temperature, PO2, PN2, and types of buffering anions. A calibration procedure is described which can minimize errors with antimony pH estimations when measuring the pH of proximal tubular fluid of the mammalian kidney.", "contents": "Manufacture and utilization of antimony pH electrodes. A new technique for manufacturing single-barreled and double-barreled antimony pH microelectrodes is described. The results of investigations into the accuracy of antimony as a pH sensor disclosed that the pH-voltage response is: 1) within the physiologic range, principally the result of the hydrogen ion activity of the solution in which the voltage is being developed, 2) in part, qualitatively anion-dependent, 3) modified by the presence of significant amounts of at least carbon dioxide, oxygen, and nitrogen gases, and 4) markedly offset by fluctuations in temperature. Our results further indicate that the accuracy of antimony as a pH sensor is determined by the quality of the calibration procedure. We conclude that if the antimony electrode is to accurately determine the pH of a biological fluid, the pH calibration solutions must closely resemble the unknown biological fluid with respect to temperature, PO2, PN2, and types of buffering anions. A calibration procedure is described which can minimize errors with antimony pH estimations when measuring the pH of proximal tubular fluid of the mammalian kidney."}
{"id": "PMID:29168", "title": "Primary malignant melanoma of the small intestine and the APUD cell concept.", "content": "A primary melanoma of the small intestine is reported. A possible explanation of its origin according to the APUD cell concept is suggested. This concept may lessen the doubts and confusion whenever an intestinal melanoma is discovered and a primary tumor at one of the more common sites can reasonably be excluded.", "contents": "Primary malignant melanoma of the small intestine and the APUD cell concept. A primary melanoma of the small intestine is reported. A possible explanation of its origin according to the APUD cell concept is suggested. This concept may lessen the doubts and confusion whenever an intestinal melanoma is discovered and a primary tumor at one of the more common sites can reasonably be excluded."}
{"id": "PMID:29170", "title": "Age-associated changes in glutamine synthetase activity in WI-38 cells.", "content": "The human fibroblast cell line WI-38 shows a gradual decline in glutamine synthetase specific activity with increasing age in culture. However, the level of functional enzyme per cell does not change with age. Heat inactivation profiles indicate that glutamine synthetase from younger cell cultures is more heat labile than that from older cultures. A possible explanation for these observations is that alterations in the glutamine synthetase molecule occur with increasing age of WI-38 cells in culture.", "contents": "Age-associated changes in glutamine synthetase activity in WI-38 cells. The human fibroblast cell line WI-38 shows a gradual decline in glutamine synthetase specific activity with increasing age in culture. However, the level of functional enzyme per cell does not change with age. Heat inactivation profiles indicate that glutamine synthetase from younger cell cultures is more heat labile than that from older cultures. A possible explanation for these observations is that alterations in the glutamine synthetase molecule occur with increasing age of WI-38 cells in culture."}
{"id": "PMID:29171", "title": "Developmental restrictions on hormone modulated gene transcription. II. Hormone induced interactions of RNA polymerase with chromatin.", "content": "Chromatin-bound and soluble RNA polymerase subspecies have been isolated and fractionated by isoelectric focusing at various times (0, 6, 12 and 18 h) following auxin treatment of 4 day (responsive) and 8 day (unresponsive) soybean hypocotyls. Young 4 day seedlings displayed two well defined phases of auxin induced gene transcription. Phase I (6 h) evidenced the selective dissociation of many RNA polymerase subspecies from the chromatin complex which was accompanied by the retention of three class II enzymes. Phase II occurred after 12 h of treatment when the dissociated enzymes including some species which were soluble in the 0 h controls became re-associated with chromatin. These induced RNA polymerases may be responsible for the synthesis of auxin induced RNAs. In contrast, the unresponsive 8 day hypocotyl did not display two phases of auxin induction. Phase one, the dissociation of the chromatin bound enzymes, occurred at 12 h (compared to 6 h for the 4 day seedling) and was not followed by the later translocation of any soluble enzymes towards the chromatin complex. The results support earlier findings suggesting that the developmental \"phasing out\" of RNA polymerase subspecies limits the hormone induced growth response of this tissue and thus is regarded as an off switch for the transcription of such hormone controlled gene sequences.", "contents": "Developmental restrictions on hormone modulated gene transcription. II. Hormone induced interactions of RNA polymerase with chromatin. Chromatin-bound and soluble RNA polymerase subspecies have been isolated and fractionated by isoelectric focusing at various times (0, 6, 12 and 18 h) following auxin treatment of 4 day (responsive) and 8 day (unresponsive) soybean hypocotyls. Young 4 day seedlings displayed two well defined phases of auxin induced gene transcription. Phase I (6 h) evidenced the selective dissociation of many RNA polymerase subspecies from the chromatin complex which was accompanied by the retention of three class II enzymes. Phase II occurred after 12 h of treatment when the dissociated enzymes including some species which were soluble in the 0 h controls became re-associated with chromatin. These induced RNA polymerases may be responsible for the synthesis of auxin induced RNAs. In contrast, the unresponsive 8 day hypocotyl did not display two phases of auxin induction. Phase one, the dissociation of the chromatin bound enzymes, occurred at 12 h (compared to 6 h for the 4 day seedling) and was not followed by the later translocation of any soluble enzymes towards the chromatin complex. The results support earlier findings suggesting that the developmental \"phasing out\" of RNA polymerase subspecies limits the hormone induced growth response of this tissue and thus is regarded as an off switch for the transcription of such hormone controlled gene sequences."}
{"id": "PMID:29219", "title": "Emergence of multiply resistant pneumococci.", "content": "Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.", "contents": "Emergence of multiply resistant pneumococci. Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration."}
{"id": "PMID:29225", "title": "Polygalacturonase, biomass and ascospore production by Byssochlamys fulva. II. Effects of sugars found in fruits.", "content": "Polygalacturonase, biomass, and ascospore production by four strains of Byssochlamys fulva cultured in laboratory media supplemented with glucose, sucrose, or fructose was studied over a 20-day incubation period at 30 degrees C. The production of polygalacturonase was variable, but most activity was detected between 4 and 8 days in 1% sugar media at an initial pH of 4 or 5. The rate of biomass production was retarded early in the incubation period in media initially at pH 3 or 4 as compared to pH 5, but the amount of growth was about the same in media containing the test sugars after 20 days. Large numbers of ascospores were produced between 8 and 10 days in media containing 5% sugar initially at pH 5 and 4. Production of ascospores was retarded at pH 3 in media containing 5% sugar as compared to media initially at pH 5 and 4.", "contents": "Polygalacturonase, biomass and ascospore production by Byssochlamys fulva. II. Effects of sugars found in fruits. Polygalacturonase, biomass, and ascospore production by four strains of Byssochlamys fulva cultured in laboratory media supplemented with glucose, sucrose, or fructose was studied over a 20-day incubation period at 30 degrees C. The production of polygalacturonase was variable, but most activity was detected between 4 and 8 days in 1% sugar media at an initial pH of 4 or 5. The rate of biomass production was retarded early in the incubation period in media initially at pH 3 or 4 as compared to pH 5, but the amount of growth was about the same in media containing the test sugars after 20 days. Large numbers of ascospores were produced between 8 and 10 days in media containing 5% sugar initially at pH 5 and 4. Production of ascospores was retarded at pH 3 in media containing 5% sugar as compared to media initially at pH 5 and 4."}
{"id": "PMID:29226", "title": "The distribution of geophilic dermatophytes in Kenyan soils.", "content": "Two hundred and eighty one soil samples from different provinces of Kenya were examined for dermatophytes by the hair baiting technique. Dermatophytes were recovered from 84 samples. Microsporum gypseum constituted 75.8% of the total isolates while Keratinomyces ajelloi and M. cookei formed 21% and 3.2%, respectively. The distribution of the dermatophytes was influences by soil pH, being more prevalent in acidic than in alkaline soils.", "contents": "The distribution of geophilic dermatophytes in Kenyan soils. Two hundred and eighty one soil samples from different provinces of Kenya were examined for dermatophytes by the hair baiting technique. Dermatophytes were recovered from 84 samples. Microsporum gypseum constituted 75.8% of the total isolates while Keratinomyces ajelloi and M. cookei formed 21% and 3.2%, respectively. The distribution of the dermatophytes was influences by soil pH, being more prevalent in acidic than in alkaline soils."}
{"id": "PMID:29227", "title": "Mycological profile of crew during 56-day simulated orbital flight.", "content": "Mycological analyses were made on specimens obtained from the skin, oral rinse, urine, and feces of three subjects participating in a 56 day Skylab simulation test. Samples were taken over a 175 day period divided into three phases consisting of a prechamber, intrachamber, and postchamber period. A total of 69 species of filamentous fungi and 22 species of yeast and yeast-like fungi were recovered and identified. There was a marked decrease in the isolation incidence of both the filamentous and yeast and yeast-like fungi during the intrachamber period. This, taken with the fact that 71% of the filamentous species and 55% of the yeast and yeast-like species were isolated no more than twice, reflects the transitory nature of the relationship between the human body and most fungi. However, there was a relative increase in the potential pathogens Candida albicans and Candida parapsilosis during the intrachamber period. Over 50% of all fungi recovered were isolated from the nasal and oral cavities. There was no evidence of intercrew transfer of a particular species during the intrachamber period nor was there any evidence of microbial shock during the postchamber period.", "contents": "Mycological profile of crew during 56-day simulated orbital flight. Mycological analyses were made on specimens obtained from the skin, oral rinse, urine, and feces of three subjects participating in a 56 day Skylab simulation test. Samples were taken over a 175 day period divided into three phases consisting of a prechamber, intrachamber, and postchamber period. A total of 69 species of filamentous fungi and 22 species of yeast and yeast-like fungi were recovered and identified. There was a marked decrease in the isolation incidence of both the filamentous and yeast and yeast-like fungi during the intrachamber period. This, taken with the fact that 71% of the filamentous species and 55% of the yeast and yeast-like species were isolated no more than twice, reflects the transitory nature of the relationship between the human body and most fungi. However, there was a relative increase in the potential pathogens Candida albicans and Candida parapsilosis during the intrachamber period. Over 50% of all fungi recovered were isolated from the nasal and oral cavities. There was no evidence of intercrew transfer of a particular species during the intrachamber period nor was there any evidence of microbial shock during the postchamber period."}
{"id": "PMID:29245", "title": "Experiments to increase the selectivity of tumor chemotherapy by means of in vivo activation of transport forms of cancerostatics by exogenous enzymes.", "content": "A significant tumor damaging effect (growth inhibition) on transplanted syngeneic sarcoma in mouse was obtained by means of pH-dependent activation of a transport form of a cancerostatic drug by an enzyme foreign to the organism. This effect was achieved by combined administration of 8-0-(alpha-L-arabinofuranosyl)beta-peltatin-A as a transport form of beta-peltatin-A and the exogenous enzyme alpha-L-arabinofuranosidase from Aspergillus niger and additional increase of the acidity of the tumor by injection of glucose. The combined application of the transport form plus enzyme showed a more favorable effect on selectivity than free peltatin when a quantitative comparison was made between the tumor growth inhibition and the damage to the blood picture.", "contents": "Experiments to increase the selectivity of tumor chemotherapy by means of in vivo activation of transport forms of cancerostatics by exogenous enzymes. A significant tumor damaging effect (growth inhibition) on transplanted syngeneic sarcoma in mouse was obtained by means of pH-dependent activation of a transport form of a cancerostatic drug by an enzyme foreign to the organism. This effect was achieved by combined administration of 8-0-(alpha-L-arabinofuranosyl)beta-peltatin-A as a transport form of beta-peltatin-A and the exogenous enzyme alpha-L-arabinofuranosidase from Aspergillus niger and additional increase of the acidity of the tumor by injection of glucose. The combined application of the transport form plus enzyme showed a more favorable effect on selectivity than free peltatin when a quantitative comparison was made between the tumor growth inhibition and the damage to the blood picture."}
{"id": "PMID:29246", "title": "[Neuroleptics with prolonged action].", "content": "In the last twenty years, the study of long-acting neuroleptic drugs has been active and promising progress in maintenance of psychotic patients. At present, there are several long-acting derivatives of phenothiazines, e.g. thioridazine, or drugs that allow the esterification of phenothiazine, e.g. perphenazine, fluphenazine and pipothiazine. Other esterifiable product is flupenthizol, which is a thioxanthene, and other long-acting drug is chlofluperol, which is a butyrophenone derivative. There is also a new series of neuroleptics, diphenilbultilpiperidine derivatives, such as fluspirilene, pimocide and penfluridol. Our clinical studies with these drugs allows us to state that there is a new revolution in pharmacological psychiatry, with important perspectives in the ways of helping patients.", "contents": "[Neuroleptics with prolonged action]. In the last twenty years, the study of long-acting neuroleptic drugs has been active and promising progress in maintenance of psychotic patients. At present, there are several long-acting derivatives of phenothiazines, e.g. thioridazine, or drugs that allow the esterification of phenothiazine, e.g. perphenazine, fluphenazine and pipothiazine. Other esterifiable product is flupenthizol, which is a thioxanthene, and other long-acting drug is chlofluperol, which is a butyrophenone derivative. There is also a new series of neuroleptics, diphenilbultilpiperidine derivatives, such as fluspirilene, pimocide and penfluridol. Our clinical studies with these drugs allows us to state that there is a new revolution in pharmacological psychiatry, with important perspectives in the ways of helping patients."}
{"id": "PMID:29249", "title": "[Treatment of epileptic crisis with chlorazepate dipotassium. Clinical study of 48 patients with the determination of serum levels of nordiazepam].", "content": "48 patients with several types of seizures (following the international classification of epileptic seizures), were studied. Dipotassium chlorazepate was administered as a secondary antiepileptic drug. The cases were selected due to the severity of their seizures. The therapeutic results were evaluated with a daily record of seizures and attempt was made to correlate the serum levels of nordiazepam with the clinical results.", "contents": "[Treatment of epileptic crisis with chlorazepate dipotassium. Clinical study of 48 patients with the determination of serum levels of nordiazepam]. 48 patients with several types of seizures (following the international classification of epileptic seizures), were studied. Dipotassium chlorazepate was administered as a secondary antiepileptic drug. The cases were selected due to the severity of their seizures. The therapeutic results were evaluated with a daily record of seizures and attempt was made to correlate the serum levels of nordiazepam with the clinical results."}
{"id": "PMID:29261", "title": "[Study of the antispastic activity of prifinium bromide in motor dysfunction of the esophagus].", "content": "Motor disturbances of the oesophagus are attributable to hypermotility or hypomotility, or to peristaltic uncoordination of the upper or lower sphincter, or of the corpus. Endoesophageal manometry has enabled considerable progress to be made in the study of oesophageal dysfunction by allowing the spasm to be quantified. Treatment is poorly effective and its results are uncertain, save in the very few cases where surgery leads to resolution. For this reason, the efficacy of a new drug with marked antispastic properties, prifinium bromide, was investigated in 12 cases of megaoesophagus, of hiatal hernia, 6 of diverticulum, and 4 of dyskinesia in the light of the manometric values observed before and after its administration. The drug relieved spasm of the sphincters and corpus.", "contents": "[Study of the antispastic activity of prifinium bromide in motor dysfunction of the esophagus]. Motor disturbances of the oesophagus are attributable to hypermotility or hypomotility, or to peristaltic uncoordination of the upper or lower sphincter, or of the corpus. Endoesophageal manometry has enabled considerable progress to be made in the study of oesophageal dysfunction by allowing the spasm to be quantified. Treatment is poorly effective and its results are uncertain, save in the very few cases where surgery leads to resolution. For this reason, the efficacy of a new drug with marked antispastic properties, prifinium bromide, was investigated in 12 cases of megaoesophagus, of hiatal hernia, 6 of diverticulum, and 4 of dyskinesia in the light of the manometric values observed before and after its administration. The drug relieved spasm of the sphincters and corpus."}
{"id": "PMID:29265", "title": "[Effect of mouse age on the ability of hematopoietic stem cells to interact with thymus cells].", "content": "The effect of the thymus cells of the C57BL/6 mice on the colony forming ability of the stem hemopoietic cells of the embryonic liver and bone marrow of young (3 months) and old (2 years) mice was studied their joint transplantation into the mice (CBAXXC57BL/6) F1. The stimulating effect of the thymus cells on the colony forming ability of the stem hemopoietic cells of different age depends both on the dose of the stem hemopoietic cells of embryonic liver and the dose of T-lymphocytes. A suggestion is put forward that the stimulating effect of the thymus cells on the colony formation is due to their interaction with the stem cells in the G2 phase of the mitotic cycle.", "contents": "[Effect of mouse age on the ability of hematopoietic stem cells to interact with thymus cells]. The effect of the thymus cells of the C57BL/6 mice on the colony forming ability of the stem hemopoietic cells of the embryonic liver and bone marrow of young (3 months) and old (2 years) mice was studied their joint transplantation into the mice (CBAXXC57BL/6) F1. The stimulating effect of the thymus cells on the colony forming ability of the stem hemopoietic cells of different age depends both on the dose of the stem hemopoietic cells of embryonic liver and the dose of T-lymphocytes. A suggestion is put forward that the stimulating effect of the thymus cells on the colony formation is due to their interaction with the stem cells in the G2 phase of the mitotic cycle."}
{"id": "PMID:29266", "title": "[Relationship between hematopoietic stem differentiation and the functional state of the thymus].", "content": "The direction of differentiation of the stem cells with respect to the physiological activity of thymus determined by the age of an animal was studied by means of histological analysis of hemopoietic colonies in the spleen of lethally irradiated mice. The immaturity of thymus of its involution are characterized by the inhibition of differentiation of the stem cell along the granuloid path. An analysis of the data on differentiation of the stem cells in mice of different age, as well as in thymectomized mice allows to draw a conclusion that the process of differentiation of the hemopoietic stem cells is thymus-dependent.", "contents": "[Relationship between hematopoietic stem differentiation and the functional state of the thymus]. The direction of differentiation of the stem cells with respect to the physiological activity of thymus determined by the age of an animal was studied by means of histological analysis of hemopoietic colonies in the spleen of lethally irradiated mice. The immaturity of thymus of its involution are characterized by the inhibition of differentiation of the stem cell along the granuloid path. An analysis of the data on differentiation of the stem cells in mice of different age, as well as in thymectomized mice allows to draw a conclusion that the process of differentiation of the hemopoietic stem cells is thymus-dependent."}
{"id": "PMID:29274", "title": "Takayasu arteritis and renovascular hypertension in childhood.", "content": "Takayasu arteritis with renal artery involvement was the cause of severe persistent hypertension in eight children under 12 years of age. Features of severe hypertension dominated the clinical picture. Unequal or absent pulses were found in three patients. An irregular contour of the descending thoracic aorta on the chest roentgenogram was an early clue to the diagnosis. On aortography both renal arteries were affected in five patients, although a discrepancy in kidney size on excretory urography had suggested a unilateral lesion. Total aortography is mandatory to outline the full extent of the vascular abnormalities. All the patients had strongly positive tuberculin skin tests, and, although mycobacteria were not isolated, all patients received antituberculous as well as antihypertensive therapy. Nephrectomy of the worse kidney is contraindicated if the renal arteries are asymmetrically involved, for fear of later extension of the arteritis. Takayasu arteritis is an important cause of severe persistent hypertension in nonwhite children.", "contents": "Takayasu arteritis and renovascular hypertension in childhood. Takayasu arteritis with renal artery involvement was the cause of severe persistent hypertension in eight children under 12 years of age. Features of severe hypertension dominated the clinical picture. Unequal or absent pulses were found in three patients. An irregular contour of the descending thoracic aorta on the chest roentgenogram was an early clue to the diagnosis. On aortography both renal arteries were affected in five patients, although a discrepancy in kidney size on excretory urography had suggested a unilateral lesion. Total aortography is mandatory to outline the full extent of the vascular abnormalities. All the patients had strongly positive tuberculin skin tests, and, although mycobacteria were not isolated, all patients received antituberculous as well as antihypertensive therapy. Nephrectomy of the worse kidney is contraindicated if the renal arteries are asymmetrically involved, for fear of later extension of the arteritis. Takayasu arteritis is an important cause of severe persistent hypertension in nonwhite children."}
{"id": "PMID:29277", "title": "The response of lymphatic smooth muscles to vasoactive substances.", "content": "A study was made of the isotonic response of bovine mesenteric lymphatics to several physiological vasoactive substances. Contractions of lymphatic smooth muscles were induced by serotonin (5-HT), prostaglandin F2alpha (PGF2alpha), noradrenaline (NA), histamine, dopamine and acetylcholine (ACh). The smooth muscles were particularly sensitive to 5-HT. Excepting PGF2alpha no other substances could equal 5-HT in the magnitude of the maximum response. The majority of 5-HT receptors seemed to be the D receptors. The decreasing order of the contractile responses was as follows: 5-HT greater than PGF2alpha greater than NA greater than histamine greater than dopamine greater than ACh. The contractile response to ACh was observed only in specimens involving valvular region. It was very likely that, in the lymphatics, there were 2 kinds of receptors for catecholamines, i.e. alpha and beta receptors, and the stimulation of the former induced smooth muscle contraction and that of the latter relaxation. A difference was noticed between the responses of valvular and intervalvular segments to NA. Relaxations of lymphatic smooth muscles were induced not only by isoproterenol but also by adenosine and adenine nucleotides. The decreasing order of the relaxant responses was as follows: ISP greater than adenosine greater than ATP greater than ADP greater cyclic AMP greater than or equal to AMP. The relaxant responses to adenine nucleotides tended to reduce with decrease in the number of high energy phosphates.", "contents": "The response of lymphatic smooth muscles to vasoactive substances. A study was made of the isotonic response of bovine mesenteric lymphatics to several physiological vasoactive substances. Contractions of lymphatic smooth muscles were induced by serotonin (5-HT), prostaglandin F2alpha (PGF2alpha), noradrenaline (NA), histamine, dopamine and acetylcholine (ACh). The smooth muscles were particularly sensitive to 5-HT. Excepting PGF2alpha no other substances could equal 5-HT in the magnitude of the maximum response. The majority of 5-HT receptors seemed to be the D receptors. The decreasing order of the contractile responses was as follows: 5-HT greater than PGF2alpha greater than NA greater than histamine greater than dopamine greater than ACh. The contractile response to ACh was observed only in specimens involving valvular region. It was very likely that, in the lymphatics, there were 2 kinds of receptors for catecholamines, i.e. alpha and beta receptors, and the stimulation of the former induced smooth muscle contraction and that of the latter relaxation. A difference was noticed between the responses of valvular and intervalvular segments to NA. Relaxations of lymphatic smooth muscles were induced not only by isoproterenol but also by adenosine and adenine nucleotides. The decreasing order of the relaxant responses was as follows: ISP greater than adenosine greater than ATP greater than ADP greater cyclic AMP greater than or equal to AMP. The relaxant responses to adenine nucleotides tended to reduce with decrease in the number of high energy phosphates."}
{"id": "PMID:29278", "title": "High pyruvate kinase activity causes low concentration of 2,3-diphosphoglycerate in fetal rabbit red cells.", "content": "1. The high oxygen affinity of fetal blood in rabbits is due to a very low concentration of 2,3-diphosphoglycerate (2,3-DPG) in the red cells. In order to gather informations on the factors responsible for this characteristic we have studied synthesis and break-down of 2,3-DPG in fetal and adult rabbit red cells in vitro and examined possible regulative pathways which may lead to the low 2,3-DPG concentration in vivo. 2. Under conditions where 2,3-DPG and 3-phosphoglycerate (3-PGA) accumulate in adult erythrocytes, i.e. in a solution containing inosine, pyruvate and inorganic phosphate, the amount of 2,3-DPG synthetized in fetal red cells was only 40% of the adult value and 3-PGA was not measurable. Upon inhibition of enolase by NaF, however, both 2,3-DPG and 3-PGA increased to a similar extent in fetal and adult red cells. These findings point towards differences in the pyruvate kinase (PK) reaction which is one of the rate limiting steps of glycolysis. Direct measurements revealed an over tenfold higher PK activity in fetal compared to adult red cells. This higher activity of PK will lead to a decreased concentration of 3-PGA with a consecutive fall in 2,3-DPG concentration. 3. Other factors, like a decreased glucose utilization, a decreased activity of 2,3-DPG mutase or an increased 2,3-DPG phosphatase activity could be excluded as a cause for the low 2,3-DPG concentration in fetal red blood cells. The same holds for extraerythrocytic factors like glucose concentration or pH value in fetal blood. 4. During the postnatal development of rabbits the PK activity decreased. 50 days after birth, PK activity was 20% of the fetal value but still somewhat higher than in adult erythrocytes. This change is paralleled by an increase in 2,3-DPG concentration and half saturation oxygen pressure. With respect to the synthesis of 2,3-DPG and ATP, the fetal rabbit red cell is comparable to hereditary high PK activity in human erythrocytes.", "contents": "High pyruvate kinase activity causes low concentration of 2,3-diphosphoglycerate in fetal rabbit red cells. 1. The high oxygen affinity of fetal blood in rabbits is due to a very low concentration of 2,3-diphosphoglycerate (2,3-DPG) in the red cells. In order to gather informations on the factors responsible for this characteristic we have studied synthesis and break-down of 2,3-DPG in fetal and adult rabbit red cells in vitro and examined possible regulative pathways which may lead to the low 2,3-DPG concentration in vivo. 2. Under conditions where 2,3-DPG and 3-phosphoglycerate (3-PGA) accumulate in adult erythrocytes, i.e. in a solution containing inosine, pyruvate and inorganic phosphate, the amount of 2,3-DPG synthetized in fetal red cells was only 40% of the adult value and 3-PGA was not measurable. Upon inhibition of enolase by NaF, however, both 2,3-DPG and 3-PGA increased to a similar extent in fetal and adult red cells. These findings point towards differences in the pyruvate kinase (PK) reaction which is one of the rate limiting steps of glycolysis. Direct measurements revealed an over tenfold higher PK activity in fetal compared to adult red cells. This higher activity of PK will lead to a decreased concentration of 3-PGA with a consecutive fall in 2,3-DPG concentration. 3. Other factors, like a decreased glucose utilization, a decreased activity of 2,3-DPG mutase or an increased 2,3-DPG phosphatase activity could be excluded as a cause for the low 2,3-DPG concentration in fetal red blood cells. The same holds for extraerythrocytic factors like glucose concentration or pH value in fetal blood. 4. During the postnatal development of rabbits the PK activity decreased. 50 days after birth, PK activity was 20% of the fetal value but still somewhat higher than in adult erythrocytes. This change is paralleled by an increase in 2,3-DPG concentration and half saturation oxygen pressure. With respect to the synthesis of 2,3-DPG and ATP, the fetal rabbit red cell is comparable to hereditary high PK activity in human erythrocytes."}
{"id": "PMID:29279", "title": "Cooperation of peripheral and central chemosensitive mechanisms in the control of the extracellular pH in brain in non-respiratory acidosis.", "content": "The mathematical model of the respiratory control system in man of Middendorf and Loeschcke (1976 a, b) opens the possibility to stimulate the constellation of parameters in non-respiratory acidosis. Several investigators agree that the pH in CSF or in the extracellular fluid of the brain stays remarkably constant in this situation and it can be shown that this is a result of a precise control rather than the consequence of a sluggishly reacting system. Application of the model assuming constant extracellular brain pH allowed to calculate the relative sensitivities to pH changes of the central and the peripheral sensory mechanisms generating respiratory drive. Assuming air breathing and a normal critical arterial O2-pressure and otherwise normal parameters of respiration, circulation and blood composition (except diminished buffer base) the central chemosensitivity to a pH change turned out to be 25 times the peripheral. This factor is critically dependent on the ratio of the bicarbonate change in extracellular brain fluid to that in arterial blood. The coinciding data of Fencl (1971) and of Kronenberg and Cain (1968) were used for the calculation.", "contents": "Cooperation of peripheral and central chemosensitive mechanisms in the control of the extracellular pH in brain in non-respiratory acidosis. The mathematical model of the respiratory control system in man of Middendorf and Loeschcke (1976 a, b) opens the possibility to stimulate the constellation of parameters in non-respiratory acidosis. Several investigators agree that the pH in CSF or in the extracellular fluid of the brain stays remarkably constant in this situation and it can be shown that this is a result of a precise control rather than the consequence of a sluggishly reacting system. Application of the model assuming constant extracellular brain pH allowed to calculate the relative sensitivities to pH changes of the central and the peripheral sensory mechanisms generating respiratory drive. Assuming air breathing and a normal critical arterial O2-pressure and otherwise normal parameters of respiration, circulation and blood composition (except diminished buffer base) the central chemosensitivity to a pH change turned out to be 25 times the peripheral. This factor is critically dependent on the ratio of the bicarbonate change in extracellular brain fluid to that in arterial blood. The coinciding data of Fencl (1971) and of Kronenberg and Cain (1968) were used for the calculation."}
{"id": "PMID:29281", "title": "Purification and properties of DNA-dependent DNA-polymerases from Neurospora crassa.", "content": "Two DNA-dependent DNA-polymerases (E.C. 2.7.7.7) are partially purified from the high speed supernatant of mechanically disrupted hyphae of Neurospora crassa WT 74A. Some properties such as temperature and pH optimum and theoptimal concentrations for Mg2+, Zn2+, NH4+ and Na+ are very similar. On the other hand these enzymes show different properties on ion-exchange columns, are well distinguished by molecular weight (147 000 d and 110 000 d for A and B resp.) and the stimulation by K+ differs (K+ optimum for A: 5-70 mM and for B: 45 mM). Mn2+ and Zn2+ inhibit incorporation of deoxyribonucleoside monophosphates between 70 and 90%. Our best preparations so far have specific activities of 13 200 units/mg protein for A and 12 000 units/mg protein for B.", "contents": "Purification and properties of DNA-dependent DNA-polymerases from Neurospora crassa. Two DNA-dependent DNA-polymerases (E.C. 2.7.7.7) are partially purified from the high speed supernatant of mechanically disrupted hyphae of Neurospora crassa WT 74A. Some properties such as temperature and pH optimum and theoptimal concentrations for Mg2+, Zn2+, NH4+ and Na+ are very similar. On the other hand these enzymes show different properties on ion-exchange columns, are well distinguished by molecular weight (147 000 d and 110 000 d for A and B resp.) and the stimulation by K+ differs (K+ optimum for A: 5-70 mM and for B: 45 mM). Mn2+ and Zn2+ inhibit incorporation of deoxyribonucleoside monophosphates between 70 and 90%. Our best preparations so far have specific activities of 13 200 units/mg protein for A and 12 000 units/mg protein for B."}
{"id": "PMID:29290", "title": "Observations on vascular neuropathies.", "content": "A series of autopsy studies is presented of 13 cases of obliterative vascular disease of the vasa nervorum in a wide range of conditions, including polyarteritis nodosa, Wegener's granulomatosis, lymphomatoid granulomatosis, polymyositis and rheumatoid arthritis. In most cases, including 1 of rheumatoid neuropathy, the lesions were of the necrotising type. This supports the concept of polyarteritis nodosa as a pattern of reaction common to several diseases rather than that of a specific nosological entity. The remaining 4 cases of rheumatoid neuropathy, were associated with a bland endarteritis known as Bywater's arteritis. A comparison of these autopsy findings with clinical data and observations on sural nerve biopsies leads to the conclusion that all severe and most of the mild cases of rheumatoid neuropathy are due to occlusive vascular disease. Segmental demyelination independent of vascular lesions may be responsible for some of the mild cases and is frequently found in patients without clinical neurological manifestations.", "contents": "Observations on vascular neuropathies. A series of autopsy studies is presented of 13 cases of obliterative vascular disease of the vasa nervorum in a wide range of conditions, including polyarteritis nodosa, Wegener's granulomatosis, lymphomatoid granulomatosis, polymyositis and rheumatoid arthritis. In most cases, including 1 of rheumatoid neuropathy, the lesions were of the necrotising type. This supports the concept of polyarteritis nodosa as a pattern of reaction common to several diseases rather than that of a specific nosological entity. The remaining 4 cases of rheumatoid neuropathy, were associated with a bland endarteritis known as Bywater's arteritis. A comparison of these autopsy findings with clinical data and observations on sural nerve biopsies leads to the conclusion that all severe and most of the mild cases of rheumatoid neuropathy are due to occlusive vascular disease. Segmental demyelination independent of vascular lesions may be responsible for some of the mild cases and is frequently found in patients without clinical neurological manifestations."}
{"id": "PMID:29291", "title": "Correlation of the biological activity and solution conformation of [Asp1,Ile5]- and [Phe4,Tyr8]angiotensin II.", "content": "Angiotensin II is known to undergo a reversible conformational transition and a change in potency in rat uterus in vitro with pK approximately 6.5. We have shown by carbon-13 NMR that the conformational transition involves all-trans to partly cis isomerization of the His6-Pro7 peptide bond. Isomerization from all-trans at pH 6.8 to approximately 16% cis at pH 8.0 is therefore correlated with a 10-fold increase in biological activity for [Asp1,Ile5]-angiotensin II in rat uterus in vitro. Isomerization from all-trans at pH 6.8 to approximately 16% cis at pH 8.0 in the competitive inhibitor [Phe4,Tyr8]angiotensin II is correlated with exhibition of virtually no agonist activity at low pH to full agonist activity at high pH. An angiotensin II conformation with Pro7 in the cis form may therefore be the conformation with maximal binding or biological activity at the cellular receptor.", "contents": "Correlation of the biological activity and solution conformation of [Asp1,Ile5]- and [Phe4,Tyr8]angiotensin II. Angiotensin II is known to undergo a reversible conformational transition and a change in potency in rat uterus in vitro with pK approximately 6.5. We have shown by carbon-13 NMR that the conformational transition involves all-trans to partly cis isomerization of the His6-Pro7 peptide bond. Isomerization from all-trans at pH 6.8 to approximately 16% cis at pH 8.0 is therefore correlated with a 10-fold increase in biological activity for [Asp1,Ile5]-angiotensin II in rat uterus in vitro. Isomerization from all-trans at pH 6.8 to approximately 16% cis at pH 8.0 in the competitive inhibitor [Phe4,Tyr8]angiotensin II is correlated with exhibition of virtually no agonist activity at low pH to full agonist activity at high pH. An angiotensin II conformation with Pro7 in the cis form may therefore be the conformation with maximal binding or biological activity at the cellular receptor."}
{"id": "PMID:29292", "title": "Role of a transmembrane pH gradient in epinephrine transport by chromaffin granule membrane vesicles.", "content": "ATP-driven transport and accumulation of epinephrine in chromaffin granule membrane vesicles isolated from bovine adrenal medulla is inhibited by the proton ionophores carbonylcyanide p-trifluoromethoxyphenylhydrazone and nigericin, but not by valinomycin. Moreover, an artificially imposed pH gradient (interior acid) is able to drive this reserpine-sensitive transport system in the absence of ATP. Dicyclohexylcarbodiimide, an inactivator of the chromaffin granule membrane-bound ATPase, completely inhibits ATP-dependent epinephrine accumulation, but has much less effect when an imposed pH gradient is the driving force for epinephrine transport. The findings provide a strong indication that a pH gradient (interior acid) is the immediate driving force for epinephrine uptake in these storage granules and suggest that ATP-driven epinephrine transport is the result of two processes: (i) generation of a proton electrochemical gradient (interior acid and positive) by the membrane-bound, proton-translocating ATPase; and (ii) pH gradient-driven accumulation of the catecholamine.", "contents": "Role of a transmembrane pH gradient in epinephrine transport by chromaffin granule membrane vesicles. ATP-driven transport and accumulation of epinephrine in chromaffin granule membrane vesicles isolated from bovine adrenal medulla is inhibited by the proton ionophores carbonylcyanide p-trifluoromethoxyphenylhydrazone and nigericin, but not by valinomycin. Moreover, an artificially imposed pH gradient (interior acid) is able to drive this reserpine-sensitive transport system in the absence of ATP. Dicyclohexylcarbodiimide, an inactivator of the chromaffin granule membrane-bound ATPase, completely inhibits ATP-dependent epinephrine accumulation, but has much less effect when an imposed pH gradient is the driving force for epinephrine transport. The findings provide a strong indication that a pH gradient (interior acid) is the immediate driving force for epinephrine uptake in these storage granules and suggest that ATP-driven epinephrine transport is the result of two processes: (i) generation of a proton electrochemical gradient (interior acid and positive) by the membrane-bound, proton-translocating ATPase; and (ii) pH gradient-driven accumulation of the catecholamine."}
{"id": "PMID:29293", "title": "Gaucher disease: isolation and comparison of normal and mutant glucocerebrosidase from human spleen tissue.", "content": "Glucocerebrosidase was purified 26,000-fold from spleens from normal humans and from patients with Gaucher disease (Gaucher spleens). The specific activities of the purified normal and mutant enzymes with glucocerebroside as substrate were 8.5 X 10(5) and 5.4 X 10(4) nmol/mg of protein per hr, respectively. The ratio of enzymatic activities was constant throughout the isolation procedure. The two enzymes appeared to be similar by other parameters such as substrate affinity, heat lability, and pH optimum. Immunotitration with glucocerebrosidase antiserum showed equivalent quantities of crossreacting material in extracts of normal and Gaucher spleens. These data strongly suggest that the genetic basis of Gaucher disease is a strucutral mutation of glucocerebrosidase. The results of sodium dodecyl sulfate gel electrophporesis also indicate that there are differences between the normal and the Gaucher disease enzyme.", "contents": "Gaucher disease: isolation and comparison of normal and mutant glucocerebrosidase from human spleen tissue. Glucocerebrosidase was purified 26,000-fold from spleens from normal humans and from patients with Gaucher disease (Gaucher spleens). The specific activities of the purified normal and mutant enzymes with glucocerebroside as substrate were 8.5 X 10(5) and 5.4 X 10(4) nmol/mg of protein per hr, respectively. The ratio of enzymatic activities was constant throughout the isolation procedure. The two enzymes appeared to be similar by other parameters such as substrate affinity, heat lability, and pH optimum. Immunotitration with glucocerebrosidase antiserum showed equivalent quantities of crossreacting material in extracts of normal and Gaucher spleens. These data strongly suggest that the genetic basis of Gaucher disease is a strucutral mutation of glucocerebrosidase. The results of sodium dodecyl sulfate gel electrophporesis also indicate that there are differences between the normal and the Gaucher disease enzyme."}
{"id": "PMID:29313", "title": "Potentiation by neuroleptic agents of the inhibitory action of intraperitoneally administered GABA on the locomotor activity of mice.", "content": "The ability of several neuroleptics to potentiate the inhibitory action of IP administered GABA on the motor activity of mice has been investigated. Haloperidol, chlorpromazine, thioridazine, and clozapine, but not the apparently selective dopamine receptor-blocking agent spiperone, were found to possess such activity. Phenoxybenzamine also proved active in potentiating GABA. Thus blockade of dopamine receptors as well as alpha-adrenergic receptors may be responsible for neuroleptic-induced potentiation of GABA actions.", "contents": "Potentiation by neuroleptic agents of the inhibitory action of intraperitoneally administered GABA on the locomotor activity of mice. The ability of several neuroleptics to potentiate the inhibitory action of IP administered GABA on the motor activity of mice has been investigated. Haloperidol, chlorpromazine, thioridazine, and clozapine, but not the apparently selective dopamine receptor-blocking agent spiperone, were found to possess such activity. Phenoxybenzamine also proved active in potentiating GABA. Thus blockade of dopamine receptors as well as alpha-adrenergic receptors may be responsible for neuroleptic-induced potentiation of GABA actions."}
{"id": "PMID:29315", "title": "A new putative neuroregulator of the extrapyramidal system.", "content": "A putative neurotransmitter, 2-phenylethylamine, which is most highly concentrated in the extrapyramidal system of human brain, is able to reverse reserpine-induced parkinsonism in animals and elicit stereotypy. This action is only partially antagonized after catecholamine depletion by pretreatment with a-methyl-para-tyrosine, and fully blocked by pretreatment with haloperidol, a dopamine receptor blocker. Therefore, via direct and/or indirect actions, 2-phenylethylamine may serve a neuroregulatory role in the extrapyramidal system.", "contents": "A new putative neuroregulator of the extrapyramidal system. A putative neurotransmitter, 2-phenylethylamine, which is most highly concentrated in the extrapyramidal system of human brain, is able to reverse reserpine-induced parkinsonism in animals and elicit stereotypy. This action is only partially antagonized after catecholamine depletion by pretreatment with a-methyl-para-tyrosine, and fully blocked by pretreatment with haloperidol, a dopamine receptor blocker. Therefore, via direct and/or indirect actions, 2-phenylethylamine may serve a neuroregulatory role in the extrapyramidal system."}
{"id": "PMID:29316", "title": "The isolated nictitating membrane of the cat. A new model for the study of narcotic analgesics.", "content": "Kinetic parameters of morphine and azidomorphine derivatives as well as methionine enkephalin methylester were determined on the electrically stimulated isolated medial smooth muscle of the cat nictitating membrane. The organ was found to be a promising in vitro model for testing the action of opiate agonists on opiate B receptors.", "contents": "The isolated nictitating membrane of the cat. A new model for the study of narcotic analgesics. Kinetic parameters of morphine and azidomorphine derivatives as well as methionine enkephalin methylester were determined on the electrically stimulated isolated medial smooth muscle of the cat nictitating membrane. The organ was found to be a promising in vitro model for testing the action of opiate agonists on opiate B receptors."}
{"id": "PMID:29320", "title": "Chemical stability of prostacyclin (PGI2) in aqueous solutions.", "content": "The rate constant for the hydrolysis of prostacyclin (PGI2) to 6-keto-PGF1alpha was measured by monitoring the UV spectral change, over a pH range 6 to 10 at 25 degrees C and the total ionic strength of 0.5 M. The first-order rate constant (kdegreesobs) extrapolated to zero buffer concentration follows an expression, kdegreesobs = kH+ (H+), where kH+ is a second-order rate constant for the specific acid catalyzed hydrolysis. The value of kH+ obtained (3.71 x 10(4) sec-1 M-1) Is estimated approximately 700-fold greater than a kH+ value expected from the hydrolysis of other vinyl ethers. Such an unusually high reactivity of PGI2 even for a vinyl ether is attributed to a possible ring strain release that would occur upon the rate controlling protonation of C5. A Br\u00f8nsted slope (alpha) of 0.71 was obtained for the acid (including H3O+) catalytic constants, from which a pH independent first-order rate constant for the spontaneous hydrolysis (catalyzed by H2O as a general acid) was estimated to be 1.3 x 10(-6) sec-1. An apparent activation energy (Ea) of 11.85 Kcal/mole was obtained for the hydrolysis at pH 7.48, from which a half-life of PGI2 at 4 degrees C was estimated to be approximately 14.5 min. when the total phosphate concentration is 0.165 M (cf. 3.5 min. at 25 degrees C).", "contents": "Chemical stability of prostacyclin (PGI2) in aqueous solutions. The rate constant for the hydrolysis of prostacyclin (PGI2) to 6-keto-PGF1alpha was measured by monitoring the UV spectral change, over a pH range 6 to 10 at 25 degrees C and the total ionic strength of 0.5 M. The first-order rate constant (kdegreesobs) extrapolated to zero buffer concentration follows an expression, kdegreesobs = kH+ (H+), where kH+ is a second-order rate constant for the specific acid catalyzed hydrolysis. The value of kH+ obtained (3.71 x 10(4) sec-1 M-1) Is estimated approximately 700-fold greater than a kH+ value expected from the hydrolysis of other vinyl ethers. Such an unusually high reactivity of PGI2 even for a vinyl ether is attributed to a possible ring strain release that would occur upon the rate controlling protonation of C5. A Br\u00f8nsted slope (alpha) of 0.71 was obtained for the acid (including H3O+) catalytic constants, from which a pH independent first-order rate constant for the spontaneous hydrolysis (catalyzed by H2O as a general acid) was estimated to be 1.3 x 10(-6) sec-1. An apparent activation energy (Ea) of 11.85 Kcal/mole was obtained for the hydrolysis at pH 7.48, from which a half-life of PGI2 at 4 degrees C was estimated to be approximately 14.5 min. when the total phosphate concentration is 0.165 M (cf. 3.5 min. at 25 degrees C)."}
{"id": "PMID:29326", "title": "Retained inhibition of the beta receptor by propranolol after preincubation and washout.", "content": "Mouse thymus cells possess a B2-adrenergic receptor and, when centrifuged through a solution of propanolol at 5 degrees and washed three times, will produce reduced amounts of cyclic AMP during a 5 minute challenge with isoproterenol at room temperature. Depending on the concentration and nature of the antagonist, the retained inhibition may be greater or less than that seen when it is added with the agonist. This retained inhibition is readily reversed at 37 degrees even in the absence of the agonist. These effects can also be demonstrated with rat erythrocytes and with their subsequently prepared ghosts making it most likely that they result from the specific and tight binding of the antagonist to the beta receptor.", "contents": "Retained inhibition of the beta receptor by propranolol after preincubation and washout. Mouse thymus cells possess a B2-adrenergic receptor and, when centrifuged through a solution of propanolol at 5 degrees and washed three times, will produce reduced amounts of cyclic AMP during a 5 minute challenge with isoproterenol at room temperature. Depending on the concentration and nature of the antagonist, the retained inhibition may be greater or less than that seen when it is added with the agonist. This retained inhibition is readily reversed at 37 degrees even in the absence of the agonist. These effects can also be demonstrated with rat erythrocytes and with their subsequently prepared ghosts making it most likely that they result from the specific and tight binding of the antagonist to the beta receptor."}
{"id": "PMID:29327", "title": "Effect of benzodiazepine derivatives on human blood cholinesterase in vitro.", "content": "The in vitro effect of ten benzodiazepine derivatives on the cholinesterases of human plasma and red cells was determined. Flurazepam, temazepam, lorazepam, flunitrazepam and diazepam had an inhibitory effect on plasma cholinesterase of 60--90 per cent and, with the exception of lorazepam, an inhibitory effect of 40--50 per cent on red cell cholinesterase. Clonazepam, oxazepam, chlordiazepoxide, nitrazepam and bromazepam had comparatively minor effects on both enzymes", "contents": "Effect of benzodiazepine derivatives on human blood cholinesterase in vitro. The in vitro effect of ten benzodiazepine derivatives on the cholinesterases of human plasma and red cells was determined. Flurazepam, temazepam, lorazepam, flunitrazepam and diazepam had an inhibitory effect on plasma cholinesterase of 60--90 per cent and, with the exception of lorazepam, an inhibitory effect of 40--50 per cent on red cell cholinesterase. Clonazepam, oxazepam, chlordiazepoxide, nitrazepam and bromazepam had comparatively minor effects on both enzymes"}
{"id": "PMID:29330", "title": "[Physiological trials with MIF-I in Parkinson's disease (author's transl)].", "content": "The writers present some physiological (and not therapeutic) acute and sub-acute trials with tripeptide: L-propyl-L-leucyl-glycine amide (M.I.F.-I) in Parkinson's Disease. This work confirms the earlier observation that M.I.F.-I employed alone or in combination with Levodopa is active against Parkinson's disease. The writers evoke the hypothesis that this action takes place at the postsynaptic receptors, whose configuration may be modified in the sense of a hypersensitivity. These studies justify undertaking a series of controlled therapeutic trials when the cost of the product permits and as well instituting development work on analogues active orally.", "contents": "[Physiological trials with MIF-I in Parkinson's disease (author's transl)]. The writers present some physiological (and not therapeutic) acute and sub-acute trials with tripeptide: L-propyl-L-leucyl-glycine amide (M.I.F.-I) in Parkinson's Disease. This work confirms the earlier observation that M.I.F.-I employed alone or in combination with Levodopa is active against Parkinson's disease. The writers evoke the hypothesis that this action takes place at the postsynaptic receptors, whose configuration may be modified in the sense of a hypersensitivity. These studies justify undertaking a series of controlled therapeutic trials when the cost of the product permits and as well instituting development work on analogues active orally."}
{"id": "PMID:29337", "title": "[Neuroleptics and sexual dysfunction in man. Neuroendocrine aspects].", "content": "Sexual behaviour and fertility of schizophrenic patients are discussed. The various sexual dysfunctions induced by neuroleptics, such as decrease in libido, troubles of ejaculation and impotence, are described and related to their various mechanisms of action. The central antidopaminergic effect of neuroleptics would be responsible for an overall non-specific decrease in libido. Their effect upon the autonomous nervous system would explain ejaculation disturbances. Their endocrine action (increase in prolactine) would produce impotence. The possibility of treatment of these endocrinological troubles by bromocriptine is discussed.", "contents": "[Neuroleptics and sexual dysfunction in man. Neuroendocrine aspects]. Sexual behaviour and fertility of schizophrenic patients are discussed. The various sexual dysfunctions induced by neuroleptics, such as decrease in libido, troubles of ejaculation and impotence, are described and related to their various mechanisms of action. The central antidopaminergic effect of neuroleptics would be responsible for an overall non-specific decrease in libido. Their effect upon the autonomous nervous system would explain ejaculation disturbances. Their endocrine action (increase in prolactine) would produce impotence. The possibility of treatment of these endocrinological troubles by bromocriptine is discussed."}
{"id": "PMID:29334", "title": "Lymphocyte changes after long-term therapy of some neurological diseases.", "content": "Hematologic investigations were carried out in 50 patients with various forms of epilepsy, aged 20 to 50 years, who had been treated for different periods of time with antiepileptic and neuroleptic drugs such as primidon, luminal and prasine. All the cytomorphological and cytochemical studies concerned the white blood cells, especially lymphocytes, and their transformation into plasma cells and histiomonocytes. The cytochemical investigations referred particularly to nucleolar-RNA, glycogen and lipid cellular content. The results obtained showed that the lymphocyte count and mostly that of the large and medium lymphocytes, may reach twice the normal or more. The transition forms towards histiomonocytes and plasma cells were quite frequent. Cytochemically, a variable state of reactivity of the nucleolar apparatus was demonstrated, as well as certain changes of the carbohydrate and lipid metabolism. The influence of such changes on the cellular and humoral immunity of the respective patients is discussed. Emphasis is also laid on the utility of such investigations for the detection of the untoward effects of antiepileptic and neuroleptic drugs on hematopoiesis.", "contents": "Lymphocyte changes after long-term therapy of some neurological diseases. Hematologic investigations were carried out in 50 patients with various forms of epilepsy, aged 20 to 50 years, who had been treated for different periods of time with antiepileptic and neuroleptic drugs such as primidon, luminal and prasine. All the cytomorphological and cytochemical studies concerned the white blood cells, especially lymphocytes, and their transformation into plasma cells and histiomonocytes. The cytochemical investigations referred particularly to nucleolar-RNA, glycogen and lipid cellular content. The results obtained showed that the lymphocyte count and mostly that of the large and medium lymphocytes, may reach twice the normal or more. The transition forms towards histiomonocytes and plasma cells were quite frequent. Cytochemically, a variable state of reactivity of the nucleolar apparatus was demonstrated, as well as certain changes of the carbohydrate and lipid metabolism. The influence of such changes on the cellular and humoral immunity of the respective patients is discussed. Emphasis is also laid on the utility of such investigations for the detection of the untoward effects of antiepileptic and neuroleptic drugs on hematopoiesis."}
{"id": "PMID:29338", "title": "[Histamine H-2 receptor antagonists and medical treatment of Zollinger-Ellison syndrome].", "content": "Cimetidine was studied in 8 cases of Zollinger-Ellison syndrome. The average dose was 1,2 g a day for 14 to 195 days. The treatment was remarkably effective in 2 cases, but only partial or temporary improvement was noted in 3 other cases. The last 3 patients failed to respond to treatment. The possibility of a rebound phenomenon requires strict clinical and biological supervision.", "contents": "[Histamine H-2 receptor antagonists and medical treatment of Zollinger-Ellison syndrome]. Cimetidine was studied in 8 cases of Zollinger-Ellison syndrome. The average dose was 1,2 g a day for 14 to 195 days. The treatment was remarkably effective in 2 cases, but only partial or temporary improvement was noted in 3 other cases. The last 3 patients failed to respond to treatment. The possibility of a rebound phenomenon requires strict clinical and biological supervision."}
{"id": "PMID:29340", "title": "Small cell carcinoma of the lung: cellular origin and relationship to other neoplasms.", "content": "Many small cell carcinomas share morphological and physiological characteristics with normal and neoplastic cells of Pearse's APUD series, including pulmonary APUD cells and pulmonary carcinoid tumors. There is very likely more than one type of APUD cell in the lung, and conclusions that small cell carcinomas and carcinoids reflect neoplastic transformation of the same cell type are probably premature. The embryoogic lineage of pulmonary APUD cells is at present uncertain. The hypothesis that all APUD cells are derived from the neural crest is no longer tenable, and although some evidence does suggest a neural contribution to the pulmonary epithelium, additional embryologic studies are required. Some tumors that currently are classified as small cell carcinomas probably do not have APUD cell characteristics, and still others appear to have both APUD and non-APUD features. A  subclassification of small cell carcinomas based on a combination of physiological and morphological features might prove to be of prognostic and therapeutic value, but current knowledge probably would not provide a sufficient foundation for a reliable or practical subclassification. Multidisciplinary studies of the differentiation and function of normal and neoplastic APUD cells in the lungs and elsewhere are needed.", "contents": "Small cell carcinoma of the lung: cellular origin and relationship to other neoplasms. Many small cell carcinomas share morphological and physiological characteristics with normal and neoplastic cells of Pearse's APUD series, including pulmonary APUD cells and pulmonary carcinoid tumors. There is very likely more than one type of APUD cell in the lung, and conclusions that small cell carcinomas and carcinoids reflect neoplastic transformation of the same cell type are probably premature. The embryoogic lineage of pulmonary APUD cells is at present uncertain. The hypothesis that all APUD cells are derived from the neural crest is no longer tenable, and although some evidence does suggest a neural contribution to the pulmonary epithelium, additional embryologic studies are required. Some tumors that currently are classified as small cell carcinomas probably do not have APUD cell characteristics, and still others appear to have both APUD and non-APUD features. A  subclassification of small cell carcinomas based on a combination of physiological and morphological features might prove to be of prognostic and therapeutic value, but current knowledge probably would not provide a sufficient foundation for a reliable or practical subclassification. Multidisciplinary studies of the differentiation and function of normal and neoplastic APUD cells in the lungs and elsewhere are needed."}
{"id": "PMID:29343", "title": "Maternal blood gas status of four racial groups in late pregnancy A preliminary study.", "content": "The blood gas/acid-base status of normal healthy Black, Indian, Coloured and White pregnant women was measured. All groups exhibited evidence of hyperventilation (decreased) PaCO2 relative to the non-pregnant state, with compensatory metabolic adjustment. Arterial oxygen tensions (PaO2) were significantly lower in the Black and Indian groups compared with their White counterparts (P less than 0,01). Differences between the former two series and the Coloured group, however, just failed to reach statistically significant levels (0,1 less than P less than 0,05). The possible causes of a lowered PaO2 during pregnancy and their relevance to obstetric anaesthesia are discussed. A further study using a more sophisticated protocol is planned in an attempt to delineate the causes of these important differences.", "contents": "Maternal blood gas status of four racial groups in late pregnancy A preliminary study. The blood gas/acid-base status of normal healthy Black, Indian, Coloured and White pregnant women was measured. All groups exhibited evidence of hyperventilation (decreased) PaCO2 relative to the non-pregnant state, with compensatory metabolic adjustment. Arterial oxygen tensions (PaO2) were significantly lower in the Black and Indian groups compared with their White counterparts (P less than 0,01). Differences between the former two series and the Coloured group, however, just failed to reach statistically significant levels (0,1 less than P less than 0,05). The possible causes of a lowered PaO2 during pregnancy and their relevance to obstetric anaesthesia are discussed. A further study using a more sophisticated protocol is planned in an attempt to delineate the causes of these important differences."}
{"id": "PMID:29347", "title": "Antacid properties of a sodium citrate preparation.", "content": "A sodium citrate preparation (Citro-Soda; Abbott) given in single doses of 4 or 12 g, satisfactorily increased the pH level of urine without affecting the systemic acid-base balance. When the sodium citrate preparation was administered in the 12-g single dose the gastric pH level was raised above 3,0 in a significant number of subjects. Similar results were obtained with both single doses (4 and 12 g) after 3 - 6 days of continuous therapy at the appropriate dose given every 6 hours. It is concluded that the urine-alkalinizing sodium citrate preparation reduced intragastric acidity significantly.", "contents": "Antacid properties of a sodium citrate preparation. A sodium citrate preparation (Citro-Soda; Abbott) given in single doses of 4 or 12 g, satisfactorily increased the pH level of urine without affecting the systemic acid-base balance. When the sodium citrate preparation was administered in the 12-g single dose the gastric pH level was raised above 3,0 in a significant number of subjects. Similar results were obtained with both single doses (4 and 12 g) after 3 - 6 days of continuous therapy at the appropriate dose given every 6 hours. It is concluded that the urine-alkalinizing sodium citrate preparation reduced intragastric acidity significantly."}
{"id": "PMID:29348", "title": "Assessment of a diagnostic dip-stick for assaying plasma or serum pseudocholinesterase activity.", "content": "A diagnostic dip-stick for measuring pseudocholinesterase activity has been assessed by 4 participants and compared with a standard spectrophotometric method. Duplicate dip-stick estimations (measured in kU/l) corresponded closely, and concurrence between participants was good. The dip-stick estimate of cholinesterase was consistently lower than the spectrophotometric value; the magnitude of this deviation depended on the absolute enzyme activity. With enzyme activities of up to 1 kU/l the dip-stick value was 1 unit lower. Between 1 and 4 kU/l the dip-stick estimate compared well with the spectrophotometric value. From 5 to 7 kU/l and beyond 7 kU/l the negative deviation recorded by the dip-stick increased to 2 units or more. Normal enzyme activity is 3 - 6 kU/l. Over the 1 - 4 kU/l range the method is most accurate, thus negative deviation below 1 kU/l or above 4 kU/l is generally diagnostically irrelevant. On the basis of cost, convenience, speed and accuracy this method will suffice in the absence of sophisticated assay facilities.", "contents": "Assessment of a diagnostic dip-stick for assaying plasma or serum pseudocholinesterase activity. A diagnostic dip-stick for measuring pseudocholinesterase activity has been assessed by 4 participants and compared with a standard spectrophotometric method. Duplicate dip-stick estimations (measured in kU/l) corresponded closely, and concurrence between participants was good. The dip-stick estimate of cholinesterase was consistently lower than the spectrophotometric value; the magnitude of this deviation depended on the absolute enzyme activity. With enzyme activities of up to 1 kU/l the dip-stick value was 1 unit lower. Between 1 and 4 kU/l the dip-stick estimate compared well with the spectrophotometric value. From 5 to 7 kU/l and beyond 7 kU/l the negative deviation recorded by the dip-stick increased to 2 units or more. Normal enzyme activity is 3 - 6 kU/l. Over the 1 - 4 kU/l range the method is most accurate, thus negative deviation below 1 kU/l or above 4 kU/l is generally diagnostically irrelevant. On the basis of cost, convenience, speed and accuracy this method will suffice in the absence of sophisticated assay facilities."}
{"id": "PMID:29349", "title": "Clinical usefulness of the beta-adrenergic antagonists.", "content": "The pharmacology of the beta-adrenergic antagonists, particularly their role as competitive antagonists at the receptor site, is discussed. The clinical use of these agents is listed and a detailed outline of their use in angina pectoris, hypertension and conditions associated with increased sympathetic activity is provided. The relative contraindications to the use of beta-adrenergic antagonists are summarized and the pharmacology of those drug interactions involving these agents is discussed. A thorough understanding of the pharmacology and therapeutics of these agents, which interfere with physiological function, is mandatory prior to their clinical use.", "contents": "Clinical usefulness of the beta-adrenergic antagonists. The pharmacology of the beta-adrenergic antagonists, particularly their role as competitive antagonists at the receptor site, is discussed. The clinical use of these agents is listed and a detailed outline of their use in angina pectoris, hypertension and conditions associated with increased sympathetic activity is provided. The relative contraindications to the use of beta-adrenergic antagonists are summarized and the pharmacology of those drug interactions involving these agents is discussed. A thorough understanding of the pharmacology and therapeutics of these agents, which interfere with physiological function, is mandatory prior to their clinical use."}
{"id": "PMID:29354", "title": "Teratogenic action of bis(dichloroacetyl)diamine on rats: patterns of malformations produced in high incidence at time-limited periods of development.", "content": "Win 18,446, a bis(dichloroacetyl)diamine, is a drug that was previously shown to suppress spermatogenesis and to be an effective oral abortifacient in rats. The present study shows that the drug is capable of producing characteristic congenital malformations in high incidence, by a single treatment, and with high survival of fetuses to day 21. Gestation day 11 is the most sensitive time. The teratologies obtained after various schedules of treatment include malformations of the snout (100%), septal heart defects (100%) diaphragmatic hernias (100%), cryptorchism (100%), cervical pockets (100%) and absent or small irregular thymus (92%). Some of these data, namely of the  heart, face and thymus, cluster in patterns that indicate that the action of the drug is upon a time-resistricted developmental process. These periods of sensitivity are subsiding or have ended before primordia of these structures appear, but they coincide with the proliferation and migration of those mesenchyme cells that will eventually form or contribute to the structures affected. It is postulated that the drug acts on these mesenchyme cells, or on the extracellular matrix that provides the necessary framework for their dispersal.", "contents": "Teratogenic action of bis(dichloroacetyl)diamine on rats: patterns of malformations produced in high incidence at time-limited periods of development. Win 18,446, a bis(dichloroacetyl)diamine, is a drug that was previously shown to suppress spermatogenesis and to be an effective oral abortifacient in rats. The present study shows that the drug is capable of producing characteristic congenital malformations in high incidence, by a single treatment, and with high survival of fetuses to day 21. Gestation day 11 is the most sensitive time. The teratologies obtained after various schedules of treatment include malformations of the snout (100%), septal heart defects (100%) diaphragmatic hernias (100%), cryptorchism (100%), cervical pockets (100%) and absent or small irregular thymus (92%). Some of these data, namely of the  heart, face and thymus, cluster in patterns that indicate that the action of the drug is upon a time-resistricted developmental process. These periods of sensitivity are subsiding or have ended before primordia of these structures appear, but they coincide with the proliferation and migration of those mesenchyme cells that will eventually form or contribute to the structures affected. It is postulated that the drug acts on these mesenchyme cells, or on the extracellular matrix that provides the necessary framework for their dispersal."}
{"id": "PMID:29357", "title": "Stabilization of interferons.", "content": "It is now obvious that there are a number of factors which can influence the stability of interferons. Since human fibroblast interferon is especially unstable both to heat and mechanical stress, the use of stabilizing conditions such as low pH or thioctic acid should facilitate purification and concentration of this interferon. Leukocyte interferon, on the other hand, seems to be more stable even when highly purified; however, losses in activity can occur in very dilute solutions containing low concentrations of protein. Inactivation during storage of interferons may be avoided by using freeze-dried preparations. In order to generate large quantities of purified, stable interferons for clinical use, there is a need to establish an armamentarium of different nontoxic techniques and approaches that will enable investigators to stabilize human interferons at each step in preparation, processing, concentration, purification, shipment and storage.", "contents": "Stabilization of interferons. It is now obvious that there are a number of factors which can influence the stability of interferons. Since human fibroblast interferon is especially unstable both to heat and mechanical stress, the use of stabilizing conditions such as low pH or thioctic acid should facilitate purification and concentration of this interferon. Leukocyte interferon, on the other hand, seems to be more stable even when highly purified; however, losses in activity can occur in very dilute solutions containing low concentrations of protein. Inactivation during storage of interferons may be avoided by using freeze-dried preparations. In order to generate large quantities of purified, stable interferons for clinical use, there is a need to establish an armamentarium of different nontoxic techniques and approaches that will enable investigators to stabilize human interferons at each step in preparation, processing, concentration, purification, shipment and storage."}
{"id": "PMID:29362", "title": "Study on dissolution and disintegration of calcium bilirubinate stone.", "content": "When a slice of calcium bilirubinate stone was incubated in a solution of tetrasodium salt of ethylendiamine-tetraacetic acid (EDTA.4Na), a potent chelating agent, the solution exhibited a yellow brown tint, which was spectroscopically characteristic of bilirubin. Microscopic examination of the slice revealed dissolution of granules of calcium bilirubinate, leaving behind a reticular matrix of PAS-positive substance. The effect of EDTA.4Na was influenced by pH, being fully effective only at pH 10 or more, and by temperature and concentration as well. Simultaneous application of bile salt enhanced the activity of EDTA.4Na, hydrophilizing the gallstone surface to facilitate chelating reaction and also dissolving minor fatty components of the stone. Heparin at proper concentrations also promoted disintegration of the stone, changing surface potential of its constituent particles to the dispersion-prone charge. The effect of composite EDTA.4Na-bile salt-heparin was thus significantly greater than that of single EDTA.4Na. This mixture is promising for clinical application as a means of direct dissolution of residual gallstones.", "contents": "Study on dissolution and disintegration of calcium bilirubinate stone. When a slice of calcium bilirubinate stone was incubated in a solution of tetrasodium salt of ethylendiamine-tetraacetic acid (EDTA.4Na), a potent chelating agent, the solution exhibited a yellow brown tint, which was spectroscopically characteristic of bilirubin. Microscopic examination of the slice revealed dissolution of granules of calcium bilirubinate, leaving behind a reticular matrix of PAS-positive substance. The effect of EDTA.4Na was influenced by pH, being fully effective only at pH 10 or more, and by temperature and concentration as well. Simultaneous application of bile salt enhanced the activity of EDTA.4Na, hydrophilizing the gallstone surface to facilitate chelating reaction and also dissolving minor fatty components of the stone. Heparin at proper concentrations also promoted disintegration of the stone, changing surface potential of its constituent particles to the dispersion-prone charge. The effect of composite EDTA.4Na-bile salt-heparin was thus significantly greater than that of single EDTA.4Na. This mixture is promising for clinical application as a means of direct dissolution of residual gallstones."}
{"id": "PMID:29367", "title": "[Concentration of acid and basic proteins in the nuclei of hippocampal neurons and neuroglia of rat brain following elaboration of a passive avoidance conditioned reflex].", "content": "By means of two-wave-length visible cytophotometry, the content of acidic and basic proteins per cell nucleus was shown to increase in CA3 hippocampal neurons only 3 hours after the learning session of conditioned reflex of passive avoidance. The protein content in the nuclei of perineuronal neuroglia cells of CA3 hippocampus increased only 6 hours after the learning session. Biochemical mechanisms dealing with the process of learning are discussed.", "contents": "[Concentration of acid and basic proteins in the nuclei of hippocampal neurons and neuroglia of rat brain following elaboration of a passive avoidance conditioned reflex]. By means of two-wave-length visible cytophotometry, the content of acidic and basic proteins per cell nucleus was shown to increase in CA3 hippocampal neurons only 3 hours after the learning session of conditioned reflex of passive avoidance. The protein content in the nuclei of perineuronal neuroglia cells of CA3 hippocampus increased only 6 hours after the learning session. Biochemical mechanisms dealing with the process of learning are discussed."}
{"id": "PMID:29368", "title": "[Enzymologic study of the structural organization of the matrix or rat liver peroxisomes].", "content": "The effect of ionic strength and pH on the release of some enzymes of the matrix of peroxisomes in rat's liver was studied. Catalase, L ALpha-hydroxy acid oxidase, isocitrate dehydrogenase, glycerophosphate dehydrogenase and lactate dehydrogenase were easily released from the particles during their lysis and treatment with 0.16 M KCl, whereas urate oxidase, NADH cytochrome c reductase and D-amino acid oxidase were not solubilized. After the solubilization of peroxisomal membrane by 0.2% Triton X-100, the remaining core contained about 50% amino acid oxidase activity, and had 1.28--1.30 g/cm3 density. These results suggest that D-amino acid oxidase associates with urate oxidase in the peroxisomal core.", "contents": "[Enzymologic study of the structural organization of the matrix or rat liver peroxisomes]. The effect of ionic strength and pH on the release of some enzymes of the matrix of peroxisomes in rat's liver was studied. Catalase, L ALpha-hydroxy acid oxidase, isocitrate dehydrogenase, glycerophosphate dehydrogenase and lactate dehydrogenase were easily released from the particles during their lysis and treatment with 0.16 M KCl, whereas urate oxidase, NADH cytochrome c reductase and D-amino acid oxidase were not solubilized. After the solubilization of peroxisomal membrane by 0.2% Triton X-100, the remaining core contained about 50% amino acid oxidase activity, and had 1.28--1.30 g/cm3 density. These results suggest that D-amino acid oxidase associates with urate oxidase in the peroxisomal core."}
{"id": "PMID:29372", "title": "[Acid-base state disorders and their correction in acute mesenteric vascular obstruction].", "content": "The results of the investigation of main indices of acid-base equilibrium in 28 patients with acute obstruction of the mesenteric vessels are set forth. 12 patients out of 28 developed subcompensated or decompensated metabolic acidosis. The authors believe that the correction of acid-base equilibrium disorders is an efficacious factor of intense therapy and recommend to use it at all the stages of the treatment.", "contents": "[Acid-base state disorders and their correction in acute mesenteric vascular obstruction]. The results of the investigation of main indices of acid-base equilibrium in 28 patients with acute obstruction of the mesenteric vessels are set forth. 12 patients out of 28 developed subcompensated or decompensated metabolic acidosis. The authors believe that the correction of acid-base equilibrium disorders is an efficacious factor of intense therapy and recommend to use it at all the stages of the treatment."}
{"id": "PMID:29379", "title": "Absorption of the beta-adrenergic-blocking agent, nadolol, by mice, rats, hamsters, rabbits, dogs, monkeys, and man: an unusual species difference.", "content": "1. Dogs absorbed [14C]nadolol almost completely (88--104%) after oral administration of 10--75 mg/kg. In contrast, mice, rats, hamsters, and rabbits, given oral doses of 20 mg/kg, absorbed, at most, 25%. After administration of oral doses of 2--75 mg/kg, monkeys absorbed no more than an average of 30%. Six monkeys given oral doses of 10 mg/kg absorbed 12--44%. 2. In rats, [14C]nadolol was orally absorbed to an average of 13.7--17.5%, whether given in suspension or in solution, indicating that absorption was not limited by rate of dissolution nor by solubility. 3. Mildly hypertensive humans given single doses of [14C]nadolol (2 or 80 mg, orally) and normal subjects given single doses (10 mg, orally) absorbed an average of 20.4--33.3%.", "contents": "Absorption of the beta-adrenergic-blocking agent, nadolol, by mice, rats, hamsters, rabbits, dogs, monkeys, and man: an unusual species difference. 1. Dogs absorbed [14C]nadolol almost completely (88--104%) after oral administration of 10--75 mg/kg. In contrast, mice, rats, hamsters, and rabbits, given oral doses of 20 mg/kg, absorbed, at most, 25%. After administration of oral doses of 2--75 mg/kg, monkeys absorbed no more than an average of 30%. Six monkeys given oral doses of 10 mg/kg absorbed 12--44%. 2. In rats, [14C]nadolol was orally absorbed to an average of 13.7--17.5%, whether given in suspension or in solution, indicating that absorption was not limited by rate of dissolution nor by solubility. 3. Mildly hypertensive humans given single doses of [14C]nadolol (2 or 80 mg, orally) and normal subjects given single doses (10 mg, orally) absorbed an average of 20.4--33.3%."}
{"id": "PMID:29380", "title": "Glutamate metabolism in a monokaryon of Coprinus cinereus.", "content": "The possible involvement of the glutamine synthetase/glutamate synthase pathway in ammonia assimilation is reported in a monokaryon of Coprinus cinereus.", "contents": "Glutamate metabolism in a monokaryon of Coprinus cinereus. The possible involvement of the glutamine synthetase/glutamate synthase pathway in ammonia assimilation is reported in a monokaryon of Coprinus cinereus."}
{"id": "PMID:29381", "title": "Microbial biodegradation of cellophase.", "content": "The microbial biodegradation of cellophane (U.C.B.--Division Sidac) was studied. Preliminary experiments with pure cultures of seven cellulolytic microorganisms (Aspergillus sp., Penicillium sp., Chaetomium crispatum, Ch. globosum, Sclerotium rolfsii and two actinomycetes) revealed that the substrate as such was very recalcitrant, probably due to the occurrence of insoluble coating agents. Therefore, mixed cultures of the above mentioned cellulolytic microorganisms were used as inoculum. The cellophane showed a slow microbial degradation which starts only after 37 days of incubation. This long lag-phase is due to the unaltered presence of the coating agents. However, when the coating agents are extracted with tetrahydrofuran, the biodegradation starts after 10 days, resulting in a biodegradation rate of 85% after 52 days of incubation and a protein content of 30%. The endproduct (30% protein, 60% soluble sugars, 10% residual substrate) will probably be useful as compost.", "contents": "Microbial biodegradation of cellophase. The microbial biodegradation of cellophane (U.C.B.--Division Sidac) was studied. Preliminary experiments with pure cultures of seven cellulolytic microorganisms (Aspergillus sp., Penicillium sp., Chaetomium crispatum, Ch. globosum, Sclerotium rolfsii and two actinomycetes) revealed that the substrate as such was very recalcitrant, probably due to the occurrence of insoluble coating agents. Therefore, mixed cultures of the above mentioned cellulolytic microorganisms were used as inoculum. The cellophane showed a slow microbial degradation which starts only after 37 days of incubation. This long lag-phase is due to the unaltered presence of the coating agents. However, when the coating agents are extracted with tetrahydrofuran, the biodegradation starts after 10 days, resulting in a biodegradation rate of 85% after 52 days of incubation and a protein content of 30%. The endproduct (30% protein, 60% soluble sugars, 10% residual substrate) will probably be useful as compost."}
{"id": "PMID:29386", "title": "Kinetic studies on the formation of nitrosamines I. Formation of dimethylnitrosamine in aqeous solution of perchloric acid.", "content": "The kinetics of nitrosation of dimethylamine (DMA) in aqueous perchloric acid solution have been studied using a differential spectrophotometric technique. The rate law is Initial rate = e[DMA]0 [nitrite]2 0 [H+]/(f + [H+])2 where [DMA]0 and [nitrite]0 represent initial stoichiometric concentrations. At 310.0 K and mu = 2.0 M, e = (2.2 +/- 0.2) X 10(-5) M-1 s-1 and f = (1.28 +/- 0.02) X 10(-3) M. The associated activation energy is 56 +/- 3 kJ mol-1. A clear inhibition of the nitrosation rate by ionic strength has been observed in which only the kinetic parameter (f) has an effective change. It is concluded that under the experimental conditions of this work only the dinitrogen trioxid is the effective carrier for the nitrosation.", "contents": "Kinetic studies on the formation of nitrosamines I. Formation of dimethylnitrosamine in aqeous solution of perchloric acid. The kinetics of nitrosation of dimethylamine (DMA) in aqueous perchloric acid solution have been studied using a differential spectrophotometric technique. The rate law is Initial rate = e[DMA]0 [nitrite]2 0 [H+]/(f + [H+])2 where [DMA]0 and [nitrite]0 represent initial stoichiometric concentrations. At 310.0 K and mu = 2.0 M, e = (2.2 +/- 0.2) X 10(-5) M-1 s-1 and f = (1.28 +/- 0.02) X 10(-3) M. The associated activation energy is 56 +/- 3 kJ mol-1. A clear inhibition of the nitrosation rate by ionic strength has been observed in which only the kinetic parameter (f) has an effective change. It is concluded that under the experimental conditions of this work only the dinitrogen trioxid is the effective carrier for the nitrosation."}
{"id": "PMID:29388", "title": "Pyruvate and citrate metabolism in the muscle tissue of Ascaris lumbricoides.", "content": "Aconitase and NAD linked isocitrate dehydrogenase were present in Ascaris lumbricoides muscle at only very low activities, whilst there were significant levels of citrate synthase, NADP linked isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase and succinic thiokinase. Pyruvate dehydrogenase was present in A. lumbricoides muscle at levels comparable with mammalian tissues and results suggest that it is modulated via a phosphotransferase/phosphatase system. The tricarboxylic acid cycle intermediates, citrate, isocitrate and 2-oxoglutarate were all detected in freeze clamped muscle, but their steady state levels were considerably lower than those found in mammalian tissues.", "contents": "Pyruvate and citrate metabolism in the muscle tissue of Ascaris lumbricoides. Aconitase and NAD linked isocitrate dehydrogenase were present in Ascaris lumbricoides muscle at only very low activities, whilst there were significant levels of citrate synthase, NADP linked isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase and succinic thiokinase. Pyruvate dehydrogenase was present in A. lumbricoides muscle at levels comparable with mammalian tissues and results suggest that it is modulated via a phosphotransferase/phosphatase system. The tricarboxylic acid cycle intermediates, citrate, isocitrate and 2-oxoglutarate were all detected in freeze clamped muscle, but their steady state levels were considerably lower than those found in mammalian tissues."}
{"id": "PMID:29389", "title": "Investigations into the free-living phase of the cat hookworm life cycle.", "content": "Laboratory studies were undertaken to evaluate the role of environmental factors on the development of free-living stages of the cat hookworm Ancylostoma tubaeforme. An index of development calculated from the proportion of eggs that developed to the infective stage and the reciprocal of the development period, has suggested that the absence of 'high' temperatures (26 degrees - 30 degrees C) would significantly affect the L3 population in contaminated soils. There were, however, no significant differences in the size and lipid content of L3 that had developed at the different temperatures.", "contents": "Investigations into the free-living phase of the cat hookworm life cycle. Laboratory studies were undertaken to evaluate the role of environmental factors on the development of free-living stages of the cat hookworm Ancylostoma tubaeforme. An index of development calculated from the proportion of eggs that developed to the infective stage and the reciprocal of the development period, has suggested that the absence of 'high' temperatures (26 degrees - 30 degrees C) would significantly affect the L3 population in contaminated soils. There were, however, no significant differences in the size and lipid content of L3 that had developed at the different temperatures."}
{"id": "PMID:29398", "title": "[Japanese methods of psychotherapy and their socio-cultural determinants. Impressions from Japan together with a report on the IV Congress of the International College of Psychosomatic Medicine, Sept. 5--9, 1977 in Kyoto].", "content": "Impressions of a congress-visiting-journey through the highly-industrialized far-east Japan are the background for description of specific Japanese Psychotherapeutic-technics f.i.: the Morita-therapy, Naikan-therapy and the Fasten-therapy. To the analytically trained Psychosomatic-specialist of western mentality those medical applications appear rather bewildering if not frightening. Their psychodynamic and their effectiveness become more understandable regarding the social-cultural conditions in modern Japan founded and grown on a tradition thousands of years old. Psychoanalysis can't prosper there. During the congress of the ICPM (International College of Psychosomatic Medicine) in Kyoto it became evident to the author by visits to clinics and above all by experience of typical Japanese travelling impressions, how much just psychotherapy and it's special drive-dynamical intentions are to a major degree depending on social-cultural development, the norms of value, the religion and the philosophy of a society.--Nippon is unique--strange and fascinating.", "contents": "[Japanese methods of psychotherapy and their socio-cultural determinants. Impressions from Japan together with a report on the IV Congress of the International College of Psychosomatic Medicine, Sept. 5--9, 1977 in Kyoto]. Impressions of a congress-visiting-journey through the highly-industrialized far-east Japan are the background for description of specific Japanese Psychotherapeutic-technics f.i.: the Morita-therapy, Naikan-therapy and the Fasten-therapy. To the analytically trained Psychosomatic-specialist of western mentality those medical applications appear rather bewildering if not frightening. Their psychodynamic and their effectiveness become more understandable regarding the social-cultural conditions in modern Japan founded and grown on a tradition thousands of years old. Psychoanalysis can't prosper there. During the congress of the ICPM (International College of Psychosomatic Medicine) in Kyoto it became evident to the author by visits to clinics and above all by experience of typical Japanese travelling impressions, how much just psychotherapy and it's special drive-dynamical intentions are to a major degree depending on social-cultural development, the norms of value, the religion and the philosophy of a society.--Nippon is unique--strange and fascinating."}
{"id": "PMID:29417", "title": "Factors affecting the microbial and chemical composition of silage. III. Effect of urea additions on maize silage.", "content": "The effect of urea additions on the microbiological and chemical properties of silage, produced from young maize plants (Darawa stage), was studied. Urea treatments, i.e., 0.25%, 0.50%, 0.75%, and 1.00%, stimulated higher densities of the desired microorganisms than the control, while undesired organisms showed lower counts (proteolytic and saccharolytic anaerobes). Addition of 0.25 to 0.50% or urea resulted in the production of high quality silage with pleasant small and high nutritive value, as confirmed by the various microbiological and chemical analyses conducted. Higher levels (0.75 and 1.00%) of urea decreased the quality of the product.", "contents": "Factors affecting the microbial and chemical composition of silage. III. Effect of urea additions on maize silage. The effect of urea additions on the microbiological and chemical properties of silage, produced from young maize plants (Darawa stage), was studied. Urea treatments, i.e., 0.25%, 0.50%, 0.75%, and 1.00%, stimulated higher densities of the desired microorganisms than the control, while undesired organisms showed lower counts (proteolytic and saccharolytic anaerobes). Addition of 0.25 to 0.50% or urea resulted in the production of high quality silage with pleasant small and high nutritive value, as confirmed by the various microbiological and chemical analyses conducted. Higher levels (0.75 and 1.00%) of urea decreased the quality of the product."}
{"id": "PMID:29418", "title": "Serum-albumin agar used as slant for the differentiation between Trichophyton rubrum and Trichophyton mentagrophytes: specific reg pigmentation of T. rubrum.", "content": "Trichophyton rubrum strains freshly isolated from clinical material exhibited red pigment formation within 7 days at 26 degrees C on slant serum-albumin agar, initial pH 7.0. In Trichophyton mentagrophytes strains this phenomenon could not be observed. Since in the case of T. rubrum, yellow pigmentation will appear at an initial pH of 5.0, the use of initial pH values of 7.0 and 5.0 is recommended for diagnostic application of slant serum-albumin agar.", "contents": "Serum-albumin agar used as slant for the differentiation between Trichophyton rubrum and Trichophyton mentagrophytes: specific reg pigmentation of T. rubrum. Trichophyton rubrum strains freshly isolated from clinical material exhibited red pigment formation within 7 days at 26 degrees C on slant serum-albumin agar, initial pH 7.0. In Trichophyton mentagrophytes strains this phenomenon could not be observed. Since in the case of T. rubrum, yellow pigmentation will appear at an initial pH of 5.0, the use of initial pH values of 7.0 and 5.0 is recommended for diagnostic application of slant serum-albumin agar."}
{"id": "PMID:29419", "title": "[Neurologic syndromes in myocardial infarct patients during various stages of treatment].", "content": "The clinical picture of myocardial infarctions in complicated and manifold. A clinico-physiological analysis of neurological disorders gives ground to consider that in myocardial infarctions the process of irritation involves the peripheral vegetative apparatus and spinal segmental structures, as well as the hypothalmostem structures with the reticular formation, which in its turn is accompanied by disturbances of cortico-subcortical interrelationships. In patients with myocardial infarctions the vegetative disorders are of a regional character and may be expressed in symptomatology, characteristic of the stimulation of sympathetic ganglions on the left side, mainly in the stellate node.", "contents": "[Neurologic syndromes in myocardial infarct patients during various stages of treatment]. The clinical picture of myocardial infarctions in complicated and manifold. A clinico-physiological analysis of neurological disorders gives ground to consider that in myocardial infarctions the process of irritation involves the peripheral vegetative apparatus and spinal segmental structures, as well as the hypothalmostem structures with the reticular formation, which in its turn is accompanied by disturbances of cortico-subcortical interrelationships. In patients with myocardial infarctions the vegetative disorders are of a regional character and may be expressed in symptomatology, characteristic of the stimulation of sympathetic ganglions on the left side, mainly in the stellate node."}
{"id": "PMID:29420", "title": "The action of cathepsin B and collagenolytic cathepsin in the degradation of collagen.", "content": "Cathepsin B and collagenolytic cathepsin were obtained from bovine spleen and human placenta and identified as thiol proteinases. Both enzymes degraded insoluble fibrous collagen maximally at pH 3.5 and soluble monomeric collagen near pH 4.5. The response to activators and inhibitors was similar for both enzymes. Collagenolytic cathepsin was unable to degrade the synthetic substrates of cathepsin B and was also shown to differ in its physico-chemical properties. Minor differences were noted in the action of these cathepsins on insoluble fibrous collagen from different tissues. It was concluded that the rate and extent of the dissolution of fibrous collagen was determined by the number and location of the interchain cross-links, the amount of the associated non-collagenous components and the type of solvent ions, but not by the collagen phenotype.", "contents": "The action of cathepsin B and collagenolytic cathepsin in the degradation of collagen. Cathepsin B and collagenolytic cathepsin were obtained from bovine spleen and human placenta and identified as thiol proteinases. Both enzymes degraded insoluble fibrous collagen maximally at pH 3.5 and soluble monomeric collagen near pH 4.5. The response to activators and inhibitors was similar for both enzymes. Collagenolytic cathepsin was unable to degrade the synthetic substrates of cathepsin B and was also shown to differ in its physico-chemical properties. Minor differences were noted in the action of these cathepsins on insoluble fibrous collagen from different tissues. It was concluded that the rate and extent of the dissolution of fibrous collagen was determined by the number and location of the interchain cross-links, the amount of the associated non-collagenous components and the type of solvent ions, but not by the collagen phenotype."}
{"id": "PMID:29424", "title": "Reduced post-natal rise of testosterone in plasma of cryptorchid infants.", "content": "Plasma testosterone has been studied in 31 full-term male infants born with bilaterally undescended testes (14) or unilaterally undescended testis (17). From 10 to 89 days after birth, the post-natal testosterone rise was significantly lower in the 18 infants who remained cryptorchid at 4 months than in the 13 who underwent spontaneous testicular descensus and in the normal controls. Blunted post-natal Leydig cell secretion in cryptorchids may relate to a primary LH defect and could contribute to the impairment of both testicular descensus and maturation.", "contents": "Reduced post-natal rise of testosterone in plasma of cryptorchid infants. Plasma testosterone has been studied in 31 full-term male infants born with bilaterally undescended testes (14) or unilaterally undescended testis (17). From 10 to 89 days after birth, the post-natal testosterone rise was significantly lower in the 18 infants who remained cryptorchid at 4 months than in the 13 who underwent spontaneous testicular descensus and in the normal controls. Blunted post-natal Leydig cell secretion in cryptorchids may relate to a primary LH defect and could contribute to the impairment of both testicular descensus and maturation."}
{"id": "PMID:29425", "title": "In vitro and in vivo studies on Leydig cell function in old rats.", "content": "Young adult (3 months old) and old (26-28 months old) male Wistar rats were studied. Testicular weight was 1.66 g (range: 1.33--2.86) in the younger group and 1.62 g (range: 1.04--1.90) in the older group. The total Leydig cell volume as measured by a quantitative histometric method was significantly larger in the old animals (-x = 0.153 ml vs. -x = 0.089 ml). The testicular HCG binding capacity was 2.54 ng HCG per 100 mg tissue (range: 1.88--3.77) in the younger animals and 1.83 ng HCG per 100 mg tissue (range: 0.80--3.02) in the older ones (P less than 0.01). Plasma testosterone was on an average 242 ng/100 ml (range: 72--1162) in the young adult rats and 91 ng/100 ml (range: 23--277) in the older rats. Plasma LH was only slightly  (P less than 0.05) decreased and was 49 ng LH-RP-1/ml (range: 14--120) in the younger group and 40 ng LH-RP-1 ng/ml (range: 5--98) in the older. When the testicular tissue pieces were incubated with different doses of HCG or dibutyryl cAMP and testosterone production was measured, identical dose-response curves for old and young tissue were obtained. After in vitro incubation with a NADPH generating system, which under the conditions used was a much stronger stimulus for steroid biosynthesis than HCG or dibutyryl cAMP, the tissue of young rats produced about twice the amount of testosterone precursors (pregnenolone, progesterone, 17alpha-hydroxyprogesterone and androstenedione) than old tissue.", "contents": "In vitro and in vivo studies on Leydig cell function in old rats. Young adult (3 months old) and old (26-28 months old) male Wistar rats were studied. Testicular weight was 1.66 g (range: 1.33--2.86) in the younger group and 1.62 g (range: 1.04--1.90) in the older group. The total Leydig cell volume as measured by a quantitative histometric method was significantly larger in the old animals (-x = 0.153 ml vs. -x = 0.089 ml). The testicular HCG binding capacity was 2.54 ng HCG per 100 mg tissue (range: 1.88--3.77) in the younger animals and 1.83 ng HCG per 100 mg tissue (range: 0.80--3.02) in the older ones (P less than 0.01). Plasma testosterone was on an average 242 ng/100 ml (range: 72--1162) in the young adult rats and 91 ng/100 ml (range: 23--277) in the older rats. Plasma LH was only slightly  (P less than 0.05) decreased and was 49 ng LH-RP-1/ml (range: 14--120) in the younger group and 40 ng LH-RP-1 ng/ml (range: 5--98) in the older. When the testicular tissue pieces were incubated with different doses of HCG or dibutyryl cAMP and testosterone production was measured, identical dose-response curves for old and young tissue were obtained. After in vitro incubation with a NADPH generating system, which under the conditions used was a much stronger stimulus for steroid biosynthesis than HCG or dibutyryl cAMP, the tissue of young rats produced about twice the amount of testosterone precursors (pregnenolone, progesterone, 17alpha-hydroxyprogesterone and androstenedione) than old tissue."}
{"id": "PMID:29430", "title": "Influence of \"lytic cocktail\" on blood flow and oxygen consumption in the rat brain.", "content": "The influence of a sedative dose of \"lytic cocktail\" (chlorpromazine, promethazine and pethidine) on cerebral blood flow (CBF) and oxygen consumjtion (CMRO2) was tested in artificially ventilated rats, maintained on either 70% N2 or 70% N2O. When given alone, the lytic cocktail had no significant effect on CBF or CMRO2. However, in the presence of nitrous oxide there was a 25% reduction in blood flow and oxygen consumption.", "contents": "Influence of \"lytic cocktail\" on blood flow and oxygen consumption in the rat brain. The influence of a sedative dose of \"lytic cocktail\" (chlorpromazine, promethazine and pethidine) on cerebral blood flow (CBF) and oxygen consumjtion (CMRO2) was tested in artificially ventilated rats, maintained on either 70% N2 or 70% N2O. When given alone, the lytic cocktail had no significant effect on CBF or CMRO2. However, in the presence of nitrous oxide there was a 25% reduction in blood flow and oxygen consumption."}
{"id": "PMID:29431", "title": "tcPCO2 electrode design, calibration and temperature gradient problems.", "content": "Transcutaneous PCO2 electrodes habe been constructed and evaluated on adults and children. Glass pH and silver reference electrodes were used at 44--45 degrees C, with either circulating water and a copper jacket, or with internal electrical heating. The skin surface PCO2 at 44 degrees C is about 1.33 times PaCO2 plus 3 mmHg when measured with electrodes calibrated in gas at 44 degrees C. Three temperature effects combine in this ratio: Heating raises blood PCO2 4.5%/degrees C, skin metabolism adds about 3 mmHg, and the cooling of the electrode active surface by skin increases electrode reading. Response time to step changes of PaCO2 was about 3 min to 63%, of which 1.2 min was sensor delay, the remainder skin CO2 washout. It was found important to use ethylene glycol-water mixtures rather than water for electrolyte to avoid bubble generation and drift. Heat transfer through the pH glass electrode has been increased by enlarging the internal silver electrode to virtually fill the entire glass electrode. Time required for initial vasodilation and stabilization is similar to that of tcPO2 electrodes, and accuracy of determination of PaCO2 appears to be better than +/- mmHg.", "contents": "tcPCO2 electrode design, calibration and temperature gradient problems. Transcutaneous PCO2 electrodes habe been constructed and evaluated on adults and children. Glass pH and silver reference electrodes were used at 44--45 degrees C, with either circulating water and a copper jacket, or with internal electrical heating. The skin surface PCO2 at 44 degrees C is about 1.33 times PaCO2 plus 3 mmHg when measured with electrodes calibrated in gas at 44 degrees C. Three temperature effects combine in this ratio: Heating raises blood PCO2 4.5%/degrees C, skin metabolism adds about 3 mmHg, and the cooling of the electrode active surface by skin increases electrode reading. Response time to step changes of PaCO2 was about 3 min to 63%, of which 1.2 min was sensor delay, the remainder skin CO2 washout. It was found important to use ethylene glycol-water mixtures rather than water for electrolyte to avoid bubble generation and drift. Heat transfer through the pH glass electrode has been increased by enlarging the internal silver electrode to virtually fill the entire glass electrode. Time required for initial vasodilation and stabilization is similar to that of tcPO2 electrodes, and accuracy of determination of PaCO2 appears to be better than +/- mmHg."}
{"id": "PMID:29432", "title": "Low impedance pH sensitive electrochemical devices that are potentially applicable to transcutaneous PCO2 measurements.", "content": "Two cases of low impedance, non-glass membrane electrodes for pH measurement were evaluated: (I) Metal--metal oxide electrodes and (II) Reduction-oxidation electrodes. The fundamental cause of oxygen sensitivity of metal-metal oxide electrodes were examined and three approaches for its suppression were proposed. For the case of Sb--Sb2Ox electordes, oxygen sensitivity can be attenuated partially by cell loading, either directly across the reference electrode or indirectly across a third slave electrode. In a PO2 range of 8--54 kPa, more than 95% of the PO2  response can be suppressed by loading the cell emf to half of tis open-circuit value. The oxygen sensitivity also was observed to diminished by grinding the metal-metal oxide and pressing it under high pressure into a pellet electrode. Other metal-metal oxide electrodes that have promise in transcutaneous  measurement are the Pd-PdO2 electrodes. The redox electrodes are typified by the Quinhydrone electrode. A membrane Quinhydrome electrode showed a sensitivity of 56 mV/Decade at 37 degree C and no oxygen sensitivity up to 50 kPa and a drift of 1 mV/h over a 24-h period. However, the stability deteriorated over a long-term period.", "contents": "Low impedance pH sensitive electrochemical devices that are potentially applicable to transcutaneous PCO2 measurements. Two cases of low impedance, non-glass membrane electrodes for pH measurement were evaluated: (I) Metal--metal oxide electrodes and (II) Reduction-oxidation electrodes. The fundamental cause of oxygen sensitivity of metal-metal oxide electrodes were examined and three approaches for its suppression were proposed. For the case of Sb--Sb2Ox electordes, oxygen sensitivity can be attenuated partially by cell loading, either directly across the reference electrode or indirectly across a third slave electrode. In a PO2 range of 8--54 kPa, more than 95% of the PO2  response can be suppressed by loading the cell emf to half of tis open-circuit value. The oxygen sensitivity also was observed to diminished by grinding the metal-metal oxide and pressing it under high pressure into a pellet electrode. Other metal-metal oxide electrodes that have promise in transcutaneous  measurement are the Pd-PdO2 electrodes. The redox electrodes are typified by the Quinhydrone electrode. A membrane Quinhydrome electrode showed a sensitivity of 56 mV/Decade at 37 degree C and no oxygen sensitivity up to 50 kPa and a drift of 1 mV/h over a 24-h period. However, the stability deteriorated over a long-term period."}
{"id": "PMID:29437", "title": "The effects of isoproterenol on fetal oxygenation.", "content": "Infusion of isoproterenol (1 microgram/kg/min, i.v.) into the anesthetized pregnant rhesus monkey near term consistently reduced fetal oxygenation, despite diminishing myometrial activity. The decline in pO2 of fetal arterial blood (mean = 4.3 +/- 2.3 mmHg S.D.) was accompanied by an increase in pCO2 tension (mean = 4.6 +/- 2.7 mmHg) and a decline in pH (mean = 0.04 +/- 0.02 S.D.). There was an increase in heart rate and a widening of pulse pressure in the mother and also in the adequately oxygenated fetus providing evidence that the agent crosses the placenta. The poorly oxygenated fetuses developed bradycardia and hypotension. Administration of isoproterenol directly to the fetus elicited similar changes in the composition of blood, and in blood pressure and heart rate, to those observed after administration of the agent to the mother.", "contents": "The effects of isoproterenol on fetal oxygenation. Infusion of isoproterenol (1 microgram/kg/min, i.v.) into the anesthetized pregnant rhesus monkey near term consistently reduced fetal oxygenation, despite diminishing myometrial activity. The decline in pO2 of fetal arterial blood (mean = 4.3 +/- 2.3 mmHg S.D.) was accompanied by an increase in pCO2 tension (mean = 4.6 +/- 2.7 mmHg) and a decline in pH (mean = 0.04 +/- 0.02 S.D.). There was an increase in heart rate and a widening of pulse pressure in the mother and also in the adequately oxygenated fetus providing evidence that the agent crosses the placenta. The poorly oxygenated fetuses developed bradycardia and hypotension. Administration of isoproterenol directly to the fetus elicited similar changes in the composition of blood, and in blood pressure and heart rate, to those observed after administration of the agent to the mother."}
{"id": "PMID:29438", "title": "Glaucoma treatment with timolol.", "content": "Thirty-two eyes from 19 patients with either capsular glaucoma, pigmentary glaucoma or primary open angle glaucoma were given topical timolol and followed through a 3--6 months period. Twelve eyes were previously out of control on full medication including pilocarpine, epinephrine and acetazolamide. Eight of these eyes could be adequately controlled throughout the follow-up period on topical timolol or a combination of timolol and pilocarpine, but without resorting to acetazolamide. One eye needed acetazolamide in combination with timolol, and three eyes had to be referred to surgery. Twelve eyes were adequately controlled either on pilocarpine or full medication, but could be equally well controlled on timolol alone, or timolol and pilocarpine in combination. Acetazolamide could be withheld from all of the six patients who used this drug. Eight eyes were previously untreated. They could all be adequately controlled either on timolol (5 eyes) or timolol and pilocarpine (3 eyes). The study indicates that the effect of timolol 0.5% X 2 may be stronger than the combined effect of epinephrine 1% X 2 and acetazolamide 500 mg a day. Topical timolol was well tolerated. No side reactions occurred and the pupillary size and reactions were not influenced by the timolol treatment.", "contents": "Glaucoma treatment with timolol. Thirty-two eyes from 19 patients with either capsular glaucoma, pigmentary glaucoma or primary open angle glaucoma were given topical timolol and followed through a 3--6 months period. Twelve eyes were previously out of control on full medication including pilocarpine, epinephrine and acetazolamide. Eight of these eyes could be adequately controlled throughout the follow-up period on topical timolol or a combination of timolol and pilocarpine, but without resorting to acetazolamide. One eye needed acetazolamide in combination with timolol, and three eyes had to be referred to surgery. Twelve eyes were adequately controlled either on pilocarpine or full medication, but could be equally well controlled on timolol alone, or timolol and pilocarpine in combination. Acetazolamide could be withheld from all of the six patients who used this drug. Eight eyes were previously untreated. They could all be adequately controlled either on timolol (5 eyes) or timolol and pilocarpine (3 eyes). The study indicates that the effect of timolol 0.5% X 2 may be stronger than the combined effect of epinephrine 1% X 2 and acetazolamide 500 mg a day. Topical timolol was well tolerated. No side reactions occurred and the pupillary size and reactions were not influenced by the timolol treatment."}
{"id": "PMID:29439", "title": "Microcalorimetric study of the effects of cephalexin and cephaloridin on Escherichia coli and Staphylococcus aureus.", "content": "The kinetics of the antibacterial actions of cephalexin and cephaloridin against a strain of Escherichia coli and a strain of Staphylococcus aureus were studied by a flow microcalorimeter. The heat production was related to the number of viable organisms (CFU ml-1), the pH, the optical density of the culture medium (OD540), and the morphology of the antibiotic-exposed bacteria. No heat effects could be registered when the number of CFU was below 10(4) ml-1. The addition of cephalexin, 2.5 microgram ml-1 (5 x MIC), to cultures of S. aureus caused a decrease in the heat production which was only roughly correlated with the number of CFU ml-1. This was also the case when 9.0 microgram ml-1 (2 x MIC) of this drug were added to cultures of E. coli. Two to three hours after the drugs had been added, no heat effects could be registered for the following 6--8 hours, after which an increase in the heat production again occurred. The MIC and MBC of the organisms isolated during this late heat increase were 8--40 times higher than those of the parent test organisms. A direct relation between drug concentration and response, i.e. heat effects produced, was found when increasing concentrations of cephalexin, i.e. 1.0 up to 50 micrograms ml-1 (2--100 x MIC) were added in the logarithmic growth phase to cultures of S. aureus. In ampoule calorimetric experiments, E. coli was cultured in a non-aerated, sealed growth vessel in the presence of cephalexin or cephaloridin in concentrations corresponding to 1/2 x MIC. The thermograms did not differ in shape, although the heat effects occurred somewhat later in the culture containing cephaloridin.", "contents": "Microcalorimetric study of the effects of cephalexin and cephaloridin on Escherichia coli and Staphylococcus aureus. The kinetics of the antibacterial actions of cephalexin and cephaloridin against a strain of Escherichia coli and a strain of Staphylococcus aureus were studied by a flow microcalorimeter. The heat production was related to the number of viable organisms (CFU ml-1), the pH, the optical density of the culture medium (OD540), and the morphology of the antibiotic-exposed bacteria. No heat effects could be registered when the number of CFU was below 10(4) ml-1. The addition of cephalexin, 2.5 microgram ml-1 (5 x MIC), to cultures of S. aureus caused a decrease in the heat production which was only roughly correlated with the number of CFU ml-1. This was also the case when 9.0 microgram ml-1 (2 x MIC) of this drug were added to cultures of E. coli. Two to three hours after the drugs had been added, no heat effects could be registered for the following 6--8 hours, after which an increase in the heat production again occurred. The MIC and MBC of the organisms isolated during this late heat increase were 8--40 times higher than those of the parent test organisms. A direct relation between drug concentration and response, i.e. heat effects produced, was found when increasing concentrations of cephalexin, i.e. 1.0 up to 50 micrograms ml-1 (2--100 x MIC) were added in the logarithmic growth phase to cultures of S. aureus. In ampoule calorimetric experiments, E. coli was cultured in a non-aerated, sealed growth vessel in the presence of cephalexin or cephaloridin in concentrations corresponding to 1/2 x MIC. The thermograms did not differ in shape, although the heat effects occurred somewhat later in the culture containing cephaloridin."}
{"id": "PMID:29440", "title": "Studies on calcium uptake by myometrial microsomes with particular reference to the dependence on inorganic phosphate and oxalate.", "content": "Ca uptake by microsomes isolated from non-pregnant rabbit myometrium was potentiated by both inorganic phosphate (Pi) and oxalate anions. Both Pi and oxalate had little effect on the initial rate of uptake but a pronounced effect on the capacity of Ca uptake measured after 20 min which was greater in the presence of oxalate than that of Pi (5 mM each). The presence or absence of sucrose in the uptake medium had a significant effect on oxalate-induced potentiation of Ca uptake but not on that potentiated by Pi or that measured in the absence of either potentiating anion. A part of Ca accumulated additionally under the influence of sucrose could be removed by washing microsomes with KCl. Another significant difference between the pontentiating effect of oxalate and Pi was observed when the pH of the incubation medium was varied. In the presence of oxalate the pH optimum was between 6.4--6.8, whereas that in its absence or in the presence of Pi the optimal pH was around 7.2. Reduction in pH from 7.2 to 6.8 along with the substitution of KCl by sucrose resulted in 3-fold increase in Ca uptake when oxalate was used as the potentiating anion. The results suggest that Ca is taken up by a different mechanism in the presence of oxalate than that in its absence or when oxalate anion is substituted with inorganic phosphate.", "contents": "Studies on calcium uptake by myometrial microsomes with particular reference to the dependence on inorganic phosphate and oxalate. Ca uptake by microsomes isolated from non-pregnant rabbit myometrium was potentiated by both inorganic phosphate (Pi) and oxalate anions. Both Pi and oxalate had little effect on the initial rate of uptake but a pronounced effect on the capacity of Ca uptake measured after 20 min which was greater in the presence of oxalate than that of Pi (5 mM each). The presence or absence of sucrose in the uptake medium had a significant effect on oxalate-induced potentiation of Ca uptake but not on that potentiated by Pi or that measured in the absence of either potentiating anion. A part of Ca accumulated additionally under the influence of sucrose could be removed by washing microsomes with KCl. Another significant difference between the pontentiating effect of oxalate and Pi was observed when the pH of the incubation medium was varied. In the presence of oxalate the pH optimum was between 6.4--6.8, whereas that in its absence or in the presence of Pi the optimal pH was around 7.2. Reduction in pH from 7.2 to 6.8 along with the substitution of KCl by sucrose resulted in 3-fold increase in Ca uptake when oxalate was used as the potentiating anion. The results suggest that Ca is taken up by a different mechanism in the presence of oxalate than that in its absence or when oxalate anion is substituted with inorganic phosphate."}
{"id": "PMID:29441", "title": "A controlled long-term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects.", "content": "The hypnotic effect of flunitrazepam (Ro 5-4200), nitrazepam and a placebo was studied in 117 outpatients using hypnotics for at least 3 months prior to the study. They obtained various neurotropic drugs and this and other treatments were unchanged throughout the trial period of 13 weeks. This consisted of 3 weeks on the previously used hypnotic, 3 weeks on a test drug (during the first of these a doubling of the dose was permitted if the initial dose of 1 mg flunitrazepam, 5 mg nitrazepam or one tablet of placebo was not satisfactory) and 4 weeks' observation after a request to stop medication with the test drug. The effects were evaluated every week by self-ratings. Also noted were: the frequency of dose increase after 1 week of the test period, number of drop-outs in the test period, and failure in the attempt to stop taking the test drug. A \"psychological concentration test\" was done, as was a follow-up interview. The self-ratings had a good reliability and showed that more patients experienced shorter sleep induction, longer sleep time, better sleep quality and a subjective feeling of having had a better rest with flunitrazepam than with either nitrazepam or placebo. There were no differences between the nitrazepam and the placebo groups. Tiredness was the most common side effect and appeared in the same frequency in all groups. The number of patients who increased the dose after 1 week's medication, as well as the number of drop-outs, was significantly higher in the nitrazepam and placebo groups than in the flunitrazepam group. There was no difference in the ability to discontinue the medication between the test groups or between groups having previously used different hypnotics. The \"psychological concentration test\" did not reveal any differences between groups. It was concluded that withdrawal of a hypnotic in chronic users was not facilitated by the use of a placebo. This was interpreted as due to a strong psychological dependence upon the hypnotics and their lack of pharmacological effects during long-term treatment.", "contents": "A controlled long-term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects. The hypnotic effect of flunitrazepam (Ro 5-4200), nitrazepam and a placebo was studied in 117 outpatients using hypnotics for at least 3 months prior to the study. They obtained various neurotropic drugs and this and other treatments were unchanged throughout the trial period of 13 weeks. This consisted of 3 weeks on the previously used hypnotic, 3 weeks on a test drug (during the first of these a doubling of the dose was permitted if the initial dose of 1 mg flunitrazepam, 5 mg nitrazepam or one tablet of placebo was not satisfactory) and 4 weeks' observation after a request to stop medication with the test drug. The effects were evaluated every week by self-ratings. Also noted were: the frequency of dose increase after 1 week of the test period, number of drop-outs in the test period, and failure in the attempt to stop taking the test drug. A \"psychological concentration test\" was done, as was a follow-up interview. The self-ratings had a good reliability and showed that more patients experienced shorter sleep induction, longer sleep time, better sleep quality and a subjective feeling of having had a better rest with flunitrazepam than with either nitrazepam or placebo. There were no differences between the nitrazepam and the placebo groups. Tiredness was the most common side effect and appeared in the same frequency in all groups. The number of patients who increased the dose after 1 week's medication, as well as the number of drop-outs, was significantly higher in the nitrazepam and placebo groups than in the flunitrazepam group. There was no difference in the ability to discontinue the medication between the test groups or between groups having previously used different hypnotics. The \"psychological concentration test\" did not reveal any differences between groups. It was concluded that withdrawal of a hypnotic in chronic users was not facilitated by the use of a placebo. This was interpreted as due to a strong psychological dependence upon the hypnotics and their lack of pharmacological effects during long-term treatment."}
{"id": "PMID:29442", "title": "Demonstration of enzymatic activity converting azathioprine to 6-mercaptopurine.", "content": "The enzymatic conversion of azathioprine to 6-mercaptopurine was detected at pH 6.5 with rat liver supernatants, although the non-enzymatic reaction predominated at pH 7.0 and 7.5. Glutathione S-transferase may catalize this conversion. Activities of the enzyme in liver with both zathioprine and 1,2-dichloro-4-nitrobenzene as substrate decreased upon carbon tetrachloride-induced hepatic injury. These results may explain an ineffectiveness of azathioprine in patients with severe hepatic damage.", "contents": "Demonstration of enzymatic activity converting azathioprine to 6-mercaptopurine. The enzymatic conversion of azathioprine to 6-mercaptopurine was detected at pH 6.5 with rat liver supernatants, although the non-enzymatic reaction predominated at pH 7.0 and 7.5. Glutathione S-transferase may catalize this conversion. Activities of the enzyme in liver with both zathioprine and 1,2-dichloro-4-nitrobenzene as substrate decreased upon carbon tetrachloride-induced hepatic injury. These results may explain an ineffectiveness of azathioprine in patients with severe hepatic damage."}
{"id": "PMID:29447", "title": "Transmitters for the afferent and efferent systems of the neostriatum and their possible interactions.", "content": "The surgical denervation techniques have been widely employed as a tool to identify the neuronal origin of various neurotransmitters in the basal ganglia. Besides the well known nigrostriatal dopaminergic pathway, there is a high glutamic acid-containing corticostriatal connection and the cholinergic thalamostriatal projection. On the other hand, it is strongly suggested that GABA is the transmitter for the strionigral and striopallidal efferent systems. Furthermore, no evidence was found to support strionigral or striopallidal cholinergic pathways. From the 6-OHDA experiments, it is proposed that the 6-OHDA not only has a selective toxic effect on dopaminergic neurons, but also affects the cholinergic neurons in the striatum, and may provide further evidence for dopaminergic-cholinergic interaction in the striatum. Finally, GABA may modulate dopamine metabolism in the striatum.", "contents": "Transmitters for the afferent and efferent systems of the neostriatum and their possible interactions. The surgical denervation techniques have been widely employed as a tool to identify the neuronal origin of various neurotransmitters in the basal ganglia. Besides the well known nigrostriatal dopaminergic pathway, there is a high glutamic acid-containing corticostriatal connection and the cholinergic thalamostriatal projection. On the other hand, it is strongly suggested that GABA is the transmitter for the strionigral and striopallidal efferent systems. Furthermore, no evidence was found to support strionigral or striopallidal cholinergic pathways. From the 6-OHDA experiments, it is proposed that the 6-OHDA not only has a selective toxic effect on dopaminergic neurons, but also affects the cholinergic neurons in the striatum, and may provide further evidence for dopaminergic-cholinergic interaction in the striatum. Finally, GABA may modulate dopamine metabolism in the striatum."}
{"id": "PMID:29455", "title": "Enzymic studies on glial and neuronal cells during myelination.", "content": "The formation of ethanolamine plasmalogen from labelled 1-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine was studied in neurons and glial cells of the developing rat brain. It was found that the conversion of the ether to the enol-ether bond of the 1-alkyl moiety by the neuronal and glial desaturase system requires unsaturated fatty acids at the 2 position of the substrate. There is almost no difference between the activity of the neuronal and glial desaturase during the period of active myelination, whereas the neuronal cell fraction of the adult rats displays a threefold higher enzyme activity as compared to the glial cells. Evidence for the involvement of a microsomal electron transport system in the enzymic conversion of alkylacyl-glycero-3-phosphorylethanolamine to ethanolamine plasmalogen was obtained by using specific antibodies against NADH-cytochrome b5 reductase. Cytochrome b5 stimulated the biosynthesis of ethanolamine plasmalogen.", "contents": "Enzymic studies on glial and neuronal cells during myelination. The formation of ethanolamine plasmalogen from labelled 1-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine was studied in neurons and glial cells of the developing rat brain. It was found that the conversion of the ether to the enol-ether bond of the 1-alkyl moiety by the neuronal and glial desaturase system requires unsaturated fatty acids at the 2 position of the substrate. There is almost no difference between the activity of the neuronal and glial desaturase during the period of active myelination, whereas the neuronal cell fraction of the adult rats displays a threefold higher enzyme activity as compared to the glial cells. Evidence for the involvement of a microsomal electron transport system in the enzymic conversion of alkylacyl-glycero-3-phosphorylethanolamine to ethanolamine plasmalogen was obtained by using specific antibodies against NADH-cytochrome b5 reductase. Cytochrome b5 stimulated the biosynthesis of ethanolamine plasmalogen."}
{"id": "PMID:29457", "title": "Interaction between PCO2 and plasma [HCO-3] in regulation of CSF [HCO-3] in respiratory alkalosis and metabolic acidosis.", "content": "The results of studies presented may be interpreted in light of the dual contribution theory of regulation of CSF acid-base balance, indicating significant interaction between systemic and local CNS mechanisms in H+ homeostasis in the brain and CSF. Both systemic and local mechanisms are at work in H+ homeostasis in the brain and CSF and depending on the specific acid-base disorder or the duration of the imbalance one or the other of the two factors may be the dominant one in maintaining H+ levels in the \"normal\" range. These factors come into play only when there has been a change in central pH with the primary aim of bringing the CNS [H+] towards normal.", "contents": "Interaction between PCO2 and plasma [HCO-3] in regulation of CSF [HCO-3] in respiratory alkalosis and metabolic acidosis. The results of studies presented may be interpreted in light of the dual contribution theory of regulation of CSF acid-base balance, indicating significant interaction between systemic and local CNS mechanisms in H+ homeostasis in the brain and CSF. Both systemic and local mechanisms are at work in H+ homeostasis in the brain and CSF and depending on the specific acid-base disorder or the duration of the imbalance one or the other of the two factors may be the dominant one in maintaining H+ levels in the \"normal\" range. These factors come into play only when there has been a change in central pH with the primary aim of bringing the CNS [H+] towards normal."}
{"id": "PMID:29464", "title": "Conditions for production of thermosensitive attenuated influenza virus recombinants.", "content": "Recombination and cross-reactivation between virulent influenza viruses and a cold-adapted thermosensitive vaccine strain regularly produced genetically stable attenuated recombinants, the selection of which was based on the thermosensitivity marker. This marker, correlating with the safety of the recombinants for man was inherited independently on the properties of the haemagglutinin and neuraminidase surface antigens. There was no relationship between the thermosensitivity of the resulting recombinants and the decrease in the optimal temperature of the neuraminidase activity (OTNA marker). This indicates a separate localization in the viral genome of the mutation damages responsible for the expression of ts and OTNA markers.", "contents": "Conditions for production of thermosensitive attenuated influenza virus recombinants. Recombination and cross-reactivation between virulent influenza viruses and a cold-adapted thermosensitive vaccine strain regularly produced genetically stable attenuated recombinants, the selection of which was based on the thermosensitivity marker. This marker, correlating with the safety of the recombinants for man was inherited independently on the properties of the haemagglutinin and neuraminidase surface antigens. There was no relationship between the thermosensitivity of the resulting recombinants and the decrease in the optimal temperature of the neuraminidase activity (OTNA marker). This indicates a separate localization in the viral genome of the mutation damages responsible for the expression of ts and OTNA markers."}
{"id": "PMID:29465", "title": "Interspecies interactions of arboviruses. III. Competition for virus envelope antigens in mixed Getah and Sindbis virus populations.", "content": "Interactions of Getah and Sindbis virus populations in mixed infections of 5 tissue systems were competitive or neutral. The type of interaction is regulated by the host cell and virus population density. On reproduction in mouse brains and SPEV cell cultures the mixed population exhibited antigenic markers of Getah virus; in Syrian hamster kidney and chick embryo cell cultures those of Sindbis virus; and in Chinese hamster kidney cell cultures the antigenic markers of both viruses. Mixed populations with monospecific antigenic characteristics contained genomes of both viruses detectable by the TC marker (dual spetrum of cytopathogenicity). Clonal analysis of such populations confirmed the occurrence of genome masking and demonstrated the formation of genotypically mixed particles. Possible mechanisms of the antigenic dominance of one virus and selective blocking of functions of the other virus are discussed.", "contents": "Interspecies interactions of arboviruses. III. Competition for virus envelope antigens in mixed Getah and Sindbis virus populations. Interactions of Getah and Sindbis virus populations in mixed infections of 5 tissue systems were competitive or neutral. The type of interaction is regulated by the host cell and virus population density. On reproduction in mouse brains and SPEV cell cultures the mixed population exhibited antigenic markers of Getah virus; in Syrian hamster kidney and chick embryo cell cultures those of Sindbis virus; and in Chinese hamster kidney cell cultures the antigenic markers of both viruses. Mixed populations with monospecific antigenic characteristics contained genomes of both viruses detectable by the TC marker (dual spetrum of cytopathogenicity). Clonal analysis of such populations confirmed the occurrence of genome masking and demonstrated the formation of genotypically mixed particles. Possible mechanisms of the antigenic dominance of one virus and selective blocking of functions of the other virus are discussed."}
{"id": "PMID:29466", "title": "Experimental pathogenesis of non-lethal herpesvirus infection and the establishment of latency.", "content": "In rabbits inoculated into the right scarified cornea with the Kupka strain of human Herpesvirus type 1 (HHV 1), healing of the keratitis occurred between days 8--12 post infection (p.i.). Viral particles were seen in nuclei and cytoplasm of corneal epithelium cells and in a few fibrocytes of corneal stroma. By immunofluorescence and electron microscopy, the virus was demonstrated in single neurons and satellite cells of the homolateral Gasserian ganglion since 24 hr p.i. From 20 hr to 8 days p.i., HHV 1 was found in ganglia of 7 out of 15 rabbits, while the explantation was positive in 10 out of 12 animals. In the course of latency, single HHV antigen-containing cells were seen in ganglia of 3 out of 7 rabbits and virus isolation attempts before explantation always were negative. Viral antigen was found in single ganglion cells only in 20% of rabbits with healed corneal lesions while the explanation of the ganglion tissue yielded HHV at an unchanged high frequency (92% of animals).", "contents": "Experimental pathogenesis of non-lethal herpesvirus infection and the establishment of latency. In rabbits inoculated into the right scarified cornea with the Kupka strain of human Herpesvirus type 1 (HHV 1), healing of the keratitis occurred between days 8--12 post infection (p.i.). Viral particles were seen in nuclei and cytoplasm of corneal epithelium cells and in a few fibrocytes of corneal stroma. By immunofluorescence and electron microscopy, the virus was demonstrated in single neurons and satellite cells of the homolateral Gasserian ganglion since 24 hr p.i. From 20 hr to 8 days p.i., HHV 1 was found in ganglia of 7 out of 15 rabbits, while the explantation was positive in 10 out of 12 animals. In the course of latency, single HHV antigen-containing cells were seen in ganglia of 3 out of 7 rabbits and virus isolation attempts before explantation always were negative. Viral antigen was found in single ganglion cells only in 20% of rabbits with healed corneal lesions while the explanation of the ganglion tissue yielded HHV at an unchanged high frequency (92% of animals)."}
{"id": "PMID:29467", "title": "Antiviral activity of dipyridamole derivatives.", "content": "Among 46 novel pyrimido [5.4-d] pyrimidine derivatives, 26 compounds were found to exhibit antiviral activity as revealed in a test programme against Mengo, Coxsackie B1, fowl plague, vaccinia and pseudorabies viruses, as concerns inhibition of plaque formation and of infectious virus yield. Attempts to disclose structure-activity relationships by discriminant analysis pointed to a possible importance of hydrophobic substitution for the antiviral effectiveness against Mengo virus of the derivatives investigated.", "contents": "Antiviral activity of dipyridamole derivatives. Among 46 novel pyrimido [5.4-d] pyrimidine derivatives, 26 compounds were found to exhibit antiviral activity as revealed in a test programme against Mengo, Coxsackie B1, fowl plague, vaccinia and pseudorabies viruses, as concerns inhibition of plaque formation and of infectious virus yield. Attempts to disclose structure-activity relationships by discriminant analysis pointed to a possible importance of hydrophobic substitution for the antiviral effectiveness against Mengo virus of the derivatives investigated."}
{"id": "PMID:29468", "title": "Isolation of influenza virus from wild ducks (Anas platyrhynchos).", "content": "In the course of studies on influenza virus ecology, Influenzavirus A was isolated from a cloacal smear from a wild duck (Anas platyrhynchos) caught in west Slovakia. The strain was identified as A(Hav7Nav1). The results of virus isolation experiments from other species of aquatic and other small birds were negative.", "contents": "Isolation of influenza virus from wild ducks (Anas platyrhynchos). In the course of studies on influenza virus ecology, Influenzavirus A was isolated from a cloacal smear from a wild duck (Anas platyrhynchos) caught in west Slovakia. The strain was identified as A(Hav7Nav1). The results of virus isolation experiments from other species of aquatic and other small birds were negative."}
{"id": "PMID:29469", "title": "Influence of mild acid hydrolysis on the antigenic properties of phase I Coxiella burnetii.", "content": "Mild acid hydrolysis of phase I Coxiella burnetii cells gradually cleaved off polysaccharide chains, which contain determinants of antigen 1, thus unmasking determinants of the diagnostically important antigen 2. This artificial phase I to phase II conversion was reflected by changed serological activity in the complement-fixation (CF) test and by changed nonspecific phagocytosis. The product of mild acid hydrolysis can serve as a complex diagnostic preparation, because it reacts in the CF test with antibodies directed to both C. burnetii antigens.", "contents": "Influence of mild acid hydrolysis on the antigenic properties of phase I Coxiella burnetii. Mild acid hydrolysis of phase I Coxiella burnetii cells gradually cleaved off polysaccharide chains, which contain determinants of antigen 1, thus unmasking determinants of the diagnostically important antigen 2. This artificial phase I to phase II conversion was reflected by changed serological activity in the complement-fixation (CF) test and by changed nonspecific phagocytosis. The product of mild acid hydrolysis can serve as a complex diagnostic preparation, because it reacts in the CF test with antibodies directed to both C. burnetii antigens."}
{"id": "PMID:29470", "title": "Immunological properties of the lipopolysaccharide-protein complex of Coxiella burnetii.", "content": "Purified lipopolysaccharide-protein complex (LPS-PC) extracted by trichloroacetic acid from phase I Coxiella burnetii organisms induced in mice and rabbits fair levels of antibodies directed to antigen 1 and antigen 2, as detected by complement-fixation (CF), microagglutination (MA), opsonization-phagocytosis (OP) and serum protection (SP) tests. In guinea pigs only very low levels of MA antibodies against antigen 2 were demonstrated. In rabbit serum, MA antibodies directed to antigen 2 were found exclusively in the IgM fraction after the primary immunizing dose; the second dose was followed by gradual shift of MA antibodies to the IgG class. Two immunizing doses of the LPS-PC were more effective when testing antibody response in mice or protection of mice and guinea pigs against phase I virulent challenge.", "contents": "Immunological properties of the lipopolysaccharide-protein complex of Coxiella burnetii. Purified lipopolysaccharide-protein complex (LPS-PC) extracted by trichloroacetic acid from phase I Coxiella burnetii organisms induced in mice and rabbits fair levels of antibodies directed to antigen 1 and antigen 2, as detected by complement-fixation (CF), microagglutination (MA), opsonization-phagocytosis (OP) and serum protection (SP) tests. In guinea pigs only very low levels of MA antibodies against antigen 2 were demonstrated. In rabbit serum, MA antibodies directed to antigen 2 were found exclusively in the IgM fraction after the primary immunizing dose; the second dose was followed by gradual shift of MA antibodies to the IgG class. Two immunizing doses of the LPS-PC were more effective when testing antibody response in mice or protection of mice and guinea pigs against phase I virulent challenge."}
{"id": "PMID:29471", "title": "Cytomegalovirus infections in the human population.", "content": "Diagnostic and clinical experience gained in the period from 1966--1977 is summarized. Cytomegalovirus was isolated from 35 sucklings and 5 infants aged more than 1 year as well as from necropsy materials from 10 sucklings. The most frequently involved were the respiratory tract (77.8%), liver (53.5%) and haematopoetic apparatus (42.2%). Congenital defects were found in 22.2%. The incidence in the population varied from 20% in sucklings to 50--60% in persons aged over 40 years. The incidence of infection was higher in sucklings and infants in nurseries. Out of 37 adult patients with kidney transplantation, the virus was isolated from 10 (27%) and complement-fixing antibodies were found in 34 (91%) patients.", "contents": "Cytomegalovirus infections in the human population. Diagnostic and clinical experience gained in the period from 1966--1977 is summarized. Cytomegalovirus was isolated from 35 sucklings and 5 infants aged more than 1 year as well as from necropsy materials from 10 sucklings. The most frequently involved were the respiratory tract (77.8%), liver (53.5%) and haematopoetic apparatus (42.2%). Congenital defects were found in 22.2%. The incidence in the population varied from 20% in sucklings to 50--60% in persons aged over 40 years. The incidence of infection was higher in sucklings and infants in nurseries. Out of 37 adult patients with kidney transplantation, the virus was isolated from 10 (27%) and complement-fixing antibodies were found in 34 (91%) patients."}
{"id": "PMID:29472", "title": "Strain differences in electrophoretic mobility of influenzavirus A polypeptides.", "content": "Slab polyacrylamide gel electrophoresis of Influenza-virus A strains varying in antigenic composition of the envelope and in the natural host species showed the nucleprotein and membrane proteins to have a standard molecular weight of 58,000 and 24,000 daltons, respectively. The electrophoretic mobility and molecular weights of the light and heavy chains of haemagglutinin varied in the strains under study. The differences observed persisted on passaging and were transferred upon genome recombination.", "contents": "Strain differences in electrophoretic mobility of influenzavirus A polypeptides. Slab polyacrylamide gel electrophoresis of Influenza-virus A strains varying in antigenic composition of the envelope and in the natural host species showed the nucleprotein and membrane proteins to have a standard molecular weight of 58,000 and 24,000 daltons, respectively. The electrophoretic mobility and molecular weights of the light and heavy chains of haemagglutinin varied in the strains under study. The differences observed persisted on passaging and were transferred upon genome recombination."}
{"id": "PMID:29473", "title": "Isolation of encephalomyocarditis virus from the pheasant (Phasianus colchicus) in Czechoslovakia.", "content": "The first isolation of encephalomyocarditis (EMC) virus from the blood and brain of a pheasant (Phasianus colchicus) captured in Moravia is reported. Complement-fixation (CF) tests with reference antisera revealed no relationship to any of a wide range of known arboviruses.", "contents": "Isolation of encephalomyocarditis virus from the pheasant (Phasianus colchicus) in Czechoslovakia. The first isolation of encephalomyocarditis (EMC) virus from the blood and brain of a pheasant (Phasianus colchicus) captured in Moravia is reported. Complement-fixation (CF) tests with reference antisera revealed no relationship to any of a wide range of known arboviruses."}
{"id": "PMID:29474", "title": "Sensitivity of formation of adenovirus specific tumour antigen to leukocyte interferon.", "content": "The effect of various concentrations of chicken leukocyte interferon was examined on the expression of adenovirus tumour (T) antigen in chick embryo cells. The inhibition of T antigen formation was dependent on the multiplicity of infection. The reduction of T antigen-producing cells was greater when interferon was applied before and after virus infection.", "contents": "Sensitivity of formation of adenovirus specific tumour antigen to leukocyte interferon. The effect of various concentrations of chicken leukocyte interferon was examined on the expression of adenovirus tumour (T) antigen in chick embryo cells. The inhibition of T antigen formation was dependent on the multiplicity of infection. The reduction of T antigen-producing cells was greater when interferon was applied before and after virus infection."}
{"id": "PMID:29475", "title": "Rates of infection in, and transmission of, African horse-sickness virus by Aedes aegypti mosquitoes.", "content": "Very low infection rates (less than 3%) were obtained when Aedes aegypti mosquitoes ingested blood contained 5.8--6.5 log10 MLD50/0.02 ml African horse sickness virus (AHSV). When A. aegypti mosquitoes were inoculated intrathoracically with virus, however, high infection rates were achieved. Mosquitoes infected by inoculum failed to transmit virus to embryonated hens eggs by bite, and virus could not be detected in membrane or blood when inoculated mosquitoes were allowed to engorge on uninfected blood through a chick skin membrane. It was concluded that the mosquito A. aegypti is unlikely to be an effective vector of AHSV.", "contents": "Rates of infection in, and transmission of, African horse-sickness virus by Aedes aegypti mosquitoes. Very low infection rates (less than 3%) were obtained when Aedes aegypti mosquitoes ingested blood contained 5.8--6.5 log10 MLD50/0.02 ml African horse sickness virus (AHSV). When A. aegypti mosquitoes were inoculated intrathoracically with virus, however, high infection rates were achieved. Mosquitoes infected by inoculum failed to transmit virus to embryonated hens eggs by bite, and virus could not be detected in membrane or blood when inoculated mosquitoes were allowed to engorge on uninfected blood through a chick skin membrane. It was concluded that the mosquito A. aegypti is unlikely to be an effective vector of AHSV."}
{"id": "PMID:29476", "title": "Rickettsiella phytoseiuli and virus-like particles in Phytosfiulus persimilis (Gamasoidea: Phytoseiidae) mites.", "content": "Electron microscope investigation of tissue of Phytoseiulus persimilis mites revealed its double infection with Rickettsiella phytoseiuli and virus-like particles. The presence of rickettsiae in tissues of the mite seemed to be decisive for establishment of virus infection.", "contents": "Rickettsiella phytoseiuli and virus-like particles in Phytosfiulus persimilis (Gamasoidea: Phytoseiidae) mites. Electron microscope investigation of tissue of Phytoseiulus persimilis mites revealed its double infection with Rickettsiella phytoseiuli and virus-like particles. The presence of rickettsiae in tissues of the mite seemed to be decisive for establishment of virus infection."}
{"id": "PMID:29477", "title": "Cross reactions among flaviviruses in macrophage migration inhibition assay.", "content": "Adult Swiss albino mice were immunized intravenously with flaviviviruses. Cellular immune response was studied by macrophage migration inhibition assay. Migration of cells from sensitized mice was significantly inhibited in the presence of homologous virus or antigen. Migration inhibition was also significant with serologically related viruses, thus establishing cross reaction in cellular immune response.", "contents": "Cross reactions among flaviviruses in macrophage migration inhibition assay. Adult Swiss albino mice were immunized intravenously with flaviviviruses. Cellular immune response was studied by macrophage migration inhibition assay. Migration of cells from sensitized mice was significantly inhibited in the presence of homologous virus or antigen. Migration inhibition was also significant with serologically related viruses, thus establishing cross reaction in cellular immune response."}
{"id": "PMID:29480", "title": "Methodical aspects of the experimental chemotherapy of viral infections.", "content": "An analysis of the methods of testing the antiviral activity in vitro (in cell cultures) and in vivo (in experimental virus infections) is presented. The necessity of applying two-stage screening in vitro is emphasized. The chemotherapeutic viral models is in vitro testing as well as the principles of modelling of experimental viral infections are examined. Criteria for stage-by-stage assessment of the antiviral activity of the substances tested are formulated.", "contents": "Methodical aspects of the experimental chemotherapy of viral infections. An analysis of the methods of testing the antiviral activity in vitro (in cell cultures) and in vivo (in experimental virus infections) is presented. The necessity of applying two-stage screening in vitro is emphasized. The chemotherapeutic viral models is in vitro testing as well as the principles of modelling of experimental viral infections are examined. Criteria for stage-by-stage assessment of the antiviral activity of the substances tested are formulated."}
{"id": "PMID:29481", "title": "The theoretical implications of chlorpromazine as a sensory integrative theory.", "content": "In order to evaluate the influence of antipsychotic drugs used in the treatment of schizophrenia on therapy based on sensory integrative theory, this study, developed through library research, explores the theoretical bases for these two modes of treatment. Studies of chlorpromazine, a prototypical antipsychotic drug, show that its local action on the neurotransmitters of the brain may explain in theory its therapeutic efficacy. By citing evidence of sensory processing deficits in schizophrenic patients, a theoretical basis for the use of a sensory integrative approach to therapy is established. A comparison of these theories leads to the conclusion that a sensory integrative approach can serve as an important reinforcer of the therapeutic actions of chlorpromazine. Implications for treatment and research are considered.", "contents": "The theoretical implications of chlorpromazine as a sensory integrative theory. In order to evaluate the influence of antipsychotic drugs used in the treatment of schizophrenia on therapy based on sensory integrative theory, this study, developed through library research, explores the theoretical bases for these two modes of treatment. Studies of chlorpromazine, a prototypical antipsychotic drug, show that its local action on the neurotransmitters of the brain may explain in theory its therapeutic efficacy. By citing evidence of sensory processing deficits in schizophrenic patients, a theoretical basis for the use of a sensory integrative approach to therapy is established. A comparison of these theories leads to the conclusion that a sensory integrative approach can serve as an important reinforcer of the therapeutic actions of chlorpromazine. Implications for treatment and research are considered."}
{"id": "PMID:29482", "title": "Arterial hypoxemia following the administration of sublingual nitroglycerin.", "content": "The effect of nitroglycerin on arterial blood gases and cardiovascular hemodynamics were studied in patients with coronary artery disease. In 13 premedicated patients blood gases and cardiovascular hemodynamics were studied before and 10 minutes after sublingual nitroglycerin (0.6 mg). In eight unpremedicated patients only blood gases were determined before and 10 minutes after sublingual nitroglycerin 0.6 mg. All studies were performed before induction of anesthesia with the patients in the supine position breathing room air. In both groups, arterial PO2 decreased significantly (p less than 0.001); pH and pCO2 did not change. In the 13 patients on which hemodynamic studies were performed, the mean arterial pressure  (p less than 0.001), cardiac index (p less than 0.001), central venous pressure (p less than 0.001), pulmonary artery (p less than 0.001) and pulmonary artery wedge pressure (p less than 0.001) decreased. Calculated values for systemic and pulmonary vascular resistance were not significantly altered (p greater than 0.4). This study gives conclusive evidence that nitroglycerin reduces arterial PO2 in most patients with coronary artery disease breathing room air in the supine position. The possible mechanisms and clinical implications are discussed.", "contents": "Arterial hypoxemia following the administration of sublingual nitroglycerin. The effect of nitroglycerin on arterial blood gases and cardiovascular hemodynamics were studied in patients with coronary artery disease. In 13 premedicated patients blood gases and cardiovascular hemodynamics were studied before and 10 minutes after sublingual nitroglycerin (0.6 mg). In eight unpremedicated patients only blood gases were determined before and 10 minutes after sublingual nitroglycerin 0.6 mg. All studies were performed before induction of anesthesia with the patients in the supine position breathing room air. In both groups, arterial PO2 decreased significantly (p less than 0.001); pH and pCO2 did not change. In the 13 patients on which hemodynamic studies were performed, the mean arterial pressure  (p less than 0.001), cardiac index (p less than 0.001), central venous pressure (p less than 0.001), pulmonary artery (p less than 0.001) and pulmonary artery wedge pressure (p less than 0.001) decreased. Calculated values for systemic and pulmonary vascular resistance were not significantly altered (p greater than 0.4). This study gives conclusive evidence that nitroglycerin reduces arterial PO2 in most patients with coronary artery disease breathing room air in the supine position. The possible mechanisms and clinical implications are discussed."}
{"id": "PMID:29483", "title": "Evaluation of the counterimmunoelectrophoretic (CIE) procedure in a clinical laboratory setting.", "content": "The counterimmunoelectrophoretic (CIE) procedure was evaluated under clinical laboratory conditions to determine its validity and comparability with culture methods. The procedure was further evaluated to determine applicability to a variety of clinical samples. An inexpensive set-up was developed to utilize the CIE procedure at bench level. Results indicated the procedure to be sensitive in detecting Haemophilus influenzae, type b, and Neisseria meningitidis (meningococcus), group B. The procedure was more sensitive for detection of H. influenzae, type b, than for meningococcus, group B. The authors have confirmed the usefulness of the CIE procedure in the detection of group B streptococci, pneumococci and teichoic acid antibody to Staphylococcus aureus. Detection of Escherichia coli K 1 antigen was also accomplished by CIE. In the authors' laboratory the CIE procedure was superior to culture methods when used for the detection of H. influenzae, type b, and meningococcus group B.", "contents": "Evaluation of the counterimmunoelectrophoretic (CIE) procedure in a clinical laboratory setting. The counterimmunoelectrophoretic (CIE) procedure was evaluated under clinical laboratory conditions to determine its validity and comparability with culture methods. The procedure was further evaluated to determine applicability to a variety of clinical samples. An inexpensive set-up was developed to utilize the CIE procedure at bench level. Results indicated the procedure to be sensitive in detecting Haemophilus influenzae, type b, and Neisseria meningitidis (meningococcus), group B. The procedure was more sensitive for detection of H. influenzae, type b, than for meningococcus, group B. The authors have confirmed the usefulness of the CIE procedure in the detection of group B streptococci, pneumococci and teichoic acid antibody to Staphylococcus aureus. Detection of Escherichia coli K 1 antigen was also accomplished by CIE. In the authors' laboratory the CIE procedure was superior to culture methods when used for the detection of H. influenzae, type b, and meningococcus group B."}
{"id": "PMID:29485", "title": "Analysis of hydroxyzine hydrochloride, meperidine hydrochloride and atropine sulfate in glass and plastic syringes.", "content": "The apparent stability of combinations of hydroxyzine hydrochloride and meperidine hydrochloride (50 mg/2 ml each) and of these two drugs (50 mg/2.5 ml each) and atropine sulfate (0.4 mg/2.5 ml) in prefilled glass and plastic syringes was studied. Syringes (3 ml) containing the combinations were stored at 25 C and 3 C for 10 days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined in addition to visual inspection. Results of these qualitative tests indicated that the mixtures apparently were stable for 10 days at room temperature or when refrigerated. No differences were found between solutions stored in glass and those stored in plastic syringes. Degradation of the syringe contents or appearance of additional constituents was not detected in any of the admixtures, and they were considered to be chemically compatible within the limitations of the study. The study suggests that storage of these combinations in syringes is feasible but the results cannot be extrapolated to drug solutions or syringes other than those studied.", "contents": "Analysis of hydroxyzine hydrochloride, meperidine hydrochloride and atropine sulfate in glass and plastic syringes. The apparent stability of combinations of hydroxyzine hydrochloride and meperidine hydrochloride (50 mg/2 ml each) and of these two drugs (50 mg/2.5 ml each) and atropine sulfate (0.4 mg/2.5 ml) in prefilled glass and plastic syringes was studied. Syringes (3 ml) containing the combinations were stored at 25 C and 3 C for 10 days and analyzed at specific time intervals. Absorption spectra, chromatographic characteristics and pH were determined in addition to visual inspection. Results of these qualitative tests indicated that the mixtures apparently were stable for 10 days at room temperature or when refrigerated. No differences were found between solutions stored in glass and those stored in plastic syringes. Degradation of the syringe contents or appearance of additional constituents was not detected in any of the admixtures, and they were considered to be chemically compatible within the limitations of the study. The study suggests that storage of these combinations in syringes is feasible but the results cannot be extrapolated to drug solutions or syringes other than those studied."}
{"id": "PMID:29487", "title": "Education and integration of midlevel health-care practitioners in obstetrics and gynecology: experience of a training program in Washington state.", "content": "The impetus for the development of the Gynecorps Training Program was the identification of medically underserved populations of women in Washington State and their need for preventive health care, the maldistribution of physicians, and the success of a pilot program for training midlevel personnel conducted in 1972 by the Department of Obstetrics and Gynecology, University of Washington School of Medicine. The program trains community-based and -sponsored Registered Nurses and Physician's Assistants as women's health-care specialists, with the goal of delivering preventive care in obstetrics and gynecology to populations of high-risk, low-income, and/or underserved women. A summary of the training program, its curriculum, and the integration of its graduates into community health teams is presented and discussed.", "contents": "Education and integration of midlevel health-care practitioners in obstetrics and gynecology: experience of a training program in Washington state. The impetus for the development of the Gynecorps Training Program was the identification of medically underserved populations of women in Washington State and their need for preventive health care, the maldistribution of physicians, and the success of a pilot program for training midlevel personnel conducted in 1972 by the Department of Obstetrics and Gynecology, University of Washington School of Medicine. The program trains community-based and -sponsored Registered Nurses and Physician's Assistants as women's health-care specialists, with the goal of delivering preventive care in obstetrics and gynecology to populations of high-risk, low-income, and/or underserved women. A summary of the training program, its curriculum, and the integration of its graduates into community health teams is presented and discussed."}
{"id": "PMID:29488", "title": "Amino acid transport in diaphragms from newborn rats: evidence for insulin resistance.", "content": "Diaphragms from rats under 24-h-old did not show the well-known increased transport of alpha-aminoisobutyrate found in older tissues in respone to insulin in vitro. A small effect was apparent by 3 days, and stimulation increased as donor rats aged (up to 4--5 wk). One-day diaphragms also had greater uptake than older tissues, due to both decreased Km and elevated Vmax. The change in insulin sensitivity did not result from alteration in the transport system used by alpha-aminoisobutyrate because uptake showed characteristics of the A system at both 1 day and older. Results suggest instead that the 1-day tissues had been made insulin-resistant by high insulin levels in donor animals. Plasma insulin levels of 1-day-old rats were 5 times those of 5-day animals. Elevating the plasma insulin levels of 5-day or 25- to 35-day rats led to a decreased effectiveness of insulin in vitro in stimulating alpha-aminoisobutyrate transport into their diaphragms. In the older animals, the stimulation was inversely proportional to the plasma insulin level 2 h after insulin injection.", "contents": "Amino acid transport in diaphragms from newborn rats: evidence for insulin resistance. Diaphragms from rats under 24-h-old did not show the well-known increased transport of alpha-aminoisobutyrate found in older tissues in respone to insulin in vitro. A small effect was apparent by 3 days, and stimulation increased as donor rats aged (up to 4--5 wk). One-day diaphragms also had greater uptake than older tissues, due to both decreased Km and elevated Vmax. The change in insulin sensitivity did not result from alteration in the transport system used by alpha-aminoisobutyrate because uptake showed characteristics of the A system at both 1 day and older. Results suggest instead that the 1-day tissues had been made insulin-resistant by high insulin levels in donor animals. Plasma insulin levels of 1-day-old rats were 5 times those of 5-day animals. Elevating the plasma insulin levels of 5-day or 25- to 35-day rats led to a decreased effectiveness of insulin in vitro in stimulating alpha-aminoisobutyrate transport into their diaphragms. In the older animals, the stimulation was inversely proportional to the plasma insulin level 2 h after insulin injection."}
{"id": "PMID:29490", "title": "Characterization of distal hydrogen ion secretion in acute respiratory alkalosis.", "content": "The effect of acute respiratory alkalosis (ARA) on distal nephron H+ secretion was evaluated by measuring urine-to-blood (U-B) Pco2 in dogs with highly alkaline urine (urine pH greater than 7.8). ARA led to a significant decrease in U-B Pco2 and in urine HCO3 concentration; urine pH, however, increased significantly, indicating that the decrease in urine Pco2 was of greater magnitude than the decrease in urine HCO3 concentration. For any given urine HCO3 concentration urine Pco2 was lower (i.e., urine pH was higher) in ARA than in controls. Administration of tris(hydroxymethyl)aminomethane (Tris) during ARA resulted in a significant increase in U-B Pco2 to control values. In animals with moderately alkaline urine (urine pH 6.4--7.4) and high urine PO4 concentration, ARA resulted in a significant decrease in UB-Pco2 and urine PO4 concentrations. Neutral PO4 infusion in these dogs resulted in an increase in urine PO4 concentration and U-B Pco2 to control levels. These data demonstrate that ARA results in a significant decrease in U-B Pco2 that is not solely attributable to changes in urine HCO3 concentration. The observation that Tris and PO4 infusion during ARA raises U-B Pco2 to control levels suggests that the ability to secrete H+ is intact.", "contents": "Characterization of distal hydrogen ion secretion in acute respiratory alkalosis. The effect of acute respiratory alkalosis (ARA) on distal nephron H+ secretion was evaluated by measuring urine-to-blood (U-B) Pco2 in dogs with highly alkaline urine (urine pH greater than 7.8). ARA led to a significant decrease in U-B Pco2 and in urine HCO3 concentration; urine pH, however, increased significantly, indicating that the decrease in urine Pco2 was of greater magnitude than the decrease in urine HCO3 concentration. For any given urine HCO3 concentration urine Pco2 was lower (i.e., urine pH was higher) in ARA than in controls. Administration of tris(hydroxymethyl)aminomethane (Tris) during ARA resulted in a significant increase in U-B Pco2 to control values. In animals with moderately alkaline urine (urine pH 6.4--7.4) and high urine PO4 concentration, ARA resulted in a significant decrease in UB-Pco2 and urine PO4 concentrations. Neutral PO4 infusion in these dogs resulted in an increase in urine PO4 concentration and U-B Pco2 to control levels. These data demonstrate that ARA results in a significant decrease in U-B Pco2 that is not solely attributable to changes in urine HCO3 concentration. The observation that Tris and PO4 infusion during ARA raises U-B Pco2 to control levels suggests that the ability to secrete H+ is intact."}
{"id": "PMID:29491", "title": "Differences in inducibility by glucocorticoids of rat liver TO and TAT.", "content": "The modulation of tryptophan-oxygenase (TO) and tyrosine amino-transferase (TAT) in the rat liver after a single dose of hydrocortisone has been studied under various physiological conditions. Differences in the induction behavior of the two enzymes have been observed dependent on sex, age, amount of administered hormone, and presence or absence of the adrenals. Some of the results observed are the following: 1) TO reached its maximum induction level 3 h prior to TAT in normal male rats. This difference disappeared when adrenalectomized male rats or when female animals were tested. 2) The maximal induction values of both enzymes were 50--80% higher in adrenalectomized rats than in normal rats. This effect was independent of sex. 3) Higher doses of hydrocortisone were necessary for optimal induction of TO and TAT in normal than in adrenalectomized rats. 4) The minimum dose of hydrocortisone necessary for enzyme induction was significantly lower for TO than for TAT. 5) Actinomycin D caused a complete inhibition of the induction of TO and TAT when given simultaneously with the glucocorticoid. The inhibition was less complete the longer the interval between hormone and actinomycin D administration. The activity of TAT was suppressed to a larger extent than TO.", "contents": "Differences in inducibility by glucocorticoids of rat liver TO and TAT. The modulation of tryptophan-oxygenase (TO) and tyrosine amino-transferase (TAT) in the rat liver after a single dose of hydrocortisone has been studied under various physiological conditions. Differences in the induction behavior of the two enzymes have been observed dependent on sex, age, amount of administered hormone, and presence or absence of the adrenals. Some of the results observed are the following: 1) TO reached its maximum induction level 3 h prior to TAT in normal male rats. This difference disappeared when adrenalectomized male rats or when female animals were tested. 2) The maximal induction values of both enzymes were 50--80% higher in adrenalectomized rats than in normal rats. This effect was independent of sex. 3) Higher doses of hydrocortisone were necessary for optimal induction of TO and TAT in normal than in adrenalectomized rats. 4) The minimum dose of hydrocortisone necessary for enzyme induction was significantly lower for TO than for TAT. 5) Actinomycin D caused a complete inhibition of the induction of TO and TAT when given simultaneously with the glucocorticoid. The inhibition was less complete the longer the interval between hormone and actinomycin D administration. The activity of TAT was suppressed to a larger extent than TO."}
{"id": "PMID:29492", "title": "Ammonia metabolism.", "content": "The pathways responsible for an the mechanisms underlying the adaptive increase in ammonia production in response to acidosis are considered. It seems unlikely that the cytosolic pathways (glutamine synthetase, glutaminase II, phosphate-independent glutaminase, and gamma-glutamyl transferase) are of primary importance in the adaptive process, but the role of the purine nucleotide cycle has not been resolved. The intramitochondrially located phosphate-dependent glutaminase pathway is generally believed to be of primary importance. Adaptation involved either enhanced glutamine entry into the mitrochondria and/or activation of phosphate-dependent glutaminase, but the relative importance of each has not been resolved definitively. The overall adaptive response is probably modulated by factors regulating alpha-ketoglutarate metabolism to phosphoenolpyruvate, and possibly also by metabolism of TCA cycle intermediates. It seems unlikely that a decrease in systemic pH is the direct effector for the acidosis-induced increase in ammonia formation; however, the resulting decrease in urine pH may play a critical role. Other potential messengers, including potassium, glucocorticoids, mineralocorticoids, cyclic AMP, and calcium probably do not serve a primary function, but the importance of other circulating factor(s) is unclear.", "contents": "Ammonia metabolism. The pathways responsible for an the mechanisms underlying the adaptive increase in ammonia production in response to acidosis are considered. It seems unlikely that the cytosolic pathways (glutamine synthetase, glutaminase II, phosphate-independent glutaminase, and gamma-glutamyl transferase) are of primary importance in the adaptive process, but the role of the purine nucleotide cycle has not been resolved. The intramitochondrially located phosphate-dependent glutaminase pathway is generally believed to be of primary importance. Adaptation involved either enhanced glutamine entry into the mitrochondria and/or activation of phosphate-dependent glutaminase, but the relative importance of each has not been resolved definitively. The overall adaptive response is probably modulated by factors regulating alpha-ketoglutarate metabolism to phosphoenolpyruvate, and possibly also by metabolism of TCA cycle intermediates. It seems unlikely that a decrease in systemic pH is the direct effector for the acidosis-induced increase in ammonia formation; however, the resulting decrease in urine pH may play a critical role. Other potential messengers, including potassium, glucocorticoids, mineralocorticoids, cyclic AMP, and calcium probably do not serve a primary function, but the importance of other circulating factor(s) is unclear."}
{"id": "PMID:29493", "title": "Changes in the plasma anion gap during chronic metabolic acid-base disturbances.", "content": "A basic premise in the utilization of the plasma anion gap in the assessment of acid-base disorders is that this parameter remains constant during hyperchloremic metabolic acidosis and metabolic alkalosis. Experimental data under in vitro conditions, however, cast serious doubt on this premise. The purpose of the present study was to characterize the plasma anion gap, estimated as (Na + K) - Cl + HCO3), in two large groups of dogs with graded degrees of chronic, HCl-induced metabolic acidosis or chronic, diuretic-induced metabolic alkalosis. The data indicate that the plasma anion gap decreases significantly in HCl acidosis and increases significantly in metabolic alkalosis; the predicted mean anion gap in animals with a plasma bicarbonate concentration of 10, 21 (normal), and 40 meq/liter approximated 13, 18, and 26 meq/liter, respectively. The observed variation in the plasma anion gap is interpreted as originating mainly from directional changes in the net negative charge of plasma proteins; these changes result from the titration process secondary to the altered plasma acidity and, in the case of metabolic alkalosis, from the additional effect of an increased plasma protein concentration.", "contents": "Changes in the plasma anion gap during chronic metabolic acid-base disturbances. A basic premise in the utilization of the plasma anion gap in the assessment of acid-base disorders is that this parameter remains constant during hyperchloremic metabolic acidosis and metabolic alkalosis. Experimental data under in vitro conditions, however, cast serious doubt on this premise. The purpose of the present study was to characterize the plasma anion gap, estimated as (Na + K) - Cl + HCO3), in two large groups of dogs with graded degrees of chronic, HCl-induced metabolic acidosis or chronic, diuretic-induced metabolic alkalosis. The data indicate that the plasma anion gap decreases significantly in HCl acidosis and increases significantly in metabolic alkalosis; the predicted mean anion gap in animals with a plasma bicarbonate concentration of 10, 21 (normal), and 40 meq/liter approximated 13, 18, and 26 meq/liter, respectively. The observed variation in the plasma anion gap is interpreted as originating mainly from directional changes in the net negative charge of plasma proteins; these changes result from the titration process secondary to the altered plasma acidity and, in the case of metabolic alkalosis, from the additional effect of an increased plasma protein concentration."}
{"id": "PMID:29495", "title": "Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis.", "content": "Metabolic acidosis is known to be associated with increased blood potassium and phosphorus concentrations but the influence of mineral versus nonmineral acids on these variables remains undefined. Therefore, we infused anesthetized mongrel dogs with 0.45% saline (controls), the mineral acids HCl and NH4Cl, and the nonmineral acids lactic, beta-hydroxybutyric and methyl malonic for 1-3 h. Administration of both mineral acids was associated with significant increases in plasma potassium. In contrast, infusion of the three monmineral acids did not result in increases in plasma potassium; in fact, the levels decreased initially in the majority of the dogs. Phosphorus concentrations were increased by lactic and beta-hydroxybutric acids, were unchanged by NH4Cl and HCl, and were decreased by methyl malonic acid. Although the mechanisms responsible for these changes remain to be elucidated, the findings indicate that short-duration infusion of mineral and nonmineral acids has substantially different effects on plasma concentrations of these predominantly intracellular ions.", "contents": "Relationship between blood pH and potassium and phosphorus during acute metabolic acidosis. Metabolic acidosis is known to be associated with increased blood potassium and phosphorus concentrations but the influence of mineral versus nonmineral acids on these variables remains undefined. Therefore, we infused anesthetized mongrel dogs with 0.45% saline (controls), the mineral acids HCl and NH4Cl, and the nonmineral acids lactic, beta-hydroxybutyric and methyl malonic for 1-3 h. Administration of both mineral acids was associated with significant increases in plasma potassium. In contrast, infusion of the three monmineral acids did not result in increases in plasma potassium; in fact, the levels decreased initially in the majority of the dogs. Phosphorus concentrations were increased by lactic and beta-hydroxybutric acids, were unchanged by NH4Cl and HCl, and were decreased by methyl malonic acid. Although the mechanisms responsible for these changes remain to be elucidated, the findings indicate that short-duration infusion of mineral and nonmineral acids has substantially different effects on plasma concentrations of these predominantly intracellular ions."}
{"id": "PMID:29496", "title": "Marijuana use in schizophrenia: a clear hazard.", "content": "The use of marijuana as the independent variable produced a serious exacerbation of a psychotic process in four schizophrenic patients whose illness was otherwise well controlled with antipsychotic medication. Each patient served as his own control--the sole substance abused was marijuana and antipsychotic medication intake remained constant. Each time marijuana use at moderate levels began, there was exacerbation and deterioration. The author suggests that marijuana use is a special hazard to schizophrenic patients and that physicians should alert such high-risk patients to the possible untoward interaction between their illness and marijuana.", "contents": "Marijuana use in schizophrenia: a clear hazard. The use of marijuana as the independent variable produced a serious exacerbation of a psychotic process in four schizophrenic patients whose illness was otherwise well controlled with antipsychotic medication. Each patient served as his own control--the sole substance abused was marijuana and antipsychotic medication intake remained constant. Each time marijuana use at moderate levels began, there was exacerbation and deterioration. The author suggests that marijuana use is a special hazard to schizophrenic patients and that physicians should alert such high-risk patients to the possible untoward interaction between their illness and marijuana."}
{"id": "PMID:29500", "title": "Current medication use and symptoms of depression in a general population.", "content": "In a community survey, 41.8% of 771 men and 60.2% of 1,059 women reported having used one or more medications in the 48 hours before the interview. The use of medications and the number of medications used increased progressively with age among both men and women. Respondents who used four or more medications included significantly more high scores on a depression checklist than those who used fewer medications. The group of women who used minor tranquilizers and sedatives included significantly more high depression scorers than those who did not. Among both sexes, those scoring in the depressed range who were receiving psychotropic medication tended to be taking minor tranquilizers or sedatives.", "contents": "Current medication use and symptoms of depression in a general population. In a community survey, 41.8% of 771 men and 60.2% of 1,059 women reported having used one or more medications in the 48 hours before the interview. The use of medications and the number of medications used increased progressively with age among both men and women. Respondents who used four or more medications included significantly more high scores on a depression checklist than those who used fewer medications. The group of women who used minor tranquilizers and sedatives included significantly more high depression scorers than those who did not. Among both sexes, those scoring in the depressed range who were receiving psychotropic medication tended to be taking minor tranquilizers or sedatives."}
{"id": "PMID:29501", "title": "Psychotropic drugs, summer heat and humidity, and hyperpyrexia: a danger restated.", "content": "The authors note an apparent unawareness of, as well as a paucity of recent literature pertaining to, hyperpyrexia as a complication of psychotropic drug treatment. They report a case of hyperpyrexia in a patient receiving psychotropic agents during a summer heat wave; massive muscle destruction (rhabdomyolysis) with myoglobinuria and acute renal failure make this case of particular interest. Causative mechanisms, preventive measures, and the benefits of prompt recognition and treatment of this condition are discussed.", "contents": "Psychotropic drugs, summer heat and humidity, and hyperpyrexia: a danger restated. The authors note an apparent unawareness of, as well as a paucity of recent literature pertaining to, hyperpyrexia as a complication of psychotropic drug treatment. They report a case of hyperpyrexia in a patient receiving psychotropic agents during a summer heat wave; massive muscle destruction (rhabdomyolysis) with myoglobinuria and acute renal failure make this case of particular interest. Causative mechanisms, preventive measures, and the benefits of prompt recognition and treatment of this condition are discussed."}
{"id": "PMID:29502", "title": "Simple, effective treatment of agoraphobia.", "content": "For effective treatment of agoraphobia both patient and therapist must understand the mechanisms of sensitization and self-desensitization. Rather than aiming to adapt to difficult situations, to achieve desensitization by suggestions, or to avoid panic, the agoraphobe must learn to pass through panic and to rid oneself of drug dependency. This method of self-desensitization will, as a rule, achieve results quickly and does not necessarily depend upon finding the cause of the original sensitization.", "contents": "Simple, effective treatment of agoraphobia. For effective treatment of agoraphobia both patient and therapist must understand the mechanisms of sensitization and self-desensitization. Rather than aiming to adapt to difficult situations, to achieve desensitization by suggestions, or to avoid panic, the agoraphobe must learn to pass through panic and to rid oneself of drug dependency. This method of self-desensitization will, as a rule, achieve results quickly and does not necessarily depend upon finding the cause of the original sensitization."}
{"id": "PMID:29504", "title": "Changes of glycosaminoglycan synthesis during in vitro ageing of human fibroblasts (WI-38).", "content": "Synthesis rates of glycosaminoglycans by WI-38 cultures (diploid, human fibroblasts exhibiting a limited number of population doublings in vitro) were determined by incorporation of 35S-sulfate of 14C-glucosamine into cellular and extracellular glycosaminoglycans at different passage levels before phase out. A progressive decline in the synthesis of cellular and extracellular glycosaminoglycans occured during the last (about 4) population doublings. 35S-sulfate incorporation into extracellular glycosaminoglycans appeared to be somewhat more reduced than 14-C-glucosamine incorporation during the last passages. Analysis of the distribution pattern of incorporated label into various glycosaminoglycan types (hyaluronic acid, chondroitin sulfate, dermatan sulfate and possibly heparan sulfate) revealed an age-related relatively stonger decline of 14C-glucosamine incorporation into cellular and extracellular hyaluronic acid and of 35S-sulfate into extracellular chondroitin sulfate in comparison with the other glycosaminoglycan types. Addition of exogenous glycosaminoglycans (chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, hyaluronic acid, heparan sulfate, heparin) at 100 microgram/ml to the culture media during the last 7 to 10 population doublings before phase out did not increase the total number of population-doublings. Heparin exhibited a significant growth inhibitory effect at 100 or 500 microgram/ml. The changes in glycosaminoglycan metabolism are interpreted as an expression of cellular ageing, and such an in vitro system offers a model for analyzing the factors involved in or causing the induction respectively prevention of this functional change.", "contents": "Changes of glycosaminoglycan synthesis during in vitro ageing of human fibroblasts (WI-38). Synthesis rates of glycosaminoglycans by WI-38 cultures (diploid, human fibroblasts exhibiting a limited number of population doublings in vitro) were determined by incorporation of 35S-sulfate of 14C-glucosamine into cellular and extracellular glycosaminoglycans at different passage levels before phase out. A progressive decline in the synthesis of cellular and extracellular glycosaminoglycans occured during the last (about 4) population doublings. 35S-sulfate incorporation into extracellular glycosaminoglycans appeared to be somewhat more reduced than 14-C-glucosamine incorporation during the last passages. Analysis of the distribution pattern of incorporated label into various glycosaminoglycan types (hyaluronic acid, chondroitin sulfate, dermatan sulfate and possibly heparan sulfate) revealed an age-related relatively stonger decline of 14C-glucosamine incorporation into cellular and extracellular hyaluronic acid and of 35S-sulfate into extracellular chondroitin sulfate in comparison with the other glycosaminoglycan types. Addition of exogenous glycosaminoglycans (chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, hyaluronic acid, heparan sulfate, heparin) at 100 microgram/ml to the culture media during the last 7 to 10 population doublings before phase out did not increase the total number of population-doublings. Heparin exhibited a significant growth inhibitory effect at 100 or 500 microgram/ml. The changes in glycosaminoglycan metabolism are interpreted as an expression of cellular ageing, and such an in vitro system offers a model for analyzing the factors involved in or causing the induction respectively prevention of this functional change."}
{"id": "PMID:29505", "title": "Experimental evidence for a unifying concept of the molecular mechanisms of the cellular aging and the cellular neoplastic transformation.", "content": "Experimental data supporting a Unifying Concept of the molecular mechanisms of cellular aging and cellular neoplastic transformation of dividing cells in mass culture and clonal culture systems will be described. The Unifying Concept combines the hitherto antithetically presented Differentiation Theory, the Mutation Theory, the Error Catastrophy Theory and the Degradation Deficiency Theory with a newly worked out Virus Theory of the cellular aging and the cellular neoplastic transformation. Quantitative in vitro studies of embryonic fibroblast cell systems of two closely related inbred rat strains L.BN and Lewis were undertaken. The data obtained from the experimental analysis of the molecular mechanisms of the cellular aging and the cellular neoplastic transformation demonstrate, that the cellular aging of dividing cells is a Three-Stage-Differentiation Sequence under the control of three different genetic programs. The genetic constitution of the senescent cell regulates the expression of virogenes and oncogenes of the endogenous RNA tumor viruses of the C-type, resulting either in the cellular degeneration of the senescent cell under the control of the virogenes or in the cellular neoplastic transformation regulated by the oncogenes.", "contents": "Experimental evidence for a unifying concept of the molecular mechanisms of the cellular aging and the cellular neoplastic transformation. Experimental data supporting a Unifying Concept of the molecular mechanisms of cellular aging and cellular neoplastic transformation of dividing cells in mass culture and clonal culture systems will be described. The Unifying Concept combines the hitherto antithetically presented Differentiation Theory, the Mutation Theory, the Error Catastrophy Theory and the Degradation Deficiency Theory with a newly worked out Virus Theory of the cellular aging and the cellular neoplastic transformation. Quantitative in vitro studies of embryonic fibroblast cell systems of two closely related inbred rat strains L.BN and Lewis were undertaken. The data obtained from the experimental analysis of the molecular mechanisms of the cellular aging and the cellular neoplastic transformation demonstrate, that the cellular aging of dividing cells is a Three-Stage-Differentiation Sequence under the control of three different genetic programs. The genetic constitution of the senescent cell regulates the expression of virogenes and oncogenes of the endogenous RNA tumor viruses of the C-type, resulting either in the cellular degeneration of the senescent cell under the control of the virogenes or in the cellular neoplastic transformation regulated by the oncogenes."}
{"id": "PMID:29506", "title": "Correlation between DNA repair of embryonic fibroblasts and different life span of 3 inbred mouse strains.", "content": "Primary mouse fibroblast cultures were established from 10 day old embryos of 3 inbred strains with a genetically determined different life expectancy. The capacity for unscheduled DNA synthesis following u.v. irradiation was studied in these cells at various passage levels. The mouse fibroblasts show considerable repair synthesis corresponding to the duration of exposure time. The capacity for induction of unscheduled DNA synthesis was different in the cells of each strain and correlated to the natural life span of the animal; in each case, however, the ability to perform repair synthesis was subjected to an age-associated decline.", "contents": "Correlation between DNA repair of embryonic fibroblasts and different life span of 3 inbred mouse strains. Primary mouse fibroblast cultures were established from 10 day old embryos of 3 inbred strains with a genetically determined different life expectancy. The capacity for unscheduled DNA synthesis following u.v. irradiation was studied in these cells at various passage levels. The mouse fibroblasts show considerable repair synthesis corresponding to the duration of exposure time. The capacity for induction of unscheduled DNA synthesis was different in the cells of each strain and correlated to the natural life span of the animal; in each case, however, the ability to perform repair synthesis was subjected to an age-associated decline."}
{"id": "PMID:29507", "title": "[Stimulation of enzymes of red blood cells by pyridoxal-5-phosphate in dependence on age (author's transl)].", "content": "In 30 students and 43 patients over 60 years the stimulation of enzymes in erythrocytes by pyridoxal-5-phosphate was tested. GOT in blood and erythrocytes was in the old patients diminished and showed higher values after stimulation.", "contents": "[Stimulation of enzymes of red blood cells by pyridoxal-5-phosphate in dependence on age (author's transl)]. In 30 students and 43 patients over 60 years the stimulation of enzymes in erythrocytes by pyridoxal-5-phosphate was tested. GOT in blood and erythrocytes was in the old patients diminished and showed higher values after stimulation."}
{"id": "PMID:29508", "title": "[Age-dependent DNA-content of brain, testis and ovar in men and rats (author's transl)].", "content": "The DNA-content of brain, testis and ovar of Wistar rats (inbred strain) was quantitatively analysed. We observed no significant differences between the several parts of the cerebrum, but between the cerebrum and the cerebellum. Furthermore we demonstrated alterations (with increase and decrease) of the DNA content of all brain parts as well as of testis and ovar during the course of life of this Wistar rat strain. These results and further investigations of the water content as well as of the absolute and of the relative weight of brains of these rats (in comparison to humans) extend the data and our knowledge about these subjects. It is possible to differentiate growth phases (by means of the DNA assays, which correlate with the morphologically well defined growth phases. Finally these results are fundamentals and presuppositions for investigations of the production metabolism of these organs because the DNA content is a better parameter (reference or relation figure, resp.) than the dry or wet weights and the protein or the nitrogen contents.", "contents": "[Age-dependent DNA-content of brain, testis and ovar in men and rats (author's transl)]. The DNA-content of brain, testis and ovar of Wistar rats (inbred strain) was quantitatively analysed. We observed no significant differences between the several parts of the cerebrum, but between the cerebrum and the cerebellum. Furthermore we demonstrated alterations (with increase and decrease) of the DNA content of all brain parts as well as of testis and ovar during the course of life of this Wistar rat strain. These results and further investigations of the water content as well as of the absolute and of the relative weight of brains of these rats (in comparison to humans) extend the data and our knowledge about these subjects. It is possible to differentiate growth phases (by means of the DNA assays, which correlate with the morphologically well defined growth phases. Finally these results are fundamentals and presuppositions for investigations of the production metabolism of these organs because the DNA content is a better parameter (reference or relation figure, resp.) than the dry or wet weights and the protein or the nitrogen contents."}
{"id": "PMID:29509", "title": "[Age-dependent enzymatic changes in human cerebral cortex (author's transl)].", "content": "Little information about the possible neurochemical-enzymatic changes occuring during aging of human brain is available. We, therefore, investigated the activity of various enzymes of human brains obtained at autopsy and covering a range from 19 to 91 years. Protein kinase, which mediates the information carried by the second messenger cAMP, does not show age-related changes of basal activity. Cyclic AMP-dependent activation of protein kinase remains nearly constant up to 60 years of life, but undergoes a distinct and progressive decline between 60 and 90 years. In corpus striatum no age-related changes of cyclic AMP-dependent protein kinase activity were observed. The activity of carbonic anhydrase demonstrates in both human cortex and corpus striatum an age-dependent decrease which also begins after the 6th decade of life. These neurochemical changes are similar to morphological and physiological changes occuring in the aging brain. They begin after the 60th year of life.", "contents": "[Age-dependent enzymatic changes in human cerebral cortex (author's transl)]. Little information about the possible neurochemical-enzymatic changes occuring during aging of human brain is available. We, therefore, investigated the activity of various enzymes of human brains obtained at autopsy and covering a range from 19 to 91 years. Protein kinase, which mediates the information carried by the second messenger cAMP, does not show age-related changes of basal activity. Cyclic AMP-dependent activation of protein kinase remains nearly constant up to 60 years of life, but undergoes a distinct and progressive decline between 60 and 90 years. In corpus striatum no age-related changes of cyclic AMP-dependent protein kinase activity were observed. The activity of carbonic anhydrase demonstrates in both human cortex and corpus striatum an age-dependent decrease which also begins after the 6th decade of life. These neurochemical changes are similar to morphological and physiological changes occuring in the aging brain. They begin after the 60th year of life."}
{"id": "PMID:29510", "title": "[Adenyl cyclase activity and the stimulation of adenosine 3',5'-cyclic monophosphate in blood vessel walls during ageing and under stress (author's transl)].", "content": "It is well-known that the cAMP-adenylate cyclase system is important in mediating the effects of numerous hormones. We investigated the age-dependent behaviour of this system in aortas and femoral arteries of male Wistar rats (at the age of 10 days, 1, 4, 8, 12, and 22 months). It was found that: The basic adenylate cyclase activity had considerably been decreased beyond the first month of life, thereafter it was almost constant. The response of adenylate cyclase to guanylyl-imidodi-phosphate and NaF had essentially been elevated since the 4th month of age. The possibility of stimulating the cAMP generation due to epinephrine and histamine had substantially been increased since the 12th month of age. Besides the ability of adrenaline and histamine to stimulate the formation of cyclic AMP was investigated in broken cell preparation and intact cells of smooth muscle of the aorta and femoral artery of rats which had been subjected to daily intermittend immobilization of 1, 3, and 17 weeks. It was found that this type of stress led to an instability of the blood pressure which was associated with an increase in the sensitivity of adenylate cyclase in the broken cell preparations from the arteries to adrenaline and histamine and with a heightened cyclic AMP response to the two hormones in the intact arterial smooth muscle cells. The sensitivity of cardiac adenylate cyclase for adrenaline remained unchanged.", "contents": "[Adenyl cyclase activity and the stimulation of adenosine 3',5'-cyclic monophosphate in blood vessel walls during ageing and under stress (author's transl)]. It is well-known that the cAMP-adenylate cyclase system is important in mediating the effects of numerous hormones. We investigated the age-dependent behaviour of this system in aortas and femoral arteries of male Wistar rats (at the age of 10 days, 1, 4, 8, 12, and 22 months). It was found that: The basic adenylate cyclase activity had considerably been decreased beyond the first month of life, thereafter it was almost constant. The response of adenylate cyclase to guanylyl-imidodi-phosphate and NaF had essentially been elevated since the 4th month of age. The possibility of stimulating the cAMP generation due to epinephrine and histamine had substantially been increased since the 12th month of age. Besides the ability of adrenaline and histamine to stimulate the formation of cyclic AMP was investigated in broken cell preparation and intact cells of smooth muscle of the aorta and femoral artery of rats which had been subjected to daily intermittend immobilization of 1, 3, and 17 weeks. It was found that this type of stress led to an instability of the blood pressure which was associated with an increase in the sensitivity of adenylate cyclase in the broken cell preparations from the arteries to adrenaline and histamine and with a heightened cyclic AMP response to the two hormones in the intact arterial smooth muscle cells. The sensitivity of cardiac adenylate cyclase for adrenaline remained unchanged."}
{"id": "PMID:29511", "title": "[Histamine H2-receptor blockade and thrombosis prophylaxis with heparin in tetanus. A case report (author's transl)].", "content": "The use of \"low-dose\" heparin for the purpose of the prophylaxis of thrombosis is not yet general in the treatment of tetanus because this therapy may increase the risk of bleeding gastrointestinal stress-ulcers. The combination of heparin with histamine H2-receptor blockers, however, may be of therapeutic benefit and may reduce this complication as well as thrombosis. A case of tetanus and its therapy is reported.", "contents": "[Histamine H2-receptor blockade and thrombosis prophylaxis with heparin in tetanus. A case report (author's transl)]. The use of \"low-dose\" heparin for the purpose of the prophylaxis of thrombosis is not yet general in the treatment of tetanus because this therapy may increase the risk of bleeding gastrointestinal stress-ulcers. The combination of heparin with histamine H2-receptor blockers, however, may be of therapeutic benefit and may reduce this complication as well as thrombosis. A case of tetanus and its therapy is reported."}
{"id": "PMID:29524", "title": "[Neurostimulation--endorphins. Personal opinion in the guise of an introduction].", "content": "Up until 1974 & 1975, Anesthesiologie observed with a certain reserve progress, which was nevertheless spectacular, in the physiological aspects of pain. The fundamental theory of the inhibition of small algophoric fibres by large fibres (NOOR-DENBOS, 1959), the striking theory of spinal control (WALL and MELZACK, 1965) and even the detection of morphine receptors at the same time paradoxically were associated with little enthusiasm here with only a minimum of mention in the journals. Why this lack of enthusiasm? Undoubtedly because new theories remain speculative when viewed from our own standpoint. Since we have been in existence, our methods of general anesthesia have been based upon solid pharmacological concepts but generally paid little attention to physiology which was of relatively little use and even failed to shed any light upon the pharmacology already mentioned. Our attitude was diametrically opposed to that of neurosurgery which by contrast remained within the technical furrow of physiology. The arrival of encephalins forces us to leave behind such attitudes for three reasons: 1--they clearly throw light into the darkness of a whole area of pharmacology; 2--they open up a pharmacological persepective; 3--they raise a number of theoretical and practical questions, which range from their phylogenesis to the hope of one day possessing morphine-like substances without side-effects.", "contents": "[Neurostimulation--endorphins. Personal opinion in the guise of an introduction]. Up until 1974 & 1975, Anesthesiologie observed with a certain reserve progress, which was nevertheless spectacular, in the physiological aspects of pain. The fundamental theory of the inhibition of small algophoric fibres by large fibres (NOOR-DENBOS, 1959), the striking theory of spinal control (WALL and MELZACK, 1965) and even the detection of morphine receptors at the same time paradoxically were associated with little enthusiasm here with only a minimum of mention in the journals. Why this lack of enthusiasm? Undoubtedly because new theories remain speculative when viewed from our own standpoint. Since we have been in existence, our methods of general anesthesia have been based upon solid pharmacological concepts but generally paid little attention to physiology which was of relatively little use and even failed to shed any light upon the pharmacology already mentioned. Our attitude was diametrically opposed to that of neurosurgery which by contrast remained within the technical furrow of physiology. The arrival of encephalins forces us to leave behind such attitudes for three reasons: 1--they clearly throw light into the darkness of a whole area of pharmacology; 2--they open up a pharmacological persepective; 3--they raise a number of theoretical and practical questions, which range from their phylogenesis to the hope of one day possessing morphine-like substances without side-effects."}
{"id": "PMID:29525", "title": "[Current data on pain pathways].", "content": "1--The classical notion attributing the conduction of painful messages to only the A delta and C fibres will be discussed. 2--Spinal cord cells of layers I, V and VIII received painful messages and their physiological properties will be compared. 3--The origin within the cell layers of the spinal cord of the various ascending bundles will be examined. 4--The reticular an thalamic zones (posterior ventra nucleus, mid-line and intralaminar nuclei, GMme posterior group in particular) which receive painful messages have also been studied using activation provoked by pinching, pinprick, the injection of painful substances and stimulation of the dental pulp. The possible role of the different structures thereby brought into action and the limitation of these techniques will be discussed. 5--The existence of metameric controls and controls of central origin active at a spinal, reticular and thalamic level. The absence of inhibitory controls may be responsible for the development of abnormal painful sensations which accompany certain deafferentation procedures. The reestablishment of these controls with the aid of stimulation may result and often results in the improvement of these painful syndromes. 6--Section of the dorsal routes in the chronic animal (rat and cat) may represent an experimental model for deafferentation pain seen in man.", "contents": "[Current data on pain pathways]. 1--The classical notion attributing the conduction of painful messages to only the A delta and C fibres will be discussed. 2--Spinal cord cells of layers I, V and VIII received painful messages and their physiological properties will be compared. 3--The origin within the cell layers of the spinal cord of the various ascending bundles will be examined. 4--The reticular an thalamic zones (posterior ventra nucleus, mid-line and intralaminar nuclei, GMme posterior group in particular) which receive painful messages have also been studied using activation provoked by pinching, pinprick, the injection of painful substances and stimulation of the dental pulp. The possible role of the different structures thereby brought into action and the limitation of these techniques will be discussed. 5--The existence of metameric controls and controls of central origin active at a spinal, reticular and thalamic level. The absence of inhibitory controls may be responsible for the development of abnormal painful sensations which accompany certain deafferentation procedures. The reestablishment of these controls with the aid of stimulation may result and often results in the improvement of these painful syndromes. 6--Section of the dorsal routes in the chronic animal (rat and cat) may represent an experimental model for deafferentation pain seen in man."}
{"id": "PMID:29528", "title": "[Pharmacology of morphine and its derivatives (review)].", "content": "Morphine, the principal alkaloid of \"papaver somniferum\" is the reference substance of central analgesics, the parmacodynamic constants of which are: analgesia and the possibility of addiction. Respiratory depression is, for many of them, a grave side-effect. At the present time, no substance in this category is fully satisfactory and all may result in dependence. Equi-analgesic doses of dextromoramide, phenoperidine and Fentanyl are less than those of morphine, whilst those of pethidine and pentazocine are higher. Study of the pharmacokinetics of these various substances indicates no common elements, and it is difficult to consider that the analgesic action is proportional to blood levels. Clinical assessment of the mean duration of action makes it possible to divide morphine derivatives into substances with a very short action (20 to 45 minutes) such as Febtanyl and phenoperidine, and those with a longer action (1 to 4 hours) which includes the majority of the other substances. The analgesic activity of Methoadone lasts for 4 to 6 hours. Morphine antagonists such as Methadone, nalophine, naloxone and naltrexone possess specific problems in terms of their utilization. Pharmacological data concerning theses substances are described.", "contents": "[Pharmacology of morphine and its derivatives (review)]. Morphine, the principal alkaloid of \"papaver somniferum\" is the reference substance of central analgesics, the parmacodynamic constants of which are: analgesia and the possibility of addiction. Respiratory depression is, for many of them, a grave side-effect. At the present time, no substance in this category is fully satisfactory and all may result in dependence. Equi-analgesic doses of dextromoramide, phenoperidine and Fentanyl are less than those of morphine, whilst those of pethidine and pentazocine are higher. Study of the pharmacokinetics of these various substances indicates no common elements, and it is difficult to consider that the analgesic action is proportional to blood levels. Clinical assessment of the mean duration of action makes it possible to divide morphine derivatives into substances with a very short action (20 to 45 minutes) such as Febtanyl and phenoperidine, and those with a longer action (1 to 4 hours) which includes the majority of the other substances. The analgesic activity of Methoadone lasts for 4 to 6 hours. Morphine antagonists such as Methadone, nalophine, naloxone and naltrexone possess specific problems in terms of their utilization. Pharmacological data concerning theses substances are described."}
{"id": "PMID:29530", "title": "[Morphine analgesia: neurobiologic data].", "content": "Recent Neurobiological (Neurophysiological, Histochemical, Neurochemical and behavioural studies) data have indicated that the analgesic effects of morphine may, at least in part, be explained by two modes of action. A--Morphine has a direct depressive action at a spinal level on the activity of neurones of the grey matter of the dorsal horn which run towards the higher centres of the encephalon. These effects are exerted preferentially on activities induced by the activity of fine non-myelinized fibres (C). These mechanisms are discussed taking into account recent data concerning polypeptides (substance P and encephalins). B--Morphine acts at the level of the brain stem (periaqueductal grey matter, raphian nucleus, etc.) reinforcing the activity of descending bulbo-spinal pathways which block the transmission of painful messages within the cord.", "contents": "[Morphine analgesia: neurobiologic data]. Recent Neurobiological (Neurophysiological, Histochemical, Neurochemical and behavioural studies) data have indicated that the analgesic effects of morphine may, at least in part, be explained by two modes of action. A--Morphine has a direct depressive action at a spinal level on the activity of neurones of the grey matter of the dorsal horn which run towards the higher centres of the encephalon. These effects are exerted preferentially on activities induced by the activity of fine non-myelinized fibres (C). These mechanisms are discussed taking into account recent data concerning polypeptides (substance P and encephalins). B--Morphine acts at the level of the brain stem (periaqueductal grey matter, raphian nucleus, etc.) reinforcing the activity of descending bulbo-spinal pathways which block the transmission of painful messages within the cord."}
{"id": "PMID:29533", "title": "[Opiate receptors and endorphins at the central nervous system level].", "content": "Four years ago, sterospecific sites for the bending of opiates were discovered within the brain of animals and the human being. All of the properties of these sites are in conformity with the proposition that they are pharmacological receptors which have long been postulated for these drugs. The binding of morphine or of one of its derivatives to these sites should result in chemical or physical reactions leading to well known pharmacological responses. These reactions following the binding of drugs to the receptors are not yet known, but there is some evidence that cyclical nucleotides play a role. The affinity of a whole series of morphine derivatives, agonists and atagonists, is well correlated with their pharmacological effectiveness. In the presence of sodium salts, antagonists become more strongly bound and agonists less strongly than in the absence of sodium. The evidence is presented. This is explained by an equilibrium between two formations of the receptor: one characteristic of the absence of sodium and one of its presence. Receptors are found in the nervous system of all vertebrates and their distribution has been studied in the human brain. The regions with the highest concentration of receptors are those of the limbic system. A high level exists also in the \"substantia gelatinosa\" of the spinal cord, which is involved in the passage of painful messages. Study of the function of morphine receptors has led to the isolation, in animal brain, of a number of peptides with morphine properties named endorphines. The first two endorphines isolated were pentapeptides named encephalins. The properties of endorphines from the subject of several lecture in this course.", "contents": "[Opiate receptors and endorphins at the central nervous system level]. Four years ago, sterospecific sites for the bending of opiates were discovered within the brain of animals and the human being. All of the properties of these sites are in conformity with the proposition that they are pharmacological receptors which have long been postulated for these drugs. The binding of morphine or of one of its derivatives to these sites should result in chemical or physical reactions leading to well known pharmacological responses. These reactions following the binding of drugs to the receptors are not yet known, but there is some evidence that cyclical nucleotides play a role. The affinity of a whole series of morphine derivatives, agonists and atagonists, is well correlated with their pharmacological effectiveness. In the presence of sodium salts, antagonists become more strongly bound and agonists less strongly than in the absence of sodium. The evidence is presented. This is explained by an equilibrium between two formations of the receptor: one characteristic of the absence of sodium and one of its presence. Receptors are found in the nervous system of all vertebrates and their distribution has been studied in the human brain. The regions with the highest concentration of receptors are those of the limbic system. A high level exists also in the \"substantia gelatinosa\" of the spinal cord, which is involved in the passage of painful messages. Study of the function of morphine receptors has led to the isolation, in animal brain, of a number of peptides with morphine properties named endorphines. The first two endorphines isolated were pentapeptides named encephalins. The properties of endorphines from the subject of several lecture in this course."}
{"id": "PMID:29535", "title": "[Electrophysiological effects of opiates and endogenous peptides on central neurons].", "content": "The influence of micro-iontophoretically administered opiates and opiate peptides on the activity of single neurones in the central nervous system will be discussed. It will be shown that in single neurone studies in several different supraspinal regions opiates and opiate peptides have similar actions on individual neurones and both may excite or depress neuronal activity. The excitatory and inhibitory effects of these substances can be reversed by a necrotic antagonist and therefore may be mediated via an action at specific opiate receptors. Studies on spinal neurons indicate that the excitatory action of morphine and enkephalin may be due to an interaction with a cholinergic receptor or at least cholinoceptive neurones. Evidence will also be presented showing that responses of dorsal horn neurones to nowious peripheral stimuli may be selectively reduced by morphine and enkephalin administered into the substantia gelatinosa region or the spinal cord. The relevance of these observations to the pharmacological action of opiates and the possible physiological function of endogenous opiate peptides will be mentioned.", "contents": "[Electrophysiological effects of opiates and endogenous peptides on central neurons]. The influence of micro-iontophoretically administered opiates and opiate peptides on the activity of single neurones in the central nervous system will be discussed. It will be shown that in single neurone studies in several different supraspinal regions opiates and opiate peptides have similar actions on individual neurones and both may excite or depress neuronal activity. The excitatory and inhibitory effects of these substances can be reversed by a necrotic antagonist and therefore may be mediated via an action at specific opiate receptors. Studies on spinal neurons indicate that the excitatory action of morphine and enkephalin may be due to an interaction with a cholinergic receptor or at least cholinoceptive neurones. Evidence will also be presented showing that responses of dorsal horn neurones to nowious peripheral stimuli may be selectively reduced by morphine and enkephalin administered into the substantia gelatinosa region or the spinal cord. The relevance of these observations to the pharmacological action of opiates and the possible physiological function of endogenous opiate peptides will be mentioned."}
{"id": "PMID:29537", "title": "[Transcutaneous electrotherapy in the treatment of chronic post-zoster pain].", "content": "Transcutaneous electrotherapy has been employed in 112 patients with chronic pains of various origins. The immediate and long term results are not considered, at whole, satisfactory, especially for length and quality of the obtained improvement. Only patients with chronic post-zoosterian neuralgia had good results, or immediate either at long term, especially in intercostal pains. In the contrary in acute cases of this nevralgia, there were not satisfactory improvements.", "contents": "[Transcutaneous electrotherapy in the treatment of chronic post-zoster pain]. Transcutaneous electrotherapy has been employed in 112 patients with chronic pains of various origins. The immediate and long term results are not considered, at whole, satisfactory, especially for length and quality of the obtained improvement. Only patients with chronic post-zoosterian neuralgia had good results, or immediate either at long term, especially in intercostal pains. In the contrary in acute cases of this nevralgia, there were not satisfactory improvements."}
{"id": "PMID:29538", "title": "[Effects of percutaneous heterosegmental electric stimulation (electro-acupuncture) on the nociceptive flexion reflex in man].", "content": "A comparative study of the effects of electro-acupuncture of the HO KU point and of a placebo control point were carried out in man, taking as an objective test of pain the threshold of a pain induced flexion reflex. In the absence of electrical stimulation of the HO KU point, or of the control point, no variation in the painful reflex threshold was seen. This remained stable throughout the experimental session. However, electrical stimulation of the HO KU point resulted in a 115 p. 100 increase in the reflex threshold, whilst that of the control point resulted in an increase of 20 p. 100 in the threshold of the same reflex. These results are discussed on the basis of data in the literature.", "contents": "[Effects of percutaneous heterosegmental electric stimulation (electro-acupuncture) on the nociceptive flexion reflex in man]. A comparative study of the effects of electro-acupuncture of the HO KU point and of a placebo control point were carried out in man, taking as an objective test of pain the threshold of a pain induced flexion reflex. In the absence of electrical stimulation of the HO KU point, or of the control point, no variation in the painful reflex threshold was seen. This remained stable throughout the experimental session. However, electrical stimulation of the HO KU point resulted in a 115 p. 100 increase in the reflex threshold, whilst that of the control point resulted in an increase of 20 p. 100 in the threshold of the same reflex. These results are discussed on the basis of data in the literature."}
{"id": "PMID:29539", "title": "[Modulation of experimental dental pain in man with acupuncture and by transcutaneous electric stimulation].", "content": "We have studied the effects of electrical acupuncture stimulation and transcutaneous electrical stimulation on the ability of human volunteers to perceive pain. Both psychophysical indices and measures of cerebral evoked responses to painful stimuli have been used to demonstrate that these treatments reduce pain perception. A recently completed study showed that the analgesic effects of transcutaneous electrical stimulation can be partly reversed when 0,4 mg of naloxone is injected. This observation suggests that endogenic morphine-like peptides are released in response to low frequency electrical stimulation of the skin.", "contents": "[Modulation of experimental dental pain in man with acupuncture and by transcutaneous electric stimulation]. We have studied the effects of electrical acupuncture stimulation and transcutaneous electrical stimulation on the ability of human volunteers to perceive pain. Both psychophysical indices and measures of cerebral evoked responses to painful stimuli have been used to demonstrate that these treatments reduce pain perception. A recently completed study showed that the analgesic effects of transcutaneous electrical stimulation can be partly reversed when 0,4 mg of naloxone is injected. This observation suggests that endogenic morphine-like peptides are released in response to low frequency electrical stimulation of the skin."}
{"id": "PMID:29540", "title": "[Modes of action of various aspects of analgesia by stimulation].", "content": "A study of 12 patients suffering from chronic lumbar pain led to a comparison of the results of treatment with traditional acupuncture and that with transcutaneous electrical stimulation. The degree and quality of pain, as well as the duration of relief after treatment, were analyzed in an attempt to differentiate between the two forms of analgesia. Statistical analysis of the two methods showed no significant difference. Not only did they appear to have the same therapeutic merit, but it would also seem reasonable to suppose that they have a common mechanism at their origin. Intense stimulation of trigger points followed by relief of pain led us to compare them to acupuncture zones both in terms of topography and characteristics. There was a certain analogy of distribution, associated with a similarity of expression which led us to consider that these two techniques were possibly related to the same neurological process.", "contents": "[Modes of action of various aspects of analgesia by stimulation]. A study of 12 patients suffering from chronic lumbar pain led to a comparison of the results of treatment with traditional acupuncture and that with transcutaneous electrical stimulation. The degree and quality of pain, as well as the duration of relief after treatment, were analyzed in an attempt to differentiate between the two forms of analgesia. Statistical analysis of the two methods showed no significant difference. Not only did they appear to have the same therapeutic merit, but it would also seem reasonable to suppose that they have a common mechanism at their origin. Intense stimulation of trigger points followed by relief of pain led us to compare them to acupuncture zones both in terms of topography and characteristics. There was a certain analogy of distribution, associated with a similarity of expression which led us to consider that these two techniques were possibly related to the same neurological process."}
{"id": "PMID:29542", "title": "[Chronic intracerebral electric stimulation for analgesia in man].", "content": "This report concerns the current status of the results of intraencephalic implantations carried out up to the present time in man with the aim of relieving certain forms of chronic pain. It places little emphasis upon the neuro-physiological basis of these implantations, which have been studied at length during previous reports. After presenting the overall results of operations carried out in the world up until September 1967, a critical study is undertaken: 1--In relation to the targets (Postero-Lateral Ventral Nucleus, posterior arm of the internal capsule, para-ventricular thalamic grey matter). 2--In relation to etiologies, both analytically (syndrome) by syndrome as well as in terms of synthesis (excess of pain perception-deafferentation). 3--In terms of various factors, such as: --technical requirements; --side ffects; --duration of \"post effect\" (residual analgesia after stimulation); --parallel action of drugs. Conclusions are drawn concerning future perspectives of this technique.", "contents": "[Chronic intracerebral electric stimulation for analgesia in man]. This report concerns the current status of the results of intraencephalic implantations carried out up to the present time in man with the aim of relieving certain forms of chronic pain. It places little emphasis upon the neuro-physiological basis of these implantations, which have been studied at length during previous reports. After presenting the overall results of operations carried out in the world up until September 1967, a critical study is undertaken: 1--In relation to the targets (Postero-Lateral Ventral Nucleus, posterior arm of the internal capsule, para-ventricular thalamic grey matter). 2--In relation to etiologies, both analytically (syndrome) by syndrome as well as in terms of synthesis (excess of pain perception-deafferentation). 3--In terms of various factors, such as: --technical requirements; --side ffects; --duration of \"post effect\" (residual analgesia after stimulation); --parallel action of drugs. Conclusions are drawn concerning future perspectives of this technique."}
{"id": "PMID:29550", "title": "Differential responsiveness of central noradrenergic and dopaminergic neuron tyrosine hydroxylase to hypophysectomy, ACTH and glucocorticoid administration.", "content": "Hypophysectomy leads to a small increase in tyrosine hydroxylase activity of all brain areas containing noradrenergic neurons or tuberoinfundibular dopamine neurons, but nigroneostriatal dopamine neurons are not so affected. ACTH or corticosterone treatment inhibited this effect of hypophysectomy in some noradrenergic neurons and in tuberoinfundibular dopamine neurons. These data showing differential responsiveness of tyrosine hydroxylase in different brain areas are compatible with differences in regulation or molecular form of tyrosine hydroxylase in central noradrenergic and dopaminergic neurons. The disparity between increased hypothalamic tyrosine hydroxylase activity and decreased norepinephrine turnover following hypophysectomy may result from a change in the rate-limiting step to the hydroxylation of dopamine.", "contents": "Differential responsiveness of central noradrenergic and dopaminergic neuron tyrosine hydroxylase to hypophysectomy, ACTH and glucocorticoid administration. Hypophysectomy leads to a small increase in tyrosine hydroxylase activity of all brain areas containing noradrenergic neurons or tuberoinfundibular dopamine neurons, but nigroneostriatal dopamine neurons are not so affected. ACTH or corticosterone treatment inhibited this effect of hypophysectomy in some noradrenergic neurons and in tuberoinfundibular dopamine neurons. These data showing differential responsiveness of tyrosine hydroxylase in different brain areas are compatible with differences in regulation or molecular form of tyrosine hydroxylase in central noradrenergic and dopaminergic neurons. The disparity between increased hypothalamic tyrosine hydroxylase activity and decreased norepinephrine turnover following hypophysectomy may result from a change in the rate-limiting step to the hydroxylation of dopamine."}
{"id": "PMID:29546", "title": "[Polyol dehydrogenases in mycobacteria (author's transl)].", "content": "Contrary to the the tubercle bacilli (H37Ra, BCG), Mycobacterium phlei, grown on Sauton medium, formed the NAD+ dependent dehydrogenases that catalyse the oxidation of ribitol, sorbitol and mannitol. These enzymes were separated by chromatography on DEAE-cellulose and Sephadex G-200. In the present work we have principally studied the ribitol dehydrogenase. All the experiments for induction of the ribitol dehydrogenase in H37Ra or BCG were negative; whereas after the adaptation of M. phlei to ribitol, the specific activity of this enzyme increased in the supernatants more than 100 per cent. The ribitol dehydrogenase of M. phlei reduced NAD+ not only in the presence of ribitol but also (though to a lesser extent) in the presence of erythritol and glycerol. Other properties studied concerning this enzyme and the reaction it catalyses were: pH dependence, equilibrium constant, Km and sensitivity towards the inhibitors of the thiol groups.", "contents": "[Polyol dehydrogenases in mycobacteria (author's transl)]. Contrary to the the tubercle bacilli (H37Ra, BCG), Mycobacterium phlei, grown on Sauton medium, formed the NAD+ dependent dehydrogenases that catalyse the oxidation of ribitol, sorbitol and mannitol. These enzymes were separated by chromatography on DEAE-cellulose and Sephadex G-200. In the present work we have principally studied the ribitol dehydrogenase. All the experiments for induction of the ribitol dehydrogenase in H37Ra or BCG were negative; whereas after the adaptation of M. phlei to ribitol, the specific activity of this enzyme increased in the supernatants more than 100 per cent. The ribitol dehydrogenase of M. phlei reduced NAD+ not only in the presence of ribitol but also (though to a lesser extent) in the presence of erythritol and glycerol. Other properties studied concerning this enzyme and the reaction it catalyses were: pH dependence, equilibrium constant, Km and sensitivity towards the inhibitors of the thiol groups."}
{"id": "PMID:29554", "title": "Ocular hypotensive efficacy of topical epinephrine in normotensive and hypertensive rabbits: continuous drug delivery vs eyedrops.", "content": "The ocular hypotensive efficacy of continuously delivered epinephrine is compared to that of pulsed doses provided by eyedrops in both normotensive and hypertensive rabbit eyes. In normotensive eyes, 2 microgram/hr and 4 microgram/hr epinephrine delivered into the tear film continuously for 12 hours reduces intraocular pressure as well as eyedrop pulses of 0.5% epinephrine hydrochloride or 2% epinephrine bitartrate (doses of 500 and 1100 microgram, respectively). Ocular hypertension induced by an intragastric water load in rabbits is significantly inhibited by continuous delivery of epinephrine at the rates of 3 or 6 microgram/hr, or by 2% epinephrine bitartrate (1% free base) eyedrops. Epinephrine delivered continuously at rates of 2-6 microgram/hr for 6 to 12 hours (12-72 microgram total) has hypotensive efficacy equivalent to 15 to 40 times as much epinephrine applied once in eyedrops. Epinephrine bitartrate eyedrops reduce tear film pH well below normal. Continuous delivery of epinephrine bitartrate does not reduce tear film pH below normal levels.", "contents": "Ocular hypotensive efficacy of topical epinephrine in normotensive and hypertensive rabbits: continuous drug delivery vs eyedrops. The ocular hypotensive efficacy of continuously delivered epinephrine is compared to that of pulsed doses provided by eyedrops in both normotensive and hypertensive rabbit eyes. In normotensive eyes, 2 microgram/hr and 4 microgram/hr epinephrine delivered into the tear film continuously for 12 hours reduces intraocular pressure as well as eyedrop pulses of 0.5% epinephrine hydrochloride or 2% epinephrine bitartrate (doses of 500 and 1100 microgram, respectively). Ocular hypertension induced by an intragastric water load in rabbits is significantly inhibited by continuous delivery of epinephrine at the rates of 3 or 6 microgram/hr, or by 2% epinephrine bitartrate (1% free base) eyedrops. Epinephrine delivered continuously at rates of 2-6 microgram/hr for 6 to 12 hours (12-72 microgram total) has hypotensive efficacy equivalent to 15 to 40 times as much epinephrine applied once in eyedrops. Epinephrine bitartrate eyedrops reduce tear film pH well below normal. Continuous delivery of epinephrine bitartrate does not reduce tear film pH below normal levels."}
{"id": "PMID:29555", "title": "Improved methods for detecting enteric viruses in oysters.", "content": "New and improved methods for concentrating enteroviruses, reoviruses, and adenoviruses from oysters have been developed and evaluated. Viruses are efficiently adsorbed to homogenized oyster meat by adjusting the homogenate to pH 5.0 and a conductivity of less than or equal to 2,000 mg of NaCl per liter. After low-speed centrifugation, the virus-free supernatant is discarded and the viruses are eluted from the sedimented oyster solids with pH 7.5 glycine-NaCl having a conductivity of 8,000 mg of NaCl per liter. The oyster solids are removed by low-speed centrifugation and filtration, and the viruses in the filtered supernatant are concentrated to a small volume by either ultrafiltration or acid precipitation at pH 4.5. The concentrate is treated with antibiotics and inoculated into cell cultures for virus isolation and quantitation. When these methods were tested with oysters experimentally contaminated with polioviruses, reoviruses, and adenoviruses, recovery efficiencies averaged about 46%. With the exception of virus assay and quantitation, these methods are simple and inexpensive enough to be done in typical shellfish microbiology laboratories.", "contents": "Improved methods for detecting enteric viruses in oysters. New and improved methods for concentrating enteroviruses, reoviruses, and adenoviruses from oysters have been developed and evaluated. Viruses are efficiently adsorbed to homogenized oyster meat by adjusting the homogenate to pH 5.0 and a conductivity of less than or equal to 2,000 mg of NaCl per liter. After low-speed centrifugation, the virus-free supernatant is discarded and the viruses are eluted from the sedimented oyster solids with pH 7.5 glycine-NaCl having a conductivity of 8,000 mg of NaCl per liter. The oyster solids are removed by low-speed centrifugation and filtration, and the viruses in the filtered supernatant are concentrated to a small volume by either ultrafiltration or acid precipitation at pH 4.5. The concentrate is treated with antibiotics and inoculated into cell cultures for virus isolation and quantitation. When these methods were tested with oysters experimentally contaminated with polioviruses, reoviruses, and adenoviruses, recovery efficiencies averaged about 46%. With the exception of virus assay and quantitation, these methods are simple and inexpensive enough to be done in typical shellfish microbiology laboratories."}
{"id": "PMID:29556", "title": "Comparative effects of ammonia and related compounds on poliovirus.", "content": "The abilities of ammonia and related compounds to inactivate poliovirus were compared. Compounds virucidal at pH 9.5 had the following order of activities: ethylamine greater than propylamine, dimethylamine, methylamine greater than ammonia greater than 2-methoxyethylamine.", "contents": "Comparative effects of ammonia and related compounds on poliovirus. The abilities of ammonia and related compounds to inactivate poliovirus were compared. Compounds virucidal at pH 9.5 had the following order of activities: ethylamine greater than propylamine, dimethylamine, methylamine greater than ammonia greater than 2-methoxyethylamine."}
{"id": "PMID:29557", "title": "Characteristics of bacteriophages for Micromonospora purpurea.", "content": "Chemical and physical stabilities of bacteriophages \u00f8UW 21 and \u00f8UW 51 infecting Micromonospora purpurea ATCC 15835 were examined. Both phages were stable over the pH range of 5 to 8 and to heating at temperatures up to 50 degrees C and especially stable in buffer containing magnesium ion. Exposure to 1 M Ca(NO3)2 inactivated both phages, and phage \u00f8UW 51 was also susceptible to 1 M CaCl2, 0.1 M tris(hydroxymethyl)aminomethane, and 0.3% H2O2. Phage plating efficiency was highest on the cultures at logarithmic phase and sometimes much influenced by host growth. Phage \u00f8UW 51 has a latent period of 2 h at 34 degrees C and a burst size between 35 and 40. The latent period for phage \u00f8UW 21 is about 12 h, and the burst size is smaller than 30.", "contents": "Characteristics of bacteriophages for Micromonospora purpurea. Chemical and physical stabilities of bacteriophages \u00f8UW 21 and \u00f8UW 51 infecting Micromonospora purpurea ATCC 15835 were examined. Both phages were stable over the pH range of 5 to 8 and to heating at temperatures up to 50 degrees C and especially stable in buffer containing magnesium ion. Exposure to 1 M Ca(NO3)2 inactivated both phages, and phage \u00f8UW 51 was also susceptible to 1 M CaCl2, 0.1 M tris(hydroxymethyl)aminomethane, and 0.3% H2O2. Phage plating efficiency was highest on the cultures at logarithmic phase and sometimes much influenced by host growth. Phage \u00f8UW 51 has a latent period of 2 h at 34 degrees C and a burst size between 35 and 40. The latent period for phage \u00f8UW 21 is about 12 h, and the burst size is smaller than 30."}
{"id": "PMID:29558", "title": "Inactivation of enteroviruses by ascorbic acid and sodium bisulfite.", "content": "Poliovirus type 1, coxsackievirus type A9, and echovirus type 7 were inactivated by sodium bisulfite and ascorbic acid. Inactivation rates depended upon concentration, temperature, and pH. RNA infectivity was lost during inactivation; the capsid was also altered by these inactivating agents, as determined by enzyme sensitivity assays and by tests of adsorption to cells. Structural modifications of the virus particles were not identical, suggesting that the mechanism of inactivation by ascorbic acid differs from that of sodium bisulfite.", "contents": "Inactivation of enteroviruses by ascorbic acid and sodium bisulfite. Poliovirus type 1, coxsackievirus type A9, and echovirus type 7 were inactivated by sodium bisulfite and ascorbic acid. Inactivation rates depended upon concentration, temperature, and pH. RNA infectivity was lost during inactivation; the capsid was also altered by these inactivating agents, as determined by enzyme sensitivity assays and by tests of adsorption to cells. Structural modifications of the virus particles were not identical, suggesting that the mechanism of inactivation by ascorbic acid differs from that of sodium bisulfite."}
{"id": "PMID:29559", "title": "Development of quantitative methods for the detection of enteroviruses in sewage sludges during activation and following land disposal.", "content": "The development and evaluation of methods for the quantitative recovery of enteroviruses from sewage sludge are reported. Activated sewage sludge solids were collected by centrifugation, and elution of the solid-associated virus was accomplished by mechanical agitation in glycine buffer at pH 11.0. Eluted viruses were concentrated either onto an aluminum hydroxide floc or by association with a floc which formed de novo upon adjustment of the glycine eluate to pH 3.5. Viruses which remained in the liquid phase after lowering the pH of glycine eluate were concentrated by adsorption to and elution from membrane filters. The method of choice included high pH glycine elution and subsequent low pH concentration; it yielded an efficiency of recovery from activated sludge of 80% for poliovirus type 1, 68% for echovirus type 7, and 75% for coxsackievirus B3. This method was used to study the survival of naturally occurring virus in sludge at a sewage treatment plant and after subsequent land disposal of the solids after aerobic digestion. Reduction of enterovirus titers per gram (dry weight) of solids were modest during sludge activation but increased to a rate of 2 log 10/week after land disposal.", "contents": "Development of quantitative methods for the detection of enteroviruses in sewage sludges during activation and following land disposal. The development and evaluation of methods for the quantitative recovery of enteroviruses from sewage sludge are reported. Activated sewage sludge solids were collected by centrifugation, and elution of the solid-associated virus was accomplished by mechanical agitation in glycine buffer at pH 11.0. Eluted viruses were concentrated either onto an aluminum hydroxide floc or by association with a floc which formed de novo upon adjustment of the glycine eluate to pH 3.5. Viruses which remained in the liquid phase after lowering the pH of glycine eluate were concentrated by adsorption to and elution from membrane filters. The method of choice included high pH glycine elution and subsequent low pH concentration; it yielded an efficiency of recovery from activated sludge of 80% for poliovirus type 1, 68% for echovirus type 7, and 75% for coxsackievirus B3. This method was used to study the survival of naturally occurring virus in sludge at a sewage treatment plant and after subsequent land disposal of the solids after aerobic digestion. Reduction of enterovirus titers per gram (dry weight) of solids were modest during sludge activation but increased to a rate of 2 log 10/week after land disposal."}
{"id": "PMID:29560", "title": "Hydrogen peroxide and superoxide radical formation in anaerobic broth media exposed to atmospheric oxygen.", "content": "Fourteen different broth media were autoclaved under anaerobic conditions and then exposed to atmospheric oxygen. The hydrogen peroxide and superoxide radical formation as well as the bactericidal effect of the media were studied. The rate of killing of Peptostreptococcus anaerobius VPI 4330-1 was high in media that rapidly autoxidized and accumulated hydrogen peroxide. In actinomyces broth (BBL), 50% of the cells were killed within 2 min, and in Brewer thioglycolate medium (Difco), 50% were killed within 11 min, whereas more than 50% of the cells survived for more than 2 h in Clausen medium (Oxoid), fluid thioglycolate medium (BBL), and thioglycolate medium without dextrose or indicator (Difco). Only media that contained phosphate and glucose had a tendency to accumulate hydrogen peroxide. A solution of phosphate and glucose autoxidized when it had been heated to 120 degrees C for at least 5 min and when the pH of the solution was higher than 6.5. Transitional metal ions catalyzed the autoxidation, but they were not necessary for the reaction to occur. Of the other substances heated in phosphate buffer, only alpha-hydroxycarbonyl compounds autoxidized with accumulation of hydrogen peroxide. Superoxide dismutase decreased the autoxidation rate of most of the broth media. This indicated that superoxide radicals were generated in these media.", "contents": "Hydrogen peroxide and superoxide radical formation in anaerobic broth media exposed to atmospheric oxygen. Fourteen different broth media were autoclaved under anaerobic conditions and then exposed to atmospheric oxygen. The hydrogen peroxide and superoxide radical formation as well as the bactericidal effect of the media were studied. The rate of killing of Peptostreptococcus anaerobius VPI 4330-1 was high in media that rapidly autoxidized and accumulated hydrogen peroxide. In actinomyces broth (BBL), 50% of the cells were killed within 2 min, and in Brewer thioglycolate medium (Difco), 50% were killed within 11 min, whereas more than 50% of the cells survived for more than 2 h in Clausen medium (Oxoid), fluid thioglycolate medium (BBL), and thioglycolate medium without dextrose or indicator (Difco). Only media that contained phosphate and glucose had a tendency to accumulate hydrogen peroxide. A solution of phosphate and glucose autoxidized when it had been heated to 120 degrees C for at least 5 min and when the pH of the solution was higher than 6.5. Transitional metal ions catalyzed the autoxidation, but they were not necessary for the reaction to occur. Of the other substances heated in phosphate buffer, only alpha-hydroxycarbonyl compounds autoxidized with accumulation of hydrogen peroxide. Superoxide dismutase decreased the autoxidation rate of most of the broth media. This indicated that superoxide radicals were generated in these media."}
{"id": "PMID:29561", "title": "Presence and partial characterization of internal acid protease of Aspergillus oryzae.", "content": "The presence and partial characterization of the internal acid protease (EC 2.4.23.6) of Aspergillus oryzae has been investigated. Although the majority of the acid protease is external and present in the culture filtrate, a significant amount of the active enzyme is firmly bound to the cells; it is not released by repeated extraction of cells with 0.9% sodium chloride but is liberated into the soluble fraction during disruption of cells. The internal acid protease, as well as the external one, was separated into two major molecular forms (F1 and F2) with molecular weights of 60,000 and 42,000, respectively, by chromatography on Sephadex G-100 and on CM-Sephadex C-50. The partially purified internal enzymes had the same catalytic and immunological properties, as did the external enzyme.", "contents": "Presence and partial characterization of internal acid protease of Aspergillus oryzae. The presence and partial characterization of the internal acid protease (EC 2.4.23.6) of Aspergillus oryzae has been investigated. Although the majority of the acid protease is external and present in the culture filtrate, a significant amount of the active enzyme is firmly bound to the cells; it is not released by repeated extraction of cells with 0.9% sodium chloride but is liberated into the soluble fraction during disruption of cells. The internal acid protease, as well as the external one, was separated into two major molecular forms (F1 and F2) with molecular weights of 60,000 and 42,000, respectively, by chromatography on Sephadex G-100 and on CM-Sephadex C-50. The partially purified internal enzymes had the same catalytic and immunological properties, as did the external enzyme."}
{"id": "PMID:29562", "title": "Prevalence of fungi during Skylab missions.", "content": "Samples for mycological analysis were collected from surfaces in the Skylab spacecraft before launch and during flight for each manned mission. Fungal contamination levels were low during the first two flights; however, the species recovered were different for each mission. On the third mission, widespread contamination of the Skylab spacecraft with Aspergillus and Pencillium spp. was detected. This contamination was traced to several contaminated space suit undergarments.", "contents": "Prevalence of fungi during Skylab missions. Samples for mycological analysis were collected from surfaces in the Skylab spacecraft before launch and during flight for each manned mission. Fungal contamination levels were low during the first two flights; however, the species recovered were different for each mission. On the third mission, widespread contamination of the Skylab spacecraft with Aspergillus and Pencillium spp. was detected. This contamination was traced to several contaminated space suit undergarments."}
{"id": "PMID:29563", "title": "Phthalate and 4-hydroxyphthalate metabolism in Pseudomonas testosteroni: purification and properties of 4,5-dihydroxyphthalate decarboxylase.", "content": "Phthalate is degraded through 4,5-dihydroxyphthalate and protocatechuate in Pseudomonas testosteroni NH1000. The ezyme 4,5-dihydroxyphthalate decarboxylase, catalyzing the conversion of 4,5-dihydroxyphthalate to protocatechuate and carbon dioxide, was purified approximately 130-fold from phthalate-induced cells of a protocatechuate 4,5-dioxygenase-deficient mutant of P. testosteroni. The most purified preparation showed a single protein band on sodium dodecyl sulfate-acrylamide disc gel electrophoresis with a molecular weight of 38,000. The apparent molecular weight of the native enzyme determined by Sephadex G-200 column chromatography was 150,000. Among the substrate analogs tested, only 4-hydroxyphthalate served as a substrate, which was decarboxylated to form m-hydroxybenzoate. The apparent Km values for 4,5-dihydroxyphthalate and 4-hydroxyphthalate were estimated to be 10.5 micrometer and 1.25 mM, respectively, and the Vmax for the former was 10 times larger than that for the latter. Whereas the wild-type strain could utilize 4-hydroxyphthalate as a sole source of carbon, none of the following could grow with the compound: 4,5-dihydroxyphthalate decarboxylase-deficient, m-hydroxybenzoate-nondegradable, and protocatechuate 4,5-dioxygenase-deficient mutants. Since one-step revertants of these mutants could utilize 4-hydroxyphthalate, the compound appears to be metabolized through m-hydroxybenzoate and protocatechuate in P. testosteroni NH1000.", "contents": "Phthalate and 4-hydroxyphthalate metabolism in Pseudomonas testosteroni: purification and properties of 4,5-dihydroxyphthalate decarboxylase. Phthalate is degraded through 4,5-dihydroxyphthalate and protocatechuate in Pseudomonas testosteroni NH1000. The ezyme 4,5-dihydroxyphthalate decarboxylase, catalyzing the conversion of 4,5-dihydroxyphthalate to protocatechuate and carbon dioxide, was purified approximately 130-fold from phthalate-induced cells of a protocatechuate 4,5-dioxygenase-deficient mutant of P. testosteroni. The most purified preparation showed a single protein band on sodium dodecyl sulfate-acrylamide disc gel electrophoresis with a molecular weight of 38,000. The apparent molecular weight of the native enzyme determined by Sephadex G-200 column chromatography was 150,000. Among the substrate analogs tested, only 4-hydroxyphthalate served as a substrate, which was decarboxylated to form m-hydroxybenzoate. The apparent Km values for 4,5-dihydroxyphthalate and 4-hydroxyphthalate were estimated to be 10.5 micrometer and 1.25 mM, respectively, and the Vmax for the former was 10 times larger than that for the latter. Whereas the wild-type strain could utilize 4-hydroxyphthalate as a sole source of carbon, none of the following could grow with the compound: 4,5-dihydroxyphthalate decarboxylase-deficient, m-hydroxybenzoate-nondegradable, and protocatechuate 4,5-dioxygenase-deficient mutants. Since one-step revertants of these mutants could utilize 4-hydroxyphthalate, the compound appears to be metabolized through m-hydroxybenzoate and protocatechuate in P. testosteroni NH1000."}
{"id": "PMID:29564", "title": "Tissue sterility in uneviscerated carcasses.", "content": "Sheep muscle tissue removed aseptically from control carcasses, from uneviscerated carcasses held at 20 degrees C for 24 h, and from carcasses of sheep subjected to stress before slaughter was examined for the presence of bacteria. All samples from a total of 68 carcasses were sterile. Whole-body autoradiography of mouse carcasses showed that 14C-labeled fixed bacteria injected after death remained in the lumen of the intestine. Live bacteria did not penetrate the mucosal surface until the tissue structure had been disrupted by proteolytic enzymes. Bacteria were unable to penetrate sections of intestine longitudinally until considerable structural breakdown had occurred, indicating that blood and lymph vessels do not normally offer a pathway for microbial invasion from the intestine. Clostridia, which have been reported to be responsible for deep spoilage of meat, reached maximum numbers 24 to 28 h after death in the intestines of guinea pig carcasses stored at 20 degrees C, but did not invade carcass tissues until the stomach ruptured as a result of proteolysis between 2 and 3 days after death.", "contents": "Tissue sterility in uneviscerated carcasses. Sheep muscle tissue removed aseptically from control carcasses, from uneviscerated carcasses held at 20 degrees C for 24 h, and from carcasses of sheep subjected to stress before slaughter was examined for the presence of bacteria. All samples from a total of 68 carcasses were sterile. Whole-body autoradiography of mouse carcasses showed that 14C-labeled fixed bacteria injected after death remained in the lumen of the intestine. Live bacteria did not penetrate the mucosal surface until the tissue structure had been disrupted by proteolytic enzymes. Bacteria were unable to penetrate sections of intestine longitudinally until considerable structural breakdown had occurred, indicating that blood and lymph vessels do not normally offer a pathway for microbial invasion from the intestine. Clostridia, which have been reported to be responsible for deep spoilage of meat, reached maximum numbers 24 to 28 h after death in the intestines of guinea pig carcasses stored at 20 degrees C, but did not invade carcass tissues until the stomach ruptured as a result of proteolysis between 2 and 3 days after death."}
{"id": "PMID:29565", "title": "Storage quality of dark, firm, dry meat.", "content": "Dark, firm, dry meat contains little or no glucose. Therefore, spoilage bacteria growing on such meat immediately attack amino acids so that spoilage odors and ammonia are detectable at comparatively low cell densities (about 10(6)/cm2).", "contents": "Storage quality of dark, firm, dry meat. Dark, firm, dry meat contains little or no glucose. Therefore, spoilage bacteria growing on such meat immediately attack amino acids so that spoilage odors and ammonia are detectable at comparatively low cell densities (about 10(6)/cm2)."}
{"id": "PMID:29566", "title": "Establishment of a heat inactivation curve for Clostridium botulinum 62A toxin in beef broth.", "content": "A procedure is described for establishing a heat inactivation curve for the toxin of Clostridium botulinum 62A in beef broth. The effect of toxin titer, pH, and the type of acid employed for pH adjustment on the heat stability of the toxin is described.", "contents": "Establishment of a heat inactivation curve for Clostridium botulinum 62A toxin in beef broth. A procedure is described for establishing a heat inactivation curve for the toxin of Clostridium botulinum 62A in beef broth. The effect of toxin titer, pH, and the type of acid employed for pH adjustment on the heat stability of the toxin is described."}
{"id": "PMID:29580", "title": "Membrane bound pyrophosphatases in Entamoeba histolytica.", "content": "Entamoeba histolytica homogenates are capable of hydrolyzing a range of inorganic and organic pyrophosphates. Two separate activities are present: an inorganic pyrophosphatase hydrolyzing inorganic pyrophosphate and linear tripolyphosphate, and a nucleoside diphosphatase hydrolyzing thiamine pyrophosphate and nucleoside diphosphates (ADP, GDP and UDP). The inorganic pyrophosphatase has an acid pH optimum, a relatively high KM (congurent to 1 micrometer) and is markedly heat stable and lacks a metal requirement. The nucleoside diphosphatase also has an acid pH optimum but displays a much higher affinity for substrate (KM congurent to 50 micrometer), is unstable to heating and is activated by Ca ions. Both pyrophosphatases distinct from the acid phosphatase activity which is also present. All three hydrolases are sedimentable and latent suggesting their association with membrane bounded organelles. No soluble inorganic pyrophosphatase activity could be demonstrated.", "contents": "Membrane bound pyrophosphatases in Entamoeba histolytica. Entamoeba histolytica homogenates are capable of hydrolyzing a range of inorganic and organic pyrophosphates. Two separate activities are present: an inorganic pyrophosphatase hydrolyzing inorganic pyrophosphate and linear tripolyphosphate, and a nucleoside diphosphatase hydrolyzing thiamine pyrophosphate and nucleoside diphosphates (ADP, GDP and UDP). The inorganic pyrophosphatase has an acid pH optimum, a relatively high KM (congurent to 1 micrometer) and is markedly heat stable and lacks a metal requirement. The nucleoside diphosphatase also has an acid pH optimum but displays a much higher affinity for substrate (KM congurent to 50 micrometer), is unstable to heating and is activated by Ca ions. Both pyrophosphatases distinct from the acid phosphatase activity which is also present. All three hydrolases are sedimentable and latent suggesting their association with membrane bounded organelles. No soluble inorganic pyrophosphatase activity could be demonstrated."}
{"id": "PMID:29585", "title": "Fine structural localization of alkaloid synthesis in endoplasmic reticulum of submerged Claviceps purpurea.", "content": "Acetyl coenzyme A (CoA) carboxylase (EC 6.4.1.2), an enzyme catalyzing the synthesis of malonyl-CoA, was cytochemically localized in endoplasmic reticulum (ER) of sclerotia-like cells of submerged Claviceps purpurea Tul. producing clavine alkaloids. The enzymic activity was structurally bound in unit membranes of ER strands which, later on, evolved into vacuoles containing lipoprotein material. The reaction product was absent from ER in nonvacuolized filamentous hyphae and ovoid asexual spores containing numerous lipid globules; it was also absent from ER in the mycelium of submerged C. purpurea strain producing no alkaloids. In view of our previous morphogenetic observations and the available biochemical evidence, the observed localization of acetyl-CoA carboxylase was assumed not to coincide with fatty acid biosynthesis but to represent sites of alkaloid synthesis.", "contents": "Fine structural localization of alkaloid synthesis in endoplasmic reticulum of submerged Claviceps purpurea. Acetyl coenzyme A (CoA) carboxylase (EC 6.4.1.2), an enzyme catalyzing the synthesis of malonyl-CoA, was cytochemically localized in endoplasmic reticulum (ER) of sclerotia-like cells of submerged Claviceps purpurea Tul. producing clavine alkaloids. The enzymic activity was structurally bound in unit membranes of ER strands which, later on, evolved into vacuoles containing lipoprotein material. The reaction product was absent from ER in nonvacuolized filamentous hyphae and ovoid asexual spores containing numerous lipid globules; it was also absent from ER in the mycelium of submerged C. purpurea strain producing no alkaloids. In view of our previous morphogenetic observations and the available biochemical evidence, the observed localization of acetyl-CoA carboxylase was assumed not to coincide with fatty acid biosynthesis but to represent sites of alkaloid synthesis."}
{"id": "PMID:29586", "title": "Evidence for an incomplete reductive carboxylic acid cycle in Methanobacterium thermoautotrophicum.", "content": "The involvement of reactions of the tricarboxylic acid cycle in autotrophic CO2 fixation in Methanobacterium thermoautotrophicum was investigated. The incorporation of succinate into glutamate (= alpha-ketoglutarate), aspartate (= oxaloacetate) and alanine (= pyruvate) was studied. The organism was grown on H2 plus CO2 at pH 6.5 in the presence of 1 mM [U-14C-]succinate. Significant amounts of the dicarboxylic acid were incorporated into cellular material under these conditions. Alanine, aspartate, and glutamate were isolated and their specific radioactivities were determined. Only glutamate was found to be labelled. Degradation of glutamate revealed that C-1 of glutamate was derived from CO2 and C-2--C-5 from succinate indicating that in M. thermoautotrophicum alpha-ketoglutarate is synthesized via reductive carboxylation of succinyl CoA. The finding that succinate was not incorporated into alanine and aspartate excludes that oxaloacetate and pyruvate are synthesized from alpha-ketoglutarate via isocitrate or citrate. This is taken as evidence that a complete reductive carboxylic acid cycle is not involved here in autotrophic CO2 fixation.", "contents": "Evidence for an incomplete reductive carboxylic acid cycle in Methanobacterium thermoautotrophicum. The involvement of reactions of the tricarboxylic acid cycle in autotrophic CO2 fixation in Methanobacterium thermoautotrophicum was investigated. The incorporation of succinate into glutamate (= alpha-ketoglutarate), aspartate (= oxaloacetate) and alanine (= pyruvate) was studied. The organism was grown on H2 plus CO2 at pH 6.5 in the presence of 1 mM [U-14C-]succinate. Significant amounts of the dicarboxylic acid were incorporated into cellular material under these conditions. Alanine, aspartate, and glutamate were isolated and their specific radioactivities were determined. Only glutamate was found to be labelled. Degradation of glutamate revealed that C-1 of glutamate was derived from CO2 and C-2--C-5 from succinate indicating that in M. thermoautotrophicum alpha-ketoglutarate is synthesized via reductive carboxylation of succinyl CoA. The finding that succinate was not incorporated into alanine and aspartate excludes that oxaloacetate and pyruvate are synthesized from alpha-ketoglutarate via isocitrate or citrate. This is taken as evidence that a complete reductive carboxylic acid cycle is not involved here in autotrophic CO2 fixation."}
{"id": "PMID:29588", "title": "Cellulose degradation and cellulase formation by Phialophora malorum.", "content": "The formation of cellulases and beta-glucosidase and their location in the fungus Phialophora malorum was studied on some different carbon sources. The cellulases were found to be partly cell-free and partly cell-bound during growth on cellulose and carboxymethyl-cellulose. Glucose and cellobiose repressed the cellulase formation but a low carboxymethylcellulase activity was measurable on the glucose-grown mycelium. The unicellular stage did not appear to grow on carboxymethyl-cellulose or cellulose, but mycelium was formed on these carbon sources.", "contents": "Cellulose degradation and cellulase formation by Phialophora malorum. The formation of cellulases and beta-glucosidase and their location in the fungus Phialophora malorum was studied on some different carbon sources. The cellulases were found to be partly cell-free and partly cell-bound during growth on cellulose and carboxymethyl-cellulose. Glucose and cellobiose repressed the cellulase formation but a low carboxymethylcellulase activity was measurable on the glucose-grown mycelium. The unicellular stage did not appear to grow on carboxymethyl-cellulose or cellulose, but mycelium was formed on these carbon sources."}
{"id": "PMID:29589", "title": "Incorporation of labeled small molecules into rubratoxin.", "content": "A sterile glucose-mineral salts broth was inoculated with conidia of Penicillium rubrum P-13 and P-3290. Radiolabeled compounds were added to some cultures, these being incubated quiescently at 28 degrees C for 14 days. Other stationary cultures were grown for 21 days, received labeled compounds, and were then grown for 5 more days. The remaining cultures were inoculated with 72-h-old mycelial pellets, received labeled materials and were incubated with shaking for 60 h. Rubratoxin was resolved by thin-layer chromatography. Labeled [1(14)C]acetate, [1,5(14)C]citrate, [2(14)C]malonate, [1(14)C]glucose, [U14C]glucose or [1(14)C]hexanoate were incorporated into rubratoxins A and B by P. rubrum 3290 and into rubratoxin B by P. rubrum 13. Incorporation of [1(14)C]acetate and [2(14)C]malonate increased when exogenous unlabeled acetate, malonate, pyruvate, or phosphoenol-pyruvate was added. Acetate incorporation was influenced by cultural conditions, attaining maximum amounts in quiescent cultures which received labeled acetate after 21 days of incubation. Acetate incorporation in shake cultures was enhanced by reduced nicotinamide adenine dinucleotide phosphate (NADPH) and by unlabeled exogenous citrate.", "contents": "Incorporation of labeled small molecules into rubratoxin. A sterile glucose-mineral salts broth was inoculated with conidia of Penicillium rubrum P-13 and P-3290. Radiolabeled compounds were added to some cultures, these being incubated quiescently at 28 degrees C for 14 days. Other stationary cultures were grown for 21 days, received labeled compounds, and were then grown for 5 more days. The remaining cultures were inoculated with 72-h-old mycelial pellets, received labeled materials and were incubated with shaking for 60 h. Rubratoxin was resolved by thin-layer chromatography. Labeled [1(14)C]acetate, [1,5(14)C]citrate, [2(14)C]malonate, [1(14)C]glucose, [U14C]glucose or [1(14)C]hexanoate were incorporated into rubratoxins A and B by P. rubrum 3290 and into rubratoxin B by P. rubrum 13. Incorporation of [1(14)C]acetate and [2(14)C]malonate increased when exogenous unlabeled acetate, malonate, pyruvate, or phosphoenol-pyruvate was added. Acetate incorporation was influenced by cultural conditions, attaining maximum amounts in quiescent cultures which received labeled acetate after 21 days of incubation. Acetate incorporation in shake cultures was enhanced by reduced nicotinamide adenine dinucleotide phosphate (NADPH) and by unlabeled exogenous citrate."}
{"id": "PMID:29590", "title": "Utilization of D-amino acids by dadR mutants of Salmonella typhimurium.", "content": "Utilization of D-amino acids being substrates of D-amino acid dehydrogenase of Salmonella typhimurium was examined. The experiments were done with wild type strains and the mutants dadA missing the enzyme activity and dadR in which its synthesis is released from catabolite repression. Growth on D-tryptophan, D-histidine and D-methionine used as precursors of the L-amino acids was faster when the respective auxotrophs carried dadR mutations. The dadR mutants grew faster when D-or L-alanine was present as a sole source of nitrogen. Experiments with D-amino acid dehydrogenase in vitro provided evidence that D-tryptophan is its substrate with a very low affinity to the dehydrogenase.", "contents": "Utilization of D-amino acids by dadR mutants of Salmonella typhimurium. Utilization of D-amino acids being substrates of D-amino acid dehydrogenase of Salmonella typhimurium was examined. The experiments were done with wild type strains and the mutants dadA missing the enzyme activity and dadR in which its synthesis is released from catabolite repression. Growth on D-tryptophan, D-histidine and D-methionine used as precursors of the L-amino acids was faster when the respective auxotrophs carried dadR mutations. The dadR mutants grew faster when D-or L-alanine was present as a sole source of nitrogen. Experiments with D-amino acid dehydrogenase in vitro provided evidence that D-tryptophan is its substrate with a very low affinity to the dehydrogenase."}
{"id": "PMID:29592", "title": "Relation of plasma prolactin to clinical response in schizophrenic patients.", "content": "It has been suggested that, if dopamine antagonism is a necessary condition for the antischizophrenic action of neuroleptics, the prolactin response, as an index of dopamine blockade, would correlate with clinical response. Morning prolactin and clinical symptomatology were measured in 15 schizophrenic patients before neuroleptic therapy, and after three and six weeks of high-dose butaperazine or loxapine treatment. Prolactin levels were transiently elevated during the unmedicated admission period, probably reflecting a normal stress response. Prolactin increased in all patients during neuroleptic therapy. There was, however, no correlation between magnitude of prolactin changes and clinical response, probably because the prolactin response achieved a maximum at relatively low doses of neuroleptics.", "contents": "Relation of plasma prolactin to clinical response in schizophrenic patients. It has been suggested that, if dopamine antagonism is a necessary condition for the antischizophrenic action of neuroleptics, the prolactin response, as an index of dopamine blockade, would correlate with clinical response. Morning prolactin and clinical symptomatology were measured in 15 schizophrenic patients before neuroleptic therapy, and after three and six weeks of high-dose butaperazine or loxapine treatment. Prolactin levels were transiently elevated during the unmedicated admission period, probably reflecting a normal stress response. Prolactin increased in all patients during neuroleptic therapy. There was, however, no correlation between magnitude of prolactin changes and clinical response, probably because the prolactin response achieved a maximum at relatively low doses of neuroleptics."}
{"id": "PMID:29593", "title": "Monozygotic twins with presumed metachromatic leukodystrophy. Activity of arylsulfatase A in serum of patients and family.", "content": "Arylsulfatase A (ASA) activity in urine and serum was assayed on two 21-month-old monozygotic twins with presumed metachromatic leukodystrophy (MLD), their parents, and kin. The patients showed a marked reduction in ASA activity in both urine and serum. The twins' parents and 11 kin, a total of 13 persons, were examined for ASA activity in serum, but it was not possible to delineate heterozygous carriers of MLD by the present study. The assay of ASA activity in serum promises to be useful for diagnosis of MLD.", "contents": "Monozygotic twins with presumed metachromatic leukodystrophy. Activity of arylsulfatase A in serum of patients and family. Arylsulfatase A (ASA) activity in urine and serum was assayed on two 21-month-old monozygotic twins with presumed metachromatic leukodystrophy (MLD), their parents, and kin. The patients showed a marked reduction in ASA activity in both urine and serum. The twins' parents and 11 kin, a total of 13 persons, were examined for ASA activity in serum, but it was not possible to delineate heterozygous carriers of MLD by the present study. The assay of ASA activity in serum promises to be useful for diagnosis of MLD."}
{"id": "PMID:29597", "title": "Behavior therapy and the treatment of flight phobia.", "content": "Research since 1960 was reviewed to compare the relative efficacy of behavior therapy and other therapy modalities in the treatment of flight phobias in trained military aircrew, commercial flight crews, and civilian air travellers. Results indicated that treatment programs involving behavior therapy techniques appeared to have a higher success rate than treatment programs not involving these techniques, especially in cases of focal fear with acute onset under stressful conditions. Other conditions for optimal outcome are outlined and hypotheses for a more programmatic research effort discussed.", "contents": "Behavior therapy and the treatment of flight phobia. Research since 1960 was reviewed to compare the relative efficacy of behavior therapy and other therapy modalities in the treatment of flight phobias in trained military aircrew, commercial flight crews, and civilian air travellers. Results indicated that treatment programs involving behavior therapy techniques appeared to have a higher success rate than treatment programs not involving these techniques, especially in cases of focal fear with acute onset under stressful conditions. Other conditions for optimal outcome are outlined and hypotheses for a more programmatic research effort discussed."}
{"id": "PMID:29601", "title": "Purification and properties of gamma-glutamylcyclotransferase from human erythrocytes.", "content": "1. GAMMA-Glutamylcyclotransferase was purified 10000-fold from human erythrocytes. 2. The purification steps involved fractionation with (NH4)(2)SO(4) and chromatography on Sephadex G-75, DEAE-cellulose and hydroxyapatite. The purified enzyme was found to be homogeneous on density-gradient polyacrylamide-gel electrophoresis. 3. The maximum reaction rate was observed at pH9.0 and the apparent Km value for gamma-glutamyl-L-alanine was 2.2mM. 4. The molecular weight (25250) of the purified enzyme agreed well with the value (25500) in fresh haemolysates, indicating no apparent structural modification of the enzyme during purification. However, rapid processing of the blood through the initial (NH4)(2)SO(4) and Sephadex-chromatography steps was required to prevent formation of a high-molecular-weight aggregate with substantially lower specific activity. 5. gamma-Glutamylcyclotransferase catalyses the formation of 5-oxoproline from gamma-glutamyl dipeptides. The role of this enzyme in erythrocytes is of particular interest, because gamma-glutamyl-L-cysteine serves as a substrate for both gamma-glutamylcyclotransferase and glutathione synthetase. Thus the cyclotransferase could modulate glutathione synthesis.", "contents": "Purification and properties of gamma-glutamylcyclotransferase from human erythrocytes. 1. GAMMA-Glutamylcyclotransferase was purified 10000-fold from human erythrocytes. 2. The purification steps involved fractionation with (NH4)(2)SO(4) and chromatography on Sephadex G-75, DEAE-cellulose and hydroxyapatite. The purified enzyme was found to be homogeneous on density-gradient polyacrylamide-gel electrophoresis. 3. The maximum reaction rate was observed at pH9.0 and the apparent Km value for gamma-glutamyl-L-alanine was 2.2mM. 4. The molecular weight (25250) of the purified enzyme agreed well with the value (25500) in fresh haemolysates, indicating no apparent structural modification of the enzyme during purification. However, rapid processing of the blood through the initial (NH4)(2)SO(4) and Sephadex-chromatography steps was required to prevent formation of a high-molecular-weight aggregate with substantially lower specific activity. 5. gamma-Glutamylcyclotransferase catalyses the formation of 5-oxoproline from gamma-glutamyl dipeptides. The role of this enzyme in erythrocytes is of particular interest, because gamma-glutamyl-L-cysteine serves as a substrate for both gamma-glutamylcyclotransferase and glutathione synthetase. Thus the cyclotransferase could modulate glutathione synthesis."}
{"id": "PMID:29602", "title": "Purification of rat intestinal maltase/glucoamylase and its anomalous dissociation either by heat or by low pH.", "content": "Maltase-glucoamylase, a microvillous membrane ectoenzyme, was solubilized from rat intestinal mucosa by digestion with papain and subsequently purified to homogeneity with an overall yield of 10--20%. An antibody to the purified enzyme formed a single precipitin line in immunodiffusion experiments with an intestinal homogenate. The enzyme was shown to be an acidic glycoprotein (20% sugar by weight) which contained low amounts of cysteine and no sialic acid. At pH3--6, maltase activity was slowly lost, but the enzyme was re-activated by re-adjustment of the pH to neutrality. However, in the presence of sodium dodecyl sulphate, acid pH values inactivated maltase irreversibly, and at the same time converted the enzyme (mol.wt. 500000 approx.) into five new species with apparent molecular weights ranging from 134000 to 480000 as judged by polyacrylamide-gel electrophoresis. The same five fragments were also formed by boiling the enzyme for brief periods in the presence of sodium dodecyl sulphate or urea either with or without reducing agents. The dissociated species were stable on re-electrophoresis, and amino acid analysis showed them to be very similar to each other and to the original enzyme. The bands migrated anomalously on polyacrylamide gels of different concentration, thereby preventing the assignment of precise molecular weights. It is possible that the five species may represent stable aggregates of a common monomer of the enzyme.", "contents": "Purification of rat intestinal maltase/glucoamylase and its anomalous dissociation either by heat or by low pH. Maltase-glucoamylase, a microvillous membrane ectoenzyme, was solubilized from rat intestinal mucosa by digestion with papain and subsequently purified to homogeneity with an overall yield of 10--20%. An antibody to the purified enzyme formed a single precipitin line in immunodiffusion experiments with an intestinal homogenate. The enzyme was shown to be an acidic glycoprotein (20% sugar by weight) which contained low amounts of cysteine and no sialic acid. At pH3--6, maltase activity was slowly lost, but the enzyme was re-activated by re-adjustment of the pH to neutrality. However, in the presence of sodium dodecyl sulphate, acid pH values inactivated maltase irreversibly, and at the same time converted the enzyme (mol.wt. 500000 approx.) into five new species with apparent molecular weights ranging from 134000 to 480000 as judged by polyacrylamide-gel electrophoresis. The same five fragments were also formed by boiling the enzyme for brief periods in the presence of sodium dodecyl sulphate or urea either with or without reducing agents. The dissociated species were stable on re-electrophoresis, and amino acid analysis showed them to be very similar to each other and to the original enzyme. The bands migrated anomalously on polyacrylamide gels of different concentration, thereby preventing the assignment of precise molecular weights. It is possible that the five species may represent stable aggregates of a common monomer of the enzyme."}
{"id": "PMID:29603", "title": "The selective retardation of NADP+-dependent dehydrogenases by immobilized procion red HE-3B.", "content": "The capacities of Procion Red HE-3B and Cibacron Blue F3G-A immobilized to Sepharose CL-4B and Matrex 201R for NAD+-, NADP+- and NAD(P)+-dependent dehydrogenases were measured. Procion Red HE-3B columns retarded NADP+-dependent dehydrogenases more effectively than NAD+-dependent dehydrogenases, whilst immobilized Cibacron Blue F3G-A retarded NAD+-dependent dehydrogenases more effectively than NADP+-dependent dehydrogenases. The capacity of procion Red HE-3B-Sepharose CL-4B for five dehydrogenases was highest in the region of 70nmol of immobilized ligand/ml of settled gel. The effects of using poly(ethyleneimine) as a spacer for both porous and pellicular supports were also examined. Four NADP+-dependent dehydrogenases were purified from yeast extract by using Procion Red HE-3B-Sepharose CL-4B. Two NAD+-dependent dehydrogenases were purified from the same source using Cibacron Blue F3G-A-Sepharose CL-4B. These results are discussed in relation to the use of immobilized Procion Red HE-3B to purify dehydrogenases. This immobilized dye's chromatograhic behaviour is compared with that of immobilized nucleotides. The most important feature of immobilized tirazine dyes seems to be their high operational capacities when compared with group-specific nucleotide adsorbents.", "contents": "The selective retardation of NADP+-dependent dehydrogenases by immobilized procion red HE-3B. The capacities of Procion Red HE-3B and Cibacron Blue F3G-A immobilized to Sepharose CL-4B and Matrex 201R for NAD+-, NADP+- and NAD(P)+-dependent dehydrogenases were measured. Procion Red HE-3B columns retarded NADP+-dependent dehydrogenases more effectively than NAD+-dependent dehydrogenases, whilst immobilized Cibacron Blue F3G-A retarded NAD+-dependent dehydrogenases more effectively than NADP+-dependent dehydrogenases. The capacity of procion Red HE-3B-Sepharose CL-4B for five dehydrogenases was highest in the region of 70nmol of immobilized ligand/ml of settled gel. The effects of using poly(ethyleneimine) as a spacer for both porous and pellicular supports were also examined. Four NADP+-dependent dehydrogenases were purified from yeast extract by using Procion Red HE-3B-Sepharose CL-4B. Two NAD+-dependent dehydrogenases were purified from the same source using Cibacron Blue F3G-A-Sepharose CL-4B. These results are discussed in relation to the use of immobilized Procion Red HE-3B to purify dehydrogenases. This immobilized dye's chromatograhic behaviour is compared with that of immobilized nucleotides. The most important feature of immobilized tirazine dyes seems to be their high operational capacities when compared with group-specific nucleotide adsorbents."}
{"id": "PMID:29604", "title": "Malate dehydrogenase of the cytosol. Ionizations of the enzyme-reduced-coenzyme complex and a comparison with lactate dehydrogenase.", "content": "1. The pH-dependencies of the binding of NADH and reduced nicotinamide--benzimidazole dinucleotide to pig heart cytoplasmic malate dehydrogenase and lactate dehydrogenase are reported. 2. Two ionizing groups were observed in the binding of both reduced coenzymes to lactate dehydrogenase. One group, with pKa in the range 6.3--6.7, is the active-site histidine residue and its deprotonation weakens binding of reduced coenzyme 3-fold. Binding of both coenzymes is decreased to zero when a second group, of pKa 8.9, deprotonates. This group is not cysteine-165.3. Only one ionization is required to characterize the binding of the two reduced coenzymes to malate dehydrogenase. The group involved appears to be the active-site histidine residue, since its ethoxycarbonylation inhibits the enzyme and abolishes binding of reduced coenzyme. Binding of either reduced coenzyme increases the pKa of the group from 6.4 to 7.4, and deprotonation of the group is accompanied by a 10-fold weakening of coenzyme binding. 4. Two reactive histidine residues were detected per malate dehydrogenase dimer. 5. A mechanism which emphasizes the homology between the two enzymes is presented.", "contents": "Malate dehydrogenase of the cytosol. Ionizations of the enzyme-reduced-coenzyme complex and a comparison with lactate dehydrogenase. 1. The pH-dependencies of the binding of NADH and reduced nicotinamide--benzimidazole dinucleotide to pig heart cytoplasmic malate dehydrogenase and lactate dehydrogenase are reported. 2. Two ionizing groups were observed in the binding of both reduced coenzymes to lactate dehydrogenase. One group, with pKa in the range 6.3--6.7, is the active-site histidine residue and its deprotonation weakens binding of reduced coenzyme 3-fold. Binding of both coenzymes is decreased to zero when a second group, of pKa 8.9, deprotonates. This group is not cysteine-165.3. Only one ionization is required to characterize the binding of the two reduced coenzymes to malate dehydrogenase. The group involved appears to be the active-site histidine residue, since its ethoxycarbonylation inhibits the enzyme and abolishes binding of reduced coenzyme. Binding of either reduced coenzyme increases the pKa of the group from 6.4 to 7.4, and deprotonation of the group is accompanied by a 10-fold weakening of coenzyme binding. 4. Two reactive histidine residues were detected per malate dehydrogenase dimer. 5. A mechanism which emphasizes the homology between the two enzymes is presented."}
{"id": "PMID:29605", "title": "Identification of histidine-122alpha in human haemoglobin as one of the unknown alkaline Bohr groups by hydrogen--tritium exchange.", "content": "Human carbonmonoxy- and deoxy-haemoglobins were incubated at 37 degrees C in 3H2O at various pH values to measure the pH-dependent hydrogen--tritium exchange at the C-2 position of the imidazole ring of histidine-122alpha. To obtain the pseudo-first-order rate constants for the exchange, k, the two peptides containing histidine-122alpha were isolated and the amounts of tritium incorporated were determined. The rate constants gave pK values for the histidine of 6.1 in carbonmonoxyhaemoglobin and 6.6 in deoxyhaemoglobin, showing that it contributes about 20% to the total alkaline Bohr effect and about 10% at pH7.4.", "contents": "Identification of histidine-122alpha in human haemoglobin as one of the unknown alkaline Bohr groups by hydrogen--tritium exchange. Human carbonmonoxy- and deoxy-haemoglobins were incubated at 37 degrees C in 3H2O at various pH values to measure the pH-dependent hydrogen--tritium exchange at the C-2 position of the imidazole ring of histidine-122alpha. To obtain the pseudo-first-order rate constants for the exchange, k, the two peptides containing histidine-122alpha were isolated and the amounts of tritium incorporated were determined. The rate constants gave pK values for the histidine of 6.1 in carbonmonoxyhaemoglobin and 6.6 in deoxyhaemoglobin, showing that it contributes about 20% to the total alkaline Bohr effect and about 10% at pH7.4."}
{"id": "PMID:29606", "title": "Sequential deiodination of thyroxine in rat liver homogenate.", "content": "Rat liver homogenate was incubated at 37 degrees C with thyroxine, 3,3',5-tri-iodothyronine, 3,3',5'-tri-iodothyronine or 3,3'-di-iodothyronine. The degradation or accumulation of these compounds was measured by specific radioimmunoassays. (1) Production of 3,3',5-tri-iodothyronine from thyroxine was highest at pH 6.0--6.5 and was markedly stimulated by the addition of dithiothreitol and effectively inhibited in the presence of 6-propyl-2-thiouracil. (2) Accumulation of 3,3',5'-tri-iodothyronine on incubation of thyroxine with homogenate was only observed above pH 8.5. Otherwise the product was converted into 3,3'-di-iodothyronine too rapidly to allow its measurement. By measuring 3,3'-di-iodothyronine it was deduced that 5-deiodination of thyroxine was most effective at approx. pH 8.0. Dithiothreitol powerfully stimulated this reaction and 6-propyl-2-thiouracil strongly inhibited. (3) Monodeiodination of the tyrosine ring of 3,3',5-tri-iodothyronine was the slowest reaction, was optimal at pH 8.0 and was less affected by dithiothreitol and 6-propyl-2-thiouracil than the above reactions. (4) 5'-Deiodination of 3,3',5'-tri-iodothyronine was extremely rapid, with a pH optimum probably at about 6.5. Owing to the high reaction rate under the conditions used it was not possible to assess the effects of dithiothreitol and 6-propyl-2-thiouracil.", "contents": "Sequential deiodination of thyroxine in rat liver homogenate. Rat liver homogenate was incubated at 37 degrees C with thyroxine, 3,3',5-tri-iodothyronine, 3,3',5'-tri-iodothyronine or 3,3'-di-iodothyronine. The degradation or accumulation of these compounds was measured by specific radioimmunoassays. (1) Production of 3,3',5-tri-iodothyronine from thyroxine was highest at pH 6.0--6.5 and was markedly stimulated by the addition of dithiothreitol and effectively inhibited in the presence of 6-propyl-2-thiouracil. (2) Accumulation of 3,3',5'-tri-iodothyronine on incubation of thyroxine with homogenate was only observed above pH 8.5. Otherwise the product was converted into 3,3'-di-iodothyronine too rapidly to allow its measurement. By measuring 3,3'-di-iodothyronine it was deduced that 5-deiodination of thyroxine was most effective at approx. pH 8.0. Dithiothreitol powerfully stimulated this reaction and 6-propyl-2-thiouracil strongly inhibited. (3) Monodeiodination of the tyrosine ring of 3,3',5-tri-iodothyronine was the slowest reaction, was optimal at pH 8.0 and was less affected by dithiothreitol and 6-propyl-2-thiouracil than the above reactions. (4) 5'-Deiodination of 3,3',5'-tri-iodothyronine was extremely rapid, with a pH optimum probably at about 6.5. Owing to the high reaction rate under the conditions used it was not possible to assess the effects of dithiothreitol and 6-propyl-2-thiouracil."}
{"id": "PMID:29607", "title": "Factors affecting the activity of guanylate cyclase in lysates of human blood platelets.", "content": "1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by contaminating soluble enzyme, suggesting that physiological aggregating agents may increase cyclic GMP in intact platelets through the effects of intermediary factors. The activated and inhibited states of the enzyme described in the present paper may be relevant to the actions of these factors.", "contents": "Factors affecting the activity of guanylate cyclase in lysates of human blood platelets. 1. Under optimal ionic conditions (4 mM-MnCl2) the specific activity of guanylate cyclase in fresh platelet lysates was about 10nmol of cyclic GMP formed/20 min per mg of protein at 30 degrees C. Activity was 15% of optimum with 10mM-MgCl2 and negligible with 4mM-CaCl2. Synergism between MnCl2 and MgCl2 or CaCl2 was observed when [MnCl2] less than or equal to [GPT]. 2. Lower than optimal specific activities were obtained in assays containing large volumes of platelet lysate, owing to the presence of inhibitory factors that could be removed by ultrafiltration. Adenine nucleotides accounted for less than 50% of the inhibitory activity. 3. Preincubation of lysate for 1 h at 30 degrees C increased the specific activity of platelet guanylate cyclase by about 2-fold. 4. Lubrol PX (1%, w/v) stimulated guanylate cyclase activity by 3--5-fold before preincubation and by about 2-fold after preincubation. Triton X-100 was much less effective. 5. Dithiothreitol inhibited the guanylate cyclase activity of untreated, preincubated and Lubrol PX-treated lysates and prevented activation by preincubation provided that it was added beforehand. 6. Oleate stimulated guanylate cyclase activity 3--4-fold and arachidonate 2--3-fold, whereas palmitate was almost inactive. Pretreatment of lysate with indomethacin did not inhibit this effect of arachidonate. Oleate and arachidonate caused marked stimulation of guanylate cyclase in preincubated lysate, but inhibited the enzyme in Lubrol PX-treated lysate. 7. NaN3 (10mM) increased guanylate cyclase activity by up to 7-fold; this effect was both time- and temperature-dependent. NaN3 did not further activate the enzyme in Lubrol PX-treated lysate. 8. The results indicated that preincubation, Lubrol PX, fatty acids and NaN3 activated platelet guanylate cyclase by different mechanisms. 9. Platelet particulate fractions contained no guanylate cyclase activity detectable in the presence or absence of Lubrol PX that could not be accounted for by contaminating soluble enzyme, suggesting that physiological aggregating agents may increase cyclic GMP in intact platelets through the effects of intermediary factors. The activated and inhibited states of the enzyme described in the present paper may be relevant to the actions of these factors."}
{"id": "PMID:29608", "title": "Subcellular distribution of glycosidases in human polymorphonuclear leucocytes.", "content": "The subcellular distribution of nine glycosidases were studied in fractions of homogenized human polymorphonuclear leucocytes (neutrophils) obtained by isopycnic centrifugation through linear sucrose density gradients. The substrates were 4-methylumbelliferyl glycosides. All nine glycosides were hydrolysed by enzymes in neutrophil cytosol fractions, and by enzymes in at least one granule population. alpha-Glucosidase activity sedimented in sucrose density gradients to a point (p = 1.180 g/ml) just above the specific granules, possibly the 'tertiary' granule population. The peak corresponding to alpha-glucosidase did not co-sediment with, but considerably overlapped, the peak corresponding to lactoferrin, a marker for specific granules (p = 1.187 g/ml). alpha-Galactosidase activity was found primarily in heavy azurophil granules (p = 1.222 g/ml). alpha-Mannosidase activity was found primarily in light azurophil granules (p = 1.206 g/ml), following the distribution of myeloperoxidase, the commonly used azurophil granule marker. beta-Glucosidase activity was concentrated in mitochondrial fractions (p = 1.160 g/ml). All other glycosidases presented complex distributions, with activities not restricted to one granule class. Granule-associated glycosidase activities were increased 2--38 times when measured in the presence of 0.05% Triton X-100, indicating latency of the enzymes within granules.", "contents": "Subcellular distribution of glycosidases in human polymorphonuclear leucocytes. The subcellular distribution of nine glycosidases were studied in fractions of homogenized human polymorphonuclear leucocytes (neutrophils) obtained by isopycnic centrifugation through linear sucrose density gradients. The substrates were 4-methylumbelliferyl glycosides. All nine glycosides were hydrolysed by enzymes in neutrophil cytosol fractions, and by enzymes in at least one granule population. alpha-Glucosidase activity sedimented in sucrose density gradients to a point (p = 1.180 g/ml) just above the specific granules, possibly the 'tertiary' granule population. The peak corresponding to alpha-glucosidase did not co-sediment with, but considerably overlapped, the peak corresponding to lactoferrin, a marker for specific granules (p = 1.187 g/ml). alpha-Galactosidase activity was found primarily in heavy azurophil granules (p = 1.222 g/ml). alpha-Mannosidase activity was found primarily in light azurophil granules (p = 1.206 g/ml), following the distribution of myeloperoxidase, the commonly used azurophil granule marker. beta-Glucosidase activity was concentrated in mitochondrial fractions (p = 1.160 g/ml). All other glycosidases presented complex distributions, with activities not restricted to one granule class. Granule-associated glycosidase activities were increased 2--38 times when measured in the presence of 0.05% Triton X-100, indicating latency of the enzymes within granules."}
{"id": "PMID:29653", "title": "Effect of diuretic, beta-adrenoceptor blocking agent and their combination on elevated blood pressure and serum potassium: a cross-over study.", "content": "1. The antihypertensive effect of a new beta-adrenoceptor blocking agent, trimepranol (10--14 mg/twice daily), chlorthalidone (50 mg every second day) and their combination was studied in eighteen patients with mild to moderate essential hypertension. In a controlled randomized cross-over study the drugs were given for 6 week periods. 2. A significant and equal decrease in blood pressure was achieved both with trimepranol and chlorthalidone, whereas their combination was significantly more effective. 3. Trimepranol significantly antagonized the chlorthalidone-induced hypokalemia. 4. The results favor the use of diuretic or diuretic-beta-adrenoceptor blocker combination over beta-adrenoceptor blocker monotherapy in the treatment of mild to moderate hypertension.", "contents": "Effect of diuretic, beta-adrenoceptor blocking agent and their combination on elevated blood pressure and serum potassium: a cross-over study. 1. The antihypertensive effect of a new beta-adrenoceptor blocking agent, trimepranol (10--14 mg/twice daily), chlorthalidone (50 mg every second day) and their combination was studied in eighteen patients with mild to moderate essential hypertension. In a controlled randomized cross-over study the drugs were given for 6 week periods. 2. A significant and equal decrease in blood pressure was achieved both with trimepranol and chlorthalidone, whereas their combination was significantly more effective. 3. Trimepranol significantly antagonized the chlorthalidone-induced hypokalemia. 4. The results favor the use of diuretic or diuretic-beta-adrenoceptor blocker combination over beta-adrenoceptor blocker monotherapy in the treatment of mild to moderate hypertension."}
{"id": "PMID:29654", "title": "Pleuropulmonary lung infection by anaerobic bacteria.", "content": "Two patients with severe pleuropulmonary infection caused by non-sporing anaerobic bacteria are described. One had an empyema with foul-smelling pus and developed bacteraemia, and the other developed a lung abscess. Both were successfully treated with antibiotics and drainage, chest surgery being avoided. The successful diagnosis and treatment of these patients involved close liaison between clinical and laboratory staff.", "contents": "Pleuropulmonary lung infection by anaerobic bacteria. Two patients with severe pleuropulmonary infection caused by non-sporing anaerobic bacteria are described. One had an empyema with foul-smelling pus and developed bacteraemia, and the other developed a lung abscess. Both were successfully treated with antibiotics and drainage, chest surgery being avoided. The successful diagnosis and treatment of these patients involved close liaison between clinical and laboratory staff."}
{"id": "PMID:29656", "title": "Continuous measurement of tissue pH in the human fetal scalp.", "content": "A method for continuous measurement of scalp tissue pH is described. The tissue pH probe was found to be robust and values for tissue pH were close to those for scalp blood pH. Combining the pH and fetal heart fate (FHR) electrodes in the one mechanical assembly facilitated application to the fetal scalp in early labour but the combined assembly electrode was found to have some disadvantages and manufacture of a separate tissue PH electrode is recommended. Continuous monitoring of scalp tissue pH enables closer study of the physiological basis of changes in fetal acid base status and should prove useful to the obstetrician in management of high risk pregnancies during labour.", "contents": "Continuous measurement of tissue pH in the human fetal scalp. A method for continuous measurement of scalp tissue pH is described. The tissue pH probe was found to be robust and values for tissue pH were close to those for scalp blood pH. Combining the pH and fetal heart fate (FHR) electrodes in the one mechanical assembly facilitated application to the fetal scalp in early labour but the combined assembly electrode was found to have some disadvantages and manufacture of a separate tissue PH electrode is recommended. Continuous monitoring of scalp tissue pH enables closer study of the physiological basis of changes in fetal acid base status and should prove useful to the obstetrician in management of high risk pregnancies during labour."}
{"id": "PMID:29657", "title": "The level and origin of amylase (EC 3.2.1.1) in the digestive tract of chicks receiving trypsin inhibitors in their diet.", "content": "1. Amylase (EC 3.2.1.1) activity found in the intestinal tract of chicks posterior to the stomach is of endogenous origin, as amylase in the food is inactivated by the low pH in the stomachs. 2. Ingestion of raw soya-bean diet (RSD) or of heated soya-bean diet (HSD) supplemented with trypsin inhibitors induced higher amylase activites in the lower part of the small intestine and caecum as compared with HSD. 3. Ingestion of RSD after ligation at the end of the duodenum, end of the ileum or one of the cacea, or injection of soya-bean trypsin inhibitor into a aligated caecum, indicated that there is no amylase synthesis by the intestinal tract cells or microflora as a response to the presence of RSD or trypsin inhibitors. 4. It seems that amylase found in the digestive tract of the chick is of pancreatic origin and the RSD or trypsin inhibitors induce higher pancreatic amylase secretion than HSD which (the additiona amylase) accumulates mainly in the caeca.", "contents": "The level and origin of amylase (EC 3.2.1.1) in the digestive tract of chicks receiving trypsin inhibitors in their diet. 1. Amylase (EC 3.2.1.1) activity found in the intestinal tract of chicks posterior to the stomach is of endogenous origin, as amylase in the food is inactivated by the low pH in the stomachs. 2. Ingestion of raw soya-bean diet (RSD) or of heated soya-bean diet (HSD) supplemented with trypsin inhibitors induced higher amylase activites in the lower part of the small intestine and caecum as compared with HSD. 3. Ingestion of RSD after ligation at the end of the duodenum, end of the ileum or one of the cacea, or injection of soya-bean trypsin inhibitor into a aligated caecum, indicated that there is no amylase synthesis by the intestinal tract cells or microflora as a response to the presence of RSD or trypsin inhibitors. 4. It seems that amylase found in the digestive tract of the chick is of pancreatic origin and the RSD or trypsin inhibitors induce higher pancreatic amylase secretion than HSD which (the additiona amylase) accumulates mainly in the caeca."}
{"id": "PMID:29659", "title": "Critical ionization states in the reaction catalyzed by triosephosphate isomerase.", "content": "To allow the detailed interpretation of the pH dependences of the steady-state parameters for the reaction catalyzed by triosephosphate isomerase, three kinds of experiments have been performed. First, the value of kcat/Km for enzyme-catalyzed isomerization of the phosphonate analogue of D-glyceraldehyde 3-phosphate (2-hydroxy-4-phosphonobutyraldehyde) has been shown to titrate with an apparent pKa of 7.5, which is close to the phosphonate's second ionization constant. Secondly, the sulfate ester analogue of dihydroxyacetone phosphate (dihydroxyacetone sulfate), which exists only as a monoanion over the pH range of interest, has been shown not to bind detectably to the enzyme. Thirdly, an isotopic discrimination experiment at pH 5.2 has been compared with a similar investigation at pH 7.6. The results together demonstrate that both enzyme and substrate ionizations control the reaction rate in the pH range 5 to 8.", "contents": "Critical ionization states in the reaction catalyzed by triosephosphate isomerase. To allow the detailed interpretation of the pH dependences of the steady-state parameters for the reaction catalyzed by triosephosphate isomerase, three kinds of experiments have been performed. First, the value of kcat/Km for enzyme-catalyzed isomerization of the phosphonate analogue of D-glyceraldehyde 3-phosphate (2-hydroxy-4-phosphonobutyraldehyde) has been shown to titrate with an apparent pKa of 7.5, which is close to the phosphonate's second ionization constant. Secondly, the sulfate ester analogue of dihydroxyacetone phosphate (dihydroxyacetone sulfate), which exists only as a monoanion over the pH range of interest, has been shown not to bind detectably to the enzyme. Thirdly, an isotopic discrimination experiment at pH 5.2 has been compared with a similar investigation at pH 7.6. The results together demonstrate that both enzyme and substrate ionizations control the reaction rate in the pH range 5 to 8."}
{"id": "PMID:29660", "title": "Exchange mechanisms for hydrogen bonding protons of cytidylic and guanylic acids.", "content": "The pH dependence of buffer catalysis of exchange of the C-4 amino protons of cyclic cytosine 2',3'-monophosphate (cCMP) and the N-1 proton of cyclic guanosine 2',3'-monophosphate (cGMP) conforms to an exchange mechanism, in which protonation of the nucleobases at C(N-3) AND G(N-7) establishes the important intermediates at neutral to acidic pH. Rate constants for transfer of the G(N-1) proton to H2O, OH-, phosphate, acetate, chloracetate, lactate, and cytosine (N-3) were obtained from 1H nuclear magnetic resonance line width measurements at 360 MHz and were used to estimate the pK or acidity of the exchange site in both the protonated and unprotonated nucleobase. These estimates reveal an increase in acidity of the G(N-1) site corresponding to 2 to 3 pK units as the G(N-7) site is protonated: At neutral pH the G(N-1) site of the protonated purine would be ionized (pK = 6.3). Determinations of phosphate, imidazole, and methylimidazole rate constants for transfer of the amino protons of cCMP provide a more approximate estimate of pK = 7 to 9 for the amino of the protonated pyrimidine. A comparison of the intrinsic amino acidity in the neutral and protonated cytosine is vitiated by the observation that OH- catalyzed exchange in the neutral base is not diffusion limited. This leads to the conclusion that protonation of the nucleobase effects a qualitative increase in the ability of the amino protons to form hydrogen bonds: from very poor in the neutral base to \"normal\" in the conjugate acid.", "contents": "Exchange mechanisms for hydrogen bonding protons of cytidylic and guanylic acids. The pH dependence of buffer catalysis of exchange of the C-4 amino protons of cyclic cytosine 2',3'-monophosphate (cCMP) and the N-1 proton of cyclic guanosine 2',3'-monophosphate (cGMP) conforms to an exchange mechanism, in which protonation of the nucleobases at C(N-3) AND G(N-7) establishes the important intermediates at neutral to acidic pH. Rate constants for transfer of the G(N-1) proton to H2O, OH-, phosphate, acetate, chloracetate, lactate, and cytosine (N-3) were obtained from 1H nuclear magnetic resonance line width measurements at 360 MHz and were used to estimate the pK or acidity of the exchange site in both the protonated and unprotonated nucleobase. These estimates reveal an increase in acidity of the G(N-1) site corresponding to 2 to 3 pK units as the G(N-7) site is protonated: At neutral pH the G(N-1) site of the protonated purine would be ionized (pK = 6.3). Determinations of phosphate, imidazole, and methylimidazole rate constants for transfer of the amino protons of cCMP provide a more approximate estimate of pK = 7 to 9 for the amino of the protonated pyrimidine. A comparison of the intrinsic amino acidity in the neutral and protonated cytosine is vitiated by the observation that OH- catalyzed exchange in the neutral base is not diffusion limited. This leads to the conclusion that protonation of the nucleobase effects a qualitative increase in the ability of the amino protons to form hydrogen bonds: from very poor in the neutral base to \"normal\" in the conjugate acid."}
{"id": "PMID:29661", "title": "Refolding transition of alpha-chymotrypsin: pH and salt dependence.", "content": "It is well known that alpha-chymotrypsin can exist in two major conformational states, only one of which is active. We have examined the pH (pH 2.0--11.0) and salt (ionic strength 0.01--1.0) dependence of the transition between the active and inactive forms in detail. At low pH (pH 2.0--6.0) the equilibrium is very dependent on salt concentration, with high salt concentrations effectively stabilizing the active conformation. This apparent stabilization is an artifact due to the salt-dependent dimerization of alpha-chymotrypsin, and our data show that only active species form dimers and higher aggregates. At neutral pH (6.0--8.0) dimerization is absent, yet an ionic strength dependence remains. The effects show no lyotropic order and appear to be due to preferential salt binding to the active conformation at one or possibly a few sites. Above pH 6 (pH 6.0--11.0), the pH dependence can be described by a two-ionization mechanism at all ionic strengths. We report values for all seven equilibrium constants in the proposed mechanism at four ionic strengths (mu = 0.01, 0.05, 0.2, and 1.0). The transition is the first \"refolding\" transition to be studied at high precision, but, even so, certain decisions about the mechanism must await higher experimental precision not available with present methods.", "contents": "Refolding transition of alpha-chymotrypsin: pH and salt dependence. It is well known that alpha-chymotrypsin can exist in two major conformational states, only one of which is active. We have examined the pH (pH 2.0--11.0) and salt (ionic strength 0.01--1.0) dependence of the transition between the active and inactive forms in detail. At low pH (pH 2.0--6.0) the equilibrium is very dependent on salt concentration, with high salt concentrations effectively stabilizing the active conformation. This apparent stabilization is an artifact due to the salt-dependent dimerization of alpha-chymotrypsin, and our data show that only active species form dimers and higher aggregates. At neutral pH (6.0--8.0) dimerization is absent, yet an ionic strength dependence remains. The effects show no lyotropic order and appear to be due to preferential salt binding to the active conformation at one or possibly a few sites. Above pH 6 (pH 6.0--11.0), the pH dependence can be described by a two-ionization mechanism at all ionic strengths. We report values for all seven equilibrium constants in the proposed mechanism at four ionic strengths (mu = 0.01, 0.05, 0.2, and 1.0). The transition is the first \"refolding\" transition to be studied at high precision, but, even so, certain decisions about the mechanism must await higher experimental precision not available with present methods."}
{"id": "PMID:29662", "title": "Chloride ion binding to human plasma albumin from chlorine-35 quadrupole relaxation.", "content": "The 35Cl nuclear magnetic quadrupole relaxation enhancement on binding of chloride ions to human plasma albumin (HPA) has been studied under conditions of variable temperature, pH, ionic strength, protein, and sodium dodecyl sulfate concentration. A small number (less than 10) of chloride ions, most of which are bound to the primary detergent binding sites, contribute a major portion of the relaxation enhancement (greater than 80% at neutral pH). A comparison of the pH dependence of the relaxation rate with the hydrogen ion titration curve, which was determined and analyzed, identified ten lysyl and arginyl residues as being involved in the chloride ion binding. These data, in conjuction with NaDodSO4 titrations at different pH values and the amino acid sequence of HPA, suggests that the high-affinity chloride-binding sites are doubly cationic at neutral pH. An irreversible dimerization at acidic pH and 5 x 10(-5) m HPA was detected. The data also indicate the presence of internal modes of motion in the expanded forms of the HPA molecule, probably an independent reorientation of domains. The rate of exchange of chloride ions was shown to be much higher than the corresponding intrinsic relaxation rate in the temperature range 2--26 degrees C and pH values ranging from 4.0 to 10.5. No indications of protein-protein interaction could be found up to the physiological concentration of ca. 6 x 10(-4)m HPA at either neutral or alkaline pH. The mechanistic basis for HPA's exceptional capacity for binding of inorganic anions was discussed.", "contents": "Chloride ion binding to human plasma albumin from chlorine-35 quadrupole relaxation. The 35Cl nuclear magnetic quadrupole relaxation enhancement on binding of chloride ions to human plasma albumin (HPA) has been studied under conditions of variable temperature, pH, ionic strength, protein, and sodium dodecyl sulfate concentration. A small number (less than 10) of chloride ions, most of which are bound to the primary detergent binding sites, contribute a major portion of the relaxation enhancement (greater than 80% at neutral pH). A comparison of the pH dependence of the relaxation rate with the hydrogen ion titration curve, which was determined and analyzed, identified ten lysyl and arginyl residues as being involved in the chloride ion binding. These data, in conjuction with NaDodSO4 titrations at different pH values and the amino acid sequence of HPA, suggests that the high-affinity chloride-binding sites are doubly cationic at neutral pH. An irreversible dimerization at acidic pH and 5 x 10(-5) m HPA was detected. The data also indicate the presence of internal modes of motion in the expanded forms of the HPA molecule, probably an independent reorientation of domains. The rate of exchange of chloride ions was shown to be much higher than the corresponding intrinsic relaxation rate in the temperature range 2--26 degrees C and pH values ranging from 4.0 to 10.5. No indications of protein-protein interaction could be found up to the physiological concentration of ca. 6 x 10(-4)m HPA at either neutral or alkaline pH. The mechanistic basis for HPA's exceptional capacity for binding of inorganic anions was discussed."}
{"id": "PMID:29663", "title": "Estimation of transmembrane pH gradients from phase equilibria of spin-labeled amines.", "content": "Spin-labeled secondary amines have been used to measure transmembrane proton gradients in sonicated liposomes. The electron paramagnetic resonance spectra of these probes show changes in the ratio of membrane associated to free aqueous probe as a function of transmembrane pH gradient. As the pH gradient is increased, inside acidic, the amount of membrane associated probe increases. The results are accounted for by a simple thermodynamic theory.", "contents": "Estimation of transmembrane pH gradients from phase equilibria of spin-labeled amines. Spin-labeled secondary amines have been used to measure transmembrane proton gradients in sonicated liposomes. The electron paramagnetic resonance spectra of these probes show changes in the ratio of membrane associated to free aqueous probe as a function of transmembrane pH gradient. As the pH gradient is increased, inside acidic, the amount of membrane associated probe increases. The results are accounted for by a simple thermodynamic theory."}
{"id": "PMID:29664", "title": "Cytochromes and gastric acid secretion. A reevaluation of mucosal acidification experiments.", "content": "Using an improved spectrophotometer, we have reinvestigated the report (Hersey, S.J. (1974) Biochim. Biophys. Acta 344, 157--203) that acidification of the mucosal surface of frog gastric mucosa produces a crossover point between flavoprotein and cytochrome b, thus identifying a site of energy coupling between the cytochrome and H+ transport systems. While we find spectrophotometric changes upon addition of HCl to the mucosal solution, we find similar changes upon addition of NaCl without pH change, but no changes when the pH is lowered by substitution of H+ for Na+ at constant osmolality. We show that osmolality changes, with consequent alteration in tissue light scattering, are responsible for these effects. Further, we can show that the pH changes used do not inhibit acid secretion, and that one cannot do so without osmolality increase. We conclude that the imputed crossover point is not demonstrated, and that models based on its existence must be revised.", "contents": "Cytochromes and gastric acid secretion. A reevaluation of mucosal acidification experiments. Using an improved spectrophotometer, we have reinvestigated the report (Hersey, S.J. (1974) Biochim. Biophys. Acta 344, 157--203) that acidification of the mucosal surface of frog gastric mucosa produces a crossover point between flavoprotein and cytochrome b, thus identifying a site of energy coupling between the cytochrome and H+ transport systems. While we find spectrophotometric changes upon addition of HCl to the mucosal solution, we find similar changes upon addition of NaCl without pH change, but no changes when the pH is lowered by substitution of H+ for Na+ at constant osmolality. We show that osmolality changes, with consequent alteration in tissue light scattering, are responsible for these effects. Further, we can show that the pH changes used do not inhibit acid secretion, and that one cannot do so without osmolality increase. We conclude that the imputed crossover point is not demonstrated, and that models based on its existence must be revised."}
{"id": "PMID:29665", "title": "Comparative studies on the effects of pH and Ca2+ on bilayers of various negatively charged phospholipids and their mixtures with phosphatidylcholine.", "content": "(1) The thermotropic behaviour of dimyristoyl phosphatidylglycerol, phosphatidylserine, phosphatidic acid and phosphatidylcholine was investigated by differential scanning calorimetry and freeze-fracture electron microscopy as a function of pH and of Ca2+ concentration. (2) From the thermotropic behaviour as a function of pH, profiles could be constructed from which apparent pK values of the charged groups of the lipids could be determined. (3) Excess Ca2+ induced a shift of the total phase transition in 14 : 0/14 : 0-glycerophosphocholine and 14 : 0/14 : 0-glycerophosphoglycerol mixtures. In 14 : 0/14 : 0-glycerophosphocholine bilayers containing 16 : 0/16 : 0-glycerophosphoglycerol lateral phase separation was induced by Ca2+. (4) Up to molar ratios of 1 : 2 of 14 : 0/14 : 0-glycerophosphoserine to 14 : 0/14: 0-glycerophosphocholine, excess Ca2+ induced lateral phase separation. Addition to mixtures of higher molar ratios caused segregation into different structures: the liposome organization and the stacked lamellae/cylindrical organization. (5) Addition of excess Ca2+ to mixtures of 14 : 0/14 : 0-glycerophosphocholine and 14 : 0/14 : 0-phosphatidic acid caused, independent of the molar ratio, separation into two structural different organizations. (6) The nature of Ca2+-induced changes in bilayers containing negatively charged phospholipids is strongly dependent on the character of the polar headgroup of the negatively charged phospholipid involved.", "contents": "Comparative studies on the effects of pH and Ca2+ on bilayers of various negatively charged phospholipids and their mixtures with phosphatidylcholine. (1) The thermotropic behaviour of dimyristoyl phosphatidylglycerol, phosphatidylserine, phosphatidic acid and phosphatidylcholine was investigated by differential scanning calorimetry and freeze-fracture electron microscopy as a function of pH and of Ca2+ concentration. (2) From the thermotropic behaviour as a function of pH, profiles could be constructed from which apparent pK values of the charged groups of the lipids could be determined. (3) Excess Ca2+ induced a shift of the total phase transition in 14 : 0/14 : 0-glycerophosphocholine and 14 : 0/14 : 0-glycerophosphoglycerol mixtures. In 14 : 0/14 : 0-glycerophosphocholine bilayers containing 16 : 0/16 : 0-glycerophosphoglycerol lateral phase separation was induced by Ca2+. (4) Up to molar ratios of 1 : 2 of 14 : 0/14 : 0-glycerophosphoserine to 14 : 0/14: 0-glycerophosphocholine, excess Ca2+ induced lateral phase separation. Addition to mixtures of higher molar ratios caused segregation into different structures: the liposome organization and the stacked lamellae/cylindrical organization. (5) Addition of excess Ca2+ to mixtures of 14 : 0/14 : 0-glycerophosphocholine and 14 : 0/14 : 0-phosphatidic acid caused, independent of the molar ratio, separation into two structural different organizations. (6) The nature of Ca2+-induced changes in bilayers containing negatively charged phospholipids is strongly dependent on the character of the polar headgroup of the negatively charged phospholipid involved."}
{"id": "PMID:29667", "title": "The hydrolysis of triacylglycerol and diacylglycerol by a rat brain microsomal lipase with an acidic pH optimum.", "content": "Lipase activity towards triacylglycerol and diacylglycerol was measured at pH 4.8 using a microsomal preparation from rat brain as the enzyme source. The optimal pH for the hydrolysis of triacylglycerol was 4.8, with only minor lipolytic activity in the alkaline pH range. Diacylglycerol was the major product of triacylglycerol hydrolysis, with only little monoacylglycerol being formed. When diacylglycerol was the starting substrate it was hydrolyzed at a rate 10-fold greater than triacylglycerol, and the product was monoacylglycerol. The enzyme showed positional specificity for the fatty acid moieties located at the primary positions of sn-glycerol. 1,3-Diacylglycerol was hydrolyzed at greater than twice the rate of the corresponding 1,2(2,3)-isomer.", "contents": "The hydrolysis of triacylglycerol and diacylglycerol by a rat brain microsomal lipase with an acidic pH optimum. Lipase activity towards triacylglycerol and diacylglycerol was measured at pH 4.8 using a microsomal preparation from rat brain as the enzyme source. The optimal pH for the hydrolysis of triacylglycerol was 4.8, with only minor lipolytic activity in the alkaline pH range. Diacylglycerol was the major product of triacylglycerol hydrolysis, with only little monoacylglycerol being formed. When diacylglycerol was the starting substrate it was hydrolyzed at a rate 10-fold greater than triacylglycerol, and the product was monoacylglycerol. The enzyme showed positional specificity for the fatty acid moieties located at the primary positions of sn-glycerol. 1,3-Diacylglycerol was hydrolyzed at greater than twice the rate of the corresponding 1,2(2,3)-isomer."}
{"id": "PMID:29669", "title": "Kinetics and mechanism of dissociation of zinc ion from carbonic anhydrase.", "content": "The kinetics of dissociation of Zn2+ from the metalloenzyme carbonic anhydrase was measured over a range of pH, temperature, and acetate concentration. The rate of dissociation is extremely slow at neutral pH (t1/2 approximately 3) years, 4 degrees C), but increases in almost direct proportion to the hydrogen ion concentration and is enhanced in the presence of 1,10-phenanthroline or acetate. The thermodynamic stability of the zinc-apoenzyme complex was determined over a range of pH from rate data on binding and dissociation (stability constants 10(9)-10(11) M-1, 25 degrees C). The great stability of the complex and slow exchange of the apoenzyme ligand is attributed, at least in part, to the rigidity of the multidentate protein ligand.", "contents": "Kinetics and mechanism of dissociation of zinc ion from carbonic anhydrase. The kinetics of dissociation of Zn2+ from the metalloenzyme carbonic anhydrase was measured over a range of pH, temperature, and acetate concentration. The rate of dissociation is extremely slow at neutral pH (t1/2 approximately 3) years, 4 degrees C), but increases in almost direct proportion to the hydrogen ion concentration and is enhanced in the presence of 1,10-phenanthroline or acetate. The thermodynamic stability of the zinc-apoenzyme complex was determined over a range of pH from rate data on binding and dissociation (stability constants 10(9)-10(11) M-1, 25 degrees C). The great stability of the complex and slow exchange of the apoenzyme ligand is attributed, at least in part, to the rigidity of the multidentate protein ligand."}
{"id": "PMID:29672", "title": "[Stimulation mechanism of soluble ATPase from chloroplasts (CF1)].", "content": "Effects of various compounds on Mg-dependent ATPase activity of chloroplast coupling factor--CF1--were studied. It was shown that the stimulating effect of compounds is increased with the increase in their hydrophobicity. Under given experimental conditions all compounds under study readily accept and donate protons. The maximal efficiency is reached when pH of the medium is close to the pK value of conjugated acid. It is assumed that the stimulating effects of compounds on Mg-dependent chloroplast ATPase consist in the increase of the rate of the limiting step of enzyme induced proton translocation coupled to the catalytic step of ATP hydrolysis.", "contents": "[Stimulation mechanism of soluble ATPase from chloroplasts (CF1)]. Effects of various compounds on Mg-dependent ATPase activity of chloroplast coupling factor--CF1--were studied. It was shown that the stimulating effect of compounds is increased with the increase in their hydrophobicity. Under given experimental conditions all compounds under study readily accept and donate protons. The maximal efficiency is reached when pH of the medium is close to the pK value of conjugated acid. It is assumed that the stimulating effects of compounds on Mg-dependent chloroplast ATPase consist in the increase of the rate of the limiting step of enzyme induced proton translocation coupled to the catalytic step of ATP hydrolysis."}
{"id": "PMID:29673", "title": "[Isolation and properties of bovine kidney aminopeptidase A].", "content": "Aminopeptidase A, which specifically hydrolyses N-terminal dicarbonic amino acid residues containing free alpha-amino groups, is isolated from bovine kidney. The enzyme is 500-fold purified and is homogenous under electrophoresis and ultracentrifugation. Aminopeptidase A has pH optimum of 7.5, it is activated with Ca2+ and inactivated with EDTA. Its molecular weight is 53000. The enzyme hydrolyses alpha-L-aspartyl-beta-naphtylamide and splits peptides having N-terminal glycine, lysine, arginine and alanine are hydrolyzed by the enzyme much slower. Aminopeptidase A does not attack alpha-L-alanyl-beta-naphtylamide, leucineamide, insulin, peptides with blocked N-terminal amino acid and peptides which have proline to be the second N-terminal amino acid.", "contents": "[Isolation and properties of bovine kidney aminopeptidase A]. Aminopeptidase A, which specifically hydrolyses N-terminal dicarbonic amino acid residues containing free alpha-amino groups, is isolated from bovine kidney. The enzyme is 500-fold purified and is homogenous under electrophoresis and ultracentrifugation. Aminopeptidase A has pH optimum of 7.5, it is activated with Ca2+ and inactivated with EDTA. Its molecular weight is 53000. The enzyme hydrolyses alpha-L-aspartyl-beta-naphtylamide and splits peptides having N-terminal glycine, lysine, arginine and alanine are hydrolyzed by the enzyme much slower. Aminopeptidase A does not attack alpha-L-alanyl-beta-naphtylamide, leucineamide, insulin, peptides with blocked N-terminal amino acid and peptides which have proline to be the second N-terminal amino acid."}
{"id": "PMID:29668", "title": "[Effect of adsorption on the structure and properties of hemoglobin].", "content": "Adsorption spectra of Hb+ and HbO2 adsorbed on silica and monolayers cholesterol supported on silica have been studied. It is shown that immobilization leads to new states of proteins, their properties depending on the nature of support and conditions of adsorption. Adsorption of haemoglobin leads to its inactivation. The rate of inactivation decreases with an increase of surface concentration of haemoglobin and with simultaneous adsorption of inert proteins.", "contents": "[Effect of adsorption on the structure and properties of hemoglobin]. Adsorption spectra of Hb+ and HbO2 adsorbed on silica and monolayers cholesterol supported on silica have been studied. It is shown that immobilization leads to new states of proteins, their properties depending on the nature of support and conditions of adsorption. Adsorption of haemoglobin leads to its inactivation. The rate of inactivation decreases with an increase of surface concentration of haemoglobin and with simultaneous adsorption of inert proteins."}
{"id": "PMID:29674", "title": "[Chemical modification of epsilon-amino lysine groups in horseradish peroxidase. Its effect on catalytic properties and spatial structure of the enzyme].", "content": "Effect of chemical modification of horseradish peroxidase lysine epsilon-amino groups by propionic, butyric, valeric, succinic anhydrides and trinitrobenzolsulfonic acid (TNBS) on catalytic properties of the enzyme is investigated. All the preparations of modified peroxidase have 100% peroxidase activity for o-dianizidine at pH 7.0, which indicates the absence of lysine epsilon-amino group in the enzyme active site. pH-dependencies of modified peroxidase relative activity are studied; modification by anhydrides of monobasic acids is not found to result in changes of the relative activity pH-profile, while modification by succinic anhydride widens it. Absorption and circular dichoism spectra of native and modified peroxidase within 260--270 nm are obtained, some changes in the enzyme tertiary structure after its epsilon-amino groups modification are observed. Modification of four epsilon-amino groups by buturic and succinic anhydrides and of three epsilon-amino groups by TNBS is found to increase the regidity of protein surrounding of heme, and modification of six epsilon-amino groups by TNBS results in more unwrapped enzyme structure as compared with its native molecule.", "contents": "[Chemical modification of epsilon-amino lysine groups in horseradish peroxidase. Its effect on catalytic properties and spatial structure of the enzyme]. Effect of chemical modification of horseradish peroxidase lysine epsilon-amino groups by propionic, butyric, valeric, succinic anhydrides and trinitrobenzolsulfonic acid (TNBS) on catalytic properties of the enzyme is investigated. All the preparations of modified peroxidase have 100% peroxidase activity for o-dianizidine at pH 7.0, which indicates the absence of lysine epsilon-amino group in the enzyme active site. pH-dependencies of modified peroxidase relative activity are studied; modification by anhydrides of monobasic acids is not found to result in changes of the relative activity pH-profile, while modification by succinic anhydride widens it. Absorption and circular dichoism spectra of native and modified peroxidase within 260--270 nm are obtained, some changes in the enzyme tertiary structure after its epsilon-amino groups modification are observed. Modification of four epsilon-amino groups by buturic and succinic anhydrides and of three epsilon-amino groups by TNBS is found to increase the regidity of protein surrounding of heme, and modification of six epsilon-amino groups by TNBS results in more unwrapped enzyme structure as compared with its native molecule."}
{"id": "PMID:29675", "title": "[Immobilization of glyceraldehyde-3-phosphate dehydrogenase by non-covalent binding to specific antibodies and Fab-fragments coupled to Sepharose].", "content": "Rabbit antibodies to rat skeletal muscle glyceraldehyde-3-phosphate dehydrogenase, as well as monovalent Fab fragments of these antibodies were coupled to CNBr-activated Sepharose 4B. Rat skeletal muscle glyceraldehyde-3-phosphate dehydrogenase was then immobilized on a matrix by non-covalent binding to specific antibodies. Immobilized enzyme retains approximately 90% catalytic activity of the soluble dehydrogenase; pH optimum of activity and the Km value observed are changed as compared to the enzyme in solution. Glyceraldehyde-3-phosphate dehydrogenase immobilized on specific antibodies is shown to undergo adenine nucleotide-induced dissociation into dimers. The immobilized dimeric form of the enzyme thus obtained is catalytically active and capable of reassociating with the dimers of apoglyceraldehyde-3-phosphate dehydrogenase added in solution to the suspension of Sepharose.", "contents": "[Immobilization of glyceraldehyde-3-phosphate dehydrogenase by non-covalent binding to specific antibodies and Fab-fragments coupled to Sepharose]. Rabbit antibodies to rat skeletal muscle glyceraldehyde-3-phosphate dehydrogenase, as well as monovalent Fab fragments of these antibodies were coupled to CNBr-activated Sepharose 4B. Rat skeletal muscle glyceraldehyde-3-phosphate dehydrogenase was then immobilized on a matrix by non-covalent binding to specific antibodies. Immobilized enzyme retains approximately 90% catalytic activity of the soluble dehydrogenase; pH optimum of activity and the Km value observed are changed as compared to the enzyme in solution. Glyceraldehyde-3-phosphate dehydrogenase immobilized on specific antibodies is shown to undergo adenine nucleotide-induced dissociation into dimers. The immobilized dimeric form of the enzyme thus obtained is catalytically active and capable of reassociating with the dimers of apoglyceraldehyde-3-phosphate dehydrogenase added in solution to the suspension of Sepharose."}
{"id": "PMID:29676", "title": "[Glucose-isomerizing enzyme from Actinomyces olivocinereus and its immobilization on aminosilochrome].", "content": "Glucose-isomerizing enzyme was isolated from the culture of Actinomyces olivocinereus. It was purified by the chromatography on DEAE-cellulose. The samples of glucose-isomerasing enzyme are homogeneous according to the results of analytical electrophoresis and ultracentrifugation. Glucose-isomerase is more stable than soluble one. The pH-optima of soluble and immobilized enzymes are 8.5 and 7.5, respectively. The temperature optimum of immobilized enzyme, Km, V, and activation energy do not change during immobilization. The immobilized sample has 58% activity of soluble enzyme.", "contents": "[Glucose-isomerizing enzyme from Actinomyces olivocinereus and its immobilization on aminosilochrome]. Glucose-isomerizing enzyme was isolated from the culture of Actinomyces olivocinereus. It was purified by the chromatography on DEAE-cellulose. The samples of glucose-isomerasing enzyme are homogeneous according to the results of analytical electrophoresis and ultracentrifugation. Glucose-isomerase is more stable than soluble one. The pH-optima of soluble and immobilized enzymes are 8.5 and 7.5, respectively. The temperature optimum of immobilized enzyme, Km, V, and activation energy do not change during immobilization. The immobilized sample has 58% activity of soluble enzyme."}
{"id": "PMID:29677", "title": "[Changes in the conformation of myo-inositol residues in triphosphoinositides].", "content": "Dependency of optical rotation of di- and triphosphoinositide water solutions on pH is investigated. The inversion of myo-inosite ring in triphosphoinositide molecule is found to take place at pH range corresponding to the transition of phosphomonoesters from monoanionic into dianionic form. Stabilization of optical rotation is observed at pH range, where one monoester phosphate group is in monoanionic form and the other--in dianionic form. Probably, triphosphoinositide is in the conformation (distorted boat) at this pH range. Diphosphoinositide does not change its optical rotation under pH changes of water or organic solutions. A contribution is estimated of free conformational energy into standard free energy of splitting triphosphoinositide phosphate group depending on pH value. It is concluded that low energy phosphate bond becomes high energy bond due to the free electrostatic interaction of dianionic phosphate group with other negatively charged group in sin-clynal conformation.", "contents": "[Changes in the conformation of myo-inositol residues in triphosphoinositides]. Dependency of optical rotation of di- and triphosphoinositide water solutions on pH is investigated. The inversion of myo-inosite ring in triphosphoinositide molecule is found to take place at pH range corresponding to the transition of phosphomonoesters from monoanionic into dianionic form. Stabilization of optical rotation is observed at pH range, where one monoester phosphate group is in monoanionic form and the other--in dianionic form. Probably, triphosphoinositide is in the conformation (distorted boat) at this pH range. Diphosphoinositide does not change its optical rotation under pH changes of water or organic solutions. A contribution is estimated of free conformational energy into standard free energy of splitting triphosphoinositide phosphate group depending on pH value. It is concluded that low energy phosphate bond becomes high energy bond due to the free electrostatic interaction of dianionic phosphate group with other negatively charged group in sin-clynal conformation."}
{"id": "PMID:29678", "title": "Effect of hypoxia on monoamine synthesis in brains of developing rats. III. Various O2 levels.", "content": "1-, 4-, 14- and 28-day-old rats were exposed to a hypoxic environment of 5.9, 8.0 or 12.0% O2 during a period of 30 min. In the brain, tyrosine hydroxylase and tryptophan hydroxylase activity was studied in vivo by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. Tyrosine and tryptophan levels in the brain were measured simultaneously. The brain tyrosine and tryptophan levels were generally not influenced either by age or hypoxic levels. Tyrosine and tryptophan hydroxylase activity decreased to about the same extent during the various hypoxic levels at all ages studied. It is concluded that the first, rate-limiting, step in the synthesis of the monoamine neurotransmittors dopamine (DA), noradrenaline (NA) and 5-hydroxy-tryptophan (5-HT) is affected during moderate as well as severe hypoxia at all stages of development.", "contents": "Effect of hypoxia on monoamine synthesis in brains of developing rats. III. Various O2 levels. 1-, 4-, 14- and 28-day-old rats were exposed to a hypoxic environment of 5.9, 8.0 or 12.0% O2 during a period of 30 min. In the brain, tyrosine hydroxylase and tryptophan hydroxylase activity was studied in vivo by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. Tyrosine and tryptophan levels in the brain were measured simultaneously. The brain tyrosine and tryptophan levels were generally not influenced either by age or hypoxic levels. Tyrosine and tryptophan hydroxylase activity decreased to about the same extent during the various hypoxic levels at all ages studied. It is concluded that the first, rate-limiting, step in the synthesis of the monoamine neurotransmittors dopamine (DA), noradrenaline (NA) and 5-hydroxy-tryptophan (5-HT) is affected during moderate as well as severe hypoxia at all stages of development."}
{"id": "PMID:29679", "title": "[Mechanisms of changes in the mass of the organs central to immunity during adenovirus carcinogenesis].", "content": "The spleen cells transfer from mice CBA at the 25th day of the carcinogenesis latent period induced by adenovirus SA7(S8) to newborn syngeneic animals caused the graft versus host reaction in them. There was splenomegaly and progressive decrease in weight of the recipients' thymus. Analogous alterations of lymphoid organs were noted in the animals infected during the neonatal period by oncogenic adenovirus SA7(C8). Results showed that adenoviral carcinogenesis had some manifestations of autoimmune disease.", "contents": "[Mechanisms of changes in the mass of the organs central to immunity during adenovirus carcinogenesis]. The spleen cells transfer from mice CBA at the 25th day of the carcinogenesis latent period induced by adenovirus SA7(S8) to newborn syngeneic animals caused the graft versus host reaction in them. There was splenomegaly and progressive decrease in weight of the recipients' thymus. Analogous alterations of lymphoid organs were noted in the animals infected during the neonatal period by oncogenic adenovirus SA7(C8). Results showed that adenoviral carcinogenesis had some manifestations of autoimmune disease."}
{"id": "PMID:29684", "title": "Characterization of adrenoceptors mediating positive inotropic responses in the ventricular myocardium of the dog.", "content": "1 The pharmacological characteristics of adrenoceptors mediating the positive inotropic action in the dog heart were assessed by the use of blood-perfused papillary muscles and isolated strips of ventricular myocardium.2 On the blood-perfused papillary muscle driven at 2 Hz and in sinus node preparations, phenylephrine induced positive inotropic and chronotropic responses in the same dose range and was much less potent than isoprenaline. The dose-response curve for the chronotropic action of phenylephrine was parallel to that of isoprenaline, whilst the dose-response curve for the inotropic action of phenylephrine was less steep than that of isoprenaline.3 The infusion of pindolol, a beta-adrenoceptor blocking agent, at a rate of 1 mug/min, shifted the isoprenaline dose-response curves to the right, and to the same extent, in both papillary muscle and sinus node preparations. In contrast to isoprenaline, the antagonism of phenylephrine by pindolol was noncompetitive. Phentolamine did not affect the positive inotropic and chronotropic actions of phenylephrine.4 On isolated ventricular strips alpha-adrenoceptor blockade by 10(-6) M phentolamine did not affect dose-response curves to phenylephrine or dopamine. Pindolol shifted the dopamine dose-response curves to the right in a competitive manner and those of phenylephrine in a noncompetitive manner.5 On ventricular strips from reserpine-pretreated dogs phenylephrine and tyramine dose-response curves were shifted markedly to the right and downwards. Desipramine (10(-5) M) which enhanced the action of noradrenaline considerably reduced the myocardial responses of phenylephrine.6 Papaverine (10(-5) M) decreased the threshold concentration of phenylephrine required to stimulate the myocardium and shifted phenylephrine dose-response curves to the left.7 Raising the temperature from 32 degrees C to 37 degrees C shifted phenylephrine dose-response curves to the right; when the temperature was raised from 37 degrees C to 42 degrees C the affinity of the drug was not changed.8 Other alpha-adrenoceptor stimulants, methoxamine and clonidine, decreased the active tension of ventricular strips. The responses to noradrenaline and adrenaline (in the presence of pindolol; 3 x 10(-8) M) were not affected by phentolamine (10(-6) M).9 The results indicate that adrenoceptors mediating positive inotropic responses in the dog ventricle are of the beta-type and that post-synaptic alpha-adrenoceptors are not involved. Phenylephrine acts mainly by releasing noradrenaline from adrenergic nerve endings and partly by a weak direct action on beta-adrenoceptors.", "contents": "Characterization of adrenoceptors mediating positive inotropic responses in the ventricular myocardium of the dog. 1 The pharmacological characteristics of adrenoceptors mediating the positive inotropic action in the dog heart were assessed by the use of blood-perfused papillary muscles and isolated strips of ventricular myocardium.2 On the blood-perfused papillary muscle driven at 2 Hz and in sinus node preparations, phenylephrine induced positive inotropic and chronotropic responses in the same dose range and was much less potent than isoprenaline. The dose-response curve for the chronotropic action of phenylephrine was parallel to that of isoprenaline, whilst the dose-response curve for the inotropic action of phenylephrine was less steep than that of isoprenaline.3 The infusion of pindolol, a beta-adrenoceptor blocking agent, at a rate of 1 mug/min, shifted the isoprenaline dose-response curves to the right, and to the same extent, in both papillary muscle and sinus node preparations. In contrast to isoprenaline, the antagonism of phenylephrine by pindolol was noncompetitive. Phentolamine did not affect the positive inotropic and chronotropic actions of phenylephrine.4 On isolated ventricular strips alpha-adrenoceptor blockade by 10(-6) M phentolamine did not affect dose-response curves to phenylephrine or dopamine. Pindolol shifted the dopamine dose-response curves to the right in a competitive manner and those of phenylephrine in a noncompetitive manner.5 On ventricular strips from reserpine-pretreated dogs phenylephrine and tyramine dose-response curves were shifted markedly to the right and downwards. Desipramine (10(-5) M) which enhanced the action of noradrenaline considerably reduced the myocardial responses of phenylephrine.6 Papaverine (10(-5) M) decreased the threshold concentration of phenylephrine required to stimulate the myocardium and shifted phenylephrine dose-response curves to the left.7 Raising the temperature from 32 degrees C to 37 degrees C shifted phenylephrine dose-response curves to the right; when the temperature was raised from 37 degrees C to 42 degrees C the affinity of the drug was not changed.8 Other alpha-adrenoceptor stimulants, methoxamine and clonidine, decreased the active tension of ventricular strips. The responses to noradrenaline and adrenaline (in the presence of pindolol; 3 x 10(-8) M) were not affected by phentolamine (10(-6) M).9 The results indicate that adrenoceptors mediating positive inotropic responses in the dog ventricle are of the beta-type and that post-synaptic alpha-adrenoceptors are not involved. Phenylephrine acts mainly by releasing noradrenaline from adrenergic nerve endings and partly by a weak direct action on beta-adrenoceptors."}
{"id": "PMID:29685", "title": "Sulphasalazine is a potent inhibitor of prostaglandin 15-hydroxydehydrogenase: possible basis for therapeutic action in ulcerative colitis.", "content": "Sulphasalazine is a potent and selective inhibitor in vitro of prostaglandin 15-hydroxydehydrogenase in rabbit colon (ID50 = 50 micrometer) and in several other organs of different species, but does not inhibit prostaglandin delta-13 reductase or microsomal prostaglandin synthesis from arachidonic acid. It is suggested that this action may underly the therapeutic usefulness of sulphasalazine in ulcerative colitis for the prevention of relapse.", "contents": "Sulphasalazine is a potent inhibitor of prostaglandin 15-hydroxydehydrogenase: possible basis for therapeutic action in ulcerative colitis. Sulphasalazine is a potent and selective inhibitor in vitro of prostaglandin 15-hydroxydehydrogenase in rabbit colon (ID50 = 50 micrometer) and in several other organs of different species, but does not inhibit prostaglandin delta-13 reductase or microsomal prostaglandin synthesis from arachidonic acid. It is suggested that this action may underly the therapeutic usefulness of sulphasalazine in ulcerative colitis for the prevention of relapse."}
{"id": "PMID:29686", "title": "Effects of narcotic analgesics on the uptake and release of 5-hydroxytryptamine in rat synaptosomal preparations.", "content": "1 The effects of various narcotic analgesics on the uptake and release of labelled 5-hydroxytryptamine (5-HT) in brain and spinal cord synaptosomes were investigated.2 Methadone was most active in inhibiting 5-HT uptake (IC(50) 2.5 x 10(-7) M). Levorphanol also inhibited 5-HT uptake to a large extent (IC(50) 8.8 x 10(-7) M) while dextrophan, pethidine and pentazocine showed much less activity. Etorphine and morphine had virtually no such activity, with IC(50)S higher than 10(-4) and 10(-3) M respectively.3 The same order of potency as ;5-HT releasers' was found when radioactivity was measured in [(3)H]-5-HT preloaded synaptosomal pellets incubated for 20 min with the various narcotics. Methadone, like chlorimipramine, showed a significant effect at a concentration of 10(-7) M while morphine, at a concentration of 10(-4) M, had no effect.4 When 5-HT release was studied by a perfusion technique, which largely prevents reuptake of the released amine, only fenfluramine, an anorectic agent proposed as a 5-HT releaser, significantly increased spontaneous 5-HT release. These data suggest that the apparent 5-HT release induced by various narcotics in traditional incubation techniques may largely depend on their ability to interfere with neurotransmitter reuptake mechanisms.5 The effects of the various narcotics on 5-HT uptake have no relationship to their relative potency as analgesics in the rat. In the light of their poor effectiveness as 5-HT releasers, it can be concluded that mechanisms other than 5-HT uptake inhibition and release are probably involved in the analgesic effects of these compounds in intact animals.", "contents": "Effects of narcotic analgesics on the uptake and release of 5-hydroxytryptamine in rat synaptosomal preparations. 1 The effects of various narcotic analgesics on the uptake and release of labelled 5-hydroxytryptamine (5-HT) in brain and spinal cord synaptosomes were investigated.2 Methadone was most active in inhibiting 5-HT uptake (IC(50) 2.5 x 10(-7) M). Levorphanol also inhibited 5-HT uptake to a large extent (IC(50) 8.8 x 10(-7) M) while dextrophan, pethidine and pentazocine showed much less activity. Etorphine and morphine had virtually no such activity, with IC(50)S higher than 10(-4) and 10(-3) M respectively.3 The same order of potency as ;5-HT releasers' was found when radioactivity was measured in [(3)H]-5-HT preloaded synaptosomal pellets incubated for 20 min with the various narcotics. Methadone, like chlorimipramine, showed a significant effect at a concentration of 10(-7) M while morphine, at a concentration of 10(-4) M, had no effect.4 When 5-HT release was studied by a perfusion technique, which largely prevents reuptake of the released amine, only fenfluramine, an anorectic agent proposed as a 5-HT releaser, significantly increased spontaneous 5-HT release. These data suggest that the apparent 5-HT release induced by various narcotics in traditional incubation techniques may largely depend on their ability to interfere with neurotransmitter reuptake mechanisms.5 The effects of the various narcotics on 5-HT uptake have no relationship to their relative potency as analgesics in the rat. In the light of their poor effectiveness as 5-HT releasers, it can be concluded that mechanisms other than 5-HT uptake inhibition and release are probably involved in the analgesic effects of these compounds in intact animals."}
{"id": "PMID:29695", "title": "The effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus.", "content": "The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors.", "contents": "The effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus. The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors."}
{"id": "PMID:29697", "title": "SIF cells, cyclic AMP responses, and catecholamines of the guinea pig superior cervical ganglion.", "content": "The superior cervical ganglion (SCG) of the guinea pig has been investigated by a multidisciplinary approach. Dopamine (50 micron) produced no increase in cyclic AMP levels above control values of 27.9 pmole/mg protein, but 50 micron isoproterenol produced cyclic AMP levels of 210 pmole/mg protein, indicating the existence of a beta-adrenergic receptor-adenylate cyclase complex. The SIF cells were studied by fluorescence histochemistry, which indicated that two morphological types were present. A few Type I cells of the guinea pig SCG were solitary, but most were present in clusters containing many Type II cells. Immunohistochemical localization of antibodies to dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) demonstrated that types of SIF cell localize antibodies to DBH but not PNMT, providing strong evidence that norepinephrine is the neurotransmitter for all the SIF cells of the guinea pig SCG. Determination of the ratio of norepinephrine to dopamine confirmed that no other dopamine pools exist in the guinea pig SCG.", "contents": "SIF cells, cyclic AMP responses, and catecholamines of the guinea pig superior cervical ganglion. The superior cervical ganglion (SCG) of the guinea pig has been investigated by a multidisciplinary approach. Dopamine (50 micron) produced no increase in cyclic AMP levels above control values of 27.9 pmole/mg protein, but 50 micron isoproterenol produced cyclic AMP levels of 210 pmole/mg protein, indicating the existence of a beta-adrenergic receptor-adenylate cyclase complex. The SIF cells were studied by fluorescence histochemistry, which indicated that two morphological types were present. A few Type I cells of the guinea pig SCG were solitary, but most were present in clusters containing many Type II cells. Immunohistochemical localization of antibodies to dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) demonstrated that types of SIF cell localize antibodies to DBH but not PNMT, providing strong evidence that norepinephrine is the neurotransmitter for all the SIF cells of the guinea pig SCG. Determination of the ratio of norepinephrine to dopamine confirmed that no other dopamine pools exist in the guinea pig SCG."}
{"id": "PMID:29698", "title": "Amplitude and rate of decay of post-tetanic potentiation are controlled by different mechanisms.", "content": "Evidence is presented that post-tetanic potentiation (PTP) of the cholinergic, fast, Cl- dependent IPSP seen in cell L5 of the abdominal ganglion of Aplysia californica upon eliciting a spoke in cell L10 is due to an increase in spike-evoked transmitter release. The magnitude of the post-tetanic change in spike-evoked release is inversely correlated with the amount of transmitter released by an isolated presynaptic spike. This was found whether the latter was increased by injection of tetraethyl ammonium (TEA) into the soma of L10 or decreased by hyperpolarization of the soma of L10. Neither of these manipulations affected the rate of decay of PTP. The magnitude of PTP was increased and the rate of decay reduced by increasing either the number or frequency of stimuli in the tetanus. Under all conditions PTP decayed with a single exponential time course, asymptotically approaching the unpotentiated magnitude. It is concluded that while both the amplitude and rate of decay of PTP are affected by the frequency and number of stimuli in the tetanus, the underlying mechanism controlling the amplitude of PTP is different from the mechanism controlling the rate of decay of PTP.", "contents": "Amplitude and rate of decay of post-tetanic potentiation are controlled by different mechanisms. Evidence is presented that post-tetanic potentiation (PTP) of the cholinergic, fast, Cl- dependent IPSP seen in cell L5 of the abdominal ganglion of Aplysia californica upon eliciting a spoke in cell L10 is due to an increase in spike-evoked transmitter release. The magnitude of the post-tetanic change in spike-evoked release is inversely correlated with the amount of transmitter released by an isolated presynaptic spike. This was found whether the latter was increased by injection of tetraethyl ammonium (TEA) into the soma of L10 or decreased by hyperpolarization of the soma of L10. Neither of these manipulations affected the rate of decay of PTP. The magnitude of PTP was increased and the rate of decay reduced by increasing either the number or frequency of stimuli in the tetanus. Under all conditions PTP decayed with a single exponential time course, asymptotically approaching the unpotentiated magnitude. It is concluded that while both the amplitude and rate of decay of PTP are affected by the frequency and number of stimuli in the tetanus, the underlying mechanism controlling the amplitude of PTP is different from the mechanism controlling the rate of decay of PTP."}
{"id": "PMID:29702", "title": "Guanyl O6-arylamination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphthylamine.", "content": "The carcinogen N-hydroxy-1-naphthylamine reacted with nucleic acids and protein under slightly acidic conditions (pH 5) to form covalently bound derivatives with 3 to 20 naphthyl residues/1000 monomer units. The level of binding was in the following order: DNA greater than polyguanylic acid greater than denatured DNA and ribosomal RNA greater than serum albumin greater than transfer RNA greater than polyadenylic acid. Reactions with nucleosides and nucleotides were not detected, and the binding of N-hydroxy-1-naphthylamine to DNA was not inhibited by the addition of nucleosides, nucleotides, methionine, or glutathione. The reaction rates were first order with respect to both DNA and N-hydroxy-1-naphthylamine concentrations. Enzymatic hydrolysis of the DNA containing naphthyl residues yielded 3 nucleoside-arylamine adducts. The major adduct was identified by chemical, ultraviolet, nuclear magnetic resonance, and mass spectrometric analyses as N-(deoxyguanosin-O6-yl)-1-naphthylamine. The other two adducts were identified as 2-(deoxyguanosin-O6-yl)-1-naphthylamine and its decomposition product. Direct evidence for acid-dependent arylnitrenium ion formation was obtained by isotope exchange upon solvolysis of N-hydroxy-1-naphthylamine in acidic H2 18O, and carbocation formation was indicated by the formation of the solvolysis products, 1-amino-2-naphthol and 1-amino-4-naphthol. These studies demonstrated the conversion of a carcinogenic N-hydroxy arylamine to electrophilic arylnitrenium ion and carbocation species that display high selectivity toward macromolecules. The roles of these electrophiles and their macromolecular adducts in the initiation of urinary bladder carcinogenesis through formation of promutagenic lesions in DNA are suggested.", "contents": "Guanyl O6-arylamination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphthylamine. The carcinogen N-hydroxy-1-naphthylamine reacted with nucleic acids and protein under slightly acidic conditions (pH 5) to form covalently bound derivatives with 3 to 20 naphthyl residues/1000 monomer units. The level of binding was in the following order: DNA greater than polyguanylic acid greater than denatured DNA and ribosomal RNA greater than serum albumin greater than transfer RNA greater than polyadenylic acid. Reactions with nucleosides and nucleotides were not detected, and the binding of N-hydroxy-1-naphthylamine to DNA was not inhibited by the addition of nucleosides, nucleotides, methionine, or glutathione. The reaction rates were first order with respect to both DNA and N-hydroxy-1-naphthylamine concentrations. Enzymatic hydrolysis of the DNA containing naphthyl residues yielded 3 nucleoside-arylamine adducts. The major adduct was identified by chemical, ultraviolet, nuclear magnetic resonance, and mass spectrometric analyses as N-(deoxyguanosin-O6-yl)-1-naphthylamine. The other two adducts were identified as 2-(deoxyguanosin-O6-yl)-1-naphthylamine and its decomposition product. Direct evidence for acid-dependent arylnitrenium ion formation was obtained by isotope exchange upon solvolysis of N-hydroxy-1-naphthylamine in acidic H2 18O, and carbocation formation was indicated by the formation of the solvolysis products, 1-amino-2-naphthol and 1-amino-4-naphthol. These studies demonstrated the conversion of a carcinogenic N-hydroxy arylamine to electrophilic arylnitrenium ion and carbocation species that display high selectivity toward macromolecules. The roles of these electrophiles and their macromolecular adducts in the initiation of urinary bladder carcinogenesis through formation of promutagenic lesions in DNA are suggested."}
{"id": "PMID:29706", "title": "Estradiol receptor analysis in human breast cancer tissue by isoelectric focusing in polyacrylamide gel.", "content": "Isoelectric focusing in polyacrylamide gel combined with limited proteolysis is a simple and specific method for quantitation of estradiol receptors in breast cancer tissue. At least eight different samples can be analyzed simultaneously on one gel, and the whole procedure, including sample preparation, takes less than 7 hr. In comparison with sucrose gradient centrifugation, isoelectric focusing is more sensitive, possibly due to the short time (1.5 to 2 hr) needed for the analysis. Furthermore, only one incubation with tritium-labeled estradiol is needed for an analysis, which means that a smaller amount of tumor tissue is needed than for most other methods. This fact allows analysis of the estrogen receptor content in tumor material obtained from fine-needle biopsy.", "contents": "Estradiol receptor analysis in human breast cancer tissue by isoelectric focusing in polyacrylamide gel. Isoelectric focusing in polyacrylamide gel combined with limited proteolysis is a simple and specific method for quantitation of estradiol receptors in breast cancer tissue. At least eight different samples can be analyzed simultaneously on one gel, and the whole procedure, including sample preparation, takes less than 7 hr. In comparison with sucrose gradient centrifugation, isoelectric focusing is more sensitive, possibly due to the short time (1.5 to 2 hr) needed for the analysis. Furthermore, only one incubation with tritium-labeled estradiol is needed for an analysis, which means that a smaller amount of tumor tissue is needed than for most other methods. This fact allows analysis of the estrogen receptor content in tumor material obtained from fine-needle biopsy."}
{"id": "PMID:29708", "title": "Calcification of the collagenous axial skeleton of Veretillum cynomorium pall. (Cnidaria: Pennatulacea).", "content": "The axial skeletal rod of Veretillium cynomorium consists of a fibrillar collagenous matrix calcified with calcite. The present paper describes ultrastructural and crystallographic details of its organization and deposition. At the inferior end of the rod is a calcification gradient between the noncalcified tip and the rest of the axis. Initial mineral deposits, which are sometimes associated with cell debris, give rise to calcitic nodules which enlarge by the radical growth of several lobes. These nodules fuse and form the core of the axis. Subsequent increase in diameter of the rod involves the radial development of irregular columns of calcite which arise from the peripheral nodules. Mineral surfaces exhibit a distinctive microarchitecture which can be related to the predominantly c-axis parallel growth of the calcite. Particular attention is paid to the relationship between mineral and matrix. The collagen fibrils, embedded in the calcite but never impregnated with it, are not responsible for the initial nucleation of mineral. The crystallographic orientation of the calcite also appears to be independent of these fibrils.", "contents": "Calcification of the collagenous axial skeleton of Veretillum cynomorium pall. (Cnidaria: Pennatulacea). The axial skeletal rod of Veretillium cynomorium consists of a fibrillar collagenous matrix calcified with calcite. The present paper describes ultrastructural and crystallographic details of its organization and deposition. At the inferior end of the rod is a calcification gradient between the noncalcified tip and the rest of the axis. Initial mineral deposits, which are sometimes associated with cell debris, give rise to calcitic nodules which enlarge by the radical growth of several lobes. These nodules fuse and form the core of the axis. Subsequent increase in diameter of the rod involves the radial development of irregular columns of calcite which arise from the peripheral nodules. Mineral surfaces exhibit a distinctive microarchitecture which can be related to the predominantly c-axis parallel growth of the calcite. Particular attention is paid to the relationship between mineral and matrix. The collagen fibrils, embedded in the calcite but never impregnated with it, are not responsible for the initial nucleation of mineral. The crystallographic orientation of the calcite also appears to be independent of these fibrils."}
{"id": "PMID:29714", "title": "[Effects of levophacetoperane, pemoline, fenozolone, and centrophenoxine on catecholamines and serotonin uptake in various parts of the rat brain].", "content": "These drugs, except centrophenoxine, inhibit in vitro in a competitive manner, norepinephrin uptake in Rat hypothalamus and cortex, and dopamine uptake in corpus striatum and cortex, at higher concentrations than d.l. amphetamine; this alone inhibits serotonin uptake in hypothalamus.", "contents": "[Effects of levophacetoperane, pemoline, fenozolone, and centrophenoxine on catecholamines and serotonin uptake in various parts of the rat brain]. These drugs, except centrophenoxine, inhibit in vitro in a competitive manner, norepinephrin uptake in Rat hypothalamus and cortex, and dopamine uptake in corpus striatum and cortex, at higher concentrations than d.l. amphetamine; this alone inhibits serotonin uptake in hypothalamus."}
{"id": "PMID:29715", "title": "[Induction of hepatic tyrosine transaminase in rats by phenothiazine derivatives and analogs].", "content": "We have showed induction of tyrosine-alpha-ketoglutarate transaminase in hepatic cytosol of Rats (Wistar strain) five hours after intraperitoneal administration of tricyclic compounds (phenothiazine, iminodibenzyl, thioxanthene, thiophenylpyridylamin, dibenzocycloheptadiene, dibenzoxepin derivatives). Chemical structure of these molecules is very important: sulfur atom (phenothiazine, thioxanthene), some substituants like chlorine (chlorpromazine, chlorprothixene) and 2'-dimethylaminopropyl chain (promethazine) increase this inductive effect.", "contents": "[Induction of hepatic tyrosine transaminase in rats by phenothiazine derivatives and analogs]. We have showed induction of tyrosine-alpha-ketoglutarate transaminase in hepatic cytosol of Rats (Wistar strain) five hours after intraperitoneal administration of tricyclic compounds (phenothiazine, iminodibenzyl, thioxanthene, thiophenylpyridylamin, dibenzocycloheptadiene, dibenzoxepin derivatives). Chemical structure of these molecules is very important: sulfur atom (phenothiazine, thioxanthene), some substituants like chlorine (chlorpromazine, chlorprothixene) and 2'-dimethylaminopropyl chain (promethazine) increase this inductive effect."}
{"id": "PMID:29716", "title": "[Mechanism of induction of tyrosine in rat liver by phenothiazine derivatives and related chemical compounds].", "content": "Increase of hepatic tyrosine-alpha-ketoglutarate transaminase is observed in Rats (Wistar strain) after intraperitoneal administration of tricyclic compounds (phenothiazin and related structure derivatives). This is an induction process: actinomycine D inhibits this effect. This action is not mediated by glucocorticoids: induction persists in adrenalectomized Rats. The mechanism of action is different too: additive effects are found after simultaneous injection of glucocorticoid and tricyclic drug.", "contents": "[Mechanism of induction of tyrosine in rat liver by phenothiazine derivatives and related chemical compounds]. Increase of hepatic tyrosine-alpha-ketoglutarate transaminase is observed in Rats (Wistar strain) after intraperitoneal administration of tricyclic compounds (phenothiazin and related structure derivatives). This is an induction process: actinomycine D inhibits this effect. This action is not mediated by glucocorticoids: induction persists in adrenalectomized Rats. The mechanism of action is different too: additive effects are found after simultaneous injection of glucocorticoid and tricyclic drug."}
{"id": "PMID:29720", "title": "Kinetics of the reactions of unconjugated and conjugated bilirubins with p-diazobenzenesulfonic acid.", "content": "We report the kinetics of the reactions of unconjugated bilirubin and conjugated bilirubin with p-diazobenzene sulfonic acid in aqueous media. Our studies confirm that each reaction proceeds in two steps and that the second step is catalyzed by sulfanilic acid. In the presence of an excess of p-diazobenzenesulfonic acid and in the absence of sulfanilic acid, the reaction for either unconjugated or conjugated bilirubin proceeds in two successive first-order steps, the second step being much the slower. This study emphasizes the first step in the reaction for each species and includes data on the effects of p-diazobenzenesulfonic acid, albumin, benzoate, and caffeine concentrations, pH in the range from 4 to 12, and temperature. Mechanisms proposed for reactions with and without caffeine are used to develop rate equations, and the kinetic data are used to evaluate rate constants, acid dissociation constants for the different bilirubin species, and formation constants for bilirubin-caffeine complex species that are proposed.", "contents": "Kinetics of the reactions of unconjugated and conjugated bilirubins with p-diazobenzenesulfonic acid. We report the kinetics of the reactions of unconjugated bilirubin and conjugated bilirubin with p-diazobenzene sulfonic acid in aqueous media. Our studies confirm that each reaction proceeds in two steps and that the second step is catalyzed by sulfanilic acid. In the presence of an excess of p-diazobenzenesulfonic acid and in the absence of sulfanilic acid, the reaction for either unconjugated or conjugated bilirubin proceeds in two successive first-order steps, the second step being much the slower. This study emphasizes the first step in the reaction for each species and includes data on the effects of p-diazobenzenesulfonic acid, albumin, benzoate, and caffeine concentrations, pH in the range from 4 to 12, and temperature. Mechanisms proposed for reactions with and without caffeine are used to develop rate equations, and the kinetic data are used to evaluate rate constants, acid dissociation constants for the different bilirubin species, and formation constants for bilirubin-caffeine complex species that are proposed."}
{"id": "PMID:29721", "title": "Evaluation of a kinetic method for simultaneous determination of conjugated and unconjugated bilirubin.", "content": "This paper describes a fast kinetic method for the simultaneous determination of unconjugated and conjugated bilirugin in the same reaction solution. A stopped-flow mixing system with a stabilized photometer and small computer is used to mix sample and reagent rapidly and to record 250 data points during a 700-ms reaction time, and a regression program is used to resolve these kinetic data into the concentrations of unconjugated and conjugated bilirubin. Data are reported for synthetic single and two-component samples and for serum samples. Kinetic results for synthetic mixtures and serum samples are compared with results obtained by a conventional two-step procedure. Regression equations show good linearity between kinetically determined absorbance changes and concentration, good agreement between taken and found values for total, unconjugated, and conjugated bilirubin for synthetic samples in human serum albumin, and a good correlation between kinetic and equilibrium results for these species in sera. Regression slopes for kinetic vs. equilibrium assay results for total, unconjugated, and conjugated bilirubins in sera were 1.01 +/- 0.05, 1.04 +/- 0.03 and 0.91 +/- 0.04, respectively, with intercepts of 6.6,--2.7, and 3.8 micromol/liter, and standard errors of estimate of 28, 14, and 20 micromol/liter. These data reflect uncertainties in both the kinetic and equilibrium methods.", "contents": "Evaluation of a kinetic method for simultaneous determination of conjugated and unconjugated bilirubin. This paper describes a fast kinetic method for the simultaneous determination of unconjugated and conjugated bilirugin in the same reaction solution. A stopped-flow mixing system with a stabilized photometer and small computer is used to mix sample and reagent rapidly and to record 250 data points during a 700-ms reaction time, and a regression program is used to resolve these kinetic data into the concentrations of unconjugated and conjugated bilirubin. Data are reported for synthetic single and two-component samples and for serum samples. Kinetic results for synthetic mixtures and serum samples are compared with results obtained by a conventional two-step procedure. Regression equations show good linearity between kinetically determined absorbance changes and concentration, good agreement between taken and found values for total, unconjugated, and conjugated bilirubin for synthetic samples in human serum albumin, and a good correlation between kinetic and equilibrium results for these species in sera. Regression slopes for kinetic vs. equilibrium assay results for total, unconjugated, and conjugated bilirubins in sera were 1.01 +/- 0.05, 1.04 +/- 0.03 and 0.91 +/- 0.04, respectively, with intercepts of 6.6,--2.7, and 3.8 micromol/liter, and standard errors of estimate of 28, 14, and 20 micromol/liter. These data reflect uncertainties in both the kinetic and equilibrium methods."}
{"id": "PMID:29722", "title": "Characterization of the principal human prostatic acid phosphatase isoenzyme, purified by affinity chromatography and isoelectric focusing. Part II.", "content": "The principal enzyme of human prostatic acid phosphatase [orthophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2], which had been highly purified by affinity chromatography, isoelectric focusing, and gel filtrations, was shown to be homogeneous at pH 5.0 by sedimentation equilibrium analysis. The amino acid composition was determined and the sedimentation coefficient of the native molecule measured. The relative molecular mass was 89,000 at pH 5.0, as measured by analytical ultracentrifugation. The Km-value of the enzyme for p-nitrophenyl phosphate as substrate is 1.8-10(-4) mol/liter. I also examined substrate speificity, different inhibitors, and the effects of pH, temperature, and serum on the enzyme activity.", "contents": "Characterization of the principal human prostatic acid phosphatase isoenzyme, purified by affinity chromatography and isoelectric focusing. Part II. The principal enzyme of human prostatic acid phosphatase [orthophosphoric monoester phosphohydrolase (acid optimum), EC 3.1.3.2], which had been highly purified by affinity chromatography, isoelectric focusing, and gel filtrations, was shown to be homogeneous at pH 5.0 by sedimentation equilibrium analysis. The amino acid composition was determined and the sedimentation coefficient of the native molecule measured. The relative molecular mass was 89,000 at pH 5.0, as measured by analytical ultracentrifugation. The Km-value of the enzyme for p-nitrophenyl phosphate as substrate is 1.8-10(-4) mol/liter. I also examined substrate speificity, different inhibitors, and the effects of pH, temperature, and serum on the enzyme activity."}
{"id": "PMID:29723", "title": "Column-chromatographic separation of isoenzymes of aspartate aminotransferase.", "content": "We describe a column-chromatographic method for separating the mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase in human serum. Bed height of the ion exchanger, pH, and salt concentrations in the eluting buffers are shown to be variables affecting the separation of the isoenzymes. Under the optimized conditions selected for this study, a 30% increase in volume was observed in one fraction, associated with changing the salt concentration of the eluting buffer and attributed to a contraction of the DEAE-Sephadex A-50. Elution profiles (enzyme activity vs. fraction number) were examined with highly purified mitochondrial and cytoplasmic isoenzymes of human origin in bovine serum albumin and human serum. Recovery of the enzyme in the eluted fractions averaged 102% (SD, 2.0%) for specimens prepared from the purified isoenzymes and 104% (SD, 10.7%) for 38 human serum specimens. The separation technique showed linearity to catalytic concentrations in excess of 200 U/liter (reaction temperature 30 degrees C) for each isoenzyme. Additional information is presented regarding among-day precision and the effect of specimen dilution.", "contents": "Column-chromatographic separation of isoenzymes of aspartate aminotransferase. We describe a column-chromatographic method for separating the mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase in human serum. Bed height of the ion exchanger, pH, and salt concentrations in the eluting buffers are shown to be variables affecting the separation of the isoenzymes. Under the optimized conditions selected for this study, a 30% increase in volume was observed in one fraction, associated with changing the salt concentration of the eluting buffer and attributed to a contraction of the DEAE-Sephadex A-50. Elution profiles (enzyme activity vs. fraction number) were examined with highly purified mitochondrial and cytoplasmic isoenzymes of human origin in bovine serum albumin and human serum. Recovery of the enzyme in the eluted fractions averaged 102% (SD, 2.0%) for specimens prepared from the purified isoenzymes and 104% (SD, 10.7%) for 38 human serum specimens. The separation technique showed linearity to catalytic concentrations in excess of 200 U/liter (reaction temperature 30 degrees C) for each isoenzyme. Additional information is presented regarding among-day precision and the effect of specimen dilution."}
{"id": "PMID:29725", "title": "Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid.", "content": "Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid have been performed with a view to producing optimal assay conditions. Cholic acid-BSA was found to be the best immunogen to produce antibodies to conjugated cholic acid and the response was of an IgG type. Incorporating a spacer (hexanoic acid) between hapten and carrier protein resulted in a decrease in antiserum titre. Optimal conditions for the assay were found using [125I]histamine-glycocholic acid as ligand with a dilution of antiserum to produce 60% binding of ligand and a pH of 7.4. Using these assay conditions no serum effects were found; extraction of serum prior to assay was therefore unnecessary. The assay was sensitive enough to detect post-prandial increased in serum bile acid concentrations following a liquid test meal; no increase was observed throughout the same time period in a fasting control.", "contents": "Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid. Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid have been performed with a view to producing optimal assay conditions. Cholic acid-BSA was found to be the best immunogen to produce antibodies to conjugated cholic acid and the response was of an IgG type. Incorporating a spacer (hexanoic acid) between hapten and carrier protein resulted in a decrease in antiserum titre. Optimal conditions for the assay were found using [125I]histamine-glycocholic acid as ligand with a dilution of antiserum to produce 60% binding of ligand and a pH of 7.4. Using these assay conditions no serum effects were found; extraction of serum prior to assay was therefore unnecessary. The assay was sensitive enough to detect post-prandial increased in serum bile acid concentrations following a liquid test meal; no increase was observed throughout the same time period in a fasting control."}
{"id": "PMID:29726", "title": "Determination of cystyl-aminopeptidase. Isoenzymes in seminal plasma and serum of different origin.", "content": "The \"oxytocinase\" activity has been determined as the CAP (cystyl-aminopeptidase, EC 3.4.11.3) activity with several substrates. It was demonstrated that serum samples from pregnant women and patients with serious liver disease had increased CAP activities compared with normal serum. It was also shown that seminal plasma had very high CAP activity. The pH optimum for the enzymes from the various sources differed, as did the metal dependence. Furthermore, samples from patients with liver disease had higher CAP activities when assayed in buffers containing amino groups, in contrast to the other samples. Gel chromatography and gel electrophoresis revealed the presence of several isoenzymes. The serum from pregnant women contained an isoenzyme neither present in normal plasma nor in any of the other sources tested. It is possible that this isoenzymes represents the true oxytocinase. CAP and LAP (leucine aminopeptidase) activities were very well correlated in serum from pregnant women and seminal plasma, while the correlation for samples from patients with liver disease was not as good. When care was taken to determine the CAP activity at the right pH and with the appropriate buffer, the risk for interference from other enzymes was minimized in the determination of oxytocinase as CAP activity.", "contents": "Determination of cystyl-aminopeptidase. Isoenzymes in seminal plasma and serum of different origin. The \"oxytocinase\" activity has been determined as the CAP (cystyl-aminopeptidase, EC 3.4.11.3) activity with several substrates. It was demonstrated that serum samples from pregnant women and patients with serious liver disease had increased CAP activities compared with normal serum. It was also shown that seminal plasma had very high CAP activity. The pH optimum for the enzymes from the various sources differed, as did the metal dependence. Furthermore, samples from patients with liver disease had higher CAP activities when assayed in buffers containing amino groups, in contrast to the other samples. Gel chromatography and gel electrophoresis revealed the presence of several isoenzymes. The serum from pregnant women contained an isoenzyme neither present in normal plasma nor in any of the other sources tested. It is possible that this isoenzymes represents the true oxytocinase. CAP and LAP (leucine aminopeptidase) activities were very well correlated in serum from pregnant women and seminal plasma, while the correlation for samples from patients with liver disease was not as good. When care was taken to determine the CAP activity at the right pH and with the appropriate buffer, the risk for interference from other enzymes was minimized in the determination of oxytocinase as CAP activity."}
{"id": "PMID:29727", "title": "The activity of gamma-glutamyltransferase after bile duct ligation in guinea pig.", "content": "The activity of gamma-glutamyltransferase was studied in guinea pig after bile duct ligation. In serum, an abrupt increase in activity up to 10--20 times the normal value was found 3 h after obstruction and the mean activity over the first 3 days following the operation was some 8 times the normal value. In liver, however, a small decline in activity could be demonstrated. The administration of cycloheximide did not influence the acute increase in serum activity. Bile duct ligation caused marked increases in serum bile acid levels which initially paralleled the serum gamma-glutamyltransferase activity. It is suggested that the increased serum activity may arise from the solubilization by bile acids of liver membrane-bound enzyme.", "contents": "The activity of gamma-glutamyltransferase after bile duct ligation in guinea pig. The activity of gamma-glutamyltransferase was studied in guinea pig after bile duct ligation. In serum, an abrupt increase in activity up to 10--20 times the normal value was found 3 h after obstruction and the mean activity over the first 3 days following the operation was some 8 times the normal value. In liver, however, a small decline in activity could be demonstrated. The administration of cycloheximide did not influence the acute increase in serum activity. Bile duct ligation caused marked increases in serum bile acid levels which initially paralleled the serum gamma-glutamyltransferase activity. It is suggested that the increased serum activity may arise from the solubilization by bile acids of liver membrane-bound enzyme."}
{"id": "PMID:29728", "title": "[A new method for determination of cadmium in plasma (author's transl)].", "content": "Cadmium can be isolated from plasma by formation of negative charged iodide complexes bound to an anion exchange resin. Elution from the resin gives a cadmium solution with only a few interfering substances in an uniform matrix. Thus an undisturbed determination by flameless atomic absorption spectrometry is achieved. The mean of the natural cadmium level found in plasma was 1.9 +/- 0.8 ng/ml, within the normal range between 1.1 and 3.3 ng/ml.", "contents": "[A new method for determination of cadmium in plasma (author's transl)]. Cadmium can be isolated from plasma by formation of negative charged iodide complexes bound to an anion exchange resin. Elution from the resin gives a cadmium solution with only a few interfering substances in an uniform matrix. Thus an undisturbed determination by flameless atomic absorption spectrometry is achieved. The mean of the natural cadmium level found in plasma was 1.9 +/- 0.8 ng/ml, within the normal range between 1.1 and 3.3 ng/ml."}
{"id": "PMID:29729", "title": "Lactosyl ceramidosis: deficient activity of neutral beta-galactosidase in liver and cultivated fibroblasts?", "content": "Neutral beta-galactosidase was partially purified from liver of normal controls, a patient with Niemann-Pick disease type A and the previously described patient with lactosyl ceramidosis using Concanavalin A-Sepharose adsorption and Sephadex G-100 gel filtration. The partially purified fractions were essentially free of galactosyl ceramide beta-galactosidase and GM1 beta-galactosidase activities. The normal and Niemann-Pick fractions were found to hydrolyze lactosyl ceramide, in the presence of sodium taurodeoxycholate, at a pH optimum of 5.6 as well as aryl beta-galactosides and aryl beta-glucosides at pH 6.2. The corresponding fraction from the lactosyl ceramidosis liver contained only 1--4% of the normal activity towards artificial substrates and lactosyl ceramide. Cross-reacting material identical to the normal was demonstrated in this fraction with antiserum raised against purified neutral beta-galactosidase, but no activity was observed in the precipitin line when stained with naphthol AS-LC-beta-galactoside or naphthol AS-LC-beta-glucoside. A similar deficiency of neutral beta-galactosidase activity was demonstrated in cultivated fibroblasts of the patient with lactosyl ceramidosis. Following adsorption on Concanavalin A-Sepharose and anti-GM1 beta-galactosidase antibody-Sepharose conjugates and chromatography on DEAE cellulose, fibroblast lysates from the patient exhibited 3% of normal activity towards 4-methyl-umbelliferyl beta-glucoside at pH 6.2 and 12% of normal activity towards lactosyl ceramide at pH 5.6. These data suggest that neutral beta-galactosidase may have an in vivo role in the cleavage of lactosyl ceramide and that a deficiency of this activity may be related to the lactosyl ceramide accumulation observed in the patient with lactosyl ceramidosis.", "contents": "Lactosyl ceramidosis: deficient activity of neutral beta-galactosidase in liver and cultivated fibroblasts? Neutral beta-galactosidase was partially purified from liver of normal controls, a patient with Niemann-Pick disease type A and the previously described patient with lactosyl ceramidosis using Concanavalin A-Sepharose adsorption and Sephadex G-100 gel filtration. The partially purified fractions were essentially free of galactosyl ceramide beta-galactosidase and GM1 beta-galactosidase activities. The normal and Niemann-Pick fractions were found to hydrolyze lactosyl ceramide, in the presence of sodium taurodeoxycholate, at a pH optimum of 5.6 as well as aryl beta-galactosides and aryl beta-glucosides at pH 6.2. The corresponding fraction from the lactosyl ceramidosis liver contained only 1--4% of the normal activity towards artificial substrates and lactosyl ceramide. Cross-reacting material identical to the normal was demonstrated in this fraction with antiserum raised against purified neutral beta-galactosidase, but no activity was observed in the precipitin line when stained with naphthol AS-LC-beta-galactoside or naphthol AS-LC-beta-glucoside. A similar deficiency of neutral beta-galactosidase activity was demonstrated in cultivated fibroblasts of the patient with lactosyl ceramidosis. Following adsorption on Concanavalin A-Sepharose and anti-GM1 beta-galactosidase antibody-Sepharose conjugates and chromatography on DEAE cellulose, fibroblast lysates from the patient exhibited 3% of normal activity towards 4-methyl-umbelliferyl beta-glucoside at pH 6.2 and 12% of normal activity towards lactosyl ceramide at pH 5.6. These data suggest that neutral beta-galactosidase may have an in vivo role in the cleavage of lactosyl ceramide and that a deficiency of this activity may be related to the lactosyl ceramide accumulation observed in the patient with lactosyl ceramidosis."}
{"id": "PMID:29730", "title": "A simple UV spectrophotometric method for theophylline serum level determination.", "content": "A brief, simple and unexpensive UV spectrophotometric method for theophylline serum level determination is described. Charcoal extraction was performed for theophylline isolation from biological fluids. Coefficients of variation and recovery are similar to other parallel methods.", "contents": "A simple UV spectrophotometric method for theophylline serum level determination. A brief, simple and unexpensive UV spectrophotometric method for theophylline serum level determination is described. Charcoal extraction was performed for theophylline isolation from biological fluids. Coefficients of variation and recovery are similar to other parallel methods."}
{"id": "PMID:29732", "title": "Calcium ion as second messenger.", "content": "The role of calcium as an intracellular messenger in the activation of eukaryotic cells is discussed. Particular emphasis is devoted to: (1) the interrelationship between cell activation by chemical stimuli and alterations in intracellular calcium metabolism, and (2) the interrelated roles of calcium and the cyclic nucleotides, cyclic AMP and cyclic GMP, in achieving the final integrated, co-ordinated cellular response.", "contents": "Calcium ion as second messenger. The role of calcium as an intracellular messenger in the activation of eukaryotic cells is discussed. Particular emphasis is devoted to: (1) the interrelationship between cell activation by chemical stimuli and alterations in intracellular calcium metabolism, and (2) the interrelated roles of calcium and the cyclic nucleotides, cyclic AMP and cyclic GMP, in achieving the final integrated, co-ordinated cellular response."}
{"id": "PMID:29733", "title": "Evidence for secretion of vasoactive intestinal peptide by tumours of pancreas, adrenal medulla, thyroid and lung: support for the unifying APUD concept.", "content": "Levels of vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay in plasma or tissue from thirty-five patients with watery diarrhoea, and in plasma of twenty-five normal controls. Plasma levels were between 0.6 and 11.0 ng/ml in thirty-one of the thirty-three patients in whom it was measured and too low to measure (less than 200 pg/ml) in the other two. Peptide levels were less than 200 pg/ml in twenty-three of the controls, but higher in the remaining two. All tissues from patients were \"rich\" in VIP (10 ng to 35 microgram per g). The aetiologic diagnoses included pancreatic islet-cell adenoma or adenocarcinoma, islet-cell hyperplasia, bronchogenic carcinoma, pheochromocytoma, ganglioneuroblastoma, medullary thyroid carcinoma, and retroperitoneal histiocytoma. The findings support the conclusions that: (1) VIP is a likely mediator of the water-diarrhoea syndrome; (2) the syndrome may result from a variety of tumours; (3) this or a related peptide hormone may be secreted by these tumours; and (4) these tumours may have a common embryonic origin.", "contents": "Evidence for secretion of vasoactive intestinal peptide by tumours of pancreas, adrenal medulla, thyroid and lung: support for the unifying APUD concept. Levels of vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay in plasma or tissue from thirty-five patients with watery diarrhoea, and in plasma of twenty-five normal controls. Plasma levels were between 0.6 and 11.0 ng/ml in thirty-one of the thirty-three patients in whom it was measured and too low to measure (less than 200 pg/ml) in the other two. Peptide levels were less than 200 pg/ml in twenty-three of the controls, but higher in the remaining two. All tissues from patients were \"rich\" in VIP (10 ng to 35 microgram per g). The aetiologic diagnoses included pancreatic islet-cell adenoma or adenocarcinoma, islet-cell hyperplasia, bronchogenic carcinoma, pheochromocytoma, ganglioneuroblastoma, medullary thyroid carcinoma, and retroperitoneal histiocytoma. The findings support the conclusions that: (1) VIP is a likely mediator of the water-diarrhoea syndrome; (2) the syndrome may result from a variety of tumours; (3) this or a related peptide hormone may be secreted by these tumours; and (4) these tumours may have a common embryonic origin."}
{"id": "PMID:29734", "title": "Neuroendocrine embryology and the APUD concept.", "content": "In the Vertebrata the great majority of cells producing hormonal peptides belong to the APUD series and share its distinctive cytochemical and ultrastructural characteristics. According to the concept all members of the series are to be regarded as derivatives of neuroectoderm or of specialized (placodal) ectoderm. For most of the APUD cells this criterion is fulfilled in that their origin from neural tube, neural ridges or neural crest can be considered proven. Complete proof is not yet available for the APUD cells of the gastrointestinal tract and pancreas, and indeed much contrary evidence can be cited. Despite the latter, our embryological studies show: (1) that the hypothalamohypophyseal complex is wholly neuroectodermal; (2)that the chronology of neural crest dispersion is such that this tissue could be responsible for observed APUD cell contributions to the foregut; (3) that placodal ectoderm makes important contributions to pharyngeal pouch endocrine derivatives in birds and mammals; and (4) that the amphibian parathyroid gland is derived from the same layer of neural ectoderm as the hypothalamo-hypophyseal axis. Supporting immunocytochemical studies indicate that peptides belonging to the APUD series are more widely distributed than hitherto recognized and it is concluded: (1) that the whole of peptide endocrinology is neuroendocrinology; and (2) that the APUD cells, with a few cells hitherto regarded as being outside the series, form a third (Endocrine) division of the nervous system to add to the existing Somatic and Autonomic divisions.", "contents": "Neuroendocrine embryology and the APUD concept. In the Vertebrata the great majority of cells producing hormonal peptides belong to the APUD series and share its distinctive cytochemical and ultrastructural characteristics. According to the concept all members of the series are to be regarded as derivatives of neuroectoderm or of specialized (placodal) ectoderm. For most of the APUD cells this criterion is fulfilled in that their origin from neural tube, neural ridges or neural crest can be considered proven. Complete proof is not yet available for the APUD cells of the gastrointestinal tract and pancreas, and indeed much contrary evidence can be cited. Despite the latter, our embryological studies show: (1) that the hypothalamohypophyseal complex is wholly neuroectodermal; (2)that the chronology of neural crest dispersion is such that this tissue could be responsible for observed APUD cell contributions to the foregut; (3) that placodal ectoderm makes important contributions to pharyngeal pouch endocrine derivatives in birds and mammals; and (4) that the amphibian parathyroid gland is derived from the same layer of neural ectoderm as the hypothalamo-hypophyseal axis. Supporting immunocytochemical studies indicate that peptides belonging to the APUD series are more widely distributed than hitherto recognized and it is concluded: (1) that the whole of peptide endocrinology is neuroendocrinology; and (2) that the APUD cells, with a few cells hitherto regarded as being outside the series, form a third (Endocrine) division of the nervous system to add to the existing Somatic and Autonomic divisions."}
{"id": "PMID:29735", "title": "The development of the releasing factor concept.", "content": "After four decades of intense and competitive research, three hypothalamic releasing hormones (formerly factors) have recently been isolated and characterized. These are the decapeptide gonadotrophin releasing hormone (GnRH), tripeptide thyrotrophin releasing hormone (TRH), and the tetradecapeptide somatostatin. Some aspects of these hormones are discussed, and GnRH is considered in greater detail to demonstrate the difficulties involved in fulfilling completely the criteria which determine whether a substance can be accepted as a physiological releasing hormone. A substance immunologically similar to GnRH is present in rat hypophysial portal vessel blood, but, while the amount of this substance released into the portal circulation can be increased significantly by electrical stimulation of the preoptic area, no significant changes occur during the oestrous cycle or after long-term castration. This may be due to interference with the normal secretion of GnRH by the trauma and anaesthesia which necessarily accompany exposure of the pituitary stalk. However, the possibility exists that our preconceived notions regarding the changes in plasma levels of releasing hormones under physiological conditions may be incorrect. Thus it seems likely that changes in the rate of secretion of thyrotrophin is effected by throid hormones modulating the responsiveness of the thyrotrophs to a steady input of TRH. Evidence is presented for the existence of a similar mechanism for gonadotrophin secretion, and the role of steroid hormones and the priming effect of GnRH in modulating the responsiveness of the gonadotrophs is considered. The intrinsic connexions of the hypothalamus, the role of the hypothalamic aminergic systems and the autonomy of the hypothalamus with respect to anterior pituitary control present many problems which will prove difficult to solve.", "contents": "The development of the releasing factor concept. After four decades of intense and competitive research, three hypothalamic releasing hormones (formerly factors) have recently been isolated and characterized. These are the decapeptide gonadotrophin releasing hormone (GnRH), tripeptide thyrotrophin releasing hormone (TRH), and the tetradecapeptide somatostatin. Some aspects of these hormones are discussed, and GnRH is considered in greater detail to demonstrate the difficulties involved in fulfilling completely the criteria which determine whether a substance can be accepted as a physiological releasing hormone. A substance immunologically similar to GnRH is present in rat hypophysial portal vessel blood, but, while the amount of this substance released into the portal circulation can be increased significantly by electrical stimulation of the preoptic area, no significant changes occur during the oestrous cycle or after long-term castration. This may be due to interference with the normal secretion of GnRH by the trauma and anaesthesia which necessarily accompany exposure of the pituitary stalk. However, the possibility exists that our preconceived notions regarding the changes in plasma levels of releasing hormones under physiological conditions may be incorrect. Thus it seems likely that changes in the rate of secretion of thyrotrophin is effected by throid hormones modulating the responsiveness of the thyrotrophs to a steady input of TRH. Evidence is presented for the existence of a similar mechanism for gonadotrophin secretion, and the role of steroid hormones and the priming effect of GnRH in modulating the responsiveness of the gonadotrophs is considered. The intrinsic connexions of the hypothalamus, the role of the hypothalamic aminergic systems and the autonomy of the hypothalamus with respect to anterior pituitary control present many problems which will prove difficult to solve."}
{"id": "PMID:29737", "title": "The influence of dialysis fluid composition on the blood pressure response during dialysis.", "content": "To elucidate the relative role of osmolar (sodium) and acetate shifts during dialysis, 6 patients with problems of overhydration underwent rapid ultrafiltration for 1 hr (mean weight reduction 2.0 kg), using the 1 m2 RP 6 dialyzer. Ultrafiltration was carried out at the beginning of each of 5 dialysis treatments at weekly intervals. Ultrafiltration was undertaken without dialysis (controls) and with simultaneous dialysis using acetate (40 mmoles/1) or bicarbonate (25 mmoles/1) in the dialysis fluid with dialyzate sodium concentration of 133 and 145 mmoles/1. The systolic blood pressure and mean arterial pressure which were stable with ultrafiltration only fell slightly when a high dialyzate sodium concentration was used and much further when the dialyzate sodium concentration was kept low. These changes were apparently related to the changes in plasma osmolality. Acetate had no effect on blood pressure at the higher sodium concentration, but a slight (insignificant) additive effect when used in the low-sodium dialyzate. Shifts in osmolality (sodium concentration) seem to be more important than the effect of acetate in inducing dialysis-associated hypotension.", "contents": "The influence of dialysis fluid composition on the blood pressure response during dialysis. To elucidate the relative role of osmolar (sodium) and acetate shifts during dialysis, 6 patients with problems of overhydration underwent rapid ultrafiltration for 1 hr (mean weight reduction 2.0 kg), using the 1 m2 RP 6 dialyzer. Ultrafiltration was carried out at the beginning of each of 5 dialysis treatments at weekly intervals. Ultrafiltration was undertaken without dialysis (controls) and with simultaneous dialysis using acetate (40 mmoles/1) or bicarbonate (25 mmoles/1) in the dialysis fluid with dialyzate sodium concentration of 133 and 145 mmoles/1. The systolic blood pressure and mean arterial pressure which were stable with ultrafiltration only fell slightly when a high dialyzate sodium concentration was used and much further when the dialyzate sodium concentration was kept low. These changes were apparently related to the changes in plasma osmolality. Acetate had no effect on blood pressure at the higher sodium concentration, but a slight (insignificant) additive effect when used in the low-sodium dialyzate. Shifts in osmolality (sodium concentration) seem to be more important than the effect of acetate in inducing dialysis-associated hypotension."}
{"id": "PMID:29738", "title": "Drug concentration in saliva.", "content": "It is possible to predict plasma concentrations of drugs by measurement in saliva, obviating the need for venipuncture. Using a selection of weakly acidic and basic drugs, we have found this prediction reliable for drugs largely nonionized at normal plasma pH (phenytoin, phenobarbital, antipyrine) but unreliable for ionized drugs (chlorpropramide, tolbutamide, propranolol, meperidine). Deliberate alteration of saliva flow rate and pH using different stimuli have produced twofold changes in saliva drug concentrations. Wide interindividual variability of saliva pH is the likely explanation for the inconstancy of saliva to plasma concentration ratios for ionized drugs.", "contents": "Drug concentration in saliva. It is possible to predict plasma concentrations of drugs by measurement in saliva, obviating the need for venipuncture. Using a selection of weakly acidic and basic drugs, we have found this prediction reliable for drugs largely nonionized at normal plasma pH (phenytoin, phenobarbital, antipyrine) but unreliable for ionized drugs (chlorpropramide, tolbutamide, propranolol, meperidine). Deliberate alteration of saliva flow rate and pH using different stimuli have produced twofold changes in saliva drug concentrations. Wide interindividual variability of saliva pH is the likely explanation for the inconstancy of saliva to plasma concentration ratios for ionized drugs."}
{"id": "PMID:29739", "title": "Interaction of disulfiram with benzodiazepines.", "content": "The disposition of chlordiazepoxide (50 mg, intravenously), diazepam (0.143 mg/kg, orally), and oxazepam (0.429 mg/kg, orally) were studied in normal and alcoholic men before and after chronic disulfiram administration. Decreases in the plasma clearance of chlordiazepoxide (54%, p less than 0.05), diazepam (41%, p less than 0.05), and their active N-desmethyl metabolites were observed. Oxazepam has no important active metabolites and its net disposition is minimally altered by disulfiram. Oxazepam disposition is unaffected by age and liver disease. These considerations together with that of the short half-life of oxazepam (median, 6.1 hr) suggest that oxazepam may be the drug of choice if benzodiazepine therapy is used for patients taking disulfiram.", "contents": "Interaction of disulfiram with benzodiazepines. The disposition of chlordiazepoxide (50 mg, intravenously), diazepam (0.143 mg/kg, orally), and oxazepam (0.429 mg/kg, orally) were studied in normal and alcoholic men before and after chronic disulfiram administration. Decreases in the plasma clearance of chlordiazepoxide (54%, p less than 0.05), diazepam (41%, p less than 0.05), and their active N-desmethyl metabolites were observed. Oxazepam has no important active metabolites and its net disposition is minimally altered by disulfiram. Oxazepam disposition is unaffected by age and liver disease. These considerations together with that of the short half-life of oxazepam (median, 6.1 hr) suggest that oxazepam may be the drug of choice if benzodiazepine therapy is used for patients taking disulfiram."}
{"id": "PMID:29740", "title": "(-)-2-Hydroxy-n-cyclopropylmethylmorphinan: radioimmunoassay and phamacokinetic profile.", "content": "The pharmacokinetic profile of (-)-2-hydroxy-N-cyclopropylmethylmorphinan (HCMM), a narcotic antagonist and analgesic, has been evaluated in man following administration of 25 to 50 mg of the drug orally and 10 to 15 mg intramuscularly. A specific radioimmunoassay procedure was developed for the determination of HCMM in plasma and urine. The drug had a mean \"apparent\" elimination half-life in plasma of about 11 hr following both routes of administration. A mean of 47% of the oral dose was excreted in the urine as unconjugated and conjugated HCMM and only 5% of the dose was excreted as intact HCMM. In one subject studied, the plasma levels of conjugated HCMM were as much as 5-fold higher than the levels of unconjugated drug. Although there was considerable intersubject variability following both routes of administration, the overall pharmacokinetic parameters suggest that oral and intramuscular doses are bioequivalent.", "contents": "(-)-2-Hydroxy-n-cyclopropylmethylmorphinan: radioimmunoassay and phamacokinetic profile. The pharmacokinetic profile of (-)-2-hydroxy-N-cyclopropylmethylmorphinan (HCMM), a narcotic antagonist and analgesic, has been evaluated in man following administration of 25 to 50 mg of the drug orally and 10 to 15 mg intramuscularly. A specific radioimmunoassay procedure was developed for the determination of HCMM in plasma and urine. The drug had a mean \"apparent\" elimination half-life in plasma of about 11 hr following both routes of administration. A mean of 47% of the oral dose was excreted in the urine as unconjugated and conjugated HCMM and only 5% of the dose was excreted as intact HCMM. In one subject studied, the plasma levels of conjugated HCMM were as much as 5-fold higher than the levels of unconjugated drug. Although there was considerable intersubject variability following both routes of administration, the overall pharmacokinetic parameters suggest that oral and intramuscular doses are bioequivalent."}
{"id": "PMID:29741", "title": "Effects of the beta-receptor antagonists propranolol, oxprenolol and labetalol on human vascular smooth-muscle contraction.", "content": "1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.", "contents": "Effects of the beta-receptor antagonists propranolol, oxprenolol and labetalol on human vascular smooth-muscle contraction. 1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant."}
{"id": "PMID:29736", "title": "Differential blockade of octopamine and dopamine receptors by analogues of clozapine and metoclopramide.", "content": "1. Sulpiride, but not procainamide, antagonizes the excitatory effects of (+/-)-octopamine receptors in the Tapes ventricle. Neither compound attenuates dopamine excitation. 2. Clozapine will attenuate the effects of (+/-)-octopamine and (-)-alpha-methyl octopamine at the octopamine receptor but not the excitatory effect of dopamine at dopamine receptors. 3. Clozapine is more potent than its 2-positional isomer HF 2046 in attenuating octopamine excitation. However, HF 2046, unlike clozapine, will attenuate the excitatory effects of dopamine. 4. These data indicate that replacement of the 8-chloro substituent in the clozapine nucleus with a 2-chloro substituent decreases the ability of the compound to blockaed octopamine receptors. However, the 2-chloro-substituted compound (HF 2046) now has the added ability to blockade excitatory dopamine receptors. 5. The greater potency of clozapine than HF 2046 as an octopamine antagonist suggests that it is the 8-chloro-substituted aromatic ring of clozapine which overlaps the aromatic site usually occupied by the octopamine aromatic ring.", "contents": "Differential blockade of octopamine and dopamine receptors by analogues of clozapine and metoclopramide. 1. Sulpiride, but not procainamide, antagonizes the excitatory effects of (+/-)-octopamine receptors in the Tapes ventricle. Neither compound attenuates dopamine excitation. 2. Clozapine will attenuate the effects of (+/-)-octopamine and (-)-alpha-methyl octopamine at the octopamine receptor but not the excitatory effect of dopamine at dopamine receptors. 3. Clozapine is more potent than its 2-positional isomer HF 2046 in attenuating octopamine excitation. However, HF 2046, unlike clozapine, will attenuate the excitatory effects of dopamine. 4. These data indicate that replacement of the 8-chloro substituent in the clozapine nucleus with a 2-chloro substituent decreases the ability of the compound to blockaed octopamine receptors. However, the 2-chloro-substituted compound (HF 2046) now has the added ability to blockade excitatory dopamine receptors. 5. The greater potency of clozapine than HF 2046 as an octopamine antagonist suggests that it is the 8-chloro-substituted aromatic ring of clozapine which overlaps the aromatic site usually occupied by the octopamine aromatic ring."}
{"id": "PMID:29744", "title": "Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. A patient with four episodes treated without use of a respirator.", "content": "A 51-year-old woman with chronic respiratory failure (status after tuberculosis) was given an infusion of doxapram hydrochloride (1 to 2 mg/kg of body weight per hour) for four episodes of acute exacerbation of her condition. Treatment with the drug prevented worsening of hypercapnia in the four episodes, when administration of 24 percent oxygen had occasioned rises in the arterial carbon dioxide tension of 23, 10, 9, and 7 mm Hg.", "contents": "Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. A patient with four episodes treated without use of a respirator. A 51-year-old woman with chronic respiratory failure (status after tuberculosis) was given an infusion of doxapram hydrochloride (1 to 2 mg/kg of body weight per hour) for four episodes of acute exacerbation of her condition. Treatment with the drug prevented worsening of hypercapnia in the four episodes, when administration of 24 percent oxygen had occasioned rises in the arterial carbon dioxide tension of 23, 10, 9, and 7 mm Hg."}
{"id": "PMID:29748", "title": "[Scanning electromicroscopic studies of the surface of teeth. I. After manual treatment with tooth cleansers. II. Tooth cleaning with power-driven instruments].", "content": "Scanning electron microscopic examination of tooth surfaces after using manually operated instruments to remove calculus showed distinct lesions on the hard substances of the tooth. The extent of damage depends considerably on the area of the tooth treated (the border between the enamel and the cementum is particularly endangered), the amount of force used, and the length of time required for treatment. Examination of tooth surfaces following application of various types of power-driven scaling instruments revealed that lesions of the hard substances on the tooth are possible. The extent of the damage depends on several different factors, particularly the pressure applied and the area of the tooth treated. The border between the enamel and the cementum is particulary endangered.", "contents": "[Scanning electromicroscopic studies of the surface of teeth. I. After manual treatment with tooth cleansers. II. Tooth cleaning with power-driven instruments]. Scanning electron microscopic examination of tooth surfaces after using manually operated instruments to remove calculus showed distinct lesions on the hard substances of the tooth. The extent of damage depends considerably on the area of the tooth treated (the border between the enamel and the cementum is particularly endangered), the amount of force used, and the length of time required for treatment. Examination of tooth surfaces following application of various types of power-driven scaling instruments revealed that lesions of the hard substances on the tooth are possible. The extent of the damage depends on several different factors, particularly the pressure applied and the area of the tooth treated. The border between the enamel and the cementum is particulary endangered."}
{"id": "PMID:29749", "title": "[In vitro demethylation with a NADPH-generating system containing rat cytosol enzymes].", "content": "The author uses during demethylization in vitro two types of NADPH-generating systems: 1) postmitochondrial supernatant, whose disadvantage is that in vivo effects the cause for changes in demethylization could be due both to microsomes and dehydrogenases: 2) imported purified enzymic preparations, which is connected with supplying difficulties. The author proposes the usage of postmicrosomal supernatant (cytosol) from rats' liver to overcome these disadvantages. This fraction is with very good efficiency compared with that of the imported purified enzymes. The isolated cytosol, preserved at -10 degrees keeps its initial activity for a period of three days, but after or six days the diminition of the enzymic activity could be compensated by using simultaneously two substrates-isocytrate and glucose-6-phosphate for demethylizating systems.", "contents": "[In vitro demethylation with a NADPH-generating system containing rat cytosol enzymes]. The author uses during demethylization in vitro two types of NADPH-generating systems: 1) postmitochondrial supernatant, whose disadvantage is that in vivo effects the cause for changes in demethylization could be due both to microsomes and dehydrogenases: 2) imported purified enzymic preparations, which is connected with supplying difficulties. The author proposes the usage of postmicrosomal supernatant (cytosol) from rats' liver to overcome these disadvantages. This fraction is with very good efficiency compared with that of the imported purified enzymes. The isolated cytosol, preserved at -10 degrees keeps its initial activity for a period of three days, but after or six days the diminition of the enzymic activity could be compensated by using simultaneously two substrates-isocytrate and glucose-6-phosphate for demethylizating systems."}
{"id": "PMID:29750", "title": "Premedication for upper gastrointestinal endoscopy: a comparative study of flunitrazepam, diazepam and neuroleptanalgesia.", "content": "Flunitrazepam or diazepam with atropine and a combination of phenoperidine, droperidol and cyclizine (neuroleptanalgesia) were compared as premedication in three groups of 25 patients undergoing routine upper gastrointestinal endoscopy. Drug doses were titrated carefully against response and all three regimes were found to be similar in terms of safety, patient co-operation, relaxation and speed of recovery. Neuroleptanalgesia however produced a statistically significant rise in endtidal pCO2 and systolic blood pressure. The benzodiazepines, and in particular flunitrazepam, produced a significantly greater amnesia for the procedure, patients given these drugs being more willing to undergo repeat endoscopy.", "contents": "Premedication for upper gastrointestinal endoscopy: a comparative study of flunitrazepam, diazepam and neuroleptanalgesia. Flunitrazepam or diazepam with atropine and a combination of phenoperidine, droperidol and cyclizine (neuroleptanalgesia) were compared as premedication in three groups of 25 patients undergoing routine upper gastrointestinal endoscopy. Drug doses were titrated carefully against response and all three regimes were found to be similar in terms of safety, patient co-operation, relaxation and speed of recovery. Neuroleptanalgesia however produced a statistically significant rise in endtidal pCO2 and systolic blood pressure. The benzodiazepines, and in particular flunitrazepam, produced a significantly greater amnesia for the procedure, patients given these drugs being more willing to undergo repeat endoscopy."}
{"id": "PMID:29753", "title": "Amino-acid sequence of toxin I from Anemonia sulcata.", "content": "Toxin I from Anemonia sulcata, a major component of the sea anemone venom, consists of 46 amino acid residues which are linked by three disulfide bridges. The [14C]carboxymethylated polypeptide was sequenced to position 29 by automated Edman degradation. The remaining sequence was determined from cyanogen bromide peptides and from tryptic peptides of the citraconylated [14C]carboxymethylated toxin. Toxin I is homologous to toxin II from Anemonia sulcata and to anthopleurin A, a toxin from the sea anemone Anthopleura xanthogrammica. These toxins constitute a new class of polypeptide toxins. No significant homologies exist with toxin III from Anemonia sulcata nor with known sequences of neurotoxins or cardiotoxins of various origin.", "contents": "Amino-acid sequence of toxin I from Anemonia sulcata. Toxin I from Anemonia sulcata, a major component of the sea anemone venom, consists of 46 amino acid residues which are linked by three disulfide bridges. The [14C]carboxymethylated polypeptide was sequenced to position 29 by automated Edman degradation. The remaining sequence was determined from cyanogen bromide peptides and from tryptic peptides of the citraconylated [14C]carboxymethylated toxin. Toxin I is homologous to toxin II from Anemonia sulcata and to anthopleurin A, a toxin from the sea anemone Anthopleura xanthogrammica. These toxins constitute a new class of polypeptide toxins. No significant homologies exist with toxin III from Anemonia sulcata nor with known sequences of neurotoxins or cardiotoxins of various origin."}
{"id": "PMID:29754", "title": "The proton pump of cytochrome c oxidase and its stoichiometry.", "content": "The operation of cytochrome c oxidase with ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine as substrate in antimycin-A-inhibited rat liver mitochondria is coupled to proton ejection. Measurements of the initial rate of valinomycin-dependent K+ uptake have shown that nearly 4 K+ are taken up as 2 electrons are transferred from cytochrome c to oxygen. This proves directly that a charge separation of nearly 4 occurs across the inner mitochondrial membrane each time 2 electrons are transferred to oxygen. Measurements of the initial rate of proton movement after addition of the reductant show that about 1.6 protons are released by the mitochondria as 2 electrons are transferred from cytochrome c to oxygen. The data support the suggestion of a proton pump coupled to the operation of cytochrome c oxidase [Wikstr\u00f6m, M. F. K. (1977) Nature (Lond.) 266, 271--273].", "contents": "The proton pump of cytochrome c oxidase and its stoichiometry. The operation of cytochrome c oxidase with ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine as substrate in antimycin-A-inhibited rat liver mitochondria is coupled to proton ejection. Measurements of the initial rate of valinomycin-dependent K+ uptake have shown that nearly 4 K+ are taken up as 2 electrons are transferred from cytochrome c to oxygen. This proves directly that a charge separation of nearly 4 occurs across the inner mitochondrial membrane each time 2 electrons are transferred to oxygen. Measurements of the initial rate of proton movement after addition of the reductant show that about 1.6 protons are released by the mitochondria as 2 electrons are transferred from cytochrome c to oxygen. The data support the suggestion of a proton pump coupled to the operation of cytochrome c oxidase [Wikstr\u00f6m, M. F. K. (1977) Nature (Lond.) 266, 271--273]."}
{"id": "PMID:29755", "title": "Potassium uniport and ATP synthesis in Halobacterium halobium.", "content": "Light-driven potassium ion uptake in Halobacterium halobium is mediated by bacteriorhodopsin. This uptake is charge-balanced by sodium ions and not by proton release. Light-induced shifts in concentrations of divalent cations were found to be negligible. The transient changes in extracellular pH (alkaline overshoot) can be understood by the concomitant processes of ATP synthesis, proton/sodium exchange and potassium uptake. The driving force of potassium ion uptake is the membrane potential, no ATP-dependent potassium transport process is found. Fluorescence measurements indicate a high permeability of the membrane to potassium ions compared to sodium ions. Therefore the potassium ion diffusion potential contributes to the membrane potential (about 30 mV/decade) and thereby influences the ATP level. Sudden enhancement of the diffusion potential by the potassium ionophore monactin leads to the expected transient increase in cellular ATP level. Due to the large size (up to 100-fold) of the potassium ion gradient and its high capacity (intracellular concentration up to 3 M) the potassium ion gradient can well serve the cell as a long term storage form of energy.", "contents": "Potassium uniport and ATP synthesis in Halobacterium halobium. Light-driven potassium ion uptake in Halobacterium halobium is mediated by bacteriorhodopsin. This uptake is charge-balanced by sodium ions and not by proton release. Light-induced shifts in concentrations of divalent cations were found to be negligible. The transient changes in extracellular pH (alkaline overshoot) can be understood by the concomitant processes of ATP synthesis, proton/sodium exchange and potassium uptake. The driving force of potassium ion uptake is the membrane potential, no ATP-dependent potassium transport process is found. Fluorescence measurements indicate a high permeability of the membrane to potassium ions compared to sodium ions. Therefore the potassium ion diffusion potential contributes to the membrane potential (about 30 mV/decade) and thereby influences the ATP level. Sudden enhancement of the diffusion potential by the potassium ionophore monactin leads to the expected transient increase in cellular ATP level. Due to the large size (up to 100-fold) of the potassium ion gradient and its high capacity (intracellular concentration up to 3 M) the potassium ion gradient can well serve the cell as a long term storage form of energy."}
{"id": "PMID:29757", "title": "The glutamine synthetase from Azotobacter vinelandii: purification, characterization, regulation and localization.", "content": "The glutamine synthetase (EC 6.3.1.2) from the N2-fixing bacterium Azotobacter vinelandii was purified to homogeneity by heat treatment, ammonium sulfate precipitation and ion-exchange chromatography. The following molecular parameters were determined: molecular weight 640 000, subunit molecular weight 53 000, partial specific volume 0.710 cm3/g, isoelectric point 4.6, amino acid composition. Most of the molecules are composed of 12 identical subunits but active oligomers of other degrees of polymerization, apparently aggregates with 8, 10 and 24 subunits, were also detected to a lesser extent. The enzymatic activity is regulated via adenylylation-deadenylylation cycles: liberation of AMP was detected upon treatment of the adenylylated form with phosphodiesterase along with a change in the catalytic properties. Adenylylation in vivo is specifically induced by high extracellular ammonia levels. The Km values for the Mg2+-dependent formation of glutamine were independent of the degree of adenylylation for glutamate and ATP, but varied for ammonia. Furthermore the catalytic activity is regulated by several nitrogenous feedback inhibitors. The degree of inhibition in some cases was dependent on the substrate concentrations: the sensitivity towards glycine, alanine and serine decreased with a decreasing ammonia level, while the sensitivity towards ADP or AMP increased with a decreasing ATP concentration. Part of the enzyme (about 30%) seems to be attached to the plasma membrane while the main fraction is found in the cytosol.", "contents": "The glutamine synthetase from Azotobacter vinelandii: purification, characterization, regulation and localization. The glutamine synthetase (EC 6.3.1.2) from the N2-fixing bacterium Azotobacter vinelandii was purified to homogeneity by heat treatment, ammonium sulfate precipitation and ion-exchange chromatography. The following molecular parameters were determined: molecular weight 640 000, subunit molecular weight 53 000, partial specific volume 0.710 cm3/g, isoelectric point 4.6, amino acid composition. Most of the molecules are composed of 12 identical subunits but active oligomers of other degrees of polymerization, apparently aggregates with 8, 10 and 24 subunits, were also detected to a lesser extent. The enzymatic activity is regulated via adenylylation-deadenylylation cycles: liberation of AMP was detected upon treatment of the adenylylated form with phosphodiesterase along with a change in the catalytic properties. Adenylylation in vivo is specifically induced by high extracellular ammonia levels. The Km values for the Mg2+-dependent formation of glutamine were independent of the degree of adenylylation for glutamate and ATP, but varied for ammonia. Furthermore the catalytic activity is regulated by several nitrogenous feedback inhibitors. The degree of inhibition in some cases was dependent on the substrate concentrations: the sensitivity towards glycine, alanine and serine decreased with a decreasing ammonia level, while the sensitivity towards ADP or AMP increased with a decreasing ATP concentration. Part of the enzyme (about 30%) seems to be attached to the plasma membrane while the main fraction is found in the cytosol."}
{"id": "PMID:29758", "title": "Benzamides and classical neuroleptics: comparison of their actions using 6 apomorphine-induced effects.", "content": "The effects of 6 benzamides and 8 classical neuroleptics were studied on 6 different apomorphine-induced effects. These drugs did not antagonize all the effects in the same way. The differences are discussed according to the two types of dopaminergic receptor hypothesis. Some apomorphine-induced effects (stereotyped behavior, circling behavior, climbing behavior, and increased motor activity) could be related to stimulation of one type of dopaminergic receptor, other effects (hypothermia and decreased activity) to the other type. Pimozide, sulpiride, thioproperazine, GRI 1665 and TER 1546, could block selectively one type of dopaminergic receptor, at least in a given range of doses. Clozapine, chlorpromazine, levomepromazine, and thioridazine, could block selectively the other type of dopaminergic receptor. Haloperidol, metoclopramide, prochlorperazine, sultopride, and tiapride, could block both types of dopaminergic receptors with equal intensity whatever the dose.", "contents": "Benzamides and classical neuroleptics: comparison of their actions using 6 apomorphine-induced effects. The effects of 6 benzamides and 8 classical neuroleptics were studied on 6 different apomorphine-induced effects. These drugs did not antagonize all the effects in the same way. The differences are discussed according to the two types of dopaminergic receptor hypothesis. Some apomorphine-induced effects (stereotyped behavior, circling behavior, climbing behavior, and increased motor activity) could be related to stimulation of one type of dopaminergic receptor, other effects (hypothermia and decreased activity) to the other type. Pimozide, sulpiride, thioproperazine, GRI 1665 and TER 1546, could block selectively one type of dopaminergic receptor, at least in a given range of doses. Clozapine, chlorpromazine, levomepromazine, and thioridazine, could block selectively the other type of dopaminergic receptor. Haloperidol, metoclopramide, prochlorperazine, sultopride, and tiapride, could block both types of dopaminergic receptors with equal intensity whatever the dose."}
{"id": "PMID:29759", "title": "Regional localization of halopemide, a new psychotropic agent, in the rat brain.", "content": "Halopemide is a new psychotropic agent, structurally related to the neuroleptics of the butyrophenone type, but with a different phamacological and clinical profile. The concentration of halopemide in the rat brain is about 10 times less than that of R29800, its chemical congener and of spiperone, both typical neuroleptics. In the pituitary gland, however, the levels are the same. The distribution profile of halopemide in rat brain deviates from that of neuroleptics. The highest level of halopemide is found in septal and thalamic areas whereas the neuroleptics are concentrated in the caudate nucleus, the nucleus accumbens and the tuberculum olfactorium. Subcellular distribution experiments show that in the caudate nucleus halopemide is far less particle-bound that are the neuroleptic agents.", "contents": "Regional localization of halopemide, a new psychotropic agent, in the rat brain. Halopemide is a new psychotropic agent, structurally related to the neuroleptics of the butyrophenone type, but with a different phamacological and clinical profile. The concentration of halopemide in the rat brain is about 10 times less than that of R29800, its chemical congener and of spiperone, both typical neuroleptics. In the pituitary gland, however, the levels are the same. The distribution profile of halopemide in rat brain deviates from that of neuroleptics. The highest level of halopemide is found in septal and thalamic areas whereas the neuroleptics are concentrated in the caudate nucleus, the nucleus accumbens and the tuberculum olfactorium. Subcellular distribution experiments show that in the caudate nucleus halopemide is far less particle-bound that are the neuroleptic agents."}
{"id": "PMID:29761", "title": "Mianserin--an analysis of its peripheral autonomic actions.", "content": "The autonomic profile of mianserin has been compared with that of yohimbine, phentolamine, phenoxybenzamine and desmethylimipramine. The effects of mianserin on tyramine and noradrenaline pressor responses in the pithed rat were consistent with alpha-adrenoceptor antagonist and uptake blocking properties. In isolated tissue experiments, the selectivity of mianserin for pre- and postsynaptic alpha-adrenoceptors was similar to that of phentolamine. In pitched rats mianserin antagonised the pressor response produced by clonidine and reversed the inhibitory actions of clonidine on cardiac nerve stimulation. In contrast mianserin only caused slight reversal of the inhibitory effects of clonidine on hypogastric nerve stimulation. Uptake blockade itself inhibits hypogastric nerve stimulation and this could counteract any antagonism of the effects of clonidine at the presynaptic alpha-adrenoceptor. The results demonstrate the uptake blocking properties of mianserin and its antagonism at both pre- and postsynaptic alpha-adrenoceptors.", "contents": "Mianserin--an analysis of its peripheral autonomic actions. The autonomic profile of mianserin has been compared with that of yohimbine, phentolamine, phenoxybenzamine and desmethylimipramine. The effects of mianserin on tyramine and noradrenaline pressor responses in the pithed rat were consistent with alpha-adrenoceptor antagonist and uptake blocking properties. In isolated tissue experiments, the selectivity of mianserin for pre- and postsynaptic alpha-adrenoceptors was similar to that of phentolamine. In pitched rats mianserin antagonised the pressor response produced by clonidine and reversed the inhibitory actions of clonidine on cardiac nerve stimulation. In contrast mianserin only caused slight reversal of the inhibitory effects of clonidine on hypogastric nerve stimulation. Uptake blockade itself inhibits hypogastric nerve stimulation and this could counteract any antagonism of the effects of clonidine at the presynaptic alpha-adrenoceptor. The results demonstrate the uptake blocking properties of mianserin and its antagonism at both pre- and postsynaptic alpha-adrenoceptors."}
{"id": "PMID:29762", "title": "Studies on renal dopamine receptors with a new agonist.", "content": "SK & F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) is a new dopamine receptor agonist which selectively increased renal blood flow when administered i.v. to dogs at cumulative doses of 3.3-1333 microgram/kg. Consistent changes in arterial blood pressure heart rate and cardiac output were not observed. The renal response, which was mediated locally in the kidney, was not antagonized by adequate blocking doses of atropine, propranolol, metiamide and/or mepyramine nor by reserpinization or treatment with indomethacin. It was inhibited, however, by the selective peripheral dopamine receptor antagonist, bulbocapnine. Perhaps as a result of its action on renal blood flow, SK & F 38393 produced a diuresis in normally hydrated rats which was characterized by an increased excretion of sodium, potassium and chloride and a increased urinary pH. Compounds of this type may be useful in better defining dopaminergic receptors and in the treatment of disease states where renal ischemia is present.", "contents": "Studies on renal dopamine receptors with a new agonist. SK & F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) is a new dopamine receptor agonist which selectively increased renal blood flow when administered i.v. to dogs at cumulative doses of 3.3-1333 microgram/kg. Consistent changes in arterial blood pressure heart rate and cardiac output were not observed. The renal response, which was mediated locally in the kidney, was not antagonized by adequate blocking doses of atropine, propranolol, metiamide and/or mepyramine nor by reserpinization or treatment with indomethacin. It was inhibited, however, by the selective peripheral dopamine receptor antagonist, bulbocapnine. Perhaps as a result of its action on renal blood flow, SK & F 38393 produced a diuresis in normally hydrated rats which was characterized by an increased excretion of sodium, potassium and chloride and a increased urinary pH. Compounds of this type may be useful in better defining dopaminergic receptors and in the treatment of disease states where renal ischemia is present."}
{"id": "PMID:29763", "title": "An interaction of histamine H2-receptor antagonists with the noradrenergic system in rat brain.", "content": "Intraventricular administration of 50 microgram of burimamide or 250 microgram of either metiamide or cimetidine decreased the NA concentration in rat hypothalamus by nearly 30%. Cimetidine did not significantly influence either DA or DOPAC levels in striatum. Cimetidine and metiamide significantly potentiated locomotor activity of tranylcypromine-treated rats and this effect was antagonized by phentolamine. It is concluded that the three histamine H2-receptor antagonists released NA in rat brain.", "contents": "An interaction of histamine H2-receptor antagonists with the noradrenergic system in rat brain. Intraventricular administration of 50 microgram of burimamide or 250 microgram of either metiamide or cimetidine decreased the NA concentration in rat hypothalamus by nearly 30%. Cimetidine did not significantly influence either DA or DOPAC levels in striatum. Cimetidine and metiamide significantly potentiated locomotor activity of tranylcypromine-treated rats and this effect was antagonized by phentolamine. It is concluded that the three histamine H2-receptor antagonists released NA in rat brain."}
{"id": "PMID:29764", "title": "Differential blockade of bicuculline convulsions by neuroleptics.", "content": "Haloperidol, pimozide, sulpiride and metoclopramide blocked bicuculline-induced convulsions in mice. Chlorpromazine and thioridazine exhibited this effect at low doses whereas at higher doses (e.g. 1 mg/kg i.p. chlorpromazine) this activity was no longer apparent. A dose of phenoxybenzamine which was inactive alone (7.5 mg/kg i.p.) completely blocked the anti-bicuculline effect of sulpiride and antagonized that of haloperidol. These data are interpreted as indicating that intact noradrenergic systems are necessary for the anti-bicuculline effect of the neuroleptics.", "contents": "Differential blockade of bicuculline convulsions by neuroleptics. Haloperidol, pimozide, sulpiride and metoclopramide blocked bicuculline-induced convulsions in mice. Chlorpromazine and thioridazine exhibited this effect at low doses whereas at higher doses (e.g. 1 mg/kg i.p. chlorpromazine) this activity was no longer apparent. A dose of phenoxybenzamine which was inactive alone (7.5 mg/kg i.p.) completely blocked the anti-bicuculline effect of sulpiride and antagonized that of haloperidol. These data are interpreted as indicating that intact noradrenergic systems are necessary for the anti-bicuculline effect of the neuroleptics."}
{"id": "PMID:29766", "title": "Neuropharmacological studies on the nigro-striatal and raphe-striatal system in the rat.", "content": "The responses of single neostriatal neurones to substantia nigra (SN) and dorsal raphe nucleus (DRN) stimulation and iontophoretic administration of several drugs were studied in urethane-anaesthetised rats. Stimulation of the SN-evoked excitation followed by inhibition in striatal neurones. In some cells only inhibition of firing was evoked indicating that there may be separate nigrostriatal inhibitory and excitatory pathways. DRN stimulation evoked mainly inhibition of striatal cell firing. The activity of most neurones responding to SN and DRN stimulation was depressed by iontophoretically administered dopamine, 5-hydroxytryptamine and GABA and increased by acetylcholine. Studies with antagonist revealed that alpha-flupenthixol reduced responses to dopamine and 5-hydroxytryptamine and inhibition evoked by SN and DRN stimulation. Bicuculline methochloride only reduced responses to GABA. Methysergide selectively reduced responses to 5-hydroxytryptamine and also reduced DRN-but not SN-evoked inhibition. It was concluded that the SN-evoked inhibition was probably mediated by dopamine and DRN-evoked inhibition by 5-hydroxytryptamine.", "contents": "Neuropharmacological studies on the nigro-striatal and raphe-striatal system in the rat. The responses of single neostriatal neurones to substantia nigra (SN) and dorsal raphe nucleus (DRN) stimulation and iontophoretic administration of several drugs were studied in urethane-anaesthetised rats. Stimulation of the SN-evoked excitation followed by inhibition in striatal neurones. In some cells only inhibition of firing was evoked indicating that there may be separate nigrostriatal inhibitory and excitatory pathways. DRN stimulation evoked mainly inhibition of striatal cell firing. The activity of most neurones responding to SN and DRN stimulation was depressed by iontophoretically administered dopamine, 5-hydroxytryptamine and GABA and increased by acetylcholine. Studies with antagonist revealed that alpha-flupenthixol reduced responses to dopamine and 5-hydroxytryptamine and inhibition evoked by SN and DRN stimulation. Bicuculline methochloride only reduced responses to GABA. Methysergide selectively reduced responses to 5-hydroxytryptamine and also reduced DRN-but not SN-evoked inhibition. It was concluded that the SN-evoked inhibition was probably mediated by dopamine and DRN-evoked inhibition by 5-hydroxytryptamine."}
{"id": "PMID:29768", "title": "Sensitivity of lateral cerebellar nucleus to macular stimulation in the rabbit.", "content": "Experiments were performed in decerebrate rabbits to determine the sensitivity of the lateral cerebellar nucleus (LCN) to macular stimulation. Twenty-three percent of the neurons recorded extracellularly in the LCN showed steady changes in their discharge rate during 20 degrees tilt in both directions of the medial plane. Most of these neurons exhibited an alpha- and beta-type of response. A few gamma-types, but no delta-types were observed. The units sensitive to tilt were restricted to the caudal half of the LCN. Some of these positionally sensitive neurons responded monosynaptically to ipsilateral labyrinthine stimulation, but many received a polysynaptic input. These units could be activated antidromically by stimulation of the oculomotor nucleus but at a very high intensity suggesting current spread to the nearby brachium conjunctivum fibers. These results exclude a role of the LCN in the disynaptic otolith-ocular reflex.", "contents": "Sensitivity of lateral cerebellar nucleus to macular stimulation in the rabbit. Experiments were performed in decerebrate rabbits to determine the sensitivity of the lateral cerebellar nucleus (LCN) to macular stimulation. Twenty-three percent of the neurons recorded extracellularly in the LCN showed steady changes in their discharge rate during 20 degrees tilt in both directions of the medial plane. Most of these neurons exhibited an alpha- and beta-type of response. A few gamma-types, but no delta-types were observed. The units sensitive to tilt were restricted to the caudal half of the LCN. Some of these positionally sensitive neurons responded monosynaptically to ipsilateral labyrinthine stimulation, but many received a polysynaptic input. These units could be activated antidromically by stimulation of the oculomotor nucleus but at a very high intensity suggesting current spread to the nearby brachium conjunctivum fibers. These results exclude a role of the LCN in the disynaptic otolith-ocular reflex."}
{"id": "PMID:29769", "title": "Ultrastructural differences in mitochondria of skeletal muscle in the prerigor and rigor states.", "content": "Loss of cristae and matrix occur in the mitochondria of skeletal muscles prior to any observable changes in myofibrillar proteins during the development of rigor mortis. Care must be observed because ultrastructural changes in mitochondria in some studies may be attributed to a specific trauma, whereas the changes may be due to the lower pH in postmortem muscle.", "contents": "Ultrastructural differences in mitochondria of skeletal muscle in the prerigor and rigor states. Loss of cristae and matrix occur in the mitochondria of skeletal muscles prior to any observable changes in myofibrillar proteins during the development of rigor mortis. Care must be observed because ultrastructural changes in mitochondria in some studies may be attributed to a specific trauma, whereas the changes may be due to the lower pH in postmortem muscle."}
{"id": "PMID:29770", "title": "31P-NMR study on nucleotides and intracellular pH of hereditary spherocytes.", "content": "As determined by 31p-NMR spectroscopy, intracellular pH of hereditary spherocytes was lower (pH 6.7-6.9) than that of normal red cells. The level of adenosine diphosphate in hereditary spherocytes was found to be persistently high. The metabolism of nucleotides and other phosphoryl compounds in human red blood cells have been studied in detail by 31p-MNR spectroscopy. However, to our knowledge, there seems to be no report describing the result of 31p-NMR spectroscopy on red blood cells from hereditary spherocytosis.", "contents": "31P-NMR study on nucleotides and intracellular pH of hereditary spherocytes. As determined by 31p-NMR spectroscopy, intracellular pH of hereditary spherocytes was lower (pH 6.7-6.9) than that of normal red cells. The level of adenosine diphosphate in hereditary spherocytes was found to be persistently high. The metabolism of nucleotides and other phosphoryl compounds in human red blood cells have been studied in detail by 31p-MNR spectroscopy. However, to our knowledge, there seems to be no report describing the result of 31p-NMR spectroscopy on red blood cells from hereditary spherocytosis."}
{"id": "PMID:29771", "title": "Effect of adrenaline and adrenergic active drugs on growth hormone secretion in immature cockerels.", "content": "In immature cockerels adrenaline administration lowered the levels of plasma growth hormone. Both alpha and beta adrenergic receptor agonists also depressed the circulating growth hormone levels. In the presence of beta blockade, the suppressive effect of adrenaline on growth hormone secretion was not observed.", "contents": "Effect of adrenaline and adrenergic active drugs on growth hormone secretion in immature cockerels. In immature cockerels adrenaline administration lowered the levels of plasma growth hormone. Both alpha and beta adrenergic receptor agonists also depressed the circulating growth hormone levels. In the presence of beta blockade, the suppressive effect of adrenaline on growth hormone secretion was not observed."}
{"id": "PMID:29775", "title": "Behavior therapy in a family context: treating elective mutism.", "content": "This paper discusses the necessity of using both behavioral and family approaches in combination, while working with electively mute children. The symptom and its significance within the family system is presented along with a rationale for avoiding the pitfalls of individual approaches with such children. A case history outlining specific behavioral techniques is described in detail with an exploration of the use of reinforcement theory, counter-conditioning, and successive approximations in bringing about change in electively mute children. The need for bringing about changes within the family system so as to maintain the changes that have occurred through use of the behavior techniques is discussed and presented as crucial to the treatment process. The paper takes the position that either approach, by itself, will not be effective in helping electively mute children but that the treatment of choice is a combination of therapeutic techniques.", "contents": "Behavior therapy in a family context: treating elective mutism. This paper discusses the necessity of using both behavioral and family approaches in combination, while working with electively mute children. The symptom and its significance within the family system is presented along with a rationale for avoiding the pitfalls of individual approaches with such children. A case history outlining specific behavioral techniques is described in detail with an exploration of the use of reinforcement theory, counter-conditioning, and successive approximations in bringing about change in electively mute children. The need for bringing about changes within the family system so as to maintain the changes that have occurred through use of the behavior techniques is discussed and presented as crucial to the treatment process. The paper takes the position that either approach, by itself, will not be effective in helping electively mute children but that the treatment of choice is a combination of therapeutic techniques."}
{"id": "PMID:29777", "title": "[Influence of adrenergic-blocking agents on the pain-alleviating effect of narcotic analgesics].", "content": "The action of adrenoblocking agents on the dynamics of the pain allaying effect of narcotic analgesics, measured by the magnitude of the pain reaction threshold after irritation of the tail skin with electric current was studies in tests on mice. The beta-adreno-blocking agent (anaprillin or inderal) was found to significantly potentiate and to lengthen the action of morphine, and so did, to a lesser degree, promedol (trimeperedin) and phentanyl, while the alpha-adrenoblocking agent (phentolamine) weakened the analgesic effects of morphine and promedol, without having any essential influence on the effect of phentanyl. Phentolamine does not eliminate the potentiating effect of anapraline on the analgesic action of morphine but is capable to lessen it.", "contents": "[Influence of adrenergic-blocking agents on the pain-alleviating effect of narcotic analgesics]. The action of adrenoblocking agents on the dynamics of the pain allaying effect of narcotic analgesics, measured by the magnitude of the pain reaction threshold after irritation of the tail skin with electric current was studies in tests on mice. The beta-adreno-blocking agent (anaprillin or inderal) was found to significantly potentiate and to lengthen the action of morphine, and so did, to a lesser degree, promedol (trimeperedin) and phentanyl, while the alpha-adrenoblocking agent (phentolamine) weakened the analgesic effects of morphine and promedol, without having any essential influence on the effect of phentanyl. Phentolamine does not eliminate the potentiating effect of anapraline on the analgesic action of morphine but is capable to lessen it."}
{"id": "PMID:29791", "title": "Channels in epithelial cell membranes and junctions.", "content": "Epithelia may be classified as \"tight\" or \"leaky,\" depending on whether there is a significant pathway for transepithelial ion permeation via the junctions and bypassing the cells. The resistance of this paracellular channel may depend partly on structures visible in the electron microscope, partly on wall charge. Permeability determinations in the leaky junctions of gallbladder epithelium, using many different organic cations, suggest that the critical barriers barriers to ion permeation are 5--8 A in radius and bind cations by up to four strongly proton-accepting oxygens. The apical cell membrane of tight epithelia contains a Na+-selective channel that is blocked by amiloride and Ca2+, subject to negative feedback control by the Na+ pump in the basolateral membrane, and somehow promoted by aldosterone. To determine the permeabilities of these two channels (the junctional channel of leaky epithelia, and the Na+ channel of tight epithelia) to water and nonelectrolytes remains a major unsolved problem.", "contents": "Channels in epithelial cell membranes and junctions. Epithelia may be classified as \"tight\" or \"leaky,\" depending on whether there is a significant pathway for transepithelial ion permeation via the junctions and bypassing the cells. The resistance of this paracellular channel may depend partly on structures visible in the electron microscope, partly on wall charge. Permeability determinations in the leaky junctions of gallbladder epithelium, using many different organic cations, suggest that the critical barriers barriers to ion permeation are 5--8 A in radius and bind cations by up to four strongly proton-accepting oxygens. The apical cell membrane of tight epithelia contains a Na+-selective channel that is blocked by amiloride and Ca2+, subject to negative feedback control by the Na+ pump in the basolateral membrane, and somehow promoted by aldosterone. To determine the permeabilities of these two channels (the junctional channel of leaky epithelia, and the Na+ channel of tight epithelia) to water and nonelectrolytes remains a major unsolved problem."}
{"id": "PMID:29792", "title": "Effects of monitoring high-risk pregnancies and intrapartum FHR monitoring on perinates.", "content": "A protocol of chronic antepartum surveillance was initiated at the University of Illinois hospitals in 1973 to assess the impact on perinatal mortality. At the same time, a policy of unselected fetal heart rate (FHR) monitoring was initiated to judge the effect on the intrapartum stillbirth rate. The impact of both programs played a significant role in the decline of perinatal mortality rates for infants weighing more than 1 500 g, from 21.1/1 000 births in 1970--1971 to 14.4/1 000 births in the monitored years 1973 and 1974 (p less than 0.02).", "contents": "Effects of monitoring high-risk pregnancies and intrapartum FHR monitoring on perinates. A protocol of chronic antepartum surveillance was initiated at the University of Illinois hospitals in 1973 to assess the impact on perinatal mortality. At the same time, a policy of unselected fetal heart rate (FHR) monitoring was initiated to judge the effect on the intrapartum stillbirth rate. The impact of both programs played a significant role in the decline of perinatal mortality rates for infants weighing more than 1 500 g, from 21.1/1 000 births in 1970--1971 to 14.4/1 000 births in the monitored years 1973 and 1974 (p less than 0.02)."}
{"id": "PMID:29793", "title": "Obstetric aspects of adolescent pregnancy and delivery.", "content": "An analysis of 31 years of adolescent pregnancies and deliveries at Novi Sad Medical Facility is presented. Obstetric complications are discussed. The psychological impact of adolescent pregnancy is examined.", "contents": "Obstetric aspects of adolescent pregnancy and delivery. An analysis of 31 years of adolescent pregnancies and deliveries at Novi Sad Medical Facility is presented. Obstetric complications are discussed. The psychological impact of adolescent pregnancy is examined."}
{"id": "PMID:29794", "title": "Carcinoma in situ cervicis uteri: diagnosis, treatment and prognosis.", "content": "A total of 252 patients with carcinoma in situ colli uteri were treated at the Women's Clinic at Turku University between 1964 and 1971. Seventy-seven percent of the patients came to the clinic for treatment after they had participated in a mass screening program (cytodiagnosis, colposcopy). Extrafascial hysterectomy was performed most often on women in the older age groups, while most of the younger patients were treated by conization. Patients were followed up for a minimum of 5 years. There was a 1.0% recurrence of invasive carcinoma and a 4.0% recurrence of noninvasive carcinoma. All invasive recurrences occurred after hysterectomy. None of the patients died from complications of carcinoma.", "contents": "Carcinoma in situ cervicis uteri: diagnosis, treatment and prognosis. A total of 252 patients with carcinoma in situ colli uteri were treated at the Women's Clinic at Turku University between 1964 and 1971. Seventy-seven percent of the patients came to the clinic for treatment after they had participated in a mass screening program (cytodiagnosis, colposcopy). Extrafascial hysterectomy was performed most often on women in the older age groups, while most of the younger patients were treated by conization. Patients were followed up for a minimum of 5 years. There was a 1.0% recurrence of invasive carcinoma and a 4.0% recurrence of noninvasive carcinoma. All invasive recurrences occurred after hysterectomy. None of the patients died from complications of carcinoma."}
{"id": "PMID:29795", "title": "Birth interval study in a culturally stable urban population.", "content": "Five hundred women were interviewed within 2 days of delivery to examine indigenous birth spacing among the urban and rural population of Ife township. The crude birth interval was between 30 and 40 months due mainly to cultural attitudes towards lactation and sexual abstinence. The women studied possessed considerable knowledge of Western contraceptive methods, but they rejected them. The possible cause of this rejection is examined and solutions to the problem are suggested.", "contents": "Birth interval study in a culturally stable urban population. Five hundred women were interviewed within 2 days of delivery to examine indigenous birth spacing among the urban and rural population of Ife township. The crude birth interval was between 30 and 40 months due mainly to cultural attitudes towards lactation and sexual abstinence. The women studied possessed considerable knowledge of Western contraceptive methods, but they rejected them. The possible cause of this rejection is examined and solutions to the problem are suggested."}
{"id": "PMID:29796", "title": "Metronidazole treatment in pregnancy.", "content": "Vaginal trichomoniasis was treated with standard courses of oral metronidazole in 597 pregnant women. In 283 other pregnant women, the infection remained untreated. The incidences of low-birth-weight infants, stillbirths and congenital abnormalities were not affected by metronidazole treatment of trichomoniasis in pregnancy.", "contents": "Metronidazole treatment in pregnancy. Vaginal trichomoniasis was treated with standard courses of oral metronidazole in 597 pregnant women. In 283 other pregnant women, the infection remained untreated. The incidences of low-birth-weight infants, stillbirths and congenital abnormalities were not affected by metronidazole treatment of trichomoniasis in pregnancy."}
{"id": "PMID:29797", "title": "Evaluation of 496 menstrual regulation and abortion patients in Calcutta.", "content": "From March to December 1975, 496 patients were studied to compare the safety and effectiveness of menstrual regulation (MR) performed with a Karman hand syringe and first trimester abortion performed with an electric vacuum aspirator. All procedures were done on an outpatient basis. The complication rate for the MR patients was significantly lower than that for the other first trimester abortion patients. Study results indicate that MR with the Karman syringe is a safer, simpler and less costly procedure than first trimester abortion with the electric vacuum aspirator. Further research and study are necessary to determine the effect of the initial and repeat MR procedures on women's menstrual patterns and future pregnancies, including any subsequent prematurity, stillbirths and Rh immunization.", "contents": "Evaluation of 496 menstrual regulation and abortion patients in Calcutta. From March to December 1975, 496 patients were studied to compare the safety and effectiveness of menstrual regulation (MR) performed with a Karman hand syringe and first trimester abortion performed with an electric vacuum aspirator. All procedures were done on an outpatient basis. The complication rate for the MR patients was significantly lower than that for the other first trimester abortion patients. Study results indicate that MR with the Karman syringe is a safer, simpler and less costly procedure than first trimester abortion with the electric vacuum aspirator. Further research and study are necessary to determine the effect of the initial and repeat MR procedures on women's menstrual patterns and future pregnancies, including any subsequent prematurity, stillbirths and Rh immunization."}
{"id": "PMID:29798", "title": "Variable range directional doppler and abdominal ECG for FHR monitoring.", "content": "Antepartum nonstress fetal heart rate (FHR) monitoring may become a valuable screening tool for all pregnancies. Two methods proposed for an antepartum FHR monitor are examined: abdominal electrocardiogram (AECG) and variable range directional Doppler (RDD). A good quality (detailed, clearcut baseline) RDD FHR record was obtained in 74/75 (99%) examinations, and a good quality AECG record was obtained i31/75 (41%). Each patient was monitored in the supine, lateral and sitting positions. Considering all positions, 76% of the RDD records and 19% of the AECG records were good. The RDD system was efficacious for routine, clinical antepartum FHR monitoring, but the performance of the AECG was too limited for this purpose.", "contents": "Variable range directional doppler and abdominal ECG for FHR monitoring. Antepartum nonstress fetal heart rate (FHR) monitoring may become a valuable screening tool for all pregnancies. Two methods proposed for an antepartum FHR monitor are examined: abdominal electrocardiogram (AECG) and variable range directional Doppler (RDD). A good quality (detailed, clearcut baseline) RDD FHR record was obtained in 74/75 (99%) examinations, and a good quality AECG record was obtained i31/75 (41%). Each patient was monitored in the supine, lateral and sitting positions. Considering all positions, 76% of the RDD records and 19% of the AECG records were good. The RDD system was efficacious for routine, clinical antepartum FHR monitoring, but the performance of the AECG was too limited for this purpose."}
{"id": "PMID:29799", "title": "Estrogens in food: the almond mystery.", "content": "Studies were made of 36 different nuts, grains, fruits and vegetables commonly used as human foods; each of these was fed to a group of ovariectomized rats for 10 days as a sole diet. The estrogenic activities of the foods were estimated by comparing the uterine weights, uterine fluid volumes and the vaginal cornification indices of each group of rats with those of groups fed other foods. Almonds, cashew nuts, peanuts, oats, corn, wheat and apples all showed estrogenic activity. The original sample of almonds showed the greatest estrogenic activity (p less than 0.01) which was confirmed by repetition of the experiment (p less than 0.01), but subsequent studies of other samples of almonds showed no estrogenic activity. Possible reasons for the disparity of the results with different lots of almonds are discussed.", "contents": "Estrogens in food: the almond mystery. Studies were made of 36 different nuts, grains, fruits and vegetables commonly used as human foods; each of these was fed to a group of ovariectomized rats for 10 days as a sole diet. The estrogenic activities of the foods were estimated by comparing the uterine weights, uterine fluid volumes and the vaginal cornification indices of each group of rats with those of groups fed other foods. Almonds, cashew nuts, peanuts, oats, corn, wheat and apples all showed estrogenic activity. The original sample of almonds showed the greatest estrogenic activity (p less than 0.01) which was confirmed by repetition of the experiment (p less than 0.01), but subsequent studies of other samples of almonds showed no estrogenic activity. Possible reasons for the disparity of the results with different lots of almonds are discussed."}
{"id": "PMID:29800", "title": "Asherman's syndrome--a self-limiting disease?", "content": "Intrauterine adhesions (Asherman's syndrome) may follow curettage in a recently pregnant uterus. Treatment consisting of dilatation and curettage and possibly the insertion of an intrauterine device usually is started early. The success rate is high. Very few cases of spontaneous recurring menstruation have been reported, and none of them have been based on hysterosalpingographic evidence of adhesions. The pregnancy outcome is generally poor in those cases of assumed spontaneous resolution. We present a case of spontaneous restitution of a functional uterine cavity and normal menstruation following Asherman's syndrome. Subsequent pregnancy was uneventful. A short review of the literature is presented, and the possible self-limiting character of the disease is discussed.", "contents": "Asherman's syndrome--a self-limiting disease? Intrauterine adhesions (Asherman's syndrome) may follow curettage in a recently pregnant uterus. Treatment consisting of dilatation and curettage and possibly the insertion of an intrauterine device usually is started early. The success rate is high. Very few cases of spontaneous recurring menstruation have been reported, and none of them have been based on hysterosalpingographic evidence of adhesions. The pregnancy outcome is generally poor in those cases of assumed spontaneous resolution. We present a case of spontaneous restitution of a functional uterine cavity and normal menstruation following Asherman's syndrome. Subsequent pregnancy was uneventful. A short review of the literature is presented, and the possible self-limiting character of the disease is discussed."}
{"id": "PMID:29801", "title": "Intrapartum maternal and fetal monitoring: the obstetric intensive care unit.", "content": "The Obstetric Intensive Care Unit (OBICU) at Bellevue Hospital in New York City has adapted intensive care and coronary care models to the care of patients in labor. During the past 3 years, 519 of the most serious of 2 250 high-risk obstetric patients treated at the hospital were monitored in the OBICU. There were two maternal and six perinatal deaths. The perinatal mortality rate of the very high risk population of the OBICU was 11.6/1 000, compared to 14.7/1 000 for all deliveries performed at the hospital. Our findings indicate that the OBICU system provides the ideal mechanism for the rapid and continuous control of symptoms in very high risk gravidas which is essential for stabilizing the patient, both for prompt delivery and for optimal maternal and fetal survival.", "contents": "Intrapartum maternal and fetal monitoring: the obstetric intensive care unit. The Obstetric Intensive Care Unit (OBICU) at Bellevue Hospital in New York City has adapted intensive care and coronary care models to the care of patients in labor. During the past 3 years, 519 of the most serious of 2 250 high-risk obstetric patients treated at the hospital were monitored in the OBICU. There were two maternal and six perinatal deaths. The perinatal mortality rate of the very high risk population of the OBICU was 11.6/1 000, compared to 14.7/1 000 for all deliveries performed at the hospital. Our findings indicate that the OBICU system provides the ideal mechanism for the rapid and continuous control of symptoms in very high risk gravidas which is essential for stabilizing the patient, both for prompt delivery and for optimal maternal and fetal survival."}
{"id": "PMID:29802", "title": "Inducing labor with oral prostaglandin E2 in Khartoum hospital.", "content": "Prostagland-n E2 (PGE2) was administered orally to 109 patients to induce labor. Sixty-five of these patients had an amniotomy prior to PGE2 administration. PGE2 was administered to the remaining. 44, who subsequently underwent amniotomy only after their cervices had reached approximately 6 cm dilation. Labor was successfully induced in 95 patients, but its duration was shorter when amniotomy was immediatedly followed by PGE2 administration. Failed cases were successfully managed with amniotomy and oxytocin infusion. Maternal side effects were minimal. No fetal complications occurred.", "contents": "Inducing labor with oral prostaglandin E2 in Khartoum hospital. Prostagland-n E2 (PGE2) was administered orally to 109 patients to induce labor. Sixty-five of these patients had an amniotomy prior to PGE2 administration. PGE2 was administered to the remaining. 44, who subsequently underwent amniotomy only after their cervices had reached approximately 6 cm dilation. Labor was successfully induced in 95 patients, but its duration was shorter when amniotomy was immediatedly followed by PGE2 administration. Failed cases were successfully managed with amniotomy and oxytocin infusion. Maternal side effects were minimal. No fetal complications occurred."}
{"id": "PMID:29803", "title": "Burst abdomen following cesarean section.", "content": "Fifty-one cases of burst abdomen occurred following 1 988 cesarean sections performed at the University of Nigeria Teaching Hospital over a 5-year period. The incidence of this occurrence was 2.6% (2.3% if all laparotomies in both obstetrics and gynecology are combined). The risk was three times as great for \"unbooked\" patients, who were first seen in labor. Possible etiologic factors and preventive measures are discussed.", "contents": "Burst abdomen following cesarean section. Fifty-one cases of burst abdomen occurred following 1 988 cesarean sections performed at the University of Nigeria Teaching Hospital over a 5-year period. The incidence of this occurrence was 2.6% (2.3% if all laparotomies in both obstetrics and gynecology are combined). The risk was three times as great for \"unbooked\" patients, who were first seen in labor. Possible etiologic factors and preventive measures are discussed."}
{"id": "PMID:29804", "title": "Plasma estradiol as a predictor of preterm labor.", "content": "Studies have shown a rapid rise of plasma estradiol-17beta in the maternal circulation before the occurrence of preterm labor. We have attempted to perform a linear regression analysis of the data from normal pregnancies and to set up a 95% upper prediction limit for the normal range of the estradiol level for each week of gestation. The prediction limits were reasonably good, with only five (13%) false negatives. False negatives tend to occur only in late pregnancy.", "contents": "Plasma estradiol as a predictor of preterm labor. Studies have shown a rapid rise of plasma estradiol-17beta in the maternal circulation before the occurrence of preterm labor. We have attempted to perform a linear regression analysis of the data from normal pregnancies and to set up a 95% upper prediction limit for the normal range of the estradiol level for each week of gestation. The prediction limits were reasonably good, with only five (13%) false negatives. False negatives tend to occur only in late pregnancy."}
{"id": "PMID:29806", "title": "The role of methylergonovine maleate in augmenting extraamniotic saline for midtrimester abortion.", "content": "This study was conducted in Bombay, India, to evaluate the role of oral methylergonovine maleate (Methergine, Sandoz Pharmaceuticals, East Hanover, N.J., USA) in augmenting the effect of intermittent extraamniotic instillation of 20% saline for midtrimester abortion in 200 patients. Methylergonovine maleate (MEM) administration was randomly allocated to half the study subjects. All the study procedures were performed by a single operator, and to minimize evaluator bias, another physician evaluated all the study patients after abortion. This study showed that a statistically significant higher percentage of patients in the MEM treated group aborted within 24 hours. At 36 and 48 hours, the differences were not statistically significant, although the cumulative abortion rates were higher for subjects who received the drug than for those who did not. The incidence of incomplete abortions was lower for those treated with MEM than for those not treated with the drug, but the difference was not statistically significant. The rates of complications and side effects were similar for both study groups.", "contents": "The role of methylergonovine maleate in augmenting extraamniotic saline for midtrimester abortion. This study was conducted in Bombay, India, to evaluate the role of oral methylergonovine maleate (Methergine, Sandoz Pharmaceuticals, East Hanover, N.J., USA) in augmenting the effect of intermittent extraamniotic instillation of 20% saline for midtrimester abortion in 200 patients. Methylergonovine maleate (MEM) administration was randomly allocated to half the study subjects. All the study procedures were performed by a single operator, and to minimize evaluator bias, another physician evaluated all the study patients after abortion. This study showed that a statistically significant higher percentage of patients in the MEM treated group aborted within 24 hours. At 36 and 48 hours, the differences were not statistically significant, although the cumulative abortion rates were higher for subjects who received the drug than for those who did not. The incidence of incomplete abortions was lower for those treated with MEM than for those not treated with the drug, but the difference was not statistically significant. The rates of complications and side effects were similar for both study groups."}
{"id": "PMID:29807", "title": "Atypical cervical cytology and colposcopic directed biopsy.", "content": "A cervical cytologic diagnosis of inflammatory stypia was made in 319 patients during a 42-month period. Two hundred twenty-five of those patients underwent colposcopy, and biopsy was performed in 155 patients. Mild to severe dysplasia was diagnosed in 115 patients, for a 36% prevalence of cervical intraepithelial neoplasia.", "contents": "Atypical cervical cytology and colposcopic directed biopsy. A cervical cytologic diagnosis of inflammatory stypia was made in 319 patients during a 42-month period. Two hundred twenty-five of those patients underwent colposcopy, and biopsy was performed in 155 patients. Mild to severe dysplasia was diagnosed in 115 patients, for a 36% prevalence of cervical intraepithelial neoplasia."}
{"id": "PMID:29808", "title": "The pure gonadal dysgenesis syndrome.", "content": "Two cases of gonadal dysgenesis in phenotypic females associated with different chromosomal patterns are discussed. Both patients presented with primary amenorrhea and were characterized by tall stature and underdeveloped secondary sex characteristics and external and internal reproductive organs. The karyotype of the first patient was 46,XX with a satellite on chromosome 17. The second patient had a normal female chromosome composition (46,XX) with a past history of mumps. Laparoscopic bilateral gonadal biopsies in both patients revealed fibrous tissue without any primordial follicles. This report emphasizes the pathogenesis, clinical significance, diagnosis and management of gonadal dysgenesis.", "contents": "The pure gonadal dysgenesis syndrome. Two cases of gonadal dysgenesis in phenotypic females associated with different chromosomal patterns are discussed. Both patients presented with primary amenorrhea and were characterized by tall stature and underdeveloped secondary sex characteristics and external and internal reproductive organs. The karyotype of the first patient was 46,XX with a satellite on chromosome 17. The second patient had a normal female chromosome composition (46,XX) with a past history of mumps. Laparoscopic bilateral gonadal biopsies in both patients revealed fibrous tissue without any primordial follicles. This report emphasizes the pathogenesis, clinical significance, diagnosis and management of gonadal dysgenesis."}
{"id": "PMID:29809", "title": "Oral contraceptive pills and clinical otosclerosis.", "content": "Clinical otosclerosis is a familial disease which is more frequent among women in their reproductive years. The condition usuallly is aggravated by pregnancy. Endocrinologic variables may influence the time of onset and the course of the disease. It is suspected that oral contraceptives (OCs) might stimulate the onset of the disease. Six hundred nulliparous women between the ages of 16 and 30, who used a variety of OCs for 12-36 months, were examined. The hearing of these women was thoroughly investigated. The first audiometric examination of the 600 women revealed three cases (0.5%) of clinical otosclerosis. This incidence is equal to that of the population as a whole, but lower than the  incidence found in previously parous women. Audiometric examinations were normal in the remaining 597 women, and repeated examinations revealed no new cases of clinical otosclerosis, despite continuous OC use.", "contents": "Oral contraceptive pills and clinical otosclerosis. Clinical otosclerosis is a familial disease which is more frequent among women in their reproductive years. The condition usuallly is aggravated by pregnancy. Endocrinologic variables may influence the time of onset and the course of the disease. It is suspected that oral contraceptives (OCs) might stimulate the onset of the disease. Six hundred nulliparous women between the ages of 16 and 30, who used a variety of OCs for 12-36 months, were examined. The hearing of these women was thoroughly investigated. The first audiometric examination of the 600 women revealed three cases (0.5%) of clinical otosclerosis. This incidence is equal to that of the population as a whole, but lower than the  incidence found in previously parous women. Audiometric examinations were normal in the remaining 597 women, and repeated examinations revealed no new cases of clinical otosclerosis, despite continuous OC use."}
{"id": "PMID:29810", "title": "Diagnostic laparoscopy.", "content": "Six hundred fifty-eight laparoscopies were performed at St. Luke's Hospital, Kansas City, Missouri, USA, between March 1, 1976 and February 28, 1977. One hundred sixty-eight (25.5%) were performed for diagnostic purposes. A review of the preoperative diagnoses and the laparoscopic findings demonstrates the value of laparoscopy as a diagnostic procedure.", "contents": "Diagnostic laparoscopy. Six hundred fifty-eight laparoscopies were performed at St. Luke's Hospital, Kansas City, Missouri, USA, between March 1, 1976 and February 28, 1977. One hundred sixty-eight (25.5%) were performed for diagnostic purposes. A review of the preoperative diagnoses and the laparoscopic findings demonstrates the value of laparoscopy as a diagnostic procedure."}
{"id": "PMID:29811", "title": "Endometriosis presenting as acute appendicitis.", "content": "A rare case of endometriosis presenting as acute appendicitis is reported. Appendectomy was performed with excellent results.", "contents": "Endometriosis presenting as acute appendicitis. A rare case of endometriosis presenting as acute appendicitis is reported. Appendectomy was performed with excellent results."}
{"id": "PMID:29812", "title": "Urinary electrolyte profiles after amiloride, hydrochlorthiazide and the combination.", "content": "Acute effects of amiloride (5 mg) (A), hydrochlorthiazide (50 mg) (H) and the combination (50 + 5 mg) (HA) on urinary electrolyte excretion and pH of ten healthy volunteers--taking placebo five times and twice randomly A and HA and once H--were studied during one day. Amiloride showed a natriuretic effect, which in combination was additive to that of hydrochlorthiazide, but the excretion of water did not increase significantly after A. The urinary excretion of potassium decreased with amiloride below normal levels and was at the level of placebo after the combination (HA). There was a striking linear correlation between urinary sodium and potassium with all the drugs, although showing with A a higher potassium retention during high sodium excretion. Urinary pH rose after A and HA during the first 8 hours, but this effect was not seen, however, after H. No significant differences in the effect of the two brands of A (Medamor and Puritrid) on the urinary electrolyte excretion and pH, nor in those of the two brands of HA (Moduretic and Amitrid) were found. Similarly, the plasma concentrations of hydrochlorthiazide, determined gas chromatographically, were equal after Moduretic and Amitrid tablets. The systemic availability of H was faster in the combination of HA than alone. In the AUC value of H, however, there was no significant difference between HA and H tablets.", "contents": "Urinary electrolyte profiles after amiloride, hydrochlorthiazide and the combination. Acute effects of amiloride (5 mg) (A), hydrochlorthiazide (50 mg) (H) and the combination (50 + 5 mg) (HA) on urinary electrolyte excretion and pH of ten healthy volunteers--taking placebo five times and twice randomly A and HA and once H--were studied during one day. Amiloride showed a natriuretic effect, which in combination was additive to that of hydrochlorthiazide, but the excretion of water did not increase significantly after A. The urinary excretion of potassium decreased with amiloride below normal levels and was at the level of placebo after the combination (HA). There was a striking linear correlation between urinary sodium and potassium with all the drugs, although showing with A a higher potassium retention during high sodium excretion. Urinary pH rose after A and HA during the first 8 hours, but this effect was not seen, however, after H. No significant differences in the effect of the two brands of A (Medamor and Puritrid) on the urinary electrolyte excretion and pH, nor in those of the two brands of HA (Moduretic and Amitrid) were found. Similarly, the plasma concentrations of hydrochlorthiazide, determined gas chromatographically, were equal after Moduretic and Amitrid tablets. The systemic availability of H was faster in the combination of HA than alone. In the AUC value of H, however, there was no significant difference between HA and H tablets."}
{"id": "PMID:29815", "title": "Long-term effect of pH on B-cell function in isolated islets of Langerhans in tissue culture.", "content": "Collagenase isolated mouse pancreatic islets were maintained in tissue culture for up to 5 months in a culture medium buffered with Hepes and the pH varying between 6.8 and 7.6. The amount of insulin released into the medium and the insulin response to glucose and glucose plus theophylline were measured during the culture period. It was found that islets cultured at pH 7.2 maintained the ability to release insulin into the medium for at least 5 months, which was longer than islets cultured at the other pH values. During the first weeks, the islets cultured at pH 7.6 had a higher response to both glucose and glucose plus theophylline than islets cultured at the other pH values, but later they lost their insulin releasing ability.", "contents": "Long-term effect of pH on B-cell function in isolated islets of Langerhans in tissue culture. Collagenase isolated mouse pancreatic islets were maintained in tissue culture for up to 5 months in a culture medium buffered with Hepes and the pH varying between 6.8 and 7.6. The amount of insulin released into the medium and the insulin response to glucose and glucose plus theophylline were measured during the culture period. It was found that islets cultured at pH 7.2 maintained the ability to release insulin into the medium for at least 5 months, which was longer than islets cultured at the other pH values. During the first weeks, the islets cultured at pH 7.6 had a higher response to both glucose and glucose plus theophylline than islets cultured at the other pH values, but later they lost their insulin releasing ability."}
{"id": "PMID:29817", "title": "Cyclic nucleotide-dependent phosphorylation of rat intestinal microvillus and basal-lateral membrane proteins by an endogenous protein kinase.", "content": "Both the microvillus and basal-lateral membrane components of intestinal epithelial cells were found to contain endogenous cyclic nucleotide-dependent protein kinases and their endogenous protein substrates. The phosphorylation of either membrane component using [gamma-32P]ATP as substrate, occurred very rapidly, reaching maximal levels at 1 min. Both cyclic AMP and cyclic GMP were shown to stimulate the phosphorylation of the microvillus and basal-lateral membranes; the approximate concentrations of cyclic AMP and cyclic GMP required for half-maximal stimulation of phosphorylation were 2 x 10(-7) M and 1.7 x 10(-8) M, respectively, for the basal-lateral membranes, and 2 x 10(-7) M and 3.2 x 10(-8) M, respectively, for the microvillus membranes. Although both membrane components were phosphorylated by an endogenous protein kinase, the microvillus membrane was consistently phosphorylated to a greater extent at maximally effective concentrations of either cyclic nucleotide. The microvillus and basal-lateral membranes were also found to contain a phosphoprotein phosphatase; however, the rate of removal of [32P]phosphate from the microvillus membrane was found to be more rapid. Neither cyclic AMP nor cyclic GMP altered the activity of the enzyme in either membrane. The present results together with earlier studies are compatible with the possibility that the regulation of water and electrolyte transport in the small intestine by cyclic AMP and cyclic GMP may be mediated through modulation of the phosphorylation of protein components of the microvillus and basal-lateral membranes.", "contents": "Cyclic nucleotide-dependent phosphorylation of rat intestinal microvillus and basal-lateral membrane proteins by an endogenous protein kinase. Both the microvillus and basal-lateral membrane components of intestinal epithelial cells were found to contain endogenous cyclic nucleotide-dependent protein kinases and their endogenous protein substrates. The phosphorylation of either membrane component using [gamma-32P]ATP as substrate, occurred very rapidly, reaching maximal levels at 1 min. Both cyclic AMP and cyclic GMP were shown to stimulate the phosphorylation of the microvillus and basal-lateral membranes; the approximate concentrations of cyclic AMP and cyclic GMP required for half-maximal stimulation of phosphorylation were 2 x 10(-7) M and 1.7 x 10(-8) M, respectively, for the basal-lateral membranes, and 2 x 10(-7) M and 3.2 x 10(-8) M, respectively, for the microvillus membranes. Although both membrane components were phosphorylated by an endogenous protein kinase, the microvillus membrane was consistently phosphorylated to a greater extent at maximally effective concentrations of either cyclic nucleotide. The microvillus and basal-lateral membranes were also found to contain a phosphoprotein phosphatase; however, the rate of removal of [32P]phosphate from the microvillus membrane was found to be more rapid. Neither cyclic AMP nor cyclic GMP altered the activity of the enzyme in either membrane. The present results together with earlier studies are compatible with the possibility that the regulation of water and electrolyte transport in the small intestine by cyclic AMP and cyclic GMP may be mediated through modulation of the phosphorylation of protein components of the microvillus and basal-lateral membranes."}
{"id": "PMID:29820", "title": "[Initial experience with a tocolysis ward (author's transl)].", "content": "Premature labour is best treated in a special ward, the tocolysis ward. From 1972 to 1975 there were around 8% premature deliveries. During the first six months of 1976 there were still around 8% premature deliveries. During the second six months of 1976 the premature rate was lowered to 6% in the tocolysis ward. This is a decrease of the 25%.", "contents": "[Initial experience with a tocolysis ward (author's transl)]. Premature labour is best treated in a special ward, the tocolysis ward. From 1972 to 1975 there were around 8% premature deliveries. During the first six months of 1976 there were still around 8% premature deliveries. During the second six months of 1976 the premature rate was lowered to 6% in the tocolysis ward. This is a decrease of the 25%."}
{"id": "PMID:29824", "title": "Genetic studies of acridine-induced mutants in Streptococcus pneumoniae.", "content": "The mutagenic properties of acridines on pneumococcus are described. All seven acridines tested were mutagenic at the amiA locus conferring a resistance to 10(-5) M aminopterin. The effects of quinacrine were more specifically investigated. It was observed that: mutants can be obtained only by treatment of exponentially growing cells; a sharp maximum mutagenic effect occurs at a concentration slightly lower than the bacteriostatic value; and the amount of quinacrine required to yield the maximum mutagenic effect decreases with the pH of the medium. Moreover, the number of mutants detected after quinacrine treatment varies from locus to locus. The majority of quinacrine-induced mutants are readily reverted by quinacrine, but not by nitrosoguanidine treatment. This suggests that in pneumococcus quinacrine induces mainly frameshift mutations. A further study of the revertants obtained by quinacrine treatment of quinacrine-induced mutants strengths this interpretation: most of the revertants result from a mutation at the same site; some partial revertants exhibiting an intermediate resistance to aminopterin were found to contain two very closely linked mutated sites, each mutation conferring the maximum level of resistance to aminopterin. Thus, the majority of quinacrine-induced mutants at the amiA locus of pneumococcus consists of frameshift mutations. Nearly all of the isolated mutants induced by quinacrine as well as other acridines belong to the low efficiency class of transformation. It was concluded that the mismatch resulting from the pairing between the wild type and the frameshift-containing sequence is recognized by the excision-repair system involved in the discrimination function in a way similar to that in which it recognizes mismatched base pairs between a transition mutation and the wild-type sequence.", "contents": "Genetic studies of acridine-induced mutants in Streptococcus pneumoniae. The mutagenic properties of acridines on pneumococcus are described. All seven acridines tested were mutagenic at the amiA locus conferring a resistance to 10(-5) M aminopterin. The effects of quinacrine were more specifically investigated. It was observed that: mutants can be obtained only by treatment of exponentially growing cells; a sharp maximum mutagenic effect occurs at a concentration slightly lower than the bacteriostatic value; and the amount of quinacrine required to yield the maximum mutagenic effect decreases with the pH of the medium. Moreover, the number of mutants detected after quinacrine treatment varies from locus to locus. The majority of quinacrine-induced mutants are readily reverted by quinacrine, but not by nitrosoguanidine treatment. This suggests that in pneumococcus quinacrine induces mainly frameshift mutations. A further study of the revertants obtained by quinacrine treatment of quinacrine-induced mutants strengths this interpretation: most of the revertants result from a mutation at the same site; some partial revertants exhibiting an intermediate resistance to aminopterin were found to contain two very closely linked mutated sites, each mutation conferring the maximum level of resistance to aminopterin. Thus, the majority of quinacrine-induced mutants at the amiA locus of pneumococcus consists of frameshift mutations. Nearly all of the isolated mutants induced by quinacrine as well as other acridines belong to the low efficiency class of transformation. It was concluded that the mismatch resulting from the pairing between the wild type and the frameshift-containing sequence is recognized by the excision-repair system involved in the discrimination function in a way similar to that in which it recognizes mismatched base pairs between a transition mutation and the wild-type sequence."}
{"id": "PMID:29826", "title": "[Effects of psychotropic drugs on the spinal ventral root reflexes in cats. A comparison of the depressant actions in intact and spinal preparations (author's transl)].", "content": "Effects of the typical psychotropic drugs such as neuroleptics, tricyclic antidepressants and benzodiazepines on the monosynaptic reflex (MSR) and polysynaptic reflex (PSR) were investigated using intact and spinal cats. Drugs used were chlorpromazine, levomepromazine, perphenazine, prochlorperazine, droperidol, haloperidol, amitriptyline, imipramine, diazepam and flurazepam. Neuroleptics depressed the ventral root reflexes markedly to slightly in both preparations. The inhibitory effects of these drugs on MSR of intact cats were stronger than those on MSR of spinal cats, and the activity was slightly higher than that of PSR depression in intact preparations. In intact cats, those depressants effects of neuroleptics on PSR produced various characteristic action patterns in comparison with MSR inhibition. Tricyclic antidepressants were similar in the mode of action to the dimethylamino side-chain groups in phenothiazines, but the inhibitory effects of ventral root reflexes were distinctly weaker than that of neuroleptics. Benzodiazepines depressed only PSR without MSR inhibition, especially in spinal cats. Thus, it is suggested that the structure-activity relationship considered, a classification of the psychotropic drugs can be given according to the inhibitory activities on spinal ventral root reflexes in intact and spinal cats.", "contents": "[Effects of psychotropic drugs on the spinal ventral root reflexes in cats. A comparison of the depressant actions in intact and spinal preparations (author's transl)]. Effects of the typical psychotropic drugs such as neuroleptics, tricyclic antidepressants and benzodiazepines on the monosynaptic reflex (MSR) and polysynaptic reflex (PSR) were investigated using intact and spinal cats. Drugs used were chlorpromazine, levomepromazine, perphenazine, prochlorperazine, droperidol, haloperidol, amitriptyline, imipramine, diazepam and flurazepam. Neuroleptics depressed the ventral root reflexes markedly to slightly in both preparations. The inhibitory effects of these drugs on MSR of intact cats were stronger than those on MSR of spinal cats, and the activity was slightly higher than that of PSR depression in intact preparations. In intact cats, those depressants effects of neuroleptics on PSR produced various characteristic action patterns in comparison with MSR inhibition. Tricyclic antidepressants were similar in the mode of action to the dimethylamino side-chain groups in phenothiazines, but the inhibitory effects of ventral root reflexes were distinctly weaker than that of neuroleptics. Benzodiazepines depressed only PSR without MSR inhibition, especially in spinal cats. Thus, it is suggested that the structure-activity relationship considered, a classification of the psychotropic drugs can be given according to the inhibitory activities on spinal ventral root reflexes in intact and spinal cats."}
{"id": "PMID:29827", "title": "[Behavioral and EEG effects of triazolam in comparison with those of diazepam (author's transl)].", "content": "Triazolam was 4 to 5 times as potent as diazepam in reducing hyperemotionality of either septal-lesioned or olfactory bulbectomized rats (O.B. rats), and in suppressing muricide in O.B. rats. This agent was equipotent with diazepam in inhibiting fighting behavior of long-term isolated mice, but was longer in duration of action. Triazolam was approximately 4 times more potent than diazepam in preventing pentetrazol convulsion, but was 10 times less potent in inhibiting maximal electroshock convulsion in mice. The muscle relaxant effect of triazolam as assessed by the inclined screen test was 34 times, and the effect on rotarod performance was 17 times more potent than that of diazepam in mice. Triazolam (0.2 approximately 0.5 mg/kg i.v.) changed the EEG to a drowsy pattern in unanesthetized rabbits with a chronic electrode implant, and suppressed the EEG arousal response to auditory stimulation and electrical stimulation given to either the mesencephalic reticular formation or posterior hypothalamus. The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation were also markedly inhibited by triazolam. These EEG effects of triazolam were qualitatively similar to, but were 4 to 5 times more potent than those of diazepam. These results indicate that triazolam is a potent tranquilizer with a longer duration of action, and the muscle relaxant effect is considerable as compared with diazepam.", "contents": "[Behavioral and EEG effects of triazolam in comparison with those of diazepam (author's transl)]. Triazolam was 4 to 5 times as potent as diazepam in reducing hyperemotionality of either septal-lesioned or olfactory bulbectomized rats (O.B. rats), and in suppressing muricide in O.B. rats. This agent was equipotent with diazepam in inhibiting fighting behavior of long-term isolated mice, but was longer in duration of action. Triazolam was approximately 4 times more potent than diazepam in preventing pentetrazol convulsion, but was 10 times less potent in inhibiting maximal electroshock convulsion in mice. The muscle relaxant effect of triazolam as assessed by the inclined screen test was 34 times, and the effect on rotarod performance was 17 times more potent than that of diazepam in mice. Triazolam (0.2 approximately 0.5 mg/kg i.v.) changed the EEG to a drowsy pattern in unanesthetized rabbits with a chronic electrode implant, and suppressed the EEG arousal response to auditory stimulation and electrical stimulation given to either the mesencephalic reticular formation or posterior hypothalamus. The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation were also markedly inhibited by triazolam. These EEG effects of triazolam were qualitatively similar to, but were 4 to 5 times more potent than those of diazepam. These results indicate that triazolam is a potent tranquilizer with a longer duration of action, and the muscle relaxant effect is considerable as compared with diazepam."}
{"id": "PMID:29828", "title": "[Effects of triazolam on conditioned behavior in rats (author's transl)].", "content": "Effects of triazolam on various types of conditioned behavior were investigated and compared mainly with diaepam in rats. The active conditioned avoidance response of the rat in a Shuttle box was inhibited by triazolam and diazepam only at large doses. The passive avoidance response in a step-down method was not affected by either triazolam or diazepam, but was markedly suppressed by chlorpromazine. The low rate response of hypothalamic self-stimulation behavior was markedly increased by triazolam at doses ranging from 2 to 40 mg/kg p.o., but was suppressed at doses over 80 mg/kg p.o. The high rate response was unaffected by triazolam even at doses of 40 approximately 180 mg/kg p.o. The low rate response was increased by diazepam at doses of 1 approximately 10 mg/kg p.o. and was suppressed at 80 mg/kg p.o. The high rate response was reduced by diazepam at 180 mg/kg p.o. In the conflict situation of the rat subjected to food reward and foot-shock punishment, the lever press response in the unpunished period was reduced by triazolam at doses of 1 approximately 5 mg/kg p.o., whereas that in the punished period was markedly increased. Similar effects were observed with diazepam at doses of 15 approximately 20 mg/kg p.o. Triazolam appeared to be 10 approximately 15 times more potent than diazepam in this anticonfluct effect. Thus, triazolam appears to be a potent antianxiety agent.", "contents": "[Effects of triazolam on conditioned behavior in rats (author's transl)]. Effects of triazolam on various types of conditioned behavior were investigated and compared mainly with diaepam in rats. The active conditioned avoidance response of the rat in a Shuttle box was inhibited by triazolam and diazepam only at large doses. The passive avoidance response in a step-down method was not affected by either triazolam or diazepam, but was markedly suppressed by chlorpromazine. The low rate response of hypothalamic self-stimulation behavior was markedly increased by triazolam at doses ranging from 2 to 40 mg/kg p.o., but was suppressed at doses over 80 mg/kg p.o. The high rate response was unaffected by triazolam even at doses of 40 approximately 180 mg/kg p.o. The low rate response was increased by diazepam at doses of 1 approximately 10 mg/kg p.o. and was suppressed at 80 mg/kg p.o. The high rate response was reduced by diazepam at 180 mg/kg p.o. In the conflict situation of the rat subjected to food reward and foot-shock punishment, the lever press response in the unpunished period was reduced by triazolam at doses of 1 approximately 5 mg/kg p.o., whereas that in the punished period was markedly increased. Similar effects were observed with diazepam at doses of 15 approximately 20 mg/kg p.o. Triazolam appeared to be 10 approximately 15 times more potent than diazepam in this anticonfluct effect. Thus, triazolam appears to be a potent antianxiety agent."}
{"id": "PMID:29829", "title": "D-Amino acids of the amino acid pool and occurrence of racemase and D-amino acid oxidase activities in Escherichia coli B.", "content": "Less than 20% of the amino acid content of the amino acid pool of Escherichia coli B exists in the D-form. Alanine, glutamic acid, and valine were shown by gas- chromatography to be partially in the D-form. Only D-alanine was formed by racemization in the crude extract of this organism. Alanine racemase was easily released from the membranes or vesicles but D-alanine oxidase activity remained firmly bound to the membrane. Most protein amino acids stimulated proline uptake into the vesicles, and the oxidative deamination activities were verified by the proline uptake stimulating amino acids. It is concluded that the obligatory pathway of L-amino acid--D-amino acid--oxo acid which exists in the oxidation of L-alanine does not exist with other L-amino acids. It is likely that other D-amino acids in the pool are formed in the presence of D-amino acid oxidase or D-amino acid aminotransferase.", "contents": "D-Amino acids of the amino acid pool and occurrence of racemase and D-amino acid oxidase activities in Escherichia coli B. Less than 20% of the amino acid content of the amino acid pool of Escherichia coli B exists in the D-form. Alanine, glutamic acid, and valine were shown by gas- chromatography to be partially in the D-form. Only D-alanine was formed by racemization in the crude extract of this organism. Alanine racemase was easily released from the membranes or vesicles but D-alanine oxidase activity remained firmly bound to the membrane. Most protein amino acids stimulated proline uptake into the vesicles, and the oxidative deamination activities were verified by the proline uptake stimulating amino acids. It is concluded that the obligatory pathway of L-amino acid--D-amino acid--oxo acid which exists in the oxidation of L-alanine does not exist with other L-amino acids. It is likely that other D-amino acids in the pool are formed in the presence of D-amino acid oxidase or D-amino acid aminotransferase."}
{"id": "PMID:29830", "title": "[Absorption in the human small intestine relative to the intraluminal milieu].", "content": "The bulk of water and electrolyte absorption takes place in the human jejunum from isotonic solutions, and is determined largely by special transport mechanisms for different monosaccharides, amino acids and dipeptides. This is of considerable significance for regaining the large volumes of fluid delivered to the small intestine during the digestion of food. Small changes in intraluminal pH do not significantly influence the absorptive function of the jejunum and are rapidly compensated by the buffering capacity of the gut. The maintenance of an isotonic as well as neutral intraluminal milieu seems to be essential to the physiological processes of intestinal absorption.", "contents": "[Absorption in the human small intestine relative to the intraluminal milieu]. The bulk of water and electrolyte absorption takes place in the human jejunum from isotonic solutions, and is determined largely by special transport mechanisms for different monosaccharides, amino acids and dipeptides. This is of considerable significance for regaining the large volumes of fluid delivered to the small intestine during the digestion of food. Small changes in intraluminal pH do not significantly influence the absorptive function of the jejunum and are rapidly compensated by the buffering capacity of the gut. The maintenance of an isotonic as well as neutral intraluminal milieu seems to be essential to the physiological processes of intestinal absorption."}
{"id": "PMID:29831", "title": "[Psychotropic drugs as tools for clinical research into schizophrenia (author's transl)].", "content": "There is considerable similarity between paranoid schizophrenia and psychoses provoked by dopaminergic overstimulation in the central nervous system. The fact that neuroleptics are able to block dopaminergic neural activity has led to the hypothesis that there might exist a common biochemical substrate for schizophrenia and e. g. the amphetamine psychoses. Dopaminergic overstimulation may be elicited by different drugs interacting with the dopamine metabolism e. g. dopamine-beta-hydroxylase inhibition (disulfiram, fusaric acid); monoamine-oxidase-inhibition (phenelzine, tranylcypromine); dopamine release (amphetamine); stimulation of postsynaptic dopamine receptors (bromocriptine, apomorphine). Resulting psychotic symptoms consist of ideas of reference, delusions, visual and acustic hallucinations in a clear setting of consciousness. Psychoses occur usually in subjects, who have suffered from various psychiatric illnesses, which have apparently in common a reduced monoamine-oxidase activity in platelets. It is concluded from various biochemical findings, that psychoses resulting from dopaminergic overstimulation and schizophrenia have different biological substrates.", "contents": "[Psychotropic drugs as tools for clinical research into schizophrenia (author's transl)]. There is considerable similarity between paranoid schizophrenia and psychoses provoked by dopaminergic overstimulation in the central nervous system. The fact that neuroleptics are able to block dopaminergic neural activity has led to the hypothesis that there might exist a common biochemical substrate for schizophrenia and e. g. the amphetamine psychoses. Dopaminergic overstimulation may be elicited by different drugs interacting with the dopamine metabolism e. g. dopamine-beta-hydroxylase inhibition (disulfiram, fusaric acid); monoamine-oxidase-inhibition (phenelzine, tranylcypromine); dopamine release (amphetamine); stimulation of postsynaptic dopamine receptors (bromocriptine, apomorphine). Resulting psychotic symptoms consist of ideas of reference, delusions, visual and acustic hallucinations in a clear setting of consciousness. Psychoses occur usually in subjects, who have suffered from various psychiatric illnesses, which have apparently in common a reduced monoamine-oxidase activity in platelets. It is concluded from various biochemical findings, that psychoses resulting from dopaminergic overstimulation and schizophrenia have different biological substrates."}
{"id": "PMID:29832", "title": "[Indicated and non-indicated administration of antibiotics in surgery (author's transl)].", "content": "Considerations and own experience regarding prophylactic administration of antibiotics and therapeutic customs in surgery are discussed. Based on own and long-term studies recommendations are given for effective and purposeful use of chemotherapy in surgery.", "contents": "[Indicated and non-indicated administration of antibiotics in surgery (author's transl)]. Considerations and own experience regarding prophylactic administration of antibiotics and therapeutic customs in surgery are discussed. Based on own and long-term studies recommendations are given for effective and purposeful use of chemotherapy in surgery."}
{"id": "PMID:29839", "title": "Epstein-Barr virus infection following bone-marrow transplantation.", "content": "A 12-year-old patient with acute lymphoblastic leukemia received a bone-marrow transplant (BMT) from a matched sibling donor. Nine weeks prior to transplant the donor experienced Epstein-Barr virus (EBV)-induced infectious mononucleosis. The bone-marrow recipient was EBV-negative at the time of transplant; however, 4 weeks post transplant the recipient developed clinical symptoms of graft-verus-host disease (GVHD) coincident with serological evidence of acute EBV infection. In addition, a lymphoblastoid cell line positive for Epstein-Barr nuclear antigen was established from a bone-marrow sample obtained at the onset of symptoms compatible with GVHD. Sera obtained from the recipient over the ensuing 2 months showed the appearance of antibodies to specific EBV antigens consistent with a primary immune response to EBV infection. This association of acute EBV infection with symptoms of GVHD in a BMT recipient suggests a need for further investigation of the epidemiology of EBV infections in human bone-marrow transplantation and the relationship between EBV infection and GVHD.", "contents": "Epstein-Barr virus infection following bone-marrow transplantation. A 12-year-old patient with acute lymphoblastic leukemia received a bone-marrow transplant (BMT) from a matched sibling donor. Nine weeks prior to transplant the donor experienced Epstein-Barr virus (EBV)-induced infectious mononucleosis. The bone-marrow recipient was EBV-negative at the time of transplant; however, 4 weeks post transplant the recipient developed clinical symptoms of graft-verus-host disease (GVHD) coincident with serological evidence of acute EBV infection. In addition, a lymphoblastoid cell line positive for Epstein-Barr nuclear antigen was established from a bone-marrow sample obtained at the onset of symptoms compatible with GVHD. Sera obtained from the recipient over the ensuing 2 months showed the appearance of antibodies to specific EBV antigens consistent with a primary immune response to EBV infection. This association of acute EBV infection with symptoms of GVHD in a BMT recipient suggests a need for further investigation of the epidemiology of EBV infections in human bone-marrow transplantation and the relationship between EBV infection and GVHD."}
{"id": "PMID:29840", "title": "Rate constants of absorption versus physico-chemical parameters.", "content": "We examined the velocity constants of buccal absorption in the case of 10 drugs. The measurements tending towards what is the coherence between the velocity constants and the physico-chemical parameters of the drugs. On the basis of our investigations one can see that the dipol moment offers more reliable information for the size of the velocity of absorption than the lipid-water distribution ratio, molecular radii or diffusion constants. Our opinion is that it can be useful in modifying and planning the drug molecules.", "contents": "Rate constants of absorption versus physico-chemical parameters. We examined the velocity constants of buccal absorption in the case of 10 drugs. The measurements tending towards what is the coherence between the velocity constants and the physico-chemical parameters of the drugs. On the basis of our investigations one can see that the dipol moment offers more reliable information for the size of the velocity of absorption than the lipid-water distribution ratio, molecular radii or diffusion constants. Our opinion is that it can be useful in modifying and planning the drug molecules."}
{"id": "PMID:29842", "title": "Photolytic inhibition and labeling of proteins with aryl diazonium compounds.", "content": "In the course of preparing aryl azide derivatives for use as photoprobes, we have observed significant light sensitivity in the precursor aryl diazonium compounds. The photosensitive properties of this class of compounds are of interest since they will seek out cationic binding sites in biological targets, and can be employed to inhibit complementary targets at acid pH. The relationship between photolytic change in the structure of diazonium compounds and the corresponding change in function of a biological target are presented. Experiments are described in which the dark and light sensitive properties of a model diazonium compound, diazobenzene sulfonate (DBS), were determined. The ultraviolet spectra were used to evaluate the dark stability and light sensitivity of DBS. Chymotrypsin and trypsin served as functioning targets for further evaluation of the photochemical properties. Both enzymes are stable to the probe in the dark at acid pH. A rapid loss of enzyme activity was observed following flash photolysis of DBS-enzyme solutions. Photolytic incorporation of radioactive DBS into chymotrypsin was observed. Aryl diazonium salts can be employed to probe the availability of complementary sites in biological targets at different acid pH values.", "contents": "Photolytic inhibition and labeling of proteins with aryl diazonium compounds. In the course of preparing aryl azide derivatives for use as photoprobes, we have observed significant light sensitivity in the precursor aryl diazonium compounds. The photosensitive properties of this class of compounds are of interest since they will seek out cationic binding sites in biological targets, and can be employed to inhibit complementary targets at acid pH. The relationship between photolytic change in the structure of diazonium compounds and the corresponding change in function of a biological target are presented. Experiments are described in which the dark and light sensitive properties of a model diazonium compound, diazobenzene sulfonate (DBS), were determined. The ultraviolet spectra were used to evaluate the dark stability and light sensitivity of DBS. Chymotrypsin and trypsin served as functioning targets for further evaluation of the photochemical properties. Both enzymes are stable to the probe in the dark at acid pH. A rapid loss of enzyme activity was observed following flash photolysis of DBS-enzyme solutions. Photolytic incorporation of radioactive DBS into chymotrypsin was observed. Aryl diazonium salts can be employed to probe the availability of complementary sites in biological targets at different acid pH values."}
{"id": "PMID:29843", "title": "The denaturation of covalently inhibited swine pepsin.", "content": "Studies are reported on the denaturation of freshly prepared, intact swine pepsin, which was inactivated by reaction with diazoacetylglycine ethyl ester, to prevent autolysis. Denaturation about pH 6 was found to involve a small expansion of the molecular domain with some loss of organized secondary structure. On the other hand, increasing concentrations of guanidine hydrochloride induced cooperative transitions in both the native and alkali denatured forms to give a cross-linked random coil. No conditions could be found in which these reactions were reversible. Removal of denaturing conditions usually resulted in aggregation and precipitation of protein. From these studies, it would seem that the active conformation is largely predetermined in the zymogen.", "contents": "The denaturation of covalently inhibited swine pepsin. Studies are reported on the denaturation of freshly prepared, intact swine pepsin, which was inactivated by reaction with diazoacetylglycine ethyl ester, to prevent autolysis. Denaturation about pH 6 was found to involve a small expansion of the molecular domain with some loss of organized secondary structure. On the other hand, increasing concentrations of guanidine hydrochloride induced cooperative transitions in both the native and alkali denatured forms to give a cross-linked random coil. No conditions could be found in which these reactions were reversible. Removal of denaturing conditions usually resulted in aggregation and precipitation of protein. From these studies, it would seem that the active conformation is largely predetermined in the zymogen."}
{"id": "PMID:29857", "title": "Cornea endothelial bicarbonate fluxes following preservation in solutions of varying composition.", "content": "Numerous modifications have been made in MK solution, primarily concerned with alterations in both bicarbonate concentration and PCO2. Variations of the solutions from high bicarbonate to low bicarbonate and either high or low PCO2 were made which resulted in a decreased net bicarbonate flux across the endothelium after a 3-day storage period. Even with drastic changes in the storage solution there was a relatively small change in the net bicarbonate flux. Higher passive fluxes were found at a pH above 8, and a higher net flux with a bicarbonate concentration of 17.5 nM or higher. Variation in PCO2 made little difference to the net endothelial fluxes; when a high PCO2 was used, there was a concurrent elevation of PO2 in the storage solution, but no beneficial effect was found on the endothelial transport system. It was apparent that a good storage solution contained a buffer (bicarbonate was better than phosphate) and 5% dextran and was at a neutral pH (between 7 and 8).", "contents": "Cornea endothelial bicarbonate fluxes following preservation in solutions of varying composition. Numerous modifications have been made in MK solution, primarily concerned with alterations in both bicarbonate concentration and PCO2. Variations of the solutions from high bicarbonate to low bicarbonate and either high or low PCO2 were made which resulted in a decreased net bicarbonate flux across the endothelium after a 3-day storage period. Even with drastic changes in the storage solution there was a relatively small change in the net bicarbonate flux. Higher passive fluxes were found at a pH above 8, and a higher net flux with a bicarbonate concentration of 17.5 nM or higher. Variation in PCO2 made little difference to the net endothelial fluxes; when a high PCO2 was used, there was a concurrent elevation of PO2 in the storage solution, but no beneficial effect was found on the endothelial transport system. It was apparent that a good storage solution contained a buffer (bicarbonate was better than phosphate) and 5% dextran and was at a neutral pH (between 7 and 8)."}
{"id": "PMID:29860", "title": "Thymic humoral factor in the assessment of T lymphocytics in a patient with T cell chronic lymphocyte leukemia.", "content": "Peripheral blood lymphocytes from a patient with T cell chronic lymphocytic leukemia were examined by a combination of cell markers (E and M rosettes, and surface Ig), the graft-vs.-host reaction, thymic humoral factor (THF) and scanning electron microscopy. It was not possible, at first, to determine by conventional methods whether the leukemic cells were of the B or T type, but the THF and graft-vs.-host reaction showed that T cell precursors were present. These cells were incompetent immature T cells that underwent maturation following treatment with THF. Three months later, the T cell nature of the disease was clearly demonstrated by the E rosette technique, although at this time the cells were no longer influenced by THF.", "contents": "Thymic humoral factor in the assessment of T lymphocytics in a patient with T cell chronic lymphocyte leukemia. Peripheral blood lymphocytes from a patient with T cell chronic lymphocytic leukemia were examined by a combination of cell markers (E and M rosettes, and surface Ig), the graft-vs.-host reaction, thymic humoral factor (THF) and scanning electron microscopy. It was not possible, at first, to determine by conventional methods whether the leukemic cells were of the B or T type, but the THF and graft-vs.-host reaction showed that T cell precursors were present. These cells were incompetent immature T cells that underwent maturation following treatment with THF. Three months later, the T cell nature of the disease was clearly demonstrated by the E rosette technique, although at this time the cells were no longer influenced by THF."}
{"id": "PMID:29863", "title": "Detection of lipopolysaccharide in suspected bacteriuric urine using a carbocyanine dye.", "content": "Currently practiced methods for the detection of gram negative bacteriuria require culturing and overnight incubation. Such an approach to bacteriuria detection is unacceptable for any screening program which requires rapid presumptive evidence of infection. In this study, the lipopolysaccharide-dependent formation of a unique dye absorption spectra of the cationic carbocyanine dye, 1-ethyl-2-[3-(1-ethylnaphtho[1,2d]-thiazolin-2-ylidene)-2-methylpropenyl] naphtho[1,2d]-thiazolium bromide, was used to detect bacteriuria caused by gram negative organisms in a hospitalized population. In an evaluation of 168 first morning and randomly collected suspected bacteriuric urines, the dye test detected 66% of the loop plate positive urines with false positive and false negative values of 28% and 34%, respectively. However, 37% of the false positive results occurred in urines containing less than 10(5) gram negative bacteria/ml and an additional 24% of the false positives were seen for patients currently receiving antibiotic treatment. Urine specimens were also evaluated using the limulus lysate assay for lipopolysaccharide.", "contents": "Detection of lipopolysaccharide in suspected bacteriuric urine using a carbocyanine dye. Currently practiced methods for the detection of gram negative bacteriuria require culturing and overnight incubation. Such an approach to bacteriuria detection is unacceptable for any screening program which requires rapid presumptive evidence of infection. In this study, the lipopolysaccharide-dependent formation of a unique dye absorption spectra of the cationic carbocyanine dye, 1-ethyl-2-[3-(1-ethylnaphtho[1,2d]-thiazolin-2-ylidene)-2-methylpropenyl] naphtho[1,2d]-thiazolium bromide, was used to detect bacteriuria caused by gram negative organisms in a hospitalized population. In an evaluation of 168 first morning and randomly collected suspected bacteriuric urines, the dye test detected 66% of the loop plate positive urines with false positive and false negative values of 28% and 34%, respectively. However, 37% of the false positive results occurred in urines containing less than 10(5) gram negative bacteria/ml and an additional 24% of the false positives were seen for patients currently receiving antibiotic treatment. Urine specimens were also evaluated using the limulus lysate assay for lipopolysaccharide."}
{"id": "PMID:29864", "title": "[Conservative drug therapy of neurogenic bladder disorders].", "content": "Today neuropharmacas are a helpful part in the conservative treatment of the neurogenic bladder disorders. They are, or course, no \"wonder-drugs\" and usually lead to an improvement only of the troubles, but rarely to complete cure. If monotherapy does not lead to the results wanted, one should combine drugs of the same of similar effects but with different pharmacologic targets. A real progress was reached through alpha-receptor-blockers, whose use has, especially in children with myelomeningocele, changed the therapeutic concept in favour of a largely conservative treatment. We already know a number of substances that in one way or other influence the muscles of the bladder and the bladder outlet. If only part of them will reach clinical usage, it can be assumed that the pharmacotherapy will become even more meaningful in the treatment of neurogenic bladder disorders.", "contents": "[Conservative drug therapy of neurogenic bladder disorders]. Today neuropharmacas are a helpful part in the conservative treatment of the neurogenic bladder disorders. They are, or course, no \"wonder-drugs\" and usually lead to an improvement only of the troubles, but rarely to complete cure. If monotherapy does not lead to the results wanted, one should combine drugs of the same of similar effects but with different pharmacologic targets. A real progress was reached through alpha-receptor-blockers, whose use has, especially in children with myelomeningocele, changed the therapeutic concept in favour of a largely conservative treatment. We already know a number of substances that in one way or other influence the muscles of the bladder and the bladder outlet. If only part of them will reach clinical usage, it can be assumed that the pharmacotherapy will become even more meaningful in the treatment of neurogenic bladder disorders."}
{"id": "PMID:29865", "title": "[Quantitative determination of phosphates in urinary calculi and their matrices].", "content": "The question whether the phosphate participates actively in the calculogenesis or whether it is only an accidental enclosure in the stone material can, in our opinion, only be answered by the quantitative determination of phosphorus in the stone material resp. in the organic stone matrix. The high enrichment of phosphorus in the stone material, in comparison with the urine, as well as its additional significant enrichment in the stone matrix, compared with the (crystalline) stone material, both deduced from our analytical data, nearly exclude a passive role of the phosphate in the calculogenesis. On the basis of our investigation we suppose that the phosphate crystalluriae, occurring spontaneously or induced, at moderate pH-values of urine, especially by Ca-oxalate, sometimes by urate crystalluriae, contribute to the crystal \"density\" in the urine, the sufficient crystal \"density\" being one of the preconditions for the formation of compact crystal aggregates; the other precondition is the presence of the reactive organic cement substance in a sufficient concentration. This active crystal agglomerating component is represented, in our conception, by partially hemolysed blood cells resp. by the cholesterol of their damaged membranes.", "contents": "[Quantitative determination of phosphates in urinary calculi and their matrices]. The question whether the phosphate participates actively in the calculogenesis or whether it is only an accidental enclosure in the stone material can, in our opinion, only be answered by the quantitative determination of phosphorus in the stone material resp. in the organic stone matrix. The high enrichment of phosphorus in the stone material, in comparison with the urine, as well as its additional significant enrichment in the stone matrix, compared with the (crystalline) stone material, both deduced from our analytical data, nearly exclude a passive role of the phosphate in the calculogenesis. On the basis of our investigation we suppose that the phosphate crystalluriae, occurring spontaneously or induced, at moderate pH-values of urine, especially by Ca-oxalate, sometimes by urate crystalluriae, contribute to the crystal \"density\" in the urine, the sufficient crystal \"density\" being one of the preconditions for the formation of compact crystal aggregates; the other precondition is the presence of the reactive organic cement substance in a sufficient concentration. This active crystal agglomerating component is represented, in our conception, by partially hemolysed blood cells resp. by the cholesterol of their damaged membranes."}
{"id": "PMID:29866", "title": "[Current considerations on male secretory sterility].", "content": "The problems of male sterility are considered in the light of fundamentals underlying the embryology and histophysiology of spermatogenesis and its hormonal control. Some forms of infertility are now understood but no treatment for them has yet been found. The mechanisms of other forms still elude firm definition: this is the case of, among others, some oligoasthenospermias in which, according to our experience, excessive estrogen production appears to play a physiopathologic role. In the prevailing uncertainty about therapeutic methods, the best short-term solutions in this field are in-vitro enhancement of the sperm's fecundating power and the improvement of artificial insemination techniques.", "contents": "[Current considerations on male secretory sterility]. The problems of male sterility are considered in the light of fundamentals underlying the embryology and histophysiology of spermatogenesis and its hormonal control. Some forms of infertility are now understood but no treatment for them has yet been found. The mechanisms of other forms still elude firm definition: this is the case of, among others, some oligoasthenospermias in which, according to our experience, excessive estrogen production appears to play a physiopathologic role. In the prevailing uncertainty about therapeutic methods, the best short-term solutions in this field are in-vitro enhancement of the sperm's fecundating power and the improvement of artificial insemination techniques."}
{"id": "PMID:29867", "title": "Determinants of oxygen uptake during sodium bicarbonate infusion.", "content": "Steady-state passive hyperventilation alkalosis produces a predictable increase in oxygen uptake (VO2) proportional to the change in arterial pH (pHa) while variable changes in VO2 have been reported during alkali infusion. To compare metabolic with respiratory alkalosis 17 dogs were anesthetized with halothane and their VO2 response to respiratory alkalosis evaluated by hyperventilation. The pHa measured during this phase was duplicated during the later continuous infusion of NaHCO3 at which time either 1) ventilation was held constant at the control level, allowing arterial carbon dioxide tension (PaCO2) to rise as a consequence of the bicarbonate dissociation, or 2) PaCO2 was held constant by servo control of ventilation. Hyperventilation (pHa 7.6, PaCO2 13 Torr) produced an average increase in VO2 of 24%. During the bicarbonate infusion at constant ventilation (pHa 7.6, PaCO2 45 Torr) VO2 increased only 7%; however, when PACO2 was held constant by servo ventilation VO2 increased 21% above control. We conclude that respiratory and metabolic alkalosis produce similar increases in VO2 when steady-state acid-base conditions are achieved.", "contents": "Determinants of oxygen uptake during sodium bicarbonate infusion. Steady-state passive hyperventilation alkalosis produces a predictable increase in oxygen uptake (VO2) proportional to the change in arterial pH (pHa) while variable changes in VO2 have been reported during alkali infusion. To compare metabolic with respiratory alkalosis 17 dogs were anesthetized with halothane and their VO2 response to respiratory alkalosis evaluated by hyperventilation. The pHa measured during this phase was duplicated during the later continuous infusion of NaHCO3 at which time either 1) ventilation was held constant at the control level, allowing arterial carbon dioxide tension (PaCO2) to rise as a consequence of the bicarbonate dissociation, or 2) PaCO2 was held constant by servo control of ventilation. Hyperventilation (pHa 7.6, PaCO2 13 Torr) produced an average increase in VO2 of 24%. During the bicarbonate infusion at constant ventilation (pHa 7.6, PaCO2 45 Torr) VO2 increased only 7%; however, when PACO2 was held constant by servo ventilation VO2 increased 21% above control. We conclude that respiratory and metabolic alkalosis produce similar increases in VO2 when steady-state acid-base conditions are achieved."}
{"id": "PMID:29868", "title": "Intracellular pH and bicarbonate concentration in human muscle during recovery from exercise.", "content": "Eight subjects exercised on an ergometer until exhaustion. Femoral venous blood was analyzed for lactate, pyruvate, protein, electrolytes, and acid-base parameters. Muscle samples taken during the recovery period from m. quadriceps femoris were analyzed for water, electrolytes, lactate, and acid-labile CO2. Water content in the muscle biopsy sample was increased after exercise to 78.7 +/- 0.5% compared with the normal 76.7 +/- 0.8% at rest. The distribution of water between the extra- and intracellular space was calculated by the chloride method. In spite of elevated PCO2 in femoral venous blood the content of acid-labile CO2 was decreased in muscle after exercise. One minute after termination of exercise muscle CO2 was about half of the normal content at rest. During the recovery period muscle CO2 increased but was 20 min after termination of exercise still significantly below the value at rest. Intracellular pH (pHi) and bicarbonate concentration ([HCO3-]i) in muscle have been calculated. The validity of the assumptions underlying the calculations are thoroughly discussed. pHi decreased from the normal value at rest, 7.00 +/- 0.06 (mean +/- SD), to about 6.4 after exercise. [HCO3-] decreased from 10.2 +/- 1.2 mmol/l at rest to about 3 mmol/l after exercise. The changes are the greatest so far reported for an in vivo situation. After 20 min recovery pHi was almost the same as at rest, whereas bicarbonate was still well below.", "contents": "Intracellular pH and bicarbonate concentration in human muscle during recovery from exercise. Eight subjects exercised on an ergometer until exhaustion. Femoral venous blood was analyzed for lactate, pyruvate, protein, electrolytes, and acid-base parameters. Muscle samples taken during the recovery period from m. quadriceps femoris were analyzed for water, electrolytes, lactate, and acid-labile CO2. Water content in the muscle biopsy sample was increased after exercise to 78.7 +/- 0.5% compared with the normal 76.7 +/- 0.8% at rest. The distribution of water between the extra- and intracellular space was calculated by the chloride method. In spite of elevated PCO2 in femoral venous blood the content of acid-labile CO2 was decreased in muscle after exercise. One minute after termination of exercise muscle CO2 was about half of the normal content at rest. During the recovery period muscle CO2 increased but was 20 min after termination of exercise still significantly below the value at rest. Intracellular pH (pHi) and bicarbonate concentration ([HCO3-]i) in muscle have been calculated. The validity of the assumptions underlying the calculations are thoroughly discussed. pHi decreased from the normal value at rest, 7.00 +/- 0.06 (mean +/- SD), to about 6.4 after exercise. [HCO3-] decreased from 10.2 +/- 1.2 mmol/l at rest to about 3 mmol/l after exercise. The changes are the greatest so far reported for an in vivo situation. After 20 min recovery pHi was almost the same as at rest, whereas bicarbonate was still well below."}
{"id": "PMID:29871", "title": "On the governance system of university schools of nursing.", "content": "We find ourselves as schools of nursing in a period in which external pressures are increasing on the school and the university as the public and its representatives require better accounting for the resources as assigned to the university and access to the decisions as to the use of the resources. At the same time, our systems of governance are not fully functioning and in many cases the dysfunctions consume faculty time rather than releasing time to the developmental tasks. This situation thus should not be ignored but must be dealt with to permit the growth to proceed.", "contents": "On the governance system of university schools of nursing. We find ourselves as schools of nursing in a period in which external pressures are increasing on the school and the university as the public and its representatives require better accounting for the resources as assigned to the university and access to the decisions as to the use of the resources. At the same time, our systems of governance are not fully functioning and in many cases the dysfunctions consume faculty time rather than releasing time to the developmental tasks. This situation thus should not be ignored but must be dealt with to permit the growth to proceed."}
{"id": "PMID:29877", "title": "Professional interaction in academic health centers.", "content": "A survey was made of 106 medical schools to determine the presence of the academic health center concept in the United States. Five centers were selected for an in-depth study of the attitudes and behavior of health center students, faculty members, and administrators in the professions of dentistry, medicine, nursing and basic science. The results were based on the return of 2,399 questionnaires which investigated the attitudes and behavior of the groups described relative to the health center concept. It was found that attitudes and behavior relative to the health center concept were different among professions, among various statuses of people within professions and among those persons functioning within the various health center administrative structures.", "contents": "Professional interaction in academic health centers. A survey was made of 106 medical schools to determine the presence of the academic health center concept in the United States. Five centers were selected for an in-depth study of the attitudes and behavior of health center students, faculty members, and administrators in the professions of dentistry, medicine, nursing and basic science. The results were based on the return of 2,399 questionnaires which investigated the attitudes and behavior of the groups described relative to the health center concept. It was found that attitudes and behavior relative to the health center concept were different among professions, among various statuses of people within professions and among those persons functioning within the various health center administrative structures."}
{"id": "PMID:29878", "title": "A systematic approach to module development.", "content": "The primary purpose of this article has been to outline and discuss the fourteen steps of the systematic approach to modular development utilized by the author. In addition, examples of each step have been included in an effort to illustrate each point. The article ends with a list of useful resources for the beginning module developer and a statement about the value of each resource.", "contents": "A systematic approach to module development. The primary purpose of this article has been to outline and discuss the fourteen steps of the systematic approach to modular development utilized by the author. In addition, examples of each step have been included in an effort to illustrate each point. The article ends with a list of useful resources for the beginning module developer and a statement about the value of each resource."}
{"id": "PMID:29885", "title": "Time-dependent increase in the stability of collagen fibrils formed in vitro. I. Effects of pH and salt concentration on the dissolution of the fibrils.", "content": "The time-dependent increase in stability, as measured in terms of the rate of dissolution, of collagen fibrils formed in vitro from pepsin-treated collagen was significantly affected only by temperature, and not by either ionic strength or pH. This is in contrast with collagen fibril formation, a process which is greatly affected by ionic strength and pH. Within the range of temperature 29-37 degrees C, lower temperature caused slower fibril formation and faster fibril stabilization. These results suggest that the intermolecular interactions involved in stabilizing collagen fibrils are entirely different from those involved in fibril formation. Based on kinetic analysis of the dissolution and stabilization of the fibrils, it is proposed that collagen molecules first form unstable fibrils which become gradually stabilized on prolonged incubation, without necessarily introducing covalent cross-links.", "contents": "Time-dependent increase in the stability of collagen fibrils formed in vitro. I. Effects of pH and salt concentration on the dissolution of the fibrils. The time-dependent increase in stability, as measured in terms of the rate of dissolution, of collagen fibrils formed in vitro from pepsin-treated collagen was significantly affected only by temperature, and not by either ionic strength or pH. This is in contrast with collagen fibril formation, a process which is greatly affected by ionic strength and pH. Within the range of temperature 29-37 degrees C, lower temperature caused slower fibril formation and faster fibril stabilization. These results suggest that the intermolecular interactions involved in stabilizing collagen fibrils are entirely different from those involved in fibril formation. Based on kinetic analysis of the dissolution and stabilization of the fibrils, it is proposed that collagen molecules first form unstable fibrils which become gradually stabilized on prolonged incubation, without necessarily introducing covalent cross-links."}
{"id": "PMID:29886", "title": "Chymotrypsin inhibitors from hemolymph of the silkworm, Bombyx mori.", "content": "Three new protease inhibitors were isolated and purified about 200-fold from hemolymph of silkworm larvae, Bombyx mori, using ion-exchange and affinity chromatography. Two of the three inhibitors were basic proteins (SCI-I had pI 9.4 and SCI-II had pI 9.6) and one was acidic (SCI-III had pI 4.0). The molecular weight of each inhibitor was determined to be 7,000 by the sedimentation equilibrium method. The amino acid composition of the inhibitors were similar except for the contents of Asp, Glu, Ile, Leu, and Lys. Val, His, and Trp were not present in the inhibitors and Met appeared only in SCI-III. The CD spectra of the inhibitors were all similar and indicated a low content of alpha-helical structure (10% at most). Each inhibitor could inhibit the protease and esterase activities of bovine alpha-chymotrypsin at a one-to-one molar ratio, and the dissociation constants were 3.1 X 10(-9)M for SCI-I and II and 1.3 X 10(-8)M for SCI-III. Only SCI-II showed a weak inhibitory activity against bovine trypsin. Subtilisin BPN' and papain were not inhibited by these inhibitors.", "contents": "Chymotrypsin inhibitors from hemolymph of the silkworm, Bombyx mori. Three new protease inhibitors were isolated and purified about 200-fold from hemolymph of silkworm larvae, Bombyx mori, using ion-exchange and affinity chromatography. Two of the three inhibitors were basic proteins (SCI-I had pI 9.4 and SCI-II had pI 9.6) and one was acidic (SCI-III had pI 4.0). The molecular weight of each inhibitor was determined to be 7,000 by the sedimentation equilibrium method. The amino acid composition of the inhibitors were similar except for the contents of Asp, Glu, Ile, Leu, and Lys. Val, His, and Trp were not present in the inhibitors and Met appeared only in SCI-III. The CD spectra of the inhibitors were all similar and indicated a low content of alpha-helical structure (10% at most). Each inhibitor could inhibit the protease and esterase activities of bovine alpha-chymotrypsin at a one-to-one molar ratio, and the dissociation constants were 3.1 X 10(-9)M for SCI-I and II and 1.3 X 10(-8)M for SCI-III. Only SCI-II showed a weak inhibitory activity against bovine trypsin. Subtilisin BPN' and papain were not inhibited by these inhibitors."}
{"id": "PMID:29887", "title": "An isoelectric focusing study of acid phosphohydrolases in rat liver lysosomes.", "content": "The differentiation of rat liver lysosomal acid phosphatase, acid ATPase, acid phosphodiesterase, acid ribonuclease, and acid deoxyribonuclease was studied by isoelectric focusing. To prevent autolytic digestion, inhibitors of cathepsins and neuraminidase were used. The proportion of acidic forms of acid phosphatase, acid ATPase and acid phosphodiesterase was increased by the use of extraction medium containing 0.05% Triton X-100. To investigate the identity of acid ATPase and acid phosphodiesterase, the relative activities among the multiple forms of these enzymes, the acid phosphodiesterase/acid ATPase ratio at each activity peak, and the degree of enzyme inhibition by p-chloromercuriphenyl sulfonic acid were estimated. The results suggest that acid ATPase is not identical with acid phosphodiesterase. With extraction medium free of Triton X-100, acid ribonuclease appeared in two forms. However, in addition to these forms, a new form of this enzyme with a more acidic pI (4.22) emerged when extraction medium containing 0.05% Triton X-100 was used. The major peak of acid deoxyribonuclease with pI=8.40-9.39 was obtained regardless of the extracting method.", "contents": "An isoelectric focusing study of acid phosphohydrolases in rat liver lysosomes. The differentiation of rat liver lysosomal acid phosphatase, acid ATPase, acid phosphodiesterase, acid ribonuclease, and acid deoxyribonuclease was studied by isoelectric focusing. To prevent autolytic digestion, inhibitors of cathepsins and neuraminidase were used. The proportion of acidic forms of acid phosphatase, acid ATPase and acid phosphodiesterase was increased by the use of extraction medium containing 0.05% Triton X-100. To investigate the identity of acid ATPase and acid phosphodiesterase, the relative activities among the multiple forms of these enzymes, the acid phosphodiesterase/acid ATPase ratio at each activity peak, and the degree of enzyme inhibition by p-chloromercuriphenyl sulfonic acid were estimated. The results suggest that acid ATPase is not identical with acid phosphodiesterase. With extraction medium free of Triton X-100, acid ribonuclease appeared in two forms. However, in addition to these forms, a new form of this enzyme with a more acidic pI (4.22) emerged when extraction medium containing 0.05% Triton X-100 was used. The major peak of acid deoxyribonuclease with pI=8.40-9.39 was obtained regardless of the extracting method."}
{"id": "PMID:29888", "title": "Mechanisms of desorption and adsorption of liver cytosolic fumarase to cellular membranous components.", "content": "The cytosolic fumarase [EC 4.2.1.2[ of rat liver was bound, after dialysis, to the microsomal membrane in vitro. Binding of the enzyme was dependent on pH, and was facilitated in the pH range below 7.5. The binding reaction was completely inhibited by 0.5 mM fumarate, aurintricarboxylate or colchicine. The bound fumarase was released from the membrane by the substrates, isocitrate, citrate or 2,3-diphosphoglycerate at low concentrations. Desorption of the enzyme by metabolites was also dependent on pH, and was more rapid in the alkaline pH range. The enzyme desorption curves were sigmoidal, and kinetic studies suggested a biphasic cooperative mechanism for the action of the metabolites. The apparent desorption constants (concentrations necessary for 50% desorption of the enzyme) estimated at pH 7.3 for isocitrate, 2,3-diphosphoglycerate, L-malate, oxalacetate, fumarate, citrate, succinate, and KCl were 0.073, 0.074, 0.22, 0.39, 0.56, 2.9, and 19 mM, respectively. The bound fumarase showed little enzymatic activity, and its Km and Vmax values were fivefold and 31%, respectively, of those of the free enzyme.", "contents": "Mechanisms of desorption and adsorption of liver cytosolic fumarase to cellular membranous components. The cytosolic fumarase [EC 4.2.1.2[ of rat liver was bound, after dialysis, to the microsomal membrane in vitro. Binding of the enzyme was dependent on pH, and was facilitated in the pH range below 7.5. The binding reaction was completely inhibited by 0.5 mM fumarate, aurintricarboxylate or colchicine. The bound fumarase was released from the membrane by the substrates, isocitrate, citrate or 2,3-diphosphoglycerate at low concentrations. Desorption of the enzyme by metabolites was also dependent on pH, and was more rapid in the alkaline pH range. The enzyme desorption curves were sigmoidal, and kinetic studies suggested a biphasic cooperative mechanism for the action of the metabolites. The apparent desorption constants (concentrations necessary for 50% desorption of the enzyme) estimated at pH 7.3 for isocitrate, 2,3-diphosphoglycerate, L-malate, oxalacetate, fumarate, citrate, succinate, and KCl were 0.073, 0.074, 0.22, 0.39, 0.56, 2.9, and 19 mM, respectively. The bound fumarase showed little enzymatic activity, and its Km and Vmax values were fivefold and 31%, respectively, of those of the free enzyme."}
{"id": "PMID:29889", "title": "Ribonuclease H from rat liver. I. Partial purification and characterization of nuclear ribonuclease H1.", "content": "A ribonuclease H, an enzyme that specifically degrades the RNA moiety of RNA-DNA hybrid, has been partially purified from rat liver nuclei and characterized. Neither native or denatured DNA, nor single or double-stranded synthetic polyribonucleotides were degraded by the enzyme. The enzyme possesses a molecular weight of about 36,000 and requires alkaline pH, magnesium ions, and ammonium sulphate for maximum activity. The enzyme acts on the hybrid as an endonuclease, resulting in oligonucleotides with 3'-hydroxyl termini. The properties of this enzyme were distinct from those of the rat liver cytosol enzyme reported by Roewekamp and Sekeris in many respects, such as molecular weight, optimal pH and requirements for divalent cations. Preliminary experiments suggest that the nuclear enzyme is localized in the nucleoplasm and nucleoli. These results indicate that multiple forms of ribonuclease H exist in different regions of rat liver cells.", "contents": "Ribonuclease H from rat liver. I. Partial purification and characterization of nuclear ribonuclease H1. A ribonuclease H, an enzyme that specifically degrades the RNA moiety of RNA-DNA hybrid, has been partially purified from rat liver nuclei and characterized. Neither native or denatured DNA, nor single or double-stranded synthetic polyribonucleotides were degraded by the enzyme. The enzyme possesses a molecular weight of about 36,000 and requires alkaline pH, magnesium ions, and ammonium sulphate for maximum activity. The enzyme acts on the hybrid as an endonuclease, resulting in oligonucleotides with 3'-hydroxyl termini. The properties of this enzyme were distinct from those of the rat liver cytosol enzyme reported by Roewekamp and Sekeris in many respects, such as molecular weight, optimal pH and requirements for divalent cations. Preliminary experiments suggest that the nuclear enzyme is localized in the nucleoplasm and nucleoli. These results indicate that multiple forms of ribonuclease H exist in different regions of rat liver cells."}
{"id": "PMID:29890", "title": "Ribonuclease H from rat liver. II. Partial purification and characterization of cytosol ribonuclease H1.", "content": "We have detected in rat liver cytosol three enzymes (termed C-1, C-2, and C-3) which cleaved the RNA moiety of RNA-DNA hybrid. These enzymes were separated from each other by DEAE-Sephadex and Sephadex G-200 chromatography. C-1 and C-2 specifically act on the RNA moiety of RNA-DNA hybrid, while C-3 degrades single-stranded RNA as well as the RNA of the hybrid. The molecular weights of C-1, C-2, and C-3 are about 110,000, 35,000 and 110,000 daltons, respectively, and their activities are absolutely dependent on divalent cations such as Mg2+ and Mn2+. Cleavage by C-1 and C-2 is endonucleolytic, producing mostly oligonucleotides and a small amount of mononucleotides which possess 3'-hydroxyl termini. It seems likely that C-2 is originally present in the nucleus and is released into cytosol because of its loose binding to the nuclear components. As for biochemical properties, C-1 is very similar to the cytosol ribonuclease H initially reported by Roewekamp and Sekeris, and C-2 is very similar to the nuclear ribonuclease H reported by us in the preceding paper.", "contents": "Ribonuclease H from rat liver. II. Partial purification and characterization of cytosol ribonuclease H1. We have detected in rat liver cytosol three enzymes (termed C-1, C-2, and C-3) which cleaved the RNA moiety of RNA-DNA hybrid. These enzymes were separated from each other by DEAE-Sephadex and Sephadex G-200 chromatography. C-1 and C-2 specifically act on the RNA moiety of RNA-DNA hybrid, while C-3 degrades single-stranded RNA as well as the RNA of the hybrid. The molecular weights of C-1, C-2, and C-3 are about 110,000, 35,000 and 110,000 daltons, respectively, and their activities are absolutely dependent on divalent cations such as Mg2+ and Mn2+. Cleavage by C-1 and C-2 is endonucleolytic, producing mostly oligonucleotides and a small amount of mononucleotides which possess 3'-hydroxyl termini. It seems likely that C-2 is originally present in the nucleus and is released into cytosol because of its loose binding to the nuclear components. As for biochemical properties, C-1 is very similar to the cytosol ribonuclease H initially reported by Roewekamp and Sekeris, and C-2 is very similar to the nuclear ribonuclease H reported by us in the preceding paper."}
{"id": "PMID:29891", "title": "Multiple attack in porcine pancreatic alpha-amylase-catalyzed hydrolysis of amylose studied with a fluorescence probe.", "content": "1. A large fluorescence enhancement of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) observed in the presence of amylose was utilized to monitor quantitatively the time course of porcine pancreatic alpha-amylase [EC 3.2.1.1] (PPA)-catalyzed hydrolysis of amylose with a number-average degree of polymerization of 16.8. 2. The slope of the plot of decrease in the relative fluorescence intensity of the TNS-amylose system (termed as the fluorescence value) versus the number of linkages hydrolyzed (reducing value) (Kondo, H. et al. (1977) Agric. Biol. Chem. 41, 631-634) in the course of PPA-catalyzed hydrolysis was shown to be useful to describe the degree of \"multiple attack,\" which is defined by the number of reattacks on a long chain substrate molecular per one encounter of the enzyme and the substrate. A parameter gamma was defined as the ratio of the reciprocal of the slopes obtained at each pH to that at pH 10.5, where the multiple attack is not operating. 3. The gamma versus pH profile gave an apparent pK value of about 9, indicating that some ionizable groups participate in the multiple attack mechanism. 4. Based on a reaction scheme involving a \"sliding\" of the substrate molecule on the enzyme, which may contribute to the multiple attack mechanism, besides binding, dissociation, and cleavage steps of the substrate, and on the assumption of the steady state for the enzyme-substrate complex, rate equations were obtained to describe the time course of hydrolysis of a linear substrate. The product distribution with the progress of the reaction can be calculated theoretically, and is dependent on the number of multiple attack and the mode of sliding. The number of multiple attack can be estimated from this distribution, and the fluorescence value can be calculated theoretically by combining the product distribution with the relative efficiency of fluorescence intensity of each maltooligosaccharide (Nakatani, H. et. al. (1977) Biopolymers 16, 2363-2370). By comparing the experimental data with the theoretical ones, it was suggested that the multiple attack occurs through the sliding by maltose unit of the retained fragment on the enzyme, which is one of the fragments produced by the initial cleavage of the substrate molecule. 5. It was found that anions (chloride, bromide, and nitrate ions) which critically affect the enzyme activity have no effect on the degree of multiple attack.", "contents": "Multiple attack in porcine pancreatic alpha-amylase-catalyzed hydrolysis of amylose studied with a fluorescence probe. 1. A large fluorescence enhancement of 2-p-toluidinylnaphthalene-6-sulfonate (TNS) observed in the presence of amylose was utilized to monitor quantitatively the time course of porcine pancreatic alpha-amylase [EC 3.2.1.1] (PPA)-catalyzed hydrolysis of amylose with a number-average degree of polymerization of 16.8. 2. The slope of the plot of decrease in the relative fluorescence intensity of the TNS-amylose system (termed as the fluorescence value) versus the number of linkages hydrolyzed (reducing value) (Kondo, H. et al. (1977) Agric. Biol. Chem. 41, 631-634) in the course of PPA-catalyzed hydrolysis was shown to be useful to describe the degree of \"multiple attack,\" which is defined by the number of reattacks on a long chain substrate molecular per one encounter of the enzyme and the substrate. A parameter gamma was defined as the ratio of the reciprocal of the slopes obtained at each pH to that at pH 10.5, where the multiple attack is not operating. 3. The gamma versus pH profile gave an apparent pK value of about 9, indicating that some ionizable groups participate in the multiple attack mechanism. 4. Based on a reaction scheme involving a \"sliding\" of the substrate molecule on the enzyme, which may contribute to the multiple attack mechanism, besides binding, dissociation, and cleavage steps of the substrate, and on the assumption of the steady state for the enzyme-substrate complex, rate equations were obtained to describe the time course of hydrolysis of a linear substrate. The product distribution with the progress of the reaction can be calculated theoretically, and is dependent on the number of multiple attack and the mode of sliding. The number of multiple attack can be estimated from this distribution, and the fluorescence value can be calculated theoretically by combining the product distribution with the relative efficiency of fluorescence intensity of each maltooligosaccharide (Nakatani, H. et. al. (1977) Biopolymers 16, 2363-2370). By comparing the experimental data with the theoretical ones, it was suggested that the multiple attack occurs through the sliding by maltose unit of the retained fragment on the enzyme, which is one of the fragments produced by the initial cleavage of the substrate molecule. 5. It was found that anions (chloride, bromide, and nitrate ions) which critically affect the enzyme activity have no effect on the degree of multiple attack."}
{"id": "PMID:29892", "title": "Subunit structure of islets-activating protein (IAP), a new protein isolated from the culture media of Bordetella pertussis.", "content": "The subunit structure was studied of islets-activating protein (IAP), a new protein recently isolated from the culture media of Bordetella pertussis and possessing a unique action, i.e., potentiating insulin secretory responses of animals, IAP dissociated into three subunits, F-1, F-2, and F-3, when incubated in 8M urea. Three subunits isolated by chromatography on CM-Sepharose and DEAE-Sepharose columns showed different molecular weights (F-1: 44,000, F-2: 20,000, F-3: 11,000) and different isoelectric points, but similar amino acid compositions. The F-1 subunit consisted of two polypeptide chains linked by S-S bonding(s), while the F-2 and F-3 subunits were single-chain peptides. These subunits, none of which was biologically active alone, associated upon incubation for 2 h at 37 degrees C and regained biological activities after association only when the F-3 subunit was present in the association product. Thus, the F-3 subunit was essential, and the F-1 and F-2 subunits were permissive, for the development of IAP activity in animals.", "contents": "Subunit structure of islets-activating protein (IAP), a new protein isolated from the culture media of Bordetella pertussis. The subunit structure was studied of islets-activating protein (IAP), a new protein recently isolated from the culture media of Bordetella pertussis and possessing a unique action, i.e., potentiating insulin secretory responses of animals, IAP dissociated into three subunits, F-1, F-2, and F-3, when incubated in 8M urea. Three subunits isolated by chromatography on CM-Sepharose and DEAE-Sepharose columns showed different molecular weights (F-1: 44,000, F-2: 20,000, F-3: 11,000) and different isoelectric points, but similar amino acid compositions. The F-1 subunit consisted of two polypeptide chains linked by S-S bonding(s), while the F-2 and F-3 subunits were single-chain peptides. These subunits, none of which was biologically active alone, associated upon incubation for 2 h at 37 degrees C and regained biological activities after association only when the F-3 subunit was present in the association product. Thus, the F-3 subunit was essential, and the F-1 and F-2 subunits were permissive, for the development of IAP activity in animals."}
{"id": "PMID:29893", "title": "Purification and characterization of L-pyrrolidonecarboxylate peptidase from Bacillus amyloiliquefaciens.", "content": "Microorganisms capable of producing L-pyrrolidonecarboxylate peptidase [L-pyrrolidonyl peptidase, EC 3.4.11.8] were screened and a strain of Bacillus amyloliquefaciens was chosen as one of the most potent producers of the enzyme. The enzyme was purified from lysozyme-lysate of the bacterial cells by salting out with ammonium sulfate, adsorption on DEAE-cellulose, covalent chromatography on PCMB-Sepharose and by gel filtration on Sephadex G-150. By these procedures, the enzyme was purified about 800-fold with an activity recovery of 9%, and the preparation was electrophoretically homogenous. The enzyme was most active and stable at pH 7-8. The presence of 2-mercaptoethanol and EDTA was effective for stabilizing the enzyme. The molecular weight was estimated to be 72,000 by the gel filtration method and to be 24,000 by SDS-polyacrylamide gel electrophoresis, suggesting that the enzyme is a subunit oligomer, presumably trimer. The enzyme was inactivated by the addition of PCMB, sodium tetrathionate, Hg2+ and Cu2+, but the activity lost was restored by the addition of 2-mercaptoethanol and EDTA. The purified enzyme split amide and ester linkages in L-pyroglutamyl derivatives of L-alanine, beta-naphthylamine, alpha-naphthol, and 4-methylumbelliferone, but was completely inert towards various peptides and esters used as substrates for usual amino- and carboxy-peptidases, and for endopeptidases such as trypsin, subtilisin and alpha-chymotrypsin.", "contents": "Purification and characterization of L-pyrrolidonecarboxylate peptidase from Bacillus amyloiliquefaciens. Microorganisms capable of producing L-pyrrolidonecarboxylate peptidase [L-pyrrolidonyl peptidase, EC 3.4.11.8] were screened and a strain of Bacillus amyloliquefaciens was chosen as one of the most potent producers of the enzyme. The enzyme was purified from lysozyme-lysate of the bacterial cells by salting out with ammonium sulfate, adsorption on DEAE-cellulose, covalent chromatography on PCMB-Sepharose and by gel filtration on Sephadex G-150. By these procedures, the enzyme was purified about 800-fold with an activity recovery of 9%, and the preparation was electrophoretically homogenous. The enzyme was most active and stable at pH 7-8. The presence of 2-mercaptoethanol and EDTA was effective for stabilizing the enzyme. The molecular weight was estimated to be 72,000 by the gel filtration method and to be 24,000 by SDS-polyacrylamide gel electrophoresis, suggesting that the enzyme is a subunit oligomer, presumably trimer. The enzyme was inactivated by the addition of PCMB, sodium tetrathionate, Hg2+ and Cu2+, but the activity lost was restored by the addition of 2-mercaptoethanol and EDTA. The purified enzyme split amide and ester linkages in L-pyroglutamyl derivatives of L-alanine, beta-naphthylamine, alpha-naphthol, and 4-methylumbelliferone, but was completely inert towards various peptides and esters used as substrates for usual amino- and carboxy-peptidases, and for endopeptidases such as trypsin, subtilisin and alpha-chymotrypsin."}
{"id": "PMID:29894", "title": "The stereochemical course of acetate activation by yeast acetyl-CoA synthetase.", "content": "The purified alpha-thiophosphate diastereoisomers of adenosine 5'-(1-thio)-triphosphate were used to study the stereochemical course of the reaction catalyzed by yeast acetyl-CoA synthetase. Asymmetrically labeled adenosine 5'-thiophosphate was formed from the \"B\" diastereoisomer of adenosine 5'-(1-thio)-triphosphate and [18O]acetate. The label was found to be in the opposite orientation from the leaving pyrophosphate group showing that the acetate activation step occurred with inversion of configuration at the alpha-phosphorus.", "contents": "The stereochemical course of acetate activation by yeast acetyl-CoA synthetase. The purified alpha-thiophosphate diastereoisomers of adenosine 5'-(1-thio)-triphosphate were used to study the stereochemical course of the reaction catalyzed by yeast acetyl-CoA synthetase. Asymmetrically labeled adenosine 5'-thiophosphate was formed from the \"B\" diastereoisomer of adenosine 5'-(1-thio)-triphosphate and [18O]acetate. The label was found to be in the opposite orientation from the leaving pyrophosphate group showing that the acetate activation step occurred with inversion of configuration at the alpha-phosphorus."}
{"id": "PMID:29895", "title": "The reversible binding of oxygen to sulfhemoglobin.", "content": "The O2 binding properties of sulfhemoglobin were studied. The oxygen tension required for half-saturation of sulfhemoglobin is more than 2 orders of magnitude higher than that for hemoglobin A. The binding of O2 exhibits an alkaline Bohr effect larger than that observed for hemoglobin, yet the Hill number is unity. From the Bohr titration curve, 0.68 proton is released during O2 binding at 0 degrees C. Sulfhemoglobin prepared from carboxypeptidase A-treated hemoglobin has an affinity for O2 which is about the same as that of sulfhemoglobin at the theoretical limit of the Bohr titration curve. Like its carboxypeptidase A-treated hemoglobin precursor, this sulfhemoglobin does not bind O2 cooperatively. Thus, sulfhemoglobin appears to be in a high affinity form at alkaline pH and a low affinity form at acid pH, similar to hemoglobin A. These results demonstrate that the magnitude of the Hill number is not always an indicator of the interaction between oxygen binding and other functions in a hemoglobin.", "contents": "The reversible binding of oxygen to sulfhemoglobin. The O2 binding properties of sulfhemoglobin were studied. The oxygen tension required for half-saturation of sulfhemoglobin is more than 2 orders of magnitude higher than that for hemoglobin A. The binding of O2 exhibits an alkaline Bohr effect larger than that observed for hemoglobin, yet the Hill number is unity. From the Bohr titration curve, 0.68 proton is released during O2 binding at 0 degrees C. Sulfhemoglobin prepared from carboxypeptidase A-treated hemoglobin has an affinity for O2 which is about the same as that of sulfhemoglobin at the theoretical limit of the Bohr titration curve. Like its carboxypeptidase A-treated hemoglobin precursor, this sulfhemoglobin does not bind O2 cooperatively. Thus, sulfhemoglobin appears to be in a high affinity form at alkaline pH and a low affinity form at acid pH, similar to hemoglobin A. These results demonstrate that the magnitude of the Hill number is not always an indicator of the interaction between oxygen binding and other functions in a hemoglobin."}
{"id": "PMID:29897", "title": "Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore.", "content": "Toxin II isolated from the sea anemone Anemonia sulcata enhances activation of the action potential sodium ionophore of electrically excitable neuroblastoma cells by veratridine and batrachotoxin. This heterotropic cooperative effect is identical to that observed previously with scorpion toxin but occurs at a 110-fold higher concentration. Depolarization of the neuroblastoma cells inhibits the effect of sea anemone toxin as observed previously for scorpion toxin. Specific scorpion toxin binding is inhibited by sea anemone toxin with KD approximately equal to 90 nM. These results show that the polypeptides scorpion toxin and sea anemone toxin II share a common receptors site associated with action potential sodium ionophores.", "contents": "Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore. Toxin II isolated from the sea anemone Anemonia sulcata enhances activation of the action potential sodium ionophore of electrically excitable neuroblastoma cells by veratridine and batrachotoxin. This heterotropic cooperative effect is identical to that observed previously with scorpion toxin but occurs at a 110-fold higher concentration. Depolarization of the neuroblastoma cells inhibits the effect of sea anemone toxin as observed previously for scorpion toxin. Specific scorpion toxin binding is inhibited by sea anemone toxin with KD approximately equal to 90 nM. These results show that the polypeptides scorpion toxin and sea anemone toxin II share a common receptors site associated with action potential sodium ionophores."}
{"id": "PMID:29898", "title": "Crystallographic studies on D-amino acid oxidase.", "content": "D-amino acid oxidase, a flavoprotein from hog kidneys, has been crystalized in two different forms. Orthorhombic prisms have been obtained from the enzyme.benzoate complex at pH 8.3; the space group is C2221 and the cell dimensions are a = 325A, b = 138.8 A, c = 200 A. At lower pH values, the enzyme crystallizes in trigonal prisms with a = b = 116.0 A, c = 399 A, space group P3112 or its enantiomorph. The two crystal forms have been obtained at 28 degrees C while at 4 degrees C only weak evidence of crystallization has been detected. In both crystalline modifications, the protein is highly associated.", "contents": "Crystallographic studies on D-amino acid oxidase. D-amino acid oxidase, a flavoprotein from hog kidneys, has been crystalized in two different forms. Orthorhombic prisms have been obtained from the enzyme.benzoate complex at pH 8.3; the space group is C2221 and the cell dimensions are a = 325A, b = 138.8 A, c = 200 A. At lower pH values, the enzyme crystallizes in trigonal prisms with a = b = 116.0 A, c = 399 A, space group P3112 or its enantiomorph. The two crystal forms have been obtained at 28 degrees C while at 4 degrees C only weak evidence of crystallization has been detected. In both crystalline modifications, the protein is highly associated."}
{"id": "PMID:29900", "title": "Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides.", "content": "Purified prostaglandin endoperoxides (PGG2 and PGH2) and hydroperoxides (15-OOH-PGE2) as well as fatty acid hydroperoxides (12-OOH-20:4, 15-00H-20:4, and 13-OOH-18:2) were examined as effectors of soluble splenic cell guanylate cyclase activity. The procedures described (in the miniprint supplement) for the preparation, purification, and characterization of these components circumvented the use of diethyl ether which obscured effects of lipid effectors because of contaminants presumed to be ether peroxides which were stimulatory to the cyclase. Addition of prostaglandin endoperoxides or fatty acid hydroperoxides to the reaction mixture led to a time-dependent activation of guanylate cyclase activity; 2.5- to 5-fold stimulation was seen during the first 6 min. The degree of stimulation and rate of activation were dependent on the concentration of the fatty acid effector; when initial velocities (6 min) were assessed half-maximal stimulation was achieved in the range of 2 to 3 micrometer. However, by extending the incubation time to 90 min similar maximal increases in specific activity could be achieved with 3 or 10 micrometer PGG2 or PGH2. Activation of guanylate cyclase upon addition of prostaglandin endoperoxides or fatty acid hydroperoxides was prevented or reversed by the thiol reductants dithiothreitol (3 to 5 mM) or glutathione (10 to 15 mM). Na2S2O4, not known as an effective reducing agent of disulfides, prevented but was relatively ineffective in reversing activation after it had been induced by PGG2. Pretreatment of the enzyme preparation with increasing concentrations of N-ethylmaleimide in the range of 0.01 to 1.0 mM prevented activation by PGG2 without affecting basal guanylate cyclase activity. These observations indicate that fatty acid hydroperoxides and prostaglandin endoperoxides promote activation of the cyclase by oxidation of enzyme-related thiol functions. In contrast PGE2, PGF2a, hydroxy fatty acids (13-OH-18:2, 12-OH-20:4) as well as saturated (18:0) monoenoic (18:1), dienoic (18:2), and tetraenoic (20:4) fatty acids were ineffective in promoting cyclase activation in the range of 1 to 10 micrometer. Studies to identify the species of the rapidly metabolized prostaglandin endoperoxides that serve as effectors of the cyclase indicated that PGG2 but not 15-OOH-PGE2 (the major buffer-rearrangement product of PGG2) is most likely an activator. In the case of PGH2, a rapidly generated (30 s) metabolite of PGH2 was found which contained a hydroperoxy or endoperoxy functional group and was equally as effective as PGH2 as an apparent activator of the enzyme. The combined effects of PGG2 and dehydroascorbic acid, another class of activator, exhibited additivity with respect to the rate at which the time-dependent activation was induced. These results suggest that activation of soluble guanylate cyclase from splenic cells can be achieved by the oxidation of sulfhydryl groups that may be associated with specific hydrophobic sites of the enzyme or a related regulatory component.", "contents": "Activation of soluble splenic cell guanylate cyclase by prostaglandin endoperoxides and fatty acid hydroperoxides. Purified prostaglandin endoperoxides (PGG2 and PGH2) and hydroperoxides (15-OOH-PGE2) as well as fatty acid hydroperoxides (12-OOH-20:4, 15-00H-20:4, and 13-OOH-18:2) were examined as effectors of soluble splenic cell guanylate cyclase activity. The procedures described (in the miniprint supplement) for the preparation, purification, and characterization of these components circumvented the use of diethyl ether which obscured effects of lipid effectors because of contaminants presumed to be ether peroxides which were stimulatory to the cyclase. Addition of prostaglandin endoperoxides or fatty acid hydroperoxides to the reaction mixture led to a time-dependent activation of guanylate cyclase activity; 2.5- to 5-fold stimulation was seen during the first 6 min. The degree of stimulation and rate of activation were dependent on the concentration of the fatty acid effector; when initial velocities (6 min) were assessed half-maximal stimulation was achieved in the range of 2 to 3 micrometer. However, by extending the incubation time to 90 min similar maximal increases in specific activity could be achieved with 3 or 10 micrometer PGG2 or PGH2. Activation of guanylate cyclase upon addition of prostaglandin endoperoxides or fatty acid hydroperoxides was prevented or reversed by the thiol reductants dithiothreitol (3 to 5 mM) or glutathione (10 to 15 mM). Na2S2O4, not known as an effective reducing agent of disulfides, prevented but was relatively ineffective in reversing activation after it had been induced by PGG2. Pretreatment of the enzyme preparation with increasing concentrations of N-ethylmaleimide in the range of 0.01 to 1.0 mM prevented activation by PGG2 without affecting basal guanylate cyclase activity. These observations indicate that fatty acid hydroperoxides and prostaglandin endoperoxides promote activation of the cyclase by oxidation of enzyme-related thiol functions. In contrast PGE2, PGF2a, hydroxy fatty acids (13-OH-18:2, 12-OH-20:4) as well as saturated (18:0) monoenoic (18:1), dienoic (18:2), and tetraenoic (20:4) fatty acids were ineffective in promoting cyclase activation in the range of 1 to 10 micrometer. Studies to identify the species of the rapidly metabolized prostaglandin endoperoxides that serve as effectors of the cyclase indicated that PGG2 but not 15-OOH-PGE2 (the major buffer-rearrangement product of PGG2) is most likely an activator. In the case of PGH2, a rapidly generated (30 s) metabolite of PGH2 was found which contained a hydroperoxy or endoperoxy functional group and was equally as effective as PGH2 as an apparent activator of the enzyme. The combined effects of PGG2 and dehydroascorbic acid, another class of activator, exhibited additivity with respect to the rate at which the time-dependent activation was induced. These results suggest that activation of soluble guanylate cyclase from splenic cells can be achieved by the oxidation of sulfhydryl groups that may be associated with specific hydrophobic sites of the enzyme or a related regulatory component."}
{"id": "PMID:29902", "title": "Biochemical studies of isolated glial (M\u00fcller) cells from the turtle retina.", "content": "A method has been developed for the preparation of large numbers of glial (Muller) cells from the turtle retina. After proteolytic dissociation of the retina, Muller cells were separated from retinal neurons by velocity sedimentation at unit gravity. Fractions containing >90 percent morphologically identifiable Muller cells were prepared by this procedure. Fractions containing only Muller cells were obtained by drawing selected cells individually into a micropipette under visual observation. Biochemical analyses of isolated Muller cells showed that (a) these cells did not synthesize and accumulate acetylcholine, gamma-aminobutyric acid, or catecholamines when incubated with appropriate radioactive precursors; (b) the specific activities of choline acetyltransferase (EC 2.3.1.6), glutamate decarboxylase (EC 4.1.1.15), and tyrosine hydroxylase (EC 1.14.16.2) in these cells were less than 2 percent of those found in the retina; (c) Muller cells, however, contained high activities of transmitter degrading enzymes-acetylcholinesterase (EC 3.1.1.7) and gamma-aminobutyrate- transamine (EC 2.6.1.19); and (d) the cells also possessed high levels of two presumably glial-specific-enzymes-glutamine synthetase (EC 6.3.1.2) and carbonic anhydrase (EC 4.2.1.1). These results, together with other findings, suggest that Muller cells are not capable of neurotransmitter syntheses but possess the enzymes necessary for two important roles in the retina: (a) the inactivation of certain transmitters after synaptic transmission by uptake and degradation, and (b) the maintenance of acid-base balance and the provision of a stable microenvironment in the retina by the removal of metabolic products such as carbon dioxide and ammonia.", "contents": "Biochemical studies of isolated glial (M\u00fcller) cells from the turtle retina. A method has been developed for the preparation of large numbers of glial (Muller) cells from the turtle retina. After proteolytic dissociation of the retina, Muller cells were separated from retinal neurons by velocity sedimentation at unit gravity. Fractions containing >90 percent morphologically identifiable Muller cells were prepared by this procedure. Fractions containing only Muller cells were obtained by drawing selected cells individually into a micropipette under visual observation. Biochemical analyses of isolated Muller cells showed that (a) these cells did not synthesize and accumulate acetylcholine, gamma-aminobutyric acid, or catecholamines when incubated with appropriate radioactive precursors; (b) the specific activities of choline acetyltransferase (EC 2.3.1.6), glutamate decarboxylase (EC 4.1.1.15), and tyrosine hydroxylase (EC 1.14.16.2) in these cells were less than 2 percent of those found in the retina; (c) Muller cells, however, contained high activities of transmitter degrading enzymes-acetylcholinesterase (EC 3.1.1.7) and gamma-aminobutyrate- transamine (EC 2.6.1.19); and (d) the cells also possessed high levels of two presumably glial-specific-enzymes-glutamine synthetase (EC 6.3.1.2) and carbonic anhydrase (EC 4.2.1.1). These results, together with other findings, suggest that Muller cells are not capable of neurotransmitter syntheses but possess the enzymes necessary for two important roles in the retina: (a) the inactivation of certain transmitters after synaptic transmission by uptake and degradation, and (b) the maintenance of acid-base balance and the provision of a stable microenvironment in the retina by the removal of metabolic products such as carbon dioxide and ammonia."}
{"id": "PMID:29903", "title": "Unusual responses of rat hepatic and renal peroxisomes to RMI 14, 514, a new hypolipidemic agent.", "content": "RMI 14, 514 ([5-tetradecycloxy]-2-furancarboxylic acid) represents a new class of hypolipidemic agents which cause unusual ultrastructural changes in liver of male rats and in selected peroxisomal enzymes in liver and kidney of both sexes. Among the principal ultrastructural changes in peroxisomes of male rat liver were (a) cavitation and compartmentalization of the matrix, often giving the appearance of a peroxisome-within-a-peroxisome, and (b) narrow, dense extensions of canaliculi or cisterns from the  periphery of the peroxisome, forming partial circlets or surrounding irregular areas of cytoplasm. The unusual enzyme responses were (a) elevation of catalase activity in liver and kidney in female rats, (b) increased activity of three hydrogen peroxide-producing oxidases (urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase) in the liver of both sexes, and (c) elevation of activity of the last two oxidases in male kidney. The peculiar ultrastructural changes in liver peroxisomes combined with the responses of selected peroxisomal enzymes represent unusual modulations or adaptations of these organelles to a hypolipidemic agent, the effects of which have not been reported extensively.", "contents": "Unusual responses of rat hepatic and renal peroxisomes to RMI 14, 514, a new hypolipidemic agent. RMI 14, 514 ([5-tetradecycloxy]-2-furancarboxylic acid) represents a new class of hypolipidemic agents which cause unusual ultrastructural changes in liver of male rats and in selected peroxisomal enzymes in liver and kidney of both sexes. Among the principal ultrastructural changes in peroxisomes of male rat liver were (a) cavitation and compartmentalization of the matrix, often giving the appearance of a peroxisome-within-a-peroxisome, and (b) narrow, dense extensions of canaliculi or cisterns from the  periphery of the peroxisome, forming partial circlets or surrounding irregular areas of cytoplasm. The unusual enzyme responses were (a) elevation of catalase activity in liver and kidney in female rats, (b) increased activity of three hydrogen peroxide-producing oxidases (urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase) in the liver of both sexes, and (c) elevation of activity of the last two oxidases in male kidney. The peculiar ultrastructural changes in liver peroxisomes combined with the responses of selected peroxisomal enzymes represent unusual modulations or adaptations of these organelles to a hypolipidemic agent, the effects of which have not been reported extensively."}
{"id": "PMID:29904", "title": "Aspects of turnover and biogenesis of synaptic vesicles at locust neuromuscular junctions as revealed by zinc iodide-osmium tetroxide (ZIO) reacting with intravesicular SH-groups.", "content": "Retractor unguis nerve muscle preparations from the locust were subjected to the zinc iodide-osmium tetroxide reaction (ZIO) after pre-fixation in glutaraldehyde. Applied for 18 h at 4 degrees C in the dark, ZIO reacts at pH 4.2--4.0 fairly selectively with the matrix of synaptic vesicles. Approximately 53% of the vesicles are completely and 4% partially stained. The percentage of ZIO-positive vesicles is increased to nearly 90% and reduced to 4% or less by pretreatment with SH-protecting (dithiothreitol) or SH-blocking (N-ethylmaleimide, p-chloromercuriphenyl sulfonic acid) and SH-oxidizing (azodicarboxylic acid-bis-dimethylamide) reagents, respectively. Stimulation of the motor nerve at 20 Hz for 7 min, partially fatiguing synaptic transmission, reduces the number of vesicles per square micrometer of terminal area by approximately 52%; 2 min of rest restores this number of its pre-stimulation level. These changes are chiefly accounted for by changes in the number of completely ZIO-positive vesicles. 2 min after the end of stimulation, partially ZIO-positive vesicles are three times more frequent than before. With all experimental conditions, the average volume of vesicles was as follows: ZIO-negative less than partially ZIO-positive less than completely ZIO-positive. The average volume of ZIO-positive vesicles is almost unaffected by stimulation; that of ZIO-negative vesicles is decreased by 25% immediately after stimulation, increasing with subsequent rest to the initial level after 1 h. It is suggested (a) that ZIO demonstrates intravesicular protein(s) containing SH-groups and (b) that the completely ZIO-positive vesicles represent the mature ones ready to be used for transmitter release. How the ZIO reaction differentiates between different developmental stages of vesicles which could arise from the smooth endoplasmic reticulum is discussed.", "contents": "Aspects of turnover and biogenesis of synaptic vesicles at locust neuromuscular junctions as revealed by zinc iodide-osmium tetroxide (ZIO) reacting with intravesicular SH-groups. Retractor unguis nerve muscle preparations from the locust were subjected to the zinc iodide-osmium tetroxide reaction (ZIO) after pre-fixation in glutaraldehyde. Applied for 18 h at 4 degrees C in the dark, ZIO reacts at pH 4.2--4.0 fairly selectively with the matrix of synaptic vesicles. Approximately 53% of the vesicles are completely and 4% partially stained. The percentage of ZIO-positive vesicles is increased to nearly 90% and reduced to 4% or less by pretreatment with SH-protecting (dithiothreitol) or SH-blocking (N-ethylmaleimide, p-chloromercuriphenyl sulfonic acid) and SH-oxidizing (azodicarboxylic acid-bis-dimethylamide) reagents, respectively. Stimulation of the motor nerve at 20 Hz for 7 min, partially fatiguing synaptic transmission, reduces the number of vesicles per square micrometer of terminal area by approximately 52%; 2 min of rest restores this number of its pre-stimulation level. These changes are chiefly accounted for by changes in the number of completely ZIO-positive vesicles. 2 min after the end of stimulation, partially ZIO-positive vesicles are three times more frequent than before. With all experimental conditions, the average volume of vesicles was as follows: ZIO-negative less than partially ZIO-positive less than completely ZIO-positive. The average volume of ZIO-positive vesicles is almost unaffected by stimulation; that of ZIO-negative vesicles is decreased by 25% immediately after stimulation, increasing with subsequent rest to the initial level after 1 h. It is suggested (a) that ZIO demonstrates intravesicular protein(s) containing SH-groups and (b) that the completely ZIO-positive vesicles represent the mature ones ready to be used for transmitter release. How the ZIO reaction differentiates between different developmental stages of vesicles which could arise from the smooth endoplasmic reticulum is discussed."}
{"id": "PMID:29905", "title": "Ionic interactions between bovine chymotrypsinogen A and chondroitin sulfate A.B.C.. A possible model for molecular aggregation in zymogen granules.", "content": "The formation of large aggregates by ionic interactions between acidic glucosaminoglycans and cationic secretory proteins has been proposed as one of the critical steps in the concentration process in the condensing vacuoles of secretory cells. In this paper, this hypothesis was tested by studies on the interactions between bovine chymotrypsinogen A and chondroitin sulfate as a simplified model. Small amounts of chondroitin sulfate were found able to induce chymotrypsinogen precipitation. Like zymogen granules, the resulting aggregates were moderately sensitive to ionic strength and insensitive to osmolality. Moreover, their pH dependence was similar to that of isolated zymogen granules. When sulfated glucosaminoglycans isolated from the zymogen granules of the guinea pig pancreas were used instead of chondroitin sulfate, the same kind of interactions with chymotrypsinogen were obtained. Our data support the hypothesis that the strong ionic interactions between those sulfated glucosaminoglycans and cationic proteins could be responsible for the concentration process.", "contents": "Ionic interactions between bovine chymotrypsinogen A and chondroitin sulfate A.B.C.. A possible model for molecular aggregation in zymogen granules. The formation of large aggregates by ionic interactions between acidic glucosaminoglycans and cationic secretory proteins has been proposed as one of the critical steps in the concentration process in the condensing vacuoles of secretory cells. In this paper, this hypothesis was tested by studies on the interactions between bovine chymotrypsinogen A and chondroitin sulfate as a simplified model. Small amounts of chondroitin sulfate were found able to induce chymotrypsinogen precipitation. Like zymogen granules, the resulting aggregates were moderately sensitive to ionic strength and insensitive to osmolality. Moreover, their pH dependence was similar to that of isolated zymogen granules. When sulfated glucosaminoglycans isolated from the zymogen granules of the guinea pig pancreas were used instead of chondroitin sulfate, the same kind of interactions with chymotrypsinogen were obtained. Our data support the hypothesis that the strong ionic interactions between those sulfated glucosaminoglycans and cationic proteins could be responsible for the concentration process."}
{"id": "PMID:29906", "title": "Red cell aging. II. Anomalous electrophoretic properties of neuraminidase treated human erythrocytes.", "content": "Desialylation of human red blood cells (RBC) by Vibrio cholerae neuraminidase (VCN) was found to produce cells with electrophoretic properties which were inconsistent with the view of simple loss of N-acetylneuraminic acid (NANA) as the sole effect of VCN treatment. Modification of human RBC with 50--350 U VCN/10(10) RBC for one hour at 37 degrees C releases 90-100% of the NANA and produces a progressive decrease towards zero in their electrophoretic mobilities when measured in 0.15 M NaCl (pH 7.2) at 25 degrees C. The appearance of positive groups on the desialylated cells was indicated by the VCN-treated cells displaying positive mobilities below approximately pH 5.5 and increased negative mobilities at approximately pH 9 as well as substantial increases in their mobility at neutral pH following treatment with formaldehyde. Adsorption of about 95% of the VCN activity at 0 degrees C to the RBC did not produce any significant change in their electrophoretic mobilities thus indicating that the observed changes in the electrophoretic properties of the RBC following VCN treatment could not be attributable to adsorption of VCN. These studies indicate that the cationic charge groups which appear at the electrophoretic surface of the RBC after VCN treatment are probably of endogenous origin. It is suggested that this alteration rather than simple NANA release may operate to shorten the in vivo survival time of desialylated red cells.", "contents": "Red cell aging. II. Anomalous electrophoretic properties of neuraminidase treated human erythrocytes. Desialylation of human red blood cells (RBC) by Vibrio cholerae neuraminidase (VCN) was found to produce cells with electrophoretic properties which were inconsistent with the view of simple loss of N-acetylneuraminic acid (NANA) as the sole effect of VCN treatment. Modification of human RBC with 50--350 U VCN/10(10) RBC for one hour at 37 degrees C releases 90-100% of the NANA and produces a progressive decrease towards zero in their electrophoretic mobilities when measured in 0.15 M NaCl (pH 7.2) at 25 degrees C. The appearance of positive groups on the desialylated cells was indicated by the VCN-treated cells displaying positive mobilities below approximately pH 5.5 and increased negative mobilities at approximately pH 9 as well as substantial increases in their mobility at neutral pH following treatment with formaldehyde. Adsorption of about 95% of the VCN activity at 0 degrees C to the RBC did not produce any significant change in their electrophoretic mobilities thus indicating that the observed changes in the electrophoretic properties of the RBC following VCN treatment could not be attributable to adsorption of VCN. These studies indicate that the cationic charge groups which appear at the electrophoretic surface of the RBC after VCN treatment are probably of endogenous origin. It is suggested that this alteration rather than simple NANA release may operate to shorten the in vivo survival time of desialylated red cells."}
{"id": "PMID:29907", "title": "Analysis of lorazepam and its glucuronide metabolite by electron-capture gas--liquid chromatography. Use in pharmacokinetic studies of lorazepam.", "content": "This paper describes a rapid and sensitive method for analysis of lorazepam and its glucuronide metabolite in plasma and urine following therapeutic doses of lorazepam in humans. After addition of the structurally related benzodiazepine derivative, oxazepam, as the internal standard, 1-ml samples of plasma or urine are extracted twice at neutral pH with benzene (containing 1.5% isoamyl alcohol). The combined extracts are evaporated to dryness, reconstituted, and subjected to gas chromatographic analysis using a 3% OV-17 column and an electron-capture detector. Lorazepam glucuronide in urine is similarly analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of lorazepam per ml of original sample, and the variability of identical samples is 5% or less. The applicability of the method to pharmacokinetic studies of lorazepam is demonstrated.", "contents": "Analysis of lorazepam and its glucuronide metabolite by electron-capture gas--liquid chromatography. Use in pharmacokinetic studies of lorazepam. This paper describes a rapid and sensitive method for analysis of lorazepam and its glucuronide metabolite in plasma and urine following therapeutic doses of lorazepam in humans. After addition of the structurally related benzodiazepine derivative, oxazepam, as the internal standard, 1-ml samples of plasma or urine are extracted twice at neutral pH with benzene (containing 1.5% isoamyl alcohol). The combined extracts are evaporated to dryness, reconstituted, and subjected to gas chromatographic analysis using a 3% OV-17 column and an electron-capture detector. Lorazepam glucuronide in urine is similarly analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of lorazepam per ml of original sample, and the variability of identical samples is 5% or less. The applicability of the method to pharmacokinetic studies of lorazepam is demonstrated."}
{"id": "PMID:29908", "title": "Isoelectric focusing of the phosphoprotein of rat-incisor dentin in ampholine and acid pH gradients. Evidence for carrier ampholyte-protein complexes.", "content": "Rat-incisor phosphoprotein (RIP) has been subjected to isoelectric focusing at 4 degrees in (a) an Ampholine pH gradient of 2.5-4 and (b) an acid pH gradient created by electrolysis of a system of acids and acidic ampholytes and covering the pH range 0.5-3.5. In the Ampholine gradient, the RIP unexpectedly formed several adjacent and strongly opalescent bands in the pH range 2.5-3.1. These bands, which migrated slowly toward the anode on prolonged focusing, are interpreted as being the result of an interaction between the amino groups of the Ampholine and the numerous phosphate groups of the protein. In the acid pH gradient, the RIP focused into one narrow zone corresponding to an isoelectric pH of 1.1 at 4 degrees. This value is consistent with the amino-acid composition and the phosphate content of the protein,", "contents": "Isoelectric focusing of the phosphoprotein of rat-incisor dentin in ampholine and acid pH gradients. Evidence for carrier ampholyte-protein complexes. Rat-incisor phosphoprotein (RIP) has been subjected to isoelectric focusing at 4 degrees in (a) an Ampholine pH gradient of 2.5-4 and (b) an acid pH gradient created by electrolysis of a system of acids and acidic ampholytes and covering the pH range 0.5-3.5. In the Ampholine gradient, the RIP unexpectedly formed several adjacent and strongly opalescent bands in the pH range 2.5-3.1. These bands, which migrated slowly toward the anode on prolonged focusing, are interpreted as being the result of an interaction between the amino groups of the Ampholine and the numerous phosphate groups of the protein. In the acid pH gradient, the RIP focused into one narrow zone corresponding to an isoelectric pH of 1.1 at 4 degrees. This value is consistent with the amino-acid composition and the phosphate content of the protein,"}
{"id": "PMID:29909", "title": "Preparation of prereduced anaerobically sterilized media and their use in cultivation of anaerobic bacteria.", "content": "Several modifications of the roll-tube method have made it simpler for routine use in the isolation and growth of anaerobic bacteria. These include use of a check valve for the production of prereduced anaerobically sterilized media; a Salvarsan tube under oxygen-free gas pressure for the dispensing of molten prereduced anaerobically sterilized agar medium; a Kelly infusion bottle with a graduated pipette side arm (also under gas pressure) for quantitative delivery of fluid prereduced anaerobically sterilized media; and screw-capped prescription bottles for the cultivation of anaerobes. Colonies of Bacteroides melaninogenicus were easily identified and counted by this method. Other anaerobic bacteria have also been cultivated successfully.", "contents": "Preparation of prereduced anaerobically sterilized media and their use in cultivation of anaerobic bacteria. Several modifications of the roll-tube method have made it simpler for routine use in the isolation and growth of anaerobic bacteria. These include use of a check valve for the production of prereduced anaerobically sterilized media; a Salvarsan tube under oxygen-free gas pressure for the dispensing of molten prereduced anaerobically sterilized agar medium; a Kelly infusion bottle with a graduated pipette side arm (also under gas pressure) for quantitative delivery of fluid prereduced anaerobically sterilized media; and screw-capped prescription bottles for the cultivation of anaerobes. Colonies of Bacteroides melaninogenicus were easily identified and counted by this method. Other anaerobic bacteria have also been cultivated successfully."}
{"id": "PMID:29910", "title": "Immunoelectrophoresis for detection of polysaccharides in immune complexes.", "content": "A procedure for detecting pneumococcal capsular polysaccharides in immune complexes is described. Separation of antigen from immune complexes is achieved by electrophoresis at 56 degrees C.", "contents": "Immunoelectrophoresis for detection of polysaccharides in immune complexes. A procedure for detecting pneumococcal capsular polysaccharides in immune complexes is described. Separation of antigen from immune complexes is achieved by electrophoresis at 56 degrees C."}
{"id": "PMID:29911", "title": "Primary isolation media for Legionnaires disease bacterium.", "content": "Yolk sac suspensions infected with the Legionnaires disease bacterium (LDB) were plated onto 17 different bacteriological agar media. The LDB grew only on Mueller-Hinton agar supplemented with 1% Iso Vitale X and 1% hemoglobin (MH-IH). This medium was subsequently analyzed to determine the components required to support growth of the LDB. L-Cysteine hydrochloride can replace the Iso Vitale X reagent, and soluble ferric pyrophosphate can replace hemoglobin. A new medium, F-G agar, was formulated incorporating these chemicals. Different cultures conditions (oxygen tension, temperature, and pH) were also evaluated. The LDB grew optimally at 35 degrees C under 2.5% CO2 on the F-G agar adjusted to pH 6.9. When infected tissues were inoculated onto both F-G agar and MH-IH, the F-G agar produced colonies of the LDB more rapidly and in greater numbers than did MH-IH.", "contents": "Primary isolation media for Legionnaires disease bacterium. Yolk sac suspensions infected with the Legionnaires disease bacterium (LDB) were plated onto 17 different bacteriological agar media. The LDB grew only on Mueller-Hinton agar supplemented with 1% Iso Vitale X and 1% hemoglobin (MH-IH). This medium was subsequently analyzed to determine the components required to support growth of the LDB. L-Cysteine hydrochloride can replace the Iso Vitale X reagent, and soluble ferric pyrophosphate can replace hemoglobin. A new medium, F-G agar, was formulated incorporating these chemicals. Different cultures conditions (oxygen tension, temperature, and pH) were also evaluated. The LDB grew optimally at 35 degrees C under 2.5% CO2 on the F-G agar adjusted to pH 6.9. When infected tissues were inoculated onto both F-G agar and MH-IH, the F-G agar produced colonies of the LDB more rapidly and in greater numbers than did MH-IH."}
{"id": "PMID:29912", "title": "The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets.", "content": "NH4+ caused a dose-related, rapid, and reversible inhibition of glucose-stimulated insulin release by isolated rat islets. It also inhibited glyceraldehyde-, Ba2+-, and sulfonylurea-stimulated insulun secretion. NH4+ failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, AD, and AMP, and the intracellular pH. NH4+ also failed to affect the ability of theophylline and cytochalasin B to augment glucose-induced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration of NADH and HADPH and a concomitant alteration of 86Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous of exogenous nutrients, may modulate ionophoretic processes in the islet cells and by doing so, affect the net uptake of Ca2+ and subsequent release of insulin.", "contents": "The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets. NH4+ caused a dose-related, rapid, and reversible inhibition of glucose-stimulated insulin release by isolated rat islets. It also inhibited glyceraldehyde-, Ba2+-, and sulfonylurea-stimulated insulun secretion. NH4+ failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, AD, and AMP, and the intracellular pH. NH4+ also failed to affect the ability of theophylline and cytochalasin B to augment glucose-induced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration of NADH and HADPH and a concomitant alteration of 86Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous of exogenous nutrients, may modulate ionophoretic processes in the islet cells and by doing so, affect the net uptake of Ca2+ and subsequent release of insulin."}
{"id": "PMID:29915", "title": "Reproduction and breeding of goats.", "content": "Reproduction and genetics of the goat are reviewed with a view of increasing their contribution to mankind. The goat contributes most in tropical regions (within 30 degrees of the equator). The most important product from the goat is milk with meat a close second. Other products are minor. Reproductive rate is a problem only with the Angora goat, but increased reproduction with any type of goat would contribute to improved efficiency. Also, a knowledge of the reproductive phenomenon is necessary for effective management. Genetic studies of goats are limited, but this should not limit improvement programs. Excellent genotypes for producing milk and fiber are available, but adaptation to tropical conditions is needed. Even within temperature regions, there is little evidence of progress in breeding for milk production. Little has been done on the development of the goat as a meat animal. Also, research on crossbreeding for milk or meat production is limited.", "contents": "Reproduction and breeding of goats. Reproduction and genetics of the goat are reviewed with a view of increasing their contribution to mankind. The goat contributes most in tropical regions (within 30 degrees of the equator). The most important product from the goat is milk with meat a close second. Other products are minor. Reproductive rate is a problem only with the Angora goat, but increased reproduction with any type of goat would contribute to improved efficiency. Also, a knowledge of the reproductive phenomenon is necessary for effective management. Genetic studies of goats are limited, but this should not limit improvement programs. Excellent genotypes for producing milk and fiber are available, but adaptation to tropical conditions is needed. Even within temperature regions, there is little evidence of progress in breeding for milk production. Little has been done on the development of the goat as a meat animal. Also, research on crossbreeding for milk or meat production is limited."}
{"id": "PMID:29919", "title": "Efficacy  of intravenous pretesting and antihistamine prophylaxis in radiocontrast media--sensitive patients.", "content": "Intravenous pretesting with radiocontrast media (RCM) was performed in 204 RCM-sensitive patients considered for repeat contrast radiography. Group 1 had vague histories of prior anaphylactoid reaction and negative pretests, and 2 of 41 (4.9%) had reactions upon contrast radiography. Groups 2 to 5 had definite histories of prior anaphylactoid reaction. Group 2 had the radiographic study cancelled: 18 of 21 (85.7%) had positive pretests. Group 3 had positive pretests and underwent contrast radiography, and 9 of 15 (60%) had reactions despite premedication. Group 4 (no premedication) and group 5 (diphenhydramine premedication) had negative pretests, but 11 of 53 (20.7%) and 3 of 71 (4.2%), respectively, developed reactions (p less than 0.001). The reaction frequency in group 3 (posivie pretest) of 12 of 18 (66.7%) was greater than that in groups 4 and 5 (negative pretest) combined (14 of 124 (11.3%), p less than 0.001). Intravenous pretesting identified a high-risk group and diphenhydramine premedication decreased the frequency of reaction in patients sensitive to radiocontrast media.", "contents": "Efficacy  of intravenous pretesting and antihistamine prophylaxis in radiocontrast media--sensitive patients. Intravenous pretesting with radiocontrast media (RCM) was performed in 204 RCM-sensitive patients considered for repeat contrast radiography. Group 1 had vague histories of prior anaphylactoid reaction and negative pretests, and 2 of 41 (4.9%) had reactions upon contrast radiography. Groups 2 to 5 had definite histories of prior anaphylactoid reaction. Group 2 had the radiographic study cancelled: 18 of 21 (85.7%) had positive pretests. Group 3 had positive pretests and underwent contrast radiography, and 9 of 15 (60%) had reactions despite premedication. Group 4 (no premedication) and group 5 (diphenhydramine premedication) had negative pretests, but 11 of 53 (20.7%) and 3 of 71 (4.2%), respectively, developed reactions (p less than 0.001). The reaction frequency in group 3 (posivie pretest) of 12 of 18 (66.7%) was greater than that in groups 4 and 5 (negative pretest) combined (14 of 124 (11.3%), p less than 0.001). Intravenous pretesting identified a high-risk group and diphenhydramine premedication decreased the frequency of reaction in patients sensitive to radiocontrast media."}
{"id": "PMID:29925", "title": "[Therapeutics basis of threatened abortions (author's transl)].", "content": "The diverse hormonal and vascular medications are studied in the way of their mechanism of action, of their efficiency and their side effects on the mother as well as on the fetus. Neither definite argument, nor important statistical study has been made after elimination of all genetics and chromosomic anomalies. beta-mimetic, alphablocking and progesterone medications are the most efficient and certainly the less dangerous for the fetus.", "contents": "[Therapeutics basis of threatened abortions (author's transl)]. The diverse hormonal and vascular medications are studied in the way of their mechanism of action, of their efficiency and their side effects on the mother as well as on the fetus. Neither definite argument, nor important statistical study has been made after elimination of all genetics and chromosomic anomalies. beta-mimetic, alphablocking and progesterone medications are the most efficient and certainly the less dangerous for the fetus."}
{"id": "PMID:29927", "title": "Frequencies of pneumococcal types causing serious infections in patients admitted to the Radcliffe Infirmary, Oxford, 1969-77.", "content": "During a 7 1/2 year period pneumococci were isolated from body fluids of 124 patients at the Radcliffe Infirmary, Oxford -72 with pneumonia, 26 with meningitis and 26 with other serious infections. Eighty-one (65%) of the patients were over 50, and 33 (27%) were over 70 years old. Of the 124 pneumococcal strains 104 (84%), including 23 (79%) of those from patients who died, belonged to types included in the vaccines successfully used in South Africa and in Papua New Guinea. The relative frequencies of types in the Oxford series and in a larger British series agreed closely with those found in a recent survey of 3644 bacteraemic pneumococcal infections in 10 American cities. Any polyvalent pneumococcal vaccine licensed for use in the United States is thus likely to be relevant to the situation in Britain.", "contents": "Frequencies of pneumococcal types causing serious infections in patients admitted to the Radcliffe Infirmary, Oxford, 1969-77. During a 7 1/2 year period pneumococci were isolated from body fluids of 124 patients at the Radcliffe Infirmary, Oxford -72 with pneumonia, 26 with meningitis and 26 with other serious infections. Eighty-one (65%) of the patients were over 50, and 33 (27%) were over 70 years old. Of the 124 pneumococcal strains 104 (84%), including 23 (79%) of those from patients who died, belonged to types included in the vaccines successfully used in South Africa and in Papua New Guinea. The relative frequencies of types in the Oxford series and in a larger British series agreed closely with those found in a recent survey of 3644 bacteraemic pneumococcal infections in 10 American cities. Any polyvalent pneumococcal vaccine licensed for use in the United States is thus likely to be relevant to the situation in Britain."}
{"id": "PMID:29928", "title": "Effect of splenectomy on the expression of regulatory T cell activity.", "content": "The effect of adult splenectomy on the expression of suppressor and amplifier T cell activity was examined with respect to the serum antibody response to Type III pneumococcal polysaccharide (SSS-III) by using a sensitive radioimmunoassay. Suppressor T cell activity, as measured by the degree of low-dose paralysis induced, was not impaired in the least by splenectomy; however, amplifier T cell activity was almost completely eliminated within 7 days after splenectomy. These findings indicate that suppressor T cell activity is not confined solely to the spleen, the major site of antibody synthesis after immunization with SSS-III, and that the spleen may be an important site for the generation and/or maintenance of amplifier T cell activity.", "contents": "Effect of splenectomy on the expression of regulatory T cell activity. The effect of adult splenectomy on the expression of suppressor and amplifier T cell activity was examined with respect to the serum antibody response to Type III pneumococcal polysaccharide (SSS-III) by using a sensitive radioimmunoassay. Suppressor T cell activity, as measured by the degree of low-dose paralysis induced, was not impaired in the least by splenectomy; however, amplifier T cell activity was almost completely eliminated within 7 days after splenectomy. These findings indicate that suppressor T cell activity is not confined solely to the spleen, the major site of antibody synthesis after immunization with SSS-III, and that the spleen may be an important site for the generation and/or maintenance of amplifier T cell activity."}
{"id": "PMID:29929", "title": "An immunoprecipitation-dissociation technique for large scale antibody purification and an antigen consumption electroimmunoassay for antibody quantitation. A model study with antibodies to pregnancy zone protein.", "content": "A simple immunoprecipitation--dissociation technique for large scale purification of antibodies is described, which comprises selective denaturation of the antigen and recovery of the antibody fraction by exclusion chromatography at low pH. Its use is illustrated by the purification of antibodies to pregnancy zone protein. A purification factor of about 60 was achieved. An antigen consumption electroimmunoassay was also developed which permits quantitative determination of the antigen binding activity of antibodies with a given specificity. The methods have general application.", "contents": "An immunoprecipitation-dissociation technique for large scale antibody purification and an antigen consumption electroimmunoassay for antibody quantitation. A model study with antibodies to pregnancy zone protein. A simple immunoprecipitation--dissociation technique for large scale purification of antibodies is described, which comprises selective denaturation of the antigen and recovery of the antibody fraction by exclusion chromatography at low pH. Its use is illustrated by the purification of antibodies to pregnancy zone protein. A purification factor of about 60 was achieved. An antigen consumption electroimmunoassay was also developed which permits quantitative determination of the antigen binding activity of antibodies with a given specificity. The methods have general application."}
{"id": "PMID:29930", "title": "Organic solvents and temperature effects on desorption from immunoadsorbents. DNP-BSA anti-DNP as a model.", "content": "Conditions for desorbing a DNP carrier from its immunoadsorbent were studied in various hydro-organic media at different pHs and temperatures, including the sub-zero range. It appeared that DNP--anti-DNP interaction is the result of a balance between various bonds and the best result (95% yield) was obtained in hydro-organic solvent at high pH and +30 degrees C.", "contents": "Organic solvents and temperature effects on desorption from immunoadsorbents. DNP-BSA anti-DNP as a model. Conditions for desorbing a DNP carrier from its immunoadsorbent were studied in various hydro-organic media at different pHs and temperatures, including the sub-zero range. It appeared that DNP--anti-DNP interaction is the result of a balance between various bonds and the best result (95% yield) was obtained in hydro-organic solvent at high pH and +30 degrees C."}
{"id": "PMID:29934", "title": "The effect of calcium and magnesium on the spontaneous release of transmitter at insect motor nerve terminals.", "content": "1. The effect of the extracellular calcium and magnesium concentrations and calcium ionophore, X-537A, on the frequency of miniature excitatory post-synaptic potentials (MEPSPs) was studied in cockroach leg muscle fibres. 2. The frequency of MEPSPs increased as the calcium concentration was increased from 0.1 to 10 mM. In the presence of 10 mM magnesium, however, raising the calcium concentration from 0.1 to 1 mM slightly depressed the frequency. In saline containing elevated potassium (20.8 mM), increasing the calcium concentration produced a much higher frequency than that in the normal potassium saline (10.8 mM) in the absence of magnesium. Raising the extracellular potassium concentration was without effect unless the bathing solution contained calcium. 3. The frequency of the miniature potentials was reduced as the magnesium concentration was raised from 0 to 10 mM, depending on the presence of calcium ions. On the contrary, a slightly increased frequency was observed in the low calcium saline as the magnesium concentration was raised from 1 to 10 mM. The reciprocal relationship between calcium and magnesium and the time course of the effect suggest that both ions act at the same surface sites in the presynaptic membrane. 4. X-537A elicited a transient increase in frequency followed by a fall of the frequency to a very low rate. Further application of the ionophore was without effect. The effect of X-537A on the spontaneous release of transmitter at the insect neuromuscular junction was comparable with that on the spontaneous acetylcholine release in vertebrate neuromuscular junctions.", "contents": "The effect of calcium and magnesium on the spontaneous release of transmitter at insect motor nerve terminals. 1. The effect of the extracellular calcium and magnesium concentrations and calcium ionophore, X-537A, on the frequency of miniature excitatory post-synaptic potentials (MEPSPs) was studied in cockroach leg muscle fibres. 2. The frequency of MEPSPs increased as the calcium concentration was increased from 0.1 to 10 mM. In the presence of 10 mM magnesium, however, raising the calcium concentration from 0.1 to 1 mM slightly depressed the frequency. In saline containing elevated potassium (20.8 mM), increasing the calcium concentration produced a much higher frequency than that in the normal potassium saline (10.8 mM) in the absence of magnesium. Raising the extracellular potassium concentration was without effect unless the bathing solution contained calcium. 3. The frequency of the miniature potentials was reduced as the magnesium concentration was raised from 0 to 10 mM, depending on the presence of calcium ions. On the contrary, a slightly increased frequency was observed in the low calcium saline as the magnesium concentration was raised from 1 to 10 mM. The reciprocal relationship between calcium and magnesium and the time course of the effect suggest that both ions act at the same surface sites in the presynaptic membrane. 4. X-537A elicited a transient increase in frequency followed by a fall of the frequency to a very low rate. Further application of the ionophore was without effect. The effect of X-537A on the spontaneous release of transmitter at the insect neuromuscular junction was comparable with that on the spontaneous acetylcholine release in vertebrate neuromuscular junctions."}
{"id": "PMID:29935", "title": "Secretion of lysosomal hydrolases by stimulated and nonstimulated macrophages.", "content": "Peritoneal macrophages were obtained from untreated mice and from mice treated with thioglycollate medium (TA), proteose peptone medium (PP), or a suspension of streptococcus A cell wall material (SA). The biochemical and secretory properties of these cells in long term cultures (up to 2 wk) were compared. TA-elicited macrophages contained more protein, lactate dehydrogenase, lysosomal hydrolases, and in particular, more plasminogen activator than the other cells studied. All types of macrophages studied were found to release considerable amounts of lysosomal hydrolases (beta-glucuronidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, and acid phosphatase) into the medium. Release was independent of phagocytosis and must, therefore, be regarded as true secretion. In both elicited and nonelicited macrophages, the rates of lysosomal enzyme secretion were virtually identical in the presence and in the absence of serum, and they were not enhanced by increasing serum concentrations. Lysosomal enzyme secretion in macrophages appears to depend on protein synthesis, since it was blocked by low concentrations of cycloheximide which neither affected cell viability nor lowered the intracellular enzyme levels. The amounts of lysosomal hydrolases secreted were highest in TA-elicited macrophages. The rates of secretion of PP- or SA-elicited and of nonelicited macrophages were about one-fourth of that of the TA-elicited cells. This difference, although significant, is much smaller than that observed for the secretion of plasminogen activator which was 20-50 times higher in TA-elicited cells. Acid glycosidases were also found in the peritoneal lavage media used for cell harvesting from both treated and nontreated mice. This indicates that active secretion of lysosomal hydrolases may be an in vivo property of the macrophage.", "contents": "Secretion of lysosomal hydrolases by stimulated and nonstimulated macrophages. Peritoneal macrophages were obtained from untreated mice and from mice treated with thioglycollate medium (TA), proteose peptone medium (PP), or a suspension of streptococcus A cell wall material (SA). The biochemical and secretory properties of these cells in long term cultures (up to 2 wk) were compared. TA-elicited macrophages contained more protein, lactate dehydrogenase, lysosomal hydrolases, and in particular, more plasminogen activator than the other cells studied. All types of macrophages studied were found to release considerable amounts of lysosomal hydrolases (beta-glucuronidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, and acid phosphatase) into the medium. Release was independent of phagocytosis and must, therefore, be regarded as true secretion. In both elicited and nonelicited macrophages, the rates of lysosomal enzyme secretion were virtually identical in the presence and in the absence of serum, and they were not enhanced by increasing serum concentrations. Lysosomal enzyme secretion in macrophages appears to depend on protein synthesis, since it was blocked by low concentrations of cycloheximide which neither affected cell viability nor lowered the intracellular enzyme levels. The amounts of lysosomal hydrolases secreted were highest in TA-elicited macrophages. The rates of secretion of PP- or SA-elicited and of nonelicited macrophages were about one-fourth of that of the TA-elicited cells. This difference, although significant, is much smaller than that observed for the secretion of plasminogen activator which was 20-50 times higher in TA-elicited cells. Acid glycosidases were also found in the peritoneal lavage media used for cell harvesting from both treated and nontreated mice. This indicates that active secretion of lysosomal hydrolases may be an in vivo property of the macrophage."}
{"id": "PMID:29936", "title": "T-lymphocyte heterogeneity in the rat: separation of functional subpopulations using a monoclonal antibody.", "content": "W3/25 antibody is the monoclonal product of a hybrid cell resulting from the fusion of a mouse myeloma cell line with spleen cells from a mouse immunized with rat thymocytes. Pure clones have been derived, and segregants free of parental myeloma chains have been isolated. Previous studies have shown that this antibody recognizes a subpopulation of T cells among rat thoracic duct lymphocytes. In the work reported here, three T-cell functions were assayed after separating rat thoracic duct lymphocytes on the fluorescence-activated cell sorter on the basis of labeling with W3/25 antibody. Two of the functional activities appeared to be completely segregated by this procedure. Thus, helper cell activity for an anti-hapten plaque-forming cell response was confined to the labeled population, whereas the allogeneic suppressive effect produced in a parental vector F1 adoptive transfer was mediated by cells in the unlabeled fraction. The third function, graft-versus-host activity, was almost entirely contained within the labeled subpopulation. It is concluded that the antigenic determinant recognized by the monoclonal antibody W3/25 is a differentiation marker for T-cell functional subpopulations.", "contents": "T-lymphocyte heterogeneity in the rat: separation of functional subpopulations using a monoclonal antibody. W3/25 antibody is the monoclonal product of a hybrid cell resulting from the fusion of a mouse myeloma cell line with spleen cells from a mouse immunized with rat thymocytes. Pure clones have been derived, and segregants free of parental myeloma chains have been isolated. Previous studies have shown that this antibody recognizes a subpopulation of T cells among rat thoracic duct lymphocytes. In the work reported here, three T-cell functions were assayed after separating rat thoracic duct lymphocytes on the fluorescence-activated cell sorter on the basis of labeling with W3/25 antibody. Two of the functional activities appeared to be completely segregated by this procedure. Thus, helper cell activity for an anti-hapten plaque-forming cell response was confined to the labeled population, whereas the allogeneic suppressive effect produced in a parental vector F1 adoptive transfer was mediated by cells in the unlabeled fraction. The third function, graft-versus-host activity, was almost entirely contained within the labeled subpopulation. It is concluded that the antigenic determinant recognized by the monoclonal antibody W3/25 is a differentiation marker for T-cell functional subpopulations."}
{"id": "PMID:29937", "title": "Demonstration of opsonic activity and in vivo protection against group B streptococci type III by Streptococcus pneumoniae type 14 antisera.", "content": "The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective.", "contents": "Demonstration of opsonic activity and in vivo protection against group B streptococci type III by Streptococcus pneumoniae type 14 antisera. The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective."}
{"id": "PMID:29938", "title": "In vitro studies on lymphocyte differentiation. I. Long term in vitro culture of cells giving rise to functional lymphocytes in irradiated mice.", "content": "In vitro cultures of mouse bone marrow cells, maintained for periods up to 7 wk, were shown to contain cells able to repopulate irradiated hosts with T and B lymphocytes. The lymphocytes were fully functional and there did not appear to be any gross restriction of their receptor repertoire. The cultured cells reconstituted irradiated semiallogenic hosts without evidence of graft-versus-host disease, suggesting that culture of donor marrow might be a useful preliminary to transplantation when tissue matching is incomplete.", "contents": "In vitro studies on lymphocyte differentiation. I. Long term in vitro culture of cells giving rise to functional lymphocytes in irradiated mice. In vitro cultures of mouse bone marrow cells, maintained for periods up to 7 wk, were shown to contain cells able to repopulate irradiated hosts with T and B lymphocytes. The lymphocytes were fully functional and there did not appear to be any gross restriction of their receptor repertoire. The cultured cells reconstituted irradiated semiallogenic hosts without evidence of graft-versus-host disease, suggesting that culture of donor marrow might be a useful preliminary to transplantation when tissue matching is incomplete."}
{"id": "PMID:29953", "title": "Fat digestion in the stomach of premature infants. I. Characteristics of lipase activity.", "content": "Lipolytic activity was studied in gastric aspirates of 13 premature infants of birth weight 1,050 to 1,786 gm. All infants received a diet of infant formula fed by gastric tube. Gastric aspirates were collected after irrigating the stomach with 2 to 5 ml sterile saline before regular feeding. Lipolytic activity, tested with doubly labeled 3H glyceryl-14 C tripalmitin substrate, was 55.6 +/- 11.7 n mol/min/ml (range 4.2 to 140). The lipolytic activity had a pH optimum of 5.4 and produced partial glycerides (mono and diglycerides), glycerol, and free fatty acids. Lipolysis was inhibited by bile salts. Our findings show that in premature infants, as in adults, digestion of dietary fat starts in the stomach. Since bile salt concentrations are low in premature infants, the amphiphilic reaction products formed (monoglyceride and FFA) could play a significant role in the stabilization of lipid emulsions.", "contents": "Fat digestion in the stomach of premature infants. I. Characteristics of lipase activity. Lipolytic activity was studied in gastric aspirates of 13 premature infants of birth weight 1,050 to 1,786 gm. All infants received a diet of infant formula fed by gastric tube. Gastric aspirates were collected after irrigating the stomach with 2 to 5 ml sterile saline before regular feeding. Lipolytic activity, tested with doubly labeled 3H glyceryl-14 C tripalmitin substrate, was 55.6 +/- 11.7 n mol/min/ml (range 4.2 to 140). The lipolytic activity had a pH optimum of 5.4 and produced partial glycerides (mono and diglycerides), glycerol, and free fatty acids. Lipolysis was inhibited by bile salts. Our findings show that in premature infants, as in adults, digestion of dietary fat starts in the stomach. Since bile salt concentrations are low in premature infants, the amphiphilic reaction products formed (monoglyceride and FFA) could play a significant role in the stabilization of lipid emulsions."}
{"id": "PMID:29954", "title": "Pharmacokinetics of flunitrazepam following single- and multiple-dose oral administration to healthy human subjects.", "content": "Healthy human subjects received single and multiple oral doses of flunitrazepam. Absorption and disposition were first order and reproducible from administration. The oral doses were virtually completely available to the liver, and elimination from the body occurred entirely via metabolism. Assuming the liver to be the sole eliminating organ, hepatic blood clearance and extraction ratio were approximately 0.235 liter/hr/kg and 0.154, respectively. Steady-state blood volume of distribution averaged 3.76 liters/kg in the single-dose studies. Terminal exponential half-lives from the single- and multiple-dose studies (different subjects) averaged 13.5 and 19.2 hr, respectively; these differences were not due to clearance changes but were entirely attributable to variations in volumes of distribution.", "contents": "Pharmacokinetics of flunitrazepam following single- and multiple-dose oral administration to healthy human subjects. Healthy human subjects received single and multiple oral doses of flunitrazepam. Absorption and disposition were first order and reproducible from administration. The oral doses were virtually completely available to the liver, and elimination from the body occurred entirely via metabolism. Assuming the liver to be the sole eliminating organ, hepatic blood clearance and extraction ratio were approximately 0.235 liter/hr/kg and 0.154, respectively. Steady-state blood volume of distribution averaged 3.76 liters/kg in the single-dose studies. Terminal exponential half-lives from the single- and multiple-dose studies (different subjects) averaged 13.5 and 19.2 hr, respectively; these differences were not due to clearance changes but were entirely attributable to variations in volumes of distribution."}
{"id": "PMID:29955", "title": "Instability of digoxin in acid medium using a nonisotopic method.", "content": "A selective nonisotopic assay was used to investigate the digoxin hydrolysis rates at 37 +/- 0.1 degrees over the pH 1.1--2.2 range. The colorimetric method adopted is based on the use of a xanthydrol reagent after extraction with chloroform. The spectrofluorometric method specified in the dissolution test for digoxin tablets was nonspecific because of digoxigenin interference. Digoxin hydrolysis followed specific acid hydrolysis, and K values of the apparent first-order reaction varied from 0.0357 to 0.0027 min-1 over the pH range used. The effect of the dissolution medium on digoxin stability during the dissolution tests of the tablets also was studied. Water (the BP medium) and 0.6% HCl (the USP medium) were compared using the fluorometric method and the xanthydrol method. In the USP medium (pH 1.3), no hydrolysis was revealed by the fluorometric estimation whereas the xanthydrol method showed about 74% hydrolysis. In water, the two methods revealed no hydrolysis. The extent of hydrolysis after 1 hr in the USP medium was studied using three brands of digoxin tablets of differing dissolution characteristics. The fast dissolving brand showed relatively more hydrolysis than the slow dissolving tablets.", "contents": "Instability of digoxin in acid medium using a nonisotopic method. A selective nonisotopic assay was used to investigate the digoxin hydrolysis rates at 37 +/- 0.1 degrees over the pH 1.1--2.2 range. The colorimetric method adopted is based on the use of a xanthydrol reagent after extraction with chloroform. The spectrofluorometric method specified in the dissolution test for digoxin tablets was nonspecific because of digoxigenin interference. Digoxin hydrolysis followed specific acid hydrolysis, and K values of the apparent first-order reaction varied from 0.0357 to 0.0027 min-1 over the pH range used. The effect of the dissolution medium on digoxin stability during the dissolution tests of the tablets also was studied. Water (the BP medium) and 0.6% HCl (the USP medium) were compared using the fluorometric method and the xanthydrol method. In the USP medium (pH 1.3), no hydrolysis was revealed by the fluorometric estimation whereas the xanthydrol method showed about 74% hydrolysis. In water, the two methods revealed no hydrolysis. The extent of hydrolysis after 1 hr in the USP medium was studied using three brands of digoxin tablets of differing dissolution characteristics. The fast dissolving brand showed relatively more hydrolysis than the slow dissolving tablets."}
{"id": "PMID:29956", "title": "Ditheophylline succinate: transfer of theophylline across everted rat intestinal sacs.", "content": "The cumulative theophylline transfer rate across 10-cm everted rat intestinal sacs incubated at 37 degrees in pH 7.4 Krebs phosphate buffer was determined. A suspension of ditheophylline succinate ( a potential prodrug of theophylline) and a solution of theophylline at equimolar concentration were evaluated to determine the magnitude of the difference between the cumulative theophylline transfer rates from the two preparations. A linear concentration dependency for the rate across the intestinal wall was evidenced. The theophylline formation rate from ditheophylline succinate suspended in pH 7.4 Krebs buffer at 37 degrees followed apparent zero-order kinetics. The observed difference (fourfold) between the cumulative transfer rates estimated for the theophylline solution and the ditheophylline succinate suspention was attributed to the prevailing theophylline concentration in the mucosal solutions. The biopharmaceutical implication of these observations are discussed.", "contents": "Ditheophylline succinate: transfer of theophylline across everted rat intestinal sacs. The cumulative theophylline transfer rate across 10-cm everted rat intestinal sacs incubated at 37 degrees in pH 7.4 Krebs phosphate buffer was determined. A suspension of ditheophylline succinate ( a potential prodrug of theophylline) and a solution of theophylline at equimolar concentration were evaluated to determine the magnitude of the difference between the cumulative theophylline transfer rates from the two preparations. A linear concentration dependency for the rate across the intestinal wall was evidenced. The theophylline formation rate from ditheophylline succinate suspended in pH 7.4 Krebs buffer at 37 degrees followed apparent zero-order kinetics. The observed difference (fourfold) between the cumulative transfer rates estimated for the theophylline solution and the ditheophylline succinate suspention was attributed to the prevailing theophylline concentration in the mucosal solutions. The biopharmaceutical implication of these observations are discussed."}
{"id": "PMID:29957", "title": "Distribution of camazepam in rats and mice.", "content": "Camazepam, 5 mg/kg iv, was injected in rats and mice to study its distribution in the blood and brain. Peak blood levels were about 0.9 microgram/ml in rats and 0.6 microgram/ml in mice. Peak brain levels were about 1.5 microgram/g in rats and 0.8 microgram/g in mice. The apparent blood half-life of camazepam was 9 min in mice and 20 min in rats.", "contents": "Distribution of camazepam in rats and mice. Camazepam, 5 mg/kg iv, was injected in rats and mice to study its distribution in the blood and brain. Peak blood levels were about 0.9 microgram/ml in rats and 0.6 microgram/ml in mice. Peak brain levels were about 1.5 microgram/g in rats and 0.8 microgram/g in mice. The apparent blood half-life of camazepam was 9 min in mice and 20 min in rats."}
{"id": "PMID:29958", "title": "Inhibition of epinephrine oxidation in weak alkaline solutions.", "content": "The effect of sodium metabisulfite and cysteine on the oxidation of epinephrine in weak alkaline solutions was studied. The fluorescent intensity of the reacting mixture also was measured. Sodium metabisulfite in 2 x 10(-3) M NaOH at concentrations lower than 3 x 10(-5) M had no effect on epinephrine oxidation; however, in concentrations from 5 x 10(-5) to 3 x 10(-4) M, it greatly accelerated this process. Its inhibitory action appeared only in concentrations greater than 5 x 10(-4) M. The mechanism of these reactions also was explained. Cysteine in 2 x 10(-3) M NaOH inhibited the oxidation of epinephrine even in concentrations of 7 x 10(-5) M.", "contents": "Inhibition of epinephrine oxidation in weak alkaline solutions. The effect of sodium metabisulfite and cysteine on the oxidation of epinephrine in weak alkaline solutions was studied. The fluorescent intensity of the reacting mixture also was measured. Sodium metabisulfite in 2 x 10(-3) M NaOH at concentrations lower than 3 x 10(-5) M had no effect on epinephrine oxidation; however, in concentrations from 5 x 10(-5) to 3 x 10(-4) M, it greatly accelerated this process. Its inhibitory action appeared only in concentrations greater than 5 x 10(-4) M. The mechanism of these reactions also was explained. Cysteine in 2 x 10(-3) M NaOH inhibited the oxidation of epinephrine even in concentrations of 7 x 10(-5) M."}
{"id": "PMID:29960", "title": "The effect of neuroleptics on acetylcholine concentration and choline uptake in striatum: Implications for regulation of acetylcholine metabolism.", "content": "It has previously been shown that neuroleptic drugs block an apparently inhibitory influence of dopamine on cholinergic interneurons in striatum, thereby increasing acetylcholine turnover. In this study, systemic administration of the neuroleptic, fluphenazine, decreased the acetylcholine content in the striatum but not the neocortex of rats killed by focussed microwave irradiation. The effect was observed with doses of fluphenazine as low as 0.05 mg/kg, and was also seen after two other neuroleptics, spiroperidol (1 mg/kg) and haloperidol (4 mg/kg). In contrast, neither fluphenazine nor haloperidol pretreatment had any effect on the high affinity accumulation of choline by striatal synaptosomes. These observations suggest that after administration of dopamine receptor antagonists the release and metabolism of acetylcholine in the striatum is increased, but that a compensatory increase in choline uptake does not occur, thereby resulting in a temporary decrease in acetylcholine concentration. On the basis of these findings, we conclude that acetylcholine synthesis is regulated differently in the striatum than in other brain regions.", "contents": "The effect of neuroleptics on acetylcholine concentration and choline uptake in striatum: Implications for regulation of acetylcholine metabolism. It has previously been shown that neuroleptic drugs block an apparently inhibitory influence of dopamine on cholinergic interneurons in striatum, thereby increasing acetylcholine turnover. In this study, systemic administration of the neuroleptic, fluphenazine, decreased the acetylcholine content in the striatum but not the neocortex of rats killed by focussed microwave irradiation. The effect was observed with doses of fluphenazine as low as 0.05 mg/kg, and was also seen after two other neuroleptics, spiroperidol (1 mg/kg) and haloperidol (4 mg/kg). In contrast, neither fluphenazine nor haloperidol pretreatment had any effect on the high affinity accumulation of choline by striatal synaptosomes. These observations suggest that after administration of dopamine receptor antagonists the release and metabolism of acetylcholine in the striatum is increased, but that a compensatory increase in choline uptake does not occur, thereby resulting in a temporary decrease in acetylcholine concentration. On the basis of these findings, we conclude that acetylcholine synthesis is regulated differently in the striatum than in other brain regions."}
{"id": "PMID:29961", "title": "The effects of several narcotic analgesics on brain levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate in the rat.", "content": "The acute administration of levorphanol, morphine, anileridine, methadone, cyclazocine and pentazocine was found to increase brain levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MOPEG-SO4) in rats. Drug-induced increases in brain levels of this norepinephrine metabolite were dose-dependent and peak drug effects generally occurred 1 hr after intraperitoneal injection. Six to 8 hr after opiate agonist or partial agonist administration, MOEG-SO4 levels returned to control values or below. The narcotic effect appeared to be stereospecific, since high doses of d-methadone and dextrorphan produced either no change or only minimal increases in brain MOPEG-SO4 levels when compared with saline-treated controls. The relative potency of the analgesics tested in producing increases in brain MOPEG-SO4 levels appeared to correlate reasonably well with the ability of these drugs to produce other characteristic pharmacological effects. The drug-induced increases in brain MOPEG-SO4 levels were antagonized by naloxone. The rate of disappearance of MOPEG-SO4 from the brains of animals treated with pargyline was not decreased by the opiate agonists or partial agonists tested indicating that these drugs did not inhibit the acid transport process. These results indicate that the production of an increase in brain norepinephrine turnover is a specific component of the pharmacological actions of narcotic analgesics.", "contents": "The effects of several narcotic analgesics on brain levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate in the rat. The acute administration of levorphanol, morphine, anileridine, methadone, cyclazocine and pentazocine was found to increase brain levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MOPEG-SO4) in rats. Drug-induced increases in brain levels of this norepinephrine metabolite were dose-dependent and peak drug effects generally occurred 1 hr after intraperitoneal injection. Six to 8 hr after opiate agonist or partial agonist administration, MOEG-SO4 levels returned to control values or below. The narcotic effect appeared to be stereospecific, since high doses of d-methadone and dextrorphan produced either no change or only minimal increases in brain MOPEG-SO4 levels when compared with saline-treated controls. The relative potency of the analgesics tested in producing increases in brain MOPEG-SO4 levels appeared to correlate reasonably well with the ability of these drugs to produce other characteristic pharmacological effects. The drug-induced increases in brain MOPEG-SO4 levels were antagonized by naloxone. The rate of disappearance of MOPEG-SO4 from the brains of animals treated with pargyline was not decreased by the opiate agonists or partial agonists tested indicating that these drugs did not inhibit the acid transport process. These results indicate that the production of an increase in brain norepinephrine turnover is a specific component of the pharmacological actions of narcotic analgesics."}
{"id": "PMID:29962", "title": "In vivo desensitization to beta receptor mediated bronchodilator drugs in the rat: decreased beta receptor affinity.", "content": "When tracheas were isolated from rats pretreated with isoproterenol (ISO) or terbutaline, they were found to be considerably less sensitive to the relaxant action of ISO than tracheas which were isolated from saline-pretreated rats. The dissociation constant (Kb) for the propranolol-beta receptor complex was determined to be up to 400-fold larger in the tracheas isolated from beta agonist-pretreated rats (1.1 +/- 0.1 X 10(-6) M) than in tracheas isolated from saline-pretreated rats (3.0 +/- 0.3 X 10(-9) M). The longer the duration of pretreatment and the higher the dose of ISO or terbutaline used, the more attenuated was the response of tracheal smooth muscle to ISO, and the greater was the Kb for propranolol-beta receptor complex. These findings provide strong evidence which shows that desensitization, which occurs as a result of in vivo pretreatment with beta agonist drugs, results from pronounced reduction in this affinity of the beta receptors for beta agonist drugs. We observed that the in vivo treatment of rats with aminophylline (Amino), a phosphodiesterase inhibitor, did not affect the responsiveness of their isolated tracheas to either ISO or Amino. In addition, the responsiveness to Amino was determined in tracheal preparations taken from rats desensitized to ISO in vivo. The response to ISO was attenuated and the Kb for the propranolol-beta receptor complex was elevated (1.1 +/- 0.1 X 10(-6) M); however, Amino was half as effective in these tissues as in the saline control tissues. It is postulated, therefore, that the intracellular enzymes controlling the levels of cyclic adenosine monophosphate may be affected by the ISO-induced desensitization process, but are not affected by pretreatment with Amino.", "contents": "In vivo desensitization to beta receptor mediated bronchodilator drugs in the rat: decreased beta receptor affinity. When tracheas were isolated from rats pretreated with isoproterenol (ISO) or terbutaline, they were found to be considerably less sensitive to the relaxant action of ISO than tracheas which were isolated from saline-pretreated rats. The dissociation constant (Kb) for the propranolol-beta receptor complex was determined to be up to 400-fold larger in the tracheas isolated from beta agonist-pretreated rats (1.1 +/- 0.1 X 10(-6) M) than in tracheas isolated from saline-pretreated rats (3.0 +/- 0.3 X 10(-9) M). The longer the duration of pretreatment and the higher the dose of ISO or terbutaline used, the more attenuated was the response of tracheal smooth muscle to ISO, and the greater was the Kb for propranolol-beta receptor complex. These findings provide strong evidence which shows that desensitization, which occurs as a result of in vivo pretreatment with beta agonist drugs, results from pronounced reduction in this affinity of the beta receptors for beta agonist drugs. We observed that the in vivo treatment of rats with aminophylline (Amino), a phosphodiesterase inhibitor, did not affect the responsiveness of their isolated tracheas to either ISO or Amino. In addition, the responsiveness to Amino was determined in tracheal preparations taken from rats desensitized to ISO in vivo. The response to ISO was attenuated and the Kb for the propranolol-beta receptor complex was elevated (1.1 +/- 0.1 X 10(-6) M); however, Amino was half as effective in these tissues as in the saline control tissues. It is postulated, therefore, that the intracellular enzymes controlling the levels of cyclic adenosine monophosphate may be affected by the ISO-induced desensitization process, but are not affected by pretreatment with Amino."}
{"id": "PMID:29963", "title": "Post-tetanic enhancement of stimulus-induced muscarinic afterdischarge in the rat superior cervical ganglion.", "content": "The enhancement of asynchronous muscarinic ganglionic firing which follows a preganglionic nerve stimulus volley by high frequency repetitive conditioning stimuli was studied in the rat isolated superior cervical ganglion. Muscarinic afterdischarge which occurred in chlorisondamine-blocked ganglia was enhanced for up to 1 hr after a 40 Hz conditioning volley lasting 7.5 to 30 sec. Enhancement did not occur when release of acetylcholine was blocked by reducing the calcium in the modified Krebs' solution or when magnesium or manganese chlorides were added to the saline during the conditioning period. Metabolic inhibitors, dinitrophenol, sodium azide and ouabain, blocked the enhancement process but not the asynchronous muscarinic firing. Phenytoin, 10(-6) M, did not reduce the enhancement of firing. Dopamine, 5 X 10(-5) M, had no effect on muscarinic afterdischarge, but dibutyryl cyclic adenosine 3':5'-monophosphate, 5 and 10 X 10(=3) M, caused a 43 and 53% increase in the maximum amplitude of afterdischarge. Dibutyryl cyclic guanosine 3':5'-monophosphate had no effect on post-tetanic enhancement or afterdischarge in concentrations up to 1 X 10(-3) M. A working hypothesis is proposed: following a conditioning stimulus, a prolonged postsynaptic change occurs which results in an increased responsiveness to muscarinic agonists, and this change probably involves a metabolic reaction since it is reduced by metabolic inhibitors. Evidence to support the concept that dopamine is a modulator of enhancement in the rat superior cervical ganglion was not obtained.", "contents": "Post-tetanic enhancement of stimulus-induced muscarinic afterdischarge in the rat superior cervical ganglion. The enhancement of asynchronous muscarinic ganglionic firing which follows a preganglionic nerve stimulus volley by high frequency repetitive conditioning stimuli was studied in the rat isolated superior cervical ganglion. Muscarinic afterdischarge which occurred in chlorisondamine-blocked ganglia was enhanced for up to 1 hr after a 40 Hz conditioning volley lasting 7.5 to 30 sec. Enhancement did not occur when release of acetylcholine was blocked by reducing the calcium in the modified Krebs' solution or when magnesium or manganese chlorides were added to the saline during the conditioning period. Metabolic inhibitors, dinitrophenol, sodium azide and ouabain, blocked the enhancement process but not the asynchronous muscarinic firing. Phenytoin, 10(-6) M, did not reduce the enhancement of firing. Dopamine, 5 X 10(-5) M, had no effect on muscarinic afterdischarge, but dibutyryl cyclic adenosine 3':5'-monophosphate, 5 and 10 X 10(=3) M, caused a 43 and 53% increase in the maximum amplitude of afterdischarge. Dibutyryl cyclic guanosine 3':5'-monophosphate had no effect on post-tetanic enhancement or afterdischarge in concentrations up to 1 X 10(-3) M. A working hypothesis is proposed: following a conditioning stimulus, a prolonged postsynaptic change occurs which results in an increased responsiveness to muscarinic agonists, and this change probably involves a metabolic reaction since it is reduced by metabolic inhibitors. Evidence to support the concept that dopamine is a modulator of enhancement in the rat superior cervical ganglion was not obtained."}
{"id": "PMID:29965", "title": "Effect of luminal pH on acid secretion from Heidenhain pouches evoked by topical and parenteral stimulants.", "content": "1. An apparatus for intragastric titration has been devised and its validity tested. Both when attached to a beaker simulating a pouch and when attached to a pouch whose secretion was suppressed by infusing cimetidine, the apparatus accurately measured added acid when the endpoint setting was between pH 3.0 and 9.0. At pH 2.0 and 1.0 with liver extract and at pH 1.0 with saline, the amount of acid added was markedly underestimated.2. In dogs with vagally denervated pouches, during stimulation by I.V. infusion of histamine or pentagastrin, the rate of acid secretion as measured by intrapouch titration was uninfluenced by changes in luminal pH between 2.0 and 9.0. The apparent decrease in acid secretion at pH 1.0 could be shown to be due entirely to artifact in that no change in acid secretion was found when the gain in mass of acid was simultaneously measured by using a non-absorbable dilution indicator to measure volume gain and titration of samples to pH 7.0 to measure acid concentration.3. During stimulation of acid secretion by solutions of liver extract or of L-histidine instilled into the pouch, the rate of acid secretion was found to increase markedly as pH was increased from 3.0 to 9.0 thus confirming our earlier findings.4. We conclude that while stimulation of acid secretion by topical stimulants is highly dependent on luminal pH, secretion increasing as pH increases, stimulation by parenteral agents such as histamine and pentagastrin is not influenced by luminal pH in the range from pH 1.0 to 9.0.", "contents": "Effect of luminal pH on acid secretion from Heidenhain pouches evoked by topical and parenteral stimulants. 1. An apparatus for intragastric titration has been devised and its validity tested. Both when attached to a beaker simulating a pouch and when attached to a pouch whose secretion was suppressed by infusing cimetidine, the apparatus accurately measured added acid when the endpoint setting was between pH 3.0 and 9.0. At pH 2.0 and 1.0 with liver extract and at pH 1.0 with saline, the amount of acid added was markedly underestimated.2. In dogs with vagally denervated pouches, during stimulation by I.V. infusion of histamine or pentagastrin, the rate of acid secretion as measured by intrapouch titration was uninfluenced by changes in luminal pH between 2.0 and 9.0. The apparent decrease in acid secretion at pH 1.0 could be shown to be due entirely to artifact in that no change in acid secretion was found when the gain in mass of acid was simultaneously measured by using a non-absorbable dilution indicator to measure volume gain and titration of samples to pH 7.0 to measure acid concentration.3. During stimulation of acid secretion by solutions of liver extract or of L-histidine instilled into the pouch, the rate of acid secretion was found to increase markedly as pH was increased from 3.0 to 9.0 thus confirming our earlier findings.4. We conclude that while stimulation of acid secretion by topical stimulants is highly dependent on luminal pH, secretion increasing as pH increases, stimulation by parenteral agents such as histamine and pentagastrin is not influenced by luminal pH in the range from pH 1.0 to 9.0."}
{"id": "PMID:29966", "title": "Renal bicarbonate reabsorption in the new-born dog.", "content": "1. Renal bicarbonate reabsorption was measured in thirty new-born dogs 2-27 days of age. Plasma bicarbonate was varied in the puppies by exchanging their blood with blood containing high levels of bicarbonate and low levels of chloride.2. The exchange transfusion resulted in increases of plasma pH, P(CO2) and bicarbonate in the puppies without changing plasma sodium and potassium or glomerular filtration rate (g.f.r.) and body weight.3. There was no tubular reabsorption maximum (T(m)) for bicarbonate and reabsorption values as high as 50 muequiv/ml. g.f.r. could be attained. No animals excreted bicarbonate at plasma levels below 25 mM and some animals had plasma bicarbonate threshold values in excess of 40 mM.4. Bicarbonate reabsorption increased as arterial P(CO2) rose (r = 0.62) but this was due to the rise of filtered bicarbonate since (a) there was no correlation between arterial P(CO2) and bicarbonate reabsorption when factored by filtered bicarbonate and (b) lowering arterial P(CO2) by mechanical hyperventilation did not reduce bicarbonate reabsorption corrected for filtered load.5. Inhibition of renal carbonic anhydrase by acetazolamide (50 mg/kg) resulted in an inhibition of bicarbonate reabsorption of only 4.5 muequiv/ml. g.f.r. (less than 20% of the total). Even with renal carbonic anhydrase inhibited, there was no bicarbonate T(m) and bicarbonate reabsorption values as high as 40 muequiv/ml. g.f.r. could be attained.6. There was good correlation (r = 0.82) between inhibition of sodium and bicarbonate reabsorption during renal carbonic anhydrase inhibition. However, with carbonic anhydrase inhibited, there was no correlation between arterial P(CO2) and bicarbonate reabsorption.7. These results demonstrate that tubular bicarbonate reabsorption mechanisms in the new-born dog are as efficient as those reported for the adult as long as body fluid and plasma sodium and potassium levels are carefully maintained.8. The results are also consistent with a bicarbonate reabsorptive mechanism explained either by direct ionic bicarbonate reabsorption or by hydrogen ion secretion with diffusion of carbonic acid.", "contents": "Renal bicarbonate reabsorption in the new-born dog. 1. Renal bicarbonate reabsorption was measured in thirty new-born dogs 2-27 days of age. Plasma bicarbonate was varied in the puppies by exchanging their blood with blood containing high levels of bicarbonate and low levels of chloride.2. The exchange transfusion resulted in increases of plasma pH, P(CO2) and bicarbonate in the puppies without changing plasma sodium and potassium or glomerular filtration rate (g.f.r.) and body weight.3. There was no tubular reabsorption maximum (T(m)) for bicarbonate and reabsorption values as high as 50 muequiv/ml. g.f.r. could be attained. No animals excreted bicarbonate at plasma levels below 25 mM and some animals had plasma bicarbonate threshold values in excess of 40 mM.4. Bicarbonate reabsorption increased as arterial P(CO2) rose (r = 0.62) but this was due to the rise of filtered bicarbonate since (a) there was no correlation between arterial P(CO2) and bicarbonate reabsorption when factored by filtered bicarbonate and (b) lowering arterial P(CO2) by mechanical hyperventilation did not reduce bicarbonate reabsorption corrected for filtered load.5. Inhibition of renal carbonic anhydrase by acetazolamide (50 mg/kg) resulted in an inhibition of bicarbonate reabsorption of only 4.5 muequiv/ml. g.f.r. (less than 20% of the total). Even with renal carbonic anhydrase inhibited, there was no bicarbonate T(m) and bicarbonate reabsorption values as high as 40 muequiv/ml. g.f.r. could be attained.6. There was good correlation (r = 0.82) between inhibition of sodium and bicarbonate reabsorption during renal carbonic anhydrase inhibition. However, with carbonic anhydrase inhibited, there was no correlation between arterial P(CO2) and bicarbonate reabsorption.7. These results demonstrate that tubular bicarbonate reabsorption mechanisms in the new-born dog are as efficient as those reported for the adult as long as body fluid and plasma sodium and potassium levels are carefully maintained.8. The results are also consistent with a bicarbonate reabsorptive mechanism explained either by direct ionic bicarbonate reabsorption or by hydrogen ion secretion with diffusion of carbonic acid."}
{"id": "PMID:29969", "title": "Glutamine and glutamic acid uptake by rat renal brushborder membrane vesicles.", "content": "Glutamine uptake by rat renal brushborder vesicles occurred via two distinct saturable processes with Km values of 0.145 and 8.5 mM which were stimulated by both ionic and sodium gradients with a pH optimum of 6.8--7.1. Glutamic acid uptake also occurred by a two-component system with Km values of 0.016 and 3.60 mM. Both components were stimulated specifically by a sodium gradient. The low Km system for glutamic acid had a pH optimum of 7.2--7.4. Glutamine entry at 0.06 mM was inhibited by a variety of amino acids at 3 mM, including dibasic amino acids, glycine, valine, and phenylalanine. Glutamic acid entry at 0.06 mM was inhibited 20--30% by 3 mM phenylalanine, valine, alpha-aminoisobutyric acid, and glutamine. No metabolic alteration of glutamic acid was observed on incubation with membrane vesicles, but glutamine was significantly hydrolyzed to glutamic acid upon prolonged incubation. Hydrolysis of glutamine was negligible at 15 sec incubation which was employed for measurement of initial rate of entry. These studies provide support for the existence of an uptake system in the brushborder of the renal proximal tubule cell capable of handling the reabsorption of glutamine normally present in glomerular filtrate.", "contents": "Glutamine and glutamic acid uptake by rat renal brushborder membrane vesicles. Glutamine uptake by rat renal brushborder vesicles occurred via two distinct saturable processes with Km values of 0.145 and 8.5 mM which were stimulated by both ionic and sodium gradients with a pH optimum of 6.8--7.1. Glutamic acid uptake also occurred by a two-component system with Km values of 0.016 and 3.60 mM. Both components were stimulated specifically by a sodium gradient. The low Km system for glutamic acid had a pH optimum of 7.2--7.4. Glutamine entry at 0.06 mM was inhibited by a variety of amino acids at 3 mM, including dibasic amino acids, glycine, valine, and phenylalanine. Glutamic acid entry at 0.06 mM was inhibited 20--30% by 3 mM phenylalanine, valine, alpha-aminoisobutyric acid, and glutamine. No metabolic alteration of glutamic acid was observed on incubation with membrane vesicles, but glutamine was significantly hydrolyzed to glutamic acid upon prolonged incubation. Hydrolysis of glutamine was negligible at 15 sec incubation which was employed for measurement of initial rate of entry. These studies provide support for the existence of an uptake system in the brushborder of the renal proximal tubule cell capable of handling the reabsorption of glutamine normally present in glomerular filtrate."}
{"id": "PMID:29970", "title": "Cryptorchidism and testicular neoplasia.", "content": "A retrospective review of 20 cases of testicular neoplasia in cryptorchid patients is presented. These cases serve to emphasize the need for more effective diagnosis and management of the undescended testis. The various clinical presentations, diagnostic modalities, prognostic indicators, and types of management are reviewed. Due to its inaccessibility and array of clinical presentations, the intraabdominal testies tumor continues to be a diagnostic challenge. Strict attention to diagnostic cues and adherence to the management practices presented here would hopefully result in an overall decrease in testis tumors in the post-pubertal male.", "contents": "Cryptorchidism and testicular neoplasia. A retrospective review of 20 cases of testicular neoplasia in cryptorchid patients is presented. These cases serve to emphasize the need for more effective diagnosis and management of the undescended testis. The various clinical presentations, diagnostic modalities, prognostic indicators, and types of management are reviewed. Due to its inaccessibility and array of clinical presentations, the intraabdominal testies tumor continues to be a diagnostic challenge. Strict attention to diagnostic cues and adherence to the management practices presented here would hopefully result in an overall decrease in testis tumors in the post-pubertal male."}
{"id": "PMID:29971", "title": "Complement activation and hematologic, hemodynamic, and respiratory reactions early after soft-tissue injury.", "content": "The effect of soft-tissue trauma was studied in dogs. Following injuries to the hind leg an aggregation of thrombocytes in blood and trapping in the lung was noted. Injury was initially followed by leukopenia and later by leukocytosis. Early hemolysis of red cells was observed. The injury was accompanied by complement activation. Its possible relation to hemolysis, leukopenia, thrombocytopenia, and increased insufflation pressure is discussed.", "contents": "Complement activation and hematologic, hemodynamic, and respiratory reactions early after soft-tissue injury. The effect of soft-tissue trauma was studied in dogs. Following injuries to the hind leg an aggregation of thrombocytes in blood and trapping in the lung was noted. Injury was initially followed by leukopenia and later by leukocytosis. Early hemolysis of red cells was observed. The injury was accompanied by complement activation. Its possible relation to hemolysis, leukopenia, thrombocytopenia, and increased insufflation pressure is discussed."}
{"id": "PMID:29973", "title": "The congenitally dilated prostatic utricle.", "content": "A case of utricular dilatation in a child with recurrent urinary tract infection and associated genitourinary anomalies is presented. The embryology of the utricle and the relationship of the dilated utricle to the m\u00fcllerian duct regression factor are discussed. Clinical sequelae, diagnosis and management are outlined briefly.", "contents": "The congenitally dilated prostatic utricle. A case of utricular dilatation in a child with recurrent urinary tract infection and associated genitourinary anomalies is presented. The embryology of the utricle and the relationship of the dilated utricle to the m\u00fcllerian duct regression factor are discussed. Clinical sequelae, diagnosis and management are outlined briefly."}
{"id": "PMID:29976", "title": "Cardiovascular effects of isoproterenol and possible antagonistic actions of propranolol and perhexiline.", "content": "A beta-adrenergic blocking activity of perhexiline was compared with that of propanolol. In the Langendorff's preparation of rabbits, canine heart-lung preparations, open-chest dog preparations and hind-limbs of dogs, perhexiline failed to block isoproterenol-induced changes in cardiovascular functions, which were effectively blocked by propranolol. These data suggest that perhexiline is not a beta-adrenergic receptor blocking agent.", "contents": "Cardiovascular effects of isoproterenol and possible antagonistic actions of propranolol and perhexiline. A beta-adrenergic blocking activity of perhexiline was compared with that of propanolol. In the Langendorff's preparation of rabbits, canine heart-lung preparations, open-chest dog preparations and hind-limbs of dogs, perhexiline failed to block isoproterenol-induced changes in cardiovascular functions, which were effectively blocked by propranolol. These data suggest that perhexiline is not a beta-adrenergic receptor blocking agent."}
{"id": "PMID:29982", "title": "[Gamma-glutamyl transpeptidase activity in ischemic heart disease].", "content": "The blood plasma gamma-glutamyltranspeptidase (GGTP) activity was studied in 133 patients with macrofocal myocardial infarction, in 40 patients with microfocal myocardial infarction, in 30 patients with angina pectoris, and in 75 patients with cardiosclerosis and congestive cardiac failure. The activity of the enzyme increased in most patients with macrofocal myocardial infarction and in less than half of those with microfocal myocardial infarction beginning with the 3rd or 4th day, reached maximum by the 6th to 8th day of the disease, and then returned to normal levels in various lengths of time. In all patients with angina pectoris and acute left-ventricular failure the activity of the enzyme remained normal. It may be assumed from the results of the study that determination of GGTP activity in dynamics may be mainly employed in the diagnosis of macrofocal myocardial infarction, particularly after the first days of the disease. The enzyme test is hardly suitable for differential diagnosis between microfocal myocardial infarction and angina pectoris.", "contents": "[Gamma-glutamyl transpeptidase activity in ischemic heart disease]. The blood plasma gamma-glutamyltranspeptidase (GGTP) activity was studied in 133 patients with macrofocal myocardial infarction, in 40 patients with microfocal myocardial infarction, in 30 patients with angina pectoris, and in 75 patients with cardiosclerosis and congestive cardiac failure. The activity of the enzyme increased in most patients with macrofocal myocardial infarction and in less than half of those with microfocal myocardial infarction beginning with the 3rd or 4th day, reached maximum by the 6th to 8th day of the disease, and then returned to normal levels in various lengths of time. In all patients with angina pectoris and acute left-ventricular failure the activity of the enzyme remained normal. It may be assumed from the results of the study that determination of GGTP activity in dynamics may be mainly employed in the diagnosis of macrofocal myocardial infarction, particularly after the first days of the disease. The enzyme test is hardly suitable for differential diagnosis between microfocal myocardial infarction and angina pectoris."}
{"id": "PMID:29993", "title": "Physicians' assistants on a university cardiothoracic surgical service. A five-year update.", "content": "In 1973 two physicans' assistants (P.A.'s) were employed on a cardiothoracic surgical service at Emory University Hospital. In 1974 our initial experience with these paramedical personnel was presented to this Association. Since that time eight additional P.A.'s have been added to our service. They are now employed in four hospitals of the Emory University Woodruff Medical Center. New guidelines and regulations have been imposed at both the state and federal levels regarding P.A.'s, and their role in our center has become rather well defined. With over 1,700 cardiac cases and 600 thoracic cases per year to cover on our service, the P.A. has assumed a position of increasing importance both in operating room assistance and in preoperative and postoperative care. Since the university has maintained a constant number of residents and fellows during this interval, P.A.'s have filled needs of expanded clinical service in the various hospitals. In the pediatric and community hospitals associated with a university, the P.A. now functions as a junior house officer. In our university center, with a large resident staff, their role has become narrowed with definite guidelines. A Credentials Committee now governs the hiring of all P.A.'s by the University. When properly utilized and supervised, the P.A. can be a vital member of the cardiothoracic team. This report details our experience with P.A.'s for the past 5 years--culminating in a staff of ten P.A.'s working on our service in four types of hospitals within our university medical center.", "contents": "Physicians' assistants on a university cardiothoracic surgical service. A five-year update. In 1973 two physicans' assistants (P.A.'s) were employed on a cardiothoracic surgical service at Emory University Hospital. In 1974 our initial experience with these paramedical personnel was presented to this Association. Since that time eight additional P.A.'s have been added to our service. They are now employed in four hospitals of the Emory University Woodruff Medical Center. New guidelines and regulations have been imposed at both the state and federal levels regarding P.A.'s, and their role in our center has become rather well defined. With over 1,700 cardiac cases and 600 thoracic cases per year to cover on our service, the P.A. has assumed a position of increasing importance both in operating room assistance and in preoperative and postoperative care. Since the university has maintained a constant number of residents and fellows during this interval, P.A.'s have filled needs of expanded clinical service in the various hospitals. In the pediatric and community hospitals associated with a university, the P.A. now functions as a junior house officer. In our university center, with a large resident staff, their role has become narrowed with definite guidelines. A Credentials Committee now governs the hiring of all P.A.'s by the University. When properly utilized and supervised, the P.A. can be a vital member of the cardiothoracic team. This report details our experience with P.A.'s for the past 5 years--culminating in a staff of ten P.A.'s working on our service in four types of hospitals within our university medical center."}
{"id": "PMID:29994", "title": "Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators.", "content": "To examine the role of the oxygenator in the postperfusion lung syndrome, we studied 16 patients undergoing aorta-coronary bypass with a bubble oxygenator and 14 similar patients with a membrane oxygenator both before and for 2 days after the operation. To maintain the same pulmonary artery occluded pressure and hemoglobin level at the end of the surgical procedure, significantly more blood was required in the bubble than in the membrane group. Postoperative pulmonary dysfunction in the bubble group was characterized by increased pulmonary vascular resistance (PVR) and lung water. The increase in lung water was present after bubble oxygenation on three successive measurements, whereas there was no increase in lung water above control value at any measurement time in the membrane group. The bubble group had a significantly greater increase in PVR at the immediate postoperative study time than did the membrane group. PVR returned to control value for the duration of study. These differences in lung water and PVR measurements may be related to greater blood component trauma with a Travenol bubble oxygenator than with a membrane lung.", "contents": "Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators. To examine the role of the oxygenator in the postperfusion lung syndrome, we studied 16 patients undergoing aorta-coronary bypass with a bubble oxygenator and 14 similar patients with a membrane oxygenator both before and for 2 days after the operation. To maintain the same pulmonary artery occluded pressure and hemoglobin level at the end of the surgical procedure, significantly more blood was required in the bubble than in the membrane group. Postoperative pulmonary dysfunction in the bubble group was characterized by increased pulmonary vascular resistance (PVR) and lung water. The increase in lung water was present after bubble oxygenation on three successive measurements, whereas there was no increase in lung water above control value at any measurement time in the membrane group. The bubble group had a significantly greater increase in PVR at the immediate postoperative study time than did the membrane group. PVR returned to control value for the duration of study. These differences in lung water and PVR measurements may be related to greater blood component trauma with a Travenol bubble oxygenator than with a membrane lung."}
{"id": "PMID:29995", "title": "Protection of the ischemic myocardium. Volume-duration relationships and the efficacy of myocardial infusates.", "content": "In studies in the isolated rat heart that were designed to optimize the composition of the infusion conditions for a cardioplegic protective solutuin, we have observed a complex relationship between the duration and volume of infusion and the extent of tissue protection. Our results would indicate that solutions, such as that formulated at St. Thomas' Hospital, which are based on extracellular electrolyte content, afford (after a brief equilibration period) a constant degree of protection, irrespective of infusion volume or duration. In contrast other solutions, such as the Bretschneider solution, which have extremes of electrolyre concentration, are associated with a complex dose-response relationship. In the latter instance, infusion of small volumes for short durations affords an increasing degree of protection against ischemia. Increasing the infusate volume may result in a progressive loss of protection. Excessive infusion may lead to an exacerbation of ischemia-induced damage. Our studies suggest that the relative patterns and rates of re-equilibration of various ions, especially sodium and calcium, during infusion may play a major role in determining the efficacy of the infusate.", "contents": "Protection of the ischemic myocardium. Volume-duration relationships and the efficacy of myocardial infusates. In studies in the isolated rat heart that were designed to optimize the composition of the infusion conditions for a cardioplegic protective solutuin, we have observed a complex relationship between the duration and volume of infusion and the extent of tissue protection. Our results would indicate that solutions, such as that formulated at St. Thomas' Hospital, which are based on extracellular electrolyte content, afford (after a brief equilibration period) a constant degree of protection, irrespective of infusion volume or duration. In contrast other solutions, such as the Bretschneider solution, which have extremes of electrolyre concentration, are associated with a complex dose-response relationship. In the latter instance, infusion of small volumes for short durations affords an increasing degree of protection against ischemia. Increasing the infusate volume may result in a progressive loss of protection. Excessive infusion may lead to an exacerbation of ischemia-induced damage. Our studies suggest that the relative patterns and rates of re-equilibration of various ions, especially sodium and calcium, during infusion may play a major role in determining the efficacy of the infusate."}
{"id": "PMID:29997", "title": "New health professional practice patterns.", "content": "Career patterns and practice correlates of 143 New Health Professionals (NHPs) educated at one institution are studied to determine similarities among different types of practitioners (Health Associates and Nurse Practitioners). Employment since graduation has been high with low job turnover. Nurse Practitioners (NPs) are found most often in metropolitan areas, while over 50 per cent of Health Associates (HAs) are employed in rural settings. More NPs work in hospitals than HAs, who have a higher rate of employment in private practices, HAs are also involved in a wider range of medical specialties than NPs. In terms of patient care, HAs see more patients than NPs and also have larger primary care caseloads. From a functional perspective, only minimal differences are found in comparing the activities of the practitioners. Most NHPs have high job satisfaction, although HAs anticipate a high rate of job turnover; no differences were found in levels of perceived responsibility nor in the amount of supervision in patient care. Although there were only small differences in the activities of the two groups, numerous contextual and practice correlates were found to differentiate the NHPs, a finding which argues against the current practice of conceptualizing NHPs as a single group.", "contents": "New health professional practice patterns. Career patterns and practice correlates of 143 New Health Professionals (NHPs) educated at one institution are studied to determine similarities among different types of practitioners (Health Associates and Nurse Practitioners). Employment since graduation has been high with low job turnover. Nurse Practitioners (NPs) are found most often in metropolitan areas, while over 50 per cent of Health Associates (HAs) are employed in rural settings. More NPs work in hospitals than HAs, who have a higher rate of employment in private practices, HAs are also involved in a wider range of medical specialties than NPs. In terms of patient care, HAs see more patients than NPs and also have larger primary care caseloads. From a functional perspective, only minimal differences are found in comparing the activities of the practitioners. Most NHPs have high job satisfaction, although HAs anticipate a high rate of job turnover; no differences were found in levels of perceived responsibility nor in the amount of supervision in patient care. Although there were only small differences in the activities of the two groups, numerous contextual and practice correlates were found to differentiate the NHPs, a finding which argues against the current practice of conceptualizing NHPs as a single group."}
{"id": "PMID:30009", "title": "[Biochemical and pathophysiological aspects of alcohol metabolism (author's transl)].", "content": "The metabolism of ethanol to acetaldehyde proceeds in the liver via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS), whereas catalase plays no significant role. ADH is localized in the cytosol, required required NAD+ as cofactor and exhibits a pH optimum in the alkaline range and a Km of less than 2 mM for ethanol. Conversely, the MEOS resides in the endoplasmic reticulum, requires NADPH and O2, is inhibited by CO, and exhibits a Km of about 10 mM for ethanol. The microsomal system also metabolizes higher aliphatic alcohols such as butanol which is not a substrate for catalase. Moreover, it could be separated from ADH and catalase by column chromatography. The MEOS exhibits a variety of properties similar to those of other microsomal drug metabolizing enzymes and is characterized by inducibility of its activity following chronic alcohol consumption, which suggests the involvement of the microsomal system in the adaptive enhancement of ethanol clearance commonly observed in alcoholics.", "contents": "[Biochemical and pathophysiological aspects of alcohol metabolism (author's transl)]. The metabolism of ethanol to acetaldehyde proceeds in the liver via alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system (MEOS), whereas catalase plays no significant role. ADH is localized in the cytosol, required required NAD+ as cofactor and exhibits a pH optimum in the alkaline range and a Km of less than 2 mM for ethanol. Conversely, the MEOS resides in the endoplasmic reticulum, requires NADPH and O2, is inhibited by CO, and exhibits a Km of about 10 mM for ethanol. The microsomal system also metabolizes higher aliphatic alcohols such as butanol which is not a substrate for catalase. Moreover, it could be separated from ADH and catalase by column chromatography. The MEOS exhibits a variety of properties similar to those of other microsomal drug metabolizing enzymes and is characterized by inducibility of its activity following chronic alcohol consumption, which suggests the involvement of the microsomal system in the adaptive enhancement of ethanol clearance commonly observed in alcoholics."}
{"id": "PMID:30019", "title": "The regulations of renal ammoniagenesis in the rat by extracellular factors. I. The combined effects of acidosis and physiologic fuels.", "content": "Substrate oxidation by rat kidney slices regulates renal ammoniagenesis from glutamine. At concentrations close to those expected in plasma, lactate alone, or combined with other renal fuels, inhibits ammoniagenesis markedly; glucose and citrate decrease ammoniagenesis slightly. However, lactate, citrate, and glucose inhibit ammoniagenesis of kidney slices from acidotic rats less than ammoniagenesis of kidney slices from control rats. Lesser inhibition of ammoniagenesis is seen also when acidotic slices rather than control slices are incubated in the presence of all the tested substrates combined in the same medium. In addition to decreasing the ammoniagenesis of renal slices from control rats, the presence of lactate causes an augmented accumulation of glutamate. In contrast, adding lactate to acidotic slices does not increase glutamate accumulation nearly as much. When glutamate is substituted for glutamine in the medium, lactate still decreases ammonia production, but to a lesser extent with acidotic slices. Changes in medium pH from 7.0 to 7.8 have no, or only small, overall effects on net renal slice ammonia production from glutamine under any of the circumstances tested. We conclude that lactate alone and combined with other substrates decreases ammoniagenesis primarily at the glutamate dehydrogenase step and that slices from acidotic rats are relatively resistant to substrate mediated inhibition.", "contents": "The regulations of renal ammoniagenesis in the rat by extracellular factors. I. The combined effects of acidosis and physiologic fuels. Substrate oxidation by rat kidney slices regulates renal ammoniagenesis from glutamine. At concentrations close to those expected in plasma, lactate alone, or combined with other renal fuels, inhibits ammoniagenesis markedly; glucose and citrate decrease ammoniagenesis slightly. However, lactate, citrate, and glucose inhibit ammoniagenesis of kidney slices from acidotic rats less than ammoniagenesis of kidney slices from control rats. Lesser inhibition of ammoniagenesis is seen also when acidotic slices rather than control slices are incubated in the presence of all the tested substrates combined in the same medium. In addition to decreasing the ammoniagenesis of renal slices from control rats, the presence of lactate causes an augmented accumulation of glutamate. In contrast, adding lactate to acidotic slices does not increase glutamate accumulation nearly as much. When glutamate is substituted for glutamine in the medium, lactate still decreases ammonia production, but to a lesser extent with acidotic slices. Changes in medium pH from 7.0 to 7.8 have no, or only small, overall effects on net renal slice ammonia production from glutamine under any of the circumstances tested. We conclude that lactate alone and combined with other substrates decreases ammoniagenesis primarily at the glutamate dehydrogenase step and that slices from acidotic rats are relatively resistant to substrate mediated inhibition."}
{"id": "PMID:30020", "title": "Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat.", "content": "To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different.", "contents": "Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat. To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different."}
{"id": "PMID:30022", "title": "[Mechanism of the oxidation of divalent iron and manganese by iron bacteria developing in a neutral acidic medium].", "content": "The paper confirms the existence of a peroxide mechanism involved in oxidation of iron and manganeses by the most typical iron bacteria growing at neutral acidity of the medium. Oxidation of bivalent iron and manganese is accomplished by the simultaneous action of catalase and hydrogen peroxide produced in the respiratory chain in the course of oxidation of organic substances. Catalase performs the peroxidase function in these processes. The possibility of these biological reactions to occur and the necessary conditions have been studied in vitro. Possible variants of iron and manganese oxidation by iron bacteria are discussed, including the conditions for \"symbiotic\" oxidation of manganese by mixed cultures of microorganisms.", "contents": "[Mechanism of the oxidation of divalent iron and manganese by iron bacteria developing in a neutral acidic medium]. The paper confirms the existence of a peroxide mechanism involved in oxidation of iron and manganeses by the most typical iron bacteria growing at neutral acidity of the medium. Oxidation of bivalent iron and manganese is accomplished by the simultaneous action of catalase and hydrogen peroxide produced in the respiratory chain in the course of oxidation of organic substances. Catalase performs the peroxidase function in these processes. The possibility of these biological reactions to occur and the necessary conditions have been studied in vitro. Possible variants of iron and manganese oxidation by iron bacteria are discussed, including the conditions for \"symbiotic\" oxidation of manganese by mixed cultures of microorganisms."}
{"id": "PMID:30023", "title": "[Effect of the redox potential on the growth of aerobic microorganisms].", "content": "The effect of redox potential was studied on the growth of the following aerobic microorganisms: Candida utilis, Bacillus megaterium, Pseudomonas fluorescens. The action of oxidizing agents (K3Fe(CN)6, KIO3, K2Cr207 and KMnO4) and reducing agents (ascorbic acid, sodium thioglycolate, K4Fe (CN)6 and Na2S2O3) on the growth rate was investigated. K3Fe(CN)6, ascorbic acid, sodium thioglycolate and K4Fe(CN)6 were found to be suitable for buffering the Eh of the medium. The potential could be shifted by 50--200 mV by adding various reducing and oxidizing agents. The rate of growth of C. utilis, Bac. megaterium and Ps. fluorescens did not depend on the potential value.", "contents": "[Effect of the redox potential on the growth of aerobic microorganisms]. The effect of redox potential was studied on the growth of the following aerobic microorganisms: Candida utilis, Bacillus megaterium, Pseudomonas fluorescens. The action of oxidizing agents (K3Fe(CN)6, KIO3, K2Cr207 and KMnO4) and reducing agents (ascorbic acid, sodium thioglycolate, K4Fe (CN)6 and Na2S2O3) on the growth rate was investigated. K3Fe(CN)6, ascorbic acid, sodium thioglycolate and K4Fe(CN)6 were found to be suitable for buffering the Eh of the medium. The potential could be shifted by 50--200 mV by adding various reducing and oxidizing agents. The rate of growth of C. utilis, Bac. megaterium and Ps. fluorescens did not depend on the potential value."}
{"id": "PMID:30025", "title": "[Alcohol dehydrogenase activity of the subcellular fractions of Torulopsis candida yeasts grown on glucose and hexadecane].", "content": "The activity of alcohol dehydrogenase was compared in subcellular fractions of Torulopsis candida grown on glucose (\"glucose cells\") and on hexadecane (\"hexadecane cells\"). Two groups of alcohol dehydrogenases (ADH) were found to be present in the cells: (1) soluble ADH located in the cytosol and (2) ADH bound to the membrane structures and located in the mitochondria and other cell structures. Soluble ADH of \"glucose cells\" actively dehydrated all alcohols tested from C2 to C16. Ln \"hexadecane cells\", the activity was low or absent. ADH bound to the cell structures dehydrated mainly C5--C16 alcohols; the activity of these ADH was almost by an order of magnitude higher in the \"hexadecane cells\" as compared to the \"glucose cells\" (in contrast to soluble ADH). The character of changes in the activity of ADH toward various alcohols in the course of physiological adaptation of the yeast to oxidation of glucose and hexadecane suggests that both soluble and bound ADH contain at least two ADH, one of which is specific to lower alcohols and the other to higher alcohols.", "contents": "[Alcohol dehydrogenase activity of the subcellular fractions of Torulopsis candida yeasts grown on glucose and hexadecane]. The activity of alcohol dehydrogenase was compared in subcellular fractions of Torulopsis candida grown on glucose (\"glucose cells\") and on hexadecane (\"hexadecane cells\"). Two groups of alcohol dehydrogenases (ADH) were found to be present in the cells: (1) soluble ADH located in the cytosol and (2) ADH bound to the membrane structures and located in the mitochondria and other cell structures. Soluble ADH of \"glucose cells\" actively dehydrated all alcohols tested from C2 to C16. Ln \"hexadecane cells\", the activity was low or absent. ADH bound to the cell structures dehydrated mainly C5--C16 alcohols; the activity of these ADH was almost by an order of magnitude higher in the \"hexadecane cells\" as compared to the \"glucose cells\" (in contrast to soluble ADH). The character of changes in the activity of ADH toward various alcohols in the course of physiological adaptation of the yeast to oxidation of glucose and hexadecane suggests that both soluble and bound ADH contain at least two ADH, one of which is specific to lower alcohols and the other to higher alcohols."}
{"id": "PMID:30034", "title": "[A field study with the combination of Pindolol and Clopamid in antihpertensive therapy (author's transl)].", "content": "In a field study comprising 678 patients with arterial hypertension efficacy and tolerance of the stable combination VKB 105 consisting of 10 mg Pindolol (Visken) and 5 mg Clopamid (Brinaldix) were investigated. Treatment with 1--2 tablets of VKB per day resulted in a successful therapy in 94% of all patients corresponding on the average to a reduction in blood pressure to 145/85 mm Hg within 14 days. In mean arterial pressures ranging between 120 and 170 mm Hg a positive linear relationship between the individual initial value and the hypotensive effect of the combination could be observed. A controlled omission trial disclosed qualitatively the respective contribution to the effect of the two components Pindolol and Clopamid. With a systematic case control of the serum potassium under the combined therapy with VKB 105 and during a monotherapy with Clopamid and antihypokalaemic effect of Pindolol could be demonstrated diminishing the tendency for potassium loss. The result revealed a far-reaching potassium neutrality of diuresis-depending stimulation of renin by the beta-receptor blocker. In 61 patients altogether subjective side-effects could be recorded, such as vertigo (5%), palpitations (2.8%), fatigue (2%), insomina (1.9%), nausea (1.7%) and vomiting (0.8%). Laboratory controls gave no indication for clinically relevant changes.", "contents": "[A field study with the combination of Pindolol and Clopamid in antihpertensive therapy (author's transl)]. In a field study comprising 678 patients with arterial hypertension efficacy and tolerance of the stable combination VKB 105 consisting of 10 mg Pindolol (Visken) and 5 mg Clopamid (Brinaldix) were investigated. Treatment with 1--2 tablets of VKB per day resulted in a successful therapy in 94% of all patients corresponding on the average to a reduction in blood pressure to 145/85 mm Hg within 14 days. In mean arterial pressures ranging between 120 and 170 mm Hg a positive linear relationship between the individual initial value and the hypotensive effect of the combination could be observed. A controlled omission trial disclosed qualitatively the respective contribution to the effect of the two components Pindolol and Clopamid. With a systematic case control of the serum potassium under the combined therapy with VKB 105 and during a monotherapy with Clopamid and antihypokalaemic effect of Pindolol could be demonstrated diminishing the tendency for potassium loss. The result revealed a far-reaching potassium neutrality of diuresis-depending stimulation of renin by the beta-receptor blocker. In 61 patients altogether subjective side-effects could be recorded, such as vertigo (5%), palpitations (2.8%), fatigue (2%), insomina (1.9%), nausea (1.7%) and vomiting (0.8%). Laboratory controls gave no indication for clinically relevant changes."}
{"id": "PMID:30039", "title": "Mapping of the locus involved in the catabolic oxidation of D-amino acids in Pseudomonas aeruginosa PAO.", "content": "Mutants of Pseudomonas aeruginosa PAO deficient in their utilization of DL-valine have been found to have lost their capacity to utilize DL-alanine and L-proline. Use of conjugal and transductional mediated gene transfers have established the chromosomal location of this gene and also its pleotropic function in the induction of the D-amino acid oxidase, involved in the oxidative utilization of DL-valine, DL-alanine and L-proline. These point mutations are clustered in a single locus designated as Val D and mapped around the 19th minute on the chromosome.", "contents": "Mapping of the locus involved in the catabolic oxidation of D-amino acids in Pseudomonas aeruginosa PAO. Mutants of Pseudomonas aeruginosa PAO deficient in their utilization of DL-valine have been found to have lost their capacity to utilize DL-alanine and L-proline. Use of conjugal and transductional mediated gene transfers have established the chromosomal location of this gene and also its pleotropic function in the induction of the D-amino acid oxidase, involved in the oxidative utilization of DL-valine, DL-alanine and L-proline. These point mutations are clustered in a single locus designated as Val D and mapped around the 19th minute on the chromosome."}
{"id": "PMID:30042", "title": "[Fenfluramin (ponderax) intoxications in children (author's transl)].", "content": "4 cases of accidental fenfluramine poisoning in children are reported. Excitation, coma, convulsions, tachycardia, mydriasis, nystagmus, and rubeosis of the face were the most important signs. They appeared 30--60 min after ingestion, and some of them lasted for several days. 2 children had severe trismus and therefore had to be given muscle relaxants before intubation and gastric lavage became possible. These observations agree well with  informations collected in our poisoning control center and with previously published data. Less than 5 mg/kg of body weight are toxic, 5--10 mg/kg may produce coma and convulsions, and the smallest lethal doses were 28,7 and 33,3 mg/kg. Early gastric lavage, good monitoring of the vital functions and, if necessary, administration of anticonvulsive drugs, beta-blocking agents, lidocaine, chlorpromazine, and artificial ventilation and cardiac defibrillation are the most important therapeutical measures.", "contents": "[Fenfluramin (ponderax) intoxications in children (author's transl)]. 4 cases of accidental fenfluramine poisoning in children are reported. Excitation, coma, convulsions, tachycardia, mydriasis, nystagmus, and rubeosis of the face were the most important signs. They appeared 30--60 min after ingestion, and some of them lasted for several days. 2 children had severe trismus and therefore had to be given muscle relaxants before intubation and gastric lavage became possible. These observations agree well with  informations collected in our poisoning control center and with previously published data. Less than 5 mg/kg of body weight are toxic, 5--10 mg/kg may produce coma and convulsions, and the smallest lethal doses were 28,7 and 33,3 mg/kg. Early gastric lavage, good monitoring of the vital functions and, if necessary, administration of anticonvulsive drugs, beta-blocking agents, lidocaine, chlorpromazine, and artificial ventilation and cardiac defibrillation are the most important therapeutical measures."}
{"id": "PMID:30043", "title": "[Therapy with beta-blocking-agents (author's transl)].", "content": "Within the last 10 years the indications for a therapeutic regimen with beta-blocking-agents have been differentiated: coronary heart disease with angina pectoris (interval regimen), essential hypertension, especially in younger persons; hyperkinetic heart syndrome; thyreotoxikosis, symptomatic therapy; heart rhythm disorders, extrasystolic or tachysystolic; neurologic-psychiatric diseases. The development of the newer beta-blocking-agents has effected different kinetic data (f.i. long acting effects of Tenormin) and a increased cardioselectivity. The recommendations for the therapeutic regimen have to be outlined to the underlying diseases. The sensitivity against the drugs depends on remarkable individual differences, with the consequence of a careful and low dosage in the beginning in each case. The side-effects of beta-blocking-agents are presumably: bradycardia, bronchospasm, fatigue, adynamia, myocardial insufficiency, gastrointestinal symptoms, hypoglycemia, hypotension.", "contents": "[Therapy with beta-blocking-agents (author's transl)]. Within the last 10 years the indications for a therapeutic regimen with beta-blocking-agents have been differentiated: coronary heart disease with angina pectoris (interval regimen), essential hypertension, especially in younger persons; hyperkinetic heart syndrome; thyreotoxikosis, symptomatic therapy; heart rhythm disorders, extrasystolic or tachysystolic; neurologic-psychiatric diseases. The development of the newer beta-blocking-agents has effected different kinetic data (f.i. long acting effects of Tenormin) and a increased cardioselectivity. The recommendations for the therapeutic regimen have to be outlined to the underlying diseases. The sensitivity against the drugs depends on remarkable individual differences, with the consequence of a careful and low dosage in the beginning in each case. The side-effects of beta-blocking-agents are presumably: bradycardia, bronchospasm, fatigue, adynamia, myocardial insufficiency, gastrointestinal symptoms, hypoglycemia, hypotension."}
{"id": "PMID:30044", "title": "Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants.", "content": "Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus.", "contents": "Lymphocytic bronchitis associated with graft-versus-host disease in recipients of bone-marrow transplants. Graft-versus-host disease, a complication of allogeneic bone-marrow transplantation, involves primarily the skin, liver and intestines, but may also be associated with pneumonia. To determine the relation of graft-versus-host disease with pneumonia, we evaluated the autopsies of 59 allogeneic and two autologous recipients and 74 control patients with various pulmonary diseases, who had not received a bone-marrow transplant. Lymphocytic bronchitis, characterized by lymphocyte-associated necrosis of the bronchial mucosa and often the submucosal glands, was present in 12 of 20 patients with Grade 2 or greater graft-versus-host disease but in only three of 39 with Grade 0 to 1 disease (P less than 0.0005). Onset of respiratory disease correlated with the time of onset of graft-versus-host disease. Patients with lymphocytic bronchitis had a higher incidence of bronchopneumonia and acute bronchitis of the lower respiratory tract. Lymphocytic bronchitis did not occur in the controls and appears to be a component of graft-versus-host disease that leads to bronchopneumonia, probably through destruction of the mucociliary apparatus."}
{"id": "PMID:30046", "title": "Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium.", "content": "Progesterone reinitiates meiotic maturation in Xenopus oocytes. Evidence is reported which indicates that the steroid acts at the level of the cell surface and suggests that an induced change of Ca2+ distribution triggers in turn a cascade of cytoplasmic events including protein synthesis and germinal vesicle (nucleus) breakdown. These novel features of steroid hormone action in amphibian oocytes are discussed in relation to presently accepted views of the mechanism of action of steroid hormones in somatic cells.", "contents": "Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium. Progesterone reinitiates meiotic maturation in Xenopus oocytes. Evidence is reported which indicates that the steroid acts at the level of the cell surface and suggests that an induced change of Ca2+ distribution triggers in turn a cascade of cytoplasmic events including protein synthesis and germinal vesicle (nucleus) breakdown. These novel features of steroid hormone action in amphibian oocytes are discussed in relation to presently accepted views of the mechanism of action of steroid hormones in somatic cells."}
{"id": "PMID:30047", "title": "Benzodiazepines and central inhibitory mechanisms.", "content": "The effect of diazepam was evaluated on spontaneous activity and drug- and electrically-elicited inhibitions of neuronal activity. Doses of diazepam which did not change spontaneous firing rates markedly enhanced GABA-mediated inhibitions in rat cerebellum in situ and in tissue cultures of rat hypothalamus. The effects of diazepam were readily reversible, and could be antagonized by picrotoxin; no effect on glycine or norepinephrine-induced inhibition was seen. It is concluded that actions of diazepam are mediated, at least in part, by a specific increase in GABA-mediated inhibition in the central nervous system.", "contents": "Benzodiazepines and central inhibitory mechanisms. The effect of diazepam was evaluated on spontaneous activity and drug- and electrically-elicited inhibitions of neuronal activity. Doses of diazepam which did not change spontaneous firing rates markedly enhanced GABA-mediated inhibitions in rat cerebellum in situ and in tissue cultures of rat hypothalamus. The effects of diazepam were readily reversible, and could be antagonized by picrotoxin; no effect on glycine or norepinephrine-induced inhibition was seen. It is concluded that actions of diazepam are mediated, at least in part, by a specific increase in GABA-mediated inhibition in the central nervous system."}
{"id": "PMID:30069", "title": "Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood.", "content": "The Bohr factor, phi = delta log Po2/deltapH, was determined at various levels of hemoglobin O2 saturation (SO2) in fresh whole blood of the duck. Plasma pH was varied by either changing PCO2 of the blood at constant base excess (CO2 Bohr factor, phiCO2) or by addition of NaHCO3 and HCl at constant PCO2 (fixed acid BOHR factor, phiAH). No differences were found between phiCO2 and phiAH at SO2 levels between 20 and 85%, and there was no saturation dependence of the Bohr factor, its average value being -0.44. It is concluded that in whole blood of this bird species CO2 exerts no direct effect on the O2 affinity of hemoglobin.", "contents": "Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood. The Bohr factor, phi = delta log Po2/deltapH, was determined at various levels of hemoglobin O2 saturation (SO2) in fresh whole blood of the duck. Plasma pH was varied by either changing PCO2 of the blood at constant base excess (CO2 Bohr factor, phiCO2) or by addition of NaHCO3 and HCl at constant PCO2 (fixed acid BOHR factor, phiAH). No differences were found between phiCO2 and phiAH at SO2 levels between 20 and 85%, and there was no saturation dependence of the Bohr factor, its average value being -0.44. It is concluded that in whole blood of this bird species CO2 exerts no direct effect on the O2 affinity of hemoglobin."}
{"id": "PMID:30070", "title": "Carbon dioxide and acid base balance in the isolated rat diaphragm.", "content": "A method for measuring the net acid base exchange in an isolated rat diaphragm preparation is described. Particular attention is paid to monitoring the functional status and maintaining optimal diffusion conditions. A steady net acid efflux of the order of 250 n mole/g-min is found in the resting state. This increases following a series of isometric contractions. In the resting state the total measured lactate + pyruvate efflux was found to be less than the net acid efflux. The net acid efflux increases following a sudden decrease in pCO2 and decreases or reverses following a sudden increase in pCO2 or a decrease in external bicarbonate. The net base loss during a period of 1 h following the exposure to high (20%) CO2 represents a large fraction of the predicted total bicarbonate generated within the fibres by non-bicarbonate buffers. This indicates that the effects of intracellular non-bicarbonate buffers can be transmitted to the external solution following a change in pCO2. The most plausible explanation is that passive bicarbonate ion movements are responsible. Values of the 'apparent PHCO3' have been calculated and vary under different conditions from a value of 1.3 X 10(-7) to 1.9 X 10(-6) cm-s-1.", "contents": "Carbon dioxide and acid base balance in the isolated rat diaphragm. A method for measuring the net acid base exchange in an isolated rat diaphragm preparation is described. Particular attention is paid to monitoring the functional status and maintaining optimal diffusion conditions. A steady net acid efflux of the order of 250 n mole/g-min is found in the resting state. This increases following a series of isometric contractions. In the resting state the total measured lactate + pyruvate efflux was found to be less than the net acid efflux. The net acid efflux increases following a sudden decrease in pCO2 and decreases or reverses following a sudden increase in pCO2 or a decrease in external bicarbonate. The net base loss during a period of 1 h following the exposure to high (20%) CO2 represents a large fraction of the predicted total bicarbonate generated within the fibres by non-bicarbonate buffers. This indicates that the effects of intracellular non-bicarbonate buffers can be transmitted to the external solution following a change in pCO2. The most plausible explanation is that passive bicarbonate ion movements are responsible. Values of the 'apparent PHCO3' have been calculated and vary under different conditions from a value of 1.3 X 10(-7) to 1.9 X 10(-6) cm-s-1."}
{"id": "PMID:30083", "title": "Modification of DNA by aflatoxin B1 creates alkali-labile lesions in DNA at positions of guanine and adenine.", "content": "The damage to DNA by the hepatocarcinogen aflatoxin B1 was investigated. A DNA fragment of known sequence of the lactose promoter-operator region was used as a substrate for modification by aflatoxin B1. The DNA was incubated with aflatoxin B1 in crude mammalian liver extracts or with purified microsomes. Treatment of the DNA incubated in the complete system with either 1 M piperidine or 0.1 M NaOH at 90 degrees revealed alkali-labile lesions in the DNA. The exact location of the cleavage site was determined by comparison of the length of the cleavage products with the known sequence on polyacrylamide gels. The lengths of the cleavage products were the same as those produced by alkali-induced breakage of the same sequence of DNA that had been modified with dimethyl sulfate. The major cleavage products of the aflatoxin B1-modified DNA were at positions of guanine and the minor cleavage products were at positions of adenine. These studies show that modification of DNA by aflatoxin B1 creates alkali-labile sites at positions of guanine and, to a lesser extent, adenine.", "contents": "Modification of DNA by aflatoxin B1 creates alkali-labile lesions in DNA at positions of guanine and adenine. The damage to DNA by the hepatocarcinogen aflatoxin B1 was investigated. A DNA fragment of known sequence of the lactose promoter-operator region was used as a substrate for modification by aflatoxin B1. The DNA was incubated with aflatoxin B1 in crude mammalian liver extracts or with purified microsomes. Treatment of the DNA incubated in the complete system with either 1 M piperidine or 0.1 M NaOH at 90 degrees revealed alkali-labile lesions in the DNA. The exact location of the cleavage site was determined by comparison of the length of the cleavage products with the known sequence on polyacrylamide gels. The lengths of the cleavage products were the same as those produced by alkali-induced breakage of the same sequence of DNA that had been modified with dimethyl sulfate. The major cleavage products of the aflatoxin B1-modified DNA were at positions of guanine and the minor cleavage products were at positions of adenine. These studies show that modification of DNA by aflatoxin B1 creates alkali-labile sites at positions of guanine and, to a lesser extent, adenine."}
{"id": "PMID:30084", "title": "Functional lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli: temperature and pH dependence of dansyl-galactoside binding.", "content": "6'-(N-Dansyl)aminohexyl-1-thio-beta-D-galactopyranoside binds specifically to the lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli. Binding can be induced by substrate oxidation (generation of an electrochemical gradient of protons), by potassium efflux in the presence of valinomycin (generation of a potassium diffusion potential), and by passive, carrier-mediated lactose efflux. We show that in all three cases the number of binding sites is temperature dependent. Binding is maximal and constant above 20 degrees ; it decreases between 20 degrees and 10 degrees . Oxidation of substrate (D-lactate) leads to the development of an electrochemical gradient of protons across the membrane (interior negative and alkaline), which is composed of interconvertible electrical and chemical gradients. We show that both the electrical potential across the membrane and the chemical difference in proton concentrations across the membrane are independent of temperature between 5 degrees and 25 degrees . We show that the number of binding sites induced by D-lactate oxidation depends on pH. At both 25 degrees and 5 degrees , the number of binding sites increases from pH 5 to pH 6.5, remains constant between pH 6.5 and 7, and decreases from pH 7 to pH 8. In contrast, the number of binding sites induced by passive, carrier-mediated lactose efflux is independent of pH between pH 5.5 and pH 8. From these findings, we conclude that the pH- and temperature-dependent effects on the number of 6'-(N-dansyl)aminohexyl-1-beta-thio-D-galactopyranoside binding sites have different origins. The pH dependence of binding is energy linked and reflects in part the pH dependence of the electrochemical gradient of protons across the membrane generated by substrate oxidation. The temperature dependence is not an energy-linked phenomenon. The decrease of the number of binding sites at low temperature probably reflects the aggregation of the lac carrier protein with other membrane proteins. This aggregation takes place as a consequence of the conformational disorder-to-order transition of the membrane lipids and the concomitant preferential segregation of the lac carrier protein in the membrane domains containing the disordered lipids.", "contents": "Functional lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli: temperature and pH dependence of dansyl-galactoside binding. 6'-(N-Dansyl)aminohexyl-1-thio-beta-D-galactopyranoside binds specifically to the lac carrier protein in cytoplasmic membrane vesicles isolated from Escherichia coli. Binding can be induced by substrate oxidation (generation of an electrochemical gradient of protons), by potassium efflux in the presence of valinomycin (generation of a potassium diffusion potential), and by passive, carrier-mediated lactose efflux. We show that in all three cases the number of binding sites is temperature dependent. Binding is maximal and constant above 20 degrees ; it decreases between 20 degrees and 10 degrees . Oxidation of substrate (D-lactate) leads to the development of an electrochemical gradient of protons across the membrane (interior negative and alkaline), which is composed of interconvertible electrical and chemical gradients. We show that both the electrical potential across the membrane and the chemical difference in proton concentrations across the membrane are independent of temperature between 5 degrees and 25 degrees . We show that the number of binding sites induced by D-lactate oxidation depends on pH. At both 25 degrees and 5 degrees , the number of binding sites increases from pH 5 to pH 6.5, remains constant between pH 6.5 and 7, and decreases from pH 7 to pH 8. In contrast, the number of binding sites induced by passive, carrier-mediated lactose efflux is independent of pH between pH 5.5 and pH 8. From these findings, we conclude that the pH- and temperature-dependent effects on the number of 6'-(N-dansyl)aminohexyl-1-beta-thio-D-galactopyranoside binding sites have different origins. The pH dependence of binding is energy linked and reflects in part the pH dependence of the electrochemical gradient of protons across the membrane generated by substrate oxidation. The temperature dependence is not an energy-linked phenomenon. The decrease of the number of binding sites at low temperature probably reflects the aggregation of the lac carrier protein with other membrane proteins. This aggregation takes place as a consequence of the conformational disorder-to-order transition of the membrane lipids and the concomitant preferential segregation of the lac carrier protein in the membrane domains containing the disordered lipids."}
{"id": "PMID:30085", "title": "A macromolecular transducer as illustrated by trout hemoglobin IV.", "content": "Oxygen binding by trout Hb IV has been investigated as a function of pH up to 10 atmospheres (1 MPa) of pure O2. The results bring out an extreme proton-oxygen linkage, which gives rise to a Root effect. They are discussed in relation to the function of the hemoglobin as an oxygen pump. The system is of special interest as providing a prototype of a macromolecule acting as a transducer by coupling two allosterically linked reactions.", "contents": "A macromolecular transducer as illustrated by trout hemoglobin IV. Oxygen binding by trout Hb IV has been investigated as a function of pH up to 10 atmospheres (1 MPa) of pure O2. The results bring out an extreme proton-oxygen linkage, which gives rise to a Root effect. They are discussed in relation to the function of the hemoglobin as an oxygen pump. The system is of special interest as providing a prototype of a macromolecule acting as a transducer by coupling two allosterically linked reactions."}
{"id": "PMID:30082", "title": "[Multicomponent system of specific estrogen-binding liver proteins. Some properties of a rapidly dissociating estrogen-binding liver protein from guinea pigs].", "content": "A study was made of some binding and physico-chemical properties of a special estrogen-binding protein of liver cytozol in sexually mature female and male guinea pigs following its partial purification by means of ammonium sulfate sedimentation, gelfiltration and ion-exchange chromatography. The given protein proved to bind estradiol (E2) with Ka of the 10(7) M-1 order and possessed a rather marked hormonal affinity specificity. Under unbalanced conditions its complexes with E2 were capable of rapid dissociation. Characteristics of the size of protein molecules were: molecular weight--about 60000, Stokes' radius--3.2 nm, sedimentation coefficient--4.6, friction coefficient ratio--1.18. Protein E2-binding activity was reversibly depressed in the presence of high salt concentrations, decreased in the presence of dithioerythritol and on heating at the temperature of over 50 degree C. The optimum E2 binding was observed at pH 7.3--7.7. There were no significant differences in the properties of protein from the liver of males and females. A conclusion was drawn on a close similarity between the given protein of guinea pigs and of a special estrogen-binding protein of the liver in male rats detected by the authors earlier.", "contents": "[Multicomponent system of specific estrogen-binding liver proteins. Some properties of a rapidly dissociating estrogen-binding liver protein from guinea pigs]. A study was made of some binding and physico-chemical properties of a special estrogen-binding protein of liver cytozol in sexually mature female and male guinea pigs following its partial purification by means of ammonium sulfate sedimentation, gelfiltration and ion-exchange chromatography. The given protein proved to bind estradiol (E2) with Ka of the 10(7) M-1 order and possessed a rather marked hormonal affinity specificity. Under unbalanced conditions its complexes with E2 were capable of rapid dissociation. Characteristics of the size of protein molecules were: molecular weight--about 60000, Stokes' radius--3.2 nm, sedimentation coefficient--4.6, friction coefficient ratio--1.18. Protein E2-binding activity was reversibly depressed in the presence of high salt concentrations, decreased in the presence of dithioerythritol and on heating at the temperature of over 50 degree C. The optimum E2 binding was observed at pH 7.3--7.7. There were no significant differences in the properties of protein from the liver of males and females. A conclusion was drawn on a close similarity between the given protein of guinea pigs and of a special estrogen-binding protein of the liver in male rats detected by the authors earlier."}
{"id": "PMID:30086", "title": "Coated vesicles: characterization, selective dissociation, and reassembly.", "content": "Sodium dodecyl sulfate/polyacrylamide gels of coated vesicles from porcine brain (mean 76% coated vesicles) show three major proteins (180,000, 125,000, and 55,000 daltons) that account for 73% of the total protein. Preparations consisting predominantly of coats (65%) have less of the 55,000-dalton protein. Clathrin (180,000 daltons) comprises 40% of the protein of a coated vesicle. Conditions of 2 M urea, 0.25 M MgCl2, or pH 7.5 disrupt the coat and solubilize clathrin. Solubilized clathrin reforms coat structures after dilution of urea or MgCl2. High-pH-solubilized clathrin reassembles after dialysis against buffer at pH 6.5 containing dithiothreitol (5 mM). Reassembled coats are predominantly clathrin.", "contents": "Coated vesicles: characterization, selective dissociation, and reassembly. Sodium dodecyl sulfate/polyacrylamide gels of coated vesicles from porcine brain (mean 76% coated vesicles) show three major proteins (180,000, 125,000, and 55,000 daltons) that account for 73% of the total protein. Preparations consisting predominantly of coats (65%) have less of the 55,000-dalton protein. Clathrin (180,000 daltons) comprises 40% of the protein of a coated vesicle. Conditions of 2 M urea, 0.25 M MgCl2, or pH 7.5 disrupt the coat and solubilize clathrin. Solubilized clathrin reforms coat structures after dilution of urea or MgCl2. High-pH-solubilized clathrin reassembles after dialysis against buffer at pH 6.5 containing dithiothreitol (5 mM). Reassembled coats are predominantly clathrin."}
{"id": "PMID:30087", "title": "Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line.", "content": "We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor.", "contents": "Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line. We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor."}
{"id": "PMID:30092", "title": "Kainic acid and synaptic transmission in the stellate ganglion of the squid.", "content": "Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.", "contents": "Kainic acid and synaptic transmission in the stellate ganglion of the squid. Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse."}
{"id": "PMID:30093", "title": "Structural correlates of recurrent collateral interneurons producing both electrical and chemical inhibitions of the Mauthner cell.", "content": "Intracellular injections of horseradish peroxidase provided a basis for morphological identification of inhibitory interneurons belonging to the recurrent collateral network of the Mauthner cell. Their axons dilate to form unusually large bulbs surrounding the axon cap. The morphological appearance of these bulbs as well as intracellular recordings at their level indicate that they behave as nodes and serve as a final source of current for electrical inhibition of the Mauthner cell. The axon of each interneuron gives rise to two different groups of fibres which are respectively fitted for the mediation of electrical and chemical inhibitions of their target cell.", "contents": "Structural correlates of recurrent collateral interneurons producing both electrical and chemical inhibitions of the Mauthner cell. Intracellular injections of horseradish peroxidase provided a basis for morphological identification of inhibitory interneurons belonging to the recurrent collateral network of the Mauthner cell. Their axons dilate to form unusually large bulbs surrounding the axon cap. The morphological appearance of these bulbs as well as intracellular recordings at their level indicate that they behave as nodes and serve as a final source of current for electrical inhibition of the Mauthner cell. The axon of each interneuron gives rise to two different groups of fibres which are respectively fitted for the mediation of electrical and chemical inhibitions of their target cell."}
{"id": "PMID:30095", "title": "Brain catecholamines metabolism in offspring of amphetamine treated rats.", "content": "Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed.", "contents": "Brain catecholamines metabolism in offspring of amphetamine treated rats. Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed."}
{"id": "PMID:30096", "title": "Role of neuroleptic agents on mouse pulmonary cyclic nucleotide systems.", "content": "The norepinephrine (NE)-induced accumulation of cyclic AMP in incubated tissue slices of mouse lung was inhibited by chlorpromazine (CPZ) and to a lesser extent by haloperidol. In particulate lung fractions both agents blocked dopamine-sensitive adenylate cyclase to a greater degree than the NE-responsive enzyme. Again CPZ was more potent than haloperidol. Acute injections (1/2--8h) of the neuroleptics usually resulted in lower steady state levels of pulmonary cyclic AMP and cyclic GMP following rapid (0.5 sec) tissue inactivation by microwave irradiation. On a subchronic injection schedule, the in vivo levels of pulmonary cyclic AMP tended to increase.", "contents": "Role of neuroleptic agents on mouse pulmonary cyclic nucleotide systems. The norepinephrine (NE)-induced accumulation of cyclic AMP in incubated tissue slices of mouse lung was inhibited by chlorpromazine (CPZ) and to a lesser extent by haloperidol. In particulate lung fractions both agents blocked dopamine-sensitive adenylate cyclase to a greater degree than the NE-responsive enzyme. Again CPZ was more potent than haloperidol. Acute injections (1/2--8h) of the neuroleptics usually resulted in lower steady state levels of pulmonary cyclic AMP and cyclic GMP following rapid (0.5 sec) tissue inactivation by microwave irradiation. On a subchronic injection schedule, the in vivo levels of pulmonary cyclic AMP tended to increase."}
{"id": "PMID:30098", "title": "[Planning of psychotropic drug trials. Statistical evaluation. Hypotheses and methods].", "content": "Any reasonable evaluation presupposes a precise question. Furthermore it is necessary to eliminate all factors of disturbance, which are able either to simulate or to mask a result of evaluation. The most important of these factors is the psychiatrist himself. Therefore, experimental designs have to taken in account the factor psychiatrist. Criteria of the effects of any drug must be relevant with regard to comparison of two or more drug effects. The reproduciability of criteria is very desirable, but a wish-fulfilment under the most circumstances. Because criteria should be independent and mutually exclusive, all scales like the Hamiltons one are not suitable for evaluation. Finally one should use as few criteria as possible. Models of evaluation are described for the most frequent questions in connection with clinical trials in psychopharmacology.", "contents": "[Planning of psychotropic drug trials. Statistical evaluation. Hypotheses and methods]. Any reasonable evaluation presupposes a precise question. Furthermore it is necessary to eliminate all factors of disturbance, which are able either to simulate or to mask a result of evaluation. The most important of these factors is the psychiatrist himself. Therefore, experimental designs have to taken in account the factor psychiatrist. Criteria of the effects of any drug must be relevant with regard to comparison of two or more drug effects. The reproduciability of criteria is very desirable, but a wish-fulfilment under the most circumstances. Because criteria should be independent and mutually exclusive, all scales like the Hamiltons one are not suitable for evaluation. Finally one should use as few criteria as possible. Models of evaluation are described for the most frequent questions in connection with clinical trials in psychopharmacology."}
{"id": "PMID:30099", "title": "Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy \"placebo reactors\" and nonreactors.", "content": "For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with \"placebo reactors\" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as \"placebo reactors\". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively \"placebo reactors\" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from \"reactors\".", "contents": "Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy \"placebo reactors\" and nonreactors. For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with \"placebo reactors\" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as \"placebo reactors\". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively \"placebo reactors\" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from \"reactors\"."}
{"id": "PMID:30100", "title": "[Further developments of the AMP-system. A report on the 2nd AMP-symposium and training seminar (author's transl)].", "content": "This is a report of a symposium and training seminar of the \"Arbeitsgemeinschaft f\u00fcr Methodik und Dokumentation in der Psychiatrie\" (AMP). Video-recordings of two psychiatric interviews were shown during the seminar and rated by the participants using the AMP-3-Scale (Psychopathology). Aim of the seminar was a rater training and the preparation of an expert standard rating. These videotapes with the corresponding standard ratings will enable the different clinics using the AMP-System to compare their rating behaviour. The process of achieving an expert standard rating is described. The training seminar was followed by a symposium during which a series of lectures was presented on \"Standardized Assessment in Psychiatry\", The different working groups of the Association reported about their work and future prospects of the Association were discussed.", "contents": "[Further developments of the AMP-system. A report on the 2nd AMP-symposium and training seminar (author's transl)]. This is a report of a symposium and training seminar of the \"Arbeitsgemeinschaft f\u00fcr Methodik und Dokumentation in der Psychiatrie\" (AMP). Video-recordings of two psychiatric interviews were shown during the seminar and rated by the participants using the AMP-3-Scale (Psychopathology). Aim of the seminar was a rater training and the preparation of an expert standard rating. These videotapes with the corresponding standard ratings will enable the different clinics using the AMP-System to compare their rating behaviour. The process of achieving an expert standard rating is described. The training seminar was followed by a symposium during which a series of lectures was presented on \"Standardized Assessment in Psychiatry\", The different working groups of the Association reported about their work and future prospects of the Association were discussed."}
{"id": "PMID:30101", "title": "Indication of an antipsychotic action of the opiate antagonist naloxone.", "content": "In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded.", "contents": "Indication of an antipsychotic action of the opiate antagonist naloxone. In 20 psychotic patients with frequent hallucinations and/or actual delusional experience a possible antipsychotic action of the opiate antagonist naloxone (N-allyl-noroxymorphone) was investigated, using a double-blind placebo-controlled cross-over design. 18 of these patients were not treated with neuroleptic drugs; 13 suffered from an acute episode of schizophrenia. Psychopathological changes were assessed by the use of the IMPS-scale and of a symptom-specific rating scale (VBS). Intravenous injection of naloxone (in most cases 4.0 mg) induced a reduction of psychotic symptomatology (especially hallucinations) in the majority of patients. Compared with placebo this effect reached statistical significance within 2-7 hours after injection. From this result a possible involvement of endogenous ligands of opiate receptors in the pathogenesis of schizophrenia may be concluded."}
{"id": "PMID:30103", "title": "[Influence of the Benzodiazepine-derivative Ro 06-9098/000 on choreo-athetotic syndromes (author's transl)].", "content": "Five patients suffering from choreo-athetotic syndromes of different genesis were treated with the benzodiazepine-derivative Ro 06-9098/000 (7-Nitro-1(methylmethoxy)-1,3-dihydro-5-phenyl-2 H-1,4-benzodiazepin-2-one). The existing hyperkinesias could be well influenced in four cases of male patients, sufficiently in one case of a female patient. The sedative effect, accompanied by a muscle hypotonia appearing simultaneously under the medication, did not represent and essential limiting factors at the chosen dose of 5--20 mg/die. The observed successes in therapy point at the result and effect of benzodiazepine derivatives on extra-pyramidalmotoric hyperkinesias which got little attention until now.", "contents": "[Influence of the Benzodiazepine-derivative Ro 06-9098/000 on choreo-athetotic syndromes (author's transl)]. Five patients suffering from choreo-athetotic syndromes of different genesis were treated with the benzodiazepine-derivative Ro 06-9098/000 (7-Nitro-1(methylmethoxy)-1,3-dihydro-5-phenyl-2 H-1,4-benzodiazepin-2-one). The existing hyperkinesias could be well influenced in four cases of male patients, sufficiently in one case of a female patient. The sedative effect, accompanied by a muscle hypotonia appearing simultaneously under the medication, did not represent and essential limiting factors at the chosen dose of 5--20 mg/die. The observed successes in therapy point at the result and effect of benzodiazepine derivatives on extra-pyramidalmotoric hyperkinesias which got little attention until now."}
{"id": "PMID:30105", "title": "[The preprogramming of behavior patterns by changing the neurotransmitter metabolism in the early postnatal ontogenesis of albino rats].", "content": "Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability.", "contents": "[The preprogramming of behavior patterns by changing the neurotransmitter metabolism in the early postnatal ontogenesis of albino rats]. Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability."}
{"id": "PMID:30106", "title": "The striatonigral fibres and the feedback control of dopamine metabolism.", "content": "It proved possible to make lesions which interrupted the striatonigral GABA-containing pathway in the rat brain without causing concomitant damage to the nigrostriatal dopamine containing system. Estimations of striatal concentrations of dopamine (DA), dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) inducated that these lesions had no influence either on normal striatal DA turnover or on the enhancement of DA turnover induced by neuroleptics. Behavioural experiments suggested a motor output function for the striatonigral pathway.", "contents": "The striatonigral fibres and the feedback control of dopamine metabolism. It proved possible to make lesions which interrupted the striatonigral GABA-containing pathway in the rat brain without causing concomitant damage to the nigrostriatal dopamine containing system. Estimations of striatal concentrations of dopamine (DA), dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) inducated that these lesions had no influence either on normal striatal DA turnover or on the enhancement of DA turnover induced by neuroleptics. Behavioural experiments suggested a motor output function for the striatonigral pathway."}
{"id": "PMID:30110", "title": "Benzodiazepines and behavioral effects of reward (water) omission in the rat.", "content": "Two behaviors related to nonreward (omission of water in an enclosure where the rats were habituated to drink) were studied. The time spent licking the bottles during water omission and the time spent drinking during a subsequent 5-min drinking session (water available) were recorded. The drinking session was performed 30 min after the water-omission session. Rats subjected to water omission showed an enhanced drinking time that varied with the length of the water omission session, with the motivational state of the animals, and with the previous number of water-omission sessions. Diazepam, chlordiazepoxide, lorazepam, and meprobamate (i.p., 30 min before water omission), increased the time spent licking the empty bottles, but failed to abolish subsequently enhanced drinking. However, some of our data suggested that minor tranquilizers weakly reduced the increased drinking induced by nonreward, despite their direct stimulation on water drinking. It is proposed that either minor tranquilizers are devoid of general antifrustration activity or nonreward-induced frustration and nonreward-induced drive enhancement may not be correlated.", "contents": "Benzodiazepines and behavioral effects of reward (water) omission in the rat. Two behaviors related to nonreward (omission of water in an enclosure where the rats were habituated to drink) were studied. The time spent licking the bottles during water omission and the time spent drinking during a subsequent 5-min drinking session (water available) were recorded. The drinking session was performed 30 min after the water-omission session. Rats subjected to water omission showed an enhanced drinking time that varied with the length of the water omission session, with the motivational state of the animals, and with the previous number of water-omission sessions. Diazepam, chlordiazepoxide, lorazepam, and meprobamate (i.p., 30 min before water omission), increased the time spent licking the empty bottles, but failed to abolish subsequently enhanced drinking. However, some of our data suggested that minor tranquilizers weakly reduced the increased drinking induced by nonreward, despite their direct stimulation on water drinking. It is proposed that either minor tranquilizers are devoid of general antifrustration activity or nonreward-induced frustration and nonreward-induced drive enhancement may not be correlated."}
{"id": "PMID:30115", "title": "Pulmonary complications associated with the prune-belly syndrome.", "content": "Eight patients are presented who demonstrate many of the pulmonary complications seen in the prune-belly syndrome. The patients are divided into two major groups: Group I includes pulmonary hypoplasia; Group II includes lobar atelectasis and pneumonia. The etiology, pathogenesis, and radiographic features of these complications are discussed. Pulmonary complications become more important as renal dialysis and transplantation spare more of these patients from an early uremic death. Prompt recognition of the type and the extent of pulmonary disease in patients with the prune-belly syndrome may lead to increased survival.", "contents": "Pulmonary complications associated with the prune-belly syndrome. Eight patients are presented who demonstrate many of the pulmonary complications seen in the prune-belly syndrome. The patients are divided into two major groups: Group I includes pulmonary hypoplasia; Group II includes lobar atelectasis and pneumonia. The etiology, pathogenesis, and radiographic features of these complications are discussed. Pulmonary complications become more important as renal dialysis and transplantation spare more of these patients from an early uremic death. Prompt recognition of the type and the extent of pulmonary disease in patients with the prune-belly syndrome may lead to increased survival."}
{"id": "PMID:30119", "title": "Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice.", "content": "Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed.", "contents": "Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice. Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed."}
{"id": "PMID:30122", "title": "Effect of beta-fluorophenethylamine analogs on monoamine oxidase substrate preference.", "content": "A novel potentiometric assay was employed to evaluate the effects of beta-fluorination of phenethylamine (PEA) on brain MAO substrate preference. Through the use of the substrate selective MAO inhibitors clorgyline (type A) and Deprenyl (type B), F-PEA and F2-PEA were found to be preferred substrates for MAO type B. Since various degrees of fluorination of the parent PEA molecule proportionally decrease the pKa values, as well as their substrate activity for MAO, it is suggested that the protonated form of PEA and its respective mono and difluoro analogs are the preferred substrate forms for catalysis by brain MAO.", "contents": "Effect of beta-fluorophenethylamine analogs on monoamine oxidase substrate preference. A novel potentiometric assay was employed to evaluate the effects of beta-fluorination of phenethylamine (PEA) on brain MAO substrate preference. Through the use of the substrate selective MAO inhibitors clorgyline (type A) and Deprenyl (type B), F-PEA and F2-PEA were found to be preferred substrates for MAO type B. Since various degrees of fluorination of the parent PEA molecule proportionally decrease the pKa values, as well as their substrate activity for MAO, it is suggested that the protonated form of PEA and its respective mono and difluoro analogs are the preferred substrate forms for catalysis by brain MAO."}
{"id": "PMID:30123", "title": "Survival of Leptospira interrogans serovar pomona in an acidic soil under simulated New Zealand field conditions.", "content": "Leptospira interrogans serovar pomona was found to survive for at least 42 days in a typical New Zealand soil under simulated winter field conditions. The soil was markedly acidic with a pH of 5.5 and survival times were not reduced even when its water content was only 23%. The values of both these parameters are considerably less than previously recorded for the survival of leptospires in soil. Two methods were used to recover leptospires from the soil microflora. One was the culture of a membrane filtrate in EMJH media with or without contaminant-suppressing additives and the other was the direct inoculation of soil-washings into hamsters. Both techniques proved to equally sensitive. It was estimated that following the addition of 5 X 10(8) leptospires to the soil samples less than 2 X 10(4) were present after six weeks.", "contents": "Survival of Leptospira interrogans serovar pomona in an acidic soil under simulated New Zealand field conditions. Leptospira interrogans serovar pomona was found to survive for at least 42 days in a typical New Zealand soil under simulated winter field conditions. The soil was markedly acidic with a pH of 5.5 and survival times were not reduced even when its water content was only 23%. The values of both these parameters are considerably less than previously recorded for the survival of leptospires in soil. Two methods were used to recover leptospires from the soil microflora. One was the culture of a membrane filtrate in EMJH media with or without contaminant-suppressing additives and the other was the direct inoculation of soil-washings into hamsters. Both techniques proved to equally sensitive. It was estimated that following the addition of 5 X 10(8) leptospires to the soil samples less than 2 X 10(4) were present after six weeks."}
{"id": "PMID:30124", "title": "Tissue and blood distribution of gamma-glutamyl transferase in the lamb and in the ewe.", "content": "Gamma-glutamyl transferase distribution was studied in 10 ewes and 10 lambs; in both groups kidney was the most active organ, followed by pancreas, liver and lungs. In kidney and liver, GGT was bound mainly to cellular structures. Blood GGT activity of 48 lambs was 44 +/- 11 iu/litre and 33 +/- 7 iu/litre of 45 ewes.", "contents": "Tissue and blood distribution of gamma-glutamyl transferase in the lamb and in the ewe. Gamma-glutamyl transferase distribution was studied in 10 ewes and 10 lambs; in both groups kidney was the most active organ, followed by pancreas, liver and lungs. In kidney and liver, GGT was bound mainly to cellular structures. Blood GGT activity of 48 lambs was 44 +/- 11 iu/litre and 33 +/- 7 iu/litre of 45 ewes."}
{"id": "PMID:30125", "title": "Subcellular fractionation studies on peroral jejunal biopsies from the dog.", "content": "Portions of closed jejunal biopsies from the dog were homogenised and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles were determined using highly sensitive assay procedures. The following organelles, with assayed marker enzymes and modal densities between brackets were characterised: peroxisomes (catalase, 1.21); brush borders (zinc-resistant alpha-glucosidase, leucyl-beta-naphthyl-amidase, gamma-glutamyl transferase, alkaline phosphatase, 1.20); lysosomes (N-acetyl-beta-glucosaminidase, alpha-mannosidase, 1.19); mitochondria (malate dehydrogenase, 1.18); endoplasmic reticulum (Tris-resistant alpha-glucosidase, 1.16); basal-lateral membranes (5'-nucleotidase, 1.11) and cytosol (lactate dehydrogenase). Homogenisation in isotonic sucrose containing digitonin (0.12 mmol/litre) selectively disrupted lysosomes and increased the equilibrium density of brush border and basal-lateral membranes. This procedure will be used to study the subcellular pathology of naturally occurring intestinal disease in the dog.", "contents": "Subcellular fractionation studies on peroral jejunal biopsies from the dog. Portions of closed jejunal biopsies from the dog were homogenised and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles were determined using highly sensitive assay procedures. The following organelles, with assayed marker enzymes and modal densities between brackets were characterised: peroxisomes (catalase, 1.21); brush borders (zinc-resistant alpha-glucosidase, leucyl-beta-naphthyl-amidase, gamma-glutamyl transferase, alkaline phosphatase, 1.20); lysosomes (N-acetyl-beta-glucosaminidase, alpha-mannosidase, 1.19); mitochondria (malate dehydrogenase, 1.18); endoplasmic reticulum (Tris-resistant alpha-glucosidase, 1.16); basal-lateral membranes (5'-nucleotidase, 1.11) and cytosol (lactate dehydrogenase). Homogenisation in isotonic sucrose containing digitonin (0.12 mmol/litre) selectively disrupted lysosomes and increased the equilibrium density of brush border and basal-lateral membranes. This procedure will be used to study the subcellular pathology of naturally occurring intestinal disease in the dog."}
{"id": "PMID:30128", "title": "Gill ventilation in the sturgeon, Acipenser transmontanus: unusual adaptations for bottom dwelling.", "content": "Measurements of branchial cavity water pressures and flow patterns, arterial blood PO2 and pH, and oxygen utilization and uptake have been made in undisturbed, free swimming sturgeon, Acipenser transmontanus. Although the jaws are degenerate and the oral apparatus is highly modified for feeding, gill ventilation is nonetheless powered by a buccal force pump and an opercular suction pump common to most bony fishes. The reduced spiracles play little or no role in gill ventilation. In sturgeon in which water intake through the ventrally located mouth was experimentally eliminated, a condition which may often develop when these fish forage in mud and sand on river substrates, effective ventilation of the gills was maintained with water drawn into the branchial cavities in a retrograde fashion solely through permanent openings in the upper regions of the opercular slits. O2 uptake and transport also remained at control levels. It is suggested that this unusual alternative mode of gill ventilation in the sturgeon represents an important respiratory adaptation to bottom dwelling and feeding.", "contents": "Gill ventilation in the sturgeon, Acipenser transmontanus: unusual adaptations for bottom dwelling. Measurements of branchial cavity water pressures and flow patterns, arterial blood PO2 and pH, and oxygen utilization and uptake have been made in undisturbed, free swimming sturgeon, Acipenser transmontanus. Although the jaws are degenerate and the oral apparatus is highly modified for feeding, gill ventilation is nonetheless powered by a buccal force pump and an opercular suction pump common to most bony fishes. The reduced spiracles play little or no role in gill ventilation. In sturgeon in which water intake through the ventrally located mouth was experimentally eliminated, a condition which may often develop when these fish forage in mud and sand on river substrates, effective ventilation of the gills was maintained with water drawn into the branchial cavities in a retrograde fashion solely through permanent openings in the upper regions of the opercular slits. O2 uptake and transport also remained at control levels. It is suggested that this unusual alternative mode of gill ventilation in the sturgeon represents an important respiratory adaptation to bottom dwelling and feeding."}
{"id": "PMID:30129", "title": "Hemoglobin-ligand interaction in fetal and maternal sheep blood.", "content": "Hemoglobin-ligand interaction was studied in maternal and fetal sheep blood as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of NaOH or HCl at constant PCO2 (fixed acid Bohr effect). For maternal blood, CO2 Bohr factor was -0.41 at 50% oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. For fetal blood, CO2 Bohr factor was -0.45 at 50% oxygen saturation, unchanging at lower saturation and decreasing in magnitude at higher saturation. Fixed acid Bohr factor was relatively saturation independent with a value of -0.36 for fetal blood and -0.27 for maternal blood. The pH-independent effect of molecular CO2 on oxygen affinity was markedly saturation dependent being greatest at low oxygen saturation. The CO2 effect was greater in maternal blood than fetal blood. However, the magnitude of the saturation dependency of Bohr factor is not great enough to have major physiological significance in oxygen transfer across the sheep placenta.", "contents": "Hemoglobin-ligand interaction in fetal and maternal sheep blood. Hemoglobin-ligand interaction was studied in maternal and fetal sheep blood as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of NaOH or HCl at constant PCO2 (fixed acid Bohr effect). For maternal blood, CO2 Bohr factor was -0.41 at 50% oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. For fetal blood, CO2 Bohr factor was -0.45 at 50% oxygen saturation, unchanging at lower saturation and decreasing in magnitude at higher saturation. Fixed acid Bohr factor was relatively saturation independent with a value of -0.36 for fetal blood and -0.27 for maternal blood. The pH-independent effect of molecular CO2 on oxygen affinity was markedly saturation dependent being greatest at low oxygen saturation. The CO2 effect was greater in maternal blood than fetal blood. However, the magnitude of the saturation dependency of Bohr factor is not great enough to have major physiological significance in oxygen transfer across the sheep placenta."}
{"id": "PMID:30130", "title": "Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude.", "content": "At high altitude, in resting conditions, no differences have been observed between High Altitude Natives (HAN) and acclimatized Sea Level Natives (SLN) in AaDO2, aADCO2 or venous admixture. In acclimatized SLN, AaDO2 is smaller than at sea level because of: (1) The minor effect on arterial oxygenation of the probably constant venous admixture. (2) The reduction of VA/Q inequality as shown by a smaller aADCO2. In HAN, DLCO is greater than in SLN; the contribution of DM or VC in this difference remains unsettled, mainly because of the difficulties of measurement of DM and VC in HAN suddenly exposed to acute hyperoxia. In SLN, in acute hypoxia, DLCO increased transitorily. Asynchronous mechanisms of adaptation to high altitude are evoked.", "contents": "Pulmonary gas exchange, diffusing capacity in natives and newcomers at high altitude. At high altitude, in resting conditions, no differences have been observed between High Altitude Natives (HAN) and acclimatized Sea Level Natives (SLN) in AaDO2, aADCO2 or venous admixture. In acclimatized SLN, AaDO2 is smaller than at sea level because of: (1) The minor effect on arterial oxygenation of the probably constant venous admixture. (2) The reduction of VA/Q inequality as shown by a smaller aADCO2. In HAN, DLCO is greater than in SLN; the contribution of DM or VC in this difference remains unsettled, mainly because of the difficulties of measurement of DM and VC in HAN suddenly exposed to acute hyperoxia. In SLN, in acute hypoxia, DLCO increased transitorily. Asynchronous mechanisms of adaptation to high altitude are evoked."}
{"id": "PMID:30131", "title": "Oxygen affinity in the blood of sheep.", "content": "The oxygen affinity in the blood of adult Dorset sheep with HbB was studied by determining several oxygen equilibrium curves under different conditions of pH and PCO2 by a method that allowed strict control of pH, PCO2, and HCO3- concentration over the entire curve. Nomograms and equations were derived that allowed the estimation of the oxygen saturation in a sample of blood in the range 0 to 100%, either from pH, PCO2 and PO2, or from PO2 and known P50. The advantage of this approach is that no assumptions about the shape of the oxygen equilibrium curve need be made (i.e. the Hill parameter, n, is not required to be constant), since the entire curve was measured.", "contents": "Oxygen affinity in the blood of sheep. The oxygen affinity in the blood of adult Dorset sheep with HbB was studied by determining several oxygen equilibrium curves under different conditions of pH and PCO2 by a method that allowed strict control of pH, PCO2, and HCO3- concentration over the entire curve. Nomograms and equations were derived that allowed the estimation of the oxygen saturation in a sample of blood in the range 0 to 100%, either from pH, PCO2 and PO2, or from PO2 and known P50. The advantage of this approach is that no assumptions about the shape of the oxygen equilibrium curve need be made (i.e. the Hill parameter, n, is not required to be constant), since the entire curve was measured."}
{"id": "PMID:30163", "title": "Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes.", "content": "A modified analytical isoelectric focusing procedure on polyacrylamide gel slabs, offering increased resolving capacity, has been developed for identification of six subtypes of the most common alpha-1-antitrypsin (A-1-AT) phenotype, Pi M. Combination of commercial Ampholine and other ampoteric substances, so called separators, produces pH plateaus, determined by the properties of the the additatives. Equilibrium is reached after extended focusing time, whereby stabilization of A-1-AT through alkylation is advantagous. The significance of this high resolution method for applications of the Pi system in genetic studies, and the general relevance of the modifications for other analytical purposes are discussed. A new nomenclature recommendation is presented.", "contents": "Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes. A modified analytical isoelectric focusing procedure on polyacrylamide gel slabs, offering increased resolving capacity, has been developed for identification of six subtypes of the most common alpha-1-antitrypsin (A-1-AT) phenotype, Pi M. Combination of commercial Ampholine and other ampoteric substances, so called separators, produces pH plateaus, determined by the properties of the the additatives. Equilibrium is reached after extended focusing time, whereby stabilization of A-1-AT through alkylation is advantagous. The significance of this high resolution method for applications of the Pi system in genetic studies, and the general relevance of the modifications for other analytical purposes are discussed. A new nomenclature recommendation is presented."}
{"id": "PMID:30164", "title": "Purification and properties of human amniotic fluid diamine oxidase.", "content": "Diamine oxidase (DAO) was purified from amniotic fluid. The activity was separated in two DAO fractions with pI values of 5.8 and 4.0. Molecular weight were found to be 245,000 and 485,000, respectively, with subunit molecular weight of 110,000. This indicated that they probably are dimer and tetramer of the same DAO subunit. The enzyme was active against putrescine and histamine and was strongly inhibited by carbonyl group reagents. A Ping Pong Bi Ter enzyme reaction mechanism is probable. The diamine, with one amino group protonized, is suggested to be responsible for interaction with the enzyme.", "contents": "Purification and properties of human amniotic fluid diamine oxidase. Diamine oxidase (DAO) was purified from amniotic fluid. The activity was separated in two DAO fractions with pI values of 5.8 and 4.0. Molecular weight were found to be 245,000 and 485,000, respectively, with subunit molecular weight of 110,000. This indicated that they probably are dimer and tetramer of the same DAO subunit. The enzyme was active against putrescine and histamine and was strongly inhibited by carbonyl group reagents. A Ping Pong Bi Ter enzyme reaction mechanism is probable. The diamine, with one amino group protonized, is suggested to be responsible for interaction with the enzyme."}
{"id": "PMID:30165", "title": "Determination of plasma or serum haemoglobin by peroxidase activity employing 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen.", "content": "A procedure is described for the determination of plasma or serum haemoglobin employing the peroxidase activity of the haemoprotein using 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. The method gives equal results for free haemoglobin, methaemoglobin and haemoglobin complexed to haptoglobin. It is designed to measure haemoglobin in the range 0--12 mumol/l. The peroxidase activity of myoglobin is similar to that of haemoglobin, whereas haemin in free solution, bound to haemopexin or to albumin (methaemalbumin) shows much lower activity. The precision within run is satisfactory, +/- 5%.", "contents": "Determination of plasma or serum haemoglobin by peroxidase activity employing 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. A procedure is described for the determination of plasma or serum haemoglobin employing the peroxidase activity of the haemoprotein using 2,2'-azino-di-(3-ethyl-benzthiazolinsulphonate-6) as chromogen. The method gives equal results for free haemoglobin, methaemoglobin and haemoglobin complexed to haptoglobin. It is designed to measure haemoglobin in the range 0--12 mumol/l. The peroxidase activity of myoglobin is similar to that of haemoglobin, whereas haemin in free solution, bound to haemopexin or to albumin (methaemalbumin) shows much lower activity. The precision within run is satisfactory, +/- 5%."}
{"id": "PMID:30173", "title": "Viruses and bacteria associated with acute respiratory illnesses in young children in general practice.", "content": "The results obtained and the laboratory methods used for the isolation of viruses and bacteria from Malaysian children with acute respiratory illnesses seen in a private clinic are described. Of the 65 children studied virus isolations were obtained from 26 children, bacteria from 10 and both virus and bacteria from another 5. The agents isolated were influenza viruses, parainfluenza viruses, adenoviruses, Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus pyogenes.", "contents": "Viruses and bacteria associated with acute respiratory illnesses in young children in general practice. The results obtained and the laboratory methods used for the isolation of viruses and bacteria from Malaysian children with acute respiratory illnesses seen in a private clinic are described. Of the 65 children studied virus isolations were obtained from 26 children, bacteria from 10 and both virus and bacteria from another 5. The agents isolated were influenza viruses, parainfluenza viruses, adenoviruses, Bordetella pertussis, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus pyogenes."}
{"id": "PMID:30178", "title": "Current concepts of the undescended testis.", "content": "Abnormalities of testicular descent represent the most common genitourinary anomaly in men. Many aspects of testicular maldescent remain controversial. The etiology of the undescended testis is still not known, but results of experimental work in rats strongly support the hormonal theories. Distinction between the truly undescended testis and the retractile testis remains a problem, making retrospective analysis of previous data confusing. Newer aspects of diagnosis of nonpalpable testes include the human chorionic gonadotropin test, herniography, venography and arteriography. Routine aspects of surgical therapy have changed little in recent years, although newer techniques, such as microsurgical procedures and innovative scrotal anchoring methods, are now available. Malignant tumors and infertility are the most worrisome complications. Evidence is presented to suggest that prognosis is related not only to choice of therapy but also to its timing. The recent evidence for Sertoli cell dysfunction, if substantiated may resolve some of the controversies.", "contents": "Current concepts of the undescended testis. Abnormalities of testicular descent represent the most common genitourinary anomaly in men. Many aspects of testicular maldescent remain controversial. The etiology of the undescended testis is still not known, but results of experimental work in rats strongly support the hormonal theories. Distinction between the truly undescended testis and the retractile testis remains a problem, making retrospective analysis of previous data confusing. Newer aspects of diagnosis of nonpalpable testes include the human chorionic gonadotropin test, herniography, venography and arteriography. Routine aspects of surgical therapy have changed little in recent years, although newer techniques, such as microsurgical procedures and innovative scrotal anchoring methods, are now available. Malignant tumors and infertility are the most worrisome complications. Evidence is presented to suggest that prognosis is related not only to choice of therapy but also to its timing. The recent evidence for Sertoli cell dysfunction, if substantiated may resolve some of the controversies."}
{"id": "PMID:30183", "title": "Takayasu's disease: association with HLA-B5.", "content": "The frequency of HLA-B5 (66%, n = 38) in Japanese patients with Takayasu's disease was significantly higher than in controls (32%, n = 160). The level of significance was x2 = 13.53, P less than 0.0005 and corrected P less than 0.009.", "contents": "Takayasu's disease: association with HLA-B5. The frequency of HLA-B5 (66%, n = 38) in Japanese patients with Takayasu's disease was significantly higher than in controls (32%, n = 160). The level of significance was x2 = 13.53, P less than 0.0005 and corrected P less than 0.009."}
{"id": "PMID:30190", "title": "The lethal effects of the cibarial and pharyngeal armatures of mosquitoes on microfilariae.", "content": "Microfilariae of Wuchereria bancrofti and Brugia pahangi were killed by the chewing action of the cibarial and pharyngeal armatures and other papillae and spines in the fore-gut of mosquitoes. The proportion of ingested microfilariae that were killed was largely dependent on the presence and shape of the cibarial armature. Anopheles farauti No. 1 and Anopheles gambiae species A and B have well developed cibarial armatures and killed 36 to 96% of the ingested microfilariae. Culex pipiens fatigans has a poorly developed cibarial armature and killed only 6% of the microfilariae. Aedes aegypti and Aedes togoi lack cibarial armatures but have the remaining fore-gut structures. They killed only 2 to 22% of the microfilariae. The significance of these observations in relation to the control of filariasis with diethylcarbamazine is discussed.", "contents": "The lethal effects of the cibarial and pharyngeal armatures of mosquitoes on microfilariae. Microfilariae of Wuchereria bancrofti and Brugia pahangi were killed by the chewing action of the cibarial and pharyngeal armatures and other papillae and spines in the fore-gut of mosquitoes. The proportion of ingested microfilariae that were killed was largely dependent on the presence and shape of the cibarial armature. Anopheles farauti No. 1 and Anopheles gambiae species A and B have well developed cibarial armatures and killed 36 to 96% of the ingested microfilariae. Culex pipiens fatigans has a poorly developed cibarial armature and killed only 6% of the microfilariae. Aedes aegypti and Aedes togoi lack cibarial armatures but have the remaining fore-gut structures. They killed only 2 to 22% of the microfilariae. The significance of these observations in relation to the control of filariasis with diethylcarbamazine is discussed."}
{"id": "PMID:30192", "title": "Mouse Peyer's patches contain T cells capable of inducing the graft-versus-host reaction (GVHR).", "content": "The potential of cells from the Peyer's patches (PP) of normal adult DBA/2 Tru mice (DBA/2) to induce a graft-versus-host reaction when injected into (C57BL/6 Tru x  DBA/2 Tru)F1 hybrid (B6D2F1) mice was studied. The injection of 10(6) to 10(7) DBA/2 PP or spleen cells i.p. into neonatal F1 mice produced a striking splenomegaly. Comparable doses of parental PP or spleen cells injected into a rear footpad of adult F1 mice also induced a marked enlargement of the draining popliteal lymph node. In addition, PP cells were also capable of producing a lethal runting syndrome when injected i.v. into sublethally irradiated adult F1 recipients. In all assays, injection of syngeneic B6D2F1 cells had little or no effect. Treatment of the DBA/2 PP cells with anti-theta serum and complement abolished their capacity to induce splenomegaly in neonatal F1 mice. The graft-versus-host reaction activity of the PP cells could also be eliminated by thymus deprivation of the donor DBA/2 mice. These data are contradictory to previous findings in which it was observed that mouse PP cells were unable to induce graft-versus-host reaction.", "contents": "Mouse Peyer's patches contain T cells capable of inducing the graft-versus-host reaction (GVHR). The potential of cells from the Peyer's patches (PP) of normal adult DBA/2 Tru mice (DBA/2) to induce a graft-versus-host reaction when injected into (C57BL/6 Tru x  DBA/2 Tru)F1 hybrid (B6D2F1) mice was studied. The injection of 10(6) to 10(7) DBA/2 PP or spleen cells i.p. into neonatal F1 mice produced a striking splenomegaly. Comparable doses of parental PP or spleen cells injected into a rear footpad of adult F1 mice also induced a marked enlargement of the draining popliteal lymph node. In addition, PP cells were also capable of producing a lethal runting syndrome when injected i.v. into sublethally irradiated adult F1 recipients. In all assays, injection of syngeneic B6D2F1 cells had little or no effect. Treatment of the DBA/2 PP cells with anti-theta serum and complement abolished their capacity to induce splenomegaly in neonatal F1 mice. The graft-versus-host reaction activity of the PP cells could also be eliminated by thymus deprivation of the donor DBA/2 mice. These data are contradictory to previous findings in which it was observed that mouse PP cells were unable to induce graft-versus-host reaction."}
{"id": "PMID:30194", "title": "ABO-incompatible marrow transplants.", "content": "Seventeen patients with aplastic anemia or acute leukemia received transplants from donors who had major ABO incompatibilities. Antibody titers were decreased by plasma and whole blood exchanges prior to marrow infusion. All 17 patients were successfully engrafted, and there was one possible rejection in the patient with the highest pretransplant anti-A IgG titer. Nine of 17 patients are currently alive. A review was carried out of transplants performed in Seattle between HLA-matched siblings with aplastic anemia and leukemia. Two hundred forty-six evaluable patients with ABO-compatible donors were compared with 46 with minor ABO-incompatible donors. There was no effect of minor ABO incompatibility on graft rejection, incidence and severity of graft-versus-host disease, or survival.", "contents": "ABO-incompatible marrow transplants. Seventeen patients with aplastic anemia or acute leukemia received transplants from donors who had major ABO incompatibilities. Antibody titers were decreased by plasma and whole blood exchanges prior to marrow infusion. All 17 patients were successfully engrafted, and there was one possible rejection in the patient with the highest pretransplant anti-A IgG titer. Nine of 17 patients are currently alive. A review was carried out of transplants performed in Seattle between HLA-matched siblings with aplastic anemia and leukemia. Two hundred forty-six evaluable patients with ABO-compatible donors were compared with 46 with minor ABO-incompatible donors. There was no effect of minor ABO incompatibility on graft rejection, incidence and severity of graft-versus-host disease, or survival."}
{"id": "PMID:30195", "title": "Lipoprotein-lipase activity in subcutaneous, adipose tissue in healthy subjects: variation of activity in a population of 60-year-old men.", "content": "The lipoprotein-lipase activity (LPLA) in the abdominal, subcutaneous, adipose tissue was studied in a random sample (n = 69) of 60-year-old men. A new method for the quantification of LPLA was applied. The mean value was 67 mU/g when expressed per gram (wet weight) of adipose tissue. Several subjects within the lower part of the range of adipose-tissue LPLA values had low concentrations of serum-triglycerides (S-TG). There was no correlation between the LPLA and S-TG concentrations in the fasting state. Among the 69 subjects, four had newly detected diabetes mellitus and had significantly lower LPLA in the adipose tissue than the control group. The fat-cell size and the LPLA per gram of adipose tissue were not correlated. Thus, obesity without diabetes mellitus does not imply a low LPLA concentration in adipose tissue. The variation of the concentration of adipose-tissue LPLA in the fasting state in this population was explained only to a minor extent by the variation of S-insulin and blood-glucose parameters, when analysed statistically by a stepwise multiple-regression technique.", "contents": "Lipoprotein-lipase activity in subcutaneous, adipose tissue in healthy subjects: variation of activity in a population of 60-year-old men. The lipoprotein-lipase activity (LPLA) in the abdominal, subcutaneous, adipose tissue was studied in a random sample (n = 69) of 60-year-old men. A new method for the quantification of LPLA was applied. The mean value was 67 mU/g when expressed per gram (wet weight) of adipose tissue. Several subjects within the lower part of the range of adipose-tissue LPLA values had low concentrations of serum-triglycerides (S-TG). There was no correlation between the LPLA and S-TG concentrations in the fasting state. Among the 69 subjects, four had newly detected diabetes mellitus and had significantly lower LPLA in the adipose tissue than the control group. The fat-cell size and the LPLA per gram of adipose tissue were not correlated. Thus, obesity without diabetes mellitus does not imply a low LPLA concentration in adipose tissue. The variation of the concentration of adipose-tissue LPLA in the fasting state in this population was explained only to a minor extent by the variation of S-insulin and blood-glucose parameters, when analysed statistically by a stepwise multiple-regression technique."}
{"id": "PMID:30196", "title": "Postpubertal untreated cryptorchidism. Anatomical relationship between Leydig cells and tubular sclerosis.", "content": "A histological study of the postpubertal untreated cryptorchid testis establishes a direct anatomical relationship between Leydig cells and tubular sclerosis, an age-related process ranging from mild fibrosis of the tubular tunica propria to complete tubular hyalinization. Two separate processes are involved. Mild or moderate tunical fibrosis is related to pretubular hyperplastic Leydig cell nodules, while severe tubular sclerosis and hyalinization depends on the development of intratunical Leydig cells, a finding hitherto undescribed. More probing studies are needed to define the mechanisms whereby these abnormal Leydig cells cause tubular tunical fibrosis.", "contents": "Postpubertal untreated cryptorchidism. Anatomical relationship between Leydig cells and tubular sclerosis. A histological study of the postpubertal untreated cryptorchid testis establishes a direct anatomical relationship between Leydig cells and tubular sclerosis, an age-related process ranging from mild fibrosis of the tubular tunica propria to complete tubular hyalinization. Two separate processes are involved. Mild or moderate tunical fibrosis is related to pretubular hyperplastic Leydig cell nodules, while severe tubular sclerosis and hyalinization depends on the development of intratunical Leydig cells, a finding hitherto undescribed. More probing studies are needed to define the mechanisms whereby these abnormal Leydig cells cause tubular tunical fibrosis."}
{"id": "PMID:30191", "title": "Reversal of the storage lesion of CPD bank blood: a problem in clinical medicine.", "content": "The effect of phosphate buffer on the course of pH, ATP, and 2,3-PDG of CPD red blood cells stored at three temperatures was observed. Basic phosphate at an equilibrated level of 10 mM (as iP) maintained pH above 7.00 and ATP and 2,3-DPG above 70 per cent of initial value in cells stored at 37 C for 24 hours. In contrast however, at 25 and 4 C no buffering was obtained with basic phosphate concentrations up to 50 mM, but values for both ATP and 2,3-DPG were higher in phosphate treated aliquots than in controls throughout storage. When the pH of blood stored at 4 C was adjusted into the range 7.15 to 7.25 with tromethamine and the level of iP raised to 10 mM by addition of Na2HPO4 on day seven, it was found that ATP and 2,3-DPG levels were maintained at 90 and 120 per cent, while control levels fell to 60 and 12 per cent, respectively at 21 days. The process described parallels the normal repair of damaged red blood cells of bank blood that occurs in vivo following transfusion.", "contents": "Reversal of the storage lesion of CPD bank blood: a problem in clinical medicine. The effect of phosphate buffer on the course of pH, ATP, and 2,3-PDG of CPD red blood cells stored at three temperatures was observed. Basic phosphate at an equilibrated level of 10 mM (as iP) maintained pH above 7.00 and ATP and 2,3-DPG above 70 per cent of initial value in cells stored at 37 C for 24 hours. In contrast however, at 25 and 4 C no buffering was obtained with basic phosphate concentrations up to 50 mM, but values for both ATP and 2,3-DPG were higher in phosphate treated aliquots than in controls throughout storage. When the pH of blood stored at 4 C was adjusted into the range 7.15 to 7.25 with tromethamine and the level of iP raised to 10 mM by addition of Na2HPO4 on day seven, it was found that ATP and 2,3-DPG levels were maintained at 90 and 120 per cent, while control levels fell to 60 and 12 per cent, respectively at 21 days. The process described parallels the normal repair of damaged red blood cells of bank blood that occurs in vivo following transfusion."}
{"id": "PMID:30197", "title": "Alpha-blockers and urethral pressure in neurological patients.", "content": "In 11 patients with upper motor neuron bladder paresis due to spinal trauma, 2 patients with lower motor neuron bladder paresis, and 4 patients with multiple sclerosis, alpha-adrenergic blockade with 10 mg Regitine intravenously decreased the maximum urethral closure pressure to an average of 42%. The decrease was most pronounced in a patient with lower motor neuron bladder paresis and a flaccid pelvic floor. Treatment with phenoxybenzamine was found valuable in patients with multiple sclerosis and poor bladder emptying as well as in patients with lower motor neuron bladder paresis. In patients with detrusorsphincter dyssynergia this treatment was of no value.", "contents": "Alpha-blockers and urethral pressure in neurological patients. In 11 patients with upper motor neuron bladder paresis due to spinal trauma, 2 patients with lower motor neuron bladder paresis, and 4 patients with multiple sclerosis, alpha-adrenergic blockade with 10 mg Regitine intravenously decreased the maximum urethral closure pressure to an average of 42%. The decrease was most pronounced in a patient with lower motor neuron bladder paresis and a flaccid pelvic floor. Treatment with phenoxybenzamine was found valuable in patients with multiple sclerosis and poor bladder emptying as well as in patients with lower motor neuron bladder paresis. In patients with detrusorsphincter dyssynergia this treatment was of no value."}
{"id": "PMID:30198", "title": "Detrusor hyperreflexia in female urinary incontinence treated pharmacologically.", "content": "Detrusor hyperreflexia was found in 54 patients or 14.6% of 369 consecutive patients referred for urinary incontinence and/or genital prolapse during a 2-year period. The dominant symptom was urge incontinence. The urological investigation consisted of a medium fill water cystometry in the supine position. 20 patients (37%) suffered from cerebral or pyramidal nervous disorders. The treatment of choice was pharmacological with parasympatholytica, methantheline bromide (Banthine). The follow-up examinations performed in 33 patients after 6 months treatment showed an improvement rate of 82%. The importance of performing a cystometry in all female patients referred for urinary incontinence is stressed.", "contents": "Detrusor hyperreflexia in female urinary incontinence treated pharmacologically. Detrusor hyperreflexia was found in 54 patients or 14.6% of 369 consecutive patients referred for urinary incontinence and/or genital prolapse during a 2-year period. The dominant symptom was urge incontinence. The urological investigation consisted of a medium fill water cystometry in the supine position. 20 patients (37%) suffered from cerebral or pyramidal nervous disorders. The treatment of choice was pharmacological with parasympatholytica, methantheline bromide (Banthine). The follow-up examinations performed in 33 patients after 6 months treatment showed an improvement rate of 82%. The importance of performing a cystometry in all female patients referred for urinary incontinence is stressed."}
{"id": "PMID:30199", "title": "Effect of beta-adrenoceptor stimulation on the human bladder in vivo.", "content": "The effect of beta-adrenoceptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated into. Terbutaline, a selective beta2-receptor-stimulating agent, was tested in 9 persons and isoprenaline, a general beta-receptor-stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average around 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%.", "contents": "Effect of beta-adrenoceptor stimulation on the human bladder in vivo. The effect of beta-adrenoceptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated into. Terbutaline, a selective beta2-receptor-stimulating agent, was tested in 9 persons and isoprenaline, a general beta-receptor-stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average around 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%."}
{"id": "PMID:30200", "title": "Effects of beta-adrenergic stimulating and blocking agents on the dynamics of the human bladder outlet.", "content": "The alpha-adrenergic innervation of the functional urethra is a well-known fact, while beta-adrenergic influence is rather unknown until now. We studied the influence of beta-stimulating and beta-blocking agents on the human urethra by the urethral pressure profile (UPP). A decrease of the UPP under orciprenaline sulfate and an increase under propranolol could be mentioned.", "contents": "Effects of beta-adrenergic stimulating and blocking agents on the dynamics of the human bladder outlet. The alpha-adrenergic innervation of the functional urethra is a well-known fact, while beta-adrenergic influence is rather unknown until now. We studied the influence of beta-stimulating and beta-blocking agents on the human urethra by the urethral pressure profile (UPP). A decrease of the UPP under orciprenaline sulfate and an increase under propranolol could be mentioned."}
{"id": "PMID:30202", "title": "Twenty-five-year experience with prune belly syndrome.", "content": "Thirty cases of prune belly syndrome with no stillborn deaths seen over a twenty-five-year period at a university pediatric hospital are reviewed and the management, findings, and prognosis discussed.", "contents": "Twenty-five-year experience with prune belly syndrome. Thirty cases of prune belly syndrome with no stillborn deaths seen over a twenty-five-year period at a university pediatric hospital are reviewed and the management, findings, and prognosis discussed."}
{"id": "PMID:30203", "title": "Urinary tract reconstruction in prune belly syndrome.", "content": "Fifteen boys with prune belly syndrome cared for over a ten-year period required surgical treatment because of uncontrolled infection and/or progressive azotemia. Five died of renal dysplasia. Primary or staged reconstruction resulted in significant improvement when ureteral reimplantation was combined with tailoring of ureteral caliber.", "contents": "Urinary tract reconstruction in prune belly syndrome. Fifteen boys with prune belly syndrome cared for over a ten-year period required surgical treatment because of uncontrolled infection and/or progressive azotemia. Five died of renal dysplasia. Primary or staged reconstruction resulted in significant improvement when ureteral reimplantation was combined with tailoring of ureteral caliber."}
{"id": "PMID:30216", "title": "[Age-dependent adaptation of erythrocytes in the model of haemoglobinolysis (author's transl)].", "content": "1. The erythrocyte is suitable as a model of investigating the mechanism of  adaptation as a function of aging. 2. By hemolysis experiments in isotonic solutions of various pH-values changes of the resistance of human erythrocytes during the mechanism of aging in the organism are established. 3. In isotonic alkaline solutions the resistance of the human erythrocytes changes according to the \"curve of vitability\" of the human organism.", "contents": "[Age-dependent adaptation of erythrocytes in the model of haemoglobinolysis (author's transl)]. 1. The erythrocyte is suitable as a model of investigating the mechanism of  adaptation as a function of aging. 2. By hemolysis experiments in isotonic solutions of various pH-values changes of the resistance of human erythrocytes during the mechanism of aging in the organism are established. 3. In isotonic alkaline solutions the resistance of the human erythrocytes changes according to the \"curve of vitability\" of the human organism."}
{"id": "PMID:30211", "title": "[Effect of low temperatures on the functional state of the membranes of the hepatic endoplasmic reticulum].", "content": "Oxidation of fluorescent substrates--NADPH and 4-dimethylamine chalcone (DMC) by microsomes from liver endoplasmic reticulum was studied after freezing and thawing of these cells organelles. Slow freezing to -25 degrees or quick freezing to -196 degrees did not affect distinctly the rate of NADPH oxidation after thawing, but oxidation of DMC by microsomes was decreased in both cases. Freezing and subsequent thawing of microsomes impaired apparently the terminal sites of electron transfer and/or the systems of hydroxylation, including cytochrome P-450. Slow freezing to -25 degrees impaired microsomes more markedly than quick freezing to -196 degrees.", "contents": "[Effect of low temperatures on the functional state of the membranes of the hepatic endoplasmic reticulum]. Oxidation of fluorescent substrates--NADPH and 4-dimethylamine chalcone (DMC) by microsomes from liver endoplasmic reticulum was studied after freezing and thawing of these cells organelles. Slow freezing to -25 degrees or quick freezing to -196 degrees did not affect distinctly the rate of NADPH oxidation after thawing, but oxidation of DMC by microsomes was decreased in both cases. Freezing and subsequent thawing of microsomes impaired apparently the terminal sites of electron transfer and/or the systems of hydroxylation, including cytochrome P-450. Slow freezing to -25 degrees impaired microsomes more markedly than quick freezing to -196 degrees."}
{"id": "PMID:30212", "title": "[Concentration of cyclic nucleotides, activity of adenylate cyclase, 3',5'-AMP phosphodiesterase and guanylate cyclase in plasma membranes from liver and hepatomas of different degrees of malignancy].", "content": "Adenylate cyclase activity as well as intracellular content of sAMP were decreased 2.5-4-fold, as compared with normal state, in plasmatic membranes (PM) of hepatoma 22 and of Ehrlich ascites carcinoma--the tumors characterized by high level- of malignancy. Activity of cAMP phosphodiesterase exceeded distinctly the normal value in all the tumors studied. In less malignant hepatoma 48 the adenylate cyclase activity and content of cAMP were similar to those found in normal liver cells. The guanylate cyclase activity did not differ markedly from values found in normal liver cells in PM of all the tumors studied and in liver tissue of the tumor-bearing animals. Distinct alterations were not found in content of cGMP in the tumors, except of hepatomas 60 and 22, in which the nucleotide level exceeded 2-fold the normal value. The ratio cAMP/cGMP was decreased in the most malignant tumors. At the same time, the ratio was distinctly elevated in tumors with the middle level of malignancy (hepatomas 60 and 61).", "contents": "[Concentration of cyclic nucleotides, activity of adenylate cyclase, 3',5'-AMP phosphodiesterase and guanylate cyclase in plasma membranes from liver and hepatomas of different degrees of malignancy]. Adenylate cyclase activity as well as intracellular content of sAMP were decreased 2.5-4-fold, as compared with normal state, in plasmatic membranes (PM) of hepatoma 22 and of Ehrlich ascites carcinoma--the tumors characterized by high level- of malignancy. Activity of cAMP phosphodiesterase exceeded distinctly the normal value in all the tumors studied. In less malignant hepatoma 48 the adenylate cyclase activity and content of cAMP were similar to those found in normal liver cells. The guanylate cyclase activity did not differ markedly from values found in normal liver cells in PM of all the tumors studied and in liver tissue of the tumor-bearing animals. Distinct alterations were not found in content of cGMP in the tumors, except of hepatomas 60 and 22, in which the nucleotide level exceeded 2-fold the normal value. The ratio cAMP/cGMP was decreased in the most malignant tumors. At the same time, the ratio was distinctly elevated in tumors with the middle level of malignancy (hepatomas 60 and 61)."}
{"id": "PMID:30219", "title": "[Lipids and lipoproteins in early changes of arteriosclerosis].", "content": "LDL, fibrinogen and other plasma macromolecules are retained in intima in substantial amounts. In areas where lipid is accumulating a large part of LDL is immobilized possibily by binding to fibrin. Lipid may be deposited from LDL as a result of degradation by a cathepsin in intima.", "contents": "[Lipids and lipoproteins in early changes of arteriosclerosis]. LDL, fibrinogen and other plasma macromolecules are retained in intima in substantial amounts. In areas where lipid is accumulating a large part of LDL is immobilized possibily by binding to fibrin. Lipid may be deposited from LDL as a result of degradation by a cathepsin in intima."}
{"id": "PMID:30220", "title": "[The coincidence of visceral lupus erythematosus and epilepsy].", "content": "It is reported on course and problems of the diagnosis of a lupus erythematodes visceralis with epilepsy. In the demonstrated case the initial stage was characterized by the nearly simultaneous appearance of relapsing arthritides and epilepsy. The diagnosis was made in the stage of an acute exacerbation with cardiac symptomatology which began after the medicamentous treatment with diphenylhydantoin. Up to this moment an oligosymptomatic lupus erythematodes visceralis had not yet been diagnosed. Anamnestic data and the laboratory-clinical findings of the further course of the disease proved the actual lupus erythematodes visceralis. It is referred to the necessity of an aimed anamnesis and a determination of the antinuclear factors before every application ofhydantoin derivations when an epilepsy and joint symptomatology are present.", "contents": "[The coincidence of visceral lupus erythematosus and epilepsy]. It is reported on course and problems of the diagnosis of a lupus erythematodes visceralis with epilepsy. In the demonstrated case the initial stage was characterized by the nearly simultaneous appearance of relapsing arthritides and epilepsy. The diagnosis was made in the stage of an acute exacerbation with cardiac symptomatology which began after the medicamentous treatment with diphenylhydantoin. Up to this moment an oligosymptomatic lupus erythematodes visceralis had not yet been diagnosed. Anamnestic data and the laboratory-clinical findings of the further course of the disease proved the actual lupus erythematodes visceralis. It is referred to the necessity of an aimed anamnesis and a determination of the antinuclear factors before every application ofhydantoin derivations when an epilepsy and joint symptomatology are present."}
{"id": "PMID:30228", "title": "[GLC-data of 19 hydrolysis-derivatives rised from 12 important benzodiazepines and 17 main-metabolites (author's transl)].", "content": "Analytical investigations of extracts after acid hydrolysis are in use especially considering benzodiazepine screening methods. The article describes the gas-chromatographic data of 19 hydrolysis-derivatives which are formed by hydrolysis of 12 important 1,4- and 1,5-benzodiazepines and 17 main metabolites.", "contents": "[GLC-data of 19 hydrolysis-derivatives rised from 12 important benzodiazepines and 17 main-metabolites (author's transl)]. Analytical investigations of extracts after acid hydrolysis are in use especially considering benzodiazepine screening methods. The article describes the gas-chromatographic data of 19 hydrolysis-derivatives which are formed by hydrolysis of 12 important 1,4- and 1,5-benzodiazepines and 17 main metabolites."}
{"id": "PMID:30245", "title": "[Use of phenazepam in the treatment of neurotic conditions].", "content": "The report contains data concerning clinical studies of a new Soviet tranquilizer of benzodiazepine derivative--phenazepam. Treatment of 100 patients gave a good therapeutical effect in 82%. The best results were attained in the treatment of generalized hystero-neurotical states, somewhat less in the group of neurotic states with a prevalence of affective disorders and the less effective in the obsessive-phobic syndrome. On the basis of comparative studies, the conclusion is made that phenazepam is not worse by its psychotropic activity than ativan (lorazepam) and exceeds diazepam (seduxen), most likely because of its myorelaxing action. The drug exerted an expressed hypnotic effect being not less than eunoctin and other eunectics.", "contents": "[Use of phenazepam in the treatment of neurotic conditions]. The report contains data concerning clinical studies of a new Soviet tranquilizer of benzodiazepine derivative--phenazepam. Treatment of 100 patients gave a good therapeutical effect in 82%. The best results were attained in the treatment of generalized hystero-neurotical states, somewhat less in the group of neurotic states with a prevalence of affective disorders and the less effective in the obsessive-phobic syndrome. On the basis of comparative studies, the conclusion is made that phenazepam is not worse by its psychotropic activity than ativan (lorazepam) and exceeds diazepam (seduxen), most likely because of its myorelaxing action. The drug exerted an expressed hypnotic effect being not less than eunoctin and other eunectics."}
{"id": "PMID:30246", "title": "Cytochrome P-450 and alkane hydroxylase activity in Candida guilliermondii.", "content": "In the investigated Candida guilliermondii strain after growth on n-alkanes as the only carbon and energy source 5--10 nMol cytochrome P-450 per g cells (wet weight) could be detected. Cytochrome P-450 and alkane hydroxylase activity was found in the 100 000 xg pellet. Cofactor studies and inhibition experiments revealed the existence of a NADPH-dependent cytochrome P-450 alkane hydroxylase system.", "contents": "Cytochrome P-450 and alkane hydroxylase activity in Candida guilliermondii. In the investigated Candida guilliermondii strain after growth on n-alkanes as the only carbon and energy source 5--10 nMol cytochrome P-450 per g cells (wet weight) could be detected. Cytochrome P-450 and alkane hydroxylase activity was found in the 100 000 xg pellet. Cofactor studies and inhibition experiments revealed the existence of a NADPH-dependent cytochrome P-450 alkane hydroxylase system."}
{"id": "PMID:30247", "title": "Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs.", "content": "Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity.", "contents": "Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs. Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity."}
{"id": "PMID:30248", "title": "Comparison between the unsaturated plasma folate binder and in vivo labelled plasma folate binder.", "content": "Endogenous plasma folate binder denuded of folate by dialysis at pH 3, subsequently bound more methylfolate than folic acid, in contrast with the minor unsaturated plasma binder which bound folic acid in preference to methylfolate. On Sephadex DEAE-A50 chromatography 14C-CH3H4PteGlu bound to acid-denuded endogenous binder, eluted like the endogenous binder-radioactivity, labelled in vivo after oral 14C-CH3H4PteGlu. It is suggested that the endogenous plasma folate binder is not identical with the unsaturated binder.", "contents": "Comparison between the unsaturated plasma folate binder and in vivo labelled plasma folate binder. Endogenous plasma folate binder denuded of folate by dialysis at pH 3, subsequently bound more methylfolate than folic acid, in contrast with the minor unsaturated plasma binder which bound folic acid in preference to methylfolate. On Sephadex DEAE-A50 chromatography 14C-CH3H4PteGlu bound to acid-denuded endogenous binder, eluted like the endogenous binder-radioactivity, labelled in vivo after oral 14C-CH3H4PteGlu. It is suggested that the endogenous plasma folate binder is not identical with the unsaturated binder."}
{"id": "PMID:30249", "title": "Peripheral platelet count in response to salbutamol before and after adrenergic beta-receptor blockade.", "content": "The effect of salbutamol (a comparatively selective adrenergic beta2-receptor agonist) on the peripheral platelet concentration was studied before and after the ingestion of either 50 mg metoprolol or 40 mg propranolol. The study was carried out on healthy males volunteers and autologous 51Cr-labelled platelets were employed at the experiments. Salbutamol was infused intravenously over a period of 6 min in a dose of 0.27 microgram.kg(-1). min(-1). Prior to metoprolol and propranolol administration a statistically significant lowering in platelet-bound radioactivity (PBR) was obtained in response to the salbutamol infusions. This salbutamol-induced fall in PBR was completely blocked by propranolol but was left unaffected by metoprolol. It is concluded that adrenergic beta2-receptor stimulation induces a transient lowering of the peripheral platelet count.", "contents": "Peripheral platelet count in response to salbutamol before and after adrenergic beta-receptor blockade. The effect of salbutamol (a comparatively selective adrenergic beta2-receptor agonist) on the peripheral platelet concentration was studied before and after the ingestion of either 50 mg metoprolol or 40 mg propranolol. The study was carried out on healthy males volunteers and autologous 51Cr-labelled platelets were employed at the experiments. Salbutamol was infused intravenously over a period of 6 min in a dose of 0.27 microgram.kg(-1). min(-1). Prior to metoprolol and propranolol administration a statistically significant lowering in platelet-bound radioactivity (PBR) was obtained in response to the salbutamol infusions. This salbutamol-induced fall in PBR was completely blocked by propranolol but was left unaffected by metoprolol. It is concluded that adrenergic beta2-receptor stimulation induces a transient lowering of the peripheral platelet count."}
{"id": "PMID:30250", "title": "Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats.", "content": "Rats with different levels of blood glucose concentration were exposed to 10 min of complete brain ischemia achieved by compression of neck vessels by a pneumatic cuff. All normoglycemic rats survived the ischemic period and made the best clinical recovery. Hyperglycemic rats died within 12 h. Seizure activity was observed in all animals in this group. Three of eight hypoglycemic rats died between 3 and 16 days. The clinical recovery was less complete than in the control group. Thus, recovery from cerebral ischemia depends upon preischemic blood glucose concentration. Hyper- and hypoglycemia hamper the clinical recovery after transient cerebral ischemia.", "contents": "Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats. Rats with different levels of blood glucose concentration were exposed to 10 min of complete brain ischemia achieved by compression of neck vessels by a pneumatic cuff. All normoglycemic rats survived the ischemic period and made the best clinical recovery. Hyperglycemic rats died within 12 h. Seizure activity was observed in all animals in this group. Three of eight hypoglycemic rats died between 3 and 16 days. The clinical recovery was less complete than in the control group. Thus, recovery from cerebral ischemia depends upon preischemic blood glucose concentration. Hyper- and hypoglycemia hamper the clinical recovery after transient cerebral ischemia."}
{"id": "PMID:30251", "title": "beta-Glucosidase activities in the Norrbotten type of juvenile Gaucher's disease.", "content": "beta-Glucosidase and N-acetyl-beta-glucosaminidase activities were measured with synthetic substrates in peripheral leucocytes, urine and serum from patients with juvenile type of Gaucher's disease. Our findings in urine and serum make it clear that diagnosis by using synthetic substrate is not possible. In peripheral leucocytes reduced level was found for beta-glucosidase activity in patients with Gaucher's disease but also there occurred some overlapping with controls. The possible explanation to these findings are discussed.", "contents": "beta-Glucosidase activities in the Norrbotten type of juvenile Gaucher's disease. beta-Glucosidase and N-acetyl-beta-glucosaminidase activities were measured with synthetic substrates in peripheral leucocytes, urine and serum from patients with juvenile type of Gaucher's disease. Our findings in urine and serum make it clear that diagnosis by using synthetic substrate is not possible. In peripheral leucocytes reduced level was found for beta-glucosidase activity in patients with Gaucher's disease but also there occurred some overlapping with controls. The possible explanation to these findings are discussed."}
{"id": "PMID:30252", "title": "The effect of stannous fluoride on human plaque acidogenicity in situ (Stephan curve).", "content": "A system employing an Ingold glass electrode was shown to give reliable measurements of pH drops in dental plaque in situ (Stephan curve readings). The system was used to demonstrate that mouthrinses of 0.2 per cent aqueous solutions of stannous fluoride reduced the pH drops markedly for at least seven hours. A reduction of the stannous fluoride concentration increased the pH drops and decreased the duration of the inhibiting effect. A commercial toothpaste containing stannous fluoride and stannous pyrophosphate had an effect similar to the 0.2 per cent mouthrinse. It was shown that tin accumulated in dental plaque after application of solutions containing stannous fluoride. About 40 per cent of the amount of tin present in the plaque immediately after the mouthrinse was still retained seven hours later. It is suggested that the reduction in acid formation may be caused by stannous ions adsorbing to the bacterial cell wall thus disturbing membrane transport mechanisms, or through inhibition of enzyme systems essential in the fermentation of sugars. The observed effect may be a part of the mechanism involved in the caries preventive function of stannous fluoride.", "contents": "The effect of stannous fluoride on human plaque acidogenicity in situ (Stephan curve). A system employing an Ingold glass electrode was shown to give reliable measurements of pH drops in dental plaque in situ (Stephan curve readings). The system was used to demonstrate that mouthrinses of 0.2 per cent aqueous solutions of stannous fluoride reduced the pH drops markedly for at least seven hours. A reduction of the stannous fluoride concentration increased the pH drops and decreased the duration of the inhibiting effect. A commercial toothpaste containing stannous fluoride and stannous pyrophosphate had an effect similar to the 0.2 per cent mouthrinse. It was shown that tin accumulated in dental plaque after application of solutions containing stannous fluoride. About 40 per cent of the amount of tin present in the plaque immediately after the mouthrinse was still retained seven hours later. It is suggested that the reduction in acid formation may be caused by stannous ions adsorbing to the bacterial cell wall thus disturbing membrane transport mechanisms, or through inhibition of enzyme systems essential in the fermentation of sugars. The observed effect may be a part of the mechanism involved in the caries preventive function of stannous fluoride."}
{"id": "PMID:30254", "title": "Observations of otoconial membranes from human infants.", "content": "The microdissection technique was used to study otoconial membrane from 30 human infants ranging from newborn to 2 years of age. Both saccular and utricular membranes were quite variable in overall shape. During the neonatal period, the gelatinous layer of the otoconial membrane appears to thicken and become less adherent to the macular surface than in the fetal period. In many infants older than 6 weeks, otoconial membranes were found at autopsy to be completely dislodged from the maculae, with abnormally large saccular otoconia present in four specimens. Fourteen of the infants studied died of sudden infant death syndrome and 16 died of other causes. The incidence of detached otoconial membranes was approximately the same in both groups. Although the majority of these membranes were apparently dislodged post mortem, the present findings suggest that otoconial membranes are susceptible to pathological alteration due to disease or head trauma.", "contents": "Observations of otoconial membranes from human infants. The microdissection technique was used to study otoconial membrane from 30 human infants ranging from newborn to 2 years of age. Both saccular and utricular membranes were quite variable in overall shape. During the neonatal period, the gelatinous layer of the otoconial membrane appears to thicken and become less adherent to the macular surface than in the fetal period. In many infants older than 6 weeks, otoconial membranes were found at autopsy to be completely dislodged from the maculae, with abnormally large saccular otoconia present in four specimens. Fourteen of the infants studied died of sudden infant death syndrome and 16 died of other causes. The incidence of detached otoconial membranes was approximately the same in both groups. Although the majority of these membranes were apparently dislodged post mortem, the present findings suggest that otoconial membranes are susceptible to pathological alteration due to disease or head trauma."}
{"id": "PMID:30255", "title": "Bacteriology of maxillary sinusitis in relation to quality of the retained secretion.", "content": "The bacteriological findings in 200 patients with acute maxillary sinusitis are reported. It is concluded that the sampling technique--by antral aspiration--is highly significant in the evaluation of the bacteriological background of sinusitis, whereas the anerobic transport of the sample seems to be of less importance. By aspiration the purulent secretion can be properly separated from the non-purulent secretion. Pneumococci, H. influenzae and anaerobic bacteria can be isolated in about 90% of the patients with true sinus empyema, while sterile conditions are rare.", "contents": "Bacteriology of maxillary sinusitis in relation to quality of the retained secretion. The bacteriological findings in 200 patients with acute maxillary sinusitis are reported. It is concluded that the sampling technique--by antral aspiration--is highly significant in the evaluation of the bacteriological background of sinusitis, whereas the anerobic transport of the sample seems to be of less importance. By aspiration the purulent secretion can be properly separated from the non-purulent secretion. Pneumococci, H. influenzae and anaerobic bacteria can be isolated in about 90% of the patients with true sinus empyema, while sterile conditions are rare."}
{"id": "PMID:30261", "title": "Base pairing mRNA-rRNA. The arrangement of nucleotides in the message for coat protein of phage MS 2.", "content": "The relation of the nucleotide sequences in the message and of the short nucleotide sequence in 3' terminus of 16 S ribosomal RNA was found to differ from statistical expectancy. The observation is interpreted in terms of both the ribosomal interactions and the molecular evolution.", "contents": "Base pairing mRNA-rRNA. The arrangement of nucleotides in the message for coat protein of phage MS 2. The relation of the nucleotide sequences in the message and of the short nucleotide sequence in 3' terminus of 16 S ribosomal RNA was found to differ from statistical expectancy. The observation is interpreted in terms of both the ribosomal interactions and the molecular evolution."}
{"id": "PMID:30262", "title": "Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. I. Gel filtration in 6 M guanidine hydrochloride.", "content": "Highly purified glycopolypeptides HA1 and HA2 were separated from bromelain-released haemagglutinin of influenza virus A/Dunedin/4/73 (H3N2) by gel filtration in 6 M guanidine hydrochloride under reducing conditions. The purity of both glycopolypeptides was proved by extensive studies. Despite the lack of C-terminal end, the isolated HA2 glycopolypeptide displayed some hydrophobic properties.", "contents": "Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. I. Gel filtration in 6 M guanidine hydrochloride. Highly purified glycopolypeptides HA1 and HA2 were separated from bromelain-released haemagglutinin of influenza virus A/Dunedin/4/73 (H3N2) by gel filtration in 6 M guanidine hydrochloride under reducing conditions. The purity of both glycopolypeptides was proved by extensive studies. Despite the lack of C-terminal end, the isolated HA2 glycopolypeptide displayed some hydrophobic properties."}
{"id": "PMID:30263", "title": "UV-inactivation of Epstein-Barr virus: differences in early antigen expression in two different non-productive cell lines and influence of caffeine.", "content": "Two non-productive Epstein-Barr (EB) virus genome-carrying lymphoblastoid cell lines, namely Raji and NC37, were used for studying the effect of UV irradiation on the ability of P3HR-1 EB virus to induce early antigen (EA) formation. In NC37 cells infected with UV-irradiated virus the formation of EA was delayed; thus the slope of inactivation curve based on the early (24 hr) reading was steeper than that based on the late (72 hr) reading. This was not observed in Raji cells. Caffeine did not influence the percentage of EA positive cells in cultures infected with untreated virus; however, the drug exhibited a marked inhibitory effect on EA production after infection with UV-irradiated virus. The sensitivity to caffeine effect decreased more rapidly with time after infection of Raji than of NC37 cells, suggesting a higher degree of readiness of the host cell repair system in the former than in the latter cells. The caffeine effect was merely directed against the synthesis of R (restricted) component of EA; its influence on the D (diffuse) component formation was negligible.", "contents": "UV-inactivation of Epstein-Barr virus: differences in early antigen expression in two different non-productive cell lines and influence of caffeine. Two non-productive Epstein-Barr (EB) virus genome-carrying lymphoblastoid cell lines, namely Raji and NC37, were used for studying the effect of UV irradiation on the ability of P3HR-1 EB virus to induce early antigen (EA) formation. In NC37 cells infected with UV-irradiated virus the formation of EA was delayed; thus the slope of inactivation curve based on the early (24 hr) reading was steeper than that based on the late (72 hr) reading. This was not observed in Raji cells. Caffeine did not influence the percentage of EA positive cells in cultures infected with untreated virus; however, the drug exhibited a marked inhibitory effect on EA production after infection with UV-irradiated virus. The sensitivity to caffeine effect decreased more rapidly with time after infection of Raji than of NC37 cells, suggesting a higher degree of readiness of the host cell repair system in the former than in the latter cells. The caffeine effect was merely directed against the synthesis of R (restricted) component of EA; its influence on the D (diffuse) component formation was negligible."}
{"id": "PMID:30264", "title": "Suppression of an arenavirus by a togavirus in experimental acute double infection.", "content": "Lymphocytic choriomeningitis virus (LCMV) and tick-borne encephalitis virus (TEV) were inoculated in young and old chick embryo cell (CEC) and in L-cell cultures at various multiplicities per cell, simultaneously or 17 hr apart. The yield of infective LCMV was inhibited in double infection, most in old CEC with elevated interferon mechanisms, and least in L cells producing no interferon. In young CEC, TEV-induced interferon was stimulated by coinfecting LCMV; LCMV alone never has induced interferon. The reproduction of TEV was little affected. In doubly infected L cells the fluorescent antibody techniques revealed more cells positive for each viral antigen than in single infections, but the yield of LCMV per one antigen-positive cell was decreased. The course of TEV infection in cerebrally infected mice was not changed by co-infection with LCMV. The titre of LCMV in the brains of doubly infected mice was markedly suppressed when compared with LCMV monoinfection. High interferon levels in brains of all mice infected with TEV were not affected by LCMV co-infection.", "contents": "Suppression of an arenavirus by a togavirus in experimental acute double infection. Lymphocytic choriomeningitis virus (LCMV) and tick-borne encephalitis virus (TEV) were inoculated in young and old chick embryo cell (CEC) and in L-cell cultures at various multiplicities per cell, simultaneously or 17 hr apart. The yield of infective LCMV was inhibited in double infection, most in old CEC with elevated interferon mechanisms, and least in L cells producing no interferon. In young CEC, TEV-induced interferon was stimulated by coinfecting LCMV; LCMV alone never has induced interferon. The reproduction of TEV was little affected. In doubly infected L cells the fluorescent antibody techniques revealed more cells positive for each viral antigen than in single infections, but the yield of LCMV per one antigen-positive cell was decreased. The course of TEV infection in cerebrally infected mice was not changed by co-infection with LCMV. The titre of LCMV in the brains of doubly infected mice was markedly suppressed when compared with LCMV monoinfection. High interferon levels in brains of all mice infected with TEV were not affected by LCMV co-infection."}
{"id": "PMID:30265", "title": "Variations in biological properties of geographic strains of western equine encephalomyelitis virus before and after passage in Culex tarsalis and Culiseta melanura.", "content": "Western equine encephalomyelitis (WEE) virus strains from the eastern and western United States were compared using two biological markers: antigenic properties measured by cross complement fixation (CF) tests and the size of plaques produced in Vero cell cultures. Slight antigenic differences were discernible on a geographic basis, and all of the virus strains from the West produced significantly larger plaques than the eastern isolates. One virus strain from each region was serially passaged in Culex tarsalis and Culiseta melanura by intrathoracic inoculation. No change in plaque size was detected as a result of mosquito passage. After passage of the eastern strain of WEE virus in C. tarsalis, its mouse brain CF antigen titer was increased to resemble the high CF antigen titer produced by the western strain. However, the antisera titers did not change when tested with this antigen. A cross plaque reduction neutralization test (PRNT) with the two virus strains before and after passage in mosquitoes failed to reveal any antigenic changes.", "contents": "Variations in biological properties of geographic strains of western equine encephalomyelitis virus before and after passage in Culex tarsalis and Culiseta melanura. Western equine encephalomyelitis (WEE) virus strains from the eastern and western United States were compared using two biological markers: antigenic properties measured by cross complement fixation (CF) tests and the size of plaques produced in Vero cell cultures. Slight antigenic differences were discernible on a geographic basis, and all of the virus strains from the West produced significantly larger plaques than the eastern isolates. One virus strain from each region was serially passaged in Culex tarsalis and Culiseta melanura by intrathoracic inoculation. No change in plaque size was detected as a result of mosquito passage. After passage of the eastern strain of WEE virus in C. tarsalis, its mouse brain CF antigen titer was increased to resemble the high CF antigen titer produced by the western strain. However, the antisera titers did not change when tested with this antigen. A cross plaque reduction neutralization test (PRNT) with the two virus strains before and after passage in mosquitoes failed to reveal any antigenic changes."}
{"id": "PMID:30266", "title": "Improved detection by immunodiffusion of type-specific influenza antibody in avian sera.", "content": "Various solvents and kinds of agar and agarose as well as various ribonucleoprotein (RNP) antigen preparations were tested in a search for optimal conditions for the detection of low levels of type-specific influenza antibody in avian sera by gel double diffusion. The best results were obtained with one kind of agarose in a solvent with lowered ionic strength (approx. 0.075 M). A hypertonic solvent usually gave worse or negative results, with the exception of one kind of agarose. In general, agarose yielded better results than agar. The results of immuno-precipitation were affected by the strain of influenza virus used for the preparation of RNP antigen.", "contents": "Improved detection by immunodiffusion of type-specific influenza antibody in avian sera. Various solvents and kinds of agar and agarose as well as various ribonucleoprotein (RNP) antigen preparations were tested in a search for optimal conditions for the detection of low levels of type-specific influenza antibody in avian sera by gel double diffusion. The best results were obtained with one kind of agarose in a solvent with lowered ionic strength (approx. 0.075 M). A hypertonic solvent usually gave worse or negative results, with the exception of one kind of agarose. In general, agarose yielded better results than agar. The results of immuno-precipitation were affected by the strain of influenza virus used for the preparation of RNP antigen."}
{"id": "PMID:30267", "title": "Experimental infection of hare (Lepus europaeus) with Coxiella burnetii and Rickettsia slovaca.", "content": "Hares (Lepus europaeus L.) infected subcutaneously (s.c.) or per os with Coxiella burnetii and s.c. with Rickettsia slovaca overcame an inapparent infection accompanied by irregular rickettsaemia and distribution of rickettsiae to different organs and variable antibody response. Neither riskettsia could be detected in faeces of infected animals, but C. burnetii was found in the urine of one hare, which died on day 13 post infection (p.i.). Antibodies against C. burnetii persisted for one year of observation period, those against R. slovaca up to the 181st day p.i. Based on the results obtained and data on other lagomorph species, the hare could play an important role as host of C. burnetii and R. slovaca in nature.", "contents": "Experimental infection of hare (Lepus europaeus) with Coxiella burnetii and Rickettsia slovaca. Hares (Lepus europaeus L.) infected subcutaneously (s.c.) or per os with Coxiella burnetii and s.c. with Rickettsia slovaca overcame an inapparent infection accompanied by irregular rickettsaemia and distribution of rickettsiae to different organs and variable antibody response. Neither riskettsia could be detected in faeces of infected animals, but C. burnetii was found in the urine of one hare, which died on day 13 post infection (p.i.). Antibodies against C. burnetii persisted for one year of observation period, those against R. slovaca up to the 181st day p.i. Based on the results obtained and data on other lagomorph species, the hare could play an important role as host of C. burnetii and R. slovaca in nature."}
{"id": "PMID:30268", "title": "H-1 and X14 parvovirus antibodies in women with abortions or still-births.", "content": "Antibodies against H-1 and X14 parvoviruses were found 13.71 and 9.14%, respectively, of 350 sera from women affected by repeated abortions or still-births. On the contrary, only 2.66 and 1.66% of 300 control sera were positive to the two viruses. The difference in the incidence of antibodies appears highly significant (p greater than 0.001). Therefore a possible role of the parvoviruses in inducing abortions or still-births in humans is suggested.", "contents": "H-1 and X14 parvovirus antibodies in women with abortions or still-births. Antibodies against H-1 and X14 parvoviruses were found 13.71 and 9.14%, respectively, of 350 sera from women affected by repeated abortions or still-births. On the contrary, only 2.66 and 1.66% of 300 control sera were positive to the two viruses. The difference in the incidence of antibodies appears highly significant (p greater than 0.001). Therefore a possible role of the parvoviruses in inducing abortions or still-births in humans is suggested."}
{"id": "PMID:30271", "title": "Depression: a new approach to an old syndrome.", "content": "Depression is a medical illness related to an interplay of genetic, biochemical and environmental/experiential factors. Careful diagnosis, using contemporary psychiatric criteria, simplifies treatment by the family physician. Awareness of these criteria may lead to improved selection of candidates for drug treatment and early intervention in recurrent illness. The new nosology in psychiatry avoids much confusion and should take some of the guesswork out of psychiatric treatment in the family physician's office.", "contents": "Depression: a new approach to an old syndrome. Depression is a medical illness related to an interplay of genetic, biochemical and environmental/experiential factors. Careful diagnosis, using contemporary psychiatric criteria, simplifies treatment by the family physician. Awareness of these criteria may lead to improved selection of candidates for drug treatment and early intervention in recurrent illness. The new nosology in psychiatry avoids much confusion and should take some of the guesswork out of psychiatric treatment in the family physician's office."}
{"id": "PMID:30273", "title": "Binding of bile acids by dietary fiber.", "content": "Binding of bile salts to food residue was studied in vitro and in vivo. In the in vitro experiments, residues of a number of foods were incubated with each of several bile salts at different concentrations and pHs. All food residues tested adsorbed more dihydroxy than trihydroxy bile salts. Bile salt binding increased as bile salt concentration increased and was greater at a low pH. The extent of bile salt adsorption to some food residues could be clinically important. In patients with short ileal resections, we compared the rates of fecal excretion of labelled cholic and chenodeoxycholic acids and of a nonabsorable marker during ingestion of an ordianry diet (approximately 5 g of fiber) and a residue-free liquid diet. Coefficients of bile salt adsorption were calculated. Both bile acids were absorbed more efficiently during the liquid diet. Chenodeoxycholic acid was preferentially bound to the particulate matter of stools of patients eating the fiber-containing diet. It seems possible that dietary fiber could affect the enterohepatic circulation of bile salts in certain patients with ileal resection.", "contents": "Binding of bile acids by dietary fiber. Binding of bile salts to food residue was studied in vitro and in vivo. In the in vitro experiments, residues of a number of foods were incubated with each of several bile salts at different concentrations and pHs. All food residues tested adsorbed more dihydroxy than trihydroxy bile salts. Bile salt binding increased as bile salt concentration increased and was greater at a low pH. The extent of bile salt adsorption to some food residues could be clinically important. In patients with short ileal resections, we compared the rates of fecal excretion of labelled cholic and chenodeoxycholic acids and of a nonabsorable marker during ingestion of an ordianry diet (approximately 5 g of fiber) and a residue-free liquid diet. Coefficients of bile salt adsorption were calculated. Both bile acids were absorbed more efficiently during the liquid diet. Chenodeoxycholic acid was preferentially bound to the particulate matter of stools of patients eating the fiber-containing diet. It seems possible that dietary fiber could affect the enterohepatic circulation of bile salts in certain patients with ileal resection."}
{"id": "PMID:30274", "title": "Accuracy and precision of urinary pH determinations using two commercially available dipsticks.", "content": "The accuracy and precision of urinary pH determinations using commercially available dipsticks were studied. Two products were evaluated by 17 MT(ASCP) technologists over the pH range 4.5 to 9.0. The study included accuracy, reproducibility, variation among technologists, and variation between products. The results demonstrated considerable variation among technologists, products, and true pH levels in dipstick urinary pH determinations, and that very good or very poor results could be obtained, depending on the true pH level being sampled and on the choice of technologist.", "contents": "Accuracy and precision of urinary pH determinations using two commercially available dipsticks. The accuracy and precision of urinary pH determinations using commercially available dipsticks were studied. Two products were evaluated by 17 MT(ASCP) technologists over the pH range 4.5 to 9.0. The study included accuracy, reproducibility, variation among technologists, and variation between products. The results demonstrated considerable variation among technologists, products, and true pH levels in dipstick urinary pH determinations, and that very good or very poor results could be obtained, depending on the true pH level being sampled and on the choice of technologist."}
{"id": "PMID:30276", "title": "Urinary nitrite and urinary-tract infection.", "content": "Two dipstick procedures and an automated quantitative urinary nitrite assay were used to study nitrite in 786 samples of urine submitted to the bacteriology laboratory for routine culture and sensitivity testing. Many samples that had more than 100,000 nitrite-reducing organisms/ml and no detectable nitrite were studied. Limited nitrate concentration in urine was not a significant cause of false-negative nitrite results. However, in some urine samples nitrite added in vitro was lost during a four-hour incubation in vitro at 37 C in the presence of more than 100,000 nitrite-reducing organisms/ml. Ascorbic acid, abnormal amounts of urobilinogen, and urinary pH below 6.0 are all possible causes of false-negative nitrite determinations.", "contents": "Urinary nitrite and urinary-tract infection. Two dipstick procedures and an automated quantitative urinary nitrite assay were used to study nitrite in 786 samples of urine submitted to the bacteriology laboratory for routine culture and sensitivity testing. Many samples that had more than 100,000 nitrite-reducing organisms/ml and no detectable nitrite were studied. Limited nitrate concentration in urine was not a significant cause of false-negative nitrite results. However, in some urine samples nitrite added in vitro was lost during a four-hour incubation in vitro at 37 C in the presence of more than 100,000 nitrite-reducing organisms/ml. Ascorbic acid, abnormal amounts of urobilinogen, and urinary pH below 6.0 are all possible causes of false-negative nitrite determinations."}
{"id": "PMID:30277", "title": "Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine.", "content": "Histamine H-2 receptors are thought to mediate gastric acid secretory responses, whereas H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 mumol/kg) into the stomach flap reduced histamine-stimulated (1.25 micron/kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 mumol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mumol/kg), whereas intravenously administered tripelennamine (40.8 mumol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methylhistamine (2.2 micron/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 micron/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists.", "contents": "Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine. Histamine H-2 receptors are thought to mediate gastric acid secretory responses, whereas H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 mumol/kg) into the stomach flap reduced histamine-stimulated (1.25 micron/kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 mumol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mumol/kg), whereas intravenously administered tripelennamine (40.8 mumol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methylhistamine (2.2 micron/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 micron/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists."}
{"id": "PMID:30279", "title": "Impairment of secretin release in celiac sprue.", "content": "Plasma secretin concentrations and pH in the second portion of duodenum were measured in the fasting state and during duodenal infusion of HCl in five patients with untreated celiac sprue, five celiac sprue patients after gluten-free diets, and five normal subjects. Mean fasting plasma secretin concentrations were insignificantly lower in untreated sprue patients (4.1 +/- 1.4 pg/ml) than in normal subjects (5.7 +/- 0.59 pg/ml). During 30-min intraduodenal infusions of 0.1 N HCl at 0.20 mEqH+/min, mean plasma secretin concentrations were significantly lower in untreated sprue patients (5.8 +/- 1.8 pg/ml) than in normal subjects (25.4 +/- 1.60 pg/ml, P less than 0.01). The increases in mean secretin concentrations over fasting were 2.1 +/- 0.82 pg/ml in untreated sprue patients compared to 19.7 +/- 1.47 pg/ml in normal subjects (P less than 0.01), a ninefold difference. The results indicate that endogenous release of secretin in response to duodenal acidification is impaired in patients with celiac sprue.", "contents": "Impairment of secretin release in celiac sprue. Plasma secretin concentrations and pH in the second portion of duodenum were measured in the fasting state and during duodenal infusion of HCl in five patients with untreated celiac sprue, five celiac sprue patients after gluten-free diets, and five normal subjects. Mean fasting plasma secretin concentrations were insignificantly lower in untreated sprue patients (4.1 +/- 1.4 pg/ml) than in normal subjects (5.7 +/- 0.59 pg/ml). During 30-min intraduodenal infusions of 0.1 N HCl at 0.20 mEqH+/min, mean plasma secretin concentrations were significantly lower in untreated sprue patients (5.8 +/- 1.8 pg/ml) than in normal subjects (25.4 +/- 1.60 pg/ml, P less than 0.01). The increases in mean secretin concentrations over fasting were 2.1 +/- 0.82 pg/ml in untreated sprue patients compared to 19.7 +/- 1.47 pg/ml in normal subjects (P less than 0.01), a ninefold difference. The results indicate that endogenous release of secretin in response to duodenal acidification is impaired in patients with celiac sprue."}
{"id": "PMID:30280", "title": "Rapid emesis from high-dose ipecac syrup in adults and children intoxicated with antiemetics or other drugs.", "content": "The effect of ipecac syrup as an emetic in adults as well as children who had ingested antiemetics or other drugs was evaluated. Adults or children over five years of age were given 30 ml of ipecac syrup followed by 360 ml of water; children aged one to five years were given 15 ml ipecac syrup followed by 240 ml of water. If emesis was not induced within 30 minutes, a second dose was administered. Of 232 patients studied (199 adults and 33 children), 188 (81%) vomited following the first dose, 34 (15%) required two doses and seven (3%) did not vomit. Of 63 patients who had ingested drugs with antiemetic properties, 51 (81%) vomited following the first dose, nine (14%) required a second dose and three (5%) did not vomit. The time from ipecac administration to the onset of emesis in all 232 patients averaged 24.2 minutes. Ipecac was successful in inducing rapid emesis in both adults and children who had ingested antiemetics or other drugs, probably as a result of its irritating effect on the gastric mucosa.", "contents": "Rapid emesis from high-dose ipecac syrup in adults and children intoxicated with antiemetics or other drugs. The effect of ipecac syrup as an emetic in adults as well as children who had ingested antiemetics or other drugs was evaluated. Adults or children over five years of age were given 30 ml of ipecac syrup followed by 360 ml of water; children aged one to five years were given 15 ml ipecac syrup followed by 240 ml of water. If emesis was not induced within 30 minutes, a second dose was administered. Of 232 patients studied (199 adults and 33 children), 188 (81%) vomited following the first dose, 34 (15%) required two doses and seven (3%) did not vomit. Of 63 patients who had ingested drugs with antiemetic properties, 51 (81%) vomited following the first dose, nine (14%) required a second dose and three (5%) did not vomit. The time from ipecac administration to the onset of emesis in all 232 patients averaged 24.2 minutes. Ipecac was successful in inducing rapid emesis in both adults and children who had ingested antiemetics or other drugs, probably as a result of its irritating effect on the gastric mucosa."}
{"id": "PMID:30282", "title": "Cardiac systolic time intervals in fetal monkeys: pre-ejection period.", "content": "The systolic time intervals of the fetal cardiac cycle were studied by means of simultaneous recordings of electrocardiogram (ECG) and ultrasound Doppler cardiogram (DCG) in chronic preparations of fetal rhesus monkeys. Recordings were made under physiologic conditions as well as during various experimental stresses. The pre-ejection period (PEP) showed no significant relationship with heart rate in the unstressed fetuses, but the acceleration of heart rate induced by epinephrine was accompanied by shortening of PEP. The PEP increased with advancing fetal age. The PEP was inversely correlated with left ventricular end-diastolic pressure and arterial pulse pressure, but showed a positive correlation with both systolic and diastolic arterial blood pressure. The PEP also exhibited strong negative correlation with arterial blood pH. the prolongation was essentially the same whether acidosis was of respiratory or metabolic origin. The PEP increased slightly but significantly during nonacidemic hypoxemia; however, there was no correlation between Pao2 and PEP Epinephrine shortened the PEP significantly, whereas the effect of atropine was inconsistent. Alteration of the plasma glucose level by injection of insulin or glucose did not affect PEP. These findings demonstrate that the PEP may be a useful indicator of fetal cardiac performance, reflecting both myocardial contractility and the hemodynamic state of the cardiovascular system.", "contents": "Cardiac systolic time intervals in fetal monkeys: pre-ejection period. The systolic time intervals of the fetal cardiac cycle were studied by means of simultaneous recordings of electrocardiogram (ECG) and ultrasound Doppler cardiogram (DCG) in chronic preparations of fetal rhesus monkeys. Recordings were made under physiologic conditions as well as during various experimental stresses. The pre-ejection period (PEP) showed no significant relationship with heart rate in the unstressed fetuses, but the acceleration of heart rate induced by epinephrine was accompanied by shortening of PEP. The PEP increased with advancing fetal age. The PEP was inversely correlated with left ventricular end-diastolic pressure and arterial pulse pressure, but showed a positive correlation with both systolic and diastolic arterial blood pressure. The PEP also exhibited strong negative correlation with arterial blood pH. the prolongation was essentially the same whether acidosis was of respiratory or metabolic origin. The PEP increased slightly but significantly during nonacidemic hypoxemia; however, there was no correlation between Pao2 and PEP Epinephrine shortened the PEP significantly, whereas the effect of atropine was inconsistent. Alteration of the plasma glucose level by injection of insulin or glucose did not affect PEP. These findings demonstrate that the PEP may be a useful indicator of fetal cardiac performance, reflecting both myocardial contractility and the hemodynamic state of the cardiovascular system."}
{"id": "PMID:30287", "title": "Withdrawal syndromes associated with antipsychotic drugs.", "content": "Withdrawal symptoms frequently follow abrupt discontinuation of antipsychotic compounds. In addition to other somatic symptoms, withdrawal-emergent dyskinesias may be observed. \"Covert dyskinesia\" refers to a masked form of tardive dyskinesia that becomes clinically detectable only after antipsychotic drugs are withdrawn or their dosage is reduced. Withdrawal dyskinesia appears under similar circumstances but disappears spontaneously in 6 to 12 weeks. Cholinergic overactivity and changes in dopamine-acetylcholine balance in the basal ganglia may underlie these withdrawal syndromes. The principal value of the concept of covert dyskinesia is in the secondary and tertiary prevention of tardive dyskinesia through early discovery and treatment.", "contents": "Withdrawal syndromes associated with antipsychotic drugs. Withdrawal symptoms frequently follow abrupt discontinuation of antipsychotic compounds. In addition to other somatic symptoms, withdrawal-emergent dyskinesias may be observed. \"Covert dyskinesia\" refers to a masked form of tardive dyskinesia that becomes clinically detectable only after antipsychotic drugs are withdrawn or their dosage is reduced. Withdrawal dyskinesia appears under similar circumstances but disappears spontaneously in 6 to 12 weeks. Cholinergic overactivity and changes in dopamine-acetylcholine balance in the basal ganglia may underlie these withdrawal syndromes. The principal value of the concept of covert dyskinesia is in the secondary and tertiary prevention of tardive dyskinesia through early discovery and treatment."}
{"id": "PMID:30288", "title": "The social context of schizophrenia.", "content": "During the past 25 years psychiatry has increased its understanding of the social context of schizophrenia in four major areas. Reasonable reliability can now be achieved in describing and recognizing many of the acute and chronic syndromes, so that comparability can be achieved between different research teams. Much is now known about the proximate social causes of symptoms and disabilities. The relationship between social and pharmacological treatments is now better understood. A more rational approach to the planning and prescription of services and to the counseling of patients and relatives can be made. Each of these lines of advance promises to lead to further progress in the future.", "contents": "The social context of schizophrenia. During the past 25 years psychiatry has increased its understanding of the social context of schizophrenia in four major areas. Reasonable reliability can now be achieved in describing and recognizing many of the acute and chronic syndromes, so that comparability can be achieved between different research teams. Much is now known about the proximate social causes of symptoms and disabilities. The relationship between social and pharmacological treatments is now better understood. A more rational approach to the planning and prescription of services and to the counseling of patients and relatives can be made. Each of these lines of advance promises to lead to further progress in the future."}
{"id": "PMID:30295", "title": "[Medical check-ups and selection of subjects: some results from a gerontological field-study (author's transl)].", "content": "In a gerontological field-study in Cologne, West-Germany, 1114 subjects of a random sample of elderlies were successively offered three modalities for a medical check-up, which covered a physical examination and a psychiatric interview: 1. in the out-patient department of a psychiatric hospital (Rheinische Landesklinik K\u00f6ln) (38% of the subjects); 2. in the subjects' home by a psychiatrist of the hospital (13%); 3. by having the general practitioner fill out a questionnaire (21%). There remained a fourth group of subjects who refused any medical check-up (28%). Data on social and economic problems had been obtained for all subjects in a preceding interview. These data were used to find out to what extent selection mechanisms were effective. Results indicate that to a certain extent the modality of the medical check-up chosen by the subject is related to some of the variables analyzed.", "contents": "[Medical check-ups and selection of subjects: some results from a gerontological field-study (author's transl)]. In a gerontological field-study in Cologne, West-Germany, 1114 subjects of a random sample of elderlies were successively offered three modalities for a medical check-up, which covered a physical examination and a psychiatric interview: 1. in the out-patient department of a psychiatric hospital (Rheinische Landesklinik K\u00f6ln) (38% of the subjects); 2. in the subjects' home by a psychiatrist of the hospital (13%); 3. by having the general practitioner fill out a questionnaire (21%). There remained a fourth group of subjects who refused any medical check-up (28%). Data on social and economic problems had been obtained for all subjects in a preceding interview. These data were used to find out to what extent selection mechanisms were effective. Results indicate that to a certain extent the modality of the medical check-up chosen by the subject is related to some of the variables analyzed."}
{"id": "PMID:30296", "title": "[Collecting data on the state of health of the elderly by mail survey of family doctors (author's transl)].", "content": "In connection with a gerontological research project data on the physical of the persons being investigated were, amongst other sources, also obtained through a mail survey of family doctors. How far survey shortcomings have a distorting effect was studied. The results indicate that a mail survey of family doctors may yield appropriate data even if some of the physicians named by the persons being investigated do not respond.", "contents": "[Collecting data on the state of health of the elderly by mail survey of family doctors (author's transl)]. In connection with a gerontological research project data on the physical of the persons being investigated were, amongst other sources, also obtained through a mail survey of family doctors. How far survey shortcomings have a distorting effect was studied. The results indicate that a mail survey of family doctors may yield appropriate data even if some of the physicians named by the persons being investigated do not respond."}
{"id": "PMID:30297", "title": "[Study on the effectiveness of the \"Berlin Letters for Seniors (author's transl)].", "content": "The effectiveness of the \"Berlin Letters for Seniors\" (LFS) will be tested by a longitudinal study. Two Measurement Points (MP) are scheduled: 1976 and 1978. The total sample (N = 3000) comprehends two subsamples of receivers and non-receivers. Data were/will be collected by a questionnaire. A preliminary analysis of the MP I data shows that the two subsamples are comparable as to demographic variables and relevant attitudes; so they may serve as experimental versus control group. An examination of what the readers' concept of the LFS was like, proved that though reservation was recognizable approval prevails.", "contents": "[Study on the effectiveness of the \"Berlin Letters for Seniors (author's transl)]. The effectiveness of the \"Berlin Letters for Seniors\" (LFS) will be tested by a longitudinal study. Two Measurement Points (MP) are scheduled: 1976 and 1978. The total sample (N = 3000) comprehends two subsamples of receivers and non-receivers. Data were/will be collected by a questionnaire. A preliminary analysis of the MP I data shows that the two subsamples are comparable as to demographic variables and relevant attitudes; so they may serve as experimental versus control group. An examination of what the readers' concept of the LFS was like, proved that though reservation was recognizable approval prevails."}
{"id": "PMID:30298", "title": "[Stress of the elderly (author's transl)].", "content": "Author examines the suicide-motives of elderly people in connection with stress and describes the Hedri-Mallisons disease, which has a very high suicide-rate.", "contents": "[Stress of the elderly (author's transl)]. Author examines the suicide-motives of elderly people in connection with stress and describes the Hedri-Mallisons disease, which has a very high suicide-rate."}
{"id": "PMID:30324", "title": "[Survived brain infarction in old age - clinical and morphological findings. II. Risk factors (author's transl)].", "content": "208 hospitalized patients, nearly 80 years old, were investigated because of risk factors and complicating diseases. Hypertension (58.2%), typical myocardial infarctions (37.2%) and diabetes (45.2%) were twice often as in our comparable cases without stroke. Corresponding we found signs of left ventricular hypertrophy in more than 50% post mortem. The dimensions of heart failure by hypertension are visible in ECG indicating LVH with many dysrhythmias. Early mortality (40%) as survival time are dependent on the size of the stroke. Cardiovascular causes of death were found mainly. The differences to younger patients with brain infarction seem to be only of gradually nature and especially to refer to the more intensive damaged heart.", "contents": "[Survived brain infarction in old age - clinical and morphological findings. II. Risk factors (author's transl)]. 208 hospitalized patients, nearly 80 years old, were investigated because of risk factors and complicating diseases. Hypertension (58.2%), typical myocardial infarctions (37.2%) and diabetes (45.2%) were twice often as in our comparable cases without stroke. Corresponding we found signs of left ventricular hypertrophy in more than 50% post mortem. The dimensions of heart failure by hypertension are visible in ECG indicating LVH with many dysrhythmias. Early mortality (40%) as survival time are dependent on the size of the stroke. Cardiovascular causes of death were found mainly. The differences to younger patients with brain infarction seem to be only of gradually nature and especially to refer to the more intensive damaged heart."}
{"id": "PMID:30325", "title": "[Prosthetic fitting in the geriatric leg amputee (author's transl)].", "content": "This retrospective study regarding prosthetic fitting in geriatric amputees showed that only about 50 per cent of the patients could be fitted with a prosthesis. The time interval from the amputation until the patients walked adequately with the prostheses was very long. This was due to problems with the healing of the stump, as well as insufficiencies in the medical organization. An increased coordination of the care of these patients before and after an amputation would improve the whole course of events. It is suggested that the main responsibility for these patients should be transferred to physicians, specialized in long-term care medicine.", "contents": "[Prosthetic fitting in the geriatric leg amputee (author's transl)]. This retrospective study regarding prosthetic fitting in geriatric amputees showed that only about 50 per cent of the patients could be fitted with a prosthesis. The time interval from the amputation until the patients walked adequately with the prostheses was very long. This was due to problems with the healing of the stump, as well as insufficiencies in the medical organization. An increased coordination of the care of these patients before and after an amputation would improve the whole course of events. It is suggested that the main responsibility for these patients should be transferred to physicians, specialized in long-term care medicine."}
{"id": "PMID:30326", "title": "[Application of laser rays in surgery (author's transl)].", "content": "Some years will have to pass, until there will be evidence, if application of leaser beam in surgery of Breastcancer, Melanomas or Basaliomas was justified and whether it is possible or not to interrupt or reduce intraoperative tumor cellspread. As an increasing number of surgeons have started to use laser rays in these illnesses, result of laser surgery and those of traditional methods could be compared in a couple of years. Possibly other indications will be outlined in general surgery for the use of laser beside those we have been working out. It may happen that surgeons working with laser beam might bring the method into discredit putting indication not rigorous enough. I should like to remind everybody who starts working with laser rays, to do so with greatest possible care. Collaboration with a technician is recommended. Periodic he should control the machine and handle arising technical problems.", "contents": "[Application of laser rays in surgery (author's transl)]. Some years will have to pass, until there will be evidence, if application of leaser beam in surgery of Breastcancer, Melanomas or Basaliomas was justified and whether it is possible or not to interrupt or reduce intraoperative tumor cellspread. As an increasing number of surgeons have started to use laser rays in these illnesses, result of laser surgery and those of traditional methods could be compared in a couple of years. Possibly other indications will be outlined in general surgery for the use of laser beside those we have been working out. It may happen that surgeons working with laser beam might bring the method into discredit putting indication not rigorous enough. I should like to remind everybody who starts working with laser rays, to do so with greatest possible care. Collaboration with a technician is recommended. Periodic he should control the machine and handle arising technical problems."}
{"id": "PMID:30327", "title": "[The cardiotropic effect of antidepressants in aging patients (author's transl)].", "content": "All antidepressants now used have a cardiotropic, for some instances also cardiotoxic effect. This quinidine-like effect prolongs the QT-interval of ECG and can induce reentry and ventricular fibrillation. When quinidine and antidepressants are combined in the same patient the risk of such cardiac complications increases.", "contents": "[The cardiotropic effect of antidepressants in aging patients (author's transl)]. All antidepressants now used have a cardiotropic, for some instances also cardiotoxic effect. This quinidine-like effect prolongs the QT-interval of ECG and can induce reentry and ventricular fibrillation. When quinidine and antidepressants are combined in the same patient the risk of such cardiac complications increases."}
{"id": "PMID:30328", "title": "[Autoimmune phenomena in the aging, cerebral atherosclerosis, Parkinsonism (author's transl)].", "content": "Studies were undertaken on the immune reactions in aging at cerebral atherosclerosis and parkinsonism. With age a number of changes occurred, which were characterized by a decrease in specific and non-specific immunity, against the background of which the autoimmune reactions were developing. There was an increase in the frequency of the detection of antibodies to antigens of the brain as well as in those of the aorta, heart, liver and pancreatic gland. The \"peak\" of autoimmune reactions was registered at 65 years in men and 75 years in women. There were lymphocytes in the peripheral blood, which together with homologic antigens inhibited the migration of macrophages. In subjects aged 90 years and over the autoantibodies occurred in a lower percent of cases as compared with the subjects aged 60--74. In subjects aged 45--55 with cerebral atherosclerosis the indices under study appeared to be close to those in healthy persons aged 60--74. Still more marked immunological shifts were found in patients with parkinsonism. The findings may suggest a certain role of the autoimmune mechanisms in pathogenesis of some forms of nervous pathology at late stages of ontogenesis and atherosclerosis.", "contents": "[Autoimmune phenomena in the aging, cerebral atherosclerosis, Parkinsonism (author's transl)]. Studies were undertaken on the immune reactions in aging at cerebral atherosclerosis and parkinsonism. With age a number of changes occurred, which were characterized by a decrease in specific and non-specific immunity, against the background of which the autoimmune reactions were developing. There was an increase in the frequency of the detection of antibodies to antigens of the brain as well as in those of the aorta, heart, liver and pancreatic gland. The \"peak\" of autoimmune reactions was registered at 65 years in men and 75 years in women. There were lymphocytes in the peripheral blood, which together with homologic antigens inhibited the migration of macrophages. In subjects aged 90 years and over the autoantibodies occurred in a lower percent of cases as compared with the subjects aged 60--74. In subjects aged 45--55 with cerebral atherosclerosis the indices under study appeared to be close to those in healthy persons aged 60--74. Still more marked immunological shifts were found in patients with parkinsonism. The findings may suggest a certain role of the autoimmune mechanisms in pathogenesis of some forms of nervous pathology at late stages of ontogenesis and atherosclerosis."}
{"id": "PMID:30329", "title": "[A meaningful antibiotic therapy of diseases of the ear, nose and throat in old age (author's transl)].", "content": "Each stage of life is characterized by the prevalence of certain affections; among others, inflammatory diseases of the ear, nose and throat are frequent in old age. Therefore, specific problems of chemotherapy in old age are dealt with in general terms in the introduction, with special stress being placed on the functions of individual organs, mainly of the kidneys, and on questions of disturbed absorption. Inflammations caused by streptococci, requiring at least ten days of antibiotic treatment, always deserve particular attention, and so do staphyloccocal diseases, requiring the selective administration of semi-synthetic pencillines (sioxazol preparations). Penicillin is still the first choice among all antibiotics, penicillin substitutes, to be used in case of allergies, are listed according to their order of value. As anaerobic germs may also be present in the ENT area, the effective modern therapy by means of special antibiotics is also referred to. Finally, due consideration is given to local antibiotic therapy, with an emphasis on the ototoxicity of chemotherapeutical agents, such as amino-glycosides.", "contents": "[A meaningful antibiotic therapy of diseases of the ear, nose and throat in old age (author's transl)]. Each stage of life is characterized by the prevalence of certain affections; among others, inflammatory diseases of the ear, nose and throat are frequent in old age. Therefore, specific problems of chemotherapy in old age are dealt with in general terms in the introduction, with special stress being placed on the functions of individual organs, mainly of the kidneys, and on questions of disturbed absorption. Inflammations caused by streptococci, requiring at least ten days of antibiotic treatment, always deserve particular attention, and so do staphyloccocal diseases, requiring the selective administration of semi-synthetic pencillines (sioxazol preparations). Penicillin is still the first choice among all antibiotics, penicillin substitutes, to be used in case of allergies, are listed according to their order of value. As anaerobic germs may also be present in the ENT area, the effective modern therapy by means of special antibiotics is also referred to. Finally, due consideration is given to local antibiotic therapy, with an emphasis on the ototoxicity of chemotherapeutical agents, such as amino-glycosides."}
{"id": "PMID:30330", "title": "[Stereological investigation in the cerebral cortex of aging subjects (author's transl)].", "content": "Involving cortical regions, capillaries of the human cerebrum of two 19 and 27 years old men, a 69 years old woman and a 72 years old man were stereologically investigated by optical-electronic image-analysis. The cortical capillary net work was demonstrated by the alkaline phosphatase activity. Each cortex region comprised a determination of the stereological parameters diameter, projected area, specific surface area, capillary distances in linear direction of TV-lines and total length per unit cortex volume. A comparison between different cortex regions revealed a good correlation between increased values of the diameter and the projected area, a decreased specific surface area and diminished capillary distances, which entail a shortened distance of oxygen diffusion through the cortical tissue. During aging a diminished capillary surface area, which results from increased values of diameter and projected area is compensated by shortened capillary distances. Presumably an augmented capillary length is due to a condensation of the capillary net per unit cortex tissue. The behaviour of the registered stereological parameters seems to be an accommodation of the capillary net in the human cerebrum to metabolic and circulatory changes during aging.", "contents": "[Stereological investigation in the cerebral cortex of aging subjects (author's transl)]. Involving cortical regions, capillaries of the human cerebrum of two 19 and 27 years old men, a 69 years old woman and a 72 years old man were stereologically investigated by optical-electronic image-analysis. The cortical capillary net work was demonstrated by the alkaline phosphatase activity. Each cortex region comprised a determination of the stereological parameters diameter, projected area, specific surface area, capillary distances in linear direction of TV-lines and total length per unit cortex volume. A comparison between different cortex regions revealed a good correlation between increased values of the diameter and the projected area, a decreased specific surface area and diminished capillary distances, which entail a shortened distance of oxygen diffusion through the cortical tissue. During aging a diminished capillary surface area, which results from increased values of diameter and projected area is compensated by shortened capillary distances. Presumably an augmented capillary length is due to a condensation of the capillary net per unit cortex tissue. The behaviour of the registered stereological parameters seems to be an accommodation of the capillary net in the human cerebrum to metabolic and circulatory changes during aging."}
{"id": "PMID:30331", "title": "Leucocyte migration test and hypersensitivity to glafenin.", "content": "The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.", "contents": "Leucocyte migration test and hypersensitivity to glafenin. The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin."}
{"id": "PMID:30340", "title": "Increasing halothane concentrations reduce nitroprusside dose requirement.", "content": "There has been no description of the hemodynamic dose-response relationship between halothane and sodium nitroprusside (SNP), although these drugs are used together frequently for induction of deliberate hypotension. Utilizing aortic root cannulation and thermister-tipped pulmonary artery catheterization, this relationship was studied in 6 beagles receiving a standard 100 microgram/kg infusion of SNP solution administered at 3 different infusion rates (5, 10, and 20 microgram/kg/min) while anesthetized with 3 different concentrations of halothane (0.5, 1, and 2%). Sodium nitroprusside infusion resulted in dose-related reductions in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work. Increasing concentrations of halothane significantly potentiated the hypotensive effects of SNP. Cardiac output increase as the SNP infusion rate increased, whereas increasing the halothane concentration resulted in a reduction of cardiac output at each SNP infusion rate studied. Pulmonary artery wedge pressure was significantly reduced by SNP infusion at all 3 halothane concentrations, whereas mean pulmonary artery pressure was unchanged. Arterial pH fell in response to each SNP infusion, from 7.46 at the beginning of the study to 7.32 at the end (p less than 0.001). Sodium nitroprusside predictably induced hypotension during halothane anesthesia at the cost of a dose-related metabolic acidosis. Increasing the depth of halothane anesthesia afforded a greater percentage reduction in arterial pressure at each SNP infusion rate studied. Metabolic acidosis, however, developed no more rapidly at 2% halothane than it did at 0.5 or 1%.", "contents": "Increasing halothane concentrations reduce nitroprusside dose requirement. There has been no description of the hemodynamic dose-response relationship between halothane and sodium nitroprusside (SNP), although these drugs are used together frequently for induction of deliberate hypotension. Utilizing aortic root cannulation and thermister-tipped pulmonary artery catheterization, this relationship was studied in 6 beagles receiving a standard 100 microgram/kg infusion of SNP solution administered at 3 different infusion rates (5, 10, and 20 microgram/kg/min) while anesthetized with 3 different concentrations of halothane (0.5, 1, and 2%). Sodium nitroprusside infusion resulted in dose-related reductions in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work. Increasing concentrations of halothane significantly potentiated the hypotensive effects of SNP. Cardiac output increase as the SNP infusion rate increased, whereas increasing the halothane concentration resulted in a reduction of cardiac output at each SNP infusion rate studied. Pulmonary artery wedge pressure was significantly reduced by SNP infusion at all 3 halothane concentrations, whereas mean pulmonary artery pressure was unchanged. Arterial pH fell in response to each SNP infusion, from 7.46 at the beginning of the study to 7.32 at the end (p less than 0.001). Sodium nitroprusside predictably induced hypotension during halothane anesthesia at the cost of a dose-related metabolic acidosis. Increasing the depth of halothane anesthesia afforded a greater percentage reduction in arterial pressure at each SNP infusion rate studied. Metabolic acidosis, however, developed no more rapidly at 2% halothane than it did at 0.5 or 1%."}
{"id": "PMID:30341", "title": "Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R): an experimental study.", "content": "We describe a new form of mechanical pulmonary ventilation, low-frequency positive pressure ventilation with extracorporeal CO2 removal (LEPPV-ECCO2R). In a series of animal studies the rate of mechanical ventilation was 0.66, 1, 2, and 4 min-1 at a tidal volume of 3, 10, and 15 ml kg-1. We were able to maintain normal blood gases and normal lung volumes and lung mechanics even at the lowest ventilator rate with tidal volumes of 10 or 15 ml kg-1. Each experiment lasted 7 hours. Our data suggest a possible new dimension in the management of a difficult patient on mechanical pulmonary ventilation.", "contents": "Low-frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R): an experimental study. We describe a new form of mechanical pulmonary ventilation, low-frequency positive pressure ventilation with extracorporeal CO2 removal (LEPPV-ECCO2R). In a series of animal studies the rate of mechanical ventilation was 0.66, 1, 2, and 4 min-1 at a tidal volume of 3, 10, and 15 ml kg-1. We were able to maintain normal blood gases and normal lung volumes and lung mechanics even at the lowest ventilator rate with tidal volumes of 10 or 15 ml kg-1. Each experiment lasted 7 hours. Our data suggest a possible new dimension in the management of a difficult patient on mechanical pulmonary ventilation."}
{"id": "PMID:30347", "title": "[Perforations of the dura mater during epidural anesthesia. The value of epidurography].", "content": "The authors propose a pathogenic classification of perforations of the dura mater occurring during continuous epidural anaesthesia: according to the flow through the communication with the subarochnoid space. Two clinical forms of anaesthesia affecting the cord itself may be distinguished on this basis, one frequent and of immediate onset, diagnosed by the \"test dose\" and the other rare, of delayed onset, where this safety measure does not suffice. Routine prior epidurography is suggested, in order to ensure the diagnosis of dura mater perforation. In the case of the latter, it show either a more or less typical appearance of radicolography only or, more rarely, a picture which combines opacification of the epidural space with the subarachnoid passage of the contrast medium. This \"mixed\" appearance, although rare, should be known since it makes it possible to prevent delayed total spinal anaesthesia.", "contents": "[Perforations of the dura mater during epidural anesthesia. The value of epidurography]. The authors propose a pathogenic classification of perforations of the dura mater occurring during continuous epidural anaesthesia: according to the flow through the communication with the subarochnoid space. Two clinical forms of anaesthesia affecting the cord itself may be distinguished on this basis, one frequent and of immediate onset, diagnosed by the \"test dose\" and the other rare, of delayed onset, where this safety measure does not suffice. Routine prior epidurography is suggested, in order to ensure the diagnosis of dura mater perforation. In the case of the latter, it show either a more or less typical appearance of radicolography only or, more rarely, a picture which combines opacification of the epidural space with the subarachnoid passage of the contrast medium. This \"mixed\" appearance, although rare, should be known since it makes it possible to prevent delayed total spinal anaesthesia."}
{"id": "PMID:30342", "title": "Effects of pH on protein binding of lidocaine.", "content": "Protein binding of lidocaine (2.5, 5, 10, and 20 microgram/ml in fresh plasma was studied from pH 5.6 to pH 9.8. Percent binding of lidocaine was inversely related to hydrogen-ion and lidocaine concentrations.", "contents": "Effects of pH on protein binding of lidocaine. Protein binding of lidocaine (2.5, 5, 10, and 20 microgram/ml in fresh plasma was studied from pH 5.6 to pH 9.8. Percent binding of lidocaine was inversely related to hydrogen-ion and lidocaine concentrations."}
{"id": "PMID:30349", "title": "[Psychiatric complications in patients under intensive care].", "content": "Ten adult patients with psychiatric disorders in the intensive care ward were examined. The length of stay varied from one week to four months and mechanical ventilation was necessary for all patients. Their experience of intensive care and their psychosensorial problems were as follows: temperospatial disorientation, perturbation of the sense of posture, hallucinations which could go as far as oneiric delirium, anguish and symptoms of depression. No psychotic syndrome, literraly speaking, was observed objectively. In the monthes that followed the stay under intensive care many patients presented important psychosomatic disorders. Organic factors are responsible for these complications, though the environment of the intensive care could induce a marked disafferentation. An effort by the attending staff, aimed at orientating or \"reafferenting\" these patients, could reduce these problems.", "contents": "[Psychiatric complications in patients under intensive care]. Ten adult patients with psychiatric disorders in the intensive care ward were examined. The length of stay varied from one week to four months and mechanical ventilation was necessary for all patients. Their experience of intensive care and their psychosensorial problems were as follows: temperospatial disorientation, perturbation of the sense of posture, hallucinations which could go as far as oneiric delirium, anguish and symptoms of depression. No psychotic syndrome, literraly speaking, was observed objectively. In the monthes that followed the stay under intensive care many patients presented important psychosomatic disorders. Organic factors are responsible for these complications, though the environment of the intensive care could induce a marked disafferentation. An effort by the attending staff, aimed at orientating or \"reafferenting\" these patients, could reduce these problems."}
{"id": "PMID:30350", "title": "[Parenteral nutrition and concentrated amino acid solution].", "content": "The authors report on their experience with a solution of amino acids concentrated at 25 gomegaN/liter in eighty patients on exclusive and total parenteral nutrition (TPN). The average duration of the TPN is 35.08 days. Azonutril 25 was given as nutritive melange, maintaining a calorie-nitrogen ratio of 150 to 200 calories for every added gram of nitrogen. The clinical and biological studies provide a series of arguments in favor of such an amino acid solution in total parental nutrition in patients with acute or chronic digestive insufficiency. No signs of renal or hepatic intolerance have appeared during this study. The improvement in nitrogen balance in fifteen patients is strongly significant (P less than 0.001) and can be correlated with weight gain and with the classic immunological tests.", "contents": "[Parenteral nutrition and concentrated amino acid solution]. The authors report on their experience with a solution of amino acids concentrated at 25 gomegaN/liter in eighty patients on exclusive and total parenteral nutrition (TPN). The average duration of the TPN is 35.08 days. Azonutril 25 was given as nutritive melange, maintaining a calorie-nitrogen ratio of 150 to 200 calories for every added gram of nitrogen. The clinical and biological studies provide a series of arguments in favor of such an amino acid solution in total parental nutrition in patients with acute or chronic digestive insufficiency. No signs of renal or hepatic intolerance have appeared during this study. The improvement in nitrogen balance in fifteen patients is strongly significant (P less than 0.001) and can be correlated with weight gain and with the classic immunological tests."}
{"id": "PMID:30351", "title": "[Four cases of tracheoesophageal fistula associated with prolonged ventilation].", "content": "On the basis of four cases of oesophago-tracheal fistulae developing in ventilated patients, the authors describe the pathogenesis of these lesions, related to circulatory disturbances in the tracheal mucosa in contact with the balloon of the balloon of the tracheal tube. The spontaneous course is rapidly fatal and the results of surgical treatment remain disappointing. Prevention of these lesions is essential but difficult. It is based above all on the use of \"large volume and low pressure\" balloons, with periodic exsufflation. The diagnosis of these lesions must be make early and is base upon the development of tracheal dilatation, even minimal and seen radiologically by the appearance of the tube balloon. Such a finding should lead to endoscopic exploration of the tranchea and oesophagus, in order that treatment may be strated rapidly.", "contents": "[Four cases of tracheoesophageal fistula associated with prolonged ventilation]. On the basis of four cases of oesophago-tracheal fistulae developing in ventilated patients, the authors describe the pathogenesis of these lesions, related to circulatory disturbances in the tracheal mucosa in contact with the balloon of the balloon of the tracheal tube. The spontaneous course is rapidly fatal and the results of surgical treatment remain disappointing. Prevention of these lesions is essential but difficult. It is based above all on the use of \"large volume and low pressure\" balloons, with periodic exsufflation. The diagnosis of these lesions must be make early and is base upon the development of tracheal dilatation, even minimal and seen radiologically by the appearance of the tube balloon. Such a finding should lead to endoscopic exploration of the tranchea and oesophagus, in order that treatment may be strated rapidly."}
{"id": "PMID:30354", "title": "[Visual identification of Doppler sounds in gas embolisms].", "content": "The method of choice for the early detection of air metabolism during neurosurgical operations in a sitting position is that of continuous cardiac auscultation using Doppler effect ultrasound apparatus. In the present study, involving 15 patients, an air embolism was produced by the injection of 2 ml of CO2 into the right heart and acoustic changes were recorded on paper using a photographic process. These optical changes, although variable, were invariably present and characteristic of aire emboli and represent an additional element in early diagnosis.", "contents": "[Visual identification of Doppler sounds in gas embolisms]. The method of choice for the early detection of air metabolism during neurosurgical operations in a sitting position is that of continuous cardiac auscultation using Doppler effect ultrasound apparatus. In the present study, involving 15 patients, an air embolism was produced by the injection of 2 ml of CO2 into the right heart and acoustic changes were recorded on paper using a photographic process. These optical changes, although variable, were invariably present and characteristic of aire emboli and represent an additional element in early diagnosis."}
{"id": "PMID:30355", "title": "[Traumatic intoxication by an anticholinesterase agent].", "content": "An unusual observation is reported concerning intoxication by an anticholinesterasic. In this case a traumatic blow was caused by an industrial liquid projected under high pressure and resulted in a true parenteral injection. This product, presumed not to be toxic, lead to the delayed appearance of a massive and eventually fatal intoxication. The problemes of prevention, diagnosis and treatment of this type of intoxication are commented on.", "contents": "[Traumatic intoxication by an anticholinesterase agent]. An unusual observation is reported concerning intoxication by an anticholinesterasic. In this case a traumatic blow was caused by an industrial liquid projected under high pressure and resulted in a true parenteral injection. This product, presumed not to be toxic, lead to the delayed appearance of a massive and eventually fatal intoxication. The problemes of prevention, diagnosis and treatment of this type of intoxication are commented on."}
{"id": "PMID:30356", "title": "[Anesthetic evidence of pheochromocytoma].", "content": "The authors report the clinical case of a patients who underwent four anaesthetic inductions during a period of 3 months. Two were associated with severe acute hypertension making the intended operation impossible at that time. Thorough investigations led to a diagnosis of phaeochromocytoma. Reviewing the protocol of the four anaesthetic inductions, the authors discuss the mechanism of provocation of paroxysmal hypertension which was seen on two occasions.", "contents": "[Anesthetic evidence of pheochromocytoma]. The authors report the clinical case of a patients who underwent four anaesthetic inductions during a period of 3 months. Two were associated with severe acute hypertension making the intended operation impossible at that time. Thorough investigations led to a diagnosis of phaeochromocytoma. Reviewing the protocol of the four anaesthetic inductions, the authors discuss the mechanism of provocation of paroxysmal hypertension which was seen on two occasions."}
{"id": "PMID:30379", "title": "Calcium ion regulation in barnacle muscle fibers and its relation to force development.", "content": "It is possible to use the photoproteins aequorin and obelin within the slowly responding striated muscle films to provide both qualitative and quantitive information as to the nature of the calcium-dependent reactions for force development. It seems that these reactions are not in equilibrium with the Ca2+ during a transient response. In addition, these experiments suggest that kinetically at least two calciums are required per functional unit for force development and that this active site is competed for by Mg2+, H+, and K+ ions.", "contents": "Calcium ion regulation in barnacle muscle fibers and its relation to force development. It is possible to use the photoproteins aequorin and obelin within the slowly responding striated muscle films to provide both qualitative and quantitive information as to the nature of the calcium-dependent reactions for force development. It seems that these reactions are not in equilibrium with the Ca2+ during a transient response. In addition, these experiments suggest that kinetically at least two calciums are required per functional unit for force development and that this active site is competed for by Mg2+, H+, and K+ ions."}
{"id": "PMID:30380", "title": "Intracellular and extracellular calcium ions in transmitter release at the neuromuscular synapse.", "content": "The theme of this presentation has been to show that the control of transmitter release at the neuromuscular synapse is achieved by extracellular and intracellular calcium. For the fast information transfer represented by the end-plate potential, the electrochemical gradient for calcium across the presynaptic membrane and the associated calcium conductance seem to play the primary role. For slower processes such as tetanic and posttetanic potentiation, the combined effect of both sources for calcium determine the amount of transmitter liberated.", "contents": "Intracellular and extracellular calcium ions in transmitter release at the neuromuscular synapse. The theme of this presentation has been to show that the control of transmitter release at the neuromuscular synapse is achieved by extracellular and intracellular calcium. For the fast information transfer represented by the end-plate potential, the electrochemical gradient for calcium across the presynaptic membrane and the associated calcium conductance seem to play the primary role. For slower processes such as tetanic and posttetanic potentiation, the combined effect of both sources for calcium determine the amount of transmitter liberated."}
{"id": "PMID:30384", "title": "[Cutaneous periarteritis nodosa. Critical study about 4 cases (author's transl)].", "content": "Cutaneous form of periarteritis nodosa. Four personal cases are added to 70 cases of the previous literature. The clinical and biological picture of the cutaneous form of P.A.N. are different from the systemic one by the lack of visceral involvement and a noteworthy good long-term prognosis. Venous (superficial thrombophlebitis) and distal arterial involvement in some cases, raise doubts about diagnosis and classification. The solution is in an accurate definition of the diagnostic clues and specially of the histopathological ones.", "contents": "[Cutaneous periarteritis nodosa. Critical study about 4 cases (author's transl)]. Cutaneous form of periarteritis nodosa. Four personal cases are added to 70 cases of the previous literature. The clinical and biological picture of the cutaneous form of P.A.N. are different from the systemic one by the lack of visceral involvement and a noteworthy good long-term prognosis. Venous (superficial thrombophlebitis) and distal arterial involvement in some cases, raise doubts about diagnosis and classification. The solution is in an accurate definition of the diagnostic clues and specially of the histopathological ones."}
{"id": "PMID:30387", "title": "The graft-versus-host reaction in chickens: determination of some parameters.", "content": "Some aspects of the \"\"Graft-Versus-Host'' (GVH) reaction were studied in White Leghorn chickens by assessing the splenic response of recipients to an injection of lymphocytes from donors. The responses varied according to the origin of recipient embryos as well as to the source of the donor lymphocytes. Blood lymphocytes induced a higher splenomegaly in recipients than spleen lymphocytes, at least in the first seven weeks of life. The influence of the thymus on GVH reactions was also investigated. Lymphocytes from thymectomized chickens induced stronger responses than lymphocytes from non-thymectomized ones. These results support the conclusion that in the chicken T-lymphocytes may not be the only cells involved in the development of GVH reactions and cast some doubts on the reliability of GVH reactions to check the T specificity of immunological cellular responses.", "contents": "The graft-versus-host reaction in chickens: determination of some parameters. Some aspects of the \"\"Graft-Versus-Host'' (GVH) reaction were studied in White Leghorn chickens by assessing the splenic response of recipients to an injection of lymphocytes from donors. The responses varied according to the origin of recipient embryos as well as to the source of the donor lymphocytes. Blood lymphocytes induced a higher splenomegaly in recipients than spleen lymphocytes, at least in the first seven weeks of life. The influence of the thymus on GVH reactions was also investigated. Lymphocytes from thymectomized chickens induced stronger responses than lymphocytes from non-thymectomized ones. These results support the conclusion that in the chicken T-lymphocytes may not be the only cells involved in the development of GVH reactions and cast some doubts on the reliability of GVH reactions to check the T specificity of immunological cellular responses."}
{"id": "PMID:30388", "title": "A comparative study of three beta 1-adrenoreceptor blocking drugs with different degree of intrinsic stimulating activity (metoprolol, practolol and H 87/07) in patients with angina pectoris.", "content": "Three beta1-selective beta-blocker (metoprolol, practolol and H 87/07) were compared in 29 patients with stable angina pectoris. The main pharmacological difference between the three beta-blockers was their intrinsic stimulating activity (I.S.A.), metoprolol being devoid of I.S.A., practolol having moderate I.S.A. and H 87/07 having high I.S.A. Each drug was given in randomized order and the length of each cross-over period was 2 weeks. Daily activity was measured by an automatic step-counter, and subjective symptoms and nitroglycerin consumption were registered on a diary-card. Objective data, such as ECG changes and exercise capacity, were obtained by bicycle ergometer tests performed at the end of each period. At rest, the heart rate was significantly lower on metoprolol than on practolol or H 87/07. During exercise, the heart rate was significantly higher on H 87/07 than on practolol or metoprolol. No other haemodynamic differences were found between the three beta-blockers. No differences were found between the three test periods with regard to daily activity, expressed as the number of steps walked, while on the beta-blocker with high I.S.A., H 87/07, the attack rate and nitroglycerin consumption were significantly higher than when the patients were on metoprolol and practolol. No difference was found between the three beta-blockers with regard to total work or exercise time until 1 mm of S-T segment depression. Except for one patient who experienced a severe exanthema on practolol, the three beta-blockers were equally well tolerated.", "contents": "A comparative study of three beta 1-adrenoreceptor blocking drugs with different degree of intrinsic stimulating activity (metoprolol, practolol and H 87/07) in patients with angina pectoris. Three beta1-selective beta-blocker (metoprolol, practolol and H 87/07) were compared in 29 patients with stable angina pectoris. The main pharmacological difference between the three beta-blockers was their intrinsic stimulating activity (I.S.A.), metoprolol being devoid of I.S.A., practolol having moderate I.S.A. and H 87/07 having high I.S.A. Each drug was given in randomized order and the length of each cross-over period was 2 weeks. Daily activity was measured by an automatic step-counter, and subjective symptoms and nitroglycerin consumption were registered on a diary-card. Objective data, such as ECG changes and exercise capacity, were obtained by bicycle ergometer tests performed at the end of each period. At rest, the heart rate was significantly lower on metoprolol than on practolol or H 87/07. During exercise, the heart rate was significantly higher on H 87/07 than on practolol or metoprolol. No other haemodynamic differences were found between the three beta-blockers. No differences were found between the three test periods with regard to daily activity, expressed as the number of steps walked, while on the beta-blocker with high I.S.A., H 87/07, the attack rate and nitroglycerin consumption were significantly higher than when the patients were on metoprolol and practolol. No difference was found between the three beta-blockers with regard to total work or exercise time until 1 mm of S-T segment depression. Except for one patient who experienced a severe exanthema on practolol, the three beta-blockers were equally well tolerated."}
{"id": "PMID:30390", "title": "[Nisin formation by immobilized cells of the lactic acid bacterium, Streptococcus lactis].", "content": "The problem of microbial cell immobilization at present attracts the ever increasing attention of the scientists, since such organisms may be the source of various enzymes. Production of nizin by the immobilized cells of Str. lactis was studied. It was found that the cells of Str. lactis incorporated into polyacrylamide gel produced nizit on definite media. Still, the amount of the antibiotic was 2-3 times lower than in case of using free cells. The effect of a number of factors on the process of immobilization was studied and the influence of some factors, such as temperature, pH, aeration on nizin synthesis by the immobilized cells of the streptococcus was elucidated. Optimal conditions for nizin biosynthesis by the immobilized cells of Str. lactis were developed.", "contents": "[Nisin formation by immobilized cells of the lactic acid bacterium, Streptococcus lactis]. The problem of microbial cell immobilization at present attracts the ever increasing attention of the scientists, since such organisms may be the source of various enzymes. Production of nizin by the immobilized cells of Str. lactis was studied. It was found that the cells of Str. lactis incorporated into polyacrylamide gel produced nizit on definite media. Still, the amount of the antibiotic was 2-3 times lower than in case of using free cells. The effect of a number of factors on the process of immobilization was studied and the influence of some factors, such as temperature, pH, aeration on nizin synthesis by the immobilized cells of the streptococcus was elucidated. Optimal conditions for nizin biosynthesis by the immobilized cells of Str. lactis were developed."}
{"id": "PMID:30391", "title": "Efficiency of beef extract for the recovery of poliovirus from wastewater effluents.", "content": "The efficiency of poliovirus elution from fiber glass cartridge filters (K27), epoxy-fiber glass-asbestos filters (M780), and pleated cartridge filters was assessed by using 3% beef extract (pH 9.0) or 0.1 M glycine (pH 11.5). Poliovirus type I, strain LSc, was seeded into 20- to 25-gallon (ca. 75.6- to 95.6-liter) samples of treated sewage effluent and concentrated by using a filter adsorption-elution technique. Virus elution was accomplished by using either two 600-ml portions of 3% beef extract (pH 9.0), or two 1-liter portions of 0.1 M glycine (pH 11.5). In all experiments, beef extract elution followed by organic flocculation was found to be superior, yielding a mean recovery efficiency of 85%, with recoveries ranging from 68 to 100%. Elution with 0.1 M glycine (pH 11.5) followed by inorganic flocculation resulted in a mean recovery efficiency of 36%. The variable range of recoveries with beef extract could not be significantly improved by varying the type of beef extract or by extending the elution time to 30 min. Second-step reconcentration of 1-liter seeded sewage effluent and renovated wastewater samples indicated that organic flocculation was a more efficient method for virus recovery than inorganic flocculation. Beef extract concentrations of less than 3% were found to be efficient in the recovery of poliovirus from renovated wastewater.", "contents": "Efficiency of beef extract for the recovery of poliovirus from wastewater effluents. The efficiency of poliovirus elution from fiber glass cartridge filters (K27), epoxy-fiber glass-asbestos filters (M780), and pleated cartridge filters was assessed by using 3% beef extract (pH 9.0) or 0.1 M glycine (pH 11.5). Poliovirus type I, strain LSc, was seeded into 20- to 25-gallon (ca. 75.6- to 95.6-liter) samples of treated sewage effluent and concentrated by using a filter adsorption-elution technique. Virus elution was accomplished by using either two 600-ml portions of 3% beef extract (pH 9.0), or two 1-liter portions of 0.1 M glycine (pH 11.5). In all experiments, beef extract elution followed by organic flocculation was found to be superior, yielding a mean recovery efficiency of 85%, with recoveries ranging from 68 to 100%. Elution with 0.1 M glycine (pH 11.5) followed by inorganic flocculation resulted in a mean recovery efficiency of 36%. The variable range of recoveries with beef extract could not be significantly improved by varying the type of beef extract or by extending the elution time to 30 min. Second-step reconcentration of 1-liter seeded sewage effluent and renovated wastewater samples indicated that organic flocculation was a more efficient method for virus recovery than inorganic flocculation. Beef extract concentrations of less than 3% were found to be efficient in the recovery of poliovirus from renovated wastewater."}
{"id": "PMID:30420", "title": "Protection of rats from compound 48/80-induced lethality. A simple test for inhibitors of mast cell-mediated shock.", "content": "The dose of 0.5 mg/kg i.v. of compound 48/80 was lethal in 97.2% of the injected rats. Observations before death and at autopsy were in accordance with the basic effect of compound 48/80 in rats i.e. the sustained release of mast cell mediators, whose action on the cardiovascular system leads to circulatory collapse. The administration of drugs with various pharmacological effects before the intravenous challenge with compound 48/80 allowed us to conclude that the following effects are not sufficient to prevent the lethal shock: inhibition of prostaglandin biosynthesis; H2-histamine antagonism; cholinergic, alpha- or beta-adrenergic blockade; beta-adrenergic stimulation; CNS-effects of antidepressants, hypnotics, sedatives, neuroleptics or narcotic analgesics; ganglion blockade; glucocorticoid or cromoglycate-like activity. Dose-dependent protection from the lethal reaction was obtained with compounds known to exert a single or several actions of the following types: oxatomide-like inhibition of mast cell mediator release; h1-histamine antagonism; serotonin antagonism. Quantitatively, however, when measured in in vitro systems these effects are poorly related to the protection from lethal compound 48/80 challenge. The new test offers the advantage of a simple, comprehensive measure of the potency of a compound to prevent mast cell-mediated shock.", "contents": "Protection of rats from compound 48/80-induced lethality. A simple test for inhibitors of mast cell-mediated shock. The dose of 0.5 mg/kg i.v. of compound 48/80 was lethal in 97.2% of the injected rats. Observations before death and at autopsy were in accordance with the basic effect of compound 48/80 in rats i.e. the sustained release of mast cell mediators, whose action on the cardiovascular system leads to circulatory collapse. The administration of drugs with various pharmacological effects before the intravenous challenge with compound 48/80 allowed us to conclude that the following effects are not sufficient to prevent the lethal shock: inhibition of prostaglandin biosynthesis; H2-histamine antagonism; cholinergic, alpha- or beta-adrenergic blockade; beta-adrenergic stimulation; CNS-effects of antidepressants, hypnotics, sedatives, neuroleptics or narcotic analgesics; ganglion blockade; glucocorticoid or cromoglycate-like activity. Dose-dependent protection from the lethal reaction was obtained with compounds known to exert a single or several actions of the following types: oxatomide-like inhibition of mast cell mediator release; h1-histamine antagonism; serotonin antagonism. Quantitatively, however, when measured in in vitro systems these effects are poorly related to the protection from lethal compound 48/80 challenge. The new test offers the advantage of a simple, comprehensive measure of the potency of a compound to prevent mast cell-mediated shock."}
{"id": "PMID:30421", "title": "Anticholinesterase activity of some butyrophenones.", "content": "The anticholinesterase (antiChE) activity of haloperidol, droperidol and trifluperidol was studied by employing dog plasma as a cholinesterase source and changes in arterial blood pressure, elecited by a mixture of acetylcholine (Ach) and dog plasma with or without those drugs, as an indicator of their antiChE activity. When butyrophenones were present in concentrations of 0.5 up to 5 X 10(-4)M in plasma containing Ach the hypotensive effect of the latter was preserved. Such findings provide experimental evidence that butyrophenones may exert antiChE activity.", "contents": "Anticholinesterase activity of some butyrophenones. The anticholinesterase (antiChE) activity of haloperidol, droperidol and trifluperidol was studied by employing dog plasma as a cholinesterase source and changes in arterial blood pressure, elecited by a mixture of acetylcholine (Ach) and dog plasma with or without those drugs, as an indicator of their antiChE activity. When butyrophenones were present in concentrations of 0.5 up to 5 X 10(-4)M in plasma containing Ach the hypotensive effect of the latter was preserved. Such findings provide experimental evidence that butyrophenones may exert antiChE activity."}
{"id": "PMID:30422", "title": "Effects of indenolol (YB-2), a new beta-adrenergic blocking agent, and its dextro isomer on the central nervous system of mice and rabbits.", "content": "Central depressant actions of a new beta-adrenergic blocking agent, indenolol (YB-2), and its dextro isomer were studied in mice and rabbits. d-Indenolol was less active than dl-indenolol in lowering of methamphetamine group toxicity and calming of fighting behavior, though muscle relaxant, hypolocomotive and anticonvulsant effects of d-indenolol were virtually equal to those of the racemate. dl-Propranolol showed a similar profile of central depressant actions to dl-indenolol, whereas dl-practolol revealed no significant central effects in mice. The dose-response relationship between beta-blocking and central effects in the same animal species suggested that both taming and anti-methamphetamine group toxicity effects of dl-indenolol s.c. do not directly relate to either the peripheral beta-blocking or the membrane stabilizing activity. Intravenous as well as intracerebroventricular administration of dl-indenolol resulted in suppression of pressor responses to the electrical stimulation of the brain stem of unanesthetized rabbits. Neither d-indenolol nor dl-practolol was effective against the pressor responses, suggesting that these two compounds acted on the CNS in a manner different from dl-indenolol even when intracerebroventricularly administered. A possible central beta-adrenergic blocking effect of dl-indenolol was discussed in the light of mechanisms of an antihypertensive action of this compound.", "contents": "Effects of indenolol (YB-2), a new beta-adrenergic blocking agent, and its dextro isomer on the central nervous system of mice and rabbits. Central depressant actions of a new beta-adrenergic blocking agent, indenolol (YB-2), and its dextro isomer were studied in mice and rabbits. d-Indenolol was less active than dl-indenolol in lowering of methamphetamine group toxicity and calming of fighting behavior, though muscle relaxant, hypolocomotive and anticonvulsant effects of d-indenolol were virtually equal to those of the racemate. dl-Propranolol showed a similar profile of central depressant actions to dl-indenolol, whereas dl-practolol revealed no significant central effects in mice. The dose-response relationship between beta-blocking and central effects in the same animal species suggested that both taming and anti-methamphetamine group toxicity effects of dl-indenolol s.c. do not directly relate to either the peripheral beta-blocking or the membrane stabilizing activity. Intravenous as well as intracerebroventricular administration of dl-indenolol resulted in suppression of pressor responses to the electrical stimulation of the brain stem of unanesthetized rabbits. Neither d-indenolol nor dl-practolol was effective against the pressor responses, suggesting that these two compounds acted on the CNS in a manner different from dl-indenolol even when intracerebroventricularly administered. A possible central beta-adrenergic blocking effect of dl-indenolol was discussed in the light of mechanisms of an antihypertensive action of this compound."}
{"id": "PMID:30418", "title": "[Experimental analysis of interference between alpha-adrenergic stimulants with anti-hypertensive activity and the narcotic activity of pentobarbital].", "content": "The interactions of 3 classical alpha-adrenergic antihypertensives of prevalently central type (St 155 or clonidine St 600; BR 750 or guanabenz) with the narcotic effects of pentobarbital have been investigated in the Mus musculus. Interferences between convulsant drugs and spontaneous and coordinatory motor activity were also analysed in comparative studies.", "contents": "[Experimental analysis of interference between alpha-adrenergic stimulants with anti-hypertensive activity and the narcotic activity of pentobarbital]. The interactions of 3 classical alpha-adrenergic antihypertensives of prevalently central type (St 155 or clonidine St 600; BR 750 or guanabenz) with the narcotic effects of pentobarbital have been investigated in the Mus musculus. Interferences between convulsant drugs and spontaneous and coordinatory motor activity were also analysed in comparative studies."}
{"id": "PMID:30423", "title": "Influence of aminophylline or beta-adrenoceptor blockade on glucagon release by a vasoactive adenosine analogue.", "content": "The glucagon-releasing activity of adenosine-5'-ethyl-carboxamide (744-96) was studied in conscious dogs pretreated either with aminophylline or with bupranolol, a beta-adrenoceptor blocking drug. The adenosine antagonist, aminophylline, inhibited both the glucagon-releasing and the blood pressure lowering effects of 744-96 (10 microgram/kg i.v.). The actions of the adenosine analogue on glucagon release and haemodynamics were not affected by bupranolol pretreatment. These results indicate that the adenosine analogue mediates glucagon release by interaction with so-called adenosine receptors. A beta-adrenoceptor mediated release secondary to 744-96-induced hypotension and baroreceptor-activation can be excluded.", "contents": "Influence of aminophylline or beta-adrenoceptor blockade on glucagon release by a vasoactive adenosine analogue. The glucagon-releasing activity of adenosine-5'-ethyl-carboxamide (744-96) was studied in conscious dogs pretreated either with aminophylline or with bupranolol, a beta-adrenoceptor blocking drug. The adenosine antagonist, aminophylline, inhibited both the glucagon-releasing and the blood pressure lowering effects of 744-96 (10 microgram/kg i.v.). The actions of the adenosine analogue on glucagon release and haemodynamics were not affected by bupranolol pretreatment. These results indicate that the adenosine analogue mediates glucagon release by interaction with so-called adenosine receptors. A beta-adrenoceptor mediated release secondary to 744-96-induced hypotension and baroreceptor-activation can be excluded."}
{"id": "PMID:30425", "title": "[Importance of measuring blood volume by an isotope method in essential hypertension].", "content": "Measurement of the blood volume in cases of essential hypertension has shown a negative correlation with increase in blood pressure. We have been able to distinguish a group of moderate hypertensives who are hypervolemic, and whose systemic effect is more marked than in the moderate hypovolemic type. Such cases respond poorly to single drug therapy with beta blockers, but well to diuretics. The authors propose a general treatment scheme for essential hypertension: single therapy (beta blockers or diuretics) in mild cases of hypertension; single therapy by diuretics in the moderate types with the increased volume; single therapy by beta blockers in the moderate types with low volume, multiple treatment with the drugs together in cases of severe hypertension.", "contents": "[Importance of measuring blood volume by an isotope method in essential hypertension]. Measurement of the blood volume in cases of essential hypertension has shown a negative correlation with increase in blood pressure. We have been able to distinguish a group of moderate hypertensives who are hypervolemic, and whose systemic effect is more marked than in the moderate hypovolemic type. Such cases respond poorly to single drug therapy with beta blockers, but well to diuretics. The authors propose a general treatment scheme for essential hypertension: single therapy (beta blockers or diuretics) in mild cases of hypertension; single therapy by diuretics in the moderate types with the increased volume; single therapy by beta blockers in the moderate types with low volume, multiple treatment with the drugs together in cases of severe hypertension."}
{"id": "PMID:30426", "title": "Neuroleptic-induced prolactin level elevation and breast cancer: an emerging clinical issue.", "content": "This article reviews the evidence that neuroleptics may increase the risk of breast cancer via their effects on prolactin secretion. All available neuroleptics, including reserpine, raise serum prolactin levels. Elevated serum prolactin level increases the incidence of spontaneously occurring mammary tumors in mice, and increases the growth of established carcinogen-induced mammary tumors in rats. Caution is necessary in extrapolating this relationship to human mammary tumors because human and rodent tumors differ in some important characteristics, including hormone responsiveness. Serum prolactin levels in women with, or at risk for, breast cancer have generally been normal, and only a minority of human mammary tumors respond to changes in serum prolactin levels. Epidemiologic studies have failed to demonstrate an increased risk of breast cancer associated with the use of neuroleptics or reserpine. Thus, although some human mammary tumors are prolactin dependent, the available evidence does not demonstrate an increased risk of breast cancer in women receiving neuroleptics. We conclude that (1) additional epidemiologic studies of the incidence of mammary tumors in women treated with neuroleptics are desirable; (2) it is premature to mandate warning patients of an unknown and undemonstrated increase in the risk of developing breast cancer associated with neuroleptic treatment; (3) detection of existing mammary tumors by breast examination prior to administration of neuroleptics is desirable; and (4) development of antipsychotic drugs that do not increase serum prolactin level may be indicated.", "contents": "Neuroleptic-induced prolactin level elevation and breast cancer: an emerging clinical issue. This article reviews the evidence that neuroleptics may increase the risk of breast cancer via their effects on prolactin secretion. All available neuroleptics, including reserpine, raise serum prolactin levels. Elevated serum prolactin level increases the incidence of spontaneously occurring mammary tumors in mice, and increases the growth of established carcinogen-induced mammary tumors in rats. Caution is necessary in extrapolating this relationship to human mammary tumors because human and rodent tumors differ in some important characteristics, including hormone responsiveness. Serum prolactin levels in women with, or at risk for, breast cancer have generally been normal, and only a minority of human mammary tumors respond to changes in serum prolactin levels. Epidemiologic studies have failed to demonstrate an increased risk of breast cancer associated with the use of neuroleptics or reserpine. Thus, although some human mammary tumors are prolactin dependent, the available evidence does not demonstrate an increased risk of breast cancer in women receiving neuroleptics. We conclude that (1) additional epidemiologic studies of the incidence of mammary tumors in women treated with neuroleptics are desirable; (2) it is premature to mandate warning patients of an unknown and undemonstrated increase in the risk of developing breast cancer associated with neuroleptic treatment; (3) detection of existing mammary tumors by breast examination prior to administration of neuroleptics is desirable; and (4) development of antipsychotic drugs that do not increase serum prolactin level may be indicated."}
{"id": "PMID:30427", "title": "Delusional unipolar depression: description and drug response.", "content": "This retrospective study describes the response of 13 delusional unipolar depressives to combination antipsychotic-tricyclic antidepressant drug therapy. The Research Diagnostic Criteria were used by two independent raters to verify the presence of a delusional, primary, unipolar, major depressive disorder. Thirteen patients met the criteria and received combined antipsychotic-antidepressant pharmacotherapy. Twelve of the 13 responded. This contrasts sharply with the low response rate described for delusional depressives when treated with tricyclic antidepressants alone. Descriptive characteristics of the delusional depressives were compared with those of a group of nondelusional unipolar depressives. Delusional depressives had histories of a greater number of prior depressive episodes and more of the delusional depressives demonstrated a psychomotor disturbance.", "contents": "Delusional unipolar depression: description and drug response. This retrospective study describes the response of 13 delusional unipolar depressives to combination antipsychotic-tricyclic antidepressant drug therapy. The Research Diagnostic Criteria were used by two independent raters to verify the presence of a delusional, primary, unipolar, major depressive disorder. Thirteen patients met the criteria and received combined antipsychotic-antidepressant pharmacotherapy. Twelve of the 13 responded. This contrasts sharply with the low response rate described for delusional depressives when treated with tricyclic antidepressants alone. Descriptive characteristics of the delusional depressives were compared with those of a group of nondelusional unipolar depressives. Delusional depressives had histories of a greater number of prior depressive episodes and more of the delusional depressives demonstrated a psychomotor disturbance."}
{"id": "PMID:30428", "title": "Benzodiazepines in depressive disorders.", "content": "Some investigators have found benzodiazepines effective in the treatment of anxious depression and thus have argued that benzodiazepines were \"antidepressants.\" We reviewed the literature on benzodiazepines in depressive disorders. Comparative studies indicate they are less effective than standard antidepressants in the treatment of several types of depressive illnesses. Although they display definite anxiolytic properties and may elevate mood, they exert limited effect on the core symptoms of endogenous depression. An argument is made that benzodiazepines are primarily anxiolytic rather than antidepressant.", "contents": "Benzodiazepines in depressive disorders. Some investigators have found benzodiazepines effective in the treatment of anxious depression and thus have argued that benzodiazepines were \"antidepressants.\" We reviewed the literature on benzodiazepines in depressive disorders. Comparative studies indicate they are less effective than standard antidepressants in the treatment of several types of depressive illnesses. Although they display definite anxiolytic properties and may elevate mood, they exert limited effect on the core symptoms of endogenous depression. An argument is made that benzodiazepines are primarily anxiolytic rather than antidepressant."}
{"id": "PMID:30429", "title": "Use of antidepressant drugs in schizophrenia.", "content": "This review surveys the therapeutic efficacy of tricyclic antidepressants and monoamine oxidase inhibitors in schizophrenic patients. In general, the use of these drugs alone was found not to be warranted in schizophrenia, except perhaps in the so-called pseudoneurotic subgroup. In most cases, combinations of antidepressants and phenothiazines were not more beneficial than phenothiazines alone. In particular, the conditions of agitated patients and patients with histories of social deviance dating back to childhood were often made worse by the addition of an antidepressant. However, when the patients who demonstrated symptoms of clinical depression other than anergia were isolated from several of these studies, it was found that they constituted a subgroup that was often benefited by use of these combinations. Favorable and unfavorable clinical response patterns are discussed, and recommendations for future research are outlined.", "contents": "Use of antidepressant drugs in schizophrenia. This review surveys the therapeutic efficacy of tricyclic antidepressants and monoamine oxidase inhibitors in schizophrenic patients. In general, the use of these drugs alone was found not to be warranted in schizophrenia, except perhaps in the so-called pseudoneurotic subgroup. In most cases, combinations of antidepressants and phenothiazines were not more beneficial than phenothiazines alone. In particular, the conditions of agitated patients and patients with histories of social deviance dating back to childhood were often made worse by the addition of an antidepressant. However, when the patients who demonstrated symptoms of clinical depression other than anergia were isolated from several of these studies, it was found that they constituted a subgroup that was often benefited by use of these combinations. Favorable and unfavorable clinical response patterns are discussed, and recommendations for future research are outlined."}
{"id": "PMID:30430", "title": "The effect of methylphenidate on serum growth hormone: influence of antipsychotic drugs and diagnosis.", "content": "Intravenously administered methylphenidate, 0.5 mg/kg, causes a consistent rise in human serum growth hormone level, with peak values usually occurring 30 minutes after infusion. This rise is attenuated in patients receiving various antipsychotic medications administered on a long-term basis and is decreased in schizophrenic and drug-dependent patients. Methylphenidate causes increases in talkativeness, blood pressure, and pulse that generally parallel increases in serum growth hormone level. However, in contrast to the methylphenidate-induced rise in serum growth hormone level, methylphenidate-induced changes in cardiovascular variables and talkativeness are not altered by antipsychotic medications or diagnostic classification.", "contents": "The effect of methylphenidate on serum growth hormone: influence of antipsychotic drugs and diagnosis. Intravenously administered methylphenidate, 0.5 mg/kg, causes a consistent rise in human serum growth hormone level, with peak values usually occurring 30 minutes after infusion. This rise is attenuated in patients receiving various antipsychotic medications administered on a long-term basis and is decreased in schizophrenic and drug-dependent patients. Methylphenidate causes increases in talkativeness, blood pressure, and pulse that generally parallel increases in serum growth hormone level. However, in contrast to the methylphenidate-induced rise in serum growth hormone level, methylphenidate-induced changes in cardiovascular variables and talkativeness are not altered by antipsychotic medications or diagnostic classification."}
{"id": "PMID:30431", "title": "Clinical significance of an increased or decreased serum alkaline phosphatase level.", "content": "An increase in the level of serum alkaline phosphatase (ALP) may be caused by a wide variety of pathologic lesions that involve multiple organs, since the enzyme is an ubiquitous one. Before one attempts to identify a significant pathologic abnormality, the clinician should consider the possibility of a physiologic or spurious cause for an increased level of ALP. A decreased ALP level also has diagnostic value.", "contents": "Clinical significance of an increased or decreased serum alkaline phosphatase level. An increase in the level of serum alkaline phosphatase (ALP) may be caused by a wide variety of pathologic lesions that involve multiple organs, since the enzyme is an ubiquitous one. Before one attempts to identify a significant pathologic abnormality, the clinician should consider the possibility of a physiologic or spurious cause for an increased level of ALP. A decreased ALP level also has diagnostic value."}
{"id": "PMID:30433", "title": "Metal chelate affinity chromatography of hamster interferon.", "content": "Syrian hamster interferon, produced by benzo(a)pyrene-transformed embryo cells does not display an affinity for Zn++ chelate-agarose. However, the interferon binds to Cu++ chelate-agarose and can be displaced from the column by a falling pH-gradient. The chromatography of crude hamster interferon preparation on a tandem of columsn: Zn++ chelate-agarose in equilibrium Cu++ chelate-agarose results in a 25-fold purification of interferon.", "contents": "Metal chelate affinity chromatography of hamster interferon. Syrian hamster interferon, produced by benzo(a)pyrene-transformed embryo cells does not display an affinity for Zn++ chelate-agarose. However, the interferon binds to Cu++ chelate-agarose and can be displaced from the column by a falling pH-gradient. The chromatography of crude hamster interferon preparation on a tandem of columsn: Zn++ chelate-agarose in equilibrium Cu++ chelate-agarose results in a 25-fold purification of interferon."}
{"id": "PMID:30438", "title": "Orthodontic seminar: a realistic approach construction, adjustment and repair of appliances.", "content": "Details of the design and construction of removable and simple fixed appliances are presented. Equipment, instruments, and supplies are listed. Welding, soldering, banding and bonding are illustrated. Finally, step-by-step descriptions are given of first aid measures for the repair of fixed appliances applicable to the general practice situation.", "contents": "Orthodontic seminar: a realistic approach construction, adjustment and repair of appliances. Details of the design and construction of removable and simple fixed appliances are presented. Equipment, instruments, and supplies are listed. Welding, soldering, banding and bonding are illustrated. Finally, step-by-step descriptions are given of first aid measures for the repair of fixed appliances applicable to the general practice situation."}
{"id": "PMID:30439", "title": "Myocardial infarction--the problems and prognosis: Paper 1.", "content": "Deaths from coronary heart disease and myocardial infarct may occur in previously undiagnosed subjects (the so called pre-hospital phase), in hospital following admission to a coronary care unit, or following discharge. Mortality in the pre-hospital phase has been estimated at 35--40 per cent. Within Australia the mortality in the coronary care unit is 11--17 per cent. Following discharge, the mortality is about 20 per cent in the first 12 months and then occurs at about four to five per cent per year for the first five years.", "contents": "Myocardial infarction--the problems and prognosis: Paper 1. Deaths from coronary heart disease and myocardial infarct may occur in previously undiagnosed subjects (the so called pre-hospital phase), in hospital following admission to a coronary care unit, or following discharge. Mortality in the pre-hospital phase has been estimated at 35--40 per cent. Within Australia the mortality in the coronary care unit is 11--17 per cent. Following discharge, the mortality is about 20 per cent in the first 12 months and then occurs at about four to five per cent per year for the first five years."}
{"id": "PMID:30440", "title": "Factors influencing the infarct: the place of beta-blockade in limiting infarct size.", "content": "The mechanisms whereby myocardial infarction in man is precipitated are not understood--largely because the event is usually well established by the time medical help is called, but also because the techniques available have not yet permitted analysis of the earliest changes. On the other hand, the consequences of myocardial infarction for the heart and circulation are now well understood, and the need for therapy better appreciated.", "contents": "Factors influencing the infarct: the place of beta-blockade in limiting infarct size. The mechanisms whereby myocardial infarction in man is precipitated are not understood--largely because the event is usually well established by the time medical help is called, but also because the techniques available have not yet permitted analysis of the earliest changes. On the other hand, the consequences of myocardial infarction for the heart and circulation are now well understood, and the need for therapy better appreciated."}
{"id": "PMID:30441", "title": "The role of long term beta-blockade after myocardial infarction: Paper 1.", "content": "The opinion is emerging that beta-blocking drugs have an important role in management of patients following acute myocardial infarction. Already beta-blocking drugs are accepted as the treatment of choice in hypertension and in angina pectoris--in the major risk factor and consequence respectively of coronary atherosclerosis, and both commonly recognized in patients who survive acute myocardial infarction. But beta-blocking drugs also may be of benefit in reducing the incidence and risk of subsequent infarction, and so may be of value for long term treatment of patients who have no symptoms whatever following acute infarction.", "contents": "The role of long term beta-blockade after myocardial infarction: Paper 1. The opinion is emerging that beta-blocking drugs have an important role in management of patients following acute myocardial infarction. Already beta-blocking drugs are accepted as the treatment of choice in hypertension and in angina pectoris--in the major risk factor and consequence respectively of coronary atherosclerosis, and both commonly recognized in patients who survive acute myocardial infarction. But beta-blocking drugs also may be of benefit in reducing the incidence and risk of subsequent infarction, and so may be of value for long term treatment of patients who have no symptoms whatever following acute infarction."}
{"id": "PMID:30442", "title": "The role of long term beta-blockade after myocardial infarction: Paper 2.", "content": "Acute myocardial infarction is associated with pain, tissue damage and circulatory impairment. As a result of these changes, there is increased sympathetic drive to the heart in the form of increased sympathetic nerve activity and increased circulating catecholamines.", "contents": "The role of long term beta-blockade after myocardial infarction: Paper 2. Acute myocardial infarction is associated with pain, tissue damage and circulatory impairment. As a result of these changes, there is increased sympathetic drive to the heart in the form of increased sympathetic nerve activity and increased circulating catecholamines."}
{"id": "PMID:30443", "title": "The role of long term beta-blockade after myocardial infarction: Paper 3.", "content": "For many years the search has gone on for suitable drug therapy to improve survival following myocardial infarction. Most recently, beta-adrenergic blockade has entered the lists. Naturally beta-blockade is used in the conventional way to combat angina pectoris following an infarct, and one can expect that 70 per cent of patients will obtain significant relief.", "contents": "The role of long term beta-blockade after myocardial infarction: Paper 3. For many years the search has gone on for suitable drug therapy to improve survival following myocardial infarction. Most recently, beta-adrenergic blockade has entered the lists. Naturally beta-blockade is used in the conventional way to combat angina pectoris following an infarct, and one can expect that 70 per cent of patients will obtain significant relief."}
{"id": "PMID:30444", "title": "The role of long term beta-blockade after myocardial infarction: Paper 4.", "content": "The place of beta-blockade following myocardial infarction should be considered in two phases; the acute infarction, and the long term management after infarction.", "contents": "The role of long term beta-blockade after myocardial infarction: Paper 4. The place of beta-blockade following myocardial infarction should be considered in two phases; the acute infarction, and the long term management after infarction."}
{"id": "PMID:30445", "title": "Susceptibility of orbiviruses to low pH and to organic solvents.", "content": "Six orbiviruses, Corriparta, Wallal, Eubenangee, D'Aguilar, Warrego and Mitchell River, were inactivated within 30 min in solutions of pH less than 6. All but Wallal virus resisted treatment with ether at 1 degrees for 22 h but only Corriparta virus resisted treatment with chloroform at 1 degrees for 22 h. The genomes of the orbiviruses, including Corriparta virus, after electrophoresis in acrylamide gels separated into basically similar patterns which were distinct from the pattern of reovirus RNA.", "contents": "Susceptibility of orbiviruses to low pH and to organic solvents. Six orbiviruses, Corriparta, Wallal, Eubenangee, D'Aguilar, Warrego and Mitchell River, were inactivated within 30 min in solutions of pH less than 6. All but Wallal virus resisted treatment with ether at 1 degrees for 22 h but only Corriparta virus resisted treatment with chloroform at 1 degrees for 22 h. The genomes of the orbiviruses, including Corriparta virus, after electrophoresis in acrylamide gels separated into basically similar patterns which were distinct from the pattern of reovirus RNA."}
{"id": "PMID:30447", "title": "Kinetics and reaction mechanism of potassium-activated aldehyde dehydrogenase from Saccharomyces cerevisiae.", "content": "Data from steady-state kinetic analysis of yeast K+-activated aldehyde dehydrogenase are consistent with a ternary complex mechanism. Evidence from alternative substrate analysis and product-inhibition studies supports an ordered sequence of substrate binding in which NAD+ is the leading substrate. A preincubation requirement for NAD+ for maximum activity is also consistent with the importance of a binary enzyme-NAD+ complex. Dissociation constant for enzyme-NAD+ complex determined kinetically is in reasonable agreement with that determined by direct binding. The order of substrate addition proposed here differs from that proposed for a yeast aldehyde dehydrogenase previously reported. Different methods of purification produced an enzyme that showed similar kinetic characteristics to those reported here.", "contents": "Kinetics and reaction mechanism of potassium-activated aldehyde dehydrogenase from Saccharomyces cerevisiae. Data from steady-state kinetic analysis of yeast K+-activated aldehyde dehydrogenase are consistent with a ternary complex mechanism. Evidence from alternative substrate analysis and product-inhibition studies supports an ordered sequence of substrate binding in which NAD+ is the leading substrate. A preincubation requirement for NAD+ for maximum activity is also consistent with the importance of a binary enzyme-NAD+ complex. Dissociation constant for enzyme-NAD+ complex determined kinetically is in reasonable agreement with that determined by direct binding. The order of substrate addition proposed here differs from that proposed for a yeast aldehyde dehydrogenase previously reported. Different methods of purification produced an enzyme that showed similar kinetic characteristics to those reported here."}
{"id": "PMID:30448", "title": "Electron-paramagnetic-resonance studies on the redox properties of the molybdenum-iron protein of nitrogenase between +50 and -450 mV.", "content": "The midpoint potentials, Em, for the oxidation of the characteristic e.p.r. signal with g values near 4.3, 3.7 and 2.01, of the nitrogenase Mo-Fe proteins from a number of bacteria were measured. They were 0mV for Clostridium pasteurianum, -42mV for Azotobacter chroococcum and Azotobacter vinelandii, -95mV for Bacillus polymyxa and -180mV for Klebsiella pneumoniae Mo-Fe proteins at pH 7.9. The oxidations were thermodynamically reversible for the proteins from A. chroococcum, A. vinelandii and K. pneumoniae and the Em was independent of protein activity for this last protein. The protein from C. pasteurianum required a lower potential for reduction than for oxidation, and the oxidation of the protein from B. polymyxa was only 70% reversible. The apparent Em of the latter protein was decreased by 40mV in the presence of 60mM-MgCl2. The pH-dependence of the Em of the protein from K. pneumoniae was interpreted in terms of a single ionization, not directly associated with the e.p.r.-active centre, with a pKa of 7.0 in the oxidized form of the protein and a pH-independent region at low pH (Em = 118 +/- 6.3 mV). Approx. 20% increase in activity after oxidation was observed for the proteins from B. polymyxa, A. chroococcum and K. pneumoniae. The significance of the above results and their relationship to other published data are discussed.", "contents": "Electron-paramagnetic-resonance studies on the redox properties of the molybdenum-iron protein of nitrogenase between +50 and -450 mV. The midpoint potentials, Em, for the oxidation of the characteristic e.p.r. signal with g values near 4.3, 3.7 and 2.01, of the nitrogenase Mo-Fe proteins from a number of bacteria were measured. They were 0mV for Clostridium pasteurianum, -42mV for Azotobacter chroococcum and Azotobacter vinelandii, -95mV for Bacillus polymyxa and -180mV for Klebsiella pneumoniae Mo-Fe proteins at pH 7.9. The oxidations were thermodynamically reversible for the proteins from A. chroococcum, A. vinelandii and K. pneumoniae and the Em was independent of protein activity for this last protein. The protein from C. pasteurianum required a lower potential for reduction than for oxidation, and the oxidation of the protein from B. polymyxa was only 70% reversible. The apparent Em of the latter protein was decreased by 40mV in the presence of 60mM-MgCl2. The pH-dependence of the Em of the protein from K. pneumoniae was interpreted in terms of a single ionization, not directly associated with the e.p.r.-active centre, with a pKa of 7.0 in the oxidized form of the protein and a pH-independent region at low pH (Em = 118 +/- 6.3 mV). Approx. 20% increase in activity after oxidation was observed for the proteins from B. polymyxa, A. chroococcum and K. pneumoniae. The significance of the above results and their relationship to other published data are discussed."}
{"id": "PMID:30449", "title": "Elastin cross-linking in vitro. Studies on factors influencing the formation of desmosines by lysyl oxidase action on tropoelastin.", "content": "The formation of isodesmosine and desmosine in vitro by the action of lysyl oxidase on tropoelastin was studied. The synthesis of desmosines occurred in the absence of additional substances. The formation of desmosines was not affected by removal of molecular O2 from the reaction medium nor was it affected by the lack of proline hydroxylation in tropoelastin. However, there was virtually no desmosine formation at 15 degrees C, a temperature not conducive to coacervation, indicating that coacervation is an important prerequisite for cross-linking.", "contents": "Elastin cross-linking in vitro. Studies on factors influencing the formation of desmosines by lysyl oxidase action on tropoelastin. The formation of isodesmosine and desmosine in vitro by the action of lysyl oxidase on tropoelastin was studied. The synthesis of desmosines occurred in the absence of additional substances. The formation of desmosines was not affected by removal of molecular O2 from the reaction medium nor was it affected by the lack of proline hydroxylation in tropoelastin. However, there was virtually no desmosine formation at 15 degrees C, a temperature not conducive to coacervation, indicating that coacervation is an important prerequisite for cross-linking."}
{"id": "PMID:30450", "title": "Some properties of 3-hydroxy-3-methylglutaryl-coenzyme A synthase from ox liver.", "content": "Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5) was purified from ox liver, and obtained essentially free from 3-oxoacyl-CoA thiolases. The kinetic behaviour, like that of the synthases from chicken liver and yeast, is compatible with a reaction pathway involving condensation of an acetyl-enzyme with acetoacetyl-CoA. The Km for acetoacetyl-CoA, less than 1 micronM at pH 7.8, may possibly be low enough to permit rapid ketogenesis under physiological conditions without the need for a binary complex between the synthase and oxoacyl-CoA thiolase.", "contents": "Some properties of 3-hydroxy-3-methylglutaryl-coenzyme A synthase from ox liver. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5) was purified from ox liver, and obtained essentially free from 3-oxoacyl-CoA thiolases. The kinetic behaviour, like that of the synthases from chicken liver and yeast, is compatible with a reaction pathway involving condensation of an acetyl-enzyme with acetoacetyl-CoA. The Km for acetoacetyl-CoA, less than 1 micronM at pH 7.8, may possibly be low enough to permit rapid ketogenesis under physiological conditions without the need for a binary complex between the synthase and oxoacyl-CoA thiolase."}
{"id": "PMID:30451", "title": "Proteoglycan-degrading enzymes of rabbit fibroblasts and granulocytes.", "content": "A neutral proteinase secreted by rabbit synovial fibroblasts in parallel with specific collagenase was partially purified by ion-exchange chromatography. At pH 7.6 this proteinase degraded 35S-labelled bovine nasal proteoglycan and azo-casein. The enzymic activity was inhibited by EDTA, 1,10-phenanthroline and serum, whereas di-isopropyl phosphorofluoridate and soya-bean trypsin inhibitor had little effect. By gel filtration the apparent mol.wt. of the enzyme was 25000. The fibroblast neutral proteinase was compared with the proteoglycan-degrading neutral proteinases of rabbit polymorphonuclear-leucocyte granules. Two distinct activities were found in the granules: one was inhibited by soya-bean trypsin inhibitor and the other by EDTA. The proteoglycan-degrading proteinases of rabbit fibroblasts and polymorphonuclear leucocytes at acid pH also were examined. Both cathepsin D and a thiol-dependent proteinase contributed to the degradation of proteoglycan at pH 4.5.", "contents": "Proteoglycan-degrading enzymes of rabbit fibroblasts and granulocytes. A neutral proteinase secreted by rabbit synovial fibroblasts in parallel with specific collagenase was partially purified by ion-exchange chromatography. At pH 7.6 this proteinase degraded 35S-labelled bovine nasal proteoglycan and azo-casein. The enzymic activity was inhibited by EDTA, 1,10-phenanthroline and serum, whereas di-isopropyl phosphorofluoridate and soya-bean trypsin inhibitor had little effect. By gel filtration the apparent mol.wt. of the enzyme was 25000. The fibroblast neutral proteinase was compared with the proteoglycan-degrading neutral proteinases of rabbit polymorphonuclear-leucocyte granules. Two distinct activities were found in the granules: one was inhibited by soya-bean trypsin inhibitor and the other by EDTA. The proteoglycan-degrading proteinases of rabbit fibroblasts and polymorphonuclear leucocytes at acid pH also were examined. Both cathepsin D and a thiol-dependent proteinase contributed to the degradation of proteoglycan at pH 4.5."}
{"id": "PMID:30452", "title": "Use of the sulphite adduct of nicotinamide-adenine dinucleotide to study ionizations and the kinetics of lactate dehydrogenase and malate dehydrogenase.", "content": "1. The formation of the non-enzymic adduct of NAD(+) and sulphite was investigated. In agreement with others we conclude that the dianion of sulphite adds to NAD(+). 2. The formation of ternary complexes of either lactate dehydrogenase or malate dehydrogenase with NAD(+) and sulphite was investigated. The u.v. spectrum of the NAD-sulphite adduct was the same whether free or enzyme-bound at either pH6 or pH8. This suggests that the free and enzyme-bound adducts have a similar electronic structure. 3. The effect of pH on the concentration of NAD-sulphite bound to both enzymes was measured in a new titration apparatus. Unlike the non-enzymic adduct (where the stability change with pH simply reflects HSO(3) (-)=SO(3) (2-)+H(+)), the enzyme-bound adduct showed a bell-shaped pH-stability curve, which indicated that an enzyme side chain of pK=6.2 must be protonated for the complex to form. Since the adduct does not bind to the enzyme when histidine-195 of lactate dehydrogenase is ethoxycarbonylated we conclude that the protein group involved is histidine-195. 4. The pH-dependence of the formation of a ternary complex of lactate dehydrogenase, NAD(+) and oxalate suggested that an enzyme group is protonated when this complex forms. 5. The rate at which NAD(+) binds to lactate dehydrogenase and malate dehydrogenase was measured by trapping the enzyme-bound NAD(+) by rapid reaction with sulphite. The rate of NAD(+) dissociation from the enzymes was calculated from the bimolecular association kinetic constant and from the equilibrium binding constant and was in both cases much faster than the forward V(max.). No kinetic evidence was found that suggested that there were interactions between protein subunits on binding NAD(+).", "contents": "Use of the sulphite adduct of nicotinamide-adenine dinucleotide to study ionizations and the kinetics of lactate dehydrogenase and malate dehydrogenase. 1. The formation of the non-enzymic adduct of NAD(+) and sulphite was investigated. In agreement with others we conclude that the dianion of sulphite adds to NAD(+). 2. The formation of ternary complexes of either lactate dehydrogenase or malate dehydrogenase with NAD(+) and sulphite was investigated. The u.v. spectrum of the NAD-sulphite adduct was the same whether free or enzyme-bound at either pH6 or pH8. This suggests that the free and enzyme-bound adducts have a similar electronic structure. 3. The effect of pH on the concentration of NAD-sulphite bound to both enzymes was measured in a new titration apparatus. Unlike the non-enzymic adduct (where the stability change with pH simply reflects HSO(3) (-)=SO(3) (2-)+H(+)), the enzyme-bound adduct showed a bell-shaped pH-stability curve, which indicated that an enzyme side chain of pK=6.2 must be protonated for the complex to form. Since the adduct does not bind to the enzyme when histidine-195 of lactate dehydrogenase is ethoxycarbonylated we conclude that the protein group involved is histidine-195. 4. The pH-dependence of the formation of a ternary complex of lactate dehydrogenase, NAD(+) and oxalate suggested that an enzyme group is protonated when this complex forms. 5. The rate at which NAD(+) binds to lactate dehydrogenase and malate dehydrogenase was measured by trapping the enzyme-bound NAD(+) by rapid reaction with sulphite. The rate of NAD(+) dissociation from the enzymes was calculated from the bimolecular association kinetic constant and from the equilibrium binding constant and was in both cases much faster than the forward V(max.). No kinetic evidence was found that suggested that there were interactions between protein subunits on binding NAD(+)."}
{"id": "PMID:30453", "title": "Biochemical applications of chemically induced nuclear polarization in phenols, peptides, catecholamines and related molecules.", "content": "A photochemical method for producing proton nuclear polarization in phenolic biogenic molecules such as tyrosyl polypeptides and phenolic amines is described. The nuclear polarization is due to the reversible hydrogen-atom transfer from the phenolic hydroxy group to triplet photoexcited xanthene-dye molecules. Typical results obtained with insulin, catecholamines and other phenolic molecules are treated in detail.", "contents": "Biochemical applications of chemically induced nuclear polarization in phenols, peptides, catecholamines and related molecules. A photochemical method for producing proton nuclear polarization in phenolic biogenic molecules such as tyrosyl polypeptides and phenolic amines is described. The nuclear polarization is due to the reversible hydrogen-atom transfer from the phenolic hydroxy group to triplet photoexcited xanthene-dye molecules. Typical results obtained with insulin, catecholamines and other phenolic molecules are treated in detail."}
{"id": "PMID:30454", "title": "The pH-dependence of sugar-transport and glycolysis in cultured Ehrlich ascites-tumour cells.", "content": "1. pH-dependence of glycolysis has generally been ascribed to the effects of pH on the activities of glycolytic enzymes. The present study shows that sugar transport is pH-dependent in cultured Ehrlich ascites-tumour cells. 2. The rates of glucose consumption, of 3-O-methylglucose transport, and of 2-deoxyglucose transport and phosphorylation increased as linear functions of pH, as the pH of the cell culture medium was increased from 6.1 to 8.5. Transport of glucose, as measured in ATP-depleted cells, was pH-dependent to the same extent as transport of the non-metabolizable sugars. 3. Glucose consumption rates were about 8-fold higher at pH 8.5 than at pH 6.4. About 65-85% of glucose was converted into lactate. Sugar transport rates were 2.5-fold higher at pH 8.5 than at pH 6.3. 4. pH affected both simple diffusion and facilitated diffusion. pH effect was mainly on the Vmax. of 2-deoxyglucose uptake, and on the rapid-uptake phase of 3-O-methylglucose transport. 5. It was estimated that about 70% of the pH effect on the rates of glucose consumption may be due to the effect on sugar transport and the remainder to the effect on the activities of glycolytic enzymes.", "contents": "The pH-dependence of sugar-transport and glycolysis in cultured Ehrlich ascites-tumour cells. 1. pH-dependence of glycolysis has generally been ascribed to the effects of pH on the activities of glycolytic enzymes. The present study shows that sugar transport is pH-dependent in cultured Ehrlich ascites-tumour cells. 2. The rates of glucose consumption, of 3-O-methylglucose transport, and of 2-deoxyglucose transport and phosphorylation increased as linear functions of pH, as the pH of the cell culture medium was increased from 6.1 to 8.5. Transport of glucose, as measured in ATP-depleted cells, was pH-dependent to the same extent as transport of the non-metabolizable sugars. 3. Glucose consumption rates were about 8-fold higher at pH 8.5 than at pH 6.4. About 65-85% of glucose was converted into lactate. Sugar transport rates were 2.5-fold higher at pH 8.5 than at pH 6.3. 4. pH affected both simple diffusion and facilitated diffusion. pH effect was mainly on the Vmax. of 2-deoxyglucose uptake, and on the rapid-uptake phase of 3-O-methylglucose transport. 5. It was estimated that about 70% of the pH effect on the rates of glucose consumption may be due to the effect on sugar transport and the remainder to the effect on the activities of glycolytic enzymes."}
{"id": "PMID:30461", "title": "Characterization of cholesterol ester hydrolase activities in rabbit and guinea pig aortas.", "content": "Cholesterol ester hydrolase activity was determined in preparations of rabbit and guinea pig aorta utilizing micellar and glycerol-dispersed cholesterol oleate substrates. Both substrate preparations demonstrated an acid pH optimum of 4--5 for the soluble and particulate rabbit media cholesterol ester hydrolase, suggesting a lysosomal origin for this activity. Approximately one-fifth of the total recovered activity was particulate. Particulate media preparations from guinea pig aorta also demonstrated cholesterol ester hydrolase activity at acid pH values with a definite optimum at pH 5 for the glycerol-dispersed substrate. However, in contrast to the rabbit media enzyme, activity was also observed at neutral pH with another optimum at pH 7. The supernatant enzyme from guinea pig media exhibited only a single pH optimum of 7. Cholesterol ester hydrolase activity from either rabbit or guinea pig media was not influenced by preincubation with cyclic AMP, ATP and protein kinase. The addition of chloroquine resulted in the inhibition of both the rabbit and guinea pig enzyme. Cholesterol ester hydrolase activity from rabbit and guinea pig media was also inhibited by phenyl methane sulfonyl fluoride; activity measured at pH 7 (guinea pig) was more sensitive to inhibition than activity measured at pH 5 (guinea pig and rabbit).", "contents": "Characterization of cholesterol ester hydrolase activities in rabbit and guinea pig aortas. Cholesterol ester hydrolase activity was determined in preparations of rabbit and guinea pig aorta utilizing micellar and glycerol-dispersed cholesterol oleate substrates. Both substrate preparations demonstrated an acid pH optimum of 4--5 for the soluble and particulate rabbit media cholesterol ester hydrolase, suggesting a lysosomal origin for this activity. Approximately one-fifth of the total recovered activity was particulate. Particulate media preparations from guinea pig aorta also demonstrated cholesterol ester hydrolase activity at acid pH values with a definite optimum at pH 5 for the glycerol-dispersed substrate. However, in contrast to the rabbit media enzyme, activity was also observed at neutral pH with another optimum at pH 7. The supernatant enzyme from guinea pig media exhibited only a single pH optimum of 7. Cholesterol ester hydrolase activity from either rabbit or guinea pig media was not influenced by preincubation with cyclic AMP, ATP and protein kinase. The addition of chloroquine resulted in the inhibition of both the rabbit and guinea pig enzyme. Cholesterol ester hydrolase activity from rabbit and guinea pig media was also inhibited by phenyl methane sulfonyl fluoride; activity measured at pH 7 (guinea pig) was more sensitive to inhibition than activity measured at pH 5 (guinea pig and rabbit)."}
{"id": "PMID:30464", "title": "Accuracy of an automated blood-gas analyser operated by untrained staff.", "content": "Performance of the IL 613 automatic blood-gas analyser has been assessed using a group of 100 \"analysts\" with no previous training or experience in the use of the instrument. Test material consisted of blood equilibrated to a known PO2 and PCO2 in a tonometer: pH estimations were carried out on thawed aliquots of a large batch of frozen serum which were then equilibrated to a known PCO2. Eighty-six per cent of analyses were within acceptable limits of error. The largest proportion of errors was in the measurement of pH. Satisfactory results were obtained in 98% of the analyses of PO2 and PCO2. Eighty-eight per cent of operators were able to use the analyser after instruction lasting less than 1 min. These results were significantly better than those obtained in a regional survey of 16 blood-gas laboratories, staffed by trained technicians.", "contents": "Accuracy of an automated blood-gas analyser operated by untrained staff. Performance of the IL 613 automatic blood-gas analyser has been assessed using a group of 100 \"analysts\" with no previous training or experience in the use of the instrument. Test material consisted of blood equilibrated to a known PO2 and PCO2 in a tonometer: pH estimations were carried out on thawed aliquots of a large batch of frozen serum which were then equilibrated to a known PCO2. Eighty-six per cent of analyses were within acceptable limits of error. The largest proportion of errors was in the measurement of pH. Satisfactory results were obtained in 98% of the analyses of PO2 and PCO2. Eighty-eight per cent of operators were able to use the analyser after instruction lasting less than 1 min. These results were significantly better than those obtained in a regional survey of 16 blood-gas laboratories, staffed by trained technicians."}
{"id": "PMID:30465", "title": "Comparative study of two long-acting tranquillizers for oral premedication.", "content": "Lorazepam 2.5 mg was compared with promethazine 50 mg as oral premedication in a double-blind study in women. The premedication was given at the same time to all patients on each operating list, and both drugs continued to be effective 6 h after ingestion. A similar number of patients considered each drug to have relieved anxiety and the amnesic effect of lorazepam was confirmed. However, the use of lorazepam alone was accompanied by significantly more salivation during and after anaesthesia than the use of promethazine, especially in patients in whom the trachea was intubated. There was also a higher frequency of vomiting during and after operation with lorazepam (seven of 67 patients) than after promethazine (one of 71 patients). Promethazine produced dyskinetic side-effects in six of 71 patients.", "contents": "Comparative study of two long-acting tranquillizers for oral premedication. Lorazepam 2.5 mg was compared with promethazine 50 mg as oral premedication in a double-blind study in women. The premedication was given at the same time to all patients on each operating list, and both drugs continued to be effective 6 h after ingestion. A similar number of patients considered each drug to have relieved anxiety and the amnesic effect of lorazepam was confirmed. However, the use of lorazepam alone was accompanied by significantly more salivation during and after anaesthesia than the use of promethazine, especially in patients in whom the trachea was intubated. There was also a higher frequency of vomiting during and after operation with lorazepam (seven of 67 patients) than after promethazine (one of 71 patients). Promethazine produced dyskinetic side-effects in six of 71 patients."}
{"id": "PMID:30467", "title": "A study of naloxone and doxapram as agents for the reversal of neuroleptanalgesic respiratory depression in the conscious rabbit.", "content": "The effectiveness of naloxone and doxapram in reversing the respiratory depressant actions of fentanyl and droperidol in the rabbit has been examined. Both drugs did not reverse fully the depression of respiratory frequency produced by the neuroleptanalgesic agents. Doxapram also failed to reverse fully the depression of minute volume produced by fentanyl and droperidol, although naloxone was adequate in this respect. However, analysis of arterialized venous blood showed that both naloxone and doxapram not only prevented the increase in PCO2 caused by fentanyl and droperidol, but caused also a significant decrease. A reduction in PCO2 was seen also when either naloxone or doxapram was given to untreated rabbits. With doxapram this appeared to be a result of pure respiratory stimulation. Naloxone also produced a reduction in standard bicarbonate.", "contents": "A study of naloxone and doxapram as agents for the reversal of neuroleptanalgesic respiratory depression in the conscious rabbit. The effectiveness of naloxone and doxapram in reversing the respiratory depressant actions of fentanyl and droperidol in the rabbit has been examined. Both drugs did not reverse fully the depression of respiratory frequency produced by the neuroleptanalgesic agents. Doxapram also failed to reverse fully the depression of minute volume produced by fentanyl and droperidol, although naloxone was adequate in this respect. However, analysis of arterialized venous blood showed that both naloxone and doxapram not only prevented the increase in PCO2 caused by fentanyl and droperidol, but caused also a significant decrease. A reduction in PCO2 was seen also when either naloxone or doxapram was given to untreated rabbits. With doxapram this appeared to be a result of pure respiratory stimulation. Naloxone also produced a reduction in standard bicarbonate."}
{"id": "PMID:30469", "title": "Collection, cryopreservation and subsequent viability of haemopoietic stem cells intended for treatment of chronic granulocytic leukaemia in blast-cell transformation.", "content": "We have stored at -196 degrees C peripheral blood buffy coat (BC) and bone marrow (BM) cells collected from 47 patients with chronic granulocytic leukaemia in the chronic phase. Dimethyl sulphoxide (DMSO) 10% was used as cryoprotective agent. As these cells include CFUc and probably pluripotential stem cells they may be transfused as part of the management of patients who enter blast cell transformation. The mean numbers of nucleated cells collected and stored per procedure was about 9 times greater for BC collections than for BM harvests (106 +/- 49 (SD) X 10(9) versus 11.9 +/- 6.6 X 10(9) respectively). Agar CFUc assay showed that stored cells may remain viable for up to 5 years. Since in vitro studies showed that CFUc proliferation is not inhibited by low concentrations of DMSO the removal of all DMSO during cell reconstitution before transfusion may not be necessary. If autologous BC cells are capable of repopulating the BM of patients treated for CGL in blast cell transformation the routine collection and storage of BC rather than BM cells may be desirable for all newly diagnosed patients.", "contents": "Collection, cryopreservation and subsequent viability of haemopoietic stem cells intended for treatment of chronic granulocytic leukaemia in blast-cell transformation. We have stored at -196 degrees C peripheral blood buffy coat (BC) and bone marrow (BM) cells collected from 47 patients with chronic granulocytic leukaemia in the chronic phase. Dimethyl sulphoxide (DMSO) 10% was used as cryoprotective agent. As these cells include CFUc and probably pluripotential stem cells they may be transfused as part of the management of patients who enter blast cell transformation. The mean numbers of nucleated cells collected and stored per procedure was about 9 times greater for BC collections than for BM harvests (106 +/- 49 (SD) X 10(9) versus 11.9 +/- 6.6 X 10(9) respectively). Agar CFUc assay showed that stored cells may remain viable for up to 5 years. Since in vitro studies showed that CFUc proliferation is not inhibited by low concentrations of DMSO the removal of all DMSO during cell reconstitution before transfusion may not be necessary. If autologous BC cells are capable of repopulating the BM of patients treated for CGL in blast cell transformation the routine collection and storage of BC rather than BM cells may be desirable for all newly diagnosed patients."}
{"id": "PMID:30470", "title": "Continuous fetal tissue pH recordings during labour. A preliminary report.", "content": "We made continuous fetal pH-measurement in 50 patients and showed a good correlation between tissue pH and umbilical artery, umbilical vein and the fetal scalp blood pH. There were practical problems in the use of the glass pH electrode.", "contents": "Continuous fetal tissue pH recordings during labour. A preliminary report. We made continuous fetal pH-measurement in 50 patients and showed a good correlation between tissue pH and umbilical artery, umbilical vein and the fetal scalp blood pH. There were practical problems in the use of the glass pH electrode."}
{"id": "PMID:30471", "title": "Low pH dimerization of chymotrypsin in solution.", "content": "The mechanism of the acid dimerization of alpha-chymotrypsin in solution was reexamined using a number of chemical derivatives. Blocking of the carboxyl of Tyr-146, while that of ASP-64 remained free, eliminated completely the ability of alpha-chymotrypsin to dimerize, as did methylation of His-57. O-Acetylation of Tyr-146 reduced the dimerization constant to that of gamma-chymotrypsin, and deacetylation of the other accessible tyrosines did not affect the dimerization. It is concluded that the mechanism proposed by Aune and Timasheff [Aune, K.C., and Timasheff, S.N.(1971) Biochemistry 10, 1609-1617] for the solution dimerization which involves the electrostatic interaction between the His-57 imidazolium ring and the terminal carboxyl of Tyr-146 is still most consistent with all the experimental observations. The interactions in dilute solution may differ somewhat from those observed in crystals. In particular, the two intermolecular bridges formed by sulfate ions in crystals cannot be present in solution.", "contents": "Low pH dimerization of chymotrypsin in solution. The mechanism of the acid dimerization of alpha-chymotrypsin in solution was reexamined using a number of chemical derivatives. Blocking of the carboxyl of Tyr-146, while that of ASP-64 remained free, eliminated completely the ability of alpha-chymotrypsin to dimerize, as did methylation of His-57. O-Acetylation of Tyr-146 reduced the dimerization constant to that of gamma-chymotrypsin, and deacetylation of the other accessible tyrosines did not affect the dimerization. It is concluded that the mechanism proposed by Aune and Timasheff [Aune, K.C., and Timasheff, S.N.(1971) Biochemistry 10, 1609-1617] for the solution dimerization which involves the electrostatic interaction between the His-57 imidazolium ring and the terminal carboxyl of Tyr-146 is still most consistent with all the experimental observations. The interactions in dilute solution may differ somewhat from those observed in crystals. In particular, the two intermolecular bridges formed by sulfate ions in crystals cannot be present in solution."}
{"id": "PMID:30475", "title": "Phosphorus-31 nuclear magnetic resonance studies of active proton translocation in chromaffin granules.", "content": "ATP hydrolysis and proton translocation in chromaffin granules were followed using 31P nuclear magnetic resonance. The intragranular pH affects the resonance frequency of the gamma-phosphate of granular ATP. By measuring frequency vs. pH in solutions which simulate the intragranular matrix, this may be calibrated to give quantitative pH measurements. The pH in the resting granule is 5.65 +/- 0.15. This drops by 0.4 to 0.5 pH unit when ATP is added externally and protons are actively pumped into the granules. Because of differences in the composition and pH of the internal and external solutions, the resonances of internal and external nucleotides and Pi can be distinguished. Consequently, ATP hydrolysis and changes in internal pH may be observed simultaneously and continuously in a single sample of chromaffin granules. From the measured buffering capacity of a reconstituted intragranular solution, pH changes were converted into an absolute number of protons translocated. The net proton flux (protons translocated/ATP hydrolyzed) was about 1.0 immediately after external ATP addition but fell toward zero as the pH gradient increased to a new steady state. These 31P NMR results agree with intragranular pH measurements determined from methylamine distribution and with H+/ATP stoichiometries calculated from pH changes observed in the external medium.", "contents": "Phosphorus-31 nuclear magnetic resonance studies of active proton translocation in chromaffin granules. ATP hydrolysis and proton translocation in chromaffin granules were followed using 31P nuclear magnetic resonance. The intragranular pH affects the resonance frequency of the gamma-phosphate of granular ATP. By measuring frequency vs. pH in solutions which simulate the intragranular matrix, this may be calibrated to give quantitative pH measurements. The pH in the resting granule is 5.65 +/- 0.15. This drops by 0.4 to 0.5 pH unit when ATP is added externally and protons are actively pumped into the granules. Because of differences in the composition and pH of the internal and external solutions, the resonances of internal and external nucleotides and Pi can be distinguished. Consequently, ATP hydrolysis and changes in internal pH may be observed simultaneously and continuously in a single sample of chromaffin granules. From the measured buffering capacity of a reconstituted intragranular solution, pH changes were converted into an absolute number of protons translocated. The net proton flux (protons translocated/ATP hydrolyzed) was about 1.0 immediately after external ATP addition but fell toward zero as the pH gradient increased to a new steady state. These 31P NMR results agree with intragranular pH measurements determined from methylamine distribution and with H+/ATP stoichiometries calculated from pH changes observed in the external medium."}
{"id": "PMID:30476", "title": "Synthesis and hydrolysis of ATP by intact chloroplasts under flash illumination and in darkness.", "content": "ATP concentrations were measured in isolated intact spinach chloroplasts under various light and dark conditions. The following results were obtained: (1) Even in darkened chloroplasts and in the absence of exogenous substrates, ATP levels in the chloroplast stroma were significant. They decreased on addition of glycerate, phosphoglycerate or dihydroxyacetone phosphate. When dihydroxyacetone phosphate and oxaloacetate were added together, ATP levels increased in darkened chloroplasts owing to substrate level phosphorylation. (2) Under illumination with saturating single turnover flashes, oxygen evolution in the presence of phosphoglycerate, whose reduction requires ATP, was no lower on a unit flash basis at the low flash frequency of 2 Hz than at higher frequencies. Quenching of 9-aminoacridine fluorescence, which indicates the formation of a proton gradient in intact chloroplasts, decreased with decreasing flash frequencies, until there was no significant fluorescence quenching at a flash frequency of about 2 Hz. In contrast to intact chloroplasts, broken chloroplasts did not phosphorylate much ADP at the low flash frequency of 2 Hz. (3) Flashing at extremely low frequencies (0.2 Hz) caused ATP hydrolysis rather than ATP synthesis in intact chloroplasts. At higher flash frequencies, synthesis replaced hydrolysis. Still, even at high frequencies (10 Hz), the first flashes of a series of flashes given after a long dark time always decreased chloroplast ATP levels. From these results, it is concluded that the enzyme, which mediates ATP synthesis in the light, is inactive in darkened intact chloroplasts. Its light activation can be separated from the formation of the high energy condition, which results in ATP synthesis. After its activation, the enzyme catalyzes a reversible reaction.", "contents": "Synthesis and hydrolysis of ATP by intact chloroplasts under flash illumination and in darkness. ATP concentrations were measured in isolated intact spinach chloroplasts under various light and dark conditions. The following results were obtained: (1) Even in darkened chloroplasts and in the absence of exogenous substrates, ATP levels in the chloroplast stroma were significant. They decreased on addition of glycerate, phosphoglycerate or dihydroxyacetone phosphate. When dihydroxyacetone phosphate and oxaloacetate were added together, ATP levels increased in darkened chloroplasts owing to substrate level phosphorylation. (2) Under illumination with saturating single turnover flashes, oxygen evolution in the presence of phosphoglycerate, whose reduction requires ATP, was no lower on a unit flash basis at the low flash frequency of 2 Hz than at higher frequencies. Quenching of 9-aminoacridine fluorescence, which indicates the formation of a proton gradient in intact chloroplasts, decreased with decreasing flash frequencies, until there was no significant fluorescence quenching at a flash frequency of about 2 Hz. In contrast to intact chloroplasts, broken chloroplasts did not phosphorylate much ADP at the low flash frequency of 2 Hz. (3) Flashing at extremely low frequencies (0.2 Hz) caused ATP hydrolysis rather than ATP synthesis in intact chloroplasts. At higher flash frequencies, synthesis replaced hydrolysis. Still, even at high frequencies (10 Hz), the first flashes of a series of flashes given after a long dark time always decreased chloroplast ATP levels. From these results, it is concluded that the enzyme, which mediates ATP synthesis in the light, is inactive in darkened intact chloroplasts. Its light activation can be separated from the formation of the high energy condition, which results in ATP synthesis. After its activation, the enzyme catalyzes a reversible reaction."}
{"id": "PMID:30477", "title": "Responses of the a3 component of cytochrome c oxidase to substrate and ligand addition.", "content": "We have previously described a transient high spin ferric heme species in cytochrome c oxidase (EC 1.9.3.1) which represent a3+(3) (Beinert, H. and Shaw, R.W.(1977) Biochim. Biophys. Acta 462, 12u--130), and can be detected and quantitatively determined by EPR. We have now used out ability to generate this species to study reactions of a3+(3) with substrates and ligands and also responses to pH changes. This was accomplished by multiple rapid mixing and freezing techniques in conjunction with low temperature EPR and optical reflectance spectroscopies. The substrates used were O2 and ferrocytochrome c and the ligands cyanide, sulfide, azide and carbon monoxide. Contrary to the oxidized, resting form of the enzyme, the transient high spin species of a3+(3) reacts within less than 10 ms stoichiometrically with cyanide and sulfide and at a slower rate with azide. The transient a3+(3) species responds to O2 and CO by changes in signal size or shape, although no oxidoreduction is involved, indicating that a3+(3) registers the presence of these gases. The high spin signal of the transient species is readily abolished by ferrocytochrome c or on raising the pH. Decreasing the pH induces a shift from the rhombic towards the axial component of the signal. Since the responses to CO and pH are analogous for the rhombic transient species to those observed with the rhombic high spin ferric heme species produced on partial reduction, it is suggested that the rhombic signals represent a3+(3) in either case. In all these experiments, in which EPR detectable a3+(3) was observed in large yield, no extra signals for copper or correspondingly increased intensity in the copper signal at g = 2 were seen. The relationship is discussed of the obviously reactive transient species of a3+(3) to other 'activated' species that have been reported and to the oxidized resting form of the enzyme, which is known to react only slowly with ligands and to respond sluggishly to substrate.", "contents": "Responses of the a3 component of cytochrome c oxidase to substrate and ligand addition. We have previously described a transient high spin ferric heme species in cytochrome c oxidase (EC 1.9.3.1) which represent a3+(3) (Beinert, H. and Shaw, R.W.(1977) Biochim. Biophys. Acta 462, 12u--130), and can be detected and quantitatively determined by EPR. We have now used out ability to generate this species to study reactions of a3+(3) with substrates and ligands and also responses to pH changes. This was accomplished by multiple rapid mixing and freezing techniques in conjunction with low temperature EPR and optical reflectance spectroscopies. The substrates used were O2 and ferrocytochrome c and the ligands cyanide, sulfide, azide and carbon monoxide. Contrary to the oxidized, resting form of the enzyme, the transient high spin species of a3+(3) reacts within less than 10 ms stoichiometrically with cyanide and sulfide and at a slower rate with azide. The transient a3+(3) species responds to O2 and CO by changes in signal size or shape, although no oxidoreduction is involved, indicating that a3+(3) registers the presence of these gases. The high spin signal of the transient species is readily abolished by ferrocytochrome c or on raising the pH. Decreasing the pH induces a shift from the rhombic towards the axial component of the signal. Since the responses to CO and pH are analogous for the rhombic transient species to those observed with the rhombic high spin ferric heme species produced on partial reduction, it is suggested that the rhombic signals represent a3+(3) in either case. In all these experiments, in which EPR detectable a3+(3) was observed in large yield, no extra signals for copper or correspondingly increased intensity in the copper signal at g = 2 were seen. The relationship is discussed of the obviously reactive transient species of a3+(3) to other 'activated' species that have been reported and to the oxidized resting form of the enzyme, which is known to react only slowly with ligands and to respond sluggishly to substrate."}
{"id": "PMID:30478", "title": "Proton-translocating cytochrome c oxidase in artificial phospholipid vesicles.", "content": "The proton translocating properties of cytochrome c oxidase have been studied in artificial phospholipid vesicles into the membranes of which the isolated and purified enzyme was incorporated. Initiation of oxidation of ferrocytochrome c by addition of the cytochrome, or by addition of oxygen to an anaerobic vesicle suspension, leads to ejection of H+ from the vesicles provided that charge compensation is permitted by the presence of valinomycin and K+. Proton ejection is not observed if the membranes have been specifically rendered permeable to protons. The proton ejection is the result of true translocation of H+ across the membrane as indicated by its dependence on the intravesicular buffering power relative to the number of particles (electrons and protons) transferred by the system, and since it can be shown not to be due to a net formation of acid in the system. Comparison of the initial rates of proton ejection and oxidation of cytochrome c yields a H+/e- quotient close to 1.0 both in cytochrome c and oxygen pulse experiments. An approach towards the same stoichiometry is found by comparison of the extents of proton ejection and electron transfer under appropriate experimental conditions. It is concluded that cytochrome c oxidase is a proton pump, which conserves redox energy by converting it into an electrochemical proton gradient through electrogenic translocation of H+.", "contents": "Proton-translocating cytochrome c oxidase in artificial phospholipid vesicles. The proton translocating properties of cytochrome c oxidase have been studied in artificial phospholipid vesicles into the membranes of which the isolated and purified enzyme was incorporated. Initiation of oxidation of ferrocytochrome c by addition of the cytochrome, or by addition of oxygen to an anaerobic vesicle suspension, leads to ejection of H+ from the vesicles provided that charge compensation is permitted by the presence of valinomycin and K+. Proton ejection is not observed if the membranes have been specifically rendered permeable to protons. The proton ejection is the result of true translocation of H+ across the membrane as indicated by its dependence on the intravesicular buffering power relative to the number of particles (electrons and protons) transferred by the system, and since it can be shown not to be due to a net formation of acid in the system. Comparison of the initial rates of proton ejection and oxidation of cytochrome c yields a H+/e- quotient close to 1.0 both in cytochrome c and oxygen pulse experiments. An approach towards the same stoichiometry is found by comparison of the extents of proton ejection and electron transfer under appropriate experimental conditions. It is concluded that cytochrome c oxidase is a proton pump, which conserves redox energy by converting it into an electrochemical proton gradient through electrogenic translocation of H+."}
{"id": "PMID:30479", "title": "Surface charges on chloroplast membranes as studied by particle electrophoresis.", "content": "1. Particle microelectrophoresis mobility studies have been conducted with chloroplast thylakoid membranes and with isolated intact chloroplasts. 2. The pH dependence of the electrophoretic mobility indicated that at pH values above 4.3 both membrane systems carry a net negative charge. 3. Chemical treatment of thylakoids has shown that neither the sugar residues of the galactolipids in the membrane nor the basic groups of the membrane proteins having pK values between 6 and 10 are exposed at the surface. 4. However, treatment with 1-ethyl-3(3-dimethylaminopropyl)carbodiimide, together with glycine methyl ester, neutralized the negative charges on the thylakoid membrane surface indicating the involvement of carboxyl groups which, because of their pH sensitivity, are likely to be the carboxyl groups of aspartic and glutamic acid residues. 5. The nature of the protein giving rise to the negative surface charges on the thylakoids is not known but is shown not to involve the coupling factor or the light harvesting chlorophyll a/chlorophyll b pigment . protein complex. 6. No significant effect of light was observed on the electrophoretic mobility of either thylakoids or intact chloroplasts. 7. The striking difference in the ability of divalent and monovalent cations to screen the surface charges was demonstrated and explained in terms of the Gouy-Chapman theory. 8. Calculations of the zeta-potentials for thylakoid membranes gave values for the charge density at the plane of shear to be in the region of one electronic charge per 1500--2000 A2. 9. The significance of the results is discussed in terms of cation distribution in chloroplasts and the effect of cations on photosynthetic phenomena.", "contents": "Surface charges on chloroplast membranes as studied by particle electrophoresis. 1. Particle microelectrophoresis mobility studies have been conducted with chloroplast thylakoid membranes and with isolated intact chloroplasts. 2. The pH dependence of the electrophoretic mobility indicated that at pH values above 4.3 both membrane systems carry a net negative charge. 3. Chemical treatment of thylakoids has shown that neither the sugar residues of the galactolipids in the membrane nor the basic groups of the membrane proteins having pK values between 6 and 10 are exposed at the surface. 4. However, treatment with 1-ethyl-3(3-dimethylaminopropyl)carbodiimide, together with glycine methyl ester, neutralized the negative charges on the thylakoid membrane surface indicating the involvement of carboxyl groups which, because of their pH sensitivity, are likely to be the carboxyl groups of aspartic and glutamic acid residues. 5. The nature of the protein giving rise to the negative surface charges on the thylakoids is not known but is shown not to involve the coupling factor or the light harvesting chlorophyll a/chlorophyll b pigment . protein complex. 6. No significant effect of light was observed on the electrophoretic mobility of either thylakoids or intact chloroplasts. 7. The striking difference in the ability of divalent and monovalent cations to screen the surface charges was demonstrated and explained in terms of the Gouy-Chapman theory. 8. Calculations of the zeta-potentials for thylakoid membranes gave values for the charge density at the plane of shear to be in the region of one electronic charge per 1500--2000 A2. 9. The significance of the results is discussed in terms of cation distribution in chloroplasts and the effect of cations on photosynthetic phenomena."}
{"id": "PMID:30480", "title": "Control of the Ca2+-triggered bioluminescence of Veretillum cynomorium lumisomes.", "content": "Calcium ions can trigger an emission of light from Veretillum cynomorium lumisomes (bioluminescent vesicles) under conditions where they are not lysed. This process does not require a metabolically-linked source of energy, but is dependent upon the nature of the ions present inside and outside the vesicles. The Ca2+-triggered bioluminescence is stimulated by an asymmetrical distribution of cations or anions. Either high internal sodium or high external chloride is required for the maximal effect. When sodium is present outside the structure and potassium inside, the slow inward diffusion of calcium is decreased. Unbalanced diffusion of internal cations also stimulates the bioluminescence, suggesting control of the calcium influx by an electrochemical gradient. It is assumed that rapid outward diffusion of sodium or inward diffusion of chloride generates an electrical potential difference (inside negative) which drives the Ca2+-influx. With purified lumisomes it has been shown that Ca2+-triggered bioluminescence and calcium uptake (presumably net uptake) were correlated. In two instances uptake of the lipophilic cation dibenzyldimethylammonium has given direct evidence for the existence of a potential difference. With NaCl-loaded vesicles, it has not been possible to demonstrate an uptake of lipophilic cations but experiments with 22Na and 42D indicated a higher rate of sodium efflux, in accord with the proposed hypothesis.", "contents": "Control of the Ca2+-triggered bioluminescence of Veretillum cynomorium lumisomes. Calcium ions can trigger an emission of light from Veretillum cynomorium lumisomes (bioluminescent vesicles) under conditions where they are not lysed. This process does not require a metabolically-linked source of energy, but is dependent upon the nature of the ions present inside and outside the vesicles. The Ca2+-triggered bioluminescence is stimulated by an asymmetrical distribution of cations or anions. Either high internal sodium or high external chloride is required for the maximal effect. When sodium is present outside the structure and potassium inside, the slow inward diffusion of calcium is decreased. Unbalanced diffusion of internal cations also stimulates the bioluminescence, suggesting control of the calcium influx by an electrochemical gradient. It is assumed that rapid outward diffusion of sodium or inward diffusion of chloride generates an electrical potential difference (inside negative) which drives the Ca2+-influx. With purified lumisomes it has been shown that Ca2+-triggered bioluminescence and calcium uptake (presumably net uptake) were correlated. In two instances uptake of the lipophilic cation dibenzyldimethylammonium has given direct evidence for the existence of a potential difference. With NaCl-loaded vesicles, it has not been possible to demonstrate an uptake of lipophilic cations but experiments with 22Na and 42D indicated a higher rate of sodium efflux, in accord with the proposed hypothesis."}
{"id": "PMID:30481", "title": "Role of beta-carotene in the reaction centres of photosystems I and II of spinach chloroplasts prepared in non-polar solvents.", "content": "Spinach chloroplasts have been prepared nonaqueously using non-polar solvents (n-hexane, CCl4, n-hepatane) and the beta-carotene content extracted in a controlled manner. This procedure is reproducible and does not result in large structural or spectral changes of the chloroplasts. The organisation of the chlorophyll-proteins is unaltered, as fragmentation with digitonin results in the appearance of the same fractions as found previously for aqueously-prepared chloroplasts, including the pink zone containing cytochromes f and b6 in the ratio 1 : 2. The chloroplasts possess both Photosystem I activity (P-700 photo-bleaching, and NADP+ photoreduction) and Photosystem II activity (parabenzoquinone reduction with Mn2+ as electron donor, and chlorophyll fluorescence induction). Use of moderate intensity red illumination has allowed a study of the role of beta-carotene in photochemistry separate from its roles in energy transfer and photoprotection. Removal of the fraction of beta-carotene closely associated with the Photosystem I reaction centre caused the rate of NADP+ photoreduction to fall to a low, but significantly non-zero level. Thus, in the complete absence of beta-carotene, photochemistry can still be observed, however the specific association of beta-carotene with the reaction centre is required for maximal rates. We propose that beta-carotene bound at the reaction centre decreases the rate of transfer of excitation energy away from the reaction centre, and increases the rate of photochemistry. It is possible that this occurs via formation of an exciplex between ground state beta-carotene and chlorophyll in the first excited state.", "contents": "Role of beta-carotene in the reaction centres of photosystems I and II of spinach chloroplasts prepared in non-polar solvents. Spinach chloroplasts have been prepared nonaqueously using non-polar solvents (n-hexane, CCl4, n-hepatane) and the beta-carotene content extracted in a controlled manner. This procedure is reproducible and does not result in large structural or spectral changes of the chloroplasts. The organisation of the chlorophyll-proteins is unaltered, as fragmentation with digitonin results in the appearance of the same fractions as found previously for aqueously-prepared chloroplasts, including the pink zone containing cytochromes f and b6 in the ratio 1 : 2. The chloroplasts possess both Photosystem I activity (P-700 photo-bleaching, and NADP+ photoreduction) and Photosystem II activity (parabenzoquinone reduction with Mn2+ as electron donor, and chlorophyll fluorescence induction). Use of moderate intensity red illumination has allowed a study of the role of beta-carotene in photochemistry separate from its roles in energy transfer and photoprotection. Removal of the fraction of beta-carotene closely associated with the Photosystem I reaction centre caused the rate of NADP+ photoreduction to fall to a low, but significantly non-zero level. Thus, in the complete absence of beta-carotene, photochemistry can still be observed, however the specific association of beta-carotene with the reaction centre is required for maximal rates. We propose that beta-carotene bound at the reaction centre decreases the rate of transfer of excitation energy away from the reaction centre, and increases the rate of photochemistry. It is possible that this occurs via formation of an exciplex between ground state beta-carotene and chlorophyll in the first excited state."}
{"id": "PMID:30483", "title": "Erythrocyte membrane potentials determined by hydrogen ion distribution.", "content": "If the extracellular fluid is left unbuffered, dynamic membrane potential changes in the red blood cell may be determined from external pH readings. For some types of experiments it is necessary to accelerate H+ equilibration by adding minute amounts of hydrogen carriers. The method is independent of hematocrit over a wide range of membrane potential changes. Membrane potential jumps produced by permeability changes or by changes in ionic composition may be measured. The method provides a convenient means of measuring parameters of both the conductive and non-conductive anion pathways in the red cell.", "contents": "Erythrocyte membrane potentials determined by hydrogen ion distribution. If the extracellular fluid is left unbuffered, dynamic membrane potential changes in the red blood cell may be determined from external pH readings. For some types of experiments it is necessary to accelerate H+ equilibration by adding minute amounts of hydrogen carriers. The method is independent of hematocrit over a wide range of membrane potential changes. Membrane potential jumps produced by permeability changes or by changes in ionic composition may be measured. The method provides a convenient means of measuring parameters of both the conductive and non-conductive anion pathways in the red cell."}
{"id": "PMID:30484", "title": "The hyperpolarizing and depolarizing effects of 2,4-dinitrophenol on Ehrlich cells.", "content": "The ability of glucose to reverse the effects of dinitrophenol on amino acid uptake in Ehrlich cells is a function of pH. At pH 6.0, the presence of glucose does not reverse the inhibitory action of the uncoupler. Nearly complete restoration occurs with glucose at pH 7.4. At pH 8, the presence of glucose may cause a modest increase in amino acid uptake in presence of dinitrophenol. At all pH values, glucose restores ATP and cellular K+ to the control levels at the same pH. Although the cytoplasmic pH changes with changes in the external pH, the cell interior is more alkaline than the medium near pH 6.0 and more acid than the medium at pH 7.8 even after 45 min incubation at 37 degrees C. With dinitrophenol and in presence of glucose the difference in pH between the medium and the cell is minimal at both pH 6.0 and 7.8.", "contents": "The hyperpolarizing and depolarizing effects of 2,4-dinitrophenol on Ehrlich cells. The ability of glucose to reverse the effects of dinitrophenol on amino acid uptake in Ehrlich cells is a function of pH. At pH 6.0, the presence of glucose does not reverse the inhibitory action of the uncoupler. Nearly complete restoration occurs with glucose at pH 7.4. At pH 8, the presence of glucose may cause a modest increase in amino acid uptake in presence of dinitrophenol. At all pH values, glucose restores ATP and cellular K+ to the control levels at the same pH. Although the cytoplasmic pH changes with changes in the external pH, the cell interior is more alkaline than the medium near pH 6.0 and more acid than the medium at pH 7.8 even after 45 min incubation at 37 degrees C. With dinitrophenol and in presence of glucose the difference in pH between the medium and the cell is minimal at both pH 6.0 and 7.8."}
{"id": "PMID:30485", "title": "The effect of bovine serum albumin on partial reactions of palmitoyl-CoA chain elongation by rat liver microsomes.", "content": "In the absence of albumin, v/s curves for both condensation and overall chain elongation demonstrated that the specific activity for overall chain elongation was 3.7 times that of condensation. When the molar ratio of palmitoyl-CoA to albumin was greater than 2 : 1, the specific activity of chain elongation exceeded that of condensation. At these low albumin concentrations, in the absence of NADPH, the beta-ketostearoyl-coA was converted back to palmitate. This cleavage reaction is inhibited by albumin in a concentration-dependent manner. When the palmitoyl-CoA to albumin molar ratio was less than 2 : 1, the specific activity for condensation exceeded that for overall chain elongation and some beta-ketostearate was shown to accumulate under chain elongation conditions. The specific activity for dehydration of beta-hydroxystearoyl-CoA was maximal when the acyl-CoA to albumin molar ratio was between 10 : 1 and 4 : 1 but the rate of this reaction was not markedly influenced by variations in albumin concentration. The specific activity for the NADPH-dependent reduction of 2-trans-octa-decenoyl-CoA was 18 nmol . min(-1) . mg(-1) in the absence of albumin and increased to a maximum of 112 when the substrate to albumin molar ratio was 2 : 1. At higher albumin concentrations the reductase reaction was inhibited. Conversely, the specific activity for the reverse dehydrase was maximal at low albumin concentrations and the rate of this reaction declined as the albumin concentration increased. Our results demonstrate that albumin not only alleviates a substrate induced inhibition but also regulates the metabolic fate of 2-trans-octadecenoyl-CoA and in this regard may possibly substitute for acyl-CoA binding proteins.", "contents": "The effect of bovine serum albumin on partial reactions of palmitoyl-CoA chain elongation by rat liver microsomes. In the absence of albumin, v/s curves for both condensation and overall chain elongation demonstrated that the specific activity for overall chain elongation was 3.7 times that of condensation. When the molar ratio of palmitoyl-CoA to albumin was greater than 2 : 1, the specific activity of chain elongation exceeded that of condensation. At these low albumin concentrations, in the absence of NADPH, the beta-ketostearoyl-coA was converted back to palmitate. This cleavage reaction is inhibited by albumin in a concentration-dependent manner. When the palmitoyl-CoA to albumin molar ratio was less than 2 : 1, the specific activity for condensation exceeded that for overall chain elongation and some beta-ketostearate was shown to accumulate under chain elongation conditions. The specific activity for dehydration of beta-hydroxystearoyl-CoA was maximal when the acyl-CoA to albumin molar ratio was between 10 : 1 and 4 : 1 but the rate of this reaction was not markedly influenced by variations in albumin concentration. The specific activity for the NADPH-dependent reduction of 2-trans-octa-decenoyl-CoA was 18 nmol . min(-1) . mg(-1) in the absence of albumin and increased to a maximum of 112 when the substrate to albumin molar ratio was 2 : 1. At higher albumin concentrations the reductase reaction was inhibited. Conversely, the specific activity for the reverse dehydrase was maximal at low albumin concentrations and the rate of this reaction declined as the albumin concentration increased. Our results demonstrate that albumin not only alleviates a substrate induced inhibition but also regulates the metabolic fate of 2-trans-octadecenoyl-CoA and in this regard may possibly substitute for acyl-CoA binding proteins."}
{"id": "PMID:30486", "title": "Parvalbumins from coelacanth muscle. II. Amino acid sequence of the two less acidic components.", "content": "The primary structure of the two less acidic parvalbumins (pI = 5.44 and pI = 4.95) from coelacanth muscle (Latimeria chalumnae) has been determined. They differ only by the presence or absence of a N-terminal blocking group. By the use of the automatic degradation, 69 amino acids could be placed unambiguously in the N-terminal part and 24 amino acids following the single arginine 75. Tryptic peptides were used to establish the sequence and the position of the remaining residues. The two parvalbumins examined belong to the alpha-lineage, and the rate of their molecular evolution is comparable to that found in other vertebrates.", "contents": "Parvalbumins from coelacanth muscle. II. Amino acid sequence of the two less acidic components. The primary structure of the two less acidic parvalbumins (pI = 5.44 and pI = 4.95) from coelacanth muscle (Latimeria chalumnae) has been determined. They differ only by the presence or absence of a N-terminal blocking group. By the use of the automatic degradation, 69 amino acids could be placed unambiguously in the N-terminal part and 24 amino acids following the single arginine 75. Tryptic peptides were used to establish the sequence and the position of the remaining residues. The two parvalbumins examined belong to the alpha-lineage, and the rate of their molecular evolution is comparable to that found in other vertebrates."}
{"id": "PMID:30487", "title": "The involvement of one of the three histidine residues of cow kappa-casein in the chymosin-initiated milk clotting process.", "content": "Cow kappa-casein has been modified by photo-oxidation in the presence of rose bengal and by the chemical reagents diethyl pyrocarbonate, 2-hydroxy-5-nitro-benzyl bromide and iodoacetic acid. Photo-oxidation resulted in the destruction of histidine and tryptophan residues and all of the histidines could be ethoxy-formylated by treatment with diethyl pyrocarbonate. Both procedures caused a loss in the susceptibility of the Phe-Met linkage of kappa-casein to chymosin hydrolysis. Treatment of kappa-casein with 2-hydroxy-5-nitrobenzyl bromide and iodoacetic acid caused the loss of tryptophan and methionine residues respectively but, in both cases, the susceptibility of the modified protein to chymosin hydrolysis remained unaffected. Of the amino acids examined it is concluded that only the histidine residues of cow kappa-casein are important for the hydrolytic action of chymosin and, furthermore, the treatment with diethyl pyrocarbonate suggests that only one of the three histidines plays an essential role.", "contents": "The involvement of one of the three histidine residues of cow kappa-casein in the chymosin-initiated milk clotting process. Cow kappa-casein has been modified by photo-oxidation in the presence of rose bengal and by the chemical reagents diethyl pyrocarbonate, 2-hydroxy-5-nitro-benzyl bromide and iodoacetic acid. Photo-oxidation resulted in the destruction of histidine and tryptophan residues and all of the histidines could be ethoxy-formylated by treatment with diethyl pyrocarbonate. Both procedures caused a loss in the susceptibility of the Phe-Met linkage of kappa-casein to chymosin hydrolysis. Treatment of kappa-casein with 2-hydroxy-5-nitrobenzyl bromide and iodoacetic acid caused the loss of tryptophan and methionine residues respectively but, in both cases, the susceptibility of the modified protein to chymosin hydrolysis remained unaffected. Of the amino acids examined it is concluded that only the histidine residues of cow kappa-casein are important for the hydrolytic action of chymosin and, furthermore, the treatment with diethyl pyrocarbonate suggests that only one of the three histidines plays an essential role."}
{"id": "PMID:30488", "title": "Structural interpretation of lanthanide binding to the basic pancreatic trypsin inhibitor by 1H NMR at 360 MHz.", "content": "The weak binding of lanthanides to the five carboxyl groups of the basic pancreatic trypsin inhibitor (hereafter termed \"the inhibitor\"), has been investigated in detail using high resolution 1H NMR at 360 MHz. Lanthanides bind to the C-terminus with an apparent binding constant of 30 M-1, and thus competitively inhibit the formation of a salt-bridge between the C-terminus and the N-terminus, Lanthanides bind also to the side chain carboxyl groups of Asp 3, Glu 7, Glu 49 and Asp 50, with binding constants of 10--30 M-1. With the use of lanthanides individual resonance assignments for Phe 4 and Phe 45 were obtained in the 1H NMR spectrum of the inhibitor, and for several spin systems previous  identifications were independently confirmed. The present experiments also provide a nice illustration for the use of shift reagents to improve the resolution in 1H NMR spectra of proteins. The exchange broadening for Tyr 35 and Phe 45 over the temperature range 4--72 degrees C could thus be observed for almost all the components of these aromatic spin systems and new details on the dynamic properties were obtained also for other aromatic residues.", "contents": "Structural interpretation of lanthanide binding to the basic pancreatic trypsin inhibitor by 1H NMR at 360 MHz. The weak binding of lanthanides to the five carboxyl groups of the basic pancreatic trypsin inhibitor (hereafter termed \"the inhibitor\"), has been investigated in detail using high resolution 1H NMR at 360 MHz. Lanthanides bind to the C-terminus with an apparent binding constant of 30 M-1, and thus competitively inhibit the formation of a salt-bridge between the C-terminus and the N-terminus, Lanthanides bind also to the side chain carboxyl groups of Asp 3, Glu 7, Glu 49 and Asp 50, with binding constants of 10--30 M-1. With the use of lanthanides individual resonance assignments for Phe 4 and Phe 45 were obtained in the 1H NMR spectrum of the inhibitor, and for several spin systems previous  identifications were independently confirmed. The present experiments also provide a nice illustration for the use of shift reagents to improve the resolution in 1H NMR spectra of proteins. The exchange broadening for Tyr 35 and Phe 45 over the temperature range 4--72 degrees C could thus be observed for almost all the components of these aromatic spin systems and new details on the dynamic properties were obtained also for other aromatic residues."}
{"id": "PMID:30489", "title": "The effect of acid pH and citrate on the release and exchange of iron on rat transferrin.", "content": "The effect of acid pH and citrate on the exchange of iron between binding sites of rat transferrin has been studied. In the absence of citrate, diferric transferrin shows stepwise loss of iron atoms with the first atom of iron released at approximately pH 5.2. Citrate at physiologic concentrations (1.10(-3) M) or greater allows random iron removal at pH 6.5 or less. Iron dissociation from monoferric transferrin at acid pH, with or without citrate, is a random process. At pH 7.4, randomization of iron on transferrin takes from 3 to 6 h in the presence of millimolar concentrations of citrate. We conclude that at acid pH and in the presence of citrate concentrations likely to occur in vivo in the rat there is little scrambling of iron bound to transferrin.", "contents": "The effect of acid pH and citrate on the release and exchange of iron on rat transferrin. The effect of acid pH and citrate on the exchange of iron between binding sites of rat transferrin has been studied. In the absence of citrate, diferric transferrin shows stepwise loss of iron atoms with the first atom of iron released at approximately pH 5.2. Citrate at physiologic concentrations (1.10(-3) M) or greater allows random iron removal at pH 6.5 or less. Iron dissociation from monoferric transferrin at acid pH, with or without citrate, is a random process. At pH 7.4, randomization of iron on transferrin takes from 3 to 6 h in the presence of millimolar concentrations of citrate. We conclude that at acid pH and in the presence of citrate concentrations likely to occur in vivo in the rat there is little scrambling of iron bound to transferrin."}
{"id": "PMID:30490", "title": "Origin of the ribityl side-chain of riboflavin from the ribose moiety of guanosine triphosphate in Pichia guilliermondii yeast.", "content": "In wild-type cells and some riboflavin-deficient mutants of P. guilliermondii GTP is transformed to the ribitylated intermediates 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine and 5-amino-2,6-dihydroxy-4-ribitylaminopyrimidine of the riboflavin biosynthetic path. We were able to show that these compounds were formed in vitro as well as in permeabilized cells by reactions including a reductive conversion of the product of GTP cyclohydrolase II action upon GTP. In order to analyse the pyrimidine derivates, 6,7-dimethyl-8-ribitylpterin and 6,7-dimethyl-8-ribityllumazine were synthesized by reaction of pyrimidines with diacetyl. The formation of ribitylated pyrimidines was shown to be strictly dependent on the presence of NADPH2. The data obtained indicate that the reductive step is catalyzed by a 2,5-diamino-6-hydroxy-4-ribosylaminopyrimidine-reductase. 6,7-Dimethyl-8-ribitylpterin and 6,7-dimethyl-8-ribityllumazine isolated from the incubation mixtures have been identified by chromatography and by their ultraviolet and fluorescence spectra.", "contents": "Origin of the ribityl side-chain of riboflavin from the ribose moiety of guanosine triphosphate in Pichia guilliermondii yeast. In wild-type cells and some riboflavin-deficient mutants of P. guilliermondii GTP is transformed to the ribitylated intermediates 2,5-diamino-6-hydroxy-4-ribitylaminopyrimidine and 5-amino-2,6-dihydroxy-4-ribitylaminopyrimidine of the riboflavin biosynthetic path. We were able to show that these compounds were formed in vitro as well as in permeabilized cells by reactions including a reductive conversion of the product of GTP cyclohydrolase II action upon GTP. In order to analyse the pyrimidine derivates, 6,7-dimethyl-8-ribitylpterin and 6,7-dimethyl-8-ribityllumazine were synthesized by reaction of pyrimidines with diacetyl. The formation of ribitylated pyrimidines was shown to be strictly dependent on the presence of NADPH2. The data obtained indicate that the reductive step is catalyzed by a 2,5-diamino-6-hydroxy-4-ribosylaminopyrimidine-reductase. 6,7-Dimethyl-8-ribitylpterin and 6,7-dimethyl-8-ribityllumazine isolated from the incubation mixtures have been identified by chromatography and by their ultraviolet and fluorescence spectra."}
{"id": "PMID:30491", "title": "Characterization of an agglutinin from human serum.", "content": "After exposure to serum, an agglutination of mitochondria from yeast, liver, heart and kidney was observed. The degree of agglutination was dependent on the ratio between the amount of serum proteins and mitochondrial protein. The serum protein which induced agglutination was bound irreversibly to the mitochondria, was heat stable and partly resistant to acidification. Maximal agglutination was observed at an ionic strength equal to 40 mM Tris, at pH 6.0-7.5. Preincubation of mitochondria with calcium ions at slightly acidic pH prevented the agglutination. Neuraminidase treatment of either serum or mitochondria had no effect upon the agglutination.", "contents": "Characterization of an agglutinin from human serum. After exposure to serum, an agglutination of mitochondria from yeast, liver, heart and kidney was observed. The degree of agglutination was dependent on the ratio between the amount of serum proteins and mitochondrial protein. The serum protein which induced agglutination was bound irreversibly to the mitochondria, was heat stable and partly resistant to acidification. Maximal agglutination was observed at an ionic strength equal to 40 mM Tris, at pH 6.0-7.5. Preincubation of mitochondria with calcium ions at slightly acidic pH prevented the agglutination. Neuraminidase treatment of either serum or mitochondria had no effect upon the agglutination."}
{"id": "PMID:30492", "title": "The relation between carbon monoxide binding and the conformational change of hemoglobin.", "content": "The spectral difference between normal and rapidly reacting deoxyhemoglobin (Sawicki and Gibson (1976), J. Biol Chem. 251:1533-1542) is used to study the relationship between CO binding to hemoglobin and the conformational changes to the rapidly reacting form in a combined flow-laser flash experiment. In both pH 7 phosphate buffer and pH 7 bis(2-hydroxy-ethyl)imino-tris (hydroxymethyl)methane buffer (bis-Tris) with 500 muM 2,3-diphosphoglycerate (DPG), the conformational change lags far behind CO binding; rapidly  reacting hemoglobin is not observed until more than 10% of the hemoglobin is liganded. In pH 9 borate buffer the formation of rapidly reacting hemoglobin leads CO binding by a significant amount. A simple two-state allosteric model (Monod et. al. (1965), J. Mol. Biol. 12:88-118) which assumed equivalence of the hemoglobin subunits in their reaction with CO was used to simulate the experimental results. In terms of the model, the conformational change lead observed at pH 9 suggests that significant conformational change has occurred after binding of only one CO molecule per tetramer. In the presence of phosphates good agreement between experimental results and simulations is obtained using parameter values suggested by previous experimental studies. The simulations suggest that the conformational change occurs after binding of three CO molecules.", "contents": "The relation between carbon monoxide binding and the conformational change of hemoglobin. The spectral difference between normal and rapidly reacting deoxyhemoglobin (Sawicki and Gibson (1976), J. Biol Chem. 251:1533-1542) is used to study the relationship between CO binding to hemoglobin and the conformational changes to the rapidly reacting form in a combined flow-laser flash experiment. In both pH 7 phosphate buffer and pH 7 bis(2-hydroxy-ethyl)imino-tris (hydroxymethyl)methane buffer (bis-Tris) with 500 muM 2,3-diphosphoglycerate (DPG), the conformational change lags far behind CO binding; rapidly  reacting hemoglobin is not observed until more than 10% of the hemoglobin is liganded. In pH 9 borate buffer the formation of rapidly reacting hemoglobin leads CO binding by a significant amount. A simple two-state allosteric model (Monod et. al. (1965), J. Mol. Biol. 12:88-118) which assumed equivalence of the hemoglobin subunits in their reaction with CO was used to simulate the experimental results. In terms of the model, the conformational change lead observed at pH 9 suggests that significant conformational change has occurred after binding of only one CO molecule per tetramer. In the presence of phosphates good agreement between experimental results and simulations is obtained using parameter values suggested by previous experimental studies. The simulations suggest that the conformational change occurs after binding of three CO molecules."}
{"id": "PMID:30493", "title": "Bicarbonate-chloride exchange in erythrocyte suspensions. Stopped-flow pH electrode measurements.", "content": "A pH-sensitive glass electrode was used in a temperature-controlled stopped-flow rapid reaction apparatus to determine rates of pH equilibration in red cell suspensions. The apparatus requires less than 2 ml of reactants. The electrode is insensitive to pressure and flow variations, and has a response time of < 5 ms. A 20% suspension of washed fresh human erythrocytes in saline at pH 7.7 containing NaHCO(3) and extracellular carbonic anhydrase is mixed with an equal volume of 30 mM phosphate buffer at pH 6.7. Within a few milliseconds after mixing, extracellular HCO(3) (-) reacts with H(+) to form CO(2), which enters the red cells and rehydrates to form HCO(3) (-), producing an electrochemical potential gradient for HCO(3) (-) from inside to outside the cells. HCO(3) (-) then leaves the cells in exchange for Cl(-), and extracellular pH increases as the HCO(3) (-) flowing out of the cells reacts with H(+). Flux of HCO(3) (-) is calculated from the dpH/dt during HCO(3) (-)-Cl(-) exchange, and a velocity constant is computed from the flux and the calculated intracellular and extracellular [HCO(3) (-)]. The activation energy for the exchange process is 18.6 kcal/mol between 5 degrees C and 17 degrees C (transition temperature), and 11.4 kcal/mol from 17 degrees C to 40 degrees C. The activation energies and transition temperature are not significantly altered in the presence of a potent anion exchange inhibitor (SITS), although the fluxes are markedly decreased. These findings suggest that the rate-limiting step in red cell anion exchange changes at 17 degrees C, either because of an alteration in the nature of the transport site or because of a transition in the physical state of membrane lipids affecting protein-lipid interactions.", "contents": "Bicarbonate-chloride exchange in erythrocyte suspensions. Stopped-flow pH electrode measurements. A pH-sensitive glass electrode was used in a temperature-controlled stopped-flow rapid reaction apparatus to determine rates of pH equilibration in red cell suspensions. The apparatus requires less than 2 ml of reactants. The electrode is insensitive to pressure and flow variations, and has a response time of < 5 ms. A 20% suspension of washed fresh human erythrocytes in saline at pH 7.7 containing NaHCO(3) and extracellular carbonic anhydrase is mixed with an equal volume of 30 mM phosphate buffer at pH 6.7. Within a few milliseconds after mixing, extracellular HCO(3) (-) reacts with H(+) to form CO(2), which enters the red cells and rehydrates to form HCO(3) (-), producing an electrochemical potential gradient for HCO(3) (-) from inside to outside the cells. HCO(3) (-) then leaves the cells in exchange for Cl(-), and extracellular pH increases as the HCO(3) (-) flowing out of the cells reacts with H(+). Flux of HCO(3) (-) is calculated from the dpH/dt during HCO(3) (-)-Cl(-) exchange, and a velocity constant is computed from the flux and the calculated intracellular and extracellular [HCO(3) (-)]. The activation energy for the exchange process is 18.6 kcal/mol between 5 degrees C and 17 degrees C (transition temperature), and 11.4 kcal/mol from 17 degrees C to 40 degrees C. The activation energies and transition temperature are not significantly altered in the presence of a potent anion exchange inhibitor (SITS), although the fluxes are markedly decreased. These findings suggest that the rate-limiting step in red cell anion exchange changes at 17 degrees C, either because of an alteration in the nature of the transport site or because of a transition in the physical state of membrane lipids affecting protein-lipid interactions."}
{"id": "PMID:30497", "title": "[Change in the concentration of nicotinamide nucleotides in rat brain and myocardium under the influence of factors inducing neurogenic dystrophy].", "content": "The content of nicotinamide dinucleotides in the brain and myocardium induced by electrical stimulation of rats and by injection of toxic noradrenaline doses was investigated. The total level of pyridine nucleotides and of their oxidized forms proved to be decreased, and the content of triphosphopyridine nucleotides and their synthesis activity rose. The data obtained point to disturbances of the redox processes and to increase of hexose monophosphate shunt activity in the tissues by neurogenic dystrophies induced by excessive irritation.", "contents": "[Change in the concentration of nicotinamide nucleotides in rat brain and myocardium under the influence of factors inducing neurogenic dystrophy]. The content of nicotinamide dinucleotides in the brain and myocardium induced by electrical stimulation of rats and by injection of toxic noradrenaline doses was investigated. The total level of pyridine nucleotides and of their oxidized forms proved to be decreased, and the content of triphosphopyridine nucleotides and their synthesis activity rose. The data obtained point to disturbances of the redox processes and to increase of hexose monophosphate shunt activity in the tissues by neurogenic dystrophies induced by excessive irritation."}
{"id": "PMID:30503", "title": "beta-Adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamine.", "content": "1 The effect of various beta-adrenoceptor blocking agents on the 5-hydroxytryptamine (5-HT)-induced hyperactivity response produced in rats by administration of tranylcypromine (10 mg/kg i.p.) followed by L-tryptophan (50 mg/kg i.p.) has been investigated. 2 (+/-)-Alprenolol, (+/-)-timolol, (+/-)-sotalol, (+/-)-pindolol (all at 40 mg/kg) all inhibited the hyperactivity response to some degree when given 45 min before the tranylcypromine, as did (+/-)-oxprenolol when given after the L-tryptophan. 3 beta-Adrenoceptor antagonists that are not found in the brain appreciable amount after peripheral injection, (+/-)-atenolol, (+/-)-practolol, (+/-)-labetalol and (+/-)-acebutalol, did not inhibit the 5-HT-mediated behaviour. 4 Neither the beta1-selective drug (+/-)-metoprolol, nor the beta2-selective drug (+/-)-butoxamine inhibited the behavioral response. 5 The drugs that blocked the 5-HT-mediated behaviour did not alter brain 5-HT concentrations, synthesis rate or the accumulation of 5-HT following tranylcypromine/L-tryptophan. However, they did inhibit the hyperactivity produced by the suggested 5-HT agonist, 5-methoxy N,N-dimethyltryptamine, indicating that the beta-adrenoceptor blocking drugs were inhibiting the post-synaptic 5-HT-mediated response. 6 Circling produced by methamphetamine (3 mg/kg) in unilateral nigro-striatal lesioned rats was not altered by alprenolol, sotalol, pindolol or metaprolol, indicating that these drugs do not alter dopamine-mediated behaviour. 7 It is concluded that non-selective (beta1 and beta2) adrenoceptor antagonists which have a high brain/blood ratio following their peripheral injection, block 5-HT-mediated behavioural responses in the rat.", "contents": "beta-Adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamine. 1 The effect of various beta-adrenoceptor blocking agents on the 5-hydroxytryptamine (5-HT)-induced hyperactivity response produced in rats by administration of tranylcypromine (10 mg/kg i.p.) followed by L-tryptophan (50 mg/kg i.p.) has been investigated. 2 (+/-)-Alprenolol, (+/-)-timolol, (+/-)-sotalol, (+/-)-pindolol (all at 40 mg/kg) all inhibited the hyperactivity response to some degree when given 45 min before the tranylcypromine, as did (+/-)-oxprenolol when given after the L-tryptophan. 3 beta-Adrenoceptor antagonists that are not found in the brain appreciable amount after peripheral injection, (+/-)-atenolol, (+/-)-practolol, (+/-)-labetalol and (+/-)-acebutalol, did not inhibit the 5-HT-mediated behaviour. 4 Neither the beta1-selective drug (+/-)-metoprolol, nor the beta2-selective drug (+/-)-butoxamine inhibited the behavioral response. 5 The drugs that blocked the 5-HT-mediated behaviour did not alter brain 5-HT concentrations, synthesis rate or the accumulation of 5-HT following tranylcypromine/L-tryptophan. However, they did inhibit the hyperactivity produced by the suggested 5-HT agonist, 5-methoxy N,N-dimethyltryptamine, indicating that the beta-adrenoceptor blocking drugs were inhibiting the post-synaptic 5-HT-mediated response. 6 Circling produced by methamphetamine (3 mg/kg) in unilateral nigro-striatal lesioned rats was not altered by alprenolol, sotalol, pindolol or metaprolol, indicating that these drugs do not alter dopamine-mediated behaviour. 7 It is concluded that non-selective (beta1 and beta2) adrenoceptor antagonists which have a high brain/blood ratio following their peripheral injection, block 5-HT-mediated behavioural responses in the rat."}
{"id": "PMID:30504", "title": "Occurrence of H1- and H2-histamine receptors in the guinea-pig gall bladder in situ.", "content": "1 Histamine has a dual action on the in situ gall bladder of the guinea-pig: a spasmogenic and a relaxant effect mediated through H1- and H2-receptor stimulation respectively. 2 The contracturant action, mimicked by 2-(2-aminoethyl) thiazole (a specific H1-receptor agonist), is blocked by mepyramine and the relaxation, mimicked by dimaprit (a specific H2-receptor agonist), is inhibited by cimetidine.", "contents": "Occurrence of H1- and H2-histamine receptors in the guinea-pig gall bladder in situ. 1 Histamine has a dual action on the in situ gall bladder of the guinea-pig: a spasmogenic and a relaxant effect mediated through H1- and H2-receptor stimulation respectively. 2 The contracturant action, mimicked by 2-(2-aminoethyl) thiazole (a specific H1-receptor agonist), is blocked by mepyramine and the relaxation, mimicked by dimaprit (a specific H2-receptor agonist), is inhibited by cimetidine."}
{"id": "PMID:30505", "title": "Release of 3H-purines from [3H]-adenine labelled rabbit kidney following sympathetic nerve stimulation, and its inhibition by alpha-adrenoceptor blockage.", "content": "1 Rabbit kidneys were isolated and perfused with Tyrode solution. Release of 3H-purines was studied after labeling of the adenine-nucleotide stores with [3H]adenine (more than 60% uptake during a single passage). 2 One hour after labelling the spontaneous 3H-outflow amounted to 0.1 to 0.2% of the total tissue content per minute. The release rate was enhanced following nerve stimulation (3 to 10 Hz), or brief infusion of noradrenaline (0.1 to 2.4 microgram i.a.). Release of radioactivity was also enhanced by angiotensin II, by interruption of perfusion flow for 0.5 to 2 min and by hypoxia (5 to 25% O2). 3 The release of tracer induced by nerve stimulation or noradrenaline was markedly reduced or abolished by phenoxybenzamine, which also inhibited the vasoconstrictor response. The release following angiotensin II, ischaemia and hypoxia could not be antagonized by this alpha-adrenoceptor antagonist. 4 the radioactivity in the kidney was predominantly in nucleotide form, while that released was composed mainly of nucleosides, of which adenosine predominated. 5 The results indicate that in the rabbit kidney vasocontriction, arterial clamping or reduced perfusion oxygen tension, cause release of adenosine and related compounds. In view of the reported actions of adenosine on noradrenaline effects and release in the kidney a possible physiological role is discussed.", "contents": "Release of 3H-purines from [3H]-adenine labelled rabbit kidney following sympathetic nerve stimulation, and its inhibition by alpha-adrenoceptor blockage. 1 Rabbit kidneys were isolated and perfused with Tyrode solution. Release of 3H-purines was studied after labeling of the adenine-nucleotide stores with [3H]adenine (more than 60% uptake during a single passage). 2 One hour after labelling the spontaneous 3H-outflow amounted to 0.1 to 0.2% of the total tissue content per minute. The release rate was enhanced following nerve stimulation (3 to 10 Hz), or brief infusion of noradrenaline (0.1 to 2.4 microgram i.a.). Release of radioactivity was also enhanced by angiotensin II, by interruption of perfusion flow for 0.5 to 2 min and by hypoxia (5 to 25% O2). 3 The release of tracer induced by nerve stimulation or noradrenaline was markedly reduced or abolished by phenoxybenzamine, which also inhibited the vasoconstrictor response. The release following angiotensin II, ischaemia and hypoxia could not be antagonized by this alpha-adrenoceptor antagonist. 4 the radioactivity in the kidney was predominantly in nucleotide form, while that released was composed mainly of nucleosides, of which adenosine predominated. 5 The results indicate that in the rabbit kidney vasocontriction, arterial clamping or reduced perfusion oxygen tension, cause release of adenosine and related compounds. In view of the reported actions of adenosine on noradrenaline effects and release in the kidney a possible physiological role is discussed."}
{"id": "PMID:30506", "title": "Differences between presynaptic and postsynaptic alpha-adrenoceptors in the isolated nictitating membrane of the cat: effects of metanephrine and tolazoline.", "content": "The alpha-adrenoceptor blocking agent, tolazoline, and the O-methylated metabolite of adrenaline, metanephrine, produced a concentration-dependent increase of tension in the smooth muscle of the cat isolated nictitating membrane. These effects were considered to be due to the activation of postsynaptic alpha-adrenoceptors. 2 The responses to nerve stimulation of this muscle were neither potentiated nor blocked by tolazoline (0.1 to 10 micrometer) or metanephrine (1 to 10 micrometer). 3 3H-transmitter overflow evoked by electrical stimulation was not modified by tolazoline or metanephrine in concentrations in which these drugs stimulated the postsynaptic alpha-adrenoceptors. 4 Since tolazoline and metanephrine failed to activate the presynaptic alpha-adrenoceptors of the cat nictitating membrane under experimental conditions in which they stimulated the postsynaptic alpha-adrenoceptors, these results further support the view that the presynaptic (alpha2) adrenoceptors differ from the postsynaptic (alpha1) adrenoceptors.", "contents": "Differences between presynaptic and postsynaptic alpha-adrenoceptors in the isolated nictitating membrane of the cat: effects of metanephrine and tolazoline. The alpha-adrenoceptor blocking agent, tolazoline, and the O-methylated metabolite of adrenaline, metanephrine, produced a concentration-dependent increase of tension in the smooth muscle of the cat isolated nictitating membrane. These effects were considered to be due to the activation of postsynaptic alpha-adrenoceptors. 2 The responses to nerve stimulation of this muscle were neither potentiated nor blocked by tolazoline (0.1 to 10 micrometer) or metanephrine (1 to 10 micrometer). 3 3H-transmitter overflow evoked by electrical stimulation was not modified by tolazoline or metanephrine in concentrations in which these drugs stimulated the postsynaptic alpha-adrenoceptors. 4 Since tolazoline and metanephrine failed to activate the presynaptic alpha-adrenoceptors of the cat nictitating membrane under experimental conditions in which they stimulated the postsynaptic alpha-adrenoceptors, these results further support the view that the presynaptic (alpha2) adrenoceptors differ from the postsynaptic (alpha1) adrenoceptors."}
{"id": "PMID:30507", "title": "Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum.", "content": "1 The presynaptic alpha-adrenoceptors located on the terminals of the cholinergic nerves of the guineapig myenteric plexus have been characterized according to their sensitivities to alpha-adrenoceptor agonists and antagonists.2 Electrical stimulation of the cholinergic nerves supplying the longitudinal muscle of the guinea-pig ileum caused a twitch response. Clonidine caused a concentration-dependent inhibition of the twitch response; the maximum inhibition obtained was 80 to 95% of the twitch response. Oxymetazoline and xylazine were qualitatively similar to clonidine but were about 5 times less potent. Phenylephrine and methoxamine also inhibited the twitch response but were at least 10,000 times less potent than clonidine.3 The twitch-inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine, were reversed by piperoxan (0.3 to 1.0 mug/ml).4 Lysergic acid diethylamide (LSD) inhibited the twitch response, but also increased the basal tone of the ileum. Mepyramine prevented the increase in tone but did not affect the inhibitory action of LSD. Piperoxan or phentolamine only partially antagonized the inhibitory effect of LSD.5 Phentolamine, yohimbine, piperoxan and tolazoline were potent, competitive antagonists of the inhibitory effect of clonidine with pA(2) values of 8.51, 7.78, 7.64 and 6.57 respectively.6 Thymoxamine was a weak antagonist of clonidine; it also antagonized the twitch-inhibitory effect of morphine. Thus, its effect against clonidine is probably not mediated specifically at presynaptic alpha-adrenoceptors.7 Labetalol, itself, depressed the twitch response but did not antagonize the inhibitory effect of clonidine on the residual twitch.8 The results demonstrate that the presynaptic alpha-adrenoceptors in the guinea-pig ileum are of the same type as those located presynaptically in sympathetically innervated tissues. They are alpha(2)-adrenoceptors and are different from those located postsynaptically.", "contents": "Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. 1 The presynaptic alpha-adrenoceptors located on the terminals of the cholinergic nerves of the guineapig myenteric plexus have been characterized according to their sensitivities to alpha-adrenoceptor agonists and antagonists.2 Electrical stimulation of the cholinergic nerves supplying the longitudinal muscle of the guinea-pig ileum caused a twitch response. Clonidine caused a concentration-dependent inhibition of the twitch response; the maximum inhibition obtained was 80 to 95% of the twitch response. Oxymetazoline and xylazine were qualitatively similar to clonidine but were about 5 times less potent. Phenylephrine and methoxamine also inhibited the twitch response but were at least 10,000 times less potent than clonidine.3 The twitch-inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine, were reversed by piperoxan (0.3 to 1.0 mug/ml).4 Lysergic acid diethylamide (LSD) inhibited the twitch response, but also increased the basal tone of the ileum. Mepyramine prevented the increase in tone but did not affect the inhibitory action of LSD. Piperoxan or phentolamine only partially antagonized the inhibitory effect of LSD.5 Phentolamine, yohimbine, piperoxan and tolazoline were potent, competitive antagonists of the inhibitory effect of clonidine with pA(2) values of 8.51, 7.78, 7.64 and 6.57 respectively.6 Thymoxamine was a weak antagonist of clonidine; it also antagonized the twitch-inhibitory effect of morphine. Thus, its effect against clonidine is probably not mediated specifically at presynaptic alpha-adrenoceptors.7 Labetalol, itself, depressed the twitch response but did not antagonize the inhibitory effect of clonidine on the residual twitch.8 The results demonstrate that the presynaptic alpha-adrenoceptors in the guinea-pig ileum are of the same type as those located presynaptically in sympathetically innervated tissues. They are alpha(2)-adrenoceptors and are different from those located postsynaptically."}
{"id": "PMID:30510", "title": "Radiologic manifestations of epidemic haemorrhagic fever with renal syndrome.", "content": "Epidemic haemorrhagic fever is a viral disease characterized by acute febrile onset followed by profound renal dysfunction. The endemic areas are widespread throughout the Eurasian continent and the Japanese islands. The patient with EHF usually seeks medical care as an emergency for an \"acute abdomen\". Consequently the X-ray examination becomes an essential part of the clinical study. We analysed the plain abdomen and chest films of 62 patients with this disease. The radiologic manifestations represented diffuse capillary damage with resultant oedema and haemorrhage, particularly in the retro-peritoneal space. Abnormal findings were seen in 94% of the patients on the plain abdomen, and in 63% on the chest film. The most significant finding was obliteration and blurring of anatomical detail in both intra- and retro-peritoneal cavities and renal enlargement. We believe that simultaneous presence of oedema and effusion in both intra- and retro-peritoneal cavities along with renal enlargement is in practice pathognomic of EHF. Obliteration of the renal outline and cardiomegaly with overt lung oedema was associated with the most severe renal dysfunction.", "contents": "Radiologic manifestations of epidemic haemorrhagic fever with renal syndrome. Epidemic haemorrhagic fever is a viral disease characterized by acute febrile onset followed by profound renal dysfunction. The endemic areas are widespread throughout the Eurasian continent and the Japanese islands. The patient with EHF usually seeks medical care as an emergency for an \"acute abdomen\". Consequently the X-ray examination becomes an essential part of the clinical study. We analysed the plain abdomen and chest films of 62 patients with this disease. The radiologic manifestations represented diffuse capillary damage with resultant oedema and haemorrhage, particularly in the retro-peritoneal space. Abnormal findings were seen in 94% of the patients on the plain abdomen, and in 63% on the chest film. The most significant finding was obliteration and blurring of anatomical detail in both intra- and retro-peritoneal cavities and renal enlargement. We believe that simultaneous presence of oedema and effusion in both intra- and retro-peritoneal cavities along with renal enlargement is in practice pathognomic of EHF. Obliteration of the renal outline and cardiomegaly with overt lung oedema was associated with the most severe renal dysfunction."}
{"id": "PMID:30519", "title": "Glutamate secretion and NAD(P)H levels during calcium-dependent depolarization of slices of the dentate gyrus.", "content": "Evidence from studies involving release, postsynaptic responses, inactivation, storage and synthesis etc. support the contention that glutamate may be the transmitter of the perforant input to the granule cells in the dentate gyrus of the hippocampus. In the present report the release of endogenous glutamate and the levels of reduced pyridine nucleotides (NAD(P)H) has been measured in parallel experiments on slices from the dentate gyrus of the hippocampus. A Ca-dependent release of glutamate is evoked by tissue depolarization caused either with electrical field stimulation or with elevated KC1. Electrical stimulation induced a transient increase in tissue NAD(P)H levels, the increase being inhibited by approximately 50% during Ca-free conditions. KC1 stimulation, on the other hand, produced a long-lasting decrease in NAD(P)H, the decrease being halved in the absense of Ca. A metabolic relation between stimulus secretion and energy utilization is discussed.", "contents": "Glutamate secretion and NAD(P)H levels during calcium-dependent depolarization of slices of the dentate gyrus. Evidence from studies involving release, postsynaptic responses, inactivation, storage and synthesis etc. support the contention that glutamate may be the transmitter of the perforant input to the granule cells in the dentate gyrus of the hippocampus. In the present report the release of endogenous glutamate and the levels of reduced pyridine nucleotides (NAD(P)H) has been measured in parallel experiments on slices from the dentate gyrus of the hippocampus. A Ca-dependent release of glutamate is evoked by tissue depolarization caused either with electrical field stimulation or with elevated KC1. Electrical stimulation induced a transient increase in tissue NAD(P)H levels, the increase being inhibited by approximately 50% during Ca-free conditions. KC1 stimulation, on the other hand, produced a long-lasting decrease in NAD(P)H, the decrease being halved in the absense of Ca. A metabolic relation between stimulus secretion and energy utilization is discussed."}
{"id": "PMID:30523", "title": "A thermodynamic analysis of the secondary transition in the spontaneous precipitation of calcium phosphate.", "content": "A thermodynamic analysis has been made of the secondary transition stage in the spontaneous precipitation of calcium phosphate following the amorphous-crystalline transformation. The first formed crystalline material has a solubility similar to that of octacalcium phosphate (OCP) and the computed thermodynamic solubility product remains invariant in the pH range 7.00--8.60. The duration of the secondary stage is sensitive to pH and the transition appears to occur by hydrolysis of the first formed OCP-like phase to a more basic apatitic phase with a tricalcium phosphate (TCP) stoichiometry. The crystalline material at the end of this transition has an invariant solubility product, in the pH range 7.00 to 8.60, when the TCP-like molecular formula is assumed. Changes in the solution chemistry which accompany the solid-to-solid transitions are consistent with the above conclusions. The results of this study are also consistent with those of a previous study which suggest that the stability of the amorphous calcium phosphate phase is dependent upon the instability of the solution phase with respect to OCP formation.", "contents": "A thermodynamic analysis of the secondary transition in the spontaneous precipitation of calcium phosphate. A thermodynamic analysis has been made of the secondary transition stage in the spontaneous precipitation of calcium phosphate following the amorphous-crystalline transformation. The first formed crystalline material has a solubility similar to that of octacalcium phosphate (OCP) and the computed thermodynamic solubility product remains invariant in the pH range 7.00--8.60. The duration of the secondary stage is sensitive to pH and the transition appears to occur by hydrolysis of the first formed OCP-like phase to a more basic apatitic phase with a tricalcium phosphate (TCP) stoichiometry. The crystalline material at the end of this transition has an invariant solubility product, in the pH range 7.00 to 8.60, when the TCP-like molecular formula is assumed. Changes in the solution chemistry which accompany the solid-to-solid transitions are consistent with the above conclusions. The results of this study are also consistent with those of a previous study which suggest that the stability of the amorphous calcium phosphate phase is dependent upon the instability of the solution phase with respect to OCP formation."}
{"id": "PMID:30524", "title": "The role of renal nerves in the response to dipsogenic stimuli in the rat.", "content": "The effect of bilateral renal denervation on water intake and urine volume during specific thirst challenges was studied in rats. Renal denervation attenuated significantly the drinking response elicited by the administration of 30% polyethylene glycol (PG, extracellular challenge) but had no effect on the drinking response after an intracellular challenge (2.5 M NaCl) or after a 24-h water deprivation period. Furthermore, during a PG challenge total water intake was the same in two groups of rats, one with denervated kidneys and the other with beta-adrenergic neural activity in efferent renal nerves eliminated by blocking agents. Urine volumes were not affected by PG administration or water deprivation in denervated rats but were increased significantly after administration of 2.5 M NaCl. These results indicate that renal nerves play an important role in the physiological processes controlling extracellular thirst, and suggest that this role may be related to the neural control of release of renin.", "contents": "The role of renal nerves in the response to dipsogenic stimuli in the rat. The effect of bilateral renal denervation on water intake and urine volume during specific thirst challenges was studied in rats. Renal denervation attenuated significantly the drinking response elicited by the administration of 30% polyethylene glycol (PG, extracellular challenge) but had no effect on the drinking response after an intracellular challenge (2.5 M NaCl) or after a 24-h water deprivation period. Furthermore, during a PG challenge total water intake was the same in two groups of rats, one with denervated kidneys and the other with beta-adrenergic neural activity in efferent renal nerves eliminated by blocking agents. Urine volumes were not affected by PG administration or water deprivation in denervated rats but were increased significantly after administration of 2.5 M NaCl. These results indicate that renal nerves play an important role in the physiological processes controlling extracellular thirst, and suggest that this role may be related to the neural control of release of renin."}
{"id": "PMID:30526", "title": "Pharmacological studies on the pulmonary vein of the horse. I. Effects of selected spasmogens.", "content": "Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (BK), carbachol (Carb), and phenylephrine (phen) were studied. The order of contractile effectiveness for the agonists on the vein was found to be 5HT greater than H greater than Bk greater than Phen greater than Carb, although H consistently produced the greatest maximal effects. H1-receptors appeared to mediate H contractions while H2-receptors had no measurable effect. 5HT responses were mediated directly by 'D-type' smooth muscle receptors. Bk produced contractions but of a lesser magnitude than either H or 5HT. Varying degrees of tachyphylaxis were observed for each agent. alpha-Adrenergic receptor stimulation by Phen initiated low-magnitude contractions whereas Carb exhibited virtually no activity on the pulmonary vein. Contractile responses of pulmonary veins to various spasmogens may contribute to the equine asthmatic response by raising vascular hydrostatic pressure, thereby enhancing edema formation.", "contents": "Pharmacological studies on the pulmonary vein of the horse. I. Effects of selected spasmogens. Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (BK), carbachol (Carb), and phenylephrine (phen) were studied. The order of contractile effectiveness for the agonists on the vein was found to be 5HT greater than H greater than Bk greater than Phen greater than Carb, although H consistently produced the greatest maximal effects. H1-receptors appeared to mediate H contractions while H2-receptors had no measurable effect. 5HT responses were mediated directly by 'D-type' smooth muscle receptors. Bk produced contractions but of a lesser magnitude than either H or 5HT. Varying degrees of tachyphylaxis were observed for each agent. alpha-Adrenergic receptor stimulation by Phen initiated low-magnitude contractions whereas Carb exhibited virtually no activity on the pulmonary vein. Contractile responses of pulmonary veins to various spasmogens may contribute to the equine asthmatic response by raising vascular hydrostatic pressure, thereby enhancing edema formation."}
{"id": "PMID:30527", "title": "The ganglionic blocking properties of the cholinesterase reactivator, HS-6.", "content": "Following intravenous administration of the cholinesterase reactivator HS-6 (30 mg/kg), blood pressure fell (up to 50 mmHg) and maximal blood levels of HS-6 reached 242 microgram/ml. HS-6 attenuated the pressor response resulting from carotid occlusion and the depressor effect of vagal stimulation. Doses of HS-6 below those used to protect against soman in different animal species (10--30 mumol/kg) progressively blocked the ganglion-stimulating effects of nicotine and dimethylphenylpiperazinium but not the pressor effect following adrenaline, a pattern similar to that produced by hexamethonium but only 1/84 as potent. HS-6, like hexamethonium and mecamylamine, progressively blocked the contraction of the nictitating membrane of the cat resulting from preganglionic stimulation. The results indicate that HS-6 possesses ganglion-blocking properties at doses likely to be used in the protection against soman poisoning. The ganglion-blocking properties of the drug may be a factor in the beneficial effects of HS-6.", "contents": "The ganglionic blocking properties of the cholinesterase reactivator, HS-6. Following intravenous administration of the cholinesterase reactivator HS-6 (30 mg/kg), blood pressure fell (up to 50 mmHg) and maximal blood levels of HS-6 reached 242 microgram/ml. HS-6 attenuated the pressor response resulting from carotid occlusion and the depressor effect of vagal stimulation. Doses of HS-6 below those used to protect against soman in different animal species (10--30 mumol/kg) progressively blocked the ganglion-stimulating effects of nicotine and dimethylphenylpiperazinium but not the pressor effect following adrenaline, a pattern similar to that produced by hexamethonium but only 1/84 as potent. HS-6, like hexamethonium and mecamylamine, progressively blocked the contraction of the nictitating membrane of the cat resulting from preganglionic stimulation. The results indicate that HS-6 possesses ganglion-blocking properties at doses likely to be used in the protection against soman poisoning. The ganglion-blocking properties of the drug may be a factor in the beneficial effects of HS-6."}
{"id": "PMID:30528", "title": "A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones.", "content": "The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level.", "contents": "A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones. The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level."}
{"id": "PMID:30529", "title": "Intracellular actions of monoamine transmitters.", "content": "Intracellular injections of noradrenaline or dopamine in spinal motoneurones of cats have a clear depolarizing action associated with particularly marked depression of spike potentials and their after-hyperpolarization, but with little slowing-down of the falling phase of the action potential. These effects are associated with an increase in input resistance, and they are reversible and reproducible in the same neurone. Intracellular injections of 5-hydroxytryptamine have some depolarizing action and increased input resistance, but they produced no comparable depression of the action potential and tended to enhance the after-potentials and increase excitability. It is concluded that changes in intracellular levels of monoamines, whether physiological or drug induced, may be of significance for central neuronal function.", "contents": "Intracellular actions of monoamine transmitters. Intracellular injections of noradrenaline or dopamine in spinal motoneurones of cats have a clear depolarizing action associated with particularly marked depression of spike potentials and their after-hyperpolarization, but with little slowing-down of the falling phase of the action potential. These effects are associated with an increase in input resistance, and they are reversible and reproducible in the same neurone. Intracellular injections of 5-hydroxytryptamine have some depolarizing action and increased input resistance, but they produced no comparable depression of the action potential and tended to enhance the after-potentials and increase excitability. It is concluded that changes in intracellular levels of monoamines, whether physiological or drug induced, may be of significance for central neuronal function."}
{"id": "PMID:30530", "title": "Purification and properties of amylase produced by a moderately halophilic Acinetobacter sp.", "content": "A moderately halophilic Acinetobacter sp., capable of producing dextrinogenic amylase, was isolated from sea-sands. Maximum enzyme production was obtained when the bacterium was cultivated aerobically in media containing 1 to 2M NaCl or 1M KCl. Two kinds of amylase, amylases I and II were purified from the culture filtrate to an electrophoretically homogenous state by glycogen-complex formation, DEAE-Sephadex A-50 chromatography, and Sephadex G-200 gel filtration. Both enzymes had maximal activity at pH 7.0 in 0.2 to 0.6 M NaCl or KCl at 50 to 55 degrees C. The activities were lost by dialysis against distilled water. Molecular weights for amylases I and II were estimated to be 55 000 and 65 000 respectively by SDS-gel electrophoresis. The action pattern on amylose, soluble starch, and glycogen showed that the products were maltose and maltotriose.", "contents": "Purification and properties of amylase produced by a moderately halophilic Acinetobacter sp. A moderately halophilic Acinetobacter sp., capable of producing dextrinogenic amylase, was isolated from sea-sands. Maximum enzyme production was obtained when the bacterium was cultivated aerobically in media containing 1 to 2M NaCl or 1M KCl. Two kinds of amylase, amylases I and II were purified from the culture filtrate to an electrophoretically homogenous state by glycogen-complex formation, DEAE-Sephadex A-50 chromatography, and Sephadex G-200 gel filtration. Both enzymes had maximal activity at pH 7.0 in 0.2 to 0.6 M NaCl or KCl at 50 to 55 degrees C. The activities were lost by dialysis against distilled water. Molecular weights for amylases I and II were estimated to be 55 000 and 65 000 respectively by SDS-gel electrophoresis. The action pattern on amylose, soluble starch, and glycogen showed that the products were maltose and maltotriose."}
{"id": "PMID:30533", "title": "Effects of antianxiety agents on relaxation training: a preliminary investigation.", "content": "The purpose of this preliminary study was to investigate the effects of certain antianxiety agents, that is, minor tranquilizers, sedatives, and hypnotics, on relaxation training. Twelve inpatients and two outpatients were referred to group relaxation training because of tension-anxiety complaints and underwent three training sessions. Results for those patients who were not having any psychotropic medication (Relaxation Only group) were compared with results for those who were receiving anxiolytic drugs (Medication-Relaxation group). Patients in the second group were on antianxiety medication prior to and during relaxation training. Self-report measures indicate that the Relaxation Only group benefited more from relaxation training and showed more treatment generalization effects. The results are interpreted as lending some support to the view that antianxiety drugs may have an interfering effect on relaxation training. Implications and limitations of the study are discussed.", "contents": "Effects of antianxiety agents on relaxation training: a preliminary investigation. The purpose of this preliminary study was to investigate the effects of certain antianxiety agents, that is, minor tranquilizers, sedatives, and hypnotics, on relaxation training. Twelve inpatients and two outpatients were referred to group relaxation training because of tension-anxiety complaints and underwent three training sessions. Results for those patients who were not having any psychotropic medication (Relaxation Only group) were compared with results for those who were receiving anxiolytic drugs (Medication-Relaxation group). Patients in the second group were on antianxiety medication prior to and during relaxation training. Self-report measures indicate that the Relaxation Only group benefited more from relaxation training and showed more treatment generalization effects. The results are interpreted as lending some support to the view that antianxiety drugs may have an interfering effect on relaxation training. Implications and limitations of the study are discussed."}
{"id": "PMID:30534", "title": "Therapeutic trials in tardive dyskinesia.", "content": "The search for a treatment of tardive dyskinesia has generally been guided by the putative biochemical mechanisms underlying the extrapyramidal disorders, but no markedly effective treatment has yet been found. The currently postulated mechanism in tardive dyskinesia involves namely an imbalance between the central dopamine-acetylcholine systems whose balance may also be influenced by neuroendocrine factors. The agents reported having some clinical efficacy in the management of this neurological complication act on these systems. The clinical investigation for the treatment of tardive dyskinesia is laborious and raises several problems that could account for the unpredictability and the discrepancies in results. These problems can be divided into three broad categories: patient variables, experimental treatment variables and methodological variables. These variables are discussed and some suggestions made.", "contents": "Therapeutic trials in tardive dyskinesia. The search for a treatment of tardive dyskinesia has generally been guided by the putative biochemical mechanisms underlying the extrapyramidal disorders, but no markedly effective treatment has yet been found. The currently postulated mechanism in tardive dyskinesia involves namely an imbalance between the central dopamine-acetylcholine systems whose balance may also be influenced by neuroendocrine factors. The agents reported having some clinical efficacy in the management of this neurological complication act on these systems. The clinical investigation for the treatment of tardive dyskinesia is laborious and raises several problems that could account for the unpredictability and the discrepancies in results. These problems can be divided into three broad categories: patient variables, experimental treatment variables and methodological variables. These variables are discussed and some suggestions made."}
{"id": "PMID:30536", "title": "Carcinoembryonic antigen (CEA) and other tumor markers in ovarian and cervical cancer.", "content": "Combinations of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (GGT), pregnancy-associated macroglobulin (PAM) and placenta-like alkaline phosphatase (PLAP) were studied in groups of patients with ovarian and cervical cancer. In ovarian cancer, only CEA and PLAP levels appeared to reflect tumor burden and were complementary in detecting active disease. In cervical cancer, CEA and GGT reflected tumor burden, while PLAP showed just the reverse--the highest degree of positivity being present in minimal disease. PLAP positivity was even more pronounced in patients with cervical dysplasia and carcinoma in situ while CEA and GGT were negative. The data indicate that the use of marker combinations can improve our capacity to detect minimal disease and provide information regarding tumor biology that may not be available by studying individual markers or by other means. It remains to be determined whether the use of tumor markers can influence existing therapy sufficiently to alter the outcome in cancers which are notoriously difficult to treat.", "contents": "Carcinoembryonic antigen (CEA) and other tumor markers in ovarian and cervical cancer. Combinations of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (GGT), pregnancy-associated macroglobulin (PAM) and placenta-like alkaline phosphatase (PLAP) were studied in groups of patients with ovarian and cervical cancer. In ovarian cancer, only CEA and PLAP levels appeared to reflect tumor burden and were complementary in detecting active disease. In cervical cancer, CEA and GGT reflected tumor burden, while PLAP showed just the reverse--the highest degree of positivity being present in minimal disease. PLAP positivity was even more pronounced in patients with cervical dysplasia and carcinoma in situ while CEA and GGT were negative. The data indicate that the use of marker combinations can improve our capacity to detect minimal disease and provide information regarding tumor biology that may not be available by studying individual markers or by other means. It remains to be determined whether the use of tumor markers can influence existing therapy sufficiently to alter the outcome in cancers which are notoriously difficult to treat."}
{"id": "PMID:30537", "title": "Seminoma in a 12-year-old male with 46 XY/45 XO karyotype.", "content": "A pure seminoma in a 12-year-old boy with an undescended testis and 46 XY/45 XO karyotype is presented. The relationships between an undescended testis, an abnormal karyotype, dysgenetic gonads and cancer are discussed.", "contents": "Seminoma in a 12-year-old male with 46 XY/45 XO karyotype. A pure seminoma in a 12-year-old boy with an undescended testis and 46 XY/45 XO karyotype is presented. The relationships between an undescended testis, an abnormal karyotype, dysgenetic gonads and cancer are discussed."}
{"id": "PMID:30539", "title": "Adenosine triphosphate induced change in light scattering of isolated basal bodies.", "content": "Suspensions of isolated basal bodies undergo a characteristic decrease in turbidity following their exposure to 10(-3) M ATP. Typically, turbidity changes range from 8% to 20%, depending on the preparation, with an average change of 12%. Nucleotides other than ATP did not cause a turbidity decrease. The reaction has a pH optimum of pH 8.5 and is inhibited by concentrations of divalent cations greater than 2 X 10(-3) M. These results indicate that ATP induces a conformational change in the basal body that may be related to its activity in the cell.", "contents": "Adenosine triphosphate induced change in light scattering of isolated basal bodies. Suspensions of isolated basal bodies undergo a characteristic decrease in turbidity following their exposure to 10(-3) M ATP. Typically, turbidity changes range from 8% to 20%, depending on the preparation, with an average change of 12%. Nucleotides other than ATP did not cause a turbidity decrease. The reaction has a pH optimum of pH 8.5 and is inhibited by concentrations of divalent cations greater than 2 X 10(-3) M. These results indicate that ATP induces a conformational change in the basal body that may be related to its activity in the cell."}
{"id": "PMID:30541", "title": "Properties of the cadmium and selenium complex formed in rat plasma in vivo and in vitro.", "content": "Following the simultaneous subcutaneous administration of CdCl2 and Na2SeO3 to rats, evidence of a Cd-Se complex was detected in plasma by gel filtration chromatography. A similar complex was found in plasma after incubation of selenite, Cd, rat erythrocytes, and plasma in vitro, and after incubation of H2Se, Cd, and plasma in vitro. No interaction of selenite, selanete, or selenodiglutathione with Cd and plasma in the absence of erythrocytes in vitro was noted. Characterization by gel filtration, ion-exchange chromatography, affinity chromatography, and ammonium sulfate fractionation showed that these Cd-Se complexes are similar. The results support the hypothesis that H2Se or a similarly reduced selenide is the product of selenite metabolism by rat erythrocytes. Hydrogen selenide also altered the distribution of inorganic mercury in rat plasma in vitro in such a way that the apparent molecular weights of the Se-Hg and Cd-Se complexes associated with protein were similar. Hydrogen selenide had no effect upon the distribution of methylmercury in plasma. The stability of the Cd-Se complex in plasma depended upon the integrity of the native protein components, as shown by incubation with Proteinase K. The properties of the complex suggested that it existed in a single form associated with different plasma components under various conditions.", "contents": "Properties of the cadmium and selenium complex formed in rat plasma in vivo and in vitro. Following the simultaneous subcutaneous administration of CdCl2 and Na2SeO3 to rats, evidence of a Cd-Se complex was detected in plasma by gel filtration chromatography. A similar complex was found in plasma after incubation of selenite, Cd, rat erythrocytes, and plasma in vitro, and after incubation of H2Se, Cd, and plasma in vitro. No interaction of selenite, selanete, or selenodiglutathione with Cd and plasma in the absence of erythrocytes in vitro was noted. Characterization by gel filtration, ion-exchange chromatography, affinity chromatography, and ammonium sulfate fractionation showed that these Cd-Se complexes are similar. The results support the hypothesis that H2Se or a similarly reduced selenide is the product of selenite metabolism by rat erythrocytes. Hydrogen selenide also altered the distribution of inorganic mercury in rat plasma in vitro in such a way that the apparent molecular weights of the Se-Hg and Cd-Se complexes associated with protein were similar. Hydrogen selenide had no effect upon the distribution of methylmercury in plasma. The stability of the Cd-Se complex in plasma depended upon the integrity of the native protein components, as shown by incubation with Proteinase K. The properties of the complex suggested that it existed in a single form associated with different plasma components under various conditions."}
{"id": "PMID:30542", "title": "Lymphocyte surface poisons: disulfides and thiolsulfonates.", "content": "Eight disulfides (I-VIII) and a thiolsulfonate (IX) were promising blocking agents of lymphocytes in graft-versus-host reactions (GvHR) without comensurate intracellular effects. The blocking effects were assayed through inhibition of the local GvHR after parental lymphocytes had been incubated with agents at suitable concentrations and then inoculated into F1 hybrid offspring. The intracellular effects were assessed beforehand by measuring the inhibition of [6-3H]thymidine incorporation by lymphocytes in the presence of a wide range of concentrations of agents. Concentration levels which induced no greater than approx. 50% inhibition of the [6-3H] thymidine incorporation were considered to reflect sufficiently small intracellular effects and were used for the subsequent GvHR comparisons. Cellular survival always was 90% or more for the GvHR tests (unless stated otherwise), even when inhibition of thymidine incorporation was as high as 50%; hence the thymidine data are useful not only as guides for dose levels in the GvHR but also as leads to new agents that may show immunosuppressive or anti-leukemic activity through intracellular effects. Structural specificity of the active compounds as cell-surface poisons is evidenced by little or no activity (less than 30% inhibition of GvHR) of 28 other disulfides, 2 trisulfides, 2 Bunte salts, and 8 other thiolsulfonates. Active agents may owe this function to replacement of the H of SH in cell-surface thiol receptors by an SR group. Glutathione did not significantly inactivate agents, probably because the products of reaction also are active disulfides. When two agents (III, IX) were given orally or intraperitoneally to F1 hybrid recipients of untreated parental cells, doses of 10--15 mg/kg produced a GvHR inhibition of 17--53%.", "contents": "Lymphocyte surface poisons: disulfides and thiolsulfonates. Eight disulfides (I-VIII) and a thiolsulfonate (IX) were promising blocking agents of lymphocytes in graft-versus-host reactions (GvHR) without comensurate intracellular effects. The blocking effects were assayed through inhibition of the local GvHR after parental lymphocytes had been incubated with agents at suitable concentrations and then inoculated into F1 hybrid offspring. The intracellular effects were assessed beforehand by measuring the inhibition of [6-3H]thymidine incorporation by lymphocytes in the presence of a wide range of concentrations of agents. Concentration levels which induced no greater than approx. 50% inhibition of the [6-3H] thymidine incorporation were considered to reflect sufficiently small intracellular effects and were used for the subsequent GvHR comparisons. Cellular survival always was 90% or more for the GvHR tests (unless stated otherwise), even when inhibition of thymidine incorporation was as high as 50%; hence the thymidine data are useful not only as guides for dose levels in the GvHR but also as leads to new agents that may show immunosuppressive or anti-leukemic activity through intracellular effects. Structural specificity of the active compounds as cell-surface poisons is evidenced by little or no activity (less than 30% inhibition of GvHR) of 28 other disulfides, 2 trisulfides, 2 Bunte salts, and 8 other thiolsulfonates. Active agents may owe this function to replacement of the H of SH in cell-surface thiol receptors by an SR group. Glutathione did not significantly inactivate agents, probably because the products of reaction also are active disulfides. When two agents (III, IX) were given orally or intraperitoneally to F1 hybrid recipients of untreated parental cells, doses of 10--15 mg/kg produced a GvHR inhibition of 17--53%."}
{"id": "PMID:30543", "title": "Correlation between tissue pH, cellular transmembrane potentials, and cellular energy metabolism during shock and during ischemia.", "content": "The relevance of two direct techniques for monitoring of cellular function during tissue hypoxia has been evaluated. Tissue pH and cellular transmembrane potentials were registered in canine skeletal muscle during intestinal exteriorization shock and during prolonged local tourniquet ischemia. The obtained pH and transmembrane potential changes were correlated to simultaneous changes in high-energy phosphagen (ATP + CP) and lactate levels in skeletal muscle. In control dogs no significant changes in either of the studied variables occurred. Intestinal exteriorization shock as well as local tourniquet ischemia resulted in a gradual increase in tissue lactate and a concomitant decrease in tissue pH and transmembrane potentials. In both experimental situations there was a close correlation between the transmembrane potential reduction and the tissue lactate increase. Tissue pH registrations, on the other hand, did not similarly reveal the full extent of the tissue lactate increase under the two experimental conditions. Possible reasons for this discrepancy are discussed. On the basis of the present results it may therefore be concluded that the transmembrane potential seems to be a better variable for revealing the full extent of cellular metabolic deterioration during various situations with tissue hypoxia.", "contents": "Correlation between tissue pH, cellular transmembrane potentials, and cellular energy metabolism during shock and during ischemia. The relevance of two direct techniques for monitoring of cellular function during tissue hypoxia has been evaluated. Tissue pH and cellular transmembrane potentials were registered in canine skeletal muscle during intestinal exteriorization shock and during prolonged local tourniquet ischemia. The obtained pH and transmembrane potential changes were correlated to simultaneous changes in high-energy phosphagen (ATP + CP) and lactate levels in skeletal muscle. In control dogs no significant changes in either of the studied variables occurred. Intestinal exteriorization shock as well as local tourniquet ischemia resulted in a gradual increase in tissue lactate and a concomitant decrease in tissue pH and transmembrane potentials. In both experimental situations there was a close correlation between the transmembrane potential reduction and the tissue lactate increase. Tissue pH registrations, on the other hand, did not similarly reveal the full extent of the tissue lactate increase under the two experimental conditions. Possible reasons for this discrepancy are discussed. On the basis of the present results it may therefore be concluded that the transmembrane potential seems to be a better variable for revealing the full extent of cellular metabolic deterioration during various situations with tissue hypoxia."}
{"id": "PMID:30545", "title": "Chemical characteristics of a high molecular weight renin from the renal cortex of the dog.", "content": "We found an acid extract of normal dog kidneys to contain two distinct molecular weight forms of renin-like activity. Gel filtration chromatography showed peaks of activity as estimated molecular weights of 65,000 and 41,000. The high molecular weight fraction (HMW) comprised only 1% of the total activity of the extract. Both HMW and low molecular weight (LMW) fractions were inhibited by anti-human renin antibody and had similar broad pH-dependent activity optima between pH 6.0 and 7.5 in homologous substrate. The Michaelis constant (Km) of HMW was 3.6 times the Km of LMW. Both renins bound reversibly to concanavalin A-Sepharose with comparable affinities. HMW and LMW eluted from DEAE-Sephadex at similar salt concentrations without conversion of HMW to LMW. Transient acidification effected partial conversion of HMW to LMW without changing the total activity. Preincubation of HMW with trypsin increased the activity 40% and effected complete conversion of HMW to LMW. The apparent molecular weight difference between HMW and LMW is probably due to a covalently bound fragment(s) and not to a noncovalently bound moiety such as has been described in the rabbit and the hog. Both HMW and LMW are glycoproteins whose terminal sugar constituents possibly are similar. HMW dog renin is a new molecular form of renin that is convertible to a more active lower molecular weight renin with tryptic proteolysis.", "contents": "Chemical characteristics of a high molecular weight renin from the renal cortex of the dog. We found an acid extract of normal dog kidneys to contain two distinct molecular weight forms of renin-like activity. Gel filtration chromatography showed peaks of activity as estimated molecular weights of 65,000 and 41,000. The high molecular weight fraction (HMW) comprised only 1% of the total activity of the extract. Both HMW and low molecular weight (LMW) fractions were inhibited by anti-human renin antibody and had similar broad pH-dependent activity optima between pH 6.0 and 7.5 in homologous substrate. The Michaelis constant (Km) of HMW was 3.6 times the Km of LMW. Both renins bound reversibly to concanavalin A-Sepharose with comparable affinities. HMW and LMW eluted from DEAE-Sephadex at similar salt concentrations without conversion of HMW to LMW. Transient acidification effected partial conversion of HMW to LMW without changing the total activity. Preincubation of HMW with trypsin increased the activity 40% and effected complete conversion of HMW to LMW. The apparent molecular weight difference between HMW and LMW is probably due to a covalently bound fragment(s) and not to a noncovalently bound moiety such as has been described in the rabbit and the hog. Both HMW and LMW are glycoproteins whose terminal sugar constituents possibly are similar. HMW dog renin is a new molecular form of renin that is convertible to a more active lower molecular weight renin with tryptic proteolysis."}
{"id": "PMID:30546", "title": "Treatment of chronic idiopathic urticaria with combined H1 and H2 blockers.", "content": "Combined H1 (cyproheptadine) and H2 antihistamines (cimetidine) were tried in eight patients with chronic urticaria who were previously unresponsive to conventional anti-urticarial regimens, including type I antihistamines, hydroxyzine, ephedrine and corticosteroids. 50% of the patients responded with 90% or greater improvement within 10 days. The remaining 50% showed no benefit. Side effects of the medications were minimal. These results indicate that a 10 day trial of both H1 and H2 antihistamines may be useful in patients with chronic urticaria resistant to all other standard treatment modalities.", "contents": "Treatment of chronic idiopathic urticaria with combined H1 and H2 blockers. Combined H1 (cyproheptadine) and H2 antihistamines (cimetidine) were tried in eight patients with chronic urticaria who were previously unresponsive to conventional anti-urticarial regimens, including type I antihistamines, hydroxyzine, ephedrine and corticosteroids. 50% of the patients responded with 90% or greater improvement within 10 days. The remaining 50% showed no benefit. Side effects of the medications were minimal. These results indicate that a 10 day trial of both H1 and H2 antihistamines may be useful in patients with chronic urticaria resistant to all other standard treatment modalities."}
{"id": "PMID:30547", "title": "Specific method for serum creatinine determination based on ion exchange chromatography and an automated alkaline picrate reaction -- a proposed reference method.", "content": "A proposed reference method for serum creatinine has been developed under the auspices of the Committee on Reference Methods and Reference Materials of the Canadian Society of Clinical Chemists. A serum ultrafiltrate at pH 2.0 is applied through a closed sample loop injection system to a short column containing cationic resin of high resolving power. Elution with sodium citrate buffer by means of minipump at constant rate passes the eluate into alkaline picrate reagents in a continuous flow system (Technicon AAIII pump, AAII colorimeter 50 mm x 1.5 mm flow cell, narrow band width filter). The colour reaction peak is monitored visually to verify specificity and the area is calculated electronically. Specificity has been demonstrated by use of Jaff\u00e9-reactive substances such as glucose, sodium acetoacetate, L-ascorbic acid, pyruvic acid, L-dopa and glycocyamidine and also by use of an alternate colour reaction, sodium 3,5-dinitrobenzoate in place of alkaline picrate in the analysis of serum pools. Routine methods in common use, i.e., manual and automated alkaline picrate procedures, demonstrated a statistically significant high bias in interlaboratory studies in which this procedure was used for reference.", "contents": "Specific method for serum creatinine determination based on ion exchange chromatography and an automated alkaline picrate reaction -- a proposed reference method. A proposed reference method for serum creatinine has been developed under the auspices of the Committee on Reference Methods and Reference Materials of the Canadian Society of Clinical Chemists. A serum ultrafiltrate at pH 2.0 is applied through a closed sample loop injection system to a short column containing cationic resin of high resolving power. Elution with sodium citrate buffer by means of minipump at constant rate passes the eluate into alkaline picrate reagents in a continuous flow system (Technicon AAIII pump, AAII colorimeter 50 mm x 1.5 mm flow cell, narrow band width filter). The colour reaction peak is monitored visually to verify specificity and the area is calculated electronically. Specificity has been demonstrated by use of Jaff\u00e9-reactive substances such as glucose, sodium acetoacetate, L-ascorbic acid, pyruvic acid, L-dopa and glycocyamidine and also by use of an alternate colour reaction, sodium 3,5-dinitrobenzoate in place of alkaline picrate in the analysis of serum pools. Routine methods in common use, i.e., manual and automated alkaline picrate procedures, demonstrated a statistically significant high bias in interlaboratory studies in which this procedure was used for reference."}
{"id": "PMID:30549", "title": "Multiple molecular forms of certain lysosomal enzymes separated by isoelectric focusing on cellulose acetate membranes.", "content": "Analytical isoelectric focusing on cellulose acetate membranes offers greater resolution of the enzyme pattern than does standard electrophoresis and offers numerous advantages over other support media in isoelectric focusing. A series of lysosomal enzymes, deficiencies of which cause lethal storage diseases in infants and children, can be shown to exist as multiple molecular forms by analytical isoelectrical focusing on cellulose acetate membranes. This analytical technique should be a valuable tool in the investigation of enzyme polymorphism and genetically determined enzyme deficiency diseases.", "contents": "Multiple molecular forms of certain lysosomal enzymes separated by isoelectric focusing on cellulose acetate membranes. Analytical isoelectric focusing on cellulose acetate membranes offers greater resolution of the enzyme pattern than does standard electrophoresis and offers numerous advantages over other support media in isoelectric focusing. A series of lysosomal enzymes, deficiencies of which cause lethal storage diseases in infants and children, can be shown to exist as multiple molecular forms by analytical isoelectrical focusing on cellulose acetate membranes. This analytical technique should be a valuable tool in the investigation of enzyme polymorphism and genetically determined enzyme deficiency diseases."}
{"id": "PMID:30550", "title": "Measurement of serum thyroxine-binding capacity.", "content": "A new method for free thyroxine-binding sites on thyroxine-binding globulin has been described. This method for thyroxine-binding capacity has the virtues of reasonable specificity and convenience for routine use. When used with serum thyroxine levels it should be valuable in the calculation of free thyroxine and total thyroxine-binding globulin. A more directly estimated TBC as reported here should have more value than the various and more empirical T3 uptake methods.", "contents": "Measurement of serum thyroxine-binding capacity. A new method for free thyroxine-binding sites on thyroxine-binding globulin has been described. This method for thyroxine-binding capacity has the virtues of reasonable specificity and convenience for routine use. When used with serum thyroxine levels it should be valuable in the calculation of free thyroxine and total thyroxine-binding globulin. A more directly estimated TBC as reported here should have more value than the various and more empirical T3 uptake methods."}
{"id": "PMID:30551", "title": "A new automated method for the determination of true creatinine in serum by means of the centrifichem centrifugal analyzer, based on Slot's principle; with special reference to low substrate concentrations.", "content": "A new automated method is proposed for the accurate determination of the true creatinine concentration in 20 microliter serum, based on the measurement of the initial rate of the decomposition reaction of the creatinine picrate complex caused by decreasing the pH. The results of this method, performed with a Centrifichem centrifugal analyzer system (type 300 F), are compared with the results obtained by two other methods: a manual method based upon the adsorption on Fuller's earth, and the Auto Analyzer method. In these comparative studies special attention is paid to the analysis of sera containing low (normal) substrate concentrations. Calculation of the orthogonal regression between the results obtained by the adsorption method (x) and the proposed method (y) gave: y=0.97x +/- 5 mumol/l (x=91.3 mumol/l, y-93.5 mumol/l), while for the correlation coefficient (r) 0.9721 was found. All sera (n=113) had creatinine concentrations between 40 and 180 mumol/l.", "contents": "A new automated method for the determination of true creatinine in serum by means of the centrifichem centrifugal analyzer, based on Slot's principle; with special reference to low substrate concentrations. A new automated method is proposed for the accurate determination of the true creatinine concentration in 20 microliter serum, based on the measurement of the initial rate of the decomposition reaction of the creatinine picrate complex caused by decreasing the pH. The results of this method, performed with a Centrifichem centrifugal analyzer system (type 300 F), are compared with the results obtained by two other methods: a manual method based upon the adsorption on Fuller's earth, and the Auto Analyzer method. In these comparative studies special attention is paid to the analysis of sera containing low (normal) substrate concentrations. Calculation of the orthogonal regression between the results obtained by the adsorption method (x) and the proposed method (y) gave: y=0.97x +/- 5 mumol/l (x=91.3 mumol/l, y-93.5 mumol/l), while for the correlation coefficient (r) 0.9721 was found. All sera (n=113) had creatinine concentrations between 40 and 180 mumol/l."}
{"id": "PMID:30552", "title": "Angiotensin I-converting enzyme in human urine.", "content": "It was demonstrated that angiotensin I-converting enzyme was excreted in human urine. The mean activity of the enzyme in normal urine was found to be 0.38 +/- 0.04 (S.E.M.) units/day (n = 18) and the enzymic activity correlated well with the concentration of the excreted sodium (r = 0.76, p less than 0.005). Urinary angiotensin I-converting enzyme was partially purified. Three different molecular weights of enzyme (greater than 400 000, 290 000 and 140 000) were demonstrated by Sephadex G-200 gel filtration. The enzymic properties of these three enzymes were identical with those of angiotensin I-converting enzyme from human lung with regard to inhibitory effects (bradykinin potentiator c and Arg-Pro-Pro), Cl- dependency, pH optimum and KM value.", "contents": "Angiotensin I-converting enzyme in human urine. It was demonstrated that angiotensin I-converting enzyme was excreted in human urine. The mean activity of the enzyme in normal urine was found to be 0.38 +/- 0.04 (S.E.M.) units/day (n = 18) and the enzymic activity correlated well with the concentration of the excreted sodium (r = 0.76, p less than 0.005). Urinary angiotensin I-converting enzyme was partially purified. Three different molecular weights of enzyme (greater than 400 000, 290 000 and 140 000) were demonstrated by Sephadex G-200 gel filtration. The enzymic properties of these three enzymes were identical with those of angiotensin I-converting enzyme from human lung with regard to inhibitory effects (bradykinin potentiator c and Arg-Pro-Pro), Cl- dependency, pH optimum and KM value."}
{"id": "PMID:30554", "title": "The effect of bile on the crystallisation of calcium carbonate, a constituent of gallstones.", "content": "When calcium and bicarbonate ions were mixed at room temperature (approximately 20 degrees C) to give concentrations of 4 mmol/1 and 21 mmol/1 respectively and the pH of the solution was kept at 8.3, vaterite, a form of calcium carbonate, was precipitated almost immediately as spheres of diameter 45 micron. The crystallisation of this material could be slowed down by adding to the crystallising medium small amounts of pyrophosphate or citrate which often inhibit crystal growth. High concentrations of sodium chloride (90 mmol/1) did not, however, affect the reaction. Very small amounts of gallbladder bile from patients with only cholesterol on the surface of their gallstones inhibited the crystallisation of calcium carbonate, and the size of the spheres was only 0.37 times those produced in water. The activity of the bile could be attributed to material with a molecular weight greater than 10 000. On the other hand, bile from patients having some calcium carbonate on the gallstone surface had less activity than comparable amounts of bile from patients with only cholesterol in this area. The active material may, therefore, play a part in preventing the deposition of calcium carbonate in gallstones.", "contents": "The effect of bile on the crystallisation of calcium carbonate, a constituent of gallstones. When calcium and bicarbonate ions were mixed at room temperature (approximately 20 degrees C) to give concentrations of 4 mmol/1 and 21 mmol/1 respectively and the pH of the solution was kept at 8.3, vaterite, a form of calcium carbonate, was precipitated almost immediately as spheres of diameter 45 micron. The crystallisation of this material could be slowed down by adding to the crystallising medium small amounts of pyrophosphate or citrate which often inhibit crystal growth. High concentrations of sodium chloride (90 mmol/1) did not, however, affect the reaction. Very small amounts of gallbladder bile from patients with only cholesterol on the surface of their gallstones inhibited the crystallisation of calcium carbonate, and the size of the spheres was only 0.37 times those produced in water. The activity of the bile could be attributed to material with a molecular weight greater than 10 000. On the other hand, bile from patients having some calcium carbonate on the gallstone surface had less activity than comparable amounts of bile from patients with only cholesterol in this area. The active material may, therefore, play a part in preventing the deposition of calcium carbonate in gallstones."}
{"id": "PMID:30555", "title": "Determination of blood ionized calcium in a large segment of the normal adult population.", "content": "In two different laboratories ionized calcium was determined by use of a calcium selective electrode system of recent design in specimens of whole blood drawn from a total of 100 volunteers. Identical mean values were obtained in each laboratory. A small standard deviation was found supporting the view that [Ca2+] is normally maintained within a narrow range. Ancillary factors in [Ca2+] determination were evaluated, including effects of in-vivo produced changes in pH, and effects of addition of small amounts of heparin to the whole blood sample. A veno-arterial difference in [Ca2+] was insignificant.", "contents": "Determination of blood ionized calcium in a large segment of the normal adult population. In two different laboratories ionized calcium was determined by use of a calcium selective electrode system of recent design in specimens of whole blood drawn from a total of 100 volunteers. Identical mean values were obtained in each laboratory. A small standard deviation was found supporting the view that [Ca2+] is normally maintained within a narrow range. Ancillary factors in [Ca2+] determination were evaluated, including effects of in-vivo produced changes in pH, and effects of addition of small amounts of heparin to the whole blood sample. A veno-arterial difference in [Ca2+] was insignificant."}
{"id": "PMID:30556", "title": "Neuroendocrine control of prolactin in experimental animals.", "content": "Hypothalamic regulation of prolactin secretion in animals (mammals) and man appears to be similar, and no significant differences have yet been demonstrated. The hypothalamus contains neurotransmitters and polypeptides that can either inhibit or stimulate prolactin release, although the predominant influence under basal conditions is to inhibit prolactin release. Thus pituitary stalk section or placement of lesions in the basal tuberal region of the hypothalamus results in increased prolactin release and sometimes in initiation of lactation. Among agents in the hypothalamus that can inhibit prolactin release, the most important appear to be an as yet unidentified polypeptide prolactin release inhibiting factor (PIF) and dopamine. There is some evidence that dopamine may account for most, if not all, of the prolactin release inhibiting activity of the hypothalamus. Agents that increase dopamine activity, i.e. L-dopa, monoamine oxidase inhibitors, etc., depress prolactin release. Acetylcholine also can inhibit prolactin release, but it appears to act via the catecholamines. Of the agents in the hypothalamus that stimulate prolactin release, the most important appear to be an as yet uncharacterized polypeptide prolactin releasing factor (PRF), thyrotropin releasing hormone (TRH) and serotonin. TRH is as effective in releasing prolactin as in releasing TSH, but under most physiological states, TSH and prolactin release do not occur together. Serotonin and its precursors, tryptophan and 5-hydroxytryptophan, are powerful releasors of prolactin and have been shown to be involved in some physiological states in which prolactin is released, i.e. during suckling, stress, etc. Other agents in the hypothalamus that can stimulate prolactin release include GABA and some prostaglandins, but these have not yet been shown to be involved in physiological control of prolactin secretion. Exteroceptive stimuli that alter prolactin release act through the CNS and hypothalamus, but some hormones and drugs also can act directly on the pituitary to promote or depress prolactin release.", "contents": "Neuroendocrine control of prolactin in experimental animals. Hypothalamic regulation of prolactin secretion in animals (mammals) and man appears to be similar, and no significant differences have yet been demonstrated. The hypothalamus contains neurotransmitters and polypeptides that can either inhibit or stimulate prolactin release, although the predominant influence under basal conditions is to inhibit prolactin release. Thus pituitary stalk section or placement of lesions in the basal tuberal region of the hypothalamus results in increased prolactin release and sometimes in initiation of lactation. Among agents in the hypothalamus that can inhibit prolactin release, the most important appear to be an as yet unidentified polypeptide prolactin release inhibiting factor (PIF) and dopamine. There is some evidence that dopamine may account for most, if not all, of the prolactin release inhibiting activity of the hypothalamus. Agents that increase dopamine activity, i.e. L-dopa, monoamine oxidase inhibitors, etc., depress prolactin release. Acetylcholine also can inhibit prolactin release, but it appears to act via the catecholamines. Of the agents in the hypothalamus that stimulate prolactin release, the most important appear to be an as yet uncharacterized polypeptide prolactin releasing factor (PRF), thyrotropin releasing hormone (TRH) and serotonin. TRH is as effective in releasing prolactin as in releasing TSH, but under most physiological states, TSH and prolactin release do not occur together. Serotonin and its precursors, tryptophan and 5-hydroxytryptophan, are powerful releasors of prolactin and have been shown to be involved in some physiological states in which prolactin is released, i.e. during suckling, stress, etc. Other agents in the hypothalamus that can stimulate prolactin release include GABA and some prostaglandins, but these have not yet been shown to be involved in physiological control of prolactin secretion. Exteroceptive stimuli that alter prolactin release act through the CNS and hypothalamus, but some hormones and drugs also can act directly on the pituitary to promote or depress prolactin release."}
{"id": "PMID:30563", "title": "Serum and urine phosphate during short-term beta-adrenergic blockade in healthy men.", "content": "Treatment of 6 healthy adult men with a beta-blocker, timolol, resulted in a rise in serum phosphate which was maintained for the 5 days of therapy. This rise was accompanied by a transient fall in urine phosphate and a rise in the tubular maximum for phosphate reabsorption per unit glomerular filtration rate (TmPO4/GFR). No change in circulating parathyroid hormone or growth hormone could be demonstrated.", "contents": "Serum and urine phosphate during short-term beta-adrenergic blockade in healthy men. Treatment of 6 healthy adult men with a beta-blocker, timolol, resulted in a rise in serum phosphate which was maintained for the 5 days of therapy. This rise was accompanied by a transient fall in urine phosphate and a rise in the tubular maximum for phosphate reabsorption per unit glomerular filtration rate (TmPO4/GFR). No change in circulating parathyroid hormone or growth hormone could be demonstrated."}
{"id": "PMID:30564", "title": "Physostigmine for cardiac and neurologic manifestations of phenothiazine poisoning.", "content": "Psychotropic drugs such as the phenothiazine neuroleptics and tricyclic antidepressants are known to cause electrocardiographic abnormalities as well as a central anticholinergic syndrome. Physostigmine is known to reverse the central muscarinic anticholinergic manifestations by inhibition of the enzyme cholinesterase. An unusual case of trifluoperazine overdose, in which the patient presented with cardiac arrhythmias and a central anticholinergic syndrome, is presented. Treatment with physostigmine reversed the central anticholinergic syndrome as well as the electrocardiographic abnormalities. Effects of phenothiazines on altering cardiac status are also discussed.", "contents": "Physostigmine for cardiac and neurologic manifestations of phenothiazine poisoning. Psychotropic drugs such as the phenothiazine neuroleptics and tricyclic antidepressants are known to cause electrocardiographic abnormalities as well as a central anticholinergic syndrome. Physostigmine is known to reverse the central muscarinic anticholinergic manifestations by inhibition of the enzyme cholinesterase. An unusual case of trifluoperazine overdose, in which the patient presented with cardiac arrhythmias and a central anticholinergic syndrome, is presented. Treatment with physostigmine reversed the central anticholinergic syndrome as well as the electrocardiographic abnormalities. Effects of phenothiazines on altering cardiac status are also discussed."}
{"id": "PMID:30596", "title": "Parenteral treatment of acute psychotic patients with agitation: a review.", "content": "Representative studies which elucidate present treatment principles regarding parenteral administration of neuroleptics for acute psychoses with agitation are reviewed. \"Rapid tranquillization\" with drugs such as haloperidol generally appears preferable, but controlled comparisons with more conservative types of treatment are lacking. It is suggested that parenteral chlorpromazine should be avoided because of its tendency to provoke severe hypotension, whereas loxapine apparently is a valuable drug if strong sedation is required for behavioural control. Possible advantages of ultra-high-dose therapy need to be proved in controlled trials, and the occurrence of toxic side-effects requires further evaluation. From an ethical and psychological point of view, it is recommended that antiparkinsonian medication should be administered simultaneously with neuroleptics which induce a high incidence of acute dystonia. Several types of acute psychosis with agitation which do not require treatment with a neuroleptic as drug treatment of first choice are briefly mentioned.", "contents": "Parenteral treatment of acute psychotic patients with agitation: a review. Representative studies which elucidate present treatment principles regarding parenteral administration of neuroleptics for acute psychoses with agitation are reviewed. \"Rapid tranquillization\" with drugs such as haloperidol generally appears preferable, but controlled comparisons with more conservative types of treatment are lacking. It is suggested that parenteral chlorpromazine should be avoided because of its tendency to provoke severe hypotension, whereas loxapine apparently is a valuable drug if strong sedation is required for behavioural control. Possible advantages of ultra-high-dose therapy need to be proved in controlled trials, and the occurrence of toxic side-effects requires further evaluation. From an ethical and psychological point of view, it is recommended that antiparkinsonian medication should be administered simultaneously with neuroleptics which induce a high incidence of acute dystonia. Several types of acute psychosis with agitation which do not require treatment with a neuroleptic as drug treatment of first choice are briefly mentioned."}
{"id": "PMID:30597", "title": "Intramuscular/oral lorazepam in acute alcohol withdrawal and incipient delirium tremens.", "content": "An open study was carried out in 21 chronic alcoholics with severe withdrawal symptoms and incipient delirium tremens to evaluate the efficacy of adjuvant treatment with intramuscular lorazepam (5mg). All symptoms subsided within 2 hours after a single injection and remained under control with oral lorazepam (mean daily dose 7 mg). No adverse reactions attributable to lorazepam were observed.", "contents": "Intramuscular/oral lorazepam in acute alcohol withdrawal and incipient delirium tremens. An open study was carried out in 21 chronic alcoholics with severe withdrawal symptoms and incipient delirium tremens to evaluate the efficacy of adjuvant treatment with intramuscular lorazepam (5mg). All symptoms subsided within 2 hours after a single injection and remained under control with oral lorazepam (mean daily dose 7 mg). No adverse reactions attributable to lorazepam were observed."}
{"id": "PMID:30598", "title": "The use of a kymograph in a comparative trial of flunitrazepam and meprobamate in elderly patients.", "content": "A double-blind crossover trial was carried out in 31 hospitalized elderly patients receiving night-time sedation to compare the effects of flunitrazepam (0.5 mg) and meprobamate (200 mg). After 1 week on placebo, patients received 1-week's treatment with each drug in random order. Quality of sleep was assessed by a nurse at hourly intervals over 8 hours each night. In 11 patients, the results were compared with those from kymographic recordings measuring patient restlessness (motility index). No statistically significant difference was found between the two active drug treatments, and there was a close correlation between the two methods of assessment. It is suggested that the kymograph may well be a useful and economic method of evaluating the effectiveness of hypnotics.", "contents": "The use of a kymograph in a comparative trial of flunitrazepam and meprobamate in elderly patients. A double-blind crossover trial was carried out in 31 hospitalized elderly patients receiving night-time sedation to compare the effects of flunitrazepam (0.5 mg) and meprobamate (200 mg). After 1 week on placebo, patients received 1-week's treatment with each drug in random order. Quality of sleep was assessed by a nurse at hourly intervals over 8 hours each night. In 11 patients, the results were compared with those from kymographic recordings measuring patient restlessness (motility index). No statistically significant difference was found between the two active drug treatments, and there was a close correlation between the two methods of assessment. It is suggested that the kymograph may well be a useful and economic method of evaluating the effectiveness of hypnotics."}
{"id": "PMID:30599", "title": "3,4,5-Trimethoxybenzoic acid, a new mescaline metabolite in humans.", "content": "After ingestion of 400 mg of mescaline sulfate by human volunteers, 3,4,5-trimethoxybenzoic acid was isolated from urine and identified by gas chromatography-mass spectrometry. The amount of this anionic mescaline metabolite was found to be very low as compared with that of the well-konwn 3,4,5-trimethoxyphenylacetic acid. The significance of this finding is discussed.", "contents": "3,4,5-Trimethoxybenzoic acid, a new mescaline metabolite in humans. After ingestion of 400 mg of mescaline sulfate by human volunteers, 3,4,5-trimethoxybenzoic acid was isolated from urine and identified by gas chromatography-mass spectrometry. The amount of this anionic mescaline metabolite was found to be very low as compared with that of the well-konwn 3,4,5-trimethoxyphenylacetic acid. The significance of this finding is discussed."}
{"id": "PMID:30600", "title": "Species differences in the disposition and metabolism of 6,11-dihydro-11-oxodibenz[be]oxepin-2-acetic acid (isoxepac) in rat, rabbit, dog, rhesus monkey, and man.", "content": "The disposition and metabolism of 6,11-dihydro-11-oxodibenz[be]oxepin-2-acetic acid (isoxepac), a new nonsteroidal anti-inflammatory agent, has been studied in rat, rabbit, dog, rhesus monkey, and man. Animals were given single oral or parenteral doses of 5 or 50 mg/kg; man received approximately 3 mg/kg orally. Fecal excretion of radioactivity occurred in the rat (26--37%) and dog (33--49%), whereas in the other species elimination was mainly urinary (less than 83%). Biliary excretion accounted for 18--52% of the dose in the rat and dog. Enterohepatic circulation was demonstrated in both species. Plasma of all species was found to contain mainly unchanged isoxepac. The compound was rapidly eliminated from plasma of dog, rhesus monkey and man, but was more slowly eliminated in rat and rabbit. In the rabbit and dog the principal metabolites were the glycine and taurine conjugates of isoxepac, respectively, whereas in the rhesus monkey and man, isoxepac was excreted unchanged or as the glucuronide.", "contents": "Species differences in the disposition and metabolism of 6,11-dihydro-11-oxodibenz[be]oxepin-2-acetic acid (isoxepac) in rat, rabbit, dog, rhesus monkey, and man. The disposition and metabolism of 6,11-dihydro-11-oxodibenz[be]oxepin-2-acetic acid (isoxepac), a new nonsteroidal anti-inflammatory agent, has been studied in rat, rabbit, dog, rhesus monkey, and man. Animals were given single oral or parenteral doses of 5 or 50 mg/kg; man received approximately 3 mg/kg orally. Fecal excretion of radioactivity occurred in the rat (26--37%) and dog (33--49%), whereas in the other species elimination was mainly urinary (less than 83%). Biliary excretion accounted for 18--52% of the dose in the rat and dog. Enterohepatic circulation was demonstrated in both species. Plasma of all species was found to contain mainly unchanged isoxepac. The compound was rapidly eliminated from plasma of dog, rhesus monkey and man, but was more slowly eliminated in rat and rabbit. In the rabbit and dog the principal metabolites were the glycine and taurine conjugates of isoxepac, respectively, whereas in the rhesus monkey and man, isoxepac was excreted unchanged or as the glucuronide."}
{"id": "PMID:30602", "title": "Comparative physiological disposition of ellipticine in several animal species after intravenous administration.", "content": "The physiological dispositon of ellipticine (NSC 71795) has been studied in the mouse, rat, dog and monkey after administration of [1-14C]ellipticine at 6 mg/kg iv (3 mg/kg to monkey). Ellipticine was very rapidly distributed from the blood of all species and was deposited in tissues. The rate of elimination of ellipticine from blood was species-dependent, half-times ranging from 22 min in mouse to 210 min in rat, and probably reflected the rate of metabolism of the drug. The rate of elimination of metabolites from blood was also species-dependent, half-times ranging from 140 min in mouse to 380 min in rat, and probably reflected the rate of biliary secretion of the metabolites. Ellipticine was widely but not uniformly distributed throughout the tissues including brain, and some of the highest concentrations of drug and metabolites were in liver, which is probably the primary site of metabolism. The concentrations of ellipticine and metabolites in tissues were species-dependent, correlating with species differences in rates of metabolism and excretion. All species excreted 80% of the dose via the fecal route and 10% via the urinary route, primarily as metabolites during the first 24 hr after dosing. Metabolites entered the gastrointestinal tract by biliary secretion and ellipticine entered by an ion-trapping mechanism. Evidence is presented that the major pathway for ellipticine metabolism in rat was to 9-hydroxyellipticine, which did not accumulate in liver but was conjugated to its glucuronide and sulfate, which were secreted in bile. Other pathways involved hydroxylation and glucuronide conjugation. The pharmacokinetics of ellipticine are correlated with its toxic side effects, such as acute hypotention and neurological symptoms. They are also correlated with its potential as an antitumor agent, such as its ability to achieve values for the area under the curve of concentration vs. time (CXt) in tumors, which would be adequate for therapy. Based upon these correlations, the drug should be administered in the clinic by iv infusion, or, provided its bioavailability is found to be satisfactory, by the oral route.", "contents": "Comparative physiological disposition of ellipticine in several animal species after intravenous administration. The physiological dispositon of ellipticine (NSC 71795) has been studied in the mouse, rat, dog and monkey after administration of [1-14C]ellipticine at 6 mg/kg iv (3 mg/kg to monkey). Ellipticine was very rapidly distributed from the blood of all species and was deposited in tissues. The rate of elimination of ellipticine from blood was species-dependent, half-times ranging from 22 min in mouse to 210 min in rat, and probably reflected the rate of metabolism of the drug. The rate of elimination of metabolites from blood was also species-dependent, half-times ranging from 140 min in mouse to 380 min in rat, and probably reflected the rate of biliary secretion of the metabolites. Ellipticine was widely but not uniformly distributed throughout the tissues including brain, and some of the highest concentrations of drug and metabolites were in liver, which is probably the primary site of metabolism. The concentrations of ellipticine and metabolites in tissues were species-dependent, correlating with species differences in rates of metabolism and excretion. All species excreted 80% of the dose via the fecal route and 10% via the urinary route, primarily as metabolites during the first 24 hr after dosing. Metabolites entered the gastrointestinal tract by biliary secretion and ellipticine entered by an ion-trapping mechanism. Evidence is presented that the major pathway for ellipticine metabolism in rat was to 9-hydroxyellipticine, which did not accumulate in liver but was conjugated to its glucuronide and sulfate, which were secreted in bile. Other pathways involved hydroxylation and glucuronide conjugation. The pharmacokinetics of ellipticine are correlated with its toxic side effects, such as acute hypotention and neurological symptoms. They are also correlated with its potential as an antitumor agent, such as its ability to achieve values for the area under the curve of concentration vs. time (CXt) in tumors, which would be adequate for therapy. Based upon these correlations, the drug should be administered in the clinic by iv infusion, or, provided its bioavailability is found to be satisfactory, by the oral route."}
{"id": "PMID:30601", "title": "Biotransformation of methyl 5-cyclopropylcarbonyl-2-benzimidazolecarbamate (ciclobendazole) in rats and dogs.", "content": "A major metabolite of ciclobendazole (methyl 5-cyclopropylcarbonyl-2-benzimidazolecarbamate) excreted in the urine, bile, and feces of rats was methyl 5-cyclopropylcarbonyl-6-hydroxy-benzimidazolecarbamate, established by comparison of the proton magnetic resonance and mass spectra with that of the authentic compound. This compound represented 8.2% and 7.1% of the dose, respectively, in extracts of 24-hr urine and 48-hr feces samples of rats, but was only a minor metabolite in dog urine (1% of the dose). The unchanged drug was only detected in dog feces, the major route of excretion of radioactivity in the dog. 5-Cyclopropylcarbonyl-2-amino-benzimidazole was present in rat urine (2.5% of the dose). A major metabolite in dog bile was probably 5-cyclopropylcarbinol-2-aminobenzimidazole, formed by loss of the methoxycarbonyl group and reduction of the carbonyl function in the 5-position.", "contents": "Biotransformation of methyl 5-cyclopropylcarbonyl-2-benzimidazolecarbamate (ciclobendazole) in rats and dogs. A major metabolite of ciclobendazole (methyl 5-cyclopropylcarbonyl-2-benzimidazolecarbamate) excreted in the urine, bile, and feces of rats was methyl 5-cyclopropylcarbonyl-6-hydroxy-benzimidazolecarbamate, established by comparison of the proton magnetic resonance and mass spectra with that of the authentic compound. This compound represented 8.2% and 7.1% of the dose, respectively, in extracts of 24-hr urine and 48-hr feces samples of rats, but was only a minor metabolite in dog urine (1% of the dose). The unchanged drug was only detected in dog feces, the major route of excretion of radioactivity in the dog. 5-Cyclopropylcarbonyl-2-amino-benzimidazole was present in rat urine (2.5% of the dose). A major metabolite in dog bile was probably 5-cyclopropylcarbinol-2-aminobenzimidazole, formed by loss of the methoxycarbonyl group and reduction of the carbonyl function in the 5-position."}
{"id": "PMID:30605", "title": "Metabolism of haloforms to carbon monoxide. II. In vivo studies.", "content": "Administration of haloforms (trihalomethanes) to rats led to substantial elevations in blood carbon monoxide levels. The administration of 13C-bromoform led to the formation of similarly enriched 13CO. A dose-dependent relationship between bromoform dose and CO production was observed. It was found that phenobarbital, but not 3-methylcholanthrene, treatment increased the blood CO levels seen after the administration of bromoform as compared to saline-treated controls. Lower blood CO levels were found in rats given 2H-bromoform as compared to rats given bromoform. Furthermore, SKF 525-A significantly inhibited the in vivo metabolism of bromoform to CO. Administration of either diethyl maleate or D-penicillamine did not alter the blood CO levels produced in response to bromoform administration. The in vivo metabolism of haloforms to CO followed the halide order; thus, administration of iodoform yielded the highest blood CO levels, whereas chloroform yielded the lowest levels.", "contents": "Metabolism of haloforms to carbon monoxide. II. In vivo studies. Administration of haloforms (trihalomethanes) to rats led to substantial elevations in blood carbon monoxide levels. The administration of 13C-bromoform led to the formation of similarly enriched 13CO. A dose-dependent relationship between bromoform dose and CO production was observed. It was found that phenobarbital, but not 3-methylcholanthrene, treatment increased the blood CO levels seen after the administration of bromoform as compared to saline-treated controls. Lower blood CO levels were found in rats given 2H-bromoform as compared to rats given bromoform. Furthermore, SKF 525-A significantly inhibited the in vivo metabolism of bromoform to CO. Administration of either diethyl maleate or D-penicillamine did not alter the blood CO levels produced in response to bromoform administration. The in vivo metabolism of haloforms to CO followed the halide order; thus, administration of iodoform yielded the highest blood CO levels, whereas chloroform yielded the lowest levels."}
{"id": "PMID:30603", "title": "Characterization of the metabolites of ellipticine in rat bile.", "content": "The two major metabolites of ellipticine (NSC 71795) were isolated from rat bile by a combination of solvent extraction, partition column chromatography, and reverse phase high-performance liquid chromatography. Purification and structural elucidation of the bile products were aided by administration of the drug with a dual label (14C and 2H). The two metabolites were shown to be the sulfate and glucuronide conjugates of 9-hydroxyellipticine by chemical, enzymatic, and mass-spectral fragmentation comparison with synthetic and enzymatically prepared reference compounds.", "contents": "Characterization of the metabolites of ellipticine in rat bile. The two major metabolites of ellipticine (NSC 71795) were isolated from rat bile by a combination of solvent extraction, partition column chromatography, and reverse phase high-performance liquid chromatography. Purification and structural elucidation of the bile products were aided by administration of the drug with a dual label (14C and 2H). The two metabolites were shown to be the sulfate and glucuronide conjugates of 9-hydroxyellipticine by chemical, enzymatic, and mass-spectral fragmentation comparison with synthetic and enzymatically prepared reference compounds."}
{"id": "PMID:30607", "title": "Complications in the estimation of hepatic blood flow in vivo by pharmacokinetic parameters. The area under the curve after the concomitant intravenous and intraperitoneal (or intraportal) administration of acetaminophen in the rat.", "content": "Hepatic blood flow can be estimated from the area under the blood or plasma concentration-time curve of a drug following an intravenous dose and either an oral or intraperitoneal dose. The validity of the method depends on several factors which alter the area under the curve, that is, hemodynamic interactions due to the drug or its metabolites, the use of plasma concentration as opposed to blood concentration data, incomplete absorption on oral or intraperitoneal administration, enterohepatic recycling of the drug or its metabolite, and the presence of extrahepatic metabolism. The validity of the method was tested in rats with tracer doses of acetaminophen. After the simultaneous administration of an iv dose of 14C-acetaminophen and an intraportal dose of 3H-acetaminophen to rats, the availability after the first-pass hepatic extraction of acetaminophen in rats was 0.56 +/- 0.05. Hepatic blood flow estimated by the area under the curve for the respective routes of administration was 78.1 +/- 16.1 ml/min/kg. However, after the simultaneous administration of an iv tracer dose of 14C-acetaminophen and an ip dose of 3H-acetaminophen, the apparent availabilities calculated from the areas under the curve were highly variable and tended to be greater (0.73 +/- 0.11). Thus the estimates of the hepatic blood flow also tended to be higher (159 +/- 65 ml/min/kg).", "contents": "Complications in the estimation of hepatic blood flow in vivo by pharmacokinetic parameters. The area under the curve after the concomitant intravenous and intraperitoneal (or intraportal) administration of acetaminophen in the rat. Hepatic blood flow can be estimated from the area under the blood or plasma concentration-time curve of a drug following an intravenous dose and either an oral or intraperitoneal dose. The validity of the method depends on several factors which alter the area under the curve, that is, hemodynamic interactions due to the drug or its metabolites, the use of plasma concentration as opposed to blood concentration data, incomplete absorption on oral or intraperitoneal administration, enterohepatic recycling of the drug or its metabolite, and the presence of extrahepatic metabolism. The validity of the method was tested in rats with tracer doses of acetaminophen. After the simultaneous administration of an iv dose of 14C-acetaminophen and an intraportal dose of 3H-acetaminophen to rats, the availability after the first-pass hepatic extraction of acetaminophen in rats was 0.56 +/- 0.05. Hepatic blood flow estimated by the area under the curve for the respective routes of administration was 78.1 +/- 16.1 ml/min/kg. However, after the simultaneous administration of an iv tracer dose of 14C-acetaminophen and an ip dose of 3H-acetaminophen, the apparent availabilities calculated from the areas under the curve were highly variable and tended to be greater (0.73 +/- 0.11). Thus the estimates of the hepatic blood flow also tended to be higher (159 +/- 65 ml/min/kg)."}
{"id": "PMID:30613", "title": "[Drug prevention of bronchial asthma: inhibition of histamine and exercise-induced asthma by a new anti-anaphylactic oral preparation (ketotifen) (author's transl)].", "content": "The protective anti-asthmatic effect of a new anti-allergic drug with histaminolytic and anti-anaphylactic properties was tested in various controlled clinical studies of induced bronchospasm in asthmatic patients (provocation tests using a histamine aerosol, and exercise-induced asthma using a bicycle ergometer). The drug, ketotifen (a cycloheptathiophene derivative) was compared with a classical antihistaminic (clemastine) and a known cell stabiliser (disodium cromoglycate). In both models ketotifen provided significant protection.", "contents": "[Drug prevention of bronchial asthma: inhibition of histamine and exercise-induced asthma by a new anti-anaphylactic oral preparation (ketotifen) (author's transl)]. The protective anti-asthmatic effect of a new anti-allergic drug with histaminolytic and anti-anaphylactic properties was tested in various controlled clinical studies of induced bronchospasm in asthmatic patients (provocation tests using a histamine aerosol, and exercise-induced asthma using a bicycle ergometer). The drug, ketotifen (a cycloheptathiophene derivative) was compared with a classical antihistaminic (clemastine) and a known cell stabiliser (disodium cromoglycate). In both models ketotifen provided significant protection."}
{"id": "PMID:30606", "title": "Factors affecting the metabolism of [14C]acetylhydrazine in rats.", "content": "Some factors affecting the metabolism of the potent hepatotoxin, acetylhydrazine, were studied in rats. After ip administration of [14C]acetylhydrazine, 36% and 38% of the dose was recovered in the urine and as 14CO2, respectively. The major urinary metabolites were diacetylhydrazine and the pyruvic acid and alpha-oxoglutaric acid acetylhydrazones. The acetylation of acetylhydrazine to diacetylhydrazine was found to be dose-dependent and to be inhibited by coadministered isoniazid and p-aminosalicylic acid. Coadministered acetylisoniazid had no effect on acetylation. The proportion of acetylhydrazine recovered as 14CO2 presumably reflects the amount metabolized by the microsomal oxidation pathway, thought to be responsible for the toxicity, and also possibly by hydrolysis to acetate and hydrazine. This latter pathway could not be confirmed, as only a small proportion of hydrazine administered to rats was recovered. The inhibition of acetylation by p-aminosalicyclic acid, but not isoniazid, significantly increased the excretion of 14CO2, suggesting that isoniazid may also inhibit a pathway resulting in the production of 14CO2. These results indicate that the metabolism and hepatotoxicity of acetylhydrazine may be different when it is produced as a metabolite of isoniazid than when it is given alone.", "contents": "Factors affecting the metabolism of [14C]acetylhydrazine in rats. Some factors affecting the metabolism of the potent hepatotoxin, acetylhydrazine, were studied in rats. After ip administration of [14C]acetylhydrazine, 36% and 38% of the dose was recovered in the urine and as 14CO2, respectively. The major urinary metabolites were diacetylhydrazine and the pyruvic acid and alpha-oxoglutaric acid acetylhydrazones. The acetylation of acetylhydrazine to diacetylhydrazine was found to be dose-dependent and to be inhibited by coadministered isoniazid and p-aminosalicylic acid. Coadministered acetylisoniazid had no effect on acetylation. The proportion of acetylhydrazine recovered as 14CO2 presumably reflects the amount metabolized by the microsomal oxidation pathway, thought to be responsible for the toxicity, and also possibly by hydrolysis to acetate and hydrazine. This latter pathway could not be confirmed, as only a small proportion of hydrazine administered to rats was recovered. The inhibition of acetylation by p-aminosalicyclic acid, but not isoniazid, significantly increased the excretion of 14CO2, suggesting that isoniazid may also inhibit a pathway resulting in the production of 14CO2. These results indicate that the metabolism and hepatotoxicity of acetylhydrazine may be different when it is produced as a metabolite of isoniazid than when it is given alone."}
{"id": "PMID:30610", "title": "Metabolism of methimazole by rat liver cytochrome P-450-containing monoxygenases.", "content": "The incubation of methimazole (1-methyl-2-thioimidazole, MMI) with rat hepatic microsomes led to the formation of 3-methyl-2-thiohydantoin and N-methylimidazole. In addition, an NADPH-stimulated binding of 14C and 35S from [14C]- and [35s]MMI to microsomal macromolecules was seen. Both the NADPH-stimulated N-methylimidazole formation and binding of radioactivity from [14C]- and [35S]MMI to microsomal macromolecules appeared to be catalyzed largely by the cytocrhome P-450 to monoxygenase systems of rat hepatic microsomes. A portion of the radioactivity bound to microsomes incubated with [14C]- and [35S]MMI was released as unchanged MMI on prolonged incubation under acid conditions; this suggests that strong binding of MMI to microsomes occurred. A portion of the 35S bound to microsomes incubated with [35S]MMI can be released as 35SCN- on incubation of the 35S-labeled microsomes with CN-. These data suggest that a portion of the sulfur released in the metabolism of MMI to N-methylimidazole is in the form of atomic sulfur (S), which binds to cysteine sulfhydryl groups (R-S-H) in microsomal proteins to form a hydrodisulfide (R-S-S-H).", "contents": "Metabolism of methimazole by rat liver cytochrome P-450-containing monoxygenases. The incubation of methimazole (1-methyl-2-thioimidazole, MMI) with rat hepatic microsomes led to the formation of 3-methyl-2-thiohydantoin and N-methylimidazole. In addition, an NADPH-stimulated binding of 14C and 35S from [14C]- and [35s]MMI to microsomal macromolecules was seen. Both the NADPH-stimulated N-methylimidazole formation and binding of radioactivity from [14C]- and [35S]MMI to microsomal macromolecules appeared to be catalyzed largely by the cytocrhome P-450 to monoxygenase systems of rat hepatic microsomes. A portion of the radioactivity bound to microsomes incubated with [14C]- and [35S]MMI was released as unchanged MMI on prolonged incubation under acid conditions; this suggests that strong binding of MMI to microsomes occurred. A portion of the 35S bound to microsomes incubated with [35S]MMI can be released as 35SCN- on incubation of the 35S-labeled microsomes with CN-. These data suggest that a portion of the sulfur released in the metabolism of MMI to N-methylimidazole is in the form of atomic sulfur (S), which binds to cysteine sulfhydryl groups (R-S-H) in microsomal proteins to form a hydrodisulfide (R-S-S-H)."}
{"id": "PMID:30616", "title": "[Biochemistry of depression. Literature analysis].", "content": "The author goes briefly over the metabolism of the main cerebral monoamines, the functioning of synapses, as well as the methods used in studying the biochemistry of depression. Beyond all existing contradictory results, a review of the main works in this field enables us to point out some leading ideas:--Depression would be due to and/or accompanied by a monoaminergic deficiency: some authors emphasize the serotonin one, others the noradrenaline one.--The regulation of mood most probably finds its origin in the monoaminergic balance, rather than in the gross rates of any particular monoamine.--Disturbances are to be found on all metabolic levels: monoaminergic, hydroelectrolytic, hormonal, glucidic, lipidic, lipidic... Close intrication exists between those different metabolisms.--The interaction between the different aminergic systems and the metabolic ways, as well as the dispersion of the acknowledged results, impose more and more the necessity of a biochemical typology of depression, which would lead to a predictive approach to the evolution and treatment of depressive illness.", "contents": "[Biochemistry of depression. Literature analysis]. The author goes briefly over the metabolism of the main cerebral monoamines, the functioning of synapses, as well as the methods used in studying the biochemistry of depression. Beyond all existing contradictory results, a review of the main works in this field enables us to point out some leading ideas:--Depression would be due to and/or accompanied by a monoaminergic deficiency: some authors emphasize the serotonin one, others the noradrenaline one.--The regulation of mood most probably finds its origin in the monoaminergic balance, rather than in the gross rates of any particular monoamine.--Disturbances are to be found on all metabolic levels: monoaminergic, hydroelectrolytic, hormonal, glucidic, lipidic, lipidic... Close intrication exists between those different metabolisms.--The interaction between the different aminergic systems and the metabolic ways, as well as the dispersion of the acknowledged results, impose more and more the necessity of a biochemical typology of depression, which would lead to a predictive approach to the evolution and treatment of depressive illness."}
{"id": "PMID:30611", "title": "Partial purification and characterization of dihydropyrimidinases from calf and rat liver.", "content": "The partial purification of rat and calf liver dihydropyrimidinase (EC 3.5.2.2) is described. Molecular weights of the native calf and rat liver enzymes were estimated by gel-filtration chromatography to be 252,000 and 266,000 daltons, respectively. Subunit molecular weights of the calf and rat liver enzyme were estimated by SDS-gel electrophoresis to be 59,000 and 62,000 daltons, respectively. The native enzyme in both species is thought to comprise four subunits. The purified enzyme from both species was capable of catalyzing the hydrolytic ring opening of dihydrouracil, 5-phenylhydantoin, hydantoin, and alpha-phenylsuccinimide.", "contents": "Partial purification and characterization of dihydropyrimidinases from calf and rat liver. The partial purification of rat and calf liver dihydropyrimidinase (EC 3.5.2.2) is described. Molecular weights of the native calf and rat liver enzymes were estimated by gel-filtration chromatography to be 252,000 and 266,000 daltons, respectively. Subunit molecular weights of the calf and rat liver enzyme were estimated by SDS-gel electrophoresis to be 59,000 and 62,000 daltons, respectively. The native enzyme in both species is thought to comprise four subunits. The purified enzyme from both species was capable of catalyzing the hydrolytic ring opening of dihydrouracil, 5-phenylhydantoin, hydantoin, and alpha-phenylsuccinimide."}
{"id": "PMID:30617", "title": "Effects of adrenergic blocking agents on lipolysis and adenyl cyclase activity induced by vasoactive intestinal polypeptide (VIP).", "content": "VIP stimulates lipolysis and adenyl cyclase activity in the rat adipose tissue. VIP-induced lipolysis and adenyl cyclase activity are not affected by phenoxybenzamine. VIP-induced lipolysis is inhibited by propranolol but VIP-induced adenyl cyclase activity is not.", "contents": "Effects of adrenergic blocking agents on lipolysis and adenyl cyclase activity induced by vasoactive intestinal polypeptide (VIP). VIP stimulates lipolysis and adenyl cyclase activity in the rat adipose tissue. VIP-induced lipolysis and adenyl cyclase activity are not affected by phenoxybenzamine. VIP-induced lipolysis is inhibited by propranolol but VIP-induced adenyl cyclase activity is not."}
{"id": "PMID:30619", "title": "Effect of hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine on guanylate cyclase activity.", "content": "The chemical carcinogen hydrazine is a potent stimulator of guanylate cyclase. In the present investigation we found that three chemical carcinogens structurally related to hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine, decreased guanylate cyclase activity. It is of interest that hydrazine has been shown to increase DNA synthesis whereas isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine decrease DNA synthesis. The relationship, if any, linking the guanylate cyclase-cyclic GMP system to DNA synthesis and carcinogenesis remains to be explored.", "contents": "Effect of hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine on guanylate cyclase activity. The chemical carcinogen hydrazine is a potent stimulator of guanylate cyclase. In the present investigation we found that three chemical carcinogens structurally related to hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine, decreased guanylate cyclase activity. It is of interest that hydrazine has been shown to increase DNA synthesis whereas isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine decrease DNA synthesis. The relationship, if any, linking the guanylate cyclase-cyclic GMP system to DNA synthesis and carcinogenesis remains to be explored."}
{"id": "PMID:30620", "title": "Purification and properties of hexoasmine isomerase (EC5.3.1.19) from pig intestinal mucosa.", "content": "Hexosamine isomerase from pig intestinal mucosa was purified about 70-fold. The aminosugar product of the enzymatic reaction was identified as glucosamine 6-phosphate and amino acid product as glutamic acid. The pH optimum was 7.1 Km for fructose 6-phosphate was 6.3 X 10(-4) mol/1 and for L-glutamine 6.5 X 10(-4) mol/1.", "contents": "Purification and properties of hexoasmine isomerase (EC5.3.1.19) from pig intestinal mucosa. Hexosamine isomerase from pig intestinal mucosa was purified about 70-fold. The aminosugar product of the enzymatic reaction was identified as glucosamine 6-phosphate and amino acid product as glutamic acid. The pH optimum was 7.1 Km for fructose 6-phosphate was 6.3 X 10(-4) mol/1 and for L-glutamine 6.5 X 10(-4) mol/1."}
{"id": "PMID:30621", "title": "Modulation of rat guanylate cyclase activity in vitro by chemical carcinogens.", "content": "The nucleotide cyclic GMP has been reported to be involved in cell proliferation and malignant transformation. Nitroso chemical carcinogens activate the enzyme guanylate cyclase (EC 4.6.1.2) which catalyzes the production of cyclic GMP. The present investigation demonstrates that compounds from other major classes of carcinogens including (1) alpha-halo ethers (chloromethyl methyl ether); (2) aromatic amines (benzidine and B-naphthylamine); (3) polycyclic hydrocarbons (1,2-benzanthracene and acridine); (4) azo dyes (p-dimethylaminoazobenzene), and (5) aflatoxins (B1, B2, G1, G2) produced a striking and significant inhibition of guanylate cyclase over a general concentration range of 0.5-13 mmol/1 in a variety of tissues. Some of the nitrosamides which increase guanylate cyclase activity, increase DNA synthesis whereas carcinogens which decrease guanylate cyclase activity inhibit DNA or RNA synthesis suggesting a relationship between cyclic GMP, DNA synthesis, and chemical carcinogenesis.", "contents": "Modulation of rat guanylate cyclase activity in vitro by chemical carcinogens. The nucleotide cyclic GMP has been reported to be involved in cell proliferation and malignant transformation. Nitroso chemical carcinogens activate the enzyme guanylate cyclase (EC 4.6.1.2) which catalyzes the production of cyclic GMP. The present investigation demonstrates that compounds from other major classes of carcinogens including (1) alpha-halo ethers (chloromethyl methyl ether); (2) aromatic amines (benzidine and B-naphthylamine); (3) polycyclic hydrocarbons (1,2-benzanthracene and acridine); (4) azo dyes (p-dimethylaminoazobenzene), and (5) aflatoxins (B1, B2, G1, G2) produced a striking and significant inhibition of guanylate cyclase over a general concentration range of 0.5-13 mmol/1 in a variety of tissues. Some of the nitrosamides which increase guanylate cyclase activity, increase DNA synthesis whereas carcinogens which decrease guanylate cyclase activity inhibit DNA or RNA synthesis suggesting a relationship between cyclic GMP, DNA synthesis, and chemical carcinogenesis."}
{"id": "PMID:30623", "title": "CNS and pituitary effects of hypothalamic peptides and MSH.", "content": "The first part of this essay discussed the CNS effects of the pituitary peptide MSH. These investigations anticipated studies of the CNS effects of peptides found in the hypothalamus which were discussed in the second part of the essay. Some of the endocrine actions of the hypothalamic peptides upon the release of pituitary hormones were discussed in the last part of the essay. Together, the CNS and pituitary effects of hypothalamic peptides and MSH provide intriguing examples of areas of investigation which can be expected to be greatly expanded in the future.", "contents": "CNS and pituitary effects of hypothalamic peptides and MSH. The first part of this essay discussed the CNS effects of the pituitary peptide MSH. These investigations anticipated studies of the CNS effects of peptides found in the hypothalamus which were discussed in the second part of the essay. Some of the endocrine actions of the hypothalamic peptides upon the release of pituitary hormones were discussed in the last part of the essay. Together, the CNS and pituitary effects of hypothalamic peptides and MSH provide intriguing examples of areas of investigation which can be expected to be greatly expanded in the future."}
{"id": "PMID:30630", "title": "Slow association-dissociation equilibrium of NADP-linked isocitrate dehydrogenase from beef liver in relation to catalytic activity.", "content": "In this paper experiments are reported which show evidence for a relation between quaternary structure and catalytic activity of cytoplasmic NADP-linked isocitrate dehydrogenase from beef liver. The inactivation of the enzyme occurring upon dilution and the plots of the catalytic activity versus the enzyme concentration indicate that the monomeric species is catalytically inactive and that the monomer-dimer equilibrium is shifted towards the dimer upon binding of the substrate magnesium isocitrate complex. The association of the enzyme following binding of the substrate takes place at a rate comparable with that of the enzymatic reaction, which results in a 'hysteretic' behaviour of the enzyme. The possibility is discussed that slow changes in quaternary structure can give rise to a physiological regulation of the enzymatic activity.", "contents": "Slow association-dissociation equilibrium of NADP-linked isocitrate dehydrogenase from beef liver in relation to catalytic activity. In this paper experiments are reported which show evidence for a relation between quaternary structure and catalytic activity of cytoplasmic NADP-linked isocitrate dehydrogenase from beef liver. The inactivation of the enzyme occurring upon dilution and the plots of the catalytic activity versus the enzyme concentration indicate that the monomeric species is catalytically inactive and that the monomer-dimer equilibrium is shifted towards the dimer upon binding of the substrate magnesium isocitrate complex. The association of the enzyme following binding of the substrate takes place at a rate comparable with that of the enzymatic reaction, which results in a 'hysteretic' behaviour of the enzyme. The possibility is discussed that slow changes in quaternary structure can give rise to a physiological regulation of the enzymatic activity."}
{"id": "PMID:30631", "title": "Nuclear-magnetic-resonance study of aggregations and conformations of melanostatin and related peptides.", "content": "The 1H and 13C nuclear magnetic resonance spectra of melanostatin (Pro-Leu-Gly-NH2) and related peptides (Pro-Leu-Gly, Z-Pro-Leu-Gly, Z-Pro-Leu-Gly-NH2 and Z-Pro-Leu-Gly-OCH3, where Z = benzyloxycarbonyl) were analysed in a variety of solvents. At physiological pH, the melanostatin molecule is N-protonated in aqueous solution. The concentration dependences of the chemical shifts of amide-proton and carbonyl-carbon resonances and of proton spin-lattice relaxation times were observed in relation to molecular aggregations. In dimethylsulfoxide solution, aggregations were observed for N-protonated melanostatin and Pro-Leu-Gly prepared with HCl and for the Na salt of Z-Pro-Leu-Gly but not for N-protonated melanostatin prepared with HClO4 or HNO3, unprotonated melanostatin, Z-Pro-Leu-Gly-NH2, or Z-Pro-Leu-Gly-OCH3. The leucine NH and glycine CO groups of N-protonated melanostatin are involved in the intermolecular hydrogen bonds of aggregates. The leucine NH group of N-protonated Pro-Leu-Gly also forms the intermolecular hydrogen bond. The solvent and temperature dependences of the chemical shifts of amide-proton and carbonyl-carbon resonances were measured to determine intramolecular hydrogen bonding. In dimethylsulfoxide solution, N-protonated melanostatin molecules in part take the beta-turn structure and the trans carboxamide NH proton and carbonyl oxygen of the proline residue form an intramolecular hydrogen bond.", "contents": "Nuclear-magnetic-resonance study of aggregations and conformations of melanostatin and related peptides. The 1H and 13C nuclear magnetic resonance spectra of melanostatin (Pro-Leu-Gly-NH2) and related peptides (Pro-Leu-Gly, Z-Pro-Leu-Gly, Z-Pro-Leu-Gly-NH2 and Z-Pro-Leu-Gly-OCH3, where Z = benzyloxycarbonyl) were analysed in a variety of solvents. At physiological pH, the melanostatin molecule is N-protonated in aqueous solution. The concentration dependences of the chemical shifts of amide-proton and carbonyl-carbon resonances and of proton spin-lattice relaxation times were observed in relation to molecular aggregations. In dimethylsulfoxide solution, aggregations were observed for N-protonated melanostatin and Pro-Leu-Gly prepared with HCl and for the Na salt of Z-Pro-Leu-Gly but not for N-protonated melanostatin prepared with HClO4 or HNO3, unprotonated melanostatin, Z-Pro-Leu-Gly-NH2, or Z-Pro-Leu-Gly-OCH3. The leucine NH and glycine CO groups of N-protonated melanostatin are involved in the intermolecular hydrogen bonds of aggregates. The leucine NH group of N-protonated Pro-Leu-Gly also forms the intermolecular hydrogen bond. The solvent and temperature dependences of the chemical shifts of amide-proton and carbonyl-carbon resonances were measured to determine intramolecular hydrogen bonding. In dimethylsulfoxide solution, N-protonated melanostatin molecules in part take the beta-turn structure and the trans carboxamide NH proton and carbonyl oxygen of the proline residue form an intramolecular hydrogen bond."}
{"id": "PMID:30632", "title": "Histidine in the nucleotide-binding site of NADP-linked isocitrate dehydrogenase from pig heart.", "content": "Incubation of pig heart NADP-dependent isocitrate dehydrogenase with ethoxyformic anhydride (diethylpyrocarbonate) at pH 6.2 results in a 9-fold greater rate of loss of dehydrogenase than of oxalosuccinate decarboxylase activity. The rate constants for loss of dehydrogenase and decarboxylase activities depend on the basic form of ionizable groups with pK values of 5.67 and 7.05, respectively, suggesting that inactivation of the two catalytic functions results from reaction with different amino acid residues. The rate of loss of dehydrogenase activity is decreased only slightly in the presence of manganous isocitrate, but is reduced up to 10-fold by addition of the coenzymes or coenzyme analogues, such as 2'-phosphoadenosine 5'-diphosphoribose (Rib-P2-Ado-P). Enzyme modified at pH 5.8 fails to bind NADPH, but exhibits manganese-enhanced isocitrate binding typical of native enzyme, indicating that reaction takes place in the region of the nucleotide binding site. Dissociation constants for enzyme . coenzyme-analogue complexes have been calculated from the decrease in the rate of inactivation as a function of analogue concentration. In the presence of isocitrate, activating metals (Mn2+, Mg2+, Zn2+) decrease the Kd value for enzyme . Rib-P2-Ado-P, while the inhibitor Ca2+ increases Kd. The strengthened binding of nucleotide produced by activating metal-isocitrate complexes may be essential for the catalytic reaction, reflecting an optimal orientation of NADP+ to facilitate hydride transfer. Measurements of ethoxyformyl-histidine formation at 240 nm and of incorporation of [14C]ethoxy groups in the presence and absence of Rib-P2-Ado-P indicate that loss of activity may be related to modification of approximately one histidine. The critical histidine appears to be located in the nucleotide binding site in a region distal from the substrate binding site.", "contents": "Histidine in the nucleotide-binding site of NADP-linked isocitrate dehydrogenase from pig heart. Incubation of pig heart NADP-dependent isocitrate dehydrogenase with ethoxyformic anhydride (diethylpyrocarbonate) at pH 6.2 results in a 9-fold greater rate of loss of dehydrogenase than of oxalosuccinate decarboxylase activity. The rate constants for loss of dehydrogenase and decarboxylase activities depend on the basic form of ionizable groups with pK values of 5.67 and 7.05, respectively, suggesting that inactivation of the two catalytic functions results from reaction with different amino acid residues. The rate of loss of dehydrogenase activity is decreased only slightly in the presence of manganous isocitrate, but is reduced up to 10-fold by addition of the coenzymes or coenzyme analogues, such as 2'-phosphoadenosine 5'-diphosphoribose (Rib-P2-Ado-P). Enzyme modified at pH 5.8 fails to bind NADPH, but exhibits manganese-enhanced isocitrate binding typical of native enzyme, indicating that reaction takes place in the region of the nucleotide binding site. Dissociation constants for enzyme . coenzyme-analogue complexes have been calculated from the decrease in the rate of inactivation as a function of analogue concentration. In the presence of isocitrate, activating metals (Mn2+, Mg2+, Zn2+) decrease the Kd value for enzyme . Rib-P2-Ado-P, while the inhibitor Ca2+ increases Kd. The strengthened binding of nucleotide produced by activating metal-isocitrate complexes may be essential for the catalytic reaction, reflecting an optimal orientation of NADP+ to facilitate hydride transfer. Measurements of ethoxyformyl-histidine formation at 240 nm and of incorporation of [14C]ethoxy groups in the presence and absence of Rib-P2-Ado-P indicate that loss of activity may be related to modification of approximately one histidine. The critical histidine appears to be located in the nucleotide binding site in a region distal from the substrate binding site."}
{"id": "PMID:30633", "title": "Plasma hypoxanthine levels in pigs during acute hypoxemia. A correlation between lactate and base deficit concentrations.", "content": "Tissue hypoxia was induced in pigs by artificial ventilation with 6% O2 in N2 for 18 min. Base deficit, lactate and hypoxanthine increased linearily during this period, and were significantly higher than initial values in the course of 6 min of hypoxemia. High correlation coefficients between hypoxanthine and lactate (mean 0.98) and between hypoxanthine and base deficit (mean 0.98) were found. During the recovery period when the animals were ventilated with air, high correlation coefficients between lactate and hypoxanthine (mean 0.75) and between base deficit and hypoxanthine (mean 0.83) were also found. It is concluded that plasma hypoxanthine concentrations should be used to assess tissue hypoxia also in clinical situations.", "contents": "Plasma hypoxanthine levels in pigs during acute hypoxemia. A correlation between lactate and base deficit concentrations. Tissue hypoxia was induced in pigs by artificial ventilation with 6% O2 in N2 for 18 min. Base deficit, lactate and hypoxanthine increased linearily during this period, and were significantly higher than initial values in the course of 6 min of hypoxemia. High correlation coefficients between hypoxanthine and lactate (mean 0.98) and between hypoxanthine and base deficit (mean 0.98) were found. During the recovery period when the animals were ventilated with air, high correlation coefficients between lactate and hypoxanthine (mean 0.75) and between base deficit and hypoxanthine (mean 0.83) were also found. It is concluded that plasma hypoxanthine concentrations should be used to assess tissue hypoxia also in clinical situations."}
{"id": "PMID:30635", "title": "Stimulation of immune reactivity by methoxy-substituted glycerol ethers incorporated into the feed.", "content": "In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes.", "contents": "Stimulation of immune reactivity by methoxy-substituted glycerol ethers incorporated into the feed. In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes."}
{"id": "PMID:30636", "title": "Effect of chronic clonidine treatment and withdrawal on tyrosine hydroxylase activity in peripheral ganglia and the locus coeruleus.", "content": "As is observed clinically, cessation of chronic clonidine treatment in the rat results in a syndrome characterized by sympathetic hyperactivity. After three weeks of chronic oral administration of clonidine, tyrosine hydroxylase (TOH) activity was unchanged in superior cervical ganglia and locus coeruleus, but was reduced (45%) in the celiac ganglia. Abrupt cessation of treatment resulted in increases in TOH activity in superior cervical and celiac ganglia (to 135 and 250% of controls) and in the locus coeruleus (170% of control). These data suggest a selective effect of clonidine treatment and withdrawal on vasomotor fibers. A mechanism explaining physical dependence on clonidine is proposed.", "contents": "Effect of chronic clonidine treatment and withdrawal on tyrosine hydroxylase activity in peripheral ganglia and the locus coeruleus. As is observed clinically, cessation of chronic clonidine treatment in the rat results in a syndrome characterized by sympathetic hyperactivity. After three weeks of chronic oral administration of clonidine, tyrosine hydroxylase (TOH) activity was unchanged in superior cervical ganglia and locus coeruleus, but was reduced (45%) in the celiac ganglia. Abrupt cessation of treatment resulted in increases in TOH activity in superior cervical and celiac ganglia (to 135 and 250% of controls) and in the locus coeruleus (170% of control). These data suggest a selective effect of clonidine treatment and withdrawal on vasomotor fibers. A mechanism explaining physical dependence on clonidine is proposed."}
{"id": "PMID:30638", "title": "Effects of alpha-agonists on circulatory responses to somatic afferent nerve stimulation.", "content": "The effect of intracisternal (i.c.m.) injection of clonidine, noradrenaline, and piperoxane on the pressor response to electrical stimulation of a peripheral somatic afferent nerve was investigated using anaesthetized cats. It was found that noradrenaline caused a depression of the magnitude of the pressor response and this effect was antagonized by subsequent injection of piperoxane i.c.m. In contrast, clonidine had no significant effect on the magnitude of the somatic pressor reflex but caused a dose-dependent prolongation of the reflex after cessation of nerve stimulation. This prolongation was antagonized by piperoxane which also caused an increase in the magnitude of the reflex. Piperoxane alone had no significant effect on the magnitude or duration of the reflex. Neither magnitude nor duration of the somatic pressor reflex was influenced significantly by a reduction in resting blood pressure. It is suggested that clonidine and noradrenaline act at different sites within the central nervous system to produce qualitatively different changes in the efferent sympathetic discharge pattern modulating the somatic pressor reflex.", "contents": "Effects of alpha-agonists on circulatory responses to somatic afferent nerve stimulation. The effect of intracisternal (i.c.m.) injection of clonidine, noradrenaline, and piperoxane on the pressor response to electrical stimulation of a peripheral somatic afferent nerve was investigated using anaesthetized cats. It was found that noradrenaline caused a depression of the magnitude of the pressor response and this effect was antagonized by subsequent injection of piperoxane i.c.m. In contrast, clonidine had no significant effect on the magnitude of the somatic pressor reflex but caused a dose-dependent prolongation of the reflex after cessation of nerve stimulation. This prolongation was antagonized by piperoxane which also caused an increase in the magnitude of the reflex. Piperoxane alone had no significant effect on the magnitude or duration of the reflex. Neither magnitude nor duration of the somatic pressor reflex was influenced significantly by a reduction in resting blood pressure. It is suggested that clonidine and noradrenaline act at different sites within the central nervous system to produce qualitatively different changes in the efferent sympathetic discharge pattern modulating the somatic pressor reflex."}
{"id": "PMID:30639", "title": "Behavioural evidence for GABAergic activity of the benzodiazepine flurazepam.", "content": "Following reports that unilateral intranigral injections of putative GABAergic drugs induce contralateral rotational behaviour in rats, the effects of similar injections of the benzodiazepine flurazepam have been studied. Flurazepam mimicked the effects of the GABA agonist muscimol and the GABA analogue baclofen by inducing a dose-related contralateral rotation. This response was anatomically associated with the GABA-rich zona reticulata of the substantia nigra and was attenuated by the GABA antagonist picrotoxin but not by the dopamine antagonist haloperidol or by destruction of the ipsilateral nigrostriatal dopamine pathway with 6-hydroxydopamine. These results suggest that in this behavioural model flurazepam may show GABAergic activity by indirectly enhancing GABA transmission at synapses with receptors located on nigral non-dopaminergic neurons controlling postural asymmetry.", "contents": "Behavioural evidence for GABAergic activity of the benzodiazepine flurazepam. Following reports that unilateral intranigral injections of putative GABAergic drugs induce contralateral rotational behaviour in rats, the effects of similar injections of the benzodiazepine flurazepam have been studied. Flurazepam mimicked the effects of the GABA agonist muscimol and the GABA analogue baclofen by inducing a dose-related contralateral rotation. This response was anatomically associated with the GABA-rich zona reticulata of the substantia nigra and was attenuated by the GABA antagonist picrotoxin but not by the dopamine antagonist haloperidol or by destruction of the ipsilateral nigrostriatal dopamine pathway with 6-hydroxydopamine. These results suggest that in this behavioural model flurazepam may show GABAergic activity by indirectly enhancing GABA transmission at synapses with receptors located on nigral non-dopaminergic neurons controlling postural asymmetry."}
{"id": "PMID:30640", "title": "The effects of HGCl2 and mersalyl on mechanisms regulating intracellular calcium and transmitter release.", "content": "HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lower concentrations of HgCl2 showed a stimulatory effect on mitochondrial calcium uptake. It is suggested that the effect of mercurials on transmitter release is mediated via changes of the intracellular calcium ion concentration.", "contents": "The effects of HGCl2 and mersalyl on mechanisms regulating intracellular calcium and transmitter release. HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lower concentrations of HgCl2 showed a stimulatory effect on mitochondrial calcium uptake. It is suggested that the effect of mercurials on transmitter release is mediated via changes of the intracellular calcium ion concentration."}
{"id": "PMID:30650", "title": "Angiotensin, thirst, and sodium appetite: retrospect and prospect.", "content": "The fact that drinking in response to some hypovolemic stimuli was attenuated by nephrectomy but not by ureteric ligation led to the suggestion that the renal renin-angiotensin system may play a role in hypovolemic thirst. The isolation of a thirst factor from the kidney and the demonstration that this substance was renin supported the hypothesis. Subsequently, it was shown that the effects of renin on drinking were mediated through angiotensin II, which proved to be a potent dipsogenic substance when administered systemically or injected directly into the brain. Recently, it has been shown that angiotensin II, infused intravenously or through the carotid artery at rates that produce increases in plasma angiotensin II levels similar to those that occur in mild sodium depletion, causes the water-replete animal to drink. This discovery establishes that angiotensin is a physiological stimulus to drinking but it leaves open the question of the extent of the involvement of renal renin in normal thirst. Other unsolved problems are the role of cerebral isorenin in angiotensin thirst and its relationship with renal renin, and in view of its stimulating action on sodium intake when infused into the brain, whether angiotensin plays a significant role in sodium appetite.", "contents": "Angiotensin, thirst, and sodium appetite: retrospect and prospect. The fact that drinking in response to some hypovolemic stimuli was attenuated by nephrectomy but not by ureteric ligation led to the suggestion that the renal renin-angiotensin system may play a role in hypovolemic thirst. The isolation of a thirst factor from the kidney and the demonstration that this substance was renin supported the hypothesis. Subsequently, it was shown that the effects of renin on drinking were mediated through angiotensin II, which proved to be a potent dipsogenic substance when administered systemically or injected directly into the brain. Recently, it has been shown that angiotensin II, infused intravenously or through the carotid artery at rates that produce increases in plasma angiotensin II levels similar to those that occur in mild sodium depletion, causes the water-replete animal to drink. This discovery establishes that angiotensin is a physiological stimulus to drinking but it leaves open the question of the extent of the involvement of renal renin in normal thirst. Other unsolved problems are the role of cerebral isorenin in angiotensin thirst and its relationship with renal renin, and in view of its stimulating action on sodium intake when infused into the brain, whether angiotensin plays a significant role in sodium appetite."}
{"id": "PMID:30653", "title": "The effect of temperature on sperm motility. II. Is bacterial growth a factor?", "content": "The previous demonstration that sperm kept at body temperature (37 degrees C) had a marked deterioration in motility accompanied by an overgrowth of bacteria in the semen and a concomitant decrease in pH led to this study to test the hypothesis that the decrease in motility was caused by the bacteria or by bacterial alteration of seminal pH. Semen specimens from fertile prevasectomy patients with and without added antibiotics were maintained at 20 degrees C and 37 degrees C and evaluated at 3, 12, and 18 hours after collection. There was still a significant deterioration in spermatozoal motility in the samples kept at 37 degrees C even when bacterial growth and change in pH were prevented by buffered antibiotics. Although the decrease in spermatozoal motility at body temperature may in part be attributed to bacterial growth or the products of bacterial metabolism, clearly another factor is present related to time and temperature and independent of the presence of bacteria.", "contents": "The effect of temperature on sperm motility. II. Is bacterial growth a factor? The previous demonstration that sperm kept at body temperature (37 degrees C) had a marked deterioration in motility accompanied by an overgrowth of bacteria in the semen and a concomitant decrease in pH led to this study to test the hypothesis that the decrease in motility was caused by the bacteria or by bacterial alteration of seminal pH. Semen specimens from fertile prevasectomy patients with and without added antibiotics were maintained at 20 degrees C and 37 degrees C and evaluated at 3, 12, and 18 hours after collection. There was still a significant deterioration in spermatozoal motility in the samples kept at 37 degrees C even when bacterial growth and change in pH were prevented by buffered antibiotics. Although the decrease in spermatozoal motility at body temperature may in part be attributed to bacterial growth or the products of bacterial metabolism, clearly another factor is present related to time and temperature and independent of the presence of bacteria."}
{"id": "PMID:30654", "title": "[Endocrine apparatus of human gastric mucosa].", "content": "Endocrine cells of the gastric fundal and pyloric mucosa in patients suffering from gastric and duodenal ulcers with different gastric juice acidity, were studied. At hyperacid ulcers, the number of argyrhilic endocrine cells of gastric fundus was increased to 218 +/- 21.1 as compared with the normal acidity 164 +/- 14.8, while it was decreased to 97 +/- 15.1 as compared with hypoacidity. Argentaffinic cells were found in patients with hypo- and unacid gastric juice only. The electron microscopy revealed six types of endocrine cells (A-like, ECL, G, D, D1, EC). The ultrastructural changes of A-like, ECL, and G cells in patients with hyperacid gastric juice indicated their high functional activity. A balance seems to exist between activating and inhibiting systems of the endocrine apparatus of gastric mucosa which accounts for the hyperacidity of the gastric juice.", "contents": "[Endocrine apparatus of human gastric mucosa]. Endocrine cells of the gastric fundal and pyloric mucosa in patients suffering from gastric and duodenal ulcers with different gastric juice acidity, were studied. At hyperacid ulcers, the number of argyrhilic endocrine cells of gastric fundus was increased to 218 +/- 21.1 as compared with the normal acidity 164 +/- 14.8, while it was decreased to 97 +/- 15.1 as compared with hypoacidity. Argentaffinic cells were found in patients with hypo- and unacid gastric juice only. The electron microscopy revealed six types of endocrine cells (A-like, ECL, G, D, D1, EC). The ultrastructural changes of A-like, ECL, and G cells in patients with hyperacid gastric juice indicated their high functional activity. A balance seems to exist between activating and inhibiting systems of the endocrine apparatus of gastric mucosa which accounts for the hyperacidity of the gastric juice."}
{"id": "PMID:30655", "title": "[Gastric secretion in rats during long-term histamine administration].", "content": "The acid--forming, acid--neutralizing functions of the stomach, morphological state of its walls and level of histamine in the blood were studied in control rats and in rats subjected to continuous histamine administration. In the latter, intensive elevation of intragastric acidity in empty stomach, an increase in the histamine contents in the blood, and distrophic processes in the wall of stomach occurred. The functional--morphological data obtained suggest remarkable adaptational abilities of the stomach.", "contents": "[Gastric secretion in rats during long-term histamine administration]. The acid--forming, acid--neutralizing functions of the stomach, morphological state of its walls and level of histamine in the blood were studied in control rats and in rats subjected to continuous histamine administration. In the latter, intensive elevation of intragastric acidity in empty stomach, an increase in the histamine contents in the blood, and distrophic processes in the wall of stomach occurred. The functional--morphological data obtained suggest remarkable adaptational abilities of the stomach."}
{"id": "PMID:30666", "title": "Hemolytic anemia in patients receiving sulfasalazine.", "content": "Hemolytic anemia is a well-recognized complication of sulfasalazine treatment. 17 of 40 (43%) patients with inflammatory bowel disease receiving sulfasalazine had evidence of hemolysis as detected by starch gel electrophoresis. Only 47% (8) of patients with hemolysis had Heinz body formation. The hemoglobin was significantly reduced in patients with hemolysis and 53% had a reticulocyte count of greater than 5%. A significant correlation was noted between hemolysis and serum sulfapyridine level, but no correlation was seen with serum sulfasalazine level. There was no significant difference in disease extent or activity in patients with hemolysis compared to those without hemolysis. Hemolysis is not a rare side-effect of sulfasalazine therapy. Heinz body formation is not invariably found in sulfasalazine-induced hemolysis.", "contents": "Hemolytic anemia in patients receiving sulfasalazine. Hemolytic anemia is a well-recognized complication of sulfasalazine treatment. 17 of 40 (43%) patients with inflammatory bowel disease receiving sulfasalazine had evidence of hemolysis as detected by starch gel electrophoresis. Only 47% (8) of patients with hemolysis had Heinz body formation. The hemoglobin was significantly reduced in patients with hemolysis and 53% had a reticulocyte count of greater than 5%. A significant correlation was noted between hemolysis and serum sulfapyridine level, but no correlation was seen with serum sulfasalazine level. There was no significant difference in disease extent or activity in patients with hemolysis compared to those without hemolysis. Hemolysis is not a rare side-effect of sulfasalazine therapy. Heinz body formation is not invariably found in sulfasalazine-induced hemolysis."}
{"id": "PMID:30668", "title": "In vitro binding of 2-acetaminofluorene to RNA and protein with rat liver microsomes.", "content": "Covalent binding of 2-acetaminofluorene[9-14C] with exogenous Torula yeast RNA and endogenous protein was investigated in liver microsome system in vitro. The binding to protein was 100 times higher than that to RNA. Requirement of NADPH, effectiveness of methylcholanthrene treatment, and inhibition by 7,8-benzoflavone suggest possible involvement of mixed-function oxidases in this binding. The binding was not due to contaminated cytosol in the microsome fraction. Addition of cytosol, sulfate ion, and ATP diminished the binding. Parallel experiments using N-hydroxy-2-acetaminofluorene[9-14C] denied major contribution of this metabolite to the binding of 2-acetaminofluorene in the microsome system. Ring-hydroxylated product was suggested as a possible metabolite for the binding.", "contents": "In vitro binding of 2-acetaminofluorene to RNA and protein with rat liver microsomes. Covalent binding of 2-acetaminofluorene[9-14C] with exogenous Torula yeast RNA and endogenous protein was investigated in liver microsome system in vitro. The binding to protein was 100 times higher than that to RNA. Requirement of NADPH, effectiveness of methylcholanthrene treatment, and inhibition by 7,8-benzoflavone suggest possible involvement of mixed-function oxidases in this binding. The binding was not due to contaminated cytosol in the microsome fraction. Addition of cytosol, sulfate ion, and ATP diminished the binding. Parallel experiments using N-hydroxy-2-acetaminofluorene[9-14C] denied major contribution of this metabolite to the binding of 2-acetaminofluorene in the microsome system. Ring-hydroxylated product was suggested as a possible metabolite for the binding."}
{"id": "PMID:30669", "title": "Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine.", "content": "Prostaglandin E2 (PGE2) level in rectal mucosa excised from 17 patients suffering from ulcerative colitis was 2-fold higher than that found in rectal mucosa of 17 normal subjects: 2.0 +/- 0.4 and 0.9 +/- 0.2 ng per mg of wet tissue, respectively. Accumulation of PGE 2 in 24-hr cultures of rectal mucosa specimens obtained from patients with ulcerative colitis was 112% higher than that observed in cultures from control subjects. Addition of sulfasalazine, sulfapyridine, and 5-aminosalicylic, acid to the culture medium of ulcerative colitis mucosa resulted in inhibition of PGE2 production by 34, 32, and 62%, respectively, compared to rectal specimens cultured in drug-free medium. These results suggest that PGE may mediate the inflammatory response in ulcerative colitis and that some of the therapeutic effect of sulfasalazine and its constituents are related to the inhibition of PGE synthesis.", "contents": "Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Prostaglandin E2 (PGE2) level in rectal mucosa excised from 17 patients suffering from ulcerative colitis was 2-fold higher than that found in rectal mucosa of 17 normal subjects: 2.0 +/- 0.4 and 0.9 +/- 0.2 ng per mg of wet tissue, respectively. Accumulation of PGE 2 in 24-hr cultures of rectal mucosa specimens obtained from patients with ulcerative colitis was 112% higher than that observed in cultures from control subjects. Addition of sulfasalazine, sulfapyridine, and 5-aminosalicylic, acid to the culture medium of ulcerative colitis mucosa resulted in inhibition of PGE2 production by 34, 32, and 62%, respectively, compared to rectal specimens cultured in drug-free medium. These results suggest that PGE may mediate the inflammatory response in ulcerative colitis and that some of the therapeutic effect of sulfasalazine and its constituents are related to the inhibition of PGE synthesis."}
{"id": "PMID:30670", "title": "Effect of the acid secretory state on intramural pH of rabbit gastric mucosa.", "content": "Intramural pH  of the gastric mucosa was measured using a microelectrode technique in rabbit gastric pouches under different secretory conditions and luminal acidity. Exposure of spontaneously secreting or metiamide-treated fundic pouches to a relatively high concentration of luminal acid. HCl 120 mM, for 60 min, led to a marked net loss of luminal H+ which was associated with a significant decrease in the intramural pH (7.28 +/- 0.09 to 6.88 +/- 0.10 and 7.23 +/- 0.07 to 6.99 +/- 0.09, respectively). A linear relationship was observed between the rates of net disappearance of luminal acid and the intramural pH. All 10 spontaneously secreting and five metiamide-treated pouches had superficial mucosal erosions. In contrast, when fundic pouches were exposed to luminal acid in histamine-treated animals, the net loss of luminal H+ was negligible and the intramural pH remained at its base-line level (7.25 +/- 0.07). Histamine stimulation without acid in the lumen caused a small but insignificant increase in the intramural pH (7.27 +/- 0.03 to 7.39 +/- 0.05). Only three of the eight histamine-treated fundic pouches had lesions. In the antral pouches the intramural pH changes in response to exposure to luminal acid were smaller and histamine treatment did not influence the intramural pH. None of the antral pouches had lesions. The results suggest that acidification of the tissue by the diffusion of luminal acid may be an important factor in the pathogenesis of acute gastric ulceration. The acid secretory state of the gastric mucosa can significantly influence the acid-base balance in the mucosa and thus modify its response to acid diffusing from the lumen. Histamine stimulation protected the gastric mucosa by improving its buffering capacity and/or otherwise decreasing the diffusion of H+ from the lumen into the mucosa.", "contents": "Effect of the acid secretory state on intramural pH of rabbit gastric mucosa. Intramural pH  of the gastric mucosa was measured using a microelectrode technique in rabbit gastric pouches under different secretory conditions and luminal acidity. Exposure of spontaneously secreting or metiamide-treated fundic pouches to a relatively high concentration of luminal acid. HCl 120 mM, for 60 min, led to a marked net loss of luminal H+ which was associated with a significant decrease in the intramural pH (7.28 +/- 0.09 to 6.88 +/- 0.10 and 7.23 +/- 0.07 to 6.99 +/- 0.09, respectively). A linear relationship was observed between the rates of net disappearance of luminal acid and the intramural pH. All 10 spontaneously secreting and five metiamide-treated pouches had superficial mucosal erosions. In contrast, when fundic pouches were exposed to luminal acid in histamine-treated animals, the net loss of luminal H+ was negligible and the intramural pH remained at its base-line level (7.25 +/- 0.07). Histamine stimulation without acid in the lumen caused a small but insignificant increase in the intramural pH (7.27 +/- 0.03 to 7.39 +/- 0.05). Only three of the eight histamine-treated fundic pouches had lesions. In the antral pouches the intramural pH changes in response to exposure to luminal acid were smaller and histamine treatment did not influence the intramural pH. None of the antral pouches had lesions. The results suggest that acidification of the tissue by the diffusion of luminal acid may be an important factor in the pathogenesis of acute gastric ulceration. The acid secretory state of the gastric mucosa can significantly influence the acid-base balance in the mucosa and thus modify its response to acid diffusing from the lumen. Histamine stimulation protected the gastric mucosa by improving its buffering capacity and/or otherwise decreasing the diffusion of H+ from the lumen into the mucosa."}
{"id": "PMID:30676", "title": "Uneven and transient secretin release after a liquid test meal.", "content": "In order to test the hypothesis that secretin may be released intermittently after feeding, the plasma secretin concentration was measured at short intervals, and the duodenal pH continuously recorded, after a liquid test meal in 10 human subjects. Secretin was measured with a radioimmunoassay in which the entire molecule is specifically recognized and the immunoreactivities of human secretin and of the porcine peptide used as standard are similar. In the total group, no significant variation of the mean plasma secretin concentration above basal was observed within 45 min after feeding. Analysis of the individual patterns revealed that secretin was released transiently in 5 of the 10 subjects, namely those showing variations of the duodenal pH down to or below 4.0 at some time after the meal. The mean peak delta secretin in these subjects was 7.2 pg ml-1 of plasma. In 7 additional subjects, bolus intravenous injections of 0.005 and 0.01 clinical units kg-1 of porcine secretin resulted in peak delta secretin concentrations of 5.5 and 10.5 pg ml-1, respectively, and were followed by a significant increase of bicarbonate output in the duodenal aspirate. These results indicate that secretin is released unevenly and intermittently in the early period after a liquid meal in man, in amounts that seem sufficient for the initiation of a significant bicarbonate response.", "contents": "Uneven and transient secretin release after a liquid test meal. In order to test the hypothesis that secretin may be released intermittently after feeding, the plasma secretin concentration was measured at short intervals, and the duodenal pH continuously recorded, after a liquid test meal in 10 human subjects. Secretin was measured with a radioimmunoassay in which the entire molecule is specifically recognized and the immunoreactivities of human secretin and of the porcine peptide used as standard are similar. In the total group, no significant variation of the mean plasma secretin concentration above basal was observed within 45 min after feeding. Analysis of the individual patterns revealed that secretin was released transiently in 5 of the 10 subjects, namely those showing variations of the duodenal pH down to or below 4.0 at some time after the meal. The mean peak delta secretin in these subjects was 7.2 pg ml-1 of plasma. In 7 additional subjects, bolus intravenous injections of 0.005 and 0.01 clinical units kg-1 of porcine secretin resulted in peak delta secretin concentrations of 5.5 and 10.5 pg ml-1, respectively, and were followed by a significant increase of bicarbonate output in the duodenal aspirate. These results indicate that secretin is released unevenly and intermittently in the early period after a liquid meal in man, in amounts that seem sufficient for the initiation of a significant bicarbonate response."}
{"id": "PMID:30679", "title": "Gastroesophageal reflux and bleeding esophageal varices.", "content": "The incidence of gastroesophageal reflux was evaluated with the use of a pH probe in 12 patients with cirrhosis and recent variceal hemorrhage and in 15 healthy control subjects. Short episodes of reflux occurred in 42% of the patients and in 47% of the controls. During an observation period of 1 hr, the cumulative duration of reflux was similar in patients (2.5 +/- 1.3 min) and controls (3.1 +/- 1.4 min). Mean lower esophageal sphincter pressures were normal in both groups but did not show a significant correlation with the duration of reflux. These data support previous observations that gastroesophageal reflux dose not appear to be a contributing factor in the development of variceal hemorrhage.", "contents": "Gastroesophageal reflux and bleeding esophageal varices. The incidence of gastroesophageal reflux was evaluated with the use of a pH probe in 12 patients with cirrhosis and recent variceal hemorrhage and in 15 healthy control subjects. Short episodes of reflux occurred in 42% of the patients and in 47% of the controls. During an observation period of 1 hr, the cumulative duration of reflux was similar in patients (2.5 +/- 1.3 min) and controls (3.1 +/- 1.4 min). Mean lower esophageal sphincter pressures were normal in both groups but did not show a significant correlation with the duration of reflux. These data support previous observations that gastroesophageal reflux dose not appear to be a contributing factor in the development of variceal hemorrhage."}
{"id": "PMID:30680", "title": "Topical effects of 16,16 dimethyl prostaglandin E2 on gastric acid secretion and mucosal permeability to hydrogen ions in dogs.", "content": "The effects of luminal instillation of 16,16 dimethyl PGE2 (dmPGE2) on gastric acid secretion and back diffusion of H+ were studied in anaesthetised dogs which were prepared with a segment of the greater curvature of the stomach mounted in a double lumen chamber. This model permitted simultaneous evaluation of two segments of mucosa, one control and the other test, supplied by the same vascular pedicle. Imfusion of histamine (1.0 microgram/kg/min, intravenously) stimulated brisk acid secretion in both chambers. Topical application of 25 microgram dmPGE2 in 20 ml 0.3 M HC1 to the test chamber for 30 minutes prevented acid secretion from the test mucosa during a second histamine infusion. Since the control chamber showed no evidence of inhibition this indicates that dmPGE2 acted directly on the secretory cells, rather than after absorption from the bloodstream. This observation, however, does not exclude a possible local effect on mucosal blood flow. Direct exposure of the gastric mucosa to dmPGE2 increased the rate of back diffusion of H+ because of disruption of the permeability barrier, indicated by increased H+ back diffusion, Na+ efflux, and a reduction in potential difference. However, H+ loss was small compared to the reduction in acid output.", "contents": "Topical effects of 16,16 dimethyl prostaglandin E2 on gastric acid secretion and mucosal permeability to hydrogen ions in dogs. The effects of luminal instillation of 16,16 dimethyl PGE2 (dmPGE2) on gastric acid secretion and back diffusion of H+ were studied in anaesthetised dogs which were prepared with a segment of the greater curvature of the stomach mounted in a double lumen chamber. This model permitted simultaneous evaluation of two segments of mucosa, one control and the other test, supplied by the same vascular pedicle. Imfusion of histamine (1.0 microgram/kg/min, intravenously) stimulated brisk acid secretion in both chambers. Topical application of 25 microgram dmPGE2 in 20 ml 0.3 M HC1 to the test chamber for 30 minutes prevented acid secretion from the test mucosa during a second histamine infusion. Since the control chamber showed no evidence of inhibition this indicates that dmPGE2 acted directly on the secretory cells, rather than after absorption from the bloodstream. This observation, however, does not exclude a possible local effect on mucosal blood flow. Direct exposure of the gastric mucosa to dmPGE2 increased the rate of back diffusion of H+ because of disruption of the permeability barrier, indicated by increased H+ back diffusion, Na+ efflux, and a reduction in potential difference. However, H+ loss was small compared to the reduction in acid output."}
{"id": "PMID:30681", "title": "Gastric secretion and basal gastrin concentration in bilharzial hepatic fibrosis.", "content": "Gastric secretion and fasting plasma gastrin levels were investigated in 26 patients with bilharzial hepatic fibrosis and 26 controls. The groups did not differ in their basal secretion. When stimulated by intravenous infusion of histamine the maximal acid output in patients with bilharzial hepatic fibrosis was significantly less than in the control group. This was unlikely to be a result of neutralisation by reflux of alkaline duodenal contents as the volumes of reflux were not different from control subjects, but was compatible with a true reduction in gastric secretion as assessed by two-component hypothesis. Neither the lowered gastric acidity nor the liver damage in patients with bilharzial hepatic fibrosis correlated with circulating gastrin. The fasting levels of plasma gastrin in these patients were not different from controls. As in other liver diseases the cause of diminished gastric secretion remains unclear.", "contents": "Gastric secretion and basal gastrin concentration in bilharzial hepatic fibrosis. Gastric secretion and fasting plasma gastrin levels were investigated in 26 patients with bilharzial hepatic fibrosis and 26 controls. The groups did not differ in their basal secretion. When stimulated by intravenous infusion of histamine the maximal acid output in patients with bilharzial hepatic fibrosis was significantly less than in the control group. This was unlikely to be a result of neutralisation by reflux of alkaline duodenal contents as the volumes of reflux were not different from control subjects, but was compatible with a true reduction in gastric secretion as assessed by two-component hypothesis. Neither the lowered gastric acidity nor the liver damage in patients with bilharzial hepatic fibrosis correlated with circulating gastrin. The fasting levels of plasma gastrin in these patients were not different from controls. As in other liver diseases the cause of diminished gastric secretion remains unclear."}
{"id": "PMID:30682", "title": "Secretion pattern of secretin in man: regulation by gastric acid.", "content": "Median concentration of plasma secretin in the fasting state in 11 achlorhydria patients, 17 normal subjects, eight duodenal ulcer patients, and 11 Zollinger-Ellison patients was 0.3, 1.2, 2.5, and 5.9 pmol x 1(-1), respectively. Aspiration of gastric acid normal subjects and duodenal ulcer patients was followed by a significant lowering of the plasma secretin concentration. In normal subjects insulin-induced hypoglycaemia resulted in increased secretin levels when gastric acid was allowed to enter the duodenum, whereas no changes were observed when gastric acid was aspirated. Simultaneous measurements of intraduodenal pH and plasma secretin concentration in the fasting state and in response to a meal showed that rapid falls in intraduodenal pH were followed by short-lived increments in plasma secretin concentration. These changes in pH and in secretin levels were diminished after cimetidine. It is concluded that gastric acid in man does trigger release of secretin and that secretin is secreted intermittently both in the fasting state and in response to a meal when boluses of acid enter the duodenum.", "contents": "Secretion pattern of secretin in man: regulation by gastric acid. Median concentration of plasma secretin in the fasting state in 11 achlorhydria patients, 17 normal subjects, eight duodenal ulcer patients, and 11 Zollinger-Ellison patients was 0.3, 1.2, 2.5, and 5.9 pmol x 1(-1), respectively. Aspiration of gastric acid normal subjects and duodenal ulcer patients was followed by a significant lowering of the plasma secretin concentration. In normal subjects insulin-induced hypoglycaemia resulted in increased secretin levels when gastric acid was allowed to enter the duodenum, whereas no changes were observed when gastric acid was aspirated. Simultaneous measurements of intraduodenal pH and plasma secretin concentration in the fasting state and in response to a meal showed that rapid falls in intraduodenal pH were followed by short-lived increments in plasma secretin concentration. These changes in pH and in secretin levels were diminished after cimetidine. It is concluded that gastric acid in man does trigger release of secretin and that secretin is secreted intermittently both in the fasting state and in response to a meal when boluses of acid enter the duodenum."}
{"id": "PMID:30683", "title": "Short chain fatty acid absorption by the human large intestine.", "content": "Short chain fatty acid absorption from the human rectum has been studied in 46 subjects attending an obesity clinic, using a dialysis bag technique. From a mixed electrolyte solution, acetate concentrations fell from 97.0 to 64.2 mmol/l, and sodium from 97.8 to 85.1 mmol/l with respective net absorption rates of 8.1 and 5.2 mumol/cm2/h. From a solution with mixed short chain fatty acids acetate concentration fell from 62.3 to 37.6 mmol/l, propionate from 20.2 to 11.5 mmol/l, and butyrate from 25.7 to 17.3 mmol/l with absorption rates of 5.2, 1.8, and 1.9 mumol/cm2/h. Lowering pH from 7.2 to 5.5, to test the possibility that absorption occurred by passive non-ionic diffusion, had no effect on absorption rates, although pH rose rapidly in the dialysis fluid. These results are comparable with rates of acetate absorption from the animal large intestine. The hypothesis that short chain fatty acids are not absorbed from the large gut and therefore contribute to faecal bulk by retaining water in the bowel lumen may need revision.", "contents": "Short chain fatty acid absorption by the human large intestine. Short chain fatty acid absorption from the human rectum has been studied in 46 subjects attending an obesity clinic, using a dialysis bag technique. From a mixed electrolyte solution, acetate concentrations fell from 97.0 to 64.2 mmol/l, and sodium from 97.8 to 85.1 mmol/l with respective net absorption rates of 8.1 and 5.2 mumol/cm2/h. From a solution with mixed short chain fatty acids acetate concentration fell from 62.3 to 37.6 mmol/l, propionate from 20.2 to 11.5 mmol/l, and butyrate from 25.7 to 17.3 mmol/l with absorption rates of 5.2, 1.8, and 1.9 mumol/cm2/h. Lowering pH from 7.2 to 5.5, to test the possibility that absorption occurred by passive non-ionic diffusion, had no effect on absorption rates, although pH rose rapidly in the dialysis fluid. These results are comparable with rates of acetate absorption from the animal large intestine. The hypothesis that short chain fatty acids are not absorbed from the large gut and therefore contribute to faecal bulk by retaining water in the bowel lumen may need revision."}
{"id": "PMID:30684", "title": "The effect of streptozotocin analogues on guanylate cyclase activity.", "content": "Streptozotocin, a nitrosamide carcinogen, enhances the activity of guanylate cyclase. Six analogues of streptozotocin were studied in order to elucidate critical structure-activity relationships pertaining to the activation of guanylate cyclase. Analogue 1, known as chlorozotocin, has a nitroso group and increased guanylate cyclase activity 17 to 28-fold. Analogue III, which also has a nitroso group, but greater structural modifications with 4 acetate groups extending off of the glucose moiety, activated guanylate cyclase in colon but not in kidney. The other analogues (II,IV,VI, and VIII) lacking nitroso groups, either had no effect or produced mild decreases in guanylate cyclase activity.", "contents": "The effect of streptozotocin analogues on guanylate cyclase activity. Streptozotocin, a nitrosamide carcinogen, enhances the activity of guanylate cyclase. Six analogues of streptozotocin were studied in order to elucidate critical structure-activity relationships pertaining to the activation of guanylate cyclase. Analogue 1, known as chlorozotocin, has a nitroso group and increased guanylate cyclase activity 17 to 28-fold. Analogue III, which also has a nitroso group, but greater structural modifications with 4 acetate groups extending off of the glucose moiety, activated guanylate cyclase in colon but not in kidney. The other analogues (II,IV,VI, and VIII) lacking nitroso groups, either had no effect or produced mild decreases in guanylate cyclase activity."}
{"id": "PMID:30685", "title": "Reconstitution of rabbit muscle aldolase after dissociation and denaturation at alkaline pH.", "content": "Tetrameric rabbit muscle aldolase is dissociated to the inactive monomer at strongly alkaline pH (pH greater than or equal to 12). As shown by sedimentation velocity, fluorescence emission, and specific activity, the final profiles of dissociation, denaturation, and deactivation run parallel. Increasing incubation time proves the enzyme to be metastable in the pH range of deactivation. At 10 less than pH less than 12 \"hysteresis\" of the deactivation-reactivation reaction is observed. Short incubation at pH greater than or equal to 12 leads to high yields of reactivation (greater than or equal to 60%), while irreversibly denatured enzyme protein is the final product after long incubation. The kinetics of reconstitution under essentially irreversible conditions (pH 7.6) can be described by a sequential uni-bimolecular mechanism, assuming partial activity of the isolated subunits. The kinetic constants correspond to those observed for the reactivation after denaturation at acid pH or in 6M guanidine. HCl. Obviously the pH-dependent deactivation and reactivation of aldolase at alkaline pH obeys the general transconformation/association model which has been previously reported to hold for the reconstitution of numerous oligomeric enzymes after denaturation in various denaturants.", "contents": "Reconstitution of rabbit muscle aldolase after dissociation and denaturation at alkaline pH. Tetrameric rabbit muscle aldolase is dissociated to the inactive monomer at strongly alkaline pH (pH greater than or equal to 12). As shown by sedimentation velocity, fluorescence emission, and specific activity, the final profiles of dissociation, denaturation, and deactivation run parallel. Increasing incubation time proves the enzyme to be metastable in the pH range of deactivation. At 10 less than pH less than 12 \"hysteresis\" of the deactivation-reactivation reaction is observed. Short incubation at pH greater than or equal to 12 leads to high yields of reactivation (greater than or equal to 60%), while irreversibly denatured enzyme protein is the final product after long incubation. The kinetics of reconstitution under essentially irreversible conditions (pH 7.6) can be described by a sequential uni-bimolecular mechanism, assuming partial activity of the isolated subunits. The kinetic constants correspond to those observed for the reactivation after denaturation at acid pH or in 6M guanidine. HCl. Obviously the pH-dependent deactivation and reactivation of aldolase at alkaline pH obeys the general transconformation/association model which has been previously reported to hold for the reconstitution of numerous oligomeric enzymes after denaturation in various denaturants."}
{"id": "PMID:30690", "title": "Nucleotides and coenzymes in nuclei isolated from rat liver.", "content": "In rat-liver nuclei, isolated by the non-aqueous technique, the concentrations and labelling rates of the purine moiety of acid-soluble nucleotides were determined and compared with corresponding data for non-fractionated tissue and nuclei-free cytoplasm. Livers were used from untreated rats, from rats with a highly stimulated synthesis of NAD and from rats following a heavy metabolic load with adenosine. Under all circumstances, the nuclear and cytoplasmic concentrations of nucleotides (e.g. ATP and its dephosphorylated forms, pyridine nucleotides) and of free glucose were practically identical. Specific radioactivities after a pulse with formate also indicated a nucleo-cytoplasmic equilibrium for purine-containing nucleotides. It is concluded that precursor pools for nuclear biosyntheses as well as energy supply for other nuclear activities may be determined by an analysis of the non-fractionated tissue.", "contents": "Nucleotides and coenzymes in nuclei isolated from rat liver. In rat-liver nuclei, isolated by the non-aqueous technique, the concentrations and labelling rates of the purine moiety of acid-soluble nucleotides were determined and compared with corresponding data for non-fractionated tissue and nuclei-free cytoplasm. Livers were used from untreated rats, from rats with a highly stimulated synthesis of NAD and from rats following a heavy metabolic load with adenosine. Under all circumstances, the nuclear and cytoplasmic concentrations of nucleotides (e.g. ATP and its dephosphorylated forms, pyridine nucleotides) and of free glucose were practically identical. Specific radioactivities after a pulse with formate also indicated a nucleo-cytoplasmic equilibrium for purine-containing nucleotides. It is concluded that precursor pools for nuclear biosyntheses as well as energy supply for other nuclear activities may be determined by an analysis of the non-fractionated tissue."}
{"id": "PMID:30691", "title": "Kawasaki disease: a 'new' pediatric enigma.", "content": "More than 250 cases of this puzzling illness, first described in Japan a decade ago, have now been reported in the United States. The etiology, epidemiology, and true incidence remain to be determined. But since some 2% of victims develop severe cardiac complications and some may die suddenly months after apparent complete recovery, pediatricians must now consider this entity in the differential diagnosis of protracted, febrile illness.", "contents": "Kawasaki disease: a 'new' pediatric enigma. More than 250 cases of this puzzling illness, first described in Japan a decade ago, have now been reported in the United States. The etiology, epidemiology, and true incidence remain to be determined. But since some 2% of victims develop severe cardiac complications and some may die suddenly months after apparent complete recovery, pediatricians must now consider this entity in the differential diagnosis of protracted, febrile illness."}
{"id": "PMID:30692", "title": "Endocrine pancreatic tumors.", "content": "The pathology and cell biology of endocrine pancreatic tumors are reviewed. It is probable that all these tumors are \"functioning\" in the sense that they elaborate hormones that cause more or less conspicuous clinical syndromes. Identification of such secretory products is essential for an optimal diagnosis, localization, treatment, and follow-up. Recent data indicate that endocrine pancreatic tumors evolve from progenitor cells of ducts. This histogenetic mechanism may explain the occurrence not only of mixed or multihormonal tumors but also of tumors producing hormones that are absent from the adult human pancreas. In addition to their clinically apparent effects, many endocrine pancreatic tumors affect the surrounding endocrine pancreas in a characteristic way. The mechanisms behind and the potential diagnostic usefulness of these changes are discussed.", "contents": "Endocrine pancreatic tumors. The pathology and cell biology of endocrine pancreatic tumors are reviewed. It is probable that all these tumors are \"functioning\" in the sense that they elaborate hormones that cause more or less conspicuous clinical syndromes. Identification of such secretory products is essential for an optimal diagnosis, localization, treatment, and follow-up. Recent data indicate that endocrine pancreatic tumors evolve from progenitor cells of ducts. This histogenetic mechanism may explain the occurrence not only of mixed or multihormonal tumors but also of tumors producing hormones that are absent from the adult human pancreas. In addition to their clinically apparent effects, many endocrine pancreatic tumors affect the surrounding endocrine pancreas in a characteristic way. The mechanisms behind and the potential diagnostic usefulness of these changes are discussed."}
{"id": "PMID:30694", "title": "Further characterization of Mycobacterium ulcerans toxin.", "content": "Mycobacterium ulcerans produces an exotoxin in culture which, when inoculated into guinea pig skin, causes inflammation, necrosis, edema, and other histopathological changes resembling those in infections of humans. The toxin was resistant to heat and to alkalies and was moderately acid labile. Toxic activity was destroyed by Pronase, phospholipase, lipase, amylase, and glucosidase but not by trypsin, collagenase, cellulase, lysozyme, hyaluronidase, or neuraminidase. Toxic activity was resistant to treatment with 2-mercaptoethanol, urea, guanidine hydrochloride, p-chloromercuribenzoate, ethylenediaminetetraacetate, and sodium deoxycholate but was destroyed by sodium m-periodate and sodium dodecyl sulfate. The toxin was precipitated by a wide range of ammonium sulfate concentrations. Extraction with chlorofrom-methanol or petroleum ether destroyed its activity. Isopycnic density gradient ultracentrifugation in KBr produced a high-density lipoprotein layer with a 24-fold increase in specific activity. The results indicate that this toxin is a high-molecular-weight phospholipoprotein-polysaccharide complex.", "contents": "Further characterization of Mycobacterium ulcerans toxin. Mycobacterium ulcerans produces an exotoxin in culture which, when inoculated into guinea pig skin, causes inflammation, necrosis, edema, and other histopathological changes resembling those in infections of humans. The toxin was resistant to heat and to alkalies and was moderately acid labile. Toxic activity was destroyed by Pronase, phospholipase, lipase, amylase, and glucosidase but not by trypsin, collagenase, cellulase, lysozyme, hyaluronidase, or neuraminidase. Toxic activity was resistant to treatment with 2-mercaptoethanol, urea, guanidine hydrochloride, p-chloromercuribenzoate, ethylenediaminetetraacetate, and sodium deoxycholate but was destroyed by sodium m-periodate and sodium dodecyl sulfate. The toxin was precipitated by a wide range of ammonium sulfate concentrations. Extraction with chlorofrom-methanol or petroleum ether destroyed its activity. Isopycnic density gradient ultracentrifugation in KBr produced a high-density lipoprotein layer with a 24-fold increase in specific activity. The results indicate that this toxin is a high-molecular-weight phospholipoprotein-polysaccharide complex."}
{"id": "PMID:30695", "title": "Lactate dehydrogenase mutants of Streptococcus mutans: isolation and preliminary characterization.", "content": "Mutants of Streptococcus mutans were isolated which lack the enzyme activity L (+)-lactate dehydrogenase. Reversion studies indicate that the genetic defects are in the structural gene for the enzyme. The mutants produce less titratable acid from glucose, adhere better to hydroxyapatite, and accumulate more plaque when grown in the presence of sucrose than does the parent strain. These findings suggest a possible use for the mutants as effector strains in the replacement therapy of dental caries.", "contents": "Lactate dehydrogenase mutants of Streptococcus mutans: isolation and preliminary characterization. Mutants of Streptococcus mutans were isolated which lack the enzyme activity L (+)-lactate dehydrogenase. Reversion studies indicate that the genetic defects are in the structural gene for the enzyme. The mutants produce less titratable acid from glucose, adhere better to hydroxyapatite, and accumulate more plaque when grown in the presence of sucrose than does the parent strain. These findings suggest a possible use for the mutants as effector strains in the replacement therapy of dental caries."}
{"id": "PMID:30696", "title": "Effects of surface-active agents on neutrophil receptors.", "content": "An easily performed assay to identify the C3b and Fc receptors on human neutrophils was developed. Salmonella typhimurium were treated with fluorescein and then incubated in nonimmune fresh human serum, which led to C3b fixation via activation of the alternative pathway. Similarly, type II pneumococci were treated with fluorescein and opsonized with type-specific rabbit antiserum. Neutrophils bearing C3b and Fc receptors formed rosettes with the respective bacteria, which were easily readable because of their bright fluorescence. Incubation of neutrophils at 37 degrees C with C3-coated bacteria generated 54 +/ 4% C3b rosettes, whereas neutrophils incubated with immunoglobulin G-coated bacteria yielded 75 +/ 7% rosettes. Incubation at 4 degrees C inhibited the formation of C3b rosettes but not Fc rosettes. Heat inactivation of the fresh human serum at 56 degrees C for 30 min completely inhibited the formation of the C3b rosettes, and addition of heat-aggregated immunoglobulin G to the polymorphonuclear leukocyte blocked the ability of the polymorphonuclear leukocyte to bind immunoglobulin G-coated bacteria. Addition of 1.0 mM N-ethylmaleimide, 0.1 mg of trypsin per ml, 10 mM H2O2, O2- generated by xanthine-xanthine oxidase, and 8 times 10(-4) M hydrocortisone inhibited the C3b receptor, but did not inhibit the Fc receptor. In neutrophils, the selective effect of the various inhibitors suggests that the Fc and C3b receptors are distinct entities.", "contents": "Effects of surface-active agents on neutrophil receptors. An easily performed assay to identify the C3b and Fc receptors on human neutrophils was developed. Salmonella typhimurium were treated with fluorescein and then incubated in nonimmune fresh human serum, which led to C3b fixation via activation of the alternative pathway. Similarly, type II pneumococci were treated with fluorescein and opsonized with type-specific rabbit antiserum. Neutrophils bearing C3b and Fc receptors formed rosettes with the respective bacteria, which were easily readable because of their bright fluorescence. Incubation of neutrophils at 37 degrees C with C3-coated bacteria generated 54 +/ 4% C3b rosettes, whereas neutrophils incubated with immunoglobulin G-coated bacteria yielded 75 +/ 7% rosettes. Incubation at 4 degrees C inhibited the formation of C3b rosettes but not Fc rosettes. Heat inactivation of the fresh human serum at 56 degrees C for 30 min completely inhibited the formation of the C3b rosettes, and addition of heat-aggregated immunoglobulin G to the polymorphonuclear leukocyte blocked the ability of the polymorphonuclear leukocyte to bind immunoglobulin G-coated bacteria. Addition of 1.0 mM N-ethylmaleimide, 0.1 mg of trypsin per ml, 10 mM H2O2, O2- generated by xanthine-xanthine oxidase, and 8 times 10(-4) M hydrocortisone inhibited the C3b receptor, but did not inhibit the Fc receptor. In neutrophils, the selective effect of the various inhibitors suggests that the Fc and C3b receptors are distinct entities."}
{"id": "PMID:30697", "title": "Protective ability of Salmonella ribosomal protein and RNA in inbred mice.", "content": "Ribosomal vaccines prepared from Salmonella typhimurium were effective immunogens in A/J, C3H/HeDub, and C3H/HeJ mice. Purified ribosomal components were also tested as immunogens in the inbred mice. Protein isolated from a Salmonella ribosomal fraction could protect all three mouse strains. Although purified RNA was shown to be protective for A/J and C3H/HeDub mice, it was not protective for C3H/HeJ mice. Protective immunity could be induced in A/J and C3H/HeDub mice by various immunostimulants. Immunity in C3H/HeJ mice, however, could only be induced by Salmonella ribosomes or protein isolated from the Salmonella ribosomal fraction.", "contents": "Protective ability of Salmonella ribosomal protein and RNA in inbred mice. Ribosomal vaccines prepared from Salmonella typhimurium were effective immunogens in A/J, C3H/HeDub, and C3H/HeJ mice. Purified ribosomal components were also tested as immunogens in the inbred mice. Protein isolated from a Salmonella ribosomal fraction could protect all three mouse strains. Although purified RNA was shown to be protective for A/J and C3H/HeDub mice, it was not protective for C3H/HeJ mice. Protective immunity could be induced in A/J and C3H/HeDub mice by various immunostimulants. Immunity in C3H/HeJ mice, however, could only be induced by Salmonella ribosomes or protein isolated from the Salmonella ribosomal fraction."}
{"id": "PMID:30698", "title": "Characteristics of an adenovirus type 19 conjunctivitis isolate and evidence for a subgroup associated with epidemic conjunctivitis.", "content": "Although adneovirus type 19 (Ad19) was first described in 1955, this virus was not associated with disease until its isolation from outbreaks of conjunctivitis in 1973. A strain of Ad19 isolated from a case of conjunctivitis in Seattle in 1974 was compared with the reference strain (3911). Plaque number and size were enhanced by 30 mM MgCl2. Low pH and chloroform treatment had no effect on either strain's activity, but the two strains were sensitive to pH 8. Growth curves were characteristic of adenoviruses, but differences were seen in the amount of virus released. The ratios of particles to plaque-forming units (approximately 10,000:1) were similar for both. Both virus preparations contained high concentrations of group-specific complement-fixing antigen. Cross-reactions were seen by hemagglutination inhibition and immunoelectron microscopy between antisera to Ad8, Ad9, and Ad10 versus both strains of Ad19, but were not seen by neutralization. We would like to suggest, based on exclusive conjunctivitis association and cross-reactions, that the four cross-reacting serotypes, Ad8, Ad9, Ad10, and Ad19, represent a subgroup of adenoviruses specfically associated with conjunctivitis.", "contents": "Characteristics of an adenovirus type 19 conjunctivitis isolate and evidence for a subgroup associated with epidemic conjunctivitis. Although adneovirus type 19 (Ad19) was first described in 1955, this virus was not associated with disease until its isolation from outbreaks of conjunctivitis in 1973. A strain of Ad19 isolated from a case of conjunctivitis in Seattle in 1974 was compared with the reference strain (3911). Plaque number and size were enhanced by 30 mM MgCl2. Low pH and chloroform treatment had no effect on either strain's activity, but the two strains were sensitive to pH 8. Growth curves were characteristic of adenoviruses, but differences were seen in the amount of virus released. The ratios of particles to plaque-forming units (approximately 10,000:1) were similar for both. Both virus preparations contained high concentrations of group-specific complement-fixing antigen. Cross-reactions were seen by hemagglutination inhibition and immunoelectron microscopy between antisera to Ad8, Ad9, and Ad10 versus both strains of Ad19, but were not seen by neutralization. We would like to suggest, based on exclusive conjunctivitis association and cross-reactions, that the four cross-reacting serotypes, Ad8, Ad9, Ad10, and Ad19, represent a subgroup of adenoviruses specfically associated with conjunctivitis."}
{"id": "PMID:30699", "title": "Effect of pH on the growth and glucose metabolism of Neisseria gonorrhoeae.", "content": "This study examined the effect of pH on the metabolism of glucose by Neisseria gonorrhoeae. Radiorespirometric studies revealed that cells growing at pH 7.2 or 8.0 metabolized glucose primarily (ca. 80%) via the Entner-Doudoroff pathway. The remainder of the glucose was metabolized via the pentose phosphate pathway (ca. 20%). The tricarboxylic acid cycle was not active during glucose catabolism at either pH 7.2 or 8.0, and acetate accumulated in the medium. Cells growing at pH 6.0 had markedly increased pentose phosphate pathway activity (ca. 50%) and a functioning tricarboxylic acid cycle. The alteration in pathways was not due to differences in growth rate, but to the pH of the medium. Chemical fractionation of labeled cells and total hexose analyses revealed that growth pH markedly affected the composition of the gonococcus.", "contents": "Effect of pH on the growth and glucose metabolism of Neisseria gonorrhoeae. This study examined the effect of pH on the metabolism of glucose by Neisseria gonorrhoeae. Radiorespirometric studies revealed that cells growing at pH 7.2 or 8.0 metabolized glucose primarily (ca. 80%) via the Entner-Doudoroff pathway. The remainder of the glucose was metabolized via the pentose phosphate pathway (ca. 20%). The tricarboxylic acid cycle was not active during glucose catabolism at either pH 7.2 or 8.0, and acetate accumulated in the medium. Cells growing at pH 6.0 had markedly increased pentose phosphate pathway activity (ca. 50%) and a functioning tricarboxylic acid cycle. The alteration in pathways was not due to differences in growth rate, but to the pH of the medium. Chemical fractionation of labeled cells and total hexose analyses revealed that growth pH markedly affected the composition of the gonococcus."}
{"id": "PMID:30700", "title": "Factors affecting the aggregation of Actinomyces naeslundii during growth and in washed cell suspensions.", "content": "Various factors affecting the aggregation of Actinomyces naeslundii strain 12104 were studied. When the pH of glucose-supplemented growth medium fell below 5.5, the cells aggregated and formed microbial masses which tenaciously adhered to the culture vessels. When the organism was cultured in the same medium in the absence of glucose, maximum growth was reduced and the final culture pH values remained above 6.5, but the cells were more dispersed and nonadherent. Adjusting the final pH of these cultures to below 5.5 with HCl caused the cells to aggregate. Cells from unsupplemented cultures with final pH values of 6.7 were washed by centrifugation, dispersed by vigorous shaking, and suspended in buffer at pH values ranging from 4.5 to 8.0. Aggregation (expressed as the percent reduction of optical density at 520 nm after incubation at 37 degrees C) occurred rapidly at pH values below 6.0 but did not readily occur at higher pH values. Aggregation of strain 12104 in washed cell suspensions was induced by low pH and influenced by cell concentration and ionic strength of the environment. Low pH values also induced aggregation in washed cell suspensions of Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius, and Actinomyces viscosus.", "contents": "Factors affecting the aggregation of Actinomyces naeslundii during growth and in washed cell suspensions. Various factors affecting the aggregation of Actinomyces naeslundii strain 12104 were studied. When the pH of glucose-supplemented growth medium fell below 5.5, the cells aggregated and formed microbial masses which tenaciously adhered to the culture vessels. When the organism was cultured in the same medium in the absence of glucose, maximum growth was reduced and the final culture pH values remained above 6.5, but the cells were more dispersed and nonadherent. Adjusting the final pH of these cultures to below 5.5 with HCl caused the cells to aggregate. Cells from unsupplemented cultures with final pH values of 6.7 were washed by centrifugation, dispersed by vigorous shaking, and suspended in buffer at pH values ranging from 4.5 to 8.0. Aggregation (expressed as the percent reduction of optical density at 520 nm after incubation at 37 degrees C) occurred rapidly at pH values below 6.0 but did not readily occur at higher pH values. Aggregation of strain 12104 in washed cell suspensions was induced by low pH and influenced by cell concentration and ionic strength of the environment. Low pH values also induced aggregation in washed cell suspensions of Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius, and Actinomyces viscosus."}
{"id": "PMID:30701", "title": "Mechanism of coaggregation between Actinomyces viscosus T14V and Streptococcus sanguis 34.", "content": "Actinomyces viscosus T14V and Streptococcus sanguis 34 coaggregate by a mechanism which is not inhibited by 1 M NaCl, is dextran independent, requires calcium, is pH dependent with an optimum at pH 8.0 to 8.5, and appears to require the interaction of a protein or glycoprotein on A. viscosus with a carbohydrate on S. sanguis. The coaggregation is inhibited more than 80% by 0.01 M lactose, 0.02 M beta-methyl-D-galactoside, or 0.05 M D-galactose; inhibition of coaggregation was less than 10% in 0.1 M alpha-methyl-D-galactoside, melibiose, maltose, cellobiose, sucrose, and a number of monosaccharides. At very high concentrations of enzyme, protease from S. griseus destroyed the reactive site on A. viscosus but not on S. sanguis. Both were totally resistant to dextranase. Periodate (0.01 M; pH 4) inactivated both bacteria. The ability of S. sanguis to coaggregate with A. viscosus was not destroyed by phenol-water extraction at 65 degrees C for 15 min. When the bacteria were cultured under specified conditions, the coaggregation was highly reproducible. Under the same conditions, T14AV, the avirulent mutant of A. viscosus T14V, did not coaggregate with S. sanguis 34. Electron microscopic studies of coaggregates, labeled immunochemically with antibody to A. viscosus, indicated that fibrils on A. viscosus may be involved in the coaggregation.", "contents": "Mechanism of coaggregation between Actinomyces viscosus T14V and Streptococcus sanguis 34. Actinomyces viscosus T14V and Streptococcus sanguis 34 coaggregate by a mechanism which is not inhibited by 1 M NaCl, is dextran independent, requires calcium, is pH dependent with an optimum at pH 8.0 to 8.5, and appears to require the interaction of a protein or glycoprotein on A. viscosus with a carbohydrate on S. sanguis. The coaggregation is inhibited more than 80% by 0.01 M lactose, 0.02 M beta-methyl-D-galactoside, or 0.05 M D-galactose; inhibition of coaggregation was less than 10% in 0.1 M alpha-methyl-D-galactoside, melibiose, maltose, cellobiose, sucrose, and a number of monosaccharides. At very high concentrations of enzyme, protease from S. griseus destroyed the reactive site on A. viscosus but not on S. sanguis. Both were totally resistant to dextranase. Periodate (0.01 M; pH 4) inactivated both bacteria. The ability of S. sanguis to coaggregate with A. viscosus was not destroyed by phenol-water extraction at 65 degrees C for 15 min. When the bacteria were cultured under specified conditions, the coaggregation was highly reproducible. Under the same conditions, T14AV, the avirulent mutant of A. viscosus T14V, did not coaggregate with S. sanguis 34. Electron microscopic studies of coaggregates, labeled immunochemically with antibody to A. viscosus, indicated that fibrils on A. viscosus may be involved in the coaggregation."}
{"id": "PMID:30704", "title": "A simple method of screening for antisperm antibodies in the human male. Detection of spermatozoal surface IgG with the direct mixed antiglobulin reaction carried out on untreated fresh human semen.", "content": "A simple and rapid test for the detection of antisperm antibodies of the IgG class on freely swimming spermatozoa in fresh human semen is described. The test is based on the formation of motile mixed agglutinates between erythrocytes sensitized with incomplete anti-Rh-antibodies and freely swimming spermatozoa with surface antisperm antibodies, after mixing both cell types together with anti-IgG antiserum. Agglutination of the red blood cells serves as an internal control. The test can be applied on ejaculates with spermatozoa concentrations down to one million per ml, provided the motility is sufficient. The percentage of motile spermatozoa found to be coated with antisperm antibodies of the IgG class, and the extent of the coating, proved to be correlated with the agglutination titer of circulating antisperm antibodies and with the inhibition of sperm penetration into cervical mucus. The test can be used as a screening for the presence of antisperm autoantibodies in serum and semen.", "contents": "A simple method of screening for antisperm antibodies in the human male. Detection of spermatozoal surface IgG with the direct mixed antiglobulin reaction carried out on untreated fresh human semen. A simple and rapid test for the detection of antisperm antibodies of the IgG class on freely swimming spermatozoa in fresh human semen is described. The test is based on the formation of motile mixed agglutinates between erythrocytes sensitized with incomplete anti-Rh-antibodies and freely swimming spermatozoa with surface antisperm antibodies, after mixing both cell types together with anti-IgG antiserum. Agglutination of the red blood cells serves as an internal control. The test can be applied on ejaculates with spermatozoa concentrations down to one million per ml, provided the motility is sufficient. The percentage of motile spermatozoa found to be coated with antisperm antibodies of the IgG class, and the extent of the coating, proved to be correlated with the agglutination titer of circulating antisperm antibodies and with the inhibition of sperm penetration into cervical mucus. The test can be used as a screening for the presence of antisperm autoantibodies in serum and semen."}
{"id": "PMID:30706", "title": "Effect of endogenous and exogenous progesterone on human endometrial enzymes.", "content": "Activities of 9 enzymes were determined biochemically in the endometrium. In Trial I (five women) 25 mg progesterone were injected i.m. on day 9 of the cycle; and endometrial biopsy taken 24 hours later was compared with endometrium from day 10 and day 21, taken in two untreated cycles from the same volunteers. Similarly, in Trial II (five women) 50 mg progesterone were injected on day 9, biopsy taken on day 11 and compared with days 11 and 21 from untreated cycles. The specific activites of lactate dehydrogenase, isocitrate dehydrogenase (ICDH), malate dehydrogenase, glutamate dehydrogenase, beta-glucuronidase, acid phosphatase (ACP) and alkaline phosphatase (AP) were significantly higher in the secretory phase. Twenty-five milligrams progesterone (after 24 hours) caused increases of some enzymes, significant only for AP. Fifty milligrams (after 48 hours) increased significantly the activity of ICDH and ACP. Biochemical changes, especially increase of ICDH, can be used for detection of the effect of progesterone on the endometrium.", "contents": "Effect of endogenous and exogenous progesterone on human endometrial enzymes. Activities of 9 enzymes were determined biochemically in the endometrium. In Trial I (five women) 25 mg progesterone were injected i.m. on day 9 of the cycle; and endometrial biopsy taken 24 hours later was compared with endometrium from day 10 and day 21, taken in two untreated cycles from the same volunteers. Similarly, in Trial II (five women) 50 mg progesterone were injected on day 9, biopsy taken on day 11 and compared with days 11 and 21 from untreated cycles. The specific activites of lactate dehydrogenase, isocitrate dehydrogenase (ICDH), malate dehydrogenase, glutamate dehydrogenase, beta-glucuronidase, acid phosphatase (ACP) and alkaline phosphatase (AP) were significantly higher in the secretory phase. Twenty-five milligrams progesterone (after 24 hours) caused increases of some enzymes, significant only for AP. Fifty milligrams (after 48 hours) increased significantly the activity of ICDH and ACP. Biochemical changes, especially increase of ICDH, can be used for detection of the effect of progesterone on the endometrium."}
{"id": "PMID:30707", "title": "The effect of antibody against a purified sperm-coating antigen on human sperm.", "content": "A purified fraction of human seminal plasma containing a sperm-coating antigen and two minor contaminants was used to immunize rabbits by intravenous route. An antiserum containing only the antibody against the sperm-coating antigen as examined by immunoelectrophoresis was obtained from one rabbit. The effect of this antiserum on human sperm was examined by sperm-immobilization and sperm-agglutination tests. The results revealed that the antibody against the purified sperm-coating antigen was incapable of immobilzing or agglutinating human sperm. This indicates that the purified sperm-coating antigen is unlikely to be useful as an antifertility antigen for immunologic fertility control.", "contents": "The effect of antibody against a purified sperm-coating antigen on human sperm. A purified fraction of human seminal plasma containing a sperm-coating antigen and two minor contaminants was used to immunize rabbits by intravenous route. An antiserum containing only the antibody against the sperm-coating antigen as examined by immunoelectrophoresis was obtained from one rabbit. The effect of this antiserum on human sperm was examined by sperm-immobilization and sperm-agglutination tests. The results revealed that the antibody against the purified sperm-coating antigen was incapable of immobilzing or agglutinating human sperm. This indicates that the purified sperm-coating antigen is unlikely to be useful as an antifertility antigen for immunologic fertility control."}
{"id": "PMID:30708", "title": "An improved assay technique for the proteolytic activity of individual human spermatozoa.", "content": "An improved substrate-film technique has been developed for the assay of released proteinase from individual human spermatozoa. During the preparation of the thin gelatin membrane, it is pretreated with formaldehyde and NaOH. These agents alter the plasma membrane and the outer acrosomal membrane of the spermatozoon, facilitating the release of acrosomal enzymes. This effect is further enhanced by the addition of albumin to the incubation mixture. More than 90% of the spermatozoa in a normal ejaculate give a reaction by this method. It reaches a maximum after 4 hours of incubation and does not increase further even up to 12 hours. No difference in the reaction between washed and unwashed ejaculated spermatozoa can be found. The nature of the proteolytic activity and its possible significance in infertility are discussed.", "contents": "An improved assay technique for the proteolytic activity of individual human spermatozoa. An improved substrate-film technique has been developed for the assay of released proteinase from individual human spermatozoa. During the preparation of the thin gelatin membrane, it is pretreated with formaldehyde and NaOH. These agents alter the plasma membrane and the outer acrosomal membrane of the spermatozoon, facilitating the release of acrosomal enzymes. This effect is further enhanced by the addition of albumin to the incubation mixture. More than 90% of the spermatozoa in a normal ejaculate give a reaction by this method. It reaches a maximum after 4 hours of incubation and does not increase further even up to 12 hours. No difference in the reaction between washed and unwashed ejaculated spermatozoa can be found. The nature of the proteolytic activity and its possible significance in infertility are discussed."}
{"id": "PMID:30709", "title": "Effect of medroxyprogesterone acetate contraception on cytoplasmic estrogen receptor content of the human cervix uteri.", "content": "Specimens of cervical tissue from five women each on 150 mg and 450 mg regimens of medroxyprogesterone acetate (MPA) for contraceptive purposes, were obtained through punch biopsy 15 days after injection. In another group of five women each on the same contraceptive regimens, punch biopsies of the cervix uteri were obtained 30 days after injection. These times corresponded to maximum and optimum blood levels of MPA respectively. Corresponding tissue from the same anatomical position in patients matched, where possible, for age and parity was obtained from hysterectomy specimens to serve as controls. Quantification of estrogen receptor content in the cytoplasm of these tissues was achieved through standard procedures. Analysis of data showed that MPA suppressed estrogen receptor content significantly compared to controls, but that there were no differences in this effect between the two dosages or time of biopsy.", "contents": "Effect of medroxyprogesterone acetate contraception on cytoplasmic estrogen receptor content of the human cervix uteri. Specimens of cervical tissue from five women each on 150 mg and 450 mg regimens of medroxyprogesterone acetate (MPA) for contraceptive purposes, were obtained through punch biopsy 15 days after injection. In another group of five women each on the same contraceptive regimens, punch biopsies of the cervix uteri were obtained 30 days after injection. These times corresponded to maximum and optimum blood levels of MPA respectively. Corresponding tissue from the same anatomical position in patients matched, where possible, for age and parity was obtained from hysterectomy specimens to serve as controls. Quantification of estrogen receptor content in the cytoplasm of these tissues was achieved through standard procedures. Analysis of data showed that MPA suppressed estrogen receptor content significantly compared to controls, but that there were no differences in this effect between the two dosages or time of biopsy."}
{"id": "PMID:30711", "title": "The effect of norgestrel and clogestone on the spontaneous motility of the human fallopian tube.", "content": "Spontaneous isometric contractions in vitro of both isthmic and ampullary parts of the human fallopian tube were studied. The tubes were obtained during the early luteal phase of the menstrual cycle from patients undergoing abdominal hysterectomy and who had ingested clogestone acetate or norgestrel, either 1 or 12 hours prior to the experiment. A dose of 150 microgram dl-norgestrel given orally 12 hours preoperatively caused a significant increase in the frequency of spontaneous isometric contractions together with a significant reduction in the area under the curve for each contraction. The possible effect of this altered pattern of motility is discussed.", "contents": "The effect of norgestrel and clogestone on the spontaneous motility of the human fallopian tube. Spontaneous isometric contractions in vitro of both isthmic and ampullary parts of the human fallopian tube were studied. The tubes were obtained during the early luteal phase of the menstrual cycle from patients undergoing abdominal hysterectomy and who had ingested clogestone acetate or norgestrel, either 1 or 12 hours prior to the experiment. A dose of 150 microgram dl-norgestrel given orally 12 hours preoperatively caused a significant increase in the frequency of spontaneous isometric contractions together with a significant reduction in the area under the curve for each contraction. The possible effect of this altered pattern of motility is discussed."}
{"id": "PMID:30712", "title": "Lactate and pyruvate utilization by the spermatozoa of infertile human males.", "content": "In studying the metabolic pathway of lactate and pyruvate in human spermatozoa from fertile and infertile subjects, pyruvate 1-C14 and lactate 1-C14 were used as substrates in a radiorespirometry system. Spermatozoa from patients with 20 +/- 2.0/10(6) spz/ml and decreased motility (group B) showed a more active decarboxylation of both pyruvate 1-C14 and lactate 1-C14 with a higher production of lactate C14, oxaloacetate, citrate, and isocitrate than those from fertile normal subjects (group A). Spermatozoa from fertile patients with normal counts but low motility (35 +/- 2.0% +++ motility) showed a similar rate of decarboxtlation of pyruvate 1-C14 but a greater rate of decarboxylation of lactate 1-C14 than those from fertile subjects. The low utilization of pyruvate by the spermatozoa from group C infertile patients, with intermediate counts and motility could be explained by a metabolic failure similar to that produced by some inhibitors of the respiratory chain. We do not have an explanation for the metabolic behavior observed in spermatozoa from group B patients, and further research on this point is desirable.", "contents": "Lactate and pyruvate utilization by the spermatozoa of infertile human males. In studying the metabolic pathway of lactate and pyruvate in human spermatozoa from fertile and infertile subjects, pyruvate 1-C14 and lactate 1-C14 were used as substrates in a radiorespirometry system. Spermatozoa from patients with 20 +/- 2.0/10(6) spz/ml and decreased motility (group B) showed a more active decarboxylation of both pyruvate 1-C14 and lactate 1-C14 with a higher production of lactate C14, oxaloacetate, citrate, and isocitrate than those from fertile normal subjects (group A). Spermatozoa from fertile patients with normal counts but low motility (35 +/- 2.0% +++ motility) showed a similar rate of decarboxtlation of pyruvate 1-C14 but a greater rate of decarboxylation of lactate 1-C14 than those from fertile subjects. The low utilization of pyruvate by the spermatozoa from group C infertile patients, with intermediate counts and motility could be explained by a metabolic failure similar to that produced by some inhibitors of the respiratory chain. We do not have an explanation for the metabolic behavior observed in spermatozoa from group B patients, and further research on this point is desirable."}
{"id": "PMID:30713", "title": "Intrauterine device and pelvic inflammatory disease.", "content": "Using a retrospective case control design on 101 women with a first episode of acute pelvic inflammatory disease (PID), it was found that 15% were wearing an intrauterine device, as compared to 7% out of a control group of 101 women matched for age, marital status, and interval since their last pregnancy termination. No statistically significant correlation between IUD usage and PID was demonstrated. A significant correlation (P less than 0.01) between previous induced abortion and subsequent PID was found. In the PID group, a significantly higher proportion of previous abdominal and pelvic operations (P less than 0.005) was found as compared to the control group, but the numbers were small. In the absence of a higher frequency of IUD wearers among PID patients as compared with matched controls, we do not believe that there is an increased risk of pelvic inflammatory disease.", "contents": "Intrauterine device and pelvic inflammatory disease. Using a retrospective case control design on 101 women with a first episode of acute pelvic inflammatory disease (PID), it was found that 15% were wearing an intrauterine device, as compared to 7% out of a control group of 101 women matched for age, marital status, and interval since their last pregnancy termination. No statistically significant correlation between IUD usage and PID was demonstrated. A significant correlation (P less than 0.01) between previous induced abortion and subsequent PID was found. In the PID group, a significantly higher proportion of previous abdominal and pelvic operations (P less than 0.005) was found as compared to the control group, but the numbers were small. In the absence of a higher frequency of IUD wearers among PID patients as compared with matched controls, we do not believe that there is an increased risk of pelvic inflammatory disease."}
{"id": "PMID:30714", "title": "Effect of kallikrein on bull sperm motility in vitro.", "content": "The application of kallikrein--a kinin-releasing porcine pancreatic kininogenase--exerted considerable stimulation of bull sperm motility in vitro. The kallikrein was used in two concentrations: 1 and 100 KU/ml semen. Both concentrations gave similar effect: at the 4th hour of incubation at room temperature the motility rate of spermatozoa exceeded five and four times, respectively, that of the control samples. Higher penetrating ability of bull spermatozoa in cow's estral secretion was also recorded in the experimental samples treated with kallikrein in both concentrations at the 2nd and 4th hour of incubation in comparison with the controls.", "contents": "Effect of kallikrein on bull sperm motility in vitro. The application of kallikrein--a kinin-releasing porcine pancreatic kininogenase--exerted considerable stimulation of bull sperm motility in vitro. The kallikrein was used in two concentrations: 1 and 100 KU/ml semen. Both concentrations gave similar effect: at the 4th hour of incubation at room temperature the motility rate of spermatozoa exceeded five and four times, respectively, that of the control samples. Higher penetrating ability of bull spermatozoa in cow's estral secretion was also recorded in the experimental samples treated with kallikrein in both concentrations at the 2nd and 4th hour of incubation in comparison with the controls."}
{"id": "PMID:30715", "title": "Serum and seminal plasma prolactin levels in oligospermia.", "content": "Prolactin concentration was estimated by radioimmunoassay in seminal plasma and serum of 26 oligospermic and 23 normospermic men. No significant difference was found in the mean serum prolactin concentration between normospermic and oligospermic subjects, but there was an inverse correlation between serum prolactin level and sperm count within the group of oligospermic patients. Although the mean prolactin concentration in seminal plasma of oligospermic group was somewhat lower than in the normospermic group the difference did not reach statistical significance, and no correlation was found between seminal plasma prolactin concentration and sperm count within either group.", "contents": "Serum and seminal plasma prolactin levels in oligospermia. Prolactin concentration was estimated by radioimmunoassay in seminal plasma and serum of 26 oligospermic and 23 normospermic men. No significant difference was found in the mean serum prolactin concentration between normospermic and oligospermic subjects, but there was an inverse correlation between serum prolactin level and sperm count within the group of oligospermic patients. Although the mean prolactin concentration in seminal plasma of oligospermic group was somewhat lower than in the normospermic group the difference did not reach statistical significance, and no correlation was found between seminal plasma prolactin concentration and sperm count within either group."}
{"id": "PMID:30716", "title": "A simple ambulatory method for removal of occult IUDs.", "content": "With the increased popularity of the IUD as a contraceptive method, there is a rise in the cases of occult IUDs as a result of the disappearance of the threads from the vagina. Our experience has shown that in the cases where the marker is missing, but the IUD is in the uterine cavity, it can be easily removed by using the Novak curette. This procedure spares the patients general anesthesia, D & C, and unnecessary hospitalization with its expenses.", "contents": "A simple ambulatory method for removal of occult IUDs. With the increased popularity of the IUD as a contraceptive method, there is a rise in the cases of occult IUDs as a result of the disappearance of the threads from the vagina. Our experience has shown that in the cases where the marker is missing, but the IUD is in the uterine cavity, it can be easily removed by using the Novak curette. This procedure spares the patients general anesthesia, D & C, and unnecessary hospitalization with its expenses."}
{"id": "PMID:30717", "title": "Pure crystalline estradiol pellet implantation for contraception.", "content": "The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.", "contents": "Pure crystalline estradiol pellet implantation for contraception. The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients."}
{"id": "PMID:30718", "title": "Definition of period of induction of deciduoma in the rat using ornithine decarboxylase as a marker of growth onset.", "content": "The activity of uterine ornithine decarboxylase (ODC) was measured during the 24 hours after systemic induction of decidualization. Following a latent period of 2.5 hours, activity rose and reached a peak of 5.6 +/- 1.1 fold at 5 hours after induction. The activity then declined and a second, lower peak was seen at 21 hours. The increase in ODC activity was suppressed by treatment with cycloheximide (50 mg/kg) and dactinomycin, 500 microgram/rat, confirming that the enzyme response reflects protein synthesis. The increase and the base-line level of ODC activity were suppressed by ergocornine pretreatment (1 mg/rat) which disturbs the endocrine balance of pseudopregnancy. It was concluded that the growth and differentiation of decidual tissue began 2.5 hours after application of the induction stimulus.", "contents": "Definition of period of induction of deciduoma in the rat using ornithine decarboxylase as a marker of growth onset. The activity of uterine ornithine decarboxylase (ODC) was measured during the 24 hours after systemic induction of decidualization. Following a latent period of 2.5 hours, activity rose and reached a peak of 5.6 +/- 1.1 fold at 5 hours after induction. The activity then declined and a second, lower peak was seen at 21 hours. The increase in ODC activity was suppressed by treatment with cycloheximide (50 mg/kg) and dactinomycin, 500 microgram/rat, confirming that the enzyme response reflects protein synthesis. The increase and the base-line level of ODC activity were suppressed by ergocornine pretreatment (1 mg/rat) which disturbs the endocrine balance of pseudopregnancy. It was concluded that the growth and differentiation of decidual tissue began 2.5 hours after application of the induction stimulus."}
{"id": "PMID:30719", "title": "Electrophoretic patterns of total, nuclear, and flagellar proteins from ejaculated human spermatozoa.", "content": "By means of selective solubilization methods and slab gel electrophoresis, reproducible patterns of 19, 37, and 56 protein bands were found to be associated with nuclear, \"flagellar,\" and total human spermatozoa, respectively. Forty protein bands were found between the molecular weight of 12,400 to 160,000 daltons. Twelve bands were associated with values lower than 12,400 daltons. The nuclear major bands were located in a low molecular weight zone, while \"flagellar\" ones were located in a high molecular weight zone. None of these bands represents degradation products since a) in the solubilized samples neither acrosin, chymotrypsin, nor trypsin activities were present, b) in the presence of two protease inhibitors the same electrophoretic patterns were observed, and c) labelled globins added during sample manipulation were quantitatively recovered without degradation.", "contents": "Electrophoretic patterns of total, nuclear, and flagellar proteins from ejaculated human spermatozoa. By means of selective solubilization methods and slab gel electrophoresis, reproducible patterns of 19, 37, and 56 protein bands were found to be associated with nuclear, \"flagellar,\" and total human spermatozoa, respectively. Forty protein bands were found between the molecular weight of 12,400 to 160,000 daltons. Twelve bands were associated with values lower than 12,400 daltons. The nuclear major bands were located in a low molecular weight zone, while \"flagellar\" ones were located in a high molecular weight zone. None of these bands represents degradation products since a) in the solubilized samples neither acrosin, chymotrypsin, nor trypsin activities were present, b) in the presence of two protease inhibitors the same electrophoretic patterns were observed, and c) labelled globins added during sample manipulation were quantitatively recovered without degradation."}
{"id": "PMID:30720", "title": "Conservative correction of uterine anomalies in cases of congenital and posttraumatic infertility.", "content": "Uterine anomalies are due either to primary congenital malformations, or to secondary traumatic lesions of the intrauterine cavity as well as to pathology of the endometrium. The latter two etiologic factors create difficulties in the correct diagnosis of a congenital malformation and despite the convincing hysterosalpingographic findings a false diagnosis of a congenital malformation and despite the convincing hysterosalpingographic findings a false diagnosis is frequent. On the other hand the various degrees of uterine anomalies cannot always convince the gynecologist to undertake a plastic operation where the results for future fertility are doubtful. In our experience the extensive beneficial use of a variety of selected IUDs for the correction of intrauterine lesions also resulted in the correction of the size and shape of the uteri, previously diagnosed as malformed. The preliminary results of treatment in 110 cases of uterine anomalies after the application of a selected IUD combined with the administration of high doses of gestagens, showed an overall satisfactory improvement or complete reconstruction to a normal uterus in 86 (78%) of the cases. Higher fertility rate, better pregnancy outcome, correct diagnosis of the existing malformation, and safer decisions for further correction have also been attributed to the beneficial effects of the above treatment.", "contents": "Conservative correction of uterine anomalies in cases of congenital and posttraumatic infertility. Uterine anomalies are due either to primary congenital malformations, or to secondary traumatic lesions of the intrauterine cavity as well as to pathology of the endometrium. The latter two etiologic factors create difficulties in the correct diagnosis of a congenital malformation and despite the convincing hysterosalpingographic findings a false diagnosis of a congenital malformation and despite the convincing hysterosalpingographic findings a false diagnosis is frequent. On the other hand the various degrees of uterine anomalies cannot always convince the gynecologist to undertake a plastic operation where the results for future fertility are doubtful. In our experience the extensive beneficial use of a variety of selected IUDs for the correction of intrauterine lesions also resulted in the correction of the size and shape of the uteri, previously diagnosed as malformed. The preliminary results of treatment in 110 cases of uterine anomalies after the application of a selected IUD combined with the administration of high doses of gestagens, showed an overall satisfactory improvement or complete reconstruction to a normal uterus in 86 (78%) of the cases. Higher fertility rate, better pregnancy outcome, correct diagnosis of the existing malformation, and safer decisions for further correction have also been attributed to the beneficial effects of the above treatment."}
{"id": "PMID:30721", "title": "Studies on biochemical characteristics of an early decidual protein.", "content": "Previous work in our laboratory has demonstrated the specific synthesis of a soluble protein (A) in the rat endometrium on day L4 of pseudopregnancy 1 h after the decidual induction; the A protein synthesis being higher in the antimesometrial region (AMR) than in the mesometrial one. We have now examined in the AMR of rat endometria on day L4 of pseudopregnancy: 1) the effect of cycloheximide (500 microgram, i.p. 30 min before decidual induction) on the biosynthesis of the A protein, and 2) the effect of actinomycin D (Act. D) (5 microgram/uterine horn 60 min before the decidual stimulation) on the induction of A protein synthesis. The synthesis of the A protein was determined by acrylamide gel electrophoresis of endometrial soluble proteins after double-labeling incorporation of amino acids. Results showed that: 1) the cycloheximide inhibited the synthesis of the A protein which indicates a de novo protein synthesis; 2) the Act. D inhibited the A synthesis suggesting that synthesis of an Act. D-sensitive product is one of the earliest macromolecular synthetic events after decidual induction.", "contents": "Studies on biochemical characteristics of an early decidual protein. Previous work in our laboratory has demonstrated the specific synthesis of a soluble protein (A) in the rat endometrium on day L4 of pseudopregnancy 1 h after the decidual induction; the A protein synthesis being higher in the antimesometrial region (AMR) than in the mesometrial one. We have now examined in the AMR of rat endometria on day L4 of pseudopregnancy: 1) the effect of cycloheximide (500 microgram, i.p. 30 min before decidual induction) on the biosynthesis of the A protein, and 2) the effect of actinomycin D (Act. D) (5 microgram/uterine horn 60 min before the decidual stimulation) on the induction of A protein synthesis. The synthesis of the A protein was determined by acrylamide gel electrophoresis of endometrial soluble proteins after double-labeling incorporation of amino acids. Results showed that: 1) the cycloheximide inhibited the synthesis of the A protein which indicates a de novo protein synthesis; 2) the Act. D inhibited the A synthesis suggesting that synthesis of an Act. D-sensitive product is one of the earliest macromolecular synthetic events after decidual induction."}
{"id": "PMID:30722", "title": "Release rate of testosterone and estrogens from polydimethylsiloxane implants for extended periods in vivo compared with loss in vitro.", "content": "Release rates of testosterone, estrone, and estradiol placed in chambers made from polydimethylsiloxane (PDS) tubing (Dow Corning \"Silastic,\" 3.35 mm ID x 4.65 mm OD) were studied in 14 freemartin cattle with minimal or non-detectable endogenous hormone secretion, and in 0.9% saline:methanol (1:1) baths shaken at 38 degree C. Eighty-seven implants, varying in length from 2 to 10 cm, were placed in 14 animals for 27 to 235 days. The average release rates +/- standard errors, in microgram/cm/day, were testosterone, 55.9 +/- 2.4, estrone, 12.6 +/- 1.8, and estradiol, 11.1 +/- 1.1. A relatively constant release rate was found over the period of time studied and sufficient steroid remained for potential release over periods exceeding 1 year. The dose of hormone delivered was sufficient to increase mounting activity in testosterone-treated animals and estrual activity in those receiving estrogens. Corresponding release rates in vitro for four 10-cm implants containing either testosterone, estrone, or estradiol were 94.3 +/- 1.9, 15.5 +/- 0.7, and 12.7 +/- 0.6 microgram/cm/day, respectively. The general magnitude of release rate in animals could be predicted from laboratory tests.", "contents": "Release rate of testosterone and estrogens from polydimethylsiloxane implants for extended periods in vivo compared with loss in vitro. Release rates of testosterone, estrone, and estradiol placed in chambers made from polydimethylsiloxane (PDS) tubing (Dow Corning \"Silastic,\" 3.35 mm ID x 4.65 mm OD) were studied in 14 freemartin cattle with minimal or non-detectable endogenous hormone secretion, and in 0.9% saline:methanol (1:1) baths shaken at 38 degree C. Eighty-seven implants, varying in length from 2 to 10 cm, were placed in 14 animals for 27 to 235 days. The average release rates +/- standard errors, in microgram/cm/day, were testosterone, 55.9 +/- 2.4, estrone, 12.6 +/- 1.8, and estradiol, 11.1 +/- 1.1. A relatively constant release rate was found over the period of time studied and sufficient steroid remained for potential release over periods exceeding 1 year. The dose of hormone delivered was sufficient to increase mounting activity in testosterone-treated animals and estrual activity in those receiving estrogens. Corresponding release rates in vitro for four 10-cm implants containing either testosterone, estrone, or estradiol were 94.3 +/- 1.9, 15.5 +/- 0.7, and 12.7 +/- 0.6 microgram/cm/day, respectively. The general magnitude of release rate in animals could be predicted from laboratory tests."}
{"id": "PMID:30727", "title": "Reversible sterilization.", "content": "The present techniques for sterilization of women consist of different methods to block the passage through the oviducts. The disadvantage of all techniques is that the possiblity of restoring fertility is very limited. The aim of the present study is to demonstrate a method of sterilization which is reversible.", "contents": "Reversible sterilization. The present techniques for sterilization of women consist of different methods to block the passage through the oviducts. The disadvantage of all techniques is that the possiblity of restoring fertility is very limited. The aim of the present study is to demonstrate a method of sterilization which is reversible."}
{"id": "PMID:30728", "title": "The characterisation of thawed semen, and the timing and route of insemination associated with conception in the human.", "content": "The temporal and qualitative aspects of the conceptual process of a small number of pregnancies achieved by donor insemination have been analysed to understand the semen values required and the optimal insemination timing and route.", "contents": "The characterisation of thawed semen, and the timing and route of insemination associated with conception in the human. The temporal and qualitative aspects of the conceptual process of a small number of pregnancies achieved by donor insemination have been analysed to understand the semen values required and the optimal insemination timing and route."}
{"id": "PMID:30729", "title": "The anti-reproductive pharmacology of LH-RH and agonistic analogues.", "content": "LH-RH and three particular (\"super\") analogues were evaluated for agonistic (ovulation-induction and short-term uterotrophic properties) and  postcoital contraceptive activity in rodents. Additionally, LH-RH and/or a representative analogue (D-Ala6-des Gly10-Pro9-LH-RH ethylamide) were tested for postcoital contraceptive/vaginal smear/return to fertility effects, precoital contraceptive activity, and effects on puberty in the immature female. All compounds induced ovulation and uterotrophic effects and terminated pregnancy when administered either pre- or post-implantation. LH-RH and the representative analogue, while terminating pregnancy postcoitally, produced an associated break in the characteristic leucocytic vaginal smear of pregnancy to one of cornification by day 12; at this time mating and insemination were reestablished and all rats carried to normal term. Precoitally, LH-RH administered to nembutalized (but not to unblocked) rats produced a 50% reduction in the pregnancy rate and a 38% decrease in the number of viable pups delivered. In immature rats, the representative analogue delayed puberty (i.e. vaginal canalization) and retarded the growth of the ovaries, uteri, and anterior pituitary gland. The collective data strongly support the concept that LH-RH and agonistic derivatives, in spite of their putative pro-fertility classification, are characteristically antifertility by nature. Since the latter effect appears to be the paradoxically dominant one, it is suggested that LH-RH agonism is synonymous with contraception. Furthermore, such peptides may represent a new potential approach to fertility control.", "contents": "The anti-reproductive pharmacology of LH-RH and agonistic analogues. LH-RH and three particular (\"super\") analogues were evaluated for agonistic (ovulation-induction and short-term uterotrophic properties) and  postcoital contraceptive activity in rodents. Additionally, LH-RH and/or a representative analogue (D-Ala6-des Gly10-Pro9-LH-RH ethylamide) were tested for postcoital contraceptive/vaginal smear/return to fertility effects, precoital contraceptive activity, and effects on puberty in the immature female. All compounds induced ovulation and uterotrophic effects and terminated pregnancy when administered either pre- or post-implantation. LH-RH and the representative analogue, while terminating pregnancy postcoitally, produced an associated break in the characteristic leucocytic vaginal smear of pregnancy to one of cornification by day 12; at this time mating and insemination were reestablished and all rats carried to normal term. Precoitally, LH-RH administered to nembutalized (but not to unblocked) rats produced a 50% reduction in the pregnancy rate and a 38% decrease in the number of viable pups delivered. In immature rats, the representative analogue delayed puberty (i.e. vaginal canalization) and retarded the growth of the ovaries, uteri, and anterior pituitary gland. The collective data strongly support the concept that LH-RH and agonistic derivatives, in spite of their putative pro-fertility classification, are characteristically antifertility by nature. Since the latter effect appears to be the paradoxically dominant one, it is suggested that LH-RH agonism is synonymous with contraception. Furthermore, such peptides may represent a new potential approach to fertility control."}
{"id": "PMID:30730", "title": "The effect of ovarian wedge resection and incision on circulating gonadotropin in patients with polycystic ovarian disease.", "content": "Wedge resection (WR) was performed in 12 women with polycystic ovarian disease (PCOD), and Incision was done in 4 PCOD patients without any resection of ovarian tissue. Serum LH, FSH, estradiol-17beta (E2), progesterone, and urinary 17 ketosteroid (17KS) were measured serially before and after surgery. Neither WR nor Incision had any effect on FSH levels. Serum LH levels which had been hypergonadotropic preoperatively, became markedly lower 7--14 days after surgery in 12 wedge-resected and 2 incised patients. Within 7 days after WR there was a significant fall of E2 and a decrease of 17KS. In addition to those hormonal changes observed after WR, BBT charts turned out to be diphasic after the oral administration of dydrogesterone (Duphaston) in 12 out of 17 PCOD patients. The present data suggest that the reduction of the serum LH, induced by an interaction between the ovarian steroidogenesis and the suprapituitary mechanisms, might be involved in the occurrence of ovulation after WR in PCOD patients.", "contents": "The effect of ovarian wedge resection and incision on circulating gonadotropin in patients with polycystic ovarian disease. Wedge resection (WR) was performed in 12 women with polycystic ovarian disease (PCOD), and Incision was done in 4 PCOD patients without any resection of ovarian tissue. Serum LH, FSH, estradiol-17beta (E2), progesterone, and urinary 17 ketosteroid (17KS) were measured serially before and after surgery. Neither WR nor Incision had any effect on FSH levels. Serum LH levels which had been hypergonadotropic preoperatively, became markedly lower 7--14 days after surgery in 12 wedge-resected and 2 incised patients. Within 7 days after WR there was a significant fall of E2 and a decrease of 17KS. In addition to those hormonal changes observed after WR, BBT charts turned out to be diphasic after the oral administration of dydrogesterone (Duphaston) in 12 out of 17 PCOD patients. The present data suggest that the reduction of the serum LH, induced by an interaction between the ovarian steroidogenesis and the suprapituitary mechanisms, might be involved in the occurrence of ovulation after WR in PCOD patients."}
{"id": "PMID:30732", "title": "Pharmacological treatment of obesity.", "content": "Obesity results when the ingestion of energy exceeds its utilization, leading to an excessive expansion of the adipose tissue mass. Current pharmacological therapy for the obese patient focuses primarily on reducing energy intake. Anorectic agents reduce food consumption by modifying central systems in the brain which are involved in appetite regulation. These agents are reviewed in terms of mechanism of action, and clinical safety and efficacy in suppressing appetite and promoting weight loss. Newer anorectic agents which are being evaluated currently in clinical and animal studies are described. Clinical assessments of therapeutic regimens utilizing the thyroid hormones and human chorionic gonadotropin are evaluated. Finally, an overview of novel pharmacological approaches to the treatment of obesity is presented.", "contents": "Pharmacological treatment of obesity. Obesity results when the ingestion of energy exceeds its utilization, leading to an excessive expansion of the adipose tissue mass. Current pharmacological therapy for the obese patient focuses primarily on reducing energy intake. Anorectic agents reduce food consumption by modifying central systems in the brain which are involved in appetite regulation. These agents are reviewed in terms of mechanism of action, and clinical safety and efficacy in suppressing appetite and promoting weight loss. Newer anorectic agents which are being evaluated currently in clinical and animal studies are described. Clinical assessments of therapeutic regimens utilizing the thyroid hormones and human chorionic gonadotropin are evaluated. Finally, an overview of novel pharmacological approaches to the treatment of obesity is presented."}
{"id": "PMID:30734", "title": "The antimicrobial activity of urine of paraplegic patients receiving methenamine mandelate.", "content": "The antimicrobial activity of urine collected from adult male paraplegics ingesting methenamine mandelate (MM) was evaluated. The in vitro bacterial growth in urine from these patients was inhibited when the free formaldehyde (HCHO) concentration was 10 to 22 microgram per ml. When the HCHO concentration was in the region of 28 microgram per ml or greater, bactericidal effect became apparent. Urine containing 1323 microgram of MM per ml with a pH of 5.9 when freshly voided had sufficient HCHO to be bacteriostatic. Urine containing at least 1740 microgram of MM per ml with a pH of 5.1 or less when freshly voided was bactericidal. The latter concentration of MM in urine was usually achieved when the patient ingested 4 g of MM per day in divided doses and the intake of fluid was not excessive. Under some circumstances an individual receiving MM without an additional acidifying agent may produce urine with a pH low enough to release sufficient HCHO to exert a useful antibacterial effect. However, supplementary acidification with ammonium chloride produced marked lowering of the urinary pH in all patients receiving MM, resulting in bactericidal levels of HCHO.", "contents": "The antimicrobial activity of urine of paraplegic patients receiving methenamine mandelate. The antimicrobial activity of urine collected from adult male paraplegics ingesting methenamine mandelate (MM) was evaluated. The in vitro bacterial growth in urine from these patients was inhibited when the free formaldehyde (HCHO) concentration was 10 to 22 microgram per ml. When the HCHO concentration was in the region of 28 microgram per ml or greater, bactericidal effect became apparent. Urine containing 1323 microgram of MM per ml with a pH of 5.9 when freshly voided had sufficient HCHO to be bacteriostatic. Urine containing at least 1740 microgram of MM per ml with a pH of 5.1 or less when freshly voided was bactericidal. The latter concentration of MM in urine was usually achieved when the patient ingested 4 g of MM per day in divided doses and the intake of fluid was not excessive. Under some circumstances an individual receiving MM without an additional acidifying agent may produce urine with a pH low enough to release sufficient HCHO to exert a useful antibacterial effect. However, supplementary acidification with ammonium chloride produced marked lowering of the urinary pH in all patients receiving MM, resulting in bactericidal levels of HCHO."}
{"id": "PMID:30735", "title": "Bladder surface mucin. Examination of possible mechanisms for its antibacterial effect.", "content": "We have previusly provided physiologic and histochemical data implicating the bladder surface mucin layer as an important new antibacterial defense mechanism. This mucin or its contents seems to act as an \"antiadherence factor\", inhibiting bacterial adherence to the bladder mucosa and thereby facilitating the removal of bacteria by the voiding process. The present study was designed to investigate three mechanisms by which the mucin might repel bacterial attachment. Our data suggest that neither IgA nor a chelating agent are anti-adherence factors. We did find, however, that pH had a significant effect on the adherence of bacteria to mucosal cells stripped of their mucin layer. This result suggest that electrochemical charge is important in bacterial adherence. We beleive that the mucin layer both provides an electrochemical coat on the bladder surface that is a poor substrate for bacterial adherence and blocks the receptor sites of the transitional cells to which the microbes might adhere.", "contents": "Bladder surface mucin. Examination of possible mechanisms for its antibacterial effect. We have previusly provided physiologic and histochemical data implicating the bladder surface mucin layer as an important new antibacterial defense mechanism. This mucin or its contents seems to act as an \"antiadherence factor\", inhibiting bacterial adherence to the bladder mucosa and thereby facilitating the removal of bacteria by the voiding process. The present study was designed to investigate three mechanisms by which the mucin might repel bacterial attachment. Our data suggest that neither IgA nor a chelating agent are anti-adherence factors. We did find, however, that pH had a significant effect on the adherence of bacteria to mucosal cells stripped of their mucin layer. This result suggest that electrochemical charge is important in bacterial adherence. We beleive that the mucin layer both provides an electrochemical coat on the bladder surface that is a poor substrate for bacterial adherence and blocks the receptor sites of the transitional cells to which the microbes might adhere."}
{"id": "PMID:30733", "title": "Direct and reflex myocardial effects of intracoronary administered contrast materials in the anesthetized and conscious dog: comparison of standard and newer contrast materials.", "content": "The direct and indirect actions on left ventricular dynamics of contrast material (sodium meglumine diatrizoate) currently used for coronary arteriography, modified ionic material (sodium meglumine calcium metrizoate) and non-ionic material (metrizamide) were assessed in conscious and anesthetized dogs. In both anesthetized and conscious animals, the diatrizoate compound caused an early (3--10 sec after injection) decrease in peak dp/dt and dp/dt/LVP40, followed by late (10--20 sec after injection) increases in these variables. The predominant early and later effects of the calcium metrizoate compound were increases in parameters of LV contractile state. Metrizamide produced no significant early alterations, but later induced a small increase in these variables. The positive inotropic actions of each of the contrast materials were attenuated by beta adrenergic blockade. The early effects of the contrast materials were similar in the presence of segmental ischemia. The late positive inotropic effects in response to the diatrizoate compound and metrizamide were not observed in the ischemic state, while the positive inotropic response induced by the calcium metrizoate compound was significantly reduced. Thus intracoronary administration of sodium meglumine diatrizoate produced direct myocardial depression, followed by adrenergically mediated myocardial stimulation. Calcium metrizoate caused prominent direct and adrenergically mediated augmentation in contractile state. Metrizamide induced the least alteration in LV contractile state.", "contents": "Direct and reflex myocardial effects of intracoronary administered contrast materials in the anesthetized and conscious dog: comparison of standard and newer contrast materials. The direct and indirect actions on left ventricular dynamics of contrast material (sodium meglumine diatrizoate) currently used for coronary arteriography, modified ionic material (sodium meglumine calcium metrizoate) and non-ionic material (metrizamide) were assessed in conscious and anesthetized dogs. In both anesthetized and conscious animals, the diatrizoate compound caused an early (3--10 sec after injection) decrease in peak dp/dt and dp/dt/LVP40, followed by late (10--20 sec after injection) increases in these variables. The predominant early and later effects of the calcium metrizoate compound were increases in parameters of LV contractile state. Metrizamide produced no significant early alterations, but later induced a small increase in these variables. The positive inotropic actions of each of the contrast materials were attenuated by beta adrenergic blockade. The early effects of the contrast materials were similar in the presence of segmental ischemia. The late positive inotropic effects in response to the diatrizoate compound and metrizamide were not observed in the ischemic state, while the positive inotropic response induced by the calcium metrizoate compound was significantly reduced. Thus intracoronary administration of sodium meglumine diatrizoate produced direct myocardial depression, followed by adrenergically mediated myocardial stimulation. Calcium metrizoate caused prominent direct and adrenergically mediated augmentation in contractile state. Metrizamide induced the least alteration in LV contractile state."}
{"id": "PMID:30738", "title": "[The hypertrophic obstructive cardiomyopathy (HOCM) of the newborn].", "content": "A case of a newborn infant with clinical and angiocardiographic signs of hypertrophic obstructive cardiomyopathy (HOCM) is presented. The baby died after a short therapy with beta-blockers. Light- and electron-microscopic investigations showed severe disorganization of muscular cellular arrangement and disturbances of intracellular structures of the interventricular septum. HOCM is a genetically determined disease which can present clinically in the newborn period and may simulate congenital cardiac malformations.", "contents": "[The hypertrophic obstructive cardiomyopathy (HOCM) of the newborn]. A case of a newborn infant with clinical and angiocardiographic signs of hypertrophic obstructive cardiomyopathy (HOCM) is presented. The baby died after a short therapy with beta-blockers. Light- and electron-microscopic investigations showed severe disorganization of muscular cellular arrangement and disturbances of intracellular structures of the interventricular septum. HOCM is a genetically determined disease which can present clinically in the newborn period and may simulate congenital cardiac malformations."}
{"id": "PMID:30739", "title": "The effect of atebrine and an acridine analog (BCMA) on the coenzyme fluorescence spectra of cultured melanoma and Ehrlich ascites (EL2) cells.", "content": "Coenzyme fluorescence spectra of single living cells are due to free pyridine nucleotides (folded configuration), bound pyridine nucleotides (unfolded configuration) and a third component, possibly a mixture or flavins. Such spectra can be used to recognize possible differences in coenzyme composition between cell lines or changes of metabolic pathways due to chemicals acting at levels below or above cytotoxicity, by high resolution spectrofluorometry. A study of spectra recorded from cultured Ehrlich ascites (EL2), and Harding Passey melanoma cells (HPM-67 and HPM-73 line) grown under comparable conditions, shows that free NAD(P)H predominates in HPM-67 and EL2, while this coenzyme is bound in HPM-73. The free/bound ratio may be profoundly modifed by chemicals, e.g. in the HPM-73 increase of free and decrease of bound NAD(P)H occurred upon treatment with 10(-6) oligomycin. When atebrine at levels (10(-6) M) below cytotoxicity was added, there was a decrease of the free NAD(P)H spectrum possibly through energy transfer from NAD(P)H to atebrine. Consideration of long range energy transfer i.e., excitation of atebrine by fluorescence of NAD(P)H vs. short range transfer of excitation energy from free NAD(P)H to atebrine, favors the latter mechanism. A transient (reversible) increase in atebrine fluorescence is seen following intracellular microinjection of substrate (e.g. glucose-6-P) leading to an increase in free NAD(P)H. At cytotoxic levels of atebrine (e.g 2 x 10(-5) M) an irreversible increase of atebrine fluorescence is seen. The microspectrofluorometric technique appears therefore well suited to study physiological processes at the level of intracellular coenzymes, as well as possible processes of intermolecular energy transfer in the microenvironment.", "contents": "The effect of atebrine and an acridine analog (BCMA) on the coenzyme fluorescence spectra of cultured melanoma and Ehrlich ascites (EL2) cells. Coenzyme fluorescence spectra of single living cells are due to free pyridine nucleotides (folded configuration), bound pyridine nucleotides (unfolded configuration) and a third component, possibly a mixture or flavins. Such spectra can be used to recognize possible differences in coenzyme composition between cell lines or changes of metabolic pathways due to chemicals acting at levels below or above cytotoxicity, by high resolution spectrofluorometry. A study of spectra recorded from cultured Ehrlich ascites (EL2), and Harding Passey melanoma cells (HPM-67 and HPM-73 line) grown under comparable conditions, shows that free NAD(P)H predominates in HPM-67 and EL2, while this coenzyme is bound in HPM-73. The free/bound ratio may be profoundly modifed by chemicals, e.g. in the HPM-73 increase of free and decrease of bound NAD(P)H occurred upon treatment with 10(-6) oligomycin. When atebrine at levels (10(-6) M) below cytotoxicity was added, there was a decrease of the free NAD(P)H spectrum possibly through energy transfer from NAD(P)H to atebrine. Consideration of long range energy transfer i.e., excitation of atebrine by fluorescence of NAD(P)H vs. short range transfer of excitation energy from free NAD(P)H to atebrine, favors the latter mechanism. A transient (reversible) increase in atebrine fluorescence is seen following intracellular microinjection of substrate (e.g. glucose-6-P) leading to an increase in free NAD(P)H. At cytotoxic levels of atebrine (e.g 2 x 10(-5) M) an irreversible increase of atebrine fluorescence is seen. The microspectrofluorometric technique appears therefore well suited to study physiological processes at the level of intracellular coenzymes, as well as possible processes of intermolecular energy transfer in the microenvironment."}
{"id": "PMID:30740", "title": "Dynamics of respiratory VT response to isocapnic pHa forcing in chemodenervated cats.", "content": "Arterial blood pH (pHa) was continuously monitored in decerebrate or pentobarbital-anesthetized cats with a rapidly responding hydrogen ion sensor inserted into the aorta. Alveolar carbon dioxide partial pressure and pHa were controlled independently during infusions of 1 N NaHCO3 or 0.5 N HCl into the inferior vena cava. Shifts in pHa up to 0.3 unit were effected isocapnically within 2.5-20 s over a working pHa range of 6.9-7.7. Before carotid sinus neurotomy, average onset latency of the tidal volume (VT) response to acid and alkaline pHa shifts was less than 5 S and the average VT response half time was less than 8.5 s regardless of whether the vagus nerves had been interrupted. After carotid sinus neurotomy, the deltaVT onset latency was approximately doubled, whereas the response half time was prolonged about eightfold on the average. Subsequent vagotomy tended further to increase the responding time lag. Nevertheless, the minimum response latency after peripheral chemodenervation was less than the deltapHa forcing rise time. It is concluded that the central chemoreceptors promptly sense pH change in the arterial blood and that neural processes adjust the time course of the respiratory response through the VT controller.", "contents": "Dynamics of respiratory VT response to isocapnic pHa forcing in chemodenervated cats. Arterial blood pH (pHa) was continuously monitored in decerebrate or pentobarbital-anesthetized cats with a rapidly responding hydrogen ion sensor inserted into the aorta. Alveolar carbon dioxide partial pressure and pHa were controlled independently during infusions of 1 N NaHCO3 or 0.5 N HCl into the inferior vena cava. Shifts in pHa up to 0.3 unit were effected isocapnically within 2.5-20 s over a working pHa range of 6.9-7.7. Before carotid sinus neurotomy, average onset latency of the tidal volume (VT) response to acid and alkaline pHa shifts was less than 5 S and the average VT response half time was less than 8.5 s regardless of whether the vagus nerves had been interrupted. After carotid sinus neurotomy, the deltaVT onset latency was approximately doubled, whereas the response half time was prolonged about eightfold on the average. Subsequent vagotomy tended further to increase the responding time lag. Nevertheless, the minimum response latency after peripheral chemodenervation was less than the deltapHa forcing rise time. It is concluded that the central chemoreceptors promptly sense pH change in the arterial blood and that neural processes adjust the time course of the respiratory response through the VT controller."}
{"id": "PMID:30741", "title": "Slow postcapillary changes in blood pH in vivo: titration with acetazolamide.", "content": "A stopped-flow pH electrode apparatus was used to investigate the mechanisms underlying slow changes in plasma pH (pHO) after blood leaves the pulmonary capillaries in carbonic anhydrase-inhibited animals. After acetazolamide was administered to an anesthetized dog or cat, arterial blood was withdrawn through the electrode apparatus into a syringe. Syringe movement was then suddenly stopped. Temperature and pHO of the blood in the electrode chamber were monitored both before and after blood withdrawal ceased. After stopping flow, pHO of the blood in the electrode chamber a) rose 0.02 after a dose of about 1 mg/kg acetazolamide; b) did not change after a dose of about 2 mg/kg acetazolamide; and c) fell 0.10 after a dose greater than about 5 mg/kg acetazolamide. With reasonable red cell and plasma carbonic anhydrase activities assumed for each dose level of acetazolamide, a computer model of the reaction and transport processes occurring in blood after gas exchange in the lung yielded predicted time courses of pHo that were in good agreement with the experimental results. The observed slow pHo changes are largely a result of disequilibrium of [H+] between red blood cells and plasma as blood leaves the pulmonary capillaries.", "contents": "Slow postcapillary changes in blood pH in vivo: titration with acetazolamide. A stopped-flow pH electrode apparatus was used to investigate the mechanisms underlying slow changes in plasma pH (pHO) after blood leaves the pulmonary capillaries in carbonic anhydrase-inhibited animals. After acetazolamide was administered to an anesthetized dog or cat, arterial blood was withdrawn through the electrode apparatus into a syringe. Syringe movement was then suddenly stopped. Temperature and pHO of the blood in the electrode chamber were monitored both before and after blood withdrawal ceased. After stopping flow, pHO of the blood in the electrode chamber a) rose 0.02 after a dose of about 1 mg/kg acetazolamide; b) did not change after a dose of about 2 mg/kg acetazolamide; and c) fell 0.10 after a dose greater than about 5 mg/kg acetazolamide. With reasonable red cell and plasma carbonic anhydrase activities assumed for each dose level of acetazolamide, a computer model of the reaction and transport processes occurring in blood after gas exchange in the lung yielded predicted time courses of pHo that were in good agreement with the experimental results. The observed slow pHo changes are largely a result of disequilibrium of [H+] between red blood cells and plasma as blood leaves the pulmonary capillaries."}
{"id": "PMID:30747", "title": "ATP hydrolysis and synthesis by the membrane-bound ATP synthetase complex of Methanobacterium thermoautotrophicum.", "content": "The membrane-bound ATP synthetase complex of Methanobacterium thermoautotrophicum showed maximum activity for ATP hydrolysis at pH 8, at temperatures between 65 and 70 degrees C, and at an ATP-Mg2+ ratio of 0.5. Anaerobic conditions were not prerequisite for enzyme activity. The enzyme showed a Km value for ATP of 2 mM, and activity was Mg2+ dependent; Mn2+, Co2+, Ca2+, and Zn2+ could replace Mg2+ to some extent. Other nucleoside triphosphates could be hydrolyzed. N,N'-dicyclohexylcarbodiimide inhibited ATP hydrolysis. A proton-motive force, artificially imposed by a pH shift or valinomycin, resulted in ATP synthesis in whole cells. The ATP synthetase complex of the thermophilic methanogenic bacterium is similar to those described in aerobic and anaerobic microorganisms.", "contents": "ATP hydrolysis and synthesis by the membrane-bound ATP synthetase complex of Methanobacterium thermoautotrophicum. The membrane-bound ATP synthetase complex of Methanobacterium thermoautotrophicum showed maximum activity for ATP hydrolysis at pH 8, at temperatures between 65 and 70 degrees C, and at an ATP-Mg2+ ratio of 0.5. Anaerobic conditions were not prerequisite for enzyme activity. The enzyme showed a Km value for ATP of 2 mM, and activity was Mg2+ dependent; Mn2+, Co2+, Ca2+, and Zn2+ could replace Mg2+ to some extent. Other nucleoside triphosphates could be hydrolyzed. N,N'-dicyclohexylcarbodiimide inhibited ATP hydrolysis. A proton-motive force, artificially imposed by a pH shift or valinomycin, resulted in ATP synthesis in whole cells. The ATP synthetase complex of the thermophilic methanogenic bacterium is similar to those described in aerobic and anaerobic microorganisms."}
{"id": "PMID:30748", "title": "Enchancement of streptococcal transformation yield by proteolytic enzymes.", "content": "Trypsin and other proteolytic enzymes, added together with transforming DNA or during cell-DNA contact to competent cultures of several streptococcal strains, enchanced (10 to 600%) the yield of genetic transformation (stimulation). With few exceptions, the level of stimulation was high (over 100%) when competence was low (below 2%). Stimulation was caused by the action of an enzyme on competent cells and not on any other component of transformation mixture. The phenomenon occurred when the enzyme was added to the culture not earlier than 7 min before and not later than 5 min after the period of cell-DNA contact. The presence of trypsin during cell-DNA contact caused: (i) the alterations at cell surface, demonstrated by electron microscopy, increased release of 3H-amino acid-labeled material, and higher cell susceptibility to autolysis; (ii) the increase of both total and irreversible binding of DNA by the cells; and (iii) the decrease of early nucleolytic degradation of DNA by cells. These and other data point to the importance of a delicate balance of recipient cell's surface nuclease activities in the effectiveness of transformation process. It is also possible that trypsin eliminates an unknown cellular factor which obstructs DNA-cell receptors interaction.", "contents": "Enchancement of streptococcal transformation yield by proteolytic enzymes. Trypsin and other proteolytic enzymes, added together with transforming DNA or during cell-DNA contact to competent cultures of several streptococcal strains, enchanced (10 to 600%) the yield of genetic transformation (stimulation). With few exceptions, the level of stimulation was high (over 100%) when competence was low (below 2%). Stimulation was caused by the action of an enzyme on competent cells and not on any other component of transformation mixture. The phenomenon occurred when the enzyme was added to the culture not earlier than 7 min before and not later than 5 min after the period of cell-DNA contact. The presence of trypsin during cell-DNA contact caused: (i) the alterations at cell surface, demonstrated by electron microscopy, increased release of 3H-amino acid-labeled material, and higher cell susceptibility to autolysis; (ii) the increase of both total and irreversible binding of DNA by the cells; and (iii) the decrease of early nucleolytic degradation of DNA by cells. These and other data point to the importance of a delicate balance of recipient cell's surface nuclease activities in the effectiveness of transformation process. It is also possible that trypsin eliminates an unknown cellular factor which obstructs DNA-cell receptors interaction."}
{"id": "PMID:30749", "title": "Degradation of 4-hydroxyphenylacetic acid by Trichosporon cutaneum.", "content": "Trichosporon cutaneum degraded 4-hydroxyphenylacetic acid to acetoacetic and malic acids. 3.4-Dihydroxyphenylacetic acid, an intermediate in the reaction sequence, underwent hydroxylation before the benzene ring was cleaved.", "contents": "Degradation of 4-hydroxyphenylacetic acid by Trichosporon cutaneum. Trichosporon cutaneum degraded 4-hydroxyphenylacetic acid to acetoacetic and malic acids. 3.4-Dihydroxyphenylacetic acid, an intermediate in the reaction sequence, underwent hydroxylation before the benzene ring was cleaved."}
{"id": "PMID:30750", "title": "Coordination chemistry of microbial iron transport compounds: rhodotorulic acid and iron uptake in Rhodotorula pilimanae.", "content": "The mechanism by which iron uptake is facilitated by the siderophore rhodotorulic acid (RA) in the yeast Rhodotorula pilimanae was investigated with radioactively labeled Fe and RA and kinetically inert, chromic-substituted RA complexes. The weight of the evidence supports a model in which RA mediates iron transport to the cell but does not actually transport iron into the cell. It is proposed that RA exchanges the ferric ion at the cell surface with a membrane-bound chelating agent that completes the active transport of iron into the cell. Uptake of 55Fe in ferric rhodotorulate was much more rapid than uptake of RA itself. Two exchange-inert chromic complexes of RA showed no uptake.", "contents": "Coordination chemistry of microbial iron transport compounds: rhodotorulic acid and iron uptake in Rhodotorula pilimanae. The mechanism by which iron uptake is facilitated by the siderophore rhodotorulic acid (RA) in the yeast Rhodotorula pilimanae was investigated with radioactively labeled Fe and RA and kinetically inert, chromic-substituted RA complexes. The weight of the evidence supports a model in which RA mediates iron transport to the cell but does not actually transport iron into the cell. It is proposed that RA exchanges the ferric ion at the cell surface with a membrane-bound chelating agent that completes the active transport of iron into the cell. Uptake of 55Fe in ferric rhodotorulate was much more rapid than uptake of RA itself. Two exchange-inert chromic complexes of RA showed no uptake."}
{"id": "PMID:30751", "title": "Partial purification and properties of CTP:phosphatidic acid cytidylyltransferase from membranes of Escherichia coli.", "content": "The cytosine liponucleotides CDP-diglyceride and dCDP-diglyceride are key intermediates in phospholipid biosynthesis in Escherichia coli (C. R. H. Raetz and E. P. Kennedy, J. Biol. Chem. 248:1098--1105, 1973). The enzyme responsible for their synthesis, CTP:phosphatidic acid cytidylytransferase, was solubilized from the cell envelope by a differential extraction procedure involving the detergent digitonin and was purified about 70-fold (relative to cell-free extracts) in the presence of detergent. In studies of the heat stability of the enzyme, activity decayed slowly at 63 degrees C. Initial velocity kinetic experiments suggested a sequential, rather than ping-pong, reaction mechanism; isotopic exchange reaction studies supported this conclusion and indicated that inorganic pyrophosphate is released before CDP-diglyceride in the reaction sequence. The enzyme utilized both CTP and dCTP as nucleotide substrate for the synthesis of CDP-diglyceride and dCDP-diglyceride, respectively. No distinction was observed between CTP and dCTP utilization in any of the purification, heat stability, and reaction mechanism studies. In addition, CTP and dCTP were competitive substrates for the partially purified enzyme. It therefore appears that a single enzyme catalyzes synthesis of both CDP-diglyceride and dCDP-diglyceride in E. coli. The enzyme also catalyzes a pyrophosphorolysis of CDP-diglyceride, i.e., the reverse of its physiologically important catalysis.", "contents": "Partial purification and properties of CTP:phosphatidic acid cytidylyltransferase from membranes of Escherichia coli. The cytosine liponucleotides CDP-diglyceride and dCDP-diglyceride are key intermediates in phospholipid biosynthesis in Escherichia coli (C. R. H. Raetz and E. P. Kennedy, J. Biol. Chem. 248:1098--1105, 1973). The enzyme responsible for their synthesis, CTP:phosphatidic acid cytidylytransferase, was solubilized from the cell envelope by a differential extraction procedure involving the detergent digitonin and was purified about 70-fold (relative to cell-free extracts) in the presence of detergent. In studies of the heat stability of the enzyme, activity decayed slowly at 63 degrees C. Initial velocity kinetic experiments suggested a sequential, rather than ping-pong, reaction mechanism; isotopic exchange reaction studies supported this conclusion and indicated that inorganic pyrophosphate is released before CDP-diglyceride in the reaction sequence. The enzyme utilized both CTP and dCTP as nucleotide substrate for the synthesis of CDP-diglyceride and dCDP-diglyceride, respectively. No distinction was observed between CTP and dCTP utilization in any of the purification, heat stability, and reaction mechanism studies. In addition, CTP and dCTP were competitive substrates for the partially purified enzyme. It therefore appears that a single enzyme catalyzes synthesis of both CDP-diglyceride and dCDP-diglyceride in E. coli. The enzyme also catalyzes a pyrophosphorolysis of CDP-diglyceride, i.e., the reverse of its physiologically important catalysis."}
{"id": "PMID:30752", "title": "Effects of temperature on the autolytic enzyme system of Streptococcus faecalis.", "content": "The cellular autolytic reaction system in Streptococcus faecalis ATCC 9790 was analyzed for relative increases in reaction rates with increasing temperature by determination of Arrhenius activation energies (E). The systems examined were: (i) an isolated wall-enzyme complex in 0.01 M sodium phosphate, pH 6.9; (ii) exponential-phase cells suspended in 0.01 or o.3 M sodium phosphate pH 6.8, or in 0.04 M ammonium acetate, pH 6.8, (iii) growing cultures deprived of glucose or lysine; and (iv) cultures treated in growth media with the nonionic detergent, Triton X-100. For detergent-treated cells, E values were between 23.9 and 27.4 kcal/mol (ca. 100.1 to 174.7 kJ/mol) at concentrations of Triton X-100 between about 0.03 and 0.072 mg/ml. E values dropped sharply to 11.5 to 13.0 kcal/m-l (ca. 48.2 to 54.4 kJ/mol) at Triton X-100 concentrations of 0.12 mg/ml or higher. For the remaining systems, E values ranged from 16 to 20 kcal/mol (ca. 67.0 to 83.7 kJ/mol) (wall lysis, cellular autolysis in 0.01 M sodium phosphate or in 0.04 M ammonium acetate, and autolysis of glucose-starved cells) to 31 to 38 kcal/mol (ca 129.8 to 159.1 kJ/mol) (cellular autolysis in 0.3 M sodium phosphate or autolysis of lysine-starved cells). High concentrations of Triton X-100 appear to lower the E values below the 16 to 20 kcal/mol observed for the autolysis of isolated walls. This effect may be related to disruption by the detergent of a hydrophobic complex regulating cellular autolysis in vivo.", "contents": "Effects of temperature on the autolytic enzyme system of Streptococcus faecalis. The cellular autolytic reaction system in Streptococcus faecalis ATCC 9790 was analyzed for relative increases in reaction rates with increasing temperature by determination of Arrhenius activation energies (E). The systems examined were: (i) an isolated wall-enzyme complex in 0.01 M sodium phosphate, pH 6.9; (ii) exponential-phase cells suspended in 0.01 or o.3 M sodium phosphate pH 6.8, or in 0.04 M ammonium acetate, pH 6.8, (iii) growing cultures deprived of glucose or lysine; and (iv) cultures treated in growth media with the nonionic detergent, Triton X-100. For detergent-treated cells, E values were between 23.9 and 27.4 kcal/mol (ca. 100.1 to 174.7 kJ/mol) at concentrations of Triton X-100 between about 0.03 and 0.072 mg/ml. E values dropped sharply to 11.5 to 13.0 kcal/m-l (ca. 48.2 to 54.4 kJ/mol) at Triton X-100 concentrations of 0.12 mg/ml or higher. For the remaining systems, E values ranged from 16 to 20 kcal/mol (ca. 67.0 to 83.7 kJ/mol) (wall lysis, cellular autolysis in 0.01 M sodium phosphate or in 0.04 M ammonium acetate, and autolysis of glucose-starved cells) to 31 to 38 kcal/mol (ca 129.8 to 159.1 kJ/mol) (cellular autolysis in 0.3 M sodium phosphate or autolysis of lysine-starved cells). High concentrations of Triton X-100 appear to lower the E values below the 16 to 20 kcal/mol observed for the autolysis of isolated walls. This effect may be related to disruption by the detergent of a hydrophobic complex regulating cellular autolysis in vivo."}
{"id": "PMID:30753", "title": "Transformation in pneumococcus: protein content of eclipse complex.", "content": "A two-step purification of pneumococcal eclipse complex is described, which uses sucrose gradient sedimentation followed by agarose gel permeation chromatography. Purified complex contains, in addition to donor DNA single strands, macromolecular material that can be labeled with methionine or leucine during development of competence. This material co-chromatographed with eclipse complex DNA on hydroxylapatite, was dissociated from the DNA by sodium dodecyl sulfate, and was completely digested by Pronase. The sodium dodecyl sulfate-released material eluted as a single peak in sodium dodecyl sulfate chromatography. These properties were consistent with the noncovalent association with eclipse complex of a protein or class of proteins with a narrow range of polypeptide sizes. Evidence for the specific association of this protein with transforming DNA is eclipse was also obtained from parallel purification from 35S-labeled nontransformed cells; the amount of methionine label in the corresponding fractions in such cells was only 5% of that in transformed cells.", "contents": "Transformation in pneumococcus: protein content of eclipse complex. A two-step purification of pneumococcal eclipse complex is described, which uses sucrose gradient sedimentation followed by agarose gel permeation chromatography. Purified complex contains, in addition to donor DNA single strands, macromolecular material that can be labeled with methionine or leucine during development of competence. This material co-chromatographed with eclipse complex DNA on hydroxylapatite, was dissociated from the DNA by sodium dodecyl sulfate, and was completely digested by Pronase. The sodium dodecyl sulfate-released material eluted as a single peak in sodium dodecyl sulfate chromatography. These properties were consistent with the noncovalent association with eclipse complex of a protein or class of proteins with a narrow range of polypeptide sizes. Evidence for the specific association of this protein with transforming DNA is eclipse was also obtained from parallel purification from 35S-labeled nontransformed cells; the amount of methionine label in the corresponding fractions in such cells was only 5% of that in transformed cells."}
{"id": "PMID:30754", "title": "Salmonella typhimurium LT-2 mutants with altered glutamine synthetase levels and amino acid uptake activities.", "content": "To determine whether Salmonella typhimurium has a nitrogen control response, we have examined the regulation of nitrogen utilization in two mutants with fivefold and threefold elevations in their glutamine synthetase activities. The mutants do not require glutamine for growth on glucose--ammonia medium but do have altered growth on other nitrogen sources. They grow better than an isogenic control on media containing arginine or asparate, but more slowly with proline or alanine as nitrogen sources. This unusual growth pattern is not due to altered regulation of the ammonia assimilatory enzymes, glutamate dehydrogenase and glutamate synthase, or to changes in the enzymes for aspartate degradation. However, transport for several amino acids may be affected. Measurement of amino acid uptake show that the mutants with high glutamine synthetase levels have increased rates for glutamine, arginine, aspartate, and lysine, but a decreased rate for proline. The relationship between glutamine synthetase levels and uptake  was examined in two mutants with reduced, rather than increased, glutamine synthetase production. The uptake rates for glutamine and lysine were lower in these two glutamine auxotrophs than in the Gln+ controls. These results show a correlation between the glutamine synthetase levels and the uptake rates for several amino acids. In addition, the pleiotropic growth of the mutants with elevated glutamine synthetase activities suggests that a nitrogen control response exists for S. typhimurium and that it can be altered by mutations affecting glutamine synthetase regulation.", "contents": "Salmonella typhimurium LT-2 mutants with altered glutamine synthetase levels and amino acid uptake activities. To determine whether Salmonella typhimurium has a nitrogen control response, we have examined the regulation of nitrogen utilization in two mutants with fivefold and threefold elevations in their glutamine synthetase activities. The mutants do not require glutamine for growth on glucose--ammonia medium but do have altered growth on other nitrogen sources. They grow better than an isogenic control on media containing arginine or asparate, but more slowly with proline or alanine as nitrogen sources. This unusual growth pattern is not due to altered regulation of the ammonia assimilatory enzymes, glutamate dehydrogenase and glutamate synthase, or to changes in the enzymes for aspartate degradation. However, transport for several amino acids may be affected. Measurement of amino acid uptake show that the mutants with high glutamine synthetase levels have increased rates for glutamine, arginine, aspartate, and lysine, but a decreased rate for proline. The relationship between glutamine synthetase levels and uptake  was examined in two mutants with reduced, rather than increased, glutamine synthetase production. The uptake rates for glutamine and lysine were lower in these two glutamine auxotrophs than in the Gln+ controls. These results show a correlation between the glutamine synthetase levels and the uptake rates for several amino acids. In addition, the pleiotropic growth of the mutants with elevated glutamine synthetase activities suggests that a nitrogen control response exists for S. typhimurium and that it can be altered by mutations affecting glutamine synthetase regulation."}
{"id": "PMID:30755", "title": "Benzeneboronic acid selectively inhibits sporulation of Bacillis subtilis.", "content": "m-Aminobenzeneboronic acid at levels of 0.2 mM in nutrient broth medium selectively inhibited sporulation without appreciably altering vegetative growth. Significant inhibitory effects were seen even when it was added as late as 6 h after the end of logarithmic growth. The pH changes associated with growth and sporulation of Bacillus subtilis in nutrient broth were not significantly altered by the inhibitor. When it was present in cultures of actively growing cells, its inhibitory effect could not be reversed by simple dilution. The compound caused  extensive clumping, of cells, which appeared not to be related to the ability of boronates to esterify to diols.", "contents": "Benzeneboronic acid selectively inhibits sporulation of Bacillis subtilis. m-Aminobenzeneboronic acid at levels of 0.2 mM in nutrient broth medium selectively inhibited sporulation without appreciably altering vegetative growth. Significant inhibitory effects were seen even when it was added as late as 6 h after the end of logarithmic growth. The pH changes associated with growth and sporulation of Bacillus subtilis in nutrient broth were not significantly altered by the inhibitor. When it was present in cultures of actively growing cells, its inhibitory effect could not be reversed by simple dilution. The compound caused  extensive clumping, of cells, which appeared not to be related to the ability of boronates to esterify to diols."}
{"id": "PMID:30756", "title": "Presence of Escherichia coli of a deaminase and a reductase involved in biosynthesis of riboflavin.", "content": "Two enzymes have been partially purified from extracts of Escherchia coli B which together catalyze the conversion of the product of the action of GTP cyclohydrolase II, 2,5-diamino-6-oxy-4-(5'-phosphoribosylamine)pyrimidine, to 5-amino-2,6-dioxy-4-(5'-phosphoribitylamine)pyrimidine. These two compounds are currently thought to be intermediates in the biosynthesis of riboflavin. The enzymatic conversion occurs in two steps. The product of the action of GTP cyclohydrolase II first undergoes hydrolytic deamination at carbon 2 of the ring, followed by reduction of the ribosylamino group to a ribitylamino group. The enzyme which catalyzes the first step, herein called the \"deaminase,\" has been purified 200-fold. The activity was assayed by detecting the conversion of the product of the reaction catalyzed by GTP cyclohydrolase II to a compound which reacts with butanedione to form 6,7-dimethyllumazine. The enzyme has a molecular weight of approximately 80,000 and a pH optimum of 9.1. The dephosphorylated form of the substrate is not deaminated in the presence of the enzyme. The assay for the enzyme which catalyzes the second step, referred to here as the \"reductase,\" involves the detection of the conversion of the product of the deaminase-catalyzed reaction to a compound which, after treatment with alkaline phosphatase, reacts with butanedione to form 6,7-dimethyl-8-ribityllumazine. The reductase has a molecular weight of approximately 40,000 and a pH optimum of 7.5. Like the deaminase, the reductase does not act on the dephosphorylated form of its substrate. Reduced nicotinamide adenine dinucleotide phosphate is required as a cofactor; reduced nicotinamide adenine dinucleotide can be used about 30% as well as the phosphate form. The activity of neither enzyme is inhibited by riboflavin, FMN, or flavine adenine dinucleotide.", "contents": "Presence of Escherichia coli of a deaminase and a reductase involved in biosynthesis of riboflavin. Two enzymes have been partially purified from extracts of Escherchia coli B which together catalyze the conversion of the product of the action of GTP cyclohydrolase II, 2,5-diamino-6-oxy-4-(5'-phosphoribosylamine)pyrimidine, to 5-amino-2,6-dioxy-4-(5'-phosphoribitylamine)pyrimidine. These two compounds are currently thought to be intermediates in the biosynthesis of riboflavin. The enzymatic conversion occurs in two steps. The product of the action of GTP cyclohydrolase II first undergoes hydrolytic deamination at carbon 2 of the ring, followed by reduction of the ribosylamino group to a ribitylamino group. The enzyme which catalyzes the first step, herein called the \"deaminase,\" has been purified 200-fold. The activity was assayed by detecting the conversion of the product of the reaction catalyzed by GTP cyclohydrolase II to a compound which reacts with butanedione to form 6,7-dimethyllumazine. The enzyme has a molecular weight of approximately 80,000 and a pH optimum of 9.1. The dephosphorylated form of the substrate is not deaminated in the presence of the enzyme. The assay for the enzyme which catalyzes the second step, referred to here as the \"reductase,\" involves the detection of the conversion of the product of the deaminase-catalyzed reaction to a compound which, after treatment with alkaline phosphatase, reacts with butanedione to form 6,7-dimethyl-8-ribityllumazine. The reductase has a molecular weight of approximately 40,000 and a pH optimum of 7.5. Like the deaminase, the reductase does not act on the dephosphorylated form of its substrate. Reduced nicotinamide adenine dinucleotide phosphate is required as a cofactor; reduced nicotinamide adenine dinucleotide can be used about 30% as well as the phosphate form. The activity of neither enzyme is inhibited by riboflavin, FMN, or flavine adenine dinucleotide."}
{"id": "PMID:30757", "title": "Regulation of uridylic acid biosynthesis in the cyanobacterium Anabaena variabilis.", "content": "The pathway of uridylic acid biosynthesis established by Leiberman, Kornberg, and Simms has been shown to be operative in the filamentous cyanobacterium Anabaena variabilis. The only enzyme of uridylic acid biosynthesis found to be lacking in two uracil-requiring strains of A. variabilis was aspartate transcarbamylase, the first enzyme in the pathway of de novo biosynthesis of uridvlic acid. Neither uracil-limited growth of a uracil-requiring mutant nor growth of the wild type in high concentrations of uracil resulted in substantial changes in the specific activities of enzymes of uridylic acid biosynthesis. It is therefore concluded that A. variabilis does not regulate all enzymes of this pathway by means of repression. However, control of the flow of intermediates through this pathway is possible by feedback inhibition of aspartate transcarbamylase by a variety of nucleotides.", "contents": "Regulation of uridylic acid biosynthesis in the cyanobacterium Anabaena variabilis. The pathway of uridylic acid biosynthesis established by Leiberman, Kornberg, and Simms has been shown to be operative in the filamentous cyanobacterium Anabaena variabilis. The only enzyme of uridylic acid biosynthesis found to be lacking in two uracil-requiring strains of A. variabilis was aspartate transcarbamylase, the first enzyme in the pathway of de novo biosynthesis of uridvlic acid. Neither uracil-limited growth of a uracil-requiring mutant nor growth of the wild type in high concentrations of uracil resulted in substantial changes in the specific activities of enzymes of uridylic acid biosynthesis. It is therefore concluded that A. variabilis does not regulate all enzymes of this pathway by means of repression. However, control of the flow of intermediates through this pathway is possible by feedback inhibition of aspartate transcarbamylase by a variety of nucleotides."}
{"id": "PMID:30758", "title": "Hydrolysis of phosphatidylethanolamine and phosphatidylglycerol by outer membrane phospholipase A from Acinetobacter sp. HO1-N.", "content": "An outer membrane phospholipase A active against phosphatidylglycerol and phosphatidylethanolamine was characterized from Acinetobacter sp. HO1-N.", "contents": "Hydrolysis of phosphatidylethanolamine and phosphatidylglycerol by outer membrane phospholipase A from Acinetobacter sp. HO1-N. An outer membrane phospholipase A active against phosphatidylglycerol and phosphatidylethanolamine was characterized from Acinetobacter sp. HO1-N."}
{"id": "PMID:30759", "title": "Managing tardive dyskinesia.", "content": "Tardive dyskinesia, a delayed side effect of neuroleptic drugs, requires early recognition and a systematic treatment plan. An outline is presented which offers guidelines for management strategies and drug treatments, along with a summary of recent developments.", "contents": "Managing tardive dyskinesia. Tardive dyskinesia, a delayed side effect of neuroleptic drugs, requires early recognition and a systematic treatment plan. An outline is presented which offers guidelines for management strategies and drug treatments, along with a summary of recent developments."}
{"id": "PMID:30760", "title": "Use of saliva lithium determinations for monitoring lithium therapy.", "content": "During acute and chronic administrations of lithium, 25 patients were studied to determine the effect of other psychotropic drugs on the plasma-saliva lithium concentration correlations. Changes, even discontinuation, in either tricyclic antidepressants or neuroleptics did not affect the plasma-saliva ratio which had an overall correlation coefficient of r = 0.79 (p less than 0.01). The relationship using linear regression analysis was described by the equation, y = 2.27x--0.45. Individual patients' plasma-salivary relations were described by this equation in 87% of cases. The study extends the usefulness of these determinations to include patients on lithium and neuroleptics or tricyclic antidepressants.", "contents": "Use of saliva lithium determinations for monitoring lithium therapy. During acute and chronic administrations of lithium, 25 patients were studied to determine the effect of other psychotropic drugs on the plasma-saliva lithium concentration correlations. Changes, even discontinuation, in either tricyclic antidepressants or neuroleptics did not affect the plasma-saliva ratio which had an overall correlation coefficient of r = 0.79 (p less than 0.01). The relationship using linear regression analysis was described by the equation, y = 2.27x--0.45. Individual patients' plasma-salivary relations were described by this equation in 87% of cases. The study extends the usefulness of these determinations to include patients on lithium and neuroleptics or tricyclic antidepressants."}
{"id": "PMID:30761", "title": "Comparative metabolism of lorazepam in man and four animal species.", "content": "The metabolic disposition of lorazepam (Wy-4036) in man, dog, cat, rat and miniature swine is compared. Except in the cat, absorption of lorazepam is rapid in these species. Absorption in humans is nearly complete. Lorazepam glucuronide is the major metabolite in all species except the rat in which a dihydrodiol derivative is the main product of lorazepam biotransformation. Lorazepam glucuronide, which has no demonstrable CNS activity, is also present in the plasma of all species investigated. The concentrations of lorazepam in rat brain correlate well with those in plasma but are about three times higher. The urinary route of excretion predominates in man, dog and miniature swine while in the rat the bulk of the drug-related material is eliminated with the feces as a consequence of biliary excretion.", "contents": "Comparative metabolism of lorazepam in man and four animal species. The metabolic disposition of lorazepam (Wy-4036) in man, dog, cat, rat and miniature swine is compared. Except in the cat, absorption of lorazepam is rapid in these species. Absorption in humans is nearly complete. Lorazepam glucuronide is the major metabolite in all species except the rat in which a dihydrodiol derivative is the main product of lorazepam biotransformation. Lorazepam glucuronide, which has no demonstrable CNS activity, is also present in the plasma of all species investigated. The concentrations of lorazepam in rat brain correlate well with those in plasma but are about three times higher. The urinary route of excretion predominates in man, dog and miniature swine while in the rat the bulk of the drug-related material is eliminated with the feces as a consequence of biliary excretion."}
{"id": "PMID:30762", "title": "Clinical pharmacokinetics of lorazepam: a review.", "content": "The clinical pharmacokinetics of lorazepam, a 3-hydroxy, 1,4-benzodiazepine, indicate that it is rapidly and readily absorbed, reaching peak concentrations in the blood proportional to the dose approximately 2 hours after oral administration. Blood levels decline thereafter, with an elimination half-life of about 12 hrs. Conjugation with glucuronic acid to form inactive lorazepam glucuronide is the major metabolic pathway. Seventy (70) to 75% of the administered dose is excreted as the glucuronide conjugate in the urine. On multiple-dose regimens, steady state blood levels directly proportional to the daily dose occur within 2--3 days and are maintained after several months of continuous treatment. The active drug and the glucuronide conjugate are completely eliminated from the blood within 1 week following the last dose.", "contents": "Clinical pharmacokinetics of lorazepam: a review. The clinical pharmacokinetics of lorazepam, a 3-hydroxy, 1,4-benzodiazepine, indicate that it is rapidly and readily absorbed, reaching peak concentrations in the blood proportional to the dose approximately 2 hours after oral administration. Blood levels decline thereafter, with an elimination half-life of about 12 hrs. Conjugation with glucuronic acid to form inactive lorazepam glucuronide is the major metabolic pathway. Seventy (70) to 75% of the administered dose is excreted as the glucuronide conjugate in the urine. On multiple-dose regimens, steady state blood levels directly proportional to the daily dose occur within 2--3 days and are maintained after several months of continuous treatment. The active drug and the glucuronide conjugate are completely eliminated from the blood within 1 week following the last dose."}
{"id": "PMID:30763", "title": "Clinical assessment of the safety and efficacy of lorazepam, a new benzodiazepine derivative, in the treatment of anxiety.", "content": "In a four-week double-blind study of 68 adult outpatients, lorazepam a new benzodiazepine, administered at an average total daily dosage level of 3.1 mg on a b.i.d. regimen, was clearly superior to placebo in the treatment of neurotic anxiety and its related symptoms. The lorazepam-treated group showed significantly greater improvement than the placebo-treated group (both clinically and statistically), as evidenced by the greater changes on the physician-rated Global Scale as well as by the greater changes in almost all categories on the physician-rated Hamilton Anxiety Scale and the patient-rated Lipman-Rickels 35-Item Self-Rating Scale. There were no clinically significant changes in vital signs or laboratory values and only one side effect, urinary retention (resolved without discontinuing the drug), was reported.", "contents": "Clinical assessment of the safety and efficacy of lorazepam, a new benzodiazepine derivative, in the treatment of anxiety. In a four-week double-blind study of 68 adult outpatients, lorazepam a new benzodiazepine, administered at an average total daily dosage level of 3.1 mg on a b.i.d. regimen, was clearly superior to placebo in the treatment of neurotic anxiety and its related symptoms. The lorazepam-treated group showed significantly greater improvement than the placebo-treated group (both clinically and statistically), as evidenced by the greater changes on the physician-rated Global Scale as well as by the greater changes in almost all categories on the physician-rated Hamilton Anxiety Scale and the patient-rated Lipman-Rickels 35-Item Self-Rating Scale. There were no clinically significant changes in vital signs or laboratory values and only one side effect, urinary retention (resolved without discontinuing the drug), was reported."}
{"id": "PMID:30764", "title": "Pharmacology of lorazepam.", "content": "Lorazepam reduced conflict behavior in rats and monkeys, inhibited pentylenetetrazol- and electroshock-induced convulsions, suppressed footshock-induced fighting behavior, and prevented morphine-induced stimulation in mice at lower doses than other benzodiazepines tested. This behavioral profile suggests that lorazepam will be an active anti-anxiety agent in man at low doses.", "contents": "Pharmacology of lorazepam. Lorazepam reduced conflict behavior in rats and monkeys, inhibited pentylenetetrazol- and electroshock-induced convulsions, suppressed footshock-induced fighting behavior, and prevented morphine-induced stimulation in mice at lower doses than other benzodiazepines tested. This behavioral profile suggests that lorazepam will be an active anti-anxiety agent in man at low doses."}
{"id": "PMID:30765", "title": "Studies with oral lorazepam in anxiety neurosis associated with depressive symptomatology.", "content": "Twelve studies were undertaken under a common four-week protocol to investigate the efficacy of lorazepam compared with placebo in reducing the severity of moderate to severe anxiety in 264 patients also having significant depressive symptomatology. Analysis of the results indicated that lorazepam gave generally better anxiety relief than placebo; in the majority of comparisons the differences were substantial enough to be both statistically and clinically significant. No data were obtained evidencing significant toxicity in either treatment group.", "contents": "Studies with oral lorazepam in anxiety neurosis associated with depressive symptomatology. Twelve studies were undertaken under a common four-week protocol to investigate the efficacy of lorazepam compared with placebo in reducing the severity of moderate to severe anxiety in 264 patients also having significant depressive symptomatology. Analysis of the results indicated that lorazepam gave generally better anxiety relief than placebo; in the majority of comparisons the differences were substantial enough to be both statistically and clinically significant. No data were obtained evidencing significant toxicity in either treatment group."}
{"id": "PMID:30766", "title": "Antianxiety effects of lorazepam in patients with cardiovascular symptomatology.", "content": "Lorazepam was administered to 38 patients with moderate to severe anxiety associated with cardiovascular symptomatology. A comparable group of patients on placebo (35) served as controls in this 4-week study. Average dosage was 3 mg/day given as 2 mg in the evening and 1 mg in the morning. The Global response, Hamilton Anxiety Rating Scale scores, and 35-Item Self-Rating Scale scores showed lorazepam to be significantly more effective in relieving anxiety than placebo, both clinically and statistically. Adverse reactions were transient and tolerable, and were reported in only 2 patients on lorazepam.", "contents": "Antianxiety effects of lorazepam in patients with cardiovascular symptomatology. Lorazepam was administered to 38 patients with moderate to severe anxiety associated with cardiovascular symptomatology. A comparable group of patients on placebo (35) served as controls in this 4-week study. Average dosage was 3 mg/day given as 2 mg in the evening and 1 mg in the morning. The Global response, Hamilton Anxiety Rating Scale scores, and 35-Item Self-Rating Scale scores showed lorazepam to be significantly more effective in relieving anxiety than placebo, both clinically and statistically. Adverse reactions were transient and tolerable, and were reported in only 2 patients on lorazepam."}
{"id": "PMID:30767", "title": "The effect of lorazepam on hypertension-associated anxiety: a double-blind study.", "content": "Sixty-two adults with a current diagnosis of significant hypertension and accompanying moderate to severe anxiety were medicated with lorazepam or with placebo for a period of 4 weeks. The patients were assessed by 7 cardiologists under double-blind conditions and the results pooled. Symptoms of anxiety were quantified using a Global Physician Rating, the Hamilton Anxiety Scale and a Patient Self-Rating Scale. The symptoms of anxiety associated with hypertension were significantly relieved by lorazepam in comparison to placebo. Most lorazepam patients were controlled with 3 mg/day; except for 1 patient, side effects were mild and transient.", "contents": "The effect of lorazepam on hypertension-associated anxiety: a double-blind study. Sixty-two adults with a current diagnosis of significant hypertension and accompanying moderate to severe anxiety were medicated with lorazepam or with placebo for a period of 4 weeks. The patients were assessed by 7 cardiologists under double-blind conditions and the results pooled. Symptoms of anxiety were quantified using a Global Physician Rating, the Hamilton Anxiety Scale and a Patient Self-Rating Scale. The symptoms of anxiety associated with hypertension were significantly relieved by lorazepam in comparison to placebo. Most lorazepam patients were controlled with 3 mg/day; except for 1 patient, side effects were mild and transient."}
{"id": "PMID:30768", "title": "A clinical assessment of lorazepam in the treatment of anxiety associated with gastrointestinal symptomatology.", "content": "The effectiveness of lorazepam was assessed under double-blind conditions in 70 ambulant patients suffering from anxiety associated with gastrointestinal symptomatology. In this 4-week study, the usual daily dose of lorazepam, 3.0 mg given in a b.i.d. regimen, produced a greater decrease in symptoms associated with anxiety than placebo at almost all evaluation periods, as indicated by Kruskal-Wallis analyses of Global, Hamilton, and 35-Item ratings--a decrease which was clinically and statistically significant. In addition, lorazepam was well accepted and well tolerated by the majority of patients and was compatible with concomitant medications. Side effects were infrequent and usually controlled by dosage adjustment.", "contents": "A clinical assessment of lorazepam in the treatment of anxiety associated with gastrointestinal symptomatology. The effectiveness of lorazepam was assessed under double-blind conditions in 70 ambulant patients suffering from anxiety associated with gastrointestinal symptomatology. In this 4-week study, the usual daily dose of lorazepam, 3.0 mg given in a b.i.d. regimen, produced a greater decrease in symptoms associated with anxiety than placebo at almost all evaluation periods, as indicated by Kruskal-Wallis analyses of Global, Hamilton, and 35-Item ratings--a decrease which was clinically and statistically significant. In addition, lorazepam was well accepted and well tolerated by the majority of patients and was compatible with concomitant medications. Side effects were infrequent and usually controlled by dosage adjustment."}
{"id": "PMID:30769", "title": "Lorazepam in anxiety associated with chronic enteritis and ulcerative colitis.", "content": "Using a common protocol, 9 gastroenterologists assessed the comparative antianxiety efficacy of lorazepam and placebo under double-blind conditions in 48 patients with moderate to severe anxiety associated with chronic enteritis and ulcerative colitis. The initial dose of lorazepam was 3 mg per day given b.i.d., 2 mg h.s. and 1 mg a.m.; the duration of treatment was 4 weeks. The physician-rated Global and Hamilton and patient-rated 35-Item Scales were used. Efficacy was analyzed from the results of the pooled patient data. By all 3 rating scales and at virtually all times of assessment, lorazepam was associated with statistically significantly greater improvement in symptoms related to anxiety associated with chronic enteritis and ulcerative colitis than was placebo. Side effects in general were infrequent. (J Clin Psychiatry 39:[No. 10--2] 53--57, 1978).", "contents": "Lorazepam in anxiety associated with chronic enteritis and ulcerative colitis. Using a common protocol, 9 gastroenterologists assessed the comparative antianxiety efficacy of lorazepam and placebo under double-blind conditions in 48 patients with moderate to severe anxiety associated with chronic enteritis and ulcerative colitis. The initial dose of lorazepam was 3 mg per day given b.i.d., 2 mg h.s. and 1 mg a.m.; the duration of treatment was 4 weeks. The physician-rated Global and Hamilton and patient-rated 35-Item Scales were used. Efficacy was analyzed from the results of the pooled patient data. By all 3 rating scales and at virtually all times of assessment, lorazepam was associated with statistically significantly greater improvement in symptoms related to anxiety associated with chronic enteritis and ulcerative colitis than was placebo. Side effects in general were infrequent. (J Clin Psychiatry 39:[No. 10--2] 53--57, 1978)."}
{"id": "PMID:30771", "title": "Reversible conversion from Ca(2)+-ATPase activity to Mg(2)+- and Mn(2)+-ATPase activities of coupling factor purified from acetone powder of Rhodospirillum rubrum chromatophores.", "content": "It is known that the coupling factor purified from the acetone powder of chromatophores from Rhodospirillum rubrum shows ATPase activity in the presence of Ca(2)+, but not in the presence of Mg(2)+ or Mn(2)+. The present study deals with conditions, under which the Ca(2)+-ATPase activity is reversibly converted into Mg(2)+- and Mn(2)+-ATPase activites with the purified coupling factor. 1. Of the pH indicators tested, 6 kinds coverted the Ca(2)+-ATPase activity into Mg(2)+- and Mn(2)+-ATPase activities in the order, ethyl orange greater than tropaeolin 000 greater than or equal to metanil yellow greater than tropaeolin 00 greater than ethyl red greater than or equal to bromthymol blue. 2. Of the detergents tested, those other than Triton X-100 and Brij 58 caused the conversion described above; dodecylsulfonate was most effective, whereas dodecylpyridinium chloride was moderately effective. 3. 2,4-Dinitrophenol stimulated approximately two-fold the Ca(2)+-ATPase activity, but not the Mg(2)+- or Mn(2)+-ATPase activity at all. However, in the presence of dodecylpyridinium chloride, the pH indicator remarkably stimulated the Mg(2)+- and Mn(2)+-ATPase activities, accompanied with a partial inhibition of the Ca(2)+-ATPase activity. Methyl red and ethyl red showed similar effects. 4. All the nucleoside triphosphates tested can serve as the substrate. ATP was most effective for the Ca(2)+-ATPase activity, whereas dATP was most effective for the Mg(2)+- and Mn(2)+-ATPase activities induced by ethyl orange. 5. In the presence of ethyl orange, the ATPase activity was induced by various divalent cations in the following order of effectiveness, Mg(2)+ greater than Zn(2)+ greater than CO(2)+ greater than Mn(2)+ greater than Ni(2)+. 6. The mechanism of the reversible conversion from the Ca(2)+-ATPase activity to the Mg(2)+- and Mn(2)+-ATPase activities by pH indicators and detergents is discussed.", "contents": "Reversible conversion from Ca(2)+-ATPase activity to Mg(2)+- and Mn(2)+-ATPase activities of coupling factor purified from acetone powder of Rhodospirillum rubrum chromatophores. It is known that the coupling factor purified from the acetone powder of chromatophores from Rhodospirillum rubrum shows ATPase activity in the presence of Ca(2)+, but not in the presence of Mg(2)+ or Mn(2)+. The present study deals with conditions, under which the Ca(2)+-ATPase activity is reversibly converted into Mg(2)+- and Mn(2)+-ATPase activites with the purified coupling factor. 1. Of the pH indicators tested, 6 kinds coverted the Ca(2)+-ATPase activity into Mg(2)+- and Mn(2)+-ATPase activities in the order, ethyl orange greater than tropaeolin 000 greater than or equal to metanil yellow greater than tropaeolin 00 greater than ethyl red greater than or equal to bromthymol blue. 2. Of the detergents tested, those other than Triton X-100 and Brij 58 caused the conversion described above; dodecylsulfonate was most effective, whereas dodecylpyridinium chloride was moderately effective. 3. 2,4-Dinitrophenol stimulated approximately two-fold the Ca(2)+-ATPase activity, but not the Mg(2)+- or Mn(2)+-ATPase activity at all. However, in the presence of dodecylpyridinium chloride, the pH indicator remarkably stimulated the Mg(2)+- and Mn(2)+-ATPase activities, accompanied with a partial inhibition of the Ca(2)+-ATPase activity. Methyl red and ethyl red showed similar effects. 4. All the nucleoside triphosphates tested can serve as the substrate. ATP was most effective for the Ca(2)+-ATPase activity, whereas dATP was most effective for the Mg(2)+- and Mn(2)+-ATPase activities induced by ethyl orange. 5. In the presence of ethyl orange, the ATPase activity was induced by various divalent cations in the following order of effectiveness, Mg(2)+ greater than Zn(2)+ greater than CO(2)+ greater than Mn(2)+ greater than Ni(2)+. 6. The mechanism of the reversible conversion from the Ca(2)+-ATPase activity to the Mg(2)+- and Mn(2)+-ATPase activities by pH indicators and detergents is discussed."}
{"id": "PMID:30772", "title": "Nerve growth factor-mediated induction of tyrosine hydroxylase in rat superior cervical ganglia in vitro.", "content": "Exposure of rat sympathetic ganglia to 3 microgram/ml of 2.5 S nerve growth factor (NGF) resulted in a 100% increase in tyrosine hydroxylase activity within 48 h. Pulselabeling of proteins with [3H]leucine, followed by immunoprecipitation with antibodies to tyrosine hydorxylase and isolation of the precipitated enzyme by gel electrophoresis, demonstrated that the increase in tyrosine hydroxylase activity was due to enhanced de novo synthesis. The incorporation of [3H]leucine into tyrosine hydroxylase was increased by 150% compared to a 17% increase in total protein synthesis, which was not statistically significant. The fact that the half-life of pulse-labeled tyrosine hydroxylase was the same for NGF-treated and control organ cultures of superior cervical ganglia excludes the possibility that enhanced tyrosine hydroxylase labeling by NGF is due to decreased degradation. We conclude that, without modulatory factors which play a role in vivo, NGF can enhance the synthesis of tyrosine hydroxylase in sympathetic ganglia in vitro, provided organ culture conditions which permit optimal survival of adrenergic neurons are selected.", "contents": "Nerve growth factor-mediated induction of tyrosine hydroxylase in rat superior cervical ganglia in vitro. Exposure of rat sympathetic ganglia to 3 microgram/ml of 2.5 S nerve growth factor (NGF) resulted in a 100% increase in tyrosine hydroxylase activity within 48 h. Pulselabeling of proteins with [3H]leucine, followed by immunoprecipitation with antibodies to tyrosine hydorxylase and isolation of the precipitated enzyme by gel electrophoresis, demonstrated that the increase in tyrosine hydroxylase activity was due to enhanced de novo synthesis. The incorporation of [3H]leucine into tyrosine hydroxylase was increased by 150% compared to a 17% increase in total protein synthesis, which was not statistically significant. The fact that the half-life of pulse-labeled tyrosine hydroxylase was the same for NGF-treated and control organ cultures of superior cervical ganglia excludes the possibility that enhanced tyrosine hydroxylase labeling by NGF is due to decreased degradation. We conclude that, without modulatory factors which play a role in vivo, NGF can enhance the synthesis of tyrosine hydroxylase in sympathetic ganglia in vitro, provided organ culture conditions which permit optimal survival of adrenergic neurons are selected."}
{"id": "PMID:30773", "title": "Partial reactions of aminoacyl-tRNA synthetases as functions of pH.", "content": "The effect of pH on the properties of the partial reactions of arginyl-tRNA synthetase of E. coli has been investigated. V max of pyrophosphorolysis of arginyl adenylate has a pH optimum at pH 6.1, whereas V max of the transfer of arginine to tRNA has a pH optimum of 8.2. These values correlate with the pH optima of the ATP:PPi exchange and the overall esterification reaction, respectively. Only the pyrophosphorolysis reaction requires a divalent cation; transfer proceeds in the presence of EDTA. Inorganic pyrophosphate inhibits the transfer reaction to an extent independent of the concentration of tRNA; the maximum inhibition is a function of pH, corresponding to the relative rate of pyrophosphorolysis of the common intermediate compared with the rate of transfer. These results show that different groups on the enzyme participate in the rate-limiting steps of the two partial reactions and that these partial reactions have properties consistent with their participation in the overall esterification of arginine with tRNA.", "contents": "Partial reactions of aminoacyl-tRNA synthetases as functions of pH. The effect of pH on the properties of the partial reactions of arginyl-tRNA synthetase of E. coli has been investigated. V max of pyrophosphorolysis of arginyl adenylate has a pH optimum at pH 6.1, whereas V max of the transfer of arginine to tRNA has a pH optimum of 8.2. These values correlate with the pH optima of the ATP:PPi exchange and the overall esterification reaction, respectively. Only the pyrophosphorolysis reaction requires a divalent cation; transfer proceeds in the presence of EDTA. Inorganic pyrophosphate inhibits the transfer reaction to an extent independent of the concentration of tRNA; the maximum inhibition is a function of pH, corresponding to the relative rate of pyrophosphorolysis of the common intermediate compared with the rate of transfer. These results show that different groups on the enzyme participate in the rate-limiting steps of the two partial reactions and that these partial reactions have properties consistent with their participation in the overall esterification of arginine with tRNA."}
{"id": "PMID:30774", "title": "Regulation of rat liver acetyl-CoA carboxylase. Stimulation of phosphorylation and subsequent inactivation of liver acetyl-CoA carboxylase by cyclic 3':5'-monophosphate and effect on the structure of the enzyme.", "content": "The effects of citrate and cyclic AMP on the rate and degree of phosphorylation and inactivation of rat liver acetyl-CoA carboxylase were examined. High citrate concentrations (10 to 20 mM), which are generally used to stabilize and activate the enzyme, inhibit phosphorylation and inactivation of carboxylase. At lower concentrations of citrate, the rate and degree of phosphorylation are increased. Furthermore, phosphorylation and enzyme inactivation are affected by cyclic AMP under these conditions. At high citrate concentrations, cyclic AMP has little or no effect on inactivation and phosphorylation of acetyl-CoA carboxylase. Phosphorlation and inactivation of carboxylase is accompanied by depolymerization of the polymeric form of the enzyme into intermediate and protomeric forms. Depolymerization of carboxylase requires the transfer of the gamma-phosphate group from ATP to carboxylase. Inactivation occurs in the absence of CO2, which indicates that phosphorylation of the enzyme is the cause of inactivation and depolymerization, i.e. carboxylation of the enzyme is not responsible for inactivation of the enzyme.", "contents": "Regulation of rat liver acetyl-CoA carboxylase. Stimulation of phosphorylation and subsequent inactivation of liver acetyl-CoA carboxylase by cyclic 3':5'-monophosphate and effect on the structure of the enzyme. The effects of citrate and cyclic AMP on the rate and degree of phosphorylation and inactivation of rat liver acetyl-CoA carboxylase were examined. High citrate concentrations (10 to 20 mM), which are generally used to stabilize and activate the enzyme, inhibit phosphorylation and inactivation of carboxylase. At lower concentrations of citrate, the rate and degree of phosphorylation are increased. Furthermore, phosphorylation and enzyme inactivation are affected by cyclic AMP under these conditions. At high citrate concentrations, cyclic AMP has little or no effect on inactivation and phosphorylation of acetyl-CoA carboxylase. Phosphorlation and inactivation of carboxylase is accompanied by depolymerization of the polymeric form of the enzyme into intermediate and protomeric forms. Depolymerization of carboxylase requires the transfer of the gamma-phosphate group from ATP to carboxylase. Inactivation occurs in the absence of CO2, which indicates that phosphorylation of the enzyme is the cause of inactivation and depolymerization, i.e. carboxylation of the enzyme is not responsible for inactivation of the enzyme."}
{"id": "PMID:30775", "title": "Effect of epinephrine on acetyl-CoA carboxylase in rat epididymal fat tissue.", "content": "If acetyl-CoA carboxylase in epididymal fat tissue is subject to control by convalent modification as in the case of the liver enzyme, catalytically different forms of carboxylase should exist, independent of polymerization. By treating epididymal fat tissue in culture with epinephrine, we have demonstrated catalytically less active forms of acetyl-CoA carboxylase. The catalytically less active forms of the enzyme reacted to antibody with the same efficiency as the active form of carboxylase. However, the less active enzyme formed by epinephrine treatment of tissues has a sedimentation constant of 30 to 35 S, whereas that of the enzyme from control tissue is 45 S. Incubation of the less active forms of the carboxylase with 10 mM citrate and up to 10 mg/ml of bovine serum albumin activated the enzyme without any change in the sedimentation constant. Therefore, the less active forms of the carboxylase formed as a result of epinephrine treatment are not due to the depolymerization of polymeric forms (45 S) to the protomeric forms (17 to 20 S), but to the formation of intermediate species of carboxylase which cannot form polymeric enzyme (45 S) in the presence of high concentrations of citrate.", "contents": "Effect of epinephrine on acetyl-CoA carboxylase in rat epididymal fat tissue. If acetyl-CoA carboxylase in epididymal fat tissue is subject to control by convalent modification as in the case of the liver enzyme, catalytically different forms of carboxylase should exist, independent of polymerization. By treating epididymal fat tissue in culture with epinephrine, we have demonstrated catalytically less active forms of acetyl-CoA carboxylase. The catalytically less active forms of the enzyme reacted to antibody with the same efficiency as the active form of carboxylase. However, the less active enzyme formed by epinephrine treatment of tissues has a sedimentation constant of 30 to 35 S, whereas that of the enzyme from control tissue is 45 S. Incubation of the less active forms of the carboxylase with 10 mM citrate and up to 10 mg/ml of bovine serum albumin activated the enzyme without any change in the sedimentation constant. Therefore, the less active forms of the carboxylase formed as a result of epinephrine treatment are not due to the depolymerization of polymeric forms (45 S) to the protomeric forms (17 to 20 S), but to the formation of intermediate species of carboxylase which cannot form polymeric enzyme (45 S) in the presence of high concentrations of citrate."}
{"id": "PMID:30777", "title": "The unfolding of the cytochromes c in methanol and acid.", "content": "The cytochromes c are a family of hemoproteins that share a number of structural features: a thioether linkage between the protein and the heme, histidine and methionine as the fifth and sixth iron ligands, and a tertiary structure known as the \"cytochrome fold.\" These proteins follow a common mechanism of equilibrium unfolding in methanol and acid, differing only in their reactivity to the denaturing conditions. The reduced cytochromes c exhibit an increased conformational stability which is consistent with the presence of a strengthened iron-methionine linkage in the reduced state.", "contents": "The unfolding of the cytochromes c in methanol and acid. The cytochromes c are a family of hemoproteins that share a number of structural features: a thioether linkage between the protein and the heme, histidine and methionine as the fifth and sixth iron ligands, and a tertiary structure known as the \"cytochrome fold.\" These proteins follow a common mechanism of equilibrium unfolding in methanol and acid, differing only in their reactivity to the denaturing conditions. The reduced cytochromes c exhibit an increased conformational stability which is consistent with the presence of a strengthened iron-methionine linkage in the reduced state."}
{"id": "PMID:30778", "title": "Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation.", "content": "Purification of soluble guanylate cyclase activity from rat liver resulted in loss of enzyme responsiveness to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), nitroprusside, nitrite, and NO. Responses were restored by addition of heat-treated hepatic supernatant fraction, implying a requirement for heat-stable soluble factor(s) in the optimal expression of the actions of the activators. Addition of free hematin, hemoglobin, methemoglobin, active or heat-inactivated catalase partially restores responsiveness of purified guanylate cyclase to MNNG, NO, nitrite, and nitroprusside. These responses were markedly potentiated by the presence of an appropriate concentration of reducing agent (dithiothreitol, ascorbate, cysteine, or glutathione), which maintains heme iron in the ferro form and favors formation of paramagnetic nitrosyl . heme complexes from the activators. High concentrations of heme or reducing agents were inhibitory, and heme was not required for the expression of the stimulatory effects of Mn2+ or Mg2+ on purified guanylate cyclase. Preformed nitrosyl hemoglobin (10 micron) increased activity of the purified enzyme 10- to 20-fold over basal with Mn2+ as the metal cofactor and 90- to 100-fold with Mg2+. Purified guanylate cyclase was more sensitive to preformed NO-hemoglobin (minimally effective concentration, 0.1 micron) than to MNNG (1 micron), nitroprusside (50 micron), or nitrite (1 mM). A reducing agent was not required for optimal stimulation of guanylate cyclase by NO-hemoglobin. Maximal NO-hemoglobin-responsive guanylate cyclase was not further increased by subsequent addition of NO, MNNG, nitrite, or nitroprusside. Activation by each agent resulted in analogous alterations in the Mn2+ and Mg2+ requirements of enzyme activity, and responses were inhibited by the thiol-blocking agents N-ethylmaleimide, arsenite, or iodoacetamide. The results suggest that NO-hemoglobin, MNNG, NO, nitrite, and nitroprusside activate guanylate cyclase through similar mechanisms. The stimulatory effects of preformed NO-hemoglobin combined with the clear requirements for heme plus a reducing agent in the optimal expression of the actions of MNNG, NO, and related agents are consistent with a role for the paramagnetic nitrosyl . heme complex in the activation of guanylate cyclase.", "contents": "Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. Purification of soluble guanylate cyclase activity from rat liver resulted in loss of enzyme responsiveness to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), nitroprusside, nitrite, and NO. Responses were restored by addition of heat-treated hepatic supernatant fraction, implying a requirement for heat-stable soluble factor(s) in the optimal expression of the actions of the activators. Addition of free hematin, hemoglobin, methemoglobin, active or heat-inactivated catalase partially restores responsiveness of purified guanylate cyclase to MNNG, NO, nitrite, and nitroprusside. These responses were markedly potentiated by the presence of an appropriate concentration of reducing agent (dithiothreitol, ascorbate, cysteine, or glutathione), which maintains heme iron in the ferro form and favors formation of paramagnetic nitrosyl . heme complexes from the activators. High concentrations of heme or reducing agents were inhibitory, and heme was not required for the expression of the stimulatory effects of Mn2+ or Mg2+ on purified guanylate cyclase. Preformed nitrosyl hemoglobin (10 micron) increased activity of the purified enzyme 10- to 20-fold over basal with Mn2+ as the metal cofactor and 90- to 100-fold with Mg2+. Purified guanylate cyclase was more sensitive to preformed NO-hemoglobin (minimally effective concentration, 0.1 micron) than to MNNG (1 micron), nitroprusside (50 micron), or nitrite (1 mM). A reducing agent was not required for optimal stimulation of guanylate cyclase by NO-hemoglobin. Maximal NO-hemoglobin-responsive guanylate cyclase was not further increased by subsequent addition of NO, MNNG, nitrite, or nitroprusside. Activation by each agent resulted in analogous alterations in the Mn2+ and Mg2+ requirements of enzyme activity, and responses were inhibited by the thiol-blocking agents N-ethylmaleimide, arsenite, or iodoacetamide. The results suggest that NO-hemoglobin, MNNG, NO, nitrite, and nitroprusside activate guanylate cyclase through similar mechanisms. The stimulatory effects of preformed NO-hemoglobin combined with the clear requirements for heme plus a reducing agent in the optimal expression of the actions of MNNG, NO, and related agents are consistent with a role for the paramagnetic nitrosyl . heme complex in the activation of guanylate cyclase."}
{"id": "PMID:30780", "title": "The sensitivity of hemoglobin oxygen affinity to diphosphoglycerate and the characteristic pH of methemoglobin.", "content": "The sensitivity of the oxygen affinity of a hemoglobin to 2,3-diphosphoglyceric acid concentration has been defined as the change in log1/2O2 (deltalogp1/2O2) which results from saturating the hemoglobin with 2,3-diphosphoglyceric acid. The sensitivity varies from one hemoglobin species to another and is linearly rated to the difference in the logarithm of the binding constants of 2,3-diphosphoglyceric acid to deoxy- and oxyhemoglobin, the characteristic pH (pHch), and inversely proportional to the magnitude of the alkaline Bohr effect measured in a saturating amount of 2,3-diphosphoglyceric acid. Its magnitude is higher in large animals than in small animals and varies linearly with the charged amino acid composition of the hemoglobin. The charged amino acid residues must have been selected for in mammals with high metabolic needs and against in animals with low metabolic needs. Variability in the effect of 2,3-diphosphoglyceric acid on the oxygen transport in the different animal hemoglobins must therefore be the result of a positive Darwinian Selection of the charged amino acid residues in their hemoglobins. Furthermore, all the charged groups and not those at the binding site alone, affect the 2,3-diphosphoglyceric acid binding constant of a hemoglobin.", "contents": "The sensitivity of hemoglobin oxygen affinity to diphosphoglycerate and the characteristic pH of methemoglobin. The sensitivity of the oxygen affinity of a hemoglobin to 2,3-diphosphoglyceric acid concentration has been defined as the change in log1/2O2 (deltalogp1/2O2) which results from saturating the hemoglobin with 2,3-diphosphoglyceric acid. The sensitivity varies from one hemoglobin species to another and is linearly rated to the difference in the logarithm of the binding constants of 2,3-diphosphoglyceric acid to deoxy- and oxyhemoglobin, the characteristic pH (pHch), and inversely proportional to the magnitude of the alkaline Bohr effect measured in a saturating amount of 2,3-diphosphoglyceric acid. Its magnitude is higher in large animals than in small animals and varies linearly with the charged amino acid composition of the hemoglobin. The charged amino acid residues must have been selected for in mammals with high metabolic needs and against in animals with low metabolic needs. Variability in the effect of 2,3-diphosphoglyceric acid on the oxygen transport in the different animal hemoglobins must therefore be the result of a positive Darwinian Selection of the charged amino acid residues in their hemoglobins. Furthermore, all the charged groups and not those at the binding site alone, affect the 2,3-diphosphoglyceric acid binding constant of a hemoglobin."}
{"id": "PMID:30782", "title": "Platelet derived growth factor(s) for a hormone-responsive rat mammary tumor cell line.", "content": "Mammary tumor cell growth factor(s) has been identified in extracts of platelets from both male and female rats, as well as in extracts prepared from pooled outdated human platelets. When assayed by the growth promotion of MTW9/PL rat mammary tumor cells in culture, platelet extracts alone were able to support growth 50--75% as well as whole serum. The mitogenic activity from crude human platelet lysates was shown to be trypsin sensitive, relatively stable to extremes of pH, labile to heat treatment at 70 degrees, non-dialysable, ammonium sulfate precipitable, not removed by 56 degrees charcoal treatment, and of apparent molecular weight of 30,000 to 50,000 daltons as estimated by G-100 Sephadex chromatography. The platelet derived mammary growth factor activity was not replaced or potentiated by thrombin or known hormones and growth factors such as prolactin, insulin, 17-beta-estradiol, progesterone, hydrocortisone, L-thyroxine, and mouse epidermal growth factor. The experimental report demonstrates that platelets are a rich source growth factor activity for rat epithelial mammary tumor cells, and that the activity appears to be a polypeptide(s) different from other mitogenic activities known to influence growth of mammary tissue.", "contents": "Platelet derived growth factor(s) for a hormone-responsive rat mammary tumor cell line. Mammary tumor cell growth factor(s) has been identified in extracts of platelets from both male and female rats, as well as in extracts prepared from pooled outdated human platelets. When assayed by the growth promotion of MTW9/PL rat mammary tumor cells in culture, platelet extracts alone were able to support growth 50--75% as well as whole serum. The mitogenic activity from crude human platelet lysates was shown to be trypsin sensitive, relatively stable to extremes of pH, labile to heat treatment at 70 degrees, non-dialysable, ammonium sulfate precipitable, not removed by 56 degrees charcoal treatment, and of apparent molecular weight of 30,000 to 50,000 daltons as estimated by G-100 Sephadex chromatography. The platelet derived mammary growth factor activity was not replaced or potentiated by thrombin or known hormones and growth factors such as prolactin, insulin, 17-beta-estradiol, progesterone, hydrocortisone, L-thyroxine, and mouse epidermal growth factor. The experimental report demonstrates that platelets are a rich source growth factor activity for rat epithelial mammary tumor cells, and that the activity appears to be a polypeptide(s) different from other mitogenic activities known to influence growth of mammary tissue."}
{"id": "PMID:30784", "title": "The relationship between guilt and quality of drug experiences.", "content": "Consistent with predictions from Mosher's (1966) guilt construct, the present study found that high guilt males, compared with low guilt Ss, reported significantly less use of marijuana, depressant, stimulant and hallucinogenic drugs. Among all Ss who reported at least one use within each drug category, high guilt Ss rated their experiences as less pleasant and reported a higher frequency of \"bad trips\" than did low guilt individuals. Overall, these results support Mosher's contention that high vs. low guilt Ss are less likely to engage in culturally prohibited activities such as drug use and are more likely to have unpleasant experiences resulting from guilt when such activities are pursued.", "contents": "The relationship between guilt and quality of drug experiences. Consistent with predictions from Mosher's (1966) guilt construct, the present study found that high guilt males, compared with low guilt Ss, reported significantly less use of marijuana, depressant, stimulant and hallucinogenic drugs. Among all Ss who reported at least one use within each drug category, high guilt Ss rated their experiences as less pleasant and reported a higher frequency of \"bad trips\" than did low guilt individuals. Overall, these results support Mosher's contention that high vs. low guilt Ss are less likely to engage in culturally prohibited activities such as drug use and are more likely to have unpleasant experiences resulting from guilt when such activities are pursued."}
{"id": "PMID:30783", "title": "Cobalamin binding and cobalamin-dependent enzyme activity in normal and mutant human fibroblasts.", "content": "We have studied the intracellular binding of radioactive cobalamin by normal cultured human fibroblasts grown in medium containing [(57)Co]-cobalamin. We have also assessed the significance of defects in this binding activity exhibited by two classes of human mutants (cbl C and cbl D) each characterized by pleiotropic deficiencies in the accumulation and retention of cobalamin, in the synthesis of cobalamin coenzymes, and accordingly, in the holoenzyme activities of both cobalamin-dependent enzymes, 5-methyltetrahydrofolate:homocysteine methyltransferase and methylmalonyl-CoA mutase. Based on the coincidence of [(57)Co]cobalamin binding and cobalamin-dependent enzyme activities after Sephadex G-150 chromatography and polyacrylamide gel electrophoresis, we conclude that, as in rat liver, the intracellular binding of labeled cobalamin by normal fibroblasts reflects the attachment of the vitamin to the cobalamin-dependent methyltransferase and mutase. Whereas cbl C cells are completely deficient in the binding of [(57)Co]cobalamin to either enzyme, fibroblasts which bear the phenotypically similar but genetically distinct cbl D mutation retain some binding activity, and accordingly, have higher holomethyltransferase and holomutase activities than do cbl C cells. The defect in [(57)Co]-cobalamin binding exhibited by both cbl C and cbl D fibroblasts is almost certainly not a result of mutations which affect the methyltransferase or mutase apoenzymes, since the electrophoretic mobilities and the affinities of these enzymes for their respective cobalamin coenzymes are indistinguishable from those in control cell extracts. These results suggest that both the cbl C and cbl D mutations affect some enzymatic step(s) which converts newly taken up cobalamin to a form capable of being bound by the two cobalamin-dependent enzymes.", "contents": "Cobalamin binding and cobalamin-dependent enzyme activity in normal and mutant human fibroblasts. We have studied the intracellular binding of radioactive cobalamin by normal cultured human fibroblasts grown in medium containing [(57)Co]-cobalamin. We have also assessed the significance of defects in this binding activity exhibited by two classes of human mutants (cbl C and cbl D) each characterized by pleiotropic deficiencies in the accumulation and retention of cobalamin, in the synthesis of cobalamin coenzymes, and accordingly, in the holoenzyme activities of both cobalamin-dependent enzymes, 5-methyltetrahydrofolate:homocysteine methyltransferase and methylmalonyl-CoA mutase. Based on the coincidence of [(57)Co]cobalamin binding and cobalamin-dependent enzyme activities after Sephadex G-150 chromatography and polyacrylamide gel electrophoresis, we conclude that, as in rat liver, the intracellular binding of labeled cobalamin by normal fibroblasts reflects the attachment of the vitamin to the cobalamin-dependent methyltransferase and mutase. Whereas cbl C cells are completely deficient in the binding of [(57)Co]cobalamin to either enzyme, fibroblasts which bear the phenotypically similar but genetically distinct cbl D mutation retain some binding activity, and accordingly, have higher holomethyltransferase and holomutase activities than do cbl C cells. The defect in [(57)Co]-cobalamin binding exhibited by both cbl C and cbl D fibroblasts is almost certainly not a result of mutations which affect the methyltransferase or mutase apoenzymes, since the electrophoretic mobilities and the affinities of these enzymes for their respective cobalamin coenzymes are indistinguishable from those in control cell extracts. These results suggest that both the cbl C and cbl D mutations affect some enzymatic step(s) which converts newly taken up cobalamin to a form capable of being bound by the two cobalamin-dependent enzymes."}
{"id": "PMID:30781", "title": "A new anticoagulant medication in cardiac valve replacement.", "content": "1. In the mitral valve replacement with Starr-Edwards prosthetic ball valve, the major thromboembolism occurred in 20% of the patients with the silastic ball valve series compared with 6% in those with a metal ball valve series. 2. The anticoagulant effect of Warfarin became stable and the occurrence of thromboembolism was reduced by the addition of Bucolome.", "contents": "A new anticoagulant medication in cardiac valve replacement. 1. In the mitral valve replacement with Starr-Edwards prosthetic ball valve, the major thromboembolism occurred in 20% of the patients with the silastic ball valve series compared with 6% in those with a metal ball valve series. 2. The anticoagulant effect of Warfarin became stable and the occurrence of thromboembolism was reduced by the addition of Bucolome."}
{"id": "PMID:30787", "title": "The influence of fluoride on apatite formation from unstable supersaturated solutions at pH 7.4.", "content": "The present study was undertaken to examine the effect of fluoride on the formation of apatite in aqeous calcium phosphate suspensions prepared by spontaneous precipitation at pH 7.4. The most notable finding was that fluoride greatly curtailed or eliminated the appearance of octacalcium phosphate-like precursor phases in these preparations.", "contents": "The influence of fluoride on apatite formation from unstable supersaturated solutions at pH 7.4. The present study was undertaken to examine the effect of fluoride on the formation of apatite in aqeous calcium phosphate suspensions prepared by spontaneous precipitation at pH 7.4. The most notable finding was that fluoride greatly curtailed or eliminated the appearance of octacalcium phosphate-like precursor phases in these preparations."}
{"id": "PMID:30799", "title": "Acid lipase: a histochemical and biochemical study using triton X100-naphtyl palmitate micelles.", "content": "Hydrolsis of a-naphtyl palmitate dispersed with the detergent Triton X-100 at acid pH was studied by a histochemical diazocoupling technique in both fixed sections and cultures of primate tissues as well as by a biochemical assay employing the same chromogenic substrate. Evidence for the exclusive hydrolysis of this artificial fatty acid ester substrate by acid lipases was gathered from (1) comparison of isoelectric focusing zymograms developed with different substrates, (2) kinetic analysis of enzyme activity in the presence or absence of inhibitors, including a natural substrate of acid lipase, trioleylglycerol, (3) specific localization of marked enzyme activity in certain tissues, and (4) absence of detectable enzyme activity in a case of human acid lipase deficiency (Wolman's disease). Histochemically, acid lipase activity was most readily detected in cells active in the uptake and processing of neutral lipids, i.e., the phagocytes of the reticuloendothelial system, the adrenal cortex and the lipid-storing cells in the athero-sclerotic plaques of arteries.", "contents": "Acid lipase: a histochemical and biochemical study using triton X100-naphtyl palmitate micelles. Hydrolsis of a-naphtyl palmitate dispersed with the detergent Triton X-100 at acid pH was studied by a histochemical diazocoupling technique in both fixed sections and cultures of primate tissues as well as by a biochemical assay employing the same chromogenic substrate. Evidence for the exclusive hydrolysis of this artificial fatty acid ester substrate by acid lipases was gathered from (1) comparison of isoelectric focusing zymograms developed with different substrates, (2) kinetic analysis of enzyme activity in the presence or absence of inhibitors, including a natural substrate of acid lipase, trioleylglycerol, (3) specific localization of marked enzyme activity in certain tissues, and (4) absence of detectable enzyme activity in a case of human acid lipase deficiency (Wolman's disease). Histochemically, acid lipase activity was most readily detected in cells active in the uptake and processing of neutral lipids, i.e., the phagocytes of the reticuloendothelial system, the adrenal cortex and the lipid-storing cells in the athero-sclerotic plaques of arteries."}
{"id": "PMID:30800", "title": "On testing the activity of proteases from human polymorphonuclear neutrophils on blood smears.", "content": "A cytochemical method is presented for the demonstration of proteases in human polymorphonuclear (PMN) neutrophils on fixed blood smears. This new technique is based on solubilization of proteases from PMN neutrophils by incubation with 0.25 M NaCl in borate buffer at pH 8.5 which leads to degradation of erythrocytes and plasma in a disclike zone (halo) around centrally situated PMN neutrophils, an effect that is visualized by staining smears using a modified colloidal iron reaction. Halo formation is inhibited by trypsin inhibitors of soya-bean as well as of chicken egg white mucoid and by phenylmethyl-sulfonylfluoride.", "contents": "On testing the activity of proteases from human polymorphonuclear neutrophils on blood smears. A cytochemical method is presented for the demonstration of proteases in human polymorphonuclear (PMN) neutrophils on fixed blood smears. This new technique is based on solubilization of proteases from PMN neutrophils by incubation with 0.25 M NaCl in borate buffer at pH 8.5 which leads to degradation of erythrocytes and plasma in a disclike zone (halo) around centrally situated PMN neutrophils, an effect that is visualized by staining smears using a modified colloidal iron reaction. Halo formation is inhibited by trypsin inhibitors of soya-bean as well as of chicken egg white mucoid and by phenylmethyl-sulfonylfluoride."}
{"id": "PMID:30802", "title": "The beta-adrenergic receptor of newborn mouse skin.", "content": "Binding of the potent beta-adrenergic antagonist [125I]iodohydroxybenzylpindolol ([125I]IHYP) to particulate preparations from newborn mouse skin was characterized. A number of criteria were used to establish that binding occurred to specific, high affinity beta-adrenergic receptors in the skin preparations. Thus specific binding (that displaced by 10 micrometer concentrations of the beta-adrenergic antagonist (-)propranolol) reached equilibrium in 15--20 min, was saturable (ligand concentration for half-maximal saturation, 0.25 nM) and freely reversible. Stereoselectivity of binding was demonstrated by the observation that displacement of [125I]IHYP by (-)propranolol occurred at concentrations at least 100 times lower than with (+)isoproterenol. Displacement was also observed with the beta-adrenergic agonists (-)isoproterenol, (-)epinephrine and (-)norepinephrine, but not with the alpha-adrenergic antagonist phentolamine.", "contents": "The beta-adrenergic receptor of newborn mouse skin. Binding of the potent beta-adrenergic antagonist [125I]iodohydroxybenzylpindolol ([125I]IHYP) to particulate preparations from newborn mouse skin was characterized. A number of criteria were used to establish that binding occurred to specific, high affinity beta-adrenergic receptors in the skin preparations. Thus specific binding (that displaced by 10 micrometer concentrations of the beta-adrenergic antagonist (-)propranolol) reached equilibrium in 15--20 min, was saturable (ligand concentration for half-maximal saturation, 0.25 nM) and freely reversible. Stereoselectivity of binding was demonstrated by the observation that displacement of [125I]IHYP by (-)propranolol occurred at concentrations at least 100 times lower than with (+)isoproterenol. Displacement was also observed with the beta-adrenergic agonists (-)isoproterenol, (-)epinephrine and (-)norepinephrine, but not with the alpha-adrenergic antagonist phentolamine."}
{"id": "PMID:30803", "title": "Modification of otitis media following vaccination with the capsular polysaccharide of Streptococcus pneumoniae in chinchillas.", "content": "An animal model was used to determine whether vaccination with the capsular polysaccharide of Streptococcus pneumoniae could alter the development of experimental otitis media induced by the same type of S. pneumoniae as the vaccine. Following vaccination with the capsular polysaccharide of S. pneumoniae type 7, 36(63%) of 57 chinchillas seroconverted with at least a 100% increase in concentration of antibody in serum which remained elevated for at least six weeks. The middle ears of 23 chinchillas that were vaccinated and seroconverted, 13 that were vaccinated and did not seroconvert, and 47 that were not vaccinated were inoculated with S. pneumoniae type 7. Vaccinated animals that seroconverted developed otitis media as readily as nonseroconverting and unvaccinated animals but had fewer pneumococci in their middle ears, a lower incidence of bacteremia, and lower mortality rates during the first week after inoculation of bacteria. Animals that did not seroconvert showed no evidence of modification of their middle ear infections. These results indicate that type 7 pneumococcal capsular polysaccharide vaccine is antigenic for the chinchilla and modifies experimental otitis media due to type 7 S. pneumoniae.", "contents": "Modification of otitis media following vaccination with the capsular polysaccharide of Streptococcus pneumoniae in chinchillas. An animal model was used to determine whether vaccination with the capsular polysaccharide of Streptococcus pneumoniae could alter the development of experimental otitis media induced by the same type of S. pneumoniae as the vaccine. Following vaccination with the capsular polysaccharide of S. pneumoniae type 7, 36(63%) of 57 chinchillas seroconverted with at least a 100% increase in concentration of antibody in serum which remained elevated for at least six weeks. The middle ears of 23 chinchillas that were vaccinated and seroconverted, 13 that were vaccinated and did not seroconvert, and 47 that were not vaccinated were inoculated with S. pneumoniae type 7. Vaccinated animals that seroconverted developed otitis media as readily as nonseroconverting and unvaccinated animals but had fewer pneumococci in their middle ears, a lower incidence of bacteremia, and lower mortality rates during the first week after inoculation of bacteria. Animals that did not seroconvert showed no evidence of modification of their middle ear infections. These results indicate that type 7 pneumococcal capsular polysaccharide vaccine is antigenic for the chinchilla and modifies experimental otitis media due to type 7 S. pneumoniae."}
{"id": "PMID:30804", "title": "Correction of metabolic acidosis by the kidney during isometric expansion of extracellular fluid volume.", "content": "In dogs with chronic hypochloremic metabolic alkalosis associated with ECFV contraction, plasma [HCO-3] ([HCO-3]p) normalizes during expansion of ECFV with a solution containing Cl- and HCO-3 in concentrations duplicating those in the plasma before expansion (isometric expansion). The kidney selectively rejects administered HCO-3 and retains Cl-. If this preferential Cl- less than HCO-3 reabsorptive selectivity were a characteristic renal response to ECFV expansion, isometric expansion during hyperchloremic acidosis would exacerbate the acid-base disturbance rather than correct it as it does in alkalosis. We examined the effect of isometric expansion in dogs with chronic hyperchloremic metabolic acidosis induced by HCl feeding or mineralocorticoid hormone deficiency. During expansion, as the expected decrease occurred in the fractional reabsorption of Na+, a lesser decrease occurred in fractional reabsorption of HCO-3, whereas a greater decrease occurred in fractional reabsorption of Cl-. The kidney selectively retained administered HCO3 and rejected Cl-. [HCO-3]p normalized. The shift to bicarbonate-selective from chloride-selective anion reabsorption during ECFV expansion in metabolic acidosis vs. metabolic alkalosis indicates that in response to ECFV expansion- the kidney selectively alters the ratio of bicarbonate to chloride concentration in the tubular reabsorbate in the direction that tends to normalize plasma acid-base composition, irrespective of the direction of deviation of the initial plasma bicarbonate concentration. The signal that initiates the shift in anion reabsorptive selectivity remains to be identified.", "contents": "Correction of metabolic acidosis by the kidney during isometric expansion of extracellular fluid volume. In dogs with chronic hypochloremic metabolic alkalosis associated with ECFV contraction, plasma [HCO-3] ([HCO-3]p) normalizes during expansion of ECFV with a solution containing Cl- and HCO-3 in concentrations duplicating those in the plasma before expansion (isometric expansion). The kidney selectively rejects administered HCO-3 and retains Cl-. If this preferential Cl- less than HCO-3 reabsorptive selectivity were a characteristic renal response to ECFV expansion, isometric expansion during hyperchloremic acidosis would exacerbate the acid-base disturbance rather than correct it as it does in alkalosis. We examined the effect of isometric expansion in dogs with chronic hyperchloremic metabolic acidosis induced by HCl feeding or mineralocorticoid hormone deficiency. During expansion, as the expected decrease occurred in the fractional reabsorption of Na+, a lesser decrease occurred in fractional reabsorption of HCO-3, whereas a greater decrease occurred in fractional reabsorption of Cl-. The kidney selectively retained administered HCO3 and rejected Cl-. [HCO-3]p normalized. The shift to bicarbonate-selective from chloride-selective anion reabsorption during ECFV expansion in metabolic acidosis vs. metabolic alkalosis indicates that in response to ECFV expansion- the kidney selectively alters the ratio of bicarbonate to chloride concentration in the tubular reabsorbate in the direction that tends to normalize plasma acid-base composition, irrespective of the direction of deviation of the initial plasma bicarbonate concentration. The signal that initiates the shift in anion reabsorptive selectivity remains to be identified."}
{"id": "PMID:30806", "title": "Analysis of the iron-binding sites of transferrin by isoelectric focussing.", "content": "1. Human transferrin was labelled with ferric nitrilotriacetate (FeNTA) at one of its two metal binding sites by variation of the pH. 2. Four transferrin forms, transferrin, transferrin(Fe) (A-site), transferrin(Fe) (B-site) and transferrin(2Fe) could be separated on flat bed gels by isoelectric focussing. 3. Incubation time, temperature and medium play an important role in the specificity of the binding of Fe. In NTA-pH-buffer, at 0.5 Fe-saturation, the A-site was preferentially labelled at pH 7--8, the B-site at a pH 8--9. 4. Under physiological conditions iron from the B-site has the tendency to move to the A-site.", "contents": "Analysis of the iron-binding sites of transferrin by isoelectric focussing. 1. Human transferrin was labelled with ferric nitrilotriacetate (FeNTA) at one of its two metal binding sites by variation of the pH. 2. Four transferrin forms, transferrin, transferrin(Fe) (A-site), transferrin(Fe) (B-site) and transferrin(2Fe) could be separated on flat bed gels by isoelectric focussing. 3. Incubation time, temperature and medium play an important role in the specificity of the binding of Fe. In NTA-pH-buffer, at 0.5 Fe-saturation, the A-site was preferentially labelled at pH 7--8, the B-site at a pH 8--9. 4. Under physiological conditions iron from the B-site has the tendency to move to the A-site."}
{"id": "PMID:30807", "title": "[Induction of tyrosine aminotransferase (EC 2.5.1.5) by nicotinamide in rat liver (author's transl)].", "content": "In intact rats nicotinamide induces an increase of tyrosine aminotransferase depending on the dose of nicotinamide. In adrenalectomized rats an increase of tyrosine aminotransferase activity is only found up to a dose of 250 mg/kg nicotinamide. The combination of nicotinamide with L-methionine and/or cortisone acetate does not cause a significant increase of the enzyme activity, which, however, can be seen in the presence of L-tyrosine.", "contents": "[Induction of tyrosine aminotransferase (EC 2.5.1.5) by nicotinamide in rat liver (author's transl)]. In intact rats nicotinamide induces an increase of tyrosine aminotransferase depending on the dose of nicotinamide. In adrenalectomized rats an increase of tyrosine aminotransferase activity is only found up to a dose of 250 mg/kg nicotinamide. The combination of nicotinamide with L-methionine and/or cortisone acetate does not cause a significant increase of the enzyme activity, which, however, can be seen in the presence of L-tyrosine."}
{"id": "PMID:30809", "title": "Microbiology of recurrent and chronic otitis media with effusion.", "content": "A study was conducted of 274 children who had recurrent acute or chronic otitis media with effusion. Forty-five percent of the ears with effusion were found to contain bacteria, and 11% contained bacteria that were \"probable pathogens\" (S. pneumoniae, H. influenzae, and S. pyogenes). Bacteria were also found in 40% of the ears without effusions. The type of organism found did not vary with the age of the patient studied or the season of the year. The significance of these bacteria in the etiology of recurrent acute or chronic otitis media with effusion remains to be demonstrated.", "contents": "Microbiology of recurrent and chronic otitis media with effusion. A study was conducted of 274 children who had recurrent acute or chronic otitis media with effusion. Forty-five percent of the ears with effusion were found to contain bacteria, and 11% contained bacteria that were \"probable pathogens\" (S. pneumoniae, H. influenzae, and S. pyogenes). Bacteria were also found in 40% of the ears without effusions. The type of organism found did not vary with the age of the patient studied or the season of the year. The significance of these bacteria in the etiology of recurrent acute or chronic otitis media with effusion remains to be demonstrated."}
{"id": "PMID:30810", "title": "Angiography of the testicular artery as a diagnostic aid in boys with nonpalpable testis.", "content": "Selective angiography of the testicular artery was performed in 12 boys (age 3-14 yr) with nonpalpable testis. The angiographic, operative, and microscopic findings are described. True aplasia was diagnosed in seven patients. In three patients previously operated upon, the second exploration was facilitated by angiography. This method might be a valuable diagnostic aid in selected cases previously operated for gonadal disorders or inadequately explored for cryptorchism in order to avoid more extensive surgical exploration.", "contents": "Angiography of the testicular artery as a diagnostic aid in boys with nonpalpable testis. Selective angiography of the testicular artery was performed in 12 boys (age 3-14 yr) with nonpalpable testis. The angiographic, operative, and microscopic findings are described. True aplasia was diagnosed in seven patients. In three patients previously operated upon, the second exploration was facilitated by angiography. This method might be a valuable diagnostic aid in selected cases previously operated for gonadal disorders or inadequately explored for cryptorchism in order to avoid more extensive surgical exploration."}
{"id": "PMID:30812", "title": "Time-dependent deformation of some direct compression excipients.", "content": "Three techniques were used to compare the time-dependent deformation of microfine cellulose (Elcema G250), anhydrous lactose, dicalcium phosphate dihydrate (Emcompress), modified starch (Sta-Rx 1500) and sodium chloride. (1) In stress-relaxation experiments using a reciprocating tablet machine, none of the materials behaved as a Maxwell body in contrast to recent published work (David & Augsburger, 1977). Possible reasons for this disagreement are discussed. (2) Heckel plots showed that increasing the time for which a material was under compression (contact times of 0.17 and 10 s) had no effect on dicalcium phosphate compacts but increased the consolidation of other materials in the rank order sodium chloride less than lactose less than cellulose less than starch. (3) Deformation tests on preformed compacts were carried out in diametral compression by loading compacts to 75% of their breaking force at four different strain rates between 0.05 and 6.5 mm min-1. The deformation of Sta-Rx compacts was time-dependent. Sodium chloride compacts exhibited brittle behaviour in the diametral compression test and in the 10 s contact time experiment. This was apparently due to work-hardening, following the extensive plastic deformation of crystals during compaction as indicated by the stress relaxation results.", "contents": "Time-dependent deformation of some direct compression excipients. Three techniques were used to compare the time-dependent deformation of microfine cellulose (Elcema G250), anhydrous lactose, dicalcium phosphate dihydrate (Emcompress), modified starch (Sta-Rx 1500) and sodium chloride. (1) In stress-relaxation experiments using a reciprocating tablet machine, none of the materials behaved as a Maxwell body in contrast to recent published work (David & Augsburger, 1977). Possible reasons for this disagreement are discussed. (2) Heckel plots showed that increasing the time for which a material was under compression (contact times of 0.17 and 10 s) had no effect on dicalcium phosphate compacts but increased the consolidation of other materials in the rank order sodium chloride less than lactose less than cellulose less than starch. (3) Deformation tests on preformed compacts were carried out in diametral compression by loading compacts to 75% of their breaking force at four different strain rates between 0.05 and 6.5 mm min-1. The deformation of Sta-Rx compacts was time-dependent. Sodium chloride compacts exhibited brittle behaviour in the diametral compression test and in the 10 s contact time experiment. This was apparently due to work-hardening, following the extensive plastic deformation of crystals during compaction as indicated by the stress relaxation results."}
{"id": "PMID:30813", "title": "Phospholipase inactivation induced by an amino-piperazine derivative: a study at the lipid-water interface.", "content": "1-Amino-4-octylpiperazine, AP 22, an antiviral agent causes lipid accumulation in nervous tissue cultures. A physicochemical membrane model was used to demonstrate the formation of a lipid-AP 22 complex hindering phospholipase A2 action. A well defined amphiphilic balance seems essential to explain the mode of action of the drug. The hydrophilic group prevents enzyme-substrate complex formation whereas the hydrophobic group allows the penetration in the lipid layer and determines the stability of the drug-lipid complex. This stability of the drug-lipid association has a direct influence on phospholipase A2 activity but does not affect phospholipase C activity. No inactivation of phospholipase A2 due to a drug-enzyme interaction could be detected.", "contents": "Phospholipase inactivation induced by an amino-piperazine derivative: a study at the lipid-water interface. 1-Amino-4-octylpiperazine, AP 22, an antiviral agent causes lipid accumulation in nervous tissue cultures. A physicochemical membrane model was used to demonstrate the formation of a lipid-AP 22 complex hindering phospholipase A2 action. A well defined amphiphilic balance seems essential to explain the mode of action of the drug. The hydrophilic group prevents enzyme-substrate complex formation whereas the hydrophobic group allows the penetration in the lipid layer and determines the stability of the drug-lipid complex. This stability of the drug-lipid association has a direct influence on phospholipase A2 activity but does not affect phospholipase C activity. No inactivation of phospholipase A2 due to a drug-enzyme interaction could be detected."}
{"id": "PMID:30815", "title": "Baclofen (beta-p-chlorophenyl-gamma-aminobutyric acid) enhances [3H]gamma-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro.", "content": "The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic GABA mechanisms in vitro. (+/-)-Baclofen (300 micrometer-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with 3H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen: neither the (-)-isomer nor another neuronal depressant dl-alpha-epsilon-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither beta-phenethylamine nor dopamine evoked release of 3H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [3H]-beta-alanine or [3H]diaminobutyric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (beta-alanine and (+/-)-cis-1,3-amino-cyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [3H]GABA release. Baclofen also inhibited uptake of [3H]GABA into pallidal slices with an IC50 value of 6 x 10(-4) m. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (-)-isomer. The potential of the (+)-isomer as an antipsychotic agent while (-)-baclofen remains the effective antispastic drug free from unwanted side-effects, is discussed.", "contents": "Baclofen (beta-p-chlorophenyl-gamma-aminobutyric acid) enhances [3H]gamma-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro. The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic GABA mechanisms in vitro. (+/-)-Baclofen (300 micrometer-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with 3H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen: neither the (-)-isomer nor another neuronal depressant dl-alpha-epsilon-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither beta-phenethylamine nor dopamine evoked release of 3H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [3H]-beta-alanine or [3H]diaminobutyric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (beta-alanine and (+/-)-cis-1,3-amino-cyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [3H]GABA release. Baclofen also inhibited uptake of [3H]GABA into pallidal slices with an IC50 value of 6 x 10(-4) m. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (-)-isomer. The potential of the (+)-isomer as an antipsychotic agent while (-)-baclofen remains the effective antispastic drug free from unwanted side-effects, is discussed."}
{"id": "PMID:30816", "title": "The indirect sympathomimetic activity of etilefrine--a comparison with tyramine and ephedrine using [3H] noradrenaline.", "content": "The indirect sympathomimetic activity of etilefrine has been examined using the ventral caudal artery of the rat. This vessel has a rich sympathetic innervation and lends itself to studies on [3H]noradrenaline efflux from these sites. Etilefrine possessed significant indirect activity on the artery and this action, although less than that of tyramine, was equivalent to that caused by ephedrine. Pretreatment of the vessels with a mixture of iproniazid, doca, cocaine and UO521 (3',4'-dihydroxy-2-methyl propiophenone) significantly enhanced[3H]-noradrenaline efflux from the artery.", "contents": "The indirect sympathomimetic activity of etilefrine--a comparison with tyramine and ephedrine using [3H] noradrenaline. The indirect sympathomimetic activity of etilefrine has been examined using the ventral caudal artery of the rat. This vessel has a rich sympathetic innervation and lends itself to studies on [3H]noradrenaline efflux from these sites. Etilefrine possessed significant indirect activity on the artery and this action, although less than that of tyramine, was equivalent to that caused by ephedrine. Pretreatment of the vessels with a mixture of iproniazid, doca, cocaine and UO521 (3',4'-dihydroxy-2-methyl propiophenone) significantly enhanced[3H]-noradrenaline efflux from the artery."}
{"id": "PMID:30817", "title": "Differences in responsiveness to adipokinetic agents between white epididymal and brown interscapula adipose tissue from rats.", "content": "Lipolytic activity was studied in brown and white adipose tissue of rats in vitro. 5-Hydroxy-tryptamine (5-HT), phenylephrine, noradrenaline, adrenaline and isoprenaline were used as adipokinetic agents. All stimulated lipolysis in brown adipose tissue, but 5-HT and phenyl-ephrine did not in white adipose tissue. A beta-blocking drug, propranolol, inhibited the stimulatory effect of the agents in both adipose tissues. However, an alpha-blocking drug, phentolamine, further increased the lipolysis induced by noradrenaline or adrenaline in brown adipose tissue and inhibited the effect of isoprenaline. In white adipose tissue, its action was to marginally decrease the effect of adrenaline and noradrenaline. Increase in the pH of the incubation medium stimulated FFA and glycerol release in brown adipose tissue, but not in the epididymal adipose tissue. This effect of pH on lipolysis was further enhanced by phentolamine and decreased by propranolol. Increase of lipolysis with pH was not seen with brown fat tissue from the reserpine-treated rats. These results show that brown adipose tissue of the rat has an alpha-receptor with inhibitory effects on lipolysis that is affected by alpha- or mixed-type adrenergic agonists, noradrenaline and adrenaline.", "contents": "Differences in responsiveness to adipokinetic agents between white epididymal and brown interscapula adipose tissue from rats. Lipolytic activity was studied in brown and white adipose tissue of rats in vitro. 5-Hydroxy-tryptamine (5-HT), phenylephrine, noradrenaline, adrenaline and isoprenaline were used as adipokinetic agents. All stimulated lipolysis in brown adipose tissue, but 5-HT and phenyl-ephrine did not in white adipose tissue. A beta-blocking drug, propranolol, inhibited the stimulatory effect of the agents in both adipose tissues. However, an alpha-blocking drug, phentolamine, further increased the lipolysis induced by noradrenaline or adrenaline in brown adipose tissue and inhibited the effect of isoprenaline. In white adipose tissue, its action was to marginally decrease the effect of adrenaline and noradrenaline. Increase in the pH of the incubation medium stimulated FFA and glycerol release in brown adipose tissue, but not in the epididymal adipose tissue. This effect of pH on lipolysis was further enhanced by phentolamine and decreased by propranolol. Increase of lipolysis with pH was not seen with brown fat tissue from the reserpine-treated rats. These results show that brown adipose tissue of the rat has an alpha-receptor with inhibitory effects on lipolysis that is affected by alpha- or mixed-type adrenergic agonists, noradrenaline and adrenaline."}
{"id": "PMID:30818", "title": "The absorption of aliphatic carbamates from the rat colon.", "content": "The colonic absorptio n of a series of aliphatic carbamates has been studied using an in situ preparation in the rat. The absorption process appeared to be passive and no metabolism by the colon membrane was detected. A linear correlation between the logarithms of the absorption rate constants and apparent partition coefficients was found. The absorption rates were not affected by concurrent water flux.", "contents": "The absorption of aliphatic carbamates from the rat colon. The colonic absorptio n of a series of aliphatic carbamates has been studied using an in situ preparation in the rat. The absorption process appeared to be passive and no metabolism by the colon membrane was detected. A linear correlation between the logarithms of the absorption rate constants and apparent partition coefficients was found. The absorption rates were not affected by concurrent water flux."}
{"id": "PMID:30835", "title": "Mechanism of fluorometric analysis of tetracycline involving metal complexation.", "content": "Tetracycline complexation with calcium and organic ligands was studied using fluorescence, circular dichroism, and solvent extraction methods. The results were used to interpret the mechanism of the commonly used fluorometric methods for the analysis of tetracycline in biological fluids. Tetracycline formed ternary calcium complexes with barbital sodium and L-tryptophan in alkaline solutions. The circular dichroism studies indicate that the calcium ion in these complexes is bound to the C-4 dimethylamino and the C-12a hydroxyl groups of tetracycline. These ternary complexes are strongly fluorescent and can be extracted easily into 1-butanol or ethyl acetate. Based on the characteristics of the ternary complexes and of the tetracycline degradation products, it is concluded that only the active form of tetracycline can be complexed and extracted for fluorescence analysis.", "contents": "Mechanism of fluorometric analysis of tetracycline involving metal complexation. Tetracycline complexation with calcium and organic ligands was studied using fluorescence, circular dichroism, and solvent extraction methods. The results were used to interpret the mechanism of the commonly used fluorometric methods for the analysis of tetracycline in biological fluids. Tetracycline formed ternary calcium complexes with barbital sodium and L-tryptophan in alkaline solutions. The circular dichroism studies indicate that the calcium ion in these complexes is bound to the C-4 dimethylamino and the C-12a hydroxyl groups of tetracycline. These ternary complexes are strongly fluorescent and can be extracted easily into 1-butanol or ethyl acetate. Based on the characteristics of the ternary complexes and of the tetracycline degradation products, it is concluded that only the active form of tetracycline can be complexed and extracted for fluorescence analysis."}
{"id": "PMID:30836", "title": "Degradative behavior of a new bronchodilator, carbuterol, in aqueous solution.", "content": "The degradation kinetics of carbuterol in aqueous solution were investigated at 85 degrees and constant ionic strength over the pH 0.25--13.3 range under anaerobic conditions. The results demonstrated a complex kinetic pattern involving specific acid and specific base catalyses at the pH extremes. Degradation resulted primarily from intramolecular catalysis and indicated that both the protonated and unprotonated phenolic groups participated in the reaction. High-pressure liquid chromatography was used to isolate carbuterol and its degradation product. Mass spectrometric examination showed that the degradation product was a cyclized derivative formed by intramolecular attack of the phenoxy group on the ureido carbonyl with ammonia expulsion. The apparent activation energy for carbuterol at pH 4.0 and 10.0 was 22.3 and 11.7 kcal/mole, respectively. The agreement between the calculated theoretical pH--rate profile and the experimental points supports the hypothesis presented concerning the reactions involved in carbuterol degradation.", "contents": "Degradative behavior of a new bronchodilator, carbuterol, in aqueous solution. The degradation kinetics of carbuterol in aqueous solution were investigated at 85 degrees and constant ionic strength over the pH 0.25--13.3 range under anaerobic conditions. The results demonstrated a complex kinetic pattern involving specific acid and specific base catalyses at the pH extremes. Degradation resulted primarily from intramolecular catalysis and indicated that both the protonated and unprotonated phenolic groups participated in the reaction. High-pressure liquid chromatography was used to isolate carbuterol and its degradation product. Mass spectrometric examination showed that the degradation product was a cyclized derivative formed by intramolecular attack of the phenoxy group on the ureido carbonyl with ammonia expulsion. The apparent activation energy for carbuterol at pH 4.0 and 10.0 was 22.3 and 11.7 kcal/mole, respectively. The agreement between the calculated theoretical pH--rate profile and the experimental points supports the hypothesis presented concerning the reactions involved in carbuterol degradation."}
{"id": "PMID:30837", "title": "Mechanism of hydrolysis of halogenated nitrosoureas.", "content": "The hydrolysis kinetics of halogenated nitrosoureas were investigated using chlorozotocin as a model. Evidence is presented to show that the hydrolytic reaction of halogenated nitrosoureas between pH 3 and 8 is a summation of spontaneous water and hydroxide-ion-catalyzed reactions; the later reaction is the sum of two parallel reactions. The relative contribuiton of each reaction changes with pH and results in different product distributions. Dianionic phosphate (HPO42-) increased the amount of free chloride-ion production without significantly altering the hydrolysis rate. A mechanism is proposed to explain this behavior. The role of hydrolytic decomposition products produced at physiological pH on the biological activity of nitrosoureas is discussed.", "contents": "Mechanism of hydrolysis of halogenated nitrosoureas. The hydrolysis kinetics of halogenated nitrosoureas were investigated using chlorozotocin as a model. Evidence is presented to show that the hydrolytic reaction of halogenated nitrosoureas between pH 3 and 8 is a summation of spontaneous water and hydroxide-ion-catalyzed reactions; the later reaction is the sum of two parallel reactions. The relative contribuiton of each reaction changes with pH and results in different product distributions. Dianionic phosphate (HPO42-) increased the amount of free chloride-ion production without significantly altering the hydrolysis rate. A mechanism is proposed to explain this behavior. The role of hydrolytic decomposition products produced at physiological pH on the biological activity of nitrosoureas is discussed."}
{"id": "PMID:30838", "title": "Potential antitumor agents via inhibitors of L-asparagine synthetase: substituted sulfonamides and sulfonyl hydrazides related to glutamine.", "content": "A series of 4-(substituted aminosulfonyl)- and 4-(substituted hydrazinosulfonyl)-2-aminobutanoic acids, compounds structurally related to glutamine, was synthesized as potential inhibitors of L-asparagine synthetase and subjected to screening as antitumor agents. Target amino acids were obtained by condensation of a blocked reactive sulfonyl chloride with the appropriate amine or hydrazide, followed by deblocking with hydrogen--palladium or liquid hydrogen fluoride--anisole. Neither the target compounds nor their protected precursors inhibited the enzyme from L5178Y/AR or prolonged the life of mice with P-388 lymphocytic leukemia. However, DL-4,4'-dithiobis[2-(benzyloxycarbonylamino)butanoic acid], an intermediate in the synthesis of the target amino acids, exhibited 90% inhibition of L-asparagine synthetase at 10 mM.", "contents": "Potential antitumor agents via inhibitors of L-asparagine synthetase: substituted sulfonamides and sulfonyl hydrazides related to glutamine. A series of 4-(substituted aminosulfonyl)- and 4-(substituted hydrazinosulfonyl)-2-aminobutanoic acids, compounds structurally related to glutamine, was synthesized as potential inhibitors of L-asparagine synthetase and subjected to screening as antitumor agents. Target amino acids were obtained by condensation of a blocked reactive sulfonyl chloride with the appropriate amine or hydrazide, followed by deblocking with hydrogen--palladium or liquid hydrogen fluoride--anisole. Neither the target compounds nor their protected precursors inhibited the enzyme from L5178Y/AR or prolonged the life of mice with P-388 lymphocytic leukemia. However, DL-4,4'-dithiobis[2-(benzyloxycarbonylamino)butanoic acid], an intermediate in the synthesis of the target amino acids, exhibited 90% inhibition of L-asparagine synthetase at 10 mM."}
{"id": "PMID:30839", "title": "Hemolytic properties of synthetic glycosides.", "content": "Cholesteryl alpha-L-rhamnopyranoside, tigogenyl alpha-L-rhamnopyranoside, tigogenyl beta-D-fucopyranoside, smilagenyl beta-D-fucopyranoside, cholesteryl beta-maltoside, tigogenyl beta-maltoside, and smilagenyl beta-maltoside were synthesized and characterized. The rhamnosides and fucosides, as well as some other steroid monoglycosides, proved to be extremely insoluble in water. The concentration giving 50% hemolysis, H50, was of the same order of magnitude for all synthetic glycosides. Ghost cells collected from blood hemolyzed by smilagenyl maltoside and tigogenyl maltoside had appreciable amounts of absorbed aglycones. All results are in accordance with previous investigations on the mechanism of saponin and sapogenin hemolysis.", "contents": "Hemolytic properties of synthetic glycosides. Cholesteryl alpha-L-rhamnopyranoside, tigogenyl alpha-L-rhamnopyranoside, tigogenyl beta-D-fucopyranoside, smilagenyl beta-D-fucopyranoside, cholesteryl beta-maltoside, tigogenyl beta-maltoside, and smilagenyl beta-maltoside were synthesized and characterized. The rhamnosides and fucosides, as well as some other steroid monoglycosides, proved to be extremely insoluble in water. The concentration giving 50% hemolysis, H50, was of the same order of magnitude for all synthetic glycosides. Ghost cells collected from blood hemolyzed by smilagenyl maltoside and tigogenyl maltoside had appreciable amounts of absorbed aglycones. All results are in accordance with previous investigations on the mechanism of saponin and sapogenin hemolysis."}
{"id": "PMID:30840", "title": "Intrinsic factor-mediated binding of cyanocobalamin to cholestyramine.", "content": "The intrinsic factor-mediated binding of cyanocobalamin to cholestyramine was studied in vitro under varying conditions of pH, added electrolyte, and bile salt. The intrinsic factor-cyanocobalamin complex was adsorbed strongly by the resin at pH 3 in the presence of neutral salt and low concentrations of glycocholic acid. An increase in glycocholic acid concentration as well as neutral pH decreased the observed binding, although significant amounts of cyanocobalamin-intrinsic factor complex remained bound after incubation at pH 6.8. Cyanocobalamin alone was not adsorbed by the resin.", "contents": "Intrinsic factor-mediated binding of cyanocobalamin to cholestyramine. The intrinsic factor-mediated binding of cyanocobalamin to cholestyramine was studied in vitro under varying conditions of pH, added electrolyte, and bile salt. The intrinsic factor-cyanocobalamin complex was adsorbed strongly by the resin at pH 3 in the presence of neutral salt and low concentrations of glycocholic acid. An increase in glycocholic acid concentration as well as neutral pH decreased the observed binding, although significant amounts of cyanocobalamin-intrinsic factor complex remained bound after incubation at pH 6.8. Cyanocobalamin alone was not adsorbed by the resin."}
{"id": "PMID:30841", "title": "Antagonism by naloxone of narcotic-induced respiratory depression and analgesia.", "content": "Receptor mechanisms for narcotic-induced respiratory depression and analgesia were compared by apparent pA2 values of morphine-naloxone, levorphanol-naloxone and pentazocine-naloxone. The similarity of apparent pA2 values of the three compunds for respiratory depression suggests that morphine, levorphanol and pentazocine may interact with similar receptors to produce this effect. Significant differences between apparent pA2 values of pentazocine-naloxone and morphine-naloxone or levor-phanol-naloxone for analgesia suggest, as previously shown, that narcotic and narcotic-antagonist analgesics appear to interact with receptors in different manners. Significant differences between apparent pA2 values for respiratory depression and analgesia suggest that these two effects of the narcotic drugs are mediated by different receptor interactions.", "contents": "Antagonism by naloxone of narcotic-induced respiratory depression and analgesia. Receptor mechanisms for narcotic-induced respiratory depression and analgesia were compared by apparent pA2 values of morphine-naloxone, levorphanol-naloxone and pentazocine-naloxone. The similarity of apparent pA2 values of the three compunds for respiratory depression suggests that morphine, levorphanol and pentazocine may interact with similar receptors to produce this effect. Significant differences between apparent pA2 values of pentazocine-naloxone and morphine-naloxone or levor-phanol-naloxone for analgesia suggest, as previously shown, that narcotic and narcotic-antagonist analgesics appear to interact with receptors in different manners. Significant differences between apparent pA2 values for respiratory depression and analgesia suggest that these two effects of the narcotic drugs are mediated by different receptor interactions."}
{"id": "PMID:30849", "title": "The effect of beta adrenergic receptor blockade on the renin response to respiratory acidosis.", "content": "The effect of beta adrenergic blockade on the increase in plasma renin activity produced by acute respiratory acidosis was studied in chloralose anesthetized dogs. Sixteen mongrel dogs were given 4%, 8% and 12% CO2 in room air, successively. Propranolol (2 mg/Kg) was given to 8 dogs prior to CO2 inhalation. The other 8 dogs served as the control group. The response of elevated plasma renin activity during 4% and 8% CO2 inhalation was not different between the control and propranolol groups. However, the increase of plasma renin activity in the control group was greater than that of the propranolol treated group during 12% CO2 inhalation. It is suggested that activation of beta adrenergic receptors is not the sole factor in renin control during acute respiratory acidosis, although these receptors do mediate a significant fraction of the renin response to CO2 inhalation.", "contents": "The effect of beta adrenergic receptor blockade on the renin response to respiratory acidosis. The effect of beta adrenergic blockade on the increase in plasma renin activity produced by acute respiratory acidosis was studied in chloralose anesthetized dogs. Sixteen mongrel dogs were given 4%, 8% and 12% CO2 in room air, successively. Propranolol (2 mg/Kg) was given to 8 dogs prior to CO2 inhalation. The other 8 dogs served as the control group. The response of elevated plasma renin activity during 4% and 8% CO2 inhalation was not different between the control and propranolol groups. However, the increase of plasma renin activity in the control group was greater than that of the propranolol treated group during 12% CO2 inhalation. It is suggested that activation of beta adrenergic receptors is not the sole factor in renin control during acute respiratory acidosis, although these receptors do mediate a significant fraction of the renin response to CO2 inhalation."}
{"id": "PMID:30853", "title": "[Comparative characteristics of various anti-arrhythmia agents used under clinical conditions].", "content": "Comparative clinical and experimental study of the efficacy of the currently used anti-arrhythmic agents was conducted on 610 patients (828 cases) with various disorders of the cardiac rhythm. The modern classification of these agents is given. The indications and contra-indications for the prescription of the drugs, the optimum doses, and the routes of administration are discussed. Differentiated therapy in various disorders of the cardiac rhythm is recommended.", "contents": "[Comparative characteristics of various anti-arrhythmia agents used under clinical conditions]. Comparative clinical and experimental study of the efficacy of the currently used anti-arrhythmic agents was conducted on 610 patients (828 cases) with various disorders of the cardiac rhythm. The modern classification of these agents is given. The indications and contra-indications for the prescription of the drugs, the optimum doses, and the routes of administration are discussed. Differentiated therapy in various disorders of the cardiac rhythm is recommended."}
{"id": "PMID:30855", "title": "[Serumconcentrations of non esterified fatty acids during operative stress and blockade of betaadrenergic receptors (author's transl)].", "content": "Every stress reaction leads to an increased, hormonelly induced mobilisation of fatty acids, the extent of which may be considered as a parameter of the aggression mechanism. In 15 patients with idiopathic trigeminal neuralgia, who were operated under neurolepthypalgesia, the problem of quantitative alterations of the concentration pattern of fatty acids was investigated during the operation. In contrast to some reports of the literature, the increase of the concentration of total fatty acids was due to corresponding increases of all individual fatty acids. By preoperative administration of the beta-adrenergic blocking agent Pindolol the increase of fatty acids was reduced without a qualitative shifting of individual fatty acids.", "contents": "[Serumconcentrations of non esterified fatty acids during operative stress and blockade of betaadrenergic receptors (author's transl)]. Every stress reaction leads to an increased, hormonelly induced mobilisation of fatty acids, the extent of which may be considered as a parameter of the aggression mechanism. In 15 patients with idiopathic trigeminal neuralgia, who were operated under neurolepthypalgesia, the problem of quantitative alterations of the concentration pattern of fatty acids was investigated during the operation. In contrast to some reports of the literature, the increase of the concentration of total fatty acids was due to corresponding increases of all individual fatty acids. By preoperative administration of the beta-adrenergic blocking agent Pindolol the increase of fatty acids was reduced without a qualitative shifting of individual fatty acids."}
{"id": "PMID:30856", "title": "[The importance of changes in whole-body balance of sodium and noradrenaline in essential hypertension (author's transl)].", "content": "In 22 patients with essential hypertension plasma levels and urine excretions of sodium and noradrenaline were studied before, during and after long-term beta-blockade with pindolol. The relation between mean blood pressure and the quotient of sodium-/noradrenaline-excretion changed during treatment (placebo r=-0.34; pindolol r=+0.31). During placebo there existed a significant (p is less than 0.03) correlation between blood pressure and sodium-excretion which disappeared during beta-blockade. No correlation between blood pressure and noradrenaline was seen during placebo, whereas during beta-blockade a significant (p is less than 0.003) correlation was observed. In contrast to the placebo period there was a significant positive correlation between sodium- and noradrenaline-excretion during long-term treatment with pindolol. It is concluded that whole-body balance of sodium and noradrenaline is an important factor in essential hypertension.", "contents": "[The importance of changes in whole-body balance of sodium and noradrenaline in essential hypertension (author's transl)]. In 22 patients with essential hypertension plasma levels and urine excretions of sodium and noradrenaline were studied before, during and after long-term beta-blockade with pindolol. The relation between mean blood pressure and the quotient of sodium-/noradrenaline-excretion changed during treatment (placebo r=-0.34; pindolol r=+0.31). During placebo there existed a significant (p is less than 0.03) correlation between blood pressure and sodium-excretion which disappeared during beta-blockade. No correlation between blood pressure and noradrenaline was seen during placebo, whereas during beta-blockade a significant (p is less than 0.003) correlation was observed. In contrast to the placebo period there was a significant positive correlation between sodium- and noradrenaline-excretion during long-term treatment with pindolol. It is concluded that whole-body balance of sodium and noradrenaline is an important factor in essential hypertension."}
{"id": "PMID:30857", "title": "[In vitro evaluation of adsorbents used in haemoperfusion (author's transl)].", "content": "The properties of six adsorbents for Haemoperfusion were investigated in vitro: Amberlite XAD-2; Amberlite XAD-4; Haemocol; collodion coated charcoal; albumine-collodion encapsulated charcoal and activated carbon fibers. Carbromal and diazepam are most quickly removed from aqueous solutions by Amberlite XAD-2 and XAD-4. Of the charcoal containing materials, Haemocol eliminates most rapidly carbromal and diazepam; while activated carbon fibers remove phenobarbital faster. When heparinized blood is perfused, a remarkable reduction in platelet count is observed. The drop is most pronounced with Amberlite XAD-2 and XAD-4, but even when using charcoal preparations the platelet depletion can reach 10% of the original number over 5 hours. Haemolysis is most pronounced with Amberlite XAD-2, XAD-4 and Haemocol. As the efficiency of the adsorbents towards the various drugs differ and as their adverse effects also vary, the decision for a particular material will have to be made according to the individual case.", "contents": "[In vitro evaluation of adsorbents used in haemoperfusion (author's transl)]. The properties of six adsorbents for Haemoperfusion were investigated in vitro: Amberlite XAD-2; Amberlite XAD-4; Haemocol; collodion coated charcoal; albumine-collodion encapsulated charcoal and activated carbon fibers. Carbromal and diazepam are most quickly removed from aqueous solutions by Amberlite XAD-2 and XAD-4. Of the charcoal containing materials, Haemocol eliminates most rapidly carbromal and diazepam; while activated carbon fibers remove phenobarbital faster. When heparinized blood is perfused, a remarkable reduction in platelet count is observed. The drop is most pronounced with Amberlite XAD-2 and XAD-4, but even when using charcoal preparations the platelet depletion can reach 10% of the original number over 5 hours. Haemolysis is most pronounced with Amberlite XAD-2, XAD-4 and Haemocol. As the efficiency of the adsorbents towards the various drugs differ and as their adverse effects also vary, the decision for a particular material will have to be made according to the individual case."}
{"id": "PMID:30858", "title": "[Composition of the trace contaminants in the atmosphere of the Soiuz-22 space ship].", "content": "The Soyuz-22 space cabin atmosphere was studied for volatile organic trace contaminants. By gas chromatography the following constituents were identified: methane, ethane, heptane, methanol, ethanol, n-propanol, acetaldehyde, acetone, ethyl benzene. Except for acetone, concentrations of the above compounds were close to the values determined in the mock-up experiments.", "contents": "[Composition of the trace contaminants in the atmosphere of the Soiuz-22 space ship]. The Soyuz-22 space cabin atmosphere was studied for volatile organic trace contaminants. By gas chromatography the following constituents were identified: methane, ethane, heptane, methanol, ethanol, n-propanol, acetaldehyde, acetone, ethyl benzene. Except for acetone, concentrations of the above compounds were close to the values determined in the mock-up experiments."}
{"id": "PMID:30868", "title": "The pediatric nurse practitioner: origins and challenges.", "content": "During the past decade, a new health professional has evolved--the pediatric nurse practitioner (PNP). Responding to warnings of a shortage of primary care physicians, the American Academy of Pediatrics helped encourage programs to train PNPs who would provide well-child care, working under a physician's supervision. Simultaneously, in response to changing attitudes by and toward nurses, the American Nurses' Association expressed support for the expanded role of nurses in direct patient care functions--an expansion that would supplement other new academic programs in advancing the status of nursing as an interdependent, rather than subsidiary, health profession. Although mutually aiming at improvements in health care, both professions thus acted with different motivations and goals that have produced ongoing conflicts. These conflicts have been intensified by the absence of long-range planning in federal programs that have supported training for nurse practitioners. This paper summarizes the history of the PNP movement and the unresolved problems created by this new health professional.", "contents": "The pediatric nurse practitioner: origins and challenges. During the past decade, a new health professional has evolved--the pediatric nurse practitioner (PNP). Responding to warnings of a shortage of primary care physicians, the American Academy of Pediatrics helped encourage programs to train PNPs who would provide well-child care, working under a physician's supervision. Simultaneously, in response to changing attitudes by and toward nurses, the American Nurses' Association expressed support for the expanded role of nurses in direct patient care functions--an expansion that would supplement other new academic programs in advancing the status of nursing as an interdependent, rather than subsidiary, health profession. Although mutually aiming at improvements in health care, both professions thus acted with different motivations and goals that have produced ongoing conflicts. These conflicts have been intensified by the absence of long-range planning in federal programs that have supported training for nurse practitioners. This paper summarizes the history of the PNP movement and the unresolved problems created by this new health professional."}
{"id": "PMID:30880", "title": "Transport capacity, alkaline phosphatase activity and protein content of glutaraldehyde-treated cell forms of Escherichia coli.", "content": "Studies on the comparative transport capacity of various cell forms of Escherichia coli suggest that glutaraldehyde acts only in the outer regions of the cell envelope and to such an extent that transport of alpha-aminoisobutyric acid is reduced by 50%. Alkaline phosphatase activity in whole cells was severely impaired in the presence of alkaline glutaraldehyde and in NaCl-washed cells both acid and alkaline glutaraldehyde (0.01%) caused approximately 80-90% reduction in enzyme activity in 10 min. Protein content was reduced by only 10-15% with this concentration of glutaraldehyde, and cell volume decreased by the same extent. These results are discussed in terms of the mode of action of the disinfectant.", "contents": "Transport capacity, alkaline phosphatase activity and protein content of glutaraldehyde-treated cell forms of Escherichia coli. Studies on the comparative transport capacity of various cell forms of Escherichia coli suggest that glutaraldehyde acts only in the outer regions of the cell envelope and to such an extent that transport of alpha-aminoisobutyric acid is reduced by 50%. Alkaline phosphatase activity in whole cells was severely impaired in the presence of alkaline glutaraldehyde and in NaCl-washed cells both acid and alkaline glutaraldehyde (0.01%) caused approximately 80-90% reduction in enzyme activity in 10 min. Protein content was reduced by only 10-15% with this concentration of glutaraldehyde, and cell volume decreased by the same extent. These results are discussed in terms of the mode of action of the disinfectant."}
{"id": "PMID:30881", "title": "Physico-chemical properties of mouse hepatitis virus (MHV-2) grown on DBT cell culture.", "content": "Some properties of a strain of mouse hepatitis virus, MHV-2, grown on DBT cells were determined using a plaque assay on the cells. Viral growth was not inhibited by the presence of actinomycin D or 5-iodo-2-deoxyuridine. MHV-2 was completely inactivated by ether, chloroform, sodium deoxycholate or beta-propiolactone, but showed a moderate resistance to trypsin. Heating at 56 C for 30 min did not completely abolish the virus infectivity. The virus was stable after heating at 50 C for 15 min in 1M-MgCl2 or 1M-MgSO4 as well as at 37 C for 60 min at pH 3.0 to 9.0. Infectivity was decreased to 1/100 and 1/400 after storing at 4 C for 30 days and 37 C for 24 hr, respectively. The virus passed through a 200-nm but not a 50-nm Sartorius membrane filter. The buoyant density of MHV-2 was 1.183 g/cm3 in sucrose gradient, and the fraction contained coronavirus-like particles measuring 70 to 130 nm in diameter. Survival rate was 10% after exposure to ultraviolet at 150 ergs/mm2. Freezing and thawing or sonication at 20 kc for 3 min did not affect the virus titer. No hemagglutinin was demonstrable with red blood cells of the chicken, Japanese quail, mouse, rat, hamster, guinea pig, sheep, bovine or human.", "contents": "Physico-chemical properties of mouse hepatitis virus (MHV-2) grown on DBT cell culture. Some properties of a strain of mouse hepatitis virus, MHV-2, grown on DBT cells were determined using a plaque assay on the cells. Viral growth was not inhibited by the presence of actinomycin D or 5-iodo-2-deoxyuridine. MHV-2 was completely inactivated by ether, chloroform, sodium deoxycholate or beta-propiolactone, but showed a moderate resistance to trypsin. Heating at 56 C for 30 min did not completely abolish the virus infectivity. The virus was stable after heating at 50 C for 15 min in 1M-MgCl2 or 1M-MgSO4 as well as at 37 C for 60 min at pH 3.0 to 9.0. Infectivity was decreased to 1/100 and 1/400 after storing at 4 C for 30 days and 37 C for 24 hr, respectively. The virus passed through a 200-nm but not a 50-nm Sartorius membrane filter. The buoyant density of MHV-2 was 1.183 g/cm3 in sucrose gradient, and the fraction contained coronavirus-like particles measuring 70 to 130 nm in diameter. Survival rate was 10% after exposure to ultraviolet at 150 ergs/mm2. Freezing and thawing or sonication at 20 kc for 3 min did not affect the virus titer. No hemagglutinin was demonstrable with red blood cells of the chicken, Japanese quail, mouse, rat, hamster, guinea pig, sheep, bovine or human."}
{"id": "PMID:30887", "title": "Loss of the sole.", "content": "The sole of the foot in a wood merchant was lost when he trod on a circular saw which had been placed on the ground. The foot was resurfaced by immediate split skin grafts, and the result proved very satisfactory. The immediate grafting procedure took on the cancellous bone, and as an emergency procedure it is recommended while thought is being given to more elaborate procedures such as cross leg flap grafts or even amputation.", "contents": "Loss of the sole. The sole of the foot in a wood merchant was lost when he trod on a circular saw which had been placed on the ground. The foot was resurfaced by immediate split skin grafts, and the result proved very satisfactory. The immediate grafting procedure took on the cancellous bone, and as an emergency procedure it is recommended while thought is being given to more elaborate procedures such as cross leg flap grafts or even amputation."}
{"id": "PMID:30882", "title": "[Fixation of free nitrogen in the soil and on the roots of citrus trees in the subtropics of the Georgian SSR].", "content": "The rate of biological nitrogen fixation was determined by the acetylene technique in soils and on the roots of orange, mandarin and lemon trees growing in red, yellow, podzolic, alluvial brown forest, and humus-calcareous soils. The minimum nitrogen fixation in podzolic soils was 3--8 kg of nitrogen per hectare per vegetative period. The maximum nitrogen fixation (48--51 kg N per hectare) was found in red and humus-calcareous soils of orange plantations. One dose of nitrogen fertilizers with liming increased the nitrogen fixing activity of subtropic podzolic soils of mandarin plantations whereas a triple dose inhibited the activity. The rate of nitrogen fixation by the root microflora was 3--4 times higher than that by the soil microflora.", "contents": "[Fixation of free nitrogen in the soil and on the roots of citrus trees in the subtropics of the Georgian SSR]. The rate of biological nitrogen fixation was determined by the acetylene technique in soils and on the roots of orange, mandarin and lemon trees growing in red, yellow, podzolic, alluvial brown forest, and humus-calcareous soils. The minimum nitrogen fixation in podzolic soils was 3--8 kg of nitrogen per hectare per vegetative period. The maximum nitrogen fixation (48--51 kg N per hectare) was found in red and humus-calcareous soils of orange plantations. One dose of nitrogen fertilizers with liming increased the nitrogen fixing activity of subtropic podzolic soils of mandarin plantations whereas a triple dose inhibited the activity. The rate of nitrogen fixation by the root microflora was 3--4 times higher than that by the soil microflora."}
{"id": "PMID:30883", "title": "[DNA synthesis and degradation in the cells of Bacillus stearothermophilus].", "content": "ATP-dependent and ATP-independent synthesis of DNA was studied on nucleotide-permeable cells of Bacillus stearothermophilus. The effect of temperature, pH, ionic strength, and bivalent metal ions on both types of DNA synthesis was investigated as well as their susceptibility to an SH-blocking agent. The level of ATP-independent synthesis of DNA in the cells of Bac. stearothermophilus was found to be ten times higher than that in E. coli. In the semipermeable cells of Bac. stearothermophilus, 90% of DNA of the chromosome was accessible to their nucleases. The temperature optimum of the activity of DNA polymerases and nucleases in the cells treated with toluene coincided with the optimum of the bacterial growth.", "contents": "[DNA synthesis and degradation in the cells of Bacillus stearothermophilus]. ATP-dependent and ATP-independent synthesis of DNA was studied on nucleotide-permeable cells of Bacillus stearothermophilus. The effect of temperature, pH, ionic strength, and bivalent metal ions on both types of DNA synthesis was investigated as well as their susceptibility to an SH-blocking agent. The level of ATP-independent synthesis of DNA in the cells of Bac. stearothermophilus was found to be ten times higher than that in E. coli. In the semipermeable cells of Bac. stearothermophilus, 90% of DNA of the chromosome was accessible to their nucleases. The temperature optimum of the activity of DNA polymerases and nucleases in the cells treated with toluene coincided with the optimum of the bacterial growth."}
{"id": "PMID:30884", "title": "[Exoprotease properties of Bacillus subtilis var. amyloliquefaciens capable of coagulating blood plasma].", "content": "The properties of the homogeneous exoprotease preparation from Bacillus subtilis varamyloliquefaciens 759 possessing the coagulase activity were studied. The enzyme is an alkaline protease, has the isopoint at pH 7.8, and not only clots blood plasmo but also hydrolyses such protein substrates as casein, hemoglobin, fibrinogen and fibrin. The enzyme is relatively stable at pH 6.0--9.0. Bivalent metal ions have virtually no effect on the enzyme activity though some of them stabilize it. The inhibitors PCMB and EDTA do not affect the activity of the enzyme whereas diisopropylfluorophosphate completely inactivates it. Fibrinogen is clotted by the enzyme only in the presence of blood plasma factors.", "contents": "[Exoprotease properties of Bacillus subtilis var. amyloliquefaciens capable of coagulating blood plasma]. The properties of the homogeneous exoprotease preparation from Bacillus subtilis varamyloliquefaciens 759 possessing the coagulase activity were studied. The enzyme is an alkaline protease, has the isopoint at pH 7.8, and not only clots blood plasmo but also hydrolyses such protein substrates as casein, hemoglobin, fibrinogen and fibrin. The enzyme is relatively stable at pH 6.0--9.0. Bivalent metal ions have virtually no effect on the enzyme activity though some of them stabilize it. The inhibitors PCMB and EDTA do not affect the activity of the enzyme whereas diisopropylfluorophosphate completely inactivates it. Fibrinogen is clotted by the enzyme only in the presence of blood plasma factors."}
{"id": "PMID:30893", "title": "[Toxico-analytical study of tofizopam].", "content": "For the legal-toxicological identification on the Grandaxin--a new minor tranquillant of benzodiazepine type--a new method have been worked out. Identification by layer-chromatography and determination by UV-spectrophotometry appeared to be suitable for the study of 5 postmortal cases.", "contents": "[Toxico-analytical study of tofizopam]. For the legal-toxicological identification on the Grandaxin--a new minor tranquillant of benzodiazepine type--a new method have been worked out. Identification by layer-chromatography and determination by UV-spectrophotometry appeared to be suitable for the study of 5 postmortal cases."}
{"id": "PMID:30885", "title": "[Dehydrogenase isoenzymatic spectrum of alanine, aspartic and glutamic acids in Candida albicans yeasts].", "content": "The isoenzyme spectrum of dehydrogenases of alanine, aspartic and glutamic acids requiring NAD and NADP  as cofactors was studied in Candida albicans. The spectrum of aspartate dehydrogenase was found to depend on a cofactor being used. The isoenzyme systems are related to proteins which posess various physico-chemical and antigenic properties.", "contents": "[Dehydrogenase isoenzymatic spectrum of alanine, aspartic and glutamic acids in Candida albicans yeasts]. The isoenzyme spectrum of dehydrogenases of alanine, aspartic and glutamic acids requiring NAD and NADP  as cofactors was studied in Candida albicans. The spectrum of aspartate dehydrogenase was found to depend on a cofactor being used. The isoenzyme systems are related to proteins which posess various physico-chemical and antigenic properties."}
{"id": "PMID:30886", "title": "[Acidophilic obligate thermophilic bacteria, Bacillus acidocal-darius, isolated from the hot springs and soil of Kunashir Island].", "content": "Obligate thermophilic acidophilic cultures of Bacillus acidocaldarius were isolated from hot springs and soil of the Kunashir Island (the Kuril Islands) and Southern Sakhalin; their optimum temperature of growth is 65 degrees C and pH is 3.3--4.0. It has been shown for the first time that these organisms can be isolated from springs with either acidic or neutral and weakly alkaline pH values.", "contents": "[Acidophilic obligate thermophilic bacteria, Bacillus acidocal-darius, isolated from the hot springs and soil of Kunashir Island]. Obligate thermophilic acidophilic cultures of Bacillus acidocaldarius were isolated from hot springs and soil of the Kunashir Island (the Kuril Islands) and Southern Sakhalin; their optimum temperature of growth is 65 degrees C and pH is 3.3--4.0. It has been shown for the first time that these organisms can be isolated from springs with either acidic or neutral and weakly alkaline pH values."}
{"id": "PMID:30911", "title": "Defining the histamine H2-receptor in brain: the interaction with LSD.", "content": "Two aspects of the complexities of the mode of action of drugs are described. One is the criteria and pitfalls of defining the interaction with specific receptors. The other is the need to consider each of the pharmacological effects of a drug as a  concatenation of receptor events, because it has become clear that each drug may have substantial affinity for many specific receptors. Illustrating these ideas is a characterization of the histamine receptor linked to adenylate cyclase in brain. The activities of a series of H2-antagonists and H2-agaonists were shown to be the same on the histamine receptor linked to adenylate cyclase as on known H2-receptors. The KB values of antagonists and ED50 values of agonists were not distinguishable among these receptors. Notably, at high concentrations, the H1-antagonists are also competitive antagonists of the H2-receptor. Cyproheptadine has especially high affinity for the H2-receptor. It is the most potent H2-antagonist yet reported. Other published results are reviewed to show the variety of receptors that cyproheptadine has affinity for. Its affinity for serotonin receptors led us to examine other serotonin antagonists. On this H2-receptor linked to adenylate cyclase in homogenates of guinea pig hippocampus and cortex, D-LSD and D-2-bromo-LSD (BrLSD) were shown to be competitive antagonists of histamine. L-LSD, mescaline and psilocin were inactive. Noting congurency in the molecular structyre of D-LSD and known H2-antagonists, we predicted a new H2-antagonist. This prediction is shown to be correct: the compound has similar affinity to the H2-receptor as has LSD. The affinities of D-LSD and BrLSD for the H2-receptor are compared with their affinities for other receptors. The pharmacology of D-LSD and BrLSD is reviewed. Evidence is assembled that BrLSD has considerable central effects.", "contents": "Defining the histamine H2-receptor in brain: the interaction with LSD. Two aspects of the complexities of the mode of action of drugs are described. One is the criteria and pitfalls of defining the interaction with specific receptors. The other is the need to consider each of the pharmacological effects of a drug as a  concatenation of receptor events, because it has become clear that each drug may have substantial affinity for many specific receptors. Illustrating these ideas is a characterization of the histamine receptor linked to adenylate cyclase in brain. The activities of a series of H2-antagonists and H2-agaonists were shown to be the same on the histamine receptor linked to adenylate cyclase as on known H2-receptors. The KB values of antagonists and ED50 values of agonists were not distinguishable among these receptors. Notably, at high concentrations, the H1-antagonists are also competitive antagonists of the H2-receptor. Cyproheptadine has especially high affinity for the H2-receptor. It is the most potent H2-antagonist yet reported. Other published results are reviewed to show the variety of receptors that cyproheptadine has affinity for. Its affinity for serotonin receptors led us to examine other serotonin antagonists. On this H2-receptor linked to adenylate cyclase in homogenates of guinea pig hippocampus and cortex, D-LSD and D-2-bromo-LSD (BrLSD) were shown to be competitive antagonists of histamine. L-LSD, mescaline and psilocin were inactive. Noting congurency in the molecular structyre of D-LSD and known H2-antagonists, we predicted a new H2-antagonist. This prediction is shown to be correct: the compound has similar affinity to the H2-receptor as has LSD. The affinities of D-LSD and BrLSD for the H2-receptor are compared with their affinities for other receptors. The pharmacology of D-LSD and BrLSD is reviewed. Evidence is assembled that BrLSD has considerable central effects."}
{"id": "PMID:30927", "title": "[Manipulated hyperacidification of autochthonous tumors].", "content": "Measurement on 3,4-benzopyrene- and methylcholanthrene-induced tumours of the rat (and mouse) showed that the multiple established manipulated hyperacidification of transplantation tumours to values about pH 6 is possible also on autochthonous tumours.", "contents": "[Manipulated hyperacidification of autochthonous tumors]. Measurement on 3,4-benzopyrene- and methylcholanthrene-induced tumours of the rat (and mouse) showed that the multiple established manipulated hyperacidification of transplantation tumours to values about pH 6 is possible also on autochthonous tumours."}
{"id": "PMID:30928", "title": "[Phylogenetic aspects of acquired immunity].", "content": "A review of literature on phylogenesis of acquired immunity shows an increasing activity and potential of this complex apparatus. This system is responsible for the immunosurveillance, i.e. the control and recognition of transformed cells. Obviously the functions and morphology of the immune competent apparatus become more active and specific with growing complexity of living conditions. Since organisms become the more vulnerable the higher stages of development are reached, the sense of this evolution lies in protecting these organisms against environmental influences and in allowing survival. Recognition and elimination of malignant cells is part of this capacity acquired by evolution.", "contents": "[Phylogenetic aspects of acquired immunity]. A review of literature on phylogenesis of acquired immunity shows an increasing activity and potential of this complex apparatus. This system is responsible for the immunosurveillance, i.e. the control and recognition of transformed cells. Obviously the functions and morphology of the immune competent apparatus become more active and specific with growing complexity of living conditions. Since organisms become the more vulnerable the higher stages of development are reached, the sense of this evolution lies in protecting these organisms against environmental influences and in allowing survival. Recognition and elimination of malignant cells is part of this capacity acquired by evolution."}
{"id": "PMID:30929", "title": "[The time lapse of the cytostatic effect of ifosfamide].", "content": "The time lapse of the effect of ifosfamid on the solid DS carcinosarcoma has been studied using 204 Wistar rats. The main results and the conclusions are as follows: 1. The transplantability of the tumor is abolished two hours after the i.v. application of 180 mg/kg isofamid (cessation of tumor cell proliferation). 2. Yet, the tumor tissue to be grafted is not damaged thoroughly by this treatment. It is possible that the still viable tumor cells were killed by the non-suppressed immune system of the recipients. 3. As determined by trypan blue dye exclusion and registration of glycolytic activity, the main part of tumor cells remains viable. As lately as 4 days after the therapy 80% of the cells incorporate trypan blue and the glycolytic activity is inhibited in the order of 80%. 4. It is to be expected that within two hours, a period sufficient for proliferation inhibition of tumor cells, only 30% of the active form of the drug administered can be found in the tumor. In this context the toxification (activation) kinetics of ifosfamid is discussed and an optimized, programmed infusion is considered. 5. The treatment with ifosfamid does not affect at least up to the third day the tumor hyperacidification attainable by a long-lasting glucose infusion.", "contents": "[The time lapse of the cytostatic effect of ifosfamide]. The time lapse of the effect of ifosfamid on the solid DS carcinosarcoma has been studied using 204 Wistar rats. The main results and the conclusions are as follows: 1. The transplantability of the tumor is abolished two hours after the i.v. application of 180 mg/kg isofamid (cessation of tumor cell proliferation). 2. Yet, the tumor tissue to be grafted is not damaged thoroughly by this treatment. It is possible that the still viable tumor cells were killed by the non-suppressed immune system of the recipients. 3. As determined by trypan blue dye exclusion and registration of glycolytic activity, the main part of tumor cells remains viable. As lately as 4 days after the therapy 80% of the cells incorporate trypan blue and the glycolytic activity is inhibited in the order of 80%. 4. It is to be expected that within two hours, a period sufficient for proliferation inhibition of tumor cells, only 30% of the active form of the drug administered can be found in the tumor. In this context the toxification (activation) kinetics of ifosfamid is discussed and an optimized, programmed infusion is considered. 5. The treatment with ifosfamid does not affect at least up to the third day the tumor hyperacidification attainable by a long-lasting glucose infusion."}
{"id": "PMID:30930", "title": "[Effect of different temperature fractions of RNA on allogenic inhibition of hematopoietic stem cells of mouse bone marrow and embryonal liver].", "content": "In the system of non-syngeneic transfer of stem hemopoietic cells, the preliminary incubation of the cells of bone marrow or embryonic liver of the C57BL mice with different temperature RNA fractions isolated from the spleen of (CBAXC57BL) F1 was shown to lead to the complete or partial restoration of the colony forming ability of the donor cells. The 63 degrees RNA fraction was shown to have the greatest restorative effect.", "contents": "[Effect of different temperature fractions of RNA on allogenic inhibition of hematopoietic stem cells of mouse bone marrow and embryonal liver]. In the system of non-syngeneic transfer of stem hemopoietic cells, the preliminary incubation of the cells of bone marrow or embryonic liver of the C57BL mice with different temperature RNA fractions isolated from the spleen of (CBAXC57BL) F1 was shown to lead to the complete or partial restoration of the colony forming ability of the donor cells. The 63 degrees RNA fraction was shown to have the greatest restorative effect."}
{"id": "PMID:30932", "title": "Effects of ovine hydatid cyst fluid in sheep before and after treatment with hydrocortisone, antihistamines and atropine.", "content": "The cardiovascular and respiratory responses to scolex-free ovine hydatid cyst fluid were studied in 65 sodium pentobarbital-anesthetized sheep. The arterial blood pressure (ABP), central venous pressure (CVP), stethogram and electrocardiogram were recorded. Intra-venous administration of 10 ml or less hydatid fluid brought about moderate to severe fall in ABP and rapid respiration or permanent respiratory cessation in majority of the animals. Forty six percent of the sheep died of circulatory and respiratory failure after the first injection or the hydatid fluid. Boiled hydatid fluid did not lose its potency to evoke the above responses. Hydrocortisone, given 200 mg daily for seven days, failed to prevent the reactions to hydatid fluid. Intravenous administration of the antihistamines chlorpheniramine, 4 mg/kg, and antazoline, 5 mg/kg, caused only partial prevention of the responses in 8 out of 15 responsive sheep. Pretreatment of the animals with atropine, 0.5--1 mg/kg subcutaneously, did not block the reactions. The cardiovascular and respiratory responses to ovine hydatid fluid may be due to antigen-antibody reactions or some toxic component of the fluid.", "contents": "Effects of ovine hydatid cyst fluid in sheep before and after treatment with hydrocortisone, antihistamines and atropine. The cardiovascular and respiratory responses to scolex-free ovine hydatid cyst fluid were studied in 65 sodium pentobarbital-anesthetized sheep. The arterial blood pressure (ABP), central venous pressure (CVP), stethogram and electrocardiogram were recorded. Intra-venous administration of 10 ml or less hydatid fluid brought about moderate to severe fall in ABP and rapid respiration or permanent respiratory cessation in majority of the animals. Forty six percent of the sheep died of circulatory and respiratory failure after the first injection or the hydatid fluid. Boiled hydatid fluid did not lose its potency to evoke the above responses. Hydrocortisone, given 200 mg daily for seven days, failed to prevent the reactions to hydatid fluid. Intravenous administration of the antihistamines chlorpheniramine, 4 mg/kg, and antazoline, 5 mg/kg, caused only partial prevention of the responses in 8 out of 15 responsive sheep. Pretreatment of the animals with atropine, 0.5--1 mg/kg subcutaneously, did not block the reactions. The cardiovascular and respiratory responses to ovine hydatid fluid may be due to antigen-antibody reactions or some toxic component of the fluid."}
{"id": "PMID:30936", "title": "Hypercarbia at birth: a possible role in the pathogenesis of intraventricular hemorrhage.", "content": "To test the hypothesis that birth asphyxia has a role in the etiology of intraventricular hemorrhage (IVH), blood was collected from the umbilical artery (UA) at birth in 28 premature infants of 26 to 29 weeks gestation and analyzed for hydrogen ion concentration [H+], PCO2, standard bicarbonate level, and lactic acid level. The infants were followed up throughout their nursery stay until a diagnosis of IVH could be made or excluded, either by autopsy or clinical findings. Infants with IVH had lower Apgar scores. There were no differences in UA [H+] or bicarbonate or lactic acid levels. However, infants with IVH had a significantly higher UA PCO2. Although the difference appeared relatively small, the increase in PCO2 during labor may have been relatively large. It is concluded that hypercarbia, possibly by increasing cerebral blood flow, may be one important factor in the genesis of IVH.", "contents": "Hypercarbia at birth: a possible role in the pathogenesis of intraventricular hemorrhage. To test the hypothesis that birth asphyxia has a role in the etiology of intraventricular hemorrhage (IVH), blood was collected from the umbilical artery (UA) at birth in 28 premature infants of 26 to 29 weeks gestation and analyzed for hydrogen ion concentration [H+], PCO2, standard bicarbonate level, and lactic acid level. The infants were followed up throughout their nursery stay until a diagnosis of IVH could be made or excluded, either by autopsy or clinical findings. Infants with IVH had lower Apgar scores. There were no differences in UA [H+] or bicarbonate or lactic acid levels. However, infants with IVH had a significantly higher UA PCO2. Although the difference appeared relatively small, the increase in PCO2 during labor may have been relatively large. It is concluded that hypercarbia, possibly by increasing cerebral blood flow, may be one important factor in the genesis of IVH."}
{"id": "PMID:30937", "title": "Serum gamma-glutamyl transpeptidase acitvity: a chemical determinant of alcohol consumption during adolescence.", "content": "The drinking habits of 55 adolescents, aged 12 to 22 years, were evaluated in light of the current presumed upsurge in adolescent alcohol use. SGPT, SGOT, and alkaline phosphatase concentrations were essentially normal in all subjects. Serum gamma-glutamyl transpeptidase (GGTP) concentrations were elevated in 12 of 15 adolescents who consumed six or more drinks per day. It is suggested that this test may warrant inclusion among other targeted screening procedures performed in teenage patients suspected of heavy alcohol consumption.", "contents": "Serum gamma-glutamyl transpeptidase acitvity: a chemical determinant of alcohol consumption during adolescence. The drinking habits of 55 adolescents, aged 12 to 22 years, were evaluated in light of the current presumed upsurge in adolescent alcohol use. SGPT, SGOT, and alkaline phosphatase concentrations were essentially normal in all subjects. Serum gamma-glutamyl transpeptidase (GGTP) concentrations were elevated in 12 of 15 adolescents who consumed six or more drinks per day. It is suggested that this test may warrant inclusion among other targeted screening procedures performed in teenage patients suspected of heavy alcohol consumption."}
{"id": "PMID:30933", "title": "Acid-base and oxidation-reduction relationships.", "content": "pH, the symbol for \"hydrogen-ion concentration\", is a series of dimensionless \"units\" that have only general significance. The author shows that, when considered on the basis of the relationship to oxidation-reduction, the relative significance of any pair of coordinates becomes more significant. However, the theoretical relationship as currently accepted by the Nernst equation, i.e. a shift of 59.1 milivolts for each shift of 1.0 pH, does not apply to macromolecular systems, such as in vivo. The author solved this difficulty by plotting the corrdinates graphically by bisecting pH relationships at 7.0 and oxidation-reduction relationships at Eh 0.0 milivolts, forming four quadrants. With this scheme the significance of any pair of coordinates can be readily recognized. The application of this method to biology and medicine is shown in the companion paper \"pH and Eh relationships in the body\".", "contents": "Acid-base and oxidation-reduction relationships. pH, the symbol for \"hydrogen-ion concentration\", is a series of dimensionless \"units\" that have only general significance. The author shows that, when considered on the basis of the relationship to oxidation-reduction, the relative significance of any pair of coordinates becomes more significant. However, the theoretical relationship as currently accepted by the Nernst equation, i.e. a shift of 59.1 milivolts for each shift of 1.0 pH, does not apply to macromolecular systems, such as in vivo. The author solved this difficulty by plotting the corrdinates graphically by bisecting pH relationships at 7.0 and oxidation-reduction relationships at Eh 0.0 milivolts, forming four quadrants. With this scheme the significance of any pair of coordinates can be readily recognized. The application of this method to biology and medicine is shown in the companion paper \"pH and Eh relationships in the body\"."}
{"id": "PMID:30934", "title": "pH and Eh relationships in the body.", "content": "This report concerns application of the graphical method for representing pH and Eh relationships in macromolecular systems (see previous paper) to in vivo studies. The author presents reasons for concluding that controlled measurements of urine are satisfactory indicators of changes in pH and Eh in the body whereas blood studies remain relatively constant. The original concept had to be modified because of two little known \"reversing phenomena\". One is well known to physicians as the \"acid rebound\" because of the acid reaction of urine when an excess of a base is administered. This is a paradox because it would be expected to be more alkaline. The second phenomenon occurs following hyperoxidation, such as in narcotic addiction, and results in reduction. Both hyperalkalinity and hyperoxidation result in an acid reaction. The author concludes that they are phases of a single phenomenon. It is the basis for \"Chapman's law\": Unfavorable effects on the body cause the urine pH and Eh to shift away from normal whereas favorable effects cause them to shift toward normal.", "contents": "pH and Eh relationships in the body. This report concerns application of the graphical method for representing pH and Eh relationships in macromolecular systems (see previous paper) to in vivo studies. The author presents reasons for concluding that controlled measurements of urine are satisfactory indicators of changes in pH and Eh in the body whereas blood studies remain relatively constant. The original concept had to be modified because of two little known \"reversing phenomena\". One is well known to physicians as the \"acid rebound\" because of the acid reaction of urine when an excess of a base is administered. This is a paradox because it would be expected to be more alkaline. The second phenomenon occurs following hyperoxidation, such as in narcotic addiction, and results in reduction. Both hyperalkalinity and hyperoxidation result in an acid reaction. The author concludes that they are phases of a single phenomenon. It is the basis for \"Chapman's law\": Unfavorable effects on the body cause the urine pH and Eh to shift away from normal whereas favorable effects cause them to shift toward normal."}
{"id": "PMID:30940", "title": "Rates of block by procaine and benzocaine and the procaine-benzocaine interaction at the node of Ranvier.", "content": "1. Action potentials and their maximum rates of rise, VA, were measured in single myelinated nerve fibres of the frog, Rana esculenta at room temperature. 2. On applying 1 mM procaine (pH 7.2) at 20 Hz stimulus frequency, half of the final VA reduction was reached at ton = 0.27 s; on applying 0.5 mM benzocaine (pH 7,2) at 50 HZ, ton was 0.12 s. Increasing the stimulus frequency between 2 and 50 HZ increased the rate of block by procaine but not by benzocaine. 3. Recovery in Ringer solution (pH 7.2) from 30-s treatment with 1 mM procaine (pH 7.2), the equieffective 0.15 mM procaine (pH 8.9) and from 0.5 mM benzocaine (pH 7.2) was 54%, 31% and 70%, respectively, within 1 s. 4. Changing between alkaline Ringer solution (pH 8.9) and 1 mM procaine (pH 7.2) led to transitory excessive block. Changing between 1 mM procaine (pH 7.2) and acid Ringer solution (pH 6.0) and washing out 10 mM procaine (pH 5.5) with neutral Ringer solution also led to a non-monotonic change in VA. 5. If hyperpolarizing pulses (30 ms, 20 mV) preceded the stimuli, changing the frequency of the pulse pairs led to a gradual moderate relief of block in procaine, turning off prepulses (at 10 HZ) to a gradual increase of block. In benzocaine changing from 1 to 10 HZ had no effect but turning off prepulses led to a prompt large increase of block. In procaine + benzocaine the membrane responded much as in benzocaine alone. At 1 HZ (prepulses) VA in 0.4 mM procaine was smaller than in 0.4 mM procaine + 0.3 mM benzocaine. 6. These phenomena can be explained on the assumption of voltage-dependent binding of benzocaine and procaine to a common receptor. The rate of block appears to be limited by access to the receptor, more in the case of benzocaine than of procaine.", "contents": "Rates of block by procaine and benzocaine and the procaine-benzocaine interaction at the node of Ranvier. 1. Action potentials and their maximum rates of rise, VA, were measured in single myelinated nerve fibres of the frog, Rana esculenta at room temperature. 2. On applying 1 mM procaine (pH 7.2) at 20 Hz stimulus frequency, half of the final VA reduction was reached at ton = 0.27 s; on applying 0.5 mM benzocaine (pH 7,2) at 50 HZ, ton was 0.12 s. Increasing the stimulus frequency between 2 and 50 HZ increased the rate of block by procaine but not by benzocaine. 3. Recovery in Ringer solution (pH 7.2) from 30-s treatment with 1 mM procaine (pH 7.2), the equieffective 0.15 mM procaine (pH 8.9) and from 0.5 mM benzocaine (pH 7.2) was 54%, 31% and 70%, respectively, within 1 s. 4. Changing between alkaline Ringer solution (pH 8.9) and 1 mM procaine (pH 7.2) led to transitory excessive block. Changing between 1 mM procaine (pH 7.2) and acid Ringer solution (pH 6.0) and washing out 10 mM procaine (pH 5.5) with neutral Ringer solution also led to a non-monotonic change in VA. 5. If hyperpolarizing pulses (30 ms, 20 mV) preceded the stimuli, changing the frequency of the pulse pairs led to a gradual moderate relief of block in procaine, turning off prepulses (at 10 HZ) to a gradual increase of block. In benzocaine changing from 1 to 10 HZ had no effect but turning off prepulses led to a prompt large increase of block. In procaine + benzocaine the membrane responded much as in benzocaine alone. At 1 HZ (prepulses) VA in 0.4 mM procaine was smaller than in 0.4 mM procaine + 0.3 mM benzocaine. 6. These phenomena can be explained on the assumption of voltage-dependent binding of benzocaine and procaine to a common receptor. The rate of block appears to be limited by access to the receptor, more in the case of benzocaine than of procaine."}
{"id": "PMID:30941", "title": "Chloride binding and the Bohr effect of human fetal erythrocytes and HbFII solutions.", "content": "1. We have observed that the alkaline Bohr effect of washed human fetal erythrocytes was larger than in human adult intact red cells, in physiological conditions of pH, PCO2 and temperature. This was also observed independently of the presence of CO2 and of 2,3 diphosphoglycerate (fresh or stored erythrocytes). 2. Experiments performed in purified HbFII and HbA1 solutions and direct titration of protons released upon oxygenation confirmed the larger alkaline Bohr effect of fetal hemoglobin, at physiological ionic strength. 3. At low chloride concentration HbFII solutions had an alkaline Bohr effect identical to that measured in HbA1 solutions. 4. Titration of purified Hb solutions with increasing concentrations of NaCl evidenced a lower O2 linked chloride binding by HbFII and predominantly at acid pH. 5. It is concluded that the larger alkaline Bohr effect of fetal erythrocytes of HbFII solutions is related to a diminished acid Bohr effect, due to the lower affinity of HbFII for chloride anions. 6. The physiological interest of these results for placental O2 transfer (double Bohr effect) and O2 delivery to the foetus is discussed.", "contents": "Chloride binding and the Bohr effect of human fetal erythrocytes and HbFII solutions. 1. We have observed that the alkaline Bohr effect of washed human fetal erythrocytes was larger than in human adult intact red cells, in physiological conditions of pH, PCO2 and temperature. This was also observed independently of the presence of CO2 and of 2,3 diphosphoglycerate (fresh or stored erythrocytes). 2. Experiments performed in purified HbFII and HbA1 solutions and direct titration of protons released upon oxygenation confirmed the larger alkaline Bohr effect of fetal hemoglobin, at physiological ionic strength. 3. At low chloride concentration HbFII solutions had an alkaline Bohr effect identical to that measured in HbA1 solutions. 4. Titration of purified Hb solutions with increasing concentrations of NaCl evidenced a lower O2 linked chloride binding by HbFII and predominantly at acid pH. 5. It is concluded that the larger alkaline Bohr effect of fetal erythrocytes of HbFII solutions is related to a diminished acid Bohr effect, due to the lower affinity of HbFII for chloride anions. 6. The physiological interest of these results for placental O2 transfer (double Bohr effect) and O2 delivery to the foetus is discussed."}